Docosahexaenoic acid contributes to increased CaMKII protein expression and a tendency to increase nNOS protein expression in differentiated NG108-15 cells.

Docosahexaenoic acid (DHA; 22:6n-3), an n-3 polyunsaturated fatty acid, has various important roles in brain functions. Nitric oxide (NO) produced by neuronal NO synthase (nNOS) and Ca/calmodulindependent protein kinase II (CaMKII) is also involved in brain functions. We investigated the influence of DHA on nNOS and CaMKII protein expression in differentiated NG108-15 cells.

Docosahexaenoic Acid Increases Vesicular Glutamate Transporter 2 Protein Levels in Differentiated NG108-15 Cells.

Docosahexaenoic acid (DHA; 22:6n-3), which is enriched in the neuronal membrane, plays a variety of roles in the brain. Vesicular glutamate transporters (VGLUTs) are responsible for incorporating glutamine into synaptic vesicles. We investigated the influence of DHA on the fatty acid profile and the levels of VGLUT1 and VGLUT2 proteins in differentiated NG108-15 cells, a neuroblastoma-glioma hybrid cell line.

Development and Preclinical Study of Free Radical Imaging Using Field-Cycling Dynamic Nuclear Polarization MRI.

Free radicals, such as metabolic intermediates, reactive oxygen species, and metal enzymes, are key substances in organisms, although they can also cause various oxidative diseases. Thus, free radical imaging should be considered as the ultimate form of metabolic imaging. Unfortunately, electron spin resonance (ESR) imaging has inherent disadvantages, such as free radicals with large linewidths generating blurred images and the presence of two or more free radicals resulting in a complicated imaging procedure.

Clinical and Genetic Features of Patients With TNFRSF1A Variants in Japan: Findings of a Nationwide Survey.

Objective: To elucidate the clinical and genetic features of patients with TNFRSF1A variants in Japan using data obtained from a nationwide survey conducted by the Ministry of Health, Labor, and Welfare of Japan study group for tumor necrosis factor receptor-associated periodic syndrome (TRAPS).

Methods: Inquiries were sent to 2,900 departments of internal medicine and pediatrics in all hospitals with more than 200 beds in Japan, asking whether they had patients in whom TRAPS was suspected. Genetic tests for TNFRSF1A, MEFV, and MVK were performed on 169 patients.

A definitive haplotype map of structural variations determined by microarray analysis of duplicated haploid genomes.

Complete hydatidiform moles (CHMs) are tissues carrying duplicated haploid genomes derived from single sperms, and detecting copy number variations (CNVs) in CHMs is assumed to be sensitive and straightforward methods. We genotyped 108 CHM genomes using Affymetrix SNP 6.0 (GEO#: GSE18642) and Illumina 1 M-duo (GEO#: GSE54948).

SNP55, a new functional polymorphism of MDM2-P2 promoter, contributes to allele-specific expression of MDM2 in endometrial cancers.

Background: The functional single nucleotide polymorphism (SNP) in the MDM2 promoter region, SNP309, is known to be associated with various diseases, particularly cancer. Although many studies have been performed to demonstrate the mechanism of allele-specific expression (ASE) on SNP309, they have only utilized in vitro techniques. It is unknown whether ASE of MDM2 is ascribed solely to SNP309, in vivo.

Genetic analysis of a case of glioblastoma with oligodendroglial component arising during the progression of diffuse astrocytoma.

The most recent definition of glioblastoma with oligodendroglioma component (GBMO) assigned clinical significance to the observation of oligodendroglial foci within glioblastomas. However, the pathological mechanism of its histogenesis has not yet been determined. We report the genetic analysis of a GBMO case that evolved from an astrocyte lineage.

GENESUS: a two-step sequence design program for DNA nanostructure self-assembly.

DNA has been recognized as an ideal material for bottom-up construction of nanometer scale structures by self-assembly. The generation of sequences optimized for unique self-assembly (GENESUS) program reported here is a straightforward method for generating sets of strand sequences optimized for self-assembly of arbitrarily designed DNA nanostructures by a generate-candidates-and-choose-the-best strategy. A scalable procedure to prepare single-stranded DNA having arbitrary sequences is also presented.

Familial acorea, microphthalmia and cataract syndrome.

Purpose: To describe the clinical features of members of a family with acorea, microphthalmia and cataract syndrome. In addition, to perform linkage analysis on family members to determine possible candidate genes.

Methods: Comprehensive ophthalmic examinations were performed on five affected members of a family consisting of a paternal grandmother, father and three children.

ZNF408 is mutated in familial exudative vitreoretinopathy and is crucial for the development of zebrafish retinal vasculature.

Familial exudative vitreoretinopathy (FEVR) is a genetically heterogeneous disorder characterized by abnormal vascularization of the peripheral retina, which can result in retinal detachment and severe visual impairment. In a large Dutch FEVR family, we performed linkage analysis, exome sequencing, and segregation analysis of DNA variants. We identified putative disease-causing DNA variants in proline-alanine-rich ste20-related kinase (c.

Genetic variants of FZD4 and LRP5 genes in patients with advanced retinopathy of prematurity.

Purpose: Retinopathy of prematurity (ROP) is a complex disease with a genetic predisposition, but little is known about its genetic background. It has a clinical resemblance to familial exudative vitreoretinopathy (FEVR), a hereditary disease characterized by defects in the development of retinal vessels. Several studies have suggested that mutations in the causative genes for FEVR may account for a proportion of advanced ROP, but conflicting data have also been reported for some variants.

