Consortium of Estonian Libraries Network

International Conference on Library Automation in Central & Eastern Europe April 11 - 13, 1996, Budapest, Hungar

Endomeetriumi ja endometrioosikollete molekulaarse profiili iseloomustamine

Väitekirja elektrooniline versioon ei sisalda publikatsioone.Endometrioos on tõsine günekoloogiline haigus, mida iseloomustab emaka limaskesta ehk endomeetriumi koe kasvamine kolletena väljaspool emakaõõnt. Vaatamata intensiivsetele uuringutele on siiani ebaselge, miks endometrioosikolded moodustavad ja millised on need molekulaarsed muutused, mis haiguse kujunemisele kaasa aitavad. Endometrioosi tekkemehhanismide väljaselgitamist on oluliselt hõlbustanud mikrokiibi- ja sekveneerimistehnoloogiate kiire areng, mis võimaldavad ülevaatlikult kirjeldada molekulaarseid muutuseid endometrioosikolletes ja endomeetriumis. Varasemad suure läbilaskevõimega tehnoloogiatel põhinevad endometrioosi uuringud on paraku jõudnud vastukäivate tulemusteni, mis viitab suure tõenäosusega erinevustele katsete disainis ja seetõttu on väga oluline juba uuringut planeerides pöörata tähelepanu võimalikele kitsaskohtadele. Antud töö eesmärgiks oli leida endometrioosi kujunemist mõjutavaid geneetilisi, epigeneetilisi ja mikroRNAde tasemete muutuseid nii endometrioosikolletes kui ka endomeetriumis, kasutades selleks hoolikalt valitud katseskeemi ja mikrokiipidel ning süvasekveneerimisel põhinevaid tehnoloogiaid. Töö tulemuste põhjal võime järeldada, et kromosomaalsed ümberkorraldused endometrioosikolletes ja endomeetriumis ning muutused endomeetriumi DNA metülatsioonimustris ei ole endometrioosi kujunemise esmasteks põhjusteks. Leidsime viis endometrioosikolletes kõrgelt ekspresseeritud mikroRNAd, mille taseme määramine võimaldab ilma histoloogiliste uuringuteta koldeid tuvastada. See uuring tõi välja ka uuringudisaini olulisuse, näidates et kollete mikroRNA tasemete määramiseks tuleb arvesse võtta kollet ümbritseva koe normaalset mikroRNA profiili. Samuti näitasime, et menstruaaltükli jooksul toimuvad endomeetriumi DNA metülatsioonimustris olulised muutused, mida tuleb haigusseoseliste markerite otsimisel kindlasti arvestada.Endometriosis is a serious gynaecological disease characterized by the growth of functional endometrial tissue outside the uterus. Despite of extensive research it is still unclear why endometriosis develops and what are the molecular events triggering the implantation of endometrial cells into the wrong location. The fast development of microarray and sequencing-based technologies has opened new possibilities to describe molecular changes in endometriotic lesions and endometria of endometriosis patients. However, previous high-throughput studies in endometriosis have provided conflicting results, most probably due to the differences in study design and therefore, it is extremely important to pay attention to possible shortcomings before planning the study. The aim of our study was to find genetic, epigenetic and microRNA markers in endometriotic lesions and endometrial tissue that contribute to the endometriosis development, by using carefully planned study design and high-throughput analysis methods. Based on the results of our study we propose that chromosomal alterations in endometriotic lesions and endometrium and changes in endometrial DNA methylation are not the key events responsible for disease development. In microRNA study, signature of five upregulated microRNAs in endometriotic lesions that enable correct diagnosis of endometriotic lesions without the need for traditional histological evaluation of tissue biopsy, was found. Also, the results of this study accentuated the relevance of study design and indicated that for identification of lesion specific miRNAs the normal miRNA signature of healthy tissue should be considered. Furthermore, we found that normal epigenetic changes occurring in endometrium across the menstrual cycle phases should be considered when looking for disease-specific DNA methylation markers

