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/ http://jbiol.com/mostviewed/ Most viewed articles in last 30 days from Journal of Biology (ISSN 1475-4924) published by BioMed Central Transcription and metabolite analysis is a powerful way to reveal physiological shifts in response to environmental pollution. Recent studies on earthworms, including one in BMC Biology, show that the type of pollution and its availability for uptake by organisms can differentially affect transcription and metabolism. http://jbiol.com/content/7/6/19 Nico M van Straalen and Dick Roelofs Journal of Biology 2008, 7:19 Number of accesses: 1199 2008-07-14 doi:10.1186/jbiol80 Journal of Biology 1475-4924 7 19 2008-07-14 A recent study in BMC Pharmacology presents a network of drugs and the therapies in which they are used. Network approaches open new ways of predicting novel drug targets and overcoming the cellular robustness that can prevent drugs from working. http://jbiol.com/content/7/6/20 Zoltan Spiro, Istvan A Kovacs and Peter Csermely Journal of Biology 2008, 7:20 Number of accesses: 1137 2008-07-31 doi:10.1186/jbiol81 Journal of Biology 1475-4924 7 20 2008-07-31 Insulin-like growth factor (IGF) binding proteins provide a layer of complexity to the insulin/IGF signaling system in mammals, but only now, in a recent study in Journal of Biology, has one such protein been functionally characterized in Drosophila. http://jbiol.com/content/7/6/18 Nazif Alic and Linda Partridge Journal of Biology 2008, 7:18 Number of accesses: 940 2008-07-07 doi:10.1186/jbiol79 Journal of Biology 1475-4924 7 18 2008-07-07 Background: Cancer treatment with a variety of chemotherapeutic agents often is associated with delayed adverse neurological consequences. Despite their clinical importance, almost nothing is known about the basis for such effects. It is not even known whether the occurrence of delayed adverse effects requires exposure to multiple chemotherapeutic agents, the presence of both chemotherapeutic agents and the body's own response to cancer, prolonged damage to the blood-brain barrier, inflammation or other such changes. Nor are there any animal models that could enable the study of this important problem. Results: We found that clinically relevant concentrations of 5-fluorouracil (5-FU; a widely used chemotherapeutic agent) were toxic for both central nervous system (CNS) progenitor cells and non-dividing oligodendrocytes in vitro and in vivo. Short-term systemic administration of 5-FU caused both acute CNS damage and a syndrome of progressively worsening delayed damage to myelinated tracts of the CNS associated with altered transcriptional regulation in oligodendrocytes and extensive myelin pathology. Functional analysis also provided the first demonstration of delayed effects of chemotherapy on the latency of impulse conduction in the auditory system, offering the possibility of non-invasive analysis of myelin damage associated with cancer treatment. Conclusions: Our studies demonstrate that systemic treatment with a single chemotherapeutic agent, 5-FU, is sufficient to cause a syndrome of delayed CNS damage and provide the first animal model of delayed damage to white-matter tracts of individuals treated with systemic chemotherapy. Unlike that caused by local irradiation, the degeneration caused by 5-FU treatment did not correlate with either chronic inflammation or extensive vascular damage and appears to represent a new class of delayed degenerative damage in the CNS. http://jbiol.com/content/7/4/12 Ruolan Han, Yin M Yang, Joerg Dietrich, Anne Luebke, Margot Mayer-Pröschel and Mark Noble Journal of Biology 2008, 7:12 Number of accesses: 791 2008-04-22 doi:10.1186/jbiol69 Journal of Biology 1475-4924 7 12 2008-04-22 The transfer-messenger ribonucleoprotein (tmRNP), which is composed of RNA and a small protein, small protein B (SmpB), recycles ribosomes that are stalled on broken mRNAs lacking stop codons and tags the partially translated proteins for degradation. Although it is not yet understood how the ribosome gets from the 3' end of the truncated message onto the messenger portion of the tmRNA to add the tag, a recent study in BMC Biology has shed some light on this astonishing feat. http://jbiol.com/content/7/5/17 Jacek Wower, Iwona K Wower and Christian Zwieb Journal of Biology 2008, 7:17 Number of accesses: 481 2008-06-30 doi:10.1186/jbiol78 Journal of Biology 1475-4924 7 17 2008-06-30 Background: Insulin and insulin-like growth factors (IGFs) signal through a highly conserved pathway and control growth and metabolism in both vertebrates and invertebrates. In mammals, insulin-like growth factor binding proteins (IGFBPs) bind IGFs with high affinity and modulate their mitogenic, anti-apoptotic and metabolic actions, but no functional homologs have been identified in invertebrates so far. Results: Here, we show that the secreted Imaginal morphogenesis protein-Late 2 (Imp-L2) binds Drosophila insulin-like peptide 2 (Dilp2) and