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Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants 期刊论文
Science, 2021
作者:  Lingshu Wang;  Tongqing Zhou;  Yi Zhang;  Eun Sung Yang;  Chaim A. Schramm;  Wei Shi;  Amarendra Pegu;  Olamide K. Oloniniyi;  Amy R. Henry;  Samuel Darko;  Sandeep R. Narpala;  Christian Hatcher;  David R. Martinez;  Yaroslav Tsybovsky;  Emily Phung;  Olubukola M. Abiona;  Avan Antia;  Evan M. Cale;  Lauren A. Chang;  Misook Choe;  Kizzmekia S. Corbett;  Rachel L. Davis;  Anthony T. DiPiazza;  Ingelise J. Gordon;  Sabrina Helmold Hait;  Tandile Hermanus;  Prudence Kgagudi;  Farida Laboune;  Kwanyee Leung;  Tracy Liu;  Rosemarie D. Mason;  Alexandra F. Nazzari;  Laura Novik;  Sarah O’Connell;  Sijy O’Dell;  Adam S. Olia;  Stephen D. Schmidt;  Tyler Stephens;  Christopher D. Stringham;  Chloe Adrienna Talana;  I-Ting Teng;  Danielle A. Wagner;  Alicia T. Widge;  Baoshan Zhang;  Mario Roederer;  Julie E. Ledgerwood;  Tracy J. Ruckwardt;  Martin R. Gaudinski;  Penny L. Moore;  Nicole A. Doria-Rose;  Ralph S. Baric;  Barney S. Graham;  Adrian B. McDermott;  Daniel C. Douek;  Peter D. Kwong;  John R. Mascola;  Nancy J. Sullivan;  John Misasi
收藏  |  浏览/下载:19/0  |  提交时间:2021/08/17
Computational social science: Obstacles and opportunities 期刊论文
Science, 2020
作者:  David M. J. Lazer;  Alex Pentland;  Duncan J. Watts;  Sinan Aral;  Susan Athey;  Noshir Contractor;  Deen Freelon;  Sandra Gonzalez-Bailon;  Gary King;  Helen Margetts;  Alondra Nelson;  Matthew J. Salganik;  Markus Strohmaier;  Alessandro Vespignani;  Claudia Wagner
收藏  |  浏览/下载:13/0  |  提交时间:2020/09/08
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:5/0  |  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.


  
The projected timing of abrupt ecological disruption from climate change 期刊论文
NATURE, 2020, 580 (7804) : 496-+
作者:  Gorgulla, Christoph;  Boeszoermenyi, Andras;  Wang, Zi-Fu;  Fischer, Patrick D.;  Coote, Paul W.;  Padmanabha Das, Krishna M.;  Malets, Yehor S.;  Radchenko, Dmytro S.;  Moroz, Yurii S.;  Scott, David A.;  Fackeldey, Konstantin;  Hoffmann, Moritz;  Iavniuk, Iryna;  Wagner, Gerhard;  Arthanari, Haribabu
收藏  |  浏览/下载:53/0  |  提交时间:2020/05/13

As anthropogenic climate change continues the risks to biodiversity will increase over time, with future projections indicating that a potentially catastrophic loss of global biodiversity is on the horizon(1-3). However, our understanding of when and how abruptly this climate-driven disruption of biodiversity will occur is limited because biodiversity forecasts typically focus on individual snapshots of the future. Here we use annual projections (from 1850 to 2100) of temperature and precipitation across the ranges of more than 30,000 marine and terrestrial species to estimate the timing of their exposure to potentially dangerous climate conditions. We project that future disruption of ecological assemblages as a result of climate change will be abrupt, because within any given ecological assemblage the exposure of most species to climate conditions beyond their realized niche limits occurs almost simultaneously. Under a high-emissions scenario (representative concentration pathway (RCP) 8.5), such abrupt exposure events begin before 2030 in tropical oceans and spread to tropical forests and higher latitudes by 2050. If global warming is kept below 2 degrees C, less than 2% of assemblages globally are projected to undergo abrupt exposure events of more than 20% of their constituent species  however, the risk accelerates with the magnitude of warming, threatening 15% of assemblages at 4 degrees C, with similar levels of risk in protected and unprotected areas. These results highlight the impending risk of sudden and severe biodiversity losses from climate change and provide a framework for predicting both when and where these events may occur.


Using annual projections of temperature and precipitation to estimate when species will be exposed to potentially harmful climate conditions reveals that disruption of ecological assemblages as a result of climate change will be abrupt and could start as early as the current decade.


