Genomic Insights into the Formation of Human Populations in East Asia

厦门大学人类学研究所、厦门大学生命科学学院细胞应激生物学国家重点实验室王传超教授课题组与哈佛医学院David Reich教授团队合作，联合全球43个单位的85位共同作者组成的国际合作团队通过古DNA精细解析东亚人群形成历史。研究人员利用古DNA数据检验了东亚地区农业和语言共扩散理论，综合考古学、语言学等证据，该研究系统性地重构了东亚人群的形成、迁徙和混合历史。这是目前国内开展的东亚地区最大规模的考古基因组学研究，此次所报道的东亚地区古人基因组样本量是以往国内研究机构所发表的样本量总和的两倍，改变了东亚地区尤其是中国境内考古基因组学研究长期滞后的局面。 该研究是由王传超教授团队与哈佛医学院（David Reich教授）、德国马普人类历史科学研究所（Johannes Krause教授）、复旦大学现代人类学教育部重点实验室（李辉教授和金力院士）、维也纳大学进化人类学系（Ron Pinhasi副教授）、南洋理工大学人文学院（Hui-Yuan Yeh助理教授）、俄罗斯远东联邦大学科学博物馆（Alexander N Popov研究员）、西安交通大学（张虎勤教授）、蒙古国国家博物馆研究中心、乌兰巴托国立大学考古系、华盛顿大学人类学系、台湾成功大学考古所、加州大学人类学系等全球43个单位的85位共同作者组成的国际合作团队联合完成的。厦门大学人类学研究所、厦门大学生命科学学院细胞应激生物学国家重点实验室为论文第一完成单位。厦门大学人类学研究所韦兰海副教授、胡荣助理教授、郭健新博士后、何光林博士后和杨晓敏硕士参与了研究工作。The deep population history of East Asia remains poorly understood due to a lack of ancient DNA data and sparse sampling of present-day people1,2. We report genome-wide data from 166 East Asians dating to 6000 BCE-1000 CE and 46 present-day groups. Hunter-gatherers from Japan, the Amur River Basin, and people of Neolithic and Iron Age Taiwan and the Tibetan plateau are linked by a deeply-splitting lineage likely reflecting a Late Pleistocene coastal migration. We follow Holocene expansions from four regions. First, hunter-gatherers of Mongolia and the Amur River Basin have ancestry shared by Mongolic and Tungusic language speakers but do not carry West Liao River farmer ancestry contradicting theories that their expansion spread these proto-languages. Second, Yellow River Basin farmers at ～3000 BCE likely spread Sino-Tibetan languages as their ancestry dispersed both to Tibet where it forms up ～84% to some groups and to the Central Plain where it contributed ～59-84% to Han Chinese. Third, people from Taiwan ～1300 BCE to 800 CE derived ～75% ancestry from a lineage also common in modern Austronesian, Tai-Kadai and Austroasiatic speakers likely deriving from Yangtze River Valley farmers; ancient Taiwan people also derived ～25% ancestry from a northern lineage related to but different from Yellow River farmers implying an additional north-to-south expansion. Fourth, Yamnaya Steppe pastoralist ancestry arrived in western Mongolia after ～3000 BCE but was displaced by previously established lineages even while it persisted in western China as expected if it spread the ancestor of Tocharian Indo-European languages. Two later gene flows affected western Mongolia: after ～2000 BCE migrants with Yamnaya and European farmer ancestry, and episodic impacts of later groups with ancestry from Turan.We thank David Anthony, Ofer Bar-Yosef, Katherine Brunson, Rowan Flad, Pavel Flegontov,Qiaomei Fu, Wolfgang Haak, Iosif Lazaridis, Mark Lipson, Iain Mathieson, Richard Meadow,Inigo Olalde, Nick Patterson, Pontus Skoglund, Dan Xu, and the four reviewers for valuable comments. We thank Naruya Saitou and the Asian DNA Repository Consortium for sharing genotype data from present-day Japanese groups. We thank Toyohiro Nishimoto and Takashi Fujisawa from the Rebun Town Board of Education for sharing the Funadomari Jomon samples, and Hideyo Tanaka and Watru Nagahara from the Archeological Center of Chiba City who are excavators of the Rokutsu Jomon site. The excavations at Boisman-2 site (Boisman culture), the Pospelovo-1 site (Yankovsky culture), and the Roshino-4 site (Heishui Mohe culture) were funded by the Far Eastern Federal University and the Institute of History,Archaeology and Ethnology Far Eastern Branch of the Russian Academy of Sciences; research on Pospelovo-1 is funded by RFBR project number 18-09-40101. C.C.W was funded by the Max Planck Society, the National Natural Science Foundation of China (NSFC 31801040), the Nanqiang Outstanding Young Talents Program of Xiamen University (X2123302), the Major project of National Social Science Foundation of China (20&ZD248), a European Research Council (ERC) grant to Dan Xu (ERC-2019-ADG-883700-TRAM) and Fundamental Research Funds for the Central Universities (ZK1144). O.B. and Y.B. were funded by Russian Scientific Foundation grant 17-14-01345. H.M. was supported by the grant JSPS 16H02527. M.R. and C.C.W received funding from the ERC under the European Union’s Horizon 2020 research and innovation program (grant No 646612) to M.R. The research of C.S. is supported 30 by the Calleva Foundation and the Human Origins Research Fund. H.L was funded NSFC (91731303, 31671297), B&R International Joint Laboratory of Eurasian Anthropology (18490750300). J.K. was funded by DFG grant KR 4015/1-1, the Baden Württemberg Foundation, and the Max Planck Institute. Accelerator Mass Spectrometry radiocarbon dating work was supported by the National Science Foundation (NSF) (BCS-1460369) to D.J.K. and B.J.C. D.R. was funded by NSF grant BCS-1032255, NIH (NIGMS) grant GM100233, the Paul M. Allen Frontiers Group, John Templeton Foundation grant 61220, a gift from Jean-Francois Clin, and the Howard Hughes Medical Institute. 该研究得到了国家自然科学基金“中国东南各族群的遗传混合”、国家社科基金重大项目“多学科视角下的南岛语族的起源和形成研究”、厦门大学南强青年拔尖人才支持计划A类、中央高校基本科研业务费等资助

