2010-02-10T00:30:44Z http://precedings.nature.com/oai2

oai:nature.com:10.1038/npre.2006.7.1 2006-11-16T09:47:49Z neuroscience

INCF -- new capability for global coordination in neuroinformatics 2006-11-16T12:26:11Z Jan G. Bjaalie Neuroscience The Global Science Forum (GSF) of the OECD has initiated a new international organization, INCF, to further the development of Neuroinformatics as a global effort with the support of all ministers of research within OECD. This presentation explains the background for the establishment of the INCF, outlines some of the goals, and defines the operations of the INCF Secretariat in relation the INCF National nodes and the general neuroscience community. http://precedings.nature.com/documents/7/version/1 oai:nature.com:10.1038/npre.2006.7.1 http://dx.doi.org/10.1038/npre.2006.7.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2006.8.1 2006-11-30T02:33:52Z biotechnology genetics pharmacology

PharmGKB: Capturing knowledge to catalyze pharmacogenomics research 2006-11-30T07:29:51Z Russ B. Altman Biotechnology Genetics & Genomics Pharmacology This is a powerpoint presentation made initially at the Cold Spring Harbor meeting on Pharmacogenomics, November 2006. It discusses the PharmGKB (http://www.pharmgkb.org/) and how we are building a pipeline for annotation of knowledge. In particular, we are focusing on pathway knowledge, "Very important Pharmacogene" annotations, and curation of the pharmacogenomics literature. We are building an ontology-based system to capture and aggregate knowledge, for use by our curators. http://precedings.nature.com/documents/8/version/1 oai:nature.com:10.1038/npre.2006.8.1 http://dx.doi.org/10.1038/npre.2006.8.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2006.9.1 2006-11-30T15:06:03Z neuroscience

DARPP-32 is a robust integrator of dopamine and glutamate signals 2006-11-30T13:14:53Z Nicolas Le Novere Eric Fernandez Renaud Schiappa Jean-Antoine Girault Neuroscience Integration of neurotransmitter and neuromodulator signals in the striatum plays a central role in the functions and dysfunctions of the basal ganglia. DARPP-32 is a key actor of this integration in the GABAergic medium-size spiny neurons, in particular in response to dopamine and glutamate. When phosphorylated by cAMP-dependent protein kinase (PKA) DARPP-32 inhibits protein phosphatase-1 (PP1), whereas when phosphorylated by cyclin-dependent kinase 5 (CDK5) it inhibits PKA. DARPP-32 is also regulated by casein kinases and by several protein phosphatases. These complex and intricate regulations make simple predictions of DARPP-32 dynamic behaviour virtually impossible. We used detailed quantitative modelling of the regulation of DARPP-32 phosphorylation to improve our understanding of its function. The models included all the combinations of the three best characterized phosphorylation sites of DARPP-32, their regulation by kinases and phosphatases, and the regulation of those enzymes by cAMP and Ca2+ signals. Dynamic simulations allowed to observe the temporal relationships between cAMP and Ca2+ signals. We confirmed that the proposed regulation of protein phosphatase-2A (PP2A) by calcium can account for the observed decrease of Threonine 75 phosphorylation upon glutamate receptor activation. Sensitivity analysis showed that CDK5 activity is a major regulator of the response, as previously suggested. Conversely, the regulation of PP2A by PKA or by calcium, had little effect on the function of DARPP-32 in these conditions. The simulations showed that DARPP-32 is not only a robust signal integrator, but also a coincidence detector, the delay between cAMP and calcium signals affecting the response to the latter. This integration did not depend on the concentration of DARPP-32, while the absolute response on PP1 varied linearly. In silico mutants showed that Ser137 phosphorylation affects the coincidence detector function, and that constitutive phosphorylation in Ser137 transforms DARPP-32 in a quasi-irreversible switch. This work is a first attempt to better understand the complex interactions between cAMP and Ca2+ regulation of DARPP-32. Progressive inclusion of additional components should lead to a realistic model of signalling networks underlying the function of striatal neurons. http://precedings.nature.com/documents/9/version/1 oai:nature.com:10.1038/npre.2006.9.1 http://dx.doi.org/10.1038/npre.2006.9.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2006.10.1 2006-11-30T15:13:38Z biotechnology

Open Standards and Resources in Systems Biology: collaborative scale-up toward virtual life 2006-11-30T13:26:02Z Nicolas Le Novere Biotechnology The practise of Systems Biology relies on interfaces. Interfaces
between the entities we study: the paradigm moved from a physical
object centric view toward a relationship-centric one; interfaces
between tools: From the retrieval of the primary data to the fine
analysis of a model's behaviour, one uses many tools, more or less
well connected; interfaces between individuals: To build any
non-trivial mechanistic model requires to merge existing work and
gather external expertise.

If we want these interfaces to be generic enough to allow for anybody
to leverage on existing toolkits, a fundamental requirement is the
existence of community-developed well supported standards, but also
open resources where to find the "lego" blocks. Over the last
half-decade, several efforts have been launched in that direction,
whether concerning encoding format, ontologies or databases. Some of
them are now well-established in the field and play a significant role
to improve its coherence but also to increase the size and the quality
of quantitative models.
 http://precedings.nature.com/documents/10/version/1 oai:nature.com:10.1038/npre.2006.10.1 http://dx.doi.org/10.1038/npre.2006.10.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.11.1 2007-01-16T04:50:15Z chemistry molecular-cell-biology bioinformatics

Consortium for Functional Glycomics Overview 2007-01-15T21:06:22Z James C. Paulson Chemistry Molecular Cell Biology Bioinformatics This presentation provides an overview of the Consortium for Functional Glycomics. http://precedings.nature.com/documents/11/version/1 oai:nature.com:10.1038/npre.2007.11.1 http://dx.doi.org/10.1038/npre.2007.11.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.12.1 2007-01-16T04:56:05Z chemistry molecular-cell-biology bioinformatics

Developments in CFG glycan and pathogen polysaccharide arrays 2007-01-15T21:14:31Z Ola Blixt Chemistry Molecular Cell Biology Bioinformatics This presentation summarizes developments in glycan and pathogen polysaccharide arrays at the Consortium for Functional Glycomics (CFG). http://precedings.nature.com/documents/12/version/1 oai:nature.com:10.1038/npre.2007.12.1 http://dx.doi.org/10.1038/npre.2007.12.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.15.1 2007-01-18T05:24:57Z molecular-cell-biology bioinformatics

Bioinformatics Approach for Functional Glycomics 2007-01-18T05:55:42Z James C. Paulson Molecular Cell Biology Bioinformatics Presentation in the Human Glycomics Proteomics Disease Initiative (HGPI) session. http://precedings.nature.com/documents/15/version/1 oai:nature.com:10.1038/npre.2007.15.1 http://dx.doi.org/10.1038/npre.2007.15.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.16.1 2007-01-19T13:33:36Z ecology bioinformatics evolutionary-biology

Comparative genomics and disorder prediction identify biologically relevant SH3 protein interactions 2007-01-19T11:36:08Z Pedro Beltrao Luis Serrano Ecology Bioinformatics Evolutionary Biology Protein interaction networks are an important part of the post-genomic effort to integrate a part-list view of the cell into system-level understanding. Using a set of 11 yeast genomes we show that combining comparative genomics and secondary structure information greatly increases consensus-based prediction of SH3 targets. Benchmarking of our method against positive and negative standards gave 83% accuracy with 26% coverage. The concept of an optimal divergence time for effective comparative genomics studies was analyzed, demonstrating that genomes of species that diverged very recently from _Saccharomyces cerevisiae_ (_S. mikatae_, _S. bayanus_, and _S. paradoxus_), or a long time ago (_Neurospora crassa_ and _Schizosaccharomyces pombe_), contain less information for accurate prediction of SH3 targets than species within the optimal divergence time proposed. We also show here that intrinsically disordered SH3 domain targets are more probable sites of interaction than equivalent sites within ordered regions. Our findings highlight several novel S. cerevisiae SH3 protein interactions, the value of selection of optimal divergence times in comparative genomics studies, and the importance of intrinsic disorder for protein interactions. Based on our results we propose novel roles for the _S. cerevisiae_ proteins Abp1p in endocytosis and Hse1p in endosome protein sorting. http://precedings.nature.com/documents/16/version/1 oai:nature.com:10.1038/npre.2007.16.1 http://dx.doi.org/10.1038/npre.2007.16.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.17.1 2007-01-20T16:41:38Z ecology earth-and-environment

Declarative modelling in the ecological and environmental sciences 2007-01-19T23:15:30Z Robert Muetzelfeldt Ecology Earth & Environment Most simulation models in ecological and environmental research are implemented as computer programs in a conventional programming language. This brief paper argues for a radically different approach, based on the representation of the model structure, relationships and equations in a declarative format (e.g. XML). Simulation code can then be generated from this, but in addition the model can be displayed and processed in a wide range of useful ways, greatly increasing the efficiency and effectiveness of the modelling process. http://precedings.nature.com/documents/17/version/1 oai:nature.com:10.1038/npre.2007.17.1 http://dx.doi.org/10.1038/npre.2007.17.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.18.1 2007-01-20T16:47:42Z ecology bioinformatics earth-and-environment

Environmental modelling and Web 2.0 - using Connotea to share XML-represented information 2007-01-20T14:42:59Z Robert Muetzelfeldt Ecology Bioinformatics Earth & Environment Much academic information can be represented in a structured way and published on the web as XML documents. Such information can then be displayed in a wide variety of ways, using different XSLT stylesheets. 

This presentation presents MultiGuise, a Web application which allows any of several XML documents to be displayed using any of several stylesheets. Both the documents and the stylesheets are bookmarked in Connotea, from where MultiGuise retrieves them using a special tag. This approach means that anyone can add documents and stylesheets, simply by bookmarking them in Connotea.

The approach is illustrated primarily with environmental models represented in XML, but also with examples from SBML (Systems Biology Markup Language) and philosophical arguments marked up in XML. http://precedings.nature.com/documents/18/version/1 oai:nature.com:10.1038/npre.2007.18.1 http://dx.doi.org/10.1038/npre.2007.18.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.19.1 2007-01-22T01:48:17Z biotechnology bioinformatics

The Systems Biology Markup Language (SBML) Level 2 Version 2 2007-01-22T04:01:51Z Michael Hucka Sarah M. Keating Biotechnology Bioinformatics The Systems Biology Markup Language (SBML) is a machine-readable model representation language for software tools in computational systems biology. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. SBML is by no means a perfect format, but it has achieved widespread acceptance as a de facto standard. It is supported worldwide by over 100 software systems (both open-source and commercial). The broad acceptance of a common, open format for exchanging models between software tools is a crucial step towards wider use of quantitative modeling in biology, because it allows researchers to build upon each other's work with greater ease and accuracy.

SBML can encode models consisting of biochemical entities (species) linked by reactions to form networks. An important principle is that models are decomposed into explicitly-labeled constituent elements, the set of which resembles a verbose rendition of chemical reaction equations. The representation deliberately does not cast the model directly into a set of differential equations or other specific interpretation of the model. The formalisms in SBML allows a wide range of biological phenomena to be modeled, including metabolism, cell signaling, gene regulation, and more. Significant flexibility and power comes from the ability to define arbitrary formulae for the rates of change of variables as well as the ability to express other constraints mathematically.

This tutorial covered the latest edition of SBML, which is Level 2 Version 2, finalized in September 2006. Topics covered include the basic common principles in SBML as well the changes introduced in Level 2 Version 2. We also discussed software tools for programmers, in particular libSBML. http://precedings.nature.com/documents/19/version/1 oai:nature.com:10.1038/npre.2007.19.1 http://dx.doi.org/10.1038/npre.2007.19.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.20.1 2007-01-22T01:50:17Z biotechnology bioinformatics

Evolving standards and infrastructure for systems biology: SBML, SBGN, and BioModels.net 2007-01-22T04:29:35Z Michael Hucka Biotechnology Bioinformatics Systems biology has arisen through the convergence of theoretical, computational, and mathematical modeling of systems and the need to understand the wealth of information being rapidly generated in biology. Systems biology by its nature requires collaborations between scientists with expertise in biology, chemistry, computer sciences, engineering, mathematics, and physics. Successful integration of these disciplines depends on bringing to bear both social and technological tools: namely, consortia that help forge collaborations and common understanding, software tools that permit analysis of vast and complex data, and agreed-upon standards that enable researchers to communicate and reuse each other's results in practical and unambiguous ways. In this presentation, I will discuss several international projects (SBML, SBGN, and BioModels.net) aimed at addressing the last issue.

An important prerequisite for effective sharing of computational models is reaching agreement on how to communicate them, both between software and between humans. The Systems Biology Markup Language (SBML) project is an effort to create a machine-readable format for representing computational models at the biochemical reaction level. By supporting SBML as an input and output format, different software tools can operate on the same representation of a model, removing chance for errors in translation and assuring a common starting point for analyses and simulations. SBML has become the most successful effort in this direction so far, with nearly 100 software tools supporting it today.

A recently-created sister project is the Systems Biology Graphical Notation (SBGN) project. It addresses the issue of consistent human communication, by attempting to add more rigor and consistency to the graphical network diagrams that often accompany published research on models of biological reaction systems. The real payoff will come when more people and software adopt such a common visual notation and it becomes as familiar to them as circuit schematics are to electronics engineers.

Finally, when developing and publishing computational models, it is only natural to want to put them into a database. The BioModels.net project is an effort to (1) provide a free, centralized, publicly-accessible database of human-curated computational models in SBML and other structured formats; (2) define agreed-upon standards for model curation; and (2) define agreed-upon vocabularies for annotating models with connections to biological data resources. http://precedings.nature.com/documents/20/version/1 oai:nature.com:10.1038/npre.2007.20.1 http://dx.doi.org/10.1038/npre.2007.20.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.21.1 2007-01-22T01:52:11Z biotechnology bioinformatics

The Systems Biology Markup Language (SBML): Where It's Been and Where It's Going 2007-01-22T04:39:05Z Michael Hucka Biotechnology Bioinformatics A cornerstone of systems biology is the use of computational modeling, by which hypotheses can be cast into a quantitative form that can be tested systematically. The use of computational modeling by biologists promises to pave the way for more rigorous analyses of biological functions, and ultimately will lead to new and better treatments for disease.

A crucial enabler for more widespread use of computational modeling in biology is reaching agreement on how to represent, store, and communicate models between software tools. The Systems Biology Markup Language (SBML) project is an effort to create a machine-readable format for representing computational models in biology. By supporting SBML as an input and output format, different software tools can operate on the same representation of a model, removing chances for errors in translation and assuring a common starting point for analyses and simulations. SBML has become the most successful effort in this direction so far, with over 100 software systems supporting it today.

In this presentation, I will discuss the current state of SBML, including recent developments such as this year's finalization of Version 2 of SBML Level 2. I will also survey some of the software tools that support SBML, and related projects that have arisen to support more effective use of computational models. Lastly, I will discuss expected future developments in SBML.
 http://precedings.nature.com/documents/21/version/1 oai:nature.com:10.1038/npre.2007.21.1 http://dx.doi.org/10.1038/npre.2007.21.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.22.1 2007-01-22T16:50:37Z bioinformatics evolutionary-biology

The likelihood that two proteins interact might depend on the proteins' age 2007-01-22T19:19:46Z Pedro Beltrao Bioinformatics Evolutionary Biology It has been previously shown [1] that _S. cerevisiae_ proteins preferentially interact with proteins of the same estimated likely time of origin. To study this observation further, the protein interaction networks of _S. cerevisiae_ and _H. sapiens_ were analyzed taking into account an estimate for the age of the proteins in these species. These estimates were obtained by studying the presence and absence of putative orthologs in other eukaryotic species. In this work preliminary results are described that point to a dependence of the likelihood of protein interaction on the proteins’ age. The probability of two proteins interactions was found to be linearly dependent on the time the proteins have co-existed in the species. http://precedings.nature.com/documents/22/version/1 oai:nature.com:10.1038/npre.2007.22.1 http://dx.doi.org/10.1038/npre.2007.22.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.23.1 2007-01-23T04:01:48Z bioinformatics

LipidMaps Core Update 2007-01-23T05:57:32Z Shankar Subramaniam Eoin Fahy Bioinformatics LipidMaps (http://www.lipidmaps.org) is a multidisciplinary project involving multiple institutions. The goal of this project is to identify lipid metabolites and reconstruct pathways associated with lipids in mammalian cells using quantitative measurements of lipids in macrophage cells. http://precedings.nature.com/documents/23/version/1 oai:nature.com:10.1038/npre.2007.23.1 http://dx.doi.org/10.1038/npre.2007.23.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.24.1 2007-01-23T13:01:12Z molecular-cell-biology neuroscience pharmacology bioinformatics

Dynamic Topology of Biological Networks 2007-01-23T16:48:13Z Ravi Iyengar Molecular Cell Biology Neuroscience Pharmacology Bioinformatics The mammalian cell can be represented as a large modular network that consists of a central signal network that interacts with and regulates multiple cellular machines that are responsible for phenotypic behavior. We have used graph-theory approaches to analyze signal flow through a network representing the hippocampal neuron and find that signal-induced connectivity results in the formation of many regulatory motifs. Information flow through the central signaling network is initiated by extra-cellular signals such as hormones binding to their receptors. The flow of information through the signaling network results in the appearance of regulatory motifs such as feedback loops, feedforward and bifan motifs. Within the large cellular networks, these regulatory motifs are juxtaposed next to each other in several formats such as the stacked configuration or the nested configuration. We have studied the dynamics of regulatory motifs by biochemical computation using ordinary differential equation models. Positive feedback loops can function as bistable switches. Nested feed-forward motifs can give rise to two emergent properties: coincidence detection and prolonged outputs for short inputs. Bifan motifs can control response times, with some configurations working as delays and others promoting rapid responses. Bifan motifs can also act as filters. Feed-forward motifs lead to signal prolongation and thus function as a switch to alter cell state. The functional consequences of organization of motifs within networks as well as the properties of feedback, feedforward and bifans motifs are presented. http://precedings.nature.com/documents/24/version/1 oai:nature.com:10.1038/npre.2007.24.1 http://dx.doi.org/10.1038/npre.2007.24.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.25.1 2007-01-23T16:58:17Z molecular-cell-biology bioinformatics

Intracellular Regulatory Networks are close to Monotone Systems 2007-01-23T16:57:11Z Avi Ma'ayan Ravi Iyengar Eduardo D. Sontag Molecular Cell Biology Bioinformatics Several meso-scale biological intracellular regulatory networks that have specified directionality of interactions have been recently assembled from experimental literature. Directed networks where links are characterized as positive or negative can be converted to systems of differential equations and analyzed as dynamical systems. Such analyses have shown that networks containing only sign-consistent loops, such as positive feed-forward and feedback loops function as monotone systems that display well-ordered behavior. Perturbations to monotone systems have unambiguous global effects and a predictability characteristic that confers advantages for robustness and adaptability. We find that three intracellular regulatory networks: bacterial and yeast transcriptional networks and a mammalian signaling network contain far more sign-consistent feedback and feed-forward loops than expected for shuffled networks. Inconsistent loops with negative links can be more easily removed from real regulatory networks as compared to shuffled networks. This topological feature in real networks emerges from the presence of hubs that are enriched for either negative or positive links, and is not due to a preference for double negative links in paths. These observations indicate that intracellular regulatory networks may be close to monotone systems and that this network topology contributes to the dynamic stability. http://precedings.nature.com/documents/25/version/1 oai:nature.com:10101/npre.2007.25.1 http://hdl.handle.net/10101/npre.2007.25.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.26.1 2007-03-02T11:42:42Z bioinformatics evolutionary-biology

Specificity and Evolvability in Eukaryotic Protein Interaction Networks 2007-02-28T20:11:50Z Pedro Beltrao Bioinformatics Evolutionary Biology Progress in uncovering the protein interaction networks of several species has led to questions of what underlying principles might govern their organization. Few studies have tried to determine the impact of protein interaction network evolution on the observed physiological differences between species. Using comparative genomics and structural information, we show here that eukaryotic species have rewired their interactomes at a fast rate of approximately 10?5 interactions changed per protein pair, per million years of divergence. For Homo sapiens this corresponds to 103 interactions changed per million years. Additionally we find that the specificity of binding strongly determines the interaction turnover and that different biological processes show significantly different link dynamics. In particular, human proteins involved in immune response, transport, and establishment of localization show signs of positive selection for change of interactions. Our analysis suggests that a small degree of molecular divergence can give rise to important changes at the network level. We propose that the power law distribution observed in protein interaction networks could be partly explained by the cell's requirement for different degrees of protein binding specificity. http://precedings.nature.com/documents/26/version/1 oai:nature.com:10.1038/npre.2007.26.1 http://dx.doi.org/10.1038/npre.2007.26.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.35.1 2007-06-07T11:14:46Z biotechnology molecular-cell-biology bioinformatics

Genes2Networks: Connecting Lists of Proteins by Using Background Literature-based Mammalian Networks 2007-06-07T14:00:03Z Avi Ma'ayan Biotechnology Molecular Cell Biology Bioinformatics In recent years, in-silico literature-based mammalian protein-protein interaction network datasets have been developed. These datasets contain binary interactions extracted manually from legacy experimental biomedical research literature. Placing lists of genes or proteins identified as significantly changing in multivariate experiments, in the context of background knowledge about binary interactions, can be used to place these genes or proteins in the context of pathways and protein complexes.
Genes2Networks is a software system that integrates the content of ten mammalian literature-based interaction network datasets. Filtering to prune low-confidence interactions was implemented. Genes2Networks is delivered as a web-based service using AJAX. The system can be used to extract relevant subnetworks created from “seed” lists of human Entrez gene names. The output includes a dynamic linkable three color web-based network map, with a statistical analysis report that identifies significant intermediate nodes used to connect the seed list. Genes2Networks is available at http://actin.pharm.mssm.edu/genes2networks.
Genes2Network is a powerful web-based software application tool that can help experimental biologists to interpret high-throughput experimental results used in genomics and proteomics studies where the output of these experiments is a list of significantly changing genes or proteins. The system can be used to find relationships between nodes from the seed list, and predict novel nodes that play a key role in a common function. http://precedings.nature.com/documents/35/version/1 oai:nature.com:10101/npre.2007.35.1 http://hdl.handle.net/10101/npre.2007.35.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.35.2 2007-06-08T11:29:03Z biotechnology molecular-cell-biology bioinformatics

Genes2Networks: Connecting Lists of Proteins by Using Background Literature-based Mammalian Networks 2007-06-07T15:27:51Z Jeremy I. Posner Seth Berger Avi M. Ma'ayan Biotechnology Molecular Cell Biology Bioinformatics In recent years, in-silico literature-based mammalian protein-protein interaction network datasets have been developed. These datasets contain binary interactions extracted manually from legacy experimental biomedical research literature. Placing lists of genes or proteins identified as significantly changing in multivariate experiments, in the context of background knowledge about binary interactions, can be used to place these genes or proteins in the context of pathways and protein complexes.
Genes2Networks is a software system that integrates the content of ten mammalian literature-based interaction network datasets. Filtering to prune low-confidence interactions was implemented. Genes2Networks is delivered as a web-based service using AJAX. The system can be used to extract relevant subnetworks created from “seed” lists of human Entrez gene names. The output includes a dynamic linkable three color web-based network map, with a statistical analysis report that identifies significant intermediate nodes used to connect the seed list. Genes2Networks is available at http://actin.pharm.mssm.edu/genes2networks.
Genes2Network is a powerful web-based software application tool that can help experimental biologists to interpret high-throughput experimental results used in genomics and proteomics studies where the output of these experiments is a list of significantly changing genes or proteins. The system can be used to find relationships between nodes from the seed list, and predict novel nodes that play a key role in a common function. http://precedings.nature.com/documents/35/version/2 oai:nature.com:10101/npre.2007.35.2 http://hdl.handle.net/10101/npre.2007.35.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.39.1 2007-06-12T09:47:27Z chemistry

Open Notebook Science Using Blogs and Wikis 2007-06-11T20:23:09Z Jean-Claude Bradley Chemistry The first half is a summary of how the Bradley group at Drexel University is doing Open Notebook Science with the UsefulChem project to synthesize and test novel anti-malarial compounds. Graduate student Dave Strumfels' code to compute kinetics from JCAMP NMR reaction profiles is then highlighted. Finally screenshots are shown of a building on Nature Island in Second Life where Beth Ritter-Guth and Eloise Pasteur have helped to set up a poster room with NMR spectra, molecules and an organic chemistry quiz that can be activated by clicking on an obelisk. 
 http://precedings.nature.com/documents/39/version/1 oai:nature.com:10.1038/npre.2007.39.1 http://dx.doi.org/10.1038/npre.2007.39.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.44.1 2007-06-13T06:40:32Z molecular-cell-biology

Intact mitochondria migrate in membrane tubular network connections formed between human stem cells 2007-06-12T16:02:02Z Attila Csordas Attila Cselenyák Ferenc Uher Marianna Murányi Simone Hennerbichler Heinz Redl Márk Kollai Zsombor Lacza Molecular Cell Biology The hypothesis of mitochondrial transfer between eukaryotic animal cells is intriguing, although its route of action and physiological role is unknown. Our goal was to examine intercellular connections among several types of stem cells and to observe whether intact functional mitochondria may travel via these connections. Time-lapse laser scanning confocal microscopy has shown that human amnion-derived stem cells as well as bone marrow derived mouse and human mesenchymal stem cells form cell-to-cell connections via a tubular membrane network. The maximal length of these micrometer-thick tubes is around 180 ?m. Interestingly, freshly isolated amniotic epithelial stem cells did not form these connections, only after several passages when the morphology of the cells is significantly altered. Large area cell-cell contacts can be retained as long thin membrane bridges after the cells depart and de novo tube formation is also observed. Using MitoTracker red staining we observed that intact mitochondria are moving in these tubes by 20 – 60 nm/s velocity, suggesting that mitochondria can leave one cell via the membrane tubes and can enter into another cell. These results suggest that specific types of stem cells form comprehensive tubular networks among each other. One physiological role of these networks may be that mitochondria can migrate from one cell to the other, which may be a novel way of communication among stem cells. http://precedings.nature.com/documents/44/version/1 oai:nature.com:10.1038/npre.2007.44.1 http://dx.doi.org/10.1038/npre.2007.44.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.48.1 2007-06-14T05:22:34Z ecology

Noise, cycles, and noisy cycles in finite populations 2007-06-13T13:45:58Z Mario Pineda-Krch Ecology Periodic predator-prey dynamics in constant environments are usually taken as indicative of deterministic limit cycles. It is known, however, that demographic stochasticity in finite populations can also give rise to regular population cycles, even when the corresponding deterministic models predict a stable equilibrium. The existence of quasi-cycles substantially expands the scope for natural patterns of periodic population oscillations caused by ecological interactions, thereby complicating the conclusive interpretation of such patterns. It is, however, feasible and straightforward to accurately distinguish between the two types of cycle through the combined analysis of autocorrelations and marginal distributions of population sizes. By confronting these results with real ecological time series even short and imperfect time series allow quasi-cycles and limit cycles to be distinguished reliably.

This work has been published in:
Pineda-Krch M, Blok HJ, Dieckmann U, Doebeli M. 2007. A tale of two cycles - Distinguishing between true limit cycles and quasi-cycles in finite predator-prey populations. Oikos 116: 53-64. http://precedings.nature.com/documents/48/version/1 oai:nature.com:10.1038/npre.2007.48.1 http://dx.doi.org/10.1038/npre.2007.48.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.50.1 2007-06-14T13:14:29Z chemistry bioinformatics

Fast and Scriptable Molecular Graphics in Web Browsers without Java3D 2007-06-14T14:09:18Z Egon Willighagen Miguel Howard Chemistry Bioinformatics Jmol is a free, open source molecule viewer for chemistry and biochemistry. It is cross-platform, running on Windows, Mac OS X, and Linux/Unix systems. The software consists of three parts: the JmolApplet is a web browser applet that can be integrated into web pages; the Jmol application is a standalone Java application that runs on the desktop; and the JmolViewer is a development tool kit that can be integrated into other Java applications. http://precedings.nature.com/documents/50/version/1 oai:nature.com:10.1038/npre.2007.50.1 http://dx.doi.org/10.1038/npre.2007.50.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.52.1 2007-06-15T15:05:40Z biotechnology cancer immunology pharmacology bioinformatics

Molecular Static and Dynamic Analyses reveal Flaw in Murine Model used by US FDA to Detect Drug Carcinogenicity 2007-06-15T18:05:48Z Trevor Marshall Biotechnology Cancer Immunology Pharmacology Bioinformatics The US FDA currently accepts carcinogenicity studies of pharmaceutical drugs based on murine models. In addition to 6 month studies with p53(+/-) and ras.H2 transgenic mice, lifetime studies (typically 2 years) in WT mice or rats are also considered as evidence that a drug lacks carcinogenic activity. This model is not always exhaustive. For example, during the acceptance testing of the ARB Olmesartan[1], possible carcinogenicity observed in hamsters was not able to be duplicated in rats, or in transgenic mice. We have previously used the static molecular modeling of AutoDock to demonstrate that Olmesartan has agonostic activity in the PDB:1DB1 model of the human VDR Nuclear Receptor[2], while it has antagonistic activity in the PDB:1RK3 model of the rat VDR. This agonism has now been confirmed with Molecular Dynamics, using GROMACS. The murine VDR indeed lost its ability to bind the DRIP-205 co-activator when Olmesartan was the ligand, while the human VDR was activated by Olmesartan similarly to its native ligand (1,25-dihydroxyvitamin-D). Since the VDR is believed to express 913 genes[3], many of which are known to be associated with cancer pathogenesis, good homology between human VDR, and the animal model VDR, is exceedingly important. CONCLUSION: The murine environment is inadequate to accurately model drug carcinogenic activity in humans. A species should be chosen which has a VDR LBP homology closer to that of man. AutoDock and GROMACS molecular analyses are useful in resolving any remaining anomalies in the observed data.

References:
1. FDA CDER: NDA-21-286, Sankyo Pharma Inc Available from URL http://www.fda.gov/cder/foi/nda/2002/21-286_Benicar.htm
2. Marshall TG: VDR Nuclear Receptor Competence is the Key to Recovery from Chronic Inflammatory and Autoimmune Disease. Abstract presentation, DMM2006.
Available from URL http://AutoimmunityResearch.org/karolinska-handout.pdf
3. Wang TT, et al: Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin-D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
 http://precedings.nature.com/documents/52/version/1 oai:nature.com:10.1038/npre.2007.52.1 http://dx.doi.org/10.1038/npre.2007.52.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.56.1 2007-06-16T10:03:20Z ecology

Fluctuating population dynamics promotes the evolution of phenotypic plasticity 2007-06-16T13:37:56Z Mario Pineda-Krch Richard Svanbäck Michael Doebeli Ecology An increasing number of studies are showing evidence in support of sympatric speciation. One basic question remains, however. When a population has undergone a branching in its phenotype, is this due to an evolutionary branching in the underlying genotype or due to phenotypic plasticity modifying a single genotype? Thus, phenotypic plasticity has come to be viewed as a trait subject to selection, just like any other phenotypic character1,2. Here we present a model addressing the conditions under which a predator phenotype experiencing selection for two alternative optimal phenotypes gives rise to genetically based phenotypic branching or to phenotypic plasticity, allowing the corresponding genotype to give rise to two alternative, well-adapted phenotypes.
 http://precedings.nature.com/documents/56/version/1 oai:nature.com:10.1038/npre.2007.56.1 http://dx.doi.org/10.1038/npre.2007.56.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.57.1 2007-06-18T03:57:37Z ecology evolutionary-biology

Adaptive evolution and then what? 2007-06-16T13:48:47Z Richard Svanbäck Mario Pineda-Krch Michael Doebeli Ecology Evolutionary Biology Traits determining ecological interactions and dynamics are generally subject to natural selection. That genetically based individual variation in ecological traits can influence population dynamics has interested population biologist from various perspectives. Population ecologists recognized the need to incorporate individual variation in models of population regulation, while evolutionary biologists wish to understand genetic and evolutionary dynamics, e.g. of life history traits, in density-regulated populations. But how does adaptation in ecological traits affect population dynamics? In this project we investigated how ecological dynamics changes as a consequence of adaptive evolution in ecological traits using an individual-based predator-prey model. http://precedings.nature.com/documents/57/version/1 oai:nature.com:10.1038/npre.2007.57.1 http://dx.doi.org/10.1038/npre.2007.57.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.58.1 2007-06-18T08:52:34Z bioinformatics

Systems Biology Markup Language (SBML) Level 2: Structures and Facilities for Model Definitions 2007-06-18T09:21:05Z Michael Hucka Andrew M. Finney Stefan Hoops Sarah M. Keating Nicolas Le Novere Bioinformatics Not applicable http://precedings.nature.com/documents/58/version/1 oai:nature.com:10101/npre.2007.58.1 http://hdl.handle.net/10101/npre.2007.58.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.61.1 2007-06-18T12:20:14Z neuroscience

Reading the Neural Code: What do Spikes Mean for Behavior? 2007-06-18T15:10:47Z Dorian Aur Mandar Jog Neuroscience The present study reveals the existence of an intrinsic spatial code within neuronal spikes that predicts behavior. As rats learnt a T-maze procedural task, simultaneous changes in temporal occurrence of spikes and spike directivity are evidenced in “expert” neurons. While the number of spikes between the tone delivery and the beginning of turn phase reduced with learning, the generated spikes between these two events acquired behavioral meaning that is of highest value for action selection. Spike directivity is thus a hidden feature that reveals the semantics of each spike and in the current experiment, predicts the correct turn that the animal would subsequently make to obtain reward. Semantic representation of behavior can then be revealed as modulations in spike directivity during the time. This predictability of observed behavior based on subtle changes in spike directivity represents an important step towards reading and understanding the underlying neural code. http://precedings.nature.com/documents/61/version/1 oai:nature.com:10.1038/npre.2007.61.1 http://dx.doi.org/10.1038/npre.2007.61.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.62.1 2007-06-18T12:31:11Z biotechnology molecular-cell-biology bioinformatics

A Three dimesional stochastic spatio-temporal model of cell spreading 2007-06-18T16:00:58Z Yuguang P. Xiong Padmini Rangamani Benjamin Dubin-Thaler Michael Sheetz Ravi Iyengar Biotechnology Molecular Cell Biology Bioinformatics Cell motility is important for many physiological processes and the underlying
biochemical reactions motility have been well-characterized. Mathematical models, using
the biochemical reactions and focused on different types of spreading behavior have been
constructed and analyzed. In this study, we build on these previous models to develop a
three-dimensional stochastic model of isotropic spreading of mammalian fibroblasts. The model is composed of three actin remodeling reactions that occur stochastically in space and time and are regulated by membrane resistance forces. Numerical simulations indicate that the model qualitatively captures the experimentally observed isotropic cell spreading behavior. We analyzed the effects of varying branching reaction rates, membrane resistance forces and capping protein concentrations on the dynamics of isotropic spreading. The simulations allowed us to identify the range within which branching reaction rates and membrane force values cooperate to yield isotropic spreading behavior. The model predicts increasing capping protein concentration would lead to a linear decrease in average peripheral velocity. We tested this prediction experimentally using varying concentrations of a pharmacologic agent (Cytochalasin D)that caps growing actin filaments. We find that the experimental results agree with the numerical simulations. Thus, a spatio-temporally complex model made up of a simple set of stochastic reactions near the cell surface, when constrained by membrane forces, can yield deterministic behavior as characterized by isotropic cell spreading. http://precedings.nature.com/documents/62/version/1 oai:nature.com:10101/npre.2007.62.1 http://hdl.handle.net/10101/npre.2007.62.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.69.1 2007-07-13T13:33:27Z genetics bioinformatics evolutionary-biology

Promoter regions of many neural- and nutrition-related genes have experienced positive selection during human evolution 2007-06-18T21:04:29Z Ralph Haygood Olivier Fedrigo Brian Hanson Ken-Daigoro Yokoyama Gregory Wray Genetics & Genomics Bioinformatics Evolutionary Biology Surveys of protein-coding sequences for evidence of positive selection in humans and chimpanzees have flagged surprisingly few genes known to be involved in neural or nutritional processes, despite the pronounced differences between humans and chimpanzees in behavior, cognition, and diet. It may be that most such differences are due to changes in gene regulation rather than protein structure. Here, we present the first survey of promoter (5'-flanking) regions, which are rich in _cis_-regulatory sequences, for signatures of positive selection in humans. Our results indicate that positive selection has targeted the regulation of many genes known to be involved in neural development and function, both in the brain and elsewhere in the nervous system, and in nutrition, particularly glucose metabolism. http://precedings.nature.com/documents/69/version/1 oai:nature.com:10.1038/npre.2007.69.1 http://dx.doi.org/10.1038/npre.2007.69.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.100.1 2007-06-20T07:03:36Z cancer molecular-cell-biology

PIM1-dependent phosphorylation of Histone H3 at Serine 10 is required for MYC-dependent transcriptional activation and oncogenic transformation. 2007-06-19T14:34:45Z Salvatore Oliviero Alessio Zippo Alessandra De Robertis Riccardo Serafini Cancer Molecular Cell Biology The serine/threonine kinase PIM1, cooperates with MYC in cell cycle progression and tumorigenesis. However, the nature of this cooperation remains elusive. Here we show that PIM1 contributes to the transcriptional activation of MYC-target genes by phosphorylating the histone H3 nucleosome at Serine 10 (H3S10). Recombinant PIM1 directly phosphorylates H3S10 on the nucleosome _in vitro_. Following growth factor stimulation, PIM1 accumulates in the nucleus where it forms a complex with the MYC/MAX dimer via the MYC BoxII domain (MBII). Immunofluorescence analysis coupled with _in vivo_ run-on shows a high degree of PIM1 and MYC co-localization in the nucleus at sites of active transcription. Expression profile analysis revealed that PIM1 contributes to the regulation of 20% of the MYC-regulated genes. Chromatin immunoprecipitation (ChIP) analysis in MYC silenced cells demonstrates that MYC recruits PIM1 to the E boxes of the MYC-target genes FOSL1 (FRA1) and ID2. PIM1 knockdown as well as the over-expression of the kinase inactive mutant demonstrate that PIM1 is required for H3S10 phosphorylation at FOSL1 and ID2 MYC-binding sites and for their transcriptional activation. Moreover, we show that PIM1-dependent H3S10 phosphorylation contributes to MYC transforming capacity. These results establish a new function for PIM1 as a MYC cofactor that phosphorylates the chromatin at MYC-target loci and suggest that nucleosome phosphorylation, at E boxes, contributes to MYC-dependent transcriptional activation and cellular transformation. http://precedings.nature.com/documents/100/version/1 oai:nature.com:10101/npre.2007.100.1 http://hdl.handle.net/10101/npre.2007.100.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.104.1 2007-06-20T12:43:38Z cancer chemistry bioinformatics

The CombiUgi Project and Closing the Open Science Loop 2007-06-19T16:23:27Z Jean-Claude Bradley Rikesh Parikh Dan Zaharevitz Rajarshi Guha Cancer Chemistry Bioinformatics This presentation combines 2 blog posts explaining the CombiUgi project and the predicted anti-tumor activity of a virtual library of 68,000 compounds. http://precedings.nature.com/documents/104/version/1 oai:nature.com:10.1038/npre.2007.104.1 http://dx.doi.org/10.1038/npre.2007.104.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.129.1 2007-06-20T10:53:45Z molecular-cell-biology bioinformatics

Folding pathway of the B1 domain of protein G explored by a multiscale modeling 2007-06-20T13:55:34Z Andrzej Kolinski Sebastian Kmiecik Molecular Cell Biology Bioinformatics The understanding of the folding mechanisms of single domain proteins is an essential step in the understanding of protein folding in general. Recently, we developed a mesoscopic CABS protein model which was successfully applied in protein structure prediction, studies of protein thermodynamics and modeling of protein complexes. In the present research this model is employed in a detailed characterization of the folding process of a simple globular protein, the B1 domain of IgG-binding protein G (GB1). There is a vast body of experimental facts and theoretical findings for this protein. Performing unbiased, _ab initio_ simulations, we demonstrated that the GB1 folding proceeds via the successive formation of an extended folding nucleus, followed by slow structure fine-tuning. Remarkably, a subset of native interactions drives the folding from the very beginning. The emerging comprehensive picture of GB1 folding perfectly matches and extends the previous experimental and theoretical studies. http://precedings.nature.com/documents/129/version/1 oai:nature.com:10.1038/npre.2007.129.1 http://dx.doi.org/10.1038/npre.2007.129.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.130.1 2007-06-21T06:10:59Z biotechnology cancer

A potential role for Dkk-1 in the pathogenesis of osteosarcoma predicts novel diagnostic and treatment strategies. 2007-06-20T14:47:39Z Carl Gregory Narae Lee Angela Smolarz Scott Olson Odile David Jacob Reiser Robert Kutner Najat Daw Darwin Prockop Edwin Horwitz Biotechnology Cancer Canonical Wnt signaling is an osteo-inductive signal that promotes bone repair through acceleration of osteogenic differentiation by progenitors. Dkk-1 is a secreted inhibitor of canonical Wnt signaling and thus inhibits osteogenesis. To examine a potential osteo-inhibitory role of Dkk-1 in osteosarcoma (OS), we measured serum Dkk-1 in pediatric patients with OS (median age, 13.4 years) and found it to be significantly elevated. We also found that Dkk-1 was maximally expressed by the OS cells at the tumor periphery and _in vitro_ Dkk-1 and RANKL are co-expressed by rapidly proliferating OS cells. Both Dkk-1 and conditioned media from OS cells reduces osteogenesis by human mesenchymal cells and by immuno-depletion of Dkk-1, or by adding a GSK3[beta] inhibitor, the effects of Dkk-1 were attenuated. In mice, we found that the expression of Dkk-1 from implanted tumors was similar to the human tumor biopsies in that human Dkk-1 was present in the serum of recipient animals. These data demonstrate that systemic levels of Dkk-1 are elevated in osteosarcoma. Furthermore, the expression of Dkk-1 by the OS cells at the periphery of the tumor probably contributes to its expansion by inhibiting repair of the surrounding bone. These data demonstrate that Dkk-1 may serve as a prognostic or diagnostic marker for evaluation of OS and furthermore, immuno-depletion of Dkk-1 or administration of GSK3[beta] inhibitors could represent an adjunct therapy for this disease. http://precedings.nature.com/documents/130/version/1 oai:nature.com:10101/npre.2007.130.1 http://hdl.handle.net/10101/npre.2007.130.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.141.1 2007-06-20T17:32:39Z development molecular-cell-biology

Characterization of Fut10 and Fut11, Putative Alpha-1-3/4 Fucosyltransferase Genes Important for Vertebrate Development 2007-06-20T20:53:52Z Santosh K. Patnaik Developmental Biology Molecular Cell Biology Two new, putative alpha-1-3/4 fucosyltransferases ([alpha]1-3/4 Fuc-Ts), Fuc-TX and Fuc-TXI, were identified in the vertebrate genome and transcriptome sequence databases through sequence homology-based queries. These proteins have a significant sequence similarity to only [alpha]1-3/4 Fuc-Ts, and possess peptide motifs that are evolutionarily conserved among the known vertebrate [alpha]1-3/4 Fuc-Ts. However, Fuc-TX and Fuc-TXI lack the HH[R/W][D/E] sequence that determines the specificity for type 1 or 2 substrates among the known vertebrate enzymes, and Fuc-TXI proteins do not possess a transmembrane domain. The Fut10 and Fut11 genes that encode these proteins are expressed ubiquitously in the adult mouse and in the mouse embryo throughout development. Though a Fuc-T activity of the mouse proteins could not be detected, Fuc-TXI, but not Fuc-TX, was found to hydrolyze GDP-fucose. The interaction of Fuc-TXI with GDP-fucose was also confirmed by its binding to GDP-hexanolamine. In zebrafish, Fut11 transcripts could be detected during early embryonic development. A knock-down of Fuc-TXI in zebrafish embryos with Fut11-specific antisense morpholino oligonucleotides resulted in malformations of the posterior trunk and tail. http://precedings.nature.com/documents/141/version/1 oai:nature.com:10101/npre.2007.141.1 http://hdl.handle.net/10101/npre.2007.141.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.145.1 2007-06-21T04:58:15Z ecology plant-biology

Phyloclimatic Modelling: Phylogenies, Palaeo-climate and Environmental Preferences 2007-06-21T07:25:19Z Chris Yesson Alastair Culham Ecology Plant Biology A new technique is demonstrated for the interpretation of the role played by climate in plant diversity through the optimisation of climate variables on phylogenetic trees. This is achieved by calculating climate preferences for individual species based on established bioclimatic modelling techniques using point
distribution data from distributed sources. We demonstrate a new technique for optimising the component parameters on phylogenetic trees. These parameters can be re-combined into
bioclimatic models for ancestral nodes throughout the phylogenetic tree. The combination of DNA-sequence data and the fossil record is used to establish time-calibrated phylogenies. Using these chronograms, bioclimatic models can in turn can be projected into the relevant palaeo-climate scenario to establish possible areas of palaeo-distribution. This technique is demonstrated using exemplar plant groups from Mediterranean-type winter-wet climate zones. http://precedings.nature.com/documents/145/version/1 oai:nature.com:10.1038/npre.2007.145.1 http://dx.doi.org/10.1038/npre.2007.145.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.150.1 2007-06-21T07:04:20Z ecology plant-biology

Plants at risk from climate change 2007-06-21T09:07:47Z Chris Yesson Alastair Culham Ecology Plant Biology The popular garden flower Cyclamen grows natively in the Mediterranean. Climate change could make the region unsuitable for 18/21 species in 50 years time. Ant-dispersed Cyclamen can’t hope to migrate to suitable new areas without assistance.

Background: The impact of global climate change on plant distribution, speciation and extinction is of current concern. Examining species climatic preferences via bioclimatic niche modelling is a key tool to study this impact. There is an established link between bioclimatic niche models and phylogenetic diversification. A next step is to examine future distribution predictions from a phylogenetic perspective. We present such a study using Cyclamen (Myrsinaceae), a group which demonstrates morphological and phenological adaptations to its seasonal Mediterranean-type climate. How will the predicted climate change affect future distribution of this popular genus of garden plants? 
Results: We demonstrate phylogenetic structure for some climatic characteristics, and show that most Cyclamen have distinct climatic niches, with the exception of several wide-ranging, geographically expansive, species. We reconstruct climate preferences for hypothetical ancestral Cyclamen. The ancestral Cyclamen lineage has a preference for the seasonal Mediterranean climate characteristic of dry summers and wet winters. Future bioclimatic niches, based on BIOCLIM and Maxent models, are examined with reference to a future climate scenario for the 2050s. Over the next 50 years we predict a northward shift in the area of climatic suitability, with many areas of current distribution becoming climatically unsuitable. The area of climatic suitability for every Cyclamen species is predicted to decrease. For many species, there may be no areas with a suitable climate regardless of dispersal ability, these species re considered to be at high risk of extinction. This risk is examined from a phylogenetic
perspective.
Conclusion: Examining bioclimatic niches from a phylogenetic perspective permits novel interpretations of these models. In particular, reconstruction of ancestral niches can provide testable hypothesis about the historical development of lineages. In the future we can expect a northwards shift in climatic suitability for the genus Cyclamen. If this proves to be the case then dispersal is the best chance of survival, which seems highly unlikely for ant-dispersed Cyclamen. Human-assisted establishment of Cyclamen species well outside their native ranges offers hope and could provide the only means of dispersal to potentially suitable future environments. Even without human intervention the phylogenetic perspective demonstrates that major lineages could survive climate change even if many species are lost. http://precedings.nature.com/documents/150/version/1 oai:nature.com:10.1038/npre.2007.150.1 http://dx.doi.org/10.1038/npre.2007.150.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.153.1 2007-06-21T07:09:23Z bioinformatics

Revolutionizing scientific communication and collaboration 2007-06-21T10:15:59Z Konrad U. Foerstner Bioinformatics This presentation introduces new web-based ways of scientific communication and collaboration. It focuses on wikis and the _First Online EMBL PhD Symposium_ as an example of an online conference. http://precedings.nature.com/documents/153/version/1 oai:nature.com:10.1038/npre.2007.153.1 http://dx.doi.org/10.1038/npre.2007.153.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.164.1 2007-06-22T13:17:53Z immunology microbiology bioinformatics

Bacterial Capnine Blocks Transcription of Human Antimicrobial Peptides 2007-06-21T16:29:58Z Trevor G. Marshall Immunology Microbiology Bioinformatics The US CDC believes that 65% of all infections in developed countries may be caused by pathogens in biofilms. Electron Microscopy has shown that these bacterial communities can evade phagocytosis, and persist in the cytoplasm of monocytes, macrophages, lymphocytes and neutrophils. Three decades ago, Wirostko _et al._ found such intraphagocytic communities in Crohn’s disease, Juvenile Rheumatoid Arthritis and Sarcoidosis. However, the mechanism(s) by which such persistent bacteria could evade the immune system have remained elusive. Recently, 16S RNA from species of gliding bacteria never thought to be able to survive _in vivo_, have been found in surgically removed biofilms. This study set out to identify whether the genomes of these gliding bacteria might yield insight into mechanisms by which such persistent pathogens could evade phagocytosis. http://precedings.nature.com/documents/164/version/1 oai:nature.com:10.1038/npre.2007.164.1 http://dx.doi.org/10.1038/npre.2007.164.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.185.1 2007-06-22T14:11:06Z ecology plant-biology

A Meta-analysis of Studies on Plant Growth Rate and Allocation to Roots and Shoots 2007-06-22T17:33:12Z Daniel R. Taub Ecology Plant Biology I performed a meta-analysis of studies examining the relationships among nutrient availability, plant growth rate and allocation to roots vs. shoots. Species characteristic of high fertility habits grew faster than species characteristic of less fertile habitats. While species were highly plastic in root/shoot ratio, there was a strong correlation in root/shoot across fertility levels when plants were grown across fertility gradients. This suggests that the proportional mass allocation to roots is a consistent characteristic of individual species relative to other species. There was no consistent relationship between allocation to roots and either growth rate or the fertility of habitats that species typically are found in. http://precedings.nature.com/documents/185/version/1 oai:nature.com:10.1038/npre.2007.185.1 http://dx.doi.org/10.1038/npre.2007.185.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.196.1 2007-06-26T05:07:06Z neuroscience

Review: Dystroglycan in the Nervous System 2007-06-23T03:40:29Z Matthias Samwald Neuroscience Dystroglycan is part of a large complex of proteins, the dystrophin-glycoprotein complex, which has been implicated in the pathogenesis of muscular dystrophies for a long time. Besides muscular degeneration many patients manifest symptoms of neurological and cognitive dysfunction. Newer findings suggest that dystroglycan is implicated in brain development, synapse formation and plasticity, nerve-glia interactions and maintenance of the blood-brain barrier.
Most research so far has focused on the functions of dystroglycan in muscle and neuromuscular junctions, while its role in the brain and interneuronal synapses has been largely neglected. 
This review will give an overview of the biochemistry of dystroglycan, its interaction with other proteins as well as its confirmed and hypothetical functions in the nervous system in health and diesease. http://precedings.nature.com/documents/196/version/1 oai:nature.com:10.1038/npre.2007.196.1 http://dx.doi.org/10.1038/npre.2007.196.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.202.1 2007-06-25T04:51:48Z biotechnology bioinformatics

Simcluster: clustering enumeration gene expression data on the simplex space 2007-06-23T18:56:19Z Ricardo Z. N. Vêncio Leonardo A. B. Varuzza Carlos Pereira Helena Brentani Ilya Shmulevich Biotechnology Bioinformatics Transcript enumeration methods such as SAGE, MPSS, and sequencing-by-synthesis EST "digital northern", are important high-throughput techniques for digital gene expression measurement. As other counting or voting processes, these measurements constitute compositional data exhibiting properties particular to the simplex space where the summation of the components is constrained. These properties are not present on regular Euclidean spaces, on which hybridization-based microarray data is often modeled. Therefore, pattern recognition methods commonly used for microarray data analysis may be non-informative for the data generated by transcript enumeration techniques since they ignore certain fundamental properties of this space.

Here we present a software tool, Simcluster, designed to perform clustering analysis for data on the simplex space. We present Simcluster as a stand-alone command-line C package and as a user-friendly on-line tool. Both versions are available at: http://xerad.systemsbiology.net/simcluster.

Simcluster is designed in accordance with a well-established mathematical framework for compositional data analysis, which provides principled procedures for dealing with the simplex space, and is thus applicable in a number of contexts, including enumeration-based gene expression data. http://precedings.nature.com/documents/202/version/1 oai:nature.com:10.1038/npre.2007.202.1 http://dx.doi.org/10.1038/npre.2007.202.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.203.1 2007-06-25T05:21:52Z immunology bioinformatics evolutionary-biology

Evolution of malaria virulence in cross-generation transmission through selective immune pressure 2007-06-23T19:32:22Z David E. Gurarie Immunology Bioinformatics Evolutionary Biology Theoretical arguments and some mathematical models of host-parasite coevolution (e.g. [1- 6]) suggest host immunity as the driving source for the evolution of parasite virulence. Imperfect vaccines in particular, can play the role and recent work [7] sets to test these ideas experimentally, using the mouse malaria model, Plasmodium chabaudi. To this end the authors evolve parasite lines in immunized and nonimmunized (“naïve”) mice using serial passage of infected blood samples. They find parasite lines evolved in immunized mice become more virulent than those evolved in naive mice. Furthermore, this feature persisted even when the evolved strains were transmitted through mosquitoes. 
Here we develop a mathematical model of parasite dynamics that qualitatively reproduces the experimental results of [7]. Our model accounts for the basic in-host processes: (i) production and depletion of red blood cells (RBC); (ii) immune-modulated parasite growth/ replication, (iii) immune stimulation and clearing of parasite. Besides we introduce multiple parasite strains with variable levels of virulence, and allow random mutations during replication process. The virulence is represented by a single parameter – immune stimulation threshold. So more virulent strains have higher “tolerance levels”, hence increased RBC depletion (anemia). 
Numeric simulations with our model exhibit, as in [7] the overall evolution of virulence in serial passage of parasite strains, and its enhancement through partial (imperfect) immunization. http://precedings.nature.com/documents/203/version/1 oai:nature.com:10101/npre.2007.203.1 http://hdl.handle.net/10101/npre.2007.203.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.221.1 2007-06-25T11:37:08Z microbiology

Requirement of Activation for Hepatitis B Virus Infection 2007-06-25T15:01:44Z Michael Bruns Claudia Maenz Microbiology Although _in vitro_ models of human hepatitis B virus replication are established, so far none could approximate infection efficiency as expected from _in vivo_ observations. Susceptibility for HBV infections has only been reported for primary hepatocytes of human, chimpanzee or Tupaia belangeri and the cell line HepaRG. Here we show that the insusceptible human hepatoma cell line HepG2 can be infected, when the virus was beforehand activated by passage over whole duck liver cell cultures. That suggests an activation step to be performed by specialized liver cells. http://precedings.nature.com/documents/221/version/1 oai:nature.com:10101/npre.2007.221.1 http://hdl.handle.net/10101/npre.2007.221.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.235.1 2007-06-26T05:38:04Z chemistry pharmacology

The nitrite anion: the key intermediate in alkyl nitrates degradative mechanism. 2007-06-26T07:50:20Z Loris Grossi Chemistry Pharmacology Alkyl nitrates, _in vivo_, are metabolized to yield nitric oxide, and thiol groups are considered necessary cofactors. This statement is based on studies that underline how these species potentiate hemodynamic responsiveness to nitrates in patients with ischemic heart disease. However, the role of thiols might be mediated by the formation of corresponding S-nitrosothiols, and a redox process is responsible for the nitrates' degradation: an enzyme, probably the cytochrome P450, is involved _in vivo_. Here, we report evidence that, in vitro, no reaction between thiols and alkyl nitrates takes place, but that stronger reducing agents, such as iron (II) derivatives, are necessary: alkoxy radicals and the nitrite anion are the reaction intermediates. The latter, in slightly acidic conditions, for instance mimicking ischemic conditions, is shown to nitrosilate thiols to the corresponding S-nitrosothiols: the real NO suppliers. Therefore, the direct release of NO from nitrates is excluded. Finally, the in vivo role of thiols on depletion and tolerance is also accounted for. http://precedings.nature.com/documents/235/version/1 oai:nature.com:10101/npre.2007.235.1 http://hdl.handle.net/10101/npre.2007.235.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.241.1 2007-06-27T08:41:07Z ecology

Systema Naturae. Classification of living things. 2007-06-26T11:49:08Z Alexey Shipunov Ecology Original classification of living organisms containing four kingdoms (Monera, Protista, Vegetabilia and Animalia), 60 phyla and 253 classes, is presented. http://precedings.nature.com/documents/241/version/1 oai:nature.com:10.1038/npre.2007.241.1 http://dx.doi.org/10.1038/npre.2007.241.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.243.1 2007-06-26T10:35:10Z ecology bioinformatics plant-biology

Plant Transcription Factors @ uni-potsdam.de 2007-06-26T12:09:56Z Diego Mauricio Riaño-Pachón Ingo Dreyer Slobodan Ruzicic Bernd Mueller-Roeber Ecology Bioinformatics Plant Biology We present the Plant Transcription Factor Database (PlnTFDB), and the putative complete set of TFs in the algae _Chlamydomonas reinhardtii_, _Ostreococcus tauri_ and the vascular plants _Oryza sativa_ and _Arabidopsis thaliana_. http://precedings.nature.com/documents/243/version/1 oai:nature.com:10.1038/npre.2007.243.1 http://dx.doi.org/10.1038/npre.2007.243.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.262.1 2007-06-27T08:46:02Z neuroscience bioinformatics

Workshop report: 1st INCF Workshop on Large-scale Modeling of the Nervous System 2007-06-27T12:26:58Z Mikael Djurfeldt Anders Lansner Neuroscience Bioinformatics The goal of this workshop was to survey current demands, ongoing activities, and plans relating to development of tools for scalable neural network simulation. Areas covered included software components for preprocessing/model setup, as well
as for storage, analysis, and visualization of results. Participants discussed the need for coordinated action in the field with regard to model, method and tool development. The reports a description of the state-of-art in the field as well as recommendations for actions to facilitate infrastructure developments. http://precedings.nature.com/documents/262/version/1 oai:nature.com:10.1038/npre.2007.262.1 http://dx.doi.org/10.1038/npre.2007.262.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.278.1 2007-06-28T04:48:13Z bioinformatics

New checksum functions for Biopython 2007-06-28T02:42:15Z Sebastian Bassi Virginia Gonzalez Bioinformatics Checksum algorithms are used in biological databases for integrity check and identification purposes. CRC64 is the only checksum algorithm already included in Biopython. This work proposes two new implementation of known algorithms (GCG Checksum and SEGUID). There is also an application based on SEGUID: Looking for redundancy between two FASTA files full of protein sequences based only in sequence information, by comparing the SEGUIDs of both files.
The code is shown in the manuscript and may be available at Biopython.org. http://precedings.nature.com/documents/278/version/1 oai:nature.com:10.1038/npre.2007.278.1 http://dx.doi.org/10.1038/npre.2007.278.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.287.1 2007-06-28T10:26:08Z chemistry bioinformatics

XML in Motion from Genome to Drug 2007-06-28T13:33:26Z C. Gopi Mohan Chemistry Bioinformatics Information technology (IT) has emerged as a central to the solution of contemporary genomics and drug discovery problems. Researchers involved in genomics, proteomics, transcriptional profiling, high throughput structure determination, and in other sub-disciplines of bioinformatics have direct impact on this IT revolution. As the full genome sequences of many species, data from structural genomics, micro-arrays, and proteomics became available, integration of these data to a common platform require sophisticated bioinformatics tools. Organizing these data into knowledgeable databases and developing appropriate software tools for analyzing the same are going to be major challenges. XML (eXtensible Markup Language) forms the backbone of biological data representation and exchange over the internet, enabling researchers to aggregate data from various heterogeneous data resources. The present article covers a comprehensive idea of the integration of XML on particular type of biological databases mainly dealing with sequence-structure-function relationship and its application towards drug discovery. This e-medical science approach should be applied to other scientific domains and the latest trend in semantic web applications is also highlighted. http://precedings.nature.com/documents/287/version/1 oai:nature.com:10.1038/npre.2007.287.1 http://dx.doi.org/10.1038/npre.2007.287.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.290.1 2007-06-28T13:30:55Z earth-and-environment

Changes in temperature-moisture covariance could increase soil carbon loss 2007-06-28T15:57:57Z Asko S. Noormets Michael Gavazzi Sara Strickland Ge Sun Jiquan Chen John King Steve G. McNulty Earth & Environment Soils store about 1.5x10^16 g of carbon (C), about as much as terrestrial vegetation and atmosphere combined 1. The complex interplay between factors that regulate C release from soil through respiration is not completely understood, but could potentially exert strong influence on global radiation balance and climate change2. Respiration exerts strong effect on the spatial heterogeneity of terrestrial C cycle 3 and its temporal variation remains more poorly understood compared to gross ecosystem production (GEP) 4. This variation can analytically be attributed to changes in environmental factors, but forecasting individual deviations remains a challenge 4. Here we propose that deviations of the typical covariance pattern of primary environmental drivers (temperature, T, and moisture, presented in this study as volumetric water content, VWC) may affect the deviations of respiratory C loss. Typically, T and VWC are inversely related, with warm periods being generally drier and vice versa, and therefore the stimulating effect of one factor is counterbalanced by unfavorable levels of the other 5. However, should the driving variables be positively related, respiratory carbon release can increase significantly (Supplementary Fig. 1a). This hypothesis is supported by two consecutive years of ecosystem-level and soil carbon exchange data that differed in rain fall periodicity and T-VWC-covariance. With changing climate patterns, including the intensity and frequency of rainfall events, there is the possibility that the covariance patterns of T and VWC may change, and more frequent periods of positive T-VWC covariance may lead to greater loss of soil carbon, and contribute to greater radiative forcing on Earth’s energy budget. http://precedings.nature.com/documents/290/version/1 oai:nature.com:10101/npre.2007.290.1 http://hdl.handle.net/10101/npre.2007.290.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.306.1 2007-07-02T09:20:53Z biotechnology bioinformatics

The Reproducibility of Lists of Differentially Expressed Genes in Microarray Studies 2007-06-29T19:45:48Z Leming Shi Wendell D. Jones Roderick V. Jensen Stephen C. Harris Roger G. Perkins Federico M. Goodsaid Lei Guo Lisa J. Croner Cecilie Boysen Hong Fang Shashi Amur Wenjun Bao Catalin C. Barbacioru Vincent Bertholet Xiaoxi Megan Cao Tzu-Ming Chu Patrick J. Collins Xiao-hui Fan Felix W. Frueh James C. Fuscoe Xu Guo Jing Han Damir Herman Huixiao Hong Ernest S. Kawasaki Quan-Zhen Li Yuling Luo Yunqing Ma Nan Mei Ron L. Peterson Raj K. Puri Feng Qian Richard Shippy Zhenqiang Su Yongming Andrew Sun Hongmei Sun Brett Thorn Yaron Turpaz Charles Wang Sue-Jane Wang Janet A. Warrington James C. Willey Jie Wu Qian Xie Liang Zhang Lu Zhang Sheng Zhong James J. Chen Russell D. Wolfinger Weida Tong Biotechnology Bioinformatics Reproducibility is a fundamental requirement in scientific experiments and clinical contexts. Recent publications raise concerns about the reliability of microarray technology because of the apparent lack of agreement between lists of differentially expressed genes (DEGs). In this study we demonstrate that (1) such discordance may stem from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion, the lists become much more reproducible, especially when fewer genes are selected; and (3) the instability of short DEG lists based on P cutoffs is an expected mathematical consequence of the high variability of the t-values. We recommend the use of FC ranking plus a non-stringent P cutoff as a baseline practice in order to generate more reproducible DEG lists. The FC criterion enhances reproducibility while the P criterion balances sensitivity and specificity. http://precedings.nature.com/documents/306/version/1 oai:nature.com:10.1038/npre.2007.306.1 http://dx.doi.org/10.1038/npre.2007.306.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.320.1 2007-07-02T10:14:53Z ecology plant-biology evolutionary-biology

Third-codon transversion rate-based _Nymphaea_ basal angiosperm phylogeny -- concordance with developmental evidence 2007-07-02T13:10:17Z Xiaohan Yang Gerald A. Tuskan Timothy J. Tschaplinski (Max) Zong-Ming Cheng Ecology Plant Biology Evolutionary Biology Flowering plants (angiosperms) appeared on Earth rather suddenly approximately 130 million years ago and underwent a massive expansion in the subsequent 10-12 million years. Current molecular phylogenies have predominantly identified _Amborella_, followed by _Nymphaea_ (water lilies) or _Amborella_ plus _Nymphaea_, in the ANITA clade (_Amborella_, Nymphaeales, Illiciaceae, Trimeniaceae and Austrobaileyaceae) as the earliest angiosperm. However, developmental studies suggest that the earliest angiosperm had a 4-cell/4-nucleus female gametophyte and a diploid endosperm represented by _Nymphaea_, suggesting that _Amborella_, having an 8-cell/9-nucleus female gametophyte and a triploid endosperm, cannot be representative of the basal angiosperm. This evolution-development discordance is possibly caused by erroneous inference based on phylogenetic signals with low neutrality and/or high saturation. Here we show that the 3rd codon transversion (P3Tv), with high neutrality and low saturation, is a robust high-resolution phylogenetic signal for such divergences and that the P3Tv-based land plant phylogeny cautiously identifies _Nymphaea_, followed by _Amborella_, as the most basal among the angiosperm species examined in this study. This P3Tv-based phylogeny contributes insights to the origin of angiosperms with concordance to fossil and stomata development evidence. http://precedings.nature.com/documents/320/version/1 oai:nature.com:10.1038/npre.2007.320.1 http://dx.doi.org/10.1038/npre.2007.320.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.306.2 2007-07-03T12:18:21Z biotechnology bioinformatics

The Reproducibility of Lists of Differentially Expressed Genes in Microarray Studies 2007-07-02T15:49:20Z Leming D. Shi Wendell D. Jones Roderick V. Jensen Stephen C. Harris Roger G. Perkins Federico M. Goodsaid Lei Guo Lisa J. Croner Cecilie Boysen Hong Fang Shashi Amur Wenjun Bao Catalin C. Barbacioru Vincent Bertholet Xiaoxi Megan Cao Tzu-Ming Chu Patrick J. Collins Xiao-hui Fan Felix W. Frueh James C. Fuscoe Xu Guo Jing Han Damir Herman Huixiao Hong Ernest S. Kawasaki Quan-Zhen Li Yuling Luo Yunqing Ma Nan Mei Ron L. Peterson Raj K. Puri Feng Qian Richard Shippy Zhenqiang Su Yongming Andrew Sun Hongmei Sun Brett Thorn Yaron Turpaz Charles Wang Sue-Jane Wang Janet A. Warrington James C. Willey Jie Wu Qian Xie Liang Zhang Lu Zhang Sheng Zhong Russell D. Wolfinger Weida Tong Biotechnology Bioinformatics Reproducibility is a fundamental requirement in scientific experiments and clinical contexts. Recent publications raise concerns about the reliability of microarray technology because of the apparent lack of agreement between lists of differentially expressed genes (DEGs). In this study we demonstrate that (1) such discordance may stem from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion, the lists become much more reproducible, especially when fewer genes are selected; and (3) the instability of short DEG lists based on P cutoffs is an expected mathematical consequence of the high variability of the t-values. We recommend the use of FC ranking plus a non-stringent P cutoff as a baseline practice in order to generate more reproducible DEG lists. The FC criterion enhances reproducibility while the P criterion balances sensitivity and specificity. http://precedings.nature.com/documents/306/version/2 oai:nature.com:10101/npre.2007.306.2 http://hdl.handle.net/10101/npre.2007.306.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.326.1 2007-07-09T22:13:51Z biotechnology

Exploiting Nonlinear Recurrence and Fractal Scaling Properties for Voice Disorder Detection 2007-07-02T21:52:21Z Max A. Little Patrick E. McSharry Stephen A. Roberts Declan A. E. Costello Irene M. Moroz Biotechnology Background: Voice disorders affect patients profoundly, and acoustic tools can potentially measure voice function objectively. Disordered sustained vowels exhibit wide-ranging phenomena, from nearly periodic to highly complex, aperiodic vibrations, and increased "breathiness". Modelling and surrogate data studies have shown significant nonlinear and non-Gaussian random properties in these sounds. Nonetheless, existing tools are limited to analysing voices displaying near periodicity, and do not account for this inherent biophysical nonlinearity and non-Gaussian randomness, often using linear signal processing methods insensitive to these properties. They do not directly measure the two main biophysical symptoms of disorder: complex nonlinear aperiodicity, and turbulent, aeroacoustic, non-Gaussian randomness. Often these tools cannot be applied to more severe disordered voices, limiting their clinical usefulness.

