| 1. |
- Williamson, Alice, et al.
(författare)
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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
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Tidskriftsartikel (refereegranskat)abstract
- Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
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| 2. |
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| 3. |
- Alfredsson, Lars, et al.
(författare)
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Job strain and major risk factors for coronary heart disease. : Baseline results from the WOLF Study
- 2002
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Ingår i: Scandinavian Journal of Work, Environment & Health. - 0355-3140. ; 28:4, s. 238-248
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Tidskriftsartikel (refereegranskat)abstract
- The results do not support the hypothesis that job strain has an adverse impact on serum total cholesterol and plasma fibrinogen levels. They suggest that an increased risk of coronary heart disease in association with job strain, if causal, is mediated by other factors, possibly partly by hypertension and low levels of high-density lipoprotein cholesterol.
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| 4. |
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| 5. |
- Andersson, Mathias H, et al.
(författare)
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A framework for regulating underwater noise during pile driving
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Pile driving is a common technique used during the construction of bridges, offshore wind power, and underwater infrastructure or shoreline structures. It is the process by which a foundation, beam or pole is hammered or vibrated down into the bottom, which can generate extremely loud noise that propagates throughout the surrounding water and sediment. The noise can reach such high levels that marine animals are at risk of disturbance, injury or even death.Sweden currently lacks established thresholds stating the level at which underwater noise potentially disturbs or injures marine animals. Hence, there are no guidance values for allowable underwater noise levels from noiseproducing activities to avoid serious environmental impacts. Several countries in Europe have defined thresholds for when underwater noise can result in severe negative environmental impacts as well as standards for measuring, analysing and reporting underwater noise levels.The purpose of this study is to review the scientific literature on underwater noise from pile driving and its effects on marine life. The study aims to define the noise levels that can cause injury and other negative effects and, on this basis, recommend noise levels that can be used to establish guidance values for regulating underwater noise for Swedish waters and species. The study presents examples of the factors that contribute to sound propagation in Swedish waters and how this influences the noise level from a pile strike as a function of distance at four study areas along the Swedish coast. Additionally, the study contains a thorough technical description of pile driving activities, basic underwater acoustics and noise effects on marine animals. These effects (injury and behavioral, e.g., flight, but not subtle effects) are demonstrated on representative species such as the harbour porpoise (Phocoena phocoena), Atlantic cod (Gadus morhua), Atlantic herring (Clupea harengus) and on fish larvae and eggs. The study’s authors look atthe original sources of information that other countries base their guidelines and thresholds on, so the recommendations follow scientifically determined levels rather than values that have been rounded off or otherwise altered.The study presents sound levels in three different units, each with different biological relevance to the effects caused by a pile driving activity. None of the sound levels have been frequency weighted for a specific species, as this method is not yet fully established. The first unit used is the sound pressure level SPL(peak), which is the maximum overpressure or underpressure of the noise pulse generated by the pile strike. This unit has a high relevance for behavioural effects. The sound exposure level, SEL, is the calculated energy level over a period of time and expresses the energy of the entire sound pulse. SEL is the unit most related to hearing impairing effects. SEL(ss) is the value for a single strike while SEL(cum) is the cumulative value of a determined number of pulses over a period of time. The review revealed that for Atlantic cod and Atlantic herring there are currently no studies that can be used to determine a species’ specific threshold value for injury, but studies show that loud noise can affect both species negatively. Because of this, the recommended noise levels for injury are based mainly on studies on other species exposed to pile driving noise in laboratory environments, supported by studies conducting large-scale experiments in tanks and oceans. The levels at which fish are at risk of death or sustaining serious injury to internal organs is SPL 207 dB re 1 μPa, SEL(ss) 174 dB re 1 μPa2s and SEL(cum) 204 dB re 1 μPa2s. Note that for injury in fish, the cumulative sound exposure level has higher relevance than the single-strike level as the cited studies found injuries after a certain time period of exposure. The thresholds for fish larvae and eggs are based on the fact that no negative effects were observed at exposures of up to SPL(peak) 217 dB re 1 μPa, SEL(ss) 187 dB re 1 μPa2s and SEL(cum) 207 dB re 1 μPa2s. However, there are relatively few studies on early life stages of fish. There are more species-specific studies on harbour porpoises regarding noise than there are for Atlantic cod and Atlantic herring. Nonetheless, only a few can be used to determine thresholds that will lead to injury or negative behavioural effects. The levels at which there is a risk of a temporary impact on hearing, i.e. temporary threshold shift (TTS), for the harbour porpoises is SPL(peak) 194 dB re 1 μPa, SEL(ss) 164 dB re 1 μPa2s and SEL(cum) 175 dB re 1 μPa2s. When it comes to TTS, the cumulative sound exposure level, SEL(cum), is of primary importance. However, this unit is dependent on a specific time and number of pulses. For permanent threshold shift (PTS), the level is set to SPL(peak) 200 dB re 1 μPa, SEL(ss) 179 dB re 1 μPa2s and SEL(cum) 190 dB re 1 μPa2s. The recommended level should be revised as new relevant studies are conducted.
