Systemic Administration of CpG Oligodeoxynucleotide and Levamisole as Adjuvants for Gene-Gun-Delivered Antitumor DNA Vaccines

DNA vaccines showed great promise in preclinical models of infectious and malignant diseases, but their potency was insufficient in clinical trials and is needed to be improved. In this study, we tested systemic administration of two conventional adjuvants, synthetic oligodeoxynucleotide carrying immunostimulatory CpG motifs (CpG-ODN) and levamisole (LMS), and evaluated their effect on immune reactions induced by DNA vaccines delivered by a gene gun. DNA vaccination was directed either against the E7 oncoprotein of human papillomavirus type 16 or against the BCR-ABL1 oncoprotein characteristic for chronic myeloid leukemia. High doses of both adjuvants reduced activation of mouse splenic CD8+ T lymphocytes, but the overall antitumor effect was enhanced in both tumor models. High-dose CpG-ODN exhibited a superior adjuvant effect in comparison with any combination of CpG-ODN with LMS. In summary, our results demonstrate the benefit of combined therapy with gene-gun-delivered antitumor DNA vaccines and systemic administration of CpG-ODN or LMS

Hierarchical accumulation of RyR post-translational modifications drives disease progression in dystrophic cardiomyopathy

Aims Duchenne muscular dystrophy (DMD) is a muscle disease with serious cardiac complications. Changes in Ca2+ homeostasis and oxidative stress were recently associated with cardiac deterioration, but the cellular pathophysiological mechanisms remain elusive. We investigated whether the activity of ryanodine receptor (RyR) Ca2+ release channels is affected, whether changes in function are cause or consequence and which post-translational modifications drive disease progression. Methods and results Electrophysiological, imaging, and biochemical techniques were used to study RyRs in cardiomyocytes from mdx mice, an animal model of DMD. Young mdx mice show no changes in cardiac performance, but do so after ∼8 months. Nevertheless, myocytes from mdx pups exhibited exaggerated Ca2+ responses to mechanical stress and ‘hypersensitive' excitation-contraction coupling, hallmarks of increased RyR Ca2+ sensitivity. Both were normalized by antioxidants, inhibitors of NAD(P)H oxidase and CaMKII, but not by NO synthases and PKA antagonists. Sarcoplasmic reticulum Ca2+ load and leak were unchanged in young mdx mice. However, by the age of 4-5 months and in senescence, leak was increased and load was reduced, indicating disease progression. By this age, all pharmacological interventions listed above normalized Ca2+ signals and corrected changes in ECC, Ca2+ load, and leak. Conclusion Our findings suggest that increased RyR Ca2+ sensitivity precedes and presumably drives the progression of dystrophic cardiomyopathy, with oxidative stress initiating its development. RyR oxidation followed by phosphorylation, first by CaMKII and later by PKA, synergistically contributes to cardiac deterioratio

Student Scientific Conference MUNI Pharm 2021

The Abstract Book is issued annualy on the occasion of the Student Scientific Conference. It consists of the scientific research project abstracts in the field of pharmacy, which are submitted and presented by the students and evaluated by the scientific committee

Cesta ke zdraví

Title in English: Journey to Health: Suggestions for the implementation of oncological prevention in teaching health education The methodological material “Journey to Health. Suggestions for the implementation of oncological prevention in teaching health education” is focused on the prevention of oncological diseases and it is intended for teachers of upper primary schools for teaching Health Education, eventually Biology. Cancer is nowadays one of the most common diseases. Prevention plays important role in decreasing the incidence of oncological diseases, therefore it is very important that the basic knowledge about prevention of oncological diseases be given to primary school pupils. The main purpose is to acquaint pupils with primary and secondary prevention of oncological diseases and to increase their health literacy in this area. The material includes a suggestion for 20 lessons. Each of them contains professional information for teachers’ theoretical preparation, suggestions for the lesson, a worksheet with solutions, and proposal activities on the topic

Whole-Genome and Chromosome Evolution Associated with Host Adaptation and Speciation of the Wheat Pathogen Mycosphaerella graminicola

The fungus Mycosphaerella graminicola has been a pathogen of wheat since host domestication 10,000–12,000 years ago in the Fertile Crescent. The wheat-infecting lineage emerged from closely related Mycosphaerella pathogens infecting wild grasses. We use a comparative genomics approach to assess how the process of host specialization affected the genome structure of M. graminicola since divergence from the closest known progenitor species named M. graminicola S1. The genome of S1 was obtained by Illumina sequencing resulting in a 35 Mb draft genome sequence of 32X. Assembled contigs were aligned to the previously sequenced M. graminicola genome. The alignment covered >90% of the non-repetitive portion of the M. graminicola genome with an average divergence of 7%. The sequenced M. graminicola strain is known to harbor thirteen essential chromosomes plus eight dispensable chromosomes. We found evidence that structural rearrangements significantly affected the dispensable chromosomes while the essential chromosomes were syntenic. At the nucleotide level, the essential and dispensable chromosomes have evolved differently. The average synonymous substitution rate in dispensable chromosomes is considerably lower than in essential chromosomes, whereas the average non-synonymous substitution rate is three times higher. Differences in molecular evolution can be related to different transmission and recombination patterns, as well as to differences in effective population sizes of essential and dispensable chromosomes. In order to identify genes potentially involved in host specialization or speciation, we calculated ratios of synonymous and non-synonymous substitution rates in the >9,500 aligned protein coding genes. The genes are generally under strong purifying selection. We identified 43 candidate genes showing evidence of positive selection, one encoding a potential pathogen effector protein. We conclude that divergence of these pathogens was accompanied by structural rearrangements in the small dispensable chromosomes, while footprints of positive selection were present in only a small number of protein coding genes

XXV. mezinárodní kolokvium o regionálních vědách

Title in English: 25th International Colloquium on Regional Sciences: Conference proceedings The conference proceedings consists of papers presented at the 25th International Colloquium on Regional Sciences that was organized by Department of Regional Economics and Administration FEA MU. It contains 57 articles arranged by topic. The individual articles deal with e.g. socioeconomic disparities among regions, regional policy, territory attractiveness, tourism, or regional public administration

Sociálně patologické jevy u mládeže (toxikomanie) pokus o sociologickou diagnosu a možnosti sociální terapie

Katedra sociologieFilozofická fakult

The issue of an offender's personality in criminology

of the thesis "The issue of perpetrator personality in criminology" The purpose of the thesis is to analyse the personality of perpetrators and their criminal motivation. Special atention is payed to the different reasons of their criminal behavior. The thesis consists of the two main parts: the first one is theoretical and provides a base for the second part, which is concerned with a particular criminal case. Chapter one defines basic terminology, used in this thesis. It deals with problems between terminology, used in criminal law and in criminology. Chapter two focuses on theories that evolved throughout the history, in order to understand particular criminal behavior. Chapter three is about modern approach to study the perpetrators' personality, used in forensic psychology. The following chapter concerns the criminal motivation and points out some of the problems that terminology differences may cause. It reveals that on the field of criminal law, we often see an outdated terminology, in comparison with psychology, which does implicate problems in practice. Chapter five describes the capital crime - the murder. It deals with the contemporary Czech legislation and the classification of murders. Chapter six is divided into three parts, which are all related to the topic of serial murders; the..