Nature Medicine Contents: December 2015 Volume 21 Number 12 pp 1400-1520

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TABLE OF CONTENTS December 2015 Volume 21, Issue 12 Focus Editorial News Correspondence News and Views Q&A Perspectives Reviews Articles Letters Resource Advertisement Are you stuck in Drug Discovery? BOC Sciences' ready-to-use Screening Libraries can help. Composed of an assortment of libraries including the FDA-approved drug library, natural product library and anti-cancer compound library. Click here to learn more on how to advance your drug discovery research. Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Malaria Experimental Genetics (8-14 May 2016)  This laboratory-based advanced course will give participants a working knowledge of, and practical experience in, cutting edge Plasmodium experimental genetics techniques, from designing gene targeting vectors to phenotyping the strains produced. Application and bursary deadline: 5 February.   Advertisement Science Masterclass The 2015 meeting between Nobel laureates and young researchers in Lindau, Germany cast a spotlight on super-resolution microscopy, as discussed in depth in this Nature Outlook, as well as fields as diverse as memory formation and the Higgs bosons.  Access the Outlook free online.  Produced with support from: Mars, Incorporated     Focus Top Focus on Aging Focus issue: December 2015 Volume 21 No 12 Contents Editorial Q&A Perspectives Reviews Editorial Top Aging: toward avoiding the inevitable   p1373 doi:10.1038/nm.4009 Aging is receiving more attention as a risk factor for human disease. With the correct modeling of human heterogeneity and consideration of the environmental factors involved in the aging process, we may be able to delay the onset of human disease. News Top News Features Canine clues: Dog genomes explored in effort to bring human cancer to heel   pp1374 - 1375 Nala Rogers doi:10.1038/nm1215-1374 News in Brief Biomedical briefing   pp1376 - 1377 doi:10.1038/nm1215-1376 News Bias against genetic case reports might compromise medicine   p1378 Wudan Yan doi:10.1038/nm1215-1378 News Features The Yearbook   p1379 Shraddha Chakradhar doi:10.1038/nm1215-1379 Our list of newsmakers this year includes some standout personalities, from a price-hiking, former hedge fund manager to a persistent and now-well-recognized immunotherapy advocate. 2015 in Review   pp1380 - 1381 Katherine Ellen Foley doi:10.1038/nm1215-1380 In the past year, we have witnessed a flurry of debates in the biomedical arena, from the uproar surrounding price gouging to the ethical hand-wringing over the use of CRISPR-Cas9 technology for genome editing. Beyond these topics, 2015 also made news with vaccine mandates, epigenetic mapping and even an accidental shipment of anthrax. Drugs that made headlines in 2015   pp1382 - 1383 Shraddha Chakradhar doi:10.1038/nm1215-1382 This year's newsworthy drugs made strides against cancer, heart disease and more. Some drugs made headlines for their inability to succeed in clinical trials, and others are still waiting, stuck in limbo, for a chance to move forward in the pipeline. Here is a look at a few of them. Notable advances 2015   pp1384 - 1386 Randy Levinson, Alison Farrell, Michael Basson, Kevin Da Silva, Victoria Aranda et al. doi:10.1038/nm1215-1384 This year saw a whirlwind of insights gleaned into topics ranging from heart cell proliferation to organoid modeling. Here are a few of the research papers detailing some of these intriguing discoveries. Correspondence Top Considerations regarding the micromagnetic resonance relaxometry technique for rapid label-free malaria diagnosis   p1387 Stephan Karl, Ivo Mueller and Timothy G St Pierre doi:10.1038/nm.3811 Reply to "Considerations regarding the micromagnetic resonance relaxometry technique for rapid label-free malaria diagnosis"   pp1387 - 1389 Jongyoon Han and Weng Kung Peng doi:10.1038/nm.3959 News and Views Top Debugging the host browns the fat   pp1390 - 1391 Beng San Yeoh and Matam Vijay-Kumar doi:10.1038/nm.3999 Microbiota depletion promotes type 2 cytokine signaling and browning in