Role genu Nkx2.5 v morfogenezi a elektrofyziologii srdce u myši

Role genu Nkx2.5 v morfogenezi a elektrofyziologii srdce u myši Praha 2016 Bc. Peter Hámor ABSTRAKT Cieľom tejto práce je skúmanie vplyvu dávkovania génu Nkx2.5 na elektrofyziológiu srdca myší v prenatálnom období vývoja. Hlavnou úlohou je hľadanie rozdielov vo vedení elektrického vzruchu v srdci myších embryí v závislosti na ich genotype. Bola na to použitá špecifická metóda snímania prechodu elektrického vzruchu myokardom, tzv. optické mapovanie. Vďaka tejto metóde bolo možné vytvoriť obrázky a videá zachytávajúce prechod elektrického impulzu srdcom, s označením začiatku a smerovania jeho vedenia. Z výstupov týchto snímaní, tzv. optických máp, sú určené prípadné anomálie a výchylky v porovnaní s normálnou funkciou srdca. Práca sa zameriava na expresiu transkripčného faktoru Nkx2.5 a s ním súvisiacich regulačných prvkov, ktoré sa podieľajú na správnom formovaní a fyziológii srdca do obdobia vývoja približne 9,5 dní post coitum (d.p.c.). Jedinci v tomto vývojovom štádiu boli opticky mapovaní a porovnávaní na základe ich genotypu - homozygotne nemutantné, heterozygotné a homozygotne mutantné myšie embryá vykazovali určité podobné vlastnosti, kým v niektorých sa dramaticky líšili. Keďže táto práca je jedna z mála, ktorá detailne skúma optické mapy homozygotne mutantných jedincov v géne Nkx2.5, výsledky z nej...Role of Nkx2.5 in development and electrophysiology of the mouse heart Prague 2016 Peter Hámor, B.S. ABSTRACT The objective of this thesis is to investigate the role of Nkx2.5 gene dosage on electrophysiology of the mouse heart in prenatal stage of its development. The main goal of this work is to search for differences in conduction of electric impulses through the embryonic mouse hearts of different genotype. Special method of capturing the conduction of electric impulse through myocardium, called optical mapping, was used to visualize the electrical activity. Thanks to this method I was able to construct images and videos capturing the spread of the impulse with identification of the beginning of the activation and its direction in the heart. These outputs, or optical maps, help to define anomalies and defects in mutants compared with a normal functioning heart. The thesis focuses on the expression of the transcription factor Nkx2.5 and regulatory components related with the correct formation and physiology of the heart until 9.5 days post coitum. Embryos at this developmental stage were optically mapped and analysed according to their genotype. While the wild type and heterozygote mouse embryos exhibited high degree of similarity, the homozygous mutants were dramatically different. Considering this work...Department of Cell BiologyKatedra buněčné biologiePřírodovědecká fakultaFaculty of Scienc

A szolidaritás világától a szép új világig?

Mi az oka annak, hogy mindenütt válságban van az egészségügy rendszere, és mindenütt keresik a megoldás lehetőségét? Fenntarthatóak-e az elmúlt évtizedek társadalmi, technikai, gazdasági változásai nyomán a szolidaritáson és a generációk közötti társadalmi szerződésen alapuló jóléti rendszerek? Reform, gyökeres megújulás vagy elegendő a meglévő rendszer finomszabályozása, erre keresi a választ a cikk szerzője, a különböző elven működtetett egészségügyi rendszerek mechanizmusainak, finanszírozási módjainak áttekintésével

Vliv dávkování genu Nkx2.5 na vývoj a elektrofyziologii srdce u myši

Vliv dávkování genu Nkx2.5 na vývoj a elektrofyziologii srdce u myši Praha 2015 Bc. Peter Hámor ABSTRAKT Cieľom tejto práce je skúmanie vplyvu dávkovania génu Nkx2.5 na elektrofyziológiu srdca myší v prenatálnom období vývoja, v ktorom dochádza ku skolabovaniu jeho fyziologických funkcií. Hlavnou úlohou je hľadanie rozdielov vo vedení elektrického vzruchu v srdci myších embryí v závislosti na ich genotype. Bola na to použitá špecifická metóda snímania prechodu elektrického vzruchu myokardom, tzv. optické mapovanie. Vďaka tejto metóde bolo možné vytvoriť obrázky a videá zachytávajúce prechod elektrického impulzu srdcom, s označením začiatku a smerovania jeho vedenia. Z výstupov týchto snímaní, optických máp, sú určené prípadné anomálie a výchylky v porovnaní s normálnou funkciou srdca. Práca sa zameriava na expresiu transkripčného faktoru Nkx2.5 a s ním súvisiacich regulačných prvkov, ktoré sa podieľajú na správnom formovaní a fyziológii srdca do obdobia vývoja približne 9,5 dní post coitum (d.p.c). Jedinci v tomto vývojovom štádiu boli opticky mapovaní a porovnávaní na základe ich genotypu - homozygotne nemutantné, heterozygotné a homozygotne mutantné myšie embryá vykazovali určité podobné vlastnosti, kým v niektorých sa dramaticky líšili. Keďže táto práca je jedna z mála, ktorá detailne skúma optické mapy...Role of Nkx2.5 on development and electrophysiology of the mouse heart Prague 2015 Bc. Peter Hámor ABSTRACT The objective of this thesis is to investigate the role of Nkx2.5 gene dosage on electrophysiology of the mouse heart in prenatal stage of its development, in which the physiological functions of the heart fail to function properly. The main goal of this work is to search for differences in conduction of electric impulses through the embryonic mouse heart according to their genotype. Special method of capturing the conduction of electric impulse through myocardium was used for this purpose, called optical mapping. Thanks to this method I was able to construct images and videos capturing transition of the impulse with marked beginning of the activation and its direction in the heart. These outputs, or optical maps, help to define anomalies and defects compared with a normal functioning heart. The thesis focuses on the expression of the transcription factor Nkx2.5 and regulatory components related with the correct formation and physiology of the heart until 9.5 days post coitum. Individuals in this developmental stage were optically mapped and compared according to their genotypes - homozygous non-mutant, heterozygote and homozygous mutant mouse embryos exhibited some degree of similarity, while other...Department of Cell BiologyKatedra buněčné biologiePřírodovědecká fakultaFaculty of Scienc

