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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:28/0  |  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.


  
Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis 期刊论文
NATURE, 2020, 577 (7789) : 260-+
作者:  Kakiuchi, Nobuyuki;  Yoshida, Kenichi;  Uchino, Motoi;  Kihara, Takako;  Akaki, Kotaro;  Inoue, Yoshikage;  Kawada, Kenji;  Nagayama, Satoshi;  Yokoyama, Akira;  Yamamoto, Shuji;  Matsuura, Minoru;  Horimatsu, Takahiro;  Hirano, Tomonori;  Goto, Norihiro;  Takeuchi, Yasuhide;  Ochi, Yotaro;  Shiozawa, Yusuke;  Kogure, Yasunori;  Watatani, Yosaku;  Fujii, Yoichi;  Kim, Soo Ki;  Kon, Ayana;  Kataoka, Keisuke;  Yoshizato, Tetsuichi;  Nakagawa, Masahiro M.;  Yoda, Akinori;  Nanya, Yasuhito;  Makishima, Hideki;  Shiraishi, Yuichi;  Chiba, Kenichi;  Tanaka, Hiroko;  Sanada, Masashi;  Sugihara, Eiji;  Sato, Taka-aki;  Maruyama, Takashi;  Miyoshi, Hiroyuki;  Taketo, Makoto Mark;  Oishi, Jun;  Inagaki, Ryosaku;  Ueda, Yutaka;  Okamoto, Shinya;  Okajima, Hideaki;  Sakai, Yoshiharu;  Sakurai, Takaki;  Haga, Hironori;  Hirota, Seiichi;  Ikeuchi, Hiroki;  Nakase, Hiroshi;  Marusawa, Hiroyuki;  Chiba, Tsutomu;  Takeuchi, Osamu;  Miyano, Satoru;  Seno, Hiroshi;  Ogawa, Seishi
收藏  |  浏览/下载:80/0  |  提交时间:2020/07/03

Chronic inflammation is accompanied by recurring cycles of tissue destruction and repair and is associated with an increased risk of cancer(1-3). However, how such cycles affect the clonal composition of tissues, particularly in terms of cancer development, remains unknown. Here we show that in patients with ulcerative colitis, the inflamed intestine undergoes widespread remodelling by pervasive clones, many of which are positively selected by acquiring mutations that commonly involve the NFKBIZ, TRAF3IP2, ZC3H12A, PIGR and HNRNPF genes and are implicated in the downregulation of IL-17 and other pro-inflammatory signals. Mutational profiles vary substantially between colitis-associated cancer and non-dysplastic tissues in ulcerative colitis, which indicates that there are distinct mechanisms of positive selection in both tissues. In particular, mutations in NFKBIZ are highly prevalent in the epithelium of patients with ulcerative colitis but rarely found in both sporadic and colitis-associated cancer, indicating that NFKBIZ-mutant cells are selected against during colorectal carcinogenesis. In further support of this negative selection, we found that tumour formation was significantly attenuated in Nfkbiz-mutant mice and cell competition was compromised by disruption of NFKBIZ in human colorectal cancer cells. Our results highlight common and discrete mechanisms of clonal selection in inflammatory tissues, which reveal unexpected cancer vulnerabilities that could potentially be exploited for therapeutics in colorectal cancer.


  
A sensory appendage protein protects malaria vectors from pyrethroids 期刊论文
NATURE, 2020, 577 (7790) : 376-+
作者:  Coyle, Diane
收藏  |  浏览/下载:38/0  |  提交时间:2020/07/03

