”Sen kuuluu sen lapsen nähä, että vedetään yhtä köyttä.”:vanhempien käsityksiä kasvatusyhteistyön merkityksestä lapsen itsetunnon rakentumiselle esi- ja alkuopetuksen nivelvaiheessa

Tiivistelmä. Itsetunto voidaan nähdä ihmisen kykynä luottaa itseensä, pitää itsestään ja arvostaa itseään heikkouksistaan huolimatta. Alle 6-vuotiaan lapsen minäkuva ja itsetunto muodostuvat kodin kokemusmaailmassa. Kouluun siirtyessään lapsen elinpiiri laajenee, ja itsetuntoon vaikuttavat vanhempien lisäksi myös opettajat, koulutoverit ja koulun toimintakulttuuri. Kasvatusyhteistyön tehtävänä on edistää lapsen tervettä kasvua ja kehitystä sekä lisätä hänen hyvinvointia ja turvallisuutta, mutta millainen rooli opettajan ja vanhempien välisellä yhteistyöllä on lapsen rakentaessa vahvaa itsetuntoa sekä minäkuvaansa koululaisena? Tutkielman teoreettinen viitekehys esittelee itsetunnon ja minäkuvan rakentumisen teorioita sekä kasvatusyhteistyötä käsitteleviä tutkimuksia ja yhteistyötä ohjaavia asetuksia. Näiden pohjalta tarkastelemme kodin ja koulun kasvatusvastuun jakautumista sekä lapsen itsetunnon ja minäkuvan muovautumista yhteistyön keskiössä. Tutkimuksen tavoitteena on selvittää vanhempien käsityksiä ja kokemuksia opettajan kanssa tehdyn kasvatusyhteistyön vaikutuksista lapsen itsetunnon rakentumiseen esi- ja alkuopetuksen nivelvaiheessa. Tutkimus on toteutettu fenomenografisella otteella ja sisällönanalyysin keinoin. Aineisto on tuotettu teoriasidonnaisella teemahaastattelulla marras–joulukuussa 2019. Haastateltavina oli neljä ensimmäisen luokan aloittaneen lapsen vanhempaa eri puolilta Suomea. Tutkimukseen osallistuneet vanhemmat katsoivat lapsen minäkuvan ja itsetunnon kokevan muutoksia kouluun siirtymisen ja koululaisen rooliin kasvamisen myötä. Tutkimus toteaa kasvatusyhteistyön näyttäytyvän vanhemmille ensisijaisesti molemminpuolisena käytännön tiedottamisena ja lapsen oppimiseen painottuvien asioiden jakamisena. Kuitenkin kasvatusyhteistyössä jaetun tiedon ja yhdessä tapahtuvan arvioinnin sekä yhteistyön mahdollistaman kasvatuksellisen tuen myötä vanhemmat ja opettaja rakentavat jaettua näkemystä lapsesta. Tämä jaettu näkemys mahdollistaa lapselle turvallisuuden tunteen, jonka pohjalta lapsen itsetunto voi kehittyä vahvaksi. Tutkielma vahvistaa itsetunnon asemaa tärkeänä kasvatusyhteistyön teemana.“The child must see that we’re pulling together.” : parents’ perceptions of the importance of family-school partnership in the development of the child’s self-esteem during the preschoolschool transition and the first year of primary education. Abstract. Self-esteem can be seen as an individual’s ability to trust, like and appreciate oneself despite their weaknesses. The self-image and self-esteem of a child under the age of six are shaped by the experiences at home. As a child enters school, the child’s circle of life expands and his or her self-esteem is influenced not only by parents, but also by teachers, schoolmates and the school’s operating culture. The purpose of home-school co-operation is to promote the healthy growth and development of the child and to increase his or her well-being and safety, but what role does family-school partnership play in the construction of the child’s self-image as a pupil? The theoretical framework of the thesis introduces theories of self-esteem and self-image development, as well as research on home-school co-operation. On the basis of these, we examine the shared responsibilities of families and schools and the child’s development of self-esteem and self-image at the centre of these overlapping influences. The purpose of this study is to explore parents’ perceptions and experiences of the impact of the co-operation with the classroom teacher on their child’s self-esteem during the preschool-school transition. The research has been carried out with a phenomenographic approach and by means of content analysis. The material was produced by a theory-based theme interview in November–December 2019. Four parents of first-graders from around Finland were interviewed. The parents considered their child’s self-image and self-esteem to go through changes as their child started school and began growing into the role of a pupil. The study concludes that home-school co-operation appears to parents primarily as sharing of information on practical matters and the child’s learning. However, through shared knowledge and joint assessment, and the educational support the collaboration provides, parents and teacher are building a shared view of the child. This shared view between parents and teacher enables the child to feel a sense of security, on the basis of which his or her self-esteem can develop to be strong. The thesis strengthens the position of self-esteem as an important theme of family-school partnership

Early DNA methylation changes in children developing beta cell autoimmunity at a young age

