The p250GAP Gene Is Associated with Risk for Schizophrenia and Schizotypal Personality Traits

BACKGROUND: Hypofunction of the glutamate N-Methyl-d-aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. p250GAP is a brain-enriched NMDA receptor-interacting RhoGAP. p250GAP is involved in spine morphology, and spine morphology has been shown to be altered in the post-mortem brains of patients with schizophrenia. Schizotypal personality disorder has a strong familial relationship with schizophrenia. Several susceptibility genes for schizophrenia have been related to schizotypal traits. METHODS: We first investigated the association of eight linkage disequilibrium-tagging single-nucleotide polymorphisms (SNPs) that cover the p250GAP gene with schizophrenia in a Japanese sample of 431 schizophrenia patients and 572 controls. We then investigated the impact of the risk genetic variant in the p250GAP gene on schizotypal personality traits in 180 healthy subjects using the Schizotypal Personality Questionnaire. RESULTS: We found a significant difference in genotype frequency between the patients and the controls in rs2298599 (χ(2) = 17.6, p = 0.00015). The minor A/A genotype frequency of rs2298599 was higher in the patients (18%) than in the controls (9%) (χ(2) = 15.5, p = 0.000083). Moreover, we found that subjects with the rs2298599 risk A/A genotype, compared with G allele carriers, had higher scores of schizotypal traits (F(1,178) = 4.08, p = 0.045), particularly the interpersonal factor (F(1,178) = 5.85, p = 0.017). DISCUSSION: These results suggest that a genetic variation in the p250GAP gene might increase susceptibility not only for schizophrenia but also for schizotypal personality traits. We concluded that the p250GAP gene might be a new candidate gene for susceptibility to schizophrenia

Cu,Zn-SOD deficiency induces the accumulation of hepatic collagen

<p>Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic diseases, and results in the development of fibrosis. Oxidative stress is thought to be one of the underlying causes of NAFLD. Copper/zinc superoxide dismutase (SOD1) is a primary antioxidative enzyme that scavenges superoxide anion radicals. Although SOD1 knockout (KO) mice have been reported to develop fatty livers, it is not known whether this lack of SOD1 leads to the development of fibrosis. Since the accumulation of collagen typically precedes liver fibrosis, we assessed the balance between the synthesis and degradation of collagen in liver tissue from SOD1 KO mice. We found a higher accumulation of collagen in the livers of SOD1 KO mice compared to wild type mice. The level of expression of HSP47, a chaperone of collagen, and a tissue inhibitor (TIMP1) of matrix metalloproteinases (a collagen degradating enzyme) was also increased in SOD1 KO mice livers. These results indicate that collagen synthesis is increased but that its degradation is inhibited in SOD1 KO mice livers. Moreover, SOD1 KO mice liver sections were extensively modified by advanced glycation end products (AGEs), which suggest that collagen in SOD1 KO mice liver might be also modified with AGEs and then would be more resistant to the action of collagen degrading enzymes. These findings clearly show that oxidative stress plays an important role in the progression of liver fibrosis.</p

Effects of Arabidopsis Ku80 deletion on the integration of the left border of T-DNA into plant chromosomal DNA via Agrobacterium tumefaciens

T-DNA integration into plant chromosomal DNA via Agrobacterium tumefaciens can be achieved by exploiting the double-strand break repair system of the host’s DNA. However, the detailed mechanism of T-DNA integration remains unclear. Here, a sequence analysis of the junction sequences of T-DNA and chromosomal DNA was performed to assess the mechanism of T-DNA integration. T-DNA was introduced into Arabidopsis wild-type and NHEJ-deficient ku80-mutant plants using the floral dip method; the junctions of the left border (LB) of T-DNA were subsequently analyzed by adapter PCR. The most frequent junction of the LB of T-DNA to chromosomal DNA (LB-to-ChrDNA) was of the filler DNA type in both lines. The lengths of direct or inverted repeat sequences within or around the filler DNA sequence were longer in the ku80 mutant. In addition, the frequency of T-DNA integration near the transcription start site was significantly higher in the ku80 mutant. Our observations suggest that the presence of the Ku80 protein affects the location of the integration of T-DNA and the pattern of the formation of repeat sequences within or around the filler DNA during LB integration into chromosomal DNA