  
Structure of the M2 muscarinic receptor-beta-arrestin complex in a lipid nanodisc 期刊论文
NATURE, 2020, 579 (7798) : 297-+
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:28/0  |  提交时间:2020/07/03

After activation by an agonist, G-protein-coupled receptors (GPCRs) recruit beta-arrestin, which desensitizes heterotrimeric G-protein signalling and promotes receptor endocytosis(1). Additionally, beta-arrestin directly regulates many cell signalling pathways that can induce cellular responses distinct from that of G proteins(2). In contrast to G proteins, for which there are many high-resolution structures in complex with GPCRs, the molecular mechanisms underlying the interaction of beta-arrestin with GPCRs are much less understood. Here we present a cryo-electron microscopy structure of beta-arrestin 1 (beta arr1) in complex with M2 muscarinic receptor (M2R) reconstituted in lipid nanodiscs. The M2R-beta arr1 complex displays a multimodal network of flexible interactions, including binding of the N domain of beta arr1 to phosphorylated receptor residues and insertion of the finger loop of beta arr1 into the M2R seven-transmembrane bundle, which adopts a conformation similar to that in the M2R-heterotrimeric G(o) protein complex(3). Moreover, the cryo-electron microscopy map reveals that the C-edge of beta arr1 engages the lipid bilayer. Through atomistic simulations and biophysical, biochemical and cellular assays, we show that the C-edge is critical for stable complex formation, beta arr1 recruitment, receptor internalization, and desensitization of G-protein activation. Taken together, these data suggest that the cooperative interactions of beta-arrestin with both the receptor and the phospholipid bilayer contribute to its functional versatility.


  
Tobacco smoking and somatic mutations in human bronchial epithelium 期刊论文
NATURE, 2020, 578 (7794) : 266-+
作者:  Sharma, Nikhil;  Flaherty, Kali;  Lezgiyeva, Karina;  Wagner, Daniel E.;  Klein, Allon M.;  Ginty, David D.
收藏  |  浏览/下载:32/0  |  提交时间:2020/07/03

Whole-genome sequencing of normal bronchial epithelium from 16 individuals shows that tobacco smoking increases genomic heterogeneity, mutational burden and driver mutations, whereas stopping smoking promotes replenishment of the epithelium with near-normal cells.


Tobacco smoking causes lung cancer(1-3), a process that is driven by more than 60 carcinogens in cigarette smoke that directly damage and mutate DNA(4,5). The profound effects of tobacco on the genome of lung cancer cells are well-documented(6-10), but equivalent data for normal bronchial cells are lacking. Here we sequenced whole genomes of 632 colonies derived from single bronchial epithelial cells across 16 subjects. Tobacco smoking was the major influence on mutational burden, typically adding from 1,000 to 10,000 mutations per cell  massively increasing the variance both within and between subjects  and generating several distinct mutational signatures of substitutions and of insertions and deletions. A population of cells in individuals with a history of smoking had mutational burdens that were equivalent to those expected for people who had never smoked: these cells had less damage from tobacco-specific mutational processes, were fourfold more frequent in ex-smokers than current smokers and had considerably longer telomeres than their more-mutated counterparts. Driver mutations increased in frequency with age, affecting 4-14% of cells in middle-aged subjects who had never smoked. In current smokers, at least 25% of cells carried driver mutations and 0-6% of cells had two or even three drivers. Thus, tobacco smoking increases mutational burden, cell-to-cell heterogeneity and driver mutations, but quitting promotes replenishment of the bronchial epithelium from mitotically quiescent cells that have avoided tobacco mutagenesis.


  
The emergence of transcriptional identity in somatosensory neurons 期刊论文
NATURE, 2020, 577 (7790) : 392-+
作者:  Sharma, Nikhil;  Flaherty, Kali;  Lezgiyeva, Karina;  Wagner, Daniel E.;  Klein, Allon M.;  Ginty, David D.
收藏  |  浏览/下载:5/0  |  提交时间:2020/07/03

