Nature Medicine Contents: November 2016 Volume 22 Number 11 pp 1193-1367

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Advertisement QScience.com Highlights is a regularly updated online platform which highlights the best of published research, handpicked by Nature Journals' editors, from QScience.com. Stay up-to-date with the latest research and reviews qscience.nature.com TABLE OF CONTENTS November 2016 Volume 22, Issue 11 Editorials Correction News Correspondence News and Views Perspectives Brief Communication Articles Letters Analysis Technical Reports Advertisement Nature Outlook: Pain Nature Outlook: Pain presents the latest research into the causes of, and treatments for, chronic and neuropathic pain, allowing you to stay up to date on the biggest developments within the field of pain.  Access the Outlook free online for six months. Produced with support from ESTEVE, Mundipharma International Limited and Mundipharma Research GmbH & Co. KG Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Index 2016 Rising Stars:  The Nature Index 2016: Rising Stars supplement identifies the people and organizations that have the potential to ascend within the world of science. The rising stars are identified by harnessing the power of the Nature Index, which tracks high-quality research of over 8,000 global institutions. Access the free supplement in full today!   Advertisement Open for Submissions  Online-only and open access, npj Primary Care Respiratory Medicine is the only fully-indexed scientific journal devoted to the management of respiratory diseases in primary care. Explore the benefits of submitting your next research article >>   Advertisement Open for Submissions  npj Precision Oncology is a new open access, online-only, peer-reviewed journal committed to publishing cutting-edge scientific research in all aspects of precision oncology from basic science to translational applications, to clinical medicine. The journal is part of the Nature Partner Journals series and published in partnership with The Hormel Institute, University of Minnesota.  Explore the benefits of submitting your manuscript >>   Editorials Top Railroading at the FDA   p1193 doi:10.1038/nm.4234 The US Food and Drug Administration approved a muscular-dystrophy drug against the scientific advice of its own staff and advisors. Despite leadership's attempts to downplay the controversy, doubts now surround standards for accelerated approval. Mental health horizons   p1213 doi:10.1038/nm.4235 From organoids to population-level studies, mental health research has begun to crack long-standing mysteries. Longitudinal investigations into brain and cognitive development among adolescents, such as the forthcoming 10,000-person ABCD project, will help to mature the field. Correction Top Correction   p1202 doi:10.1038/nm1116-1202 News Top News Features Shapeshifters in cancer: How some tumor cells change phenotype to evade therapy   pp1194 - 1196 Amanda B Keener doi:10.1038/nm1116-1194 What's old is new: Reconfiguring known antibiotics to fight drug resistance    pp1197 - 1199 Shraddha Chakradhar doi:10.1038/nm1116-1197 New models: Gene-editing boom means changing landscape for primate work    pp1200 - 1202 Cassandra Willyard doi:10.1038/nm1116-1200 Correspondence Top PPAR-γ regulates pharmacological but not physiological or pathological osteoclast formation   pp1203 - 1205 Wei Zou, Nidhi Rohatgi, Timothy Hung-Po Chen, Joel Schilling, Yousef Abu-Amer et al. doi:10.1038/nm.4208 Reply to "PPAR-γ regulates pharmacological but not physiological or pathological osteoclast formation"   p1205 Ronald M Evans and Yihong Wan doi:10.1038/nm.4207 News and Views Top Increasing the neurological-disease toolbox using iPSC-derived microglia   pp1206 - 1207 Timothy R Hammond and Beth Stevens doi:10.1038/nm.4226 A new study presents a protocol to differentiate human induced pluripotent stem cells (iPSCs) into microglia that closely resemble their in vivo counterparts. These cells offer an exciting new tool for learning more about the role of microglia in disease. See also: Technical Report by Muffat et al. Caspase-2 and tau—a toxic partnership?   pp1207 - 1208 Carol M Troy and Michael L Shelanski doi:10.1038/nm.4227 Misfolded and hyperphosphorylated forms of the microtubule-associated protein tau are thought to be responsible for some degree of neurodegeneration. The demonstration of a novel toxic cleavage of tau by caspase-2 opens up new therapeutic avenues. See also: Article by Zhao et al. Improving treatment of liver metastases by targeting nonangiogenic mechanisms   pp1209 - 1210 Kyrre E Emblem and Rakesh K Jain doi:10.1038/nm.4228 A recent study confirms an association between vessel co-option and resistance to bevacizumab, an anti-vascular endothelial growth factor-A (VEGFA) antibody, in patients with liver metastases. The authors suggest a combined therapeutic strategy that reduces co-option in mice. See also: Article by Frentzas et al. Innate immune signaling and stem cell renewal in idiopathic pulmonary fibrosis   pp1210 - 1212 Paul F Mercer and Rachel C Chambers doi:10.1038/nm.4230 Aberrant injury responses in the distal lung likely underpin the development of