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Incoming Simian Virus 40 particles bind to their cellular receptor, the glycolipid GM1, in the plasma membrane and thereby induce membrane deformation beneath the virion leading to endocytosis and infection. Efficient membrane deformation depends on receptor lipid structure and the organization of binding sites on the internalizing particle. To determine the role of receptor diffusion, concentration and the number of receptors required for stable binding in this interaction, we analyze the binding of SV40 to GM1 in supported membrane bilayers by computational modeling based on experimental data. We measure the diffusion rates of SV40 virions in solution by fluorescence correlation spectroscopy and of the receptor in bilayers by single molecule tracking. Quartz-crystal microbalance with dissipation (QCM-D) is used to measure binding of SV40 virus-like particles to bilayers containing the viral receptor GM1. We develop a phenomenological stochastic dynamics model calibrated against this data, and use it to investigate the early events of virus attachment to lipid membranes. Our results indicate that SV40 requires at least 4 attached receptors to achieve stable binding. We moreover find that receptor diffusion is essential for the establishment of stable binding over the physiological range of receptor concentrations and that receptor concentration controls the mode of viral motion on the target membrane. Our results provide quantitative insight into the initial events of virus-host interaction at the nanoscopic level. © 2013 Szklarczyk et al., SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND The ability of transesophageal color Doppler echocardiography to provide high-resolution images of both cardiac structure and blood flow in real time is advantageous for many clinical purposes. This study was performed to determine the utility of the regurgitant jet width at its origin measured by transesophageal Doppler color flow imaging in the assessment of severity of mitral regurgitation. METHODS AND RESULTS Sixty-three consecutive patients with mitral regurgitation underwent transesophageal color Doppler examination, and the diameter of regurgitant jet at its origin was measured. Both right and left cardiac catheterizations were performed within 24 hours of Doppler studies, and angiographic grading of mitral regurgitation and regurgitant stroke volume were evaluated. There was a close relation between the jet diameter at its origin measured by transesophageal Doppler color flow imaging and the angiographic grade of mitral regurgitation (r = 0.86, p less than 0.001). A jet diameter of 5.5 mm or more identified severe mitral regurgitation (grade III or IV) with a sensitivity of 92%, specificity of 92%, and positive and negative predictive values of 88% and 95%, respectively. In 31 patients with isolated mitral regurgitation, the jet diameter correlated well with the regurgitant stroke volume determined by a combined hemodynamic-angiographic method (r = 0.85, p less than 0.001). A jet diameter of 5.5 mm or more identified a regurgitant stroke volume of 60 ml or more with a sensitivity of 88%, specificity of 93%, and positive and negative predictive values of 94% and 87%, respectively. CONCLUSIONS The regurgitant jet width at its origin measured by transesophageal Doppler color flow imaging provides a simple and useful method of measuring the severity of mitral regurgitation, and it may allow differentiation between mild and severe mitral regurgitation.

OBJECTIVE--To assess the usefulness of pulsed Doppler echocardiography as a method of measuring the regurgitant fraction in patients with mitral regurgitation. PATIENTS AND METHODS--Twenty controls and 27 patients with isolated mitral regurgitation underwent Doppler studies. In the patients the study was performed within 48 hours of cardiac catheterisation. Aortic outflow was measured in the centre of the aortic annulus, and mitral inflow was derived from the flow velocity at the tip of the leaflets and the area of the elliptical mitral opening. The regurgitant fraction was calculated as the difference between the two flows divided by the mtiral inflow. RESULTS--In the 20 controls the two flows were almost identical (mitral inflow, 4.44 (SD 0.88) l/min; aortic outflow, 4.58 (SD 0.84) l/min), with a mean regurgitant fraction of 4.2 (SD 8.4)%. In patients with mitral regurgitation, the mitral inflow was significantly higher than the aortic outflow (8.8 (3.6) v 4.3 (1.1) l/min). In most patients the Doppler-derived regurgitant fraction (45.8 (19.2)%) accorded closely with the regurgitant fraction (41.3 (SD 17.8)%) determined by the haemodynamic technique. CONCLUSION--Pulsed Doppler echocardiography, with an instantaneous velocity-valve area method for calculating mitral inflow, reliably measured the severity of regurgitation in patients with mitral regurgitation.

