Mehr Praxis im künstlerischen Lehramtsstudium! Welche Praxis? Bildungswissenschaftliche Beiträge zur Schulpraxis

Im Beitrag gehen die Autorinnen auf Besonderheiten des künstlerischen Lehramtsstudiums ein und betonen vor dem Hintergrund der fachlichen und institutionellen Spezifika die curriculare Verankerung von praxisbezogenen Lehrveranstaltungen sowie Formen der Begleitung und Kooperation. Im Fokus steht die Frage, welchen Beitrag der Anteil der allgemeinen bildungswissenschaftlichen Grundlagen zur Schulpraxis leistet. (DIPF/Orig.

Environmental enrichment induces behavioural disturbances in neuropeptide Y knockout mice

Environmental enrichment (EE) refers to the provision of a complex and stimulating housing condition which improves well-being, behaviour and brain function of laboratory animals. The mechanisms behind these beneficial effects of EE are only partially understood. In the current report, we describe a link between EE and neuropeptide Y (NPY), based on findings from NPY knockout (KO) mice exposed to EE. Relative to EE-housed wildtype (WT) animals, NPY KO mice displayed altered behaviour as well as molecular and morphological changes in amygdala and hippocampus. Exposure of WT mice to EE reduced anxiety and decreased central glucocorticoid receptor expression, effects which were absent in NPY KO mice. In addition, NPY deletion altered the preference of EE items, and EE-housed NPY KO mice responded to stress with exaggerated hyperthermia, displayed impaired spatial memory, had higher hippocampal brain-derived neurotrophic factor mRNA levels and altered hippocampal synaptic plasticity, effects which were not seen in WT mice. Accordingly, these findings suggest that NPY contributes to the anxiolytic effect of EE and that NPY deletion reverses the beneficial effects of EE into a negative experience. The NPY system could thus be a target for "enviromimetics", therapeutics which reproduce the beneficial effects of enhanced environmental stimulation.status: publishe

Spatial tumour gene signature discriminates neoplastic from non-neoplastic compartments in colon cancer: unravelling predictive biomarkers for relapse

Abstract Background Opting for or against the administration of adjuvant chemotherapy in therapeutic management of stage II colon cancer remains challenging. Several studies report few survival benefits for patients treated with adjuvant therapy and additionally revealing potential side effects of overtreatment, including unnecessary exposure to chemotherapy-induced toxicities and reduced quality of life. Predictive biomarkers are urgently needed. We, therefore, hypothesise that the spatial tissue composition of relapsed and non-relapsed colon cancer stage II patients reveals relevant biomarkers. Methods The spatial tissue composition of stage II colon cancer patients was examined by a novel spatial transcriptomics technology with sub-cellular resolution, namely in situ sequencing. A panel of 176 genes investigating specific cancer-associated processes such as apoptosis, proliferation, angiogenesis, stemness, oxidative stress, hypoxia, invasion and components of the tumour microenvironment was designed to examine differentially expressed genes in tissue of relapsed versus non-relapsed patients. Therefore, FFPE slides of 10 colon cancer stage II patients either classified as relapsed (5 patients) or non-relapsed (5 patients) were in situ sequenced and computationally analysed. Results We identified a tumour gene signature that enables the subclassification of tissue into neoplastic and non-neoplastic compartments based on spatial expression patterns obtained through in situ sequencing. We developed a computational tool called Genes-To-Count (GTC), which automates the quantification of in situ signals, accurately mapping their position onto the spatial tissue map and automatically identifies neoplastic and non-neoplastic tissue compartments. The GTC tool was used to quantify gene expression of biological processes upregulated within the neoplastic tissue in comparison to non-neoplastic tissue and within relapsed versus non-relapsed stage II colon patients. Three differentially expressed genes (FGFR2, MMP11 and OTOP2) in the neoplastic tissue compartments of relapsed patients in comparison to non-relapsed patients were identified predicting recurrence in stage II colon cancer. Conclusions In depth spatial in situ sequencing showed potential to provide a deeper understanding of the underlying mechanisms involved in the recurrence of disease and revealed novel potential predictive biomarkers for disease relapse in colon cancer stage II patients. Our open-access GTC-tool allowed us to accurately capture the tumour compartment and quantify spatial gene expression in colon cancer tissue

Early remodeling of perinuclear Ca2+ stores and nucleoplasmic Ca2+ signaling during the development of hypertrophy and heart failure.

BackgroundA hallmark of heart failure is impaired cytoplasmic Ca(2+) handling of cardiomyocytes. It remains unknown whether specific alterations in nuclear Ca(2+) handling via altered excitation-transcription coupling contribute to the development and progression of heart failure.Methods and resultsUsing tissue and isolated cardiomyocytes from nonfailing and failing human hearts, as well as mouse and rabbit models of hypertrophy and heart failure, we provide compelling evidence for structural and functional changes of the nuclear envelope and nuclear Ca(2+) handling in cardiomyocytes as remodeling progresses. Increased nuclear size and less frequent intrusions of the nuclear envelope into the nuclear lumen indicated altered nuclear structure that could have functional consequences. In the (peri)nuclear compartment, there was also reduced expression of Ca(2+) pumps and ryanodine receptors, increased expression of inositol-1,4,5-trisphosphate receptors, and differential orientation among these Ca(2+) transporters. These changes were associated with altered nucleoplasmic Ca(2+) handling in cardiomyocytes from hypertrophied and failing hearts, reflected as increased diastolic Ca(2+) levels with diminished and prolonged nuclear Ca(2+) transients and slowed intranuclear Ca(2+) diffusion. Altered nucleoplasmic Ca(2+) levels were translated to higher activation of nuclear Ca(2+)/calmodulin-dependent protein kinase II and nuclear export of histone deacetylases. Importantly, the nuclear Ca(2+) alterations occurred early during hypertrophy and preceded the cytoplasmic Ca(2+) changes that are typical of heart failure.ConclusionsDuring cardiac remodeling, early changes of cardiomyocyte nuclei cause altered nuclear Ca(2+) signaling implicated in hypertrophic gene program activation. Normalization of nuclear Ca(2+) regulation may therefore be a novel therapeutic approach to prevent adverse cardiac remodeling

