Nature Medicine Contents: April 2018 Volume 24 Number 4 pp 375-526

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Advertisement CALL FOR APPLICATIONS: The 2019 Vilcek Prizes for Creative Promise in Biomedical Science Three $50,000 cash awards for young immigrant biomedical scientists. Learn more about the prizes and apply at VILCEK.ORG. DEADLINE: June 11, 2018 TABLE OF CONTENTS April 2018 Volume 24, Issue 4 Editorial News News and Views Review Articles Letters Corrigenda Errata   Advertisement   Countering Antimicrobial Resistance This conference will highlight work on understanding the ecology and spread of infectious agents and innovations in screening, therapeutic modalities and new countermeasures to address the spread of organisms resistant to carbapenem or vancomycin as well as multidrug-resistant Mycobacterium tuberculosis. May 28-29, 2018 | Beijing, China   Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Harrington drug discovery research grants - awards up to $700,000 Harrington Discovery Institute at University Hospitals in Cleveland, Ohio invites Full Applications for the 2019 Harrington Scholar-Innovator Award, offering physician-scientists the resources to advance discoveries into medicines. Full Applications are accepted through May 10, 2018. Apply now at HarringtonDiscovery.org/Grant.     Advertisement Nature Milestone: Anticoagulants from Nature Reviews Cardiology  This Milestone plots the history of anticoagulant drugs, used to prevent and treat thrombotic disorders in millions of patients worldwide. Fourteen Milestone articles are presented on an interactive timeline with associated multimedia.  Access free online >>  Produced with support from:  Portola Pharmaceuticals, Inc.    Advertisement Nature Outlook: Bladder cancer  After three decades without progress, there is now hope that we can move the needle on treating bladder cancer.  Access the free Outlook >>  Produced with support from:  AstraZeneca    Editorial Top A checkup for the flu vaccine   p375 doi:10.1038/nm.4535 Influenza causes almost 650,000 deaths worldwide each year, yet a long-lasting, protective vaccine remains elusive. Global investment—both scientific and financial—in a universal flu vaccine is overdue.   News Top News Features A tale of two diseases: Aging HIV patients inspire a closer look at Alzheimer's disease   pp376 - 377 Shraddha Chakradhar doi:10.1038/nm0418-376   Experimenting with blockchain: Can one technology boost both data integrity and patients' pocketbooks?   pp378 - 381 Katharine Gammon doi:10.1038/nm0418-378   News and Views Top A new site of attack for a malaria vaccine   pp382 - 383 Simon J Draper and Matthew K Higgins doi:10.1038/nm.4533 A newly discovered antibody epitope on the liver-infective form of the parasite that causes malaria opens new doors for vaccine development. See also: Article by Tan et al. | Article by Kisalu et al. | Inflammation weakens HIV prevention   pp384 - 385 Thomas J Hope doi:10.1038/nm.4534 The presence of multiple inflammatory cytokines predicts the failure of a topical 1% tenofovir microbicide gel to protect women against HIV infection. See also: Article by McKinnon et al. | Predicting leukemia relapse   pp385 - 387 Jose Ignacio Martin-Subero doi:10.1038/nm.4529 Mass cytometry of acute B cell lymphoblastic leukemias at diagnosis reveals intrapatient phenotypic heterogeneity and specific signatures that mimic cell developmental stage and predict future relapse. See also: Article by Good et al. | Catalyzing the field of precision oncology, one basket at a time   pp387 - 388 William Pao and Imola Fodor doi:10.1038/nm.4530 A bedside strategy to overcome the limitations of testing in preclinical models and to determine the role of gene mutations and their targetability directly in patients is presented.   Transplanted neural progenitors bridge gaps to benefit cord-injured monkeys   pp388 - 390 Steven A Goldman doi:10.1038/nm.4531 Human neural progenitor cells have been grafted successfully into rhesus monkeys with spinal cord hemisection, resulting in anatomic integration and improved neurological function. See also: Article by Rosenzweig et al. | A molecular mechanism governing memory precision   pp390 - 391 Josue Haubrich and Karim Nader doi:10.1038/nm.4532 A key molecular mechanism has been identified that dictates whether memory will maintain or lose its details over time and that is relevant in post-traumatic stress disorder and dementia. See also: Article by Guo et al. | Nature Medicine JOBS of the week Post-doctoral fellow Washington University