white adipose tissue of mice. See also: Letter by Suarez-Zamorano et al. A new role for dystrophin in muscle stem cells   pp1391 - 1393 Alexandra C Keefe and Gabrielle Kardon doi:10.1038/nm.4006 Duchenne muscular dystrophy (DMD) is a devastating X-linked disease that is characterized by progressive muscle degeneration and caused by mutations in dystrophin. Dystrophin is critical for myofiber structural integrity, but a new study reveals an additional important role for this protein in muscle stem cells. See also: Article by Dumont et al. PARP inhibitors: a treatment option for AML?   pp1393 - 1394 Lan Wang, Pierre-Jacques Hamard and Stephen D Nimer doi:10.1038/nm.4007 A new study provides a rationale for the use of poly (ADP-ribose) polymerase (PARP) inhibitors to trigger irreparable DNA damage as a therapeutic approach in acute myeloid leukemia (AML). It also provides support for combining PARP inhibitors with agents that reduce HOXA9 protein levels. See also: Article by Esposito et al. Nature Medicine JOBS of the week Cancer Evolution, Assistant Professor Temple University Maternal Fetal Medicine / Clinical Geneticist University of California (UCSF) Postdoctoral Researcher Position at Ohio State University College of Medicine and Comprehensive Cancer Center Ohio State University Computational Postdoctoral Associate at the Icahn School of Medicine at Mount Sinai Icahn School of Medicine at Mount Sinai Radcliffe Department of Medicine 4 Year PhD Scholars Programme Radcliffe Department of Medicine, University of Oxford More Science jobs from Nature Medicine EVENT EACR24: ?From Basic Research to Precision Medicine? 09.07.16 Manchester, UK More science events from Q&A Top Translational strategies in aging and age-related disease   pp1395 - 1399 Mary Armanios, Rafael de Cabo, Joan Mannick, Linda Partridge, Jan van Deursen et al. doi:10.1038/nm.4004 Six leaders in aging research discuss how to translate their findings in the field. Perspectives Top Can aging be 'drugged'?   pp1400 - 1405 Celine E Riera and Andrew Dillin doi:10.1038/nm.4005 In this Perspective, the current approaches to drug aging, and how new approaches may be developed in the future are discussed. Proteostasis and aging   pp1406 - 1415 Susmita Kaushik and Ana Maria Cuervo doi:10.1038/nm.4001 In this Perspective, the mechanisms by which proteostasis is coordinated within and between cells is discussed with an emphasis on how these mechanisms are deregulated upon aging. Reviews Top The metabolic regulation of aging   pp1416 - 1423 Toren Finkel doi:10.1038/nm.3998 Toren Finkel reviews how metabolism and aging are connected, and highlights pathways that could be pharmacologically targeted to combat aging and age-related disease. Cellular senescence in aging and age-related disease: from mechanisms to therapy   pp1424 - 1435 Bennett G Childs, Matej Durik, Darren J Baker and Jan M van Deursen doi:10.1038/nm.4000 In this Review, Jan van Deursen and his colleagues discuss the recent progress in understanding the origin and identity of senescent cells in ageing and their contribution to age-related disease, in addition to discussing the potential for targeting these cells to counteract disease. Articles Top Treatment during a vulnerable developmental period rescues a genetic epilepsy   pp1436 - 1444 Stephan Lawrence Marguet, Vu Thao Quyen Le-Schulte, Andrea Merseburg, Axel Neu, Ronny Eichler et al. doi:10.1038/nm.3987 Treatment with the common diuretic bumetanide during a susceptible developmental window prevents epileptogenesis in a mouse model of a genetic epileptic encephalopathy. An AKT3-FOXG1-reelin network underlies defective migration in human focal malformations of cortical development   pp1445 - 1454 Seung Tae Baek, Brett Copeland, Eun-Jin Yun, Seok-Kyu Kwon, Alicia Guemez-Gamboa et al. doi:10.1038/nm.3982 In human FMCD tissue, a small fraction of pS6+ neurons are enriched for somatic activating mutations of the PI3K-AKT-mTOR pathway. Sparse electroporation of the AKT3 mutation into the developing mouse brain causes a reelin-dependent, non-cell autonomous disruption of neuronal migration, leading