Nature Medicine Contents: January 2013 Volume 20 Number 1 pp 1-103

If you are unable to see the message below, click here to view.

TABLE OF CONTENTS January 2014 Volume 20, Issue 1 Podcast Editorial News Correction Book Review News and Views Community Corner Between Bedside and Bench Research Highlights Articles Letters Technical Reports Corrigendum Subscribe   Facebook   RSS   Recommend to library   Twitter   Podcast Advertisement Web Collection on Hepatocellular carcinoma from Nature Reviews Clinical Oncology and Nature Reviews Gastroenterology & Hepatology This web collection includes a selection of articles covering key aspects of the pathogenesis and treatment of HCC, including insights into disease pathways and possible future therapeutic targets.  FREE for a limited time!  This Collection is produced with educational support from Onyx Pharmaceuticals, Inc. and Bayer Healthcare LLC     Nature Medicine Podcast  Top Alcohol content We speak with the incoming chief of the NIH alcohol institute and examine how to target self-renewal in cancer stem cells. Listen Now Editorial Top Finding common ground in cancer research   p1 doi:10.1038/nm.3456 Reproducibility in science is a prominent topic in both lay and scientific press. But a new facet of this discussion has arisen in a recent comparison of two pharmacogenomic studies, and it calls for an evaluation of how we interpret science in the face of discrepant results. News Top Revved-up epigenetic sequencing may foster new diagnostics   p2 Arielle Duhaime-Ross doi:10.1038/nm0114-2 Multicompany trials adapt to disciplines beyond cancer   p3 Asher Mullard doi:10.1038/nm0114-3 Juno's whopping [dollar]120 million success signals new investing style   pp4 - 5 Cassandra Willyard doi:10.1038/nm0114-4 Infectious disease leads in first phase of Europe's IMI effort   p5 doi:10.1038/nm0114-5 News in Brief Biomedical briefing   pp6 - 7 doi:10.1038/nm0114-6 Correction Top Correction   p7 doi:10.1038/nm0114-7 News Top Q&A Straight talk with...George Koob   p8 doi:10.1038/nm0114-8 On 27 January, the US National Institute on Alcohol Abuse and Alcoholism (NIAAA) will welcome George Koob as its new permanent head. A neurobiologist at the Scripps Research Institute in La Jolla, California, for the past 30 years, Koob, 66, made his name both in the study of alcoholism and in addiction to other substances. His work has long been funded by both NIAAA and NIDA. Elie Dolgin spoke with Koob about what he thinks sets alcohol research apart. News Feature Encapsulate this   pp9 - 11 Elie Dolgin doi:10.1038/nm0114-9 Insulin-producing islet cells could hold the secret to curing type 1 diabetes[mdash]if only scientists could figure out a way to encapsulate and transplant them into the body. But first, the right biocompatible material must be found to hold these precious cells. A team of bioengineers thinks it has discovered one. Elie Dolgin reports. Opinion Partnering with local scientists should be mandatory   p12 Miriam Shuchman, Dawit Wondimagegn, Clare Pain and Atalay Alem doi:10.1038/nm0114-12 The problem of inequity in international research is perpetuated by policies that enable scientists to conduct research in lower-resourced areas of the world without partnering with local researchers. The World Health Organization (WHO) needs to lead in solving this problem by working with research institutions, journal editors and funding agencies to document the degree of inequity and to impose penalties for failures to collaborate. Book Review Top TB's terrible toll   p13 Ian Orme reviews Spitting Blood: The History of Tuberculosis by Helen Bynum doi:10.1038/nm.3366 News and Views Top Targeting self-renewal, an Achilles' heel of cancer stem cells   pp14 - 15 Max S Wicha doi:10.1038/nm.3434 Many tumors display a hierarchical organization that is maintained by a self-renewing 'cancer stem cell' population. A new study in mice shows that targeting the self-renewal regulator BMI-1 abrogates the tumorigenic capacity of colon cancer stem cells, providing a new therapeutic strategy (pages 29-36). See also: Article by Kreso et al. Good guys gone bad: exTreg cells promote autoimmune arthritis   pp15 - 17 Nicole Joller and Vijay K Kuchroo doi:10.1038/nm.3439 Under most circumstances, Foxp3+ regulatory T (Treg) cells