DAAM Is Required for Thin Filament Formation and Sarcomerogenesis during Muscle Development in Drosophila

During muscle development, myosin and actin containing filaments assemble into the highly organized sarcomeric structure critical for muscle function. Although sarcomerogenesis clearly involves the de novo formation of actin filaments, this process remained poorly understood. Here we show that mouse and Drosophila members of the DAAM formin family are sarcomere-associated actin assembly factors enriched at the Z-disc and M-band. Analysis of dDAAM mutants revealed a pivotal role in myofibrillogenesis of larval somatic muscles, indirect flight muscles and the heart. We found that loss of dDAAM function results in multiple defects in sarcomere development including thin and thick filament disorganization, Z-disc and M-band formation, and a near complete absence of the myofibrillar lattice. Collectively, our data suggest that dDAAM is required for the initial assembly of thin filaments, and subsequently it promotes filament elongation by assembling short actin polymers that anneal to the pointed end of the growing filaments, and by antagonizing the capping protein Tropomodulin.     

Wall shear over high degree stenoses pertinent to atherothrombosis

Atherothrombosis can induce acute myocardial infarction and stroke by progressive stenosis of a blood vessel lumen to full occlusion. Since thrombus formation and embolization may be shear-dependent, we quantify the magnitude of shear rates in idealized severely stenotic coronary arteries (≥75% by diameter) using computational fluid dynamics to characterize the shear environment that may exist during atherothrombosis. Maximum shear rates in severe short stenoses were found to exceed 250,000 s^?1 (9500 dynes/cm²) and can reach a peak value of 425,000 s^?1 for a 98% stenosis. These high shear rates exceed typical shear used for in vitro blood flow experiments by an order of magnitude, indicating the need to examine thrombosis at very high shear rates. Pulsatility and stenosis eccentricity were found to have minor effects on the maximum wall shear rates in severe stenoses. In contrast, increases in the stenosis length reduced the maximum shear to 107,000 s^?1 (98% stenosis), while surface roughness could increase focal wall shear rates to a value reaching 610,000 s^?1 (90% stenosis). The “shear histories” of circulating platelets in these stenoses are far below reported activation thresholds. Platelets may be required to form bonds in 5 μs and resist shear forces reaching 8000 pN per platelet. Arterial thrombosis occurs in the face of pathological high shear stress, creating rapid and strong bonds without prior activation of circulating platelets.     

Trajectories of alpha rhythm dipoles shifting over the human brain cortex

Dynamic study of 3D localization of the equivalent current dipoles (ECD)--sources of the EEG alpha rhythm in the human brain was performed in seven subjects with closed eyes using a one-dipole model. An exact localization of ECDs was obtained by combination of EEG and MRI mapping that allowed tracing of ECD shifts over the cortex with 4 ms step. Our data confirmed localization of these ECDs mainly in the occipital cortex and revealed their successive shift over this area during generation of each alpha-wave. Typical trajectories of these shifts were revealed and quantitatively compared by the hierarchical cluster analysis. The data obtained directly proved periodical rhythmic alpha-wave spreading process in the human visual cortex and an external control of this process. The data are discussed in terms of the "scanning hypothesis" (Pitts W., McCulloch W.H. Bull. Math. Biophys. 1947. V. 9. P. 127) which predicted a certain functional meaning of the alpha activity for cortical processing of sensory information in the human brain.     

Rhythmic photostimulation and a number of alpha-rhythm dipoles in the human brain

Dynamic study of the equivalent current dipoles (ECDs) of alpha rhythm in the human brain was performed in a one-dipole model. The number of ECDs was shown to be dependent on the time course of visual stimulation, on the phase shift of triggering of flickers with alpha-rhythm frequency from alpha-wave, as well as on the type of visual illusions produced in subjects by this stimulation. The data are discussed in accordance with the "scanning hypothesis" that predict a certain functional meaning of the spreading alpha-wave for cortical processing of sensory information in the human brain.     

Theory to Predict Shear Stress on Cells in Turbulent Blood Flow

Shear stress on blood cells and platelets transported in a turbulent flow dictates the fate and biological activity of these cells. We present a theoretical link between energy dissipation in turbulent flows to the shear stress that cells experience and show that for the case of physiological turbulent blood flow: (a) the Newtonian assumption is valid, (b) turbulent eddies are universal for the most complex of blood flow problems, and (c) shear stress distribution on turbulent blood flows is possibly universal. Further we resolve a long standing inconsistency in hemolysis between laminar and turbulent flow using the theoretical framework. This work demonstrates that energy dissipation as opposed to bulk shear stress in laminar or turbulent blood flow dictates local mechanical environment of blood cells and platelets universally.     

Top-down characterization of resource use in LCA: from problem definition of resource use to operational characterization factors for dissipation of elements to the environment

The International Journal of Life Cycle Assessment - The methods for assessing the impact of using abiotic resources in life cycle assessment (LCA) have always been heavily debated. One of the main...