Multi-Ethnic Analysis of Lipid-Associated Loci: The NHLBI CARe Project

Background: Whereas it is well established that plasma lipid levels have substantial heritability within populations, it remains unclear how many of the genetic determinants reported in previous studies (largely performed in European American cohorts) are relevant in different ethnicities. Methodology/Principal Findings: We tested a set of $\sim$50,000 polymorphisms from $\sim$2,000 candidate genes and genetic loci from genome-wide association studies (GWAS) for association with low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) in 25,000 European Americans and 9,000 African Americans in the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe). We replicated associations for a number of genes in one or both ethnicities and identified a novel lipid-associated variant in a locus harboring ICAM1. We compared the architecture of genetic loci associated with lipids in both African Americans and European Americans and found that the same genes were relevant across ethnic groups but the specific associated variants at each gene often differed. Conclusions/Significance: We identify or provide further evidence for a number of genetic determinants of plasma lipid levels through population association studies. In many loci the determinants appear to differ substantially between African Americans and European Americans

Emerging Roles of PAR-1 and PAFR in Melanoma Metastasis

Melanoma growth, angiogenesis and metastatic progression are strongly promoted by the inflammatory tumor microenvironment due to high levels of cytokine and chemokine secretion by the recruited inflammatory and stromal cells. In addition, platelets and molecular components of procoagulant pathways have been recently emerging as critical players of tumor growth and metastasis. In particular, thrombin, through the activity of its receptor protease-activated receptor-1 (PAR-1), regulates tumor cell adhesion to platelets and endothelial cells, stimulates tumor angiogenesis, and promotes tumor growth and metastasis. Notably, in many tumor types including melanoma, PAR-1 expression directly correlates with their metastatic phenotype and is directly responsible for the expression of interleukin-8, matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor, platelet-derived growth factor, and integrins. Another proinflammatory receptor–ligand pair, platelet-activating factor (PAF) and its receptor (PAFR), have been shown to act as important modulators of tumor cell adhesion to endothelial cells, angiogenesis, tumor growth and metastasis. PAF is a bioactive lipid produced by a variety of cells from membrane glycerophospholipids in the same reaction that releases arachidonic acid, and can be secreted by platelets, inflammatory cells, keratinocytes and endothelial cells. We have demonstrated that in metastatic melanoma cells, PAF stimulates the phosphorylation of cyclic adenosine monophosphate response element-binding protein (CREB) and activating transcription factor 1 (ATF-1), which results in overexpression of MMP-2 and membrane type 1-MMP (membrane type 1-MMP). Since only metastatic melanoma cells overexpress CREB/ATF-1, we propose that metastatic melanoma cells are better equipped than their non-metastatic counterparts to respond to PAF within the tumor microenvironment. The evidence supporting the hypothesis that the two G-protein coupled receptors, PAR-1 and PAFR, contribute to the acquisition of the metastatic phenotype of melanoma is presented and discussed

Blood pressure and hypertension in people living at high altitude in Nepal

This study aimed to describe blood pressure (BP) and hypertension (HT) in samples of high altitude populations of Nepal and to explore associations of systolic BP, diastolic BP and HT with altitude. This was a cross-sectional survey among 521 people living at four different altitude levels, all above 2800 m, in the Mustang and Humla districts of Nepal. Data on BP was available for all 521 participants. Systolic and diastolic BP levels were highest at the altitude of 3620 m (the highest area surveyed) but did not consistently increase with altitude. Using the cut-point of ≥140/90 mmHg (systolic/diastolic), the prevalence of HT (or on anti-hypertensive medication) was 46.1%, 40.9%, and 54.5% respectively at 2800 m, 3270 m and 3620 m of Mustang district, and 29.1% at 2890 m of Humla district. In a multivariate model adjusting for potential confounders there was moderate evidence of a relationship between systolic BP and altitude; mean systolic BP increased by 14.1 mmHg (95% CI 2.6 to 25.5), P=0.02 for every 1000 m elevation. Although diastolic BP and the probability for HT (or on anti-hypertensive medication) also tended to increase with increasing altitude levels, there was no evidence of a relationship. In the present study three out of four communities living at higher altitude levels showed a greater prevalence of HT among those aged 30 years or older compared with the overall national data. These findings indicate a probable high risk of raised BP in high altitude populations in Nepal

Genetic variants associated with fasting blood lipids in the U.S. population: Third National Health and Nutrition Examination Survey