Social and Pedagogical Rehabilitation of Female Students with Disabilities

A model of social and pedagogical rehabilitation of female students with disabilities in the educational space of higher education is suggested. Experimental data obtained in a long-term experiment on the first-year female student living in the Siberian region served as a ground for the creation of the model. Within a framework of the Health and Education program female students of different universities in Krasnoyarsk were examined in the VALEO interuniversity health and wellness center. Comparative analysis showed that the female students of the basic medical group have higher rates of physical development and morphofunctional parameters compared to their peers who have disabilities, and in particular, musculoskeletal disorders. The model helped to develop methodological and organizational bases for the complex solution of issues of social and pedagogical rehabilitation and providing targeted support and assistance at the individual level. Motivation of female students to improve health by means of physical culture and adaptive sports, active participation in various activities of the university (Club of the Funny and Inventive, Valeada, different intellectual competitions, judging competitions, etc.) contribute to their social status. The data based on the model of interaction of the interuniversity health and wellness center with chairs of physical culture and valeology, as well as social services of universities and medical personnel can generate a higher level of social and pedagogical rehabilitation of female students with disabilities in terms of an institution of higher education, which promotes the creation of a socially adapted educational environment. The effectiveness of this approach is justified by the example of one of the universities in the city.Предлагается модель социально-педагогической реабилитации студенток с ограниченными физическими возможностями в образовательном пространстве высшего учебного заведения. Основанием к созданию модели послужил экспериментальный материал, полученный в многолетнем эксперименте на студентках-первокурсницах, проживающих в Сибирском регионе. В рамках программы «Здоровье и образование» студентки разных вузов Красноярска проходили обследование в межвузовском оздоровительном центре VALEO. Сравнительный анализ показал, что студентки основной медицинской группы имеют более высокие показатели физического развития и морфофункциональных параметров по сравнению с их сверстницами, имеющими ограниченные физические возможности, и в частности, повреждение опорно- двигательного аппарата. С помощью модели созданы методологические и организационные основы для комплексного решения вопросов социально-педагогической реабилитации и оказания адресной поддержки и помощи на индивидуальном уровне. Мотивация студенток на укрепление здоровья средствами физической культуры и адаптивного спорта, активное участие в различных мероприятиях вуза (КВН, Валеада, различные интеллектуальные олимпиады, судейство соревнований и т.п) способствует повышению их социального статуса. Представленные материалы на основе модели взаимодействия межвузовского оздоровительного центра с кафедрами физической культуры и валеологии, а также социальными службами вузов и медицинским персоналом, позволяют формировать на более высоком уровне социально-педагогическую реабилитацию студенток с ограниченными возможностями в условиях высшего учебного заведения, что способствует созданию социально адаптированной образовательной среды. Эффективность данного подхода обоснована на примере одного из вузов города

