http://precedings.nature.com/subjects/microbiology/ Recently posted documents in Microbiology Nature Publishing Group en Nature Precedings http://precedings.nature.com/images/header_logo.gif http://precedings.nature.com http://precedings.nature.com/documents/3974/version/1 CD4 count is an important immunological marker of disease progression in HIV seropositive patients. This study was carried out to determine the effect of malaria or fever of unknown origin on the population of CD4+ T lymphocytes of HIV seropositive patients attending the highly active antiretroviral therapy (HAART) clinic of the University of Ilorin Teaching Hospital, Ilorin, Nigeria. 36 subjects were selected for this study. Ongoing history of fever was used as a case definition for malaria and malaria was confirmed from microscopic examination of thick and thin film of blood sample obtained from the patients during presentation with fever. The CD4 count was evaluated during presentation of fever and post-fever using flow cytometry. There was significant decrease in CD4 count of the patients. However, upon classifying the patients into 2 groups – those that returned to the clinic after a week and those that returned after a month – a significant increase in CD4 count was noticed in the group that returned after a week, while a significant decrease was noticed in the group that returned after a month (at p value of 95%). Further classification of the patients based on presence of malaria parasite, and body temperature resulted in varying effects on CD4 count post-fever (in the general group, 27 were positive for malaria parasites. Of these 27, there was an increase in CD4 count in 9 (33.3%). However in the group that returned after a week, all 6 (100%) that were positive for malaria parasites showed increase in CD4 count. Five (26.3%) of the 19 patients that had body temperature within the range of 35.5-37.4oC showed an increase in CD4 count, while 7 (41.2%) the 17 patients that had body temperature of 37.5oC and above showed an increase in CD4 count. The results led to the conclusion that while some components of the immune response to malaria could strengthen the immune system of HIV seropositive patients by increasing their CD4 count, other components will suppress their immunity by decreasing their CD4 count, accelerating the progression to AIDS. http://precedings.nature.com/documents/3974/version/1 Fri, 13 Nov 2009 13:52:13 UTC Evaluation of CD4+ T Cells in HIV Patients Presenting with Malaria at the University of Ilorin Teaching Hospital Nigeria hdl:10101/npre.2009.3974.1 2009-11-13 Olatunji M. Kolawole Nature Precedings 2009-11-13T13:52:13Z Manuscript Microbiology http://creativecommons.org/licenses/by/3.0/ http://dx.doi.org/10.1038/npre.2009.3954.1 In an era of nutraceuticular research, ‘Noni’ fruit is considered as a panacea because of the profound claim on its medicinal uses in treating many diseases inclusive of infections of microbial origin. Hence, the present study was done to know the antibacterial activity of aqueous extracts from ripe and unripe fruits of ‘Noni’ Morinda citrifolia L on gastroenteritic and pyogenic bacteria. The study was done for eight gastroenteritic bacteria and six pyogenic bacteria. The estimation of antibacterial activity of the ripe fruit & unripe fruit extract were carried out by serial two fold tube dilution techniques. Minimum Bactericidal Concentration of the ripe as well as unripe fruit extracts for the susceptible bacteria were estimated by Recovery plate method. Both the Unripe and ripe fruit extracts exhibited nearly equal and effective activity. As the unripe fruit is devoid of unpleasant odour, the unripe fruit is preferable over the ripe fruit extract http://dx.doi.org/10.1038/npre.2009.3954.1 Mon, 09 Nov 2009 14:38:04 UTC In Vitro Bactericidal Activities of Extracts From Ripe and Unripe Fruit of ‘Noni’ doi:10.1038/npre.2009.3954.1 2009-11-09 Rajarajan Swaminathan Nature Precedings 2009-11-09T14:38:04Z Manuscript Microbiology Molecular Cell Biology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3898/version/1 A bacterial strain, designated Aeromonas sp. kumar, was isolated from a water sample collected from Red tide Bloom occurred in the region of Gulf of Mannar region, Puthumadam Coast, India and the strain was identified using 16S rRNA based identification. During the sample collection, microbiology analysis was done to study the morphology of the bacteria. Pure culture of strain was maintained through out the study. DNA was isolated and sequenced using 16S rRNA primers. A length of 1452 nucleotide was sequenced and was put in public data base for