abstract：:Retinoic acid and arsenic trioxide target the protein stability and transcriptional repression activity of the fusion oncoprotein PML-RARA, resulting in regression of acute promyelocytic leukemia (APL). Phenotypically, retinoic acid induces differentiation of APL cells. Here we show that retinoic acid also triggers gr...

journal_title：Nature medicine

authors： Nasr R,Guillemin MC,Ferhi O,Soilihi H,Peres L,Berthier C,Rousselot P,Robledo-Sarmiento M,Lallemand-Breitenbach V,Gourmel B,Vitoux D,Pandolfi PP,Rochette-Egly C,Zhu J,de Thé H

更新日期：2008-12-01 00:00:00

abstract：:The major known genetic risk factors in multiple sclerosis reside in the major histocompatibility complex (MHC) region. Although there is strong evidence implicating MHC class II alleles and CD4(+) T cells in multiple sclerosis pathogenesis, possible contributions from MHC class I genes and CD8(+) T cells are controve...

journal_title：Nature medicine

authors： Friese MA,Jakobsen KB,Friis L,Etzensperger R,Craner MJ,McMahon RM,Jensen LT,Huygelen V,Jones EY,Bell JI,Fugger L

更新日期：2008-11-01 00:00:00

abstract：:Two big challenges of transplantation biology are controlling the reaction of the graft to the host after hematopoietic stem cell transplantation and preventing rejection of donor organs by the host. Raewyn Broady and Megan K. Levings discuss the first challenge, examining studies suggesting that statins might be help...

journal_title：Nature medicine

authors： Broady R,Levings MK

更新日期：2008-11-01 00:00:00

abstract：:Because of their abundance, resistance to proteolysis, rapid aggregation and neurotoxicity, N-terminally truncated and, in particular, pyroglutamate (pE)-modified Abeta peptides have been suggested as being important in the initiation of pathological cascades resulting in the development of Alzheimer's disease. We fou...

journal_title：Nature medicine

authors： Schilling S,Zeitschel U,Hoffmann T,Heiser U,Francke M,Kehlen A,Holzer M,Hutter-Paier B,Prokesch M,Windisch M,Jagla W,Schlenzig D,Lindner C,Rudolph T,Reuter G,Cynis H,Montag D,Demuth HU,Rossner S

更新日期：2008-10-01 00:00:00

abstract：:Rapid and accurate measurement of biomarkers in tissue and fluid samples is a major challenge in medicine. Here we report the development of a new, miniaturized diagnostic magnetic resonance (DMR) system for multiplexed, quantitative and rapid analysis. By using magnetic particles as a proximity sensor to amplify mole...

journal_title：Nature medicine

authors： Lee H,Sun E,Ham D,Weissleder R

更新日期：2008-08-01 00:00:00

abstract：:Although prognostic gene expression signatures for survival in early-stage lung cancer have been proposed, for clinical application, it is critical to establish their performance across different subject populations and in different laboratories. Here we report a large, training-testing, multi-site, blinded validation...

journal_title：Nature medicine

authors： Director's Challenge Consortium for the Molecular Classification of Lung Adenocarcinoma.,Shedden K,Taylor JM,Enkemann SA,Tsao MS,Yeatman TJ,Gerald WL,Eschrich S,Jurisica I,Giordano TJ,Misek DE,Chang AC,Zhu CQ,Strumpf D,Hanash

更新日期：2008-08-01 00:00:00

abstract：:Reactive oxygen species (ROS) induce chemokines responsible for the recruitment of inflammatory cells to sites of injury or infection. Here we show that the plasma membrane Ca(2+)-permeable channel TRPM2 controls ROS-induced chemokine production in monocytes. In human U937 monocytes, hydrogen peroxide (H(2)O(2)) evoke...

journal_title：Nature medicine

authors： Yamamoto S,Shimizu S,Kiyonaka S,Takahashi N,Wajima T,Hara Y,Negoro T,Hiroi T,Kiuchi Y,Okada T,Kaneko S,Lange I,Fleig A,Penner R,Nishi M,Takeshima H,Mori Y

更新日期：2008-07-01 00:00:00

abstract：:Obesity and metabolic syndrome are increasingly recognized as major risk factors for cardiovascular disease. Herein we show that Krüppel-like transcription factor 5 (KLF5) is a crucial regulator of energy metabolism. Klf5(+/-) mice were resistant to high fat-induced obesity, hypercholesterolemia and glucose intoleranc...

journal_title：Nature medicine

authors： Oishi Y,Manabe I,Tobe K,Ohsugi M,Kubota T,Fujiu K,Maemura K,Kubota N,Kadowaki T,Nagai R

