Nature Medicine Contents: September 2012 Volume 18 Number 9 pp 1305-1445

Advertisement Roche's X-tremeGENE Transfection Reagents Transfect efficiently with low cytotoxicity - proven in 275 different cell types...over 130 cancer cells. Free sample and protocols at www.x-tremegene.roche.com For life science research only. Not for use in diagnostic procedures. TABLE OF CONTENTS September 2012 Volume 18, Issue 9 Podcast Editorial News Book Review Correspondence News and Views Community Corner Between Bedside and Bench Research Highlights Articles Letters Technical Report Erratum Corrigenda Subscribe   Facebook   RSS   Recommend to library   Twitter   Podcast Advertisement Nature Outlook: Breast Cancer Each year, 1.3 million women - and some 13,000 men - are diagnosed with breast cancer. The past few decades have seen huge advances in treatment, but about one-quarter of those diagnosed will die from the disease. The difficult challenges are only just starting. Access the Outlook free online for six months. Produced with support from: Saisei Mirai   Advertisement Online-only personal subscriptions now available For only 49 USD/29 GBP/29 EUR to selected journals Subscribe now!   Nature Medicine Podcast  Top Smell test for gene therapy  Gene therapy fixes olfactory function in mice and a computer model helps predict antiviral drug resistance in people. Listen Now Editorial Top The cure conundrum   p1305 doi:10.1038/nm.2951 This summer, researchers launched a strategy to accelerate finding a cure for HIV. The effort aims to revolutionize treatment of the infection, but the inherent risks require that regulators ensure a measured approach. News Top Consumer gene tests poised for regulatory green light   p1306 Asher Mullard doi:10.1038/nm0912-1306 Strapped for funding, medical researchers pitch to the crowd   p1307 Virginia Hughes doi:10.1038/nm0912-1307 Drug pipeline is flush with new options for chronic constipation   pp1308 - 1309 Elie Dolgin doi:10.1038/nm0912-1308 NIH aims to facilitate extramural research through new grants   p1309 Kathleen Raven doi:10.1038/nm0912-1309 Lack of BRCA testing approval creates snag for cancer trials   p1310 Anna Azvolinsky doi:10.1038/nm0912-1310a Correction   p1310 doi:10.1038/nm0912-1310b Controversial egg-producing stem cells promise better IVF   p1311 Elie Dolgin doi:10.1038/nm0912-1311 Drug companies look to biomarkers to salvage cancer target   pp1312 - 1313 Elie Dolgin doi:10.1038/nm0912-1312a Stop-work order creates uncertainty for Ebola drug research   p1312 Kathleen Raven doi:10.1038/nm0912-1312b Institutes experiment with a variety of different appeal processes   p1313 Roxanne Palmer doi:10.1038/nm0912-1313 Exon-skipping drug pulls ahead in muscular dystrophy field   p1314 Alisa Opar doi:10.1038/nm0912-1314 Q&A Straight talk with... Mark Sculpher   p1315 doi:10.1038/nm0912-1315 By 2014, the UK will be changing the way it regulates the price it pays for medicines. The government has embraced an idea known as value-based pricing (VBP), with negotiations on how the system will work due to begin this month. One of the most influential thinkers on the UK’s proposed system is health economist Mark Sculpher, director of the Programme on Economic Evaluation and Health Technology Assessment at the University of York. Kate Ravilious met with Sculpher to discuss the value of VBP. News in Brief Biomedical briefing   pp1316 - 1317 doi:10.1038/nm0912-1316 News Feature Turning a new phage   pp1318 - 1320 Lauren Gravitz doi:10.1038/nm0912-1318 The idea of using bacteria-fighting viruses as a weapon against hard-to-treat infections is making a surprising comeback, but with a twist on how it has been attempted for nearly a century. Researchers and companies are now tweaking and deconstructing these bacteria killers in an effort to develop a new arsenal against antibiotic-resistant superbugs[mdash]one with more potency and a better likelihood of regulatory approval. Lauren Gravitz reports. Opinion (Meta)analyze this: Systematic reviews might lose credibility   p1321 Peter Humaidan and Nikolaos P Polyzos doi:10.1038/nm0912-1321 Doctors