1,720,987 research outputs found
Role of the major toxic components from Vipera ammodytes venom in its immunogenicity with special emphasis on hemorrhagic metalloproteinases
Full text linkOtrov poskoka (Vipera a. ammodytes) se koristi u proizvodnji protuotrova protiv ugriza europskih zmija otrovnica. O strukturnim i funkcionalnim osobitostima njegovih glavnih toksičnih komponenti, amoditoksina (Atx-a) i hemoragina, postoje brojni literaturni podaci. Međutim, njihova imunogenost, tj. uloga u stvaranju zaštitnih antitijela sposobnih neutralizirati toksične učinke otrova, nije poznata. Stoga je cilj istraživanja bio pripremiti serume definirane specifičnosti imunizacijom kunića s pročišćenim komponentama – Atx-om A, ukupnom hemoraginskom frakcijom, odnosno kombinacijom Atx-a i hemoragina kako bi ispitali njihov zaštitni doprinos u neutralizaciji letalne toksičnosti inducirane cijelim otrovom. Prema rezultatima primijenjenog ED50 testa, jedine regulatorno priznate metode za procjenu potencije protuotrova protiv ugriza europskih zmija otrovnica, potpuno funkcionalna anti-Atx antitijela iskazuju iznimno slabu zaštitnu moć, dok ona specifična za ukupnu hemoraginsku frakciju uopće ne osiguravaju protekciju, iako su u životinjskom pokusnom modelu sama po sebi dostatna za neutralizaciju lokalnog hemoragičnog učinka. U kontekstu hemoragičnog efekta kao dominantne kliničke manifestacije otrovanja u ljudi za koju su zaslužne Zn2+-ovisne metaloproteinaze, cilj rada bio je i sustavno istražiti strukturu i funkciju potpuno novog reprezentativnog predstavnika skupine nazvanog amoditagin. Na njegovom primjeru je ispitan i doprinos antitijela specifičnih za jedan izdvojeni protein hemoragičnog fenotipa u neutralizaciji ukupne hemoragičnosti eksprimirane od strane otrova poskoka. Amoditagin je glikozilirani, blago kiseli heterodimer od 108 kDa s multidomenskom organizacijom jedinstvenom za pripadnike P-IIIc podgrupe koji je okarakteriziran kao enzim široke proteolitičke specifičnosti. Novoizolirani protein djeluje i kao jaki hemoragin. Prema rezultatima proizašlima iz ispitivanja njegove supstratne specifičnosti, hemoragičnost amoditagina najvjerojatnije je povezana s proteolitičkim efektom kojeg iskazuje na pojedine komponente bazalne membrane te faktore zgrušavanja krvi. Serum specifičan za amoditagin se pokazao dostatnim za neutralizaciju hemoragične aktivnosti cijelog otrova, što sugerira da bi indukcija nastanka anti-amoditagin antitijela mogla predstavljati bitni čimbenik u dobivanju terapeutski djelotvornog protuotrova.The venom of horn-nosed viper (Vipera a. ammodytes) has been used as an antigen for the production of antivenom against European vipers. In contrast to the detailed knowledge on structural and functional properties of ammodytoxins and hemorrhagins as its main toxic components, almost nothing has been known about their immunogenicity. Our research goal was to prepare the rabbit antisera containing antibodies specific for both classes of the pathology-inducing venom constituents and to evaluate the involvement of the obtained antibodies in neutralisation of the whole venom toxicity in mice. According to ED50 test, the only regulatory approved assay for the estimation of antivenom potency, fully functional antibodies specific for ammodytoxins participate in neutralisation of the whole venom's lethal toxicity only partially. Antibodies specific for hemorrhagins are not protective at all, despite their sufficiency in neutralisation of the local hemorrhagic effect in vivo. Furthermore, since hemorrhage as the prevalent clinical manifestation of envenoming in human is due to action of Zn2+-dependent metalloproteinases, structural and functional characterisation of the group representative, named ammodytagin, was of special research interest. Also, role of antibodies specific for individual protein exhibiting hemorrhagic phenotype in neutralisation of the whole venom hemorrhagicity was defined. Ammodytagin is a glycosylated, slightly acidic heterodimer of 108 kDa with multidomain organisation unique for members of P-IIIc subgroup which is characterised as enzyme of broad proteolytic specificity. The novel protein also acts as a strong hemorrhagin. Investigation of a substrate specificity revealed that hemorrhagic activity of ammodytagin might be the result of its involvement in cleavage of basal membrane components and depletion of coagulation factors in blood circulation. Finally, antiserum raised against ammodytagin was able to completely neutralise the hemorrhagic activity of the whole venom, suggesting it might be one of the key molecules towards which effective antivenom should be directed
Purification and properties of mumps and measles virus
