Up against the wall.

abstract：:It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene1. The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches2-5. For patients in whom WES is uninformative...

journal_title：Nature medicine

authors： Frésard L,Smail C,Ferraro NM,Teran NA,Li X,Smith KS,Bonner D,Kernohan KD,Marwaha S,Zappala Z,Balliu B,Davis JR,Liu B,Prybol CJ,Kohler JN,Zastrow DB,Reuter CM,Fisk DG,Grove ME,Davidson JM,Hartley T,Joshi R,Stro

更新日期：2019-06-01 00:00:00

abstract：:Recurrent medulloblastoma and ependymoma are universally lethal, with no approved targeted therapies and few candidates presently under clinical evaluation. Nearly all recurrent medulloblastomas and posterior fossa group A (PFA) ependymomas are located adjacent to and bathed by the cerebrospinal fluid, presenting an o...

journal_title：Nature medicine

authors： Donovan LK,Delaidelli A,Joseph SK,Bielamowicz K,Fousek K,Holgado BL,Manno A,Srikanthan D,Gad AZ,Van Ommeren R,Przelicki D,Richman C,Ramaswamy V,Daniels C,Pallota JG,Douglas T,Joynt ACM,Haapasalo J,Nor C,Vladoiu MC,

更新日期：2020-05-01 00:00:00

abstract：:The principles that govern the evolution of tumors exposed to targeted therapy are poorly understood. Here we modeled the selection and propagation of an amplification in the BRAF oncogene (BRAFamp) in patient-derived tumor xenografts (PDXs) that were treated with a direct inhibitor of the kinase ERK, either alone or ...

journal_title：Nature medicine

authors： Xue Y,Martelotto L,Baslan T,Vides A,Solomon M,Mai TT,Chaudhary N,Riely GJ,Li BT,Scott K,Cechhi F,Stierner U,Chadalavada K,de Stanchina E,Schwartz S,Hembrough T,Nanjangud G,Berger MF,Nilsson J,Lowe SW,Reis-Filho JS

更新日期：2017-08-01 00:00:00

abstract：:Use of wearable devices that monitor physical activity is projected to increase more than fivefold per half-decade1. We investigated how device-based physical activity energy expenditure (PAEE) and different intensity profiles were associated with all-cause mortality. We used a network harmonization approach to map do...

journal_title：Nature medicine

authors： Strain T,Wijndaele K,Dempsey PC,Sharp SJ,Pearce M,Jeon J,Lindsay T,Wareham N,Brage S

更新日期：2020-09-01 00:00:00

abstract：:The pathogenic bacterium Neisseria meningitidis is an important cause of septicemia and meningitis, especially in childhood. The establishment and maintenance of bacteremic infection is a pre-requisite for all the pathological sequelae of meningococcal infection. To further understand the genetic basis of this essenti...

journal_title：Nature medicine

authors： Sun YH,Bakshi S,Chalmers R,Tang CM

更新日期：2000-11-01 00:00:00

abstract：:We studied the effects of Lyn ablation on the survival of drug-resistant chronic myelogenous leukemia (CML) blast crisis cells using siRNA. Lyn siRNA reduced Lyn protein in both normal hematopoietic cells and BCR-ABL1-expressing (BCR-ABL1(+)) blasts by 80-95%. Within 48 h, siRNA-treated BCR-ABL1(+) blasts underwent ap...

journal_title：Nature medicine

authors： Ptasznik A,Nakata Y,Kalota A,Emerson SG,Gewirtz AM

更新日期：2004-11-01 00:00:00

abstract：:Peroxisome proliferator-activated receptor-delta (PPAR-delta; also known as PPAR-beta) is expressed at high levels in colon tumors, but its contribution to colon cancer is unclear. We examined the role of PPAR-delta in colon carcinogenesis using PPAR-delta-deficient (Ppard(-/-)) mice. In both the Min mutant and chemic...