obtaining accession number. The sequence was studied using MEGA 4, to estimate the evolutionary distances and to construct the Phylogenetic tree. Along with that Regulatory elements and Transcription factors were studied using BPROM tool. In genetics, a promoter is a region of DNA that facilitates the transcription of a particular gene. Promoters are typically located near the genes they regulate, on the same strand and upstream (towards the 5’ region of the sense strand). The objective of the study is to predict the regulatory elements which are -10 box, -35box and three Transcription Factors (rpoD19, rpoD17 and araC) with their binding sites in the 16S rRNA gene of Aeromonas sp. kumar. The gene bank accession number for 16S rRNA gene of Aeromonas sp. kumar is FJ896014. http://precedings.nature.com/documents/3898/version/1 Wed, 28 Oct 2009 14:41:34 UTC 16S rRNA based identification of Aeromonas sp. kumar by constructing phylogenetic tree and identification of regulatory elements from the harmful Red Tide bloom, Gulf of Mannar hdl:10101/npre.2009.3898.1 2009-10-28 P. Kumar Nature Precedings 2009-10-28T14:41:34Z Manuscript Ecology Microbiology Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3886/version/1 Viruses are the most abundant life forms and the repertoire of viral genes is greater than that of cellular genes. It is also evident that viruses have played a major role in driving cellular evolution, and yet, viruses are not part of mainstream biology, nor are they included in the Tree of Life. A reason for this major paradox in biology is the misleading dogma of viruses as viral particles and their enigmatic evolutionary origin. This article presents an alternative view about the nature of viruses based on their properties during the intracellular stage of their life cycle, when viruses express features comparable to those of many parasitic cellular species. Supporting this view about the nature of viruses is a novel hypothetical evolutionary model for their origin from parasitic cellular species that fused with their host cells. By losing their membrane and cellular structure within the host cell, these new types of parasitic species gained full access to precursors for the synthesis of their specific molecules and to the host’s information processing machineries, such as translation, which created unique parasitic and evolutionary opportunities. To identify viruses during their intracellular stage of their life cycle, in which their specific molecules are free or dispersed within the host cell, this paper introduces the concept of “molecular structure” and labels viruses as “molecular organisms.” Among the extant viruses, the life cycle of poxviruses and other complex viruses that fuse with their host cells provides compelling evidence for the fusion model. One of the most remarkable implications of fusion model is that new viral lineages originated from parasitic cellular species throughout the history of life, and that this process might still be active. Surprisingly, it appears that several parasitic cellular species are currently evolving into molecular organisms. More remarkably though, according to this model, several parasites that are currently classified as cellular organisms are in fact genuine molecular organisms. The current evidence for the fusion hypothesis is strong and it is fully testable using both experimental and phylogenetic approaches. The academic and research implications of this model, which supports the inclusion of viruses in the Tree of Life, are highly significant. Some of these implications are discussed in more detail in two other articles of this series, which presents a unifying model for the origin and evolution of cellular and viral domains, including the origin of life. http://precedings.nature.com/documents/3886/version/1 Fri, 23 Oct 2009 11:33:49 UTC The Origin and Evolution of Viruses as Molecular Organisms hdl:10101/npre.2009.3886.1 2009-10-23 Claudiu I. Bandea Nature Precedings 2009-10-23T11:33:49Z Manuscript Genetics & Genomics Microbiology Evolutionary Biology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3887/version/1 Transmissible spongiform encephalopathies (TSEs), or prion diseases, are a group of incurable neurodegenerative disorders, including Kuru and Creutzfeldt-Jakob disease in humans, “mad cow” disease in cattle, and scrapie in sheep. This paper presents structural, genetic, and evolutionary evidence supporting an endogenous TSE virus model that integrates the three major traditional views on the nature of TSE pathogens, the conventional virus view, the prion hypothesis, and the virino concept, into a novel conceptual