Design of vaccine efficacy trials during public health emergencies.

abstract：:The importance of a broad CD8 T lymphocyte (CD8-TL) immune response to HIV is unknown. Ex vivo measurements of immunological activity directed at a limited number of defined epitopes provide an incomplete portrait of the actual immune response. We examined viral loads in simian immunodeficiency virus (SIV)-infected ma...

journal_title：Science translational medicine

authors： O'Connor SL,Lhost JJ,Becker EA,Detmer AM,Johnson RC,Macnair CE,Wiseman RW,Karl JA,Greene JM,Burwitz BJ,Bimber BN,Lank SM,Tuscher JJ,Mee ET,Rose NJ,Desrosiers RC,Hughes AL,Friedrich TC,Carrington M,O'Connor DH

更新日期：2010-03-10 00:00:00

abstract：:Sunitinib malate is a multitargeted receptor tyrosine kinase inhibitor used in the treatment of human malignancies. A substantial number of sunitinib-treated patients develop cardiac dysfunction, but the mechanism of sunitinib-induced cardiotoxicity is poorly understood. We show that mice treated with sunitinib develo...

journal_title：Science translational medicine

authors： Chintalgattu V,Rees ML,Culver JC,Goel A,Jiffar T,Zhang J,Dunner K Jr,Pati S,Bankson JA,Pasqualini R,Arap W,Bryan NS,Taegtmeyer H,Langley RR,Yao H,Kupferman ME,Entman ML,Dickinson ME,Khakoo AY

更新日期：2013-05-29 00:00:00

abstract：:Cooperative oncogenic effects resulting from the loss of PTEN and overexpression of MYC overcome the deleterious effects of endoplasmic reticulum stress not only to promote the growth of aggressive prostate cancer but also to expose a new therapy target for this disease (Nguyen et al, this issue). ...

journal_title：Science translational medicine

authors： Logothetis C,Aparicio A,Thompson TC

更新日期：2018-05-02 00:00:00

abstract：:The invasive nature of glioblastoma (GBM) represents a major clinical challenge contributing to poor outcomes. Invasion of GBM into healthy tissue restricts chemotherapeutic access and complicates surgical resection. Here, we test the hypothesis that an effective anti-invasive agent can "contain" GBM and increase the ...

journal_title：Science translational medicine

authors： Munson JM,Fried L,Rowson SA,Bonner MY,Karumbaiah L,Diaz B,Courtneidge SA,Knaus UG,Brat DJ,Arbiser JL,Bellamkonda RV

更新日期：2012-03-28 00:00:00

abstract：:The proinflammatory cytokine interleukin-1β (IL-1β) plays a central role in the pathogenesis and the course of inflammatory skin diseases, including psoriasis. Posttranscriptional activation of IL-1β is mediated by inflammasomes; however, the mechanisms triggering IL-1β processing remain unknown. Recently, cytosolic D...

journal_title：Science translational medicine

authors： Dombrowski Y,Peric M,Koglin S,Kammerbauer C,Göss C,Anz D,Simanski M,Gläser R,Harder J,Hornung V,Gallo RL,Ruzicka T,Besch R,Schauber J

更新日期：2011-05-11 00:00:00

abstract：:DEL-1 (developmental endothelial locus-1) is an endothelial cell-secreted protein that regulates LFA-1 (lymphocyte function-associated antigen-1) integrin-dependent leukocyte recruitment and inflammation in various tissues. We identified a novel regulatory mechanism of DEL-1 in osteoclast biology. Specifically, we sho...

journal_title：Science translational medicine

authors： Shin J,Maekawa T,Abe T,Hajishengallis E,Hosur K,Pyaram K,Mitroulis I,Chavakis T,Hajishengallis G

更新日期：2015-09-30 00:00:00

abstract：:Hutchinson-Gilford progeria syndrome (HGPS) is caused by a point mutation in the LMNA gene that activates a cryptic donor splice site and yields a truncated form of prelamin A called progerin. Small amounts of progerin are also produced during normal aging. Studies with mouse models of HGPS have allowed the recent dev...

