Gga3 deletion and a GGA3 rare variant associated with late onset Alzheimer's disease trigger BACE1 accumulation in axonal swellings.

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：:Inhaled drugs offer advantages, such as rapid onset of action, but require formulations and delivery systems that reproducibly and conveniently administer the drug. CVT-301 is a powder formulation of levodopa delivered by a breath-actuated inhaler that has been developed for treating OFF episodes (motor fluctuations b...

journal_title：Science translational medicine

authors： Lipp MM,Batycky R,Moore J,Leinonen M,Freed MI

更新日期：2016-10-12 00:00:00

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：:We tested the hypothesis that ex vivo hepatocyte gene therapy can correct the metabolic disorder in fumarylacetoacetate hydrolase-deficient (Fah(-/-)) pigs, a large animal model of hereditary tyrosinemia type 1 (HT1). Recipient Fah(-/-) pigs underwent partial liver resection and hepatocyte isolation by collagenase dig...

journal_title：Science translational medicine

authors： Hickey RD,Mao SA,Glorioso J,Elgilani F,Amiot B,Chen H,Rinaldo P,Marler R,Jiang H,DeGrado TR,Suksanpaisan L,O'Connor MK,Freeman BL,Ibrahim SH,Peng KW,Harding CO,Ho CS,Grompe M,Ikeda Y,Lillegard JB,Russell SJ,Nybe

更新日期：2016-07-27 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：: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：:Magnetic resonance imaging (MRI) is a powerful diagnostic tool, but its use is restricted to the scanner suite. Here, we demonstrate that a bedside nuclear magnetic resonance (NMR) sensor can assess fluid status changes in individuals at a fraction of the time and cost compared to MRI. Our study recruited patients wit...

journal_title：Science translational medicine

authors： Colucci LA,Corapi KM,Li M,Parada XV,Allegretti AS,Lin HY,Ausiello DA,Rosen MS,Cima MJ

更新日期：2019-07-24 00:00:00

abstract：:As observed during the 2013-2016 Ebola virus disease epidemic, containment of filovirus outbreaks is challenging and made more difficult by the lack of approved vaccine or therapeutic options. Marburg and Ravn viruses are highly virulent and cause severe and frequently lethal disease in humans. Monoclonal antibodies (...

journal_title：Science translational medicine

authors： Mire CE,Geisbert JB,Borisevich V,Fenton KA,Agans KN,Flyak AI,Deer DJ,Steinkellner H,Bohorov O,Bohorova N,Goodman C,Hiatt A,Kim DH,Pauly MH,Velasco J,Whaley KJ,Crowe JE Jr,Zeitlin L,Geisbert TW

更新日期：2017-04-05 00:00:00

abstract：:In current clinical practice, uterine contractions are monitored via a tocodynamometer or an intrauterine pressure catheter, both of which provide crude information about contractions. Although electrohysterography/electromyography can measure uterine electrical activity, this method lacks spatial specificity and thus...

journal_title：Science translational medicine

authors： Wu W,Wang H,Zhao P,Talcott M,Lai S,McKinstry RC,Woodard PK,Macones GA,Schwartz AL,Cahill AG,Cuculich PS,Wang Y

更新日期：2019-03-13 00:00:00

abstract：:Case fatality rates for severe malaria remain high even in the best clinical settings because antimalarial drugs act against the parasite without alleviating life-threatening inflammation. We assessed the potential for host-directed therapy of severe malaria of a new class of anti-inflammatory drugs, the innate defens...

journal_title：Science translational medicine

authors： Achtman AH,Pilat S,Law CW,Lynn DJ,Janot L,Mayer ML,Ma S,Kindrachuk J,Finlay BB,Brinkman FS,Smyth GK,Hancock RE,Schofield L

更新日期：2012-05-23 00:00:00

abstract：:Retention and use, without explicit parental permission, of residual dried blood samples from newborn screening has generated public controversy over concerns about violations of family privacy rights and loss of parental autonomy. The public debate about this issue has included little discussion a...

