Raiskauksen maantieteestä

Kirjallisuusarvostelu

Tarvitaanko postformaalin ajattelun käsitettä?

S. 119-121: Liite 1: Bassechesin dialektisen ajattelun malli / Hanna-Maija Liitos. - S. 120: Taulukko 2. Dialektisen ajattelun skeemojen viitekehys (Basseches, 1984).

Toimijuudestako avaimet sukupuolilukkojen purkamiseen?

Kirjallisuusarvostelu

Factors Regulating Chondrogenic Differentiation

Chondrogenesis is a co-ordinated differentiation process in which mesenchymal cells condensate, differentiate into chondrocytes and begin to secrete molecules that form the extracellular matrix. It is regulated in a spatio-temporal manner by cellular interactions and growth and differentiation factors that modulate cellular signalling pathways and transcription of specific genes. Moreover, post-transcriptional regulation by microRNAs (miRNAs) has appeared to play a central role in diverse biological processes, but their role in skeletal development is not fully understood. Mesenchymal stromal cells (MSCs) are multipotent cells present in a variety of adult tissues, including bone marrow and adipose tissue. They can be isolated, expanded and, under defined conditions, induced to differentiate into multiple cell lineages including chondrocytes, osteoblasts and adipocytes in vitro and in vivo. Owing to their intrinsic capability to self-renew and differentiate into functional cell types, MSCs provide a promising source for cell-based therapeutic strategies for various degenerative diseases, such as osteoarthritis (OA). Due to the potential therapeutic applications, it is of importance to better understand the MSC biology and the regulatory mechanisms of their differentiation. In this study, an in vitro assay for chondrogenic differentiation of mouse MSCs (mMSCs) was developed for the screening of various factors for their chondrogenic potential. Conditions were optimized for pellet cultures by inducing mMSC with different bone morphogenetic proteins (BMPs) that were selected based on their known chondrogenic relevance. Characterization of the surface epitope profile, differentiation capacity and molecular signature of mMSCs illustrated the importance of cell population composition and the interaction between different populations in the cell fate determination and differentiation of MSCs. Regulation of Wnt signalling activity by Wnt antagonist sFRP-1 was elucidated as a potential modulator of lineage commitment. Delta-like 1 (dlk1), a factor regulating adipogenesis and osteogenesis, was shown to exhibit stage-specific expression during embryonic chondrogenesis and identified as a novel regulator of chondrogenesis, possibly through mediating the effect of TGF-beta1. Moreover, miRNA profiling demonstrated that MSCs differentiating into a certain lineage exhibit a specific miRNA expression profile. The complex regulatory network between miRNAs and transcription factors is suggested to play a crucial role in fine-tuning the differentiation of MSCs. These results demonstrate that commitment of mesenchymal stromal cells and further differentiation into specific lineages is regulated by interactions between MSCs, various growth and transcription factors, and miRNA-mediated translational repression of lineage-specific genes.

Marjatan laulu

Ensilevytys.

