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Hao L.-M.,Tsinghua University | Lu J.-K.,Zhengzhou University | Zhang Y.-S.,Tianjin Polytechnic University | Wu T.-Y.,High Altitude Medical Research Institute
Journal of Food Processing and Preservation | Year: 2013

In this study, the functional properties of Jxsac, a recently developed high-molecular-weight polysaccharide product, have been characterized. The physicochemical properties (such as its composition, transparency, retrogradation and blue value), solution viscosity, infrared spectroscopy and gel filtration chromatography of Jxsac were characterized in comparison with that of Vitargo polysaccharide, a commercially available product for sports drinks, and that of corn starch. The results showed that the properties of Jxsac were comparable to, but significantly different from, that of Vitargo polysaccharide. The molecular weight of Jxsac is about 288.1kDa compared with 303.5kDa for Vitargo polysaccharide. Thin layer chromatography result of the hydrolysate showed that the basic component of Jxsac was glucose. The results from this work demonstrated that Jxsac could be a desirable alternative as a key ingredient for the formulation of high-energy solid beverage. PRACTICAL APPLICATIONS: Polysaccharides are important structural ingredients of sports drinks. This study developed a new polysaccharide named Jxsac, having excellent functionalities as a key ingredient in the production of high-energy solid beverages. Moreover, Jxsac has a short production time with low cost, so it has a special advantage in the industrial application of sports drinks. © 2012 Wiley Periodicals, Inc.


PubMed | Peoples Hospital of Dangxiong County, Tibetan University, High Altitude Medical Research Institute, CAS Kunming Institute of Zoology and 4 more.
Type: | Journal: Molecular biology and evolution | Year: 2017

Tibetans are well adapted to the hypoxic environments at high altitude, yet the molecular mechanism of this adaptation remains elusive. We reported comprehensive genetic and functional analyses of EPAS1, a gene encoding hypoxia inducible factor 2 (HIF-2) with the strongest signal of selection in previous genome-wide scans of Tibetans. We showed that the Tibetan-enriched EPAS1 variants down-regulate expression in human umbilical endothelial cells and placentas. Heterozygous EPAS1 knockout mice display blunted physiological responses to chronic hypoxia, mirroring the situation in Tibetans. Furthermore, we found that the Tibetan version of EPAS1 is not only associated with the relatively low hemoglobin level as a polycythemia protectant, but also is associated with a low pulmonary vasoconstriction response in Tibetans. We propose that the down-regulation of EPAS1 contributes to the molecular basis of Tibetans adaption to high-altitude hypoxia.


PubMed | CAS Beijing Institute of Genomics, High Altitude Medical Research Institute, CAS Kunming Institute of Zoology, The Municipal Peoples Hospital of Lhasa and Tibetan University
Type: Journal Article | Journal: Human mutation | Year: 2016

Tibetans are well adapted to high-altitude environments. Among the adaptive traits in Tibetans, the relatively low hemoglobin level is considered a blunted erythropoietic response to hypoxic challenge. Previously, EPAS1 and EGLN1, the major upstream regulators in the hypoxic pathway, were reportedly involved in the hemoglobin regulation in Tibetans. In this study, we report a downstream gene (HMOX2) involved in heme catabolism, which harbors potentially adaptive variants in Tibetans. We first resequenced the entire genomic region (45.6 kb) of HMOX2 in Tibetans, which confirmed the previously suspected signal of positive selection on HMOX2 in Tibetans. Subsequent association analyses of hemoglobin levels in two independent Tibetan populations (a total of 1,250 individuals) showed a male-specific association between the HMOX2 variants and hemoglobin levels. Tibetan males with the derived C allele at rs4786504:T>C displayed lower hemoglobin level as compared with the T allele carriers. Furthermore, our in vitro experiments indicated that the C allele of rs4786504 could increase the expression of HMOX2, presumably leading to a more efficient breakdown of heme that may help maintain a relatively low hemoglobin level at high altitude. Collectively, we propose that HMOX2 contributes to high-altitude adaptation in Tibetans by functioning as a modifier in the regulation of hemoglobin metabolism.


Hao L.-M.,Tsinghua University | Hao L.-M.,Quartermaster Research Institute | Xing X.-H.,Tsinghua University | Li Z.,Beijing University of Chemical Technology | And 6 more authors.
Applied Biochemistry and Biotechnology | Year: 2010

This paper is concerned with the optimization of effect factors for mycelial growth and exopolysaccharide production by Schizophyllum commune by one-factor-at-a-time and orthogonal methods. The one-factor-at-a-time method was adopted to investigate the effects of six different compounds (sodium carboxymethylcellulose, l-glutamic acid, VB1, naphthalene acetic acid, oleic acid, and Tween 80) on mycelial growth and exopolysaccharide production. Among these factors, oleic acid, VB1 and Tween 80 were identified to be the most important factors. Subsequently, the concentration of oleic acid, VB1 and Tween 80 were optimized using the orthogonal matrix method. The effects of the factors on the mycelial growth of S. commune were in the order of oleic acid>VB1>Tween 80, and those on exopolysaccharide production were in the same order. The optimal concentration for mycelia and exopolysaccharide were determined as oleic acid 0.1% (v/v), VB1 0.5 mg/L, and Tween 80 6 mg/L. The subsequent verification experiments confirmed the validity of the models. Under this optimized conditions in shake flask culture, the mycelial yield and exo-biopolymer production were 25.93 and 2.79 g/L, respectively, which were considerably higher than those obtained in the preliminary studies. The result was further confirmed in a 7-L fermentor experiments. © 2009 Humana Press.


