Nature Medicine Contents: February 2018 Volume 24 Number 2 pp 113-246

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Advertisement Do you have a career question?  The Naturejobs podcast features one-on-one Q&As, panel discussions and other exclusive content to help scientists with their careers. Hosted on the Naturejobs blog, the podcast is also available on iTunes and Soundcloud. Listen today! TABLE OF CONTENTS February 2018 Volume 24, Issue 2 Editorial News News and Views Articles Letters Advertisement Can you trust your Antibody? Implications for disease research. A recent publication in Scientific Reports rigorously tested nine commercially available antibodies for specificity and sensitivity and found that only one, from Cell Signaling Technology, met all validation criteria. Read this open-access article to explore the potentially serious implications of non-specific antibodies and disease research. Read more now. Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Outline: Fatty liver disease  The worldwide rise in obesity and diabetes has led to a spike in the incidence of non-alcoholic fatty liver disease, which often progresses to the more severe non-alcoholic steatohepatitis. This Outline discusses diagnostic techniques and therapies.  Access the Outline free online  Produced with support from: Gilead Sciences    Advertisement Spotlight on Kanagawa A smart place to work Lower house prices, proximity to Tokyo, and a burgeoning R&D ecosystem are thrusting Kanagawa into the modern world from its ancient history. Access Free Online   Editorial Top Taking personalized medicine to heart   p113 doi:10.1038/nm.4495 Tailoring treatment to the individual patient has revolutionized cancer therapy, but personalized medicine has yet to make much headway in the treatment of cardiovascular disease. With emerging insight into disease mechanisms and new treatment options, the time is now ripe for the cardiovascular field to adopt a more personalized approach to therapy. News Top News Feature Animals on the verge: What different species can teach us about human puberty   pp114 - 117 Shraddha Chakradhar doi:10.1038/nm0218-114 Correction   p117 doi:10.1038/nm0218-117 A shot at contraception: In India, a nonagenarian renews testing of a birth control vaccine   pp118 - 120 Killugudi Jayaraman doi:10.1038/nm0218-118 News and Views Top Gene therapies for hemophilia hit the mark in clinical trials   pp121 - 122 Adrian K Pickar and Charles A Gersbach doi:10.1038/nm.4492 Two recent studies describe clinical successes for single-dose gene therapy in trials for two forms of hemophilia. A potential biomarker for anti-PD-1 immunotherapy   pp123 - 124 Sangeeta Goswami, Sreyashi Basu and Padmanee Sharma doi:10.1038/nm.4489 A recent study identifies an immune cell type known as classical monocytes in the peripheral blood as a potential biomarker for response to anti-PD-1 immune checkpoint therapy in metastatic melanoma. See also: Article by Krieg et al. A new vaccine for tuberculosis in rhesus macaques   pp124 - 126 Stephen M Carpenter and Samuel M Behar doi:10.1038/nm.4488 In a recent study using cytomegalovirus (CMV)-vectored vaccines in rhesus macaques, prevention of tuberculosis in over 40% of vaccinated animals is shown and is attributed to reprogrammed innate immunity and CMV's maintenance of vaccine-elicited effector memory T cells. See also: Article by Hansen et al. Selective enhancer changes in osteosarcoma lung metastasis   pp126 - 127 Heinrich Kovar doi:10.1038/nm.4487 A recent study investigates the contribution of epigenomic plasticity to lung metastasis in osteosarcoma. Changes in the enhancer landscape were found to be nonrandom and driven by selective forces in the microenvironment. See also: Article by Morrow et al. Macrophages and platelets join forces to release kidney-damaging DNA traps   pp128 - 129 Dominik Hartl doi:10.1038/nm.4486 A recent study in mice dissects the mechanisms through which muscle damage leads to kidney dysfunction and identifies macrophage extracellular trap (MET) formation as a new pathogenic driver and potential therapeutic target. See also: Letter by Okubo et al. Nature Medicine JOBS of the week Postdoctoral Fellow University of Pennsylvania - Perelman School of Medicine Postdoctoral Research Training Fellowship City of Hope Postdoctoral Fellow University Health Network (Toronto) Postdoctoral Fellow University Health Network (Toronto) PhD Students and Postdoctoral Scientists University Medical Center Freiburg More Science jobs from Nature Medicine EVENT 2018 World Congress on Regional Anesthesia and Pain Medicine 18.04.18 New York, USA More science events from Advertisement Nature Outlook: Fatty liver disease The worldwide rise in obesity and diabetes has led to a spike in non-alcoholic fatty liver disease, which often progresses to the more severe non-alcoholic steatohepatitis. This Outlook discusses new diagnostic techniques and therapies.  