Nature Medicine Contents: December 2011 Volume 17 Number 12 pp 1523-1693

Advertisement New books from CSHL Press! •Angiogenesis: Biology and Pathology reviews angiogenic mechanisms in normal development and diseases such as cancer. •The Biology of Alzheimer Disease examines our molecular understanding of the disease and potential therapeutic agents. •HIV: From Biology to Prevention and Treatment covers everything from HIV pathogenesis to prevention. TABLE OF CONTENTS December 2011 Volume 17, Issue 12 Editorial News Book Review Correspondence News and Views Community Corner Between Bedside and Bench Research Highlights Commentary Review Articles Letters Technical Reports Addenda Corrigenda Advertisement Try our ELISA kits risk-free!  RayBio® ELISA kits now come with a 90-day, 100% satisfaction guarantee. Choose from over 650 ELISA kits detecting human, mouse, rat, porcine, bovine, equine, canine, feline, non-human primate or cotton rat proteins. Recommend to your library Web feed Available online only Subscribe Advertisement Change the face of human health Research professionals know translational medicine is at best a difficult path; and at its worst an intractable quagmire. The Eureka Institute is here to help you on your journey through building bridges and catalyzing change. Over one week in Sicily, you'll encounter interactive lectures, intense personal mentoring and educators dedicated to cultivating you and your career. Find out more: http://www.eurekainstitute.org/   Nature Medicine Podcast  Top Trash talk  Inhibiting the cell's garbage collection system provides a potential new cancer therapy and a new probe can image blocked arteries in exquisite detail. Listen Now Editorial Top Reaction to retractions p1523 doi:10.1038/nm.2611 Retracting a paper is perhaps the most unpleasant task a journal has to face, particularly if the retraction involves scientific misconduct. With the number of retractions on the rise, an improved mechanism to deal with misconduct is necessary. Full Text | PDF News Top Trial networks move beyond single-disease strategies p1525 Elie Dolgin doi:10.1038/nm1211-1525 Full Text | PDF New HCV drugs trigger race for more tolerable therapies p1526 Sarah C P Williams doi:10.1038/nm1211-1526 Full Text | PDF Institutes unite to put New York on the biopharma map p1527 Hannah Waters doi:10.1038/nm1211-1527 Full Text | PDF Four-in-one HIV pill may be exception among combination drugs pp1528 - 1529 Hannah Waters doi:10.1038/nm1211-1528a Full Text | PDF Class of once-weekly diabetes drugs poised for approval p1528 Hannah Waters doi:10.1038/nm1211-1528b Full Text | PDF Patent-sharing scheme for neglected diseases may have catch p1529 Hannah Waters doi:10.1038/nm1211-1529a Full Text | PDF Corrections p1529 doi:10.1038/nm1211-1529b Full Text | PDF International coding upgrade affects clinical research and reviews p1530 Madhumita Venkataramanan doi:10.1038/nm1211-1530 Full Text | PDF Databases aim to bridge the East-West divide of drug discovery p1531 Katharine Sanderson doi:10.1038/nm1211-1531a Full Text | PDF Biostatisticians call for more scientifically rigorous pilot studies p1531 Cassandra Willyard doi:10.1038/nm1211-1531b Full Text | PDF News in brief: Biomedical briefing pp1532 - 1533 doi:10.1038/nm1211-1532 Full Text | PDF Q&A Straight talk with... Amanda Glassman  p1534 Elie Dolgin doi:10.1038/nm1211-1534 Since its launch in 2001, the Center for Global Development (CGD) has been instrumental in convening working groups and issuing reports that shape the agenda for a range of topics that affect global poverty and people of the developing world. At the helm of its global health effort is Amanda Glassman. In recognition of CGD's ten-year anniversary last month, Elie Dolgin spoke to Glassman about how the think tank turns its words into actions. Abstract | Full Text | PDF Opinion Efficient drug approval and monitoring must rely on sound regulatory science p1535 Emma A Meagher and Garret A FitzGerald doi:10.1038/nm1211-1535 The path to drug