Grit and Work Engagement: A Cross-Sectional Study

Grit, defined as perseverance of effort and consistency of interest, has attracted attention as a predictor of success in various fields beyond IQ and the Big Five personality dimension of Conscientiousness. The purpose of the current study was to examine previously uninvestigated questions regarding grit using a cross-sectional design among a large number of working adults in Japan. First, we tested geographical generalizability of associations between grit and orientations towards happiness by comparing previous studies in the U.S. and the current study in Japan. It was confirmed that orientation towards meaning rather than orientation towards engagement had a stronger positive correlation with grit in our sample of Japanese people. This result is inconsistent with previous studies in the U.S. Furthermore, the Big Five dimension of Openness to Experience was newly confirmed as having a positive association with grit. Second, we examined the association between grit and work engagement, which is considered as an outcome indicator for work performance. In this analysis, grit was a strong predictor for work performance as well as academic performance.     

Malectin Forms a Complex with Ribophorin I for Enhanced Association with Misfolded Glycoproteins

Malectin is an endoplasmic reticulum-resident lectin, which recognizes di-glucosylated Glc₂Man₉GlcNAc₂ (G2M9) N-glycans on newly synthesized glycoproteins. We previously demonstrated that malectin preferentially associates with misfolded glycoproteins and inhibits their secretion (Chen, Y., Hu, D., Yabe, R., Tateno, H., Qin, S. Y., Matsumoto, N., Hirabayashi, J., and Yamamoto, K. (2011) Mol. Biol. Cell 22, 3559–3570). The sugar binding activity of malectin is required for this process. However, because G2M9 N-glycans are generated at the very early stage of processing and are typically found on both misfolded glycoproteins and glycoproteins undergoing folding, other mechanisms must underlie the preference of malectin for misfolded glycoproteins. Here, we searched for proteins that were co-immunoprecipitated with malectin, and we found that malectin formed a stable complex with an endoplasmic reticulum-resident transmembrane protein, ribophorin I. Co-expression of malectin and ribophorin I significantly enhanced the association between malectin and a folding-defective α1-antitrypsin variant (null Hong Kong) and reduced its secretion; however, secretion of wild-type α1-antitrypsin was not affected. The enhanced association and reduced secretion were counteracted by siRNA-mediated down-regulation of ribophorin I. Also, a reporter assay revealed that ribophorin I preferentially interacted with misfolded ribonuclease A but not with the native form, suggesting that ribophorin I may function as a chaperone that recognizes misfolded proteins inside cells. These results provide the first evidence of the mechanism by which malectin preferentially associates with misfolded glycoproteins.     

Histology and tetracycline labeling of a single section of alveolar bone of first molars in the rat

We observed the histology and tetracycline (TC) labeling in a single frontal section of alveolar bone of upper first molars of adolescent rats. A single injection of TC was administered intraperitonealy in adolescent rats. After three weeks, the upper jaws were immersed rapidly in liquid nitrogen and sectioned. Five micrometer unfixed, undecalcified frozen sections were cut and observed by light and fluorescence microscopy. Frontal sections of the upper first molar area revealed that the structural relationships among the roots, the periodontal ligament and the alveolar bone, and also between the cervical enamel and the attachment epithelium were well preserved. The TC labeling lines in the sections were very clear and distinguished new bone from old bone. The brightness of the lines differed among regions. An analysis of the brightness in the same section suggested a difference in the bone forming activity at the time of injection.     

Autophagy Creates a CTL Epitope That Mimics Tumor-Associated Antigens

The detailed mechanisms responsible for processing tumor-associated antigens and presenting them to CTLs remain to be fully elucidated. In this study, we demonstrate a unique CTL epitope generated from the ubiquitous protein puromycin-sensitive aminopeptidase, which is presented via HLA-A24 on leukemic and pancreatic cancer cells but not on normal fibroblasts or EBV-transformed B lymphoblastoid cells. The generation of this epitope requires proteasomal digestion and transportation from the endoplasmic reticulum to the Golgi apparatus and is sensitive to chloroquine-induced inhibition of acidification inside the endosome/lysosome. Epitope liberation depends on constitutively active autophagy, as confirmed with immunocytochemistry for the autophagosome marker LC3 as well as RNA interference targeting two different autophagy-related genes. Therefore, ubiquitously expressed proteins may be sources of specific tumor-associated antigens when processed through a unique mechanism involving autophagy.     

Synthesis of N-Carbamyl-d-2-thienyl-glycine and d-2-Thienylglycine by Microbial Hydantoinase

A debranching enzyme purified from germinating rice endosperm hydrolyzed oligosaccharides having maltosyl or maltotriosyl branches (B₄-B₆) moderately. Hydrolysis of maltosylmaltose by a “pullulanase” of higher plant origin has been scarcely reported, while our enzyme debranched maltosylmaltose like microbial pullulanase. Additionally, the enzyme slowly hydrolyzed isopanose to glucose and maltose.

