391 research outputs found

    Fregene: Simulation of realistic sequence-level data in populations and ascertained samples

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    Background: FREGENE simulates sequence-level data over large genomic regions in large populations. Because, unlike coalescent simulators, it works forwards through time, it allows complex scenarios of selection, demography, and recombination to be modelled simultaneously. Detailed tracking of sites under selection is implemented in FREGENE and provides the opportunity to test theoretical predictions and gain new insights into mechanisms of selection. We describe here main functionalities of both FREGENE and SAMPLE, a companion program that can replicate association study datasets.Results: We report detailed analyses of six large simulated datasets that we have made publicly available. Three demographic scenarios are modelled: one panmictic, one substructured with migration, and one complex scenario that mimics the principle features of genetic variation in major worldwide human populations. For each scenario there is one neutral simulation, and one with a complex pattern of selection.Conclusion: FREGENE and the simulated datasets will be valuable for assessing the validity of models for selection, demography and population genetic parameters, as well as the efficacy of association studies. Its principle advantages are modelling flexibility and computational efficiency. It is open source and object-oriented. As such, it can be customised and the range of models extended

    Imaging of Burkitt lymphoma in pediatric patients

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    The imaging procedures utilized at presentation in the diagnostic work-up of 19 children with Burkitt lymphoma were reviewed. The distribution of disease was compared to other tumors of childhood so that the most valuable modalities could be identified. Burkitt lymphoma is a rapidly growing tumor in the child, making it essential to suggest the diagnosis as quickly as possible so that biopsy and treatment can be instigated. The primary area of involvement was abdominal (15 of 19), gastrointestinal, intraperitoneal adenopathy, hepatic and pancreatic without retroperitoneal adenopathy. Pleural effusions were common without hilar and mediastinal adenopathy. This is in contrast to other tumors of childhood where mediastinal and hilar disease in the chest and retroperitoneal node involvement in the abdomen are common. Thus sonography is an excellent imaging modality, easily identifying the extent of the disease and so suggesting the diagnosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46683/1/247_2006_Article_BF02388718.pd

    Phenothiourea Sensitizes Zebrafish Cranial Neural Crest and Extraocular Muscle Development to Changes in Retinoic Acid and IGF Signaling

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    1-phenyl 2-thiourea (PTU) is a tyrosinase inhibitor commonly used to block pigmentation and aid visualization of zebrafish development. At the standard concentration of 0.003% (200 µM), PTU inhibits melanogenesis and reportedly has minimal other effects on zebrafish embryogenesis. We found that 0.003% PTU altered retinoic acid and insulin-like growth factor (IGF) regulation of neural crest and mesodermal components of craniofacial development. Reduction of retinoic acid synthesis by the pan-aldehyde dehydrogenase inhibitor diethylbenzaldehyde, only when combined with 0.003% PTU, resulted in extraocular muscle disorganization. PTU also decreased retinoic acid-induced teratogenic effects on pharyngeal arch and jaw cartilage despite morphologically normal appearing PTU-treated controls. Furthermore, 0.003% PTU in combination with inhibition of IGF signaling through either morpholino knockdown or pharmacologic inhibition of tyrosine kinase receptor phosphorylation, disrupted jaw development and extraocular muscle organization. PTU in and of itself inhibited neural crest development at higher concentrations (0.03%) and had the greatest inhibitory effect when added prior to 22 hours post fertilization (hpf). Addition of 0.003% PTU between 4 and 20 hpf decreased thyroxine (T4) in thyroid follicles in the nasopharynx of 96 hpf embryos. Treatment with exogenous triiodothyronine (T3) and T4 improved, but did not completely rescue, PTU-induced neural crest defects. Thus, PTU should be used with caution when studying zebrafish embryogenesis as it alters the threshold of different signaling pathways important during craniofacial development. The effects of PTU on neural crest development are partially caused by thyroid hormone signaling

    The alpha-kinase family: an exceptional branch on the protein kinase tree

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    The alpha-kinase family represents a class of atypical protein kinases that display little sequence similarity to conventional protein kinases. Early studies on myosin heavy chain kinases in Dictyostelium discoideum revealed their unusual propensity to phosphorylate serine and threonine residues in the context of an alpha-helix. Although recent studies show that some members of this family can also phosphorylate residues in non-helical regions, the name alpha-kinase has remained. During evolution, the alpha-kinase domains combined with many different functional subdomains such as von Willebrand factor-like motifs (vWKa) and even cation channels (TRPM6 and TRPM7). As a result, these kinases are implicated in a large variety of cellular processes such as protein translation, Mg2+ homeostasis, intracellular transport, cell migration, adhesion, and proliferation. Here, we review the current state of knowledge on different members of this kinase family and discuss the potential use of alpha-kinases as drug targets in diseases such as cancer

    Rethinking the study of human-wildlife coexistence

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    While coexistence with wildlife is a key goal of conservation efforts, little is known about it or how to study it. This essay briefly defines what we mean by coexistence, before considering issues arising from the conflict-oriented framing of human-wildlife interactions within conservation science. It proposes reasons for why conflict frameworks persist – and why much less work is done on coexistence. Methodological and fieldwork challenges for studying coexistence are outlined, with recommendations, based on the authors’ teaching experience and field experience in India and Africa. We recommend expanding the scope of our inquiries into the ways in which humans and wildlife already coexist beyond studies of rational behaviour, and the quantification of costs and benefits of wildlife to humans

    Fibroblast growth factor signalling controls nervous system patterning and pigment cell formation in Ciona intestinalis

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    During the development of the central nervous system (CNS), combinations of transcription factors and signalling molecules orchestrate patterning, specification and differentiation of neural cell types. In vertebrates, three types of melanin-containing pigment cells, exert a variety of functional roles including visual perception. Here we analysed the mechanisms underlying pigment cell specification within the CNS of a simple chordate, the ascidian Ciona intestinalis. Ciona tadpole larvae exhibit a basic chordate body plan characterized by a small number of neural cells. We employed lineage-specific transcription profiling to characterize the expression of genes downstream of fibroblast growth factor signalling, which govern pigment cell formation. We demonstrate that FGF signalling sequentially imposes a pigment cell identity at the expense of anterior neural fates. We identify FGF-dependent and pigment cell-specific factors, including the small GTPase, Rab32/38 and demonstrated its requirement for the pigmentation of larval sensory organs

    Historical Legacies in World Amphibian Diversity Revealed by the Turnover and Nestedness Components of Beta Diversity

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    Historic processes are expected to influence present diversity patterns in combination with contemporary environmental factors. We hypothesise that the joint use of beta diversity partitioning methods and a threshold-based approach may help reveal the effect of large-scale historic processes on present biodiversity. We partitioned intra-regional beta diversity into its turnover (differences in composition caused by species replacements) and nestedness-resultant (differences in species composition caused by species losses) components. We used piecewise regressions to show that, for amphibian beta diversity, two different world regions can be distinguished. Below parallel 37, beta diversity is dominated by turnover, while above parallel 37, beta diversity is dominated by nestedness. Notably, these regions are revealed when the piecewise regression method is applied to the relationship between latitude and the difference between the Last Glacial Maximum (LGM) and the present temperature but not when present energy-water factors are analysed. When this threshold effect of historic climatic change is partialled out, current energy-water variables become more relevant to the nestedness-resultant dissimilarity patterns, while mountainous areas are associated with higher spatial turnover. This result suggests that nested patterns are caused by species losses that are determined by physiological constraints, whereas turnover is associated with speciation and/or Pleistocene refugia. Thus, the new threshold-based view may help reveal the role of historic factors in shaping present amphibian beta diversity patterns
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