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BackgroundConsidering the potential cumulative effects of repetitive head impact (HI) exposure, we need sensitive biomarkers to track short- and long-term effects. Circulating small extracellular vesicles (sEVs) (<200 nm) traffic biological molecules throughout the body and may have diagnostic value as biomarkers for disease. The purpose of this study was to identify the microRNA (miRNA) profile in circulating sEVs derived from human plasma following repetitive HI exposure.MethodsHealthy adult (aged 18–35 years) soccer players were randomly assigned to one of 3 groups: the HI group performed 10 standing headers, the leg impact group performed 10 soccer ball trapping maneuvers over 10 min, and the control group did not participate in any soccer drills. Plasma was collected before testing and 24 h afterward, and sEVs were isolated and characterized via nanoparticle tracking analysis. Next-generation sequencing was utilized to identify candidate miRNAs isolated from sEVs, and candidate microRNAs were analyzed via quantitative polymerase chain reaction. In silico target prediction was performed using TargetScan (Version 7.0; targetscan.org) and miRWalk (http://mirwalk.umm.uni-heidelberg.de/) programs, and target validation was performed using luciferase reporter vectors with a miR-7844-5p mimic in human embryonic kidney (HEK) 293T/17 cells.ResultsPlasma sEV concentration and size were not affected across time and group following repetitive HI exposure. After 24 h, the HI read count from next-generation sequencing showed a 4-fold or greater increase in miR-92b-5p, miR-423-5p, and miR-24-3p and a 3-fold or greater decrease in miR-7844-5p, miR-144-5p, miR-221-5p, and miR-22-3p. Analysis of quantitative polymerase chain reaction revealed that leg impact did not alter the candidate miRNA levels. To our knowledge, miR-7844-5p is a previously unknown miRNA. We identified 8 miR-7844-5p mRNA targets: protein phosphatase 1 regulatory inhibitor subunit 1B (PPP1R1B), LIM and senescent cell antigen-like domains 1 (LIMS1), autophagy-related 12 (ATG12), microtubule-associated protein 1 light chain 3 beta (MAP1LC3B), integrin subunit alpha-1 (ITGA1), mitogen-activated protein kinase 1 (MAPK1), glycogen synthase kinase 3β (GSK3β), and mitogen-activated protein kinase 8 (MAPK8).ConclusionCollectively, these data indicate repetitive HI exposure alters plasma sEV miRNA content, but not sEV size or number. Furthermore, for the first time we demonstrate that previously unknown miR-7844-5p targets mRNAs known to be involved in mitochondrial apoptosis, autophagy regulation, mood disorders, and neurodegenerative disease.  相似文献   
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Abstract

This study examined the effects of cognitive load experienced by e-learners as they negotiated the tasks required for successful participation within an asynchronous course room, specifically examining the relationship between measured cognitive load and the learners' confidence in completing their course. The results indicated that learner confidence, or more specifically self-efficacy, is the single most important factor in determining the success of e-learners. It appears that insufficient time was expended orienting learners to the virtual classrooms and to the technology necessary for participation.  相似文献   
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In this paper we discuss the background to this study in the development of the international MSc e‐Learning Multimedia and Consultancy. The aims of the study focus on the conditions for achieving communication, interaction and collaboration in open and flexible e‐learning environments. We present our theoretical framework that has informed the design of programme as a whole which is based on a socio‐constructivist perspective on learning. Our research is placed within an action research framework and we outline our position within the critical or emancipatory tradition and also our standpoint on the use of ICT in education. We discuss the design of the programme and also our pedagogical approach and describe in detail the particular context for this study. We report on the student experience of being learners on this module, their perceptions of what they have gained most from learning from and with each other and their responses to the various ways in which ‘scaffolding’ has been designed and implemented by the tutors. Finally we offer some reflections on the conditions for achieving well‐orchestrated interdependence in open and flexible e‐learning environments.  相似文献   
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National and international reform documents have forged blueprints for advancing science education. Coursework for preservice teachers needs to correspond to these documents by providing learning experiences that develop preservice teachers’ capabilities to plan and implement reform measures. Using a pretest–posttest design, responses from 59 2nd-year preservice teachers from the same university were compared after involvement in an elementary science pedagogy coursework. The survey, which was linked to the course outcomes (constructs) and multiple indicators, measured the preservice teachers’ perceptions of their development towards becoming elementary science teachers. A pretest–posttest survey linked to course outcomes can be employed to assess perceived pedagogical development of preservice teachers, which can inform further teaching practices for implementing science education reform agendas.  相似文献   
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Pearlette Louisy raises issues of pressing concern for the future of Caribbean education. Here, I elaborate on some of the dilemmas that she raises. Interwoven in this discussion are sketches of potentially positive scenarios in a globalising future.  相似文献   
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