Chemokines Up-Regulated in Epithelial Cells Control Senescence-Associated T Cell Accumulation in Salivary Glands of Aged and Sjögren’s Syndrome Model Mice

Immunosenescence is characterized by age-associated changes in immunological functions. Although age- and autoimmune-related sialadenitis cause dry mouth (xerostomia), the roles of immunosenescence and cellular senescence in the pathogenesis of sialadenitis remain unknown. We demonstrated that acquired immune cells rather than innate immune cells infiltrated the salivary glands (SG) of aged mice. An analysis of isolated epithelial cells from SG revealed that the expression levels of the chemokine CXCL13 were elevated in aged mice. Senescence-associated T cells (SA-Ts), which secrete large amounts of atypical pro-inflammatory cytokines, are involved in the pathogenesis of metabolic disorders and autoimmune diseases. The present results showed that SA-Ts and B cells, which express the CXCL13 receptor CXCR5, accumulated in the SG of aged mice, particularly females. CD4⁺ T cells derived from aged mice exhibited stronger in vitro migratory activity toward CXCL13 than those from young mice. In a mouse model of Sjögren’s syndrome (SS), SA-Ts also accumulated in SG, presumably via CXCL12-CXCR4 signaling. Collectively, the present results indicate that SA-Ts accumulate in SG, contribute to the pathogenesis of age- and SS-related sialadenitis by up-regulating chemokines in epithelial cells, and have potential as therapeutic targets for the treatment of xerostomia caused by these types of sialadenitis.     

Effect of Electron Correlation on Phonon Spectra in Cuprates

We examine theoretically the phonon dynamics in the electron-phonon-coupled systems. The model Hamiltonian is a one-dimensional Hubbard model where the hopping of electrons induces the electron-phonon coupling. The numerically exact diagonalization of the Hamiltonian with truncation of the total number of phonons is performed. We calculate the phonon excitation spectra and find that the softening of phonons occurs in insulating case, and a diffusive character appears in the metallic case. We also calculate the charge and spin excitation spectra and find that the dynamics of the phonon coupled with the hopping of electrons is affected by the low energy charge and spin excitations.     

Markedly compressible behaviors of gellan hydrogels in a constrained geometry at ultraslow strain rates

The fracture behaviors of gellan hydrogels under compression remarkably depend on the strain rate as well as the boundary conditions for lateral expansion. In the geometry with no constraint for lateral expansion (conventional uniaxial compression), the gels rupture at relatively small strains independently of the compression rates. In contrast, when the gels are compressed extremely slowly (at a strain rate of ca. 10⁻⁵ s⁻¹) in the geometry prohibiting the lateral expansion at their top and bottom surfaces, they are remarkably compressible down to 2% of the initial height without macroscopic fracture and they are accompanied by a large amount of water release. In such markedly compressed gels, many microscopic cracks are formed around the central layer, where strain concentration occurs due to the nonuniform deformation arising from the constrained geometry. In the highly compressible case, the formation of macroscopic cracks is prevented by the localization of microscopic cracks as well as the enhancement in mechanical toughness by a significant increase in polymer concentration due to water release.     

A novel brain-derived member of the epidermal growth factor family that interacts with ErbB3 and ErbB4

The availability of an analgesic compound devoid of the side effects associated with the commonly used opioid and nonsteroidal antiinflammatory drugs would be useful during the perioperative period. Although adenosine has analgesic and anesthetic-sparing properties, it also produces dose-dependent cardiovascular depression. Inhibitors of adenosine kinase may be able to provide analgesia without producing acute cardiovascular or respiratory depression. This preliminary study investigated the effects of a novel adenosine kinase-inhibiting drug, GP683, on the minimum alveolar anesthetic concentration (MAC) of desflurane in dogs. Seven mongrel dogs were administered one of three different GP683 dose regimens (or the solvent) by intravenous infusion on separate occasions according to a cross-over study design. After determining the baseline desflurane MAC value, GP683 was infused at 75, 150, or 300 microg x kg(-1) x min(-1) for 5 min as a loading dose, followed by 15, 30, or 60 microg x kg(-1) x min(-1) for an additional 85 min to maintain a stable plasma drug level. The desflurane MAC was redetermined 30-90 min after starting the study drug or vehicle infusion, and 30-90 min and 120-180 min after termination of the infusion. Cardiovascular variables and plasma concentrations of GP683 were determined at specific intervals before, during, and after the MAC determinations. The three GP683 dose regimens produced 22%, 31%, and 50% decreases in the desflurane MAC, respectively. In addition, there was good correlation between the decrease in desflurane MAC and the plasma GP683 concentration (r = -0.78). Although the mean arterial pressure (MAP) was decreased up to 25% by the highest infusion rate of GP683, adjustments in the desflurane concentration to an equi-MAC value resulted in normalization of the MAP values. Furthermore, GP683 produced no changes in heart rate. In conclusion, the adenosine kinase-inhibiting drug, GP683, produced dose-dependent decreases in the desflurane MAC of dogs without producing untoward hemodynamic changes. IMPLICATIONS: An investigational drug (GP683) that can increase the levels of an important endogenous substance in the body (adenosine) has been found to decrease the anesthetic requirement in dogs without producing adverse effects on the cardiovascular system.     