and regulatory agencies rely on meta-analyses when setting clinical guidelines and making decisions about drugs. However, as the number of these analyses increases, it's clear that many of them lack robust evidence from randomized trials, which may lead to the adoption of treatment modalities of ambiguous value. Without a more disciplined approach requiring a reasonable minimum amount of data, meta-analyses could lose credibility. Book Review Top AIDS: Back to the beginning   pp1322 - 1323 Nathan Wolfe reviews The Origins of AIDS by Jacques Pepin and Tinderbox: How the West Sparked the AIDS Epidemic and How the World Can Finally Overcome It by Craig Timberg and Daniel Halperin doi:10.1038/nm.2857 Correspondence Top Does a [beta]2-adrenergic receptor-WNK4-Na-Cl co-transporter signal cascade exist in the in vivo kidney?   pp1324 - 1325 Shinichi Uchida, Motoko Chiga, Eisei Sohara, Tatemitsu Rai and Sei Sasaki doi:10.1038/nm.2809 Reply to: Does a [beta]2-adrenergic receptor-WNK4-Na-Cl co-transporter signal cascade exist in the in vivo kidney?   pp1325 - 1327 ShengYu Mu, Tatsuo Shimosawa and Toshiro Fujita doi:10.1038/nm.2939 Technical concerns about immunoprecipitation of methylated fetal DNA for noninvasive trisomy 21 diagnosis   pp1327 - 1328 Yu Kwan Tong, Rossa Wai Kwun Chiu, Kwan Chee Allen Chan, Tak Yeung Leung and Yuk Ming Dennis Lo doi:10.1038/nm.2915 Reply to: Technical concerns about immunoprecipitation of methylated fetal DNA for noninvasive trisomy 21 diagnosis   pp1328 - 1329 Philippos C Patsalis doi:10.1038/nm.2914 News and Views Top Protect thee from the sins of thy fathers?   pp1331 - 1332 Scott L Friedman doi:10.1038/nm.2936 Hepatic fibrosis results from chronic liver injury due to viral infection, metabolic diseases, toxins such as alcohol, or immune attack. Now, a heritable epigenetic determinant of fibrosis has been uncovered, providing evidence that sperm from male rats with liver injury confers reduced fibrosis in their male offspring (pages 1369- 1377). See also: Article by Zeybel et al. The tumor microenvironment controls drug sensitivity   pp1332 - 1334 Arne Ostman doi:10.1038/nm.2938 A better understanding of mechanisms involved in regulation of drug sensitivity is crucial for improved cancer treatment. New studies show that cells of the tumor microenvironment modulate the response of cancer cells to chemotherapy and targeted therapies through production of secreted factors (pages 1359-1368). See also: Article by Sun et al. A ROSy future for metabolic regulation of HSC division   pp1334 - 1336 Hal E Broxmeyer and Charlie Mantel doi:10.1038/nm.2917 Unraveling the intracellular networks that regulate the self-renewal and differentiation of hematopoietic stem cells (HSCs) is crucial to enhancing the efficacy of these therapeutic transplantable cells. A newly discovered pathway links a leukemia tumor suppressor gene with a nutrient sensor to regulate fatty-acid oxidation (FAO) and stem cell division[mdash]information with the potential for modulating hematopoiesis for clinical advantage (pages 1350-1358). See also: Article by Ito et al. Anuclear neutrophils keep hunting   pp1336 - 1338 Andreas Peschel and Dominik Hartl doi:10.1038/nm.2918 Neutrophils release extracellular DNA traps (NETs) to capture and kill pathogens. A recent study shows that live neutrophils are simultaneously able to form NETs while crawling and phagocytosing and can even combat bacteria after loss of their nuclear DNA (pages 1386-1393). See also: Article by Yipp et al. Thinking inside the box: how T cell inhibitory receptors signal   pp1338 - 1339 W Nicholas Haining doi:10.1038/nm.2921 T cells responding to tumor cells and chronic viral pathogens are ineffective because their function is suppressed by inhibitory receptors such as Tim-3. New work identifies the first component of the Tim-3 inhibitory signaling pathway in T cells (pages 1394-1400). See also: Article by Rangachari et al. A sweet spot to control complement-induced inflammation   pp1340 - 1341 Daniel Ricklin, Edimara S Reis and John D Lambris doi:10.1038/nm.2916 Complement is intricately involved in