39 research outputs found

    Release of Intracellular Calcium Stores Facilitates Coxsackievirus Entry into Polarized Endothelial Cells

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    Group B coxsackieviruses (CVB) are associated with viral-induced heart disease and are among the leading causes of aseptic meningitis worldwide. Here we show that CVB entry into polarized brain microvasculature and aortic endothelial cells triggers a depletion of intracellular calcium stores initiated through viral attachment to the apical attachment factor decay-accelerating factor. Calcium release was dependent upon a signaling cascade that required the activity of the Src family of tyrosine kinases, phospholipase C, and the inositol 1,4,5-trisphosphate receptor isoform 3. CVB-mediated calcium release was required for the activation of calpain-2, a calcium-dependent cysteine protease, which controlled the vesicular trafficking of internalized CVB particles. These data point to a specific role for calcium signaling in CVB entry into polarized endothelial monolayers and highlight the unique signaling mechanisms used by these viruses to cross endothelial barriers

    Consideracoes sobre servicos de advocacy para pessoas idosas no contexto de revitalizacao urbana

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    This article is based on a recently completed evaluation study of an older people’s advocacy project, The Generation Project, in the context of urban regeneration in East Manchester. East Manchester has a higher rate of older people than any other part of Manchester. Two main aspects are outlined here, first, how clients and partner organisations identify psycho-social and practical benefits from the services of the Project; and second, how processes of individual and collective advocacy created the conditions for a sense of control, while at the same time making explicit helplessness and frustration in other contexts. Issues of trust, dignity and respect were fundamental to effective relationships between older people and service providers. Further, while the small scale nature of the Project worked well for older clients, this compromised the development of strong partnerships with (more powerful) organisations. Advocacy as a gateway to empowerment required individual determination, collective effort, organisational commitment and joint working to be successful

    On the neuro-muscular control of trochlean joints.

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    This paper presents a simplified dynamical model for the control of one-degree-of-freedom synovial joints considered as pure trochlean joints. This model considers the joint dynamics, the dynamics of the corresponding muscles and their calcium balance dynamics, as well as position and force feedbacks provided by the spindles and the Golgi tendon organs. Delays in the transmission of information are also taken into account as they proved to be of critical importance for the dynamical behavior of the considered systems. The linearized version of this model, which is valid for a rather wide range of movements, also allows us to investigate the stability of the system, as well as its stability robustness with respect to the feedback gains. Further, particular behaviors such as tremor are described

    Consideracoes sobre services de advocacy para pessoas idosas no contexto de revitalizacao urbana. (Advocacy services for older people in urban regeneration contexts)

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    This article is based on an evaluation study of an older people's advocacy project, the Gateway Project, in the context of urban regeneration in East Manchester.East Manchester has a higher proportin of older people than any other part of Manchester. Two main aspects are outlined here, first, how clients and partners identify psych-social and practical benefits from the Project's services; and second, how processes of individual and collective advocacy created the conditions for a sense of control, while at the same time making explicit helplessness and frustration in other contexts. Issues of trust, dignity and respect were fundamental to effective relationships between older people and service providers. Further, while the small scale nature of the Project worked well for older clients, this compromised the development of strong partnerships with (more powerful)organisations. Advocacy as a gateway to empowerment required individual determination, collective effort, organisational commitment and joint working to be successful

    Effect of ouabain on membrane conductances and volume in A6 cells.

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    The present study reports the effect of a reduction in the Na(+)-transport rate on cell volume. A decrease in transport rate was achieved by inhibition of the basolateral Na+/K+ pump with ouabain. Cultured A6 cell monolayers were short-circuited and exposed to ouabain at the basolateral surface. In one series of experiments, cells were impaled with microelectrodes to measure cell voltage, apical fractional resistance and thus derive membrane conductances. Another set, A6, served for cell height measurements. Ouabain decreased short-circuit current (Isc), which is an index of transepithelial Na+ transport: the reduction in transport rate varied from 26 to 79% within 10 min. Equivalent circuit analysis revealed a 20% decrease in apical membrane conductance (ga), whereas basolateral membrane conductance (gb) increased by 66%. A decrease in cell voltage (12 mV) together with drop in ga during ouabain may account for the reduction in Isc. The rise in gb is mainly due to a gain in Cl- conductance which increased from 114 to 613 microS/cm2, compatible with activation of Cl- channels. All of this occurs without a detectable change in cell height. We may conclude from these data that inhibition of Na+ exit by ouabain is quickly compensated by a decrease in apical Na+ entry and an increase in basolateral Cl- conductance. Constant cell volume during ouabain implies that the total cell solute is essentially unchanged

    Missing data imputation in clinical studies - ignorable missingness and sensitivity analysis

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