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| 6. |
- Andersson, Mathias H., et al.
(författare)
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Underlag för reglering av undervattensljud vid pålning
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Vid byggnation av broar, havsbaserad vindkraft och andra havsbaserade eller strandnära konstruktioner används det oftast någon form av pålningsteknik för att få ner konstruktionen i botten. Detta innebär att ett fundament, balk eller spont hamras eller vibreras ner i botten, vilket kan generera mycket höga ljudnivåer som sprids ut i vattnet och ner i botten. Ljudnivåerna är så höga att marina organismer kan störas, skadas eller till och med dödas. Idag saknar Sverige fastställda ljudnivåer för när undervattensbuller blir så högt att de kan skada djur i havet. Det saknas därför också vedertagna begränsningsvärden som anger vilka nivåer av undervattensbuller som kan tillåtas för bullrande aktiviteter utan att riskera allvarliga miljöeffekter. Flera länder i Europa har någon form av gränsvärden för när bullernivån under vattnet kan ge upphov till allvarlig miljöpåverkan liksom standarder för hur undervattensbuller skall mätas och rapporteras. Syftet med denna studie var att ta fram ett vetenskapligt underlag rörande ljudet från pålning i havet och dess påverkan på det marina livet. Slutmålet var att utifrån den vetenskapliga information som finns idag ge förslag på ljudnivåer för skador och negativ påverkan som sedan kan användas för att ta fram begränsningsvärden för reglering av undervattensbuller anpassade för svenska vatten och arter. Studien ger ett antal exempel på vilka faktorer som påverkar ljudutbredningen i svenska vatten och hur detta påverkar ett pålningsslags ljudnivå som funktion av avstånd i fyra typområden kring den svenska kusten. Vidare presenteras ingående både tekniska beskrivningar av pålningsaktiviteter, undervattensakustik samt påverkan på marina djur. Denna påverkan (skada och flyktbeteende men ej subtila effekter) demonstreras med hjälp av ett antal typarter som tandvalen tumlare (Phocoena phocoena) och fiskarterna torsk (Gadus morhua) och sill (Clupea clupea) samt fiskägg och fisklarver. I denna studie har författarna gått tillbaka till de originalkällor av information som andra länders gränsvärden grundas på, så att rekommendationerna bygger på vetenskapliga nivåer och inte värden som har avrundats eller på annat sätt ändrats.Studien presenterar ljudnivåer i tre olika enheter då dessa har olika biologisk relevans för påverkan från en pålningsaktivitet. Inga av dessa värden har frekvensviktats för att anpassas för en specifik art då denna metod ännu inte är helt vedertagen. Den första enheten är ljudtrycksnivå SPL(topp), d.v.s. det maximala över- eller undertryck som den av pålningsslaget genererade ljudpulsen har. Denna enhet har hög relevans för beteendepåverkan. För ljudexponeringsnivå SEL, beräknas ljudnivån över en viss tid och tar då med energin i hela ljudpulsen. SEL är den enhet som visats vara bäst relaterad till hörselskador. SEL(enkel) är värdet för en enkel puls och för det kumulativa SEL(kum) har antalet pulser under en viss tid summerats.Litteraturstudien på torsk och sill visar att det i dagsläget inte finns några studier som kan användas för att fastställa en artspecifik ljudnivå för skada men litteraturen visar tydligt på att höga bullernivåer kan påverka torsk och sill negativt. Istället baseras de föreslagna nivåerna i huvudsak på studier på andra arter som har exponerats för pålningsljud i laboratoriemiljö med stöd av studier från mer storskaliga experiment i tankar och hav. De nivåer då fisk riskerar att dödas eller få allvarliga skador på inre organ är 207 dB re 1 μPa SPL(topp), 174 dB re 1 μPa2s SEL(enkel) och 204 dB re 1 μPa2s SEL(kum). Notera att för skada på fisk har det kumulativa värdet högre relevans än enkelvärdet för SEL eftersom studier visar att skador uppkommer efter en viss tids exponering. Nivåerna för påverkan på fiskägg och larver grundas i att inga negativa effekter har observerats vid exponering för ljudtryck från pålning upp till 217 dB re 1 μPa SPL(topp), 187 dB re 1 μPa2s SEL(enkel) och 207 dB re 1 μPa2s SEL(kum). Det finns emellertid mycket få studier relaterat till pålningsljud för dessa livsstadier. För tumlare finns det fler artspecifika studier gjorda relaterat till buller än för torsk och sill. Det är dock endast ett fåtal som kan användas för att bestämma ljudnivåer som leder till skada eller negativ beteendepåverkan. De ljudnivåer som riskerar ge tillfällig hörselnedsättning (TTS) hos tumlare är 194 dB re 1 μPa SPL(topp), 164 dB re 1 μPa2s SEL(enkel) och 175 dB re 1 μPa2s SEL(kum). Det är framförallt den kumulativa ljudexponeringsnivån SEL(kum) som har stor betydelse för just TTS, dock hänger detta värde ihop med en specifik tid och antalet pulser vilket kan vara svårt att uppskatta i förväg. Vidare avseende permanent hörselskada (PTS) är ljudnivån 200 dB re 1 μPa SPL(topp), 179 dB re 1 μPa2s SEL(enkel) och 190 dB re 1 μPa2s SEL(kum). Föreslagna nivåer bör uppdateras när nya relevanta forskningsstudier tillkommer.
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| 7. |
- Baldanzi, Gabriel, et al.
(författare)
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Accelerometer-based physical activity is associated with the gut microbiota in 8416 individuals in SCAPIS.
- 2024
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 100
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous population-based studies investigating the relationship between physical activity and the gut microbiota have relied on self-reported activity, prone to reporting bias. Here, we investigated the associations of accelerometer-based sedentary (SED), moderate-intensity (MPA), and vigorous-intensity (VPA) physical activity with the gut microbiota using cross-sectional data from the Swedish CArdioPulmonary bioImage Study.METHODS: In 8416 participants aged 50-65, time in SED, MPA, and VPA were estimated with hip-worn accelerometer. Gut microbiota was profiled using shotgun metagenomics of faecal samples. We applied multivariable regression models, adjusting for sociodemographic, lifestyle, and technical covariates, and accounted for multiple testing.FINDINGS: Overall, associations between time in SED and microbiota species abundance were in opposite direction to those for MPA or VPA. For example, MPA was associated with lower, while SED with higher abundance of Escherichia coli. MPA and VPA were associated with higher abundance of the butyrate-producers Faecalibacterium prausnitzii and Roseburia spp. We observed discrepancies between specific VPA and MPA associations, such as a positive association between MPA and Prevotella copri, while no association was detected for VPA. Additionally, SED, MPA and VPA were associated with the functional potential of the microbiome. For instance, MPA was associated with higher capacity for acetate synthesis and SED with lower carbohydrate degradation capacity.INTERPRETATION: Our findings suggest that sedentary and physical activity are associated with a similar set of gut microbiota species but in opposite directions. Furthermore, the intensity of physical activity may have specific effects on certain gut microbiota species.FUNDING: European Research Council, Swedish Heart-Lung Foundation, Swedish Research Council, Knut and Alice Wallenberg Foundation.