Gel-filtration analyses of hydrolysis products of polysaccharides with the enzyme suggested that while it hydrolyzed α-1,6-linkages of pullulan at random, it hydrolyzed amylopectin and glycogen at the outer α-1,6-linkages preferentially In the hydrolysis products of glycogen with the enzyme for a longer incubation time, large molecular-weight glucans still remained. This indicated that the enzyme was able to hydrolyze a few of the α-1,6-linkages of glycogen.     

Identification of 2-(2′-fluoro-[1,1′-biphenyl]-2-yl)acetamide as a Sodium Valproate-like broad spectrum anti-epileptic drug candidate

By further optimizing compound A [2′-fluoro-N-methyl-[1,1′-biphenyl]-2-sulfonamide], we identified DSP-0565 [2-(2′-fluoro-[1,1′-biphenyl]-2-yl)acetamide, 17a] as a strong, broad-spectrum anti-epileptic drug (AED) candidate. Our efforts mainly focused on finding an alternative polar group for the sulfonamide in order to improve ADME profile of compound A including good metabolic stability and no reactive metabolic production. This led to the identification of biphenyl acetamide as a new scaffold for development of broad-spectrum AED candidates. DSP-0565 showed anti-convulsant activity in various models (scPTZ, MES, 6?Hz and amygdala kindling) with good safety margin, and was therefore selected as a clinical candidate.     

Effect of Sugars and Sugar Analogs on Autoxidation of Methyl Linoleate and Safflower Oil

The antioxidative and prooxidative activities of sugars and sugar analogs were investigated on the autoxidation of methyl linoleate and safflower oil. Autoxidation of methyl linoleate was conducted in either the dry state or aqueous emulsion state. Although all sugars and sugar analogs inhibited the autoxidation of methyl linoleate in the dry system, the reducing sugars accelerated oxidation in the aqueous emulsion system. When glyceraldehyde, dihydroxyacetone and glycerol were added in the oxidation system, glyceraldehyde and dihydroxyacetone with water accelerated the formation and decomposition of methyl linoleate monohydroperoxide. On the other hand, glycerol inhibited the formation and decomposition of hydroperoxide. These results indicate that the carbonyl group of sugars accelerates lipid peroxidation and the hydroxy group of sugars and sugar analogs inhibits the oxidation. The effect of sugars in the safflower oil-sugar-cellulose oxidation system was also examined. Sugars at low humidity inhibited the autoxidation of safflower oil, but reducing sugars at high humidity accelerated the oxidation.     

Studies on the Host-Specific Pathotoxins Produced by Helminthosporium maydis,race T

Two host-specific pathotoxins, Band 1- and Band 2-toxins, were isolated from the toxin complex obtained from the culture broth and mycelial mat of Helminthosporium maydis, race T, the fungus causing Southern corn blight disease. Chemical and spectrometric studies showed them to be polyketo-polyhydroxy compounds with C₄₁ carbon chains. Band 2-toxin is identical to Band 1-toxin except that Band 2 toxin has an additional hydroxyl group in place of one of the keto-group of Band 1-toxin.     

Detection of Peramivir and Laninamivir,New Anti-Influenza Drugs,in Sewage Effluent and River Waters in Japan

This is the first report of the detection of two new anti-influenza drugs, peramivir (PER) and laninamivir (LAN), in Japanese sewage effluent and river waters. Over about 1 year from October 2013 to July 2014, including the influenza prevalence season in January and February 2014, we monitored for five anti-influenza drugs—oseltamivir (OS), oseltamivir carboxylate (OC), zanamivir (ZAN), PER, and LAN—in river waters and in sewage effluent flowing into urban rivers of the Yodo River system in Japan. The dynamic profiles of these anti-influenza drugs were synchronized well with that of the numbers of influenza patients treated with the drugs. The highest levels in sewage effluents and river waters were, respectively, 82 and 41 ng/L (OS), 347 and 125 ng/L (OC), 110 and 35 ng/L (ZAN), 64 and 11 ng/L (PER), and 21 and 9 ng/L (LAN). However, application of ozone treatment before discharge from sewage treatment plants was effective in reducing the levels of these anti-influenza drugs in effluent. The effectiveness of the ozone treatment and the drug dependent difference in susceptibility against ozone were further evidenced by ozonation of a STP effluent in a batch reactor. These findings should help to promote further environmental risk assessment of the generation of drug-resistant influenza viruses in aquatic environments.