Nature Medicine Contents: March 2016 Volume 22 Number 3 pp 219-323

If you are unable to see the message below, click here to view.

Advertisement Apply precision medicine to advance your clinical trial outcomes  Power your precision medicine clinical trials with  genomic solutions  Download our complimentary precision medicine  white paper now TABLE OF CONTENTS March 2016 Volume 22, Issue 3 Editorial News News and Views Perspective Brief Communication Articles Letters Advertisement Key Advances in Medicine eBook from Nature Reviews - FREE to download!  This essential resource summarizes the groundbreaking clinical and biomedical discoveries of 2015 and highlights the trends to watch out for in 2016, making it a must read eBook for anyone with an interest in medical science.  Download for free   Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Molecular Diagnostics World Summit 2016 - Next Generation Diagnostics for Better Public Health (19-20 May 2016) This Conference brings together medical and clinical diagnostic professionals globally from Industry, Research and Government Agencies to share knowledge and collaborate to develop diagnostics to combat emerging diseases. Enter Promo code NATURE to avail £100 Discount - Register Today Deadlines: Abstracts & Discounts 15 March   Advertisement Nature Outlook Prostate Cancer Most men, if they live long enough, will get prostate cancer. New biomarker approaches promise more accurate prognoses, whereas treatment advances offer hope for metastatic cancers that so far have been beyond our control. Available free online. Produced with support from Ferring Pharmaceuticals and a grant from Astellas Pharma Global Development, Inc. and Medivation, Inc.     Advertisement Key Issues in Alzheimer's Disease- a community forum  Nature Neuroscience presents a forum on Alzheimer's Disease research. ACCESS NOW to view videos of our panel event at SfN 2015, read related articles for free, and post questions for our editors and featured experts. Produced with support from  Eli Lilly and Company and vTv Therapeutics     Editorial Top A modest proposal   p219 doi:10.1038/nm.4065 Amid heightened concerns about the Zika virus outbreak in parts of the Western Hemisphere, it is worth remembering that the most extreme countermeasures are not necessarily the only ones worth trying. We must engage in calculated and diverse responses that will ensure sustainable outcomes for this and other outbreaks. News Top News Features Back on TRAC: New trial launched in bid to outpace multidrug-resistant malaria   pp220 - 221 Amy Maxmen doi:10.1038/nm0316-220 Group mentality: Determining if targeted treatments really work for cancer   pp222 - 224 Shraddha Chakradhar doi:10.1038/nm0316-222 Missing link: Animal models to study whether Zika causes birth defects   pp225 - 227 Rachel Becker doi:10.1038/nm0316-225 News in Brief Biomedical briefing   pp228 - 229 doi:10.1038/nm0316-228 Opinion When patients reach out, scientists should reach back carefully   p230 Paul S Knoepfler doi:10.1038/nm0316-230 In the digital age, biomedical scientists are frequently contacted by lay individuals seeking medical help, but they still receive little, if any, training in how to respond. Researchers need to reach back to these patients, but in a way that steers clear of giving medical advice. News and Views Top First microbial encounters   pp231 - 232 Alexander Khoruts doi:10.1038/nm.4042 Altered microbial colonization associated with cesarean section (C-section) birth could potentially have adverse effects on host development. The first interventional study of its kind attempts to reconfigure the early microbiota composition in C-section-delivered newborns to resemble that associated with vaginal birth. See also: Brief Communication by Dominguez-Bello et al. The cellular origins of drug resistance in cancer   pp232 - 234 Geoffrey R Oxnard doi:10.1038/nm.4058 Two new studies show that mechanisms of acquired resistance to targeted therapy in lung cancer do not necessarily pre-exist in resistant subclones. Instead, some cancers may harbor the potential to acquire a variety of drug-resistance mechanisms after response