| 1. |
- Carlsson, Lena M S, 1957, et al.
(författare)
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Long-term incidence of serious fall-related injuries after bariatric surgery in Swedish obese subjects.
- 2019
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Ingår i: International journal of obesity (2005). - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 43:4, s. 933-937
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Tidskriftsartikel (refereegranskat)abstract
- Obesity increases risk of falling, but the effect of bariatric surgery on fall-related injuries is unknown. The aim of this study was therefore to study the association between bariatric surgery and long-term incidence of fall-related injuries in the prospective, controlled Swedish Obese Subjects study. At inclusion, body mass index was≥34kg/m2 in men and ≥38kg/m2 in women. The surgery per-protocol group (n=2007) underwent gastric bypass (n=266), banding (n=376), or vertical banded gastroplasty (n=1365), and controls (n=2040) received usual care. At the time of analysis (31 December 2013), median follow-up was 19 years (maximal 26 years). Fall-related injuries requiring hospital treatment were captured using data from the Swedish National Patient Register. During follow-up, there were 617 first-time fall-related injuries in the surgery group and 513 in the control group (adjusted hazard ratio 1.21, 95% CI, 1.07-1.36; P=0.002). The incidence differed between treatment groups (P<0.001, log-rank test) and was higher after gastric bypass than after usual care, banding and vertical banded gastroplasty (adjusted hazard ratio 0.50-0.52, P<0.001 for all three comparisons). In conclusion, gastric bypass surgery was associated with increased risk of serious fall-related injury requiring hospital treatment.
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| 2. |
- Ekstrand, Eva-Maria, 1985-, et al.
(författare)
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Identifying targets for increased biogasproduction through chemical and organicmatter characterization of digestate from full‑scale biogas plants : what remains and why?
- 2022
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Ingår i: Biotechnology for Biofuels and Bioproducts. - London, United Kingdom : BioMed Central. - 2731-3654. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study examines the destiny of macromolecules in different full-scale biogas processes. From previousstudies it is clear that the residual organic matter in outgoing digestates can have significant biogas potential,but the factors dictating the size and composition of this residual fraction and how they correlate with the residualmethane potential (RMP) are not fully understood. The aim of this study was to generate additional knowledge of thecomposition of residual digestate fractions and to understand how they correlate with various operational and chemicalparameters. The organic composition of both the substrates and digestates from nine biogas plants operating onfood waste, sewage sludge, or agricultural waste was characterized and the residual organic fractions were linked tosubstrate type, trace metal content, ammonia concentration, operational parameters, RMP, and enzyme activity.Results: Carbohydrates represented the largest fraction of the total VS (32–68%) in most substrates. However, inthe digestates protein was instead the most abundant residual macromolecule in almost all plants (3–21 g/kg). Thedegradation efficiency of proteins generally lower (28–79%) compared to carbohydrates (67–94%) and fats (86–91%).High residual protein content was coupled to recalcitrant protein fractions and microbial biomass, either from thesubstrate or formed in the degradation process. Co-digesting sewage sludge with fat increased the protein degradationefficiency with 18%, possibly through a priming mechanism where addition of easily degradable substrates alsotriggers the degradation of more complex fractions. In this study, high residual methane production (> 140 L CH4/kgVS) was firstly coupled to operation at unstable process conditions caused mainly by ammonia inhibition (0.74 mgNH3-N/kg) and/or trace element deficiency and, secondly, to short hydraulic retention time (HRT) (55 days) relative tothe slow digestion of agricultural waste and manure.Conclusions: Operation at unstable conditions was one reason for the high residual macromolecule content andhigh RMP. The outgoing protein content was relatively high in all digesters and improving the degradation of proteinsrepresents one important way to increase the VS reduction and methane production in biogas plants. Post-treatment
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| 3. |
- Almstedt, Åsa, 1977-, et al.
(författare)
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Beyond Post-productivism : From Rural Policy Discource to Rural Diversity
- 2014
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Ingår i: European Countryside. - Berlin : Walter de Gruyter GmbH. - 1803-8417. ; 6:4, s. 297-306
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Tidskriftsartikel (refereegranskat)abstract
- There has been a strong discourse in public policy aimed at transforming rural places from venues of primary production into truly diverse socioeconomic landscapes. Yet conceptualisations of the rural as envisioned in the policy and politics of the ‘new economy’ often prove to be elusive on the ground. However, post-productive activity in rural areas has become a major focus for rural studies scholars. This paper investigates the ideas of post-productivism in the existing literature, and argues for a holistic understanding of post-productivism as an idea and political ambition rather than an imperative and irreversible change of rural economic activity. The purpose of the study is to make clear the division between post-productivism and the related concepts of post-production and post-productive activities in order to better understand processes of rural change in relation to different geographical contexts. It is argued that post-productivism as a concept stands apart from de facto post-production and alternative concepts such as multifunctionality and should be regarded as part of broader regional development discourses. The paper outlines several important fields in which post-productivism is a necessary component for rural transformation and development. While it is not always easily captured in indicators or empirical studies in rural locations, post- productivism exists at the level of discourse and planning and thus has real effects on the ground. The paper concludes by offering suggestions on how to apply the concepts of post-productivism, post-production and multifunctionality in future studies.
