Induction and inhibition of Drosophila X chromosome gene expression are both impeded by the dosage compensation complex

Sex chromosomes frequently differ from the autosomes in the frequencies of genes with sexually dimorphic or tissue-specific expression. Multiple hypotheses have been put forth to explain the unique gene content of the X chromosome, including selection against male-beneficial X-linked alleles, expression limits imposed by the haploid dosage of the X in males, and interference by the dosage compensation complex on expression in males. Here, we investigate these hypotheses by examining differential gene expression in Drosophila melanogaster following several treatments that have widespread transcriptomic effects: bacterial infection, viral infection, and abiotic stress. We found that genes that are induced (upregulated) by these biotic and abiotic treatments are frequently under-represented on the X chromosome, but so are those that are repressed (downregulated) following treatment. We further show that whether a gene is bound by the dosage compensation complex in males can largely explain the paucity of both up- and downregulated genes on the X chromosome. Specifically, genes that are bound by the dosage compensation complex, or close to a dosage compensation complex high-affinity site, are unlikely to be up- or downregulated after treatment. This relationship, however, could partially be explained by a correlation between differential expression and breadth of expression across tissues. Nonetheless, our results suggest that dosage compensation complex binding, or the associated chromatin modifications, inhibit both up- and downregulation of X chromosome gene expression within specific contexts, including tissue-specific expression. We propose multiple possible mechanisms of action for the effect, including a role of Males absent on the first, a component of the dosage compensation complex, as a dampener of gene expression variance in both males and females. This effect could explain why the Drosophila X chromosome is depauperate in genes with tissue-specific or induced expression, while the mammalian X has an excess of genes with tissue-specific expression

The impact of obesity on different glucose tolerance status with incident cardiovascular disease and mortality events over 15 years of follow-up: a pooled cohort analysis

Abstract Background The effect of obesity in different glucose tolerance statuses i.e. normoglycemia (NGT), pre-diabetes, and type 2 diabetes (T2DM) on cardiovascular disease (CVD) and mortality has been an area of ongoing debate and uncertainty. In the present study, we aimed to examine the impact of being obese, whether general or central separately, in comparison with non-obese in different glucose tolerance statuses on the above outcomes. Methods The study population included 18,184 participants aged 30–60 years (9927 women) from three longitudinal studies, including Atherosclerosis Risk in Communities, Multi-Ethnic Study of Atherosclerosis, and Tehran Lipid and Glucose Study. Glucose tolerance status was defined as NGT (fasting plasma glucose < 5.55 mmol/L), pre-diabetes (5.55–7.00 mmol/L), and T2DM (≥ 7 mmol/L or taking any medication for diabetes). Moreover, general and central obesity were defined based on body mass index and waist circumference (WC), respectively. Multivariable stratified Cox regression analysis was used to estimate hazard ratios (HRs (95% CI)) for CVD and mortality events. Results During a 16-year follow-up, 2733 CVD events, 1101 CV mortality, and 3678 all-cause mortality events were recorded. We observed that being generally obese in comparison with non-obese increased the risk of CV and all-cause mortality in all glucose tolerance statuses; while considering CVD events, only among individuals with T2DM, the presence of general obesity was associated with marginally significant higher risk [1.19 (0.98–1.43); p-value = 0.07]. Regarding central adiposity, multivariate analysis revealed that elevated WC in NGT participants is associated with incident CVD [1.27(1.12–1.46)] and all-cause mortality [1.13(1.00–1.28)]. Moreover, central adiposity increased the risk of CV mortality in pre-diabetes individuals [1.47 (1.11–1.95)]. Conclusion Findings from this pooled prospective cohort studies provide evidence that general obesity shows an unfavorable association with CV and all-cause mortality among the general population irrespective of their glucose tolerance statusThe findings imply that it's important to take into account the requirement and magnitude of weight reduction in people who are obese when offering guidance

Additional file 1 of The impact of obesity on different glucose tolerance status with incident cardiovascular disease and mortality events over 15 years of follow-up: a pooled cohort analysis

Additional file 1: Table S1. Baseline characteristics of subjects, stratified by study and gender. Fig S1. Study Flowchart CV Cardiovascular, ARIC Atherosclerosis Risk in Communities, MESA Multi-Ethnic Study of Atherosclerosis, TLGS Tehran Lipid and Glucose Study. Fig S2. The annual incidence rates of cardiovascular disease (CVD) by diabesity phenotypes in men and women, separately. Normoglycemia: FPG<100 mg/dl & no medication; pre-diabetes: FPG 100-126 mg/dl and no medication; type 2 diabetes; FPG ≥126 mg/dl or using medication. Obesity (BMI≥30 kg/m2). Fig S3. The annual incidence rates of cardiovascular (CV) mortality by diabesity phenotypes in men and women, separately. Normoglycemia: FPG<100 mg/dl & no medication; pre-diabetes: FPG 100-126 mg/dl and no medication; type 2 diabetes; FPG ≥126 mg/dl or using medication. Obesity (BMI≥30 kg/m2). Fig S4. The annual incidence rates of all-cause mortality by diabesity phenotypes in men and women, separately. Normoglycemia: FPG<100 mg/dl & no medication; pre-diabetes: FPG 100-126 mg/dl and no medication; type 2 diabetes; FPG ≥126 mg/dl or using medication. General obesity (BMI≥30 kg/m2)

Complement-Mediated Regulation of Metabolism and Basic Cellular Processes

Complement is well appreciated as critical arm of innate immunity. It is required for the removal of invading pathogens and functions by direct pathogen destruction and through the activation of innate and adaptive immune cells. However, complement activation and function is not confined to the extracellular space but also occurs within cells. Recent work indicates that complement activation regulates key metabolic pathways and thus can impact fundamental processes of the cell, such as survival, proliferation, and autophagy. Novel identified functions of complement include a key role in shaping metabolic reprogramming, which underlies T cell effector differentiation, and a role as a nexus for interactions with other effector systems, in particular the inflammasome and Notch transcription factor networks. This review focuses on the contributions of complement to basic processes of the cell, in particular the integration of complement with cellular metabolism, and the potential implications in infection and other disease settings