Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

Same data, different conclusions: Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis

In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists’ gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for organizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed

New records of sipunculan worms from Taiwan

Sipunculan worms occurring in Taiwanese waters were studied, and 11 species are recorded for the first time. They are: Sipunculidae - Sipunculus (Sipunculus) robustus Keferstein, Siphonosoma funafuti (Shipley), S. vastum (Selenka and Bulow); Golfingiidae - Golfingia (Golfingia) margaritacea margaritacea (Sars), G. muricaudata (Southern), Thysanocardia nigra (Ikeda); Themistidae - Themiste (Lagenopsis) minor minor (Ikeda); Phascolosomatidae - Phascolosoma arcuatum (Gray), P. glabrum glabrum (Sluiter); Aspidosiphonidae - Aspidosiphon (Aspidosiphon) muelleri Diesing, and Aspidosiphon (Paraspidosiphon) coyi de Quatrefages. This makes a total number of 29 species now known from this geographic region

Ischemia/reperfusion-induced changes of hypothalamic-pituitary-adrenal (HPA) activity is opioid related in Sprague-Dawley rat

The interrelationship between the hypothalamic-pituitary-adrenal (HPA) activity and expression of central opioids is determined in ischemic Sprague-Dawley rats to support the therapeutic role of naloxone against cerebral ischemia. Two-month old rats received bilateral common carotid artery occlusion plus unilateral (right side) middle cerebral artery occlusion for 90 min under the anesthesia, and followed by reperfusion for various times. The plasma contents of adrenocorticotropin (ACTH) and RNA expression levels of proopiomelanocortin (POMC) were then determined in ischemic rats with or without naloxone treatment. Results showed that ischemia stimulates but reperfusion suppresses the activity of HPA axis. The induced expression of POMC at striatum and cortex areas appears to suppress the release of ACTH from the HPA axis. The suppression on the other hand is prevented by naloxone. (C) 2003 Published by Elsevier Ireland Ltd

Attenuation of lipopolysaccharide-induced acute lung injury by treatment with IL-10

The aim of this study was to characterize the changes in neutrophils and cytokines in BAL fluid following acute lung injury (ALI), and to determine the protective effect of post-injury treatment with IL-10. A rat model of ALI was established by evenly spraying LPS (16 mg/kg) into the lungs followed by observation for 48 h. Histological changes and the kinetics of neutrophil infiltration were evaluated in the injured lungs. The cytokines (TNF-alpha, IL-6, IL-10 and interferon-gamma) and macrophage-inflammatory protein (MIP-2) were measured in BAL fluid by ELISA. The activation of BAL fluid neutrophils was investigated after treatment with IL-10 in vitro. The protective effect on histology and MIP-2 levels of intra-tracheal instillation of IL-10 12 and 16 h after LPS treatment was studied in vivo. Intra-tracheal instillation of LPS caused significant lung injury and the activation of neutrophils. The levels of TNF-alpha and IL-6 in BAL fluid peaked at 8 and 16 h after LPS instillation respectively. IL-10 levels reached a maximum at 16-24 h, at the beginning of resolution of tissue injury. IL-10 inhibited the activation of neutrophils in vitro and MIP-2 induction in vivo. IL-10 had a protective effect if it was administered 12 but not 16 h after LPS. Neutrophils appeared to play an important role in ALI. Time-dependent treatment with IL-10 after intra-tracheal instillation of LPS was effective in protecting rats from ALI, probably by suppressing pulmonary infiltration with activated neutrophils

Peroxisome proliferator-activated receptor gamma (PPAR gamma) plays a critical role in the development of TGF beta resistance of H460 cell

The primary goal of the study was to investigate how peroxisome proliferator-activated receptor gamma (PPAR gamma) played a critical role in the protection of H460 cell, one of the non-small cell lung cancer (NSCLC) cells with multidrug resistance, from transforming growth factor beta (TGF beta)-mediated mitoinhibition. In the study. TGF beta resistance of H460 cell was first confirmed by analyses of PPAR gamma expression, its interaction with TGF beta-induced Smad3 and phospho-Smad3 (p-Smad3) and survival of H460. Results showed that enable to escape from G2/M phase arrest. H460 cell had higher resistance to TGF beta-mediated mitoinhibition than CH27 (a drug sensitive control). TGF beta significantly increased PPAR gamma expression of H460 but not of CH27 cell whereas nuclear accumulation of p-Smad3 was only limited to CH27, the latter was believed to contribute to the induction P(21) (waf1/cip1) and cyclin B1, cell cycle arrest at G2/M phase and TGF beta-mediated mitoinhibition of CH27 cell. TGF beta-incluced PPAR gamma of H460 cell was further demonstrated to bind to Smad3 and p-Smad3, and GW9662 (PPAR gamma inhibitor) or PPAR gamma-specific shRNA could disrupt the binding. GW9662 also increased the nuclear accumulation of p-Smad3 that eventually led to the reduction of TGF beta resistance of H460. A transient knockdown of PPAR gamma with shRNA revealed a similar effect as GW9662. In addition, activation of P(38) instead of ERK played a critical role in TGF beta-induced expression of PPAR gamma. which subsequently activated RhoA in H460 cell. (C) 2011 Elsevier Inc. All rights reserved