How the central domain of dystrophin acts to bridge F-actin to sarcolemmal lipids

Dystrophin is a large intracellular protein that prevents sarcolemmal ruptures by providing a mechanical link between the intracellular actin cytoskeleton and the transmembrane dystroglycan complex. Dystrophin deficiency leads to the severe muscle wasting disease Duchenne Muscular Dystrophy and the milder allelic variant, Becker Muscular Dystrophy (DMD and BMD). Previous work has shown that concomitant interaction of the actin binding domain 2 (ABD2) comprising spectrin like repeats 11 to 15 (R11-15) of the central domain of dystrophin, with both actin and membrane lipids, can greatly increase membrane stiffness. Based on a combination of SAXS and SANS measurements, mass spectrometry analysis of cross-linked complexes and interactive low-resolution simulations, we explored in vitro the molecular properties of dystrophin that allow the formation of ABD2-F-actin and ABD2-membrane model complexes. In dystrophin we identified two subdomains interacting with F-actin, one located in R11 and a neighbouring region in R12 and another one in R15, while a single lipid binding domain was identified at the C-terminal end of R12. Relative orientations of the dystrophin central domain with F-actin and a membrane model were obtained from docking simulation under experimental constraints. SAXS-based models were then built for an extended central subdomain from R4 to R19, including ABD2. Overall results are compatible with a potential F-actin/dystrophin/membrane lipids ternary complex. Our description of this selected part of the dystrophin associated complex bridging muscle cell membrane and cytoskeleton opens the way to a better understanding of how cell muscle scaffolding is maintained through this essential protein

Artificial intelligence in biological activity prediction

Artificial intelligence has become an indispensable resource in chemoinformatics. Numerous machine learning algorithms for activity prediction recently emerged, becoming an indispensable approach to mine chemical information from large compound datasets. These approaches enable the automation of compound discovery to find biologically active molecules with important properties. Here, we present a review of some of the main machine learning studies in biological activity prediction of compounds, in particular for sweetness prediction. We discuss some of the most used compound featurization techniques and the major databases of chemical compounds relevant to these tasks.This study was supported by the European Commission through project SHIKIFACTORY100 - Modular cell factories for the production of 100 compounds from the shikimate pathway (Reference 814408), and by the Portuguese FCT under the scope of the strategic funding of UID/BIO/04469/2019 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020.info:eu-repo/semantics/publishedVersio

A united statement of the global chiropractic research community against the pseudoscientific claim that chiropractic care boosts immunity.

BACKGROUND: In the midst of the coronavirus pandemic, the International Chiropractors Association (ICA) posted reports claiming that chiropractic care can impact the immune system. These claims clash with recommendations from the World Health Organization and World Federation of Chiropractic. We discuss the scientific validity of the claims made in these ICA reports. MAIN BODY: We reviewed the two reports posted by the ICA on their website on March 20 and March 28, 2020. We explored the method used to develop the claim that chiropractic adjustments impact the immune system and discuss the scientific merit of that claim. We provide a response to the ICA reports and explain why this claim lacks scientific credibility and is dangerous to the public. More than 150 researchers from 11 countries reviewed and endorsed our response. CONCLUSION: In their reports, the ICA provided no valid clinical scientific evidence that chiropractic care can impact the immune system. We call on regulatory authorities and professional leaders to take robust political and regulatory action against those claiming that chiropractic adjustments have a clinical impact on the immune system

Effects of perceived cost, service quality, and customer satisfaction on health insurance service continuance

This paper aims to contribute to the universal discourse on financial services continuance behavior by examining the impact of service cost on customers\u27 service-quality perception and service continuance intention. It presents the results of an empirical study that has explored the impacts of service cost, service quality, and customer satisfaction on health insurance customers\u27 behavioral intention toward continuing or discontinuing with their service providers. Very few studies had examined the impact of service cost on service-quality perception. Our study attempts to fill that gap. A sample of 820 customers was surveyed, and 624 usable responses were analyzed with ANOVA, standard multiple regression, and logistic regression. Our findings indicate that, although highly satisfied health insurance customers will most likely retain their current service providers, customer dissatisfaction does not necessarily lead to discontinuance. Our results also provide some operational implications for health insurance managers, with strategies for reducing attrition and improving customer retention

