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Krupovic M.,Institute Pasteur Paris | Prangishvili D.,Institute Pasteur Paris | Hendrix R.W.,University of Pittsburgh | Bamford D.H.,Institute of Biotechnology
Microbiology and Molecular Biology Reviews | Year: 2011

Prokaryotes, bacteria and archaea, are the most abundant cellular organisms among those sharing the planet Earth with human beings (among others). However, numerous ecological studies have revealed that it is actually prokaryotic viruses that predominate on our planet and outnumber their hosts by at least an order of magnitude. An understanding of how this viral domain is organized and what are the mechanisms governing its evolution is therefore of great interest and importance. The vast majority of characterized prokaryotic viruses belong to the order Caudovirales, double-stranded DNA (dsDNA) bacteriophages with tails. Consequently, these viruses have been studied (and reviewed) extensively from both genomic and functional perspectives. However, albeit numerous, tailed phages represent only a minor fraction of the prokaryotic virus diversity. Therefore, the knowledge which has been generated for this viral system does not offer a comprehensive view of the prokaryotic virosphere. In this review, we discuss all families of bacterial and archaeal viruses that contain more than one characterized member and for which evolutionary conclusions can be attempted by use of comparative genomic analysis. We focus on the molecular mechanisms of their genome evolution as well as on the relationships between different viral groups and plasmids. It becomes clear that evolutionary mechanisms shaping the genomes of prokaryotic viruses vary between different families and depend on the type of the nucleic acid, characteristics of the virion structure, as well as the mode of the life cycle. We also point out that horizontal gene transfer is not equally prevalent in different virus families and is not uniformly unrestricted for diverse viral functions. Copyright © 2011, American Society for Microbiology. All Rights Reserved. Source

Van de N.,Hanoi Medical University | Hoa Le T.,Institute of Biotechnology
Experimental Parasitology | Year: 2011

The prevalence of fish-borne trematodes in humans and their molecular identification was investigated in the Rang Dong commune of Nam Dinh province, Vietnam, between January 2009 and December 2010. A total of 405 people in this commune were interviewed on the habit of eating raw fish and all of their stool samples were collected using the Kato-Katz technique for examination of the presence of fish-borne trematodes. The worms (and eggs) were first morphologically examined, counted, described and identified, then the representative isolates were subjected for molecular species confirmation. A total of 385 adult flukes collected from 10 patients were morphologically identified to species and defined as Clonorchis sinensis (14.58%) in Opisthorchiidae family, Haplorchis taichui (32.29%), Haplorchis pumilio (52.08%) and Centrocestus formosanus (1.04%) in Heterophyidae family. A high rate (77.8%) of the interviewees was found to have the habit of eating raw fish. This habit was attributed to the high infection rate of fish-borne trematode in humans (22.72%; OR = 2.486). The infection rate of fish-borne trematodes in males was higher (29.3%) than that in females (16.0%) and increased by age, reaching the highest in the patients aged 40-59 years (28.2-28.7%). The infection intensity of fish-borne trematode was found light (336 EPG). Adult flukes were collected from a group of the patients with the highest intensity of infection and subjected to molecular and phylogenetic analysis using a portion (326. bp) of mitochondrial cox1. Phylogenetic tree inferred from cox1 sequences using sequence data for 34 isolates of opisthorchid, heterophyid, fasciolid, paragonimid, schistosomid trematodes and taeniid cestodes revealed that they are distinct groups. The newly collected with the known clonorchid and heterophyid isolates form the well defined taxonomic groups, respectively, confirming that C. sinensis and Haplorchis spp. (H. pumilio and H. taichui) were among the collected samples. © 2011 Elsevier Inc. Source

