Adaptation and Mal-Adaptation to Ambient Hypoxia; Andean, Ethiopian and Himalayan Patterns
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{"title"=>"Adaptation and mal-adaptation to ambient hypoxia; Andean, Ethiopian and Himalayan patterns", "type"=>"journal", "authors"=>[{"first_name"=>"Guoqiang", "last_name"=>"Xing", "scopus_author_id"=>"55550498800"}, {"first_name"=>"Clifford", "last_name"=>"Qualls", "scopus_author_id"=>"35494568200"}, {"first_name"=>"Luis", "last_name"=>"Huicho", "scopus_author_id"=>"55915133100"}, {"first_name"=>"Maria", "last_name"=>"River-Ch", "scopus_author_id"=>"24491296400"}, {"first_name"=>"Tsering", "last_name"=>"Stobdan", "scopus_author_id"=>"56062229800"}, {"first_name"=>"Marat", "last_name"=>"Slessarev", "scopus_author_id"=>"12760480700"}, {"first_name"=>"Eitan", "last_name"=>"Prisman", "scopus_author_id"=>"16417775300"}, {"first_name"=>"Soji", "last_name"=>"Ito", "scopus_author_id"=>"24490910800"}, {"first_name"=>"Hong", "last_name"=>"Wu", "scopus_author_id"=>"57198665541"}, {"first_name"=>"Angchuk", "last_name"=>"Norboo", "scopus_author_id"=>"24491334000"}, {"first_name"=>"Diskit", "last_name"=>"Dolma", "scopus_author_id"=>"24576732400"}, {"first_name"=>"Moses", "last_name"=>"Kunzang", "scopus_author_id"=>"24490916100"}, {"first_name"=>"Tsering", "last_name"=>"Norboo", "scopus_author_id"=>"6603034167"}, {"first_name"=>"Jorge L.", "last_name"=>"Gamboa", "scopus_author_id"=>"7004524699"}, {"first_name"=>"Victoria E.", "last_name"=>"Claydon", "scopus_author_id"=>"6506256529"}, {"first_name"=>"Joseph", "last_name"=>"Fisher", "scopus_author_id"=>"7404016379"}, {"first_name"=>"Guta", "last_name"=>"Zenebe", "scopus_author_id"=>"6506772334"}, {"first_name"=>"Amha", "last_name"=>"Gebremedhin", "scopus_author_id"=>"14321430200"}, {"first_name"=>"Roger", "last_name"=>"Hainsworth", "scopus_author_id"=>"7007040180"}, {"first_name"=>"Ajay", "last_name"=>"Verma", "scopus_author_id"=>"7401937982"}, {"first_name"=>"Otto", "last_name"=>"Appenzeller", "scopus_author_id"=>"7006367369"}], "year"=>2008, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"352102888", "sgr"=>"48649103572", "issn"=>"19326203", "arxiv"=>"65", "pmid"=>"18523639", "scopus"=>"2-s2.0-48649103572", "doi"=>"10.1371/journal.pone.0002342", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"75dc0277-1c9c-3499-9ee3-a1821bef7b07", "abstract"=>"The study of the biology of evolution has been confined to laboratories and model organisms. However, controlled laboratory conditions are unlikely to model variations in environments that influence selection in wild populations. Thus, the study of \"fitness\" for survival and the genetics that influence this are best carried out in the field and in matching environments. Therefore, we studied highland populations in their native environments, to learn how they cope with ambient hypoxia. The Andeans, African highlanders and Himalayans have adapted differently to their hostile environment. Chronic mountain sickness (CMS), a loss of adaptation to altitude, is common in the Andes, occasionally found in the Himalayas; and absent from the East African altitude plateau. We compared molecular signatures (distinct patterns of gene expression) of hypoxia-related genes, in white blood cells (WBC) from Andeans with (n = 10), without CMS (n = 10) and sea-level controls from Lima (n = 20) with those obtained from CMS (n = 8) and controls (n = 5) Ladakhi subjects from the Tibetan altitude plateau. We further analyzed the expression of a subset of these genes in Ethiopian highlanders (n = 8). In all subjects, we performed the studies at their native altitude and after they were rendered normoxic. We identified a gene that predicted CMS in Andeans and Himalayans (PDP2). After achieving normoxia, WBC gene expression still distinguished Andean and Himalayan CMS subjects. Remarkably, analysis of the small subset of genes (n = 8) studied in all 3 highland populations showed normoxia induced gene expression changes in Andeans, but not in Ethiopians nor Himalayan controls. This is consistent with physiologic studies in which Ethiopians and Himalayans show a lack of responsiveness to hypoxia of the cerebral circulation and of the hypoxic ventilatory drive, and with the absence of CMS on the East African altitude