Morphometric Reconstruction of Coronary Vasculature Incorporating Uniformity of Flow Dispersion

Experimental limitations in measurements of coronary flow in the beating heart have led to the development of in silico models of reconstructed coronary trees. Previous coronary reconstructions relied primarily on anatomical data, including statistical morphometry (e.g., diameters, length, connectivity, longitudinal position). Such reconstructions are non-unique, however, often leading to unrealistic predicted flow features. Thus, it is necessary to impose physiological flow constraints to ensure realistic tree reconstruction. Since a vessel flow depends on its diameter to fourth power, diameters are the logical candidates to guide vascular reconstructions to achieve realistic flows. Here, a diameter assignment method was developed where each vessel diameter was determined depending on its downstream tree size, aimed to reduce flow dispersion to within measured range. Since the coronary micro-vessels are responsible for a major portion of the flow resistance, the auto regulated coronary flow was analyzed in a morphometry-based reconstructed 400 vessel arterial microvascular sub-tree spanning vessel orders 1–6. Diameters in this subtree were re-assigned based on the flow criteria. The results revealed that diameter re-assignment, while adhering to measured morphometry, significantly reduced the flow dispersion to realistic levels while adhering to measured morphometry. The resulting network flow has longitudinal pressure distribution, flow fractal nature, and near-neighboring flow autocorrelation, which agree with measured coronary flow characteristics. Collectively, these results suggest that a realistic coronary tree reconstruction should impose not only morphometric data but also flow considerations. The work is of broad significance in providing a novel computational framework in the field of coronary microcirculation. It is essential for the study of coronary circulation by model simulation, based on a realistic network structure

Promotion of protocell self-assembly from mixed amphiphiles at the origin of life

Vesicles formed from single-chain amphiphiles (SCAs) such as fatty acids probably played an important role in the origin of life. A major criticism of the hypothesis that life arose in an early ocean hydrothermal environment is that hot temperatures, large pH gradients, high salinity and abundant divalent cations should preclude vesicle formation. However, these arguments are based on model vesicles using 1–3 SCAs, even though Fischer–Tropsch-type synthesis under hydrothermal conditions produces a wide array of fatty acids and 1-alkanols, including abundant C10–C15 compounds. Here, we show that mixtures of these C10–C15 SCAs form vesicles in aqueous solutions between pH ~6.5 and >12 at modern seawater concentrations of NaCl, Mg2+ and Ca2+. Adding C10 isoprenoids improves vesicle stability even further. Vesicles form most readily at temperatures of ~70 °C and require salinity and strongly alkaline conditions to self-assemble. Thus, alkaline hydrothermal conditions not only permit protocell formation at the origin of life but actively favour it

Role of Coronary Myogenic Response in Pressure-Flow Autoregulation in Swine: A Meta-Analysis With Coronary Flow Modeling

Myogenic responses (pressure-dependent contractions) of coronary arterioles play a role in autoregulation (relatively constant flow vs. pressure). Publications on myogenic reactivity in swine coronaries vary in caliber, analysis, and degree of responsiveness. Further, data on myogenic responses and autoregulation in swine have not been completely compiled, compared, and modeled. Thus, it has been difficult to understand these physiological phenomena. Our purpose was to: (a) analyze myogenic data with standard criteria; (b) assign results to diameter categories defined by morphometry; and (c) use our novel multiscale flow model to determine the extent to which ex vivo myogenic reactivity can explain autoregulation in vivo. When myogenic responses from the literature are an input for our model, the predicted coronary autoregulation approaches in vivo observations. More complete and appropriate data are now available to investigate the regulation of coronary blood flow in swine, a highly relevant model for human physiology and disease

Nucleobases bind to and stabilize aggregates of a prebiotic amphiphile, providing a viable mechanism for the emergence of protocells

Primordial cells presumably combined RNAs, which functioned as catalysts and carriers of genetic information, with an encapsulating membrane of aggregated amphiphilic molecules. Major questions regarding this hypothesis include how the four bases and the sugar in RNA were selected from a mixture of prebiotic compounds and colocalized with such membranes, and how the membranes were stabilized against flocculation in salt water. To address these questions, we explored the possibility that aggregates of decanoic acid, a prebiotic amphiphile, interact with the bases and sugar found in RNA. We found that these bases, as well as some but not all related bases, bind to decanoic acid aggregates. Moreover, both the bases and ribose inhibit flocculation of decanoic acid by salt. The extent of inhibition by the bases correlates with the extent of their binding, and ribose inhibits to a greater extent than three similar sugars. Finally, the stabilizing effects of a base and ribose are additive. Thus, aggregates of a prebiotic amphiphile bind certain heterocyclic bases and sugars, including those found in RNA, and this binding stabilizes the aggregates against salt. These mutually reinforcing mechanisms might have driven the emergence of protocells