87 research outputs found
Dual tyrosine kinase inhibitor for focal adhesion kinase and insulin-like growth factor-I receptor exhibits an anticancer effect in esophageal adenocarcinoma in vitro and in vivo
Quality of life of children with neurodevelopmental disorders and their parents during the COVID-19 pandemic : a 1-year follow-up study
This study aimed to reveal changes in the quality of life (QOL) of children with neurodevelopmental disorders and their parents, and the interaction between their QOL and parental mental state during the coronavirus 2019 (COVID-19) pandemic. Eighty-nine school-aged children and parents participated in surveys in May 2020 (T1) and May 2021 (T2). The parents completed questionnaires that assessed their QOL, depression, parenting stress, and living conditions. Children's temporary mood status was evaluated using the self-reported visual analog scale (VAS). Children's QOL and VAS at T2 were higher than their QOL at T1. Parents' QOL at T2 was lower than their QOL at T1. Severe parental depression at T1 had a synergistic effect on severe parenting stress and severe depressive state at T2. Additionally, children's high QOL at T1 had a synergistic effect on low parenting stress and children's high QOL at T2. Furthermore, children's low VAS scores and parents' low QOL at T2 were associated with deterioration of family economic status. Children and parents' QOL changed during the prolonged COVID-19 pandemic. Improvement in children's QOL was influenced by reduced maternal depressive symptoms. Public support for parental mental health is important to avoid decreasing QOL.Peer reviewe
Criterion and Construct Validity of the CogState Schizophrenia Battery in Japanese Patients with Schizophrenia
BACKGROUND: The CogState Schizophrenia Battery (CSB), a computerized cognitive battery, covers all the same cognitive domains as the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery but is briefer to conduct. The aim of the present study was to evaluate the criterion and construct validity of the Japanese language version of the CSB (CSB-J) in Japanese patients with schizophrenia. METHODOLOGY/PRINCIPAL FINDINGS: Forty Japanese patients with schizophrenia and 40 Japanese healthy controls with matching age, gender, and premorbid intelligence quotient were enrolled. The CSB-J and the Brief Assessment of Cognition in Schizophrenia, Japanese-language version (BACS-J) were performed once. The structure of the CSB-J was also evaluated by a factor analysis. Similar to the BACS-J, the CSB-J was sensitive to cognitive impairment in Japanese patients with schizophrenia. Furthermore, there was a significant positive correlation between the CSB-J composite score and the BACS-J composite score. A factor analysis showed a three-factor model consisting of memory, speed, and social cognition factors. CONCLUSIONS/SIGNIFICANCE: This study suggests that the CSB-J is a useful and rapid automatically administered computerized battery for assessing broad cognitive domains in Japanese patients with schizophrenia
Dual-Reporter Phenotypic Assay for Human Immunodeficiency Viruses▿
We have established a novel human immunodeficiency virus (HIV) tandem-reporter assay using HIV receptor-transduced NP-2 cells with long terminal repeat-controlled β-galactosidase, inserted internal ribosome entry site, and secretary alkaline phosphatase genes. This assay allows users to detect replication of clinical isolates, indicating its useful application as an HIV phenotypic assay
Release of the Repressive Activity of Rice DELLA Protein SLR1 by Gibberellin Does Not Require SLR1 Degradation in the gid2 Mutant[W]
The rice (Oryza sativa) DELLA protein SLR1 acts as a repressor of gibberellin (GA) signaling. GA perception by GID1 causes SLR1 protein degradation involving the F-box protein GID2; this triggers GA-associated responses such as shoot elongation and seed germination. In GA-insensitive and GA biosynthesis mutants, SLENDER RICE1 (SLR1) accumulates to high levels, and the severity of dwarfism is usually correlated with the level of SLR1 accumulation. An exception is the GA-insensitive F-box mutant gid2, which shows milder dwarfism than mutants such as gid1 and cps even though it accumulates higher levels of SLR1. The level of SLR1 protein in gid2 was decreased by loss of GID1 function or treatment with a GA biosynthesis inhibitor, and dwarfism was enhanced. Conversely, overproduction of GID1 or treatment with GA3 increased the SLR1 level in gid2 and reduced dwarfism. These results indicate that derepression of SLR1 repressive activity can be accomplished by GA and GID1 alone and does not require F-box (GID2) function. Evidence for GA signaling without GID2 was also provided by the expression behavior of GA-regulated genes such as GA-20oxidase1, GID1, and SLR1 in the gid2 mutant. Based on these observations, we propose a model for the release of GA suppression that does not require DELLA protein degradation
Affinity selection and sequence-activity relationships of HIV-1 membrane fusion inhibitors directed at the drug-resistant variants
Enfuvirtide is the first approved membrane fusion inhibitor against HIV-1. Although this drug is effective against multi-drug resistant strains, the emergence of enfuvirtide-resistant strains has been reported in patients who have received an enfuvirtide-containing regimen. Based on the high affinity of synthetic HIV-1 gp41 C-terminal heptad repeat (C-HR) peptides to the counterpart trimeric N-terminal heptad repeat (N-HR) coiled-coil structure, a novel screening approach has been established to facilitate the identification of potent fusion inhibitors against wild-type and enfuvirtide-resistant HIV-1. In this process, affinity selection using histidine-tagged N-HR peptides with the sequences derived from wild-type and resistant strains efficiently captured potent inhibitory peptides from a pool of highly water-soluble C-HR peptides with α-helix-inducible motifs. A highly potent peptide was found from a single amino acid substitution observed in an enfuvirtide-resistant variant as well as peptides with unprecedented modifications at the mutated site
Electrostatically constrained α-helical peptide inhibits replication of HIV-1 resistant to enfuvirtide.
Alpha-helical peptides, such as T-20 (enfuvirtide) and C34, derived from the gp41 carboxyl-terminal heptad repeat (C-HR) of HIV-1, inhibit membrane fusion of HIV-1 and the target cells. Although T-20 effectively suppresses the replication of multi-drug resistant HIV variants both in vitro and in vivo, prolonged therapy with T-20 induces emergence of T-20 resistant variants. In order to suppress the emergence of such resistant variants, we introduced charged and hydrophilic amino acids, glutamic acid (E) and lysine (K), at the solvent accessible site of C34. In particular, the modified peptide, SC34EK, demonstrates remarkably potent inhibition of membrane fusion by the resistant HIV-1 variants as well as wild-type viruses. The activity was specific to HIV-1 and little influenced by serum components. We found a strong correlation between the anti-HIV-1 activities of these peptides and the thermostabilities of the 6-helix bundles that are formed with these peptides. We also obtained the crystal structure of SC34EK in complex with a 36 amino acid sequence (N36) comprising the amino-terminal heptad repeat of HIV-1. The EK substitutions in the sequence of SC34EK were directed toward the solvent and generated an electrostatic potential, which may result in enhanced alpha-helicity of the peptide inhibitor. The 6-helix bundle complex of SC34EK with N36 appears to be structurally similar to that of C34 and N36. Our approach to enhancing alpha-helicity of the peptide inhibitor may enable future design of highly effective and specific HIV-1 inhibitors
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