Nature Medicine Contents: May 2015 Volume 21 Number 5 pp 415 - 537

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Advertisement The Harrington Prize for Innovation in Medicine - Nominations due August 28, 2015. The Harrington Prize for Innovation in Medicine, presented by the American Society for Clinical Investigation and the Harrington Discovery Institute, honors the physician-scientist who has moved science forward with notable achievements in innovation, creativity and potential for clinical application. The Harrington Prize includes an unrestricted $20,000 honorarium. Submit a nomination at http://www.HarringtonDiscovery.org. TABLE OF CONTENTS May 2015 Volume 21, Issue 5 Editorial News Correction News and Views Perspective Articles Letters Corrigenda Erratum Advertisement Precision Medicine Excellence EA | Quintiles combines comprehensive genomic technologies with clinical expertise to help you identify the right pathways, biomarkers and patient populations that will enable you to better predict the long-term safety and efficacy of your products. Click here to learn more.  Subscribe   Facebook   RSS   Recommend to library   Twitter   Podcast Editorial Top Immunotherapy: combine and conquer   p415 doi:10.1038/nm.3865 Recent clinical data suggest that combination immunotherapy may be the wave of the future. To capitalize on these exciting findings, the scientific, logistical, proprietary and financial hurdles to the clinical testing of combination therapy must be addressed. News Top News Features Buzzkill: Regulatory uncertainty plagues rollout of genetically modified mosquitoes   pp416 - 418 Shraddha Chakradhar doi:10.1038/nm0515-416 An unknown enemy: Drugs sought against EV-68 as paralysis link is explored   pp419 - 421 Cassandra Willyard doi:10.1038/nm.3846 News in Brief Biomedical briefing   pp422 - 423 doi:10.1038/nm0515-422 Correction Top Corrections   p423 doi:10.1038/nm0515-423 News and Views Top A B cell-dependent mechanism restrains T cell transendothelial migration   pp424 - 426 Julie D Saba doi:10.1038/nm.3858 A new study reveals that B cells restrict the transendothelial migration of T cells in physiological inflammation in response to adiponectin, but that this mechanism is compromised in autoimmunity and is hence a novel avenue for therapy development. See also: Article by Chimen et al. A cross-talk network that facilitates tumor virotherapy   pp426 - 427 Agnieszka Bronisz and E Antonio Chiocca doi:10.1038/nm.3857 To target and kill cancer cells, oncolytic viruses exploit signaling pathways that promote tumor growth. A new study shows that the cancer stromal fibroblast factor FGF2 is a crucial component of a tumor-TGF-[beta] axis that renders cancer cells sensitive to virus infection. See also: Letter by Ilkow et al. Duodenal energy sensing regulates hepatic glucose output   pp428 - 429 Brennan K Smith and Gregory R Steinberg doi:10.1038/nm.3859 The maintenance of blood glucose involves the coordination of multiple organ systems. Two new studies indicate that metformin and resveratrol activate metabolic sensors in the duodenum and initiate a neural loop that reduces liver glucose production in rat models of type 2 diabetes. See also: Letter by Cote et al. | Letter by Duca et al. Repurposing a leukocyte elastase inhibitor for neuropathic pain   pp429 - 430 Andy D Weyer and Cheryl L Stucky doi:10.1038/nm.3861 Neuropathic pain is a debilitating condition affecting millions of people worldwide. A new study investigates mechanisms of neuropathic pain initiation and identifies a promising therapeutic currently used for acute respiratory distress syndrome that may also limit acute neuropathic pain. See also: Letter by Vicuna et al. Nature Medicine JOBS of the week Post Doctoral Fellow Northwestern University- Feinberg School of Medicine Research Assistant / Associate University of Glasgow PhD fellowship Norwegian PSC research center Diabetes UK PhD Studentships Diabetes UK More Science jobs from Nature Medicine EVENT EMBO Practical Course: Two-photon imaging of brain function: From spiny dendrites to circuits 05.09.15 Munich, Germany More science events from Perspective Top Translational value of mouse models in oncology drug development   pp431 - 439 Stephen E Gould, Melissa R Junttila and Frederic J de Sauvage doi:10.1038/nm.3853 In this Perspective, Fred De Sauvage and Stephen Gould discuss the suitability of different mouse models for modeling cancer pathogenic processes, with an emphasis on applicability to developing cancer therapies. Articles Top Studying clonal dynamics in response to cancer therapy using high-complexity barcoding   pp440 - 448 Hyo-eun C Bhang, David A Ruddy, Viveksagar Krishnamurthy Radhakrishna, Justina X Caushi, Rui Zhao et al. doi:10.1038/nm.3841 The authors have developed a barcoded library that enables the high-throughput tracking of tumor cell dynamics and clonal evolution in response to therapy. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes   pp449 - 456 Razvan Cristescu, Jeeyun Lee, Michael Nebozhyn, Kyoung-Mee Kim, Jason C Ting et al. doi:10.1038/nm.3850 By using gene expression data, gastric cancer is divided into subtypes associated with distinct molecular alterations and clinical prognosis. Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer   pp457 - 466 Shuo Wei, Shingo Kozono, Lev Kats, Morris Nechama, Wenzong Li et al. doi:10.1038/nm.3839 All-trans retinoic acid binds to, inhibits and induces degradation of the active form of the prolyl isomerase Pin1, thereby turning off and on a variety of Pin1 substrate oncogenes and tumor suppressors, respectively. Homeostatic regulation of T cell trafficking by a B cell-derived peptide is impaired in autoimmune and chronic inflammatory disease   pp467 - 475 Myriam Chimen, Helen M McGettrick, Bonita Apta, Sahithi J Kuravi, Clara M Yates et al. doi:10.1038/nm.3842 B cell-mediated inhibition of T cell trafficking is impaired in inflammatory disease. See also: News and Views by Saba Photovoltaic restoration of sight with high visual acuity   pp476 - 482 Henri Lorach, Georges Goetz, Richard Smith, Xin Lei, Yossi Mandel et al. doi:10.1038/nm.3851 A photovoltaic retinal prosthesis activated by light restores half of normal visual acuity in rats blinded by retinal degeneration. Slit2 signaling through Robo1 and Robo2 is required for retinal neovascularization   pp483 - 491 Nicolas Rama, Alexandre Dubrac, Thomas Mathivet, Roisin-Ana Ni Charthaigh, Gael Genet et al. doi:10.1038/nm.3849 Slit ligand-Robo receptor signaling is needed for developmental angiogenesis in the retina and represents a therapeutic target in ocular neovascular diseases. Letters Top An RNAi therapeutic targeting antithrombin to rebalance the coagulation system and promote hemostasis in hemophilia   pp492 - 497 Alfica Sehgal, Scott Barros, Lacramioara Ivanciu, Brian Cooley, June Qin et al. doi:10.1038/nm.3847 An siRNA targeting antithrombin promotes hemostasis in mouse and nonhuman primate models of hemophilia and could represent a new therapeutic option for this disease. Resveratrol activates duodenal Sirt1 to reverse insulin resistance in rats through a neuronal network   pp498 - 505 Clemence D Cote, Brittany A Rasmussen, Frank A Duca, Melika Zadeh-Tahmasebi, Joseph A Baur et al. doi:10.1038/nm.3821 Two papers show that Ampk and Sirt1 respond to metformin and resveratrol, respectively, in the duodenum to initiate a gut-brain-liver axis that reduces hepatic glucose production, thus explaining the antidiabetic actions of these two class of drugs. See also: News and Views by Smith & Steinberg | Letter by Duca et al. Metformin activates a duodenal Ampk-dependent pathway to lower hepatic glucose production in rats   pp506 - 511 Frank A Duca, Clemence D Cote, Brittany A Rasmussen, Melika Zadeh-Tahmasebi, Guy A Rutter et al. doi:10.1038/nm.3787 Two papers show that Ampk and Sirt1 respond to metformin and resveratrol, respectively, in the duodenum to initiate a gut-brain-liver axis that reduces hepatic glucose production, thus explaining the antidiabetic actions of these two class of drugs. See also: News and Views by Smith & Steinberg | Letter by Cote et al. Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion   pp512 - 517 Caroline Bonner, Julie Kerr-Conte, Valery Gmyr, Gurvan Queniat, Ericka Moerman et al. doi:10.1038/nm.3828 The recently approved drug dapagliflozin is now shown to increase glucagon secretion by acting on pancreatic alpha cells, which has implications for the potency of its antidiabetic effects The serine protease inhibitor SerpinA3N attenuates neuropathic pain by inhibiting T cell-derived leukocyte elastase   pp518 - 523 Lucas Vicuna, David E Strochlic, Alban Latremoliere, Kiran Kumar Bali, Manuela Simonetti et al. doi:10.1038/nm.3852 Inhibition of T cell-derived leukocyte elastase by neuronal SerpinA3N or the drug Sivelestat reduces neuropathic pain. See also: News and Views by Weyer & Stucky Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes   pp524 - 529 Ignazio Caruana, Barbara Savoldo, Valentina Hoyos, Gerrit Weber, Hao Liu et al. doi:10.1038/nm.3833 Gianpietro Dotti and colleagues report that CAR-T cells expressing heparanase to degrade the extracellular matrix may enhance their infiltration of and effects on solid tumors. Reciprocal cellular cross-talk within the tumor microenvironment promotes oncolytic virus activity   pp530 - 536 Carolina S Ilkow, Monique Marguerie, Cory Batenchuk, Justin Mayer, Daniela Ben Neriah et al. doi:10.1038/nm.3848 John Bell and colleagues report that cross-talk between tumor and cancer-associated fibroblasts mediated by FGF2 can enhance efficacy of oncolytic virotherapy. See also: News and Views by Bronisz & Chiocca Corrigenda Top Corrigendum: PAI-1 mediates the antiangiogenic and profibrinolytic effects of 16K prolactin   p537 Khalid Bajou, Stephanie Herkenne, Victor L Thijssen, Salvino D'Amico, Ngoc-Quynh-Nhu Nguyen et al. doi:10.1038/nm0515-537a Corrigendum: Remote regulation of glucose homeostasis in mice using genetically encoded nanoparticles   p537 Sarah A Stanley, Jeremy Sauer, Ravi S Kane, Jonathan S Dordick and Jeffrey M Friedman doi:10.1038/nm0515-537b Corrigendum: Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice   p537 Nicolas Wein, Adeline Vulin, Maria S Falzarano, Christina Al-Khalili Szigyarto, Baijayanta Maiti et al. doi:10.1038/nm0515-537c Erratum Top Erratum: Error in March 2015 cover caption   p537 doi:10.1038/nm0515-537d Top Advertisement Innovations in the Microbiome Tending the garden within  •  Can good microbes improve our health?  •  Does our gut govern the state of our mind?  •  Can smart bacteria treat disease? 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