112 research outputs found

    The Intensity of Satellite Reflections in Electron Diffraction Patterns from Evaporated Alloy Films with CuAu II Type Superstructure

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    In order to elucidate the origin of satellite reflections flanking the direct spot in the electron diffraction pattern of a single crystal evaporated film with CuAu II type superlattice, the peak as well as integrated intensities have been measured as functions of the wavelength of electrons corresponding to the accelerating voltage from 75 to 280KV. It has been revealed that the intensity of the satellite in question relative to a fundamental reflection consists of two parts, a major part which depends on the wavelength in such a way as predicted by the theory of multiple reflection, and the other minor part which is independent of the wavelength. The existence of the latter part shows that the reflection is not a forbidden one and, therefore, a lattice modulation accompanies the regular anti-phase structure. Fourier potential due to this lattice modulation, V_s, is estimated to be in the order of one tenth the magnitude of V_ Some consideration concerning the nature of the modulation is given by comparing the results of electron and X-ray diffraction studies

    Decreased renal accumulation of aminoglycoside reflects defective receptor-mediated endocytosis in cystic fibrosis and Dent's disease

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    The clinical use of aminoglycoside (AG) antibiotics is limited by their renal toxicity, which is caused by drug accumulation in proximal tubule (PT) cells. Clinical studies reported that renal clearance of AG is enhanced in cystic fibrosis (CF) patients, which might reflect the role of CFTR in PT cell endocytosis. In order to assess the role of chloride transporters on the renal handling of AG, we investigated gentamicin uptake and renal accumulation in mice lacking functional CFTR (Cftr ∆F/∆F) or knock-out for the Cl−/H+ exchanger ClC-5 (Clcn5 Y/− ). The latter represent a paradigm of PT dysfunction and defective receptor-mediated endocytosis. As compared with controls, Cftr ∆F/∆F and Clcn5 Y/− mice showed a 15% to 85% decrease in gentamicin accumulation in the kidney, respectively, in absence of renal failure. Studies on primary cultures of Cftr ∆F/∆F and Clcn5 Y/− mouse PT cells confirmed the reduction in gentamicin uptake, although colocalization with endosomes and lysosomes was maintained. Quantification of endocytosis in PT cells revealed that gentamicin, similar to albumin, preferentially binds to megalin. The functional loss of ClC-5 or CFTR was reflected by a decrease of the endocytic uptake of gentamicin, with a more pronounced effect in cells lacking ClC-5. These results support the concept that CFTR, as well as ClC-5, plays a relevant role in PT cell endocytosis. They also demonstrate that the functional loss of these two chloride transporters is associated with impaired uptake of AG in PT cells, reflected by a decreased renal accumulation of the dru

    Tissue-specific splicing regulator Fox-1 induces exon skipping by interfering E complex formation on the downstream intron of human F1γ gene

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    Fox-1 is a regulator of tissue-specific splicing, via binding to the element (U)GCAUG in mRNA precursors, in muscles and neuronal cells. Fox-1 can regulate splicing positively or negatively, most likely depending on where it binds relative to the regulated exon. In cases where the (U)GCAUG element lies in an intron upstream of the alternative exon, Fox-1 protein functions as a splicing repressor to induce exon skipping. Here we report the mechanism of exon skipping regulated by Fox-1, using the hF1γ gene as a model system. We found that Fox-1 induces exon 9 skipping by repressing splicing of the downstream intron 9 via binding to the GCAUG repressor elements located in the upstream intron 8. In vitro splicing analyses showed that Fox-1 prevents formation of the pre-spliceosomal early (E) complex on intron 9. In addition, we located a region of the Fox-1 protein that is required for inducing exon skipping. Taken together, our data show a novel mechanism of how RNA-binding proteins regulate alternative splicing

    Initial Results of Robotic Surgery for Primary Lung Cancer: Feasibility, Safety and Learning Curve

