Nature Medicine Contents: June 2016 Volume 22 Number 6 pp 569-692

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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 June 2016 Volume 22, Issue 6 News Correspondence News and Views Articles Letters Technical Report Corrigenda Erratum Advertisement nature.com webcasts Nature Publishing Group presents a custom webcast on: The promise of integrated cancer genomic analysis to precision cancer care Date: Thursday June 9, 2016 Time: 8AM PDT, 11AM EDT, 4PM BST, 5PM CEST  Register for the webcast and live Q&A session Sponsored by:  Agilent Technologies Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Subscribe to Nature with our best current personal subscription offer to access a wealth of scientific articles, features and news every week. Personal subscriptions include app, online, digital and print access so you can enjoy Nature anytime, anywhere.   Advertisement BioPharma Dealmakers  A supplement to Nature Biotechnology & Nature Reviews Drug Discovery Sign up to our NEW networking forum to connect with life sciences companies and partnering professionals looking for dealmaking opportunities.  Stay up to date on emerging therapeutic areas  Ask for advice from our editors and experts in the field SIGN UP NOW   Advertisement VIRAL INFECTION AND IMMUNE RESPONSE Presented by: The Wuhan Institute of Virology | Chinese Society for Immunology | Chinese Society for Microbiology | Nature Microbiology October 21-23, 2016 Shangri-la Hotel | Wuhan, China REGISTER NOW!   News Top Delegation paves way for US-Cuba research collaborations   p569 Monica Heger doi:10.1038/nm0616-569 New efforts to design better tools to track autism therapy response   pp570 - 571 Cassandra Willyard doi:10.1038/nm0616-570 News Feature Overtime under the microscope: Universities prep for impact of new labor rule on labs   pp572 - 573 Shraddha Chakradhar doi:10.1038/nm0616-572 News in Brief Biomedical briefing   pp574 - 575 doi:10.1038/nm0616-574 Opinion Use the Bayh-Dole Act to lower drug prices for government healthcare programs   p576 Alfred B Engelberg and Aaron S Kesselheim doi:10.1038/nm0616-576 As drug prices have increased, there is also greater pressure to find ways to ensure access to medicines. An existing provision of the Bayh-Dole Act could help to lower costs for qualifying drugs in federal programs such as Medicare and Medicaid. Correspondence Top Uveal melanoma cells are resistant to EZH2 inhibition regardless of BAP1 status   pp577 - 578 Marie Schoumacher, Stephanie Le Corre, Alexandre Houy, Eskeatnaf Mulugeta, Marc-Henri Stern et al. doi:10.1038/nm.4098 Reply to "Uveal melanoma cells are resistant to EZH2 inhibition regardless of BAP1 status"   pp578 - 579 Lindsay M LaFave, Wendy Beguelin, Richard Koche, Matt Teater, Barbara Spitzer et al. doi:10.1038/nm.4094 News and Views Top HIV-1 immune evasion—a threat to effective vaccines?   pp580 - 581 Morgane Rolland doi:10.1038/nm.4119 A new study of the impact of cytotoxic T lymphocyte (CTL) escape mutations suggests that holes in the host immune repertoire contribute to poor disease outcomes, owing to a gradual deterioration of the host anti-HIV-1 immune response. This should be accounted for in HIV-1 vaccine development strategies. See also: Article by Carlson et al. | Regulating inflammation with microbial metabolites   pp581 - 583 Benjamin J Marsland doi:10.1038/nm.4117 Two new studies in mice show that the gut microbiota produces metabolites from dietary tryptophan that regulate inflammation in the gut and central nervous system. See also: Article by Rothhammer et al. | Article by Lamas et al. | From schizophrenia risk locus to schizophrenia genes   pp583 - 584 Patrick Sleiman and Hakon Hakonarson doi:10.1038/nm.4122 A new study in humans links genetic variants associated with schizophrenia to changes in the expression of two genes, arsenite methyltransferase (AS3MT) and BLOC-1 related complex subunit 7 (BORCS7). Subsequent investigations provide compelling evidence that AS3MT is involved in the etiology of schizophrenia. See also: Article by Li et al. | Fatty acid metabolism—the first trigger for cachexia?   pp584 - 585 David A Sassoon doi:10.1038/nm.4121 A recent study shows that skeletal muscle responds to tumor-secreted factors by undergoing a change in fatty acid metabolism, and that blocking this metabolic response in mice inhibits muscle wasting. See also: Letter by Fukawa et al. | Nature Medicine JOBS of the week Postdoctoral positions in stem cell biology and regenerative medicine University of Southern California Post-doctoral Positions in Skeletal muscle Stem Cells and molecular medicine UPEC Postdoctoral Fellowship of Computational Medicine at Harvard Medical School Harvard Medical School Clinical and Biochemical Geneticist Boston Children's Hospital; Harvard Medical School Post-Doctoral Fellow University of Oklahoma Health Sciences Center More Science jobs from Nature Medicine EVENT Computational Biomechanics for Medicine 17.10.16 Athens, Greece More science events from Advertisement Nature Reviews Nephrology: Poster on Hyperphosphataemia in CKD This poster outlines the pathophysiology of hyperphosphataemia in CKD and the potential adverse effects of excess phosphate on the heart, bone and vasculature. Available to download free online Produced with support from: Keryx Biopharmaceuticals, Inc.     