A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Impacts of Environmental Motion on CDC2 Expression and Cell Growth in Tetrahymena thermophila

In this experiment, the eect of constant motion on expression of the cell cycle control gene CDC2 was examined in the organism Tetrahymena thermophila. We hypothesized that CDC2 expression would decrease with a corresponding increase in movement within the Tetrahymena culture environment. The CDC2 protein is primarily used in the replication of eukaryotic DNA because of its connection to HHO1, an important factor in transcriptional regulation. If the cells were subject to vegetative growth in which there are no stressors put on the cell, then HHO1 becomes phosphorylated to prevent it from interacting with chromatin. Because CDC2 is important in facilitating the phosphorylation of the HHO1, we hypothesized that, during vegetative growth, there would likely be an increase in the expression of CDC2. Moreover, when the cell is subject to stressors there would be no need to control cell growth by phosphorylating HHO1, so CDC2 expression should decrease. To address this hypothesis, Tetrahymena thermophila were randomly assigned to a control group, which was cultured under normal lab-growth conditions, or a treatment group, which was subjected to constant movement on an orbital shaker for a period of one week. Following treatment, RNA extraction, reverse transcription, and gene-specific PCR (including gel electrophoresis) were used to analyze CDC2 expression in both the control and treatment groups. Furthermore, the growth rate of both groups was analyzed using a hemocytometer. We predicted that Tetrahymena cells subjected to constant motion would exhibit a decrease in cell growth rate and expression of CDC2

The dynamic influence of social capital on the international growth of new ventures

This paper explores the origin, evolution, and appropriation of social capital by new ventures seeking international growth. Using longitudinal case studies in the software industry, we model the dynamic influence of social capital on new venture internationalization. We theorize that new ventures of founders from a globally-connected environment, such as with return migration or MNC experience, have higher stocks of initial social capital than others. We provide a nuanced analysis of the dynamic processes involved in the evolution of social capital, and highlight the mechanisms of decay and replenishment over time. Network learning plays a critical role in new ventures' ability to realize the potential contribution of social capital to international growth

Pulmonary complications in patients with staphylococcal sepsis

Background: The aim of the present study was to determine the pulmonary findings in patients with sepsis caused by Staphylococcus aureus