Nature Medicine Contents: July 2017 Volume 23 Number 7 pp 789-898

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Advertisement From Bench to Bedside and Back Again Charles River has proudly partnered with the EBD Group to provide the scientific program for this year's BioPharm America™ Conference. Be a part of this two-day conference that aims to bridge the gap between drug discovery and clinical application. Register now>> TABLE OF CONTENTS July 2017 Volume 23, Issue 7 Editorials News Correction News and Views Perspective Brief Communication Articles Letter Technical Reports Advertisement   Nature Index China 2017 China continues to increase its global share of research papers, but publication numbers are just one indicator that a country's science is thriving. Read the full supplement free for six months Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Index Japan 2017  Japan's status as a science superstar is vulnerable. Nature Index 2017 Japan reveals that although the country is still among the upper echelons of global research, its output has continued to slide. Read the full supplement free for six months     Advertisement Focus on Disease models: reproducibility and translation  Lab Animal, a Nature Research journal focusing on in vivo methods, research and technology with model organisms of human health & disease, presents a special Focus on reproducibility and translation of in vivo research with disease models.  Access this Focus > Produced with support from:  Taconic Biosciences, Inc.  Charles River   Advertisement NATURE CONFERENCE ON INFLAMMATORY DISEASES Presented by: Chinese Academy of Medical Sciences & Peking Union Medical College | Chinese Society for Immunology (CSI) | Nature Reviews Immunology | Nature Immunology | Nature | Nature Communications This conference will feature sessions on microbiota, cell death, metabolism, technologies, and innate sensing and signaling as they relate to inflammatory diseases and cancer. September 17-20, 2017 | Beijing, China REGISTER NOW!   Editorials Top A prescription for cancer diagnostics   p789 doi:10.1038/nm.4371 Cancer research has made great strides in identifying effective therapies for treating advanced-stage tumors. The next challenge is moving the battle to earlier stages of disease. Battling the biology of opioid addiction   p790 doi:10.1038/nm.4374 Deaths from drug overdose are rising worldwide, in part owing to the growing epidemic of opioid addiction. Efforts to combat opioid addiction will benefit from stronger collaboration between preclinical researchers who are studying addiction and those studying chronic pain. News Top Medicine's movable feast: What jumping genes can teach us about treating disease   pp791 - 795 Roxanne Khamsi doi:10.1038/nm0717-791 Put to the test: Organoid-based testing becomes a clinical tool   pp796 - 799 Shraddha Chakradhar doi:10.1038/nm0717-796 Correction Top Correction   p799 doi:10.1038/nm0717-799 News and Views Top An unexpected role for bile acid synthesis in adaptation to low temperature   pp800 - 802 Folkert Kuipers and Albert K Groen doi:10.1038/nm.4365 Enhanced conversion of dietary cholesterol to bile acids through the alternative pathway leads to cold-associated, metabolically beneficial changes in the intestinal microbiome and to elevated bile acid levels that contribute to adaptive thermogenesis. See also: Article by Worthmann et al. A mouse model of renal cell carcinoma   pp802 - 803 Laura S Schmidt and W Marston Linehan doi:10.1038/nm.4366 A mouse model with combined renal epithelium-specific deletion of Vhl, Trp53 and Rb1 that develops clear-cell renal cell carcinoma provides a research tool for investigating the mechanisms that drive this cancer, and for evaluating the efficacy of novel therapeutic agents. See also: Article by Harlander et al. Nature Medicine JOBS of the week Post-doctoral Position in Cancer Genomics and Precision Medicine Candiolo Cancer Institute-FPO, IRCCS Associate Editor, Science Translational Medicine American Association for the Advancement of Science Multiple Opportunities in Molecular Neuroscience Loyola University Chicago - Stritch School of Medicine Postdoctoral Fellow Case Western Reserve University, School of Medicine Chair, Department of Microbiology and Immunology Rosalind Franklin University of Medicine and Science More Science jobs from Nature Medicine EVENT MICCAI Computational Biomechanics for Medicine Workshop 14.09.17 Québec City, Canada More science events from Perspective Top Insulin action and resistance in obesity and type 2 diabetes   pp804 - 814 Michael P Czech doi:10.1038/nm.4350 In this Perspective, Michael Czech presents evidence for whether hyperinsulinemia occurs before insulin resistance upon overfeeding or high-fat diet feeding, or whether insulin resistance causes hyperinsulinemia, thus attempting to delineate the relationship between hyperinsulinemia, obesity and insulin resistance. Brief Communication Top Elimination of large tumors in mice by mRNA-encoded bispecific antibodies   pp815 - 817 Christiane R Stadler, Hayat Bahr-Mahmud, Leyla Celik, Bernhard Hebich, Alexandra S Roth et al. doi:10.1038/nm.4356 Bispecific antibodies that connect T cells with tumor cells can be delivered in the form of in vitro-transcribed pharmacologically optimized mRNA; when injected into mice, these mRNA-encoded antibodies reject large established tumors as efficiently as the corresponding recombinant antibody protein. Advertisement Nature Outlook: Animal Health Animal and human health are closely linked. This Outlook examines how climate change is pushing diseases into formerly 'safe' regions of the world, the challenges in treating parasites, the efforts to vaccinate gorillas against Ebola and how a holistic approach to disease could further the well-being of animals.  