Chicken CD1 genes are located in the MHC: CD1 and endothelial protein C receptor genes constitute a distinct subfamily of class-I-like genes that predates the emergence of mammals

Mammals have several major histocompatibility complex (MHC) class-I-like genes. Although some of them are assumed to have originated before the emergence of mammals, the origin of class-I-like genes is poorly understood. We analyzed here the recently released chicken draft genome sequence and identified two families of class-I-like genes: CD1 and PROCR (the gene for the endothelial protein C receptor). Chickens have two CD1 genes, designated CD1.1 and CD1.2, located in tandem ∼840 bp apart from each other. Chicken CD1.1 and CD1.2 are neither group 1- nor group 2-like, indicating that the two groups of CD1 emerged in a mammalian lineage. Although the database provides no information as to their chromosomal localization, we found that chicken CD1 genes are located adjacent to the previously characterized MHC B system contig on chromosome 16. We confirmed the linkage of CD1 to the B system by dual-color fluorescence in situ hybridization. Chickens have a single copy of PROCR. Among known class-I-like genes, PROCR is most closely related to CD1, indicating that CD1 and PROCR constitute a distinct subfamily of class-I-like genes that predates the emergence of mammals

Construction and Use Examples of Private Electronic Notary Service in Educational Institutions

People have many documents. For example, a variety of documents are prepared and used in public institutions. As the internet becomes widely available in recent years, paper documents are being replaced with electronic data, which are often distributed in the form of electronic data without being printed out. Similarly, in educational institutions, increasing number of documents are distributed in the form of electronic data. Such data are distributed through various routes and means, and prone to the risk of alteration in the process. Data may be protected against alteration, but it is difficult to completely prevent data alteration in the distribution process. Data can be generated with electronic signature that allows for the identification of data creator and possible alterations by third parties. This method is, however, not valid if the data becomes separated from the electronic signature, making the validation of data creator or data alterations difficult or impossible. In this paper, we describe the invention of a system that, even in cases where data is separated form the electronic signature, enables easy identification of possible data alterations by the electronic signature management. And we describe here an exploratory construction of private electronic notary service in university. We also add a review on the utilization method of private electronic notary service in universities

Construction and Use Examples of Private Electronic Notary Service in Educational Institutions

People have many documents. For example, a variety of documents are prepared and used in public institutions. As the internet becomes widely available in recent years, paper documents are being replaced with electronic data, which are often distributed in the form of electronic data without being printed out. Similarly, in educational institutions, increasing number of documents are distributed in the form of electronic data. Such data are distributed through various routes and means, and prone to the risk of alteration in the process. Data may be protected against alteration, but it is difficult to completely prevent data alteration in the distribution process. Data can be generated with electronic signature that allows for the identification of data creator and possible alterations by third parties. This method is, however, not valid if the data becomes separated from the electronic signature, making the validation of data creator or data alterations difficult or impossible. In this paper, we describe the invention of a system that, even in cases where data is separated form the electronic signature, enables easy identification of possible data alterations by the electronic signature management. And we describe here an exploratory construction of private electronic notary service in university. We also add a review on the utilization method of private electronic notary service in universities

Serial Assessment of Immune Status by Circulating CD8+ Effector T Cell Frequencies for Posttransplant Infectious Complications

To clarify the role of CD8+ effector T cells for infectious complications, 92 recipients were classified according to the hierarchical clustering of preoperative CD8+CD45 isoforms: Group I was naive, Group II was effector memory, and Group III was effector (E) T cell-dominant. The posttransplant infection rates progressively increased from 29% in Group I to 64.3% in Group III recipients. The posttransplant immune status was compared with the pretransplant status, based on the measure (% difference) and its graphical form (scatter plot). In Groups I and II, both approaches showed a strong upward deviation from pretransplant status upon posttransplant infection, indicating an enhanced clearance of pathogens. In Group III, in contrast, both approaches showed a clear downward deviation from preoperative status, indicating deficient cytotoxicity. The % E difference and scatter plot can be used as a useful indicator of a posttransplant infectious complication

Anti-oxidative Amino Acid L-ergothioneine Modulates the Tumor Microenvironment to Facilitate Adjuvant Vaccine Immunotherapy

