Metalmusik - En studie om metalmusikens genrer och kultur samt dess plats i skolan

Det huvudsakliga syftet med denna studie är att undersöka metal som kultur och livsstil. Stu-dien ger även en inblick i hur vanligt det är att lyssna på och spela metalmusik bland gymnasieelever på det estetiska programmet med musikinriktning. Studien baseras på både kvalitativa och kvantitativa studier. Elever från två gymnasieskolor svarade på en enkätundersökning och två lärare intervjuades. Resultatet visar att det finns ett intresse av metalmusik bland eleverna som deltog i enkätundersökningen. Det visar även att det finns ett intresse av spela metal i skolan. En av informanterna tror även att det kan finnas ett behov av lärare med metalkompetens.Metal music - A study about the genres of metal music, the culture and its place in school. The main purpose of this study is to investigate the cultural behavior and lifestyle of metal. It also gives an insight of Swedish music students' habit of listening and playing metal music. The area of this study is the music education of the upper secondary school. The background chapter consists of main metal genres, the downside of Norwegian black metal, the meaning of identity amongst children and the lifestyle of metal. Both qualitative and quantitative methods were used in this study. Students from two schools answered a survey and two teachers participated in the interviews. The result shows an interest in metal music among most the of the participants in the survey. It also indicates that there is an interest for playing metal music in school. One of the informants also believes that there might be a need of teachers with musical competence from the metal genres

SIRT6 polymorphism rs117385980 is associated with longevity and healthy aging in Finnish men

Background: Sirtuin-6 (SIRT6) is involved in various crucial cellular pathways, being a key regulator of telomere structure, DNA repair, metabolism, transcriptional control and the NF-kappa B pathway. Sirt6 knock-out mice have been reported to develop typical features of aging and senescence at the age of 2-3 weeks and die within 4 weeks. The aim of this study was to investigate whether sequence variations of SIRT6 are associated with aging and longevity in Finnish men. Methods: The sample of this study consisted of 43 longer-living and healthy males and 92 male control subjects who have died of natural causes at an average age of 66,6 (+/- 4,1) years and who belonged to the Helsinki Birth Cohort Study (HBCS). Single nucleotide polymorphisms (SNPs) in the exons and their surroundings of the SIRT6 were studied using direct PCR sequencing. Results: The SNP rs117385980 (C > T), situated 23 bases downstream of the exon 2 exon/intron border was found in heterozygous form in 1/43 longer-living healthy men (Minor allele frequency (MAF) 0,0116) and in 9/92 controls (MAF 0,0489). To replicate this finding, we studied a group of 63 healthy men at an average age of 83 years from the Helsinki Businessmen Study (HBS)-cohort. The heterozygosity of the same SNP was seen in 2/63 men from the HBS-cohort (MAF 0,0159). Fisher exact test was performed in our two combined study samples. The P-value for all samples combined was 0.07 and the odds ratio 3.53 (95% confidence interval 0.96-13.4). Conclusions: These results suggest an inverse association between the T allele of rs117385980 and longevity. The result needs to be confirmed in a larger study. It remains to be determined whether rs117385980 itself has an effect or if it is a mere genetic marker for some other yet undiscovered sequence variant causing a functional effect.Peer reviewe

Polygenic Risk Score of SERPINA6/SERPINA1 Associates with Diurnal and Stress-Induced HPA Axis Activity in Children

Purpose: Corticosteroid-binding globulin (CBG) transports glucocorticoids in blood. Variation in genes SERPINA6 encoding for CBG, SERPINA2 and SERPINAI (serpin family A member 6, 2, and 1) have been shown to influence morning plasma cortisol and CBG in adults. However, association of this genetic variation with diurnal and stress-induced salivary cortisol remain unknown. This study aims to investigate the effect of genetic variation in SERPINA6/2/1 loci on diurnal and stress-induced salivary cortisol in children. Methods: We studied 186, 8-year-old children with genome-wide genotyping. We generated weighted polygenic risk score (PRS) based on 6 genome-wide significant SNPs (rs11621961, rs11629171, rs7161521, rs2749527, rs3762132, rs4900229) derived from the CORNET meta-analyses. Salivary cortisol was measured across one day and in response to the Trier Social Stress Test for Children (TSST-C). Results: Mixed models, adjusted for covariates, showed that the PRS x sampling time interactions associated with diurnal (P <0.001) and stress-induced (P = 0.009) salivary cortisol. In the high PRS group (dichotomized at median) the diurnal salivary cortisol pattern decreased less from awakening to bedtime than in the low PRS group (standardized estimates of sampling time -0.64 vs. -0.73, P <0.0001 for both estimates). In response to stress, salivary cortisol increased in the high PRS group while it remained unchanged in the low PRS group (standardized estimates of sampling time 0.12, P = 0.015 vs. -0.06, P = 0.16). These results were mainly driven by minor alleles of rs7161521 (SERPINA6) and rs4900229 (SERPINAI). Conclusions: Genetic variation in SERPINA6/2/1loci may underpin higher hypothalamic-pituitary-adrenocortical axis activity in children.Peer reviewe

