abstract：:Gene replacement and pre-mRNA splicing modifier therapies represent breakthrough gene targeting treatments for the neuromuscular disease spinal muscular atrophy (SMA), but mechanisms underlying variable efficacy of treatment are incompletely understood. Our examination of severe infantile onset human SMA tissues obtai...

journal_title：Science translational medicine

authors： Kong L,Valdivia DO,Simon CM,Hassinan CW,Delestrée N,Ramos DM,Park JH,Pilato CM,Xu X,Crowder M,Grzyb CC,King ZA,Petrillo M,Swoboda KJ,Davis C,Lutz CM,Stephan AH,Zhao X,Weetall M,Naryshkin NA,Crawford TO,Mentis GZ

更新日期：2021-01-27 00:00:00

abstract：:Precise form-fitting of prosthetic sockets is important for the comfort and well-being of persons with limb amputations. Capabilities for continuous monitoring of pressure and temperature at the skin-prosthesis interface can be valuable in the fitting process and in monitoring for the development of dangerous regions ...

journal_title：Science translational medicine

authors： Kwak JW,Han M,Xie Z,Chung HU,Lee JY,Avila R,Yohay J,Chen X,Liang C,Patel M,Jung I,Kim J,Namkoong M,Kwon K,Guo X,Ogle C,Grande D,Ryu D,Kim DH,Madhvapathy S,Liu C,Yang DS,Park Y,Caldwell R,Banks A,Xu S,H

更新日期：2020-12-16 00:00:00

abstract：:Neuroinflammation has been increasingly recognized to play a critical role in Alzheimer's disease (AD). The epoxy fatty acids (EpFAs) are derivatives of the arachidonic acid metabolism pathway and have anti-inflammatory activities. However, their efficacy is limited because of their rapid hydrolysis by the soluble epo...

journal_title：Science translational medicine

authors： Ghosh A,Comerota MM,Wan D,Chen F,Propson NE,Hwang SH,Hammock BD,Zheng H

更新日期：2020-12-09 00:00:00

abstract：:Late infantile Batten disease (CLN2 disease) is an autosomal recessive, neurodegenerative lysosomal storage disease caused by mutations in the CLN2 gene encoding tripeptidyl peptidase 1 (TPP1). We tested intraparenchymal delivery of AAVrh.10hCLN2, a nonhuman serotype rh.10 adeno-associated virus vector encoding human ...

journal_title：Science translational medicine

authors： Sondhi D,Kaminsky SM,Hackett NR,Pagovich OE,Rosenberg JB,De BP,Chen A,Van de Graaf B,Mezey JG,Mammen GW,Mancenido D,Xu F,Kosofsky B,Yohay K,Worgall S,Kaner RJ,Souwedaine M,Greenwald BM,Kaplitt M,Dyke JP,Ballon DJ

更新日期：2020-12-02 00:00:00

abstract：:The efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by acute and chronic graft-versus-host disease (GVHD). The impact of obesity on allo-HSCT outcomes is poorly understood. Here, we report that obesity had a negative and selective impact on acute gut GVHD after allo-HSCT in mice w...

journal_title：Science translational medicine

authors： Khuat LT,Le CT,Pai CS,Shields-Cutler RR,Holtan SG,Rashidi A,Parker SL,Knights D,Luna JI,Dunai C,Wang Z,Sturgill IR,Stoffel KM,Merleev AA,More SK,Maverakis E,Raybould HE,Chen M,Canter RJ,Monjazeb AM,Dave M,Ferrar

更新日期：2020-11-25 00:00:00

abstract：:Axonal dystrophy, indicative of perturbed axonal transport, occurs early during Alzheimer's disease (AD) pathogenesis. Little is known about the mechanisms underlying this initial sign of the pathology. This study proves that Golgi-localized γ-ear-containing ARF binding protein 3 (GGA3) loss of function, due to Gga3 g...

journal_title：Science translational medicine

authors： Lomoio S,Willen R,Kim W,Ho KZ,Robinson EK,Prokopenko D,Kennedy ME,Tanzi RE,Tesco G

