DNA metülatsiooni roll kokaiini ravimsõltuvuse väljakujunemises, sõltuvuse avaldumises ja abstinentsis

Väitekirja elektrooniline versioon ei sisalda publikatsiooneRavimsõltuvus on ajuhaigus, milles psühhoaktiivne aine kutsub esile füüsilisi, psüühilisi häireid, sotsiaalse toimimise puudujääki ja töövõimekuse halvenemist. Haigus kujuneb välja aegamööda, tekitades püsivaid neurobioloogilisi muutusi, mis võivad kesta ka pärast sõltuvust tekitavate ainete kasutamise lõpetamist. Korduv psühhostimulaatori (kokaiini) manustamine põhjustab katseloomadel võimendunud käitumisvastuse (käitumusliku sensitisatsiooni), mis modelleerib sõltuvuskäitumist ja kokaiini psühhootilisi komplikatsioone inimesel. Sõltuvuse väljakujunemise riskitegur on varajases elueas kogetud stress. Psühhostimulaatorid põhjustavad muutusi geeniekspressioonis, mõjutades omakorda närviraku ülesehitust, närviimpulsi ülekannet ja närviringide toimimist. DNA metülatsioon on mehhanism rakus, mis vahendab geeniekspressiooni muutusi vastusena keskkonna- ja arengumõjuritele. DNA metüleerimist viivad läbi ensüümid DNA metüültransferaasid (DNMT). Käesoleva doktoritöö eesmärk oli uurida, katseloomade käitumise ja molekulaarsel tasemel, kas kokaiini poolt põhjustatud DNA metülatsiooni muutused võivad olla ravimsõltuvuse tundlikkuse, sõltuvuse avaldumise ja võõrutuse üheks mehhanismiks. Samuti oli doktoritöö eesmärgiks hinnata, kas stress mõjutab DNA metülatsiooni protsesse ajus. Töö tulemused näitasid, et varajase eluea stress suurendab DNMTde ekspressiooni ja ensüümiaktiivsust rottide ajus glükokortikoidi retseptori rakusisese signaalraja kaudu, mis võib viia püsivate geeniekspressiooni muutusteni ja kokaiini tundlikkuse suurenemiseni. Samuti leidsime, et korduva kokaiini manustamine hiirtele suurendab DNMTde ensüümiaktiivsust käitumusliku sensitisatsiooni väljendumis- ja abstinentsifaasis ning osad kokaiinist tingitud DNMTde muutused aju naalduvas tuumas on sarnased muutustele katseloomade leukotsüütides. Dnmt3a geeni vähendamine ajus põhjustas suuremat käitumuslikku sensitisatsiooni selle väljaarenemise, kuid mitte võõrutuse vältel, seega Dnmt3a geenil on oluline roll sõltuvuse väljakujunemise ajal. DNA metülatsioon võib olla oluline sõltuvuse arengus ja võõrutusfaasis säilitamaks muutusi geeniekspressioonis. DNMT aktiivsus võib olla kandidaat kokaiini tarbimise määramisel pärast aine metaboliseerimist.SUD is a brain disease, where a psychoactive substance triggers physical, psychological problems or decrease in social functioning. SUD develops progressively and causes persistent neurobiological changes that may endure after substance use has ceased. Repeated cocaine administration causes an enhanced behavioral response in rodents (behavioral sensitization) that models addictive behavior and psychotic complications of cocaine in humans. Early life stress is a risk factor for the development of SUD. Psychostimulants (e.g. cocaine) cause changes in gene expression that alter neuronal morphology, signaling and the functioning of neural circuits. DNA methylation is a cellular mechanism that mediates gene expression changes in response to environmental and developmental stimuli. The enzymes DNA methyltransferases perform DNA methylation. The aim of the dissertation was to assess on behavioral and molecular level whether cocaine induced changes in DNA methylation may underlie individual sensitivity, expression and abstinence of substance abuse. Additional aim of the dissertation was to evaluate how stress affects DNA methylation in the brain. The results showed that early life stress increases DNMT expression and enzyme activity in rodent brain via an intracellular signaling pathway of glucocorticoid receptor that may lead to persistent changes in gene expression and increased sensitivity to cocaine. We also found that repeated cocaine administration to mice increased DNMT activity in the expression and abstinence of behavioral sensitization and some cocaine-induced DNMT changes in the nucleus accumbens are similar to changes in mice leukocytes. Reduction in Dnmt3a gene expression increased behavioral sensitization, but not during abstinence, thus Dnmt3a has an important role during the development of SUD. DNA methylation may be important in the development and abstinence phase of drug abuse to maintain changes in gene expression. DNMT activity may be a candidate for determining cocaine use after the drug has been metabolized.https://www.ester.ee/record=b535860

