How to study basement membrane stiffness as a biophysical trigger in prostate cancer and other age-related pathologies or metabolic diseases

Here we describe a protocol that can be used to study the biophysical microenvironment related to increased thickness and stiffness of the basement membrane (BM) during age-related pathologies and metabolic disorders (e.g. cancer, diabetes, microvascular disease, retinopathy, nephropathy and neuropathy). The premise of the model is non-enzymatic crosslinking of reconstituted BM (rBM) matrix by treatment with glycolaldehyde (GLA) to promote advanced glycation endproduct (AGE) generation via the Maillard reaction. Examples of laboratory techniques that can be used to confirm AGE generation, non-enzymatic crosslinking and increased stiffness in GLA treated rBM are outlined. These include preparation of native rBM (treated with phosphate-buffered saline, PBS) and stiff rBM (treated with GLA) for determination of: its AGE content by photometric analysis and immunofluorescent microscopy, its non-enzymatic crosslinking by ((sodium dodecyl sulfate polyacrylamide gel electrophoresis)) (SDS PAGE) as well as confocal microscopy, and its increased stiffness using rheometry. The procedure described here can be used to increase the rigidity (elastic moduli, E) of rBM up to 3.2-fold, consistent with measurements made in healthy versus diseased human prostate tissue. To recreate the biophysical microenvironment associated with the aging and diseased prostate gland three prostate cell types were introduced on to native rBM and stiff rBM: RWPE-1, prostate epithelial cells (PECs) derived from a normal prostate gland; BPH-1, PECs derived from a prostate gland affected by benign prostatic hyperplasia (BPH); and PC3, metastatic cells derived from a secondary bone tumor originating from prostate cancer. Multiple parameters can be measured, including the size, shape and invasive characteristics of the 3D glandular acini formed by RWPE-1 and BPH-1 on native versus stiff rBM, and average cell length, migratory velocity and persistence of cell movement of 3D spheroids formed by PC3 cells under the same conditions. Cell signaling pathways and the subcellular localization of proteins can also be assessed

Der kompetenzorientierte Unterricht in Mathematik in der österreichischen Volksschule aus Sicht der Schüler/innen: Impulse für eine reflexive Unterrichtsentwicklung und -forschung

Ziel von Schule und Unterricht ist die Förderung der Kompetenzentwicklung bei Kindern und Jugendlichen, wobei die grundgelegte Definition von Kompetenz sowohl kognitive Komponenten als auch volitionale, motivationale und soziale umfasst. Der vorliegende Beitrag widmet sich dem Unterricht als Kern des schulischen Geschehens und analysiert wesentliche Dimensionen kompetenzorientierten Unterrichts. Dabei werfen wir einen empirischen Blick auf die Dimensionen Aktivierung, Wissensvernetzung, lebensweltliche Anwendung, personalisierte sowie gruppenorientierte Lernbegleitung, Reflexion, Klassenmanagement und Klassenführung, in dem die aggregierten Wahrnehmungen von Volksschulkindern (Grundschulkindern) für eine Beschreibung des Mathematikunterrichts in Österreich in der Grundschule herangezogen werden. (DIPF/Orig.

AGE-modified basement membrane cooperates with Endo180 to promote epithelial cell invasiveness and decrease prostate cancer survival

Biomechanical strain imposed by age-related thickening of the basal lamina and augmented tissue stiffness in the prostate gland coincides with increased cancer risk. Here we hypothesized that the structural alterations in the basal lamina associated with age can induce mechanotransduction pathways in prostate epithelial cells (PECs) to promote invasiveness and cancer progression. To demonstrate this, we developed a 3D model of PEC acini in which thickening and stiffening of basal lamina matrix was induced by advanced glycation end-product (AGE)-dependent non-enzymatic crosslinking of its major components, collagen IV and laminin. We used this model to demonstrate that antibody targeted blockade of CTLD2, the second of eight C-type lectin-like domains in Endo180 (CD280, CLEC13E, KIAA0709, MRC2, TEM9, uPARAP) that can recognize glycosylated collagens, reversed actinomyosin-based contractility [myosin-light chain-2 (MLC2) phosphorylation], loss of cell polarity, loss of cell–cell junctions, luminal infiltration and basal invasion induced by AGE-modified basal lamina matrix in PEC acini. Our in vitro results were concordant with luminal occlusion of acini in the prostate glands of adult Endo180ΔEx2–6/ΔEx2–6 mice, with constitutively exposed CTLD2 and decreased survival of men with early (non-invasive) prostate cancer with high epithelial Endo180 expression and levels of AGE. These findings indicate that AGE-dependent modification of the basal lamina induces invasive behaviour in non-transformed PECs via a molecular mechanism linked to cancer progression. This study provides a rationale for targeting CTLD2 in Endo180 in prostate cancer and other pathologies in which increased basal lamina thickness and tissue stiffness are driving factors

