24 research outputs found
Systematic and quantitative analysis of stop codon readthrough in Rett syndrome nonsense mutations
No full textLebeda D, Fierenz A, Werfel L, Rosin-Arbesfeld R, Hofhuis J, Thoms S. Systematic and quantitative analysis of stop codon readthrough in Rett syndrome nonsense mutations. Journal of Molecular Medicine. 2024;102:641–653.Rett syndrome (RTT) is a neurodevelopmental disorder resulting from genetic mutations in the methyl CpG binding protein 2 (MeCP2) gene. Specifically, around 35% of RTT patients harbor premature termination codons (PTCs) within the MeCP2 gene due to nonsense mutations. A promising therapeutic avenue for these individuals involves the use of aminoglycosides, which stimulate translational readthrough (TR) by causing stop codons to be interpreted as sense codons. However, the effectiveness of this treatment depends on several factors, including the type of stop codon and the surrounding nucleotides, collectively referred to as the stop codon context (SCC). Here, we develop a high-content reporter system to precisely measure TR efficiency at different SCCs, assess the recovery of the full-length MeCP2 protein, and evaluate its subcellular localization. We have conducted a comprehensive investigation into the intricate relationship between SCC characteristics and TR induction, examining a total of 14 pathogenic MeCP2 nonsense mutations with the aim to advance the prospects of personalized therapy for individuals with RTT. Our results demonstrate that TR induction can successfully restore full-length MeCP2 protein, albeit to varying degrees, contingent upon the SCC and the specific position of the PTC within the MeCP2 mRNA. TR induction can lead to the re-establishment of nuclear localization of MeCP2, indicating the potential restoration of protein functionality. In summary, our findings underscore the significance of SCC-specific approaches in the development of tailored therapies for RTT. By unraveling the relationship between SCC and TR therapy, we pave the way for personalized, individualized treatment strategies that hold promise for improving the lives of individuals affected by this debilitating neurodevelopmental disorder. KEY MESSAGES: The efficiency of readthrough induction at MeCP2 premature termination codons strongly depends on the stop codon context. The position of the premature termination codon on the transcript influences the readthrough inducibility. A new high-content dual reporter assay facilitates the measurement and prediction of readthrough efficiency of specific nucleotide stop contexts. Readthrough induction results in the recovery of full-length MeCP2 and its re-localization to the nucleus. MeCP2 requires only one of its annotated nuclear localization signals. © 2024. The Author(s)
The influence of electoral systems on party systems. Comparison of Polish, Slovak, German and Austrian Case.
No full textThe author is interested in electoral and political system in Poland, Slovakia, Germany and Austria. At the beginning he rises two basic questions which he would like to answer - Which electoral method is similar to contemporary electoral systems in chosen countries in a result? And how would be changed political-party- system, i f there were another electoral methods? In the General the author offers a detailed look at the analysis of the types of electoral systems, franchise and party systems. This General part is assumption for the Special part which is focused on an research. In the fourth Chapter the author describes electoral systems in Poland, Slovakia, Germany and Austria and in the fifth Chapter he describes party system in those chosen countries. The own research starts in the sixth chapter. The author analyses the results of the last election in Poland (2005), Slovakia (2006), Germany (2005) and Austria (2006) by index of deformation, index Loosemore - Hanby, and index of aggregation. In the next Chapters author analyses parliamentary electoral results in four countries, then he follows new electoral methods (D'Hondt, Imperiáli, Saint Laguě, Hare, Hagenbach-Bischoff) on those results in Poland (2005), Slovakia (2006), Germany (2005) and Austria (2006). In the last Chapter author resumes the..
