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Validation of Aura-OMI QA4ECV NO2 climate data records with ground-based DOAS networks: the role of measurement and comparison uncertainties 期刊论文
ATMOSPHERIC CHEMISTRY AND PHYSICS, 2020, 20 (13) : 8017-8045
作者:  Compernolle, Steven;  Verhoelst, Tijl;  Pinardi, Gaia;  Granville, Jose;  Hubert, Daan;  Keppens, Arno;  Niemeijer, Sander;  Rino, Bruno;  Bais, Alkis;  Beirle, Steffen;  Boersma, Folkert;  Burrows, John P.;  De Smedt, Isabelle;  Eskes, Henk;  Goutail, Florence;  Hendrick, Francois;  Lorente, Alba;  Pazmino, Andrea;  Piters, Ankie;  Peters, Enno;  Pommereau, Jean-Pierre;  Remmers, Julia;  Richter, Andreas;  van Geffen, Jos;  Van Roozendael, Michel;  Wagner, Thomas;  Lambert, Jean-Christopher
收藏  |  浏览/下载:10/0  |  提交时间:2020/08/18
Southern Ocean carbon sink enhanced by sea-ice feedbacks at the Antarctic Cold Reversal 期刊论文
NATURE GEOSCIENCE, 2020, 13 (7) : 489-+
作者:  Fogwill, C. J.;  Turney, C. S. M.;  Menviel, L.;  Baker, A.;  Weber, M. E.;  Ellis, B.;  Thomas, Z. A.;  Golledge, N. R.;  Etheridge, D.;  Rubino, M.;  Thornton, D. P.;  van Ommen, T. D.;  Moy, A. D.;  Curran, M. A. J.;  Davies, S.;  Bird, M., I;  Munksgaard, N. C.;  Rootes, C. M.;  Millman, H.;  Vohra, J.;  Rivera, A.;  Mackintosh, A.;  Pike, J.;  Hall, I. R.;  Bagshaw, E. A.;  Rainsley, E.;  Bronk-Ramsey, C.;  Montenari, M.;  Cage, A. G.;  Harris, M. R. P.;  Jones, R.;  Power, A.;  Love, J.;  Young, J.;  Weyrich, L. S.;  Cooper, A.
收藏  |  浏览/下载:14/0  |  提交时间:2020/06/29
Geometry and evolution of the ecological niche in plant-associated microbes 期刊论文
NATURE COMMUNICATIONS, 2020, 11 (1)
作者:  Chaloner, Thomas M.;  Gurr, Sarah J.;  Bebber, Daniel P.
收藏  |  浏览/下载:7/0  |  提交时间:2020/06/16
A Galactic-scale gas wave in the solar neighbourhood 期刊论文
NATURE, 2020, 578 (7794) : 237-+
作者:  Alves, Joao;  Zucker, Catherine;  Goodman, Alyssa A.;  Speagle, Joshua S.;  Meingast, Stefan;  Robitaille, Thomas;  Finkbeiner, Douglas P.;  Schlafly, Edward F.;  Green, Gregory M.
收藏  |  浏览/下载:14/0  |  提交时间:2020/07/03

The three-dimensional structure of all cloud complexes in the solar neighbourhood is revealed, showing a narrow and coherent 2.7-kpc arrangement of dense gas, in disagreement with the Gould Belt model.


For the past 150 years, the prevailing view of the local interstellar medium has been based on a peculiarity known as the Gould Belt(1-4), an expanding ring of young stars, gas and dust, tilted about 20 degrees to the Galactic plane. However, the physical relationship between local gas clouds has remained unknown because the accuracy in distance measurements to such clouds is of the same order as, or larger than, their sizes(5-7). With the advent of large photometric surveys(8) and the astrometric survey(9), this situation has changed(10). Here we reveal the three-dimensional structure of all local cloud complexes. We find a narrow and coherent 2.7-kiloparsec arrangement of dense gas in the solar neighbourhood that contains many of the clouds thought to be associated with the Gould Belt. This finding is inconsistent with the notion that these clouds are part of a ring, bringing the Gould Belt model into question. The structure comprises the majority of nearby star-forming regions, has an aspect ratio of about 1:20 and contains about three million solar masses of gas. Remarkably, this structure appears to be undulating, and its three-dimensional shape is well described by a damped sinusoidal wave on the plane of the Milky Way with an average period of about 2 kiloparsecs and a maximum amplitude of about 160 parsecs.


