| 1. |
- Frazier-Wood, Alexis C., et al.
(författare)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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| 2. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
- 2011
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:8, s. 753-60
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.
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| 3. |
- Abbott, Benjamin W., et al.
(författare)
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Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire : an expert assessment
- 2016
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- As the permafrost region warms, its large organic carbon pool will be increasingly vulnerable to decomposition, combustion, and hydrologic export. Models predict that some portion of this release will be offset by increased production of Arctic and boreal biomass; however, the lack of robust estimates of net carbon balance increases the risk of further overshooting international emissions targets. Precise empirical or model-based assessments of the critical factors driving carbon balance are unlikely in the near future, so to address this gap, we present estimates from 98 permafrost-region experts of the response of biomass, wildfire, and hydrologic carbon flux to climate change. Results suggest that contrary to model projections, total permafrost-region biomass could decrease due to water stress and disturbance, factors that are not adequately incorporated in current models. Assessments indicate that end-of-the-century organic carbon release from Arctic rivers and collapsing coastlines could increase by 75% while carbon loss via burning could increase four-fold. Experts identified water balance, shifts in vegetation community, and permafrost degradation as the key sources of uncertainty in predicting future system response. In combination with previous findings, results suggest the permafrost region will become a carbon source to the atmosphere by 2100 regardless of warming scenario but that 65%-85% of permafrost carbon release can still be avoided if human emissions are actively reduced.
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| 4. |
- Alfredsson, Magnus, et al.
(författare)
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Funktionskriterier för vägkonstruktioner : Förstudie
- 2010
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Det projekt som här rapporteras har som syfte att identifiera och beskriva de svårigheter och möjligheter som totalentreprenader medför, respektive erbjuder, för alla parter. Målet är att utveckla totalentreprenader på ett sådant sätt att branschens effektivitet ökas. Denna rapport är en förstudie där det studerats vilka krav som byggherren ska ställa på utföraren av en vägkonstruktion i en totalentreprenad med funktionsansvar och hur utföraren ska verifiera kraven. Arbetet har genomförts med medlemmar från olika aktörer i branschen och omfattat främst litteraturstudier och intervjuer. Kunskaper och erfarenheter har sammanställts och analyserats för att slutligen kondenseras ned till ett antal förslag till fortsatt arbete.Förstudien har pekat ut ett antal områden som viktiga för att påskynda framtida utveckling av totalentreprenader:Terminologi – idag råder viss begreppsförvirringAnalys av funktionella krav i tidigare projektTrafikantkravMiljökravUtveckling av funktionella krav i samverkanVäghållarekonomiRegelbetingade begränsningar av funktionella kravUppföljning och underlättande av erfarenhetsackumuleringImplementering av nya mått och mätmetoder
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| 5. |
- Ekblad, Jonas, et al.
(författare)
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Impact on rutting from introduction of increased axle loads in Finland
- 2020
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Ingår i: The international journal of pavement engineering. - : Taylor and Francis Ltd.. - 1029-8436 .- 1477-268X.
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Tidskriftsartikel (refereegranskat)abstract
- In 2013, Finland introduced legislation increasing gross vehicle weights (GVW) on a number of trucks. Since the actual impact on road damage is nearly impossible to quantify in advance, the present analysis of road surface measurements is intended to provide knowledge regarding the impact on road damage. Rutting is influenced by many conflated phenomena. To indicate and capture the effect on road damage due to the new maximum GVW for certain truck- and trailer combinations, the analysis follows two different but mutually supporting lines of reasoning, empirical and theoretical, respectively. Analysis of measured rut depth is supported by theoretical calculations. Theoretical findings clearly indicate that the relative increase in road damage induced by higher GVW is larger than the increase in relative payload capacity. There was a rapid fleet shift towards heavier trucks after 2013, and statistical (empirical) analysis of road surface measurements shows an increase in rutting after this introduction.
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| 6. |
- Ferguson, Michael A, et al.