AIRE mõju geeniekspressioonile – transkriptsiooni regulatsiooni mehhanismi uuringud koekultuuri rakkudes

Väitekirja elektrooniline versioon ei sisalda publikatsiooneProbleemi kirjaldus. Immuunsüsteemi põhiline ülesanne on võidelda haigustekitajatega, mis üritavad tungida organismi, et seda kahjustada. Samaväärselt oluline on immuunsüsteemi võime hoiduda kehaomaste või väljastpoolt tulevate kahjutute molekulide vastu suunatud immuunreaktsioonist. Seda nähtust nimetatakse immuuntolerantsuseks. Immuuntolerantsuse kujunemisel on suur roll harknäärmel, mis vastutab kehaomaste valkude suhtes tundlike T-rakkude kõrvaldamise eest. Suuresti sõltub see protsess ühest valgust nimega autoimmuunsuse regulaator (AIRE). AIRE olemasolul avalduvad harknäärmes kehaomased valgud, mis viiakse kokku arenevate T-rakkudega. T-rakk, millel tekib tugev reaktsioon nende valkude suhtes, sureb enne, kui jõuab harknäärmest lahkuda. Kui harknäärmes puudub AIRE, jäävad ohtlikud T-rakud ellu, siirduvad vere- ning lümfiringe kaudu teistesse kudedesse ja vallandavad autoimmuunrünnaku, mis hävitab koe, põhjustades seeläbi raskeid haiguseid. Tulemus ja kasutegur. Käesolevas doktoritöös uurisime, kuidas mõjutab AIRE funktsiooni see, kui valgule lisada biokeemilisel viisil atsetüülrühmasid. Leidsime, et muutuvad AIRE paiknemine rakutuumas, valgu stabiilsus ning võime aktiveerida kehaomaste valkude avaldumist. Lisaks analüüsisime AIRE valgus esinevat mutatsiooni, mis põhjustab inimestel AIRE-puudulikkusest tingitud autoimmuunhaigust. Selgus, et mutatsioon lõhub AIRE valgu struktuuri ning kuigi AIRE on rakus olemas, ei pääse ta rakutuuma, et kehaomaste valkude avaldumist aktiveerida. Doktoritöö viimases osas keskendusime muutustele genoomi struktuuris, mis kaasnevad AIRE poolt aktiveeritud kehaomaste valkude avaldumisega. Avastasime vastupidiselt ootustele, et muutused toimuvad kehaomaste valkude geenidest kaugel olevates genoomiosades, viidates sellele, et AIRE-l on seni teadaolevast palju laialdasem mõju genoomi ülesehitusele. Kokkuvõtvalt, uurides AIRE valku mõjutavaid tegureid ning AIRE enda toimet genoomi struktuurile, suudame paremini mõista immuuntolerantsuse ning autoimmuunhaiguste tekkemehhanisme.Description of the problem. The main function of the immune system is to fight off pathogens that try to invade and harm the body. At the same time, the immune system has to block any immune reactions against harmless antigens stemming from the organism itself or from the environment. This phenomenon is called immune tolerance. The thymus plays a major role in establishing tolerance towards self-antigens by eliminating autoreactive T-cells. This process is primarily controlled by a single protein called autoimmune regulator (AIRE). AIRE promotes the expression of self-antigens that are presented to developing T-cells in the thymus. T-cell that strongly react to the self-antigens, will die before they leave the thymus. If AIRE is absent from the thymus, then the self-reactive T-cells will survive and migrate to other tissues, which can be targeted and destroyed by these T-cells causing an autoimmune disease. Result and benefit. In this thesis, we investigated the effect of acetylation of the AIRE protein. We found that it alters the localisation and stability of the protein and eventually affects the expression of self-antigens. Additionally, we analysed a mutation in the AIRE protein that causes AIRE-deficiency and autoimmunity in humans. We conclude that the mutation destroys AIRE protein structure, and although AIRE is still present in the cells, it cannot move into the nucleus to activate the expression of self-antigens. In the final part of the thesis we explored the changes in the structure of the genome that coincide with the AIRE-dependent activation of self-antigen expression. Contrary to expectations, the genomic alterations occurred far away from self-antigen coding genes suggesting that AIRE has a much broader impact on the gene regulatory processes in the nucleus than previously anticipated. In summary, uncovering factors that affect AIRE function and how AIRE itself contributes to the genomic organisation expand our understanding of the molecular mechanisms behind immune tolerance and autoimmunity

