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  • Mikkola, Annamari (Helsingin yliopisto, 2018)
    Tutkimuksen kohteena on suomalainen suku, jossa esiintyy hampaiden kovakudosten perinnöllinen kehityshäiriö. Aikaisemmissa tutkimuksissa kehityshäiriön aiheuttava mutaatio on paikallistettu kromosomiin 15, ja kahden näytteen eksomisekvensoinnilla on löydetty useita mahdollisia mutaatioita. Tähän tutkimukseen on valittu näistä mutaatioista seitsemän tarkempaa tutkimista varten. Tutkittavaksi valitut mutaatiot sijaitsevat geeneissä OTUD7A, SPTBN5 (2 mutaatiota), PLA2G4F, FLJ27352, PRTG ja IGDCC4. Tarkoituksena on selvittää, esiintyvätkö ne kaikilla sairailla suvun jäsenillä ja voivatko ne olla kehityshäiriön taustalla. Aluksi tutkittavaksi valittiin neljä suvun jäsentä, joilla on todettu hampaiden kehityshäiriö. Heidän DNA-näytteilleen tehtiin polymeraasiketjureaktio (PCR), geelielektroforeesi ja sekvensointi. Kaksi etsityistä mutaatioista löytyi kaikilta näiltä henkilöiltä, ja ne sijaitsivat geeneissä IGDCC4 ja PRTG. Seuraavassa vaiheessa PRTG- ja IGDCC-geenien mutaatioita etsittiin laajemmalta joukolta suvun jäseniä. Tutkittavia näytteitä oli yhteensä 15. Näytteistä kahdeksan oli sairailta suvun jäseniltä, yksi oletetusti sairaalta ja kuusi terveiltä. Geenin IGDCC4 mutaatio löytyi kahdeksalta sairaalta heterotsygoottisena, mutta ei mahdollisesti sairaalta suvun jäseneltä. Lisäksi se löytyi yhdeltä terveeltä. Näin ollen tämä mutaatio ei ole kehityshäiriön taustalla. Geenin PRTG mutaatio löytyi kaikilta sairailta heterotsygoottisena eikä sitä löytynyt yhdeltäkään terveeltä, joten periaatteessa tämä voisi olla kehityshäiriön taustalla. Se aiheuttaa missense-mutaation, joka muuttaa valiinin leusiiniksi. Uusimpien tietokantojen mukaan sen yleisyys erityisesti Suomessa on kuitenkin jopa 0,015, joten on epätodennäköistä, että tämäkään mutaatio ainakaan yksin aiheuttaisi tutkimuksen kohteena olevan hampaiden kovakudosten kehityshäiriön. Tutkimuksen kohteena olevan kehityshäiriön aiheuttavan mutaation selvittämiseksi tarvitaan siis jatkotutkimuksia. (217 sanaa)
  • Virkunen, Ekaterina (Helsingin yliopisto, 2018)
    Tiivistelmä Referat – Abstract The majority of cancers, such as breast cancer, originate from epithelial structures. Highly organized epithelial tissues are comprised of cells which manifest apico-basal polarization. Factors regulating apico-basal polarity and epithelial integrity are often observed deregulated in cancer cells and loss of polarity is often observed in tumors. However, the importance and the specific role of epithelial integrity regulators in tumorigenesis are still not fully defined. This study shows that the key regulators of epithelial cell polarity Par6B and Par6G proteins have a role in the restriction of cell proliferation in mammary epithelial cell lines. Using the shRNA silencing approach, downregulation of PARD6B and PARD6G in the cells lead to the impediment of the cell-cycle exit, verified in proliferation suppressive conditions in which cells normally would enter quiescence. Par6 proteins were shown to regulate cell proliferation via the canonical PI3K/Akt pathway, which is one of the most commonly deregulated cell proliferation promoting pathways in cancer cells. The results demonstrate the unknown function of Par6B and Par6G proteins as cell proliferation regulators and a previously unrecognized relation between Par6 proteins and PI3K/Akt pathway. However, the detailed interaction between Par6 proteins and the PI3K/Akt pathway ought to be investigated further. In addition, the results revealed that Par6 proteins have different effects on cell proliferation suggesting biological differences between Par6 proteins and that certainly bears further investigation. In conclusion, the study presents a previously unknown connection between epithelial integrity regulators and cancer-relevant cell proliferation promoting pathways, which may provide new targets for therapeutic intervention in the future.