Chronology of Prehistoric Cultural Complexes of Sakhalin Island (Russian Far East)

From the 18th International Radiocarbon Conference held in Wellington, New Zealand, September 1-5, 2003.A chronological framework for the prehistoric cultural complexes of Sakhalin Island is presented based on 160 radiocarbon dates from 74 sites. The earliest 14C-dated site, Ogonki 5, corresponds to the Upper Paleolithic, about 19,500-17,800 BP. According to the 14C data, since about 8800 BP, there is a continuous sequence of Neolithic, Early Iron Age, and Medieval complexes. The Neolithic existed during approximately 8800-2800 BP. Transitional Neolithic-Early Iron Age complexes are dated to about 2800-2300 BP. The Early Iron Age may be dated to about 2500-1300 BP. The Middle Ages period is dated to approximately 1300-300 BP (VII-XVII centuries AD).The Radiocarbon archives are made available by Radiocarbon and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform February 202

Social and Pedagogical Rehabilitation of Female Students with Disabilities

A model of social and pedagogical rehabilitation of female students with disabilities in the educational space of higher education is suggested. Experimental data obtained in a long-term experiment on the first-year female student living in the Siberian region served as a ground for the creation of the model. Within a framework of the Health and Education program female students of different universities in Krasnoyarsk were examined in the VALEO interuniversity health and wellness center. Comparative analysis showed that the female students of the basic medical group have higher rates of physical development and morphofunctional parameters compared to their peers who have disabilities, and in particular, musculoskeletal disorders. The model helped to develop methodological and organizational bases for the complex solution of issues of social and pedagogical rehabilitation and providing targeted support and assistance at the individual level. Motivation of female students to improve health by means of physical culture and adaptive sports, active participation in various activities of the university (Club of the Funny and Inventive, Valeada, different intellectual competitions, judging competitions, etc.) contribute to their social status. The data based on the model of interaction of the interuniversity health and wellness center with chairs of physical culture and valeology, as well as social services of universities and medical personnel can generate a higher level of social and pedagogical rehabilitation of female students with disabilities in terms of an institution of higher education, which promotes the creation of a socially adapted educational environment. The effectiveness of this approach is justified by the example of one of the universities in the city.Предлагается модель социально-педагогической реабилитации студенток с ограниченными физическими возможностями в образовательном пространстве высшего учебного заведения. Основанием к созданию модели послужил экспериментальный материал, полученный в многолетнем эксперименте на студентках-первокурсницах, проживающих в Сибирском регионе. В рамках программы «Здоровье и образование» студентки разных вузов Красноярска проходили обследование в межвузовском оздоровительном центре VALEO. Сравнительный анализ показал, что студентки основной медицинской группы имеют более высокие показатели физического развития и морфофункциональных параметров по сравнению с их сверстницами, имеющими ограниченные физические возможности, и в частности, повреждение опорно- двигательного аппарата. С помощью модели созданы методологические и организационные основы для комплексного решения вопросов социально-педагогической реабилитации и оказания адресной поддержки и помощи на индивидуальном уровне. Мотивация студенток на укрепление здоровья средствами физической культуры и адаптивного спорта, активное участие в различных мероприятиях вуза (КВН, Валеада, различные интеллектуальные олимпиады, судейство соревнований и т.п) способствует повышению их социального статуса. Представленные материалы на основе модели взаимодействия межвузовского оздоровительного центра с кафедрами физической культуры и валеологии, а также социальными службами вузов и медицинским персоналом, позволяют формировать на более высоком уровне социально-педагогическую реабилитацию студенток с ограниченными возможностями в условиях высшего учебного заведения, что способствует созданию социально адаптированной образовательной среды. Эффективность данного подхода обоснована на примере одного из вузов города