Binding of mutated Ras- and p53-derived peptides to HLA-DR molecules

We investigated retrospectively 132 cases of open wedge high tibial osteotomy using an external fixation device, concentrating on the rate of neurological complications. One group of patients underwent surgery according to the conventional technique (n = 89). The rate of transient neurological complications was 15.7%; 7 months after surgery the rate of persistent deficits was 12.4%. For the second group (n = 43) a modified surgical technique was used that lowered the complication rate significantly (transient deficits 14%, persistent deficits 4.7%). In the modified technique the osteotomy is not performed in the conventional way using an oscillating saw but through consecutive drill holes of increasing diameter followed by osteoclasis. The lower complication rate in the second group is mainly due to the less extensive approach that leads to a smaller number of postoperative tibialis anterior syndromes (type B lesion). No differences were found with type C lesions (extension deficit of D1). No complete peroneal nerve palsy (type A) occurred in either group. We conclude that the reduction of neurological complications in group 2 is related to the less extensive approach of the proposed technique.     

Subsurface structures in initial stage of FeSi2 growth studied by high-resolution Rutherford backscattering spectroscopy

The initial stage of iron silicide formation is investigated by high-resolution Rutherford backscattering spectroscopy. During the Fe deposition on Si(001) at 470 °C, the formation of FeSi₂ is confirmed by the surface peak analysis. Initially, FeSi₂ grows epitaxially so that one of the major crystallographic axes is parallel to the <111> axis of the Si substrate. With increasing Fe deposition, the deviation between the major crystallographic axis of the silicide region and Si<111> increases although the electron diffraction pattern is independent of the amount of Fe deposition. Therefore, the subsurface crystallographic structure of iron silicide is transformed from a cubic-like to a low-symmetry structure.     

Stabilization of bioethanol recovery with silicone rubber‐coated ethanol‐permselective silicalite membranes by controlling the pH of acidic feed solution

In order to produce highly concentrated bioethanol by pervaporation using an ethanol‐permselective silicalite membrane, techniques to suppress adsorption of succinic acid, which is a chief by‐product of ethanol fermentation and causes the deterioration in pervaporation performance, onto the silicalite crystals was investigated. The amount adsorbed increased as the pH of the aqueous succinic acid solution decreased. The pervaporation performance also decreased with decreasing pH when the ternary mixtures of ethanol/water/succinic acid were separated. Using silicalite membranes individually coated with two types of silicone rubber, pervaporation performance was significantly improved in the pH range of 5 to 7, when compared with that of non‐coated silicalite membranes in ternary mixtures of ethanol/water/succinic acid. Moreover, when using a silicalite membrane double‐coated with the two types of silicone rubber, pervaporation performance was stabilized at lower pH values. In the separation of bioethanol by pervaporation using the double‐coated silicalite membrane, removal of accumulated substances having an ultraviolet absorption maximum at approximately 260 nm from the fermentation broth proved to be vital for efficient pervaporation. Copyright © 2005 Society of Chemical Industry     

Fiber-optic devices for local area network application

Recent developments on fiber-optic devices are reviewed from the local area network (LAN) application viewpoint. Future technical trends are also discussed, along with current research activities. In local area network systems, low device cost and easy maintenance or maintenance-free devices are especially required. Light sources and photodetectors suitable for the systems are described. InGaAsP/InP light emitting diodes can cover a broad application field, up to a gigabits per second super high-speed network region. Optical passive devices, which include branching couplers, switches and connectors, are mentioned as essential components. Compact transmitter/receiver module technology is a key factor in realizing optical-fiber local area network systems. An example of 200-Mbit/s transmitter/receiver module is reported.     

Use of a YAP1 overexpression cassette conferring specific resistance to cerulenin and cycloheximide as an efficient selectable marker in the yeast Saccharomyces cerevisiae.

Drug-resistance markers for yeast transformation are useful because they can be applied to strains without auxotrophic mutations. However, they are susceptible to technical difficulties, namely lower transformation efficiency and the appearance of drug-resistant mutants without the marker. To avoid these problems, we have constructed a phosphoglycerate kinase (PGK) promoter-driven YAP1 expression cassette, called PGKp-YAP1. Yeast cells containing PGKp-YAP1 were resistant to cycloheximide, a protein synthesis inhibitor, and also to cerulenin, a fatty acid synthesis inhibitor, but not to other drugs tested. The transformation efficiency of PGKp-YAP1 using cerulenin selection was comparable to that using a URA3 auxotrophic marker when low concentrations of cerulenin were used. Non-transformed drug-resistant colonies did appear on the low-concentration cerulenin plates. However, these non-transformed colonies could easily be identified, based on their cycloheximide sensitivity and/or their resistance to aureobasidin A to which the transformants were sensitive. Therefore, the dual drug resistance of PGKp-YAP1 could be used as an effective selection for PGKp-YAP1 recipient cells. The PGKp-YAP1 marker was used to disrupt the LYS2 gene and to transform an industrial yeast strain, indicating that this marker can be used for efficient and reliable gene manipulations in any Saccharomyces cerevisiae strain.