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Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells 期刊论文
Science, 2020
作者:  Zhiwei Zhou;  Huabin He;  Kun Wang;  Xuyan Shi;  Yupeng Wang;  Ya Su;  Yao Wang;  Da Li;  Wang Liu;  Yongliang Zhang;  Lianjun Shen;  Weidong Han;  Lin Shen;  Jingjin Ding;  Feng Shao
收藏  |  浏览/下载:13/0  |  提交时间:2020/06/01
Integrating genomic features for non-invasive early lung cancer detection 期刊论文
NATURE, 2020, 580 (7802) : 245-+
作者:  Wang, Qinyang;  Wang, Yupeng;  Ding, Jingjin;  Wang, Chunhong;  Zhou, Xuehan;  Gao, Wenqing;  Huang, Huanwei;  Shao, Feng;  Liu, Zhibo
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03

Circulating tumour DNA in blood is analysed to identify genomic features that distinguish early-stage lung cancer patients from risk-matched controls, and these are integrated into a machine-learning method for blood-based lung cancer screening.


Radiologic screening of high-risk adults reduces lung-cancer-related mortality(1,2)  however, a small minority of eligible individuals undergo such screening in the United States(3,4). The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)(5), a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic. We also find that the majority of somatic mutations in the cell-free DNA (cfDNA) of patients with lung cancer and of risk-matched controls reflect clonal haematopoiesis and are non-recurrent. Compared with tumour-derived mutations, clonal haematopoiesis mutations occur on longer cfDNA fragments and lack mutational signatures that are associated with tobacco smoking. Integrating these findings with other molecular features, we develop and prospectively validate a machine-learning method termed '  lung cancer likelihood in plasma'  (Lung-CLiP), which can robustly discriminate early-stage lung cancer patients from risk-matched controls. This approach achieves performance similar to that of tumour-informed ctDNA detection and enables tuning of assay specificity in order to facilitate distinct clinical applications. Our findings establish the potential of cfDNA for lung cancer screening and highlight the importance of risk-matching cases and controls in cfDNA-based screening studies.


  
Collisional cooling of ultracold molecules 期刊论文
NATURE, 2020, 580 (7802) : 197-+
作者:  Wang, Qinyang;  Wang, Yupeng;  Ding, Jingjin;  Wang, Chunhong;  Zhou, Xuehan;  Gao, Wenqing;  Huang, Huanwei;  Shao, Feng;  Liu, Zhibo
收藏  |  浏览/下载:11/0  |  提交时间:2020/07/03

Since the original work on Bose-Einstein condensation(1,2), the use of quantum degenerate gases of atoms has enabled the quantum emulation of important systems in condensed matter and nuclear physics, as well as the study of many-body states that have no analogue in other fields of physics(3). Ultracold molecules in the micro- and nanokelvin regimes are expected to bring powerful capabilities to quantum emulation(4) and quantum computing(5), owing to their rich internal degrees of freedom compared to atoms, and to facilitate precision measurement and the study of quantum chemistry(6). Quantum gases of ultracold atoms can be created using collision-based cooling schemes such as evaporative cooling, but thermalization and collisional cooling have not yet been realized for ultracold molecules. Other techniques, such as the use of supersonic jets and cryogenic buffer gases, have reached temperatures limited to above 10 millikelvin(7,8). Here we show cooling of NaLi molecules to micro- and nanokelvin temperatures through collisions with ultracold Na atoms, with both molecules and atoms prepared in their stretched hyperfine spin states. We find a lower bound on the ratio of elastic to inelastic molecule-atom collisions that is greater than 50-large enough to support sustained collisional cooling. By employing two stages of evaporation, we increase the phase-space density of the molecules by a factor of 20, achieving temperatures as low as 220 nanokelvin. The favourable collisional properties of the Na-NaLi system could enable the creation of deeply quantum degenerate dipolar molecules and raises the possibility of using stretched spin states in the cooling of other molecules.


NaLi molecules are cooled to micro- and nanokelvin temperatures through collisions with ultracold Na atoms by using molecules and atoms in stretched hyperfine spin states and applying two evaporation stages.