Human diseases involving protein misfolding and aggregation have received increasing attention in recent years. Alzheimer's disease and other diseases associated with aging are sweeping the developed countries whose populations are rapidly aging. Recent progress has improved our knowledge about molecular and cellular pathogenesis of these diseases. For more than 20 years, multiple diseases such as Alzheimer's and Parkinson's diseases have been associated with accumulation of abnormal protein fibrils. These self-assembling fibrils, referred as "amyloid," have been considered the pathogenic molecules that cause cellular degeneration. Accumulation of fibrillar Aβ in plaques underlies the theory for Alzheimer's disease. Recent experiments have provided evidence that fibrils are not the only neurotoxins. Soluble oligomers and protofibrils play a crucial role in causing cellular dysfunction and death. These oligomers, the missing links in the original amyloid cascade hypothesis, have been incorporated into an updated amyloid cascade. Despite new information gained, there is no disease-modifying treatment. New insights into disease mechanisms and new therapeutic strategies give hope for change. Source

Nguyen H.C.,Institute of Biotechnology | Hoefgen R.,Max Planck Institute of Molecular Plant Physiology | Hesse H.,Max Planck Institute of Molecular Plant Physiology
Journal of Experimental Botany | Year: 2012

With the aim of increasing the cysteine level in rice (Oryza sativa L.) and thus improving its nutritional quality, transgenic rice plants were generated expressing an Escherichia coli serine acetyltransferase isoform (EcSAT), the enzyme synthesizing O-acetylserine, the precursor of cysteine. The gene was fused to the transit peptide of the Arabidopsis Rubisco and driven by a ubiquitin promoter to target the enzyme to plastids. Twenty-two transgenic plants were examined for transgene protein expression, and five lines with a high expression level and enzymatic activity, respectively, were selected for further analysis. In these lines, the contents of cysteine and glutathione increased 2.4-fold and 2-fold, respectively. More important is the increase in free methionine and methionine incorporated into the water-soluble protein fraction in seeds. Free methionine increased in leaves up to 2.7-fold, in seeds up to 1.4-fold, and bound to seed proteins up to 4.8-fold, respectively, while the bound methionine level remained constant or even decreased in leaves. Notably, the transgenic lines exhibited higher isoleucine, leucine, and valine contents (each up to 2-fold depending on tissue, free, or bound), indicating a potential conversion of methionine via methionine γ-lyase to isoleucine. As the transgenic rice plants overexpressing EcSAT had significantly higher levels of both soluble and protein-bound methionine, isoleucine, cysteine, and glutathione in rice they may represent a model and target system for improving the nutritional quality of cereal crops. © 2012 The Authors. Source

Margelevicius M.,Institute of Biotechnology | Venclovas C.,Institute of Biotechnology
BMC Bioinformatics | Year: 2010

Background: Detection of common evolutionary origin (homology) is a primary means of inferring protein structure and function. At present, comparison of protein families represented as sequence profiles is arguably the most effective homology detection strategy. However, finding the best way to represent evolutionary information of a protein sequence family in the profile, to compare profiles and to estimate the biological significance of such comparisons, remains an active area of research.Results: Here, we present a new homology detection method based on sequence profile-profile comparison. The method has a number of new features including position-dependent gap penalties and a global score system. Position-dependent gap penalties provide a more biologically relevant way to represent and align protein families as sequence profiles. The global score system enables an analytical solution of the statistical parameters needed to estimate the statistical significance of profile-profile similarities. The new method, together with other state-of-the-art profile-based methods (HHsearch, COMPASS and PSI-BLAST), is benchmarked in all-against-all comparison of a challenging set of SCOP domains that share at most 20% sequence identity. For benchmarking, we use a reference ("gold standard") free model-based evaluation framework. Evaluation results show that at the level of protein domains our method compares favorably to all other tested methods. We also provide examples of the new method outperforming structure-based similarity detection and alignment. The implementation of the new method both as a standalone software package and as a web server is available at http://www.ibt.lt/bioinformatics/coma.Conclusion: Due to a number of developments, the new profile-profile comparison method shows an improved ability to match distantly related protein domains. Therefore, the method should be useful for annotation and homology modeling of uncharacterized proteins. © 2010 Margelevičius and Venclovas; licensee BioMed Central Ltd. Source

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