Influence of single transferable vote on intraparty competition in the Republic of Ireland
No full textThe thesis deals with working of single transferable vote electoral system and its effects on political system. First the system is introduced and subsequently the main benefits and deficiencies are identified. The thesis especially aims at its effects on relations between political actors, specifically at Dáil elections in Ireland. Primary focus is laid on clarifying the relation among Dáil candidates from the same party. Among them a phenomenon called intra- party competition appears. The author searches if the single transferable vote is responsible, examines the nature of the conflict and describes the consequences for relations within parties. Secondary the author focuses on the nature of relations between candidates or deputies and their constituents. He examines, if the transferable vote is responsible for increased closeness of those relations, and for significant concentration of deputies on constituency work. The author uses clientelism and brokerage concepts. The last part of the thesis deals with political parties in context of the single transferable vote. The influence on cohesion, party discipline and relations of the party centers to candidates and deputies is examined. The thesis also concerns certain tensions between party centers and local structures
Interim governments in Czechoslovakia and the Czech Republic
No full textThe purpose of the study is to analyze the caretaker governments in the Czechoslovak and Czech political system. The thesis is divided into four parts. The first chapter focuses on the theory, and creation of a definition and typology of caretaker governments. The second part of the paper is dedicated to the research of Czechoslovak caretaker governments at the time of the so-called First republic (in years 1918-1926). The goal of the third chapter is to examine two Czechoslovak federal governments (1989-1992). The purpose of the last part of the thesis is to analyze two caretaker governments in the Czech republic (1993-2010). The aim of the research is to identify particular caretaker government in the context and contribute to deeper knowledge rather than generalize the findings. Author seeks to answer the question whether the caretaker governments represent negative feature of the Czech and Czechoslovak political system
Differences in voting in the Parliament of the Czech Republic: senators and their relation to political parties
No full textAuthor's thesis is concerned with differences between voting of parliamentary party groups within both chambers of Czech Parliament, Chamber of Deputies and Senate. It primarily focuses on senators and their relation to their respective parties. Author articulates three main hypothesis which he is trying to verify. Firstly, he anticipates senators to be less bounded to their parties than deputies. Secondly, he suggests that parliamentary party groups in both chambers become more united when it comes to more important voting. Lastly, the author considers the number of seats of parties in government in the Senate has no influence on either stability or legislative initiatives of the government. The theoretical part briefly describes Parliament of the Czech Republic, its composition, the role of the chambers and the legislative process. It also introduces outcomes of research made by Sociological Institute of Academy of Science of the Czech Republic in Parliament aimed at examining the role of deputies and senators from their own perspective. Also, the study "The Importance of Concurrence: The Impact of Bicameralism on Government Formation and Duration" by James N. Druckman and Michael F. Thies is presented. The analytical part extrapolates the main outcomes of analysis made and brings answers related to the..
Election Strategy of Small Political Parties: Case Study on TOP 09, Public Affairs Party and Party of Civic Rights - Zemanovci before Czech Parliamentary Elections 2010
No full textDiploma thesis Election Strategy of Small Political Parties: Case Study on TOP 09, Public Affairs Party and Party of Civic Rights - Zemanovci before Czech Parliamentary Elections 2010 assesses the election campaign of mentioned political parties, their personal, communication and financial strategy as well as their strategy of inter-parties relations. The author assumes that the small political parties, which all of the examined ones were at the time of this research, lead the campaign in a similar way - avoiding the negative campaign, they are led by a strong and well-known personality who can attract the attention not only of the voters but also of the media, and they have a large number of supporters who sympathize with the particular political entity. The theoretical concept of the text is based on the similarity of political and economic approach of marketing - therefore the author reckons the small political parties as the nichers of the political market. They can be characterized by occupying only a small niche of the political market which is ignored by the bigger political parties for those it is place of peripheral importance. Hence the basis of electoral campaign of any small political party is delineation unoccupied part of the market. Nevertheless it is crucial to simultaneously..
The Role of Regions in the Political System of the Czech Republic
No full textThe goal of this thesis is to analyse development of regions in the Czech republic as higher territorial administrative units. The analysis refers to the attitudes of the relevant political parties for their creation, the government's attitude towards the reform of public administration, which led to the creation of higher territorial administration units, i.e. counties, and last but not least author intends to compare the most important draft laws concerning the creation VÚSC. Powered by TCPDF (www.tcpdf.org
Evaluation of Effective Heat Transport and Temperature Gradients in Thermally Anisotropic Particulate Arrangements
No full textNew materials are
often designed to possess anisotropic
properties
to meet the specific demands of challenging applications. Thermally
anisotropic materials are particularly important in the thermal management
of electronics. Using anisotropic fillers is a common strategy to
tailor the thermal transport properties of macroscopic materials.
Various studies have demonstrated the role of filler concentration
on the effective material properties. Strikingly, little is known
about the contribution of the filler microstructure. Here, we study
anisotropic filler particles in a 2D composite material. We determined
the two main effects caused by the anisotropy. First, we show that
the thermal percolation behavior changes drastically depending on
the particle orientation. This enables the design of granular composites
with widely adjustable effective thermal conductivities governed by
composition and orientation. Second, we observe strong differences
in local temperature distributions between isotropic and anisotropic
mixtures. The admixture of anisotropic constituents leads to strong
internal temperature gradients. These are unfavorable for many thermal
management applications. Consequently, anisotropy can control the
effective heat transport in composite materials, but adverse temperature
gradients need to be considered
Canoeing courses in secondary schools in the Central region
No full textTheme of this thesis is to determine the current state of canoeing courses organized by secondary schools in the Central region. Thesis is focused on the detailed arrangements of courses, their organization and other information associated with this. The author also tries form the information and legislative facts to determine how it should ideally look like such a course