and evolutionary framework. According to this model, the TSE pathogens are symbiotic endogenous viruses that inadvertently produce transmissible viral particles that lack the viral genome and are composed primarily of the viral prion protein (PrP). Production of defective viral particles that contain a partial genome or lack the viral genome entirely is a relatively common event in the life cycle of many viruses. Similar to the normal viral particles, which contain a genome, these defective viral particles can be transmitted to new host cells. Obviously, in the absence of viral genome, these protein-only viral particles cannot establish a productive infection. However, if these viral particles enter a host cell that carries the parental or a related virus and induce the production of similar protein-only particles, then they would appear as self-replicating, protein-only infectious pathogens if mistakenly taken out from the context of the viral life cycle. This misconception, which is rooted into the current dogma of viruses as viral particles, led to the development of the prion theory. The endogenous TSE virus model is consistent with the TSE data and offers solutions to many enigmatic features associated with TSE, including the function of PrP that, despite more than two decades of TSE research conducted primarily within the framework of the prion hypothesis, is still not known. According to the TSE endogenous virus model, PrP is the protein of an endogenous virus that has co-evolved with their vertebrate hosts by providing a protective function against pathogenic viruses. The evidence for the endogenous TSE virus model and for the antiviral protective function of PrP is strong, and they are fully open to additional experimental testing. The endogenous virus model opens the TSE research field to new interpretations and directions, both in basic research and in associated biomedical and public health fields, and could lead to development of new diagnostic and therapeutic approaches. http://precedings.nature.com/documents/3887/version/1 Fri, 23 Oct 2009 11:27:57 UTC Endogenous Viral Etiology of Prion Diseases hdl:10101/npre.2009.3887.1 2009-10-23 Claudiu I. Bandea Nature Precedings 2009-10-23T11:27:57Z Manuscript Microbiology Neuroscience Evolutionary Biology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3888/version/1 The cellular theory on the nature of life has been one of the first major advancements in biology. Viruses, however, are the most abundant life forms, and their exclusion from mainstream biology and the Tree of Life (TOL) is a major paradox in biology. This article presents a broad, unifying scenario on the origin and evolution of cellular and viral domains that challenges the conventional views about the history of life and supports a TOL that includes viruses. Co-evolution of viruses and their host cells has led to some of the most remarkable developments and transitions in the evolution of life, including the origin of non-coding DNA as a genomic protective device against viral insertion damage. However, one of the major fundamental evolutionary developments driven by viruses was probably the origin of cellular domains – Bacteria, Archaea and Eukarya – from the Last Universal Common Ancestor (LUCA) lineage, by evolving anti-fusion mechanisms. Consistent with a novel fusion/fission model for the population mode of evolution of LUCA, this paper presents a “cell-like world” model for the origin of life. According to this model the evolution of coupled replication, transcription and translation system (RT&T) occurred within non-living cell-like compartments (CCs). In this model, the ancestral ribosome originated as template-based RNA synthesizing machinery. The origin of the cellular genome as a centralized unit for storage and replication of genetic information within the CCs facilitated the evolution of the ancestral ribosome into a powerful translation machinery – the modern ribosome. After several hundred millions of years of providing an enclosed environment and fusion/fission based exchanges necessary for the population mode of evolution of the basic metabolism and the RT&T, the CCs evolved into the first living entities on earth – the LUCA lineage. The paper concludes with a proposal for a TOL that integrates the co-evolution of cellular and viral domains. This is one of a series of three articles that present a unifying scenario on the origin and evolution of viral and cellular domains, including the origin of life, which has significant t bio-medical implications and could lead to a significant paradigm shift in biology. http://precedings.nature.com/documents/3888/version/1 