University of Geneva

About: University of Geneva is a education organization based out in Geneva, Switzerland. It is known for research contribution in the topics: Population & Galaxy. The organization has 26887 authors who have published 65265 publications receiving 2931373 citations. The organization is also known as: Geneva University & Universite de Geneve.

Amiloride inhibits macropinocytosis by lowering submembranous pH and preventing Rac1 and Cdc42 signaling

Abstract: Macropinocytosis is differentiated from other types of endocytosis by its unique susceptibility to inhibitors of Na+/H+ exchange. Yet, the functional relationship between Na+/H+ exchange and macropinosome formation remains obscure. In A431 cells, stimulation by EGF simultaneously activated macropinocytosis and Na+/H+ exchange, elevating cytosolic pH and stimulating Na+ influx. Remarkably, although inhibition of Na+/H+ exchange by amiloride or HOE-694 obliterated macropinocytosis, neither cytosolic alkalinization nor Na+ influx were required. Instead, using novel probes of submembranous pH, we detected the accumulation of metabolically generated acid at sites of macropinocytosis, an effect counteracted by Na+/H+ exchange and greatly magnified when amiloride or HOE-694 were present. The acidification observed in the presence of the inhibitors did not alter receptor engagement or phosphorylation, nor did it significantly depress phosphatidylinositol-3-kinase stimulation. However, activation of the GTPases that promote actin remodelling was found to be exquisitely sensitive to the submembranous pH. This sensitivity confers to macropinocytosis its unique susceptibility to inhibitors of Na+/H+ exchange.

Reactive oxygen species: from health to disease.

Abstract: Upon reaction with electrons, oxygen is transformed into reactive oxygen species (ROS). It has long been known that ROS can destroy bacteria and destroy human cells, but research in recent decades has highlighted new roles for ROS in health and disease. Indeed, while prolonged exposure to high ROS concentrations may lead to non-specific damage to proteins, lipids, and nucleic acids, low to intermediate ROS concentrations exert their effects rather through regulation of cell signalling cascades. Biological specificity is achieved through the amount, duration, and localisation of ROS production. ROS have crucial roles in normal physiological processes, such as through redox regulation of protein phosphorylation, ion channels, and transcription factors. ROS are also required for biosynthetic processes, including thyroid hormone production and crosslinking of extracellular matrix. There are multiple sources of ROS, including NADPH oxidase enzymes; similarly, there are a large number of ROS-degrading systems. ROS-related disease can be either due to a lack of ROS (e.g., chronic granulomatous disease, certain autoimmune disorders) or a surplus of ROS (e.g., cardiovascular and neurodegenerative diseases). For diseases caused by a surplus of ROS, antioxidant supplementation has proven largely ineffective in clinical studies, most probably because their action is too late, too little, and too non-specific. Specific inhibition of ROS-producing enzymes is an approach more promising of clinical efficacy.

Chitosan: A Unique Polysaccharide for Drug Delivery

Abstract: The aim of this review is to give an insight into the many potential applications of chitosan as a pharmaceutical drug carrier. The first part of this review concerns the principal uses of chitosan as an excipient in oral formulations (particularly as a direct tableting agent) and as a vehicle for parenteral drug delivery devices. The use of chitosan to manufacture sustained-release systems deliverable by other routes (nasal, ophthalmic, transdermal, and implantable devices) is discussed in the second part.

Weak ergodicity breaking from quantum many-body scars

Abstract: The thermodynamic description of many-particle systems rests on the assumption of ergodicity, the ability of a system to explore all allowed configurations in the phase space. Recent studies on many-body localization have revealed the existence of systems that strongly violate ergodicity in the presence of quenched disorder. Here, we demonstrate that ergodicity can be weakly broken by a different mechanism, arising from the presence of special eigenstates in the many-body spectrum that are reminiscent of quantum scars in chaotic non-interacting systems. In the single-particle case, quantum scars correspond to wavefunctions that concentrate in the vicinity of unstable periodic classical trajectories. We show that many-body scars appear in the Fibonacci chain, a model with a constrained local Hilbert space that has recently been experimentally realized in a Rydberg-atom quantum simulator. The quantum scarred eigenstates are embedded throughout the otherwise thermalizing many-body spectrum but lead to direct experimental signatures, as we show for periodic recurrences that reproduce those observed in the experiment. Our results suggest that scarred many-body bands give rise to a new universality class of quantum dynamics, opening up opportunities for the creation of novel states with long-lived coherence in systems that are now experimentally realizable.