GSTDTAP

浏览/检索结果: 共60条,第1-10条 帮助

限定条件                        
已选(0)清除 条数/页:   排序方式:
HUGE COHORT STUDIES PIVOT TO INVESTIGATE THE CORONAVIRUS 期刊论文
NATURE, 2020, 582 (7812) : 326-326
作者:  Norell, Mark A.;  Wiemann, Jasmina;  Fabbri, Matteo;  Yu, Congyu;  Marsicano, Claudia A.;  Moore-Nall, Anita;  Varricchio, David J.;  Pol, Diego;  Zelenitsky, Darla K.
收藏  |  浏览/下载:13/0  |  提交时间:2020/07/03
Australian junior scientists report damaging lack of support at work 期刊论文
NATURE, 2020, 579 (7799) : 457-458
作者:  Aveline, David C.;  Williams, Jason R.;  Elliott, Ethan R.;  Dutenhoffer, Chelsea;  Kellogg, James R.;  Kohel, James M.;  Lay, Norman E.;  Oudrhiri, Kamal;  Shotwell, Robert F.;  Yu, Nan;  Thompson, Robert J.
收藏  |  浏览/下载:7/0  |  提交时间:2020/07/03
Molecular architecture of lineage allocation and tissue organization in early mouse embryo (vol 572, 528, 2019) 期刊论文
NATURE, 2020, 577 (7791) : E6-E6
作者:  Peng, Guangdun;  Suo, Shengbao;  Cui, Guizhong;  Yu, Fang;  Wang, Ran;  Chen, Jun;  Chen, Shirui;  Liu, Zhiwen;  Chen, Guoyu;  Qian, Yun;  Tam, Patrick P. L.;  Han, Jing-Dong J.;  Jing, Naihe
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03
A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1 期刊论文
NATURE, 2020, 577 (7788) : 109-+
作者:  Tao, Panfeng;  Sun, Jinqiao;  Wu, Zheming;  Wang, Shihao;  Wang, Jun;  Li, Wanjin;  Pan, Heling;  Bai, Renkui;  Zhang, Jiahui;  Wang, Ying;  Lee, Pui Y.;  Ying, Wenjing;  Zhou, Qinhua;  Hou, Jia;  Wang, Wenjie;  Sun, Bijun;  Yang, Mi;  Liu, Danru;  Fang, Ran;  Han, Huan;  Yang, Zhaohui;  Huang, Xin;  Li, Haibo;  Deuitch, Natalie;  Zhang, Yuan;  Dissanayake, Dilan;  Haude, Katrina;  McWalter, Kirsty;  Roadhouse, Chelsea;  MacKenzie, Jennifer J.;  Laxer, Ronald M.;  Aksentijevich, Ivona;  Yu, Xiaomin;  Wang, Xiaochuan;  Yuan, Junying;  Zhou, Qing
收藏  |  浏览/下载:26/0  |  提交时间:2020/07/03

Activation of RIPK1 controls TNF-mediated apoptosis, necroptosis and inflammatory pathways(1). Cleavage of human and mouse RIPK1 after residues D324 and D325, respectively, by caspase-8 separates the RIPK1 kinase domain from the intermediate and death domains. The D325A mutation in mouse RIPK1 leads to embryonic lethality during mouse development(2,3). However, the functional importance of blocking caspase-8-mediated cleavage of RIPK1 on RIPK1 activation in humans is unknown. Here we identify two families with variants in RIPK1 (D324V and D324H) that lead to distinct symptoms of recurrent fevers and lymphadenopathy in an autosomaldominant manner. Impaired cleavage of RIPK1 D324 variants by caspase-8 sensitized patients'  peripheral blood mononuclear cells to RIPK1 activation, apoptosis and necroptosis induced by TNF. The patients showed strong RIPK1-dependent activation of inflammatory signalling pathways and overproduction of inflammatory cytokines and chemokines compared with unaffected controls. Furthermore, we show that expression of the RIPK1 mutants D325V or D325H in mouse embryonic fibroblasts confers not only increased sensitivity to RIPK1 activation-mediated apoptosis and necroptosis, but also induction of pro-inflammatory cytokines such as IL-6 and TNF. By contrast, patient-derived fibroblasts showed reduced expression of RIPK1 and downregulated production of reactive oxygen species, resulting in resistance to necroptosis and ferroptosis. Together, these data suggest that human non-cleavable RIPK1 variants promote activation of RIPK1, and lead to an autoinflammatory disease characterized by hypersensitivity to apoptosis and necroptosis and increased inflammatory response in peripheral blood mononuclear cells, as well as a compensatory mechanism to protect against several pro-death stimuli in fibroblasts.


