| 1. |
- Davegårdh, Cajsa, et al.
(författare)
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VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance and lower muscle quality (strength divided by mass) are hallmarks of type 2 diabetes (T2D). Here, we explore whether alterations in muscle stem cells (myoblasts) from individuals with T2D contribute to these phenotypes. We identify VPS39 as an important regulator of myoblast differentiation and muscle glucose uptake, and VPS39 is downregulated in myoblasts and myotubes from individuals with T2D. We discover a pathway connecting VPS39-deficiency in human myoblasts to impaired autophagy, abnormal epigenetic reprogramming, dysregulation of myogenic regulators, and perturbed differentiation. VPS39 knockdown in human myoblasts has profound effects on autophagic flux, insulin signaling, epigenetic enzymes, DNA methylation and expression of myogenic regulators, and gene sets related to the cell cycle, muscle structure and apoptosis. These data mimic what is observed in myoblasts from individuals with T2D. Furthermore, the muscle of Vps39(+/-) mice display reduced glucose uptake and altered expression of genes regulating autophagy, epigenetic programming, and myogenesis. Overall, VPS39-deficiency contributes to impaired muscle differentiation and reduced glucose uptake. VPS39 thereby offers a therapeutic target for T2D. Insulin resistance and lower muscle strength in relation to mass are hallmarks of type 2 diabetes. Here, the authors report alterations in muscle stem cells from individuals with type 2 diabetes that may contribute to these phenotypes through VPS39 mediated effects on autophagy and epigenetics.
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| 2. |
- Agui, A., et al.
(författare)
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Direct observation of interface effects of thin AlAs(100) layers buried in GaAs
- 2000
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Ingår i: Applied Surface Science. - : Elsevier. - 0169-4332 .- 1873-5584. ; 166:1-4, s. 309-312
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Tidskriftsartikel (refereegranskat)abstract
- A study of the electronic structure of ultrathin AlAs layers buried in GaAs(100) and their interfaces is presented. Al L2,3 soft-X-ray-emission (SXE) spectra from the AlAs layers were measured. The spectra show distinct thickness-dependent features, which are reproduced using ab initio calculations.
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| 3. |
- Ekström, Anette C., 1958-, et al.
(författare)
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Nurses challenges to support hospitalized patients regarding sexual-health issues
- 2016
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Ingår i: Journal of Nursing & Care. - : OMICS Publishing Group. - 2167-1168. ; 5:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: The approach to nursing should be characterized by a holistic view of the human being which includes sexual health. From a nursing perspective, it is therefore of most importance to have a dialogue about factors associated with sexual health also among hospitalized patients. However, to our knowledge there is a lack of qualitative studies regarding nurses attitudes about dialogue with patients about sexual health.Objective: To investigate nurses attitudes towards dialogue with hospitalized patients about sexual health.Methods: A qualitative method was used and interviews were conducted which then were analyzed using a qualitative content analysis. Eleven registered nurses were included, the inclusion criteria was: at least one year of experience as a nurse and working on a medical or surgical ward in a hospital in the southwest of Sweden. The participants were in the ages 25-65 and had worked as nurses between 2 and 30 years. Nine of the participants were women. The data were collected during 2011.Results: The nurses experiences of and reflections on dialogue with patients about sexual health were presented as a single main theme: Nurses challenges to support hospitalized patients with sexual health issues. This theme had three categories: Feeling uncomfortable, Feeling inadequate and Task-oriented care with related subcategories respectively.Conclusions: Nurses attitudes towards their dialogues about sexual health with hospitalized patients were less challenging if they were initiated by the patients or if the patients were men with medical causes related to sexual health. Lack of knowledge and support from colleagues became reasons why nurses felt inadequate about discussing sexual health with their patients.
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| 4. |
- Mankefors, S., et al.
