Complementation analysis reveals a potential role of human ARV1 in GPI anchor biosynthesis

ARV1 is involved in regulating lipid homeostasis but also in the biosynthesis of glycosylphosphatidylinositol (GPI) in Saccharomyces cerevisiae. Here, we examined whether human ARV1 can complement the role of yeast ARV1 in GPI biosynthesis. Overexpression of human ARV1 could rescue the phenotypes associated with GPI anchor synthesis defect in the yeast arv1Δ mutant. The results suggest that Arv1 function in GPI biosynthesis may be conserved in all eukaryotes, from yeast to humans. Copyright © 2015 John Wiley & Sons, Ltd.     

Blood Pressure Elevation of Tubular Specific (P)RR Transgenic Mice and Lethal Tubular Degeneration due to Possible Intracellular Interactions between (P)RR and Alternative Renin Products

The prorenin/renin receptor ((P)RR) is a multifunctional protein that is widely distributed in various organs. Despite intensive research for more than 20 years, this receptor has not been fully characterized. In this study, we generated mice overexpressing the tubular epithelial (P)RR gene ((P)RR-TG mice) to test the previously reported functional role of (P)RR by Ramkumar et al. in 2015 using tubular specific (P)RR KO mice. (P)RR-TG mice were maintained and analyzed in individual metabolic cages and were administered angiotensin II blocker (ARB), direct renin inhibitor (DRI), and bafilomycin, that is, vacuolar ATPase (V-ATPase) antagonist. (P)RR-TG mice were hypertensive and had alkalized urine with lower osmolality and Na⁺ excretion. ARB and DRI, but not bafilomycin, concurrently decreased blood pressure. Bafilomycin acidized urine of (P)RR-TG mice, or equivalently this phenomenon restored the effect of overexpressed transgene, suggesting that (P)RR functioned as a V-ATPase in renal tubules. Afterall, (P)RR-TG mice were mated with alternative renin transgenic mice (ARen2-TG), which we identified as intracellular renin previously, to generate double transgenic mice (DT-TG). Lethal renal tubular damage was observed in DT-TG mice, suggesting that intracellular renin may be a ligand for (P)RR in tubules. In summary, (P)RR did not substantially affect the tissue renin-angiotensin system (RAS) in our model of tubular specific (P)RR gene over-expression, but alternative intracellular renin may be involved in (P)RR signaling in addition to conventional V-ATPase function. Further investigations are warranted.     

Inflammation Regulates Haematopoietic Stem Cells and Their Niche

Haematopoietic stem cells (HSCs) reside in the bone marrow and are supported by the specialised microenvironment, a niche to maintain HSC quiescence. To deal with haematopoietic equilibrium disrupted during inflammation, HSCs are activated from quiescence directly and indirectly to generate more mature immune cells, especially the myeloid lineage cells. In the process of proliferation and differentiation, HSCs gradually lose their self-renewal potential. The extensive inflammation might cause HSC exhaustion/senescence and malignant transformation. Here, we summarise the current understanding of how HSC functions are maintained, damaged, or exhausted during acute, prolonged, and pathological inflammatory conditions. We also highlight the inflammation-altered HSC niche and its impact on escalating the insults on HSCs.     

Radiation-induced polymerization of ethylene in a pilot plant. I. Bulk process

Radiation-induced bulk polymerization of ethylene was carried out with use of a pilot plant with a 10 liter reactor at pressures of 225–400 kg/cm², temperatures of 30–95°C, ethylene feed rates of 5–28 kg/hr, and dose rate of 3.8 × 10⁵ rad/hr. Characteristics of the process are mild polymerization conditions and capability of producing medium density polyethylene in powder form. The spacetime yield and molecular weight of polymer were in the range of 3.5 to 13.1 g/liter hr and 2.2 × 10⁴ to 14 × 10⁴, respectively. The space-time yield increased with mean residence time and 2.4 powders of pressure, and decreased with temperature. Molecular weight changed similarly with the reaction conditions. These results were consistent with those of the bench plant experiment and the scale effect was small. Polymer deposit to the reactor wall limited a period of continuous operation of the plant. The amount of deposited polymer was increased with the square of reaction time. The rate of polymer deposit was proportional to polymer concentration and to the cube of pressure. The polymer deposit cannot be solved in the bulk process.     

Model predictive in vitro dissolution testing in pharmaceutical continuous manufacturing: An equivalence study

A predictive mathematical model for tablet dissolution was developed and implemented in an end-to-end integrated continuous manufacturing pilot plant. The tablets were produced for immediate release with a proprietary extrusion-molding-coating (EMC) unit operation. Besides the mass balance of API solute in the buffer solution, the model consisted of the dissolution, diffusion, and population balance of API particles in the swollen tablet, which was mainly controlled by the swelling and erosion of the polymeric excipient matrix. An equivalence study was investigated by comparing the model prediction to the experiments that were conducted according to USP42-NF37 General Chapter <711> Dissolution, during which the drug dose level was varied in a range from 60 to 80 wt%. Consistent equivalence was demonstrated with the similarity factor f₂ > 50 for all sampled tablets. Concluding remarks and industrial perspectives on model predictive in vitro dissolution testing are provided.     

