GSTDTAP

浏览/检索结果: 共69条,第1-10条 帮助

限定条件    
已选(0)清除 条数/页:   排序方式:
Sea-ice loss amplifies summertime decadal CO(2)increase in the western Arctic Ocean 期刊论文
NATURE CLIMATE CHANGE, 2020, 10 (7) : 678-+
作者:  Ouyang, Zhangxian;  Qi, Di;  Chen, Liqi;  Takahashi, Taro;  Zhong, Wenli;  DeGrandpre, Michael D.;  Chen, Baoshan;  Gao, Zhongyong;  Nishino, Shigeto;  Murata, Akihiko;  Sun, Heng;  Robbins, Lisa L.;  Jin, Meibing;  Cai, Wei-Jun
收藏  |  浏览/下载:15/0  |  提交时间:2020/06/22
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.


  
HBO1 is required for the maintenance of leukaemia stem cells 期刊论文
NATURE, 2020, 577 (7789) : 266-+
作者:  MacPherson, Laura;  Anokye, Juliana;  Yeung, Miriam M.;  Lam, Enid Y. N.;  Chan, Yih-Chih;  Weng, Chen-Fang;  Yeh, Paul;  Knezevic, Kathy;  Butler, Miriam S.;  Hoegl, Annabelle;  Chan, Kah-Lok;  Burr, Marian L.;  Gearing, Linden J.;  Willson, Tracy;  Liu, Joy;  Choi, Jarny;  Yang, Yuqing;  Bilardi, Rebecca A.;  Falk, Hendrik;  Nghi Nguyen;  Stupple, Paul A.;  Peat, Thomas S.;  Zhang, Ming;  de Silva, Melanie;  Carrasco-Pozo, Catalina;  Avery, Vicky M.;  Khoo, Poh Sim;  Dolezal, Olan;  Dennis, Matthew L.;  Nuttall, Stewart;  Surjadi, Regina;  Newman, Janet;  Ren, Bin;  Leaver, David J.;  Sun, Yuxin;  Baell, Jonathan B.;  Dovey, Oliver;  Vassiliou, George S.;  Grebien, Florian;  Dawson, Sarah-Jane;  Street, Ian P.;  Monahan, Brendon J.;  Burns, Christopher J.;  Choudhary, Chunaram;  Blewitt, Marnie E.;  Voss, Anne K.;  Thomas, Tim;  Dawson, Mark A.
收藏  |  浏览/下载:16/0  |  提交时间:2020/07/03

Acute myeloid leukaemia (AML) is a heterogeneous disease characterized by transcriptional dysregulation that results in a block in differentiation and increased malignant self-renewal. Various epigenetic therapies aimed at reversing these hallmarks of AML have progressed into clinical trials, but most show only modest efficacy owing to an inability to effectively eradicate leukaemia stem cells (LSCs)(1). Here, to specifically identify novel dependencies in LSCs, we screened a bespoke library of small hairpin RNAs that target chromatin regulators in a unique ex vivo mouse model of LSCs. We identify the MYST acetyltransferase HBO1 (also known as KAT7 or MYST2) and several known members of the HBO1 protein complex as critical regulators of LSC maintenance. Using CRISPR domain screening and quantitative mass spectrometry, we identified the histone acetyltransferase domain of HBO1 as being essential in the acetylation of histone H3 at K14. H3 acetylated at K14 (H3K14ac) facilitates the processivity of RNA polymerase II to maintain the high expression of key genes (including Hoxa9 and Hoxa10) that help to sustain the functional properties of LSCs. To leverage this dependency therapeutically, we developed a highly potent small-molecule inhibitor of HBO1 and demonstrate its mode of activity as a competitive analogue of acetyl-CoA. Inhibition of HBO1 phenocopied our genetic data and showed efficacy in a broad range of human cell lines and primary AML cells from patients. These biological, structural and chemical insights into a therapeutic target in AML will enable the clinical translation of these findings.


