Genome-wide association study of body fat distribution traits in Hispanics/Latinos from the HCHS/SOL

Central obesity is a leading health concern with a great burden carried by ethnic minority populations, especially Hispanics/Latinos. Genetic factors contribute to the obesity burden overall and to inter-population differences. We aimed to identify the loci associated with central adiposity measured as waist-to-hip ratio (WHR), waist circumference (WC) and hip circumference (HIP) adjusted for body mass index (adjBMI) by using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL); determine if differences in associations differ by background group within HCHS/SOL and determine whether previously reported associations generalize to HCHS/SOL. Our analyses included 7472 women and 5200 men of mainland (Mexican, Central and South American) and Caribbean (Puerto Rican, Cuban and Dominican) background residing in the USA. We performed genome-wide association analyses stratified and combined across sexes using linear mixed-model regression. We identified 16 variants for waist-to-hip ratio adjusted for body mass index (WHRadjBMI), 22 for waist circumference adjusted for body mass index (WCadjBMI) and 28 for hip circumference adjusted for body mass index (HIPadjBMI), which reached suggestive significance (P < 1 × 10-6). Many loci exhibited differences in strength of associations by ethnic background and sex. We brought a total of 66 variants forward for validation in cohorts (N = 34 161) with participants of Hispanic/Latino, African and European descent. We confirmed four novel loci (P < 0.05 and consistent direction of effect, and P < 5 × 10-8 after meta-analysis), including two for WHRadjBMI (rs13301996, rs79478137); one for WCadjBMI (rs3168072) and one for HIPadjBMI (rs28692724). Also, we generalized previously reported associations to HCHS/SOL, (8 for WHRadjBMI, 10 for WCadjBMI and 12 for HIPadjBMI). Our study highlights the importance of large-scale genomic studies in ancestrally diverse Hispanic/Latino populations for identifying and characterizing central obesity susceptibility that may be ancestry-specific

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap

Fasting stimulates tuberoinfundibular dopaminergic neuronal activity and inhibits prolactin secretion in oestrogen-primed ovariectomized rats: involvement of orexin A and neuropeptide Y.

[[abstract]]Fasting up-regulates central orexigenic systems including orexin A and neuropeptide Y (NPY) and it also inhibits the secretion of prolactin. We hypothesized that fasting may act through orexin A and NPY to influence tuberoinfundibular dopaminergic (TIDA) neurones, the major regulator of prolactin secretion. The effects of orexin A and NPY on TIDA neuronal activity and prolactin secretion were determined in oestrogen-primed ovariectomized rats, and the effects of fasting and the involvement of orexin A and NPY were tested. Orexin A, NPY and its analogs were administered through preimplanted intracerebroventricular (i.c.v.) cannulae. TIDA neuronal activity was determined by measuring concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) or 3,4-dihydroxyphenylalanine in the median eminence. i.c.v. injection of NPY (10 microg) or orexin A (1 microg) concomitantly increased median eminence DOPAC and decreased serum prolactin concentrations. The effect of NPY was mimicked by a Y1 receptor agonist at lower doses (0.1 and 1 microg) and no additive effect was observed when orexin A and the Y1 agaonist were coadministered. Moreover, a Y1 receptor antagonist, BIBP, not only blocked the effect of Y1 agaonist, but also that of orexin A. Treatment with BIBP alone decreased median eminence DOPAC and increased serum prolactin concentrations, indicating that endogenous NPY may play a role. Moreover, fasting for 48 h significantly increased TIDA neuronal activity, both in the morning and afternoon, and the effect was reversed by treatment with either BIBP or an antibody against orexin A. The findings support our hypothesis that fasting stimulates TIDA neuronal activity and inhibits prolactin secretion through up-regulated central orexin A and NPY systems

Development and validation of machine learning-based risk prediction models of oral squamous cell carcinoma using salivary autoantibody biomarkers.

The incidence of oral cavity squamous cell carcinoma (OSCC) continues to rise. OSCC is associated with a low average survival rate, and most patients have a poor disease prognosis because of delayed diagnosis. We used machine learning techniques to predict high-risk cases of OSCC by using salivary autoantibody levels and demographic and behavioral data. We collected the salivary samples of patients recruited from a teaching hospital between September 2008 and December 2012. Ten salivary autoantibodies, sex, age, smoking, alcohol consumption, and betel nut chewing were used to build prediction models for identifying patients with a high risk of OSCC. The machine learning algorithms applied in the study were logistic regression, random forest, support vector machine with the radial basis function kernel, eXtreme Gradient Boosting (XGBoost), and a stacking model. We evaluated the performance of the models by using the area under the receiver operating characteristic curve (AUC), with simulations conducted 100 times. A total of 337 participants were enrolled in this study. The best predictive model was constructed using a stacking algorithm with original forms of age and logarithmic levels of autoantibodies (AUC = 0.795 ± 0.055). Adding autoantibody levels as a data source significantly improved the prediction capability (from 0.698 ± 0.06 to 0.795 ± 0.055, p &lt; 0.001). We successfully established a prediction model for high-risk cases of OSCC. This model can be applied clinically through an online calculator to provide additional personalized information for OSCC diagnosis, thereby reducing the disease morbidity and mortality rates

