Deleon Adler (servercheque3)
Meanwhile, there was remarkably little change in food supply in countries in the sub-Saharan Africa region. These changes have led to a partial global convergence in national supply of animal source foods and sugar, and a divergence in vegetables, and seafood and oilcrops. Our analysis has generated a novel characterisation of food supply that highlights the interdependence of multiple food types in national food systems. A better understanding of how these patterns have evolved and will continue to change is needed to support the delivery of healthy and sustainable food system policies.Background Necrotic foci with surrounding hypoxic cellular pseudopalisades and microvascular hyperplasia are histological features found in glioblastoma (GBM). We have previously shown that monocarboxylate transporter 4 (MCT4) is highly expressed in necrotic/hypoxic regions in GBM and that increased levels of MCT4 are associated with worse clinical outcomes. Methods A combined transcriptomics and metabolomics analysis was performed to study the effects of MCT4 depletion in hypoxic GBM neurospheres. Stable and inducible MCT4-depletion systems were used to evaluate the effects of and underlining mechanisms associated with MCT4 depletion in vitro and in vivo, alone and in combination with radiation. Results This study establishes that conditional depletion of MCT4 profoundly impairs self-renewal and reduces the frequency and tumorigenicity of aggressive, therapy-resistant, glioblastoma stem cells. Mechanistically, we observed that MCT4 depletion induces anaplerotic glutaminolysis and abrogates de novo pyrimidine biosynthesis. The latter results in a dramatic increase in DNA damage and apoptotic cell death, phenotypes that were readily rescued by pyrimidine nucleosides supplementation. Consequently, we found that MCT4 depletion promoted a significant prolongation of survival of animals bearing established orthotopic xenografts, an effect that was extended by adjuvant treatment with focused radiation. Conclusions Our findings establish a novel role for MCT4 as a critical regulator of cellular deoxyribonucleotide levels and provide a new therapeutic direction related to MCT4 depletion in GBM. © The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.Genome-wide association study (GWAS) has been the driving force for identifying association between genetic variants and human phenotypes. Thousands of GWAS summary statistics covering a broad range of human traits and diseases are now publicly available. These GWAS have proven their utility for a range of secondary analyses, including in particular the joint analysis of multiple phenotypes to identify new associated genetic variants. However, although several methods have been proposed, there are very few large-scale applications published so far because of challenges in implementing these methods on real data. Here, we present JASS (Joint Analysis of Summary Statistics), a polyvalent Python package that addresses this need. Our package incorporates recently developed joint tests such as the omnibus approach and various weighted sum of Z-score tests while solving all practical and computational barriers for large-scale multivariate analysis of GWAS summary statistics. This includes data cleaning and harmonization tools, an efficient algorithm for fast derivation of joint statistics, an optimized data management process and a web interface for exploration purposes. Both benchmark analyses and real data applications demonstrated the robustness and strong potential of JASS for the detection of new associated genetic variants. Our package is freely available at https//gitlab.pasteur.fr/statistical-genetics/jass. © The Author(s) 2019. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.Background Mesenchymal stromal cells (MSCs) are widely used in clinical trials for bone repair and regeneration. De
