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Astronaut with sights on Mars 期刊论文
NATURE, 2020, 581 (7809) : 367-367
作者:  Funabashi, Masanori;  Grove, Tyler L.;  Wang, Min;  Varma, Yug;  McFadden, Molly E.;  Brown, Laura C.;  Guo, Chunjun;  Higginbottom, Steven;  Almo, Steven C.;  Fischbach, Michael A.
收藏  |  浏览/下载:19/0  |  提交时间:2020/07/03

NASA astronaut Jessica Watkins is at the forefront of a new crop of space explorers destined for the Moon, and maybe one day, Mars.


NASA astronaut Jessica Watkins is at the forefront of a new crop of space explorers destined for the Moon, and maybe one day, Mars.


  
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.


  
Impaired cell fate through gain-of-function mutations in a chromatin reader 期刊论文
NATURE, 2020, 577 (7788) : 121-+
作者:  Wan, Liling;  Chong, Shasha;  Xuan, Fan;  Liang, Angela;  Cui, Xiaodong;  Gates, Leah;  Carroll, Thomas S.;  Li, Yuanyuan;  Feng, Lijuan;  Chen, Guochao;  Wang, Shu-Ping;  Ortiz, Michael V.;  Daley, Sara K.;  Wang, Xiaolu;  Xuan, Hongwen;  Kentsis, Alex;  Muir, Tom W.;  Roeder, Robert G.;  Li, Haitao;  Li, Wei;  Tjian, Robert;  Wen, Hong;  Allis, C. David
收藏  |  浏览/下载:11/0  |  提交时间:2020/07/03

Modifications of histone proteins have essential roles in normal development and human disease. Recognition of modified histones by '  reader'  proteins is a key mechanism that mediates the function of histone modifications, but how the dysregulation of these readers might contribute to disease remains poorly understood. We previously identified the ENL protein as a reader of histone acetylation via its YEATS domain, linking it to the expression of cancer-driving genes in acute leukaemia1. Recurrent hotspot mutations have been found in the ENL YEATS domain in Wilms tumour2,3, the most common type of paediatric kidney cancer. Here we show, using human and mouse cells, that these mutations impair cell-fate regulation by conferring gain-of-function in chromatin recruitment and transcriptional control. ENL mutants induce gene-expression changes that favour a premalignant cell fate, and, in an assay for nephrogenesis using murine cells, result in undifferentiated structures resembling those observed in human Wilms tumour. Mechanistically, although bound to largely similar genomic loci as the wild-type protein, ENL mutants exhibit increased occupancy at a subset of targets, leading to a marked increase in the recruitment and activity of transcription elongation machinery that enforces active transcription from target loci. Furthermore, ectopically expressed ENL mutants exhibit greater self-association and form discrete and dynamic nuclear puncta that are characteristic of biomolecular hubs consisting of local high concentrations of regulatory factors. Such mutation-driven ENL self-association is functionally linked to enhanced chromatin occupancy and gene activation. Collectively, our findings show that hotspot mutations in a chromatinreader domain drive self-reinforced recruitment, derailing normal cell-fate control during development and leading to an oncogenic outcome.