are a stable T cell population essential for maintaining self-tolerance. A study now shows that the inflammatory environment in autoimmune arthritis induces conversion of a subset of Foxp3+ T cells into interleukin-17-producing cells that contribute to disease pathogenesis (pages 62-68). See also: Article by Komatsu et al. Hepatocytes break the silence during liver-stage malaria   pp17 - 19 Ashraful Haque and Christian Engwerda doi:10.1038/nm.3446 Liver-stage Plasmodium infection triggers a type I interferon transcriptional program in hepatocytes that amplifies an innate immune response within hepatic myeloid cells. This minimizes liver parasite load and delays the release of disease-causing parasites into the bloodstream (pages 47-53). See also: Article by Liehl et al. An innate link between obesity and asthma   pp19 - 20 Juan C Celedon and Jay K Kolls doi:10.1038/nm.3433 The concordant epidemics of asthma and obesity are both associated with inflammation, and obesity has been shown to be an independent risk factor for asthma. A new study in mice indicates that part of the immunological connection between obesity and asthma involves inflammasome activation and production of the cytokine interleukin-17 by innate lymphoid cells in the lung (pages 54-61). See also: Article by Kim et al. Nature Medicine JOBS of the week Post Doctoral Fellow The Wistar Institute Post-doctoral researcher University of Patras PhD posititon - Immunology University Hospital Erlangen Postdoctoral Scientist University of Oxford More Science jobs from Nature Medicine EVENT Next Generation Sequencing 13.04.14 Cambridge, UK More science events from Community Corner Top A new unexpected twist in newborn immunity   pp22 - 23 doi:10.1038/nm.3448 Between Bedside and Bench Top The Many Faces of Sirtuins: Sirtuins and the Warburg effect   pp24 - 25 Leonard Guarente doi:10.1038/nm.3438 Metabolic regulators that permit adaptation to changes in caloric intake have been shown to be needed to protect from age-related disorders. Sirtuins play a crucial part in this program, impinging on not only aging but also other diseases. New findings are uncovering the multifaceted activity of sirtuins in living organisms and their effects on healthspan. In 'Bedside to Bench', Leonard Guarente discusses how different sirtuins are hindering cancer metabolism through suppression of the Warburg effect. The apparent antitumor effects of several sirtuins through their regulation of different metabolic pathways suggest therapeutic approaches to induce sirtuin function or that of downstream targets may block cancer growth. In 'Bench to Bedside', Eric Verdin peruses a few studies in different animal models showing that increased amounts of nicotinamide adenine dinucleotide (NAD), a cofactor of sirtuins, may have a positive effect in longevity and span of healthy life, or healthspan, by increasing sirtuin enzymatic activity. Whether harnessing NAD therapeutically is a potential way to extend lifespan and ameliorate diseases is still open to debate. The Many Faces of Sirtuins: Coupling of NAD metabolism, sirtuins and lifespan   pp25 - 27 Eric Verdin doi:10.1038/nm.3447 Research Highlights Top Cancer: Extrachromosomal resistance | Autism: Bacterial link to autistic behaviors | Skeletal muscle: Muscular Treg cells | Vaccines: Vaccine stresses out DCs Advertisement "Frontiers has taken open access a step further" Andy Bhattacharjee In this video, Andy Bhattacharjee tells us what he likes about publishing at Frontiers - open access and interactive peer review. Find Andy on the Frontiers Research Network   Articles Top Self-renewal as a therapeutic target in human colorectal cancer   pp29 - 36 Antonija Kreso, Peter van Galen, Nicholas M Pedley, Evelyne Lima-Fernandes, Catherine Frelin et al. doi:10.1038/nm.3418 Cancer stem cells are thought to be resistant to anticancer therapies and are able to repopulate tumors and sustain tumor growth. The authors establish BMI-1 as a crucial regulator of cancer cell stemness in colorectal tumors and develop a chemical inhibitor that targets cancer stem cell renewal by reducing the levels of BMI-1. This strategy affords antitumor effects in vitro and in vivo and may pave the way for the precise targeting of elusive cancer stem cells. See also: News and Views