Wu T.-Y.,High Altitude Medical Research Institute | Ding S.-Q.,Qinghai Tibet Railroad Hospital at Fenghuoshan | Liu J.-L.,Qinghai Tibet Railroad Hospital at Kekexili | Jia J.-H.,Qinghai Tibet Railroad Hospital at Fenghuoshan | And 2 more authors.
Chinese Medical Journal | Year: 2012

Background It is important to determine the incidence of acute mountain sickness (AMS) among workers at altitudes between 3500 m and 5000 m on Mt. Tanggula during the construction of the Qinghai-Tibet railroad. This study explored the risk factors predisposing workers to developing AMS and attempted to develop more effective ways of preventing and treating AMS. Methods A total of 11 182 workers were surveyed by completing twice daily a Lake Louise questionnaire, and a score ≥3 indicated AMS. The contributing risk factors were assessed for at least 2 months for the duration of the study in the years from 2001 to 2003. A risk model was developed by multiple Logistic regression. Standard statistical methods were used to analyze data. Results AMS occurred in 56% of workers working at high altitudes on Mt. Tanggula. The incidence of AMS increased with increasing altitude. Rapid ascent to an altitude above 3500 m, sea-level or lowland newcomers, young people under 25 years of age, heavy physical exertion, obese person, and arterial oxygen saturation (SaO 2) below 80% were independent AMS risk factors. No significant association was found between AMS and sex or taking Rhodiola. Medical education contributed to an early diagnosis of AMS. Conclusions This study used the Lake Louise scoring system suggesting that it is a well-validated standard for field evaluation of AMS and for making an early diagnosis. These studies have described many variables regarding risk factors for the development of AMS. Risk factors which can be modified should be attended to, and the physicians should carry out check-ups and tests to identify subjects who are more at risk. Prevention consists in continuous gradual ascent, medical education, and prompt descent to avoid progression in patients with serious AMS. It is most important to effectively control the risk factors of AMS.


Qi X.,CAS Kunming Institute of Zoology | Cui C.,Tibetan University | Peng Y.,CAS Kunming Institute of Zoology | Peng Y.,University of Chinese Academy of Sciences | And 22 more authors.
Molecular Biology and Evolution | Year: 2013

Tibetans live on the highest plateau in the world, their current population size is approximately 5 million, and most of them live at an altitude exceeding 3,500 m. Therefore, the Tibetan Plateau is a remarkable area for cultural and biological studies of human population history. However, the chronological profile of the Tibetan Plateau's colonization remains an unsolved question of human prehistory. To reconstruct the prehistoric colonization and demographic history of modern humans on the Tibetan Plateau, we systematically sampled 6,109 Tibetan individuals from 41 geographic populations across the entire region of the Tibetan Plateau and analyzed the phylogeographic patterns of both paternal (n= 2,354) and maternal (n= 6,109) lineages as well as genome-wide single nucleotide polymorphism markers (n = 50) in Tibetan populations. We found that there have been two distinct, major prehistoric migrations of modern humans into the Tibetan Plateau. The first migration was marked by ancient Tibetan genetic signatures dated to approximately 30,000 years ago, indicating that the initial peopling of the Tibetan Plateau by modern humans occurred during the Upper Paleolithic rather than Neolithic. We also found evidences for relatively young (only 7-10 thousand years old) shared Y chromosome and mitochondrial DNA haplotypes between Tibetans and Han Chinese, suggesting a second wave of migration during the early Neolithic. Collectively, the genetic data indicate that Tibetans have been adapted to a high altitude environment since initial colonization of the Tibetan Plateau in the early Upper Paleolithic, before the last glacial maximum, followed by a rapid population expansion that coincided with the establishment of farming and yak pastoralism on the Plateau in the early Neolithic. © The Author 2013.


Peng Y.,CAS Kunming Institute of Zoology | Peng Y.,University of Chinese Academy of Sciences | Yang Z.,CAS Kunming Institute of Zoology | Yang Z.,University of Chinese Academy of Sciences | And 13 more authors.
Molecular Biology and Evolution | Year: 2011