Sotsiaalse infrastruktuuri arendamine Eestis Euroopa Liidu toetuste abil : dissertatsioon Euroopa õpingute magistrikraadi taotlemiseks

http://tartu.ester.ee/record=b2576724~S1*es

Ööklubid sotsiaalsete suhete (taas)loojana

The title of my research paper is “Night clubs as (re)creators of social relationships”. Whilst nightclubs have gained popularity amongst youth, studying this field helps to understand their way of thinking and acting. My work concentrates on creating and recreating acquaintances in the nightclub, on what kind on stereotypes people use to describe clubs and on how much people identify themselves through the nightclubs. My research relies on earlier studies conducted by Allaste (2005), Nigul (2004), myself and Kirikmäe (2005). The most important theoretical concepts are “stereotypes”, “identity” and “social categorising” which are all expounded in the first part of my work. The method I chose to gather information with is semi-structured interview. This method did not set too clear boundaries for people I interviewed, so they had a chance to express their experience, opinions and thoughts more freely. I interviewed 13 young people (aged 20-23), 5 male and 8 female. All of them had visited a night club more than six times during the past six months. They favoured mainly alternative music and were college students. I found out following: nightclubs are a common place to meet new people. Respondents considered it to be convenient because of the security, you are free to end any contacts with strangers and people visiting the same club have usually something in common. There are also some negative aspects in creating new acquaintances like the loud music, befuddled customers and the superficiality of the contact. 10 out of 13 respondents had made an acquaintance (which lasted longer than one night) and 11 out of 13 knew someone who had made an acquaintance in a night club. Most people I interviewed said that clubs are a common place to meet old friends one has not seen for a long time. They also paid more attention to them than they would have in the street. In clubs individuals have more time, they are usually in good mood and more open minded. All that helps to overcome the distance time may have created. Stereotypes are very popular tools describing the world of nightclubs. People were categorised on the basis of their attitude towards the event, club, music, opposite sex and creating an acquaintance. In addition, respondents used stereotypes to describe nightclubs as well. These stereotypes are also used to identify a person’s position in the society. The preference of the club (and music style) helps to establish in- and out-groups. People identify themselves through opposing to the out-group, letting others know what they are not. It is very important that the in-group has a positive attitude towards the individual. The given thesis focuses mainly on people favouring the alternative music, future works should pay more attention to individuals favouring the popular music played in radio. How much they like meeting new people in clubs, do they identify themselves through nightclubs and what kind of stereotypes are far-spread. My work is just exploring the field of nightclubs. This research area should be given more attention in the future, because it has a significant part in young people’s lives

Kergemate liiklusväärtegude menetlemise lihtsustamise võimalused ja sellega kaasnevad riskid

http://www.ester.ee/record=b4577278*es

Liisinguandja kulutuste hüvitamise nõue - müügikahju ja -kasu jaotumine liisinguandja ja -võtja vahel

http://www.ester.ee/record=b4409452~S1*es

ÜRO Inimõiguste Nõukogu pädevus ja selle tegevusega seotud probleemid

http://tartu.ester.ee/record=b2658296~S1*es

Arengukava koostamine ja juhtkonna liikmete tõlgendused sellele üldhariduskooli näitel

http://www.ester.ee/record=b4501150*es

ORGANIZATIONAL CAPABILITIES FOR STRATEGIC LEADERSHIP IN WELL-KNOWN LOGISTICS COMPANIES IN FINLAND

This study focuses on organizational capabilities for strategic leadership in logistics companies in today’s hectic and dynamic business environment. The main aim of the thesis is to understand and to explore the logistics companies use organizational capabilities for strategic leadership and how they react to the changes. The mini-survey was made by analyzing seven well-known logistics companies in Finland. Organizational capabilities include formulating strategies, learning process, planning, making decisions, process developing and communication. Building these capabilities means to align personnel and organization to respond quickly and effectively to the changes, and to capitalize opportunities to turn them on successes. The main focus is on five key elements of strategic leadership: strategic orientation, translating strategy into action, aligning people and organization, determining effective strategic intervention points, and developing strategic competencies. The results show that the customers are very important to the companies and giving them high quality, expertise, cost-effective and profitable service is essential. Companies can practice strategic leadership when they have the capability to inspire people to successfully engage in a process of continuous change, performance enhancement, and implementation of organizational strategies. It involves flexibility and management with personnel. Listening, training and learning process will inspire people to participate in the process of change. Competitive advantages are the key elements which make the company’s business unique in the competitive market and attractive to the customers

6 –7aastaste koolieelikute kehaline aktiivsus Paide linna lasteaedades käivate laste näitel

http://www.ester.ee/record=b5150298*es