Access the Outlook free online >> Produced with support from: Gilead Sciences    Articles Top Prevention of tuberculosis in rhesus macaques by a cytomegalovirus-based vaccine   pp130 - 143 Scott G Hansen, Daniel E Zak, Guangwu Xu, Julia C Ford, Emily E Marshall et al. doi:10.1038/nm.4473 Complete vaccine-mediated immune control of highly pathogenic Mycobacterium tuberculosis is possible if immune effector responses can intercept the infection at its earliest stages. See also: News and Views by Carpenter & Behar High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy   pp144 - 153 Carsten Krieg, Malgorzata Nowicka, Silvia Guglietta, Sabrina Schindler, Felix J Hartmann et al. doi:10.1038/nm.4466 Among many populations of blood cells, high dimensional analysis using mass cytometry reveals classical monocyte frequency as strong predictors of response to PD-1 blockade therapy of melanoma. See also: News and Views by Goswami et al. Recurrent ECSIT mutation encoding V140A triggers hyperinflammation and promotes hemophagocytic syndrome in extranodal NK/T cell lymphoma   pp154 - 164 Haijun Wen, Huajuan Ma, Qichun Cai, Suxia Lin, Xinxing Lei et al. doi:10.1038/nm.4456 A recurrent ECSIT mutation in individuals with extranodal natural killer/T cell lymphoma induces NFκB in cancer cells, leading to macrophage activation, and associates with progression to fatal hemophagocytic syndrome. NFκB-targeting therapy produced stable remission in two patients. Diverse genetic-driven immune landscapes dictate tumor progression through distinct mechanisms   pp165 - 175 Marco Bezzi, Nina Seitzer, Tomoki Ishikawa, Markus Reschke, Ming Chen et al. doi:10.1038/nm.4463 Pier Paolo Pandolfi and colleagues report that the genetic background of tumors in mice recruits specific immune-cell subsets, suggesting that precision medicine should account for both the tumor drivers and the distinct immune-cell microenvironments that they elicit. Positively selected enhancer elements endow osteosarcoma cells with metastatic competence   pp176 - 185 James J Morrow, Ian Bayles, Alister P W Funnell, Tyler E Miller, Alina Saiakhova et al. doi:10.1038/nm.4475 Peter Scacheri and colleagues report that the activity of enhancer elements in metastatic osteosarcoma is distinct from that in primary tumors and plays a functional role in metastatic progression of osteosarcoma. See also: News and Views by Kovar A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment   pp186 - 193 Marc L Hyer, Michael A Milhollen, Jeff Ciavarri, Paul Fleming, Tary Traore et al. doi:10.1038/nm.4474 Hyer et al. generate a potent and specific small-molecule inhibitor of the E1 ubiquitin-activating enzyme UBE1 that has antitumor activity in mice against a wide variety of tumor types. Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models   pp194 - 202 Michael L Schulte, Allie Fu, Ping Zhao, Jun Li, Ling Geng et al. doi:10.1038/nm.4464 A small molecule selectively targeting the cell-surface glutamine transporter ASCT2 disrupts glutamine signaling and metabolism. This compound displays low toxicity and strong antitumor activity in preclinical in vitro and in vivo models, thus holding promise as a treatment for glutamine-dependent tumors in a clinical setting. Cooperative targeting of melanoma heterogeneity with an AXL antibody-drug conjugate and BRAF/MEK inhibitors   pp203 - 212 Julia Boshuizen, Louise A Koopman, Oscar Krijgsman, Aida Shahrabi, Elke Gresnigt- van den Heuvel et al. doi:10.1038/nm.4472 Expression of AXL earmarks melanoma cells resistant to BRAF and MEK inhibitors that either pre-exist in treatment-naive tumors or emerge in response to therapy. The combination of an AXL-MMAE antibody-drug conjugate with BRAF and MEK inhibitors eliminates heterogeneous melanoma cell populations and prolongs survival in experimental in vivo models at tolerable toxicity. This approach is currently being tested in clinical trials and provides insights into the therapeutic targeting of intra-tumor heterogeneity. The deubiquitinating enzyme cylindromatosis mitigates nonalcoholic steatohepatitis   pp213 - 223 Yan-Xiao Ji, Zan Huang, Xia Yang, Xiaozhan Wang, Ling-Ping Zhao et al. doi:10.1038/nm.4461 The deubiquitinase CYLD regulates a TAK1-JNK pathway and can be targeted to ameliorate nonalcoholic steatohepatitis. Advertisement Nature Outline: Spinal-cord injury  There is currently no way to reverse damage to the spinal cord, nor restore the ability to move and feel that such an injury takes away. But regenerative therapies in early clinical testing are offering much-needed hope.  Access free online  Produced with support from  Translational Research Informatics Center (TRI) & Sapporo Medical University    Letters Top Transitory presence of myeloid-derived suppressor cells in neonates is critical for control of inflammation   pp224 - 231 Yu-Mei He, Xing Li, Michela Perego, Yulia Nefedova, Andrew V Kossenkov et al. doi:10.1038/nm.4467 Myeloid-derived suppressor cells are induced in newborn mice by breast-milk-derived lactoferrin and confer protection in a model of necrotizing enterocolitis. Their frequency and suppressive activity is decreased in very low-weight infants. Macrophage extracellular trap formation promoted by platelet activation is a key mediator of rhabdomyolysis-induced acute kidney injury   pp232 - 238 Koshu Okubo, Miho Kurosawa, Mako Kamiya, Yasuteru Urano, Akari Suzuki et al. doi:10.1038/nm.4462 Platelet activation after muscle trauma promotes extracellular trap release by macrophages and acute kidney injury. See also: News and Views by Hartl Suppression of luteinizing hormone enhances HSC recovery after hematopoietic injury   pp239 - 246 Enrico Velardi, Jennifer J Tsai, Stefan Radtke, Kirsten Cooper, Kimon V Argyropoulos et al. doi:10.1038/nm.4470 A luteinizing hormone-releasing hormone antagonist, used clinically for sex-steroid inhibition, promotes quiescence of hematopoietic stem cells and thereby promotes hematopoietic recovery and survival of lethally irradiated mice. 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