Classifying Idiopathic Rapid Eye Movement Sleep Behavior Disorder, Controls, and Mild Parkinson\u27s Disease Using Gait Parameters

Background Subtle gait changes associated with idiopathic rapid eye movement sleep behavior disorder (iRBD) could allow early detection of subjects with future synucleinopathies. Objective The aim of this study was to create a multiclass model, using statistical learning from probability distribution of gait parameters, to distinguish between patients with iRBD, healthy control subjects (HCs), and patients with Parkinson\u27s disease (PD). Methods Gait parameters were collected in 21 participants with iRBD, 21 with PD, and 21 HCs, matched for age, sex, and education level. Lasso sparse linear regression explored gait features able to classify the three groups. Results The final model classified iRBD from HCs and from patients with PD equally well, with 95% accuracy, 100% sensitivity, and 90% specificity. Conclusions Gait parameters and a pretrained statistical model can robustly distinguish participants with iRBD from HCs and patients with PD. This could be used to screen subjects with future synucleinopathies in the general population and to identify a conversion threshold to PD. © 2022 International Parkinson and Movement Disorder Societ

BeatWalk: Personalized Music-Based Gait Rehabilitation in Parkinson’s Disease

Taking regular walks when living with Parkinson’s disease (PD) has beneficial effects on movement and quality of life. Yet, patients usually show reduced physical activity compared to healthy older adults. Using auditory stimulation such as music can facilitate walking but patients vary significantly in their response. An individualized approach adapting musical tempo to patients’ gait cadence, and capitalizing on these individual differences, is likely to provide a rewarding experience, increasing motivation for walk-in PD. We aim to evaluate the observance, safety, tolerance, usability, and enjoyment of a new smartphone application. It was coupled with wearable sensors (BeatWalk) and delivered individualized musical stimulation for gait auto-rehabilitation at home. Forty-five patients with PD underwent a 1-month, outdoor, uncontrolled gait rehabilitation program, using the BeatWalk application (30 min/day, 5 days/week). The music tempo was being aligned in real-time to patients’ gait cadence in a way that could foster an increase up to +10% of their spontaneous cadence. Open-label evaluation was based on BeatWalk use measures, questionnaires, and a six-minute walk test. Patients used the application 78.8% (±28.2) of the prescribed duration and enjoyed it throughout the program. The application was considered “easy to use” by 75% of the patients. Pain, fatigue, and falls did not increase. Fear of falling decreased and quality of life improved. After the program, patients improved their gait parameters in the six-minute walk test without musical stimulation. BeatWalk is an easy to use, safe, and enjoyable musical application for individualized gait rehabilitation in PD. It increases “walk for exercise” duration thanks to high observance.This research was supported by a European grant: BeatHealth: Health and Wellness on the Beat for VC, DD, CL, AGi, VD, RV, EH, ED, ML, BB, and SB (EU FP7-ICT contract #610633)

Study of the autophagy pathway in the Pacific oyster, Crassostrea gigas, in response to an infection by the virus OsHV-1

