Adenosine A2A receptor ligand recognition and signaling is blocked by A2B receptors

The adenosine receptor (AR) subtypes A2A and A2B are rhodopsin-like Gs protein-coupled receptors whose expression is highly regulated under pathological, e.g. hypoxic, ischemic and inflammatory conditions. Both receptors play important roles in inflammatory and neurodegenerative diseases, are blocked by caffeine, and have now become major drug targets in immuno-oncology. By Förster resonance energy transfer (FRET), bioluminescence resonance energy transfer (BRET), bimolecular fluorescence complementation (BiFC) and proximity ligation assays (PLA) we demonstrated A2A-A2BAR heteromeric complex formation. Moreover we observed a dramatically altered pharmacology of the A2AAR when co-expressed with the A2BAR (A2B ≥ A2A) in recombinant as well as in native cells. In the presence of A2BARs, A2A-selective ligands lost high affinity binding to A2AARs and displayed strongly reduced potency in cAMP accumulation and dynamic mass redistribution (DMR) assays. These results have major implications for the use of A2AAR ligands as drugs as they will fail to modulate the receptor in an A2A-A2B heteromer context. Accordingly, A2A-A2BAR heteromers represent novel pharmacological targets

Obama's Pivot to Asia and Its Impact on U.S.-Korea Relations

Katedra severoamerických studiíDepartment of North American StudiesFaculty of Social SciencesFakulta sociálních vě

Managerial skills

The theoretical basis of this thesis explains the terms closely associated with the management and managerial skills. Introductory part relates to approach the concept itself and the executive management, we are further broken down managerial functions, which are continuously illuminates to describe other skills, such as communication, goal setting, skills and coaching. The main point is to approach the concepts of soft and hard skills that managers should possess, or which should in the course of his practice to learn. Only by careful control of both of these groups of skills can lead to good organization. For a clearer explanation of the managerial skills included graphic view, which approximates the distribution of skills. In the second part, a practical part, described the situation with the existing skills of managers in the selected company. Thanks to the questionnaire, it is possible to measure the current level of acquired skills of managers at three levels and can be evaluated, what is the interest of improving individual skills, or whether managers feel sufficiently qualified for their job positions

Accountig Treatment of Specific Cases in Limited Liability Company in CR

This bachelor thesis is focused on the accounting practises of specific cases in business company, specifically in the limited liability company in accordance with Czech law. The work describes the characteristics of this legal form, the conditions for the establishment and creation, organizational structure, the relationships between the company and shareholders and capital operations with a focus on the economic outcome. The practical part analyses concrete limited liability company, starting with the performance of the company by using the basic data, open the accountancy books and accounting processes in the concrete limited liability company. The central part of practical part is compile summary of the structure of property, sources of financing, income and expenses resulting from the balance sheet and the profit and loss account for the reference period. The end of this bachelor thesis is evalueting the situation and compare the ascertained results

Genetic polymorphism in the HFE gene in the Czech population

Univerzita Karlova v Praze Farmaceutická fakulta v Hradci Králové Katedra biochemických věd Kandidát: Bc. Barbora Červinková Školitel: Doc. PharmDr. Martin Beránek, Ph.D. Název diplomové práce: Genetický polymorfismus v HFE genu v české populaci. Cíl práce: Cílem diplomové práce bylo zmapovat výskyt třech mutací v HFE genu (C282Y, H63D, S65C) u české populace. A následně porovnat získané výsledky s hodnotami hlášenými ze světa. Metody: Práce zahrnovala izolaci DNA ze stěrů bukální sliznice od 167 dárců (65 mužů, 102 žen; věkový průměr mužů byl 31 a žen 28). Získaná DNA byla následně zmnožena prostřednictvím metody PCR za použití primerů 5'-CAG ATC CTC ATC TCA CTG- 3' a 5'-CTG GAT AAC CTT GGC TGT ACC CCC - 3' pro C282Y mutaci, 5'-GCC ACA TCT GGC TTG AAA TT-3' a 5'-ACA TGG TTA AGG CCT GTT GC GCC ACA-3' primerů pro H63D a S65C mutace. Pomocí restrikčního enzymu Rsa I pro C282Y, Bcl I pro H63D, Hinf I pro S65C byl řetězec DNA rozštěpen a získané fragmenty byly odseparovány na 2 % agarózovém gelu metodou gelové elektroforézy. Výsledky: Mutace C282Y byla detekována u 0 (0 %) vzorků jako homozygot, u 3 (1,80 %) vzorků jako složený heterozygot s H63D, u 0 (0 %) vzorků jako složený heterozygot s S65C a u 19 (11,38 %) vzorků, jako samostatná mutace v kombinaci se zdravou alelou. Mutace H63D byla detekována u...Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Barbora Červinková Supervisor: Doc. PharmDr. Martin Beránek, Ph.D. Title of diploma work: Genetic polymorphism of the HFE gene in Czech population Outline: The main objective of the thesis was to map the incidence of the three mutations (C282Y, H63D, S65C) in the HFE gene in the Czech population. Consequently, the obtained results were compared with the reported occurrence in the world. Methods: The work involved the isolation of DNA from buccal swabs obtained from 167 donors (65 men, 102 women; average age for men was 31, for women 28). Isolated DNA strings were amplified by PCR methods using 5'-CAG ATC CTC ATC TCA CTG-3' and 5'-CTG GAT AAC CTT GGC TGT ACC CCC-3' primers for C282Y mutation, 5'-GCC ACA TCT GGC TTG AAA TT-3' and 5'-ACA TGG TTA AGG CCT GTT GC GCC ACA- 3' primers for H63D and S65C mutations. DNA samples were treated with restriction enzymes Rsa I, Bcl I and Hinf I, for C282Y, H63D and S65C mutations, respectively. Finally, the restriction fragments were separated by gel electrophoresis (2 % agarose gel). Results: C282Y mutation was present in 0 (0 %) and 19 (11,38 %) samples as homozygote or heterozygote, respectively. Moreover, C282Y mutation was present in 3 (1,80 %)...Department of Biochemical SciencesKatedra biochemických vědFaculty of Pharmacy in Hradec KrálovéFarmaceutická fakulta v Hradci Králov

