| 1. |
- Bandaru, Sashidar, et al.
(författare)
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Targeting filamin A reduces macrophage activity and atherosclerosis. : Filamin A in atherogenesis
- 2019
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Ingår i: Circulation. - 1524-4539. ; 140:1, s. 67-79
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Tidskriftsartikel (refereegranskat)abstract
- The actin-binding protein FLNA (filamin A) regulates signal transduction important for cell locomotion, but the role of macrophage-specific FLNA during atherogenesis has not been explored.We analyzed FLNA expression in human carotid atherosclerotic plaques by immunofluorescence. We also produced mice with Flna-deficient macrophages by breeding conditional Flna-knockout mice ( Flna o/fl) with mice expressing Cre from the macrophage-specific lysosome M promoter ( LC). Atherosclerosis in vivo was studied by transplanting bone marrow from male Flna o/fl/ LC mice to atherogenic low-density lipoprotein receptor-deficient ( Ldlr-/-) mice; and by infecting Flna o/fl and Flna o/fl/ LC mice with AdPCSK9 (adenoviral vector overexpressing proprotein convertase subtilisin/kexin type 9). Furthermore, C57BL/6 mice were infected with AdPCSK9 and then treated with the calpain inhibitor calpeptin to inhibit FLNA cleavage.We found that macrophage FLNA expression was higher in advanced than in intermediate human atherosclerotic plaques. Flna o/fl/ LC macrophages proliferated and migrated less than controls; expressed lower levels of phosphorylated AKT and ERK1/2; exhibited reduced foam cell formation and lipid uptake; and excreted more lipids. The deficiency of Flna in macrophages markedly reduced the size of aortic atherosclerotic plaques in both Ldlr-/-BMT: Flnao/fl/LC and AdPCSK9-infected Flna o/fl/ LC mice. Intima/media ratios and numbers of CD68-positive macrophages in atherosclerotic plaques were lower in Flna-deficient mice than in control mice. Moreover, we found that STAT3 interacts with a calpain-cleaved carboxyl-terminal fragment of FLNA. Inhibiting calpain-mediated FLNA cleavage with calpeptin in macrophages reduced nuclear levels of phosphorylated STAT3, interleukin 6 secretion, foam cell formation, and lipid uptake. Finally, calpeptin treatment reduced the size of atherosclerotic plaques in C57BL/6 mice infected with AdPCSK9.Genetic inactivation of Flna and chemical inhibition of calpain-dependent cleavage of FLNA impaired macrophage signaling and function, and reduced atherosclerosis in mice, suggesting that drugs targeting FLNA may be useful in the treatment of atherosclerosis.
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| 2. |
- Carli, V, et al.
(författare)
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A Naturalistic, European Multi-Center Clinical Study of Electrodermal Reactivity and Suicide Risk Among Patients With Depression
- 2022
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Ingår i: Frontiers in psychiatry. - : Frontiers Media SA. - 1664-0640. ; 12, s. 765128-
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Tidskriftsartikel (refereegranskat)abstract
- Background:Electrodermal hyporeactivity has been proposed as a marker of suicidal risk. The EUDOR-A study investigated the prevalence of electrodermal hyporeactivity among patients with depression and its association with attempted and completed suicide.Methods:Between August 2014 and March 2016, 1,573 in- and outpatients with a primary diagnosis of depression (active or remission phase) were recruited at 15 European psychiatric centers. Each patient was followed-up for 1 year. Electrodermal activity was assessed at baseline with the ElectroDermal Orienting Reactivity Test. Data on the sociodemographic characteristics, clinical diagnoses, and treatment of the subjects were also collected. The severity of the depressive symptoms was assessed through the Montgomery–Asberg Depression Rating Scale. Information regarding number, time, and method of suicide attempts was gathered at baseline and at the end of the 1-year follow-up. The same data were collected in case of completed suicide.Results:Hyporeactive patients were shown to be significantly more at risk of suicide attempt compared to reactive patients, both at baseline and follow-up. A sensitivity of 29.86% and a positive predictive value (PPV) of 46.77% were found for attempted suicide at baseline, while a sensitivity of 35.36% and a PPV of 8.92% were found for attempted suicide at follow-up. The sensitivity and PPV for completed suicide were 25.00 and 0.61%, respectively. However, when controlled for suicide attempt at baseline, the association between hyporeactivity and follow-up suicide attempt was no longer significant. The low number of completed suicides did not allow any analysis.
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| 3. |
- Ekstrand, Britten
(författare)
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Kursvärderingar som underlag för kvalitetsutveckling
- 2004
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Ingår i: Kursvärdering för studentinflytande och kvalitetsutveckling. - Stockholm : Högskoleverket. ; , s. 59-70
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- I detta bidrag tas utgångspunkt i hur framtagningen av några policydokument för kursvärderingsarbete kännetecknats av ett gränsöverskridande samarbete, samlade erfarenheter och aktiva studenter. En översyn av hur genomförandet lyckats och i vilken utsträckning kursvärderingar ligger till grund för kvalitetsutvecklingsarbetet har undersökts. Exemplet kommer från Högskolan Kristianstad.
