| 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. |
- Lindgren, David, et al.
(författare)
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Isolation and characterization of progenitor-like cells from human renal proximal tubules.
- 2011
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 178:2, s. 828-837
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Tidskriftsartikel (refereegranskat)abstract
- The tubules of the kidney display a remarkable capacity for self-renewal on damage. Whether this regeneration is mediated by dedifferentiating surviving cells or, as recently suggested, by stem cells has not been unequivocally settled. Herein, we demonstrate that aldehyde dehydrogenase (ALDH) activity may be used for isolation of cells with progenitor characteristics from adult human renal cortical tissue. Gene expression profiling of the isolated ALDH(high) and ALDH(low) cell fractions followed by immunohistochemical interrogation of renal tissues enabled us to delineate a tentative progenitor cell population scattered through the proximal tubules (PTs). These cells expressed CD24 and CD133, previously described markers for renal progenitors of Bowman's capsule. Furthermore, we show that the PT cells, and the glomerular progenitors, are positive for KRT7, KRT19, BCL2, and vimentin. In addition, tubular epithelium regenerating on acute tubular necrosis displayed long stretches of CD133(+)/VIM(+) cells, further substantiating that these cells may represent a progenitor cell population. Furthermore, a potential association of these progenitor cells with papillary renal cell carcinoma was discovered. Taken together, our data demonstrate the presence of a previously unappreciated subset of the PT cells that may be endowed with a more robust phenotype, allowing increased resistance to acute renal injury, enabling rapid repopulation of the tubules.
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| 3. |
- 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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| 4. |
- Sherwood, Victoria, et al.
(författare)
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WNT5A-mediated β-catenin-independent signalling is a novel regulator of cancer cell metabolism.
- 2014
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 35:4, s. 784-794
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Tidskriftsartikel (refereegranskat)abstract
- WNT5A has been identified as an important ligand in the malignant progression of a number of tumours. Although WNT5A signalling is often altered in cancer, the ligand's role as either a tumour suppressor or oncogene varies between tumour types and is a contemporary issue for investigators of β-catenin-independent WNT signalling in oncology. Here, we report that one of the initial effects of active WNT5A signalling in malignant melanoma cells is an alteration in cellular energy metabolism and specifically an increase in aerobic glycolysis. This was found to be at least in part due to an increase in active Akt signalling and lactate dehydrogenase (LDH) activity. The clinical relevance of these findings was strengthened by a strong correlation (P < 0.001) between the expression of WNT5A and LDH isoform V in a cohort of melanocytic neoplasms. We also found effects of WNT5A on energy metabolism in breast cancer cells, but rather than promoting aerobic glycolysis as it does in melanoma, WNT5A signalling increased oxidative phosphorylation rates in breast cancer cells. These findings support a new role for WNT5A in the metabolic reprogramming of cancer cells that is a context- dependent event.
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| 5. |
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| 6. |
- Sjöberg, Karin, et al.
(författare)
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Nationell Miljöövervakning - LuftData t.o.m. 2009
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- På uppdrag av Naturvårdsverkets Miljöövervakningsenhet bedrivs mätningar av luftens och nederbördens sammansättning, främst i bakgrundsmiljö, inom olika mätprogram. IVL Svenska Miljöinstitutet har ansvar för genomförandet av merparten av verksamheten inom luftområdet. Därtill ombesörjer både Institutionen för Tillämpad Miljöteknik (ITM) vid Stockholms universitet och Institutionen för Mark och Miljö vid Sveriges lantbruksuniversitet (SLU) delar av övervakningen. De samlade resultaten från mätningarna till och med 2009 redovisas i denna rapport. Det har generellt sett skett en avsevärd förbättring avseende såväl halter i luft som deposition i bakgrundsmiljö för flertalet av de luftföroreningskomponenter som övervakas inom den nationella miljöövervakningen sedan mätningarna startade för mellan 10 och 30 år sedan. Utvecklingen har dock varierat i något olika utsträckning beroende på komponent och lokalisering i landet. Föroreningsbelastningen är oftast lägre ju längre norrut man kommer. För de flesta de ämnen som det finns miljökvalitetsnormer (MKN) respektive miljömål för ligger halterna avsevärt lägre än angivna gräns- och målvärden. Halterna av ozon överskrider i dagsläget MKN för hälsa. För såväl ozon som bensen (i urban bakgrund) och eten finns risk för haltnivåer som överstiger miljömålen.
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| 7. |
- Säll-Hansson, Karin, et al.
