29 results on '"Živković, Martina"'
Search Results
2. Specific inhibition of fibroblast growth factor receptor 1 signaling by a DNA aptamer
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Zlinska, Vladimira, Feketova, Zuzana, Czyrek, Aleksandra, Chudzian, Julia, Zivkovic, Martina Lenarcic, Ursachi, Vlad-Constantin, Dudeja, Pooja, Fafilek, Bohumil, Rynes, Jan, Rico-Llanos, Gustavo, Koudelka, Adolf, Roy, Tanaya, Biadun, Martyna, Raskova, Vendula, Svozilova, Katerina, Stroblova, Michaela, Krzyscik, Mateusz, Hristova, Kalina, Krowarsch, Daniel, Foldynova-Trantirkova, Silvie, Zakrzewska, Malgorzata, Trantirek, Lukas, and Krejci, Pavel
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- 2025
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3. A sodium/potassium switch for G4-prone G/C-rich sequences
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Luo, Yu, primary, Živković, Martina Lenarčič, additional, Wang, Jiawei, additional, Ryneš, Jan, additional, Foldynová-Trantírková, Silvie, additional, Trantírek, Lukáš, additional, Verga, Daniela, additional, and Mergny, Jean-Louis, additional
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- 2023
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4. DNA i-motif levels are overwhelmingly depleted in living human cells: insights from in-cell NMR
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Víšková, Pavlína, primary, Ištvánková, Eva, additional, Ryneš, Jan, additional, Džatko, Šimon, additional, Loja, Tomáš, additional, Živković, Martina Lenarčič, additional, Rigo, Riccardo, additional, El-Khoury, Roberto, additional, Serrano-Chacón, Israel, additional, Damha, Masad J., additional, González, Carlos, additional, Mergny, Jean-Louis, additional, Foldynová-Trantírková, Silvie, additional, and Trantírek, Lukáš, additional
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- 2023
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5. A sodium/potassium switch for G4-prone G/C-rich sequences.
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Luo, Yu, Živković, Martina Lenarčič, Wang, Jiawei, Ryneš, Jan, Foldynová-Trantírková, Silvie, Trantírek, Lukáš, Verga, Daniela, and Mergny, Jean-Louis
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- 2024
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6. Post-translational S-Nitrosylation Is an Endogenous Factor Fine Tuning the Properties of Human S100A1 Protein
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Lenarčič Živković, Martina, Zaręba-Kozioł, Monika, Zhukova, Liliya, Poznański, Jarosław, Zhukov, Igor, and Wysłouch-Cieszyńska, Aleksandra
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- 2012
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7. Helicobacter pylori in pathogenesis of gastric malignant neoplasms
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Živković, Martina, Škrtić, Anita, Gašparov, Slavko, and Batelja-Vuletić, Lovorka
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Helicobacter pylori ,primary gastric lymphoma ,chronic gastritis ,gastric carcinoma - Abstract
Helicobacter pylori (HP) je gram negativna mikroaerofilna bakterija koja kolonizira sluznicu želuca. Opstanak u nepovoljnim uvjetima kisele sredine želuca omogućuje joj sinteza ureaze koja katalizira proizvodnju amonijaka i ugljikova dioksida iz uree i neutralizira želučani pH. Kolonizacijom je zahvaćena približno polovica svjetske populacije, s većom prevalencijom u državama u razvoju, zbog čega se dovodi u vezu sa socioekonomskim statusom. U većini slučajeva kolonizacija dovodi do asimptomatske infekcije. Dugotrajna infekcija uzrokovana HP može rezultirati razvojem kroničnog gastritisa. Kronični atrofični gastritis čini prvi korak Correa kaskade koja predstavlja postepenu progresiju promjena na želučanoj sluznici koje vode nastanku karcinoma želuca. Navedene promjene uključuju atrofiju žljezdanog epitela, intestinalnu metaplaziju epitela i displaziju epitela. U patogenezi karcinoma želuca, osim bakterijskih faktora virulencije, važnu ulogu imaju osobine domaćina te okolišni čimbenici. Karcinom želuca je peti najčešći tumor u svijetu. Zbog odsutnosti kliničkih simptoma i posljedično kasne dijagnoze, karcinom želuca karakterizira visoka stopa mortaliteta. Probavni sustav je najčešće primarno sijelo ekstranodalnog non-Hodgkinovog limfoma. U otprilike dvije trećine slučajeva riječ je o želucu. HP infekcija predstavlja jedan od glavnih rizičnih čimbenika za razvoj primarnih limfoma želuca (PGL). Upalna reakcija posredovana HP inducira proliferaciju B-limfocita i stvaranje limfnih folikula unutar želučane sluznice. Tijekom vremena zbog nakupljenih genetskih promjena dolazi do autonomnog rasta klona B-stanica i nastanka limfoma. Eradikacija