18 research outputs found

    The <i>Drosophila</i> Toll→Dorsal/Dif and mammalian Interleukin Receptor→NFκB innate immunity pathways.

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    <p>Diagram of the <i>Tl</i>→NFκB signaling pathways in <i>Drosophila</i> and mammals. See text for details.</p

    Aβ42 induced rough eye phenotype is sensitive to <i>Toll</i> activity.

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    <p>WT: Wild type flies. Aβ: pGMR-Aβ42 transgenic flies. In the experiments shown in this figure, the flies are hemizygous for the pGMR-Aβ42 transgene. Panel A: WT: eye of a wild type fly. Aβ/+: eye of a wild type fly hemizygous for the pGMR-Aβ42 transgene. Panels B through F show sibling pGMR-Aβ42 transgene flies that are either wild type <i>Tl</i> or heterozygous for the indicated <i>Tl</i> allele. Panel B: Aβ/+: hemizygous for the Aβ transgene; Aβ/<i>Tl<sup>r4</sup></i>: heterozygous for the LOF allele <i>Tl<sup>r4</sup></i>. Panel C: Aβ/+: hemizygous for the Aβ transgene; Aβ/<i>Tl<sup>r3</sup></i>: heterozygous for the LOF allele <i>Tl<sup>r4</sup></i>. Panel D: Aβ/+: hemizygous for the Aβ transgene; Aβ/<i>Tl<sup>KG</sup></i>: heterozygous for the LOF allele <i>Tl<sup> KG03609</sup></i>. Panel E: Aβ/+: hemizygous for the Aβ transgene; Aβ/<i>Tl<sup>rk</sup></i>: heterozygous for the LOF allele <i>Tl<sup> rK343</sup></i>. Panel F: Aβ/+: hemizygous for the Aβ transgene; Aβ/<i>Tl<sup>3</sup></i>: heterozygous for the GOF allele <i>Tl<sup> r3</sup></i>.</p

    Dorsal mediates Aβ42 dependent neurodegeneration of the eye.

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    <p>Panels A–E: In the experiments shown in this figure all flies are siblings that are homozygous for the pGMR-Aβ42 transgene. The fly on the left side of each panel is a wild type sib, while the fly on the right side of each panel is a sib that is either heterozygous or homozygous for the indicated <i>dl</i> mutation. Panel A: <i>dl<sup>1</sup></i>/+. Panel B: <i>dl<sup>4</sup></i>/+ Panel C: <i>dl<sup>8</sup></i>/+ Panel D: <i>dl<sup>1</sup></i>/<i>dl<sup>1</sup></i>. Panel E: <i>dl<sup>4</sup>/dl<sup>4</sup></i>. Panel F: In this experiment both flies are hemizygous for the pGMR-Aβ42 transgene. The fly on the left is wild type, while the fly on the right is homozygous <i>dl<sup> `</sup></i>. Arrows in panels A and E point to ommatidia with dead or dying cells.</p

    Effect of mutations in the <i>Tl→ΝFκB</i> pathway on the Aβ42 induced rough eye phenotype.

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    <p>The rough eye phenotype of pGMR-Aβ42 flies was assigned a value of ++++. According to this scoring system, strong, moderate and weak suppression corresponded to +, ++, and +++. Weak and moderate enhancement corresponded to +++++ and ++++++. All flies are hemizygous for the transgene and either wild type (+) or heterozygous for the indicated mutation.</p

    Components of the <i>Toll-NF</i>κ<i>B</i> signaling pathway modulate Aβ42 polypetide induced neurodegeneration.

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    <p>Panels A–F: In the experiments shown in this figure all flies are siblings that are hemizygous for the pGMR-Aβ42 transgene. The fly on the left side of each panel is a wild type sib, while the fly on the right side of each panel is a sib that is heterozygous for the indicated mutation in the <i>Toll-NF</i>κ<i>B</i> signaling pathway mutant. Panel A: <i>dl<sup>1</sup></i>. Panel B: <i>dl<sup>4</sup></i>. Panel C: <i>dl<sup>8</sup></i>. Panel D: <i>pll<sup>2</sup></i>. Panel E: <i>pll<sup>7</sup></i>. Panel F: <i>tub</i>.</p

    Top age at onset (AAO) meta-analysis results for the <i>FOXO1</i> region.

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    1<p>Position for genome build 36.3 (hg18).</p>2<p>Required p-value level for significance p-values = 8.68E-5; <b>bold</b> indicates significant p-value.</p>3<p>Direction of effects are listed in the following order: PROGENI/GenePD, NIA Phase I, NIA Phase II, LEAPS, HIHG, NGRC; a question mark (?) indicates that the marker failed imputation (Rsq<0.30).</p>4<p>Values for imputed (I) or genotyped (G) status.</p>5<p>The meta-analysis included the PROGENI/GenePD, NIA Phase I, NIA Phase II, HIHG, and NGRC studies.</p>6<p>The SNPExpress database <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002794#pgen.1002794-Heinzen1" target="_blank">[29]</a> was used to look up eSNP relationships between the expression of <i>FOXO1</i> transcripts or exons and the SNPs of interest. The best <i>FOXO1</i> eSNP result is displayed if a p-value<0.05 was observed. The presented eSNP results were obtained in brain tissue. N/A values are used when the SNPs were not available in the database.</p

    Description of retained brain samples for the Agilent microarray study.

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    1<p>PMI: post-mortem interval.</p>2<p>RIN: RNA Integrity Number.</p>3<p>The pH was measured following a previously established protocol <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002794#pgen.1002794-Harrison1" target="_blank">[58]</a>.</p

    Expression by genotype relationship between the <i>SMOX</i> probe, A_23_P102731, and the <i>GAK</i> SNP, rs11731387.

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    <p>The box whiskers extend to the most extreme data point, which is at most 1.5 times the interquartile range from the box. The result for the 2-degree of freedom test was p = 8.1E-6, and the eSNP relationship was stronger in PD (p = 7.47E-5, beta = −0.727) than in controls (p = 0.037, beta = −0.494). The minor allele frequency for rs11731387 in the used brain sample was 0.15, and the odds ratio for this SNP in the additive model affection study of the meta-GWAS was 1.35.</p

    FoxO1 TFBS genes with evidence of partial mediation for the relationship between <i>FOXO1</i> and PD.

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    1<p>The direct effect represents the effect of <i>FOXO1</i> expression on PD directly, while the indirect effect represents the effect that is mediated through each FoxO1 TFBS gene.</p

    Top microarray probes.

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    <p>Probes with FDR-adjusted p-values smaller than 0.05 and with expression differences between PD and control prefrontal cortex BA9 samples greater than 1.5 fold changes. Twenty-one probes (42%) were in genes with FoxO1 transcription factor binding sites. The GENE-E software (<a href="http://www.broadinstitute.org/cancer/software/GENE-E/" target="_blank">http://www.broadinstitute.org/cancer/software/GENE-E/</a>) was used to generate the heatmap.</p
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