plateau.", "link"=>"http://www.mendeley.com/research/adaptation-maladaptation-ambient-hypoxia-andean-ethiopian-himalayan-patterns", "reader_count"=>69, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>6, "Librarian"=>1, "Researcher"=>14, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>1, "Student > Master"=>7, "Other"=>1, "Student > Bachelor"=>8, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>10}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>6, "Librarian"=>1, "Researcher"=>14, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>1, "Student > Master"=>7, "Other"=>1, "Student > Bachelor"=>8, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>10}, "reader_count_by_subject_area"=>{"Unspecified"=>7, "Agricultural and Biological Sciences"=>27, "Arts and Humanities"=>1, "Chemistry"=>1, "Earth and Planetary Sciences"=>1, "Economics, Econometrics and Finance"=>1, "Environmental Science"=>3, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>19, "Neuroscience"=>1, "Sports and Recreations"=>2, "Psychology"=>1, "Social Sciences"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>19}, "Social Sciences"=>{"Social Sciences"=>3}, "Sports and Recreations"=>{"Sports and Recreations"=>2}, "Psychology"=>{"Psychology"=>1}, "Unspecified"=>{"Unspecified"=>7}, "Environmental Science"=>{"Environmental Science"=>3}, "Arts and Humanities"=>{"Arts and Humanities"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Neuroscience"=>{"Neuroscience"=>1}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>27}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}}, "reader_count_by_country"=>{"United States"=>3, "Switzerland"=>1, "Peru"=>1, "Germany"=>1, "Spain"=>3}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/930411"], "description"=>"<p>To assess the impact of specific genes on chronic mountain sickness-score (CMS-sc), using a sliding scale (continuous), we show an “impact table” for the combined (CMS & Controls) Himalayan (Ladakh) groups at native altitude after 1 hour of hyperoxia <b>(B)</b>. The best predictor, under these circumstances, is <b>PDK4</b>.</p><p>In univariate linear regression model, <b>PDK4</b> is found to be the most significant predictor of CMS-sc (highlighted). Adjusting for PDK4 eliminates the impact of the other genes on the CMS-sc (columns, ADJ for PDK4). However, adjusting PDK4 for each of the remaining genes, assayed here, strengthens the impact of PDK4 (columns, Adj.PDK4). This supports the importance of PDK4 in predicting CMS-sc in the Himalayas under conditions of hyperoxia just as in the Andes in normoxia, see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002342#pone-0002342-t003\" target=\"_blank\">Table 3</a>, (For glossary of terms, see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002342#pone-0002342-t002\" target=\"_blank\">table 2</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002342#pone.0002342.s001\" target=\"_blank\">Text S1</a>).</p><p><b>PDK4</b> (pyruvate dehydrogenase Kinase 4) is a kinase involved in “aerobic glycolysis” (the Warburg effect). It supports a metabolic pattern seen in many (but not all) hypoxia adapted tissues, also in cancer cells and activated immune cells.</p>", "links"=>[], "tags"=>["predicting", "hypoxia-related", "genes", "cms", "himalayas", "altitude", "4450"], "article_id"=>600837, "categories"=>["Molecular Biology", "Physiology", "Medicine", "Evolutionary Biology"], "users"=>["Guoqiang Xing", "Clifford Qualls", "Luis Huicho", "Maria River-Ch", "Tsering Stobdan", "Marat Slessarev", "Eitan Prisman", "Soji Ito", "Hong Wu", "Angchuk Norboo", "Diskit Dolma", "Moses Kunzang", "Tsering Norboo", "Jorge L. Gamboa", "Victoria E. Claydon", "Joseph Fisher", "Guta Zenebe", "Amha Gebremedhin", "Roger Hainsworth", "Ajay Verma", "Otto Appenzeller"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002342.t005", "stats"=>{"downloads"=>4, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impact_table_to_show_the_predicting_power_of_specific_hypoxia_related_genes_on_CMS_CMS_score_8805_12_in_the_Himalayas_Korzok_village_altitude_4450_m_after_1_hour_of_hyperoxia_/600837", "title"=>"Impact table to show the predicting power of specific hypoxia-related genes on CMS (CMS-score≥12) in the Himalayas (Korzok village altitude 4450 m.) after 1 hour of hyperoxia.