Nature Medicine Contents: October 2015 Volume 21 Number 10 pp 1103-1234

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Advertisement Collaborative diagnostic assay development & validation Co-develop your RNA, DNA or protein based diagnostics (ideally in oncology, infectious diseases & pharmacogenomics) or enabling technologies. MRCT is a life science medial research charity committed to improving the odds for patients. Click to learn more TABLE OF CONTENTS October 2015 Volume 21, Issue 10 Editorial News Correspondence News and Views Review Brief Communications Articles Letter Resource Advertisement   De Novo Antibody Sequencing Creative Biolabs presents you De Novo Antibody Sequencing services with 100% accuracy...based on our 'Database Assisted Shotgun Sequencing' (DASS) technology. All species, isotypes and allotypes of antibodies can be sequenced with 100% coverage... Click to learn more. Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Discover the hottest mobile apps in almost every area of clinical medicine! On behalf of Wiley, Nature readers are invited to take advantage of a FREE trial to any participating journal app, for a limited time. Click here to view!   Advertisement Heartburn is a burning chest pain or discomfort that generally occurs after eating. Although a typical symptom of GERD, heartburn can occur in a number of gastroenterological conditions (such as achalasia) or indeed can be 'functional' with no organic cause. Nature Reviews Gastroenterology & Hepatology have published an infographic that provides a snapshot of heartburn, illustrating pathophysiology, insights into associated gastrointestinal conditions and management. Download it for free here.      Editorial Top A closer look at the 21st Century Cures Act   p1103 doi:10.1038/nm.3976 The proposed 21st Century Cures Act is a potential boon to the funding woes faced by the US National Institutes of Health and the Food and Drug Administration. But a careful look at the provisions within the bill is warranted to avoid enacting policies that could undermine the progressive translation of research into clinical products. News Top News Features A dormant danger: New therapies target a ubiquitous pathogen known as cytomegalovirus   pp1104 - 1105 Nala Rogers doi:10.1038/nm1015-1104 MERS vaccines advance, but will humans or camels get the jab?   p1106 Roxanne Khamsi doi:10.1038/nm1015-1106 Chikungunya is moving fast, but so are researchers in the field   p1107 Alan Dove doi:10.1038/nm1015-1107 Bugging out over Chagas: Bioluminescent protozoans and old drugs might help unravel kissing-bug disease   pp1108 - 1110 Nala Rogers doi:10.1038/nm1015-1108 Opinion The Canadian MD/PhD training program needs reinstated support   p1111 Ryan T Lewinson, Craig A Beers, Lauren C Capozzi, Vadim Iablokov, Michael B Keough et al. doi:10.1038/nm1015-1111 The Canadian Institutes of Health Research (CIHR) recently terminated its MD/PhD training program without clear alternative funding in place. This misguided decision must urgently be reversed, as it has the potential to diminish a unique pool of graduates at the forefront of translational research. News in Brief Biomedical briefing   pp1112 - 1113 doi:10.1038/nm1015-1112 Correspondence Top Characterization of extracellular DDX4- or Ddx4-positive ovarian cells   pp1114 - 1116 Silvia F Hernandez, Nima A Vahidi, Solji Park, R Patrick Weitzel, John Tisdale et al. doi:10.1038/nm.3966 Adult human and mouse ovaries lack DDX4-expressing functional oogonial stem cells   pp1116 - 1118 Hua Zhang, Sarita Panula, Sophie Petropoulos, Daniel Edsgard, Kiran Busayavalasa et al. doi:10.1038/nm.3775 Reply to Adult human and mouse ovaries lack DDX4-expressing functional oogonial stem cells   pp1118 - 1121 Dori C Woods and Jonathan L Tilly doi:10.1038/nm.3964 News and Views Top CD47 blockade as another immune checkpoint therapy for cancer   pp1122 - 1123 Robert H Vonderheide doi:10.1038/nm.3965 The role of CD47—often expressed on tumor cells—as a 'don't eat me' signal that inhibits macrophage phagocytosis is well established. But new work reveals a major role for other immune cell types—T cells and dendritic cells—in the anti-tumor effects