Neutral poly(3,4-ethylenedioxythiophene-2,5-diyl)s: preparation by organometallic polycondensation and their unique p-doping behavior

Neutral and non-doped poly(3,4-ethylenedioxythiophene), PEDOTh(Ni), and its hexyl derivative, PEDOTh-C₆(Ni), have been prepared by organometallic dehalogenation polycondensation of 2,5-dichloro-3,4-ethylenedioxythiophene and its hexyl derivative with a zerovalent nickel complex. PEDOTh-C₆(Ni) was soluble in organic solvents and ¹H NMR data indicated that it had an M_n of 11,000. MALDI-TOF mass analysis of PEDOTh(Ni) gave M_n and M_w of about 1700 and 2400, respectively. PEDOTh-C₆(Ni) showed a UV-Vis absorption peak at 546 nm in CHCl₃. Electrochemical oxidation of PEDOTh-C₆(Ni) started at about −0.40 V vs Ag⁺/Ag and gave a peak at 0.20 V vs Ag⁺/Ag. Chemical and electrochemical oxidation (or p-doping) of PEDOTh-C₆(Ni), both in solutions and in a solid state, led to weakening of the original π-π^∗ peaks and rise of new peak(s) in a region of 800-1500 nm. The p-doping of PEDOTh-C₆(Ni) caused not only a decrease in the intensity of ¹H NMR signals of the bridging ethylene hydrogens but also a decrease in that of the hexyl side chain, suggesting a strong interaction of the p-dopant with the side chain. NMR data of poly(3-methoxythiophene-2,5-diyl) also supported an assumption that p-doping brings about a severe change in electronic state of the substituent attached to the polythiophene main chain. PEDOTh(Ni) had a density of 1.71 g cm⁻³; the molecular packing mode of PEDOTh(Ni) is discussed based on the density of the polymer and its XRD data.     

Growth of High-Quality Pb((Zn1/3Nb2/3)0.91Ti0.09)O3 Single Crystals by Excess ZnO Addition

A high-quality single crystal of Pb((Zn_1/3Nb_2/3)_0.91Ti_0.09)O₃ (PZNT 91/9), 40 mm in diameter and 20 mm in length, was successfully grown using the solution Bridgman method with a slight excess amount of ZnO. High-quality wafers were sliced from the light-brown single crystal. No PbO inclusions or opaque areas were observed in the transparent wafers. An array probe for echocardiography was constructed with the single-crystal wafer, and its superior performance was demonstrated.     

Study on the Anti-Coking Nature of Ni/SrTiO3 Catalysts by the CH4 Pyrolysis

A solid phase crystallization (spc) method was applied for the preparation of SrTiO₃-supported Ni catalysts and compared to the impregnation (imp) method. spc-Ni_0.2/SrTiO₃ has highly dispersed and stable Ni metal particles resulting in higher activity and higher sustainability against coking than imp-Ni_0.2/SrTiO₃ in the partial oxidation of CH₄. Both catalysts were tested for the CH₄ pyrolysis in order to elucidate the catalytic nature against coking of spc-Ni_0.2/SrTiO₃. The amount of carbon and the rate of H₂ formation were similar over both catalysts at both 773 and 1073 K. On both catalysts, CH₄ continuously decomposed at 773 K, while the rate of CH₄ pyrolysis quickly decreased at 1073 K. Fibrous carbons grew up with a Ni metal particle on the tip of the fiber at 773 K, while carbon balls and short carbon fibers with a Ni metal particle encapsulated inside formed and no sufficient growth of the fiber was observed at 1073 K. The carbon species formed at 773 K was hydrogenated completely to CH₄ around 873 K, while the hydrogenation of that formed at 1073 K needed higher temperature around 1073 K. However, the carbon species formed on both the catalysts at either 773 or 1073 K was completely oxidized around 773 K. Thus, judging from the anti-coking nature, the behaviors in the CH₄ pyrolysis are similar over both catalysts, nonetheless spc-Ni_0.2/SrTiO₃ was far superior to imp-Ni_0.2/SrTiO₃ in the CH₄ oxidation. It is likely that the high sustainability against coking of spc-Ni_0.2/SrTiO₃ is not due to its intrinsic nature suppressing the coking but due to its high activity of reforming which can quickly eliminate the carbon formed on the catalyst surface.     

Cholesteryl ester compounds containing alkyl branched acyl groups — their preparations,properties and applications

Cholesterol having a reactive hydroxyl group at C₃-position can react with fatty acids to give the corresponding cholesteryl esters. Most of the natural cholesteryl esters consist of straight alkyl chain fatty acids with a high melting point. In oleochemistry it is well known that alkyl branched fatty acids, which are derived from petroleum or the fat and oil industry, have low melting points (mp.) and are chemically more stable if they are saturated acids. We designed alkyl branched fatty acid cholesteryl esters by means of common esterification and found some esters having a low mp. (mostly as a liquid). They had no irritative effect on both animal and human skin. They showed characteristic emulsification properties, namely the formation of either O/W or W/O emulsion coexistence together with other lipid components. Applying them onto human skin, they were able to penetrate towards the stratum corneum and improve the water-retaining ability and the barrier function of the stratum corneum. Based on these properties we have been applying the alkyl branched fatty acid cholesteryl ester, especially the methyl branched isostearic acid cholesteryl ester (IS-CE), to a shampoo and a rinse as hair cosmetics, skin care cosmetics and bath-additive products in the past decade.