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The timing and effect of the earliest human arrivals in North America 期刊论文
NATURE, 2020
作者:  Lorena Becerra-Valdivia;  Thomas Higham
收藏  |  浏览/下载:26/0  |  提交时间:2020/08/09

The peopling of the Americas marks a major expansion of humans across the planet. However, questions regarding the timing and mechanisms of this dispersal remain, and the previously accepted model (termed '  Clovis-first'  )-suggesting that the first inhabitants of the Americas were linked with the Clovis tradition, a complex marked by distinctive fluted lithic points(1)-has been effectively refuted. Here we analyse chronometric data from 42 North American and Beringian archaeological sites using a Bayesian age modelling approach, and use the resulting chronological framework to elucidate spatiotemporal patterns of human dispersal. We then integrate these patterns with the available genetic and climatic evidence. The data obtained show that humans were probably present before, during and immediately after the Last Glacial Maximum (about 26.5-19 thousand years ago)(2,3)but that more widespread occupation began during a period of abrupt warming, Greenland Interstadial 1 (about 14.7-12.9 thousand years beforead 2000)(4). We also identify the near-synchronous commencement of Beringian, Clovis and Western Stemmed cultural traditions, and an overlap of each with the last dates for the appearance of 18 now-extinct faunal genera. Our analysis suggests that the widespread expansion of humans through North America was a key factor in the extinction of large terrestrial mammals.


A Bayesian age model suggests that human dispersal to the Americas probably began before the Last Glacial Maximum, overlapping with the last dates of appearance for several faunal genera.


  
Extreme rainfall triggered the 2018 rift eruption at Kilauea Volcano 期刊论文
NATURE, 2020, 580 (7804) : 491-+
作者:  Cloutier, Richard;  Clement, Alice M.;  Lee, Michael S. Y.;  Noel, Roxanne;  Bechard, Isabelle;  Roy, Vincent;  Long, John A.
收藏  |  浏览/下载:33/0  |  提交时间:2020/05/13

The May 2018 rift intrusion and eruption of Kilauea Volcano, Hawai'  i, represented one of its most extraordinary eruptive sequences in at least 200 years, yet the trigger mechanism remains elusive(1). The event was preceded by several months of anomalously high precipitation. It has been proposed that rainfall can modulate shallow volcanic activity(2,3), but it remains unknown whether it can have impacts at the greater depths associated with magma transport. Here we show that immediately before and during the eruption, infiltration of rainfall into Kilauea Volcano'  s subsurface increased pore pressure at depths of 1 to 3 kilometres by 0.1 to 1 kilopascals, to its highest pressure in almost 50 years. We propose that weakening and mechanical failure of the edifice was driven by changes in pore pressure within the rift zone, prompting opportunistic dyke intrusion and ultimately facilitating the eruption. A precipitation-induced eruption trigger is consistent with the lack of precursory summit inflation, showing that this intrusion-unlike others-was not caused by the forceful intrusion of new magma into the rift zone. Moreover, statistical analysis of historic eruption occurrence suggests that rainfall patterns contribute substantially to the timing and frequency of Kilauea'  s eruptions and intrusions. Thus, volcanic activity can be modulated by extreme rainfall triggering edifice rock failure-a factor that should be considered when assessing volcanic hazards. Notably, the increasingly extreme weather patterns associated with ongoing anthropogenic climate change could increase the potential for rainfall-triggered volcanic phenomena worldwide.


Immediately before and during the eruption of Ki & x304  lauea Volcano in May 2018, anomalously high rainfall increased the pore pressure in the subsurface to its highest level in 50 years, causing weakening and mechanical failure of the edifice.


  
MAFG-driven astrocytes promote CNS inflammation 期刊论文
NATURE, 2020, 578 (7796) : 593-+
作者:  Clark, Peter U.;  He, Feng;  Golledge, Nicholas R.;  Mitrovica, Jerry X.;  Dutton, Andrea;  Hoffman, Jeremy S.;  Dendy, Sarah
收藏  |  浏览/下载:38/0  |  提交时间:2020/07/03

