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1.
Nat Commun ; 8: 15652, 2017 06 06.
Article in English | MEDLINE | ID: mdl-28585545

ABSTRACT

Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion, but the mechanisms underlying insulin secretion failure are not completely understood. Here, we show that a set of co-expressed genes, which is enriched for genes with islet-selective open chromatin, is associated with T2D. These genes are perturbed in T2D and have a similar expression pattern to that of dedifferentiated islets. We identify Sox5 as a regulator of the module. Sox5 knockdown induces gene expression changes similar to those observed in T2D and diabetic animals and has profound effects on insulin secretion, including reduced depolarization-evoked Ca2+-influx and ß-cell exocytosis. SOX5 overexpression reverses the expression perturbations observed in a mouse model of T2D, increases the expression of key ß-cell genes and improves glucose-stimulated insulin secretion in human islets from donors with T2D. We suggest that human islets in T2D display changes reminiscent of dedifferentiation and highlight SOX5 as a regulator of ß-cell phenotype and function.


Subject(s)
Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/metabolism , Insulin-Secreting Cells/metabolism , SOXD Transcription Factors/metabolism , Animals , Calcium/metabolism , Calcium Channels/metabolism , Chromatin/metabolism , Exocytosis , Female , Gene Expression Regulation , Humans , Insulin/metabolism , Islets of Langerhans/metabolism , Male , Mice , Mice, Inbred C57BL , Oligonucleotide Array Sequence Analysis , Phenotype , Phlorhizin/chemistry , RNA, Small Interfering/metabolism , Rats , Valproic Acid/chemistry
2.
Cyberpsychol Behav ; 4(2): 279-86, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11710253

ABSTRACT

In this study we compared collaboration on a puzzle-solving task carried out by two persons in a virtual and a real environment. The task, putting together a cube consisting of different colored blocks in a "Rubiks" cube-type puzzle, was performed both in a shared virtual environment (VE) setting, using a Cave-type virtual reality (VR) system networked with a desktop VR system, and with cardboard colored blocks in an equivalent real setting. The aims of the study were to investigate presence, co-presence, collaboration, leadership, and performance in the two settings. We found that the participants contributed unequally to the task in the VE, and also found differences in collaboration between the virtual and the real setting.


Subject(s)
Form Perception , Problem Solving , User-Computer Interface , Humans , Internet
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