HYPOGLYCEAMIC ACTIVITY OF FRACTIONS OF ETHYL ACETATE FRACTION OF THE WATER EXTRACT OF ARTOCARPUS HETEROPHYLLUS SENESCENT LEAVES

The aqueous extract of the senescent leaves of Artocarpus heterophyllus is traditionally used in Sri Lanka as a hypoglyceamic agent. It has been previously reportedthat the hypoglyceamic activity lies in the ethyl acetate fraction of the water extract (EA/W). The EA/W fraction was fractionated by chromatography on sephadex LH-20. Five fractions eluting with the following solvent systems were obtained. Fraction 1, dichloromethane/ hexane (4:1), Fraction 2, dichloromethane/acetone (3:2), Fraction 3, dichloromethane/ acetone (1:4), Fraction 4, dichloromethane/ methanol (1:1) and Fraction 5, methanol. These fractions were screened for in vivo hypoglyceamic activity. Each fraction was tested for its effect on the blood glucose levels of fasted normal and diabetic rats. None of the fractions caused hypoglyceamia on normal rats. However there was significant (p < 0.001) reduction in the blood glucose level during the first three hours after giving the fractions 3, 4 and 5 to diabetic rats. Among the three fractions fraction 4 showed the highest hypoglyceamic activity. Fractions 3, 4 and 5 were also the most active in the glucose tolerance test carried out on both normal and diabetic rats. However fraction 3 showed the highest activity in this assay. In both assays using diabetic rats fractions 3, 4 and 5 at 50 mg/kg body weight showed activity of the same order as glibenclamide at 5 mg/ kg body weight. These results maybe of potential use for the development of an anti diabetic drug from leaves of Artocarpus heterophyllus

A multivariate genome-wide association study of psycho-cardiometabolic multimorbidity

Coronary artery disease (CAD), type 2 diabetes (T2D) and depression are among the leading causes of chronic morbidity and mortality worldwide. Epidemiological studies indicate a substantial degree of multimorbidity, which may be explained by shared genetic influences. However, research exploring the presence of pleiotropic variants and genes common to CAD, T2D and depression is lacking. The present study aimed to identify genetic variants with effects on cross-trait liability to psycho-cardiometabolic diseases. We used genomic structural equation modelling to perform a multivariate genome-wide association study of multimorbidity (Neffective = 562,507), using summary statistics from univariate genome-wide association studies for CAD, T2D and major depression. CAD was moderately genetically correlated with T2D (rg = 0.39, P = 2e-34) and weakly correlated with depression (rg = 0.13, P = 3e-6). Depression was weakly correlated with T2D (rg = 0.15, P = 4e-15). The latent multimorbidity factor explained the largest proportion of variance in T2D (45%), followed by CAD (35%) and depression (5%). We identified 11 independent SNPs associated with multimorbidity and 18 putative multimorbidity-associated genes. We observed enrichment in immune and inflammatory pathways. A greater polygenic risk score for multimorbidity in the UK Biobank (N = 306,734) was associated with the co-occurrence of CAD, T2D and depression (OR per standard deviation = 1.91, 95% CI = 1.74–2.10, relative to the healthy group), validating this latent multimorbidity factor. Mendelian randomization analyses suggested potentially causal effects of BMI, body fat percentage, LDL cholesterol, total cholesterol, fasting insulin, income, insomnia, and childhood maltreatment. These findings advance our understanding of multimorbidity suggesting common genetic pathways.</p

Inhibition of somatosensory mechanotransduction by annexin A6

Mechanically activated, slowly adapting currents in sensory neurons have been linked to noxious mechanosensation. The conotoxin NMB-1 (noxious mechanosensation blocker-1) blocks such currents and inhibits mechanical pain. Using a biotinylated form of NMB-1 in mass spectrometry analysis, we identified 67 binding proteins in sensory neurons and a sensory neuron-derived cell line, of which the top candidate was annexin A6, a membrane-associated calcium-binding protein. Annexin A6-deficient mice showed increased sensitivity to mechanical stimuli. Sensory neurons from these mice showed increased activity of the cation channel Piezo2, which mediates a rapidly adapting mechano-gated current linked to proprioception and touch, and a decrease in mechanically activated, slowly adapting currents. Conversely, overexpression of annexin A6 in sensory neurons inhibited rapidly adapting currents that were partially mediated by Piezo2. Furthermore, overexpression of annexin A6 in sensory neurons attenuated mechanical pain in a mouse model of osteoarthritis, a disease in which mechanically evoked pain is particularly problematic. These data suggest that annexin A6 can be exploited to inhibit chronic mechanical pain

Intercalibration of the barrel electromagnetic calorimeter of the CMS experiment at start-up

