Nature Medicine Contents: August 2018 Volume 24 Number 8 pp 1081-1292

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Advertisement Focus on Autoimmune Disease from Nature Immunology A series of Reviews specially commissioned by Nature Immunology discuss the genetic, environmental, microbial and cellular factors underpinning autoimmune disease as well as highlight avenues for therapeutic intervention.  Access free online  Produced with support from Janssen Research & Development  TABLE OF CONTENTS August 2018 Volume 24, Issue 8 Editorial News Feature Research Highlights News & Views Perspectives Brief Communications Letters Articles Resources Amendments & Corrections   Advertisement   Nature Conference on Inflammation and Cancer This meeting will bring together a diverse group of researchers from the many interconnected areas of immunology and cancer to discuss how inflammation affects tumour development and metastasis. Presentations will focus on the most recent findings on the tumour-promoting and -suppressing effects of inflammation, the immune tumour environment, and therapeutic approaches. October 23-25, 2018 | Beijing, China  REGISTER NOW >>   Advertisement 2018 longlist - see the full line up  The nominations for the 2018 Nature Research Awards for Inspiring Science and Innovating Science are in.  See who's been long listed here >  In partnership with The Estée Lauder Companies.   Advertisement nature.com webcasts Nature Research Custom presents a webcast on: Molecular imaging reveals ONC201 antitumor efficacy and immune stimulation in cancer models Date: Wednesday, August 15, 2018 Join our live webcast to learn about the benefits of cell culture, xenograft tissue sections and mouse models coupled with imaging in preclinical immuno-oncology trials. This webcast has been produced on behalf of the sponsor who retains sole responsibility for content  Register for FREE  Sponsored by: Perkin Elmer    Editorial   Keep off-target effects in focus    p1081 doi:10.1038/s41591-018-0150-3 News Feature   Discovery cycle    pp1082 - 1085 Shraddha Chakradhar doi:10.1038/s41591-018-0149-9 Pondering privatization    pp1086 - 1087 Katharine Gammon doi:10.1038/s41591-018-0148-x 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!    Research Highlights   Identifying atrial fibrillation    p1088 Hannah Stower doi:10.1038/s41591-018-0151-2 An antiviral for smallpox    p1088 Hannah Stower doi:10.1038/s41591-018-0152-1 A wasted early warning    p1088 Hannah Stower doi:10.1038/s41591-018-0153-0 Predicting preterm birth    p1088 Hannah Stower doi:10.1038/s41591-018-0154-z Cell therapy for spinal cord injury    p1088 Hannah Stower doi:10.1038/s41591-018-0155-y Medicine JOBS of the week Postdoctoral Scholar The University of Iowa Postdoctoral Research Scientist Columbia University Postdoctoral Research Associate - PRA-Immunology National Jewish Health Associate Senior Lecturer (Assistant Professor) in molecular medicine - tenure track University of Gothenburg (GU) Post-doctoral Associate University of Louisville Health Science Center, School of Medicine More Science jobs from Medicine EVENT Big Data and Cancer Precision Medicine 01.10.18 Boston, USA More science events from Advertisement Scientific Reports Editor's choice collection: Machine Learning in Healthcare There is great scope for machine intelligence to bolster human endeavours to improve health and wellbeing. Here is just a small selection of research published in Scientific Reports that has contributed to the rapid progress of this field in the past few years. Access the collection >>>   News & Views   Beta cell preservation in patients with type 1 diabetes    pp1089 - 1090 Tony K. T. Lam & David Z. I. Cherney doi:10.1038/s41591-018-0144-1 The calcium channel blocker verapamil preserves beta cells in a clinical trial of individuals with adult-onset type I diabetes.   Cellular origin of human cardiac macrophage populations    pp1091 - 1092 Freya R. Svedberg & Martin Guilliams doi:10.1038/s41591-018-0143-2 Targeting senescence    pp1092 - 1094 Manuel Serrano & Nir Barzilai doi:10.1038/s41591-018-0141-4 Immunotherapy for glioblastoma: going viral    pp1094 - 1096 J. Bryan Iorgulescu, David A. Reardon, E. Antonio Chiocca & Catherine J. Wu doi:10.1038/s41591-018-0142-3 Intratumoral infusion of a nonpathogenic replication-competent recombinant polio-rhinovirus chimera (PVSRIPO) for recurrent glioblastoma demonstrates safety and promising preliminary treatment responses.   