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The effect of 14-3-3 protein on intradomain interaction of ubiquitin ligase Nedd4-2
Pohl, Pavel ; Obšilová, Veronika (advisor) ; Žáková, Lenka (referee) ; Pavlíček, Jiří (referee)
EN The human ubiquitin ligase Nedd4-2 (NEDD4L) ubiquitinates a wide range of membrane proteins and receptors, playing a key role in maintaining homeostasis. This enzyme is regulated by phosphorylation and subsequent interaction with 14-3-3 proteins, which primarily affects its ability to interact with various substrates. However, very little is known about the molecular basis of this protein-protein interaction. In this work, we focused on biophysical characterization of the role of individual phosphorylation sites and also on mapping the structural changes in the Nedd4- 2 protein induced by 14-3-3 protein binding. Our experiments using analytical ultracentrifugation methods revealed that two phosphorylation sites Ser342 and Ser448 are primarily required for stable binding of Nedd4-2 to 14-3-3 proteins. The crystal structure of the 14-3-3ηΔC:Nedd4-2335-455 T367A complex than revealed the simultaneous binding of both phosphorylated residues to the binding groove of 14-3-3 protein. Subsequent modeling based on small-angle X-ray scattering and chemical cross-linking data combined with mass spectrometry indicated extensive structural changes in the individual domains of the Nedd4-2 protein. Binding of 14-3-3η protein blocks the WW3 domain of Nedd4-2 in the central channel of 14-3-3 protein, while...
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The preparation and characterization of IGF2 prohormones
Potalitsyn, Pavlo ; Žáková, Lenka (advisor) ; Obšilová, Veronika (referee) ; Hudeček, Jiří (referee)
Insulin-like growth factors 1 and 2 are protein hormones that share similar structural and functional features with insulin. They are commonly abbreviated as IGF1 and IGF2. They play important roles in prenatal development and throughout lifespan. Stimulation of growth of all cell types and significant metabolic effects also belong among their known functions. Dysregulation of their activity or elevated levels were observed in a number of diseases such as diabetes mellitus type 2, cancer, hyperthyroidism, amyotrophic lateral sclerosis, muscle dystrophy, acromegaly, Laron dwarfism and other disorders. Functions of IGF2 are less studied than functions of the other members of the family and even less is known about precursors of IGF2. To address these issues we started with production of IGF2 analogues with enhanced specificity to IR for better understanding the mechanism of receptor activation by IGF2. We produced site-specific analogues modified at sites important for receptor binding. IGF2 analogue with Phe48His mutation is the strongest IGF2-derived binder for IR-A reported ever and it is able to activate IR-A to about 60% of insulin ability. We developed new rapid, robust, and sensitive binding assays for testing of ligands of the receptor for IGF2 (IGF2R). First, we immobilized domain 11 of...
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Physiotherapeutic approaches in the treatment of patellofemoral pain syndrome - a systematic review
Řehořová, Veronika ; Pavlů, Dagmar (advisor) ; Žáková, Lenka (referee)
Title: Physiotherapeutic Approaches in the Treatment of Patellofemoral Pain Syndrome - a Systematic Review Objectives: The objective of this diploma thesis is to evaluate physiotherapeutic procedures currently used in the conservative treatment of patellofemoral pain syndrome and to determine the most effective procedure in reducing pain. Other objectives include a summarisation of the issue of patellofemoral pain syndrome from the perspective of etiology and epidemiology, clinical picture, diagnosis and the possibilities of various therapeutic procedures. Methods: The diploma thesis uses systematic literature review and is analytical-descriptive in nature. The methodology chapter sets out tasks, the thesis process and individual research criteria according to which the thesis was written. Results: Following the research, 10 studies were included in the evaluation based on the established criteria. The results show that the following physiotherapeutic interventions are currently used in the conservative treatment of patellofemoral pain syndrome: an exercise programme aimed at strengthening the muscles of the hip and knee joint alone or in combination with kinesio taping, mobilisation with movement, full-body vibration training, resistance and proprioceptive exercises, functional training aimed at...
