440 research outputs found

    Climatic warming destabilizes forest ant communities

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    How will ecological communities change in response to climate warming? Direct effects of temperature and indirect cascading effects of species interactions are already altering the structure of local communities, but the dynamics of community change are still poorly understood. We explore the cumulative effects of warming on the dynamics and turnover of forest ant communities that were warmed as part of a 5-year climate manipulation experiment at two sites in eastern North America. At the community level, warming consistently increased occupancy of nests and decreased extinction and nest abandonment. This consistency was largely driven by strong responses of a subset of thermophilic species at each site. As colonies of thermophilic species persisted in nests for longer periods of time under warmer temperatures, turnover was diminished, and species interactions were likely altered. We found that dynamical (Lyapunov) community stability decreased with warming both within and between sites. These results refute null expectations of simple temperature-driven increases in the activity and movement of thermophilic ectotherms. The reduction in stability under warming contrasts with the findings of previous studies that suggest resilience of species interactions to experimental and natural warming. In the face of warmer, no-analog climates, communities of the future May become increasingly fragile and unstable

    Spatial transcriptomics reveals a role for sensory nerves in preserving cranial suture patency through modulation of BMP/TGF-β signaling

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    : The patterning and ossification of the mammalian skeleton requires the coordinated actions of both intrinsic bone morphogens and extrinsic neurovascular signals, which function in a temporal and spatial fashion to control mesenchymal progenitor cell (MPC) fate. Here, we show the genetic inhibition of tropomyosin receptor kinase A (TrkA) sensory nerve innervation of the developing cranium results in premature calvarial suture closure, associated with a decrease in suture MPC proliferation and increased mineralization. In vitro, axons from peripheral afferent neurons derived from dorsal root ganglions (DRGs) of wild-type mice induce MPC proliferation in a spatially restricted manner via a soluble factor when cocultured in microfluidic chambers. Comparative spatial transcriptomic analysis of the cranial sutures in vivo confirmed a positive association between sensory axons and proliferative MPCs. SpatialTime analysis across the developing suture revealed regional-specific alterations in bone morphogenetic protein (BMP) and TGF-β signaling pathway transcripts in response to TrkA inhibition. RNA sequencing of DRG cell bodies, following direct, axonal coculture with MPCs, confirmed the alterations in BMP/TGF-β signaling pathway transcripts. Among these, the BMP inhibitor follistatin-like 1 (FSTL1) replicated key features of the neural-to-bone influence, including mitogenic and anti-osteogenic effects via the inhibition of BMP/TGF-β signaling. Taken together, our results demonstrate that sensory nerve-derived signals, including FSTL1, function to coordinate cranial bone patterning by regulating MPC proliferation and differentiation in the suture mesenchyme

    High-throughput processing and normalization of one-color microarrays for transcriptional meta-analyses

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    <p>Abstract</p> <p>Background</p> <p>Microarray experiments are becoming increasingly common in biomedical research, as is their deposition in publicly accessible repositories, such as Gene Expression Omnibus (GEO). As such, there has been a surge in interest to use this microarray data for meta-analytic approaches, whether to increase sample size for a more powerful analysis of a specific disease (e.g. lung cancer) or to re-examine experiments for reasons different than those examined in the initial, publishing study that generated them. For the average biomedical researcher, there are a number of practical barriers to conducting such meta-analyses such as manually aggregating, filtering and formatting the data. Methods to automatically process large repositories of microarray data into a standardized, directly comparable format will enable easier and more reliable access to microarray data to conduct meta-analyses.</p> <p>Methods</p> <p>We present a straightforward, simple but robust against potential outliers method for automatic quality control and pre-processing of tens of thousands of single-channel microarray data files. GEO GDS files are quality checked by comparing parametric distributions and quantile normalized to enable direct comparison of expression level for subsequent meta-analyses.</p> <p>Results</p> <p>13,000 human 1-color experiments were processed to create a single gene expression matrix that subsets can be extracted from to conduct meta-analyses. Interestingly, we found that when conducting a global meta-analysis of gene-gene co-expression patterns across all 13,000 experiments to predict gene function, normalization had minimal improvement over using the raw data.</p> <p>Conclusions</p> <p>Normalization of microarray data appears to be of minimal importance on analyses based on co-expression patterns when the sample size is on the order of thousands microarray datasets. Smaller subsets, however, are more prone to aberrations and artefacts, and effective means of automating normalization procedures not only empowers meta-analytic approaches, but aids in reproducibility by providing a standard way of approaching the problem.</p> <p>Data availability: matrix containing normalized expression of 20,813 genes across 13,000 experiments is available for download at . Source code for GDS files pre-processing is available from the authors upon request.</p

