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HSV-1 infekcija dovodi do redistribucije jezgrene ADAR1 p110 izoforme
No full textHerpes simplex virus 1 (HSV-1) is a dsDNA virus, which causes many different pathological conditions in the human population. The virus has the ability to modulate host immune response, which enables its replication. Adenosine deaminase acting on RNAs (ADAR) proteins are enzymes, whose main function is deamination of adenosine to inosine on dsRNA molecules, which consequently alters their structure and function. ADAR1 is the member of ADAR family, which is a known modulator of the immune response. Therefore, ADAR1 can exhibit proviral and antiviral effects, during viral infections. ADAR1 possesses two functionally active isoforms: p110 (constitutively expressed) and p150 (expression induced with the interferons (IFNs)). To add new insights to the HSV-1 field of research, we investigated whether ADAR1 proteins exhibit the ability to change their subcellular localisation during the early phase of HSV-1 productive infection. Firstly, by using the immunofluorescence and subcellular fractionation methods, we determined the ADAR1 expression profile of MOCK infected RPE1 cells. Results show that both p110 and p150 isoforms localise mainly in the nucleus of uninfected and unstimulated RPE1 cells. We also used immunofluorescence and subcellular fractionation to examine whether the translocation of ADAR1 proteins happens during first 24 hours after the infection. These results show that ADAR1 p110 isoform translocates from the nucleus to the cytoplasm, at a time point between 7 and 24 hours after infection. On the other hand, p150 isoform depletes in both the nucleus and the cytoplasm during the first day of the infection. Afterwards, we tried to compare cellular expression of ADAR1 isoforms between MOCK and HSV-1 infected RPE1 cells. Also, we analysed expression profile of ADAR1 proteins, during first 24 hours after infection, in several different cell lines. These data, together with the ADAR1 transcriptome analysis, show that the expression of ADAR1 proteins does not elevate during the early phase of HSV-1 productive infection. Nonetheless, increased expression of both ADAR1 isoforms, induced by the IFN-β, does not contribute to increased amounts of ADAR1 proteins in the cytoplasm. This was confirmed by the immunoflurescence and Western blot method. Overall, described results indicate that ADAR1 p110 translocates from the nucleus to the cytoplasm of RPE1 cells, and that this phenotype is not caused by the increase in protein's expression.Herpes simpleks virus 1 (HSV-1) je dvolančani DNA virus, koji uzrokuje više različitih patofizioloških stanja u ljudskoj populaciji. Virus ima sposobnost moduliranja imunosnog odgovora domaćina, što omogućuje njegovu replikaciju. Adenozin deaminaza koja djeluje na RNA (engl. Adenosine deaminase acting on RNAs, ADAR) je grupa proteina s enzimatskom funkcijom deaminacije adenozina u inozin, na dvolančanim RNA molekulama, što posljedično mijenja njihovu strukturu i funkciju. ADAR1 je član ADAR obitelji te znani modulator imunosnog odgovora. Stoga, ADAR1 može pokazivati proviralne i antiviralne učinke, tijekom virusnih infekcija. ADAR1 posjeduje dvije funkcionalno aktivne izoforme: p110 (konstitutivno eksprimiran u stanicama) te p150 (ekspresija potaknuta interferonima (IFN)). Kako bi dodali nova saznanja u područje istraživanja koje se bavi s HSV-1 virusom, istražili smo mogu li ADAR1 proteini pokazivati mogućnost promjene njihovog unutarstaničnog položaja, tijekom rane produktivne faze HSV-1 infekcije. Najprije smo, korištenjem imunofluorescencije te metode unutastaničnoga frakcioniranja , odredili ADAR1 ekspresijski profil u RPE1 stanica, koje nisu bile niti tretirane niti inficrane (engl. „MOCK“). Rezultati ukazuju na to da su obje izoforme ADAR1 proteina ponajviše eksprimirane u jezgri MOCK inficiranih RPE1 stanica. Metode