15 research outputs found

    International evidence on inflation expectations during Sustained Off-Target Inflation episodes

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    The high level of UK inflation in recent years raises the possibility that inflation expectations may drift upwards, making the period of above-target inflation last for longer. This article presents some evidence on inflation expectations during Sustained Off-Target Inflation (SOTI) episodes in other inflation-targeting countries and outlines some of the key trends. The evidence suggests that short and medium-term inflation expectations have tended to drift in the direction of the deviation of inflation from target. But generally the movements in inflation expectations were more gradual than movements in inflation itself and expectations returned to their previous level once inflation returned to target.

    GLUTATHIONE S

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    Glutathione Stransferase omega 1 and omega 2 pharmacogenomics. Drug Metab Dispos

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    ABSTRACT Glutathione S-transferase omega 1 and omega 2 (GSTO1 and GSTO2) catalyze monomethyl arsenate reduction, the rate-limiting reaction in arsenic biotransformation. As a step toward pharmacogenomic studies of these phase II enzymes, we resequenced human GSTO1 and GSTO2 using DNA samples from four ethnic groups. We identified 31 and 66 polymorphisms in GSTO1 and GSTO2, respectively, with 4 nonsynonymous coding single nucleotide polymorphisms (cSNPs) in each gene. There were striking variations among ethnic groups in polymorphism frequencies and types. Expression constructs were created for all eight nonsynonymous cSNPs as well as a deletion of codon 155 in GSTO1, and those constructs were used to transfect COS-1 cells. Quantitative Western blot analysis, after correction for transfection efficiency, showed a reduction in protein level of greater than 50% for the GSTO1 Tyr32 variant allozyme when compared with wild type (WT), while levels for the Asp140, Lys208, Val236 and codon 155 deletion variant constructs were similar to that of the WT. For GSTO2, the Tyr130 and Ile158 variant allozymes showed 50% and 84% reductions in levels of expression, respectively, when compared to WT, while the Ile41 and Asp142 allozymes displayed levels similar to that of WT GSTO2. Rabbit reticulocyte lysate (RRL) degradation studies showed that the GSTO1 Tyr32 and the GSTO2 Tyr130, Ile158 and Asp142/Ile158 variant allozymes were degraded more rapidly than were their respective WT allozymes. These observations raise the possibility of functionally significant pharmacogenomic variation in the expression and function of GSTO1 and GSTO2

    Gene Expression, Single Nucleotide Variant and Fusion Transcript Discovery in Archival Material from Breast Tumors

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    <div><p>Advantages of RNA-Seq over array based platforms are quantitative gene expression and discovery of expressed single nucleotide variants (eSNVs) and fusion transcripts from a single platform, but the sensitivity for each of these characteristics is unknown. We measured gene expression in a set of manually degraded RNAs, nine pairs of matched fresh-frozen, and FFPE RNA isolated from breast tumor with the hybridization based, NanoString nCounter (226 gene panel) and with whole transcriptome RNA-Seq using RiboZeroGold ScriptSeq V2 library preparation kits. We performed correlation analyses of gene expression between samples and across platforms. We then specifically assessed whole transcriptome expression of lincRNA and discovery of eSNVs and fusion transcripts in the FFPE RNA-Seq data. For gene expression in the manually degraded samples, we observed Pearson correlations of >0.94 and >0.80 with NanoString and ScriptSeq protocols, respectively. Gene expression data for matched fresh-frozen and FFPE samples yielded mean Pearson correlations of 0.874 and 0.783 for NanoString (226 genes) and ScriptSeq whole transcriptome protocols respectively, p<2x10<sup>-16</sup>. Specifically for lincRNAs, we observed superb Pearson correlation (0.988) between matched fresh-frozen and FFPE pairs. FFPE samples across NanoString and RNA-Seq platforms gave a mean Pearson correlation of 0.838. In FFPE libraries, we detected 53.4% of high confidence SNVs and 24% of high confidence fusion transcripts. Sensitivity of fusion transcript detection was not overcome by an increase in depth of sequencing up to 3-fold (increase from ~56 to ~159 million reads). Both NanoString and ScriptSeq RNA-Seq technologies yield reliable gene expression data for degraded and FFPE material. The high degree of correlation between NanoString and RNA-Seq platforms suggests discovery based whole transcriptome studies from FFPE material will produce reliable expression data. The RiboZeroGold ScriptSeq protocol performed particularly well for lincRNA expression from FFPE libraries, but detection of eSNV and fusion transcripts was less sensitive.</p> </div

    Technical Replicates and Cross-Platform Correlations.

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    <p>Log<sub>2</sub> gene expression for FFPE technical replicate with (A) NanoString platform and (B) RiboZeroGold ScriptSeq; (C) Gene expression correlation of nine FFPE samples across nanoString and RiboZeroGold ScriptSeq protocols. Gene expression correlation of nine fresh-frozen (FROZ) RNA samples across (D) nanoString and ScriptSeq, (E) nanoString and TruSeq and (F) RiboZeroGold ScriptSeq and TruSeq.</p

    RNA-Seq Mapped Reads, Fusion and eSNV statistics By Protocol.

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    <p>(A) % reads mapped to genome, genes and exon junctions, B) Venn diagram of fusion transcript detection, (C) Number SNV calls, (D) Correlation of FFPE library insert size with sensitivity for single nucleotide variant detection.</p

    Gene Expression correlations with Nanostring, ScriptSeq And TruSeq platforms.

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    <p>Nanostring correlation for (A) undegraded RNA against the same manually degraded sample (RIN=2.0); (B) log<sub>2</sub> fold change between two high quality RNAs and the same two samples when manually degraded (RIN 2.0); (C) nine matched fresh-frozen and FFPE pairs. ScriptSeq correlation for (D) undegraded RNA against the same manually degraded sample (RIN=2.0); (E) log<sub>2</sub> fold change between two high quality RNAs and the same two samples when manually degraded (RIN 2.0); (F) nine matched fresh-frozen and FFPE pairs.</p
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