Cancer vaccines consist of a tumor-associated antigen (TAA) and adjuvant. These vaccines induce and activate proliferation of TAA-specific cytotoxic T lymphocytes (CTLs), suppressing tumor growth. The therapeutic efficacy of TAA-specific CTLs depends on the properties of tumor microenvironment. The environments make immunosuppressive by function of regulatory T cells and tumor-associated myeloid cells; thus, regulation of these cells is important for successful cancer immunotherapy. We report here that L-ergothioneine (EGT) with the adjuvant Toll-like receptor 2 (TLR2) ligand modulated suppressive microenvironments to be immune-enhancing. EGT did not augment DC-mediated CTL priming or affect CTL activation in draining lymph node and spleen. However, EGT decreased the immuno-suppressive function of tumor-associated macrophages (TAMs). TLR2 stimulation accompanied with EGT administration downregulated expression of PD-L1, CSF-1R, arginase-1, FAS ligand, and TRAIL in TAMs, reflecting reduction of CTL suppression. An anti-oxidative thiol-thione residue of EGT was essential to dampening CTL suppression. The effect was specific to the thiol-thione residue of EGT because no effect was observed with another anti-oxidant N-acetyl-L-cysteine (NAC). A CTL-suppressive environment made by TLR2 is relieved to be improved by the addition of EGT, which may ameliorate the efficacy of vaccine immunotherapy

Copper Deficiency Induced Emphysema Is Associated with Focal Adhesion Kinase Inactivation

Background: Copper is an important regulator of hypoxia inducible factor 1 alpha (HIF-1a) dependent vascular endothelial growth factor (VEGF) expression, and is also required for the activity of lysyl oxidase (LOX) to effect matrix protein crosslinking. Cell detachment from the extracellular matrix can induce apoptosis (anoikis) via inactivation of focal adhesion kinase (FAK). Methodology: To examine the molecular mechanisms whereby copper depletion causes the destruction of the normal alveolar architecture via anoikis, Male Sprague-Dawley rats were fed a copper deficient diet for 6 weeks while being treated with the copper chelator, tetrathiomolybdate. Other groups of rats were treated with the inhibitor of auto-phosphorylation of FAK, 1,2,4,5-benzenetetraamine tetrahydrochloride (1,2,4,5-BT) or FAK small interfering RNA (siRNA). Principal Findings: Copper depletion caused emphysematous changes, decreased HIF-1a activity, and downregulated VEGF expression in the rat lungs. Cleaved caspase-3, caspase-8 and Bcl-2 interacting mediator of cell death (Bim) expression was increased, and the phosphorylation of FAK was decreased in copper depleted rat lungs. Administration of 1,2,4,5-BT and FAK siRNA caused emphysematous lung destruction associated with increased expression of cleaved capase-3, caspase-8 and Bim. Conclusions: These data indicate that copper-dependent mechanisms contribute to the pathogenesis of emphysema

A human PSMB11 variant affects thymoproteasome processing and CD8+ T cell production

The Psmb11-encoded β5t subunit of the thymoproteasome, which is specifically expressed in cortical thymic epithelial cells (cTECs), is essential for the optimal positive selection of functionally competent CD8+ T cells in mice. Here, we report that a human genomic PSMB11 variation, which is detectable at an appreciable allele frequency in human populations, alters the β5t amino acid sequence that affects the processing of catalytically active β5t proteins. The introduction of this variation in the mouse genome revealed that the heterozygotes showed reduced β5t expression in cTECs and the homozygotes further exhibited reduction in the cellularity of CD8+ T cells. No severe health problems were noticed in many heterozygous and 5 homozygous human individuals. Long-term analysis of health status, particularly in the homozygotes, is expected to improve our understanding of the role of the thymoproteasome-dependent positive selection of CD8+ T cells in humans

Prevention of hypoglycemia by intermittent-scanning continuous glucose monitoring device combined with structured education in patients with type 1 diabetes mellitus : A randomized, crossover trial

Aims: We conducted a randomized, crossover trial to compare intermittent-scanning continuous glucose monitoring (isCGM) device with structured education (Intervention) to self-monitoring of blood glucose (SMBG) (Control) in the reduction of time below range. Methods: This crossover trial involved 104 adults with type 1 diabetes mellitus (T1DM) using multiple daily injections. Participants were randomly allocated to either sequence Intervention/Control or sequence Control/Intervention. During the Intervention period which lasted 84 days, participants used the first-generation FreeStyle Libre (Abbott Diabetes Care, Alameda, CA, USA) and received structured education on how to prevent hypoglycemia based on the trend arrow and by frequent sensor scanning (≥10 times a day). Confirmatory SMBG was conducted before dosing insulin. The Control period lasted 84 days. The primary endpoint was the decrease in the time below range (TBR; <70 mg/dL). Results: The time below range was significantly reduced in the Intervention arm compared to the Control arm (2.42 ± 1.68 h/day [10.1 %±7.0 %] vs 3.10 ± 2.28 h/day [12.9 %±9.5 %], P = 0.012). The ratio of high-risk participants with low blood glucose index >5 was significantly reduced (8.6 % vs 23.7 %, P < 0.001). Conclusions: The use of isCGM combined with structured education significantly reduced the time below range in patients with T1DM