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Sökning: WFRF:(Liang Xiaolin)

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1.
  • Hong, Liang, et al. (författare)
  • Structure and Dynamics of a Compact State of a Multidomain Protein, the Mercuric Ion Reductase
  • 2014
  • Ingår i: Biophysical Journal. - : Cell Press. - 1542-0086. ; 107:2, s. 393-400
  • Tidskriftsartikel (refereegranskat)abstract
    • The functional efficacy of colocalized, linked protein domains is dependent on linker flexibility and system compaction. However, the detailed characterization of these properties in aqueous solution presents an enduring challenge. Here, we employ a novel, to our knowledge, combination of complementary techniques, including small-angle neutron scattering, neutron spin-echo spectroscopy, and all-atom molecular dynamics and coarse-grained simulation, to identify and characterize in detail the structure and dynamics of a compact form of mercuric ion reductase (MerA), an enzyme central to bacterial mercury resistance. MerA possesses metallochaperone-like N-terminal domains (NmerA) tethered to its catalytic core domain by linkers. The NmerA domains are found to interact principally through electrostatic interactions with the core, leashed by the linkers so as to subdiffuse on the surface over an area close to the core C-terminal Hg(II)-binding cysteines. How this compact, dynamical arrangement may facilitate delivery of Hg(II) from NmerA to the core domain is discussed.
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2.
  • Begg, Colin B, et al. (författare)
  • Variation of breast cancer risk among BRCA1/2 carriers
  • 2008
  • Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association. - 1538-3598. ; 299:2, s. 194-201
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: The risk of breast cancer in BRCA1 and BRCA2 mutation carriers has been examined in many studies, but relatively little attention has been paid to the degree to which the risk may vary among carriers. OBJECTIVES: To determine the extent to which risks for BRCA1 and BRCA2 carriers vary with respect to observable and unobservable characteristics. DESIGN, SETTING, AND PARTICIPANTS: Probands were identified from a population-based, case-control study (Women's Environmental Cancer and Radiation Epidemiology [WECARE]) of asynchronous contralateral breast cancer conducted during the period of January 2000 to July 2004. Participants previously diagnosed with contralateral breast cancer or unilateral breast cancer were genotyped for mutations in BRCA1 and BRCA2. All participants had their initial breast cancer diagnosed during the period of January 1985 to December 2000, before the age of 55 years. MAIN OUTCOME MEASURE: Incidence of breast cancer in first-degree female relatives of the probands was examined and compared on the basis of proband characteristics and on the basis of variation between families. RESULTS: Among the 1394 participants with unilateral breast cancer, 73 (5.2%) were identified as carriers of deleterious mutations (42 with BRCA1 and 31 with BRCA2). Among the 704 participants with contralateral breast cancer, 108 (15.3%) were identified as carriers of deleterious mutations (67 with BRCA1 and 41 with BRCA2). Among relatives of carriers, risk was significantly associated with younger age at diagnosis in the proband (P = .04), and there was a trend toward higher risk for relatives of contralateral breast cancer vs unilateral breast cancer participants (odds ratio, 1.4 [95% confidence interval, 0.8-2.4]; P = .28). In addition, there were significant differences in risk between carrier families after adjusting for these observed characteristics. CONCLUSION: There exists broad variation in breast cancer risk among carriers of BRCA1 and BRCA2 mutations.
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3.
  • Bernstein, Jonine L., et al. (författare)
  • Contralateral breast cancer after radiotherapy among BRCA1 and BRCA2 mutation carriers: A WECARE Study Report
  • 2013
  • Ingår i: European Journal of Cancer. - : Elsevier. - 1879-0852. ; 49:14, s. 2979-2985
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Women with germline BRCA1 or BRCA2 (BRCA1/BRCA2) mutations are at very high risk of developing breast cancer, including asynchronous contralateral breast cancer (CBC). BRCA1/BRCA2 genes help maintain genome stability and assist in DNA repair. We examined whether the risk of CBC associated with radiation treatment was higher among women with germline BRCA1/BRCA2 mutations than among non-carriers. Methods: A population-based, nested case-control study was conducted within a cohort of 52,536 survivors of unilateral breast cancer (UBC). Cases were 603 women with CBC and controls were 1199 women with UBC individually matched on age at diagnosis, race, year of first diagnosis and cancer registry. All women were tested for BRCA1 and BRCA2 mutations. Radiation absorbed dose from the initial radiotherapy (RT) to the CBC location within the contralateral breast was reconstructed from measurements in a tissue-equivalent phantom and details available in the therapy records. Findings: Among women treated with radiation, the mean radiation dose was 1.1 Gy (range = 0.02-6.2 Gy). Risk of developing CBC was elevated among women who carried a deleterious BRCA1/BRCA2 mutation (rate ratio, RR = 4.5, confidence interval, CI = 3.0-6.8), and also among those treated with RT (RR = 1.2, CI = 1.0-1.6). However, among mutation carriers, an incremental increase in risk associated with radiation dose was not statistically significant. Interpretation: Multiplicative interaction of RT with mutation status would be reflected by a larger association of RT with CBC among carriers than among non-carriers, but this was not apparent. Accordingly, there was no clear indication that carriers of deleterious BRCA/BRCA2 mutations were more susceptible to the carcinogenic effects of radiation than non-carriers. These findings are reassuring and have important clinical implications for treatment decisions and the clinical management of patients harbouring deleterious BRCA1/BRCA2 mutations. Funding: All work associated with this study was supported by the U.S. National Cancer Institute [R01CA097397, U01CA083178]. (C) 2013 Elsevier Ltd. All rights reserved.
