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The most accessed research articles published by BioMed Central

  • After the gold rush
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  • Love thy neighbour: facilitation through an alternative signalling modality in plants
    Background: Both competitive and facilitative interactions between species play a fundamental role in shaping natural communities. A recent study showed that competitive interactions between plants can be mediated by some alternative signalling channel, extending beyond those channels studied so far (i.e. chemicals, contact and light). Here, we tested whether such alternative pathway also enables facilitative interactions between neighbouring plant species. Specifically, we examined whether the presence of a ‘good’ neighbouring plant like basil positively influenced the germination of chilli seeds when all known signals were blocked. For this purpose, we used a custom-designed experimental set-up that prevented above- and below-ground contact and blocked chemical and light-mediated signals normally exchange by plants. Results: We found that seed germination was positively enhanced by the presence of a ‘good’ neighbour, even when the known signalling modalities were blocked, indicating that light, touch or chemical signals may not be indispensible for different plant species to sense each other’s presence. Conclusions: We propose that this alternative signalling modality operates as a general indicator of the presence of heterospecifics, enabling seeds to detect and identify a neighbour prior to engaging in a more finely-tuned, but potentially more costly, response.

  • A phylogeny and revised classification of Squamata, including 4161 species of lizards and snakes
    Background: The extant squamates (>9400 known species of lizards and snakes) are one of the most diverse and conspicuous radiations of terrestrial vertebrates, but no studies have attempted to reconstruct a phylogeny for the group with large-scale taxon sampling. Such an estimate is invaluable for comparative evolutionary studies, and to address their classification. Here, we present the first large-scale phylogenetic estimate for Squamata. Results: The estimated phylogeny contains 4161 species, representing all currently recognized families and subfamilies. The analysis is based on up to 12896 base pairs of sequence data per species (average = 2497 bp) from 12 genes, including seven nuclear loci (BDNF, c-mos, NT3, PDC, R35, RAG-1, and RAG-2), and five mitochondrial genes (12S, 16S, cytochrome b, ND2, and ND4). The tree provides important confirmation for recent estimates of higher-level squamate phylogeny based on molecular data (but with more limited taxon sampling), estimates that are very different from previous morphology-based hypotheses. The tree also includes many relationships that differ from previous molecular estimates and many that differ from traditional taxonomy. Conclusions: We present a new large-scale phylogeny of squamate reptiles that should be a valuable resource for future comparative studies. We also present a revised classification of squamates at the family and subfamily level to bring the taxonomy more in line with the new phylogenetic hypothesis. This classification includes new, resurrected, and modified subfamilies within gymnophthalmid and scincid lizards and boid, colubrid, and lamprophiid snakes.

  • Raymond Gosling: the man who crystallized genes
    On April 25th 1953, three publications in Nature forever changed the face of the life sciences in reporting the structure of DNA. Sixty years later, Raymond Gosling shares his memories of the race to the double helix.

  • TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions
    TopHat is a popular spliced aligner for RNA-seq experiments. Here, we describe TopHat2, which incorporates many significant enhancements to TopHat. TopHat2 can align reads of various lengths produced by the latest sequencing technologies, while allowing for variable-length indels with respect to the reference genome. In addition to de novo spliced alignment, TopHat2 can align reads across fusion breaks, which occur after genomic translocations. TopHat2 combines the ability to discover novel splice sites with direct mapping to known transcripts, producing sensitive and accurate alignments, even for highly repetitive genomes or in the presence of pseudogenes. TopHat2 is available at http://ccb.jhu.edu/software/tophat.

  • Management of bleeding and coagulopathy following major trauma: an updated European guideline
    IntroductionEvidence-based recommendations are needed to guide the acute management of the bleeding trauma patient, which when implemented may improve patient outcomes. Methods: The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document represents an updated version of the guideline published by the group in 2007 and updated in 2010. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature. Results: Key changes encompassed in this version of the guideline include new recommendations on the appropriate use of vasopressors and inotropic agents, and reflects an awareness of the growing number of patients in the population at large treated with antiplatelet agents and/or oral anticoagulants. The current guideline also includes recommendations and a discussion of thromboprophylactic strategies for all patients following traumatic injury. The most significant addition is a new section that discusses the need for every institution to develop, implement and adhere to an evidence-based clinical protocol to manage traumatically injured patients. The remaining recommendations have been re-evaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies. Conclusions: A comprehensive, multidisciplinary approach to trauma care and mechanisms with which to ensure that established protocols are consistently implemented will ensure a uniform and high standard of care across Europe and beyond.

  • Meat consumption and mortality - results from the European Prospective Investigation into Cancer and Nutrition
    Background: Recently, some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians. The aim of this study was to examine the association of red meat, processed meat, and poultry consumption with the risk of early death in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: Included in the analysis were 448,568 men and women without prevalent cancer, stroke, or myocardial infarction, and with complete information on diet, smoking, physical activity and body mass index, who were between 35 and 69 years old at baseline. Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality. Results: As of June 2009, 26,344 deaths were observed. After multivariate adjustment, a high consumption of red meat was related to higher all-cause mortality (hazard ratio (HR) = 1.14, 95% confidence interval (CI) 1.01 to 1.28, 160+ versus 10 to 19.9 g/day), and the association was stronger for processed meat (HR = 1.44, 95% CI 1.24 to 1.66, 160+ versus 10 to 19.9 g/day). After correction for measurement error, higher all-cause mortality remained significant only for processed meat (HR = 1.18, 95% CI 1.11 to 1.25, per 50 g/d). We estimated that 3.3% (95% CI 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day. Significant associations with processed meat intake were observed for cardiovascular diseases, cancer, and 'other causes of death'. The consumption of poultry was not related to all-cause mortality. Conclusions: The results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.