  
Highly porous nature of a primitive asteroid revealed by thermal imaging 期刊论文
NATURE, 2020, 579 (7800) : 518-522
作者:  Quinn, Robert A.;  Melnik, Alexey, V;  Vrbanac, Alison;  Fu, Ting;  Patras, Kathryn A.;  Christy, Mitchell P.;  Bodai, Zsolt;  Belda-Ferre, Pedro;  Tripathi, Anupriya;  Chung, Lawton K.;  Downes, Michael;  Welch, Ryan D.;  Quinn, Melissa;  Humphrey, Greg;  Panitchpakdi, Morgan;  Weldon, Kelly C.;  Aksenov, Alexander;  da Silva, Ricardo;  Avila-Pacheco, Julian;  Clish, Clary;  Bae, Sena;  Mallick, Himel;  Franzosa, Eric A.;  Lloyd-Price, Jason;  Bussell, Robert;  Thron, Taren;  Nelson, Andrew T.;  Wang, Mingxun;  Leszczynski, Eric;  Vargas, Fernando;  Gauglitz, Julia M.;  Meehan, Michael J.;  Gentry, Emily;  Arthur, Timothy D.;  Komor, Alexis C.;  Poulsen, Orit;  Boland, Brigid S.;  Chang, John T.;  Sandborn, William J.;  Lim, Meerana;  Garg, Neha;  Lumeng, Julie C.;  Xavier, Ramnik J.;  Kazmierczak, Barbara, I;  Jain, Ruchi;  Egan, Marie;  Rhee, Kyung E.;  Ferguson, David;  Raffatellu, Manuela;  Vlamakis, Hera;  Haddad, Gabriel G.;  Siegel, Dionicio;  Huttenhower, Curtis;  Mazmanian, Sarkis K.;  Evans, Ronald M.;  Nizet, Victor;  Knight, Rob;  Dorrestein, Pieter C.
收藏  |  浏览/下载:49/0  |  提交时间:2020/05/13

Carbonaceous (C-type) asteroids(1) are relics of the early Solar System that have preserved primitive materials since their formation approximately 4.6 billion years ago. They are probably analogues of carbonaceous chondrites(2,3) and are essential for understanding planetary formation processes. However, their physical properties remain poorly known because carbonaceous chondrite meteoroids tend not to survive entry to Earth'  s atmosphere. Here we report on global one-rotation thermographic images of the C-type asteroid 162173 Ryugu, taken by the thermal infrared imager (TIR)(4) onboard the spacecraft Hayabusa2(5), indicating that the asteroid'  s boulders and their surroundings have similar temperatures, with a derived thermal inertia of about 300 J m(-2) s(-0.5) K-1 (300 tiu). Contrary to predictions that the surface consists of regolith and dense boulders, this low thermal inertia suggests that the boulders are more porous than typical carbonaceous chondrites(6) and that their surroundings are covered with porous fragments more than 10 centimetres in diameter. Close-up thermal images confirm the presence of such porous fragments and the flat diurnal temperature profiles suggest a strong surface roughness effect(7,8). We also observed in the close-up thermal images boulders that are colder during the day, with thermal inertia exceeding 600 tiu, corresponding to dense boulders similar to typical carbonaceous chondrites(6). These results constrain the formation history of Ryugu: the asteroid must be a rubble pile formed from impact fragments of a parent body with microporosity(9) of approximately 30 to 50 per cent that experienced a low degree of consolidation. The dense boulders might have originated from the consolidated innermost region or they may have an exogenic origin. This high-porosity asteroid may link cosmic fluffy dust to dense celestial bodies(10).


Thermal imaging data obtained from the spacecraft Hayabusa2 reveal that the carbonaceous asteroid 162173 Ryugu is an object of unusually high porosity.


  
A conserved dendritic-cell regulatory program limits antitumour immunity 期刊论文
NATURE, 2020, 580 (7802) : 257-+
作者:  Perry, Rachel J.;  Zhang, Dongyan;  Guerra, Mateus T.;  Brill, Allison L.;  Goedeke, Leigh;  Nasiri, Ali R.;  Rabin-Court, Aviva;  Wang, Yongliang;  Peng, Liang;  Dufour, Sylvie;  Zhang, Ye;  Zhang, Xian-Man;  Butrico, Gina M.;  Toussaint, Keshia;  Nozaki, Yuichi;  Cline, Gary W.;  Petersen, Kitt Falk;  Nathanson, Michael H.;  Ehrlich, Barbara E.;  Shulman, Gerald I.
收藏  |  浏览/下载:27/0  |  提交时间:2020/07/03

After taking up tumour-associated antigens, dendritic cells in mouse and human tumours upregulate a regulatory gene program that limits dendritic cell immunostimulatory function, and modulating this program can rescue antitumor immunity in mice.


