abstract：:Pulmonary hypertension (PH) is characterized by increased proliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs). Forkhead box O (FoxO) transcription factors are key regulators of cellular proliferation. Here we show that in pulmonary vessels and PASMCs of human and experimental PH lun...

journal_title：Nature medicine

authors： Savai R,Al-Tamari HM,Sedding D,Kojonazarov B,Muecke C,Teske R,Capecchi MR,Weissmann N,Grimminger F,Seeger W,Schermuly RT,Pullamsetti SS

更新日期：2014-11-01 00:00:00

abstract：:Neurofibrillary tangles (NFTs), composed of truncated and hyperphosphorylated tau, are a common feature of numerous aging-related neurodegenerative diseases, including Alzheimer's disease (AD). However, the molecular mechanisms mediating tau truncation and aggregation during aging remain elusive. Here we show that asp...

journal_title：Nature medicine

authors： Zhang Z,Song M,Liu X,Kang SS,Kwon IS,Duong DM,Seyfried NT,Hu WT,Liu Z,Wang JZ,Cheng L,Sun YE,Yu SP,Levey AI,Ye K

更新日期：2014-11-01 00:00:00

abstract：:Efforts to identify and annotate cancer driver genetic lesions have been focused primarily on the analysis of protein-coding genes; however, most genetic abnormalities found in human cancer are located in intergenic regions. Here we identify a new long range-acting MYC enhancer controlled by NOTCH1 that is targeted by...

journal_title：Nature medicine

authors： Herranz D,Ambesi-Impiombato A,Palomero T,Schnell SA,Belver L,Wendorff AA,Xu L,Castillo-Martin M,Llobet-Navás D,Cordon-Cardo C,Clappier E,Soulier J,Ferrando AA

更新日期：2014-10-01 00:00:00

abstract：:Technologies are needed to map and image biological barriers in vivo that limit solid tumor delivery and, ultimately, the effectiveness of imaging and therapeutic agents. Here we integrate proteomic and imaging analyses of caveolae at the blood-tumor interface to discover an active transendothelial portal to infiltrat...

journal_title：Nature medicine

authors： Oh P,Testa JE,Borgstrom P,Witkiewicz H,Li Y,Schnitzer JE

更新日期：2014-09-01 00:00:00

abstract：:Restriction factors are host cell proteins that inhibit retroviral infection. A new study using mutants of human HIV-1 restriction factor SAMHD1 suggests that it inhibits infection through degradation of viral RNA rather than through its dNTPase activity as previously suggested. ...

journal_title：Nature medicine

authors： Yang Z,Greene WC

更新日期：2014-08-01 00:00:00

abstract：:The skin protects mammals from insults, infection and dehydration and enables thermoregulation and sensory perception. Various skin-resident cells carry out these diverse functions. Constant turnover of cells and healing upon injury necessitate multiple reservoirs of stem cells. Thus, the skin provides a model for stu...

journal_title：Nature medicine

authors： Hsu YC,Li L,Fuchs E

更新日期：2014-08-01 00:00:00

abstract：:Hedgehog signaling drives oncogenesis in several cancers, and strategies targeting this pathway have been developed, most notably through inhibition of Smoothened (SMO). However, resistance to Smoothened inhibitors occurs by genetic changes of Smoothened or other downstream Hedgehog components. Here we overcome these ...

journal_title：Nature medicine

authors： Tang Y,Gholamin S,Schubert S,Willardson MI,Lee A,Bandopadhayay P,Bergthold G,Masoud S,Nguyen B,Vue N,Balansay B,Yu F,Oh S,Woo P,Chen S,Ponnuswami A,Monje M,Atwood SX,Whitson RJ,Mitra S,Cheshier SH,Qi J,Beroukh

更新日期：2014-07-01 00:00:00

abstract：:The N-terminal fragment of prolactin (16K PRL) inhibits tumor growth by impairing angiogenesis, but the underlying mechanisms are unknown. Here, we found that 16K PRL binds the fibrinolytic inhibitor plasminogen activator inhibitor-1 (PAI-1), which is known to contextually promote tumor angiogenesis and growth. Loss o...

journal_title：Nature medicine

authors： Bajou K,Herkenne S,Thijssen VL,D'Amico S,Nguyen NQ,Bouché A,Tabruyn S,Srahna M,Carabin JY,Nivelles O,Paques C,Cornelissen I,Lion M,Noel A,Gils A,Vinckier S,Declerck PJ,Griffioen AW,Dewerchin M,Martial JA,Carmeliet

