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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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- Coughlin, Michael W., et al.
(författare)
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GROWTH on S190425z : Searching Thousands of Square Degrees to Identify an Optical or Infrared Counterpart to a Binary Neutron Star Merger with the Zwicky Transient Facility and Palomar Gattini-IR
- 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
- The third observing run by LVC has brought the discovery of many compact binary coalescences. Following the detection of the first binary neutron star merger in this run (LIGO/Virgo S190425z), we performed a dedicated follow-up campaign with the Zwicky Transient Facility (ZTF) and Palomar Gattini-IR telescopes. The initial skymap of this single-detector gravitational wave (GW) trigger spanned most of the sky observable from Palomar Observatory. Covering 8000 deg(2) of the initial skymap over the next two nights, corresponding to 46% integrated probability, ZTF system achieved a depth of 21 m(AB) in g- and r-bands. Palomar Gattini-IR covered 2200 square degrees in J-band to a depth of 15.5 mag, including 32% integrated probability based on the initial skymap. The revised skymap issued the following day reduced these numbers to 21% for the ZTF and 19% for Palomar Gattini-IR. We narrowed 338,646 ZTF transient ?alerts? over the first two nights of observations to 15 candidate counterparts. Two candidates, ZTF19aarykkb and ZTF19aarzaod, were particularly compelling given that their location, distance, and age were consistent with the GW event, and their early optical light curves were photometrically consistent with that of kilonovae. These two candidates were spectroscopically classified as young core-collapse supernovae. The remaining candidates were ruled out as supernovae. Palomar Gattini-IR did not identify any viable candidates with multiple detections only after merger time. We demonstrate that even with single-detector GW events localized to thousands of square degrees, systematic kilonova discovery is feasible.
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- Dang, Wen-Zhen, et al.
(författare)
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Therapeutic effects of artesunate on lupus-prone MRL/lpr mice are dependent on T follicular helper cell differentiation and activation of JAK2-STAT3 signaling pathway
- 2019
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Ingår i: Phytomedicine. - München : Elsevier. - 0944-7113 .- 1618-095X. ; 62
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Anti-malarial drug artesunate (ART), a semi-synthetic derivative of artemisnin, has immunosuppressive effects on several autoimmune diseases, including Systemic lupus erythematosus (SLE), Rheumatoid arthritis (RA), and Colitis. However, molecular mechanisms of ART, especially on follicular helper T cells (Tfh), central players in SLE pathology, are far from clear.PURPOSE: The object for this work is to investigate the therapeutic effect of ART on lupus-prone MRL/lpr mice and its regulatory function on Tfh cells.STUDY DESIGN AND METHODS: MRL/lpr mice were used to explore therapeutic effects of ART on lupus-prone MRL/lpr mice and its regulatory functions on Tfh cells. Then, experiments of renal function were accomplished using the biochemical kits. Effects of ART on histopathology of kidneys, inflammatory factors and autoantibodies were examined using H&E staining, ELISA and real-time PCR. Flow cytometry and western blot analysis were used to examine effects of ART on Tfh differentiation and Jak2-Stat3 signaling pathway.RESULTS: Upon oral administration, ART significantly prolonged the survival of MRL/lpr mice, ameliorated the lupus nephritis symptoms, decreased the levels of anti-dsDNA antibodies deposited in the kidney, and the levels of pathogenic cytokines (IL-6, IFN-γ and IL-21). After ART treatment, T-cell compartment in the spleen of MRL/lpr mice was restored in terms of reduction in the number of Tfh cells and in the maintenance of the ratio of Tfr to follicular regulatory T cells (Tfh). In addition, ART has significantly inhibited the phosphorylation levels of Jak2 and Stat3 in the MRL/lpr mice.CONCLUSION: ART showed therapeutic effects on lupus-prone MRL/lpr mice by inhibiting the differentiation of Tfh cells as well as altering the activation status of Jak2-Stat3 signaling cascade. Copyright © 2019 Elsevier GmbH
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- Gao, Kai, et al.
(författare)
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Application of Rainbow Trout CYP1 Gene Expression Patterns in Gill and Liver for Haihe River Bio-monitoring
- 2015
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Ingår i: Huanjing Kexue. - 0250-3301. ; 36:10, s. 3878-3883
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Tidskriftsartikel (refereegranskat)abstract
- CYP1 subfamily genes in gills and liver of rainbow trout as biomarkers were studied to establish methods for quantitative mRNA expression analysis of these genes and to determine their expression pattern. Fish caged in various waters in the Haihe River (Tianjin) were analyzed. The mRNA expression patterns observed in Machangjian River and estuary site of Haihe River were markedly similar but at different levels, reflecting that those sites shared the similar pollution components but with different local pollution load. CYP1C1 and 1C3 were only induced at Gegu site and estuary site of Haihe River, indicating different types of CYP1 agonists in Machangjian River. Response patterns of multiple CYP1 genes in gills and liver could be applied in the monitoring strategy. The response patterns of CYP1 genes could be used for better understanding the relationship between complex mixtures of pollutants and biological response of organisms in aquatic environments.
