担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Neuroscience Research  

Fused in sarcoma (FUS) is an RNA binding protein that is involved in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). To establish the common marmoset (Callithrix jacchus) as a model for FTLD, we generated a stereotaxic injection-based marmoset model of FUS-silencing. We designed shRNAs against the marmoset FUS gene and generated an AAV9 virus encoding the most effective shRNA against FUS (shFUS). The AAV encoding shFUS (AAV-shFUS) was introduced into the frontal cortex of young adult marmosets, whereas AAV encoding a control shRNA was injected into the contralateral side. We obtained approximately 70–80% silencing of FUS following AAV-shFUS injection. Interestingly, FUS-silencing provoked a proliferation of astrocytes and microglias. Since FTLD is characterized by various emotional deficits, it would be helpful to establish a marmoset model of FUS-silencing in various brain tissues for investigating the pathomechanism of higher cognitive and behavioral dysfunction.

DOI： 10.1016/j.neures.2017.08.006

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DOI： 10.1016/j.jns.2017.08.920

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記述言語：英語   出版者・発行元：Cell Reports  

Fused in sarcoma (FUS) and splicing factor, proline- and glutamine-rich (SFPQ) are RNA binding proteins that regulate RNA metabolism. We found that alternative splicing of the Mapt gene at exon 10, which generates 4-repeat tau (4R-T) and 3-repeat tau (3R-T), is regulated by interactions between FUS and SFPQ in the nuclei of neurons. Hippocampus-specific FUS- or SFPQ-knockdown mice exhibit frontotemporal lobar degeneration (FTLD)-like behaviors, reduced adult neurogenesis, accumulation of phosphorylated tau, and hippocampal atrophy with neuronal loss through an increased 4R-T/3R-T ratio. Normalization of this increased ratio by 4R-T-specific silencing results in recovery of the normal phenotype. These findings suggest a biological link among FUS/SFPQ, tau isoform alteration, and phenotypic expression, which may function in the early pathomechanism of FTLD.

DOI： 10.1016/j.celrep.2017.01.013

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記述言語：英語   出版者・発行元：Nagoya Journal of Medical Science  

Voxel-based analysis (VBA) of diffusion tensor images (DTI) and voxel-based morphometry (VBM) in patients with multiple sclerosis (MS) can sensitively detect occult tissue damage that underlies pathological changes in the brain. In the present study, both at the start of fingolimod and post-four months clinical remission, we assessed four patients with MS who were evaluated with VBA of DTI, VBM, and fluid-attenuated inversion recovery (FLAIR). DTI images for all four patients showed widespread areas of increased mean diffusivity (MD) and decreased fractional anisotropy (FA) that were beyond the highintensity signal areas across images. After four months of continuous fingolimod therapy, DTI abnormalities progressed; in particular, MD was significantly increased, while brain volume and high-intensity signals were unchanged. These findings suggest that VBA of DTI (e.g., MD) may help assess MS demyelination as neuroinflammatory conditions, even though clinical manifestations of MS appear to be in complete remission during fingolimod.

DOI： 10.18999/nagjms.78.4.455

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出版者・発行元：BMC Medical Education  

Background: The study of communication skills of Asian medical students during structured Problem-based Learning (PBL) seminars represented a unique opportunity to assess their critical thinking development. This study reports the first application of the health education technology, content analysis (CA), to a Japanese web-based seminar (webinar). Methods. The authors assigned twelve randomly selected medical students from two universities and two clinical instructors to two virtual classrooms for four PBL structured tutoring sessions that were audio-video captured for CA. Both of the instructors were US-trained physicians. This analysis consisted of coding the students' verbal comments into seven types, ranging from trivial to advanced knowledge integration comments that served as a proxy for clinical thinking. Results: The most basic level of verbal simple responses accounted for a majority (85%) of the total students' verbal comments. Only 15% of the students' comments represented more advanced types of critical thinking. The male students responded more than the female students; male students attending University 2 responded more than male students from University 1. The total mean students' verbal response time for the four sessions with the male instructor was 6.9%; total mean students' verbal response time for the four sessions with the female instructor was 19% (p < 0.05). Conclusions: This report is the first to describe the application of CA to a multi-university real time audio and video PBL medical student clinical training webinar in two Japanese medical schools. These results are preliminary, mostly limited by a small sample size (n = 12) and limited time frame (four sessions). CA technology has the potential to improve clinical thinking for medical students. This report may stimulate improvements for implementation. © 2013 Takata et al.; licensee BioMed Central Ltd.

DOI： 10.1186/1472-6920-13-156

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記述言語：英語   出版者・発行元：Urology  

Objective: To determine the effect of tamsulosin hydrochloride on blood flow in the submucosal capillaries of the bladder (SCB) in a rat model of bladder outlet obstruction (BOO) using a pencil lens charge-coupled device microscopy system. Materials and Methods: BOO was established in rats by partial ligature of the proximal urethra and was maintained for 2 weeks. Tamsulosin or saline (control) was subcutaneously administered using an osmotic pump for 2 weeks immediately after surgery. The pencil lens charge-coupled device microscopy system was used to visualize the bladder microcirculation and quantitatively assess the blood flow in the SCB by measuring the velocity of the blood flow at the base and dome of the bladder. The blood flow in the SCB of the sham-operated rats, control BOO rats, and tamsulosin-treated BOO rats was compared. Results: The blood flow in the SCB was significantly greater at the base than at the dome of the bladder. The reduction in blood flow through the SCB at the base and dome of the bladder was more significant in the BOO rats than in the sham-operated rats. However, after pretreatment with tamsulosin, the BOO rats showed a significant increase in blood flow through the SCB at the base and dome of the bladder compared with that of the control rats. The pencil lens charge-coupled device microscopy system image showed that the BOO rats had chronic ischemic capillary injury, which was ameliorated by tamsulosin. Conclusion: The results of the present study suggest that tamsulosin hydrochloride protects the SCB from ischemic injury after BOO. © 2013 Elsevier Inc. All Rights Reserved.

DOI： 10.1016/j.urology.2012.09.008

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