| 1. |
- Ali, Yusuf, et al.
(författare)
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The anterior chamber of the eye is a transplantation site that supports and enables visualisation of beta cell development in mice
- 2016
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 59:5, s. 1007-1011
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Tidskriftsartikel (refereegranskat)abstract
- In vivo imaging of the developing pancreas is challenging due to the inaccessibility of the tissue. To circumvent this, on embryonic day 10.5 (E10.5) we transplanted a mouse developing pancreatic bud into the anterior chamber of the eye (ACE) to determine whether the eye is a useful transplant site to support pancreas development. We transplanted an E10.5 dorsal pancreatic bud into the ACE of a syngeneic recipient mouse. Using a mouse insulin promoter-green fluorescent protein (MIP-GFP) mouse as the tissue donor, we non-invasively imaged the pancreatic bud as it develops at single beta cell resolution across time. The transplanted pancreatic bud rapidly engrafts and vascularises when transplanted into the ACE. The pancreatic progenitor cells differentiate into exocrine and endocrine cells, including cells expressing insulin, glucagon and somatostatin. The morphology of the transplanted pancreatic bud resembles that of the native developing pancreas. Beta cells within the transplanted pancreatic bud respond to glucose in a manner similar to that of native fetal beta cells and superior to that of in vitro developed beta cells. Unlike in vitro grown pancreatic explants, pancreatic tissue developing in the ACE is vascularised, providing the developing pancreatic tissue with a milieu resembling the native situation. Altogether, we show that the ACE is able to support growth, differentiation and function of a developing pancreatic bud across time in vivo.
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| 2. |
- Annicotte, Jean-Sébastien, et al.
(författare)
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Pancreatic-duodenal homeobox 1 regulates expression of liver receptor homolog 1 during pancreas development.
- 2003
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Ingår i: Molecular and Cellular Biology. - 0270-7306 .- 1098-5549. ; 23:19, s. 6713-6124
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Tidskriftsartikel (refereegranskat)abstract
- Liver receptor homolog 1 (LRH-1) and pancreatic-duodenal homeobox 1 (PDX-1) are coexpressed in the pancreas during mouse embryonic development. Analysis of the regulatory region of the human LRH-1 gene demonstrated the presence of three functional binding sites for PDX-1. Electrophoretic mobility shift assays and chromatin immunoprecipitation analysis showed that PDX-1 bound to the LRH-1 promoter, both in cultured cells in vitro and during pancreatic development in vivo. Retroviral expression of PDX-1 in pancreatic cells induced the transcription of LRH-1, whereas reduced PDX-1 levels by RNA interference attenuated its expression. Consistent with direct regulation of LRH-1 expression by PDX-1, PDX-1(-/-) mice expressed smaller amounts of LRH-1 mRNA in the embryonic pancreas. Taken together, our data indicate that PDX-1 controls LRH-1 expression and identify LRH-1 as a novel downstream target in the PDX-1 regulatory cascade governing pancreatic development, differentiation, and function.
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| 3. |
- Avall, Karin, et al.
(författare)
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Apolipoprotein CIII links islet insulin resistance to beta-cell failure in diabetes
- 2015
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:20, s. E2611-E2619
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance and beta-cell failure are the major defects in type 2 diabetes mellitus. However, the molecular mechanisms linking these two defects remain unknown. Elevated levels of apolipoprotein CIII (apoCIII) are associated not only with insulin resistance but also with cardiovascular disorders and inflammation. We now demonstrate that local apoCIII production is connected to pancreatic islet insulin resistance and beta-cell failure. An increase in islet apoCIII causes promotion of a local inflammatory milieu, increased mitochondrial metabolism, deranged regulation of beta-cell cytoplasmic free Ca2+ concentration ([Ca2+](i)) and apoptosis. Decreasing apoCIII in vivo results in improved glucose tolerance, and pancreatic apoCIII knockout islets transplanted into diabetic mice, with high systemic levels of the apolipoprotein, demonstrate a normal [Ca2+](i) response pattern and no hallmarks of inflammation. Hence, under conditions of islet insulin resistance, locally produced apoCIII is an important diabetogenic factor involved in impairment of beta-cell function and may thus constitute a novel target for the treatment of type 2 diabetes mellitus.