approval is long, hard and often perplexing. In recent months, the US Food and Drug Administration (FDA) has promised to bolster 'regulatory science', which aims to transform its decision-making process to be more efficient, transparent and accountable. However, diverse stakeholders, including patients, drug developers and the US Congress, will have to rise to the challenge of coordinating their priorities if this endeavor is to succeed. Full Text | PDF News Features Breaking the silence pp1536 - 1538 Alla Katsnelson doi:10.1038/nm1211-1536 Scientists had long assumed that any genetic mutation that does not alter a protein sequence should have no impact on human health. But recent research has shown that such synonymous DNA changes can trigger disease in a number of ways. Alla Katsnelson talks to scientists and biotech companies who are speaking up about 'silent' mutations. Full Text | PDF 2011 in review p1539 doi:10.1038/nm1211-1539a Full Text | PDF The Yearbook p1539 doi:10.1038/nm1211-1539b We list key people who made headlines this year, either by standing up for what they saw as right or by stopping what they felt was wrong. Full Text | PDF Notable advances 2011 pp1540 - 1541 doi:10.1038/nm1211-1540 We look back on some of the key insights into biomedicine published this year. Full Text | PDF Drugs in traffic: the road to approval pp1542 - 1543 doi:10.1038/nm1211-1542 Here we present the in-gene-ious cancer drugs, sanguine blood thinners and others of 2011 as we look back on this year's major headlines related to medications. Full Text | PDF Timeline of events: A brief history of what made news this year p1543 doi:10.1038/nm1211-1543 Full Text | PDF A retrospective of retractions: the striking record in 2011 p1544 doi:10.1038/nm1211-1544 Full Text | PDF Book Review Top The history of hemophilia p1545 Katherine A High reviews The Bleeding Disease: Hemophilia and the Unintended Consequences of Medical Progress by Stephen Pemberton doi:10.1038/nm.2585 Full Text | PDF Correspondence Top Mannose-binding lectin[mdash]the forgotten molecule? pp1547 - 1548 Michael Osthoff, George Trendelenburg, Damon P Eisen and Marten Trendelenburg doi:10.1038/nm.2588 Full Text | PDF Reply to: Mannose-binding lectin[mdash]the forgotten molecule? p1548 Costantino Iadecola and Josef Anrather doi:10.1038/nm.2589 Full Text | PDF News and Views Top A gut triumvirate rules homeostasis pp1549 - 1550 Alejo Chorny and Andrea Cerutti doi:10.1038/nm.2592 IgA regulates intestinal homeostasis by maintaining appropriate communities of bacteria within the gut. A new study shows that intestinal bacteria regulate metabolism via IgA (pages 1585-1593). Full Text | PDF See also: Article by Shulzhenko et al. A sweet T cell response pp1551 - 1552 Rino Rappuoli and Ennio De Gregorio doi:10.1038/nm.2587 Although protein-polysaccharide conjugate vaccines provide notable clinical benefits, it is still not fully understood how they work. A new mechanism of action for these vaccines has been identified in which T cells can recognize sugar epitopes in the context of the major histocompatibility complex (MHC) provided they are bound to a protein 'anchor', which allows binding of the sugar epitope to the MHC (pages 1602-1609). Full Text | PDF See also: Article by Avci et al. Stressed tumor cell, chemosensitized cancer pp1552 - 1554 Erik A C Wiemer doi:10.1038/nm.2593 miR-200 family expression results in highly proliferative ovarian cancer cells. Yet this expression is also linked to longer overall survival in women with ovarian cancer. A new study sheds light into this apparent paradox showing that two members of this family[mdash]miR-141 and miR-200a[mdash]not only boost tumor growth but also sensitize tumor cells to chemotherapy (pages 1627-1635). Full Text | PDF See also: Article by Mateescu et al. NF-[kappa]B in DCs: it takes effort to be immature pp1554 - 1556 Remi J Creusot doi:10.1038/nm.2586 The nuclear factor-[kappa]B (NF-[kappa]B) family of regulators is well known for mediating dendritic cell (DC) maturation[mdash]that is, the acquisition of the functions required for full activation of T cells. Paradoxically, a key member of this family, NF-[kappa]B1, is now also implicated in maintaining DCs in an immature state (pages 1663-1667). Full Text | PDF See also: Letter by Dissanayake et al. Nitrite-NO bailout for a NOS complex too big to fail pp1556 - 1557 Mark T Gladwin and Jesus Tejero doi:10.1038/nm.2591 Cellular production of nitric oxide (NO) by nitric oxide synthase (NOS) in the face of limiting pools of arginine requires the intracellular citrulline-to-NO pathway, catalyzed by the enzyme argininosuccinate lyase (ASL). People with the urea cycle disorder argininosuccinic aciduria, caused by a deficiency of ASL, have systemic NO deficiency, which can be rescued by the use of an alternative, NOS-independent, nitrite-to-NO pathway. Full Text | PDF See also: Article by Erez et al. Diagnosis in a dish: your skin can help your brain pp1558 - 1559 Anita Huttner and Pasko Rakic doi:10.1038/nm.2599 The discovery that skin cells from an adult human can be reprogrammed back to their embryonic stage and then differentiated to produce neuron-like cells in culture opens an opportunity to study disease pathogenesis and screen potential therapeutic drugs. A new study provides an example of this approach for the neuropsychiatric disorder Timothy syndrome (pages 1657-1662). Full Text | PDF See also: Letter by Pasca et al. Nature Medicine JOBS of the week Post doc position at the Institute of Biomedicine, University of Eastern Finland University of Eastern Finland W2 - Professorship of Theory and Practice of Clinical Care The University of Applied Sciences in Saarland Mechanical Technician CERN - European ORganization for Nuclear Research Job opening in stem cell research for Experienced researcher BioTalentum Ltd. More Science jobs from Nature Medicine EVENT Up Close and Personalized, International Congress on Personalized Medicine 02.-05.02.12 Florence, Italy More science events from Community Corner Top Mixed results for a malaria vaccine pp1560 - 1561 doi:10.1038/nm1211-1560 Full Text | PDF Between Bedside and Bench Top Fruitful progress to fertility: Preserving oocytes from chemodestruction pp1562 - 1563 Min Xu, Mary Ellen Pavone and Teresa Woodruff doi:10.1038/nm.2595 Chemotherapy can save the lives of many individuals with cancer. Unfortunately, it usually causes infertility after treatment, posing a concern for these people who will face a lifetime condition that considerably limits the quality of their lives. Advances in the field of oncofertility have brought hope to cancer survivors who long to plan a family; however, standard approaches only rely on cryopreservation of sperms and eggs before treatment and do not prevent infertility. In 'Bedside to Bench', Min Xu, Mary Ellen Pavone and Teresa Woodruff examine a study where individuals treated with gonadotropin-releasing hormone (GnRH) agonists before cancer therapy showed a decreased risk of infertility. How these agonists work to suppress and protect ovarian function and increase fertility in women after treatment is still unclear and begs further investigation at the bench. In 'Bench to Bedside', Amander Clark, Bart Phillips and Kyle Orwig discuss potential experimental options to preserve and restore male fertility after chemotherapy. These approaches will shed light into mechanisms of male fertility and spermatogenesis and may be the alternative to sperm freezing, which is not suitable for prepubertal boys and men unable to make sperm. Full Text | PDF Fruitful progress to fertility: Male fertility in the test tube pp1564 - 1565 Amander T Clark, Bart T Phillips and Kyle E Orwig doi:10.1038/nm.2594 Full Text | PDF Research Highlights Top Autoimmunity: Defects in DC tolerance | Addiction: One thing leads to another | Immunotherapy: A safety switch for immunotherapy | Neurological disorders: Serine to the rescue Commentary Top Improving the efficacy of translational medicine by optimally integrating