更新日期：2020-11-18 00:00:00

abstract：:Adoptive cell transfer of ex vivo expanded regulatory T cells (Tregs) has shown immense potential in animal models of auto- and alloimmunity. However, the effective translation of such Treg therapies to the clinic has been slow. Because Treg homeostasis is known to require continuous T cell receptor (TCR) ligation and...

journal_title：Science translational medicine

authors： Eskandari SK,Sulkaj I,Melo MB,Li N,Allos H,Alhaddad JB,Kollar B,Borges TJ,Eskandari AS,Zinter MA,Cai S,Assaker JP,Choi JY,Al Dulaijan BS,Mansouri A,Haik Y,Tannous BA,van Son WJ,Leuvenink HGD,Pomahac B,Riella LV,

更新日期：2020-11-11 00:00:00

abstract：:There is limited information about the impact of Zika virus (ZIKV) exposure in utero on the anti-ZIKV immune responses of offspring. We infected six rhesus macaque dams with ZIKV early or late in pregnancy and studied four of their offspring over the course of a year postpartum. Despite evidence of ZIKV exposure in ut...

journal_title：Science translational medicine

authors： Vannella KM,Stein S,Connelly M,Swerczek J,Amaro-Carambot E,Coyle EM,Babyak A,Winkler CW,Saturday G,Gai ND,Hammoud DA,Dowd KA,Valencia LP,Ramos-Benitez MJ,Kindrachuk J,Pierson TC,Peterson KE,Brenchley JM,Whitehead SS,

更新日期：2020-10-28 00:00:00

abstract：:With continued advances in science and technology, there is great potential to extend our healthspan as we age. ...

journal_title：Science translational medicine

authors： Dzau VJ,Finkelman EM,Balatbat CA,Verdin EM,Pettigrew RI

更新日期：2020-10-21 00:00:00

abstract：:Defects in tumor-intrinsic interferon (IFN) signaling result in failure of immune checkpoint blockade (ICB) against cancer, but these tumors may still maintain sensitivity to T cell-based adoptive cell therapy (ACT). We generated models of IFN signaling defects in B16 murine melanoma observed in patients with acquired...

journal_title：Science translational medicine

authors： Kalbasi A,Tariveranmoshabad M,Hakimi K,Kremer S,Campbell KM,Funes JM,Vega-Crespo A,Parisi G,Champekar A,Nguyen C,Torrejon D,Shin D,Zaretsky JM,Damoiseaux RD,Speiser DE,Lopez-Casas PP,Quintero M,Ribas A

更新日期：2020-10-14 00:00:00

abstract：:Treatment of life-threatening Epstein-Barr virus (EBV)-associated tumors remains a great challenge, especially for patients with relapsed or refractory disease. Here, we found that exosomes derived from phosphoantigen-expanded Vδ2-T cells (Vδ2-T-Exos) contained death-inducing ligands (FasL and TRAIL), an activating re...

journal_title：Science translational medicine

authors： Wang X,Xiang Z,Liu Y,Huang C,Pei Y,Wang X,Zhi H,Wong WH,Wei H,Ng IO,Lee PP,Chan GC,Lau YL,Tu W

更新日期：2020-09-30 00:00:00

abstract：:Patient-derived xenografts (PDXs) and PDX-derived cells (PDCs) are useful in preclinical research. We performed a drug screening assay using PDCs and identified proteasome inhibitors as promising drugs for cholangiocarcinoma (CCA) treatment. Furthermore, we determined that phosphate and tensin homology deleted on chro...

journal_title：Science translational medicine

authors： Jiang TY,Pan YF,Wan ZH,Lin YK,Zhu B,Yuan ZG,Ma YH,Shi YY,Zeng TM,Dong LW,Tan YX,Wang HY

更新日期：2020-09-23 00:00:00

abstract：:Acquired resistance to tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) remains a clinical challenge. Especially challenging are cases in which resistance emerges through EGFR-independent mechanisms, such as through pathways that promote epithelial-to-mesenchymal transition (EMT). Through a...

journal_title：Science translational medicine

authors： Nilsson MB,Sun H,Robichaux J,Pfeifer M,McDermott U,Travers J,Diao L,Xi Y,Tong P,Shen L,Hofstad M,Kawakami M,Le X,Liu X,Fan Y,Poteete A,Hu L,Negrao MV,Tran H,Dmitrovsky E,Peng D,Gibbons DL,Wang J,Heymach JV