journal_title：Science translational medicine

authors： Lewis MH,Scheurer ME,Green RC,McGuire AL

更新日期：2012-11-07 00:00:00

abstract：:The Wnt signaling pathway plays a central role in bone development and homeostasis. In most cases, Wnt ligands promote bone growth, which has led to speculation that Wnt factors could be used to stimulate bone healing. We gained insights into the mechanism by which Wnt signaling regulates adult bone repair through the...

journal_title：Science translational medicine

authors： Minear S,Leucht P,Jiang J,Liu B,Zeng A,Fuerer C,Nusse R,Helms JA

更新日期：2010-04-28 00:00:00

abstract：:High-grade B cell lymphomas with concurrent activation of the MYC and BCL2 oncogenes, also known as double-hit lymphomas (DHL), show dismal prognosis with current therapies. MYC activation sensitizes cells to inhibition of mitochondrial translation by the antibiotic tigecycline, and treatment with this compound provid...

journal_title：Science translational medicine

authors： Ravà M,D'Andrea A,Nicoli P,Gritti I,Donati G,Doni M,Giorgio M,Olivero D,Amati B

更新日期：2018-01-31 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：: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：: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：:SORLA/SORL1 is a unique neuronal sorting receptor for the amyloid precursor protein that has been causally implicated in both sporadic and autosomal dominant familial forms of Alzheimer's disease (AD). Brain concentrations of SORLA are inversely correlated with amyloid-β (Aβ) in mouse models and AD patients, suggestin...

journal_title：Science translational medicine

authors： Caglayan S,Takagi-Niidome S,Liao F,Carlo AS,Schmidt V,Burgert T,Kitago Y,Füchtbauer EM,Füchtbauer A,Holtzman DM,Takagi J,Willnow TE

更新日期：2014-02-12 00:00:00

abstract：:Spinal cord injury (SCI) is typically complicated by progressive hemorrhagic necrosis, an autodestructive process of secondary injury characterized by progressive enlargement of a hemorrhagic contusion during the first several hours after trauma. We assessed the role of Abcc8, which encodes sulfonylurea receptor 1 (SU...

journal_title：Science translational medicine

authors： Simard JM,Woo SK,Norenberg MD,Tosun C,Chen Z,Ivanova S,Tsymbalyuk O,Bryan J,Landsman D,Gerzanich V

更新日期：2010-04-21 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：:Reactivation of fetal hemoglobin (HbF) is being pursued as a treatment strategy for hemoglobinopathies. Here, we evaluated the therapeutic potential of hematopoietic stem and progenitor cells (HSPCs) edited with the CRISPR-Cas9 nuclease platform to recapitulate naturally occurring mutations identified in individuals w...

journal_title：Science translational medicine

authors： Humbert O,Radtke S,Samuelson C,Carrillo RR,Perez AM,Reddy SS,Lux C,Pattabhi S,Schefter LE,Negre O,Lee CM,Bao G,Adair JE,Peterson CW,Rawlings DJ,Scharenberg AM,Kiem HP

更新日期：2019-07-31 00:00:00

abstract：:Recent studies highlighted long noncoding RNAs (lncRNAs) to play an important role in cardiac development. However, understanding of lncRNAs in cardiac diseases is still limited. Global lncRNA expression profiling indicated that several lncRNA transcripts are deregulated during pressure overload-induced cardiac hypert...

journal_title：Science translational medicine

authors： Viereck J,Kumarswamy R,Foinquinos A,Xiao K,Avramopoulos P,Kunz M,Dittrich M,Maetzig T,Zimmer K,Remke J,Just A,Fendrich J,Scherf K,Bolesani E,Schambach A,Weidemann F,Zweigerdt R,de Windt LJ,Engelhardt S,Dandekar T,