Access the Outlook free online   Produced with support from  Bayer Animal Health GmbH    Articles Top Interaction of reactive astrocytes with type I collagen induces astrocytic scar formation through the integrin-N-cadherin pathway after spinal cord injury   pp818 - 828 Masamitsu Hara, Kazu Kobayakawa, Yasuyuki Ohkawa, Hiromi Kumamaru, Kazuya Yokota et al. doi:10.1038/nm.4354 In a mouse model of spinal cord injury, reactive astrogliosis is found to be context dependent and reversible. Blockade of type I collagen-reactive astrocyte interactions prevents astrocyte scar formation and facilitates functional recovery after injury. Thermoneutral housing exacerbates nonalcoholic fatty liver disease in mice and allows for sex-independent disease modeling   pp829 - 838 Daniel A Giles, Maria E Moreno-Fernandez, Traci E Stankiewicz, Simon Graspeuntner, Monica Cappelletti et al. doi:10.1038/nm.4346 Current mouse models of nonalcoholic steatohepatitis are limited, making identification and preclinical testing of new treatments challenging. Housing mice at thermoneutrality leads to less stress, a stronger immune response and better modeling of this condition. Cold-induced conversion of cholesterol to bile acids in mice shapes the gut microbiome and promotes adaptive thermogenesis   pp839 - 849 Anna Worthmann, Clara John, Malte C Ruhlemann, Miriam Baguhl, Femke-Anouska Heinsen et al. doi:10.1038/nm.4357 During cold stimulation, cholesterol is converted to bile acids in an alternative pathway. The bile acids then alter the microbiota, which in turn promotes more heat generation. See also: News and Views by Kuipers & Groen Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug   pp850 - 858 Hao Wu, Eduardo Esteve, Valentina Tremaroli, Muhammad Tanweer Khan, Robert Caesar et al. doi:10.1038/nm.4345 A randomized clinical trial reveals that the antidiabetic effects of metformin are at least partially due to beneficial changes in the microbiota. Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention   pp859 - 868 Ruixin Liu, Jie Hong, Xiaoqiang Xu, Qiang Feng, Dongya Zhang et al. doi:10.1038/nm.4358 Composition of gut bacteria and serum metabolites in young, obese individuals is partially restored following weight loss surgery, including Bacteroides thetaiotaomicron, which decreases serum glutamate levels and fat mass gain in mice. Combined mutation in Vhl, Trp53 and Rb1 causes clear cell renal cell carcinoma in mice   pp869 - 877 Sabine Harlander, Desiree Schonenberger, Nora C Toussaint, Michael Prummer, Antonella Catalano et al. doi:10.1038/nm.4343 Through combined deletion of Vhl, Trp53 and Rb1 in renal epithelial cells, the authors develop a new mouse model of renal cell carcinoma that recapitulates the cellular and molecular features of a large proportion of human tumors. This model uncovers a role for primary-cilium-related genes in the development of the disease and provides a reliable platform for preclinical therapeutic studies. See also: News and Views by Schmidt & Linehan Advertisement Scientific rigour and reproducibility  Science progresses by standing on the shoulders of giants, to paraphrase Newton. But what if those shoulders aren't steady? Read about how to assess and improve the reliability of biomedical research.  Access this Collection of articles free online Produced with support from:  Gilson & sciNote   Letter Top Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing   pp878 - 884 Miguel Crespo, Eduardo Vilar, Su-Yi Tsai, Kyle Chang, Sadaf Amin et al. doi:10.1038/nm.4355 A protocol based on chemical modulation of WNT activity is used to efficiently generate colonic organoids that recapitulate the molecular features of human colon tissue. Colonic organoids generated from induced pluripotent stem cells from patients with familial adenomatous polyposis provide an in vitro platform for disease modeling and preclinical drug testing. Technical Reports Top Novel assay reveals a large, inducible, replication-competent HIV-1 reservoir in resting CD4+ T cells   pp885 - 889 Anwesha Sanyal, Robbie B Mailliard, Charles R Rinaldo, Deena Ratner, Ming Ding et al. doi:10.1038/nm.4347 Sanyal et al. report a new and rapid assay for measuring replication-competent HIV-1 in CD4+ T cells. ISDoT: in situ decellularization of tissues for high-resolution imaging and proteomic analysis of native extracellular matrix   pp890 - 898 Alejandro E Mayorca-Guiliani, Chris D Madsen, Thomas R Cox, Edward R Horton, Freja A Venning et al. doi:10.1038/nm.4352 By surgically directing the vascular delivery of decellularization reagents, the in situ decellularization of desired organs or tissues in mice can be achieved, enabling detailed imaging and characterization of the intact extracellular matrix, including in the cancer metastatic niche. Top Advertisement Call for nominations: 2017 John Maddox Prize for Standing up for Science. Recognising the work of individuals who promote science in the face of hostility. Winners will be announced at a reception in London, as well as in Nature, and will receive £2,000. Closing date for nominations is 31st July 2017. Click to learn more   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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