Nature Medicine Contents: December 2017 Volume 23 Number 12 pp 1385-1499

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Ad close deadline: 4 December, 2017  TABLE OF CONTENTS December 2017 Volume 23, Issue 12 Editorial News Correction Correspondence News and Views Articles Letters Technical Report Corrigenda Advertisement Better Visualize, Analyze, and Phenotype Immune Cells in situ in FFPE Tissue Sections and TMAs Learn how Vectra Polaris™ quantitative pathology imaging system provides unparalleled speed and performance for extracting proteomic and morphometric information from tissue sections.  Download Application Note Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Index 2017 Science Inc.  This supplement investigates the changing role of corporate institutions in the world of science and the costs and benefits to high-quality research of these evolving arrangements.  Read the full supplement >>     Advertisement Nature Outlook: Women’s health  From common diseases that affect the sexes differently to conditions that affect only women — and from birth, through the menopause, to old age — there are many challenges in women’s health. Access the Outlook free online to learn more >> Produced with support from: Symbiomix Therapeutics, LLC   Advertisement Poster on: The expanding CRISPR toolbox  The CRISPR-Cas9 system can do a lot more than gene editing. This Poster, from Nature Methods, explores the newest possibilities of CRISPR.  Available to download free online >>  Produced with support from:  Dharmacon    Editorial Top Cutting out the liver fat   p1385 doi:10.1038/nm.4459 Better animal models of nonalcoholic steatohepatitis are needed to more fully understand the disease and to identify potential new therapeutic treatments for this increasingly common condition. News Top The Yearbook   p1386 Shraddha Chakradhar doi:10.1038/nm1217-1386 From policy advisors who resigned in protest to an agency trying to settle a patent dispute, many of the newsmakers in our 2017 Yearbook made notable decisions. Notable advances 2017   pp1387 - 1389 Tanya Bondar, Javier Carmona, Kate Gao, Brett Benedetti, Michael Basson et al. doi:10.1038/nm1217-1387 This past year included numerous research studies that broke the mold and elucidated new biology and drug targets. Here are some of the exciting papers from 2017 that moved biomedicine forward. Timeline of events   pp1390 - 1391 Shraddha Chakradhar doi:10.1038/nm1217-1390 From a worldwide march in favor of science to an increased focus on diversity and gender equality in the workplace, 2017 was a year that was dominated by activism and social causes. Amidst these events, however, were concerns over unproven treatments and emergency funding. Drugs that made headlines in 2017   pp1392 - 1393 Shraddha Chakradhar doi:10.1038/nm1217-1392 In 2017, cancer drugs once again dominated the news, with many of these medications making headlines for being the first of their kind to gain approval. Beyond cancer, drugs for inflammatory diseases also received attention, for both their successes and their failures. Correction Top Correction   p1391 doi:10.1038/nm1217-1391 Correspondence Top The small molecule CLP257 does not modify activity of the K+-Cl- co-transporter KCC2 but does potentiate GABAA receptor activity   pp1394 - 1396 Ross A Cardarelli, Karen Jones, Lucie I Pisella, Heike J Wobst, Lisa J McWilliams et al. doi:10.1038/nm.4442 Reply to The small molecule CLP257 does not modify activity of the K+-Cl- co-transporter KCC2 but does potentiate GABAA receptor activity   pp1396 - 1398 Martin Gagnon, Marc J Bergeron, Jimena Perez-Sanchez, Isabel Plasencia-Fernandez, Louis-Etienne Lorenzo et al. doi:10.1038/nm.4449 News and Views Top Organoids lead the cancer attack   pp1399 - 1400 Amber R Smith and Calvin J Kuo doi:10.1038/nm.4454 In an article published recently in Nature Medicine, the authors generate organoid models of liver neoplasia. In doing so, they highlight both the diversity of current organoid methodologies and their application to cancer modeling and therapeutics discovery. See also: Article by Hosen