of therapeutic CD47 blockade. See also: Article by Liu et al. Antigen-presenting cells look within during influenza infection   pp1123 - 1125 Justine D Mintern and Jose A Villadangos doi:10.1038/nm.3971 During viral infections, antigen-presenting cells (APC) have traditionally been thought to recruit and activate CD4+ T cells by presenting fragments of viral proteins captured from the extracellular environment. A new study indicates that the material the APCs need to present is much closer: in fact, APCs need to make it themselves. See also: Article by Miller et al. Remodeling the susceptibility to stress-induced depression   pp1125 - 1126 Farahnaz Sananbenesi and Andre Fischer doi:10.1038/nm.3970 Depression is mechanistically not well understood. A new study investigates the expression of chromatin-remodeling complexes in a mouse model for depression and describes an epigenetic pathway that may explain why some individuals are more susceptible to stress-induced depression than others. See also: Article by Sun et al. A detour in the quest for oogonial stem cells: methods matter   pp1126 - 1127 David F Albertini and Norbert Gleicher doi:10.1038/nm.3969 Several independent groups question the reliability of an antibody-based method that is used to isolate oogonial stem cells from the ovaries of adult humans, nonhuman primates and mice. See also: Correspondence by Hernandez et al. | Correspondence by Zhang et al. Nature Medicine JOBS of the week Tenure-track faculty position in computational biology and precision medicine Cornell University Tenure-track faculty position in computational biology and precision medicine Weill Cornell Medical School Stem Cell and Regenerative Medicine King Abdullah University of Science and Technology (KAUST) Director, National Library of Medicine DHHS/NIH/NLM More Science jobs from Nature Medicine EVENT 20TH World Congress of Aesthetic Medicine 12.11.15 Florida, USA More science events from Review Top Natural and therapy-induced immunosurveillance in breast cancer   pp1128 - 1138 Guido Kroemer, Laura Senovilla, Lorenzo Galluzzi, Fabrice Andre and Laurence Zitvogel doi:10.1038/nm.3944 Kroemer and colleagues discuss evidence supporting the importance of immunosurveillance in natural and therapy-induced killing of breast tumors. Brief Communications Top HIV-1 infections with multiple founders are associated with higher viral loads than infections with single founders   pp1139 - 1141 Holly Janes, Joshua T Herbeck, Sodsai Tovanabutra, Rasmi Thomas, Nicole Frahm et al. doi:10.1038/nm.3932 Morgane Rolland and colleagues report that in HIV infection, a higher diversity of infecting founder viruses is associated with markers of poorer clinical outcome. Clinical translation of a high-performance neural prosthesis   pp1142 - 1145 Vikash Gilja, Chethan Pandarinath, Christine H Blabe, Paul Nuyujukian, John D Simeral et al. doi:10.1038/nm.3953 An intracortical neural prosthetic system developed in animal studies is translated for clinical use in humans with paralysis. Neural control of computer cursor movements achieved with this system represent the highest performance reported to date. Advertisement EPIK™ miRNA Panel Assays for Biomarker Detection  Screening miRNAs by qPCR? Our innovative EPIK™ panel assays offer improved sensitivity, specificity and speed. View Bioline's introduction to EPIK™ Panels   Articles Top ACF chromatin-remodeling complex mediates stress-induced depressive-like behavior   pp1146 - 1153 HaoSheng Sun, Diane M Damez-Werno, Kimberly N Scobie, Ning-Yi Shao, Caroline Dias et al. doi:10.1038/nm.3939 Upregulation of the ATP-dependent ACF chromatin-remodeling complex in the NAc is a necessary and causal component for susceptibility to stress-induced depressive behaviors in mice, and this complex is also shown to be upregulated in the NAc of depressed humans. See also: News and Views by Sananbenesi & Fischer Critical role of acetylation in tau-mediated neurodegeneration and cognitive deficits   pp1154 - 1162 Sang-Won Min, Xu Chen, Tara E Tracy, Yaqiao Li, Yungui Zhou et al. doi:10.1038/nm.3951 Acetylation of tau at K174 is identified in Alzheimer's disease (AD) brain tissue and exacerbates tau-mediated neurodegeneration and memory impairments in mice. Pharmacological inhibition of tau acetylation ameliorates these phenotypes in a mouse model of AD. Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma   pp1163 - 1171 Pawel K Mazur, Alexander Herner, Stephano S Mello, Matthias Wirth, Simone Hausmann et al. doi:10.1038/nm.3952 The bromodomain and extraterminal (BET) inhibitor JQ1 synergizes with the histone deacetylase inhibitor SAHA to suppress tumor growth in mouse models of pancreatic cancer. Minimal PU.1 reduction induces a preleukemic state and promotes development of acute myeloid leukemia   pp1172 - 1181 Britta Will, Thomas O Vogler, Swathi Narayanagari, Boris Bartholdy, Tihomira I Todorova et al. doi:10.1038/nm.3936 Minimal reduction of PU.1 in mice is sufficient to elicit a preleukemic state that, when combined with a DNA mismatch repair defect, results in progression to myelodysplastic syndrome and acute myeloid leukemia. Metabolic reprogramming induces resistance to anti-NOTCH1 therapies in T cell acute lymphoblastic leukemia   pp1182 - 1189 Daniel Herranz, Alberto Ambesi-Impiombato, Jessica Sudderth, Marta Sanchez-Martin, Laura Belver et al. doi:10.1038/nm.3955 In NOTCH-induced T cell acute lymphoblastic leukemia, the resistance to anti-NOTCH therapy conferred by loss of the Pten tumor suppressor is linked to reversal of the effects of NOTCH inhibition on leukemic cell metabolism. Disruption of KMT2D perturbs germinal center B cell development and promotes lymphomagenesis   pp1190 - 1198 Jiyuan Zhang, David Dominguez-Sola, Shafinaz Hussein, Ji-Eun Lee, Antony B Holmes et al. doi:10.1038/nm.3940 Two studies demonstrate that the methyltransferase KMT2D, which is recurrently mutated in several types of human B cell lymphoma, suppresses tumorigenesis by altering the epigenetic landscape of B cells; Kmt2d deletion in mice perturbs normal B cell development. The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development   pp1199 - 1208 Ana Ortega-Molina, Isaac W Boss, Andres Canela, Heng Pan, Yanwen Jiang et al. doi:10.1038/nm.3943 Two studies demonstrate that the methyltransferase KMT2D, which is recurrently mutated in several types of human B cell lymphoma, suppresses tumorigenesis by altering the epigenetic landscape of B cells; Kmt2d deletion in mice perturbs normal B cell development. CD47 blockade triggers T cell-mediated destruction of immunogenic tumors   pp1209 - 1215 Xiaojuan Liu, Yang Pu, Kyle Cron, Liufu Deng, Justin Kline et al. doi:10.1038/nm.3931 Although previous work indicated that the antitumor effects of anti-CD47 require macrophage phagocytosis of tumor cells, new work done in immunocompetent mice bearing syngeneic tumors reveals a key role for dendritic cell cross-priming of CD8+ T cells. See also: News and Views by Vonderheide Endogenous antigen processing drives the primary CD4+ T cell response to influenza   pp1216 - 1222 Michael A Miller, Asha Purnima V Ganesan, Nancy Luckashenak, Mark Mendonca and Laurence C Eisenlohr doi:10.1038/nm.3958 CD4+ T cell responses are classically induced by presentation of exogenous antigens by antigen-presenting cells. Miller et al. now report that endogenous presentation drives most CD4+ T cell responses in influenza-infected mice. See also: News and Views by Mintern & Villadangos Letter Top The association between sterilizing activity and drug distribution into tuberculosis lesions   pp1223 - 1227 Brendan Prideaux, Laura E Via, Matthew D Zimmerman, Seokyong Eum, Jansy Sarathy et al. doi:10.1038/nm.3937 MALDI mass spectrometry shows distinct patterns of drug distribution in tuberculosis lesions in human lungs that provide insight into treatment efficacy. Resource Top Early life dynamics of the human gut virome and bacterial microbiome in infants   pp1228 - 1234 Efrem S Lim, Yanjiao Zhou, Guoyan Zhao, Irma K Bauer, Lindsay Droit et al. doi:10.1038/nm.3950 Colonization of the infant gut by viruses, bacteriophages and bacteria over the first two years of life. Top 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. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com More Nature Events

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