Humans have been exposed to many environmental challenges since their evolutionary origins in Africa and subsequent migrations to the rest of the world. A severe environmental challenge to human migrants was hypoxia c...Humans have been exposed to many environmental challenges since their evolutionary origins in Africa and subsequent migrations to the rest of the world. A severe environmental challenge to human migrants was hypoxia caused by low barometric oxygen pressure at high altitudes. Several genome-wide scans have elucidated the genetic basis of human high-altitude adaptations.However, the dearth of functional variant information has led to the successful association of only a few candidate genes. In the present study, we employed a candidate gene approach and re-sequenced the EDAR locus in 45 Tibetan individuals to identify mutations involved in hypoxia adaptation. We identified 10 and five quantitative trait-associated mutations for oxygen saturation (SaO_2) and blood platelet count, respectively, at the EDAR locus. Among these, rs10865026 and rs3749110 (associated with SaO_2 and platelet count, respectively) were identified as functional candidate targets. These data demonstrate that EDAR has undergone natural selection in recent human history and indicate an important role of EDAR variants in Tibetan high-altitude adaptations.展开更多
The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene...The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300 （histone acetyltransferase p300）, we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide （NO） concentration. Collectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.展开更多
People living on the high plateaus of the world have long fascinated biological anthropologists and geneticists because they live in ＂thin air＂ and epitomize an extreme of human biological adaptation.
The impact of surface sensible heating over the Tibetan Plateau （SHTP） on the western Pacific subtropical high （WPSH） with and without air-sea interaction was investigated in this study. Data analysis indicated th...The impact of surface sensible heating over the Tibetan Plateau （SHTP） on the western Pacific subtropical high （WPSH） with and without air-sea interaction was investigated in this study. Data analysis indicated that SHTP acts as a relatively independent factor in modulating the WPSH anomaly compared with ENSO events. Stronger spring SHTP is usually fol- lowed by an enhanced and westward extension of the WPSH in summer, and vice versa. Numerical experiments using both an AGCM and a CGCM confirmed that SHTP influences the large-scale circulation anomaly over the Pacific, which features a barotropic anticyclonic response over the northwestern Pacific and a cyclonic response to the south. Owing to different background circulation in spring and summer, such a response facilitates a subdued WPSH in spring but an en- hanced WPSH in summer. Moreover, the CGCM results showed that the equatorial low-level westerly at the south edge of the cyclonic anomaly brings about a warm SST anomaly （SSTA） in the equatorial central Pacific via surface warm advection. Subsequently, an atmospheric Rossby wave is stimulated to the northwest of the warm SSTA, which in turn enhances the at- mospheric dipole anomalies over the western Pacific. Therefore, the air-sea feedbacks involved tend to reinforce the effect of SHTP on the WPSH anomaly, and the role of SHTP on general circulation needs to be considered in a land-air-sea interaction framework.展开更多
The evident effects of the thermal anomalies over the Tibetan Plateau (TP) and its vicinities are summarized and discussed in this paper. By the singular value decomposition (SVD) technique and numerical simulations o...The evident effects of the thermal anomalies over the Tibetan Plateau (TP) and its vicinities are summarized and discussed in this paper. By the singular value decomposition (SVD) technique and numerical simulations of the effect of the snow depth anomaly over the TP, it is shown that the snow depth anomaly, especially in winter, is one of the factors innuencing precipitation in China, and the winter snow anomaly is more important than the spring one. The relations between the sensible heat anomaly over the TP and the intensity of the South China Sea summer monsoon (SCSSM) are studied, too, and two key areas of the sensible heat anomaly over the TP are found. The relationships between the South Asia High (SAH) and the precipitation in the years with typical droughts or floods in the mid to lower valleys of the Yangtze River (MLVYR) and North China are investigated in some detail. It is found that not only the intensity of the SAH over the TP, but also the 100-hPa height in a large area influences the precipitation in the above two regions. The effects of the SAH on the onsets of the tropical Asian summer monsoon (TASM) including the SCSSM and the tropical Indian summer monsoon (TISM) are studied as well. It is found that the onset times of both the SCSSM and the TISM are highly dependent upon the latitudinal position of the SAH center.展开更多