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OBJECTIVE--To study the prevalence and the characteristics of physiological valve regurgitation. DESIGN--Pulsed wave Doppler echocardiography, continuous wave Doppler echocardiography and Doppler colour flow mapping were performed prospectively in healthy volunteers. SETTING--Echocardiography laboratory in a city hospital. PATIENTS--32 consecutive healthy volunteers (age 21-49 years, mean age 29.4). MAIN OUTCOME MEASURES--Identification of regurgitation with colour Doppler flow mapping and measurement of the jet area, jet length, and maximal velocity of the regurgitation. RESULTS--Regurgitation was recorded at the pulmonary (100%), tricuspid (100%), mitral (56%), and aortic valves (6%). The velocity of pulmonary and tricuspid regurgitation was similar to that predicted from the pressure gradient calculated from the Bernoulli equation. The jet area and jet length were generally small. CONCLUSION--Trivial regurgitation from the pulmonary, tricuspid, and mitral valves is common in healthy people. It is important to take such regurgitation into account when valve disease is diagnosed.

We investigated a T-cell activation deficiency in a 3-month-old boy with protracted diarrhea, serious cytomegalovirus pneumonia, and a family history (in a brother) of cytomegalovirus infection and toxoplasmosis. In spite of detection of normal number of peripheral lymphocytes, T cells did not proliferate after activation by anti-CD3 and anti-CD2 antibodies, although proliferation induced by antigens was detectable. We sought to determine the origin of this defect as it potentially represented a valuable tool to analyze T-cell physiology. T-cell activation by anti-CD3 antibody or phytohemagglutinin (PHA) led to reduced interleukin-2 (IL-2) production and abnormal nuclear factor-activated T cell (NF-AT; a complex regulating the IL-2 gene transcription) binding activity to a specific oligonucleotide. T-cell proliferation was restored by IL-2. Early events of T-cell activation, such as anti-CD3 antibody-induced cellular protein tyrosine phosphorylation, p59fyn and p56lck kinase activities, and phosphoinositide turnover, were found to be normal. In contrast, anti-CD3 antibody-induced Ca2+ flux was grossly abnormal. Release from endoplasmic reticulum stores was detectable as tested in the presence of anti-CD3 antibody or thapsigargin after cell membrane depolarization in a K+ rich medium, whereas extracellular entry of Ca2+ was defective. The latter abnormality was not secondary to defective K+ channel function, which was found to be normal. A similar defect was found in other hematopoietic cell lineages and in fibroblasts as evaluated by both cytometry and digital video imaging experiments at a single-cell level. This primary T-cell immunodeficiency appears, thus, to be due to defective Ca2+ entry through the plasma membrane. The same abnormality did not alter B-cell proliferation, platelet function, and polymorphonuclear neutrophil (PMN) function. Elucidation of the mechanism underlying this defect would help to understand the physiology of Ca2+ mobilization in T cells.

The inspiratory muscle tension-time index TT0.1 (given by P0.1/PI-max x TI/TTOT) could be used to reliably assess inspiratory muscle activity during exercise. So far, the correlation between the TT0.1 and diaphragmatic activity has not been measured and the TT0.1 has not been compared with other measurements of the inspiratory muscle load such as the transdiaphragmatic pressure index or TTdi. In this study we hypothesize that the TT0.1 measuring the mouth is a noninvasive reflection of the electromyographic activity of the diaphragm. We simultaneously measured TT0.1 and surface EMG (SEMG) of 8 trained subjects at rest and during incremental exercise. The curvature of TT0.1 and the root mean square (RMS) follow the same trend during the incremental exercise with a significant correlation between TT0.1 and surface EMG parameters (RMS; r = 0.81 p < 0.001 and MPF; r = 0.80 p < 0.001 respectively). We conclude that TT0.1 measured as s an adequate noninvasive method reflects the diaphragmatic activity during incremental exercise in healthy subjects. \textcopyright Journal of Sports Science and Medicine (2018).