108 research outputs found

    Geometric Sensing in Cells - a Molecular Approach

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    Patient-Centered E-Health: A Status Report

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    Patient-Centered E-Health (PCEH) is an increasingly important part of health information technology. Yet the literature in this area is mainly descriptive and atheoretical, which limits opportunities for research advancement. This paper addresses the theoretical proposition that the benefits of PCEH can be maximized by incorporating three essential characteristics: Patient-focus, patient-activity, and patient-empowerment. We conduct a literature review of e-health research published between 2007 and 2011 to assess the relevance of these characteristics to the underlying domain and their relationships to one another. The results indicate the PCEH characteristics are generalizable to the existing research literature, are generalizable across place and time, and exhibit substantial interrelationships. These findings are encouraging to further development of a predictive theory of PCEH

    Surface Optomechanics: Analytic Solution of Detection Limits of Surface Acoustic Waves in Various Fluids

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    Here we derive the absolute detection limits of various families of surface acoustic waves (SAW) resulting from Brillouin scattering in a whispering gallery resonator (WGR). Given this limit, we calculate the absolute concentration limits for detection of pollutant chemicals in air, water, or other fluids surrounding the WGR. General equations for SAW velocity, linewidth, and detectability are given

    Tropomyosin controls sarcomere-like contractions for rigidity sensing and suppressing growth on soft matrices

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    Cells test the rigidity of the extracellular matrix by applying forces to it through integrin adhesions. Recent measurements show that these forces are applied by local micrometre-scale contractions, but how contraction force is regulated by rigidity is unknown. Here we performed high temporal- and spatial-resolution tracking of contractile forces by plating cells on sub-micrometre elastomeric pillars. We found that actomyosin-based sarcomere-like contractile units (CUs) simultaneously moved opposing pillars in net steps of ∼2.5 nm, independent of rigidity. What correlated with rigidity was the number of steps taken to reach a force level that activated recruitment of α-actinin to the CUs. When we removed actomyosin restriction by depleting tropomyosin 2.1, we observed larger steps and higher forces that resulted in aberrant rigidity sensing and growth of non-transformed cells on soft matrices. Thus, we conclude that tropomyosin 2.1 acts as a suppressor of growth on soft matrices by supporting proper rigidity sensing

    Amyloid-b peptide on sialyl-LewisX-selectin-mediated membrane tether mechanics at the cerebral endothelial cell surface

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    Increased deposition of amyloid-b peptide (Ab) at the cerebral endothelial cell (CEC) surface has been implicated in enhancement of transmigration of monocytes across the brain blood barrier (BBB) in Alzheimer’s disease (AD). In this study, quantitative immunofluorescence microscopy (QIM) and atomic force microscopy (AFM) with cantilevers biofunctionalized by sialyl-Lewisx (sLex) were employed to investigate Ab-altered mechanics of membrane tethers formed by bonding between sLex and p-selectin at the CEC surface, the initial mechanical step governing the transmigration of monocytes. QIM results indicated the ability for Ab to increase p-selectin expression at the cell surface and promote actin polymerization in both bEND3 cells (immortalized mouse CECs) and human primary CECs. AFM data also showed the ability for Ab to increase cell stiffness and adhesion probability in bEND3 cells. On the contrary, Ab lowered the overall force of membrane tether formation (Fmtf), and produced a bimodal population of Fmtf, suggesting subcellular mechanical alterations in membrane tethering. The lower Fmtf population was similar to the results obtained from cells treated with an F-actin-disrupting drug, latrunculin A. Indeed, AFM results also showed that both Ab and latrunculin A decreased membrane stiffness, suggesting a lower membrane-cytoskeleton adhesion, a factor resulting in lower Fmtf. In addition, these cerebral endothelial alterations induced by Ab were abrogated by lovastatin, consistent with its anti-inflammatory effects. In sum, these results demonstrated the ability for Ab to enhance p-selectin expression at the CEC surface and induce cytoskeleton reorganization, which in turn, resulted in changes in membrane-cytoskeleton adhesion and membrane tethering, mechanical factors important in transmigration of monocytes through the BBB.This work was supported by Alzheimer Association Grant NIRG-06-24448; NIH Grant 1P01 AG18357, R21NS052385, 5R21AG032579 and in part by 1P01HL095486 and AHA 0835676N; ‘‘Bolashak’’ scholarship and Ministry of Education and Science of the Republic of Kazakhstan 1029/GF2. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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