Aims/hypothesis Type 1 diabetes is a chronic autoimmune disease of complex aetiology, including a potential role for epigenetic regulation. Previous epigenomic studies focused mainly on clinically diagnosed individuals. The aim of the study was to assess early DNA methylation changes associated with type 1 diabetes already before the diagnosis or even before the appearance of autoantibodies. Methods Reduced representation bisulphite sequencing (RRBS) was applied to study DNA methylation in purified CD4(+) T cell, CD8(+) T cell and CD4(-)CD8(-) cell fractions of 226 peripheral blood mononuclear cell samples longitudinally collected from seven type 1 diabetes-specific autoantibody-positive individuals and control individuals matched for age, sex, HLA risk and place of birth. We also explored correlations between DNA methylation and gene expression using RNA sequencing data from the same samples. Technical validation of RRBS results was performed using pyrosequencing. Results We identified 79, 56 and 45 differentially methylated regions in CD4(+) T cells, CD8(+) T cells and CD4-CD8- cell fractions, respectively, between type 1 diabetes-specific autoantibody-positive individuals and control participants. The analysis of pre-seroconversion samples identified DNA methylation signatures at the very early stage of disease, including differential methylation at the promoter of IRF5 in CD4(+) T cells. Further, we validated RRBS results using pyrosequencing at the following CpG sites: chr19:18118304 in the promoter of ARRDC2; chr21:47307815 in the intron of PCBP3; and chr14:81128398 in the intergenic region near TRAF3 in CD4(+) T cells. Conclusions/interpretation These preliminary results provide novel insights into cell type-specific differential epigenetic regulation of genes, which may contribute to type 1 diabetes pathogenesis at the very early stage of disease development. Should these findings be validated, they may serve as a potential signature useful for disease prediction and management.Peer reviewe

Population differences in the length and early-life dynamics of telomeres among European pied flycatchers

Telomere length and shortening rate are increasingly being used as biomarkers for long-term costs in ecological and evolutionary studies because of their relationships with survival and fitness. Both early-life conditions and growth, and later-life stressors can create variation in telomere shortening rate. Studies on between-population telomere length and dynamics are scarce, despite the expectation that populations exposed to varying environmental constraints would present divergent telomere length patterns. The pied flycatcher (Ficedula hypoleuca) is a passerine bird breeding across Eurasia (from Spain to western Siberia) and migrating through the Iberian Peninsula to spend the nonbreeding period in sub-Saharan Africa. Thus, different populations show marked differences in migration distance. We studied the large-scale variation of telomere length and early-life dynamics in the pied flycatcher by comparing six European populations across a north-south gradient (Finland, Estonia, England and Spain) predicting a negative effect of migration distance on adult telomere length, and of nestling growth on nestling telomere dynamics. There were clear population differences in telomere length, with English birds from midlatitudes having the longest telomeres. Telomere length did not thus show consistent latitudinal variation and was not linearly linked to differences in migration distance. Early-life telomere shortening rate tended to vary between populations. Fast growth was associated with shorter telomeres in the early life, but faster nestling growth affected telomeres more negatively in northern than southern populations. While the sources of between-population differences in telomere-related biology remain to be more intensively studied, our study illustrates the need to expand telomere studies at the between-population level

Early DNA methylation changes in children developing beta cell autoimmunity at a young age

Aims/hypothesis Type 1 diabetes is a chronic autoimmune disease of complex aetiology, including a potential role for epigenetic regulation. Previous epigenomic studies focused mainly on clinically diagnosed individuals. The aim of the study was to assess early DNA methylation changes associated with type 1 diabetes already before the diagnosis or even before the appearance of autoantibodies.Methods Reduced representation bisulphite sequencing (RRBS) was applied to study DNA methylation in purified CD4(+) T cell, CD8(+) T cell and CD4(-)CD8(-) cell fractions of 226 peripheral blood mononuclear cell samples longitudinally collected from seven type 1 diabetes-specific autoantibody-positive individuals and control individuals matched for age, sex, HLA risk and place of birth. We also explored correlations between DNA methylation and gene expression using RNA sequencing data from the same samples. Technical validation of RRBS results was performed using pyrosequencing.Results We identified 79, 56 and 45 differentially methylated regions in CD4(+) T cells, CD8(+) T cells and CD4-CD8- cell fractions, respectively, between type 1 diabetes-specific autoantibody-positive individuals and control participants. The analysis of pre-seroconversion samples identified DNA methylation signatures at the very early stage of disease, including differential methylation at the promoter of IRF5 in CD4(+) T cells. Further, we validated RRBS results using pyrosequencing at the following CpG sites: chr19:18118304 in the promoter of ARRDC2; chr21:47307815 in the intron of PCBP3; and chr14:81128398 in the intergenic region near TRAF3 in CD4(+) T cells.Conclusions/interpretation These preliminary results provide novel insights into cell type-specific differential epigenetic regulation of genes, which may contribute to type 1 diabetes pathogenesis at the very early stage of disease development. Should these findings be validated, they may serve as a potential signature useful for disease prediction and management.</p

Checkpoint kinase inhibitor AZD7762 strongly sensitises urothelial carcinoma cells to gemcitabine