更新日期：2014-07-01 00:00:00

abstract：:Immune evasion is an emerging hallmark of cancer progression. However, functional studies to understand the role of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment are limited by the lack of available specific cell surface markers. We adapted a competitive peptide phage display platform to ident...

journal_title：Nature medicine

authors： Qin H,Lerman B,Sakamaki I,Wei G,Cha SC,Rao SS,Qian J,Hailemichael Y,Nurieva R,Dwyer KC,Roth J,Yi Q,Overwijk WW,Kwak LW

更新日期：2014-06-01 00:00:00

abstract：:We previously demonstrated that low biosynthesis of ω-3 fatty acid-derived proresolution mediators, termed protectins, is associated with an impaired global resolution capacity, inflammation and insulin resistance in obese high-fat diet-fed mice. These findings prompted a more direct study of the therapeutic potential...

journal_title：Nature medicine

authors： White PJ,St-Pierre P,Charbonneau A,Mitchell PL,St-Amand E,Marcotte B,Marette A

更新日期：2014-06-01 00:00:00

abstract：:Liver disease is one of the leading causes of death worldwide. Patients with cirrhosis display an increased predisposition to and mortality from infection due to multimodal defects in the innate immune system; however, the causative mechanism has remained elusive. We present evidence that the cyclooxygenase (COX)-deri...

journal_title：Nature medicine

authors： O'Brien AJ,Fullerton JN,Massey KA,Auld G,Sewell G,James S,Newson J,Karra E,Winstanley A,Alazawi W,Garcia-Martinez R,Cordoba J,Nicolaou A,Gilroy DW

更新日期：2014-05-01 00:00:00

abstract：:Huntington's disease (HD) is a fatal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion leading to an elongated polyglutamine stretch in huntingtin. Mutant huntingtin (mHTT) is ubiquitously expressed in all cells but elicits selective cortical and striatal neurodegeneration in HD. The mec...

journal_title：Nature medicine

authors： Wang N,Gray M,Lu XH,Cantle JP,Holley SM,Greiner E,Gu X,Shirasaki D,Cepeda C,Li Y,Dong H,Levine MS,Yang XW

更新日期：2014-05-01 00:00:00

abstract：:Despite the central role of the liver in the regulation of glucose and lipid metabolism, there are currently no methods to directly assess hepatic oxidative metabolism in humans in vivo. By using a new (13)C-labeling strategy in combination with (13)C magnetic resonance spectroscopy, we show that rates of mitochondria...

journal_title：Nature medicine

authors： Befroy DE,Perry RJ,Jain N,Dufour S,Cline GW,Trimmer JK,Brosnan J,Rothman DL,Petersen KF,Shulman GI

更新日期：2014-01-01 00:00:00

abstract：:The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) is of global concern: the virus has caused severe respiratory illness, with 111 confirmed cases and 52 deaths at the time of this article's publication. Therapeutic interventions have not been evaluated in vivo; thus, patient management relies ex...

journal_title：Nature medicine

authors： Falzarano D,de Wit E,Rasmussen AL,Feldmann F,Okumura A,Scott DP,Brining D,Bushmaker T,Martellaro C,Baseler L,Benecke AG,Katze MG,Munster VJ,Feldmann H

更新日期：2013-10-01 00:00:00

abstract：:A signaling cascade is activated in podocytes to induce survival and cope with stress during advanced glomerular disease, a new study shows. The findings may also explain why the immunosuppressor sirolimus, an inhibitor of this pathway, can cause proteinuria in a subset of patients with chronic kidney disease (pages 1...

journal_title：Nature medicine

authors： Reiser J

更新日期：2013-10-01 00:00:00

abstract：:In chronic kidney disease (CKD), loss of functional nephrons results in metabolic and mechanical stress in the remaining ones, resulting in further nephron loss. Here we show that Akt2 activation has an essential role in podocyte protection after nephron reduction. Glomerulosclerosis and albuminuria were substantially...

journal_title：Nature medicine

authors： Canaud G,Bienaimé F,Viau A,Treins C,Baron W,Nguyen C,Burtin M,Berissi S,Giannakakis K,Muda AO,Zschiedrich S,Huber TB,Friedlander G,Legendre C,Pontoglio M,Pende M,Terzi F

更新日期：2013-10-01 00:00:00

abstract：:It begins as a slowly expanding spot of light or similar visual disturbance, often accompanied by phantom noises and other sensory distortions. People who experience such 'auras' know all too well that these early warning signs will culminate in a head-splitting migraine, yet scientists have little idea what causes th...