infekcije u velikog broja pacijenata smanjuje rizik za pojavu premalignih lezija, i čak vodi regresiji ranih stadija limfoma. Endoskopija i patohistološka dijagnoza predstavljaju standardni postupak u otkrivanju neoplazmi želuca., Helicobacter pylori (HP) is a gram negative microaerobic bacterium that colonizes the gastric mucosa. Survival in adverse conditions of acidic gastric medium is enabled by urease synthesis, which catalyses production of ammonia and carbon dioxide from urea and neutralizes gastric pH. Colonization affects nearly half of the global population, with higher prevalence in developing countries, which is why it is related to socioeconomic status. In most cases colonization leads to asymptomatic infection. Long-term infection by HP may result in the development of chronic gastritis. The chronic atrophic gastritis makes the first step in Correa´s cascade, which represents a gradual progression of gastric mucosal changes that lead to the development of gastric carcinoma. That changes include glandular atrophy, intestinal metaplasia and dysplasia of the epitelium. Besides bacterial virulence factors, host properties and environmental factors play an important role in the pathogenesis of gastric carcinoma. Gastric carcinoma is the fifth most common cancer worldwide. Because of clinical symptom absence, and consequently late diagnosis, gastric carcinoma is characterized by high mortality rate. The digestive system is the most common primary site of extranodal non-Hodgkin lymphomas. The stomach makes approximately two-thirds of cases. HP infection represents one of the main risk factors for primary gastric lymphoma (PGL) development. Inflammatory reaction mediated by HP induces B-cell proliferation and lymphoid follicle formation within gastric mucosa. Over time, because of accumulated genetic changes, autonomous growth of B-cell clone occurs and lymphoma develops. In a large number of patients, infection eradication decreases risk for premalignant lesion appearance, and even leads to early stage MALT lymphoma regression. Endoscopy and pathohistological diagnosis present standard procedure in gastric neoplasm finding.
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- 2021
8. Insight into formation propensity of pseudocircular DNA G-hairpins
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Živković, Martina Lenarčič, primary, Gajarský, Martin, additional, Beková, Kateřina, additional, Stadlbauer, Petr, additional, Vicherek, Lukáš, additional, Petrová, Magdalena, additional, Fiala, Radovan, additional, Rosenberg, Ivan, additional, Šponer, Jiří, additional, Plavec, Janez, additional, and Trantírek, Lukáš, additional
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- 2021
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9. Structure of a DNA G-Quadruplex Related to Osteoporosis with a G-A Bulge Forming a Pseudo-loop
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Lenarčič Živković, Martina, primary, Rozman, Jan, additional, and Plavec, Janez, additional
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- 2020
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10. Kvalitativni pristup procjeni rizika u autonomnoj navigaciji
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Živković, Martina
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autonomni pomorski sustav, procjena rizika, autonomna navigacija, navigacijski sustavi, senzori, razine autonomije, autonomni brod, Bayesova mreža - Abstract
Očekivane prednosti autonomnih pomorskih sustava u usporedbi s konvencionalnim pomorskim sustavima su smanjeni operativni troškovi, manji rizik za operatere i povećana učinkovitost takvih sustava. Teško je procijeniti rizik novih tehnoloških sustava radi nepostojanja iskustva s tim sustavima i stoga nisu dostupni podaci za evaluaciju. Tri izazova u vezi s procjenom rizika složenih autonomnih pomorskih sustava su uključivanje softvera u procjenu rizika tehnoloških sustava, procjena uloge ljudskih operatera koji će nadzirati autonomne pomorske sustave i intervenirati ako je potrebno te dinamičnost morskog okoliša, odnosno vrijeme i stanje mora, koje je stalno promjenjivo. U radu je predstavljena Bayesova mreža kako bi se procijenila učinkovitost suradnje između čovjeka i autonomije, kao dio modela rizika za rad podvodnih autonomnih vozila. Preko Bayesove mreže prikazana je i procjena rizika u autonomnoj navigaciji s aspekta sigurnosti. Na kraju je preko modela prikazana procjena rizika za današnje brodove i brodove koji su autonomni s mogućnošću daljinskog upravljanja kako bi se vidjela razlika u upravljanju. Na današnjim brodovima upravljanje vrši posada na brodu, dok rad autonomnog broda nadzire operater daljinski s obale.