Background: More effective chemotherapies are urgently needed for bladder cancer, a major cause of morbidity and mortality worldwide. We therefore explored the efficacy of the combination of gemcitabine and AZD7762, a checkpoint kinase 1/2 (CHK1/2) inhibitor, for bladder cancer. Methods: Viability, clonogenicity, cell cycle distribution and apoptosis were assessed in urothelial cancer cell lines and various non-malignant urothelial cells treated with gemcitabine and AZD7762. DNA damage was assessed by ?H2A.X and 53-BP1 staining and checkpoint activation was followed by Western blotting. Pharmacological inhibition of CHK1 and CHK2 was compared to downregulation of either CHK1 or CHK2 using siRNAs. Results: Combined use of gemcitabine and AZD7762 synergistically reduced urothelial carcinoma cell viability and colony formation relative to either single treatment. Non-malignant urothelial cells were substantially less sensitive to this drug combination. Gemcitabine plus AZD7762 inhibited cell cycle progression causing cell accumulation in S-phase. Moreover, the combination induced pronounced levels of apoptosis as indicated by an increase in the fraction of sub-G1 cells, in the levels of cleaved PARP, and in caspase 3/7 activity. Mechanistic investigations showed that AZD7762 treatment inhibited the repair of gemcitabine-induced double strand breaks by interference with CHK1, since siRNA-mediated depletion of CHK1 but not of CHK2 mimicked the effects of AZD7762. Conclusions: AZD7762 enhanced sensitivity of urothelial carcinoma cells to gemcitabine by inhibiting DNA repair and disturbing checkpoints. Combining gemcitabine with CHK1 inhibition holds promise for urothelial cancer therapy

Geographical trends in the yolk carotenoid composition of the pied flycatcher (Ficedula hypoleuca)

Carotenoids in the egg yolks of birds are considered to be important antioxidants and immune stimulants during the rapid growth of embryos. Yolk carotenoid composition is strongly affected by the carotenoid composition of the female’s diet at the time of egg formation. Spatial and temporal differences in carotenoid availability may thus be reflected in yolk concentrations. To assess whether yolk carotenoid concentrations or carotenoid profiles show any large-scale geographical trends or differences among habitats, we collected yolk samples from 16 European populations of the pied flycatcher, Ficedula hypoleuca. We found that the concentrations and proportions of lutein and some other xanthophylls in the egg yolks decreased from Central Europe northwards. The most southern population (which is also the one found at the highest altitude) also showed relatively low carotenoid levels. Concentrations of β-carotene and zeaxanthin did not show any obvious geographical gradients. Egg yolks also contained proportionally more lutein and other xanthophylls in deciduous than in mixed or coniferous habitats. We suggest that latitudinal gradients in lutein and xanthophylls reflect the lower availability of lutein-rich food items in the northern F. hypoleuca populations and in montane southern populations, which start egg-laying earlier relative to tree phenology than the Central European populations. Similarly, among-habitat variation is likely to reflect the better availability of lutein-rich food in deciduous forests. Our study is the first to indicate that the concentration and profile of yolk carotenoids may show large-scale spatial variation among populations in different parts of the species’ geographical range. Further studies are needed to test the fitness effects of this geographical variation

Acquired resistance to oxaliplatin is not directly associated with increased resistance to DNA damage in SK-N-ASrOXALI4000, a newly established oxaliplatin-resistant sub-line of the neuroblastoma cell line SK-N-AS

The formation of acquired drug resistance is a major reason for the failure of anti-cancer therapies after initial response. Here, we introduce a novel model of acquired oxaliplatin resistance, a sub-line of the non-MYCN-amplified neuroblastoma cell line SK-N-AS that was adapted to growth in the presence of 4000 ng/mL oxaliplatin (SK-N-ASrOXALI4000). SK-N-ASrOXALI4000 cells displayed enhanced chromosomal aberrations compared to SK-N-AS, as indicated by 24-chromosome fluorescence in situ hybridisation. Moreover, SK-N-ASrOXALI4000 cells were resistant not only to oxaliplatin but also to the two other commonly used anti-cancer platinum agents cisplatin and carboplatin. SK-N-ASrOXALI4000 cells exhibited a stable resistance phenotype that was not affected by culturing the cells for 10 weeks in the absence of oxaliplatin. Interestingly, SK-N-ASrOXALI4000 cells showed no cross resistance to gemcitabine and increased sensitivity to doxorubicin and UVC radiation, alternative treatments that like platinum drugs target DNA integrity. Notably, UVC-induced DNA damage is thought to be predominantly repaired by nucleotide excision repair and nucleotide excision repair has been described as the main oxaliplatin-induced DNA damage repair system. SK-N-ASrOXALI4000 cells were also more sensitive to lysis by influenza A virus, a candidate for oncolytic therapy, than SK-N-AS cells. In conclusion, we introduce a novel oxaliplatin resistance model. The oxaliplatin resistance mechanisms in SK-N-ASrOXALI4000 cells appear to be complex and not to directly depend on enhanced DNA repair capacity. Models of oxaliplatin resistance are of particular relevance since research on platinum drugs has so far predominantly focused on cisplatin and carboplatin