Elderly patient with 5q spinal muscular atrophy type 4 markedly improved by Nusinersen

Available online 17 May 2020.ArticleJournal of the Neurological Sciences.415:116901(2020)journal articl

Validity of reduced radiation dose for localized diffuse large B-cell lymphoma showing a good response to chemotherapy

To evaluate the validity of a decrease in the radiation dose for patients who were good responders to chemotherapy for localized diffuse large B-cell lymphoma (DLBCL), 91 patients with localized DLBCL who underwent radiotherapy after multi-agent chemotherapy from 1988-2008 were reviewed. Exclusion criteria were as follows: central nervous system or nasal cavity primary site, or Stage II with bulky tumor (>= 10 cm). Of these patients, 62 were identified as good responders to chemotherapy. They were divided into two groups receiving either a higher or a lower radiation dose (32-50.4 Gy or 15-30.6 Gy, respectively). There were no statistically significant differences between the lower and higher dose groups in progression-free survival, locoregional progression-free survival or overall survival. Adaptation of decreased radiation dose may be valid for localized DLBCL patients who show a good response to chemotherapy.ArticleJOURNAL OF RADIATION RESEARCH. 55(2):359-363 (2014)journal articl

Distinct temporal integration of noradrenaline signaling by astrocytic second messengers during vigilance

Astrocytes may function as mediators of the impact of noradrenaline on neuronal function. Activation of glial α1-adrenergic receptors triggers rapid astrocytic Ca2+ elevation and facilitates synaptic plasticity, while activation of β-adrenergic receptors elevates cAMP levels and modulates memory consolidation. However, the dynamics of these processes in behaving mice remain unexplored, as do the interactions between the distinct second messenger pathways. Here we simultaneously monitored astrocytic Ca2+ and cAMP and demonstrate that astrocytic second messengers are regulated in a temporally distinct manner. In behaving mice, we found that while an abrupt facial air puff triggered transient increases in noradrenaline release and large cytosolic astrocytic Ca2+ elevations, cAMP changes were not detectable. By contrast, repeated aversive stimuli that lead to prolonged periods of vigilance were accompanied by robust noradrenergic axonal activity and gradual sustained cAMP increases. Our findings suggest distinct astrocytic signaling pathways can integrate noradrenergic activity during vigilance states to mediate distinct functions supporting memory

Enhanced Recombinant Protein Productivity by Genome Reduction in Bacillus subtilis

The emerging field of synthetic genomics is expected to facilitate the generation of microorganisms with the potential to achieve a sustainable society. One approach towards this goal is the reduction of microbial genomes by rationally designed deletions to create simplified cells with predictable behavior that act as a platform to build in various genetic systems for specific purposes. We report a novel Bacillus subtilis strain, MBG874, depleted of 874 kb (20%) of the genomic sequence. When compared with wild-type cells, the regulatory network of gene expression of the mutant strain is reorganized after entry into the transition state due to the synergistic effect of multiple deletions, and productivity of extracellular cellulase and protease from transformed plasmids harboring the corresponding genes is remarkably enhanced. To our knowledge, this is the first report demonstrating that genome reduction actually contributes to the creation of bacterial cells with a practical application in industry. Further systematic analysis of changes in the transcriptional regulatory network of MGB874 cells in relation to protein productivity should facilitate the generation of improved B. subtilis cells as hosts of industrial protein production

Nonsense mutation in CFAP43 causes normal-pressure hydrocephalus with ciliary abnormalities

OBJECTIVE: To identify genes related to normal-pressure hydrocephalus (NPH) in one Japanese family with several members with NPH. METHODS:We performed whole-exome sequencing (WES) on a Japanese family with multiple individuals with NPH and identified a candidate gene.Then we generated knockout mouse using CRISPR/Cas9 to confirm the effect of the candidate gene on the pathogenesis of hydrocephalus.RESULTS: In WES, we identified a loss-of-function variant in CFAP43 that segregated with the disease. CFAP43 encoding cilia- and flagella-associated protein is preferentially expressed in the testis.Recent studies have revealed that mutations in this gene cause male infertility owing to morphologic abnormalities of sperm flagella. We knocked out mouse ortholog Cfap43 using CRISPR/Cas9 technology, resulting in Cfap43-deficient mice that exhibited a hydrocephalus phenotype with morphologic abnormality of motile cilia. CONCLUSION: Our results strongly suggest that CFAP43 is responsible for morphologic or movement abnormalities of cilia in the brain that result in NPH

A Comprehensive Resource of Interacting Protein Regions for Refining Human Transcription Factor Networks

