http://www.biomedcentral.com/bmcbiol/ The latest research articles published by BMC Biology 2009-11-23T00:00:00Z 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/ Background: Subjective tinnitus is the perception of a sound in the absence of any physical source. It has been shown that tinnitus is associated with hyperactivity of the auditory cortices. Accompanying this hyperactivity, changes in non-auditory brain structures have also been reported. However, there have been no studies on the long-range information flow between these regions. Results: Using Magnetoencephalography, we investigated the long-range cortical networks of chronic tinnitus sufferers (n = 23) and healthy controls (n = 24) in the resting state. A beamforming technique was applied to reconstruct the brain activity at source level and the directed functional coupling between all voxels was analyzed by means of Partial Directed Coherence. Within a cortical network, hubs are brain structures that either influence a great number of other brain regions or that are influenced by a great number of other brain regions. By mapping the cortical hubs in tinnitus and controls we report fundamental group differences in the global networks, mainly in the gamma frequency range. The prefrontal cortex, the orbitofrontal cortex and the parieto-occipital region were core structures in this network. The information flow from the global network to the temporal cortex correlated positively with the strength of tinnitus distress. Conclusion: With the present study we suggest that the hyperactivity of the temporal cortices in tinnitus is integrated in a global network of long-range cortical connectivity. Top-down influence from the global network on the temporal areas relates to the subjective strength of the tinnitus distress. http://www.biomedcentral.com/1741-7007/7/80 Winfried Schlee Nadia Mueller Thomas Hartmann Julian Keil Isabel Lorenz Nathan Weisz BMC Biology 2009, 7:80 2009-11-23T00:00:00Z doi:10.1186/1741-7007-7-80 BMC Biology 1741-7007 7 80 2009-11-23T00:00:00Z PDF Background: Early microbial colonization of the gut reduces the incidence of infectious, inflammatory and autoimmune diseases. Recent population studies reveal that childhood hygiene is a significant risk factor for development of inflammatory bowel disease, thereby reinforcing the hygiene hypothesis and the potential importance of microbial colonization during early life. The extent to which early-life environment impacts on microbial diversity of the adult gut and subsequent immune processes has not been comprehensively investigated thus far. We addressed this important question using the pig as a model to evaluate the impact of early-life environment on microbe/host gut interactions during development. Results: Genetically-related piglets were housed in either indoor or outdoor environments or in experimental isolators. Analysis of over 3,000 16S rRNA sequences revealed major differences in mucosa-adherent microbial diversity in the ileum of adult pigs attributable to differences in early-life environment. Pigs housed in a natural outdoor environment showed a dominance of Firmicutes, in particular Lactobacillus, whereas animals housed in a hygienic indoor environment had reduced Lactobacillus and higher numbers of potentially pathogenic phylotypes. Our analysis revealed a strong negative correlation between the abundance of Firmicutes and pathogenic bacterial populations in the gut. These differences were exaggerated in animals housed in experimental isolators. Affymetrix microarray technology and Real-time Polymerase Chain Reaction revealed significant gut-specific gene responses also related to early-life environment. Significantly, indoor-housed pigs displayed increased expression of Type 1 interferon genes, Major Histocompatibility Complex class I and several chemokines. Gene Ontology and pathway analysis further confirmed these results. Conclusions: Early-life environment significantly affects both microbial composition of the adult gut and mucosal innate immune function. We observed that a microbiota dominated by lactobacilli may function to maintain mucosal immune homeostasis and limit pathogen colonization. http://www.biomedcentral.com/1741-7007/7/79 Imke Mulder Bettina Schmidt Christopher Stokes Marie Lewis Mick Bailey Rustam Aminov James Prosser Bhupinder Gill John Pluske Claus-Dieter Mayer Corran Musk Denise Kelly BMC Biology 2009, 7:79 2009-11-20T00:00:00Z doi:10.1186/1741-7007-7-79 BMC Biology 1741-7007 7 79 2009-11-20T00:00:00Z PDF Background: Phylogeographic reconstruction of some bacterial populations is hindered by low diversity coupled with high levels of lateral