Nature Medicine Contents: March 2015 Volume 21 Number 3 pp 199-294

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Harrington Discovery Institute at University Hospitals in Cleveland, Ohio — part of The Harrington Project for Discovery & Development — announces the 2016 Harrington Scholar-Innovator Award, a search for physician-scientists seeking to advance promising discoveries into patient treatments. Letters of Intent accepted through May 1, 2015. Apply at HarringtonDiscovery.org.
TABLE OF CONTENTS
March 2015 Volume 21, Issue 3
	Editorial News Correspondence News and Views Between Bedside and Bench Review Articles Letters Technical Report
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The Biology of Regenerative Medicines (22-24 April 2015)Wellcome Trust Genome Campus, Hinxton, Cambridge, UK Join developmental-, regenerative- and stem cell biologists to discuss the biology of regeneration and how stem cells and the regenerative process can be exploited to treat disease. Abstract Deadline: 2 Mar. Registration Deadline: 20 Mar.
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Chronic Lymphocytic Leukemia: Recent advances in biology and therapy Access this new Collection from Leukemia available free online. Produced with support from: Janssen Pharmaceuticals Companies of Johnson & Johnson
EDITORIAL
A double-blind option for peer review   p199 doi:10.1038/nm.3817 Together with Nature and the other Nature-branded monthly journals, Nature Medicine is offering authors the option to remain anonymous during the peer-review process.
NEWS
Threat of interim data leaks prompts call for international rules   p200 Mollie Bloudoff-Indelicato doi:10.1038/nm0315-200
New technologies take root in the search for antibiotics from soil   p201 Jop de Vrieze doi:10.1038/nm0315-201
NEWS IN BRIEF
Biomedical briefing   pp202 - 203 doi:10.1038/nm0315-202
Insurance companies are slow to cover next-generation sequencing   pp204 - 205 Shraddha Chakradhar doi:10.1038/nm0315-204
Copy number variations' effect on drug response still overlooked   p206 Cassandra Willyard doi:10.1038/nm0315-206
Natural killers: Cataloging immune cells for immunotherapy   pp207 - 208 Amanda B. Keener doi:10.1038/nm0315-207
Training on trials: Patients taught the language of drug development   pp209 - 210 Shraddha Chakradhar doi:10.1038/nm0315-209
CORRESPONDENCE
Timing is everything for compassionate use of delamanid   p211 Clifton E Barry III doi:10.1038/nm.3823
NEWS AND VIEWS
Metabolic-epigenetic coupling in osteoclast differentiation   pp212 - 213 Lionel B Ivashkiv doi:10.1038/nm.3815 Osteoclasts are required for bone resorption. A new study in mice indicates that osteoclast differentiation is stabilized by DNA methylation at Irf8 (encoding interferon regulatory factor 8) mediated by DNA methyltransferase 3a (Dnmt3a), which suppresses Irf8 gene expression. The activity of Dnmt3 in osteoclasts requires elevated oxidative metabolism. See also: Letter by Nishikawa et al. Taming the inflammasome   pp213 - 215 Maayan Levy, Christoph A Thaiss and Eran Elinav doi:10.1038/nm.3808 The NLRP3 inflammasome is involved in the molecular etiology of multiple autoinflammatory diseases. Two studies identify inhibitors of NLRP3 activation and might pave the way for new treatment options for a variety of diseases. See also: Article by Coll et al. | Letter by Youmet al. Toward recreating colon cancer in human organoids   pp215 - 216 Ameen A Salahudeen and Calvin J Kuo doi:10.1038/nm.3818 Experimental modeling of cancer typically uses in vitro culture of transformed cell lines or in vivo animal models. A new study using CRISPR-Cas9 to engineer oncogenic mutations into three-dimensional human colon organoid cultures yields insights into colorectal cancer tumorigenesis. See also: Letter by Matano et al. Nature Medicine JOBS of the week Research Fellow University of Edinburgh Research Assistant University of Bristol Research Fellow TU Dresden, Dezernat 6, Sachgebiet Organisation Post doctoral scholar University of California - San Francisco More Science jobs from Nature Medicine EVENT BIO International Convention 2015  15.06.15 Philadelphia, USA More science events from
BETWEEN BEDSIDE AND BENCH
Understanding Biomarkers of Neurodegeneration: Ultrasensitive detection techniques pave the way for mechanistic understanding   pp217 - 219 Kaj Blennow and Henrik Zetterberg doi:10.1038/nm.3810 New methods for detecting indications of neurodegeneration are necessary to diagnose neurodegenerative diseases. In identifying suitable biomarkers that can be monitored by these techniques, the pathogenic mechanisms that lead to these diseases may also be elucidated.