(författare)
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The meaning of the experiences of persons with chronic pain in their encounters with the health service
- 2011
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Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; 25:3, s. 444-450
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Tidskriftsartikel (refereegranskat)abstract
- The meaning of the experiences of persons with chronic pain in their encounters with the health service Chronic pain causes great suffering for those affected and treating it is one of the most common assignments in the health service. The aim of the study was to investigate the meaning of the experiences of persons with chronic pain in their encounters with health service staff. The study had a descriptive design with a phenomenological approach based on the perspective of caring science. Interviews were carried out with eight patients. The study showed that patients experienced a positive approach and that the staff had understood the serious nature of the situation. A positive approach can communicate hope and help to strengthen the patient. It is important to ask the patient about how he/she experiences his/her situation and thus gain an insight into this person's lifeworld. Participation entailed being active oneself and calling attention to one's needs and wishes for treatment. The study also showed that a negative approach by the staff played a prominent part in their experiences and appeared to be engraved in their memories. A negative approach is felt as being insulting and belittling. Patients with chronic pain felt that they were discredited and that their experience of their situation was called into question. They had to fight to get care and had to suggest treatments and examinations. There were also patients who had neither been asked about their pain experience nor had the opportunity to assess their pain with an assessment scale. Some of the phases in Travelbee's relationship model could be seen in several of the encounters but not all. The participants did not always feel that the manner of the nursing staff was empathetic or sympathetic, which led to greater suffering.
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| 8. |
- Annertz, Karin, et al.
(författare)
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High-risk HPV and survival in patients with oral and oropharyngeal squamous cell carcinoma : 5-year follow up of a population-based study
- 2014
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Ingår i: Acta Oto-Laryngologica. - : Informa Healthcare. - 0001-6489 .- 1651-2251. ; 8:134, s. 843-851
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Tidskriftsartikel (refereegranskat)abstract
- CONCLUSION: No statistically significant 5-year survival difference was seen in patients with oral and oropharyngeal squamous cell carcinoma (OOPSCC) between high-risk HPV-positive and -negative groups in this population-based study. OBJECTIVES: To see if the formerly observed higher risk for recurrence or second primary tumour (SPT) in high-risk HPV-positive patients with OOPSCC corresponds to worse survival. METHODS: A total of 128 consecutive, previously untreated patients with OOPSCC, who were part of a population-based case-control study in southern Sweden during 2000-2004, were included. A mouthwash sample was collected and exfoliated cells were collected with cotton-tipped swabs from the tonsillar fossa and the tumour. Specimens were analysed for HPV DNA using nested polymerase chain reaction (PCR). Disease-specific survival (DSS) and DSS difference between HPV-negative and HPV-positive patients were calculated. The relationship between age, stage, high-risk HPV status and DSS was assessed. Oral and oropharyngeal tumours were assessed separately. RESULTS: Mean DSS in months was 80.7/68.6 (high-risk HPV-negative/high-risk HPV-positive) for oral cavity tumours (p = 0.18) and 67.6/78.3 (high-risk HPV-negative/high-risk HPV-positive) for oropharyngeal tumours (p = 0.47). For oral cavity tumours, age, T status, N status and stage all showed significant differences in DSS. For oropharyngeal tumours, no significant difference regarding DSS was found.
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| 9. |
- 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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| 10. |
- Baard, Patrik, 1981-
(författare)
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Sustainable Goals : Feasible Paths to Desirable Long-Term Futures
- 2014
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The general aim of this licentiate thesis is to analyze the framework in which long-term goals are set and subsequently achieved. It is often claimed that goals should be realistic, meaning that they should be adjusted to known abilities. This thesis will argue that this might be very difficult in areas related to sustainable development and climate change adaptation, and that goals that are, to an acceptable degree, unrealistic, can have important functions.Essay I discusses long-term goal setting. When there is a great temporal discrepancy between the point in time of setting and achieving a goal, many uncertainties have to be considered. The surrounding world and the agent’s abilities and values might change. This is an ontological uncertainty. We often form beliefs regarding how abilities and values might change, but this belief is always uncertain. This is an epistemological uncertainty. A form of goal called cautiously utopian goals is proposed, which incorporate such uncertainties, but enables goal setting with long time-frames.Essay II discusses the issue of goals intended to reduce great risks. We cannot expect an agent to do something that lies beyond this agent’s abilities, as exemplified in the principle ‘ought implies can’. Adjusting goals to what we currently, with a high degree of certainty know could be done is difficult. If not including an estimation of how abilities can change, important performance-enhancing functions of goals might be lost. It is argued that very ambitious goals should be set. This is partly due to the great magnitude and likelihood of unwanted consequences and partly due to the difficulty of delineating what lies in agents’ capacity to manage complex risks.Essay III discusses a decision-facilitating tool Sustainability Analysis to be used by Swedish municipal planners. One sub-part of the tool, Goal Conflict Analysis, can be used to identify how the consequences of a planned adaptation measure will affect other long-term municipal goals. Identified goal conflicts can then be used in order to determine whether the conflicts are acceptable, or whether a different adaptation measure should be worked out. The paper discusses a workshop in a Swedish municipality in which the tool has been tested.
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