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-06-04 00:13:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/929951"], "description"=>"<p>A. Controls in Peru altitude 4338 m. and Himalyan controls, on the Tibetan plateau in Ladakh, India, altitude 4450 m. B. CMS patients at the same altitudes as in A in Peru and in the Himalayas. C. Peruvian and Himalayan controls in normoxia. D. Peruvian and Himalayan CMS patients in normoxia. The genes compared in the 2 populations are: 1 = HIF-1a; 2 = HPH3; 3 = HIF-3a; 4 = VEGFC; 5 = PDK4; 6 = HIF2a; 7 = PDP2; 8 = PDK1; 9 = PDHE1a1; 10 = EPOR; 11 = PDP1; 12 = PDK3; 13 = HIF1b; 14 = PDK2; 15 = GLUT1; 16 = GAPDH; 17 = HPH1; 18 = EPO; 19 = HPH2. Interrupted lines span across genes not assayed. In ambient hypoxia all Himalayans (controls and CMS) had significantly higher gene expression when compared to Andeans except for HPH1. The differences between the groups, while normoxic, were not significant. (C. D.).</p>", "links"=>[], "tags"=>["comparisons", "andean", "himalayan", "altitude"], "article_id"=>600369, "categories"=>["Molecular Biology", "Physiology", "Medicine", "Evolutionary Biology"], "users"=>["Guoqiang Xing", "Clifford Qualls", "Luis Huicho", "Maria River-Ch", "Tsering Stobdan", "Marat Slessarev", "Eitan Prisman", "Soji Ito", "Hong Wu", "Angchuk Norboo", "Diskit Dolma", "Moses Kunzang", "Tsering Norboo", "Jorge L. Gamboa", "Victoria E. Claydon", "Joseph Fisher", "Guta Zenebe", "Amha Gebremedhin", "Roger Hainsworth", "Ajay Verma", "Otto Appenzeller"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002342.g003", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantitative_comparisons_of_gene_expression_in_Andean_and_Himalayan_altitude_dwellers_/600369", "title"=>"Quantitative comparisons of gene expression in Andean and Himalayan altitude dwellers.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-06-04 00:06:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/930167"], "description"=>"<p>The subjects were exposed to hyperoxia for 1 hour. Note the venous catheters in place on the forearms to allow the drawing of blood for the post hyperoxia samples. This maneuver resulted in significant changes in gene expression in white blood cells.</p>", "links"=>[], "tags"=>["4450", "tibetan", "korzok"], "article_id"=>600588, "categories"=>["Molecular Biology", "Physiology", "Medicine", "Evolutionary Biology"], "users"=>["Guoqiang Xing", "Clifford Qualls", "Luis Huicho", "Maria River-Ch", "Tsering Stobdan", "Marat Slessarev", "Eitan Prisman", "Soji Ito", "Hong Wu", "Angchuk Norboo", "Diskit Dolma", "Moses Kunzang", "Tsering Norboo", "Jorge L. Gamboa", "Victoria E. Claydon", "Joseph Fisher", "Guta Zenebe", "Amha Gebremedhin", "Roger Hainsworth", "Ajay Verma", "Otto Appenzeller"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002342.g006", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hyperoxia_in_a_tent_at_4450_m_on_the_Tibetan_plateau_near_Korzok_village_in_Ladakh_India_/600588", "title"=>"Hyperoxia in a tent at 4450 m. on the Tibetan plateau, near Korzok village in Ladakh, India.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-06-04 00:09:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/929814"], "description"=>"<p>Because LDHA was not assayed at altitude it was substituted by PDK3 which was highly correlated with LDHA. A: CMS vs CP Controls in Lima (normoxia). B: Lima Controls vs CP Controls in Lima. C: CMS vs CP Controls in Cerro de Pasco (4338 m,). When hypoxia was shown to have been replaced by short sea level sojourn, normoxia (A), the CMS patients were clearly separated from control altitude dwellers. B. There were no differences between altitude controls and Lima controls in Lima. In Cerro de Pasco the CMS patients and controls were mostly separated by the “discriminator line”. Discriminator line based on discrimination of the two groups by logistic regression. CMS = chronic mountain sickness. LDHA = Lactate dehydrogenase A. PDK3 = . Pyruvate dehydrogenase Kinase3. This kinase is involved in “aerobic glycolysis” (the Warburg effect). It suports a metabolic pattern seen in many (but not all) hypoxia adapted tissue, also in cancer cells and activated immune cells. PDP2 = phosphatase that de-phosphorylates the E1-alpha subunit of pyruvate dehydrogenase. CP = Cerro de Pasco altitude 4338 m. Cerro = Cerro de Pasco. Con = Andean controls. H = high altitude. L = Low altitude</p>", "links"=>[], "tags"=>["genes", "cms", "peruvian", "altitude"], "article_id"=>600237, "categories"=>["Molecular Biology", "Physiology", "Medicine", "Evolutionary Biology"], "users"=>["Guoqiang Xing", "Clifford Qualls", "Luis Huicho", "Maria River-Ch", "Tsering Stobdan", "Marat Slessarev", "Eitan Prisman", "Soji Ito", "Hong Wu", "Angchuk Norboo", "Diskit Dolma", "Moses Kunzang", "Tsering Norboo", "Jorge L. Gamboa", "Victoria E. Claydon", "Joseph Fisher", "Guta Zenebe", "Amha Gebremedhin", "Roger Hainsworth", "Ajay Verma", "Otto Appenzeller"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002342.g001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Niche_scatter_plots_of_genes_that_best_predict_the_presence_of_CMS_in_Peruvian_altitude_dwellers_/600237", "title"=>"Niche (scatter) plots of genes that best predict the presence of CMS in Peruvian altitude dwellers.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-06-04 00:03:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/930295"], "description"=>"<p>To assess the impact of specific genes on chronic mountain sickness-score (CMS-sc), using a sliding scale (continuous), we constructed an “impact table” for the combined (CMS & Controls) Cerro de Pasco groups while normoxic in Lima (sea level) (<b>B</b>).</p><p>In univariate linear regression model, <b>PDP2</b> is found to be the most significant predictor of CMS-sc (highlighted) even in normoxia. Adjusting for <b>PDP2</b> eliminates the impact of the other genes on the CMS-sc (columns, ADJ for PDP2). However, adjusting PDP2 for each of the remaining genes, assayed here, strengthens the impact of PDP2 (columns, Adj. PDP2). This supports the importance of <b>PDP2</b> in predicting the CMS-scores of our subjects while in Cerro de Pasco at altitude. (For glossary of terms see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002342#pone-0002342-t002\" target=\"_blank\">table 2</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002342#pone.0002342.s001\" target=\"_blank\">Text S1</a>).</p>", "links"=>[], "tags"=>["predicting", "hypoxia-related", "genes", "cms", "andean", "subjects", "altitude", "150"], "article_id"=>600717, "categories"=>["Molecular Biology", "Physiology", "Medicine", "Evolutionary Biology"], "users"=>["Guoqiang Xing", "Clifford Qualls", "Luis Huicho", "Maria River-Ch", "Tsering Stobdan", "Marat Slessarev", "Eitan Prisman", "Soji Ito", "Hong Wu", "Angchuk Norboo", "Diskit Dolma", "Moses Kunzang", "Tsering Norboo", "Jorge L. Gamboa", "Victoria E. Claydon", "Joseph Fisher", "Guta Zenebe", "Amha Gebremedhin", "Roger Hainsworth", "Ajay Verma", "Otto Appenzeller"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002342.t003", "stats"=>{"downloads"=>3, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impact_table_to_show_the_predicting_power_of_specific_hypoxia_related_genes_on_CMS_CMS_score_8805_12_in_our_Andean_subjects_in_Lima_Peru_altitude_150_m_/600717", "title"=>"Impact table to show the predicting power of specific hypoxia-related genes on CMS (CMS-score≥12) in our Andean subjects in Lima, Peru, altitude 150 m.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-06-04 00:11:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/929883"], "description"=>"<p>A. CMS vs Controls in Himalayans (Ladakh) at native altitude and ambient conditions at 4450 m. and at the same altitude after 1 hour of hyperoxia (B). A. In Korzok village, Ladakh, the CMS patients and controls were clearly separated by the “discriminator line”. B. When ambient hypoxia was shown to have been replaced by induced normoxia, the CMS patients were still separated from control altitude dwellers, although the best predictors for CMS had changed. Discriminator line based on discrimination of the two groups by logistic regression. CMS = chronic mountain sickness. PDK4 = . Pyruvate dehydrogenase Kinase 4. This kinase is involved in “aerobic glycolysis” (the Warburg effect).It supports a metabolic pattern seen in many (but not all) hypoxia adapted tissue, also in cancer cells and activated immune cells. PDP2 = phosphatase that de-phosphorylates the E1-alpha subunit of pyruvate dehydrogenase. HIF1a, HIF2a, HIF3a, HIF1b = Hypoxia Inducible Factors, composed of alpha and beta subunits. Only the alpha subunit protein levels are regulated by oxygen. HIF1b is used as a dimerizing partner by all three HIF1a's.