429 research outputs found

    The essential role of AMPA receptor GluR2 subunit RNA editing in the normal and diseased brain

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    α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are comprised of different combinations of GluA1–GluA4 (also known asGluR1–GluR4 and GluR-A to GluR-D) subunits. The GluA2 subunit is subject to RNA editing by the ADAR2 enzyme, which converts a codon for glutamine (Gln; Q), present in the GluA2 gene, to a codon for arginine (Arg; R) found in the mRNA. AMPA receptors are calcium (Ca2+)-permeable if they contain the unedited GluA2(Q) subunit or if they lack the GluA2 subunit. While most AMPA receptors in the brain contain the edited GluA2(R) subunit and are therefore Ca2+-impermeable, recent evidence suggests that Ca2+-permeable AMPA receptors are important in synaptic plasticity, learning, and disease. Strong evidence supports the notion that Ca2+-permeable AMPA receptors are usually GluA2-lacking AMPA receptors, with little evidence to date for a significant role of unedited GluA2 in normal brain function. However, recent detailed studies suggest that Ca2+-permeable AMPA receptors containing unedited GluA2 do in fact occur in neurons and can contribute to excitotoxic cell loss, even where it was previously thought that there was no unedited GluA2.This review provides an update on the role of GluA2 RNA editing in the healthy and diseased brain and summarizes recent insights into the mechanisms that control this process. We suggest that further studies of the role of unedited GluA2 in normal brain function and disease are warranted, and that GluA2 editing should be considered as a possible contributing factor when Ca2+-permeable AMPA receptors are observed

    It\u27s not as thick as it looks: Unpacking the rehearsal practices of theatre professionals and the significance for the teaching of reading and writing

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    The purpose of my study was to identify and describe the components of theatre rehearsal and their implications for the teaching of reading and writing. Using qualitative methods of inquiry such as direct and participant observation and group and individual interviews, I documented the rehearsal process and literacy practices of members of a professional theatre company that performs only in academic environments. In analyzing the data I used Anderson and Jack\u27s strategies for listening and determined that there are four major components of theatre rehearsal: chunking (the breaking down of the script into smaller, more manageable pieces), repetition (the constant, purposeful repeating of the text), encouragement (the acknowledgement of the actor\u27s effort), and response (the verbal or non-verbal reaction to the other three components). These components provide opportunities for collaboration and discussion; they provide time to think about and discuss the choices being made; and they provide opportunities to use other tools and strategies such as visualization, inquiry or exploration, and self-evaluation. I believe using these rehearsal strategies to teach reading and writing can provide the same opportunities for our students. There is much discussion in the field of education about creating communities of learners. Rehearsal can help us create such communities because it can provide us with opportunities to teach our students that learning is a constant rehearsal. We must teach our students to do more than just choose the appropriate response. We must teach them to recognize what they know about their own learning and thinking, and we must provide them with opportunities to demonstrate what they know about reading and writing. We must give them the chance to demonstrate not only that they can read and write but that they understand what they are doing when they read and write

    Indiana Map Resources: Cadastral, Boundaries, PLSS Workgroup Projects

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    The IndianaMap.org website makes over 260 separate layers of GIS data and services easily discoverable, viewable, and available in various formats for use by everyone. This presentation will discuss how IndianaMap provides statewide GIS data layers and technology to help Indiana’s local, state, and federal governments and private entities to access authoritative statewide GIS map layers across Indiana; utilize statewide county parcel and address data with the newest orthophotography, LiDAR, and national hydrography data; support the desktop, web, and mobile mapping needs; provide national hydrological data (NHD—6 acre drainage maps for your area); access elevation data and show its potential uses (LiDAR—Open Topography site); utilize imagery from different time periods— what is available, how to access it, and the future needs for orthophotography; and provide county boundary status

    The perirhinal cortex and conceptual processing: Effects of feature-based statistics following damage to the anterior temporal lobes.

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    The anterior temporal lobe (ATL) plays a prominent role in models of semantic knowledge, although it remains unclear how the specific subregions within the ATL contribute to semantic memory. Patients with neurodegenerative diseases, like semantic dementia, have widespread damage to the ATL thus making inferences about the relationship between anatomy and cognition problematic. Here we take a detailed anatomical approach to ask which substructures within the ATL contribute to conceptual processing, with the prediction that the perirhinal cortex (PRc) will play a critical role for concepts that are more semantically confusable. We tested two patient groups, those with and without damage to the PRc, across two behavioural experiments - picture naming and word-picture matching. For both tasks, we manipulated the degree of semantic confusability of the concepts. By contrasting the performance of the two groups, along with healthy controls, we show that damage to the PRc results in worse performance in processing concepts with higher semantic confusability across both experiments. Further by correlating the degree of damage across anatomically defined regions of interest with performance, we find that PRc damage is related to performance for concepts with increased semantic confusability. Our results show that the PRc supports a necessary and crucial neurocognitve function that enables fine-grained conceptual processes to take place through the resolution of semantic confusability.This work was supported by funding from the European Research Council under the European Community's Seventh Framework Programme (FP7/2007-2013)/ERC Grant agreement no. 249640 to LKT.This is the final published version. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.neuropsychologia.2015.01.04

    What works in investigative interviewing? Using Systematic Maps to examine the evidence base

