|  | | | | | Advertisement |  | Nature Medicine and Helmholtz Zentrum München present:
1st Annual Helmholtz-Nature Medicine Diabetes Conference
September 22-24, 2013
Residenz München
Munich, Germany
Click here for more information or to register for this conference today!  | | | | |
Advertisement | | Nature Genetics
Focus on iCOGS
Nature Genetics is pleased to present the iCOGS print and online Focus advancing our understanding of the genetic susceptibility to three common hormone-related cancers-breast, ovarian and prostate cancers. This collection of 13 papers by the COGS (Collaborative Oncological Gene-environment Study) Consortium is accompanied by editorial essays highlighting and analyzing the main themes of this milestone in genetic epidemiology.
View the Focus for FREE at:
www.nature.com/ng/focus/iCOGS
Produced with support from
Illumina | | | | | Nature Medicine Podcast |  Top | |  | | Viruses on the brain
We discuss why some brain cells are better virus fighters than others and how a problematic adjuvant explains the failure of some cancer vaccines.
Listen Now | | | Editorial | Top | | | | Of men, not mice p379
doi:10.1038/nm.3163
A recent study showing that mice do not reproduce the patterns of gene expression induced by human inflammatory disease has provoked renewed discussion of the validity of animal models in translational research. | | News | Top | | | | New, intensive trials planned on heels of Mississippi HIV 'cure' pp380 - 381
Elie Dolgin
doi:10.1038/nm0413-380 | | | | Competition intensifies over DNA-based tests for prenatal diagnoses p381
Kevin Jiang
doi:10.1038/nm0413-381 | | | | Manufacturers push the limits of megacombo vaccines for kids p382
Elie Dolgin
doi:10.1038/nm0413-382 | | | | New yardstick could speed access to cancer drugs for surgery p383
Sarah CP Williams
doi:10.1038/nm0413-383 | | | | Underestimate of HIV reservoirs threatens purging approach pp384 - 385
Elie Dolgin
doi:10.1038/nm0413-384 | | | | Regulatory agency struggles under the weight of genomic data p385
Yevgeniy Grigoryev
doi:10.1038/nm0413-385 | | | | Under scrutiny, India's medical research council faces review p386
Killugudi Jayaraman
doi:10.1038/nm0413-386a | | Correction | Top | | | | Corrections p386
doi:10.1038/nm0413-386b | | News | Top | | | | | Q&A | | | | Straight talk with...Miyoung Chun p387
doi:10.1038/nm0413-387
The Brain Activity Map is an initiative by the US National Institutes of Health to understand how thousands of neurons work in concert to control behavior and trigger disease. Miyoung Chun, vice president for science programs at The Kavli Foundation in Oxnard, California, has been developing the project since the beginning and is the self-described [ldquo]glue[rdquo] between its many diverse stakeholders. Chun spoke with Virginia Hughes about the evolution of the project. | | | | | News in Brief | | | | Biomedical briefing pp388 - 389
doi:10.1038/nm0413-388 | | | | | News Features | | | | Natural products emergent pp390 - 392
Daniel Grushkin
doi:10.1038/nm0413-390
Natural compounds produced by the world's microbes were once the go-to source of molecules for the drug industry before the chemistry dried up and big pharma went packing. Now, researchers hope that advances in genomics will bring companies back into the fold. Daniel Grushkin visits one startup hoping to accelerate the process. | | | | Natural-born scientists p392
Daniel Grushkin
doi:10.1038/nm0413-392 | | Book Review | Top | | | | Evaluating health care costs p393
Henry J. Aaron reviews The Cost Disease: Why Computers Get Cheaper and Health Care Doesn't by William J. Baumol
doi:10.1038/nm.3148 | | Correspondence | Top | | | | Circulating fetuin-A and free fatty acids interact to predict insulin resistance in humans pp394 - 395
Norbert Stefan and Hans-Ulrich Haring
doi:10.1038/nm.3116 | | | | Systematic reviews deserve more credit than they get pp395 - 396
Mohammed Toseef Ansari and David Moher
doi:10.1038/nm.3151 | | News and Views | Top | | | | Antigen depots: T cell traps? pp397 - 398
Sacha Gnjatic and Nina Bhardwaj
doi:10.1038/nm.3113
Although cancer vaccines can induce tumor-specific cytotoxic CD8+ T cells, tumors treated by vaccination often fail to regress. A study in mice provides a potential explanation for this phenomenon by showing that a peptide vaccine in a water-oil adjuvant leads to the trapping of tumor-specific CD8+ T cells at the vaccination site, instead of promoting an effective T cell response at the tumor site (pages 465-472).