Modern humans have occupied almost all possible environments globally since exiting Africa about 100,000 years ago. Both behavioral and biological adaptations have contributed to their success in surviving the rigors of climatic extremes, including cold, strong ultraviolet radiation, and high altitude. Among these environmental stresses, high-altitude hypoxia is the only condition in which traditional technology is incapable of mediating its effects. Inhabiting at >3,000-m high plateau, the Tibetan population provides a widely studied example of high-altitude adaptation. Yet, the genetic mechanisms underpinning long-term survival in this environmental extreme remain unknown. We performed an analysis of genome-wide sequence variations in Tibetans. In combination with the reported data, we identified strong signals of selective sweep in two hypoxia-related genes, EPAS1 and EGLN1. For these two genes, Tibetans show unusually high divergence from the non-Tibetan lowlanders (Han Chinese and Japanese) and possess high frequencies of many linked sequence variations as reflected by the Tibetan-specific haplotypes. Further analysis in seven Tibetan populations (1,334 individuals) indicates the prevalence of selective sweep across the Himalayan region. The observed indicators of natural selection on EPAS1 and EGLN1 suggest that during the long-term occupation of high-altitude areas, the functional sequence variations for acquiring biological adaptation to high-altitude hypoxia have been enriched in Tibetan populations. © 2010 The Author.


Xiang K.,CAS Kunming Institute of Zoology | Xiang K.,University of Chinese Academy of Sciences | Ouzhuluobu,Tibetan University | Peng Y.,CAS Kunming Institute of Zoology | And 18 more authors.
Molecular Biology and Evolution | Year: 2013

Tibetans are well adapted to high-altitude hypoxic conditions, and in recent genome-wide scans, many candidate genes have been reported involved in the physiological response to hypoxic conditions. However, the limited sequence variations analyzed in previous studies would not be sufficient to identify causal mutations. Here we conducted resequencing of the entire genomic region (59.4 kb) of the hypoxic gene EGLN1 (one of the top candidates from the genome-wide scans) in Tibetans and identified 185 sequence variations, including 13 novel variations (12 substitutions and 1 insertion or deletion). There is a nonsynonymous mutation (rs186996510, D4E) showing surprisingly deep divergence between Tibetans and lowlander populations (FST = 0.709 between Tibetans and Han Chinese). It is highly prevalent in Tibetans (70.9% on average) but extremely rare in Han Chinese, Japanese, Europeans, and Africans (0.56-2.27%), suggesting that it might be the causal mutation of EGLN1 contributing to high-altitude hypoxic adaptation. Neutrality test confirmed the signal of Darwinian positive selection on EGLN1 in Tibetans. Haplotype network analysis revealed a Tibetan-specific haplotype, which is absent in other world populations. The estimated selective intensity (0.029 for the C allele of rs186996510) puts EGLN1 among the known genes that have undergone the strongest selection in human populations, and the onset of selection was estimated to have started at the early Neolithic (∼8,400 years ago). Finally, we detected a significant association between rs186996510 and hemoglobin levels in Tibetans, suggesting that EGLN1 contributes to the adaptively low hemoglobin level of Tibetans compared with acclimatized lowlanders at high altitude. © The Author 2013.


Wu T.-Y.,Physiological Research Group of the Ministry of Railroad | Wu T.-Y.,High Altitude Medical Research Institute | Wu T.-Y.,Tibet University | Ding S.-Q.,Qingai Tibet Railroad Hospitals of the Construction Company | And 7 more authors.
Thorax | Year: 2012

Rationale: The relationship between cigarette smoking and acute mountain sickness (AMS) is not clear. Objective: To assess AMS risk and altitude acclimatisation in relation to smoking. Methods: 200 healthy non-smokers and 182 cigarette smokers were recruited from Han lowland workers. These were men without prior altitude exposure, matched for age, health status and occupation, who were transported to an altitude of 4525 masl. Measurements: AMS, smoking habits, arterial saturation (SpO2), haemoglobin (Hb), lung function and mean pulmonary artery pressure (PAPm) were assessed upon arrival and after 3 and 6 months. Main results: Compared with non-smokers, smokers had a lower incidence of AMS and lower AMS scores than non-smokers upon arrival; higher Hb and PAPm associated with lower SpO2 at 3 and 6 months at altitude; and lower forced expiratory volume in 1 s and maximal voluntary ventilation at 3 and 6 months. Conclusions: Smoking slightly decreases the risk of AMS but impairs long-term altitude acclimatisation and lung function during a prolonged stay at high altitude.


PubMed | High Altitude Medical Research Institute, CAS Kunming Institute of Zoology and Tibetan University
Type: | Journal: Scientific reports | Year: 2015

Sherpas living around the Himalayas are renowned as high-altitude mountain climbers but when and where the Sherpa people originated from remains contentious. In this study, we collected DNA samples from 582 Sherpas living in Nepal and Tibet Autonomous Region of China to study the genetic diversity of both their maternal (mitochondrial DNA) and paternal (Y chromosome) lineages. Analysis showed that Sherpas share most of their paternal and maternal lineages with indigenous Tibetans, representing a recently derived sub-lineage. The estimated ages of two Sherpa-specific mtDNA sub-haplogroups (C4a3b1 and A15c1) indicate a shallow genetic divergence between Sherpas and Tibetans less than 1,500 years ago. These findings reject the previous theory that Sherpa and Han Chinese served as dual ancestral populations of Tibetans, and conversely suggest that Tibetans are the ancestral populations of the Sherpas, whose adaptive traits for high altitude were recently inherited from their ancestors in Tibet.

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