    Integrated genomics of susceptibility to alkylator-induced leukemia in mice

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    <p>Abstract</p> <p>Background</p> <p>Therapy-related acute myeloid leukemia (t-AML) is a secondary, generally incurable, malignancy attributable to chemotherapy exposure. Although there is a genetic component to t-AML susceptibility in mice, the relevant loci and the mechanism(s) by which they contribute to t-AML are largely unknown. An improved understanding of susceptibility factors and the biological processes in which they act may lead to the development of t-AML prevention strategies.</p> <p>Results</p> <p>In this work we applied an integrated genomics strategy in inbred strains of mice to find novel factors that might contribute to susceptibility. We found that the pre-exposure transcriptional state of hematopoietic stem/progenitor cells predicts susceptibility status. More than 900 genes were differentially expressed between susceptible and resistant strains and were highly enriched in the apoptotic program, but it remained unclear which genes, if any, contribute directly to t-AML susceptibility. To address this issue, we integrated gene expression data with genetic information, including single nucleotide polymorphisms (SNPs) and DNA copy number variants (CNVs), to identify genetic networks underlying t-AML susceptibility. The 30 t-AML susceptibility networks we found are robust: they were validated in independent, previously published expression data, and different analytical methods converge on them. Further, the networks are enriched in genes involved in cell cycle and DNA repair (pathways not discovered in traditional differential expression analysis), suggesting that these processes contribute to t-AML susceptibility. Within these networks, the putative regulators (e.g., <it>Parp2</it>, <it>Casp9</it>, <it>Polr1b</it>) are the most likely to have a non-redundant role in the pathogenesis of t-AML. While identifying these networks, we found that current CNVR and SNP-based haplotype maps in mice represented distinct sources of genetic variation contributing to expression variation, implying that mapping studies utilizing either source alone will have reduced sensitivity.</p> <p>Conclusion</p> <p>The identification and prioritization of genes and networks not previously implicated in t-AML generates novel hypotheses on the biology and treatment of this disease that will be the focus of future research.</p

    Mental Health Problems among Children One-Year after Sichuan Earthquake in China: A Follow-up Study

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    Background: On May 12, 2008, a destructive earthquake registering 8.0 on the Richter scale struck Sichuan Province, southwest China. Beichuan County was the epicenter which was one of the areas nearly completely destroyed by the earthquake. In Beichuan, about 15000 people died and 3000 people were missing. Specially, the earthquake took 1587 students&#39; and 214 teachers&#39; lives from the elementary and middle schools there. The main purpose of the study was to provide a better understanding of mental health problems and associated risk factors among children after earthquake

    International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

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    In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

    Copy-number-variation and copy-number-alteration region detection by cumulative plots

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    Background: Regions with copy number variations (in germline cells) or copy number alteration (in somatic cells) are of great interest for human disease gene mapping and cancer studies. They represent a new type of mutation and are larger-scaled than the single nucleotide polymorphisms. Using genotyping microarray for copy number variation detection has become standard, and there is a need for improving analysis methods. Results: We apply the cumulative plot to the detection of regions with copy number variation/alteration, on samples taken from a chronic lymphocytic leukemia patient. Two sets of whole-genome genotyping of 317k single nucleotide polymorphisms, one from the normal cell and another from the cancer cell, are analyzed. We demonstrate the utility of cumulative plot in detecting a 9Mb (9 x 10^6 bases) hemizygous deletion and 1Mb homozygous deletion on chromosome 13. We also show the possibility to detect smaller copy number variation/alteration regions below the 100kb range. Conclusions: As a graphic tool, the cumulative plot is an intuitive and a scale-free (window-less) way for detecting copy number variation/alteration regions, especially when such regions are small

    Medicine in words and numbers: a cross-sectional survey comparing probability assessment scales

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    Contains fulltext : 56355.pdf ( ) (Open Access)Background / In the complex domain of medical decision making, reasoning under uncertainty can benefit from supporting tools. Automated decision support tools often build upon mathematical models, such as Bayesian networks. These networks require probabilities which often have to be assessed by experts in the domain of application. Probability response scales can be used to support the assessment process. We compare assessments obtained with different types of response scale. Methods / General practitioners (GPs) gave assessments on and preferences for three different probability response scales: a numerical scale, a scale with only verbal labels, and a combined verbal-numerical scale we had designed ourselves. Standard analyses of variance were performed. Results / No differences in assessments over the three response scales were found. Preferences for type of scale differed: the less experienced GPs preferred the verbal scale, the most experienced preferred the numerical scale, with the groups in between having a preference for the combined verbal-numerical scale. Conclusion / We conclude that all three response scales are equally suitable for supporting probability assessment. The combined verbal-numerical scale is a good choice for aiding the process, since it offers numerical labels to those who prefer numbers and verbal labels to those who prefer words, and accommodates both more and less experienced professionals.8 p

    Delamination technique together with longitudinal incisions for treatment of Chiari I/syringomyelia complex: a prospective clinical study

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    <p>Abstract</p> <p>Background</p> <p>Treatment modalities in Chiari malformation type 1(CMI) accompanied by syringomyelia have not yet been standardized. Pathologies such as a small posterior fossa and thickened dura mater have been discussed previously. Various techniques have been explored to enlarge the foramen magnum and to expand the dura. The aim of this clinical study was to explore a new technique of excision of the external dura accompanied by widening the cisterna magna and making longitudinal incisions in the internal dura, without disturbing the arachnoid.</p> <p>Methods</p> <p>Ten patients with CMI and syringomyelia, operated between 2004 and 2006, formed this prospective series. All cases underwent foramen magnum decompression of 3 × 3 cm area with C1–C2 (partial) laminectomy, resection of foramen magnum fibrous band, excision of external dura, delamination and widening of internal dura with longitudinal incisions.</p> <p>Results</p> <p>Patients were aged between 25 and 58 years and occipital headache was the most common complaint. The mean duration of preoperative symptoms was 4 years and the follow-up time was 25 months. Clinical progression was halted for all patients; eight patients completely recovered and two reported no change. In one patient, there was a transient cerebrospinal fluid (CSF) fistula that was treated with tissue adhesive. While syringomyelia persisted radiologically with radiological stability in five patients; for three patients the syringomyelic cavity decreased in size, and for the remaining two it regressed completely.</p> <p>Conclusion</p> <p>Removal of the fibrous band and the outer dural layer, at level of foramen magnum, together with the incision of inner dural layer appears to be good technique in adult CMI patients. The advantages are short operation time, no need for duraplasty, sufficient posterior fossa decompression, absence of CSF fistulas as a result of extra arachnoidal surgery, and short duration of hospitalization. Hence this surgical technique has advantages compared to other techniques.</p
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