Nano-motion Dynamics are Determined by Surface-Tethered Selectin Mechanokinetics and Bond Formation

The interaction of proteins at cellular interfaces is critical for many biological processes, from intercellular signaling to cell adhesion. For example, the selectin family of adhesion receptors plays a critical role in trafficking during inflammation and immunosurveillance. Quantitative measurements of binding rates between surface-constrained proteins elicit insight into how molecular structural details and post-translational modifications contribute to function. However, nano-scale transport effects can obfuscate measurements in experimental assays. We constructed a biophysical simulation of the motion of a rigid microsphere coated with biomolecular adhesion receptors in shearing flow undergoing thermal motion. The simulation enabled in silico investigation of the effects of kinetic force dependence, molecular deformation, grouping adhesion receptors into clusters, surface-constrained bond formation, and nano-scale vertical transport on outputs that directly map to observable motions. Simulations recreated the jerky, discrete stop-and-go motions observed in P-selectin/PSGL-1 microbead assays with physiologic ligand densities. Motion statistics tied detailed simulated motion data to experimentally reported quantities. New deductions about biomolecular function for P-selectin/PSGL-1 interactions were made. Distributing adhesive forces among P-selectin/PSGL-1 molecules closely grouped in clusters was necessary to achieve bond lifetimes observed in microbead assays. Initial, capturing bond formation effectively occurred across the entire molecular contour length. However, subsequent rebinding events were enhanced by the reduced separation distance following the initial capture. The result demonstrates that vertical transport can contribute to an enhancement in the apparent bond formation rate. A detailed analysis of in silico motions prompted the proposition of wobble autocorrelation as an indicator of two-dimensional function. Insight into two-dimensional bond formation gained from flow cell assays might therefore be important to understand processes involving extended cellular interactions, such as immunological synapse formation. A biologically informative in silico system was created with minimal, high-confidence inputs. Incorporating random effects in surface separation through thermal motion enabled new deductions of the effects of surface-constrained biomolecular function. Important molecular information is embedded in the patterns and statistics of motion

Aromatase inhibitor-associated bone and musculoskeletal effects: new evidence defining etiology and strategies for management

Aromatase inhibitors are widely used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer. While the agents are associated with slightly improved survival outcomes when compared to tamoxifen alone, bone and musculoskeletal side effects are substantial and often lead to discontinuation of therapy. Ideally, the symptoms should be prevented or adequately treated. This review will focus on bone and musculoskeletal side effects of aromatase inhibitors, including osteoporosis, fractures, and arthralgias. Recent advances have been made in identifying potential mechanisms underlying these effects. Adequate management of symptoms may enhance patient adherence to therapy, thereby improving breast cancer-related outcomes

Retinal disease in patients with systemic lupus erythematosus

OBJECTIVE—To investigate the incidence of retinopathy in systemic lupus erythematosus (SLE) and to clarify its significance in relation to other clinical manifestations.
METHODS—A cross sectional study on lupus retinopathy was made in 69 patients with SLE. One expert ophthalmologist examined the ocular fundi of the lupus patients without any information of their disease state. Clinical and laboratory findings in the patients with retinopathy and those without were compared.
RESULTS—Retinopathy was found in 7/69 (10%) patients. The findings included haemorrhages, vasculitis, cotton wool spots, and hard exudates, all of which were considered to reflect vascular damage. Retinopathy was found to be associated with the presence of anticardiolipin antibody (p<0.05) and with central nervous system lupus (p<0.01). The patients with retinopathy had higher levels of serum creatinine than the patients without retinopathy (p<0.01). The disease activity of lupus, as assessed by the maximum SLE disease activity index (SLEDAI) score of the patients, was also significantly higher in the patients with retinopathy (p<0.03).
CONCLUSION—Incidence of retinopathy in SLE was similar to that in previous reports and it may reflect tissue microangiopathy, particularly associated with vasculitis or anticardiolipin antibodies, or both.


Proposition de mesure de la rotation d'une balle par analyse d'images digitales

Ushiyama Y., Tamaki T., Hashimoto O., Igarashi H. Proposition de mesure de la rotation d'une balle par analyse d'images digitales. In: Les Cahiers de l'INSEP, n°35, 2005. Les sports de raquette. Données scientifiques et méthodologiques. Applications pour l'entraînement. pp. 279-280

Validity and failure of the Boltzmann approximation of kinetic annihilation

This paper introduces a new method to show the validity of a continuum description for the deterministic dynamics of many interacting particles. Here the many-particle evolution is analyzed for a hard sphere flow with the addition that after a collision the collided particles are removed from the system. We consider random initial configurations which are drawn from a Poisson point process with spatially homogeneous velocity density f (0)(v). Assuming that the moments of order less than three of f (0) are finite and no mass is concentrated on lines, the homogeneous Boltzmann equation without gain term is derived for arbitrary long times in the Boltzmann-Grad scaling. A key element is a characterization of the many-particle flow by a hierarchy of trees which encode the possible collisions. The occurring trees are shown to have favorable properties with a high probability, allowing us to restrict the analysis to a finite number of interacting particles and enabling us to extract a single-body distribution. A counter-example is given for a concentrated initial density f (0) even to short-term validity