71 research outputs found

    ATP released by intestinal bacteria limits the generation of protective IgA against enteropathogens

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    T cell dependent secretory IgA (SIgA) generated in the Peyer’s patches (PPs) of the small intestine shapes a broadly diverse microbiota that is crucial for host physiology. The mutualistic co-evolution of host and microbes led to the relative tolerance of host’s immune system towards commensal microorganisms. The ATP-gated ionotropic P2X7 receptor limits T follicular helper (Tfh) cells expansion and germinal center (GC) reaction in the PPs. Here we show that transient depletion of intestinal ATP can dramatically improve high-affinity IgA response against both live and inactivated oral vaccines. Ectopic expression of Shigella flexneri periplasmic ATP-diphosphohydrolase (apyrase) abolishes ATP release by bacteria and improves the specific IgA response against live oral vaccines. Antibody responses primed in the absence of intestinal extracellular ATP (eATP) also provide superior protection from enteropathogenic infection. Thus, modulation of eATP in the small intestine can affect highaffinity IgA response against gut colonizing bacteria

    Plasticity may change inputs as well as processes, structures, and responses

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    Significant work has documented neuroplasticity in development, demonstrating that developmental pathways are shaped by experience. Plasticity is often discussed in terms of the results of differences in input; differences in brain structures, processes, or responses reflect differences in experience. In this paper, I discuss how developmental plasticity also effectively changes input into the system. That is, structures and processes change in response to input, and those changed structures and processes influence future inputs. For example, plasticity may change the pattern of eye movements to a stimulus, thereby changing which part of the scene becomes the input. Thus, plasticity is not only seen in the structures and processes that result from differences in experience, but also is seen in the changes in the input as those structures and processes adapt. The systematic study of the nature of experience, and how differences in experience shape learning, can contribute to our understanding of neuroplasticity in general

    Persistence of self-injurious behaviour in autism spectrum disorder over 3 years: a prospective cohort study of risk markers

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    BackgroundThere are few studies documenting the persistence of self-injury in individuals with autism spectrum disorder (ASD) and consequently limited data on behavioural and demographic characteristics associated with persistence. In this longitudinal study, we investigated self-injury in a cohort of individuals with ASD over 3 years to identify behavioural and demographic characteristics associated with persistence.MethodsCarers of 67 individuals with ASD (Median age of individuals with ASD in years = 13.5, Interquartile Range = 10.00–17.00), completed questionnaires relating to the presence and topography of self-injury at T1 and three years later at T2. Analyses were conducted to evaluate the persistence of self-injury and to evaluate the behavioural and demographic characteristics associated with persistence of self-injury.ResultsAt T2 self-injurious behaviour had persisted in 77.8 % of individuals. Behavioural correlates of being non-verbal, having lower ability and higher levels of overactivity, impulsivity and repetitive behaviour, were associated with self-injury at both time points. Risk markers of impulsivity (p = 0.021) and deficits in social interaction (p = 0.026) at T1 were associated with the persistence of self-injury over 3 years.ConclusionsImpulsivity and deficits in social interaction are associated with persistent self-injury in ASD and thus may act as behavioural risk markers. The identification of these risk markers evidences a role for behaviour dysregulation in the development and maintenance of self-injury. The findings have clinical implications for proactive intervention; these behavioural characteristics may be utilised to identify ‘at risk’ individuals for whom self-injury is likely to be persistent and therefore those individuals for whom early intervention may be most warranted.<br/

    Absenteeism and the Use of Online Learning Modules

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    Absenteeism is an issue plaguing schools across the nation. A disruption in learning occurs when students miss valuable instruction due to illness or extended vacations. Many schools are looking at the use of online learning modules as a possible solution. Used in the post-secondary environment, online learning modules have the potential to deliver engaging and collaborative lessons on a 24-hour basis. This action research project examined whether middle school students were comfortable with receiving instructional materials from a learning module in an online format. Through the use of Web 2.0 tools, students provided evidence of understanding Hawaii Standard CTE.7-8.2.4 which deals with analyzing how skills and interests affect career choices. Data collection was in the form of pre and post online surveys and student reflections in an online blog. The research focused on the ease with which students were able to navigate an online module, comfort level using Web 2.0 tools to collaborate and motivational level while carrying out tasks. As a result of this study in a regular classroom, the researcher and others interested in the topic will now have a better understanding of the requirements in designing online learning to help absentee middle school students

    Cancer-specific defects in DNA repair pathways as targets for personalized therapeutic approaches

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    Defects in DNA repair pathways enable cancer cells to accumulate genomic alterations that contribute to their aggressive phenotype. However, tumors rely on residual DNA repair capacities to survive the damage induced by genotoxic stress. This dichotomy might explain why only isolated DNA repair pathways are inactivated in cancer cells. Accordingly, synergism has been observed between DNA-damaging drugs and targeted inhibitors of DNA repair. DNA repair pathways are generally thought of as mutually exclusive mechanistic units handling different types of lesions in distinct cell cycle phases. Recent preclinical studies, however, provide strong evidence that multifunctional DNA repair hubs, which are involved in multiple conventional DNA repair pathways, are frequently altered in cancer. We therefore propose that targeted anticancer therapies should not only exploit synthetic lethal interactions between two single genes but also consider alterations in DNA repair hubs. Such a network-based approach considerably increases the opportunities for targeting DNA repair-defective tumors

    Establishing Student Publication Seminars in Higher Education

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    A publication seminar is a course (lecture, seminar, project, etc.) during which students create material with the intent and infrastructure to publish it. The publication concept is broadly understood as ‘making the work publicly available’ and is not limited to publications via publishing houses or journals. This handbook results from the "Student Publication Seminars" project (2022-2023) and gives step-by-step instructions and provides checklists for instructors who want to make student course works publicly visible

    EinfĂŒhrung studentischer Publikationsseminare an Hochschulen

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    Ein Publikationsseminar ist eine Lehrveranstaltung (Vorlesung, Seminar, Projekt etc.), in der Studierende Material mit der Absicht und der Infrastruktur erstellen, es zu veröffentlichen. Das Konzept der Veršoffentlichung soll weitreichend als “die Arbeit öffentlich zugĂ€nglich machen” verstanden werden und ist nicht auf Veröffentlichungen ĂŒber Verlage oder Fachzeitschriften beschrĂ€nkt. In dieser Handreichung, die aus dem Projekt "Studentische Publikationsseminare" (2022-2023) entstanden ist, fassen wir Erfahrungen aus verschiedenen Lehrveranstaltungen zusammen und geben Hilfestellungen und Checklisten fĂŒr Lehrende, die es ihren Studierenden ermöglichen wollen, Seminararbeiten etc. öffentlich zu machen
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