Amphiphilic molecular gels from ω-aminoalkylated l-glutamic acid derivatives with unique chiroptical properties

Self-assembling amphiphiles with unique chiroptical properties were derived from l-glutamic acid through ω-aminoalkylation and double long-chain alkylation. These amphiphiles can disperse in various solvents ranging from water to n-hexane. TEM and SEM observations indicate that the improvement in dispersity is induced by the formation of tubular and/or fibrillar aggregates with nanosized diameters, which makes these amphiphiles similar to aqueous lipid membrane systems. Spectroscopic observations, such as UV–visible and CD spectroscopies indicate that the aggregates are constructed on the basis of S- and R-chirally ordered structures through interamide interactions in water and organic media, respectively, and that these chiroptical properties can be controlled thermotropically and lyotropically. It is also reported that the chiral assemblies provide specific binding sites for achiral molecules and then induce chirality for the bonded molecules. Further, the applicability of the amphiphiles to template polymerization is discussed.     

Differential effects of platelet rich plasma and washed platelets on the proliferation of mouse MSC cells

Multipotent mesenchymal stem cell (MSC) therapies are being tested clinically for a variety of disorders. However, despite the remarkable clinical advancements in this field, most applications still use traditional culture media containing fetal bovine serum. Platelet-rich plasma (PRP) appears as a novel application for tissue engineering and its effect on bone healing is thought to be mainly dependent on the proliferation promoting function, with the molecular mechanisms largely unknown. In this study, mouse osteogenic progenitor mesenchymal stem cells (MSCs) were cultured in PRP or washed platelet (WPLT)-treated wells or in untreated wells, and analyzed on cycloxygenase 2 (COX2) expression (qRT-PCR), cell growth (MTT assay) and cell differentiation (alkaline phosphatase activity). The results showed that PRP and WPLT stimulated cell growth similarly in the first 6 days, together with the steady induction of COX2 and PGE2. 10 μmol/l celecoxib (an inhibitor of COX2) significantly inhibited the pro-proliferation effects. Interestingly, WPLT had stronger effects than PRP in proliferation at the later time points (6–9 days). ALP activity assay and collagen 1a expression revealed PRP had a mild but statistically significant pro-differentiation effect, while no obvious effects observed in WLPT group. In summary, PRP stimulates initial growth of MSCs in a COX2 partially dependent manner and the less obvious osteogenic differentiation promoting effects of WPLT strongly indicates WPLT rather than the PRP should be the optional choice for expanding MSCs in vitro for clinical use.     

Purification and properties of the membrane-bound NADH oxidase of a facultatively anaerobic alkaliphile

A membrane-bound NADH oxidase of an anaerobic alkaliphile, M-12 (a strain of Amphibacillus sp.), was solubilized with decanoyl N-methylglucamide and purified by chromatography on DEAE-Sepharose and hydroxyapatite. The purified enzyme appears to consist of a single polypeptide component with an apparent molecular mass of 56 kDa. The enzyme catalyzed the oxidation of NADH with the formation of H₂O₂ and exhibited a specific activity of 46 μmol NADH min^–1 (mg protein)^–1. NADPH did not serve as a substrate for the enzyme. The K _m for NADH was estimated to be 0.05 mM. The enzyme exhibited a pH dependence for activity, with a pH optimum at approximately 9.5. The enzyme required a high concentration of salt and exhibited maximum activity in the presence of 600 mM NaCl. Received: 3 August 1998 / Accepted: 23 December 1998     

OTUD1 deubiquitinase regulates NF-κB- and KEAP1-mediated inflammatory responses and reactive oxygen species-associated cell death pathways

