Molecular Mechanisms for the Regulation of Insulin-Stimulated Glucose Uptake by Small Guanosine Triphosphatases in Skeletal Muscle and Adipocytes

Insulin is a hormone that regulates the blood glucose level by stimulating various physiological responses in its target tissues. In skeletal muscle and adipose tissue, insulin promotes membrane trafficking of the glucose transporter GLUT4 from GLUT4 storage vesicles to the plasma membrane, thereby facilitating the uptake of glucose from the circulation. Detailed mechanisms underlying insulin-dependent intracellular signal transduction for glucose uptake remain largely unknown. In this article, I give an overview on the recently identified signaling network involving Rab, Ras, and Rho family small guanosine triphosphatases (GTPases) that regulates glucose uptake in insulin-responsive tissues. In particular, the regulatory mechanisms for these small GTPases and the cross-talk between protein kinase and small GTPase cascades are highlighted.     

A QoS-aware routing mechanism for multi-channel multi-interface ad-hoc networks

To accommodate real-time multimedia application while satisfying application QoS requirements in a wireless ad-hoc network, we need QoS control mechanisms. In this paper, we propose a new routing mechanism to support real-time multimedia communication by efficiently utilize the limited wireless network capacity. Our mechanism considers a wireless ad-hoc network composed of nodes equipped with multiple network interfaces to each of which a different wireless channel can be assigned. By embedding information about channel usage in control messages of OLSRv2, each node obtains a view of topology and bandwidth information of the whole network. Based on the obtained information, a source node determines a logical path with the maximum available bandwidth to satisfy application QoS requirements. Through simulation experiments, we confirmed that our proposal effectively routed multimedia packets over a logical path avoiding congested links. As a result, the load on a network is well distributed and the network can accommodate more sessions than QOLSR. We also conducted practical experiments using wireless ad-hoc relay nodes with four network interfaces and verified the practicality of our proposal.     

Synthesis and property study on Eu(III) complexes of modified poly(N-isopropylacrylamide)

Poly(N-isopropylacrylamide) with aromatic end groups (Ar-PNIPAM) were synthesized by atom transfer radical polymerization of N-isopropylacrylamide in isopropanol using phenyl 2-chloropropionate, (4′-phenyl)phenyl 2-chloropropionate, and (2′,6′-diphenyl)phenyl 2-chloropropionate as initiators and CuCl/tris(2-dimethylaminoethyl)amine (Me₆TREN) as a catalytic system. The resulting polymers had narrow polydispersity index of 1.10–1.14 and molecular weights of 3700–4600 g mol⁻¹. Then, novel functional complexes of Ar-PNIPAM, Europium(III) (Eu(III)), and α-Thenoyltrifluoroacetone (TTA) (Ar-PNIPAM/Eu(III)/TTA) with thermosensitive and fluorescent properties were synthesized and characterized by Fourier transform infrared spectra and fluorescence spectroscopy. Metal Eu(III) was not only bonded to oxygen and nitrogen atoms of polymer chain in PNIPAM, but also bonded to TTA. The maximum emission intensity of the complexes at 613 nm was enhanced about 22, 27, 33 times compared with that of the corresponding Eu(III). The lower critical solution temperatures (LCSTs) of Ar-PNIPAM/Eu(III)/TTA were slightly greater compared with that of PNIPAM. Eu(III) complexes had excellent fluorescence performance, the fluorescence spectrum presented characteristic emission of Eu(III) at 613 nm.     

Elevated Expression of CCN3 in Articular Cartilage Induces Osteoarthritis in Hip Joints Irrespective of Age and Weight Bearing

