Genetic Factors Related to the Incidence of Type II Diabetes in Adults

As the seventh leading cause of death in the United States, diabetes affects 29.1 million people. In May, 2015 the U.S. CDC reported, the estimated total financial burden for diabetes in the United States at greater than $245 billion ($69 billion attributed to disability, lost days at work and premature death). The purpose of this study was to investigate genetic variances in parallel with type II diabetes. Through a five year prior search of Cochrane, Medline and Pubmed this review of the literature examined studies regarding type II diabetes related genetic variances specific to non-ethnic and ethnic populations of otherwise healthy adults aged 18-65 years old. Methods encompassed extracting DNA from nuclear pellets. Further genotyping was conducted using SNPlex or Assays on Demand. A p value of less than 0.05 was considered statistically significant. Literature reviews utilized centre-stratified analyses, combining evidence from each centre using fixed-effect meta-analyses. The authors then assessed research subjects against controls utilizing measured genotype and additive genetic models adjusted for age and gender. Significance thresholds were then adjusted where a p value of \u3c 0.05 was considered statistically significant. Franceschini et al. (2013), Wu et al. (2014) Hanson et al. (2013), Kato (2013), Yagootak and Frayling (2013), Sun, Yu and Hu (2014) and Pal and McCarthy (2013) stated over 60 genetic loci have been identified to date in candidate gene and genome-wide association studies regarding type II diabetes. Of the genetic loci discovered, Wu et al. (2014) and Yagatook and Frayling (2013) determined variants at TCF7L2 resemble the most robust correlation with type II diabetes. Wu et al. (2014) found a 96% concordance rate among monozygotic twins with type II diabetes, as well as a 40% incidence rate of developing type II diabetes among those who have first-degree relatives with the disease. However, Kato (2013) suggests previous studies only account for 5-10% of heritability associated with type II diabetes. Sun, Yu and Hu (2014) reported the concept of pharmacogenomics (drug molecular mechanisms related to gene variants and drug efficacy) may eventually drive clinical decision making regarding type II diabetes drug selection, dose titration and adverse side effect avoidance. Based on the results of the studies in this review, accurate genetic data reveals potential to evolve clinically into a valuable instrument, thereby facilitating optimized therapeutics and deferring or suspending the onset of type II diabetes.https://commons.und.edu/pas-grad-posters/1061/thumbnail.jp

RNA-Seq optimization with eQTL gold standards.

BackgroundRNA-Sequencing (RNA-Seq) experiments have been optimized for library preparation, mapping, and gene expression estimation. These methods, however, have revealed weaknesses in the next stages of analysis of differential expression, with results sensitive to systematic sample stratification or, in more extreme cases, to outliers. Further, a method to assess normalization and adjustment measures imposed on the data is lacking.ResultsTo address these issues, we utilize previously published eQTLs as a novel gold standard at the center of a framework that integrates DNA genotypes and RNA-Seq data to optimize analysis and aid in the understanding of genetic variation and gene expression. After detecting sample contamination and sequencing outliers in RNA-Seq data, a set of previously published brain eQTLs was used to determine if sample outlier removal was appropriate. Improved replication of known eQTLs supported removal of these samples in downstream analyses. eQTL replication was further employed to assess normalization methods, covariate inclusion, and gene annotation. This method was validated in an independent RNA-Seq blood data set from the GTEx project and a tissue-appropriate set of eQTLs. eQTL replication in both data sets highlights the necessity of accounting for unknown covariates in RNA-Seq data analysis.ConclusionAs each RNA-Seq experiment is unique with its own experiment-specific limitations, we offer an easily-implementable method that uses the replication of known eQTLs to guide each step in one's data analysis pipeline. In the two data sets presented herein, we highlight not only the necessity of careful outlier detection but also the need to account for unknown covariates in RNA-Seq experiments

Stellarator Optimization with Poloidal Field Coils

Stellarators are devices that use magnetic fields to optimize the conditions needed for plasmas to undergo fusion. Unlike tokamaks, stellarators do not rely on a plasma current but can produce a helical magnetic field using only external coils. In a stellarator, the coils surrounding the plasma are called modular coils and those that follow the plasma are called poloidal field coils. Modular coils can be difficult to build if they are too complex. An effort is underway to develop coil conditions that meet both physics and engineering constraints. The FOCUS code was developed to flexibly optimize stellarator coil configurations [C. Zhu, et al., Plasma Phys. Contr. Fusion 60, 065008 (2018)]. In this work, we will use the FOCUS code to develop and analyze coil configurations for a plasma boundary that is optimized for particle confinement. We will examine modular coil configurations with and without a set of poloidal field coils

Enrichment Map: A Network-Based Method for Gene-Set Enrichment Visualization and Interpretation

Gene-set enrichment analysis is a useful technique to help functionally characterize large gene lists, such as the results of gene expression experiments. This technique finds functionally coherent gene-sets, such as pathways, that are statistically over-represented in a given gene list. Ideally, the number of resulting sets is smaller than the number of genes in the list, thus simplifying interpretation. However, the increasing number and redundancy of gene-sets used by many current enrichment analysis software works against this ideal.To overcome gene-set redundancy and help in the interpretation of large gene lists, we developed “Enrichment Map”, a network-based visualization method for gene-set enrichment results. Gene-sets are organized in a network, where each set is a node and edges represent gene overlap between sets. Automated network layout groups related gene-sets into network clusters, enabling the user to quickly identify the major enriched functional themes and more easily interpret the enrichment results.)

