An ACACB Variant Implicated in Diabetic Nephropathy Associates with Body Mass Index and Gene Expression in Obese Subjects

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Comparing United States and Canadian population exposures from National Biomonitoring Surveys: Bisphenol A intake as a case study

The Centers for Disease Control and Prevention provides biomonitoring data in the United States as part of the National Health and Nutrition Examination Survey (NHANES). Recently, Statistics Canada initiated a similar survey — the Canadian Health Measures Survey (CHMS). Comparison of US and Canadian biomonitoring data can generate hypotheses regarding human exposures from environmental media and consumer products. To ensure that such comparisons are scientifically meaningful, it is essential to first evaluate aspects of the surveys' methods that can impact comparability of data. We examined CHMS and NHANES methodologies, using bisphenol A (BPA) as a case study, to evaluate whether survey differences exist that would hinder our ability to compare chemical concentrations between countries. We explored methods associated with participant selection, urine sampling, and analytical methods. BPA intakes were also estimated to address body weight differences between countries. Differences in survey methods were identified but are unlikely to have substantial impacts on inter-survey comparisons of BPA intakes. BPA intakes for both countries are below health-based guidance values set by the US, Canada and the European Food Safety Authority. We recommend that before comparing biomonitoring data between surveys, a thorough review of methodologic aspects that might impact biomonitoring results be conducted

Coordinately Regulated Alternative Splicing of Genes Involved in Cholesterol Biosynthesis and Uptake

Genes involved in cholesterol biosynthesis and uptake are transcriptionally regulated in response to cellular sterol content in a coordinated manner. A number of these genes, including 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and LDL receptor (LDLR), undergo alternative splicing, resulting in reductions of enzyme or protein activity. Here we demonstrate that cellular sterol depletion suppresses, and sterol loading induces, alternative splicing of multiple genes involved in the maintenance of cholesterol homeostasis including HMGCR and LDLR, the key regulators of cellular cholesterol biosynthesis and uptake, respectively. These changes were observed in both in vitro studies of the HepG2 human hepatoma derived cell line, as well as in vivo studies of St. Kitts vervets, also known as African green monkeys, a commonly used primate model for investigating cholesterol metabolism. These effects are mediated in part by sterol regulation of polypyrimidine tract binding protein 1 (PTBP1), since knock-down of PTBP1 eliminates sterol induced changes in alternative splicing of several of these genes. Single nucleotide polymorphisms (SNPs) that influence HMGCR and LDLR alternative splicing (rs3846662 and rs688, respectively), have been associated with variation in plasma LDL-cholesterol levels. Sterol-induced changes in alternative splicing are blunted in carriers of the minor alleles for each of these SNPs, indicating an interaction between genetic and non-genetic regulation of this process. Our results implicate alternative splicing as a novel mechanism of enhancing the robust transcriptional response to conditions of cellular cholesterol depletion or accumulation. Thus coordinated regulation of alternative splicing may contribute to cellular cholesterol homeostasis as well as plasma LDL levels

Pervasive transition of the Brazilian land-use system

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Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field