CD4
+
T cells that recognize antigenic peptides presented on HLA class II are essential for inducing an optimal anti-tumor immune response, and adoptive transfer of tumor antigen-specific ...TCR-transduced CD4
+
T cells with high responsiveness against tumor is a promising strategy for cancer treatment. Whereas a precise evaluation method of functional avidity, an indicator of T cell responsiveness against tumors, has been established for HLA class I-restricted TCRs, it remains unestablished for HLA class II-restricted TCRs. In this study, we generated a novel platform cell line, CD4-2D3, in which GFP reporter was expressed by NFAT activation via TCR signaling, for correctly evaluating functional avidity of HLA class II-restricted TCRs. Furthermore, using this platform cell line, we succeeded in maturating functional avidity of an HLA class II-restricted TCR specific for a WT1-derived helper peptide by substituting amino acids in complementarity determining region 3 (CDR3) of the TCR. Importantly, we demonstrated that transduction of an avidity-maturated TCR conferred strong cytotoxicity against WT1-expressing leukemia cells on CD4
+
T cells, compared to that of its original TCR. Thus, CD4-2D3 cell line should be useful not only to evaluate TCR functional avidity in HLA class II-restricted TCRs but also to screen appropriate TCRs for clinical applications such as cancer immunotherapy.
With the increase in scale and the division of labor in the dairy industry in Japan, the use of liquid digestate derived from livestock manure produced in biogas plants as fertilizer has been ...promoted. It is a challenge to optimize the location, timing, and amount of application of the digestate to pastures. Here, we developed a Web-based system to manage the application of liquid digestate fertilizer to multiple paddocks on the basis of application history. It uses an existing cloud-based system to collect and manage application history data and open satellite imagery data to calculate the Enhanced Vegetation Index of pastures, which is used to evaluate their growth in relation to the amount of digestate applied per year. By comparison with the annual average value in the district, paddocks with excess nutrient application (more digestate application but poorer grass growth) are selected as “caution” areas and are mapped in the Web application. Users can select a paddock and view its history of digestate application and grass growth. Through this system, we aim to encourage information sharing and understanding among farmers, those who manage and apply liquid digestate, and local government officials, with the goal of more efficient use of local resources.
Game genres, availability on smartphones, in-game purchases, and playing duration, have been thought to influence Gaming Disorder (GD). However, little research has comprehensively examined their ...relationships with GD. Therefore, we examined the relationship between GD, in-game purchases, gaming duration via consoles and smartphones, and genres of smartphone games. Study 1 was based on self-reports, and Study 2 included objective data to clarify these associations.
We conducted two independent online surveys that collected sociodemographic data, game use patterns, and psychopathological assessment data, including GD severity (Study 1: N = 32,690; Study 2: N = 3,163). General mental illness scores and objective gaming time were also collected in Study 2.
In Study 1, in-game purchases, several gaming genres, and subjective gaming duration were positively associated with probable GD. On the other hand, interactions between card games and loot box charges were negatively related to probable GD. In Study 2, objective gaming times of most game genres were not associated with GD. Although the correlation between subjective and objective gaming duration was moderate, their correlations with GD differed.
These results suggest the complexity of relationships between GD and in-game purchases, genres, and gaming duration. Results of this study suggest the importance of proper assessment of GD reflecting actual functional impairment in social life. Future studies should improve and update evaluation of assessments for gaming.
Abstract
The molecular pathophysiology underlying lumbar spondylosis development remains unclear. To identify genetic factors associated with lumbar spondylosis, we conducted a genome-wide ...association study using 83 severe lumbar spondylosis cases and 182 healthy controls and identified 65 candidate disease-associated single nucleotide polymorphisms (SNPs). Replication analysis in 510 case and 911 control subjects from five independent Japanese cohorts identified rs2054564, located in intron 7 of
ADAMTS17
, as a disease-associated SNP with a genome-wide significance threshold (P = 1.17 × 10
–11
, odds ratio = 1.92). This association was significant even after adjustment of age, sex, and body mass index (P = 7.52 × 10
–11
). A replication study in a Korean cohort, including 123 case and 319 control subjects, also verified the significant association of this SNP with severe lumbar spondylosis. Immunohistochemistry revealed that fibrillin-1 (FBN1) and ADAMTS17 were co-expressed in the annulus fibrosus of intervertebral discs (IVDs). ADAMTS17 overexpression in MG63 cells promoted extracellular microfibrils biogenesis, suggesting the potential role of ADAMTS17 in IVD function through interaction with fibrillin fibers. Finally, we provided evidence of FBN1 involvement in IVD function by showing that lumbar IVDs in patients with Marfan syndrome, caused by heterozygous
FBN1
gene mutation, were significantly more degenerated. We identified a common SNP variant, located in
ADAMTS17
, associated with susceptibility to lumbar spondylosis and demonstrated the potential role of the ADAMTS17-fibrillin network in IVDs in lumbar spondylosis development.
