Nature Medicine Contents: June 2015 Volume 21 Number 6 pp 539 - 653

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Advertisement The Harrington Prize for Innovation in Medicine - Nominations due August 28, 2015. The Harrington Prize for Innovation in Medicine, presented by the American Society for Clinical Investigation and the Harrington Discovery Institute, honors the physician-scientist who has moved science forward with notable achievements in innovation, creativity and potential for clinical application. The Harrington Prize includes an unrestricted $20,000 honorarium. Submit a nomination at http://www.HarringtonDiscovery.org. TABLE OF CONTENTS June 2015 Volume 21, Issue 6 Editorial News News and Views Brief Communications Articles Letter Subscribe   Facebook   RSS   Recommend to library   Twitter   Podcast Advertisement Nephrology in the developing world This special issue of Nature Reviews Nephrology has been commissioned to shed light on a range of issues facing the renal health of the developing world, from infectious agents that manifest in the kidneys to setting up treatment facilities in challenging circumstances. Access the focus issue online   Editorial Top Let research bloom   p539 doi:10.1038/nm.3879 Recent news of raids on research budgets illustrates how precarious government funding of scientific research has become. In an era of unprecedented momentum in the development of technologies and therapies for studying and treating disease, opportunities for new discoveries must not be lost due to shortsighted budgetary concerns. News Top Updated, augmented vaccines compete with original antigenic sin   pp540 - 541 Shraddha Chakradhar doi:10.1038/nm0615-540 New consent requirements for newborn screening raise concerns   pp542 - 543 Wudan Yan doi:10.1038/nm0615-542 Microbiome models, on computers and in lab dishes, see progress   pp543 - 544 Jop de Vrieze doi:10.1038/nm0615-543 Binding time[mdash]not just affinity[mdash]gains stature in drug design   p545 Wudan Yan doi:10.1038/nm0615-545 News in Brief Biomedical briefing   pp546 - 547 doi:10.1038/nm0615-546 News and Views Top Regulation of immunopathology in hepatitis B virus infection   pp548 - 549 Silvia Piconese and Vincenzo Barnaba doi:10.1038/nm.3873 In the liver there is a fine balance between immune surveillance of blood-borne infections and regulation of immunopathology. A new study identifies a role for granulocytic myeloid-derived suppressor cells in limiting T cell-mediated immunopathology in hepatitis B virus infection. See also: Article by Pallett et al. Converting smooth muscle cells to macrophage-like cells with KLF4 in atherosclerotic plaques   pp549 - 551 Michael E Rosenfeld doi:10.1038/nm.3875 Atherosclerosis is the primary cause of heart attacks and strokes and is caused by a chronic inflammatory response in the coronary and carotid arteries. A new study shows that smooth muscle cells within atherosclerotic plaques can change phenotypes to become macrophage-like cells, thereby revealing the remarkable plasticity of these cells. See also: Article by Shankman et al. Unpleasant memories: tissue-embedded T cell memory drives skin hypersensitivity   pp551 - 552 Thomas Gebhardt and Francis R Carbone doi:10.1038/nm.3874 Tissue-resident memory T cells (TRM cells) protect against recurrent or renewed infection in barrier tissues such as skin and mucosa. A new study sheds light on the clonal origin of TRM cells and demonstrates a crucial role for tissue-embedded T cell memory in contact hypersensitivity in skin. See also: Letter by Gaide et al. Mutant PRPS1: a new therapeutic target in relapsed acute lymphoblastic leukemia   pp553 - 554 Charles G Mullighan doi:10.1038/nm.3876 A new study identifies recurrent mutations in the purine biosynthesis gene phosphoribosyl pyrophosphate synthetase 1 (PRPS1) in relapsed acute lymphoblastic leukemia (ALL). This work highlights the importance of this pathway in the pathogenesis of relapse and suggests an approach to predicting and circumventing resistance in ALL. See also: Article by Li et al. Nature Medicine JOBS of the week PhD position University of Fribourg Junior Group Leader CNRS & University of Toulouse Post Doctoral Fellow / Research Associate Emory University Postdoctoral Fellow The BloodCenter of Wisconsin More Science jobs from Nature Medicine EVENT SMODIA "Statistical Methods for Omics Data Integration and Analysis 2015" 14.09.15 Valencia, Spain More science events from Brief Communications Top Functionally defined therapeutic targets in diffuse intrinsic pontine glioma   pp555 - 559 Catherine S Grasso, Yujie Tang, Nathalene Truffaux, Noah E Berlow, Lining Liu et al. doi:10.1038/nm.3855 The study describes the use of integrative approaches to search for candidate therapeutic targets for DIPG, and the identification of an HDAC inhibitor as a potential treatment strategy Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M   pp560 - 562 Kenneth S Thress, Cloud