  • Nakane, Elina (Helsingin yliopisto, 2018)
    Tavoitteet. Äidin diabetes on yhteydessä raskaudenaikaisiin komplikaatioihin, mutta äidin diabeteksen vaikutusta jälkeläisten kognitioon ei ole tutkittu yhtä laajasti. Aiemmissa tutkimuksissa äidin diabetes on yhdistetty pääsääntöisesti alle kouluikäisten lasten hieman heikentyneeseen yleiseen kognitiiviseen ja kielelliseen tasoon. On kuitenkin vielä epäselvää, että vaikuttaako äidin diabetes itsessään lapsen, ja myöhemmin aikuisen jälkeläisen, kognitiiviseen tasoon. Lapset, joilla on ollut myös muita samanaikaisia kehityksellisiä riskitekijöitä, vaikuttaisivat olevan alttiita äidin diabeteksen negatiivisille vaikutuksille, toisin kuin lapset, joilla riskitekijöitä ei ole ollut. Tämän tutkimuksen tarkoituksena oli tutkia, onko äidin diabetes yhteydessä jälkeläisten yleiseen kognitiiviseen tasoon lapsuudessa ja keski-iän alussa, kun jälkeläisillä joko oli tai ei ollut muita syntymänaikaisia riskitekijöitä. Hypoteesina oli, että vain jälkeläisillä, joilla oli todettu äidin diabeteksen lisäksi myös muita syntymäaikaisia riskitekijöitä, yleinen kognitiivinen taso olisi madaltunut. Tavoitteena oli myös selvittää, että muuttuuko kummankaan riskiryhmän yleinen kognitiivinen taso ajan myötä. Menetelmät. Tämä tutkimus on osa prospektiivista syntymäkohorttitutkimusta, jossa tutkitaan syntymäaikaisten riskitekijöiden pitkittäisvaikutusta. Vuosina 1971–1974 Kätilöopiston perättäisistä synnytyksistä (n=22359), 93:lla vastasyntyneellä todettiin äidin diabetes raskauden aikana tai ennen sitä. Osalla vastasyntyneistä ennalta määriteltynä riskitekijänä oli pelkästään äidin diabetes (n=59), kun osalla vastasyntyneistä ilmeni useita syntymäaikaisia riskejä (n=34). Tutkimukseen osallistuneiden jälkeläisten ja kontrolliryhmän yleinen kognitiivinen taso arvioitiin 9 ja 40 vuoden iässä Wechslerin älykkyystesteillä osana laajempaa neuropsykologista seurantatutkimusta. Ryhmien välisiä eroja tarkasteltiin ryhmä- ja parivertailuilla. Mittausten välistä muutosta tutkittiin ryhmittäin lineaarisilla monitasomalleilla. Tulokset ja johtopäätökset. Tutkimuksen tulokset eivät tukeneet asetettua hypoteesia: Molemmilla riskiryhmillä, riippumatta muiden syntymäaikaisten riskien ilmenemisestä, yleinen kognitiivinen ja kielellinen taso olivat hieman kontrolleja heikompia. Keski-iän alussa ryhmien välillä ei ilmennyt eroja yleisessä kognitiivisessa tasossa. Vaikuttaisi siltä, että ainakin yleisen kognitiivisen tason ja opittujen kielellisten taitojen osalta usean riskitekijän ryhmässä taidot olivat parantuneet. Muuten suoriutuminen pysyi ryhmittäin melko samana.
