A sex-specific switch between visual and olfactory inputs underlies adaptive sex differences in behavior

While males and females largely share the same genome and nervous system, they differ profoundly in reproductive investments and require distinct behavioral, morphological and physiological adaptations. How can the nervous system, while bound by both developmental and biophysical constraints, produce these sexdifferences in behavior? Here we uncover a novel dimorphism in Drosophila melanogaster that allows deployment of completely different behavioral repertoires in males and females with minimum changes to circuit architecture. Sexual differentiation of only a small number of higher-order neurons in the brain leads to a change in connectivity related to the primary reproductive needs of both sexes - courtship pursuit in males and communal oviposition in females. This study explains how an apparently similar brain generates distinct behavioral repertoires in the two sexes and presents a fundamental principle of neural circuit organization that may be extended to other species

Effects of sedentary behaviour interventions on biomarkers of cardiometabolic risk in adults: systematic review with meta-analyses.

CONTEXT/PURPOSE: Observational and acute laboratory intervention research has shown that excessive sedentary time is associated adversely with cardiometabolic biomarkers. This systematic review with meta-analyses synthesises results from free living interventions targeting reductions in sedentary behaviour alone or combined with increases in physical activity. METHODS: Six electronic databases were searched up to August 2019 for sedentary behaviour interventions in adults lasting for ≥7 days publishing cardiometabolic biomarker outcomes covering body anthropometry, blood pressure, glucose and lipid metabolism, and inflammation (54 studies). The pooled effectiveness of intervention net of control on 15 biomarker outcomes was evaluated using random effects meta-analyses in the studies with control groups not providing other relevant interventions (33 studies; 6-25 interventions analysed). RESULTS: Interventions between 2 weeks and 0.05) were also small, and beneficial in direction except for fat-free mass (≈ 0.0 kg). Heterogeneity ranged widely (I2=0.0-72.9). CONCLUSIONS: Our review of interventions targeting sedentary behaviour reductions alone, or combined with increases in physical activity, found evidence of effectiveness for improving some cardiometabolic risk biomarkers to a small degree. There was insufficient evidence to evaluate inflammation or vascular function. Key limitations to the underlying evidence base include a paucity of high-quality studies, interventions lasting for ≥12 months, sensitive biomarkers and clinical study populations (eg, type 2 diabetes). PROSPERO TRIAL REGISTRATION NUMBER: CRD42016041742.PD is supported by a National Health and Medical Research Council (NHMRC) of Australia Fellowship (#1142685) and the UK Medical Research Council [#MC_UU_12015/3]. NO, DD, GH are supported by NHMRC of Australia Fellowships (#1003960, #1078360 & #1086029). The funders had no role in the data analysis or interpretation of the results

Low-level repressive histone marks fine-tune gene transcription in neural stem cells

Coordinated regulation of gene activity by transcriptional and translational mechanisms poise stem cells for a timely cell-state transition during differentiation. Although important for all stemness-to-differentiation transitions, mechanistic understanding of the fine-tuning of gene transcription is lacking due to the compensatory effect of translational control. We used intermediate neural progenitor (INP) identity commitment to define the mechanisms that fine-tune stemness gene transcription in fly neural stem cells (neuroblasts). We demonstrate that the transcription factor FruitlessC (FruC) binds cis-regulatory elements of most genes uniquely transcribed in neuroblasts. Loss of fruC function alone has no effect on INP commitment but drives INP dedifferentiation when translational control is reduced. FruC negatively regulates gene expression by promoting low-level enrichment of the repressive histone mark H3K27me3 in gene cis-regulatory regions. Identical to fruC loss-of-function, reducing Polycomb Repressive Complex 2 activity increases stemness gene activity. We propose low-level H3K27me3 enrichment fine-tunes gene transcription in stem cells, a mechanism likely conserved from flies to humans

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations

Does the type of activity break from prolonged sitting differentially impact on postprandial blood glucose reductions? An exploratory analysis

Frequent breaks in prolonged sitting are associated beneficially with glycaemic control. However, the contribution of energy expenditure to this relationship has not been well characterised. In this exploratory analysis, data from 3 laboratory trials that standardised test meals, cohort characteristics (overweight/obese, sedentary), and break frequency and duration were pooled. Higher energy expenditures of different types of breaks (standing, light- or moderate-intensity walking) were associated with lower postprandial glucose and insulin responses in a dose-dependent manner

Regular brief interruptions to sitting after a high-energy evening meal attenuate glycemic excursions in overweight/obese adults

