Nature Medicine Contents: January 2016 Volume 21 Number 1 pp 1-113

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Financial support for publication has been provided by the Bill & Melinda Gates Foundation   TABLE OF CONTENTS January 2016 Volume 22, Issue 1 Editorial News Correspondence News and Views Perspective Articles Letters Analysis Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement npj Vaccines is an online-only, open access, multidisciplinary journal dedicated to publishing cutting-edge research and development on human and veterinary vaccines. npj Vaccines is now open for submissions – explore the benefits of submitting your next manuscript to the journal.    Editorial Top Take the long view   p1 doi:10.1038/nm.4033 Reproducibility projects yield headline-grabbing numbers, not practical steps for minimizing the investment in and publication of irreproducible research. If used inappropriately, these numbers may have unintended consequences. News Top News Features Ideas in movement: The next wave of brain-computer interfaces   pp2 - 5 Katherine Ellen Foley doi:10.1038/nm0116-2 Treating trisomies: Prenatal Down's syndrome therapies explored in mice   pp6 - 7 Bridget M. Kuehn doi:10.1038/nm0116-6 Take two: Combining immunotherapy with epigenetic drugs to tackle cancer   pp8 - 10 Karen Weintraub doi:10.1038/nm0116-8 The road less traveled: Start-ups invest in novel approaches against neurodegeneration   pp11 - 13 Shraddha Chakradhar doi:10.1038/nm0116-11 News in Brief Biomedical briefing   pp14 - 15 doi:10.1038/nm0116-14 Corrections   p15 doi:10.1038/nm0116-15 Correspondence Top Suppressive activity of human regulatory T cells is maintained in the presence of TNF   pp16 - 17 Bruno Zaragoza, Xin Chen, Joost J Oppenheim, Audrey Baeyens, Sylvie Gregoire et al. doi:10.1038/nm.4019 Reply to "Suppressive activity of human regulatory T cells is maintained in the presence of TNF"   pp18 - 19 Hong Nie, Yingxia Zheng, Runsheng Li and Jingwu Zhang doi:10.1038/nm.4018 News and Views Top Targeting a regulator of protein homeostasis in myeloproliferative neoplasms   pp20 - 21 Lindsay M LaFave and Ross L Levine doi:10.1038/nm.4028 A new study demonstrates that dysregulation of proteostasis can be a transforming event in hematopoiesis that could prove to be therapeutically actionable for treatment of myeloproliferative neoplasms. See also: Letter by Osorio et al. Illuminating inflammasome activity in vivo    pp22 - 23 Heather D Hickman doi:10.1038/nm.4026 Sentinel macrophages in the lymph node provide a first line of defense against invading viruses. A new study visualizes inflammasome activation in virally infected nodal macrophages in mice and shows that this activation augments both innate and adaptive immunity. See also: Article by Sagoo et al. Depleting senescent cells to combat aging   pp23 - 24 Hartmut Geiger doi:10.1038/nm.4024 A new study in mice suggests that pharmacologically targeting the apoptosis proteins BCL-2 and BCL-xL can clear senescent cells from bone marrow and ameliorate stem cell function during aging, bringing us a step closer to preventing senescence-associated tissue attrition in the clinic. See also: Letter by Chang et al. Tau toxicity feeds forward in frontotemporal dementia   pp24 - 25 David C Rubinsztein doi:10.1038/nm.4029 A new study shows that aggregated forms of tau that cause frontotemporal dementia impair proteasome activity. Furthermore, proteasome inhibition can be alleviated by a small molecule that leads to proteasome phosphorylation and activation, thereby reducing tau accumulation. See also: Article by Myeku et al. Nature Medicine JOBS of the week Postdoctoral fellow - Genome Informatics and Precision Medicine Rutgers Cancer Institute of New Jersey Assistant Professor, Term Tenure Track Department of Genomic Medicine The University of Texas MD Anderson Cancer Center Senior Research Scientist Biomarkers / Translational Medicine iTeos Therapeutics Assistant / Associate Professor of Medicine / Gastroenterology Stony Brook University Postdoctoral Positions in ?Regenerative Biology and Medicine? m / f Helmholtz Zentrum M?nchen. More Science jobs from Nature Medicine EVENT 2016 Scientific Conference - AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer 16.05.16 Miami, USA More science events from Perspective Top Prospects for gene-engineered T cell immunotherapy for solid cancers   pp26 - 36 Christopher A Klebanoff, Steven A Rosenberg and Nicholas P Restifo doi:10.1038/nm.4015 Prospects for engineered T cell therapy of solid tumors. Advertisement All content now open access including archives! Nature Communications is an open access journal that publishes high-quality research from all areas of the natural sciences. Papers published by the journal represent important advances of significance to specialists within each subject area including the life sciences. Visit the website to explore ALL the content available within your field.   