health care, academia and industry pp1567 - 1569 Stefan R Bornstein and Julio Licinio doi:10.1038/nm.2583 Full Text | PDF Review Top Diseases in a dish: modeling human genetic disorders using induced pluripotent cells pp1570 - 1576 Gustavo Tiscornia, Erica Lorenzo Vivas and Juan Carlos Izpisua Belmonte doi:10.1038/nm.2504 This review provides a guide to the conceptual and practical issues to consider when trying to generate an iPSc model that accurately recapitulates the features of a human genetic disease. The authors highlight recent successes in modeling genetic diseases using iPSCs and offers a perspective on the next steps that will be needed to improve current iPSC-based disease models. Abstract | Full Text | PDF Articles Top A hepatocyte growth factor receptor (Met)-insulin receptor hybrid governs hepatic glucose metabolism pp1577 - 1584 Arlee Fafalios, Jihong Ma, Xinping Tan, John Stoops, Jianhua Luo, Marie C DeFrances and Reza Zarnegar doi:10.1038/nm.2531 It is well regarded that insulin receptor signaling in the liver is key to proper metabolic control. Reza Zarnegar and his colleagues now show that the hepatocyte growth factor receptor, Met, physically interacts with the insulin receptor signaling complex, potentiating the latter's signaling. They also show that Met signaling restores insulin responsiveness in a mouse model of insulin resistance, suggesting a potentially new therapeutic avenue to treat prediabetes. Abstract | Full Text | PDF Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut pp1585 - 1593 Natalia Shulzhenko, Andrey Morgun, William Hsiao, Michele Battle, Michael Yao, Oksana Gavrilova, Marlene Orandle, Lloyd Mayer, Andrew J Macpherson, Kathy D McCoy, Claire Fraser-Liggett and Polly Matzinger doi:10.1038/nm.2505 Polly Matzinger and her colleagues have shown that in the absence of B cells, and in the presence of the microbiota, the intestinal epithelium launches its own immune defense mechanisms. However, this comes at the expense of metabolic programs involved in fat absorption by the gut. These results could explain the lipid malabsorption often seen in humans with common variable immunodeficiency or with HIV infection. Abstract | Full Text | PDF See also: News and Views by Chorny & Cerutti Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-[gamma] and TNF-[alpha] pp1594 - 1601 Yi Liu, Lei Wang, Takashi Kikuiri, Kentaro Akiyama, Chider Chen, Xingtian Xu, Ruili Yang, WanJun Chen, Songlin Wang and Songtao Shi doi:10.1038/nm.2542 Bone marrow-derived mesenchymal stem cells (BMMSCs) have so far failed to live up to their potential as a treatment for the repair of large bone defects. Songtao Shi and his colleagues now show that this may be due to their apoptosis mediated by resident T cells in the wound as a result of excess IFN-[gamma] and TNF-[alpha] signaling. They show that reducing the levels of these cytokines, including through the local administration of aspirin, markedly increases the survival of implanted BMMSCs and improves bone wound healing in a mouse model. Abstract | Full Text | PDF A mechanism for glycoconjugate vaccine activation of the adaptive immune system and its implications for vaccine design pp1602 - 1609 Fikri Y Avci, Xiangming Li, Moriya Tsuji and Dennis L Kasper doi:10.1038/nm.2535 Glycoconjugate vaccines[mdash]such as those targeting some bacteria[mdash]couple a glycan to a protein to provide T cell help to B cells and induce polysaccharide-specific IgGs. T cell help has been thought to be conferred by recognition of the protein portion by T cells. Dennis Kasper and his colleagues now report that a glycan-peptide conjugate can induce T cells specific for the glycan moiety, which could help inform future glycoconjugate vaccine development. Abstract | Full Text | PDF See also: News and Views by Rappuoli & De Gregorio Oxidation of CaMKII determines the cardiotoxic effects of aldosterone pp1610 - 1618 B Julie He, Mei-ling A Joiner, Madhu V Singh, Elizabeth D Luczak, Paari Dominic Swaminathan, Olha M Koval, William