New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Influence of Dietary Supplementation of Propolis and Bee Pollen on Liver Pathology in Broiler Chickens

One of the major problems in intensive breeding of chickens is liver damage. The objective of this study was to determine the influence of dietary supplementation with propolis and bee pollen on liver pathology in broiler chickens. The study was conducted on 200 Ross 308 chickens equally distributed by sex that were divided into five groups. Throughout the whole study, the control group of chickens was fed with a basal diet, while the experimental groups of chickens were fed with the same diet further supplemented with propolis and bee pollen, each supplement given separately or in combination in a certain proportion. The study showed that the clusters of lymphocytes in the hepatocytes, the vacuolar degeneration and necrosis of the liver parenchyma, the bile ductule hyperplasia, and the various forms of pathological changes in the liver arteries and veins were more frequent in liver tissue samples of the control group compared to liver tissue samples of all the experimental groups (p &lt; 0.001). The study further showed that all the previously mentioned histopathological lesions of liver tissue were always more extensive in the liver tissue samples of the control group than in the liver tissue samples of all the experimental groups (p &lt; 0.001). The supplementation of broiler chickens with propolis and/or bee pollen has a strong protective effect on liver pathology in broiler chickens

Relación entre los conceptos de creatividad y psicosis en la obra de Winnicott

El proyecto tiene por objetivo investigar el lugar de la creatividad y la psicosis en la obra de Winnicott, buscando relaciones entre ambos conceptos. Winnicott ubicaba la creatividad dentro de la experiencia cultural llevada a cabo en un espacio potencial que no está ni adentro ni afuera del sujeto. Es la conservación en la vida adulta de algo que se origina en la infancia. Es primaria y universal. En este espacio el sujeto se encuentra libre de tensiones. Esta tercera área de experiencias humanas no se dedica exclisivamente ni a la fantasía subjetiva ni al conocimiento objetivo, sino que se ocupa de una mezcla de ambos. Según Winnicott, la psicosis, al igual que la creatividad, se origina en la infancia. Es una perturbación en la estructuración de la personalidad por fallas en la asistencia temprana del niño, que no le permiten usar adecuadamente el objeto transicional, quedando este vacío de significado. Winnicott entiende a la psicosis como una organización defensiva surgida para evitar un tipo de angustia califcada de impensable. La creatividad implica un estado de no integración que el individuo debe soportar. El psicótico, al eregir defensas contra la desintegración, no es capaz de llevar una vida creativa.Fil: Klaric, Ivana. Facultad de Psicología. Universidad Nacional de Mar del Plata; ArgentinaFil: Sacco, Marcela Julia. Facultad de Psicología. Universidad Nacional de Mar del Plata; ArgentinaFil: Elgart, Ana Valeria. Facultad de Psicología. Universidad Nacional de Mar del Plata; Argentin

Influence of Dietary Supplementation of Propolis and Bee Pollen on Liver Pathology in Broiler Chickens

One of the major problems in intensive breeding of chickens is liver damage. The objective of this study was to determine the influence of dietary supplementation with propolis and bee pollen on liver pathology in broiler chickens. The study was conducted on 200 Ross 308 chickens equally distributed by sex that were divided into five groups. Throughout the whole study, the control group of chickens was fed with a basal diet, while the experimental groups of chickens were fed with the same diet further supplemented with propolis and bee pollen, each supplement given separately or in combination in a certain proportion. The study showed that the clusters of lymphocytes in the hepatocytes, the vacuolar degeneration and necrosis of the liver parenchyma, the bile ductule hyperplasia, and the various forms of pathological changes in the liver arteries and veins were more frequent in liver tissue samples of the control group compared to liver tissue samples of all the experimental groups (p &lt; 0.001). The study further showed that all the previously mentioned histopathological lesions of liver tissue were always more extensive in the liver tissue samples of the control group than in the liver tissue samples of all the experimental groups (p &lt; 0.001). The supplementation of broiler chickens with propolis and/or bee pollen has a strong protective effect on liver pathology in broiler chickens

3000 years of solitude: extreme differentiation in the island isolates of Dalmatia, Croatia