(författare)
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Increased platelet mitochondrial respiration after cardiac arrest and resuscitation as a potential peripheral biosignature of cerebral bioenergetic dysfunction
- 2016
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Ingår i: Journal of Bioenergetics and Biomembranes. - : Springer Science and Business Media LLC. - 1573-6881 .- 0145-479X. ; 48:3, s. 269-279
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Tidskriftsartikel (refereegranskat)abstract
- Cardiac arrest (CA) results in a sepsis-like syndrome with activation of the innate immune system and increased mitochondrial bioenergetics.OBJECTIVE: To determine if platelet mitochondrial respiration increases following CA in a porcine pediatric model of asphyxia-associated ventricular fibrillation (VF) CA, and if this readily obtained biomarker is associated with decreased brain mitochondrial respiration. CA protocol: 7 min of asphyxia, followed by VF, protocolized titration of compression depth to systolic blood pressure of 90 mmHg and vasopressor administration to a coronary perfusion pressure greater than 20 mmHg.PRIMARY OUTCOME: platelet integrated mitochondrial electron transport system (ETS) function evaluated pre- and post-CA/ROSC four hours after return of spontaneous circulation (ROSC). Secondary outcome: correlation of platelet mitochondrial bioenergetics to cerebral bioenergetic function. Platelet maximal oxidative phosphorylation (OXPHOSCI+CII), P < 0.02, and maximal respiratory capacity (ETSCI+CII), P < 0.04, were both significantly increased compared to pre-arrest values. This was primarily due to a significant increase in succinate-supported respiration through Complex II (OXPHOSCII, P < 0.02 and ETSCII, P < 0.03). Higher respiration was not due to uncoupling, as the LEAKCI + CII respiration (mitochondrial respiration independent of ATP-production) was unchanged after CA/ROSC. Larger increases in platelet mitochondrial respiratory control ratio (RCR) compared to pre-CA RCR were significantly correlated with lower RCRs in the cortex (P < 0.03) and hippocampus (P < 0.04) compared to sham respiration. Platelet mitochondrial respiration is significantly increased four hours after ROSC. Future studies will identify mechanistic relationships between this serum biomarker and altered cerebral bioenergetics function following cardiac arrest.
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| 7. |
- Hörbeck, Elin, 1984, et al.
(författare)
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Dissecting the impact of complement component 4A in bipolar disorder.
- 2023
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Ingår i: Brain, behavior, and immunity. - 1090-2139. ; 116, s. 150-159
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Tidskriftsartikel (refereegranskat)abstract
- The genetic overlap between schizophrenia (SZ) and bipolar disorder (BD) is substantial. Polygenic risk scores have been shown to dissect different symptom dimensions within and across these two disorders. Here, we focused on the most strongly associated SZ risk locus located in the extended MHC region, which is largely explained by copy numbers of the gene coding for complement component 4A (C4A). First, we utilized existing brain tissue collections (N = 1,202 samples) and observed no altered C4A expression in BD samples. The generated C4A seeded co-expression networks displayed no genetic enrichment for BD. To study if genetically predicted C4A expression discriminates between subphenotypes of BD, we applied C4A expression scores to symptom dimensions in a total of 4,739 BD cases with deep phenotypic data. We identified a significant association between C4A expression and psychotic mood episodes in BD type 1 (BDI). No significant association was observed between C4A expression and the occurrence of non-affective psychotic episodes in BDI, the psychosis dimensions in the total BD sample, or any other subphenotype of BD. Overall, these results points to a distinct role of C4A in BD that is restricted to vulnerability for developing psychotic symptoms during mood episodes in BDI.
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| 8. |
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| 9. |
- Kilbaugh, Todd J, et al.
(författare)
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Persistently Altered Brain Mitochondrial Bioenergetics After Apparently Successful Resuscitation From Cardiac Arrest.
- 2015
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 4, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Although advances in cardiopulmonary resuscitation have improved survival from cardiac arrest (CA), neurologic injury persists and impaired mitochondrial bioenergetics may be critical for targeted neuroresuscitation. The authors sought to determine if excellent cardiopulmonary resuscitation and postresuscitation care and good traditional survival rates result in persistently disordered cerebral mitochondrial bioenergetics in a porcine pediatric model of asphyxia-associated ventricular fibrillation CA.
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| 10. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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