Methods: This paper introduces two new tools to speech analysis: recurrence and fractal scaling, which overcome the range limitations of existing tools by addressing directly these two symptoms of disorder, together reproducing a "hoarseness" diagram. A simple bootstrapped classifier then uses these two features to distinguish normal from disordered voices.

Results: On a large database of subjects with a wide variety of voice disorders, these new techniques can distinguish normal from disordered cases, using quadratic discriminant analysis, to overall correct classification performance of 91.8% plus or minus 2.0%. The true positive classification performance is 95.4% plus or minus 3.2%, and the true negative performance is 91.5% plus or minus 2.3% (95% confidence). This is shown to outperform all combinations of the most popular classical tools.

Conclusions: Given the very large number of arbitrary parameters and computational complexity of existing techniques, these new techniques are far simpler and yet achieve clinically useful classification performance using only a basic classification technique. They do so by exploiting the inherent nonlinearity and turbulent randomness in disordered voice signals. They are widely applicable to the whole range of disordered voice phenomena by design. These new measures could therefore be used for a variety of practical clinical purposes.
 http://precedings.nature.com/documents/326/version/1 oai:nature.com:10101/npre.2007.326.1 http://hdl.handle.net/10101/npre.2007.326.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.329.1 2007-07-03T04:44:39Z ecology

Natural Diet of an Australian Freshwater Pipefish 2007-07-03T00:08:52Z Andrew W. Jones Lars G. Rudstam Thomas S. Rayner Ecology Globally, the family Syngnathidae (seahorses and pipefish) is recognized as being both under threat from anthropogenic pressures and poorly studied. Of the 47 species that are listed on the IUCN Red List, 33 are currently listed as ‘data deficient’, with inadequate information available to make an assessment of their risk of extinction. Within Australia, this has prompted environmental assessments of specific fisheries, as well as a number of recent ecological studies of marine syngnathids. However, no work has been published on the continent’s four freshwater species. To begin to remedy this, a thorough analysis of the feeding habits of one such species was conducted. Twenty-two specimens of _Hippichthys heptagonus_ Bleeker, 1849 were collected from the Mulgrave River in north Queensland. Dissection and subsequent analysis revealed that microcrustaceans comprised the vast majority of the species diet, with calanoid and cyclopoid copepods being by far the most prevalent prey items (66%). Dipteran, as well as ephemeropteran, larvae were moderately abundant (5% and 10%), and made a notable contribution to the volume of the average diet (16% and 12%). A percent principal component analysis of the volume data reinforced these findings. The first factor accounted for 69.7% of the observed variation, with largest factor loading (0.88) belonging to copepods. there were no significant differences in prey consumption Between genders, but, the percent volume of copepod prey significantly higher in adults was than in juveniles (Mann-Whitney’s U: P < 0.01). These findings indicate that _H. heptagonus_ is primarily a predaceous planktivore, with a specialized diet that is comparable to coastal marine syngnathids. Also, the prevalence of a single prey type suggests that the _H. heptagonus_ occupies a narrow ecological niche, and that its distribution within the watershed may be limited by prey availability. http://precedings.nature.com/documents/329/version/1 oai:nature.com:10.1038/npre.2007.329.1 http://dx.doi.org/10.1038/npre.2007.329.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.331.1 2007-07-03T08:55:24Z bioinformatics

Data integration in myGrid with Taverna 2007-07-03T09:30:59Z Duncan Hull Bioinformatics Many areas of life sciences research involve integrating terabytes of heterogeneous, 
distributed and autonomous data available on the Web. The myGrid project has addressed 
these challenging problems by developing and applying novel grid and semantic web 
services technology to life science data integration, particularly genome annotation and 
microarray analysis. This presentation outlines the past, present and future of the Taverna workflow system.
 http://precedings.nature.com/documents/331/version/1 oai:nature.com:10.1038/npre.2007.331.1 http://dx.doi.org/10.1038/npre.2007.331.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.353.1 2007-07-05T04:44:15Z immunology bioinformatics

Review of Immunoinformatic approaches to in-silico B-cell epitope prediction 2007-07-05T03:01:41Z Rick Reitmaier Immunology Bioinformatics In this paper, the current state of in-silico, B-cell epitope prediction is discussed. Recommendations for improving some of the approaches encountered are outlined, along with the presentation of an entirely novel technique, which uses molecular mechanics for epitope classification, evaluation and prediction. http://precedings.nature.com/documents/353/version/1 oai:nature.com:10.1038/npre.2007.353.1 http://dx.doi.org/10.1038/npre.2007.353.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.354.1 2007-07-05T05:06:02Z neuroscience

Angiotensinergic innervation of rat and human mesenteric resistant blood vessels 2007-07-05T07:58:49Z Jaspal Patil Eva Heiniger Thomas Schaffner Oliver Muhlemann Hans Imboden Neuroscience In contrast to the current believe that angiotensin II (Ang II) only interacts with the sympathetic nervous system (SNS) as a circulating hormone, we document here the existence of an endogenous renin-angiotensin system (RAS) in the sympathetic coeliac ganglion and the angiotensinergic innervation with mesenteric resistant blood vessels. Our findings indicate that Ang II is synthesized inside the neurons of sympathetic coeliac ganglion and may act as an endogenous neurotransmitter locally on the mesenteric resistant blood vessels. http://precedings.nature.com/documents/354/version/1 oai:nature.com:10101/npre.2007.354.1 http://hdl.handle.net/10101/npre.2007.354.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.359.1 2007-07-05T11:57:47Z genetics bioinformatics

Estimation of the Multiple Testing Burden for Genomewide Association Studies of Common Variants 2007-07-05T14:54:46Z Itsik Pe'er Roman Yelensky David Altshuler Mark J. Daly Genetics & Genomics Bioinformatics Genomewide association studies are an exciting strategy in genetics, recently becoming feasible. While pioneering studies are being underway, it is already clear that the analytic issue of determining the significance of results presents a challenge to the wide community of researchers. Rather than each study engaging in independent evaluation, there is need in the community to have standards set for whole-genome significance. 
We have therefore undertaken the task of developing such standards, based on data collected with collaborators in the International Haplotype Map Consortium. We report an estimated burden of a million independent tests genomewide in Europeans, and twice that number in Africans. We further identify the sensitivity of the testing burden to the required significance level, with implications to staged design of association studies.
 http://precedings.nature.com/documents/359/version/1 oai:nature.com:10101/npre.2007.359.1 http://hdl.handle.net/10101/npre.2007.359.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.361.1 2007-07-05T13:07:43Z bioinformatics

Sharing Detailed Research Data Is Associated with Increased Citation Rate 2007-07-05T15:24:45Z Heather A. Piwowar Bioinformatics Presentation based on the publication here:
Piwowar HA, Day RS, Fridsma DB (2007) Sharing Detailed Research Data Is Associated with Increased Citation Rate. PLoS ONE 2(3): e308. doi:10.1371/journal.pone.0000308

Sharing research data provides benefit to the general scientific community, but the benefit is less obvious for the investigator who makes his or her data available.

We examined the citation history of 85 cancer microarray clinical trial publications with respect to the availability of their data. The 48% of trials with publicly available microarray data received 85% of the aggregate citations. Publicly available data was significantly (p = 0.006) associated with a 69% increase in citations, independently of journal impact factor, date of publication, and author country of origin using linear regression.

This correlation between publicly available data and increased literature impact may further motivate investigators to share their detailed research data.

 http://precedings.nature.com/documents/361/version/1 oai:nature.com:10.1038/npre.2007.361.1 http://dx.doi.org/10.1038/npre.2007.361.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.369.1 2007-07-06T04:42:39Z biotechnology genetics bioinformatics

ProbCD: enrichment analysis accounting for categorization uncertainty 2007-07-06T04:45:05Z Ricardo Vêncio Ilya Shmulevich Biotechnology Genetics & Genomics Bioinformatics As in many other areas of science, systems biology makes extensive use of statistical association and significance estimates in contingency tables, a type of categorical data analysis known in this field as enrichment (also over-representation or enhancement) analysis. In spite of efforts to create probabilistic annotations, especially in the Gene Ontology context, or to deal with uncertainty in high throughput-based datasets, current enrichment methods largely ignore this probabilistic information since they are mainly based on variants of the Fisher Exact Test. We developed an open-source R package to deal with probabilistic categorical data analysis, ProbCD, that does not require a static contingency table. The contingency table for
the enrichment problem is built using the expectation of a Bernoulli Scheme stochastic process given the categorization probabilities. An on-line interface was created to allow usage by non-programmers and is available at: http://xerad.systemsbiology.net/ProbCD/. We present an analysis framework and software tools to address the issue of uncertainty in categorical data analysis. In particular, concerning the enrichment analysis, ProbCD can accommodate: (i) the stochastic nature of the high-throughput experimental techniques and (ii) probabilistic gene annotation. http://precedings.nature.com/documents/369/version/1 oai:nature.com:10101/npre.2007.369.1 http://hdl.handle.net/10101/npre.2007.369.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.371.1 2007-07-08T07:55:18Z neuroscience

The Freezing Rotation Illusion 2007-07-06T07:31:23Z Max R. Dürsteler Neuroscience The freezing rotation illusion arises when a figure is continuously rotating in front of a back and forth rotating ground. The term “freezing rotation” designates the decrease in the perceived rotation speed of a figure when the figure and the ground are turning in equal directions. Subjects had to estimate the rotation speed of a continuously turning figure while the ground was either turning opposite to or with the figure. Their estimations of the figure’s speed were significantly lower, when the ground was moving in the same direction as the figure. In control experiments subjects had to estimate the ground’s speed while the figure was turning opposite to or with the ground. Overall, their estimations of the rotational speed of the ground were not significantly influenced by the rotational direction of the figure. http://precedings.nature.com/documents/371/version/1 oai:nature.com:10101/npre.2007.371.1 http://hdl.handle.net/10101/npre.2007.371.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.378.1 2007-07-06T15:56:10Z bioinformatics

Epigrass: a tool to study disease spread in complex networks. 2007-07-06T16:25:55Z Flávio Codeço Coelho Claudia Codeco Oswaldo Cruz Bioinformatics The construction of complex statial simulation models such as those used in network epidemiology, is a daunting task due to the large amount of data involved in their parameterization. Such data, which frequently resides on large geo-referenced databases, has to be processed and assigned to the various components of the model. All this just to construct the model, then it still has to be simulated and analyzed under different epidemiological scenarios. This workflow can only be achieved efficiently by computational tools that can automate most if not all these time-consuming tasks. In this paper, we present a simulation software, Epigrass, aimed to help designing and simulating network-epidemic models with any kind of node behavior.
 
A Network epidemiological model representing the spread of a directly transmitted disease through a bus-transportation network connecting mid-size cities in Brazil. Results show that the topological context of the starting point of the epidemic is of great importance from both control and preventive perspectives.

Epigrass is shown to facilitate greatly the construction, simulation and analysis of complex network models. The output of model results in standard GIS file formats facilitate the post-processing and analysis of results by means of sophisticated GIS software. http://precedings.nature.com/documents/378/version/1 oai:nature.com:10101/npre.2007.378.1 http://hdl.handle.net/10101/npre.2007.378.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.385.1 2007-07-10T13:59:11Z ecology genetics

Swine Influenza A Evolution via Recombination - Genetic Drift Reservoir 2007-07-07T03:02:44Z Henry L. Niman Ecology Genetics & Genomics The looming influenza pandemic has focused attention^1-4^ on the rapid evolution of H5N1 and other human and avian serotypes. The basic tenets of influenza genetics^5^ define gradual changes as drifts caused by point mutations created by a polymerase that lacks a proof reading function. More abrupt changes have been linked to reassortment, which shuffles the eight sub-genomic segments of the influenza genome in dually infected host. The complex evolution of these viruses has created a challenge in vaccine development. Swine influenza isolates from 2003 and 2004 have been identified^6^ that have acquired a human influenza gene, PB1. My analysis of the eight gene segments found large portions of two genes, PB2 and PA, which were identical matches with 1977 swine isolates^7,8^. Additional regions were exact matches with 1998 and 2002 isolates,^9,10^ demonstrating homologous recombination between earlier genomes. The absolute fidelity discounts the role of point mutations in gene drift. Moreover the human PB1 gene represented a reservoir for acquisition of polymorphisms in human seasonal flu. These observations challenge the basic tenets of influenza genetics and provide a method for predicting the changes in seasonal and pandemic influenza, as well as other rapidly evolving genomes. http://precedings.nature.com/documents/385/version/1 oai:nature.com:10101/npre.2007.385.1 http://hdl.handle.net/10101/npre.2007.385.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.391.1 2007-07-09T05:25:14Z biotechnology molecular-cell-biology

Quantification of Cell Movement Reveals Distinct Edge Motility Types During Cell Spreading 2007-07-08T07:36:26Z Benjamin J. Dubin-Thaler Jake M. Hofman Harry V. Xenias Ingrid A. Spielman Anna H. Shneidman Lawrence David Hans-Guenther Dobereiner Chris Wiggins Michael P. Sheetz Biotechnology Molecular Cell Biology Actin-based motility is central to cellular processes such as migration, bacterial engulfment, and cancer metastasis, and requires precise spatial and temporal regulation of the cytoskeleton. We studied one such process, fibroblast spreading, which involves three temporal phases: early, middle, and late spreading, distinguished by differences in cell area growth. In these studies, aided by improved algorithms for analyzing edge movement, we observed that each phase was dominated by a single, kinematically and biochemically distinct cytoskeletal organization, or motility type. Specifically, early spreading was dominated by periodic blebbing; continuous protrusion occurred predominantly during middle spreading; and periodic contractions were prevalent in late spreading. Further characterization revealed that each motility type exhibited a distinct distribution of the actin-related protein VASP, while inhibition of actin polymerization by cytochalasin D treatment revealed different dependences on barbed-end polymerization. Through this detailed characterization and graded perturbation of the system, we observed that although each temporal phase of spreading was dominated by a single motility type, in general cells exhibited a variety of motility types in neighboring spatial domains of the plasma membrane edge. These observations support a model in which global signals bias local cytoskeletal biochemistry in favor of a particular motility type. http://precedings.nature.com/documents/391/version/1 oai:nature.com:10101/npre.2007.391.1 http://hdl.handle.net/10101/npre.2007.391.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.400.1 2007-07-10T05:01:19Z genetics immunology

Effective Sample Size: Quick Estimation of the Effect of Related Samples in Genetic Case-Control Association Analyses 2007-07-09T21:41:11Z Yaning B. Yang Elaine L. Remmers Chukwuma Ogunwole Daniel Kastner Peter K. Gregersen Wentian F. Li Genetics & Genomics Immunology Correlated samples have been frequently avoided in case-control
genetic association
 studies in part because the methods for handling them are either not
easily implemented or not widely known. We
advocate one method for case-control association analysis of correlated
samples -- the effective sample size method -- as a simple and
accessible approach that does not require specialized computer programs.
The effective sample size method captures the variance inflation
of allele frequency estimation exactly, and can be used to modify the
chi-square test statistic, p-value, and 95% confidence interval of
odds-ratio simply by replacing the apparent number of allele counts with the
effective ones. For genotype frequency estimation, although a single
effective sample size is unable to completely characterize the variance inflation,
an averaged one can satisfactorily approximate the simulated result.
The effective sample size method is applied to the rheumatoid arthritis
siblings data collected from the North American Rheumatoid Arthritis Consortium (NARAC)
to establish a significant association with the interferon-induced
helicasel gene (IFIH1) previously being identified as a type 1 diabetes
susceptibility locus. Connections between the effective sample size
method and other methods, such as generalized estimation equation,
variance of eigenvalues for correlation matrices, and genomic controls,
are also discussed.
 http://precedings.nature.com/documents/400/version/1 oai:nature.com:10101/npre.2007.400.1 http://hdl.handle.net/10101/npre.2007.400.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.413.1 2007-07-12T10:03:03Z ecology molecular-cell-biology neuroscience

Looking at the Beginnings: Enquiries about Emergence of Cognition in Evolution 2007-07-10T20:07:14Z Walter Riofrio Ecology Molecular Cell Biology Neuroscience Trying to understand when and how the cognitive phenomena arise in evolution continues being a hard problem of confronting. 
One important task is to find the ways in which we will be able to arrive at those explanations that will enable us to understand how living beings put together perceived sensory information as well as how they represent it. 
In this presentation, we address some conceptual questions involved in the relationships between sensorial information perceived by brains and its representational capacities. 
 http://precedings.nature.com/documents/413/version/1 oai:nature.com:10.1038/npre.2007.413.1 http://dx.doi.org/10.1038/npre.2007.413.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.425.1 2007-07-17T13:13:40Z bioinformatics

Examining the uses of shared data 2007-07-11T15:47:47Z Heather A. Piwowar Douglas B. Fridsma Bioinformatics Background
 Many initiatives and repositories exist to encourage the sharing of research data, and thousands of microarray gene expression datasets are publicly available. Many studies reuse this data, but it is not well understood which datasets are reused and for what purpose.

 Materials and Methods
 We trained a machine-learning algorithm to automatically classify full-text gene expression microarray studies into two classes: those that generated original microarray data (n=900) and those which only reused data (n=250). We then compared the Medical Subject Heading (MeSH) terms of two classes to identify MeSH topics which were over- or under-represented by publications with reused data.

 Results
 Studies on humans, mice, chordata, and invertebrates were equally likely to be conducted using original or shared microarray data, whereas shared data was used in a relatively high proportion of studies involving fungi (odds ratio (OR)=2.4), and a relatively low proportion involving rats, bacteria, viruses, plants, or genetically-altered or inbred animals (OR<0.05). Unsurprisingly, when we looked at Major MeSH terms to represent the primary purpose of the studies, statistical and computational methods clearly dominated. The only biomedical topics with a relatively high proportion of data reuse Major MeSH terms were Promoter Regions, Evolution, and Protein Interaction Mapping.

 Discussion
 Identifying areas of particularly successful microarray data reuse—such as Saccharomyces cerevisiae datasets and studies of promoter regions and evolution—can highlight best practices to be used when developing research agendas, tools, standards, repositories, and communities in areas which have yet to receive major benefits from shared data.
 http://precedings.nature.com/documents/425/version/1 oai:nature.com:10.1038/npre.2007.425.1 http://dx.doi.org/10.1038/npre.2007.425.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.428.1 2007-08-13T05:14:01Z chemistry genetics evolutionary-biology

Application of a periodic table for the genetic code to influenza A/H3N2 virus 2007-07-11T23:44:40Z Susumu Morimoto Chemistry Genetics & Genomics Evolutionary Biology If biologists can utilize a table to have access to biological phenomena in the manner analogous to the periodic table for chemical elements, they may get hold of a directing post in life science. Currently the mutational rule of influenza viruses have remained perplexed and to reveal it should be now desired when avian influenza virus has just then threatened human beings. Here I examine the applicability of a novel periodic table for the genetic code to influenza A/H3N2 virus, while presenting two rules regarding single point mutations of its virus hemagglutinin gene. One rule is that non-synonymous single point mutations are intimately associated with the first or second base replacements between four groups (5, 6, 9, and 10) in the periodic table. Another rule is that there is a new index (inversion number) conserving in mutation. This paper will take the first step to such contribution of mutational reactions. http://precedings.nature.com/documents/428/version/1 oai:nature.com:10101/npre.2007.428.1 http://hdl.handle.net/10101/npre.2007.428.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.433.1 2007-07-12T06:10:54Z neuroscience bioinformatics

Reducing the Probability of False Positive Research Findings by Pre-Publication Validation - Experience with a Large Multiple Sclerosis Database 2007-07-12T06:25:09Z Martin M. Daumer Ulrike U. Held Katja K. Ickstadt Moritz M. Heinz Siegfried S. Schach George G. Ebers Neuroscience Bioinformatics *Objective*
We have assessed the utility of a pre-publication validation policy in reducing the probability of publishing false positive research findings. 
*Study design and setting*
The large database of the Sylvia Lawry Centre for Multiple Sclerosis Research was split in two parts: one for hypothesis generation and a validation part for confirmation of selected results. We present case studies from 5 finalized projects that have used the validation policy and results from a simulation study.
*Results*
In one project, the "relapse and disability" project as described in section II (example 3), findings could not be confirmed in the validation part of the database. The simulation study showed that the percentage of false positive findings can exceed 20% depending on variable selection. 
*Conclusion*
We conclude that the validation policy has prevented the publication of at least one research finding that could not be validated in an independent data set (and probably would have been a "true" false-positive finding) over the past three years, and has led to improved data analysis, statistical programming, and selection of hypotheses. The advantages outweigh the lost statistical power inherent in the process. http://precedings.nature.com/documents/433/version/1 oai:nature.com:10101/npre.2007.433.1 http://hdl.handle.net/10101/npre.2007.433.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.435.1 2007-07-13T05:42:14Z genetics

A periodic pattern of SNPs in the human genome 2007-07-12T07:49:43Z Bo Eskerod Madsen Palle Villesen Carsten Wiuf Genetics & Genomics By surveying all validated SNPs in the human genome we have found that SNPs positioned 1, 2, 4, 6 or 8 bp apart are more frequent than SNPs 3, 5, 7 or 9 bp apart. This holds even when we correct for nucleotide frequencies and site dependencies in nucleotide usage in the genome. The observed pattern is not restricted to any of the genomic regions that might give sequencing or alignment errors; i.e. transposable elements (SINE, LINE and LTR), tandem repeats and large duplicated regions. However we can define periodic DNA, which virtually capture the entire pattern. Periodic DNA is defined as small DNA sequences (16.9 bp average length) with a high degree of periodicity in nucleotide usage. Periodic DNA is widely distributed in the genome, underrepresented in exons, widespread in transcripts and slightly overrepresented in tandem repeats. Furthermore periodic DNA has a 1.8 times higher SNP density than the rest of the genome.
A possible biological explanation of these observations is that during DNA replication small fragments of (periodic) DNA is copied to nearby positions, substituting the original sequence. If the copied fragment differs from the original sequence a new SNP is created. 
In conclusion these observations suggest that not all SNPs in the human genome are created by independent single nucleotide mutations.
 http://precedings.nature.com/documents/435/version/1 oai:nature.com:10.1038/npre.2007.435.1 http://dx.doi.org/10.1038/npre.2007.435.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.437.1 2007-07-13T11:57:13Z pharmacology

Allosteric modulation of beta1 integrin function induces lung repair in animal model of emphysema. 2007-07-12T10:54:01Z Rehab J. Al-Jamal Linda Wilson Chris J. Armit Susan McIntyre Mark Marsden Steven D. Shapiro David J. Harrison Pharmacology Emphysema is a progressive lung disease characterised by loss of lung parenchyma with associated functional changes including decreased tissue elastance. Here we report beta1 integrin is a novel target for tissue repair and regeneration in emphysema. We show a single dose of a monoclonal antibody against beta1 integrin induced both functional and structural reversal of elastase-induced lung injury in vivo, and we found that similar matrix remodelling changes occurred in human lung tissue. We also identified a potential mechanism of action as this allosteric modulation of beta1 integrin inhibited elastase-induced caspase activation, F-actin aggregate formation and changes in cellular ATP levels. This was accompanied by maintenance of beta1?integrin levels and inhibition of caveolin-1 phosphorylation. We propose that allosteric modulation of beta1 integrin-mediated mechanosensing prevents cell death associated with lung injury and progressive emphysema, thus allowing cells to survive and for repair and regeneration to ensue. http://precedings.nature.com/documents/437/version/1 oai:nature.com:10101/npre.2007.437.1 http://hdl.handle.net/10101/npre.2007.437.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.444.1 2007-07-12T14:33:53Z biotechnology cancer chemistry molecular-cell-biology

Direct fluorophore conjugation to genomic DNA for microarray-based epigenomic profiling 2007-07-12T16:09:38Z Vineet Gupta Biotechnology Cancer Chemistry Molecular Cell Biology A methodology for microarray based epigenomic profiling is presented. The method relies on platinum-based fluorescence labeling reagents for direct (non-enzymatic) labeling of DNA and RNA. This is a work in progress and only preliminary data is presented here. http://precedings.nature.com/documents/444/version/1 oai:nature.com:10.1038/npre.2007.444.1 http://dx.doi.org/10.1038/npre.2007.444.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.446.1 2007-07-12T17:09:03Z earth-and-environment

Multi-site precipitation downscaling via an expanded conditional density network 2007-07-12T18:56:16Z Alex J. Cannon Earth & Environment Statistical downscaling models are used to estimate weather data at a station or stations based on atmospheric circulation data defined at a coarser resolution, for example gridded outputs from a Global Climate Model (GCM). Downscaled data can be used as inputs to environmental models that require finer-scale climate fields than are currently available from GCMs. Maintaining realistic downscaling relationships between sites and variables is particularly important in hydrological models, as streamflow depends strongly on the spatial distribution of precipitation in a watershed and on interactions with temperature that determine whether precipitation falls as rain or snow. More generally, precipitation is a difficult variable to downscale because of its non-normal distribution and its spatial and temporal patchiness.

A downscaling algorithm for daily precipitation series at multiple stations is presented. The expanded conditional density network (ECDN) models the conditional density of the Poisson-gamma distribution via an artificial neural network. ECDN is capable of (1) specifying the conditional distribution of precipitation at each site; (2) modeling occurrence and amount of precipitation simultaneously; (3) reproducing observed spatial relationships between sites; (4) randomly generating synthetic precipitation series; and (5) predicting precipitation amounts in excess of those in the observational record. The ECDN model is applied to two downscaling problems: the first is a benchmark precipitation downscaling task previously evaluated by other modeling groups; the second is a multi-site precipitation dataset from British Columbia, Canada. Results suggest that the ECDN approach is capable of generating spatially and temporally realistic precipitation series that are suitable for use as inputs to hydrological models or to spatial interpolation schemes. http://precedings.nature.com/documents/446/version/1 oai:nature.com:10.1038/npre.2007.446.1 http://dx.doi.org/10.1038/npre.2007.446.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.413.2 2007-07-13T16:35:05Z neuroscience evolutionary-biology

Roots and Emergence of Cognition in Evolution 2007-07-12T23:44:39Z Walter Riofrio Neuroscience Evolutionary Biology Trying to understand when and how the cognitive phenomena arise in evolution continues being a hard problem of confronting. One important task is to find the ways in which we will be able to arrive at those explanations that will enable us to understand how living beings put together perceived sensory information as well as how they represent it. In this presentation, we address some conceptual questions involved in the relationships between sensorial information perceived by brains and its representational capacities. 
 http://precedings.nature.com/documents/413/version/2 oai:nature.com:10.1038/npre.2007.413.2 http://dx.doi.org/10.1038/npre.2007.413.2 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.459.1 2007-07-16T05:09:59Z biotechnology ecology genetics microbiology bioinformatics

Concurrent Acquisition of a Single Nucleotide Polymorphism in Diverse Influenza H5N1 Clade 2.2 Sub-clades 2007-07-14T11:45:45Z Henry L. Niman Bruce R. Boynton Biotechnology Ecology Genetics & Genomics Microbiology Bioinformatics Highly pathogenic Influenza A H5N1 was first identified in Guangdong Province in 1996, followed by human cases in Hong Kong in 1997 1,2. The number of confirmed human cases now exceeds 300, and the associated Case Fatality Rate exceeds 60% 3. The genetic diversity of the serotype continues to increase. Four distinct clades or sub-clades have been linked to human cases 4-7. The gradual genetic changes identified in the sub-clades have been attributed to copy errors by viral encoded polymerases that lack an editing function, thereby resulting in antigenic drift 8. We report here the concurrent acquisition of the same polymorphism by multiple, genetically distinct, clade 2.2 sub-clades in Egypt, Russia, and Ghana. These changes are not easily explained by the current theory of “random mutation” through copy error, and are more easily explained by recombination with a common source. This conclusion is supported by additional polymorphisms shared by clade 2.2 isolates in Egypt and Germany. http://precedings.nature.com/documents/459/version/1 oai:nature.com:10101/npre.2007.459.1 http://hdl.handle.net/10101/npre.2007.459.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.466.1 2007-07-16T09:27:49Z genetics bioinformatics

Biological networks and epistasis in genome-wide association studies 2007-07-16T12:12:46Z Mathieu Emily Leif Schauser Thomas Mailund Mikkel H. Schierup Genetics & Genomics Bioinformatics Over the last few years, technological improvements have made possible the genotyping of hundreds of thousands of SNPs, enabling whole-genome association studies. The first genome-wide association studies have recently been completed to detect causal variant for complex traits. Although increasing evidence suggests that interaction between loci, such as epistasis between two loci, should be considered, most of these studies proceed by considering each SNP independently. One reason for this choice is that looking at all pairs of SNPs increases dramatically the number of tests (approximatively 50 billions of tests for a 300,000 SNPs data set) that faces with computational limitation and strong multiple testing correction.
We proposed to reduce the number of tests by focusing on pairs of SNPs that belong to genes known to interact in some metabolic network. Although some interactions might be missed, these pairs of genes are good candidates for epistasis. Furthermore the use of protein interaction databases (such as the STRING database) may reduce the number of tests by a factor of 5,000.
Results using this approach will be presented on simulated data sets and on public data sets.
 http://precedings.nature.com/documents/466/version/1 oai:nature.com:10.1038/npre.2007.466.1 http://dx.doi.org/10.1038/npre.2007.466.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.459.2 2007-07-23T13:45:43Z biotechnology ecology genetics microbiology bioinformatics

Concurrent Acquisition of a Single Nucleotide Polymorphism in Diverse Influenza H5N1 Clade 2.2 Sub-clades 2007-07-16T12:46:29Z Henry L. Niman Bruce R. Boynton Biotechnology Ecology Genetics & Genomics Microbiology Bioinformatics Highly pathogenic Influenza A H5N1 was first identified in Guangdong Province in 1996, followed by human cases in Hong Kong in 1997. The number of confirmed human cases now exceeds 300, and the associated Case Fatality Rate exceeds 60%. The genetic diversity of the serotype continues to increase. Four distinct clades or sub-clades have been linked to human cases. The gradual genetic changes identified in the sub-clades have been attributed to copy errors by viral encoded polymerases that lack an editing function, thereby resulting in antigenic drift. We report here the concurrent acquisition of the same polymorphism by multiple, genetically distinct, clade 2.2 sub-clades in Egypt, Russia, and Ghana. These changes are not easily explained by the current theory of “random mutation” through copy error, and are more easily explained by recombination with a common source. This conclusion is supported by additional polymorphisms shared by clade 2.2 isolates in Egypt and Germany. http://precedings.nature.com/documents/459/version/2 oai:nature.com:10101/npre.2007.459.2 http://hdl.handle.net/10101/npre.2007.459.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.425.2 2007-07-17T13:56:37Z bioinformatics

Examining the uses of shared data 2007-07-17T17:47:33Z Heather A. Piwowar Douglas B. Fridsma Bioinformatics Background
 Many initiatives and repositories exist to encourage the sharing of research data, and thousands of microarray gene expression datasets are publicly available. Many studies reuse this data, but it is not well understood which datasets are reused and for what purpose.

 Materials and Methods
 We trained a machine-learning algorithm to automatically classify full-text gene expression microarray studies into two classes: those that generated original microarray data (n=900) and those which only reused data (n=250). We then compared the Medical Subject Heading (MeSH) terms of two classes to identify MeSH topics which were over- or under-represented by publications with reused data.

 Results
 Studies on humans, mice, chordata, and invertebrates were equally likely to be conducted using original or shared microarray data, whereas shared data was used in a relatively high proportion of studies involving fungi (odds ratio (OR)=2.4), and a relatively low proportion involving rats, bacteria, viruses, plants, or genetically-altered or inbred animals (OR<0.05). Unsurprisingly, when we looked at Major MeSH terms to represent the primary purpose of the studies, statistical and computational methods clearly dominated. The only biomedical topics with a relatively high proportion of data reuse Major MeSH terms were Promoter Regions, Evolution, and Protein Interaction Mapping.

 Discussion
 Identifying areas of particularly successful microarray data reuse—such as Saccharomyces cerevisiae datasets and studies of promoter regions and evolution—can highlight best practices to be used when developing research agendas, tools, standards, repositories, and communities in areas which have yet to receive major benefits from shared data.
 http://precedings.nature.com/documents/425/version/2 oai:nature.com:10.1038/npre.2007.425.2 http://dx.doi.org/10.1038/npre.2007.425.2 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.478.1 2007-07-18T05:18:26Z ecology

Phyloclimatic Modelling Can Estimate Ancestral Areas 2007-07-18T08:08:44Z Chris Yesson Alastair Culham Ecology Ancestral area selection is traditionally based on geographic patterns analyzed alongside phylogenetic data. The approach assumes consistent climate and will only select areas from within present day distributions. The combination of observed distribution and inferred climate preferences have been used to determine the potential distribution of species in the past, present and future. The heritability of environmental niches, based on climate preferences, has been demonstrated, and ancestral niches have been reconstructed using phylogenetic techniques. These techniques can be combined to estimate ancestral areas. Ancestral area selection via environmental preference differs from traditional methods, as areas which are outside the current observed distribution can be selected if they are environmentally suitable. We present an example using the carnivorous plants Drosera (Droseraceae). We reconstruct the climatic preferences of lineages to model ancestral environmental niches. These ancestral niches are explored to determine the limits of distribution within contemporaneous palaeo-climate scenarios suggested by a temporally calibrated phylogeny. The patterns of palaeo-climate support a restricted Southern Australian distribution that offers a more plausible explanation of the current centre of diversity in South-Western Australia than do models based only on present day climates. http://precedings.nature.com/documents/478/version/1 oai:nature.com:10.1038/npre.2007.478.1 http://dx.doi.org/10.1038/npre.2007.478.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.425.3 2007-07-18T13:26:38Z bioinformatics

Examining the uses of shared data 2007-07-18T15:15:26Z Heather A. Piwowar Douglas B. Fridsma Bioinformatics Does your research area re-use shared datasets?
* Re-using data has many benefits, including research synergy and efficient resource use
* Some research areas have tools, communities, and practices which facilitate re-use
* Identifying these areas will allow us to learn from them, and apply the lessons to areas which underutilize the sharing and re-purposing of scientific data between investigators

 Which datasets?
This preliminary analysis examines the re-use of microarray gene expression datasets. Thousands of microarray gene expression datasets have been deposited in publicly available databases. 
Many studies reuse this data, but it is not well understood for what purposes. Here, we examined all publications found in PubMed Central on April 1, 2007 whose full-text contained the phrases “microarray” and “gene expression” to find studies which re-used microarray data.

 How did we identify re-use?
We developed prototype machine-learning classifiers to identify a) studies containing original microarray data (n=900) and b) studies which instead re-used microarray data (n=250). Preprocessing (Python NLTK) extracted manually-selected keyword frequencies from the full-text publications as features for a Support Vector Machine (SVMlite). The classifier was trained and tested on a manually-labeled set of documents (PLoS articles prior to January 2007 containing the word “microarray,” n=200).

 How did we identify patterns of re-use?
We compared the Medical Subject Heading (MeSH) of the two classes to estimate the odds that a specific MeSH term would be used given all studies with original microarray data, compared to the odds of the same term describing studies with re-used data. Terms were truncated to comparable levels in the MeSH hierarchy.

 Results
Publications with original vs. re-used microarray data have different distributions of MeSH terms (Figure 1), and occur in different proportions across various journals (Figure 2).
 Microarray data source (original vs. re-used) did not affect the odds of a study focusing on humans, mice, or invertebrates, whereas publications with re-used data did involve a relatively high proportion of studies involving fungi (odds ratio (OR)=2.4), and a relatively low proportion involving rats, bacteria, viruses, plants, or genetically-altered or inbred animals (OR<0.5) compared to publications with original data. 
 Trends in odds ratios of MeSH terms for other attributes can be seen in Figure 3.

 Hope
Although not all research topics can be addressed by re-using existing data, many can. Identifying areas with frequent re-use can highlight best practices to be used when developing research agendas, tools, standards, repositories, and communities in areas which have yet to receive major benefits from shared data. 

 Future Work
We plan to refine our tool for identifying studies which re-use data, and continue studying and measuring re-use and reusability. http://precedings.nature.com/documents/425/version/3 oai:nature.com:10.1038/npre.2007.425.3 http://dx.doi.org/10.1038/npre.2007.425.3 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.508.1 2007-07-26T05:20:44Z ecology

Functional aspects of titanosaur osteoderms 2007-07-21T03:05:46Z Thiago S. Marinho Ecology Though titanosaur osteoderms are not common findings, these elements are recorded widely in Gondwana and part of Laurasia. This assembly known by the date offers few resources for studies on the ecology of this group of dinosaurs. Recently, some eggs bearing titanosaur embryos with preserved skin, from Patagonia, Argentina, may shed some light on the function and disposition pattern of these dermic bones. Some of the skin patches associated with the titanosaur embryos show two distinct patterns of tuberosities: a longitudinal row and rosettes, both composed of closely attached tuberosities. These tuberosities do not seem to be ossified, but this might be due to the ontogenetic stage of the titanosaurs. Here we propose that these tuberosities might have been ossified in later ontogenetic stages, and then turning into real osteoderms providing physical defence for the juvenile titanosaurs. Amongst the remains of large titanosaurs like _Mendozasaurus neguyelap_ some osteoderms were recovered, but it is contrasting small to the animal when compared to other dinosaurs. These bones would not provide real defensive advantage to an adult titanosaur as they are small and also have a very spongy internal structure. This apparent fragility also may be the reason that few titanosaur osteoderms have been preserved. In comparison, the tuberosity of a young titanosaur is much larger than an adult osteoderm and its body armor would be much more effective against small predators like notosuchian crocodyliforms and small theropods. And if the titanosaur osteoderms are originated from the embryo’s tuberosities, the disposition of these elements in an adult animal would be very distant to each other. The calcium reserve may be considered as functional for an adult titanosaur though. http://precedings.nature.com/documents/508/version/1 oai:nature.com:10.1038/npre.2007.508.1 http://dx.doi.org/10.1038/npre.2007.508.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.553.1 2007-07-27T09:41:02Z biotechnology ecology genetics microbiology bioinformatics

H5N1 Clade 2.2 Polymorphism Tracing Identifies Influenza Recombination and Potential Vaccine Targets 2007-07-27T11:41:17Z Henry L. Niman Magdi D. Saad Bruce R. Boynton Jeffery Tjaden Kenneth C. Earhart Moustafa M. Mansour Nasr M. ElSayed A I. Nayei A A. Abdelghani Hala M. Essmat Elassai M. Labib E Ayoub Mona M. Aly A-SA Arafa Marshall R. Monteville Biotechnology Ecology Genetics & Genomics Microbiology Bioinformatics Highly pathogenic Influenza A H5N1 was first identified in Guangdong Province in 1996, followed by human cases in Hong Kong in 1997 1. The number of confirmed human cases now exceeds 300 and the associated Case Fatality Rate exceeds 60% 2. The genetic diversity of the serotype continues to increase. Four distinct clades or sub-clades have been linked to human cases 3.4. The gradual genetic changes identified in the sub-clades have been attributed to copy errors by viral encoded polymerases that lack an editing function, thereby resulting in antigenic drift 5. We traced polymorphism acquisition in Clade 2.2 sequences. We report here the concurrent acquisition of the same polymorphism by multiple, genetically distinct, Clade 2.2 sub-clades in Egypt, Russia and Ghana. These changes are not easily explained by the current theory of “random mutation” through copy error, and are more easily explained by recombination with a common source. This conclusion is supported by additional polymorphisms shared by Clade 2.2 isolates in Egypt, Nigeria and Germany including aggregation of regional polymorphisms from each of these areas into a single Nigerian human hemagglutinin gene. http://precedings.nature.com/documents/553/version/1 oai:nature.com:10.1038/npre.2007.553.1 http://dx.doi.org/10.1038/npre.2007.553.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.579.1 2007-08-09T07:15:12Z ecology genetics

The saltational model for the dawn of H. sapiens, chin, adolescence phase, complex language and modern behavior 2007-08-01T10:23:01Z Omer Faruk NOYAN Sahin CAKIR Ecology Genetics & Genomics A new model may contribute to resolve the origin problem of H. sapiens. According to our new viewpoint, Neandertals were neither one of our direct ancestors nor a different species. Their origin was not in Europe 150-200 or 300 thousand years ago. As for the origin of H. sapiens, it was neither in Africa roughly 2 million years ago nor roughly 200 thousand years ago. In other words, both the Multiregional model and the recent African origin model seem wrong. Our own species arose in the Middle East approximately 150 thousand years ago and split into two subspecies: Moderns and Neandertals. Rapid and radial expansion of H. sapiens from the origin implies a revolution (see Figure 1). Complex language, modern behavior and even adolescence phase plus chin might be included into the revolution. This possibility seems consistent with the data and could also be tested via; 1-the origin of complex language based on the modern human form of FOXP2 gene 2-the origin of adolescence or adolescent growth spurt 3- the genetic origin of the Flores hobbits. If all of these three origins appeared in the Levant about 150 thousand years ago then our model is true in all aspects. This speciation seems an unexpected revolution or macroevolution occured in several thousand years. The last pre-sapiens hominids may be extinct due to OIS 6 namely without replacement by sapiens. http://precedings.nature.com/documents/579/version/1 oai:nature.com:10101/npre.2007.579.1 http://hdl.handle.net/10101/npre.2007.579.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.595.1 2007-08-03T15:23:55Z earth-and-environment

Visualization of and Access to CloudSat Vertical Data through Google Earth 2007-08-03T04:17:05Z Aijun Chen Gregory Leptoukh Liping Di Steven Kempler Christopher Lynnes Earth & Environment Online tools, pioneered by the Google Earth (GE), are facilitating the way in which scientists and general public interact with geospatial data in real three dimensions. However, even in Google Earth, there is no method for depicting vertical geospatial data derived from remote sensing satellites as an orbit curtain seen from above. Here, an effective solution is proposed to automatically render the vertical atmospheric data on Google Earth. The data are first processed through the Giovanni system, then, processed to be 15-second vertical data images. A generalized COLLADA model is devised based on the 15-second vertical data profile. Using the designed COLLADA models and satellite orbit coordinates, a satellite orbit model is designed and implemented in KML format to render the vertical atmospheric data in spatial and temporal ranges vividly. The whole orbit model consists of repeated model slices. The model slices, each representing 15 seconds of vertical data, are placed on the CloudSat orbit based on the size, scale, and angle with the longitude line that are precisely and separately calculated on the fly for each slice according to the CloudSat orbit coordinates. The resulting vertical scientific data can be viewed transparently or opaquely on Google Earth. Not only is the research bridged the science and data with scientists and the general public in the most popular way, but simultaneous visualization and efficient exploration of the relationships among quantitative geospatial data, e.g. comparing the vertical data profiles with MODIS and AIRS precipitation data, becomes possible. http://precedings.nature.com/documents/595/version/1 oai:nature.com:10.1038/npre.2007.595.1 http://dx.doi.org/10.1038/npre.2007.595.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.631.1 2007-08-07T12:35:12Z chemistry pharmacology plant-biology

Biological Activities of Extracts from Sumac (Rhus spp.): A Review 2007-08-06T22:12:15Z Sierra Rayne Giuseppe Mazza Chemistry Pharmacology Plant Biology Sumac is the common name for a genus (Rhus) that contains over 250 individual species of flowering plants in the family Anacardiaceae. These plants are found in temperate and tropical regions worldwide, often grow in areas of marginal agricultural capacity, and have a long history of use by indigenous peoples for medicinal and other uses. The research efforts on sumac extracts to date indicate a promising potential for this plant family to provide renewable bioproducts with the following reported desirable bioactivities: antifibrogenic, antifungal, antiinflammatory, antimalarial, antimicrobial, antimutagenic, antioxidant, antithrombin, antitumorigenic, antiviral, cytotoxic, hypoglycaemic, and leukopenic. As well, the bioactive components can be extracted from the plant material using environmentally benign solvents that allow for both food and industrial end-uses. The favorable worldwide distribution of sumac also suggests that desirable bioproducts may be obtained at source, with minimal transportation requirements from the source through processing to end consumer. However, previous work has focussed on only a few members of this large plant family. In addition, not all of the species studied to date have been fully characterized for potential bioactive components and bioactivities. Thus, there remains a significant research gap spanning the range from lead chemical discovery through process development and optimization in order to better understand the full potential of the Rhus genus as part of global green technology based bioproduct and bioprocess research programs. http://precedings.nature.com/documents/631/version/1 oai:nature.com:10101/npre.2007.631.1 http://hdl.handle.net/10101/npre.2007.631.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.632.1 2007-08-07T08:42:55Z biotechnology chemistry

Trichoderma reesei derived cellulase activity in three N,N-dimethylethanolammonium akylcarboxylate ionic liquids 2007-08-06T23:27:58Z Sierra Rayne Giuseppe Mazza Biotechnology Chemistry The activity and denaturation extent of cellulase from Trichoderma reesei (E.C. # 3.2.1.4) was investigated in three representative N,N-dimethylethanolammonium akylcarboxylate ionic liquids. Significant cellulase activity and absence of enzyme unfolding was found in all concentrations of N,N-dimethylethanolammonium acetate (DMEAA), including the pure liquid. Activities in 20% and 40% (v/v) solutions of DMEAA were equal to citrate buffer controls. Lower enzymatic activities and denaturation were observed in solutions of the corresponding formate and octanoate ionic liquids, although cellulose hydrolysis still proceeded at a substantial rate. The results provide the first proof-of-principle that cellulose can be enzymatically hydrolyzed in the presence of high ionic liquid concentrations. http://precedings.nature.com/documents/632/version/1 oai:nature.com:10101/npre.2007.632.1 http://hdl.handle.net/10101/npre.2007.632.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.636.1 2007-08-07T12:36:52Z biotechnology chemistry pharmacology earth-and-environment

High-Value Phytochemicals from Grape Cane Waste: Potential Value-Added Viticultural Sources of Trans-Resveratrol and Trans-e-Viniferin with Medicinal and Anti-Phytopathogenic Applications 2007-08-07T01:49:05Z Sierra Rayne Biotechnology Chemistry Pharmacology Earth & Environment Grape canes as agricultural waste from commercial viticultural activities represent a potentially important source of the well-known medicinal and anti-phytopathogenic stilbene compounds trans-resveratrol and trans-e-viniferin. Reports in the literature suggest that concentrations of these compounds range up to 5 mg/g dw and 2 mg/g dw, respectively, and can be quantitatively extracted from the cane residue using low-cost, environmental benign, and non-toxic aqueous alcoholic solvent systems such as ethanol:water mixtures. With current commercial values of these compounds between US$2,000 to US$3,000 per kg, established stilbene yields from cane waste could represent an agricultural coproduct valued at US$2,000 to US$3,000 per hectare of production. At the present worldwide wine grape production of 8,000,000 ha, the extraction of trans-resveratrol and trans-e-viniferin from grape cane waste would have an estimated global economic value of >$30 billion. http://precedings.nature.com/documents/636/version/1 oai:nature.com:10101/npre.2007.636.1 http://hdl.handle.net/10101/npre.2007.636.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.637.1 2007-08-07T08:56:40Z chemistry earth-and-environment plant-biology

Rapid Dissolution of Lignocellulosic Plant Materials in an Ionic Liquid 2007-08-07T03:39:23Z Sierra Rayne Giuseppe Mazza Chemistry Earth & Environment Plant Biology Concerns regarding the non-renewable nature of, and pollution from, petroleum derived energy and commercial products has led to the concept of a biomass economy. As part of this vision for a society based on sustainable biomaterials, proposed biorefineries need to tackle the challenges of taking a wide diversity of raw biomass and rapidly and effectively transforming it into functionalizable platform molecules that can be derivatized into industrial and consumer products, or converted into biofuels. A substantial research effort is underway focussed on degrading biomass into smaller constituents using a variety of physical, chemical, and biological processes. One promising technology for the solubilization of biomass is ionic liquids (ILs), which has received considerable attention as a medium for efficient solubilization of a variety of materials. ILs also allow fractional separation when combined with solvent extraction (conventional, and green technologies such as supercritical CO2), precipitation, and adsorption/absorption methods, and to conduct a wide range of chemical reactions using thermal, electrochemical, photochemical, and biocatalytic processes. As a potential pretreatment technology for the biorefineries of the future, we report herein the first rapid dissolution of a range of coniferous and deciduous woods and grassy lignocellulosic plant materials in an IL using microwave radiation. http://precedings.nature.com/documents/637/version/1 oai:nature.com:10101/npre.2007.637.1 http://hdl.handle.net/10101/npre.2007.637.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.638.1 2007-08-10T08:58:06Z chemistry ecology earth-and-environment

Concentrations of Polychlorinated Biphenyls (PCBs), Polychlorinated Dibenzo-p-dioxins and Furans (PCDD/Fs), and Polybrominated Diphenyl Ethers (PBDEs) as Functions of Sample Depth in Killer Whale (Orcinus orca) Blubber 2007-08-07T03:44:17Z Michael G. Ikonomou Sierra Rayne Norman F. Crewe Chemistry Ecology Earth & Environment Concentrations of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), and polybrominated diphenyl ethers (PBDEs) were examined as a function of depth in killer whale (Orcinus orca) blubber samples. Lipid-normalized concentrations of PCBs, PCDD/Fs, and PBDEs did not display significant variation with depth in three distinct blubber layers (outer, central, and inner). Significantly more variation in contaminant concentrations were observed with depth on a wet weight basis for the killer whale sample. The current study indicates that non-invasive microdart biopsy sampling methods commonly used for monitoring contaminants in marine mammals yield representative details on contaminant burdens for chlorinated and brominated aromatic compounds in marine mammal blubber, regardless of the quantity and type of blubber sampled, provided that lipid normalization is performed on resulting analytical determinations. http://precedings.nature.com/documents/638/version/1 oai:nature.com:10101/npre.2007.638.1 http://hdl.handle.net/10101/npre.2007.638.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.553.2 2007-08-07T16:18:58Z biotechnology ecology genetics microbiology bioinformatics

H5N1 Clade 2.2 Polymorphism Tracing Identifies Influenza Recombination and Potential Vaccine Targets 2007-08-07T17:32:07Z Henry L. Niman Magdi D. Saad Elassai M. Labib E Ayoub Mona M. Aly A-SA Arafa Marshall R. Monteville Bruce R. Boynton Jeffery Tjaden Kenneth C. Earhart Moustafa M. Mansour Nasr M. ElSayed A I. Nayei A A. Abdelghani Hala M. Essmat Biotechnology Ecology Genetics & Genomics Microbiology Bioinformatics Highly pathogenic Influenza A H5N1 was first identified in Guangdong Province in 1996, followed by human cases in Hong Kong in 1997 1. The number of confirmed human cases now exceeds 300 and the associated Case Fatality Rate exceeds 60% 2. The genetic diversity of the serotype continues to increase. Four distinct clades or sub-clades have been linked to human cases 3.4. The gradual genetic changes identified in the sub-clades have been attributed to copy errors by viral encoded polymerases that lack an editing function, thereby resulting in antigenic drift 5. We traced polymorphism acquisition in Clade 2.2 sequences. We report here the concurrent acquisition of the same polymorphism by multiple, genetically distinct, Clade 2.2 sub-clades in Egypt, Russia and Ghana. These changes are not easily explained by the current theory of “random mutation” through copy error, and are more easily explained by recombination with a common source. This conclusion is supported by additional polymorphisms shared by Clade 2.2 isolates in Egypt, Nigeria and Germany including aggregation of regional polymorphisms from each of these areas into a single Nigerian human hemagglutinin gene. http://precedings.nature.com/documents/553/version/2 oai:nature.com:10.1038/npre.2007.553.2 http://dx.doi.org/10.1038/npre.2007.553.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.651.1 2007-08-08T12:02:56Z molecular-cell-biology

Extragenic Suppression analysis of TS mutations using Sec61p 2007-08-08T15:16:36Z Sterling Smith Molecular Cell Biology During synthesis, secretory and membrane proteins are cotranslationally translocated into the lumen of the endoplasmic reticulum through an aqueous gated channel. Proper folding, degradation, and transport of many polypeptides depend on a diverse set of helper proteins termed chaperone. I hypothesize that
Sec 61p is a membrane chaperone, which actively directs membrane protein folding.
 http://precedings.nature.com/documents/651/version/1 oai:nature.com:10.1038/npre.2007.651.1 http://dx.doi.org/10.1038/npre.2007.651.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.655.1 2007-08-08T17:08:11Z earth-and-environment

Electron Microprobe Chemical Dating of Uraninite as a Reconnaissance Tool for Leucogranite Geochronology 2007-08-08T20:33:30Z Jose M. Hurtado Nilanjan Chatterjee Jahandar Ramezani Kip V. Hodges Samuel A. Bowring Earth & Environment We suggest that electron microprobe techniques may be employed to date Tertiary samples of uraninite (UO~2~), which can contain very high concentrations of radiogenic Pb after only a few million of years of U and Th decay. Although uraninite is regarded as a rare accessory mineral, it is relatively abundant in leucogranitic rocks such as those found in the Himalayan orogen. We apply the U-Th-total Pb electron microprobe chemical dating method to a uraninite crystal from a ca. 18.3 Ma dike of the Mugu granite from the Upper Mustang region of central Nepal. With this technique, we calculate a mean chemical date that is consistent with isotope-dilution thermal ionization mass spectrometry (ID-TIMS) U-Pb dates obtained from seven other uraninite grains and a monazite crystal from the same sample. Electron microprobe chemical dating yields results that typically will be an order of magnitude less precise than conventional dates: in the specific case of the Mugu granite, single point chemical dates each have ca. 1.5 Ma 2[sigma] (95%) confidence level uncertainties. However, the mean chemical date of 15 point analyses of the crystal we study has a 2SE (2 standard error) uncertainty of ca. 400 ka, comparable to uncertainties obtained with ID-TIMS. These results show that electron microprobe chemical dating of uraninite has substantial promise as a reconnaissance tool for the geochronology of young granitic rocks. The electron microprobe work also reveals substantial chemical complexity within uraninite that must be taken into account. The analyzed crystal displays a texturally and chemically distinctive core and rim that suggests episodic growth. Concentration gradients in U, Th, and Y across the boundary imply diffusive modification. We estimate the diffusivity of U, Th, and Y in uraninite at ca. 700 °C to be > 10-7 cm2 s-1. In contrast, Pb shows no distinctive concentration gradient across the core-rim boundary, implying that Pb has a much higher diffusivity in uraninite than U, Th, or Y. We estimate that Pb loss of as much as ca. 8.9% has occurred in the uraninite grains we analyzed by ID-TIMS. http://precedings.nature.com/documents/655/version/1 oai:nature.com:10101/npre.2007.655.1 http://hdl.handle.net/10101/npre.2007.655.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.659.1 2007-08-09T07:03:25Z earth-and-environment

Ecological control on micro-ornamentation of conodont elements 2007-08-09T05:41:44Z Andrey V. Zhuravlev Earth & Environment Conodonts are considered now as specific group of early Chordata or even Vertebrata. Fifteen tooth-like conodont elements of seven morphological types compose the oral apparatus of conodonts. The elements demonstrate complex morphology. All the elements bear polygonal micro-ornamentation. The ornamentation is considered as representing imprints of the epithelium cells. Ecological dependencies of the cell sizes are known for some recent organisms.
The maximum cell sizes are characteristic of optimal environmental conditions. Thus, one can supposes that decreasing in cell imprint size in the conodonts marks disturbance in water temperature or/and oxygen content.
 http://precedings.nature.com/documents/659/version/1 oai:nature.com:10101/npre.2007.659.1 http://hdl.handle.net/10101/npre.2007.659.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.663.1 2007-08-10T09:00:06Z molecular-cell-biology

Synergistic Induction of NR4A Orphan Nuclear Receptors by LPS and cAMP in Murine Macrophage Cells 2007-08-09T12:19:21Z Harish Shandilya Sidney M. Morris Molecular Cell Biology Although NR4A orphan nuclear receptors have been implicated in inflammatory gene expression and atherosclerosis, there is little information regarding their regulation by combinations of stimuli likely to be found in vivo, such as LPS and inducers of cAMP. LPS rapidly induced Nur77 and NOR1 mRNAs but had little effect on expression of Nurr1 mRNA. All three NR4As were rapidly induced by 8-bromo-cAMP and remained elevated for at least 8 h. Maximum induction of NOR1 by 8-bromo-cAMP was much greater than with LPS, but maximum induction of Nur77 was similar with both agents. Whereas Nurr1 mRNA had very little response to LPS, it was strongly induced by 8-bromo-cAMP, and Nurr1 mRNA levels remained elevated for at least 20 h. The combination of 8-bromo-cAMP and LPS acted synergistically to strongly induce NOR1 and Nur77, whereas LPS partially inhibited the induction of Nurr1 by 8-bromo-cAMP. Nurr1 protein levels correlated with Nurr1 mRNA levels but exhibited slower response kinetics. In summary, the NR4A receptors did not respond identically to individual stimuli or to combinations of stimuli. In particular, the magnitude of the responses to combinations of stimuli was quite different than to individual stimuli. Thus, NR4A receptor expression and the resulting functional consequences are more complex than appreciated from previous studies that evaluated regulation of NR4A expression by single stimuli. http://precedings.nature.com/documents/663/version/1 oai:nature.com:10.1038/npre.2007.663.1 http://dx.doi.org/10.1038/npre.2007.663.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.670.1 2007-08-13T05:14:24Z biotechnology bioinformatics

DNALinux Virtual Desktop Edition 2007-08-09T22:11:02Z Sebastian Bassi Virginia V. C. Gonzalez Biotechnology Bioinformatics The new version of DNALinux (VDE) is presented. DNALinux VDE is a departure from traditional distributions since it uses a virtual machine to bundle together the operating system and bioinformatics applications. The main advantage of this approach is that a virtualized environment doesn't affect a installed system. With a virtual machine a Linux system can be run under a Windows system, provided that the virtual machine player is installed. The included programs are listed and specifications to add more programs are explained. We believe that DNALinux could be used as a standardized virtual machine for learning, using, developing and testing bioinformatics applications. http://precedings.nature.com/documents/670/version/1 oai:nature.com:10.1038/npre.2007.670.1 http://dx.doi.org/10.1038/npre.2007.670.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.682.1 2007-08-24T19:07:00Z genetics

Picturing the genetic code 2007-08-10T22:06:58Z A.W.F. Edwards Genetics & Genomics The 64 codons of the genetic code are arranged on a six-set Edwards-Venn diagram in such a way that the amino-acids are advantageously displayed. http://precedings.nature.com/documents/682/version/1 oai:nature.com:10.1038/npre.2007.682.1 http://dx.doi.org/10.1038/npre.2007.682.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.684.1 2007-08-13T05:11:49Z ecology earth-and-environment

Abundance and Composition of Zooplankton (Copepoda, Cladocera, Rotifera) in Lake Taal: Potential Impact of Intensive Size-Selective Predation by the Freshwater Sardine, Sardinella tawilis (Herre 1927) 2007-08-11T05:47:54Z Rey Donne Papa Roberto Pagulayan Alicia Ely Pagulayan Ecology Earth & Environment Zooplankton are considered to be important members of the lake ecosystem. The abundance and composition of which are due to several factors, for example, the impact of intensive size-selective predation by planktivorous fishes residing in the lake. In this study, the abundance and composition of zooplankton found in the vicinity of Isla Napayun - a known fishing ground of the freshwater sardine, Sardinella tawilis (Herre 1927) was analyzed using samples taken from vertical plankton tows from the 10 and 20 m depths in 2 sampling sites from the said area. These were then compared with the stomach contents of S. tawilis taken during the same period. Results show that there were 4 genera of Copepoda, 4 genera of Cladocera and 2 genera of Rotifera found in the plankton tows that were analyzed. Of these, the nauplius larvae of the copepods were noted to be the most abundant followed by the rotifer Brachionus spp. Analysis of the stomach contents of the collected S. tawilis samples revealed a zooplankton diet that was composed of 90% Copepoda with the remaining 10% being made up of the Cladocera and Rotifera. These results indicate that small-bodied organisms dominate the lake. This is indicative of intensive size-selective predation by the S. tawilis on the zooplankton population of the area. This is further validated by the high preference of S. tawilis for Copepoda, which is the largest of the 3 groups (in terms of size) in the samples that were analyzed in spite of the fact that small-bodied zooplankton dominate the zooplankton community during the entire sampling period. The zooplankton found in this particular area of Lake Taal has been observed to be highly influenced by intensive size selective preference of planktivores such as the S. tawilis for bigger zooplankton. http://precedings.nature.com/documents/684/version/1 oai:nature.com:10.1038/npre.2007.684.1 http://dx.doi.org/10.1038/npre.2007.684.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.689.1 2007-08-15T10:06:10Z chemistry earth-and-environment

Sustainability and Environmental Chemistry in Semi-Arid/Arid Regions: A Unique Research Opportunity with Global Implications 2007-08-12T05:50:08Z Sierra Rayne Chemistry Earth & Environment Dr. Sierra Rayne will be speaking on the interplay of sustainability and environmental chemistry in semi-arid and arid regions worldwide. Drawing on his previous, current, and proposed research on organic and inorganic contaminants in aquatic systems, Dr. Rayne will illustrate the importance of multidisciplinary and interdisciplinary approaches towards tackling environmental problems. A key element of his work is looking at chemical dynamics in environmental matrices, and in particular, photochemically generated reactive intermediates and their impact on biological systems and net ecosystem functions. Semi-arid/arid regions also offer unique opportunities to focus on the role of photochemistry in the biogeochemical cycling of oxyanion-forming heavy metals such as arsenic, molybdenum, selenium, and uranium (among others). Given the importance of semi-arid/arid regions in hosting major mineral deposits, multidisciplinary environmental chemistry research can also help make contributions towards sustainability in the worldwide mining industry. These fields offer great opportunities for researchers and students interested in semi-arid/arid landscapes, and understanding the role and impact of these regions on global contaminant fluxes is at the core of Dr. Rayne’s program. http://precedings.nature.com/documents/689/version/1 oai:nature.com:10.1038/npre.2007.689.1 http://dx.doi.org/10.1038/npre.2007.689.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.690.1 2007-08-18T07:24:53Z chemistry earth-and-environment

Chlorinated Diphenyl Ethers in Sediments, Biota, and the Water Column from Coastal British Columbia, Canada 2007-08-12T06:11:50Z Sierra Rayne Ikonomou G. Michael Chris Garrett Chemistry Earth & Environment Polychlorinated diphenyl ethers (PCDEs) are impurities in technical chlorophenol mixtures, are used as dielectric fluids in capacitors and as herbicides, antiseptics, food preservatives, and papers and textiles, and can be formed through the chlorination of organics in water and wastewater streams. Samples from semipermeable membrane devices (SPMDs), sediments, English sole, mussels, and Dungeness crab were collected from urban/industrial and remote sites along the marine coast of British Columbia and analyzed by congener-specific GC-MS analysis for mono- through deca-substituted PCDEs. Higher concentrations in biota and sediments were observed near urban/industrial areas, with evidence for food-chain biomagnification within major harbours. Correlations between size distributions and PCDE levels indicate these hydrophobic contaminants tend to preferentially partition into sediments with higher clay/silt fractions. Multivariate analysis of congener patterns shows distinct PCDE profiles among different species and environmental matrices, and evidence for favoured dechlorination pathways among the most commonly observed congeners in aquatic systems. http://precedings.nature.com/documents/690/version/1 oai:nature.com:10.1038/npre.2007.690.1 http://dx.doi.org/10.1038/npre.2007.690.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.697.1 2007-08-13T09:48:21Z biotechnology genetics bioinformatics plant-biology

Heterogeneity in Ty1-copia group of retroelements in chickpea (Cicer arietinum) genome 2007-08-13T12:32:57Z Manoj K. Rajput Kailash C. Upadhyaya Biotechnology Genetics & Genomics Bioinformatics Plant Biology Retrotransposons constitute a major fraction of plant genomes and these elements may have played a significant role in evolution and sequence organization of genomes. In order to access the diversity of Ty1-copia group of retroelements, reverse transcriptase (RT) sequences were amplified from chickpea genome, using the primers derived from two conserved domains of RT region. Thirty-six RT regions from independent amplicons were cloned and sequenced. On the basis of homology of deduced amino acids, the RT sequences could be grouped into three major families. The intra-family divergence at amino acid level ranges from 2 to 19%. Though intra-family RT sequences were conserved but no two sequences were identical. The results indicate a high degree of heterogeneity among the Ty1-copia group of retroelements from chickpea. It was possible to isolate RT specific sequences from RNA isolated from stressed seedlings, indicating that some of the retroelements may be functional under certain stress conditions. http://precedings.nature.com/documents/697/version/1 oai:nature.com:10101/npre.2007.697.1 http://hdl.handle.net/10101/npre.2007.697.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.716.1 2007-08-14T14:44:55Z neuroscience

The folding fingerprint of visual cortex reveals the timing of human V1 and V2 2007-08-14T18:17:24Z Justin Ales Thom Carney Stanley A. Klein Neuroscience Primate neocortex contains over 30 visual areas. Recent techniques such as functional magnetic resonance imaging (fMRI) have successfully identified many of these areas in the human brain, but have been of limited value for revealing the temporal dynamics between adjacent visual areas, a critical component of understanding visual cognition. The voltages recorded at the scalp, electroencephalography (EEG), is a direct measure of neural activity that reflects the summed activity across all brain areas. Identifying the cortical sources that contribute to the EEG is a difficult problem. We developed an anatomically constrained dipole search method that solves the traditional problems by combining fMRI, EEG and many stimuli that activate small cortical regions. The method provides a means to validate the extracted waveforms. Both V1 and V2 waveforms have similar onset latencies as well as dynamics that can explain previous controversial findings about the responses of these areas. http://precedings.nature.com/documents/716/version/1 oai:nature.com:10101/npre.2007.716.1 http://hdl.handle.net/10101/npre.2007.716.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.734.1 2007-08-15T09:06:42Z chemistry molecular-cell-biology

