1,721,041 research outputs found

    Characterisation of cell membrane interaction mechanisms of antimicrobial peptides by electrical bilayer recording

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    Many antimicrobial peptides (AMPs) are cationic host defence peptides (HDPs) that interact with microbial membranes. This ability may lead to implementation of AMPs as therapeutics to overcome the wide-spread antibiotic resistance problem as the affected bacteria may not be able to recover from membrane lysis types of attack. AMP interactions with lipid bilayer membranes are typically explained through three mechanisms, i.e., barrel-stave pore, toroidal pore and carpet models. Electrical bilayer recording is a relatively simple and sensitive technique that is able to capture the nanoscale perturbations caused by the AMPs in the bilayer membranes. Molecular-level understanding of the behaviour of AMPs in relation to lipid bilayers mimicking bacterial and human cell membranes is essential for their development as novel therapeutic agents that are capable of targeted action against disease causing micro-organisms. The effects of four AMPs (aurein 1.2, caerin 1.1, citropin 1.1 and maculatin 1.1 from the skin secretions of Australian tree frogs) and the toxin melittin (found in the venom of honeybees) on two different phospholipid membranes were studied using the electrical bilayer recording technique. Bilayers composed of zwitterionic (DPhPC) and anionic (DPhPC/POPG) lipids were used to mimic the charge of eukaryotic and prokaryotic cell membranes, respectively, so as to determine the corresponding interaction mechanisms for different concentrations of the peptide. Analysis of the dataset corresponding to the four frog AMPs, as well as the resulting dataset corresponding to the bee toxin, confirms the proposed peptide-bilayer interaction models in existing publications and demonstrates the importance of using appropriate bilayer compositions and peptide concentrations for AMP studies

    Dizajn i karakterizacija nanočestica zlata i selena kao potencijanih sustava za dostavu levodope i dopamina

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    The development of new approaches in the treatment of Parkinson's disease presents a challenge due to the presence of the blood-brain barrier, which hinders effective drug delivery to the brain. Due to their unique physicochemical properties, nanoparticles have the potential to improve conventional therapeutic approaches and enable targeted drug delivery across the blood-brain barrier. The main goal of this doctoral thesis was to synthesize and characterize differently functionalized gold and selenium nanoparticles and to examine their interaction with catechols (levodopa and dopamine) in order to design more effective and safer therapeutic systems for Parkinson's disease. The process of drug binding to the nano-surface was investigated using various spectroscopic, laser and microscopic methods, while the bloodbrain barrier permeability of prepared nano-systems was tested under in vitro settings. The obtained results have provided a better understanding of the processes that occur during the binding of catechol drugs to gold and selenium nanoparticles. This will potentially enable the development of a nano-formulation with targeted drug delivery to the brain with the aim of improving the therapy of Parkinson's disease.Razvoj novih pristupa u liječenju Parkinsonove bolesti predstavlja izazov zbog prisutnosti krvno-moždane barijere koja otežava učinkovitu dostavu lijekova u mozak. Zahvaljujući jedinstvenim fizikalno-kemijskim svojstvima, nanočestice imaju potencijal poboljšati konvencionalne terapijske pristupe i omogućiti ciljanu isporuku lijekova preko krvnomoždane barijere. Glavni cilj ovog doktorskog rada bio je sintetizirati i karakterizirati različito funkcionalizirane nanočestice zlata i selena te ispitati njihovo međudjelovanje s kateholima (levodopa i dopamin) u svrhu dizajniranja učinkovitijih i sigurnijih terapijskih sustava za liječenje Parkinsonove bolesti. Proces vezanja lijekova na nano-površinu ispitivao se pomoću različitih spektroskopskih, laserskih i mikroskopskih metoda, a zatim su se provela istraživanja propusnosti krvno-moždane barijere za novopripravljene nanosustave u in vitro uvjetima. Dobiveni rezultati omogućili su bolje razumijevanje procesa koji se događaju prilikom vezanja lijekova kateholne strukture i novih nanočestica zlata i selena. Na taj način potiče se razvoj nano-formulacija s ciljanom isporukom lijekova u mozak s ciljem poboljšanja terapije za Parkinsonovu bolest

    Solid-state NMR studies of peripherally membrane-associated proteins: dealing with dynamics, disorder and dilute conditions

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    This chapter reviews applications of solid-state NMR to three peripheral membrane proteins: cardiolipin-bound cytochrome c, phosphatidylinositol-binding Pleckstrin homology domain and membrane-associated myelin basic protein. We describe solutions to common challenges, such as the dynamics of the membrane-bound protein and the preparation of suitable samples with biological relevance. Modern NMR hardware, molecular biology and sample preparation methods pave the way for effective studies of many interesting peripheral membrane proteins by solid-state NMR

    Dizajn i karakterizacija nanočestica zlata i selena kao potencijanih sustava za dostavu levodope i dopamina

