Fair Price and Fair Play under the Montana Business Corporation Act

Fair Price and Fair Play under the Montana Business Corporation Ac

p75(NTR)-dependent activation of NF-κB regulates microRNA-503 transcription and pericyte-endothelial crosstalk in diabetes after limb ischaemia

The communication between vascular endothelial cells (ECs) and pericytes in the microvasculature is fundamental for vascular growth and homeostasis; however, these processes are disrupted by diabetes. Here we show that modulation of p75NTR expression in ECs exposed to high glucose activates transcription of miR-503, which negatively affects pericyte function. p75NTR activates NF-κB to bind the miR-503 promoter and upregulate miR-503 expression in ECs. NF-κB further induces activation of Rho kinase and shedding of endothelial microparticles carrying miR-503, which transfer miR-503 from ECs to vascular pericytes. The integrin-mediated uptake of miR-503 in the recipient pericytes reduces expression of EFNB2 and VEGFA, resulting in impaired migration and proliferation. We confirm operation of the above mechanisms in mouse models of diabetes, in which EC-derived miR-503 reduces pericyte coverage of capillaries, increased permeability and impaired post-ischaemic angiogenesis in limb muscles. Collectively, our data demonstrate that miR-503 regulates pericyte–endothelial crosstalk in microvascular diabetic complications

School well-being of students with and without special educational needs - a comparison of students in inclusive and regular classes

Schwab S, Rossmann P, Tanzer N, et al. Schulisches Wohlbefinden von SchülerInnen mit und ohne sonderpädagogischem Förderbedarf - Integrations- und Regelklassen im Vergleich. Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie. 2015;43(4):265-274.Objective: The present study examines the academic well-being of students with and without special educational needs (SEN) in inclusive classes compared to students from regular classes in which no child with SEN is taught. In addition, the relationships between the school well-being and emotional problems, conduct problems, hyperactivity/inattention, peer relationship problems and prosocial behavior are analyzed. Method: A total of 1115 students from the 4th and 7th grade (37 % 4th graders, 63 % 7th graders) participated in the survey, 126 of whom had been diagnosed as having SEN. The subscale Well-Being at School taken from the FEESS 3-4 (Rauer & Schuck, 2004) and the SDQ (Goodman, 1997) were used for measurement. Results: Results indicate high reliabilities for the subscale Well-Being in School for students both with and without SEN for both grades 4 and 7. Furthermore, it could be shown that the variance explained for school well-being can be connected to elements on the students' individual level as well as on the class-specific level. Significant predictors of school well-being were sex, behavioral difficulties and strengths as well as the school grade. The SEN status (no SEN vs. SEN) and the class setting (regular vs. inclusive class) did not influence the school well-being significantly

Enhancement of lipopolysaccharide-stimulated JNK activity in rat aortic smooth muscle cells by pharmacological and adenovirus-mediated inhibition of inhibitory kappa B kinase signalling

1. In rat aortic smooth muscle cells (RASMCs), the putative nuclear factor kappa B (NFκB) inhibitor Pyrrolidine dithiocarbamate (PDTC) was found to inhibit lipopolysaccharide (LPS)-stimulated NFκB DNA-binding. However, further investigation identified the site of inhibition as being at, or upstream of, the inhibitory kappa B kinases (IKKs) as their kinase activity was substantially reduced. 2. In addition, PDTC potentiated LPS-stimulated c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAP kinase) and MAP kinase-activated protein kinase-2 activity (the downstream target of p38 MAP kinase). 3. Another inhibitor of NFκB signalling, the serine protease inhibitor Nαp-tosyl-L-lysine chloro-methylketone (TLCK), also inhibited LPS-stimulated IKK activity and potentiated JNK activity in response to LPS, suggesting that cross-talk may occur between the NFκB and stress-activated protein kinase pathways at the level of IKK or at a common point upstream. 4. Infection of RASMCs with an adenovirus encoding either inhibitory kappa Bα or a dominant-negative IKKβ potentiated LPS-stimulated JNK activity. 5. These studies therefore suggest that the loss of NFκB DNA-binding and resultant transcriptional activity, rather than the loss of IKK activity, is sufficient to cause an increase in JNK activity. This shows that either pharmacological or molecular inhibition of NFκB DNA-binding enhances JNK activation in vascular smooth muscle cells, an effect that may contribute to the pathophysiological effects of LPS