Kutschke, Chantal Allamargot, Jinying Yang, Xiaoqun Guan, Kathy Zimmerman, Isabella M Grumbach, Robert M Weiss, Douglas R Spitz, Curt D Sigmund, W Matthijs Blankesteijn, Stephane Heymans, Peter J Mohler and Mark E Anderson doi:10.1038/nm.2506 The hormone aldosterone can damage the heart after myocardial infarction, such that drugs that inhibit its action are often prescribed. B. Julie He et al. now uncover a new pathway underlying the detrimental effects of aldosterone action: oxidation of the enzyme Ca2+/calmodulin-dependent protein kinase II leads to its activation and increased expression of the metalloprotease MMP9 in cardiac muscle cells, thereby promoting cardiac rupture. Abstract | Full Text | PDF Requirement of argininosuccinate lyase for systemic nitric oxide production pp1619 - 1626 Ayelet Erez, Sandesh C S Nagamani, Oleg A Shchelochkov, Muralidhar H Premkumar, Philippe M Campeau, Yuqing Chen, Harsha K Garg, Li Li, Asad Mian, Terry K Bertin, Jennifer O Black, Heng Zeng, Yaoping Tang, Anilkumar K Reddy, Marshall Summar, William E O'Brien, David G Harrison, William E Mitch, Juan C Marini, Judy L Aschner, Nathan S Bryan and Brendan Lee doi:10.1038/nm.2544 The enzyme argininosuccinate lyase (ASL) generates the amino acid arginine, the precursor to both urea and nitric oxide. However, arginine supplementation is not sufficient to correct all of the symptoms of individuals with a congenital deficiency of this enzyme. Ayelet Erez et al. explain this paradox by showing that ASL has a role in nitric oxide synthesis that is independent of its catalytic activity and provide evidence that therapy with agents boosting nitric oxide levels might be beneficial in ASL-deficient individuals. Abstract | Full Text | PDF See also: News and Views by Gladwin & Tejero miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response pp1627 - 1635 Bogdan Mateescu, Luciana Batista, Melissa Cardon, Tina Gruosso, Yvan de Feraudy, Odette Mariani, Andre Nicolas, Jean-Philippe Meyniel, Paul Cottu, Xavier Sastre-Garau and Fatima Mechta-Grigoriou doi:10.1038/nm.2512 This report identifies a new contribution of members of the miR-200 family to tumorigenesis. miR-200a and miR-141 specifically regulate p38[alpha], contributing to the cellular modulation of oxidative stress responses. In this role, the miRs can accelerate ovarian tumorigenesis but also endow cancer cells with increased sensitivity to ROS-inducing chemotherapy. This two-part effect is reflected on the distinct association of the miRs with patient survival and may be informative for treatment decisions. Abstract | Full Text | PDF See also: News and Views by Wiemer Letters Top Inhibition of proteasome deubiquitinating activity as a new cancer therapy pp1636 - 1640 Padraig D'Arcy, Slavica Brnjic, Maria Hagg Olofsson, Marten Fryknas, Kristina Lindsten, Michelandrea De Cesare, Paola Perego, Behnam Sadeghi, Moustapha Hassan, Rolf Larsson and Stig Linder doi:10.1038/nm.2536 b-AP15 is a novel inhibitor of proteasome activity, with a different mechanism of action than the available and widely used proteasome inhibitors such as bortezomib. b-AP15 inhibits the deubiquitinating activity of the regulatory subunit of the proteasome, necessary for protein degradation, and induces cytotoxicity impairing tumor growth in mouse models. The compound may represent an alternative therapeutic approach with a broader spectrum of applicability than current proteasome inhibitors. First paragraph | Full Text | PDF A MEK-independent role for CRAF in mitosis and tumor progression pp1641 - 1645 Ainhoa Mielgo, Laetitia Seguin, Miller Huang, Maria Fernanda Camargo, Sudarshan Anand, Aleksandra Franovic, Sara M Weis, Sunil J Advani, Eric A Murphy and David A Cheresh doi:10.1038/nm.2464 Raf kinase activity is deregulated in cancers and is thought to promote tumor growth by inducing proliferation signaling through MEK/Erk. This report identifies a new role for c-Raf independent of MEK/Erk and relying on phosphorylation of Ser338. Phospho-C-Raf