Background and aims: Modern Western lifestyles are characterized by consumption of approximately 45% of total daily energy intake at the evening meal, followed by prolonged sitting while watching television (TV), which may deleteriously impact glycemic control. After a high-energy evening meal (dinner), we examined whether regular, brief activity bouts during TV commercial breaks could acutely lower postprandial glucose and insulin responses in overweight/obese adults, compared to prolonged uninterrupted sitting. Methods and results: Nine overweight/obese adults (29.7 ± 4.06 kg m−2; aged 32 ± 3 years; 5 male) completed two laboratory-based conditions of three and a half hours: prolonged sitting during TV viewing (SIT); and, prolonged sitting interrupted every 20 min with 3 min of light-intensity body-weight resistance activities (active commercial breaks; ACBs). Venous postprandial glucose and insulin responses to dinner were calculated as positive incremental area under the curve (iAUC) from baseline. Interstitial glucose was measured using a continuous glucose monitor and quantified as total AUC (tAUC). Compared to SIT, plasma glucose iAUC was reduced by 33% [3.4 ± 1.0 vs 5.1 ± 1.0 (mean ± SEM) mmol h·L−1, p = 0.019] and plasma insulin iAUC by 41% (813 ± 224 vs 1373 ± 224, p = 0.033 pmol h·L−1) for the ACB condition. During the ACB condition there was a significant reduction in interstitial glucose tAUC (24.4 ± 5.2 vs 26.9 ± 5.2 mmol h·L−1, p < 0.001), but this did not persist beyond the laboratory observation period. Conclusions: Regular brief light-intensity activity bouts can attenuate glycemic responses during television viewing time following a high-energy evening meal in overweight/obese adults

Effects of sedentary behaviour interventions on biomarkers of cardiometabolic risk in adults: systematic review with meta-analyses

Context/purpose: Observational and acute laboratory intervention research has shown that excessive sedentary time is associated adversely with cardiometabolic biomarkers. This systematic review with meta-analyses synthesises results from free living interventions targeting reductions in sedentary behaviour alone or combined with increases in physical activity. Methods: Six electronic databases were searched up to August 2019 for sedentary behaviour interventions in adults lasting for ≥7 days publishing cardiometabolic biomarker outcomes covering body anthropometry, blood pressure, glucose and lipid metabolism, and inflammation (54 studies). The pooled effectiveness of intervention net of control on 15 biomarker outcomes was evaluated using random effects meta-analyses in the studies with control groups not providing other relevant interventions (33 studies; 6-25 interventions analysed). Results: Interventions between 2 weeks an

Interrupting Sitting Time with Simple Resistance Activities Lowers Postprandial Insulinemia in Adults with Overweight or Obesity.

OBJECTIVE: This study aimed to examine the effects on postprandial glucose and insulin responses of interrupting sitting time with brief bouts of simple resistance activities (SRAs) in adults with overweight or obesity. METHODS: Participants (n = 19) were recruited for a randomized crossover trial involving the following two 6-hour conditions: (1) uninterrupted sitting or (2) sitting with 3-minute bouts of SRAs (half-squats, calf raises, gluteal contractions, and knee raises) every 30 minutes (total duration = 27 minutes). Incremental areas under the curve (iAUC) for glucose, insulin, and insulin:glucose ratio were analyzed as prespecified secondary outcomes using mixed-effects log-linear regression adjusted for sex, BMI, treatment order, and preprandial values. Results are reported as multiplicative change (exponentiated coefficient [EC] with 95% CI) relative to the control condition. RESULTS: Glucose iAUC during the SRA condition was not significantly different from the prolonged sitting condition (EC = 0.92; 95% CI: 0.73-1.16; P = 0.43). However, SRAs lowered the postprandial insulin response by 26% (EC = 0.74; 95% CI: 0.64-0.85; P < 0.001), and there was a 23% lowering of the iAUC for insulin:glucose (EC = 0.77; 95% CI: 0.67-0.89; P < 0.001). CONCLUSIONS: In adults with overweight or obesity, frequent interruptions to sitting time with SRAs lowered postprandial insulin responses and insulin:glucose. These findings may have implications for mitigating cardiometabolic risk in adults with overweight or obesity who engage in prolonged periods of sitting.This work was supported by a National Health and Medical Research Council Centre of Research Excellence grant (grant number NHMRC #APP1057608). PCD, BAK, NO, DJG, DWD were supported by NHMRC Research Fellowship Scheme (1142685, 1059454, 1118225, 1080914, and 1078360, respectively). This work was also supported in part by the Victorian Government’s Operational Infrastructure Support Program