100 research outputs found

    Defective Glycinergic Synaptic Transmission in Zebrafish Motility Mutants

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    Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Recently, in vivo analysis of glycinergic synaptic transmission has been pursued in zebrafish using molecular genetics. An ENU mutagenesis screen identified two behavioral mutants that are defective in glycinergic synaptic transmission. Zebrafish bandoneon (beo) mutants have a defect in glrbb, one of the duplicated glycine receptor (GlyR) β subunit genes. These mutants exhibit a loss of glycinergic synaptic transmission due to a lack of synaptic aggregation of GlyRs. Due to the consequent loss of reciprocal inhibition of motor circuits between the two sides of the spinal cord, motor neurons activate simultaneously on both sides resulting in bilateral contraction of axial muscles of beo mutants, eliciting the so-called ‘accordion’ phenotype. Similar defects in GlyR subunit genes have been observed in several mammals and are the basis for human hyperekplexia/startle disease. By contrast, zebrafish shocked (sho) mutants have a defect in slc6a9, encoding GlyT1, a glycine transporter that is expressed by astroglial cells surrounding the glycinergic synapse in the hindbrain and spinal cord. GlyT1 mediates rapid uptake of glycine from the synaptic cleft, terminating synaptic transmission. In zebrafish sho mutants, there appears to be elevated extracellular glycine resulting in persistent inhibition of postsynaptic neurons and subsequent reduced motility, causing the ‘twitch-once’ phenotype. We review current knowledge regarding zebrafish ‘accordion’ and ‘twitch-once’ mutants, including beo and sho, and report the identification of a new α2 subunit that revises the phylogeny of zebrafish GlyRs

    Expanding the Repertoire of Optogenetically Targeted Cells with an Enhanced Gene Expression System

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    Optogenetics has been enthusiastically pursued in recent neuroscience research, and the causal relationship between neural activity and behavior is becoming ever more accessible. Here, we established knockin-mediated enhanced gene expression by improved tetracycline-controlled gene induction (KENGE-tet) and succeeded in generating transgenic mice expressing a highly light-sensitive channelrhodopsin-2 mutant at levels sufficient to drive the activities of multiple cell types. This method requires two lines of mice: one that controls the pattern of expression and another that determines the protein to be produced. The generation of new lines of either type readily expands the repertoire to choose from. In addition to neurons, we were able to manipulate the activity of nonexcitable glial cells in vivo. This shows that our system is applicable not only to neuroscience but also to any biomedical study that requires understanding of how the activity of a selected population of cells propagates through the intricate organic systems

    A patient with hypereosinophilic syndrome that manifested with acquired hemophilia and elevated IgG4: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Hypereosinophilic syndrome is defined as a prolonged state (more than six months) of eosinophilia (greater than 1500 cells/μL), without an apparent etiology and with end-organ damage. Hypereosinophilic syndrome can cause coagulation abnormalities. Among hypereosinophilic syndrome types, the lymphocytic variant (lymphocytic hypereosinophilic syndrome) is derived from a monoclonal proliferation of T lymphocytes. Here, we describe the case of a patient with lymphocytic hypereosinophilic syndrome who presented with a coagulation abnormality. To the best of our knowledge, this is the first such report including a detailed clinical picture and temporal cytokine profile.</p> <p>Case presentation</p> <p>A 77-year-old Japanese man presented to our facility with massive hematuria and hypereosinophilia (greater than 2600 cells/μl). His eosinophilia first appeared five years earlier when he developed femoral artery occlusion. He manifested with multiple hematomas and prolonged activated partial thromboplastin time. His IgG4 level was remarkably elevated (greater than 2000 mg/dL). Polymerase chain reaction tests of peripheral blood and bone marrow identified lymphocytic hypereosinophilic syndrome. His prolonged activated partial thromboplastin time was found to be due to acquired hemophilia. Glucocorticoids suppressed both the hypereosinophilia and coagulation abnormality. However, tapering of glucocorticoids led to a relapse of the coagulation abnormality alone, without eosinophilia. Tumor necrosis factor α, interleukin-5, and/or eotaxin-3 may have caused the hypereosinophilia, and interleukin-10 was correlated with the coagulation abnormality.</p> <p>Conclusions</p> <p>To the best of our knowledge, this is the first case in which lymphocytic hypereosinophilic syndrome and IgG4-related disease have overlapped. In addition, our patient is only the second case of hypereosinophilic disease that manifested with acquired hemophilia. Our patient relapsed with the coagulation abnormality alone, without eosinophilia. This report shows that the link between eosinophilia, IgG4, and clinical manifestations is not simple and provides useful insight into the immunopathology of hypereosinophilic syndrome and IgG4-related disease.</p

    新見公立短期大学在学生の受験動向(創刊二十五周年記念号)