et al. Recognition of self-DNA drives cardiac inflammation: why broken hearts fail   pp1400 - 1401 Kory J Lavine and Douglas L Mann doi:10.1038/nm.4455 Signals that govern immune cells in the heart remain poorly defined. A new report in mice shows that pathways involved in sensing viruses orchestrate monocyte and macrophage activation through recognition of DNA derived from dying cardiomyocytes following myocardial infarction. See also: Letter by King et al. Targeted cellular immunotherapy for T cell malignancies   pp1402 - 1403 Teresa Palomero and Adolfo Ferrando doi:10.1038/nm.4458 In a recent study, Maciocia et al. develop a novel T cell receptor beta (TCRB) constant C1-chain-directed cellular immunotherapy for the treatment of T cell malignancies. See also: Article by Maciocia et al. Fattening the role of Ca2+ cycling in adaptive thermogenesis   pp1403 - 1404 Daniel Gamu and A Russell Tupling doi:10.1038/nm.4457 A new study shows that deleting uncoupling protein 1 activates Ca2+ cycling thermogenesis within beige fat, protecting mice against cold-induced hypothermia and dysglycemia following diet-induced obesity. See also: Article by Ikeda et al. Nature Medicine JOBS of the week Principal Scientist in Cellular Pharmacology Johnson & Johnson Research Scientist in Epidemiology Alberta Health Services, Cancer Epidemiology Postdoctoral Fellow in metabolism Massachusetts General Hospital & Harvard Medical School PhD Positions in Cancer Research at the German Cancer Research Center German Cancer Research Center (DKFZ). Tenured Professor Position UNIVERSITY OF ILLINOIS AT CHICAGO- College of Medicine More Science jobs from Nature Medicine EVENT National Family Medicine Board Review 01.03.18 Baltimore, USA More science events from Advertisement Do you have a career question? The Naturejobs podcast features one-on-one Q&As, panel discussions and other exclusive content to help scientists with their careers. Hosted on the Naturejobs blog, the podcast is also available on iTunes and Soundcloud.  Listen today!    Articles Top ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ fibrosis   pp1405 - 1415 David Lagares, Parisa Ghassemi-Kakroodi, Caroline Tremblay, Alba Santos, Clemens K Probst et al. doi:10.1038/nm.4419 TGF-[beta] induces expression of ADAM10, which results in greater shedding of ephrin-B2. This shedding promotes the chemotaxis and activation of myofibroblasts and thus the progression of organ fibrosis. Targeting the T cell receptor [beta]-chain constant region for immunotherapy of T cell malignancies   pp1416 - 1423 Paul M Maciocia, Patrycja A Wawrzyniecka, Brian Philip, Ida Ricciardelli, Ayse U Akarca et al. doi:10.1038/nm.4444 Pule and colleagues identify the TCR [beta]-chain constant region as a new target for chimeric antigen receptor (CAR) T cells in treatment of T cell cancers while potentially preserving a healthy T cell repertoire. They demonstrate that anti-TCRB1 CAR T cells eliminate cancerous TCRB1+ T cells while sparing nearly one-third of normal TCRB2+ T cells. See also: News and Views by Palomero & Ferrando Human primary liver cancer-derived organoid cultures for disease modeling and drug screening   pp1424 - 1435 Laura Broutier, Gianmarco Mastrogiovanni, Monique MA Verstegen, Hayley E Francies, Lena Morrill Gavarro et al. doi:10.1038/nm.4438 Tumor organoids derived from the most common subtypes of primary liver cancer recapitulate the histologic and molecular features of the tissues of origin, even after long-term culture. These in vitro models, as well as those for colorectal cancer reported in Crespo et al. in a previous issue, are amenable for drug screening and allow the identification of therapeutic approaches with potential for cancer treatment. The activated conformation of integrin [beta]7 is a novel multiple myeloma-specific target for CAR T cell therapy   pp1436 - 1443 Naoki Hosen, Yukiko Matsunaga, Kana Hasegawa, Hiroshi Matsuno, Yuki Nakamura et al. doi:10.1038/nm.4431 Hosen et al. identify an active conformation of integrin beta-7 as a cancer-associated antigen in multiple myeloma, and engineer a CAR-T cell