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| 4. |
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| 5. |
- Hedlund, Erik, 1958-
(författare)
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Yrkesofficersutbildning, yrkeskunnande och legitimitet : En studie av yrkesofficersprogrammet i spänningsfältet mellan förändring och tradition
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The new Swedish Armed Forces will be radically different from the previous invasion-oriented defence and the Armed Forces will be a smaller and more flexible organization, better adapted to the international sphere. With the aim of meeting up with the demands of the transformed Armed Forces posture for professional competence, the Regular Officer Programme (YOP) was introduced in the autumn of 1999.This dissertation aims at attempting to illustrate, address the problems and investigate to what degree the basic officer training of the Regular Officer Programme (Swedish: YOP) and the professional competence of newlygraduated Second Lieutenants can be seen as being legitimate within the scope of professional practices of the Swedish Armed Forces, and how this legitimacy can be described and understood.The theoretical framework of the dissertation is comprised of a sociocultural perspective and institutional theory. The five central concepts of the dissertation are: professional practice, institutional rules, professional competence, learning and legitimacy. The empirical elements of the dissertation were collected during 2001 and 2002 and comprise data from six part-studies. The informants were officer cadets after their first year of the Basic Officer Training Programme (YOP) and officers up to the rank of general. The methods for collecting data have been in the form of a questionnaire study, focus group conversations at thirteen military units, three document studies and a study with questions via e-mail. The questionnaire study was processed by using the computer programme SAS. The focus group conversations, the document studies and the answers via e-mail to questions were analyzed and put into categories contents wise according to the sentence category principle in positive and negative statements, respectively, in relation to YOP and the professional competence of the newly-graduated Second Lieutenants. Results show that both YOP as well as the professional competence of the newly-graduated Second Lieutenants cannot be regarded as being fully legitimate among the informants or within the all the professional practices of the Armed Forces.
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| 6. |
- Johansson, Cecilia
(författare)
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Högstadieungdomar skriver historia på bloggen : undervisning, literacy och historiemedvetande i ett nytt medielandskap
- 2014
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this thesis is to study the literacy formed when a class blog is used as a tool for students studying history and explore how this particular literacy is used to generate historical knowledge. The study was conducted during the course of a project in which ninth-grade students contributed entries to a common blog in the form of a diary written by individuals who experienced the Second World War. Its three major objectives were to study the students' perception of the blog in relation to their gender and level of historical knowledge; how they and their teacher esta-blished and used the formed literacy; and how the students related to this in the production of historical knowledge.In analyzing the results, a concept of literacy was used based on seven writing practices all linked to the new medium and history education. The study was based on a questionnaire, interviews and various student texts. In order to perform a content analysis on the study results a theoretical framework for historical conscious-ness was included. The results show that in using the writing practices a literacy characterized by colla-borative authorship was formed. The study concludes that this affects both what and how the students learn. Together they show each other that history is comprised of many small stories, not necessarily strictly coherent with the general history as told by their textbooks. Examining the students’ blog entries made a new learning process visible that enabled the enhancement of their historical consciousness.
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| 7. |
- Norlén, Filip, et al.
(författare)
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Occupational exposure to inorganic particles during pregnancy and birth outcomes : A nationwide cohort study in Sweden
- 2019
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim of this study was to investigate if occupational exposure to inorganic particles or welding fumes during pregnancy is associated with negative birth outcomes. Design A prospective national cohort study. Setting All single births from 1994 to 2012 in Sweden. Information on birth weight, preterm birth, small for gestational age, smoking habits, nationality, age, occupation, absence from work and education was obtained from nationwide registers. Exposure to inorganic particles (mg/m 3) was assessed from a job exposure matrix. Participants This study included all single births by occupationally active mothers (995 843). Outcome measures Associations between occupational exposures and negative birth outcomes in the form of low birth weight, preterm birth and small for gestational age. Results Mothers who had high exposure to inorganic particles and had less than 50 days (median) of absence from work during pregnancy showed an increased risk of preterm birth (OR 1.18; 95% CI 1.07 to 1.30), low birth weight (OR 1.32; 95% CI 1.18 to 1.48) as well as small for gestational age (OR 1.20; 95% CI 1.04 to 1.39). The increased risks were driven by exposure to iron particles. No increased risks were found in association with exposure to stone and concrete particles. High exposure to welding fumes was associated with an increased risk of low birth weight (OR 1.22; 95% CI 1.02 to 1.45) and preterm birth (OR 1.24; 95% CI 1.07 to 1.42). Conclusions The results indicate that pregnant women should not be exposed to high levels of iron particles or welding fumes.