inflammatory processes, yet the mechanisms that modulate the actions of its key mediator C5a are poorly understood. A new study uncovers a molecular partnership between three neutrophil receptors in the recognition of differentially glycated immune complexes and sheds light on regulatory processes in autoimmune and inflammatory disorders (pages 1401-1406). See also: Letter by Karsten et al. Nature Medicine JOBS of the week Senior Scientist Respiratory Therapeutic Area Almirall S.A. Investigator Scientist MRC Postdoc in cell physiology - Erasmus MC Rotterdam Erasmus MC Rotterdam, Department of Neuroscience Postdoctoral Position in Cancer Systems Biology Royal College of Surgeons in Ireland Postdoctoral Research Associate Kansas State University Research Scientist - Nursery and Landscape Horticulture (Trees) Vineland Research and Innovation Centre Computational Biology � Senior Scientist GrassRoots Biotechnology Postdoctoral position University Children's Hospital Zurich Postdoctoral Research Assistant University of Oxford (Department of Physiology, Anatomy and Genetics) Research Associate in Ageing Research Imperial College London More Science jobs from Nature Medicine EVENT Nanoscience and Nanotechnology 2012 01.-04.10.12 Frascati, Italy More science events from Community Corner Top Tracking the insidious course of Alzheimer's disease   pp1342 - 1343 doi:10.1038/nm.2922 Between Bedside and Bench Top The not-so-simple hdl story: Is it time to revise the HDL cholesterol hypothesis?   pp1344 - 1346 Daniel J Rader and Alan R Tall doi:10.1038/nm.2937 Formation of plaques in artery walls, or atherogenesis, is known to lead to cardiovascular disease risk and heart disease. Low-density lipoproteins (LDLs), which deliver cholesterol to inflammatory cells in blood vessels, are linked to disease, which is commonly managed using cholesterol-lowering therapies. Whether increasing levels of high-density lipoproteins (HDLs), which remove cholesterol from the circulation, can be cardioprotective has not been clear, despite early clinical studies showing evidence for a positive effect in cardiovascular disease. In 'Bench to Bedside', Daniel J. Rader and Alan R. Tall discuss how the field should focus on promoting reverse cholesterol transport that would result in cholesterol efflux from macrophages to biliary excretion rather than simply trying to increase HDL cholesterol levels. Understanding how different molecular mechanisms operate in this 'HDL flux hypothesis' will uncover ways to develop HDL-targeted therapeutics that will protect from cardiovascular and heart disease. In 'Bedside to Bench', Jay W. Heinecke peruses clinical studies to propose better and simpler ways to measure reverse cholesterol transport in the clinic. Genetic alterations and factors involved in HDL functionality may be useful for quantifying HDL function and finding effective drugs to lower cardiovascular disease risk. The not-so-simple hdl story: A new era for quantifying HDL and cardiovascular risk?   pp1346 - 1347 Jay W Heinecke doi:10.1038/nm.2930 Research Highlights Top Vaccines: Protection from Nipah | Obesity: Gaining SIRT-ainty | Cancer: Partners in crime | Cancer: Awakening metastasis | Immunology: Tweaking T cell responses | Neuroscience: Disabling axonal degeneration | New from NPG Articles Top A PML-PPAR-[delta] pathway for fatty acid oxidation regulates hematopoietic stem cell maintenance   pp1350 - 1358 Keisuke Ito, Arkaitz Carracedo, Dror Weiss, Fumio Arai, Ugo Ala, David E Avigan, Zachary T Schafer, Ronald M Evans, Toshio Suda, Chih-Hao Lee and Pier Paolo Pandolfi doi:10.1038/nm.2882 Keisuke Ito et al. uncover a new pathway regulating hematopoietic stem cell maintenance and function. In this pathway, the promyelocytic leukemia protein (PML) regulates the activity of the PPAR-[delta] nuclear hormone receptor and, thereby, fatty acid oxidation, such that PPAR-[delta] activators have the potential of improving stem cell function. Intriguingly, this pathway controls the cell fate of dividing stem cells. See also: News and Views by Broxmeyer & Mantel Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B   