http://www.biology-direct.com The latest research articles published by Biology Direct 2010-02-18T00:00:00Z This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ Attempts to engage the scientific community to annotate biological data (such as protein/gene function) stored in databases have not been overly successful. There are several hypotheses on why this has not been successful but it is not clear which of these hypotheses are correct. In this study we have surveyed 50 biologists (who have recently published a paper characterizing a gene or protein) to better understand what would make them interested in providing input/contributions to biological databases. Based on our survey two things become clear: a) database managers need to proactively contact biologists to solicit contributions; and b) potential contributors need to be provided with an easy-to-use interface and clear instructions on what to annotate. Other factors such as 'reward' and 'employer/funding agency recognition' previously perceived as motivators was found to be less important. Based on this study we propose community annotation projects should devote resources to direct solicitation for input and streamlining of the processes or interfaces used to collect this input.ReviewersThis article was reviewed by I. King Jordan, Daniel Haft and Yuriy Gusev http://www.biology-direct.com/content/5/1/12 Raja Mazumder Darren Natale Jessica Anne Ecalnir Julio Lai-Su Yeh Cathy Wu Biology Direct 2010, 5:12 2010-02-18T00:00:00Z doi:10.1186/1745-6150-5-12 Biology Direct 1745-6150 5 12 2010-02-18T00:00:00Z XML Background: The success of invertebrates throughout evolution is an excellent illustration of the efficiency of their defence strategies. Caenorhabditis elegans has proven to be an appropriate model for transcriptome studies of host-pathogen interactions. The aim of this paper is to complement this knowledge by investigating the worm's response to a Staphylococcus aureus infection through a 2-dimensional differential proteomics approach. Results: Different types of growth media in combination with either E. coli OP50 or Staphylococcus aureus were tested for an effect on the worm's lifespan. LB agar was chosen and C. elegans samples were collected 1 h, 4 h, 8 h and 24 h post S. aureus infection or E. coli incubation. Proteomics analyses resulted in the identification of 130 spots corresponding to a total of 108 differentially expressed proteins. Conclusions: Exploring four time-points discloses a dynamic insight of the reaction against a gram-positive infection at the level of the whole organism. The remarkable upregulation after 8 h and 24 h of many enzymes involved in the citric acid cycle might illustrate the cost of fighting off an infection. Intriguing is the downregulation of chaperone molecules, which are presumed to serve a protective role. A comparison with a similar experiment in which C. elegans was infected with the gram-negative Aeromonas hydrophila reveals that merely 9% of the identified spots, some of which even exhibiting an opposite regulation, are present in both studies. Hence, our findings emphasise the complexity and pathogen-specificity of the worm's immune response and form a firm basis for future functional research.ReviewersThis article was reviewed by Itai Yanai, Dieter Wolf and Torben Luebke (nominated by Walter Lutz). http://www.biology-direct.com/content/5/1/11 Annelies Bogaerts Isabel Beets Liesbet Temmerman Liliane Schoofs Peter Verleyen Biology Direct 2010, 5:11 2010-02-17T00:00:00Z doi:10.1186/1745-6150-5-11 Biology Direct 1745-6150 5 11 2010-02-17T00:00:00Z XML Background: The Z-curve is a three dimensional representation of DNA sequences proposed over a decade ago and has been extensively applied to sequence segmentation, horizontal gene transfer detection, and sequence analysis. Based on the Z-curve, a "genome order index," was proposed, which is defined as , where a, c, t, and g are the nucleotide frequencies of A, C, T, and G, respectively. This index was found to be smaller than for almost all tested genomes, which was taken as support for the existence of a constraint on genome composition. A geometric explanation for this constraint has been suggested. Each genome was represented by a point P whose distance from the four faces of a regular tetrahedron was given by the frequencies a, c, t, and g. They claimed that an inscribed sphere of radius contains almost all points corresponding to various genomes, implying that . The distribution of the points P obtained by S was studied using the Z-curve. Results: In this work, we studied the basic properties of the Z-curve using the "genome order index" as a case study. We show that (1) the calculation of the radius of the inscribed sphere of a regular tetrahedron is incorrect, (2) the S index is narrowly distributed, (3) based on the second parity rule, the S index can be derived directly from the Shannon entropy and is, therefore, redundant, and (4) the Z-curve suffers from over dimensionality, and the dimension stands for GC content alone suffices to represent any given genome. Conclusion: The "genome order index" S does not represent a constraint on