44 research outputs found

    Computational Study of Rh-Catalyzed Carboacylation of Olefins: Ligand-Promoted Rhodacycle Isomerization Enables Regioselective C–C Bond Functionalization of Benzocyclobutenones

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    The mechanism, reactivity, regio- and enantioselectivity of the Rh-catalyzed carboacylation of benzocyclobutenones are investigated using density functional theory (DFT) calculations. The calculations indicate that the selective activation of the relatively unreactive C1–C2 bond in benzocyclobutenone is achieved via initial C1–C8 bond oxidative addition, followed by rhodacycle isomerization via decarbonylation and CO insertion. Analysis of different ligand steric parameters, ligand steric contour maps, and the computed activation barriers revealed the origin of the positive correlation between ligand bite angle and reactivity. The increase of reactivity with bulkier ligands is attributed to the release of ligand–substrate repulsions in the P–Rh–P plane during the rate-determining CO insertion step. The enantioselectivity in reactions with the (<i>R</i>)-SEGPHOS ligand is controlled by the steric repulsion between the C8 methylene group in the substrate and the equatorial phenyl group on the chiral ligand in the olefin migratory insertion step

    A Neuronal Culture System to Detect Prion Synaptotoxicity

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    <div><p>Synaptic pathology is an early feature of prion as well as other neurodegenerative diseases. Although the self-templating process by which prions propagate is well established, the mechanisms by which prions cause synaptotoxicity are poorly understood, due largely to the absence of experimentally tractable cell culture models. Here, we report that exposure of cultured hippocampal neurons to PrP<sup>Sc</sup>, the infectious isoform of the prion protein, results in rapid retraction of dendritic spines. This effect is entirely dependent on expression of the cellular prion protein, PrP<sup>C</sup>, by target neurons, and on the presence of a nine-amino acid, polybasic region at the N-terminus of the PrP<sup>C</sup> molecule. Both protease-resistant and protease-sensitive forms of PrP<sup>Sc</sup> cause dendritic loss. This system provides new insights into the mechanisms responsible for prion neurotoxicity, and it provides a platform for characterizing different pathogenic forms of PrP<sup>Sc</sup> and testing potential therapeutic agents.</p></div

    sj-docx-1-pib-10.1177_09544054231201919 – Supplemental material for Fabrication of Ni-TiN nanocomposite coatings by ultrasonic assisted jet electrodeposition

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    Supplemental material, sj-docx-1-pib-10.1177_09544054231201919 for Fabrication of Ni-TiN nanocomposite coatings by ultrasonic assisted jet electrodeposition by Yuanlong Chen, Huigui Li, Jiachen Zhu, Cheng Fang, Zhongquan Li and Wei Jiang in Proceedings of the Institution of Mechanical Engineers, Part B: Journal of Engineering Manufacture</p

    The N-terminal domain of PrP<sup>C</sup> is essential for PrP<sup>Sc</sup>-induced dendritic spine loss.

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    <p>Hippocampal neurons from Tg(Δ23–111) mice (<b>A-D</b>) and Tg(Δ23–31) mice (<b>E-H</b>) (both on the <i>Prn-p</i><sup>0/0</sup> background) were treated for 24 hr with 4.4 μg/ml of PrP<sup>Sc</sup> purified without proteases (<b>B, F</b>), or with an equivalent amount of mock-purified material from uninfected brains (<b>A, E</b>). Neurons were then fixed and stained with Alexa 488-phalloidin. Scale bar in panel F = 20 μm (applicable to panels A, B, E). Pooled measurements of spine number (<b>C, G</b>) and area (<b>D, H</b>) were collected from 20–24 cells from 4 independent experiments. N.S., not significantly different by Student’s t-test.</p

    PK-digested PrP<sup>Sc</sup> causes dendritic spine loss.

