| 1. |
- Barg, Sebastian, 1969-, et al.
(författare)
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Granule docking and cargo release in pancreatic β-cells
- 2008
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Ingår i: Biochemical Society Transactions. - 0300-5127 .- 1470-8752. ; 36:Pt 3, s. 294-299
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Tidskriftsartikel (refereegranskat)abstract
- Biphasic insulin secretion is required for proper insulin action and is observed not only in vivo, but also in isolated pancreatic islets and even single beta-cells. Late events in the granule life cycle are thought to underlie this temporal pattern. In the last few years, we have therefore combined live cell imaging and electrophysiology to study insulin secretion at the level of individual granules, as they approach the plasma membrane, undergo exocytosis and finally release their insulin cargo. In the present paper, we review evidence for two emerging concepts that affect insulin secretion at the level of individual granules: (i) the existence of specialized sites where granules dock in preparation for exocytosis; and (ii) post-exocytotic regulation of cargo release by the fusion pore.
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| 2. |
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| 3. |
- Levin, Max, 1969, et al.
(författare)
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ATP depletion and cell death in the neonatal lamb ductus arteriosus
- 2005
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Ingår i: Pediatr Res. - 0031-3998. ; 57:6, s. 801-805
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Tidskriftsartikel (refereegranskat)abstract
- Postnatal constriction of the full-term ductus arteriosus produces cell death and remodeling of the ductus wall. Using a bioluminescence imaging technique, we found that after birth, the lamb ductus develops ATP, glucose, and glycogen depletion in addition to hypoxia. In vitro studies showed that cell death correlates best with ATP depletion and is most marked when both glucose and oxygen are severely depleted; in addition, the degree of ATP depletion found in vivo is sufficient to account for the extensive degree of cell death that occurs after birth. Under hypoxic conditions, the immature ductus is more capable of preserving its ATP supply than the mature ductus as a result of increased glucose availability, glycogen stores, and glucose utilization. However, the immature ductus is just as susceptible as the mature ductus to ATP depletion when glucose supplies are restricted. The extensive degree of cell death that occurs in the newborn ductus after birth is associated primarily with ATP depletion. The increased glycolytic capacity of the immature ductus may enable it to tolerate episodes of hypoxia and nutrient shortage, making it more resistant to developing postnatal cell death and permanent closure.
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| 4. |
- Lindblad, Sverker, 1946, et al.
(författare)
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In education we trust: on handling the COVID-19 Pandemic in the Swedish welfare state
- 2021
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Ingår i: Zeitschrift für Erziehungswissenschaft. - : Springer Science and Business Media LLC. - 1434-663X .- 1862-5215. ; 24:2, s. 503-519
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Tidskriftsartikel (refereegranskat)abstract
- Keeping schools open was an active strategy in Sweden to meet the threats of the COVID-19 pandemic. In this article we analyze how a collection of welfare state agents with different tasks, resources and interests in interaction formed an assemblage in their responses to the pandemic and how education thereby became part of a strategy to keep the society going. The inquiries concern what this tells us about education as framed and constrained as a part of society. Our observations are based on statements presented by the government and public agencies, mass media and websites. We identified an assemblage of interwoven agents such as institutions, laws, regulations and recommendations, pandemic manuals, statistics and media. All these were brought together by actions and ideas to handle a pandemic when there were no preventive vaccines. The overarching principle was to educate the population to competent actions in dealing with the pandemic. To keep schools open was part of that principle combined with caretaking ambitions. This assemblage looked like a centralistic machine but it was not; risks were pushed back to local authorities and schools. In conclusion, we note that education is vital in the overarching strategy to deal with the pandemic in Sweden in terms of trust in people and governmentality.
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| 5. |
- Lindblad, Sverker, 1946, et al.