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- 2019
11. Innentitelbild: Adenine‐Driven Structural Switch from a Two‐ to Three‐Quartet DNA G‐Quadruplex (Angew. Chem. 47/2018)
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Lenarčič Živković, Martina, primary, Rozman, Jan, additional, and Plavec, Janez, additional
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- 2018
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12. Adenine‐Driven Structural Switch from a Two‐ to Three‐Quartet DNA G‐Quadruplex
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Lenarčič Živković, Martina, primary, Rozman, Jan, additional, and Plavec, Janez, additional
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- 2018
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13. Inside Cover: Adenine‐Driven Structural Switch from a Two‐ to Three‐Quartet DNA G‐Quadruplex (Angew. Chem. Int. Ed. 47/2018)
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Lenarčič Živković, Martina, primary, Rozman, Jan, additional, and Plavec, Janez, additional
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- 2018
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14. 19F NMR studies provide insights into lipid membrane interactions of listeriolysin O, a pore forming toxin from Listeria monocytogenes
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Kozorog, Mirijam, primary, Sani, Marc-Antoine, additional, Lenarčič Živković, Martina, additional, Ilc, Gregor, additional, Hodnik, Vesna, additional, Separovic, Frances, additional, Plavec, Janez, additional, and Anderluh, Gregor, additional
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- 2018
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15. Turbo-napojna pumpa
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Živković, Martina and Orović, Josip
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construction ,condensate system ,turbo-napojna pumpa ,Coffin ,TECHNICAL SCIENCES. Traffic and Transport Technology. Maritime and River Traffic ,sustav kondenzata ,Shinko ,TEHNIČKE ZNANOSTI. Tehnologija prometa i transport. Pomorski i riječni promet ,konstrukcijske izvedbe ,feed water system ,feed water turbo-pump ,sustav napojne vode - Abstract
U radu je prikazan sustav napojne vode od otplinjača, preko napojnih pumpi do generatora pare te priprema istog za normalan rad. Također prikazane su dvije najčešće korištene turbo-napojne pumpe, Coffin i Shinko. U radu su opisane konstruktivne izvedbe ovih pumpi i procedura prilikom pripreme i pokretanja ovih pumpi. Na kraju rada je prikazan proračun aksijalne turbine. Korišteni su poznati podatci sa jednog LNG broda i na temelju poznatih parametara tlaka i temperature ulazne pare izračunate su iskoristivost, snaga turbine, brzine pare kroz turbinu i drugi parametri. In this paper, feed water is circulating from thr deaerator, via the feed pumps to the boiler and preparation for operation. There are two different types of turbo-feed pumps, Coffin and Shinko. Construction of the pumps and their procedure to prepare them for starting are described in this paper. At the end of the paper axial turbine is shown. Characteristics from one LNG ship are used. Based on the known parameters of pressure and temperature of inlet steam, efficiency, power turbine, speed of steam through a turbine and other parameters are calculated.
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- 2016
16. Non-canonical Structures in Promoter Modulate Gene Expression in Escherichia coli
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Božič Abram, Sabina, primary, Marušič, Maja, additional, Lenarčič Živković, Martina, additional, Brčić, Jasna, additional, and Plavec, Janez, additional
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- 2018
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17. Structure of a Stable G-Hairpin
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Gajarský, Martin, primary, Živković, Martina Lenarčič, additional, Stadlbauer, Petr, additional, Pagano, Bruno, additional, Fiala, Radovan, additional, Amato, Jussara, additional, Tomáška, L’ubomír, additional, Šponer, Jiří, additional, Plavec, Janez, additional, and Trantírek, Lukáš, additional
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- 2017
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18. DJEČJA GLAZBENA KREATIVNOST U RANOM I PREDŠKOLSKOM ODGOJU I OBRAZOVANJU
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Živković, Martina
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dječja kreativnost ,dječje glazbeno stvaralaštvo ,glazbena nadarenost ,glazbene sposobnosti - Abstract
Glazbeni odgoj u predškolskoj ustanovi, kao i u roditeljskom domu, iznimno je bitan za poticanje dječje kreativnosti, a samim time utječe i na psihički i fizički razvoj djeteta. U nastojanju da se što bolje objasni pojam glazbene kreativnosti kod djece rane i predškolske dobi, u ovom radu je objašnjen prije svega pojam kreativnosti općenito, kao i pojam odnosno važnost divergentnog mišljenja i kako se aktivira desna moždana hemisfera te koja je njena uloga u kreativnom razmišljanju i ponašanju djeteta. Također je objašnjen i razvoj kreativnosti kod djece rane i predškolske dobi. Naglasak se stavlja na razvoj glazbenih sposobnosti djece. Uz to, objašnjen je pojam glazbene nadarenosti te znakovi za rano otkrivanje i razvoj nadarenosti. U razvijanju glazbene sposobnosti i nadarenosti veliku ulogu ima odgojitelj, koji je ključan i kompetentan u radu s djecom. On na razne načine potiče razvoj glazbenih sposobnosti i potiče dječje glazbeno stvaralaštvo. Navode se i konkretni primjeri brojnih aktivnosti za razvoj glazbene kreativnosti kod djece predškolske dobi vezanih za pjevanje, slušanje, glazbene igre i sviranje na udaraljkama.
