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Autosomal dominant VCP hypomorph mutation impairs disaggregation of PHF-tau 期刊论文
Science, 2020
作者:  Nabil F. Darwich;  Jessica M. Phan;  Boram Kim;  EunRan Suh;  John D. Papatriantafyllou;  Lakshmi Changolkar;  Aivi T. Nguyen;  Caroline M. O’Rourke;  Zhuohao He;  Sílvia Porta;  Garrett S. Gibbons;  Kelvin C. Luk;  Sokratis G. Papageorgiou;  Murray Grossman;  Lauren Massimo;  David J. Irwin;  Corey T. McMillan;  Ilya M. Nasrallah;  Camilo Toro;  Geoffrey K. Aguirre;  Vivianna M. Van Deerlin;  Edward B. Lee
收藏  |  浏览/下载:9/0  |  提交时间:2020/11/24
Spatial patterns and trends of summertime low cloudiness for the Pacific Northwest, 1996‐2017 期刊论文
Geophysical Research Letters, 2020
作者:  Alex W. Dye;  Bharat Rastogi;  Rachel E. S. Clemesha;  John B. Kim;  Roger M. Samelson;  Christopher J. Still;  A. Park Williams
收藏  |  浏览/下载:8/0  |  提交时间:2020/08/18
Agricultural acceleration of soil carbonate weathering 期刊论文
Global Change Biology, 2020
作者:  John H. Kim;  Esteban G. Jobbá;  gy;  Daniel D. Richter;  Susan E. Trumbore;  Robert B. Jackson
收藏  |  浏览/下载:21/0  |  提交时间:2020/08/09
Constraining remote oxidation capacity with ATom observations 期刊论文
ATMOSPHERIC CHEMISTRY AND PHYSICS, 2020, 20 (13) : 7753-7781
作者:  Travis, Katherine R.;  Heald, Colette L.;  Allen, Hannah M.;  Apel, Eric C.;  Arnold, Stephen R.;  Blake, Donald R.;  Brune, William H.;  Chen, Xin;  Commane, Roisin;  Crounse, John D.;  Daube, Bruce C.;  Diskin, Glenn S.;  Elkins, James W.;  Evans, Mathew J.;  Hall, Samuel R.;  Hintsa, Eric J.;  Hornbrook, Rebecca S.;  Kasibhatla, Prasad S.;  Kim, Michelle J.;  Luo, Gan;  McKain, Kathryn;  Millet, Dylan B.;  Moore, Fred L.;  Peischl, Jeffrey;  Ryerson, Thomas B.;  Sherwen, Tomas;  Thames, Alexander B.;  Ullmann, Kirk;  Wang, Xuan;  Wennberg, Paul O.;  Wolfe, Glenn M.;  Yu, Fangqun
收藏  |  浏览/下载:49/0  |  提交时间:2020/08/18
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.


  
Missing OH reactivity in the global marine boundary layer 期刊论文
ATMOSPHERIC CHEMISTRY AND PHYSICS, 2020, 20 (6) : 4013-4029
作者:  Thames, Alexander B.;  Brune, William H.;  Miller, David O.;  Allen, Hannah M.;  Apel, Eric C.;  Blake, Donald R.;  Bui, T. Paul;  Commane, Roisin;  Crounse, John D.;  Daube, Bruce C.;  Diskin, Glenn S.;  DiGangi, Joshua P.;  Elkins, JamesW.;  Hall, Samuel R.;  Hanisco, Thomas F.;  Hannun, Reem A.;  Hintsa, Eric;  Hornbrook, Rebecca S.;  Kim, Michelle J.;  McKain, Kathryn;  Moore, Fred L.;  Nicely, Julie M.;  Peischl, Jeffrey;  Ryerson, Thomas B.;  St Clair, Jason M.;  Sweeney, Colm;  Teng, Alex;  Thompson, Chelsea R.;  Ullmann, Kirk;  Wennberg, Paul O.;  Wolfe, Glenn M.
收藏  |  浏览/下载:14/0  |  提交时间:2020/07/02
A lysosomal switch triggers proteostasis renewal in the immortal C. elegans germ lineage (vol 551, pg 629, 2017) 期刊论文
NATURE, 2020, 580 (7802) : E5-E5
作者:  Lu, Zhihao;  Zou, Jianling;  Li, Shuang;  Topper, Michael J.;  Tao, Yong;  Zhang, Hao;  Jiao, Xi;  Xie, Wenbing;  Kong, Xiangqian;  Vaz, Michelle;  Li, Huili;  Cai, Yi;  Xia, Limin;  Huang, Peng;  Rodgers, Kristen;  Lee, Beverly;  Riemer, Joanne B.;  Day, Chi-Ping;  Yen, Ray-Whay Chiu;  Cui, Ying;  Wang, Yujiao;  Wang, Yanni;  Zhang, Weiqiang;  Easwaran, Hariharan;  Hulbert, Alicia;  Kim, KiBem;  Juergens, Rosalyn A.;  Yang, Stephen C.;  Battafarano, Richard J.;  Bush, Errol L.;  Broderick, Stephen R.;  Cattaneo, Stephen M.;  Brahmer, Julie R.;  Rudin, Charles M.;  Wrangle, John;  Mei, Yuping;  Kim, Young J.;  Zhang, Bin;  Wang, Ken Kang-Hsin;  Forde, Patrick M.;  Margolick, Joseph B.;  Nelkin, Barry D.;  Zahnow, Cynthia A.;  Pardoll, Drew M.;  Housseau, Franck;  Baylin, Stephen B.;  Shen, Lin;  Brock, Malcolm V.
收藏  |  浏览/下载:27/0  |  提交时间:2020/07/03
Nightside condensation of iron in an ultrahot giant exoplanet 期刊论文
NATURE, 2020, 580 (7805) : 597-+
作者:  Lu, Zhihao;  Zou, Jianling;  Li, Shuang;  Topper, Michael J.;  Tao, Yong;  Zhang, Hao;  Jiao, Xi;  Xie, Wenbing;  Kong, Xiangqian;  Vaz, Michelle;  Li, Huili;  Cai, Yi;  Xia, Limin;  Huang, Peng;  Rodgers, Kristen;  Lee, Beverly;  Riemer, Joanne B.;  Day, Chi-Ping;  Yen, Ray-Whay Chiu;  Cui, Ying;  Wang, Yujiao;  Wang, Yanni;  Zhang, Weiqiang;  Easwaran, Hariharan;  Hulbert, Alicia;  Kim, KiBem;  Juergens, Rosalyn A.;  Yang, Stephen C.;  Battafarano, Richard J.;  Bush, Errol L.;  Broderick, Stephen R.;  Cattaneo, Stephen M.;  Brahmer, Julie R.;  Rudin, Charles M.;  Wrangle, John;  Mei, Yuping;  Kim, Young J.;  Zhang, Bin;  Wang, Ken Kang-Hsin;  Forde, Patrick M.;  Margolick, Joseph B.;  Nelkin, Barry D.;  Zahnow, Cynthia A.;  Pardoll, Drew M.;  Housseau, Franck;  Baylin, Stephen B.;  Shen, Lin;  Brock, Malcolm V.
收藏  |  浏览/下载:58/0  |  提交时间:2020/07/03