journal_title：Nature medicine

authors： Harman FS,Nicol CJ,Marin HE,Ward JM,Gonzalez FJ,Peters JM

更新日期：2004-05-01 00:00:00

abstract：:A chimeric RNA/DNA oligonucleotide was constructed to induce a sequence mutation in the rat factor IX gene, resulting in prolonged coagulation. Oligonucleotides were targeted to hepatocytes in cell culture or in vivo by intravenous injection. Nucleotide conversion was both site-specific and dose-dependent. The mutated...

journal_title：Nature medicine

authors： Kren BT,Bandyopadhyay P,Steer CJ

更新日期：1998-03-01 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：:The human protein apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like-3G (APOBEC3G), also known as CEM-15, mediates a newly described form of innate resistance to retroviral infection by catalyzing the deamination of deoxycytidine to deoxyuridine in viral cDNA replication intermediates. Because DNA deamina...

journal_title：Nature medicine

authors： Sheehy AM,Gaddis NC,Malim MH

更新日期：2003-11-01 00:00:00

abstract：:The inwardly rectifying K(+) channel Kir6.1 forms K(+) channels by coupling with a sulfonylurea receptor in reconstituted systems, but the physiological roles of Kir6.1-containing K(+) channels have not been determined. We report here that mice lacking the gene encoding Kir6.1 (known as Kcnj8) have a high rate of sudd...

journal_title：Nature medicine

authors： Miki T,Suzuki M,Shibasaki T,Uemura H,Sato T,Yamaguchi K,Koseki H,Iwanaga T,Nakaya H,Seino S

更新日期：2002-05-01 00:00:00

abstract：:Monogenic deficiency diseases provide unique opportunities to define the contributions of individual molecules to human physiology and to identify pathologies arising from their dysfunction. Here we describe a deficiency disease in two human siblings that presented with severe bleeding, frequent infections and osteope...

journal_title：Nature medicine

authors： Malinin NL,Zhang L,Choi J,Ciocea A,Razorenova O,Ma YQ,Podrez EA,Tosi M,Lennon DP,Caplan AI,Shurin SB,Plow EF,Byzova TV

更新日期：2009-03-01 00:00:00

abstract：:Immunization of transgenic mouse models of Alzheimer disease using amyloid-beta peptide (Abeta) reduces both the Alzheimer disease-like neuropathology and the spatial memory impairments of these mice. However, a therapeutic trial of immunization with Abeta42 in humans was discontinued because a few patients developed ...

journal_title：Nature medicine

authors： McLaurin J,Cecal R,Kierstead ME,Tian X,Phinney AL,Manea M,French JE,Lambermon MH,Darabie AA,Brown ME,Janus C,Chishti MA,Horne P,Westaway D,Fraser PE,Mount HT,Przybylski M,St George-Hyslop P

更新日期：2002-11-01 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：:The severe disease atypical measles occurred when individuals immunized with a poorly protective inactivated vaccine contracted measles, and was postulated to be due to a lack of fusion-inhibiting antibodies. Here, rhesus macaques immunized with formalin-inactivated measles vaccine developed transient neutralizing and...

journal_title：Nature medicine

authors： Polack FP,Auwaerter PG,Lee SH,Nousari HC,Valsamakis A,Leiferman KM,Diwan A,Adams RJ,Griffin DE

更新日期：1999-06-01 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：:Although subtypes of pancreatic ductal adenocarcinoma (PDAC) have been described, this malignancy is clinically still treated as a single disease. Here we present patient-derived models representing the full spectrum of previously identified quasi-mesenchymal (QM-PDA), classical and exocrine-like PDAC subtypes, and id...

journal_title：Nature medicine

authors： Noll EM,Eisen C,Stenzinger A,Espinet E,Muckenhuber A,Klein C,Vogel V,Klaus B,Nadler W,Rösli C,Lutz C,Kulke M,Engelhardt J,Zickgraf FM,Espinosa O,Schlesner M,Jiang X,Kopp-Schneider A,Neuhaus P,Bahra M,Sinn BV,Eil

