From the search for new oncogenes to the effort of redefining the cancerogenesis phenomenon

The described experimental model of clonal tumors induced through the insertional mutagenesis with MAV-2 proved to be a valid and rich source of information describing the process of transformation of normal into tumor cell. We have mapped more than 2000 individual clonal VISs from several hundreds of tumor tissue samples. We have analyzed five tumor types of different histology and tissue of origin along with their derivative tissue cultures. Furthermore, we have discovered the industasis phenomenon and described it during the course of the study. The goal of my study was to uncover common reasons for neoplastic transformation of the cell. The results of my study led me to the paradoxical conclusion that the significance of genetic changes as the primary cause of induction of neoplastic transformation is being overestimated. Although studying the functions of individual genes and search for new tumor markers and therapeutical targets are still beneficial, I believe that the traditional perception of tumor formation as a function/result of mutation accumulation and selection is becoming a serious drawback in further investigations. These conclusions are further discussed in the last section of the presented Ph.D. thesis

Characterization of Two Historic Smallpox Specimens from a Czech Museum

Although smallpox has been known for centuries, the oldest available variola virus strains were isolated in the early 1940s. At that time, large regions of the world were already smallpox-free. Therefore, genetic information of these strains can represent only the very last fraction of a long evolutionary process. Based on the genomes of 48 strains, two clades are differentiated: Clade 1 includes variants of variola major, and clade 2 includes West African and variola minor (Alastrim) strains. Recently, the genome of an almost 400-year-old Lithuanian mummy was determined, which fell basal to all currently sequenced strains of variola virus on phylogenetic trees. Here, we determined two complete variola virus genomes from human tissues kept in a museum in Prague dating back 60 and 160 years, respectively. Moreover, mass spectrometry-based proteomic, chemical, and microscopic examinations were performed. The 60-year-old specimen was most likely an importation from India, a country with endemic smallpox at that time. The genome of the 160-year-old specimen is related to clade 2 West African and variola minor strains. This sequence likely represents a new endemic European variant of variola virus circulating in the midst of the 19th century in Europe

Motivace zaměstnanců v organizaci

Práce se zabývá moderním pojetím personálních činností v podniku, přičemž je zaměřena především na oblast motivace zaměstnanců, jakožto oblast, jejíž význam je v rámci vykonávaných personálních činností v podniku velmi vysoký. Na teoretický základ obsahující právě popis činností útvaru lidských zdrojů ve firmě, vysvětlení pojmu motivace, vývoj přístupů k motivaci v průběhu minulého století, zdroje motivace a popis prostředků ke zvýšení motivovanosti zaměstnanců (stimulačních prostředků), navazuje část praktická, která má za úkol zhodnotit motivovanost a sociální situaci ve zvolené firmě a zároveň přinést určitá doporučení, či náměty pro zlepšení současného stavu. Výsledky a doporučení mají obecnou platnost, a jsou využitelné i pro další subjekty, které se otázkou motivovanosti zaměstnanců zabývají

Analyse of company culture of Dřevozpracující družstvo

Master thesis is concerned on analyse of company culture of Dřevozrpacující družstvo Lukavec. Company culture of DDL has been tested from three levels - level of basic values, level of standards and level of symbols. For research have been used social audits and intern materials of DDL, and my own research as well. The conclusion of thesis should be very usefull for management of the company like a managing material containing and stressing some elements, which influece the company culture of DDL

From the search for new oncogenes to the effort of redefining the cancerogenesis phenomenon

The described experimental model of clonal tumors induced through the insertional mutagenesis with MAV-2 proved to be a valid and rich source of information describing the process of transformation of normal into tumor cell. We have mapped more than 2000 individual clonal VISs from several hundreds of tumor tissue samples. We have analyzed five tumor types of different histology and tissue of origin along with their derivative tissue cultures. Furthermore, we have discovered the industasis phenomenon and described it during the course of the study. The goal of my study was to uncover common reasons for neoplastic transformation of the cell. The results of my study led me to the paradoxical conclusion that the significance of genetic changes as the primary cause of induction of neoplastic transformation is being overestimated. Although studying the functions of individual genes and search for new tumor markers and therapeutical targets are still beneficial, I believe that the traditional perception of tumor formation as a function/result of mutation accumulation and selection is becoming a serious drawback in further investigations. These conclusions are further discussed in the last section of the presented Ph.D. thesis