Articles Top Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor   pp586 - 597 Veit Rothhammer, Ivan D Mascanfroni, Lukas Bunse, Maisa C Takenaka, Jessica E Kenison et al. doi:10.1038/nm.4106 After upregulation of AHR in astrocytes by type I interferons, commensal-microbe-derived metabolites of dietary tryptophan act on astrocytes to suppress CNS inflammation. See also: News and Views by Marsland | Article by Lamas et al. | CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands   pp598 - 605 Bruno Lamas, Mathias L Richard, Valentin Leducq, Hang-Phuong Pham, Marie-Laure Michel et al. doi:10.1038/nm.4102 Metabolism of tryptophan by the gut microbiota is impaired by deficiencies in CARD9, leading to the worsening of colitis. See also: News and Views by Marsland | Article by Rothhammer et al. | Impact of pre-adapted HIV transmission   pp606 - 613 Jonathan M Carlson, Victor Y Du, Nico Pfeifer, Anju Bansal, Vincent Y F Tan et al. doi:10.1038/nm.4100 Jonathan Carlson and colleagues report that pre-adaptation of HIV to a recipient's major histocompatibility complex class I alleles impairs immune control of the virus. See also: News and Views by Rolland | Protection against malaria at 1 year and immune correlates following PfSPZ vaccination   pp614 - 623 Andrew S Ishizuka, Kirsten E Lyke, Adam DeZure, Andrea A Berry, Thomas L Richie et al. doi:10.1038/nm.4110 Fifty-five percent of individuals vaccinated with an attenuated Plasmodium falciparum sporozoite vaccine remained without parasitemia after controlled human malaria infection one year later; immune correlate analysis in humans and non-human primates suggest a role for liver-resident T cells. The EGFR-specific antibody cetuximab combined with chemotherapy triggers immunogenic cell death   pp624 - 631 Chiara Pozzi, Alessandro Cuomo, Ilaria Spadoni, Elena Magni, Alessio Silvola et al. doi:10.1038/nm.4078 The cancer therapeutic cetuximab blocks EGFR signaling on tumor cells. Pozzi et al. now show that this antibody, when combined with chemotherapy, can also kill colorectal cancer cells by triggering immunogenic cell death. An oncogenic Ezh2 mutation induces tumors through global redistribution of histone 3 lysine 27 trimethylation   pp632 - 640 George P Souroullas, William R Jeck, Joel S Parker, Jeremy M Simon, Jie-Yu Liu et al. doi:10.1038/nm.4092 Conditional expression of the most common somatic gain-of-function Ezh2 mutation in mouse models of melanoma and lymphoma reveals insight into its cooperation with other oncogenic events and its effects on the epigenome. Interictal epileptiform discharges induce hippocampal-cortical coupling in temporal lobe epilepsy   pp641 - 648 Jennifer N Gelinas, Dion Khodagholy, Thomas Thesen, Orrin Devinsky and Gyorgy Buzsaki doi:10.1038/nm.4084 Aberrant coupling between hippocampal interictal discharges and neocortical spindle oscillations triggers the generation of cortical /`down/' states in both a rodent epilepsy model and human patients with focal epilepsy. In rats, this pathological network activity is shown to impair cognitive function. A human-specific AS3MT isoform and BORCS7 are molecular risk factors in the 10q24.32 schizophrenia-associated locus   pp649 - 656 Ming Li, Andrew E Jaffe, Richard E Straub, Ran Tao, Joo Heon Shin et al. doi:10.1038/nm.4096 eQTL analysis of human brain RNA-seq data targeted to genes within the 10q24.32 schizophrenia-associated locus reveals that the risk SNP in this region is selectively associated with expression of BORCS7 and a human-specific isoform of AS3MT across multiple independent samples. Expression of only the associated AS3MT isoform is higher in tissue from humans with schizophrenia than in healthy controls. See also: News and Views by Sleiman & Hakonarson | Activation of the pluripotency factor OCT4 in smooth muscle cells is atheroprotective   pp657 - 665 Olga A Cherepanova, Delphine Gomez, Laura S Shankman, Pamela Swiatlowska, Jason Williams et al. doi:10.1038/nm.4109 The pluripotency factor OCT4 is expressed in smooth muscle cells of atherosclerotic lesions in both mice and humans, and has atheroprotective effects in mice. Advertisement   Nature Outlook: Research commercialization Universities need