更新日期：2020-09-02 00:00:00

abstract：:Epithelial tissues line the organs of the body, providing an initial protective barrier as well as a surface for nutrient and drug absorption. Here, we identified enzymatic components present in the gastrointestinal epithelium that can serve as selective means for tissue-directed polymerization. We focused on the smal...

journal_title：Science translational medicine

authors： Li J,Wang T,Kirtane AR,Shi Y,Jones A,Moussa Z,Lopes A,Collins J,Tamang SM,Hess K,Shakur R,Karandikar P,Lee JS,Huang HW,Hayward A,Traverso G

更新日期：2020-08-26 00:00:00

abstract：:Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections to date has relied heavily on reverse transcription polymerase chain reaction testing. However, limited test availability, high false-negative rates, and the existence of asymptomatic or subclinical infections have resulted in an unde...

journal_title：Science translational medicine

authors： Silverman JD,Hupert N,Washburne AD

更新日期：2020-07-29 00:00:00

abstract：:Atherosclerotic lesional macrophages express molecules that promote plaque progression, but lack of mechanisms to therapeutically target these molecules represents a major gap in translational cardiovascular research. Here, we tested the efficacy of a small interfering RNA (siRNA) nanoparticle (NP) platform targeting ...

journal_title：Science translational medicine

authors： Tao W,Yurdagul A Jr,Kong N,Li W,Wang X,Doran AC,Feng C,Wang J,Islam MA,Farokhzad OC,Tabas I,Shi J

更新日期：2020-07-22 00:00:00

abstract：:Clinical advancement of the bioartificial liver is hampered by the lack of expandable human hepatocytes and appropriate bioreactors and carriers to encourage hepatic cells to function during extracorporeal circulation. We have recently developed an efficient approach for derivation of expandable liver progenitor-like ...

journal_title：Science translational medicine

authors： Li WJ,Zhu XJ,Yuan TJ,Wang ZY,Bian ZQ,Jing HS,Shi X,Chen CY,Fu GB,Huang WJ,Shi YP,Liu Q,Zeng M,Zhang HD,Wu HP,Yu WF,Zhai B,Yan HX

更新日期：2020-07-08 00:00:00

abstract：:Local delivery of anticancer agents has the potential to maximize treatment efficacy and minimize the acute and long-term systemic toxicities. Here, we used unsupervised systematic evolution of ligands by exponential enrichment to identify four RNA aptamers that specifically recognized mouse and human myeloid cells in...

journal_title：Science translational medicine

authors： De La Fuente A,Zilio S,Caroli J,Van Simaeys D,Mazza EMC,Ince TA,Bronte V,Bicciato S,Weed DT,Serafini P

更新日期：2020-06-17 00:00:00

abstract：:Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous hematological malignancy. Although immunotherapy may be an attractive modality to exploit in patients with AML, the ability to predict the groups of patients and the types of cancer that will respond to immune targeting remains limited. This st...

journal_title：Science translational medicine

authors： Vadakekolathu J,Minden MD,Hood T,Church SE,Reeder S,Altmann H,Sullivan AH,Viboch EJ,Patel T,Ibrahimova N,Warren SE,Arruda A,Liang Y,Smith TH,Foulds GA,Bailey MD,Gowen-MacDonald J,Muth J,Schmitz M,Cesano A,Pockley

更新日期：2020-06-03 00:00:00

abstract：:Nitrogen-containing bisphosphonates (N-BPs), such as alendronate, are the most widely prescribed medications for diseases involving bone, with nearly 200 million prescriptions written annually. Recently, widespread use of N-BPs has been challenged due to the risk of rare but traumatic side effects such as atypical fem...

journal_title：Science translational medicine

authors： Surface LE,Burrow DT,Li J,Park J,Kumar S,Lyu C,Song N,Yu Z,Rajagopal A,Bae Y,Lee BH,Mumm S,Gu CC,Baker JC,Mohseni M,Sum M,Huskey M,Duan S,Bijanki VN,Civitelli R,Gardner MJ,McAndrew CM,Ricci WM,Gurnett CA,D