Improvement of the Spatial Amplitude Isotropy of a 4^4He Magnetometer Using a Modulated Pumping Beam

Optically pumped magnetometers are scalar magnetometers. Contrary to vectoriel magnetometers, they measure the total magnetic field whatever the direction of the sensor. However, for some orientations of the magnetometer with respect to the magnetic field direction, the resonant signal vanishes and the measurement is impossible. In this paper we present a simple solution to reduce the amplitude spatial anisotropy and apply it to a $^4$He magnetometer developed in our Laboratory.Les magnétomètres à pompage optique sont des magnétomètres scalaires. Contrairement aux magnétomètres vectoriels, ils mesurent le module du champ magnétique quelle que soit l'orientation du capteur dans l'espace. Cependant, pour certaines orientations du magnétomètre par rapport à la direction du champ à mesurer, l'amplitude du signal de résonance s'annule et la mesure devient impossible. Dans cet article, nous présentons une solution simple pour réduire l'anisotropie spatiale d'amplitude et nous l'appliquons à un magnétomètre à hélium-4 développé dans notre Laboratoire

4^4He Optical Pumping with Frequency Modulated Light

Recently a distributed Bragg reflection (DBR) laser diode was commercialised by SDL (USA) for helium optical pumping experiments. An interesting feature of the new device is the possibility of frequency modulation of the diode output by modulating the current intensity, leading to a new pumping scheme called optical pumping with frequency modulated light. We develop this method to induce spin precession and obtain new resonances in $^4$He atomic gas, simply by modulating the frequency of the pumping light at the Larmor frequency of atomic states in a static magnetic field. These resonances are analysed with a simple model taking into account velocity changing collisions.Depuis avril 1994, une diode laser monomode à 1.083 $\mu$m est commercialisée par SDL (USA) pour des expériences de pompage optique de l'hélium. L'utilisation d'un laser à semi-conducteur permet de moduler facilement la longueur d'onde d'émission. Ceci nous a permis d'expérimenter un nouveau type de pompage, le pompage optique en modulation de fréquence. Nous développons cette méthode pour induire une précession forcée des spins électroniques des atomes d'hélium-4: on observe de nouveaux signaux de résonance en modulant la fréquence de la lumière émise à la fréquence de Larmor des atomes placés dans un champ magnétique statique. Ces signaux sont confrontés à un modèle simple prenant en compte les collisions de changement de vitesse.

Measurements of the Nuclear Polarisation of Optically Pumped 3{^{3}}He Atoms Using a 4{^{4}}He Magnetometer

A $^{4}$He magnetometer is used to detect the static magnetic field produced by optically pumped $^{3}$He nuclei submitted to a RF discharge. The experiment is made in a magnetic field whose value (40 $\mu$T) is close to the earth field value. From this measurement, we determine the $^{3}$He nuclear polarisation $P_{\rm n}$. For comparison, simultaneous determination of $P_{\rm n}$ is made by measuring the degree of circular polarisation of one of the fluorescence lines emitted from the discharge.Nous utilisons un magnétomètre à hélium-4 pour détecter le champ magnétique statique créé par les spins nucléaires d'atomes hélium-3 soumis à décharge et orientés par pompage optique. L'expérience est réalisée dans un champ magnétique directeur voisin de 40 $\mu$T (valeur voisine du champ terrestre). À partir de cette mesure, nous déterminons la polarisation nucléaire $P_{\rm n}$ du gaz. Simultanément, nous comparons ce résultat à celui obtenu en mesurant $P_{\rm n}$ par le degré de polarisation circulaire d'une raie de fluorescence émise par la décharge

Application of the Optogalvanic Detection Technique to the 4He\mathsf{^{4}He} Magnetometer

The optogalvanic detection of the magnetic resonance on the Helium ($2^{3}$S$_{1}$) metastable state is investigated in view of its application to $^{4}$He magnetometers. Metastable atoms are optically pumped with an intensity modulated beam and resonance signals are measured versus geometrical such as light polarization and magnetic field orientations