Osteoarthritis (OA) occurs not only in the knee but also in peripheral joints throughout the whole body. Previously, we have shown that the expression of cellular communication network factor 3 (CCN3), a matricellular protein, increases with age in knee articular cartilage, and the misexpression of CCN3 in cartilage induces senescence-associated secretory phenotype (SASP) factors, indicating that CCN3 promotes cartilage senescence. Here, we investigated the correlation between CCN3 expression and OA degenerative changes, principally in human femoral head cartilage. Human femoral heads obtained from patients who received total hip arthroplasty were categorized into OA and femoral neck fracture (normal) groups without significant age differences. Gene expression analysis of RNA obtained from femoral head cartilage revealed that CCN3 and MMP-13 expression in the non-weight-bearing part was significantly higher in the OA group than in the normal group, whereas the weight-bearing OA parts and normal cartilage showed no significant differences in the expression of these genes. The expression of COL10A1, however, was significantly higher in weight-bearing OA parts compared with normal weight-bearing parts, and was also higher in weight-bearing parts compared with non-weight-bearing parts in the OA group. In contrast, OA primary chondrocytes from weight-bearing parts showed higher expression of CCN3, p16, ADAMTS4, and IL-1β than chondrocytes from the corresponding normal group, and higher ADAMTS4 and IL-1β in the non-weight-bearing part compared with the corresponding normal group. Acan expression was significantly lower in the non-weight-bearing group in OA primary chondrocytes than in the corresponding normal chondrocytes. The expression level of CCN3 did not show significant differences between the weight-bearing part and non-weight-bearing part in both OA and normal primary chondrocytes. Immunohistochemical analysis showed accumulated CCN3 and aggrecan neoepitope staining in both the weight-bearing part and non-weight-bearing part in the OA group compared with the normal group. The CCN3 expression level in cartilage had a positive correlation with the Mankin score. X-ray analysis of cartilage-specific CCN3 overexpression mice (Tg) revealed deformation of the femoral and humeral head in the early stage, and immunohistochemical analysis showed accumulated aggrecan neoepitope staining as well as CCN3 staining and the roughening of the joint surface in Tg femoral and humeral heads. Primary chondrocytes from the Tg femoral head showed enhanced expression of Ccn3, Adamts5, p16, Il-6, and Tnfα, and decreased expression of Col2a1 and -an. These findings indicate a correlation between OA degenerative changes and the expression of CCN3, irrespective of age and mechanical loading. Furthermore, the Mankin score indicates that the expression level of Ccn3 correlates with the progression of OA.     

Increased Synovial CD14 mRNA Expression and Proportion of CD14high Subsets in Early-Stage Hip Osteoarthritis: Propensity Matched Score Analysis

The pathophysiology of early-stage hip osteoarthritis (EOA) is not fully understood. Although a previous study in an age-unmatched cohort reported that the number of macrophages was increased in knee EOA compared to late OA (LOA), it remained unclear whether increased macrophages in EOA accurately reflect EOA pathology. We investigated the differences in CD14 expression levels between EOA and LOA using age-unmatched and -matched cohorts. Synovial tissues were obtained from 34 EOA (Tönnis grades 0 and 1) and 80 LOA (Tönnis grades 2 and 3) patients. To correct for differences in demographics between patients with LOA and EOA, we also created propensity score-matched cohorts (16 EOA and 16 LOA). CD14 expression and its association with pain was estimated in LOA and EOA before and after propensity matching. We performed flow cytometry on tissues from the 16 patients, with 8 from each group, to assess for CD14+ subsets in the cells. The CD14 expression in EOA was higher than that in LOA both before and after propensity matching. The proportion of CD14^high subsets in EOA was higher than that in LOA. The CD14 expression was associated with pain in EOA before matching. However, no difference was observed between the pain and CD14 expression after matching in EOA. The increased CD14 expression and the proportion of CD14^high subsets may be important features associated with hip EOA pathology. To accurately compare early and late OA, the analysis of a propensity score-matched cohort is necessary.     

A xanthine oxidase inhibitor 1'-acetoxychavicol acetate inhibits azoxymethane-induced colonic aberrant crypt foci in rats

The modifying effect of dietary administration of a xanthine oxidase inhibitor 1'-acetoxychavicol acetate (ACA) present in an edible plant Languas galanga in Thailand on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in rats. Male F344 rats were given s.c. injections of AOM (15 mg/kg body wt) once a week for 3 weeks to induce colonic ACF. They were fed the diets containing 100 or 200 ppm ACA for 5 weeks, starting 1 week before the first dosing of AOM. At the termination of the study (week 5), AOM induced 118 +/- 28 ACF/colon. Dietary administration of ACA caused significant reduction in the frequency of ACF (41% inhibition by 100 ppm ACA feeding and 37% inhibition by 200 ppm ACA feeding, P<0.01). Such inhibition might be associated with suppression of the proliferation biomarkers' expression such as ornithine decarboxylase activity in the colonic mucosa, number of silver-stained nucleolar organizer regions' protein in the colonic mucosal cell nuclei and blood polyamine content. These results indicate that ACA could inhibit the development of AOM-induced ACF through its suppression of cell proliferation in the colonic mucosa and ACA might be a possible chemopreventive agent against colon tumourigenesis.     

Preparation and Characterization of LaxC60 Thin Films Fabricated by Layer-by-Layer Deposition

A modification of physical properties of solid-state C₆₀ when La was doped to C₆₀ thin film as a trivalent metal was examined. the thin film was fabricated by using Layer-by-Layer deposition technique with the multi-sources evaporation system. We found that the C₆₀ film changes its electrical character from the insulator to the semiconductor rapidly upon La doping. the temperature dependence of the electrical conductivity is semiconductive with the activation energy of about 0.3eV.