480 research outputs found

    A mitotic kinase scaffold depleted in testicular seminomas impacts spindle orientation in germ line stem cells.

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    Correct orientation of the mitotic spindle in stem cells underlies organogenesis. Spindle abnormalities correlate with cancer progression in germ line-derived tumors. We discover a macromolecular complex between the scaffolding protein Gravin/AKAP12 and the mitotic kinases, Aurora A and Plk1, that is down regulated in human seminoma. Depletion of Gravin correlates with an increased mitotic index and disorganization of seminiferous tubules. Biochemical, super-resolution imaging, and enzymology approaches establish that this Gravin scaffold accumulates at the mother spindle pole during metaphase. Manipulating elements of the Gravin-Aurora A-Plk1 axis prompts mitotic delay and prevents appropriate assembly of astral microtubules to promote spindle misorientation. These pathological responses are conserved in seminiferous tubules from Gravin(-/-) mice where an overabundance of Oct3/4 positive germ line stem cells displays randomized orientation of mitotic spindles. Thus, we propose that Gravin-mediated recruitment of Aurora A and Plk1 to the mother (oldest) spindle pole contributes to the fidelity of symmetric cell division

    Developing a Plan for a More Diverse, Inclusive, and Equitable Library at a Research 1 Land-Grant University

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    Using the Virginia Tech strategic plan as a guide, a team of its University Libraries faculty and staff designed a strategic planning approach for the library that directly engaged with University goals and explored two areas: 1) contributing to the equity-, diversity-, and inclusion-related (EDI) goals laid out in the University strategic plan, and 2) expanding upon efforts to broaden diversity and representation in the library. The team identified four major themes: accessibility, climate, employment and professional development, outreach, and advocacy, and used these themes to develop specific recommendations. The process served to shine the light on these topics within the library, allowing for reflection and self-understanding, crucial components to change and grow with more attention to inclusion and diversity. Recognizing a need for change, it is hoped the report leads to better advocacy and ally-ship and brings issues to light for other libraries engaging in similar processes

    Commercial Fertilizers in 1946-47.

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    41 p

    Fertilizer Statistics for Texas, 1926-1938.

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    23 p

    Commercial Fertilizers in 1944-45.

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    31 p

    Commercial Fertilizers in 1945-46.

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    31 p

    Commercial Fertilizers in 1943-44.

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    pg 2

    Early-stage development of novel cyclodextrin-siRNA nanocomplexes allows for successful postnebulization transfection of bronchial epithelial cells.

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    BACKGROUND: Successful delivery of small interfering RNA (siRNA) to the lungs remains hampered by poor intracellular delivery, vector-mediated cytotoxicity, and an inability to withstand nebulization. Recently, a novel cyclodextrin (CD), SC12CDClickpropylamine, consisting of distinct lipophilic and cationic subunits, has been shown to transfect a number of cell types. However, the suitability of this vector for pulmonary siRNA delivery has not been assessed to date. To address this, a series of high-content analysis (HCA) and postnebulization assays were devised to determine the potential for CD-siRNA delivery to the lungs. METHODS: SC12CDClickpropylamine-siRNA mass ratios (MRs) were examined for size and zeta potential. In-depth analysis of nanocomplex uptake and toxicity in Calu-3 bronchial epithelial cells was examined using IN Cell(®) HCA assays. Nebulized SC12CDClickpropylamine nanocomplexes were assessed for volumetric median diameter (VMD) and fine particle fraction (FPF) and compared with saline controls. Finally, postnebulization stability was determined by comparing luciferase knockdown elicited by SC12CDClickpropylamine nanocomplexes before and after nebulization. RESULTS: SC12CDClickpropylamine-siRNA complexation formed cationic nanocomplexes of ≤200 nm in size depending on the medium and led to significantly higher levels of siRNA associated with Calu-3 cells compared with RNAiFect-siRNA-treated cells at all MRs (p CONCLUSIONS: SC12CDClickpropylamine nanocomplexes can be effectively nebulized for pulmonary delivery of siRNA using Aeroneb technology to mediate knockdown in airway cells. To the best of our knowledge, this is the first study examining the suitability of SC12CDClickpropylamine-siRNA nanocomplexes for pulmonary delivery. Furthermore, this work provides an integrated nanomedicine-device combination for future in vitro and in vivo preclinical and clinical studies of inhaled siRNA therapeutics
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