更新日期：2016-03-01 00:00:00

abstract：:Pten is an important phosphatase, suppressing the phosphatidylinositol-3 kinase/Akt pathway. Here, we generated adipose-specific Pten-deficient (AdipoPten-KO) mice, using newly generated Acdc promoter-driven Cre transgenic mice. AdipoPten-KO mice showed lower body and adipose tissue weights despite hyperphagia and enh...

journal_title：Nature medicine

authors： Komazawa N,Matsuda M,Kondoh G,Mizunoya W,Iwaki M,Takagi T,Sumikawa Y,Inoue K,Suzuki A,Mak TW,Nakano T,Fushiki T,Takeda J,Shimomura I

更新日期：2004-11-01 00:00:00

abstract：:Exercise has numerous health-promoting effects in humans; however, individual responsiveness to exercise with regard to endurance or metabolic health differs markedly. This 'exercise resistance' is considered to be congenital, with no evident acquired causative factors. Here we show that the anti-oxidative hepatokine ...

journal_title：Nature medicine

authors： Misu H,Takayama H,Saito Y,Mita Y,Kikuchi A,Ishii KA,Chikamoto K,Kanamori T,Tajima N,Lan F,Takeshita Y,Honda M,Tanaka M,Kato S,Matsuyama N,Yoshioka Y,Iwayama K,Tokuyama K,Akazawa N,Maeda S,Takekoshi K,Matsugo S,

更新日期：2017-04-01 00:00:00

abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

journal_title：Nature medicine

authors： He X,Lau EHY,Wu P,Deng X,Wang J,Hao X,Lau YC,Wong JY,Guan Y,Tan X,Mo X,Chen Y,Liao B,Chen W,Hu F,Zhang Q,Zhong M,Wu Y,Zhao L,Zhang F,Cowling BJ,Li F,Leung GM

更新日期：2020-09-01 00:00:00

abstract：:TRK fusions are found in a variety of cancer types, lead to oncogenic addiction, and strongly predict tumor-agnostic efficacy of TRK inhibition1-8. With the recent approval of the first selective TRK inhibitor, larotrectinib, for patients with any TRK-fusion-positive adult or pediatric solid tumor, to identify mechani...

journal_title：Nature medicine

authors： Cocco E,Schram AM,Kulick A,Misale S,Won HH,Yaeger R,Razavi P,Ptashkin R,Hechtman JF,Toska E,Cownie J,Somwar R,Shifman S,Mattar M,Selçuklu SD,Samoila A,Guzman S,Tuch BB,Ebata K,de Stanchina E,Nagy RJ,Lanman RB,

更新日期：2019-09-01 00:00:00

abstract：:Observational clinical and ex vivo studies have established a strong association between atrial fibrillation and inflammation. However, whether inflammation is the cause or the consequence of atrial fibrillation and which specific inflammatory mediators may increase the atria's susceptibility to fibrillation remain el...

journal_title：Nature medicine

authors： Rudolph V,Andrié RP,Rudolph TK,Friedrichs K,Klinke A,Hirsch-Hoffmann B,Schwoerer AP,Lau D,Fu X,Klingel K,Sydow K,Didié M,Seniuk A,von Leitner EC,Szoecs K,Schrickel JW,Treede H,Wenzel U,Lewalter T,Nickenig G,Zimmer

更新日期：2010-04-01 00:00:00

abstract：:Natural inhibitors of angiogenesis are able to block pathological neovascularization without harming the preexisting vasculature. Here we show that two such inhibitors, thrombospondin-1 and pigment epithelium-derived factor, derive specificity for remodeling vessels from their dependence on Fas/Fas ligand (FasL)-media...

journal_title：Nature medicine

authors： Volpert OV,Zaichuk T,Zhou W,Reiher F,Ferguson TA,Stuart PM,Amin M,Bouck NP