Les importantes mortalités observées sur le naissain de l’huître creuse, Crassostrea gigas, ont fortement affecté l’économie aquacole de plusieurs pays dans le monde. Les causes de ces mortalités sont complexes, mais un agent viral appartenant à la famille des herpèsvirus, appelé ostreid herpesvirus 1 (OsHV-1), a été identifié comme étant le principal facteur responsable de ces mortalités. Les moyens disponibles pour lutter contre le virus OsHV-1 restent limités et une meilleure connaissance des interactions entre l’huître creuse et le virus est nécessaire. Récemment, les résultats de plusieurs études et la caractérisation du génome de C. gigas ont démontré l’existence potentielle chez cette espèce de plusieurs voies antivirales connues chez les mammifères. La voie de l’autophagie est impliquée dans de nombreux processus cellulaires dont la défense immunitaire. Cette voie serait fonctionnelle dans le manteau de C. gigas et impliquée dans la réponse de l’huître creuse à différentes pathologies incluant les infections virales. Dans le cadre de la thèse, un travail a été réalisé afin d’approfondir les connaissances sur le mécanisme de l’autophagie chez C. gigas et sur sa régulation au cours d’une infection par le virus OsHV-1. Ces travaux de thèse ont permis de mettre en évidence une forte conservation de la voie de l’autophagie au niveau moléculaire. Pour la première fois chez C. gigas, il a été observé des structures autophagiques chez les hémocytes. Ce résultat a permis de développer de nouvelles approches afin de détecter et suivre la régulation de l’autophagie chez l’huître creuse. Un suivi de l’autophagie au cours d’une infection par le virus OsHV-1 a montré une réplication virale suivie d’une modulation de l’autophagie dans le manteau et dans l’hémolymphe. Enfin, il a été montré une régulation différentielle de l’autophagie au niveau transcriptiomique dans le manteau et dans l’hémolymphe.Mortality outbreaks of young Pacific oysters, Crassostrea gigas, have seriously affected the aquaculture economy in several countries around the world. Although the causes for these mortalities outbreaks are complex, a viral agent was identified as the main factor, the ostreid herpesvirus 1 (OsHV-1). The mean to fight against the virus remains limited and Pacific oyster/virus interactions need to be further investigated. Recently, the results of several studies and the C. gigas genome sequencing have demonstrated the potential existence of several known mammals’ antiviral pathways in the Pacific oyster. The autophagy pathway is involved in many cellular processes including immune defense. This pathway seems to be functional in the mantle of C. gigas and involve in the response of the Pacific oyster to several pathologies including viral diseases. As part of this Phd work was to improve knowledge about the autophagy pathway mechanism in C. gigas and to decipher it modulation during the process of an infection by the virus OsHV-1. This work has highlighted a strong conservation of the pathway of autophagy at the molecular level. For the first time in C. gigas, autophagic structures were observed in haemocytes. This result has allowed to development new approaches to detect and monitor the regulation of autophagy in Pacific oyster. A monitoring of autophagy during an infection by the virus OsHV-1 showed that the viral replication is followed by a modulation of autophagy in the mantle and in haemolymph. Finally, a differential regulation of the autophagy pathway at the transcriptomic level in the mantle and haemolymph has been shown

Caractérisation de la voie de l’autophagie chez l’huître creuse Crassostrea gigas en réponse à une infection par le virus OsHV-1

Mortality outbreaks of young Pacific oysters, Crassostrea gigas, have seriously affected the aquaculture economy in several countries around the world. Although the causes for these mortalities outbreaks are complex, a viral agent was identified as the main factor, the ostreid herpesvirus 1 (OsHV-1). The mean to fight against the virus remains limited and Pacific oyster/virus interactions need to be further investigated. Recently, the results of several studies and the C. gigas genome sequencing have demonstrated the potential existence of several known mammals’ antiviral pathways in the Pacific oyster. The autophagy pathway is involved in many cellular processes including immune defense. This pathway seems to be functional in the mantle of C. gigas and involve in the response of the Pacific oyster to several pathologies including viral diseases. As part of this Phd work was to improve knowledge about the autophagy pathway mechanism in C. gigas and to decipher it modulation during the process of an infection by the virus OsHV-1. This work has highlighted a strong conservation of the pathway of autophagy at the molecular level. For the first time in C. gigas, autophagic structures were observed in haemocytes. This result has allowed to development new approaches to detect and monitor the regulation of autophagy in Pacific oyster. A monitoring of autophagy during an infection by the virus OsHV-1 showed that the viral replication is followed by a modulation of autophagy in the mantle and in haemolymph. Finally, a differential regulation of the autophagy pathway at the transcriptomic level in the mantle and haemolymph has been shown.Les importantes mortalités observées sur le naissain de l’huître creuse, Crassostrea gigas, ont fortement affecté l’économie aquacole de plusieurs pays dans le monde. Les causes de ces mortalités sont complexes, mais un agent viral appartenant à la famille des herpèsvirus, appelé ostreid herpesvirus 1 (OsHV-1), a été identifié comme étant le principal facteur responsable de ces mortalités. Les moyens disponibles pour lutter contre le virus OsHV-1 restent limités et une meilleure connaissance des interactions entre l’huître creuse et le virus est nécessaire. Récemment, les résultats de plusieurs études et la caractérisation du génome de C. gigas ont démontré l’existence potentielle chez cette espèce de plusieurs voies antivirales connues chez les mammifères. La voie de l’autophagie est impliquée dans de nombreux processus cellulaires dont la défense immunitaire. Cette voie serait fonctionnelle dans le manteau de C. gigas et impliquée dans la réponse de l’huître creuse à différentes pathologies incluant les infections virales. Dans le cadre de la thèse, un travail a été réalisé afin d’approfondir les connaissances sur le mécanisme de l’autophagie chez C. gigas et sur sa régulation au cours d’une infection par le virus OsHV-1. Ces travaux de thèse ont permis de mettre en évidence une forte conservation de la voie de l’autophagie au niveau moléculaire. Pour la première fois chez C. gigas, il a été observé des structures autophagiques chez les hémocytes. Ce résultat a permis de développer de nouvelles approches afin de détecter et suivre la régulation de l’autophagie chez l’huître creuse. Un suivi de l’autophagie au cours d’une infection par le virus OsHV-1 a montré une réplication virale suivie d’une modulation de l’autophagie dans le manteau et dans l’hémolymphe. Enfin, il a été montré une régulation différentielle de l’autophagie au niveau transcriptiomique dans le manteau et dans l’hémolymphe