School of Medicine, St. Louis Postdoctoral Research Scholar UT Southwestern Medical Center Director, Whitaker Cardiovascular Institute Boston University Executive Director, Brown Center for Immunotherapy Indiana University School of Medicine Postdoctoral Fellow / Pediatrics - 180000006J The University of Tennessee Health Science Center (UTHSC) More Science jobs from Nature Medicine EVENT International Conference on HIV/AIDS Prevention and Control 08.06.18 Colombo, Sri Lanka More science events from Review Top Current understanding of the human microbiome   pp392 - 400 Jack A Gilbert, Martin J Blaser, J Gregory Caporaso, Janet K Jansson, Susan V Lynch et al. doi:10.1038/nm.4517   Advertisement Animation on CRISPR: Gene editing and beyond The CRISPR-Cas9 system has revolutionised gene editing, but cutting DNA isn't all it can do. This Animation, from Nature Methods, explores where CRISPR might be headed next.  Watch the Animation >>  Produced with support from:  Dharmacon    Articles Top A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein   pp401 - 407 Joshua Tan, Brandon K Sack, David Oyen, Isabelle Zenklusen, Luca Piccoli et al. doi:10.1038/nm.4513 Volunteers who develop protection against malaria produce potent antibodies binding to a site of vulnerability on the parasite circumsporozoite protein that is absent in vaccines currently being tested in humans See also: News and Views by Draper & Higgins | Article by Kisalu et al. | A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite   pp408 - 416 Neville K Kisalu, Azza H Idris, Connor Weidle, Yevel Flores-Garcia, Barbara J Flynn et al. doi:10.1038/nm.4512 The identification of antibodies targeting a conserved site of vulnerability in the Plasmodium falciparum circumsporozoite protein reveals opportunities for passive prevention of malaria in vulnerable individuals and provides insights for rational vaccine design. See also: News and Views by Draper & Higgins | Article by Tan et al. | Nociceptor sensory neurons suppress neutrophil and γδ T cell responses in bacterial lung infections and lethal pneumonia   pp417 - 426 Pankaj Baral, Benjamin D Umans, Lu Li, Antonia Wallrapp, Meghna Bist et al. doi:10.1038/nm.4501 Nociceptor sensory neurons suppress innate immunity during bacterial lung infection.   Selective modulation of the androgen receptor AF2 domain rescues degeneration in spinal bulbar muscular atrophy   pp427 - 437 Nisha M Badders, Ane Korff, Helen C Miranda, Pradeep K Vuppala, Rebecca B Smith et al. doi:10.1038/nm.4500 A preclinical therapy to treat neurodegeneration is developed that selectively targets the AF-2 domain of the androgen receptor while sparing other functions of this receptor.   Dentate granule cell recruitment of feedforward inhibition governs engram maintenance and remote memory generalization   pp438 - 449 Nannan Guo, Marta E Soden, Charlotte Herber, Michael TaeWoo Kim, Antoine Besnard et al. doi:10.1038/nm.4491 Dynamic regulation of the cytoskeletal factor ABLIM3 controls the precision of memory representations in rodent models of post-traumatic stress disorder and age-related cognitive impairment. See also: News and Views by Haubrich & Nader | Bone marrow niche trafficking of miR-126 controls the self-renewal of leukemia stem cells in chronic myelogenous leukemia   pp450 - 462 Bin Zhang, Le Xuan Truong Nguyen, Ling Li, Dandan Zhao, Bijender Kumar et al. doi:10.1038/nm.4499 In chronic myelogenous leukemia, leukemia stem cell function requires a microRNA that is provided by bone marrow endothelial cells.   Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling   pp463 - 473 Pernilla Roswall, Matteo Bocci, Michael Bartoschek, Hong Li, Glen Kristiansen et al. doi:10.1038/nm.4494 Paracrine signaling networks in the breast cancer microenvironment uncover determinants of hormone receptor status and offer opportunities for therapeutic intervention.   