  • Holma, Juho Mikael (Helsingin yliopisto, 2018)
    Välikorvatulehdus on tavallinen yleensä ylähengitystieinfektion jälkitilana kehittyvä sairaus.Tavallisesti välikorvatulehdus paranee konservatiivisella hoidolla, mutta komplikaatioiden kehittyessä tarvitaan myös korvakirurgisia toimenpiteitä. Komplikaatioita esiintyy edelleen myös länsimaissa,mutta erityisen runsaasti maissa, joissa terveydenhuolto on vähemmän kehittynyt. Tässä tutkimuksessa käytiin läpi vuosina 2007-2016 HYKS Korvaklinikassa korvatulehdusten vuoksi korvakirurgisesti hoidetut potilaat (poislukien pelkkä tärykalvoputkitus). Tavoitteena oli kuvata korvatulehdusten kirurgisen hoidon nykytila HUS-alueella koskien mm. toimenpidediagnooseja, toimenpidemäärää kokonaisuutena, eri toimenpiteiden suhteellisia määriä, potilaiden ikäjakaumaa sekä syntyperää. Toimenpiteet jaoteltiin vuosittain taulukoihin, jolloin eri muuttujien kehitystä pystyttiin arvioimaan ajan funktiona. Tutkimuksessa kävi ilmi, että seuranta-ajalla leikkausten vuosittainen kokonaismäärä (noin 30-40 operaatiota) on pysynyt jotakuinkin vakiona. Akuutti ja krooninen mastoidiitti olivat odotetusti yleisimmät toimenpidediagnoosit. 90 % leikkauksista tehtiin korvantausviillosta mastoidin kautta. Eri toimenpiteiden suhteellisissa osuuksissa tapahtui tiettyjä muutoksia, jotka selittyvät lähinnä kirjaamiskäytäntöjen muuttumisella. Korvakirurgista leikkausta vaatineista potilaista suurin osa oli iältään 31 ja 70 ikävuoden välillä. Seuranta-ajan alkuvuosina leikatuista potilaista noin 15-20 prosenttia oli taustaltaan ei-kantasuomalaisia, kun taas viimeisimpinä seurantajakson vuosina tämä osuus oli noussut korkeimmillaan yli 40 prosenttiin. Vaikka korvatulehdusten hoito on nykyään tehokasta ja komplikaatiot melko harvinaisia, ei korvakirurgisten toimenpiteiden tarve HUS-alueella ole vähenemässä. (180 sanaa)
  • Kleine, Iida-Marja (Helsingin yliopisto, 2018)
    This study investigates the metabolic consequences of a biomarker for mitochondrial myopathies, using the mouse as a model organism. The studied biomarker is fibroblast growth factor 21 (FGF21), which is secreted in high amounts from the diseased muscle tissue. It is an endocrine hormone that regulates lipid metabolism, and in healthy individuals it is mainly secreted from the liver. I utilized skeletal muscle samples from mice that were either wild type or had a mitochondrial myopathy, both with or without a whole-body knockout of FGF21. I analysed a data set from a targeted metabolomic experiment conducted on the skeletal muscle samples. The experiment was performed by our collaborator Vidya Velagapudi. Additionally I measured protein and mRNA expression of selected enzymes from the muscle samples. This study shows, that the cytokine FGF21 contributes to the disease progression of mitochondrial myopathy. The aspects of pathophysiology it regulates were all found to center on the metabolic pathway of one carbon (1C) metabolism. Serine de novo synthesis shuttles glucose carbons into 1C metabolism. The transsulfuration pathway produces glutathione using carbon units from the 1C pathway. The results of this study show, that FGF21 mediates the upregulation of alternative carbon donors in one carbon metabolism, especially serine biosynthesis, and the elevated utilisation of carbon units in the transsulfuration pathway. Not all of the metabolic changes characteristic of mitochondrial myopathy were affected by FGF21, e.g. the upregulation of acyl carnitines seen in mitochondrial myopathy was not affected by the knock-out of FGF21.