Identification of the autophagy pathway in a mollusk bivalve, Crassostrea gigas

The Pacific oyster, Crassostrea gigas, is a mollusk bivalve commercially important as a food source. Pacific oysters are subjected to stress and diseases during culture. The autophagy pathway is involved in numerous cellular processes, including responses to starvation, cell death, and microorganism elimination. Autophagy also exists in C. gigas, and plays a role in the immune response against infections. Although this process is well-documented and conserved in most animals, it is still poorly understood in mollusks. To date, no study has provided a complete overview of the molecular mechanism of autophagy in mollusk bivalves. In this study, human and yeast ATG protein sequences and public databases (Uniprot and NCBI) were used to identify protein members of the C. gigas autophagy pathway. A total of 35 autophagy related proteins were found in the Pacific oyster. RACE-PCR was performed on several genes. Using molecular (real-time PCR) and protein-based (western blot and immunohistochemistry) approaches, the expression and localization of ATG12, ATG9, BECN1, MAP1LC3, MTOR, and SQSTM1, was investigated in different tissues of the Pacific oyster. Comparison with human and yeast counterparts demonstrated a high homology with the human autophagy pathway. The results also demonstrated that the key autophagy genes and their protein products were expressed in all the analyzed tissues of C. gigas. This study allows the characterization of the complete C. gigas autophagy pathway for the first time. Abbreviations: ATG: autophagy related; Atg1/ULK: unc-51 like autophagy activating kinase; ATG7: autophagy related 7; ATG9: autophagy related 9; ATG12: autophagy related 12; BECN1: beclin 1; BSA: bovine serum albumin; cDNA: complementary deoxyribonucleic acid; DNA: deoxyribonucleic acid; GABARAP: GABA type A receptor-associated protein; IHC: immunohistochemistry; MAP1LC3/LC3/Atg8: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; NCBI: national center for biotechnology information; ORF: open reading frame; PBS: phosphate-buffered saline; PCR: polymerase chain reaction; PtdIns3K: class III phosphatidylinositol 3-kinase; RACE-PCR: rapid amplification of cDNA-ends by polymerase chain reaction; RNA: ribonucleic acid; SQSTM1: sequestosome 1; Uniprot: universal protein resource; WIPI: WD repeat domain, phosphoinositide interacting

Monitoring Autophagy at Cellular and Molecular Level in Crassostrea gigas During an Experimental Ostreid Herpesvirus 1 (OsHV-1) Infection

Mortality outbreaks of young Pacific oysters, Crassostrea gigas, have seriously affected the oyster-farming economy in several countries around the world. Although the causes of these mortality outbreaks appear complex, a viral agent has been identified as the main factor: a herpesvirus called ostreid herpesvirus 1 (OsHV-1). Autophagy is an important degradation pathway involved in the response to several pathologies including viral diseases. In C. gigas, recent studies indicate that this pathway is conserved and functional in at least haemocytes and the mantle. Furthermore, an experimental infection in combination with compounds known to inhibit or induce autophagy in mammals revealed that autophagy is involved in the response to OsHV-1 infection. In light of these results, the aim of this study was to determine the role of autophagy in the response of the Pacific oyster to infection by virus OsHV-1. For this purpose, an experimental infection in combination with a modulator of autophagy was performed on Pacific oysters known to have intermediate susceptibility to OsHV-1 infection. In haemolymph and the mantle, the autophagy response was monitored by flow cytometry, western blotting, and real-time PCR. At the same time, viral infection was evaluated by quantifying viral DNA and RNA amounts by real-time PCR. Although the results showed activation of autophagy in haemolymph and the mantle 14 hours post infection (after viral replication was initiated), they were also indicative of different regulatory mechanisms of autophagy in the two tissues, thus supporting an important function of autophagy in the response to virus OsHV-1