Full text linkVirusi zaušnjaka (MuV) i ospica (MeV) uzrokuju istoimene bolesti u ljudi koje se mogu spriječiti cijepljenjem, a dobivaju na značaju i u onkolitičkoj viroterapiji. Cjelovitost i čistoća virusnih čestica osiguravaju učinkovitost i sigurnost ovakvih proizvoda, stoga je njihovo pročišćavanje i koncentriranje izuzetno važno u biotehnologiji, ali i temeljnim istraživanjima. Ciljevi ovog rada su ispitati pročišćavanje MuV-a i MeV-a kromatografijom hidrofobnih interakcija (HIC) i ionske izmjene (IEX), imunoafinitetnom kromatografijom (IAC), ultracentrifugiranjem (UC) i dijafiltracijom (DF), ispitati stabilnost virusa u uvjetima pročišćavanja i čuvanja te istražiti njihove lipidome i proteome. Rezultati pokazuju da IEX nije prikladan za pročišćavanje MuV-a i MeV-a, dok HIC i IAC daju relativno visoke prinose infektivnih virusa (60-70%). Na kromatografske prinose značajno utječe promjenjiva heterogenost početnih virusnih uzoraka. Analiza proteoma virusa potvrdila je prisutnost svih strukturnih virusnih proteina te staničnih proteina aktina, aneksina, ciklofilina A, integrina β1 i moezina, a njihov značaj u virionima tek treba utvrditi.Mumps (MuV) and measles (MeV) virus cause mumps and measles in humans, both preventable by vaccination, but they are gaining importance in oncolytic virotherapy. Viral particle integrity and purity ensure efficacy and safety of such products, therefore their purification and concentration is exceptionally important both in biotechnology and basic research. The aims of this work are to investigate purification of MuV and MeV by hydrophobic interaction (HIC), ion-exchange (IEX) and immunoaffinity chromatography (IAC), ultracentrifugation (UC) and diafiltration (DF), investigate virus stability under used purification and storage conditions and investigate their lipidomes and proteomes. Results deem IEX unsuitable for MuV and MeV purification, while HIC and IAC yield relatively high recoveries of infective viruses (60-70%). Chromatographic yields are significantly influenced by initial virus sample heterogeneity. Analysis of virus proteomes confirmed the presence of all structural viral proteins and cellular proteins actin, annexins, cyclophilin A, integrin β1 and moesin, but their significance in virions remains to be determined
Oncolytic virotherapy: Harnessing viruses for cancer treatment
Full text linkOnkolitička viroterapija (OVT) predstavlja inovativan oblik imunoterapije u kojem se za selektivnu destrukciju tumorskih stanica i poticanje antitumorskog imunosnog odgovora koriste virusi sa sposobnošću replikacije. Povijesno je uočeno da virusne infekcije mogu uzrokovati regresiju maligniteta, a suvremeni napredak u molekularnoj virologiji i genetskom inženjerstvu omogućio je razvoj sigurnijih i učinkovitijih onkolitičkih virusa. Danas su u kliničkoj primjeni odobrena tek četiri pripravka (Rigvir, Oncorine, T-VEC i Delytact), dok brojni drugi pokazuju obećavajuće rezultate u ispitivanjima. Translacija OVT-a u rutinsku praksu suočava se s izazovima, uključujući zahtjevnu proizvodnju, nedostatak prediktivnih pretkliničkih modela i ograničenu učinkovitost u terminalno oboljelih bolesnika. Prikaz uspješnog slučaja eksperimentalnog samoliječenja recidiva raka dojke u Hrvatskoj intratumorskom aplikacijom virusa ospica i virusa vezikularnog stomatitisa ukazuje na potencijal primjene ovakvih pristupa u nižim dozama i s jednostavnije pripremljenim pripravcima. Taj slučaj otvara nove hipoteze o optimizaciji terapije, a posebno naglašava važnost hrvatskog Edmonston Zagreb soja virusa ospica kao potencijalne platforme za razvoj domaće onkolitičke terapije. Zaključno, OVT je još uvijek eksperimentalna, ali iznimno perspektivna terapija koja bi, uz prilagodbu regulatornih okvira i ulaganje u istraživanje, mogla postati značajan doprinos liječenju malignih bolesti.Oncolytic virotherapy (OVT) is an innovative form of immunotherapy that employs replicationcompetent viruses for the selective destruction of tumor cells and the induction of antitumor immune responses. Historically, viral infections were observed to induce tumor regression, and modern advances in molecular virology and genetic engineering have enabled the development of safer and more effective oncolytic viruses. To date, only four preparations (Rigvir, Oncorine, T-VEC, and Delytact) have been approved for clinical use, while many others show promising results in trials. The translation of OVT into routine practice faces several challenges, including demanding production processes, the lack of predictive preclinical models, and limited efficacy in terminal-stage patients. A recent case of successful experimental self-treatment of recurrent breast cancer in Croatia, using intratumoral application of measles virus and vesicular stomatitis virus, highlights the potential of lower-dose and more simply prepared formulations. This case opens new hypotheses for therapy optimization and emphasizes the importance of the Croatian Edmonston Zagreb measles virus strain as a promising platform for the development of domestic oncolytic therapies. In conclusion, OVT remains experimental but highly promising, and with adapted regulatory frameworks and increased investment in research, it may become an important contribution to cancer treatment
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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