14 research outputs found

    Multimodal Investigation of Neuronal Responses

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    This thesis describes an investigation of neuronal responses with both magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). MEG and fMRI are widely used in neuroscience. However, aspects of the MEG and fMRI signal are still not well understood, particularly post-stimulus responses – responses which occur after a stimulus has ended. Post-stimulus responses have been shown to correlate with various illnesses and as a result, MEG and fMRI have yet to reach their full potential clinically. By developing carefully controlled experiments, MEG is used in this thesis to characterise post-stimulus responses to a grip-force task. The results showed that the beta-band post-stimulus response (post-movement beta rebound, PMBR) is modulated by task duration. Functional network analysis, using amplitude envelope correlation and a hidden Markov model, showed that the PMBR re-establishes networks after breaking down during a task, suggesting the PMBR is related to functional connectivity. The results of this thesis provide new information about the nature of the PMBR, demonstrating that it can be systematically controlled by task parameters and provides insight into its generation. It is hoped this research will contribute to a deeper understanding of the PMBR and provide a step forward for its use clinically. In fMRI, the origin of the post-stimulus response is also poorly understood. To investigate fMRI post-stimulus responses, an MR pulse sequence was developed and optimised to measure blood flow, volume and oxygenation changes simultaneously at 7 T. This was implemented with the grip-force task, allowing direct comparison between MEG and fMRI. This study provides new insights into the fMRI post-stimulus undershoot which warrant further investigation. Understanding the link between fMRI and MEG signals will help further understanding of both modalities and how they relate to neuronal activity. Finally, the applications of fMRI were explored by comparing fMRI responses in patients with focal hand dystonia (FHD) with healthy controls. 7 T fMRI was used to map cortical fingertip representations and measures were developed to compare overlap of digit representations between patients and healthy controls. This project provided an important opportunity to advance the understanding of FHD and was the first study to use fMRI to explore the effects of treatment on patients with FHD

    60th Annual Rocky Mountain Conference on Magnetic Resonance

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    Final program, abstracts, and information about the 60th annual meeting of the Rocky Mountain Conference on Magnetic Resonance, co-endorsed by the Colorado Section of the American Chemical Society and the Society for Applied Spectroscopy. Held in Denver, Colorado, July 21-25, 2019

    Extracellular vesicles from induced neurons trigger epigenetic silencing of a brain neurotransmitter.

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    Introduction: Antithrombin (AT) is a glycoprotein involved in the regulation of blood coagulation. It belongs to the family of serine-protease inhibitors and acts as the most important antagonist of different clot- ting factors. Two types of inherited AT deficiency can be distinguished: Type I (quantitative deficit), and Type II (qualitative deficit). The latter is characterized by an impaired inhibitory activity related to dysfunc- tional domains of the protein. Three Type II subtypes can be defined: Type IIa (reactive site defect), Type IIb (heparin binding site defect) and Type IIc (pleiotropic defect). This classification has clinical importance since these subtypes have a different thrombotic risk. No functional routine diagnostic assay, however, can be assumed to detect all forms of Type II deficiencies since false-negative results may hamper the diagnosis. Methods: We analysed the biochemical/biophysical association of ATT to EVs. We separated EVs from plasma of healthy or Type II affected patients or from cultured hepatocytes through differential ultracentrifu- gation followed by sucrose density gradient and/or immunoprecipitation. We next combined dot blot ana- lysis, WB, 2D electrophoresis and enzymatic assays to reveal the nature of ATT association to EVs. Results: We evidenced that ATT is associated to the external leaflet of EVs. We also found that specific ATT isoforms are enriched in EV preparations in respect to total plasma and that those isoforms are selectively associated to EVs when comparing healthy or ATT type II deficient patients. Summary/Conclusion: ATT selective association pat- tern to EVs might be related either to mutations in the primary sequence of the protein or alterations in the glycosylation process, hence experiments are ongoing to reveal the nature of this phenomenon. Our findings suggest that analysis of ATT enriched in EV prepara- tions might be useful to gain insights into the patho- genesis and be of support in the diagnostic algorithm of ATT deficiency. Funding: This work acknowledges FFABR (Fondo finanziamento attivitĂ  Base di ricerca from MIUR, Ministry of Education, Universities and Research, Italy) for financial support

    Library websites popularity: does Facebook really matter?