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4.
  • Borg, Åke, et al. (författare)
  • Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.
  • 2010
  • Ingår i: Human Mutation. - : John Wiley & Sons Inc.. - 1059-7794. ; 31, s. 1200-1240
  • Tidskriftsartikel (refereegranskat)abstract
    • BRCA1 and BRCA2 screening in women at high-risk of breast cancer results in the identification of both unambiguously defined deleterious mutations and sequence variants of unknown clinical significance (VUS). We examined a population-based sample of young women with contralateral breast cancer (CBC, n=705) or unilateral breast cancer (UBC, n=1398). We identified 470 unique sequence variants, of which 113 were deleterious mutations. The remaining 357 VUS comprised 185 unique missense changes, 60% were observed only once, while 3% occurred with a frequency of >10%. Deleterious mutations occurred three times more often in women with CBC (15.3%) than in women with UBC (5.2%), whereas combined, VUS were observed in similar frequencies in women with CBC and UBC. A protein alignment algorithm defined 16 rare VUS, occurring at highly conserved residues and/or conferring a considerable biochemical difference, the majority located in the BRCA2 DNA-binding domain. We confirm a multiplicity of BRCA1 and BRCA2 VUS that occur at a wide range of allele frequencies. Although some VUS inflict chemical differences at conserved residues, suggesting a deleterious effect, the majority are not associated with an increased risk of CBC. (c) 2010 Wiley-Liss, Inc.
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5.
  • Duan, Xiaolin, et al. (författare)
  • Early Cambrian (Stage 4) brachiopods from the Shipai Formation in the Three Gorges area of South China
  • 2021
  • Ingår i: Journal of Paleontology. - : Cambridge University Press (CUP). - 0022-3360 .- 1937-2337. ; 95:3, s. 497-526
  • Tidskriftsartikel (refereegranskat)abstract
    • Diverse and abundant fossil taxa have been described in the lower Cambrian Shipai Formation in the Three Gorges area of Hubei Province, South China, but the taxonomy and diversity of the co-occurring brachiopod fauna are still far from clear. Here we describe the brachiopod fauna recovered from the Shipai Formation in the Three Gorges area of South China, including representatives of the subphylum Linguliformea: linguloids (Lingulellotreta ergalievi, Eoobolus malongensis, and Neobolidae gen. indet. sp. indet.), and an acrotretoid (Linnarssonia sapushanensis); and representatives from the subphylum Rhynchonelliformea: the calcareous-shelled Kutorginates (Kutorgina sinensis, Kutorgina sp., and Nisusia liantuoensis). This brachiopod assemblage and the first occurrence of Linnarssonia sapushanensis shell beds permit correlation of the Shipai Formation in the Three Gorges area of Hubei Province with the Stage 4 Wulongqing Formation in the Wuding area of eastern Yunnan. This correlation is further strengthened by the first appearance datum (FAD) of the rhynchonelliform brachiopod Nisusia in the upper silty mudstone of both the Shipai and Wulongqing formations. The new well-preserved material, derived from siliciclastic rocks, also gives critical new insights into the fine shell structure of L. sapushanensis. Microstructural studies on micromorphic acrotretoids (like Linnarssonia) have previously been restricted to fossils that were acid-etched from limestones. This is the first study to carry out detailed comparative ultrastructural studies on acrotretoid shells preserved in siliciclastic rocks. This work reveals a hollow tube and solid column microstructure in the acrotretoid shells from the Shipai Formation, which is likely to be equivalent of traditional column and central canal observed in shells dissolved from limestones.
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6.
  • Duan, Xiaolin, et al. (författare)
  • First report of acrotretoid brachiopod shell beds in the lower Cambrian (Stage 4) Guanshan Biota of eastern Yunnan, South China
  • 2021
  • Ingår i: Journal of Paleontology. - 0022-3360 .- 1937-2337. ; 95:1, s. 40-55
  • Tidskriftsartikel (refereegranskat)abstract
    • Brachiopod shell accumulations are abundant and diverse in the lower Cambrian strata of Yunnan Province, South China, but most commonly they are composed of linguloid and acrotheloid brachiopods. Here, we describe the first record of shell beds with high-density accumulations of microscopic acrotretoid brachiopods (usually <2 mm in width) in the muddy deposits of the Wulongqing Formation (Guanshan Biota, Cambrian Stage 4) in the Wuding area of Yunnan Province. The acrotretoid shell beds from the Wulongqing Formation vary from thin mm-thick pavements to more well-developed beds, several centimeters thick. The occurrence of remarkably rich acrotretoid shell beds indicates that microscopic lingulates began to exert an important role in hardening and paving the soft-substrate seafloor during the early Cambrian evolution of Phanerozoic “mixgrounds.” The new Guanshan material is referred to a new species, Linnarssonia sapushanensis n. sp., which differs from other species of Linnarssonia mainly in having a well-developed internal pedicle tube, as well as a relatively longer dorsal median septum. The occurrence of Linnarssonia sapushanensis n. sp. in the Wulongqing Formation in eastern Yunnan extend the oldest record of the genus on the Yangtze Platform of South China back to at least Cambrian Stage 4.