imunofluorescnecije te unutarstaničnoga frakcioniranja koristili smo i za ispitivanje moguće translokacije ADAR1 proteina, unutar prva 24 sata nakon infekcije. Dobiveni rezultati pokazuju da ADAR1 p110 izoforma prelazi iz jezgre u citoplazmu inficiranih stanica, u vremenskom intervalu između 7 i 24 sata nakon infekcije. Nasuprot tome, ekspresija p150 izoforme se smanjuje tijekom prvoga dana infekcije, u jezgri kao i u citoplazmi. Nakon toga, pokušali smo usporediti staničnu ekspresiju ADAR1 proteina između MOCK te inficiranih RPE1 stanica. Također smo analizirali razinu ekspresije proteina, tijekom prva 24 sata infekcije, u različitim staničnim linijama. Svi dobiveni rezultati, uz analizu ADAR1 transkripta, ukazuju na to da se ekspresija ADAR1 proteina ne povećava tijekom rane, produktivne HSV-1 infekcije. No ipak, povećana ekspresija obje ADAR1 izoforme, potaknuta s IFN-β, ne doprinosi povećanoj količini ADAR1 proteina u citoplazmi. Taj rezultat je potvrđen preko imunofluorescencije i „Western blot“ metode. Generano, opisani rezultati ukazuju na translokaciju ADAR1 p110 proteina iz jezgre u citoplazmu RPE1 stanica te da navedeni fenotip nije uzrokovan povećanom ekspresijom proteina
HSV-1 infekcija dovodi do redistribucije jezgrene ADAR1 p110 izoforme
No full textHerpes simplex virus 1 (HSV-1) is a dsDNA virus, which causes many different pathological conditions in the human population. The virus has the ability to modulate host immune response, which enables its replication. Adenosine deaminase acting on RNAs (ADAR) proteins are enzymes, whose main function is deamination of adenosine to inosine on dsRNA molecules, which consequently alters their structure and function. ADAR1 is the member of ADAR family, which is a known modulator of the immune response. Therefore, ADAR1 can exhibit proviral and antiviral effects, during viral infections. ADAR1 possesses two functionally active isoforms: p110 (constitutively expressed) and p150 (expression induced with the interferons (IFNs)). To add new insights to the HSV-1 field of research, we investigated whether ADAR1 proteins exhibit the ability to change their subcellular localisation during the early phase of HSV-1 productive infection. Firstly, by using the immunofluorescence and subcellular fractionation methods, we determined the ADAR1 expression profile of MOCK infected RPE1 cells. Results show that both p110 and p150 isoforms localise mainly in the nucleus of uninfected and unstimulated RPE1 cells. We also used immunofluorescence and subcellular fractionation to examine whether the translocation of ADAR1 proteins happens during first 24 hours after the infection. These results show that ADAR1 p110 isoform translocates from the nucleus to the cytoplasm, at a time point between 7 and 24 hours after infection. On the other hand, p150 isoform depletes in both the nucleus and the cytoplasm during the first day of the infection. Afterwards, we tried to compare cellular expression of ADAR1 isoforms between MOCK and HSV-1 infected RPE1 cells. Also, we analysed expression profile of ADAR1 proteins, during first 24 hours after infection, in several different cell lines. These data, together with the ADAR1 transcriptome analysis, show that the expression of ADAR1 proteins does not elevate during the early phase of HSV-1 productive infection. Nonetheless, increased expression of both ADAR1 isoforms, induced by the IFN-β, does not contribute to increased amounts of ADAR1 proteins in the cytoplasm. This was confirmed by the immunoflurescence and Western blot method. Overall, described results indicate that ADAR1 p110 translocates from the nucleus to the cytoplasm of RPE1 cells, and that this phenotype is not caused by the increase in protein's expression.Herpes simpleks virus 1 (HSV-1) je dvolančani DNA virus, koji uzrokuje više različitih patofizioloških stanja u ljudskoj populaciji. Virus ima sposobnost moduliranja imunosnog odgovora