Fabrication of Carboxylated Silicon Nitride Sensor Chips for Detection of Antigen–Antibody Reaction Using Microfluidic Reflectometric Interference Spectroscopy

In this study, we report label-free detection of alpha-fetoprotein (AFP), which has been used as a biomarker for hepatocellular carcinoma, by a microfluidic reflectometric interference spectroscopy (RIfS) system adopting a simple halogen light source and an inexpensive silicon-based sensor chip. Introduction of carboxy groups on a silicon nitride sensor chip to immobilize anti-AFP monoclonal antibody (anti-AFP) was carried out simply by immersion in aqueous solution containing triethoxysilylpropylmaleamic acid bearing a carboxy group and a silanol group. The RIfS system with the anti-AFP-immobilized sensor chip was found to give a reversible response through 100 on/off cycles using a regeneration buffer with high reproducibility (coefficient of variation (CV) = 5.7%). The limit of detection (LOD) of AFP was 100 ng mL^–1, and the measurement range spanned 3 orders of magnitude. Furthermore, the sensor chip showed no cross-reactivity with human serum albumin, Immunoglobulin G, transferrin, or fibrinogen at 100 μg mL^–1 without the use of blocking reagents such as bovine serum albumin. Consequently, the proposed RIfS system is a potentially effective tool for biomarker detection and in vitro diagnostics

Minimal Thioflavin T Modifications Improve Visual Discrimination of Guanine-Quadruplex Topologies and Alter Compound-Induced Topological Structures

We newly synthesized thioflavin T (ThT) analogs for which the methyl group at the <i>N</i>3 position on the benzothiazole ring was replaced with either a ((<i>p</i>-(dimethylamino)­benzoyl)­oxy)­ethyl group (ThT-DB) or a hydroxyethyl group (ThT-HE). In several neutral buffers, ThT-HE bound to a parallel guanine-quadruplex (G4) DNA and selectively emitted strong fluorescence at 74- to 240-fold higher intensities than those in the presence of double-stranded DNA (dsDNA), whereas ThT resulted in only 13- to 25-fold higher intensities. Furthermore, circular dichroism (CD) analyses using ThT, ThT-DB, and ThT-HE showed that these compounds could induce topological changes in G4. In addition, the different chemical structures of the <i>N</i>3 substituents could alter a G4–DNA conformation. These results indicate a great potential for <i>N</i>3-substituted ThT analogs as G4 probes and drug leads to achieve gene expression regulation

"Improvement of Agri-Food literacy for Children through farm Animal assisted education III"

本研究は, 幼稚園及び保育園の幼児を対象とした, 家畜介在教育(Farm Animal Assisted Education for Children:FAAEC)の発展を目指して行った。食農リテラシーとは, 人間生存の基本となる食と, それを可能とする農及び自然環境に関する認識, 評価, 実践を総合した能力のことであり, その能力を生命に対する認識とともに一体的に獲得するためには, 畑作や稲作の体験だけではなく家畜介在教育が必要であると考えられる。本研究では幼稚園における家畜介在教育のモデル動物としてウサギを取り上げている。本研究に先立って, 広島県内200の幼稚園を対象として行ったアンケート及び実地調査の結果, ウサギ飼育率は高いものの, ウサギの健康状態の悪い園も認められた。そこで, 家畜介在教育(FAAEC)を実施する前に, ウサギの飼育状態の改善が急務であると考えられた。本研究では, ウサギのQOLの向上を目指した, エンリッチメントの導入効果について検討した