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  • 1
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    Gene expression profiles of putative biomarker candidates in Mycobacterium avium subsp. paratuberculosis-infected cattle (2016)
    Oxford University Press
    Details
    Publication Date: 2016-04-23
    Description: This study was conducted to analyze the gene expression of prognostic potential biomarker candidates using the whole blood of cattle naturally infected with Mycobacterium avium subsp. paratuberculosis (MAP). We conducted real-time PCR to evaluate 23 potential biomarker candidates. Experimental animals were divided into four groups based on fecal MAP PCR and serum ELISA. Seven ( KLRB1 , HGF , MPO , LTF , SERPINE1 , S100A8 and S100A9 ) genes were up-regulated in fecal MAP-positive cattle and three ( KLRB1 , MPO and S100A9 ) were up-regulated in MAP-seropositive cattle relative to uninfected cattle. In subclinically infected animals, 17 genes ( TFRC , S100A8 , S100A9 , MPO , GBP6 , LTF , KLRB1 , SERPINE1 , PIGR , IL-10 , CXCR3 , CD14 , MMP9 , ELANE , CHI3L1 , HP and HGF ) were up-regulated compared with the control group. Moreover, six genes ( CXCR3 , HP , HGF , LTF , TFRC and GBP6 ) showed significant differences between experimental groups. Taken together, our data suggest that six genes ( LTF , HGF , HP , CXCR3 , GBP6 and TFRC ) played essential roles in the immune response to MAP during the subclinical stage and therefore might be useful as prognostic biomarkers.
    Print ISSN: 0928-8244
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 2
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    Positive Selection on a Regulatory Insertion-Deletion Polymorphism in FADS2 Influences Apparent Endogenous Synthesis of Arachidonic Acid (2016)
    Oxford University Press
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    Publication Date: 2016-06-22
    Description: Long chain polyunsaturated fatty acids (LCPUFA) are bioactive components of membrane phospholipids and serve as substrates for signaling molecules. LCPUFA can be obtained directly from animal foods or synthesized endogenously from 18 carbon precursors via the FADS2 coded enzyme. Vegans rely almost exclusively on endogenous synthesis to generate LCPUFA and we hypothesized that an adaptive genetic polymorphism would confer advantage. The rs66698963 polymorphism, a 22-bp insertion–deletion within FADS2 , is associated with basal FADS1 expression, and coordinated induction of FADS1 and FADS2 in vitro. Here, we determined rs66698963 genotype frequencies from 234 individuals of a primarily vegetarian Indian population and 311 individuals from the US. A much higher I/I genotype frequency was found in Indians (68%) than in the US (18%). Analysis using 1000 Genomes Project data confirmed our observation, revealing a global I/I genotype of 70% in South Asians, 53% in Africans, 29% in East Asians, and 17% in Europeans. Tests based on population divergence, site frequency spectrum, and long-range haplotype consistently point to positive selection encompassing rs66698963 in South Asian, African, and some East Asian populations. Basal plasma phospholipid arachidonic acid (ARA) status was 8% greater in I/I compared with D/D individuals. The biochemical pathway product–precursor difference, ARA minus linoleic acid, was 31% and 13% greater for I/I and I/D compared with D/D, respectively. This study is consistent with previous in vitro data suggesting that the insertion allele enhances n-6 LCPUFA synthesis and may confer an adaptive advantage in South Asians because of the traditional plant-based diet practice.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 3
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    CPAT: Coding-Potential Assessment Tool using an alignment-free logistic regression model (2013)
    Oxford University Press
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    Publication Date: 2013-04-02
    Description: Thousands of novel transcripts have been identified using deep transcriptome sequencing. This discovery of large and ‘hidden’ transcriptome rejuvenates the demand for methods that can rapidly distinguish between coding and noncoding RNA. Here, we present a novel alignment-free method, Coding Potential Assessment Tool (CPAT), which rapidly recognizes coding and noncoding transcripts from a large pool of candidates. To this end, CPAT uses a logistic regression model built with four sequence features: open reading frame size, open reading frame coverage, Fickett TESTCODE statistic and hexamer usage bias. CPAT software outperformed (sensitivity: 0.96, specificity: 0.97) other state-of-the-art alignment-based software such as Coding-Potential Calculator (sensitivity: 0.99, specificity: 0.74) and Phylo Codon Substitution Frequencies (sensitivity: 0.90, specificity: 0.63). In addition to high accuracy, CPAT is approximately four orders of magnitude faster than Coding-Potential Calculator and Phylo Codon Substitution Frequencies, enabling its users to process thousands of transcripts within seconds. The software accepts input sequences in either FASTA- or BED-formatted data files. We also developed a web interface for CPAT that allows users to submit sequences and receive the prediction results almost instantly.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    Exploring sRNA-mediated gene silencing mechanisms using artificial small RNAs derived from a natural RNA scaffold in Escherichia coli (2013)
