Flow goes forward and cells step backward: endothelial migration

Systemic and pulmonary circulations constitute a complex organ that serves multiple important biological functions. Consequently, any pathological processing affecting the vasculature can have profound systemic ramifications. Endothelial and smooth muscle are the two principal cell types composing blood vessels. Critically, endothelial proliferation and migration are central to the formation and expansion of the vasculature both during embryonic development and in adult tissues. Endothelial populations are quite heterogeneous and are both vasculature type- and organ-specific. There are profound molecular, functional, and phenotypic differences between arterial, venular and capillary endothelial cells and endothelial cells in different organs. Given this endothelial cell population diversity, it has been challenging to determine the origin of endothelial cells responsible for the angiogenic expansion of the vasculature. Recent technical advances, such as precise cell fate mapping, time-lapse imaging, genome editing, and single-cell RNA sequencing, have shed new light on the role of venous endothelial cells in angiogenesis under both normal and pathological conditions. Emerging data indicate that venous endothelial cells are unique in their ability to serve as the primary source of endothelial cellular mass during both developmental and pathological angiogenesis. Here, we review recent studies that have improved our understanding of angiogenesis and suggest an updated model of this process.Subject terms: Cell lineage, Chemotaxis     

Identification of New Non-BBB Permeable Tryptophan Hydroxylase Inhibitors for Treating Obesity and Fatty Liver Disease

Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC₅₀ value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation.     

Tomatidine-stimulated maturation of human embryonic stem cell-derived cardiomyocytes for modeling mitochondrial dysfunction

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) have been reported to exhibit immature embryonic or fetal cardiomyocyte-like phenotypes. To enhance the maturation of hESC-CMs, we identified a natural steroidal alkaloid, tomatidine, as a new substance that stimulates the maturation of hESC-CMs. Treatment of human embryonic stem cells with tomatidine during cardiomyocyte differentiation stimulated the expression of several cardiomyocyte-specific markers and increased the density of T-tubules. Furthermore, tomatidine treatment augmented the number and size of mitochondria and enhanced the formation of mitochondrial lamellar cristae. Tomatidine treatment stimulated mitochondrial functions, including mitochondrial membrane potential, oxidative phosphorylation, and ATP production, in hESC-CMs. Tomatidine-treated hESC-CMs were more sensitive to doxorubicin-induced cardiotoxicity than the control cells. In conclusion, the present study suggests that tomatidine promotes the differentiation of stem cells to adult cardiomyocytes by accelerating mitochondrial biogenesis and maturation and that tomatidine-treated mature hESC-CMs can be used for cardiotoxicity screening and cardiac disease modeling.Subject terms: Heart failure, Embryonic stem cells, Stem-cell differentiation     

Curing temperature- and concentration-dependent dielectric properties of cross-linked poly-4-vinylphenol (PVP)

In this paper, dielectric properties of various thick PVP films cured at temperatures between 125° C and 200 °C are investigated. The thicknesses of PVP films are adjusted by varying their concentration in PGMEA solvent from 10 wt% to 2.5 wt%. Through FT-IR, C–V, SEM, and AFM analyses, the optimum curing process temperatures (150 °C for 10 wt% and 7.5 wt% samples, and 175 °C for 5 wt% samples) where PET substrates can be thermally endured are proposed in terms of their low hysteresis voltage in the C–V curve (1–2 V in 10 wt% samples, below 1 V in 7.5 wt% samples, and 0.5 V in 5 wt% samples).     

Talbot interferometer with computer generated gratings

In a Talbot interferometer the self image of a periodic pattern, such as a Ronchi ruling of period d, illuminated by a monochromatic plane wavefront of wavelength λ, is formed at distances which are integral multiples of 2d²/λ. A refracting object placed in front of the Ronchi ruling distorts the self image. A computer generated pattern can be designed, such that, when placed in a self imaging plane, a uniform intensity or a distinct moire pattern characterising a standard object is obtained. A method of computing the required patterns and experimental results for some aspherical objects are described.     

On the characterization of continuum structure functions

A continuum structure function is a non-decreasing mapping from the unit hypercube to the unit interval. Within the class of continuum structure functions, new axiomatic characterizations of the Natvig and the Barlow-Wu subclass are obtained.     

Off-peak saturation effects of beam-plasma instability

For beam-plasma instability in the absence of a magnetic field, hybrid simulations produce almost identical results to those of particle simulations (both agree with linear and nonlinear analyses), but with much reduced computing cost and noise level. With the verification by simulations, it is shown that the saturation level is very strongly influenced by the discrete wave number spectrum, sometimes giving different, by an order of magnitude, results by choosing slightly different off-peak (in growth rate curve) parameters, which must be considered in most simulations (whether hybrid or particle or whether magnetized or unmagnetized)     

Photonic crystal fiber coupler

Fiber couplers made with photonic crystal fibers (PCF) are reported. Two types of PCF were fabricated by means of stacking a group of silica tubes around a silica rod and drawing them. The fiber couplers were made by use of the fused biconical tapered method. With a fiber that had five hexagonally stacked layers of air holes, a 33/67 coupling ratio was obtained, and with a one-layer four-hole fiber, a 48/52 coupling ratio was obtained. The fabrication processes and the characteristics of the PCFs and the PCF couplers are presented.     

Long range relationship between Morse and Lennard–Jones potential energy functions

Arising from the use of the Morse function–which is well-known for its applicability for describing bonded interaction energy–in van der Waals systems, an attempt is made herein to express parameters of the Lennard–Jones potential function in terms of the Morse function to enable normalized comparison. In a departure from previous work where the parameter relationships enforce equal curvature at the minimum well-depth, the present approach replaces this rule with equal area above the curves for 1?≤?(r/R)?≤?∞. Results show good approximations of the Morse function to the Lennard–Jones curve and vice versa. Comparison with the previous relation for short range interaction shows that the present relations offer superior agreement with the Lennard–Jones function over a longer range. The conversion relations provide a cost-effective, less time-consuming and reasonably reliable method for obtaining Morse parameters from those of the Lennard–Jones function and vice versa.