Cílená diferenciace mezenchymálních kmenových buněk a jejich využití v klinické praxi

Cílem této práce je úvod do možností neurální diferenciace mezenchymálních kmenových buněk a jejich využití v klinické praxi zaměřené na opravu a regeneraci tkání centrální nervové soustavy. Protože tato soustava představuje řídící centrum funkčních vlastností celého těla a léčba zranění a degenerací často přináší mnoho problémů a překážek, je možnost využití vlastních buněk jako transplantátu nebo podpory přirozených regeneračních vlastností tkání hodna hlubšího zkoumání. Práce se postupně zaměřuje na obecné vlastnosti a charakteristiku kmenových buněk a jejich diferenciačního potenciálu, následně jsou podrobněji charakterizované mezenchymální kmenové buňky společně s možností jejich izolace a kultivace. Hlavní část textu tvoří rešerše studií a metod zaměřených na cílenou diferenciaci mezenchymálních kmenový buněk se snahou o jejich transdiferenciaci do buněk neurální buněčné linie, společně se současným a předpokládaným využitím těchto buněk v terapiích centrální nervové soustavy.The goal of this work is to point out possibilities of neuronal differentiation of mesenchymal stem cells and their application for clinical purposes, primary for repairing and regeneration of central nervous system tissues. Because this system works as a control center for functional features of the whole body, and treating this injuries and degenerations often bring many problems and obstacles, the possibility of using autologous cells for a transplantation or inducer of the natural regenerative properties of tissues is worth deeper research. This work progressively focuses on basic characteristics of stem cells and their differentiation potential, characterizing further mesenchymal stem cells together with possibilities of their isolation and cultivation. The main part of the text is formed by studies and methods used for targeted differentiation of mesenchymal stem cells and attempts of their transdifferentiation into neural cell line, together with present and possible future application of these cells in central nervous system therapies.Department of Cell BiologyKatedra buněčné biologieFaculty of SciencePřírodovědecká fakult

Results of a statistical evaluation of the Neogene in Hungary

Abstract The present study summarizes the results of formation-statistical investigations for the entire territory of Hungary, complementing the previous partial data in several directions, using methods that have been further developed. The most important sections of the study deal with –the basic conceptual and methodological questions of quantitative investigations; –the vertical evaluation of the Neogene complex; –the lateral evaluation of the Neogene complex and its facies; –the presentation of the quantitative investigations according to regional units; –the designation of the locations of the facies areas, changing through time. On the basis of the vertical and lateral theoretical sections, the study documents the Hungarian Neogene by means of worm's-eye-facies and paleogeographic map series for six time periods. It is followed by the structural geologic, faciological and stratigraphic conclusions

The divergent effects of cdppb and cannabidiol on fear extinction and anxiety in a predator scent stress model of ptsd in rats