Solvent Induced Disulfide Bond Formation in 2,5-dimercapto-1,3,4-thiadiazole 2007-08-15T11:01:05Z Palanisamy Kalimuthu Palraj Kalimuthu S. Abraham John Chemistry Molecular Cell Biology Disulfide bond formation is the decisive event in the protein folding to determine the conformation and stability of protein. To achieve this disulfide bond formation in vitro, we took 2,5-dimercapto-1,3,4-thiadiazole (DMcT) as a model compound. We found that disulfide bond formation takes place between two sulfhydryl groups of DMcT molecules in methanol. UV-Vis, FT-IR and mass spectroscopic as well as cyclic voltammetry were used to monitor the course of reaction. We proposed a mechanism for the solvent induced disulfide bond formation on the basis of the results we obtained. http://precedings.nature.com/documents/734/version/1 oai:nature.com:10101/npre.2007.734.1 http://hdl.handle.net/10101/npre.2007.734.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.735.1 2007-08-16T09:50:35Z cancer chemistry molecular-cell-biology pharmacology

Opposite effects of two zinc(II) dithiocarbamates on NF-kB pathway 2007-08-15T11:21:41Z Boris Cvek Zdenek Dvorak Jan Taraba Lukas Muller Radim Vrzal Jitka Ulrichova Cancer Chemistry Molecular Cell Biology Pharmacology Inhibiting nuclear factor-kappaB (NF-kB) activation in anticancer and antiinflammatory therapy is of topical interest. Current research in molecular biology has dramatically advanced in the understanding of the cellular events involved in NF-kB induction. Dithiocarbamates, in particular diethyldithiocarbamate and pyrrolidinedithiocarbamate, have been known and widely used as strong inhibitors of NF-kB signaling pathway for more than ten years. Their activity is frequently thought to be due to chelating of zinc or copper present in serum supplemented in the culture medium. Zinc(II) diethyldithiocarbamate (Et2Zn) and zinc(II) dibenzyldithiocarbamate (Bz2Zn) were prepared by direct synthesis in aqueous millieu. They were structurally characterized by X-ray analysis (solid phase) and mass spectrometry (aqueous conditions). Et2Zn and Bz2Zn both in 20 micromolar concentration were applied to HeLa cells. The status of NF-kB signaling was assessed as nuclear translocation of p65 subunit. Surprisingly, Et2Zn activated NF-kB pathway, while TNF-dependent activation of NF-kB was inhibited by Bz2Zn. Our results are preliminary. http://precedings.nature.com/documents/735/version/1 oai:nature.com:10.1038/npre.2007.735.1 http://dx.doi.org/10.1038/npre.2007.735.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.740.1 2007-08-21T05:37:18Z evolutionary-biology

Evolution of Co-operation When the Strategies are Hidden: The Human Mating Game 2007-08-16T07:28:20Z Milind Watve Anuja Damle Bratati Ganguly Anagha Kale Evolutionary Biology Defection is frequently seen in co-operative systems [1-3]. Game theoretical solutions to stabilize cooperation rely on reciprocity and reputation in iterated games[4-5]. One of the basic requirements for reciprocity or reputation building is that the strategies of players and the resulting payoffs should be open at the end of every interaction. For games in which the strategies and payoffs remain hidden, these stabilizing factors are unlikely to work. We examine the evolution of cooperation for hidden-strategy games using human mating game as an example. Here faithful parenting can be considered as cooperation and extra-pair mating (EPM) or cuckoldry as defection. Cuckoldry may get exposed only occasionally and the genetic benefits of cuckoldry also remain hidden from the players. Along with mate guarding, social policing is enabled in humans by language and gossiping. However, social policing can be invaded by second order free riders. We suggest that opportunistic blackmailing, which is unique to hidden strategy games can act as a keystone strategy in stabilizing co-operation. This can counteract free riding and stabilize policing. A game theoretical model results into a rock - paper – scissor (R-P-S) like situation with no evolutionary stable strategy (ESS). Simulations result into a stable or stably oscillating polymorphism. Obligate monogamy is an essential trait in the co-existence. In a gender difference model too, polymorphism is seen in both genders but with different traits predominating in the two genders. The model explains intra-gender, inter-gender as well as cross cultural variability in mating strategies in humans. http://precedings.nature.com/documents/740/version/1 oai:nature.com:10.1038/npre.2007.740.1 http://dx.doi.org/10.1038/npre.2007.740.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.743.1 2007-08-16T15:53:42Z biotechnology ecology genetics immunology microbiology bioinformatics

Aggregation of Single Nucleotide Polymorphisms in a Human H5N1 Clade 2.2 Hemagglutinin 2007-08-16T16:24:26Z Henry L. Niman Magdi D. Saad Jeffery Tjaden Kenneth C. Earhart Marshall R. Monteville Mona M. Aly Moustafa M. Mansour Nasr El-Sayed Ahmed E. Nayel Ahmed S. Abdelghani Hala M. Esmat Emad M. Labib Ehab A. Ayoub Abdelattar Arafa Gregory A. Raczniak Mensah Agyen-Frempong William K. Ampofo Bruce R. Boynton Biotechnology Ecology Genetics & Genomics Immunology Microbiology Bioinformatics The evolution of H5N1 has attracted significant interest 1-4 due to linkages with avian 5,6 and human infections 7,8. The basic tenets of influenza genetics 9 attribute genetic drift to replication errors caused by a polymerase complex that lacks a proof reading function. However, recent analysis 10 of swine influenza genes identifies regions copied with absolute fidelity for more than 25 years. In addition, polymorphism tracing of clade 2.2 H5N1 single nucleotide polymorphisms identify concurrent acquisition 11 of the same polymorphism onto multiple genetic backgrounds in widely dispersed geographical locations. Here we show the aggregation of regional clade 2.2 polymorphisms from Germany, Egypt, and sub-Sahara Africa onto a human Nigerian H5N1 hemagglutinin (HA), implicating recombination in the dispersal and aggregation of single nucleotide polymorphisms from closely related genomes. http://precedings.nature.com/documents/743/version/1 oai:nature.com:10101/npre.2007.743.1 http://hdl.handle.net/10101/npre.2007.743.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.241.2 2007-08-17T11:43:58Z evolutionary-biology

Systema Naturae. Classification of living things. 2007-08-16T22:37:13Z Alexey Shipunov Evolutionary Biology Original classification of living organisms containing four kingdoms (Monera, Protista, Vegetabilia and Animalia), 60 phyla and 254 classes, is presented. The classification is based on latest available information. http://precedings.nature.com/documents/241/version/2 oai:nature.com:10.1038/npre.2007.241.2 http://dx.doi.org/10.1038/npre.2007.241.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.760.1 2007-08-20T17:14:04Z neuroscience

Meta-Potentiation: Neuro-Astroglial Interactions Supporting Perceptual Consciousness 2007-08-17T19:13:42Z Alfredo Pereira Jr Fábio Augusto Furlan Neuroscience Conscious perceptual processing involves the sequential activation of cortical networks at several brain locations, and the onset of oscillatory synchrony affecting the same neuronal population. How do the earlier activated circuits sustain their excitation to synchronize with the later ones? We call such a sustaining process "meta-potentiation", and propose that it depends on neuro-astroglial interactions. In our proposed model, attentional cholinergic and stimulus-related glutamatergic inputs to astroglia elicit the release of astroglial glutamate to bind with neuronal NMDA receptors containing the NR2B subunit. Once calcium channels are open, slow inward currents activate the CaM/CaMKII complex to phosphorylate AMPA receptors in a population of neurons connected with the astrocyte, thus amplifying the local excitatory pattern to participate in a larger synchronized assembly that supports consciousness. http://precedings.nature.com/documents/760/version/1 oai:nature.com:10101/npre.2007.760.1 http://hdl.handle.net/10101/npre.2007.760.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.792.1 2007-08-22T18:00:48Z chemistry earth-and-environment

The Use of Critical Solution Mixtures for Contaminated Sediments Remediation 2007-08-22T12:26:17Z Tal Golan Zvi Ludmer Elena Ermolenko Neima Brauner Amos Ullmann Chemistry Earth & Environment Using a critical solution mixture, into which chelating agents have been dissolved, resulted in the efficient, rapid and simultaneous removal of both heavy metals and organic pollutants from contaminated sediments. Both heating and cooling across the immiscibility curve and isothermal extraction were investigated. In addition, the extraction yields were compared to those obtained with solution mixtures that do not possess a critical point of miscibility. Extraction yields of the former were superior to those of the latter in the range of relevant pressures (1 atm.) and temperatures. Extraction via heating and cooling across the miscibility curve resulted in the removal of close to 90% of the heavy metals and practically all of the organic contaminants, compared to only about 40% when the extraction was performed isothermally at around 20oC. http://precedings.nature.com/documents/792/version/1 oai:nature.com:10.1038/npre.2007.792.1 http://dx.doi.org/10.1038/npre.2007.792.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.794.1 2007-08-23T15:00:17Z bioinformatics

A science metrics based citation for tagging the biomedical researchers 2007-08-22T16:48:50Z Adeilton Brandao Bioinformatics With the thousands of scientific papers being produced every month, picking an authors name, associate it to a research field and right evaluate his or her performance is in most of times a cumbersome task. I am proposing here that science indexes as h-index, g-index, total citations and published papers could be added to biomedical bibliographic citation in order to create a unique identifier for a given researcher. http://precedings.nature.com/documents/794/version/1 oai:nature.com:10.1038/npre.2007.794.1 http://dx.doi.org/10.1038/npre.2007.794.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.798.1 2007-08-23T11:24:55Z ecology

Computer simulations on the sympatric speciation modes for the Midas cichlid species complex 2007-08-22T21:18:14Z Karen Luz-Burgoa Suzana Moss de Oliveira Jorge de Sá Martins Ecology Cichlid fishes are one of the best model system for the study of evolution of the species. Inspired by them, in this paper we simulated the splitting of a single species into two separate ones via random mutations, with both populations living together in sympatry, sharing the same habitat. We study the ecological, mating and genetic conditions needed to reproduce the polychromatism and polymorphism of three species of the Midas Cichlid species complex. Our results show two scenarios for the A. Citrinellus speciation process, one with and the other without disruptive natural selection. 
In the first scenario, the ecological and genetic conditions are sufficient to create two new species, while in the second the mating and genetic conditions must be synchronized in order to control the velocity of genetic drift. http://precedings.nature.com/documents/798/version/1 oai:nature.com:10101/npre.2007.798.1 http://hdl.handle.net/10101/npre.2007.798.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.800.1 2007-08-23T11:20:55Z genetics evolutionary-biology

Precise Similarity of Many Human Proteins to Proteins of Prokarya 2007-08-22T22:00:15Z Roy Britten Genetics & Genomics Evolutionary Biology 	 Proteins originated in early forms of life and have long survived, because they have always been required. Some recognizably similar proteins are found in all sequence comparisons between species, no matter how distant, including prokaryotes and eukaryotes. Reported here are observations on the relationships of human proteins to the proteins of 458 prokaryotes for which protein libraries are available. Each of these libraries includes a protein that matches a human protein with a BLAST score of 573 or more, indicating excellent conservation of certain amino acid sequences. A majority of these proteins also match a yeast protein and other eukaryote proteins with comparable accuracy, indicating that protein conservation is responsible in most cases rather than the horizontal transfer (HGT) between eukaryotes and prokaryotes. Rare examples of HGT are apparently also seen.
	Very many significant matches are seen as the criterion is opened, including 20,596 human proteins that match at least one prokaryote protein with expectation of 10-3 or less. Individual prokaryote proteins accurately match parts of many modern human proteins that have a wide range of functions showing directly that many proteins of different functions have evolved from an ancestral protein by duplication, rearrangement and divergence of function. The implication is that most or all modern proteins derive from the proteins of the last common ancestor with prokaryotes through many such events. 
 http://precedings.nature.com/documents/800/version/1 oai:nature.com:10.1038/npre.2007.800.1 http://dx.doi.org/10.1038/npre.2007.800.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.805.1 2007-08-23T11:53:20Z cancer development genetics

Metastasis as a faulty recapitulation of ontogeny 2007-08-23T09:49:44Z Ulf R. Rapp Cancer Developmental Biology Genetics & Genomics RAF oncogenes are involved in a variety of phenotypic switch phenomena. If for example oncogenic RAF is expressed together with Myc in B lineage cells, a lineage switch to macrophages occurs at low frequency in vitro and in vivo. In addition, if RAF is expressed in type II alveolar epithelial cells slow growing lung adenomas are formed and a switch from columnar to cuboidal cells is detected in these mice upon p53 deletion. A similar switch is also seen, if ectopic Myc is present in our lung tumor mouse model. Moreover, in the liver of these mice with both oncogenes metastases are found. If E-cadherin function is impaired in our RAF-dependent lung tumor model, a switch from adenoma to adenocarcinoma occurs and genes characteristic for the early endodermal lineage are expressed. Based on these data I propose a novel model of metastasis and describe its implications. The hallmark of the model is the induction of a state of plasticity in tumor cells, which allows the reversal of differentiation to an earlier point in their ontogenic history. http://precedings.nature.com/documents/805/version/1 oai:nature.com:10.1038/npre.2007.805.1 http://dx.doi.org/10.1038/npre.2007.805.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.808.1 2007-08-23T11:18:37Z ecology

The locomotion pattern of Baurusuchus salgadoensis Carvalho, Nobre & Campos, 2005 and the distribution of Baurusuchidae in Gondwanaland 2007-08-23T13:33:42Z Felipe M. Vasconcellos Thiago S. Marinho Ismar S. Carvalho Ecology Baurusuchus salgadoensis Carvalho, Nobre & Campos, 2005 is a ziphodont mesoeucrocodylian closely related to the Sebecosuchia. Cranial features indicate that this species had terrestrial predatory habits. The postcranial skeleton of B. salgadoensis show distinctive characteristics when compared to extant Crocodylomorpha. The dorsal vertebrae are close articulated with short and craniocaudally expanded neural spines, specially the posterior ones. The sacral vertebrae are robust and have the lateral processes highly fused to the ilium. The anterior caudal vertebrae are robust as the sacral ones but their neural spines are more stout, anteriorlly expanded and higher. The close articulation of the dorsal vertebrae may indicate a less flexible dorsal spine, ideal to limb-driven methods of locomotion. The high and expanded neural spines of the posterior dorsal and sacral vertebrae are associated to muscle attachment from the osteoderms and the pelvic musculature, all used in the limb-driven locomotion. The appendicular bones of B. salgadoensis are long and stout. They show a straight aspect of their diaphysis and very well- developed epiphysis. The femur is long when compared to extant crocodilians, showing a straight aspect in lateral view and a slight sigmoid aspect in frontal view. There is a small axial torsion at its proximal end. The fourth trochanter is pronouced and posteriorlly oriented. The proximal end possess a mesial projection that articulates itself to the illium, similar to those of Protosuchia and thecodont archosaurs as the Rauisuchia. The illium of B. salgadoensis present a lateral and posteriorlly expanded postaccetabular crest, similar to those observed in Rauisuchia and Protosuchia, referred as overhanging ilium. This pattern of articulation is observed in the rauisuchian thecodonts and interpreted as a characteristic trait of those able erect-posture and limb-driven predators of Triassic environments. B. salgadoensis exoskeleton has only two dorsal osteoderm rows that run from the neck to the tip of the tail. Most of the osteoderms are wider than longer, with a round lateral portion that does not articulate to any flank osteoderm. The only morphological difference appears at the caudalmost portion of the tail, where the osteoderms are craniocaudally elongated. The medial portion has little variation along the scutes rows and may bear medial lamellar dorsoventral structures of articulation to the adjacent bony plate. The anterior articular facet is discreet and the osteoderms are not as imbricated as occur in other crocodyliforms and even may not be imbricated at all. The pelvic region osteoderms have the tallest keel of the row that runs from the anterior articular facet to posteriosmost portion of the osteoderm. B. salgadoensis has a light exoskeleton and then is less encumbranced by it. Therefore, becaming more agile. The imbrication of dorsal armor assists the limb-driven locomotion of many crocodyliform by reducing the flexibility of the dorsal spine during the high-walk (erect stance). Therefore the long and stout limb bones, overhanging crest of the illium and the light weighted armor, also allowed to B. salgadoensis to have the limb-driven locomotion without this pattern of osteoderms. These anatomical data may indicate how the Baurusuchidae had a wide distribution in Gondwanaland as they were able to move across large distances. http://precedings.nature.com/documents/808/version/1 oai:nature.com:10.1038/npre.2007.808.1 http://dx.doi.org/10.1038/npre.2007.808.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.819.1 2007-08-24T10:01:17Z genetics plant-biology

CARE1, a TY3-gypsy long terminal repeat retrotransposon in the food legume chickpea (Cicer arietinum L) 2007-08-24T11:20:19Z Manoj D. R. Rajput Kailash C. Upadhyaya Genetics & Genomics Plant Biology We report a novel Ty3-gypsy long terminal repeat retrotransposon CARE1 (_Cicer arietinum_ retro-element 1) in chickpea. This 5920-bp AT-rich (63%) element carries 723-bp 5' and 897-bp 3' LTRs respectively flanking an internal region of 4300-bp. The LTRs of CARE1 show 93.9% nucleotide identity to each other and have 4-bp (ACTA) terminal inverted repeats. A 17-bp potential tRNAmet primer binding site downstream to 5' LTR and a 13-bp polypurine tract upstream to 3' LTR have been identified. The order of domains (Gag-proteinase-reverse transcriptase-RNaseH-integrase) in the deduced amino acid sequence and phylogenetic tree constructed using reverse transcriptase sequences places CARE1 in the gypsy group of retrotransposons. Homologues of a number of _cis_-elements including CCAAT, TATA and GT-1 have been detected in the regulatory region or the 5' LTR of CARE1. Transgenic tobacco plants containing 5' LTR:GUS construct show that its 5'-LTR is inactive in a heterologous system under normal as well as tissue culture conditions. Genomic Southern blot experiments using 5’LTR of the element as a probe show that CARE1 or its related elements are present in the genomes of various chickpea accessions from various geographic regions. http://precedings.nature.com/documents/819/version/1 oai:nature.com:10101/npre.2007.819.1 http://hdl.handle.net/10101/npre.2007.819.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.826.1 2007-08-27T09:46:57Z biotechnology chemistry ecology molecular-cell-biology

Hierarchical coexistence of universality and diversity controls robustness and multi-functionality in intermediate filament protein networks 2007-08-25T20:14:17Z Theodor Ackbarow Markus J. Buehler Biotechnology Chemistry Ecology Molecular Cell Biology Proteins constitute the elementary building blocks of a vast variety of biological materials such as cellular protein networks, spider silk or bone, where they create extremely robust, multi-functional materials by self-organization of structures over many length- and time scales, from nano to macro. Some of the structural features are commonly found in a many different tissues, that is, they are highly conserved. Examples of such universal building blocks include alpha-helices, beta-sheets or tropocollagen molecules. In contrast, other features are highly specific to tissue types, such as particular filament assemblies, beta-sheet nanocrystals in spider silk or tendon fascicles. These examples illustrate that the coexistence of universality and diversity – in the following referred to as the universality-diversity paradigm (UDP) – is an overarching feature in protein materials. This paradigm is a paradox: How can a structure be universal and diverse at the same time? In protein materials, the coexistence of universality and diversity is enabled by utilizing hierarchies, which serve as an additional dimension beyond the 3D or 4D physical space. This may be crucial to understand how their structure and properties are linked, and how these materials are capable of combining seemingly disparate properties such as strength and robustness. Here we illustrate how the UDP enables to unify universal building blocks and highly diversified patterns through formation of hierarchical structures that lead to multi-functional, robust yet highly adapted structures. We illustrate these concepts in an analysis of three types of intermediate filament proteins, including vimentin, lamin and keratin. http://precedings.nature.com/documents/826/version/1 oai:nature.com:10101/npre.2007.826.1 http://hdl.handle.net/10101/npre.2007.826.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.846.1 2007-08-28T09:13:44Z cancer development immunology

Pregnancy Obstructs Involution Stage II of the Mammary Gland in Cows: General Biological Implications 2007-08-28T09:30:13Z Nissim Silanikove Gabriel Leitner Ana-Maria Anug Uzi Merin Cancer Developmental Biology Immunology *Background*
Repeated research findings over the last 4 decades show that involution of mammary glands in dairy cows did not regress to same extend as that noticed in other mammalian species.

*Methodology/Principal Findings*
We took an advantage of a rare event in the normal modern dairy farming: A cow that was false-positively identified as being pregnant was "dried up" (i.e., induced into involution) conventionally about 60 before her expected parturition. This cow was culled, and samples of her mammary gland tissue were examined for gross histology. In this study we demonstrate for the first time that modern dairy cow may undergo extensive obliteration of the lobular-alveolar structure, as expected in involution stage II. 

*Conclusions/Significance*
We conclude that lack of histological evidence for the appearance of involution stage II in the vast majority of modern cow's population is related to the peculiar modern dairy husbandry, in which dairy cows are induced into involution still pregnant. Because retardation of involution stage II in pregnant mammals is most likely a general physiological phenomena, it might occurs in other mammals, particularly in lactating humans. Thus, based on basic comparative physiology considerations, we suggest that concurrent lactation and pregnancy should be considered as an independent risk factor for breast cancer. http://precedings.nature.com/documents/846/version/1 oai:nature.com:10101/npre.2007.846.1 http://hdl.handle.net/10101/npre.2007.846.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.858.1 2007-08-30T14:51:51Z molecular-cell-biology pharmacology bioinformatics

Analysis of circadian pattern reveals tissue-specific alternative transcription in leptin signaling pathway 2007-08-29T18:50:01Z Andrey Ptitsyn Jeffrey Gimble Molecular Cell Biology Pharmacology Bioinformatics *Background*
It has been previously reported that most mammalian genes display a circadian oscillation in their baseline expression. Consequently, the phase and amplitude of each component of a signal transduction cascade has downstream consequences. 

*Results*
We report our analysis of alternative transcripts in the leptin signaling pathway which is responsible for the systemic regulation of macronutrient storage and energy balance. We focused on the circadian expression pattern of a critical component of the leptin signaling system, suppressor of cytokine signaling 3 (SOCS3). On an Affymetrix GeneChip 430A2 microarray, this gene is represented by three probe sets targeting different regions within the 3’ end of the last exon. We demonstrate that in murine brown adipose tissue two downstream 3’ probe sets experience circadian baseline oscillation in counter-phase to the upstream probe set. Such differences in expression patterns are a telltale sign of alternative splicing within the last exon of SOCS3. In contrast, all three probe sets oscillated in a common phase in murine liver and white adipose tissue. This suggests that the regulation of SOCS3 expression in brown fat is tissue specific. Another component of the signaling pathway, Janus kinase (JAK), is directly regulated by SOCS and has alternative transcript probe sets oscillating in counter-phase in a white adipose tissue specific manner.
 
*Conclusion*
We hypothesize that differential oscillation of alternative transcripts may provide a mechanism to maintain steady levels of expression in spite of circadian baseline variation. http://precedings.nature.com/documents/858/version/1 oai:nature.com:10101/npre.2007.858.1 http://hdl.handle.net/10101/npre.2007.858.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.864.1 2007-08-30T11:32:01Z immunology microbiology molecular-cell-biology

Novel protein antigen (JHP940) from the genomic plasticity region of Helicobacter pylori induces TNF-alpha and Interleukin- 8 secretion by human macrophages 2007-08-30T14:28:42Z Niyaz Ahmed Ayesha Alvi Mohammed Rizwan Immunology Microbiology Molecular Cell Biology Plasticity region of the H. pylori genome comprises strain specific gene loci. We performed genotyping and functional biology of one such locus (jhp940) that was previously found to be functionally unknown but present in gastric cancer associated strains from many different countries. We found its geographic prevalence to be independent of cagA presence and disease status. Cloning, expression and purification of the JHP940 revealed a novel, ~36kDa protein in biologically active form. The same induced strong and significant levels of TNF-alpha and Interleukin-8 in human macrophages. Induction of these cytokines by JHP940 points to its putative role in chronic gastric inflammation and various other outcomes of H. pylori infection including gastric cancer. http://precedings.nature.com/documents/864/version/1 oai:nature.com:10.1038/npre.2007.864.1 http://dx.doi.org/10.1038/npre.2007.864.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.846.2 2007-09-03T12:04:14Z cancer development immunology

Pregnancy Obstructs Involution Stage II of the Mammary Gland in Cows: General Biological Implications 2007-09-03T11:42:34Z Gabriel Leitner Ana-Maria Anug Uzi Merin Nissim Silanikove Cancer Developmental Biology Immunology *Background*
Repeated research findings over the last 4 decades show that involution of mammary glands in dairy cows did not regress to same extend as that noticed in other mammalian species.

*Methodology/Principal Findings*
We took an advantage of a rare event in the normal modern dairy farming: A cow that was false-positively identified as being pregnant was "dried up" (i.e., induced into involution) conventionally about 60 before her expected parturition. This cow was culled, and samples of her mammary gland tissue were examined for gross histology. In this study we demonstrate for the first time that modern dairy cow may undergo extensive obliteration of the lobular-alveolar structure, as expected in involution stage II. 

*Conclusions/Significance*
We conclude that lack of histological evidence for the appearance of involution stage II in the vast majority of modern cow's population is related to the peculiar modern dairy husbandry, in which dairy cows are induced into involution still pregnant. Because retardation of involution stage II in pregnant mammals is most likely a general physiological phenomena, it might occurs in other mammals, particularly in lactating humans. Thus, based on basic comparative physiology considerations, we suggest that concurrent lactation and pregnancy should be considered as an independent risk factor for breast cancer. http://precedings.nature.com/documents/846/version/2 oai:nature.com:10101/npre.2007.846.2 http://hdl.handle.net/10101/npre.2007.846.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.905.1 2007-09-04T12:04:55Z genetics neuroscience

Mushroom-bodies mediate hierarchical interactions between fact- and skill-learning in _Drosophila_ 2007-09-04T09:03:05Z Björn Brembs Wolfgang Plendl Genetics & Genomics Neuroscience Different brain circuits mediate the acquisition of skills and habits (via operant/instrumental learning) and the acquisition of facts (via classical/Pavlovian learning). Realistic learning situations always comprise interactions of skill- and fact-learning components (composite learning). So far, these interactions have escaped thorough scrutiny. Fixed flying _Drosophila melanogaster_ at the torque meter provide one of the very few systems where the relationship of operant and classical predictors in composite learning can be studied with sufficient rigor. Experiments with wildtype, mutant and transgenic flies show that there is an interaction between predictive stimuli (classical component) and goal-directed actions (operant component) which makes composite conditioning more effective than the operant and classical components alone. _Rutabaga_ (_rut_) mutants are impaired in learning about the (classical) stimuli, but show improved (operant) behavior learning. This is the first evidence that operant and classical conditioning differ not only at the circuit, but also at the molecular level. The interaction between operant and classical components is reciprocal and hierarchical, such that an impaired classical component (in _rut_ flies) suppresses retrieval and an intact classical component suppresses acquisition of the operant component. Experiments with transgenic flies demonstrate that this suppression of operant acquisition is mediated by the mushroom-bodies and serves to ensure that the classical memories can be generalized for access by other behaviors. Extended training can overcome this suppression and transforms goal-directed actions into habitual responses. In conclusion, composite conditioning consists of two components with reciprocal, hierarchical interactions. Acquisition of the _rut_-dependent classical component suppresses acquisition of the _rut_-independent operant component via the mushroom-bodies. The operant component facilitates acquisition of the classical component via unknown, non-mushroom-body pathways. This interaction leads to efficient learning, enables generalization and prevents premature habit-formation. Habit formation after extended training reveals the gate-keeping role of the mushroom-bodies, allowing only well-rehearsed behaviors to consolidate into habits. http://precedings.nature.com/documents/905/version/1 oai:nature.com:10101/npre.2007.905.1 http://hdl.handle.net/10101/npre.2007.905.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.907.1 2007-09-04T10:59:03Z cancer ecology

Homologous self-organising scale-invariant properties characterise long range species spread and cancer invasion 2007-09-04T13:01:44Z Diana D. E. Marco Sergio S. A. Cannas Marcelo M. A. Montemurro Bo Hu Shiyuan Cheng Cancer Ecology The invariance of some system properties over a range of temporal and/or spatial scales is an attribute of many processes in nature1, often characterised by power law functions and fractal geometry2. In particular, there is growing consensus in that fat-tailed functions like the power law adequately describe long-distance dispersal (LDD) spread of organisms 3,4. Here we show that the spatial spread of individuals governed by a power law dispersal function is represented by a clear and unique signature, characterised by two properties: A fractal geometry of the boundaries of patches generated by dispersal with a fractal dimension D displaying universal features, and a disrupted patch size distribution characterised by two different power laws. Analysing patterns obtained by simulations and real patterns from species dispersal and cell spread in cancer invasion we show that both pattern properties are a direct result of LDD and localised dispersal and recruitment, reflecting population self-organisation. http://precedings.nature.com/documents/907/version/1 oai:nature.com:10101/npre.2007.907.1 http://hdl.handle.net/10101/npre.2007.907.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.917.1 2007-09-06T06:59:52Z bioinformatics

PAL: A Perl Script for Rapidly Identifying the Active Site of Large Protein Families 2007-09-05T03:50:58Z Andres A. Larrea Pablo A. Larrea Bioinformatics In the post-genomic era, with an ever-increasing amount of sequence information, it is critical to develop tools that assist in sifting through all the data to identify information amidst the noise. The two main steps in determining the functional sites in proteins are aligning a large set of homologous sequences and analyzing this large file to identify highly conserved residues. Although a number of tools exist for generating high quality alignments rapidly there are much fewer tools available for rapidly identifying conserved cores within that multiple sequence alignment. PAL, is a Perl script that rapidly identifies conserved residues present in a large alignment file. The strengths of PAL are: speed, flexibility and ease of use. http://precedings.nature.com/documents/917/version/1 oai:nature.com:10101/npre.2007.917.1 http://hdl.handle.net/10101/npre.2007.917.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.930.1 2007-09-06T15:21:03Z immunology microbiology molecular-cell-biology

Keratinocytes from human skin respond as typical immune cells after the stimulation with _Trichophyton rubrum_ 2007-09-06T13:32:14Z Alfonso E. Islas-Rodríguez Luz A. García-Madrid Immunology Microbiology Molecular Cell Biology _Trichophyton rubrum_ is the main agent causing dermatophytosis (1). Keratinocytes are
considered to be the first physical barrier of defense against pathogens (2). But not
only a physical barrier. They recognize antigens through Toll like receptors (TLR) (3).
The activation of this TLR, present on the surface of the keratinocytes, induce the
expression of different pro-inflammatory cytokines, co-stimulatory molecules and
antimicrobial peptides such as [beta]-defensins (4).
The main objective of this work is to determine if lipopolysaccharides of G – bacteria
(LPS), lipotheichoic acid from G+ bacteria (LTA), and conidias, isolated from _T. rubrum_
were able to activate the expression of TLR2 and TLR6 on the cell surface of a primary
culture of human keratinocytes through Flow cytometry. Furthermore we are looking for
the presence of [beta]-defensins 1 and 2, IL-1b and IL-8 in the supernatant, of the above
mentioned culture of cells, by Western blot.
From the flow cytometry data, the preliminary results showed an important dispersion
in terms of proliferation, increase in size and granularity of keratinocytes, from primary
cultures of skin from healthy donors, stimulated 6 hours with conidias of _T. rubrum_, and
LTA, but not when non stimulated, or stimulated with LPS (Fig 1).
When keratinocytes from primary cultures of skin from healthy donors were cultivated
48 hours, it was found dispersion in terms of proliferation, increase in size and
granularity when stimulated with conidias of _T. rubrum_, and LPS but not when non
stimulated, or stimulated with LTA (Fig 2).
The keratinocytes expressed increased levels of TLR2 and TLR6 when were
stimulated with LTA and less to _T. rubrum_, in the 6 hours cultures, but this last cells still
showed increased size (Fig 3).
The Keratinocytes expressed increased levels of TLR2 in the 48 hours cultures when
were stimulated with LPS and _T. rubrum_.(Fig 4)
Besides, [beta]-defensin-2 was detected in the supernatant of cultures of keratinocytes
stimulated with LPS (Fig 5).
It can preliminary be concluded that keratinocytes from primary cultures of human skin from healthy donors, are cells that respond as typical immune cells, after stimulation
with _T. rubrum_, LTA and LPS in different conditions, and that this mechanism may be
very important, for the protection of local environment. 

References
1.- Arenas R., Dermatofitosis en México. Rev Iberoam Micol 2002; 19: 63-67.
2.- Kupper T. and Fuhlbrigge R. Immune surveillance in the skin: mechanims and clinical consecuences.
Nat Rev Immunol 2004; 4: 211-222
3.- Kôllish G., Naderi B., Voelcker V., Wallich R., Behrendt H., Ring J., Bauer S., Jacob T., Mempel M. and
Olelrt M. Various members of the Toll-Like receptor family contribute to the innate immune response of
human epidermal keratinocytes. Immunology 2005; 114: 531-541.
4.- Akira, S. and Takeda K. 2004. Toll-like Receptor Signalling. Nature Reviews Immunology 4:499-511. http://precedings.nature.com/documents/930/version/1 oai:nature.com:10101/npre.2007.930.1 http://hdl.handle.net/10101/npre.2007.930.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.932.1 2007-09-06T13:37:53Z development ecology genetics microbiology

Telomeres in Evolution and Development from Biosemiotic Perspective 2007-09-06T17:01:14Z Guenther Witzany Developmental Biology Ecology Genetics & Genomics Microbiology Telomeres identify natural chromosome ends being different from broken DNA through differences in their "molecular syntax" (M.Eigen) which determines the functions of reverse transcriptase and its integrated RNA template, telomerase. Although telomeres play a crucial role in the linear chromosome organization of eukaryotic cells, their molecular syntax descended from an ancient retroviral competence. This is an indicator for the early retroviral colonization of large double stranded DNA viruses, which are putative ancestors of the eukaryotic nucleus.
This talk will demonstrate certain advantages of the biosemiotic approach towards our evolutionary understanding of telomeres: focus on the genetic/genomic structures as language-like text which follows combinatorial (syntactic), context-sensitive (pragmatic) and
content-specific (semantic) semiotic rules. Genetic/genomic organization from the biosemiotic perspective is not seen any longer as an object of randomly derived alterations (mutations) but as functional innovation coherent with the broad variety of natural genome editing competences of viruses.
 http://precedings.nature.com/documents/932/version/1 oai:nature.com:10.1038/npre.2007.932.1 http://dx.doi.org/10.1038/npre.2007.932.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.941.1 2007-09-07T10:28:21Z ecology plant-biology

Plant Functional Types and Plant Trait Measurements in the Eastern Ghats, South India 2007-09-07T11:35:58Z K. Anupama A. Stephen S. Aravajy G. Orukaimani Ecology Plant Biology Classifying terrestrial plant species on the basis of function rather than on taxonomy facilitates addressing ecological questions at the scale of ecosystems, landscapes or Biomes. The concept of plant functional types (PFTs) helps handle taxonomic diversity, as it groups together species that share common attributes with respect to, e.g. life-form, phenology and bioclimatic limits. For some time now, large international efforts promoted by the IGBP-GCTE programme are underway to measure for a large number of species a shortlist of significant plant traits that would underlie such functional plant classification systems. The idea here is to help address vegetation responses to and vegetation effects on environmental changes such as climate changes, but also others such as landuse or other disturbances. 
A PFT classification obviously helps in the use of pollen assemblages to infer past ecosystem changes, especially ecosystem response to climate change, as this is more directly linked to changes in functional rather than taxonomic diversity of plants over temporal and spatial gradients. 
We present a comprehensive list of pollen taxa from our database of surface samples from Eastern Ghats, South India to which PFTs are assigned based on our field observations of the Ecology and Biology of individuals as well as the description of the flora and vegetation of the Eastern Ghats in standard published floras. Finally, we also present trait measurements such as specific leaf area (SLA) and thickness for a shortlist of the taxa listed above.
 http://precedings.nature.com/documents/941/version/1 oai:nature.com:10.1038/npre.2007.941.1 http://dx.doi.org/10.1038/npre.2007.941.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.945.1 2007-09-07T16:54:21Z bioinformatics

Bridging the gap between social tagging and semantic annotation: E.D. the Entity Describer 2007-09-07T17:14:39Z Benjamin M. Good Edward A. Kawas Mark D. Wilkinson Bioinformatics Semantic annotation enables the development of efficient computational methods for analyzing and interacting with information, thus maximizing its value. With the already substantial and constantly expanding data generation capacity of the life sciences as well as the concomitant increase in the knowledge distributed in scientific articles, new ways to produce semantic annotations of this information are crucial. While automated techniques certainly facilitate the process, manual annotation remains the gold standard in most domains. In this manuscript, we describe a prototype mass-collaborative semantic annotation system that, by distributing the annotation workload across the broad community of biomedical researchers, may help to produce the volume of meaningful annotations needed by modern biomedical science. We present E.D., the Entity Describer, a mashup of the Connotea social tagging system, an index of semantic web-accessible controlled vocabularies, and a new public RDF database for storing social semantic annotations. http://precedings.nature.com/documents/945/version/1 oai:nature.com:10101/npre.2007.945.1 http://hdl.handle.net/10101/npre.2007.945.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.743.2 2007-09-12T11:04:26Z genetics evolutionary-biology

Aggregation of Single Nucleotide Polymorphisms in a Human H5N1 Clade 2.2 Hemagglutinin 2007-09-10T09:26:53Z Henry L. Niman Magdi D. Saad Jeffery Tjaden Kenneth C. Earhart Marshall R. Monteville Mona M. Aly Moustafa M. Mansour Nasr El-Sayed Ahmed E. Nayel Ahmed S. Abdelghani Hala M. Esmat Emad M. Labib Ehab A. Ayoub Abdelattar Arafa Gregory A. Raczniak Mensah Agyen-Frempong William K. Ampofo Bruce R. Boynton Genetics & Genomics Evolutionary Biology The rapid evolution of the H5N1 serotype of avian influenza has been explained by a mechanism involving the selection of single nucleotide polymorphisms generated by copy errors. The recent emergence of H5N1 Clade 2.2 in fifty countries, offered a unique opportunity to view the acquisition of new polymorphism in these evolving genomes. We analyzed the H5N1 hemagglutinin gene from a fatal human case from Nigeria in 2007. The newly emerged polymorphisms were present in diverse H5N1 isolates from the previous year. The aggregation of these polymorphisms from clade 2.2 sub-clades was not supported by recent random mutations, and was most easily explained by recombination between closely related sequences. http://precedings.nature.com/documents/743/version/2 oai:nature.com:10101/npre.2007.743.2 http://hdl.handle.net/10101/npre.2007.743.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.459.3 2007-09-12T10:27:59Z biotechnology chemistry ecology genetics immunology microbiology bioinformatics

Concurrent Acquisition of a Single Nucleotide Polymorphism in Diverse Influenza H5N1 Clade 2.2 Sub-clades 2007-09-10T12:42:43Z Henry L. Niman Magdi D. Saad Mona M. Aly Jeffery Tjaden Kenneth C. Earhart Marshall R. Monteville Moustafa M. Mansour Nasr El-Sayed Ahmed E. Nayel Ahmed S. Abdelghani Hala M. Esmat Emad M. Labib Ehab A. Ayoub Abdelattar Arafa Gregory A. Raczniak Mensah Agyen-Frempong William K. Ampofo Bruce R. Boynton Biotechnology Chemistry Ecology Genetics & Genomics Immunology Microbiology Bioinformatics Highly pathogenic Influenza A H5N1 was first identified in Guangdong Province in 1996, followed by human cases in Hong Kong in 1997. The number of confirmed human cases now exceeds 300, and the associated Case Fatality Rate exceeds 60%. The genetic diversity of the serotype continues to increase. Four distinct clades or sub-clades have been linked to human cases. The gradual genetic changes identified in the sub-clades have been attributed to copy errors by viral encoded polymerases that lack an editing function, thereby resulting in antigenic drift. We report here the concurrent acquisition of the same polymorphism by multiple, genetically distinct, clade 2.2 sub-clades in Egypt, Russia, and Ghana. These changes are not easily explained by the current theory of “random mutation” through copy error, and are more easily explained by recombination with a common source. This conclusion is supported by additional polymorphisms shared by clade 2.2 isolates in Egypt and Germany. http://precedings.nature.com/documents/459/version/3 oai:nature.com:10101/npre.2007.459.3 http://hdl.handle.net/10101/npre.2007.459.3 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.977.1 2007-09-12T13:23:55Z earth-and-environment

Remote estimation of carbon dioxide uptake of terrestrial ecosystems 2007-09-12T10:20:20Z Martin F. Garbulsky Earth & Environment The estimation of the carbon balance in ecosystems, regions, and the biosphere is currently one of the main concerns in the study of the ecology of global change. Current remote sensing methodologies for estimating gross primary productivity are not satisfactory because they rely too heavily on (i) the availability of climatic data, (ii) the definition of land-use cover, and (iii) the assumptions of the effects of these two factors on the radiation-use efficiency of vegetation (RUE). A new methodology is urgently needed that will actually assess RUE and overcome the problems associated with the capture of fluctuations in carbon absorption in space and over time. Remote sensing techniques such as the widely used reflectance vegetation indices (e.g., NDVI, EVI) allow green plant biomass and therefore plant photosynthetic capacity to be assessed. Nevertheless, detecting how much of this capacity is actually realized is a much more challenging goal. The Photochemical Reflectance Index (PRI) derived from freely available satellite information (MODIS sensor) presented an exponential relationship with the RUE. Thus, we show that it is possible to estimate RUE in real time and therefore actual carbon uptake at ecosystem, regional, and biosphere levels using the PRI. This conceptual and technological advancement avoids the need to rely on either the sometimes unreliable maximum RUE for each ecosystem, hard-to-obtain climate data, or on imprecise land-use/land-cover data. http://precedings.nature.com/documents/977/version/1 oai:nature.com:10101/npre.2007.977.1 http://hdl.handle.net/10101/npre.2007.977.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.980.1 2007-09-17T12:48:48Z bioinformatics

The Normal Fetal Heart Rate Study: Analysis Plan 2007-09-12T11:57:40Z Martin Daumer Michael Scholz Anne-Laure Boulesteix Stephanie Pildner von Steinburg Sven Schiermeier Wolfgang Hatzmann K T M Schneider Bioinformatics Recording of fetal heart rate via CTG monitoring has been routinely performed as an important part of antenatal and subpartum care for several decades. The current guidelines of the FIGO (ref1) recommend a normal range of the fetal heart rate from 110 to 150 bpm. However, there is no agreement in the medical community whether this is the correct range (ref2). We aim to address this question by computerized analysis (ref 3) of a high quality database (HQDb, ref 4) of about one billion electronically registered fetal heart rate measurements from about 10,000 pregnancies in three medical centres over seven years. In the present paper, we lay out a detailed analysis plan for this evidence-based project in the vein of the validation policy of the Sylvia Lawry Centre for Multiple Sclerosis Research (ref 5) with a split of the database into an exploratory part and a part reserved for validation. We will perform the analysis and the validation after publication of this plan in order to reduce the probability of publishing false positive research findings (ref 6-7). http://precedings.nature.com/documents/980/version/1 oai:nature.com:10.1038/npre.2007.980.1 http://dx.doi.org/10.1038/npre.2007.980.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.988.1 2007-09-13T04:38:32Z neuroscience

Decrease of vanillin sucrose intake by victorious and defeated mice: development of anhedonia? 2007-09-13T06:02:59Z Natalia N. Kudryavtseva Natalia P. Bondar Irina L. Kovalenko Damira F. Avgustinovich Neuroscience Hedonic reactions to various rewards play a key role in various forms of motivated behavior. The influence of repeated experience of social victories or defeats in daily agonistic interactions between male mice on voluntary consumption of vanillin sucrose solution used as hedonic reinforcer was studied. Intake of vanillin sucrose solution was shown to decrease in the winners and losers exposed to social confrontations as compared with the controls. Three days of deprivation failed to restore the intake of vanillin sucrose solution to the control level in the losers and did so in the winners. The results obtained imply that similar reaction of animals to a hedonic non-drug reinforcer may have different motivational origin depending on positive or negative social experience. http://precedings.nature.com/documents/988/version/1 oai:nature.com:10101/npre.2007.988.1 http://hdl.handle.net/10101/npre.2007.988.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.595.2 2007-09-17T13:55:20Z earth-and-environment

Visualization of and Access to CloudSat Vertical Data through Google Earth 2007-09-13T16:37:41Z Aijun Chen Gregory Leptoukh Liping Di Denis Nadeau John Farley Christopher Lynnes Steven Kempler Earth & Environment Online tools, pioneered by the Google Earth (GE), are facilitating the way in which scientists and general public interact with geospatial data in real three dimensions. However, even in Google Earth, there is no method for depicting vertical geospatial data derived from remote sensing satellites as an orbit curtain seen from above. Here, an effective solution is proposed to automatically render the vertical atmospheric data on Google Earth. The data are first processed through the Giovanni system, then, processed to be 15-second vertical data images. A generalized COLLADA model is devised based on the 15-second vertical data profile. Using the designed COLLADA models and satellite orbit coordinates, a satellite orbit model is designed and implemented in KML format to render the vertical atmospheric data in spatial and temporal ranges vividly. The whole orbit model consists of repeated model slices. The model slices, each representing 15 seconds of vertical data, are placed on the CloudSat orbit based on the size, scale, and angle with the longitude line that are precisely and separately calculated on the fly for each slice according to the CloudSat orbit coordinates. The resulting vertical scientific data can be viewed transparently or opaquely on Google Earth. Not only is the research bridged the science and data with scientists and the general public in the most popular way, but simultaneous visualization and efficient exploration of the relationships among quantitative geospatial data, e.g. comparing the vertical data profiles with MODIS and AIRS precipitation data, becomes possible. http://precedings.nature.com/documents/595/version/2 oai:nature.com:10.1038/npre.2007.595.2 http://dx.doi.org/10.1038/npre.2007.595.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1001.1 2007-09-18T12:51:43Z earth-and-environment

Impact of sea surface height anomalies on cyclone track 2007-09-14T04:16:40Z M.M Ali Palash Sinha Sarika Jain U.C Mohanty Earth & Environment Predicting accurate cyclone tracks is crucial for disaster management practices. The unusual westward movement of the 6-11 May 2002 Arabian Sea cyclone has been investigated through community mesoscale National Centre for Atmospheric Research model by giving different sea surface temperatures (SST) in different experiments keeping all other conditions same. In one experiment, we converted sea surface height anomalies (SSHAs) to SST. Oceanic eddies and SSHAs, representing the subsurface thermal structure, played a prominent role in the unusual westward movement of this cyclone. This is the first time that the effect of eddies and SSHAs on cyclone track has been reported. http://precedings.nature.com/documents/1001/version/1 oai:nature.com:10.1038/npre.2007.1001.1 http://dx.doi.org/10.1038/npre.2007.1001.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.977.2 2007-09-18T11:27:37Z earth-and-environment

Remote estimation of carbon dioxide uptake of terrestrial ecosystems 2007-09-17T09:13:51Z Martin F. Garbulsky Josep Peñuelas Dario Papale Iolanda Filella Earth & Environment The estimation of the carbon balance in ecosystems, regions, and the biosphere is currently one of the main concerns in the study of the ecology of global change. Current remote sensing methodologies for estimating gross primary productivity are not satisfactory because they rely too heavily on (i) the availability of climatic data, (ii) the definition of land-use cover, and (iii) the assumptions of the effects of these two factors on the radiation-use efficiency of vegetation (RUE). A new methodology is urgently needed that will actually assess RUE and overcome the problems associated with the capture of fluctuations in carbon absorption in space and over time. Remote sensing techniques such as the widely used reflectance vegetation indices (e.g., NDVI, EVI) allow green plant biomass and therefore plant photosynthetic capacity to be assessed. Nevertheless, detecting how much of this capacity is actually realized is a much more challenging goal. The Photochemical Reflectance Index (PRI) derived from freely available satellite information (MODIS sensor) presented an exponential relationship with the RUE. Thus, we show that it is possible to estimate RUE in real time and therefore actual carbon uptake at ecosystem, regional, and biosphere levels using the PRI. This conceptual and technological advancement avoids the need to rely on either the sometimes unreliable maximum RUE for each ecosystem, hard-to-obtain climate data, or on imprecise land-use/land-cover data. http://precedings.nature.com/documents/977/version/2 oai:nature.com:10101/npre.2007.977.2 http://hdl.handle.net/10101/npre.2007.977.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1028.1 2007-09-18T11:42:40Z bioinformatics evolutionary-biology

Towards a Taxonomically Intelligent Phylogenetic Database 2007-09-18T09:01:43Z Roderic Page Bioinformatics Evolutionary Biology This note outlines some of the key intellectual obstacles that stand in the way of creating a usable phylogenetic database. These challenges include the need to accommodate multiple taxonomic names and classifications, and the need for tools to query trees in biologically meaningful ways. Until these problems are addressed, and a taxonomically intelligent phylogenetic database created, much of our phylogenetic knowledge will languish in the pages of journals. http://precedings.nature.com/documents/1028/version/1 oai:nature.com:10.1038/npre.2007.1028.1 http://dx.doi.org/10.1038/npre.2007.1028.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1029.1 2007-09-18T10:48:38Z bioinformatics evolutionary-biology

On The Dangers Of Aligning RNA Sequences Using “Conserved” Motifs 2007-09-18T09:05:03Z Roderic Page Bioinformatics Evolutionary Biology Aligning RNA sequences can be a challenging task. Automatic sequence alignment programs typically align sequences only with respect to primary sequence, and as a result may yield spurious alignments. Incorporating information on RNA secondary structure can improve the alignment, but this must usually be done by hand. One approach to aligning RNA sequences uses "conserved motifs", however relying on these motifs may lead to gross errors of alignment if, in fact, those motifs are not conserved. http://precedings.nature.com/documents/1029/version/1 oai:nature.com:10.1038/npre.2007.1029.1 http://dx.doi.org/10.1038/npre.2007.1029.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1030.1 2007-09-18T10:49:19Z bioinformatics evolutionary-biology

Treemap Versus BPA (Again): A Response to Dowling 2007-09-18T09:09:58Z Roderic Page Michael Charleston Bioinformatics Evolutionary Biology TreeMap is a computer program for analysing host-parasite cospeciation. We respond to Dowling’s (Cladistics, 18: 416-435) recent comparison of TreeMap and Brooks Parsimony Analysis (BPA) by showing that Dowling’s comparison suffers from several mistakes and flaws. We discuss the problems with both BPA and TreeMap, and show that BPA incorrectly counts the true number coevolutionary events more often than TreeMap 1. We also discuss the two main limitations of TreeMap 1 correctly identified by Dowling, namely its inability to handle widespread parasites, and its coarse optimality criterion (the number of cospeciation events). We suggest a simple fix for widespread parasites. The newly released TreeMap 2 uses a more sensitive optimality criterion than TreeMap 1, addressing Dowling’s second concern. http://precedings.nature.com/documents/1030/version/1 oai:nature.com:10.1038/npre.2007.1030.1 http://dx.doi.org/10.1038/npre.2007.1030.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1036.1 2007-09-19T17:07:01Z biotechnology genetics molecular-cell-biology pharmacology bioinformatics

DNA expression microarrays may be the wrong tool to identify biological pathways 2007-09-18T13:09:38Z Adrian Mondry Marie Loh Alessandro Giuliani Biotechnology Genetics & Genomics Molecular Cell Biology Pharmacology Bioinformatics DNA microarray expression signatures are expected to provide new insights into patho- physiological pathways. Numerous variant statistical methods have been described for each step of the signal analysis. We employed five similar statistical tests on the same data set at the level of gene selection. Inter-test agreement for the identification of biological pathways in BioCarta, KEGG and Reactome was calculated using Cohen’s k- score. The identification of specific biological pathways showed only moderate agreement (0.30 < k < 0.79) between the analysis methods used. Pathways identified by microarrays must be treated cautiously as they vary according to the statistical method used. http://precedings.nature.com/documents/1036/version/1 oai:nature.com:10.1038/npre.2007.1036.1 http://dx.doi.org/10.1038/npre.2007.1036.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1046.1 2007-09-19T08:09:39Z neuroscience bioinformatics

Workshop report: 1st INCF Workshop on Mouse and Rat Brain Digital Atlasing Systems 2007-09-19T09:29:18Z Jyl Boline Michael Hawrylycz Robert W. Williams Neuroscience Bioinformatics The goal of this workshop was to survey current activities and plans related to development of mouse and rat brain digital atlasing systems. The workshop discussed needs for and types of coordinated action that will ensure rapid progress, compatibility, and dissemination with use of novel technological approaches. The report summarizes the state-of-the-art in the field and provides recommendations for actions. http://precedings.nature.com/documents/1046/version/1 oai:nature.com:10.1038/npre.2007.1046.1 http://dx.doi.org/10.1038/npre.2007.1046.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1047.1 2007-09-19T09:25:18Z molecular-cell-biology bioinformatics

Modeling of ARS-interacting multifunctional proteins p18 and p38. 2007-09-19T10:15:06Z Viktor V. Deineko Molecular Cell Biology Bioinformatics ARS-interacting multifunctional proteins (auxiliary components) – are nonezymatic proteins, associated with aminoacyl-tRNA synthetases – enzymes that catalyse the joining of amino acids with their corresponding tRNAs. All these proteins are complexed into large macromolecular multisynthetase complex in eukaryotes. It includes nine different ARSs and three auxiliary components. Their spatial structures precisely defined by X-ray analysis are still not known. Nevertheless, it very useful to have this structure while making biochemical studies. Bioinformatical tools were used to create structural models of two auxiliary components of multisynthetase complex – p18 and p38. http://precedings.nature.com/documents/1047/version/1 oai:nature.com:10.1038/npre.2007.1047.1 http://dx.doi.org/10.1038/npre.2007.1047.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1056.1 2007-09-26T05:03:33Z biotechnology cancer genetics molecular-cell-biology pharmacology bioinformatics

Diagnostic robustness of DNA microarrays in the classification of acute leukemia 2007-09-20T15:34:38Z Marie Loh Adrian Mondry Biotechnology Cancer Genetics & Genomics Molecular Cell Biology Pharmacology Bioinformatics Countless statistical methods have been described for the analysis of DNA microarrays, and each yields distinct results. This raises the question whether DNA microarrays are robust diagnostic tools.

In order to address this issue, we compared five formally similar statistical tests for gene selection on a single data set derived from acute leukemia patients. Inter-test agreement of gene selection, of sample classification and with standard clinical diagnosis was calculated using Cohen's κ-score.

The inter-test agreement scores were 0.15 < κ < 0.68 for gene selection, and 0.60 < κ < 0.89 for sample classification. Comparison to the clinical diagnosis showed agreement scores of 0.58< κ < 0.88. 'Marginal imbalance' explains the low κ-scores at the level of gene selection. At the levels of sample classification and agreement with clinical diagnosis, κ-scores can be considered "substantial" to "excellent".

For diagnostic purposes, the inter-test agreement of DNA microarrays is equivalent to that of experienced clinicians, as reported in the literature. The technique can thus be considered a useful and robust addendum to the available diagnostic tools.
 http://precedings.nature.com/documents/1056/version/1 oai:nature.com:10.1038/npre.2007.1056.1 http://dx.doi.org/10.1038/npre.2007.1056.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1068.1 2007-09-21T12:10:21Z immunology microbiology molecular-cell-biology

Stomatin-like Protein 2 Links Mitochondria to T-Cell Receptor Signalosomes at the Immunological Synapse and Enhances T-Cell Activation 2007-09-21T15:21:24Z Mark G. Kirchhof Luan A. Chau Caitlin D. Lemke Santosh Vardhana Peter J. Darlington Maria E. Marquez Roy Taylor Kamilia Rizkalla Isaac Blaca Michael L. Dustin Joaquin Madrenas Immunology Microbiology Molecular Cell Biology T cell activation through the antigen receptor (TCR) requires sustained signalling from microclusters in the peripheral region of the immunological synapse (IS). The bioenergetics of such prolonged signaling have been linked to the redistribution of mitochondria to the IS. Here, we report that stomatin-like protein-2 (SLP-2) plays an important role in this process by bridging polarized mitochondria to these signaling TCR microclusters or signalosomes in the IS in a polymerized actin-dependent manner. In this way, SLP-2 helps to sustain TCR-dependent signalling and enhances T cell activation. http://precedings.nature.com/documents/1068/version/1 oai:nature.com:10101/npre.2007.1068.1 http://hdl.handle.net/10101/npre.2007.1068.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1071.1 2007-09-21T19:36:59Z earth-and-environment

Understanding and mapping water resources by multidimensional statistics and fuzzy logic: Missouri River basin case 2007-09-21T20:17:43Z Boris Shmagin Din Chen Earth & Environment Time series from 46 gauging station with drainage areas from 113 to 398 sq mi in the Upper Missouri River basin with mutual period of observation from 1963 to 1991 were used for analysis. Factor analysis of average annual flow revealed five patterns of river runoff within four distinct subregions of the territory (east, two carbonate karsts areas, uplands). This factor model reflected 62% variance of initial matrix. Each of four groups of watersheds obtained as a factor was presented by one gauging station with time series of annual and monthly discharges (I- 06218500, II- 06478690, III- 06412500, and IV- 06323000). Streams represented by patterns I, II and IV have increase of values and those represented by III have a decrease. The positive trend for pattern II is statistically significant. For four typical flow records, monthly average values were obtained from three to four seasons composed of different ensembles of months. The trends for seasonal components were analyzed for four typical watersheds and a significant increase was obtained for fall-winter season for type IV. Stream runoff is the most appropriate regional indicator for hydroclimatological processes. With multidimensional statistics this process can be considered as spatiotemporal structure of different scale of landscape properties and dynamics. Uncertainties of process originating stream runoff based on dynamic of regional meteorological system and diversity of local landscapes. Boundaries for domains with different annul and seasonal regimes of stream runoff were defined with factor loadings and fuzzy logic rules. With case of Missouri River basin presented that more complete decryption of real events in nature requires use probability and fuzzy logic together. http://precedings.nature.com/documents/1071/version/1 oai:nature.com:10.1038/npre.2007.1071.1 http://dx.doi.org/10.1038/npre.2007.1071.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1082.1 2007-09-24T04:58:06Z earth-and-environment

South Dakota Diversity of Temperature: Pictures from Statistical Analysis 2007-09-22T15:18:19Z Boris Shmagin Dennis Todey Earth & Environment The regional diversity of monthly temperature was analyzed based on long-term data obtained for South Dakota (SD) from the High Plains Regional Climate Center. Multidimensional statistical methods were used and the principal results presented as a sequence of 2- and 3-dimensional scatterplot pictures depicting the quantitative results. 
System hierarchical model of landscape was used for research tasks formulation. Initial matrixes for three research tasks were compiled for the state. The first set of initial matrices of time series {Xt*n}, where t = number of years and n = number of meteorological stations, contains two matrixes: X1(67*29) and X2(33*94). The second set -{Xt*m}, where t = number of years and m = number of months in a year: X3(113*12), X4(110*12), and X5(102*12). The third set - {Xn*m}, where n = number of meteorological stations and m = number of months in a year, contains two matrixes: X6(29*12) and X7(94*12). 
Statistical analysis allowed us to differentiate weather stations by temporal trends and spatial distribution for the time interval 1932-1998. The most variable stations (Brookings, Camp Crook, and Highmore) were determined; their seasonality was described (the most variable months and correlation among months during the year) and their seasonal regime determined. The average annual and monthly temperature distributions were presented for South Dakota based on 29 and 94 stations for the time intervals 1932-1998 and 1963-1995.
 http://precedings.nature.com/documents/1082/version/1 oai:nature.com:10101/npre.2007.1082.1 http://hdl.handle.net/10101/npre.2007.1082.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1094.1 2007-09-26T08:33:19Z ecology bioinformatics plant-biology

PlnTFDB: Plant Transcription Factor Database – Update 2007-09-24T11:25:35Z Diego Mauricio Riaño-Pachón Luiz Gustavo Guedes Correa Bernd Mueller-Roeber Ecology Bioinformatics Plant Biology PlnTFDB is a publicly available computational resource comprising putative complete sets of transcription factors from plants. The original database listed the putative complete sets of TFs from five different green plant (viridiplantae) species. Up to date, summer 2007, PlnTFDB have had more than one hundred thousand hits from more than one thousand different clients, showing the importance that this resource had acquired for the plant community. In this first major update, we extended the coverage of the database to additional completed viridiplantae genomes, i.e., the moss _Physcomitrella patens_ and the rice _Oryza sativa_ spp _indica_. The scope of PlnTFDB was broadened to encompass other eukaryote photosynthetic organisms, such as the rhodophyte algae _Galdieria sulphuraria_ and _Cyanidioschyzon merolae_, and the diatom _Thalassiosira pseudonana_. This will allow acquiring a better knowledge of plant evolution and on differentiation events. Moreover, the inclusion of large EST collections (i.e., _Hordeum vulgare_) have further extended the range of this resource to species whose genome are not yet sequenced but that have, nevertheless, highthroughput EST sequencing projects ongoing. http://precedings.nature.com/documents/1094/version/1 oai:nature.com:10.1038/npre.2007.1094.1 http://dx.doi.org/10.1038/npre.2007.1094.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.945.2 2007-09-24T11:49:10Z bioinformatics

Bridging the gap between social tagging and semantic annotation: E.D. the Entity Describer 2007-09-24T15:13:05Z Benjamin M. Good Edward A. Kawas Mark D. Wilkinson Bioinformatics Semantic annotation enables the development of efficient computational methods for analyzing and interacting with information, thus maximizing its value. With the already substantial and constantly expanding data generation capacity of the life sciences as well as the concomitant increase in the knowledge distributed in scientific articles, new ways to produce semantic annotations of this information are crucial. While automated techniques certainly facilitate the process, manual annotation remains the gold standard in most domains. In this manuscript, we describe a prototype mass-collaborative semantic annotation system that, by distributing the annotation workload across the broad community of biomedical researchers, may help to produce the volume of meaningful annotations needed by modern biomedical science. We present E.D., the Entity Describer, a mashup of the Connotea social tagging system, an index of semantic web-accessible controlled vocabularies, and a new public RDF database for storing social semantic annotations. http://precedings.nature.com/documents/945/version/2 oai:nature.com:10101/npre.2007.945.2 http://hdl.handle.net/10101/npre.2007.945.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1130.1 2007-09-27T14:49:10Z biotechnology

Open Notebook Science: Perspectives from a newbie 2007-09-26T19:37:05Z Cameron Neylon Biotechnology My group is using an electronic lab notebook based on a Blog format that is being developed in collaboration with the group of Professor Jeremy Frey. Here I discuss how this led to the adoption of an open notebook science approach in my group as well as some of the consequences, both positive and negative, of adopting such an approach. http://precedings.nature.com/documents/1130/version/1 oai:nature.com:10.1038/npre.2007.1130.1 http://dx.doi.org/10.1038/npre.2007.1130.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1145.1 2007-09-27T11:47:29Z immunology molecular-cell-biology bioinformatics

The Immune Response in Patients with SARS: differential gene expression profiling. 2007-09-27T14:19:42Z Peter Natesan Pushparaj Jayapal J. Manikandan Alirio Jose A. J. Melendez Immunology Molecular Cell Biology Bioinformatics Severe acute respiratory syndrome (SARS) emerged in 2003, as a new epidemic form of life-threatening infection. As of 26th September 2003, there were 8422 cases of SARS from 29 countries with 908 deaths (WHO). However, the pathogenesis of SARS is poorly understood. To understand the host response to this pathogen, we profiled the gene expression patterns of peripheral blood mononuclear cells (PBMC) from SARS patients compared to healthy controls using one of the latest techniques, high density oligonucleotide expression probe array (HG-Focus array, Gene Chip, Affymetrix, Santa Clara, CA). High-density oligonucleotide microarray is a promising approach for high throughput analysis. It has been extensively
used in many areas of biomedical research for different purposes. Thus we could compare the expression levels of thousands of genes which are differentially expressed in SARS patients over healthy controls. Among the most prominent findings, we observed 2 to 200-fold increased expression of transcripts of various genes. This enabled us to classify and cluster genes by functional families as well as to understand known genes in signaling
pathways. http://precedings.nature.com/documents/1145/version/1 oai:nature.com:10.1038/npre.2007.1145.1 http://dx.doi.org/10.1038/npre.2007.1145.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1147.1 2007-09-27T11:55:30Z immunology molecular-cell-biology pharmacology

siRNA knockdown of SPHK1 in vivo protects mice from systemic, type-I Allergy. 2007-09-27T14:31:06Z Jayapal J. Manikandan Peter Natesan P. N. Pushparaj Alirio Jose A. J. Melendez Immunology Molecular Cell Biology Pharmacology Systemic anaphylaxis is considered to be a typical immediate hypersensitivity response, determined by the activation of immune cells,
via antigen-induced aggregation of IgE-sensitized FcεRI cells. Perhaps most the important cells, in the immediate hypersensitivity responses, are mast cells. We have previously shown that SPHK1 plays a key role in the intracellular signaling pathways triggered by FceRI aggregation on human
mast cells. More recently, we performed a genome-wide gene expression profiling of human mast cells, sensitized with IgE alone, or stimulated by FcεRI aggregation. We found that sphingosine kinase 1 (SPHK1) was one
of genes activated at the earlier stages of mast cell activation, including during sensitization. Moreover, SPHK1 has been shown, by us and others, to be a key player in the intracellular signaling pathways triggered by
several immune-receptors, including fMLP, C5a, and Fcg- and Fcereceptors. Here we have investigated the in vivo role of SPHK1 in allergy, using a specific siRNA to knockdown SPHK1 in vivo. Our results support a role for
SPHK1 in the inflammatory responses that share clinical, immunological, and histological features of type I hypersensitivity. Thus, mice pretreated with the siRNA for SPHK1 were protected from the IgE mediated allergic
reactions including: temperature changes, histamine release, cytokine production, cell-adhesion molecule expression, and immune cell infiltration into the lungs. http://precedings.nature.com/documents/1147/version/1 oai:nature.com:10.1038/npre.2007.1147.1 http://dx.doi.org/10.1038/npre.2007.1147.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1148.1 2007-09-28T11:15:59Z immunology molecular-cell-biology pharmacology bioinformatics

Differential Gene Expression of Human Mast cell Activation Reveals Gene profiles of Innate and Adaptive Immunity. 2007-09-27T14:37:27Z Jayapal J. Manikandan Reghunathan Renji Peter Natesan Pushparaj Alirio Jose Melendez Immunology Molecular Cell Biology Pharmacology Bioinformatics High-density oligonucleotide microarray is a promising approach for high throughput analysis. It has been extensively used in many areas of biomedical research. Immunoglobulin E (IgE) mediated allergic response (type-1 hypersensitivity) is one of the most powerful reactions of the immune system. Tissue Mast Cells (MCs) and circulating basophils are the major effector cells in these reactions. By dissecting the regulatory circuitry of mast cells by analyzing the genome wide effects of antigen stimulation triggered by FcεRI, offers a potential for finding novel genes as ‘targets’ for therapeutic intervention. In this work, we tried to study the gene expression pattern in IgE sensitized and FcεRI cross linked cord blood derived MCs using one of the latest techniques, high density oligonucleotide expression probe array (HG-Focus array, Gene Chip, Affymetrix, Santa Clara, CA). Microarray hybridization of RNA from cord blood derived MCs revealed coordinated changes in gene expression in response to IgE stimulation and receptor cross linking at different time points. Among the most prominent findings, we observed 2 to 32-fold increased expression of different transcripts. Real-time PCR confirmed reliability of microarray data. This enabled us to classify and cluster genes by functional families as well as to understand known genes in signaling pathways. These results defined a list of primary candidates for finding novel genes as ‘targets’ for therapeutic intervention. http://precedings.nature.com/documents/1148/version/1 oai:nature.com:10.1038/npre.2007.1148.1 http://dx.doi.org/10.1038/npre.2007.1148.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1149.1 2007-09-28T11:22:43Z immunology molecular-cell-biology bioinformatics

