Genetic Susceptibility Determines β-Cell Function and Fasting Glycemia Trajectories Throughout Childhood: A 12-Year Cohort Study (EarlyBird 76)

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The genome and population genomics of allopolyploid Coffea arabica reveal the diversification history of modern coffee cultivars.

Coffea arabica, an allotetraploid hybrid of Coffea eugenioides and Coffea canephora, is the source of approximately 60% of coffee products worldwide, and its cultivated accessions have undergone several population bottlenecks. We present chromosome-level assemblies of a di-haploid C. arabica accession and modern representatives of its diploid progenitors, C. eugenioides and C. canephora. The three species exhibit largely conserved genome structures between diploid parents and descendant subgenomes, with no obvious global subgenome dominance. We find evidence for a founding polyploidy event 350,000–610,000 years ago, followed by several pre-domestication bottlenecks, resulting in narrow genetic variation. A split between wild accessions and cultivar progenitors occurred ~30.5 thousand years ago, followed by a period of migration between the two populations. Analysis of modern varieties, including lines historically introgressed with C. canephora, highlights their breeding histories and loci that may contribute to pathogen resistance, laying the groundwork for future genomics-based breeding of C. arabica

Tuning Strain Localization in Polycrystalline Nickel-Based Superalloys by Thermomechanical Processing

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Development of overgrown grains during sub-solvus heat treatment in a polycrystalline γ-γ’ Nickel-based superalloy

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The Role of Target Melting in Particle Impact Ignition with Inert Particulate

The high gas temperatures and oxygen pressures in the turbine of oxygen-rich turbomachinery put conventional engineering alloys such as IN718 at risk of particle impact ignition, i.e., metal fires initiated when particulate strikes a solid surface. The standard model of particle impact ignition assumes that the impacting particle must first ignite in order to kindle to the target material. Here, we invalidate this belief through particle impact ignition experiments which show that IN718 can ignite when struck by inert Al2O3 particles with supersonic impact velocities. Through post-mortem analysis of non-ignited samples, we find that subsonic particle impact causes minimal crater damage whereas supersonic particle impact leaves extensive crater plasticity and pileup, with evidence of molten ejecta near the impact site. Complementary finite element simulations of supersonic impact events confirm extreme adiabatic heating and localized melting. These findings demonstrate that particle impact can drive target ignition even in the absence of particle burning provided the thermal excursion at impact exceeds the melting point of the target material

Systematic analysis of differential rhythmic liver gene expression mediated by the circadian clock and feeding rhythms

The circadian clock and feeding rhythms are both important regulators of rhythmic gene expression in the liver. To further dissect the respective contributions of feeding and the clock, we analyzed differential rhythmicity of liver tissue samples across several conditions. We developed a statistical method tailored to compare rhythmic liver messenger RNA (mRNA) expression in mouse knockout models of multiple clock genes, as well as PARbZip output transcription factors (Hlf/Dbp/Tef). Mice were exposed to ad libitum or night-restricted feeding under regular light-dark cycles. During ad libitum feeding, genetic ablation of the core clock attenuated rhythmic-feeding patterns, which could be restored by the night-restricted feeding regimen. High-amplitude mRNA expression rhythms in wild-type livers were driven by the circadian clock, but rhythmic feeding also contributed to rhythmic gene expression, albeit with significantly lower amplitudes. We observed that Bmal1 and Cry1/2 knockouts differed in their residual rhythmic gene expression. Differences in mean expression levels between wild types and knockouts correlated with rhythmic gene expression in wild type. Surprisingly, in PARbZip knockout mice, the mean expression levels of PARbZip targets were more strongly impacted than their rhythms, potentially due to the rhythmic activity of the D-box-repressor NFIL3. Genes that lost rhythmicity in PARbZip knockouts were identified to be indirect targets. Our findings provide insights into the diurnal transcriptome in mouse liver as we identified the differential contributions of several core clock regulators. In addition, we gained more insights on the specific effects of the feeding-fasting cycle

Adipose tissue angiogenesis genes are down-regulated by grape polyphenols supplementation during a human overfeeding trial

International audienceThe adaptive response to overfeeding is associated with profound modifications of gene expression in adipose tissue to support lipid storage and weight gain. The objective of this study was to assess in healthy lean men whether a supplementation with polyphenols could interact with these molecular adaptations. Abdominal subcutaneous adipose tissue biopsies were sampled from 42 subjects participating to an overfeeding protocol providing an excess of 50% of their total energy expenditure for 31 days, and who were supplemented with 2 g/day of grape polyphenols or a placebo. Gene expression profiling was performed by RNA sequencing. Overfeeding led to a modification of the expression of 163 and 352 genes in the placebo and polyphenol groups, respectively. The GO functions of these genes were mostly involved in lipid metabolism, followed by genes involved in adipose tissue remodeling and expansion. In response to overfeeding, 812 genes were differentially regulated between groups. Among them, a set of 41 genes were related to angiogenesis and were down-regulated in the polyphenol group. Immunohistochemistry targeting PECAM1, as endothelial cell marker, confirmed reduced angiogenesis in this group. Finally, quercetin and isorhamnetin, two polyphenol species enriched in the plasma of the volunteers submitted to the polyphenols, were found to inhibit human umbilical vein endothelial cells migration in vitro. Polyphenol supplementation do not prevent the regulation of genes related to lipid metabolism in human adipose tissue during overfeeding, but impact the angiogenesis pathways. This may potentially contribute to a protection against adipose tissue expansion during dynamic phase of weight gain

Insights into Plastic Localization by Crystallographic Slip from Emerging Experimental and Numerical Approaches

International audienceAdvanced experimental and numerical approaches are being developed to capture the localization of plasticity at the nanometer scale as a function of the multiscale and heterogeneous microstructure present in metallic materials. These innovative approaches promise new avenues to understand microstructural effects on mechanical properties, accelerate alloy design, and enable more accurate mechanical property prediction. This article provides an overview of emerging approaches with a focus on the localization of plasticity by crystallographic slip. New insights into the mechanisms and mechanics of strain localization are addressed. The consequences of the localization of plasticity by deformation slip for mechanical properties of metallic materials are also detaile

Disruption of the circadian clock component BMAL1 elicits an endocrine adaption impacting on insulin sensitivity and liver disease.

SignificanceWhile increasing evidence associates the disruption of circadian rhythms with pathologic conditions, including obesity, type 2 diabetes, and nonalcoholic fatty liver diseases (NAFLD), the involved mechanisms are still poorly described. Here, we show that, in both humans and mice, the pathogenesis of NAFLD is associated with the disruption of the circadian clock combined with perturbations of the growth hormone and sex hormone pathways. However, while this condition protects mice from the development of fibrosis and insulin resistance, it correlates with increased fibrosis in humans. This suggests that the perturbation of the circadian clock and its associated disruption of the growth hormone and sex hormone pathways are critical for the pathogenesis of metabolic and liver diseases