domaćina, što omogućuje njegovu replikaciju. Adenozin deaminaza koja djeluje na RNA (engl. Adenosine deaminase acting on RNAs, ADAR) je grupa proteina s enzimatskom funkcijom deaminacije adenozina u inozin, na dvolančanim RNA molekulama, što posljedično mijenja njihovu strukturu i funkciju. ADAR1 je član ADAR obitelji te znani modulator imunosnog odgovora. Stoga, ADAR1 može pokazivati proviralne i antiviralne učinke, tijekom virusnih infekcija. ADAR1 posjeduje dvije funkcionalno aktivne izoforme: p110 (konstitutivno eksprimiran u stanicama) te p150 (ekspresija potaknuta interferonima (IFN)). Kako bi dodali nova saznanja u područje istraživanja koje se bavi s HSV-1 virusom, istražili smo mogu li ADAR1 proteini pokazivati mogućnost promjene njihovog unutarstaničnog položaja, tijekom rane produktivne faze HSV-1 infekcije. Najprije smo, korištenjem imunofluorescencije te metode unutastaničnoga frakcioniranja , odredili ADAR1 ekspresijski profil u RPE1 stanica, koje nisu bile niti tretirane niti inficrane (engl. „MOCK“). Rezultati ukazuju na to da su obje izoforme ADAR1 proteina ponajviše eksprimirane u jezgri MOCK inficiranih RPE1 stanica. Metode imunofluorescnecije te unutarstaničnoga frakcioniranja koristili smo i za ispitivanje moguće translokacije ADAR1 proteina, unutar prva 24 sata nakon infekcije. Dobiveni rezultati pokazuju da ADAR1 p110 izoforma prelazi iz jezgre u citoplazmu inficiranih stanica, u vremenskom intervalu između 7 i 24 sata nakon infekcije. Nasuprot tome, ekspresija p150 izoforme se smanjuje tijekom prvoga dana infekcije, u jezgri kao i u citoplazmi. Nakon toga, pokušali smo usporediti staničnu ekspresiju ADAR1 proteina između MOCK te inficiranih RPE1 stanica. Također smo analizirali razinu ekspresije proteina, tijekom prva 24 sata infekcije, u različitim staničnim linijama. Svi dobiveni rezultati, uz analizu ADAR1 transkripta, ukazuju na to da se ekspresija ADAR1 proteina ne povećava tijekom rane, produktivne HSV-1 infekcije. No ipak, povećana ekspresija obje ADAR1 izoforme, potaknuta s IFN-β, ne doprinosi povećanoj količini ADAR1 proteina u citoplazmi. Taj rezultat je potvrđen preko imunofluorescencije i „Western blot“ metode. Generano, opisani rezultati ukazuju na translokaciju ADAR1 p110 proteina iz jezgre u citoplazmu RPE1 stanica te da navedeni fenotip nije uzrokovan povećanom ekspresijom proteina
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
Experimental models for multiple sclerosis
No full textMultipla skleroza (MS) je autoimuna bolest koja uzrokuje demijelinizaciju aksona središnjeg živčanog sustava (SŽS). Na razvoj bolesti utječu različiti genetički i okolišni čimbenici, stoga MS spada u multifaktorijalne složene bolesti. Autoreaktivne stanice imunosnog sustava uzrokuju autoimuni odgovor u SŽS-u koji rezultira razaranjem mijelinske ovojnice te je prijenos akcijskog potencijala niz neuron usporen. Uz demijelinizaciju, glavne značajke bolesti su i neurodegeneracija aksona koja nastupa u kasnijim fazama bolesti, glioza te upala u SŽS-u. Simptomi bolesti uključuju gubitak motoričkih, senzoričkih i autonomnih funkcija. Bolest se po intenzitetu simptoma i njihovom razvoju u vremenu dijeli na: klinički izolirani sindrom (CIS), relapsno-remitirajuću multiplu sklerozu (RRMS), primarno-progresivnu multiplu sklerozu (PPMS) i sekundarno-progresivnu multiplu sklerozu (SPMS). RRMS je najčešći oblik MS-a. Za istraživanje složene bolesti poput MS-a potrebni su odgovarajući in vivo animalni modeli. Glavni animalni model istraživanja MS-a je eksperimentalni autoimuni encefalomijelitis (EAE). Kao i MS, karakterizira ga autoimuni odgovor te demijelinizacija i oštećenja aksona u SŽS-u. Najčešće životinje u kojima je induciran EAE jesu miševi i štakori. Postoji nekoliko različitih metoda indukcije EAE-a, no najčešće su aktivna i pasivna imunizacija životinja. Za razliku od CD8+ citotoksičnih T limfocita u MS-u, glavni nositelji patogeneze EAE-a su CD4+ pomagački T