Nature Medicine Contents: November 2015 Volume 21 Number 11 pp 1235-1371

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TABLE OF CONTENTS November 2015 Volume 21, Issue 11 Editorial News News and Views Review Articles Letters Analysis Technical Reports Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Video Nobel laureates in their own words “Are you sitting comfortably? Then let me tell you about my Nobel prize-winning science.” In this series of animations, Nobel prize-winning scientists talk about work, life and discoveries that change the world. Recorded at the 65th Lindau Nobel Laureate Meeting.  Watch the animations free online. Supported by Mars, Incorporated   Editorial Top Sharing data to save lives   p1235 doi:10.1038/nm.3991 Journals can and should ensure that they erect no barriers to fast and wide sharing of critical data during major public health emergencies. But funders and scientists must also play a part. News Top News Features Driving CARs: As 'living drugs', T cell therapies face dose standardization woes   pp1236 - 1238 Shraddha Chakradhar doi:10.1038/nm1115-1236 Delivering the goods: Scientists seek a way to make CRISPR-Cas gene editing more targeted   pp1239 - 1241 Amanda B Keener doi:10.1038/nm1115-1239 Model network: Canadian program aims to generate models for rare disease   pp1242 - 1243 Katherine Ellen Foley doi:10.1038/nm1115-1242 News in Brief Biomedical briefing   pp1244 - 1245 doi:10.1038/nm1115-1244 News and Views Top A pathway to HIV-1 neutralization breadth   pp1246 - 1247 S Abigail Smith and Cynthia A Derdeyn doi:10.1038/nm.3989 Neutralization breadth is thought to be an important feature of an effective vaccine against HIV-1. A study in one individual has now identified the specific viral variant that engaged the necessary antibody precursor, as well as the viral immunotypes that drove neutralization breadth, improving understanding of how to mimic this process with a vaccine. See also: Letter by Bhiman et al. A TGF-[beta] pathway associated with cancer cachexia   pp1248 - 1249 Denis C Guttridge doi:10.1038/nm.3988 Cancer cachexia leads to involuntary weight loss resulting from the atrophy of skeletal muscle and adipose tissues. Now, in metastatic mouse models of cancer, investigators reveal a cross talk pathway between bone and muscle that provides a new understanding of wasting in advanced cancers. See also: Article by Waning et al. Personalizing pancreatic cancer organoids with hPSCs   pp1249 - 1251 H Chuck Zhang and Calvin J Kuo doi:10.1038/nm.3992 A new study using human pluripotent stem cell (hPSC)-derived human pancreatic organoids to model neoplastic transformation and cancer-derived human pancreatic tumor organoids for drug testing provides new personalized approaches to modeling and treating this malignancy. See also: Technical Report by Huang et al. Targeting Toll-like receptors to treat chronic pain   pp1251 - 1252 Cedric Peirs and Rebecca P Seal doi:10.1038/nm.3986 Chronic pain affects millions of people worldwide. A new study presents a promising therapeutic strategy in which Toll-like receptor (TLR) 5 stimulation enables the analgesic compound, QX-314, to specifically enter and silence large fiber sensory neurons, which convey pain in the setting of injury. See also: Letter by Xu et al. Nature Medicine JOBS of the week Tenure-Track Faculty Positions in Genomic Medicine Institute for Genomic Medicine, Columbia University Postdoctoral Associate in Cancer Genomics and Personalized Medicine University of North Carolina at Chapel Hill Tenure-eligible Assistant or Associate Professor in Molecular Medicine University of Arizona Wellcome Trust 4-year PhD Programme in Mathematical Genomics and Medicine Wellcome Trust Sanger Institute Marie Curie 15 PhD Fellowships University of Cambridge More Science jobs from Nature Medicine EVENT NanoEngineering for Medicine and Biology (NEMB) 21.02.16 Houston, USA More science events from Review Top The emerging role of lncRNAs in cancer   pp1253 - 1261 Maite Huarte doi:10.1038/nm.3981 Maite Huarte discusses our current understanding of the impact of long noncoding RNAs on tumor growth and progression, and how this knowledge might be translated into new therapeutic approaches. Advertisement Renova Life Inc. specializes in transgenic rabbits and guinea pigs production via conventional DNA or RNA microinjection, engaged in developing bioreactor systems and/or novel disease models with TELAN and CRISPR-Cas9 editing technologies. For more information, please see  http://www.renovalife.com/transgenic_rabbits.php   Articles Top Excess TGF-[beta] mediates muscle weakness associated with bone metastases in mice   pp1262 - 1271 David L Waning, Khalid S Mohammad, Steven Reiken, Wenjun Xie, Daniel C Andersson et al. doi:10.1038/nm.3961 Metastasis-mediated osteolysis results in excess release of TGF-[beta] that, in turn, leads to muscle weakness. See also: News and Views by Guttridge Hair follicle-derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma   pp1272 - 1279 Takeya Adachi, Tetsuro Kobayashi, Eiji Sugihara, Taketo Yamada, Koichi Ikuta et al. doi:10.1038/nm.3962 Hair follicle-derived cytokines control the tropism and retention of memory T cells in the skin and promote lymphoma. MicroRNA-148a regulates LDL receptor and ABCA1 expression to control circulating lipoprotein levels   pp1280 - 1289 Leigh Goedeke, Noemi Rotllan, Alberto Canfran-Duque, Juan F Aranda, Cristina M Ramirez et al. doi:10.1038/nm.3949 MicroRNA-148a, whose expression is regulated by the transcription factor SREBP1c, controls LDL and HDL metabolism through direct targeting of the genes encoding the LDL receptor and the cholesterol transporter ABCA1. Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis   pp1290 - 1297 Alexandre Wagschal, S Hani Najafi-Shoushtari, Lifeng Wang, Leigh Goedeke, Sumita Sinha et al. doi:10.1038/nm.3980 From a systematic analysis of genome-wide association studies of blood lipid levels, Wagschal et al. identify several miRNAs that target key proteins involved in cholesterol and lipid metabolism, including the LDL receptor and the ABCA1 cholesterol transporter. Cardiac RKIP induces a beneficial [beta]-adrenoceptor-dependent positive inotropy   pp1298 - 1306 Evelyn Schmid, Stefan Neef, Christopher Berlin, Angela Tomasovic, Katrin Kahlert et al. doi:10.1038/nm.3972 Induction of cardiac contractility, although desirable for restoring heart function, often has long-term detrimental effects. From studies on RKIP, an upstream regulator of [beta]-adrenergic receptor signaling, Schmid et al. show that cardiac contractility in mice can be increased in a well-tolerated manner through the balanced activation of the [beta]1 and [beta]2 subtypes of the adrenergic receptor. PAR1 signaling regulates the retention and recruitment of EPCR-expressing bone marrow hematopoietic stem cells   pp1307 - 1317 Shiri Gur Cohen, Tomer Itkin, Sagarika Chakrabarty, Claudine Graf, Orit Kollet et al. doi:10.1038/nm.3960 Factors traditionally associated with coagulation and inflammation, such as thrombin, PAR1, aPC and EPCR, also independently control the nitric oxide production switch in hematopoietic stem cells, thereby regulating EPCR-expressing stem cell adhesion and retention in the bone marrow or recruitment to the blood. High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response   pp1318 - 1325 Hui Gao, Joshua M Korn, Stephane Ferretti, John E Monahan, Youzhen Wang et al. doi:10.1038/nm.3954 The authors implement a collection of patient-derived xenograft tumors to test cancer drug responses. Letters Top Inhibition of mechanical allodynia in neuropathic pain by TLR5-mediated A-fiber blockade   pp1326 - 1331 Zhen-Zhong Xu, Yong Ho Kim, Sangsu Bang, Yi Zhang, Temugin Berta et al. doi:10.1038/nm.3978 Toll-like receptor 5 (TLR5) expression is found to be enriched in mouse dorsal root ganglion (DRG) A-fiber neurons known to mediate mechanical allodynia, a form of chronic neuropathic pain. Selective silencing of both mouse and human DRG A-fiber neurons is achieved by co-application of the TLR5 ligand flagellin and the lidocaine derivative QX-314, which is also sufficient to reverse mechanical allodynia in three different mouse models of chronic neuropathic pain. See also: News and Views by Peirs & Seal Viral variants that initiate and drive maturation of V1V2-directed HIV-1 broadly neutralizing antibodies   pp1332 - 1336 Jinal N Bhiman, Colin Anthony, Nicole A Doria-Rose, Owen Karimanzira, Chaim A Schramm et al. doi:10.1038/nm.3963 Penny Moore and colleagues identify viral variants from an HIV-1 infected individual that drove maturation of the antibody response from an unmutated common ancestor, ultimately resulting in both broadly neutralizing and strain-specific antibody sublineages. See also: News and Views by Smith & Derdeyn Selective inhibition of the p38 alternative activation pathway in infiltrating T cells inhibits pancreatic cancer progression   pp1337 - 1343 Muhammad S Alam, Matthias M Gaida, Frank Bergmann, Felix Lasitschka, Thomas Giese et al. doi:10.1038/nm.3957 Blocking alternative activation of p38 in tumor-infiltrating CD4+ T cells reduces proinflammatory cytokine production and inhibits pancreatic cancer growth in mice. Loss of BAP1 function leads to EZH2-dependent transformation   pp1344 - 1349 Lindsay M LaFave, Wendy Beguelin, Richard Koche, Matt Teater, Barbara Spitzer et al. doi:10.1038/nm.3947 BAP1 regulation of EZH2 provides therapeutic opportunities in cancer. Analysis Top The consensus molecular subtypes of colorectal cancer   pp1350 - 1356 Justin Guinney, Rodrigo Dienstmann, Xin Wang, Aurelien de Reynies, Andreas Schlicker et al. doi:10.1038/nm.3967 An international consortium of colorectal cancer researchers undertakes a large-scale data sharing project to achieve a consensus molecular classification of colorectal cancers. Technical Reports Top CAUSEL: an epigenome- and genome-editing pipeline for establishing function of noncoding GWAS variants   pp1357 - 1363 Sandor Spisak, Kate Lawrenson, Yanfang Fu, Istvan Csabai, Rebecca T Cottman et al. doi:10.1038/nm.3975 A pipeline incorporating genetic fine mapping, epigenome editing, and genome editing enables functional analysis of disease-associated SNPs located in non-protein-coding regions of the genome. Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell- and patient-derived tumor organoids   pp1364 - 1371 Ling Huang, Audrey Holtzinger, Ishaan Jagan, Michael BeGora, Ines Lohse et al. doi:10.1038/nm.3973 Human pluripotent stem cells can be differentiated into exocrine pancreas progenitor organoids, allowing studies of development and pancreatic cancer modeling. See also: News and Views by Zhang & Kuo Top Advertisement Open for Submissions An interdisciplinary journal dedicated to publishing high-quality open research relevant to all aspects of schizophrenia and psychosis. Explore the benefits of submitting your next research article: http://bit.ly/1usUYYO   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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