Calibration of the relative response of the individual channels of the barrel electromagnetic calorimeter of the CMS detector was accomplished, before installation, with cosmic ray muons and test beams. One fourth of the calorimeter was exposed to a beam of high energy electrons and the relative calibration of the channels, the intercalibration, was found to be reproducible to a precision of about 0.3%. Additionally, data were collected with cosmic rays for the entire ECAL barrel during the commissioning phase. By comparing the intercalibration constants obtained with the electron beam data with those from the cosmic ray data, it is demonstrated that the latter provide an intercalibration precision of 1.5% over most of the barrel ECAL. The best intercalibration precision is expected to come from the analysis of events collected in situ during the LHC operation. Using data collected with both electrons and pion beams, several aspects of the intercalibration procedures based on electrons or neutral pions were investigated

Measurement of the p-pbar -> Wgamma + X cross section at sqrt(s) = 1.96 TeV and WWgamma anomalous coupling limits

The WWgamma triple gauge boson coupling parameters are studied using p-pbar -> l nu gamma + X (l = e,mu) events at sqrt(s) = 1.96 TeV. The data were collected with the DO detector from an integrated luminosity of 162 pb^{-1} delivered by the Fermilab Tevatron Collider. The cross section times branching fraction for p-pbar -> W(gamma) + X -> l nu gamma + X with E_T^{gamma} > 8 GeV and Delta R_{l gamma} > 0.7 is 14.8 +/- 1.6 (stat) +/- 1.0 (syst) +/- 1.0 (lum) pb. The one-dimensional 95% confidence level limits on anomalous couplings are -0.88 < Delta kappa_{gamma} < 0.96 and -0.20 < lambda_{gamma} < 0.20.Comment: Submitted to Phys. Rev. D Rapid Communication

Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt{s} = 1.96 TeV using Kinematic Characteristics of Lepton + Jets Events

We present a measurement of the top quark pair ttbar production cross section in ppbar collisions at a center-of-mass energy of 1.96 TeV using 230 pb**{-1} of data collected by the DO detector at the Fermilab Tevatron Collider. We select events with one charged lepton (electron or muon), large missing transverse energy, and at least four jets, and extract the ttbar content of the sample based on the kinematic characteristics of the events. For a top quark mass of 175 GeV, we measure sigma(ttbar) = 6.7 {+1.4-1.3} (stat) {+1.6- 1.1} (syst) +/-0.4 (lumi) pb, in good agreement with the standard model prediction.Comment: submitted to Phys.Rev.Let

Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt(s)=1.96 TeV using Lepton + Jets Events with Lifetime b-tagging

We present a measurement of the top quark pair ($t\bar{t}$) production cross section ($\sigma_{t\bar{t}}$) in $p\bar{p}$ collisions at $\sqrt{s}=1.96$ TeV using 230 pb$^{-1}$ of data collected by the D0 experiment at the Fermilab Tevatron Collider. We select events with one charged lepton (electron or muon), missing transverse energy, and jets in the final state. We employ lifetime-based b-jet identification techniques to further enhance the $t\bar{t}$ purity of the selected sample. For a top quark mass of 175 GeV, we measure $\sigma_{t\bar{t}}=8.6^{+1.6}_{-1.5}(stat.+syst.)\pm 0.6(lumi.)$ pb, in agreement with the standard model expectation.Comment: 7 pages, 2 figures, 3 tables Submitted to Phys.Rev.Let

Search for W' bosons decaying to an electron and a neutrino with the D0 detector

This Letter describes the search for a new heavy charged gauge boson W' decaying into an electron and a neutrino. The data were collected with the D0 detector at the Fermilab Tevatron proton-antiproton Collider at a center-of-mass energy of 1.96 TeV, and correspond to an integrated luminosity of about 1 inverse femtobarn. Lacking any significant excess in the data in comparison with known processes, an upper limit is set on the production cross section times branching fraction, and a W' boson with mass below 1.00 TeV can be excluded at the 95% C.L., assuming standard-model-like couplings to fermions. This result significantly improves upon previous limits, and is the most stringent to date.Comment: submitted to Phys. Rev. Let

Measurement of the ratios of the Z/G* + >= n jet production cross sections to the total inclusive Z/G* cross section in ppbar collisions at sqrt(s) = 1.96 TeV

We present a study of events with Z bosons and jets produced at the Fermilab Tevatron Collider in ppbar collisions at a center of mass energy of 1.96 TeV. The data sample consists of nearly 14,000 Z/G* -> e+e- candidates corresponding to the integrated luminosity of 0.4 fb-1 collected using the D0 detector. Ratios of the Z/G* + >= n jet cross sections to the total inclusive Z/G* cross section have been measured for n = 1 to 4 jet events. Our measurements are found to be in good agreement with a next-to-leading order QCD calculation and with a tree-level QCD prediction with parton shower simulation and hadronization.Comment: 7 pages, 2 figures, slightly modified, submitted to Phys. Lett.