Loss of activating EGFR mutant gene contributes to acquired resistance to EGFR tyrosine kinase inhibitors in lung cancer cells.

Non-small-cell lung cancer harboring epidermal growth factor receptor (EGFR) mutations attains a meaningful response to EGFR-tyrosine kinase inhibitors (TKIs). However, acquired resistance to EGFR-TKIs could affect long-term outcome in almost all patients. To identify the potential mechanisms of resistance, we established cell lines resistant to EGFR-TKIs from the human lung cancer cell lines PC9 and11-18, which harbored activating EGFR mutations.

Genome-wide repression of NF-κB target genes by transcription factor MIBP1 and its modulation by O-linked β-N-acetylglucosamine (O-GlcNAc) transferase.

The transcription factor c-MYC intron binding protein 1 (MIBP1) binds to various genomic regulatory regions, including intron 1 of c-MYC. This factor is highly expressed in postmitotic neurons in the fetal brain and may be involved in various biological steps, such as neurological and immunological processes. In this study, we globally characterized the transcriptional targets of MIBP1 and proteins that interact with MIBP1.

A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese.

Systemic lupus erythematosus (SLE) is an autoimmune disease that causes multiple organ damage. Although recent genome-wide association studies (GWAS) have contributed to discovery of SLE susceptibility genes, few studies has been performed in Asian populations. Here, we report a GWAS for SLE examining 891 SLE cases and 3,384 controls and multi-stage replication studies examining 1,387 SLE cases and 28,564 controls in Japanese subjects.

Hereditary angioedema in Japan: genetic analysis of 13 unrelated cases.

Introduction: The molecular bases and clinical features of hereditary angioedema (HAE) have not been systematically documented in Japan or in other Asian countries. Thus, the authors researched the genetic and clinical characteristics of Japanese patients with HAE.

Methods: The authors analyzed the CIINH gene for mutations in 13 unrelated Japanese patients with HAE by means of the polymerase chain reaction and nucleotide sequencing.

Mutations in the TSPAN12 gene in Japanese patients with familial exudative vitreoretinopathy.

Purpose: To search for mutations in the TSPAN12 gene in 90 Japanese probands with familial exudative vitreoretinopathy (FEVR) and their family members and to determine the types and frequencies of the mutations.

Design: Laboratory investigation and clinical case analyses.

Methods: Direct sequencing after polymerase chain reaction of the coding exons of TSPAN12 was performed for 90 probands with FEVR and some of their family members.

A definitive haplotype map as determined by genotyping duplicated haploid genomes finds a predominant haplotype preference at copy-number variation events.

The majority of complete hydatidiform moles (CHMs) harbor duplicated haploid genomes that originate from sperm. This makes CHMs more advantageous than conventional diploid cells for determining haplotypes of SNPs and copy-number variations (CNVs), because all of the genetic variants in a CHM genome are homozygous. Here we report SNP and CNV haplotype structures determined by analysis of 100 CHMs from Japanese subjects via high-density DNA arrays.

Association of killer cell immunoglobulin-like receptor 2DL5 with systemic lupus erythematosus and accompanying infections.

Objective: Identification of the association of killer cell immunoglobulin-like receptor (KIR) genes with SLE and accompanying infections.

Methods: Presence or absence of all 14 KIR genes was studied for association with SLE by case-control studies. A total of 417 SLE cases, 72 RA cases and 256 controls, all of Japanese descent, were enrolled.

Impact of group IVA cytosolic phospholipase A2 gene polymorphisms on phenotypic features of patients with familial adenomatous polyposis.

Objective: Group IVA cytosolic phospholipase A(2) (cPLA(2)alpha) plays a key role in tumorigenesis via generating arachidonic acids as the substrate of cyclooxygenase. The aim of this study was to elucidate the possible associations between cPLA ( 2 )alpha gene polymorphisms and phenotypic features of patients with familial adenomatous polyposis (FAP).

Patients And Methods: A tag single nucleotide polymorphisms (SNPs)-based genotype-phenotype association study of the cPLA ( 2 )alpha gene was conducted in 73 Japanese patients from 59 families with FAP.

Estimation of SNP allele frequencies by SSCP analysis of pooled DNA.

The single strand conformation polymorphism (SSCP) method is a sensitive technique used to detect subtle sequence differences in PCR-amplified DNA fragments as separated peaks in electrophoretic analysis. In this chapter, we focus on SSCP analysis for quantifying polymorphic alleles rather than scanning for mutations. Short fragments carrying single nucleotide polymorphisms are amplified from individual and pooled DNA samples, then the products are labeled with fluorescent dyes and analyzed by automated capillary electrophoresis under nondenaturing conditions.

Evaluation of haplotype inference using definitive haplotype data obtained from complete hydatidiform moles, and its significance for the analyses of positively selected regions.

The haplotype map constructed by the HapMap Project is a valuable resource in the genetic studies of disease genes, population structure, and evolution. In the Project, Caucasian and African haplotypes are fairly accurately inferred, based mainly on the rules of Mendelian inheritance using the genotypes of trios. However, the Asian haplotypes are inferred from the genotypes of unrelated individuals based on population genetics, and are less accurate.