See also: Article by Hailemichael et al. | | | | Exploring the erythroblastic island pp399 - 401
Merav Socolovsky
doi:10.1038/nm.3156
Two new studies suggest a crucial role for macrophages in boosting the number of red blood cells produced in vivo during stress, with translational implications for disease states such as [beta]-thalassemia and polycythemia vera (pages 429-436 and 437-445).
See also: Article by Chow et al. | Article by Ramos et al. | | | | Love the one you're with: the HIV, B cell and TFH cell triangle pp401 - 402
Shiv Pillai
doi:10.1038/nm.3141
Many HIV-infected people show impaired humoral immune responses, but it is unclear why. A new view into this conundrum may be provided with the recent discovery of altered interactions between follicular helper T (TFH) cells and germinal center B cells from HIV-infected individuals. This leads to inadequate TFH cell help for germinal center B cells and decreased B cell antibody responses (pages 494-499).
See also: Letter by Cubas et al. | | | | Blocking bleeding: reversing anticoagulant therapy pp402 - 404
Jack Ansell
doi:10.1038/nm.3157
A new generation of target-specific inhibitors of the coagulation enzymes thrombin and factor Xa has been approved for a number of indications, but the clinical use of these drugs is hindered by the lack of a way to reverse bleeding, should it occur. An antidote to these new oral anticoagulants has now been designed and shows promise in small-animal models of blood loss (pages 446-451).
See also: Article by Lu et al. | | | | Sorting receptors at Down's syndrome synapses pp404 - 406
Matt W Jones
doi:10.1038/nm.3152
Trisomy 21 triggers multiple potential routes to intellectual disability in Down's syndrome. A new study suggests that aberrant endosomal function may contribute to the neuronal deficits behind learning and memory impairments in affected individuals (pages 473-480).
See also: Article by Wang et al. | | | | Coagulation factor defends adenovirus from immune attack pp406 - 407
Glen R Nemerow
doi:10.1038/nm.3149
Adenovirus type 5 (Ad5) has been intensively studied as a viral vector for gene therapy, and understanding host-Ad5 interactions will be key to the safe and effective use of this vector. A recent study in mice provides new insights in this area by showing that Ad5 enlists a host coagulation factor to overcome complement-mediated blockade and infect the liver (pages 452-457).
See also: Article by Xu et al. | | | | Metabolic reprogramming in polycystic kidney disease pp407 - 409
Carmen Priolo and Elizabeth P Henske
doi:10.1038/nm.3140
A recent study shows that, like cancer cells, cells lacking the Pdk1 gene reprogram their metabolism to use aerobic glycolysis[mdash]the 'Warburg effect'. Targeting this pathway using a glucose analog that cannot be metabolized resulted in slower disease progression in mouse models of polycystic kidney disease. This work thus suggests a new potential therapeutic approach for autosomal dominant polycystic kidney disease (pages 488-493).