Crystallization characteristics of bioactive glasses

Bioactive glasses are excellent candidates for implant materials, because they can form a chemical bond to bone or guide bone growth, depending on the glass composition. Some compositions have even shown soft tissue attachment and antimicrobial effects. So far, most clinical applications are based on monoliths, plates and particulates of different grain sizes. There is a growing interest in special products such as porous implants sintered from microspheres and fibers drawn from preforms or glass melts. The viscosity range at which these are formed coincides with the crystallization temperature range for most bioactive glasses, thus complicating the manufacturing process. In this work, the crystallization tendency and its kinetics for a series of glasses with their compositions within the range of bioactivity were investigated. The factors affecting crystallization and how it is related to composition were studied by means of thermal analysis and hot stage microscopy. The crystal compositions formed during isothermal and non-isothermal heat treatments were analyzed with SEM-EDXA and X-ray diffraction analysis. The temperatures at which sintering and fiber drawing can take place without interfering with crystallization were determined and glass compositions which are suitable for these purposes were established. The bioactivity of glass fibers and partly crystallized glass plates was studied by soaking them in simulated body fluid (SBF). The thickness of silica, calcium and phosphate rich reaction layers on the glass surface after soaking was used as an indication of the bioactivity. The results indicated that the crystallization tendencies of the experimental glasses are strongly dependent on composition. The main factor affecting the crystallization was found to be the alkali oxide content: the higher the alkali oxide content the lower the crystallization temperature. The primary crystalline phase formed at low temperatures in these glasses was sodium calcium silicate. The crystals were found to form through internal nucleation, leading to bulk crystallization. These glasses had high bioactivity in vitro. Even when partially crystalline, they formed typical reaction layers, indicating bioactivity. In fact, sodium calcium silicate crystals were shown to transform in vitro into hydroxyapatite during soaking. However, crystallization should be avoided because it was shown to retard dissolution, bioactivity reactions and complicate fiber drawing process. Glass compositions having low alkali oxide content showed formation of wollastonite crystals on the surface, at about 300°C above the glass transition temperature. The wide range between glass transition and crystallization allowed viscous flow sintering of these compositions. These glasses also withstood the thermal treatments required for fiber drawing processing. Precipitation of calcium and phosphate on fibers of these glasses in SBF suggested that they were osteoconductive. Glasses showing bioactivity crystallize easily, making their hot working challenging. Undesired crystallization can be avoided by choosing suitable compositions and heat treatment parameters, allowing desired product forms to be attained. Small changes in the oxide composition of the glass can have large effects and therefore a thorough understanding of glass crystallization behavior is a necessity for a successful outcome, when designing and manufacturing implants containing bioactive glasses.

Dynamic interplay between the intermediate filament protein nestin and Cyclin-dependent kinase 5

Cellen har ett s.k. cytoskelett som bl.a. ger stadga åt cellen och deltar i dess form- och rörelsefunktioner. Intermediärfilamenten är en viktig del av cytoskelettet och de har länge varit kända för sina väsentliga roller i att upprätthålla den cellulära organisationen och vävnadernas integritet. På senare år har man insett att intermediärfilamenten har en större funktionell mångsidighet än man tidigare tänkts sig, i och med att en rad olika studier har visat betydelsen av intermediärfilamenten vid olika signaleringprocesser. Dessa proteinnätverk samverkar nämligen med kinaser och andra viktiga signalfaktorer och deltar därmed i cellens signaleringmaskineri. Intermediärfilamentproteinet nestin används ofta som en markör för stamceller men dess fysiologiska funktioner är i stort sett okända. Interaktion mellan nestin och ett signalkomplex bestående av cyklin-beroende kinas 5 (eng. Cyclin-dependent kinase, Cdk5) och dess aktivatorprotein p35 upptäcktes i vårt laboratorium före denna avhandling påbörjades. Därför var syftet med min avhandling att undersöka den funktionella betydelsen av nestin i regleringen av Cdk5/p35 komplexet. Cdk5 är ett multifunktionellt kinas som reglerar både utvecklingen och stressreaktioner i nerver och muskler. Vi visade att nestin skyddar neuronala stamceller under oxidativ stress genom dess förmåga att hämma Cdk5s skadliga aktivitet. Genom att förankra Cdk5/p35 komplexet, reglerar nestin den subcellulära lokaliseringen av Cdk5/p35 och minskar klyvningen av p35 till den mer stabila aktivatorn p25. Vi demonstrerade också aktiveringsmekanismen för Cdk5 under differentiering av muskelceller. Proteinkinas C zeta (PKCzeta) avslöjades ha en förmåga att accelera klyvningen av p35 till p25, och därmed öka aktiviteten hos Cdk5. Nestin kunde genom sin förmåga att reglera Cdk5 signalkomplexet styra muskelcellernas differentiering. Denna doktorsavhandling har på ett avgörande vis ökat förståelsen av de reglerande mekanismer som styr Cdk5 aktivering. Avhandling presenterar nestin och PKCzeta som kritiska faktorer i denna reglering. Vidare innehåller avhandlingen ny information om de cellulära funktionerna hos nestin som vi har visat vara en viktig reglerare av cellernas överlevnad och differentiering.