Chromosome Imbalance as a Driver of Sex Disparity in Disease

licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Published: 2014.04.01 It has long been recognized that men and women exhibit different risks for diverse disorders ranging from metabolic to autoimmune diseases. However, the underlying causes of these disparities remain obscure. Analysis of patients with chromosomal abnormalities, including Turner syndrome (45X) and Klinefelter syndrome (47XXY), has highlighted the importance of X-linked gene dosage as a contributing factor for disease susceptibility. Escape from X-inactivation and X-linked imprinting can result in transcriptional differences between normal men and women as well as in patients with sex chromosome abnormalities. Animal models support a role for X-linked gene dosage in disease with O-linked N-acetylglucosamine transferase (OGT) emerging as a prime candidate for a pleiotropic effector. OGT encodes a highly regulated nutrient-sensing epigenetic modifier with established links to immunity, metabolism and development

EpyNN: Educational python for Neural Networks

International audienceArtificial Neural Networks (ANNs) have achieved unequaled performance for numerous problems in many areas of Science, Business, Public Policy, and more. While experts are familiar with performanceoriented software and underlying theory, ANNs are difficult to comprehend for non-experts because it requires skills in programming, background in mathematics and knowledge of terminology and concepts. In this work, we release EpyNN, an educational Python resource meant for a public willing to understand key concepts and practical implementation of scalable ANN architectures from concise, homogeneous and idiomatic source code. EpyNN contains an educational Application Programming Interface (API), educational workflows from data preparation to ANN training and a documentation website setting side-by-side code, mathematics, graphical representation and text to facilitate learning and provide teaching material. Overall, EpyNN provides basics in Python for individuals who wish to learn, teach or develop from scratch

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X-inactivation normalizes O-GlcNAc transferase levels and generates an O-GlcNAc-depleted Barr bod

Insulin signaling controls the expression of O-GlcNAc transferase and its interaction with lipid microdomains

Lipid microdomains (rafts) are cholesterol-enriched dynamic ordered lipid domains belonging to cell membranes involved in diverse cellular functions, including signal transduction, membrane trafficking, and infection. Many studies have reported relationships between insulin signaling and lipid rafts. Likewise, links between insulin signaling and O-GlcNAcylation have also been described. However, the potential connection between O-GlcNAc and raft dynamics remains unexplored. Here we show that O-GlcNAc and the enzyme that creates this modification, O-GlcNAc transferase (OGT), are localized in rafts. On insulin stimulation, we observe time-dependent increases in OGT expression and localization within rafts. We show that these processes depend on activation of the phosphatidylinositol 3-kinase (PI3K) pathway. Inhibition of OGT does not significantly affect cholesterol synthesis and raft building but decreases insulin receptor expression and PI3K and mitogen-activated protein kinase pathway activation. Taken together, these findings indicate that O-GlcNAcylation, lipid rafts, and signaling pathways are spatiotemporally coordinated to enable fundamental cellular functions