inhibits growth non-autonomously. Whereas over-expressing Imp-L2 strongly reduces size, loss of Imp-L2 function results in an increased body size. Imp-L2 is both necessary and sufficient to compensate Dilp2-induced hyperinsulinemia in vivo. Under starvation conditions, Imp-L2 is essential for proper dampening of insulin signaling and larval survival. Conclusion: Imp-L2, the first functionally characterized insulin-binding protein in invertebrates, serves as a nutritionally controlled suppressor of insulin-mediated growth in Drosophila. Given that Imp-L2 and the human tumor suppressor IGFBP-7 show sequence homology in their carboxy-terminal immunoglobulin-like domains, we suggest that their common precursor was an ancestral insulin-binding protein. http://jbiol.com/content/7/3/10 Basil Honegger, Milos Galic, Katja Köhler, Franz Wittwer, Walter Brogiolo, Ernst Hafen and Hugo Stocker Journal of Biology 2008, 7:10 Number of accesses: 436 2008-04-15 doi:10.1186/jbiol72 Journal of Biology 1475-4924 7 10 2008-04-15 Background: Cell growth underlies many key cellular and developmental processes, yet a limited number of studies have been carried out on cell-growth regulation. Comprehensive studies at the transcriptional, proteomic and metabolic levels under defined controlled conditions are currently lacking. Results: Metabolic control analysis is being exploited in a systems biology study of the eukaryotic cell. Using chemostat culture, we have measured the impact of changes in flux (growth rate) on the transcriptome, proteome, endometabolome and exometabolome of the yeast Saccharomyces cerevisiae. Each functional genomic level shows clear growth-rate-associated trends and discriminates between carbon-sufficient and carbon-limited conditions. Genes consistently and significantly upregulated with increasing growth rate are frequently essential and encode evolutionarily conserved proteins of known function that participate in many protein-protein interactions. In contrast, more unknown, and fewer essential, genes are downregulated with increasing growth rate; their protein products rarely interact with one another. A large proportion of yeast genes under positive growth-rate control share orthologs with other eukaryotes, including humans. Significantly, transcription of genes encoding components of the TOR complex (a major controller of eukaryotic cell growth) is not subject to growth-rate regulation. Moreover, integrative studies reveal the extent and importance of post-transcriptional control, patterns of control of metabolic fluxes at the level of enzyme synthesis, and the relevance of specific enzymatic reactions in the control of metabolic fluxes during cell growth. Conclusion: This work constitutes a first comprehensive systems biology study on growth-rate control in the eukaryotic cell. The results have direct implications for advanced studies on cell growth, in vivo regulation of metabolic fluxes for comprehensive metabolic engineering, and for the design of genome-scale systems biology models of the eukaryotic cell. http://jbiol.com/content/6/2/4 Juan I Castrillo, Leo A Zeef, David C Hoyle, Nianshu Zhang, Andrew Hayes, David CJ Gardner, Michael J Cornell, June Petty, Luke Hakes, Leanne Wardleworth, Bharat Rash, Marie Brown, Warwick B Dunn, David Broadhurst, Kerry O'Donoghue, Svenja S Hester, Tom PJ Dunkley, Sarah R Hart, Neil Swainston, Peter Li, Simon J Gaskell, Norman W Paton, Kathryn S Lilley, Douglas B Kell and Stephen G Oliver Journal of Biology 2007, 6:4 Number of accesses: 419 2007-04-30 doi:10.1186/jbiol54 Journal of Biology 1475-4924 6 4 2007-04-30 Background: The study of complex biological networks and prediction of gene function has been enabled by high-throughput (HTP) methods for detection of genetic and protein interactions. Sparse coverage in HTP datasets may, however, distort network properties and confound predictions. Although a vast number of well substantiated interactions are recorded in the scientific literature, these data have not yet been distilled into networks that enable system-level inference. Results: We describe here a comprehensive database of genetic and protein interactions, and associated experimental evidence, for the budding yeast Saccharomyces cerevisiae, as manually curated from over 31,793 abstracts and online publications. This literature-curated (LC) dataset contains 33,311 interactions, on the order of all extant HTP datasets combined. Surprisingly, HTP protein-interaction datasets currently achieve only around 14% coverage of the interactions in the literature. The LC network nevertheless shares attributes with HTP networks, including scale-free connectivity and correlations between interactions, abundance, localization, and expression. We find that essential genes or proteins are enriched for interactions with other essential genes or proteins, suggesting that the global network may be functionally unified. This interconnectivity is supported by a substantial overlap