Nitric oxide enhances de novo formation of endothelial gap junctions

Objective: Gap junctions (formed by connexins, Cx) are important for functional coordination of cells in the vascular wall. However, little is known about their physiological regulation in this tissue. We examined the effects of nitric oxide (NO), an important mediator of vasomotion, wound healing and angiogenesis, on the formation of gap junctions in endothelial cells (human umbilical vein endothelial cells, HUVEC). Methods: Flow cytometry was used to determine dye transfer through newly formed gap junctions between acutely coincubated HUVECs. Parallel experiments in wild-type HeLa cells (no connexins) and transfected HeLa cells exclusively expressing Cx43, Cx40 or Cx37 were performed to determine the specific role of Cx subtypes. The intracellular distribution of Cx40 was examined after fractionation with triton by Western blotting. Intracellular levels of cGMP and cAMP were measured by radioimmunoassay. Results: The NO donor SNAP (1 μM) enhanced gap-junctional coupling in HUVECs by about 40%. This was associated with an enhanced incorporation of Cx40 into the membrane. Both effects were restricted to Cx40 as analyzed in experiments with Cx-selective HeLa cells. The NO-induced increase in cell coupling was elicited by a corresponding rise of cGMP, which secondarily increased intracellular cAMP levels. The latter was an integral part of the signal cascade, since the protein kinase A (PKA) inhibitor H89 blocked the SNAP-induced incorporation of Cx40 into the plasma membrane. Conclusions: We conclude that NO is a potent modulator of gap-junctional coupling in endothelial cells. It enhances de novo formation of endothelial gap junctions by increasing incorporation of Cx40 into the plasma membrane due to PKA activation

Gap-junctional coupling between neutrophils and endothelial cells

Communication between leukocytes and endothelial cells is crucial for inflammatory reactions. Paracrine cross-talk and outside-in signaling (via adhesion molecules) have been characterized as communication pathways to date. As leukocytes and endothelial cells express connexins, we considered intercellular communication via gap junctions an intriguing additional concept. We found that gap-junctional coupling between neutrophils and endothelium occurred in a time-dependent, bidirectional manner and was facilitated by adhesion. After blockade of connexins, transmigration of neutrophils through the endothelial layer was enhanced, and the barrier function of cell monolayers was reduced during transmigration. Tumor necrosis factor α decreased coupling. In the presence of connexins, transmigration of neutrophils did not alter permeability. Thus, neutrophils couple to endothelium via gap junctions, functionally modulating transmigration and leakiness. Gapjunctional coupling may be a novel way of leukocyte- endothelial communication

Airfreight market in the Baltic countries : current development and future demand

Siirretty Doriast

Airfreight market in the Baltic countries : current development and future demand

Siirretty Doriast

A concept for integrated care pathways for atopic dermatitis — a GA2LEN ADCARE initiative

Introduction The integrated care pathways for atopic dermatitis (AD-ICPs) aim to bridge the gap between existing AD treatment evidence-based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co-ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems. Methods The GA2LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD-ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL2EN ADCARE centres. Results The AD-ICPs outline the diagnostic procedures, possible co-morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD. Conclusion The AD-ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD

Aesthetic manure : Strategies of new-right literary politics

Die Neue Rechte betreibt seit 2000 eine umfangreiche Literaturpolitik. Aktionen im Literaturbetrieb, eigene Publikationen sowie ein expandierender Literaturjournalismus (der neben Büchern und Zeitschriften auch Internetblogs, Podcasts und Videos umfasst) werden mit zunehmendem Geschick und Erfolg dazu genutzt, neurechte Ideologien im Kulturbetrieb zu verankern. Dies zeigte sich u.a. in der 2020 um die Schriftstellerin Monika Maron geführten Debatte, die der Aufsatz zum Ausgangspunkt nimmt, um die wichtigsten metapolitischen Strategien neurechter Literaturpolitik vorzustellen: eine Veränderung des Lektürekanons, eine politische Funktionalisierung von Ästhetik und ästhetischer Erziehung sowie literaturbetriebliche Aktionen. Abschließend wird am Streit um den Debutroman von Simon Strauß diskutiert, wie sich angemessen (auch literaturwissenschaftlich) auf neurechte Literaturpolitik reagieren lässt.Projekt DEA

Model predictive control of a collaborative manipulator considering dynamic obstacles

Collaborative robots have to adapt its motion plan to a dynamic environment and variation of task constraints. Currently, they detect collisions and interrupt or postpone their motion plan to prevent harm to humans or objects. The more advanced strategy proposed in this article uses online trajectory optimization to anticipate potential collisions, task variations, and to adapt the motion plan accordingly. The online trajectory planner pursues a model predictive control approach to account for dynamic motion objectives and constraints during task execution. The prediction model relates reference joint velocities to actual joint positions as an approximation of built-in robot tracking controllers. The optimal control problem is solved with direct collocation based on a hypergraph structure, which represents the nonlinear program and allows to efficiently adapt to structural changes in the optimization problem caused by moving obstacles. To demonstrate the effectiveness of the approach, the robot imitates pick-and-place tasks while avoiding self-collisions, semistatic, and dynamic obstacles, including a person. The analysis of the approach concerns computation time, constraint violations, and smoothness. It shows that after model identification, order reduction, and validation on the real robot, parallel integrators with compensation for input delays exhibit the best compromise between accuracy and computational complexity. The model predictive controller can successfully approach a moving target configuration without prior knowledge of the reference motion. The results show that pure hard constraints are not sufficient and lead to nonsmooth controls. In combination with soft constraints, which evaluate the proximity of obstacles, smooth and safe trajectories are planned

Two-way shape memory effect in (?+?) two-phase Co38Ni33Al29 single crystals

In the present study, it is shown that the aging in martensite under load is the effective way to create two-way shape memory effect at the martensite start temperature Ms=311 K with the reversible strain of 5 % along the [001]B2-direction in Co38Ni33Al29 single crystals with the minimum volume fraction fγ~1 % of large γ- phase precipitations. The increase of volume fraction up to fγ~5 % leads to the suppression of two-way shape memory effect, the reversible strain is less than 1 %