Secure authentication policy with evidential signature scheme for WLAN

Non-repudiation is one of most important security services in electronic transactions. It provides protection from denial by one of the entities involved in a communication of parties participating in all or part of communication. In practice, a non-repudiation property is an important evidence for accounting for or tracking a system or tracking to illegal connections. However, a password-based communication system does not provide the non-repudiation property for connection evidence. In this paper, a dynamic session key policy (DSKP) with a non-repudiation signature scheme for secure mobile networks authentication is proposed. The proposed non-repudiation signature scheme is a mixed method which combines a one-way hash function and a traditional digital signature technique. Since computational cost usually is an important issue in a mobile environment, the proposed scheme can provide additional non-repudiation properties satisfying the future needs of electronic evidences such as accounting, auditing, logging, and tracking of connections to a mobile network system at the expense of a small additional computing load for the mobile devices. Besides, it can also achieve the same security services from a security and performance analysis point of view. Copyright (C) 2008 John Wiley & Sons, Ltd

Plasticity enhancement of Zr-based bulk metallic glasses by direct current electropulsing

Direct current electropulsing was used to improve the plasticity of (Zr53Cu30Ni9Al8)(99.5)Si-0.5 bulk metallic glasses. After the electropulsing treatment, the specimen showed reductions in both the glass transition and the crystallization temperatures while retaining its amorphous structure, and both Young's modulus and the hardness decreased while the nanoindentation loading curve became more serrated. Using the bond-interface method and Vickers indentation, the treated specimen showed more branching of semicircular shear bands and less radial shear bands compared to its as-cast counterpart. The possible plasticity enhancement mechanism of the electropulsing treatment was also discussed. (C) 2012 Elsevier B. V. All rights reserved

Microbending losses in double-coated optical fibers caused by axial strain-induced creep deformation of polymeric coatings

The viscoelastic behavior of commercial UV-cured polymeric coatings of optical fibers is evaluated using dynamic mechanic analysis. The results indicate that relaxation of stresses and/or strains in these coatings occurs by creep deformation. The axial strain-induced viscoelastic stresses in optical fibers are derived from the exact viscoelastic behavior of the polymeric coatings. Compressive radial stress on the glass fiber produces microbending losses, and therefore, microbending losses in double-coated optical fibers that are caused by axial strain-induced creep deformation of polymeric coatings are investigated. These microbending losses can be minimized by suitably selecting the thickness and physical properties of the polymeric coatings, as follows. The radius, Poisson's ratio, and strain ratio of the primary coating should be increased, but the Young's modulus and relaxation time of the primary coating should be decreased. The radius, Young's modulus, Poisson's ratio, and strain ratio of the secondary coating should be decreased, but the relaxation time of the secondary coating should be increased. When the thickness and physical properties of the polymeric coating are chosen to minimize the microbending loss, the thickness and Young's modulus of the secondary coatings should be large enough to withstand an external mechanical force. (C) 2010 American Institute of Physics. [doi :10.1063/1.3481094

The conditioned enhancement of neutrophil activity is catecholamine dependent

Neutrophil activity was elevated in the conditioned mice for the first time through an established conditioned training process. Catecholamines were proved to be important in the regulation of this conditioned innate immunity. In the study, the camphor odor (as the conditioned stimulus, CS) and poly I: C (as the unconditioned stimulus, US) was used to conditionally elevate the activity of the splenic neutrophils. The mechanism(s) responsible for the conditioned enhancement of neutrophil activity was further investigated using the neurochemical blocking assay and immunohistochemical analysis. Results showed that the neutrophil activity was significantly enhanced through the conditioned training process; both reserpine and 6-hydroxydopamine (6-OHDA) significantly blocked this conditioned innate immunity at the conditioned recall stage. Dexamethasone (Dex), however, showed no effect on the conditioned neutrophil response. Tyrosine hydroxylase (TH)-positive cells significantly increased in the locus coeruleus (LC), hypothalamus, and cortex but not in the spleen of the conditioned animals. These results indicate that during the conditioned recall stage, the brain signals the splenic neutrophils via the sympathetic nervous system (SNS) by releasing the peripheral catecholamines in spleen. The activation of the SNS, on the other hand, is also under the influence of catecholamines released in the LC. The hypothalamic pituitary (HP) axis, on the other hand, plays no role in the regulation of the conditioned neutrophil response. (C) 2004 Elsevier B.V. All rights reserved