Nature Medicine Contents: May 2017 Volume 23 Number 5 pp 527-643

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Advertisement Call for Applications: The 2018 Vilcek Prizes for Creative Promise in Biomedical Science $150,000 in cash awards for three young, foreign-born researchers Learn more about eligibility requirements and apply at Vilcek.org Deadline: May 31, 2017 TABLE OF CONTENTS May 2017 Volume 23, Issue 5 Editorial News Correction News and Views Perspective Brief Communications Articles Letters Advertisement   New Gene Editing Technology Now Available! Canopy Biosciences is excited to introduce a new gene editing technology--the TUNR Flexible Gene Editing System. The TUNR system leverages CRISPR-Cas9 and allows you to generate cell lines or animal models with a range of expression of your targeted gene. To find out more, visit our website at www.canopybiosciences.com Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Outlook: Regenerative Medicine  Sometimes, a drug can remedy a chemical imbalance or surgery can repair a structural failure, but there are times when there is no substitute for replacing a part with human tissue or an entire organ. Rapid advances in regenerative medicine are bringing that possibility closer to reality. Access the Outlook Produced with support from  Translational Research Informatics Center(TRI)  Clio, Inc.  Sapporo Medical University  CYBERDYNE,INC.   Advertisement Animation: Alzheimer's disease  Nature Neuroscience presents this animation, which introduces the molecular, cellular and physiological mechanisms associated with Alzheimer's disease and highlights some of the most recent advances in our understanding of the onset and progression of this devastating neurological condition.  Watch the Animation free online >>   Advertisement REGENERATION 2017 Presented by: Ospedale San Raffaele | Nature The conference will feature sessions on regeneration in animal models, functional and dysfunctional regeneration in mammals, and new therapeutic approaches to regeneration. November 16-18, 2017 | Milan, Italy REGISTER NOW!   Editorial Top The curse of uncertainty   p527 doi:10.1038/nm.4342 Proposed US budget cuts and the impending exit of the UK from the European Union have the potential to destabilize the global biomedical-research enterprise. In the meantime, the uncertainty of not knowing just how bad the effects will be will inflict its own damage. News Top Host with the most: Targeting host cells instead of pathogens to fight infectious disease   pp528 - 531 Amanda B. Keener doi:10.1038/nm0517-528 Bringing RNA into the fold: Small molecules find new targets in RNA to combat disease   pp532 - 534 Shraddha Chakradhar doi:10.1038/nm0517-532 Correction Top Correction   p534 doi:10.1038/nm0517-534 News and Views Top A role for oncostatin M in inflammatory bowel disease   pp535 - 536 Walter M Kim, Arthur Kaser and Richard S Blumberg doi:10.1038/nm.4338 A new study identifies oncostatin M (OSM) as a potential biomarker and therapeutic target for anti-tumor necrosis factor (TNF)-refractory inflammatory bowel disease (IBD), and pinpoints mucosal stromal cells as key players in OSM-mediated inflammation. See also: Article by West et al. Thymosin α1: a single drug with multiple targets in cystic fibrosis   pp536 - 538 Andre M Cantin and John W Hanrahan doi:10.1038/nm.4339 A new study in mice suggests that a single drug, thymosin α1, may simultaneously rectify the impaired trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) in cystic fibrosis (CF) and reduce inflammation, offering new hope for CF treatment. See also: Article by Romani et al. HIV persistence in macrophages   pp538 - 539 Mario Stevenson doi:10.1038/nm.4337 A recent study using a humanized mouse model shows that HIV-1 can persist in macrophages during antiretroviral therapy (ART), and suggests that macrophages may represent an obstacle to efforts to cure HIV-1 infection. See also: Letter by Honeycutt et al. Nature Medicine JOBS of the week Tenure Track Faculty Research Physician for the Center for Translational Medicine - Neurodegeneration Temple University School of Medicine Assistant Professor - Faculty of Veterinary Medicine - University of Calgary University of Calgary Cheeloo College of Medicine(CCOM), Shandong University Recruit Outstanding Talents Cheeloo College of Medicine(CCOM), Shandong University Postdoctoral Fellow / Preventive Medicine The University of Tennessee Health Science Center NIH T32 Training Grant in Pediatric Pulmonary Medicine University of Pittsburgh More Science jobs from Nature Medicine EVENT Mayo Clinic Updates in Internal Medicine 2017 19.10.17 Lake Buena Vista, USA More science events from Perspective Top Is autoimmunity the Achilles' heel of cancer immunotherapy?   pp540 - 547 Carl H June, Jeremy T Warshauer and Jeffrey A Bluestone doi:10.1038/nm.4321 In this Perspective, June, Bluestone and Warshauer discuss potential cellular and molecular explanations for the autoimmunity often associated with immunotherapy, and propose additional research and changes to reporting practices to aid efforts to understand and minimize these toxic side effects. Brief Communications Top Diagnosis of Zika virus infection on a nanotechnology platform   pp548 - 550 Bo Zhang, Benjamin A Pinsky, Jeyarama S Ananta, Su Zhao, Shylaja Arulkumar et al. doi:10.1038/nm.4302 Antibody-based diagnosis of Zika virus (ZIKV) infection is complicated by cross-reactivity with antibodies against dengue virus. Hongjie Dai and colleagues report their development of a new IgA- and IgG-based diagnostic test that detects ZIKV with high specificity. VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer   pp551 - 555 Jianjun Gao, John F Ward, Curtis A Pettaway, Lewis Z Shi, Sumit K Subudhi et al. doi:10.1038/nm.4308 Prostate cancer is refractory to anti-CTLA-4 therapy, but the reason why is unclear. Padmanee Sharma and colleagues report that the inhibitory molecule VISTA, which negatively regulates T cells, is upregulated on macrophages in prostate tumors that have been treated with anti-CTLA-4 and may play a role in resistance to this immunotherapy. Advertisement Nature Milestones: Interactive antibody timeline Nature Milestones: Antibodies presents an interactive timeline on the history of antibodies covering everything from their initial description in antisera through to their application in immunotherapy. The timeline includes written content, video interviews and animations.  