共查询到16条相似文献,搜索用时 0 毫秒
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Davide Gentilini Paolo Garagnani Serena Pisoni Maria Giulia Bacalini Luciano Calzari Daniela Mari Giovanni Vitale Claudio Franceschi Anna Maria Di Blasio 《Aging》2015,7(8):568-576
In this study we applied a new analytical strategy to investigate the relations between stochastic epigenetic mutations (SEMs) and aging. We analysed methylation levels through the Infinium HumanMethylation27 and HumanMethylation450 BeadChips in a population of 178 subjects ranging from 3 to 106 years. For each CpG probe, epimutated subjects were identified as the extreme outliers with methylation level exceeding three times interquartile ranges the first quartile (Q1-(3 × IQR)) or the third quartile (Q3+(3 × IQR)). We demonstrated that the number of SEMs was low in childhood and increased exponentially during aging. Using the HUMARA method, skewing of X chromosome inactivation (XCI) was evaluated in heterozygotes women. Multivariate analysis indicated a significant correlation between log(SEMs) and degree of XCI skewing after adjustment for age (β = 0.41; confidence interval: 0.14, 0.68; p-value = 0.0053). The PATH analysis tested the complete model containing the variables: skewing of XCI, age, log(SEMs) and overall CpG methylation. After adjusting for the number of epimutations we failed to confirm the well reported correlation between skewing of XCI and aging. This evidence might suggest that the known correlation between XCI skewing and aging could not be a direct association but mediated by the number of SEMs. 相似文献
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Ghazi Chabchoub 《World Journal of Rheumatology》2013,3(3):12-15
The pathogenesis of autoimmune diseases (AIDs) is characterized by a female preponderance. The causes for this sex imbalance are based on several hypotheses. One of the most intriguing hypotheses is related to an X chromosome inactivation (XCI) process. Females are mosaics for two cell populations, one with the maternal and one with the paternal X as the active chromosome. Skewed XCI is often defined as a pattern where 80% or more of the cells show a preferential inactivation of one X chromosome. The role of skewed XCI has been questioned in the pathogenesis of several AIDs, such as autoimmune thyroid diseases and rheumatoid arthritis. 相似文献
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Robertson JD Gale RE Wynn RF Dougal M Linch DC Testa NG Chopra R 《British journal of haematology》2000,109(2):272-279
Human haemopoiesis undergoes profound changes throughout life, resulting in compromised regenerative capacity of haemopoietic stem cells. It has been suggested that telomere shortening results in senescence of haemopoietic stem cell subsets and may influence the balance between stem cell renewal and proliferation. Telomere length and telomerase activity was measured in whole blood leucocytes, neutrophils and T cells from cord blood and individuals aged from 1 year to 96 years. Rapid telomere shortening [700 base pairs (bp)] was demonstrated in the first year of life, followed by a gradual decline of 31 bp/year. T cells were shown to have longer telomeres than neutrophils (mean difference 372 bp, P = < 0.001) but demonstrated similar rates of shortening (20 +/- 0.3 bp/year vs. 22 +/- 0.3 bp/year). Telomerase was detectable in T cells but not in neutrophils, suggesting that telomerase is not the rate-limiting step for regulation of telomere length in haemopoietic cells. Stem cell utilization as measured by X chromosome inactivation patterns was found to be independent of telomere length. This supports the concept that age-dependent skewed haemopoiesis is the result of random stem cell loss or X-allelic exclusion rather than telomeric senescence. These studies provide insight into the ageing process and a reference point for evaluating replicative stress in individuals of different age groups. 相似文献
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Random X chromosome inactivation in a female with a variant of Wiskott-Aldrich syndrome 总被引:1,自引:0,他引:1