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| 4. |
- Benrick, Anna, 1979, et al.
(författare)
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Interleukin-6 gene knockout influences energy balance regulating peptides in the hypothalamic paraventricular and supraoptic nuclei.
- 2009
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Ingår i: Journal of neuroendocrinology. - : Wiley. - 1365-2826 .- 0953-8194. ; 21:7, s. 620-8
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin (IL)-6 is a pro-inflammatory cytokine that also affects metabolic function because IL-6 depleted (IL-6(-/-)) mice develop late-onset obesity. IL-6 appears to act in the central nervous system, presumably in the hypothalamus, to increase energy expenditure that appears to involve stimulation of the sympathetic nervous system. In the present study, we explored possible central mechanisms for the effects exerted by IL-6 on body fat. Therefore, we measured the effects of IL-6 depletion in IL-6(-/-) mice on expression of key hypothalamic peptide genes involved in energy balance by the real time polymerase chain reaction. Additionally, co-localisation between such peptides and IL-6 receptor alpha was investigated by immunohistochemistry. IL-6 deficiency decreased the expression of several peptides found in the paraventricular nucleus (PVN), which is a nucleus that has been attributed an adipostatic function. For example, corticotrophin-releasing hormone (CRH), which is reported to stimulate the sympathetic nervous system, was decreased by 40% in older IL-6(-/-) mice. Oxytocin, which is reported to prevent obesity, was also decreased in older IL-6(-/-) animals, as was arginine vasopressin (AVP). The IL-6 receptor alpha was abundantly expressed in the PVN, but also in the supraoptic nucleus, and was shown to be co-expressed to a high extent with CRH, AVP, oxytocin and thyrotrophin-releasing hormone. These data indicate that depletion of endogenous IL-6, a body fat suppressing cytokine, is associated with the decreased expression of CRH and oxytocin (i.e. energy balance regulating peptides) as well as AVP in the PVN. Because IL-6 receptor alpha is co-expressed with CRH, oxytocin and AVP, IL-6 could stimulate the expression of these peptides directly.
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| 5. |
- Bergengren, Lovisa, 1972-, et al.
(författare)
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Effectiveness and costs of an implemented primary HPV cervical screening programme in Sweden : A population based cohort study
- 2022
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Ingår i: Preventive Medicine Reports. - : Elsevier. - 2211-3355. ; 25
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Tidskriftsartikel (refereegranskat)abstract
- Swedish guidelines recommend cervical screening with primary HPV for women ≥ 30 years of age. The aim of this study was to compare an implemented HPV cervical screening programme in the Region of Örebro County from September 1, 2016, with the former cytology-based screening programme.The clinical effectiveness by means of number of high-grade squamous intraepithelial lesions (HSILs) and cervical cancer cases detected in histology within 12 months after the screening test, together with cost implications were the main outcomes. Data were retrieved from the Swedish National Cervical Screening Registry between the years 2014-2015 (cytology based screening) and 2017-2018(HPV based screening), including screening information such as invitations and cytology and histology diagnoses.The detection rate of HSIL + among women ≥ 30 years of age was 1.2 times higher with HPV screening, but data revealed an increase in direct colposcopy referral rate by 54% and a higher percentage of irrelevant findings (≤LSIL). Screening based on HPV for women ≥ 30 has increased yearly cost from 1 to 1.3 million EUR, while increasing the number of HSIL + identified. Two thirds of the total costs are from visits for screening samples in the programme.HPV screening detected more cases of HSIL + compared to cytology screening among women ≥ 30 although high colposcopy rate, high rate of clinical irrelevant findings and higher costs were shown in the HPV-based screening programme, which implies that alterations in the screening programme in the future are important to consider.
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| 6. |
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| 7. |
- Brouder, Patrick, et al.
(författare)
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Hyper-production : a new metric of multifinctionality
- 2015
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Ingår i: European Countryside. - : Walter de Gruyter. - 1803-8417. ; 7:3, s. 134-143
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Tidskriftsartikel (refereegranskat)abstract
- Multifunctionality has emerged as the dominant framework for understanding rural socioeconomic landscapes. The central claim of multifunctionality – that rural regions need to be understood as being made up of more than just traditional uses – has led to the incorporation of new rural activities into regional development plans, e.g., tourism. In some places, such post-productive activity is perceived to be slowly replacing productive uses of the land, e.g., agriculture/forestry. However, there is limited empirical evidence to support such claims. Drawing on previous research and data from the Swedish countryside this paper shows that, even as the number of persons employed within traditional activities decreases, the economic output per areal unit and per labour hour is increasing over time and traditional uses still occupy the majority of rural space. Hyper-production is introduced as a new metric for understanding multifunctional regions going forward. The complementary union of economic mainstays, such as agriculture, and newer activities with more quality-of-life benefits, such as tourism, is highlighted in terms of economic diversification, job creation and local social capital development, while the conflict-prone intersection of these two modes is also acknowledged. Understanding hyper-production as a key metric of multifunctionality is thus argued as integral to planning and developing resilient rural regions now and for the future.