of protein and genetic interactions in the LC dataset. We show that the LC dataset considerably improves the predictive power of network-analysis approaches. The full LC dataset is available at the BioGRID (http://www.thebiogrid.org) and SGD (http://www.yeastgenome.org/) databases. Conclusion: Comprehensive datasets of biological interactions derived from the primary literature provide critical benchmarks for HTP methods, augment functional prediction, and reveal system-level attributes of biological networks. http://jbiol.com/content/5/4/11 Teresa Reguly, Ashton Breitkreutz, Lorrie Boucher, Bobby-Joe Breitkreutz, Gary C Hon, Chad L Myers, Ainslie Parsons, Helena Friesen, Rose Oughtred, Amy Tong, Chris Stark, Yuen Ho, David Botstein, Brenda Andrews, Charles Boone, Olga G Troyanskya, Trey Ideker, Kara Dolinski, Nizar N Batada and Mike Tyers Journal of Biology 2006, 5:11 Number of accesses: 313 2006-06-08 doi:10.1186/jbiol36 Journal of Biology 1475-4924 5 11 2006-06-08 Background: The dissection of biological pathways and of the molecular basis of disease requires devices to analyze simultaneously a staggering number of protein isoforms in a given cell under given conditions. Such devices face significant challenges, including the identification of probe molecules specific for each protein isoform, protein immobilization techniques with micrometer or submicrometer resolution, and the development of a sensing mechanism capable of very high-density, highly multiplexed detection. Results: We present a novel strategy that offers practical solutions to these challenges, featuring peptide aptamers as artificial protein detectors arrayed on gold electrodes with feature sizes one order of magnitude smaller than existing formats. We describe a method to immobilize specific peptide aptamers on individual electrodes at the micrometer scale, together with a robust and label-free electronic sensing system. As a proving proof of principle experiment, we demonstrate the specific recognition of cyclin-dependent protein kinases in whole-cell lysates using arrays of ten electrodes functionalized with individual peptide aptamers, with no measurable cross-talk between electrodes. The sensitivity is within the clinically relevant range and can detect proteins against the high, whole-cell lysate background. Conclusion: The use of peptide aptamers selected in vivo to recognize specific protein isoforms, the ability to functionalize each microelectrode individually, the electronic nature and scalability of the label-free detection and the scalability of the array fabrication combine to yield the potential for highly multiplexed devices with increasingly small detection areas and higher sensitivities that may ultimately allow the simultaneous monitoring of tens or hundreds of thousands of protein isoforms. http://jbiol.com/content/7/1/3 David Evans, Steven Johnson, Sophie Laurenson, A Giles Davies, Paul Ko Ferrigno and Christoph Wälti Journal of Biology 2008, 7:3 Number of accesses: 310 2008-01-31 doi:10.1186/jbiol62 Journal of Biology 1475-4924 7 3 2008-01-31 Background: The diversity of metazoan cell shapes is influenced by the dynamic cytoskeletal network. With the advent of RNA-interference (RNAi) technology, it is now possible to screen systematically for genes controlling specific cell-biological processes, including those required to generate distinct morphologies. Results: We adapted existing RNAi technology in Drosophila cell culture for use in high-throughput screens to enable a comprehensive genetic dissection of cell morphogenesis. To identify genes responsible for the characteristic shape of two morphologically distinct cell lines, we performed RNAi screens in each line with a set of double-stranded RNAs (dsRNAs) targeting 994 predicted cell shape regulators. Using automated fluorescence microscopy to visualize actin filaments, microtubules and DNA, we detected morphological phenotypes for 160 genes, one-third of which have not been previously characterized in vivo. Genes with similar phenotypes corresponded to known components of pathways controlling cytoskeletal organization and cell shape, leading us to propose similar functions for previously uncharacterized genes. Furthermore, we were able to uncover genes acting within a specific pathway using a co-RNAi screen to identify dsRNA suppressors of a cell shape change induced by Pten dsRNA. Conclusions: Using RNAi, we identified genes that influence cytoskeletal organization and morphology in two distinct cell types. Some genes exhibited similar RNAi phenotypes in both cell types, while others appeared to have cell-type-specific functions, in part reflecting the different mechanisms used to generate a round or a flat cell morphology. http://jbiol.com/content/2/4/27 AA Kiger, B Baum, S Jones, MR Jones, A Coulson, C Echeverri and N Perrimon Journal of Biology 2003, 2:27 Number of accesses: 309 2003-10-01 doi:10.1186/1475-4924-2-27 Journal of Biology 1475-4924 2 27 2003-10-01