    Oxford University Press
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    Publication Date: 2013-04-02
    Description: An artificial small RNA (afsRNA) scaffold was designed from an Escherichia coli sRNA, SibC. Using the lacZ reporter system, the gene silencing effects of afsRNAs were examined to explore the sRNA-mediated gene-silencing mechanisms in E. coli . Substitution of the original target recognition sequence with a new sequence recognizing lacZ mRNA led to effective reduction of lacZ gene expression. Single-strandedness of the target recognition sequences in the scaffold was essential for effective gene silencing. The target recognition sequence was shortened to 10 nt without significant loss of gene silencing, although this minimal length was limited to a specific target mRNA sequence. In cases where afsRNAs had mismatched (forming internal loops) or unmatched (forming bulges) regions in the middle of the target recognition sequence, internal loop-forming afsRNAs were more effective in gene silencing than those that formed bulges. Unexpectedly, gene silencing by afsRNA was not decreased but increased on hfq disruption in E. coli , particularly when interactions between afsRNA and mRNA were weak, suggesting that Hfq is possibly involved in destabilization of the RNA–RNA duplex, rather than enhancement of base pairing.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 5
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    The role of the adductor muscle as an energy storage organ in the pen shell Atrina japonica (Reeve, 1858) (2015)
    Oxford University Press
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    Publication Date: 2015-10-24
    Description: The biochemical composition and reproductive cycle of the pen shell Atrina japonica were investigated through separate analyses of the adductor muscle, gonad and the remaining tissues over a 1-year cycle. Seasonal variations in condition and gonadosomatic indices reflected those of gross weights of biochemical components of whole tissues. During the spring period, growth was initiated in the gonadal tissues simultaneously with the maximum weight gain in the adductor muscle, in which most of the energy reserves were stored, indicating that gametogenesis occurs at the expense of immediately ingested food energy. The increased energy reserves in the gonad during gametogenic development were exhausted completely during the summer spawning. Protein and carbohydrate reserves in the adductor muscle were used as catabolic substrates during spawning. The interannual shift in the timing of spawning appeared to be related to the changes in energy storage and gamete growth during the spring, probably reflecting changes in nutritional conditions in the ambient environment. Our results suggest that the adductor muscle of the pen shell plays a critical role as a major organ responsible for energy storage and that organ-specific biochemical composition can provide information of general relevance to the processes of energy gain and mobilization in bivalves.
    Print ISSN: 0260-1230
    Electronic ISSN: 1464-3766
    Topics: Biology
    Published by Oxford University Press
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  • 6
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    MACE: mutation-oriented profiling of chemical response and gene expression in cancers (2015)
    Oxford University Press
    Details
    Publication Date: 2015-04-28
    Description: : The mutational status of specific cancer lineages can affect the sensitivity to or resistance against cancer drugs. The MACE database provides web-based interactive tools for interpreting large chemical screening and gene expression datasets of cancer cell lines in terms of mutation and lineage categories. GI50 data of chemicals against individual NCI60 cell lines were normalized and organized to statistically identify mutation- or lineage-specific chemical responses. Similarly, DNA microarray data on NCI60 cell lines were processed to analyze mutation- or lineage-specific gene expression signatures. A combined analysis of GI50 and gene expression data to find potential associations between chemicals and genes is also a capability of this system. This database will provide extensive, systematic information to identify lineage- or mutation-specific anticancer agents and related gene targets. Availability and implementation: The MACE web database is available at http://mace.sookmyung.ac.kr/ . Supplementary information : Supplementary data are available at Bioinformatics online. Contact: yoonsj@sookmyung.ac.kr
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 7
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    HiXCorr: a portable high-speed XCorr engine for high-resolution tandem mass spectrometry (2015)
    Oxford University Press
    Details
    Publication Date: 2015-12-10