Fri, 23 Oct 2009 11:11:22 UTC A Unifying Scenario on the Origin and Evolution of Cellular and Viral Domains hdl:10101/npre.2009.3888.1 2009-10-23 Claudiu I. Bandea Nature Precedings 2009-10-23T11:11:22Z Manuscript Genetics & Genomics Immunology Microbiology Evolutionary Biology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3883/version/1 Background. Our studies on the role of cholesterol in prion infection/replication showed that brains and peripheral cells of sheep susceptible to or suffering from Scrapie were characterized by an altered cholesterol homeostasis compared to animals with a scrapie-resistant genotype, and that drugs influencing cholesterol esterification were endowed with selective anti-prion activity in N2a cell lines infected with the 22L and RML prion strains. Results. In prion-infected N2a cell lines we now report increased anti-prion activity of dual-drug combinations consisting of cholesterol ester modulators associated with prion inhibitors Synergism was obtained with the cholesterol ester modulators everolimus, pioglitazone, progesterone, and verapamil associated with the anti-prion chlorpromazine, and with everolimus and pioglitazone associated with the anti-prion quinacrine. Comparative lipid analyses in prion-infected and non-infected N2a cells by colorimetric, enzymatic, and chemical means, clearly demonstrated a derangement of type and distribution of cholesterol esters, free cholesterol, and triglycerides in the infected N2a cells. Although single-drug treatments influenced lipid syntheses, only the combined-drug treatments appeared to restore a lipid profile similar to that of untreated-uninfected cells. Conclusions. We conclude that the anti-prion synergistic effect of cholesterol ester modulators with the cholesterol metabolism interfering anti-prion drugs chlorpromazine and quinacrine may arise from the ability of combined drugs to re-establish the intracellular lipid profile of untreated-uninfected cells. Overall, these data suggest that inhibition of prion replication can be readily potentiated by combinatorial drug treatments, and that steps of cholesterol/cholesterol ester metabolism may represent suitable targets. http://precedings.nature.com/documents/3883/version/1 Wed, 21 Oct 2009 15:17:23 UTC In vitro synergistic anti-prion effect of cholesterol ester modulators hdl:10101/npre.2009.3883.1 2009-10-21 Fabrizio Angius Nature Precedings 2009-10-21T15:17:23Z Manuscript Microbiology Neuroscience Pharmacology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3845/version/1 Many important cellular processes are regulated by reaction-diffusion (RD) of molecules that takes place both in the cytoplasm and on the membrane. To model and analyze such multicompartmental processes, we developed a lattice-based Monte Carlo method, Spatiocyte that supports RD in volume and surface compartments at single molecule resolution. Stochasticity in RD and the excluded volume effect brought by intracellular molecular crowding, both of which can significantly affect RD and thus, cellular processes, are also supported. We verified the method by comparing simulation results of diffusion, irreversible and reversible reactions with the predicted analytical and best available numerical solutions. Moreover, to directly compare the localization patterns of molecules in fluorescence microscopy images with simulation, we devised a visualization method that mimics the microphotography process by showing the trajectory of simulated molecules averaged according to the camera exposure time. In the rod-shaped bacterium Escherichia coli, the division site is suppressed at the cell poles by periodic pole-to-pole oscillations of the Min proteins (MinC, MinD and MinE) arising from carefully orchestrated RD in both cytoplasm and membrane compartments. Using Spatiocyte we could model and reproduce the in vivo MinDE localization dynamics by accounting for the established properties of MinE. Our results suggest that the MinE ring, which is essential in preventing polar septation, is largely composed of MinE that is transiently attached to the membrane independently after recruited by MinD. Overall, Spatiocyte allows simulation and visualization of complex spatial and reaction-diffusion mediated cellular processes in volumes and surfaces. As we showed, it can potentially provide mechanistic insights otherwise difficult to obtain experimentally. http://precedings.nature.com/documents/3845/version/1 Fri, 09 Oct 2009 09:45:29 UTC A new multicompartmental reaction-diffusion modeling method links transient membrane attachment of E. coli MinE to E-ring