  
Environmental reservoir dynamics predict global infection patterns and population impacts for the fungal disease white-nose syndrome 期刊论文
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 117 (13) : 7255-7262
作者:  Hoyt, Joseph R.;  Langwig, Kate E.;  Sun, Keping;  Parise, Katy L.;  Li, Aoqiang;  Wang, Yujuan;  Huang, Xiaobin;  Worledge, Lisa;  Miller, Helen;  White, J. Paul;  Kaarakka, Heather M.;  Redell, Jennifer A.;  Gorfol, Tamas;  Boldogh, Sandor Andras;  Fukui, Dai;  Sakuyama, Muneki;  Yachimori, Syuuji;  Sato, Akiyoshi;  Dalannast, Munkhnast;  Jargalsaikhan, Ariunbold;  Batbayar, Nyambayar;  Yovel, Yossi;  Amichai, Eran;  Natradze, Ioseb;  Frick, Winifred F.;  Foster, Jeffrey T.;  Feng, Jiang;  Kilpatrick, A. Marm
收藏  |  浏览/下载:14/0  |  提交时间:2020/05/13
environmental pathogen reservoir  global disease dynamics  white-nose syndrome  Pseudogymnoascus destructans  
Probing Effective Wetting in Subsurface Systems 期刊论文
GEOPHYSICAL RESEARCH LETTERS, 2020, 47 (5)
作者:  Sun, Chenhao;  McClure, James E.;  Mostaghimi, Peyman;  Herring, Anna L.;  Berg, Steffen;  Armstrong, Ryan T.
收藏  |  浏览/下载:4/0  |  提交时间:2020/07/02
An unexpected catalyst dominates formation and radiative forcing of regional haze 期刊论文
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 117 (8) : 3960-3966
作者:  Zhang, Fang;  Wang, Yuan;  Peng, Jianfei;  Chen, Lu;  Sun, Yele;  Duan, Lian;  Ge, Xinlei;  Li, Yixin;  Zhao, Jiayun;  Liu, Chao;  Zhang, Xiaochun;  Zhang, Gen;  Pan, Yuepeng;  Wang, Yuesi;  Zhang, Annie L.;  Ji, Yuemeng;  Wang, Gehui;  Hu, Min;  Molina, Mario J.;  Zhang, Renyi
收藏  |  浏览/下载:16/0  |  提交时间:2020/05/13
black carbon  air pollution  climate  multiphase chemistry  haze  
Using yeast to sustainably remediate and extract heavy metals from waste waters 期刊论文
NATURE SUSTAINABILITY, 2020, 3 (4) : 303-+
作者:  Sun, George L.;  Reynolds, Erin. E.;  Belcher, Angela M.
收藏  |  浏览/下载:3/0  |  提交时间:2020/05/13
Cluster Observations on Time-of-Flight Effect of Oxygen Ions in Magnetotail Reconnection Exhaust Region 期刊论文
GEOPHYSICAL RESEARCH LETTERS, 2020, 47 (3)
作者:  Wu, T.;  Fu, S. Y.;  Xie, L.;  Zong, Q-G;  Zhou, X. Z.;  Yue, C.;  Sun, W. J.;  Pu, Z. Y.;  Xiong, Y.;  Zhao, S. J.;  Zhang, H.;  Yu, F. B.
收藏  |  浏览/下载:14/0  |  提交时间:2020/07/02
A mycobacterial ABC transporter mediates the uptake of hydrophilic compounds 期刊论文
NATURE, 2020, 580 (7803) : 409-+
作者:  Al-Shayeb, Basem;  Sachdeva, Rohan;  Chen, Lin-Xing;  Ward, Fred;  Munk, Patrick;  Devoto, Audra;  Castelle, Cindy J.;  Olm, Matthew R.;  Bouma-Gregson, Keith;  Amano, Yuki;  He, Christine;  Meheust, Raphael;  Brooks, Brandon;  Thomas, Alex;  Levy, Adi;  Matheus-Carnevali, Paula;  Sun, Christine;  Goltsman, Daniela S. A.;  Borton, Mikayla A.;  Sharrar, Allison;  Jaffe, Alexander L.;  Nelson, Tara C.;  Kantor, Rose;  Keren, Ray;  Lane, Katherine R.;  Farag, Ibrahim F.;  Lei, Shufei;  Finstad, Kari;  Amundson, Ronald;  Anantharaman, Karthik;  Zhou, Jinglie;  Probst, Alexander J.;  Power, Mary E.;  Tringe, Susannah G.;  Li, Wen-Jun;  Wrighton, Kelly;  Harrison, Sue;  Morowitz, Michael;  Relman, David A.;  Doudna, Jennifer A.;  Lehours, Anne-Catherine;  Warren, Lesley;  Cate, Jamie H. D.;  Santini, Joanne M.;  Banfield, Jillian F.
收藏  |  浏览/下载:34/0  |  提交时间:2020/07/03

