| 1. |
- Li, Chunyan, et al.
(författare)
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Pathways related to mitochondrial dysfunction in cartilage of endemic osteoarthritis patients in China
- 2012
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Ingår i: Science China Life Sciences. - : Springer Science+Business Media B.V.. - 1674-7305 .- 1869-1889. ; 55:12, s. 1057-1063
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Tidskriftsartikel (refereegranskat)abstract
- n this paper, we present the first evidence of differences in the mitochondria-related gene expression profiles of adult articular cartilage derived from patients with Kashin-Beck disease and normal controls. The expression of 705 mitochondria-related genes was analyzed by mitochondria-related gene expression analysis and ingenuity pathways analysis. Mitochondria-related gene expression analysis identified 9 up-regulated genes in Kashin-Beck disease based on their average expression ratio. Three canonical pathways involved in oxidative phosphorylation, apoptosis signaling and pyruvate metabolism were identified, which indicate the involvement of mitochondrial dysfunction in the pathogenesis of Kashin-Beck disease.
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| 2. |
- Ren, Chunyan, et al.
(författare)
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Structure-Guided Discovery of Selective Antagonists for the Chromodomain of Polycomb Repressive Protein CBX7
- 2016
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Ingår i: ACS Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875 .- 1948-5875. ; 7:6, s. 601-605
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Tidskriftsartikel (refereegranskat)abstract
- The chromobox 7 (CBX7) protein of the polycomb repressive complex 1 (PRC1) functions to repress transcription of tumor suppressor p16 (INK4a) through long noncoding RNA, ANRIL (antisense noncoding RNA in the INK4 locus) directed chromodomain (ChD) binding to trimethylated lysine 27 of histone H3 (H3K27me3), resulting in chromatin compaction at the INK4a/ARF locus. In this study, we report structure-guided discovery of two distinct classes of small-molecule antagonists for the CBX7ChD. Our Class A compounds, a series including analogues of the previously reported MS452, inhibit CBX7ChD/methyl-lysine binding by occupying the H3K27me3 peptide binding site, whereas our Class B compound, the newly discovered MS351, appears to inhibit H3K27me3 binding when CBX7ChD is bound to RNA. Our crystal structure of the CBX7ChD/MS351 complex reveals the molecular details of ligand recognition by the aromatic cage residues that typically engage in methyl-lysine binding. We further demonstrate that MS351 effectively induces transcriptional derepression of CBX7 target genes, including p16 (INK4a) in mouse embryonic stem cells and human prostate cancer PC3 cells. Thus, MS351 represents a new class of ChD antagonists that selectively targets the biologically active form of CBX7 of the PRC1 in long noncoding RNA- and H3K27me3-directed gene transcriptional repression.
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| 3. |
- Song, Lin, et al.
(författare)
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Thalamic gray matter volume mediates the association between KIBRA polymorphism and olfactory function among older adults : a population-based study
- 2022
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 33:7, s. 3664-3673
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Tidskriftsartikel (refereegranskat)abstract
- The kidney and brain expressed protein (KIBRA) rs17070145 polymorphism is associated with both structure and activation of the olfactory cortex. However, no studies have thus far examined whether KIBRA can be linked with olfactory function and whether brain structure plays any role in the association. We addressed these questions in a population-based cross-sectional study among rural-dwelling older adults. This study included 1087 participants derived from the Multidomain Interventions to Delay Dementia and Disability in Rural China, who underwent the brain MRI scans in August 2018 to October 2020; of these, 1016 took the 16-item Sniffin’ Sticks identification test and 634 (62.40%) were defined with olfactory impairment (OI). Data were analyzed using the voxel-based morphometry analysis and general linear, logistic, and structural equation models. The KIBRA rs17070145 C-allele (CC or CT vs. TT genotype) was significantly associated with greater gray matter volume (GMV) mainly in the bilateral orbitofrontal cortex and left thalamus (P < 0.05) and with the multi-adjusted odds ratio of 0.73 (95% confidence interval 0.56–0.95) for OI. The left thalamic GMV could mediate 8.08% of the KIBRA-olfaction association (P < 0.05). These data suggest that the KIBRA rs17070145 C-allele is associated with a reduced likelihood of OI among older adults, partly mediated through left thalamic GMV.
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| 4. |
- Deng, Min, et al.
(författare)
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Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
- 2013
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 45:6, s. 697-
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
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| 5. |
- Elks, Cathy E, et al.
(författare)
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Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
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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.
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| 6. |
- Lunetta, Kathryn L., et al.
(författare)
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Rare coding variants and X-linked loci associated with age at menarche
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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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.
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| 7. |
- Ma, Chunyan, et al.