  
Monumental architecture at Aguada Fenix and the rise of Maya civilization 期刊论文
NATURE, 2020
作者:  Bedding, Timothy R.;  Murphy, Simon J.;  Hey, Daniel R.;  Huber, Daniel;  Li, Tanda;  Smalley, Barry;  Stello, Dennis;  White, Timothy R.;  Ball, Warrick H.;  Chaplin, William J.;  Colman, Isabel L.;  Fuller, Jim;  Gaidos, Eric;  Harbeck, Daniel R.;  Hermes, J. J.;  Holdsworth, Daniel L.;  Li, Gang;  Li, Yaguang;  Mann, Andrew W.;  Reese, Daniel R.;  Sekaran, Sanjay;  Yu, Jie;  Antoci, Victoria;  Bergmann, Christoph;  Brown, Timothy M.;  Howard, Andrew W.;  Ireland, Michael J.;  Isaacson, Howard;  Jenkins, Jon M.;  Kjeldsen, Hans;  McCully, Curtis;  Rabus, Markus;  Rains, Adam D.;  Ricker, George R.;  Tinney, Christopher G.;  Vanderspek, Roland K.
收藏  |  浏览/下载:30/0  |  提交时间:2020/07/03

Archaeologists have traditionally thought that the development of Maya civilization was gradual, assuming that small villages began to emerge during the Middle Preclassic period (1000-350 bc  dates are calibrated throughout) along with the use of ceramics and the adoption of sedentism(1). Recent finds of early ceremonial complexes are beginning to challenge this model. Here we describe an airborne lidar survey and excavations of the previously unknown site of Aguada Fenix (Tabasco, Mexico) with an artificial plateau, which measures 1,400 m in length and 10 to 15 m in height and has 9 causeways radiating out from it. We dated this construction to between 1000 and 800 bc using a Bayesian analysis of radiocarbon dates. To our knowledge, this is the oldest monumental construction ever found in the Maya area and the largest in the entire pre-Hispanic history of the region. Although the site exhibits some similarities to the earlier Olmec centre of San Lorenzo, the community of Aguada Fenix probably did not have marked social inequality comparable to that of San Lorenzo. Aguada Fenix and other ceremonial complexes of the same period suggest the importance of communal work in the initial development of Maya civilization.


Lidar survey of the Maya lowlands uncovers the monumental site of Aguada Fenix, which dates to around 1000-800 bc and points to the role of communal construction in the development of Maya civilization.


  
APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline 期刊论文
NATURE, 2020, 581 (7806) : 70-+
作者:  Doherty, Tiarnan A. S.;  Winchester, Andrew J.;  Macpherson, Stuart;  Johnstone, Duncan N.;  Pareek, Vivek;  Tennyson, Elizabeth M.;  Kosar, Sofiia;  Kosasih, Felix U.;  Anaya, Miguel;  Abdi-Jalebi, Mojtaba;  Andaji-Garmaroudi, Zahra;  Wong, E. Laine;  Madeo, Julien;  Chiang, Yu-Hsien;  Park, Ji-Sang;  Jung, Young-Kwang;  Petoukhoff, Christopher E.;  Divitini, Giorgio;  Man, Michael K. L.;  Ducati, Caterina;  Walsh, Aron;  Midgley, Paul A.;  Dani, Keshav M.;  Stranks, Samuel D.
收藏  |  浏览/下载:25/0  |  提交时间:2020/07/03

Breakdown of the blood-brain barrier in individuals carrying the epsilon 4 allele of the APOE gene, but not the epsilon 3 allele, increases with and predicts cognitive impairment and is independent of amyloid beta or tau pathology.


Vascular contributions to dementia and Alzheimer'  s disease are increasingly recognized(1-6). Recent studies have suggested that breakdown of the blood-brain barrier (BBB) is an early biomarker of human cognitive dysfunction(7), including the early clinical stages of Alzheimer'  s disease(5,8-10). The E4 variant of apolipoprotein E (APOE4), the main susceptibility gene for Alzheimer'  s disease(11-14), leads to accelerated breakdown of the BBB and degeneration of brain capillary pericytes(15-19), which maintain BBB integrity(20-22). It is unclear, however, whether the cerebrovascular effects of APOE4 contribute to cognitive impairment. Here we show that individuals bearing APOE4 (with the epsilon 3/epsilon 4 or epsilon 4/epsilon 4 alleles) are distinguished from those without APOE4 (epsilon 3/epsilon 3) by breakdown of the BBB in the hippocampus and medial temporal lobe. This finding is apparent in cognitively unimpaired APOE4 carriers and more severe in those with cognitive impairment, but is not related to amyloid-beta or tau pathology measured in cerebrospinal fluid or by positron emission tomography(23). High baseline levels of the BBB pericyte injury biomarker soluble PDGFR beta(7,8) in the cerebrospinal fluid predicted future cognitive decline in APOE4 carriers but not in non-carriers, even after controlling for amyloid-beta and tau status, and were correlated with increased activity of the BBB-degrading cyclophilin A-matrix metalloproteinase-9 pathway(19) in cerebrospinal fluid. Our findings suggest that breakdown of the BBB contributes to APOE4-associated cognitive decline independently of Alzheimer'  s disease pathology, and might be a therapeutic target in APOE4 carriers.