Mobile system for managing and mitigating the accommodation problems among students in Universiti Utara Malaysia (UUM)

Students either local or international experience different adjustment problems while moving one place to another place, and out of those problems, finding suitable accommodation is the most challenging one. However, at Universiti Utara Malaysia (UUM), the accommodation center for the students utilizing the traditional method for managing and processing the issues related to the students’ accommodation. Therefore, this project seeks to exploit the mobile technologies to enhance the accommodation process and increase the communication among the students and management of the resident. This project has three core objectives: identifying the requirements, analysis and designing, and evaluating the usability of the mobile accommodation system (MAS). To evaluate the usability of the MAS, a usability scale is used and feedbacks were collected from 40 students around the UUM campus. The results have revealed that the users strongly accepted and are satisfied with the interface functions, usability, integrity and other facilities for the application. Thus, students and accommodations staff can use the applications for managing their accommodation with successfully

An analysis of amenity-led rural economic *development in northeast region: A spatial simultaneous equations approach

In a matter of just a few decades, the economic landscape of rural America has changed in fundamental ways. Industries once considered the backbone of rural economies have been transformed by globalization and marketing. Others, such as tourism and amenity-based economies or the service sector, have emerged to replace the traditional natural resource and manufacturing-based economies. These changes have invigorated some areas, and forever altered others. Consequently, Interest in an amenity focused development strategy has exploded as policymakers and community leaders realize that most of the jobs lost in recent decades will not return. Instead, these leaders are looking inside their communities for new sources of economic growth.;In an effort to analyze the role of natural and recreational amenities in rural economic growth, this study develops a simultaneous-equation system under the assumptions of profit maximization of firms and utility maximization of households as well as the neoclassical assumption of equilibrium growth in a partial lag-adjustment growth-equilibrium framework. Past studies assume that amenities have a direct and independent effect on economic growth, but in reality the availability of high amenity levels alone can only create the opportunity for economic growth. But to be an effective development tool it should be coupled with factors that can exploit its existence, encourage its use, and give it a comparative advantage.;This research extends existing studies in this area by incorporating interaction terms that account for the combined impact of amenities with proximity to metropolitan areas and accessibility (Interstate highway density). Furthermore, the study contributes to the amenity and regional growth literature by estimating a simultaneous spatial Durbin model using the two stages least square method. Historical and cultural amenities and water based recreational amenities are found to play a positive role in shaping the growth of population in the northeast region of the US. The role of natural amenities, land and winter based amenities is found to be negative or insignificant. One of the important findings of the study is the positive role of surrounding counties historical and cultural amenities in the growth of population and employment densities. Overall there is no evidence of a consistent and strong relationship and the results can be termed as mixed and inconclusive

Tsirkuleeriva rakuvaba DNA metülatsioonitaseme muutused kopsuvähi biomarkerina

Käesoleva töö käigus töötati välja naatriumbisulfit-töötlusel, multipleks PCR-il ja amplikonipõhisel teise põlvkonna sekveneerimisel põhinev töövoog metülatsioonitaseme määramiseks cfDNA-s. Seejärel rakendati meetodit 32 kopsuvähiga uuritavate cfDNA ja buffy kihi DNA peal. Katsete tulemusena järeldati, et tsirkuleeriva rakuvaba DNA metülatsioonitaseme muutuste analüüsimine on potentsiaalselt kasutatav kopsuvähi diagnostilise biomarkerina

