7,167 research outputs found

    Human olfactory mesenchymal stromal cell transplants promote remyelination and earlier improvement in gait co-ordination after spinal cord injury

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    Autologous cell transplantation is a promising strategy for repair of the injured spinal cord. Here we have studied the repair potential of mesenchymal stromal cells isolated from the human olfactory mucosa after transplantation into a rodent model of incomplete spinal cord injury. Investigation of peripheral type remyelination at the injury site using immunocytochemistry for P0, showed a more extensive distribution in transplanted compared with control animals. In addition to the typical distribution in the dorsal columns (common to all animals), in transplanted animals only, P0 immunolabelling was consistently detected in white matter lateral and ventral to the injury site. Transplanted animals also showed reduced cavitation. Several functional outcome measures including end-point electrophysiological testing of dorsal column conduction and weekly behavioural testing of BBB, weight bearing and pain, showed no difference between transplanted and control animals. However, gait analysis revealed an earlier recovery of co-ordination between forelimb and hindlimb stepping in transplanted animals. This improvement in gait may be associated with the enhanced myelination in ventral and lateral white matter, where fibre tracts important for locomotion reside. Autologous transplantation of mesenchymal stromal cells from the olfactory mucosa may therefore be therapeutically beneficial in the treatment of spinal cord injury

    Heat shock factor 1 regulates lifespan as distinct from disease onset in prion disease

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    Prion diseases are fatal, transmissible, neurodegenerative diseases caused by the misfolding of the prion protein (PrP). At present, the molecular pathways underlying prion-mediated neurotoxicity are largely unknown. We hypothesized that the transcriptional regulator of the stress response, heat shock factor 1 (HSF1), would play an important role in prion disease. Uninoculated HSF1 knockout (KO) mice used in our study do not show signs of neurodegeneration as assessed by survival, motor performance, or histopathology. When inoculated with Rocky Mountain Laboratory (RML) prions HSF1 KO mice had a dramatically shortened lifespan, succumbing to disease ≈20% faster than controls. Surprisingly, both the onset of home-cage behavioral symptoms and pathological alterations occurred at a similar time in HSF1 KO and control mice. The accumulation of proteinase K (PK)-resistant PrP also occurred with similar kinetics and prion infectivity accrued at an equal or slower rate. Thus, HSF1 provides an important protective function that is specifically manifest after the onset of behavioral symptoms of prion disease

    Visual Mapping With Magnetoencephalography: An Update on the Current State of Clinical Research and Practice With Considerations for Clinical Practice Guidelines

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    Using visual evoked fields (VEFs) to differentiate healthy, normal brain function from dysfunctional cortex has been demonstrated to be both valid and reliable. Currently, VEFs are widely implemented to guide intracranial surgeries for epilepsy and brain tumors. There are several areas of possible future clinical use of VEFs, including early identification of disorders, such as multiple sclerosis, Parkinson\u27s disease, stroke, and human immunodeficiency virus-associated neurocognitive disorders. These studies have suggested that VEFs could be used to study disease pathophysiology or as a biomarker for early identification of a disorder. The current clinical practice guidelines of the American Clinical Magnetoencephalography Society for VEFs are sufficient. At this time, VEFs should be used clinically to identify visual cortex and potentially tailor surgical resections

    Biomarker Exploration in Human Peripheral Blood Mononuclear Cells for Monitoring Sulforaphane Treatment Responses in Autism Spectrum Disorder

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    Autism Spectrum Disorder (ASD) is one of the most common neurodevelopmental disorders with no drugs treating the core symptoms and no validated biomarkers for clinical use. The multi-functional phytochemical sulforaphane affects many of the biochemical abnormalities associated with ASD. We investigated potential molecular markers from three ASD-associated physiological pathways that can be affected by sulforaphane: redox metabolism/oxidative stress; heat shock response; and immune dysregulation/inflammation, in peripheral blood mononuclear cells (PBMCs) from healthy donors and patients with ASD. We first analyzed the mRNA levels of selected molecular markers in response to sulforaphane ex vivo treatment in PBMCs from healthy donors by real-time quantitative PCR. All of the tested markers showed quantifiability, accuracy and reproducibility. We then compared the expression levels of those markers in PBMCs taken from ASD patients in response to orally-delivered sulforaphane. The mRNA levels of cytoprotective enzymes (NQO1, HO-1, AKR1C1), and heat shock proteins (HSP27 and HSP70), increased. Conversely, mRNA levels of pro-inflammatory markers (IL-6, IL-1beta, COX-2 and TNF-alpha) decreased. Individually none is sufficiently specific or sensitive, but when grouped by function as two panels, these biomarkers show promise for monitoring pharmacodynamic responses to sulforaphane in both healthy and autistic humans, and providing guidance for biomedical interventions