  
The dental proteome of Homo antecessor 期刊论文
NATURE, 2020, 580 (7802) : 235-+
作者:  Abram, Nerilie J.;  Wright, Nicky M.;  Ellis, Bethany;  Dixon, Bronwyn C.;  Wurtzel, Jennifer B.;  England, Matthew H.;  Ummenhofer, Caroline C.;  Philibosian, Belle;  Cahyarini, Sri Yudawati;  Yu, Tsai-Luen;  Shen, Chuan-Chou;  Cheng, Hai;  Edwards, R. Lawrence;  Heslop, David
收藏  |  浏览/下载:29/0  |  提交时间:2020/07/03

Analyses of the proteomes of dental enamel from Homo antecessor and Homo erectus demonstrate that the Early Pleistocene H. antecessor is a close sister lineage of later Homo sapiens, Neanderthal and Denisovan populations in Eurasia.


The phylogenetic relationships between hominins of the Early Pleistocene epoch in Eurasia, such as Homo antecessor, and hominins that appear later in the fossil record during the Middle Pleistocene epoch, such as Homo sapiens, are highly debated(1-5). For the oldest remains, the molecular study of these relationships is hindered by the degradation of ancient DNA. However, recent research has demonstrated that the analysis of ancient proteins can address this challenge(6-8). Here we present the dental enamel proteomes of H. antecessor from Atapuerca (Spain)(9,10) and Homo erectus from Dmanisi (Georgia)(1), two key fossil assemblages that have a central role in models of Pleistocene hominin morphology, dispersal and divergence. We provide evidence that H. antecessor is a close sister lineage to subsequent Middle and Late Pleistocene hominins, including modern humans, Neanderthals and Denisovans. This placement implies that the modern-like face of H. antecessor-that is, similar to that of modern humans-may have a considerably deep ancestry in the genus Homo, and that the cranial morphology of Neanderthals represents a derived form. By recovering AMELY-specific peptide sequences, we also conclude that the H. antecessor molar fragment from Atapuerca that we analysed belonged to a male individual. Finally, these H. antecessor and H. erectus fossils preserve evidence of enamel proteome phosphorylation and proteolytic digestion that occurred in vivo during tooth formation. Our results provide important insights into the evolutionary relationships between H. antecessor and other hominin groups, and pave the way for future studies using enamel proteomes to investigate hominin biology across the existence of the genus Homo.


  
Listeria monocytogenes impairs SUMOylation for efficient infection (vol 464, pg 1192, 2010) 期刊论文
NATURE, 2020, 580 (7805) : E20-E20
作者:  Abram, Nerilie J.;  Wright, Nicky M.;  Ellis, Bethany;  Dixon, Bronwyn C.;  Wurtzel, Jennifer B.;  England, Matthew H.;  Ummenhofer, Caroline C.;  Philibosian, Belle;  Cahyarini, Sri Yudawati;  Yu, Tsai-Luen;  Shen, Chuan-Chou;  Cheng, Hai;  Edwards, R. Lawrence;  Heslop, David
收藏  |  浏览/下载:9/0  |  提交时间:2020/07/03

An amendment to this paper has been published and can be accessed via a link at the top of the paper.