Allelic variation and genetic diversity at HMW glutenin subunits loci, Glu-A1, Glu-B1and Glu-D1 were investigated in 64 accessions of three unique wheats of western Chinausing sodium dodecyl sulphate polyacrylamide ge...Allelic variation and genetic diversity at HMW glutenin subunits loci, Glu-A1, Glu-B1and Glu-D1 were investigated in 64 accessions of three unique wheats of western Chinausing sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Two HMWglutenin patterns (i.e., null, 7+8, 2+12 and null, 7, 2+12) in 34 Yunnan wheataccessions, 3 HMW glutenin patterns (i.e., null, 7+8, 2+12; null, 6+8, 2+12 andnull, 7+8, 2) in 24 Tibetan accessions and 1 HMW glutenin pattern (null, 7, 2+12) in6 Xinjiang wheat accessions were found. The Tibetan accession TB18 was found to be witha rare subunit 2 encoded by Glu-D1. A total of 4 (i.e., Glu-A1c, Glu-B1a, Glu-B1b andGlu-D1a), 5 (i.e., Glu-A1c, Glu-B1d, Glu-B1b, Glu-D1a and Glu-D1) and 3 alleles (i.e.,Glu-A1c, Glu-B1a and Glu-D1a) at Glu-1 locus were identified among Yunnan, Tibetan andXinjiang unique wheat accessions, respectively. For Yunnan wheat, Tibetan wheat andXinjiang wheat, the Neis mean genetic variation indexes were 0.1574, 0.1366 and 0,respectively, which might indicate the higher genetic diversity at HMW glutenin subunitsloci of Yunnan and Tibetan wheat accessions as compared to that of Xinjiang wheataccessions. Among the three genomes of hexaploid wheats of western China, the highestNeis genetic variation index was appeared in B genome with the mean value of 0.2674,while the indexes for genomes A and D were 0 and 0.0270, respectively. It might bereasonable to indicate that Glu-B1 showed the highest, Glu-D1 the intermediate and Glu-A1 always the lowest genetic diversity.展开更多
In order to constrain the crustal wave velocity structure in the southernTibetan crust and provide insight into the contribution of crustal composition, geothermal gradientand partial melting to the velocity structure...In order to constrain the crustal wave velocity structure in the southernTibetan crust and provide insight into the contribution of crustal composition, geothermal gradientand partial melting to the velocity structure, which is characterized by low average crustalvelocities and widespread presence of low-velocity zone(s), the authors model the crustal velocityand density as functions of depth corresponding to various heat flow values in light of velocitymeasurements at high temperature and high pressure. The modeled velocity and density are regarded ascomparison standards. The comparison of the standards with seismic observations in southern Tibetimplies that the predominantly felsic composition at high heat flow cannot explain the observedvelocity structure there. Hence, the authors are in favor of attributing low average crustalvelocities and low-velocity zone(s) observed in southern Tibet mainly to partial melting. Modelingbased on the experimental results suggests that a melting percentage of 7-12 could account for thelow-velocity zone(s).展开更多
目的筛选康北高原慢性阻塞性肺疾病急性加重患者发生静脉血栓栓塞症风险的预测因素,建立AECOPD发生VTE风险的联合预测模型并分析其预测效能。方法选择2018年1月-2022年9月因慢性阻塞性肺疾病急性加重在甘孜县人民医院住院治疗的患者71例...目的筛选康北高原慢性阻塞性肺疾病急性加重患者发生静脉血栓栓塞症风险的预测因素,建立AECOPD发生VTE风险的联合预测模型并分析其预测效能。方法选择2018年1月-2022年9月因慢性阻塞性肺疾病急性加重在甘孜县人民医院住院治疗的患者71例,根据是否发生VTE分为血栓组35例,对照组36例。收集患者的基本资料和检查、检验资料等相关参数数据,选出两组之间具有显著差异的指标。将上述单因素分析中有显著差异的指标纳入多因素分析,筛选出AECOPD发生VTE风险的独立影响因素,并构建预测模型。利用受试者工作特征(receiver operating characteristic,ROC)曲线评价各独立因素及预测模型的应用价值,计算曲线下面积及其敏感度与特异度,分析其预测效能,霍斯默-莱梅肖检验评价拟合度。结果单因素分析显示血栓组PPS评分、乳酸脱氢酶(LDH)、D-二聚体、降钙素原(PCT)均高于对照组(均P<0.05)。Logistic回归分析显示PPS评分、乳酸脱氢酶(LDH)、D-二聚体为AECOPD发生VTE的独立预测因素。三者联合构建的预测模型曲线下面积(area under curve,AUC)为0.944(95%CI:0.893~0.996),灵敏度、特异度均明显优于各单一指标(灵敏度为94.3%、特异度为83.3%),霍斯默-莱梅肖检验拟合度好(χ^(2)=11.915,P=0.155)。结论PPS评分、乳酸脱氢酶(LDH)、D-二聚体可能是预测康北高原AECOPD发生VTE的因素,且三者联合构建的预测模型对VTE风险预测具有很好效能,可为预测AECOPD发生VTE的风险提供参考。展开更多
基金supported by the National Natural Science Foundation of China (91131905, 30890030)Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13020500)Weng Hongwu Original Scientific Research Foundation, Peking University
文摘Humans have been exposed to many environmental challenges since their evolutionary origins in Africa and subsequent migrations to the rest of the world. A severe environmental challenge to human migrants was hypoxia caused by low barometric oxygen pressure at high altitudes. Several genome-wide scans have elucidated the genetic basis of human high-altitude adaptations.However, the dearth of functional variant information has led to the successful association of only a few candidate genes. In the present study, we employed a candidate gene approach and re-sequenced the EDAR locus in 45 Tibetan individuals to identify mutations involved in hypoxia adaptation. We identified 10 and five quantitative trait-associated mutations for oxygen saturation (SaO_2) and blood platelet count, respectively, at the EDAR locus. Among these, rs10865026 and rs3749110 (associated with SaO_2 and platelet count, respectively) were identified as functional candidate targets. These data demonstrate that EDAR has undergone natural selection in recent human history and indicate an important role of EDAR variants in Tibetan high-altitude adaptations.