that shows efficacy against MM in a mouse model. These findings describe the first conformation-specific CAR-T cell and highlight the potential of conformational targets in cancer immunotherapy. See also: News and Views by Smith & Kuo Asprosin is a centrally acting orexigenic hormone   pp1444 - 1453 Clemens Duerrschmid, Yanlin He, Chunmei Wang, Chia Li, Juan C Bournat et al. doi:10.1038/nm.4432 Asprosin, a recently identified secreted hormone from adipose tissue, acts centrally to promote food intake. UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis   pp1454 - 1465 Kenji Ikeda, Qianqian Kang, Takeshi Yoneshiro, Joao Paulo Camporez, Hiroko Maki et al. doi:10.1038/nm.4429 Calcium cycling induced by the SERCA2b-RyR2 pathway in beige fat cells allows for thermogenic activity independent of UCP1. See also: News and Views by Gamu & Tupling Advertisement Nature Outlook: Amyotrophic lateral sclerosis  ALS is mysterious and deadly, but new discoveries and treatments bring hope. Access the Outlook here >> Produced with support from:  Biogen   BrainStorm   Cytokinetics  Funded by a grant from  Mitsubishi Tanabe Pharma America, Inc.    Letters Top A microRNA screen reveals that elevated hepatic ectodysplasin A expression contributes to obesity-induced insulin resistance in skeletal muscle   pp1466 - 1473 Motoharu Awazawa, Paula Gabel, Eva Tsaousidou, Hendrik Nolte, Marcus Kruger et al. doi:10.1038/nm.4420 Screening reveals that obesity induces the expression of liver ectodysplasin A, which acts on the muscle to induce insulin resistance. Selective neuronal lapses precede human cognitive lapses following sleep deprivation   pp1474 - 1480 Yuval Nir, Thomas Andrillon, Amit Marmelshtein, Nanthia Suthana, Chiara Cirelli et al. doi:10.1038/nm.4433 In humans, a full night of sleep deprivation causes attenuated and delayed neuronal responses that correlate with impaired cognitive performance. IRF3 and type I interferons fuel a fatal response to myocardial infarction   pp1481 - 1487 Kevin R King, Aaron D Aguirre, Yu-Xiang Ye, Yuan Sun, Jason D Roh et al. doi:10.1038/nm.4428 The massive cell death that occurs during myocardial infarction releases self-DNA and triggers an interferon response in infiltrating leukocytes via a cGAS-STING-IRF3 pathway. Interference with this response[mdash]either by genetic disruption of the pathway or antibody blockade of the type I interferon receptor[mdash]is beneficial in mice subjected to myocardial infarction. See also: News and Views by Lavine & Mann Technical Report Top Enhancing the precision of genetic lineage tracing using dual recombinases   pp1488 - 1498 Lingjuan He, Yan Li, Yi Li, Wenjuan Pu, Xiuzhen Huang et al. doi:10.1038/nm.4437 Genetic cell-lineage tracing studies in mice are crucial for delineating the contribution of stem and progenitor cells to different cell types, both in disease states and after regenerative therapy. He et al. have developed new genetic lineage-tracing systems that provide more definitive results than the commonly used Cre-based system and show that this new technology can resolve current controversies in the field, as demonstrated by lineage-tracing studies in the heart and liver. Corrigenda Top Corrigendum: Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure   p1499 Stephanus T Malherbe, Shubhada Shenai, Katharina Ronacher, Andre G Loxton, Gregory Dolganov et al. doi:10.1038/nm1217-1499a Corrigendum: ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ fibrosis   p1499 David Lagares, Parisa Ghassemi-Kakroodi, Caroline Tremblay, Alba Santos, Clemens K Probst et al. doi:10.1038/nm1217-1499b Top Advertisement Nature Reviews Collection — The obesity epidemic: molecular and clinical considerations  This collection of articles describes the latest efforts to understand the molecular mechanisms underlying obesity against a complex backdrop of factors that include socioeconomic status, environment and personal behaviour, as well as advances in treatment.  View the collection     Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. 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