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- 2015
19. Utjecaj gnojidbe i obrade tla na zarazu zrna pšenice Fusarium vrstama
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Živković, Martina, Ćosić, Jasenka, Vrandečić, Karolina, and Jug, Danijel
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chiseling ,disk harowing ,no-till ,fertilization ,wheat ,conventional tillage ,subsoiling ,pšenica ,gnojidba ,konvencionalna obrada ,rahljenje ,tanjuranje ,podrivanje ,izostavljena obrada - Abstract
Cilj ovog istraživanja bio je utvrditi pojavu Fusarium vrsta na zrnu pšenice pri različitim varijantama obrade tla i gnojidbe tijekom 2013./2014. godine. Pokus je postavljen na lokalitetu Čačinci u 5 varijanti obrade tla i 3 varijante gnojidbe dušikom. Utvrdili smo prisustvo vrsta iz roda Fusarium na zrnu pšenice u svim ispitivanim varijantama obrade tla i gnojidbe. Pri gnojidbi dušikom u preporučenoj i višoj dozi zaraza zrna fuzariozama je bila statistički značajno veća nego u tretmanima sa smanjenom gnojidbom u različitim obradama tla (konvencionalna obrada, podrivanje, no till). Pri smanjenoj gnojidbi dušikom najveći broj zaraženih zrna utvrđen u varijanti CH (rahljenje) i DH (tanjuranje), dok je najmanji broj zaraženih zrna utvrđen u konvencionalnoj obradi tla (CT) i podrivanju (SS) te u izostavljenoj obradi tla (NT)., The aim of the study was to determine the occurrence of Fusarium species on wheat grain under different tillage and fertilization treatments during 2013/2014 season. The experiment was set up at Čačinci site with 5 tillage and 3 nitrogen fertilization treatments. The presence of Fusarium species was recorded on wheat grains in all tillage and fertilization treatments. Infection of wheat grains with Fusarium species was statistically higher in treatments with nitrogen fertilization at the recommended and higher rate than in treatments with lower fertilization rate in different tillage systems (conventional tillage, subsoiling, no till). In treatments with lower nitrogen fertilization the largest number of infected seeds was found in CH (chiseling) and DH (disk harowing) tillage systems, while the lowest number of infected seeds was determined in conventional tillage (CT), subsoiling (SS) and no-till (NT) treatments
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- 2015
20. Najznačajnije vrste kukaca iz podreda Adephaga (Coleoptera)
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Živković, Martina
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kornjaši ,prirodni neprijatelji ,vodeni kukci ,štetnik ,poljoprivreda - Abstract
Podred Adephaga pripada redu Coleoptera – kornjaši. Ima 9 porodica, a najznačajnije su Carabidae, Dytiscidae i Gyrinidae. Carabidae su najvažniji neprijatelji brojnih vrsta štetnika koji pričinjavaju štete u poljoprivredi. Važni su i u agroekosustavu zato što se hrane sjemenkama korovnih biljaka i time pridonose smanjenu korova. Najpoznatije vrste iz roda Carabus su: C. intricatus L., C. violaceus L., C. cancellatus L. koji je u Hrvatskoj dosta čest. Najpoznatije vrste iz roda Calosoma su: C. sycophanta L., C. investigator Illiger, C. inquisitor L. Zabrus tenebrioides je trčak koji pričinjava velike štete u poljoprivredi, jedna od rijetkih štetnih vrsta iz podreda Adephaga. Kornjaši koji najmanje jedan stadij životnog ciklusa provode u vodi nazivamo vodeni kukci. Najznačajniji rodovi su Hygrotus, Dytiscus s vrstom D. marginalis Linnaeus i Graphoderus s vrstom G. bilineatus De Geer.