更新日期：2008-06-01 00:00:00

abstract：:Much effort has been devoted to the design of vaccines that induce adaptive cellular immunity, in particular CD8+ T cells, which have a central role in the host response to viral infections and cancers. To date, however, the development of effective T cell vaccines remains elusive. This is due, in part, to the lack of...

journal_title：Nature medicine

authors： Appay V,Douek DC,Price DA

更新日期：2008-06-01 00:00:00

abstract：:Beta-adrenergic receptor (betaAR) blockade is a standard therapy for cardiac failure and ischemia. G protein-coupled receptor kinases (GRKs) desensitize betaARs, suggesting that genetic GRK variants might modify outcomes in these syndromes. Re-sequencing of GRK2 and GRK5 revealed a nonsynonymous polymorphism of GRK5, ...

journal_title：Nature medicine

authors： Liggett SB,Cresci S,Kelly RJ,Syed FM,Matkovich SJ,Hahn HS,Diwan A,Martini JS,Sparks L,Parekh RR,Spertus JA,Koch WJ,Kardia SL,Dorn GW 2nd

更新日期：2008-05-01 00:00:00

abstract：:The penumbra is an area of brain tissue that is damaged but not yet dead after focal ischemia. The existence of a penumbra implies that therapeutic salvage is theoretically possible after stroke. The first decade of penumbral science investigated the ischemic regulation of electrophysiology, cerebral blood flow and me...

journal_title：Nature medicine

authors： Lo EH

更新日期：2008-05-01 00:00:00

abstract：:Noninvasive imaging at the molecular level is an emerging field in biomedical research. This paper introduces a new technology synergizing two leading imaging methodologies: positron emission tomography (PET) and magnetic resonance imaging (MRI). Although the value of PET lies in its high-sensitivity tracking of bioma...

journal_title：Nature medicine

authors： Judenhofer MS,Wehrl HF,Newport DF,Catana C,Siegel SB,Becker M,Thielscher A,Kneilling M,Lichy MP,Eichner M,Klingel K,Reischl G,Widmaier S,Röcken M,Nutt RE,Machulla HJ,Uludag K,Cherry SR,Claussen CD,Pichler BJ

更新日期：2008-04-01 00:00:00

abstract：:Treatment for schistosomiasis, which is responsible for more than 280,000 deaths annually, depends almost exclusively on praziquantel. Millions of people are treated annually with praziquantel, and drug-resistant parasites thus are likely to evolve. Phosphinic amides and oxadiazole 2-oxides, identified from a quantita...

journal_title：Nature medicine

authors： Sayed AA,Simeonov A,Thomas CJ,Inglese J,Austin CP,Williams DL

更新日期：2008-04-01 00:00:00

abstract：:Emerging evidence supports the concept that T helper type 17 (T(H)17) cells, in addition to mediating autoimmunity, have key roles in mucosal immunity against extracellular pathogens. Interleukin-22 (IL-22) and IL-17A are both effector cytokines produced by the T(H)17 lineage, and both were crucial for maintaining loc...

journal_title：Nature medicine

authors： Aujla SJ,Chan YR,Zheng M,Fei M,Askew DJ,Pociask DA,Reinhart TA,McAllister F,Edeal J,Gaus K,Husain S,Kreindler JL,Dubin PJ,Pilewski JM,Myerburg MM,Mason CA,Iwakura Y,Kolls JK

更新日期：2008-03-01 00:00:00

abstract：:Regulatory T cells (T(reg) cells) suppress autoreactive immune responses and limit the efficacy of tumor vaccines; however, it remains a challenge to selectively eliminate or inhibit T(reg) cells. In this study, the zinc-finger A20, a negative regulator of the Toll-like receptor and tumor necrosis factor receptor sign...

journal_title：Nature medicine

authors： Song XT,Evel-Kabler K,Shen L,Rollins L,Huang XF,Chen SY

更新日期：2008-03-01 00:00:00

abstract：:Insulin receptor substrate (IRS)-1 and IRS-2 have dominant roles in the action of insulin, but other substrates of the insulin receptor kinase, such as Gab1, c-Cbl, SH2-B and APS, are also of physiological relevance. Although the protein downstream of tyrosine kinases-1 (Dok1) is known to function as a multisite adapt...

journal_title：Nature medicine

authors： Hosooka T,Noguchi T,Kotani K,Nakamura T,Sakaue H,Inoue H,Ogawa W,Tobimatsu K,Takazawa K,Sakai M,Matsuki Y,Hiramatsu R,Yasuda T,Lazar MA,Yamanashi Y,Kasuga M

