統合失調症初発エピソードの認知機能障害の経過と発症5 年経過群との比較

OBJECTIVE: The course of neurocognitive deficits in schizophrenia has not yet been established. Therefore, we followed patients with first-episode schizophrenia to verify the course of these deficits. METHODS:In Study 1, tests of neurocognitive functioning were administered to patients with first-episode schizophrenia (FE group) every 6 months. Of the 26 patients who completed the baseline assessment, 19 completed a 6-month follow-up, and 13 completed a 1-year follow-up. In Study 2, 19 patients in FE group at 6-months when the neuropsychological measures was less influenced by psychotic symptoms and other patients who experienced schizophrenia 5-years earlier (5-year group) were compared. RESULTS:In Study 1, verbal memory, motor speed, and executive functions significantly improved at the 1-year follow-up. In Study 2, patients in 5-year group performed worse in verbal memory and executive functions than patients in FE at 6-month group, but marginally but significantly better in verbal fluency. CONCLUSIONS:Verbal memory, executive functions, and verbal fluency were significantly different between 5-year group and FE at 6-month group, and may indicate progression of schizophrenia. Executive functions may reflect the state of psychosis. Working memory and processing speed which did not change significantly from onset are needed to verify the course in further research.博士（医学）・甲610号・平成26年3月17

IRE1-XBP1 Pathway of the Unfolded Protein Response Is Required during Early Differentiation of C2C12 Myoblasts

ArticleInternational Journal of Molecular Sciences. 21(1): 182. (2019)journal articl

Triethylated chromones with substituted naphthalenes as tubulin inhibitors

Previously synthesized 2-(benzo[]thiophene-3′-yl)-6,8,8-triethyldesmosdumotin B (, TEDB-TB) and 2-(naphth-1′-yl)-6,8,8-triethyldesmosdumotin B () showed potent activity against multiple human tumor cell lines, including a multidrug-resistant (MDR) subline, by targeting spindle formation and/or the microtubule network. Consequently, ester analogues of hydroxylated naphthyl substituted TEBDs (–) were prepared and evaluated for their effects on tumor cell proliferation and on tubulin assembly. Among all new compounds, compound , a 4′-acetoxynaphthalen-1′-yl derivative, displayed the most potent antiproliferative activity (IC 0.2–5.7 μM). Selected analogues were confirmed to be tubulin assembly inhibitors in cell-free and cell-based assays using MDR tumor cells. The new analogues partially inhibited colchicine binding to tubulin, suggesting their binding mode would be different from that of colchicine. This observation was supported by computational docking model analyses. Thus, the newly synthesized triethylated chromones with esterified naphthalene groups have good potential for development as a new class of mitotic inhibitors that target tubulin

Genomes of Neutrophilic Sulfur-Oxidizing Chemolithoautotrophs Representing 9 Proteobacterial Species From 8 Genera

Even in the current era of metagenomics, the interpretation of nucleotide sequence data is primarily dependent on knowledge obtained from a limited number of microbes isolated in pure culture. Thus, it is of fundamental importance to expand the variety of strains available in pure culture, to make reliable connections between physiological characteristics and genomic information. In this study, two sulfur oxidizers that potentially represent two novel species were isolated and characterized. They were subjected to whole-genome sequencing together with 7 neutrophilic and chemolithoautotrophic sulfur-oxidizing bacteria. The genes for sulfur oxidation in the obtained genomes were identified and compared with those of isolated sulfur oxidizers in the classes Betaproteobacteria and Gammaproteobacteria. Although the combinations of these genes in the respective genomes are diverse, typical combinations corresponding to three types of core sulfur oxidation pathways were identified. Each pathway involves one of three specific sets of proteins, SoxCD, DsrABEFHCMKJOP, and HdrCBAHypHdrCB. All three core pathways contain the SoxXYZAB proteins, and a cytoplasmic sulfite oxidase encoded by soeABC is a conserved component in the core pathways lacking SoxCD. Phylogenetically close organisms share same core sulfur oxidation pathway, but a notable exception was observed in the family ‘Sulfuricellaceae’. In this family, some strains have either core pathway involving DsrABEFHCMKJOP or HdrCBAHypHdrCB, while others have both pathways. A proteomics analysis showed that proteins constituting the core pathways were produced at high levels. While hypothesized function of HdrCBAHypHdrCB is similar to that of Dsr system, both sets of proteins were detected with high relative abundances in the proteome of a strain possessing genes for these proteins. In addition to the genes for sulfur oxidation, those for arsenic metabolism were searched for in the sequenced genomes. As a result, two strains belonging to the families Thiobacillaceae and Sterolibacteriaceae were observed to harbor genes encoding ArxAB, a type of arsenite oxidase that has been identified in a limited number of bacteria. These findings were made with the newly obtained genomes, including those from 6 genera from which no genome sequence of an isolated organism was previously available. These genomes will serve as valuable references to interpret nucleotide sequences

Role of C-Terminal Region of HA-33 Component of Botulinum Toxin in Hemagglutination

Clostridium botulinum D型1873株とC型Yoichi株の産生するプロジェニター毒素から得られた1種類のサブコンポーネントである血球凝集素（HA-33）は、C及びD型参照株のそれより少し小さい分子サイズであるが、他のコンポーネントのの大きさに違いがないことが、SDS-PAGEを用いて見いだされた。すなわち、HA-33のN-及びC-末端シーケンス分析に基つき、両株のHA-33淡白において特異的なサイトでC-末端から33アミノ酸残基の欠落があることが見いだされた。両株のプロジェニター毒素は、参照株毒素の血球凝集力価2かそれ以下の弱い血球凝集活性を示すが、赤血球に吸着することはできない。これらの結果はHA-33の短いC-末端部分が、ボツリヌスプロジェンター毒素の血球凝集活性において重要な役割を果たしていることを示す。さらに、シーケンスモチーフの探索により、HA-33のC-末端部分は炭化水素認識サブドメインを持っていることが推測された

Development of a soft X-ray angle-resolved photoemission system applicable to 100 µm crystals

A soft X-ray angle-resolved photoemission system applicable to 100 µm crystals has been developed