Politiikan tutkimuksen kritiikkiä ja rakentamista

Kirjallisuusarvostelu

Aistimuksellisuus, autoetnografia ja ruumiillinen tietäminen

Katsausartikkelit

Hallintolainkäytön tehostaminen

Kirjallisuusarvostelu

Kirja-arvio

Kirjallisuusarvostelu

New mechanisms regulating human Th1 and Th2 cell differentiation

Selective development of human T helper (Th) cells into functionally distinct Th1 and Th2 subtypes plays an essential role in the host immune response towards pathogens. However, abnormal function or differentiation of these cells can lead to development of various autoimmune diseases as well as asthma and allergy. Therefore, identification of key factors and the molecular mechanisms mediating Th1 and Th2 cell differentiation is important for understanding the molecular mechanisms of these diseases. The goal of this study was to identify novel factors involved in the regulation of Th1 and Th2 differentiation processes. A new method was optimized for enrichment of transiently transfected resting human primary T lymphocytes, that allowed the study of the influence of genes of interest in human Th1/Th2 cell differentiation and other primary Th cell functions. Functional characterization of PRELI, a novel activation-induced protein in human Th cells, identified it as a mitochondrial protein involved in the regulation of Th cell differentiation and apoptosis. By influencing the intracellular redox state, PRELI induces mitochondrial apoptosis pathway and downregulates STAT6 and Th2 differentiation. The data suggested that Calpain, an oxidative stress induced cysteine protease, is involved as a mediator in PRELI-induced downregulation of STAT6. PIM serine/threonine-specific kinases were identified as new regulators of human Th1 cell differentiation. PIM1 and PIM2 kinases were shown to be preferentially expressed in Th1 cells as compared to Th2 cells. RNA interference studies showed that PIM kinases enhance the production of IFN, the hallmark cytokine produced by Th1 cells. They also induce the expression of the key Th1-driving factor T-bet and the IL-12 signaling pathway during early phases of Th1 cell differentiation. Taken together, new regulators of human T helper cell differentiation were identified in this study, which provides new insights into the signaling mechanisms controlling the selective activation of human Th cell subsets.

Tuotekustannuslaskentamenetelmät eri tuotantomuodoissa

Lähtökohta työlle on John Fogelholmin vuonna 2001 julkaisema tutkimus tuotekustannuslaskentamenetelmien soveltuvuuksista eri tuotantoprosesseihin. Työn tavoitteena on tutkia, mitä uutta vuoden 2001 jälkeen aiheesta on kirjoitettu ja uudistaa näiden tietojen pohjalta Fogelholmin tutkimus nykypäivään. Aihetta lähdettiin tutkimaan laaja-alaisen kirjallisuuskatsauksen avulla, jossa tarkoituksena oli selvittää, mitkä tuotekustannuslaskentamenetelmistä ovat kaikkein eniten käytössä nykypäivän yrityksissä sekä millaisia ominaisuuksia yleisimmät tuotantoprosessit omaavat. Tämän jälkeen saatuja tuloksia sovellettiin käytäntöön erilaisten tutkimusten, artikkeleiden sekä omien päätelmien pohjalta tutkien, mitkä yleisimmistä tuotekustannuslaskentamenetelmistä sopivat parhaiten kuhunkin tuotantoprosessiin. Saatujen tulosten pohjalta rakennettiin yhteenvetotaulukko, josta voidaan havaita, mitä muutoksia aiheeseen liittyen on tapahtunut vajaan kymmenen vuoden aikana. Tutkimuksen tuloksista voidaan nähdä, että tuotantoprosessit jaotellaan nykyisin miltei samalla tavoin kuin aikaisemminkin, mutta laskentamenetelmissä on tapahtunut enemmän muutoksia modernin kustannuslaskennan käytön lisäännyttyä.

Conformational Regulation of alpha2beta1 Integrin in Ligand Binding

Integrins are heterodimeric cell adhesion receptors involved in cell-cell and cell-extracellular matrix (ECM) interactions. They transmit bidirectional signals across the cell membrane. This results in a wide range of biological events from cell differentiation to apoptosis. alpha2beta1 integrin is an abundant collagen receptor expressed on the surface of several cell types. In addition to ECM ligands, alpha2beta1 integrins are bound by echovirus 1 (EV1) which uses alpha2beta1 as a receptor to initiate its life cycle in the infected cell. The aim of this thesis project was to provide further insight into the mechanisms of alpha2beta1 integrin ligand recognition and receptor activation. Collagen fibrils are the principal tensile elements of the ECM. Yet, the interaction of alpha2beta1 integrin with the fibrillar form of collagen I has received relatively little attention. This research focused on the ability of alpha2beta1 integrin to act as a receptor for type I collagen fibrils. Also the molecular requirements of the EV1 interaction with alpha2beta1 were studied. Conventionally, ligand binding has been suggested to require integrin activation and the binding may further trigger integrin signalling. Another main objective of this study was to elucidate both the inside-out and outside-in signalling mechanisms of alpha2beta1 integrin in adherent cells. The results indicated that alpha2beta1 integrin is the principal integrin-type collagen receptor for type I collagen fibrils, and alpha2beta1 may participate in the regulation of pericellular collagen fibrillogenesis. Furthermore, alpha2beta1 integrin inside-out activation appeared to be synergistically regulated by integrin clustering and conformational activation. The triggering of alpha2beta1 integrin outside-in signalling, however, was shown to require both conformational changes and clustering. In contrast to ECM ligands, EV1 appeared to take advantage of the bent, inactive form of alpha2beta1 integrin in initiating its life cycle in the cell. This research together with other recent studies, has shed light on the molecular mechanisms of integrin activation. It is becoming evident that large ligands are able to bind to the bent form of integrin, which has been previously considered to be physiologically inactive. Consequently, our understanding of the conformational modulation of integrins upon activation is changing.