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| 8. |
- Cornelissen, Johannes H C, et al.
(författare)
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Global negative vegetation feedback to climate warming responses of leaf litter decomposition rates in cold biomes
- 2007
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 10:7, s. 619-627
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Tidskriftsartikel (refereegranskat)abstract
- Whether climate change will turn cold biomes from large long-term carbon sinks into sources is hotly debated because of the great potential for ecosystem-mediated feedbacks to global climate. Critical are the direction, magnitude and generality of climate responses of plant litter decomposition. Here, we present the first quantitative analysis of the major climate-change-related drivers of litter decomposition rates in cold northern biomes worldwide.Leaf litters collected from the predominant species in 33 global change manipulation experiments in circum-arctic-alpine ecosystems were incubated simultaneously in two contrasting arctic life zones. We demonstrate that longer-term, large-scale changes to leaf litter decomposition will be driven primarily by both direct warming effects and concomitant shifts in plant growth form composition, with a much smaller role for changes in litter quality within species. Specifically, the ongoing warming-induced expansion of shrubs with recalcitrant leaf litter across cold biomes would constitute a negative feedback to global warming. Depending on the strength of other (previously reported) positive feedbacks of shrub expansion on soil carbon turnover, this may partly counteract direct warming enhancement of litter decomposition.
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| 9. |
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| 10. |
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| 11. |
- Hansson, Caroline, 1981, et al.
(författare)
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Influence of ghrelin on the central serotonergic signaling system in mice
- 2014
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Ingår i: Neuropharmacology. - : Elsevier BV. - 0028-3908. ; 79, s. 498-505
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Tidskriftsartikel (refereegranskat)abstract
- The central ghrelin signaling system engages key pathways of importance for feeding control, recently shown to include those engaged in anxiety-like behavior in rodents. Here we sought to determine whether ghrelin impacts on the central serotonin system, which has an important role in anxiety. We focused on two brain areas, the amygdala (of importance for the mediation of fear and anxiety) and the dorsal raphe (i.e. the site of origin of major afferent serotonin pathways, including those that project to the amygdala). In these brain areas, we measured serotonergic turnover (using HPLC) and the mRNA expression of a number of serotonin-related genes (using real-time PCR). We found that acute central administration of ghrelin to mice increased the serotonergic turnover in the amygdala. It also increased the mRNA expression of a number of serotonin receptors, both in the amygdala and in the dorsal raphe. Studies in ghrelin receptor (GHS-R1A) knock-out mice showed a decreased mRNA expression of serotonergic receptors in both the amygdala and the dorsal raphe, relative to their wild-type littermates. We conclude that the central serotonin system is a target for ghrelin, providing a candidate neurochemical substrate of importance for ghrelin's effects on mood. © 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
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| 12. |
- Hellström, Mats, et al.
(författare)
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Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis.
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 445:7129, s. 776-80
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Tidskriftsartikel (refereegranskat)abstract
- In sprouting angiogenesis, specialized endothelial tip cells lead the outgrowth of blood-vessel sprouts towards gradients of vascular endothelial growth factor (VEGF)-A. VEGF-A is also essential for the induction of endothelial tip cells, but it is not known how single tip cells are selected to lead each vessel sprout, and how tip-cell numbers are determined. Here we present evidence that delta-like 4 (Dll4)-Notch1 signalling regulates the formation of appropriate numbers of tip cells to control vessel sprouting and branching in the mouse retina. We show that inhibition of Notch signalling using gamma-secretase inhibitors, genetic inactivation of one allele of the endothelial Notch ligand Dll4, or endothelial-specific genetic deletion of Notch1, all promote increased numbers of tip cells. Conversely, activation of Notch by a soluble jagged1 peptide leads to fewer tip cells and vessel branches. Dll4 and reporters of Notch signalling are distributed in a mosaic pattern among endothelial cells of actively sprouting retinal vessels. At this location, Notch1-deleted endothelial cells preferentially assume tip-cell characteristics. Together, our results suggest that Dll4-Notch1 signalling between the endothelial cells within the angiogenic sprout serves to restrict tip-cell formation in response to VEGF, thereby establishing the adequate ratio between tip and stalk cells required for correct sprouting and branching patterns. This model offers an explanation for the dose-dependency and haploinsufficiency of the Dll4 gene, and indicates that modulators of Dll4 or Notch signalling, such as gamma-secretase inhibitors developed for Alzheimer's disease, might find usage as pharmacological regulators of angiogenesis.
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| 13. |
- Kalén, Mattias, et al.