  • Geier, Anna (Helsingin yliopisto, 2018)
    Objectives. On the basis of previous research, working memory and many other cognitive abilities are associated with mathematical skills. By evaluating working memory and other cognitive skills, it might be possible to predict, which children will have problems in learning mathematics. Especially in kindergarten proper assessment methods are needed, with which the working memory and other cognitive abilities of children could be evaluated. In this research we examined, what kind of relationship do tasks that assess working memory, flexible intelligence, Working Memory Rating Scale and Taitokysely have with early mathematical skills. In addition, the objective of this study was to evaluate whether questionnaires can produce similar knowledge, as tasks that evaluate working memory. Methods. This study is part of joint research project of the universities of Turku and Helsinki, the Early Rehearsal of Working Memory. The children who participated in the study were 6-7 years old (n=50). The working memory was assessed with AWMA tasks, and mathematical skills were assessed with lukujonotaidot- and Banuca tests. Flexible intelligence was assessed with Raven’s matrices. The kindergarten teachers completed a Working Memory Rating Scale (WMRS) and a Taitokysely of each child. The associations between the variables were assessed with correlation coefficients, linear regression analysis and regression commonality analysis. Results and Conclusions. WMRS, Taitokysely and part of the tasks, that were used to evaluate working memory were associated with mathematical skills. Most of the explained variance is common to the predictors, but the WMRS and the tasks that were used to evaluate passive visuospatial working memory were the best individual predictors. On the basis of this research, especially these methods would be good when evaluating children’s working memory, problems of working memory and mathematical skills. Questionnaires and tasks were both able to produce knowledge about working memory and mathematics.
  • Bergman, Matilda (Helsingin yliopisto, 2018)
    Purpose Childhood maltreatment is a significant risk factor for the development of mental disorders. Previous studies have shown that maltreatment is associated to generalized anxiety disorder (GAD), which impairs work capacity and social functioning, thus causing costs for the individual and society. However, the research concerning the effects of different kind of maltreatment experiences on and the pathways to GAD is scarce. Among the factors that predispose individual to anxiety disorders is a low sense of control, which also has been associated to childhood maltreatment. To date, sense of control has not been examined as a possible mediator or moderator of the relationship between maltreatment and GAD. This study aimed to examine the relationships of childhood physical and emotional maltreatment, the frequency, amount and perpetrator of maltreatment, and sense of control with GAD in adulthood. Additionally, the aim was to test sense of control as a possible mediator or moderator. Methods The data was derived from a large (n=5856) Midlife Development in the United States (MIDUS) -study. Childhood physical and emotional maltreatment was measured with Conflict Tactics Scales, the symptoms of GAD was measured with the World Health Organization’s (WHO) Composite International Diagnostic Interview Short-Form (CIDI-SF), and sense of control was measured with a questionnaire composing of two scales, personal mastery and perceived constrains. Questionnaires and telephone interviews were used for data collection. Data analyses were conducted by logistic and linear regression analysis and analysis of covariance. Mediation effects were tested by using bootstrapping method. Results and conclusions The amount, type and frequency of child maltreatment were associated with the symptoms of GAD in adulthood. The risk formed by different kind of experiences of child maltreatment was associated with the sex of the respondent and whether the perpetrator was a sibling or a parent. Further, sense of control mediated the effect from child maltreatment to GAD. The results highlight the importance of early detection and intervention of maltreatment and enhancing sense of control in order to prevent GAD.
  • Seppälä, Metti (Helsingin yliopisto, 2018)