limfociti. To čini EAE model vrlo korisnim u istraživanju njihovih efektorskih funkcija te regulacijskih T limfocita. Nadalje, EAE modeli važni su u detekciji potencijalnih antigena koji sudjeluju u autoimunome odgovoru te mehanizmima kojima dolazi do upale i demijelinizacije. Najveći nedostaci EAE-a u istraživanju MS-a su lokalizacija lezija u kralježničnoj moždini, za razliku od dominantnih moždanih lezija u pacijentima koji boluju od MS-a. te nedostatak progresivnosti simptoma. EAE je glavni animalni model MS-a koji je zaslužan za dobivanje velike većina saznanja o patofioziologiji bolesti te razvoju terapije za pacijente koji boluju od MS-a.Multiple sclerosis (MS) is an autoimmune disease, which causes demyelination of axons in central nervous system (CNS). Many different genetic and enviromental factors affect disease develompent, hence MS belongs to multifactorial, complex diseases. Autoreactive immune cells cause autoimmune response in CNS which results in myelin sheath destruction and this slowes down action potential conduction along neurons. Beside demyelination, another elements of MS are neuroaxonal degeneration which occurs in later stages of the disease, gliosis and CNS inflammation. Disease symptoms include loss of motor, sensory and autonomic functions. Disease is divided, by its symptoms intensity and development through the time, to: clinically isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RRMS), primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS). RRMS is most common type of MS. For the research of complex diseases, like MS, animal in vivo models are required. The main animal model for MS research is experimental autoimmune encephalomyelitis (EAE). Just like MS, it is characterised by autoimmune response, demyelination and axonal damage in CNS. Most used animals in EAE research are mice and rats. There are several different methods of EAE induction, but the most common are active and passive immunisation of animals. Unlike CD8+ cytotoxic T lymphocytes in MS, main carriers of the EAE pathogenesis are CD4+ T helper lymphocytes. That makes EAE very useful in their effector functions and regulatory T cells research. Furthermore, EAE models are important in detection of potential antigens, which participate in autoimmune response and mechanisms which induce inflammation, and demyelination. Main disadvantages of EAE as a model of MS research are localization of lesions in spinal cord, unlike dominant brain lesions in MS patients, and lack of symptoms progression. EAE is the main animal model of MS which is responisble for the vast majority of pathophysiologic knowledge about the disease and for development of MS therapy
HSV-1 infekcija dovodi do redistribucije jezgrene ADAR1 p110 izoforme
No full textHerpes simplex virus 1 (HSV-1) is a dsDNA virus, which causes many different pathological conditions in the human population. The virus has the ability to modulate host immune response, which enables its replication. Adenosine deaminase acting on RNAs (ADAR) proteins are enzymes, whose main function is deamination of adenosine to inosine on dsRNA molecules, which consequently alters their structure and function. ADAR1 is the member of ADAR family, which is a known modulator of the immune response. Therefore, ADAR1 can exhibit proviral and antiviral effects, during viral infections. ADAR1 possesses two functionally active isoforms: p110 (constitutively expressed) and p150 (expression induced with the interferons (IFNs)). To add new insights to the HSV-1 field of research, we investigated whether ADAR1 proteins exhibit the ability to change their subcellular localisation during the early phase of HSV-1 productive infection. Firstly, by using the immunofluorescence and subcellular fractionation methods, we determined the ADAR1 expression profile of MOCK infected RPE1 cells. Results show that both p110 and p150 isoforms localise mainly in the nucleus of uninfected