by Wicha Circulating angiopoietin-like 4 links proteinuria with hypertriglyceridemia in nephrotic syndrome   pp37 - 46 Lionel C Clement, Camille Mace, Carmen Avila-Casado, Jaap A Joles, Sander Kersten et al. doi:10.1038/nm.3396 Nephrotic syndrome is marked by excess of both protein in the urine (proteinuria) and triglycerides in the blood (hypertriglyceridemia). Sumant Chugh and his colleagues now explain these linked pathologies while also suggesting a possible new therapy to treat the proteinuria without aggravating the hypertriglyceridemia. Host-cell sensors for Plasmodium activate innate immunity against liver-stage infection   pp47 - 53 Peter Liehl, Vanessa Zuzarte-Luis, Jennie Chan, Thomas Zillinger, Fernanda Baptista et al. doi:10.1038/nm.3424 After mosquito bite, the malaria parasite first infects the liver, where it is thought to be undetected by the host immune system as it develops into the blood-stage pathogen. Maria Mota and her colleagues now report that Plasmodium RNA is detected by hepatocytes, triggering an interferon response that controls the parasite burden in the liver and blood of infected mice. See also: News and Views by Haque & Engwerda Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity   pp54 - 61 Hye Young Kim, Hyun Jun Lee, Ya-Jen Chang, Muriel Pichavant, Stephanie A Shore et al. doi:10.1038/nm.3423 The mechanisms underlying the association between obesity and the development of asthma remain incompletely understood. Dale T. Umetsu and his colleagues report that the number of IL-17A+ type 3 innate lymphoid cells (ILCs) is increased in the lungs of mice fed a high-fat diet. Activation of the NLRP3 inflammasome in lung macrophages promotes IL-1[beta] production and ILC development, and blockade of IL-1 signaling inhibits airway hyperreactivity in obese mice. As these ILCs are also found in the lungs of individuals with asthma, these results suggest that this pathway may be targeted in asthma. See also: News and Views by Celedon & Kolls Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis   pp62 - 68 Noriko Komatsu, Kazuo Okamoto, Shinichiro Sawa, Tomoki Nakashima, Masatsugu Oh-hora et al. doi:10.1038/nm.3432 Regulatory T (Treg) cells exhibit substantial phenotypic and functional plasticity. Hiroshi Takayanagi and his colleagues report that in autoimmune arthritis, a subset of Treg cells can lose Foxp3 expression and convert into TH17 cells. This conversion is mediated by synovial fibroblast-derived IL-6, and in vivo, these cells are osteoclastogenic and exacerbate arthritis. These findings suggest that a proportion of pathogenic TH17 cells in autoimmune disease may be derived from Treg cells. See also: News and Views by Joller & Kuchroo Letters Top Regulatory T cell proliferative potential is impaired in human autoimmune disease   pp69 - 74 Fortunata Carbone, Veronica De Rosa, Pietro B Carrieri, Silvana Montella, Dario Bruzzese et al. doi:10.1038/nm.3411 The suppressive function and number of regulatory T cells (Treg cells) is reduced in autoimmune disease. Here, Giuseppe Matarese and colleagues report that Treg cell proliferation is reduced in subjects with relapsing-remitting multiple sclerosis. As disease severity increases, Treg cell proliferation progressively decreases and is associated with impaired IL-2 release and IL-2 receptor and mTOR signaling. Sterilization of granulomas is common in active and latent tuberculosis despite within-host variability in bacterial killing   pp75 - 79 Philana Ling Lin, Christopher B Ford, M Teresa Coleman, Amy J Myers, Richa Gawande et al. doi:10.1038/nm.3412 Understanding how Mycobacterium tuberculosis is controlled by the body, leading to active disease in only a small fraction of infected individuals, is important for developing medical interventions to prevent and manage disease. Lin et al. now show that infected macaques with active tuberculosis have some sterile granulomas, suggesting immune-mediated control at certain sites of infection. Insight into the mechanisms underlying the heterogeneity of mycobacterial killing may inform vaccine development. The clathrin adaptor Numb regulates intestinal cholesterol absorption through dynamic interaction with NPC1L1   pp80 - 86 Pei-Shan Li, Zhen-Yan Fu, Ying-Yu Zhang, Jin-Hui Zhang, Chen-Qi Xu et