112 research outputs found

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

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    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

    The Characteristics of Apathy in University Students and Issues in Education The Effect on Clinical Training of Attitude and Results (GPA) Prior to Clinical Training, and Forecast Training Results

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    Background: In recent years, the apathetic attitude of students has been a frequent problem in clinical training. Objectives: To consider the effects on students' results for the clinical training element of their course of their attitude and grade point average (GPA) prior to clinical training, and to examine educational issues within the university. Method: The study focused on 43 fourthyear students in this university's Department of Occupational Therapy. In order to survey students' attitudes and results prior to undertaking clinical training, we looked at three criteria: their GPA at the university prior to clinical training, an Apathy scale and a locus of control. Thereafter, using Spearman rank order correlations and multiple logistic regression analysis, we undertook a comparison, at a significance level of 5%, of the relationship between attitude and results prior to the two eight-week periods of clinical training (Clinical Training III) undertaken by the students. Results: With regard to the training results in the field of mental disability, there was a significant correlation between GPA and Apathy. In particular, those with a sense of physical fatigue and those suffering from a disrupted lifestyle tended to have bad results for their training in this field. In the field of geriatric care as well, there was a significant correlation where those with a disrupted lifestyle were concerned. On the other hand, unlike in other fields, results for training in the field of physical disability showed a significant correlation with regard to lack of effort. Looking at the training by period, GPA had an effect on results for the first period of training, but no correlation was seen with regard to results for the second period. On the other hand, the locus of control and Apathy total were related to results for the second period of training. Multiple logistic regression analysis showed us that it was possible to predict the probability that results for training in the field of mental disability would be in the lower two groups from the rise in the total for lifestyle disruption prior to clinical training (odds ratio 2.40; 95% confidence interval, 1.03~5.57, p=0.04). Furthermore, we discovered that it was possibly to predict the probability that results for training in the field of mental disability would be in the top group from the rise in the total for physical fatigue prior to clinical training (odds ratio 0.62; 95% confidence interval, 0.40~0.95, p=0.03). Conclusions: Items where there was a correlation with clinical training results can generally be said to be expressions of attitude or drive. In other words, even if the low expression of attitude or drive can be covered up in the first period of training by academic work completed prior to the training, it is likely that a apathetic attitude will have an effect on results for clinical training during the second period. The point on which we would particularly like to focus is the fact that, based on the results of multiple logistic regression analysis, we were able to calculate that it was possible to predict results for training in the field of mental disability from the totals for lifestyle disruption and physical fatigue prior to clinical training

    TNFRSF1B A1466G genotype is predictive of clinical efficacy after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma

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    <p>Abstract</p> <p>Background</p> <p>Currently definitive 5-fluorouracil (5-FU)/cisplatin (CDDP) -based chemotherapy is recognized as one of the most promising treatments for esophageal cancer. A series of studies performed found genetic polymorphisms and the plasma concentration of 5-FU to be predictive of acute severe toxicities and clinical response. Genetic polymorphisms of <it>tumor necrosis factor (TNF) -α </it>and its surface receptors, <it>TNFRSF1A </it>and <it>TNFRSF1B </it>have been examined in terms of susceptibility to various cancers. In this study, genetic polymorphisms of <it>TNFRSF1B </it>gene were evaluated Japanese esophageal squamous cell carcinoma (ESCC) patients treated with the definitive 5-FU/CDDP-based chemoradiotherapy and their predictive values of prognosis or severe acute toxicities were assessed.</p> <p>Methods</p> <p>Forty-six patients with ESCC were treated with the definitive 5-FU/CDDP-based chemoradiotherapy, one course of which consisted of the continuous infusion of 5-FU for days 1-5 and 8-12, the infusion of CDDP on days 1 and 8, and the radiation at 2 Gy/day on days 1-5, 8-12, and 15-19, with a second course repeated after 2-week interval. Genetic polymorphisms of a TNF-α receptor <it>TNFRSF1B </it>gene were determined by a TaqMan<sup>® </sup>MGB probe-based polymerase chain reaction.</p> <p>Results</p> <p>The genotype of <it>TNFSR1B </it>A1466G, but not M196R/T587G or C1493T, was found to be predictive of clinical response, i.e., a complete response or not (p = 0.040). Clinical response was predicted by tumor size (p = 0,002), lymph node metastasis (p = 0.007), distant metastasis (p = 0.001) and disease stage (p < 0.001), but <it>TNFRSF1B </it>A1466G genotype was independent of these factors.</p> <p>Conclusions</p> <p>Genetic polymorphism of <it>TNFRSF1B </it>A1466G was found to be predictive response in Japanese ESCC patients with a definitive 5-FU/CDDP-based chemoradiotherapy. Further clinical investigation with a large number of patients or experiments in vitro should be performed to assess the predictive value of <it>TNFRSF1B </it>A1466G genotype after chemoradiotherapy.</p