journal_title：Nature medicine

authors： Dolgin E

更新日期：2013-09-01 00:00:00

abstract：:Tumors have a greater reliance on anaerobic glycolysis for energy production than normal tissues. We developed a noninvasive method for imaging glucose uptake in vivo that is based on magnetic resonance imaging and allows the uptake of unlabeled glucose to be measured through the chemical exchange of protons between h...

journal_title：Nature medicine

authors： Walker-Samuel S,Ramasawmy R,Torrealdea F,Rega M,Rajkumar V,Johnson SP,Richardson S,Gonçalves M,Parkes HG,Arstad E,Thomas DL,Pedley RB,Lythgoe MF,Golay X

更新日期：2013-08-01 00:00:00

abstract：:Huntington's disease is caused by an expanded polyglutamine repeat in the huntingtin protein (HTT), but the pathophysiological sequence of events that trigger synaptic failure and neuronal loss are not fully understood. Alterations in N-methyl-D-aspartate (NMDA)-type glutamate receptors (NMDARs) have been implicated. ...

journal_title：Nature medicine

authors： Marco S,Giralt A,Petrovic MM,Pouladi MA,Martínez-Turrillas R,Martínez-Hernández J,Kaltenbach LS,Torres-Peraza J,Graham RK,Watanabe M,Luján R,Nakanishi N,Lipton SA,Lo DC,Hayden MR,Alberch J,Wesseling JF,Pérez-Otaño I

更新日期：2013-08-01 00:00:00

abstract：:Parasites of the Leishmania genus are the causative agents of leishmaniasis in humans, a disease that affects more than 12 million people worldwide. These parasites replicate intracellularly in macrophages, and the primary mechanisms underlying host resistance involve the production of nitric oxide (NO). In this study...

journal_title：Nature medicine

authors： Lima-Junior DS,Costa DL,Carregaro V,Cunha LD,Silva AL,Mineo TW,Gutierrez FR,Bellio M,Bortoluci KR,Flavell RA,Bozza MT,Silva JS,Zamboni DS

更新日期：2013-07-01 00:00:00

abstract：:The ability to patent human genes has been costly to researchers and patients, and has restricted competition in the biotech marketplace. The recent US Supreme Court decision making isolated human genes unpatentable will bring freedom of choice to the patient, and level the playing field for research and development. ...

journal_title：Nature medicine

authors：

更新日期：2013-07-01 00:00:00

abstract：:Oxidative damage from elevated production of reactive oxygen species (ROS) contributes to ischemia-reperfusion injury in myocardial infarction and stroke. The mechanism by which the increase in ROS occurs is not known, and it is unclear how this increase can be prevented. A wide variety of nitric oxide donors and S-ni...

journal_title：Nature medicine

authors： Chouchani ET,Methner C,Nadtochiy SM,Logan A,Pell VR,Ding S,James AM,Cochemé HM,Reinhold J,Lilley KS,Partridge L,Fearnley IM,Robinson AJ,Hartley RC,Smith RA,Krieg T,Brookes PS,Murphy MP

更新日期：2013-06-01 00:00:00

abstract：:Multiple sclerosis is an autoimmune disease of the central nervous system (CNS) that is initiated when self-reactive T cells enter the brain and become locally activated after encountering their specific nervous antigens. When and where the disease-relevant antigen encounters occur is unclear. Here we combined fluores...

journal_title：Nature medicine

authors： Lodygin D,Odoardi F,Schläger C,Körner H,Kitz A,Nosov M,van den Brandt J,Reichardt HM,Haberl M,Flügel A

更新日期：2013-06-01 00:00:00

abstract：:A new regulatory pathway established last year allows drugs with dramatic early clinical promise to be expedited to the market quicker than ever before. To date, most of these 'breakthrough' designations have gone to cancer agents, raising the prospect of faster access to the latest lifesaving therapies for the estima...

journal_title：Nature medicine

authors： Dolgin E

更新日期：2013-06-01 00:00:00

abstract：:Osteoarthritis is a highly prevalent and debilitating joint disorder. There is no effective medical therapy for the condition because of limited understanding of its pathogenesis. We show that transforming growth factor β1 (TGF-β1) is activated in subchondral bone in response to altered mechanical loading in an anteri...

journal_title：Nature medicine

authors： Zhen G,Wen C,Jia X,Li Y,Crane JL,Mears SC,Askin FB,Frassica FJ,Chang W,Yao J,Carrino JA,Cosgarea A,Artemov D,Chen Q,Zhao Z,Zhou X,Riley L,Sponseller P,Wan M,Lu WW,Cao X

