GSTDTAP

浏览/检索结果: 共29条,第1-10条 帮助

已选(0)清除 条数/页:   排序方式:
IGF1R is an entry receptor for respiratory syncytial virus 期刊论文
NATURE, 2020, 583 (7817) : 615-+
作者:  Pasquina-Lemonche, L.;  Burns, J.;  Turner, R. D.;  Kumar, S.;  Tank, R.;  Mullin, N.;  Wilson, J. S.;  Chakrabarti, B.;  Bullough, P. A.;  Foster, S. J.;  Hobbs, J. K.
收藏  |  浏览/下载:36/0  |  提交时间:2020/07/03

Respiratory syncytial virus enters cells by binding to cell-surface IGFR1, which activates PKC zeta and induces trafficking of the NCL coreceptor to the RSV particles at the cell surface.


Pneumonia resulting from infection is one of the leading causes of death worldwide. Pulmonary infection by the respiratory syncytial virus (RSV) is a large burden on human health, for which there are few therapeutic options(1). RSV targets ciliated epithelial cells in the airways, but how viruses such as RSV interact with receptors on these cells is not understood. Nucleolin is an entry coreceptor for RSV2 and also mediates the cellular entry of influenza, the parainfluenza virus, some enteroviruses and the bacterium that causes tularaemia(3,4). Here we show a mechanism of RSV entry into cells in which outside-in signalling, involving binding of the prefusion RSV-F glycoprotein with the insulin-like growth factor-1 receptor, triggers the activation of protein kinase C zeta (PKC zeta). This cellular signalling cascade recruits nucleolin from the nuclei of cells to the plasma membrane, where it also binds to RSV-F on virions. We find that inhibiting PKC zeta activation prevents the trafficking of nucleolin to RSV particles on airway organoid cultures, and reduces viral replication and pathology in RSV-infected mice. These findings reveal a mechanism of virus entry in which receptor engagement and signal transduction bring the coreceptor to viral particles at the cell surface, and could form the basis of new therapeutics to treat RSV infection.


  
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:36/0  |  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).


  
Feeding-dependent VIP neuron-ILC3 circuit regulates the intestinal barrier 期刊论文
NATURE, 2020, 579 (7800) : 575-+
作者:  Bhaduri, Aparna;  Andrews, Madeline G.;  Mancia Leon, Walter;  Jung, Diane;  Shin, David;  Allen, Denise;  Jung, Dana;  Schmunk, Galina;  Haeussler, Maximilian;  Salma, Jahan;  Pollen, Alex A.;  Nowakowski, Tomasz J.;  Kriegstein, Arnold R.
收藏  |  浏览/下载:53/0  |  提交时间:2020/07/03

The intestinal mucosa serves both as a conduit for the uptake of food-derived nutrients and microbiome-derived metabolites, and as a barrier that prevents tissue invasion by microorganisms and tempers inflammatory responses to the myriad contents of the lumen. How the intestine coordinates physiological and immune responses to food consumption to optimize nutrient uptake while maintaining barrier functions remains unclear. Here we show in mice how a gut neuronal signal triggered by food intake is integrated with intestinal antimicrobial and metabolic responses that are controlled by type-3 innate lymphoid cells (ILC3)(1-3). Food consumption rapidly activates a population of enteric neurons that express vasoactive intestinal peptide (VIP)(4). Projections of VIP-producing neurons (VIPergic neurons) in the lamina propria are in close proximity to clusters of ILC3 that selectively express VIP receptor type 2 (VIPR2  also known as VPAC2). Production of interleukin (IL)-22 by ILC3, which is upregulated by the presence of commensal microorganisms such as segmented filamentous bacteria(5-7), is inhibited upon engagement of VIPR2. As a consequence, levels of antimicrobial peptide derived from epithelial cells are reduced but the expression of lipid-binding proteins and transporters is increased(8). During food consumption, the activation of VIPergic neurons thus enhances the growth of segmented filamentous bacteria associated with the epithelium, and increases lipid absorption. Our results reveal a feeding- and circadian-regulated dynamic neuroimmune circuit in the intestine that promotes a trade-off between innate immune protection mediated by IL-22 and the efficiency of nutrient absorption. Modulation of this pathway may therefore be effective for enhancing resistance to enteropathogens(2,3,9) and for the treatment of metabolic diseases.