  • Nutrient timing revisited: is there a post-exercise anabolic window?
    Nutrient timing is a popular nutritional strategy that involves the consumption of combinations of nutrients--primarily protein and carbohydrate--in and around an exercise session. Some have claimed that this approach can produce dramatic improvements in body composition. It has even been postulated that the timing of nutritional consumption may be more important than the absolute daily intake of nutrients. The post-exercise period is widely considered the most critical part of nutrient timing. Theoretically, consuming the proper ratio of nutrients during this time not only initiates the rebuilding of damaged muscle tissue and restoration of energy reserves, but it does so in a supercompensated fashion that enhances both body composition and exercise performance. Several researchers have made reference to an anabolic “window of opportunity” whereby a limited time exists after training to optimize training-related muscular adaptations. However, the importance - and even the existence - of a post-exercise ‘window’ can vary according to a number of factors. Not only is nutrient timing research open to question in terms of applicability, but recent evidence has directly challenged the classical view of the relevance of post-exercise nutritional intake with respect to anabolism. Therefore, the purpose of this paper will be twofold: 1) to review the existing literature on the effects of nutrient timing with respect to post-exercise muscular adaptations, and; 2) to draw relevant conclusions that allow practical, evidence-based nutritional recommendations to be made for maximizing the anabolic response to exercise.

  • Gene expression analysis of Drosophila Manf mutants reveals perturbations in membrane traffic and major metabolic changes
    Background: MANF and CDNF are evolutionarily conserved neurotrophic factors that specifically support dopaminergic neurons. To date, the receptors and signalling pathways of this novel MANF/CDNF family have remained unknown. Independent studies have showed upregulation of MANF by unfolded protein response (UPR). To enlighten the role of MANF in multicellular organism development we carried out a microarray-based analysis of the transcriptional changes induced by the loss and overexpression of Drosophila Manf. Results: The most dramatic change of expression was observed with genes coding membrane transport proteins and genes related to metabolism. When evaluating in parallel the ultrastructural data and transcriptome changes of maternal/zygotic and only zygotic Manf mutants, the endoplasmic reticulum (ER) stress and membrane traffic alterations were evident. In Drosophila Manf mutants the expression of several genes involved in Parkinson's disease (PD) was altered as well. Conclusions: We conclude that besides a neurotrophic factor, Manf is an important cellular survival factor needed to overcome the UPR especially in tissues with high secretory function. In the absence of Manf, the expression of genes involved in membrane transport, particularly exocytosis and endosomal recycling pathway was altered. In neurodegenerative diseases, such as PD, correct protein folding and proteasome function as well as neurotransmitter synthesis and uptake are crucial for the survival of neurons. The degeneration of dopaminergic neurons is the hallmark for PD and our work provides a clue on the mechanisms by which the novel neurotrophic factor MANF protects these neurons.

  • scribble mutants promote aPKC and JNK-dependent epithelial neoplasia independently of Crumbs
    Background: Metastatic neoplasias are characterized by excessive cell proliferation and disruptions to apico-basal cell polarity and tissue architecture. Understanding how alterations in cell polarity can impact upon tumour development is, therefore, a central issue in cancer biology. The Drosophila gene scribble (scrib) encodes a PDZ-domain scaffolding protein that regulates cell polarity and acts as a tumour suppressor in flies. Increasing evidence also implicates the loss of human Scrib in cancer. In this report, we investigate how loss of Scrib promotes epithelial tumourigenesis in Drosophila, both alone and in cooperation with oncogenic mutations. Results: We find that genetically distinct atypical protein kinase C (aPKC)-dependent and Jun N-terminal kinase (JNK)-dependent alterations in scrib mutants drive epithelial tumourigenesis. First, we show that over-expression of the apical cell polarity determinants Crumbs (Crb) or aPKC induces similar cell morphology defects and over-proliferation phenotypes as scrib loss-of-function. However, the morphological and proliferative defects in scrib mutants are independent of Crb function, and instead can be rescued by a dominant negative (kinase dead) aPKC transgene. Secondly, we demonstrate that loss of Scrib promotes oncogene-mediated transformation through both aPKC and JNK-dependent pathways. JNK normally promotes apoptosis of scrib mutant cells. However, in cooperation with oncogenic activated Ras or Notch signalling, JNK becomes an essential driver of tumour overgrowth and invasion. aPKC-dependent signalling in scrib mutants cooperates with JNK to significantly enhance oncogene-mediated tumour overgrowth. Conclusion: These results demonstrate distinct aPKC and JNK-dependent pathways through which loss of Scrib promotes tumourigenesis in Drosophila. This is likely to have a direct relevance to the way in which human Scrib can similarly restrain an oncogene-mediated transformation and, more generally, on how the outcome of oncogenic signalling can be profoundly perturbed by defects in apico-basal epithelial cell polarity.