    Tavoitteet. Kaksikielisyydellä voi olla yhtäältä positiivisia, toisaalta negatiivisia vaikutuksia fonologian kehitykseen. Myös kielihäiriö saattaa aiheuttaa erityisiä haasteita fonologian osa-alueella. Tämän tutkimuksen tarkoituksena oli verrata peräkkäisesti kaksikielisten kielihäiriöisten sekä yksikielisten kielihäiriöisten lasten paradigmaattisia ja fonotaktisia taitoja suomen kielessä. Tutkimuksessa selvitettiin myös onko kaksi- ja yksikielisten kielihäiriöisten lasten paradigmaattisten ja fonotaktisten taitojen välillä yhteyttä. Lisäksi tutkittiin selittävätkö kaksikielisten kielihäiriöisten lasten sukupuoli, ikä ja suomen kielen altistuksen kesto ja yksikielisten kielihäiriöisten lasten sukupuoli ja ikä lasten fonotaktisia taitoja. Menetelmät. Tutkittavina oli 3;5–5;10-vuotiaita kaksikielisiä kielihäiriöisiä lapsia (N = 46), joiden taitoja verrattiin 3;5–5;9-vuotiaiden yksikielisten kielihäiriöisten lasten (N = 46) taitoihin. Lapset oli rekrytoitu Helsingin pitkittäiseen SLI-tutkimukseen vuosina 2013–2015. Tutkimusmenetelmänä oli Fonologiatesti. Ryhmien suoriutumista paradigmaattisissa ja fonotaktisissa taidoissa vertailtiin tilastollisin menetelmin. Paradigmaattisten ja fonotaktisten taitojen yhteyttä tutkittiin erikseen kummassakin ryhmässä korrelaatiokertoimella. Kaksikielisten lasten ryhmässä tutkittiin fonotaktisten taitojen riippuvuutta sukupuolesta, iästä ja suomen kielen altistuksen kestosta. Yksikielisten lasten ryhmässä tutkittiin fonotaktisten taitojen riippuvuutta sukupuolesta ja iästä. Tulokset ja johtopäätökset. Kaksikieliset kielihäiriöiset lapset hallitsivat suomen kielen paradigmaattiset ja fonotaktiset taidot paremmin kuin yksikieliset kielihäiriöiset lapset. Paradigmaattiset ja fonotaktiset taidot korreloivat vahvasti kummassakin ryhmässä. Korrelaatiot olivat tilastollisesti merkitsevämpiä yksikielisten kielihäiriöisten lasten aineistossa. Ikä oli tilastollisesti merkitsevä fonotaktisia taitoja selittävä muuttuja. Kaksikielisten kielihäiriöisten lasten suomen kielen altistuksen kesto ei ollut tilastollisesti merkitsevä fonotaktisia taitoja selittävä muuttuja. Kaksikieliset kielihäiriöiset lapset saattavat puhua selkeämmin kuin yksikieliset kielihäiriöiset lapset. Kaksikielisyys saattaa toimia suojaavana tekijänä kielihäiriöön liittyvissä fonologisissa vaikeuksissa.
  • Järviö, Heini (Helsingin yliopisto, 2018)
    Objectives. Even over one third of information security breaches are caused by human actions, which makes knowing the factors behind information security behaviour especially important in today’s world. The objective of this study was to investigate what kind of individual and organisational factors affect the way we act with personal and organisational data. The research model of this study combined the Theory of Reasoned Action (TRA) and personality traits as predictors of information security behaviour. In TRA, the best predictor of an action is the intention to do it, which in turn is affected by the attitude towards the action and subjective norms. Scenario method was used to investigate if TRA predicts actions also in concrete scenarios The included personality theories were Big Five and Dark Triad theories, of which the latter has not yet been studied in information security research. Methods. The data in this study was a sample of the students in the University of Helsinki and the National Defence University (N=408). The participants completed a survey which measured personality traits and the elements of TRA. Personality was assessed with Short Five and Short Dark Triad inventories. In addition, the participants read three scenarios where information security was at risk. After this they rated their probability to act in a similar way (intention) and their evaluation of the presented act (attitude). The scenarios in this study where divided in three groups according to their level of risk and each participant received scenarios only from a same level. The relationship between personality traits and responses in scenario situations was assessed with regression analysis. The measurement model was assessed with path analysis. Results and conclusions. The measurement model fit the data when it was used to predict security attitudes and the harm presented in the scenarios was mild. The TRA structure was therefore found to predict attitudes in concrete situations as well. The relationship between personality traits and scenario responses was different for intentions and attitudes. Higher scores in two Dark Triad traits were linked to higher intentions. Higher extroversion predicted both lower intentions and attitudes. In addition, higher openness was linked to more positive attitudes, and these two connections remained in the measurement model. This study provided more information about the relationship between personality traits and information security behaviour and gave insight on which factors to improve to secure information in organisations.
