Sequestration of muscarinic acetylcholine receptor m2 subtypes. Facilitation by G protein-coupled receptor kinase (GRK2) and attenuation by a dominant-negative mutant of GRK2

Sequestration of m2 receptors (muscarinic acetylcholine receptor m2 subtypes), which was assessed as loss of N-[3H]methylscopolamine ([3H]NMS) binding activity from the cell surface, was examined in COS 7 and BHK-21 cells that had been transfected with expression vectors encoding the m2 receptor and, independently, vectors encoding a G protein-coupled receptor kinase (GRK2) (beta-adrenergic receptor kinase 1) or a GRK2 dominant-negative mutant (DN-GRK2). The sequestration of m2 receptors became apparent when the cells were treated with 10(-5) M or higher concentrations of carbamylcholine. In this case, approximately 40% or 20-25% of the [3H]NMS binding sites on COS 7 or BHK-21 cells, respectively, were sequestered with a half-life of 15-25 min. In cells in which GRK2 was also expressed, the sequestration became apparent in the presence of 10(-7) M carbamylcholine. Approximately 40% of the [3H]NMS binding sites on both COS 7 and BHK-21 cells were sequestered in the presence of 10(-6) M or higher concentrations of carbamylcholine. When DN-GRK2 was expressed in COS 7 cells, the proportion of [3H]NMS binding sites sequestered in the presence of 10(-5) M or higher concentrations of carbamylcholine was reduced to 20-30%. These results indicate that the phosphorylation of m2 receptors by GRK2 facilitates their sequestration. These results are in contrast with the absence of a correlation between sequestration and the phosphorylation of beta-adrenergic receptors by the GRK2 and suggests that the consequences of phosphorylation by GRK2 are different for different receptors.     

Information systems effectiveness: research designs for causal inference

Abstract. This paper examines the capacity of the research designs of 37 empirical studies of information systems (IS) effectiveness to provide a basis for the development of theories about behaviour related to IS effectiveness. The power of each study to support causal inference was evaluated in terms of (a) its handling of the time dimension, (b) its ability to weigh differences and (c) its resistance to internal validity threats that pose alternative explanations for its reported findings. Of the reviewed studies, 29.7% could account for the time dimension, 32.4% employed a comparison group and 16.2% were not susceptible to any internal validity threats. Only 13.5% of the studies combined an accounting for the time dimension with the use of a comparison group. Of these, however, only 5.4% were also invulnerable to internal validity threats. The research designs of nearly 95% of these published studies were deficient in supporting causal inference. In those studies, suggestions that one variable was causally related to another variable could not be substantiated. Encouragement for the future capacity of IS effectiveness research to support causal inference was found in a trend towards the use of quasiexperimental designs. Recommendations are made regarding ways to increase the inferential capacity of research designs employed in the study of IS effectiveness.     

Evaluation of hydrological processes in a mountainous small basin using a quinone biomarker.

An applicability of quinone biomarker to the analysis of hillslope runoff was investigated. At first, quinone profiles of three streams as well as a hillslope runoff in a forested headwater catchment were compared. The quinone composition of hillslope runoff differed from others. Moreover, there were remarkable differences in quinone profile of hillslope runoff under different rainfall conditions. Then, the behavior of quinone biomarker during the increase and decrease of hillslope runoff after a rainfall event was examined. The fractional changes in Q-9 (H2), Q-10 (H2), Q-11, MK-6 and MK-10 suggested the effect of interflow.     

Changes in Aging Behavior and Defect Structure of Yttria-Fully-Stabilized ZrO2 with Sc2O3 Doping

Methods of suppressing decreased conductivity in 8 mol% Y₂O₃-stabilized–92 mol% ZrO₂ (8YSZ) with aging were investigated. Different amounts of Sc₂O₃ were doped into 8YSZ. The electrochemical properties of Sc₂O₃-doped 8YSZ were measured, and the microstructural and local structural changes were characterized. The present results indicate that an appropriate amount of Sc₂O₃ doping, 3 or 4 mol%, effectively suppresses decreased conductivity with aging in 8YSZ.     

Mutations in the N-terminal globular domain of the type X collagen gene (COL10A1) in patients with Schmid metaphyseal chondrodysplasia

STATEMENT OF PROBLEM: Improved dental stone has been widely used for producing dies for the fabrication of restorations with the lost-wax technique. Improved dental stone is used for several reasons, but it is selected most often because of its reasonable cost, ease of use, and ability to produce consistent results. PURPOSE: This study evaluated the ability of an epoxy resin die material and a type IV dental stone to dimensionally reproduce a custom-fabricated metal die. MATERIAL AND METHODS: Dies were fabricated and measurements were made from three reference lines. Measurements were repeated three times for the master die and for the specimen dies. A mean measurement and percent relative change for each dimension was calculated. RESULTS: A significant difference in the relative change for die height was found between the groups studied (p < 0.003). CONCLUSIONS: This epoxy die system will provide a degree of dimensional accuracy comparable to gypsum when used with addition silicone impression material.     

