Nature Medicine Contents: November 2014 Volume 20 Number 11 pp 1219-1353

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TABLE OF CONTENTS November 2014 Volume 20, Issue 11 Editorial News Book Review Correspondence News and Views Research Highlights Review Articles Letters Technical Reports Subscribe   Facebook   RSS   Recommend to library   Twitter   Podcast Advertisement Modeling Diseases in Microgravity Identification of animal models and cell-based models for improved understanding of human disease and drug screening on the International Space Station U.S. National Laboratory.   Request for information.   Advertisement A picture of health Reporter Lorna Stewart travels to the German island of Lindau to meet 600 of science’s brightest young minds and 37 rock stars – Nobel laureates. In a series of four films, Stewart asks some of the most profound questions in medicine.  Watch the videos online.  Published weekly from 24th Sep- 15th Oct 2014 Supported by Mars, Incorporated     Editorial Top Course correction   p1219 doi:10.1038/nm.3756 The international response to the ongoing Ebola epidemic has in many respects been more reactive than proactive. But there are changes that, if made, may shift the balance toward future readiness. News Top Tumor sequencing takes off, but insurance reimbursement lags   pp1220 - 1221 Shraddha Chakradhar doi:10.1038/nm1114-1220 News in Brief Biomedical briefing   pp1222 - 1223 doi:10.1038/nm1114-1222 FDA's post-approval studies continue to suffer delays and setbacks   pp1224 - 1225 Cassandra Willyard doi:10.1038/nm1114-1224 As funds to sync health records dwindle, research could suffer   pp1225 - 1226 Manasi Vaidya doi:10.1038/nm1114-1225 Book Review Top Eradicating infectious disease   p1227 William R Jacobs Jr reviews The End of Plagues: The Global Battle Against Infectious Disease by John Rhodes doi:10.1038/nm.3738 Correspondence Top Lrp5 regulation of bone mass and serotonin synthesis in the gut   pp1228 - 1229 Aruna Kode, Arnaud Obri, Riccardo Paone, Stavroula Kousteni, Patricia Ducy et al. doi:10.1038/nm.3698 Reply to Lrp5 regulation of bone mass and gut serotonin synthesis   pp1229 - 1230 Yajun Cui, Paul J Niziolek, Bryan T MacDonald, Natalia Alenina, Susann Matthes et al. doi:10.1038/nm.3697 Colorectal cancer classification based on gene expression is not associated with FOLFIRI response   pp1230 - 1231 Raquel Martinez-Garcia, Pedro P Lopez-Casas, Daniel Rico, Alfonso Valencia and Manuel Hidalgo doi:10.1038/nm.3701 Reply to Colorectal cancer classification based on gene expression is not associated with FOLFIRI response   pp1231 - 1232 Anguraj Sadanandam, Joe Gray and Douglas Hanahan doi:10.1038/nm.3742 News and Views Top Megakaryocytes in the hematopoietic stem cell niche   pp1233 - 1234 Ryan B. Day and Daniel C. Link doi:10.1038/nm.3745 Mesenchymal stromal cells are key components of hematopoietic stem cell (HSC) niches in the bone marrow. Two studies now show that hematopoietic-derived megakaryocytes also contribute to the HSC niche, regulating HSC quiescence and function. See also: Letter by Zhao et al. | Letter by Bruns et al. Fatty acid synthesis tips the TH17-Treg cell balance   pp1235 - 1236 David O'Sullivan and Erika L. Pearce doi:10.1038/nm.3744 A recent study reports that de novo fatty acid synthesis is important for differentiation of T helper 17 (TH17) cells. Suppression of this pathway through inhibition of acetyl-CoA carboxylase (ACC) with soraphen A prevents TH17 cell differentiation and consequently enforces a regulatory T cell phenotype. See also: Letter by Berod et al. Asparagine endopeptidase cleaves tau and promotes neurodegeneration   pp1236 - 1238 Hanna Rosenmann doi:10.1038/nm.3749 Truncation of tau contributes to the formation of neurofibrillary tangles in Alzheimer's disease. A new study finds a direct role for a lysosomal cysteine protease, asparagine endopeptidase, in cleaving tau into neurotoxic fragments. See also: Article by Zhang et al. Osteoclast progenitors promote bone vascularization and osteogenesis   pp1238 - 1240 Anjali P. Kusumbe and Ralf H. Adams doi:10.1038/nm.3747 Preosteoclasts give rise to bone-resorbing osteoclasts, which are crucial for skeletal homeostasis. A study now shows that preosteoclasts also contribute to bone formation by releasing platelet-derived growth factor-BB, which promotes bone vascularization and osteogenesis. See also: Article by Moverare-Skrtic et al. Nature Medicine JOBS of the week Postdoctoral Research Fellow University of Leeds Clinical Research Fellow Imperial College London Postdoctoral Scientist Medical Research Council PhD studentship University of Aberdeen Postdoctoral Felow Oregon Health & Science University (OHSU) Scientific Director Basque Centre for Climate Change Postdoctoral Fellowships The Rockefeller University Research Fellow The University of Nottingham More Science jobs from Nature Medicine EVENT 7th Ocular Diseases Drug Discovery Conference 19.03.15 San Diego, USA More science events from Research Highlights Top Cardiovascular disease: T cell activation in hypertension | Depression: Linking exercise and depression | Immunology: Myeloid cells mapped out | Cancer genomics: Mixed and matched tumors Review Top Ubiquitination in disease