</p>", "links"=>[], "tags"=>["genes", "cms", "himalayan", "altitude"], "article_id"=>600304, "categories"=>["Molecular Biology", "Physiology", "Medicine", "Evolutionary Biology"], "users"=>["Guoqiang Xing", "Clifford Qualls", "Luis Huicho", "Maria River-Ch", "Tsering Stobdan", "Marat Slessarev", "Eitan Prisman", "Soji Ito", "Hong Wu", "Angchuk Norboo", "Diskit Dolma", "Moses Kunzang", "Tsering Norboo", "Jorge L. Gamboa", "Victoria E. Claydon", "Joseph Fisher", "Guta Zenebe", "Amha Gebremedhin", "Roger Hainsworth", "Ajay Verma", "Otto Appenzeller"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002342.g002", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Niche_scatter_plots_of_genes_that_best_predict_the_presence_of_CMS_in_Himalayan_altitude_dwellers_/600304", "title"=>"Niche (scatter) plots of genes that best predict the presence of CMS in Himalayan altitude dwellers.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-06-04 00:05:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/458366"], "description"=>"<div><p>The study of the biology of evolution has been confined to laboratories and model organisms. However, controlled laboratory conditions are unlikely to model variations in environments that influence selection in wild populations. Thus, the study of “fitness” for survival and the genetics that influence this are best carried out in the field and in matching environments.</p><p>Therefore, we studied highland populations in their native environments, to learn how they cope with ambient hypoxia. The Andeans, African highlanders and Himalayans have adapted differently to their hostile environment.</p><p>Chronic mountain sickness (CMS), a loss of adaptation to altitude, is common in the Andes, occasionally found in the Himalayas; and absent from the East African altitude plateau.</p><p>We compared molecular signatures (distinct patterns of gene expression) of hypoxia-related genes, in white blood cells (WBC) from Andeans with (n = 10), without CMS (n = 10) and sea-level controls from Lima (n = 20) with those obtained from CMS (n = 8) and controls (n = 5) Ladakhi subjects from the Tibetan altitude plateau. We further analyzed the expression of a subset of these genes in Ethiopian highlanders (n = 8). In all subjects, we performed the studies at their native altitude and after they were rendered normoxic.</p><p>We identified a gene that predicted CMS in Andeans and Himalayans (PDP2). After achieving normoxia, WBC gene expression still distinguished Andean and Himalayan CMS subjects.</p><p>Remarkably, analysis of the small subset of genes (n = 8) studied in all 3 highland populations showed normoxia induced gene expression changes in Andeans, but not in Ethiopians nor Himalayan controls. This is consistent with physiologic studies in which Ethiopians and Himalayans show a lack of responsiveness to hypoxia of the cerebral circulation and of the hypoxic ventilatory drive, and with the absence of CMS on the East African altitude plateau.</p></div>", "links"=>[], "tags"=>["adaptation", "mal-adaptation", "ambient", "ethiopian", "himalayan", "patterns"], "article_id"=>150289, "categories"=>["Molecular Biology", "Physiology", "Medicine", "Evolutionary Biology"], "users"=>["Guoqiang Xing", "Clifford Qualls", "Luis Huicho", "Maria River-Ch", "Tsering Stobdan", "Marat Slessarev", "Eitan Prisman", "Soji Ito", "Hong Wu", "Angchuk Norboo", "Diskit Dolma", "Moses Kunzang", "Tsering Norboo", "Jorge L. Gamboa", "Victoria E. Claydon", "Joseph Fisher", "Guta Zenebe", "Amha Gebremedhin", "Roger Hainsworth", "Ajay Verma", "Otto Appenzeller"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002342", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Adaptation_and_Mal_Adaptation_to_Ambient_Hypoxia_Andean_Ethiopian_and_Himalayan_Patterns/150289", "title"=>"Adaptation and Mal-Adaptation to Ambient Hypoxia; Andean, Ethiopian and Himalayan Patterns", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-06-04 00:04:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/930467"], "description"=>"<p>To assess the impact of specific genes on chronic mountain sickness-score (CMS-sc), using a sliding scale (continuous), we show an “impact table” for the combined (CMS & Controls) Himalayan (Ladakh) groups at native altitude <b><u>(A).