See also: Letter by Rowe et al. | | | | | | | Community Corner | Top | | | | Bettering BCG: a tough task for a TB vaccine? pp410 - 411
doi:10.1038/nm.3153 | | Between Bedside and Bench | Top | | | | Is heart regeneration on the right track? pp412 - 413
Christine L Mummery and Richard T Lee
doi:10.1038/nm.3158
Myocardial infarction can cause irreversible heart muscle cell damage and lingering cardiac problems that can eventually lead to heart failure. For over a decade, researchers have been trying to coax stem cells to differentiate into cardiomyocytes to repair damaged heart tissue, with limited success. In 'Bedside to Bench', Christine L. Mummery and Richard T. Lee lay out a framework for re-evaluating cardiac cell therapies in the context of two recent clinical trials, in which autologous cardiac stem cells derived from heart biopsies were transferred into patients, with promising, albeit difficult to interpret, results. Results from previous clinical trials using autologous bone marrow-derived adult stem cells to induce cardiac regeneration add to the debate about how to cautiously move forward in the cardiac regeneration field and to the questions that need to be urgently answered at the bench. In 'Bench to Bedside', Young-Jae Nam, Kunhua Song and Eric N. Olson discuss a number of recent studies in rodents showing that cardiac fibroblasts can be reprogrammed, via miRNAs and a transcription factor 'cocktail', to express cardiac genes, which resulted in improved cardiac function in the animals, suggesting a new way forward for fixing damaged heart tissue. | | | | Heart repair by cardiac reprogramming pp413 - 415
Young-Jae Nam, Kunhua Song and Eric N Olson
doi:10.1038/nm.3147 | | Research Highlights | Top | | | | HIV infections: Restricting HIV from macrophages | Infectious diseases: Clash of the interferons | Influenza virus: Endogenous lipids halt influenza | Autoimmune diseases: Salt spurs autoimmunity | Neurodevelopmental disorders: Synaptic supervision | Metabolism: A role for MHCII in immunometabolism | T cells: Cross-reactive memory | New from NPG | Brief Communication | Top | | | | Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co-therapy pp418 - 420
Feng Li, Jie Lu, Jie Cheng, Laiyou Wang, Tsutomu Matsubara, Ivan L Csanaky, Curtis D Klaassen, Frank J Gonzalez and Xiaochao Ma
doi:10.1038/nm.3104
Rifampicin and isoniazid are often used together as a co-therapy to treat tuberculosis, but their combined use often leads to hepatoxicity in humans. Xiaochao Ma and colleagues now report the mechanisms behind this side effect, thus opening a possible avenue to the safer use of these effective drugs. | | Articles | Top | | | | Preventive and therapeutic effects of Smad7 on radiation-induced oral mucositis pp421 - 428
Gangwen Han, Li Bian, Fulun Li, Ana Cotrim, Donna Wang, Jianbo Lu, Yu Deng, Gregory Bird, Anastasia Sowers, James B Mitchell, J Silvio Gutkind, Rui Zhao, David Raben, Peter ten Dijke, Yosef Refaeli, Qinghong Zhang and Xiao-Jing Wang
doi:10.1038/nm.3118
Ulcerations of the oral cavity, or oral mucositis, often occur during radiation treatment for cancers of the head or neck or during bone marrow transplantation. Xiao-Jing Wang and colleagues now show that in a mouse model, Smad7 is an effective treatment for this condition, offering more hope for its clinical management. | | | | CD169+ macrophages provide a niche promoting erythropoiesis under homeostasis and stress pp429 - 436
Andrew Chow, Matthew Huggins, Jalal Ahmed, Daigo Hashimoto, Daniel Lucas, Yuya Kunisaki, Sandra Pinho, Marylene Leboeuf, Clara Noizat, Nico van Rooijen, Masato Tanaka, Zhizhuang Joe Zhao, Aviv Bergman, Miriam Merad and Paul S Frenette
doi:10.1038/nm.3057
Chow et al. report a crucial role for macrophages in erythroblast development in mice. Under conditions that induce new red blood cell formation, macrophage depletion impaired red blood cell recovery. Conversely, macrophage depletion normalized red blood cell counts in a mouse model of polycythemia vera, pointing to a potential new therapeutic strategy for this disease. Findings similar to these are reported in an accompanying paper by Ramos et al.
See also: News and Views by Socolovsky | Article by Ramos et al. | | | | Macrophages support pathological erythropoiesis in polycythemia vera and [beta]-thalassemia pp437 - 445
Pedro Ramos, Carla Casu, Sara Gardenghi, Laura Breda, Bart J Crielaard, Ella Guy, Maria Franca Marongiu, Ritama Gupta, Ross L Levine, Omar Abdel-Wahab, Benjamin L Ebert, Nico Van Rooijen, Saghi Ghaffari, Robert W Grady, Patricia J Giardina and Stefano Rivella
doi:10.1038/nm.3126
Ramos et al. report a crucial role for macrophages in erythroblast development in mice. Under conditions that induce new red blood cell formation, macrophage depletion impaired red blood cell recovery. Conversely, macrophage depletion normalized red blood cell counts in mouse models of polycythemia vera and [reg]-thalassemia, pointing to a potential new therapeutic strategy for these diseases. Findings similar to these are reported in an accompanying paper by Chow et al.