journal_title：Science translational medicine

authors： Osorio FG,Navarro CL,Cadiñanos J,López-Mejía IC,Quirós PM,Bartoli C,Rivera J,Tazi J,Guzmán G,Varela I,Depetris D,de Carlos F,Cobo J,Andrés V,De Sandre-Giovannoli A,Freije JM,Lévy N,López-Otín C

更新日期：2011-10-26 00:00:00

abstract：:Centronuclear myopathies (CNMs) are severe diseases characterized by muscle weakness and myofiber atrophy. Currently, there are no approved treatments for these disorders. Mutations in the phosphoinositide 3-phosphatase myotubularin (MTM1) are responsible for X-linked CNM (XLCNM), also called myotubular myopathy, wher...

journal_title：Science translational medicine

authors： Lionello VM,Nicot AS,Sartori M,Kretz C,Kessler P,Buono S,Djerroud S,Messaddeq N,Koebel P,Prokic I,Hérault Y,Romero NB,Laporte J,Cowling BS

更新日期：2019-03-20 00:00:00

abstract：:Sporadic inclusion body myositis (sIBM) is the commonest severe myopathy in patients more than 50 years of age. Previous therapeutic trials have targeted the inflammatory features of sIBM but all have failed. Because protein dyshomeostasis may also play a role in sIBM, we tested the effects of targeting this feature o...

journal_title：Science translational medicine

authors： Ahmed M,Machado PM,Miller A,Spicer C,Herbelin L,He J,Noel J,Wang Y,McVey AL,Pasnoor M,Gallagher P,Statland J,Lu CH,Kalmar B,Brady S,Sethi H,Samandouras G,Parton M,Holton JL,Weston A,Collinson L,Taylor JP,Schia

更新日期：2016-03-23 00:00:00

abstract：:Misuse of prescription opioids, opioid addiction, and overdose underscore the urgent need for developing addiction-free effective medications for treating severe pain. Mu opioid peptide (MOP) receptor agonists provide very effective pain relief. However, severe side effects limit their use in the clinical setting. Ago...

journal_title：Science translational medicine

authors： Ding H,Kiguchi N,Yasuda D,Daga PR,Polgar WE,Lu JJ,Czoty PW,Kishioka S,Zaveri NT,Ko MC

更新日期：2018-08-29 00:00:00

abstract：:In humans, exposure to aristolochic acid (AA) is associated with urothelial carcinoma of the upper urinary tract (UTUC). Exome sequencing of UTUCs from 19 individuals with documented exposure to AA revealed a remarkably large number of somatic mutations and an unusual mutational signature attributable to AA. Most of t...

journal_title：Science translational medicine

authors： Hoang ML,Chen CH,Sidorenko VS,He J,Dickman KG,Yun BH,Moriya M,Niknafs N,Douville C,Karchin R,Turesky RJ,Pu YS,Vogelstein B,Papadopoulos N,Grollman AP,Kinzler KW,Rosenquist TA

更新日期：2013-08-07 00:00:00

abstract：:Fibroblasts are primary cellular protagonists of wound healing. They also exhibit circadian timekeeping, which imparts an approximately 24-hour rhythm to their biological function. We interrogated the functional consequences of the cell-autonomous clockwork in fibroblasts using a proteome-wide screen for rhythmically ...

journal_title：Science translational medicine

authors： Hoyle NP,Seinkmane E,Putker M,Feeney KA,Krogager TP,Chesham JE,Bray LK,Thomas JM,Dunn K,Blaikley J,O'Neill JS

更新日期：2017-11-08 00:00:00

abstract：:Tuberculous meningitis (TBM) is a devastating form of tuberculosis (TB), and key TB antimicrobials, including rifampin, have restricted brain penetration. A lack of reliable data on intralesional drug biodistribution in infected tissues has limited pharmacokinetic (PK) modeling efforts to optimize TBM treatments. Curr...

journal_title：Science translational medicine

authors： Tucker EW,Guglieri-Lopez B,Ordonez AA,Ritchie B,Klunk MH,Sharma R,Chang YS,Sanchez-Bautista J,Frey S,Lodge MA,Rowe SP,Holt DP,Gobburu JVS,Peloquin CA,Mathews WB,Dannals RF,Pardo CA,Kannan S,Ivaturi VD,Jain SK