Pyrethroid-impregnated bed nets have driven considerable reductions in malaria-associated morbidity and mortality in Africa since the beginning of the century(1). The intense selection pressure exerted by bed nets has precipitated widespread and escalating resistance to pyrethroids in African Anopheles populations, threatening to reverse the gains that been made by malaria control(2). Here we show that expression of a sensory appendage protein (SAP2), which is enriched in the legs, confers pyrethroid resistance to Anopheles gambiae. Expression of SAP2 is increased in insecticide-resistant populations and is further induced after the mosquito comes into contact with pyrethroids. SAP2 silencing fully restores mortality of the mosquitoes, whereas SAP2 overexpression results in increased resistance, probably owing to high-affinity binding of SAP2 to pyrethroid insecticides. Mining of genome sequence data reveals a selective sweep near the SAP2 locus in the mosquito populations of three West African countries (Cameroon, Guinea and Burkina Faso) with the observed increase in haplotype-associated single-nucleotide polymorphisms mirroring the increasing resistance of mosquitoes to pyrethroids reported in Burkina Faso. Our study identifies a previously undescribed mechanism of insecticide resistance that is likely to be highly relevant to malaria control efforts.


  
Population flow drives spatio-temporal distribution of COVID-19 in China 期刊论文
NATURE, 2020
作者:  Fernandez, Diego Carlos;  Komal, Ruchi;  Langel, Jennifer;  Ma, Jun;  Duy, Phan Q.;  Penzo, Mario A.;  Zhao, Haiqing;  Hattar, Samer
收藏  |  浏览/下载:70/0  |  提交时间:2020/07/03

Sudden, large-scale and diffuse human migration can amplify localized outbreaks of disease into widespread epidemics(1-4). Rapid and accurate tracking of aggregate population flows may therefore be epidemiologically informative. Here we use 11,478,484 counts of mobile phone data from individuals leaving or transiting through the prefecture of Wuhan between 1 January and 24 January 2020 as they moved to 296 prefectures throughout mainland China. First, we document the efficacy of quarantine in ceasing movement. Second, we show that the distribution of population outflow from Wuhan accurately predicts the relative frequency and geographical distribution of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) until 19 February 2020, across mainland China. Third, we develop a spatio-temporal '  risk source'  model that leverages population flow data (which operationalize the risk that emanates from epidemic epicentres) not only to forecast the distribution of confirmed cases, but also to identify regions that have a high risk of transmission at an early stage. Fourth, we use this risk source model to statistically derive the geographical spread of COVID-19 and the growth pattern based on the population outflow from Wuhan  the model yields a benchmark trend and an index for assessing the risk of community transmission of COVID-19 over time for different locations. This approach can be used by policy-makers in any nation with available data to make rapid and accurate risk assessments and to plan the allocation of limited resources ahead of ongoing outbreaks.


Modelling of population flows in China enables the forecasting of the distribution of confirmed cases of COVID-19 and the identification of areas at high risk of SARS-CoV-2 transmission at an early stage.


  
Dynamic RNA acetylation revealed by quantitative cross-evolutionary mapping 期刊论文
NATURE, 2020, 583 (7817) : 638-+
作者:  Lin, Yiheng;  Leibrandt, David R.;  Leibfriedz, Dietrich;  Chou, Chin-wen
收藏  |  浏览/下载:28/0  |  提交时间:2020/07/03

A method termed ac(4)C-seq is introduced for the transcriptome-wide mapping of the RNA modificationN(4)-acetylcytidine, revealing widespread temperature-dependent acetylation that facilitates thermoadaptation in hyperthermophilic archaea.


N-4-acetylcytidine (ac(4)C) is an ancient and highly conserved RNA modification that is present on tRNA and rRNA and has recently been investigated in eukaryotic mRNA(1-3). However, the distribution, dynamics and functions of cytidine acetylation have yet to be fully elucidated. Here we report ac(4)C-seq, a chemical genomic method for the transcriptome-wide quantitative mapping of ac(4)C at single-nucleotide resolution. In human and yeast mRNAs, ac(4)C sites are not detected but can be induced-at a conserved sequence motif-via the ectopic overexpression of eukaryotic acetyltransferase complexes. By contrast, cross-evolutionary profiling revealed unprecedented levels of ac(4)C across hundreds of residues in rRNA, tRNA, non-coding RNA and mRNA from hyperthermophilic archaea. (AcC)-C-4 is markedly induced in response to increases in temperature, and acetyltransferase-deficient archaeal strains exhibit temperature-dependent growth defects. Visualization of wild-type and acetyltransferase-deficient archaeal ribosomes by cryo-electron microscopy provided structural insights into the temperature-dependent distribution of ac(4)C and its potential thermoadaptive role. Our studies quantitatively define the ac(4)C landscape, providing a technical and conceptual foundation for elucidating the role of this modification in biology and disease(4-6).