idiopathic pulmonary fibrosis (IPF). A recent study shows that defective Toll-like receptor 4 (TLR4)-mediated hyaluronan binding impairs alveolar type 2 cell renewal, which may contribute to a dysregulated lung-injury response in IPF. See also: Article by Liang et al. Nature Medicine JOBS of the week Two Assistant Professor Positions in Molecular Medicine University of Georgia Center for Molecular Medicine Acquisitions Editor, Clinical Medicine Springer Nature Assistant / Associate Professor Arizona State University, Center for Evolution & Medicine Open Rank Faculty Position - Prevention Research The Stanford Prevention Research Center, in the Department of Medicine More Science jobs from Nature Medicine EVENT More science events from Perspectives Top The implications of the shared genetics of psychiatric disorders   pp1214 - 1219 Michael C O'Donovan and Michael J Owen doi:10.1038/nm.4196 Recent studies have led to the identification of genetic loci that are shared between psychiatric disorders. Here O/'Donovan and Owen argue that it is unlikely that risk alleles exist that are singular to any one such disorder. The promises and challenges of human brain organoids as models of neuropsychiatric disease   pp1220 - 1228 Giorgia Quadrato, Juliana Brown and Paola Arlotta doi:10.1038/nm.4214 Psychiatric disorders are difficult to model owing to their inherent complexity and heterogeneity. This Perspective focuses on the use of 3D brain organoids in modeling these disorders, considering both their advantages and their limitations. Developmental timing and critical windows for the treatment of psychiatric disorders   pp1229 - 1238 Oscar Marin doi:10.1038/nm.4225 The developmental trajectories of neuropsychiatric disorders suggest that early life events might contribute substantially to disease. Here the author discusses the potential to treat within these critical time windows of development to alter disease course. Re-evaluating the link between neuropsychiatric disorders and dysregulated adult neurogenesis   pp1239 - 1247 Sanghee Yun, Ryan P Reynolds, Irene Masiulis and Amelia J Eisch doi:10.1038/nm.4218 Recent evidence indicates that one of the underlying mechanisms in the pathogenesis of neuropsychiatric disorders is dysregulated dentate gyrus neurogenesis. Here the authors present evidence supporting this hypothesis and suggest therapeutic avenues. The search for imaging biomarkers in psychiatric disorders   pp1248 - 1255 Anissa Abi-Dargham and Guillermo Horga doi:10.1038/nm.4190 Abi-Dargham and Horga discuss the challenges of developing and standardizing brain-imaging technologies to aid with the diagnosis and treatment of psychiatric disorders. Brief Communication Top Fetal brain lesions after subcutaneous inoculation of Zika virus in a pregnant nonhuman primate   pp1256 - 1259 Kristina M Adams Waldorf, Jennifer E Stencel-Baerenwald, Raj P Kapur, Colin Studholme, Erica Boldenow et al. doi:10.1038/nm.4193 New animal models of Zika virus (ZIKV) infection are imperative to accelerating efforts to treat or prevent disease in humans. Adams Waldorf et al. now report that ZIKV infection of a pregnant female pigtailed macaque caused brain lesions in the developing fetus, suggesting that this model may be useful for understanding ZIKV-associated congenital abnormalities in humans. Advertisement Focus on Psychiatric Disorders Compared to other areas, psychiatric research faces unique biological, technological, clinical, regulatory and ethical challenges. In this focus Nature Neuroscience and Nature Medicine present a collection of Commentaries, Perspectives, and Reviews that address these challenges. Access the Focus online Produced with support of a grant from:  Avanir Pharmaceuticals, Inc.     Articles Top Determinants of HIV-1 broadly neutralizing antibody induction   pp1260 - 1267 Peter Rusert, Roger D Kouyos, Claus Kadelka, Hanna Ebner, Merle Schanz et al. doi:10.1038/nm.4187 Broadly neutralizing antibodies (bnAbs) develop in a minority of HIV-infected individuals. Analyzing data from more than 4,000 infected individuals, Alexandra Trkola and colleagues identify viral, host and disease factors associated with the development of bNAbs that may inform future vaccine design. Caspase-2 cleavage of tau reversibly impairs memory   pp1268 - 1276 Xiaohui Zhao, Linda A Kotilinek, Benjamin Smith, Chris Hlynialuk, Kathleen Zahs et al. doi:10.1038/nm.4199 Caspase-2-mediated cleavage of tau is shown to generate a fibrillation-resistant truncation product (δtau314) that contributes to the missorting of tau into dendritic spines, synaptic dysfunction, neurodegeneration and cognitive impairments in mice. See also: News and Views by Troy & Shelanski Translocation and dissemination of commensal bacteria in post-stroke infection   pp1277 - 1284 Dragana Stanley, Linda J Mason, Kate E Mackin, Yogitha N Srikhanta, Dena Lyras et al. doi:10.1038/nm.4194 In humans and rodent models, commensal gut bacteria contribute to post-stroke infection. Experimental stroke in rodents causes gut barrier dysfunction and permeability, enabling translocation and dissemination of host gut microbiota. Hyaluronan and TLR4 promote surfactant-protein-C-positive alveolar