Decreased Expression of Cilia Genes in Pancreatic Islets as a Risk Factor for Type 2 Diabetes in Mice and Humans

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Complement Component C3 Is Highly Expressed in Human Pancreatic Islets and Prevents β Cell Death via ATG16L1 Interaction and Autophagy Regulation

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A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets

Close to 50 genetic loci have been associated with type 2 diabetes (T2D), but they explain only 15% of the heritability. In an attempt to identify additional T2D genes, we analyzed global gene expression in human islets from 63 donors. Using 48 genes located near T2D risk variants, we identified gene coexpression and protein-protein interaction networks that were strongly associated with islet insulin secretion and HbA(1c). We integrated our data to form a rank list of putative T2D genes, of which CHL1, LRFN2, RASGRP1, and PPM1K were validated in INS-1 cells to influence insulin secretion, whereas GPR120 affected apoptosis in islets. Expression variation of the top 20 genes explained 24% of the variance in HbA(1c) with no claim of the direction. The data present a global map of genes associated with islet dysfunction and demonstrate the value of systems genetics for the identification of genes potentially involved in T2D.     

Myosin degradation fragments in skeletal muscle

Myosin heavy chain degradation fragments produced in vivo have been identified in chicken pectoralis muscle. The fragments were identified by electrophoresis of unfractionated extracts of chicken pectoralis muscle on sodium dodecyl sulfate/polyacrylamide gels followed by immunoblotting on nitrocellulose sheets. Monoclonal antibodies directed against the S2 and light meromyosin subfragments as well as type II myosin-specific polyclonal antibodies directed against the entire myosin heavy chain were used to characterize the fragments, which range in molecular weight from approximately 80,000 to 180,000. All fragments contain the extreme carboxy-terminal portion of the molecule and are distinct from the classical proteolytic fragments such as heavy and light meromyosin, S1, S2 or rod. These fragments appear to be produced in vivo by proteolytic cleavage of peptides from the amino-terminal (S1) end of the heavy chain while the myosin molecule is still embedded in the thick filament. Fragment concentrations are estimated to be approximately 5 to 10% of that of the intact myosin heavy chain. These fragments are not the result of artifactual damage to myosin, e.g. proteolysis or hydrodynamic shear. The techniques described in this paper provide a probe into the early stages of myosin and thick filament degradation in vivo.     

Reaction of uracil with hypochlorous acid.

The end products of the reaction of uracil with at least a 10-fold excess of aqueous hypochlorous acid at pH 7–8 were found to be trichloroacetic acid, carbon dioxide and nitrogen trichloride. Little formation of trichloroacetic acid was observed after 24 hours when the ratio of hypochlorous acid to uracil was less than 4:1. An intermediate in the reaction was found to be 5-chlorouracil. This was also degraded by hypochlorous acid to trichloroacetic acid.     

Single Nucleotide Variants in KIF14 Gene May Have Prognostic Value in Breast Cancer

Molecular Diagnosis & Therapy - Human kinesin 14 (KIF14) is one of the 70 prognostic marker genes (so-called Amsterdam profile) previously identified by the microarray of breast carcinomas, and...