更新日期：2016-02-17 00:00:00

abstract：:Nipah virus is an emerging pathogen in the Paramyxoviridae family. Upon transmission of Nipah virus from its natural reservoir, Pteropus spp. fruit bats, to humans, it causes respiratory and neurological disease with a case-fatality rate about 70%. Human-to-human transmission has been observed during Nipah virus outbr...

journal_title：Science translational medicine

authors： Lo MK,Feldmann F,Gary JM,Jordan R,Bannister R,Cronin J,Patel NR,Klena JD,Nichol ST,Cihlar T,Zaki SR,Feldmann H,Spiropoulou CF,de Wit E

更新日期：2019-05-29 00:00:00

abstract：:Short-term starvation (or fasting) protects normal cells, mice, and potentially humans from the harmful side effects of a variety of chemotherapy drugs. Here, we show that treatment with starvation conditions sensitized yeast cells (Saccharomyces cerevisiae) expressing the oncogene-like RAS2(val19) to oxidative stress...

journal_title：Science translational medicine

authors： Lee C,Raffaghello L,Brandhorst S,Safdie FM,Bianchi G,Martin-Montalvo A,Pistoia V,Wei M,Hwang S,Merlino A,Emionite L,de Cabo R,Longo VD

更新日期：2012-03-07 00:00:00

abstract：:Long synthetic peptides (LSPs) have a variety of important clinical uses as synthetic vaccines and drugs. Techniques for peptide synthesis were revolutionized in the 1960s and 1980s, after which efficient techniques for purification and characterization of the product were developed. These improved techniques allowed ...

journal_title：Science translational medicine

authors： Corradin G,Kajava AV,Verdini A

更新日期：2010-09-22 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：: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：:People with autism spectrum disorder (ASD) are characterized by deficits in social interaction, language, and behavioral flexibility. Rare mutations and copy number variations have been identified in individuals with ASD, but in most patients, the causal variants remain unknown. A genome-wide association study (GWAS),...

journal_title：Science translational medicine

authors： Kerin T,Ramanathan A,Rivas K,Grepo N,Coetzee GA,Campbell DB

更新日期：2012-04-04 00:00:00

abstract：:Because of the well-established therapeutic benefit of boosting antitumor responses through blockade of the T cell inhibitory receptor PD-1, it has been proposed that PD-1 blockade could also be useful in infectious disease settings, including Mycobacterium tuberculosis (Mtb) infection. However, in preclinical models,...

journal_title：Science translational medicine

authors： Barber DL,Sakai S,Kudchadkar RR,Fling SP,Day TA,Vergara JA,Ashkin D,Cheng JH,Lundgren LM,Raabe VN,Kraft CS,Nieva JJ,Cheever MA,Nghiem PT,Sharon E

更新日期：2019-01-16 00:00:00

abstract：:Limited treatment options exist for patients who suffer from a painful bladder condition known as interstitial cystitis/bladder pain syndrome (IC/BPS). Whether given systemically (orally) or by short-duration (1 to 2 hours) exposure via intravesical instillation, therapeutic agents have exhibited poor efficacy because...

journal_title：Science translational medicine

authors： Nickel JC,Jain P,Shore N,Anderson J,Giesing D,Lee H,Kim G,Daniel K,White S,Larrivee-Elkins C,Lekstrom-Himes J,Cima M

更新日期：2012-07-18 00:00:00

abstract：:Acquired lymphedema is a cancer sequela and a global health problem currently lacking pharmacologic therapy. We have previously demonstrated that ketoprofen, an anti-inflammatory agent with dual 5-lipoxygenase and cyclooxygenase inhibitory properties, effectively reverses histopathology in experimental lymphedema. We ...

journal_title：Science translational medicine

authors： Tian W,Rockson SG,Jiang X,Kim J,Begaye A,Shuffle EM,Tu AB,Cribb M,Nepiyushchikh Z,Feroze AH,Zamanian RT,Dhillon GS,Voelkel NF,Peters-Golden M,Kitajewski J,Dixon JB,Nicolls MR

更新日期：2017-05-10 00:00:00