nucleotide composition. Moreover, S can be easily computed from the Gini-Simpson index and be directly derived from entropy and is redundant. Overall, the Z-curve and S are over-complicated measures to GC content and Shannon H index, respectively.Reviewers:This article was reviewed by Claus Wilke, Joel Bader, Marek Kimmel and Uladzislau Hryshkevich( nominated by Itai Yanai). http://www.biology-direct.com/content/5/1/10 Eran Elhaik Dan Graur Kresimir Josic Biology Direct 2010, 5:10 2010-02-17T00:00:00Z doi:10.1186/1745-6150-5-10 Biology Direct 1745-6150 5 10 2010-02-17T00:00:00Z PDF Background: Grapevine is subjected to numerous pests and diseases resulting in the use of phytochemicals in large quantities. The will to decrease the use of phytochemicals leads to attempts to find alternative strategies, implying knowledge of defence mechanisms. Numerous studies have led to the identification of signalling pathways and regulatory elements involved in defence in various plant species. Nonexpressor of Pathogenesis Related 1 (NPR1) is an important regulatory component of systemic acquired resistance (SAR) in Arabidopsis thaliana. Results: Two putative homologs of NPR1 gene were found in the two sequenced grapevine genomes available in the Genoscope database for line 40024 and in the IASMA database for Pinot noir ENTAV 115. We named these two NPR1 genes of Vitis vinifera : VvNPR1.1 and VvNPR1.2. A PCR-based strategy with primers designed on exons was used to successfully amplify NPR1 gene fragments from different Vitaceae accessions. Sequence analyses show that NPR1.1 and NPR1.2 are highly conserved among the different accessions not only V. vinifera cultivars but also other species. We report nucleotide polymorphisms in NPR1.1 and NPR1.2 from fifteen accessions belonging to the Vitaceae family. The ratio of nonsynonymous to synonymous nucleotide substitutions determines the evolutionary pressures acting on the Vitaceae NPR1 genes. These genes appear to be experiencing purifying selection. In some of the species we have analysed one of the two alleles of NPR1.1 contains a premature stop codon. The deduced amino acid sequences share structural features with known NPR1-like proteins: ankyrin repeats, BTB/POZ domains, nuclear localization signature and cysteines. Phylogenetic analyses of deduced amino acid sequences show that VvNPR1.1 belongs to a first group of NPR1 proteins known as positive regulators of SAR and VvNPR1.2 belongs to a second group of NPR1 proteins whose principal members are AtNPR3 and AtNPR4 defined as negative regulators of SAR. Conclusion: Our study shows that NPR1.1 and NPR1.2 are highly conserved among different accessions in the Vitaceae family. VvNPR1.1 and VvNPR1.2 are phylogenetically closer to the group of positive or negative SAR regulators respectively.ReviewersThis article was reviewed by Fyodor Kondrashov, Purificación López-García and George V. Shpakovski. http://www.biology-direct.com/content/5/1/9 Karine Bergeault Christophe Bertsch Didier Merdinoglu Bernard Walter Biology Direct 2010, 5:9 2010-02-05T00:00:00Z doi:10.1186/1745-6150-5-9 Biology Direct 1745-6150 5 9 2010-02-05T00:00:00Z XML The transcription factor FOXP3 is essential for the development and function of CD4+CD25hiFOXP3+ regulatory T (Treg) cells, but also expressed in activated human helper T cells without acquisition of a regulatory phenotype. This comment focuses on glycoprotein-A repetitions predominant (GARP or LRRC32) recently identified as specific marker of activated human Treg cells, which may provide the missing link toward a better molecular definition of the regulatory phenotype.Reviewers: Dr Jim Di Danto, Dr Benedita Rocha and Dr Werner Solbach. http://www.biology-direct.com/content/5/1/8 Michael Probst-Kepper Jan Buer Biology Direct 2010, 5:8 2010-02-05T00:00:00Z doi:10.1186/1745-6150-5-8 Biology Direct 1745-6150 5 8 2010-02-05T00:00:00Z XML Background: The transition from prokaryotes to eukaryotes was the most radical change in cell organisation since life began, with the largest ever burst of gene duplication and novelty. According to the coevolutionary theory of eukaryote origins, the fundamental innovations were the concerted origins of the endomembrane system and cytoskeleton, subsequently recruited to form the cell nucleus and coevolving mitotic apparatus, with numerous genetic eukaryotic novelties inevitable consequences of this compartmentation and novel DNA segregation mechanism. Physical and mutational mechanisms of origin of the nucleus are seldom considered beyond the long-standing assumption that it involved wrapping pre-existing endomembranes around chromatin. Discussions on the origin of sex typically overlook its association with protozoan entry into dormant walled cysts and the likely simultaneous coevolutionary, not sequential, origin of mitosis and meiosis. Results: I elucidate nuclear and mitotic coevolution, explaining the origins of dicer and small centromeric RNAs for positionally controlling centromeric heterochromatin, and how 27 major features of the cell nucleus evolved in four logical stages, making both mechanisms and selective advantages explicit: two initial stages (origin of 30 nm chromatin fibres, enabling DNA compaction; and firmer attachment of endomembranes to heterochromatin) protected DNA and nascent RNA from shearing by novel molecular motors mediating vesicle transport, division, and cytoplasmic motility. Then octagonal nuclear pore complexes (NPCs) arguably evolved from COPII coated vesicle proteins trapped in clumps by Ran GTPase-mediated cisternal fusion that generated the fenestrated nuclear envelope, preventing lethal complete cisternal fusion, and allowing passive protein and RNA exchange. Finally, plugging NPC lumens by an FG-nucleoporin meshwork and adopting karyopherins for nucleocytoplasmic exchange conferred compartmentation advantages. These successive changes took place in naked growing cells, probably as indirect consequences of the origin of phagotrophy. The first eukaryote had 1-2 cilia and also walled resting cysts; I outline how encystation may have promoted the origin of meiotic sex. I also explain why many alternative ideas are inadequate. Conclusion: Nuclear pore complexes are evolutionary chimaeras of endomembrane- and mitosis-related chromatin-associated proteins. The keys to understanding eukaryogenesis are a proper phylogenetic context and understanding organelle coevolution: how innovations in one cell component caused repercussions on others.ReviewersThis article was reviewed by Anthony Poole, Gáspár Jékely and Eugene Koonin. http://www.biology-direct.com/content/5/1/7 Thomas Cavalier-Smith Biology Direct 2010, 5:7 2010-02-04T00:00:00Z doi:10.1186/1745-6150-5-7 Biology Direct 1745-6150 5 7 2010-02-04T00:00:00Z XML Background: Phosphorylation is the most prevalent post-translational modification on eukaryotic proteins. Multisite phosphorylation enables a specific combination of phosphosites to determine the speed, specificity and duration of biological response. Until recent years, the lack of high quality data limited the possibility for analyzing the properties of phosphorylation at the proteome scale and in the context of a wide range of conditions. Thanks to advances of mass spectrometry technologies, thousands of phosphosites from in-vivo experiments were identified and archived in the public domain. Such resource is appropriate to derive an unbiased view on the phosphosites properties in eukaryotes and on their functional relevance. Results: We present statistically rigorous tests on the spatial and functional properties of a collection of ~70,000 reported phosphosites. We show that the distribution of phosphosites positioning along the protein tends to occur as dense clusters of Serine/Threonines (pS/pT) and between Serine/Threonines and Tyrosines, but generally not as much between Tyrosines (pY) only. This phenomenon is more ubiquitous than anticipated and is pertinent for most eukaryotic proteins: for proteins with ≥ 2 phosphosites, 54% of all pS/pT sites are within 4 amino acids of another site. We found a strong tendency for clustered pS/pT to be activated by the same kinase. Large-scale analyses of phosphopeptides are thus consistent with a cooperative function within the cluster. Conclusions: We present evidence supporting the notion that clusters of pS/pT but generally not pY should be considered as the elementary building blocks in phosphorylation regulation. Indeed, closely positioned sites tend to be activated by the same kinase, a signal that overrides the tendency of a protein to be activated by a single or only few kinases. Within these clusters, coordination and positional dependency is evident. We postulate that cellular regulation takes advantage of such design. Specifically, phosphosite clusters may increase the robustness of the effectiveness of phosphorylation-dependent response.ReviewersReviewed by Joel Bader, Frank Eisenhaber, Emmanuel Levy (nominated by Sarah Teichmann). For the full reviews, please go to the Reviewers' comments section. http://www.biology-direct.com/content/5/1/6 Regev Schweiger Michal Linial Biology Direct 2010, 5:6 2010-01-26T00:00:00Z doi:10.1186/1745-6150-5-6 Biology Direct 1745-6150 5 6 2010-01-26T00:00:00Z XML Background: Divergence of two independently evolving sequences that originated from a common ancestor can be described by two parameters, the asymptotic level of divergence E and the rate r at which this level of divergence is approached. Constant negative selection impedes allele replacements and, therefore, is routinely assumed to decelerate sequence divergence. However, its impact on E and on r has not been formally investigated. Results: Strong selection that favors only one allele can make E arbitrarily small and r arbitrarily large. In contrast, in the case of 4 possible alleles and equal mutation rates, the lowest value of r, attained when two alleles confer equal fitnesses and the other two are strongly deleterious, is only two times lower than its value under selective neutrality. Conclusions: Constant selection can strongly constrain the level of sequence divergence, but cannot reduce substantially the rate at which this level is approached. In particular, under any constant selection the divergence of sequences that accumulated one substitution per