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| 4. |
- Ekstrand, Joakim
(författare)
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Currency Markets - Equilibrium and Expectations
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The thesis consists of three essays on currency markets, equilibrium and expectations. The first essay examines currency markets in the setting of a temporary equilibrium model with two currencies and two central banks, where consumers have one-point expectations. Assuming that both central banks use floating exchange rate policies it is shown that if consumers have common expectations the current exchange rate will equal the expected future exchange rate. Under the assumptions made, there exist an equilibrium for the economy in the case where both central banks apply floating exchange rate policies as well as in the case where the banks co-operate and use fixed exchange rate policies. The possibilities for a single central bank to sustain a fixed exchange rate are discussed. Under some expectations, the economy may have more than one equilibrium exchange rate and these are related to different equilibrium allocations. In the second essay, a temporary equilibrium model with two currencies and where consumers have expectations on goods and currency prices with finite support is studied. Consequences for the individual consumer problem and equilibrium allocations are analyzed. State prices are defined for the case where asset markets are complete and these are used to derive conditions for consumers to meet increased risk with a variation in the portfolio of currencies, thus precluding precautionary saving. Equilibrium currency prices and adjustments in currency and good prices to a variation in the initial currency portfolio are examined. Perceived Pareto dominance is defined. It is argued that to get an allocation perceived to Pareto dominate the given equilibrium allocation consumers need more expensive portfolios. The third essay considers the determination of currency prices in an overlapping generations economy, with or without uncertainty. The economy with currencies is compared to an economy with money. For the case where there is no uncertainty and consumers have perfect foresight it is shown that currency prices may be chosen arbitrarily at one date but that the currency prices at other dates are then uniquely determined and constant over time. The analysis is extended to an economy with uncertainty where consumers are assumed to have rational expectations. It is shown that a given equilibrium allocation is consistent with constant as well as highly volatile currency prices. In general the currency prices and the exchange rate are only required to satisfy a martingale property. But if currency prices are assumed to depend only on a finite past history then they are forced to be constant over states and time. An equilibrium allocation may be realized also with incorrect expectations, about the currency prices, as long as expectations are consistent with the equilibrium portfolio values.
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| 5. |
- Ekstrand, Joakim, et al.
(författare)
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Differential inhibition of neurogenesis and angiogenesis by corticosterone in rats stimulated with electroconvulsive seizures
- 2008
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Ingår i: Progress in Neuro-Psychopharmacology and Biological Psychiatry. - : Elsevier BV. - 0278-5846. ; 32:6, s. 1466-1472
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Forskningsöversikt (refereegranskat)abstract
- Antidepressant drugs and electroconvulsive seizure (ECS)-treatment, an animal model of electroconvulsive therapy, induce neurogenesis in adult rats. Stress and high levels of corticosterone (CORT) on the contrary inhibit neurogenesis. Hippocampal neurogenesis has been described to occur in an angiogenic niche where proliferation of neural progenitors takes place in an environment with active vascular growth. Here we investigate the effect of ECS-treatment on the proliferation of endothelial cells and neuronal precursors in hippocampus of CORT-treated rats. Bromodeoxyuridine (BrdU) was used to identify dividing cells. The number of newborn neuronal precursors and endothelial cells was quantified in the subgranular zone (SGZ) and the molecular layer (ML) of the dentate gyrus. The increase in neuronal precursor proliferation in the SGZ following ECS-treatment was not inhibited by elevated levels of CORT despite CORT strongly inhibiting ECS-induced endothelial cell proliferation. Also in the ML CORT-treatment inhibited the ECS-induced angiogenic response. We conclude that despite common factors regulating neurogenesis and angiogenesis, ECS-induced proliferation of neuronal precursors can take place even if the angiogenic response is blunted. Whether inhibition of angiogenesis affects other steps in the chain of events leading to the formation of fully integrated granule neurons remains to be elucidated. (C) 2008 Elsevier Inc. All rights reserved.
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| 6. |
- Ekstrand, Joakim, et al.
(författare)
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Environmental enrichment, exercise and corticosterone affect endothelial cell proliferation in adult rat hippocampus and prefrontal cortex.
- 2008
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940. ; 442, s. 203-207
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Tidskriftsartikel (refereegranskat)abstract
- Stress and environmental enrichment have opposing effects on cerebral cellular plasticity. Stress-induced disturbances in neuronal and glial plasticity have been implicated in the pathophysiology of affective disorders. Patients with depression often show volume reductions in specific brain regions. The mechanisms behind these changes are not well understood, but animal studies have indicated that increased levels of glucocorticoids and stress have negative impact on the neuronal and glial cell populations. On the contrary, enriched environment and physical activity have positive effects. In this study we have examined the effect of corticosterone (CORT), environmental enrichment (EE) and running on angiogenesis in hippocampus and prefrontal cortex (PFC). We demonstrate a dramatic inhibition in endothelial cell proliferation in these brain regions in CORT-treated rats. Environmental enrichment had the opposite effect and stimulated endothelial cell proliferation both in the hippocampus and in the PFC. Running had a stimulatory effect in hippocampus, but not in the PFC. We suggest that the angiostatic effect of CORT demonstrated in this study might be paralleled in human subjects exposed to high levels of stress hormones for prolonged periods of time. Raised cortisol levels in depressed or old patients could, by reducing endothelial cell formation/turnover, lead to rarefaction and aging of the vascular bed, and as a result, neuronal function could be impaired. It is tempting to speculate that a physically and intellectually active life may protect against stress-induced vascular changes. Therapeutic agents also targeting the cerebral vasculature could consequently constitute a new tool in the combat of stress-related disorders.
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