Glucocorticoid-Mediated Inhibition of Angiogenic Changes in Human Endothelial Cells Is Not Caused by Reductions in Cell Proliferation or Migration

Glucocorticoid-mediated inhibition of angiogenesis is important in physiology, pathophysiology and therapy. However, the mechanisms through which glucocorticoids inhibit growth of new blood vessels have not been established. This study addresses the hypothesis that physiological levels of glucocorticoids inhibit angiogenesis by directly preventing tube formation by endothelial cells.Cultured human umbilical vein (HUVEC) and aortic (HAoEC) endothelial cells were used to determine the influence of glucocorticoids on tube-like structure (TLS) formation, and on cellular proliferation (5-bromo-2'-deoxyuridine (BrdU) incorporation), viability (ATP production) and migration (Boyden chambers). Dexamethasone or cortisol (at physiological concentrations) inhibited both basal and prostaglandin F(2α) (PGF(2α))-induced and vascular endothelial growth factor (VEGF) stimulated TLS formation in endothelial cells (ECs) cultured on Matrigel, effects which were blocked with the glucocorticoid receptor antagonist RU38486. Glucocorticoids had no effect on EC viability, migration or proliferation. Time-lapse imaging showed that cortisol blocked VEGF-stimulated cytoskeletal reorganisation and initialisation of tube formation. Real time PCR suggested that increased expression of thrombospodin-1 contributed to glucocorticoid-mediated inhibition of TLS formation.We conclude that glucocorticoids interact directly with glucocorticoid receptors on vascular ECs to inhibit TLS formation. This action, which was conserved in ECs from two distinct vascular territories, was due to alterations in cell morphology rather than inhibition of EC viability, migration or proliferation and may be mediated in part by induction of thrombospodin-1. These findings provide important insights into the anti-angiogenic action of endogenous glucocorticoids in health and disease

Мотивационная политика предприятия как основа новой философии управления

В современной концепции управления ключевое место отводится человеку. Именно люди, характеризующиеся не только специальным образованием и профессиональными навыками, но и яркой индивидуальностью, способны генерировать новые идеи и решать непростые задачи в высококонкурентной и динамичной бизнес-среде. Такова закономерность в развитии экономических отношений и совершенствовании менеджмента организаций. Акценты в управлении компанией смещаются к идеологическим (культурным, духовным) ценностям предприятия, носителем которых является его персонал, конкретные сотрудники, способные в этих условиях обеспечивать эффективную работу в высококонкурентной среде

Osteoprotegerin reduces the development of pain behaviour and joint pathology in a model of osteoarthritis

Acknowledgements: OPG-Fc was a kind gift from Amgen Ltd. Funding: This work was supported by Arthritis Research UK, grant number 18769Peer reviewedPublisher PD

The correlation between radiative surface defect states and high color rendering index from ZnO nanotubes

Combined surface, structural and opto-electrical investigations are drawn from the chemically fashioned ZnO nanotubes and its heterostructure with p-GaN film. A strong correlation has been found between the formation of radiative surface defect states in the nanotubes and the pure cool white light possessing averaged eight color rendering index value of 96 with appropriate color temperature. Highly important deep-red color index value has been realized > 95 which has the capability to render and reproduce natural and vivid colors accurately. Diverse types of deep defect states and their relative contribution to the corresponding wavelengths in the broad emission band is suggested

The correlation between radiative surface defect states and high color rendering index from ZnO nanotubes

Combined surface, structural and opto-electrical investigations are drawn from the chemically fashioned ZnO nanotubes and its heterostructure with p-GaN film. A strong correlation has been found between the formation of radiative surface defect states in the nanotubes and the pure cool white light possessing averaged eight color rendering index value of 96 with appropriate color temperature. Highly important deep-red color index value has been realized > 95 which has the capability to render and reproduce natural and vivid colors accurately. Diverse types of deep defect states and their relative contribution to the corresponding wavelengths in the broad emission band is suggested

Deorbit kit demonstration mission

In Low Earth Orbit, it is possible to use the ambient plasma and the geomagnetic field to exchange momentum with the Earth's magnetosphere without using propellant. A device that allows an efficient momentum exchange is the electrodynamic tether (EDT), a long conductor attached to the satellite. EDT technology has been demonstrated in several past missions, being the Plasma Motor Generator mission (NASA 1993) one of the most successful. Nevertheless, it is not until today that reality has imposed a strong need and a concrete use case for developing this technology. In March 2019, the European Commission project Electrodynamic Tether technology for PAssive Consumable-less deorbit Kit (E.T.PACK) started the design of a new generation EDT. After completing the design phase, the consortium manufactured and is currently testing a Deorbit Kit Demonstrator (DKD) breadboard based on EDT technology. The objective of E.T.PACK is to reach Technology Readiness Level equal to 4 by 2022. The DKD is a standalone 24-kg satellite with the objective to demonstrate the performances of the improved EDT solution and validate its ultra-compact deployment system. The DKD is composed of two modules that will separate in orbit extending a 500-m long tape-like tether. The deployed bare-Aluminium tether will capture electrons from the ambient plasma passively and the circuit will be closed with the ionospheric plasma by using an active electron emitter. E.T.PACK tether will take advantage of several novelties with respect to the mission flown in the past that will allow to optimize the system volume and mass. Once successful demonstrated in orbit, the team plans to develop a suite of EDT systems capable of deorbiting satellites between 200 and 1000 kg from an altitude up to 1200 km in a few months. The work presents the current design status of the de-orbit kit demonstrator breadboard, the simulations of the system deorbit performances and the development approach.This work was supported by the European Union's Horizon 2020 Research and Innovation Programme under grant agreement No.828902 (3M€ E.T.PACK project) and No.101034874 (100K€ BMOM project). SG is supported by an Industrial Ph.D funded by Comunidad de Madrid (135K€ IND2019/TIC17198). The team has recently got 2.5M€ additional financial support from European Union (ETPACK-F project No. 101058166) for the manufacturing and qualification of the In Orbit Demonstration (IOD) by the end of 2025