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- Borestrom, C., et al.
(författare)
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A CRISP(e)R view on kidney organoids allows generation of an induced pluripotent stem cell-derived kidney model for drug discovery
- 2018
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Ingår i: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 94:6, s. 1099-1110
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Tidskriftsartikel (refereegranskat)abstract
- Development of physiologically relevant cellular models with strong translatability to human pathophysiology is critical for identification and validation of novel therapeutic targets. Herein we describe a detailed protocol for generation of an advanced 3-dimensional kidney cellular model using induced pluripotent stem cells, where differentiation and maturation of kidney progenitors and podocytes can be monitored in live cells due to CRISPR/Cas9-mediated fluorescent tagging of kidney lineage markers (SIX2 and NPHS1). Utilizing these cell lines, we have refined the previously published procedures to generate a new, higher throughput protocol suitable for drug discovery. Using paraffin-embedded sectioning and whole-mount immunostaining, we demonstrated that organoids grown in suspension culture express key markers of kidney biology (WT1, ECAD, LTL, nephrin) and vasculature (CD31) within renal cortical structures with microvilli, tight junctions and podocyte foot processes visualized by electron microscopy. Additionally, the organoids resemble the adult kidney transcriptomics profile, thereby strengthening the translatability of our in vitro model. Thus, development of human nephron-like structures in vitro fills a major gap in our ability to assess the effect of potential treatment on key kidney structures, opening up a wide range of possibilities to improve clinical translation.
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- Söndergaard Hansen, Jesper, et al.
(författare)
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Perilipin 1 binds to aquaporin 7 in human adipocytes and controls its mobility via protein kinase A mediated phosphorylation
- 2016
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Ingår i: Metabolism-Clinical and Experimental. - : Elsevier BV. - 0026-0495. ; 65:12, s. 1731-1742
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence suggests that dysregulated glycerol metabolism contributes to the pathophysiology of obesity and type 2 diabetes. Glycerol efflux from adipocytes is regulated by the aquaglyceroporin AQP7, which is translocated upon hormone stimulation. Here, we propose a molecular mechanism where the AQP7 mobility in adipocytes is dependent on perilipin 1 and protein kinase A. Biochemical analyses combined with ex vivo studies in human primary adipocytes, demonstrate that perilipin 1 binds to AQP7, and that catecholamine activated protein kinase A phosphorylates the N-terminus of AQP7, thereby reducing complex formation. Together, these findings are indicative of how glycerol release is controlled in adipocytes, and may pave the way for the future design of drugs against human metabolic pathologies.
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- Fic, A, et al.
(författare)
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Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S.
- 2015
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Ingår i: Toxicology in Vitro. - : Elsevier BV. - 1879-3177 .- 0887-2333. ; 29:5, s. 1060-1069
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Tidskriftsartikel (refereegranskat)abstract
- The bisphenols AF (BPAF) and S (BPS) are structural analogs of the endocrine disruptor bisphenol A (BPA), and are used in common products as a replacement for BPA. To elucidate genome-wide gene expression responses, estrogen-dependent osteosarcoma cells were cultured with 10nM BPA, BPAF, or BPS, for 8h and 3months. Genome-wide gene expression was analyzed using the Illumina Expression BeadChip. Three months exposure had significant effects on gene expression, particularly for BPS, followed by BPAF and BPA, according to the number of differentially expressed genes (1980, 778, 60, respectively), the magnitude of changes in gene expression, and the number of enriched biological processes (800, 415, 33, respectively) and pathways (77, 52, 6, respectively). 'Embryonic skeletal system development' was the most enriched bone-related process, which was affected only by BPAF and BPS. Interestingly, all three bisphenols showed highest down-regulation of genes related to the cardiovascular system (e.g., NPPB, NPR3, TXNIP). BPA only and BPA/BPAF/BPS also affected genes related to the immune system and fetal development, respectively. For BPAF and BPS, the 'isoprenoid biosynthetic process' was enriched (up-regulated genes: HMGCS1, PDSS1, ACAT2, RCE1, DHDDS). Compared to BPA, BPAF and BPS had more effects on gene expression after long-term exposure. These findings stress the need for careful toxicological characterization of BPA analogs in the future.
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- McGrath, Cormac, et al.
(författare)
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Twelve tips for conducting qualitative research interviews.
- 2019
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Ingår i: Medical teacher. - 1466-187X .- 0142-159X. ; 41:9, s. 1002-1006
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Tidskriftsartikel (refereegranskat)abstract
- The qualitative research interview is an important data collection tool for a variety of methods used within the broad spectrum of medical education research. However, many medical teachers and life science researchers undergo a steep learning curve when they first encounter qualitative interviews, both in terms of new theory but also regarding new methods of inquiry and data collection. This article introduces the concept of qualitative research interviews for novice researchers within medical education, providing 12 tips for conducting qualitative research interviews.
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- Palmgren, Per J., et al.
(författare)
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A qualitative exploration of chiropractic and physiotherapy teachers' experiences and conceptualizations of the educational environment
- 2018
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Ingår i: Journal of Chiropractic Education. - 1042-5055 .- 2374-250X. ; 32:1, s. 10-22
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Tidskriftsartikel (refereegranskat)abstract
- Objective: There has been increasing scholarly interest in the role of environments in health care professional education, and the value of these has been widely acknowledged as an influential factor in educational quality. However, little is known about how teachers experience the environment, and there is a recognizable absence of a perspective from chiropractic and physiotherapy faculties. The aim of this study was to explore and contrast chiropractic and physiotherapy teachers' experiences and conceptualizations of the meaning of the educational environment. Methods: In this qualitative study, we performed semistructured interviews with 14 teachers, purposefully selected to obtain richness, variation, and breadth in the data. The data were analyzed using inductive qualitative content analysis. Results: The most noteworthy findings were, first, that chiropractic teachers experienced the meaning of the environment as motivating a vocational practice and modeling ideal, supporting and managing stressed students, and including students in the community of chiropractors. Physiotherapy teachers experienced the meaning of the environment as putting the pedagogical vision into practice, balancing students' expectations, and providing the prerequisites to grow within the profession. Second, both groups of teachers held common conceptualizations of the constituents of the environment as physical, organizational, relational, communicational, and pedagogical; however, they attached different connotations to these dimensions. Conclusion: The findings conveyed a variance in the experience of the meaning of the educational environment that can be attributed to contextual and cultural differences.
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