(författare)
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Combination of reverse and chemical genetic screens reveals angiogenesis inhibitors and targets.
- 2009
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Ingår i: Chemistry & biology. - : Elsevier BV. - 1879-1301 .- 1074-5521. ; 16:4, s. 432-41
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Tidskriftsartikel (refereegranskat)abstract
- We combined reverse and chemical genetics to identify targets and compounds modulating blood vessel development. Through transcript profiling in mice, we identified 150 potentially druggable microvessel-enriched gene products. Orthologs of 50 of these were knocked down in a reverse genetic screen in zebrafish, demonstrating that 16 were necessary for developmental angiogenesis. In parallel, 1280 pharmacologically active compounds were screened in a human cell-based assay, identifying 28 compounds selectively inhibiting endothelial sprouting. Several links were revealed between the results of the reverse and chemical genetic screens, including the serine/threonine (S/T) phosphatases ppp1ca, ppp1cc, and ppp4c and an inhibitor of this gene family; Endothall. Our results suggest that the combination of reverse and chemical genetic screens, in vertebrates, is an efficient strategy for the identification of drug targets and compounds that modulate complex biological systems, such as angiogenesis.
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| 14. |
- Karlsson, Linda, 1972
(författare)
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Functions of platelet-derived growth factor-A during organogenesis
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The formation of organs during embryonic development is calledorganogenesis. This process is regulated by the genes residing in the genome.Thousands of genes are likely to be involved, but there are increasing evidence thatmost organs develop through similar processes performed by conserved networks ofgene products from the same multi-gene families.Platelet-derived growth factor-A (PDGF-A) is a classical growth factor thatexerts its function via a receptor tyrosine kinase, PDGF receptor-á (PDGFR-á). Micedeficient for PDGF-A and PDGFR-á have been analysed in order to elucidate thefunction of PDGF-A in vivo. Deletion of either gene leads to perturbed developmentof several organ systems.In the central nervous system, PDGF-A is critical for the proliferation andspreading of oligodendrocyte progenitors. Loss of PDGF-A leads to defectiveoligodendrogenesis and hypomyelination.In the lung, PDGF-A is critical for multiplication and spreading ofmesenchymal alveolar smooth muscle cell progenitors along the branching bronchialtree. Loss of PDGF-A leads to loss of alveolar smooth muscle cells resulting in a lungdefect reminiscent of lung emphysema.In the skin, PDGF-A is proposed to promote proliferation of a subset ofPDGFR-á positive mesenchymal cells. These cells are subsequently recruited tobecome dermal fibroblasts and the mesenchymal components of the hair follicle: thedermal papilla and the dermal sheath. Lack of PDGF-A leads to fewer cells at theselocations, causing malformed hair follicles, thinner hair and failure to enter the secondhair cycle.A similar role is suggested for PDGF-A in the intestine. PDGF-A promotesproliferation of a subset of PDGFR-á positive mesenchymal progenitor cells that areinvolved in villus formation. At the onset of villus formation, these cells form clusters(called villus clusters) that remain localised at the tip of the growing villus. Our dataimplicate that the villus cluster is instrumental in villus morphogenesis. In the absenceof either PDGF-A or PDGFR-á , fewer villi are formed and those generated areabnormal in size and shape.In summary, we suggest that PDGF-A is a component in one of the conservedgene product networks, where the general principle for PDGF-A is to promoteproliferation (and possibly spreading at some locations) of progenitor cells thatsubsequently differentiate into cell types with important functions in organogenesis.In the lung, skin and hair follicles, and the gastrointestinal villus, the PDGF-A dependent cells are important in epithelial folding.
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| 15. |
- Karlsson-Lindahl, Linda, 1972, et al.
(författare)
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Heparanase affects food intake and regulates energy balance in mice.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Mutation of the melanocortin-receptor 4 (MC4R) is the most frequent cause of severe obesity in humans. Binding of agouti-related peptide (AgRP) to MC4R involves the co-receptor syndecan-3, a heparan sulfate proteoglycan. The proteoglycan can be structurally modified by the enzyme heparanase. Here we tested the hypothesis that heparanase plays a role in food intake behaviour and energy balance regulation by analysing body weight, body composition and food intake in genetically modified mice that either lack or overexpress heparanase. We also assessed food intake and body weight following acute central intracerebroventricular administration of heparanase; such treatment reduced food intake in wildtype mice, an effect that was abolished in mice lacking MC4R. By contrast, heparanase knockout mice on a high-fat diet showed increased food intake and maturity-onset obesity, with up to a 40% increase in body fat. Mice overexpressing heparanase displayed essentially the opposite phenotypes, with a reduced fat mass. These results implicate heparanase in energy balance control via the central melanocortin system. Our data indicate that heparanase acts as a negative modulator of AgRP signaling at MC4R, through cleavage of heparan sulfate chains presumably linked to syndecan-3.
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| 16. |
- Karlsson, Michael, 1970-, et al.