progenitor cell renewal and prevent severe pulmonary fibrosis in mice   pp1285 - 1293 Jiurong Liang, Yanli Zhang, Ting Xie, Ningshan Liu, Huaiyong Chen et al. doi:10.1038/nm.4192 Reduced hyaluronan-TLR4 signaling in a stem cell population of the lung contributes to a lack of renewal of these cells and promotes fibrosis in patients with idiopathic pulmonary fibrosis. See also: News and Views by Mercer & Chambers Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases   pp1294 - 1302 Sophia Frentzas, Eve Simoneau, Victoria L Bridgeman, Peter B Vermeulen, Shane Foo et al. doi:10.1038/nm.4197 Poor responses of liver metastases to the anti-angiogenic agent bevacizumab in patients with colorectal and breast cancer correlate with tumor co-option of pre-existing blood vessels, a mechanism of tumor resistance that might be targeted by the inhibition of cancer cell motility. See also: News and Views by Emblem & Jain PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer   pp1303 - 1313 Fara Braso-Maristany, Simone Filosto, Steven Catchpole, Rebecca Marlow, Jelmar Quist et al. doi:10.1038/nm.4198 In triple-negative breast cancer, the kinase PIM1, which is highly expressed, functions through the transcription factor c-MYC to promote tumor cell survival and growth. See also: Letter by Horiuchi et al. Advertisement An online-only, open access journal publishing high-quality research on ways to help the human body repair, replace and regenerate damaged tissues and organs. Read the latest featured article:  Extracellular Hsp60 triggers tissue regeneration and wound healing by regulating inflammation and cell proliferation    Letters Top Recurrent MET fusion genes represent a drug target in pediatric glioblastoma   pp1314 - 1320 Sebastian Bender, Jan Gronych, Hans-Jorg Warnatz, Barbara Hutter, Susanne Grobner et al. doi:10.1038/nm.4204 Whole-genome sequencing identified recurrent fusions involving the MET oncogene, and MET inhibitors suppressed tumor growth in mouse models and in a human patient. PIM1 kinase inhibition as a targeted therapy against triple-negative breast tumors with elevated MYC expression   pp1321 - 1329 Dai Horiuchi, Roman Camarda, Alicia Y Zhou, Christina Yau, Olga Momcilovic et al. doi:10.1038/nm.4213 In triple-negative breast cancer, the PIM1 kinase is highly expressed, acts to promote tumor cell survival and growth, and increases MYC transcriptional activity. See also: Article by Braso-Maristany et al. Dietary zinc alters the microbiota and decreases resistance to Clostridium difficile infection   pp1330 - 1334 Joseph P Zackular, Jessica L Moore, Ashley T Jordan, Lillian J Juttukonda, Michael J Noto et al. doi:10.1038/nm.4174 Dietary zinc supplements are in common use, but their effect on infection is unclear. New findings now show that excess dietary zinc reduces the diversity of the gut microbiota and increases the susceptibility of antibiotic-treated mice to Clostridium difficile infection. Dual effects of carbon monoxide on pericytes and neurogenesis in traumatic brain injury   pp1335 - 1341 Yoon Kyung Choi, Takakuni Maki, Emiri T Mandeville, Seong-Ho Koh, Kazuhide Hayakawa et al. doi:10.1038/nm.4188 In a mouse model of traumatic brain injury, treatment with a carbon-monoxide-releasing molecule is shown to reduce pericyte cell death and promote neurogenesis, leading to an amelioration of neurological deficits. Analysis Top Classification and characterization of microsatellite instability across 18 cancer types   pp1342 - 1350 Ronald J Hause, Colin C Pritchard, Jay Shendure and Stephen J Salipante doi:10.1038/nm.4191 Systematic analysis of more than 5,900 human tumor exomes yields a new genomic classifier of microsatellite instability and insight into its prevalence and biological implications. Technical Reports Top Microenvironment-dependent growth of preneoplastic and malignant plasma cells in humanized mice   pp1351 - 1357 Rituparna Das, Till Strowig, Rakesh Verma, Srinivas Koduru, Anja Hafemann et al. doi:10.1038/nm.4202 In a new mouse model of multiple myeloma, mice expressing the human versions of six proteins important for hematopoietic function were able to support the growth of primary human multiple myeloma xenografts, including both preneoplastic and malignant plasma cells. Efficient derivation of microglia-like cells from human pluripotent stem cells   pp1358 - 1367 Julien Muffat, Yun Li, Bingbing Yuan, Maisam Mitalipova, Attya Omer et al. doi:10.1038/nm.4189 A protocol is developed to enable the differentiation of microglial-like cells from human pluripotent stem cells, which are shown to resemble primary human microglia, integrate into 3D neuronal cultures, and perform phagocytic and injury-response functions. See also: News and Views by Hammond & Stevens Top Advertisement nature.com webcasts Join us for our upcoming webcast with live Q&A: ADVANCES IN PRECISION MEDICINE AND GENOMIC SEQUENCING Presented by BioPharma Dealmakers Date: Tuesday, November 29 2016 Time: 8AM PST, 11AM EST, 4PM GMT, 5PM CET  REGISTER FOR FREE Sponsored by: Aperiomics Inc. | Bluebee | iNanoBio | Becton Dickinson (BD)     Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. 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