Deubiquitinating enzymes (DUBs) regulate numerous cellular functions by removing ubiquitin modifications. We examined the effects of 88 human DUBs on linear ubiquitin chain assembly complex (LUBAC)-induced NF-κB activation, and identified OTUD1 as a potent suppressor. OTUD1 regulates the canonical NF-κB pathway by hydrolyzing K63-linked ubiquitin chains from NF-κB signaling factors, including LUBAC. OTUD1 negatively regulates the canonical NF-κB activation, apoptosis, and necroptosis, whereas OTUD1 upregulates the interferon (IFN) antiviral pathway. Mass spectrometric analysis showed that OTUD1 binds KEAP1, and the N-terminal intrinsically disordered region of OTUD1, which contains an ETGE motif, is indispensable for the KEAP1-binding. Indeed, OTUD1 is involved in the KEAP1-mediated antioxidant response and reactive oxygen species (ROS)-induced cell death, oxeiptosis. In Otud1^−/−-mice, inflammation, oxidative damage, and cell death were enhanced in inflammatory bowel disease, acute hepatitis, and sepsis models. Thus, OTUD1 is a crucial regulator for the inflammatory, innate immune, and oxidative stress responses and ROS-associated cell death pathways.Subject terms: Stress signalling, Cell death, Inflammation     

Effects of space flight on the histological characteristics of the aortic depressor nerve in the adult rat: electron microscopic analysis.

The effects of microgravity on the histological characteristics of the aortic depressor nerve, which is the afferent of the aortic baroreflex arc, were determined in 10 female adult rats. The rats were assigned for nursing neonates in the Space Shuttle Columbia or in the animal facility on the ground (NASA Neurolab, STS-90), and were housed for 16 days under microgravity in space (microg, n=5) or under one force of gravity on Earth (one-g, n=5). In the Schwann cell unit in which the axons of unmyelinated fibers are surrounded by one Schwann cell, the average number of axons per unit in the microg group was 2.1 +/- 1.6 (mean +/- SD, n=312) and significantly less than that in the one-g group (3.0 +/- 2.9, n=397, p<0.05). The proportion of unmyelinated fibers in the aortic depressor nerve in the microg group was 64.5 +/- 4.4% and significantly less than that in the one-g group (74.0 +/- 7.3%, p<0.05). These results show that there is a decrease in the number of high-threshold unmyelinated fibers in the aortic depressor nerve in adult rats flown on the Shuttle Orbiter, suggesting that the aortic baroreflex is depressed under microgravity during space flight.     

Biophoton Emission Induced by Heat Shock

Ultraweak biophoton emission originates from the generation of reactive oxygen species (ROS) that are produced in mitochondria as by-products of cellular respiration. In healthy cells, the concentration of ROS is minimized by a system of biological antioxidants. However, heat shock changes the equilibrium between oxidative stress and antioxidant activity, that is, a rapid rise in temperature induces biophoton emission from ROS. Although the rate and intensity of biophoton emission was observed to increase in response to elevated temperatures, pretreatment at lower high temperatures inhibited photon emission at higher temperatures. Biophoton measurements are useful for observing and evaluating heat shock.     

Sustained Effect of Hyaluronic Acid in Subcutaneous Administration to the Cochlear Spiral Ganglion

The spatiotemporal distribution of drugs in the inner ear cannot be precisely evaluated because of its small area and complex structure. In the present study, we used hyaluronic acid (HA)-dispersed luciferin to image transgenic mice and to determine the effect of HA on controlled drug delivery to the cochlea. GFAP-luc mice, which express luciferase in cochlear spiral ganglion cells, were subcutaneously administered HA-luciferin (HA-sc) or luciferin dissolved in saline (NS-sc) or intraperitoneally administered luciferin dissolved in saline (NS-ip). The bioluminescence of luciferin was monitored in vivo in real time. The peak time and half-life of fluorescence emission were significantly increased in HA-sc-treated mice compared with those in NS-sc- and NS-ip-treated mice; however, significant differences were not observed in peak photon counts. We detected differences in the pharmacokinetics of luciferin in the inner ear, including its sustained release, in the presence of HA. The results indicate the clinical potential of using HA for controlled drug delivery to the cochlea.