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Anterior cruciate ligament rupture in women floorball extraleague players in Czech and Slovak republic - analysis of influences
Boľová, Šárka ; Pavlů, Dagmar (advisor) ; Žáková, Lenka (referee)
Title: Anterior cruciate ligament rupture in women floorball extraleague players in Czech and Slovak republic - analysis of influences Objectives: The aim of the diploma thesis is to analyze the main influences on the anterior cruciate ligament rupture in top-level women floorball players in the Czech and Slovak top leagues, with the main focus on the length of player's active career and average week load, including a comparison of incidences of the injury in both countries. Methods: Data collection was done using an anonymous non-standardized questionnaire in electronic form. The research group included 209 top women floorball players aged 15-35 years. 135 players played in the Czech extraleague and 74 in the Slovak extraleague. All 20 teams registered in the highest women's floorball competitions of both countries during season 2021/2022 took part in the research. Results: The results showed a predominance of non-contact injuries (75 %), repeated anterior cruciate ligament rupture occurred in 42.5 % of cases. The effect of the player's active career length (long-term repetitive tissue microtrauma) on the injury was confirmed. The relationship between the volume of the average week training and match load (short-term loading) and the injury was not confirmed. There was a significant difference in...
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Frozen shoulder sy - effective physiotherapeutic approaches: systematic review
Drhlík, Michal ; Pavlů, Dagmar (advisor) ; Žáková, Lenka (referee)
Title: Frozen shoulder syndrome - effective physiotherapeutic approaches: systematic review Objectives: The aim of this work was to determine from studies concerning the treatment of the primary form of frozen shoulder syndrome using physiotherapeutic methods and published in the last 10 years, which brings the best results in reducing pain, increasing range of motion and improving affected shoulder function. Methods: Randomized controlled studies (double and single-blind) dealing with the physiotherapeutic intervention of frozen shoulder treatment with a data range of publications from September 1, 2011 to August 31, 2021 were searched. 3 databases were selected for this purpose: Cochrane Library, PubMed and Web of Science. Articles could be written in English, Czech, German, Slovak or Spanish. Different names of the studied disease were chosen as key words: adhesive capsulitis, contracted shoulder, frozen shoulder and periarthritis. Only articles with most probands between the ages of 30 and 70 were included. Persons with associated shoulder joint diseases such as rheumatoid arthritis (excluding diabetes mellitus) were excluded. The analysis of selected articles was performed from clearly compiled tables for individual studies and from 3 summary tables of associated individual physiotherapeutic...
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Case study of physiotherapeutic care of a patient with the diagnosis total hip replacement
Smažíková, Jana ; Žáková, Lenka (advisor) ; Vrbický, David (referee)
Title: The case study of physiotherapy treatment of a patient with the diagnosis of total hip endoprothesis replacement Objectives: The aim of this bachelor's thesis is to summarize theoretical knowledge of the total hip endoprothesis replacement diagnosis in the first part. The second part is focused on elaboration of the case study of a patient with this diagnosis. Methods:This bachelor's thesis was completed on the basis of internship on the rehabilitation and physical medicine ward of the Ústřední vojenská nemocnice in Prague between 10. 1. 2022 - 4. 2. 2022. This bachelor's thesis is divided into two sections. The first section, general, resumes the diagnosis of total hip endoprothesis replacement information drawn from scientific literature. The second section, special, includes a case study of a patient with this diagnosis. It contains initial kinesiological analysis, the aim of therapy, suggestion and description of given therapy, it's effect and final kinesiological analysis. Results: In the general section of the thesis, I was able to summarize theoretical information about the diagnosis of total hip ensoprothesis replacement. In the special section, I processed a complete case study of a patient with this diagnosis. During the therapies, the health state of the patient increased...
