Sex differences in gene expression in the human fetal brain, bioRxiv, 2018-11-30

ABSTRACTWidespread structural, chemical and molecular differences have been reported between the male and female human brain. Although several neurodevelopmental disorders are more commonly diagnosed in males, little is known regarding sex differences in early human brain development. Here, we used RNA sequencing data from a large collection of human brain samples from the second trimester of gestation (N = 120) to assess sex biases in gene expression within the human fetal brain. In addition to 43 genes (102 Ensembl transcripts) transcribed from the Y-chromosome in males, we detected sex differences in the expression of 2558 autosomal genes (2723 Ensembl transcripts) and 155 genes on the X-chromosome (207 Ensembl transcripts) at a false discovery rate (FDR) &lt; 0.1. Genes exhibiting sex-biased expression in human fetal brain are enriched for high-confidence risk genes for autism and other developmental disorders. Male-biased genes are enriched for expression in neural progenitor cells, whereas female-biased genes are enriched for expression in Cajal-Retzius cells and glia. All gene- and transcript-level data are provided as an online resource (available at <jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=uri xlinkhref=httpfgen.psycm.cf.ac.ukFBSeq1>httpfgen.psycm.cf.ac.ukFBSeq1<jatsext-link>) through which researchers can search, download and visualize data pertaining to sex biases in gene expression during early human brain development.

biorxiv genomics 200-500-users 2018

Long-Term Effects of a Novel Continuous Remote Care Intervention Including Nutritional Ketosis for the Management of Type 2 Diabetes A 2-year Non-randomized Clinical Trial, bioRxiv, 2018-11-28

ABSTRACTOBJECTIVEStudies on long-term sustainability of low-carbohydrate approaches to treat diabetes are limited. We aim to assess the effects of a continuous care intervention (CCI) on retention, glycemic control, weight, body composition, cardiovascular, liver, kidney, thyroid, inflammatory markers, diabetes medication usage and disease outcomes at 2 years in adults with type 2 diabetes (T2D).RESEARCH DESIGN AND METHODSAn open label, non-randomized, controlled study with 262 and 87 participants with T2D were enrolled in the CCI and usual care (UC) groups, respectively.RESULTSSignificant changes from baseline to 2 years in the CCI group included HbA1c (−12% from 7.7±0.1%); fasting glucose (−18% from 163.67±3.90 mgdL); fasting insulin (−42% from 27.73±1.26 pmol L-1); weight (−10% from 114.56±0.60 kg); systolic blood pressure (−4% from 131.7±0.9 mmHg); diastolic blood pressure (−4% from 81.8±0.5 mmHg); triglycerides (−22% from 197.2±9.1 mgdL); HDL-C (+19% from 41.8±0.9 mgdL), and liver alanine transaminase (−21% from 29.16±0.97 UL). Spine bone mineral density in the CCI group was unchanged. Glycemic control medication use (excluding metformin) among CCI participants declined (from 56.9% to 26.8%, P=1.3×10-11) including prescribed insulin (−62%) and sulfonylureas (−100%). The UC group had no significant changes in these parameters (except uric acid and anion gap) or diabetes medication use. There was also significant resolution of diabetes (reversal, 53.5%; remission, 17.6%) in the CCI group but not in UC. All the reported improvements had p-values &lt;0.00012.CONCLUSIONSThe CCI sustained long-term beneficial effects on multiple clinical markers of diabetes and cardiometabolic health at 2 years while utilizing less medication. The intervention was also effective in the resolution of diabetes and visceral obesity, with no adverse effect on bone health.TRIAL REGISTRATIONClinicaltrials.gov <jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=clintrialgov xlinkhref=NCT02519309>NCT02519309<jatsext-link>

biorxiv clinical-trials 200-500-users 2018

 

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