16 research outputs found
Loss of Ezh2 promotes a midbrain-to-forebrain identity switch by direct gene derepression and Wnt-dependent regulation
Experimentelle Untersuchung des Einflusses von Ă„sthetik auf Leistung - Die Bedeutung von Affekt und des BedĂĽrfnisses nach Ă„sthetik
Paruzel A, Klug HJP, NĂĽbold A. Experimentelle Untersuchung des Einflusses von Ă„sthetik auf Leistung - Die Bedeutung von Affekt und des BedĂĽrfnisses nach Ă„sthetik. Presented at the 48. Kongress der DGPs, Bochum
Assessment of upper extremity movement performance of patients with obstetric brachial plexus palsy
Coping strategies of patients with obstetric brachial plexus palsy (OBPP) are highly individual. Up to now, individual movement performance is assessed by visual observations of physicians or therapists - a procedure, which is highly subjective and lacks objective data. However, objective data about the individual movement performance are the key to evidence-based and individualized treatment. In this paper, a new approach is presented, which provides objective information about the upper extremity movement performance of patients with OBPP. The approach is based on the use of accelerometers in combination with a classification procedure. The movement performance of 10 healthy volunteers and 41 patients with OBPP has been evaluated by experienced physiotherapists and has been assigned to one of 4 categories representing the Mallet Scale (MS) IV to I. Three triaxial-accelerometers were placed at chest, upper arm and wrist of the affected side of the patient. Acceleration signals have been recorded during repetitive movements with relevance regarding daily life. Here, especially the results from the “hand to mouth” task are presented. From the 9 recorded acceleration signals 13 relevant features were extracted. For each of the 13 features 4 thresholds have been determined distinguishing best between the 4 patient categories of the MS and the healthy subjects. With respect to the thresholds each feature value has been assigned to the discrete numbers 0, 1, 2, 3 or 4. Afterwards, each discrete number has been weighted by a factor regarding the correlation between the feature’s value and the MS score. The resulting weighted discrete numbers of all 13 features have been added resulting in a score, which quantifies the individual upper extremity movement performance. Based on this score the movement performance of each patient has been assigned to the classes “very good”, “good”, “regular” and “bad”. All movements of the 10 healthy volunteers were classified as “very good”. The movement performance of two patients MS IV were classified as “very good” as well and the movements of the other 16 patients as “good”. The movements of the entire group of MS III patients fell into the class “regular”. Just one MS II patient was assigned to the class “regular” while the others were classified as “bad”. It was not possible to classify the movements of MS I patients. This was mainly due to the fact that none of these patients MS I was able to complete the task successfully. The developed approach demonstrated its ability to quantify the movement performance of upper extremity movements based on accelerometers. This provides an easy to use tool to assess patient’s movement strategies during daily tasks for diagnosis and rehabilitation
Phosphodiesterase-4 Inhibition Reduces Cutaneous Inflammation and IL-1β Expression in a Psoriasiform Mouse Model but Does Not Inhibit Inflammasome Activation
Apremilast (Otezla®) is an oral small molecule phosphodiesterase 4 (PDE4) inhibitor approved for the treatment of psoriasis, psoriatic arthritis, and oral ulcers associated with Behçet’s disease. While PDE4 inhibition overall is mechanistically understood, the effect of apremilast on the innate immune response, particularly inflammasome activation, remains unknown. Here, we assessed the effect of apremilast in a psoriasis mouse model and primary human cells. Psoriatic lesion development in vivo was studied in K5.Stat3C transgenic mice treated with apremilast for 2 weeks, resulting in a moderate (2 mg/kg/day) to significant (6 mg/kg/day) resolution of inflamed plaques after 2-week treatment. Concomitantly, epidermal thickness dramatically decreased, the cutaneous immune cell infiltrate was reduced, and proinflammatory cytokines were significantly downregulated. Additionally, apremilast significantly inhibited lipopolysaccharide- or anti-CD3-induced expression of proinflammatory cytokines in peripheral mononuclear cells (PBMCs). Notably, inflammasome activation and secretion of IL-1β were not inhibited by apremilast in PBMCs and in human primary keratinocytes. Collectively, apremilast effectively alleviated the psoriatic phenotype of K5.Stat3 transgenic mice, further substantiating PDE4 inhibitor-efficiency in targeting key clinical, histopathological and inflammatory features of psoriasis. Despite lacking direct effect on inflammasome activation, reduced priming of inflammasome components upon apremilast treatment reflected the indirect benefit of PDE4 inhibition in reducing inflammation
Yin Yang 1 sustains biosynthetic demands during brain development in a stage-specific manner