更新日期：2008-02-01 00:00:00

abstract：:Beta-catenin is a central molecule in the Wnt pathway. Expression of a stable form of beta-catenin on CD4+CD25+ regulatory T (T(reg)) cells resulted in a marked enhancement of survival of these cells in vitro. Furthermore, stable beta-catenin-expressing CD4+CD25+ T(reg) cells outcompeted control T(reg) cells in vivo, ...

journal_title：Nature medicine

authors： Ding Y,Shen S,Lino AC,Curotto de Lafaille MA,Lafaille JJ

更新日期：2008-02-01 00:00:00

abstract：:Deep brain stimulation (DBS) is a widely used neurosurgical approach to treating tremor and other movement disorders. In addition, the use of DBS in a number of psychiatric diseases, including obsessive-compulsive disorders and depression, is currently being tested. Despite the rapid increase in the number of individu...

journal_title：Nature medicine

authors： Bekar L,Libionka W,Tian GF,Xu Q,Torres A,Wang X,Lovatt D,Williams E,Takano T,Schnermann J,Bakos R,Nedergaard M

更新日期：2008-01-01 00:00:00

abstract：:Surgery or radiation therapy of metastatic cancer often damages lymph nodes, leading to secondary lymphedema. Here we show, using a newly established mouse model, that collecting lymphatic vessels can be regenerated and fused to lymph node transplants after lymph node removal. Treatment of lymph node-excised mice with...

journal_title：Nature medicine

authors： Tammela T,Saaristo A,Holopainen T,Lyytikkä J,Kotronen A,Pitkonen M,Abo-Ramadan U,Ylä-Herttuala S,Petrova TV,Alitalo K

更新日期：2007-12-01 00:00:00

abstract：:Autosomal dominant polycystic kidney disease is an important cause of end-stage renal disease, for which there is no proven therapy. Mutations in PKD1 (the gene encoding polycystin-1) are the principal cause of this disease. The disease begins in utero and is slowly progressive, but it is not known whether cystogenesi...

journal_title：Nature medicine

authors： Piontek K,Menezes LF,Garcia-Gonzalez MA,Huso DL,Germino GG

更新日期：2007-12-01 00:00:00

abstract：:Sepsis, a leading cause of death worldwide, involves proinflammatory responses and inefficient bacterial clearance. Phagocytic cells play a crucial part in the prevention of sepsis by clearing bacteria through host innate receptors. Here we show that the FcRgamma adaptor, an immunoreceptor tyrosine-based activation mo...

journal_title：Nature medicine

authors： Pinheiro da Silva F,Aloulou M,Skurnik D,Benhamou M,Andremont A,Velasco IT,Chiamolera M,Verbeek JS,Launay P,Monteiro RC

更新日期：2007-11-01 00:00:00

abstract：:Hepatic injury is associated with a defective intestinal barrier and increased hepatic exposure to bacterial products. Here we report that the intestinal bacterial microflora and a functional Toll-like receptor 4 (TLR4), but not TLR2, are required for hepatic fibrogenesis. Using Tlr4-chimeric mice and in vivo lipopoly...

journal_title：Nature medicine

authors： Seki E,De Minicis S,Osterreicher CH,Kluwe J,Osawa Y,Brenner DA,Schwabe RF

更新日期：2007-11-01 00:00:00

abstract：:Histone/protein deacetylases (HDACs) regulate chromatin remodeling and gene expression as well as the functions of more than 50 transcription factors and nonhistone proteins. We found that administration of an HDAC inhibitor (HDACi) in vivo increased Foxp3 gene expression, as well as the production and suppressive fun...

journal_title：Nature medicine

authors： Tao R,de Zoeten EF,Ozkaynak E,Chen C,Wang L,Porrett PM,Li B,Turka LA,Olson EN,Greene MI,Wells AD,Hancock WW

更新日期：2007-11-01 00:00:00

abstract：:The cardioprotective effects of estrogen are mediated by receptors expressed in vascular cells. Here we show that 27-hydroxycholesterol (27HC), an abundant cholesterol metabolite that is elevated with hypercholesterolemia and found in atherosclerotic lesions, is a competitive antagonist of estrogen receptor action in ...

journal_title：Nature medicine

authors： Umetani M,Domoto H,Gormley AK,Yuhanna IS,Cummins CL,Javitt NB,Korach KS,Shaul PW,Mangelsdorf DJ