to targeted therapy. See also: Article by Hata et al. Deriving functional beige fat from capillaries   pp234 - 236 Vanessa Pellegrinelli and Antonio Vidal-Puig doi:10.1038/nm.4056 In a recent study, beige adipocytes were derived from the capillaries of human subcutaneous adipose tissue. When implanted into mice, these cells enhanced glucose tolerance, thus providing evidence for their potential therapeutic use. See also: Letter by Min et al. Approaching a cure for type 1 diabetes   pp236 - 237 Qizhi Tang and Tejal A Desai doi:10.1038/nm.4060 A study has demonstrated that transplanting human embryonic stem cell-derived, insulin-producing cells shielded in capsules made with an optimized biomaterial can achieve long-term cure of diabetes in mice without the need for any immunosuppression. See also: Letter by Vegas et al. Nature Medicine JOBS of the week Faculty of Health Sciences and the Department of Pathology and Molecular Medicine Queen's University Assistant, Associate or Full Professor of Medicine (Biostatistician) University of Central Florida Head, Division of Solid Tumor Oncology, Department of Medicine Memorial Sloan Kettering Cancer Center (MSKCC) Postdoctoral Position in Department of Immunology, School of Medicine UConn Health Center PhD programs of the Faculty of Medicine Geneva University of Geneva, Faculty of Medicine More Science jobs from Nature Medicine EVENT More science events from Perspective Top Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants   pp238 - 249 Ronald S Duman, George K Aghajanian, Gerard Sanacora and John H Krystal doi:10.1038/nm.4050 Ron Duman and colleagues discuss recent insights into a role for circuit disruption in the mechanisms of stress-induced depression. Furthermore they discuss the potential for rapid-acting antidepressants to alleviate these defects. Brief Communication Top Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer   pp250 - 253 Maria G Dominguez-Bello, Kassandra M De Jesus-Laboy, Nan Shen, Laura M Cox, Amnon Amir et al. doi:10.1038/nm.4039 The microbiota of cesarean-born infants can be partially restored to that of vaginally born infants immediately after birth. See also: News and Views by Khoruts Advertisement Roles for mesenchymal stem cells as medicinal signaling cells Understanding the in vivo identity and function of mesenchymal stem cells (MSCs) is vital to fully exploit their therapeutic potential. This poster summarizes current thinking regarding the role of MSCs in vivo and also describes how to isolate MSCs and grow them in vitro. Download the poster free online. Produced with support from:  STEMCELL Technologies     Articles Top Rescue of GABAB and GIRK function in the lateral habenula by protein phosphatase 2A inhibition ameliorates depression-like phenotypes in mice   pp254 - 261 Salvatore Lecca, Assunta Pelosi, Anna Tchenio, Imane Moutkine, Rafael Lujan et al. doi:10.1038/nm.4037 Dysregulated GABA-GIRK signaling drives lateral habenula hyperactivity in mouse models of depression. Restoring GABA-GIRK signaling by treatment with a PP2A inhibitor alleviates depression-like phenotypes. Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition   pp262 - 269 Aaron N Hata, Matthew J Niederst, Hannah L Archibald, Maria Gomez-Caraballo, Faria M Siddiqui et al. doi:10.1038/nm.4040 Drug-tolerant but initially EGFRT790M-negative tumor cells that undergo genetic evolution to acquire resistance to EGFR inhibitors are more resistant than pre-existing EGFRT790M -positive clones to subsequent therapy. See also: News and Views by Oxnard Combined inhibition of DDR1 and Notch signaling is a therapeutic strategy for KRAS-driven lung adenocarcinoma   pp270 - 277 Chiara Ambrogio, Gonzalo Gomez-Lopez, Mattia Falcone, August Vidal, Ernest Nadal et al. doi:10.1038/nm.4041 Transcriptional profiling of Kras-driven early lesions—aimed at identifying founder events&mdash:reveals DDR1 as a therapeutic target relevant to adenocarcinoma. CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma   pp278 - 287 Elisa M Noll, Christian Eisen, Albrecht Stenzinger, Elisa Espinet, Alexander Muckenhuber et al. doi:10.1038/nm.4038 Expression of HNF1A and KRT81 stratifies