| 3911. |
- Marklund, Matti, et al.
(författare)
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Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality : An Individual-Level Pooled Analysis of 30 Cohort Studies
- 2019
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Ingår i: Circulation. - : American Heart Association. - 0009-7322 .- 1524-4539. ; 139:21, s. 2422-2436
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Tidskriftsartikel (refereegranskat)abstract
- Background:Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.Methods:We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).Results:In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15198 incident cardiovascular events occurred among 68659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.Conclusions:In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.
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| 3912. |
- Martin, Francis, et al.
(författare)
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The genome of Laccaria bicolor provides insights into mycorrhizal symbiosis
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 452:7183, s. 7-88
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Tidskriftsartikel (refereegranskat)abstract
- Mycorrhizal symbioses -- the union of roots and soil fungi -- are universal in terrestrial ecosystems and may have been fundamental to land colonization by plants1,2. Boreal, temperate, and montane forests all depend upon ectomycorrhizae1. Identification of the primary factors that regulate symbiotic development and metabolic activity will therefore open the door to understanding the role of 2 ectomycorrhizae in plant development and physiology, allowing the full ecological significance of this symbiosis to be explored. Here, we report the genome sequence of the ectomycorrhizal basidiomycete Laccaria bicolor (Fig. 1) and highlight gene sets involved in rhizosphere colonization and symbiosis. This 65-million-base genome assembly contains ~ 20,000 predicted protein-encoding genes and a very large number of transposons and repeated sequences. We detected unexpected genomic features most notably a battery of effector-type small secreted proteins (SSP) with unknown function, several of which are only expressed in symbiotic tissues. The most highly expressed SSP accumulates in the proliferating hyphae colonizing the host root. The ectomycorrhizae-specific proteins likely play a decisive role in the establishment of the symbiosis. The unexpected observation that the genome of L. bicolor lacks carbohydrate-active enzymes involved in degradation of plant cell walls, but maintains the ability to degrade non-plant cell walls, reveals the dual saprotrophic and biotrophic lifestyle of the mycorrhizal fungus which enables it to grow within both soil and living plant roots. The predicted gene inventory of the L. bicolor genome, therefore, points to previously unknown mechanisms of symbiosis operating in biotrophic mycorrhizal fungi. The availability of this genome provides an unparalleled opportunity to develop a deeper understanding of the processes by which symbionts interact with plants within their ecosystem in order to perform vital functions in the carbon and nitrogen cycles that are fundamental to sustainable plant productivity.
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| 3913. |
- Martinez, VF, et al.
(författare)
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Neuromotor repertoires in infants exposed to maternal COVID-19 during pregnancy: a cohort study
- 2023
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 13:1, s. e069194-
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate neuromotor repertoires and developmental milestones in infants exposed to antenatal COVID-19.DesignLongitudinal cohort study.SettingHospital-based study in Los Angeles, USA and Rio de Janeiro, Brazil between March 2020 and December 2021.ParticipantsInfants born to mothers with COVID-19 during pregnancy and prepandemic control infants from the Graz University Database.InterventionsGeneral movement assessment (GMA) videos between 3 and 5 months post-term age were collected and clinical assessments/developmental milestones evaluated at 6–8 months of age. Cases were matched by gestational age, gender and post-term age to prepandemic neurotypical unexposed controls from the database.Main outcome measuresMotor Optimality Scores Revised (MOS-R) at 3–5 months. Presence of developmental delay (DD) at 6–8 months.Results239 infants were enrolled; 124 cases (83 in the USA/41 in Brazil) and 115 controls. GMA was assessed in 115 cases and 115 controls; 25% were preterm. Median MOS-R in cases was 23 (IQR 21–24, range 9–28) vs 25 (IQR 24–26, range 20–28) in controls, p<0.001. Sixteen infants (14%) had MOS-R scores <20 vs zero controls, p<0.001. At 6–8 months, 13 of 109 case infants (12%) failed to attain developmental milestones; all 115 control infants had normal development. The timing of maternal infection in pregnancy (first, second or third trimester) or COVID-19 disease severity (NIH categories asymptomatic, mild/moderate or severe/critical) was not associated with suboptimal MOS-R or DD. Maternal fever in pregnancy was associated with DD (OR 3.7; 95% CI 1.12 to 12.60) but not suboptimal MOS-R (OR 0.25; 95% CI 0.04 to 0.96).ConclusionsCompared with prepandemic controls, infants exposed to antenatal COVID-19 more frequently had suboptimal neuromotor development.
