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Study of metabolic syndrome in mice model: roles of dietary lipids, adipose tissue and AMP-activated protein kinase
Medříková, Daša ; Kopecký, Jan (advisor) ; Houštěk, Josef (referee) ; Novotný, Jiří (referee)
Obesity and associated metabolic disorders, e. g. metabolic syndrome, represent a considerable health threat for modern society. Due to sedentary lifestyle, high caloric intake and changes in composition of diet, prevalence of obesity is increasing worldwide. One of the possible causes contributing to higher prevalence of obesity in recent population could be the change of fatty acids (FA) composition of dietary lipids, with the shift in the content of n-6 and n-3 FA toward n-6 FA. In contrast to n-6 FA, n-3 FA are known for their anti-atherogenic, anti-obesogenic and anti-inflammatory properties. In our experiments in mice, the capability of naturally occurred and chemically modified n- 3 long chain polyunsaturated fatty acids (LC-PUFA) in prevention and reversal of specific parts of metabolic syndrome was demonstrated. A specific chemical derivative of docosahexaenoic acid was proven to be very effective in preventing and improving metabolic conditions of animals exposed to high-fat (HF) diet challenge. Further, the involvement of AMP-activated protein kinase (AMPK), a master regulator of lipid metabolism, in skeletal muscle thermogenesis induced by HF-feeding was investigated. Activation of AMPK in the HF-fed mice is most possibly caused by increased leptin levels and represents an important link...
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Scattering of the electroweak vector bosons
Morávek, Petr ; Hořejší, Jiří (advisor) ; Novotný, Jiří (referee)
In the present work we study the scattering of vector gauge bosons in the framework of higher dimensional theory of Kaluza-Klein type. This work provides an instructive introduction to the given problematics with all technical details of the relevant calculations. The basic ideas of the theory are demonstrated on a set of simple models. Particular attention is paid to the selection of consistent boundary conditions using the variational principle of least action, gauge invariance and tree-level unitarity of longitudinal gauge bosons scattering.
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The role of TRPV1 receptors in nociceptive signalling at spinal cord level
Mrózková, Petra ; Paleček, Jiří (advisor) ; Novotný, Jiří (referee) ; Krůšek, Jan (referee)
Modulation of nociceptive synaptic transmission in the spinal cord dorsal horn plays a key role in the development and maintenance of pathological pain states and chronic pain diseases. Important role in this process play Transient receptor potential Vanilloid 1 receptors (TRPV1), present on presynaptic endings of primary afferents in the superficial spinal cord dorsal horn. Changes in TRPV1 activity have significant impact on nociceptive transmission. There are number of processes that influence the function of spinal TRPV1 receptors. This work is focused on the role of protease-activated receptors type 2 (PAR2), C-C motif chemokine ligand 2 (CCL2) and the effect of chemotherapeutic drug paclitaxel in modulation of synaptic nociceptive transmission and activation of TRPV1 receptors. PAR2 receptors belong to a family of four G-protein-coupled receptors activated by proteases. The role of PAR2 receptors in pain perception is closely related to their presence in a population of dorsal root ganglion neurons, where they are also co-expressed with TRPV1. Activation of PAR2 may lead to peripheral and central sensitization. Chemokine CCL2 and its main receptor CCR2 were suggested to be an important factor in the development of neuropathic pain after peripheral nerve injury. In our study we focused on the...
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Dimensional transmutation in quantum theory
Ebr, Jan ; Hořejší, Jiří (advisor) ; Novotný, Jiří (referee)
This work deals with two models - from the quantum eld theory it is the massless scalar electrodynamics (the so-called Coleman-Weinberg model) and from quantum mechanics it is the contact (-function) potential (in two dimensions) - that are apparently invariant under some sort of scale transformations and thus they, in suitably chosen units, contain only dimensionless parameters. It turns out that even in the quantum-mechanical case one has to add an additional procedure to the formal denition of the model and that the use of dierent physical regulators leads to the same results, that furthermore agree with the predictions of the mathematically rigorous method of self-adjoint operator extensions. In this work, we present detailed calculations supporting this result. Contrary to the common literature, we do so in a straightforward manner, which can be followed step by step (with all the necessary elements of functional analysis summarised in the Appendix). In quantum eld theory we apply a similar approach, when we "rediscover" the results of the abstract functional methods in the ordinary perturbation theory. In its framework, we further show how to obtain predictions also for other quantities than particle masses.
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Regulation of promyelocytic leukemia protein expression
Dobrovolná, Jana ; Hodný, Zdeněk (advisor) ; Novotný, Jiří (referee) ; Kovarik, Pavel (referee)
4. CONCLUSIONS Major resultsof this PhD thesiscanbe summarizedas follows: |. For full tÍanscTiptionalactivationof ISG @ML' Sp100'IRFI) by inteďeronor'the deaceýlationof unknownfactor(s)is necessary.IFNer.inducedexpressionof PML at mRNA andproteinlevel and zubsequentincreaseof PML NBs are suppressedby all tested HDACIs independentlyon cellular origin. Importantly,baml (i.e. IFNc- nonstimulated)expressionof PML is not influencedby ÍIDACIs. The classical Jak. STAT pathwaymediatingtransitionof IFNo signalremainsunaffectedby HDACIs and the targetof HDACIs lies downstreamof ISGF3 binding to PML promoter. AdverseaffectsofHDACIs usedin clinical praxisarepredicted. 2. Human mesenchymalstem cells (gfowing, confluent or terminally differentiated) expressPML protein,form PML nuclearboďes and respondto IFNcr teaEnent by dramaticelevationof PML mRNA andproteinlevels and mďerate increaseof PML NBs. Numberof PML NBs per cell nucleusis depende,nton thecultureproliferative age. ln normal diploid but not in immorbl cells PML forms various nucleoli- associatedshuctuÍes.The localization of PML into nucleoli is teestablishedin senescentcells. The importanc€ of PML association with nucleoli for its fumor suppressoractivitiesis hypothesized. 3. Drug-induced senescencein several human cell lines leads to increased PML...
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