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- 2013
21. Anaerobna digestija organske tvari
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Živković, Martina
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Anaerobna digestija ,Anaerobni reaktori ,Čimbenici anaerobne digestije - Abstract
Anaerobna digestija (AD) se smatra održivom opcijom za gospodarenje otpadnom biomasom zbog proizvodnje obnovljive energije i recikliranja nutrijenata. Općenito, anaerobna digestija obuhvaća hidrolizu, acidogenezu, acetogenezu i metanogenezu, a svaki metabolički stupanj je u funkciji aktivnosti mikroorganizama. Hidroliza je stupanj koji najviše ograničava brzinu procesa. Na proces anaerobne digestije utječu mnogi kemijski i fizikalni čimbenici poput ukupne količine krute tvari, ukupne količine hlapivih tvari, sadržaj ugljika i dušika i njihov omjer (C/N), temperatura, pH, tragovi metala. Anaerobna digestija je jedan od najviše obećavajućih procesa zbog energetske pretvorbe organskog otpada i očekuje se da će se početi koristiti na globalnoj razini zbog njegovog doprinosa okolišu i energetske učinkovitosti. Ko-digestija različitih vrsta biootpada je bila diskutirana u mnogim istraživačkim radovima, zbog njene mogućnosti povećanja proizvodnje bioplina i poboljšanja stabilnosti anaerobnog sustava.
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- 2012
22. STD NMR and molecular modelling insights into interaction of novel mannose-based ligands with DC-SIGN
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Kotar, Anita, primary, Tomašič, Tihomir, additional, Lenarčič Živković, Martina, additional, Jug, Gregor, additional, Plavec, Janez, additional, and Anderluh, Marko, additional
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- 2016
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23. Post-translational S-Nitrosylation Is an Endogenous Factor Fine Tuning the Properties of Human S100A1 Protein.
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Živković, Martina Lenarčič, Zaręba-Kozioł, Monika, Zhukova, Liliya, Poznański, Jaroslaw, Zhukov, Igor, and Wysłouch-Cieszyńska, Aleksandra
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NITROSYLATION , *HOMEOSTASIS , *NEUROTRANSMITTER receptors , *CELLULAR signal transduction , *ISOTHERMAL titration calorimetry , *CYSTEINE - Abstract
S100A1 is a member of the Ca2+-binding S100 protein family. It is expressed in brain and heart tissue, where it plays a crucial role as a modulator of Ca2+ homeostasis, energy metabolism, neurotransmitter release, and contractile performance. Biological effects of S100A1 have been attributed to its direct interaction with a variety of target proteins. The (patho)physiological relevance of S100A1 makes it an important molecular target for future therapeutic intervention. S-Nitrosylation is a post-translational modification of proteins, which plays a role in cellular signal transduction under physiological and pathological conditions. In this study, we confirmed that S100A1 protein is endogenously modified by Cys85 S-nitrosylation in PC12 cells, which are a well established model system for studying S100A1 function. We used isothermal calorimetry to show that S-nitrosylation facilitates the formation of Ca2+-loaded S100A1 at physiological ionic strength conditions. To establish the unique influence of the S-nitroso group, our study describes high resolution three-dimensional structures of human apo-S100A1 protein with the Cys85 thiol group in reduced and S-nitrosylated states. Solution structures of the proteins are based on NMR data obtained at physiological ionic strength. Comparative analysis shows that S-nitrosylation fine tunes the overall architecture of S100A1 protein. Although the typical S100 protein intersubunit four-helix bundle is conserved upon S-nitrosylation, the conformation of S100A1 protein is reorganized at the sites most important for target recognition (i.e. the C-terminal helix and the linker connecting two EF-hand domains). In summary, this study discloses cysteine S-nitrosylation as a new factor responsible for increasing functional diversity of S100A1 and helps explain the role of S100A1 as a Ca2+ signal transmitter sensitive to NO/redox equilibrium within cells. [ABSTRACT FROM AUTHOR]
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- 2012
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24. Non-canonical Structures in Promoter Modulate Gene Expression in Escherichia coli.
