An amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDFWe report a family with progressive myoclonic epilepsy who underwent whole-exome sequencing but was negative for pathogenic variants. Similar clinical courses of a devastating neurodegenerative phenotype of two affected siblings were highly suggestive of a genetic etiology, which indicates that the survey of genetic variation by whole-exome sequencing was not comprehensive. To investigate the presence of a variant that remained unrecognized by standard genetic testing, PacBio long-read sequencing was performed.
View Article and Find Full Text PDFSeveral expression systems for multiple guide RNA (gRNAs) have been developed in the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9) system to induce multiple-gene modifications in plants. Here, we evaluated mutation efficiencies in the tomato genome using multiplex CRISPR/Cas9 vectors consisting of various expression promoters with multiple gRNA expression combinations. In transgenic tomato calli induced with these vectors, mutation patterns varied depending on the promoters used to express .
View Article and Find Full Text PDFOncogenic and fusions were reported in solid tumors, including non-small cell lung cancer (NSCLC). DS-6051b is an oral, potent selective small molecule tyrosine kinase inhibitor. We report the safety, tolerability, efficacy, and pharmacokinetics of DS-6051b in 15 Japanese patients with NSCLC harboring fusions.
View Article and Find Full Text PDFThe success of human life in modern society is highly dependent on occupation. Therefore, it is very important for people to identify and develop a career plan that best suits their aptitude. Traditional test batteries for vocational aptitudes are not oriented to measure developmental changes in job suitability because repeated measurements can introduce bias as the content of the test batteries is learned.
View Article and Find Full Text PDFMany human characteristics must be evaluated to comprehensively understand an individual, and measurements of the corresponding cognition/behavior are required. Brain imaging by functional MRI (fMRI) has been widely used to examine brain function related to human cognition/behavior. However, few aspects of cognition/behavior of individuals or experimental groups can be examined through task-based fMRI.
View Article and Find Full Text PDFBackground: Effective social problem-solving abilities can contribute to decreased risk of poor mental health. In addition, physical activity has a favorable effect on mental health. These previous studies suggest that physical activity and social problem-solving ability can interact by helping to sustain mental health.
View Article and Find Full Text PDFBackground: Cytochrome P450 3A4 (CYP3A4) is an important drug-metabolizing enzyme that is expressed in the liver and small intestine of humans. Various factors influence the expression of CYP3A4, but gender difference in CYP3A4 expression remains debatable.
Objective: To clarify gender difference of hepatic and intestinal CYP3A4 in CYP3A-humanized mice generated by a human artificial chromosome (HAC) vector system.
Parthenocarpy in horticultural crop plants is an important trait with agricultural value for various industrial purposes as well as direct eating quality. Here, we demonstrate a breeding strategy to generate parthenocarpic tomato plants using the CRISPR/Cas9 system. We optimized the CRISPR/Cas9 system to introduce somatic mutations effectively into SlIAA9-a key gene controlling parthenocarpy-with mutation rates of up to 100% in the T0 generation.
View Article and Find Full Text PDFHomocysteine-induced endoplasmic reticulum (ER) protein (Herp) is an ER stress-inducible key regulatory component of ER-associated degradation (ERAD) that has been implicated in insulin hypersecretion in diabetic mouse models. Herp expression is tightly regulated. Additionally, Herp is a highly labile protein and interacts with various proteins, which are characteristic features of ubiquitinated protein.
View Article and Find Full Text PDFChitin is high in crystallinity in its natural form and does not dissolve into high temperature water (HTW), which often leads to decomposition reactions such as hydrolysis, deacetylation and dehydration when hydrothermally processed. In this work, we investigated the reactions of mechanically milled chitin in HTW. Mechanical milling pretreatment combined with HTW treatment improved the liquefaction of chitin giving a maximum water soluble fraction of 80%, where the untreated chitin was 55%.
View Article and Find Full Text PDF