to deliver more value for research outlay. Companies are facing competition in the search for the next business-sustaining product. These sectors have their own objectives, but are locked in a synergistic embrace that is fuelling a push to extract commercial value from academic research. Available free online     Letters Top Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia   pp666 - 671 Tomoya Fukawa, Benjamin Chua Yan-Jiang, Jason Chua Min-Wen, Elwin Tan Jun-Hao, Dan Huang et al. doi:10.1038/nm.4093 Cachexia-inducing tumors release complex factors that promote the increased uptake and burning of fats by muscle, resulting in muscle atrophy—a process that can be blocked if fatty acid oxidation is pharmacologically inhibited. See also: News and Views by Sassoon | Modulation of splicing catalysis for therapeutic targeting of leukemia with mutations in genes encoding spliceosomal proteins   pp672 - 678 Stanley Chun-Wei Lee, Heidi Dvinge, Eunhee Kim, Hana Cho, Jean-Baptiste Micol et al. doi:10.1038/nm.4097 Leukemias bearing heterozygous mutations in the SRSF2 splicing-factor-encoding gene can be therapeutically targeted by pharmacologic inhibition of residual spliceosome function. Two FOXP3+CD4+ T cell subpopulations distinctly control the prognosis of colorectal cancers   pp679 - 684 Takuro Saito, Hiroyoshi Nishikawa, Hisashi Wada, Yuji Nagano, Daisuke Sugiyama et al. doi:10.1038/nm.4086 CD4+ T cells that express the forkhead box P3 (FOXP3) transcription factor function as regulatory T (Treg) cells and hinder effective immune responses against cancer cells. Abundant Treg cell infiltration into tumors is associated with poor clinical outcomes in various types of cancers. However, the role of Treg cells is controversial in colorectal cancers (CRCs), in which FOXP3+ T cell infiltration indicated better prognosis in some studies. Here we show that CRCs, which are commonly infiltrated by suppression-competent FOXP3hi Treg cells, can be classified into two types by the degree of additional infiltration of FOXP3lo nonsuppressive T cells. The latter, which are distinguished from FOXP3+ Treg cells by non-expression of the naive T cell marker CD45RA and instability of FOXP3, secreted inflammatory cytokines. Indeed, CRCs with abundant infiltration of FOXP3lo T cells showed significantly better prognosis than those with predominantly FOXP3hi Treg cell infiltration. Development of such inflammatory FOXP3lo non-Treg cells may depend on secretion of interleukin (IL)-12 and transforming growth factor (TGF)-β by tissues and their presence was correlated with tumor invasion by intestinal bacteria, especially Fusobacterium nucleatum. Thus, functionally distinct subpopulations of tumor-infiltrating FOXP3+ T cells contribute in opposing ways to determining CRC prognosis. Depletion of FOXP3hi Treg cells from tumor tissues, which would augment antitumor immunity, could thus be used as an effective treatment strategy for CRCs and other cancers, whereas strategies that locally increase the population of FOXP3lo non-Treg cells could be used to suppress or prevent tumor formation. Technical Report Top Chromatin immunoprecipitation from fixed clinical tissues reveals tumor-specific enhancer profiles   pp685 - 691 Paloma Cejas, Lewyn Li, Nicholas K O'Neill, Melissa Duarte, Prakash Rao et al. doi:10.1038/nm.4085 Fixed-tissue chromatin immunoprecipitation sequencing (FiT-seq) enables accurate detection of histone marks on chromatin extracted from formalin-fixed paraffin-embedded (FFPE) tissue samples. Corrigenda Top Corrigendum: Retinal lipid and glucose metabolism dictates angiogenesis through the lipid sensor Ffar1   p692 Jean-Sebastien Joyal, Ye Sun, Marin L Gantner, Zhuo Shao, Lucy P Evans et al. doi:10.1038/nm0616-692a Corrigendum: ROR-γ drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer   p692 Junjian Wang, June X Zou, Xiaoqian Xue, Demin Cai, Yan Zhang et al. doi:10.1038/nm0616-692b Corrigendum: Protection against malaria at 1 year and immune correlates following PfSPZ vaccination   p692 Andrew S Ishizuka, Kirsten E Lyke, Adam DeZure, Andrea A Berry, Thomas L Richie et al. doi:10.1038/nm0616-692c Erratum Top Erratum: Modulation of splicing catalysis for therapeutic targeting of leukemia with mutations in genes encoding spliceosomal proteins   p692 Stanley Chun-Wei Lee, Heidi Dvinge, Eunhee Kim, Hana Cho, Jean-Baptiste Micol et al. doi:10.1038/nm0616-692d Top Advertisement Immune Profiling in Health and Disease Presented by: Adaptive Biotechnologies | Nature Immunology | Nature Medicine | Nature Biotechnology | Nature Genetics October 3-5, 2016 | Bell Harbor International Conference Center, Seattle, WA, USA Register now!   Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. 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