(författare)
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OMNIBUS NEWS: Engagement or bussed?
- 2015
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Konferensbidrag (refereegranskat)abstract
- During the summer of 2013 the municipal public bus system, Karlstadbuss, installed television sets (BUSS-TV) on all city buses. These TV sets are airing user-generated content, and traffic information, weather forecasts as well as news from the hybrid commercial/public service broadcaster TV4. This paper addresses the phenomenon from the theoretical intersection of communication geography and journalism studies. This means understanding the city-buses, at once mobile and semi-public spaces, as decorated with a new “communicative texture” that is renegotiating the time-space nexus traditionally tied to news consumption. Furthermore, it potentially implies that a basic news diet become more or less dispersed amongst commuters across the city, and across previous class-demarcations that would engender divergent news diets. This constitutes a potential challenge to the notion of the fragmented news audience and related worries over the increased number of “news avoiders”. From previous research we know that news consumption, even accidental, is linked with political and civic engagement. In an era where media consumption is increasingly fragmented or even avoided, the buss-news reinstalls the almost inescapable news of the 1970’s albeit in a highly situated and limited context. Nevertheless, this new space of ‘news on the move’ is yet to be explored theoretically and empirically. Thus, we ask about the role of Karlstadbuss as a carrier of omnibus news in the media ecology. The paper uses data derived from representative surveys (Värmlands-SOM) conducted before (2010) and after (2014) the introduction of BUSS-TV to study the impact of travelling with the city-buses on political interest and civic engagement as well as general news interest and consumption.
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| 17. |
- Keskitalo, E. Carina H., 1974-, et al.
(författare)
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Rural-urban policies : changing conceptions of the human-environment relationship
- 2017
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Ingår i: Globalisation and change in forest ownership and forest use. - London : Palgrave Macmillan. - 9781137571151 - 9781137571168 ; , s. 183-224
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Bokkapitel (refereegranskat)abstract
- This chapter describes how understandings of the "rural" have progressed from a focus on either decline or amenity, whereby these more simplified understandings can be seen to have had an impact on rural policy development. The chapter argues that rural areas, including forests, need to be understood in relation to both production and integration with urban landscapes. It thus illustrates the role of both historical processes and policy in creating current understandings of the rural: drawing upon an example from the Swedish case, it amongst others shows that a redistributive tax system has played a larger and more crucial role than rural policy in retaining active rural areas in Sweden.
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| 18. |
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| 19. |
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| 20. |
- Lundmark, Linda, 1975-, et al.
(författare)
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International migration, self-employment and restructuring through tourism in sparsely populated areas
- 2014
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Ingår i: Scandinavian Journal of Hospitality and Tourism. - London : Taylor & Francis. - 1502-2250 .- 1502-2269. ; 14:4, s. 422-440
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Tidskriftsartikel (refereegranskat)abstract
- Previous research has shown that different forms of migration in general, and tourism-related international migration in particular, could act as potential drivers for various forms of rural transformations. This paper investigates self-employment in tourism among foreign-born people in rural Sweden. The questions addressed in this paper are: What is the magnitude of self-employment, and what types of business do in-migrants run, in rural areas? A discussion on the extent to which in-migrants to rural areas contribute to rural restructuring through self-employment in tourism follows. The results are analyzed by drawing on theories connected to restructuring and ideas of the “new economy”. The longitudinal, individual and geo-referenced database ASTRID with official Swedish register data is used to identify foreign-born people self-employed in tourism in Sweden. Self- employment is more common for in-migrants coming from culturally proximate Western countries, followed by Asia and the Middle East. The length of time in Sweden plays a significant role in the incidence of self-employment in tourism, with restaurants dominating as the type of establishment. It can be discussed how much restaurants help invigorate the economy of rural areas, and how much they contribute to rural change and transformation in qualitative terms.
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| 21. |
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| 22. |
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| 23. |
- Ryan Bengtsson, Linda, 1976-, et al.
(författare)
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Röster från den svenska musikbranschen : Utmaningar och lösningar under pandemin
- 2024
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Ingår i: Musik – musikproduktion – musikbransch. - Dalarna : Dalarna University. - 9789188679710 ; , s. 121-134
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Bokkapitel (refereegranskat)abstract
- Covid-19 och de restriktioner som följde i pandemins spår förändrade musikbranschens förutsättningar över en natt. Scener och klubbar tvingades stänga när det infördes förbud mot allmänna sammankomster och alla uppmanades att hålla avstånd. Festivaler, turnéer och konserter ställdes in. Men hur påverkades och förhöll sig den svenska musikbranschen till restriktionerna under pandemin? Detta kapitel ger en bild av tiden under pandemin utifrån små och medelstora svenska musikaktörer. Aktörer som står utanför de stora major-bolagen och som är aktiva utanför Sveriges storstadsregioner. Utgångspunkten är enstudie som initierades när Sverige införde begränsningar av allmännasammankomster 2020 och som pågick fram till sommaren 2022. Kapitlet redogör för musikaktörers reaktioner, ageranden och de olika faser branschens aktörer genomgick under denna märkliga tid – från desperation till innovativt samarbete.
