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Tsentraalse tolerantsuse eest vastutavad transkriptsioonilised protsessid tüümuses
Get PDFVäitekirja elektrooniline versioon ei sisalda publikatsiooneImmuunsüsteemi üheks alustalaks on T-rakkude võime eristada haigustekitajatest pärinevaid („võõraid“) valke kehaomastest („omadest“) valkudest. Selle eristusvõime tagab immuuntolerantsuse mehhanism, mis jaguneb tolerantsust tekitava keskkonna põhjal kaheks: tsentraalseks ja perifeerseks tolerantsuseks. Tsentraalse T-rakulise tolerantsuse tekkepaigaks on südame ees asuv organ, tüümus ehk harknääre, kus arenevaid T-rakke „õpetatakse“ vältima immuunvastust „omale“. Selles protsessis on keskne roll tüümuse epiteelirakkudel ja neis rakkudes avalduvatel valgufaktoritel, nn transkriptsioonifaktoritel, mis reguleerivad teisi geene ja mille osalusel tehakse kahjutuks „oma“ valkudega reageerivad T-rakud. Üheks oluliseks transkriptsioonifaktoriks on Autoimmuunsuse Regulaator (Aire), mille mutatsiooni puhul T-rakud reageerivad „omale“ ning patsientidel tekivad mitmeid organeid mõjutavad autoimmuunsed haigused. Seega aitab tüümuses avalduvate transkriptsioonifaktorite uurimine paremini mõista immuunsüsteemi haigusi, kus „oma“ ja „võõra“ eristamine on häiritud, nagu autoimmuunhaigused ning iseeneslikud raseduse katkemised.
Käesolev töö keskendus tüümuse epiteelis tsentraalse tolerantsuse ja seega immuunsüsteemi terviklikku toimimist mõjutavate geenide regulatsiooni uurimisele. Tuvastasime imetajate genoomis geenidevahelise piirkonna, ilma milleta ei ole Aire avaldumine tüümuses võimalik. Leidsime ka, et tiinuse ajal muutub tüümuses olevate epiteelirakkude arv ja geenide avaldumine sedavõrd, et väheneb võime meelitada tüümusesse T-rakkude eellasrakke ning suunata nende arengut. Käesoleva töö viimases osas leidsime, et lisaks Aire-le on tüümuse epiteelis teine transkriptsioonifaktor, Irf4, mis otseselt mõjutab tüümuses T-rakulist tolerantsust.A functional immune system is capable of reacting to antigens from invading pathogens (non-self) and maintaining immune tolerance towards autologous (self) and beneficial or benign foreign antigens. Immune tolerance is divided into central or peripheral tolerance depending on the time and site of induction. One of the two sites for central tolerance induction is an organ called thymus, where maturating T cells are taught to avoid reaction to self-antigens. The maturation of all T cells depends on thymic stromal cells, especially thymic epithelial cells that express a protein called Autoimmune Regulator (Aire). Aire regulates the expression of genes that help to eliminate T cells that consider self to be non-self. Mutations in the gene responsible for Aire protein are sufficient to cause a complex autoimmune syndrome affecting multiple organs in the body. Characterizing the mechanisms by which thymic transcription factors induce tolerance helps us to understand conditions such as autoimmune diseases and spontaneous abortions where the immune system is incapable of differentiating between self and non-self
The current thesis concentrates on transcriptional processes in thymic stromal cells that enforce central tolerance and therefore immune system as a whole. We identified an intergenic region critical for the expression of Aire in thymic epithelial cells. We also found pregnancy to affect the numbers and gene expression profiles of thymic stromal cells in a way which renders these cells suboptimal in attracting T cell progenitors into the thymus and directing their maturation. In the last part of the thesis we identified a transcription factor Irf4 to be one of first factors besides Aire that regulates T cell tolerance in the thymic epitheliu
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
Tüümuse rejuveneerimine kasvuhormooni sekretagoogi tesamoreliiniga „musta“ hiire mudelis
No full textAge-related thymic involution is one of the major reasons behind compromised adaptive
immune responses in the elderly. It is characterized by the progressive reduction in thymic
mass, accumulation of adipose tissue within the thymus, and disruption of unique thymic
structure, which results in impaired T cell development and reduced naïve T cell output with
age. Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) treatments have shown
promise in restoring the functionality of the aged thymus albeit with unwanted side effects.
While GH secretagogue (GHS) ghrelin has thymus-rejuvenating effects, the effects of a
similar GHS called tesamorelin have not yet been studied. Since tesamorelin stimulates
endogenous GH production similar to ghrelin and has fewer metabolic side effects than
exogenous GH treatment, we hypothesize that it could have positive effects on thymus
functioning and T cell development. In this study, the effects of tesamorelin on T cell
populations in the thymus, as well as secondary lymphoid organs, were investigated using the
“dirty” mouse model that better resembles the human immune system than conventional SPF
mice. We report that while tesamorelin does not have thymus-rejuvenating effects in the 6.5-
month-old “dirty” mice, it does promote the accumulation of antigen-experienced memory T
cell subsets and decrease of naïve T cell subsets in the murine spleen. Although further
research is required, we suggest this splenic accumulation is the reflection of the decreased
levels of activated cytotoxic T cell markers in the peripheral blood of HIV patients treated
with clinical grade tesamorelin
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
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