The transcription factor Yin Yang 1 (YY1) plays an important role in human disease. It is often overexpressed in cancers and mutations can lead to a congenital haploinsufficiency syndrome characterized by craniofacial dysmorphisms and neurological dysfunctions, consistent with a role in brain development. Here, we show that Yy1 controls murine cerebral cortex development in a stage-dependent manner. By regulating a wide range of metabolic pathways and protein translation, Yy1 maintains proliferation and survival of neural progenitor cells (NPCs) at early stages of brain development. Despite its constitutive expression, however, the dependence on Yy1 declines over the course of corticogenesis. This is associated with decreasing importance of processes controlled by Yy1 during development, as reflected by diminished protein synthesis rates at later developmental stages. Thus, our study unravels a novel role for Yy1 as a stage-dependent regulator of brain development and shows that biosynthetic demands of NPCs dynamically change throughout development.status: publishe
Yin Yang 1 sustains biosynthetic demands during brain development in a stage-specific manner
The transcription factor Yin Yang 1 (YY1) plays an important role in human disease. It is often overexpressed in cancers and mutations can lead to a congenital haploinsufficiency syndrome characterized by craniofacial dysmorphisms and neurological dysfunctions, consistent with a role in brain development. Here, we show that Yy1 controls murine cerebral cortex development in a stage-dependent manner. By regulating a wide range of metabolic pathways and protein translation, Yy1 maintains proliferation and survival of neural progenitor cells (NPCs) at early stages of brain development. Despite its constitutive expression, however, the dependence on Yy1 declines over the course of corticogenesis. This is associated with decreasing importance of processes controlled by Yy1 during development, as reflected by diminished protein synthesis rates at later developmental stages. Thus, our study unravels a novel role for Yy1 as a stage-dependent regulator of brain development and shows that biosynthetic demands of NPCs dynamically change throughout development
Loss of Ezh2 promotes a midbrain-to-forebrain identity switch by direct gene derepression and Wnt-dependent regulation
BACKGROUND: Precise spatiotemporal control of gene expression is essential for the establishment of correct cell numbers and identities during brain development. This process involves epigenetic control mechanisms, such as those mediated by the polycomb group protein Ezh2, which catalyzes trimethylation of histone H3K27 (H3K27me3) and thereby represses gene expression.
RESULTS: Herein, we show that Ezh2 plays a crucial role in the development and maintenance of the midbrain. Conditional deletion of Ezh2 in the developing midbrain resulted in decreased neural progenitor proliferation, which is associated with derepression of cell cycle inhibitors and negative regulation of Wnt/β-catenin signaling. Of note, Ezh2 ablation also promoted ectopic expression of a forebrain transcriptional program involving derepression of the forebrain determinants Foxg1 and Pax6. This was accompanied by reduced expression of midbrain markers, including Pax3 and Pax7, as a consequence of decreased Wnt/β-catenin signaling.
CONCLUSION: Ezh2 is required for appropriate brain growth and maintenance of regional identity by H3K27me3-mediated gene repression and control of canonical Wnt signaling
Teachers’ assessment competence: Integrating knowledge-, process-, and product-oriented approaches into a competence-oriented conceptual model
In this article, we present a new model of teachers' assessment competence. The model is based on the educational competence concept, thus defining competences to be context-specific, learnable cognitive dispositions that are needed to successfully cope with specific situations. Integrating research on assessment processes, practices, and products, we specify the range of situations our model applies to, and discuss how its elements may become involved and measurable in a variable assessment process. The model aims to inspire future integrative research on the description, explanation, prediction, and promotion of teachers' assessments in various situations
Ein Arbeitsmodell für die empirische Erforschung der diagnostischen Kompetenz von Lehrkräften
Additional file 1: Figure S1. of Loss of Ezh2 promotes a midbrain-to-forebrain identity switch by direct gene derepression and Wnt-dependent regulation
(Related to Fig. 1) Ezh2 expression is lost from E10.5. Figure S2. (related to Fig. 2) Ezh2 ablation results in increased neurogenesis. Figure S3. (related to Fig. 3) Gene ontology analysis. Figure S4. (related to Fig. 4) Expression levels of forebrain transcription factors in Ezh2 cko midbrain do not reach those of wildtype forebrain. Figure S5. (related to Fig. 4) Incomplete Cre-mediated recombination in the dorsal midbrain. Figure S6. (related to Fig. 5) Ezh2 ablation does not affect early midbrain patterning. Figure S7. (related to Fig. 6) Pax6 does not directly repress Pax3 and Pax7. Table S1. (related to Fig. 3) Differentially expressed genes of E10.5 control and Ezh2 cko midbrains. Table S2. Primers used for the generation of in situ probes by in vitro transcription. Table S3. Primers used for quantitative real-time PCR on embryo tissue samples. Table S4. Primers used for quantitative real-time PCR on DNA fragments isolated in H3K27me3 ChIP assay. (PDF 4989 kb