Post-traumatic stress disorder (PTSD) currently has no FDA-approved treatments that reduce symptoms in the majority of patients. The ability to extinguish fear memory associations is impaired in PTSD individuals. As such, the development of extinction-enhancing pharmacological agents to be used in combination with exposure therapies may benefit the treatment of PTSD. Both mGlu5 and CB1 receptors have been implicated in contextual fear extinction. Thus, here we tested the ability of the mGlu5 positive allosteric modulator 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) and cannabidiol (CBD) to reduce both conditioned and unconditioned fear. We used a predator-threat animal model of PTSD which we and others have previously shown to capture the heterogeneity of anxiety responses observed in humans exposed to trauma. Here, 1 week following a 10-min exposure to predator scent stress, rats were classified into stress-Susceptible and stress-Resilient phenotypes using behavioral criteria for elevated plus maze and acoustic startle response performance. Two weeks after classification, rats underwent 3 days of contextual fear extinction and were treated with vehicle, CDPPB or CBD prior to each session. Finally, the light-dark box test was employed to assess phenotypic differences and the effects of CDPPB and CBD on unconditioned anxiety. CDPBB but not CBD, reduced freezing in Susceptible rats relative to vehicle. In the light-dark box test for unconditioned anxiety, CBD, but not CDPPB, reduced anxiety in Susceptible rats. Resilient rats displayed reduced anxiety in the light-dark box relative to Susceptible rats. Taken together, the present data indicate that enhancement of mGlu5 receptor signaling in populations vulnerable to stress may serve to offset a resistance to fear memory extinction without producing anxiogenic effects. Furthermore, in a susceptible population, CBD attenuates unconditioned but not conditioned fear. Taken together, these findings support the use of predator-threat stress exposure in combination with stress-susceptibility phenotype classification as a model for examining the unique drug response profiles and altered neuronal function that emerge as a consequence of the heterogeneity of psychophysiological response to stress. © 2019 Shallcross, Hámor, Bechard, Romano, Knackstedt and Schwendt

The Divergent Effects of CDPPB and Cannabidiol on Fear Extinction and Anxiety in a Predator Scent Stress Model of PTSD in Rats

Post-traumatic stress disorder (PTSD) currently has no FDA-approved treatments that reduce symptoms in the majority of patients. The ability to extinguish fear memory associations is impaired in PTSD individuals. As such, the development of extinction-enhancing pharmacological agents to be used in combination with exposure therapies may benefit the treatment of PTSD. Both mGlu5 and CB1 receptors have been implicated in contextual fear extinction. Thus, here we tested the ability of the mGlu5 positive allosteric modulator 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) and cannabidiol (CBD) to reduce both conditioned and unconditioned fear. We used a predator-threat animal model of PTSD which we and others have previously shown to capture the heterogeneity of anxiety responses observed in humans exposed to trauma. Here, 1 week following a 10-min exposure to predator scent stress, rats were classified into stress-Susceptible and stress-Resilient phenotypes using behavioral criteria for elevated plus maze and acoustic startle response performance. Two weeks after classification, rats underwent 3 days of contextual fear extinction and were treated with vehicle, CDPPB or CBD prior to each session. Finally, the light-dark box test was employed to assess phenotypic differences and the effects of CDPPB and CBD on unconditioned anxiety. CDPBB but not CBD, reduced freezing in Susceptible rats relative to vehicle. In the light-dark box test for unconditioned anxiety, CBD, but not CDPPB, reduced anxiety in Susceptible rats. Resilient rats displayed reduced anxiety in the light-dark box relative to Susceptible rats. Taken together, the present data indicate that enhancement of mGlu5 receptor signaling in populations vulnerable to stress may serve to offset a resistance to fear memory extinction without producing anxiogenic effects. Furthermore, in a susceptible population, CBD attenuates unconditioned but not conditioned fear. Taken together, these findings support the use of predator-threat stress exposure in combination with stress-susceptibility phenotype classification as a model for examining the unique drug response profiles and altered neuronal function that emerge as a consequence of the heterogeneity of psychophysiological response to stress

Palaeoenvironmental reconstruction of the Sarmatian (Middle Miocene) Central Paratethys based on palaeontological and geochernical analyses of foraminifera, ostracods, gastropods and rodents

International audiencePaleoenvironmental changes in the upper Middle Miocene Central Parathetys were reconstructed by using qualitative and quantitative palaeontological analyses of foraminifera and ostracods, coupled with trace elemental (Mg/Ca) and stable isotope (delta(18)O and delta(13)C) analyses of their carbonate skeletons and of gastropod sheets. Mean annual air temperatures were estimated using the oxygen isotope composition of contemporaneous rodent teeth. The studied aquatic fossils come from two boreholes in the Zsambek basin (northern central Hungary), while the terrestrial ones are from localities in NE Hungary and E Romania. In the studied Sarmatian successions, three zones could be distinguished, based on palaeontological and geochemical results. At the Badenian/Sarmatian boundary, faunal diversity decreased markedly. In the lower zone a transgressive event culminated in a seawater incursion into the semi-open basin system of the Central Paratheys. Stable bottom-water temperature (similar to 15 degrees C) and variable salinites (20-22\%) are estimated for the Early Sarmatian Sea. The faunal changes (notably a strong reduction in biodiversity) occuring at the boundary between the lower and the middle zone can be explained by a sea-leval highstand with dysoxic conditions. A relative sea-level fall is documented at the end of this middle zone. After a short regressive event, a marine connection between the Paratethys and Mediterranean was established at the beginning of the upper zone. This is indicated by an increased microfaunal diversity and the re-appearance of marine Bademan ostracods and foraminifera, which are completely absent from the older Samatian series. During the upper zone, the temperatures and salmities are estimated to have fluctuated from 15 degrees C to 21 degrees C and from 15 parts per thousand to 43 parts per thousand, respectively