Differences in the gene expression profile of human monocytic cells activated by high and low affinity Fc-gamma-receptors. 2007-09-27T14:42:47Z Jayapal J. Manikandan Renji Reghunathan Alirio Jose Melendez Peter Natesan Pushparaj Immunology Molecular Cell Biology Bioinformatics Receptors for the constant (Fc) region of immunoglobulin G, play an important role in linking the humoral and cellular arms of immune response. Three different classes of receptors have been defined, FcγRI (CD64), FcγRII (CD 32), and FcγRIII (CD16). We have previously shown that in a human monocyte model (IFNγ-primed U937 cells), FcγRI and FcγRII stimulation trigger two very distinct intracellular signalling pathways. Here we show for the first time, the use of oligonucleotide microarrays to investigate the overall gene-expression profile of human monocytes triggered with FcγRI or FcγRII. Our data indicate that several interesting genes are differentially expressed in response to the different receptors, pointing out to a complete different genetic response of human monocytes regulated by the different signal transduction cascade triggered by FcγRI or FcγRIIa. Thus, providing new insights into the different mechanisms utilized by the different IgG receptors to effect their functions. http://precedings.nature.com/documents/1149/version/1 oai:nature.com:10.1038/npre.2007.1149.1 http://dx.doi.org/10.1038/npre.2007.1149.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1150.1 2007-09-28T11:34:30Z immunology molecular-cell-biology pharmacology bioinformatics

Genome activity profiling of monomeric-IgE and Fc-epsilon-RI-aggregation on human mast cells reveals a complex network of genes involved in inflammatory responses. 2007-09-27T14:50:38Z Jayapal J. Manikandan Alirio Jose P. N. Melendez Peter Natesan A. J. Pushparaj Immunology Molecular Cell Biology Pharmacology Bioinformatics Mast cell activation, mediates type-1 allergic responses, one of the most powerful reactions of the immune system. However, mast cells activation is becoming increasingly linked to inflammatory, autoimmunity, and to adaptive immunity by regulating T-cell activation.
Here we analyzed the gene expression pattern in IgE-sensitized and FcεRI aggregation on human mast cells. Our data revealed coordinated changes in gene expression. We observed increased expression of gene-transcripts involved in allergic, innate and adaptive
immune responses. Among the most prominent findings is the increased expression of transcripts encoding for MIP3a, SPARCL1, AREG, IL18, CCL1, TNFRSF9, IL1b, CX3CR1, PTGER3, MIF, MMP12, ADORA3, IL8RB, and other genes involved in innate and cellmediated
immunity. These results represent a substantial advance in our understanding of the genome-wide effects triggered by “passive sensitization” or active stimulation of human mast cells, and how this relate to mast cells involvement not only in allergic
responses but also in innate and adaptive immunity. http://precedings.nature.com/documents/1150/version/1 oai:nature.com:10.1038/npre.2007.1150.1 http://dx.doi.org/10.1038/npre.2007.1150.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1176.1 2007-09-28T09:15:45Z pharmacology plant-biology

Current status of herbal and their future perspectives 2007-09-28T08:14:31Z Ramar Perumal R. Samy Ponnampalam Gopalakrishnakone Pharmacology Plant Biology Traditional medicine is the synthesis of therapeutic experience of generations of practicing physicians of indigenous systems of medicine. Throughout the history of mankind, many infectious diseases have been treated with herbals. The traditional medicine is increasingly solicited through the tradipractitioners and herbalists in the treatment of infectious diseases. Among the remedies used, plant drugs constitute an important part. A number of scientific investigations have highlighted the importance and the contribution of many plant families i.e. Asteraceae, Liliaceae, Apocynaceae, Solanaceae, Caesalpinaceae, Rutaceae, Piperaceae, Sapotaceae used as medicinal plants. Medicinal plants play a vital role for the development of new drugs (export and import diverse parts or bioactive compounds in the current market). The bioactive extract should be standardized on the basis of active compound. The bioactive extract should undergo limited safety studies. http://precedings.nature.com/documents/1176/version/1 oai:nature.com:10101/npre.2007.1176.1 http://hdl.handle.net/10101/npre.2007.1176.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1182.1 2007-09-28T10:49:46Z biotechnology microbiology

Transparent Exopolymer Particles (TEP): an overlooked factor in the process of biofilm formation in aquatic environments 2007-09-28T11:05:11Z Tom Berman Uta Passow Biotechnology Microbiology We hypothesize that transparent exopolymer particles (TEP), present in high concentrations in most sea and freshwaters, are critical agents for biofilm initiation and development in many natural and anthropogenic aquatic environments. These gel-like particles appear in many forms; amorphous blobs, clouds, sheets, filaments or clumps ranging in size from ~2 to ~200 µm. TEP are mostly polysaccharide, negatively charged, very sticky and are frequently colonized by bacteria. TEP may be considered a "planktonic" subgroup of exopolymeric substances (EPS), widely studied in biofilm research. Recognition of TEP involvement in biofilm formation has important implications for a comprehensive understanding of the complexities of this process in aquatic environments and may also contribute to the considerable efforts being made in the global water industry to mitigate the harmful effects of biofouling in water treatment and desalination plants. http://precedings.nature.com/documents/1182/version/1 oai:nature.com:10.1038/npre.2007.1182.1 http://dx.doi.org/10.1038/npre.2007.1182.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1188.1 2007-09-28T12:09:16Z ecology

Through Birds' Eyes: What does vision tell us about foraging in cormorants? 2007-09-28T15:43:47Z Graham Martin Ecology Great Cormorants _Phalacrocorax carbo_ are regarded as visually-guided, pursuit-dive foragers, so it would be expected that they have excellent vision much like aerial predators, such as hawks which detect and pursue prey from a distance. However, my research shows that underwater the visual acuity of Cormorants is surprisingly poor (in fact, similar or worse than unaided humans under water) and very inferior to that of aerial predatory birds. I suggest that Cormorants are able to detect typical prey items only at close range and conclude that cormorants are not the aquatic equivalent of hawks. It seems that their efficient hunting involves the use of specialised foraging techniques which employ rapid neck extension to capture prey that cormorants flush from hiding places; much like the foraging techniques of herons. Cormorants seem to be hunting an “escaping blur”. Like herons, the eye movements and visual fields of cormorants allow visual scanning for escaping prey in a wide arc about the head. The ability of cormorants to see prey held in the mouth may help to aid its identification when it is brought to the surface before swallowing.
 http://precedings.nature.com/documents/1188/version/1 oai:nature.com:10.1038/npre.2007.1188.1 http://dx.doi.org/10.1038/npre.2007.1188.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1190.1 2007-09-30T20:17:49Z immunology pharmacology

Tumor necrosis factor and caspase in response to soluble or microparticle-incorporated drugs in Mycobacterium tuberculosis infection 2007-09-28T17:12:27Z Awadh Bihari Yadav Amit Misra Immunology Pharmacology We compared the effects of microparticles (MP) containig anti-tubercular drugs and those of the drugs themselves on the host macrophage (MΦ) response to infection with Mycobacterium tuberculosis H37Ra (Mtb). 
Mice infected intravenously with M. tb. were either administered rifampicin and isoniazid by oral gavage or through inhalation of biodegradable MP containing the two anti-tubercular drugs. Bronchoalveolar lavage (BAL) was perfomed to recover lung MΦ, which were cultured and the supernatant analysed for TNFα by ELISA. The murine MΦ cell line J774 or the human monocyte line THP-1 differentiated with phorbol myristate were infected in vitro and treated with MP or soluble drugs. The kinetics of secretion of TNFα were determined. Caspase-3 activity after infection and treatment was assesed using a substrate cleavage detection kit.
MP, but not soluble drugs, strongly induced TNFα in infected cells. Uninfected cells also responded to MP, although less strongly. Caspase-3 was observed to be upregulated
We conclude that MP treatment induces infected MΦ to upregulate the Th1 cytokine TNFα and Caspase-3, creating conditions for induction of apoptosis in these cells as a strategy to overcome infection.
 http://precedings.nature.com/documents/1190/version/1 oai:nature.com:10.1038/npre.2007.1190.1 http://dx.doi.org/10.1038/npre.2007.1190.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1191.1 2007-09-28T21:29:52Z immunology molecular-cell-biology

The Roles of Membrane Rafts in CD32A-Mediated Phagocytosis 2007-09-28T20:03:02Z Timothy P. Tolentino Periasamy Selvaraj Cheng Zhu Immunology Molecular Cell Biology Membrane rafts are highly dynamic heterogeneous sterol- and sphingolipid-rich micro-domains on cell surfaces. They are generally believed to provide residency for cell surface molecules (e.g., adhesion and signaling molecules) and scaffolding to facilitate the functions of these molecules such as membrane trafficking, receptor transport, cell signaling, and endocytosis.
The governing, or overall hypothesis, for this project is that membrane rafts provide residency for Fc[gamma]RIIA (CD32A) on K562 cells, and that by doing so they provide a platform from which Fc[gamma]RIIA initiate or carry out their functions, which include migration, signaling, phagocytic synapse formation, and internalization of IgG opsonized targets.
Using immuno-fluorescent laser scanning confocal microscopy and reflection interference microscopy (RIM), we studied the spatial and temporal distributions of membrane rafts and surface receptors, signaling molecules, and cell organelles during the formation of phagocytic contact areas. K562 cells, which naturally express CD32A, a cell surface receptor for the Fc portion of Immuno-globulin G(IgG), was chosen as a model for neutrophils. An opsonized target was modeled using a glass supported lipid bilayer reconstituted with IgG. CD32A was found to cluster and co-localize with membrane rafts. Placing the K562 cells on the lipid bilayer triggered a process of contact area formation that includes binding between receptors and ligands, their recruitment to the contact area, a concurrent membrane raft movement to and concentration in the contact area, and transport of CD32A, IgG, and membrane rafts to the Golgi complex. Characterization of these processes was performed using agents known to disrupt detergent resistant membranes (DRMs), dissolve actin microfilaments, and inhibit myosin motor activity, which abolished the CD32A clusters and prevented the contact area formation. 
The relevance to phagocytosis of contact area formation between K562 cells and lipid bilayers was demonstrated using micro-beads coated with a lipid bilayer reconstituted with IgG as the opsonized target instead of the glass supported planar lipid bilayer. Disruption of membrane rafts, salvation of the actin cytoskeleton, and inhibition of myosin II activity were found to inhibit phagocytosis.
These data suggest membrane rafts play several important roles in CD32A mediated phagocytosis including pre-clustering CD32A, transport of CD32A to the phagocytic cup, and transport of the opsonized target towards the Golgi complex. Here we have provided evidence that membrane rafts serve as platforms which are used to cluster CD32A and transport CD32A along the actin cytoskeleton to the site of phagocytic synapse formation thus allowing for the quick assembly of a phagocytic synapse.
 http://precedings.nature.com/documents/1191/version/1 oai:nature.com:10.1038/npre.2007.1191.1 http://dx.doi.org/10.1038/npre.2007.1191.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1195.1 2007-10-01T18:55:50Z neuroscience

Selective loss of GABAB receptors in orexin/hypocretin-producing neurons results in disrupted sleep/wakefulness architecture 2007-09-29T00:53:42Z Takeshi Sakurai Taizo Matsuki Hitomi Takahira Noriko Hirashima Thomas Kilduff Satoshi Kunita Satoru Takahashi Ken-ichi Yagami Bernard Bettler Masashi Yanagisawa Mika Nomiyama Neuroscience We generated mice with a selective loss of GABAB receptors in orexin neurons. Orexin neurons in these GABAB1<sup>-/-(orexin)</sup> mice showed reduced responsiveness to GABA<sub>A</sub> receptor agonists due to a compensatory increase in GABAA receptor-mediated inhibition. This increased GABA<sub>A</sub> receptor-mediated inhibition of orexin neurons is due to orexin-1 receptor-mediated activation of local GABAergic interneurons. Surprisingly, orexin neurons were also less responsive to glutamate, apparently because the augmented GABA<sub>A</sub> receptor-mediated inhibition increases the membrane conductance and shunts excitatory currents. These observations indicate that absence of GABA<sub>B</sub> receptors decreases the sensitivity of orexin neurons to both excitatory and inhibitory inputs. GABAB1<sup>-/-(orexin)</sup>mice exhibited severe fragmentation of sleep/wake states during both the light and dark periods without affecting total sleep time or inducing cataplexy, indicating that GABA<sub>B</sub> receptors are crucial regulators of orexin neurons and that "fine tuning" of orexin neurons by inhibitory and excitatory inputs is important for the stability of sleep/waking states. http://precedings.nature.com/documents/1195/version/1 oai:nature.com:10101/npre.2007.1195.1 http://hdl.handle.net/10101/npre.2007.1195.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1196.1 2007-10-01T20:53:14Z immunology molecular-cell-biology

Kinase independent inhibition of NFκB transcriptional activity by GRK5 through IκBα stabilization. 2007-09-29T07:20:40Z Daniela Sorriento Michele Ciccarelli Gaetano Santulli Alfonso Campanile Giovanna Giuseppina Altobelli Vincenzo Cimini Gennaro Galasso Dalila Astone Federico Piscione Lucio Pastore Bruno Trimarco Guido Iaccarino Immunology Molecular Cell Biology Members of the G protein receptor kinase (GRK) family that regulates receptor desensitization and members of the nuclear transcription factors family NF[kappa]B have been recently and convincingly demonstrated to interact, although the effects on transcription and gene expression have not yet been described. Using overexpression, knockdown (small interfering RNA) and mutagenesis experiments, we demonstrate that GRK5 couples to and stabilizes the NF[kappa]B inhibitor I[kappa]B[alpha], and inhibits NF[kappa]B activity. Studies with minigenes suggest that the N-terminal Regulation of G protein Signaling (RGS) homology (RH) domain confers GRK5 such ability. GRK5-RH domain overexpression affects NF[kappa]B dependent phenotypes, such as apoptosis protection, cytokine production and inflammation and tissue regeneration. Our results reveal a novel, unexpected role of GRK5 in NF[kappa]B transcription activity regulation that represents a possible target for diagnostic and therapeutics. http://precedings.nature.com/documents/1196/version/1 oai:nature.com:10101/npre.2007.1196.1 http://hdl.handle.net/10101/npre.2007.1196.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1198.1 2007-10-01T20:13:11Z biotechnology genetics molecular-cell-biology

Transient-mediated fate determination in a transcriptional circuit of HIV 2007-09-30T17:17:42Z Leor Weinberger Roy D. Dar Michael Simpson Biotechnology Genetics & Genomics Molecular Cell Biology Steady-state behavior and bistability have been proposed as mechanisms for decision-making in gene circuits. However, transient gene expression has also been proposed to control cell fate with the decision arbitrated by the lifetime of the expression transient. Here, we report that transcriptional positive-feedback plays a critical role in determining HIV infected cell-fate by extending the duration of Tat expression transients far beyond what protein half-life modulation can achieve. To directly quantify feedback strength and its effects on the duration of Tat transcriptional pulses, we exploit the noise inherent to gene-expression and measure shifts in the autocorrelation of expression noise. The results indicate that transcriptional positive-feedback extends the single-cell Tat expression lifetime by ~6-fold for both minimal Tat circuits and full-length, actively-replicating HIV-1. Importantly, artificial weakening of Tat positive-feedback shortened the duration of Tat expression transients and biased the probability in favor of latency. Thus, transcriptional positive-feedback appears to modulate transient expression lifetime and thereby control cell-fate in HIV. http://precedings.nature.com/documents/1198/version/1 oai:nature.com:10101/npre.2007.1198.1 http://hdl.handle.net/10101/npre.2007.1198.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1200.1 2007-10-02T08:55:41Z chemistry

Open Chemistry 2007-10-01T20:48:40Z Peter Murray-Rust Chemistry An invited article on Open Chemistry discussing the importance of Open Access and Open Data and stressing the emerging role of the blogosphere http://precedings.nature.com/documents/1200/version/1 oai:nature.com:10101/npre.2007.1200.1 http://hdl.handle.net/10101/npre.2007.1200.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1203.1 2007-10-03T14:27:44Z cancer molecular-cell-biology

Proapoptotic Bid Association with Mre11-Rad50-Nbs1 Complex is Indispensable for Checkpoint Activation after DNA Damage 2007-10-03T13:09:30Z Van B. T. Ta Karel Bezstarosti Jeroen A. A. Demmers Timurs Maculins Karlyn Schellekens Dik C. C. van Gent Stephan P. Persengiev Cancer Molecular Cell Biology The proapoptotic protein Bid is phosphorylated by ATM after double strand breaks (DSBs) induction and induces S-phase arrest by a mechanism that remains to be elucidated. Here we show that in mammalian cells, Bid is associated with Mre11, a subunit of the Mre11-Rad50-Nbs1 (MRN) complex. We demonstrate that Bid activation is abrogated in Mre11 and Nbs1 deficient primary mouse fibroblasts and cells from patients with ataxia talangiectasia-like disorder. Bid depletion by RNA interference inhibited the S-phase checkpoint activation and G2/M arrest after genotoxic insult, but had no effect on MRN complex formation. Our results explain the mechanism of Bid phosphorylation by ATM in response to DNA damage and suggest that Bid functions as a link between the MRN complex and S-phase regulatory proteins. http://precedings.nature.com/documents/1203/version/1 oai:nature.com:10101/npre.2007.1203.1 http://hdl.handle.net/10101/npre.2007.1203.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1204.1 2007-10-03T20:51:18Z microbiology

Antimicrobial activity of skin secretions isolated from Indian toad, Bufo melanostictus Schneider 1799 2007-10-03T20:05:19Z Abhishek Dinkarnath Garg Dattatrey V. Kanitkar Rajshekhar V. Hippargi Amit N. Gandhare Microbiology Amphibians like toads have been known to secrete antimicrobial secretions outside their body into their environments, through skin pores and parotid glands. Toad skin-secretions contain four types of compounds namely, biogenic amines, bufadienolides, alkaloids & steroids and peptides & proteins. Bulk of research relating to amphibian antimicrobial secretions has been done on frogs. In toads, such research has only been done in South America, Europe and China. Antimicrobial secretions vary considerably from specie-to-specie and drastically across various biomes. This prompted us to examine and confirm presence of antimicrobial activity (if any) in Indian Common Toad (Bufo melanostictus Schneider 1799) skin secretions since; no such analysis had been previously done on this toad which is found all across the South-east Asia. The antibacterial potency of toad skin secretions was tested against the bacteria, Escherichia coli. After running preliminary antibacterial analysis assays, we found that these cutaneous secretions retrieved from Indian Common Toad possessed potential bactericidal activity. The results that we got confirmed that some unexplored bactericidal components were present in skin secretions of these toads. These conclusions call for further research into biochemistry and molecular characterization of these components. http://precedings.nature.com/documents/1204/version/1 oai:nature.com:10.1038/npre.2007.1204.1 http://dx.doi.org/10.1038/npre.2007.1204.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1205.1 2007-10-03T21:13:40Z earth-and-environment

How Britain became an island 2007-10-03T20:33:44Z Philip Gibbard Earth & Environment Island Britain is separated from the European continent by the English Channel and the North Sea. But it was not always so. The floor of the Channel provides evidence for two catastrophic floods arising from the drainage of huge glacial lakes in the area of the southern North Sea. These megafloods carved the Dover Strait to make Britain the island it is today. http://precedings.nature.com/documents/1205/version/1 oai:nature.com:10.1038/npre.2007.1205.1 http://dx.doi.org/10.1038/npre.2007.1205.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1206.1 2007-10-04T08:32:42Z molecular-cell-biology

Activation of TRF3 Transcription Factor by Small Interfering RNAs 2007-10-04T06:58:25Z Stephan Persengiev Molecular Cell Biology RNA interference (RNAi) is a conserved biological response to double-stranded RNAs that results in posttranscriptional silencing of target gene expression. Double-stranded processed RNAs of 21-23 nt were found to affect in a non-specific manner a number of signaling and transcription pathways, including interferon and PKR cascades. We report here that siRNAs induce the expression of general transcription factor TRF3, which can trigger an interferon response in mammalian cells. http://precedings.nature.com/documents/1206/version/1 oai:nature.com:10.1038/npre.2007.1206.1 http://dx.doi.org/10.1038/npre.2007.1206.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1207.1 2007-10-05T08:53:31Z immunology

Bystander B cells rapidly acquire antigen receptors from activated B cells by membrane transfer: a novel mechanism for enhancing specific antigen presentation 2007-10-05T06:18:51Z Ben J. C. Quah Vaughan P. Barlow Virginia McPhun Klaus I. Matthaei Mark D. Hulett Christopher R. Parish Immunology The B cell antigen receptor (BCR) efficiently facilitates the capture and processing of a specific antigen for presentation on MHC class II molecules to antigen specific CD4+ T cells (1). Despite this, the majority of B cells are only thought to play a limited role in CD4+ T cell activation since BCRs are clonotypically expressed. Here we show, however, that activated B cells can, both in vitro and in vivo, rapidly donate their BCR to bystander B cells, a process that is mediated by direct membrane transfer between adjacent B cells and is amplified by the interaction of the BCR with specific antigen. This results in a dramatic expansion in the number of antigen-binding B cells in vivo, with the transferred BCR endowing recipient B cells with the ability to present specific antigen to antigen-specific CD4+ T cells. http://precedings.nature.com/documents/1207/version/1 oai:nature.com:10.1038/npre.2007.1207.1 http://dx.doi.org/10.1038/npre.2007.1207.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1208.1 2007-10-10T00:09:28Z biotechnology

Cell-free Embryonic Stem Cell Extract-mediated Derivation of Multi-potent Stem Cells from NIH3T3 Fibroblasts for Functional and Anatomical Ischemic Tissue Repair 2007-10-05T15:04:37Z Johnson Rajasingh Hiromichi Hamada Evelyn Bord Tina Thorne Ilona Goukassian Erin Lambers Prasanna Krishnamurthy Gangjian Qin Karen Schlauch Kenneth M. Rosen Deepali Ahluwalia Yan Zhu Douglas W. Losordo Raj Kishore Biotechnology The oocyte-independent generation of multipotent stem cells is one of the goals in regenerative medicine. We report that upon exposure to mouse ES cell (ESC) extracts, reversibly permeabilized NIH3T3 cells undergo de-differentiation followed by stimulus-induced re-differentiation into multiple lineage cell types. Genome-wide expression profiling revealed significant differences between NIH3T3 and ESC-extract treated NIH3T3 cells including re-activation of ESC specific transcripts. Epigenetically, ESC extracts induced CpG de-methylation of Oct4 promoter, hyper-acetylation of histones 3 and 4 and decreased lysine 9 (K-9) dimethylation of histone 3. In mouse models of surgically-induced hind limb ischemia (HLI) or acute myocardial infarction (AMI) transplantation of reprogrammed NIH3T3 cells significantly improved post-injury physiological functions and showed antomical evidence of engraftment and trans-differentiation into skeletal muscle, endothelial cell and cardiomyocytes. These data provide evidence for the generation of functional multi-potent stem like cells from terminally differentiated somatic cells without the introduction of trans-genes or ESC fusion. http://precedings.nature.com/documents/1208/version/1 oai:nature.com:10101/npre.2007.1208.1 http://hdl.handle.net/10101/npre.2007.1208.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1211.1 2007-10-09T09:33:23Z molecular-cell-biology

ACAT1, Cav-1, and PrP expression in brains and skin fibroblasts from Sarda breed sheep with scrapie-resistant and scrapie-susceptible genotype. 2007-10-08T10:02:06Z Alessandra Pani Marirosa Putzolu Claudia Mulas Cristina D. Orrù Claudia Abete Claudia Norfo M. Dolores Cannas Sergio Laconi Paolo La Colla Sandra Dessì Molecular Cell Biology Scrapie is an infective ovine neurodegenerative disease; the only identified component of the infectious agent being an aberrant isoform (PrPSc) of the cellular prion protein (PrPC). So far, no means for ante-mortem diagnosis are available for Scrapie as well as for any other mammal Transmissible Spongiform Encephalopaties. We recently found a strong relationship between cell susceptibility to scrapie-infection and intracellular cholesterol homeostasis alterations. In brain tissues as well as in ex vivo cultures of skin fibroblasts and PBMCs from healthy and scrapie-affected sheep carrying a scrapie-susceptible (ARQ/ARQ) genotype, the levels of cholesterol esters were consistently higher than in tissues and cultures derived from animals with a scrapie-resistant (ARR/ARR) genotype. Moreover, both uninfected and scrapie-affected ARQ/ARQ sheep showed abnormally low levels of high density lipoprotein-cholesterol (HDL-C) in their plasma, as compared to ARR/ARR animals. We now show that intracellular accumulation of cholesterol esters in fibroblasts derived from scrapie-susceptible sheep was accompanied by parallel alterations in the expression level of genes and gene products (ACAT1 and Cav-1) that are involved in the pathways leading to intracellular cholesterol esterification and trafficking. Comparative analysis of PrPc mRNA, showed an higher expression level in cells from animals carrying susceptible genotype, with or without Scrapie. Preliminary experiments also revealed the presence of PK-resistant PrP isoforms in the latter cultures. The data reported in the present paper suggest that accumulation of cholesterol esters in peripheral cells, together with the altered expression of some proteins implicated in intracellular cholesterol homeostasis, might serve to identify a distinctive lipid metabolic profile associated with increased susceptibility to develop prion disease following infection. http://precedings.nature.com/documents/1211/version/1 oai:nature.com:10101/npre.2007.1211.1 http://hdl.handle.net/10101/npre.2007.1211.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1212.1 2007-10-09T08:34:15Z immunology molecular-cell-biology

Upstream Stimulatory Factor (USF) and CCAAT/Enhancer Binding Protein δ (C/EBPδ) Compete for overlapping Sites in the Negative Regulatory Region of the HIV-1 LTR 2007-10-08T15:49:23Z Torik T. A. Ayoubi Sandra M. P. Meulemans Wim W. J. M. Van de Ven Immunology Molecular Cell Biology Human immunodeficiency virus type 1 (HIV-1) is a human retrovirus and the causative agent of the acquired immunodeficiency syndrome. Genetic analysis has revealed that the HIV-1 LTR contains a potential negative regulatory element (NRE) with an E box, the recognition sequence for the helix-loop-helix (HLH) family of transcription factors. Furthermore, the upstream stimulatory factor (USF) has been implicated as a negative regulator of HIV-1 expression. Here, we report that the NRE is a composite element and that both C/EBPδ and USF can specifically bind to the NRE. The recognition sequence for C/EBPδ overlaps with the E box in the NRE of HIV-1. Competition experiments showed that either USF or C/EBPδ binds to this NRE but not both together. http://precedings.nature.com/documents/1212/version/1 oai:nature.com:10.1038/npre.2007.1212.1 http://dx.doi.org/10.1038/npre.2007.1212.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1216.1 2007-10-11T14:18:31Z neuroscience

The sound of concepts: The link between auditory and conceptual brain systems 2007-10-10T08:42:08Z Markus Kiefer Eun-Jin Sim Bärbel Herrnberger Jo Grothe Klaus Hoenig Neuroscience Concepts in long-term memory are important building blocks of human cognition and are the basis for object recognition, language and thought. While it is well accepted that concepts are comprised of features related to sensory object attributes, it is still unclear how these features are represented in the brain. Of central interest is whether concepts are essentially grounded in perception. This would imply a common neuroanatomical substrate for perceptual and conceptual processing. Here we show using functional magnetic resonance imaging and recordings of event-related potentials that acoustic conceptual features rapidly recruit auditory areas even when implicitly presented through visual words. Recognizing words denoting objects for which acoustic features are highly relevant (e.g. "telephone") suffices to ignite cell assemblies in the posterior superior and middle temporal gyrus (pSTG/MTG) that were also activated by listening to real sounds. Activity in pSTG/MTG had an onset of 150 ms and increased parametrically as a function of acoustic feature relevance. Both findings suggest a conceptual origin of this effect rather than post-conceptual strategies such as imagery. The presently demonstrated link between auditory and conceptual brain systems parallels observations in other memory systems suggesting that modality-specificity represents a general organizational principle in cortical memory representation. The understanding of concepts as a partial reinstatement of brain activity during perception stresses the necessity of rich sensory experiences for concept acquisition. The modality-specific nature of concepts could also explain the difficulties in achieving a consensus about overall definitions of abstract concepts such as freedom or justice unless embedded in a concrete, experienced situation. http://precedings.nature.com/documents/1216/version/1 oai:nature.com:10101/npre.2007.1216.1 http://hdl.handle.net/10101/npre.2007.1216.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1218.1 2007-10-11T14:39:21Z molecular-cell-biology

Invariant mRNA content and mitotic protein breakdown as a solution to the Russian Doll problem of the mammalian cell cycle 2007-10-10T14:27:42Z Stephen Cooper Kerby Shedden Dang Vu-Phan Molecular Cell Biology It is widely accepted that numerous genes are expressed in a cell-cycle dependent manner, with cycle-specific variations in mRNA content or peaks of protein content during the cell cycle. These proposed variations raise the problem of how varying cell cycle gene expression is regulated. This is the "infinite regression" problem or Russian Doll problem where postulating a cell-cycle specific control element merely pushes the explanation of cell-cycle variation back one step to the problem of how that control element itself appears and disappears at particular times during the cell cycle. We present evidence that cyclin mRNA content is invariant during the cell cycle and calculations reveal that mRNA variation does not account for observed protein variations during the cell cycle. The experimental evidence for protein breakdown only at the end of the cell cycle leads to a general model for cell-cycle control that avoids the Russian Doll problem. http://precedings.nature.com/documents/1218/version/1 oai:nature.com:10101/npre.2007.1218.1 http://hdl.handle.net/10101/npre.2007.1218.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1219.1 2007-10-12T08:50:39Z biotechnology

A database of naturally occurring human urinary peptides and proteins for use in clinical applications 2007-10-11T07:09:33Z Petra Zürbig Joshua Coon Hartwig Bauer Georg Behrens Mohammed Dakna Anna Dominiczak Stephane Decramer Jochen Ehrich Danilo Fliser Moritz Frommberger Arnold Ganser Mark Giolami Igor Golovko David Good Wilfried Gwinner Marion Haubitz Stefan Herget-Rosenthal Holger Jahn George Jerums Bruce Julian Markus Kellmann Volker Kliem Walter Kolch Andrzej Krolewski Mario Luppi Ziad Massy Michael Melter Christian Neusüss Jan Novak Karlheinz Peter Kasper Rossing Harald Rupprecht Joost Schanstra Eric Schiffer Jens-Uwe Stolzenburg Lise Tarnow Dan Theodorescu Visith Thongboonkerd Raymond Vanholder Eva Weissinger Harald Mischak Philippe Schmitt-Kopplin Biotechnology Owing to its availability, ease of collection and correlation with (patho-) physiology, urine is an attractive source for clinical proteomics. However, the lack of comparable datasets from large cohorts has greatly hindered development in this field. Here we report the establishment of a high resolution proteome database of naturally occurring human urinary peptides and proteins - ranging from 800-17,000 Da - from over 3,600 individual samples using capillary electrophoresis coupled to mass spectrometry, yielding an average of 1,500 peptides per sample. All processed data were deposited in an SQL database, currently containing 5,010 relevant unique urinary peptides that serve as classifiers for diagnosis and monitoring of diseases, including kidney and vascular diseases. Of these, 352 have been sequenced to date. To demonstrate the applicability of this database, two examples of disease diagnosis were provided: For renal damage diagnosis, patients with a specific renal disease were identified with high specificity and sensitivity in a blinded cohort of 131 individuals. We further show definition of biomarkers specific for immunosuppression and complications after transplantation (Kaposi's sarcoma). Due to its high information content, this database will be a powerful tool for the validation of biomarkers for both renal and non-renal diseases. http://precedings.nature.com/documents/1219/version/1 oai:nature.com:10101/npre.2007.1219.1 http://hdl.handle.net/10101/npre.2007.1219.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1220.1 2007-10-12T10:00:56Z biotechnology

An intelligent liposome that may deliver drug molecules in a well controlled fashion 2007-10-11T08:34:26Z Dumitru Popescu Alin Gabriel Popescu Biotechnology The passage of molecules, especially large ones, through the cellular membrane is a very important problem for some biotechnological applications, such as drug delivery. The appearance of pores in the lipid bilayer following some controlled mechanisms may be an adequate and interesting way. Some pores, named stochastic pores, can appear due to structural and dynamic properties of lipid bilayer, but others may be favored by mechanical tension induced by different ways. Recently, a sequence of 30-40 pores was observed in the same vesicle, a pore at a time, which can appear in vesicles stretched by optical induced mechanical tension. There are two very interesting biotechnological applications that require the increase of membrane permeability: gene therapy and targeted drug delivery. In the first one, the transport of DNA fragments through cellular and nuclear membranes is required. The second application uses drug molecules encapsulated in vesicles, which have to be transported to a target place. Having reached that point, one supposes that the liposome discharges its content by its breakdown. In this paper, we will write about how a lipid vesicle has to release the drug molecules in a well-controlled fashion. Such liposomes are named pulsatory liposomes and they induce cyclic activity. We will demonstrate that this liposome may be programmed to work a certain number of cycles, settled in advance. Also, we will calculate the amount of drug delivered during each cycle. In fact, a pulsatory liposome may be conceived as a drug dose micro device, which works according to a medical prescription established _a priori_. http://precedings.nature.com/documents/1220/version/1 oai:nature.com:10101/npre.2007.1220.1 http://hdl.handle.net/10101/npre.2007.1220.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1225.1 2007-10-12T19:01:42Z bioinformatics

A quick trip through openness, freedom and transparency 2007-10-12T15:28:10Z Konrad U. Foerstner Bioinformatics This talk aims to give scientists an introduction to the concepts of openness, freedom and transparency and their applications (not only) for science. It covers the topics of open source, open formats, Creative Commons, open access, and open science/knowledge. A video of the talk is available on the author's website.
 http://precedings.nature.com/documents/1225/version/1 oai:nature.com:10.1038/npre.2007.1225.1 http://dx.doi.org/10.1038/npre.2007.1225.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1230.1 2007-10-16T19:57:23Z ecology genetics bioinformatics evolutionary-biology

EvolveAGene 3: A DNA coding sequence evolution simulation program 2007-10-16T19:00:19Z Barry G. Hall Ecology Genetics & Genomics Bioinformatics Evolutionary Biology EvolveAGene 3 is a realistic coding sequence simulation program that separates mutation from selection and allows the user to set selection conditions, including variable regions of selection intensity within the sequence and variation in intensity of selection over branches. Variation includes base substitutions, insertions and deletions. Output includes a log file, the true tree and both unaligned coding sequence and protein sequences and the true DNA and protein alignments. http://precedings.nature.com/documents/1230/version/1 oai:nature.com:10101/npre.2007.1230.1 http://hdl.handle.net/10101/npre.2007.1230.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1233.1 2007-10-18T13:38:25Z bioinformatics

Persistent BioPerl 2007-10-16T22:57:46Z Hilmar Lapp Bioinformatics I present BioSQL, a generic and highly extensible relational model for storing biological sequences, sequence clusters, genes, sequence features, sequence and feature annotation, and ontology terms. BioSQL also represents the interoperable persistence API among the Bio* life science programming toolkits (BioPerl, Biojava, Biopython, BioRuby), each of which has a language-binding to the BioSQL schema. I specifically present the Bioperl-db software, which in a transparent manner makes BioPerl objects persistent using BioSQL. http://precedings.nature.com/documents/1233/version/1 oai:nature.com:10.1038/npre.2007.1233.1 http://dx.doi.org/10.1038/npre.2007.1233.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1234.1 2007-10-17T16:08:42Z neuroscience

Semiotic Dynamics Solves the Symbol Grounding Problem 2007-10-17T11:04:12Z Luc L. Steels Martin Loetzsch Michael S. Spranger Neuroscience Language requires the capacity to link symbols (words, sentences) through the intermediary of internal representations to the physical world, a process known as symbol grounding. One of the biggest debates in the cognitive sciences concerns the question how human brains are able to do this. Do we need a material explanation or a system explanation? John Searle's well known Chinese Room thought experiment, which continues to generate a vast polemic literature of arguments and counter-arguments, has argued that autonomously establishing internal representations of the world (called 'intentionality' in philosophical parlance) is based on special properties of human neural tissue and that consequently an artificial system, such as an autonomous physical robot, can never achieve this. Here we study the Grounded Naming Game as a particular example of symbolic interaction and investigate a dynamical system that autonomously builds up and uses the semiotic networks necessary for performance in the game. We demonstrate in real experiments with physical robots that such a dynamical system indeed leads to a successful emergent communication system and hence that symbol grounding and intentionality can be explained in terms of a particular kind of system dynamics. The human brain has obviously the right mechanisms to participate in this kind of dynamics but the same dynamics can also be embodied in other types of physical systems. http://precedings.nature.com/documents/1234/version/1 oai:nature.com:10101/npre.2007.1234.1 http://hdl.handle.net/10101/npre.2007.1234.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1238.1 2007-10-18T16:44:46Z molecular-cell-biology

Collagen-bound low density lipoprotein modifies endothelial cell adhesion to type V collagen: Implications for atherosclerosis 2007-10-18T16:32:25Z Stefan Lorkowski Jürgen Rauterberg Bärbel Harrach-Ruprecht David Troyer Molecular Cell Biology Low density lipoprotein (LDL) is retained in the extracellular matrix of the arterial wall where it is considered to be atherogenic, but little is known about how cell adhesion to the matrix is affected by collagen-bound LDL. We tested the effect of native, oxidized and acetylated LDL reacted with adsorbed monomeric type I, III and V collagen on endothelial cell adhesion to collagen using a colorimetric adhesion assay. We found that none of the LDL species affected adhesion to type I and III collagen, but that collagen-bound native and acetylated LDL enhanced attachment to type V collagen, whereas bound oxidized LDL inhibited adhesion to this collagen. We suggest that oxidized LDL associated with type V collagen in the arterial wall would favor de-endothelialization and contribute to atherogenesis and thrombosis. http://precedings.nature.com/documents/1238/version/1 oai:nature.com:10.1038/npre.2007.1238.1 http://dx.doi.org/10.1038/npre.2007.1238.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1239.1 2007-10-23T15:06:12Z chemistry pharmacology bioinformatics

Side effect profile prediction - Tackling Big Pharma's worst nightmare at an early stage 2007-10-18T21:10:57Z Josef Scheiber Chemistry Pharmacology Bioinformatics This talk presents a method that predicts adverse side effects for molecules based on the chemical structure only. Also, targets for the compounds are predicted. Therefore it becomes possible to link a certain side effect to the interaction with a certain target through molecular space. Examples are given in the talk. http://precedings.nature.com/documents/1239/version/1 oai:nature.com:10.1038/npre.2007.1239.1 http://dx.doi.org/10.1038/npre.2007.1239.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1240.1 2007-10-19T09:20:18Z earth-and-environment

A century of warfare shoots holes in anti-Caulerpa campaign 2007-10-18T23:01:09Z John R. M. Chisholm Pavel P. Povinec Valerie Briet Janine Gastaud Jean M. Jaubert Sang-Han Lee Isabelle Levy-Palomo Manuel Marchioretti Audrey Minghelli-Roman Earth & Environment Effort to have all varieties of the marine alga Caulerpa taxifolia listed as noxious weeds hinges on the argument that the alga's proliferation in the Mediterranean Sea is a cause and not a consequence of environmental degradation. Until now, the occurrence of two populations in a pristine part of the northern Mediterranean near the island of Porquerolles has upheld this claim. Here we show that the alga's development at Porquerolles is indeed a consequence of environmental degradation caused by military weapons' impacts on seagrass beds during the last century. The available data show that substratum enrichment plays a key role in fostering development of Caulerpa, irrespective of whether this results directly from pollution or from the impacts of pollution and other anthropogenic factors on benthic vegetation cover. http://precedings.nature.com/documents/1240/version/1 oai:nature.com:10.1038/npre.2007.1240.1 http://dx.doi.org/10.1038/npre.2007.1240.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.907.2 2007-10-19T19:42:22Z cancer ecology

Homologous self-organising scale-invariant properties characterise long range species spread and cancer invasion 2007-10-19T12:31:32Z Diana E. Marco Sergio A. Cannas Marcelo A. Montemurro Bo Hu Shi-Yuan Cheng Cancer Ecology Occupancy of new habitats through dispersion is a central process in nature. In particular, long distance dispersal is involved in the spread of species and epidemics, although it has not been previously related with cancer invasion, a process that involves cell spreading to tissues far away from the primary tumor.

Using simulations and real data we show that the early spread of cancer cells is similar to the species individuals spread and that both processes are represented by a common spatio-temporal signature of long-distance dispersal and subsequent local proliferation. This signature is characterized by a particular fractal geometry of the boundaries of patches generated, and a power law-scaled, disrupted patch size distribution. In contrast, invasions involving only dispersal but not subsequent proliferation (“physiological invasions”) like trophoblast cells invasion during normal human placentation did not show the patch size power law pattern. Our results are robust to temporal and spatial scales, and to the resolution level of analysis.

We conclude that the scaling properties are a hallmark and a direct result of long-distance dispersal and proliferation, and that they reflect homologous ecological processes of population self-organization during cancer and species spread. Our results are significant for the detection of processes involving long-range dispersal and proliferation like cancer metastasis, biological invasions and epidemics, and for the formulation of new cancer therapeutical approaches.
 http://precedings.nature.com/documents/907/version/2 oai:nature.com:10101/npre.2007.907.2 http://hdl.handle.net/10101/npre.2007.907.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1241.1 2007-10-19T15:07:14Z biotechnology neuroscience

On Real-Time Synthetic Primate Vision 2007-10-19T14:01:58Z Andrew A. Dankers Nick Barnes Walter F. Bischof Alex Zelinsky Biotechnology Neuroscience The primate vision system exhibits numerous capabilities. Some important basic visual competencies include: 1) a consistent representation of visual space across eye movements; 2) egocentric spatial perception; 3) coordinated stereo fixation upon and pursuit of dynamic objects; and 4) attentional gaze deployment. We present a synthetic vision system that incorporates these competencies.We hypothesize that similarities between the underlying synthetic system model and that of the primate vision system elicit accordingly similar gaze behaviors. Psychophysical trials were conducted to record human gaze behavior when free-viewing a reproducible, dynamic, 3D scene. Identical trials were conducted with the synthetic system. A statistical comparison of synthetic and human gaze behavior has shown that the two are remarkably similar. http://precedings.nature.com/documents/1241/version/1 oai:nature.com:10101/npre.2007.1241.1 http://hdl.handle.net/10101/npre.2007.1241.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1243.1 2007-10-23T17:07:55Z ecology bioinformatics evolutionary-biology

Estimation of DNA Sequence Context-dependent Mutation Rates Using Primate Genomic Sequences: Application to Estimation of Selection Bias in Protein (Human TP53) Evolution 2007-10-19T18:28:27Z Wei Zhang Ecology Bioinformatics Evolutionary Biology Understanding of the mechanism of DNA mutation process is critical for studying the functional consequences of genetic variation in clinical medicine (eg. drug response) as well as other complex traits (eg. gene expression and cause of common diseases). During the last several decades, many probabilistic models of DNA nucleotide substitution have been proposed for studying this process. A common feature of these mutation models is that they assume the nucleotides evolve independently at each site. In other words, they are sequence context-independent models. However, based on various biochemical studies, it is now recognized that the DNA mutation process resulting in substitutions in both coding and non-coding regions may depend on sequence context. We proposed here a more realistic sequence context-dependent mutation model, which could contribute to the better understanding of the DNA mutation spectrum in genomes.We also showed its application to protein evolution by separating the mutation bias and selection bias in amino acid substitutions.
 http://precedings.nature.com/documents/1243/version/1 oai:nature.com:10.1038/npre.2007.1243.1 http://dx.doi.org/10.1038/npre.2007.1243.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1244.1 2007-10-24T16:33:49Z neuroscience

A new dynamic property of human consciousness 2007-10-20T15:29:04Z UnCheol Lee Seunghwan Kim Gyu-Jeong Noh Byung-Moon Choi Neuroscience As pointed out by William James, "the consciousness is a dynamic process, not a thing" , during which short term integration is succeeded by another differentiated neural state through the continual interplay between the environment, the body, and the brain itself. Thus, the dynamic structure underlying successive states of the brain is important for understanding human consciousness as a process. In order to investigate the dynamic property of human consciousness, we developed a new method to reconstruct a state space from electroencephalogram(EEG), in which a trajectory, reflecting states of consciousness, is constructed based on the global information integration of the brain. EEGs were obtained from 14 subjects received an intravenous bolus of propopol. Here we show that the degree of human consciousness is directly associated with the information integration capacity of gamma wave, which is significantly higher in the conscious state than in the unconscious state. And we found a new time evolutional property of human consciousness. The conscious state showed a lower dimensional dynamic process which changed to a random-like process after loss of consciousness. This characteristic dynamic property, appeared only in the gamma band, might be used as an indicator to distinguish the conscious and unconscious states and also considered as an important fact for the human consciousness model. http://precedings.nature.com/documents/1244/version/1 oai:nature.com:10101/npre.2007.1244.1 http://hdl.handle.net/10101/npre.2007.1244.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1246.1 2007-11-08T10:41:33Z molecular-cell-biology neuroscience

Changes in Cholesterol Metabolism in Peripheral Cells of Alzheimer Disease Patients and Their Relatives 2007-10-23T08:02:42Z Alessandra Pani Paolo La Colla Claudia Abete Claudia Mulas Marirosa Putzolu Claudia Norfo Sergio Laconi Anna Borgia Christina Zaru Manuela Palmas Paolo F. Putzu Alessandra Mocali Francesco Paoletti Sandra Dessi Molecular Cell Biology Neuroscience Background. Previous epidemiological and experimental studies indicated cholesterol as a central player in Alzheimer disease (AD). Here, we utilized skin fibroblasts and PBMC as possible ex vivo models for the study of dysfunctions of cholesterol homeostasis which may be related to AD development. 
Methods. We analyzed cholesterol homeostasis using colorimetric, thin layer chromatography (TLC), and histologic technique in ex vivo cultures of skin fibroblasts and PBMCs from patients with probable AD and their first-degree relatives. Additionally, healthy age-matched individuals served as controls. 
Findings. As compared to controls, skin fibroblasts and PBMCs from AD patients, displayed an evident alteration of cholesterol metabolism; namely an anomalous accumulation of cholesterol esters in their cytoplasm. No change in intracellular free cholesterol was observed. Cellular overloading of cholesterol esters was dramatically increased after specific growth stimulation of the different cell types. Cholesterol ester accumulation was negatively correlated to plasma levels of high density lipoprotein cholesterol (HDL-C) and positively correlated with severity of cognitive symptoms measured by Mini-Mental State Examination (MMSE). Inhibitors of cholesterol esterification, such as progesterone and SaH, as well as a potent inhibitor of cell proliferation, RAD, were able to prevent accumulation of cholesterol esters. 
Interpretation. Changes of cholesterol esters in the peripheral compartment may be indicative of a systemic alteration of intracellular cholesterol homeostasis, which in turn might create a cellular milieu favourable to the production of ß-amyloid in the brain. Pathways that control cholesterol esterification might represent promising targets for novel diagnostic and therapeutic AD approaches.
 http://precedings.nature.com/documents/1246/version/1 oai:nature.com:10101/npre.2007.1246.1 http://hdl.handle.net/10101/npre.2007.1246.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1248.1 2007-10-23T15:17:56Z microbiology molecular-cell-biology bioinformatics

Internal ribosomal entry site lacks secondary structure 2007-10-23T14:28:30Z Xuhua Xia Microbiology Molecular Cell Biology Bioinformatics The search for mechanisms of translational regulation has yielded many experimentally identified internal ribosome entry sites (IRES). Because of the lack of sequence similarity among the experimentally IRESs, it is widely assumed that IRESs posses stable secondary structure allowing them to interact with the components of the translation machinery. Contrary to this view, here we show that IRES activity in nine yeast IRESs, mapped to 60 nt immediately upstream of the initiation AUG, is strongly associated with the lack of secondary structure of IRESs. Furthermore, the reverse complements of these IRESs, with their secondary structure more stable than those of the IRESs, exhibit little IRES activity. The generality of this association is exemplified by the observation that, in the natural _vpu-env_ bicistronic mRNA in HIV-1, the mRNA segment (60 nt) immediately upstream of the initiation AUG of _env_ has the weakest secondary structure among all dominant HIV-1 mRNA species. These results suggest a unified model of alternative translation initiation. http://precedings.nature.com/documents/1248/version/1 oai:nature.com:10101/npre.2007.1248.1 http://hdl.handle.net/10101/npre.2007.1248.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1249.1 2007-10-24T09:11:06Z biotechnology genetics microbiology

A Simple, Rapid Method for Extracting Large Plasmid DNA from Bacteria 2007-10-23T21:58:04Z Spencer D. Heringa Jonathan D. Monroe James B. Herrick Biotechnology Genetics & Genomics Microbiology We are studying the lateral transfer of transmissible antibiotic resistance plasmids among stream bacteria impacted by fecal runoff from poultry and cattle. Such plasmids are typically large (ca. 40 – 100 kb) and occur in low copy numbers in the cell and have therefore typically been difficult to isolate and therefore to study. Traditional protocols, based upon variations of the standard alkaline-lysis method, are long (ca. 1 1/2 to 2 days) and difficult. Commercial kits designed for the isolation of Baterial Artificial Chromosomes (BACs) can be used and are an improvement; however, these are expensive and still require hours of sustained effort. We have adapted a method published by Rondon et al. (1999), originally designed for the isolation of BAC DNA, for the rapid isolation of large plasmid DNA. In this method, lysis and alkaline denaturation steps are combined, incubation steps are vastly reduced, proteins are removed via a simple ammonium acetate/chloroform step, and the DNA precipitated using a plyethylene glycol/NaCl step. No ethanol precipitation is required. If additional purification is required, extracted DNA can be further processed through a Qiagen Plasmid Mini or Midi column (Qiagen Inc., Valencia CA). The method is rapid (under 1 hour), easy, very inexpensive and has been reliably used by undergraduate students to isolate large (up to 200 kb) native plasmids from a variety of both Gram-positive and Gram-negative genera including _Shigella_, _Klebsiella_, _E. coli_, _Pseudomonas_, _Bacills_, _Streptococcus_, _Staphylococcus_, and _Enterococcus_, as well as BACs from _E. coli_. The protocol is simple and reliable enough to be used for the rapid large-scale visualization of native plasmids and we have used it to visualize and isolate DNA from hundreds of multidrug resistance plasmids exogenously captured from stream sediments, soils, and beach sands.
 http://precedings.nature.com/documents/1249/version/1 oai:nature.com:10.1038/npre.2007.1249.1 http://dx.doi.org/10.1038/npre.2007.1249.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1250.1 2007-10-24T13:56:31Z biotechnology cancer immunology

Artificial Antigen Presenting Cells With Preclustered anti-CD28/-CD3/-LFA-1 Monoclonal Antibodies Are Highly Effective To Induce The Ex-Vivo Expansion Of Functional Human Antitumor T Cells 2007-10-24T10:43:46Z Roberta Zappasodi Massimo Di Nicola Carmelo Carlo-Stella Roberta Mortarini Alessandra Molla Claudia Vegetti Lorena Passoni Salvatore Albani Andrea Anichini Alessandro M. Gianni Biotechnology Cancer Immunology Effective adoptive T cell therapy requires the _ex vivo_ generation of functional T lymphocytes with a long lifespan _in vivo_. We evaluated _in vitro_ T cell expansion by artificial antigen presenting cells (aAPC) generated with activating (human anti-CD3), co-stimulating (human anti-CD28) and adhesion (human anti-LFA-1) monoclonal antibodies pre-clustered in microdomains (MDs) held by a liposome scaffold. The co-localization of T cell ligands in MDs and the targeting of an adhesion protein, increasing the efficiency of immunological synapse formations, represent the novelties of our system. These aAPCs allowed increased expansion of polyclonal CD4^+^ and CD8^+^ T cells and of tumor antigen-specific CD8^+^ T cells compared to anti-CD28- and anti-CD3-coated microbeads and to immobilized anti-CD3. These aAPCs allowed the generation of T cells displaying an immunophenotype consistent with long-term _in vivo_ persistence, without increasing the frequency of regulatory T cells. Finally, our aAPCs proved to be suitable for large scale T cell expansion required in immunotherapy trials. http://precedings.nature.com/documents/1250/version/1 oai:nature.com:10101/npre.2007.1250.1 http://hdl.handle.net/10101/npre.2007.1250.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1251.1 2007-10-25T18:49:12Z biotechnology bioinformatics

Discovery of transcription factor binding sites through integration of generic motif finders 2007-10-25T09:49:09Z Edward Wijaya Siu-Ming Yiu Thanh Son Ngo Rajaraman Kanagasabai Wing-Kin Sung Biotechnology Bioinformatics Locating transcription factor binding sites is a key step in understanding gene regulation. Due to its importance, many _de novo_ motif-finding methods have been proposed. Individually, these motif finders perform unimpressively overall based on Tompa's benchmark datasets. Moreover, these motif finders vary in their definitions of what constitute a motif, and in their methods for finding statistically overrepresented motifs. There is no clear way for biologists to choose the motif finder that is most suitable for their task. The purpose of this work is to describe a method called MotifVoter to identify transcription factor binding sites by integrating the results found by motif finders of different models. Validation of our method on Tompa's benchmark, real metazoan and _E. coli_ datasets show that it can improve the sensitivity significantly without sacrificing the precision. Our approach offers a practical alternative for biologists to study novel transcription factors.
The MotifVoter software is available for public use at: http://www.comp.nus.edu.sg/~bioinfo/MotifVoter http://precedings.nature.com/documents/1251/version/1 oai:nature.com:10101/npre.2007.1251.1 http://hdl.handle.net/10101/npre.2007.1251.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1254.1 2007-10-25T19:33:10Z neuroscience

Beyond Spike Timing Theory – Thermodynamics of Neuronal Computation 2007-10-25T14:56:26Z Dorian Aur Mandar S. Jog Neuroscience This paper highlights ionic fluxes as information carriers in neurons. The theoretical framework regarding information transfer is presented as changes in the thermodynamic entropy that underlie specific computations determined by ionic flow. The removal or accumulation of information is analyzed in terms of ionic mass transfer related with changes in Shannon information entropy. Specifically, information transfer occurs during an action potential (AP) via the voltage gated ion channels in membranes and the same physical mechanism can be extended to various types of synapses. Since sequential APs from a selected neuron are not alike, then every spike may transfer slightly different amounts of information during their occurrence. The average efficiency in information transfer during APs is estimated using mutual information measures and Hodgkin-Huxley model. This general scheme of ions as carriers of information represents the required physical machinery for a dynamic information transfer that is missing in the current spike-timing description. http://precedings.nature.com/documents/1254/version/1 oai:nature.com:10101/npre.2007.1254.1 http://hdl.handle.net/10101/npre.2007.1254.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.58.2 2007-11-05T16:05:47Z bioinformatics

Systems Biology Markup Language (SBML) Level 2: Structures and Facilities for Model Definitions 2007-10-26T08:21:04Z Michael Hucka Andrew M. Finney Stefan Hoops Sarah M. Keating Nicolas Le Novere Bioinformatics With the rise of Systems Biology as a new paradigm for understanding biological processes, the development of quantitative models is no longer restricted to a small circle of theoreticians. The dramatic increase in the number of these models precipitates the need to exchange and reuse both existing and newly created models. The Systems Biology Markup Language (SBML) is a free, open, XML-based format for representing quantitative models of biological interest that advocates the consistent specification of such models and thus facilitates both software development and model exchange.

Principally oriented towards describing systems of biochemical reactions, such as cell signalling pathways, metabolic networks and gene regulation etc., SBML can also be used to encode any kinetic model. SBML offers mechanisms to describe biological components by means of compartments and reacting species, as well as their dynamic behaviour, using reactions, events and arbitrary mathematical rules. SBML also offers all the housekeeping structures needed to ensure an unambiguous understanding of quantitative descriptions.

This specification presents the structures of the language and the rules used to build a valid model. SBML XML Schema and other related documents and software are also available from the SBML project web site, "http://sbml.org/":http://sbml.org/. http://precedings.nature.com/documents/58/version/2 oai:nature.com:10101/npre.2007.58.2 http://hdl.handle.net/10101/npre.2007.58.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1258.1 2007-10-26T14:39:34Z ecology neuroscience

Cognitive dimensions of predator responses to imperfect mimicry? 2007-10-26T11:51:32Z Lars Chittka Daniel Osorio Ecology Neuroscience Many palatable insects, for example hoverflies, deter predators by mimicking well-defended insects such as wasps. However, for human observers, these flies often seem to be little better than caricatures of wasps – their visual appearance and behaviour are easily distinguishable. This imperfect mimicry baffles evolutionary biologists, because one might expect natural selection to do a more thorough job. Here we discuss two types of cognitive processes that might explain why mimics distinguishable mimics might enjoy increased protection from predation. Speed accuracy tradeoffs in predator decision making might give imperfect mimics sufficient time to escape, and predators under time constraint might avoid time-consuming discriminations between well-defended models and inaccurate edible mimics, and instead adopt a “safety first” policy of avoiding insects with similar appearance. Categorization of prey types by predators could mean that wholly dissimilar mimics may be protected, provided they share some common property with noxious prey. http://precedings.nature.com/documents/1258/version/1 oai:nature.com:10101/npre.2007.1258.1 http://hdl.handle.net/10101/npre.2007.1258.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1259.1 2007-10-26T15:22:33Z biotechnology

Optimising Blue Fluorescent Protein (BFP) for use as a mammalian reporter gene in parallel with Green Fluorescent Protein (GFP). 2007-10-26T12:05:43Z Etienne Joly Biotechnology To obtain an optimised form of BFP for use as a reporter gene in mammalian cells, the brightest available GFP form, EGFP, was mutated at 5 different positions, yielding 8 different mutagenised forms of BFP. The intensity of the fluorescent signals attained in mammalian cells with all these various versions of BFP was analysed by flow cytometry of transiently transfected COS 7 cells. The best mutant obtained can be detected readily both by flow cytometry and fluorescence microscopy, even when expressed together with GFP. To explore whether cellular localization could enhance the fluorescence signals any further, plasmid constructs were made to target optimised versions of GFP and BFP to the nucleus, the endoplasmic reticulum (ER) and the cell surface. Expression in the nucleus or ER increased the fluorescence signal by ca. 50%, whereas cell surface expression resulted in a five-fold decrease compared to the ER and nuclear forms. Co-expression of GFP and BFP in the same cellular compartment did not result in any significant absorption of the blue fluorescence by GFP. Thus, targeting of GFP and BFP to various cellular compartments adds even further versatility to this convenient dual reporter-gene system. http://precedings.nature.com/documents/1259/version/1 oai:nature.com:10101/npre.2007.1259.1 http://hdl.handle.net/10101/npre.2007.1259.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1260.1 2007-10-29T17:13:16Z neuroscience

Reciprocal homeostatic reactions to chronic excitatory synaptic receptor inactivation in developing cerebral cortex networks 2007-10-26T14:19:04Z Michael A. Corner Neuroscience Chronic blockade of actively excitatory glutamatergic synaptic receptors in co-cultured organotypic rodent neocortex explants leads to a compensatory up-regulation of otherwise inactive input channels so as to maintain almost normal levels of ongoing bursts of action potentials. We report here that this homeostatic return of spontaneous (now kainate receptor driven) firing is accompanied by a reciprocal down-regulation of blocked AMPA and NMDA receptors, such that the developing cortical network is protected against becoming hyperactive when those synaptic inputs are again able to transmit normally. http://precedings.nature.com/documents/1260/version/1 oai:nature.com:10101/npre.2007.1260.1 http://hdl.handle.net/10101/npre.2007.1260.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1263.1 2007-10-29T10:42:34Z biotechnology ecology microbiology

_Streptomyces_ sp. as predators of bacteria 2007-10-27T11:55:23Z Charushila A. Kumbhar Milind G. Watve Biotechnology Ecology Microbiology Background: The ecological role of actinomycetes and their secondary metabolites is not yet completely understood. 
Hypothesis: Actinomycetes and Streptomyces sp. in particular, are non-obligate predators of bacteria in soil. 
Evidence: Ability to grow on live bacterial cells as a sole source of nutrients. Prey cell lysis accompanying growth. Circumstantial evidence for the involvement of antimicrobials along with enzymes.
Implications: This finding may open up a new source of novel secondary metabolites from the genus. http://precedings.nature.com/documents/1263/version/1 oai:nature.com:10.1038/npre.2007.1263.1 http://dx.doi.org/10.1038/npre.2007.1263.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1269.1 2007-10-31T11:11:40Z neuroscience

Neural activity dissociation between thought-based and perception-based response conflict 2007-10-28T06:45:49Z Antao Chen Xu Lei Xiting Huang Qinglin Zhang Qiang Liu Yongxiu Lai Dezhong Yao Hong Li Neuroscience Based on the idea that intentions have different penetrability to perception and thought (Fodor, 1983), four Stroop-like tasks, AA, AW, WA, and WW are used, where the A represents an arrow and the CPPR (closest processing prior to response) is perception, and the W represents a word and the CPPR is thought. Event-related brain potentials were recorded as participants completed these tasks, and sLORETA (standardized low resolution brain electromagnetic tomography) was used to localize the sources at specific time points. These results showed that there is an interference effect in the AA and WA tasks, but not in the AW or WW tasks. The activated brain areas related to the interference effect in the AA task were the PFC and ACC, and PFC activation took place prior to ACC activation; but only PFC in WA task. Combined with previous results, a new neural mechanism of cognitive control is proposed. http://precedings.nature.com/documents/1269/version/1 oai:nature.com:10101/npre.2007.1269.1 http://hdl.handle.net/10101/npre.2007.1269.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1272.1 2007-10-29T14:57:50Z ecology plant-biology evolutionary-biology

Age and origin of enigmatic megaherbs from the subantarctic islands 2007-10-28T20:54:48Z Steven J. Wagstaff Ilse Breitwieser Christopher Quinn Motomi Ito Ecology Plant Biology Evolutionary Biology Biogeographic relationships in the southern hemisphere have puzzled biologists for the last two centuries. Once joined to form the supercontinent Gondwana, Africa, Antarctica, Australia, New Zealand and South America are widely separated by the Pacific and Indian oceans. Sir Joseph Hooker was the first to suggest that Antarctica served as a corridor for plant migration not unlike the land-bridges in the northern hemisphere. While the Antarctic flora was largely erased by glaciation during the Pleistocene, at least some of these Antarctic plant communities found refuge on the subantarctic islands. Here we provide support for the hypothesis that giant herbs persisted in the subantactic islands prior to the onset of Pleistocene glaciation, then dispersed northward in response to glacial advance. Our findings provide further evidence that Antarctica has played a pivotal role in shaping southern hemisphere biogeography. http://precedings.nature.com/documents/1272/version/1 oai:nature.com:10101/npre.2007.1272.1 http://hdl.handle.net/10101/npre.2007.1272.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.980.2 2007-11-12T16:48:34Z bioinformatics

The Normal Fetal Heart Rate Study: Analysis Plan 2007-10-29T12:39:10Z Martin Daumer Michael Scholz Anne-Laure Boulesteix Stephanie Pildner von Steinburg Sven Schiermeier Wolfgang Hatzmann K T M Schneider Bioinformatics Recording of fetal heart rate via CTG monitoring has been routinely performed as an important part of antenatal and subpartum care for several decades. The current guidelines of the FIGO (ref1) recommend a normal range of the fetal heart rate from 110 to 150 bpm. However, there is no agreement in the medical community whether this is the correct range (ref2). We aim to address this question by computerized analysis (ref 3) of a high quality database (HQDb, ref 4) of about one billion electronically registered fetal heart rate measurements from about 10,000 pregnancies in three medical centres over seven years. In the present paper, we lay out a detailed analysis plan for this evidence-based project in the vein of the validation policy of the Sylvia Lawry Centre for Multiple Sclerosis Research (ref 5) with a split of the database into an exploratory part and a part reserved for validation. We will perform the analysis and the validation after publication of this plan in order to reduce the probability of publishing false positive research findings (ref 6-7). http://precedings.nature.com/documents/980/version/2 oai:nature.com:10.1038/npre.2007.980.2 http://dx.doi.org/10.1038/npre.2007.980.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1275.1 2007-10-29T17:27:08Z earth-and-environment

French birds lag behind climate warming 2007-10-29T15:34:21Z Vincent Devictor Romain Julliard Denis Couvet Frédéric Jiguet Earth & Environment Biodiversity responses to climate warming have been documented through the study of changes in distributions, abundances or phenologies of individual species or in more integrated measures such as species community richness and composition. However, whether these observed population and community changes are occurring fast enough to cope with new climatic conditions remain uncertain and hardly quantifiable. Here, using spatial and temporal trends from the French breeding bird survey, we show that although bird assemblages are strongly responding to climate warming, this response is slower than expected for catching up with the current temperature increase. During the last two decades, French birds have only achieved 54% of the response required to follow temperature increase, and have accumulated, in 18 years, a 97 km delay in their northward shift. We thus developed a framework to measure both the observed and predicted response of species assemblage to climate change, an approach which is flexible enough to be applicable to any taxa with large-scale survey data, using either abundance or distribution data. For example, it can be further used to test if different delays are found across groups or if, for a given group, the delay depends on the land-use contexts. http://precedings.nature.com/documents/1275/version/1 oai:nature.com:10101/npre.2007.1275.1 http://hdl.handle.net/10101/npre.2007.1275.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1276.1 2007-10-29T17:50:53Z genetics evolutionary-biology

Discovery of the Principal Cystic Fibrosis Mutation (F508del) in Ancient DNA from Iron Age Europeans 2007-10-29T17:17:34Z Philip Farrell Cedric Le Marechal Claude Ferec Malika Siker Maria Teschler-Nicola Genetics & Genomics Evolutionary Biology The most common, life-threatening autosomal recessive disease of Europeans and Euro-Americans, cystic fibrosis (CF), occurs predominately in patients with the F508del mutation.1 Although F508del is currently detectable as a single allele in 1/30-1/40 Europeans2-4 and Euro-Americans,5 it has not been determined what heterozygote selective advantage(s) might account for its relatively high prevalence. Indirect evidence6 suggests that this mutation was present in Brittany at least 3000 years ago, but no direct analyses of ancient DNA have been reported to identify F508del and clarify its frequency in prehistoric inhabitants of Europe. Here we show that F508del was present in 3 of 32 Iron Age inhabitants of Austria from whom DNA could be recovered from molar teeth using procedures that fulfill authenticity criteria.7 Because these individuals, who were buried in cemeteries along the Danube river, were shown by radiocarbon dating of isolated bone collagen to have lived there during 544-255 BC, this indicates that the F508del mutation is definitely more than 2000 years old and that CF (the disease) was present among them. More generally, the apparent enrichment of this Iron Age population in F508del suggests an evolutionary advantage in their environment that can be investigated by interdisciplinary strategies of paleoepidemiology. http://precedings.nature.com/documents/1276/version/1 oai:nature.com:10101/npre.2007.1276.1 http://hdl.handle.net/10101/npre.2007.1276.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1278.1 2007-10-30T19:40:59Z ecology

