Mutations in the human LMNA gene encoding A-type lamins cause a collection of diseases termed laminopathies, including several types of muscular dystrophy. Lamins are intermediate filaments, which line the inner membrane of nuclear envelope. Lamins maintain the nuclear shape and regulate gene expression through interactions with chromatin. Heterozygous mutations LMNA, which result in single amino acid substitutions within the C-terminal Ig-fold domain, were identified in patients with muscular dystrophy. These substitutions were modeled in Drosophila and found to cause muscle defects. We have taken a multi-disciplinary approach to understanding the molecular basis of these muscle defects. Using Nuclear Magentic Resonance (NMR) and Circular Dischroism (CD) we determined that the amino acid substitutions cause perturbations of the tertiary, but not secondary, structure of the Ig-fold. Microarray analysis of RNA isolated from muscle revealed that mutant lamins cause cause mis-regulation of genes involved oxidative stress and neuromuscular junction function. Collectively, these data demonstrate that perturbations within the lamin Ig-fold cause changes in gene expression, providing insights on pathways involved in pathogenesis and identifying new potential therapeutic targets.

The subject of this diploma thesis is the elaboration of a construction and technological project of production and storage hall SW-MOTECH s.r.o., in which the technical report, coordination of broader transport relations, time and financial plan of the construction, study of the main technological stages, project of building equipment, design of the main construction machines and mechanisms. Further, the thesis contains a technological regulation, a control and test plan and safety requirements for the implementation of reinforced concrete assembled structures. Part of the diploma thesis is also environmental plan and contract for work.

The diploma thesis deals with the issue of the building technology project of the structural work of industrial building belonging to CECHO company in Polnička. The industrial building consists of two building objects, shop floor and office building. The main aim of the thesis is to focus on the time and financial management of the construction, schedule, site equipment management including time schedule of establishment and removal of temporary site equipment objects and their rental costs, transport routes planning, proposal of main building equipment, oversized transport and technological regulations including inspection and test plans of quality. Last but not least, the thesis is also aimed at the itemized budget.