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- Saliba-Gustafsson, P., et al.
(författare)
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Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy
- 2019
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 660-675
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Tidskriftsartikel (refereegranskat)abstract
- Background Hyperlipidaemia is a major risk factor for cardiovascular disease, and atherosclerosis is the underlying cause of both myocardial infarction and stroke. We have previously shown that the Pro251 variant of perilipin-2 reduces plasma triglycerides and may therefore be beneficial to reduce atherosclerosis development. Objective We sought to delineate putative beneficial effects of the Pro251 variant of perlipin-2 on subclinical atherosclerosis and the mechanism by which it acts. Methods A pan-European cohort of high-risk individuals where carotid intima-media thickness has been assessed was adopted. Human primary monocyte-derived macrophages were prepared from whole blood from individuals recruited by perilipin-2 genotype or from buffy coats from the Karolinska University hospital blood central. Results The Pro251 variant of perilipin-2 is associated with decreased intima-media thickness at baseline and over 30 months of follow-up. Using human primary monocyte-derived macrophages from carriers of the beneficial Pro251 variant, we show that this variant increases autophagy activity, cholesterol efflux and a controlled inflammatory response. Through extensive mechanistic studies, we demonstrate that increase in autophagy activity is accompanied with an increase in liver-X-receptor (LXR) activity and that LXR and autophagy reciprocally activate each other in a feed-forward loop, regulated by CYP27A1 and 27OH-cholesterol. Conclusions For the first time, we show that perilipin-2 affects susceptibility to human atherosclerosis through activation of autophagy and stimulation of cholesterol efflux. We demonstrate that perilipin-2 modulates levels of the LXR ligand 27OH-cholesterol and initiates a feed-forward loop where LXR and autophagy reciprocally activate each other; the mechanism by which perilipin-2 exerts its beneficial effects on subclinical atherosclerosis.
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| 3. |
- Henry, C., et al.
(författare)
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Women’s entrepreneurship policy : A 13-nation cross-country comparison
- 2017
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Ingår i: Entrepreneurial ecosystems and growth of women's entrepreneurship. - : Edward Elgar Publishing. - 9781785364624 - 9781785364617 ; , s. 244-278
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Public policy is a key element within the entrepreneurial ecosystem in that policy has the potential to shape venture creation behavior and entrepreneurial outcomes. In response to studies documenting a gender gap in entrepreneurial activity, government attention to women’s entrepreneurship has increased in the past two decades. Nevertheless, there are few cross-cultural studies to inform policy development. This 13-nation study draws on gender and institutional theory to report on the status of female-focused SME/entrepreneurship policies and to ask: How - and to what extent - do women’s entrepreneurship policies differ among countries? A common methodological approach is used to identify gaps in the policy-practice nexus, highlighting countries where policy is weak but practice is strong and vice versa. Recommendations for future research are advanced.
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| 4. |
- Ahl, Amanda, et al.
(författare)
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Balancing formal and informal success factors perceived by supply chain stakeholders : A study of woody biomass energy systems in Japan
- 2018
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Ingår i: Journal of Cleaner Production. - : Elsevier. - 0959-6526 .- 1879-1786. ; 175, s. 50-59
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Tidskriftsartikel (refereegranskat)abstract
- Small-scale woody biomass energy systems have an inherent ability to aid in emissions reduction while stimulating local economies and, as collective energy systems, are strongly connected to supply chain design based on local conditions and stakeholder integration. Despite an abundance of forest area alongside the promotion of biomass in energy policies, however, woody biomass utilization still remains low in Japan. The woody biomass supply chain, considered as a socio-technical system, involves a complex, cross-sectoral stakeholder network in which inter-organizational dynamics necessitates well-organized management based on an understanding of formal factors such as technology, as well as informal factors such as social relations and culture. In this paper, success factor perceptions from across the woody biomass supply chain are investigated based on semi-structured interviews with four stakeholders in the Kyushu region of Japan. Identified success factors here are: 1) respect of values & traditions, 2) transportation infrastructure, 3) business model integration, 4) relationship & trust, 5) local vitalization and 6) biomass quality control. A convergence as well as divergence of perceptions are observed, involving both formal and informal dimensions. Aiming to balance perceptions and to enable long-term success of woody biomass in Japan, a series of policy implications are drawn, including cross-ministerial integration, knowledge building on wood logistics, forest certification, local coordinators, biomass quality control standards and a feed-in-tariff for heat. This paper suggests a new arena of policy-making based on the importance of considering both informal and formal dimensions in energy policy.
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| 7. |
- Ström, Jonathan, et al.
(författare)
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The association between gaba-modulators and clostridium difficile infection - A matched retrospective case-control study
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective Recently, metabolomics studies have suggested that the neurotransmitter ã-amino butyric acid (GABA) may modulate C. difficile infection (CDI) pathogenesis. In the present study, we investigated the association between GABA-modulating pharmaceuticals and CDI development. Methods In July-December 2013, we performed a matched, retrospective case-control study in Skåne county, Sweden, to assess the association between the use of GABA-modulators (defined as regular use of at least one of the following: zolpidem, zopiclone, benzodiazepines, gabapentin, pregabalin or baclofen) and CDI. Multivariate regression models, adjusted for known risk factors for CDI, were fitted to assess the associations and a propensity score-adjusted analysis was performed. Results The study included 292 cases and 292 matched controls. In a multivariate regression model only recent antibiotic use (clindamycin, cephalosporins and fluoroquinolones) and nursing home residency was significantly associated with CDI. The regular use of any GABA-modulator was not associated with CDI (OR = 1.07, 95%CI 0.69-1.66, p = 0.76). The association between regular use of the selective GABA-agonist zolpidem and CDI trended towards significance (OR = 2.31, 95%CI 0.91-5.86, p = 0.078). These associations remained when only cases treated with antibiotics were included. Corresponding findings for zolpidem was observed in a propensity-score adjusted analysis (OR = 2.52, 95% CI 0.91-6.97, p = 0.075). Severe initial CDI was significantly associated with CDI recurrence (OR = 3.77, 95% CU 1.20-11.86, p = 0.023). Conclusion This study did not identify a general association between GABA-modulators and CDI. A trend towards a significant association between zolpidem and CDI was observed, an association that should be re-assessed in a study appropriately powered for this particular hypothesis.
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