Multiple sclerosis is a chronic inflammatory disease of the CNS1. Astrocytes contribute to the pathogenesis of multiple sclerosis(2), but little is known about the heterogeneity of astrocytes and its regulation. Here we report the analysis of astrocytes in multiple sclerosis and its preclinical model experimental autoimmune encephalomyelitis (EAE) by single-cell RNA sequencing in combination with cell-specific Ribotag RNA profiling, assay for transposase-accessible chromatin with sequencing (ATAC-seq), chromatin immunoprecipitation with sequencing (ChIP-seq), genome-wide analysis of DNA methylation and in vivo CRISPR-Cas9-based genetic perturbations. We identified astrocytes in EAE and multiple sclerosis that were characterized by decreased expression of NRF2 and increased expression of MAFG, which cooperates with MAT2 alpha to promote DNA methylation and represses antioxidant and anti-inflammatory transcriptional programs. Granulocyte-macrophage colony-stimulating factor (GM-CSF) signalling in astrocytes drives the expression of MAFG and MAT2 alpha and pro-inflammatory transcriptional modules, contributing to CNS pathology in EAE and, potentially, multiple sclerosis. Our results identify candidate therapeutic targets in multiple sclerosis.


Single-cell RNA sequencing of cells from humans with multiple sclerosis and mice with a model of the disease identifies a population of disease-promoting astrocytes in which anti-oxidant and anti-inflammatory proteins are suppressed.


  
The strength and pattern of natural selection on gene expression in rice 期刊论文
NATURE, 2020, 578 (7796) : 572-+
作者:  Lipson, Mark;  Ribot, Isabelle;  Mallick, Swapan;  Rohland, Nadin;  Olalde, Inigo;  Adamski, Nicole;  Broomandkhoshbacht, Nasreen;  Lawson, Ann Marie;  Lopez, Saioa;  Oppenheimer, Jonas;  Stewardson, Kristin
收藏  |  浏览/下载:18/0  |  提交时间:2020/07/03

Levels of gene expression underpin organismal phenotypes(1,2), but the nature of selection that acts on gene expression and its role in adaptive evolution remain unknown(1,2). Here we assayed gene expression in rice (Oryza sativa)(3), and used phenotypic selection analysis to estimate the type and strength of selection on the levels of more than 15,000 transcripts(4,5). Variation in most transcripts appears (nearly) neutral or under very weak stabilizing selection in wet paddy conditions (with median standardized selection differentials near zero), but selection is stronger under drought conditions. Overall, more transcripts are conditionally neutral (2.83%) than are antagonistically pleiotropic(6) (0.04%), and transcripts that display lower levels of expression and stochastic noise(7-9) and higher levels of plasticity(9) are under stronger selection. Selection strength was further weakly negatively associated with levels of cis-regulation and network connectivity(9). Our multivariate analysis suggests that selection acts on the expression of photosynthesis genes(4,5), but that the efficacy of selection is genetically constrained under drought conditions(10). Drought selected for earlier flowering(11,12) and a higher expression of OsMADS18 (Os07g0605200), which encodes a MADS-box transcription factor and is a known regulator of early flowering(13)-marking this gene as a drought-escape gene(11,12). The ability to estimate selection strengths provides insights into how selection can shape molecular traits at the core of gene action.


Phenotypic selection analysis is used to estimate the type and strength of selection that acts on more than 15,000 transcripts in rice (Oryza sativa), which provides insight into the adaptive evolutionary role of selection on gene expression.


  
Structure of SAGA and mechanism of TBP deposition on gene promoters 期刊论文
NATURE, 2020, 577 (7792) : 711-+
作者:  Xue, Jenny Y.;  Zhao, Yulei;  Aronowitz, Jordan;  Mai, Trang T.;  Vides, Alberto;  Qeriqi, Besnik;  Kim, Dongsung;  Li, Chuanchuan;  de Stanchina, Elisa;  Mazutis, Linas;  Risso, Davide;  Lito, Piro
收藏  |  浏览/下载:33/0  |  提交时间:2020/07/03

SAGA (Spt-Ada-Gcn5-acetyltransferase) is a 19-subunit complex that stimulates transcription via two chromatin-modifying enzymatic modules and by delivering the TATA box binding protein (TBP) to nucleate the pre-initiation complex on DNA, a pivotal event in the expression of protein-encoding genes(1). Here we present the structure of yeast SAGA with bound TBP. The core of the complex is resolved at 3.5 angstrom resolution (0.143 Fourier shell correlation). The structure reveals the intricate network of interactions that coordinate the different functional domains of SAGA and resolves an octamer of histone-fold domains at the core of SAGA. This deformed octamer deviates considerably from the symmetrical analogue in the nucleosome and is precisely tuned to establish a peripheral site for TBP, where steric hindrance represses binding of spurious DNA. Complementary biochemical analysis points to a mechanism for TBP delivery and release from SAGA that requires transcription factor IIA and whose efficiency correlates with the affinity of DNA to TBP. We provide the foundations for understanding the specific delivery of TBP to gene promoters and the multiple roles of SAGA in regulating gene expression.