The oldest amputation on a Neolithic human skeleton in France 2007-10-29T19:26:50Z Cecile Buquet-Marcon Charlier Philippe Samzun Anaick Ecology While 'surgical' practices such as trepanations are well attested since the first stages of the European Neolithic, the amputation of limbs in Prehistoric periods has not been well-documented until the case presented here. The particularly well-preserved remains of an aged male were recently uncovered in the Neolithic site (4900-4700 BC) of Buthiers-Boulancourt in the vicinity of Paris, France. It was already noticed in situ that the distal part of the left humerus was abnormal and this led us to the hypothesis of a partially healed 'surgical' amputation.The further investigations reported here confirm a traumatic origin and a partial cicatrisation after surgery, indicating that the patient survived. It also proves the remarkable medical skills developed during Prehistorical times. In addition, the associated grave goods are original, including the skeleton of an animal, a polished schist axe and a massive 30 cm long flint pick. Despite the serious handicap from which he suffered in this pastoral-agricultural community, the buried man obviously enjoyed some particular social status, as suggested by the remarkable and 'prestigious' accompanying grave-goods. If indeed this man benefited from some form of community care, this would indicate the level of social solidarity in Western Europe almost 7000 years ago. http://precedings.nature.com/documents/1278/version/1 oai:nature.com:10101/npre.2007.1278.1 http://hdl.handle.net/10101/npre.2007.1278.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1260.2 2007-11-06T09:53:34Z neuroscience

Reciprocal homeostatic reactions to chronic excitatory synaptic receptor inactivation in developing cerebral cortex networks 2007-10-29T21:55:54Z Michael A. Corner Neuroscience Chronic blockade of actively excitatory glutamatergic synaptic receptors in co-cultured organotypic rodent neocortex explants leads to a compensatory up-regulation of otherwise inactive input channels so as to maintain almost normal levels of ongoing bursts of action potentials. We report here that this homeostatic return of spontaneous (now kainate receptor driven) firing is accompanied by a reciprocal down-regulation of blocked AMPA and NMDA receptors, such that the developing cortical network is protected against becoming hyperactive when those synaptic inputs are again able to transmit normally. http://precedings.nature.com/documents/1260/version/2 oai:nature.com:10.1038/npre.2007.1260.2 http://dx.doi.org/10.1038/npre.2007.1260.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1263.2 2007-11-01T17:00:03Z biotechnology ecology microbiology

_Streptomyces_ sp. as predators of bacteria 2007-10-30T14:36:26Z Charushila A. Kumbhar Milind G. Watve Biotechnology Ecology Microbiology Background: The ecological role of actinomycetes and their secondary metabolites is not yet completely understood. 
Hypothesis: Actinomycetes and Streptomyces sp. in particular, are non-obligate predators of bacteria in soil. 
Evidence: Ability to grow on live bacterial cells as a sole source of nutrients. Prey cell lysis accompanying growth. Circumstantial evidence for the involvement of antimicrobials along with enzymes.
Implications: This finding may open up a new source of novel secondary metabolites from the genus. http://precedings.nature.com/documents/1263/version/2 oai:nature.com:10.1038/npre.2007.1263.2 http://dx.doi.org/10.1038/npre.2007.1263.2 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1281.1 2007-10-31T21:20:37Z molecular-cell-biology bioinformatics

Reactome - a knowledgebase of human biological pathways 2007-10-30T20:56:53Z Peter D'Eustachio David Croft Bernard de Bono Gopal Gopinath Marc Gillespie Bijay Jassal Lisa Matthews Esther Schmidt Imre Vastrik Guanming Wu Suzanna Lewis Ewan Birney Lincoln Stein Molecular Cell Biology Bioinformatics Pathway curation is a powerful tool for systematically associating gene products with functions. Reactome (www.reactome.org) is a manually curated human pathway knowledgebase describing a wide range of biological processes in a computationally accessible manner. The core unit of the Reactome data model is the Reaction, whose instances form a network of biological interactions through entities that are consumed, produced, or act as catalysts. Entities are distinguished by their molecular identities and cellular locations. Set objects allow grouping of related entities. Curation is based on communication between expert authors and staff curators, facilitated by freely available data entry tools. Manually curated data are subjected to quality control and peer review by a second expert. Reactome data are released quarterly. At release time, electronic orthology inference performed on human data produces reaction predictions in 22 species ranging from mouse to bacteria. Cross-references to a large number of publicly available databases are attached, providing multiple entry points into the database. The Reactome Mart allows query submission and data retrieval from Reactome and across other databases. The SkyPainter tool provides visualization and statistical analysis of user supplied data, e.g. from microarray experiments. Reactome data are freely available in a number of data formats (e.g. BioPax, SBML). http://precedings.nature.com/documents/1281/version/1 oai:nature.com:10.1038/npre.2007.1281.1 http://dx.doi.org/10.1038/npre.2007.1281.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1285.1 2007-10-31T20:05:52Z cancer microbiology molecular-cell-biology

Is the infection/latency/reactivation cycle of viruses an oncogenic engine? 2007-10-31T16:53:48Z Alessandro Ripalti Cancer Microbiology Molecular Cell Biology Human oncogenic viruses are defined as necessary but not sufficient to initiate cancer. Experimental evidence suggests that the oncogenic potential of a virus is effective only in cells that have already accumulated a number of genetic mutations leading to cell cycle deregulation. Current models for viral driven oncogenesis cannot explain why tumor development in carriers of tumorigenic viruses is a very rare event, occurring decades after virus infection. Considering that viruses are mutagenic agents _per se_ and human oncogenic viruses additionally establish latent and persistent infections, I attempt here to provide a mechanism of tumor initiation both for RNA and DNA viruses, suggesting viruses could be both necessary and sufficient in human tumorigenesis. I hypothesize a general, albeit inefficient hit and rest mechanism by which viruses may produce a limited reservoir of cells harbouring genetic damage that would be initiated when the virus first hits the cell, before latency is established. Cells surviving genetic damage would consequently become more sensitive to further damage mediated by the otherwise insufficient transforming activity of virus products expressed in latency, or upon episodic reactivations (viral persistence). Cells with a combination of genetic damage leading to a cancerous phenotype would emerge very rarely, as the probability of such an occurrence would be dependent on severity and frequency of consecutive hit and rest cycles due to viral reinfections and reactivations. http://precedings.nature.com/documents/1285/version/1 oai:nature.com:10.1038/npre.2007.1285.1 http://dx.doi.org/10.1038/npre.2007.1285.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1290.1 2007-11-05T16:50:45Z biotechnology neuroscience bioinformatics

An Olfactory Receptor Pseudogene whose Function emerged in Humans 2007-11-02T21:20:16Z Peter Lai Gautam Bahl Maryse Gremigni Valery Matarazzo Olivier Clot-Faybesse Catherine Ronin Chiquito J. Crasto Biotechnology Neuroscience Bioinformatics Human olfactory receptor, hOR17-210, is identified as a pseudogene in the human genome. Experimental data has shown however, that the gene product of cloned hOR17-210 cDNA was able to bind an odorant-binding protein and is narrowly tuned for excitation by cyclic ketones. Supported by experimental results, we used the bioinformatics methods of sequence analysis, computational protein modeling and docking, to show that functionality in this receptor is retained due to sequence-structure features not previously observed in mammalian ORs. This receptor does not possess the first two transmembrane helical domains (of seven typically seen in GPCRs). It however, possesses an additional TM that has not been observed in other human olfactory receptors. By incorporating these novel structural features, we created two putative models for this receptor. We also docked odor ligands that were experimentally shown to bind hOR17-210 model. We show how and why structural modifications of OR17-210 do not hinder this receptor's functionality. Our studies reveal that novel gene rearrangement that result in sequence and structural diversity in has a bearing on OR and GPCR function and evolution. http://precedings.nature.com/documents/1290/version/1 oai:nature.com:10.1038/npre.2007.1290.1 http://dx.doi.org/10.1038/npre.2007.1290.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1291.1 2007-11-07T10:06:51Z neuroscience

What is the function of the C1-C3 adrenergic group in the medulla? 2007-11-02T22:09:26Z John Smythies Neuroscience This brief communication discusses a much neglected topic in functional neuroanatomy-the possible function(s) of the adrenergic system in the brain. http://precedings.nature.com/documents/1291/version/1 oai:nature.com:10101/npre.2007.1291.1 http://hdl.handle.net/10101/npre.2007.1291.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1293.1 2007-11-07T14:48:37Z ecology

IQ variations across time and race are explained by literacy differences 2007-11-03T16:57:33Z David Marks Ecology Intelligence quotient (IQ) scores are intended to assess the cognitive competences of individuals, groups and populations. A body of data collected during the last 50 years has revealed that IQ average population scores vary significantly over time, nationality, and race. The causes of these variations remain a mystery. Theories focusing on nutrition, brain size, dysgenic factors, social class and education have proved inexact or unsatisfactory. Here I describe a new explanation based on the fact that intelligence test performance requires a level of literacy not present in all people to the same degree. I show that literacy variations across time, place and race are highly associated with changes in IQ scores. These findings have widespread implications. Contemporary IQ test score differences between populations and racial groups are predicted to diminish with rises in universal literacy in the 21st century. http://precedings.nature.com/documents/1293/version/1 oai:nature.com:10101/npre.2007.1293.1 http://hdl.handle.net/10101/npre.2007.1293.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1298.1 2007-11-06T21:03:13Z ecology

Bumblebees gain fitness through learning 2007-11-06T17:26:35Z Nigel E. Raine Lars Chittka Ecology Despite the widespread assumption that the learning abilities of animals are adapted to the particular environments in which they operate, the quantitative effects of learning performance on fitness remain virtually unknown. Here we evaluate the learning performance of bumblebees (_Bombus terrestris_) from multiple colonies in an ecologically relevant associative learning task under laboratory conditions, before testing the foraging performance of the same colonies under the field conditions. We demonstrate that variation in learning speed among bumblebee colonies is directly correlated with foraging performance, a robust fitness measure, under natural conditions. Colonies vary in learning speed by a factor of nearly 5, with the slowest learning colonies collecting 40% less nectar than the fastest learning colonies. Such a steep fitness function suggests strong selection for higher learning speed in bumblebees. Demonstrating the adaptive value of differences in learning performance under the real conditions in which animals function represents a major step towards understanding how cognitive abilities of animals are tuned to their environment. http://precedings.nature.com/documents/1298/version/1 oai:nature.com:10101/npre.2007.1298.1 http://hdl.handle.net/10101/npre.2007.1298.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1293.2 2007-11-15T20:37:07Z ecology

IQ variations across time and race are explained by literacy differences 2007-11-08T08:17:24Z David F. Marks Ecology Intelligence quotient (IQ) scores are intended to assess the cognitive competences of individuals, groups and populations. A body of data collected during the last 50 years has revealed that IQ average population scores vary significantly over time, nationality, and race. The causes of these variations remain a mystery. Theories focusing on nutrition, brain size, dysgenic factors, social class and education have proved inexact or unsatisfactory. Here I describe a new explanation based on the fact that intelligence test performance requires a level of literacy not present in all people to the same degree. I show that literacy variations across time, place and race are highly associated with changes in IQ scores. These findings have widespread implications. Contemporary IQ test score differences between populations and racial groups are predicted to diminish with rises in universal literacy in the 21st century. http://precedings.nature.com/documents/1293/version/2 oai:nature.com:10101/npre.2007.1293.2 http://hdl.handle.net/10101/npre.2007.1293.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1299.1 2007-11-14T20:51:10Z biotechnology molecular-cell-biology

Novel Cell type-specific aptamer-siRNA delivery system for HIV-1 therapy 2007-11-08T20:57:32Z Jiehua Zhou Haitang Li Shirley Li John Zaia John Rossi Biotechnology Molecular Cell Biology The successful use of small interfering RNAs (siRNAs) for therapeutic purposes requires safe and efficient delivery to specific cells and tissues. Here we demonstrate cell type-specific delivery of anti-HIV siRNAs via fusion to an anti-gp120 aptamer. The envelope glycoprotein is expressed on the surface of HIV-1 infected cells, allowing binding and interalization of the aptamer-siRNA chimeric molecules. We demonstrate that the anti-gp120 aptamer-siRNA chimera is specifically taken up by cells expressing HIV-1 gp120, and the appended siRNA is processed by Dicer, releasing an anti-tat/rev siRNA which in turn inhibits HIV replication. We show for the first time a dual functioning aptamer-siRNA chimera in which both the aptamer and the siRNA portions have potent anti-HIV activities and that gp120 expressed on the surface of HIV infected cells can be used for aptamer mediated delivery of anti-HIV siRNAs. http://precedings.nature.com/documents/1299/version/1 oai:nature.com:10.1038/npre.2007.1299.1 http://dx.doi.org/10.1038/npre.2007.1299.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1306.1 2007-11-12T20:22:44Z neuroscience

A new approach to the spatio-temporal pattern identification in neuronal multi-electrode registrations 2007-11-09T19:17:37Z Federico Esposti Jacopo Lamanna Maria Gabriella Signorini Neuroscience A lot of methods were created in last decade for the spatio-temporal analysis of multi-electrode array (MEA) neuronal data sets. All these methods were implemented starting from a channel to channel analysis, with a great computational effort and onerous spatial pattern recognition task. 
Our idea is to approach the MEA data collection from a different point of view, i.e. considering all channels simultaneously. We transform the 2D plus time MEA signal in a mono-dimensional plus time signal and elaborate it as a normal 1D signal, using the Space-Amplitude Transform method. 
This geometrical transformation is completely invertible and allows to employ very fast processing algorithms. 
 http://precedings.nature.com/documents/1306/version/1 oai:nature.com:10.1038/npre.2007.1306.1 http://dx.doi.org/10.1038/npre.2007.1306.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1309.1 2007-11-10T16:18:40Z molecular-cell-biology

Novel role of substance-p as a systemic wound messenger to mobilize mesenchymal stem cell from bone marrow and be engaged in the wound healing epithelial layer 2007-11-10T10:44:17Z Hyun Sook Hong Jung Sun Lee Young Sam Kwon Eun Kyung Lee Woosung Ahn Jae Chan Kim Youngsook Son Molecular Cell Biology Tissue injury may bring up the systemic participation of bone marrow stem cells in the repair. In this study, we report that substance-p is a systemically acting messenger to mobilize mesenchymal stem cell (MSC) probably from the bone marrow and be engaged in the wound healing process. This was supported by the injury-inducible substance-p detection in the tissue and the peripheral blood and subsequent MSC mobilization in the alkali-burn rabbit eye model, whose kinetics were dependent on the wound size. Furthermore, i.v. injection of exogenous substance-p stimulated MSC mobilization in the uninjured rabbits and those mobilized cells showed multipotent differentiation capacity. We demonstrated that earlier substance-p elevation in the circulation by substance-p injection or transfusion of autologous PKH-labeled MSC mobilized by substance-p strongly accelerated the wound healing of the alkali-burned rabbit eye and the transfused MSCs were engrafted to the epithelial and stromal layer of the injured tissue, suggesting their epithelial transdifferentiation in the regenerating tissue. Finally, we showed that substance-p stimulated transmigration of human MSC with concomitant induction of MMPs and inhibition of their inhibitors, cell proliferation, ERK1/2 activation, and nuclear translocation of [beta]-catenin _in vitro_. In conclusion, substance-p plays a role as a systemic wound-messenger to promote the MSC mobilization from the marrow and their participation in the wound healing possibly through its stimulant effect on MSC repopulation as well. http://precedings.nature.com/documents/1309/version/1 oai:nature.com:10101/npre.2007.1309.1 http://hdl.handle.net/10101/npre.2007.1309.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1260.3 2007-11-14T10:59:23Z neuroscience

Reciprocal homeostatic reactions to chronic excitatory synaptic receptor inactivation in developing cerebral cortex networks 2007-11-11T10:36:56Z Michael A. Corner Neuroscience Chronic blockade of actively excitatory glutamatergic synaptic receptors in co-cultured organotypic rodent neocortex explants leads to a compensatory up-regulation of otherwise inactive input channels so as to maintain almost normal levels of ongoing bursts of action potentials. We report here that this homeostatic return of spontaneous (now kainate receptor driven) firing is accompanied by a reciprocal down-regulation of blocked AMPA and NMDA receptors, such that the developing cortical network is protected against becoming hyperactive when those synaptic inputs are again able to transmit normally. http://precedings.nature.com/documents/1260/version/3 oai:nature.com:10.1038/npre.2007.1260.3 http://dx.doi.org/10.1038/npre.2007.1260.3 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.932.2 2007-11-12T16:40:59Z genetics evolutionary-biology

Telomeres in Evolution and Development from Biosemiotic Perspective 2007-11-11T17:47:49Z Guenther Witzany Genetics & Genomics Evolutionary Biology Whereas telomeres protect terminal ends of linear chromosomes, telomerases identify natural chromosome ends being different from broken DNA. Although telomeres play a crucial role in the linear chromosome organisation of eukaryotic cells, their molecular syntax descended from an ancient retroviral competence. This is an indicator for the early retroviral colonization of large double stranded DNA viruses, which are putative ancestors of the eukaryotic nucleus.

This contribution will demonstrate an advantage of the biosemiotic approach towards our evolutionary understanding of telomeres: focus on the genetic/genomic structures as language-like text which follows combinatorial (syntactic), context-sensitive (pragmatic) and content-specific (semantic) semiotic rules. Genetic/genomic organisation from the biosemiotic perspective is not seen any longer as an object of randomly derived alterations (mutations) but as functional innovation coherent with the broad variety of natural genome editing competences of viruses. http://precedings.nature.com/documents/932/version/2 oai:nature.com:10.1038/npre.2007.932.2 http://dx.doi.org/10.1038/npre.2007.932.2 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1311.1 2007-11-12T16:51:55Z cancer molecular-cell-biology bioinformatics

The NCI-Nature Pathway Interaction Database: A cell signaling resource. 2007-11-12T16:17:58Z Shiva Krupa Kira Anthony Jeffrey R. Buchoff Matthew Day Timo Hannay Carl F. Schaefer Cancer Molecular Cell Biology Bioinformatics The Pathway Interaction Database (*PID*, http://pid.nci.nih.gov) is a freely available
collection of curated and peer-reviewed signaling pathways composed of human
biomolecular interactions and cellular processes. Created in a collaboration between the
U.S. National Cancer Institute and Nature Publishing Group, the database is a research
tool for cell biologists, biochemists, computational biologists and bioinformaticians.
The PID offers a range of tools to facilitate pathway exploration. Users can browse the
pre-defi ned set of pathways and also create interaction network maps centered on
a single molecule of interest or an extensive list of molecules. In addition, users can
download complete data sets in extensible markup language (XML) and Biological
Pathway Exchange (BioPAX) Level 2 formats. The database is updated every month and
supplemented by a concise editorial section that provides synopses of recent noteworthy
papers in cell signaling and specially commissioned articles on the practical uses of
other relevant online tools. Users can sign up for free email alerts or RSS feeds to receive
database updates. http://precedings.nature.com/documents/1311/version/1 oai:nature.com:10.1038/npre.2007.1311.1 http://dx.doi.org/10.1038/npre.2007.1311.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1312.1 2007-11-12T21:53:05Z biotechnology chemistry

Photoelectrochemical properties of melanin 2007-11-12T17:34:40Z Arturo Solis Maria E. Lara Luis E. Rendon Biotechnology Chemistry Melanin is to the animal kingdom like chlorophyll to the vegetal kingdom(1). Melanin collects energy from lower-energy radiation sources, kicks electrons into excited states, initiating a process that would end up producing chemical energy, similar to the way in which photosynthesis supplies energy to plants. However, the precise roles of melanin during this process are unknown. Here we show that the increase in the electron-transfer properties of melanin is independent of the energy of the incident photons. We found in controlled in vivo assays that melanin has the remarkable capability of converting lower-energy radiation towards a more useful form of energy. Furthermore, we found that melanin can break up water molecules and giving up energy suggesting an additional behavior mode for melanin. Our results demonstrate how members of the melanin family are likely to function as transducers, oxidizing water, pushing apart water molecules, as well as recruiting back ions into molecules that are subsequently polarized again. Melanin drives the photon energy of lower-energy radiation sources by quenching electrons and initiating an ionic event independently of their relative energy contention. We anticipate our assay to be a starting point for more sophisticated photoelectrochemical applications. For example, the individual and combined action of multiple photovoltaic applications could be tested, including conducting polymers, for example poly-(phenylenevinylene) (PPV) derivatives or C60 particles. Furthermore, melanin's energy conversion ability is a major target of solar energy conversion development, and an organic-semiconductor way for photoelectrochemical applications will be relevant for such developments.</sup></sup> http://precedings.nature.com/documents/1312/version/1 oai:nature.com:10101/npre.2007.1312.1 http://hdl.handle.net/10101/npre.2007.1312.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1313.1 2007-11-13T21:17:22Z earth-and-environment

A Case For Killing Humpback Whales? 2007-11-12T23:12:47Z Nicholas J. Gales Phillip J. Clapham C. Scott Baker Earth & Environment During the austral summer of 2007/08, hunting of Southern Hemisphere (SH) humpback whales will recommence after almost half a century of protection. The stated rationale for this hunt, by the Government of Japan (GoJ), is to gather important scientific information for use in management. If the scientific need were defensible, and the proponents had accommodated reasonable conservation concerns, then criticisms of the hunt would be limited to philosophical issues. This is not the case. The program’s research objectives are unlikely to be achieved by lethal methods and do not address the principal research needs for SH humpback whales identified by the International Whaling Commission (IWC). http://precedings.nature.com/documents/1313/version/1 oai:nature.com:10101/npre.2007.1313.1 http://hdl.handle.net/10101/npre.2007.1313.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1314.1 2007-11-13T22:44:16Z cancer

Method of Detecting and Targeting Mutations in Cancer 2007-11-13T22:02:52Z Byard Edwards Cancer While there are many differences between tumor and non-tumor cells, the basic underlying distinction is in the DNA. Tumor cells harbor mutations, at least some of which are not present in non-tumor cells. Thus, a method of directly targeting cells containing specific mutations has potential for detection or treatment of cancer without the toxicity associated with more indirect approaches. Also, as mutations are a necessary component of malignancy, such a method is potentially applicable to all tumors. 

I propose a method by which several recently developed techniques can be utilized in a novel way to accomplish the goal of directly targeting mutations for cancer detection and therapy. The model can be summarized as follows: (1) Determine potential target mutations present in tumor cells but not non-tumor cells. (2) Construct molecules that will bind to DNA at the sites of mutation, but will not bind to DNA in normal cells. And, as a consequence of the molecules binding to the mutation, the cells will be destroyed. (3) Deliver these molecules to all cells (or at least all tumor cells). I hypothesize that such molecules can now be constructed using sequence-specific DNA binding proteins (such as customized zinc-finger DNA binding proteins) fused to transcriptional activator domains (such as VP16) and reporter or toxin genes. The necessary genes can be linked to the DNA binding proteins utilizing a recently described method based on expressed protein ligation. 
 http://precedings.nature.com/documents/1314/version/1 oai:nature.com:10.1038/npre.2007.1314.1 http://dx.doi.org/10.1038/npre.2007.1314.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1317.1 2007-11-14T15:53:40Z molecular-cell-biology bioinformatics

Creatine kinase in energy metabolic signaling in muscle 2007-11-14T14:44:25Z Olav Kongas Johannes H. G. M. van Beek Molecular Cell Biology Bioinformatics There has been much debate on the mechanism of regulation of mitochondrial ATP synthesis to balance ATP consumption during changing cardiac workloads. A key role of creatine kinase (CK) isoenzymes in this regulation of oxidative phosphorylation and in intracellular energy transport had been proposed, but has in the mean time been disputed for many years. It was hypothesized that high-energy phosphoryl groups are obligatorily transferred via CK; this is termed the phosphocreatine shuttle. The other important role ascribed to the CK system is its ability to buffer ADP concentration in cytosol near sites of ATP hydrolysis. 

Almost all of the experiments to determine the role of CK had been done in the steady state, but recently the dynamic response of oxidative phosphorylation to quick changes in
cytosolic ATP hydrolysis has been assessed at various levels of inhibition of CK. Steady state models of CK function in energy transfer existed but were unable to explain the dynamic response with CK inhibited.

The aim of this study was to explain the mode of functioning of the CK system in heart, and in particular the role of different CK isoenzymes in the dynamic response to workload steps. For this purpose we used a mathematical model of cardiac muscle cell energy metabolism containing the kinetics of the key processes of energy production, consumption and transfer pathways. The model underscores that CK plays indeed a dual role in the cardiac cells. The buffering role of CK system is due to the activity of myofibrillar CK (MMCK) while the energy transfer role depends on the activity of mitochondrial CK (MiCK). We propose that this may lead to the differences in regulation mechanisms and energy transfer modes in species with relatively low MiCK activity such as rabbit in comparison with species with high MiCK activity such as rat.

The model needed modification to explain the new type of experimental data on the dynamic response of the mitochondria. We submit that building a Virtual Muscle Cell is not possible without continuous experimental tests to improve the model. In close interaction with experiments we are developing a model for muscle energy metabolism and transport mediated by the creatine kinase isoforms which now already can explain many different types of experiments. http://precedings.nature.com/documents/1317/version/1 oai:nature.com:10.1038/npre.2007.1317.1 http://dx.doi.org/10.1038/npre.2007.1317.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1320.1 2007-11-15T14:06:48Z ecology evolutionary-biology

The Earliest Perfect Flower 2007-11-15T02:54:50Z Xin Wang Shaolin Zheng Ecology Evolutionary Biology Despite of angiosperms in the Yixian Formation (>125 Ma, early Cretaceous), there is no perfect flower typical of angiosperms to date. Here we report _Euanthus dilaensis_ gen. et sp. nov as the earliest perfect flower known to date. The flower includes tepals, androecium and gynoecium. The anthers are globose in form, with bristles atop and in situ round-triangular pollen grains. The gynoecium is composed of probably two carpels with plumose stigmas and a carpel-enclosing receptacle. The discovery of _Euanthus_ increases the diversity of early angiosperms, and indicates that perfect flowers occurred as early as 125 Ma ago.
 http://precedings.nature.com/documents/1320/version/1 oai:nature.com:10101/npre.2007.1320.1 http://hdl.handle.net/10101/npre.2007.1320.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1321.1 2007-11-15T19:50:52Z neuroscience

Body-specific representations of action word meanings in right and left handers 2007-11-15T10:23:15Z Daniel Casasanto Neuroscience If understanding action words involves mentally simulating our own actions, then the neurocognitive representation of word meanings must differ for people with different kinds of bodies, who perform actions in systematically different ways. In a test of the _Body-Specificity Hypothesis_, right- and left-handers were compared on two motor-meaning congruity tasks. Double dissociations in both action execution and recognition memory results showed that right and left handers form body-specific representations of words for manual actions. http://precedings.nature.com/documents/1321/version/1 oai:nature.com:10101/npre.2007.1321.1 http://hdl.handle.net/10101/npre.2007.1321.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1324.1 2007-11-16T16:44:38Z ecology

Ecological optimum of ectothermic organisms: static-dynamical approach 2007-11-15T15:17:33Z Vladimir V. B. Verbitsky Tamara T. I. Verbitskaya Ecology During 20th century the majority of researchers interpreted ecological optimum as a certain combination of ambient factors which is optimal for growth, existence and reproduction of an organism. However, it was revealed in many species, that the maximum rates of various processes in an organism are achieved at various combinations of values of different factors, and under variable regimes as opposite to constant regimes. One may state that there is no well defined general concept which takes into account a bulk of data that do not conform the traditional definition of ecological optimum. Here, we show that it is necessary to make distinction between concepts of "static" and "dynamic" optima. It is needed for definition of real ecological optimum and creation of optimum conditions for given factor. We show also that it is necessary to take into account so-called delayed effects of factors. Basing on the analysis of responses of zooplankton to various temperatures and phosphoric load, we show that an optimum has "dynamic" characteristics besides previously known "static" ones, like a range of factor values on tolerance curve or a doze of factor. These "dynamic" characteristics are cyclic and stepwise changes of a factor, a directionality of factor's dynamics in case of stepwise changes and additionally, we reveal stimulating and inhibiting delayed effects of factors. Our results allow for a more detailed concept of ecological optimum, and also may stimulate investigations of quantitative contribution of various parameters of environmental factors to an ecological optimum of an organism or population. http://precedings.nature.com/documents/1324/version/1 oai:nature.com:10101/npre.2007.1324.1 http://hdl.handle.net/10101/npre.2007.1324.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1328.1 2007-11-15T22:31:08Z neuroscience

Correlation between Pineal Activation and Religious Meditation Observed by Functional Magnetic Resonance Imaging 2007-11-15T17:24:20Z Chien-Hui Liou Chang-Wei Hsieh Chao-Hsien Hsieh Si-Chen Lee Jyh-Horng Chen Chi-Hong Wang Neuroscience The human brain possesses plenty of functions but little is known about its scientific relationship with mind and spirit. Conferences^1,2^ focused on the connection between science and religion were held very recently in which neuroscientists, Buddhist scholars and Dalai Lama discussed attention, mental imagery, emotion, mind, brain functions and meditation, suggesting religious meditation offers an effective means to investigate the mystery of mind and spirit. In the past decade, scientists struggled to obtain brain mappings for various meditation styles using different brain imaging techniques and stimulating results have been observed^3-17^. In this letter we report that, together with other brain regions, pineal body exhibit significant activation during meditation process, supporting the long lasting speculation that pineal plays an important role in the intrinsic awareness which might concern spirit or soul. Pineal is known as an endocrine organ which produces substrates including melatonin and has been ascribed numerous even mysterious functions but its activation during meditation has never been observed by brain imaging technique. In seventeenth century, based on anatomic observation, Descartes ventured to suggest that pineal serves as the principal seat of the soul^18-20^. Inspired by its geometric center in the brain, physiologists, psychologists, philosophers and religionists have been speculating for centuries about pineal's function relevant to spirit and soul. In this study, we chose Chinese Original Quiet Sitting, one style of meditation, to explore this long lasting speculation by functional magnetic resonance imaging technique. Our results demonstrate a correlation between pineal activation and religious meditation which might have profound implications in physiological understanding of the intrinsic awareness. http://precedings.nature.com/documents/1328/version/1 oai:nature.com:10101/npre.2007.1328.1 http://hdl.handle.net/10101/npre.2007.1328.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1347.1 2007-11-19T17:02:49Z biotechnology microbiology molecular-cell-biology plant-biology

Reversal of an immunity associated plant cell death program by the growth regulator auxin 2007-11-18T18:01:56Z Suresh Gopalan Biotechnology Microbiology Molecular Cell Biology Plant Biology One form of plant immunity against pathogens involves a rapid host programmed cell death at the site of infection accompanied by resistance, termed the hypersensitive response (HR). Here it is shown that the HR programmed cell death program initiated by the bacterial type III secretion system dependent proteinaceous elicitor harpin from Erwinia amylovora can be reversed till very late in the process by the plant growth regulator auxin. Early inhibition or late reversal of this cell death program does not affect marker genes tightly correlated with local and systemic resistance. Cross-regulation between cell death programs and growth regulators is prevalent in different kingdoms. Thus, the concept that cell death program can be reversed till late provides a framework for further investigation of such phenomena, in addition to having utility in choosing better targets and strategies for treating mammalian and agricultural diseases. http://precedings.nature.com/documents/1347/version/1 oai:nature.com:10.1038/npre.2007.1347.1 http://dx.doi.org/10.1038/npre.2007.1347.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1351.1 2007-11-19T16:11:41Z ecology

Bioluminescence emission of the firefly 2007-11-19T10:12:59Z Anurup Gohain Barua Simanta Hazarika Nayanmoni Saikia Gaurangadhar Baruah Ecology We have recorded _in vivo_ emission and time-resolved spectra of the firefly species _Pyrophorus noctilucus_. The emission spectrum shows the FWHM value for this particular species to be 55 nm, which is significantly smaller than the half widths reported till now. The time-resolved spectrum reveals that a flash, of duration about a hundred milliseconds, is in fact composed of a number of microsecond pulses. This result suggests that the speed of the enzyme-catalyzed chemiluminescence reaction in the firefly for the emission of light is much greater than is believed to be. http://precedings.nature.com/documents/1351/version/1 oai:nature.com:10101/npre.2007.1351.1 http://hdl.handle.net/10101/npre.2007.1351.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1352.1 2007-11-19T20:14:15Z biotechnology

Cryopreservation of a whole liver 2007-11-19T15:16:49Z Zohar Gavish Amir Arav Menahem Ben-Haim Biotechnology Preservation of vascularized organs such as the liver is limited to 24hrs. before destructive processes disqualify it for transplantation. This narrow time window prevents surgeons from performing optimal pathogen screening and matching tests which often lead to re-transplantation. Numerous problems are associated with viably freezing and thawing a whole liver: complicated geometry, poor heat transfer, release of latent heat and the difficulty of generating a uniform cooling rate. Our past success led us to apply our novel freezing technique to a larger solid organ, the liver. Whole livers were frozen/thawed using a directional solidification apparatuses; viability was tested by means of integrity and functionality in vitro and in auxiliary liver transplantation. Thawed livers were intact with over 80% viability; histology revealed normal architecture, bile production and blood flow following auxillary transplantation where normal. Our results suggest a novel cryopreservation method and may enable better organ donor-recipient matching in the future http://precedings.nature.com/documents/1352/version/1 oai:nature.com:10101/npre.2007.1352.1 http://hdl.handle.net/10101/npre.2007.1352.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1353.1 2007-11-20T12:32:03Z neuroscience

A visual sense of number 2007-11-20T08:56:35Z David Burr John Ross Neuroscience Evidence exists for a non-verbal capacity to apprehend number, in humans^1^ (including infants^2,3^) and in other primates^4-6^. Here we show that perceived numerosity is susceptible to adaptation, along with primary visual properties of a scene like colour, contrast, size and speed. Apparent numerosity was decreased by adapting to large numbers of dots and increased by adapting to small numbers, the effect depended entirely on the numerosity of the adapter, not on contrast, size, orientation or pixel density, and occurred with very low adapter contrasts. We suggest that numerosity is also an independent primary visual property, not reducible to others like spatial frequency or density of texture^7^. http://precedings.nature.com/documents/1353/version/1 oai:nature.com:10101/npre.2007.1353.1 http://hdl.handle.net/10101/npre.2007.1353.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1354.1 2007-11-20T18:16:18Z genetics neuroscience

Dissecting the mechanisms of learning-by-doing in Drosophila 2007-11-20T17:04:04Z Björn Brembs Wolfgang Plendl Genetics & Genomics Neuroscience At the heart of learning-by-doing lies a well-known psychological phenomenon: information will be remembered better if it is actively generated rather than passively read or heard. First described in humans, this generation effect can also be observed in various animal models. However, the neurobiological mechanisms underlying the generation effect are unknown. Here we show that two reciprocal interactions between its active and passive components contribute to the generation effect in flies. One interaction consists of the active (skill-learning) component facilitating the passive (fact-learning) component. Fact-learning, on the other hand, inhibits skill-learning. Experiments with adenylyl cyclase I deficient _rutabaga_ mutant flies revealed that the fact- but not the skill-learning component requires this evolutionarily conserved learning gene. Using mushroom-body deficient transgenic flies we observed that the mushroom-bodies mediate the inhibition of skill-learning. This inhibition also enables generalization and prevents premature habit formation. Extended training in wildtype flies produced a phenocopy of mushroom-body impaired flies, such that generalization was abolished and goal-directed actions were transformed into habitual responses. Thus, our results identify various neural processes underlying learning-by-doing, delineate some of their synergisms and provide a framework for further dissecting them in a genetically tractable model system. http://precedings.nature.com/documents/1354/version/1 oai:nature.com:10101/npre.2007.1354.1 http://hdl.handle.net/10101/npre.2007.1354.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1356.1 2007-11-20T23:00:17Z ecology neuroscience

Vocal Bursts Communicate Discrete Emotions: Evidence for New Displays 2007-11-20T19:46:26Z Emiliana Simon-Thomas Disa Sauter Lara Sinicropi-Yao Anna Abramson Dacher Keltner Ecology Neuroscience Studies of emotion signaling have proven critical to scientific advances in understanding emotion, informing claims about the evolutionary origins of different emotions1, the central and peripheral nervous system correlates of emotion 2 3 and even which states warrant consideration in emotion taxonomies 4. An initial wave of empirical studies of emotion-related facial expression5 and vocalization 6 7 has concentrated almost exclusively on a limited set of emotions - anger, disgust, fear, sadness, surprise, happiness, and tenderness. More recent work on emotional facial expressions has expanded this framework, documenting reliable displays of other emotions like embarrassment and shame 8, pride 9, and love and desire 10 . Here, we present two studies that evaluate the voice's ability to communicate 22 different emotions, including positive emotions like awe, love and sensory pleasure as well as self-conscious emotions like embarassment and guilt. These studies show that vocal bursts signal a greater number of discrete emotions than has been previously documented and that some emotions are better identified within families of related emotions. http://precedings.nature.com/documents/1356/version/1 oai:nature.com:10101/npre.2007.1356.1 http://hdl.handle.net/10101/npre.2007.1356.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1359.1 2007-11-27T10:20:21Z earth-and-environment

Cartographic scale effect on channel slopes and stream power calculations 2007-11-22T18:08:11Z Adalto Gonçalves Lima Earth & Environment The channel slope is important in determining the stream power. In some research situations the slope is measured by topographical maps that, depending on the scale, can provide differentiated values. The objective of the research here reported was to delineate the implications of the inter-scales differences of channel slopes on the stream power calculation. Slopes of a small river, with a mixed bedrock–alluvial bed, located in a basaltic plateau in south Brazil, were examined. The measured slopes were compared at 1:50,000 and 1:10,000 scales. In the field, the bankfull geometry was surveyed in ten cross sections, for discharge calculation. The slopes measured by maps were used to determine the discharge, using the Gauckler–Manning equation, and to calculate the total and specific stream power. A tendency was verified for the 1:50,000 scale to overestimate the values in reaches of low slopes (<0.05), coinciding with mixed bedrock–alluvial reaches, while it underestimates in the reaches of larger slopes, i.e. knickzones. As larger is the absolute difference of slope between the analyzed scales, the larger is the stream power differential (%), and as smaller the slopes involved the larger will be that differential. In the analysed case, total and specific stream power differentials vary from 14.6 to 313.4%. http://precedings.nature.com/documents/1359/version/1 oai:nature.com:10101/npre.2007.1359.1 http://hdl.handle.net/10101/npre.2007.1359.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1363.1 2007-11-26T15:22:29Z biotechnology

The study on estimation of time since death with proton magnetic resonance spectroscopy under different temperature 2007-11-26T10:50:14Z Tiantong Yang Li Zhenwei Wu Yue Liu Liang Zheng Na Biotechnology Estimation of the time of death (post-mortem interval, PMI) is occasionally a critical issue in adjudication of a criminal or civil action. But no objective and precise means has been derived for estimating PMI.One reason for this outcome may be the fact that most of these methods attempted to characterize PMI by a few or even just one specific parameter's variable in constant ambient temperature. It is crucial that we reduce or eliminate the effect of temperature variation in the estimation of PMI. Here we show the first results by using proton magnetic resonance spectroscopy (1H-MRS) technique to determine the order of degradation of certain substances, present in the brain tissue of a rabbit model, under different temperatures; our goal is to reduce or eliminate the temperature effect in the estimation of PMI. http://precedings.nature.com/documents/1363/version/1 oai:nature.com:10101/npre.2007.1363.1 http://hdl.handle.net/10101/npre.2007.1363.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1364.1 2007-11-28T12:06:18Z cancer genetics bioinformatics

ChIP-on-chip significance analysis reveals large-scale binding and regulation by human transcription factor oncogenes 2007-11-26T20:49:14Z Adam A. Margolin Teresa Palomero Pavel Sumazin Andrea Califano Adolfo Ferrando Gustavo A. Stolovitzky Cancer Genetics & Genomics Bioinformatics ChIP-on-chip has emerged as a powerful tool to dissect the complex network of regulatory interactions between transcription factors and their targets. However, most ChIP-on-chip analysis methods use conservative approaches aimed to minimize false-positive transcription factor targets. We present a model with improved sensitivity in detecting binding events from ChIP-on-chip data. Biochemically validated analysis in human T-cells reveals that three transcription factor oncogenes, NOTCH1, MYC, and HES1, bind one order of magnitude more promoters than previously thought. Gene expression profiling upon NOTCH1 inhibition shows broad-scale functional regulation across the entire range of predicted target genes, establishing a closer link between occupancy and regulation. Finally, the resolution of a more complete map of transcriptional targets reveals that MYC binds nearly all promoters bound by NOTCH1. Overall, these results suggest an unappreciated complexity of transcriptional regulatory networks and highlight the fundamental importance of genome-scale analysis to represent transcriptional programs. http://precedings.nature.com/documents/1364/version/1 oai:nature.com:10101/npre.2007.1364.1 http://hdl.handle.net/10101/npre.2007.1364.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1368.1 2007-12-03T10:58:56Z chemistry pharmacology

Prehistoric psychotropic consumption in Andean Chilean mummies 2007-11-29T00:18:42Z Juan P. Ogalde Bernardo T. Arriaza Elia Soto Chemistry Pharmacology Hallucinogenic plants are often regarded as the main source of psychoactive drugs in antiquity to reach deep altered states of consciousness^1,2^. Many researchers believe this was particularly true during the Tiwanaku empire expansion, circa (500-1000 A.D.), along the Atacama Desert of Chile. Highly decorated snuffing tablets and tubes are often found as grave goods during this period^3,4,5,6,7,8^. Until now the type of drugs consumed in this paraphernalia has been unclear. From the modern city of Arica, naturally mummified human bodies with abundant hair provided a unique opportunity to test for hallucinogenic plants consumed in Andean prehistory. Analysis by gas chromatography and mass spectrometry demonstrated the presence of harmine. The Banisteriopsis vine, commonly called Ayahuasca, was the probable source. This is the first confirmed evidence of psychoactive plant consumption in pre-Hispanic Andean populations along the Atacama coastal region. Of the 32 mummy hair samples analyzed 3 males tested positive for harmine. This alkaloid aids in the catalysis and synergic effects of powerful hallucinogenic drugs. The consumption of harmine was likely related to medicinal practices and not exclusively ingested by shamans. Another important aspect of this evidence is that Banisteriopsis is an Amazon plant. It does not grow in the Atacama coastal region. Thus, our findings reveal extensive plant trade networks in antiquity between the coast, desert, highlands, and Amazon basin. The excellent preservation of human organic specimens, the use of gas chromatography and mass spectrometry allowed us to map and demonstrate the consumption of psychoactive compound plants in Andean prehistory. In addition, our findings open the door for future studies to debate the consumption and social role of ancient psychoactive and hallucinogenic plants. http://precedings.nature.com/documents/1368/version/1 oai:nature.com:10101/npre.2007.1368.1 http://hdl.handle.net/10101/npre.2007.1368.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1370.1 2007-12-10T16:51:06Z biotechnology chemistry genetics molecular-cell-biology bioinformatics

The Open Practises E-Science Network (OPEN) 2007-11-29T15:11:05Z Cameron Neylon Biotechnology Chemistry Genetics & Genomics Molecular Cell Biology Bioinformatics A grant proposal submitted for support to fund a research network focussed on identifying and dealing with the practical issues of enabling open practise in research. The text of the proposal was written by a large number of people and coordinated by Cameron Neylon. http://precedings.nature.com/documents/1370/version/1 oai:nature.com:10.1038/npre.2007.1370.1 http://dx.doi.org/10.1038/npre.2007.1370.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1371.1 2007-11-29T22:01:54Z earth-and-environment

Multidimensional structure of stream flow regime in a hierarchy of landscapes within the U.S. Great Lakes basin 2007-11-29T21:01:31Z Boris Shmagin Carol Johnston Scott Bridgham Earth & Environment Stream flow data were used to evaluate a landscape hierarchy ranging from the Ontonagon River watershed (OW) to the upper peninsula of Michigan (MUP) to the entire Great Lakes basin (GLB). Flow records (1926-1988) were obtained for 45 USGS gauging stations within the GLB with drainage areas of 100-1450 sq. mi. Data were arranged in five initial matrixes with number of time series from 14 to 45. Factor analysis of average annual flow revealed from three to six patterns of stream runoff within distinct regions of the GLB. A typical watershed was selected to represent each of the five distinct regions identified for the period 1956-88, and its data were used to analyze monthly average flow values. This analysis identified two to five groupings of months with similar flow characteristics. For each annual time series of the typical five stream flow patterns of GLB regression equations were obtained from fore main indices of global atmospheric circulation. A similar analysis was completed for MUP and OW. Multilevel and multidimensional time spatial structure was discovered with factor as axis within landscape units as a homogeneous field. This kind of structure allows direct and more precise research for similar structures in atmosphere circulation and atmosphere-hydrosphere connections and regimes for entire GLB and its parts. http://precedings.nature.com/documents/1371/version/1 oai:nature.com:10.1038/npre.2007.1371.1 http://dx.doi.org/10.1038/npre.2007.1371.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1373.1 2007-11-30T18:29:36Z ecology

The transmission dynamics of syphilis and the CDC’s elimination plan 2007-11-29T23:14:29Z Romulus Breban Virginie Supervie Justin Okano Raffaele Vardavas Sally Blower Ecology The Centers for Disease Control (CDC) is currently attempting to eliminate syphilis in the United States (US); to ensure that their control strategies will be effective it is important to understand the transmission dynamics of syphilis. Epidemics of certain infectious diseases (e.g., influenza) can rise and fall with a well-defined periodicity; this cycling behavior is important because it can have significant implications for the design and effectiveness of control strategies. Here we discuss the methodology that has been used to identify epidemic cycles in longitudinal data sets, and the endogenous and exogenous mechanisms that generate cycling. We then examine the recently proposed hypothesis that syphilis epidemics cycle. This hypothesis was proposed based upon the results of a spectral analysis of a longitudinal data set that had been collected by the (CDC), and the analysis of a syphilis transmission model. We use spectral analysis to reanalyze the CDC’s data set, as well as to analyze a longitudinal mortality data set provided by the CDC. We also use published transmission models to predict the expected dynamics of syphilis epidemics. In contrast to the previous findings we find that: (i) that neither of the CDC’s data sets provide compelling evidence that syphilis epidemics cycle and (ii) published transmission models predict that syphilis epidemics should monotonically decrease (as a function of the treatment rate) rather than cycle. We explain the reasons why previous authors had proposed that syphilis epidemics cycle. Finally, we discuss the implications of our findings regarding the transmission dynamics of syphilis for the CDC’s elimination plan. http://precedings.nature.com/documents/1373/version/1 oai:nature.com:10.1038/npre.2007.1373.1 http://dx.doi.org/10.1038/npre.2007.1373.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1375.1 2007-11-30T22:36:43Z evolutionary-biology

To every man his own language: Are we all Darwin’s children? 2007-11-30T14:18:50Z Shantanu Ghosh Evolutionary Biology Although current theories of language evolution have examined both molecular evolution as well as functional connectivity of the cortex in humans as well as other primates, a description of language as pre-adaptation open to natural selection has eluded us so far. Here I review the evidence in favor of natural selection that trigger growth and plasticity of the prefrontal cortex in humans and its links to the mirror neuron system. Evolvability of recursive mechanisms as the hallmark of evolution of symbolic communication in humans is also investigated. The polymorphism of genes like ASPM, Microcephalin and FOXP2 in the evolution of language as an emergent property has also been examined. http://precedings.nature.com/documents/1375/version/1 oai:nature.com:10101/npre.2007.1375.1 http://hdl.handle.net/10101/npre.2007.1375.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1376.1 2007-11-30T21:30:43Z ecology genetics bioinformatics

Evolution of the Protein Universe. Time Scales and Selection 2007-11-30T15:36:15Z Marco Cosentino Lagomarsino Alessandro Sellerio Philip Heijning Bruno Bassetti Ecology Genetics & Genomics Bioinformatics The availability of many genome sequences gives us abundant information, which is, however, very difficult to decode. As a consequence, in order to advance our understanding of biological processes at the whole-cell scale, it becomes very important to develop higher-level, synthetic descriptions of the contents of a genome. At the protein level, an effective scale of description is provided by protein domains. Domains are independent unit-shapes (or "folds") forming proteins. They are structurally stable and have thermodynamic origin. A domain determines a set of potential functions and interactions for the protein that carries it, for example DNA- or protein-binding capability or catalytic sites. Protein domains are found on genomes with notable statistical distributions, which bear a high degree of similarity. A stochastic growth model with two universal parameters, related to a minimal number of domains and to the relative time-scale of innovation to duplication reproduces two important features of these distributions: (i) the populations of domain classes (the sets, related to homology classes, containing realizations of the same domain in different proteins) follow common power-laws whose diversity is related to genome size measured by the total number of proteins or protein domains and (ii) the number of domain families is sublinear in genome size. In this evolutionary process, selective pressure can enter both as a global constraint on the innovation time-scale, and as a regulator of the population of specific domain classes, related to their modularity: some shapes are common to all genomes, some are contextual. These two features are sufficient to obtain general quantitative agreement with data from hundreds of genomes, and show that robust self-organizing phenomena encase specific selective pressures during evolution. http://precedings.nature.com/documents/1376/version/1 oai:nature.com:10101/npre.2007.1376.1 http://hdl.handle.net/10101/npre.2007.1376.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1381.1 2007-12-17T12:02:37Z microbiology molecular-cell-biology

Water and the Biology of Prions and Plaques 2007-12-01T11:53:28Z Graham K. Steel Phillippa M. Wiggins Microbiology Molecular Cell Biology This is an attempt to account for the insolubility and/or aggregation of prions and plaques in terms of a model of water consisting of an equilibrium between high 
density and low density microdomains. Hydrophobic molecules, including proteins, 
accumulate selectively into stable populations, enriched in high density water, at 
charged sites on biopolymers. In enriched high density water, proteins are probably 
partially unfolded and may precipitate out when released. All extracellular matrices 
contain such charged polymers. Prions, which have been shown to accumulate in soils 
and clays containing silicates and aluminates also probably accumulate in 
extracellular matrices. 
 
Release of proteins follows hydrolysis of the charged groups by highly reactive high 
density water. This is normally a slow process but is greatly accelerated by urea. 
Plaques may form with age and disease because of accumulation of urea and, perhaps, 
glucose in the blood. This favours precipitation of proteins emerging from matrices, 
rather than refolding and solution. Dialysis should, therefore, interfere with plaque 
formation and impede the development of some age-related diseases. http://precedings.nature.com/documents/1381/version/1 oai:nature.com:10101/npre.2007.1381.1 http://hdl.handle.net/10101/npre.2007.1381.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1382.1 2007-12-04T11:43:45Z earth-and-environment

The spatial temporal regime of stream flow of the conterminous U.S. in connection with indices of global atmospheric circulation 2007-12-01T14:35:09Z Boris Shmagin Carol A. Johnston Scott Bridgham Earth & Environment Long-term stream flow records (1929-1988) from seventy one U.S. Geological Survey gauging stations with drainage area in range 1000-10000 sq mi were analyzed using multivariate statistics. Factor analysis of average annual flow revealed seven patterns of river runoff within seven distinct regions of the territory. This factor model reflected 69% variance of the initial matrix. The second set of stream flow records (1939-1972) from ninety-seven gauging stations was used as control. This set contains all seventy one from first one and additional stations with shorter observation period. Factor analysis of this expended set again yielded seven factors (69% variance of the initial matrix) with very similar spatial distribution of gauging stations.

Every group of watersheds obtained as a factor was presented by one gauging station with time series of annual discharges (1- 05474000, 2- 14321000, 3- 07019000, 4- 0815000, 5- 11186001, 6- 01666000, 7- 06800500) as the most typical for group. For the same time interval, streams represented by all patterns have increasing values (i. e. the positive difference between two time subintervals); but only the positive linear trend for patterns 1 and 7 are statistically significant. 

For the seven typical flow records, monthly average values were obtained from three to five seasons composed from different ensembles of months. 

For each annual time series of the typical seven stream flow patterns, regression equations were obtained from indices of global atmospheric circulation (AO, NAO, NPO and AAO). The equations contain from one to five variables (predictors) and have coefficients of correlation from 32% to 73%. 
 http://precedings.nature.com/documents/1382/version/1 oai:nature.com:10.1038/npre.2007.1382.1 http://dx.doi.org/10.1038/npre.2007.1382.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.62.2 2007-12-03T15:53:55Z biotechnology molecular-cell-biology bioinformatics

A three-dimensional stochastic spatio-temporal model of cell spreading 2007-12-03T15:08:25Z Yuguang P. Xiong Padmini Rangamani Benjamin Dubin-Thaler Michael Sheetz Ravi Iyengar Biotechnology Molecular Cell Biology Bioinformatics Cell motility is important for many physiological processes and the underlying
biochemical reactions motility have been well characterized. Mathematical models, using
the biochemical reactions and focused on different types of spreading behavior have been
constructed and analyzed. In this study, we build on these previous models to develop a
three-dimensional stochastic model of isotropic spreading of mammalian fibroblasts. The model is composed of three actin remodeling reactions that occur stochastically in space and time and are regulated by membrane resistance forces. Numerical simulations indicate that the model qualitatively captures the experimentally observed isotropic cell spreading behavior. We analyzed the effects of varying branching reaction rates, membrane resistance forces and capping protein concentrations on the dynamics of isotropic spreading. The simulations allowed us to identify the range within which branching reaction rates and membrane force values cooperate to yield isotropic spreading behavior. The model predicts increasing capping protein concentration would lead to a linear decrease in average peripheral velocity. We tested this prediction experimentally using varying concentrations of a pharmacologic agent (Cytochalasin D) that caps growing actin filaments. We find that the experimental results agree with the numerical simulations. Thus, a spatio-temporally complex model made up of a simple set of stochastic reactions near the cell surface, when constrained by membrane forces, can yield deterministic behavior as characterized by isotropic cell spreading. http://precedings.nature.com/documents/62/version/2 oai:nature.com:10.1038/npre.2007.62.2 http://dx.doi.org/10.1038/npre.2007.62.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1385.1 2007-12-04T20:16:28Z neuroscience

Face Cognition: A Set of Distinct Mental Abilities 2007-12-03T16:06:29Z Oliver Wilhelm Grit Herzmann Olga Kunina Werner Sommer Neuroscience Perceiving, learning, and recognizing faces swiftly and accurately is of paramount importance to humans as a social species. Though established functional models of face cognition<sup>1,2</sup> suggest the existence of multiple abilities in face cognition, the number of such abilities and the relationships among them and to other cognitive abilities can only be determined by studying individual differences. Here we investigated individual differences in a broad variety of indicators of face cognition and identified for the first time three component abilities: face perception, face memory, and the speed of face cognition. These component abilities were replicated in an independent study and were found to be robustly separable from established cognitive abilities, specifically immediate and delayed memory, mental speed, general cognitive ability, and object cognition. The analysis of individual differences goes beyond functional and neurological models of face cognition by demonstrating the difference between face perception and face learning, and by making evident the distinction between speed and accuracy of face cognition. Our indicators also provide a means to develop tests and training programs for face cognition that are broader and more precise than those currently available).<sup>3,4</sup> http://precedings.nature.com/documents/1385/version/1 oai:nature.com:10101/npre.2007.1385.1 http://hdl.handle.net/10101/npre.2007.1385.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1386.1 2007-12-04T16:17:50Z genetics

Statistical Modeling of Epistasis and Linkage Decay using Logic Regression 2007-12-04T01:08:19Z Thomas Parker P Szűcs W F. Mahaffee John A. Henning Genetics & Genomics Logic regression has been recognized as a tool that can identify and model non-additive genetic interactions using Boolean logic groups. Logic regression, TASSEL-GLM and SAS-GLM were compared for analytical precision using a previously characterized model system to identify the best genetic model explaining epistatic interaction for vernalization-sensitivity in barley. A genetic model containing two molecular markers identified in vernalization response in barley was selected using logic regression while both TASSEL-GLM and SAS-GLM included spurious associations in their models. The results also suggest the logic regression can be used to identify dominant/recessive relationships between epistatic alleles through its use of conjugate operators. http://precedings.nature.com/documents/1386/version/1 oai:nature.com:10101/npre.2007.1386.1 http://hdl.handle.net/10101/npre.2007.1386.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1390.1 2007-12-07T17:54:35Z immunology

Interleukin-10 containing normal human serum inhibits granzyme B release but not perforin release from alloreactive and EBV-specific T cell clones 2007-12-05T07:51:59Z Motoko Nishimura Hideya Sato Hitoshi Okazaki Masahiro Satake Kenji Tadokoro Immunology Interleukin-10 (IL-10), also known as cytokine synthesis inhibitory factor, has pleiotropic effects in immunoregulation and inflammation. It is capable of inhibiting synthesis of pro-inflammatory cytokines like interferon [gamma] (IFN[gamma]), IL-2, IL-3, tumor necrosis factor [alpha] (TNF[alpha]) and granulocyte macrophage colony stimulating factor (GM-CSF) made by cells such as macrophages and T helper Type 1 cells. We observed that normal human serum, derived from a healthy individual but containing large amounts of IL-10 (arbitrarily designated as "IL-10 serum"), inhibited cytotoxic activity and interfered with granzyme B release from alloreactive cytotoxic T cell clones in vitro, but did not affect perforin release. The addition of normal human serum containing high levels of anti-IL-10 IgG (arbitrarily designated as "anti-IL-10 IgG serum") neutralized the inhibitory effects of IL-10 serum. Moreover, we have identified that cytotoxic activity and granzyme B release from an Epstein-Barr virus (EBV)-specific cytotoxic T cell clone was similarly inhibited in the presence of IL-10 serum, while perforin release was unaffected. Anti-IL-10 IgG serum also appeared to neutralize the inhibitory effect of IL-10 serum on an EBV-specific T cell clone. When anti-IL-10 IgG was depleted from anti-IL-10 IgG containing serum (arbitrarily designated as "anti-IL10 IgG free serum"), the neutralizing effect disappeared for both alloreactive and an EBV-specific T cell clone. http://precedings.nature.com/documents/1390/version/1 oai:nature.com:10101/npre.2007.1390.1 http://hdl.handle.net/10101/npre.2007.1390.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1391.1 2007-12-05T14:55:32Z molecular-cell-biology

Molecular mechanisms of the regulation of ATPase cycle in striated muscle 2007-12-05T13:12:53Z Yuri S. Borovikov Olga E. Karpicheva Charles S. Redwood Molecular Cell Biology New data on the molecular mechanism of the regulation of ATPase cycle by troponin-tropomyosin system have been obtained in reconstructed muscle fibers by using the polarized fluorescence technique, which allowed us following the azimuthal movements of tropomyosin, actin subdomain-1 and myosin SH1 helix motor domain during the sequential steps of ATPase cycle. We found that tropomyosin strands "rolling" on thin filament surface from periphery to center at ATPase cycle increases the amplitudes of multistep changes in special arrangement of SH1 helix and subdomain-1 at force generation states. These changes seem to convey to actin monomers and to myosin "lever arm", resulting in enhance of the effectiveness of each cross-bridge work. At high-Ca^2+^ troponin, a shift of tropomyosin strands further to center at strong-binding states increases this effect. At low-Ca^2+^ troponin "freezes" tropomyosin and actin in states typical for weak-binding states, resulting in disturbing the teamwork of actin and myosin. http://precedings.nature.com/documents/1391/version/1 oai:nature.com:10101/npre.2007.1391.1 http://hdl.handle.net/10101/npre.2007.1391.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1392.1 2007-12-05T22:11:35Z development ecology

Numbers, not value, motivate cooperation in humans and orangutans 2007-12-05T21:07:37Z Ellen E. Furlong John E. Opfer Developmental Biology Ecology Cooperation among competitors-whether sharing the burden of wind resistance in the Tour de France, forming price-fixing cartels in economic markets, or adhering to arms-control agreements in international treaties-seldom spreads in proportion to the potential benefits. To gain insight into the minds of uncooperative agents, economists and social psychologists have used the prisoner's dilemma task to examine factors leading to cooperation among competitors. Two types of factors have emerged in these studies: the relative rewards of defecting versus cooperating and breakdowns in trust, forgiveness and communication. The generalizability of economic and social psychological factors, however, relies on the assumption that agents' comparisons of gains and losses (whether for themselves, others, or both) preserves ratio information over arbitrary units, such as dollars and cents, and real rewards, such as food. This assumption is inconsistent with psychophysical studies on how the brain represents quantitative information, which suggests that mental magnitudes increase logarithmically with actual value. Thus, discrimination of two numerical magnitudes improves as the numerical distance between them increases and decreases as the magnitudes increase. Here we show an important consequence of this representational system for economic decision making: in the prisoner's dilemma game, purely nominal increases in the numerical magnitude of payoffs (such as, converting dollar values to cents or whole grapes into grape-parts) has a large effect on cooperative behaviour. Moreover, a logarithmic scaling of the ratio of rewards for cooperation versus defection predicted 97% of variability in observed cooperation, whereas the objective ratio predicted 0% of variability. By linking the brain's system of representing the magnitude of rewards to motivations for cooperative behaviour, these findings suggest that the nature of numerical representations may also account for the subjective value function described by Bernoulli, in which the apparent value of monetary incentives increases logarithmically with actual value. http://precedings.nature.com/documents/1392/version/1 oai:nature.com:10101/npre.2007.1392.1 http://hdl.handle.net/10101/npre.2007.1392.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1393.1 2007-12-13T17:09:50Z development

Chorionic Structures in Maternal Blood 2007-12-05T23:41:17Z Nilo Pereira Luz Developmental Biology Chorionic villi are the exchange structures of the placenta where human fetuses receive oxygen and nutrients from maternal blood, this article reports an improvement of a published method to recover them from the blood of pregnant, women, quotes their number and illustrates their size and trypsin impregnation. The reasons to explain the presence of chorionic structures and villi in the circulating maternal blood, the possible significance of their existence in maternal blood and the mechanisms to remove them are discussed. Their size and trypsin impregnation are illustrated. This paper discusses the significance of the presence of such allogeneic structures in the circulating blood of pregnant women and presents a brief discussion on the role of trypsin and its inhibitor in pregnancy homeostasis. http://precedings.nature.com/documents/1393/version/1 oai:nature.com:10101/npre.2007.1393.1 http://hdl.handle.net/10101/npre.2007.1393.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1394.1 2007-12-06T20:39:27Z bioinformatics

Abundance of intrinsic disorder in SV-IV, a multifunctional androgen-dependent protein secreted from rat seminal vesicle 2007-12-06T13:42:18Z Silvia Vilasi Raffaele Ragone Bioinformatics The potent immunomodulatory, anti-inflammatory and procoagulant properties of the
protein no. 4 secreted from the rat seminal vesicle epithelium (SV-IV) have been
previously found to be modulated by a supramolecular monomer-trimer equilibrium.
More structural details that integrate experimental data into a predictive framework
have recently been reported. Unfortunately, homology modelling and fold-recognition
strategies were not successful in creating a theoretical model of the structural
organization of SV-IV. It was inferred that the global structure of SV-IV is not similar
to any protein of known three-dimensional structure. Reversing the classical approach
to the sequence-structure-function paradigm, in this paper we report on novel
information obtained by comparing physicochemical parameters of SV-IV with two
datasets made of intrinsically unfolded and ideally globular proteins. In addition, we
have analysed the SV-IV sequence by several publicly available disorder-oriented
predictors. Overall, disorder predictions and a re-examination of existing experimental
data strongly suggest that SV-IV needs large plasticity to efficiently interact with the
different targets that characterize its multifaceted biological function and should be
therefore better classified as an intrinsically disordered protein. http://precedings.nature.com/documents/1394/version/1 oai:nature.com:10101/npre.2007.1394.1 http://hdl.handle.net/10101/npre.2007.1394.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1403.1 2007-12-07T21:56:32Z cancer molecular-cell-biology

TMEPAI, a transmembrane TGF-β-inducible protein, sequesters Smad proteins in TGF-β signaling 2007-12-07T04:05:50Z Susumu Itoh Yukihide Watanabe Kiyotoshi Satoh Masako Inamitsu Liang Shi Naoko Nakano Aya Tanaka Eliza Wiercinska Hiroshi Shibuya Peter ten Dijke Mitsuyasu Kato Cancer Molecular Cell Biology Transforming growth factor-[beta] (TGF-[beta]) is a multifunctional cytokine of key importance for controlling embryogenesis and tissue homeostasis. How TGF-[beta] signals are attenuated and terminated is not well understood. Here, we show that TMEPAI, a direct target gene of TGF-[beta] signaling, antagonizes TGF-[beta] signaling by interfering with TGF-[beta] type I receptor (T[beta]RI)-induced R-Smad phosphorylation. TMEPAI can directly interact with R-Smads via a Smad interaction motif (SIM). TMEPAI competes with Smad anchor for receptor activation (SARA) for R-Smad binding, thereby sequestering R-Smads from T[beta]RI kinase activation. In mammalian cells, ectopic expression of TMEPAI inhibited TGF-[beta]-induced PAI-1 production, whereas specific siRNA-mediated knockdown of TMEPAI expression potentiated TGF-[beta]-induced Smad2 phosphorylation and cellular responsiveness by TGF-[beta]. Consistently, TMEPAI inhibits activin-mediated mesoderm formation in _Xenopus_ embryos. Taken together, TMEPAI participates in a negative feedback loop to control the duration and intensity of TGF-[beta] signaling. http://precedings.nature.com/documents/1403/version/1 oai:nature.com:10101/npre.2007.1403.1 http://hdl.handle.net/10101/npre.2007.1403.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1405.1 2007-12-07T22:30:23Z ecology

Predicting species abundance distributions by simultaneously using number and biomass as units of measurement 2007-12-07T12:22:45Z Peter A. Henderson Anne E. Magurran Ecology The universal observation that some species in an ecological community are common, but many more are rare, is neatly encapsulated in a species abundance distribution (SAD)1. However, the shape of the distribution can depend on the currency used to measure abundance 2. Here we show how the SADs for numerical abundance and biomass are related and how this relationship can be used to predict the form of the SAD. When plotted in log numerical abundance, log biomass space, species points lie within an approximately triangular area the limits of which are set by body size range, and the upper limit of abundance in both metrics. Under the simplifying, but reasonable, assumption that the observed scatter of species within this region is random, the shape of the SAD is immediately derived from simple geometrical considerations. For the SAD of numerical abundance this is a power curve. The biomass SAD can be either a power curve or, more frequently, a unimodal curve, which can approximate a log normal. This log triangular random placement model serves as a null hypothesis against which actual communities can be compared. Data from two intensively surveyed local communities indicate that it can give a good approximation, with species scattered within a triangle. Further, we can predict the consequences, for the SAD, of size-selective sampling protocols. We argue that mechanistic models of SADs must be able to account for the relative abundance of species in alternative currencies. Moreover, this approach will shed light on niche packing and may have application in environmental monitoring. http://precedings.nature.com/documents/1405/version/1 oai:nature.com:10101/npre.2007.1405.1 http://hdl.handle.net/10101/npre.2007.1405.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1408.1 2007-12-10T15:13:35Z chemistry earth-and-environment

Analysis of Human Spleen Contamination 2007-12-08T14:41:01Z Martin Kopani Martin Weis Jan Jakubovsky Chemistry Earth & Environment Besides carbon, oxygen and nitrogen, numerous other elements and their compounds are significant in the body of humans and other animals. Accumulation of some elements and their compounds is recognized by clinical and biochemical evaluation. The physical-chemical properties and topical characteristics of elements in tissues may play a crucial role in evaluation their effect on human body. The ^57^Fe Mössbauer measurement was used for evaluation of iron–oxide biomagnetic nanoparticles composition and properties. Absorption spectra of the powdered spleen recorded at 77K and 300K were measured and subsequently analyzed. From fitted data it is possible to obtain material composition as well as discuss the mean particle size (received from decrease hyperfine field in comparison with bulk value). http://precedings.nature.com/documents/1408/version/1 oai:nature.com:10.1038/npre.2007.1408.1 http://dx.doi.org/10.1038/npre.2007.1408.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1411.1 2007-12-13T09:29:12Z microbiology

Persisters show heritable phenotype and generate bacterial heterogeneity and noise in protein expression 2007-12-10T05:41:29Z Jaison Jacob Microbiology Persisters are a small subpopulation of bacteria that survive a lethal concentration of antibiotic without antibiotic resistance genes. Isolation of persisters from normally dividing population is considered difficult due to their slow growth, low numbers and phenotypic shift i.e. when re-grown in antibiotic free medium, they revert to parent population. Inability to isolate persisters is a major hindrance in this field of research. Here we reject the ‘phenotypic shift’ phenomenon exhibited by persisters. Persisters, on the other hand, exhibit a heritable phenotype and can be easily isolated from a normally dividing population that allows their selective growth. Rather than a single subset, they comprise many distinct subgroups each exhibiting different growth rates, colony sizes, antibiotic tolerance and protein expression levels. Clearly, they are one of the sources of bacterial heterogeneity and noise in protein expression. Existence of persisters in normally dividing population can explain some of the unsolved puzzles like antibiotic tolerance, post-antibiotic effect and viable but non-culturable bacterial state. We hypothesize that persisters are aging bacteria. http://precedings.nature.com/documents/1411/version/1 oai:nature.com:10101/npre.2007.1411.1 http://hdl.handle.net/10101/npre.2007.1411.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1416.1 2007-12-17T17:58:14Z molecular-cell-biology

Cell Adhesion: A surprising cohesive force 2007-12-11T13:26:20Z Hugues H. Vasseur Molecular Cell Biology When an experimentalist or a biological mechanism applies an external force onto a cell chemically sticking to its substrate, a reacting "suction" force, due to the slow penetration of the surrounding fluid between the cell and the substrate, opposes to the dissociation. This force can overcome other known adhesive forces when the process is sufficiently violent (typically 10^5^ pN). Its maximal contribution to the total adhesive energy of the cell can then be estimated to 2 10^-3^ J/m2. The physical origin of this effect is quite simple, and it may be compared with that leaning a "suction-cup" against a bathroom wall. We address the consequences of this effect on (i) the separation energy, (ii) the motion of the fluid surrounding the cell, more especially, on the pumping of the fluid by moving cells, and (iii) the inhibition of cell motion. http://precedings.nature.com/documents/1416/version/1 oai:nature.com:10101/npre.2007.1416.1 http://hdl.handle.net/10101/npre.2007.1416.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1421.1 2008-01-04T21:45:26Z biotechnology cancer chemistry

A new potential radiosensitizer: ammonium persulfate modified WCNTs 2007-12-13T10:19:43Z Jian-She Yang Bo-Zhang Yu Wen-Xin Li Biotechnology Cancer Chemistry Radiotherapy plays a very important role in cancer treatment. Radiosensitizers have been widely used to enhance the radiosensitivity of cancer cells at given radiations. Here we fabricate multi-walled carbon nanotubes with ammonium persulfate, and get very short samples with 30-50 nanometer length. Cell viability assay show that f-WCNTs induce cell death significantly. We hypothesize that free radicals originated from hydroxyl and carbonyl groups on the surface of f-WCNTs lead cell damage. http://precedings.nature.com/documents/1421/version/1 oai:nature.com:10101/npre.2007.1421.1 http://hdl.handle.net/10101/npre.2007.1421.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1429.1 2007-12-20T11:49:11Z development ecology molecular-cell-biology plant-biology

Bio-communication of Plants 2007-12-15T14:29:49Z Guenther Witzany Developmental Biology Ecology Molecular Cell Biology Plant Biology Plants communicate with a great variety of symbiotic partners, above and below ground. Constant monitoring of signals of biotic origin as well as abiotic environmental influences allows plants to generate appropriate response behavior. These communication processes are primarily sign-mediated interactions and not simply an exchange of information. They involve active coordination and active organization of a great variety of different behavioural patterns – mediated by signs. http://precedings.nature.com/documents/1429/version/1 oai:nature.com:10101/npre.2007.1429.1 http://hdl.handle.net/10101/npre.2007.1429.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1431.1 2007-12-18T11:30:02Z biotechnology chemistry neuroscience pharmacology

Phytochemical Approach and Bioanalytical Strategy to Develop Chaperone-Based Medications 2007-12-16T18:20:01Z Bernd B. K. Kastenholz Biotechnology Chemistry Neuroscience Pharmacology Currently, no pharmaceuticals for the etiological treatment of degenerative protein-misfolding diseases (e.g., ALS, Alzheimer’s or prion diseases) are commercially available. Therefore, in this technical note theoretical considerations and practical approaches concerning the development of chaperone-based medications from medicinal plants (e.g., Ginkgo biloba) are reviewed and discussed in detail. Phytochaperones and other agents isolated from medicinal plants are proposed to serve as the general basis of drug development in protein-misfolding diseases. http://precedings.nature.com/documents/1431/version/1 oai:nature.com:10101/npre.2007.1431.1 http://hdl.handle.net/10101/npre.2007.1431.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1432.1 2007-12-17T16:37:51Z neuroscience

Effects of Pre- and Post-natal smoke exposure on airway neural responses 2007-12-17T01:14:42Z Zhong.-Xin Wu Vincent Kish Thomas Batchelor Richard Dey Neuroscience Abundant epidemiological data shows that maternal smoking during pregnancy or second-hand smoke exposure during neonatal life and infancy increases the incidence of respiratory illnesses later in life. However, underlying mechanisms initiated in early life but affecting adult disease remain undefined. Neurotrophins, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), are neurotrophic factors essential in promoting and maintaining differentiation, growth, and survival of central and peripheral nervous system. The goal of this proposal is to examine the potential role of neurotrophin release in mediating long-term effects of prenatal and early postnatal smoke exposure. Our studies showed that an initial exposure to smoke during prenatal and early postnatal periods significantly changed lung function, substance P (SP) innervation in trachea and the level of NGF in BAL fluid after re-exposure to smoke on adult (postnatal day (PD) 60). In controls, smoke exposure (PD 28) with a subsequent re-exposure at PD 60 did not affect lung function or SP innervation or NGF levels. PCR array revealed enhanced expression of multiple genes including NGF and its receptor by smoke exposure only during early prenatal periods. These data suggest that a critical period of exposure exists in early periods of development. Increased expression of NGF and its receptor in airway caused by smoke exposure may enhance susceptibility to respiratory illnesses in adult. These findings have obvious and significant implication both for smoking during pregnancy and the effects of second hand tobacco smoke exposure. The study provides evidence that prenatal and early postnatal life are periods of enhanced susceptibility to detrimental effects of cigarette smoke. These effects appear to be mediated through the release of neurotrophic factors like NGF which regulate growth and maturation of the airway during these susceptible periods. http://precedings.nature.com/documents/1432/version/1 oai:nature.com:10101/npre.2007.1432.1 http://hdl.handle.net/10101/npre.2007.1432.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1433.1 2007-12-17T22:56:36Z neuroscience

Koffka's Ring Effect Depends on Thickness, Not Continuity 2007-12-17T06:13:12Z Abigail E. Huang Alice J. Hon Eric L. Altschuler Neuroscience More than 70 years ago Gestalt psychologist Kurt Koffka described a fascinating effect1,2: When a contiguous grey ring is placed on a background half of one shade of grey (different from the ring) and half of another shade of grey, the ring appears to be a homogenous. However, if the ring is slightly divided, now the two halves of the ring appear different shades of grey with the half of the ring on the darker background appearing lighter than the half of the ring on the darker background. The Gestalt principle of continuity in visual perception is invoked to explain this effect. Here we show that in fact when the ring is made thinner it appears heterogeneous even when contiguous. Furthermore, when viewing a thick ring after first viewing a thin ring, the thick ring now too appears heterogenous! These effects are also demonstrated with a colored background and backgrounds with more than two regions. We show that standard simultaneous brightness and color contrast weaken with larger test patches. Thus, Koffka's ring effect is due to vanishingly weak simultaneous contrast for a sufficiently thick ring, not continuity. http://precedings.nature.com/documents/1433/version/1 oai:nature.com:10101/npre.2007.1433.1 http://hdl.handle.net/10101/npre.2007.1433.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1436.1 2007-12-18T14:38:49Z chemistry pharmacology

The concentration of homocysteine-derived disulfides in human coronary artery 2007-12-18T06:55:03Z Mauro Iuliano Gaetano De Tommaso Liberato Ciavatta Raffaele Ragone Chemistry Pharmacology *Background* 
Based on previous findings, we have estimated that, in injured coronary artery tissue, the low molecular weight disulfides homocystine and cysteine-homocysteine, otherwise identified as oxidized homocysteine equivalents (OHcyE), may achieve a total concentration that is higher than the aqueous solubility of homocystine at room temperature. In order to verify whether or not OHcyE could reach their saturation limit in the vascular tissue, we have measured the solubility of homocystine in physiological-like condition.