更新日期：2020-05-20 00:00:00

abstract：:Preclinical data suggest the possibility of repurposing a drug for early intervention in envenoming by snake venom rich in metalloproteinases (Albulescu et al., this issue). ...

journal_title：Science translational medicine

authors： Koh CY,Bendre R,Kini RM

更新日期：2020-05-06 00:00:00

abstract：:Pregnancy imposes a substantial metabolic burden on women through weight gain and insulin resistance. Lactation reduces the risk of maternal postpartum diabetes, but the mechanisms underlying this benefit are unknown. Here, we identified long-term beneficial effects of lactation on β cell function, which last for year...

journal_title：Science translational medicine

authors： Moon JH,Kim H,Kim H,Park J,Choi W,Choi W,Hong HJ,Ro HJ,Jun S,Choi SH,Banerjee RR,Shong M,Cho NH,Kim SK,German MS,Jang HC,Kim H

更新日期：2020-04-29 00:00:00

abstract：:Medical devices and implants made of synthetic materials can induce an immune-mediated process when implanted in the body called the foreign body response, which results in formation of a fibrous capsule around the implant. To explore the immune and stromal connections underpinning the foreign body response, we analyz...

journal_title：Science translational medicine

authors： Chung L,Maestas DR Jr,Lebid A,Mageau A,Rosson GD,Wu X,Wolf MT,Tam AJ,Vanderzee I,Wang X,Andorko JI,Zhang H,Narain R,Sadtler K,Fan H,Čiháková D,Le Saux CJ,Housseau F,Pardoll DM,Elisseeff JH

更新日期：2020-04-15 00:00:00

abstract：:Acute tissue injury causes DNA damage and repair processes involving increased cell mitosis and polyploidization, leading to cell function alterations that may potentially drive cancer development. Here, we show that acute kidney injury (AKI) increased the risk for papillary renal cell carcinoma (pRCC) development and...

journal_title：Science translational medicine

authors： Peired AJ,Antonelli G,Angelotti ML,Allinovi M,Guzzi F,Sisti A,Semeraro R,Conte C,Mazzinghi B,Nardi S,Melica ME,De Chiara L,Lazzeri E,Lasagni L,Lottini T,Landini S,Giglio S,Mari A,Di Maida F,Antonelli A,Porpiglia F

更新日期：2020-03-25 00:00:00

abstract：:Danon disease (DD) is a rare X-linked autophagic vacuolar myopathy associated with multiorgan dysfunction, including the heart, skeletal muscle, and liver. There are no specific treatments, and most male patients die from advanced heart failure during the second or third decade of life. DD is caused by mutations in th...

journal_title：Science translational medicine

authors： Manso AM,Hashem SI,Nelson BC,Gault E,Soto-Hermida A,Villarruel E,Brambatti M,Bogomolovas J,Bushway PJ,Chen C,Battiprolu P,Keravala A,Schwartz JD,Shah G,Gu Y,Dalton ND,Hammond K,Peterson K,Saftig P,Adler ED

更新日期：2020-03-18 00:00:00

abstract：:The glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide is approved for the treatment of obesity; however, there is still much to be learned regarding the neuronal sites of action that underlie its suppressive effects on food intake and body weight. Peripherally administered liraglutide in rats acts in part ...

journal_title：Science translational medicine

authors： Fortin SM,Lipsky RK,Lhamo R,Chen J,Kim E,Borner T,Schmidt HD,Hayes MR

更新日期：2020-03-04 00:00:00

abstract：:Glucagon-like peptide-1 receptor (GLP1R) agonists and dipeptidyl peptidase 4 inhibitors are widely prescribed diabetes drugs due to their ability to stimulate insulin secretion from remaining β cells and to reduce caloric intake. Unfortunately, they fail to increase human β cell proliferation. Small-molecule inhibitor...

journal_title：Science translational medicine

authors： Ackeifi C,Wang P,Karakose E,Manning Fox JE,González BJ,Liu H,Wilson J,Swartz E,Berrouet C,Li Y,Kumar K,MacDonald PE,Sanchez R,Thorens B,DeVita R,Homann D,Egli D,Scott DK,Garcia-Ocaña A,Stewart AF

