Combining Relative Chronology and AMS 14C Dating to Contextualize ‘Megasites’, Serial Migrations and Diachronic Expressions of Material Culture in the Western Tripolye Culture, Ukraine

Scholarship regarding the Eneolithic Cucuteni-Tripolye cultural complex of Romania, Moldova and Ukraine has recently focused on ‘megasites’ of the Western Tripolye culture (WTC) in Central Ukraine. However, in order to properly contextualize such unusual phenomena, we must explore the broader typo-chronology of the WTC, which is suggestive of a high degree of mobility and technological transfer between regions. We report 28 new AMS 14C dates from sites representing diagnostic types and propose a high-resolution chronological sequence for the WTC’s development. Our results support the relative chronology and offer an opportunity to propose a new chronological synthesis for the WTC

Quantitative Organization of GABAergic Synapses in the Molecular Layer of the Mouse Cerebellar Cortex

In the cerebellar cortex, interneurons of the molecular layer (stellate and basket cells) provide GABAergic input to Purkinje cells, as well as to each other and possibly to other interneurons. GABAergic inhibition in the molecular layer has mainly been investigated at the interneuron to Purkinje cell synapse. In this study, we used complementary subtractive strategies to quantitatively assess the ratio of GABAergic synapses on Purkinje cell dendrites versus those on interneurons. We generated a mouse model in which the GABAA receptor α1 subunit (GABAARα1) was selectively removed from Purkinje cells using the Cre/loxP system. Deletion of the α1 subunit resulted in a complete loss of GABAAR aggregates from Purkinje cells, allowing us to determine the density of GABAAR clusters in interneurons. In a complementary approach, we determined the density of GABA synapses impinging on Purkinje cells using α-dystroglycan as a specific marker of inhibitory postsynaptic sites. Combining these inverse approaches, we found that synapses received by interneurons represent approximately 40% of all GABAergic synapses in the molecular layer. Notably, this proportion was stable during postnatal development, indicating synchronized synaptogenesis. Based on the pure quantity of GABAergic synapses onto interneurons, we propose that mutual inhibition must play an important, yet largely neglected, computational role in the cerebellar cortex

Localization of metabotropic glutamate receptors in the outer plexiform layer of the goldfish retina

We studied the localization of metabotropic glutamate receptors (mGluRs) in the goldfish outer plexiform layer by light-and electron-microscopical immunohistochemistry. The mGluR1α antibody labeled putative ON-type bipolar cell dendrites and horizontal cell processes in both rod spherules and cone triads. Immunolabeling for mGluR2/3 was absent in the rod synaptic complex but was found at horizontal cell dendrites directly opposing the cone synaptic ribbon. The mGluR5 antibody labeled Müller cell processes wrapping rod terminals and horizontal cell somata. The mGluR7 antibody labeled mainly horizontal cell dendrites invaginating rods and cones and some putative bipolar cell dendrites in the cone synaptic complex. The finding of abundant expression of various mGluRs in bipolar and horizontal cell dendrites suggests multiple sites of glutamatergic modulation in the outer retina

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

A genetic history of the pre-contact Caribbean

Humans settled the Caribbean about 6,000 years ago, and ceramic use and intensified agriculture mark a shift from the Archaic to the Ceramic Age at around 2,500 years ago1,2,3. Here we report genome-wide data from 174 ancient individuals from The Bahamas, Haiti and the Dominican Republic (collectively, Hispaniola), Puerto Rico, Curaçao and Venezuela, which we co-analysed with 89 previously published ancient individuals. Stone-tool-using Caribbean people, who first entered the Caribbean during the Archaic Age, derive from a deeply divergent population that is closest to Central and northern South American individuals; contrary to previous work4, we find no support for ancestry contributed by a population related to North American individuals. Archaic-related lineages were >98% replaced by a genetically homogeneous ceramic-using population related to speakers of languages in the Arawak family from northeast South America; these people moved through the Lesser Antilles and into the Greater Antilles at least 1,700 years ago, introducing ancestry that is still present. Ancient Caribbean people avoided close kin unions despite limited mate pools that reflect small effective population sizes, which we estimate to be a minimum of 500–1,500 and a maximum of 1,530–8,150 individuals on the combined islands of Puerto Rico and Hispaniola in the dozens of generations before the individuals who we analysed lived. Census sizes are unlikely to be more than tenfold larger than effective population sizes, so previous pan-Caribbean estimates of hundreds of thousands of people are too large5,6. Confirming a small and interconnected Ceramic Age population7, we detect 19 pairs of cross-island cousins, close relatives buried around 75 km apart in Hispaniola and low genetic differentiation across islands. Genetic continuity across transitions in pottery styles reveals that cultural changes during the Ceramic Age were not driven by migration of genetically differentiated groups from the mainland, but instead reflected interactions within an interconnected Caribbean world1,8.This work was supported by a grant from the National Geographic Society to M. Pateman to facilitate analysis of skeletal material from The Bahamas and by a grant from the Italian ‘Ministry of Foreign Affairs and International Cooperation’ (Italian archaeological, anthropological and ethnological missions abroad, DGPSP Ufficio VI). D.R. was funded by NSF HOMINID grant BCS-1032255, NIH (NIGMS) grant GM100233, the Paul Allen Foundation, the John Templeton Foundation grant 61220 and the Howard Hughes Medical Institute.Peer reviewe

Interneuron- and GABAA receptor-specific inhibitory synaptic plasticity in cerebellar purkinje cells

Inhibitory synaptic plasticity is important for shaping both neuronal excitability and network activity. Here we investigate the input and GABA(A) receptor subunit specificity of inhibitory synaptic plasticity by studying cerebellar interneuron-Purkinje cell (PC) synapses. Depolarizing PCs initiated a long-lasting increase in GABA-mediated synaptic currents. By stimulating individual interneurons, this plasticity was observed at somatodendritic basket cell synapses, but not at distal dendritic stellate cell synapses. Basket cell synapses predominantly express β2-subunit-containing GABA(A) receptors; deletion of the β2-subunit ablates this plasticity, demonstrating its reliance on GABA(A) receptor subunit composition. The increase in synaptic currents is dependent upon an increase in newly synthesized cell surface synaptic GABA(A) receptors and is abolished by preventing CaMKII phosphorylation of GABA(A) receptors. Our results reveal a novel GABA(A) receptor subunit- and input-specific form of inhibitory synaptic plasticity that regulates the temporal firing pattern of the principal output cells of the cerebellum

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