Vorwort zu: Praxistransfer Schul- und Unterrichtsentwicklung

Schreiner C, Wiesner C, Breit S, Dobbelstein P, Heinrich M, Steffens U. Vorwort zu: Praxistransfer Schul- und Unterrichtsentwicklung. In: Schreiner C, Wiesner C, Breit S, Dobbelstein P, Heinrich M, Steffens U, eds. Praxistransfer Schul- und Unterrichtsentwicklung. Münster: Waxmann; 2019: 7

Praxistransfer Schul- und Unterrichtsentwicklung

Der Wissenstransfer zwischen Bildungsforschung und Praxis stellt große Herausforderungen an die beteiligten Akteurinnen und Akteure. Es gilt dabei Wege zu finden, die unterschiedlichen Handlungslogiken und Erfordernisse, aber auch z.B. sprachliche Barrieren zwischen diesen Feldern zu überwinden und einen echten Dialog zu initiieren. Das Netzwerk „Empiriegestützte Schulentwicklung“ (EMSE) befasste sich auf seiner Tagung im Juni 2016 in Salzburg aus unterschiedlichen Perspektiven mit dem Themenkomplex „Transfer – Praxis/Wissenschaft – Wissenschaft/Praxis“. Ausgehend von dieser 22. EMSE-Tagung spannen die Beiträge in diesem Band ein breites Spektrum der Annäherung an diesen Themenkomplex von konzeptionellen Beiträgen bis zu Erfahrungsberichten auf und spiegeln so die Vielfalt der Zugänge im EMSE-Netzwerk wider

Praxistransfer Schul- und Unterrichtsentwicklung

Schreiner C, Wiesner C, Breit S, Dobbelstein P, Heinrich M, Steffens U, eds. Praxistransfer Schul- und Unterrichtsentwicklung. Münster: Waxmann; 2019

Evidenzbasierte Steuerung ohne „Evidenztransfer“? Zum Problem der mangelnden Professionssensibilität des Programms der Evidenzbasierung sowie den Chancen und Grenzen von Praxisforschung als Alternative oder Ergänzung

Heinrich M, Klewin G. Evidenzbasierte Steuerung ohne „Evidenztransfer“? Zum Problem der mangelnden Professionssensibilität des Programms der Evidenzbasierung sowie den Chancen und Grenzen von Praxisforschung als Alternative oder Ergänzung. In: Schreiner C, Wiesner C, Breit S, Dobbelstein P, Heinrich M, Steffens U, eds. Praxistransfer Schul- und Unterrichtsentwicklung. Münster: Waxmann; 2019: 61-77

Praxistransfer Schul- und Unterrichtsforschung – eine Problemskizze

Steffens U, Heinrich M, Dobbelstein P. Praxistransfer Schul- und Unterrichtsforschung – eine Problemskizze. In: Schreiner C, Wiesner C, Breit S, Dobbelstein P, Heinrich M, Steffens U, eds. Praxistransfer Schul- und Unterrichtsentwicklung. Münster: Waxmann; 2019: 11-26

Reduced corticolimbic habituation to negative stimuli characterizes bipolar depressed suicide attempters.

Suicide attempts in Bipolar Disorder are characterized by high levels of lethality and impulsivity. Reduced rates of amygdala and cortico-limbic habituation can identify a fMRI phenotype of suicidality in the disorder related to internal over-arousing states. Hence, we investigated if reduced amygdala and whole-brain habituation may differentiate bipolar suicide attempters (SA, n = 17) from non-suicide attempters (nSA, n = 57), and healthy controls (HC, n = 32). Habituation was assessed during a fMRI task including facial expressions of anger and fear and a control condition. Associations with suicidality and current depressive symptomatology were assessed, including machine learning procedure to estimate the potentiality of habituation as biomarker for suicidality. SA showed lower habituation compared to HC and nSA in several cortico-limbic areas, including amygdalae, cingulate and parietal cortex, insula, hippocampus, para-hippocampus, cerebellar vermis, thalamus, and striatum, while nSA displayed intermediate rates between SA and HC. Lower habituation rates in the amygdalae were also associated with higher depressive and suicidal current symptomatology. Machine learning on whole-brain and amygdala habituation differentiated SA vs. nSA with 94% and 69% of accuracy, respectively. Reduced habituation in cortico-limbic system can identify a candidate biomarker for attempting suicide, helping in detecting at-risk bipolar patients, and in developing new therapeutic interventions

Über Praxisforschung zum Transfer von Innovationen?

Hahn S, Klewin G, Koch B, Kuhnen SU, Palowski M, Stiller C. Über Praxisforschung zum Transfer von Innovationen? In: Schreiner C, Wiesner C, Breit S, Dobbelstein P, Heinrich M, Steffens U, eds. Praxistransfer Schul- und Unterrichtsforschung. Münster: Waxmann ; 2019: 141-152