Optically Detected Structural Change in the N-Terminal Region of the Voltage-Sensor Domain

AbstractThe voltage-sensor domain (VSD) is a functional module that undergoes structural transitions in response to membrane potential changes and regulates its effectors, thereby playing a crucial role in amplifying and decoding membrane electrical signals. Ion-conductive pore and phosphoinositide phosphatase are the downstream effectors of voltage-gated channels and the voltage-sensing phosphatase, respectively. It is known that upon transition, the VSD generally acts on the region C-terminal to S4. However, whether the VSD also induces any structural changes in the N-terminal region of S1 has not been addressed directly. Here, we report the existence of such an N-terminal effect. We used two distinct optical reporters—one based on the Förster resonance energy transfer between a pair of fluorescent proteins, and the other based on fluorophore-labeled HaloTag—and studied the behavior of these reporters placed at the N-terminal end of the monomeric VSD derived from voltage-sensing phosphatase. We found that both of these reporters were affected by the VSD transition, generating voltage-dependent fluorescence readouts. We also observed that whereas the voltage dependencies of the N- and C-terminal effects appear to be tightly coupled, the local structural rearrangements reflect the way in which the VSD is loaded, demonstrating the flexible nature of the VSD

建学の精神の徹底を図る初年次教育の実践と課題 ―ホスピタリティ概論の分析から―

本研究は、2017年度から始まった本学の初年次教育を定着させるとともに、新入生が大学での教育を理解し、建学の精神に代表される理念やディプロマポリシーを自分のものとして捉え、その実現に向けた主体的な学修の基盤を構築するという初年次教育の目標の達成を図ることにある。このためには、彼らの特性をとらえるとともに、彼らが初年次教育をどのように捉え、理解したかを把握しなければならない。そこで初年次教育の科目の一つとして開設された「ホスピタリティ概論」を活用して、全受講生を対象とした2つの調査を3年間実施した。1つ目の調査は入学当初の学生像をとらえ授業展開に生かすために学生の特徴を把握するものであり、第1回目の授業で実施された。2つ目の調査は授業内容の理解度を評価するものであり、第10回目に実施された。これらの回答を年度と学科毎に集計、分析した。その結果、次のことが明らかになった。①オープンキャンパスへの参加や進学希望状況などの本学入学に至る経緯が学科によって異なること、そして、入学当初には心身に不安を抱いている学生が、どの学科にも相当数存在すること。3年間の調査によって各学科の学生の特色が明らかになり、学科毎の適切な学修支援方策の作成に向けた示唆が得られたこと。②この講義を受けて、建学の精神であるホスピタリティの獲得に大学が力を入れており、その実現が求められていると多くの学生が認識していること、及び、本科目の重点目標である多様性の理解力の育成につながる他学科の学生とのコミュニケーションの機会に意義を見出していること等から、授業の目標達成に向けた順調な歩みが見られること。これらの結果及び他の科目の報告から、初年次教育が定着しつつあること、そして、その目標達成に向けた歩みが順調であると判断した。ただ、更なる充実のための課題も浮かび上がっている

Resting echocardiographic parameters to detect patients with less symptomatic primary mitral regurgitation who require exercise stress echocardiography

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Genetically encoded bioluminescent voltage indicator for multi-purpose use in wide range of bioimaging

We report development of the first genetically encoded bioluminescent indicator for membrane voltage called LOTUS-V. Since it is bioluminescent, imaging LOTUS-V does not require external light illumination. This allows bidirectional optogenetic control of cellular activity triggered by Channelrhodopsin2 and Halorhodopsin during voltage imaging. The other advantage of LOTUS-V is the robustness of a signal-to-background ratio (SBR) wherever it expressed, even in the specimens where autofluorescence from environment severely interferes fluorescence imaging. Through imaging of moving cardiomyocyte aggregates, we demonstrated the advantages of LOTUS-V in long-term imaging are attributable to the absence of phototoxicity, and photobleaching in bioluminescent imaging, combined with the ratiometric aspect of LOTUS-V design. Collectively LOTUS-V extends the scope of excitable cell control and simultaneous voltage phenotyping, which should enable applications in bioscience, medicine and pharmacology previously not possible

Maternal Prebiotic Ingestion Increased the Number of Fecal Bifidobacteria in Pregnant Women but Not in Their Neonates Aged One Month

Fructooligosaccharides (FOS) can selectively stimulate the growth of bifidobacteria. Here, we investigated the effect of maternal FOS ingestion on maternal and neonatal gut bifidobacteria. In a randomized, double-blind, placebo-controlled study, we administered 8 g/day of FOS or sucrose to 84 women from the 26th week of gestation to one month after delivery. The bifidobacteria count was detected using quantitative PCR in maternal (26 and 36 weeks of gestation) and neonatal (one month after delivery) stools. Maternal stool frequency was recorded from 24 to 36 weeks of gestation. The number of fecal Bifidobacterium spp. and Bifidobacterium longum in the FOS group was significantly higher than that in the placebo group at 36 weeks of gestation (2.7 × 1010/g vs. 1.1 × 1010/g and 2.3 × 1010/g vs. 9.7 × 109/g). In their neonates, these numbers did not differ between the groups. Also, stool frequency in the FOS group was slightly higher than that in the placebo group two weeks after the intervention (1.0 vs. 0.8 times/day), suggesting a potential constipation alleviation effect. In conclusion, the maternal FOS ingestion showed a bifidogenic effect in pregnant women but not in their neonates