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| 8. |
- Boström, A., et al.
(författare)
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Risk factors for acute and overuse sport injuries in Swedish children 11 to 15 years old : What about resistance training with weights?
- 2016
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 26:3, s. 317-323
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Tidskriftsartikel (refereegranskat)abstract
- To determine the 1-year self-reported incidence of overuse and traumatic sport injuries and risk factors for injuries in children participating in a summer sports camp representing seven different sports. 4363 children, 11 to 15 years old participating in a summer camp in seven different sports answered a questionnaire. Injury in this cross-sectional study was defined as a sport-related trauma or overload leading to pain and dysfunction preventing the person from participation in training or competition for at least 1 week. A number of risk factors for injury were investigated such as sex, age, number of hours spent on training in general, and on resistance training with weights. Nearly half [49%, 95% confidence interval (CI) 48–51%] of the participants had been injured as a result of participation in a sport during the preceding year, significantly more boys than girls (53%, 95% CI 50–55% vs 46%, 95% CI 43–48%; P < 0.001). Three factors contributed to increased incidence of sport injuries: age, sex, and resistance training with weights. Time spent on resistance training with weights was significantly associated with sport injuries in a logistic regression analysis. In children age 11 to 15 years, the risk of having a sport-related injury increased with age and occurred more often in boys than in girls. Weight training was the only modifiable risk factor that contributed to a significant increase in the incidence of sport injuries.
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| 9. |
- Broadaway, K Alaine, et al.
(författare)
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Loci for insulin processing and secretion provide insight into type 2 diabetes risk.
- 2023
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Ingår i: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299
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Tidskriftsartikel (refereegranskat)abstract
- Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.
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| 10. |
- Eliasson, Pernilla, et al.
(författare)
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Hypoxia mediates low cell-cycle activity and increases the proportion of long-term reconstituting hematopoietic stem cells during in vitro culture
- 2010
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Ingår i: Experimental Hematology. - : Elsevier. - 0301-472X .- 1873-2399. ; 38:4, s. 301-310
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Recent evidence suggests that hematopoietic stem cells (HSCs) in the bone marrow (BM) are located in areas where the environment is hypoxic. Although previous studies have demonstrated positive effects by hypoxia, its role in HSC maintenance has not been fully elucidated, neither has the molecular mechanisms been delineated. Here, we have investigated the consequence of in vitro incubation of HSCs in hypoxia prior to transplantation and analyzed the role of hypoxia-inducible factor (HIF)-1 alpha. Materials and Methods. HSC and progenitor populations isolated from mouse BM were cultured in 20% or 1% O-2, and analyzed for effects on cell cycle, expression of cyclin-dependent kinase inhibitors genes, and reconstituting ability to lethally irradiated mice. The involvement of HIF-1 alpha was studied using methods of protein stabilization and gene silencing. Results. When long-term FLT3(-)CD34(-)Lin(-)Sca-1(+)c-Kit(+) (LSK) cells were cultured in hypoxia, cell numbers were significantly reduced in comparison to normoxia. This was due to a decrease in proliferation and more cells accumulating in G(0). Moreover, the proportion of HSCs with long-term engraftment potential was increased. Whereas expression of the cyclin-dependent kinase inhibitor genes p21(cip1), p27(Kip1), and p57(Kip2) increased in LSK cells by hypoxia, only p21(cip1) was upregulated in FLT3(-)CD34(-)LSK cells. We could demonstrate that expression of p27(KiP1) and p57(Kip2) was dependent of HIF-1 alpha. Surprisingly, overexpression of constitutively active HIF-1 alpha or treatment with the HIF stabilizer agent FG-4497 led to a reduction in HSC reconstituting ability. Conclusions. Our results imply that hypoxia, in part via HIF-1 alpha, maintains HSCs by decreasing proliferation and favoring quiescence.
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