| 1. |
- Dahlqvist, Per, et al.
(författare)
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Effects of postischemic environment on transcription factor and serotonin receptor expression after permanent focal cortical ischemia in rats
- 2003
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Ingår i: Neuroscience. - 1873-7544 .- 0306-4522. ; 119:3, s. 643-652
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Tidskriftsartikel (refereegranskat)abstract
- Housing rats in an enriched environment improves functional outcome after ischemic stroke, this may reflect neuronal plasticity in brain regions outside the lesion. Which components of the enriched environment that are of greatest importance for recovery after brain ischemia is uncertain. We have previously found that enriched environment and social interaction alone both improve functional recovery after focal cerebral ischemia, compared with isolated housing with voluntary wheel-running. In this study, the aim was to separate components of the enriched environment and investigate the effects on some potential mediators of improved functional recovery; such as the inducible transcription factors nerve growth factor-induced gene A (NGFI-A) and NGFI-B, and the glucocorticoid and serotonin systems. After permanent middle cerebral artery occlusion, rats were divided into four groups: individually housed with no equipment (deprived group), individually housed with free access to a running wheel (running group), housed together in a large cage with no equipment (social group) or in a large cage furnished with exchangeable bars, chains and other objects (enriched group). mRNA expression of inducible transcription factors, serotonin and glucocorticoid receptors was determined with in situ hybridisation 1 month after cerebral ischemia. Rats housed in enriched or social environments showed significantly higher mRNA expression of NGFI-A and NGFI-B in cortical regions outside the lesion and in the CA1 (cornu ammonis region of the hippocampus), compared with isolated rats with or without a running wheel. NGFI-A and NGFI-B mRNA expression in cortex and in CA1 was significantly correlated to functional outcome. 5-Hydroxytryptamine receptor 1A (5-HT1A) mRNA expression and binding, as well as 5-HT2A receptor mRNA expression were decreased in the hippocampus (CA4 region) of the running wheel rats. Mineralocorticoid receptor gene expression was increased in the dentate gyrus amongst wheel-running rats. No group differences were found in plasma corticosterone levels or mRNA levels of glucocorticoid receptor, corticotropin-releasing hormone, 5-HT2C or c-fos. In conclusion, we have found that social interaction is a major component of the enriched environment regarding the effects on NGFI-A and NGFI-B expression. These transcription factors may be important mediators of improved functional recovery after brain infarctions, induced by environmental enrichment. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.
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| 2. |
- Engstrand, Per O., 1955-, et al.
(författare)
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Mekmassainitiativet för energieffektivitet, e2mp-i
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Projektet har drivits som ett program för finansiering av forskning som ska utveckla ochdemonstrera tekniker som reducerar elenergiförbrukningen med 50% vid tillverkning avTMP och CTMP med bibehållna slutproduktegenskaper hos tryckpapper och kartong.Programmet är en del av skogsindustrins initiativ att under en tioårsperiod tillsammansmed svenska och norska finansiärer investera minst 200 Mkr för att nå detta radikalaeffektiviseringsmål. Ett uttalat mål för industriinitiativet är också att befästaforskningsnoderna vid FSCN i Sundsvall och PFI i Trondheim.Parallellt med Energimyndighetens finansiering, 30 Mkr, har Norges Forskningsråd satsat25 MNOK (2010‐14) i industriinitiativet, KK‐stiftelsen 36 MSEK (2011‐17) ochMittuniversitetet har finansierat12 MSEK. Industrins totala satsning kommer att överstiga100 MSEK redan vid utgången av 2017.Resultat från benchmarkingstudien BAT2012 av industrins modernaste TMP‐ och CTMPlinjersamt från demonstrationsskaleprojekt visas i rapporten. Projekten baseras delvis pågrundläggande forskningsprojekt genomförda inom FSCN´s KK‐stiftelse‐finansieradeforskningsprofil och projektet ”Filling the Gap” 31676‐, ISSN 1650‐5387 2014:57. Resultaten visar följande reduktionsnivåer; 28% TMP för news (Braviken), 14% TMP för SC(Kvarnsveden) och 21% CTMP för kartong (Skoghall).Utöver demoprojekten finns ytterligare tydliga potentialer beskrivna i övriga delprojekt:Processintensifiering och processmodifiering > 15%Processtabilitet via avancerad processanalys och reglering > 15%Kombinera effektivaste processavsnitt från benchmarking ca 25%Detta gör det troligt att det kommer att gå att i fullskaliga demonstrationsförsök validera50% elenergireduktion inom de tre produktområdena, förutsatt att fortsattforskningsfinansiering finns tillgänglig. Tre av de idéer till avknoppningsprojekt somframkommit under projektets gång har redan erhållit beslut om finansiering frånEnergimyndigheten 2015. Ytterligare projektförslag baserade på den här redovisadeforskningen kommer att ingå i ansökningar under 2016. Utöver energireduktion i själva TMP‐ och CTMP‐processerna har forskare vid FSCN lagt forskningsgrunden för hur manska kunna tillverka mycket starka förpackningsmaterial från dessa massatyper på ettenergieffektivt sätt. Även inom detta område kommer en ansökning omuppskalningsprojekt att skickas in.