  
Preparation of cyclohexene isotopologues and stereoisotopomers from benzene 期刊论文
NATURE, 2020, 581 (7808) : 288-+
作者:  Shimazaki, Yuya;  Schwartz, Ido;  Watanabe, Kenji;  Taniguchi, Takashi;  Kroner, Martin;  Imamoglu, Atac
收藏  |  浏览/下载:13/0  |  提交时间:2020/07/03

The hydrogen isotopes deuterium (D) and tritium (T) have become essential tools in chemistry, biology and medicine(1). Beyond their widespread use in spectroscopy, mass spectrometry and mechanistic and pharmacokinetic studies, there has been considerable interest in incorporating deuterium into drug molecules(1). Deutetrabenazine, a deuterated drug that is promising for the treatment of Huntington'  s disease(2), was recently approved by the United States'  Food and Drug Administration. The deuterium kinetic isotope effect, which compares the rate of a chemical reaction for a compound with that for its deuterated counterpart, can be substantial(1,3,4). The strategic replacement of hydrogen with deuterium can affect both the rate of metabolism and the distribution of metabolites for a compound(5), improving the efficacy and safety of a drug. The pharmacokinetics of a deuterated compound depends on the location(s) of deuterium. Although methods are available for deuterium incorporation at both early and late stages of the synthesis of a drug(6,7), these processes are often unselective and the stereoisotopic purity can be difficult to measure(7,8). Here we describe the preparation of stereoselectively deuterated building blocks for pharmaceutical research. As a proof of concept, we demonstrate a four-step conversion of benzene to cyclohexene with varying degrees of deuterium incorporation, via binding to a tungsten complex. Using different combinations of deuterated and proteated acid and hydride reagents, the deuterated positions on the cyclohexene ring can be controlled precisely. In total, 52 unique stereoisotopomers of cyclohexene are available, in the form of ten different isotopologues. This concept can be extended to prepare discrete stereoisotopomers of functionalized cyclohexenes. Such systematic methods for the preparation of pharmacologically active compounds as discrete stereoisotopomers could improve the pharmacological and toxicological properties of drugs and provide mechanistic information related to their distribution and metabolism in the body.


Cyclohexene isotopologues and stereoisotopomers with varying degrees of deuteration are formed by binding a tungsten complex to benzene, which facilitates the selective incorporation of deuterium into any position on the ring.


  
Massively parallel coherent laser ranging using a soliton microcomb 期刊论文
NATURE, 2020, 581 (7807) : 164-+
作者:  Casanova, Emmanuelle;  Knowles, Timothy D. J.;  Bayliss, Alex;  Dunne, Julie;  Baranski, Marek Z.;  Denaire, Anthony;  Lefranc, Philippe;  di Lernia, Savino;  Roffet-Salque, Melanie;  Smyth, Jessica;  Barclay, Alistair;  Gillard, Toby;  Classen, Erich;  Coles, Bryony;  Ilett, Michael;  Jeunesse, Christian;  Krueger, Marta;  Marciniak, Arkadiusz;  Minnitt, Steve;  Rotunno, Rocco;  van de Velde, Pieter;  van Wijk, Ivo;  Cotton, Jonathan;  Daykin, Andy;  Evershed, Richard P.
收藏  |  浏览/下载:46/0  |  提交时间:2020/07/03