interacts with the mitotic kinases Aurora-A and Plk1, activating the latter to promote mitotic progression and increase cell division, and this pathway is a crucial mediator for the protumorigenic effect of c-Raf in vivo. First paragraph | Full Text | PDF Functionally recurrent rearrangements of the MAST kinase and Notch gene families in breast cancer pp1646 - 1651 Dan R Robinson, Shanker Kalyana-Sundaram, Yi-Mi Wu, Sunita Shankar, Xuhong Cao, Bushra Ateeq, Irfan A Asangani, Matthew Iyer, Christopher A Maher, Catherine S Grasso, Robert J Lonigro, Michael Quist, Javed Siddiqui, Rohit Mehra, Xiaojun Jing, Thomas J Giordano, Michael S Sabel, Celina G Kleer, Nallasivam Palanisamy, Rachael Natrajan, Maryou B Lambros, Jorge S Reis-Filho, Chandan Kumar-Sinha and Arul M Chinnaiyan doi:10.1038/nm.2580 This report identifies oncogenic fusions in individuals with breast cancer involving the genes encoding NOTCH and MAST, recurring in approximately 5-7% of studied cases. The fusions show growth-promoting properties that suggest that they may represent targetable events in a subset of people with breast cancer. First paragraph | Full Text | PDF The effects of dexpramipexole (KNS-760704) in individuals with amyotrophic lateral sclerosis pp1652 - 1656 Merit Cudkowicz, Michael E Bozik, Evan W Ingersoll, Robert Miller, Hiroshi Mitsumoto, Jeremy Shefner, Dan H Moore, David Schoenfeld, James L Mather, Donald Archibald, Mary Sullivan, Craig Amburgey, Juliet Moritz and Valentin K Gribkoff doi:10.1038/nm.2579 Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily affects motor neurons. Now, Valentin Gribkoff and his colleagues show some preliminary evidence that the drug dexpramipexole may have clinical activity in a small placebo-controlled trial in patients with ALS. First paragraph | Full Text | PDF Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome pp1657 - 1662 Sergiu P Pasca, Thomas Portmann, Irina Voineagu, Masayuki Yazawa, Aleksandr Shcheglovitov, Anca M Pasca, Branden Cord, Theo D Palmer, Sachiko Chikahisa, Seiji Nishino, Jonathan A Bernstein, Joachim Hallmayer, Daniel H Geschwind and Ricardo E Dolmetsch doi:10.1038/nm.2576 Timothy syndrome is a neurodevelopmental disease that includes autism-like features. Using iPS-derived neurons from individuals with Timothy syndrome, Ricardo Dolmetsch and his colleagues identify changes in cortical neuron fate and neurotransmitter expression that may begin to explain the neural mechanisms that underlie this disorder. First paragraph | Full Text | PDF See also: News and Views by Huttner & Rakic Nuclear factor-[kappa]B1 controls the functional maturation of dendritic cells and prevents the activation of autoreactive T cells pp1663 - 1667 Dilan Dissanayake, Hakan Hall, Nancy Berg-Brown, Alisha R Elford, Sara R Hamilton, Kiichi Murakami, Leslie Summers Deluca, Jennifer L Gommerman and Pamela S Ohashi doi:10.1038/nm.2556 Although maturation of dendritic cells can drive autoimmune responses in mice, it remains unclear whether intrinsic factors hold dendritic cells in a resting state. Pamela Ohashi and her colleagues identify a repressive mechanism requiring expression of nuclear factor-[kappa]B1 in dendritic cells. Loss of nuclear factor-[kappa]B1 results in CD8+ T cell activation, TNF-[alpha] production and autoimmune diabetes in mice. First paragraph | Full Text | PDF See also: News and Views by Creusot Stimulating healthy tissue regeneration by targeting the 5-HT2B receptor in chronic liver disease pp1668 - 1673 Mohammad R Ebrahimkhani, Fiona Oakley, Lindsay B Murphy, Jelena Mann, Anna Moles, Maria J Perugorria, Elizabeth Ellis, Anne F Lakey, Alastair D Burt, Angela Douglass, Matthew C Wright, Steven A White, Fabrice Jaffre, Luc Maroteaux and Derek A Mann doi:10.1038/nm.2490 Wound healing involves a transient regeneration of tissue, but, if this process continues unabated, pathology occurs in the form of fibrosis, which can prevent normal organ function and even death. Derek Mann and his colleagues have found that serotonin-responsive