Early Remodeling of Perinuclear Ca2+ Stores and Nucleoplasmic Ca2+ Signaling During the Development of Hypertrophy and Heart Failure

Background—A hallmark of heart failure is impaired cytoplasmic Ca2+ handling of cardiomyocytes. It remains unknown whether specific alterations in nuclear Ca2+ handling via altered excitation-transcription coupling contribute to the development and progression of heart failure. Methods and Results—Using tissue and isolated cardiomyocytes from nonfailing and failing human hearts, as well as mouse and rabbit models of hypertrophy and heart failure, we provide compelling evidence for structural and functional changes of the nuclear envelope and nuclear Ca2+ handling in cardiomyocytes as remodeling progresses. Increased nuclear size and less frequent intrusions of the nuclear envelope into the nuclear lumen indicated altered nuclear structure that could have functional consequences. In the (peri)nuclear compartment, there was also reduced expression of Ca2+ pumps and ryanodine receptors, increased expression of inositol-1,4,5-trisphosphate receptors, and differential orientation among these Ca2+ transporters. These changes were associated with altered nucleoplasmic Ca2+ handling in cardiomyocytes from hypertrophied and failing hearts, reflected as increased diastolic Ca2+ levels with diminished and prolonged nuclear Ca2+ transients and slowed intranuclear Ca2+ diffusion. Altered nucleoplasmic Ca2+ levels were translated to higher activation of nuclear Ca2+/calmodulin-dependent protein kinase II and nuclear export of histone deacetylases. Importantly, the nuclear Ca2+ alterations occurred early during hypertrophy and preceded the cytoplasmic Ca2+ changes that are typical of heart failure. Conclusions-During cardiac remodeling, early changes of cardiomyocyte nuclei cause altered nuclear Ca2+ signaling implicated in hypertrophic gene program activation. Normalization of nuclear Ca2+ regulation may therefore be a novel therapeutic approach to prevent adverse cardiac remodeling

Conventional electron microscopy of vacuoles in chordoma cells (arrows indicate the reduced connection of the vacuoles; mitochondria (M); nucleolus (N); vacuoles (V)).

<p>A) MUG-Chor1 cells show a prominent nucleus, abundant vacuoles with a diverse density of material. B) Higher magnification of large densely filled vacuoles. C) Overview of single vacuoles with barely visible contact zones between the vacuoles.</p

Structural association of mitochondrial membrane with the ER called MAM, represented by HPF.

<p>A) Abundant mitochondria within the cell, small connected vacuoles, and the connection of two chordoma cells with contact zones as well as excrescences (asterisk). B) Very close continuous contact zones of mitochondria (M) and ER. C) Connection of two chordoma cells with contact zones, excrescences (asterisk) and MAM complex.</p

Intracellular calcium response to four different agonists in MUG-Chor1 cells was measured.

<p>A) Histamine (His), acetylcholine (ACh), serotonin (5HT), and P2Y purinoceptor agonist mes-ATP were applied at a concentration of 10 µM for a period of 60 seconds as indicated by the grey bars; the ratio between 340 nm and 380 nm is given. After stimulation, the respective agonist was washed out for another 60 seconds. B) The first two peaks of ratio values of MUG-Chor1 cells indicate ACh-application in the presence of extracellular calcium (NT+[Ca²⁺]_ex; upper, open bar); peak reduction was induced by removing external calcium (NT w/o [Ca²⁺]_ex; upper, grey bar). Small bars represent the time of perfusion with ACh at the two different concentrations (10 µM: lower, grey bar; 100 µM: lower, black bar). C) Within the bar chart a summary of ACh-induced changes is given. The first two bars represent effects in [Ca²⁺]_i induced by ACh (10 µM; 100 µM) given as average value (± standard deviation) of the change in intracellular calcium concentration [Ca²⁺]_i (nM). The usage of calcium within the perfusion solution as well as the different concentrations of ACh is indicated below the x-axis. Significant changes evaluated by the students t-test are given (***, p<0.001; **, p<0.01).</p

HPF fixed vacuoles within the chordoma cells.

<p>All micrographs indicate the connection of the vacuoles. A) Overview of the vacuoles (V); arrows indicate the network within the MUG-Chor1 cells. B) Cells show a high number of small vacuoles connected to each other as well as endosomes and Golgi apparatus, surrounded by dense cytoplasm. C) Higher magnification enables the visualization of the linkages between either small vacuoles or endosomes and vacuoles; arrows indicate the exchange of material within the vacuoles.</p