• Reduced Serum Vitamin Dâ Binding Protein Levels Are Associated With Type 1 Diabetes

      Blanton, Dustin; Han, Zhao; Bierschenk, Lindsey; Linga-Reddy, M.V. Prasad; Wang, Hongjie; Clare-Salzler, Michael; Haller, Michael; Schatz, Desmond; Myhr, Courtney; She, Jin-Xiong; et al. (2011-10-16)
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    • The Role of Endoplasmic Reticulum Stress in Autoimmune-Mediated Beta-Cell Destruction in Type 1 Diabetes

      Zhong, Jixin; Rao, Xiaoquan; Xu, Jun-Fa; Yang, Ping; Wang, Cong-Yi; Center for Biotechnology and Genomic Medicine (2012-02-14)
      Unlike type 2 diabetes which is caused by the loss of insulin sensitivity, type 1 diabetes (T1D) is manifested by the absolute deficiency of insulin secretion due to the loss of β mass by autoimmune response against β-cell self-antigens. Although significant advancement has been made in understanding the pathoetiology for type 1 diabetes, the exact mechanisms underlying autoimmune-mediated β-cell destruction, however, are yet to be fully addressed. Accumulated evidence demonstrates that endoplasmic reticulum (ER) stress plays an essential role in autoimmune-mediated β-cell destruction. There is also evidence supporting that ER stress regulates the functionality of immune cells relevant to autoimmune progression during T1D development. In this paper, we intend to address the role of ER stress in autoimmune-mediated β-cell destruction during the course of type 1 diabetes. The potential implication of ER stress in modulating autoimmune response will be also discussed. We will further dissect the possible pathways implicated in the induction of ER stress and summarize the potential mechanisms underlying ER stress for mediation of β-cell destruction. A better understanding of the role for ER stress in T1D pathoetiology would have great potential aimed at developing effective therapeutic approaches for the prevention/intervention of this devastating disorder.
    • A statistical framework for integrating two microarray data sets in differential expression analysis.

      Lai, Yinglei; Eckenrode, Sarah E; She, Jin-Xiong; Center for Biotechnology and Genomic Medicine (2009-02-11)
      BACKGROUND: Different microarray data sets can be collected for studying the same or similar diseases. We expect to achieve a more efficient analysis of differential expression if an efficient statistical method can be developed for integrating different microarray data sets. Although many statistical methods have been proposed for data integration, the genome-wide concordance of different data sets has not been well considered in the analysis. RESULTS: Before considering data integration, it is necessary to evaluate the genome-wide concordance so that misleading results can be avoided. Based on the test results, different subsequent actions are suggested. The evaluation of genome-wide concordance and the data integration can be achieved based on the normal distribution based mixture models. CONCLUSION: The results from our simulation study suggest that misleading results can be generated if the genome-wide concordance issue is not appropriately considered. Our method provides a rigorous parametric solution. The results also show that our method is robust to certain model misspecification and is practically useful for the integrative analysis of differential expression.
    • TRPM8 mechanism of autonomic nerve response to cold in respiratory airway.

      Xing, Hong; Ling, Jennifer X; Chen, Meng; Johnson, Richard D; Tominaga, Makoto; Wang, Cong-Yi; Gu, Jianguo; Center for Biotechnology and Genomic Medicine (2008-06-18)
      Breathing cold air without proper temperature exchange can induce strong respiratory autonomic responses including cough, airway constriction and mucosal secretion, and can exacerbate existing asthma conditions and even directly trigger an asthma attack. Vagal afferent fiber is thought to be involved in the cold-induced respiratory responses through autonomic nerve reflex. However, molecular mechanisms by which vagal afferent fibers are excited by cold remain unknown. Using retrograde labeling, immunostaining, calcium imaging, and electrophysiological recordings, here we show that a subpopulation of airway vagal afferent nerves express TRPM8 receptors and that activation of TRPM8 receptors by cold excites these airway autonomic nerves. Thus activation of TRPM8 receptors may provoke autonomic nerve reflex to increase airway resistance. This putative autonomic response may be associated with cold-induced exacerbation of asthma and other pulmonary disorders, making TRPM8 receptors a possible target for prevention of cold-associated respiratory disorders.