993 resultados para Discovery Tools


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The aim of this study was to evaluate and improve the accuracy of plant uptake models for neutral hydrophobic organic pollutants (1 < logKOW < 9, −8 < logKAW < 0) used in regulatory exposure assessment tools, using uncertainty and sensitivity analyses. The models considered were RAIDAR, EUSES, CSOIL, CLEA, and CalTOX. In this research, CSOIL demonstrated the best performance of all five exposure assessment tools for root uptake from polluted soil in comparison with observed data, but no model predicted shoot uptake well. Recalibration of the transpiration and volatilisation parameters improved the performance of CSOIL and CLEA. The dominant pathway for shoot uptake simulated differed according to the properties of the chemical under consideration; those with a higher air–water partition coefficient were transported into shoots via the soil-air-plant pathway, while chemicals with a lower octanol–water partition coefficient and air–water partition coefficient were transported via the root. The soil organic carbon content was a particularly sensitive parameter in each model and using a site specific value improved model performance.

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There is a critical need for screening and diagnostic tools (SDT) for autism spectrum conditions (ASC) in regional languages in South Asia. To address this, we translated four widely used SDT (Social Communication Disorder Checklist, Autism Spectrum Quotient, Social Communication Questionnaire, and Autism Diagnostic Observation Schedule) into Bengali and Hindi, two main regional languages (∼ 360 million speakers), and tested their usability in children with and without ASC. We found a significant difference in scores between children with ASC (n = 45 in Bengali, n = 40 in Hindi) and typically developing children (n = 43 in Bengali, n = 42 in Hindi) on all SDTs. These results demonstrate that these SDTs are usable in South Asia, and constitute an important resource for epidemiology research and clinical diagnosis in the region.

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Myostatin plays a fundamental role in regulating the size of skeletal muscles. To date, only a single myostatin gene and no splice variants have been identified in mammals. Here we describe the splicing of a cryptic intron that removes the coding sequence for the receptor binding moiety of sheep myostatin. The deduced polypeptide sequence of the myostatin splice variant (MSV) contains a 256 amino acid N-terminal domain, which is common to myostatin, and a unique C-terminus of 65 amino acids. Western immunoblotting demonstrated that MSV mRNA is translated into protein, which is present in skeletal muscles. To determine the biological role of MSV, we developed an MSV over-expressing C2C12 myoblast line and showed that it proliferated faster than that of the control line in association with an increased abundance of the CDK2/Cyclin E complex in the nucleus. Recombinant protein made for the novel C-terminus of MSV also stimulated myoblast proliferation and bound to myostatin with high affinity as determined by surface plasmon resonance assay. Therefore, we postulated that MSV functions as a binding protein and antagonist of myostatin. Consistent with our postulate, myostatin protein was co-immunoprecipitated from skeletal muscle extracts with an MSV-specific antibody. MSV over-expression in C2C12 myoblasts blocked myostatin-induced Smad2/3-dependent signaling, thereby confirming that MSV antagonizes the canonical myostatin pathway. Furthermore, MSV over expression increased the abundance of MyoD, Myogenin and MRF4 proteins (P,0.05), which indicates that MSV stimulates myogenesis through the induction of myogenic regulatory factors. To help elucidate a possible role in vivo, we observed that MSV protein was more abundant during early post-natal muscle development, while myostatin remained unchanged, which suggests that MSV may promote the growth of skeletal muscles. We conclude that MSV represents a unique example of intra-genic regulation in which a splice variant directly antagonizes the biological activity of the canonical gene product.