Nature Medicine Contents: October 2014 Volume 20 Number 10 pp 1079-1217

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TABLE OF CONTENTS October 2014 Volume 20, Issue 10 Editorial News Correction Book Review Correspondence News and Views Between Bedside and Bench Research Highlights Essay Q&A Brief Communication Articles Letters Technical Report Corrigenda Erratum Subscribe   Facebook   RSS   Recommend to library   Twitter   Podcast Advertisement Peer Review and Public Release of PCORI's Research Findings  Help ensure PCORI's research results are sound and broadly available. Provide comment through November 7 on PCORI's proposed peer review process for its primary research. PATIENT-CENTERED RESEARCH INSTITUTE   Advertisement nature.com webcasts Macmillan Science Communication presents a custom webcast on: An integrated OMICs approach to cancer progression Thursday October 23, 8am PDT, 11am EDT, 4pm BST, 5pm CEST  Register for the webcast and live Q and A session Sponsored by:       Editorial Top Take the plunge (for charity)   p1079 doi:10.1038/nm.3723 News Top Ice bucket challenge cash may help derisk ALS drug research   p1080 Manasi Vaidya doi:10.1038/nm1014-1080 Arrests reveal debate about costs and benefits of proton therapy   p1081 Amanda B Keener doi:10.1038/nm1014-1081 New platform for cataloging hundreds of proteins gets test drive   pp1082 - 1083 Kendall Powell doi:10.1038/nm1014-1082 Connectivity webs from HIV sequences could inform counseling   p1083 Amanda B Keener doi:10.1038/nm1014-1083 News in Brief Biomedical briefing   pp1084 - 1085 doi:10.1038/nm1014-1084 Correction Top Corrections   p1085 doi:10.1038/nm1014-1085 News Top News Feature Hopeful act: A rebel transplants organs from HIV-positive donors   pp1086 - 1088 Sara Reardon doi:10.1038/nm1014-1086 Book Review Top The story of the rogue prions   p1089 Claudio Soto reviews Fatal Flaws: How a Misfolded Protein Baffled Scientists and Changed the Way We Look at the Brain by Jay Ingram doi:10.1038/nm.3718 Correspondence Top The BIM deletion polymorphism cannot account for intrinsic TKI resistance of Chinese individuals with chronic myeloid leukemia   p1090 Xue Chen, Hongxing Liu, Haizhou Xing, Hui Sun and Ping Zhu doi:10.1038/nm.3638 Reply: The BIM deletion polymorphism cannot account for intrinsic TKI resistance of Chinese individuals with chronic myeloid leukemia   pp1090 - 1091 S Tiong Ong, Charles T H Chuah, Tun Kiat Ko, Axel M Hillmer and Wan-Teck Lim doi:10.1038/nm.3652 News and Views Top Astrocyte-derived lactosylceramide implicated in multiple sclerosis   pp1092 - 1093 Abdolmohamad Rostami and Bogoljub Ciric doi:10.1038/nm.3719 Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. A new study has shown that the lipid lactosylceramide, produced by astrocytes, contributes to disease progression in a mouse model of MS. See also: Article by Mayo et al. The impact of JAK-STAT signaling on muscle regeneration   pp1094 - 1095 Jason D Doles and Bradley B Olwin doi:10.1038/nm.3720 Altered stem cell homeostasis underlies functional tissue decline during muscle aging and disease progression. Janus kinase-signal transducer and activator of transcription (JAK-STAT) signal transduction is a crucial regulator of muscle regeneration, and targeting this pathway in mice relieves aspects of debilitating muscle wasting. See also: Article by Price et al. | Letter by Tierney et al. Thymocyte transformation enhanced   pp1096 - 1097 Gayle P Pouliot and Alejandro Gutierrez doi:10.1038/nm.3711 A new study identifies recurrent somatic duplications of a NOTCH1-driven enhancer of MYC in human T cell leukemia. This enhancer is required for both normal and malignant T cell development. See also: Article by Herranz et al. Protein breakdown precedes pancreatic tumor development   pp1097 - 1099 Sam R. Holmstrom