</u></b></p><p>In univariate linear regression model, <b>PDP2</b> is found to be the most significant predictor of CMS-sc (highlighted). Adjusting for PDP2 eliminates the impact of the other genes on the CMS-sc (columns, ADJ for PDP2). However, adjusting PDP2 for each of the remaining genes, assayed here, strengthens the impact of PDP2 (columns, Adj. PDP2). This supports the importance of <b>PDP2</b> in predicting CMS-sc in the Himalayas just as in the Andes (For glossary of terms, see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002342#pone-0002342-t002\" target=\"_blank\">table 2</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002342#pone.0002342.s001\" target=\"_blank\">Text S1</a>).</p>", "links"=>[], "tags"=>["predicting", "hypoxia-related", "genes", "cms", "altitude", "4450"], "article_id"=>600888, "categories"=>["Molecular Biology", "Physiology", "Medicine", "Evolutionary Biology"], "users"=>["Guoqiang Xing", "Clifford Qualls", "Luis Huicho", "Maria River-Ch", "Tsering Stobdan", "Marat Slessarev", "Eitan Prisman", "Soji Ito", "Hong Wu", "Angchuk Norboo", "Diskit Dolma", "Moses Kunzang", "Tsering Norboo", "Jorge L. Gamboa", "Victoria E. Claydon", "Joseph Fisher", "Guta Zenebe", "Amha Gebremedhin", "Roger Hainsworth", "Ajay Verma", "Otto Appenzeller"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002342.t004", "stats"=>{"downloads"=>3, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impact_table_to_show_the_predicting_power_of_specific_hypoxia_related_genes_on_CMS_CMS_score_8805_12_in_the_Himalayas_Korzok_village_altitude_4450_m_/600888", "title"=>"Impact table to show the predicting power of specific hypoxia-related genes on CMS (CMS-score≥12) in the Himalayas. (Korzok village altitude 4450 m.).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-06-04 00:14:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/930236"], "description"=>"<p>Values are reported either at high altitude (HIGH), or low altitude (LOW) in Peru and Ethiopia. The Himalayans were studied at the same altitude in ambient air (ambient) and after 1 hour of hyperoxia. <sup>§</sup> From reference <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002342#pone.0002342-Appenzeller1\" target=\"_blank\">[22]</a>.</p>†<p>P = 0.004. <sup>*</sup>P = 0.02. <sup>**</sup>P<0.01 compared to Ethiopians. …….. = no change; NA = not done.</p>", "links"=>[], "tags"=>["cardiovascular disorders", "molecular biology", "molecular biology/post-translational regulation of gene expression", "physiology/cardiovascular physiology and circulation", "evolutionary biology/human evolution"], "article_id"=>600666, "categories"=>["Molecular Biology", "Physiology", "Medicine", "Evolutionary Biology"], "users"=>["Guoqiang Xing", "Clifford Qualls", "Luis Huicho", "Maria River-Ch", "Tsering Stobdan", "Marat Slessarev", "Eitan Prisman", "Soji Ito", "Hong Wu", "Angchuk Norboo", "Diskit Dolma", "Moses Kunzang", "Tsering Norboo", "Jorge L. Gamboa", "Victoria E. Claydon", "Joseph Fisher", "Guta Zenebe", "Amha Gebremedhin", "Roger Hainsworth", "Ajay Verma", "Otto Appenzeller"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002342.t001", "stats"=>{"downloads"=>7, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demographics_of_our_study_populations_mean_177_SD_/600666", "title"=>"Demographics of our study populations. (mean±SD).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-06-04 00:11:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/930024"], "description"=>"<p>1-SaO2_ 2SD below normal for altitude; 2-Breathlesness, palpitations; 3-Sleep disturbances; 4-Cyanosis of lips, face or fingers; 5-dilated veins; 6-Paresthesias in fingers and/or toes; 7-Tinnitus; 8-Hb_2SD above normal for altitude; 9-Headache. *Denotes significant differences. In the Peruvian Andes the % of subjects having: sleep disturbances, paresthesias, tinnitus, high hemoglobin and headache were significantly higher*. Both populations were scored using an internationally accepted scoring system (≥12 = CMS)<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002342#pone.0002342-LeonVelarde1\" target=\"_blank\">[11]</a>.