(författare)
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School lockdown? Comparative analyses of responses to the COVID-19 pandemic in European countries
- 2021
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Ingår i: European Educational Research Journal. - : SAGE Publications. - 1474-9041. ; 20:5, s. 564-583
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this article is to analyse how education and schooling took part in handling the early phase of the COVID-19 pandemic in eight European countries (Denmark, Finland, Germany, Greece, Italy, Norway, Poland and Sweden). The focus is on primary education and on decisions to close schools, or not. Our research was informed by assemblage theory in order to analyse how different components interacted in developing societal responses to mitigate the pandemic. The research was designed as a comparative case study of practical reasoning in diverse contexts. Data sources were the mass media and statements from governments and authorities. Our analyses showed that decisions to close schools, or not, were based on two alternative discourses on schooling. Closing primary schools was a preventive measure underlined by discourses of schools as places for infection. Keeping primary schools open was underlined by a discourse in which schools were conceived of as a place for social supportive measures and caring. Furthermore, the closing alternative was often combined with attempts to replace school practices by distance learning or computerized instruction. Legal constitutions and lawmaking were of significant importance in selecting discourses and the relative impact of different components, mostly political or medical, in responding to the pandemic.
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| 6. |
- Lindqvist, Anders, et al.
(författare)
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Effects of oxygen tension on energetics of cultured vascular smooth muscle.
- 2002
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Ingår i: American Journal of Physiology: Heart and Circulatory Physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 283:1, s. 110-117
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Tidskriftsartikel (refereegranskat)abstract
- Chronic hypoxia is a clinically important condition known to cause vascular abnormalities. To investigate the cellular mechanisms involved, we kept rings of a rat tail artery for 4 days in hypoxic culture (HC) or normoxic culture (NC) (PO(2) = 14 vs. 110 mmHg) and then measured contractility, oxygen consumption (JO(2)), and lactate production (J(lac)) in oxygenated medium. Compared with fresh rings, basal ATP turnover (J(ATP)) was decreased in HC, but not in NC, with a shift from oxidative toward glycolytic metabolism. JO(2) during mitochondrial uncoupling was reduced by HC but not by NC. Glycogen stores were increased 40-fold by HC and fourfold by NC. Maximum tension in response to norepinephrine and the JO(2) versus tension relationship (JO(2) vs. high K(+) elicited force) were unaffected by either HC or NC. Force transients in response to caffeine were increased in HC, whereas intracellular Ca(2+) wave activity during adrenergic stimulation was decreased. Protein synthesis rate was reduced by HC. The results show that long-term hypoxia depresses basal energy turnover, impairs mitochondrial capacity, and alters Ca(2+) homeostasis, but does not affect contractile energetics. These alterations may form a basis for vascular damage by chronic hypoxia.
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| 7. |
- Lindqvist, Anders, et al.
(författare)
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Inhibition of calcium entry preserves contractility of arterial smooth muscle in culture
- 1997
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Ingår i: Journal of Vascular Research. - 1423-0135. ; 34:2, s. 103-108
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Tidskriftsartikel (refereegranskat)abstract
- The addition of the growth stimulator fetal calf serum (FCS, 10%) to rings of rat tail artery causes an increase in [Ca2+]i, accompanied by contraction. This response was inhibited by the calcium entry blocker verapamil (1 microM). To investigate the effect of Ca2+ entry blockade on growth and contractility, rings of rat tail artery were cultured for 4 days in medium with or without FCS and then mounted for tension registration and stimulated with noradrenaline (NA) or high-K+ solution. In cultured rings growth was quantitated by [3H]-thymidine incorporation and increase in protein contents. FCS in the medium stimulated DNA synthesis by about 2-fold and increased protein contents by about 70%. The growth-stimulated cultured rings developed less force than freshly prepared rings (2.2 +/- 0.3 vs. 8.3 +/- 1.0 mN/mm). The addition of 1 microM verapamil to the medium during culture increased maximal NA-evoked force to 5.0 +/- 0.4 mN/mm but had no effect on the increases in DNA synthesis and protein contents. Force developed by growth-arrested rings, cultured in the absence of FCS, was not different from that of freshly prepared rings (7.2 +/- 0.6 mM/mm). Verapamil did not affect maximal force in these rings. Similar responses were seen when contraction was elicited by high-K+ solution. We conclude that verapamil, present during culture, preserves contractility of arterial smooth muscle, and that this effect is not parallel to inhibition of growth.
