14 research outputs found

    Each dog’s performance discriminating between baseline and stress samples NB.

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    Each dog’s performance discriminating between baseline and stress samples NB.</p

    Odour control data for each dog.

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    Odour control data for each dog.</p

    Diagram illustrating the general two phase, three alternative forced-choice procedure.

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    Each cylinder represents a port as shown in Fig 1.</p

    Diagram illustrating the within-subject test design, where the target = stress sample (Person A immediately after MAT), distractor = baseline sample (Person A, four minutes before, at baseline), blank = unused gauze in a glass vial.

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    Diagram illustrating the within-subject test design, where the target = stress sample (Person A immediately after MAT), distractor = baseline sample (Person A, four minutes before, at baseline), blank = unused gauze in a glass vial.</p

    Fig 2 -

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    A) A single arm of the apparatus with an open port holding a sample. B) A single arm of the apparatus with the port secured by a lid.</p

    Each dog performing their alert behaviour to indicate their choice on the three alternative forced choice apparatus.

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    Top Left: Soot (stand-stare), Top Right: Fingal (stand-stare), Bottom Left: Winnie (nose-on sit), Bottom Right: Treo (nose-on sit).</p

    Timeline of the data collection process for the in-person protocol.

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    Yellow highlight shows physiological data used for assessment of stress. Green highlight shows self-report stress data. Blue highlight shows sweat/breath samples that would be later shown to a dog if the participant met the criteria of stress.</p

    mTOR-Dependent and Independent Survival Signaling by PI3K in B Lymphocytes

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    <div><p>Peripheral B lymphocyte survival requires the B cell receptor (BCR) and B cell activating factor (BAFF) binding to its receptor (BAFF-R). Deletion of the BCR, or its signal transducing chaperone Igβ, leads to rapid loss of mature B cells, indicating that signals initiated at the BCR are crucial for B cell survival. BAFF or BAFF-R deficiency also significantly reduces the numbers of mature B cells despite normal BCR expression. Together, these observations indicate that continued BCR and BAFF-R signaling are essential for the survival of mature resting B cells in the periphery. Here we demonstrate that tonic BCR signals up-regulate p100 (Nfkb2) as well as Mcl-1 protein expression at a post-transcriptional level via a PI3K-dependent pathway. p100 expression is mTOR-independent, whereas Mcl-1 expression is mTOR-dependent. BAFF treatment further elevated Mcl-1 levels by an mTOR-independent pathway, while consuming p100. Accordingly, Mcl-1 induction by BAFF is abrogated in <i>Nfkb2</i><sup><i>-/-</i></sup> B cells. We propose that the cumulative effects of the BCR and BAFF-R signaling pathways increase Mcl-1 levels beyond the threshold required for B cell survival.</p></div

    Signaling pathway to BCR-induced p100 expression.

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    <p>(A-C) CD43<sup>-</sup> splenic B cells from Bim<sup>-/-</sup> mice were treated with anti-IgM F(ab’)<sub>2</sub> (15μg/ml) for various times in the presence or absence of Syk kinase inhibitor R406 (4μM), Bruton’s tyrosine kinase inhibitor Ibrutinib (PCI-32765) (20nM), or TORC1 inhibitor rapamycin (50nM). Whole cell extracts were fractionated by SDS-PAGE and p100 proteins were analyzed by immunoblotting. β-actin was used as a loading control to normalize between samples. (D, E) CD43<sup>-</sup> splenic B cells from BL6, BCAP<sup>-/-</sup> (D) or CD19<sup>-/-</sup> (E) mice were cultured for the indicated times with or without anti-IgM F(ab’)<sub>2</sub> (15μg/ml). Whole cell extracts were prepared and assayed for p100 protein levels by Western blot analysis. β-actin was used as a loading control to normalize between samples. Representative gels from 3 independent experiments are shown. Cell viability is provided in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0146955#pone.0146955.s004" target="_blank">S4 Fig</a>.</p
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