More than twelve morphologically and physiologically distinct subtypes of primary somatosensory neuron report salient features of our internal and external environments(1-4). It is unclear how specialized gene expression programs emerge during development to endow these subtypes with their unique properties. To assess the developmental progression of transcriptional maturation of each subtype of principal somatosensory neuron, we generated a transcriptomic atlas of cells traversing the primary somatosensory neuron lineage in mice. Here we show that somatosensory neurogenesis gives rise to neurons in a transcriptionally unspecialized state, characterized by co-expression of transcription factors that become restricted to select subtypes as development proceeds. Single-cell transcriptomic analyses of sensory neurons from mutant mice lacking transcription factors suggest that these broad-to-restricted transcription factors coordinate subtype-specific gene expression programs in subtypes in which their expression is maintained. We also show that neuronal targets are involved in this process  disruption of the prototypic target-derived neurotrophic factor NGF leads to aberrant subtype-restricted patterns of transcription factor expression. Our findings support a model in which cues that emanate from intermediate and final target fields promote neuronal diversification in part by transitioning cells from a transcriptionally unspecialized state to transcriptionally distinct subtypes by modulating the selection of subtype-restricted transcription factors.


  
Quantum crystal structure in the 250-kelvin superconducting lanthanum hydride 期刊论文
NATURE, 2020, 578 (7793) : 66-+
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:19/0  |  提交时间:2020/07/03

The discovery of superconductivity at 200 kelvin in the hydrogen sulfide system at high pressures(1) demonstrated the potential of hydrogen-rich materials as high-temperature superconductors. Recent theoretical predictions of rare-earth hydrides with hydrogen cages(2,3) and the subsequent synthesis of LaH10 with a superconducting critical temperature (T-c) of 250 kelvin(4,5) have placed these materials on the verge of achieving the long-standing goal of room-temperature superconductivity. Electrical and X-ray diffraction measurements have revealed a weakly pressure-dependent T-c for LaH10 between 137 and 218 gigapascals in a structure that has a face-centred cubic arrangement of lanthanum atoms(5). Here we show that quantum atomic fluctuations stabilize a highly symmetrical Fm (3) over barm crystal structure over this pressure range. The structure is consistent with experimental findings and has a very large electron-phonon coupling constant of 3.5. Although ab initio classical calculations predict that this Fm (3) over barm structure undergoes distortion at pressures below 230 gigapascals(2,3,) yielding a complex energy landscape, the inclusion of quantum effects suggests that it is the true ground-state structure. The agreement between the calculated and experimental Tc values further indicates that this phase is responsible for the superconductivity observed at 250 kelvin. The relevance of quantum fluctuations calls into question many of the crystal structure predictions that have been made for hydrides within a classical approach and that currently guide the experimental quest for room-temperature superconductivity(6-8). Furthermore, we find that quantum effects are crucial for the stabilization of solids with high electron-phonon coupling constants that could otherwise be destabilized by the large electron-phonon interaction(9), thus reducing the pressures required for their synthesis.


  
Climate-driven reduction of genetic variation in plant phenology alters soil communities and nutrient pools 期刊论文
GLOBAL CHANGE BIOLOGY, 2019, 25 (4) : 1514-1528
作者:  Ware, Ian M.;  Van Nuland, Michael E.;  Schweitzer, Jennifer A.;  Yang, Zamin;  Schadt, Christopher W.;  Sidak-Loftis, Lindsay C.;  Stone, Nathan E.;  Busch, Joseph D.;  Wagner, David M.;  Bailey, Joseph K.
收藏  |  浏览/下载:8/0  |  提交时间:2019/04/09
climate  ecosystem dynamics  genetic divergence  intraspecific variation  phenology  Populus  
Overview: Precipitation characteristics and sensitivities to environmental conditions during GoAmazon2014/5 and ACRIDICON-CHUVA 期刊论文
ATMOSPHERIC CHEMISTRY AND PHYSICS, 2018, 18 (9) : 6461-6482
作者:  Machado, Luiz A. T.;  Calheiros, Alan J. P.;  Biscaro, Thiago;  Giangrande, Scott;  Silva Dias, Maria A. F.;  Cecchini, Micael A.;  Albrecht, Rachel;  Andreae, Meinrat O.;  Araujo, Wagner F.;  Artaxo, Paulo;  Borrmann, Stephan;  Braga, Ramon;  Burleyson, Casey;  Eichholz, Cristiano W.;  Fan, Jiwen;  Feng, Zhe;  Fisch, Gilberto F.;  Jensen, Michael P.;  Martin, Scot T.;  Poeschl, Ulrich;  Poehlker, Christopher;  Poehlker, Mira L.;  Ribaud, Jean-Francois;  Rosenfeld, Daniel;  Saraiva, Jaci M. B.;  Schumacher, Courtney;  Thalman, Ryan;  Walter, David;  Wendisch, Manfred
收藏  |  浏览/下载:7/0  |  提交时间:2019/04/09