基金supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13010000)the National Natural Science Foundation of China(91631306 to BS,31671329 to XQ,31460287 to Ou,31501013 to HZ,and 31360032 to CC)+2 种基金the National 973 program(2012CB518202 to TW)the State Key Laboratory of Genetic Resources and Evolution(GREKF15-05,GREKF16-04)the Zhufeng Scholar Program of Tibetan University
文摘The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300 （histone acetyltransferase p300）, we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide （NO） concentration. Collectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.
文摘People living on the high plateaus of the world have long fascinated biological anthropologists and geneticists because they live in ＂thin air＂ and epitomize an extreme of human biological adaptation.
基金supported jointly by the National Natural Science Foundation of China(Grant No.91337216)the Special Fund for Public Welfare Industry(Meteorology),administered by the Chinese Ministry of Finance and the Ministry of Science and Technology(Grant No.GYHY201406001)the CAS XDA(Grant No.11010402)
文摘The impact of surface sensible heating over the Tibetan Plateau （SHTP） on the western Pacific subtropical high （WPSH） with and without air-sea interaction was investigated in this study. Data analysis indicated that SHTP acts as a relatively independent factor in modulating the WPSH anomaly compared with ENSO events. Stronger spring SHTP is usually fol- lowed by an enhanced and westward extension of the WPSH in summer, and vice versa. Numerical experiments using both an AGCM and a CGCM confirmed that SHTP influences the large-scale circulation anomaly over the Pacific, which features a barotropic anticyclonic response over the northwestern Pacific and a cyclonic response to the south. Owing to different background circulation in spring and summer, such a response facilitates a subdued WPSH in spring but an en- hanced WPSH in summer. Moreover, the CGCM results showed that the equatorial low-level westerly at the south edge of the cyclonic anomaly brings about a warm SST anomaly （SSTA） in the equatorial central Pacific via surface warm advection. Subsequently, an atmospheric Rossby wave is stimulated to the northwest of the warm SSTA, which in turn enhances the at- mospheric dipole anomalies over the western Pacific. Therefore, the air-sea feedbacks involved tend to reinforce the effect of SHTP on the WPSH anomaly, and the role of SHTP on general circulation needs to be considered in a land-air-sea interaction framework.
基金the Chinese Academy of Sciences(ZKCX2-SW-210)the National Natural Science Foundation of China under Grant Nos.40175021 and 40233037.
文摘The evident effects of the thermal anomalies over the Tibetan Plateau (TP) and its vicinities are summarized and discussed in this paper. By the singular value decomposition (SVD) technique and numerical simulations of the effect of the snow depth anomaly over the TP, it is shown that the snow depth anomaly, especially in winter, is one of the factors innuencing precipitation in China, and the winter snow anomaly is more important than the spring one. The relations between the sensible heat anomaly over the TP and the intensity of the South China Sea summer monsoon (SCSSM) are studied, too, and two key areas of the sensible heat anomaly over the TP are found. The relationships between the South Asia High (SAH) and the precipitation in the years with typical droughts or floods in the mid to lower valleys of the Yangtze River (MLVYR) and North China are investigated in some detail. It is found that not only the intensity of the SAH over the TP, but also the 100-hPa height in a large area influences the precipitation in the above two regions. The effects of the SAH on the onsets of the tropical Asian summer monsoon (TASM) including the SCSSM and the tropical Indian summer monsoon (TISM) are studied as well. It is found that the onset times of both the SCSSM and the TISM are highly dependent upon the latitudinal position of the SAH center.