*Materials and methods* 
The solubility of homocystine has been measured in aqueous sodium chloride solutions at 37 °C by differential pulse polarography based on the reduction of homocystine to homocysteine.

*Results* 
We have estimated that the concentration achieved by OHcyE in injured coronary artery tissue is at least near-saturating, because the solubility of homocystine in physiological-like condition, above which deposition of homocystine and/or cysteine-homocysteine as solid phase occurs, almost exactly matches its value. Near-saturation levels of OHcyE within the vascular tissue means that significant leakage of intracellular fluid can promote OHcyE crystallization in tissue fluids, which may serve to initiate inflammation. 

*Conclusions* 
We speculate that deposition of OHcyE crystals could damage blood vessels and act as a primer of homocysteine-triggered inflammation, thus being along the causal pathway that leads to vascular dysfunction. http://precedings.nature.com/documents/1436/version/1 oai:nature.com:10101/npre.2007.1436.1 http://hdl.handle.net/10101/npre.2007.1436.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1438.1 2008-01-02T21:35:10Z genetics

Genome-wide scanning versus candidate gene approach in the genetic architecture of common diseases. 2007-12-18T18:22:17Z Carlos J. Pirola Silvia Sookoian Genetics & Genomics In the Nature 7 June issue, researchers from the Welcome Trust Case Control Consortium (WTCCC) reported the findings of a large genome-wide association (GWA) study of 14,000 cases of common diseases and 3000 controls studies revealing the role of several loci in the genetic risk of common diseases. 

We wish to emphasize that by making public the access to databases, consortia allow other investigators to search for association between candidate genes and T2D-related phenotypes. As an example we found, in a pilot study enrolling 1100 individuals that SNPs in the CLOCK (i.e. rs1554483 and rs6843722) were associated with hypertension (p value < 0.01, and 0.01, respectively). Interestingly, the same association was found by the WTCCC study (rs1554483, rs4580704, rs6843722 and rs4864548 with p<0.039, 0.014, 0.049 and 0.019). However, these findings were not mentioned by the authors because of the stringent p value criteria logically used by them in the face of a WGA. http://precedings.nature.com/documents/1438/version/1 oai:nature.com:10.1038/npre.2007.1438.1 http://dx.doi.org/10.1038/npre.2007.1438.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1439.1 2007-12-19T14:51:26Z neuroscience pharmacology

Application of the Sensory Contact Model for Pharmacological Studies under Simulated Clinical Conditions 2007-12-19T07:27:09Z Natalia N. Kudryavtseva Damira F. Avgustinovich Natalia P. Bondar Michael V. Tenditnik Irina L. Kovalenko Neuroscience Pharmacology The sensory contact model allows forming different psycho-pathological states (anxious depression, catalepsy, social withdrawal, pathological aggression, cognition disturbances, anhedonia, addictive states etc.) produced by repeated agonistic interactions in male mice and investigating the therapeutic and preventive properties of any drug as well as its efficiency under simulated clinical conditions. This approach can be useful for a better understanding of the drugs’ action in different stages of disease development in individuals. It is suggested that this behavioral approach and pharmacological designs may be applied for the screening of novel psychotropic drugs. 
 http://precedings.nature.com/documents/1439/version/1 oai:nature.com:10101/npre.2007.1439.1 http://hdl.handle.net/10101/npre.2007.1439.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1443.1 2007-12-20T15:10:44Z biotechnology cancer chemistry

Iridium complex, a phosphorescent light-emitting diode material, serves as a novel chemical probe for imaging hypoxic tumor tissues 2007-12-19T23:59:26Z Shaojuan Zhang Masahiro Hosaka Toshitada Yoshihara Yasuhiko Iida Keigo Endo Seiji Tobita Toshiyuki Takeuchi Biotechnology Cancer Chemistry Iridium complex, a promising organic light-emitting diode for next generation television displays, emits phosphorescence. Phosphorescence is quenched by oxygen. We used this oxygen-quenching feature for imaging tumor hypoxia. Red light-emitting iridium complex Ir(btp)~2~(acac) (BTP) presented hypoxia-dependent light emission in culture cell lines, whose intensity was in parallel with HIF-1[alpha] expression. BTP was further applied to imaging five tumors (four from human origin and one from mouse origin) transplanted in athymic mice. All tumors presented a bright BTP-emitting image even 5 min after the injection. The BTP-dependent tumor image peaked at 1 to 2 h after the injection, and was then cleared from tumors within 24 h. The minimal BTP image recognition size was 3 to 4 mm in diameter. Compared with ^18^F-FDG/PET images, BTP delineated a clearer image for a tumor profile. We suggest that iridium complex has a vast potential for imaging hypoxic lesions such as tumor tissues. http://precedings.nature.com/documents/1443/version/1 oai:nature.com:10101/npre.2007.1443.1 http://hdl.handle.net/10101/npre.2007.1443.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1448.1 2007-12-24T15:04:44Z genetics

c-Myc induced changes in higher order rDNA structure accompany growth factor stimulation of quiescent cells 2007-12-21T16:35:52Z Chiou-Nan Shiue Rachel G. Berkson Anthony P. H. Wright Genetics & Genomics Human c-Myc is believed to be a high level coordinator of protein synthesis capacity and cell growth rate, capable of activating transcription by all three nuclear RNA Polymerases. Direct activation of rDNA transcription by c-Myc is functionally conserved in rat cells, despite high divergence in non-coding rDNA sequences, suggesting that this coordinating role is likely to be a general within mammals. Upon re-feeding of starved cells, c-Myc activity enhances the efficiency of RNA Polymerase I and SL1/TIF-1B recruitment to the rDNA and rapidly induces higher order gene loop structures in rDNA chromatin that juxtapose upstream and downstream rDNA sequences. Furthermore c-Myc induced gene-loop formation in rDNA genes occurs independently of rDNA transcription, implying that it may be an early step in the re-programming of quiescent cells as they enter the growth cycle. http://precedings.nature.com/documents/1448/version/1 oai:nature.com:10101/npre.2007.1448.1 http://hdl.handle.net/10101/npre.2007.1448.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1454.1 2007-12-26T20:53:59Z biotechnology development

Modelling Hepatic Endoderm Development: Highly Efficient Differentiation of Human Embryonic Stem Cells to Functional Hepatic Endoderm Requires ActivinA and Wnt3a Signalling. 2007-12-22T08:51:53Z David Hay Judy Fletcher Catherine Payne John D. Terrace Ronald C. J. Gallagher Jan Snoeys Jim Black Davina Wojtacha Kay Samuel Zara Hannoun Anne Pryde Celine Filippi Ian S. Currie Stuart J. Forbes James A. Ross Philip Newsome John Iredale Biotechnology Developmental Biology Human embryonic stem cells (hESCs) are a valuable source of pluripotential primary cells. However, their homogeneous cellular differentiation to specific cell types _in vitro_ has proven difficult thus far. Wnt signalling has been shown to play important roles in coordinating development and we demonstrate that Wnt3a is differentially expressed at critical stages of human liver development _in vivo_. The essential role of Wnt3a in hepatocyte differentiation from hESCs is paralleled by our _in vitro_ model, demonstrating the importance of a physiological approach to cellular differentiation. Our studies provide compelling evidence that Wnt3a signaling is important for coordinated hepato-cellular function _in vitro_ and _in vivo_. In addition, we demonstrate Wnt3a facilitates clonal plating of hESCs capable of hepatic endoderm differentiation. These studies represent an important step forward toward the use of hESC-derived hepatocytes in biomedical applications and has opened the door to high through-put metabolic analysis of human liver function. http://precedings.nature.com/documents/1454/version/1 oai:nature.com:10101/npre.2007.1454.1 http://hdl.handle.net/10101/npre.2007.1454.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1456.1 2007-12-28T00:30:22Z cancer pharmacology plant-biology

Are plants with anti-cancer activity resistant to crown gall? : A test of hypothesis 2007-12-22T10:30:56Z R Srirama BT. Ramesha G. Ravikanth R. Uma Shaanker KN Ganeshaiah Cancer Pharmacology Plant Biology The Crown gall tumour assay (CGTA) is one of several bench top bioassays recommended for the rapid screening of plants with anti-cancer activity. The rationale for the use of the bioassay is that the tumorogenic mechanism initiated in plant tissues by _Agrobacterium tumefaciens_ is in many ways similar to that of animals. Several plant species with anti-cancer activity have already been discovered using this bioassay. However till date no explicit test of an association between anti-cancer activity of plants and their resistance to crown gall formation has been demonstrated. Demonstration of an association could have exploratory potential when searching for plants with anti-cancer activity. In this paper, we determined whether or not a statistically significant association between crown gall resistance and anti-cancer activity exists in plants found in existing published data sets. Our results indicate that plants with anti-cancer activity have a higher proportion of their species resistant to crown gall formation compared to a random selection of plants. We discuss the implications of our results especially when prospecting for newer sources of anti-cancer activity in plants. http://precedings.nature.com/documents/1456/version/1 oai:nature.com:10101/npre.2007.1456.1 http://hdl.handle.net/10101/npre.2007.1456.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1457.1 2007-12-27T00:03:56Z biotechnology genetics bioinformatics

Extracting Functional Modules from Biological Pathways 2007-12-22T22:39:44Z Sihai D. Zhao Yong Li Biotechnology Genetics & Genomics Bioinformatics It has been proposed that functional modules are the fundamental units of cellular function. Methods to identify these modules have thus far relied on gene expression data or protein-protein interaction (PPI) data, but have a few limitations. We propose a new method, using biological pathway data to identify functional modules, that can potentially overcome these limitations. We also construct a network of these modules using functionally relevant PPI data. This network displays the flow and integration of information between modules and can be used to map cellular function. http://precedings.nature.com/documents/1457/version/1 oai:nature.com:10.1038/npre.2007.1457.1 http://dx.doi.org/10.1038/npre.2007.1457.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1461.1 2007-12-28T00:48:53Z genetics bioinformatics

Analysis of DNA structure as a 2D random walk by complex wavelet transform 2007-12-24T15:14:25Z Eugene B. Postnikov Alexander Y. Loskutov Sergey A. Larionov Evgeny V. Ryadchenko Roman V. Kiseliov Genetics & Genomics Bioinformatics We propose the original method of the time-scale wavelet analysis of DNA sequence represented as a 2D walk on a complex plane. Namely, we consider the mapping of two irreducible A − T and G − C sequences into a walk trajectory in the plane AGTC (firstly proposed by M. Gates) as a unique complex-valued function. 
 This function is processed with the new algorithm of the continuous wavelet transform with the Morlet wavelet. This method is based on the representation of the transform’s result as a solution of the specific Cauchy problem for the system of PDE. 
 As an example, we applied the described algorithm to a part of the telomer region of the 22 human chromosome and demonstated the high exactness. Moreover, it is very fast and it provides wide opportunities for the analysis of large genome data samples.
 http://precedings.nature.com/documents/1461/version/1 oai:nature.com:10.1038/npre.2007.1461.1 http://dx.doi.org/10.1038/npre.2007.1461.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1464.1 2007-12-26T21:12:01Z immunology

Interleukin-10 containing normal human serum inhibits granzyme B release but not perforin release from alloreactive and EBV-specific T cell clones 2007-12-25T06:30:35Z Motoko Nishimura Hideya Sato Hitoshi Okazaki Masahiro Satake Kenji Tadokoro Immunology Interleukin-10 (IL-10), also known as cytokine synthesis inhibitory factor, has pleiotropic effects in immunoregulation and inflammation. It is capable of inhibiting synthesis of pro-inflammatory cytokines like interferon γ (IFNγ), IL-2, IL-3, tumor necrosis factor α(TNFα) and granulocyte macrophage colony stimulating factor (GM-CSF) made by cells such as macrophages and T helper Type 1 cells. We observed that normal human serum, derived from a healthy individual but containing large amounts of IL-10 (arbitrarily designated as "IL-10 serum"), inhibited cytotoxic activity and interfered with granzyme B release from alloreactive cytotoxic T cell (CTL) clones _in vitro_, but did not affect perforin release. The addition of normal human serum containing high levels of anti-IL-10 IgG (arbitrarily designated as "anti-IL-10 IgG serum") neutralized the inhibitory effects of IL-10 serum. Moreover, we have identified that cytotoxic activity and granzyme B release from an Epstein-Barr virus (EBV)-specific CTL clone was similarly inhibited in the presence of IL-10 serum, while perforin release was unaffected. Anti-IL-10 IgG serum also appeared to neutralize the inhibitory effect of IL-10 serum on an EBV-specific CTL clone. http://precedings.nature.com/documents/1464/version/1 oai:nature.com:10101/npre.2007.1464.1 http://hdl.handle.net/10101/npre.2007.1464.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1466.1 2007-12-26T23:51:32Z neuroscience

From antenna to antenna: Lateral shift of olfactory memory in bees 2007-12-26T12:49:42Z Lesley J. Rogers Giorgio Vallortigara Neuroscience Honeybees, _Apis mellifera_, readily learn to associate odours with sugar rewards and we show here that recall of the olfactory memory, as demonstrated by the bee extending its proboscis when presented with the trained odour, involves first the right and then the left antenna. At 1-2 hour after training using both antennae, recall is possible only when the bee uses its right antenna but by 6 hours after training the memory has made a lateral shift and can now be recalled only when the left antenna is in use. Long-term memory one day after training is also accessed only via the left antenna. This time-dependent shift from right to left antenna is seen as side biases in responding to odour presented to the bee's left or right side and hence may be manifested in natural behaviour. http://precedings.nature.com/documents/1466/version/1 oai:nature.com:10101/npre.2007.1466.1 http://hdl.handle.net/10101/npre.2007.1466.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1467.1 2008-01-07T14:23:03Z neuroscience

Sex-Related Moral Behavior 2007-12-29T09:40:02Z Alberto Priori Manuela Fumagalli Sara Marceglia Roberta Ferrucci Francesca Mameli Stefano Zago Sergio Barbieri Giuseppe Sartori Stefano Cappa Neuroscience The moral sense is one of the most complex aspects of the human mind. While neurobiological, cognitive and behavioural gender-related differences are increasingly studied and verified, the common belief that morality differs between men and women has not been experimentally investigated. We assessed the impact of gender on moral choices by testing thirty men and thirty women with the Moral Sense Task (MST) (Greene _et al_. 2001, 2004; Koenigs _et al_. 2007). Whereas the two genders did not differ in utilitarian responses to non-moral dilemmas (NM) and to impersonal moral dilemmas (MI), men gave significantly more utilitarian answers to personal moral dilemmas (MP; i.e. that action whose endorsement involves highly emotional decision). These results suggest that the cognitive-emotional processes implied in the evaluation of personal moral dilemmas differ between men and women, possibly reflecting differences in the underlying neural mechanisms. The existence of sex-related determinants of moral judgement may be one of the factors responsible for gender differences in real-life behaviours involving power management, economic decision-making, leadership and aggressive and criminal behaviours. http://precedings.nature.com/documents/1467/version/1 oai:nature.com:10101/npre.2007.1467.1 http://hdl.handle.net/10101/npre.2007.1467.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2007.1473.1 2008-01-01T23:35:34Z genetics neuroscience

Sensory Transduction and Subjective Experience: Expression of eight genes in three senses suggests a radical model of consciousness 2007-12-29T22:36:39Z Chris C. King Genetics & Genomics Neuroscience Recent research into whole genome mapping of the mouse brain has made possible direct investigation of the brain expression of unusual genes. A search of the Allen Brain Atlas database has provided genetic and neuro-anatomical evidence for widespread specific expression in the brain of eight genes specific to sensory transduction, in vision, hearing and touch. A novel biophysical model is proposed for the function of these proteins, in generating the internal model of experiential reality. http://precedings.nature.com/documents/1473/version/1 oai:nature.com:10101/npre.2007.1473.1 http://hdl.handle.net/10101/npre.2007.1473.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2007.1479.1 2008-01-04T09:44:55Z neuroscience

Selective bias in temporal bisection task by number exposition 2007-12-30T14:57:18Z Carmelo Mario Vicario Neuroscience Temporal experience can be modulated by a number of environmental factors such as quantity. Here I show that merely looking at numbers causes a bias in imaginative (but not perceptual) time bisection task that depends on the number’s magnitude. This suggests that automatic shifts of spatial attention to the left and right side, as a result of exposure to numbers, modulates temporal as well as spatial behaviour (2,3,4). This finding suggests that the representation of time and space produce certain patterns in neural maps that are decoded by means of the similar neural mechanisms. http://precedings.nature.com/documents/1479/version/1 oai:nature.com:10.1038/npre.2007.1479.1 http://dx.doi.org/10.1038/npre.2007.1479.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1481.1 2008-01-09T16:23:32Z neuroscience pharmacology

COX inhibition: Catalepsy and Striatum Dopaminergic-GABAergic-Glutamatergic Neurotransmission 2008-01-01T18:05:21Z Hadi Fathi-Moghaddam Mehdi Shafiee Ardestani Meysam Shafiee Ardestani Davood Barzegar-Pourshuraki Amin Gravand Latifeh Navidpour Hojat Ebrahiminik Abbas Shafiee Neuroscience Pharmacology Selective COX-2 and COX-1 inhibitors were administered (i.p. acutely) to normal and parkinsonian rats, followed by the analysis of the striatal dopamine, GABA and glutamate concentrations using the microdialysis technique, simultaneously, the catalepsy of animals was evaluated. Selective COX-2 inhibition showed improving effects on the catalepsy followed by decreasing the striatum glutamatergic-GABAergic and enhancing the dopaminergic neurotransmission. Nonetheless COX inhibition had no significant improving effects on damaged Substantia Nigra Pars Compacta (SNc) neurons. http://precedings.nature.com/documents/1481/version/1 oai:nature.com:10101/npre.2008.1481.1 http://hdl.handle.net/10101/npre.2008.1481.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1482.1 2008-01-02T22:43:38Z chemistry evolutionary-biology

Did nature also choose arsenic? 2008-01-02T00:46:18Z Felisa Wolfe-Simon Paul C. W. Davies Ariel Anbar Chemistry Evolutionary Biology All known life requires phosphorus (P) in the form of inorganic phosphate (PO<sub>4</sub><sup>-</sup> or P<sub>i</sub>) and phosphate-containing organic molecules. P<sub>i</sub> serves as the backbone of the nucleic acids that constitute genetic material and as the major repository of chemical energy for metabolism in polyphosphate bonds. Arsenic (As) lies directly below P on the periodic table and so the two elements share many chemical properties, although their chemistries are sufficiently dissimilar that As cannot directly replace P in modern biochemistry. Arsenic is toxic precisely because As and P are similar enough that organisms attempt this substitution. We hypothesize that ancient biochemical systems, analogous to but distinct from those known today, could have utilized arsenate in the equivalent biological role of phosphate. Organisms utilizing such "weird life" biochemical pathways may have supported a "shadow biosphere" at the time of the origin and early evolution of life on Earth or on other planets. Such organisms may even persist on Earth today, undetected, in unusual niches. http://precedings.nature.com/documents/1482/version/1 oai:nature.com:10101/npre.2008.1482.1 http://hdl.handle.net/10101/npre.2008.1482.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1485.1 2008-01-03T22:03:25Z cancer

Markedly enhanced intratumoral spread and antitumor effect of oncolytic adenovirus expressing decorin 2008-01-03T09:06:36Z Chae-Ok Yun Joo-Hang Kim Il-Kyu Choi Young-Sook Lee Ji Young Yoo A-Rum Yoon Hoguen Kim Daniela G. Seidler Cancer With the aim of improving viral distribution and tumor penetration, we have engineered decorin expressing replication-incompetent (dl-LacZ-DCNG) and -competent (Ad-[DELTA]E1B-DCNG) adenoviruses. In both tumor spheroids and established solid tumors in vivo, administration of dl-LacZ-DCNG resulted in greater transduction efficiency and viral spread throughout the tumor mass. Ad-[DELTA]E1B-DCNG also enhanced viral distribution and tumor spread, leading to an increased anti-tumor effect and survival advantage. Upon histological analysis, Ad-[DELTA]E1B-DCNG also elicited greater percentage of apoptotic cells and extensive necrosis compared to those from untreated or control virus-treated tumors. Furthermore, Ad-[DELTA]E1B-DCNG substantially decreased extracellular matrix components within the tumor tissue, while normal tissue adjacent to the tumor was not affected. Finally, intratumoral administration of Ad-[DELTA]E1B-DCNG did not enhance but inhibited the formation of pulmonary metastases of B16BL6 melanoma cells in mice. Taken together, these data demonstrate the utility of decorin as a dispersion agent and suggest its utility and potential in improving the efficacy of replicating adenovirus-mediated cancer gene therapy. http://precedings.nature.com/documents/1485/version/1 oai:nature.com:10101/npre.2008.1485.1 http://hdl.handle.net/10101/npre.2008.1485.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1486.1 2008-01-04T20:55:24Z bioinformatics

Interoperability With Moby 1.0 - It's Better Than Sharing Your Toothbrush! 2008-01-03T19:12:29Z Mark Wilkinson Bioinformatics The BioMoby project was initiated in 2001 from within the model organism database community. It aimed to standardize methodologies to facilitate information exchange and access to analytical resources, using a consensus driven approach. Six years later, the BioMoby development community is pleased to announce the release of the 1.0 version of the interoperability framework, registry API, and supporting Perl and Java code-bases. Together, these provide interoperable access to over 1400 bioinformatics resources worldwide through the BioMoby platform, and this number continues to grow. Here we highlight and discuss the features of BioMoby that make it distinct from other Semantic Web Service and interoperability initiatives, and that have been instrumental to its deployment and use by a wide community of bioinformatics service providers. The standard, client software, and supporting code libraries are all freely available at http://www.biomoby.org/ http://precedings.nature.com/documents/1486/version/1 oai:nature.com:10101/npre.2008.1486.1 http://hdl.handle.net/10101/npre.2008.1486.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1489.1 2008-01-04T14:10:09Z earth-and-environment

Siberian flood basalt magmatism and Mongolia-Okhotsk slab dehydration 2008-01-04T05:59:05Z Alexei V. Ivanov Konstantin D. Litasov Earth & Environment Experimental data combined with numerical calculations suggest that fast subducting slabs are cold enough to carry into the deep mantle a significant portion of the water in antigorite, which transforms with increasing depth to phase A and then to phase E and/or wadsleyite by solid-solid phase transition. Clathrate hydrates and ice VII are also stable at PT conditions of cold slabs and represent other potential phases for water transport into the deep mantle. Some cold slabs are expected to deflect while crossing the 410 km and stagnate in transition zone being unable to penetrate through 660 km discontinuity. In this way slabs can move a long way beneath continents after long-lived subduction. With time, the stagnant slabs are heated to the temperature of the ambient transition zone and release free H~2~O-bearing fluid. Combining with transition zone water filter model this may cause voluminous melting of overlying upper mantle rocks. If such process operates in nature, magmas geochemically similar to island-arc magmas are expected to appear in places relatively remote from active arcs at the time of their emplacement. Dolerites of the south-eastern margin of the Siberian flood basalt province, located about 700 km from suggested trench, were probably associated with fast subduction of the Mongolia-Okhotsk slab and originated by dehydration of the stagnant slab in the transition zone. We show that influence of the subduction-related deep water cycle on Siberian flood basalt magmatism gradually reduced with increasing distance from the subduction zone. http://precedings.nature.com/documents/1489/version/1 oai:nature.com:10101/npre.2008.1489.1 http://hdl.handle.net/10101/npre.2008.1489.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1490.1 2008-01-04T21:14:28Z biotechnology bioinformatics

Understanding Hydrogen-Bond Patterns in Proteins using a Novel Statistical Model 2008-01-04T13:12:40Z Ofer Rahat Uri Alon Yaakov Levy Gideon Schreiber Biotechnology Bioinformatics Proteins are built from basic structural elements and their systematic characterization is of interest. Searching for recurring patterns in protein contact maps, we found several network motifs, patterns that occur more frequently in experimentally determined protein contact maps than in randomized contact maps with the same properties. Some of these network motifs correspond to sub-structures of alpha helices, including topologies not previously recognized in this context. Other motifs characterize beta-sheets, again some of which appear to be novel. This topological characterization of patterns serves as a tool to characterize proteins, and to reveal a high detailed differences map for comparing protein structures solved by X-ray crystallography, NMR and molecular dynamics (MD) simulations. Both NMR and MD show small but consistent differences from the crystal structures of the same proteins, possibly due to the pair-wise energy functions used. Network motifs analysis can serve as a base for many-body energy statistical energy potential, and suggests a dictionary of basic elements of which protein secondary structure is made. http://precedings.nature.com/documents/1490/version/1 oai:nature.com:10101/npre.2008.1490.1 http://hdl.handle.net/10101/npre.2008.1490.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1492.1 2008-01-08T19:01:39Z development ecology earth-and-environment

Silent Spring - the lost call 2008-01-04T18:39:37Z Michael J. Quinn Mary Ann Ottinger Developmental Biology Ecology Earth & Environment The "silence" in Rachel Carson's Silent Spring1 alludes to the demise of bird populations through reproductive problems and death resulting from exposure to the pesticides of that time, many of which are endocrine active. Endocrine disrupting chemicals (EDCs) are compounds which may interfere with the endocrine system, producing effects that may disrupt the physiologic function of hormones. Early research on EDC exposure in humans and wildlife has focused mainly on reproductive effects of estrogenic chemicals, however recent studies have revealed that effects of estrogenic as well as non-estrogen active chemicals are often more far reaching than the reproductive system, and even mild exposures experienced early in development may have detrimental effects that are maintained throughout adulthood. Here we show trenbolone acetate, an androgen active environmental contaminant used as a growth promoter for cattle, to cause a literal silence in Japanese quail (Coturnix japonica) chicks following a one time embryonic exposure. Vocalizations were not merely lessened; this is the first study to demonstrate an environmental contaminant to cause a complete abolishment of the ability to vocalize. Since many reasons for vocalization in birds are directly linked to survival of the individual and species, the potential for detrimental population effects is a grave possibility for many avian species that may encounter androgen active chemicals in the environment. Many androgen active EDCs are persistent and ubiquitous in distribution, thereforechances for exposure to these chemicals in birds may be high. We hope that powerful, yet subtle effects like the ones presented here will encourage further research with EDCs to expand beyond the traditional focus of reproductive effects of estrogenic chemicals. http://precedings.nature.com/documents/1492/version/1 oai:nature.com:10101/npre.2008.1492.1 http://hdl.handle.net/10101/npre.2008.1492.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1454.2 2008-01-10T17:16:05Z biotechnology development

Modelling Hepatic Endoderm Development: Highly Efficient Differentiation of Human Embryonic Stem Cells to Functional Hepatic Endoderm Requires ActivinA and Wnt3a Signalling. 2008-01-05T09:04:13Z David C. Hay Judy Fletcher Catherine Payne John D. Terrace Ronald C. J. Gallagher Jan Snoeys Jim Black Davina Wojtacha Kay Samuel Zara Hannoun Anne Pryde Celine Filippi Ian S. Currie Stuart J. Forbes James A. Ross Philip Newsome John P. Iredale Biotechnology Developmental Biology Human embryonic stem cells (hESCs) are a valuable source of pluripotential primary cells. However, their homogeneous cellular differentiation to specific cell types _in vitro_ has proven difficult thus far. Wnt signalling has been shown to play important roles in coordinating development and we demonstrate that Wnt3a is differentially expressed at critical stages of human liver development _in vivo_. The essential role of Wnt3a in hepatocyte differentiation from hESCs is paralleled by our _in vitro_ model, demonstrating the importance of a physiological approach to cellular differentiation. Our studies provide compelling evidence that Wnt3a signaling is important for coordinated hepato-cellular function _in vitro_ and _in vivo_. In addition, we demonstrate Wnt3a facilitates clonal plating of hESCs capable of hepatic endoderm differentiation. These studies represent an important step forward toward the use of hESC-derived hepatocytes in biomedical applications and has opened the door to high through-put metabolic analysis of human liver function. http://precedings.nature.com/documents/1454/version/2 oai:nature.com:10101/npre.2008.1454.2 http://hdl.handle.net/10101/npre.2008.1454.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1494.1 2008-01-14T18:35:52Z bioinformatics evolutionary-biology

On the reliability of Bayesian posterior clade probabilities in phylogenetic analysis 2008-01-07T15:38:00Z Graham Jones Bioinformatics Evolutionary Biology This article discusses possible reasons why posterior clade probabilities obtained from Bayesian phylogenetic analyses might be inaccurate. It attempts to list all possible sources of uncertainty and error in Bayesian phylogenetic analysis. The choice of priors on trees has been suggested by several authors as a cause of inaccurate posterior clade probabilities. I argue strongly for using priors based on biological knowledge. Two possible sources of bias which do not seem to have been published before are also discussed. One is a computational problem and the other related to majority rule consensus trees.
 http://precedings.nature.com/documents/1494/version/1 oai:nature.com:10101/npre.2008.1494.1 http://hdl.handle.net/10101/npre.2008.1494.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1495.1 2008-01-08T14:47:30Z ecology bioinformatics

Using Biotic Interaction Networks for Prediction in Biodiversity and Emerging Diseases 2008-01-08T00:30:52Z Christopher R. Stephens Joaquin Giménez Heau Camila González-Rosas Carlos N. Ibarra-Cerdeña Victor Sánchez-Cordero Ecology Bioinformatics Networks offer a powerful tool for understanding and visualizing inter-species interactions within an ecology. Previously considered examples, such as trophic networks, are just representations of experimentally observed direct interactions. However, species interactions are so rich and complex it is not feasible to directly observe more than a small fraction. In this paper, using data mining techniques, we show how potential interactions can be inferred from geographic data, rather than by direct observation. An important application area for such a methodology is that of emerging diseases, where, often, little is known about inter-species interactions, such as between vectors and reservoirs. Here, we show how using geographic data, biotic interaction networks that model statistical dependencies between species distributions can be used to infer and understand inter-species interactions. Furthermore, we show how such networks can be used to build prediction models. For example, for predicting the most important reservoirs of a disease, or the degree of disease risk associated with a geographical area. We illustrate the general methodology by considering an important emerging disease - Leishmaniasis. This data mining approach allows for the use of geographic data to construct inferential biotic interaction networks which can then be used to build prediction models with a wide range of applications in ecology, biodiversity and emerging diseases. http://precedings.nature.com/documents/1495/version/1 oai:nature.com:10101/npre.2008.1495.1 http://hdl.handle.net/10101/npre.2008.1495.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1496.1 2008-01-08T18:53:46Z biotechnology pharmacology

Establishing a multicellular model by three-dimensional cell-assembly technique for metabolic syndrome 2008-01-08T00:55:51Z Mingen Xu Yongnian Yan Renjie Zhang Ri Yao Haixia Liu Xiaohong Wang Biotechnology Pharmacology One of the major obstacles in developing multifunctional drugs for the metabolic syndrome (MS) is lack of in vitro models that capture more complex features of the disease. Here we give the first report that establishes an energy metabolic system model using cell-assembly technique which can assemble cells into designated places to form complex three-dimensional structures. Adipose-derived stromal cells were assembled and induced differentiation into adipocytes and endothelial cells; pancreatic islets were then deposited at designated locations and constituted adipoinsular axis with adipocytes. Analysis of the factors involved in energy metabolism showed our system could capture more physiological and pathophysiological features of the in vivo energy metabolism. Drugs known to have effects on MS showed accordant effects in the systems. Construction and study of such multicellular systems could help us better understand pathogenesis of MS, develop new technologies for drug discovery, and foster applications in tissue engineering and metabolomics profiling. http://precedings.nature.com/documents/1496/version/1 oai:nature.com:10101/npre.2008.1496.1 http://hdl.handle.net/10101/npre.2008.1496.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1497.1 2008-01-08T18:44:30Z neuroscience

Cognitive deficits of schizophrenia: the flower workshop initiative 2008-01-08T13:50:54Z Maria Alice Ornellas Pereira Alfredo Pereira Jr Neuroscience Advancement of research on the neurobiology of the schizophrenic brain has revealed a complex of factors, from genetic tendencies affecting the development of brain structure to functional impairment caused by defective molecular signaling. Recently, the attention of psychiatrists and mental health professionals has been directed to the presence of cognitive deficits, responsible for most of the obstacles to the social insertion of patients.The schizophrenic person has a difficulty to manage the flux of consciousness in social interactions. We address this difficulty with the Flower Arrangement Workshop, a methodology of Psycho-Social Rehabilitation that reduces the vulnerability of the schizophrenic in the social environment. The workshop was offered regularly (18 months) for a group containing 4 schizophrenic subjects.
 http://precedings.nature.com/documents/1497/version/1 oai:nature.com:10.1038/npre.2008.1497.1 http://dx.doi.org/10.1038/npre.2008.1497.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1499.1 2008-01-08T22:01:04Z biotechnology earth-and-environment

Potential and environmental concerns of ethanol production from sugarcane molasses in Pakistan 2008-01-08T20:29:41Z Tahir Rashid Zafar Altaf Biotechnology Earth & Environment Energy security and climate change imperatives require large-scale substitution of petroleum-based fuels as well as improved vehicle efficiency4. Biofuels have become one of the fastest growing markets in the world - at 15% growth a year. In fact, until recently, Pakistan was the second largest exporter of sugarcane ethanol to the European Union - a preferential status we have since lost because of WTO obligations and dumping complaints. Several distilleries have planned to close down in light of this fact. Instead of curbing production of fuel ethanol, however, we should redirect it to the domestic market. Pakistan produces around 2 million tons molasses annually and over 90% is exported earning only $47 million. This quantity of molasses will produce over 500 million liters of ethanol to earn $144 million by export or save $63.5 million by blending with fuel. Blending of ethanol will reduce the transport sector GHG emissions by 3.6 million metric tons. http://precedings.nature.com/documents/1499/version/1 oai:nature.com:10101/npre.2008.1499.1 http://hdl.handle.net/10101/npre.2008.1499.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1502.1 2008-01-14T14:05:23Z chemistry pharmacology plant-biology

New source for L-iditol and taxanes 2008-01-09T06:06:24Z Liu Xi-Kui Liu Jian-Jun Chemistry Pharmacology Plant Biology We describe the first report of the recovery of L-iditol and Taxane from an angiosperm- Yunnanopilia longistaminata (W.Z.Li) C.Y.Wu et D.Z.Li (Opiliaceae). Two taxane compounds and L-iditol were isolated from the tender burgeon of Yunnanopilia longistaminata, and their structure were identified as Taxayunnansin B, Taxumairol E and L-iditol on the basis of NMR and MS spectrum, respectively. It is a new plant source for L-iditol and taxanes. http://precedings.nature.com/documents/1502/version/1 oai:nature.com:10101/npre.2008.1502.1 http://hdl.handle.net/10101/npre.2008.1502.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1505.1 2008-01-10T14:51:54Z cancer chemistry bioinformatics

Chemistry Crowdsourcing and Open Notebook Science 2008-01-09T19:29:24Z Jean-Claude Bradley Kevin Owens Antony Williams Cancer Chemistry Bioinformatics This is a pre-proposal written for the NSF program CDI (Cyber-Enabled Discovery and Innovation) in Jan 2008.

The current system of dissemination of scientific data and knowledge is far less efficient than it needs to be to facilitate improved collaborative science, especially considering current publication vehicles and infrastructure. There is a growing movement promoting more Open Science with the belief that a more transparent scientific process can perform far more effectively. The logical extension of this concept is full transparency - exposing a researcher's complete record of progress to the public in near real time. Not only will such a process enable ongoing data sharing it also provides an opportunity to develop collaborative communities of scientists and, at the conclusion of data acquisition, can enable communal extraction of conclusions when necessary. We have named this approach Open Notebook Science and have demonstrated its implementation and feasibility with the UsefulChem project, started in the summer of 2005, with the aim of synthesizing novel anti-malarial compounds. Our system currently uses free hosted services using general blog and wiki functions to facilitate replication across any scientific domains. These services are not chemically intelligent and are limited to text and graphic based data sharing only. For Open Notebook Chemistry the ability to intelligently manipulate, manage and search chemical structures and associated data is necessary and we have demonstrated proof of concept capabilities by integrating with the ChemSpider service, a free access online database managing chemical structures and focused on developing a structure centric community for chemists. This work will require the development of a chemically intelligent software platform to extend the capabilities of both the blog and the wiki environment for managing Open Notebook Science. The exposure of raw experimental procedures and data in a semantically rich format will enable the participation of both human and autonomous agents in the process of scientific discovery. This phenomenon of spontaneous group intelligence, referred to as "Crowdsourcing", has proven valuable in several contexts. Already, productive collaborations have been forged within the UsefulChem project with groups from Indiana University, Nanyang Technological University, the National Cancer Institute and UC San Francisco. http://precedings.nature.com/documents/1505/version/1 oai:nature.com:10.1038/npre.2008.1505.1 http://dx.doi.org/10.1038/npre.2008.1505.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1506.1 2008-01-09T22:11:41Z neuroscience

Physiological Mechanisms Underlying Motion-Induced Blindness 2008-01-09T19:37:05Z Camilo Libedinsky Tristram Savage Margaret Livingstone Neuroscience Visual disappearance illusions - such as motion-induced blindness (MIB) - are commonly used to study the neural underpinnings of visual perception. In such illusions a salient visual target becomes perceptually invisible. Previous studies are inconsistent regarding the role of primary visual cortex (V1) in these illusions. Here we provide physiological and psychophysical evidence supporting a role for V1 in generating MIB. http://precedings.nature.com/documents/1506/version/1 oai:nature.com:10101/npre.2008.1506.1 http://hdl.handle.net/10101/npre.2008.1506.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1513.1 2008-01-15T11:15:30Z biotechnology bioinformatics plant-biology

Tendril, adhesive disc and super adhesive effect of climbing plant 2008-01-12T02:20:08Z Wenli Deng Biotechnology Bioinformatics Plant Biology Understanding the super adhesion mechanism of biological system is of great scientific interest and a prerequisite for bioinspired design of adhesive systems. To investigate the versatile climbing plant requires the development of new methods. Here I present strategies to fully study the super adhesive effect of climbing plant _Parthenocissus tricuspidata_ by the first time measuring the mass and the attached area of single adhesive disc, by further determining the microscopic structure and the adhesive strength of single adhesive disc and by finally elucidating the adhesion mechanism in cellular and molecular level using the classical theories and the proposed new hypothesis and model. I have measured that a single mature adhesive disc has an average mass of only about 0.0005 g, an average attached area of about 1.22 sq mm and an adhesive force of about 13.7 N. I have found that a single adhesive disc can on average support a weight produced together by the stem, leaf, branchlet and tendril which is 260 times greater than its own weight during the growing, and can sustain the maximum pulling force which is 2,800,000 times higher than that produced by its own weight. Microscopic experiments show some new microstructures which have never been reported and reveal that the adhesive disc has super adhesive property which inspires us to fabricate a lot of mimic adhesives that have potential applications in biomedical science, bioelectronics and space science and technology. http://precedings.nature.com/documents/1513/version/1 oai:nature.com:10101/npre.2008.1513.1 http://hdl.handle.net/10101/npre.2008.1513.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1514.1 2008-01-14T17:20:32Z chemistry earth-and-environment

Lattice Parameters of Calcite in the PT-Plane to 7.62 Kb and 800 K 2008-01-13T01:38:53Z Michael J. Bucknum Chemistry Earth & Environment Lattice parameters (a & c) of powdered, polycrystalline calcite in the trigonal-hexagonal system have been determined as a function of pressure and temperature using a hydrothermal diamond anvil cell (DAC), that has been separately described, and a synchrotron x-ray source. Diffraction data was collected using white synchrotron radiation in an energy dispersive technique (EDXRD). Temperature in the resistance heated hydrothermal DAC was measured by thermocouples to a maximum temperature of 800 K, and pressure was measured by the equation of state (EOS) of water, in which powdered calcite was immersed, to a maximum pressure of 7.62 Kb. The resulting study is an attempt to explore the potential of calcite as a double (P & T) internal x-ray standard for high temperature-high pressure (HTHP) crystallographic studies. http://precedings.nature.com/documents/1514/version/1 oai:nature.com:10101/npre.2008.1514.1 http://hdl.handle.net/10101/npre.2008.1514.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1518.1 2008-01-14T21:59:15Z molecular-cell-biology

Eukaryotic translation initiation machinery can operate in a prokaryotic-like mode without eIF2 2008-01-14T17:04:26Z Ivan N. Shatsky Ilya Terenin Sergey Dmitriev Dmitri Andreev Molecular Cell Biology Unlike prokaryotes, a specialized eukaryotic initiation factor 2 (eIF2), in the form of the ternary complex eIF2*GTP*Met-tRNAiMet is utilized to deliver the initiator tRNA to the ribosome within all eukaryotic cells1. Phosphorylation of eIF2 is known to be central to the global regulation of protein synthesis under stress conditions and infection2. Another distinctive feature of eukaryotic translation is scanning of mRNA 5'-leaders, whose origin in evolution may be relevant to the appearance of eIF2 in eukaryotes. Translation initiation on the hepatitis C virus (HCV) internal ribosome entry site (IRES) occurs without scanning3,4. Whether these unique features of the HCV IRES account for the formation of the final 80S initiation complex is unknown. Here we show that the HCV IRES-directed translation can occur without either eIF2 or its GTPase activating protein eIF5. In addition to the general eIF2- and eIF5-dependent pathway of 80S complex assembly, the HCV IRES makes use of a prokaryotic-like pathway which involves eIF5B, the analogue of bacterial IF25,6, instead of eIF2. This switch from a eukaryotic-like mode of AUG selection to a "bacterial" one occurs when eIF2 is inactivated by phosphorylation, a way with which host cells counteract infection. The relative resistance of HCV IRES-directed translation to eIF2 phosphorylation may represent one more line of defense used by this virus against host antiviral responses and can contribute to the well known resistance of HCV to interferon based therapy. http://precedings.nature.com/documents/1518/version/1 oai:nature.com:10101/npre.2008.1518.1 http://hdl.handle.net/10101/npre.2008.1518.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1520.1 2008-01-21T17:30:50Z microbiology pharmacology bioinformatics

In Silico Docking Analysis of Peptide Deformylase (PDF) - A Novel Target for Prophylaxis of Leptospirosis 2008-01-16T06:21:42Z Virupaksha A. Bastikar Shweta R. Fulsundar Jagdish S. Nair Microbiology Pharmacology Bioinformatics Peptide deformylase (PDF) is a metalloproteinase and executes an essential step in the maturation of proteins in eubacteria, by removing the formyl group from the N-terminal methionine residue of ribosome-synthesized polypeptides. This process is crucial for bacterial survival because mature proteins do not retain N-formyl-methionine, and all known N-terminal peptidases cannot utilize formylated peptides as substrate. Thus, inhibition of PDF is essential to obstruct the bacterial protein maturation process. Antibiotics based on PDF inhibition have the potential to provide the much needed antibacterial activity against most of the major drug-resistant pathogens. This study comprises an implementation of _in-silico_ techniques to validate and map the features of the respective active site of PDF from _Leptospira interrogans_. Our analysis consolidates PDF as a promising target for developing novel alternatives as well as indicates superior affinity of current therapeutic agents towards it. This consequently provides a new insight for leptospirosis treatment. http://precedings.nature.com/documents/1520/version/1 oai:nature.com:10101/npre.2008.1520.1 http://hdl.handle.net/10101/npre.2008.1520.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1521.1 2008-01-16T16:00:34Z neuroscience

Young children do not integrate visual and haptic information 2008-01-16T06:54:59Z Monica Gori Michela Del Viva Giulio Sandini David C. Burr Neuroscience Several studies have shown that adults integrate visual and haptic information (and information from other modalities) in a statistically optimal fashion, weighting each sense according to its reliability. To date no studies have investigated when this capacity for cross-modal integration develops. Here we show that prior to eight years of age, integration of visual and haptic spatial information is far from optimal, with either vision or touch dominating totally, even in conditions where the dominant sense is far less precise than the other (assessed by discrimination thresholds). For size discrimination, haptic information dominates in determining both perceived size and discrimination thresholds, while for orientation discrimination vision dominates. By eight-ten years, the integration becomes statistically optimal, like adults. We suggest that during development, perceptual systems require constant recalibration, for which cross-sensory comparison is important. Using one sense to calibrate the other precludes useful combination of the two sources. http://precedings.nature.com/documents/1521/version/1 oai:nature.com:10101/npre.2008.1521.1 http://hdl.handle.net/10101/npre.2008.1521.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1522.1 2008-01-16T17:21:30Z molecular-cell-biology bioinformatics

Shelling the Voronoi interface of protein-protein complexes predicts residue activity and conservation 2008-01-16T11:56:02Z Benjamin Bouvier Raik Grünberg Michael Nilges Frederic Cazals Molecular Cell Biology Bioinformatics The accurate description of protein-protein interfaces remains a challenging task. Traditional criteria, based on atomic contacts or changes in solvent accessibility, tend to over or underpredict the interface itself and cannot discriminate active from less relevant parts. A recent simulation study by Mihalek and co-authors (2007, JMB 369, 584-95) concluded that active residues tend to be `dry', that is, insulated from water fluctuations. We show that patterns of `dry' residues can, to a large extent, be predicted by a fast, parameter-free and purely geometric analysis of protein interfaces. We introduce the shelling order of Voronoi facets as a straightforward quantitative measure of an atom's depth inside an interface. We analyze the correlation between Voronoi shelling order, dryness, and conservation on a set of 54 protein-protein complexes. Residues with high shelling order tend to be dry; evolutionary conservation also correlates with dryness and shelling order but, perhaps not surprisingly, is a much less accurate predictor of either property. Voronoi shelling order thus seems a meaningful and efficient descriptor of protein interfaces. Moreover, the strong correlation with dryness suggests that water dynamics within protein interfaces may, in first approximation, be described by simple diffusion models. http://precedings.nature.com/documents/1522/version/1 oai:nature.com:10101/npre.2008.1522.1 http://hdl.handle.net/10101/npre.2008.1522.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1523.1 2008-01-16T19:51:03Z ecology

Visual perception of colourful petals reminds us of classical fragments 2008-01-16T15:46:07Z Sophia Rhizopoulou Apostolis Argiropoulos Emmanuel Spanakis Demetris Gikas Nikos Alexandredes Danae Koukos Demetrios Anglos Ecology Colour has attracted the interest and attention of many of the most gifted intellects of all time. Ideas of early thinkers were not -and could not have been- grasped on a scientific level without knowledge of a kind that lay far in the future. One character that is being considered is the colourful surfaces of living tissues, which could hardly have been visualized without a corresponding reference to the microscale parallel. Millions of years before man made manipulated synthetic structures, biological systems were using nanoscale architecture to produce striking optical effects. Here we show the microsculpture of the adaxial surface of flower petals from the asphodel, the Stork's-bill and the common poppy by using optical, scanning electron and atomic force microscopy. Microsculpture has been studied in leaves and pollen grains of higher plants. To the best of our knowledge imaging and nanoscale morphometry of petals has not been reported hitherto. Our findings on flower petals' microsculpture may be linked with aspects on colour revealed from ancient literature. http://precedings.nature.com/documents/1523/version/1 oai:nature.com:10101/npre.2008.1523.1 http://hdl.handle.net/10101/npre.2008.1523.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1524.1 2008-01-17T16:28:08Z genetics

Sensitivity Analysis of Self-Identified Race and Ethnicity (SIRE): Screening for Single Nucleotide Polymorphisms. 2008-01-17T15:23:54Z Toni P. Miles Stephen Hanson LaCreis Kidd Avonne Connor Saeed A. Jortani Genetics & Genomics Within the realm of medical care, Self-Identified Race and Ethnicity (SIRE) categories are promoted as an inexpensive tool to identify underlying genotypic diversity. Scientific opinion is divided about the adequacy of SIRE to serve this function. If genetic diversity can guide medical decisions, it is important to know the effectiveness of genetic screening via SIRE. Proper development of self-reported measures such as SIRE requires sensitivity and specificity studies. These types of formal evaluation are largely absent for SIRE. To begin this formal process, we estimate the sensitivity of SIRE in screening for variant Single Nucleotide Polymorphism (SNP). Our results indicate that the current use of SIRE is inadequate to screen for selected biotransformation related SNP in the N-Acetyl Transferase pathway. The widespread usage of SIRE to screen for genotypic diversity could promote erroneous assignment of patients to disease risk or therapeutic categories. http://precedings.nature.com/documents/1524/version/1 oai:nature.com:10101/npre.2008.1524.1 http://hdl.handle.net/10101/npre.2008.1524.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1526.1 2008-01-18T19:51:35Z biotechnology chemistry genetics molecular-cell-biology bioinformatics

Open Data in Science 2008-01-18T07:27:31Z Peter Murray-Rust Biotechnology Chemistry Genetics & Genomics Molecular Cell Biology Bioinformatics Open Data (OD) is an emerging term in the process of defining how scientific data may be published and re-used without price or permission barriers. Scientists generally see published data as belonging to the scientific community, but many publishers claim copyright over data and will not allow its re-use without permission. This is a major impediment to the progress of scholarship in the digital age. This article reviews the need for Open Data, shows examples of why Open Data are valuable and summarizes some early initiatives in formalizing the right of access to and re-use of scientific data. http://precedings.nature.com/documents/1526/version/1 oai:nature.com:10101/npre.2008.1526.1 http://hdl.handle.net/10101/npre.2008.1526.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1528.1 2008-01-22T15:43:14Z immunology

Modulation of interferon-[alpha] secretion by activated platelets in systemic lupus erythematosus. 2008-01-21T17:10:45Z Pierre Duffau Julien Seneschal Carole Nicco Jean-François Viallard Jean-Luc Pellegrin Bernard Weill Jean-François Moreau Frédéric Batteux Patrick Blanco Immunology Type I interferons play a key role in systemic lupus erythematosus (SLE) pathogenesis as an "IFN signature" is found in the majority of patients with active SLE. Immune complexes are internalized by plasmacytoid dendritic cells (DC) via Fc-[gamma] ReceptorIIA, reach the endosomal compartment and activate IFN-[alpha] secretion through TLR7/9-dependent pathways. Naturally occurring differences in expression of the TLR7/9 gene as well as factors that modulate TLR7/9 expression, including CD154 could therefore contribute to SLE pathogenesis. Although its origin is not elucidated CD154 is hyperexpressed in SLE patients, and is important for the differentiation of autoantibody-secreting cells. We hypothesized that platelets which are an abundant source of CD154, and which can mediate proinflammatory effects could be an actor involved in SLE pathogenesis. Platelets from SLE patients are activated _in vivo_ by circulating immune complexes which are abundant in SLE sera, via a CD32-dependent mechanism. Activated platelets formed aggregates with antigen-presenting cells in SLE patients and enhanced interferon-[alpha] secretion induced by immune-complexes stimulated plasmacytoid DCs. Finally, _in vivo_ depletion of platelets and megakaryocytes in NZBxNZW(F1) lupus prone mice improved all parameters assessing disease activity, whereas transfusion of activated platelets worsened the disease course. Altogether, these data identify platelets as a mediator of SLE pathogenesis and a new therapeutical target. http://precedings.nature.com/documents/1528/version/1 oai:nature.com:10101/npre.2008.1528.1 http://hdl.handle.net/10101/npre.2008.1528.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1529.1 2008-01-22T18:48:50Z cancer chemistry plant-biology

The potential of Manitoba chokecherry as a source of high natural antioxidants 2008-01-22T00:23:14Z Wende Li Farah S. Hosseinian Arnold W. Hydamaka Lynda Lowry Trust Beta Cancer Chemistry Plant Biology Consumption of fruits and vegetables is shown to be beneficial for protecting health and preventing some chronic diseases such as cancer, cardiovascular disease, and stroke. The positive health effects have been mainly due to the contributions of their natural antioxidant capacity. Chokecherry (Prunus virginiana), a unique fruit, is a member of the Rose family and native to North America. Here we demonstrate that chokecherry fruit with strong antioxidant capacity is available in Manitoba, and that its potent antioxidant potential can be developed for health benefits in value-added applications.These findings are useful for developing novel value-added antioxidant products from chokecherry because of its phytochemical profile associated with health protection and prevention of disease. The results provide evidence essential for breeding novel cultivars of fruit plants with strong natural antioxidants. http://precedings.nature.com/documents/1529/version/1 oai:nature.com:10101/npre.2008.1529.1 http://hdl.handle.net/10101/npre.2008.1529.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1530.1 2008-01-23T20:50:57Z chemistry

Hypothetical Allotropes of Carbon Built from 1,4-Cyclohexadiene Rings 2008-01-22T00:29:27Z Michael J. Bucknum Chemistry Disclosure Document #337,466 filed with the U.S. Patent & Trademark Office on August 23, 1993 describes, for the first time in the published literature, certain hypothetical constructions known as 3-,4-connected networks built from 1,4-cyclohexadiene rings, as allotropes of carbon and binaries. These hypothetical structures include an allotrope of carbon of tetragonal symmetry (space group P4(2)/mmc) built entirely from 1,4-cyclohexadiene rings and called glitter, and an allotrope of carbon of orthorhombic symmetry (space group Pmmm) built entirely from 1,4-cyclohexadiene rings, as well, and given another name. http://precedings.nature.com/documents/1530/version/1 oai:nature.com:10101/npre.2008.1530.1 http://hdl.handle.net/10101/npre.2008.1530.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1531.1 2008-01-23T19:02:24Z biotechnology

A novel class of endogenous shRNAs in human cells 2008-01-22T09:16:59Z Tongjun Gu James Q. Yin Yanwei Xu ZhengHua Dai Zhengge Qiu Shenzhong Feng Xiang Yi Ling Jiang Hongjie Zhang Biotechnology Until now it is still not clear how many types and amounts of small RNAs (sRNAs) exist in humans. Here we report the identification of 1258 distinct sRNAs derived from intronic regions of protein-coding genes in human with a new approach. These endogenous short hairpin RNAs (shRNAs) appear to be similar to exogenous shRNAs in structure, have a broad distribution in the stem length, and function as microRNAs (miRNAs), small interfering RNAs (siRNA) and/or piwi-interacting RNAs (piRNAs). Except for a few shRNAs, the majority of shRNAs are not phylogenetically conserved. They are differentially expressed in different cells and at diverse developmental stages. Overall, their expression levels are lower than miRNAs', but can be detected by quantitative real-time PCR and microarrays, implying that like other known sRNAs, this type of shRNAs should have important functions in modulating gene expression, and that they may exist in other genomic regions and many species. http://precedings.nature.com/documents/1531/version/1 oai:nature.com:10101/npre.2008.1531.1 http://hdl.handle.net/10101/npre.2008.1531.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1533.1 2008-01-22T22:24:31Z ecology earth-and-environment

Isoprene Emission and Carbon Dioxide Protect Aspen Leaves from Heat Stress 2008-01-22T21:28:03Z Joseph N. T. Darbah Thomas D. Sharkey David F. Karnosky Ecology Earth & Environment High temperature, especially above 35oC, is known to reduce leaf photosynthetic rate in many tree species. This study investigated the effect of high temperature on isoprene-emitting (aspen) and non- emitting (birch) trees under ambient and elevated CO2 under open field conditions. Aspen trees tolerate heat better than birch trees and elevated CO2 protects both species against moderate heat stress. The increased thermotolerance in aspen trees compared to the birch trees may result from the aspen's ability to produce isoprene. Elevated CO2 increased carboxylation capacity, photosynthetic electron transport capacity and triose phosphate use in both birch and aspen trees. High temperature decreased all of these parameters in birch regardless of CO2 treatment but only photosynthetic electron transport and triose phosphate use at ambient CO2 were reduced in aspen. As temperature rises, non-isoprene-emitting trees will be at a disadvantage and biological diversity and species richness might be lost in some ecosystems. Our results indicate that isoprene emitting tree species will have an advantage over non-isoprene emitting ones under high temperatures. http://precedings.nature.com/documents/1533/version/1 oai:nature.com:10101/npre.2008.1533.1 http://hdl.handle.net/10101/npre.2008.1533.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1513.2 2008-01-23T16:52:07Z biotechnology bioinformatics

Tendril, adhesive disc and super adhesive effect of climbing plant 2008-01-23T01:33:58Z Wenli Deng Biotechnology Bioinformatics Understanding the super adhesion mechanism of biological system is of great scientific interest and a prerequisite for bioinspired design of adhesive systems. To investigate the versatile climbing plant requires the development of new methods. Here I present strategies to fully study the super adhesive effect of climbing plant _Parthenocissus tricuspidata_ by the first time measuring the mass and the attached area of single adhesive disc, by further determining the microscopic structure and the adhesive strength of single adhesive disc and by finally elucidating the adhesion mechanism in cellular and molecular level using the classical theories and the proposed new hypothesis and model. I have measured that a single mature adhesive disc has an average mass of only about 0.0005 g, an average attached area of about 1.22 sq mm and an adhesive force of about 13.7 N. I have found that a single adhesive disc can on average support a weight produced together by the stem, leaf, branchlet and tendril which is 260 times greater than its own weight during the growing, and can sustain the maximum pulling force which is 2,800,000 times higher than that produced by its own weight. Microscopic experiments show some new microstructures which have never been reported and reveal that the adhesive disc has super adhesive property which inspires us to fabricate a lot of mimic adhesives that have potential applications in biomedical science, bioelectronics and space science and technology. http://precedings.nature.com/documents/1513/version/2 oai:nature.com:10101/npre.2008.1513.2 http://hdl.handle.net/10101/npre.2008.1513.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1535.1 2008-01-23T15:31:51Z cancer molecular-cell-biology