gene transfer. A comparison of recombination levels and diversity at seven housekeeping genes for eleven bacterial species, most of which are commonly cited as having high levels of lateral gene transfer shows that the relative contributions of homologous recombination versus mutation for Burkholderia pseudomallei is over two times higher than for Streptococcus pneumoniae and is thus the highest value yet reported in bacteria. Despite the potential for homologous recombination to increase diversity, B. pseudomallei exhibits a relative lack of diversity at these loci. In these situations, whole genome genotyping of orthologous shared single nucleotide polymorphism loci, discovered using next generation sequencing technologies, can provide very large data sets capable of estimating core phylogenetic relationships. We compared and searched 43 whole genome sequences of B. pseudomallei and its closest relatives for single nucleotide polymorphisms in orthologous shared regions to use in phylogenetic reconstruction. Results: Bayesian phylogenetic analyses of >14,000 single nucleotide polymorphisms yielded completely resolved trees for these 43 strains with high levels of statistical support. These results enable a better understanding of a separate analysis of population differentiation among >1,700 B. pseudomallei isolates as defined by sequence data from seven housekeeping genes. We analyzed this larger data set for population structure and allele sharing that can be attributed to lateral gene transfer. Our results suggest that despite an almost panmictic population, we can detect two distinct populations of B. pseudomallei that conform to biogeographic patterns found in many plant and animal species. That is, separation along Wallace's Line, a biogeographic boundary between Southeast Asia and Australia. Conclusions: We describe an Australian origin for B. pseudomallei, characterized by a single introduction event into Southeast Asia during a recent glacial period, and variable levels of lateral gene transfer within populations. These patterns provide insights into mechanisms of genetic diversification in B. pseudomallei and its closest relatives, and provide a framework for integrating the traditionally separate fields of population genetics and phylogenetics for other bacterial species with high levels of lateral gene transfer. http://www.biomedcentral.com/1741-7007/7/78 Talima Pearson Philip Giffard Stephen Beckstrom-Sternberg Raymond Auerbach Heidie Hornstra Apichai Tuanyok Erin Price Mindy Glass Benjamin Leadem James Beckstrom-Sternberg Gerard Allan Jeffrey Foster David Wagner Richard Okinaka Siew Hoon Sim Ofori Pearson Zaining Wu Jean Chang Rajinder Kaul Alex Hoffmaster Thomas Brettin Richard Robison Mark Mayo Jay Gee Patrick Tan Bart Currie Paul Keim BMC Biology 2009, 7:78 2009-11-18T00:00:00Z doi:10.1186/1741-7007-7-78 BMC Biology 1741-7007 7 78 2009-11-18T00:00:00Z PDF Background: Basoapical polarity in epithelia is critical for proper tissue function, and control of proliferation and survival. Cell culture models that recapitulate epithelial tissue architecture are invaluable to unravel developmental and disease mechanisms. Although factors important for the establishment of basal polarity have been identified, requirements for the formation of apical polarity in three-dimensional tissue structures have not been thoroughly investigated. Results: We demonstrate that the human mammary epithelial cell line-3522 S1, provides a resilient model for studying the formation of basoapical polarity in glandular structures. Testing three-dimensional culture systems that differ in composition and origin of substrata reveals that apical polarity is more sensitive to culture conditions than basal polarity. Using a new high-throughput culture method that produces basoapical polarity in glandular structures without a gel coat, we show that basal polarity-mediated signaling and collagen IV are both necessary for the development of apical polarity. Conclusions: These results provide new insights into the role of the basement membrane, and especially collagen IV, in the development of the apical pole, a critical element of the architecture of glandular epithelia. Also, the high-throughput culture method developed in this study should open new avenues for high-content screening of agents that act on mammary tissue homeostasis and thus, on architectural changes involved in cancer development. http://www.biomedcentral.com/1741-7007/7/77 Cedric Plachot Lesley Chaboub Hibret Adissu Lei Wang Albert Urazaev Jennifer Sturgis Elikplimi Asem Sophie Lelievre BMC Biology 2009, 7:77 2009-11-16T00:00:00Z doi:10.1186/1741-7007-7-77 BMC