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RAN translation

Yang Li, Liurong Fang, Yanrong Zhou, Ran Tao, Dang Wang, Shaobo Xiao
Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has caused tremendous economic losses in the global swine industry since it was discovered in the late 1980s. Inducing host translation shutoff is a strategy used by many viruses to optimize their replication and spread. Here, we demonstrate that PRRSV infection causes host translation suppression, which is strongly dependent on viral replication. By screening PRRSV-encoded nonstructural proteins (nsps), we found that nsp2 participates in the induction of host translation shutoff and that its transmembrane (TM) domain is required for this process...
June 13, 2018: Journal of Virology
Tao Zu, Amrutha Pattamatta, Laura P W Ranum
More than 40 different neurological diseases are caused by microsatellite repeat expansions that locate within translated or untranslated gene regions, including 5' and 3' untranslated regions (UTRs), introns, and protein-coding regions. Expansion mutations are transcribed bidirectionally and have been shown to give rise to proteins, which are synthesized from three reading frames in the absence of an AUG initiation codon through a novel process called repeat-associated non-ATG (RAN) translation. RAN proteins, which were first described in spinocerebellar ataxia type 8 (SCA8) and myotonic dystrophy type 1 (DM1), have now been reported in a growing list of microsatellite expansion diseases...
June 11, 2018: Cold Spring Harbor Perspectives in Biology
Junshi Xu, Jonathan Wang, Nathan Hilker, Masoud Fallah-Shorshani, Marc Saleh, Ran Tu, An Wang, Laura Minet, Christos Stogios, Greg Evans, Marianne Hatzopoulou
This study presents a comparison of fleet averaged emission factors (EFs) derived from a traffic emission model with EFs estimated using plume-based measurements, including an investigation of the contribution of vehicle classes to carbon monoxide (CO), nitrogen oxides (NOx ), and elemental carbon (EC) along an urban corridor. To this end, a field campaign was conducted over one week in June 2016 on an arterial road in Toronto, Canada. Traffic data were collected using a traffic camera and a radar, while air quality was characterized using two monitoring stations: one located at ground-level and another at the rooftop of a four-storey building...
June 5, 2018: Journal of the Air & Waste Management Association
Jian Yang, Jing Yang, Yuyan Li, Yungen Xu, Chongzhao Ran
PURPOSE: Near-infrared fluorescence (NIRF) imaging has been widely used in preclinical studies; however, its low tissue penetration represents a daunting problem for translational clinical imaging of neurodegenerative diseases. The retina is known as an extension of the central nerve system (CNS), and it is widely considered as a window to the brain. Therefore, the retina can be considered as an alternative organ for investigating neurodegenerative diseases, and an eye represents an ideal NIRF imaging organ, due to its minimal opacity...
May 25, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Mark J Rapoport, Carla Zucchero Sarracini, Alex Kiss, Linda Lee, Anna Byszewski, Dallas P Seitz, Brenda Vrkljan, Frank Molnar, Nathan Herrmann, David F Tang-Wai, Christopher Frank, Blair Henry, Nicholas Pimlott, Mario Masellis, Gary Naglie
BACKGROUND: Physicians often find significant challenges in assessing automobile driving in persons with mild cognitive impairment and mild dementia and deciding when to report to transportation administrators. Care must be taken to balance the safety of patients and other road users with potential negative effects of issuing such reports. OBJECTIVE: The aim of this study was to assess whether a computer-based Driving in Dementia Decision Tool (DD-DT) increased appropriate reporting of patients with mild dementia or mild cognitive impairment to transportation administrators...
May 25, 2018: Journal of Medical Internet Research
Patrick Ming-Kuen Tang, Ying-Ying Zhang, Thomas Shiu-Kwong Mak, Philip Chiu-Tsun Tang, Xiao-Ru Huang, Hui-Yao Lan
Transforming growth factor-β (TGF-β) is the key player in tissue fibrosis. However, antifibrotic therapy targeting this multifunctional protein may interfere other physiological processes to cause side effects. Thus, precise therapeutic targets are needed to be identified by further understanding the underlying mechanisms of TGF-β1 signalling during fibrogenesis. Equilibrium of Smad signalling is crucial for TGF-β-mediated renal fibrosis, where Smad3 is pathogenic but Smad2 and Smad7 are protective. The activation of TGF-β1/Smad signalling triggers extracellular matrix deposition, and local myofibroblast generation and activation...
May 21, 2018: Journal of Physiology
Rui Jiang, Scott W Plunkett, Andrew T Ainsworth
Previous studies in different countries have shown variability in the factor structures of the Affective Style Questionnaire, possibly due to differences in cultures, translation, or statistical approaches. We ran exploratory factor analysis with oblique rotation using data from 2806 university students in Southern California. A four-factor structure was found instead of the three-factor structure found in the original Affective Style Questionnaire studies in the Northeastern United States. Support for concurrent and convergent validity was found for the Concealing and Adjusting factors...
May 1, 2018: Journal of Health Psychology
Louise L Lehrskov, Emma Dorph, Andrea M Widmer, Matthias Hepprich, Judith Siegenthaler, Katharina Timper, Marc Y Donath
OBJECTIVES: Cytokines such as IL-1 seems to play a role in the pathogenesis of fatigue associated with some chronic diseases and anti-inflammatory treatment has been shown to reduce these symptoms. Ingestion of a calorie rich meal leads to postprandial fatigue, and is associated with increased systemic concentrations of cytokines, which is more pronounced in obese than lean subjects. We investigated whether postprandial fatigue is regulated by IL-1, and therefore reduced by IL-1 antagonism, in lean and obese subjects...
April 12, 2018: Molecular Metabolism
Connor D Martin, Heather M Bool, Anthony M George, Katelyn A Carr, Leonard H Epstein, Larry W Hawk, Jerry B Richards
BACKGROUND: Stimulant drugs such as nicotine (NIC) and methylphenidate (MPH) are hypothesized to increase the reinforcing value of sensory stimuli, thus increasing the effectiveness of such reinforcers as alternatives to sucrose reinforcers. METHODS: Inbred Fischer-344 rats (n = 30) were assigned to three groups: saline (SAL; n = 10), nicotine (NIC; n = 10), or methylphenidate (MPH; n = 10). Testing was done in three phases: sucrose only, (SUC), sucrose and drug (SUC/DRUG), and sucrose, drug, and social reinforcement (SUC/DRUG/SOC)...
April 24, 2018: Psychopharmacology
Shai Elizur, Michal Berkenstadt, Liat Ries-Levavi, Noah Gruber, Orit Pinhas-Hamiel, Sharon Hassin-Baer, Annick Raas-Rothschild, Hila Raanani, Tali Cukierman-Yaffe, Raoul Orvieto, Yoram Cohen, Lidia Gabis
Fragile X Syndrome (FXS), the most common form of inherited mental retardation, is caused by a trinucleotide repeat expansion (CGG) in the 5'-untranslated region of the Fragile X Mental Retardation 1 (FMR1) gene located at Xq27.3. Patients with fragile X -related mental retardation, carry the full mutation CGG-repeat expansions (>200 CGG repeats), which are generally accompanied by hypermethylation of the promoter region, with the consequent transcriptional silencing of the FMR1 gene and absence of the encoded FMR1 protein (FMRP)...
April 2018: Harefuah
Elisabetta Soragni, Lina Petrosyan, Tommy A Rinkoski, Eric D Wieben, Keith H Baratz, Michael P Fautsch, Joel M Gottesfeld
Purpose: The strongest genetic association with Fuchs' endothelial corneal dystrophy (FECD) is the presence of an intronic (CTG·CAG)n trinucleotide repeat (TNR) expansion in the transcription factor 4 (TCF4) gene. Repeat-associated non-ATG (RAN) translation, an unconventional protein translation mechanism that does not require an initiating ATG, has been described in many TNR expansion diseases, including myotonic dystrophy type 1 (DM1). Given the similarities between DM1 and FECD, we wished to determine whether RAN translation occurs in FECD...
April 1, 2018: Investigative Ophthalmology & Visual Science
Yufei Liu, Chang Wang, Ran Wang, Yike Wu, Liang Zhang, Bi-Feng Liu, Liming Cheng, Xin Liu
Glycosylation is one of the most important post-translational modifications of protein. Recently, global profiling of human serum glycomics has become a noninvasive method for cancer-related biomarker discovery and many studies have focused on compositional glycan profiling. In contrast, structure-specific glycan profiling may provide more potential biomarkers with higher specificity than compositional profiling. In this work, N-glycans released from human serum were neutralized with methylamine and reduced by ammonia-borane complex prior to profiling using nanoLC-ESI-MS with porous graphitized carbon (PGC) and relative abundances of over 280 isomers were compared between pancreatic cancer (PC) cases (n = 32) and healthy controls (n = 32)...
June 15, 2018: Journal of Proteomics
Hailin Tang, Yuan Guo, Li Peng, Hui Fang, Zhigang Wang, Yuanyi Zheng, Haitao Ran, Yu Chen
As one of the most representative noninvasive therapeutic modalities, high-intensity focused ultrasound (HIFU) has shown great promise for cancer therapy, but its low therapeutic efficacy and biosafety significantly hinder further extensive clinical translation and application. In this work, we report on the construction of a multifunctional theranostic nanoplatform to synergistically enhance the HIFU-therapeutic efficacy based on nanomedicine. A targeted and temperature-responsive theranostic nanoplatform (PFH/DOX@PLGA/Fe3 O4 -FA) has been designed and fabricated for efficient ultrasound/magnetic resonance dual-modality imaging-guided HIFU/chemo synergistic therapy...
May 9, 2018: ACS Applied Materials & Interfaces
Cara L Croft, Brenda D Moore, Yong Ran, Paramita Chakrabarty, Yona Levites, Todd E Golde, Benoit I Giasson
Tauopathies including Alzheimer's disease and Progressive Supranuclear Palsy are a diverse group of progressive neurodegenerative disorders pathologically defined by inclusions containing aberrantly aggregated, post-translationally modified tau. The tau pathology burden correlates with neurodegeneration and dementia observed in these diseases. The microtubule binding domain of tau is essential for its physiological functions in promoting neuronal cytoskeletal stability, however it is also required for tau to assemble into an amyloid structure that comprises pathological inclusions...
2018: PloS One
Qin Chen, Rong Deng, Xian Zhao, Haihua Yuan, Hailong Zhang, Jinzhuo Dou, Ran Chen, Hui Jin, Yanli Wang, Jian Huang, Jianxiu Yu
BACKGROUND/AIMS: An increasing number of studies have linked <unterline>e</unterline>rythropoietin-<unterline>p</unterline>roducing <unterline>h</unterline>epatocellular carcinoma (Eph) family receptor tyrosine kinases to cancer progression. However, little knowledge is available about the regulation of their functions in cancer. METHODS: SUMOylation was analyzed by performing Ni2+-NTA pull-down assay and immunoprecipitation. Cell proliferation, anchorage-independent growth, and tumorigenesis in vivo were examined by cell counting kit-8, soft agar colony formation assay, and a xenograft tumor mouse model, respectively...
2018: Cellular Physiology and Biochemistry
Siddharth A Mahure, Joseph A Bosco, James D Slover, Jonathan Vigdorchik, Richard Iorio, Ran Schwarzkopf
BACKGROUND: Individuals coinfected with both hepatitis C virus (HCV) and HIV represent a unique and growing population of patients undergoing orthopaedic surgical procedures. Data regarding complications for HCV monoinfection or HIV monoinfection are robust, but there are no data available, to our knowledge, on patients who have both HCV and HIV infections. QUESTIONS/PURPOSES: We sought to determine whether patients with coinfection differed in terms of baseline demographics and comorbidity burden as compared with patients without coinfection and whether these potential differences were translated into varying levels of postoperative complications, mortality, and hospital readmission risk...
February 2018: Clinical Orthopaedics and related Research
Amrutha Swaminathan, Marilou Bouffard, Meijiang Liao, Sarah Ryan, Janis Bennion Callister, Stuart M Pickering-Brown, Gary Alan Barclay Armstrong, Pierre Drapeau
Large expansions of hexanucleotide GGGGCC (G4C2) repeats (hundreds to thousands) in the first intron of the chromosome 9 open reading frame 72 (C9orf72) locus are the strongest known genetic factor associated with amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Different hypotheses exist about the underlying disease mechanism including loss of function by haploinsufficiency, toxicity arising as a result of RNA or dipeptide repeats (DPRs). Five different DPRs are produced by repeat-associated non-ATG-initiated translation of the G4C2 repeats...
May 15, 2018: Human Molecular Genetics
Yuzhang Du, Guofang Hou, Hailong Zhang, Jinzhuo Dou, Jianfeng He, Yanming Guo, Lian Li, Ran Chen, Yanli Wang, Rong Deng, Jian Huang, Bin Jiang, Ming Xu, Jinke Cheng, Guo-Qiang Chen, Xian Zhao, Jianxiu Yu
The methyltransferase like 3 (METTL3) is a key component of the large N6-adenosine-methyltransferase complex in mammalian responsible for N6-methyladenosine (m6A) modification in diverse RNAs including mRNA, tRNA, rRNA, small nuclear RNA, microRNA precursor and long non-coding RNA. However, the characteristics of METTL3 in activation and post-translational modification (PTM) is seldom understood. Here we find that METTL3 is modified by SUMO1 mainly at lysine residues K177, K211, K212 and K215, which can be reduced by an SUMO1-specific protease SENP1...
February 28, 2018: Nucleic Acids Research
M Rebecca Glineburg, Peter K Todd, Nicolas Charlet-Berguerand, Chantal Sellier
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset inherited neurodegenerative disorder characterized by progressive intention tremor, gait ataxia and dementia associated with mild brain atrophy. The cause of FXTAS is a premutation expansion, of 55 to 200 CGG repeats localized within the 5'UTR of FMR1. These repeats are transcribed in the sense and antisense directions into mutants RNAs, which have increased expression in FXTAS. Furthermore, CGG sense and CCG antisense expanded repeats are translated into novel proteins despite their localization in putatively non-coding regions of the transcript...
February 14, 2018: Brain Research
Alexander Starr, Rita Sattler
Amyotrophic lateral sclerosis (ALS) is characterized by a progressive degeneration of upper and lower motor neurons, resulting in fatal paralysis due to denervation of the muscle. Due to genetic, pathological and symptomatic overlap, ALS is now considered a spectrum disease together with frontotemporal dementia (FTD), the second most common cause of dementia in individuals under the age of 65. Interestingly, in both diseases, there is a large prevalence of RNA binding proteins (RBPs) that are mutated and considered disease-causing, or whose dysfunction contribute to disease pathogenesis...
February 14, 2018: Brain Research
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