更新日期：2007-10-01 00:00:00

abstract：:Sepsis remains a global clinical problem. By using the mouse cecal ligation and puncture model of sepsis, here we identify an important aspect of mast cell (MC)-dependent, innate immune defenses against Gram-negative bacteria by demonstrating that MC protease activity is regulated by interleukin-15 (IL-15). Mouse MCs ...

journal_title：Nature medicine

authors： Orinska Z,Maurer M,Mirghomizadeh F,Bulanova E,Metz M,Nashkevich N,Schiemann F,Schulmistrat J,Budagian V,Giron-Michel J,Brandt E,Paus R,Bulfone-Paus S

更新日期：2007-08-01 00:00:00

abstract：:Treatment with glatiramer acetate (GA, copolymer-1, Copaxone), a drug approved for multiple sclerosis (MS), in a mouse model promoted development of anti-inflammatory type II monocytes, characterized by increased secretion of interleukin (IL)-10 and transforming growth factor (TGF)-beta, and decreased production of IL...

journal_title：Nature medicine

authors： Weber MS,Prod'homme T,Youssef S,Dunn SE,Rundle CD,Lee L,Patarroyo JC,Stüve O,Sobel RA,Steinman L,Zamvil SS

更新日期：2007-08-01 00:00:00

abstract：:Gamma-aminobutyric acid (GABA) is an important neurotransmitter that, through the subtype A GABA receptor (GABAAR), induces inhibition in the adult brain. Here we show that an excitatory, rather than inhibitory, GABAergic system exists in airway epithelial cells. Both GABAARs and the GABA synthetic enzyme glutamic aci...

journal_title：Nature medicine

authors： Xiang YY,Wang S,Liu M,Hirota JA,Li J,Ju W,Fan Y,Kelly MM,Ye B,Orser B,O'Byrne PM,Inman MD,Yang X,Lu WY

更新日期：2007-07-01 00:00:00

abstract：:The use of genetically manipulated mouse models, gene and protein discovery and the cataloguing of genetic mutations have each allowed us to obtain new insights into skeletal morphogenesis and remodeling. These techniques have made it possible to identify molecules that are obligatory for specific cellular functions, ...

journal_title：Nature medicine

authors： Zaidi M

更新日期：2007-07-01 00:00:00

abstract：:T-helper type 17 cells (T(H)17) are implicated in rodent models of immune-mediated diseases. Here we report their involvement in human uveitis and scleritis, and validate our findings in experimental autoimmune uveoretinitis (EAU), a model of uveitis. T(H)17 cells were present in human peripheral blood mononuclear cel...

journal_title：Nature medicine

authors： Amadi-Obi A,Yu CR,Liu X,Mahdi RM,Clarke GL,Nussenblatt RB,Gery I,Lee YS,Egwuagu CE

更新日期：2007-06-01 00:00:00

abstract：:Misfolding of Cu/Zn-superoxide dismutase (SOD1) is emerging as a mechanism underlying motor neuron degeneration in individuals with amyotrophic lateral sclerosis (ALS) who carry a mutant SOD1 gene (SOD1 ALS). Here we describe a structure-guided approach to developing an antibody that specifically recognizes monomer-mi...

journal_title：Nature medicine

authors： Rakhit R,Robertson J,Vande Velde C,Horne P,Ruth DM,Griffin J,Cleveland DW,Cashman NR,Chakrabartty A

更新日期：2007-06-01 00:00:00

abstract：:Osteopontin (Opn) is important for T helper type 1 (T(H)1) immunity and autoimmunity. However, the role of this cytokine in T(H)2-mediated allergic disease as well as its effects on primary versus secondary antigenic encounters remain unclear. Here we demonstrate that OPN is expressed in the lungs of asthmatic individ...

journal_title：Nature medicine

authors： Xanthou G,Alissafi T,Semitekolou M,Simoes DC,Economidou E,Gaga M,Lambrecht BN,Lloyd CM,Panoutsakopoulou V

更新日期：2007-05-01 00:00:00

abstract：:Sympathetic innervation is critical for effective cardiac function. However, the developmental and regulatory mechanisms determining the density and patterning of cardiac sympathetic innervation remain unclear, as does the role of this innervation in arrhythmogenesis. Here we show that a neural chemorepellent, Sema3a,...

journal_title：Nature medicine

authors： Ieda M,Kanazawa H,Kimura K,Hattori F,Ieda Y,Taniguchi M,Lee JK,Matsumura K,Tomita Y,Miyoshi S,Shimoda K,Makino S,Sano M,Kodama I,Ogawa S,Fukuda K