and Kenneth P. Olive doi:10.1038/nm.3714 A new study shows that plasma levels of branched-chain amino acids are elevated in subjects several years before they are diagnosed with pancreatic cancer. This may reflect breakdown of peripheral protein stores in the early stages of the disease. See also: Letter by Mayers et al. Understanding the role of progranulin in Alzheimer's disease   pp1099 - 1100 Simon D'Alton and Jada Lewis doi:10.1038/nm.3712 Alzheimer's disease is characterized by severe cognitive decline and brain amyloid plaques. A new study in mouse models that develop features of Alzheimer's disease indicates that progranulin may have a role in clearing these plaques. See also: Article by Minami et al. Nature Medicine JOBS of the week postdoctoral fellow Massachusetts General Hospital Postdoctoral Scientist Medical Research Council Multiple 4-year PhD studentships The University of Manchester PhD Position University of Fribourg More Science jobs from Nature Medicine EVENT World CNS Summit 2015: Modeling & Biomarkers 17.02.15 Boston, USA More science events from Between Bedside and Bench Top Genome Editing: A Tool For Research and Therapy: Targeted genome editing hits the clinic   pp1101 - 1103 Angelo Lombardo and Luigi Naldini doi:10.1038/nm.3721 Targeted genome editing by engineered endonucleases allows the precise introduction of gene deletions and substitutions into the target genome. In 'Bench to Bedside', Keith Joung and his colleagues discuss how genome-editing technologies could be applied to engineer disease-associated somatic variation into human cell lines and disease models. This would allow the functional interpretation of such variants, which could then be applied to molecular diagnostics in the clinic. In 'Bedside to Bench', Angelo Lombardo and Luigi Naldini consider the potential applications of genome editing in the clinic, in which engineered endonucleases have been shown to be safe. Endonucleases could replace disease-associated genes with wild-type versions or be used to delete genes encoding receptors essential to viral host entry to prevent infection. Genome Editing: A Tool For Research and Therapy: Towards a functional understanding of variants for molecular diagnostics using genome editing   pp1103 - 1104 Shengdar Q Tsai, A John Iafrate and J Keith Joung doi:10.1038/nm.3722 Research Highlights Top Neurodegeneration: Arresting aggregation | Cancer: Decoding the noncoding | Vaccines: Bacteria improve vaccine responses | Metabolic syndrome: Sweeteners and glucose intolerance Essay Top Balzac's Unknown Masterpiece: spotting the next big thing in art and science   pp1106 - 1111 Joseph L Goldstein doi:10.1038/nm.3676 Q&A Top Lasker Award Winner Peter Walter   pp1112 - 1114 doi:10.1038/nm.3683 Peter Walter, Professor at the University of California, San Francisco (UCSF), and Kazutoshi Mori, Professor at Kyoto University, share the 2014 Lasker Basic Medical Research Award for their work that resulted in identification of key components of the unfolded protein response (UPR). Walter identified the IRE1 component of the UPR in 1993, shortly after starting his laboratory at UCSF. Lasker Award Winner Kazutoshi Mori   pp1115 - 1117 doi:10.1038/nm.3682 Kazutoshi Mori, Professor at Kyoto University, shares the 2014 Lasker Basic Medical Research Award with Peter Walter, Professor at the University of California, San Francisco. Walter and Mori are honored for their work identifying core components of the unfolded protein response (UPR). Mori made his first major discovery in this area[mdash]identification of the IRE1 component of the UPR[mdash]in 1993, while he was a postdoctoral fellow at the University of Texas Southwestern Medical Center. Lasker Award Winner Mahlon DeLong   pp1118 - 1120 doi:10.1038/nm.3687 Mahlon DeLong, Professor at Emory