    成熟T細胞の生存はHOIPを介するシグナルに依存する

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    T cell development in the thymus is controlled by a multistep process. The NF-κB pathway regulates T cell development as well as T cell activation at multiple differentiation stages. The linear ubiquitin chain assembly complex (LUBAC) is composed of Sharpin, HOIL-1L and HOIP, and it is crucial for regulating the NF-κB and cell death pathways. However, little is known about the roles of LUBAC in T-cell development and activation. Here, we show that in T-HOIPΔlinear mice lacking the ubiquitin ligase activity of LUBAC, thymic CD4+ or CD8+ T cell numbers were markedly reduced with severe defects in NKT cell development. HOIPΔlinear CD4+ T cells failed to phosphorylate IκBα and JNK through T cell receptor-mediated stimulation. Mature CD4+ and CD8+ T cells in T-HOIPΔlinear mice underwent apoptosis more rapidly than control T cells, and it was accompanied by lower CD127 expression on CD4+CD24low and CD8+CD24low T cells in the thymus. The enforced expression of CD127 in T-HOIPΔlinear thymocytes rescued the development of mature CD8+ T cells. Collectively, our results showed that LUBAC ligase activity is key for the survival of mature T cells, and suggest multiple roles of the NF-κB and cell death pathways in activating or maintaining T cell-mediated adaptive immune responses

    Psychiatric intervention and repeated admission to emergency centres due to drug overdose

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    Self-harm, with or without suicidal intent, substantially increases the risk of future suicide and is known to be the strongest predictor of completed suicide. Furthermore, repetition of self-harm is common: 16% of patients who self-harmed were found to repeat a similar episode within 1 year. Repetition of self-harm increases the risk of completed suicide. One study found overdose to be the most prevalent type of suicide attempt that required admission, and approximately 80% of self-harm episodes have been reported to involve overdose. It is therefore necessary to prevent the repetition of self-harm by drug overdose. According to clinical guidelines on the management of self-harm published in 2004, it is recommended that every patient presenting to hospital with self-harm should undergo a psychosocial assessment by specialists before being discharged. Despite this recommendation, some studies have found that many patients, especially those with repeated self-harm did not actually receive such assessments. That would suggest that the guideline has not been widely used – possibly because it was not based on firm evidence. There is a lack of data on the influence of psychosocial assessments on preventing repetition of self-harm. Some studies have suggested that such assessments do have an influence, but they were based on a small sample size or on a small number of highly advanced institutions. The present study focused on patients with drug overdose who were admitted to emergency centres. Using a national in-patient database in Japan, it aimed to investigate whether psychiatric intervention before discharge was associated with reduced patient readmissions with drug overdose.UTokyo Research掲載「過量服薬による入院患者と精神科医による診察の関係」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/psychiatric-intervention-and-repeated-emergency-admission-due-to-drug-overdose.htmlUTokyo Research "Psychiatric intervention and repeated emergency admission due to drug overdose" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/psychiatric-intervention-and-repeated-emergency-admission-due-to-drug-overdose.htm

    Effects of Hormones on Cultivation of Tricholoma matsutake Mycelia

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    A mixture of callus of Akamatsu and mycelium of Tricholoma matsutake was obtained from roots of it with MS medium containing 0.01μM of 2, 4-D and 0.1μM of kinetin. Colony, which formed polymer of mycelia of T. matsutake, was obtained with MS medium containing 0.01μM of IAA and 0.01μM of kinetin. Therefore, it may be possible to cultivate T. matsutake by means of using hormones such as IAA and kinetin on the sawdust medium
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