  
Role of Cyclone "Ockhi" in the re-distribution of aerosols and its impact on the precipitation over the Arabian Sea 期刊论文
ATMOSPHERIC RESEARCH, 2020, 235
作者:  Nair, Arun;  Das, Siddarth S.;  Thomas, Abin;  Sarangi, Chandan;  Kanawade, Vijay P.
收藏  |  浏览/下载:7/0  |  提交时间:2020/07/02
Ockhi  Arabian Sea  Aerosol-cloud interactions  Cyclogenesis  
Metabolic heterogeneity confers differences in melanoma metastatic potential 期刊论文
NATURE, 2020, 577 (7788) : 115-+
作者:  Tasdogan, Alpaslan;  Faubert, Brandon;  Ramesh, Vijayashree;  Ubellacker, Jessalyn M.;  Shen, Bo;  Solmonson, Ashley;  Murphy, Malea M.;  Gu, Zhimin;  Gu, Wen;  Martin, Misty;  Kasitinon, Stacy Y.;  Vandergriff, Travis;  Mathews, Thomas P.;  Zhao, Zhiyu;  Schadendorf, Dirk;  DeBerardinis, Ralph J.;  Morrison, Sean J.
收藏  |  浏览/下载:14/0  |  提交时间:2020/07/03

Metastasis requires cancer cells to undergo metabolic changes that are poorly understood(1-3). Here we show that metabolic differences among melanoma cells confer differences in metastatic potential as a result of differences in the function of the MCT1 transporter. In vivo isotope tracing analysis in patient-derived xenografts revealed differences in nutrient handling between efficiently and inefficiently metastasizing melanomas, with circulating lactate being a more prominent source of tumour lactate in efficient metastasizers. Efficient metastasizers had higher levels of MCT1, and inhibition of MCT1 reduced lactate uptake. MCT1 inhibition had little effect on the growth of primary subcutaneous tumours, but resulted in depletion of circulating melanoma cells and reduced the metastatic disease burden in patient-derived xenografts and in mouse melanomas. In addition, inhibition of MCT1 suppressed the oxidative pentose phosphate pathway and increased levels of reactive oxygen species. Antioxidants blocked the effects of MCT1 inhibition on metastasis. MCT1(high) and MCT1(-/low) cells from the same melanomas had similar capacities to form subcutaneous tumours, but MCT1(high) cells formed more metastases after intravenous injection. Metabolic differences among cancer cells thus confer differences in metastatic potential as metastasizing cells depend on MCT1 to manage oxidative stress.


  
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:17/0  |  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.


  
The acidity of atmospheric particles and clouds 期刊论文
ATMOSPHERIC CHEMISTRY AND PHYSICS, 2020, 20 (8) : 4809-4888
作者:  Pye, Havala O. T.;  Nenes, Athanasios;  Alexander, Becky;  Ault, Andrew P.;  Barth, Mary C.;  Clegg, Simon L.;  Collett, Jeffrey L., Jr.;  Fahey, Kathleen M.;  Hennigan, Christopher J.;  Herrmann, Hartmut;  Kanakidou, Maria;  Kelly, James T.;  Ku, I-Ting;  McNeill, V. Faye;  Riemer, Nicole;  Schaefer, Thomas;  Shi, Guoliang;  Tilgner, Andreas;  Walker, John T.;  Wang, Tao;  Weber, Rodney;  Xing, Jia;  Zaveri, Rahul A.;  Zuend, Andreas
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/02
Structural transitions in influenza haemagglutinin at membrane fusion pH 期刊论文
NATURE, 2020, 583 (7814) : 150-+
作者:  Wei, Kevin;  Korsunsky, Ilya;  Marshall, Jennifer L.;  Gao, Anqi;  Watts, Gerald F. M.;  Major, Triin;  Croft, Adam P.;  Watts, Jordan;  Blazar, Philip E.;  Lange, Jeffrey K.;  Thornhill, Thomas S.;  Filer, Andrew;  Raza, Karim;  Donlin, Laura T.;  Siebel, Christian W.
收藏  |  浏览/下载:20/0  |  提交时间:2020/07/03

Cryo-electron microscopy studies of the influenza haemagglutinin glycoprotein at the low pH of host endosomes reveals structural intermediates, offering a dynamic view of how the protein mediates membrane fusion.


Infection by enveloped viruses involves fusion of their lipid envelopes with cellular membranes to release the viral genome into cells. For HIV, Ebola, influenza and numerous other viruses, envelope glycoproteins bind the infecting virion to cell-surface receptors and mediate membrane fusion. In the case of influenza, the receptor-binding glycoprotein is the haemagglutinin (HA), and following receptor-mediated uptake of the bound virus by endocytosis(1), it is the HA that mediates fusion of the virus envelope with the membrane of the endosome(2). Each subunit of the trimeric HA consists of two disulfide-linked polypeptides, HA1 and HA2. The larger, virus-membrane-distal, HA1 mediates receptor binding  the smaller, membrane-proximal, HA2 anchors HA in the envelope and contains the fusion peptide, a region that is directly involved in membrane interaction(3). The low pH of endosomes activates fusion by facilitating irreversible conformational changes in the glycoprotein. The structures of the initial HA at neutral pH and the final HA at fusion pH have been investigated by electron microscopy(4,5) and X-ray crystallography(6-8). Here, to further study the process of fusion, we incubate HA for different times at pH 5.0 and directly image structural changes using single-particle cryo-electron microscopy. We describe three distinct, previously undescribed forms of HA, most notably a 150 angstrom-long triple-helical coil of HA2, which may bridge between the viral and endosomal membranes. Comparison of these structures reveals concerted conformational rearrangements through which the HA mediates membrane fusion.


  
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