Nature Medicine Contents: April 2015 Volume 21 Number 4 pp 295 - 414

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Advertisement Call for Applications: The 2016 Vilcek Prizes for Creative Promise in Biomedical Science $50,000 cash awards for young, foreign-born researchers Learn more about eligibility requirements and apply at Vilcek.org Deadline: June 15, 2015 TABLE OF CONTENTS April 2015 Volume 21, Issue 4 Editorial News News and Views Brief Communication Articles Letters Technical Report Corrigenda Errata Advertisement   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. Subscribe   Facebook   RSS   Recommend to library   Twitter   Podcast Advertisement Animation: Targeting cancer cell metabolism This animation, created by Nature Reviews Drug Discovery, with distribution supported by Forma Therapeutics, explores the key aspects of the altered metabolism in cancer cells and explains how these can be exploited for the development of new anticancer strategies.  Access the animation free online.   Produced with support from: Forma Therapeutics, Inc.    Editorial Top Germline editing: time for discussion   p295 doi:10.1038/nm.3845 News Top Reexamination casts doubt on brain tissue classified as healthy   pp296 - 297 Shraddha Chakradhar doi:10.1038/nm0415-296 After flu vaccine mismatch, calls for delayed selection intensify   pp297 - 298 Michele Cohen Marill doi:10.1038/nm0415-297 Warren joins lawmakers proposing new ideas for science funding   p299 Alan Dove doi:10.1038/nm0415-299 Questions raised about whether compulsory licenses get best prices   p300 Brian Owens doi:10.1038/nm0415-300 New model tackles sticky problem of getting drugs past mucus   p301 Juhie Bhatia doi:10.1038/nm0415-301 News in Brief Biomedical briefing   pp302 - 303 doi:10.1038/nm0415-302 News Feature Many returns: Call-ins and breakfasts hand back results to study volunteers   pp304 - 306 Shraddha Chakradhar doi:10.1038/nm0415-304 News and Views Top A mediator for malaria stickiness in A versus O blood   pp307 - 308 Liliana Mancio-Silva and Maria M Mota doi:10.1038/nm.3837 Malaria is thought to have shaped the worldwide distribution of human ABO blood but the underlying molecular details of this process have only recently started to be revealed. A new study provides insights on how malaria parasites interact with ABO blood group sugars, mediating rosetting events that cause severe disease. See also: Brief Communication by Goel et al. Harnessing gene repression to inhibit leukemia   pp308 - 310 Peter J Harte and Patricia Ernst doi:10.1038/nm.3834 Developing therapeutics for cancers targeting driver mutations in epigenetic regulators is a challenging frontier in cancer therapy. A new study identifies a pathway that, when activated, inhibits the actions of the histone methyltransferase DOT1L in MLL fusion leukemia. See also: Article by Chen et al. Beta cell glutamate receptor antagonists: novel oral antidiabetic drugs?   pp310 - 311 Claes B Wollheim and Pierre Maechler doi:10.1038/nm.3835 Type 2 diabetes occurs when the pancreatic beta cells fail to meet the increased insulin requirement in insulin-resistant individuals. A new therapeutic approach targeting glutamate receptors on beta cells improves insulin secretion and preserves beta cell mass. See also: Article by Marquard et al. Intracellular chloride accumulation: a possible mechanism for cognitive deficits in Down syndrome   pp312 - 313 Alberto C Costa doi:10.1038/nm.3836 A study involving a mouse model of Down syndrome and analysis of human postmortem brain samples indicates that hippocampal GABAA receptor signaling in Down syndrome may be excitatory. This advance promises new clinical applications in Down syndrome. See also: Article by Deidda et al. Nature Medicine JOBS of the week Research Associate Case Western Reserve University Postdoctoral research assistant Queen Mary University of London/Barts Cancer Institute Postdoctoral Scientist The Pirbright Institute Research Assistant University of Glasgow More Science jobs from Nature Medicine EVENT Obesity Summit 2016 12.04.16 London, UK More science events from Brief Communication Top RIFINs are adhesins implicated in severe Plasmodium falciparum malaria   pp314 - 317 Suchi Goel, Mia Palmkvist, Kirsten Moll, Nicolas Joannin, Patricia Lara et al. doi:10.1038/nm.3812 Goel et al. report that RIFINs mediate rosetting of Plasmodium falciparum infected erythrocytes in vitro, a phenotype that is associated with severe disease in humans See also: News and Views by Mancio-Silva & Mota Articles Top Reversing excitatory GABAAR signaling restores synaptic plasticity and memory in a mouse model of Down syndrome   pp318 - 326 Gabriele Deidda, Martina Parrini, Shovan Naskar, Ignacio F Bozarth, Andrea Contestabile et al. doi:10.1038/nm.3827 Both chronic and acute treatment of adult Ts65Dn mice with the FDA-approved NKCC1 inhibitor bumetanide suppressed aberrant excitatory GABAAR signaling and rescued synaptic plasticity deficits and cognitive disabilities in this mouse model of Down syndrome. See also: News and Views by Costa Prostaglandin E2 and programmed cell death 1 signaling coordinately impair CTL function and survival during chronic viral infection   pp327 - 334 Jonathan H Chen, Curtis J Perry, Yao-Chen Tsui, Matthew M Staron, Ian A Parish et al. doi:10.1038/nm.3831 Susan Kaech and colleagues report