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Abram, Sabina Božič, Marušič, Maja, Živković, Martina Lenarčič, Brčić, Jasna, and Plavec, Janez
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GENE expression , *RNA polymerases , *ESCHERICHIA coli , *THERMAL stability , *CRYSTAL structure - Abstract
Herein we show how sequences that can form different non-canonical structures affect gene expression levels when inserted in the core of σ70-dependent promoter, between the -35 and -10 elements recognized by RNA polymerase, in E. coli. We note that influence on level of GFP expression varies considerably depending on introduction of non-canonical structural elements in the antisense and sense strands as well as with their propensities to form G-triplex, G-hairpin, hairpin or G-quadruplex structures. Moreover, the extent of repression of expression does not relate to the in vitro thermal stability in a simple manner. Repression is most likely caused by steric interference rather than improper distance between the -35 and -10 elements. Although properties like thermal stability and topology can be somewhat different under in vivo and in vitro conditions, our results suggest that the extent of expression suppression cannot be dependent solely on thermal stabilities of Grich structures alone. [ABSTRACT FROM AUTHOR]
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- 2018
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25. Structure of a Stable G-Hairpin
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Jussara Amato, Jiří Šponer, Lukáš Trantírek, Radovan Fiala, Petr Stadlbauer, Martin Gajarský, Bruno Pagano, Lubomir Tomaska, Janez Plavec, Martina Lenarčič Živković, Gajarský, Martin, Živković, Martina Lenarčič, Stadlbauer, Petr, Pagano, Bruno, Fiala, Radovan, Amato, Jussara, Tomáška, L'Ubomír, Šponer, Jiří, Plavec, Janez, and Trantírek, Lukáš
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0301 basic medicine ,Guanine ,Base pair ,Saccharomyces cerevisiae ,Oligonucleotides ,Stacking ,Atomic resolution structure, Oligonucleotides, DNA structure, Base pairing, Thermodynamics, Yeast, Telomeric DNA, NMR ,Antiparallel (biochemistry) ,Biochemistry ,Catalysis ,DNA sequencing ,03 medical and health sciences ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,biology ,Chemistry ,Oligonucleotide ,DNA ,General Chemistry ,Telomere ,biology.organism_classification ,Molecular biology ,Crystallography ,030104 developmental biology ,Nucleic Acid Conformation ,Sequence motif - Abstract
In this study, we report the first atomic resolution structure of a stable G-hairpin formed by a natively occurring DNA sequence. An 11-nt long G-rich DNA oligonucleotide, 5'-d(GTGTGGGTGTG)-3', corresponding to the most abundant sequence motif in irregular telomeric DNA from Saccharomyces cerevisiae (yeast), is demonstrated to adopt a novel type of mixed parallel/antiparallel fold-back DNA structure, which is stabilized by dynamic G:G base pairs that transit between N1-carbonyl symmetric and N1-carbonyl, N7-amino base-pairing arrangements. Although the studied sequence first appears to possess a low capacity for base pairing, it forms a thermodynamically stable structure with a rather complex topology that includes a chain reversal arrangement of the backbone in the center of the continuous G-tract and 3'-to-5' stacking of the terminal residues. The structure reveals previously unknown principles of the folding of G-rich oligonucleotides that could be applied to the prediction of natural and/or the design of artificial recognition DNA elements. The structure also demonstrates that the folding landscapes of short DNA single strands is much more complex than previously assumed.
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- 2017
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26. NMR studies of human prion protein mutants in solution
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Biljan, Ivana, Ilc, Gregor, Giachin, Gabriele, Legname, Giuseppe, Plavec, Janez, Vodiškar, Mateja, Podbevšek, Peter, Plavec, Janez, and Lenarčić Živković, Martina
- Subjects
animal diseases ,Prion protein ,Mutants ,NMR structure ,nervous system diseases - Abstract