Heterozygous TYROBP deletion (PLOSLFIN) is not a strong risk factor for cognitive impairment

Biallelic loss-of-function mutations in TYROBP and TREM2 cause a rare disease that resembles early-onset frontotemporal dementia with bone lesions called polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). Some PLOSL-causing variants in TREM2 have also been associated with Alzheimer's disease when heterozygous. Here, we studied the PLOSLFIN TYROBP deletion that covers 4 of the gene's 5 exons. We genotyped 3220 older Finns (mean age 79, range 58-104) and found 11 deletion carriers (mean age 78, range 60-94). The carrier prevalence was 0.0034 (1 in 293) that matches previous findings in younger cohorts suggesting no significant early mortality. By comparing Mini-Mental State Examination (MMSE) scores and diagnoses of dementia, we did not find any significant differences between TYROBP deletion carriers and noncarriers (all p-values >0.5). Neuropathological analysis of 2 deletion carriers (aged 89 and 94 years) demonstrated only minimal beta amyloid pathology (Consortium to Establish a Registry for Alzheimer's Disease (CERAD) score 0). Collectively these results suggest that heterozygous carriership of the TYROBP deletion is not a major risk factor of cognitive impairment. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

C9orf72 hexanucleotide repeat allele tagging SNPs : Associations with ALS risk and longevity

Peer reviewe

C9orf72 hexanucleotide repeat length in older population: normal variation and effects on cognition

The hexanucleotide repeat expansion in C9orf72 is a common cause of amyotrophic lateral sclerosis/frontotemporal dementia and also rarely found in other psychiatric and neurodegenerative conditions. Alleles with >30 repeats are often considered an expansion, but the pathogenic repeat length threshold is still unclear. It is also unclear whether intermediate repeat length alleles (often defined either as 7-30 or 20-30 repeats) have clinically significant effects. We determined the C9orf72 repeat length distribution in 3142 older Finns (aged 60-104 years). The longest nonexpanded allele was 45 repeats. We found 7-45 repeats in 1036/3142 (33%) individuals, 20-45 repeats in 56/3142 (1.8%), 30-45 repeats in 12/3142 (0.38%), and expansion (>45 repeats) in 6/3142 (0.19%). There was no apparent clustering of neurodegenerative or psychiatric diseases in individuals with 30-45 repeats indicating that 30-45 repeats are not pathogenic. None of the 6 expansion carriers had a diagnosis of amyotrophic lateral sclerosis/frontotemporal dementia but 4 had a diagnosis of a neurodegenerative or psychiatric disease. Intermediate length alleles (categorized as 7-45 and 20-45 repeats) did not associate with Alzheimer's disease or cognitive impairment. (C) 2019 The Author(s). Published by Elsevier Inc.Peer reviewe

Carriership of two copies of C9orf72 hexanucleotide repeat intermediate-length alleles is a risk factor for ALS in the Finnish population

The hexanucleotide repeat expansion in intron 1 of the C9orf72 gene causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. In addition to the effects of the pathogenic expansion, a role of intermediate-length alleles has been suggested in ALS, corticobasal degeneration and Parkinson's disease. Due to the rarity of intermediate-length alleles with over 20 repeats and the geographical variability in their frequency, large studies that account for population stratification are needed to elucidate their effects. To this aim, we used repeat-primed PCR and confirmatory PCR assays to determine the C9orf72 repeat allele lengths in 705 ALS patients and 3958 controls from Finland. After exclusion of expansion carriers (25.5% of the ALS patients and 0.2% of the controls), we compared the frequency of intermediate-length allele carriers of 525 ALS cases and 3950 controls using several intermediate-length allele thresholds (7-45, 17-45, 21-45, 24-45 and 24-30). The carriership of an intermediate-length allele did not associate with ALS (Fisher's test, all p >= 0.15) nor was there any association with survival (p >= 0.33), when we divided our control group into three age groups (18-65, 66-84 and 85-105 years). Carriership of two intermediate-length alleles was associated with ALS, when the longer allele was >= 17 repeats (p=0.002, OR 5.32 95% CI 2.02-14.05) or >= 21 repeats (p=0.00016, OR 15.21 95% CI 3.79-61.0). Our results show that intermediate-length alleles are a risk factor of ALS when present in both alleles, whereas carrying just one intermediate-length allele was not associated with ALS or survival.Peer reviewe

