Search results for "Mechanism"

Galantamine is an allosterically potentiating ligand of the human α4/β2 nAChR

2000

Galantamine (ReminyI ) is a novel drug treatment for mild to moderate Alzheimer's disease (AD). Originally established as a reversible inhibitor of the acetylcholine-degrading enzyme acetylcholinesterase (AChE), galantamine also acts as an allosterically potentiating ligand (APL) on nicotinic acetylcholine receptors (nAChR). Having previously established this second mode of action on nAChRs from murine brain, we demonstrate here the same action of galantamine on the most abundant nAChR in the human brain, the α4/β2 subtype. This nAChR-sensitizing action is not a common property of all, or most, AChE inhibitors, as is shown by the absence of this effect for other therapeutically applied AChE…

Directional Shuttling of a Stimuli-Responsive Cone-Like Macrocycle on a Single-State Symmetric Dumbbell Axle

2018

Rotaxane-based molecular shuttles are often operated using low-symmetry axles and changing the states of the binding stations. A molecular shuttle capable of directional shuttling of an acid-responsive cone-like macrocycle on a single-state symmetric dumbbell axle is now presented. The axle contains three binding stations: one symmetric di(quaternary ammonium) station and two nonsymmetric phenyl triazole stations arranged in opposite orientations. Upon addition of an acid, the protonated macrocycle shuttles from the di(quaternary ammonium) station to the phenyl triazole binding station closer to its butyl groups. This directional shuttling presumably originates from charge repulsion and an …

Known knowns and known unknowns on behavior change interventions and mechanisms of action.

2020

Systematic reviews and meta-analyses of research play an important role in summarizing current knowledge on the efficacy of the behavior change techniques and mechanisms of action that comprise behavioral interventions. The current reviews in the science of behavior change (SOBC) special issue represent a ‘step change’ in evaluating current evidence on behavior change interventions and mechanisms. This concluding article outlines the key findings and emerging issues identified in the reviews (‘known knowns’), and summarizes the evidence gaps highlighted by the reviews that need to be addressed in future research (‘known unknowns’). Specifically, findings of the reviews indicate that: tests …

Cognitive emotion regulation withstands the stress test: An fMRI study on the effect of acute stress on distraction and reappraisal

2021

Cognitive emotion regulation is a key mechanism for the maintenance of mental health, but may fail, when individuals are exposed to acute stress. To date, it is not well understood whether and to what extent acute stress effects contribute to impairments in emotion regulation capacities as the sparse existing studies have yielded heterogeneous results, indicating that stress timing might be a crucial factor.In the present study, 81 healthy participants underwent either an acute stress task (ScanSTRESS-C; n = 40) or a control condition (n = 41) while lying in the MRI scanner. In the subsequent Cognitive Emotion Regulation Task (CERT), participants were confronted with neutral or negative pic…

Specific Recognition of the 5′-Untranslated Region of West Nile Virus Genome by Human Innate Immune System

2022

In the last few years, the sudden outbreak of COVID-19 caused by SARS-CoV-2 proved the crucial importance of understanding how emerging viruses work and proliferate, in order to avoid the repetition of such a dramatic sanitary situation with unprecedented social and economic costs. West Nile Virus is a mosquito-borne pathogen that can spread to humans and induce severe neurological problems. This RNA virus caused recent remarkable outbreaks, notably in Europe, highlighting the need to investigate the molecular mechanisms of its infection process in order to design and propose efficient antivirals. Here, we resort to all-atom Molecular Dynamics simulations to characterize the structure of th…

New seismological, structural and marine geology constraints for a seismotectonic model of the hinge zone between northern Sicily and southern Tyrrhe…

2013

Change of Direction Biomechanics in a 180-Degree Pivot Turn and the Risk for Noncontact Knee Injuries in Youth Basketball and Floorball Players.

2021

Background: Studies investigating biomechanical risk factors for knee injuries in sport-specific tasks are needed. Purpose: To investigate the association between change of direction (COD) biomechanics in a 180-degree pivot turn and knee injury risk among youth team sport players. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 258 female and male basketball and floorball players (age range, 12-21 years) participated in the baseline COD test and follow-up. Complete data were obtained from 489 player-legs. Injuries, practice, and game exposure were registered for 12 months. The COD test consisted of a quick ball pass before and after a high-speed 180-degree pivot turn o…

Expression of yeast but not human apurinic/apyrimidinic endonuclease renders Chinese hamster cells more resistant to DNA damaging agents.

1997

Abasic sites represent ubiquitous DNA lesions that arise spontaneously or are induced by DNA-damaging agents. They block DNA replication and are considered to be cytotoxic and mutagenic. The key enzymes involved in the repair of abasic sites are apurinic/apyrimidinic (AP) endonucleases which process these lesions in an error-free mechanism. To analyze the role of AP endonuclease in the protection of mammalian cells against DNA damaging agents, we have transfected both the human (APE) and the yeast (APN1) AP endonuclease in Chinese hamster cells and compared the effects of expression of these genes in stable transfectants as to survival of cells and formation of chromosomal aberrations. Alth…

Characterization of the Viable but Nonculturable (VBNC) State in Saccharomyces cerevisiae

2013

The Viable But Non Culturable (VBNC) state has been thoroughly studied in bacteria. In contrast, it has received much less attention in other microorganisms. However, it has been suggested that various yeast species occurring in wine may enter in VBNC following sulfite stress.In order to provide conclusive evidences for the existence of a VBNC state in yeast, the ability of Saccharomyces cerevisiae to enter into a VBNC state by applying sulfite stress was investigated. Viable populations were monitored by flow cytometry while culturable populations were followed by plating on culture medium. Twenty-four hours after the application of the stress, the comparison between the culturable populat…

Regulation of mating in the budding yeast Saccharomyces cerevisiae by the zinc cluster proteins Sut1 and Sut2

2013

This article is made available through the Brunel Open Access Publishing Fund. Copyright @ The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The zinc cluster proteins Sut1 and Sut2 play a role in sterol uptake and filamentous growth in the budding yeast Saccharomyces cerevisiae. In this study, we show that they are also involved in mating. Cells that lack both SUT1 and SUT2 were defective in mating. The expression of the genes NCE102 and PRR2 was increased in the sut1 sut2 double deletion mutant…