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- Hamdi, Yosr, et al.
(författare)
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Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
- 2017
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
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| 8. |
- Murphy, Christine, et al.
(författare)
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Defying hard-to-heal wounds with an early antibiofilm intervention strategy : 'Wound hygiene'
- 2019
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Ingår i: Journal of Wound Care. - : Mark Allen Group. - 0969-0700 .- 2052-2916. ; 28:12, s. 818-822
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Tidskriftsartikel (refereegranskat)abstract
- Biofilm has been implicated as a barrier to wound healing and it is widely accepted that the majority of wounds not following a normal healing trajectory contain biofilm. Therefore, strategies that inform and engage clinicians to reduce biofilm and optimise the wound tissue environment to enable wound progression are of interest to wound care providers. In March 2019, an advisory board was convened where experts considered the barriers and opportunities to drive a broader adoption of a biofilm-based approach to wound care. Poor clarity and articulation of wound terminology were identified as likely barriers to clinical adoption of rigorous and proactive microbial decontamination that is supportive of wound healing advancement. A transition to an intuitive term such as 'wound hygiene' was proposed to communicate a comprehensive wound decontamination plan with an associated message of expected habitual routine. 'Wound hygiene', is a relatable concept that supports meticulous wound practice that addresses barriers to wound healing, such as biofilm, while aligning with antimicrobial stewardship programmes..
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| 9. |
- Ni, Xiangyin, et al.
(författare)
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Formation of forest gaps accelerates C, N and P release from foliar litter during 4 years of decomposition in an alpine forest
- 2018
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Ingår i: Biogeochemistry. - : Springer Science and Business Media LLC. - 0168-2563 .- 1573-515X. ; 139:3, s. 321-335
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Tidskriftsartikel (refereegranskat)abstract
- Relative to areas under canopy, the soils in forest gaps receive more irradiance and rainfall (snowfall); this change in microclimate induced by forest gaps may influence the release of carbon (C) and nutrients during litter decomposition. However, great uncertainty remains about the effects of forest gaps on litter decomposition. In this study, we incubated foliar litters from six tree and shrub species in forest gaps and canopy plots and measured the release of C, nitrogen (N) and phosphorus (P) in different snow cover periods in an alpine forest from 2012 to 2016. We found that N was retained by 24–46% but that P was immediately released during an early stage of decomposition. However, forest gaps decreased litter N retention, resulting in more N and P being released from decomposing litters for certain species (i.e., larch, birch and willow litters). Moreover, the release of C and nutrients during litter decomposition stimulated by forest gaps was primarily driven by warmer soil temperature in this high-altitude forest. We conclude that gap formation during forest regeneration may accelerate C turnover and nutrient cycling and that this stimulation might be regulated by the litter species in this seasonally snow-covered forest. © 2018, Springer Nature Switzerland AG.
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| 10. |
- Palacio, Montse, et al.
(författare)
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Prediction of neonatal respiratory morbidity by quantitative ultrasound lung texture analysis: a multicenter study.
- 2017
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Ingår i: American journal of obstetrics and gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 217:2
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Tidskriftsartikel (refereegranskat)abstract
- Prediction of neonatal respiratory morbidity may be useful to plan delivery in complicated pregnancies. The limited predictive performance of the current diagnostic tests together with the risks of an invasive procedure limits the use of fetal lung maturity assessment.The objective of the study was to evaluate the performance of quantitative ultrasound texture analysis (quantusFLM) to predict neonatal respiratory morbidity in preterm and early-term (<39.0 weeks) deliveries.This was a prospective multicenter study in 20 centers worldwide. Fetal lung ultrasound images were obtained at 25.0-38.6 weeks' gestation within 48 hours of delivery, stored in Digital Imaging and Communication in Medicine format, and analyzed with quantusFLM. Physicians were blinded to the analysis. At delivery, perinatal outcomes and the occurrence of neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, were registered. The performance of the ultrasound texture analysis test to predict neonatal respiratory morbidity was evaluated.A total of 883 images were collected, but 17.2% were discarded because of poor image quality or exclusion criteria, leaving 730 observations for the final analysis. The prevalence of neonatal respiratory morbidity was 13.8% (101 of 730). The quantusFLM predicted neonatal respiratory morbidity with a sensitivity, specificity, and positive and negative predictive value of 74.3% (75 of 101), 88.6% (557 of 629), 51.0% (75 of 147), and 95.5% (557 of 583), respectively. Accuracy was 86.5% (632 of 730) and positive and negative likelihood ratios were 6.5 and 0.3, respectively.The quantusFLM predicted neonatal respiratory morbidity with an accuracy similar to that previously reported for other tests with the advantage of being a noninvasive technique.
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