pp1359 - 1368 Yu Sun, Judith Campisi, Celestia Higano, Tomasz M Beer, Peggy Porter, Ilsa Coleman, Lawrence True and Peter S Nelson doi:10.1038/nm.2890 Responses to anticancer therapy are hampered by several factors, and Peter S. Nelson and colleagues here identify a protective effect of the tumor microenvironment. After cytotoxic chemotherapy, inflammatory NF-[kappa]B signaling activates the secretion of WNT16B, which acts on epithelial cells, promoting their survival and fostering tumor growth in vivo. This pathway is also active in human tumors treated with chemotherapy and illustrates the potential caveats of cyclical therapy and the need to overcome environmental protection to successfully eliminate tumors. See also: News and Views by Ostman Multigenerational epigenetic adaptation of the hepatic wound-healing response   pp1369 - 1377 Mujdat Zeybel, Timothy Hardy, Yi K Wong, John C Mathers, Christopher R Fox, Agata Gackowska, Fiona Oakley, Alastair D Burt, Caroline L Wilson, Quentin M Anstee, Matt J Barter, Steven Masson, Ahmed M Elsharkawy, Derek A Mann and Jelena Mann doi:10.1038/nm.2893 Derek Mann and his colleagues have found that experimental induction of liver fibrosis in male rats results in an epigenetic modification of the chromatin in their sperm such that their offspring have a more mild wound-healing response to hepatic fibrogenic insults. The mechanism responsible for this phenomenon is not clear, but it seems to involve a yet unidentified soluble factor released by myofibroblasts that act on either the germ cells or mature sperm. See also: Between Bedside and Bench by Heinecke Antiretroviral dynamics determines HIV evolution and predicts therapy outcome   pp1378 - 1385 Daniel I S Rosenbloom, Alison L Hill, S Alireza Rabi, Robert F Siliciano and Martin A Nowak doi:10.1038/nm.2892 Highly active antiretroviral therapy is crucial to controlling the progression of HIV infection. Therapy failure is often[mdash]but not always[mdash]attributed to resistance mutations in the HIV-1-encoded protein targets. Here Rosenbloom et al. use mathematical modeling to explain the distinct patterns of resistance found with different classes of antiretroviral drugs and predict specific single-pill combination therapies that might prevent resistance even in the setting of poor patient adherence. Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo    pp1386 - 1393 Bryan G Yipp, Bjorn Petri, Davide Salina, Craig N Jenne, Brittney N V Scott, Lori D Zbytnuik, Keir Pittman, Muhammad Asaduzzaman, Kaiyu Wu, H Christopher Meijndert, Stephen E Malawista, Anne de Boisfleury Chevance, Kunyan Zhang, John Conly and Paul Kubes doi:10.1038/nm.2847 Bacteria can be trapped by neutrophil extracellular traps (NETs) in vitro, but their relevance in vivo is uncertain, in part because NETs are thought to be released by dying neutrophils, thereby eliminating the other antimicrobial functions of these cells. Paul Kubes and his colleagues report in this issue that NET release need not kill neutrophils and that NETosis can by dynamically imaged in vivo. See also: News and Views by Peschel & Hartl Bat3 promotes T cell responses and autoimmunity by repressing Tim-3-mediated cell death and exhaustion   pp1394 - 1400 Manu Rangachari, Chen Zhu, Kaori Sakuishi, Sheng Xiao, Jozsef Karman, Andrew Chen, Mathieu Angin, Andrew Wakeham, Edward A Greenfield, Raymond A Sobel, Hitoshi Okada, Peter J McKinnon, Tak W Mak, Marylyn M Addo, Ana C Anderson and Vijay K Kuchroo doi:10.1038/nm.2871 T cell immunoglobulin and mucin domain-containing 3 (Tim-3) is an inhibitory receptor that is expressed on exhausted T cells and suppresses T helper type 1 (TH1) responses. Vijay Kuchroo and his colleagues show that human leukocyte antigen B (HLA-B)-associated transcript 3 (Bat3) binds intracellularly to Tim-3 and represses its function. Bat3 knockdown suppresses the development of experimental autoimmune encephalomyelitis and induces an exhaustion-like phenotype in T cells. See also: News and Views by Haining Letters Top Anti-inflammatory activity of IgG1 mediated by Fc galactosylation