Knockdown of Indy/CeNac2 extends Caenorhabditis elegans life span by inducing AMPK/aak-2

Reducing the expression of the Indy (Acronym for 'I'm Not Dead, Yet') gene in lower organisms promotes longevity and leads to a phenotype that resembles various aspects of caloric restriction. In C. elegans, the available data on life span extension is controversial. Therefore, the aim of this study was to determine the role of the C. elegans INDY homolog CeNAC2 in life span regulation and to delineate possible molecular mechanisms. siRNA against Indy/CeNAC2 was used to reduce expression of Indy/CeNAC2. Mean life span was assessed in four independent experiments, as well as whole body fat content and AMPK activation. Moreover, the effect of Indy/CeNAC2 knockdown in C. elegans with inactivating variants of AMPK (TG38) was studied. Knockdown of Indy/CeNAC2 increased life span by 22±3 % compared to control siRNA treated C. elegans, together with a decrease in whole body fat content by ~50%. Indy/CeNAC2 reduction also increased the activation of the intracellular energy sensor AMPK/aak2. In worms without functional AMPK/aak2, life span was not extended when Indy/CeNAC2 was reduced. Inhibition of glycolysis with deoxyglucose, an intervention known to increase AMPK/aak2 activity and life span, did not promote longevity when Indy/CeNAC2 was knocked down. Together, these data indicate that reducing the expression of Indy/CeNAC2 increases life span in C. elegans, an effect mediated at least in part by AMPK/aak2

Renal function is independently associated with circulating betatrophin

OBJECTIVE: Betatrophin has been identified as a marker linking liver with beta cell function and lipid metabolism in murine models. Until now, the regulation of circulating betatrophin in humans is not entirely clear. We here analyzed the relation of betatrophin levels to phenotypes of the metabolic syndrome and speculated that renal function might influence circulating betatrophin levels and explain age-dependent changes of betatrophin. SUBJECTS: We analyzed blood samples from 535 individuals participating in the Metabolic Syndrome Berlin Potsdam study. RESULTS: In a crude analysis we found a positive correlation between betatrophin levels and HbA1c (r = 0.24; p < 0.001), fasting glucose (r = 0.20; p < 0.001) and triglycerides (r = 0.12; p = 0.007). Furthermore betatrophin was positively correlated with age (r = 0.47; p <0.001), systolic blood pressure (r = 0.17; p < 0.001), intima media thickness (r = 0.26; p < 0.001) and negatively correlated with CKD-EPI eGFR (r = -0.33; p < 0.001) as an estimate of renal function. Notably, eGFR remained highly associated with betatrophin after adjustment for age, waist circumference, gender, HbA1c and lipid parameters in a multivariate linear regression model ({beta} = -0.197, p< 0.001). CONCLUSIONS: Our data suggest that circulating levels of betatrophin depend on age, gender, waist circumference, total/HDL cholesterol ratio and renal function. Especially the association to eGFR highlights the importance for future studies to address renal function as possible influence on betatrophin regulation and consider eGFR as potential confounder when analyzing the role of betatrophin in humans

Search for composite and exotic fermions at LEP 2

A search for unstable heavy fermions with the DELPHI detector at LEP is reported. Sequential and non-canonical leptons, as well as excited leptons and quarks, are considered. The data analysed correspond to an integrated luminosity of about 48 pb^{-1} at an e^+e^- centre-of-mass energy of 183 GeV and about 20 pb^{-1} equally shared between the centre-of-mass energies of 172 GeV and 161 GeV. The search for pair-produced new leptons establishes 95% confidence level mass limits in the region between 70 GeV/c^2 and 90 GeV/c^2, depending on the channel. The search for singly produced excited leptons and quarks establishes upper limits on the ratio of the coupling of the excited fermio

Search for lightest neutralino and stau pair production in light gravitino scenarios with stau NLSP