A 15-month-old female presented with eczema, thrombocytopenia, recurrent infections and failure to thrive. She had low serum IgM and IgG subclasses and an abnormal lymphocyte proliferative response to periodate in vitro. Molecular X chromosome inactivation analysis, using the polymorphic HUMARA DNA probe, showed that the infant has random X chromosome inactivation. We conclude that she has an atypical form of Wiskott-Aldrich syndrome which may be inherited in an autosomal recessive manner. 相似文献
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K. OKUMURA Y. FUJIMORI A. TAKAGI T. MURATE M. OZEKI K. YAMAMOTO A. KATSUMI T. MATSUSHITA T. NAOE T. KOJIMA 《Haemophilia》2008,14(5):1088-1093
Summary. Female carriers of haemophilia B are usually asymptomatic; however, the disease resulting from different pathophysiological mechanisms has rarely been documented in females. In this study, we investigated the mechanisms responsible for haemophilia B in fraternal female twins. We sequenced the factor IX gene (F9) of the propositus, her father, a severe haemophilia B patient and the other family members. X chromosome inactivation was assessed by the methylation‐sensitive HpaII‐PCR assay using X‐linked polymorphisms in human phosphoglycerate kinase 1 gene (PGK1) and glutamate receptor ionotropic AMPA 3 gene (GRIA3). The twins were found to be heterozygotes with a nonsense mutation (p.Arg384X) inherited from their father. The propositus, more severely affected twin, exhibited a significantly higher percentage of inactivation in the maternally derived X chromosome carrying a normal F9. The other twin also showed a skewed maternal X inactivation, resulting in a patient with mild haemophilia B. Thus, the degree of skewing of maternal X inactivation is closely correlated with the coagulation parameters and the clinical phenotypes of the twins. Furthermore, we identified a crossing‐over in the Xq25–26 region of the maternal X chromosome of the more severely affected twin. This crossing‐over was absent in the other twin, consistent with their fraternal state. Differently skewed X inactivation in the fraternal female twins might cause moderately severe and mild haemophilia B phenotypes, respectively. 相似文献
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Kun Tan Lei An Kai Miao Likun Ren Zhuocheng Hou Li Tao Zhenni Zhang Xiaodong Wang Wei Xia Jinghao Liu Zhuqing Wang Guangyin Xi Shuai Gao Linlin Sui De-Sheng Zhu Shumin Wang Zhonghong Wu Ingolf Bach Dong-bao Chen Jianhui Tian 《Proceedings of the National Academy of Sciences of the United States of America》2016,113(12):3197-3202
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Activation and inactivation of human factor X by proteases derived from Ficus carica 总被引:2,自引:0,他引:2
We investigated the effect of proteases derived from Ficus carica (common fig) on human blood coagulation. The milky sap (latex) of several Ficus (F.) species contain ficin, which is a mixture of proteases. Ficin derived from Ficus carica shortened the activated partial thromboplastin time and the prothrombin time of normal plasmas and plasmas deficient in coagulation factors, except plasma deficient in factor X (FX) and generated activated FX (FXa) in defibrinated plasma. Chromatographic separation of ficin from Ficus carica yielded six proteolytic fractions with a different specificity towards FX. We isolated two factor X activators with molecular masses of 23.2 and 23.5 kDa, and studied their action on purified human FX. Factor X was converted to activated FXbeta by consecutive proteolytic cleavage in the heavy chain between Leu178 and Asp179, Arg187 and Gly188, and Arg194and Ile195 (FX numbering system) with concomitant release of a carboxy-terminal peptide. The cleavage pattern of FXa degradation products in the light chain was influenced by Ca2+ and Mn2+. These data suggest the haemostatic potency of Ficus proteases is based on activation of human coagulation factor X. 相似文献
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Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase 总被引:2,自引:0,他引:2 下载免费PDF全文
Hernández-Muñoz I Lund AH van der Stoop P Boutsma E Muijrers I Verhoeven E Nusinow DA Panning B Marahrens Y van Lohuizen M 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(21):7635-7640
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Nouha Bouali Dorra Hmida Soumaya Mougou Jérôme Bouligand Besma Lakhal Sarra Dimessi Bruno Francou Ghada Saad Saoussen Trabelsi Monia Zaouali Moez Gribaa Molka Chaieb Mouhamed Bibi Anne Guiochon-Mantel Ali Saad 《Annales d'endocrinologie》2015,76(6):671-678