A humán ABCG2 multidrog transzporter működésének vizsgálata = Investigation of the mechanism of action of the human ABCG2 multidrug transporter

A humán ABCG2 egy plazma membrán glikoprotein, amely a szervezet méregtelenítésében játszik szerepet, ezen kívül ellenállóvá teheti a rákos sejteket bizonyos gyógyszerekkel szemben. Az ABCG2 az őssejtek egyik jellegzetes fehérjéje. Jelen kutatás során a következő főbb eredményeket értük el: 1. Változatos szubsztrát specificitással és transzport aktivitással bíró mutáns változatokat hoztunk létre a vad-típustól mindössze a 482-es aminosav pozícióban eltérő ABCG2 mutánsok előállításával, amelyek hasznosíthatók lehetnek például terápiás sejtek védelmében. 2. Igazoltuk, hogy az ABCG2-Q141K polimorfizmus csökkent aktivitással bír, ezért az ezt a változatot hordozó egyedek bizonyos gyógyszerekkel szemben érzékenyebbek lehetnek. 3. Kimutattuk, hogy az ABCG2 kölcsönhatásba lép egyes, a klinikumban használt tirozin kináz gátló gyógyszerekkel, tehát befolyásolhatja ezek hatékonyságát a kemoterápia során. 4. Elvégeztük egy ABCG2-specifikus antitest jellemzését, amely hasznosítható lehet tumoros mintákban lévő ABCG2 kimutatására, vagy akár őssejtek kiválogatására. 5. Kimutattuk, hogy a membrán koleszterin tartalma befolyásolja az ABCG2 transzporter aktivitását, tehát a fehérje működése különböző membrán kompartmentekbe történő lokalizációja illetve internalizációja által szabályozódhat. 6. Fluoreszcens ?címkével? ellátott ABCG2 fehérjét hoztunk létre, amellyel pl. ABCG2 szubsztrátok tesztelhetők élő sejtekben vagy lokalizációs vizsgálatok végezhetők. | Human ABCG2 is a plasma membrane glycoprotein that protects our body against toxic compounds. ABCG2 is also able to confer resistance against several drugs used in cancer chemotherapy. ABCG2 is a marker protein of stem cells. The main findings of our research are the following: 1) We have generated ABCG2 mutants having altered substrate specificity and transport activity by inducing single amino acid change at position 482. These mutants are ideal candidates to be used for protection of modified cells in medical gene therapy. 2) We have shown that the Q141K polymorphism of ABCG2 has decreased activity, therefore may result in altered pharmacokinetics of ABCG2 substrates and increase chemosensitivity in clinical oncology. 3) We have demonstrated that ABCG2 interacts with several clinically relevant tyrosine kinase inhibitors; therefore this protein may influence their effectiveness. 4) We have characterised an ABCG2-specific antibody that can be an important tool in detection of ABCG2 in clinical samples or in stem cell research. 5) We have shown that membrane cholesterol level influences the activity of ABCG2, therefore the localisation of ABCG2 e.g. in cholesterol rich rafts may have major impact on the activity of this transporter. 6) We have generated a cell line expressing functionally active, green fluorescence protein tagged ABCG2 that may be a useful tool for e.g. localisation studies or drug-screening in living cells

Az életünket átszövő statisztika

Numbers, data as well as statistics, are an integral elements of our daily lives and appear in all areas of economic and social processes, in researches and in all areas of science. Cooperation between geographers and statisticians was established in 2016, and has been expanding year by year. I was delighted that the geographers of the University of Szeged decided to organize a Section on Statistics at the conference organized in Szeged, in December 2019. The papers and lecturers - giving practical examples - reviewed the process of statistics, from data collection to the application of statistical methodologies. The section was an excellent example of cooperation between two sub-disciplines, showed examples on interaction in between and introduced examples on development and application of statistical methodologies in the geography science

Agrárcenzusok szerepe az agrárinformációs rendszerben (1895-2010)