(författare)
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Molar enthalpy of mixing and refractive indices of choline chloride-based deep eutectic solvents with water
- 2017
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Ingår i: Journal of Chemical Thermodynamics. - : Elsevier. - 0021-9614 .- 1096-3626. ; 105, s. 30-36
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Tidskriftsartikel (refereegranskat)abstract
- The molar enthalpies of mixing were measured for binary systems of choline chloride-based deep eutectic solvents (glycerol, ethylene glycol and malonic acid) with water at 298.15 K and 308.15 K, and atmospheric pressure with an isothermal calorimeter. Refractive indices were also measured at 303.15 K and atmospheric pressure. The binary mixtures of {chcl/glycerol (1:2) + water, chcl/ethylene glycol (1:2) + water} showed exothermic behaviour over the entire range of composition, while the binary mixture of {chcl/malonic acid (1:1) + water} showed endothermic behaviour at first and then changed to be exothermic with the increasing content of chcl/malonic acid (1:1). Experimental refractive indices were fitted with the Redlich–Kister equation, and experimental molar enthalpies of mixing were correlated with the Redlich–Kister equation and the non-random two-liquid (NRTL) model. The NRTL model with the fitted parameters was used to predict the vapour pressures of these three mixtures. For mixtures of {chcl/glycerol (1:2) + water} and {chcl/ethylene glycol (1:2) + water}, the predicted vapour pressures agreed well with the experimental reults from the literature. While for mixture of {chcl/malonic acid (1:1)+water}, the predicted vapour pressures showed deviation at the high concentration of chcl/malonic acid (1:1), and this was probably because of the complex molecular interaction between chcl/malonic acid (1:1) and water
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| 8. |
- Ma, Chunyan, et al.
(författare)
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Molar Enthalpy of Mixing for Choline Chloride/Urea Deep EutecticSolvent + Water System
- 2016
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Ingår i: Journal of Chemical and Engineering Data. - : American Chemical Society (ACS). - 0021-9568 .- 1520-5134. ; 61:12, s. 4172-4177
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Tidskriftsartikel (refereegranskat)abstract
- The molar enthalpies of mixing for binary systems of choline chloride (chcl)/urea deep eutectic solvents (mole ratios of 1:1.5, 1:2, and 1:2.5) with water were measured at 308.15 and 318.15 K under atmospheric pressure with an isothermal calorimeter. The binary mixture of (chcl/urea (1:2.5) + water) showed endothermic behavior over the entire range of compositions, while the binary mixtures of (chcl/urea (1:1.5) + water) and (chcl/urea (1:2) + water) showed endothermic behavior first and then was changed to be exothermic with increasing content of deep eutectic solvents. The Redlich–Kister (RK) equation and the nonrandom two-liquid (NRTL) model were used to fit experimental molar enthalpies of mixing. The NRTL model with the fitted parameters was further used to predict the vapor pressure for the three systems and was compared with the experimental data from literature. For the binary mixtures of (chcl/urea (1:2) + water), the predicted vapor pressure agreed well with the experimental data only when the temperature was lower than 333.15 K and the mole fraction of chcl/urea (1:2) was lower than 0.1. Otherwise, the deviation increased greatly with an increase of the amount of chcl/urea (1:2).
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| 9. |
- Piculell, Maria, et al.
(författare)
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The inhibitory effects of reject water on nitrifying populations grown at different biofilm thickness
- 2016
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Ingår i: Water Research. - : Elsevier BV. - 0043-1354 .- 1879-2448. ; 104:1 Nov, s. 292-302
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Tidskriftsartikel (refereegranskat)abstract
- Suppression of nitrite oxidizing bacteria (NOB) is of vital importance to achieve successful, energy efficient, mainstream anammox processes for wastewater treatment. In this study, biofilm carriers from a fully nitrifying MBBR system, fed with mainstream wastewater, were temporarily exposed to reject water from sludge dewatering, to evaluate this as a possible strategy to inhibit NOB and achieve nitrite production under realistic conditions. Two different carrier types were compared, in which biofilm thickness was maintained at approximately 400 and 50 mm, respectively, and reject treatment was tested at different exposure time and loading rates. Reject exposure almost always resulted in an increased nitrite production in the thinner biofilm, and overall, nitrifiers growing in the thin biofilm were more sensitive than those grown in the thicker biofilm. The effect from reject exposure remained in the systems for four days after returning to mainstream operation, with nitrite production gradually increasing for three days. Increased concentrations of free ammonia correlated with reject exposure and may be the cause of inhibition, although other factors cannot be excluded.
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| 10. |
- Qu, Yanhua, 1974-, et al.
(författare)
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The evolution of ancestral and species-specific adaptations in snowfinches at the Qinghai-Tibet Plateau
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 10.1073/pnas.2012398118:13, s. e2012398118-e2012398118
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Tidskriftsartikel (refereegranskat)abstract
- Species in a shared environment tend to evolve similar adaptations under the influence of their phylogenetic context. Using snowfinches, a monophyletic group of passerine birds (Passeridae), we study the relative roles of ancestral and species-specific adaptations to an extreme high-elevation environment, the Qinghai–Tibet Plateau. Our ancestral trait reconstruction shows that the ancestral snowfinch occupied high elevations and had a larger body mass than most nonsnowfinches in Passeridae. Subsequently, this phenotypic adaptation diversified in the descendant species. By comparing high-quality genomes from representatives of the three phylogenetic lineages, we find that about 95% of genes under positive selection in the descendant species are different from those in the ancestor. Consistently, the biological functions enriched for these species differ from those of their ancestor to various degrees (semantic similarity values ranging from 0.27 to 0.5), suggesting that the three descendant species have evolved divergently from the initial adaptation in their common ancestor. Using a functional assay to a highly selective gene, DTL, we demonstrate that the nonsynonymous substitutions in the ancestor and descendant species have improved the repair capacity of ultraviolet-induced DNA damage. The repair kinetics of the DTL gene shows a twofold to fourfold variation across the ancestor and the descendants. Collectively, this study reveals an exceptional case of adaptive evolution to high-elevation environments, an evolutionary process with an initial adaptation in the common ancestor followed by adaptive diversification of the descendant species.
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