45 research outputs found

    The influence of formal education, years of service and team meetings on the quality of interaction in Austrian centre-based settings for children under 3 years

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    Previous studies have reviewed positive correlations between the formal education levels of educators in Early Childhood Education and Care (ECEC) centres and the quality of interactions, but the findings have not been consistent (Early et al., 2007; Manning et al., 2017). Moreover, informal learning processes seem to be important too (Pianta et al., 2016). The present paper addresses this and explores how education levels of ECEC staff, years of service, and the frequency of team meetings relate to the quality of interactions in Austrian centre-based settings for children under 3 years. The interaction quality was measured among early childhood educators and assistants (N = 116) using the Graz Scale of Interaction Quality for Children between 0 and 3 years (GrazIAS 0-3) (Walter-Laager, Flöter et al., 2019). The results of multiple regression models indicate that the frequency of team meetings strongly positively correlates with both the subscales of interaction quality, 'ensure relationships and wellbeing' and 'support learning'. Further, the level of education of the ECEC staff and their years of service positively correlate with the subscale 'support learning' with low-to-medium effect sizes. The findings also suggest that team meetings might be important for increasing the quality of interactions at ECEC centres.Previous studies have reviewed positive correlations between the formal education levels of educators in Early Childhood Education and Care (ECEC) centres and the quality of interactions, but the findings have not been consistent (Early et al., 2007; Manning et al., 2017). Moreover, informal learning processes seem to be important too (Pianta et al., 2016). The present paper addresses this and explores how education levels of ECEC staff, years of service, and the frequency of team meetings relate to the quality of interactions in Austrian centre-based settings for children under 3 years. The interaction quality was measured among early childhood educators and assistants (N = 116) using the Graz Scale of Interaction Quality for Children between 0 and 3 years (GrazIAS 0-3) (Walter-Laager, Flöter et al., 2019). The results of multiple regression models indicate that the frequency of team meetings strongly positively correlates with both the subscales of interaction quality, 'ensure relationships and wellbeing' and 'support learning'. Further, the level of education of the ECEC staff and their years of service positively correlate with the subscale 'support learning' with low-to-medium effect sizes. The findings also suggest that team meetings might be important for increasing the quality of interactions at ECEC centres

    Concurrent MEK targeted therapy prevents MAPK pathway reactivation during BRAFV600E targeted inhibition in a novel syngeneic murine glioma model.

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    Inhibitors of BRAFV600E kinase are currently under investigations in preclinical and clinical studies involving BRAFV600E glioma. Studies demonstrated clinical response to such individualized therapy in the majority of patients whereas in some patients tumors continue to grow despite treatment. To study resistance mechanisms, which include feedback activation of mitogen-activated protein kinase (MAPK) signaling in melanoma, we developed a luciferase-modified cell line (2341luc) from a BrafV600E mutant and Cdkn2a- deficient murine high-grade glioma, and analyzed its molecular responses to BRAFV600E- and MAPK kinase (MEK)-targeted inhibition. Immunocompetent, syngeneic FVB/N mice with intracranial grafts of 2341luc were tested for effects of BRAFV600E and MEK inhibitor treatments, with bioluminescence imaging up to 14-days after start of treatment and survival analysis as primary indicators of inhibitor activity. Intracranial injected tumor cells consistently generated high-grade glioma-like tumors in syngeneic mice. Intraperitoneal daily delivery of BRAFV600E inhibitor dabrafenib only transiently suppressed MAPK signaling, and rather increased Akt signaling and failed to extend survival for mice with intracranial 2341luc tumor. MEK inhibitor trametinib delivered by oral gavage daily suppressed MAPK pathway more effectively and had a more durable anti-growth effect than dabrafenib as well as a significant survival benefit. Compared with either agent alone, combined BRAFV600E and MEK inhibitor treatment was more effective in reducing tumor growth and extending animal subject survival, as corresponding to sustained MAPK pathway inhibition. Results derived from the 2341luc engraftment model application have clinical implications for the management of BRAFV600E glioma

    HIF1α Induces the Recruitment of Bone Marrow-Derived Vascular Modulatory Cells to Regulate Tumor Angiogenesis and Invasion

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    SummaryDevelopment of hypoxic regions is an indicator of poor prognosis in many tumors. Here, we demonstrate that HIF1α, the direct effector of hypoxia, partly through increases in SDF1α, induces recruitment of bone marrow-derived CD45+ myeloid cells containing Tie2+, VEGFR1+, CD11b+, and F4/80+ subpopulations, as well as endothelial and pericyte progenitor cells to promote neovascularization in glioblastoma. MMP-9 activity of bone marrow-derived CD45+ cells is essential and sufficient to initiate angiogenesis by increasing VEGF bioavailability. In the absence of HIF1α, SDF1α levels decrease, and fewer BM-derived cells are recruited to the tumors, decreasing MMP-9 and mobilization of VEGF. VEGF also directly regulates tumor cell invasiveness. When VEGF activity is impaired, tumor cells invade deep into the brain in the perivascular compartment

    miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells

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    Glioblastoma multiforme (GBM) is an invariably fatal central nervous system tumor despite treatment with surgery, radiation, and chemotherapy. Further insights into the molecular and cellular mechanisms that drive GBM formation are required to improve patient outcome. MicroRNAs are emerging as important regulators of cellular differentiation and proliferation, and have been implicated in the etiology of a variety of cancers, yet the role of microRNAs in GBM remains poorly understood. In this study, we investigated the role of microRNAs in regulating the differentiation and proliferation of neural stem cells and glioblastoma-multiforme tumor cells.status: publishe

    Asymmetric cell division of stem and progenitor cells during homeostasis and cancer.

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    Stem and progenitor cells are characterized by their ability to self-renew and produce differentiated progeny. A fine balance between these processes is achieved through controlled asymmetric divisions and is necessary to generate cellular diversity during development and to maintain adult tissue homeostasis. Disruption of this balance may result in premature depletion of the stem/progenitor cell pool, or abnormal growth. In many tissues, including the brain, dysregulated asymmetric divisions are associated with cancer. Whether there is a causal relationship between asymmetric cell division defects and cancer initiation is as yet not known. Here, we review the cellular and molecular mechanisms that regulate asymmetric cell divisions in the neural lineage and discuss the potential connections between this regulatory machinery and cancer
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