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| 24. |
- Salomé, Nicolas, et al.
(författare)
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On the central mechanism underlying ghrelin's chronic pro-obesity effects in rats: new insights from studies exploiting a potent ghrelin receptor antagonist.
- 2009
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Ingår i: Journal of neuroendocrinology. - : Wiley. - 1365-2826 .- 0953-8194. ; 21:9, s. 777-85
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, we explore the central nervous system mechanism underlying the chronic central effects of ghrelin with respect to increasing body weight and body fat. Specifically, using a recently developed ghrelin receptor antagonist, GHS-R1A (JMV2959), we investigate the role of GHS-R1A in mediating the effects of ghrelin on energy balance and on hypothalamic gene expression. As expected, in adult male rats, chronic central treatment with ghrelin for 14 days, when compared to vehicle-treated control rats, resulted in an increased body weight, lean mass and fat mass (assessed by dual X-ray absorptiometry), dissected white fat pad weight, cumulative food intake, food efficiency, respiratory exchange ratio and a decrease of energy expenditure. Co-administration of the ghrelin receptor antagonist JMV2959 suppressed/blocked the majority of these effects, with the notable exception of ghrelin-induced food intake and food efficiency. The hypothesis emerging from these data, namely that GHS-R1A mediates the chronic effects of ghrelin on fat accumulation, at least partly independent of food intake, is discussed in light of the accompanying data regarding the hypothalamic genes coding for peptides and receptors involved in energy balance regulation, which were found to have altered expression in these studies.
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| 25. |
- Sandström, Linda, 1973-, et al.
(författare)
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Speech intelligibility in Parkinson's disease patients with zona incerta deep brain stimulation
- 2015
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Ingår i: Brain and Behavior. - : John Wiley & Sons. - 2162-3279 .- 2162-3279. ; 5:10
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo investigate the effects of l-dopa (Levodopa) and cZi-DBS (deep brain stimulation in caudal zona incerta) on spontaneous speech intelligibility in patients with PD (Parkinson's disease).Materials and MethodsSpontaneous utterances were extracted from anechoic recordings from 11 patients with PD preoperatively (off and on l-dopa medication) and 6 and 12 months post bilateral cZi-DBS operation (off and on stimulation, with simultaneous l-dopa medication). Background noise with an amplitude corresponding to a clinical setting was added to the recordings. Intelligibility was assessed through a transcription task performed by 41 listeners in a randomized and blinded procedure.ResultsA group-level worsening in spontaneous speech intelligibility was observed on cZi stimulation compared to off 6 months postoperatively (8 adverse, 1 positive, 2 no change). Twelve months postoperatively, adverse effects of cZi-DBS were not frequently observed (2 positive, 3 adverse, 6 no change). l-dopa administered preoperatively as part of the evaluation for DBS operation provided the overall best treatment outcome (1 adverse, 4 positive, 6 no change).ConclusionscZi-DBS was shown to have smaller negative effects when evaluated from spontaneous speech compared to speech effects reported previously. The previously reported reduction in word-level intelligibility 12 months postoperatively was not transferred to spontaneous speech for most patients. Reduced intelligibility due to cZi stimulation was much more prominent 6 months postoperatively than at 12 months.
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| 26. |
- Schéle, Erik, 1980, et al.
(författare)
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Interleukin-6 Receptor alpha is Co-localised with Melanin-Concentrating Hormone in Human and Mouse Hypothalamus
- 2012
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Ingår i: Journal of Neuroendocrinology. - : Wiley. - 0953-8194. ; 24:6, s. 930-943
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin (IL)-6 deficient mice develop mature-onset obesity. Furthermore, i.c.v. administration of IL-6 increases energy expenditure, suggesting that IL-6 centrally regulates energy homeostasis. To investigate whether it would be possible for IL-6 to directly influence the energy homeostasis via hypothalamic regulation in humans and rodents, we mapped the distribution of the ligand binding IL-6 receptor a (IL-6Ra) in this brain region. In the human hypothalamus, IL-6Ra-immunoreactivity was detected in perikarya and first-order dendrites of neurones. The IL-6Ra-immunoreactive (-IR) neurones were observed posterior to the level of the interventricular foramen. There, IL-6Ra-IR neurones were located in the lateral hypothalamic, perifornical, dorsal and posterior hypothalamic areas, the hypothalamic dorsomedial nucleus and in the zona incerta. In the caudal part of the hypothalamus, the density of the IL-6Ra-IR neurones gradually increased. Double-labelling immunofluorescent studies demonstrated that IL-6Ra immunoreactivity was localised in the same neurones as the orexigenic neuropeptide, melanin-concentrating hormone (MCH). By contrast, IL-6Ra-immunoreactivity was not observed in the orexin B-IR neurones. To determine whether the observed expression of IL-6Ra is evolutionary conserved, we studied the co-localisation of IL-6Ra with MCH and orexin in the mouse hypothalamus, where IL-6Ra-immunoreactivity was present in numerous MCH-IR and orexin-IR neurones. Our data demonstrate that the MCH neurones of the human hypothalamus, as well as the MCH and orexin neurones of the mouse hypothalamus, contain IL-6Ra. This opens up the possibility that IL-6 influences the energy balance through the MCH neurones in humans, and both MCH and orexin neurones in mice.
