Bulletin (1942-1943)

https://red.mnstate.edu/bulletins/1023/thumbnail.jp

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

Semiparametric estimators for the regression coefficients in the linear transformation competing risks model with missing cause of failure

We consider the problem of estimating the regression coefficients in a competing risks model, where the relationship between the cause-specific hazard for the cause of interest and covariates is described using linear transformation models and when cause of failure is missing at random for a subset of individuals. Using the theory of Robins et al. (1994) for missing data problems and the approach of Chen et al. (2002) for estimating regression coefficients for linear transformation models, we derive augmented inverse probability weighted complete-case estimators for the regression coefficients that are doubly robust. Simulations demonstrate the relevance of the theory in finite samples. Copyright 2005, Oxford University Press.

Simultaneous Determination of Dopamine, Serotonin and Ascorbic Acid at a Glassy Carbon Electrode Modified with Carbon-Spheres

A novel glassy carbon electrode (GCE) modified with carbon-spheres has been fabricated through a simple casting procedure. The modified GCE displays high selectivity and excellent electrochemical catalytic activities towards dopamine (DA), serotonin (5-HT), and ascorbic acid (AA). In the co-existence system, the peak separations between AA and DA, DA and 5-HT, and AA and 5-HT are large up to 230, 180, and 410 mV, respectively. Differential pulse voltammetry (DPV) has been employed to simultaneously detect DA, 5-HT, and AA, and the linear calibration curves for DA, 5-HT, and AA are obtained in the range of 20.0–150.0 μM, 40.0–750.0 μM and 300.0–2,000.0 μM with detection limits (S/N = 3) of 2.0 μM, 0.7 μM and 0.6 μM, respectively. The proposed electrode has been applied to detect DA, 5-HT, and AA in real samples using standard addition method with satisfactory results

Interface-induced spiral magnetic structure of epitaxial Fe films on GaAs(001)

We investigated the magnetic structure in epitaxial Fe films on GaAs(001) by taking advantage of planar Hall effect combining with static and dynamic magnetization measurements. The depth dependence of the magnetic structure was evidenced as a result of competition between in-plane interfacial uniaxial and bulk cubic magnetic anisotropies. The competing results exposed by these techniques allow us to image a spiral magnetic structure nearby the interface of the Fe/GaAs(001) system. This work provides an insight for electrical and magnetic properties in an ultrathin hybrid ferromagnet/non-magnet system

Edmond-Joseph Massicotte : Dessinateur de presse et caricaturiste

With the aim of utilizing O-2 as an oxidant, cascade reaction strategy was usually employed by first transforming O-2 into the in situ generated hydroperoxide and then oxidized the substrate. To combine the two steps more efficiently to get a higher reaction rate, a series of core-shell catalysts with core and shell having different wettabilities were designed. The catalysts were characterized by transmission electron microscopy, UV-vis spectroscopy, Fourier transform infrared, sessile water contact angle, among other methods. These catalysts were applied in the research of the diphenyl sulfide oxidation by the in situ generated hydroperoxide derived from ethylbenzene oxidation. Through control experiments, the hydrophobic modification in the shell and core will influence different steps of the overall cascade reaction. Further insight into the reaction illustrated that the overall reaction rate was not simply an adduct of the promotion effects from the two steps, which was mainly attributed to the inhibition effect for the co-oxidation of ethylbenzene with diphenyl sulfide. Through the guidance of the relationship, a rationally designed core shell catalyst with appropriate modifying organic groups showed an enhanced performance of the overall cascade reaction. The rational design of the catalysts would provide a reference for other cascade reactions

Effective Utilization of in Situ Generated Hydroperoxide by a Co-SiO2@Ti-Si Core-Shell Catalyst in the Oxidation Reactions

A core shell catalyst (Co-SiO2@Ti Si) with cobalt-based SiO2 nanocomposite (Co-SiO2) as the core and Ti-doped mesoporous silica as the shell was designed to catalyze a one-pot reaction of sulfide oxidation with in situ generated hydroperoxide. The catalyst was characterized by SEM, TEM, UV-vis spectroscopy, and XPS, among other methods. Compared to Co-SiO2 and the physical mixture of the two components (Co-SiO2 + Ti-Si), the core shell catalyst significantly enhanced the reaction rate of the sulfide oxidation. The utilization efficiency of the hydroperoxide was an important factor responsible for the differences in the reaction rates. A further mechanism study showed that the improvement of the efficiency was due to the existence of a coordination pathway. The core-shell structure of a bifunctional catalyst represents a strategy for improving the utilization efficiency of hydroperoxide