| 1. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 2. |
- Hanzén, Sarah, et al.
(författare)
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Lifespan Control by Redox-Dependent Recruitment of Chaperones to Misfolded Proteins
- 2016
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Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 166:1, s. 140-151
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Tidskriftsartikel (refereegranskat)abstract
- Caloric restriction (CR) extends the lifespan of flies, worms, and yeast by counteracting age-related oxidation of H2O2-scavenging peroxiredoxins (Prxs). Here, we show that increased dosage of the major cytosolic Prx in yeast, Tsa1, extends lifespan in an Hsp70 chaperone-dependent and CR-independent manner without increasing H2O2 scavenging or genome stability. We found that Tsa1 and Hsp70 physically interact and that hyperoxidation of Tsa1 by H2O2 is required for the recruitment of the Hsp70 chaperones and the Hsp104 disaggregase to misfolded and aggregated proteins during aging, but not heat stress. Tsa1 counteracted the accumulation of ubiquitinated aggregates during aging and the reduction of hyperoxidized Tsa1 by sulfiredoxin facilitated clearance of H2O2-generated aggregates. The data reveal a conceptually new role for H2O2 signaling in proteostasis and lifespan control and shed new light on the selective benefits endowed to eukaryotic peroxiredoxins by their reversible hyperoxidation.
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| 3. |
- Josefson, Rebecca, et al.
(författare)
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How and why do toxic conformers of aberrant proteins accumulate during ageing?
- 2017
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Ingår i: Essays in Biochemistry. - 0071-1365. ; 61:3, s. 317-324
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Tidskriftsartikel (refereegranskat)abstract
- Ageing can be defined as a gradual decline in cellular and physical functions accompanied by an increased sensitivity to the environment and risk of death. The increased risk of mortality is causally connected to a gradual, intracellular accumulation of so-called ageing factors, of which damaged and aggregated proteins are believed to be one. Such aggregated proteins also contribute to several age-related neurodegenerative disorders e.g. Alzheimer's, Parkinson's, and Huntington's diseases, highlighting the importance of protein quality control (PQC) in ageing and its associated diseases. PQC consists of two interrelated systems: the temporal control system aimed at refolding, repairing, and/or removing aberrant proteins and their aggregates and the spatial control system aimed at harnessing the potential toxicity of aberrant proteins by sequestering them at specific cellular locations. The accumulation of toxic conformers of aberrant proteins during ageing is often declared to be a consequence of an incapacitated temporal PQC system-i.e. a gradual decline in the activity of chaperones and proteases. Here, we review the current knowledge on PQC in relation to ageing and highlight that the breakdown of both temporal and spatial PQC may contribute to ageing and thus comprise potential targets for therapeutic interventions of the ageing process. © 2017 The Author(s).
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| 4. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 5. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 6. |
- Allen-Perkins, Alfonso, et al.
(författare)
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CropPol : a dynamic, open and global database on crop pollination
- 2022
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Ingår i: Ecology. - : Wiley. - 0012-9658 .- 1939-9170. ; 103:3
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Tidskriftsartikel (refereegranskat)abstract
- Seventy five percent of the world's food crops benefit from insect pollination. Hence, there has been increased interest in how global change drivers impact this critical ecosystem service. Because standardized data on crop pollination are rarely available, we are limited in our capacity to understand the variation in pollination benefits to crop yield, as well as to anticipate changes in this service, develop predictions, and inform management actions. Here, we present CropPol, a dynamic, open and global database on crop pollination. It contains measurements recorded from 202 crop studies, covering 3,394 field observations, 2,552 yield measurements (i.e. berry weight, number of fruits and kg per hectare, among others), and 47,752 insect records from 48 commercial crops distributed around the globe. CropPol comprises 32 of the 87 leading global crops and commodities that are pollinator dependent. Malus domestica is the most represented crop (32 studies), followed by Brassica napus (22 studies), Vaccinium corymbosum (13 studies), and Citrullus lanatus (12 studies). The most abundant pollinator guilds recorded are honey bees (34.22% counts), bumblebees (19.19%), flies other than Syrphidae and Bombyliidae (13.18%), other wild bees (13.13%), beetles (10.97%), Syrphidae (4.87%), and Bombyliidae (0.05%). Locations comprise 34 countries distributed among Europe (76 studies), Northern America (60), Latin America and the Caribbean (29), Asia (20), Oceania (10), and Africa (7). Sampling spans three decades and is concentrated on 2001-05 (21 studies), 2006-10 (40), 2011-15 (88), and 2016-20 (50). This is the most comprehensive open global data set on measurements of crop flower visitors, crop pollinators and pollination to date, and we encourage researchers to add more datasets to this database in the future. This data set is released for non-commercial use only. Credits should be given to this paper (i.e., proper citation), and the products generated with this database should be shared under the same license terms (CC BY-NC-SA). This article is protected by copyright. All rights reserved.
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| 7. |
- Andersson, August, et al.