    Description: : Peptide identification is an important problem in proteomics. One of the most popular scoring schemes for peptide identification is X Corr (cross-correlation). Since calculating X Corr is computationally intensive, a lot of efforts have been made to develop fast X Corr engines. However, the existing X Corr engines are not suitable for high-resolution MS/MS spectrometry because they are either slow or require a specific type of CPU. We present a portable high-speed X Corr engine for high-resolution tandem mass spectrometry by developing a novel algorithm for calculating X Corr . The algorithm enables X Corr calculation 1.25–49 times faster than previous algorithms for 0.01 Da fragment tolerance. Furthermore, our engine is easily portable to any machine with different types of CPU because it is developed in C language. Hence, our X Corr engine will expedite peptide identification by high-resolution tandem mass spectrometry. Availability and implementation: Available at http://isa.hanyang.ac.kr/HiXCorr/HiXCorr.html . Contact: hjpark@hanyang.ac.kr Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 8
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    FX: an RNA-Seq analysis tool on the cloud (2012)
    Oxford University Press
    Details
    Publication Date: 2012-03-01
    Description: : FX is an RNA-Seq analysis tool, which runs in parallel on cloud computing infrastructure, for the estimation of gene expression levels and genomic variant calling. In the mapping of short RNA-Seq reads, FX uses a transcriptome-based reference primarily, generated from ~160 000 mRNA sequences from RefSeq, UCSC and Ensembl databases. This approach reduces the misalignment of reads originating from splicing junctions. Unmapped reads not aligned on known transcripts are then mapped on the human genome reference. FX allows analysis of RNA-Seq data on cloud computing infrastructures, supporting access through a user-friendly web interface. Availability: FX is freely available on the web at ( http://fx.gmi.ac.kr ), and can be installed on local Hadoop clusters. Guidance for the installation and operation of FX can be found under the ‘Documentation’ menu on the website. Contact: jeongsun@snu.ac.kr ; jongil@snu.ac.kr Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 9
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    A NAC transcription factor and SNI1 cooperatively suppress basal pathogen resistance in Arabidopsis thaliana (2012)
    Oxford University Press
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    Publication Date: 2012-10-10
    Description: Transcriptional repression of pathogen defense-related genes is essential for plant growth and development. Several proteins are known to be involved in the transcriptional regulation of plant defense responses. However, mechanisms by which expression of defense-related genes are regulated by repressor proteins are poorly characterized. Here, we describe the in planta function of CBNAC, a calmodulin-regulated NAC transcriptional repressor in Arabidopsis . A T-DNA insertional mutant ( cbnac1 ) displayed enhanced resistance to a virulent strain of the bacterial pathogen Pseudomonas syringae DC3000 ( Pst DC3000), whereas resistance was reduced in transgenic CBNAC overexpression lines. The observed changes in disease resistance were correlated with alterations in pathogenesis-related protein 1 ( PR1 ) gene expression. CBNAC bound directly to the PR1 promoter. SNI1 ( suppressor of nonexpressor of PR genes1, inducible 1 ) was identified as a CBNAC-binding protein. Basal resistance to Pst DC3000 and derepression of PR1 expression was greater in the cbnac1 sni1 double mutant than in either cbnac1 or sni1 mutants. SNI1 enhanced binding of CBNAC to its cognate PR1 promoter element. CBNAC and SNI1 are hypothesized to work as repressor proteins in the cooperative suppression of plant basal defense.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 10
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    Neuropathogenic role of adenylate kinase-1 in A{beta}-mediated tau phosphorylation via AMPK and GSK3{beta} (2012)
    Oxford University Press
    Details
    Publication Date: 2012-05-25
    Description: Abnormally hyperphosphorylated tau is often caused by tau kinases, such as GSK3β and Cdk5. Such occurrence leads to neurofibrillary tangle formation and neuronal degeneration in tauopathy, including Alzheimer's disease (AD). However, little is known about the signaling cascade underlying the pathologic phosphorylation of tau by Aβ 42 . In this study, we show that adenylate kinase 1 (AK1) is a novel regulator of abnormal tau phosphorylation. AK1 expression is markedly increased in the brains of AD patients and AD model mice and is significantly induced by Aβ 42 in the primary neurons. Ectopic expression of AK1 alone augments the pathologic phosphorylation of tau at PHF1, CP13 and AT180 epitopes and enhances the formation of tau aggregates. Inversely, downregulation of AK1 alleviates Aβ 42 -induced hyperphosphorylation of tau. AK1 plays a role in Aβ 42 -induced impairment of AMPK activity and GSK3β activation in the primary neurons. Pharmacologic studies show that treatment with an AMPK inhibitor activates GSK3β, and a GSK3β inhibitor attenuates AK1-mediated tau phosphorylation. In a Drosophila model of human tauopathy, the retinal expression of human AK1 severely exacerbates rough eye phenotype and increases abnormal tau phosphorylation. Further, neural expression of AK1 reduces the lifespan of tau transgenic files. Taken together, these observations indicate that the neuronal expression of AK1 is induced by Aβ 42 to increase abnormal tau phosphorylation via AMPK-GSK3β and contributes to tau-mediated neurodegeneration, providing a new upstream modulator of GSK3β in the pathologic phosphorylation of tau.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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