更新日期：2020-02-12 00:00:00

abstract：:Osteoclasts actively remodel both the mineral and proteinaceous components of bone during normal growth and development as well as pathologic states ranging from osteoporosis to bone metastasis. The cysteine proteinase cathepsin K confers osteoclasts with potent type I collagenolytic activity; however, cathepsin K-nul...

journal_title：Science translational medicine

authors： Zhu L,Tang Y,Li XY,Keller ET,Yang J,Cho JS,Feinberg TY,Weiss SJ

更新日期：2020-02-05 00:00:00

abstract：:Cancer-associated thrombocytosis and high concentrations of circulating transforming growth factor-β1 (TGF-β1) are frequently observed in patients with progressive cancers. Using genetic and pharmacological approaches, we show a direct link between thrombin catalytic activity and release of mature TGF-β1 from platelet...

journal_title：Science translational medicine

authors： Metelli A,Wu BX,Riesenberg B,Guglietta S,Huck JD,Mills C,Li A,Rachidi S,Krieg C,Rubinstein MP,Gewirth DT,Sun S,Lilly MB,Wahlquist AH,Carbone DP,Yang Y,Liu B,Li Z

更新日期：2020-01-08 00:00:00

abstract：:Motor neuron-specific microRNA-218 (miR-218) has recently received attention because of its roles in mouse development. However, miR-218 relevance to human motor neuron disease was not yet explored. Here, we demonstrate by neuropathology that miR-218 is abundant in healthy human motor neurons. However, in amyotrophic ...

journal_title：Science translational medicine

authors： Reichenstein I,Eitan C,Diaz-Garcia S,Haim G,Magen I,Siany A,Hoye ML,Rivkin N,Olender T,Toth B,Ravid R,Mandelbaum AD,Yanowski E,Liang J,Rymer JK,Levy R,Beck G,Ainbinder E,Farhan SMK,Lennox KA,Bode NM,Behlke MA,

更新日期：2019-12-18 00:00:00

abstract：:Systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE) of the skin are autoimmune diseases characterized by inappropriate immune responses against self-proteins; the key elements that determine disease pathogenesis and progression are largely unknown. Here, we show that mice lacking immune inhibitory...

journal_title：Science translational medicine

authors： Han X,Vesely MD,Yang W,Sanmamed MF,Badri T,Alawa J,López-Giráldez F,Gaule P,Lee SW,Zhang JP,Nie X,Nassar A,Boto A,Flies DB,Zheng L,Kim TK,Moeckel GW,McNiff JM,Chen L

更新日期：2019-12-11 00:00:00

abstract：:Cerebral cavernous malformation (CCM) is a genetic, cerebrovascular disease. Familial CCM is caused by genetic mutations in KRIT1, CCM2, or PDCD10 Disease onset is earlier and more severe in individuals with PDCD10 mutations. Recent studies have shown that lesions arise from excess mitogen-activated protein kinase kin...

journal_title：Science translational medicine

authors： Tang AT,Sullivan KR,Hong CC,Goddard LM,Mahadevan A,Ren A,Pardo H,Peiper A,Griffin E,Tanes C,Mattei LM,Yang J,Li L,Mericko-Ishizuka P,Shen L,Hobson N,Girard R,Lightle R,Moore T,Shenkar R,Polster SP,Roedel CJ,Li

更新日期：2019-11-27 00:00:00

abstract：:Patients with rheumatoid arthritis (RA) may display atypical CD21-/lo B cells in their blood, but the implication of this observation remains unclear. We report here that the group of patients with RA and elevated frequencies of CD21-/lo B cells shows decreased ataxia telangiectasia-mutated (ATM) expression and activa...

journal_title：Science translational medicine

authors： Mensah KA,Chen JW,Schickel JN,Isnardi I,Yamakawa N,Vega-Loza A,Anolik JH,Gatti RA,Gelfand EW,Montgomery RR,Horowitz MC,Craft JE,Meffre E

更新日期：2019-11-20 00:00:00

abstract：:Sepsis remains a major public health problem with no major therapeutic advances over the last several decades. The clinical and biological heterogeneity of sepsis have limited success of potential new therapies. Accordingly, there is considerable interest in developing a precision medicine approach to inform more rati...