  • Taskinen, Miisa (Helsingin yliopisto, 2018)
    Arvot ovat elämää ohjaavia tavoitteita, joiden on todettu olevan yhteydessä useisiin erilaisiin muuttujiin, ja niillä on ennustettu mielekkäästi monenlaista käyttäytymistä. Schwartzin arvoteoriasta on tullut arvotutkimuksen valtavirtaa, ja se on saanut mittavaa tukea maailmanlaajuisesti. Ottaen huomioon, kuinka keskeinen asema arvoilla on ihmisten elämässä, on arvotutkimusta kuitenkin tehty suhteellisen vähän. Yksi syy siihen saattaa olla yleisimmin käytettyjen arvomittareiden pituus. Täten on tarvetta lyhyelle mittarille, joka voidaan lisätä laajojenkin tutkimuksien yhteyteen. Short Schwartz’s Value Surveylla (SSVS) on alustavaa näyttöä hyvästä reliabiliteetista ja validiteetista, mutta tämän tutkimuksen tarkoitus on uudelleenvalidoida SSVS edustavalla otoksella, määrittää sille suomalaiset normit ja tarjota uutta tutkimustietoa arvojen ja muiden muuttujien, tässä tapauksessa koetun rikollisuuden määrän, yhteydestä. Tutkimuksen aineisto on kansallisesti edustava otos, ja se koostui 1245:stä 18-87 -vuotiaasta henkilöstä. Tuloksia verrattiin European Social Survey 7 -aineistoon, joka on niin ikään kansallisesti edustava otos, mutta jossa arvoja mitataan pidemmällä arvomittarilla, Portrait Values Questionnairella (PVQ-21). Faktorianalyysilla löydettiin SSVS:n arvorakenteesta teorian mukainen kaksiulotteinen malli, joka koostui itsensä ylittämisen ja säilyttämisen arvoulottuvuuksista. Lisäksi arvotyyppien arvorakenne vastasi pääosin Schwartzin teoriaa. SSVS:llä mitatut arvot olivat myös yhteydessä useisiin validiteettikriteereihin, joita odotettiin aiempien tutkimuksien perusteella, ja yhteydet olivat samanlaisia kuin PVQ-21:llä. Lopuksi esitettiin vielä uutta tietoa arvojen yhteyksistä: molemmat arvoulottuvuudet vaikuttivat koettuun rikollisuuden määrän kasvuun. Arvoulottuvuuksille lasketut painokertoimet ja normit mahdollistavat vastaisuudessa tuloksien vertailun sekä yksilö- että ryhmätasolla. Tutkimuksen perusteella tutkijat voivat jatkossa entistä luottavaisemmin mielin integroida arvot osaksi myös sellaisia tutkimuksia, joissa ei ole mahdollista käyttää normaalimittaisia kyselyitä.
  • Tuohinto, Krista (Helsingin yliopisto, 2018)
    Kaposi’s sarcoma herpesvirus (KSHV), also called human herpesvirus 8 (HHV-8), was discovered following the AIDS-epidemic as the causative agent of Kaposi’s sarcoma (KS), an angiogenic endothelial tumor of the skin, and of two rare lymphoproliferative diseases, primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). Infection by KSHV displays two life cycle phases; latent and lytic replication. In latency, the virus stays dormant within the host, expressing only a few genes and no viral particles are produced. Latency is the default mode of infection, however, upon appropriate induction the virus reactivates to express all of its genes and replicate viral DNA during the productive lytic replication, culminating with the release of infectious progeny particles and lysis of the host cells. Virus reactivation from latency to the lytic replication is an essential step in the KS pathogenesis. Upon KSHV infection, endothelial cells (EC) undergo reprogramming towards spindle cell, the principal proliferating cell in advanced KS lesions. The transcription factor prospero related homeobox gene Prox1 has an important role in mediating the effects of KSHV on EC reprogramming, contributing to the KS development. Prox1 is the master regulator of lymphatic endothelial cell fate, and its expression is manipulated during the KSHV infection. However, the role of Prox1 in the KSHV life cycle and lytic reactivation has not been studied. To elucidate the role of Prox1 in KSHV reactivation from latency, the effect of ectopic expression of Prox1 on the lytic gene and protein expression in both latent and reactivated KSHV-infected cells was studied. This led to a significant increase in KSHV lytic gene and protein expression, suggesting Prox1 as a positive regulator of KSHV lytic replication. Moreover, Prox1 wild-type, but not its DNA-binding deficient mutant, could significantly increase the release of infectious virions. To investigate the expression levels of Prox1 during KSHV infection, infection kinetics assay was performed, which showed an increase in the Prox1 levels during acute infection. Intriguingly, this was followed by a progressive decrease in the Prox1 levels as latency was established. In conclusion, the focus of this thesis is to investigate the role of Prox1 in KSHV reactivation, and to provide a deeper insight into the virus reactivation mechanisms that can be utilized for future therapeutic strategies against KSHV-mediated tumorigenesis of KS. Keywords: KSHV, Kaposi’s sarcoma, Prox1, virus reactivation, lytic replication