(författare)
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Theoretical investigation of the thickness dependence of soft-x-ray emission from thin AlAs(100) layers buried in GaAs
- 2000
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Ingår i: Physical Review B Condensed Matter. - : American Physical Society. - 0163-1829 .- 1095-3795. ; 61:8, s. 5540-5545
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Tidskriftsartikel (refereegranskat)abstract
- Ultrathin AlAs(100) layers of 1-, 2-, and 5-ML thickness buried in GaAs are investigated by ab initio calculations. Unique experimental soft-x-ray emission spectra are explained in terms of interface effects and changes with layer thickness are found in the density of states. Only the central layer in the 5-ML geometry is bulklike. A valence-band offset of 0.53 eV is also found for this structure, while no offset exists in the 1- and 2-ML cases. Very good agreement is achieved between theory and experiment.
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| 5. |
- Rana, Rakesh, et al.
(författare)
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Selecting software reliability growth models and improving their predictive accuracy using historical projects data
- 2014
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Ingår i: Journal of Systems and Software. - : Elsevier BV. - 0164-1212 .- 1873-1228. ; 98, s. 59-78
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Tidskriftsartikel (refereegranskat)abstract
- During software development two important decisions organizations have to make are: how to allocate testing resources optimally and when the software is ready for release. SRGMs (software reliability growth models) provide empirical basis for evaluating and predicting reliability of software systems. When using SRGMs for the purpose of optimizing testing resource allocation, the model's ability to accurately predict the expected defect inflow profile is useful. For assessing release readiness, the asymptote accuracy is the most important attribute. Although more than hundred models for software reliability have been proposed and evaluated over time, there exists no clear guide on which models should be used for a given software development process or for a given industrial domain. Using defect inflow profiles from large software projects from Ericsson, Volvo Car Corporation and Saab, we evaluate commonly used SRGMs for their ability to provide empirical basis for making these decisions. We also demonstrate that using defect intensity growth rate from earlier projects increases the accuracy of the predictions. Our results show that Logistic and Gompertz models are the most accurate models; we further observe that classifying a given project based on its expected shape of defect inflow help to select the most appropriate model. (C) 2014 Elsevier Inc. All rights reserved.
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| 6. |
- Synnergren, Jane, 1967, et al.
(författare)
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Cardiomyogenic gene expression profiling of differentiating human embryonic stem cells.
- 2008
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Ingår i: Journal of biotechnology. - : Elsevier BV. - 0168-1656 .- 1873-4863. ; 134:1-2, s. 162-70
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Tidskriftsartikel (refereegranskat)abstract
- Human embryonic stem cells (hESCs) can differentiate into a variety of specialized cell types. Thus, they provide a model system for embryonic development to investigate the molecular processes of cell differentiation and lineage commitment. The development of the cardiac lineage is easily detected in mixed cultures by the appearance of spontaneously contracting areas of cells. We performed gene expression profiling of undifferentiated and differentiating hESCs and monitored 468 genes expressed during cardiac development and/or in cardiac tissue. Their transcription during early differentiation of hESCs through embryoid bodies (EBs) was investigated and compared with spontaneously differentiating hESCs maintained on feeders in culture without passaging (high-density (HD) protocol). We observed a larger variation in the gene expression between cells from a single cell line that were differentiated using two different protocols than in cells from different cell lines that were cultured according to the same protocol. Notably, the EB protocol resulted in more reproducible transcription profiles than the HD protocol. The results presented here provide new information about gene regulation during early differentiation of hESCs with emphasis on the cardiomyogenic program. In addition, we also identified regulatory elements that could prove critical for the development of the cardiomyocyte lineage.
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| 7. |
- Synnergren, Jane, 1967, et al.
(författare)
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Differentiating human embryonic stem cells express a unique housekeeping gene signature.