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| 27. |
- Shao, Linus Ruijin, 1964, et al.
(författare)
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Clomiphene citrate causes aberrant tubal apoptosis and estrogen receptor activation in rat fallopian tube: implications for tubal ectopic pregnancy.
- 2009
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Ingår i: Biology of reproduction. - : Oxford University Press (OUP). - 0006-3363 .- 1529-7268. ; 80:6, s. 1262-71
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Tidskriftsartikel (refereegranskat)abstract
- Clomiphene citrate (CC) therapy for disorders of anovulatory infertility has been linked to an increased frequency of tubal ectopic pregnancy. Although CC enhances apoptotic processes in the ovaries, villi, and decidual tissues, its effect on apoptosis in the fallopian tube is unknown. Here, we show that chronic treatment with CC induces tubal apoptosis, but not necrosis, through an intrinsic mitochondria-dependent signaling pathway in vivo. The apoptosis was specific to epithelial cells in the isthmus, and the damage was reversed with 17beta-estradiol (E2); however, pretreatment or concomitant treatment with E2 did not protect against tubal apoptosis induced by chronic treatment with CC. Chronic treatment activated estrogen receptors (ESRs), particularly cilia-localized ESR2A (formerly ERbeta2). In contrast to E2, acute treatment of superovulating rats with a high dose of CC or the ESR2-selective agonist 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN) significantly delayed the transport of oocyte-cumulus complexes through the fallopian tube. Our findings suggest that in response to chronic CC therapy, isthmus-specific apoptosis of epithelial cells and activation of cilia-ESR2A act in parallel to block gamete and embryo passage through the fallopian tube, eventually resulting in tubal ectopic pregnancy.
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| 28. |
- Shao, Linus Ruijin, 1964, et al.
(författare)
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Down-Regulation of Cilia-Localized IL-6R{alpha} by 17{beta}-Estradiol in Mouse and Human Fallopian Tubes.
- 2009
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Ingår i: American journal of physiology. Cell physiology. - : American Physiological Society. - 0363-6143 .- 1522-1563. ; 297:1
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Tidskriftsartikel (refereegranskat)abstract
- The action of Interleukin-6 (IL-6) impacts female reproduction. Although IL-6 was recently shown to inhibit cilia activity in human fallopian tubes in vitro, the molecular mechanisms underlying IL-6 signaling to tubal function remain elusive. Here, we investigate the cellular localization, regulation, and possible function of two IL-6 receptors (IL-6Ralpha and gp130) in mouse and human fallopian tubes in vivo. We show that IL-6Ralpha is restricted to the cilia of epithelial cells in both mouse and human fallopian tubes. Exogenous 17beta-estradiol (E2), but not progesterone (P4), causes a time-dependent decrease in IL-6Ralpha expression which is blocked by the estrogen receptor (ER) antagonist ICI 182,780. Exposure of different ER-selective agonists, PTT or DPN, demonstrated an ER subtype-specific regulation of IL-6Ralphaalpha in mouse fallopian tubes. In contrast to IL-6Ralpha, gp130 was detected in tubal epithelial cells in mice but not in humans. In humans, gp130 was found in the muscle cells and was decreased in the periovulatory and luteal phases during the reproductive cycles, indicating a species-specific expression and regulation of gp130 in the fallopian tube. Expression of tubal IL-6Ralpha and gp130 in IL-6 knockout mice was found to be normal; however, E2 treatment increased IL-6Ralpha, but not gp130, in IL-6 knockout mice compared to wild-type mice. Furthermore, expression levels of IL-6Ralpha, but not gp130, decreased in parallel with estrogenic accelerated oocyte-cumulus complex (OCC) transport in mouse fallopian tubes. Our findings unveil a potential role for cilia-specific IL-6Ralpha in the regulation of OCC transport and suggest an estrogen-regulatory pathway of IL-6Ralpha in the fallopian tube. Key words: estrogen, IL-6R, cilia, fallopian tube.
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| 29. |
- Skålén, Per, 1972-, et al.