更新日期：2018-12-05 00:00:00

abstract：:Metastasis is the major cause of cancer mortality. A more thorough understanding of the mechanisms driving this complex multistep process will aid in the identification and characterization of therapeutically targetable genetic drivers of disease progression. We demonstrate that KLF6-SV1, an oncogenic splice variant o...

journal_title：Science translational medicine

authors： Hatami R,Sieuwerts AM,Izadmehr S,Yao Z,Qiao RF,Papa L,Look MP,Smid M,Ohlssen J,Levine AC,Germain D,Burstein D,Kirschenbaum A,DiFeo A,Foekens JA,Narla G

更新日期：2013-01-23 00:00:00

abstract：:Canavan disease is a hereditary leukodystrophy caused by mutations in the aspartoacylase gene (ASPA), leading to loss of enzyme activity and increased concentrations of the substrate N-acetyl-aspartate (NAA) in the brain. Accumulation of NAA results in spongiform degeneration of white matter and severe impairment of p...

journal_title：Science translational medicine

authors： Leone P,Shera D,McPhee SW,Francis JS,Kolodny EH,Bilaniuk LT,Wang DJ,Assadi M,Goldfarb O,Goldman HW,Freese A,Young D,During MJ,Samulski RJ,Janson CG

更新日期：2012-12-19 00:00:00

abstract：:Disease-free infection in HIV-infected adults is associated with human leukocyte antigen-mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors preventing HIV disease, we i...

journal_title：Science translational medicine

authors： Muenchhoff M,Adland E,Karimanzira O,Crowther C,Pace M,Csala A,Leitman E,Moonsamy A,McGregor C,Hurst J,Groll A,Mori M,Sinmyee S,Thobakgale C,Tudor-Williams G,Prendergast AJ,Kloverpris H,Roider J,Leslie A,Shingadia D

更新日期：2016-09-28 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：:Prenatal and postnatal treatment with a CFTR modifier attenuates pathological changes in a ferret model of cystic fibrosis (Sun et al., this issue). ...

journal_title：Science translational medicine

authors： Ferkol TW

更新日期：2019-03-27 00:00:00

abstract：:Osteoarthritis (OA) is a common degenerative condition that afflicts more than 70% of the population between 55 and 77 years of age. Although its prevalence is rising globally with aging of the population, current therapy is limited to symptomatic relief and, in severe cases, joint replacement surgery. We report that ...

journal_title：Science translational medicine

authors： Ruan MZ,Erez A,Guse K,Dawson B,Bertin T,Chen Y,Jiang MM,Yustein J,Gannon F,Lee BH

更新日期：2013-03-13 00:00:00

abstract：:Each year, more than a half million people in the United States alone die from sepsis, a dire multisystem disease with highly inadequate treatment options. In a recent issue of Science, Puneet and colleagues provide compelling evidence that inhibiting sphingosine kinase 1--an enzyme that resides in immune cells and is...

journal_title：Science translational medicine

authors： O'Neill LA

更新日期：2010-06-16 00:00:00

abstract：:The epidermal growth factor receptor (EGFR) plays an important role in tissue homeostasis and tumor progression. However, cancer patients treated with EGFR inhibitors (EGFRIs) frequently develop acneiform skin toxicities, which are a strong predictor of a patient's treatment response. We show that the early inflammato...

journal_title：Science translational medicine

authors： Lichtenberger BM,Gerber PA,Holcmann M,Buhren BA,Amberg N,Smolle V,Schrumpf H,Boelke E,Ansari P,Mackenzie C,Wollenberg A,Kislat A,Fischer JW,Röck K,Harder J,Schröder JM,Homey B,Sibilia M

更新日期：2013-08-21 00:00:00

abstract：:The brain is emerging as an important regulator of systemic glucose metabolism. Accumulating data from animal and observational human studies suggest that striatal dopamine signaling plays a role in glucose regulation, but direct evidence in humans is currently lacking. We present a series of experiments supporting th...

journal_title：Science translational medicine

authors： Ter Horst KW,Lammers NM,Trinko R,Opland DM,Figee M,Ackermans MT,Booij J,van den Munckhof P,Schuurman PR,Fliers E,Denys D,DiLeone RJ,la Fleur SE,Serlie MJ