  • Ginström, Laura (Helsingin yliopisto, 2018)
    Objective. Non-communicable diseases related to obesity, physical inactivity and poor fitness are widespread public health concerns. Research has shown that personality traits, especially neuroticism and conscientiousness, are linked to health outcomes. The positive effect of music on health has also been the topic of recent research. The aim of this study is to examine if and how five-factor-model personality traits and use of music are related to risk factors of non-communicable diseases. Methods. Participants were men and women (n=37) aged between 19 and 40 who took part in MoMaMo! intervention study. Their physical activity, personality and use of music were assessed by questionnaires. Participants went through a cardiopulmonary exercise test and their body composition and blood samples were analysed. Logistic regression and a mediation analysis were used to examine relationships between personality, use of music and the risk factors. Results and discussion. Although the participants were obese and their fitness level was poor, they reported very high levels of physical activity. Openness to experience was the only trait which was associated with higher BMI and body fat. Use of music was associated with higher body fat and lower cardiorespiratory fitness. Mediation analysis revealed that openness to experience was positively related to use of music and this predicted lower levels of fitness. It is possible that open individuals prefer music-related hobbies over exercising and sports. The questionnaire “Brief Music in Mood Regulation” might also measure some other tendencies which are related to poor fitness. The aim of future studies should be examining these relationships in a community sample and assessing the mechanisms underlying them.
  • Godbole, Nimish (Helsingin yliopisto, 2018)
    Background: Malignant mesothelioma is a fatal cancer of the mesothelial cells characterized by previous exposure to asbestos, long latency period and shorter survival time thereafter. Lack of highly sensitive and specific biomarkers and no curative treatment at present has made the continuous study of mesothelioma important. One of the biomarker under study are the microRNAs (miRNAs) which are small non-coding RNAs of about 20-22 nucleotides long which regulate post-translational gene expression. MiRNAs control several essential biological pathways including the epithelial-mesenchymal transition (EMT) pathway. Their dysregulation can lead to disruption of these pathways and also to the development of cancer. Identifying and understanding the role played by these miRNAs in malignant mesothelioma will help in their development as an effective diagnostic, prognostic and therapeutic target for this cancer. Aims: The study aims to first identify miRNAs previously linked with malignant mesothelioma, invasion and the EMT pathway based on review of literature. The study then aims to characterize miRNAs expression in established mesothelial cell lines used widely in mesothelioma research. Material & methods: Literature review is conducted using peer reviewed articles and limiting the articles published within the last 5 years. For characterizing the miRNAs, 6 mesothelial cell lines are used of which one is non-tumorigenic and used to represent a healthy control. Small RNA sequencing is done of all 6 cell lines and results analyzed using the Chipster analysis software. Results: A comprehensive list of 100 miRNAs was created which were linked to malignant mesothelioma, invasion, metastasis and EMT pathway. Small RNA sequencing of the cell lines revealed 134 miRNAs which were expressed in at least one of the cell lines. 34 of these miRNAs had higher counts in the healthy control as compared to all the cancer cell lines. In addition, we found 19 miRNAs having low counts in the control cell line but showed downregulation to zero in all the cancer cell lines. 4 miRNAs, namely miR-10a-5p, miR- 21-5p, miR-23b-3p and miR-183-5p, were also found in this study which were not previously linked with malignant mesothelioma. Conclusion: Characterization of the available mesothelial cell lines is the first step in understanding the role played by miRNAs in the development of this cancer. Further studies are needed to confirm the entire list of mesothelioma associated miRNAs found here, especially the 4 miRNAs which were not previously linked to mesothelioma. Validation of the miRNAs through comparison with patient samples with higher number of biological replicates and greater depth of libraries along with miRNA pathway analysis will help the development of miRNAs as a diagnostic and prognostic marker for this cancer.