Promptly decaying lightest neutralinos and long-lived staus are searched for in the context of light gravitino scenarios. It is assumed that the stau is the next to lightest supersymmetric particle (NLSP) and that the lightest neutralino is the next to NLSP (NNLSP). Data collected with the Delphi detector at centre-of-mass energies from 161 to 183 \GeV are analysed. No evidence of the production of these particles is found. Hence, lower mass limits for both kinds of particles are set at 95% C.L.. The mass of gaugino-like neutralinos is found to be greater than 71.5 GeV/c^2. In the search for long-lived stau, masses less than 70.0 to 77.5 \GeVcc are excluded for gravitino masses from 10 to 150 \eVcc . Combining this search with the searches for stable heavy leptons and Minimal Supersymmetric Standard Model staus a lower limit of 68.5 \GeVcc may be set for the stau mas

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

Impact of Type 2 Diabetes Susceptibility Variants on Quantitative Glycemic Traits Reveals Mechanistic Heterogeneity

Patients with established type 2 diabetes display both β-cell dysfunction and insulin resistance. To define fundamental processes leading to the diabetic state, we examined the relationship between type 2 diabetes risk variants at 37 established susceptibility loci, and indices of proinsulin processing, insulin secretion, and insulin sensitivity. We included data from up to 58,614 nondiabetic subjects with basal measures and 17,327 with dynamic measures. We used additive genetic models with adjustment for sex, age, and BMI, followed by fixed-effects, inverse-variance meta-analyses. Cluster analyses grouped risk loci into five major categories based on their relationship to these continuous glycemic phenotypes. The first cluster (PPARG, KLF14, IRS1, GCKR) was characterized by primary effects on insulin sensitivity. The second cluster (MTNR1B, GCK) featured risk alleles associated with reduced insulin secretion and fasting hyperglycemia. ARAP1 constituted a third cluster characterized by defects in insulin processing. A fourth cluster (TCF7L2, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was defined by loci influencing insulin processing and secretion without a detectable change in fasting glucose levels. The final group contained 20 risk loci with no clear-cut associations to continuous glycemic traits. By assembling extensive data on continuous glycemic traits, we have exposed the diverse mechanisms whereby type 2 diabetes risk variants impact disease predisposition

Investigation of the splitting of quark and gluon jets

The splitting processes in identified quark and gluon jets are investigated using longitudinal and transverse observables. The jets are selected from symmetric three-jet events measured in Z decays with the Delphi detector in 1991-1994. Gluon jets are identified using heavy quark anti-tagging. Scaling violations in identified gluon jets are observed for the first time. The scale energy dependence of the gluon fragmentation function is found to be about two times larger than for the corresponding quark jets, consistent with the QCD expectation TeX . The primary splitting of gluons and quarks into subjets agrees with fragmentation models and, for specific regions of the jet resolution TeX , with NLLA calculations. The maximum of the ratio of the primary subjet splittings in quark and gluon jets is TeX . Due to non-perturbative effects, the data are below the expectation at small TeX . The transition from the perturbative to the non-perturbative domain appears at smaller TeX for quark jets than for gluon jets. Combined with the observed behaviour of the higher rank splittings, this explains the relatively small multiplicity ratio between gluon and quark jets

Measurement of the Quark and Gluon Fragmentation Functions in Z0Z^0 Hadronic Decays

The fragmentation functions and multiplicities in $b\overline{b}$ and light quark events are compared. The measured transverse and longitudinal components of the fragmentation function allow the gluon fragmentation function to be evaluated

Search for scalar fermions and long-lived scalar leptons at centre-of-mass energies of 130 GeV to 172 GeV

Data taken by DELPHI during the 1995 and 1996 LEP runs have been used to search for the supersymmetric partners of electron, muon and tau leptons and of top and bottom quarks. The observations are in agreement with standard model predictions. Limits are set on sfermion masses. Searches for long lived scalar leptons from low scale supersymmetry breaking models exclude stau masses below 55~GeV/c$^2$ at the 95\% confidence level, irrespective of the gravitino mass

Measurement of Trilinear Gauge Couplings in e+e−e^+ e^- Collisions at 161 GeV and 172 GeV

Trilinear gauge boson couplings are measured using data taken by DELPHI at 161~GeV and 172~GeV. Values for $WWV$ couplings ($V=Z, \gamma$) are determined from a study of the reactions \eeWW\ and \eeWev, using differential distributions from the $WW$ final state in which one $W$ decays hadronically and the other leptonically, and total cross-section data from other channels. Limits are also derived on neutral $ZV\gamma$ couplings from an analysis of the reaction \eegi