Biology 1741-7007 7 77 2009-11-16T00:00:00Z PDF Background: The signal recognition particle (SRP) receptor plays a vital role in co-translational protein targeting, because it connects the soluble SRP-ribosome-nascent chain complex (SRP-RNCs) to the membrane bound Sec translocon. The eukaryotic SRP receptor (SR) is a heterodimeric protein complex, consisting of two unrelated GTPases. The SRβ subunit is an integral membrane protein, which tethers the SRP-interacting SRα subunit permanently to the endoplasmic reticulum membrane. The prokaryotic SR lacks the SRβ subunit and consists of only the SRα homologue FtsY. Strikingly, although FtsY requires membrane contact for functionality, cell fractionation studies have localized FtsY predominantly to the cytosolic fraction of Escherichia coli. So far, the exact function of the soluble SR in E. coli is unknown, but it has been suggested that, in contrast to eukaryotes, the prokaryotic SR might bind SRP-RNCs already in the cytosol and only then initiates membrane targeting. Results: In the current study we have determined the contribution of soluble FtsY to co-translational targeting in vitro and have re-analysed the localization of FtsY in vivo by fluorescence microscopy. Our data show that FtsY can bind to SRP-ribosome nascent chains (RNCs) in the absence of membranes. However, these soluble FtsY-SRP-RNC complexes are not efficiently targeted to the membrane. In contrast, we observed effective targeting of SRP-RNCs to membrane-bond FtsY. These data show that soluble FtsY does not contribute significantly to cotranslational targeting in E. coli. In agreement with this observation, our in vivo analyses of FtsY localization in bacterial cells by fluorescence microscopy revealed that the vast majority of FtsY was localized to the inner membrane and that soluble FtsY constituted only a negligible species in vivo. Conclusion: The exact function of the SRP receptor (SR) in bacteria has so far been enigmatic. Our data show that the bacterial SR is almost exclusively membrane-bound in vivo, indicating that the presence of a soluble SR is probably an artefact of cell fractionation. Thus, co-translational targeting in bacteria does not involve the formation of a soluble SR-signal recognition particle (SRP)-ribosome nascent chain (RNC) intermediate but requires membrane contact of FtsY for efficient SRP-RNC recruitment. http://www.biomedcentral.com/1741-7007/7/76 Miryana Mircheva Diana Boy Benjamin Weiche Friederike Hucke Peter Graumann Hans-Georg Koch BMC Biology 2009, 7:76 2009-11-13T00:00:00Z doi:10.1186/1741-7007-7-76 BMC Biology 1741-7007 7 76 2009-11-13T00:00:00Z XML Background: Ubiquitin regulates a myriad of important cellular processes through covalent attachment to its substrates. A classic role for ubiquitin is to flag proteins for destruction by the proteasome. Recent studies indicate that ubiquitin-binding proteins (e.g. Rad23, Dsk2, Rpn10) play a pivotal role in transferring ubiquitylated proteins to the proteasome. However, the specific role of these ubiquitin receptors remains poorly defined. A key to unraveling the functions of these ubiquitin receptors is to identify their cellular substrates and biological circuits they are involved in. Although many strategies have been developed for substrate isolation, the identification of physiological targets of proteolytic pathways has proven to be quite challenging. Results: Using a genome-wide functional screen, we have identified 11 yeast genes that cause slower growth upon their overexpression in cells lacking two ubiquitin-binding proteins Rad23 and Dsk2. Our results suggest that proper functioning of Rad23 and Dsk2 is required for efficient pheromone response, transcription, amino acid metabolism, and DNA damage response. Two proteins identified by the screen are shown to be proteolytic substrates of Dsk2, validating the large scale synthetic dosage lethality screen as a new strategy for identifying substrates of a specific degradation pathway. Conclusion: In conclusion, as proof-of-concept, we show that a synthetic dosage lethality screen, which is based on the toxicity induced by gene overexpression, offers an effective, complementary method to elucidating biological functions of proteolytic pathways. http://www.biomedcentral.com/1741-7007/7/75 Chang Liu Dewald van Dyk Yue Li Brenda Andrews Hai Rao BMC Biology 2009, 7:75 2009-11-12T00:00:00Z doi:10.1186/1741-7007-7-75 BMC Biology 1741-7007 7 75 2009-11-12T00:00:00Z XML Background: Bone-eating Osedax worms have proved to be surprisingly diverse and widespread. Including the initial description of this genus in 2004, five species that live at depths between 25 and 