</p>", "links"=>[], "tags"=>["cms", "scores", "peruvian", "andes", "tibetan", "plateau"], "article_id"=>600443, "categories"=>["Molecular Biology", "Physiology", "Medicine", "Evolutionary Biology"], "users"=>["Guoqiang Xing", "Clifford Qualls", "Luis Huicho", "Maria River-Ch", "Tsering Stobdan", "Marat Slessarev", "Eitan Prisman", "Soji Ito", "Hong Wu", "Angchuk Norboo", "Diskit Dolma", "Moses Kunzang", "Tsering Norboo", "Jorge L. Gamboa", "Victoria E. Claydon", "Joseph Fisher", "Guta Zenebe", "Amha Gebremedhin", "Roger Hainsworth", "Ajay Verma", "Otto Appenzeller"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002342.g004", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Symptoms_Signs_Number_for_CMS_scores_in_the_Peruvian_Andes_4338_m_Peru_and_Tibetan_plateau_4450_m_Himalaya_/600443", "title"=>"Symptoms (Signs) Number for CMS scores in the Peruvian Andes (4338 m. Peru) and Tibetan plateau (4450 m. Himalaya):", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-06-04 00:07:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/930082"], "description"=>"<p>Comparisons at altitude (left) and in normoxia (right), same (control) subjects in each ethnic group. Note the lack of change in expression signatures with normoxia in the Ethiopians except for (PDP1, P<0.04). In Himalayans none of the gene expressions were changed by normoxia. No differences in molecular signatures between the Andean study groups (CMS and controls) except significant differences by location (normoxia in Lima). There were significant decreases in expression at altitude for most genes, except for HPH1, EPO and HPH2 in Andeans; VEGFC was not assayed in Andeans at low altitude. The genes were: #4-VEGFC; #8-PDK1; #10-EPOR; #11-PDP1; #14-PDK2; #17-HPH1; #18-EPO; #19-HPH2.</p>", "links"=>[], "tags"=>["signatures", "subset", "genes", "examined", "himalayans"], "article_id"=>600508, "categories"=>["Molecular Biology", "Physiology", "Medicine", "Evolutionary Biology"], "users"=>["Guoqiang Xing", "Clifford Qualls", "Luis Huicho", "Maria River-Ch", "Tsering Stobdan", "Marat Slessarev", "Eitan Prisman", "Soji Ito", "Hong Wu", "Angchuk Norboo", "Diskit Dolma", "Moses Kunzang", "Tsering Norboo", "Jorge L. Gamboa", "Victoria E. Claydon", "Joseph Fisher", "Guta Zenebe", "Amha Gebremedhin", "Roger Hainsworth", "Ajay Verma", "Otto Appenzeller"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002342.g005", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_signatures_of_a_subset_of_genes_examined_in_Ethiopians_Himalayans_and_Andeans_/600508", "title"=>"Expression signatures of a subset of genes examined in Ethiopians, Himalayans and Andeans.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-06-04 00:08:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/930359"], "description"=>"<p>To assess the impact of specific genes on chronic mountain sickness-score (CMS-sc), using a sliding scale (continuous), we constructed an “impact table” for the combined (CMS & Controls) Cerro de Pasco groups at altitude (A).</p><p>In univariate linear regression model, <b>PDP2</b> is found to be the most significant predictor of CMS-sc (highlighted). Adjusting for <b>PDP2</b> eliminates the impact of the other genes on the CMS-sc (columns, ADJ for PDP2). However, adjusting PDP2 for each of the remaining genes, assayed here, strengthens the impact of PDP2 (columns, Adj. PDP2).</p><p>This supports the importance of <b>PDP2</b> in predicting CMS-sc.</p><p><b>PDP2</b> is the phosphatase that de-phosphorylates the E1-alpha subunit of pyruvate dehydrogenase which promotes pyruvate entry into the Krebs cycle,</p><p>The <b>STB</b> is the standardized estimate for the parameter estimate of an explanatory variable in the logistic regression model and is computed by</p><p>multiplying the estimate by the sample standard deviation for the explanatory variable and dividing by π/√3 [Ref. SAS 9.1; On Line Help] (For glossary of terms see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002342#pone.0002342.s001\" target=\"_blank\">Text S1</a>).