neutral site since their origin from the common ancestor must already constitute at least one half of the asymptotic divergence at sites under such selection.ReviewersThis article was reviewed by Drs. Nicolas Galtier, Sergei Maslov, and Nick Grishin. http://www.biology-direct.com/content/5/1/5 Alexey Kondrashov Inna Povolotskaya Dmitry Ivankov Fyodor Kondrashov Biology Direct 2010, 5:5 2010-01-21T00:00:00Z doi:10.1186/1745-6150-5-5 Biology Direct 1745-6150 5 5 2010-01-21T00:00:00Z XML Background: In several studies, secondary structures of ribosomal genes have been used to improve the quality of phylogenetic reconstructions. An extensive evaluation of the benefits of secondary structure, however, is lacking. Results: This is the first study to counter this deficiency. We inspected the accuracy and robustness of phylogenetics with individual secondary structures by simulation experiments for artificial tree topologies with up to 18 taxa and for divergency levels in the range of typical phylogenetic studies. We chose the internal transcribed spacer 2 of the ribosomal cistron as an exemplary marker region. Simulation integrated the coevolution process of sequences with secondary structures. Additionally, the phylogenetic power of marker size duplication was investigated and compared with sequence and sequence-structure reconstruction methods. The results clearly show that accuracy and robustness of Neighbor Joining trees are largely improved by structural information in contrast to sequence only data, whereas a doubled marker size only accounts for robustness. Conclusions: Individual secondary structures of ribosomal RNA sequences provide a valuable gain of information content that is useful for phylogenetics. Thus, the usage of ITS2 sequence together with secondary structure for taxonomic inferences is recommended. Other reconstruction methods as maximum likelihood, bayesian inference or maximum parsimony may equally profit from secondary structure inclusion.ReviewersThis article was reviewed by Shamil Sunyaev, Andrea Tanzer (nominated by Frank Eisenhaber) and Eugene V. Koonin.Open peer reviewReviewed by Shamil Sunyaev, Andrea Tanzer (nominated by Frank Eisenhaber) and Eugene V. Koonin. For the full reviews, please go to the Reviewers' comments section. http://www.biology-direct.com/content/5/1/4 Alexander Keller Frank Forster Tobias Muller Thomas Dandekar Joerg Schultz Matthias Wolf Biology Direct 2010, 5:4 2010-01-15T00:00:00Z doi:10.1186/1745-6150-5-4 Biology Direct 1745-6150 5 4 2010-01-15T00:00:00Z XML Background: The bacterial elongation factor P (EF-P) is strictly conserved in bacteria and essential for protein synthesis. It is homologous to the eukaryotic translation initiation factor 5A (eIF5A). A highly conserved eIF5A lysine is modified into an unusual amino acid derived from spermidine, hypusine. Hypusine is absolutely required for eIF5A's role in translation in Saccharomyces cerevisiae. The homologous lysine of EF-P is also modified to a spermidine derivative in Escherichia coli. However, the biosynthesis pathway of this modification in the bacterial EF-P is yet to be elucidated.Presentation of the HypothesisHere we propose a potential mechanism for the post-translational modification of EF-P. By using comparative genomic methods based on physical clustering and phylogenetic pattern analysis, we identified two protein families of unknown function, encoded by yjeA and yjeK genes in E. coli, as candidates for this missing pathway. Based on the analysis of the structural and biochemical properties of both protein families, we propose two potential mechanisms for the modification of EF-P.Testing the hypothesisThis hypothesis could be tested genetically by constructing a bacterial strain with a tagged efp gene. The tag would allow the purification of EF-P by affinity chromatography and the analysis of the purified protein by mass spectrometry. yjeA or yjeK could then be deleted in the efp tagged strain and the EF-P protein purified from each mutant analyzed by mass spectrometry for the presence or the absence of the modification. This hypothesis can also be tested by purifying the different components (YjeK, YjeA and EF-P) and reconstituting the pathway in vitro.Implication of the hypothesisThe requirement for a fully modified EF-P for protein synthesis in certain bacteria implies the presence of specific post-translational modification mechanism in these organisms. All of the 725 bacterial genomes analyzed, possess an efp gene but only 200 (28%) possess both yjeA and yjeK genes. In the other organisms, EF-P may be modified by another pathway or the translation machinery must have adapted to the lack of EF-P modification. Our hypotheses, if confirmed, will lead to the discovery of a new post-translational modification pathway.ReviewersThis article was reviewed by Céline Brochier-Armanet, Igor B. Zhulin and Mikhail Gelfand. For the full reviews, please go to the Reviewers' reports section. http://www.biology-direct.com/content/5/1/3 Marc Bailly Valerie de Crecy-Lagard Biology Direct 2010, 5:3 2010-01-13T00:00:00Z doi:10.1186/1745-6150-5-3 Biology Direct 1745-6150 5 3 2010-01-13T00:00:00Z XML