Single-cell developmental classification of B cell precursor acute lymphoblastic leukemia at diagnosis reveals predictors of relapse   pp474 - 483 Zinaida Good, Jolanda Sarno, Astraea Jager, Nikolay Samusik, Nima Aghaeepour et al. doi:10.1038/nm.4505 Mass cytometry of diagnostic biopsies from children with B cell precursor acute lymphoblastic leukemia identifies a signaling state that predicts relapse. See also: News and Views by Martin-Subero | Restorative effects of human neural stem cell grafts on the primate spinal cord   pp484 - 490 Ephron S Rosenzweig, John H Brock, Paul Lu, Hiromi Kumamaru, Ernesto A Salegio et al. doi:10.1038/nm.4502 In a nonhuman primate model of spinal cord injury, human neural progenitor cell grafts exhibit long-term survival, differentiation, and anatomical integration with host spinal circuitry. See also: News and Views by Goldman | Genital inflammation undermines the effectiveness of tenofovir gel in preventing HIV acquisition in women   pp491 - 496 Lyle R McKinnon, Lenine J Liebenberg, Nonhlanhla Yende-Zuma, Derseree Archary, Sinaye Ngcapu et al. doi:10.1038/nm.4506 In the absence of genital inflammation, tenofovir gel provides superior prevention against HIV acquisition in women. See also: News and Views by Hope | Advertisement Nature Outlook: The future of medicine  Modern medicine is affording people longer and healthier lives. But researchers want to take improvements in health even further. With advances in gene editing, technology to overcome paralysis and efforts to address high drug costs, the future of medicine is bright.  Get your free access >>  Produced with support from Merck KGaA, Darmstadt, Germany    Letters Top H3B-8800, an orally available small-molecule splicing modulator, induces lethality in spliceosome-mutant cancers   pp497 - 504 Michael Seiler, Akihide Yoshimi, Rachel Darman, Betty Chan, Gregg Keaney et al. doi:10.1038/nm.4493 The small molecule H3B-8800 selectively modulates RNA splicing to preferentially kill tumor cells bearing mutations in genes encoding spliceosome components.   Combinatorial inhibition of PTPN12-regulated receptors leads to a broadly effective therapeutic strategy in triple-negative breast cancer   pp505 - 511 Amritha Nair, Hsiang-Ching Chung, Tingting Sun, Siddhartha Tyagi, Lacey E Dobrolecki et al. doi:10.1038/nm.4507 Targeting tyrosine kinase receptors that share the feedback inhibitor PTPN12 leads to broad spectrum therapeutic suppression of triple-negative breast cancer.   SHP2 inhibition restores sensitivity in ALK-rearranged non-small-cell lung cancer resistant to ALK inhibitors   pp512 - 517 Leila Dardaei, Hui Qin Wang, Manrose Singh, Paul Fordjour, Katherine X Shaw et al. doi:10.1038/nm.4497 Genomic and drug screens identify SHP2 blockade as a therapeutic approach for ALK-rearranged non-small cell lung cancers developing resistance through ALK-mutant-independent mechanisms.   Targeting hepatic glutaminase activity to ameliorate hyperglycemia   pp518 - 524 Russell A Miller, Yuji Shi, Wenyun Lu, David A Pirman, Aditi Jatkar et al. doi:10.1038/nm.4514 In mice, elevated glucagon during type 2 diabetes promotes more hepatic glutamine flux and greater gluconeogenesis, while reducing glutamine metabolism in the liver lowers hyperglycemia.   Corrigenda Top Corrigendum: Classification and characterization of microsatellite instability across 18 cancer types   p525 Ronald J Hause, Colin C Pritchard, Jay Shendure and Stephen J Salipante doi:10.1038/nm0418-525a   Corrigendum: Suppression of luteinizing hormone enhances HSC recovery after hematopoietic injury   p525 Enrico Velardi, Jennifer J Tsai, Stefan Radtke, Kirsten Cooper, Kimon V Argyropoulos et al. doi:10.1038/nm0418-525b   Corrigendum: Positively selected enhancer elements endow osteosarcoma cells with metastatic competence   p525 James J Morrow, Ian Bayles, Alister P W Funnell, Tyler E Miller, Alina Saiakhova et al. doi:10.1038/nm0418-525c   Corrigendum: Sex-specific transcriptional signatures in human depression   p525 Benoit Labonte, Olivia Engmann, Immanuel Purushothaman, Caroline Menard, Junshi Wang et al. doi:10.1038/nm0418-525d   Corrigendum: Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed antidiabetic target in mice selected for leanness   p525 Nicholas M Morton, Jasmina Beltram, Roderick N Carter, Zoi Michailidou, Gregor Gorjanc et al. doi:10.1038/nm0418-525e   Corrigendum: Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing   p526 Miguel Crespo, Eduardo Vilar, Su-Yi Tsai, Kyle Chang, Sadaf Amin et al. doi:10.1038/nm0418-526a   Errata Top Erratum: The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions   p526 Hamid Bolouri, Jason E Farrar, Timothy Triche Jr, Rhonda E Ries, Emilia L Lim et al. doi:10.1038/nm0418-526b   Erratum: Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells   p526 Nimitha R Mathew, Francis Baumgartner, Lukas Braun, David O'Sullivan, Simone Thomas et al. doi:10.1038/nm0418-526c   Top Advertisement Focal Point on Japan's Designated National University Initiative Japan's radical new program to boost just a handful of universities has precedents across the world  Access free online   Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. 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