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    2004年(平成16年)4月、本学では、将来構想委員会が「新見公立短期大学在学生アンケート(志望動向)」による在学生の受験志望動向に関する調査を行った。本報告は、その調査結果の集計をもとに、2002年度に本学で行われた「第1回学生生活実態調査」(学生生活委員会および自己点検・評価委員会による)集計と比較し、在学生の受験動向をまとめたものである。その結果、全学的に本学第一志望の学生の占める割合が増加していること、看護学科で国公立四年制大学志望者が増加していることが分かった。そして、公立・免許資格・専門職養成の三大動機が本学志望の特徴であることが明らかになった。The planning committee of Niimi College investigated the entrance examination trends of our college in April, 2004. An investigation on students\u27 life was done by the student affairs committee and the self evaluation committee in Niimi College in 2002. This report compares the two investigations, and reveals the students\u27 trends of Niimi College\u27s entrance examination. As a result of an investigation on entrance examination to Niimi College, we came to understand that the number of students who wanted to come to Niimi College as their first choice is increasing in all the departments, and that in the Department of Nursing, the number of students who wanted to go to a four-year national university is increasing. We have also clarified that there are the three major motives:1) being public, 2) providing license qualifications, and 3) being a professional training facility

    成人看護学実習における看護技術経験の実態

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    本研究の目的は、看護技術チェックリストを用いて成人看護学実習における看護技術の経験状況を明らかにし、成人看護学における臨地実習での教育・指導内容について検討することである。成人看護学実習Ⅰ(急性期実習)・Ⅱ(慢性期実習)を履修した学生に対し、看護技術チェックリスト90項目を用いて実習中の看護技術経験を調査した結果、急性期実習、慢性期実習ともに80%以上経験できた看護技術は、「快適な病床環境を作る」、「食事摂取状況のアセスメント」、「栄養状態のアセスメント」、「バイタルサイン測定」、「一般状態の変化」、「系統的な症状の観察」、「測定値・症状等からのアセスメント」、「スタンダード・プリコーションに基づく手洗い」、「防護用具の装着」、「療養病床を安全に整える」、「転倒・転落・外傷予防」の11項目であった。未経験が50%以上の項目は急性期実習で51項目、慢性期実習で64項目であった。臨地実習において学生が看護技術の経験を増やすことに限界はあるが、少ない経験からでも最大限の学びが得られるよう関わることや、看護技術の経験の機会を逃さない関わりが教員には必要であると示唆された

    Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

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    Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

    Is “less calories and more exercise” enough to prevent hypertension, diabetes, or dyslipidemia in individuals undergoing health checkups? A 5-year retrospective cohort study

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     Medical professionals generally use “less calories and more exercise” as advice to patients with lifestyle-related diseases. This retrospective cohort study aimed to determine suitable lifestyle modification strategies to prevent hypertension, diabetes, or dyslipidemia in individuals who participated in a medical health check. Health check data of 24, 244 individuals who underwent a specific health check at a health service organization in Fukuyama, Japan from 2011 to 2015 were compared and the association between current lifestyle and onset of hypertension, diabetes, or dyslipidemia in the next 5 years was assessed via Cox proportional hazard model. Current daily alcohol consumption was associated with the onset of hypertension in the next 5 years. Onset of diabetes was related to current smoking. In addition, “eating quickly” was related to diabetes onset in the next 5 years. Given that these lifestyle habits were associated with the onset of the diseases after adjustment with BMI, more appropriate recommendations for lifestyle modification should be considered at health guidance

    IPS cells: a game changer for future medicine

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    Abstract The induced pluripotent stem cell (iPSC) technology is instrumental in advancing the fields of disease modeling and cell transplantation. We herein discuss the various issues regarding disease modeling and cell transplantation presented in previous reports, and also describe new iPSC-based medicine including iPSC clinical trials. In such trials, iPSCs from patients can be used to predict drug responders/non-responders by analyzing the efficacy of the drug on iPSC-derived cells. They could also be used to stratify patients after actual clinical trials, including those with sporadic diseases, based on the drug responsiveness of each patient in the clinical trials. iPSC-derived cells can be used for the identification of response markers, leading to increased success rates in such trials. Since iPSCs can be used in micromedicine for drug discovery, and in macromedicine for actual clinical trials, their use would tightly connect both micro-and macromedicine. The use of iPSCs in disease modeling, cell transplantation, and clinical trials could therefore lead to significant changes in the future of medicine

    A multicenter, randomized, controlled study of the use of nutritional supplements containing collagen peptides to facilitate the healing of pressure ulcers

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    Since collagen peptide stimulates fibroblast growth in skin, it may accelerate the healing of pressure ulcers. Therefore, the purpose of our study was to verify whether the intake of collagen peptides in the form of a supplement drink facilitates the healing of pressure ulcers. We conducted a multicenter, randomized, controlled trial in patients with pressure ulcers. Patients were randomized into 3 groups at a 1:1:1 ratio; control group (usual care), collagen peptide-containing drink group and arginine-containing drink group. The DESIGN-R tool was used to assess healing of pressure ulcers, and nutritional status was measured for 4 weeks while consuming the usual daily meals. Out of 66 patients randomized, 51 patients were analyzed, since 15 patients were excluded from the final analysis. The total DESIGN-R score in patients who received the collagen peptide-containing drink (n = 18) was significantly lower than that in patients in the control group (n = 16) after 2 weeks as well as at the final value. However, the DESIGN-R score in the arginine-containing drink group (n = 17) did not show difference from the control group. There was no significant difference in nutrition status among the 3 groups through the study. Our results indicated that a supplemental addition of the collagen peptide-containing drink to the usual meal facilitated pressure ulcer healing, since the collagen peptide-containing drink led to more changes in the DESIGN-R scores
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