A rendszeres mezÅ‘gazdasági adatgyűjtések közel kétszáz éves múltra tekintenek vissza. Az 1828-tól végrehajtott felmérések a földhasználatra, növénytermelésre és az állattartásra terjedtek ki, az elsÅ‘ „földhasználati regisztert†– az ideiglenes föld¬katasztert – 1853-ban állították fel. A szÅ‘lÅ‘területekre, borászatra vonatkozó elsÅ‘ statisztikát Magyarország – nemzetközi felkérésre – 1873-ban dolgozta ki, illetve hajtotta végre. A 19. század végére már Európa-szerte egyre nagyobb igény merült fel a mezÅ‘gazdasági tevékenység, a mezÅ‘gazdasági termelés részletesebb megismerésére. Az elsÅ‘ magyar – általános – mezÅ‘gazdasági cenzus rendszerét Keleti Károly, az önálló magyar statisztikai hivatal elsÅ‘ elnöke személyes vezetésével dolgozták ki. A nagy volumenű munka végrehajtására csak Keleti Károly halála után – 1895-ben – kerülhetett sor, mert a cenzus végrehajtása forrásainak megteremtése nagy nehé¬zségekbe ütközött. Az EU rendeletének megfelelÅ‘en 2010-ben teljes körű mezÅ‘gazdasági összeírásra, majd 2013-ban és 2016-ban reprezentatív mezÅ‘gazdasági össze’rásra kerül sor. ---------------------------------------------------- Regular collection of agricultural information goes back to nearly two hundred years. The surveys, which began in 1828, addressed land use, crop cultivation and animal husbandry. The first ‘land use register’ – a temporary cadastre – was set up in 1853. The first Hungarian statistics for viticulture and winemaking were created in 1873 upon international request. By the end of the 19th century, the need to obtain more detailed information about agricultural activities and agricultural production had grown substantially. The methodology for the first general agricultural census in Hungary was developed under the personal supervision of Károly Keleti, the first head of the first independent Hungarian Statistical Office. This ambitious job could only be completed after his death, in 1895, because of the great difficulties of obtaining funding for its implementation.statisztika, összeírás, információs rendszer, üzemszerkezet, agrártörténet, statistics, listing, information system, farm structure, agro-history, Agricultural and Food Policy,

The importance of steroid uptake and intracrine action in endometrial and ovarian cancers

Endometrial and ovarian cancers predominately affect women after menopause, and are more frequently observed in developed countries. These are considered to be hormone-dependent cancers, as steroid hormones, and estrogens in particular, have roles in their onset and progression. After the production of estrogens in the ovary has ceased, estrogen synthesis occurs in peripheral tissues. This depends on the cellular uptake of estrone-sulfate and dehydroepiandrosterone-sulfate, as the most important steroid precursors in the plasma of postmenopausal women. The uptake through transporter proteins, such as those of the organic anion-transporting polypeptide (OATP) and organic anion-transporter (OAT) families, is followed by the synthesis and action of estradiol E2. Here, we provide an overview of the current understanding of this intracrine action of steroid hormones, which depends on the availability of the steroid precursors and transmembrane transporters for precursor uptake, along with the enzymes for the synthesis of E2. The data is also provided relating to the selected transmembrane transporters from the OATP, OAT, SLC51, and ABC-transporter families, and the enzymes involved in the E2-generating pathways in cancers of the endometrium and ovary. Finally, we discuss these transporters and enzymes as potential drug targets. © 2017 Rižner, Thalhammer and özvegy-Laczka

Az ABCA1 membránfehérje funkciójának és fehérje-kölcsönhatásainak vizsgálata = Investigation of the function and protein interactions of the ABCA1 membrane protein

A kutatás célja az ABCA1 membránfehérje működésének és fehérje-kölcsönhatásainak jellemzése volt. Új modellrendszereket alakítottunk ki Sf9 rovarsejt-bakulovírus és retrovirális expressziós rendszerek segítségével, részletesen vizsgáltuk a vad-típusú és mutáns ABCA1 fehérjék sejten belüli lokalizációját, működését és PDZ fehérjékkel való kölcsönhatását. Bizonyítottuk, hogy az ABCA1 fehérje mind az ApoA1-függő koleszterin kiáramlás, mind a Ca2+-aktivált sejtfelszíni foszfatidilszerin expozíció folyamatában fontos szerepet játszik. Elsőként mutattunk ki összefüggést egy vérzékenységi betegség és az ABCA1 működése között. Elemeztük az ABCA1 mutációnak hatását a betegségre jellemző hibás foszfatidilszerin expozícióban. Vizsgáltuk a lipidanyagcserére ható vegyületek hatását az ABCA1-hez köthető funkciókra, azonosítottunk két új gátló vegyületet. Megállapítottuk, hogy egy speciális PDZ fehérje a vizsgált ABC fehérjék közül egyedül az ABCA1 fehérjével lép kölcsönhatásba, más ABC transzporterekhez kötő egyéb PDZ fehérjék nem kötődtek az ABCA1-hez. Kimutattuk polarizált sejtekben az ABCA1, a b2-syntrophin és az utrophin bazolaterális ko-lokalizációját. A kidolgozott mérési módszereket más ABC transzporterek működésének vizsgálatára is eredményesen alkalmaztuk. Megkezdtük a foszfolipid-transzportért felelős ABC fehérjék azonosítását trombocitákban. | The aims of this project were the functional characterization of the ABCA1 protein and identification of its potential interactions with intracellular proteins. We installed new assay systems to analyse the function, subcellular localization and protein interactions of the wild-type and mutant ABCA1 versions, by using two expression systems: the baculovirus-Sf9 insect cell system and retrovirus based expression system for mammalian cells. We proved that ABCA1 plays a key role both in cellular ApoAI-mediated cholesterol removal pathway, and in the exofacial translocation of phosphatidylserine. Our results provided the first link between a defect in a transbilayer phospholipid transport pathway, that of ABCA1, and the bleeding phenotype. We analysed the effects of various mutations of ABCA1 on the Ca2+-stimulated PS exposition. We screened the influence of potential inhibitors on the ABCA1-dependent processes and identified new inhibitors of the PS exposition. We demonstrated that among the examined ABC transporters only ABCA1 binds b2-syntrophin. A diverse group of PDZ proteins that interacts with other ABC proteins does not bind to ABCA1. We showed basolateral colocalization of ABCA1 protein with b2-syntrophin and utrophin. The assays for ABCA1 characterization were applied for studying other ABC proteins successfully. We started the identification of ABC proteins involved in phospholipid translocation in platelets

