NATURE MEDICINE
Nature Medicine is a biomedical research journal devoted to publishing the latest and most exciting advances in biomedical research for scientists and physicians, with an emphasis on clarity of presentation. Articles cover fields such as cancer biology, cardiovascular research, gene therapy, immunology, vaccine development, and neuroscience, aiming to keep Ph.D. and M.D. readers informed of a wide range of biomedical research findings. Original research articles published in Nature Medicine range from basic findings that have clear implications for disease pathogenesis and therapy to the earliest phases of human investigation, and are submitted from research groups at universities, independent research institutions, and biotechnology and pharmaceutical industries world-wide. As a cross-disciplinary journal at the heart of the international biomedical research community, Nature Medicine publishes the most relevant original research articles, news, and commentary that form the foundations of tomorrow's medicine.
 Nature Medicine Small interfering RNA?mediated xCT silencing in gliomas inhibits neurodegeneration and alleviates brain edema Neurodegeneration and brain edema are hallmarks of human malignant brain tumors. Here we show that genetic or pharmacological inhibition of the glutamate transporter xCT (Xc? system, encoded by SLC7a11) in vivo leads to abrogated neurodegeneration, attenuated perifocal edema and prolonged survival. These results show a crucial role for xCT in glioma-induced neurodegeneration and brain edema, corroborating the concept that edema formation may be in part a consequence of peritumoral cell death. Lewy body?like pathology in long-term embryonic nigral transplants in Parkinson's disease Fourteen years after transplantation into the striatum of an individual with Parkinson's disease, grafted nigral neurons were found to have Lewy body?like inclusions that stained positively for ?-synuclein and ubiquitin and to have reduced immunostaining for dopamine transporter. These pathological changes suggest that Parkinson's disease is an ongoing process that can affect grafted cells in the striatum in a manner similar to host dopamine neurons in the substantia nigra. These findings have implications for cell-based therapies and for understanding the cause of Parkinson's disease. Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation Two subjects with Parkinson's disease who had long-term survival of transplanted fetal mesencephalic dopaminergic neurons (11?16 years) developed ?-synuclein?positive Lewy bodies in grafted neurons. Our observation has key implications for understanding Parkinson's pathogenesis by providing the first evidence, to our knowledge, that the disease can propagate from host to graft cells. However, available data suggest that the majority of grafted cells are functionally unimpaired after a decade, and recipients can still experience long-term symptomatic relief. Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 years Postmortem analysis of five subjects with Parkinson's disease 9?14 years after transplantation of fetal midbrain cell suspensions revealed surviving grafts that included dopamine and serotonin neurons without pathology. These findings are important for the understanding of the etiopathogenesis of midbrain dopamine neuron degeneration and future use of cell replacement therapies. Activation of c-Kit in dendritic cells regulates T helper cell differentiation and allergic asthma Functional roles for C5a receptors in sepsis Stromal gene expression predicts clinical outcome in breast cancer CD3-specific antibody?induced immune tolerance involves transforming growth factor-? from phagocytes digesting apoptotic T cells Inhibition of pulmonary antibacterial defense by interferon-? during recovery from influenza infection Drug-induced cure drives conversion to a stable and protective CD8+ T central memory response in chronic Chagas disease A GRK5 polymorphism that inhibits ?-adrenergic receptor signaling is protective in heart failure Mast cell activators: a new class of highly effective vaccine adjuvants The anaplastic lymphoma kinase is an effective oncoantigen for lymphoma vaccination An ideal vaccination strategy against tumors relies on specific antigens that are required for tumor maintenance. For lymphoma, vaccination with subject-specific immunoglobulin idiotypes has had the most promising results. Here we show that DNA vaccination with plasmids encoding portions of the cytoplasmic domain of anaplastic lymphoma kinase (ALK), which has been translocated in different fusion proteins necessary for the growth of anaplastic large cell lymphoma (ALCL), protects mice from local and systemic lymphoma growth. The protection is potent and long lasting and elicits ALK-specific interferon-? responses and CD8+ T cell?mediated cytotoxicity. A combination of chemotherapy and vaccination significantly enhanced the survival of mice challenged with ALK+ lymphomas. These findings indicate that ALK represents an ideal tumor antigen for vaccination-based therapies of ALCL and possibly other ALK+ human tumors. Replacing PCR with COLD-PCR enriches variant DNA sequences and redefines the sensitivity of genetic testing PCR is widely employed as the initial DNA amplification step for genetic testing. However, a key limitation of PCR-based methods is the inability to selectively amplify low levels of mutations in a wild-type background. As a result, downstream assays are limited in their ability to identify subtle genetic changes that can have a profound impact in clinical decision-making and outcome. Here we describe co-amplification at lower denaturation temperature PCR (COLD-PCR), a novel form of PCR that amplifies minority alleles selectively from mixtures of wild-type and mutation-containing sequences irrespective of the mutation type or position on the sequence. We replaced regular PCR with COLD-PCR before sequencing or genotyping assays to improve mutation detection sensitivity by up to 100-fold and identified new mutations in the genes encoding p53, KRAS and epidermal growth factor in heterogeneous cancer samples that had been missed by the currently used methods. For clinically relevant microdeletions, COLD-PCR enabled exclusive amplification and isolation of the mutants. COLD-PCR will transform the capabilities of PCR-based genetic testing, including applications in cancer, infectious diseases and prenatal identification of fetal alleles in maternal blood. Noninvasive in vivo imaging of pancreatic islet cell biology Advanced imaging techniques have become a valuable tool in the study of complex biological processes at the cellular level in biomedical research. Here, we introduce a new technical platform for noninvasive in vivo fluorescence imaging of pancreatic islets using the anterior chamber of the eye as a natural body window. Islets transplanted into the mouse eye engrafted on the iris, became vascularized, retained cellular composition, responded to stimulation and reverted diabetes. Laser-scanning microscopy allowed repetitive in vivo imaging of islet vascularization, beta cell function and death at cellular resolution. Our results thus establish the basis for noninvasive in vivo investigations of complex cellular processes, like beta cell stimulus-response coupling, which can be performed longitudinally under both physiological and pathological conditions. More Web Site Traffic |