<p>Abstract</p> <p>Background</p> <p>The identification of genetic variants related to blood lipid levels within a large, population-based and nationally representative study might lead to a better understanding of the genetic contribution to serum lipid levels in the major race/ethnic groups in the U.S. population.</p> <p>Methods</p> <p>Using data from the second phase (1991-1994) of the Third National Health and Nutrition Examination Survey (NHANES III), we examined associations between 22 polymorphisms in 13 candidate genes and four serum lipids: high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG). Univariate and multivariable linear regression and within-gene haplotype trend regression were used to test for genetic associations assuming an additive mode of inheritance for each of the three major race/ethnic groups in the United States (non-Hispanic white, non-Hispanic black, and Mexican American).</p> <p>Results</p> <p>Variants within <it>APOE </it>(rs7412, rs429358), <it>PON1 </it>(rs854560), <it>ITGB3 </it>(rs5918), and <it>NOS3 </it>(rs2070744) were found to be associated with one or more blood lipids in at least one race/ethnic group in crude and adjusted analyses. In non-Hispanic whites, no individual polymorphisms were associated with any lipid trait. However, the <it>PON1 </it>A-G haplotype was significantly associated with LDL-C and TC. In non-Hispanic blacks, <it>APOE </it>variant rs7412 and haplotype T-T were strongly associated with LDL-C and TC; whereas, rs5918 of <it>ITGB3 </it>was significantly associated with TG. Several variants and haplotypes of three genes were significantly related to lipids in Mexican Americans: <it>PON1 </it>in relation to HDL-C; <it>APOE </it>and <it>NOS3 </it>in relation to LDL-C; and <it>APOE </it>in relation to TC.</p> <p>Conclusions</p> <p>We report the significant associations of blood lipids with variants and haplotypes in <it>APOE</it>, <it>ITGB3, NOS3</it>, and <it>PON1 </it>in the three main race/ethnic groups in the U.S. population using a large, nationally representative and population-based sample survey. Results from our study contribute to a growing body of literature identifying key determinants of plasma lipoprotein concentrations and could provide insight into the biological mechanisms underlying serum lipid and cholesterol concentrations.</p

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Not AvailableDe-oiled rice bran (DORB) is obtained after oil is removed from the rice bran. This is the commonly used ingredient in the feeding of Indian major carps due to its cheaper cost. DORB is used as a feed ingredient in cattle, poultry, and fish diet. Along with this, they are also used in making fiber-rich biscuits and extraction of an antioxidant compound like oryzanol and other industrial uses. Due to the increased competition, there will be a huge imbalance in the demand and supply for this ingredient in the years to come. DORB is associated with high fiber content, anti-nutrients, and non-starch polysaccharides which lead to its poor utilization resulting in a higher feed conversion ratio (FCR) in fish. Hence, the strategic utilization of this ingredient by solid-state fermentation, exogenous enzyme supplementation, and supplementing it with deficient nutrients like amino acids and fatty acids will help in improving the utilization of this ingredient.Not Availabl

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Not AvailableThe study determined the combined effect of dietary l- carnitine (non- essential organic nutrient) and ractopamine (feed additive) on growth performance and nu-tritional composition of Labeo calbasu. To ascertain this, a 60-day feeding trial was carried out under a controlled condition where two hundred and twenty-five healthy L. calbasu fingerlings (avg. wt. 3.47 ± 0.1 g) were divided into four treatments group and one control group in triplicate. Therefore, the respective combination of l- carnitine and ractopamine diet was fed to L. calbasu fingerlings as C: control or basal feed without l- carnitine and ractopamine; T1:1 g kg−1l- carnitine and 10 mg kg−1 rac-topamine; T2: 2 g kg−1l- carnitine and 20 mg kg−1 ractopamine; T3: 3 g kg−1l- carnitine and 30 mg kg−1 ractopamine and T4: 4 g kg−1l- carnitine and 40 mg kg−1 ractopamine, respectively. Upon completion of the 60-day feeding experiment, eight fish were randomly collected from each tank and subjected to a series of laboratory analyses. The study determines that T2 group fish significantly (p< .05) improved the WGP (244.66± 20.59%), SGR (0.89 ± 0.04), PER (2.20 ± 0.14) and increased crude protein content in fish muscle. In addition, many essential amino acids were recorded signifi-cantly high (p< .05) in the fish fed with diet T2 compared with others. Hence, dietary supplementation of l- carnitine and ractopamine at 2 g kg−1 and 20 mg kg−1 in combi-nation is beneficial for growth and nutritional composition of L. calbasu.Not Availabl

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Not AvailableA 60-day feeding trial was conducted to study the effect of exogenous enzymes (xylanase and phytase) supplementation in the non-fermented and fermented de-oiled rice bran (DORB)-based diet of Labeo rohita. Four test diets (T1-DORB-based diet, T2-fermented DORB-based diet, T3-phytase and xylanase supplemented DORB-based diet, and T4-phytase and xylanase supplemented fermented DORB-based diet) were formulated and fed to the respective groups. Test diets T3 and T4 were supplemented with 0.01% xylanase (16,000 U kg-1) and 0.01% phytase (500 U kg-1) enzymes. One hundred twenty juveniles of L. rohita, with an average weight 5.01 ± 0.02 g, were stocked in 12 uniform size plastic rectangular tanks in triplicate with 10 fishes per tank following a completely randomized design (CRD). Exogenous enzyme supplementation to the T3 group significantly improved the growth performance of L. rohita (p 0.05). Based on the results of the present study, it is concluded that exogenous enzyme supplementation significantly increases the growth of fish fed with DORB-based diet.Not Availabl

A structural and spectroscopic investigation of reduced graphene oxide under high pressure

The effect of high pressure on reduced graphene oxide (RGO) has been investigated using X-ray diffraction (XRD) and infrared (IR) absorption spectroscopy. Our XRD measurements show two-step reversible compression in the inter-layer spacing of RGO whereas intra-layer ordering exhibits a high pressure behavior similar to that of graphite up to 20 GPa. The line shape analysis of (100) peak, representing the intra-layer ordering, suggests presence of local out of plane distortions in RGO in the form of puckered regions which progressively straighten out as a function of pressure. IR measurements show reversible changes in spectroscopic features attributed to remnant functional groups in the inter-layer region. These measurements suggest high stability and recovering ability of RGO under pressure cycling. (C) 2014 Elsevier Ltd. All rights reserved