P Paweletz, Enriqueta Felip, Byoung Chul Cho, Daniel Stetson et al. doi:10.1038/nm.3854 A mutation conferring resistance to novel irreversible EGFR inhibitors is identified in cell-free plasma DNA from lung cancer patients. Articles Top Negative feedback-defective PRPS1 mutants drive thiopurine resistance in relapsed childhood ALL   pp563 - 571 Benshang Li, Hui Li, Yun Bai, Renate Kirschner-Schwabe, Jun J Yang et al. doi:10.1038/nm.3840 The authors uncover new mutations in an enzyme from the purine synthesis pathway that cause resistance to leukemia therapy, and reveal a new mechanism by which they affect drug metabolism. See also: News and Views by Mullighan The Cyclophilin A-CD147 complex promotes the proliferation and homing of multiple myeloma cells   pp572 - 580 Di Zhu, Zhongqiu Wang, Jian-Jun Zhao, Teresa Calimeri, Jiang Meng et al. doi:10.1038/nm.3867 Cyclophilin A, secreted by bone marrow endothelial cells, acts as a chemotactic factor for myeloma cells, which helps explain their homing to the bone marrow and suggests a potential new therapeutic strategy. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors   pp581 - 590 Adrienne H Long, Waleed M Haso, Jack F Shern, Kelsey M Wanhainen, Meera Murgai et al. doi:10.1038/nm.3838 Crystal Mackall and colleagues report that antigen-independent signaling of chimeric antigen receptors (CARs) causes T cell exhaustion and reduced therapeutic efficacy of CAR T cells that can be overcome by incorporating the 4-1BB costimulatory domain into the CAR. Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells   pp591 - 600 Laura J Pallett, Upkar S Gill, Alberto Quaglia, Linda V Sinclair, Maria Jover-Cobos et al. doi:10.1038/nm.3856 Pallett et al. report that myeloid derived suppressor cells expand, home to the liver, and inhibit T cell-mediated liver damage in chronic hepatitis B virus infection. See also: News and Views by Piconese & Barnaba Pharmacological targeting of actin-dependent dynamin oligomerization ameliorates chronic kidney disease in diverse animal models   pp601 - 609 Mario Schiffer, Beina Teng, Changkyu Gu, Valentina A Shchedrina, Marina Kasaikina et al. doi:10.1038/nm.3843 The small molecule Bis-T-23 targets actin polymerization to improve renal morphology and function in several mouse models of kidney injury and disease. Irf5 deficiency in macrophages promotes beneficial adipose tissue expansion and insulin sensitivity during obesity   pp610 - 618 Elise Dalmas, Amine Toubal, Fawaz Alzaid, Katrina Blazek, Hayley L Eames et al. doi:10.1038/nm.3829 Deletion of the transcription factor Irf5 in macrophages leads to expansion of the subcutaneous fat depot but restriction of the visceral fat during obesity, resulting in improved insulin sensitivity The microRNA-200 family regulates pancreatic beta cell survival in type 2 diabetes   pp619 - 627 Bengt-Frederik Belgardt, Kashan Ahmed, Martina Spranger, Mathieu Latreille, Remy Denzler et al. doi:10.1038/nm.3862 The miR-200 family of miRNAs is upregulated in diabetes and leads to the apoptosis of pancreatic beta cells, while its knockout prevents this pathology KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis   pp628 - 637 Laura S Shankman, Delphine Gomez, Olga A Cherepanova, Morgan Salmon, Gabriel F Alencar et al. doi:10.1038/nm.3866 A high percentage of smooth muscle cells in atherosclerotic lesions lose expression of smooth muscle marker proteins and acquire the phenotype of other cell types, a process of functional importance in lesion pathogenesis that is controlled by the transcription factor KLF4. See also: News and Views by Rosenfeld Metabolic control of type 1 regulatory T cell differentiation by AHR and HIF1-[alpha]   pp638 - 646 Ivan D Mascanfroni, Maisa C Takenaka, Ada Yeste, Bonny Patel, Yan Wu et al. doi:10.1038/nm.3868 Metabolic changes induced by hypoxia and extracellular ATP, acting through the transcription factors HIF1-[alpha] and AHR, regulate the differentiation of type 1 regulatory (Treg1) cells. Letter Top Common clonal origin of central and resident memory T cells following skin immunization   pp647 - 653 Olivier Gaide, Ryan O Emerson, Xiaodong Jiang, Nicholas Gulati, Suzanne Nizza et al. doi:10.1038/nm.3860 Following skin immunization a common naive T cell precursor gives rise to resident and central memory T cells, which mediate rapid and delayed skin immune responses, respectively. See also: News and Views by Gebhardt & Carbone Top Advertisement Celebrating the 25th Anniversary of SELEX: An Aptamer Symposium Supported by the American Society of Gene & Cell Therapy, the Aptamers Workshop will provide a unique opportunity to celebrate the 25th anniversary of aptamers and to meet researchers around the world developing nucleic acid aptamers as high affinity targeting reagents for both diagnosis and therapy. Find out more: www.asgct.org/am15/   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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