| 1. |
- Fadista, Joao, et al.
(författare)
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Global genomic and transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism.
- 2014
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 111:38, s. 13924-13929
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variation can modulate gene expression, and thereby phenotypic variation and susceptibility to complex diseases such as type 2 diabetes (T2D). Here we harnessed the potential of DNA and RNA sequencing in human pancreatic islets from 89 deceased donors to identify genes of potential importance in the pathogenesis of T2D. We present a catalog of genetic variants regulating gene expression (eQTL) and exon use (sQTL), including many long noncoding RNAs, which are enriched in known T2D-associated loci. Of 35 eQTL genes, whose expression differed between normoglycemic and hyperglycemic individuals, siRNA of tetraspanin 33 (TSPAN33), 5'-nucleotidase, ecto (NT5E), transmembrane emp24 protein transport domain containing 6 (TMED6), and p21 protein activated kinase 7 (PAK7) in INS1 cells resulted in reduced glucose-stimulated insulin secretion. In addition, we provide a genome-wide catalog of allelic expression imbalance, which is also enriched in known T2D-associated loci. Notably, allelic imbalance in paternally expressed gene 3 (PEG3) was associated with its promoter methylation and T2D status. Finally, RNA editing events were less common in islets than previously suggested in other tissues. Taken together, this study provides new insights into the complexity of gene regulation in human pancreatic islets and better understanding of how genetic variation can influence glucose metabolism.
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| 2. |
- Prokopenko, Inga, et al.
(författare)
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A Central Role for GRB10 in Regulation of Islet Function in Man.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Variants in the growth factor receptor-bound protein 10 (GRB10) gene were in a GWAS meta-analysis associated with reduced glucose-stimulated insulin secretion and increased risk of type 2 diabetes (T2D) if inherited from the father, but inexplicably reduced fasting glucose when inherited from the mother. GRB10 is a negative regulator of insulin signaling and imprinted in a parent-of-origin fashion in different tissues. GRB10 knock-down in human pancreatic islets showed reduced insulin and glucagon secretion, which together with changes in insulin sensitivity may explain the paradoxical reduction of glucose despite a decrease in insulin secretion. Together, these findings suggest that tissue-specific methylation and possibly imprinting of GRB10 can influence glucose metabolism and contribute to T2D pathogenesis. The data also emphasize the need in genetic studies to consider whether risk alleles are inherited from the mother or the father.
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| 3. |
- Anya, Obinna, et al.
(författare)
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The Morphing Organization : Rethinking Groupwork Systems in the Era of Crowdwork
- 2014
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Ingår i: Proceedings of the 18th International Conference on Supporting Group Work. - New York : Association for Computing Machinery (ACM). - 9781450330435 ; , s. 317-320
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Konferensbidrag (refereegranskat)abstract
- Web 2.0 has provided organizations remarkable opportunities to improve productivity, gain competitive advantage, and increase participation by engaging crowds to accomplish tasks at scale. However, establishing and integrating crowd-based systems into organizations is still an open question. The systems and the collaborative processes they enable appear diametrically in dissonance with the norms and culture of collaboration and knowledge sharing in traditional organizations. They require mechanisms for articulation of work, coordination, cooperation, and knowledge co-creation that are fundamentally different from those in current groupwork systems and processes. This workshop will bring together researchers investigating issues related to social computing and collaborative technologies, organizational science, crowdsourcing, and workplace research, work in industry, government and voluntary sectors, to discuss the future of groupwork systems in the era of crowdwork. Building on two workshops hosted at ACM CSCW 2014, we will explore questions such as: How does the shift in organizational work from a closed system with known individuals, to an open and crowd model that requires engagement with an undefined network of people, affect how we conceptualize groupwork? What are the implications for the design of groupwork systems? What can the crowdsourcing research community learn from groupwork systems, or conversely what can groupwork researchers learn from crowdsourcing? How do cultures, motivations, ownership and representation fit into these systems? The workshop will advance our understanding of this area, through presentations, discussion, and activities to articulate an agenda for future research.
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| 4. |
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| 5. |
- Mondlane, Avelino I., et al.
(författare)
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Insurance as Strategy for Flood Risk Management at Limpopo River Basin – A decision making Process under Uncertainty
- 2013
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Ingår i: International Journal of Computers & Technology. - : CIRWOLRD. - 2277-3061. ; 10:8, s. 1862-1877
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Tidskriftsartikel (refereegranskat)abstract
- The Limpopo River Basin, one of the nine international rivers crossing Mozambique, historically has shown to be cyclically flooded, undermining the economic and social development of its four riparian countries. Local and external added efforts are always in place when floods occur. Nowadays there are recommended ex-ante instruments to prevent floods and one of the most applicable instruments worldwide is insurance. Most of the inhabitants, even governments, affected by Limpopo River Basin are poor, therefore our concern regards the viability to apply insurance as a strategy for flood risk management. Moreover our research investigates to what extent the application of insurance, within two identified communities as case study, might create an added value in the process of decision making on flood risk management for Limpopo River Basin.
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