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The effect of variations in GRIN genes on the biogenesis and functional properties of the NMDA receptor
Kuchtiak, Viktor ; Balík, Aleš (advisor) ; Rozbeský, Daniel (referee) ; Ladislav, Marek (referee)
The expression and activity of ionotropic glutamate receptors control signal transduction at the excitatory synapses in the central nervous system. The major class are the calcium-permeable NMDA receptors that are fundamental for the various forms of synaptic plasticity, a key mechanism in the process of learning and memory formation. NMDA receptors are heterotetrameric and are represented by three types of subunits: GluN1, GluN2A-D, and GluN3A-B. Each subunit consists of four domains, with the intracellular C-terminal domain accounting for up to half of the entire NMDA receptor subunit (GluN2A/2B). A body of evidence indicates that the hypofunction of the NMDA receptor plays an important role in the pathogenesis of several neuropsychiatric disorders, including schizophrenia. Schizophrenia is characterised by a high degree of heritability, but its genetic background is not yet fully understood. Previous studies have identified in the human genome several individual loci that contribute to disease susceptibility, including the GRIN genes encoding NMDA receptors. Using a sequencing approach, we identified and annotated genetic variations across all GRIN genes in a cohort of schizophrenia patients and control subjects. The submitted doctoral thesis focuses on the functional analysis of the genetic...
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Microelectrode arrays for mioelectronic
Bráblíková, Aneta ; Vala, Martin (referee) ; Salyk, Ota (advisor)
Organic electronic biosensors are developed as suitable devices that can transform electrochemical processes within the cell membrane into an electronic signal and enable to measure electrical activity of excitable cells and tissues both in vitro and in vivo and thus represent valuable alternative to current cell monitoring methods. In this work we focus on the fabrication of electrophysiological sensors based on organic semiconductors printed by the material printing method. Microelectrode arrays (MEAs) are active components of the device, which can monitore cellular activity and above that stimulating cells with electrical pulses. The proposed platform should be used for cytotoxicity of potential drugs especially on cardiac cells (cardiomyocytes). The experimental part focus on specific production processes of platforms, which were prepared in the laboraty with emphasis on biocompatibility and conductivity of device.
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Optimalization of printing methods of organic semiconducting layers preparation
Ehlich, Jiří ; Vala, Martin (referee) ; Salyk, Ota (advisor)
Electrophysiological biosensors enables a novel way to measure electrical activity of biological structures both in-vitro and in-vivo and represents valuable alternative to current cellular activity measuring methods. Within this work we will be focusing on development of organic semiconductor (PEDOT:PSS) based Organic Electrochemical Transistors (OECTs) and optimization of material printing methods used in their development. These transistors are meant to be able to transfer electrochemical signals within the cell membrane to electrical signal. Such sensors should be used for cytotoxicity testing of chemicals and potential drugs on cardiomyocytes. Main benefits of OECTs are in their higher sensitivity thanks to their ability to locally amplify electric signals, better noise-signal ratio and outstanding biocompatibility. Their development is undemanding and inexpensive due material printing methods and materials processable at room temperatures.
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Time-frequency analysis of electrograms
Doležal, Petr ; Ronzhina, Marina (referee) ; Kolářová, Jana (advisor)
This thesis deals with time-frequency analysis of electrograms measured on isolated guinea pig hearts perfused according to Langendorff. Time-frequency analysis is based on algorithms Matching Pursuit and Wigner-Ville Distribution. The theoretical part describes the basics of electrocardiography, measurement on isolated hearts, the theory of approximation method Matching Pursuit and its combination with the Wigner-Ville distribution spectrum showing the energy density of the signal. Also other common approaches of time-frequency analysis are presented including the theory of continuous wavelet transform. The presented algorithms were tested on a set of electrograms, on which were induced ischemia within measurement followed by reperfusion. The proposed method allows for the fast detection of ischemia without any a priori knowledge of the signal, and also serves as a tool for measurement of EG important points and intervals. In the conclusion efficacy of the method was presented and its possible uses has been discussed.
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Electrostimulation method for cardiomyocyte life extension
Čermáková, Adéla ; Smital, Lukáš (referee) ; Čmiel, Vratislav (advisor)
This work deals with the electrophysiology of cardiac cells, their electro-stimulation and design of stimulation device to extend their life. The first part is focused on the action potential in general, in muscle cells, followed by an analysis of the process and characteristics of the action potential in cardiomyocytes. The next section provides a procedure for isolating and process of changes that lead to cell death and of a method that the process would be eliminated. Part of this work is a program for processing and evaluation of pictures obtained during electro-stimulation process.