A statisztika helye, szerepe a kutatói munkában

Statistics is a scientific and practical activity on how to measure, process, analyse, model and interpret the numerical information on facts. The birth of Statistics dates back to the 18th century but if we take all numerical information into consideration gathered by former states it dates far beyond that. In order to provide a reliable picture on the facts, provide good quality statistical data statisticians and users must follow the changes of economic and social life and the changing environment. If we take only the impact of technical (IT) development, impact of globalisation into consideration took place in the past decades the data collection practice, methodology of statistics, data processing must be renewed again (it requires a paradigm shift in Statistics). My paper is going to present a few examples for users, researchers on how to analyse statistical data pointing out the advantages and disadvantages of our digital are

Surface immuno-functionalisation for the capture and detection of vibrio species in the marine environment: A new management tool for industrial facilities

© 2014 Laczka et al. Bacteria from the genus Vibrio are a common and environmentally important group of bacteria within coastal environments and include species pathogenic to aquaculture organisms. Their distribution and abundance are linked to specific environmental parameters, including temperature, salinity and nutrient enrichment. Accurate and efficient detection of Vibrios in environmental samples provides a potential important indicator of overall ecosystem health while also allowing rapid management responses for species pathogenic to humans or species implicated in disease of economically important aquacultured fish and invertebrates. In this study, we developed a surface immuno-functionalisation protocol, based on an avidin-biotin type covalent binding strategy, allowing specific sandwich-type detection of bacteria from the Vibrio genus. The assay was optimized on 12 diverse Vibrio strains, including species that have implications for aquaculture industries, reaching detection limits between 7×103 to 3×104 cells mL-1. Current techniques for the detection of total Vibrios rely on laborious or inefficient analyses resulting in delayed management decisions. This work represents a novel approach for a rapid, accurate, sensitive and robust tool for quantifying Vibrios directly in industrial systems and in the environment, thereby facilitating rapid management responses

Colorimetric detection of caspase 3 activity and reactive oxygen derivatives: Potential early indicators of thermal stress in corals

© 2016 Mickael Ros et al. There is an urgent need to develop and implement rapid assessments of coral health to allow effective adaptive management in response to coastal development and global change. There is now increasing evidence that activation of caspase-dependent apoptosis plays a key role during coral bleaching and subsequent mortality. In this study, a "clinical" approach was used to assess coral health by measuring the activity of caspase 3 using a commercial kit. This method was first applied while inducing thermal bleaching in two coral species, Acropora millepora and Pocillopora damicornis. The latter species was then chosen to undergo further studies combining the detection of oxidative stress-related compounds (catalase activity and glutathione concentrations) as well as caspase activity during both stress and recovery phases. Zooxanthellae photosystem II (PSII) efficiency and cell density were measured in parallel to assess symbiont health. Our results demonstrate that the increased caspase 3 activity in the coral host could be detected before observing any significant decrease in the photochemical efficiency of PSII in the algal symbionts and/or their expulsion from the host. This study highlights the potential of host caspase 3 and reactive oxygen species scavenging activities as early indicators of stress in individual coral colonies

Lipid Regulation of the ABCB1 and ABCG2 Multidrug Transporters

This chapter deals with the interactions of two medically important multidrug ABC transporters (MDR-ABC), ABCB1 and ABCG2, with lipid molecules. Both ABCB1 and ABCG2 are capable of transporting a wide range of hydrophobic drugs and xenobiotics and are involved in cancer chemotherapy resistance. Therefore, the exploration of their mechanism of action has major therapeutic consequences. As discussed here in detail, both ABCB1 and ABCG2 are significantly affected by various lipid compounds especially those residing in their close proximity in the plasma membrane. ABCB1 is capable of transporting lipids and lipid derivatives, and thus may alter the general membrane composition by "flopping" membrane lipid constituents, while there is no such information regarding ABCG2. Still, both ABCB1 and ABCG2 show complex interactions with a variety of lipid molecules, and the transporters are significantly modulated by cholesterol and cholesterol derivatives at the posttranslational level. In this chapter, we explore the molecular details of the direct transporter-lipid interactions, the potential role of lipid-sensor domains within the proteins, as well as the application of experimental site-directed mutagenesis, detailed structural studies, and in silico modeling for examining these interactions. We also discuss the regulation of ABCB1 and ABCG2 expression at the transcriptional level, occurring through nuclear receptors involved in lipid sensing. The better understanding of lipid interactions with these medically important MDR-ABC transporters may significantly improve further drug development and clinical treatment options