</p>", "links"=>[], "tags"=>["predicting", "hypoxia-related", "genes", "cms", "andean", "subjects", "cerro", "de", "altitude", "4338"], "article_id"=>600765, "categories"=>["Molecular Biology", "Physiology", "Medicine", "Evolutionary Biology"], "users"=>["Guoqiang Xing", "Clifford Qualls", "Luis Huicho", "Maria River-Ch", "Tsering Stobdan", "Marat Slessarev", "Eitan Prisman", "Soji Ito", "Hong Wu", "Angchuk Norboo", "Diskit Dolma", "Moses Kunzang", "Tsering Norboo", "Jorge L. Gamboa", "Victoria E. Claydon", "Joseph Fisher", "Guta Zenebe", "Amha Gebremedhin", "Roger Hainsworth", "Ajay Verma", "Otto Appenzeller"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002342.t002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impact_table_to_show_the_predicting_power_of_specific_hypoxia_related_genes_on_CMS_CMS_score_8805_12_in_our_Andean_subjects_in_Cerro_de_Pasco_Peru_altitude_4338_m_/600765", "title"=>"Impact table to show the predicting power of specific hypoxia-related genes on CMS (CMS-score≥12) in our Andean subjects in Cerro de Pasco, Peru, altitude 4338 m.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-06-04 00:12:45"}

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  • {"unique-ip"=>"21", "full-text"=>"21", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"21", "full-text"=>"20", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"16", "full-text"=>"22", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"29", "full-text"=>"33", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"19", "full-text"=>"17", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"10", "full-text"=>"15", "pdf"=>"8", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"25", "full-text"=>"26", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"16", "full-text"=>"17", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2019", "month"=>"12"}

Relative Metric

{"start_date"=>"2008-01-01T00:00:00Z", "end_date"=>"2008-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[324, 674, 863, 1015, 1146, 1259, 1360, 1452, 1540, 1621, 1704, 1776, 1843, 1905, 1968, 2029, 2097, 2162, 2233, 2289, 2352, 2412, 2476, 2538, 2601, 2655, 2714, 2777, 2841, 2894, 2946, 2998, 3047, 3103, 3151, 3201, 3258, 3317, 3369, 3424, 3471, 3521, 3583, 3625, 3687, 3743, 3788, 3838, 3896, 3953, 4015, 4075, 4148, 4201, 4275, 4347, 4420, 4486, 4535, 4592, 4660, 4731, 4792, 4845, 4901, 4971, 5027, 5089, 5148, 5200, 5261, 5318, 5374]}, {"subject_area"=>"/Earth sciences", "average_usage"=>[355, 650, 946, 1060, 1167, 1272, 1389, 1483, 1569, 1646, 1740, 1800, 1882, 1945, 2025, 2102, 2176, 2233, 2307, 2387, 2492, 2577, 2671, 2718, 2801, 2863, 2925, 2994, 3056, 3123, 3195, 3286, 3332, 3372, 3437, 3494, 3579, 3678, 3749, 3806, 3876, 3982, 4050, 4134, 4208, 4284, 4394, 4443, 4497, 4720, 4806, 4868, 4941, 5006, 5080, 5147, 5212, 5267, 5335, 5399, 5492, 5561, 5618, 5680, 5747, 5820, 5886, 5977, 6036, 6071, 6109, 6144, 6188, 6239]}, {"subject_area"=>"/Ecology and environmental sciences", "average_usage"=>[376, 699, 876, 1017, 1214, 1298, 1422, 1532, 1613, 1702, 1795, 1881, 1953, 2034, 2101, 2153, 2217, 2265, 2337, 2416, 2513, 2581, 2656, 2723, 2785, 2847, 2926, 2995, 3111, 3162, 3202, 3244, 3289, 3341, 3390, 3443, 3497, 3532, 3593, 3661, 3707, 3755, 3834, 3926, 3997, 4048, 4104, 4145, 4195, 4244, 4303, 4392, 4457, 4539, 4613, 4670, 4723, 4794, 4847, 4910, 4962, 5018, 5108, 5162, 5231, 5303, 5389, 5431, 5476, 5518, 5579, 5603, 5652, 5705]}, {"subject_area"=>"/Medicine and health sciences/Pathology and laboratory medicine", "average_usage"=>[306, 629, 807, 954, 1065, 1186, 1291, 1390, 1486, 1554, 1623, 1692, 1755, 1817, 1881, 1955, 2001, 2057, 2132, 2209, 2264, 2323, 2404, 2464, 2526, 2602, 2661, 2705, 2770, 2834, 2884, 2942, 2987, 3043, 3097, 3144, 3176, 3234, 3263, 3316, 3368, 3445, 3512, 3578, 3632, 3669, 3729, 3763, 3809, 3859, 3909, 3986, 4088, 4176, 4215, 4263, 4367, 4455, 4503, 4556, 4617, 4668, 4722, 4774, 4830, 4895, 4955, 5022, 5086, 5119, 5158, 5239, 5299]}, {"subject_area"=>"/Physical sciences", "average_usage"=>[316, 648, 828, 974, 1107, 1224, 1324, 1403, 1481, 1567, 1645, 1736, 1798, 1846, 1908, 1967, 2031, 2088, 2149, 2201, 2260, 2305, 2376, 2434, 2491, 2538, 2598, 2657, 2710, 2757, 2815, 2860, 2907, 2972, 3022, 3070, 3113, 3157, 3213, 3267, 3326, 3388, 3427, 3493, 3550, 3612, 3666, 3715, 3775, 3836, 3900, 3978, 4042, 4105, 4156, 4235, 4314, 4370, 4441, 4511, 4615, 4676, 4744, 4791, 4849, 4915, 4982, 5035, 5099, 5173, 5228, 5303, 5352]}]}

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