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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：27/0  |  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.


  
Ice retreat in Wilkes Basin of East Antarctica during a warm interglacial 期刊论文
NATURE, 2020, 583 (7817) : 554-+
作者:  T. Blackburn;  G. H. Edwards;  S. Tulaczyk;  M. Scudder;  G. Piccione;  B. Hallet;  N. McLean;  J. C. Zachos;  B. Cheney;  J. T. Babbe
收藏  |  浏览/下载：21/0  |  提交时间：2020/08/09

Uranium isotopes in subglacial precipitates from the Wilkes Basin of the East Antarctic Ice Sheet reveal ice retreat during a warm Pleistocene interglacial period about 400,000 years ago.


Efforts to improve sea level forecasting on a warming planet have focused on determining the temperature, sea level and extent of polar ice sheets during Earth'  s past interglacial warm periods(1-3). About 400,000 years ago, during the interglacial period known as Marine Isotopic Stage 11 (MIS11), the global temperature was 1 to 2 degrees Celsius greater(2)and sea level was 6 to 13 metres higher(1,3). Sea level estimates in excess of about 10 metres, however, have been discounted because these require a contribution from the East Antarctic Ice Sheet(3), which has been argued to have remained stable for millions of years before and includes MIS11(4,5). Here we show how the evolution of(234)U enrichment within the subglacial waters of East Antarctica recorded the ice sheet'  s response to MIS11 warming. Within the Wilkes Basin, subglacial chemical precipitates of opal and calcite record accumulation of(234)U (the product of rock-water contact within an isolated subglacial reservoir) up to 20 times higher than that found in marine waters. The timescales of(234)U enrichment place the inception of this reservoir at MIS11. Informed by the(234)U cycling observed in the Laurentide Ice Sheet, where(234)U accumulated during periods of ice stability(6)and was flushed to global oceans in response to deglaciation(7), we interpret our East Antarctic dataset to represent ice loss within the Wilkes Basin at MIS11. The(234)U accumulation within the Wilkes Basin is also observed in the McMurdo Dry Valleys brines(8-10), indicating(11)that the brine originated beneath the adjacent East Antarctic Ice Sheet. The marine origin of brine salts(10)and bacteria(12)implies that MIS11 ice loss was coupled with marine flooding. Collectively, these data indicate that during one of the warmest Pleistocene interglacials, the ice sheet margin at the Wilkes Basin retreated to near the precipitate location, about 700 kilometres inland from the current position of the ice margin, which-assuming current ice volumes-would have contributed about 3 to 4 metres(13)to global sea levels.


  
A giant soft-shelled egg from the Late Cretaceous of Antarctica 期刊论文
NATURE, 2020
作者:  Lewnard, Joseph A.;  Lo, Nathan C.;  Arinaminpathy, Nimalan;  Frost, Isabel;  Laxminarayan, Ramanan
收藏  |  浏览/下载：16/0  |  提交时间：2020/06/22

Egg size and structure reflect important constraints on the reproductive and life-history characteristics of vertebrates(1). More than two-thirds of all extant amniotes lay eggs(2). During the Mesozoic era (around 250 million to 65 million years ago), body sizes reached extremes  nevertheless, the largest known egg belongs to the only recently extinct elephant bird(3), which was roughly 66 million years younger than the last nonavian dinosaurs and giant marine reptiles. Here we report a new type of egg discovered in nearshore marine deposits from the Late Cretaceous period (roughly 68 million years ago) of Antarctica. It exceeds all nonavian dinosaur eggs in volume and differs from them in structure. Although the elephant bird egg is slightly larger, its eggshell is roughly five times thicker and shows a substantial prismatic layer and complex pore structure(4). By contrast, the new fossil, visibly collapsed and folded, presents a thin eggshell with a layered structure that lacks a prismatic layer and distinct pores, and is similar to that of most extant lizards and snakes (Lepidosauria)(5). The identity of the animal that laid the egg is unknown, but these preserved morphologies are consistent with the skeletal remains of mosasaurs (large marine lepidosaurs) found nearby. They are not consistent with described morphologies of dinosaur eggs of a similar size class. Phylogenetic analyses of traits for 259 lepidosaur species plus outgroups suggest that the egg belonged to an individual that was at least 7 metres long, hypothesized to be a giant marine reptile, all clades of which have previously been proposed to show live birth(6). Such a large egg with a relatively thin eggshell may reflect derived constraints associated with body shape, reproductive investment linked with gigantism, and lepidosaurian viviparity, in which a '  vestigial'  egg is laid and hatches immediately(7).


A fossil egg unearthed from Cretaceous deposits in Antarctica is more than 20 cm long, exceeds all known nonavian eggs in volume, is soft-shelled, and was perhaps laid by a giant marine lizard such as a mosasaur.


  
International evaluation of an AI system for breast cancer screening 期刊论文
NATURE, 2020, 577 (7788) : 89-+
作者:  McKinney, Scott Mayer;  Sieniek, Marcin;  Godbole, Varun;  Godwin, Jonathan;  Antropova, Natasha;  Ashrafian, Hutan;  Back, Trevor;  Chesus, Mary;  Corrado, Greg C.;  Darzi, Ara;  Etemadi, Mozziyar;  Garcia-Vicente, Florencia;  Gilbert, Fiona J.;  Halling-Brown, Mark;  Hassabis, Demis;  Jansen, Sunny;  Karthikesalingam, Alan;  Kelly, Christopher J.;  King, Dominic;  Ledsam, Joseph R.;  Melnick, David;  Mostofi, Hormuz;  Peng, Lily;  Reicher, Joshua Jay;  Romera-Paredes, Bernardino;  Sidebottom, Richard;  Suleyman, Mustafa;  Tse, Daniel;  Young, Kenneth C.;  De Fauw, Jeffrey;  Shetty, Shravya
收藏  |  浏览/下载：15/0  |  提交时间：2020/07/03

Screening mammography aims to identify breast cancer at earlier stages of the disease, when treatment can be more successful(1). Despite the existence of screening programmes worldwide, the interpretation of mammograms is affected by high rates of false positives and false negatives(2). Here we present an artificial intelligence (AI) system that is capable of surpassing human experts in breast cancer prediction. To assess its performance in the clinical setting, we curated a large representative dataset from the UK and a large enriched dataset from the USA. We show an absolute reduction of 5.7% and 1.2% (USA and UK) in false positives and 9.4% and 2.7% in false negatives. We provide evidence of the ability of the system to generalize from the UK to the USA. In an independent study of six radiologists, the AI system outperformed all of the human readers: the area under the receiver operating characteristic curve (AUC-ROC) for the AI system was greater than the AUC-ROC for the average radiologist by an absolute margin of 11.5%. We ran a simulation in which the AI system participated in the double-reading process that is used in the UK, and found that the AI system maintained non-inferior performance and reduced the workload of the second reader by 88%. This robust assessment of the AI system paves the way for clinical trials to improve the accuracy and efficiency of breast cancer screening.


  
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：78/0  |  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.


  
Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer's disease 期刊论文
NATURE, 2020, 577 (7790) : 399-+
作者:  Gate, David;  Saligrama, Naresha;  Leventhal, Olivia;  Yang, Andrew C.;  Unger, Michael S.;  Middeldorp, Jinte;  Chen, Kelly;  Lehallier, Benoit;  Channappa, Divya;  De Los Santos, Mark B.;  McBride, Alisha;  Pluvinage, John;  Elahi, Fanny;  Tam, Grace Kyin-Ye;  Kim, Yongha;  Greicius, Michael;  Wagner, Anthony D.;  Aigner, Ludwig;  Galasko, Douglas R.;  Davis, Mark M.;  Wyss-Coray, Tony
收藏  |  浏览/下载：6/0  |  提交时间：2020/07/03

Alzheimer'  s disease is an incurable neurodegenerative disorder in which neuroinflammation has a critical function(1). However, little is known about the contribution of the adaptive immune response in Alzheimer'  s disease(2). Here, using integrated analyses of multiple cohorts, we identify peripheral and central adaptive immune changes in Alzheimer'  s disease. First, we performed mass cytometry of peripheral blood mononuclear cells and discovered an immune signature of Alzheimer'  s disease that consists of increased numbers of CD8(+) T effector memory CD45RA(+) (T-EMRA) cells. In a second cohort, we found that CD8(+) T-EMRA cells were negatively associated with cognition. Furthermore, single-cell RNA sequencing revealed that T cell receptor (TCR) signalling was enhanced in these cells. Notably, by using several strategies of single-cell TCR sequencing in a third cohort, we discovered clonally expanded CD8(+) T-EMRA cells in the cerebrospinal fluid of patients with Alzheimer'  s disease. Finally, we used machine learning, cloning and peptide screens to demonstrate the specificity of clonally expanded TCRs in the cerebrospinal fluid of patients with Alzheimer'  s disease to two separate Epstein-Barr virus antigens. These results reveal an adaptive immune response in the blood and cerebrospinal fluid in Alzheimer'  s disease and provide evidence of clonal, antigen-experienced T cells patrolling the intrathecal space of brains affected by age-related neurodegeneration.