更新日期：2007-05-01 00:00:00

abstract：:We formulate a two-phase paradigm of autoimmunity associated with systemic lupus erythematosus, the archetypal autoimmune disease. The initial Toll-like receptor (TLR)-independent phase is mediated by dendritic cell uptake of apoptotic cell debris and associated nucleic acids, whereas the subsequent TLR-dependent phas...

journal_title：Nature medicine

authors： Baccala R,Hoebe K,Kono DH,Beutler B,Theofilopoulos AN

更新日期：2007-05-01 00:00:00

abstract：:Autophagy, an evolutionarily conserved process for the bulk degradation of cytoplasmic components, serves as a cell survival mechanism in starving cells. Although altered autophagy has been observed in various heart diseases, including cardiac hypertrophy and heart failure, it remains unclear whether autophagy plays a...

journal_title：Nature medicine

authors： Nakai A,Yamaguchi O,Takeda T,Higuchi Y,Hikoso S,Taniike M,Omiya S,Mizote I,Matsumura Y,Asahi M,Nishida K,Hori M,Mizushima N,Otsu K

更新日期：2007-05-01 00:00:00

abstract：:Hereditary hemochromatosis and transfusional iron overload are frequent clinical conditions associated with progressive iron accumulation in parenchymal tissues, leading to eventual organ failure. We have discovered a new mechanism to reverse iron overload-pharmacological modulation of the divalent metal transporter-1...

journal_title：Nature medicine

authors： Ludwiczek S,Theurl I,Muckenthaler MU,Jakab M,Mair SM,Theurl M,Kiss J,Paulmichl M,Hentze MW,Ritter M,Weiss G

更新日期：2007-04-01 00:00:00

abstract：:Lung cancer is the leading cause of death from cancer in the US and the world. The high mortality rate (80-85% within 5 years) results, in part, from a lack of effective tools to diagnose the disease at an early stage. Given that cigarette smoke creates a field of injury throughout the airway, we sought to determine i...

journal_title：Nature medicine

authors： Spira A,Beane JE,Shah V,Steiling K,Liu G,Schembri F,Gilman S,Dumas YM,Calner P,Sebastiani P,Sridhar S,Beamis J,Lamb C,Anderson T,Gerry N,Keane J,Lenburg ME,Brody JS

更新日期：2007-03-01 00:00:00

abstract：:Increased production of very low-density lipoprotein (VLDL) is a critical feature of the metabolic syndrome. Here we report that a selective increase in brain glucose lowered circulating triglycerides (TG) through the inhibition of TG-VLDL secretion by the liver. We found that the effect of glucose required its conver...

journal_title：Nature medicine

authors： Lam TK,Gutierrez-Juarez R,Pocai A,Bhanot S,Tso P,Schwartz GJ,Rossetti L

更新日期：2007-02-01 00:00:00

abstract：:T-cell acute lymphoblastic leukemia (T-ALL), unlike other ALL types, is only infrequently associated with chromosomal aberrations, but it was recently shown that most individuals with T-ALL carry activating mutations in the NOTCH1 gene. However, the signaling pathways and target genes responsible for Notch1-induced ne...

journal_title：Nature medicine

authors： Vilimas T,Mascarenhas J,Palomero T,Mandal M,Buonamici S,Meng F,Thompson B,Spaulding C,Macaroun S,Alegre ML,Kee BL,Ferrando A,Miele L,Aifantis I

更新日期：2007-01-01 00:00:00

abstract：:Matrix-producing osteoblasts and bone-resorbing osteoclasts maintain bone homeostasis. Osteoclasts are multinucleated, giant cells of hematopoietic origin formed by the fusion of mononuclear pre-osteoclasts derived from myeloid cells. Fusion-mediated giant cell formation is critical for osteoclast maturation; without ...

journal_title：Nature medicine

authors： Lee SH,Rho J,Jeong D,Sul JY,Kim T,Kim N,Kang JS,Miyamoto T,Suda T,Lee SK,Pignolo RJ,Koczon-Jaremko B,Lorenzo J,Choi Y

更新日期：2006-12-01 00:00:00

abstract：:The role of nitric oxide (NO) in the genesis of cerebral malaria is controversial. Most investigators propose that the unfortunate consequence of the high concentrations of NO produced to kill the parasite is the development of cerebral malaria. Here we have tested this high NO bioavailability hypothesis in the settin...

journal_title：Nature medicine

authors： Gramaglia I,Sobolewski P,Meays D,Contreras R,Nolan JP,Frangos JA,Intaglietta M,van der Heyde HC

更新日期：2006-12-01 00:00:00