University School of Medicine, shares the 2014 Lasker[sim]DeBakey Clinical Medical Research Award with Alim Louis Benabid, Chairman of the Board at Clinatec Institute in Grenoble, France. DeLong and Benabid are honored for their work that led to the development of deep brain stimulation, a therapy that has helped relieve symptoms in thousands of patients with advanced Parkinson's disease. Lasker Award Winner Alim Louis Benabid   pp1121 - 1123 doi:10.1038/nm.3688 Alim Louis Benabid, Chairman of the Board at Clinatec Institute in Grenoble, France shares the 2014 Lasker[sim]DeBakey Clinical Medical Research Award with Mahlon DeLong, Professor at Emory University School of Medicine. DeLong and Benabid are honored for their work that led to the development of deep brain stimulation, a therapy that has helped relieve symptoms in thousands of patients with advanced Parkinson's disease. Lasker Award Winner Mary-Claire King   pp1124 - 1125 doi:10.1038/nm.3696 Mary-Claire King, American Cancer Society Professor of Medicine and Genome Sciences at the University of Washington, Seattle, is recognized with the 2014 Lasker[sim]Koshland Special Achievement Award for her wide range of contributions to biology and medicine as well as human rights. King's development of mathematical models of genetics and discovery of the role that a single gene locus, BRCA1, has in hereditary breast cancer have had wide influence, and she has worked tirelessly to apply genetics to reunite missing persons, such as the 'lost children' of Argentina, with their families. Brief Communication Top Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge   pp1126 - 1129 Daphne A Stanley, Anna N Honko, Clement Asiedu, John C Trefry, Annie W Lau-Kilby et al. doi:10.1038/nm.3702 A chimpanzee adenovirus-based vaccination approach elicits acute and long-term protection against ebolavirus challenge in nonhuman primates. Articles Top A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia   pp1130 - 1137 Daniel Herranz, Alberto Ambesi-Impiombato, Teresa Palomero, Stephanie A Schnell, Laura Belver et al. doi:10.1038/nm.3665 A long-range MYC enhancer is duplicated in human T-ALL and is required for T cell development and NOTCH1-induced leukemogenesis. See also: News and Views by Pouliot & Gutierrez In vivo RNAi screening identifies a mechanism of sorafenib resistance in liver cancer   pp1138 - 1146 Ramona Rudalska, Daniel Dauch, Thomas Longerich, Katherine McJunkin, Torsten Wuestefeld et al. doi:10.1038/nm.3679 An in vivo RNAi dropout screen identifies Mapk14 as a new mediator of sorafenib resistance in hepatocellular carcinoma, and Mapk14 inhibition both improves sorafenib therapy and restores sensitivity to sorafenib-resistant tumors. Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation   pp1147 - 1156 Lior Mayo, Sunia A Trauger, Manon Blain, Meghan Nadeau, Bonny Patel et al. doi:10.1038/nm.3681 In multiple sclerosis and experimental autoimmune encephalomyelitis, astrocytes produce lactosylceramide, a glycolipid that promotes astrocyte and microglial activation and immune cell infiltration into the CNS. See also: News and Views by Rostami & Ciric Progranulin protects against amyloid [beta] deposition and toxicity in Alzheimer's disease mouse models   pp1157 - 1164 S Sakura Minami, Sang-Won Min, Grietje Krabbe, Chao Wang, Yungui Zhou et al. doi:10.1038/nm.3672 Progranulin overexpression in Alzheimer's disease model mice protects against neuronal loss and enhances cognitive deficits. See also: News and Views by D'Alton & Lewis Subcellular localization of coagulation factor II receptor-like 1 in neurons governs angiogenesis   pp1165 - 1173 Jean-Sebastien Joyal, Satra Nim, Tang Zhu, Nicholas Sitaras, Jose Carlos Rivera et al. doi:10.1038/nm.3669 The G protein-coupled receptor F2rl1 translocates from the plasma