Feeding controls a neuroimmune circuit comprising VIP-producing neurons and type-3 innate lymphoid cells that helps to regulate the efficiency of nutrient uptake and IL-22-mediated immune protection in the intestine.


  
Scientists' incentives and attitudes toward public communication 期刊论文
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 117 (3) : 1274-1276
作者:  Rose, Kathleen M.;  Markowitz, Ezra M.;  Brossard, Dominique
收藏  |  浏览/下载:15/0  |  提交时间:2020/05/13
science communication  engagement with science  public universities  
You can't fight feelings with facts: start with a chat 期刊论文
NATURE, 2020, 578 (7795) : 339-339
作者:  Kosik, Kenneth S.
收藏  |  浏览/下载:22/0  |  提交时间:2020/07/03

I donned a sandwich board inviting questions on evolution and learnt three crucial lessons about public engagement on divisive issues, writes Maggie Ryan Sandford.


I donned a sandwich board inviting questions on evolution and learnt three crucial lessons about public engagement on divisive issues, writes Maggie Ryan Sandford.


  
Engendering an inclusive low-carbon energy transition in Japan: Considering the perspectives and awareness of the energy poor 期刊论文
ENERGY POLICY, 2019, 135
作者:  Chapman, Andrew;  Okushima, Shinichiro
收藏  |  浏览/下载:30/0  |  提交时间:2020/02/17
Awareness  Climate change policy  Energy poverty  Energy transition  Renewable policy  Stakeholder engagement  
Beyond participation: when citizen engagement leads to undesirable outcomes for nature-based solutions and climate change adaptation 期刊论文
CLIMATIC CHANGE, 2019
作者:  Wamsler, C.;  Alkan-Olsson, J.;  Bjorn, H.;  Falck, H.;  Hanson, H.;  Oskarsson, T.;  Simonsson, E.;  Zelmerlow, F.
收藏  |  浏览/下载:17/0  |  提交时间:2020/02/17
Nature-based solutions  Ecosystem services  Ecosystem-based adaptation  Ecosystem-based planning  Emotions  Climate change adaptation  Disaster risk reduction  Citizen participation  Collaborative governance  Sustainability  Co-Production  Citizen science  Values  Citizen engagement  Public participation  
Rethinking Australian CSG transitions in participatory contexts of local social conflict, community engagement, and shifts towards cleaner energy 期刊论文
ENERGY POLICY, 2019, 132: 272-282
作者:  Hindmarsh, Richard;  Alidoust, Sara
收藏  |  浏览/下载:15/0  |  提交时间:2019/11/27
Coal seam gas  Social conflict  Participatory  Community engagement  Energy transitions  Australia  
The role of landscape installations in climate change communication 期刊论文
LANDSCAPE AND URBAN PLANNING, 2019, 189: 11-14
作者:  Aragon, Carolina;  Buxton, Jane;  Infield, Elisabeth Hamin
收藏  |  浏览/下载:12/0  |  提交时间:2019/11/27
Climate change communication  Landscape installations  Public art  Public engagement  
Investing in a good pair of wellies: how do non-experts interpret the expert terminology of climate change impacts and adaptation? 期刊论文
CLIMATIC CHANGE, 2019, 155 (2) : 257-272
作者:  Harcourt, Rachel;  de Bruin, Wandi Bruine;  Dessai, Suraje;  Taylor, Andrea
收藏  |  浏览/下载:17/0  |  提交时间:2019/11/27
Climate change impacts  Adaptation  Science communication  Public engagement  Responsibility