Coherent ranging, also known as frequency-modulated continuous-wave (FMCW) laser-based light detection and ranging (lidar)(1) is used for long-range three-dimensional distance and velocimetry in autonomous driving(2,3). FMCW lidar maps distance to frequency(4,5) using frequency-chirped waveforms and simultaneously measures the Doppler shift of the reflected laser light, similar to sonar or radar(6,7) and coherent detection prevents interference from sunlight and other lidar systems. However, coherent ranging has a lower acquisition speed and requires precisely chirped(8) and highly coherent(5) laser sources, hindering widespread use of the lidar system and impeding parallelization, compared to modern time-of-flight ranging systems that use arrays of individual lasers. Here we demonstrate a massively parallel coherent lidar scheme using an ultra-low-loss photonic chip-based soliton microcomb(9). By fast chirping of the pump laser in the soliton existence range(10) of a microcomb with amplitudes of up to several gigahertz and a sweep rate of up to ten megahertz, a rapid frequency change occurs in the underlying carrier waveform of the soliton pulse stream, but the pulse-to-pulse repetition rate of the soliton pulse stream is retained. As a result, the chirp from a single narrow-linewidth pump laser is transferred to all spectral comb teeth of the soliton at once, thus enabling parallelism in the FMCW lidar. Using this approach we generate 30 distinct channels, demonstrating both parallel distance and velocity measurements at an equivalent rate of three megapixels per second, with the potential to improve sampling rates beyond 150 megapixels per second and to increase the image refresh rate of the FMCW lidar by up to two orders of magnitude without deterioration of eye safety. This approach, when combined with photonic phase arrays(11) based on nanophotonic gratings(12), provides a technological basis for compact, massively parallel and ultrahigh-frame-rate coherent lidar systems.


  
A calcineurin-Hoxb13 axis regulates growth mode of mammalian cardiomyocytes 期刊论文
NATURE, 2020, 582 (7811) : 271-+
作者:  Waszak, Sebastian M.;  Robinson, Giles W.;  Gudenas, Brian L.;  Smith, Kyle S.;  Forget, Antoine;  Kojic, Marija;  Garcia-Lopez, Jesus;  Hadley, Jennifer;  Hamilton, Kayla V.;  Indersie, Emilie;  Buchhalter, Ivo;  Kerssemakers, Jules;  Jaeger, Natalie;  Sharma, Tanvi;  Rausch, Tobias
收藏  |  浏览/下载:22/0  |  提交时间:2020/07/03

Hoxb13 acts as a cofactor of Meis1 in regulating cardiomyocyte maturation and cell cycle, and knockout of both proteins enables regeneration of postnatal cardiac tissue in a mouse model of heart injury.


A major factor in the progression to heart failure in humans is the inability of the adult heart to repair itself after injury. We recently demonstrated that the early postnatal mammalian heart is capable of regeneration following injury through proliferation of preexisting cardiomyocytes(1,2) and that Meis1, a three amino acid loop extension (TALE) family homeodomain transcription factor, translocates to cardiomyocyte nuclei shortly after birth and mediates postnatal cell cycle arrest(3). Here we report that Hoxb13 acts as a cofactor of Meis1 in postnatal cardiomyocytes. Cardiomyocyte-specific deletion of Hoxb13 can extend the postnatal window of cardiomyocyte proliferation and reactivate the cardiomyocyte cell cycle in the adult heart. Moreover, adult Meis1-Hoxb13 double-knockout hearts display widespread cardiomyocyte mitosis, sarcomere disassembly and improved left ventricular systolic function following myocardial infarction, as demonstrated by echocardiography and magnetic resonance imaging. Chromatin immunoprecipitation with sequencing demonstrates that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and cell cycle. Finally, we show that the calcium-activated protein phosphatase calcineurin dephosphorylates Hoxb13 at serine-204, resulting in its nuclear localization and cell cycle arrest. These results demonstrate that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and proliferation and provide mechanistic insights into the link between hyperplastic and hypertrophic growth of cardiomyocytes.