Large-scale data sets of protein-protein interactions (PPIs) are a valuable resource for mapping and analysis of the topological and dynamic features of interactome networks. The currently available large-scale PPI data sets only contain information on interaction partners. The data presented in this study also include the sequences involved in the interactions (i.e., the interacting regions, IRs) suggested to correspond to functional and structural domains. Here we present the first large-scale IR data set obtained using mRNA display for 50 human transcription factors (TFs), including 12 transcription-related proteins. The core data set (966 IRs; 943 PPIs) displays a verification rate of 70%. Analysis of the IR data set revealed the existence of IRs that interact with multiple partners. Furthermore, these IRs were preferentially associated with intrinsic disorder. This finding supports the hypothesis that intrinsically disordered regions play a major role in the dynamics and diversity of TF networks through their ability to structurally adapt to and bind with multiple partners. Accordingly, this domain-based interaction resource represents an important step in refining protein interactions and networks at the domain level and in associating network analysis with biological structure and function

Photoelectrochemical properties of dye-dispersing allophane–titania composite electrodes

Dye-dispersing allophane-titania composite electrodes were prepared from titanium alkoxide sols containing dye and allophane. The photoelectric conversion properties of the electrodes were investigated by photoelectrochemical measurements. The photocurrent values in the UV range decreased with an increase in the allophane content, whereas those in the visible range were increased by adding 1.0% (Al/Ti ratio) allophane. As a small amount of allophane nanoparticles were highly dispersed in the titania electrodes, the dye molecules were dispersed in the electrodes without decreasing the efficiency of the electron injection from the dye to the titania conduction band. The dye molecules dispersed on the titania nanoparticle surface were capped with allophane nanoparticles which prevented desorption. The dye molecules strongly interacted with the titania nanoparticle surface and efficiently injected the excited electrons into the titania conduction band. (C) 2015 Elsevier B.V. All rights reserved.ArticleAPPLIED CLAY SCIENCE. 107:138-144 (2015)journal articl

A literature review on neonate's brain activity for sensory experience <Review>

目的: 脳科学的手法の1つである近赤外分光法(near infrared spectroscopy : NIRS)を測定用具とした感覚刺激に対する新生児の大脳皮質の神経活動に関する研究を概観し, 大脳皮質の神経活動と看護ケアの関連を検討することの意義と課題を明らかにすること. 方法: 医中誌Web, PubMed(収載: 1993～2008年)をデータベースとし, 検索式(新生児OR早産児)AND(近赤外分光法), (neonates OR infants)AND(near infrared spectroscopy)を用いて収集した文献のうちNIRS指標を大脳皮質の神経活動指標として用いていた15文献について検討した. 結果: 検討された感覚刺激は「聴覚刺激」「視覚刺激」「侵害受容性刺激(採血)」「嗅覚刺激」「受動運動」で, 刺激に対する神経活動の測定部位は関連する感覚野か前頭葉であった. 対象は正常新生児又はNICU入院児で, 早産児を対象とした研究は侵害受容性刺激(採血)に関する研究が多かった. 刺激に対する神経活動時の測定部位での反応として, 酸化型ヘモグロビンや総ヘモグロビンの上昇が見られていたが, 研究間で刺激や測定部位が一定でなく, 刺激に対するNIRS指標の変化は十分に明らかではなかった. 結論: NIRSは既存の測定用具では評価できなかった新生児の感覚的経験を客観的に評価できることから, 新しい測定方法として期待されている一方, 測定用具としての感度を検討している段階であり, 既存の生理・行動指標と合わせた観察研究などの基礎的な研究の積み重ねが必要であると考えられた.Aim: The aim of this study was to survey neonate's brain activity for sensory experience and to clarify the meaning and issue of using cerebral monitoring technique for developmental care research. Method: A literature review covering the period from 1993 to 2008 was carried out using electronic database (Ichushi Web, PubMed), using the flowing formula; (neonates OR infants) AND (near infrared spectroscopy: NIRS). Fifteen researches were selected and organized. Result: The articles ware classified into five categories: the response to auditory stimulation, the response to visual stimulation, the response to pain stimulation, the response to olfactory stimulation, and the response to passive movement. Measurement regions were sensory parts of stimulation or frontal lobe. Subjects were normal or sick neonates, particularly preterm infants were surveyed about pain response. In many articles, oxy-hemoglobin and total-hemoglobin increased at brain activity for sensory stimulation, however it was unclear the well-defined pattern of regional brain activation as there were many kinds of stimulation and different measurement regions among articles. Conclusion: NIRS was thought as a new objective method of measuring sensory experience among neonates. However, the sensitivity of NIRS was not established. It was thought that fundamental research such as observational researches were required to establish well-defined brain responses of using NIRS

Suppl Data1.xlsx Supplementary materials to Ozawa et al. (2023) [DOI: 10.3390/ijms241713590]

Suppl Data1.xlsx Supplementary materials to Ozawa et al. (2023) [DOI: 10.3390/ijms241713590]</p