Articles Top PPAR-δ is repressed in Huntington's disease, is required for normal neuronal function and can be targeted therapeutically   pp37 - 45 Audrey S Dickey, Victor V Pineda, Taiji Tsunemi, Patrick P Liu, Helen C Miranda et al. doi:10.1038/nm.4003 PPAR-δ activity is impaired by mutant huntingtin, and a PPAR-δ agonist attenuates disease in a mouse model of Huntington's disease. Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling   pp46 - 53 Natura Myeku, Catherine L Clelland, Sheina Emrani, Nikolay V Kukushkin, Wai Haung Yu et al. doi:10.1038/nm.4011 In a model of tauopathy, tau directly inhibits proteasome activity, and cognitive impairment can be prevented by activation of cAMP-PKA signaling. See also: News and Views by Rubinsztein Parkinson's disease-associated mutant VPS35 causes mitochondrial dysfunction by recycling DLP1 complexes   pp54 - 63 Wenzhang Wang, Xinglong Wang, Hisashi Fujioka, Charles Hoppel, Alan L Whone et al. doi:10.1038/nm.3983 Mutations in VPS35 that are associated with Parkinson's disease increase the interaction of VPS35 with mitochondrial DLP1, leading to removal of the DLP1 complexes and mitochondrial fragmentation. Structural and functional mitochondrial impairments caused by mutant VPS35 are observed in vitro using cultured neurons and fibroblasts from individuals with PD and in vivo in mouse substantia nigra neurons, where they induce neurodegeneration. In vivo imaging of inflammasome activation reveals a subcapsular macrophage burst response that mobilizes innate and adaptive immunity   pp64 - 71 Pervinder Sagoo, Zacarias Garcia, Beatrice Breart, Fabrice Lemaitre, David Michonneau et al. doi:10.1038/nm.4016 Visualization and tracking of inflammasome activity and ASC speck formation in vivo following viral infection. See also: News and Views by Hickman Letters Top Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues   pp72 - 77 Joseph J C Thome, Kara L Bickham, Yoshiaki Ohmura, Masaru Kubota, Nobuhide Matsuoka et al. doi:10.1038/nm.4008 Early life differentiation and regulatory function of human T cells is confined to particular anatomical sites. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice   pp78 - 83 Jianhui Chang, Yingying Wang, Lijian Shao, Remi-Martin Laberge, Marco Demaria et al. doi:10.1038/nm.4010 A small-molecule inducer of apoptosis is able to kill senescent cells in the bone marrow of irradiated or aged mice, thereby improving hematopoietic stem cell function. See also: News and Views by Geiger TCF1 links GIPR signaling to the control of beta cell function and survival   pp84 - 90 Jonathan E Campbell, John R Ussher, Erin E Mulvihill, Jelena Kolic, Laurie L Baggio et al. doi:10.1038/nm.3997 The details of the GIP signaling pathway are murky, but new data identify a downstream pathway involving Tcf7 that regulates beta cell survival and activity. Loss of the proteostasis factor AIRAPL causes myeloid transformation by deregulating IGF-1 signaling   pp91 - 96 Fernando G Osorio, Clara Soria-Valles, Olaya Santiago-Fernandez, Teresa Bernal, Maria Mittelbrunn et al. doi:10.1038/nm.4013 The authors uncover a role for the proteostasis modulator AIRAPL as a tumor suppressor in myeloproliferative malignancies, through its regulation of IGFR stability. The results ascribe a biological function to AIRAPL, and they implicate prosteostatic deregulation as an oncogenic mechanism in myeloid transformation, thus suggesting potential novel therapeutic strategies. See also: News and Views by LaFave & Levine Analysis Top Systematic discovery of complex insertions and deletions in human cancers   pp97 - 104 Kai Ye, Jiayin Wang, Reyka Jayasinghe, Eric-Wubbo Lameijer, Joshua F McMichael et al. doi:10.1038/nm.4002 The authors develop a new method to mine genomic cancer data to uncover complex indels. These simultaneous deletions and insertions have been over-looked by previous sequencing data analysis methods, and the Pindel-C algorithm uncovers new information about their potential contribution to tumorigenesis. Pan-cancer analysis of the extent and consequences of intratumor heterogeneity   pp105 - 113 Noemi Andor, Trevor A Graham, Marnix Jansen, Li C Xia, C Athena Aktipis et al. doi:10.1038/nm.3984 The authors analyze the extent of intratumor heterogeneity across 12 tumor types to reveal that increased heterogeneity is a general phenomenon and has a biphasic contribution to tumor progression. 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. 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