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    <p>(<b>A</b>) Silver stain and Western blot (using anti-PrP antibody D18) of a PrP<sup>Sc</sup> sample and a mock-purified control sample, after digestion with PK. Lane M, molecular size markers in kDa. Hippocampal neurons from wild-type (WT) mice (<b>B, C</b>) and PrP knockout (<i>Prn-p</i><sup>0/0</sup>) mice (<b>D, E</b>) were treated for 24 hr with 4.4 μg/ml of purified, PK-treated PrP<sup>Sc</sup> (<b>C, E</b>), or with an equivalent amount of mock-purified sample (<b>B, D</b>). Neurons were then fixed and stained with Alexa 488-phalloidin. Scale bar in panel E = 20 μm (applicable to panels B-D). Pooled measurements of spine number (<b>F</b>) and area (<b>G</b>) were collected from 20–24 cells from 3 independent experiments. ***p<0.001 by Student’s t-test; N.S., not significantly different.</p

    Purified PrP<sup>Sc</sup>, prepared using pronase E, causes PrP<sup>C</sup>-dependent spine loss.

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    <p>(<b>A</b>) Silver stain and Western blot analysis (using anti-PrP antibody IPC1) of PrP<sup>Sc</sup> purified from scrapie-infected brains using pronase E, and mock-purified material from uninfected brains. Lane M, molecular size markers in kDa. Hippocampal neurons from wild-type (WT) mice (<b>B, C</b>) and PrP knockout (<i>Prn-p</i><sup>0/0</sup>) mice (<b>D, E</b>) were treated for 24 hr with 4.4 μg/ml of purified PrP<sup>Sc</sup> (<b>C, E</b>), or with an equivalent amount of material mock-purified from uninfected brains (<b>B, D</b>). Neurons were then fixed and stained with Alexa 488-phalloidin. Scale bar in panel E = 20 μm (applicable to panels B-D). Pooled measurements of spine number (<b>F</b>) and area (<b>G</b>) were collected from 16–18 cells from 3 independent experiments. ***p<0.001 or *p<0.05 by Student’s t-test; N.S., not significantly different.</p

    Purified PrP<sup>Sc</sup>, prepared without proteases, causes PrP<sup>C</sup>-dependent spine loss.

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    <p>(<b>A</b>) Silver stain and Western blot analysis (using anti-PrP antibody D18) of PrP<sup>Sc</sup> purified from scrapie-infected brains without proteases, and mock-purified material from uninfected brains. Lane M, molecular size markers in kDa. Hippocampal neurons from wild-type (WT) mice (<b>B, C</b>) and PrP knockout (<i>Prn-p</i><sup>0/0</sup>) mice (<b>D, E</b>) were treated for 24 hr with 4.4 μg/ml of purified PrP<sup>Sc</sup> (<b>C, E</b>), or with an equivalent amount of material mock-purified from uninfected brains (<b>B, D</b>). Neurons were then fixed and stained with Alexa 488-phalloidin. Scale bar in panel E = 20 μm (applicable to panels B-D). Pooled measurements of spine number (<b>F</b>) and area (<b>G</b>) were collected from 22–25 cells from 4 independent experiments. ***p<0.001 by Student’s t-test; N.S., not significantly different.</p

    ALDH<sup>high</sup>-CD8+ T treatment prolongs the overall survival of the tumor-bearing mice.

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    <p>The mice treated with ALDH<sup>high</sup>-CD8+ T cells survived much longer than the mice treated with PBS, H-CD8+ T, or ALDH<sup>low</sup>-CD8+ T cells.</p

    The identification of ALDH<sup>high</sup> cells from the human non-small cell lung cancer cells and primary tumor cells.

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    <p>ALDEFLUOR was used as a single marker to identify the ALDH<sup>high</sup> cells from the H460 cell line (A) and freshly harvested tumor cells (B). Tumor cells incubated with both ALDH and DEAB were used as a negative control.</p

    ALDH<sup>high</sup>-CD8+ T treatment inhibits subcutaneous tumor growth.

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    <p>(A) The treatment scheme. (B) The tumor sizes of the mice treated with ALDH<sup>high</sup>-CD8+ T cells were much smaller than the tumors of mice treated with PBS, H-CD8+ T, or ALDH<sup>low</sup>-CD8+ T cells.</p
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