Two Distinct Pathways Mediated by PA28 and hsp90 in Major Histocompatibility Complex Class I Antigen Processing

Major histocompatibility complex (MHC) class I ligands are mainly produced by the proteasome. Herein, we show that the processing of antigens is regulated by two distinct pathways, one requiring PA28 and the other hsp90. Both hsp90 and PA28 enhanced the antigen processing of ovalbumin (OVA). Geldanamycin, an inhibitor of hsp90, almost completely suppressed OVA antigen presentation in PA28α−/−/β−/− lipopolysaccharide blasts, but not in wild-type cells, indicating that hsp90 compensates for the loss of PA28 and is essential in the PA28-independent pathway. In contrast, treatment of cells with interferon (IFN)-γ, which induces PA28 expression, abrogated the requirement of hsp90, suggesting that IFN-γ enhances the PA28-dependent pathway, whereas it diminishes hsp90-dependent pathway. Importantly, IFN-γ did not induce MHC class I expressions in PA28-deficient cells, indicating a prominent role for PA28 in IFN-γ–stimulated peptide supply. Thus, these two pathways operate either redundantly or specifically, depending on antigen species and cell type

In vitro apatite formation and drug loading/release of porous TiO2 microspheres prepared by sol-gel processing with different SiO2 nanoparticle contents

Bioactive titania (TiO2) microparticles can be used as drug-releasing cement fillers for the chemotherapeutic treatment of metastatic bone tumors. Porous anatase-type TiO2 microspheres around 15 μm in diameter were obtained through a sol–gel process involving a water-in-oil emulsion with 30:70 SiO2/H2O weight ratio and subsequent NaOH solution treatment. The water phase consisted of methanol, titanium tetraisopropoxide, diethanolamine, SiO2 nanoparticles, and H2O, while the oil phase consisted of kerosene, Span 80, and Span 60. The resulting microspheres had a high specific surface area of 111.7 m2·g− 1. Apatite with a network-like surface structure formed on the surface of the microspheres within 8 days in simulated body fluid. The good apatite-forming ability of the microspheres is attributed to their porous structure and the negative zeta potential of TiO2. The release of rhodamine B, a model for a hydrophilic drug, was rapid for the first 6 h of soaking, but diffusion-controlled thereafter. The burst release in the first 6 h is problematic for clinical applications; nonetheless, the present results highlight the potential of porous TiO2 microspheres as drug-releasing cement fillers able to form apatite

In vitro apatite formation and drug loading/release of porous TiO2 microspheres prepared by sol-gel processing with different SiO2 nanoparticle contents

Bioactive titania (TiO2) microparticles can be used as drug-releasing cement fillers for the chemotherapeutic treatment of metastatic bone tumors. Porous anatase-type TiO2 microspheres around 15 μm in diameter were obtained through a sol–gel process involving a water-in-oil emulsion with 30:70 SiO2/H2O weight ratio and subsequent NaOH solution treatment. The water phase consisted of methanol, titanium tetraisopropoxide, diethanolamine, SiO2 nanoparticles, and H2O, while the oil phase consisted of kerosene, Span 80, and Span 60. The resulting microspheres had a high specific surface area of 111.7 m2·g− 1. Apatite with a network-like surface structure formed on the surface of the microspheres within 8 days in simulated body fluid. The good apatite-forming ability of the microspheres is attributed to their porous structure and the negative zeta potential of TiO2. The release of rhodamine B, a model for a hydrophilic drug, was rapid for the first 6 h of soaking, but diffusion-controlled thereafter. The burst release in the first 6 h is problematic for clinical applications; nonetheless, the present results highlight the potential of porous TiO2 microspheres as drug-releasing cement fillers able to form apatite

Comparison of Conventional 2D CC (Cranio-Caudal) + MLO (Medio-Lateral Oblique) Bi-Directional Photography and 2D-MLO + DBT-MLO (Digital Breast Tomosynthesis) in Mammography Examination