    The role of perceived source location in auditory stream segregation: separation affects sound organization, common fate does not

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    The human auditory system is capable of grouping sounds originating from different sound sources into coherent auditory streams, a process termed auditory stream segregation. Several cues can inïŹ‚uence auditory stream segregation, but the full set of cues and the way in which they are integrated is still unknown. In the current study, we tested whether auditory motion can serve as a cue for segregating sequences of tones. Our hypothesis was that, following the principle of common fate, sounds emitted by sources moving together in space along similar trajectories will be more likely to be grouped into a single auditory stream, while sounds emitted by independently moving sources will more often be heard as two streams. Stimuli were derived from sound recordings in which the sound source motion was induced by walking humans. Although the results showed a clear effect of spatial separation, auditory motion had a negligible inïŹ‚uence on stream segregation. Hence, auditory motion may not be used as a primitive cue in auditory stream segregation

    A Matter of Priorities: Effects of Increased Opportunities for Extracurricular and Non-Traditional Learning Experiences on Student Time Management and Attitudes

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    Many schools are emphasizing non-traditional and extracurricular learning experiences for undergraduate engineering students. These include activities such as incorporating servicelearning projects into the classroom, involving students in design competitions (e.g., solar car, formula car races), and promoting involvement in traditional campus organizations. Often this emphasis is in response to changes in ABET requirements, desires of future employers, and needs to improve student retention. What are the effects of emphasizing these sorts of activities on student attitudes and time management decisions? We examine the influences on students\u27 priorities for allocating their time and their perceptions of the relative importance of available activities, especially traditional coursework. We present data relating key personality and motivational factors to patterns of student social involvement, organizational commitment, academic performance, and work habits and attitudes. Implications for educators and potential cost-benefit trade-offs for particular student subpopulations are also presented

    Chromosome Abnormalities and Repeated Abortion: A Preliminary Report

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    In view of the increased frequency of chromosome rearrangements demonstrated in these couples and the importance of counseling for future pregnancies, it would be wise to consider cytogenetic evaluation when all other probable causes for recurrent abortion have been ruled out

    Legal Ethics in the Digital Age

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    Ms. deMaine\u27s contribution to the seminar is: Legal Ethics in the Digital Agehttps://www.repository.law.indiana.edu/facbooks/1218/thumbnail.jp

    Chimpanzees demonstrate individual differences in social information use

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    Studies of transmission biases in social learning have greatly informed our understanding of how behaviour patterns may diffuse through animal populations, yet within-species inter-individual variation in social information use has received little attention and remains poorly understood. We have addressed this question by examining individual performances across multiple experiments with the same population of primates. We compiled a dataset spanning 16 social learning studies (26 experimental conditions) carried out at the same study site over a 12-year period, incorporating a total of 167 chimpanzees. We applied a binary scoring system to code each participant’s performance in each study according to whether they demonstrated evidence of using social information from conspecifics to solve the experimental task or not (Social Information Score—‘SIS’). Bayesian binomial mixed effects models were then used to estimate the extent to which individual differences influenced SIS, together with any effects of sex, rearing history, age, prior involvement in research and task type on SIS. An estimate of repeatability found that approximately half of the variance in SIS was accounted for by individual identity, indicating that individual differences play a critical role in the social learning behaviour of chimpanzees. According to the model that best fit the data, females were, depending on their rearing history, 15–24% more likely to use social information to solve experimental tasks than males. However, there was no strong evidence of an effect of age or research experience, and pedigree records indicated that SIS was not a strongly heritable trait. Our study offers a novel, transferable method for the study of individual differences in social learning
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