  
Cortical pattern generation during dexterous movement is input-driven 期刊论文
NATURE, 2020, 577 (7790) : 386-+
作者:  Cyranoski, David
收藏  |  浏览/下载：9/0  |  提交时间：2020/07/03

The motor cortex controls skilled arm movement by sending temporal patterns of activity to lower motor centres(1). Local cortical dynamics are thought to shape these patterns throughout movement execution(2-4). External inputs have been implicated in setting the initial state of the motor cortex(5,6), but they may also have a pattern-generating role. Here we dissect the contribution of local dynamics and inputs to cortical pattern generation during a prehension task in mice. Perturbing cortex to an aberrant state prevented movement initiation, but after the perturbation was released, cortex either bypassed the normal initial state and immediately generated the pattern that controls reaching or failed to generate this pattern. The difference in these two outcomes was probably a result of external inputs. We directly investigated the role of inputs by inactivating the thalamus  this perturbed cortical activity and disrupted limb kinematics at any stage of the movement. Activation of thalamocortical axon terminals at different frequencies disrupted cortical activity and arm movement in a graded manner. Simultaneous recordings revealed that both thalamic activity and the current state of cortex predicted changes in cortical activity. Thus, the pattern generator for dexterous arm movement is distributed across multiple, strongly interacting brain regions.


  
Patterns and trends of Northern Hemisphere snow mass from 1980 to 2018 期刊论文
NATURE, 2020, 581 (7808) : 294-+
作者:  Ibrahim, Nizar;  Maganuco, Simone;  Dal Sasso, Cristiano;  Fabbri, Matteo;  Auditore, Marco;  Bindellini, Gabriele;  Martill, David M.;  Zouhri, Samir;  Mattarelli, Diego A.;  Unwin, David M.;  Wiemann, Jasmina;  Bonadonna, Davide;  Amane, Ayoub;  Jakubczak, Juliana;  Joger, Ulrich;  Lauder, George V.;  Pierce, Stephanie E.
收藏  |  浏览/下载：18/0  |  提交时间：2020/05/25

Warming surface temperatures have driven a substantial reduction in the extent and duration of Northern Hemisphere snow cover(1-3). These changes in snow cover affect Earth'  s climate system via the surface energy budget, and influence freshwater resources across a large proportion of the Northern Hemisphere(4-6). In contrast to snow extent, reliable quantitative knowledge on seasonal snow mass and its trend is lacking(7-9). Here we use the new GlobSnow 3.0 dataset to show that the 1980-2018 annual maximum snow mass in the Northern Hemisphere was, on average, 3,062 +/- 35 billion tonnes (gigatonnes). Our quantification is for March (the month that most closely corresponds to peak snow mass), covers non-alpine regions above 40 degrees N and, crucially, includes a bias correction based on in-field snow observations. We compare our GlobSnow 3.0 estimates with three independent estimates of snow mass, each with and without the bias correction. Across the four datasets, the bias correction decreased the range from 2,433-3,380 gigatonnes (mean 2,867) to 2,846-3,062 gigatonnes (mean 2,938)-a reduction in uncertainty from 33% to 7.4%. On the basis of our bias-corrected GlobSnow 3.0 estimates, we find different continental trends over the 39-year satellite record. For example, snow mass decreased by 46 gigatonnes per decade across North America but had a negligible trend across Eurasia  both continents exhibit high regional variability. Our results enable a better estimation of the role of seasonal snow mass in Earth'  s energy, water and carbon budgets.


Applying a bias correction to a state-of-the-art dataset covering non-alpine regions of the Northern Hemisphere and to three other datasets yields a more constrained quantification of snow mass in March from 1980 to 2018.


  
Millennial-scale hydroclimate control of tropical soil carbon storage 期刊论文
NATURE, 2020, 581 (7806) : 63-+
作者:  Lam, Tommy Tsan-Yuk;  Jia, Na;  Zhang, Ya-Wei;  Shum, Marcus Ho-Hin;  Jiang, Jia-Fu;  Zhu, Hua-Chen;  Tong, Yi-Gang;  Shi, Yong-Xia;  Ni, Xue-Bing;  Liao, Yun-Shi;  Li, Wen-Juan;  Jiang, Bao-Gui;  Wei, Wei;  Yuan, Ting-Ting;  Zheng, Kui;  Cui, Xiao-Ming;  Li, Jie;  Pei, Guang-Qian
收藏  |  浏览/下载：25/0  |  提交时间：2020/05/13

Over the past 18,000 years, the residence time and amount of soil carbon stored in the Ganges-Brahmaputra basin have been controlled by the intensity of Indian Summer Monsoon rainfall, with greater carbon destabilization during wetter, warmer conditions.