(författare)
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Public Service Innovation : A Public Service dominant logic view
- 2016
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Ingår i: WHAT'S AHEAD IN SERVICE RESEARCH?. - Neapel, Italien : UNIV NAPLES FEDERICO II, DEPT ECON MGMT & INST. - 9791220013840 ; , s. 756-770
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Konferensbidrag (refereegranskat)abstract
- The paper departs from research on Public Service Dominant Logic (PSDL) to advance a framework of service innovation for the public sector. It continues the incorporation of Service-Dominant Logic (SDL) concepts that has been initiated by PSDL research to the public management domain, in particular the notions of resource integration and value propositions is incorporated to PSDL, and builds a conceptual framework of Public Service Innovation (PSI). This framework consist of three resource integration processes, users value creation in use, users and personnel's' value cocreation in direct interaction and internal value facilitation, and suggest that these three processes contribute to service innovation by integrating resources into value propositions. Through an empirical study of primary care the paper finds that the framework describes how PSI is conducted in practice in the public management domain. The paper contributes to articulate a PSDL-based service innovation framework. It also contributes by grounding this framework in an empirical study. In addition, it contributes by elaborating PSDL in such a way that may be drawn on to study public service innovation.
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| 30. |
- Thysell, Elin, et al.
(författare)
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Clinical and biological relevance of the transcriptomic-based prostate cancer metastasis subtypes MetA-C
- 2022
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 16:4, s. 846-859
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Tidskriftsartikel (refereegranskat)abstract
- To improve treatment of metastatic prostate cancer, the biology of metastases needs to be understood. We recently described three subtypes of prostate cancer bone metastases (MetA-C), based on differential gene expression. The aim of this study was to verify the clinical relevance of these subtypes and to explore their biology and relations to genetic drivers. Freshly-frozen metastasis samples were obtained as hormone-naive (n = 17), short-term castrated (n = 21), or castration-resistant (n = 65) from a total of 67 patients. Previously published sequencing data from 573 metastasis samples were also analyzed. Through transcriptome profiling and sample classification based on a set of predefined MetA-C-differentiating genes, we found that most metastases were heterogeneous for the MetA-C subtypes. Overall, MetA was the most common subtype, while MetB was significantly enriched in castration-resistant samples and in liver metastases, and consistently associated with poor prognosis. By gene set enrichment analysis, the phenotype of MetA was described by high androgen response, protein secretion and adipogenesis, MetB by high cell cycle activity and DNA repair, and MetC by epithelial-to-mesenchymal transition and inflammation. The MetB subtype demonstrated single nucleotide variants of RB transcriptional corepressor 1 (RB1) and loss of 21 genes at chromosome 13, including RB1, but provided independent prognostic value to those genetic aberrations. In conclusion, a distinct set of gene transcripts can be used to classify prostate cancer metastases into the subtypes MetA-C. The MetA-C subtypes show diverse biology, organ tropism, and prognosis. The MetA-C classification may be used independently, or in combination with genetic markers, primarily to identify MetB patients in need of complementary therapy to conventional androgen receptor-targeting treatments.
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| 31. |
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| 32. |
- Wänström, Johan, 1970-, et al.
(författare)
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Riskfyllda beslut? : Skolnedläggelsers avtryck i kommunala valresultat
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I diskussioner med kommunföreträdare framkommer ofta berättelser och farhågor kopplade till kommunala skolnedläggelser. Det finns en allmän uppfattning om att skolnedläggelser ofta utvecklas till besvärliga situationer som inte sällan påverkar det styrande partiets resultat negativt i det efterkommande valet till kommunfullmäktige.Vi har därför studerat valresultaten från valen till kommunfullmäktige 2006 och 2010 i 46 av det Nationella kommunforskningsprogrammets 47 medlemskommuner (Stockholm är inte med i materialet). Vi har jämfört valresultaten för det styrande partiet (det parti som innehar kommunstyrelseordförandeposten) samt det största oppositionspartiet i de kommuner som lagt ner åtminstone en grundskola under de aktuella mandatperioderna med valresultaten i de kommuner som inte har lagt ner några grundskolor.De genomsnittliga förändringarna i valresultaten i de kommuner som lagt ner skolor skiljer sig inte från de kommuner som inte lagt ner någon skola. Det finns heller inga statistiska belägg i studien för att det spelar någon roll om beslut om skolnedläggelser fattas tidigt eller sent under en mandatperiod; om skolan ligger i tätort eller på landsbygden; om kommunen är stor eller liten samt om det är en eller flera skolor som läggs ner.Trots att det är betydligt vanligare att socialdemokratiska styren tar beslut om skolnedläggelser än borgerliga styren finns det heller inget som tyder på att partifärgen spelar någon roll för relation mellan beslut om nedläggelse och valresultat. De här slutsatserna avspeglas även i att andelen maktskiften t. o. m. är lägre i kommuner som lagt ner skolor än i de som inte lagt ner några skolor.Istället stödjer studien tidigare forskning som pekar på att förändringar i nationella väljaropinioner, såsom uttryckt i resultaten i riksdagsvalet, har stor påverkan på valen till kommunfullmäktigen samt att enskilda sakfrågor från den gångna mandatperioden sällan gör några stora avtryck i de efterkommande valresultaten.
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