Transmissible spongiform encephalopathies (TSEs) are a rare group of rapidly progressive, invariably fatal neurodegenerative diseases affecting humans and animals. A hallmark of TSEs is the conformational conversion of the physiological cellular prion protein, PrPC, into a disease-associated form known as prion or PrPSc. A major focus in prion biology is unraveling the molecular mechanism leading to the structural conversion of PrPC to its pathological form PrPSc. In our recent studies, we tried to understand the early events of the conformational changes leading to PrPSc using as investigative tools point mutations clustered in the open reading frame of the human PrP gene and linked to genetic forms of human prion diseases. We have determined high- resolution solution-state NMR structures of the truncated recombinant human (Hu) PrP (residues 90-231) with pathological Q212P and V210I mutations linked to Gerstmann-Sträussler- Scheinker (GSS) syndrome and genetic Creutzfeldt–Jakob disease (CJD), respectively. In addition, we examined the NMR structure of the recombinant HuPrP (residues 90-231) carrying naturally occurring E219K polymorphism considered to protect against sporadic CJD (sCJD). 3D structures of HuPrP(Q212P), HuPrP(V210I) and HuPrP(E219K) proteins share similar global architecture with the WT HuPrP consisting of highly flexible N-terminal tail and a well-structured C-terminal domain, the latter containing three alpha-helices and a short antiparallel beta-sheet. Detailed inspection revealed that pathological Q212P and V210I mutations introduce some local structural variations with respect to the WT HuPrP which are mostly clustered at the alpha2-alpha3 interhelical interface and in the beta2-alpha2 loop region. Alteration of conformation of the beta2-alpha2 loop region and subsequent higher exposure of hydrophobic residues to solvent may facilitate intermolecular interactions involved in spontaneous generation of PrPSc in genetic TSEs. On contrary to the HuPrP(Q212P) and HuPrP(V210I), the structure of HuPrP(E219K) does not point to interruption of aromatic and hydrophobic interactions in the beta2-alpha2 loop region. Noteworthy, it seems that the beta2-alpha2 loop in HuPrP(E219K) is somewhat better defined in comparison to the same region in the WT protein and proteins with pathological Q212P and V210I mutations. In addition to such subtle structural rearrangements localized within the epitopes critical for prion conversion, replacement of Glu219 by Lys induces significant alteration of surface charge distribution with respect to the WT protein what may further account for protective influence of E219K polymorphism against sCJD.
- Published
- 2012
27. NMR structural insights into effects of point mutations in Human genome on prion protein
- Author
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Ilc, G, Biljan, I, Giachin, G, Zhukov, I, Legname, Giuseppe, Plavec, J., Vodiškar, Mateja, Podbevšek, Peter, Plavec, Janez, and Lenarčič Živković, Martina
- Subjects
animal diseases ,Prions ,Mutants ,NMR structure ,nervous system diseases - Abstract
Transmissible spongiform encephalopathies (TSEs), or prion diseases, are invariably fatal neurodegenerative disorders affecting humans and animals. Human prion diseases include Creutzfeldt-Jakob disease (CJD), fatal familial insomnia (FFI), Gerstmann-Sträussler-Scheinker (GSS) syndrome, and kuru, whereas the most common prion diseases in animals are scrapie in sheep, bovine spongiform encephalopathy, and chronic wasting disease in cervids. Prions are thought to consist solely of a misfolded isoform (PrPSc) of the normal, host-encoded cellular protein (PrPC), whose function is still unknown. Human (Hu) PrPC is a 209 residues long glycoprotein, tethered to the outer leaflet of the plasma membrane by a glycosylphosphatidylinositol (GPI) anchoring and its primary structure is highly conserved among mammals. According to the „protein-only hypothesis”, during the course of prion diseases, PrPC is converted into the abnormal form by a conversion process whereby most alpha-helix motives are replaced by beta-sheet secondary structures. One of the strongest arguments supporting the „protein-only hypothesis” is the link between inherited prion diseases and mutations in the PRNP gene. Approximately 10-15 % of TSEs are associated with mutations. In our recent works, we have determined the NMR solution-state structures of the truncated recombinant human (Hu) PrPs carrying the pathological Q212P (90-231, M129) and V210I (90-231, M129) mutation. While Q212P mutation is linked Gerstmann-Sträussler-Scheinker syndrome (GSS) the V210I mutation is linked to genetic Creutzfeldt-Jakob disease (CJD). In order to determine high-resolution structures triple resonance (1H, 13C and 15N) NMR experiments were performed by 800 MHz NMR spectrometer. Detailed analysis and comparison with the structure of the WT Hu-PrP revealed that although structures share similar global fold, mutations introduces some local structural differences. The observed variations are mostly clustered at the alpha2-alpha3 inter-helical interface and in the beta2-alpha2 loop region. The alteration of conformation of the beta2–alpha2 loop region and the subsequent changes in hydrophobic cluster may facilitate intermolecular interactions between PrPs. The high-resolution NMR structures offer new clues on the earliest events of the pathogenic conversion process and could be used for the the development of antiprion drugs.