profibrogenic hepatic stellate cells inhibit the growth of neighboring liver cells during the termination phase of liver injury. They also found that inhibiting serotonin signaling during established disease improved liver fibrosis in various mouse models of liver injury. First paragraph | Full Text | PDF Identification of a central role for complement in osteoarthritis pp1674 - 1679 Qian Wang, Andrew L Rozelle, Christin M Lepus, Carla R Scanzello, Jason J Song, D Meegan Larsen, James F Crish, Gurkan Bebek, Susan Y Ritter, Tamsin M Lindstrom, Inyong Hwang, Heidi H Wong, Leonardo Punzi, Angelo Encarnacion, Mehrdad Shamloo, Stuart B Goodman, Tony Wyss-Coray, Steven R Goldring, Nirmal K Banda, Joshua M Thurman, Reuben Gobezie, Mary K Crow, V Michael Holers, David M Lee and William H Robinson doi:10.1038/nm.2543 Osteoarthritis, the breakdown of cartilage in synovial joints, has long been viewed as the result of 'wear and tear', but this report shows that dysregulation of the complement system has an active role in the pathogenesis of this disease. First paragraph | Full Text | PDF Technical Reports Top Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo  pp1680 - 1684 Hongki Yoo, Jin Won Kim, Milen Shishkov, Eman Namati, Theodore Morse, Roman Shubochkin, Jason R McCarthy, Vasilis Ntziachristos, Brett E Bouma, Farouc A Jaffer and Guillermo J Tearney doi:10.1038/nm.2555 The future of imaging is the integration of function and anatomy. Hongki Yoo et al. have successfully done just that by combining two existing intravascular imaging techniques into a single catheter-based system. Their dual-modality intra-arterial catheter uses a combination of optical frequency domain imaging and near-infrared fluorescence imaging to simultaneously provide molecular information in the context of the surrounding three-dimensional microanatomy of the artery wall. Abstract | Full Text | PDF Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules pp1685 - 1691 Makoto Mitsunaga, Mikako Ogawa, Nobuyuki Kosaka, Lauren T Rosenblum, Peter L Choyke and Hisataka Kobayashi doi:10.1038/nm.2554 Makoto Mitsunaga et al. have developed a new form of molecular-targeted cancer therapy that provides an alternative to current photodynamic approaches where damage to surrounding healthy cells and tissues can be a problem. They use a target-specific photosensitizer based on a near-infrared phthalocyanine dye, which is conjugated to monoclonal antibodies targeting human epidermal growth factor receptors (HER1 and HER2). Selective treatment using this approach was shown in vivo in subcutaneous cancer xenografts in mice. Abstract | Full Text | PDF Addenda Top Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge p1692 Scott G Hansen, Cassandra Vieville, Nathan Whizin, Lia Coyne-Johnson, Don C Siess, Derek D Drummond, Alfred W Legasse, Michael K Axthelm, Kelli Oswald, Charles M Trubey, Michael Piatak Jr, Jeffrey D Lifson, Jay A Nelson, Michael A Jarvis and Louis J Picker doi:10.1038/nm1211-1692 Full Text | PDF The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2  p1693 Baofeng Yang, Huixian Lin, Jiening Xiao, Yanjie Lu, Xiaobin Luo, Baoxin Li, Ying Zhang, Chaoqian Xu, Yunlong Bai, Huizhen Wang, Guohao Chen and Zhiguo Wang doi:10.1038/nm1211-1693a Full Text | PDF Corrigenda Top The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2  p1693 Baofeng Yang, Huixian Lin, Jiening Xiao, Yanjie Lu, Xiaobin Luo, Baoxin Li, Ying Zhang, Chaoqian Xu, Yunlong Bai, Huizhen Wang, Guohao Chen and Zhiguo Wang doi:10.1038/nm1211-1693b Full Text | PDF Targeting osteoclast-osteoblast communication p1693 Xu Cao doi:10.1038/nm1211-1693c Full Text | PDF Resolving controversies on the path to Alzheimer's therapeutics p1693 Dennis J Selkoe doi:10.1038/nm1211-1693d Full Text | PDF Top Advertisement Nature Outlook: Allergies The increased prevalence of allergies and asthma, especially in the developed world, has raised the stakes in the quest for prevention and cure. 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