| 1. |
- Sliz, E., et al.
(författare)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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| 2. |
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| 3. |
- de las Fuentes, Lisa, et al.
(författare)
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Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:6, s. 2111-2125
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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| 4. |
- Yan, C., et al.
(författare)
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Size-dependent influence of NOx on the growth rates of organic aerosol particles
- 2020
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:22
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Tidskriftsartikel (refereegranskat)abstract
- Atmospheric new-particle formation (NPF) affects climate by contributing to a large fraction of the cloud condensation nuclei (CCN). Highly oxygenated organic molecules (HOMs) drive the early particle growth and therefore substantially influence the survival of newly formed particles to CCN. Nitrogen oxide (NOx) is known to suppress the NPF driven by HOMs, but the underlying mechanism remains largely unclear. Here, we examine the response of particle growth to the changes of HOM formation caused by NOx. We show that NOx suppresses particle growth in general, but the suppression is rather nonuniform and size dependent, which can be quantitatively explained by the shifted HOM volatility after adding NOx. By illustrating how NOx affects the early growth of new particles, a critical step of CCN formation, our results help provide a refined assessment of the potential climatic effects caused by the diverse changes of NOx level in forest regions around the globe.
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| 7. |
- Bianchi, F., et al.
(författare)
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The SALTENA Experiment : Comprehensive Observations of Aerosol Sources, Formation, and Processes in the South American Andes
- 2022
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 103:2, s. E212-E229
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents an introduction to the Southern Hemisphere High Altitude Experiment on Particle Nucleation and Growth (SALTENA). This field campaign took place between December 2017 and June 2018 (wet to dry season) at Chacaltaya (CHC), a GAW (Global Atmosphere Watch) station located at 5,240 m MSL in the Bolivian Andes. Concurrent measurements were conducted at two additional sites in El Alto (4,000 m MSL) and La Paz (3,600 m MSL). The overall goal of the campaign was to identify the sources, understand the formation mechanisms and transport, and characterize the properties of aerosol at these stations. State-of-the-art instruments were brought to the station complementing the ongoing permanent GAW measurements, to allow a comprehensive description of the chemical species of anthropogenic and biogenic origin impacting the station and contributing to new particle formation. In this overview we first provide an assessment of the complex meteorology, airmass origin, and boundary layer-free troposphere interactions during the campaign using a 6-month high-resolution Weather Research and Forecasting (WRF) simulation coupled with Flexible Particle dispersion model (FLEXPART). We then show some of the research highlights from the campaign, including (i) chemical transformation processes of anthropogenic pollution while the air masses are transported to the CHC station from the metropolitan area of La Paz-El Alto, (ii) volcanic emissions as an important source of atmospheric sulfur compounds in the region, (iii) the characterization of the compounds involved in new particle formation, and (iv) the identification of long-range-transported compounds from the Pacific or the Amazon basin. We conclude the article with a presentation of future research foci. The SALTENA dataset highlights the importance of comprehensive observations in strategic high-altitude locations, especially the undersampled Southern Hemisphere.
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| 8. |
- Yang, Xin, et al.
(författare)
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Cancer risks associated with germline PALB2 pathogenic variants : An international study of 524 families
- 2020
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 38:7, s. 674-685
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 3 1022). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.
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| 9. |
- Blumenstock, T., et al.
(författare)
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Characterization and potential for reducing optical resonances in Fourier transform infrared spectrometers of the Network for the Detection of Atmospheric Composition Change (NDACC)
- 2021
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 14:2, s. 1239-1252
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Tidskriftsartikel (refereegranskat)abstract
- Although optical components in Fourier transform infrared (FTIR) spectrometers are preferably wedged, in practice, infrared spectra typically suffer from the effects of optical resonances ("channeling") affecting the retrieval of weakly absorbing gases. This study investigates the level of channeling of each FTIR spectrometer within the Network for the Detection of Atmospheric Composition Change (NDACC). Dedicated spectra were recorded by more than 20 NDACC FTIR spectrometers using a laboratory mid-infrared source and two detectors. In the indium antimonide (InSb) detector domain (1900-5000 cm-1), we found that the amplitude of the most pronounced channeling frequency amounts to 0.1 ‰ to 2.0 ‰ of the spectral background level, with a mean of (0:68±0:48) ‰ and a median of 0.60 ‰. In the mercury cadmium telluride (HgCdTe) detector domain (700-1300 cm-1), we find even stronger effects, with the largest amplitude ranging from 0.3 ‰ to 21 ‰ with a mean of (2:45±4:50) ‰ and a median of 1.2 ‰. For both detectors, the leading channeling frequencies are 0.9 and 0.11 or 0.23 cm-1 in most spectrometers. The observed spectral frequencies of 0.11 and 0.23 cm-1 correspond to the optical thickness of the beam splitter substrate. The 0.9 cm-1 channeling is caused by the air gap in between the beam splitter and compensator plate. Since the air gap is a significant source of channeling and the corresponding amplitude differs strongly between spectrometers, we propose new beam splitters with the wedge of the air gap increased to at least 0.8. We tested the insertion of spacers in a beam splitter's air gap to demonstrate that increasing the wedge of the air gap decreases the 0.9 cm-1 channeling amplitude significantly. A wedge of the air gap of 0.8 reduces the channeling amplitude by about 50 %, while a wedge of about 2 removes the 0.9 cm-1 channeling completely. This study shows the potential for reducing channeling in the FTIR spectrometers operated by the NDACC, thereby increasing the quality of recorded spectra across the network.
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