(författare)
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(14)C-Based source assessment of soot aerosols in Stockholm and the Swedish EMEP-Aspvreten regional background site
- 2011
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310 .- 1873-2844. ; 45:1, s. 215-222
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Tidskriftsartikel (refereegranskat)abstract
- Combustion-derived soot or black carbon (BC) in the atmosphere has a strong influence on both climate and human health. In order to propose effective mitigation strategies for BC emissions it is of importance to investigate geographical distributions and seasonal variations of BC emission sources. Here, a radiocarbon methodology is used to distinguish between fossil fuel and biomass burning sources of soot carbon (SC). SC is isolated for subsequent off-line (14)C quantification with the chemothermal oxidation method at 375 degrees C (CTO-375 method), which reflects a recalcitrant portion of the BC continuum known to minimize inadvertent inclusion of any non-pyrogenic organic matter. Monitored wind directions largely excluded impact from the Stockholm metropolitan region at the EMEP-Aspvreten rural station 70 km to the south-west. Nevertheless, the Stockholm city and the rural stations yielded similar relative source contributions with fraction biomass (f(biomass)) for fall and winter periods in the range of one-third to half. Large temporal variations in (14)C-based source apportionment was noted for both the 6 week fall and the 4 month winter observations. The f(biomass) appeared to be related to the SC concentration suggesting that periods of elevated BC levels may be caused by increased wood fuel combustion. These results for the largest metropolitan area in Scandinavia combine with other recent (14)C-based studies of combustion-derived aerosol fractions to suggest that biofuel combustion is contributing a large portion of the BC load to the northern European atmosphere.
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| 8. |
- Andersson, Felicia, et al.
(författare)
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Resedagbok England/Wales - Arkitektur & teknik 2018
- 2018
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Denna resedagbok är en del av Arkitektur och teknik- studenternas förberedelse för årskurs 3 och särskilt en träning i att söka, upptäcka och iakkta arkitekturens komplexa sammanhang och de värden som kan skapas genom arkitektur. Under studieresan byggs ett grundmaterial till dagboken upp genom förberedda presentationer, gemensamma analyser, undersökande skisser och konstnärliga övningar. Studieresan följs upp och bearbetas vid seminarier och genom korsläsning av texter där studenterna uppmanas till ett personligt reflekterande hållningssätt. På så sätt blir dagboken ett levande dokument som visar vår glädje och nyfikenhet över de många broar och byggnader vi upplevt tillsammans, och ett dokument som vill locka oss och alla läsare till vidare upptäcktsfärder.
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| 9. |
- Andersson Granberg, Tobias, et al.
(författare)
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Tåla : Trygghetsskapande åtgärder för landsbygden
- 2010
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I april 2010 gav regeringen i uppdrag till Myndigheten för samhällsskydd och beredskap (MSB) att i ett projekt öka säkerheten på landsbygden genom nya former för räddning och respons. Inom ramen för ovanstående uppdrag, vilket benämns ”Samhällsviktig samverkan i landsbygd” har CARER – Centrum för respons- och räddningssystem – vid Linköpings universitet fått i uppdrag av MSB att inventera vilka behov och resurser för säkerhet och trygghet som existerar på lands- och glesbygd, samt undersöka vilka andra projekt och initiativ som föregått detta, nationellt och internationellt. CARERs projekt, som görs inom ramen för regeringsuppdraget, benämns Trygghetshöjande åtgärder för landsbygden (TÅLA).TÅLA har genomförts som fyra sammanhängande delstudier där de två första delstudierna använder kvalitativ metodik, främst intervjuer, och syftar till att skapa en förståelse för den upplevda tryggheten på lands- och glesbygden, samt utröna vad den består i och hur den kan stärkas. Delstudie 3 syftar till att kvantitativt uttrycka behov och resurser för säkerhet och trygghet på landsoch glesbygd genom ett urval av indikatorer. Delstudie 4 syftar till att ge en överblick över tidigare forskning och utveckling på området.Några generella slutsatser som kan dras från TÅLA-projektets olika delstudier är att det finns en god medvetenhet hos boende i land- och glesbygd för att det kan ta tid innan hjälp kan fås ifrån de traditionella räddningssystemen (som till exempel polis eller räddningstjänst), ett faktum som också kan bekräftas numerärt. Vissa indikatorer tyder dessutom på att boende på lands- och glesbygden är mer drabbade av olyckor än boende i tätort, vilket ger ett ökat behov av de aktuella resurserna. Detta har lett till att nya typer av lösningar har utvecklats, oftast av de boende, för att bistå vid olyckor, många baserade på självhjälp och frivillighet.Tydligt är också att trygghet omfattar mer än bara blåljusverksamheter och stöd från det allmänna. Här inkluderas också behov som el, vatten och möjligheten att handla mat. En stor del av den upplevda tryggheten hos befolkningen kommer från det sociala nätverk som finns i respektive by. Möjligheter till kommunikation är centralt och det är när individen är ensam utan möjlighet till kontakt med omvärlden som den största otryggheten infinner sig.Det framkom under projektet flera exempel på samverkan och de som medverkar framhåller vikten av att känna varandra innan insatsen, för att bästa möjliga resultat ska uppnås. Såväl de båda kvalitativa studierna som kunskapsöversikten pekar på att en trolig väg till framgång för en ökad säkerhet och trygghet på landsbygden bygger på att de lokala resurserna och strukturerna nyttjas i samverkan med de traditionella räddningsresurserna. Detta innebär att det bör vara möjligt att stärka dels de boendes möjligheter att hjälpa sig själva och att hjälpa varandra, men också att nyttja organisationer som idag inte tillhör blåljusmyndigheterna för att i samverkan med räddningstjänsten, sjukvården och polisen kunna bistå vid olyckor, akuta sjukdomsförlopp och andra relevanta händelser. Viktigt att beakta i detta sammanhang är då att använda de befintliga strukturer som existerar bland såväl boende som olika organisationer, för att på bästa sätt kunna dra nytta av den lokala kunskap, de resurser och det engagemang som existerar.
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| 10. |
- Andersson, Jan, et al.
(författare)
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Aktiebolagsrätt
- 1995
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Ingår i: Kunskapsföretaget i ett rättsligt perspektiv. - Stockholm : Fritze. - 9138502267
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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