更新日期：2013-06-01 00:00:00

abstract：:Colon cancer is a clinically diverse disease. This heterogeneity makes it difficult to determine which patients will benefit most from adjuvant therapy and impedes the development of new targeted agents. More insight into the biological diversity of colon cancers, especially in relation to clinical features, is theref...

journal_title：Nature medicine

authors： De Sousa E Melo F,Wang X,Jansen M,Fessler E,Trinh A,de Rooij LP,de Jong JH,de Boer OJ,van Leersum R,Bijlsma MF,Rodermond H,van der Heijden M,van Noesel CJ,Tuynman JB,Dekker E,Markowetz F,Medema JP,Vermeulen L

更新日期：2013-05-01 00:00:00

abstract：:Focal segmental glomerulosclerosis (FSGS) is a frequent and severe glomerular disease characterized by destabilization of podocyte foot processes. We report that transgenic expression of the microRNA miR-193a in mice rapidly induces FSGS with extensive podocyte foot process effacement. Mechanistically, miR-193a inhibi...

journal_title：Nature medicine

authors： Gebeshuber CA,Kornauth C,Dong L,Sierig R,Seibler J,Reiss M,Tauber S,Bilban M,Wang S,Kain R,Böhmig GA,Moeller MJ,Gröne HJ,Englert C,Martinez J,Kerjaschki D

更新日期：2013-04-01 00:00:00

abstract：:Hearing impairment is the most common sensory disorder, with congenital hearing impairment present in approximately 1 in 1,000 newborns. Hereditary deafness is often mediated by the improper development or degeneration of cochlear hair cells. Until now, it was not known whether such congenital failures could be mitiga...

journal_title：Nature medicine

authors： Lentz JJ,Jodelka FM,Hinrich AJ,McCaffrey KE,Farris HE,Spalitta MJ,Bazan NG,Duelli DM,Rigo F,Hastings ML

更新日期：2013-03-01 00:00:00

abstract：:Delayed T cell recovery and restricted T cell receptor (TCR) diversity after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are associated with increased risks of infection and cancer relapse. Technical challenges have limited faithful measurement of TCR diversity after allo-HSCT. Here we combined 5' r...

journal_title：Nature medicine

authors： van Heijst JW,Ceberio I,Lipuma LB,Samilo DW,Wasilewski GD,Gonzales AM,Nieves JL,van den Brink MR,Perales MA,Pamer EG

更新日期：2013-03-01 00:00:00

abstract：:The mechanisms that regulate hematopoietic stem cell (HSC) regeneration after myelosuppressive injury are not well understood. We identified epidermal growth factor (EGF) to be highly enriched in the bone marrow serum of mice bearing deletion of Bak and Bax in TIE2-expressing cells in Tie2Cre; Bak1(-/-); Bax(flox/-) m...

journal_title：Nature medicine

authors： Doan PL,Himburg HA,Helms K,Russell JL,Fixsen E,Quarmyne M,Harris JR,Deoliviera D,Sullivan JM,Chao NJ,Kirsch DG,Chute JP

更新日期：2013-03-01 00:00:00

abstract：:Hepatic insulin resistance is a driving force in the pathogenesis of type 2 diabetes mellitus (T2DM) and is tightly coupled with excessive storage of fat and the ensuing inflammation within the liver. There is compelling evidence that activation of the transcription factor nuclear factor-κB (NF-κB) and downstream infl...

journal_title：Nature medicine

authors： Kiechl S,Wittmann J,Giaccari A,Knoflach M,Willeit P,Bozec A,Moschen AR,Muscogiuri G,Sorice GP,Kireva T,Summerer M,Wirtz S,Luther J,Mielenz D,Billmeier U,Egger G,Mayr A,Oberhollenzer F,Kronenberg F,Orthofer M,Penni

更新日期：2013-03-01 00:00:00

abstract：:Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are key regulators of the apoptotic process. This family comprises proapoptotic and prosurvival proteins, and shifting the balance toward the latter is an established mechanism whereby cancer cells evade apoptosis. The therapeutic potential of directly inhibiting pr...

journal_title：Nature medicine

authors： Souers AJ,Leverson JD,Boghaert ER,Ackler SL,Catron ND,Chen J,Dayton BD,Ding H,Enschede SH,Fairbrother WJ,Huang DC,Hymowitz SG,Jin S,Khaw SL,Kovar PJ,Lam LT,Lee J,Maecker HL,Marsh KC,Mason KD,Mitten MJ,Nimmer PM

