4,933 research outputs found

    Division and the Giambelli Identity

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    Given two polynomials f(x) and g(x), we extend the formula expressing the remainder in terms of the roots of these two polynomials to the case where f(x) is a Laurent polynomial. This allows us to give new expressions of a Schur function, which generalize the Giambelli identity.Comment: 9 pages, 1 figur

    Vasodilator Stimulated Phosphoprotein (VASP) Regulates Actin Polymerization and Contraction in Airway Smooth Muscle by a Vinculin-dependent Mechanism

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    Vasodilator-stimulated phosphoprotein (VASP) can catalyze actin polymerization by elongating actin filaments. The elongation mechanism involves VASP oligomerization and its binding to profilin, a G-actin chaperone. Actin polymerization is required for tension generation during the contraction of airway smooth muscle (ASM); however, the role of VASP in regulating actin dynamics in ASM is not known. We stimulated ASM cells and tissues with the contractile agonist acetylcholine (ACh) or the adenylyl cyclase activator, forskolin (FSK), a dilatory agent. ACh and FSK stimulated VASP Ser157 phosphorylation by different kinases. Inhibition of VASP Ser157 phosphorylation by expression of the mutant VASP S157A in ASM tissues suppressed VASP phosphorylation and membrane localization in response to ACh, and also inhibited contraction and actin polymerization. ACh but not FSK triggered the formation of VASP-VASP complexes as well as VASP-vinculin and VASP-profilin complexes at membrane sites. VASP-VASP complex formation and the interaction of VASP with vinculin and profilin were inhibited by expression of the inactive vinculin mutant, vinculin Y1065F, but VASP phosphorylation and membrane localization were unaffected. We conclude that VASP phosphorylation at Ser157 mediates its localization at the membrane, but that VASP Ser157 phosphorylation and membrane localization are not sufficient to activate its actin catalytic activity. The interaction of VASP with activated vinculin at membrane adhesion sites is a necessary prerequisite for VASP-mediated molecular processes necessary for actin polymerization. Our results show that VASP is a critical regulator of actin dynamics and tension generation during the contractile activation of ASM

    Teledentistry: A Systematic Review of Clinical Outcomes, Utilization and Costs

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    Purpose: The purpose of this systematic review is to identify clinical outcomes, health care utilization and costs associated with teledentistry. Relevant databases were searched for articles on teledentistry published until March 2012, reference lists examined and key journals hand searched. Of a possible 58 articles, 19 studies met the inclusion criteria. Clinical outcomes were generally improved following a teledentistry intervention and satisfaction with teledentistry was consistently high. The few studies examining health care utilization reported mixed findings, but preliminary evidence suggests cost savings for health care facilities. There is a consistent trend in the literature supporting the efficacy and effectiveness of teledentistry. Further research is needed to identify the effectiveness, efficiency, utilization and costs of teledentistry as it could provide the key to improving access to care

    A novel role for RhoA GTPase in the regulation of airway smooth muscle contraction

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    Recent studies have demonstrated a novel molecular mechanism for the regulation of airway smooth muscle (ASM) contraction by RhoA GTPase. In ASM tissues, both myosin light chain (MLC) phosphorylation and actin polymerization are required for active tension generation. RhoA inactivation dramatically suppresses agonist-induced tension development and completely inhibits agonist-induced actin polymerization, but only slightly reduces MLC phosphorylation. The inhibition of MLC phosphatase does not reverse the effects of RhoA inactivation on contraction or actin polymerization. Thus, RhoA regulates ASM contraction through its effects on actin polymerization rather than MLC phosphorylation. Contractile stimulation of ASM induces the recruitment and assembly of paxillin, vinculin, and focal adhesion kinase (FAK) into membrane adhesion complexes (adhesomes) that regulate actin polymerization by catalyzing the activation of cdc42 GTPase by the G-protein-coupled receptor kinase-interacting target (GIT) - p21-activated kinase (PAK) - PAK-interacting exchange factor (PIX) complex. Cdc42 is a necessary and specific activator of the actin filament nucleation activator, N-WASp. The recruitment and activation of paxillin, vinculin, and FAK is prevented by RhoA inactivation, thus preventing cdc42 and N-WASp activation. We conclude that RhoA regulates ASM contraction by catalyzing the assembly and activation of membrane adhesome signaling modules that regulate actin polymerization, and that the RhoA-mediated assembly of adhesome complexes is a fundamental step in the signal transduction process in response to a contractile agonist

    Design, Stability and Efficacy of a New Targeting Peptide for Nanoparticulate Drug Delivery to SH-SY5Y Neuroblastoma Cells

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    In recent years, rabies virus-derived peptide (RDP) has shown promise as a specific neural cell targeting ligand, however stability of the peptide in human serum was unknown. Herein, we report the molecular modelling and design of an optimised peptide sequence based on interactions of RDP with the α7 subunit of the nicotinic acetylcholine receptor (nAChR). The new sequence, named DAS, designed around a 5-mer sequence which demonstrated optimal nAChR binding in silico, showed greatly improved stability for up to 8 hours in human serum in comparison to RDP, which degraded within 2 hours at 37 °C. In vitro analysis using SH-SY5Y neuroblastoma cells showed that DAS-conjugated nanoparticles containing the cytotoxic drug doxorubicin (DAS-Dox-NP) displayed significantly enhanced cytotoxicity compared with untargeted doxorubicin-loaded nanoparticles (Dox-NP). DAS-Dox-NP had no significant effect on non-neural cell types, confirming its neural-specific targeting properties. In this manuscript, we report the design and testing of an optimised peptide ligand, conjugated to a nanoparticulate delivery vehicle and specifically targeted to neural cells. Future impact of an innovative targeting peptide ligand combining the ability to selectively identify the target and facilitate cellular internalisation could enable the successful treatment of many neural cell disorders

    What Roles Do Chinese Health Sciences Libraries Play in Their Nation\u27s Cigarette Smoking Public Health Crisis?

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    Objectives: Cigarette smoking remains a major cause of death in China. Are health sciences libraries in China currently providing awareness, advocacy, or research support for the societal benefits of smoking reduction? Methods: Following institutional review board approval, Library contacts for Chinese schools of medicine, public health, and pharmacy were identified. A bilingual online survey was constructed to obtain respondents’ demographic detail and answers to questions about library resources and services that constitute academic awareness, advocacy, curriculum, or research support about tobacco and smoking. Results: 43% of reporting librarians work on a smoke-free campus. 100% of all reporting libraries work in smoke-free libraries, though 6% of the reporting libraries offer a smoking room for staff. All reporting libraries contain printed material on the dangers of smoking. Student requests for materials or acquisition recommendations are infrequent. More than 60% of the librarians report medical residents occasionally ask for tobacco-related literature. Nearly 60% of librarians reported faculty occasionally ask for materials about smoking. More than 60% of instructors were reported to occasionally ask for database searches about cigarettes or tobacco. 33% of librarians reported creating a collection guide about smoking. 15% of reporting libraries hosted a traveling exhibit on smoking. Conclusion: Some Chinese health sciences libraries are providing public health information and collaborating with faculty and students to support the reduction of smoking and tobacco use. Anecdotal statements collected from survey participants confirms their awareness of the educational and advocacy roles librarians play in their country\u27s smoking crisis
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