更新日期：2002-04-01 00:00:00

abstract：:Natural killer (NK) cells play an essential role in antiviral immunity, but knowledge of their function in secondary lymphoid organs is incomplete. Lymph node follicles constitute a major viral reservoir during infections with HIV-1 and simian immunodeficiency virus of macaques (SIVmac). In contrast, during nonpathoge...

journal_title：Nature medicine

authors： Huot N,Jacquelin B,Garcia-Tellez T,Rascle P,Ploquin MJ,Madec Y,Reeves RK,Derreudre-Bosquet N,Müller-Trutwin M

更新日期：2017-11-01 00:00:00

abstract：:How should clinical trials be improved? Ken Getz, a senior fellow at the Tufts Center for the Study of Drug Development, has been thinking up answers to this question for two decades. In 2003, Getz took on a new challenge when he launched the Center for Information & Study on Clinical Research, a nonprofit focused on ...

journal_title：Nature medicine

authors： Getz K

更新日期：2010-02-01 00:00:00

abstract：:Activating mutations in genes encoding G protein α (Gα) subunits occur in 4-5% of all human cancers, but oncogenic alterations in Gβ subunits have not been defined. Here we demonstrate that recurrent mutations in the Gβ proteins GNB1 and GNB2 confer cytokine-independent growth and activate canonical G protein signalin...

journal_title：Nature medicine

authors： Yoda A,Adelmant G,Tamburini J,Chapuy B,Shindoh N,Yoda Y,Weigert O,Kopp N,Wu SC,Kim SS,Liu H,Tivey T,Christie AL,Elpek KG,Card J,Gritsman K,Gotlib J,Deininger MW,Makishima H,Turley SJ,Javidi-Sharifi N,Maciejewski

更新日期：2015-01-01 00:00:00

abstract：:Hematopoietic stem and progenitor cells (HSPC) are endowed with the role of generating and maintaining lifelong the extremely diverse pool of blood cells1. Clinically, transplantation of human HSPC from an allogeneic healthy donor or infusion of autologous gene-corrected HSPC can effectively replenish defective blood ...

journal_title：Nature medicine

authors： Scala S,Basso-Ricci L,Dionisio F,Pellin D,Giannelli S,Salerio FA,Leonardelli L,Cicalese MP,Ferrua F,Aiuti A,Biasco L

更新日期：2018-11-01 00:00:00

abstract：:The adoptive transfer of T cells engineered with a chimeric antigen receptor (CAR) (hereafter referred to as CAR-T cells) specific for the B lymphocyte antigen CD19 has shown impressive clinical responses in patients with refractory B cell malignancies. However, the therapeutic effects of CAR-T cells that target other...

journal_title：Nature medicine

authors： Kagoya Y,Tanaka S,Guo T,Anczurowski M,Wang CH,Saso K,Butler MO,Minden MD,Hirano N

更新日期：2018-03-01 00:00:00

abstract：:A characteristic feature of Creutzfeldt-Jakob disease (CJD) is the accumulation in the brain of the amyloid protease-resistant protein PrPres. PrPres derives from a host-encoded, protease-sensitive isoform, PrPsen. Mutations of this protein are linked to familial variants of the disease, and the presence of a methioni...

journal_title：Nature medicine

authors： Silvestrini MC,Cardone F,Maras B,Pucci P,Barra D,Brunori M,Pocchiari M

更新日期：1997-05-01 00:00:00

abstract：:The intestine is densely populated by anaerobic commensal bacteria. These microorganisms shape immune system development, but understanding of host-commensal interactions is hampered by a lack of tools for studying the anaerobic intestinal environment. We applied metabolic oligosaccharide engineering and bioorthogonal...

journal_title：Nature medicine

authors： Geva-Zatorsky N,Alvarez D,Hudak JE,Reading NC,Erturk-Hasdemir D,Dasgupta S,von Andrian UH,Kasper DL

更新日期：2015-09-01 00:00:00