  
Live-animal imaging of native haematopoietic stem and progenitor cells 期刊论文
NATURE, 2020, 578 (7794) : 278-+
作者:  Gerstung, Moritz;  Jolly, Clemency;  Leshchiner, Ignaty;  Dentro, Stefan C.;  Gonzalez, Santiago;  Rosebrock, Daniel;  Mitchell, Thomas J.;  Rubanova, Yulia;  Anur, Pavana;  Yu, Kaixian;  Tarabichi, Maxime;  Deshwar, Amit;  Wintersinger, Jeff;  Kleinheinz, Kortine;  Vazquez-Garcia, Ignacio;  Haase, Kerstin;  Jerman, Lara;  Sengupta, Subhajit;  Macintyre, Geoff;  Malikic, Salem;  Donmez, Nilgun;  Livitz, Dimitri G.;  Cmero, Marek;  Demeulemeester, Jonas;  Schumacher, Steven;  Fan, Yu;  Yao, Xiaotong;  Lee, Juhee;  Schlesner, Matthias;  Boutros, Paul C.;  Bowtell, David D.;  Zhu, Hongtu;  Getz, Gad;  Imielinski, Marcin;  Beroukhim, Rameen;  Sahinalp, S. Cenk;  Ji, Yuan;  Peifer, Martin;  Markowetz, Florian;  Mustonen, Ville;  Yuan, Ke;  Wang, Wenyi;  Morris, Quaid D.;  Spellman, Paul T.;  Wedge, David C.;  Van Loo, Peter;  Deshwar, Amit G.;  Adams, David J.;  Campbell, Peter J.;  Cao, Shaolong;  Christie, Elizabeth L.;  Cun, Yupeng;  Dawson, Kevin J.;  Drews, Ruben M.;  Eils, Roland;  Fittall, Matthew;  Garsed, Dale W.;  Ha, Gavin;  Lee-Six, Henry;  Martincorena, Inigo;  Oesper, Layla;  Peto, Myron;  Raphael, Benjamin J.;  Salcedo, Adriana;  Shi, Ruian;  Shin, Seung Jun;  Spiro, Oliver;  Stein, Lincoln D.;  Vembu, Shankar;  Wheeler, David A.;  Yang, Tsun-Po
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03

The biology of haematopoietic stem cells (HSCs) has predominantly been studied under transplantation conditions(1,2). It has been particularly challenging to study dynamic HSC behaviour, given that the visualization of HSCs in the native niche in live animals has not, to our knowledge, been achieved. Here we describe a dual genetic strategy in mice that restricts reporter labelling to a subset of the most quiescent long-term HSCs (LT-HSCs) and that is compatible with current intravital imaging approaches in the calvarial bone marrow(3-5). We show that this subset of LT-HSCs resides close to both sinusoidal blood vessels and the endosteal surface. By contrast, multipotent progenitor cells (MPPs) show greater variation in distance from the endosteum and are more likely to be associated with transition zone vessels. LT-HSCs are not found in bone marrow niches with the deepest hypoxia and instead are found in hypoxic environments similar to those of MPPs. In vivo time-lapse imaging revealed that LT-HSCs at steady-state show limited motility. Activated LT-HSCs show heterogeneous responses, with some cells becoming highly motile and a fraction of HSCs expanding clonally within spatially restricted domains. These domains have defined characteristics, as HSC expansion is found almost exclusively in a subset of bone marrow cavities with bone-remodelling activity. By contrast, cavities with low bone-resorbing activity do not harbour expanding HSCs. These findings point to previously unknown heterogeneity within the bone marrow microenvironment, imposed by the stages of bone turnover. Our approach enables the direct visualization of HSC behaviours and dissection of heterogeneity in HSC niches.


A dual genetic strategy enables the labelling and in vivo imaging of native long-term haematopoietic stem cells in the mouse calvarial bone marrow.


  
天基太阳光谱绝对测量辐射基准建立及向它星传递链路研究 项目
项目编号:41474161; 经费:1000000(CNY); 起止日期:2015 / dc_date_end
项目负责人:  王玉鹏
收藏  |  浏览/下载:6/0  |  提交时间:2019/04/11