SYSTEMIC LUPUS ERYTHEMATOSUS: CLINICAL RECOMMENDATIONS. PART 1

The article presents current data on the etiology, pathogenesis, and epidemiology of systemic lupus erythematosus (SLE). The SLE diagnosis details are considered with a description of each examination technique. Moreover, an assessment of reliability level of both evidence and recommendations for each thesis-recommendation are discussed thoroughly. The aspects of differential diagnosis and criteria for the diagnostic quality of SLE are revealed

Updated carrier rates for c.35delG (GJB2) associated with hearing loss in Russia and common c.35delG haplotypes in Siberia

Abstract Background Mutations in GJB2 gene are a major causes of deafness and their spectrum and prevalence are specific for various populations. The well-known mutation c.35delG is more frequent in populations of Caucasian origin. Data on the c.35delG prevalence in Russia are mainly restricted to the European part of this country. We aimed to estimate the carrier frequency of c.35delG in Western Siberia and thereby update current data on the c.35delG prevalence in Russia. According to a generally accepted hypothesis, c.35delG originated from a common ancestor in the Middle East or the Mediterranean ~ 10,000–14,000 years ago and spread throughout Europe with Neolithic migrations. To test the c.35delG common origin hypothesis, we have reconstructed haplotypes bearing c.35delG and evaluated the approximate age of c.35delG in Siberia. Methods The carrier frequency of c.35delG was estimated in 122 unrelated hearing individuals living in Western Siberia. For reconstruction of haplotypes bearing c.35delG, polymorphic D13S141, D13S175, D13S1853 flanking the GJB2 gene, and intragenic rs3751385 were genotyped in deaf patients homozygous for c.35delG (n = 24) and in unrelated healthy individuals negative for c.35delG (n = 67) living in Siberia. Results We present updated carrier rates for c.35delG in Russia complemented by new data on c.35delG carrier frequency in Russians living in Western Siberia (4.1%). Two common D13S141-c.35delG-D13S175-D13S1853 haplotypes, 126-c.35delG-105-202 and 124-c.35delG-105-202, were reconstructed in the c.35delG homozygotes from Siberia. Moreover, identical allelic composition of the two most frequent c.35delG haplotypes restricted by D13S141 and D13S175 was established in geographically remote regions: Siberia and Volga-Ural region (Russia) and Belarus (Eastern Europe). Conclusions Distribution of the c.35delG carrier frequency in Russia is characterized by pronounced ethno-geographic specificity with a downward trend from west to east. Comparative analysis of the c.35delG haplotypes supports a common origin of c.35delG in some regions of Russia (Volga-Ural region and Siberia) and in Eastern Europe (Belarus). A rough estimation of the c.35delG age in Siberia (about 4800 to 8100 years ago) probably reflects the early formation stages of the modern European population (including the European part of the contemporary territory of Russia) since the settlement of Siberia by Russians started only at the end of sixteenth century

1-O-Alkylglycerol Ethers from the Marine Sponge Guitarra abbotti and Their Cytotoxic Activity