Here we report the largest Asian genome-wide association study (GWAS) for systemic sclerosis performed to date, based on data from Japanese subjects and comprising of 1428 cases and 112,599 controls. ...The lead SNP is in the FCGR/FCRL region, which shows a penetrating association in the Asian population, while a complete linkage disequilibrium SNP, rs10917688, is found in a cis-regulatory element for IRF8. IRF8 is also a significant locus in European GWAS for systemic sclerosis, but rs10917688 only shows an association in the presence of the risk allele of IRF8 in the Japanese population. Further analysis shows that rs10917688 is marked with H3K4me1 in primary B cells. A meta-analysis with a European GWAS detects 30 additional significant loci. Polygenic risk scores constructed with the effect sizes of the meta-analysis suggest the potential portability of genetic associations beyond populations. Prioritizing the top 5% of SNPs of IRF8 binding sites in B cells improves the fitting of the polygenic risk scores, underscoring the roles of B cells and IRF8 in the development of systemic sclerosis. The results also suggest that systemic sclerosis shares a common genetic architecture across populations.
β-D-galactofuranose (Galf) is a component of polysaccharides and glycoconjugates and its transferase has been well analyzed. However, no β-D-galactofuranosidase (Galf-ase) gene has been identified in ...any organism. To search for a Galf-ase gene we screened soil samples and discovered a strain, identified as a Streptomyces species by the 16S ribosomal RNA gene analysis, that exhibits Galf-ase activity for 4-nitrophenyl β-D-galactofuranoside (pNP-β-D-Galf) in culture supernatants. By draft genome sequencing of the strain, named JHA19, we found four candidate genes encoding Galf-ases. Using recombinant proteins expressed in Escherichia coli, we found that three out of four candidates displayed the activity of not only Galf-ase but also α-L-arabinofuranosidase (Araf-ase), whereas the other one showed only the Galf-ase activity. This novel Galf-specific hydrolase is encoded by ORF1110 and has an optimum pH of 5.5 and a Km of 4.4 mM for the substrate pNP-β-D-Galf. In addition, this enzyme was able to release galactose residue from galactomannan prepared from the filamentous fungus Aspergillus fumigatus, suggesting that natural polysaccharides could be also substrates. By the BLAST search using the amino acid sequence of ORF1110 Galf-ase, we found that there are homolog genes in both prokaryotes and eukaryotes, indicating that Galf-specific Galf-ases widely exist in microorganisms.
The wild‐type Wilms’ tumor gene WT1 is overexpressed in human primary leukemia and in a wide variety of solid cancers. All of the four WT1 isoforms are expressed in primary cancers and each is ...considered to have a different function. However, the functions of each of the WT1 isoforms in cancer cells remain unclear. The present study demonstrated that constitutive expression of the WT1 17AA(–)/KTS(–) isoform induces morphological changes characterized by a small‐sized cell shape in TYK‐nu.CP‐r (TYK) ovarian cancer cells. In the WT1 17AA(–)/KTS(–) isoform‐transduced TYK cells, cell–substratum adhesion was suppressed, and cell migration and in vitro invasion were enhanced compared to that in mock vector‐transduced TYK cells. Constitutive expression of the WT1 17AA(–)/KTS(–) isoform also induced morphological changes in five (one gastric, one esophageal, two breast and one fibrosarcoma) of eight cancer cell lines examined. No WT1 isoforms other than the WT1 17AA(–)/KTS(–) isoform induced the phenotypic changes. A decrease in α‐actinin 1 and cofilin expression and an increase in gelsolin expression were observed in WT1 17AA(–)/KTS(–) isoform‐transduced TYK cells. In contrast, co‐expression of α‐actinin 1 and cofilin or knockdown of gelsolin expression by small interfering RNA restored WT1 17AA(–)/KTS(–) isoform‐transduced TYK cells to a phenotype that was comparable to that of the parent TYK cells. These results indicated that the WT1 17AA(–)/KTS(–) isoform exerted its oncogenic functions through modulation of cytoskeletal dynamics. The present results may provide a novel insight into the signaling pathway of the WT1 gene for its oncogenic functions. (Cancer Sci 2006; 97: 259–270)
The short version of the smartphone addiction scale (SAS-SV) is widely used to measure problematic smartphone use (PSU). This study examined the validity and reliability of the SAS-SV among Japanese ...adults, as well as cross-sectional and longitudinal associations with relevant mental health traits and problems.
Datasets from a larger project on smartphone use and mental health were used to conduct two studies. Participants were adults aged over 20 years who carried a smartphone.
Study 1 (n = 99,156) showed the acceptable internal consistency and structural validity of the SAS-SV with a bifactor model with three factors. For the test-retest reliability of the SAS-SV, the intraclass correlation coefficient (ICC) was .70, 95% CI .69, 70, when the SAS-SV was measured seven and twelve months apart (n = 20,389). Study 2 (n = 3419) revealed that when measured concurrently, the SAS-SV was strongly positively correlated with another measure of PSU and moderately correlated with smartphone use time, problematic internet use (PIU), depression, the attentional factor of impulsiveness, and symptoms related to attention-deficit hyperactivity disorder and obsessive-compulsive disorder. When measured 12 months apart, the SAS-SV was positively strongly associated with another measure of PSU and PIU and moderately associated with depression.
The structural validity of the SAS-SV appeared acceptable among Japanese adults with the bifactor model. The reliability of the SAS-SV was demonstrated in the subsequent seven- and twelve-month associations.
The cross-sectional and longitudinal associations of the SAS-SV provided further evidence regarding PSU characteristics.
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