See also: News and Views by Socolovsky | Article by Chow et al. | | | | A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa pp446 - 451
Genmin Lu, Francis R DeGuzman, Stanley J Hollenbach, Mark J Karbarz, Keith Abe, Gail Lee, Peng Luan, Athiwat Hutchaleelaha, Mayuko Inagaki, Pamela B Conley, David R Phillips and Uma Sinha
doi:10.1038/nm.3102
Coagulation factor Xa is targeted by a new generation of antithrombotic drugs such as rivaroxaban. However, as excessive factor Xa inhibition can cause bleeding, the clinical use of factor Xa inhibitors would be enhanced by the availability of a specific antidote. Uma Sinha and her colleagues devise such an antidote, an inactive form of recombinant factor Xa that can bind to and neutralize factor Xa inhibitors, and demonstrate its efficacy in animal models.
See also: News and Views by Ansell | | | | Coagulation factor X shields adenovirus type 5 from attack by natural antibodies and complement pp452 - 457
Zhili Xu, Qi Qiu, Jie Tian, Jeffrey S Smith, Gina M Conenello, Takashi Morita and Andrew P Byrnes
doi:10.1038/nm.3107
Understanding how adenoviruses transduce cells is important for their use and development as vaccine vectors. Adenovirus type 5 (Ad5) is known to bind coagulation factor X (FX), and FX is thought to act as a bridge between the virus and its receptor on hepatocytes. Andrew Byrnes and his colleagues now report that the major role of FX binding to Ad5 is actually to protect Ad5 from neutralization by complement and natural antibodies, and in the absence of B cells, Ad5 does not require FX binding for effective liver transduction.
See also: News and Views by Nemerow | | | | Differential innate immune response programs in neuronal subtypes determine susceptibility to infection in the brain by positive-stranded RNA viruses pp458 - 464
Hyelim Cho, Sean C Proll, Kristy J Szretter, Michael G Katze, Michael Gale Jr and Michael S Diamond
doi:10.1038/nm.3108
Different types of neurons are differentially susceptible to West Nile virus (WNV) infection. Michael Diamond and colleagues now show that cerebellar granule cell neurons (GCN) have a higher basal level of expression of type I interferon-inducible genes than cortical neurons, making GCN more resistant to infection by a variety of positive-stranded RNA viruses, including WNV. | | | | Persistent antigen at vaccination sites induces tumor-specific CD8+ T cell sequestration, dysfunction and deletion pp465 - 472
Yared Hailemichael, Zhimin Dai, Nina Jaffarzad, Yang Ye, Miguel A Medina, Xue-Fei Huang, Stephanie M Dorta-Estremera, Nathaniel R Greeley, Giovanni Nitti, Weiyi Peng, Chengwen Liu, Yanyan Lou, Zhiqiang Wang, Wencai Ma, Brian Rabinovich, Kimberly S Schluns, Richard E Davis, Patrick Hwu and Willem W Overwijk
doi:10.1038/nm.3105
Cancer vaccines have had limited success in eliminating tumors in patients. Here Willem Overwijk and colleagues report that one reason for the failure of peptide-based vaccines may be their formulation. Their research shows that peptides formulated in incomplete Freund's adjuvant sequester CD8+ T cells at the site of injection, leading to T cell dysfunction and eventual apoptosis. A peptide and adjuvant formulation that did not persist long term at the injection site showed superior ability to induce a functional antitumor T cell response.
See also: News and Views by Gnjatic & Bhardwaj | | | | Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction by modulating glutamate receptor recycling in Down's syndrome pp473 - 480
Xin Wang, Yingjun Zhao, Xiaofei Zhang, Hedieh Badie, Ying Zhou, Yangling Mu, Li Shen Loo, Lei Cai, Robert C Thompson, Bo Yang, Yaomin Chen, Peter F Johnson, Chengbiao Wu, Guojun Bu, William C Mobley, Dongxian Zhang, Fred H Gage, Barbara Ranscht, Yun-wu Zhang, Stuart A Lipton, Wanjin Hong and Huaxi Xu
doi:10.1038/nm.3117
Synaptic abnormalities and learning dysfunction are prominent characteristics of Down's syndrome. Now Huaxi Xu and colleagues show that expression of the protein SNX27 is reduced in Down's syndrome brains and that restoring its expression can ameliorate learning dysfunction in a mouse model of the disease.