Tumor-associated EGFR over-expression specifically activates Stat3 and Smad7 resulting in desensitization of TGF-β signaling 2008-01-23T01:47:56Z Rodney Luwor Lauren Taylor Bo Wang Hong-Jian Zhu Cancer Molecular Cell Biology Transforming Growth Factor-[beta] (TGF-[beta]) and Epidermal Growth Factor (EGF) signaling pathways are both independently implicated as key regulators in tumor formation and progression. Here, we demonstrate that activation of the tumor-associated and over-expressed EGFR desensitizes TGF-[beta] signaling and its cytostatic regulation through specific Stat3 activation and Smad7 induction. In normal and tumor human cell lines, reduction of TGF-[beta]-mediated Smad2 phosphorylation, nuclear translocation and Smad3 target gene activation were observed where EGFR is over-expressed, but not in cells which expressed EGFR at normal levels. The EGFR downstream signaling molecules phosphatidyinositol-3 Kinase (PI3K) or mitogen-activated protein kinase/ERK kinase (MEK) are not responsible for the down-regulation of TGF-[beta] signaling since blockade of them by specific pharmacological inhibitors LY294002 and U0126 had little effects on the sensitivity of TGF-[beta] signaling. We identified Stat3 as a signaling molecule activated specifically and persistently by over-expressed EGFR, but not by normal levels. Importantly, Stat3 is responsible for the reduced TGF-[beta] sensitivity, since its knockdown by siRNA restored TGF-[beta] signaling sensitivity. Furthermore, over-expressed EGFR, through Stat3 activates Smad7 promoter activity, increasing its protein levels, which is a negative regulator of TGF-[beta] signaling. Consequently, cells were re-sensitized to TGF-[beta] when Smad7 expression was reduced using siRNA. Therefore we establish a novel EGFR-Stat3-Smad7-TGF-[beta] signaling molecular axis where tumor-associated over-expression of EGFR in epithelial cells results in hyperactivation of Stat3, which activates Smad7 expression, compromising the TGF-[beta]'s cytostatic regulation of epithelium and consequent tumor formation. http://precedings.nature.com/documents/1535/version/1 oai:nature.com:10101/npre.2008.1535.1 http://hdl.handle.net/10101/npre.2008.1535.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1537.1 2008-01-23T21:12:01Z bioinformatics

A Handy Script to Implement Genetic Models in R 2008-01-23T20:30:35Z Wei Zhang Bioinformatics Genome-wide associations between genotypic and phenotypic data often assume certain genetic models. A handy script in R was written to implement three commonly used genetic models: additive, dominant and recessive models. This script can be easily inserted into more complicated programs to facilitate high-throughput association studies. http://precedings.nature.com/documents/1537/version/1 oai:nature.com:10.1038/npre.2008.1537.1 http://dx.doi.org/10.1038/npre.2008.1537.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1539.1 2008-01-24T14:53:00Z microbiology pharmacology bioinformatics

The spread of antimalarial drug resistance: A mathematical model with practical implications for ACT drug policies 2008-01-24T05:15:48Z Wirichada Pongtavornpinyo Shunmay Yeung Ian Hastings Arjen Dondorp Nicholas Day Nicholas White Microbiology Pharmacology Bioinformatics Most malaria-endemic countries are implementing a change in antimalarial drug policy to artemisinin combination therapy (ACT). The impact of different drug choices and implementation strategies is uncertain. A comprehensive model was constructed incorporating important epidemiological and biological factors and used to illustrate the spread of resistance in low and high transmission settings. The model predicts robustly that in low transmission settings drug resistance spreads faster than in high transmission settings, and that in low transmission areas ACTs slows the spread of drug resistance to a partner drug, especially at high coverage rates. This effect decreases exponentially with increasing delay in deploying the ACT and decreasing rates of coverage. A major obstacle to achieving the benefits of high coverage is the current cost of the drugs. This argues strongly for a global subsidy to make ACTs generally available and affordable in endemic areas. http://precedings.nature.com/documents/1539/version/1 oai:nature.com:10101/npre.2008.1539.1 http://hdl.handle.net/10101/npre.2008.1539.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1541.1 2008-01-25T16:20:48Z ecology genetics evolutionary-biology

New Spontaneous Model of Fibrodysplasia Ossificans Progressiva 2008-01-25T14:33:39Z Bruce Rothschild Larry Martin Robert Timm Ecology Genetics & Genomics Evolutionary Biology We report the first known example of spontaneous, naturally occurring fibrodysplasia ossificans progressiva (FOP) in a mammal. The Southeast Asian mouse deer of the genus _Tragulus_ (Artiodactyla: Tragulidae) have an osseous sheath covering the lower back and upper thigh region consistent with the clinical definition of FOP. This heterotophic bone deposition is sex related apparently with a genetic basis - it only occurs in males and is lacking in females; it is present in all adults males, including both wild obtained and zoo bred animals. _Tragulus_ may offer the opportunity to examine many of the disease's most significant attributes experimentally. http://precedings.nature.com/documents/1541/version/1 oai:nature.com:10101/npre.2008.1541.1 http://hdl.handle.net/10101/npre.2008.1541.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1542.1 2008-01-25T22:35:00Z cancer development ecology bioinformatics

Motif analysis of amphioxus, lamprey and invertebrate estrogen receptors and amphioxus and human estrogen-related receptors: Towards a better understanding of estrogen receptor evolution 2008-01-25T20:54:35Z Michael E. Baker Charlie Chandsawangbhuwana Cancer Developmental Biology Ecology Bioinformatics *Background.* The origins of steroid-dependent regulation of the vertebrate estrogen receptor (ER) are poorly understood. Genes with statistically significant sequence similarity to vertebrate ERs have been found in lamprey, a basal vertebrate, and amphioxus, a basal chordate. Motif analysis of these sequences provides an opportunity to investigate early events in the evolution of the ER.
*Results.* We used artificial intelligence-based software to construct twelve motifs specific to the estrogen-binding domain of ER[alpha] and ER[beta] in land vertebrates and teleosts. We mapped these ER-specific motifs onto the sequences of lamprey, amphioxus, invertebrate and selected vertebrate ERs and amphioxus and human estrogen-related receptor (ERR). We find that lamprey ER contains eleven motifs common to ERs in the training set. In contrast, amphioxus ER contains only six motifs. Various invertebrate ERs contain either seven or eight motifs. Unexpectedly, human and amphioxus ERRs contain nine of the twelve motifs, despite extensive sequence divergence during the descent of chordate ERs and ERRs from a common ancestor. We mapped the twelve motifs onto a multiple alignment of human, lamprey and amphioxus ERs, which depicted residues in human ER[alpha] that are known to bind estradiol. There is excellent conservation of these key residues in lamprey ER and poor conservation in amphioxus ER. Out of seventeen residues on human ER[alpha] that bind estradiol, sixteen and six are identical in lamprey and amphioxus ER, respectively. A phylogenetic tree of ERs and ERRs reveals a long branch for amphioxus ER, which is in agreement with the low sequence and motif similarity between amphioxus ER and other ERs.
*Conclusions.* There are significant differences between _B. floridae_ ER and vertebrate ERs in the steroid-binding domain as measured by motif analysis and percent of amino acids that are known to stabilize estradiol in human ER[alpha]. This suggests that novel steroids regulate transcriptional activity of _B. floridae_ ER. The absence in lamprey ER of motif 10, which maps to the c-terminus half of [alpha]-helix 9, may be important in recognition of novel estrogens, such as 15[alpha]-hydroxy-estradiol. 
 http://precedings.nature.com/documents/1542/version/1 oai:nature.com:10101/npre.2008.1542.1 http://hdl.handle.net/10101/npre.2008.1542.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1543.1 2008-01-28T15:35:26Z genetics evolutionary-biology

A Genome-Wide Analysis Reveals Significant Overlap of Transcription and DNA Repair in Stationary Phase Yeast 2008-01-27T20:07:37Z Aviv de Morgan Leonid Brodsky Yefim Ronin Eviatar Nevo Abraham Korol Yechezkel Kashi Genetics & Genomics Evolutionary Biology The association between transcription and DNA repair is acknowledged as a player in the generation of mutations in a non-random fashion in prokaryotes and eukaryotes. Previous studies demonstrated that the transcription complex is capable of directing DNA repair to sites of transcription. This process is especially important to growth-arrested cells, in which many DNA repair capacities are diminished; it may also lead to mutations preferentially in transcribed genes. Using microarray analysis of growth-arrested yeast cultures, we demonstrated on a genomic scale, the co-localization of a DNA-turnover marker, indicative of DNA-repair-associated DNA synthesis, with genes persistently transcribed during stationary phase. This may serve as a clue regarding the non-random manner in which non-dividing cells may potentially mutate in the absence of replication, solely as a result of their inherent, transcriptional stress response. http://precedings.nature.com/documents/1543/version/1 oai:nature.com:10101/npre.2008.1543.1 http://hdl.handle.net/10101/npre.2008.1543.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1544.1 2008-01-28T19:53:58Z chemistry pharmacology

Formulation and in vitro Evaluation of Eudragit L100 piroxicam 2008-01-27T20:33:29Z Mostafa Saffari Malihe Shahbazi Mehdi Shafiee Ardestani Chemistry Pharmacology The aim of this study was to formulate and evaluate controlled release preparations of a water-insoluble drug using Copolymers synthesized from acrylic and methacrylic acid
esters (Eudragit L 100) as the retardant material. Microspheres were prepared by solvent evaporation method using an alcohol / liquid paraffin system. Span60 was used as the droplet stabilizer. The prepared microspheres were characterized for their micromeritic properties and drug loading, as well as by differential scanning calorimetry. The in vitro release studies were performed first in pH1.2 and then pH 6.8, phosphate buffer. The prepared microspheres were yellow, and spherical in shape. The drugloaded microspheres showed 71-85% of entrapment and release was extended up to 7 h. The differential scanning calorimetry thermographs showed stable character of drug in the drug-loaded microspheres and revealed the absence of drug-polymer interactions. The best-fit release kinetics was achieved with Higuchi plot. The release of drug was influenced by the drug to polymer ratio and particle size that was found to be diffusion controlled.
 http://precedings.nature.com/documents/1544/version/1 oai:nature.com:10.1038/npre.2008.1544.1 http://dx.doi.org/10.1038/npre.2008.1544.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1547.1 2008-01-29T13:38:49Z immunology microbiology pharmacology

Role and immunomodulatory profile of histamine receptors by H1 and H2 antagonists 2008-01-29T10:31:06Z Trivendra Tripathi Mohd. Shahid Mashiatullah Siddiqui Rahat Khan Immunology Microbiology Pharmacology The present study was designed to delineate the immunomodulatory role of histamine receptors (H1- and H2-) on induction of antibody response to sheep red blood cells (SRBC), as well as the antibody generation profile, in rabbit system, systemically. The rabbits in two groups received pheniramine (H1-receptor antagonist) and ranitidine (H2-receptor antagonist), respectively, via intramuscular route and were immunized with SRBC intravenously to evaluate suppression or enhancement of antibody responses in sem. A third, control group, received vehicle and were immunized in a similar manner. Histamine released from effector cells (mast cells and basophils) _in vivo_ during inflammatory reactions could influence a detectable antibody response to SRBC as early as day 7-postimmunization (post-I), which lasted until day 28- post-I. Pheniramine-treated rabbits had significantly (*Pa ≤ 0.05 and **Pa ≤ 0.01) more suppressed total serum antibody (IgM + IgG) to SRBC as compared to ranitidine-treated ad cotrol rabbits, while ranitidine-treated rabbits showed different pattern (suppressed or enhanced) during the whole study period. Ranitidine suppressed total antibody level at days 7- and 14- post-I, and enhanced at days 21- and 28- post-I. IgM suppression at day 7- and enhancement at days 14-, 21- and 28- post-I, while IgG suppression during whole study period, as compared to control group was significant (*Pa ≤ 0.05 and **Pa ≤ 0.01) as assessed by direct hemagglutination assay* ad whole SBC-ELISA method**. Here we report that histamine receptor type 2 (H2R)-antagonists have a dominant role on immunosuppression and in immunoregulation of humoral immune responses. Histamine receptor type 2 (H2R)-antagonists are mainly involved in B cell differentiation and proliferation over histamine receptor type 1 (H1R)-antagonists. http://precedings.nature.com/documents/1547/version/1 oai:nature.com:10101/npre.2008.1547.1 http://hdl.handle.net/10101/npre.2008.1547.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1549.1 2008-01-30T17:25:02Z pharmacology

Apoptotic gene expression in neuropathic pain 2008-01-30T15:13:06Z Dario Siniscalco Catia Giordano Carlo Fuccio Livio Luongo Annalucia Migliozzi Francesco Rossi Sabatino Maione Pharmacology Pain initiated or caused by a primary lesion or dysfunction in the nervous system is defined as neuropathic pain. It results from direct injury to nerves in the peripheral or central nervous system and is associated with several clinical symptoms. Neuropathic pain treatment is extremely difficult, as it is a very complex disease, involving several molecular pathways. Excitatory or inhibitory pathways controlling neuropathic pain development show altered gene expression, caused by peripheral nerve injury.
This study used several experimental pain models to demonstrate the occurrence of programmed cell death in the centers controlling pain induction and maintenance, such as spinal cord and pre-frontal cortex. We combined behavioural, molecular and morphological approaches to assess the involvement of bcl-2 gene family and caspases in neuropathic pain. Chronic constriction injury (CCI) and spared nerve injury (SNI) of rodent sciatic nerve induced the appearance of pain-like behaviours, such as hyperalgesia and allodynia. An early (2-3 days post-CCI) apoptosis appeared in the spinal cord neurons as the pro-apoptotic bax gene increased (320±19%). The incidence of apoptosis appeared to be limited to the first few days following nerve injury. Subsequently, increased expression of anti-apoptotic bcl-2 family genes may inhibit further neuron loss. SNI triggered apoptotic pathway and caspases activation in pre-frontal cortex 7, 14, and 21 days post-injury. Among the time-points analyzed, RT-PCR analysis showed increased expression of the bax/bcl-2 ratio (40±2%), bid (16±2%), caspase-1 (84±3%), caspase-8 (53±6%), caspase-9 (25±6%), caspase-12 (58±2%), TNF (32±2%) genes in the cortex by 7 days post-injury. Western blot analysis showed increased active Caspase-3 protein levels in the cortex at 3, 7, 14, and 21 post-surgery. This study shows that apoptotic genes could be an useful pharmacological target in neuropathic pain controlling.
 http://precedings.nature.com/documents/1549/version/1 oai:nature.com:10.1038/npre.2008.1549.1 http://dx.doi.org/10.1038/npre.2008.1549.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1550.1 2008-01-31T16:16:21Z biotechnology

Dual expression recombinase based (DERB) single vector system for high throughput screening and verification of protein interactions in living cells 2008-01-30T22:10:03Z JianPing Lu Laura Beatty Jehonathan Pinthus Biotechnology Identification of novel protein interactions and their mediators is fundamental in understanding cellular processes and is necessary for protein-targeted therapy. Evidently high throughput formatting of these applications in living cells would be beneficial, however no adequate system exists. We present a novel platform technology for the high throughput screening and verification of protein interactions in living cells. The platform's series of Dual Expression Recombinase Based (DERB) destiny vectors individually encode two sets of recombinase recognizable sequences for inserting the protein open reading frame (ORF) of interest, two sets of promoters and reporter tags in frame with the ORFs for detecting interactions. Introduction into living cells (prokaryotic and eukaryotic) enables the detection of protein interactions by fluorescence resonance energy transfer (FRET) or bimolecular fluorescence complementation (BiFC). The DERB platform shows advantages over current commercialized systems by DERB vectors validated through proof-of-principle experiments and the identification of an unknown interaction. http://precedings.nature.com/documents/1550/version/1 oai:nature.com:10101/npre.2008.1550.1 http://hdl.handle.net/10101/npre.2008.1550.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1550.2 2008-02-01T18:31:26Z biotechnology molecular-cell-biology

Dual expression recombinase based (DERB) single vector system for high throughput screening and verification of protein interactions in living cells 2008-01-31T16:32:44Z Jian-Ping Lu Laura Beatty Jehonathan Pinthus Biotechnology Molecular Cell Biology Identification of novel protein interactions and their mediators is fundamental in understanding cellular processes and is necessary for protein-targeted therapy. Evidently high throughput formatting of these applications in living cells would be beneficial, however no adequate system exists. We present a novel platform technology for the high throughput screening and verification of protein interactions in living cells. The platform’s series of Dual Expression Recombinase Based (DERB) destiny vectors individually encode two sets of recombinase recognizable sequences for inserting the protein open reading frame (ORF) of interest, two sets of promoters and reporter tags in frame with the ORFs for detecting interactions. Introduction into living cells (prokaryotic and eukaryotic) enables the detection of protein interactions by fluorescence resonance energy transfer (FRET) or bimolecular fluorescence complementation (BiFC). The DERB platform shows advantages over current commercialized systems by introducing recombinase based cloning and compatible accepting vectors validated through proof-of-principle experiments and the identification of an unknown interaction. http://precedings.nature.com/documents/1550/version/2 oai:nature.com:10101/npre.2008.1550.2 http://hdl.handle.net/10101/npre.2008.1550.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1560.1 2008-02-01T19:24:54Z immunology microbiology molecular-cell-biology

Allicin from garlic suppresses TNF-α and augments IFN-γ expressions in monocyte cultures from patients with Vaginitis 2008-02-01T09:49:44Z Najmul Islam Jawed Iqbal Nazarul Hasan Zeeshan Fatima Hamida Thakur Nazia Hasan Abbas Ali Mahdi Tamkin Khan Farzana Bano Irfan Ahmad Ansari Immunology Microbiology Molecular Cell Biology Objective: We tried to explore beneficial effects of allicin- a natural antioxidant from garlic in the possible management of vaginitis. 
Methods: Peripheral blood mononuclear cells (PBMC’s) were isolated from blood of patients having vaginal infections as well as normal healthy subjects as per our published protocol. Monocytes (MN’s) from above PBMC’s were adhered, rested overnight and cultured without or with varying doses of allicin (0-500 ng/ml). Some cultures received SN50 and SN50M (100 ug/ml). After 24 hrs cultures, the cells were harvested and the supernatants subjected to secreted TNF-α and sIFN-γ assays by ELISA. Treated/untreated harvested cells were subjected to glutathione peroxidase (GPx) activity assay.
Results: We show involvement of inflammatory cytokines and reactive oxygen species (ROS) in vaginitis. Augmented secreted TNF-α and decreased sIFN-γ levels were observed in monocyte cultures of vaginal patients. Relative to healthy controls, a decrease by 2.5-fold in glutathione peroxidase (GPx) activity in cultures of vaginal patients was observed. Treatment with allicin from garlic appreciably decreased secreted TNF-α with simultaneous amelioration in sIFN-γ and GPx activity. Allicin (500 ng/ml) ameliorated GPx activity by ~ 2.16-folds in patient monocyte cultures. The anti-oxidant and anti-inflammatory actions of allicin induced in monocyte cultures of vaginal infection patients were mediated via NF-κB.
Conclusion: Thus, the above results may help in understanding the use of allicin as an adjunct in vaginal infection therapy, and in turn, may address the globally female health.
 http://precedings.nature.com/documents/1560/version/1 oai:nature.com:10.1038/npre.2008.1560.1 http://dx.doi.org/10.1038/npre.2008.1560.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1561.1 2008-02-01T19:18:49Z cancer molecular-cell-biology

Beneficial role of allicin from garlic in cervical cancer 2008-02-01T12:21:32Z Irfan Ahmad Ansari Najmul Islam Cancer Molecular Cell Biology Introduction: Cervical cancer remains a global health concern for females. Thus, in order to control cervical cancer, attempts are being made by researchers globally to somehow induce programmed cell death in the said cancerous cells. Wide spectrums of molecules are being probed for its ability to induce apoptosis in cervical cancer cells. Focus has now shifted in exploring natural compounds having antioxidant and anti-inflammatory molecules that may induce apoptosis in cancerous cells. Thus, we have employed allicin from garlic- a natural antioxidant, to probe the above in the present study.
Objective: To probe whether or not allicin from garlic, a natural antioxidant, induces apoptosis in monocytes from patients with cervical cancer.
Results: Allicin (500 ng/ml) reduced cell viability to 27% after 24 hours of treatment. Moreover, allicin-induced apoptosis was ascertained by measuring the activity of caspase-3, caspase-8 and caspase-9-like proteases in allicin treated and untreated monocytes from cervical cancer patients. Monocyte co-cultured with allicin for 24 hrs exhibited higher activity of caspase-3 followed by caspase-8 and caspase-9 like proteases, thereby indicating that the activation of caspase-3 like proteases was associated with reduced cell survival and apoptotic death of allicin-treated cervical cancer monocytes. This was ascertained by pre-treatment of cancer cells with cell permeable inhibitor Z-VAD-FMK (caspase-3 inhibitor), Z-IETD-FMK (caspase-8 inhibitor) and Z-LEHD-FMK (caspase-9 inhibitor) followed by allicin for 24 hrs (p<0.001). In this case, the cell viability assay showed that the presence of Z-VAD-FMK inhibitor blocked the effect of allicin on the viability of cancer monocytes (p<0.001).
Conclusion: Allicin from garlic may act as an adjunct in the chemotherapy of cervical cancer.
 http://precedings.nature.com/documents/1561/version/1 oai:nature.com:10.1038/npre.2008.1561.1 http://dx.doi.org/10.1038/npre.2008.1561.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1562.1 2008-02-01T21:19:02Z microbiology molecular-cell-biology

Azadirachta indica induced suppression of Mycobacterium tuberculosis secreted proteins in human monocyte 2008-02-01T12:38:05Z Jawed Iqbal Ajay Kumar Najmul Islam Microbiology Molecular Cell Biology The H37Rv strain of MTB was grown in modified Sauton’s medium till mid-log phase. Peripheral blood mononuclear cells (PBMC) were isolated by density gradient sedimentation on Ficoll-Paque separation medium. Adherent monocytes obtained from PBMC’s were infected with H37Rv for 90 min. in the ratio of 1:1 (1 bug: 1 cell). Thereafter, after washing, infected cells were co-cultured with varying doses of neem extract for 24 hrs, and harvested subsequently. Modulation of secreted TNF-[alpha], iNOS and MTB Ag85 complex expressions in culture supernatants was estimated by ELISA.
We report the high basal expression of secreted tumor necrosis factor-[alpha] (TNF-[alpha]), inducible nitric oxide synthase (iNOS) and MTB Ag85 complex in MTB-infected monocytes was suppressed by neem extract in a dose-dependent manner (P<0.001 for all). A concentration of 1ug/ml of neem extract showed a suppression by ~ 2.5-fold (P<0.001), 1.7-fold (P<0.001) and 1.8-fold (P<0.001) in the expressions of
secreted TNF-[alpha], iNOS and MTB Ag85 respectively in 24 hr culture supernatants of MTB-infected monocytes.
Thus, neem extract seems to be a potential future adjunct for in-depth studies in the management of tuberculosis. http://precedings.nature.com/documents/1562/version/1 oai:nature.com:10.1038/npre.2008.1562.1 http://dx.doi.org/10.1038/npre.2008.1562.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1563.1 2008-02-01T18:25:26Z neuroscience

Posterior parietal cortex controls spatial attention through modulation of anticipatory alpha rhythms 2008-02-01T13:23:17Z Paolo Capotosto Claudio Babiloni Gian Luca Romani Maurizio Corbetta Neuroscience A dorsal fronto-parietal network, including regions in intra-parietal sulcus (IPS) and frontal eye field (FEF), has been hypothesized to control the allocation of spatial attention to environmental stimuli. One putative mechanism of control is the de-synchronization of electroencephalography (EEG) alpha rhythms (~8-12 Hz) in parieto-occipital cortex in anticipation of a visual target. We show that brief interference by transcranial magnetic stimulation (rTMS) with preparatory activity in right IPS or right FEF while subjects attend to a spatial location impairs identification of target stimuli ~2 seconds later. Moreover, the visual deficit relates to the disruption of anticipatory (pre-stimulus) alpha desynchronization and its topography in parieto-occipital cortex. After right IPS stimulation, the degree to which alpha desynchronization is suppressed predicts the speed of visual identification. These results demonstrate the causal role of posterior parietal cortex in the control of visuo-spatial attention exerted through the synchronization of visual neurons. http://precedings.nature.com/documents/1563/version/1 oai:nature.com:10101/npre.2008.1563.1 http://hdl.handle.net/10101/npre.2008.1563.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1564.1 2008-02-04T14:11:09Z ecology

Global Eradication of Lymphatic Filariasis: The Value Of Chronic Disease Control in Parasite Elimination Programs 2008-02-02T16:14:33Z Edwin Michael Mwele N. Malecela Mihail Zervos James W. Kazura Ecology The ultimate goal of the global programme against lymphatic filariasis is eradication through irrevocable cessation of transmission using 4 to 6 years of annual single dose mass drug administration. The costs of eradication, and logistical and managerial impediments to executing national and regional control programmes, and scientific uncertainty about transmission endpoints, are challenges to the success of this effort, especially in areas of high endemicity where financial resources are limited. We used a combined analysis of empirical community data describing the association between infection and chronic disease prevalence, mathematical modelling, and economic analyses to identify and evaluate the feasibility of setting an infection target level at which the chronic pathology attributable to lymphatic filariasis - lymphoedema of the extremities (elephantiasis) and hydroceles - becomes negligible in the face of continuing transmission as a first stage option in achieving the elimination of this parasitic disease. The results show that microfilaria prevalences below a threshold of 3.55% at a blood sampling volume of 1 ml could constitute readily achievable and sustainable targets to control disease due to lymphatic filariasis. They also show that as a result of the high marginal cost of curing the last few individuals to achieve elimination, maximal benefits can occur at the disease control threshold. Indeed, a key finding from our coupled economic and epidemiological analysis is that when initial uncertainty regarding eradication occurs and prospects for improving information to resolve such uncertainty over time exist, it is economically beneficial to adopt a flexible, sequential, eradication strategy based on controlling chronic disease initially. These results suggest that it may be optimal to set phased targets for the elimination of lymphatic filariasis, starting with disease control followed by intensified efforts to eradicate transmission as better knowledge regarding transmission dynamics and issues of implementation feasibility becomes evident. They also illustrate the importance of taking explicit accounts of uncertainties, multi-staged endpoints, and the value of embedding flexibility in the decision making process when determining optimal parasite eradication strategies. http://precedings.nature.com/documents/1564/version/1 oai:nature.com:10101/npre.2008.1564.1 http://hdl.handle.net/10101/npre.2008.1564.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1565.1 2008-02-04T17:35:11Z ecology evolutionary-biology

Altruism among relatives and non-relatives 2008-02-02T21:50:40Z Howard Rachlin Bryan A. Jones Ecology Evolutionary Biology The amount of their own monetary reward that undergraduate participants claimed they were willing to forgo, in order to give $75 to another person, decreased hyperbolically as social distance increased between the participant and the other person. Relatives tended to be ranked at closer social distances than were non-relatives. However, even at the same social distance, participants were willing to forgo significantly more money for the benefit of relatives than for the benefit of non-relatives. These results imply that altruism is determined by factors in addition to social distance. http://precedings.nature.com/documents/1565/version/1 oai:nature.com:10101/npre.2008.1565.1 http://hdl.handle.net/10101/npre.2008.1565.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1537.2 2008-02-05T13:52:04Z bioinformatics

A Handy Script to Implement Genetic Models in R 2008-02-04T17:10:26Z Wei Zhang Bioinformatics Genome-wide associations between genotypic and phenotypic data often assume certain genetic models. A handy script in R was written to implement three commonly used genetic models: additive, dominant and recessive models. This script can be easily inserted into more complicated programs to facilitate high-throughput association studies. http://precedings.nature.com/documents/1537/version/2 oai:nature.com:10.1038/npre.2008.1537.2 http://dx.doi.org/10.1038/npre.2008.1537.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1567.1 2008-02-08T18:36:57Z immunology

Effect of hyperglycemia on inflammatory markers in patients with Type 2 Diabetes 2008-02-05T03:45:46Z Rajeev Goyal Abul F. Faizy Najmul Islam Immunology The role of inflammation in causation of both Diabetes and its complications has gained acceptance. Initially, hyperglycemia was thought to be the factor causing inflammation, but recently, obesity has gained attraction as probable cause of inflammation. We have studied the levels of markers of inflammation in Diabetic patients, with uncontrolled hyperglycemia, before and after treatment. The results indicate that hyperglycemia significantly causes increase in inflammatory markers like TNF-α and IL-6, which further contribute to pathogenesis of Diabetes mellitus type 2 as well as its complications such as atherosclerosis and neuropathy. http://precedings.nature.com/documents/1567/version/1 oai:nature.com:10.1038/npre.2008.1567.1 http://dx.doi.org/10.1038/npre.2008.1567.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1574.1 2008-02-12T15:28:18Z genetics

Global Awakening in Genetic Counseling 2008-02-07T02:24:39Z Janice Edwards Jacquie Greenberg Margaret Sahhar Genetics & Genomics The article by Ricki Lewis, Nature, Volume 449,October 18, 2007, correctly points out that the genetic counseling profession is on the "verge of being discovered by the rest of the world". The rapid recognition of genes associated with single-gene disorders and complex conditions has deepened our understanding of the role of genetics in health and illness. The impact of genetic conditions on individuals and families, particularly in ethical, legal and psychosocial arenas, requires specially trained professionals to work in this unique and growing dimension of healthcare. The Transnational Alliance for Genetic Counseling (TAGC) represents fifteen countries currently providing genetic counselor education across five continents. http://precedings.nature.com/documents/1574/version/1 oai:nature.com:10101/npre.2008.1574.1 http://hdl.handle.net/10101/npre.2008.1574.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1576.1 2008-02-07T18:43:58Z genetics microbiology evolutionary-biology

Tuberculosis vaccine strain _Mycobacterium bovis_ BCG Russia is a natural _recA_ mutant 2008-02-07T10:54:35Z Peter M. Keller Erik C. Boettger Peter Sander Genetics & Genomics Microbiology Evolutionary Biology The current tuberculosis vaccine is a live vaccine derived from _Mycobacterium bovis_ and attenuated by serial _in vitro_ passaging. All vaccine substrains in use stem from one source, strain Bacille Calmette-Guérin. However, they differ in regions of genomic deletions, antigen expression levels, immunogenicity, and protective efficacy. As a RecA phenotype increases genetic stability and may contribute restricting the ongoing evolution of the various BCG substrains, we aimed to inactivate _recA_ by allelic replacement in BCG vaccine strains representing different phylogenetic lineages (Pasteur, Frappier, Denmark, Russia). Homologous gene replacement was successful in three out of four strains. However, only illegitimate recombination was observed in BCG substrain Russia. Sequence analyses of _recA_ revealed that a single nucleotide insertion in the 5' part of _recA_ led to a translational frameshift with an early stop codon making BCG Russia a natural _recA_ mutant. At the protein level BCG Russia failed to express RecA. According to phylogenetic analyses BCG Russia is an ancient vaccine strain most closely related to the parental _M. bovis_. Our data suggest that _recA_ inactivation in BCG Russia occurred early and is in part responsible for its high degree of genomic stability, resulting in a substrain that has less genetic alterations than other vaccine substrains with respect to _M. bovis_ AF2122/97 wild type. http://precedings.nature.com/documents/1576/version/1 oai:nature.com:10101/npre.2008.1576.1 http://hdl.handle.net/10101/npre.2008.1576.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1584.1 2008-02-11T22:30:36Z neuroscience

Perceptual deficits and inattention in schizophrenia 2008-02-09T18:15:33Z John R. Skoyles Bernt C. Skottun Neuroscience A number of investigators have found perceptual deficits in schizophrenic subjects. It has also been indicated that those with schizophrenia suffer from reduced attention. This raises the possibility that their perceptual deficits may wholly or in part reflect attentional effects. The present study used computer simulations to examine the potential effects of inattention on performance measures determined with three psychophysical methods: the Two Alternative Forced Choice (2-AFC) Staircase Method, the Two Alternative Forced Choice (2-AFC) Fixed Stimuli Method, and the Yes/No Method. It is shown that both 2-AFC methods are susceptible to attentional effects but, in contrast, the Yes/No Method may allow for the differentiation of attentional effects from sensory sensitivity and subjective criterion effects. The simulations indicate that it may be possible to control for attention effects by using Yes/No Method in combination to a 2AFC method. http://precedings.nature.com/documents/1584/version/1 oai:nature.com:10.1038/npre.2008.1584.1 http://dx.doi.org/10.1038/npre.2008.1584.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1585.1 2008-02-13T19:32:12Z ecology

A model explaining some bryozoan colonies 2008-02-11T19:45:48Z Dawid Mazurek Ecology Although the colonialism surely developed independently in Graptolithoidea and Bryozoa, both groups share similar patterns of astogeny. One of the common features is the presence of morphological gradients. Many attempts at its explanation were made for more than a half of the century. This paper discusses a new model of the late astogeny in some bryozoan colonies, showing a cyclic reappearance of secondary zones of astogenetic change and astogenetic repetition that cannot be explained by the single morphogen gradient theory. http://precedings.nature.com/documents/1585/version/1 oai:nature.com:10.1038/npre.2008.1585.1 http://dx.doi.org/10.1038/npre.2008.1585.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1586.1 2008-02-12T16:41:49Z chemistry

Chemical Physics of Phonons & Superconductivity: A Heuristic Approach 2008-02-12T01:35:43Z Michael J. Bucknum Chemistry Several lines of thought are pursued in an attempt to further clarify the role played by phonons in the theory of superconductivity. The central results of BCS theory are examined in the context of anharmonicity in the phonon motion and the role that Badger's rule of spectroscopy can play in simplifying and making more chemically intuitive the nature of the mechanism of superconductivity. http://precedings.nature.com/documents/1586/version/1 oai:nature.com:10101/npre.2008.1586.1 http://hdl.handle.net/10101/npre.2008.1586.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1587.1 2008-02-13T09:43:13Z chemistry

Chemical Topology of Crystalline Matter 2008-02-12T02:10:39Z Michael J. Bucknum Chemistry This work is intended as a review and extension of the seminal work in chemical topology developed by the crystallographer A.F. Wells in the 20th century. http://precedings.nature.com/documents/1587/version/1 oai:nature.com:10101/npre.2008.1587.1 http://hdl.handle.net/10101/npre.2008.1587.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1590.1 2008-02-12T21:48:02Z earth-and-environment

Reducing Greenhouse Gas Emissions: Geological Storage of CO2 2008-02-12T14:05:37Z Tara LaForce Earth & Environment Carbon capture and storage (CCS) is the collection of carbon dioxide (CO2) from industrial point sources such as power plants and its injection underground. Much of the technology necessary to capture and inject CO2 into the subsurface already exists and CCS will be an integral part of any strategy to combat anthropogenic climate change until we, as a society, are able to move away from our dependence on fossil fuels. 

There are three options for geological storage of CO2: deep saline aquifers, depleted oil reservoirs and unmineable coal beds. It is the purpose of this presentation to provide a general survey of each of these options. For each geological formation I review (1) The ways in which CO2 could escape into the atmosphere. (2) Current scientific knowledge and uncertainties about the behaviour of CO2 after it is underground -particularly the interactions of water, oil or gas initially present in the geological formation with injected CO2. (3) The overall advantages and disadvantages of each option in terms of technical challenges and cost. http://precedings.nature.com/documents/1590/version/1 oai:nature.com:10.1038/npre.2008.1590.1 http://dx.doi.org/10.1038/npre.2008.1590.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1591.1 2008-02-15T21:07:01Z molecular-cell-biology

Induction of Stress Granule Assembly is Essential for the Orchestration of DNA Damage Response 2008-02-13T08:38:42Z Nicole S. Verkaik Stephan Persengiev Molecular Cell Biology DNA damage provokes several responses including DNA repair, cell cycle regulation and apoptosis that collectively represent the DNA damage response (DDR). Here, we demonstrate that the DDR incorporates the activation of stress granule (SG) formation pathway as a mechanism to process destabilized RNAs. UV irradiation induced the assembly of SGs during the G2 phase and newly formed SGs appeared exclusively in the early G1 phase. SG assembly pathway was activated within the first hours after DNA damage, suggesting that the processing of destabilized RNAs is activated at an early stage. The induction of SGs and RNAi effector protein Argonaute 2 recruitment after UV exposure was independent of ATM and ATR signaling cascades. Apoptosis occurred only in SG-negative cells indicating that SGs promote cell survival after genotoxic stress. Analysis of several DNA damage/repair deficient MEFs revealed that the SG accumulation remained unaltered after UV exposure. Our results show that SGs are an essential component of DDR that is activated in parallel to the DNA damage kinase response networks. http://precedings.nature.com/documents/1591/version/1 oai:nature.com:10101/npre.2008.1591.1 http://hdl.handle.net/10101/npre.2008.1591.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1593.1 2008-02-14T16:33:18Z molecular-cell-biology bioinformatics

On ARS-interacting multifunctional protein p18 2008-02-13T17:15:45Z Viktor Deineko Molecular Cell Biology Bioinformatics Nine aminoacyl-tRNA synthetases with three auxiliary components are forming a multisynthetase complex which is essential component of protein biosynthesis machinery. The smallest auxiliary component p18 takes part in biosynthesis channeling. It is also a regulator of p53 and has tumor suppressing function. Particular structure of this protein is still unknown. Here methods of structural bioinformatics were applied to generate a model of p18 spatial structure suitable for further research. The structure was created using homology modeling. DNA-binding residues of p18 were also derived both from raw sequence and from three-dimensional structure model. http://precedings.nature.com/documents/1593/version/1 oai:nature.com:10.1038/npre.2008.1593.1 http://dx.doi.org/10.1038/npre.2008.1593.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1597.1 2008-02-15T22:17:33Z ecology

Speciation of chilean Rhinocryptidae (Avian) based on their behaviour 2008-02-15T01:08:31Z Alejandro Correa Rueda Jorge Mpodozis Ecology The current classification of the chilean representatives of the passerine family Rhinocryptidae includes eight species. Three of them contain subspecies that don't exhibit clear differences. Moreover, differences among two lineages of _Scytalopus_ genera and two species of _Pteroptochos_ are cryptic. We propose a new methodology based on ecological and behavioural patterns in order to understand the concept of speciation in this group of birds. According to our results, we postulate that there is not a cut criteria to establish differences among three sister lineages of current classification. This way the methodology developed by us does not allow to establish divergence for a given common ancestor. Our methodology allows to establish comparison among previously determined phylogenetic lineages. Our results show how when integrating behaviour and ecological terms as biological traits next to morphological characters of the plumage, it allows us to conclude that there is decrease of the distances among sister lineages in the cluster tree. http://precedings.nature.com/documents/1597/version/1 oai:nature.com:10101/npre.2008.1597.1 http://hdl.handle.net/10101/npre.2008.1597.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1586.2 2008-02-19T15:18:28Z chemistry

Chemical Physics of Phonons & Superconductivity: A Heuristic Approach 2008-02-15T17:03:11Z Michael J. Bucknum Chemistry Several lines of thought are pursued in an attempt to further clarify the role played by phonons in the theory of superconductivity. The central results of BCS theory are examined in the context of anharmonicity in the phonon motion and the role that Badger's rule of spectroscopy can play in simplifying and making more chemically intuitive the nature of the mechanism of superconductivity. http://precedings.nature.com/documents/1586/version/2 oai:nature.com:10101/npre.2008.1586.2 http://hdl.handle.net/10101/npre.2008.1586.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1602.1 2008-02-19T12:08:52Z molecular-cell-biology neuroscience

Altered cholesterol ester cycle in _ex vivo_ skin fibroblasts from Alzheimer patients 2008-02-18T17:15:02Z Alessandra Pani Sandra Dessi Giacomo Diaz Claudia Abete Claudia Mulas Claudia Norfo Marirosa Putzolu Maria Dolores Cannas Christina Doriana Orru Alessandra Mocali Pier Luigi Cocco Paolo La Colla Francesco Paoletti Molecular Cell Biology Neuroscience Recent studies in both animal and cell models of Alzheimer's disease (AD) indicated that sub-cellular cholesterol distribution seems to regulate amyloid-beta (A[beta]) generation in the brain. In particular, cholesterol-esters (CE), rather than total cholesterol levels, appear directly correlated with A[beta] production. Here we observed that, similarly to brain cells, skin fibroblasts obtained from AD patients produce and accumulate more CE than skin fibroblasts from age-matched healthy controls do. AD fibroblasts also exhibited a 2 fold increase in the expression of ACAT1, in addition to lower levels of SREBP2, nCEH, Caveolin-1 and ABCA1 mRNA levels, all of which are involved in the CE cycle. HMGCoA-reductase and LDL-receptor mRNAs levels did not show statistically significant changes in AD, compared to non-AD, cells. Furthermore, although APP mRNA did not significantly vary, neprilysin (NEP), the most important enzyme in the proteolysis of A[beta], was expressed at very low levels in skin fibroblasts of sporadic AD patients. Our results contribute to the concept that AD may be the consequence of a basic and systemic defect in the CE cycle. Moreover, our results identify new possible targets for the diagnosis, prevention, and cure or, at least, amelioration of the symptoms of AD. http://precedings.nature.com/documents/1602/version/1 oai:nature.com:10101/npre.2008.1602.1 http://hdl.handle.net/10101/npre.2008.1602.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1603.1 2008-02-19T19:11:54Z molecular-cell-biology

Precocious activation of APC/C-Cdh1 at pre-anaphase causes genome instability 2008-02-19T11:26:22Z Ayumu Yamamoto Takashi Ushimaru Takanori Ohyoshi Asuka Suzuki Kazuhiro Toda Masaru Ueno Masahiro Uritani Molecular Cell Biology Faithful chromosome segregation and thereby accurate gene transmission are crucial for all organisms. Until proper attachment of the mitotic spindle to the kinetochore is established, the ubiquitin ligase (E3) Cdc20-activated APC/C (anaphase promoting complex/cyclosome) is repressed by the spindle assembly checkpoint (SAC) and sister chromatin cohesion is protected. Mutants defective in SAC fail to arrest at metaphase even in the presence of damaged microtubules. Interestingly, a similar phenomenon occurs in yeast cells defective in Bub2, a negative factor of the mitotic exit network (MEN), which is required for telophase onset, although its precise molecular mechanism is unknown. Here, we show that chromosome missegregation occurs frequently in bub2∆ cells in the presence of damaged microtubules. The loss of Bub2 caused precocious activation of APC/C-Cdh1/Hct1 at pre-anaphase, leading to securin degradation and then separase-mediated cohesin cleavage. Overexpression of CDH1 and CDC14, encoding Cdc14 phosphatase, at pre-anaphase similarly caused chromosome missegregation. Thus, sequential activation of APC/C-Cdc20 and then APC/C-Cdh1 is critical for precise chromosome segregation and precocious activation of APC/C-Cdh1 at pre-anaphase causes genomic instability. Since degradation of human securin is also mediated by APC/C-Cdc20 and APC/C-Cdh1, this study predicts that precocious activation APC/C-Cdh1 in human cells similarly causes genomic instability, and thereby cell death or tumorigenesis. http://precedings.nature.com/documents/1603/version/1 oai:nature.com:10101/npre.2008.1603.1 http://hdl.handle.net/10101/npre.2008.1603.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1606.1 2008-02-19T16:47:25Z ecology

Differences of morphological and ecological characters among lineages of Chilean Rhinocryptidae in relation an sister lineage of Furnariidae. 2008-02-19T15:46:28Z Alejandro Correa Rueda Jorge Mpodozis Michel Sallaberry Ecology Eight species of Rhinocryptidae are recognized from Chile. Moreover, morphological, ecological and behavioral differences among two lineages of _Scytalopus_ and two species of _Pteroptochos_ are unclear. According to our results, there are no decisive criteria differentiating among subspecific sister taxa of _Scelorchilus albicollis_, _S. rubecula_ and _Pteroptochos megapodius_. Here we discuss the speciation of the chilean Rhinocryptidae based in their behaviour. We propose a new methodology based on ecological and behavioural patterns in order to understand the concept of speciation in this group of birds.
 http://precedings.nature.com/documents/1606/version/1 oai:nature.com:10.1038/npre.2008.1606.1 http://dx.doi.org/10.1038/npre.2008.1606.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1608.1 2008-02-29T19:02:36Z genetics plant-biology evolutionary-biology

Structural dynamics and divergence of the polygalacturonase gene family in land plants 2008-02-20T06:42:59Z Soon-Jae Kwon Jae-Han Son Kyong-Cheul Park Hae-Young Oh Pyeung-Hyeun Kim Woo-Hyeon Byeon Nam-Soo Kim Genetics & Genomics Plant Biology Evolutionary Biology A distinct feature of eukaryotic genomes is the presence of gene families. The polygalacturonase (PG) (EC3.2.1.15) gene family is one of the largest gene families in plants. PG is a pectin-digesting enzyme with a glycoside hydrolase 28 domain. It is involved in numerous plant developmental processes. The evolutionary processes accounting for the functional divergence and the specialized functions of PGs in land plants are unclear. Here, phylogenetic and gene structure analysis of PG genes in algae and land plants revealed that land plant PG genes resulted from differential intron gain and loss, with the latter event predominating. PG genes in land plants contained 15 homologous intron blocks and 13 novel intron blocks. Intron position and phase were not conserved between PGs of algae and land plants but conserved among PG genes of land plants from moss to vascular plants, indicating that the current introns in the PGs in land plants appeared after the split between unicellular algae and multicelluar land plants. These findings demonstrate that the functional divergence and differentiation of PGs in land plants is attributable to intronic loss. Moreover, they underscore the importance of intron gain and loss in genomic adaptation to selective pressure. http://precedings.nature.com/documents/1608/version/1 oai:nature.com:10101/npre.2008.1608.1 http://hdl.handle.net/10101/npre.2008.1608.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1612.1 2008-02-21T17:39:19Z genetics bioinformatics

Stochastic and regulatory role of chromatin silencing in genomic response to environmental changes 2008-02-21T14:07:04Z Jung Kyoon Choi Sohyun Hwang Young-Joon Kim Genetics & Genomics Bioinformatics Phenotypic diversity and fidelity can be balanced by controlling stochastic molecular mechanisms. Epigenetic silencing is one that has a critical role in stress response. Here we show that in yeast, incomplete silencing increases stochastic noise in gene expression, probably owing to unstable chromatin structure. Telomere position effect is suggested as one mechanism. Expression diversity in a population achieved in this way may render a subset of cells to readily respond to various acute stresses. By contrast, strong silencing tends to suppress noisy expression of genes, in particular those involved in life cycle control. In this regime, chromatin may act as a noise filter for precisely regulated responses to environmental signals that induce huge phenotypic changes such as a cell fate transition. These results propose modulation of chromatin stability as an important determinant of environmental adaptation and cellular differentiation. http://precedings.nature.com/documents/1612/version/1 oai:nature.com:10101/npre.2008.1612.1 http://hdl.handle.net/10101/npre.2008.1612.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1615.1 2008-02-21T22:43:00Z ecology

Ancient Trephinations in Neolithic People - Evidence for Stone Age Neurosurgery? 2008-02-21T21:56:37Z Juergen Piek Gundula Lidke Thomas Terberger Ecology The authors present the case of a late neolithic skull (14C dating: 1940 calBC) found 1921 at Bölkendorf, 60 km north-easterly of Berlin. It shows a left frontal trephination (53 x 50 mm) and additionally a left temporo-occipital depressed skull fracture (both survived). Microscopic and 3D-CT analyses strongly suggest that the trephination has been performed for medical purposes. http://precedings.nature.com/documents/1615/version/1 oai:nature.com:10101/npre.2008.1615.1 http://hdl.handle.net/10101/npre.2008.1615.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1619.1 2008-02-22T18:44:06Z ecology

Increased risk and benefit simultaneously alter the outcome of territorial fights 2008-02-22T12:54:08Z Tsunenori Koga Satoshi Ikeda Ecology Competition for resource, including territories is seen in a broad range of taxa. There has been much research on factors that determine the intensity and outcome of competitions (e.g. resource holding potentials: RHP, and resource value: RV). No research, however, has shown how different factors can simultaneously alter the intensity and outcome of contests. We investigated the effects of RV on fighting behavior and success in inter-tidal, territorial male crabs. Under natural conditions the larger rival won contests irrespective of whether he was the resident or intruder (i.e. there was no residency effect). We then motivated intruders to fight hard by subjecting them to the threat of predation, and found that they were more likely to win contests. When we also motivated residents to fight hard by placing a female in his burrow (i.e. both rivals were simultaneously motivated to fight due to the perceived increase in resource value), we found that the contests escalated more and that resident males had a slightly increased chance of winning. This is the first report of two factors simultaneously affecting motivation and therefore altering the escalation and outcome of a contest. http://precedings.nature.com/documents/1619/version/1 oai:nature.com:10101/npre.2008.1619.1 http://hdl.handle.net/10101/npre.2008.1619.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1620.1 2008-02-22T21:38:19Z ecology

GESTATION LENGTH OF KARI SHEEP 2008-02-22T14:42:35Z Sohail Ahmad Ecology Previously, the concept of a gestation period of sheep shorter than 121 days was unheard of in the field of sheep biology. Our findings during a farmers’ survey in the Lotkho area of Chitral, Pakistan, revealed that the sheep native to the region, locally called “Kari”, gestates for a period of only three months. This duration is 25-40% short of the usual gestation length and is shorter than ever recorded for the species. The mean and mode gestation length (GL) was 110 and 92 days respectively and was concentrated in three distinct clusters: day 87-95, 120-123 and 151-153, accounting for 52% of all observations. GL was influenced by location, season of conception and lambing and the interaction of location with season; had an estimated repeatability of zero. The mean lambing interval was 224.7 ±5.24 days, ranging between 109 and 467 days. During a trial conducted in a controlled environment, only three out of the 27 copulated ewes conceived, and gestated in 113, 125 and 145 days respectively. Gestation length during the trial supported field findings. The results suggest that GL in Kari sheep is unusual as many ewes gestated in three months, with variations of up to 5 months. Genotype by environment interaction is a possibility. However, reasons for the findings are still not clear and further controlled studies should be carried out to establish and further explore the factor(s) responsible for this unusual and unique manifestation of the Kari with regards to its gestation length. http://precedings.nature.com/documents/1620/version/1 oai:nature.com:10101/npre.2008.1620.1 http://hdl.handle.net/10101/npre.2008.1620.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1621.1 2008-02-25T20:31:11Z biotechnology chemistry

Multifunctional Hybrid Silica Particles for Multicolor Imaging and Multiplex Tasking 2008-02-22T19:23:05Z Sang Man koo Hae Sung Kim Chan Yoon Jung Ha Young Kim Hoe Jin Hah Biotechnology Chemistry Multifunctional submicron particles have recently emerged as great promises for biological applications such as bio-labeling, medical diagnostics, and drug delivery. These particles are non-toxic and have size comparable to biomolecules, becoming very suitable for biomedical applications. The particle structures can be engineered to perform multicolor imaging, as well as multiplex tasking such as site-selective binding, detection, and separation. In addition, these particles can load a large amount of fluorescent dye for signal amplification. Several synthetic techniques have been developed for a variety of submicron particles, including core-shell synthesis, layer-by-layer techniques, multi-block polymer emulsifications, and surface modifications. Silica particles are one of the most extensively studied particles as they can be easily modified with organic functionalities. However, these silica particles usually have only a single type of functional group. Therefore, multiple sequential modification steps have to be employed in order to attach multitasking components such as imaging components, drugs and targeting moieties. For wider biological applications, the development of a simple and efficient preparation method for particles with various types of functionalities is of great importance. Herein, a "ONE-POT"; synthesis of multifunctional hybrid silica (MHS) particles of uniform size and morphology with homogeneously distributed multiple functional moieties is reported. The MHS particles can be tagged with various multitasking components for detection, selective binding, and separation using different functionalities, in an easier and more flexible way than those particles with a single functional group. Moreover, each functional moiety can be further modified with additional organic or inorganic groups. We demonstrate here following abilities of MHS particles: 1) expansion of surface functionality through the reaction with organic or inorganic compounds; 2) multicolor imaging by surface-conjugation with multiple dyes; 3) controlled assembly of 3-dimensional aggregates from two different types of MHS particles; 4) multiplex tasking through dye-tagging and selective binding to a patterned surface. http://precedings.nature.com/documents/1621/version/1 oai:nature.com:10101/npre.2008.1621.1 http://hdl.handle.net/10101/npre.2008.1621.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1431.2 2008-04-09T13:56:55Z chemistry pharmacology plant-biology

Phytochemical Approach and Bioanalytical Strategy to Develop Chaperone-Based Medications 2008-02-24T21:10:23Z Bernd Kastenholz Chemistry Pharmacology Plant Biology Currently, no pharmaceuticals for the etiological treatment of degenerative protein-misfolding diseases (e.g., ALS, Alzheimer’s or prion diseases) are commercially available. Therefore, in this technical note theoretical considerations and practical approaches concerning the development of chaperone-based medications from medicinal plants (e.g., Ginkgo biloba) are reviewed and discussed in detail. Phytochaperones and other agents isolated from medicinal plants are proposed to serve as the general basis of drug development in protein-misfolding diseases. http://precedings.nature.com/documents/1431/version/2 oai:nature.com:10101/npre.2008.1431.2 http://hdl.handle.net/10101/npre.2008.1431.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1627.1 2008-02-26T17:54:06Z ecology earth-and-environment

How could a natural catastrophe impact the ecology of a species? The Nicobar megapode and tsunami 2008-02-25T07:29:26Z Sivakumar Kuppusamy Ecology Earth & Environment This study on the impact of the 2004 tsunami on the Nicobar megapode Megapodius nicobariensis, endemic coastal living bird species in the Nicobar group of islands showed a significant decline (nearly 70%) in the number of individuals when compared to before tsunami populations (Paired sample test, t=2.061, df=14, p<0.05). The tsunami has also adversely influenced the nest-site selection of the megapodes. The post tsunami impact on this species is also expected to be severe, pushing the species into the category of "critically endangered". http://precedings.nature.com/documents/1627/version/1 oai:nature.com:10101/npre.2008.1627.1 http://hdl.handle.net/10101/npre.2008.1627.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1629.1 2008-02-25T22:29:37Z neuroscience

Dynamic gating in the nucleus accumbens: Behavioral state-dependent synchrony with the prefrontal cortex and hippocampus 2008-02-25T21:01:56Z Rifat J. Hussain Aaron J. Gruber Patricio O'Donnell Neuroscience Contextual and sensory information, goals, and the motor plan to achieve them are integrated in the nucleus accumbens (NA). Although this integration needs flexibility to operate in a variety of environments, models of NA function rarely consider changing behavioral states. Here, intracellular recordings in anesthetized rats revealed rapid changes in the synchronization between NA up states and prefrontal cortical (PFC) local field potentials (LFPs). The synchronization of the NA with the PFC and ventral hippocampus also varied over time in awake rats, depending on the behavioral state of the animal: NA LFPs followed hippocampal theta rhythms during spatial exploration, but not during an operant task when they were instead synchronized with slower PFC rhythms. These data indicate that the ability of the NA to follow cortical inputs can rapidly change, allowing for a mechanism that could select an optimal response for a given behavioral condition. http://precedings.nature.com/documents/1629/version/1 oai:nature.com:10101/npre.2008.1629.1 http://hdl.handle.net/10101/npre.2008.1629.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1632.1 2008-02-26T21:44:11Z earth-and-environment

3D computer modeling in micropalaeontology – Late Paleozoic conodonts and foraminifers as example 2008-02-26T17:57:55Z Andrey V. Zhuravlev Yadviga A. Vevel Earth & Environment Three-dimension modeling of fossils is one of the branches of computer using in palaeontology. The branch has wide perspectives but it is hardly developed, especially in micropalaeontology. Proposed method of 3D modelling of microfossils demands no unique and expansive equipment and can be realized practically in any palaeontological laboratory. Lower accuracy of the models developed is not critical for most the fields of their utilization: for teaching purposes, construction of illustrated databases and virtual atlases, and for the display of microfossils to a general audience. http://precedings.nature.com/documents/1632/version/1 oai:nature.com:10101/npre.2008.1632.1 http://hdl.handle.net/10101/npre.2008.1632.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1633.1 2008-02-27T14:13:32Z biotechnology bioinformatics

Open Science: Tools, approaches, and implications 2008-02-26T21:58:37Z Shirley Wu Cameron Neylon Biotechnology Bioinformatics The Pacific Symposium on Biocomputing is an annual meeting whose topics are determined by proposals submitted by members of the community. This document is the proposal for a session on Open Science, submitted for consideration for the PSB meeting in 2009. http://precedings.nature.com/documents/1633/version/1 oai:nature.com:10.1038/npre.2008.1633.1 http://dx.doi.org/10.1038/npre.2008.1633.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1637.1 2008-02-27T18:27:11Z biotechnology chemistry evolutionary-biology

On the status of the Michaelis-Menten equation and its implications for enzymology 2008-02-27T11:55:31Z Sosale Chandrasekhar Biotechnology Chemistry Evolutionary Biology The Michaelis-Menten equation (MME) is considered to be the fundamental equation describing the rates of enzyme-catalysed reactions, and thus the 'physicochemical key' to understanding all life processes. It is the basis of the current view of enzymes as generally proteinaceous macromolecules that bind the substrate reversibly at the active site, and convert it to the product in a relatively slow overall sequence of bonding changes ('turnover'). The manifested 'saturation kinetics', by which the rate of the enzymic reaction (essentially) increases linearly with the substrate concentration ([S]) at low [S] but reaches a plateau at high [S], is apparently modelled by the MME. However, it is argued herein that the apparent success of the MME is misleading, and that it is fundamentally flawed by its equilibrium-based derivation (as can be shown mathematically). Thus, the MME cannot be classed as a formal kinetic equation _vis-a-vis_ the law of mass action, as it does not involve the 'incipient concentrations' of enzyme and substrate; indeed, it is inapplicable to the reversible interconversion of substrate and product, not leading to the expected thermodynamic equilibrium constant. Furthermore, the principles of chemical reactivity do not necessarily lead from the above two-step model of enzyme catalysis to the observed 'saturation kinetics': other assumptions are needed, plausibly the inhibition of product release by the substrate itself. (Ironically, thus, the dramatic graphical representation of the MME encrypts its own fundamental flaw!) Perhaps the simplest indictment of the MME, however, lies in its formulation that the rate of the enzymic reaction tends towards a maximum of k~cat~[E~o~] in the 'saturation regime'. This implies - implausibly - that the turnover rate constant k~cat~ can be known from the overall rate, but independently of the dissociation constant (K~M~) of the binding step. (Many of these arguments have been presented previously in preliminary form.) http://precedings.nature.com/documents/1637/version/1 oai:nature.com:10101/npre.2008.1637.1 http://hdl.handle.net/10101/npre.2008.1637.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1638.1 2008-02-27T18:12:44Z molecular-cell-biology

Constraints of FL Motif on the Targeting and Function of Sodium-Bicarbonate Cotransporter 1 2008-02-27T15:00:02Z Hong C. Li Ali Shawki YoonKyung Park Emily Y Li Kyung-Soo Hahm Joel H. Collier Bryan Mackenzie Manoocher Soleimani Molecular Cell Biology A C-terminal dihydrophobic FL motif plays a vital role in the basolateral targeting of sodium bicarbonate cotransporter 1. To further characterize the role of dihydrophobic FL motif, 1). the FL motif in wild type (PFLS) was reversed to LF (PLFS), 2). the FL motif (PFLS) was shifted upstream (FLPS), and 3). the FL motif (PFLS) was shifted downstream (PSFL). The wild type (PFLS) and its mutant (PLFS) were exclusively expressed on the basolateral membrane by con-focal microscopy, however, the mutant (FLPS) and (PSFL) were predominantly mistargeted to the apical membrane and the cytoplasm, respectively. Functional studies showed that the mutant (PSFL) displayed a remarkably reduced current (p value<0.05 vs wild type). The mutant (PSFL) displayed a more reduced membrane surface expression than the wild type and was co-localized with ER marker. The protein sequence spanning FL motif in kNBC1 C-terminal cytoplasmic tail shows a helical structure, mutants (PLFS) and (PSFL) reduce a-helical contents by circular dichroism study. Reversed FL isn't a constraint for basolateral targeting, but shifting it upstream and downstream are ones. http://precedings.nature.com/documents/1638/version/1 oai:nature.com:10101/npre.2008.1638.1 http://hdl.handle.net/10101/npre.2008.1638.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1639.1 2008-02-28T19:24:26Z chemistry

Covalently bound substrate at the regulatory site triggers allosteric enzyme activation 2008-02-27T21:01:28Z Steffen Kutter Manfred Weiss Georg Wille Ralph Golbik Michael Spinka Stephan König Chemistry The mechanism by which the enzyme pyruvate decarboxylase from yeast is activated allosterically has been elucidated. A total of seven three-dimensional structures of the enzyme, of enzyme variants or of enzyme complexes form two yeast species (three of them reported here for the first time) provide detailed atomic resolution snapshots along the activation coordinate. The prime event is the covalent binding of the substrate pyruvate to the side chain of cysteine 221, thus forming a thiohemiketal. This reaction causes the shift of a neighbouring amino acid, which eventually leads to the rigidification of two otherwise flexible loops, where one of the loops provides two histidine residues necessary to complete the enzymatically competent active site architecture. The structural data are complemented and supported by kinetic investigations and binding studies and provide a consistent picture of the structural changes, which occur upon enzyme activation. http://precedings.nature.com/documents/1639/version/1 oai:nature.com:10101/npre.2008.1639.1 http://hdl.handle.net/10101/npre.2008.1639.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1643.1 2008-03-03T10:11:04Z development genetics molecular-cell-biology

Ablation of smooth muscle myosin heavy chain SM2 increases smooth muscle contractility and results in postnatal death in mice 2008-02-28T23:22:43Z Mei Chi Yingbi Zhou Srikanth Vedamoorthyrao Gopal Babu Muthu Periasamy Developmental Biology Genetics & Genomics Molecular Cell Biology The smooth muscle myosin heavy chains (SMHC) are motor proteins powering smooth muscle contraction. Alternate splicing of SHMC gene at the C-terminus produces SM1, and SM2 myosin isoforms; SM2 (200 kDa) contains a unique 9-amino-acid sequence at the carboxyl terminus, whereas SM1 (204 kDa) has a 43 amino acid non-helical tail region. To date the functional difference between C-terminal isoforms has not been established; therefore, we used an exon-specific gene targeting strategy and generated a mouse model specifically deficient in SM2. Deletion of exon-41 of the SMHC gene resulted in a complete loss of SM2 in homozygous (_SM2^-/-^_) mice, accompanied by a concomitant down-regulation of SM1 in bladders. While heterozygous (_SM2^+/-^_) mice appeared normal and fertile, _SM2^-/-^_ mice died within 30 days after birth. The peri-mortal _SM2^-/-^_ mice showed reduced body weight, distention of the bladder and alimentary tract, and end-stage hydronephrosis. Interestingly, strips from _SM2^-/-^_ bladders showed increased contraction to K^+^ depolarization or M3 receptor activation. These results suggest that SM2 myosin has a distinct functional role in smooth muscle, and the deficiency of SM2 increases smooth muscle contractility, and causes dysfunctions of smooth muscle organs, including the bladder that leads to the end-stage hydronephrosis and postnatal death. http://precedings.nature.com/documents/1643/version/1 oai:nature.com:10101/npre.2008.1643.1 http://hdl.handle.net/10101/npre.2008.1643.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1650.1 2008-03-03T17:40:51Z chemistry

Trigohexagonite: A Rare Quaternary Stoichiometry Network 2008-03-01T08:14:55Z Michael J. Bucknum Bin Wen E.A. Castro Chemistry A rare quaternary stoichiometry network of high hexagonal symmetry (P-6m2) is described. A set of hexagonal fractional crystallographic coordinates, for both an idealized network, and optimized boron and carbon allotropic realizations are described along with their band structures. Both should be metallic phases. http://precedings.nature.com/documents/1650/version/1 oai:nature.com:10101/npre.2008.1650.1 http://hdl.handle.net/10101/npre.2008.1650.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1651.1 2008-03-03T16:27:35Z chemistry

Geometrical-topological correlation in structures 2008-03-01T08:38:22Z Michael J. Bucknum Eduardo A. Castro Chemistry The topology of polyhedra, tessellations and networks is described as to their mapping in Schlaefli space. A description of the topological form index is given and it is applied to these structural classes in terms of their geometries. http://precedings.nature.com/documents/1651/version/1 oai:nature.com:10101/npre.2008.1651.1 http://hdl.handle.net/10101/npre.2008.1651.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1652.1 2008-03-04T17:53:17Z neuroscience

Human microglial cells synthesize albumin in brain 2008-03-01T09:03:39Z Sung-Min Ahn Kyunghee Byun Kun Cho Jin Young Kim Jong Shin Yoo Deokhoon Kim Sun Ha Paek Seung U. Kim Richard J. Simpson Bonghee Lee Neuroscience Albumin has been implicated in Alzheimer's disease since it can bind to and transport amyloid beta, the causative agent; albumin is also a potent inhibitor of amyloid beta polymerization. In a pilot phase study of Human Brain Proteome Project, we found evidence that albumin may be synthesized in immortalized human microglial cells, human primary microglial cells, and human fetal and adult brain tissues. We also found the synthesis and secretion is enhanced upon microglial activation by Amyloid [beta]~1-42~, lipopolysaccharide treatment or human Alzheimer's brain. http://precedings.nature.com/documents/1652/version/1 oai:nature.com:10101/npre.2008.1652.1 http://hdl.handle.net/10101/npre.2008.1652.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1655.1 2008-03-04T18:07:36Z bioinformatics

The What, Why and How of openness in science 2008-03-04T13:18:53Z Konrad U. Foerstner Lars J. Jensen Bioinformatics We give a short introduction to open science followed by an overview of Creative Commons and open source licenses. http://precedings.nature.com/documents/1655/version/1 oai:nature.com:10.1038/npre.2008.1655.1 http://dx.doi.org/10.1038/npre.2008.1655.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1606.2 2008-03-06T17:42:28Z ecology

Differences of morphological and ecological characters among lineages of Chilean Rhinocryptidae in relation an sister lineage of Furnariidae. 2008-03-04T22:13:52Z Alejandro Correa Rueda Jorge Mpodozis Michel Sallaberry Ecology Eight species of Rhinocryptidae are recognized from Chile. Moreover, morphological, ecological and behavioral differences among two lineages of _Scytalopus_ and two species of _Pteroptochos_ are unclear. According to our results, there are no decisive criteria differentiating among subspecific sister taxa of _Scelorchilus albicollis_, _S. rubecula_ and _Pteroptochos megapodius_. Here we discuss the speciation of the chilean Rhinocryptidae based in their behaviour. We propose a new methodology based on ecological and behavioural patterns in order to understand the concept of speciation in this group of birds.
 http://precedings.nature.com/documents/1606/version/2 oai:nature.com:10.1038/npre.2008.1606.2 http://dx.doi.org/10.1038/npre.2008.1606.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1670.1 2008-03-11T17:59:40Z ecology