From the search for new oncogenes to the effort of redefining the cancerogenesis phenomenon

The described experimental model of clonal tumors induced through the insertional mutagenesis with MAV-2 proved to be a valid and rich source of information describing the process of transformation of normal into tumor cell. We have mapped more than 2000 individual clonal VISs from several hundreds of tumor tissue samples. We have analyzed five tumor types of different histology and tissue of origin along with their derivative tissue cultures. Furthermore, we have discovered the industasis phenomenon and described it during the course of the study. The goal of my study was to uncover common reasons for neoplastic transformation of the cell. The results of my study led me to the paradoxical conclusion that the significance of genetic changes as the primary cause of induction of neoplastic transformation is being overestimated. Although studying the functions of individual genes and search for new tumor markers and therapeutical targets are still beneficial, I believe that the traditional perception of tumor formation as a function/result of mutation accumulation and selection is becoming a serious drawback in further investigations. These conclusions are further discussed in the last section of the presented Ph.D. thesis.Zvolený experimentální model indukce klonálních nádorů inzerční mutagenezí MAV-2 se ukázal být velmi cenným a bohatým zdrojem informací o procesu transformace normální buňky v buňku nádorovou. V souhrnu bylo mapováno více než 2000 individuálních klonálních VIS z několika set nádorových vzorků. Bylo molekulárně analyzováno 5 tkáňově a histologicky odlišných nádorových typů a od nich odvozených tkáňových kultur. Při studiu byl objeven a popsán fenomén industáze. Hlavním cílem této práce však bylo pochopit obecné důvody a příčiny nádorové transformace buňky. Výsledky studia vedly autora k poněkud paradoxnímu tvrzení, že význam genetických změn v transformované buňce je přeceňován. Přestože popisování funkce jednotlivých genů, hledání nádorových markerů a molekulárních cílů pro terapii je stále velmi přínosné, domnívá se, že tradiční představa vzniku nádoru jako funkce hromadění mutací a jejich selekce je v současnosti významnou brzdou dalšího výzkumu. Úvahy na toto téma jsou shrnuty v závěrečné části předkládané disertační práce.Department of Genetics and MicrobiologyKatedra genetiky a mikrobiologieFaculty of SciencePřírodovědecká fakult

Salmonella Paratyphi Infection: Use of Nanopore Sequencing as a Vivid Alternative for the Identification of Invading Bacteria

In our study we present an overview of the use of Oxford Nanopore Technologies (ONT) sequencing technology on the background of Enteric fever. Unlike traditional methods (e.g., qPCR, serological tests), the nanopore sequencing technology enables virtually real-time data generation and highly accurate pathogen identification and characterization. Blood cultures were obtained from a 48-year-old female patient suffering from a high fever, headache and diarrhea. Nevertheless, both the initial serological tests and stool culture appeared to be negative. Therefore, the bacterial isolate from blood culture was used for nanopore sequencing (ONT). This technique in combination with subsequent bioinformatic analyses allowed for prompt identification of the disease-causative agent as Salmonella enterica subsp. enterica serovar Paratyphi A. The National Reference Laboratory for Salmonella (NIPH) independently reported this isolate also as serovar Paratyphi A on the basis of results of biochemical and agglutination tests. Therefore, our results are in concordance with certified standards. Furthermore, the data enabled us to assess some basic questions concerning the comparative genomics, i.e., to describe whether the isolated strain differs from the formerly published ones or not. Quite surprisingly, these results indicate that we have detected a novel and so far, unknown variety of this bacteria