and association of Fc[gamma]RIIB and dectin-1   pp1401 - 1406 Christian M Karsten, Manoj K Pandey, Julia Figge, Regina Kilchenstein, Philip R Taylor, Marcela Rosas, Jacqueline U McDonald, Selinda J Orr, Markus Berger, Dominique Petzold, Veronique Blanchard, Andre Winkler, Constanze Hess, Delyth M Reid, Irina V Majoul, Richard T Strait, Nathaniel L Harris, Gabriele Kohl, Eva Wex, Ralf Ludwig, Detlef Zillikens, Falk Nimmerjahn, Fred D Finkelman, Gordon D Brown, Marc Ehlers and Jorg Kohl doi:10.1038/nm.2862 Complement components activate and recruit immune cells, promoting host defense and inflammatory disease. Jorg Kohl and his colleagues demonstrate that IgG1 immune complexes inhibit C5a-mediated inflammatory responses and disease. The inhibitory effect of IgG1 immune complexes requires galactosylation of the antibody, binding to the inhibitory IgG receptor Fc[gamma]RIIB and the association of Fc[gamma]RIIB with the C-type lectin-like receptor dectin-1. See also: News and Views by Ricklin et al. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase   pp1407 - 1412 Saswata Talukdar, Da Young Oh, Gautam Bandyopadhyay, Dongmei Li, Jianfeng Xu, Joanne McNelis, Min Lu, Pingping Li, Qingyun Yan, Yimin Zhu, Jachelle Ofrecio, Michael Lin, Martin B Brenner and Jerrold M Olefsky doi:10.1038/nm.2885 Infiltration of various immune cell types into the fat tissue and liver has been implicated in obesity-induced insulin resistance. Jerry Olefsky and his colleagues now show that neutrophils are one of the earliest immune cells to arrive in these tissues, that they release the protease neutrophil elastase and that this enzyme degrades IRS-1, a key member of the insulin signaling pathway. These results show that neutrophils contribute to insulin resistance and how they may do so. Decreased expression of synapse-related genes and loss of synapses in major depressive disorder   pp1413 - 1417 Hyo Jung Kang, Bhavya Voleti, Tibor Hajszan, Grazyna Rajkowska, Craig A Stockmeier, Pawel Licznerski, Ashley Lepack, Mahesh S Majik, Lak Shin Jeong, Mounira Banasr, Hyeon Son and Ronald S Duman doi:10.1038/nm.2886 Ronald Duman and colleagues report that synapse number is reduced in subjects with major depressive disorder. This is associated with decreased expression of synapse-related genes and increased expression of the transcriptional repressor, GATA1. Expression of GATA1 in prefrontal cortex neurons decreases the expression of synapse-related genes, reduces dendrite branching and produces depressive behavior in a rat model of depression. EPHA4 is a disease modifier of amyotrophic lateral sclerosis in animal models and in humans   pp1418 - 1422 Annelies Van Hoecke, Lies Schoonaert, Robin Lemmens, Mieke Timmers, Kim A Staats, Angela S Laird, Elke Peeters, Thomas Philips, An Goris, Benedicte Dubois, Peter M Andersen, Ammar Al-Chalabi, Vincent Thijs, Ann M Turnley, Paul W van Vught, Jan H Veldink, Orla Hardiman, Ludo Van Den Bosch, Paloma Gonzalez-Perez, Philip Van Damme, Robert H Brown Jr, Leonard H van den Berg and Wim Robberecht doi:10.1038/nm.2901 Epha4 is a receptor involved in axonal repulsion. Wim Robberecht and his colleagues report that genetic or pharmacological inhibition of Epha4 is protective in rodent and zebrafish models of amyotrophic lateral sclerosis. In humans, expression of Epha4 inversely correlates with disease onset and survival, and in two patients, mutations in Epha4 are associated with longer survival, suggesting Epha4 may be targeted therapeutically to prevent axonal degeneration. Gene therapy rescues cilia defects and restores olfactory function in a mammalian ciliopathy model   pp1423 - 1428 Jeremy C McIntyre, Erica E Davis, Ariell Joiner, Corey L Williams, I-Chun Tsai, Paul M Jenkins, Dyke P McEwen, Lian Zhang, John Escobado, Sophie Thomas, Katarzyna Szymanska, Colin A Johnson, Philip L Beales, Eric D Green, James C Mullikin, NISC Comparative Sequencing Program, Aniko Sabo, Donna M Muzny, Richard A Gibbs, Tania Attie-Bitach, Bradley K Yoder, Randall R Reed, Nicholas Katsanis and Jeffrey R Martens doi:10.1038/nm.2860 Ciliopathies are caused by alterations