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Persistence of soil organic carbon caused by functional complexity 期刊论文
NATURE GEOSCIENCE, 2020
作者:  Lehmann, Johannes;  Hansel, Colleen M.;  Kaiser, Christina;  Kleber, Markus;  Maher, Kate;  Manzoni, Stefano;  Nunan, Naoise;  Reichstein, Markus;  Schimel, Joshua P.;  Torn, Margaret S.;  Wieder, William R.;  Koegel-Knabner, Ingrid
收藏  |  浏览/下载:12/0  |  提交时间:2020/08/09
Carbon loss from northern circumpolar permafrost soils amplified by rhizosphere priming 期刊论文
NATURE GEOSCIENCE, 2020
作者:  Keuper, Frida;  Wild, Birgit;  Kummu, Matti;  Beer, Christian;  Blume-Werry, Gesche;  Fontaine, Sebastien;  Gavazov, Konstantin;  Gentsch, Norman;  Guggenberger, Georg;  Hugelius, Gustaf;  Jalava, Mika;  Koven, Charles;  Krab, Eveline J.;  Kuhry, Peter;  Monteux, Sylvain;  Richter, Andreas;  Shahzad, Tanvir;  Weedon, James T.;  Dorrepaal, Ellen
收藏  |  浏览/下载:12/0  |  提交时间:2020/08/09
Widespread biomass burning smoke throughout the remote troposphere 期刊论文
NATURE GEOSCIENCE, 2020, 13 (6) : 422-+
作者:  Schill, G. P.;  Froyd, K. D.;  Bian, H.;  Kupc, A.;  Williamson, C.;  Brock, C. A.;  Ray, E.;  Hornbrook, R. S.;  Hills, A. J.;  Apel, E. C.;  Chin, M.;  Colarco, P. R.;  Murphy, D. M.
收藏  |  浏览/下载:6/0  |  提交时间:2020/06/09
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.


  
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.


  
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.


  
Cellular locomotion using environmental topography 期刊论文
NATURE, 2020
作者:  Fernandez, Diego Carlos;  Komal, Ruchi;  Langel, Jennifer;  Ma, Jun;  Duy, Phan Q.;  Penzo, Mario A.;  Zhao, Haiqing;  Hattar, Samer
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03

Within three-dimensional environments, leukocytes can migrate even in the complete absence of adhesive forces using the topographical features of the substrate to propel themselves.


Eukaryotic cells migrate by coupling the intracellular force of the actin cytoskeleton to the environment. While force coupling is usually mediated by transmembrane adhesion receptors, especially those of the integrin family, amoeboid cells such as leukocytes can migrate extremely fast despite very low adhesive forces(1). Here we show that leukocytes cannot only migrate under low adhesion but can also transmit forces in the complete absence of transmembrane force coupling. When confined within three-dimensional environments, they use the topographical features of the substrate to propel themselves. Here the retrograde flow of the actin cytoskeleton follows the texture of the substrate, creating retrograde shear forces that are sufficient to drive the cell body forwards. Notably, adhesion-dependent and adhesion-independent migration are not mutually exclusive, but rather are variants of the same principle of coupling retrograde actin flow to the environment and thus can potentially operate interchangeably and simultaneously. As adhesion-free migration is independent of the chemical composition of the environment, it renders cells completely autonomous in their locomotive behaviour.


  
TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9 期刊论文
NATURE, 2020, 581 (7808) : 316-+
作者:  Kokail, C.;  Maier, C.;  van Bijnen, R.;  Brydges, T.;  Joshi, M. K.;  Jurcevic, P.;  Muschik, C. A.;  Silvi, P.;  Blatt, R.;  Roos, C. F.;  Zoller, P.
收藏  |  浏览/下载:27/0  |  提交时间:2020/07/03

The interaction between TASL and SLC15A4 links endolysosomal Toll-like receptors to the transcription factor IRF5, providing a mechanistic explanation for the involvement of the complex in systemic lupus erythematosus.


Toll-like receptors (TLRs) have a crucial role in the recognition of pathogens and initiation of immune responses(1-3). Here we show that a previously uncharacterized protein encoded by CXorf21-a gene that is associated with systemic lupus erythematosus(4,5)-interacts with the endolysosomal transporter SLC15A4, an essential but poorly understood component of the endolysosomal TLR machinery also linked to autoimmune disease(4,6-9). Loss of this type-I-interferon-inducible protein, which we refer to as '  TLR adaptor interacting with SLC15A4 on the lysosome'  (TASL), abrogated responses to endolysosomal TLR agonists in both primary and transformed human immune cells. Deletion of SLC15A4 or TASL specifically impaired the activation of the IRF pathway without affecting NF-kappa B and MAPK signalling, which indicates that ligand recognition and TLR engagement in the endolysosome occurred normally. Extensive mutagenesis of TASL demonstrated that its localization and function relies on the interaction with SLC15A4. TASL contains a conserved pLxIS motif (in which p denotes a hydrophilic residue and x denotes any residue) that mediates the recruitment and activation of IRF5. This finding shows that TASL is an innate immune adaptor for TLR7, TLR8 and TLR9 signalling, revealing a clear mechanistic analogy with the IRF3 adaptors STING, MAVS and TRIF10,11. The identification of TASL as the component that links endolysosomal TLRs to the IRF5 transcription factor via SLC15A4 provides a mechanistic explanation for the involvement of these proteins in systemic lupus erythematosus(12-14).


  
Variability in the analysis of a single neuroimaging dataset by many teams 期刊论文
NATURE, 2020
作者:  Liu, Jifeng;  Soria, Roberto;  Zheng, Zheng;  Zhang, Haotong;  Lu, Youjun;  Wang, Song;  Yuan, Hailong
收藏  |  浏览/下载:22/0  |  提交时间:2020/07/03

Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.


The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.


  
Direct-bandgap emission from hexagonal Ge and SiGe alloys 期刊论文
NATURE, 2020, 580 (7802) : 205-+
作者:  Meiners, Thorsten;  Frolov, Timofey;  Rudd, Robert E.;  Dehm, Gerhard;  Liebscher, Christian H.
收藏  |  浏览/下载:28/0  |  提交时间:2020/07/03

Silicon crystallized in the usual cubic (diamond) lattice structure has dominated the electronics industry for more than half a century. However, cubic silicon (Si), germanium (Ge) and SiGe alloys are all indirect-bandgap semiconductors that cannot emit light efficiently. The goal(1) of achieving efficient light emission from group-IV materials in silicon technology has been elusive for decades(2-6). Here we demonstrate efficient light emission from direct-bandgap hexagonal Ge and SiGe alloys. We measure a sub-nanosecond, temperature-insensitive radiative recombination lifetime and observe an emission yield similar to that of direct-bandgap group-III-V semiconductors. Moreover, we demonstrate that, by controlling the composition of the hexagonal SiGe alloy, the emission wavelength can be continuously tuned over a broad range, while preserving the direct bandgap. Our experimental findings are in excellent quantitative agreement with ab initio theory. Hexagonal SiGe embodies an ideal material system in which to combine electronic and optoelectronic functionalities on a single chip, opening the way towards integrated device concepts and information-processing technologies.


A hexagonal (rather than cubic) alloy of silicon and germanium that has a direct (rather than indirect) bandgap emits light efficiently across a range of wavelengths, enabling electronic and optoelectronic functionalities to be combined on a single chip.