Communities with increased shared ancestry represent invaluable tools for genetic studies of complex traits. '1001 Dalmatians' research program collects biomedical information for genetic epidemiological research from multiple small isolated populations ('metapopulation') in the islands of Dalmatia, Croatia. Random samples of 100 individuals from 10 small island settlements (n<2000 inhabitants) were collected in 2002 and 2003. These island communities were carefully chosen to represent a wide range of distinct and well-documented demographic histories. Here, we analysed their genetic make-up using 26 short tandem repeat (STR) markers, at least 5 cM apart. We found a very high level of differentiation between most of these island communities based on Wright's fixation indexes, even within the same island. The model-based clustering algorithm, implemented in STRUCTURE, defined six clusters with very distinct genetic signatures, four of which corresponded to single villages. The extent of background LD, assessed with eight linked markers on Xq13-21, paralleled the extent of differentiation and was also very high in most of the populations under study. For each population, demographic history was characterised and 12 'demographic history' variables were tentatively defined. Following stepwise regression, the demographic history variable that most significantly predicted the extent of LD was the proportion of locally born grandparents. Strong isolation and endogamy are likely to be the main forces maintaining this highly structured overall population

Body mass index from age 15 years onwards and muscle mass, strength and quality in early old age: findings from the MRC National Survey of Health and Development

BACKGROUND: As more people live more of their lives obese, it is unclear what impact this will have on muscle mass, strength, and quality. We aimed to examine the associations of body mass index (BMI) from age 15 years onwards with low muscle mass, strength, and quality in early old age.METHODS: A total of 1,511 men and women from a British birth cohort study with BMI measured at 15, 20, 26, 36, 43, 53, and 60-64 years and dual-energy x-ray absorptiometry scans at 60-64 years were included. Four binary outcomes identified those in the bottom sex-specific 20% of (a) appendicular lean mass (ALM) index (kilogram per square meter), (b) ALM residuals (derived from sex-specific models in which ALM (kilogram) = ?0 + ?1 height [meter] + ?2 fat mass [kilogram]), (c) grip strength (kilogram), (d) muscle quality (grip strength [kilogram]/arm lean mass [kilogram]). Associations of BMI with each outcome were tested.RESULTS: Higher BMI from age 15 years was associated with lower odds of low ALM but higher odds of low muscle quality (per 1 SD increase in BMI at 36 years, odds ratio of low ALM residuals = 0.50 [95% CI: 0.43, 0.59], and muscle quality = 1.50 [1.29, 1.75]). Greater gains in BMI were associated with lower odds of low ALM index but higher odds of low muscle quality. BMI was not associated with grip strength.CONCLUSIONS: Given increases in the global prevalence of obesity, cross-cohort comparisons of sarcopenia need to consider our findings that greater gains in BMI are associated with higher muscle mass but not with grip strength and therefore with lower muscle quality

SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout

Uric acid is the end product of purine metabolism in humans and great apes, which have lost hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200?500 lM) compared with other mammals (3?120 lM)1. About 70% of daily urate disposal occurs via the kidneys, and in 5?25% of the human population, impaired renal excretion leads to hyperuricemia2. About 10% of people with hyperuricemia develop gout, an inflammatory arthritis that results from deposition of monosodium urate crystals in the joint. We have identified genetic variants within a transporter gene, SLC2A9, that explain 1.7?5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan in a Croatian population sample. SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in UK, Croatian and German population samples. SLC2A9 is a known fructose transporter3, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes

A genetic association study of circulating coagulation Factor VIII and von Willebrand Factor levels

Coagulation Factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are critical to coagulation and platelet aggregation. We leveraged whole genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program along with TOPMed-based imputation of genotypes in additional samples to identify genetic associations with circulating FVIII and VWF levels in a single variant meta-analysis including up to 45,289 participants. Gene-based aggregate tests were implemented in TOPMed. We identified three candidate causal genes and tested their functional effect on FVIII release from human liver endothelial cells (HLECs) and VWF release from human umbilical vein endothelial cells (HUVECs). Mendelian randomization was also performed to provide evidence for causal associations of FVIII and VWF with thrombotic outcomes. We identified associations (P&lt;5×10-9) at seven new loci for FVIII (ST3GAL4, CLEC4M, B3GNT2, ASGR1, F12, KNG1, and TREM1/NCR2) and one for VWF (B3GNT2). VWF, ABO, and STAB2 were associated with FVIII and VWF in gene-based analyses. Multi-phenotype analysis of FVIII and VWF identified another three new loci, including PDIA3. Silencing of B3GNT2 and the previously reported CD36 gene decreased release of FVIII by HLECs, while silencing of B3GNT2, CD36, and PDIA3 decreased release of VWF by HVECs. Mendelian randomization supports causal association of higher FVIII and VWF with increased risk of thrombotic outcomes. Seven new loci were identified for FVIII and one for VWF, with evidence supporting causal associations of FVIII and VWF with thrombotic outcomes. B3GNT2, CD36, and PDIA3 modulate the release of FVIII and/or VWF in vitro

Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 x 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-kappaB signaling and mitochondrial dysfunction as biological processes related to timing of menopause