SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(He Chunyan) "

Sökning: WFRF:(He Chunyan)

  • Resultat 1-10 av 10
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Elks, Cathy E, et al. (författare)
  • Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
  • 2010
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
  •  
2.
  • Stolk, Lisette, et al. (författare)
  • Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
  • 2012
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 44:3, s. 260-268
  • Tidskriftsartikel (refereegranskat)abstract
    • To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
  •  
3.
  • Barban, Nicola, et al. (författare)
  • Genome-wide analysis identifies 12 loci influencing human reproductive behavior
  • 2016
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 48:12, s. 1462-1472
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetic architecture of human reproductive behavior age at first birth (AFB) and number of children ever born (NEB) has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.
  •  
4.
  • Perry, John R. B., et al. (författare)
  • Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche
  • 2014
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 514:7520, s. 92-
  • Tidskriftsartikel (refereegranskat)abstract
    • Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-causemortality(1). Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation(2,3), but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.
  •  
5.
  • Song, Dandan, et al. (författare)
  • Blocking Fra-1 sensitizes triple-negative breast cancer to PARP inhibitor
  • 2021
  • Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 506, s. 23-34
  • Tidskriftsartikel (refereegranskat)abstract
    • The AP-1 member Fra-1 is overexpressed in TNBC and plays crucial roles in tumor progression and treatment resistance. In a previous large-scale screen, we identified PARP1 to be among 118 proteins that interact with endogenous chromatin-bound Fra-1 in TNBC cells. PARP1 inhibitor (olaparib) is currently in clinical use for treatment of BRCA-mutated TNBC breast cancer. Here, we demonstrate that the Fra-1-PARP1 interaction impacts the efficacy of olaparib treatment. We show that PARP1 interacts with and downregulates Fra-1, thereby reducing AP-1 transcriptional activity. Olaparib treatment, or silencing of PARP1, consequently, increases Fra-1 levels and enhances its transcriptional activity. Increased Fra-1 can have adverse effect, including treatment resistance. We also found that a large fraction of PARP1-regulated genes was dependent on Fra-1. We show that by inhibiting Fra-1/AP-1, non-BRCA-mutated TNBC cells can become sensitized to olaparib treatment. We identify that high PARP1 expression is indicative of a poor clinical outcome in breast cancer patients overall (P = 0.01), but not for HER-2 positive patients. In conclusion, by exploring the functionality of the Fra-1 and PARP1 interaction, we propose that targeting Fra-1 could serve as a combinatory therapeutic approach to improve olaparib treatment outcome for TNBC patients.
  •  
6.
  • Chen, Zhiwen, et al. (författare)
  • Interface engineering of NiS@MoS2 core-shell microspheres as an efficient catalyst for hydrogen evolution reaction in both acidic and alkaline medium
  • 2021
  • Ingår i: Journal of Alloys and Compounds. - : ELSEVIER SCIENCE SA. - 0925-8388 .- 1873-4669. ; 853
  • Tidskriftsartikel (refereegranskat)abstract
    • Electrochemical splitting of water is one of the most reliable and effective ways for the sustainable production of pure hydrogen on a large scale, while the core of this technology lies in the development of highly active non-noble-metal-based electrocatalysts to lower the large dynamic overpotentials of electrode materials. Here, an interface engineering strategy is demonstrated to construct an efficient and stable catalyst based on NiS@MoS2 core-shell hierarchical microspheres for the hydrogen evolution reactions (HER). The ultrathin MoS2 nanosheets in-situ grow on the surface of NiS hierarchical micro-sized spheres constructed by porous nanoplates, endowing the composites with rich interfaces, well-exposed electroactive edges, high structural porosity and fast transport channels. These advantages are favorable for the improvement of catalytic sites and the transport of catalysis-relevant species. More importantly, the intimate contact between MoS2 nanosheets and NiS nanoplates synergistically favors the chemical sorption of hydrogen intermediates, thereby reducing the reaction barrier and accelerating the HER catalytic process. As a result, the optimized NiS@MoS2 catalyst manifests impressive HER activity and durability, with a low overpotential of 208 mV in 0.5 M H2SO4 and 146 mV in 1.0 M KOH at 10 mA cm(-2), respectively. This work not only provides an effective way to construct core-shell hierarchical microspheres but also a multiscale strategy to regulate the electronic structure of heterostructured materials for energy-related applications. (C) 2020 Elsevier B.V. All rights reserved.
  •  
7.
  • Coviello, Andrea D, et al. (författare)
  • A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.
  • 2012
  • Ingår i: PLoS genetics. - : Public Library of Science. - 1553-7404 .- 1553-7390. ; 8:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8×10(-106)), PRMT6 (rs17496332, 1p13.3, p = 1.4×10(-11)), GCKR (rs780093, 2p23.3, p = 2.2×10(-16)), ZBTB10 (rs440837, 8q21.13, p = 3.4×10(-09)), JMJD1C (rs7910927, 10q21.3, p = 6.1×10(-35)), SLCO1B1 (rs4149056, 12p12.1, p = 1.9×10(-08)), NR2F2 (rs8023580, 15q26.2, p = 8.3×10(-12)), ZNF652 (rs2411984, 17q21.32, p = 3.5×10(-14)), TDGF3 (rs1573036, Xq22.3, p = 4.1×10(-14)), LHCGR (rs10454142, 2p16.3, p = 1.3×10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p = 2.7×10(-08)), and UGT2B15 (rs293428, 4q13.2, p = 5.5×10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5×10(-08), women p = 0.66, heterogeneity p = 0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ∼15.6% and ∼8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
  •  
8.
  • Huang, Shoushuang, et al. (författare)
  • An advanced electrocatalyst for efficient synthesis of ammonia based on chemically coupled NiS@MoS2 heterostructured nanospheres
  • 2021
  • Ingår i: Sustainable Energy & Fuels. - : ROYAL SOC CHEMISTRY. - 2398-4902.
  • Tidskriftsartikel (refereegranskat)abstract
    • The electrochemical reduction of nitrogen, as a sustainable alternative to the known Haber-Bosch process, possesses promising application prospects in the development of renewable energy storage systems. However, the yield of NH3 and Faraday efficiency are usually very low owing to the loss of active electrocatalysts and competitive hydrogen evolution reactions. Herein, uniform NiS@MoS2 core-shell microspheres are controllably prepared as a potential catalyst for an ambient electrocatalytic N-2 reduction reaction. The NiS@MoS2 microspheres possess highly active intrinsic, sufficient accessible active sites, high structural porosity, and convenient transport channels, consequently boosting the transmission of electrons and mass. Additionally, the interfacial interaction between NiS and MoS2 facilitates electron transfer, which further improves the catalytic activity by optimizing the free energies of reaction intermediates. As a result, the titled NiS@MoS2 shows excellent electrochemical activity and selectivity, capable of achieving a relatively high NH3 yield of 9.66 mu g h(-1) mg(cat)(-1) at -0.3 V (vs. the reversible hydrogen electrode, RHE) and a high FE of 14.8% at -0.1 V vs. RHE in 0.1 M Na2SO4. The work demonstrated here may open a new avenue for the rational design and synthesis of catalysts for the electrochemical synthesis of ammonia.
  •  
9.
  • Lunetta, Kathryn L., et al. (författare)
  • Rare coding variants and X-linked loci associated with age at menarche
  • 2015
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723 .- 2041-1723. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only similar to 3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency proteincoding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P<5 x 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P = 9.4 x 10(-13)) and FAAH2 (rs5914101, P = 4.9 x 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P = 2.8 x 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain similar to 0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.
  •  
10.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 10
 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy