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  • 1
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    Structural determinants of an internal ribosome entry site that direct translational reading frame selection (2014)
    Oxford University Press
    Details
    Publication Date: 2014-08-15
    Description: The dicistrovirus intergenic internal ribosome entry site (IGR IRES) directly recruits the ribosome and initiates translation using a non-AUG codon. A subset of IGR IRESs initiates translation in either of two overlapping open reading frames (ORFs), resulting in expression of the 0 frame viral structural polyprotein and an overlapping +1 frame ORFx. A U–G base pair adjacent to the anticodon-like pseudoknot of the IRES directs +1 frame translation. Here, we show that the U-G base pair is not absolutely required for +1 frame translation. Extensive mutagenesis demonstrates that 0 and +1 frame translation can be uncoupled. Ribonucleic acid (RNA) structural probing analyses reveal that the mutant IRESs adopt distinct conformations. Toeprinting analysis suggests that the reading frame is selected at a step downstream of ribosome assembly. We propose a model whereby the IRES adopts conformations to occlude the 0 frame aminoacyl-tRNA thereby allowing delivery of the +1 frame aminoacyl-tRNA to the A site to initiate translation of ORFx. This study provides a new paradigm for programmed recoding mechanisms that increase the coding capacity of a viral genome.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Phospholipid transfer protein (PLTP) deficiency accelerates memory dysfunction through altering amyloid precursor protein (APP) processing in a mouse model of Alzheimer's disease (2015)
    Oxford University Press
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    Publication Date: 2015-09-12
    Description: Phospholipid transfer protein (PLTP) is a widely expressed lipid transfer protein participating in the transport of cholesterol and other lipids in the plasma and peripheral tissues. Recently, elevated amyloid β (Aβ) in young and aged PLTP-deficient brains had been reported. However, the role of PLTP in amyloid precursor protein (APP) processing and Alzheimer's disease (AD) pathology remains elusive. Here we first found that deficiency of PLTP accelerated memory dysfunction in APP/PS1E9 AD model mice at the age of 3 months. Further characterization showed that PLTP deficiency increased soluble Aβ peptides, and intracellular accumulation of Aβ was illustrated, which might be due to disrupted APP turnover and the enhanced amyloidogenic pathway. Besides, reduced brain-derived neurotrophic factor (BDNF) was found in PLTP-deficient APP/PS1E9 mice, and the BDNF level was negatively correlated with Aβ42 content, instead of Aβ40 content. In addition, autophagic dysfunction was found in the PLTP-deficient APP/PS1E9 mice. Our data presented a novel model to link phospholipid metabolism to APP processing and also suggested that PLTP played an important role in Aβ metabolism and would be useful to further elucidate functions of PLTP in AD susceptibility.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 3
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    YM500: a small RNA sequencing (smRNA-seq) database for microRNA research (2012)
    Oxford University Press
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    Publication Date: 2012-12-20
    Description: MicroRNAs (miRNAs) are small RNAs ~22 nt in length that are involved in the regulation of a variety of physiological and pathological processes. Advances in high-throughput small RNA sequencing (smRNA-seq), one of the next-generation sequencing applications, have reshaped the miRNA research landscape. In this study, we established an integrative database, the YM500 ( http://ngs.ym.edu.tw/ym500/ ), containing analysis pipelines and analysis results for 609 human and mice smRNA-seq results, including public data from the Gene Expression Omnibus (GEO) and some private sources. YM500 collects analysis results for miRNA quantification, for isomiR identification (incl. RNA editing), for arm switching discovery, and, more importantly, for novel miRNA predictions. Wetlab validation on 〉100 miRNAs confirmed high correlation between miRNA profiling and RT-qPCR results ( R = 0.84). This database allows researchers to search these four different types of analysis results via our interactive web interface. YM500 allows researchers to define the criteria of isomiRs, and also integrates the information of dbSNP to help researchers distinguish isomiRs from SNPs. A user-friendly interface is provided to integrate miRNA-related information and existing evidence from hundreds of sequencing datasets. The identified novel miRNAs and isomiRs hold the potential for both basic research and biotech applications.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    DriverDB: an exome sequencing database for cancer driver gene identification (2013)
    Oxford University Press
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    Publication Date: 2013-12-29
    Description: Exome sequencing (exome-seq) has aided in the discovery of a huge amount of mutations in cancers, yet challenges remain in converting oncogenomics data into information that is interpretable and accessible for clinical care. We constructed DriverDB ( http://ngs.ym.edu.tw/driverdb/ ), a database which incorporates 6079 cases of exome-seq data, annotation databases (such as dbSNP, 1000 Genome and Cosmic) and published bioinformatics algorithms dedicated to driver gene/mutation identification. We provide two points of view, ‘Cancer’ and ‘Gene’, to help researchers to visualize the relationships between cancers and driver genes/mutations. The ‘Cancer’ section summarizes the calculated results of driver genes by eight computational methods for a specific cancer type/dataset and provides three levels of biological interpretation for realization of the relationships between driver genes. The ‘Gene’ section is designed to visualize the mutation information of a driver gene in five different aspects. Moreover, a ‘Meta-Analysis’ function is provided so researchers may identify driver genes in customer-defined samples. The novel driver genes/mutations identified hold potential for both basic research and biotech applications.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 5
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    Effect of yeast with bacteriocin from rumen bacteria on growth performance, caecal flora, caecal fermentation and immunity function of broiler chicks (2012)
    Cambridge University Press
    Details
    Publication Date: 2012-05-08
    Description: SUMMARYThe aim of the current study was to investigate the effects of bacteriocin of Ruminococcus albus 7 that is expressed by yeast on growth performance, caecal flora, caecal fermentation and immunity function of broilers. A total of 180, one-day-old healthy broiler chicks were randomly divided into three groups: control, bacteriocin (2·5 g/kg feed) and nosiheptide (NHT) (2·5 mg/kg, as antibiotic control). Growth performance, caecal flora, caecal fermentation products and immunoglobulin (Ig) concentration were determined when chicks were 21 and 35 days old. The gene expression of avian β-defensin (AvBD) and mucin (MUC2) were measured at 35 days old. The supplementation of bacteriocin and NHT had no significant effect on body weight gain (BWG) during the experimental period. Bacteriocin supplementation significantly enhanced the growth of Lactobacillus (P
    Print ISSN: 0021-8596
    Electronic ISSN: 1469-5146
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Published by Cambridge University Press
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