pathogenesis and treatment   pp1243 - 1253 Doris Popovic, Domagoj Vucic and Ivan Dikic doi:10.1038/nm.3739 Articles Top Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer's disease   pp1254 - 1262 Zhentao Zhang, Mingke Song, Xia Liu, Seong Su Kang, Il-Sun Kwon et al. doi:10.1038/nm.3700 Tau cleavage and aggregation, key processes in many neurodegenerative diseases, can be reduced by blocking the activity of a protease called asparagine endopeptidase. See also: News and Views by Rosenmann Niclosamide ethanolamine-induced mild mitochondrial uncoupling improves diabetic symptoms in mice   pp1263 - 1269 Hanlin Tao, Yong Zhang, Xiangang Zeng, Gerald I Shulman and Shengkan Jin doi:10.1038/nm.3699 By acting as a mild mitochondrial uncoupler, a derivative of the approved drug niclosamide may offer a new approach to treat diabetes. PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis   pp1270 - 1278 Hui Xie, Zhuang Cui, Long Wang, Zhuying Xia, Yin Hu et al. doi:10.1038/nm.3668 Preostoclasts secrete PDGF-BB to promote angiogenesis in the bone, promoting bone homeostasis and preventing bone loss in an osteoporosis model. Osteoblast-derived WNT16 represses osteoclastogenesis and prevents cortical bone fragility fractures   pp1279 - 1288 Sofia Moverare-Skrtic, Petra Henning, Xianwen Liu, Kenichi Nagano, Hiroaki Saito et al. doi:10.1038/nm.3654 A new study shows that Wnt16 inhibits osteoclast formation, suggesting it may be a possible therapeutic option for treating bone fractures in osteoporosis. See also: News and Views by Kusumbe & Adams Pro-proliferative and inflammatory signaling converge on FoxO1 transcription factor in pulmonary hypertension   pp1289 - 1300 Rajkumar Savai, Hamza M Al-Tamari, Daniel Sedding, Baktybek Kojonazarov, Christian Muecke et al. doi:10.1038/nm.3695 Activation of the transcription factor FoxO1 ameliorates vascular remodeling in pulmonary hypertension, pointing to a potential new therapeutic strategy for this disease. Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy   pp1301 - 1309 Antonella Sistigu, Takahiro Yamazaki, Erika Vacchelli, Kariman Chaba, David P Enot et al. doi:10.1038/nm.3708 Anthracyclines can induce a type 1 interferon response in tumor cells that may predict clinical response to these drugs. Letters Top An in vivo model of human small intestine using pluripotent stem cells   pp1310 - 1314 Carey L Watson, Maxime M Mahe, Jorge Munera, Jonathan C Howell, Nambirajan Sundaram et al. doi:10.1038/nm.3737 An in vivo model of the human small intestine is established in mice using human pluripotent stem cells. Megakaryocytes regulate hematopoietic stem cell quiescence through CXCL4 secretion   pp1315 - 1320 Ingmar Bruns, Daniel Lucas, Sandra Pinho, Jalal Ahmed, Michele P Lambert et al. doi:10.1038/nm.3707 Two papers in this issue, by Bruns et al. and Zhao et al., show that megakaryocytes constitute a niche for hematopoietic stem cells in the mouse bone marrow and produce factors that regulate hematopoietic stem cell quiescence and proliferation. See also: Article by Zhang et al. | News and Views by Day & Link Megakaryocytes maintain homeostatic quiescence and promote post-injury regeneration of hematopoietic stem cells   pp1321 - 1326 Meng Zhao, John M Perry, Heather Marshall, Aparna Venkatraman, Pengxu Qian et al. doi:10.1038/nm.3706 Two papers in this issue, by Bruns et al. and Zhao et al., show that megakaryocytes constitute a niche for hematopoietic stem cells in the mouse bone marrow and produce factors that regulate hematopoietic stem cell quiescence and proliferation. See also: News and Views by Day & Link | Letter by Bruns et al. De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells   pp1327 - 1333 Luciana Berod, Christin Friedrich, Amrita Nandan, Jenny Freitag, Stefanie Hagemann et al. doi:10.1038/nm.3704 TH17 and Treg cell development are reciprocally regulated by de novo fatty acid synthesis, and inhibition of acetyl-CoA carboxylase 1 (ACC1) attenuates TH17 cell-mediated autoimmune disease. See also: News and Views by O'Sullivan & Pearce Regulatory B cells are induced by gut microbiota-driven interleukin-1[beta] and interleukin-6 production   pp1334 - 1339 Elizabeth C Rosser, Kristine Oleinika, Silvia Tonon, Ronan Doyle, Anneleen Bosma et al. doi:10.1038/nm.3680 The gut microbiota promotes regulatory B cell development and function through interleukin-1[beta] and interleukin-6. Technical Reports Top A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer   pp1340 - 1347 Nina Schonhuber, Barbara Seidler, Kathleen Schuck, Christian Veltkamp, Christina Schachtler et al. doi:10.1038/nm.3646 The next generation of genetically engineered mouse models of pancreatic cancer involving a new inducible dual-recombinase system that combines Flp-FRT and Cre-loxP. Microscopic lymph node tumor burden quantified by macroscopic dual-tracer molecular imaging   pp1348 - 1353 Kenneth M Tichauer, Kimberley S Samkoe, Jason R Gunn, Stephen C Kanick, P Jack Hoopes et al. doi:10.1038/nm.3732 Tichauer et al. describe a dual-tracer approach to quantify cancer cell receptor concentrations, in this case epidermal growth factor receptor, in lymph nodes, that can also correct for nonspecific uptake. 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