文摘Allelic variation and genetic diversity at HMW glutenin subunits loci, Glu-A1, Glu-B1and Glu-D1 were investigated in 64 accessions of three unique wheats of western Chinausing sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Two HMWglutenin patterns (i.e., null, 7+8, 2+12 and null, 7, 2+12) in 34 Yunnan wheataccessions, 3 HMW glutenin patterns (i.e., null, 7+8, 2+12; null, 6+8, 2+12 andnull, 7+8, 2) in 24 Tibetan accessions and 1 HMW glutenin pattern (null, 7, 2+12) in6 Xinjiang wheat accessions were found. The Tibetan accession TB18 was found to be witha rare subunit 2 encoded by Glu-D1. A total of 4 (i.e., Glu-A1c, Glu-B1a, Glu-B1b andGlu-D1a), 5 (i.e., Glu-A1c, Glu-B1d, Glu-B1b, Glu-D1a and Glu-D1) and 3 alleles (i.e.,Glu-A1c, Glu-B1a and Glu-D1a) at Glu-1 locus were identified among Yunnan, Tibetan andXinjiang unique wheat accessions, respectively. For Yunnan wheat, Tibetan wheat andXinjiang wheat, the Neis mean genetic variation indexes were 0.1574, 0.1366 and 0,respectively, which might indicate the higher genetic diversity at HMW glutenin subunitsloci of Yunnan and Tibetan wheat accessions as compared to that of Xinjiang wheataccessions. Among the three genomes of hexaploid wheats of western China, the highestNeis genetic variation index was appeared in B genome with the mean value of 0.2674,while the indexes for genomes A and D were 0 and 0.0270, respectively. It might bereasonable to indicate that Glu-B1 showed the highest, Glu-D1 the intermediate and Glu-A1 always the lowest genetic diversity.
基金supported by the Key Basic Research and Development Program of China(G19980407000)the National Natural Science Foundation of China(40072062)+1 种基金the Foundation of the Open Laboratory of Tectonophysics,China Seismological Bureauthe Post-Doctoral Grant of Ministry of Education,China.
文摘In order to constrain the crustal wave velocity structure in the southernTibetan crust and provide insight into the contribution of crustal composition, geothermal gradientand partial melting to the velocity structure, which is characterized by low average crustalvelocities and widespread presence of low-velocity zone(s), the authors model the crustal velocityand density as functions of depth corresponding to various heat flow values in light of velocitymeasurements at high temperature and high pressure. The modeled velocity and density are regarded ascomparison standards. The comparison of the standards with seismic observations in southern Tibetimplies that the predominantly felsic composition at high heat flow cannot explain the observedvelocity structure there. Hence, the authors are in favor of attributing low average crustalvelocities and low-velocity zone(s) observed in southern Tibet mainly to partial melting. Modelingbased on the experimental results suggests that a melting percentage of 7-12 could account for thelow-velocity zone(s).
文摘目的筛选康北高原慢性阻塞性肺疾病急性加重患者发生静脉血栓栓塞症风险的预测因素,建立AECOPD发生VTE风险的联合预测模型并分析其预测效能。方法选择2018年1月-2022年9月因慢性阻塞性肺疾病急性加重在甘孜县人民医院住院治疗的患者71例,根据是否发生VTE分为血栓组35例,对照组36例。收集患者的基本资料和检查、检验资料等相关参数数据,选出两组之间具有显著差异的指标。将上述单因素分析中有显著差异的指标纳入多因素分析,筛选出AECOPD发生VTE风险的独立影响因素,并构建预测模型。利用受试者工作特征(receiver operating characteristic,ROC)曲线评价各独立因素及预测模型的应用价值,计算曲线下面积及其敏感度与特异度,分析其预测效能,霍斯默-莱梅肖检验评价拟合度。结果单因素分析显示血栓组PPS评分、乳酸脱氢酶(LDH)、D-二聚体、降钙素原(PCT)均高于对照组(均P<0.05)。Logistic回归分析显示PPS评分、乳酸脱氢酶(LDH)、D-二聚体为AECOPD发生VTE的独立预测因素。三者联合构建的预测模型曲线下面积(area under curve,AUC)为0.944(95%CI:0.893~0.996),灵敏度、特异度均明显优于各单一指标(灵敏度为94.3%、特异度为83.3%),霍斯默-莱梅肖检验拟合度好(χ^(2)=11.915,P=0.155)。结论PPS评分、乳酸脱氢酶(LDH)、D-二聚体可能是预测康北高原AECOPD发生VTE的因素,且三者联合构建的预测模型对VTE风险预测具有很好效能,可为预测AECOPD发生VTE的风险提供参考。