Understanding Biomarkers of Neurodegeneration: Novel approaches to detecting tau pathology   pp219 - 220 Casey N Cook, Melissa E Murray and Leonard Petrucelli doi:10.1038/nm.3809 Tau pathology is commonly analyzed by positron emission tomography (PET) imaging. However, recently developed cell-based techniques for analyzing tau pathogenicity may also be used to measure an early biomarker in tauopathies.
REVIEW
Anemia: progress in molecular mechanisms and therapies   pp221 - 230 Vijay G Sankaran and Mitchell J Weiss doi:10.1038/nm.3814 The progress in understanding the mechanistic causes of anemias such as hemoglobinopathies and rare genetic disorders, as well as advances in therapies for anemias are reviewed.
ARTICLES
Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers   pp231 - 238 Benjamin G Bitler, Katherine M Aird, Azat Garipov, Hua Li, Michael Amatangelo et al. doi:10.1038/nm.3799 Ovarian tumors with common mutations in the epigenetic regulator ARID1A are shown to be sensitive to inhibition of EZH2, another epigenetic regulator, showing a synthetic lethality that could potentially be exploited therapeutically
LTB4 promotes insulin resistance in obese mice by acting on macrophages, hepatocytes and myocytes   pp239 - 247 Pingping Li, Da Young Oh, Gautam Bandyopadhyay, William S Lagakos, Saswata Talukdar et al. doi:10.1038/nm.3800 Genetic and pharmacological inhibition of the high-affinity LTB4 receptor promotes improved metabolism in obese mice.
A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases   pp248 - 255 Rebecca C Coll, Avril A B Robertson, Jae Jin Chae, Sarah C Higgins, Raul Munoz-Planillo et al. doi:10.1038/nm.3806 A selective, small-molecule inhibitor of NLRP3 suppresses activation of the inflammasome in vitro and in vivo and attenuates inflammatory disease. See also: News and Views by Levy et al. | Letter by Youm et al.
LETTERS
Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids   pp256 - 262 Mami Matano, Shoichi Date, Mariko Shimokawa, Ai Takano, Masayuki Fujii et al. doi:10.1038/nm.3802 Genome editing applied to human intestinal organoids enables the study of the functional effects of mutations recurrent in human tumors. See also: News and Views by Salahudeen & Kuo
The ketone metabolite [beta]-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease   pp263 - 269 Yun-Hee Youm, Kim Y Nguyen, Ryan W Grant, Emily L Goldberg, Monica Bodogai et al. doi:10.1038/nm.3804 Ketone bodies are elevated in response to fasting, a low-carbohydrate ketogenic diet or high-intensity exercise. Vishwa Deep Dixit and colleagues report that one metabolite, [beta]-hydroxybutyrate, inhibits the NLRP3 inflammasome. In vivo, [beta]-hydroxybutyrate is anti-inflammatory and suppresses NLRP3-mediated inflammatory disease. See also: News and Views by Levy et al. | Article by Coll et al.
Functional correction in mouse models of muscular dystrophy using exon-skipping tricyclo-DNA oligomers   pp270 - 275 Aurelie Goyenvalle, Graziella Griffith, Arran Babbs, Samir El Andaloussi, Kariem Ezzat et al. doi:10.1038/nm.3765 Use of a new generation anti-sense oligonucleotide to target exon skipping in multiple organ systems in two mouse models of muscular dystrophy
A C-terminal HSP90 inhibitor restores glucocorticoid sensitivity and relieves a mouse allograft model of Cushing disease   pp276 - 280 Mathias Riebold, Christian Kozany, Lee Freiburger, Michael Sattler, Michael Buchfelder et al. doi:10.1038/nm.3776 Inhibition of Hsp90 as its C-terminus allows for the mature folding of GR and its full activity, thus ameliorating Cushing symptoms in a mouse model.
DNA methyltransferase 3a regulates osteoclast differentiation by coupling to an S-adenosylmethionine-producing metabolic pathway   pp281 - 287 Keizo Nishikawa, Yoriko Iwamoto, Yasuhiro Kobayashi, Fumiki Katsuoka, Shin-ichi Kawaguchi et al. doi:10.1038/nm.3774 Proper bone structure is dependent on metabolism-mediated epigenetic regulation of osteoclast development. See also: News and Views by Ivashkiv
TECHNICAL REPORT
Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference-based bone anabolic strategy   pp288 - 294 Chao Liang, Baosheng Guo, Heng Wu, Ningsheng Shao, Defang Li et al. doi:10.1038/nm.3791
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