更新日期：2013-02-01 00:00:00

abstract：:We report the development of a new combinatorial approach that allows for peptide-mediated selective tissue targeting of nuclear hormone pharmacology while eliminating adverse effects in other tissues. Specifically, we report the development of a glucagon-like peptide-1 (GLP-1)-estrogen conjugate that has superior sex...

journal_title：Nature medicine

authors： Finan B,Yang B,Ottaway N,Stemmer K,Müller TD,Yi CX,Habegger K,Schriever SC,García-Cáceres C,Kabra DG,Hembree J,Holland J,Raver C,Seeley RJ,Hans W,Irmler M,Beckers J,de Angelis MH,Tiano JP,Mauvais-Jarvis F,Perez-Ti

更新日期：2012-12-01 00:00:00

abstract：:A new study provides mechanistic insights into how live attenuated simian immunodeficiency virus (SIV) vaccines (LAVs) can protect monkeys from infection with pathogenic SIV. The authors show that replicating LAVs stimulate a protective immune response from a safe haven in the germinal centers of lymph nodes (pages 16...

journal_title：Nature medicine

authors： Robinson HL,Amara RR

更新日期：2012-11-01 00:00:00

abstract：:The ability of the human immune system to respond to vaccination declines with age. We identified an age-associated defect in T cell receptor (TCR)-induced extracellular signal-regulated kinase (ERK) phosphorylation in naive CD4(+) T cells, whereas other signals, such as ζ chain-associated protein kinase 70 (ZAP70) an...

journal_title：Nature medicine

authors： Li G,Yu M,Lee WW,Tsang M,Krishnan E,Weyand CM,Goronzy JJ

更新日期：2012-10-01 00:00:00

abstract：:Neutrophil extracellular traps (NETs) are released as neutrophils die in vitro in a process requiring hours, leaving a temporal gap that invasive microbes may exploit. Neutrophils capable of migration and phagocytosis while undergoing NETosis have not been documented. During Gram-positive skin infections, we directly ...

journal_title：Nature medicine

authors： Yipp BG,Petri B,Salina D,Jenne CN,Scott BN,Zbytnuik LD,Pittman K,Asaduzzaman M,Wu K,Meijndert HC,Malawista SE,de Boisfleury Chevance A,Zhang K,Conly J,Kubes P

更新日期：2012-09-01 00:00:00

abstract：:Temporal lobe epilepsy (TLE) is accompanied by an abnormal location of granule cells in the dentate gyrus. Using a rat model of complex febrile seizures, which are thought to be a precipitating insult of TLE later in life, we report that aberrant migration of neonatal-generated granule cells results in granule cell ec...

journal_title：Nature medicine

authors： Koyama R,Tao K,Sasaki T,Ichikawa J,Miyamoto D,Muramatsu R,Matsuki N,Ikegaya Y

更新日期：2012-08-01 00:00:00

abstract：:Although the treatment of acute myeloid leukemia (AML) has improved substantially in the past three decades, more than half of all patients develop disease that is refractory to intensive chemotherapy. Functional genomics approaches offer a means to discover specific molecules mediating the aberrant growth and surviva...

journal_title：Nature medicine

authors： Kentsis A,Reed C,Rice KL,Sanda T,Rodig SJ,Tholouli E,Christie A,Valk PJ,Delwel R,Ngo V,Kutok JL,Dahlberg SE,Moreau LA,Byers RJ,Christensen JG,Vande Woude G,Licht JD,Kung AL,Staudt LM,Look AT

更新日期：2012-07-01 00:00:00

abstract：:Post-ischemic inflammation is an essential step in the progression of brain ischemia-reperfusion injury. However, the mechanism that activates infiltrating macrophages in the ischemic brain remains to be clarified. Here we demonstrate that peroxiredoxin (Prx) family proteins released extracellularly from necrotic brai...

journal_title：Nature medicine

authors： Shichita T,Hasegawa E,Kimura A,Morita R,Sakaguchi R,Takada I,Sekiya T,Ooboshi H,Kitazono T,Yanagawa T,Ishii T,Takahashi H,Mori S,Nishibori M,Kuroda K,Akira S,Miyake K,Yoshimura A

更新日期：2012-06-01 00:00:00

abstract：:Alternative splicing ensures the expression of functionally diverse proteins from individual genes; however, aberrant mRNA splicing is associated with various conditions, including heart disease. A recent study provides new mechanistic insights into heart failure by showing that a human cardiomyopathy-linked mutation ...

journal_title：Nature medicine

authors： Linke WA,Bücker S

更新日期：2012-05-04 00:00:00