3,000 m in the eastern and western Pacific and in the north Atlantic have been named to date. Here, we provide molecular and morphological evidence for 12 additional evolutionary lineages from Monterey Bay, California. To assess their phylogenetic relationships and possible status as new undescribed species, we examined DNA sequences from two mitochondrial (COI and 16S rRNA) and three nuclear genes (H3, 18S and 28S rRNA). Results: Phylogenetic analyses identified 17 distinct evolutionary lineages. Levels of sequence divergence among the undescribed lineages were similar to those found among the named species. The 17 lineages clustered into five well-supported clades that also differed for a number of key morphological traits. Attempts to determine the evolutionary age of Osedax depended on prior assumptions about nucleotide substitution rates. According to one scenario involving a molecular clock calibrated for shallow marine invertebrates, Osedax split from its siboglinid relatives about 45 million years ago when archeocete cetaceans first appeared and then diversified during the late Oligocene and early Miocene when toothed and baleen whales appeared. Alternatively, the use of a slower clock calibrated for deep-sea annelids suggested that Osedax split from its siboglinid relatives during the Cretaceous and began to diversify during the Early Paleocene, at least 20 million years before the origin of large marine mammals. Conclusion: To help resolve uncertainties about the evolutionary age of Osedax, we suggest that the fossilized bones from Cretaceous marine reptiles and late Oligocene cetaceans be examined for possible trace fossils left by Osedax roots. Regardless of the outcome, the present molecular evidence for strong phylogenetic concordance across five separate genes suggests that the undescribed Osedax lineages comprise evolutionarily significant units that have been separate from one another for many millions of years. These data coupled with ongoing morphological analyses provide a solid foundation for their future descriptions as new species. http://www.biomedcentral.com/1741-7007/7/74 Robert Vrijenhoek Shannon Johnson Greg Rouse BMC Biology 2009, 7:74 2009-11-10T00:00:00Z doi:10.1186/1741-7007-7-74 BMC Biology 1741-7007 7 74 2009-11-10T00:00:00Z XML Background: Given its sequenced genome and efficient systemic RNA interference response, the red flour beetle Tribolium castaneum is a model organism well suited for reverse genetics. Even so, there is a pressing need for forward genetic analysis to escape the bias inherent in candidate gene approaches. Results: To produce easy-to-maintain insertional mutations and to obtain fluorescent marker lines to aid phenotypic analysis, we undertook a large-scale transposon mutagenesis screen. In this screen, we produced more than 6,500 new piggyBac insertions. Of these, 421 proved to be recessive lethal, 75 were semi-lethal, and eight indicated recessive sterility, while 505 showed new enhancer-trap patterns. Insertion junctions were determined for 403 lines and often appeared to be located within transcription units. Insertion sites appeared to be randomly distributed throughout the genome, with the exception of a preference for reinsertion near the donor site. Conclusion: A large collection of enhancer-trap and embryonic lethal beetle lines has been made available to the research community and will foster investigations into diverse fields of insect biology, pest control, and evolution. Because the genetic elements used in this screen are species-nonspecific, and because the crossing scheme does not depend on balancer chromosomes, the methods presented herein should be broadly applicable for many insect species. http://www.biomedcentral.com/1741-7007/7/73 Jochen Trauner Johannes Schinko Marce Lorenzen Teresa Shippy Ernst Wimmer Richard Beeman Martin Klingler Gregor Bucher Susan Brown BMC Biology 2009, 7:73 2009-11-05T00:00:00Z doi:10.1186/1741-7007-7-73 BMC Biology 1741-7007 7 73 2009-11-05T00:00:00Z XML Background: Recent advances in sequencing strategies make possible unprecedented depth and scale of sampling for molecular detection of microbial diversity. Two major paradigm-shifting discoveries include the detection of bacterial diversity that is one to two orders of magnitude greater than previous estimates, and the discovery of an exciting 'rare biosphere' of molecular signatures ('species') of poorly understood ecological significance. We applied a high-throughput parallel tag sequencing (454 sequencing) protocol adopted for eukaryotes to investigate protistan community complexity in two contrasting anoxic marine ecosystems (Framvaren Fjord, Norway; Cariaco