Perspectives   Learning from bacterial competition in the host to develop antimicrobials    pp1097 - 1103 Manuela Raffatellu doi:10.1038/s41591-018-0145-0 The delicate balance of microbial communities is maintained by competitive mechanisms that provide an avenue for new antimicrobial development.   Brief Communications   Miscarriage and stillbirth following maternal Zika virus infection in nonhuman primates    pp1104 - 1107 Dawn M. Dudley, Koen K. Van Rompay, Lark L. Coffey, Amir Ardeshir, Rebekah I. Keesler et al. doi:10.1038/s41591-018-0088-5 Zika virus infection during pregnancy is associated with an increased rate of fetal loss in nonhuman primates, as reported in this multicenter analysis.   Letters   Verapamil and beta cell function in adults with recent-onset type 1 diabetes    pp1108 - 1112 Fernando Ovalle, Tiffany Grimes, Guanlan Xu, Anish J. Patel, Truman B. Grayson et al. doi:10.1038/s41591-018-0089-4 A phase 2 placebo-controlled randomized trial reveals that verapamil promotes beta cell function in adult subjects with recent-onset type 1 diabetes.   Genetic deficiency of indoleamine 2,3-dioxygenase promotes gut microbiota-mediated metabolic health    pp1113 - 1120 Ludivine Laurans, Nicolas Venteclef, Yacine Haddad, Mouna Chajadine, Fawaz Alzaid et al. doi:10.1038/s41591-018-0060-4 Indoleamine 2,3-dioxygenase normally suppresses inflammation, but knockout of its gene is metabolically beneficial as its depletion reshapes the gut microbiota.   Metformin reverses established lung fibrosis in a bleomycin model    pp1121 - 1131 Sunad Rangarajan, Nathaniel B. Bone, Anna A. Zmijewska, Shaoning Jiang, Dae Won Park et al. doi:10.1038/s41591-018-0087-6 Metformin reverses established lung fibrosis in a bleomycin model in mice.   Reducing protein oxidation reverses lung fibrosis    pp1128 - 1135 Vikas Anathy, Karolyn G. Lahue, David G. Chapman, Shi B. Chia, Dylan T. Casey et al. doi:10.1038/s41591-018-0090-y Targeting a post-translational modification of Fas by recombinant Glrx reverses established lung fibrosis in a mouse model of age-related idiopathic pulmonary fibrosis.   Poly(GR) impairs protein translation and stress granule dynamics in C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis    pp1136 - 1142 Yong-Jie Zhang, Tania F. Gendron, Mark T. W. Ebbert, Aliesha D. O’Raw, Mei Yue et al. doi:10.1038/s41591-018-0071-1 ALS/FTD-related C9orf72 dipeptide-repeat proteins inhibit protein translation and impair stress granule dynamics, and they cause motor and cognitive deficits in mice.   Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses    pp1143 - 1150 Israel Cañadas, Rohit Thummalapalli, Jong Wook Kim, Shunsuke Kitajima, Russell William Jenkins et al. doi:10.1038/s41591-018-0116-5 Retroelements located in antisense orientation within interferon-regulated genes are reactivated in a subset of cancer cells and initiate a STING- and MAVS-dependent feed-forward inflammatory loop, driving antitumor immunity and exhaustion.   DPP8/DPP9 inhibitor-induced pyroptosis for treatment of acute myeloid leukemia    pp1151 - 1156 Darren C. Johnson, Cornelius Y. Taabazuing, Marian C. Okondo, Ashley J. Chui, Sahana D. Rao et al. doi:10.1038/s41591-018-0082-y Small-molecule inhibitors of the serine dipeptidases DPP8 and DPP9 block AML progression by promoting CARD8-dependent pyroptosis of leukemic myeloid cells.   Articles   Oncogenic hijacking of the stress response machinery in T cell acute lymphoblastic leukemia    pp1157 - 1166 Nikos Kourtis, Charalampos Lazaris, Kathryn Hockemeyer, Juan Carlos Balandrán, Alejandra R. Jimenez et al. doi:10.1038/s41591-018-0105-8 Oncogenic NOTCH1 controls transcriptional activation of the heat shock response in T cell acute lymphoblastic leukemia and uncovers potential biomarkers of sensitivity to HSP90 inhibition.   Clonal heterogeneity of acute myeloid leukemia treated with the IDH2 inhibitor enasidenib    pp1167 - 1177 Lynn Quek, Muriel D. David, Alison Kennedy, Marlen Metzner, Michael Amatangelo et al. doi:10.1038/s41591-018-0115-6 Mapping of the clonal structure of bone marrow cells in patients with acute myeloid leukemia treated with the IDH2 inhibitor enasidenib reveals heterogeneity in the cellular differentiation response and in mechanisms of relapse.   A natural killer–dendritic cell axis defines checkpoint therapy–responsive tumor microenvironments    pp1178 - 1191 Kevin C. Barry, Joy Hsu, Miranda L. Broz, Francisco J. Cueto, Mikhail Binnewies et al. doi:10.1038/s41591-018-0085-8 Cross-talk between innate immune cells helps to enhance the antitumor T cell response during checkpoint blockade therapy.   Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate    pp1192 - 1203 Lukas Bunse, Stefan Pusch, Theresa Bunse, Felix Sahm, Khwab Sanghvi et al. doi:10.1038/s41591-018-0095-6 An oncometabolite produced by tumor cells acts as a paracrine immunosuppressant dampening antitumor T cell responses in glioma.   Functional diversity and cooperativity between subclonal populations of pediatric glioblastoma and diffuse intrinsic pontine glioma cells    pp1204 - 1215 Mara Vinci, Anna Burford, Valeria Molinari, Ketty Kessler, Sergey Popov et al. doi:10.1038/s41591-018-0086-7 Genomic and functional analysis of intratumor heterogeneity in pediatric glioma uncovers early clonal divergence and stable spontaneous cooperation between subclonal populations throughout tumor evolution.   A high-fidelity Cas9 mutant delivered as a ribonucleoprotein complex enables efficient gene editing in human hematopoietic stem and progenitor cells    pp1216 - 1224 Christopher A. Vakulskas, Daniel P. Dever, Garrett R. Rettig, Rolf Turk, Ashley M. Jacobi et al. doi:10.1038/s41591-018-0137-0 A bacterial screen yields a Cas9 variant that retains high on-target activity when delivered in the RNP format. As proof of principle, this Cas9 variant enables high-level correction of the sickle cell disease mutation in patient-derived HSPCs.   Suppression of detyrosinated microtubules improves cardiomyocyte function in human heart failure    pp1225 - 1233 Christina Yingxian Chen, Matthew A. Caporizzo, Kenneth Bedi, Alexia Vite, Alexey I. Bogush et al. doi:10.1038/s41591-018-0046-2 Post-translational modification of microtubules by detyrosination is prevalent in failing human cardiomyocytes and inhibits cardiomyocyte contraction, suggesting a new therapeutic strategy for improving heart function.   The human heart contains distinct macrophage subsets with divergent origins and functions    pp1234 - 1245 Geetika Bajpai, Caralin Schneider, Nicole Wong, Andrea Bredemeyer, Maarten Hulsmans et al. doi:10.1038/s41591-018-0059-x Study of macrophage heterogeneity in human hearts reveals a subset of inflammatory macrophages that is associated with cardiac dysfunction in patients with heart failure.   Senolytics improve physical function and increase lifespan in old age    pp1246 - 1256 Ming Xu, Tamar Pirtskhalava, Joshua N. Farr, Bettina M. Weigand, Allyson K. Palmer et al. doi:10.1038/s41591-018-0092-9 Transfer of senescent cells into naive, young mice can induce physical dysfunction, and a senolytic can reverse this dysfunction and potently increase lifespan in aged mice.   Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke    pp1257 - 1267 Dhakshin S. Ramanathan, Ling Guo, Tanuj Gulati, Gray Davidson, April K. Hishinuma et al. doi:10.1038/s41591-018-0058-y Recovery of skilled motor function in rodents after stroke correlates with the restoration of low-frequency quasi-oscillatory activity in the motor cortex, and neuromodulatory electrical stimulation targeting this activity can further accelerate recovery.   Anatomical and functional dichotomy of ocular itch and pain    pp1268 - 1276 Cheng-Chiu Huang, Weishan Yang, Changxiong Guo, Haowu Jiang, Fengxian Li et al. doi:10.1038/s41591-018-0083-x A molecularly defined set of sensory fibers expressing MrgprA3 mediate ocular itch via specific anatomical projections to the conjunctiva, which can be targeted therapeutically in rodent models.   Resources   Phenotype molding of stromal cells in the lung tumor microenvironment    pp1277 - 1289 Diether Lambrechts, Els Wauters, Bram Boeckx, Sara Aibar, David Nittner et al. doi:10.1038/s41591-018-0096-5 A comprehensive single-cell analysis of the lung cancer microenvironment reveals marked heterogeneity of transcriptional networks that defines novel clinically relevant stromal cell populations.   Amendments & Corrections   Author Correction: Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes    pp1290 - 1291 Bjoern Chapuy, Chip Stewart, Andrew J. Dunford, Jaegil Kim, Atanas Kamburov et al. doi:10.1038/s41591-018-0097-4 Publisher Correction: Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes    p1292 Bjoern Chapuy, Chip Stewart, Andrew J. Dunford, Jaegil Kim, Atanas Kamburov et al. doi:10.1038/s41591-018-0098-3 Advertisement Nature Briefing is an essential round-up of science news, opinion and analysis, free in your inbox every weekday. With Nature Briefing, we'll keep you updated on the latest research, so you can focus on yours. Click here to sign up.   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. 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