Identification of Tumor Suppressive Genes Regulated by miR-31-5p and miR-31-3p in Head and Neck Squamous Cell Carcinoma

We identified the microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC) tissues by RNA sequencing, in which 168 miRNAs were significantly upregulated, including both strands of the miR-31 duplex (miR-31-5p and miR-31-3p). The aims of this study were to identify networks of tumor suppressor genes regulated by miR-31-5p and miR-31-3p in HNSCC cells. Our functional assays showed that inhibition of miR-31-5p and miR-31-3p attenuated cancer cell malignant phenotypes (cell proliferation, migration, and invasion), suggesting that they had oncogenic potential in HNSCC cells. Our in silico analysis revealed 146 genes regulated by miR-31 in HNSCC cells. Among these targets, the low expression of seven genes (miR-31-5p targets: CACNB2 and IL34; miR-31-3p targets: CGNL1, CNTN3, GAS7, HOPX, and PBX1) was closely associated with poor prognosis in HNSCC. According to multivariate Cox regression analyses, the expression levels of five of those genes (CACNB2: p = 0.0189; IL34: p = 0.0425; CGNL1: p = 0.0014; CNTN3: p = 0.0304; and GAS7: p = 0.0412) were independent prognostic factors in patients with HNSCC. Our miRNA signature and miRNA-based approach will provide new insights into the molecular pathogenesis of HNSCC.     

Thermal behaviour of TiO2-encapsulating polymers

Comparing the thermal properties of TiO₂ encapsulating polystyrene and poly(methyl methacrylate) with those of TiO₂ dispersion polymers it was found that the encapsulating polymers have two thermal relaxation regions. The activation energy of those thermal relaxation regions was determined using the Wunderlich method and it was found that the values are similar to the activation energy for the dynamic dispersion. It is suggested that the low-temperature thermal relaxation is caused by the local change of conformation of molecular chains, while the high-temperature thermal relaxation is similar to that of the normal glass transition temperature including the interaction with TiO₂. In addition, the thermal behaviour near the degradation point in different atmospheres indicates that the encapsulating polymer has a specific structure for adsorbing a large amount of oxygen.     

Plasma etching durability of poly(methyl methacrylate)

The decomposition of poly(methyl methacrylate) (PMMA), as a positive resist, in CF₄/O₂ plasma etching has been studied in the thin film state in order to clarify the factors influencing the dry etching durability of resists. It becomes clear that the major PMMA decomposition in CF₄/O₂ plasma etching proceeds by the mechanism of random chain scission because very small kinetic chain lengths are estimated from the gel permeation chromatography data. The Arrhenius plots for the plasma etching rate of PMMA bend above about the glass transition temperature (T_g), where rapid increase of the etching rate and remarkable pattern deformation are observed. Activation energy of the PMMA etching rate which is changed by oxygen concentration and rf power indicates various values from 3.1 to 6.5 kcal/mol below about T_g. The result of molecular weight variation in the cross section of the film suggests that the active species permeate into the film with fairly large speed and the PMMA decomposition occurs not only at the film surface but also at deep layer of the film.     

Ketones from carboxylic acids over supported magnesium oxide and related catalysts

Silica-supported alkaline earth oxides revealed excellent activity to convert acetic acid selectively into acetone in a vapor-phase fixed-bed flow system. Acetone was obtained through the cyclic formation of alkaline earth acetate followed by decomposition. Magnesium oxide should be supported on the silica surface without formation of magnesium silicate, which was inactive for the present reaction. Attempted syntheses of benzophenone and acetophenone are also described.     

Enzymatic syntheses of N-lauroyl-β-alanine homologs in organic media

Enyzmatic amidation of the primary amines β-alanine ethyl ester and 3-aminopropionitrile with methyl laurate by means of immobilized lipase (Candida antarctica lipase, CAL) resulted in the formation in good yield of N-lauroyl-β-alanine ethyl ester and 3-(N-lauroylamino)-propionitrile, respectively. When 3-amino-propionitrile was used as substrate, diisopropyl ether was a suitable solvent. Changing the reaction temperature (12–80°C) did not affect the yields, and room temperature was a suitable temperature for this reaction. In the investigation of reaction conditions, the use of equimolar amounts (5 mmol) of substrate and ester, along with 0.5 g of CAL, in diisopropyl ether gave the best yield (99.3%) after 24 h of incubation at 24°C. The enzyme activity in the amidation reaction did not decrease even after six uses. With β-alanine ethyl ester hydrochloride as substrate, diisopropyl ether was unsuited as a solvent owing to the low solubility of the substrate in this solvent. In this reaction, the best yield (82.0%) was attained by using dioxane as solvent. CAL achieved higher extents of amide synthesis with long-chain than with short-chain ester substrates. The enzyme accepted only nonbulky primary amines as substrates.