deep-sea basin, Venezuela). Both sampling sites have previously been scrutinized for protistan diversity by traditional clone library construction and Sanger sequencing. By comparing these clone library data with 454 amplicon library data, we assess the efficiency of high-throughput tag sequencing strategies. We here present a novel, highly conservative bioinformatic analysis pipeline for the processing of large tag sequence data sets. Results: The analyses of ca. 250,000 sequence reads revealed that the number of detected Operational Taxonomic Units (OTUs) far exceeded previous richness estimates from the same sites based on clone libraries and Sanger sequencing. More than 90% of this diversity was represented by OTUs with less than 10 sequence tags. We detected a substantial number of taxonomic groups like Apusozoa, Chrysomerophytes, Centroheliozoa, Eustigmatophytes, hyphochytriomycetes, Ichthyosporea, Oikomonads, Phaeothamniophytes, and rhodophytes which remained undetected by previous clone library-based diversity surveys of the sampling sites. The most important innovations in our newly developed bioinformatics pipeline employ (i) BLASTN with query parameters adjusted for highly variable domains and a complete database of public ribosomal RNA (rRNA) gene sequences for taxonomic assignments of tags; (ii) a clustering of tags at k differences (Levenshtein distance) with a newly developed algorithm enabling very fast OTU clustering for large tag sequence data sets; and (iii) a novel parsing procedure to combine the data from individual analyses. Conclusion: Our data highlight the magnitude of the under-sampled 'protistan gap' in the eukaryotic tree of life. This study illustrates that our current understanding of the ecological complexity of protist communities, and of the global species richness and genome diversity of protists, is severely limited. Even though 454 pyrosequencing is not a panacea, it allows for more comprehensive insights into the diversity of protistan communities, and combined with appropriate statistical tools, enables improved ecological interpretations of the data and projections of global diversity. http://www.biomedcentral.com/1741-7007/7/72 Thorsten Stoeck Anke Behnke Richard Christen Linda Amaral-Zettler Maria Rodriguez-Mora Andrei Chistoserdov William Orsi Virginia Edgcomb BMC Biology 2009, 7:72 2009-11-03T00:00:00Z doi:10.1186/1741-7007-7-72 BMC Biology 1741-7007 7 72 2009-11-03T00:00:00Z XML Background: Ants form highly social and cooperative colonies that compete, and often fight, against other such colonies, both intra- and interspecifically. Some invasive ants take sociality to an extreme, forming geographically massive 'supercolonies' across thousands of kilometres. The success of social insects generally, as well as invasive ants in particular, stems from the sophisticated mechanisms used to accurately and precisely distinguish colonymates from non-colonymates. Surprisingly, however, the specific chemicals used for this recognition are virtually undescribed. Results: Here, we report the discovery, chemical synthesis and behavioural testing of the colonymate recognition cues used by the widespread and invasive Argentine ant (Linepithema humile). By synthesizing pure versions of these chemicals in the laboratory and testing them in behavioural assays, we show that these compounds trigger aggression among normally amicable nestmates, but control hydrocarbons do not. Furthermore, behavioural testing across multiple different supercolonies reveals that the reaction to individual compounds varies from colony to colony -- the expected reaction to true colony recognition labels. Our results also show that both quantitative and qualitative changes to cuticular hydrocarbon profiles can trigger aggression among nestmates. These data point the way for the development of new environmentally-friendly control strategies based on the species-specific manipulation of aggressive behaviour. Conclusion: Overall, our findings reveal the identity of specific chemicals used for colonymate recognition by the invasive Argentine ants. Although the particular chemicals used by other ants may differ, the patterns reported here are likely to be true for ants generally. As almost all invasive ants display widespread unicoloniality in their introduced ranges, our findings are particularly relevant for our understanding of the biology of these damaging invaders. http://www.biomedcentral.com/1741-7007/7/71 Miriam Brandt Ellen van Wilgenburg Robert Sulc Kenneth Shea Neil Tsutsui BMC Biology 2009, 7:71 2009-10-28T00:00:00Z doi:10.1186/1741-7007-7-71 BMC Biology 1741-7007 7 71 2009-10-28T00:00:00Z XML