- Published
- 2012
28. Decoupling, Tuning, Matching and Cable Length Effects on NMR Noise Spectra
- Author
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Müller, Norbert, Schlagnitweit, Judith, Horničáková, Michaela, Nausner, Martin, Jerschow, Alexej, Bendet-Taicher, Eli, Desvaux, Hervé, Morgan, Steven W., Smrečki, Vilko, Vodiškar, Mateja, Podbevšek, Peter, Plavec, Janez, and Lenarčič Živković, Martina
- Subjects
Spin noise ,NMR noise spectra - Abstract
The complex tuning dependence of NMR noise spectra [1, 2] can be attributed largely to absorbed circuit noise (ACN), which exhibits a complex line shape, that depends on sample and probe properties. It is always superimposed by a purely absorptive spin noise contribution. Pure spin noise has been observed in wide line solid spectra [3] and in presence of static field gradients [4]. Previously, it was shown that a symmetrical dip line shape of a strong solvent noise signal can be used as a good indicator for tuning to optimum receiving conditions: the spin noise tuning optimum (SNTO) [2, 5]. We have investigated line shape changes of NMR noise signals upon systematic variation of the tuning and matching adjustments as well as cable lengths. It turns out that on most probes more than one SNTO-dip situation can be found. On many probes one finds that the conventional tuning optimum (CTO) and SNTO are far apart in tuning frequency. Reception sensitivity has been observed to be at a maximum at the SNTO. Using the systematic tuning-matching approach and varying cable lengths one can find conditions, where both pulse excitation and reception properties of a commercial NMR probe are at optimum values [6]. Under optimal conditions even recording of decoupled and coupled C-13 NMR noise spectra thus becomes feasible [7]. References: [1] Giraudeau P., Müller N., Jerschow A. and Frydman L., Chem. Phys. Lett., 489, 107-112 (2010) [2] Nausner M., Schlagnitweit J., Smrecki V., Yang X., Jerschow A. and Müller N., J. Magn. Reson., 198, 73-79 (2009) [3] Schlagnitweit J., Dumez J.-N., Nausner M., Jerschow A., Elena-Herrmann B. and Müller N., J. Magn. Reson., 207, 168-172 (2010) [4] Müller N. and Jerschow A., Proc. Natl. Acad. Sci. U.S.A., 103, 6790-6792 (2006) [5] Nausner M., Goger M., Bendet-Taicher E., Schlagnitweit J., Jerschow A. and Müller N., J. Biomol. NMR, 48, 157-167 (2010) [6] Bendet-Taicher E., Müller N. and Jerschow A., ArXiv, 2012arXiv:1209.5024B (2012) [7] Schlagnitweit J. and Müller N., J. Magn. Reson., 224, 78-81 (2012)
- Published
- 2012
29. 19 F NMR studies provide insights into lipid membrane interactions of listeriolysin O, a pore forming toxin from Listeria monocytogenes.
- Author
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Kozorog M, Sani MA, Lenarčič Živković M, Ilc G, Hodnik V, Separovic F, Plavec J, and Anderluh G
- Subjects
- Bacterial Toxins genetics, Bacterial Toxins metabolism, Cell Membrane metabolism, Heat-Shock Proteins genetics, Heat-Shock Proteins metabolism, Hemolysin Proteins genetics, Hemolysin Proteins metabolism, Membrane Lipids metabolism, Models, Molecular, Molecular Conformation, Mutation, Protein Binding, Structure-Activity Relationship, Bacterial Toxins chemistry, Cell Membrane chemistry, Fluorine-19 Magnetic Resonance Imaging, Heat-Shock Proteins chemistry, Hemolysin Proteins chemistry, Membrane Lipids chemistry
- Abstract
Listeria monocytogenes is a mammalian pathogen that causes gastroenteritis, miscarriages and infections of the central nervous system in immunocompromised individuals. Its main virulence factor is listeriolysin O (LLO), a pore-forming cholesterol-dependent cytolysin (CDC), which enables bacterial escape from the phagolysosome and contributes to bacterial pathogenicity. Details of cholesterol (Chol) recognition and membrane binding mechanisms by LLO are still not known. Here we used
19 F-NMR spectroscopy in order to assess LLO-Chol interactions in solution and in a Chol-rich membrane environment. LLO has six tryptophan residues located in the region of the molecule that is first in contact with lipid membranes.19 F-LLO, which contained 5-fluoro-tryptophans, was prepared by using isotopic labelling in an E. coli expression system. Signals in the19 F-NMR spectrum of19 F-LLO were unambiguously assigned by using a series of single Trp → Phe point mutations. The results employing various cholesterol preparations in solution indicate that tryptophan residues are not directly involved in Chol binding in solution. However, significant chemical shift changes were observed upon LLO binding to Chol-rich membranes, highlighting the role of tryptophan residues in membrane interactions (W512) and oligomerisation (W189 and W489).- Published
- 2018
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