Structural studies on the yeast transcription coactivator complex SAGA (Spt-Ada-Gcn5-acetyltransferase) provide insights into the mechanism of initiation of regulated transcription by this multiprotein complex, which is conserved among eukaryotes.


  
B cells are associated with survival and immunotherapy response in sarcoma 期刊论文
NATURE, 2020, 577 (7791) : 556-+
作者:  Willis, J. P.;  Canning, R. E. A.;  Noordeh, E. S.;  Allen, S. W.;  King, A. L.;  Mantz, A.;  Morris, R. G.;  Stanford, S. A.;  Brammer, G.
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03

Soft-tissue sarcomas represent a heterogeneous group of cancer, with more than 50 histological subtypes(1,2). The clinical presentation of patients with different subtypes is often atypical, and responses to therapies such as immune checkpoint blockade vary widely(3,4). To explain this clinical variability, here we study gene expression profiles in 608 tumours across subtypes of soft-tissue sarcoma. We establish an immune-based classification on the basis of the composition of the tumour microenvironment and identify five distinct phenotypes: immune-low (A and B), immune-high (D and E), and highly vascularized (C) groups. In situ analysis of an independent validation cohort shows that class E was characterized by the presence of tertiary lymphoid structures that contain T cells and follicular dendritic cells and are particularly rich in B cells. B cells are the strongest prognostic factor even in the context of high or low CD8(+) T cells and cytotoxic contents. The class-E group demonstrated improved survival and a high response rate to PD1 blockade with pembrolizumab in a phase 2 clinical trial. Together, this work confirms the immune subtypes in patients with soft-tissue sarcoma, and unravels the potential of B-cell-rich tertiary lymphoid structures to guide clinical decision-making and treatments, which could have broader applications in other diseases.


Immune profiling of the tumour microenvironment of soft-tissue sarcoma identifies a group of patients with high levels of B-cell infiltration and tertiary lymphoid structures that have improved survival and a high response rate to immune checkpoint blockade therapy.


  
Size-Resolved Characterization of the Chromophores in Atmospheric Particulate Matter From a Typical Coal-Burning City in China 期刊论文
JOURNAL OF GEOPHYSICAL RESEARCH-ATMOSPHERES, 2019
作者:  Chen, Qingcai;  Mu, Zhen;  Song, Wenhuai;  Wang, Yuqin;  Yang, Zhaohong;  Zhang, Lixin;  Zhang, Yan-Lin
收藏  |  浏览/下载:8/0  |  提交时间:2019/11/27
atmospheric chromophores  excitation-emission matrix (EEM)  size-resolved characterizations  parallel factor analysis (PARAFAC)  
A novel global urban typology framework for sustainable mobility futures 期刊论文
ENVIRONMENTAL RESEARCH LETTERS, 2019, 14 (9)
作者:  Oke, Jimi B.;  Aboutaleb, Youssef M.;  Akkinepally, Arun;  Azevedo, Carlos Lima;  Han, Yafei;  Zegras, P. Christopher;  Ferreira, Joseph;  Ben-Akiva, Moshe E.
收藏  |  浏览/下载:5/0  |  提交时间:2019/11/27
urban typologies  sustainable mobility  cities  clustering  data mining  factor analysis  
A stochastic weather model for generating daily precipitation series at ungauged locations in the Catskill Mountain region of New York state 期刊论文
INTERNATIONAL JOURNAL OF CLIMATOLOGY, 2019
作者:  Yeo, Myeong-Ho;  Frei, Allan;  Gelda, Rakesh K.;  Owens, Emmet M.
收藏  |  浏览/下载:13/0  |  提交时间:2019/11/27
climate regionalization  estimation of daily precipitation  ordinal factor analysis  principal component analysis  ungauged precipitation  
Excessive electricity intensity of Vietnam: Evidence from a comparative study of Asia-Pacific countries 期刊论文
ENERGY POLICY, 2019, 130: 409-417
作者:  Hien, P. D.
收藏  |  浏览/下载:5/0  |  提交时间:2019/11/27
Electricity intensity  Vietnam  Asia-Pacific economies  Inverted-U model  Factor analysis  State-owned enterprises