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Physical activity and sports history of children 11 to 19 years old
Babický, Lukáš ; Nováková, Tereza (advisor) ; Žáková, Lenka (referee)
Title: Physical activity and sports history of children 11 to 19 years old Objectives: To analyse the level of leisure physical activity and its specifics on a sample of the adolescent population. To analyse the activity development from the historical perspective of the proband from the initial experience with organized physical activity. The results of the survey are further compared with the conclusions of previous studies on the issue. Methods: A total of 563 respondents (235 boys and 328 girls) from Prague's Gymnasiums (secondary grammar schools) took part in the research. Data were obtained using a questionnaire survey (CAWI) based on preliminary research and evaluated using MS Excel, GraphPad Prism and mathematical software R. Results: The preference of single sport (63.8 %) was found in the examined population with a predominance of the frequency of 2 to 4 trainings per week (61.2 %). The vast majority (93.6 %) stated that they were participated fundamental movement training at a younger school age. More than half (61 %) experienced pain or injury within physical activity, especially in the lower limbs (61.9 %). Less than half of respondents (46.3 %) have already visited a physiotherapist. The main factor in the cessation of physical activity is psychosocial reasons (76.9 %). Increasing age...
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Synthesis of Trichloroacetyl Esters of Aldols
Žáková, Lenka ; Kubíček, Vladimír (advisor) ; Jezberová, Michaela (referee)
This diploma thesis describes synthesis of trichloroacetyl esters of aldols which were obtained by a reaction of trichloroacetic acid with formaldehyde and another comercial aldehyde. Used were hydratopaldehyde, isobutyraldehyde, 2-methylpentanal, 2-ethylhexanal and 2-ethylbutanal. Some of these esters were described in the literature but only in part, several of them are new compounds. Excellent yields and clean products prove that the applied method is a good way to achieve these compounds that can be easily used for further processes.
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Study of the role of the B-chain N-terminus conformation of insulin in binding to the insulin receptor
Kosinová, Lucie ; Žáková, Lenka (advisor) ; Obšil, Tomáš (referee)
According to the International Diabetes Federation (IDF), there were 371 million people in the age from 20 to 79 years worldwide affected by diabetes in 2012. This means diabetes has become a global epidemic disease and, therefore, the importace of insulin research still grows. Insulin is a protein hormone that plays a key role in regulating blood glucose level which has a widespread impact on whole metabolism. Insulin acts through binding of its monomeric form to the insulin receptor. It is clear that insulin monomer has to undergo structural changes upon binding to the insulin receptor as the residues which are crucial for the interaction are burried within the native form. According to studies of highly active hormone analogs and the new information about the insulin-insulin receptor complex, there is a strong evidence that the C-terminal part of the B-chain is a dynamic element in insulin activation and receptor binding. Probably, there is also a great importance of the B-chain N- terminus and the transition between T and R conformations of insulin. However, the exact significance of the T and R states of insulin still remains unclear. In this work, several new insulin analogs AibB3-insulin, AibB5-insulin, AibB8- insulin, N-MeAlaB8-insulin and D-ProB8-insulin were prepared for the purpose of...
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Evaluation of the strength of selected muscle groups and the range of motion in sport aerobics athletes
Sílová, Markéta ; Žáková, Lenka (advisor) ; Vomáčková, Helena (referee)
Title: Evaluation of the strength of selected muscle groups and the range of motion in sport aerobics athletes Objective: Sport aerobics belongs to group of sport gymnastics, which brings increased demands especially on joint mobility, muscle strength and coordination of movement. Athletes are selected according to these prerequisites the development of which is still supported by training. The thesis follow up the physical measurement of these attributes. The Aim: Evaluation of joint mobility and muscle strength of 12-16 year old sport aerobic athletes and their correlations. Furthermore, the comparison together with the level of the performance group. Method: Measurement of joint mobility using goniometry, hypermobility evaluation using Beighton score, measurement of the muscle strength using HUMAC isokinetic dynamometer. Comparison of measured results with performance group level. Results: During measurement of the joint range using the method goniometry was found, that in flexion of the hip joint had 100 % of the athletes increased joint motion. In hip extension, the joint range wasn't increased at all. Beighton score showed, that 90 % of athletes were constitutionally hypermobile. The relationship between joint range and the values of the muscle strength - peak torque has not been proven. Key...
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