membrane to the nucleus of retinal ganglion neurons to control Vegfa expression and retinal angiogenesis. Inhibition of JAK-STAT signaling stimulates adult satellite cell function   pp1174 - 1181 Feodor D Price, Julia von Maltzahn, C Florian Bentzinger, Nicolas A Dumont, Hang Yin et al. doi:10.1038/nm.3655 In two new reports, STAT3 signaling is shown to be increased in adult muscle satellite cells, and its inhibition improves muscle regeneration. See also: News and Views by Doles & Olwin | Letter by Tierney et al. Letters Top STAT3 signaling controls satellite cell expansion and skeletal muscle repair   pp1182 - 1186 Matthew Timothy Tierney, Tufan Aydogdu, David Sala, Barbora Malecova, Sole Gatto et al. doi:10.1038/nm.3656 In two new reports, STAT3 signaling is shown to be increased in adult muscle satellite cells, and its inhibition improves muscle regeneration. See also: Letter by Tierney et al. | News and Views by Doles & Olwin The intracellular Ca2+ channel MCOLN1 is required for sarcolemma repair to prevent muscular dystrophy   pp1187 - 1192 Xiping Cheng, Xiaoli Zhang, Qiong Gao, Mohammad Ali Samie, Marlene Azar et al. doi:10.1038/nm.3611 Genetic deletion of the lysosomal Ca2+ channel MCOLN1 in mice results in muscular dystrophy, implicating this source of calcium in muscle membrane repair. Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development   pp1193 - 1198 Jared R Mayers, Chen Wu, Clary B Clish, Peter Kraft, Margaret E Torrence et al. doi:10.1038/nm.3686 Elevated plasma levels of branched chain amino acids detected prior to pancreatic cancer diagnosis may result from whole body tissue breakdown occurring during the early stages of this disease. See also: News and Views by Holmstrom & Olive A new tumor suppressor role for the Notch pathway in bladder cancer   pp1199 - 1205 Theodoros Rampias, Paraskevi Vgenopoulou, Margaritis Avgeris, Alexander Polyzos, Konstantinos Stravodimos et al. doi:10.1038/nm.3678 Rampias et al. report that inactivating mutations in Notch pathway components are frequent in human bladder cancer and drive bladder tumorigenesis in mice. Interleukin-8 (CXCL8) production is a signatory T cell effector function of human newborn infants   pp1206 - 1210 Deena Gibbons, Paul Fleming, Alex Virasami, Marie-Laure Michel, Neil J Sebire et al. doi:10.1038/nm.3670 Gibbons et al. show that T cells in newborns, previously thought to have a limited ability to fight infection, can produce interleukin-8, an effector of innate immunity. Technical Report Top An extracorporeal blood-cleansing device for sepsis therapy   pp1211 - 1216 Joo H Kang, Michael Super, Chong Wing Yung, Ryan M Cooper, Karel Domansky et al. doi:10.1038/nm.3640 External blood-cleansing device for rapidly removing microorganisms and endotoxins from blood without first needing to identify the source of the infection. Corrigenda Top Corrigendum: Inhibition of JAK-STAT signaling stimulates adult satellite cell function   p1217 Feodor D Price, Julia von Maltzahn, C Florian Bentzinger, Nicolas A Dumont, Hang Yin et al. doi:10.1038/nm1014-1217a Corrigendum: PAI-1 mediates the antiangiogenic and profibrinolytic effects of 16K prolactin   p1217 Khalid Bajou, Stephanie Herkenne, Victor L Thijssen, Salvino D'Amico, Ngoc-Quynh-Nhu Nguyen et al. doi:10.1038/nm1014-1217b Corrigendum: Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells   p1217 Nicola Gagliani, Chiara F Magnani, Samuel Huber, Monica E Gianolini, Mauro Pala et al. doi:10.1038/nm1014-1217c Erratum Top Erratum: ECM stiffness paves the way for tumor cells   p1217 Victoria Seewaldt doi:10.1038/nm1014-1217d Top Advertisement Nature Communications soon to be fully open access   From 20th October Nature Communications, will become fully open access for all new submissions. 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