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| 3914. |
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| 3915. |
- McBrien, Owen R., et al.
(författare)
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SN2018kzr : A Rapidly Declining Transient from the Destruction of a White Dwarf
- 2019
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 885:1
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Tidskriftsartikel (refereegranskat)abstract
- We present SN2018kzr, the fastest declining supernova-like transient, second only to the kilonova, AT2017gfo. SN2018kzr is characterized by a peak magnitude of M-r & xfffd;=& xfffd;?17.98, a peak bolometric luminosity of ?1.4 & xfffd;& x5e0;10(43) erg s(?1), and a rapid decline rate of 0.48 & xfffd;& xfffd;0.03 mag day(?1) in the r band. The bolometric luminosity evolves too quickly to be explained by pure Ni-56 heating, necessitating the inclusion of an alternative powering source. Incorporating the spin-down of a magnetized neutron star adequately describes the lightcurve and we estimate a small ejecta mass of M-ej & xfffd;=& xfffd;0.10 & xfffd;& xfffd;0.05 M. Our spectral modeling suggests the ejecta is composed of intermediate mass elements including O, Si, and Mg and trace amounts of Fe-peak elements, which disfavors a binary neutron star merger. We discuss three explosion scenarios for SN2018kzr, given the low ejecta mass, intermediate mass element composition, and high likelihood of additional powering?the core collapse of an ultra-stripped progenitor, the accretion induced collapse (AIC) of a white dwarf, and the merger of a white dwarf and neutron star. The requirement for an alternative input energy source favors either the AIC with magnetar powering or a white dwarf?neutron star merger with energy from disk wind shocks.
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| 3916. |
- McCarthy, Shane, et al.
(författare)
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A reference panel of 64,976 haplotypes for genotype imputation
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1279-1283
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Tidskriftsartikel (refereegranskat)abstract
- We describe a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry. Using this resource leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies, and it can help to discover and refine causal loci. We describe remote server resources that allow researchers to carry out imputation and phasing consistently and efficiently.
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| 3917. |
- McGee, Emma E., et al.
(författare)
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Smoking, Alcohol, and Biliary Tract Cancer Risk : A Pooling Project of 26 Prospective Studies
- 2019
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Ingår i: Journal of the National Cancer Institute. - : OXFORD UNIV PRESS INC. - 0027-8874 .- 1460-2105. ; 111:12, s. 1263-1278
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Forskningsöversikt (refereegranskat)abstract
- Background: Tobacco and alcohol are well-established risk factors for numerous cancers, yet their relationship to biliary tract cancers remains unclear. Methods: We pooled data from 26 prospective studies to evaluate associations of cigarette smoking and alcohol consumption with biliary tract cancer risk. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with smoking and alcohol consumption were calculated. Random-effects meta-analysis produced summary estimates. All statistical tests were two-sided. Results: Over a period of 38 369 156 person-years of follow-up, 1391 gallbladder, 758 intrahepatic bile duct, 1208 extrahepatic bile duct, and 623 ampulla of Vater cancer cases were identified. Ever, former, and current smoking were associated with increased extrahepatic bile duct and ampulla of Vater cancers risk (eg, current vs never smokers HR = 1.69, 95% CI = 1.34 to 2.13 and 2.22, 95% CI = 1.69 to 2.92, respectively), with dose-response effects for smoking pack-years, duration, and intensity (all P-trend<.01). Current smoking and smoking intensity were also associated with intrahepatic bile duct cancer (eg, >40 cigarettes per day vs never smokers HR = 2.15, 95 % CI = 1.15 to 4.00; P-trend = .001). No convincing association was observed between smoking and gallbladder cancer. Alcohol consumption was only associated with intrahepatic bile duct cancer, with increased risk for individuals consuming five or more vs zero drinks per day (HR = 2.35, 95%CI = 1.46 to 3.78; P-trend = .04). There was evidence of statistical heterogeneity among several cancer sites, particularly between gallbladder cancer and the other biliary tract cancers. Conclusions: Smoking appears to increase the risk of developing all biliary tract cancers except gallbladder cancer. Alcohol may increase the risk of intrahepatic bile duct cancer. Findings highlight etiologic heterogeneity across the biliary tract.