See also: News and Views by Jones | | | | Focal segmental glomerulosclerosis is induced by microRNA-193a and its downregulation of WT1 pp481 - 487
Christoph A Gebeshuber, Christoph Kornauth, Lihua Dong, Ralph Sierig, Jost Seibler, Martina Reiss, Stefanie Tauber, Martin Bilban, Shijun Wang, Renate Kain, Georg A Bohmig, Marcus J Moeller, Hermann-Josef Grone, Christoph Englert, Javier Martinez and Dontscho Kerjaschki
doi:10.1038/nm.3142
Focal and segmental glomerulosclerosis, or renal scarring, is a debilitating disease. The identification of the molecular mechanisms of its initiation and progression has been limited, thus hampering the development of proper animal models. Dontscho Kerjaschki and his colleagues now report that microRNA-193a is elevated in human cases of the disease and that transgenic expression in mice is sufficient to cause the condition. | | Letters | Top | | | | Defective glucose metabolism in polycystic kidney disease identifies a new therapeutic strategy pp488 - 493
Isaline Rowe, Marco Chiaravalli, Valeria Mannella, Valeria Ulisse, Giacomo Quilici, Monika Pema, Xuewen W Song, Hangxue Xu, Silvia Mari, Feng Qian, York Pei, Giovanna Musco and Alessandra Boletta
doi:10.1038/nm.3092
Polycystic kidney disease is marked by progressive growth of renal tubular epithelia and thus the formation of pathological cysts in the organ over time. Alessandra Boletta and her colleagues now show that this cystic growth has the hallmarks of the Warburg effect (that is, the primary reliance of cells on glycolysis for their energy demands) and that blocking this effect in vivo is sufficient to improve disease progression in two mouse models.
See also: News and Views by Priolo & Henske | | | | Inadequate T follicular cell help impairs B cell immunity during HIV infection pp494 - 499
Rafael A Cubas, Joseph C Mudd, Anne-Laure Savoye, Matthieu Perreau, Julien van Grevenynghe, Talibah Metcalf, Elizabeth Connick, Amie Meditz, Gordon J Freeman, Guillermo Abesada-Terk Jr, Jeffrey M Jacobson, Ari D Brooks, Shane Crotty, Jacob D Estes, Giuseppe Pantaleo, Michael M Lederman and Elias K Haddad
doi:10.1038/nm.3109
B cell responses are impaired in HIV-infected individuals. Elias Haddad and colleagues now report that follicular helper T (TFH) cells, which are crucial for the maturation of B cell memory and development of high-affinity antibodies, are functionally impaired upon interaction with lymph node germinal center B cells from HIV-infected individuals. The interaction of the inhibitory molecule PD-1 on TFH cells with its ligand PD-L1, which is elevated on germinal center B cells in HIV-infected lymph nodes, impairs TFH cell proliferation and antibody production by B cells, thus providing insight into humoral dysfunction in HIV infection.
See also: News and Views by Pillai | | Technical Report | Top | | | | Enhanced detection of myeloperoxidase activity in deep tissues through luminescent excitation of near-infrared nanoparticles pp500 - 505
Ning Zhang, Kevin P Francis, Arun Prakash and Daniel Ansaldi
doi:10.1038/nm.3110
The noninvasive detection of myeloperoxidase (MPO)-mediated oxidative stress in deep tissue inflammatory foci has been hampered by poor penetration of luminol-emitted short wavelength light due to tissue absorption and scattering. To circumvent this, Daniel Ansaldi and his colleagues have adopted a chemiluminescence resonance energy transfer approach whereby near-infrared (NIR) nanoparticles are used to red-shift luminol-emitted blue light to the NIR. Improved in vivo detectability of MPO is demonstrated in a lipopolysaccharide-induced pulmonary inflammation model, as well as in deep tissue tumor metastases. | | | Top | |  | | | | | | | 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 | | | | | | | | |
No comments:
Post a Comment