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| 8. |
- Lindqvist, Anders, et al.
(författare)
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Long-term effects of Ca(2+) on structure and contractility of vascular smooth muscle
- 1999
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Ingår i: American Journal of Physiology: Cell Physiology. - 1522-1563. ; 277:1, s. 64-73
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Tidskriftsartikel (refereegranskat)abstract
- Culture of dispersed smooth muscle cells is known to cause rapid modulation from the contractile to the synthetic cellular phenotype. However, organ culture of smooth muscle tissue, with maintained extracellular matrix and cell-cell contacts, may facilitate maintenance of the contractile phenotype. To test the influence of culture conditions, structural, functional, and biochemical properties of rat tail arterial rings were investigated after culture. Rings were cultured for 4 days in the absence and presence of 10% FCS and then mounted for physiological experiments. Intracellular Ca(2+) concentration ([Ca(2+)](i)) after stimulation with norepinephrine was similar in rings cultured with and without FCS, whereas force development after FCS was decreased by >50%. The difference persisted after permeabilization with beta-escin. These effects were associated with the presence of vasoconstrictors in FCS and were dissociated from its growth-stimulatory action. FCS treatment increased lactate production but did not affect ATP, ADP, or AMP contents. The contents of actin and myosin were decreased by culture but similar for all culture conditions. There was no effect of FCS on calponin contents or myosin SM1/SM2 isoform composition, nor was there any appearance of nonmuscle myosin. FCS-stimulated rings showed evidence of cell degeneration not found after culture without FCS or with FCS + verapamil (1 microM) to lower [Ca(2+)](i). The decreased force-generating ability after culture with FCS is thus associated with increased [Ca(2+)](i) during culture and not primarily caused by growth-associated modulation of cells from the contractile to the synthetic phenotype.
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| 9. |
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| 10. |
- Lindqvist, Anders
(författare)
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Phenotypic modulation of vascular smooth muscle in organ culture
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Contraction of blood vessels for the regulation of blood flow and pressure is dependent on vascular smooth muscle cells (VSMC) located in the medial layer of the vascular wall. Adult, differentiated VSMC have a well developed contractile system and a low rate of proliferation. Under the influence of hormones, growth factors, inflammatory mediators and tissue factors, cells may modulate to a ”synthetic” phenotype, characterized by diminished contractility, a high rate of proliferation, and a tendency to migrate out of the organized tissue. Such cells are believed to form the ”neointima”, a thickening of the innermost layer of the wall characteristic of responses to endothelial injury, and important for the development of atherosclerotic lesions and of restenosis following vascular surgery. To study conditions of importance for maintaining the vessel wall in its contractile state, it is desirable to develop methods to keep blood vessels in organ culture, whereby tissue factors are preserved and experimental conditions can be well controlled. The aim of this thesis work was to study contractile and metabolic properties as well as biochemical composition and receptor expression in an arterial preparation (rat tail artery) kept in organ culture. After 4 days of culture arterial rings the morphology of the tissue was well preserved, but signs of phenotypic modulation were observed, particularly in the areas adjacent to the cut ends of the rings, where PDGF receptors appeared and the differentiation marker calponin was decreased. Culture with fetal calf serum (FCS) as growth promotor caused decreased contractility and ultrastructural signs of tissue damage. Detailed examination of this phenomenon disclosed that it is mainly caused by increased intracellular [Ca 2+ ]i , stimulated by vasoconstrictors present in FCS. Tight control of intracellular [Ca 2+ ]i is thus essential for tissue preservation. Cultured rings showed increased rate of lactate production but decreased O2 consumption, such that ATP production rate was the same as in fresh rings. Culture under hypoxia, however, caused reduced ATP production, suggesting decreased rate of energy consuming processes, such as protein turnover. Cultured rings maintained tension in hypoxic solution, in contrast to fresh rings. Reasons for this might be the increased reliance on glycolysis, and also an altered pattern of intracellular Ca 2+ waves, as revealed by laser scanning confocal microscopy. These results show that organ culture of vascular smooth muscle is useful for studying early events during phenotypic modulation in response to a variety of stimuli.
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