Mycobacterium tuberculosis (Mtb) is an obligate human pathogen and the causative agent of tuberculosis(1-3). Although Mtb can synthesize vitamin B-12 (cobalamin) de novo, uptake of cobalamin has been linked to pathogenesis of tuberculosis2. Mtb does not encode any characterized cobalamin transporter(4-6)  however, the gene rv1819c was found to be essential for uptake of cobalamin(1). This result is difficult to reconcile with the original annotation of Rv1819c as a protein implicated in the transport of antimicrobial peptides such as bleomycin(7). In addition, uptake of cobalamin seems inconsistent with the amino acid sequence, which suggests that Rv1819c has a bacterial ATP-binding cassette (ABC)-exporter fold1. Here, we present structures of Rv1819c, which reveal that the protein indeed contains the ABC-exporter fold, as well as a large water-filled cavity of about 7,700 angstrom(3), which enables the protein to transport the unrelated hydrophilic compounds bleomycin and cobalamin. On the basis of these structures, we propose that Rv1819c is a multi-solute transporter for hydrophilic molecules, analogous to the multidrug exporters of the ABC transporter family, which pump out structurally diverse hydrophobic compounds from cells(8-11).


  
Microbiota-targeted maternal antibodies protect neonates from enteric infection 期刊论文
NATURE, 2020, 577 (7791) : 543-+
作者:  Zheng, Wen;  Zhao, Wenjing;  Wu, Meng;  Song, Xinyang;  Caro, Florence;  Sun, Ximei;  Gazzaniga, Francesca;  Stefanetti, Giuseppe;  Oh, Sungwhan;  Mekalanos, John J.;  Kasper, Dennis L.
收藏  |  浏览/下载:6/0  |  提交时间:2020/07/03

Although maternal antibodies protect newborn babies from infection(1,2), little is known about how protective antibodies are induced without prior pathogen exposure. Here we show that neonatal mice that lack the capacity to produce IgG are protected from infection with the enteric pathogen enterotoxigenic Escherichia coli by maternal natural IgG antibodies against the maternal microbiota when antibodies are delivered either across the placenta or through breast milk. By challenging pups that were fostered by either maternal antibody-sufficient or antibody-deficient dams, we found that IgG derived from breast milk was crucial for protection against mucosal disease induced by enterotoxigenic E. coli. IgG also provides protection against systemic infection by E. coli. Pups used the neonatal Fc receptor to transfer IgG from milk into serum. The maternal commensal microbiota can induce antibodies that recognize antigens expressed by enterotoxigenic E. coli and other Enterobacteriaceae species. Induction of maternal antibodies against a commensal Pantoea species confers protection against enterotoxigenic E. coli in pups. This role of the microbiota in eliciting protective antibodies to a specific neonatal pathogen represents an important host defence mechanism against infection in neonates.


Neonatal mice are protected against infection with the enteric pathogen enterotoxigenic Escherichia coli by maternally derived natural antibodies as well as by maternal commensal microbiota that induce antibodies that recognize antigens expressed by Enterobacteriaceae.