  
Intraplate volcanism originating from upwelling hydrous mantle transition zone 期刊论文
NATURE, 2020
作者:  Calabrese, Claudia;  Davidson, Natalie R.;  Demircioglu, Deniz;  Fonseca, Nuno A.;  He, Yao;  Kahles, Andre;  Kjong-Van Lehmann;  Liu, Fenglin;  Shiraishi, Yuichi;  Soulette, Cameron M.;  Urban, Lara;  Greger, Liliana;  Li, Siliang;  Liu, Dongbing;  Perry, Marc D.;  Xiang, Qian;  Zhang, Fan;  Zhang, Junjun;  Bailey, Peter;  Erkek, Serap;  Hoadley, Katherine A.;  Hou, Yong;  Huska, Matthew R.;  Kilpinen, Helena;  Korbel, Jan O.;  Marin, Maximillian G.;  Markowski, Julia;  Nandi, Tannistha;  Pan-Hammarstrom, Qiang;  Pedamallu, Chandra Sekhar;  Siebert, Reiner;  Stark, Stefan G.;  Su, Hong;  Tan, Patrick;  Waszak, Sebastian M.;  Yung, Christina;  Zhu, Shida;  Awadalla, Philip;  Creighton, Chad J.;  Meyerson, Matthew;  Ouellette, B. F. Francis;  Wu, Kui;  Yang, Huanming;  Brazma, Alvis;  Brooks, Angela N.;  Goke, Jonathan;  Raetsch, Gunnar;  Schwarz, Roland F.;  Stegle, Oliver;  Zhang, Zemin
收藏  |  浏览/下载:83/0  |  提交时间:2020/05/13

Most magmatism occurring on Earth is conventionally attributed to passive mantle upwelling at mid-ocean ridges, to slab devolatilization at subduction zones, or to mantle plumes. However, the widespread Cenozoic intraplate volcanism in northeast China(1-3) and the young petit-spot volcanoes(4-7) offshore of the Japan Trench cannot readily be associated with any of these mechanisms. In addition, the mantle beneath these types of volcanism is characterized by zones of anomalously low seismic velocity above and below the transition zone(8-12) (a mantle level located at depths between 410 and 660 kilometres). A comprehensive interpretation of these phenomena is lacking. Here we show that most (or possibly all) of the intraplate and petit-spot volcanism and low-velocity zones around the Japanese subduction zone can be explained by the Cenozoic interaction of the subducting Pacific slab with a hydrous mantle transition zone. Numerical modelling indicates that 0.2 to 0.3 weight per cent of water dissolved in mantle minerals that are driven out from the transition zone in response to subduction and retreat of a tectonic plate is sufficient to reproduce the observations. This suggests that a critical amount of water may have accumulated in the transition zone around this subduction zone, as well as in others of the Tethyan tectonic belt(13) that are characterized by intraplate or petit-spot volcanism and low-velocity zones in the underlying mantle.


The widespread intraplate volcanism in northeast China and the unusual '  petit-spot'  volcanoes offshore Japan could have resulted from the interaction of the subducting Pacific slab with a hydrous mantle transition zone.


  
Ancient West African foragers in the context of African population history 期刊论文
NATURE, 2020, 577 (7792) : 665-+
作者:  Grunwald, Hannah A.;  Gantz, Valentino M.;  Poplawski, Gunnar;  Xu, Xiang-Ru S.;  Bier, Ethan;  Cooper, Kimberly L.
收藏  |  浏览/下载:24/0  |  提交时间:2020/07/03

Genome-wide ancestry profiles of four individuals, dating to 8,000 and 3,000 years before present, from the archaeological site of Shum Laka (Cameroon) shed light on the deep population history of sub-Saharan Africa.


Our knowledge of ancient human population structure in sub-Saharan Africa, particularly prior to the advent of food production, remains limited. Here we report genome-wide DNA data from four children-two of whom were buried approximately 8,000 years ago and two 3,000 years ago-from Shum Laka (Cameroon), one of the earliest known archaeological sites within the probable homeland of the Bantu language group(1-11). One individual carried the deeply divergent Y chromosome haplogroup A00, which today is found almost exclusively in the same region(12,13). However, the genome-wide ancestry profiles of all four individuals are most similar to those of present-day hunter-gatherers from western Central Africa, which implies that populations in western Cameroon today-as well as speakers of Bantu languages from across the continent-are not descended substantially from the population represented by these four people. We infer an Africa-wide phylogeny that features widespread admixture and three prominent radiations, including one that gave rise to at least four major lineages deep in the history of modern humans.