Wine grapes phenological maturity depending on cultivar and spring covers

Magistritöö Aianduse õppekavalPõhjamaises viinamarjakasvatuses on probleemiks jahedad ilmad ja hilisöökülmad kevadel. Kevadkatetega saab kaitsta öökülmade eest taimi ja jahedate ilmadega õisi. Eelnevalt on Maaülikoolis uuritud erinevaid kattematerjale ja on selgunud, et katte mõju oleneb nii kattematerjalist kui ka viinapuu sordist. Uurimustöö eesmärk oli selgitada välja sordiomaduste ja kevadkatete mõju veiniviinamarjasortide ’Rondo’, ’Hasanski Sladki’ ja ’Zilga’ saagi fenoloogilise küpsuse parameetritele. Katse viidi läbi 2019. aastal Eesti Maaülikooli Rõhu Katsejaamas avamaa tingimustes. Kattematerjalidena kasutati varjutuskangast ja talveloori. Sordil ’Hasanski Sladki’ oli talvelooriga ja katteta katsevariant. Sordil ’Zilga’ oli talvelooriga ja varjutuskangaga katsevariant. Kevadkatted paigaldati 6. mail ja eemaldati 26. juunil. Sordivõrdluses olid sordid ’Rondo’, ’Zilga’ ja ’Hasanski Sladki’. Sordiomadused mõjutasid veiniviinamarjade fenoloogilise küpsuse peamisi parameetreid, nagu fenoolide üldsisaldus, antotsüaanide üldsisaldus ja antioksüdatiivne aktiivsus. Suurima fenoolide sisaldusega oli sort ’Rondo’, väikseimaga sort ‘Zilga’. Antotsüaanide sisaldus oli suurim sordil ‘Rondo’ väikseim sordil ‘Zilga’. Kevadkatted mõjutasid oluliselt fenoloogilise küpsuse parameetreid. ’Zilga’ puhul oli fenoolide ja antotsüaanide sisaldus ja antioksüdatiivne aktiivsus talvelooriga variandis oluliselt suurem. ’Hasanski Sladki’ fenoolide ja antotsüaanide sialadus oli katteta variandis oluliselt suurem, kui talvelooriga variandis. Antioksüdatiivset aktiivsust kevadkate ei mõjutanud.The problem in Nordic viticulture is the cold weather and night frosts in the spring. With spring covers, plants can be protected from night frosts in spring and flowers can be protected during flowering in cold weather. Previous studies at the University of Life Sciences have focussed on the cover materials and it has been found that the effect of the cover depends on both the material of the cover and the variety of the vine. The aim of the study was to determine the effect of cultivar characteristics and spring covers on the phenological maturity parameters of the ‘Rondo’, ‘Hasanski Sladki’ and ‘Zilga’ wine grape varieties. The experiment was conducted in 2019 at the Estonian University of Life Sciences' Pressure Experiment Station in open field conditions. Shade cloth and frost blanket were used as cover materials. Frost blanket and no shade cloth were used on ‘Hasanski Sladki’, while both frost blanket and shade cloth were used on ‘Zilga’. The spring covers were installed on May 6 and removed on June 26. The grapevine 'Rondo', 'Zilga' and 'Hasanski Sladki’ were used for the cultivar comparison in this study. Varietal characteristics affected the main parameters of the phenological maturity of the wine grapes, such as total phenols, total anthocyanins and antioxidant activity. The ‘Rondo’ variety had the highest phenol content and the ‘Zilga’ had the lowest. The anthocyanin content was highest in the ‘Rondo’ and the lowest in the ‘Zilga’. There was a statistically significant difference between the three varieties in terms of phenol content, anthocyanin content and antioxidant activity. Spring covers significantly affected the parameters of phenological maturity. In the case of ‘Zilga’, the content of phenols, anthocyanins and the antioxidant activity were significantly higher in the frost blanket variant. The content of phenols and anthocyanins in ‘Hasanski Sladki’ were significantly higher where no cover cloth was used than in the variant where frost blanket was utilised. The antioxidant activity was not affected by the spring covers