The cytotoxicity-bioassay-guided fractionation of the ethanol extract from the marine sponge Guitarra abbotti, whose 1-O-alkyl-sn-glycerol ethers (AGEs) have not been investigated so far, led to the isolation of a complex lipid fraction containing, along with previously known compounds, six new lipids of the AGE type. The composition of the AGE fraction as well as the structures of 6 new and 22 previously known compounds were established using 1H and 13C NMR, GC/MS, and chemical conversion methods. The new AGEs were identified as: 1-O-(Z-docos-15-enyl)-sn-glycerol (1), 1-O-(Z-docos-17-enyl)-sn-glycerol (2), 1-O-(Z-tricos-15-enyl)-sn-glycerol (3), 1-O-(Z-tricos-16-enyl)-sn-glycerol (4), 1-O-(Z-tricos-17-enyl)-sn-glycerol (5), and 1-O-(Z-tetracos-15-enyl)-sn-glycerol (6). The isolated AGEs show weak cytotoxic activity in THP-1, HL-60, HeLa, DLD-1, SNU C4, SK-MEL-28, and MDA-MB-231 human cancer cells. A further cytotoxicity analysis in JB6 P+ Cl41 cells bearing mutated MAP kinase genes revealed that ERK2 and JNK1 play a cytoprotective role in the cellular response to the AGE-induced cytotoxic effects

Anti-Cancer Potential of Transiently Transfected HER2-Specific Human Mixed CAR-T and NK Cell Populations in Experimental Models: Initial Studies on Fucosylated Chondroitin Sulfate Usage for Safer Treatment

Human epidermal growth factor receptor 2 (HER2) is overexpressed in numerous cancer cell types. Therapeutic antibodies and chimeric antigen receptors (CARs) against HER2 were developed to treat human tumors. The major limitation of anti-HER2 CAR-T lymphocyte therapy is attributable to the low HER2 expression in a wide range of normal tissues. Thus, side effects are caused by CAR lymphocyte “on-target off-tumor” reactions. We aimed to develop safer HER2-targeting CAR-based therapy. CAR constructs against HER2 tumor-associated antigen (TAA) for transient expression were delivered into target T and natural killer (NK) cells by an effective and safe non-viral transfection method via nucleofection, excluding the risk of mutations associated with viral transduction. Different in vitro end-point and real-time assays of the CAR lymphocyte antitumor cytotoxicity and in vivo human HER2-positive tumor xenograft mice model proved potent cytotoxic activity of the generated CAR-T-NK cells. Our data suggest transient expression of anti-HER2 CARs in plasmid vectors by human lymphocytes as a safer treatment for HER2-positive human cancers. We also conducted preliminary investigations to elucidate if fucosylated chondroitin sulfate may be used as a possible agent to decrease excessive cytokine production without negative impact on the CAR lymphocyte antitumor effect

Anti-Cancer Potential of Transiently Transfected HER2-Specific Human Mixed CAR-T and NK Cell Populations in Experimental Models: Initial Studies on Fucosylated Chondroitin Sulfate Usage for Safer Treatment

Human epidermal growth factor receptor 2 (HER2) is overexpressed in numerous cancer cell types. Therapeutic antibodies and chimeric antigen receptors (CARs) against HER2 were developed to treat human tumors. The major limitation of anti-HER2 CAR-T lymphocyte therapy is attributable to the low HER2 expression in a wide range of normal tissues. Thus, side effects are caused by CAR lymphocyte “on-target off-tumor” reactions. We aimed to develop safer HER2-targeting CAR-based therapy. CAR constructs against HER2 tumor-associated antigen (TAA) for transient expression were delivered into target T and natural killer (NK) cells by an effective and safe non-viral transfection method via nucleofection, excluding the risk of mutations associated with viral transduction. Different in vitro end-point and real-time assays of the CAR lymphocyte antitumor cytotoxicity and in vivo human HER2-positive tumor xenograft mice model proved potent cytotoxic activity of the generated CAR-T-NK cells. Our data suggest transient expression of anti-HER2 CARs in plasmid vectors by human lymphocytes as a safer treatment for HER2-positive human cancers. We also conducted preliminary investigations to elucidate if fucosylated chondroitin sulfate may be used as a possible agent to decrease excessive cytokine production without negative impact on the CAR lymphocyte antitumor effect