- 2007
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Ingår i: Stem cells (Dayton, Ohio). - : Oxford University Press (OUP). - 1066-5099 .- 1549-4918. ; 25:2, s. 473-80
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Tidskriftsartikel (refereegranskat)abstract
- Housekeeping genes (HKGs) are involved in basic functions needed for the sustenance of the cell and are assumed to be constitutively expressed at a constant level. Based on these features, HKGs are frequently used for normalization of gene expression data. In the present study, we used the CodeLink Gene Expression Bioarray system to interrogate changes in gene expression occurring during differentiation of human ESCs (hESCs). Notably, in the three hESC lines used for the study, we observed that the RNA levels of 56 frequently used HKGs varied to a degree that rendered them inappropriate as reference genes. Therefore, we defined a novel set of HKGs specifically for hESCs. Here we present a comprehensive list of 292 genes that are stably expressed (coefficient of variation <20%) in differentiating hESCs. These genes were further grouped into high-, medium-, and low-expressed genes. The expression patterns of these novel HKGs show very little overlap with results obtained from somatic cells and tissues. We further explored the stability of this novel set of HKGs in independent, publicly available gene expression data from hESCs and observed substantial similarities with our results. Gene expression was confirmed by real-time quantitative polymerase chain reaction analysis. Taken together, these results suggest that differentiating hESCs have a unique HKG signature and underscore the necessity to validate the expression profiles of putative HKGs. In addition, this novel set of HKGs can preferentially be used as controls in gene expression analyses of differentiating hESCs.
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| 8. |
- Synnergren, Jane, et al.
(författare)
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Differentiating human embryonic stem cells express a unique housekeeping gene signature
- 2006
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Ingår i: 4th ISSCR Annual Meeting.
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Konferensbidrag (refereegranskat)abstract
- Human embryonic stem cells (hESCs) represent populations of pluripotent undifferentiated cells with unlimited replication capacity which can be coaxed to differentiate into a variety of specialized cells. As a result, there is great hope that hESCs will be extremely useful by providing platforms for various in vitro applications (e.g. in drug discovery) as well as for future use of hESCs and their differentiated progeny in cell replacement therapies. In order to realize the potential of hESCs, it is necessary to gain much deeper knowledge about the processes that govern differentiation of these cells.In recent years, significant progress towards understanding cellular differentiation has been fuelled, in part, by studying gene expression using microarrays. In this large scale studies, statistical methods are used to normalize the gene expression data and render comparisons between different samples. In lower throughput analyses, RNA levels in hESCs are also measured using RT-PCR requiring normalization of the gene expression data to adequately correct for inter-sample variation. In general, investigators have used the traditional housekeeping genes (HKGs) (e.g. GAPDH, b-tubulin, b-actin) in studies of hESCs. HKGs are involved in basic functions needed for the sustenance of the cell and are assumed to be constitutively expressed at a constant level. Based on these features, HKGs are frequently used for normalization of gene expression data. However, it is well known that the expression of several of these genes vary considerably in adult tissues and their suitability as HKGs in hESCs remains to be proven. In this regard, the RNA levels of HPRT and b-tubulin were shown to vary substantially in differentiating mouse ESCs.In the present study, we used the CodeLinkTM Gene Expression Bioarray system to interrogate changes in gene expression occurring during differentiation of hESCs. Notably, in the three hESC lines used for the study, we observed that the RNA levels of 56 frequently used HKGs varied to a degree that rendered them inappropriate as reference genes. Therefore, we defined a novel set of HKGs specifically for hESCs. Here we present a comprehensive list of 292 genes that are stably expressed (coefficient of variation<20%) in differentiating hESCs. These genes were further grouped into high, medium, and low expressed genes. The expression patterns of these novel HKGs show very little overlap with results obtained from somatic cells and tissues. We further explored the stability of this novel set of HKGs in independent, publicly available gene expression data from hESCs and observed substantial similarities in terms of stably expressed genes. Taken together, these results suggest that hESCs have a unique HKG signature and underscore the necessity to validate the expression profiles of putative HKGs. In addition, the novel set of identified HKGs can preferentially be used as controls in gene expression analyses of differentiating hESCs.
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