Genetic polymorphism in the HFE gene in the Czech population

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Barbora Červinková Supervisor: Doc. PharmDr. Martin Beránek, Ph.D. Title of diploma work: Genetic polymorphism of the HFE gene in Czech population Outline: The main objective of the thesis was to map the incidence of the three mutations (C282Y, H63D, S65C) in the HFE gene in the Czech population. Consequently, the obtained results were compared with the reported occurrence in the world. Methods: The work involved the isolation of DNA from buccal swabs obtained from 167 donors (65 men, 102 women; average age for men was 31, for women 28). Isolated DNA strings were amplified by PCR methods using 5'-CAG ATC CTC ATC TCA CTG-3' and 5'-CTG GAT AAC CTT GGC TGT ACC CCC-3' primers for C282Y mutation, 5'-GCC ACA TCT GGC TTG AAA TT-3' and 5'-ACA TGG TTA AGG CCT GTT GC GCC ACA- 3' primers for H63D and S65C mutations. DNA samples were treated with restriction enzymes Rsa I, Bcl I and Hinf I, for C282Y, H63D and S65C mutations, respectively. Finally, the restriction fragments were separated by gel electrophoresis (2 % agarose gel). Results: C282Y mutation was present in 0 (0 %) and 19 (11,38 %) samples as homozygote or heterozygote, respectively. Moreover, C282Y mutation was present in 3 (1,80 %)..

Life with multiple sklerosis

Roztroušená skleróza je autoimunitní onemocnění centrální nervové soustavy postihující především dospělé v produktivním věku, častěji ženy než muže. Choroba ovlivňuje dosavadní život pacienta a jeho blízkých. Bakalářská práce na téma: "Život s roztroušenou sklerózou" je rozdělena na teoretickou a praktickou část. Teoretická část se zabývá definicí, historií, patogenezí, etiologií, rizikovými faktory, diagnostikou, typy průběhů. režimovými opatřeními a rolí specializované všeobecné sestry. Praktická část představuje výsledky výzkumného šetření, které probíhalo od prosince 2016 do března 2017.ObhájenoMultiple sclerosis is an autoimmune disease of central nervous system, vhich mainly affects adults in productive age, more likely women then men. The disease affects life of a patient himself as well as his family members. Thesis in the topic: "Life with multiple sclerosis" is divided into theoretical and practical part. The theoretical part deals with definition, history, pathogenesis, etiology, risk factors, diagnosis, types of disease course, treatment, pregnancy, lifestyle changes and a role of a specially trained nurse. Practical part presents results of research, which were conducted since December 2016 to March 2017

Women awareness of breast cancer prevention

Prevention of breast cancer using the form of mammographic screening is one of the most important factors involved in early diagnosis and reduction of mortality with this type of cancer, which is the most frequently occurring cancer in women in the Czech Republic. The aim of the study was to investigate the previous use of screening and preventative measures by women who subsequently were diagnosed by breast cancer. The survey was conducted through a voluntary, anonymous questionnaire survey of 166 randomly selected patients attending an outpatient clinic for patients with breast CA. Main hypotheses of bachelor thesis: 1) More than 50% of the women tested were informed of the recommendation to regularly take part in screening examinations carried out as a part of the breast cancer screening (mammography examination). 2) More than 50% of the females tested regularly (repeatedly) participated in screening examination carried out as a part of the breast cancer screening (mammography examination). 3) More than 50% of the females tested underwent breast examination outside of the breast screening (sonography). 4) More than 50% of the tested females from the group regularly performed self- examination of the breasts (palpation examination). The established hypotheses were not met. However, the result is..

Obama's Pivot to Asia and Its Impact on U.S.-Korea Relations

Katedra severoamerických studiíDepartment of North American StudiesFaculty of Social SciencesFakulta sociálních vě