formation hdl:10101/npre.2009.3845.1 2009-10-09 Satya N. V. Arjunan Nature Precedings 2009-10-09T09:45:29Z Manuscript Developmental Biology Microbiology Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://dx.doi.org/10.1038/npre.2009.3805.1 Alpine ibex is characterized by strong sexual differences, both morphological and in population dynamics. Host sex has been shown to strongly affect parasite load with males usually more infected than females. Moreover ibex exhibit a peculiar pattern of survival with subadult males having a slow growing rate coupled with high survival which rapidly decline in old individual. This peculiar life history has been suggested to have been developed as adaptation to an harsh environment. In this way by investing fewer resources in growing the ibex can direct more energy in survival. At the same time the investment in immunodefence can change over the age. To verify the hypothesis that sex and age affect parasite infection, we analysed the abomasal parasite community of swiss ibexes shot during the 2007 hunting season. We analysed the parasite community of 31 abomasa coming from 17 males,12 females, ranging from 1 to 16 years old. The ibex analysed harboured a mean of 1472 helminth/individual. Seven parasites species have been identified with Teladorsagia circumcincta and Marshallagia marshalli covering the 90% of total parasite count. The mean abundance of total parasite count and of M. marshalli was different between sexes, with more parasites found in males. Age alone did not show any significant effect, but its interaction with sex evidenced different relationship such as T. circumcincta increased with age in males and decreased in females.While these data suggest the influence of sex and age on parasitic infection a comparison with other sampling areas, year and season is needed. http://dx.doi.org/10.1038/npre.2009.3805.1 Fri, 25 Sep 2009 19:02:50 UTC Host factors affecting abomasal parasites in Alpine Ibex doi:10.1038/npre.2009.3805.1 2009-09-28 Nicola Ferrari Nature Precedings 2009-09-25T19:02:50Z Poster Ecology Microbiology Earth & Environment http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3776/version/1 The emergence of tuberculosis resistant to multiple, first- and second-line antibiotics poses challenges to a global control strategy that relies on standard drug treatment regimens. The high drug-resistant strains of Mycobacterium tuberculosis (Mtb) have been implicated in outbreaks and have been found throughout the world; a comprehensive understanding, the magnitude of this threat requires an accurate assessment of the worldwide burden of resistance. In an attempt to design anti-TB drugs, the target chosen is a key enzyme of Mtb, O-Succinylbenzoate synthase (OSBS), which is an attractive target for its role in electron transport chain as OSBS is not available in humans. An attempt has been to built the 3-D structure of Mtb-OSBS using online Swiss model server. With sequence alignment and scan motif identification, the importance of evolutionarily significant residues that are of functional importance for ligand binding and that form active sites were well established. Molecular simulation calculations of Mtb-OSBS model indicated evolutionarily conserve residues (Lys110 and Lys212) are the best in molecular interaction with substrate 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC). The in silico mutational analysis of Mtb-OSBS model showed the evolutionarily conserved residues that are essential for catalytic activity. It has been found that active site amino acids of Mtb-OSBS are very important to maintain activity of the enzyme, which provides a novel approach to design new pharmacophore SHCHC substrate analogs against Mtb-OSBS. A series of SHCHC substrate analogs (1–100) compounds have been docked with the amino acid residues at the active site of the Mtb-OSBS enzyme, using AutoDock 4.0, a program employed to perform automated molecular docking. The free energies of binding (∆G) and inhibition constants (Ki) of the docked compounds were calculated by the Lamarckian Genetic Algorithm (LGA). Excellent to good correlations between the calculated and experimental Ki values were reported. http://precedings.nature.com/documents/3776/version/1 Fri, 18 Sep 2009 16:35:16 UTC Prediction of Evolutionarily important catalytic amino acid of Mycobacterium tuberculosis O-Succinylbenzoate synthase through in silico mutational analysis hdl:10101/npre.2009.3776.1 2009-09-18 Suresh Kumar Chitta Nature Precedings 2009-09-18T16:35:16Z Poster Biotechnology Microbiology Pharmacology Bioinformatics http://creativecommons.org/licenses/by/3.0/