New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Development and Commissioning of the Doppler-Shift Unit for the Measurement of the Ion Species Fractions and Beam Energy of the ESS Proton Source

International audienceESS proton source is in going to be soon delivered to the ESS project. In order to qualify the source, a series of beam instrumentation diagnostics have been designed and produced. In particular, a specific spectrograph dedicated to the fraction species measurement is currently commissioned. This instrument not only is capable of measuring the fraction species produced by the source, but also it can measure their energy and energy spread, the mass of the different species, and additional spectral rays coming from the gas species in presence in the vacuum chamber. We present in this paper the commissioning of this instrument, the Doppler Shift unit, dedicated to the measurement of the fraction species

Mutations and variants of ONECUT1 in diabetes

Genes involved in distinct diabetes types suggest shared disease mechanisms. Here we show that One Cut Homeobox 1 (ONECUT1) mutations cause monogenic recessive syndromic diabetes in two unrelated patients, characterized by intrauterine growth retardation, pancreas hypoplasia and gallbladder agenesis/hypoplasia, and early-onset diabetes in heterozygous relatives. Heterozygous carriers of rare coding variants of ONECUT1 define a distinctive subgroup of diabetic patients with early-onset, nonautoimmune diabetes, who respond well to diabetes treatment. In addition, common regulatory ONECUT1 variants are associated with multifactorial type 2 diabetes. Directed differentiation of human pluripotent stem cells revealed that loss of ONECUT1 impairs pancreatic progenitor formation and a subsequent endocrine program. Loss of ONECUT1 altered transcription factor binding and enhancer activity and NKX2.2/NKX6.1 expression in pancreatic progenitor cells. Collectively, we demonstrate that ONECUT1 controls a transcriptional and epigenetic machinery regulating endocrine development, involved in a spectrum of diabetes, encompassing monogenic (recessive and dominant) as well as multifactorial inheritance. Our findings highlight the broad contribution of ONECUT1 in diabetes pathogenesis, marking an important step toward precision diabetes medicine

Effervescence in champagne and sparkling wines: From bubble bursting to droplet evaporation

International audienceWhen a bubble reaches an air-liquid interface, it ruptures, projecting a multitude of tiny droplets in the air. Across the oceans, an estimated 1018 to 1020 bubbles burst every second, and form the so called sea spray, a major player in earth's climate system. At a smaller scale, in a glass of champagne about a million bubbles nucleate on the wall, rise towards the surface and burst, giving birth to a particular aerosol that holds a concentrate of wine aromas. Based on the model experiment of a single bubble bursting in simple liquids, we depict each step of this effervescence, from bubble bursting to drop evaporation. In particular, we propose simple scaling laws for the jet velocity and the top drop size. We unravel experimentally the intricate roles of bubble shape, capillary waves, gravity, and liquid properties in the jet dynamics and the drop detachment. We demonstrate how damping action of viscosity produces faster and smaller droplets and more generally how liquid properties enable to control the bubble bursting aerosol characteristics. In this context, the particular case of Champagne wine aerosol is studied in details and the key features of this aerosol are identified. We demonstrate that compared to a still wine, champagne fizz drastically enhances the transfer of liquid into the atmosphere. Conditions on bubble radius and wine viscosity that optimize aerosol evaporation are provided. These results pave the way towards the fine tuning of aerosol characteristics and flavor release during sparkling wine tasting, a major issue of the sparkling wine industry