that in chronic viral infection, prostaglandin E2 and PD-1 signaling suppressed the function and survival of cytotoxic T cells. DOT1L inhibits SIRT1-mediated epigenetic silencing to maintain leukemic gene expression in MLL-rearranged leukemia   pp335 - 343 Chun-Wei Chen, Richard P Koche, Amit U Sinha, Aniruddha J Deshpande, Nan Zhu et al. doi:10.1038/nm.3832 The authors uncover the mechanism by which DOTL1 exerts its role as an epigenetic regulator required for leukemic progression by counteracting the effects of the chromatin regulators SIRT1 and SUV39H1. See also: News and Views by Harte & Ernst Targeting the MLL complex in castration-resistant prostate cancer   pp344 - 352 Rohit Malik, Amjad P Khan, Irfan A Asangani, Marcin Cieslik, John R Prensner et al. doi:10.1038/nm.3830 The MLL complex promotes androgen receptor signaling and drives growth of castration resistant prostate cancer Myocardial healing requires Reg3[beta]-dependent accumulation of macrophages in the ischemic heart   pp353 - 362 Holger Lorchner, Jochen Poling, Praveen Gajawada, Yunlong Hou, Viktoria Polyakova et al. doi:10.1038/nm.3816 After myocardial infarction, dedifferentiated cardiomyocytes secrete the protein Reg3[beta], thereby recruiting macrophages required for neutrophil clearance and myocardial healing. Characterization of pancreatic NMDA receptors as possible drug targets for diabetes treatment   pp363 - 372 Jan Marquard, Silke Otter, Alena Welters, Alin Stirban, Annelie Fischer et al. doi:10.1038/nm.3822 NMDA receptors in pancreatic beta cells inhibit glucose-stimulated insulin secretion, and inhibiting these receptors with an over-the-counter medication improves diabetes in mouse models See also: News and Views by Wollheim & Maechler Activation of AMPK[alpha]2 in adipocytes is essential for nicotine-induced insulin resistance in vivo    pp373 - 382 Yue Wu, Ping Song, Wencheng Zhang, Junhui Liu, Xiaoyan Dai et al. doi:10.1038/nm.3826 Nicotine acts on adipocytes to induce activation of AMPK, promoting excess lipolysis and weight loss but also the development of whole-body insulin resistance. Letters Top A high-throughput chemical screen reveals that harmine-mediated inhibition of DYRK1A increases human pancreatic beta cell replication   pp383 - 388 Peng Wang, Juan-Carlos Alvarez-Perez, Dan P Felsenfeld, Hongtao Liu, Sharmila Sivendran et al. doi:10.1038/nm.3820 A high-throughput chemical screen reveals that harmine and its analogs promote improved human pancreatic beta cell replication and function, thus identifying these molecules as a potential new class of antidiabetic agents. Genetic and functional characterization of clonally derived adult human brown adipocytes   pp389 - 394 Kosaku Shinoda, Ineke H N Luijten, Yutaka Hasegawa, Haemin Hong, Si B Sonne et al. doi:10.1038/nm.3819 Clonally-derived cell lines of human preadipocytes from BAT biopsies allows for the genetic and functional characterization of adipocytes from this tissue Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy   pp395 - 400 Jae Seok Lim, Woo-il Kim, Hoon-Chul Kang, Se Hoon Kim, Ah Hyung Park et al. doi:10.1038/nm.3824 Deep sequencing identifies somatic activating mutations of MTOR in affected brain regions of FCDII patients that are sufficient to cause neuronal migration defects and epileptic seizures in mice. A bacterial cyclic dinucleotide activates the cytosolic surveillance pathway and mediates innate resistance to tuberculosis   pp401 - 406 Bappaditya Dey, Ruchi Jain Dey, Laurene S Cheung, Supriya Pokkali, Haidan Guo et al. doi:10.1038/nm.3813 William Bishai and colleagues report that cyclic-di-adenosine monophosphate produced during infection with Mycobacterium tuberculosis induces IFN-[beta] and contributes to the innate sensing of tuberculosis. Technical Report Top Rapid mass spectrometric conversion of tissue biopsy samples into permanent quantitative digital proteome maps   pp407 - 413 Tiannan Guo, Petri Kouvonen, Ching Chiek Koh, Ludovic C Gillet, Witold E Wolski et al. doi:10.1038/nm.3807 A method for converting biopsy-size tissue samples into digital files containing the mass spectrometry-measurable proteome of the sample will allow analysis and re-analysis of limited tissue samples. Corrigenda Top Corrigendum: Inhibition of JAK-STAT signaling stimulates adult satellite cell function   p414 Feodor D Price, Julia von Maltzahn, C Florian Bentzinger, Nicolas A Dumont, Hang Yin et al. doi:10.1038/nm0415-414a Corrigendum: Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice   p414 Nicolas Wein, Adeline Vulin, Maria S Falzarano, Christina Al-Khalili Szigyarto, Baijayanta Maiti et al. doi:10.1038/nm0415-414b Corrigendum: Asfotase-[alpha] improves bone growth, mineralization and strength in mouse models of neurofibromatosis type-1   p414 Jean de la Croix Ndong, Alexander J Makowski, Sasidhar Uppuganti, Guillaume Vignaux, Koichiro Ono et al. doi:10.1038/nm0415-414c Errata Top Erratum: De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells   p414 Luciana Berod, Christin Friedrich, Amrita Nandan, Jenny Freitag, Stefanie Hagemann et al. doi:10.1038/nm0415-414d Erratum: A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer   p414 doi:10.1038/nm0415-414e Top Advertisement Nature Outlook Liver Cancer Liver cancer is one of the most lethal forms of the disease. 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