journal_title：Science translational medicine

authors： Wong HR,Caldwell JT,Cvijanovich NZ,Weiss SL,Fitzgerald JC,Bigham MT,Jain PN,Schwarz A,Lutfi R,Nowak J,Allen GL,Thomas NJ,Grunwell JR,Baines T,Quasney M,Haileselassie B,Lindsell CJ

更新日期：2019-11-13 00:00:00

abstract：:Venetoclax is a specific B cell lymphoma 2 (BCL-2) inhibitor with promising activity against acute myeloid leukemia (AML), but its clinical efficacy as a single agent or in combination with hypomethylating agents (HMAs), such as azacitidine, is hampered by intrinsic and acquired resistance. Here, we performed a genome...

journal_title：Science translational medicine

authors： Sharon D,Cathelin S,Mirali S,Di Trani JM,Yanofsky DJ,Keon KA,Rubinstein JL,Schimmer AD,Ketela T,Chan SM

更新日期：2019-10-30 00:00:00

abstract：:Nonalcoholic fatty liver disease (NAFLD) is estimated to affect up to one-third of the general population, and new therapies are urgently required. Our laboratory previously developed a controlled-release mitochondrial protonophore (CRMP) that is functionally liver-targeted and promotes oxidation of hepatic triglyceri...

journal_title：Science translational medicine

authors： Goedeke L,Peng L,Montalvo-Romeral V,Butrico GM,Dufour S,Zhang XM,Perry RJ,Cline GW,Kievit P,Chng K,Petersen KF,Shulman GI

更新日期：2019-10-02 00:00:00

abstract：:Variants in the leucine-rich repeat kinase-2 (LRRK2) gene are associated with Parkinson's disease, leprosy, and Crohn's disease, three disorders with inflammation as an important component. Because of its high expression in granulocytes and CD68-positive cells, LRRK2 may have a function in innate immunity. We tested t...

journal_title：Science translational medicine

authors： Shutinoski B,Hakimi M,Harmsen IE,Lunn M,Rocha J,Lengacher N,Zhou YY,Khan J,Nguyen A,Hake-Volling Q,El-Kodsi D,Li J,Alikashani A,Beauchamp C,Majithia J,Coombs K,Shimshek D,Marcogliese PC,Park DS,Rioux JD,Philpott D

更新日期：2019-09-25 00:00:00

abstract：:KRAS represents an excellent therapeutic target in lung cancer, the most commonly mutated form of which can now be blocked using KRAS-G12C mutant-specific inhibitory trial drugs. Lung adenocarcinoma cells harboring KRAS mutations have been shown previously to be selectively sensitive to inhibition of mitogen-activated...

journal_title：Science translational medicine

authors： Molina-Arcas M,Moore C,Rana S,van Maldegem F,Mugarza E,Romero-Clavijo P,Herbert E,Horswell S,Li LS,Janes MR,Hancock DC,Downward J

更新日期：2019-09-18 00:00:00

abstract：:Clinical diagnostic tools requiring direct sample testing cannot be applied to infections deep within the body, and clinically available imaging tools lack specificity. New approaches are needed for early diagnosis and monitoring of bacterial infections and rapid detection of drug-resistant organisms. Molecular imagin...

journal_title：Science translational medicine

authors： Ordonez AA,Sellmyer MA,Gowrishankar G,Ruiz-Bedoya CA,Tucker EW,Palestro CJ,Hammoud DA,Jain SK

更新日期：2019-09-04 00:00:00

abstract：:Current HIV vaccines are only partially efficacious, presenting an opportunity to identify correlates of protection and, thereby, potential insight into mechanisms that prevent HIV acquisition. Two independent preclinical challenge studies in nonhuman primates (NHPs) previously showed partial efficacy of a mosaic aden...

journal_title：Science translational medicine

authors： Ehrenberg PK,Shangguan S,Issac B,Alter G,Geretz A,Izumi T,Bryant C,Eller MA,Wegmann F,Apps R,Creegan M,Bolton DL,Sekaly RP,Robb ML,Gramzinski RA,Pau MG,Schuitemaker H,Barouch DH,Michael NL,Thomas R

更新日期：2019-08-28 00:00:00