Ultrahot giant exoplanets receive thousands of times Earth'  s insolation(1,2). Their high-temperature atmospheres (greater than 2,000 kelvin) are ideal laboratories for studying extreme planetary climates and chemistry(3-5). Daysides are predicted to be cloud-free, dominated by atomic species(6) and much hotter than nightsides(5,7,8). Atoms are expected to recombine into molecules over the nightside(9), resulting in different day and night chemistries. Although metallic elements and a large temperature contrast have been observed(10-14), no chemical gradient has been measured across the surface of such an exoplanet. Different atmospheric chemistry between the day-to-night ('  evening'  ) and night-to-day ('  morning'  ) terminators could, however, be revealed as an asymmetric absorption signature during transit(4,7,15). Here we report the detection of an asymmetric atmospheric signature in the ultrahot exoplanet WASP-76b. We spectrally and temporally resolve this signature using a combination of high-dispersion spectroscopy with a large photon-collecting area. The absorption signal, attributed to neutral iron, is blueshifted by -11 +/- 0.7 kilometres per second on the trailing limb, which can be explained by a combination of planetary rotation and wind blowing from the hot dayside(16). In contrast, no signal arises from the nightside close to the morning terminator, showing that atomic iron is not absorbing starlight there. We conclude that iron must therefore condense during its journey across the nightside.


Absorption lines of iron in the dayside atmosphere of an ultrahot giant exoplanet disappear after travelling across the nightside, showing that the iron has condensed during its travel.


  
Ice front blocking of ocean heat transport to an Antarctic ice shelf 期刊论文
NATURE, 2020, 578 (7796) : 568-+
作者:  Alexandrov, Ludmil B.;  Kim, Jaegil;  Haradhvala, Nicholas J.;  Huang, Mi Ni;  Ng, Alvin Wei Tian;  Wu, Yang;  Boot, Arnoud;  Covington, Kyle R.;  Gordenin, Dmitry A.;  Bergstrom, Erik N.;  Islam, S. M. Ashiqul;  Lopez-Bigas, Nuria;  Klimczak, Leszek J.;  McPherson, John R.;  Morganella, Sandro;  Sabarinathan, Radhakrishnan;  Wheeler, David A.;  Mustonen, Ville;  Getz, Gad;  Rozen, Steven G.;  Stratton, Michael R.
收藏  |  浏览/下载:12/0  |  提交时间:2020/05/13

The front of the Getz Ice Shelf in West Antarctica creates an abrupt topographic step that deflects ocean currents, suppressing 70% of the heat delivery to the ice sheet.


Mass loss from the Antarctic Ice Sheet to the ocean has increased in recent decades, largely because the thinning of its floating ice shelves has allowed the outflow of grounded ice to accelerate(1,2). Enhanced basal melting of the ice shelves is thought to be the ultimate driver of change(2,3), motivating a recent focus on the processes that control ocean heat transport onto and across the seabed of the Antarctic continental shelf towards the ice(4-6). However, the shoreward heat flux typically far exceeds that required to match observed melt rates(2,7,8), suggesting that other critical controls exist. Here we show that the depth-independent (barotropic) component of the heat flow towards an ice shelf is blocked by the marked step shape of the ice front, and that only the depth-varying (baroclinic) component, which is typically much smaller, can enter the sub-ice cavity. Our results arise from direct observations of the Getz Ice Shelf system and laboratory experiments on a rotating platform. A similar blocking of the barotropic component may occur in other areas with comparable ice-bathymetry configurations, which may explain why changes in the density structure of the water column have been found to be a better indicator of basal melt rate variability than the heat transported onto the continental shelf(9). Representing the step topography of the ice front accurately in models is thus important for simulating ocean heat fluxes and induced melt rates.


  
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.