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Expert System for Assessing the Type of Arrhythmia during Catheter Radiofrequency Ablation of Cardiac Arrhythmias
Šromová, Michaela ; Provazník, Ivo (referee) ; Sekora, Jiří (advisor)
The theoretical part of the thesis contains a brief description of the anatomy and electrophysiology of the heart, as well as both, surface and intracardiac electrocardiograms. The thesis also describes the different types of cardiac tachycardias, their differential diagnosis and what is known as The Expert System. The practical section of the thesis notes and outlines the tree diagrams, and additionally describes various software solutions of The Expert System. Further, the thesis includes the classification of the heart rhythm, using The Expert System method with three typical tachycardia cases, and including a list of questions asked by The Expert System to the user. Answers to all questions asked are being assessed in the text, as well as illustrated in submitted examples of intracardiac ECG recordings. The Expert System has been verified during a series of catheterization procedures on 26 patients (where the evaluated cardiac rhythm was 34). The classication of the type of heart rhythm (per The Expert System) when comparing the results with the doctors coincided in 100 % of tested cases.
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Electrostimulation method for cardiomyocyte life extension
Čermáková, Adéla ; Ronzhina, Marina (referee) ; Čmiel, Vratislav (advisor)
This work deals with electrostimulation cardiomyocytes and design stimulation device for their cultivation and stimulation. First part of work deals with electrophysiological myocytes and the next problems with electrostimulation and preserved their original morphology and physiology structure. The following section is designed and constructed stimulation device to improve cell viability. Stimulation took place under different conditions and the success rate depends on the number of cells that survived.
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Evaluation of heart arrhythmias
Šromová, Michaela ; Kozumplík, Jiří (referee) ; Provazník, Ivo (advisor)
The thesis is a brief description of the anatomy and electrophysiology of the heart. The thesis also describes the different types of electrocardiogram and cardiac arrhythmias with a description of their treatment. The next section provides design of a programme for the classification of selected types of arrhythmias, and three options for rhythm detection, using the length of RR intervals, finding extremes of P and R waves, measuring the length of intervals and heights of amplitudes. The practical part of this work was to create a rhythm classifier assigning appropriate treatment of arrhythmias, verification of its functions on the signals available from the library of arrhythmias and its evaluation.
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Extraction of spontaneously occurring activity patterns from an electrophysiological signal
Voldřich, Matěj ; Korvasová, Karolína (advisor) ; Riedlová, Kamila (referee)
To be able to elicit desired percepts using a cortical visual prosthesis, is it essential to understand the functional structure of the neural network under the implant. However, in a blind individual the functional proper- ties of neurons cannot be measured by recording responses to visual stimuli and information can only be extracted from spontaneous activity. Spon- taneous activity in the primary visual cortex (V1) of anesthetized primates has been shown to encode information about local functional architecture of the neural network. Particularly, inference of the orientation-preference map from spontaneous activity has been achieved in non-human animals using in- vasive imaging techniques that are not intended for applications in humans. Whether the same inference is possible with spatially sparse electrophysiolo- gical recordings from a micro-electrode array that is currently used as a cortical visual prosthesis remains unknown. The aim of this thesis is to use automatic spatial pattern detection algorithm for orientation preference map inference from spontaneous activity and compare outcomes using four differ- ent variables extracted from signal recorded with intracranial micro-electrode arrays in awake macaque monkeys. 1
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Functional and pharmacological properties of GluN1/GluN2 and GluN1/GluN3 subtypes of NMDA receptors
Kolcheva, Marharyta ; Horák, Martin (advisor) ; Bohačiaková, Dáša (referee) ; Balaštík, Martin (referee)
(EN) N-methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors and they play a critical role in excitatory synaptic transmission in the mammalian central nervous system (CNS). Hyperactivity or hypoactivity of NMDARs can lead to a wide spectrum of pathological conditions and psychiatric disorders, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, epilepsy, schizophrenia. NMDARs form a heterotetrameric complex made up of GluN1, GluN2(A-D) and/or GluN3(A, B) subunits. Different subtypes of NMDARs could have various effects on disease pathogenesis and therefore it is crucial to investigate the specific role of each subunit in the regulation of normal NMDAR functioning. The regulation of NMDARs occurs at different levels, from early processing, including synthesis, assembly, quality control in the endoplasmic reticulum (ER), trafficking to the cell surface, to internalization, recycling, and degradation. In this dissertation, we mainly focused on determining the roles of extracellular and transmembrane regions of different subtypes of NMDARs in the regulation of their function. In particular, using electrophysiology and microscopy methods on HEK293 cells and cultured hippocampal neurons, we investigated: (i) the impact of N-glycosylation and different lectins on...
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