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    The purpose of this paper is to determine whether the utilization of social media (Facebook) is an important factor in increasing the visibility of the library site usage in Malaysian public universities. Nine top ranked Malaysian public universities involved in this research and number of Facebook followers for each library website is listed. Alexa software was used as the approach to study the issue of visibility. Alexa is able to determine web site usage, by showing the percentage of visitors of library related subdomain(s) as listed in the top subdomains for each University website (domain) over a month. It is found that Universiti Utara Malaysia library website scored the highest percentage of visitors based on the library related subdomain(s) as listed in the top subdomains for the University website in Alexa. To check such irregularities in access, this paper use EvalAccess 2.0 and it is found that Universiti Sains Malaysia’s library website scored higher irregularities. In term of number of Facebook followers, Univesity of Malaya library has the highest score. It is showed that the utilization of social media (Facebook) is not yet an important factor in increasing the visibility of the library websites. However, expectedly, top ranked universities’ library web sites, are more visible and popular. This research is limited to the situation in Malaysia where public universities are more noticeable and seldom face financial constraints rather than private universities. It is highly important for those universities’ library web sites that are not highly visible to initiate the necessary measures in improving the development of their web sites as the usage of the website is an indicator of online quality

    Single molecule studies on actin folding by the eukaryotic chaperonin CCT

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    The eukaryotic, cytosolic chaperonin containing TCP-1 (CCT) is a protein folding nanomachine. CCT is a 1 MDa double-ring-structured ATPase which assists nascent polypeptides to reach their native conformational state. Obligate substrates include the cytoskeletal components actin and tubulin. Whilst significant structural studies have been conducted, relatively little is known about the dynamics of the ATP-dependent folding process. Total Internal Reflection Fluorescence (TIRF) microscopy is a high signal to noise, single molecule, microscopy technique which has been previously used to observe both protein dynamics and extract enzyme kinetics at the single molecule level. We have immobilised functional CCT onto silica surfaces in order to extract dwell times and kinetics of the folding process, as CCT captures, folds and releases actin from its unfolded state to the folded G-actin monomer. A method for the immobilisation of CCT, via a calmodulin protein, has been developed. Mutant CCT-6CBP has a calmodulin binding peptide tag inserted into the apical domain of the CCT6 subunit and can be affinity captured via calmodulin immobilised to a borosilicate surface. The calmodulin-CCT interaction is calcium dependent and can be reversed allowing for discrimination between specific versus non-specific binding. ATP-dependent release of unfolded actin from CCT complexes immobilised to silica surfaces has proven to be problematic. Complexes can be specifically bound but subsequently seem to lose functional folding behaviour. Attempts to count the numbers of the stimulatory cofactor phosducin-like protein 2 (PLP2) and actin monomers bound to the CCT complex, utilising photobleaching, is described. A program for the analysis of single molecule traces was written. Incorporating a Chung-Kennedy non-linear filter, this program provides stoichiometric data consistent with spectrophotometric methods. Analysis of CCT-actin-PLP2 complexes was not possible due to time constraints.Open Acces

    The integration of bottom-up and top-down signals in human perception in health and disease

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    To extract a meaningful visual experience from the information falling on the retina, the visual system must integrate signals from multiple levels. Bottom-up signals provide input relating to local features while top-down signals provide contextual feedback and reflect internal states of the organism. In this thesis I will explore the nature and neural basis of this integration in two key areas. I will examine perceptual filling-in of artificial scotomas to investigate the bottom-up signals causing changes in perception when filling-in takes place. I will then examine how this perceptual filling-in is modified by top-down signals reflecting attention and working memory. I will also investigate hemianopic completion, an unusual form of filling-in, which may reflect a breakdown in top-down feedback from higher visual areas. The second part of the thesis will explore a different form of top-down control of visual processing. While the effects of cognitive mechanisms such as attention on visual processing are well-characterised, other types of top-down signal such as reward outcome are less well explored. I will therefore study whether signals relating to reward can influence visual processing. To address these questions, I will employ a range of methodologies including functional MRI, magnetoencephalography and behavioural testing in healthy participants and patients with cortical damage. I will demonstrate that perceptual filling-in of artificial scotomas is largely a bottom-up process but that higher cognitive functions can modulate the phenomenon. I will also show that reward modulates activity in higher visual areas in the absence of concurrent visual stimulation and that receiving reward leads to enhanced activity in primary visual cortex on the next trial. These findings reveal that integration occurs across multiple levels even for processes rooted in early retinotopic regions, and that higher cognitive processes such as reward can influence the earliest stages of cortical visual processing

    Queensland University of Technology: Handbook 1993

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    The Queensland University of Technology handbook gives an outline of the faculties and subject offerings available that were offered by QUT

    Queensland University of Technology: Handbook 1992

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    The Queensland University of Technology handbook gives an outline of the faculties and subject offerings available that were offered by QUT
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