al. doi:10.1038/nm.3417 Bao-Liang Song and colleagues report that the clathrin adaptor Numb recognizes a peptide motif within the cholesterol transporter NPC1L1 upon cholesterol binding and thus facilitates dietary cholesterol uptake into the gut. Inhibition of this Numb-NPC1L1 interaction in mice reduces serum cholesterol levels and thus may be a therapeutic target to treat hypercholesterolemia in the clinic. Pharmacological and genomic profiling identifies NF-[kappa]B-targeted treatment strategies for mantle cell lymphoma   pp87 - 92 Rami Rahal, Mareike Frick, Rodrigo Romero, Joshua M Korn, Robert Kridel et al. doi:10.1038/nm.3435 A screen for compounds that may inhibit the growth of hematological malignancies reveals the specific dependence of some mantle cell lymphoma (MCL) cell lines on canonical or alternative NF-[kappa]B signaling. As also seen in patients, genetic alterations affecting alternative NF-[kappa]B signaling confer insensibility to ibrutinib, a compound that was recently approved for MCL treatment. This alternative signaling pathway underscores the need to tailor treatments to the specific driving pathways in each patient group. Technical Reports Top Magnetic resonance imaging of tumor glycolysis using hyperpolarized 13C-labeled glucose   pp93 - 97 Tiago B Rodrigues, Eva M Serrao, Brett W C Kennedy, De-En Hu, Mikko I Kettunen et al. doi:10.1038/nm.3416 One of the most likely substrates for metabolic imaging of response to treatment in cancer is glucose, but until now, using hyperpolarized 13C-labelled glucose has been problematic because of the short lifetime of the hyperpolarization in this molecule. Using [U-13C, U-2H]glucose, Tiago Rodrigues et al. now show that they are able to image its glycolytic conversion to lactate in two mouse tumor models in vivo, and that in one model, flux is markedly reduced after treatment with the chemotherapeutic drug etoposide. Direct assessment of hepatic mitochondrial oxidative and anaplerotic fluxes in humans using dynamic 13C magnetic resonance spectroscopy   pp98 - 102 Douglas E Befroy, Rachel J Perry, Nimit Jain, Sylvie Dufour, Gary W Cline et al. doi:10.1038/nm.3415 There are currently a paucity of approaches for the direct in vivo assessment of rates of hepatic mitochondrial oxidation and anaplerotic flux in humans. With this in mind, Douglas Befroy and colleagues have developed a new 13C-labeling strategy that they use in combination with 13C magnetic resonance spectroscopy, which should prove useful in determining the potential role of changes in hepatic mitochondrial fat oxidation in diseases such as nonalcoholic fatty liver disease and type 2 diabetes. Corrigendum Top Corrigendum: EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers   p103 Michela Garofalo, Giulia Romano, Gianpiero Di Leva, Gerard Nuovo, Young-Jun Jeon et al. doi:10.1038/nm.2577 Top Advertisement SciBX: Science-Business eXchange Collection on Brown Fat   This special collection from SciBX: Science-Business eXchange provides an overview of the state of affairs on brown fat from the scientific, business and regulatory perspectives.   Click here to access the Collection for free!   Sponsored by: Ember Therapeutics AstraZeneca   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

You have been sent this Table of Contents Alert because you have opted in to receive it. You can change or discontinue your e-mail alerts at any time, by modifying your preferences on your nature.com account at: www.nature.com/myaccount (You will need to log in to be recognised as a nature.com registrant) For further technical assistance, please contact our registration department For print subscription enquiries, please contact our subscription department For other enquiries, please contact our customer feedback department Nature Publishing Group | 75 Varick Street, 9th Floor | New York | NY 10013-1917 | USA Nature Publishing Group's worldwide offices: London - Paris - Munich - New Delhi - Tokyo - Melbourne San Diego - San Francisco - Washington - New York - Boston Macmillan Publishers Limited is a company incorporated in England and Wales under company number 785998 and whose registered office is located at Brunel Road, Houndmills, Basingstoke, Hampshire RG21 6XS. © 2014 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.