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| 3. |
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| 4. |
- Rasmussen, Eva Rye, et al.
(författare)
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Genome-wide association study of angioedema induced by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker treatment.
- 2020
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Ingår i: The Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 20:6, s. 770-783
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Tidskriftsartikel (refereegranskat)abstract
- Angioedema in the mouth or upper airways is a feared adverse reaction to angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, which is used for hypertension, heart failure and diabetes complications. This candidate gene and genome-wide association study aimed to identify genetic variants predisposing to angioedema induced by these drugs. The discovery cohort consisted of 173 cases and 4890 controls recruited in Sweden. In the candidate gene analysis, ETV6, BDKRB2, MME, and PRKCQ were nominally associated with angioedema (p < 0.05), but did not pass Bonferroni correction for multiple testing (p < 2.89 × 10-5). In the genome-wide analysis, intronic variants in the calcium-activated potassium channel subunit alpha-1 (KCNMA1) gene on chromosome 10 were significantly associated with angioedema (p < 5 × 10-8). Whilst the top KCNMA1 hit was not significant in the replication cohort (413 cases and 599 ACEi-exposed controls from the US and Northern Europe), a meta-analysis of the replication and discovery cohorts (in total 586 cases and 1944 ACEi-exposed controls) revealed that each variant allele increased the odds of experiencing angioedema 1.62 times (95% confidence interval 1.05-2.50, p = 0.030). Associated KCNMA1 variants are not known to be functional, but are in linkage disequilibrium with variants in transcription factor binding sites active in relevant tissues. In summary, our data suggest that common variation in KCNMA1 is associated with risk of angioedema induced by ACEi or ARB treatment. Future whole exome or genome sequencing studies will show whether rare variants in KCNMA1 or other genes contribute to the risk of ACEi- and ARB-induced angioedema.
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| 5. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 7. |
- Andersson, Mattias, 1985, et al.
(författare)
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Dielectric strength of γ-radiation cross-linked, high vinyl-content polyethylene
- 2015
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Ingår i: European Polymer Journal. - : Elsevier BV. - 0014-3057. ; 64, s. 101-107
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Tidskriftsartikel (refereegranskat)abstract
- We explore γ-radiation cross-linking of high vinyl-content low-density polyethylene (LDPE) and its potential use as a high-voltage insulation material. Of the three investigated resins containing 1, 0.5 and 0.17 vinyl groups per 1000 carbons, respectively, only the highest vinyl-content material featured a sufficiently high gel content of more than 70% and hot-set elongation below 175%, when cross-linked with a γ-radiation dose of at least 68 kGy. Differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS) reveal that neither the crystallinity nor the lamellar thickness of the highest vinyl-content LDPE are negatively affected by γ-radiation cross-linking. As a result, we find that the dielectric strength, as characterized by electrical tree initiation experiments, can be maintained upon γ-radiation cross-linking.
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| 10. |
- Aranda-Guillén, Maribel, et al.
(författare)
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A polygenic risk score to help discriminate primary adrenal insufficiency of different etiologies.
- 2023
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Ingår i: Journal of internal medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 294:1, s. 96-109
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune Addison's disease (AAD) is the most common cause of primary adrenal insufficiency (PAI). Despite its exceptionally high heritability, tools to estimate disease susceptibility in individual patients are lacking. We hypothesized that polygenic risk score (PRS) for AAD could help investigate PAI pathogenesis in pediatric patients.We here constructed and evaluated a PRS for AAD in 1223 seropositive cases and 4097 controls. To test its clinical utility, we reevaluated 18 pediatric patients, whose whole genome we also sequenced. We next explored the individual PRS in more than 120 seronegative patients with idiopathic PAI.The genetic susceptibility to AAD-quantified using PRS-was on average 1.5 standard deviations (SD) higher in patients compared with healthy controls (p<2e-16), and 1.2 SD higher in the young patients compared with the old (p=3e-4). Using the novel PRS, we searched for pediatric patients with strikingly low AAD susceptibility and identified cases of monogenic PAI, previously misdiagnosed as AAD. By stratifying seronegative adult patients by autoimmune comorbidities and disease duration we could delineate subgroups of PRS suggesting various disease etiologies.The PRS performed well for case-control differentiation and susceptibility estimation in individual patients. Remarkably, a PRS for AAD holds promise as a means to detect disease etiologies other than autoimmunity.
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