and unstimulated RPE1 cells. We also used immunofluorescence and subcellular fractionation to examine whether the translocation of ADAR1 proteins happens during first 24 hours after the infection. These results show that ADAR1 p110 isoform translocates from the nucleus to the cytoplasm, at a time point between 7 and 24 hours after infection. On the other hand, p150 isoform depletes in both the nucleus and the cytoplasm during the first day of the infection. Afterwards, we tried to compare cellular expression of ADAR1 isoforms between MOCK and HSV-1 infected RPE1 cells. Also, we analysed expression profile of ADAR1 proteins, during first 24 hours after infection, in several different cell lines. These data, together with the ADAR1 transcriptome analysis, show that the expression of ADAR1 proteins does not elevate during the early phase of HSV-1 productive infection. Nonetheless, increased expression of both ADAR1 isoforms, induced by the IFN-β, does not contribute to increased amounts of ADAR1 proteins in the cytoplasm. This was confirmed by the immunoflurescence and Western blot method. Overall, described results indicate that ADAR1 p110 translocates from the nucleus to the cytoplasm of RPE1 cells, and that this phenotype is not caused by the increase in protein's expression.Herpes simpleks virus 1 (HSV-1) je dvolančani DNA virus, koji uzrokuje više različitih patofizioloških stanja u ljudskoj populaciji. Virus ima sposobnost moduliranja imunosnog odgovora domaćina, što omogućuje njegovu replikaciju. Adenozin deaminaza koja djeluje na RNA (engl. Adenosine deaminase acting on RNAs, ADAR) je grupa proteina s enzimatskom funkcijom deaminacije adenozina u inozin, na dvolančanim RNA molekulama, što posljedično mijenja njihovu strukturu i funkciju. ADAR1 je član ADAR obitelji te znani modulator imunosnog odgovora. Stoga, ADAR1 može pokazivati proviralne i antiviralne učinke, tijekom virusnih infekcija. ADAR1 posjeduje dvije funkcionalno aktivne izoforme: p110 (konstitutivno eksprimiran u stanicama) te p150 (ekspresija potaknuta interferonima (IFN)). Kako bi dodali nova saznanja u područje istraživanja koje se bavi s HSV-1 virusom, istražili smo mogu li ADAR1 proteini pokazivati mogućnost promjene njihovog unutarstaničnog položaja, tijekom rane produktivne faze HSV-1 infekcije. Najprije smo, korištenjem imunofluorescencije te metode unutastaničnoga frakcioniranja , odredili ADAR1 ekspresijski profil u RPE1 stanica, koje nisu bile niti tretirane niti inficrane (engl. „MOCK“). Rezultati ukazuju na to da su obje izoforme ADAR1 proteina ponajviše eksprimirane u jezgri MOCK inficiranih RPE1 stanica. Metode imunofluorescnecije te unutarstaničnoga frakcioniranja koristili smo i za ispitivanje moguće translokacije ADAR1 proteina, unutar prva 24 sata nakon infekcije. Dobiveni rezultati pokazuju da ADAR1 p110 izoforma prelazi iz jezgre u citoplazmu inficiranih stanica, u vremenskom intervalu između 7 i 24 sata nakon infekcije. Nasuprot tome, ekspresija p150 izoforme se smanjuje tijekom prvoga dana infekcije, u jezgri kao i u citoplazmi. Nakon toga, pokušali smo usporediti staničnu ekspresiju ADAR1 proteina između MOCK te inficiranih RPE1 stanica. Također smo analizirali razinu ekspresije proteina, tijekom prva 24 sata infekcije, u različitim staničnim linijama. Svi dobiveni rezultati, uz analizu ADAR1 transkripta, ukazuju na to da se ekspresija ADAR1 proteina ne povećava tijekom rane, produktivne HSV-1 infekcije. No ipak, povećana ekspresija obje ADAR1 izoforme, potaknuta s IFN-β, ne doprinosi povećanoj količini ADAR1 proteina u citoplazmi. Taj rezultat je potvrđen preko imunofluorescencije i „Western blot“ metode. Generano, opisani rezultati ukazuju na translokaciju ADAR1 p110 proteina iz jezgre u citoplazmu RPE1 stanica te da navedeni fenotip nije uzrokovan povećanom ekspresijom proteina
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
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