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    [Background] At the end of 2016, robot-assisted thoracoscopic surgery (RATS) was still not covered by Japanese national health insurance. Therefore, few institutions in Japan perform RATS and even fewer have reported procedures as they occurred earlier. So, we decided to focus on the initial results of RATS for primary lung cancer. [Methods] We retrospectively reviewed 44 patients who underwent RATS for primary lung cancer from January 2011 to August 2016. After mastering the initial procedure, we introduced a completely portal robotic pulmonary resection procedure using a carbon dioxide insufflation system. Cases were divided into 2 groups: the early period (20 cases) and the later period (24 cases). [Results] There was no case of conversion to video-assisted thoracoscopic surgery or thoracotomy. In the 44 cases of primary lung cancer, median operating time was 239.5 min, console time was 179 min, blood loss was 10 mL, drainage period was 2 days, morbidity of Grade 2 or more (Clavien-Dindo classification) was 18.2%, morbidity of Grade 3 or more was only 4.6%, and there was no 30-day mortality. Median operating and console times were significantly shorter in the later period (215 min and 159.5 min, respectively) than in the initial period (300.5 min and 228 min, respectively). Median blood loss was significantly lower in the later period (5 mL) than in the initial period (50 mL). Fiveyear overall and disease-free survival rates were 100% and 88.9%, respectively. [Conclusion] RATS for primary lung cancer is feasible and safe, has a faster learning curve, and provides satisfactory. Studies with longer follow-ups and larger numbers of cases are necessary

    DAZL Relieves miRNA-Mediated Repression of Germline mRNAs by Controlling Poly(A) Tail Length in Zebrafish

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    BACKGROUND:During zebrafish embryogenesis, microRNA (miRNA) miR-430 contributes to restrict Nanos1 and TDRD7 to primordial germ cells (PGCs) by inducing mRNA deadenylation, mRNA degradation, and translational repression of nanos1 and tdrd7 mRNAs in somatic cells. The nanos1 and tdrd7 3'UTRs include cis-acting elements that allow activity in PGCs even in the presence of miRNA-mediated repression. METHODOLOGY/PRINCIPAL FINDINGS:Using a GFP reporter mRNA that was fused with tdrd7 3'UTR, we show that a germline-specific RNA-binding protein DAZ-like (DAZL) can relieve the miR-430-mediated repression of tdrd7 mRNA by inducing poly(A) tail elongation (polyadenylation) in zebrafish. We also show that DAZL enhances protein synthesis via the 3'UTR of dazl mRNA, another germline mRNA targeted by miR-430. CONCLUSIONS/SIGNIFICANCE:Our present study indicated that DAZL acts as an "anti-miRNA factor" during vertebrate germ cell development. Our data also suggested that miRNA-mediated regulation can be modulated on specific target mRNAs through the poly(A) tail control

    Time-resolved serial femtosecond crystallography reveals early structural changes in channelrhodopsin

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    X線自由電子レーザーを用いて、光照射によるチャネルロドプシンの構造変化の過程を捉えることに成功. 京都大学プレスリリース. 2021-03-26.Channelrhodopsins (ChRs) are microbial light-gated ion channels utilized in optogenetics to control neural activity with light . Light absorption causes retinal chromophore isomerization and subsequent protein conformational changes visualized as optically distinguished intermediates, coupled with channel opening and closing. However, the detailed molecular events underlying channel gating remain unknown. We performed time-resolved serial femtosecond crystallographic analyses of ChR by using an X-ray free electron laser, which revealed conformational changes following photoactivation. The isomerized retinal adopts a twisted conformation and shifts toward the putative internal proton donor residues, consequently inducing an outward shift of TM3, as well as a local deformation in TM7. These early conformational changes in the pore-forming helices should be the triggers that lead to opening of the ion conducting pore

    仙台大学学生の体格および体力

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    The purpose of this study was to investigate the characteristics of physique and physical fitness of the students in Sendai college. The measurements of physique consisted of body weight, chest girth and sitting height. The test measurements of physical fitness consisted of shuttle run, sit-ups, succession of vertical jumps (5 times), floor push-ups and standing long jumps. The results were as follows: 1) The physique and physical fitness of the students in Sendai college differed significantly from those of the same aged Japanese. 2) The stature and body weight of all students were the same, but the chest girth and sitting height of them found to have increased a little from 1974 to 1977, but shuttle run decreased. 3) The stature, body weight, chest girth of the freshmen were found to have increased year by year, but the chest girth of them decreased. Sit-ups, floor push-ups and standing long jumps of the freshmen were found to have increased, but shuttle run of them decreased from 1974 to 1977. 4) As for the change of the physique and the physical fitness with which the students entered in 1973, the stature and body weight were found to have increased 0.6 cm, 2.9kg, respectively, but the chest girth and sitting height were found not to have changed. The 4 measurements except shuttle run were found to have increased
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