Biodiversity shapes tree species aggregations in tropical forests 2008-03-10T02:04:21Z Shan-Huah Wu Wei-Chun Chao Chang-Fu Hsieh Ecology Spatial patterns of conspecific trees are considered as the consequences of biological interactions and environmental influences. They also reflect species interactions in plant communities. However, biological attributes are often neglected while deliberating the factors shaping species distributions. As rising attentions are paid to spatial patterns of tropical forest trees, we noticed that seven Center of Tropical Forest Sites and four Forest Dynamic Plots in Asia and America have presented analogously high proportions of species with aggregated conspecific individuals coincidently. This phenomenon is distinctive and repudiates fundamental ecology hypotheses which suggested dispersed distributions of conspecific tropical trees due to intensive density and natural enemy pressures in tropical forests. We believe that similar aggregation patterns shared by these tropical forests implies the existence of structuring forces in biogeographical scale instead of habitat heterogeneity in local community scales as scientists have considered. To approach the factors contributing to this cross-continent spatial pattern of trees, we obtained and reviewed ecosystem attributes, including topography, temperature, precipitation, biodiversity, density, and biomass, of these forests. Here we show that the proportions of aggregated species are actually constants independent of any ecosystem attributes regardless the nature of these tropical forests. However, local biodiversity are the major factor determining the number of aggregated species and the aggregation of large individuals of these forests. Aggregation of large trees declines along rising biodiversity, while the numbers of aggregated species increase permanently along lifting biodiversity. We propose a possible equilibrium and saturated status of the tropical forests in accommodating aggregated species. Furthermore, the tight correlations of biodiversity and species aggregation strongly imply the importance of overlooked biological interactions in shaping the spatial patterns in the tropical forests. http://precedings.nature.com/documents/1670/version/1 oai:nature.com:10101/npre.2008.1670.1 http://hdl.handle.net/10101/npre.2008.1670.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1672.1 2008-03-10T21:11:56Z genetics earth-and-environment plant-biology

Incident light orientation lets C4 monocotyledonous leaves make light work differently 2008-03-10T16:16:00Z Ana S. Soares Simon P. Driscoll Till K. Pellny Enrique Olmos Maria Arrabaça Christine Foyer Genetics & Genomics Earth & Environment Plant Biology Photosynthesis is an important driver of ecosystem sustainability in the face of climate change. Monocotyledonous crop species with C4 photosynthesis such as maize (Zea mays L; corn) and sugar cane are crucial for future food security and biofuel crop requirements, while C4 pasture grasses such as Paspalum are central to natural ecosystems. The global demand for corn will exceed that for wheat and rice by 2020, making it the world's most important crop. Light-driven photosynthesis supports plant biomass production, but plants have also evolved safety valve mechanisms that attenuate the absorption of potentially lethal levels of excess light. The array of survival responses that enables leaves to evade photoinhibition is complex and involves chloroplast and leaf movement as well as the molecular rearrangements that facilitate thermal energy dissipation. Here we report a novel morphological mechanism that allows C4 monocotyledonous leaves to regulate photosynthesis independently on each surface with respect to incident light allowing better adaptation to water deficits and light stress. We show that under abaxial illumination as occurs when monocotyledonous leaves curl in response to water stress the stomata close and photosynthetic metabolism shuts down on the adaxial surface of C4 leaves but these parameters increase in function to the abaxial surface. We discuss how this regulation confers a survival advantage to the C4 relative to C3 leaves which are unable to regulate their dorso-ventral functions in relation to light. http://precedings.nature.com/documents/1672/version/1 oai:nature.com:10101/npre.2008.1672.1 http://hdl.handle.net/10101/npre.2008.1672.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1673.1 2008-03-11T14:44:41Z neuroscience

Functional differentiation within the monkey cortex as revealed by near-infrared spectroscopy 2008-03-10T22:08:52Z Allen Ardestani Felix Darvas Jens Steinbrink Arthur Toga Joaquin M. Fuster Neuroscience The role of prefrontal cortex in working memory (WM) is well established. However, questions remain regarding the topography and “domain-specific differentiation” of different types of information processing in the cortex. While it has been theorized that dorsolateral (DPFC) and ventrolateral (VPFC) prefrontal cortex preferentially process spatial and object WM, respectively, both electrophysiological evidence in the monkey and neuroimaging in the human have largely failed to demonstrate such regional differentiation. In this study we use near-infrared spectroscopy (NIRS) to detect functional changes, across relatively large cortical cell populations, simultaneously from prefrontal and posterior parietal cortices. Imaging data were recorded from a Rhesus macaque performing two types of WM tasks: a spatial task in which the animal had to retain the spatial position of a visual stimulus, and a non-spatial task where he had to retain its color (red or green) during a 20s delay. During performance of the spatial WM task, cerebral activation trends were found in which DPFC exhibited stronger activation than did the VPFC, and posterior parietal cortex maintained higher delay activation than did frontal regions. These differences were less pronounced during performance of the non-spatial task. Additionally, incorrect trials generally elicited lower activations during the delay period than did trials ending with a correct response. Furthermore, NIRS data collected during the performance of a haptic WM task also appear to exhibit inter-regional differences in delay activation. The data thus suggest the presence of preferential cognitive processing between and within posterior and frontal cortical regions. http://precedings.nature.com/documents/1673/version/1 oai:nature.com:10.1038/npre.2008.1673.1 http://dx.doi.org/10.1038/npre.2008.1673.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1674.1 2008-03-11T10:30:11Z microbiology bioinformatics

_M. tuberculosis_ interactome analysis unravels potential pathways to drug resistance 2008-03-11T04:18:35Z Karthik Raman Nagasuma Chandra Microbiology Bioinformatics Drug resistance is a major problem for combating tuberculosis. Lack of understanding of how resistance emerges in bacteria upon drug treatment limits our ability to counter resistance. By analysis of the _Mycobacterium tuberculosis_ interactome network, along with drug-induced expression data from literature, we show possible pathways for the emergence of drug resistance. To a curated set of resistance related proteins, we have identified sets of high propensity paths from different drug targets. Many top paths were upregulated upon exposure to anti-tubercular drugs. Different targets appear to have different propensities for the four resistance mechanisms. Knowledge of important proteins in such pathways enables identification of appropriate _'co-targets'_, which when simultaneously inhibited with the intended target, is likely to help in combating drug resistance. RecA, Rv0823c, Rv0892 and DnaE1 were the best examples of co-targets for combating tuberculosis. This approach is also inherently generic, likely to significantly impact drug discovery. http://precedings.nature.com/documents/1674/version/1 oai:nature.com:10101/npre.2008.1674.1 http://hdl.handle.net/10101/npre.2008.1674.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1676.1 2008-03-12T21:06:37Z ecology

Ancient fossil specimens of extinct species are genetically more distant to an outgroup than extant sister species are 2008-03-11T18:16:51Z Shi Huang Ecology There exists a remarkable correlation between genetic distance and time of species divergence as inferred from fossil records. This observation has provoked the molecular clock hypothesis. However, data inconsistent with the hypothesis have steadily accumulated in recent years from studies on extant organisms. Here the published DNA and protein sequences from ancient fossil specimens were examined to see if they would support the molecular clock hypothesis. The hypothesis predicts that ancient specimens cannot be genetically more distant to an outgroup than extant sister species are. Also, two distinct ancient specimens cannot be genetically more distant than their extant sister species are. The findings here did not support these predictions. Neanderthals are more distant to chimpanzees and gorillas than modern humans are. Dinosaurs are more distant to frogs than extant birds are. Mastodons are more distant to opossums than other placental mammals are. The genetic distance between dinosaurs and mastodons is greater than that between extant birds and mammals. Therefore, while the molecular clock hypothesis is consistent with some data from extant organisms, it has yet to find support from ancient fossils. http://precedings.nature.com/documents/1676/version/1 oai:nature.com:10101/npre.2008.1676.1 http://hdl.handle.net/10101/npre.2008.1676.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1679.1 2008-03-14T16:15:33Z neuroscience

Chronobiology of Epilepsy 2008-03-11T23:22:25Z Sachin S. Talathi Dong-Uk Hwang William Ditto Mark Spano Hector Sepulveda Tom Mareci Paul Carney Neuroscience A fine balance between neuronal excitation and inhibition governs the physiological state of the brain. It has been hypothesized that when this balance is lost as a result of excessive excitation or reduced inhibition, pathological states such as epilepsy emerge. Decades of investigation have shown this to be true in vitro. However, in vivo evidence of the emerging imbalance during the "latent period" between the initiation of injury and the expression of the first spontaneous behavioral seizure has not been demonstrated. Here, we provide the first demonstration of this emerging imbalance between excitation and inhibition in vivo by employing long term, high temporal resolution, and continuous local field recordings from microelectrode arrays implanted in an animal model of limbic epilepsy. We were able to track both the inhibitory and excitatory postsynaptic field activity during the entire latent period, from the time of injury to the occurrence of the first spontaneous epileptic seizure. During this latent period we observe a sustained increase in the firing rate of the excitatory postsynaptic field activity, paired with a subsequent decrease in the firing rate of the inhibitory postsynaptic field activity within the CA1 region of the hippocampus. Firing rates of both excitatory and inhibitory CA1 field activities followed a circadian- like rhythm, which is locked near in-phase in controls and near anti-phase during the latent period. We think that these observed changes are implicated in the occurrence of spontaneous seizure onset following injury. http://precedings.nature.com/documents/1679/version/1 oai:nature.com:10101/npre.2008.1679.1 http://hdl.handle.net/10101/npre.2008.1679.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1684.1 2008-03-13T12:46:38Z bioinformatics plant-biology

GabiPD: Gabi Primary Database - a plant integrative ‘omics’ database in GABI-FUTURE 2008-03-13T12:13:12Z Diego Mauricio Riaño-Pachón Axel Nagel Robert Wagner Elke Weber Birgit Kersten Bioinformatics Plant Biology GabiPD ("http://gabi.rzpd.de":http://gabi.rzpd.de) was established within GABI-I and further developed in GABI-II and constitutes a repository and analysis platform for a wide array of heterogeneous data arising from high throughput experiments developed by members of the GABI/WPG community. Currently, data from different fronts (genomics, transcriptomics, proteomics, metabolomics) are incorporated in GabiPD, representing 14 different biological species. Last year GabiPD moved to the Max Planck Institute of Molecular Plant Physiology. In the progressing GABI-FUTURE phase, the GabiPD team has been creating a more integrative data view, expanding the tools and information provided by our well-known GreenCards. Links to different species-specific (_Arabidopsis thaliana_ so far) GABI-resources (e.g., Aramemnon, GABI-KAT) as well as external resources (e.g., ProMEX) are being added or updated. All data types (e.g., protein spots, clones) in GabiPD are pointing to the central Gene’s GreenCard, where gene information is retrieved from genome annotation projects or large UniGene sets provided by NCBI. Moreover, the GabiPD team will perform new types of data computations, like analysis of conserved domains in protein sequences. http://precedings.nature.com/documents/1684/version/1 oai:nature.com:10.1038/npre.2008.1684.1 http://dx.doi.org/10.1038/npre.2008.1684.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1685.1 2008-03-13T20:30:09Z biotechnology chemistry bioinformatics

Sequence-specific Solution Structures of the Four Isosequential Pairs of Single-stranded DNAs and RNAs 2008-03-13T13:17:26Z Subhrangsu Chatterjee Wimal Pathmasiri Jyoti Chattopadhyaya Biotechnology Chemistry Bioinformatics The role of the sequence-context in the self-organization of four single-stranded (ss) isosequential pairs of DNAs (1 – 4) and RNAs (5 – 8), [d/r-(5'C^1^A^2^X^3^G^4^Y^5^A^6^C^7^): X^3^ = A or C, Y^5^ = A or C; sequence variations: 2^2^ = 4], has been elucidated by NMR-constrained Molecular Dynamics (MD) simulations (2 ns). Following sequence-specific observations have been made from the solution NMR and the NMR constrained MD simulation study: (i) Analysis of the NOESY footprints, mainly (H8/H6)~n~ to (H1' and H3')~n-1~ contacts, of ssDNAs (1 - 4) and ssRNAs (5 – 8) in the aqueous medium have shown that all ssDNAs (1 - 4) and ssRNAs (5 - 8) adopt right handed stacked helical structures in the NMR time scale. (ii) Intra-residual cross-peak intensities for the H(8/6)~n-~ H(1'/2'/2''/H3')~n~ contacts in ssDNAs and ssRNAs are stronger at the 3'-ends in comparison with those at the 5'-ends, suggesting that the dynamics of the nucleobases at the 3'-end are more restricted, whereas those at the 5'-end are more flexible. (iii) This relative NMR found mobility is consistent with the final RMSd calculations of the final NMR-MD structures of ssDNAs and ssRNAs. They show that the 5'-end nucleobases have higher RMSd values compared to those at the 3'-end, except for the sequence d/r(5'C^1^A^2^A^3^G^4^A^5^A^6^C^7^). (iv) Relative nOe intensities of inter-residual H(8/6)~n~ - H(1')~n-1~ and H(8/6)~n~ - H(3')~n-1~ contacts, as well as NMR observed fluctuations in the sugar conformations, for ssDNAs (1 – 4) and ssRNAs (5 – 8) show that no ssDNA or ssRNA adopts either a typical B-type DNA or A-type RNA form. (v) In the final NMR-MD structures all the [H8/6N~(n)~ -- H1'N~(n-1)~/ H3'N~(n-1)~, N = A, G, C] distances in different isosequential pairs of ssDNA (1 – 4) and ssRNA (5 – 8) change depending upon the sequence context of the single-stranded nucleic acids. Both in the deoxy and ribo series, it is the purine-rich sequences [d/r-(5'C^1^A^2^A^3^G^4^A^5^A^6^C^7^) which form the most stable self-organized right-handed helical structures because of the favorable purine-purine stacking interactions. (vi) Stacking pattern at each of the dinucleotide steps show that the base-base nearest neighbor stacking interactions depend solely upon the sequence contexts of the respective ssDNAs (1 – 4) and ssRNAs (5 – 8). See pages 47 – 145 for Supplementary Information for detailed spectroscopic data. http://precedings.nature.com/documents/1685/version/1 oai:nature.com:10101/npre.2008.1685.1 http://hdl.handle.net/10101/npre.2008.1685.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1686.1 2008-03-14T13:32:50Z neuroscience

Representing an Object by Interchanging What with Where 2008-03-14T09:00:22Z Jong-Hoon Ahn Yillbyung Lee Neuroscience Exploring representations is a fundamental step towards understanding vision. The visual system carries two types of information along separate pathways: One is about what it is and the other is about where it is. Initially, the what is represented by a pattern of activity that is distributed across millions of photoreceptors, whereas the where is 'implicitly' given as their retinotopic positions. Many computational theories of object recognition rely on such pixel-based representations, but they are insufficient to learn spatial information such as position and size due to the implicit encoding of the where information. 
Here we try transforming a retinal image of an object into its internal image via interchanging the what with the where, which means that patterns of intensity in internal image describe the spatial information rather than the object information. To be concrete, the retinal image of an object is deformed and turned over into a negative image, in which light areas appear dark and vice versa, and the object's spatial information is quantified with levels of intensity on borders of that image. 
Interestingly, the inner part excluding the borders of the internal image shows the position and scale invariance. In order to further understand how the internal image associates the what and where, we examined the internal image of a face which moves or is scaled on the retina. As a result, we found that the internal images form a linear vector space under the object translation and scaling. 
In conclusion, these results show that the what-where interchangeability might play an important role for organizing those two into internal representation of brain. http://precedings.nature.com/documents/1686/version/1 oai:nature.com:10101/npre.2008.1686.1 http://hdl.handle.net/10101/npre.2008.1686.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1687.1 2008-03-18T12:38:18Z biotechnology

_In vivo_ photoacoustic molecular imaging with simultaneous multiple selective targeting using antibody-conjugated gold nanorods 2008-03-15T07:56:59Z Pai-Chi Li Dar-Bin Shieh Churng-Ren Wang Chen-Wei Wei Chao-Kang Liao Ann-Ann Ding Ya-Na Wu Carolina Poe Suwen Jhan Biotechnology The use of gold nanorods for photoacoustic molecular imaging in vivo with simultaneous multiple selective targeting is reported. The extravasation of multiple molecular probes is demonstrated, and used to probe molecular information of cancer cells. This technique allows molecular profiles representing tumor characteristics to be obtained and a heterogeneous population of cancer cells in a lesion to be determined. The results also show that the image contrast can be enhanced by using a mixture of different molecular probes. In this study, HER2, EGFR, and CXCR4 were chosen as the primary target molecules for examining two types of cancer cells, OECM1 and Cal27. OECM1 cells overexpressed HER2 but exhibited a low expression of EGFR, while Cal27 cells showed the opposite expression profile. Single and double targeting resulted in signal enhancements of up to 3 dB and up to 5 dB, respectively, and hence has potential in improving cancer diagnoses. http://precedings.nature.com/documents/1687/version/1 oai:nature.com:10101/npre.2008.1687.1 http://hdl.handle.net/10101/npre.2008.1687.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1688.1 2008-03-17T21:11:24Z neuroscience pharmacology

Systemic similarity analysis of compatibility drug-induced multiple pathway patterns _in vivo_ 2008-03-15T08:12:14Z Zhong Wang Zhan-jun Zhang Yi Wang Yiyu Cheng Weida Tong Yongyan Wang Neuroscience Pharmacology A major challenge in post-genomic research is to understand how physiological and pathological phenotypes arise from the networks of expressed genes and to develop powerful tools for translating the information exchanged between gene and the organ system networks. Although different expression modules may contribute independently to different phenotypes, it is difficult to interpret microarray experimental results at the level of single gene associations. The global effects and response pathways of small molecules in cells have been investigated, but the quantitative details of the activation mechanisms of multiple pathways _in vivo_ are not well understood. Similar response networks indicate similar modes of action, and gene networks may appear to be similar despite differences in the behaviour of individual gene groups. Here we establish the method for assessing global effect spectra of the complex signaling forms using Global Similarity Index (GSI) in cosines vector included angle. Our approach provides quantitative multidimensional measures of genes expression profile based on drug-dependent phenotypic alteration _in vivo_. These results make a starting point for identifying relationships between GSI at the molecular level and a step toward phenotypic outcomes at a system level to predict action of unknown compounds and any combination therapy. http://precedings.nature.com/documents/1688/version/1 oai:nature.com:10101/npre.2008.1688.1 http://hdl.handle.net/10101/npre.2008.1688.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1606.3 2008-03-19T19:34:10Z ecology

Differences of morphological and ecological characters among lineages of Chilean Rhinocryptidae in relation an sister lineage of Furnariidae. 2008-03-18T01:38:09Z Alejandro Correa Rueda Jorge Mpodozis Michel Sallaberry Ecology Eight species of Rhinocryptidae are recognized from Chile. Moreover, morphological, ecological and behavioral differences among two lineages of Scytalopus and two species of Pteroptochos are unclear. According to our results, there are no decisive criteria differentiating among subspecific sister taxa of Scelorchilus albicollis, S.rubecula and Pteroptochos megapodius. Here we discuss the speciation of the chilean Rhinocryptidae based in their behaviour and we carried out an integrated analysis with specie outgroup Cinclodes oustaleti (Furnariidae). We propose a new methodology based on ecological and behavioural patterns in order to understand the concept of speciation in this group of birds.

Key words: Rhynocriptidae, Pteroptochos, Scytalopus, Scelorchilus, Eugralla, Furnariidae, behaviour, adaptation, evolutionary clues.


 http://precedings.nature.com/documents/1606/version/3 oai:nature.com:10.1038/npre.2008.1606.3 http://dx.doi.org/10.1038/npre.2008.1606.3 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1597.2 2008-03-19T18:01:22Z ecology evolutionary-biology

Speciation of chilean Rhinocryptidae (Avian) based on their behaviour 2008-03-18T14:45:32Z Alejandro Correa Rueda Jorge Mpodozis Ecology Evolutionary Biology The current classification of the chilean representatives of the passerine family Rhinocryptidae includes eight species. Three of them contain subspecies that don’t exhibit clear differences. Moreover, differences among two lineages of _Scytalopus_ genera and two species of _Pteroptochos_ are very scarce. We propose a new methodology based on ecological and behavioural patterns in order to understand the concept of speciation in this group of birds. According to our results, we postulate that there is not a cut criteria to establish differences among three sister lineages of current classification. This way the methodology developed by us does not allow to establish divergence for a given common ancestor. Our methodology allows to establish comparison among previously determined phylogenetic lineages. Our results show how when integrating behaviour and ecological terms as biological traits next to morphological characters of the plumage, it allows us to conclude that there is decrease of the distances among sister lineages in the cluster tree. http://precedings.nature.com/documents/1597/version/2 oai:nature.com:10.1038/npre.2008.1597.2 http://dx.doi.org/10.1038/npre.2008.1597.2 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1690.1 2008-03-18T17:38:40Z ecology

Less is more: rarity trumps quality in luxury markets 2008-03-18T15:52:11Z Agnes Gault Yves Meinard Franck Courchamp Ecology The international market for luxury goods has almost doubled since 1990, with a worldwide increase of 10% annually. This trade is fuelled by a great deal of legally and illegally exploited wildlife species, putting enormous pressure on many of them, with potentially irreversible consequences. The dramatic decline of sturgeon populations exploited for their caviar, is a good example: all 27 species are threatened and the most coveted are on the verge of extinction. We aim to identify the mechanism responsible for the continued overexploitation of sturgeon species, despite caviar's ever-increasing price and the imminent loss of these species. Here, we demonstrate consumer preference for rarity over intrinsic quality: customers tasting two caviar samples more often chose the one they thought was rare, although both were identical. In a game theory model, we demonstrate that the most rational behaviour is to rush to consume rare species, even though this precipitates their extinction. We conclude that the human predisposition to place exaggerated value on rarity probably drives the entire market for luxury goods from reptile skins to exotic woods. Our findings suggest that allowing low levels of legal trade will exacerbate the arbitrary value of rare species and thereby stimulate demand. Only a total ban on trade from the wild (with very strict controls) combined with strong support for farmed equivalents will protect rare species. http://precedings.nature.com/documents/1690/version/1 oai:nature.com:10101/npre.2008.1690.1 http://hdl.handle.net/10101/npre.2008.1690.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1694.1 2008-03-20T14:26:14Z neuroscience

Investigating the frontoparietal network in mental calculation in primary school children - An fMRI study 2008-03-19T14:02:39Z Katrien Mondt Danielle Balériaux Thierry Metens Philippe Paquier Piet Van de Craen Vincent Denolin Neuroscience The frontoparietal network activated during calculation processing is investigated in a pediatric population. Subjects assessed correctness of two and three operand equations. Besides traditional frontoparietal activation, clear activation of sites associated with error processing was observed. http://precedings.nature.com/documents/1694/version/1 oai:nature.com:10101/npre.2008.1694.1 http://hdl.handle.net/10101/npre.2008.1694.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1695.1 2008-03-22T04:48:44Z development

Pro-social motive promotes early understanding of false belief 2008-03-20T06:48:48Z Tomoko Matsui Yui Miura Developmental Biology Ever since Premack & Woodruff's classic article^1^, which introduced the term "theory of mind", researchers have claimed that strategic deception is the most natural behavioural consequence of understanding false belief. Here we challenge that claim, and provide evidence for the first time that the earliest manifestation of false belief understanding in human development is found in young children's emerging pro-social behaviours. In a modified false belief task, children were asked either to choose one protagonist they should help to find the object (the pro-social context), or to choose one they need to deceive so that none of the protagonists can find the object (the competitive context). The results show that the pro-social motive, but not the competitive motive, boosts early false belief understanding. This is most clearly contrasted with findings that apes, our closest living relatives, are capable of intentionally manipulating others by concealing information only under competitive motives, not under cooperative alternatives. Thus, the current findings are the strongest to date that sophisticated understanding of others' belief in humans has its unique origin, separate from the primate origin at some point in recent evolution, when cooperative and communicative motives played an essential role for their survival. http://precedings.nature.com/documents/1695/version/1 oai:nature.com:10101/npre.2008.1695.1 http://hdl.handle.net/10101/npre.2008.1695.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1697.1 2008-03-20T19:50:07Z biotechnology chemistry microbiology

A Bacterial Enzyme Catalyzing Double Reduction of a β,δ-Diketo Ester with Unprecedented Stereoselectivity 2008-03-20T07:48:06Z Xuri Wu Nan Liu Yunmian He Yijun Chen Biotechnology Chemistry Microbiology Various ketoreductases exclusively participate in all common biological events, and they are a class of important biocatalysts for the production of chiral alcohols. While many types of ketoreductase have been extensively studied and their functions, properties and utilities have been well known, the capability of stereoselectively reducing two carbonyl groups in the same diketohexanoate ester molecule to form a dihydroxy product by a single ketoreductase has not been evidently characterized. Here we show that a unique and novel enzyme, diketoreductase, was cloned from Acinetobacter baylyi, heterogeneously expressed in _Escherichia coli_ and purified to homogeneity. The diketoreductase is up to 78% homologous to bacterial 3-hydroxyacyl coenzyme-A reductases. However, recombinant diketoreductase does not reduce HMG-CoA, showing that the inference of function of enzymes like the diketoreductase based on sequence homology may be in error. The enzyme directly converts a β,δ-diketo ester to the corresponding dihydroxy ester. More remarkably, our results demonstrate that the recombinant enzyme possesses unprecedented stereoselectivity with both diastereomeric and enantiomeric excesses of greater than 99%. This new enzyme is of immediate value in developing a practical biocatalytic route to the side chains of statin drugs, such as Lipitor®. http://precedings.nature.com/documents/1697/version/1 oai:nature.com:10101/npre.2008.1697.1 http://hdl.handle.net/10101/npre.2008.1697.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1700.1 2008-03-20T21:00:20Z bioinformatics

A review of journal policies for sharing research data 2008-03-20T16:05:38Z Heather A. Piwowar Wendy W. Chapman Bioinformatics *Background:* Sharing data is a tenet of science, yet commonplace in only a few subdisciplines. Recognizing that a data sharing culture is unlikely to be achieved without policy guidance, some funders and journals have begun to request and require that investigators share their primary datasets with other researchers. The purpose of this study is to understand the current state of data sharing policies within journals, the features of journals which are associated with the strength of their data sharing policies, and whether the strength of data sharing policies impact the observed prevalence of data sharing. 

*Methods:* We investigated these relationships with respect to gene expression microarray data in the journals that most often publish studies about this type of data. We measured data sharing prevalence as the proportion of papers with submission links from NCBI's Gene Expression Omnibus (GEO) database. We conducted univariate and linear multivariate regressions to understand the relationship between the strength of data sharing policy and journal impact factor, journal subdiscipline, journal publisher (academic societies vs. commercial), and publishing model (open vs. closed access).

*Results:* Of the 70 journal policies, 18 (26%) made no mention of sharing publication-related data within their Instruction to Author statements. Of the 42 (60%) policies with a data sharing policy applicable to microarrays, we classified 18 (26% of 70) as moderately strong and 24 (34% of 70) as strong.
Existence of a data sharing policy was associated with the type of journal publisher: half of all commercial publishers had a policy compared to 82% of journals published by academic society. All four of the open-access journals had a data sharing policy. Policy strength was associated with impact factor: the journals with no data sharing policy, a weak policy, and a strong policy had respective median impact factors of 3.6, 4.5, and 6.0. Policy strength was positively associated with measured data sharing submission into the GEO database: the journals with no data sharing policy, a weak policy, and a strong policy had median data sharing prevalence of 11%, 19%, and 29% respectively.

*Conclusion:* This review and analysis begins to quantify the relationship between journal policies and data sharing outcomes and thereby contributes to assessing the incentives and initiatives designed to facilitate widespread, responsible, effective data sharing. 

 http://precedings.nature.com/documents/1700/version/1 oai:nature.com:10101/npre.2008.1700.1 http://hdl.handle.net/10101/npre.2008.1700.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1701.1 2008-03-20T17:08:03Z bioinformatics

Prevalence and Patterns of Microarray Data Sharing 2008-03-20T16:21:02Z Heather A. Piwowar Wendy W. Chapman Bioinformatics Sharing research data is a cornerstone of science. Although many tools and policies exist to encourage data sharing, the prevalence with which datasets are shared is not well understood. We report our preliminary results on patterns of sharing microarray data in public databases.

The most comprehensive method for measuring occurrences of public data sharing is manual curation of research reports, since data sharing plans are usually communicated in free text within the body of an article. Our early findings from manual curation of 100 papers suggest that 30% of investigators publicly share their full microarray datasets. Of these, 70% of the datasets are deposited at NCBI's Gene Expression Omnibus (GEO) database, 20% at EBI's ArrayExpress, and 10% in smaller databases or lab or publisher websites.

Next, we supplemented this manual process with a rough automated estimate of data sharing prevalence. Using PubMed, we identified research articles with MeSH terms for both "Gene Expression Profiling" and "Oligonucleotide Array Sequence Analysis" and published in 2006. We then searched GEO and ArrayExpress for links to these PubMed IDs to determine which of the articles had been credited as an originating data source.

Of the 2503 articles, 440 (18%) articles had links from either GEO or ArrayExpress. Of these 440 articles, 70% had links from GEO and 30% from ArrayExpress, with an overlapping 12% from both GEO and ArrayExpress.

Interestingly, studies with free full text at PubMed were twice (Odds Ratio=2.1; 95% confidence interval: [1.7 to 2.5]) as likely to be linked as a data source within GEO or ArrayExpress than those without free full text. Studies with human data were less likely to have a link (OR=0.8 [0.6 to 0.9]) than studies with only non-human data. The proportion of articles with a link within these two databases has increased over time: the odds of a data-source link for studies was 2.5 [2.0 to 3.1] times greater for studies published in 2006 than 2002.

As might be expected, studies with the fewest funding sources had the fewest data-sharing links: only 28 (6%) of the 433 studies with no funding source were listed within GEO or ArrayExpress. In contrast, studies funded by the NIH, the US government, or a non-US government source had data-sharing links in 282 of 1556 cases (18%), while studies funded by two or more of these mechanisms were listed in the databases in 130 out of 514 cases (25%).

In summary, our initial manual approach for identifying studies which shared their data was comprehensive but time-consuming; natural language processing techniques could be helpful. Our subsequent automated approach yielded conservative estimates for total data sharing prevalence, nonetheless revealing several promising hypotheses for data sharing behavior

We hope these preliminary results will inspire additional investigations into data sharing behavior, and in turn the development of effective policies and tools to facilitate this important aspect of scientific research. http://precedings.nature.com/documents/1701/version/1 oai:nature.com:10.1038/npre.2008.1701.1 http://dx.doi.org/10.1038/npre.2008.1701.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1702.1 2008-03-21T13:53:17Z molecular-cell-biology

Circadian rhythmic kinase CK2α phosphorylates BMAL1 to regulate the mammalian clock 2008-03-21T01:13:04Z Teruya Tamaru Jun Hirayama Yasushi Isojima Katsuya Nagai Shigemi Norioka Ken Takamatsu Paolo Sassone-Corsi Molecular Cell Biology Clock proteins govern circadian physiology and their function is regulated by a variety of signaling pathways. Here, we show that p45^PFK^, a previously reported circadian rhythmic kinase, corresponds to CK2[alpha]. Rhythmic phosphorylation of the core clock protein BMAL1 by CK2[alpha] occurs in the suprachiasmatic nuclei (SCN), the mammalian central pacemaker. Circadian BMAL1 phosphorylation controls its nucleocytoplasmic localization. Gene silencing for CK2[alpha] and BMAL1 mutagenesis of a highly conserved CK2 phosphorylation site (Ser 90) result in impaired BMAL1 accumulation in the nucleus and subsequent disruption of clock function. These findings reveal that circadian rhythmic kinase CK2 is an essential regulator of the mammalian circadian system. http://precedings.nature.com/documents/1702/version/1 oai:nature.com:10101/npre.2008.1702.1 http://hdl.handle.net/10101/npre.2008.1702.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1703.1 2008-03-26T15:35:23Z neuroscience

A Mathematical Model of a Neuron with Synapses based on Physiology 2008-03-21T02:15:36Z Xiaolin Zhang Neuroscience The neuron, when considered as a signal processing device, itsinputs are the frequency of pulses received at the synapses, and its output is the frequency of action potentials generated- in essence, a neuron is a pulse frequency signal processing device. In comparison, electrical devices use either digital or analog signals for communication or processing, and the mathematics behind these subjects is well understood. However, in regards to pulse frequency processing devices, there has not yet been a clear and persuasive mathematical model to describe the functions of neurons. It goes without saying that such a model is very important, not only for understanding neuron and neural system behavior, but also for undeveloped potential applications in industry. This paper proposes a method for obtaining the mathematical relationship between the input and output signals of a neuron based on physiological facts. The proposed method focuses on the currents across the postsynaptic membrane of each synapse, and the key is to recognize that the net charge across the whole membrane of a neuron over each action potential cycle must equal to zero. By analyzing the relationship between the input of a synapse and the currents across the postsynaptic membranes, a dynamic pulse frequency model of the neuron can be obtained. Here, we show that the transfer function of a neuron depends on the function of thepostsynaptic current of each synapse in resting state, which can be found by detecting the postsynaptic current when a pulse is received at the synapse. The transfer function of a typical neuron generally includes addition and subtraction of feedthrough terms and/or first order lag functions. To focus on the most basic characteristics of a neuron, accommodation, adaptation, learning, etc. are not discussed in this paper. http://precedings.nature.com/documents/1703/version/1 oai:nature.com:10101/npre.2008.1703.1 http://hdl.handle.net/10101/npre.2008.1703.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1706.1 2008-03-21T16:43:49Z earth-and-environment

Icebergs boost phytoplankton growth in the Southern Ocean 2008-03-21T10:16:26Z Jill N. Schwarz Michael P. Schodlok Earth & Environment Icebergs which calve from the Antarctic ice shelves and drift in the Southern Ocean deliver fresh water, dust and minerogenic particles to the surface ocean along the iceberg's path. Each of these components may have an effect on growth conditions for phytoplankton, as might the mechanical effects of the iceberg keel disturbing the water. Although anecdotal evidence and small-scale surveys suggest that drifting icebergs increase local primary production, no large-scale studies have reported on this possibility in detail. A combination of satellite and automated iceberg tracking data presented here shows that the probability of increased surface phytoplankton biomass was two-fold higher in the wake of a tracked iceberg compared to background biomass fluctuations. Only during the month of February were the effects of icebergs on surface biomass likely to be negative. These results confirm icebergs as a factor affecting phytoplankton in the Southern Ocean and highlight the need for detailed process studies so that responses to future changes in the Antarctic ice sheets may be predicted. http://precedings.nature.com/documents/1706/version/1 oai:nature.com:10101/npre.2008.1706.1 http://hdl.handle.net/10101/npre.2008.1706.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1708.1 2008-03-24T15:33:35Z molecular-cell-biology evolutionary-biology

"Ribopepzymes" are probably a link from ribozymes to protein enzymes 2008-03-21T12:37:28Z Yongjie Sheng Dazhi Jiang Zhen Zeng Feng Pan Jin Zhang Molecular Cell Biology Evolutionary Biology The evolutionary relationship between RNA- and protein-based biocatalysts was key to the evolution of living systems. This relationship is thought to have depended upon the transfer of both genetic information and catalytic function in living systems. We investigated whether ribozymes could transfer genetic information and catalytic function at the chemical level. We identified a family of peptides encoded by ribozymes: 13-residue peptide encoded by the hammerhead ribozyme, a 19-residue peptide encoded by the genomic hepatitis delta virus (HDV+) ribozyme, a 25-residue peptide encoded by the antigenomic HDV (HDV-) ribozyme, a 15-residue peptide encoded by the smallest trans-acting genomic HDV (SHDV) ribozyme, and a 22-residue peptide encoded by an open reading frame (ORF) of RNase P. We show that all these peptides possess the ability to cleave single-stranded RNA substrates. Furthermore, we expressed a 56-residue peptide encoded by an intact ORF (616-783) of the VS ribozyme, and found that it has single-stranded RNA cleavage activity as well. Because these catalytic peptides arise from a ribozyme-based code and their catalytic activity is ribonuclease-like, we have designated these peptides as "ribopepzymes". Ribopepzymes could be a link from ribozymes to protein enzymes in the early origin and evolution of enzymes. They also may provide a basis for designed, divergent evolution of enzyme function. http://precedings.nature.com/documents/1708/version/1 oai:nature.com:10101/npre.2008.1708.1 http://hdl.handle.net/10101/npre.2008.1708.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1709.1 2008-03-27T21:05:50Z genetics microbiology molecular-cell-biology

Preincision Processing of Cyclobutane Pyrimidine Dimers in Escherichia coli 2008-03-21T19:15:48Z Sunirmal Paul Mitsumasa Hashimoto Opinder Bhanot Yoke Kow Moon-shong Tang Genetics & Genomics Microbiology Molecular Cell Biology In both prokaryotes and eukaryotes cyclobutane pyrimidine dimers (CPD) formed by UV-irradiation are repaired mainly by the nucleotide excision repair (NER) pathway. Evidence has been presented that CPDs are repaired more rapidly and efficiently in vivo than when using purified NER components in vitro, and raises the possibility that CPD can be processed at the preincision stage before being removed by NER pathway. We investigated this hypothesis in E. coli cells and found that the phosphodiester bonds in CPDs are indeed incised (for the sake of simplicity we term this result as CPD*) in a time-dependent fashion in NER-proficient cells. This CPD preincision processing also occurs in NER-deficient uvrB- and uvrC-, but not in uvrA-mutant cells, and in endonuclease V (nfi) mutant cells. Introduction of the nfi mutation into wild type or uvrB-mutant cells results in disablement of CPD to CPD* conversion and enhances UV sensitization to the level of uvrA-mutant cells. We found that in a reconstituted in vitro system, that purified UvrA and Nfi are necessary but not sufficient to convert CPD to CPD*. A UvrC homologous protein, Cho, is also needed for this conversion. In addition, we found that Nfi does not bind to UV-irradiated DNA, suggesting that UvrA and Cho proteins may function as matchmakers for Nfi-CPD binding, which consequently results in the conversion of CPD to CPD*. We further demonstrated that CPD*, but not CPD, can allow efficient translesion bypass synthesis with accuracy. We thus have elucidated a new CPD preincision processing mechanism and genes involved in this process. The biological significance of these findings is discussed elsewhere (another manuscript in preparation). http://precedings.nature.com/documents/1709/version/1 oai:nature.com:10101/npre.2008.1709.1 http://hdl.handle.net/10101/npre.2008.1709.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1710.1 2008-03-24T15:08:10Z evolutionary-biology

Genetic similarity promotes evolution of cooperation under lethal intergroup competition 2008-03-21T22:42:35Z Oleg Smirnov John Orbell Evolutionary Biology Altruism (helping others at a cost to oneself) may evolve via group selection if the cost of altruism to the individual is compensated for by growth differences among groups when (1) there is high genetic variation among members of different groups; (2) more altruistic groups grow faster and (3) between-group migration is low. Nevertheless, group selection may not fully explain the actual evolution of helping behaviour if between-group migration was sufficiently common to have reduced between-group genetic variance. Lethal intergroup competition, which amplifies such growth differences between groups, appears to have been frequent in humans'; ancestral environments and could bear importantly on the evolution of altruism. Here we show that between-group migration and resulting genetic similarity can promote the evolution of costly helping behavior in the context of lethal intergroup conflict, albeit by selection at the individual level and not by group selection. The standard group selection models do not capture such basic elements of lethal intergroup competition as the possibility of an individual's altruism being critical to the group's success when that possibility is inversely proportional to genetic variation among members of the competing groups. http://precedings.nature.com/documents/1710/version/1 oai:nature.com:10101/npre.2008.1710.1 http://hdl.handle.net/10101/npre.2008.1710.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1713.1 2008-03-24T16:23:42Z ecology genetics microbiology

Selfish and Altruistic Bacterial Populations Maximize Fitness Under Stress by Local Segregation 2008-03-23T23:26:02Z Juan Keymer Peter Galajda Juliana Malinverni Roberto Kolter Guillaume Lambert David Liao Robert Austin Ecology Genetics & Genomics Microbiology Landscapes in ecology have a profound influence on the adaption and evolution of competing populations for resources. We are interested in how altruistic populations survive in the presence of selfish individuals in a non-stirred, closed and complex nutrient landscape. Well-stirred (landscape-free) but closed environments have a depressing future when selfish individuals arise in a population, a fate known as the tragedy of the Commons. Over-exploitation of a well-stirred communal habitat by selfish individuals which do not follow rules of communal self-regulation ends up in the elimination (extinction) of both the original altruistic inhabitants and the selfish population. In the context of bacterial population, the Commons tragedy that occurs is the consumption of limited resources by the individuals, resulting in metabolic stressing of the bacteria and growth advantages to be gained by defection from a ``social contract" of altruistic cooperation. There is no avoidance of this tragedy and the collapse of an original altruistic wild-type population by an emergent selfish population in a well-stirred but closed environment is inevitable. However, there is a fundamental difference between resource exploitation in a well-stirred homogenous commons and in a heterogenous landscape of nutrients which is not stirred. We show here using a non-stirred nanofabricated habitat landscape that altruists and selfish bacteria can in fact coexist, that they can maintain phenotype diversity and avoid the tragedy of the Commons. This emergent spatial segregation of competing populations under stress greatly changes, we believe, our perception of the true sophistication of bacterial response to stress and competition, and has broad implications for the adaptive strategies of higher organisms under stress in complex environments. http://precedings.nature.com/documents/1713/version/1 oai:nature.com:10101/npre.2008.1713.1 http://hdl.handle.net/10101/npre.2008.1713.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1714.1 2008-03-24T20:47:07Z biotechnology

Diamond nanowires, a new approach towards next generation electrochemical gene sensor platforms 2008-03-24T08:13:29Z Nianjun Yang Hiroshi Uetsuka Jiuhong Yu Eiji Osawa Norio Tokuda Christoph Nebel Biotechnology A novel bio-sensing platform is introduced by combination of a) geometrically controlled DNA bonding using vertically aligned diamond nano-wires and b) the superior electrochemical sensing properties of diamond as transducer material. Ultra-hard vertically aligned diamond nanowires are electrochemically modified to bond phenyl linker-molecules to their tips which provide mesospacing for DNA molecules on the transducer. The nano-wires are generated by reactive ion etching of metallically boron doped atomically smooth single crystalline CVD diamond. Surface properties are characterized by atomic force, scanning electron and scanning tunneling microcopy. Electro- and biochemical sensor properties are investigated using cyclic and differential pulse voltammetry as well as impedance spectroscopy with Fe(CN)63-/4- as redox mediators which reveal sensitivities of 2 pM on 3 mm2 sensor areas and superior DNA bonding stability over 30 hybridization/denaturation cycles. The fabrication of "all diamond" ultra-micro-electrode (UME) arrays and multi-gene sensors are discussed taking into account the unique properties of diamond. http://precedings.nature.com/documents/1714/version/1 oai:nature.com:10101/npre.2008.1714.1 http://hdl.handle.net/10101/npre.2008.1714.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1718.1 2008-03-25T14:56:49Z molecular-cell-biology

Myth about neuronal nitric oxide synthase in the sarcolemma of skeletal muscles 2008-03-25T12:45:32Z Igor Buchwalow Werner Boecker Molecular Cell Biology In skeletal muscles, neuronal NO synthase (nNOS, designated also as NOS1) was reported to be restricted to the sarcolemma. With the advent of modern powerful immunocytochemical techniques this commonly accepted view appears to be a delusion and has to be re-evaluated. http://precedings.nature.com/documents/1718/version/1 oai:nature.com:10101/npre.2008.1718.1 http://hdl.handle.net/10101/npre.2008.1718.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1719.1 2008-03-25T17:35:21Z ecology

Bumblebees under the midnight sun - Monitoring circadian rhythms of bumblebees under continuous daylight, using radio frequency identification (RFID) 2008-03-25T14:42:30Z Ralph J. Stelzer Lars Chittka Ecology Circadian rhythms enable organisms to anticipate and to prepare for predictable changes in their environment. Most previous studies on circadian rhythms focused on solitary animals. However, in social insects, the colony as a superorganism has a foraging rhythm aligned to the patterns of resource availability. Within this colony rhythm, the activity patterns of individuals are embedded. In temperate regions bumblebee foragers show strong circadian rhythms that adjust their foraging activity to the changing light conditions in the course of the day. But what about circadian foraging patterns under continuous daylight? One would assume that the colony as a whole extends its foraging activity over the whole 24 hours of a day under such light conditions to maximise colony growth. To answer this question four colonies of _Bombus terrestris terrestris_ have been set up in north-western Finland (Kilpisjärvi Biological Station, 270km north of the Arctic Circle) between 20/06/07 and 18/07/07. During that time period the sun is always above the horizon in that area. Each worker of each colony was fitted with a small RFID tag, allowing to continuously monitor the foraging activity of each individual worker for the whole duration of the experiment. Against the hypothesis the foragers still showed strong circadian rhythms and ceased their activity from about 0000h until about 0600h each day. http://precedings.nature.com/documents/1719/version/1 oai:nature.com:10.1038/npre.2008.1719.1 http://dx.doi.org/10.1038/npre.2008.1719.1 Nature Precedings Poster Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1720.1 2008-03-25T18:21:55Z neuroscience bioinformatics

Minimum Information about a Neuroscience Investigation (MINI) Electrophysiology 2008-03-25T15:24:49Z Frank Gibson Paul G. Overton Tom V. Smulders Simon R. Schultz Stephen J. Eglen Colin D. Ingram Stefano Panzeri Phil Bream Evelyne Sernagor Mark Cunningham Christopher Adams Christoph Echtermeyer Jennifer Simonotto Marcus Kaiser Daniel C. Swan Marty Fletcher Phillip Lord Neuroscience Bioinformatics This module represents the formalized opinion of the authors and the CARMEN consortium, which identifies the minimum information required to report the use of electrophysiology in a neuroscience study, for submission to the CARMEN system (www.carmen.org.uk).
 http://precedings.nature.com/documents/1720/version/1 oai:nature.com:10101/npre.2008.1720.1 http://hdl.handle.net/10101/npre.2008.1720.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1721.1 2008-03-25T21:14:35Z bioinformatics

Identifying Data Sharing in Biomedical Literature 2008-03-25T16:19:14Z Heather Piwowar Wendy W. Chapman Bioinformatics Many policies and projects now encourage investigators to share their raw research data with other scientists. Unfortunately, it is difficult to measure the effectiveness of these initiatives because data can be shared in such a variety of mechanisms and locations. We propose a novel approach to finding shared datasets: using NLP techniques to identify declarations of dataset sharing within the full text of primary research articles. Using regular expression patterns and machine learning algorithms on open access biomedical literature, our system was able to identify 61% of articles with shared datasets with 80% precision. A simpler version of our classifier achieved higher recall (86%), though lower precision (49%). We believe our results demonstrate the feasibility of this approach and hope to inspire further study of dataset retrieval techniques and policy evaluation.
 http://precedings.nature.com/documents/1721/version/1 oai:nature.com:10101/npre.2008.1721.1 http://hdl.handle.net/10101/npre.2008.1721.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1724.1 2008-03-27T19:04:52Z molecular-cell-biology

Pancreas islets in metabolic signaling - focus on the β-cell 2008-03-26T10:01:55Z Jakob Suckale Michele Solimena Molecular Cell Biology Taken together the Islets of Langerhans form a nutrient sensing network spread throughout the pancreas. They are tightly connected to the source organ - the intestine - and the target organs - liver, muscle, and fat cells. The expression of a unique set of proteins enables [beta] cells, the most frequent islet cell type, to detect elevated blood glucose levels and secrete insulin accordingly. Neighbouring [beta]-cells achieve tighter regulation of glucose-induced insulin secretion by coordination through cell surface proteins. They also adjust their secretory pathway capacity and flow to avoid being damaged. The immediate reaction of the [beta] cell to nutrients is regulated by translational mechanisms, while longer term adaptations involve changes in transcription. Glucose increases protein synthesis in the [beta] cell overall and especially that of some secretory proteins including insulin. This effect may be mediated through recognition of RNA motifs in the untranslated regions of those messengers. Failure of essential molecular components of the nutrient sensing system due to mutation or weakness paired with cellular stress can lead to dysfunctions, which on a larger scale manifest as diseases like diabetes mellitus. http://precedings.nature.com/documents/1724/version/1 oai:nature.com:10101/npre.2008.1724.1 http://hdl.handle.net/10101/npre.2008.1724.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1729.1 2008-03-27T15:03:25Z neuroscience

Colored filters improve exclusion of perceptual noise in visually symptomatic dyslexics 2008-03-27T12:41:29Z Nadia Northway Velitchko Manahilov William A. Simpson Neuroscience Dyslexic individuals have deficits in detecting visual stimuli embedded in high levels of perceptual noise. Here we show that visually symptomatic dyslexics, who otherwise had elevated contrast thresholds for discriminating symbols in visual noise, had thresholds similar to non-dyslexics when wearing colored filters. These findings provide evidence that colored filters, which minimize the visual distortions and discomfort of dyslexics when reading, improve dyslexics' noise exclusion to normal levels. http://precedings.nature.com/documents/1729/version/1 oai:nature.com:10101/npre.2008.1729.1 http://hdl.handle.net/10101/npre.2008.1729.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1732.1 2008-03-28T16:30:31Z cancer genetics

Requirement of RIZ1 for cancer prevention by methyl-balanced diet 2008-03-27T17:53:11Z Wenyun Zhou Sergio Alonso Daisaku Takai Shelly C. Lu Fumiichiro Yamamoto Manuel Perucho Shi Huang Cancer Genetics & Genomics The typical Western diet is not balanced in methyl nutrients that regulate the level of the methyl donor S-adenosylmethionine (SAM) and its derivative metabolite S-adenosylhomocysteine (SAH), which in turn may control the activity of certain methyltransferases. Feeding rodents with amino acid defined and methyl-imbalanced diet decreases hepatic SAM and causes liver cancers. RIZ1 (PRDM2 or KMT8) is a tumor suppressor and functions in transcriptional repression by methylating histone H3 lysine 9. Here we show that a methyl-balanced diet conferred additional survival benefits compared to a tumor-inducing methyl-imbalanced diet only in mice with wild type RIZ1 but not in mice deficient in RIZ1. While absence of RIZ1 was tumorigenic in mice fed the balanced diet, its presence did not prevent tumor formation in mice fed the imbalanced diet. Unlike most of its related enzymes, RIZ1 was upregulated by methyl-balanced diet. Methyl-balanced diet did not fully repress oncogenes such as c-Jun in the absence of RIZ1. The data identify RIZ1 as a critical target of methyl-balanced diet in cancer prevention. The molecular understanding of dietary carcinogenesis may help people make informed choices on diet, which may greatly reduce the incidence of cancer. http://precedings.nature.com/documents/1732/version/1 oai:nature.com:10101/npre.2008.1732.1 http://hdl.handle.net/10101/npre.2008.1732.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1733.1 2008-03-28T15:14:34Z ecology genetics bioinformatics

The genetic equidistance result of molecular evolution is independent of mutation rates 2008-03-27T20:18:15Z Shi Huang Ecology Genetics & Genomics Bioinformatics The genetic equidistance result shows that sister species are approximately equidistant to an outgroup as measured by DNA or protein dissimilarity. The equidistance result is the most direct evidence, and remains the only evidence, for the constant mutation rate interpretation of this result, known as the molecular clock. However, data independent of the equidistance result have steadily accumulated in recent years that often violate a constant mutation rate. Many have automatically inferred non-equidistance whenever a non-constant mutation rate was observed, based on the unproven assumption that the equidistance result is an outcome of constant mutation rate. Here it is shown that the equidistance result remains valid even when different species can be independently shown to have different mutation rates. A random sampling of 50 proteins shows that nearly all proteins display the equidistance result despite the fact that many proteins have non-constant mutation rates. Therefore, the genetic equidistance result does not necessarily mean a constant mutation rate. Observations of different mutation rates do not invalidate the genetic equidistance result. http://precedings.nature.com/documents/1733/version/1 oai:nature.com:10101/npre.2008.1733.1 http://hdl.handle.net/10101/npre.2008.1733.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1738.1 2008-03-28T20:58:23Z ecology genetics microbiology molecular-cell-biology

Bio-Communication of Bacteria and its Evolutionary Interrelations to Natural Genome Editing Competences of Viruses 2008-03-28T14:31:32Z Guenther Witzany Ecology Genetics & Genomics Microbiology Molecular Cell Biology Communicative competences enable bacteria to develop, organise and coordinate rich social life with a great variety of behavioral patterns even in which they organise themselves like multicellular organisms. They have existed for almost four billion years and still survive, being part of the most dramatic changes in evolutionary history such as DNA invention, cellular life, invention of nearly all protein types, partial constitution of eukaryotic cells, vertical colonisation of all eukaryotes, high adaptability through horizontal gene transfer and co-operative multispecies colonisation of all ecological niches. Recent research demonstrates that these bacterial competences derive from the aptitude of viruses for natural genome editing. 
	In contrast to a book which would be the appropriate space to outline in depth all communicative pathways inherent in bacterial life in this current article I want to give an overview for a broader readership over the great variety of bacterial bio-communication: In a first step I describe how they interpret and coordinate, what semiochemical vocabulary they share and which goals they try to reach. In a second stage I describe the main categories of sign-mediated interactions between bacterial and non-bacterial organisms, and between bacteria of the same or related species. In a third stage I will focus on the relationship between bacteria and their obligate settlers, i.e. viruses. We will see that bacteria are important hosts for multiviral colonisation and virally-determined order of nucleic acid sequences.

 http://precedings.nature.com/documents/1738/version/1 oai:nature.com:10101/npre.2008.1738.1 http://hdl.handle.net/10101/npre.2008.1738.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1739.1 2008-04-01T13:14:16Z chemistry earth-and-environment

Review of the Carbon Dioxide Splitting Patent Literature 2008-03-29T18:35:21Z Sierra Rayne Chemistry Earth & Environment Increasing concentrations of carbon dioxide in the atmosphere have stimulated significant global research and development efforts regarding the reduction in emissions from all point and non-point sources. In addition to technologies that do not use carbon feedstocks or which capture and "permanently" store carbon dioxide (i.e., sequestration), there is considerable worldwide interest for dissociating waste stream carbon dioxide molecules into their constituent carbon and oxygen atoms ("CO2 splitting") as a final "end-of-pipe" treatment option. This document presents a review of on-point issued and applied for patents in the field of carbon dioxide splitting. The findings suggest patents in this area appear to be subject to a higher standard because of the global importance of the carbon dioxide issue. Authorities may be hesitant, on policy grounds, to issue broad-ranging patents for carbon dioxide splitting in order to prevent a worldwide reluctance towards adopting feasible treatment methods because of the high patent licensing costs that may accrue. http://precedings.nature.com/documents/1739/version/1 oai:nature.com:10.1038/npre.2008.1739.1 http://dx.doi.org/10.1038/npre.2008.1739.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1740.1 2008-03-31T15:37:47Z chemistry earth-and-environment

Potential Impacts of Tailings and Tailings Cover Fertilization on Arsenic Mobility in Surface and Ground Waters 2008-03-29T21:27:58Z Sierra Rayne Kaya Forest Chemistry Earth & Environment A number of mining sites worldwide, particularly gold mines, have tailings management facilities (TMFs) that contain high levels of arsenic. Current closed mine site regulatory agencies tend to prefer revegetation of TMFs as part of the mandated reclamation activities. At many sites, often in polar regions, vegetation is difficult to establish either directly on the tailings or on the coarse-rock covers due to nutrient poor soils, phytotoxicity problems, and/or a less than optimum climate. Addition of phosphorus-based fertilizers to the tailings and/or cover material is commonly considered in order to promote the revegetation process and – ideally – allow the site owners to discharge their closure duties as rapidly as possible. However, due to the similar geochemistry of arsenic and phosphorus oxyanion species, this type of mine closure strategy may have unintended consequences regarding arsenic mobility on and off the site. This document reviews the current state-of-the-art regarding mobilization of arsenic by phosphate ions, and identifies relevant risks and opportunities of using this information to better manage closed mine sites. http://precedings.nature.com/documents/1740/version/1 oai:nature.com:10.1038/npre.2008.1740.1 http://dx.doi.org/10.1038/npre.2008.1740.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1741.1 2008-04-01T13:15:20Z chemistry earth-and-environment

Carbon Dioxide Splitting: A Summary of the Peer-Reviewed Scientific Literature 2008-03-29T23:09:29Z Sierra Rayne Chemistry Earth & Environment Increasing concentrations of carbon dioxide (CO2) in the atmosphere have stimulated significant global research and development efforts regarding the reduction in CO2 emissions from all point and non-point sources. In addition to technologies that do not use carbon feedstocks or which capture and "permanently" store CO2 (i.e., sequestration), there is considerable worldwide interest among the academic, industrial, and government communities regarding methods for dissociating waste stream carbon dioxide molecules into their constituent carbon and oxygen ("CO2 splitting") atoms as a final "end-of-pipe" treatment option. The splitting of carbon dioxide has also been actively discussed and researched in the space exploration and extraterrestrial colonization programs for several decades. This document summarizes the peer-reviewed open source scientific literature regarding carbon dioxide splitting. http://precedings.nature.com/documents/1741/version/1 oai:nature.com:10.1038/npre.2008.1741.1 http://dx.doi.org/10.1038/npre.2008.1741.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1742.1 2008-04-01T14:32:02Z genetics

Polymorphisms of the _ENPP1_ gene are not associated with type 2 diabetes or obesity in the Chinese Han population 2008-03-31T05:40:41Z Teng Zhao Di Zhang Yun Liu Daizhan Zhou Zhuo Chen Sheng Li Lan Yu Simin Liu Zuofeng Zhang Guoyin Feng Lin He He Xu Genetics & Genomics *Objective:* Type 2 Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia and with a major feature of insulin resistance. Genetic association studies have suggested that _ENPP1_ might play a potential role in susceptibility to type 2 diabetes and obesity. Our study aimed to examine the association between _ENPP1_ and type 2 diabetes and obesity.

*Design:* Association study between two SNPs, rs1044498 (K121Q) and rs7754561 of ENPP1 and diabetes and obesity in the Chinese Han population.

*Subjects:* 1912 unrelated patients (785 male and 1127 female with a mean age 63.8 ± 9 years), 236 IFG/IGT subjects (83 male and 153 female with a mean age 64 ± 9 years) and 2041 controls (635 male and 1406 female with a mean age 58 ± 9 years).
 
*Measurements:* Subjects were genotyped for two SNPs using TaqMan technology on an ABI7900 system and tested by regression analysis.

*Results:* By logistic regression analysis, rs1044498 (K121Q) and rs7754561 showed no statistical association with type 2 diabetes, obesity under additive, dominant and recessive models either before or after adjusting for sex and age. Haplotype analysis found a marginal association of haplotype C-G (p=0.05) which was reported in the previous study.

*Conclusion:* Our investigation did not replicated the positive association found previously and suggested that the polymorphisms of _ENPP1_ might not play a major role in the susceptibility to type 2 diabetes or obesity in the Chinese Han population. http://precedings.nature.com/documents/1742/version/1 oai:nature.com:10101/npre.2008.1742.1 http://hdl.handle.net/10101/npre.2008.1742.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1746.1 2008-04-01T20:13:29Z biotechnology bioinformatics

Coincidence between transcriptome analyses on different microarray platforms using a parametric framework 2008-04-01T05:41:42Z Tomokazu Konishi Fumikazu Konishi Shigeru Takasaki Kohei Inoue Kouji Nakayama Akihiko Konagaya Biotechnology Bioinformatics A parametric framework for the analysis of transcriptome data is demonstrated to yield coincident results when applied to data acquired using two different microarray platforms. Discrepancies among transcriptome studies are frequently reported, casting doubt on the reliability of collected data. The inconsistency among observations can be largely attributed to differences among the analytical frameworks employed for data analysis. The existing frameworks normalizes data against a standard determined from the data to be analyzed. In the present study, a parametric framework based on a strict model for normalization is applied to data acquired using an in-house printed chip and GeneChip. The framework is based on a common statistical characteristic of microarray data, and each data is normalized on the basis of a linear relationship with this model. In the proposed framework, the expressional changes observed and genes selected are coincident between platforms, achieving superior universality of data compared to other methods. http://precedings.nature.com/documents/1746/version/1 oai:nature.com:10101/npre.2008.1746.1 http://hdl.handle.net/10101/npre.2008.1746.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1749.1 2008-04-02T19:57:56Z biotechnology chemistry pharmacology bioinformatics

Systems Pharmacology 2008-04-01T16:12:38Z Ravi Iyengar Biotechnology Chemistry Pharmacology Bioinformatics The slides are from a presentation given by Professor Ravi Iyengar from Mount Sinai School of Medicine at the Drug Forum Meeting #9 that took place in Washington, DC on February 20-21, 2008. The slides describe two projects: one that was published last year, and the other unpublished. These projects used network analysis to explore the relationships between FDA approved drugs and a human protein-protein interaction network. http://precedings.nature.com/documents/1749/version/1 oai:nature.com:10.1038/npre.2008.1749.1 http://dx.doi.org/10.1038/npre.2008.1749.1 Nature Precedings Presentation Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1751.1 2008-04-02T13:10:20Z ecology genetics bioinformatics

Inverse relationship between genetic diversity and epigenetic complexity 2008-04-01T23:42:25Z Shi Huang Ecology Genetics & Genomics Bioinformatics Early studies of molecular evolution revealed a correlation between genetic distance and time of species divergence. This observation provoked the molecular clock hypothesis and in turn the ‘Neutral Theory’, which however remains an incomplete explanation since it predicts a constant mutation rate per generation whereas empirical evidence suggests a constant rate per year. Data inconsistent with the molecular clock hypothesis have steadily accumulated in recent years that show no correlation between genetic distance and time of divergence. It has therefore become a challenge to find a testable idea that can reconcile the seemingly conflicting data sets. Here, an inverse relationship between genetic diversity and epigenetic complexity was deduced from a simple intuition in building complex systems. Genetic diversity, i.e., genetic distance or dissimilarity in DNA or protein sequences between individuals or species, is restricted by the complexity of epigenetic programs. This inverse relationship logically deduces the maximum genetic diversity hypothesis, which suggests that macroevolution from simple to complex organisms involves a punctuational increase in epigenetic complexity that in turn causes a punctuational loss in genetic diversity. The hypothesis explains a diverse set of biological phenomena, including both for and against the correlation between genetic distance and time of divergence.
 http://precedings.nature.com/documents/1751/version/1 oai:nature.com:10101/npre.2008.1751.1 http://hdl.handle.net/10101/npre.2008.1751.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1752.1 2008-04-02T13:19:36Z molecular-cell-biology evolutionary-biology

Idiosyncratic evolution of conserved eukaryote proteins that are similar in sequence to archaeal or bacterial proteins 2008-04-02T03:59:02Z Roy J. Britten Molecular Cell Biology Evolutionary Biology 	Sequence comparisons have been made between the proteins of 571 prokaryote species including 46 archaea and 525 bacteria and the set of human proteins. Highly conserved eukaryotic proteins are often strikingly similar in sequence to archaeal and bacterial proteins. Yet in many cases similarity to archaeal proteins is not correlated to the similarity to bacterial proteins. In these comparisons there are hundreds of eukaryote proteins that match well archeal proteins, but do not match recognizably to bacterial proteins, while thousands of proteins match well to bacterial proteins but not recognizably to archeal proteins. Forty percent of the 21,440 human proteins that significantly match prokaryote proteins are in this extreme idiosyncratic category. These relationships have been preserved over billions of years since the last common ancestor or sharing of protein genes between prokaryotes and eukaryotes. For each of the 21,440 members of this set of human proteins (that make significant matches to any of the 1.8 million proteins in this set of prokaryote species protein libraries) it is certain that each protein has important functions both in prokaryotes and eukaryotes and the precursor proteins have been important in the precursor species of both. That is the only explanation for the preservation of amino acid sequence similarity for the billions of years since the last common ancestor or period of sharing of proteins. Comparisons were made between the proteins of Arabidopsis thaliana and Saccharomyces cerevisiae to the proteins of the 571 prokaryote species. The results agreed with the human comparisons indicating that the conclusions apply to eukaryotes generally. http://precedings.nature.com/documents/1752/version/1 oai:nature.com:10101/npre.2008.1752.1 http://hdl.handle.net/10101/npre.2008.1752.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10.1038/npre.2008.1758.1 2008-04-03T20:16:15Z cancer

Transforming growth factor-beta 1 (tgf-β1) induces angiogenesis through vascular endothelial growth factor (vegf)-mediated apoptosis 2008-04-02T16:38:35Z Giovanni Ferrari B D. Cook Vitaly Terushkin Giuseppe Pintucci Paolo Mignatti Cancer VEGF and TGF-[beta]1 induce angiogenesis but have opposing effects on endothelial cells. VEGF protects endothelial cells from apoptosis; TGF-[beta]1 induces apoptosis. We have previously shown that VEGF / VEGF receptor-2 (flk-1) signaling mediates TGF-[beta]1 induction of apoptosis. This finding raised an important question: Does this mechanism stimulate or inhibit angiogenesis? Here we report that VEGF-mediated apoptosis is required for TGF-[beta]1 induction of angiogenesis. In vitro the apoptotic effect of TGF-[beta]1 on endothelial cells is rapid and followed by a long period in which the cells are refractory to apoptosis induction by TGF-[beta]1. Inhibition of VEGF / flk-1 signaling abrogates formation of vessel-like structures by TGF-[beta]1 with an effect comparable to that of z-VAD, an apoptosis inhibitor. Similarly, genetic deficiency of VEGF abolishes TGF-[beta]1 upregulation of endothelial cell differentiation and formation of vascular structures in embryoid bodies. In vivo TGF-[beta]1 induces endothelial cell apoptosis as rapidly as in vitro. Inhibition of VEGF blocks TGF-[beta]1 induction of both apoptosis and angiogenesis, an effect similar to that of z-VAD. Thus, TGF-[beta]1 induction of angiogenesis requires rapid and transient endothelial cell apoptosis mediated by VEGF/flk-1. This novel, unexpected role of VEGF and flk-1 indicates VEGF-mediated apoptosis as a potential target to control angiogenesis. http://precedings.nature.com/documents/1758/version/1 oai:nature.com:10.1038/npre.2008.1758.1 http://dx.doi.org/10.1038/npre.2008.1758.1 Nature Precedings Manuscript Creative Commons Attribution 3.0 License

oai:nature.com:10101/npre.2008.1760.1 2008-04-03T20:10:36Z ecology bioinformatics

Biodiversity informatics: the challenge of linking data and the role of shared identifiers 2008-04-03T16:43:11Z Roderic Page Ecology Bioinformatics A major challenge facing biodiversity informatics is integrating data stored in widely distributed databases. Initial efforts have relied on taxonomic names as the shared identifier linking records in different databases. However, taxonomic names have limitations as identifiers, being neither stable nor globally unique, and the pace of molecular taxonomic and phylogenetic research means that a lot of information in public sequence databases is not linked to formal taxonomic names. This review explores the use of other identifiers, such as specimen codes and GenBank accession numbers, to link otherwise disconnected facts in different databases. The structure of these links can also be exploited using the PageRank algorithm to rank the results of searches on biodiversity databases. The key to rich integration is a commitment to deploy and reuse globally unique, shared identifiers (such as DOIs and LSIDs), and the implementation of services that link those identifiers. http://precedings.nature.com/documents/1760/version/1 oai:nature.com:10101/npre