pancreatic ductal adenocarcinoma tumors into different subtypes, and expression of cytochrome P450 3A5 mediates basal and/or drug-induced therapy resistance in each subtype. Rps14 haploinsufficiency causes a block in erythroid differentiation mediated by S100A8 and S100A9   pp288 - 297 Rebekka K Schneider, Monica Schenone, Monica Ventura Ferreira, Rafael Kramann, Cailin E Joyce et al. doi:10.1038/nm.4047 In a mouse model of the 5q- subtype of myelodysplastic syndrome, haploinsufficiency of the ribosomal protein gene Rps14 leads to anemia through a mechanism involving innate immune signaling and the Tlr4 ligand S100A8, which induces a p53-dependent block to erythroid differentiation. Advertisement This special Focus highlights the unprecedented insights gained into the regulatory mechanisms underlying nuclear reprogramming, pluripotency and cell identity, and looks at the progress and challenges in using embryonic stem (ES) cells and iPSCs for therapeutic applications. Available free online.  Produced with support from: Thermo Fisher Scientific     Letters Top Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer   pp298 - 305 Himisha Beltran, Davide Prandi, Juan Miguel Mosquera, Matteo Benelli, Loredana Puca et al. doi:10.1038/nm.4045 Genome-wide DNA methylation analysis of metastatic biopsies from patients with castration-resistant prostate cancer reveals marked epigenetic differences between samples with adenocarcinoma and neuroendocrine histologies. Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice   pp306 - 311 Arturo J Vegas, Omid Veiseh, Mads Gurtler, Jeffrey R Millman, Felicia W Pagliuca et al. doi:10.1038/nm.4030 When encapsulated with alginate derivatives that resist the foreign-body response, human embryonic stem cell-derived beta cells restore long-term normoglycemia in immunocompetent mice without the need for immunosuppression. See also: News and Views by Tang & Desai Human 'brite/beige' adipocytes develop from capillary networks, and their implantation improves metabolic homeostasis in mice   pp312 - 318 So Yun Min, Jamie Kady, Minwoo Nam, Raziel Rojas-Rodriguez, Aaron Berkenwald et al. doi:10.1038/nm.4031 Human beige adipocyte precursors associated with capillary networks proliferate in response to angiocrines, and when activated in vitro and transplanted into mice, they improve glucose intolerance. See also: News and Views by Pellegrinelli & Vidal-Puig Transient inhibition of ROR-γt therapeutically limits intestinal inflammation by reducing TH17 cells and preserving group 3 innate lymphoid cells   pp319 - 323 David R Withers, Matthew R Hepworth, Xinxin Wang, Emma C Mackley, Emily E Halford et al. doi:10.1038/nm.4046 Inhibition of ROR-γt impairs TH17 responses, but not innate lymphoid cells, and is therapeutically effective in mouse models of intestinal inflammation. Top Advertisement The Geoffrey Beene Cancer Research Center at Memorial Sloan Kettering Cancer Center, Nature, Nature Cell Biology and Nature Reviews Cancer present: CANCER AS AN EVOLVING AND SYSTEMIC DISEASE March 12-15, 2016 | New York, NY, USA 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

You have been sent this Table of Contents Alert because you have opted in to receive it. You can change or discontinue your e-mail alerts at any time, by modifying your preferences on your nature.com account at: www.nature.com/myaccount (You will need to log in to be recognised as a nature.com registrant) For further technical assistance, please contact our registration department For print subscription enquiries, please contact our subscription department For other enquiries, please contact our customer feedback department Nature Publishing Group | One New York Plaza, Suite 4500 | New York | NY 10004-1562 | USA Nature Publishing Group's worldwide offices: London - Paris - Munich - New Delhi - Tokyo - Melbourne San Diego - San Francisco - Washington - New York - Boston Macmillan Publishers Limited is a company incorporated in England and Wales under company number 785998 and whose registered office is located at Brunel Road, Houndmills, Basingstoke, Hampshire RG21 6XS. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.