Mice Chronically Fed High-Fat Diet Have Increased Mortality and Disturbed Immune Response in Sepsis

BACKGROUND: Sepsis is a potentially deadly disease that often is caused by gram-positive bacteria, in particular Staphylococcus aureus (S. aureus). As there are few effective therapies for sepsis, increased basic knowledge about factors predisposing is needed. METHODOLOGY/PRINCIPAL FINDINGS: The purpose of this study was to study the effect of Western diet on mortality induced by intravenous S. aureus inoculation and the immune functions before and after bacterial inoculation. Here we show that C57Bl/6 mice on high-fat diet (HFD) for 8 weeks, like genetically obese Ob/Ob mice on low-fat diet (LFD), have increased mortality during S. aureus-induced sepsis compared with LFD-fed C57Bl/6 controls. Bacterial load in the kidneys 5-7 days after inoculation was increased 10-fold in HFD-fed compared with LFD-fed mice. At that time, HFD-fed mice had increased serum levels and fat mRNA expression of the immune suppressing cytokines interleukin-1 receptor antagonist (IL-1Ra) and IL-10 compared with LFD-fed mice. In addition, HFD-fed mice had increased serum levels of the pro-inflammatory IL-1beta. Also, HFD-fed mice with and without infection had increased levels of macrophages in fat. The proportion and function of phagocytosing granulocytes, and the production of reactive oxygen species (ROS) by peritoneal lavage cells were decreased in HFD-fed compared with LFD-fed mice. CONCLUSIONS: Our findings imply that chronic HFD disturb several innate immune functions in mice, and impairs the ability to clear S. aureus and survive sepsis

Mid-Holocene European climate revisited: New high-resolution regional climate model simulations using pollen-based land-cover

Land-cover changes have a clear impact on local climates via biophysical effects. European land cover has been affected by human activities for at least 6000 years, but possibly longer. It is thus highly probable that humans altered climate before the industrial revolution (AD1750-1850). In this study, climate and vegetation 6000 years (6 ka) ago is investigated using one global climate model, two regional climate models, one dynamical vegetation model, pollen-based reconstruction of past vegetation cover using a model of the pollen-vegetation relationship and a statistical model for spatial interpolation of the reconstructed land cover. This approach enables us to study 6 ka climate with potential natural and reconstructed land cover, and to determine how differences in land cover impact upon simulated climate. The use of two regional climate models enables us to discuss the robustness of the results. This is the first experiment with two regional climate models of simulated palaeo-climate based on regional climate models.Different estimates of 6 ka vegetation are constructed: simulated potential vegetation and reconstructed vegetation. Potential vegetation is the natural climate-induced vegetation as simulated by a dynamical vegetation model driven by climate conditions from a climate model. Bayesian spatial model interpolated point estimates of pollen-based plant abundances combined with estimates of climate-induced potential un-vegetated land cover were used for reconstructed vegetation. The simulated potential vegetation is heavily dominated by forests: evergreen coniferous forests dominate in northern and eastern Europe, while deciduous broadleaved forests dominate central and western Europe. In contrast, the reconstructed vegetation cover has a large component of open land in most of Europe.The simulated 6 ka climate using reconstructed vegetation was 0-5 degrees C warmer than the pre-industrial (PI) climate, depending on season and region. The largest differences are seen in north-eastern Europe in winter with about 4-6 degrees C, and the smallest differences (close to zero) in southwestern Europe in winter. The simulated 6 ka climate had 10-20% more precipitation than PI climate in northern Europe and 10-20% less precipitation in southern Europe in summer. The results are in reasonable agreement with proxy-based climate reconstructions and previous similar climate modelling studies. As expected, the global model and regional models indicate relatively similar climates albeit with regional differences indicating that, models response to land-cover changes differently.The results indicate that the anthropogenic land-cover changes, as given by the reconstructed vegetation, in this study are large enough to have a significant impact on climate. It is likely that anthropogenic impact on European climate via land-use change was already taking place at 6 ka. Our results suggest that anthropogenic land-cover changes at 6 ka lead to around 0.5 degrees C warmer in southern Europe in summer due to biogeophysical forcing. (C) 2022 The Authors. Published by Elsevier Ltd