Checkpoint blockade therapies have improved cancer treatment, but such immunotherapy regimens fail in a large subset of patients. Conventional type 1 dendritic cells (DC1s) control the response to checkpoint blockade in preclinical models and are associated with better overall survival in patients with cancer, reflecting the specialized ability of these cells to prime the responses of CD8(+) T cells(1-3). Paradoxically, however, DC1s can be found in tumours that resist checkpoint blockade, suggesting that the functions of these cells may be altered in some lesions. Here, using single-cell RNA sequencing in human and mouse non-small-cell lung cancers, we identify a cluster of dendritic cells (DCs) that we name '  mature DCs enriched in immunoregulatory molecules'  (mregDCs), owing to their coexpression of immunoregulatory genes (Cd274, Pdcd1lg2 and Cd200) and maturation genes (Cd40, Ccr7 and Il12b). We find that the mregDC program is expressed by canonical DC1s and DC2s upon uptake of tumour antigens. We further find that upregulation of the programmed death ligand 1 protein-a key checkpoint molecule-in mregDCs is induced by the receptor tyrosine kinase AXL, while upregulation of interleukin (IL)-12 depends strictly on interferon-gamma and is controlled negatively by IL-4 signalling. Blocking IL-4 enhances IL-12 production by tumour-antigen-bearing mregDC1s, expands the pool of tumour-infiltrating effector T cells and reduces tumour burden. We have therefore uncovered a regulatory module associated with tumour-antigen uptake that reduces DC1 functionality in human and mouse cancers.


  
A genomic and epigenomic atlas of prostate cancer in Asian populations 期刊论文
NATURE, 2020: 93-+
作者:  Perry, Rachel J.;  Zhang, Dongyan;  Guerra, Mateus T.;  Brill, Allison L.;  Goedeke, Leigh;  Nasiri, Ali R.;  Rabin-Court, Aviva;  Wang, Yongliang;  Peng, Liang;  Dufour, Sylvie;  Zhang, Ye;  Zhang, Xian-Man;  Butrico, Gina M.;  Toussaint, Keshia;  Nozaki, Yuichi;  Cline, Gary W.;  Petersen, Kitt Falk;  Nathanson, Michael H.;  Ehrlich, Barbara E.;  Shulman, Gerald I.
收藏  |  浏览/下载:33/0  |  提交时间:2020/07/03

Prostate cancer is the second most common cancer in men worldwide(1). Over the past decade, large-scale integrative genomics efforts have enhanced our understanding of this disease by characterizing its genetic and epigenetic landscape in thousands of patients(2,3). However, most tumours profiled in these studies were obtained from patients from Western populations. Here we produced and analysed whole-genome, whole-transcriptome and DNA methylation data for 208 pairs of tumour tissue samples and matched healthy control tissue from Chinese patients with primary prostate cancer. Systematic comparison with published data from 2,554 prostate tumours revealed that the genomic alteration signatures in Chinese patients were markedly distinct from those of Western cohorts: specifically, 41% of tumours contained mutations in FOXA1 and 18% each had deletions in ZNF292 and CHD1. Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression. Coding and noncoding mutations, as well as epimutations, converged on pathways that are important for prostate cancer, providing insights into this devastating disease. These discoveries underscore the importance of including population context in constructing comprehensive genomic maps for disease.


Genomic, transcriptomic and DNA methylation data from tissue samples from 208 Chinese patients with prostate cancer define the landscape of alterations in this population, and comparison with data from Western cohorts suggests that the disease may stratify into different molecular subtypes.


  
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.