The storage of organic carbon in the terrestrial biosphere directly affects atmospheric concentrations of carbon dioxide over a wide range of timescales. Within the terrestrial biosphere, the magnitude of carbon storage can vary in response to environmental perturbations such as changing temperature or hydroclimate(1), potentially generating feedback on the atmospheric inventory of carbon dioxide. Although temperature controls the storage of soil organic carbon at mid and high latitudes(2,3), hydroclimate may be the dominant driver of soil carbon persistence in the tropics(4,5)  however, the sensitivity of tropical soil carbon turnover to large-scale hydroclimate variability remains poorly understood. Here we show that changes in Indian Summer Monsoon rainfall have controlled the residence time of soil carbon in the Ganges-Brahmaputra basin over the past 18,000 years. Comparison of radiocarbon ages of bulk organic carbon and terrestrial higher-plant biomarkers with co-located palaeohydrological records(6) reveals a negative relationship between monsoon rainfall and soil organic carbon stocks on a millennial timescale. Across the deglaciation period, a depletion of basin-wide soil carbon stocks was triggered by increasing rainfall and associated enhanced soil respiration rates. Our results suggest that future hydroclimate changes in tropical regions are likely to accelerate soil carbon destabilization, further increasing atmospheric carbon dioxide concentrations.


  
Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease 期刊论文
NATURE, 2020, 577 (7788) : 103-+
作者:  Lalaoui, Najoua;  Boyden, Steven E.;  Oda, Hirotsugu;  Wood, Geryl M.;  Stone, Deborah L.;  Chau, Diep;  Liu, Lin;  Stoffels, Monique;  Kratina, Tobias;  Lawlor, Kate E.;  Zaal, Kristien J. M.;  Hoffmann, Patrycja M.;  Etemadi, Nima;  Shield-Artin, Kristy;  Biben, Christine;  Tsai, Wanxia Li;  Blake, Mary D.;  Kuehn, Hye Sun;  Yang, Dan;  Anderton, Holly;  Silke, Natasha;  Wachsmuth, Laurens;  Zheng, Lixin;  Moura, Natalia Sampaio;  Beck, David B.;  Gutierrez-Cruz, Gustavo;  Ombrello, Amanda K.;  Pinto-Patarroyo, Gineth P.;  Kueh, Andrew J.;  Herold, Marco J.;  Hall, Cathrine;  Wang, Hongying;  Chae, Jae Jin;  Dmitrieva, Natalia I.;  McKenzie, Mark;  Light, Amanda;  Barham, Beverly K.;  Jones, Anne;  Romeo, Tina M.;  Zhou, Qing;  Aksentijevich, Ivona;  Mullikin, James C.;  Gross, Andrew J.;  Shum, Anthony K.;  Hawkins, Edwin D.;  Masters, Seth L.;  Lenardo, Michael J.;  Boehm, Manfred;  Rosenzweig, Sergio D.;  Pasparakis, Manolis;  Voss, Anne K.;  Gadina, Massimo;  Kastner, Daniel L.;  Silke, John
收藏  |  浏览/下载：24/0  |  提交时间：2020/07/03

RIPK1 is a key regulator of innate immune signalling pathways. To ensure an optimal inflammatory response, RIPK1 is regulated post-translationally by well-characterized ubiquitylation and phosphorylation events, as well as by caspase-8-mediated cleavage1-7. The physiological relevance of this cleavage event remains unclear, although it is thought to inhibit activation of RIPK3 and necroptosis8. Here we show that the heterozygous missense mutations D324N, D324H and D324Y prevent caspase cleavage of RIPK1 in humans and result in an early-onset periodic fever syndrome and severe intermittent lymphadenopathy-a condition we term '  cleavage-resistant RIPK1-induced autoinflammatory syndrome'  . To define the mechanism for this disease, we generated a cleavage-resistant Ripk1(D325A) mutant mouse strain. Whereas Ripk1(-/-) mice died postnatally from systemic inflammation, Ripk1(D325A/D325A) mice died during embryogenesis. Embryonic lethality was completely prevented by the combined loss of Casp8 and Ripk3, but not by loss of Ripk3 or Mlkl alone. Loss of RIPK1 kinase activity also prevented Ripk1(D325A/D325A) embryonic lethality, although the mice died before weaning from multi-organ inflammation in a RIPK3-dependent manner. Consistently, Ripk1(D325A/D325A) and Ripk1(D325A/+) cells were hypersensitive to RIPK3-dependent TNF-induced apoptosis and necroptosis. Heterozygous Ripk1(D325A/+) mice were viable and grossly normal, but were hyper-responsive to inflammatory stimuli in vivo. Our results demonstrate the importance of caspase-mediated RIPK1 cleavage during embryonic development and show that caspase cleavage of RIPK1 not only inhibits necroptosis but also maintains inflammatory homeostasis throughout life.