  
Live-animal imaging of native haematopoietic stem and progenitor cells 期刊论文
NATURE, 2020, 578 (7794) : 278-+
作者:  Gerstung, Moritz;  Jolly, Clemency;  Leshchiner, Ignaty;  Dentro, Stefan C.;  Gonzalez, Santiago;  Rosebrock, Daniel;  Mitchell, Thomas J.;  Rubanova, Yulia;  Anur, Pavana;  Yu, Kaixian;  Tarabichi, Maxime;  Deshwar, Amit;  Wintersinger, Jeff;  Kleinheinz, Kortine;  Vazquez-Garcia, Ignacio;  Haase, Kerstin;  Jerman, Lara;  Sengupta, Subhajit;  Macintyre, Geoff;  Malikic, Salem;  Donmez, Nilgun;  Livitz, Dimitri G.;  Cmero, Marek;  Demeulemeester, Jonas;  Schumacher, Steven;  Fan, Yu;  Yao, Xiaotong;  Lee, Juhee;  Schlesner, Matthias;  Boutros, Paul C.;  Bowtell, David D.;  Zhu, Hongtu;  Getz, Gad;  Imielinski, Marcin;  Beroukhim, Rameen;  Sahinalp, S. Cenk;  Ji, Yuan;  Peifer, Martin;  Markowetz, Florian;  Mustonen, Ville;  Yuan, Ke;  Wang, Wenyi;  Morris, Quaid D.;  Spellman, Paul T.;  Wedge, David C.;  Van Loo, Peter;  Deshwar, Amit G.;  Adams, David J.;  Campbell, Peter J.;  Cao, Shaolong;  Christie, Elizabeth L.;  Cun, Yupeng;  Dawson, Kevin J.;  Drews, Ruben M.;  Eils, Roland;  Fittall, Matthew;  Garsed, Dale W.;  Ha, Gavin;  Lee-Six, Henry;  Martincorena, Inigo;  Oesper, Layla;  Peto, Myron;  Raphael, Benjamin J.;  Salcedo, Adriana;  Shi, Ruian;  Shin, Seung Jun;  Spiro, Oliver;  Stein, Lincoln D.;  Vembu, Shankar;  Wheeler, David A.;  Yang, Tsun-Po
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03

The biology of haematopoietic stem cells (HSCs) has predominantly been studied under transplantation conditions(1,2). It has been particularly challenging to study dynamic HSC behaviour, given that the visualization of HSCs in the native niche in live animals has not, to our knowledge, been achieved. Here we describe a dual genetic strategy in mice that restricts reporter labelling to a subset of the most quiescent long-term HSCs (LT-HSCs) and that is compatible with current intravital imaging approaches in the calvarial bone marrow(3-5). We show that this subset of LT-HSCs resides close to both sinusoidal blood vessels and the endosteal surface. By contrast, multipotent progenitor cells (MPPs) show greater variation in distance from the endosteum and are more likely to be associated with transition zone vessels. LT-HSCs are not found in bone marrow niches with the deepest hypoxia and instead are found in hypoxic environments similar to those of MPPs. In vivo time-lapse imaging revealed that LT-HSCs at steady-state show limited motility. Activated LT-HSCs show heterogeneous responses, with some cells becoming highly motile and a fraction of HSCs expanding clonally within spatially restricted domains. These domains have defined characteristics, as HSC expansion is found almost exclusively in a subset of bone marrow cavities with bone-remodelling activity. By contrast, cavities with low bone-resorbing activity do not harbour expanding HSCs. These findings point to previously unknown heterogeneity within the bone marrow microenvironment, imposed by the stages of bone turnover. Our approach enables the direct visualization of HSC behaviours and dissection of heterogeneity in HSC niches.


A dual genetic strategy enables the labelling and in vivo imaging of native long-term haematopoietic stem cells in the mouse calvarial bone marrow.


  
Pathway paradigms revealed from the genetics of inflammatory bowel disease 期刊论文
NATURE, 2020, 578 (7796) : 527-539
作者:  Yu, Kwanha;  Lin, Chia-Ching John;  Hatcher, Asante;  Lozzi, Brittney;  Kong, Kathleen;  Huang-Hobbs, Emmet;  Cheng, Yi-Ting;  Beechar, Vivek B.;  Zhu, Wenyi;  Zhang, Yiqun;  Chen, Fengju;  Mills, Gordon B.;  Mohila, Carrie A.;  Creighton, Chad J.;  Noebels, Jeffrey L.;  Scott, Kenneth L.;  Deneen, Benjamin
收藏  |  浏览/下载:7/0  |  提交时间:2020/07/03

Inflammatory bowel disease (IBD) is a complex genetic disease that is instigated and amplified by the confluence of multiple genetic and environmental variables that perturb the immune-microbiome axis. The challenge of dissecting pathological mechanisms underlying IBD has led to the development of transformative approaches in human genetics and functional genomics. Here we describe IBD as a model disease in the context of leveraging human genetics to dissect interactions in cellular and molecular pathways that regulate homeostasis of the mucosal immune system. Finally, we synthesize emerging insights from multiple experimental approaches into pathway paradigms and discuss future prospects for disease-subtype classification and therapeutic intervention.


This Review examines inflammatory bowel disease in the context of human genetics studies that help to identify pathways that regulate homeostasis of the mucosal immune system and discusses future prospects for disease-subtype classification and therapeutic intervention.