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| 3918. |
- McGovern, T, et al.
(författare)
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Organic dust, causing both oxidative stress and Nrf2 activation, is phagocytized by bronchial epithelial cells
- 2019
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Ingår i: American journal of physiology. Lung cellular and molecular physiology. - : American Physiological Society. - 1522-1504 .- 1040-0605. ; 317:3, s. L305-L316
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Tidskriftsartikel (refereegranskat)abstract
- Inhalation of organic dust (OD) from swine confinement facilities leads to pulmonary inflammation, airway hyperresponsiveness, and oxidative stress. In mice, pretreatment with a hydroxyl radical scavenger prevents airway inflammation and airway hyperresponsiveness (AHR) induced by OD exposure. We sought to determine a mechanism by which OD could induce oxidative stress in bronchial epithelial cells. Human bronchial epithelial cells (BEAS-2B or NHBE) were treated with various concentrations of OD, followed by evaluation of intracellular oxidative stress using 2′,7′–dichlorofluorescein diacetate (DCFDA). After stimulation with OD, gene expression of antioxidant genes was assessed by real-time quantitative PCR followed by quantification of Nrf2 nuclear translocation using a luciferase reporter assay. Phagocytic markers (CD36 and CD68) were analyzed by FACS. Cells were treated with an actin inhibitor, cytochalasin D, before OD exposure and evaluated for Nrf2 nuclear translocation and DCFDA. Mice were pretreated with sulforaphane, the Nrf2 activator, before OD exposure and evaluated for pulmonary inflammation and airway reactivity. OD induced a time- and concentration-dependent increase in DCFDA. mRNA expression levels of Nrf2-dependent genes and Nrf2 nuclear translocation were increased after OD exposure. OD exposure increased the expression of CD68 and CD36. Cytochalasin D prevented oxidative stress and Nrf2 nuclear translocation after OD. Pretreatment with sulforaphane prevented OD-induced inflammation and AHR while increasing the uptake of OD in bronchial epithelial cells. Bronchial epithelial cells can phagocytose OD, resulting in an increase in endogenous oxidative stress. Nrf2-dependent mechanisms mediate the antioxidant response to OD.
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| 3919. |
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| 3920. |
- McMullan, G, et al.
(författare)
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Electron imaging with medipix2 hybrid pixel detector
- 2007
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Ingår i: Ultramicroscopy. - : Elsevier BV. - 0304-3991 .- 1879-2723. ; 107:4-5, s. 401-413
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Tidskriftsartikel (refereegranskat)abstract
- The electron imaging performance of Medipix2 is described. Medipix2 is a hybrid pixel detector composed of two layers. It has a sensor layer and a layer of readout electronics, in which each 55 μm×55 μm pixel has upper and lower energy discrimination and MHz rate counting. The sensor layer consists of a 300 μm slab of pixellated monolithic silicon and this is bonded to the readout chip. Experimental measurement of the detective quantum efficiency, DQE(0) at 120 keV shows that it can reach 85% independent of electron exposure, since the detector has zero noise, and the DQE(Nyquist) can reach 35% of that expected for a perfect detector (4/π2). Experimental measurement of the modulation transfer function (MTF) at Nyquist resolution for 120 keV electrons using a 60 keV lower energy threshold, yields a value that is 50% of that expected for a perfect detector (2/π). Finally, Monte Carlo simulations of electron tracks and energy deposited in adjacent pixels have been performed and used to calculate expected values for the MTF and DQE as a function of the threshold energy. The good agreement between theory and experiment allows suggestions for further improvements to be made with confidence. The present detector is already very useful for experiments that require a high DQE at very low doses.
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