  • Pörsti, Elina (Helsingin yliopisto, 2018)
    The capability to generate human induced pluripotent stem cells (iPSC) from somatic cells provides remarkable possibilities for regenerative medicine. However, prior to clinical applications the process of reprogramming should be optimized and carefully characterized. The purpose of this study was to get insight in reprogramming of human somatic cells to pluripotency using CRISPR-dCas9 activator system (CRISPRa). CRISPRa is a RNA guided bacterial nuclease system that has been modified for gene expression control. The study had two subprojects. The aims of the first subproject were 1) to reprogram hNESCs to pluripotency with CRISPRa in 2D culture, 2) to determine the efficacy of reprogramming and 3) to study whether CRISPRa-mediated pluripotent reprogramming pathway involves a mesendoderm-resembling intermediate state. The aim of the second subproject was to explore the possibility of CRISPRa-mediated endogenous gene activation and reprogramming to pluripotency also in 3D cell cultures. I performed the reprogramming in 2D and 3D cell cultures by using a dCas9 activator to induce different combinations of endogenous pluripotency reprogramming factors OCT4 (octamer-binding transcription factor 4), SOX2 (Sex determining region Y-box 2), NANOG, c-MYC, KLF4 (Krüppel-like factor 4) and LIN28. I analysed the results of the reprogramming at protein level, using alkaline phosphatase staining and immunocytochemistry, and at mRNA level, using qRT-PCR. The 2D reprogramming served as a proof-of-principle for reprogramming with CRISPRa. This study shows, that CRISPRa can be used to reprogram human neural stem cells to iPSC with different combinations of pluripotency reprogramming factors or by inducing a single master-regulator gene, OCT4. In addition, the reprogramming process was very efficient. I did not detect mesendodermal intermediate state in CRISPRa-mediated reprogramming to pluripotency, in contrast to published results from transgene- and small molecules-based reprogramming studies. Thus, this result suggests that the pathway leading to pluripotency differs between CRISPRa-mediated reprogramming and the two other reprogramming methods. CRISPRa can be used to initiate reprogramming also in 3D cell culture. However, in 3D cell culture the cells were not fully reprogrammed. Based on these findings, I postulate that CRISPRa serves as an alternative method for generating human iPSC. In addition, CRISPRa can be further developed into a platform for direct reprogramming of organoids for in vitro disease modelling in 3D.
  • Tappura, Hanna (Helsingin yliopisto, 2018)
    Aim: Due to the plasticity of the brain of a child under three years old early intervention can be very effective and affect the growth and development of the child extensively. As a concept early intervention is as yet unestablished within our healthcare system. The purpose of this study was to find out what kind of experiences Finnish speech-language therapists (SLTs) have about the assessment and the rehabilitation of children under three years old and the readiness of SLTs to work with these small children. The study also aimed to find out the reasons why small children are being sent to speech-language therapists. Methods: This study was done by a questionnaire and the material was gathered using an electrical survey with the E-lomake -program of the University of Helsinki between April and May 2016. The questionnaire was delivered to Finnish SLTs via the Finnish Assocation of Speech Therapists and four corporations that employ SLTs. The data was analysed with the IBM SPSS Statistics 24 -program using nonparameterized statistical tests and qualitative grouping. Results and conclusions: The questionnaire was answered by 194 SLTs out of which 111 worked regulary and 73 occasionally with children under three. The SLTs’ know-how about working with small children was mostly based on work experience. The professional capabilities were maintained and developed by additional trainings and literature. A degree in logopedics was considered to provide only minor capabilities toward working with small children. The results indicate that small children are sent to SLTs mostly because of disabilities and delayed speech development. The most popular assessment methods were tests, free observation and interviewing the child’s parents. AAC methods and playing were popular methods of rehabilitation. The practices in rehabilitating small children were varying and based on the available resources. According to the SLTs other healthcare professionals are not aware of what an SLT does and therefore their know-how is not utilized to it’s full extent.