更新日期：2018-05-23 00:00:00

abstract：:Sleep disorders are highly prevalent in patients with traumatic brain injury (TBI) and can significantly impair cognitive rehabilitation. No proven therapies exist to mitigate the neurocognitive consequences of TBI. We show that mild brain injury in mice causes a persistent inability to maintain wakefulness and decrea...

journal_title：Science translational medicine

authors： Lim MM,Elkind J,Xiong G,Galante R,Zhu J,Zhang L,Lian J,Rodin J,Kuzma NN,Pack AI,Cohen AS

更新日期：2013-12-11 00:00:00

abstract：:Functionally diverse subpopulations of astrocytes have correlates in the neoplastic adult brain. ...

journal_title：Science translational medicine

authors： Venere M

更新日期：2017-03-01 00:00:00

abstract：:Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. The most common CF-associated mutation is ΔF508, which deletes a phenylalanine in position 508. In vitro studies indicate that the resultant prot...

journal_title：Science translational medicine

authors： Ostedgaard LS,Meyerholz DK,Chen JH,Pezzulo AA,Karp PH,Rokhlina T,Ernst SE,Hanfland RA,Reznikov LR,Ludwig PS,Rogan MP,Davis GJ,Dohrn CL,Wohlford-Lenane C,Taft PJ,Rector MV,Hornick E,Nassar BS,Samuel M,Zhang Y,Richt

更新日期：2011-03-16 00:00:00

abstract：:Most cancer deaths arise from metastases as a result of circulating tumor cells (CTCs) spreading from the primary tumor to vital organs. Despite progress in cancer prognosis, the role of CTCs in early disease diagnosis is unclear because of the low sensitivity of CTC assays. We demonstrate the high sensitivity of the ...

journal_title：Science translational medicine

authors： Galanzha EI,Menyaev YA,Yadem AC,Sarimollaoglu M,Juratli MA,Nedosekin DA,Foster SR,Jamshidi-Parsian A,Siegel ER,Makhoul I,Hutchins LF,Suen JY,Zharov VP

更新日期：2019-06-12 00:00:00

abstract：:Recent studies have established the involvement of the fat mass and obesity-associated gene (FTO) in metabolic disorders such as obesity and diabetes. However, the precise molecular mechanism by which FTO regulates metabolism remains unknown. Here, we used a structure-based virtual screening of U.S. Food and Drug Admi...

journal_title：Science translational medicine

authors： Peng S,Xiao W,Ju D,Sun B,Hou N,Liu Q,Wang Y,Zhao H,Gao C,Zhang S,Cao R,Li P,Huang H,Ma Y,Wang Y,Lai W,Ma Z,Zhang W,Huang S,Wang H,Zhang Z,Zhao L,Cai T,Zhao YL,Wang F,Nie Y,Zhi G,Yang YG,Zhang EE,

更新日期：2019-04-17 00:00:00

abstract：:A skin-penetrant small molecule activates melanin production to protect cells from cancer-inducing ultraviolet damage. ...

journal_title：Science translational medicine

authors： Venere M

更新日期：2017-07-05 00:00:00

abstract：:Biallelic mutations in ABCC6 cause pseudoxanthoma elasticum (PXE), a disease characterized by calcification in the skin, eyes, and blood vessels. The function of ATP-binding cassette C6 (ABCC6) and the pathogenesis of PXE remain unclear. We used mouse models and patient fibroblasts to demonstrate genetic interaction a...

journal_title：Science translational medicine

authors： Ziegler SG,Ferreira CR,MacFarlane EG,Riddle RC,Tomlinson RE,Chew EY,Martin L,Ma CT,Sergienko E,Pinkerton AB,Millán JL,Gahl WA,Dietz HC

更新日期：2017-06-07 00:00:00

abstract：:Advances in understanding the genetics and underlying pathology of the catastrophic childhood epilepsies are pointing toward treatments. ...

journal_title：Science translational medicine

authors： Katsnelson A,Buzsáki G,Swann JW

更新日期：2014-11-12 00:00:00