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Revealing enigmatic mucus structures in the deep sea using DeepPIV 期刊论文
NATURE, 2020, 583 (7814) : 78-+
作者:  Nguyen, Ngoc Uyen Nhi;  Canseco, Diana C.;  Xiao, Feng;  Nakada, Yuji;  Li, Shujuan;  Lam, Nicholas T.;  Muralidhar, Shalini A.;  Savla, Jainy J.;  Hill, Joseph A.;  Le, Victor;  Zidan, Kareem A.;  El-Feky, Hamed W.;  Wang, Zhaoning;  Ahmed, Mahmoud Salama;  Hubbi, Maimon E.;  Menendez-Montes, Ivan
收藏  |  浏览/下载:50/0  |  提交时间:2020/06/09

Advanced deep-sea imaging tools yield insights into the structure and function of mucus filtration houses built by midwater giant larvaceans.


Many animals build complex structures to aid in their survival, but very few are built exclusively from materials that animals create (1,2). In the midwaters of the ocean, mucoid structures are readily secreted by numerous animals, and serve many vital functions(3,4). However, little is known about these mucoid structures owing to the challenges of observing them in the deep sea. Among these mucoid forms, the '  houses'  of larvaceans are marvels of nature(5), and in the ocean twilight zone giant larvaceans secrete and build mucus filtering structures that can reach diameters of more than 1 m(6). Here we describe in situ laser-imaging technology(7) that reconstructs three-dimensional models of mucus forms. The models provide high-resolution views of giant larvacean houses and elucidate the role that house structure has in food capture and predator avoidance. Now that tools exist to study mucus structures found throughout the ocean, we can shed light on some of nature'  s most complex forms.


  
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:55/0  |  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.


  
Epigenetic therapy inhibits metastases by disrupting premetastatic niches 期刊论文
NATURE, 2020, 579 (7798) : 284-+
作者:  Mehta, Vedanta;  Pang, Kar-Lai;  Rozbesky, Daniel;  Nather, Katrin;  Keen, Adam;  Lachowski, Dariusz;  Kong, Youxin;  Karia, Dimple;  Ameismeier, Michael;  Huang, Jianhua;  Fang, Yun;  del Rio Hernandez, Armando;  Reader, John S.;  Jones, E. Yvonne;  Tzima, Ellie
收藏  |  浏览/下载:25/0  |  提交时间:2020/07/03

Cancer recurrence after surgery remains an unresolved clinical problem(1-3). Myeloid cells derived from bone marrow contribute to the formation of the premetastatic microenvironment, which is required for disseminating tumour cells to engraft distant sites(4-6). There are currently no effective interventions that prevent the formation of the premetastatic microenvironment(6,7). Here we show that, after surgical removal of primary lung, breast and oesophageal cancers, low-dose adjuvant epigenetic therapy disrupts the premetastatic microenvironment and inhibits both the formation and growth of lung metastases through its selective effect on myeloid-derived suppressor cells (MDSCs). In mouse models of pulmonary metastases, MDSCs are key factors in the formation of the premetastatic microenvironment after resection of primary tumours. Adjuvant epigenetic therapy that uses low-dose DNA methyltransferase and histone deacetylase inhibitors, 5-azacytidine and entinostat, disrupts the premetastatic niche by inhibiting the trafficking of MDSCs through the downregulation of CCR2 and CXCR2, and by promoting MDSC differentiation into a more-interstitial macrophage-like phenotype. A decreased accumulation of MDSCs in the premetastatic lung produces longer periods of disease-free survival and increased overall survival, compared with chemotherapy. Our data demonstrate that, even after removal of the primary tumour, MDSCs contribute to the development of premetastatic niches and settlement of residual tumour cells. A combination of low-dose adjuvant epigenetic modifiers that disrupts this premetastatic microenvironment and inhibits metastases may permit an adjuvant approach to cancer therapy.


  
Persistence of a keystone microhabitat in boreal forests: Cavities of Eurasian Three-toed Woodpeckers (Picoides tridactylus) 期刊论文
FOREST ECOLOGY AND MANAGEMENT, 2019, 450
作者:  Hardenbol, Alwin A.;  Pakkala, Timo;  Kouki, Jari
收藏  |  浏览/下载:16/0  |  提交时间:2019/11/27
Cavity survival  Survival models  Three-toed woodpecker  Tree cavity  Tree-related microhabitats  Woodpecker cavity  
The diversity of population responses to environmental change 期刊论文
ECOLOGY LETTERS, 2019, 22 (2) : 342-353
作者:  Colchero, Fernando;  39;donnell, Colin
收藏  |  浏览/下载:7/0  |  提交时间:2019/04/09
Age-structured population models  Bayesian inference  fecundity  mortality  survival  
Signals of large scale climate drivers, hatchery enhancement, and marine factors in Yukon River Chinook salmon survival revealed with a Bayesian life history model 期刊论文
GLOBAL CHANGE BIOLOGY, 2018, 24 (9) : 4399-4416
作者:  Cunningham, Curry J.;  Westley, Peter A. H.;  Adkison, Milo D.
收藏  |  浏览/下载:21/0  |  提交时间:2019/04/09
Bayesian estimation  Chinook salmon conservation  climate change  environmental regulation of survival  life cycle models  marine and freshwater mortality  salmon assessment  Yukon River  
Limited validation of forecasted northward range shift in ten European tree species from a common garden experiment 期刊论文
FOREST ECOLOGY AND MANAGEMENT, 2018, 410: 144-156
作者:  Merlin, Morgane;  Duputie, Anne;  Chuine, Isabelle
收藏  |  浏览/下载:10/0  |  提交时间:2019/04/09
Climate change  Growth  Range shift  Recruitment  Seedlings  Species Distribution Models (SDM)  Survival  
Survival functions for boreal tree species in northwestern North America 期刊论文
FOREST ECOLOGY AND MANAGEMENT, 2017, 402
作者:  Cortini, Francesco;  Comeau, Philip G.;  Strimbu, Vlad C.;  Hogg, E. H. (Ted);  Bokalo, Mike;  Huang, Shongming
收藏  |  浏览/下载:11/0  |  提交时间:2019/04/09
Tree survival  Mortality  Logistic models  Estimates of competition  Climate variables  
Varying demographic impacts of different fisheries on three Mediterranean seabird species 期刊论文
GLOBAL CHANGE BIOLOGY, 2017, 23 (8)
作者:  Genovart, Meritxell;  Doak, Daniel F.;  Igual, Jose-Manuel;  Sponza, Stefano;  Kralj, Jelena;  Oro, Daniel
收藏  |  浏览/下载:19/0  |  提交时间:2019/04/09
bycatch  conservation  marine predators  multi-event capture-recapture  parameter uncertainty  population models  PVA  seabirds  stochasticity  survival