    No full text
    The development of new approaches in the treatment of Parkinson's disease presents a challenge due to the presence of the blood-brain barrier, which hinders effective drug delivery to the brain. Due to their unique physicochemical properties, nanoparticles have the potential to improve conventional therapeutic approaches and enable targeted drug delivery across the blood-brain barrier. The main goal of this doctoral thesis was to synthesize and characterize differently functionalized gold and selenium nanoparticles and to examine their interaction with catechols (levodopa and dopamine) in order to design more effective and safer therapeutic systems for Parkinson's disease. The process of drug binding to the nano-surface was investigated using various spectroscopic, laser and microscopic methods, while the bloodbrain barrier permeability of prepared nano-systems was tested under in vitro settings. The obtained results have provided a better understanding of the processes that occur during the binding of catechol drugs to gold and selenium nanoparticles. This will potentially enable the development of a nano-formulation with targeted drug delivery to the brain with the aim of improving the therapy of Parkinson's disease.Razvoj novih pristupa u liječenju Parkinsonove bolesti predstavlja izazov zbog prisutnosti krvno-moždane barijere koja otežava učinkovitu dostavu lijekova u mozak. Zahvaljujući jedinstvenim fizikalno-kemijskim svojstvima, nanočestice imaju potencijal poboljšati konvencionalne terapijske pristupe i omogućiti ciljanu isporuku lijekova preko krvnomoždane barijere. Glavni cilj ovog doktorskog rada bio je sintetizirati i karakterizirati različito funkcionalizirane nanočestice zlata i selena te ispitati njihovo međudjelovanje s kateholima (levodopa i dopamin) u svrhu dizajniranja učinkovitijih i sigurnijih terapijskih sustava za liječenje Parkinsonove bolesti. Proces vezanja lijekova na nano-površinu ispitivao se pomoću različitih spektroskopskih, laserskih i mikroskopskih metoda, a zatim su se provela istraživanja propusnosti krvno-moždane barijere za novopripravljene nanosustave u in vitro uvjetima. Dobiveni rezultati omogućili su bolje razumijevanje procesa koji se događaju prilikom vezanja lijekova kateholne strukture i novih nanočestica zlata i selena. Na taj način potiče se razvoj nano-formulacija s ciljanom isporukom lijekova u mozak s ciljem poboljšanja terapije za Parkinsonovu bolest

    Dizajn i karakterizacija nanočestica zlata i selena kao potencijanih sustava za dostavu levodope i dopamina

    No full text
    The development of new approaches in the treatment of Parkinson's disease presents a challenge due to the presence of the blood-brain barrier, which hinders effective drug delivery to the brain. Due to their unique physicochemical properties, nanoparticles have the potential to improve conventional therapeutic approaches and enable targeted drug delivery across the blood-brain barrier. The main goal of this doctoral thesis was to synthesize and characterize differently functionalized gold and selenium nanoparticles and to examine their interaction with catechols (levodopa and dopamine) in order to design more effective and safer therapeutic systems for Parkinson's disease. The process of drug binding to the nano-surface was investigated using various spectroscopic, laser and microscopic methods, while the bloodbrain barrier permeability of prepared nano-systems was tested under in vitro settings. The obtained results have provided a better understanding of the processes that occur during the binding of catechol drugs to gold and selenium nanoparticles. This will potentially enable the development of a nano-formulation with targeted drug delivery to the brain with the aim of improving the therapy of Parkinson's disease.Razvoj novih pristupa u liječenju Parkinsonove bolesti predstavlja izazov zbog prisutnosti krvno-moždane barijere koja otežava učinkovitu dostavu lijekova u mozak. Zahvaljujući jedinstvenim fizikalno-kemijskim svojstvima, nanočestice imaju potencijal poboljšati konvencionalne terapijske pristupe i omogućiti ciljanu isporuku lijekova preko krvnomoždane barijere. Glavni cilj ovog doktorskog rada bio je sintetizirati i karakterizirati različito funkcionalizirane nanočestice zlata i selena te ispitati njihovo međudjelovanje s kateholima (levodopa i dopamin) u svrhu dizajniranja učinkovitijih i sigurnijih terapijskih sustava za liječenje Parkinsonove bolesti. Proces vezanja lijekova na nano-površinu ispitivao se pomoću različitih spektroskopskih, laserskih i mikroskopskih metoda, a zatim su se provela istraživanja propusnosti krvno-moždane barijere za novopripravljene nanosustave u in vitro uvjetima. Dobiveni rezultati omogućili su bolje razumijevanje procesa koji se događaju prilikom vezanja lijekova kateholne strukture i novih nanočestica zlata i selena. Na taj način potiče se razvoj nano-formulacija s ciljanom isporukom lijekova u mozak s ciljem poboljšanja terapije za Parkinsonovu bolest

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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