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    Competent investigative interviewing skills are key to securing reliable information from victims, witnesses, informants, and suspects. Information obtained in interviews often plays an important role in directing an investigation, informing effective decision-making, promoting efficient allocation of resources, as well as securing reliable prosecutions and mitigating risk of miscarriages of justice. However, effective investigative interviewing is a complex skill to master; demanding a sound understanding of the many cognitive, social, and environmental factors that influence the content and accuracy of witness and suspect accounts. To ensure that investigative interviewing and intelligence gathering produces usable, credible, and reliable information in an effective and ethically defensible manner, training and practice must be evidence-based. This short article outlines how practitioners, trainers and policy makers can navigate the best available research evidence to evaluate ‘what works?’ in investigative interviewing

    Age-related sensitivity to task-related modulation of language-processing networks.

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    It is widely assumed that cognitive functions decline with age and that these decrements are associated with age-related changes in patterns of functional activity. However, these functional changes may be due to age-related increased responsiveness to task demands and not to other cognitive processes on which neural and behavioural responses rely, since many ageing studies use task paradigms that may not be orthogonal to the cognitive function being investigated. Here we test this hypothesis in adults aged 20-86 years by combining measures of language comprehension, functional connectivity and neural integrity to identify functional networks activated in two language experiments with varying task demands. In one, participants listened to spoken sentences without performing an overt task (the natural listening condition) while in the other they performed a task in response to the same sentences. Using task-based ICA of fMRI, we identified a left-lateralised frontotemporal network associated with syntactic analysis, which remained consistently activated regardless of task demands. In contrast, in the task condition only a separate set of components showed task-specific activity in Opercular, Frontoparietal, and bilateral PFC. Only the PFC showed age-related increases in activation which, furthermore, was strongly mediated by grey matter health. These results suggest that, contrary to prevailing views, age-related changes in cognitive activation may be due in part to differential responses to task-related processes.RCUK, OtherThis is the final published version of the article "Age-related sensitivity to task-­related modulation of language-processing networks" published in Neuropsychologia here: http://www.sciencedirect.com/science/article/pii/S0028393214002802

    Identification of a variant in NDP associated with X-linked retinal dysplasia in the English cocker spaniel dog.

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    PURPOSE: Three related male English Cocker Spaniels (ECS) were reported to be congenitally blind. Examination of one of these revealed complete retinal detachment. A presumptive diagnosis of retinal dysplasia (RD) was provided and pedigree analysis was suggestive of an X-linked mode of inheritance. We sought to investigate the genetic basis of RD in this family of ECS. METHODS: Following whole genome sequencing (WGS) of the one remaining male RD-affected ECS, two distinct investigative approaches were employed: a candidate gene approach and a whole genome approach. In the candidate gene approach, COL9A2, COL9A3, NHEJ1, RS1 and NDP genes were investigated based on their known associations with RD and retinal detachment in dogs and humans. In the whole genome approach, affected WGS was compared with 814 unaffected canids to identify candidate variants, which were filtered based on appropriate segregation and predicted pathogenic effects followed by subsequent investigation of gene function. Candidate variants were tested for appropriate segregation in the ECS family and association with disease was assessed using samples from a total of 180 ECS. RESULTS: The same variant in NDP (c.653_654insC, p.Met114Hisfs*16) that was predicted to result in 15 aberrant amino acids before a premature stop in norrin protein, was identified independently by both approaches and was shown to segregate appropriately within the ECS family. Association of this variant with X-linked RD was significant (P = 0.0056). CONCLUSIONS: For the first time, we report a variant associated with canine X-linked RD. NDP variants are already known to cause X-linked RD, along with other abnormalities, in human Norrie disease. Thus, the dog may serve as a useful large animal model for research

    Reorganization of syntactic processing following left-hemisphere brain damage: does right-hemisphere activity preserve function?

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    The extent to which the human brain shows evidence of functional plasticity across the lifespan has been addressed in the context of pathological brain changes and, more recently, of the changes that take place during healthy ageing. Here we examine the potential for plasticity by asking whether a strongly left-lateralized system can successfully reorganize to the right-hemisphere following left-hemisphere brain damage. To do this, we focus on syntax, a key linguistic function considered to be strongly left-lateralized, combining measures of tissue integrity, neural activation and behavioural performance. In a functional neuroimaging study participants heard spoken sentences that differentially loaded on syntactic and semantic information. While healthy controls activated a left-hemisphere network of correlated activity including Brodmann areas 45/47 and posterior middle temporal gyrus during syntactic processing, patients activated Brodmann areas 45/47 bilaterally and right middle temporal gyrus. However, voxel-based morphometry analyses showed that only tissue integrity in left Brodmann areas 45/47 was correlated with activity and performance; poor tissue integrity in left Brodmann area 45 was associated with reduced functional activity and increased syntactic deficits. Activity in the right-hemisphere was not correlated with damage in the left-hemisphere or with performance. Reduced neural integrity in the left-hemisphere through brain damage or healthy ageing results in increased right-hemisphere activation in homologous regions to those left-hemisphere regions typically involved in the young. However, these regions do not support the same linguistic functions as those in the left-hemisphere and only indirectly contribute to preserved syntactic capacity. This establishes the unique role of the left hemisphere in syntax, a core component in human language
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