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| 8. |
- Norlén, Filip, et al.
(författare)
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Occupational exposure to organic particles and combustion products during pregnancy and birth outcome in a nationwide cohort study in Sweden
- 2019
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Ingår i: Occupational and environmental medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 76:8, s. 537-544
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study if children of women exposed to organic particles and combustion products at work during pregnancy, have an increased risk of low birth weight, preterm birth or small for gestational age. Methods: A nationwide cohort of all occupationally active mothers and their children from single births during 1994 to the end of 2012 (1 182 138 observations) was formed. Information on birth outcome was obtained from the medical birth register. Information on absence from work, education, occupation, age, nationality and smoking habits was obtained from national registers. A job exposure matrix (FINJEM) was used to assess the exposure. Results: Pregnant women with low absence from work and high (>50th percentile) exposure to organic particles had an increased risk of giving birth to children with low birth weight (OR=1.19; 95% CI: 1.07 to 1.32), small for gestational age (OR=1.22; 95% CI: 1.07 to 1.38) or preterm birth (OR=1.17; 95% CI: 1.08 to 1.27). Subgroup analyses showed an increased risk of small for gestational age in association with exposure to oil mist. Exposure to oil mist and cooking fumes was associated with low birth weight. Paper and other organic dust was associated with preterm birth. Exposure to combustion products showed an increased risk of small for gestational age (OR=1.40; 95% CI: 1.15 to 1.71). Conclusions: The results indicate that occupational exposure to organic particles or combustion products during pregnancy is associated with restriction of fetal growth and preterm birth. More studies are needed to confirm a casual association.
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| 9. |
- Oström, Maria, et al.
(författare)
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Retinoic acid promotes the generation of pancreatic endocrine progenitor cells and their further differentiation into beta-cells
- 2008
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:7, s. e2841-
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Tidskriftsartikel (refereegranskat)abstract
- The identification of secreted factors that can selectively stimulate the generation of insulin producing beta-cells from stem and/or progenitor cells represent a significant step in the development of stem cell-based beta-cell replacement therapy. By elucidating the molecular mechanisms that regulate the generation of beta-cells during normal pancreatic development such putative factors may be identified. In the mouse, beta-cells increase markedly in numbers from embryonic day (e) 14.5 and onwards, but the extra-cellular signal(s) that promotes the selective generation of beta-cells at these stages remains to be identified. Here we show that the retinoic acid (RA) synthesizing enzyme Raldh1 is expressed in developing mouse and human pancreas at stages when beta-cells are generated. We also provide evidence that RA induces the generation of Ngn3(+) endocrine progenitor cells and stimulates their further differentiation into beta-cells by activating a program of cell differentiation that recapitulates the normal temporal program of beta-cell differentiation.
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| 10. |
- Pathipati, Stalin R., et al.
(författare)
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Diastereoselective Synthesis of Cyclopenta[c]furans by a Catalytic Multicomponent Reaction
- 2016
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 55:39, s. 11863-11866
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Tidskriftsartikel (refereegranskat)abstract
- A diastereoselective three-component reaction between alkynyl enones, aldehydes and secondary amines is reported. With the aid of a benign indium catalyst, a range of highly substituted cyclopenta[c]furan derivatives can be obtained in a single-step procedure. The formation of the stereodefined heterocyclic motifs takes place via in situ generation of enamines followed by two sequential cyclization steps.
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