Introduction: Mammography (MMG) is an excellent examination for breast cancer detection and is widely used in both screening and clinical practice. However, the breast thickness and background the concentration of the mammary gland is large among individuals, and the mammary gland and cancer may overlap and it may not be possible to point out a lesion. In recent years, digital breast tomosynthesis (hereinafter referred to as DBT) has been introduced to solve these problems, and its usefulness has been reported in clinical practice. Therefore, in anticipation of a higher cancer detection rate etc., we compared the conventional 2D CC + MLO 2-way MMG examination with 2DMLO + DBTMLO 2-way MMG examination.Materials and Methods: The combination of 2D CC + MLO and 2DMLO + DBTMLO was read for 95 cases of breast cancer taking 2D CC and MLO and DBT MLO from May 2016 to October 2017. It was judged that the category 3 or more required detailed examination, cancer detection, and cancer detection rates were compared. Subjects were 28 to 87 years of age (median: 55 years), breast composition: high concentration 15.8% (15 cases), heterogeneous high concentration 47.4% (45 cases), mammary gland 28.4% (27 cases), Fatty was 8.4% (8 cases).Results: The cancer detection rate was 87% for the 2D CC + MLO combination and 94% for the 2DMLO + DBTMLO combination in 95 cases of breast cancer. The interpretation time was 95 minutes for the 2D CC + MLO combination and 110 minutes for the 2DMLO + DBTMLO combination.The breast cancer detected only by the combination of 2D CC + MLO was scattered in 1 case and was classified as Category 3 by FAD. Breast cancer detected only by the combination of 2DMLO + DBTMLO: 8 cases with uneven distribution of breast composition, 3 cases with scattered mammary gland, 3 cases with 5 cases with disordered construction, Category 4 with 3 cases with FAD was.Conclusion: Both 2D CC + MLO combination and 2DMLO + DBTMLO combination are considered useful for screening MMG examination. In particular, we would like to consider the introduction to medical examinations for the addition of MMG in DBT, but the issue of the amount of image information, the problem of exposure to radiation, the direction of imaging, the establishment of interpretation methods etc. are future issues

Distinction of synthetic dl-α-tocopherol from natural vitamin E (d-α-tocopherol) by reversed-phase liquid chromatography. Enhanced selectivity of a polymeric C18 stationary phase at low temperature and/or at high pressure

© 2016 Elsevier B.V. Separation of diastereomers of DL-α-tocopherol was studied by reversed-phase liquid chromatography using three types of stationary phases, polymeric ODS, polymeric C30, and monomeric ODS. Polymeric ODS stationary phase (Inertsil ODS-P, 3 mmID, 20 cm) was effective for the separation of the isomers created by the presence of three chiral centers on the alkyl chain of synthetic DL-α-tocopherol. Considerable improvement of the separation of isomers was observed on ODS-P phase at high pressure and at low temperature. Complete separation of four pairs of diastereomers was achieved at 12.0 °C, 536 bar, while three peaks were observed when the separation was carried out either at 12.0 °C at low pressure or at 20 °C at 488 bar. Higher temperature (30.0 °C) with the ODS-P phase resulted in only partial separation of the diastereomers even at high pressure. Only slight resolution was observed for the mixture of diastereomers with the C30 stationary phase (Inertsil C30) at 12.0 °C and 441 bar, although the stationary phase afforded greater resolution for β- and γ-tocopherol than ODS-P. A monomeric C18 stationary phase did not show any separation at 12.0 °C and 463 bar. The results suggest that the binding site of the polymeric ODS-P phase is selective for flexible alkyl chains that provided the longest retention for the natural form, (R,R,R) form, and the enantiomer, (S,S,S) form, of DL-α-tocopherol

α-Selective glycosidation of d-tagatofuranose with a 3,4-O-isopropylidene protection

An α-selective glycosidation reaction of D-tagatofuranose was successfully achieved using 3,4-O-isopropylidene-protected D-tagatofuranose as a glycosyl donor. A variety of glycosyl acceptors, including primary, secondary, and β-amino alcohols, and carbohydrates, can be used for this D-tagatofuranosidation reaction with complete α-selectivities and good yields (57-83%). The stereochemistries at the anomeric positions were determined by nuclear Overhauser effect spectroscopic correlations, as well as comparison of the chemical shifts in the 13C NMR spectra