Access the timeline free online Produced with support from BioLegend UCB    Articles Top Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance   pp556 - 567 Donnele Daley, Vishnu R Mani, Navyatha Mohan, Neha Akkad, Atsuo Ochi et al. doi:10.1038/nm.4314 Activation of dectin-1-dependent signaling in macrophages through ligation by galectin 9 promotes an immunosuppressive, protumorigenic microenvironment in pancreatic adenocarcinoma (PDA). Blocking dectin 1 ligation restores anti-tumor immunity and delays tumor growth, thus offering a novel strategy for improving the effectiveness of immunotherapy in patients with PDA. A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability   pp568 - 578 Anne-Pierre Morel, Christophe Ginestier, Roxane M Pommier, Olivier Cabaud, Emmanuelle Ruiz et al. doi:10.1038/nm.4323 During malignant transformation, the ability of mammary epithelial cells to cope with oncogene-induced DNA damage and avoid chromosomal instability is determined by stemness-related expression of the canonical epithelial-to-mesenchymal transition transcription factor ZEB1 and its target MSRB3, a methionine sulfoxide reductase involved in antioxidant defense. Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor-neutralizing therapy in patients with inflammatory bowel disease   pp579 - 589 Nathaniel R West, Ahmed N Hegazy, Benjamin M J Owens, Samuel J Bullers, Bryan Linggi et al. doi:10.1038/nm.4307 The cytokine oncostatin M drives intestinal inflammation in mice, and its abundance in the intestine of patients with inflammatory bowel disease predicts response to tumor necrosis factor-neutralizing therapy. See also: News and Views by Kim et al. Thymosin α1 represents a potential potent single-molecule-based therapy for cystic fibrosis   pp590 - 600 Luigina Romani, Vasilis Oikonomou, Silvia Moretti, Rossana G Iannitti, Maria Cristina D'Adamo et al. doi:10.1038/nm.4305 Thymosin α1 is used in the clinic as a treatment in viral disease and acts as an anti-inflammatory. Here it was found to also correct the misfolding of mutant CTFR and potentiate its activity, thus improving outcome in a mouse model of cystic fibrosis. See also: News and Views by Cantin & Hanrahan Marginal zone B cells control the response of follicular helper T cells to a high-cholesterol diet   pp601 - 610 Meritxell Nus, Andrew P Sage, Yuning Lu, Leanne Masters, Brian Y H Lam et al. doi:10.1038/nm.4315 Splenic marginal zone B cells suppress atherosclerosis in mice by dampening the proatherogenic T follicular helper response via a PDL1-dependent interaction with T follicular helper cells. A heart-brain-kidney network controls adaptation to cardiac stress through tissue macrophage activation   pp611 - 622 Katsuhito Fujiu, Munehiko Shibata, Yukiteru Nakayama, Fusa Ogata, Sahohime Matsumoto et al. doi:10.1038/nm.4326 The ability of the heart to withstand pressure overload, as occurs in heart failure, depends on a multi-organ circuit, in which sympathetic activation of the kidney leads to release of the cytokine CSF2 into the circulation, stimulating cardiac-resident macrophages that protect the heart. Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis   pp623 - 630 Katrin Fischer, Henry H Ruiz, Kevin Jhun, Brian Finan, Douglas J Oberlin et al. doi:10.1038/nm.4316 In contrast to previously reported findings, M2-like polarized macrophages are not a source of catecholamines and do not contribute to browning of the fat. Advertisement The 5th Helmholtz-Nature Medicine DIABETES CONFERENCE  September 17-19, 2017 | Munich, Germany Presented by: Helmholtz Zentrum Munchen | Nature Medicine REGISTER NOW!   Letters Top The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue   pp631 - 637 Matthew D Lynes, Luiz O Leiria, Morten Lundh, Alexander Bartelt, Farnaz Shamsi et al. doi:10.1038/nm.4297 Cold stimulation induces the synthesis and release of the lipid species 12,13-diHOME from brown adipose tissue. This /`lipokine/' then acts on brown adipocytes to promote the uptake of fatty acids to fuel this cell type's heat production. HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy   pp638 - 643 Jenna B Honeycutt, William O Thayer, Caroline E Baker, Ruy M Ribeiro, Steven M Lada et al. doi:10.1038/nm.4319 Persistence of HIV is attributed primarily to latent infection of CD4+ T cells. Honeycutt et al. report that in humanized mice lacking T cells HIV can rebound from myeloid cells after antiretroviral treatment interruption, suggesting that persistence of HIV could involve other cell types. See also: News and Views by Stevenson Top Advertisement IMMUNE PROFILING IN HEALTH AND DISEASE  September 17-19, 2017 | Seattle, WA, USA Presented by: Adaptive Biotechnologies | Nature Immunology | Nature Medicine | Nature Biotechnology REGISTER NOW!   Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com More Nature Events

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