to impaired cortical lamination and seizure-like epileptiform EEG activity. Dystrophin expression in muscle stem cells regulates their polarity and asymmetric division   pp1455 - 1463 Nicolas A Dumont, Yu Xin Wang, Julia von Maltzahn, Alessandra Pasut, C Florian Bentzinger et al. doi:10.1038/nm.3990 Dystrophin is expressed in muscle stem cells, in which it regulates their cell division and proper repopulation. See also: News and Views by Keefe & Kardon The TAM receptor Mertk protects against neuroinvasive viral infection by maintaining blood-brain barrier integrity   pp1464 - 1472 Jonathan J Miner, Brian P Daniels, Bimmi Shrestha, Jose L Proenca-Modena, Erin D Lew et al. doi:10.1038/nm.3974 Michael Diamond and colleagues report that TAM receptor deficiency exacerbated West Nile Virus infection in mice and increased the permeability of the blood-brain barrier. Targeting megakaryocytic-induced fibrosis in myeloproliferative neoplasms by AURKA inhibition   pp1473 - 1480 Qiang Jeremy Wen, Qiong Yang, Benjamin Goldenson, Sebastien Malinge, Terra Lasho et al. doi:10.1038/nm.3995 An inhibitor of Aurora kinase promotes megakaryocytic differentiation of cells from patients with primary myelofibrosis and shows antifibrotic effects in mouse models of this disease. Synthetic lethal targeting of oncogenic transcription factors in acute leukemia by PARP inhibitors   pp1481 - 1490 Maria Teresa Esposito, Lu Zhao, Tsz Kan Fung, Jayant K Rane, Amanda Wilson et al. doi:10.1038/nm.3993 The authors uncover a therapeutic vulnerability to PARP inhibition of acute myeloid leukemias driven by certain oncogenic fusions, and they unravel the mechanisms by which these cancers rely on DNA damage and repair pathways for growth. See also: News and Views by Wang et al. Letters Top SWI/SNF-mutant cancers depend on catalytic and non-catalytic activity of EZH2   pp1491 - 1496 Kimberly H Kim, Woojin Kim, Thomas P Howard, Francisca Vazquez, Aviad Tsherniak et al. doi:10.1038/nm.3968 The authors identify EZH2 as a general underlying dependency of tumors with mutations in the SWI/SNF chromatin regulator complex, and they show that EZH2's pro-tumorigenic role may be dependent on non-catalytic activities. This may pose new opportunities and challenges for using EZH2 as a cancer therapy target. Microbiota depletion promotes browning of white adipose tissue and reduces obesity   pp1497 - 1501 Nicolas Suarez-Zamorano, Salvatore Fabbiano, Claire Chevalier, Ozren Stojanovic, Didier J Colin et al. doi:10.1038/nm.3994 Browning of white adipose tissue is induced by depletion of the microbiota, improving metabolic disease and reducing obesity. See also: News and Views by Yeoh & Vijay-Kumar MARCH8 inhibits HIV-1 infection by reducing virion incorporation of envelope glycoproteins   pp1502 - 1507 Takuya Tada, Yanzhao Zhang, Takayoshi Koyama, Minoru Tobiume, Yasuko Tsunetsugu-Yokota et al. doi:10.1038/nm.3956 Kenzo Tokunaga and colleagues report that MARCH8 inhibits the incorporation of the HIV-1 envelope glycoprotein into virus particles, thereby reducing viral infectivity. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence   pp1508 - 1513 Vineet D Menachery, Boyd L Yount Jr, Kari Debbink, Sudhakar Agnihothram, Lisa E Gralinski et al. doi:10.1038/nm.3985 Ralph Baric, Vineet Menachery and colleagues characterize a SARS-like coronavirus circulating in Chinese horseshoe bats to determine its potential to infect primary human airway epithelial cells, cause disease in mice and respond to available therapeutics. Resource Top Evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers   pp1514 - 1520 Melissa Q McCreery, Kyle D Halliwill, Douglas Chin, Reyno Delrosario, Gillian Hirst et al. doi:10.1038/nm.3979 Understanding tumor metastasis is crucial to developing more effective cancer therapies. Here McCreery et al. analyzed the mutational profile of metastases from chemically induced skin tumors in mice and found that parallel evolution of synchronously disseminated tumor cells underlies most metastasis. 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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