Population-level transition of capsular polysaccharide types among sequence type 1 group B Streptococcus isolates with reduced penicillin susceptibility during a long-term hospital epidemic

Over a 35-month period, group B Streptococcus isolates with reduced penicillin susceptibility (PRGBS) were detected from elderly patients at a regional hospital in Japan, accompanying population-level transition of PRGBS serotypes. The genetic relatedness of 77 non-duplicate PRGBS from 73 patients was analysed. Serotype III PRGBS predominated (16 serotype III/1 serotype Ib) in the first 9 months (period I), then 3 serotype Ib isolates appeared transiently for the next 3 months (period II), which was replaced predominantly by serotype Ia (20 serotype Ia/1 serotype III/1 non-typeable) for 9 months (period III). In the last 14 months (period IV), besides 25 serotype Ia isolates, 10 serotype III were also identified. Serotypes III and Ia isolates, belonging to ST1, shared G329V, G398A, V405A and G429D substitutions in penicillin-binding protein 2X. Of three strains subjected to whole-genome sequencing, serotype III strain SU12 (period I) had a higher degree of genomic similarity with serotype Ia strain SU97 (period III) than serotype Ib strain SU67 (period II) based on average nucleotide identity and single nucleotide polymorphisms. Analysis of the cps gene clusters and the upstream and downstream flanking sequences revealed that disruption of the hyaluronidase gene located upstream of cpsY by insertion of IS 1548 was found in strain SU12, whereas Delta ISSag8 was inserted between tRNA-Arg and rpsA genes located downstream of cpsL in strain SU97. Interestingly, most serotype III PRGBS re-emerging in period IV had this tRNA-Arg-Delta ISSag8-rpsA region. Capsular switching and nosocomial transmission may possibly contribute to population-level serotype replacement among ST1 PRGBS isolates. (c) 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.ArticleINTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS.53(3):203-210(2019)journal articl

Stereoselective synthesis of (+)-5-thiosucrose and (+)-5-thioisosucrose

+)-5-Thiosucrose 1, a novel isosteric sulfur analog of sucrose, was synthesized stereoselectively for the first time via indirect β-d-fructofuranosidation involving selective β-d-psicofuranosidation, followed by stereo-inversion of the secondary hydroxy group at the C-3 position on the furanose ring. Glycosidation of protected 5-Thio-d-glucose with a d-psicofuranosyl donor provided β-d-psicofuranosyl 5-Thio-α-d-glucopyranoside and that with d-fructofuranosyl donor gave α-d-fructofuranosyl 5-Thio-α-d-glucopyranoside. Two anomeric stereocenters of the glycosyl donor and acceptor were controlled correctly to provide a single disaccharide among four possible anomeric isomers in the glycosylation. Conversion of the resulting disaccharides afforded (+)-5-Thiosucrose 1 and (+)-5-Thioisosucrose 2 in excellent yields, respectively. Inhibitory activities of 1 and 2 against α-glucosidase in vitro were also examined

Atypical gaze patterns in children and adults with autism spectrum disorders dissociated from developmental changes in gaze behaviour

Eye tracking has been used to investigate gaze behaviours in individuals with autism spectrum disorder (ASD). However, traditional analysis has yet to find behavioural characteristics shared by both children and adults with ASD. To distinguish core ASD gaze behaviours from those that change with development, we examined temporo-spatial gaze patterns in children and adults with and without ASD while they viewed video clips. We summarized the gaze patterns of 104 participants using multidimensional scaling so that participants with similar gaze patterns would cluster together in a two-dimensional plane. Control participants clustered in the centre, reflecting a standard gaze behaviour, whereas participants with ASD were distributed around the periphery. Moreover, children and adults were separated on the plane, thereby showing a clear effect of development on gaze behaviours. Post hoc frame-by-frame analyses revealed the following findings: (i) both ASD groups shifted their gaze away from a speaker earlier than the control groups; (ii) both ASD groups showed a particular preference for letters; and (iii) typical infants preferred to watch the mouth rather than the eyes during speech, a preference that reversed with development. These results highlight the importance of taking the effect of development into account when addressing gaze behaviours characteristic of ASD