Genetic and hypoxic alterations of the microRNA-210-ISCU1/2 axis promote iron-sulfur deficiency and pulmonary hypertension

Iron–sulfur (Fe‐S) clusters are essential for mitochondrial metabolism, but their regulation in pulmonary hypertension (PH) remains enigmatic. We demonstrate that alterations of the miR‐210‐ISCU1/2 axis cause Fe‐S deficiencies in vivo and promote PH. In pulmonary vascular cells and particularly endothelium, hypoxic induction of miR‐210 and repression of the miR‐210 targets ISCU1/2 down‐regulated Fe‐S levels. In mouse and human vascular and endothelial tissue affected by PH, miR‐210 was elevated accompanied by decreased ISCU1/2 and Fe‐S integrity. In mice, miR‐210 repressed ISCU1/2 and promoted PH. Mice deficient in miR‐210, via genetic/pharmacologic means or via an endothelial‐specific manner, displayed increased ISCU1/2 and were resistant to Fe‐S‐dependent pathophenotypes and PH. Similar to hypoxia or miR‐210 overexpression, ISCU1/2 knockdown also promoted PH. Finally, cardiopulmonary exercise testing of a woman with homozygous ISCU mutations revealed exercise‐induced pulmonary vascular dysfunction. Thus, driven by acquired (hypoxia) or genetic causes, the miR‐210‐ISCU1/2 regulatory axis is a pathogenic lynchpin causing Fe‐S deficiency and PH. These findings carry broad translational implications for defining the metabolic origins of PH and potentially other metabolic diseases sharing similar underpinnings.National Institutes of Health (U.S.) (U54‐CA151884)National Institutes of Health (U.S.) (R01‐DE016516‐06)National Institutes of Health (U.S.) (EB000244

Treatment sensitivity in the measurement of psychological flexibility

Psychological flexibility (PF) is a central construct in Acceptance and Commitment Therapy (ACT). Many studies have operationalized PF using the self-report Acceptance and Actions Questionnaire (AAQ-II). Information on the treatment sensitivity of self-report assessments of PF is lacking, however. We investigated differences in the treatment sensitivity of the AAQ-II compared to other measures of PF across various samples. Using three different clinical samples (N=164), we compared the pretreatment–posttreatment change scores of the AAQ-II to those of three alternative self-report questionnaires measuring PF in a within-subject design. Sensitivity to change was assessed with effect sizes and Reliable Change Index (RC). Without exception, effect sizes and rates of clinically significant change were larger in all three alternative questionnaires and across three populations compared to the standard formulation of the AAQ-II.The results of the present study show greater treatment sensitivity of three alternative questionnaires measuring PF compared to the AAQ-II. The results suggest that treatment effects concerning PF may have been underestimated depending on the wording and measure used. Implications for research on PF and ACT processes and outcomes are discussed

Diversity of Azoles Resistant Aspergillus Species Isolated from Experience and Naïve Soils in Nairobi County and Naivasha Sub-County Kenya

New triazole antifungals voriconazole, itraconazole and posaconazole are recommended for prophylaxis and treatment of both invasive and chronic fungal infections such as aspergillosis and aspergilloma. Emergence of azole-resistant among A. fumigatus isolates have been reported in other countries including Tanzania ascribed to either previous antifungal treatment, prophylaxis or triazoles use in agriculture. The use of azole based fungicides in the robust horticulture in Kenya is a significant risk factor for antifungal resistance. The study proposes to analyze environmental isolates of Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger for the presence of resistance against the triazoles antifungals. Fungicide naïve soils were obtained from uncultivated virgin fields while fungicide experience soils were collected from flower, agricultural and horticultural fields and greenhouses within Naivasha sub-county and Nairobi County. The fungal isolates were subjected to antifungal susceptibility to triazoles using broth micro dilution method. A total of 492 samples were analyzed in Nairobi, 52 isolates were identified and they resistance were as follow: A. fumigatus (32%), A. niger (26.09%), A. flavus (33.33%) and A .terreus (0%) and in Naivasha 44 isolates were isolated out of which 25 were A. fumigatus and its resistance was at 36%. Data were analyses using student T test and showed they no different between resistant and susceptible isolates from the two location. Data generated will serve to inform on the current status of triazoles resistance pattern and to raise concern emerging antifungal resistance in clinical practice

Enhanced Leak Detection

A key requirement for Veeder-Root’s Enhanced Leak Detection System is that it be able to test in situ for the presence of leaks at gasoline dispensing facilities. Aside from the obvious issues of safety and lost product, this functionality is obligatory for compliance with environmental standards mandated by federal and state oversight bodies, such as the California State Water Resources Control Board (SWRCB). The SWRCB demands a testing procedure that includes conditions as close to operational as possible, while still using environmentally safe gases as a test fluid. Although the test parameters (e.g., pressure) are allowed to deviate from operating conditions in order to facilitate the test procedure, a prescribed rescaling of the test thresholds must then be applied to account for the deviation. Whether the test is run at operation conditions or in a slightly different parameter regime, the fact that the testing must be done on the product and return lines after installation at a service station presents significant challenges in devising an effective test strategy