  
Experimental demonstration of memory-enhanced quantum communication 期刊论文
NATURE, 2020
作者:  Quinn, Robert A.;  Melnik, Alexey, V;  Vrbanac, Alison;  Fu, Ting;  Patras, Kathryn A.;  Christy, Mitchell P.;  Bodai, Zsolt;  Belda-Ferre, Pedro;  Tripathi, Anupriya;  Chung, Lawton K.;  Downes, Michael;  Welch, Ryan D.;  Quinn, Melissa;  Humphrey, Greg;  Panitchpakdi, Morgan;  Weldon, Kelly C.;  Aksenov, Alexander;  da Silva, Ricardo;  Avila-Pacheco, Julian;  Clish, Clary;  Bae, Sena;  Mallick, Himel;  Franzosa, Eric A.;  Lloyd-Price, Jason;  Bussell, Robert;  Thron, Taren;  Nelson, Andrew T.;  Wang, Mingxun;  Leszczynski, Eric;  Vargas, Fernando;  Gauglitz, Julia M.;  Meehan, Michael J.;  Gentry, Emily;  Arthur, Timothy D.;  Komor, Alexis C.;  Poulsen, Orit;  Boland, Brigid S.;  Chang, John T.;  Sandborn, William J.;  Lim, Meerana;  Garg, Neha;  Lumeng, Julie C.;  Xavier, Ramnik J.;  Kazmierczak, Barbara, I;  Jain, Ruchi;  Egan, Marie;  Rhee, Kyung E.;  Ferguson, David;  Raffatellu, Manuela;  Vlamakis, Hera;  Haddad, Gabriel G.;  Siegel, Dionicio;  Huttenhower, Curtis;  Mazmanian, Sarkis K.;  Evans, Ronald M.;  Nizet, Victor;  Knight, Rob;  Dorrestein, Pieter C.
收藏  |  浏览/下载:36/0  |  提交时间:2020/07/03

The ability to communicate quantum information over long distances is of central importance in quantum science and engineering(1). Although some applications of quantum communication such as secure quantum key distribution(2,3) are already being successfully deployed(4-7), their range is currently limited by photon losses and cannot be extended using straightforward measure-and-repeat strategies without compromising unconditional security(8). Alternatively, quantum repeaters(9), which utilize intermediate quantum memory nodes and error correction techniques, can extend the range of quantum channels. However, their implementation remains an outstanding challenge(10-16), requiring a combination of efficient and high-fidelity quantum memories, gate operations, and measurements. Here we use a single solid-state spin memory integrated in a nanophotonic diamond resonator(17-19) to implement asynchronous photonic Bell-state measurements, which are a key component of quantum repeaters. In a proof-of-principle experiment, we demonstrate high-fidelity operation that effectively enables quantum communication at a rate that surpasses the ideal loss-equivalent direct-transmission method while operating at megahertz clock speeds. These results represent a crucial step towards practical quantum repeaters and large-scale quantum networks(20,21).


A solid-state spin memory is used to demonstrate quantum repeater functionality, which has the potential to overcome photon losses involved in long-distance transmission of quantum information.


  
Current-driven magnetic domain-wall logic 期刊论文
NATURE, 2020, 579 (7798) : 214-+
作者:  Culp, Elizabeth J.;  Waglechner, Nicholas;  Wang, Wenliang;  Fiebig-Comyn, Aline A.;  Hsu, Yen-Pang;  Koteva, Kalinka;  Sychantha, David;  Coombes, Brian K.;  Van Nieuwenhze, Michael S.;  Brun, Yves, V;  Wright, Gerard D.
收藏  |  浏览/下载:31/0  |  提交时间:2020/07/03

Spin-based logic architectures provide nonvolatile data retention, near-zero leakage, and scalability, extending the technology roadmap beyond complementary metal-oxide-semiconductor logic(1-13). Architectures based on magnetic domain walls take advantage of the fast motion, high density, non-volatility and flexible design of domain walls to process and store information(1,3,14-16). Such schemes, however, rely on domain-wall manipulation and clocking using an external magnetic field, which limits their implementation in dense, large-scale chips. Here we demonstrate a method for performing all-electric logic operations and cascading using domain-wall racetracks. We exploit the chiral coupling between neighbouring magnetic domains induced by the interfacial Dzyaloshinskii-Moriya interaction(17-20), which promotes non-collinear spin alignment, to realize a domain-wall inverter, the essential basic building block in all implementations of Boolean logic. We then fabricate reconfigurable NAND and NOR logic gates, and perform operations with current-induced domain-wall motion. Finally, we cascade several NAND gates to build XOR and full adder gates, demonstrating electrical control of magnetic data and device interconnection in logic circuits. Our work provides a viable platform for scalable all-electric magnetic logic, paving the way for memory-in-logic applications.