in the development and function of cilia. Now Jeffrey Martens and his colleagues demonstrate anatomic and functional rescue of cilia development in mature, differentiated neurons by adenovirus-mediated restoration of expression of the wild-type protein intraflagellar transport protein 88 (Ift88) and show restoration of olfactory function in a mouse model of ciliopathy. A loss-of-function mutation in IFT88 is also identified in individuals with ciliopathies. Direct regulation of blood pressure by smooth muscle cell mineralocorticoid receptors   pp1429 - 1433 Amy McCurley, Paulo W Pires, Shawn B Bender, Mark Aronovitz, Michelle J Zhao, Daniel Metzger, Pierre Chambon, Michael A Hill, Anne M Dorrance, Michael E Mendelsohn and Iris Z Jaffe doi:10.1038/nm.2891 The mineralocorticoid receptor, targeted by drugs commonly used to treat hypertension, is generally thought to contribute to hypertension by altering kidney function. Using mice lacking the mineralocorticoid receptor specifically in smooth muscle cells, Iris Jaffe and her colleagues show that it also controls many aspects of vascular aging, including blood vessel tone, and that these vascular effects contribute to the mineralocorticoid receptor's prohypertensive actions. Technical Report Top On silico peptide microarrays for high-resolution mapping of antibody epitopes and diverse protein-protein interactions   pp1434 - 1440 Jordan V Price, Stephanie Tangsombatvisit, Guangyu Xu, Jiangtao Yu, Dan Levy, Emily C Baechler, Or Gozani, Madoo Varma, Paul J Utz and Chih Long Liu doi:10.1038/nm.2913 Using the semiconductor synthesis technology of maskless photolithography on microprocessor-grade silicon wafers, Jordan Price and colleagues synthesized microarrays containing every possible overlapping peptide in a linear sequence covering the N terminus of human histone H2B, including post-translational modifications. They demonstrated use of the 'on silico' peptide microarrays for the high-resolution mapping (at the single amino acid level) of epitopes targeted by commercially available H2B-specific antibodies and also by autoantibodies in samples from individuals with systemic lupus erythematosus. Erratum Top Vitamin E decreases bone mass by stimulating osteoclast fusion   p1445 Koji Fujita, Makiko Iwasaki, Hiroki Ochi, Toru Fukuda, Chengshan Ma, Takeshi Miyamoto, Kimitaka Takitani, Takako Negishi-Koga, Satoko Sunamura, Tatsuhiko Kodama, Hiroshi Takayanagi, Hiroshi Tamai, Shigeaki Kato, Hiroyuki Arai, Kenichi Shinomiya, Hiroshi Itoh, Atsushi Okawa and Shu Takeda doi:10.1038/nm0912-1445a Corrigenda Top Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer   p1445 Clara Montagut, Alba Dalmases, Beatriz Bellosillo, Marta Crespo, Silvia Pairet, Mar Iglesias, Marta Salido, Manuel Gallen, Scot Marsters, Siao Ping Tsai, Andre Minoche, Seshagiri Somasekar, Sergi Serrano, Heinz Himmelbauer, Joaquim Bellmunt, Ana Rovira, Jeff Settleman, Francesc Bosch and Joan Albanell doi:10.1038/nm0912-1445b Methylglyoxal modification of Nav1.8 facilitates nociceptive neuron firing and causes hyperalgesia in diabetic neuropathy   p1445 Angelika Bierhaus, Thomas Fleming, Stoyan Stoyanov, Andreas Leffler, Alexandru Babes, Cristian Neacsu, Susanne K Sauer, Mirjam Eberhardt, Martina Schnolzer, Felix Lasischka, Winfried L Neuhuber, Tatjana I Kichko, Ilze Konrade, Ralf Elvert, Walter Mier, Valdis Pirags, Ivan K Lukic, Michael Morcos, Thomas Dehmer, Naila Rabbani, Paul J Thornalley, Diane Edelstein, Carla Nau, Josephine Forbes, Per M Humpert, Markus Schwaninger, Dan Ziegler, David M Stern, Mark E Cooper, Uwe Haberkorn, Michael Brownlee, Peter W Reeh and Peter P Nawroth doi:10.1038/nm0912-1445c Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures established tumors   p1445 Timothy Kottke, Fiona Errington, Jose Pulido, Feorillo Galivo, Jill Thompson, Phonphimon Wongthida, Rosa Maria Diaz, Heung Chong, Elizabeth Ilett, John Chester, Hardev Pandha, Kevin Harrington, Peter Selby, Alan Melcher and Richard Vile doi:10.1038/nm0912-1445d Top Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. 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