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7.
  • Hu, Yazhou, et al. (författare)
  • First Report of Small Shelly Fossils from the Cambrian Miaolingian Limestones (Zhangxia and Hsuzhuang Formations) in Yiyang County, Henan Province of North China
  • 2021
  • Ingår i: Minerals. - : MDPI AG. - 2075-163X .- 2075-163X. ; 11:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Small Shelly Fossils (SSFs) from the Cambrian are widely distributed and well known across different paleocontinents of the world. However, middle Cambrian SSFs from North China Platform have only rarely been documented until now. In this paper, we presented the first report on SSFs from bioclastic and oolitic limestones of the Zhangxia and Hsuzhuang formations of Henan province, North China. The carbonate-hosted fauna includes brachiopods (Micromitra sp., M. modesta, Eoobolus sp., and Schizopholis sp.), helcionellids (Oelandiellaaccordionata and O. aliciae), hyolithids, Hyolithellus sp., Chancelloriaeros, sponge spicules, echinoderm ossicles, and chancelloriid sclerites. In terms of preservation, the brachiopod shell valves of M. modesta appeared to be homogeneous, consisting of tightly packed phosphate grains. Eoobolus sp. is composed of primary layer and secondary baculate, both of which consist of tightly compacted phosphate grains. Schizopholis sp. has multiple-lamellar phosphatized microstructures that distinctly differ from the other brachiopods recovered from the Longwanggou section. A similar multiple-lamellar microstructure was also revealed in conchs of Hyolithellus, with tightly compacted phosphate grains. The argillaceous shell of Oelandiellaaccordionata and O. aliciae, and the calcitic inner molds of hyolith did not preserve any shell structure. The helcionellids O. accordionata and O. aliciae and the brachiopod M. modesta were reported for the first time from North China. The fauna is most similar to the middle Cambrian faunas of South Australia, in the brachiopod and mollusk components; it is also similar in composition of brachiopods and mollusks to coeval faunas from South China. The new fauna of SSFs in the Yiyang Longwanggou Section indicated that the Hsuzhuang and Zhangxia formations are late Drumian to middle Guzhuangian in age, most likely correlating with the Murrawong Creek Formation of South Australia.
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8.
  • Liang, Yue, et al. (författare)
  • Brachiopods from the Latham Shale Lagerstätte (Cambrian Series 2, Stage 4) and Cadiz Formation (Miaolingian, Wuliuan), California
  • 2022
  • Ingår i: Journal of Paleontology. - : Cambridge University Press. - 0022-3360 .- 1937-2337. ; 96:1, s. 61-80
  • Tidskriftsartikel (refereegranskat)abstract
    • A moderately diverse assemblage of brachiopods from the Latham Shale Lagerstätte (Cambrian Series 2, upper Stage 4) and the upper Cadiz Formation (Miaolingian, Wuliuan), California is described in detail for the first time. The fauna includes both linguliform and rhynchonelliform brachiopods—Hadrotreta primaea (Walcott, 1902), Paterina prospectensis (Walcott, 1884), Dictyonina pannula (White, 1874), and Mickwitzia occidens Walcott, 1908; and Nisusia fulleri Mount, 1981 and Wimanella highlandensis (Walcott, 1886), respectively—together with olenellid trilobites and hyolithids. The fauna differs from other Cambrian Konservat-Lagerstätten (notably Cambrian Series 2 Chengjiang and Guanshan Lagerstätten, eastern Yunnan) in that the brachiopod shell valves in many cases are still preserved with their original mineralization. Moreover, the excellently preserved shale-hosted valves even include cases with exquisite epithelial cell molds, otherwise only seen in acid-etched material from carbonate rocks. The pitted ornamentation in D. pannula closely resembles that described from Ordovician linguliforms. The unusual preservation of N. fulleri provides important clues for ancestral composition of the brachiopod shell. The two articulated rhynchonelliform species probably represent the oldest records of this group from the west Laurentia. The fauna could also represent the earliest onset of the transition from the Cambrian Evolutionary Fauna (CEF) to the Paleozoic Evolutionary Fauna (PEF).
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9.
  • Machiela, Mitchell J., et al. (författare)
  • Characterization of Large Structural Genetic Mosaicism in Human Autosomes
  • 2015
  • Ingår i: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
  • Tidskriftsartikel (refereegranskat)abstract
    • Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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10.
  • Machiela, Mitchell J, et al. (författare)
  • Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
  • 2016
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723 .- 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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