1,720,955 research outputs found
Setting up an acute infection model for CVB1 in mice
Get PDFBackground and aims: Coxsackie B viruses (CVB) under Enterovirus (EV) genus are small yet highly contagious human pathogens. CVB infection can cause severe inflammation in multiple organs, including heart and pancreas. Infection is also linked with diseases such as type 1 diabetes (T1D) and dilated cardiopathy (DCM), among others. The pathogenic mechanisms of CVBs and their role in disease aetiologies are not well known. In addition, there are no treatments or vaccines against CVBs. The aim of this thesis is to set up an animal infection laboratory for Tampere University and to set up an acute infection model for CVB1 in mice. Animal infection model would enable research on CVB infection mechanisms, disease associations and testing for preventive strategies.
Methods: CVB1 was produced in Green Monkey Kidney (GMK) cells and purified by ultracentrifugation. Purified virus was characterized with SDS-PAGE, Western blot, Dynamic Light scattering and BCA total protein quantification. Infectivity of the virus was measured with tissue culture infectious dose 50% (TCID50) method. Animal infection laboratory was established, and operating procedures were determined according to risk assessment and mock studies, among other factors. Infection model was established by intraperitoneal inoculation of CVB1 in BALB/c mice. Infection studies were conducted in four separate studies. The model was optimized ac-cording to infectious dose, study length, and sex. The infection was determined from the amount of replicative virus in the pancreas, heart, and blood by TCID50 method. During the studies, wellbeing of the mice was evaluated with body score indexing, and weights were measured daily.
Results: Induction of systemic CVB1 infection in BALB/c mice was successful. Replicative virus was most consistently found in pancreas but was also detected from blood samples until day 4. Viremia increased during the first 4 days post infection (dpi) in female mice. Viral doses 106 and 107 TCID50 per mouse were able to cause infection in the pancreas most consistently. Replicative virus seemed to be cleared from blood and pancreas around 7 dpi. Female mice had higher viral titres in pancreas 4 dpi compared to male mice. Wellbeing of male mice deteriorated during the infections as indicated by diarrhea and ruffled fur. Also, weights decreased significantly. Female mice, on the other hand, did not show external signs of infection and the weights remained similar. Replicative virus was not found in heart at any points of the studies.
Conclusions: The aims of the thesis were successfully completed. The animal infection laboratory was set up and we were able to induce systemic CVB1 infection in mice. For further optimization of the infection model, we should use the optimized viral doses of 106 and 107 TCID50. For detection of replicative virus in pancreas, the infection should be followed 4 dpi. Moreover, our results support the use of female mice to reduce animal suffering. This infection model could further enable conduction of challenge studies, where safety and efficacy of vaccines can be tested. Moreover, established facility would support infection models with different viruses serotypes or modelling CVB induced diseases
Infection mechanism of cox-sackievirus B: Life cycle and strategies for immune evasion
Get PDFCoxsackieviruses B (CVBs) are small yet highly contagious viruses that cause several acute and chronic diseases. Structurally CVBs are small, nonenveloped, positive-sense single-stranded RNA viruses. The virus spreads through the fecal-oral route, and it can cause different diseases from mild cold-like symptoms to severe diseases. CVB infection is one of the major causes of infection-induced myocarditis. It is also strongly linked with type 1 diabetes.
This study aims to overview the virus’s infection mechanism and its counteractions in the cell and immune system. The infection mechanisms include the invasion of the virus, replication, assembly, and release. The virus enters the cell through coxsackievirus- and adenovirus receptors and utilizes the host's machinery for replication and translation. The virus effectively interferes with the host cell by disturbing its metabolisms and preventing transcription.
The virus is recognized by innate immunity through pattern recognition receptors. Detection drives the proper response of adaptive immunity, where B cells have the greatest impact. Nevertheless, CVB has clever ways to evade immunity. Successful evasion can lead to persistent infection as well as to effective spreading of the virus to secondary tissues. Chronic diseases are a result of persistent infections and damaging immune responses. Myocarditis and type 1 diabetes are examples of chronic diseases associated with CVB infection and pancreatic β-cells are demonstrated to be especially susceptible to coxsackievirus B infection. Understanding the infection mechanism of the virus is crucial for designing effective ways to prevent or treat the outcomes of the infection.Coxsackie B -virukset ovat pieniä mutta helposti tarttuvia viruksia, jotka aiheuttavat sekä akuutteja että kroonisia sairauksia. Rakenteellisesti Coxsackie B -virukset ovat vaipattomia RNA-viruksia, joilla on positiivinen yksijuosteinen RNA-genomi. Virus leviää ulosteen ja suun kautta, ja sen aiheuttamien sairauksien oireet vaihtelevat lievistä flunssan kaltaisista oireista vakaviin sairauksiin. Coxsackievirus B on yksi infektion seurauksena kehittyvän sydänlihastulehduksen merkittävimmistä aiheuttajista. Virustartunta on yhdistetty myös tyypin 1 diabeteksen puhkeamiseen.
Tämän tutkielman tavoitteena on antaa yleiskuva viruksen infektiomekanismista ja menetelmistä vaikuttaa isäntäsolun ja immuunipuolustuksen toimintaan. Infektiomekanismi sisältää viruksen tunkeutumisen isäntäsoluun, sen genomin replikaation ja translaation, uusien virusten kokoamisen sekä vapauttamisen solusta joko solun hajottavaa, tai ei-hajottavaa reittiä. Virus pääsee soluun coxsackie- ja adenovirusreseptorin kautta. Virus hyödyntää isäntäsolun komponentteja replikaatioon ja translaatioon. Virus häiritsee isäntäsolua esimerkiksi estämällä sen omaa transkriptiota ja sotkemalla sen metaboliareittejä.
Immuunijärjestelmä tunnistaa viruksen synnynnäiseen immuniteettiin kuuluvien toistokuvioita tunnistavien reseptorien kautta. Viruksen tunnistaminen aiheuttaa adaptiivisen immuunivasteen aktivoimisen, jossa B-soluilla on suurin merkitys virusta vastaan puolustautuessa. Viruksella on kuitenkin monia nokkelia tapoja välttää tunnistetuksi tuleminen. Mikäli virusta vastaan ei synny tarvittavaa immuunivastetta, voi virusinfektio pitkittyä ja levitä sekundäärisiin elimiin. Krooniset sairaudet ovat seurausta pitkittyneistä infektioista ja vahingollisesta immuunivasteesta. Sydänlihastulehdus ja tyypin 1 diabetes ovat esimerkkejä kroonisista sairauksista, joiden kehittymiseen on liitetty Coxsackievirus B -infektio. Varsinkin haiman β-solujen on todistettu olevan erityisen alttiita virusinfektiolle. Infektiomekanismin kokonaisvaltainen ymmärtäminen on
välttämätöntä, jotta virusinfektion ehkäisemiseksi ja lieventämiseksi voidaan kehittää hoitomenetelmiä
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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