A study of autophagy in hemocytes of the Pacific oyster, Crassostrea gigas

Macroautophagy is a mechanism that is involved in various cellular processes, including cellular homeostasis and innate immunity. This pathway has been described in organisms ranging in complexity from yeasts to mammals, and recent results indicate that it occurs in the mantle of the Pacific oyster, Crassostrea gigas. However, the autophagy pathway has never been explored in the hemocytes of C. gigas, which are the main effectors of its immune system and thus play a key role in the defence of the Pacific oyster against pathogens. To investigate autophagy in oyster hemocytes, tools currently used to monitor this mechanism in mammals, including flow cytometry, fluorescent microscopy and transmission electron microscopy, were adapted and applied to the hemocytes of the Pacific oyster. Oysters were exposed for 24 and 48 h to either an autophagy inducer (carbamazepine, which increases the production of autophagosomes) or an autophagy inhibitor (ammonium chloride, which prevents the degradation of autophagosomes). Autophagy was monitored in fresh hemocytes withdrawn from the adductor muscles of oysters using a combination of the three aforementioned methods. We successfully labelled autophagosomes and observed them by flow cytometry and fluorescence microscopy, and then used electron microscopy to observe ultrastructural modifications related to autophagy, including the presence of double-membrane-bound vacuoles. Our results demonstrated that autophagy occurs in hemocytes of C. gigas and can be modulated by molecules known to modulate autophagy in other organisms. This study describes an integrated approach that can be applied to investigate autophagy in marine bivalves at the cellular level

Evidence of the bioaccumulation of ciguatoxins in giant clams (Tridacna maxima) exposed to Gambierdiscus spp. cells

Ciguatera Fish Poisoning (CFP) is a foodborne disease classically related to the consumption of tropical coral reef fishes contaminated with ciguatoxins (CTXs), neurotoxins produced by dinoflagellates of the Gambierdiscus genus. Severe atypical ciguatera-like incidents involving giant clams, a marine resource highly consumed in the South Pacific, are also frequently reported in many Pacific Islands Countries and Territories. The present study was designed to assess the ability of giant clams to accumulate CTXs in their tissues and highlight the potential health risks associated with their consumption. Since giant clams are likely to be exposed to both free-swimming Gambierdiscus cells and dissolved CTXs in natural environment, ex situ contamination experiments were conducted as follows: giant clams were exposed to live or lyzed cells of TB92, a highly toxic strain of G. polynesiensis containing 5.83 ± 0.85 pg P-CTX-3C equiv. cell−1vs. HIT0, a weakly toxic strain of G. toxicus containing only (2.05 ± 1.16) × 10−3 pg P-CTX-3C equiv. cell−1, administered over a 48 h period at a concentration of 150 cells mL−1. The presence of CTXs in giant clams tissues was further assessed using the mouse neuroblastoma cell-based assay (CBA-N2a). Results showed that giant clams exposed to either lyzed or live cells of TB92 were able to bioaccumulate CTXs at concentrations well above the safety limit recommended for human consumption, i.e. 3.28 ± 1.37 and 2.92 ± 1.03 ng P-CTX-3C equiv. g−1 flesh (wet weight), respectively, which represented approximately 3% of the total toxin load administered to the animals. In contrast, giant clams exposed to live or lyzed cells of HIT0 were found to be free of toxins, suggesting that in the nature, the risk of contamination of these bivalves is established only in the presence of highly toxic blooms of Gambierdiscus. Liquid chromatography–mass spectrometry (LC–MS/MS) analyses confirmed CBA-N2a results and also revealed that P-CTX-3B was the major CTX congener retained in the tissues of giant clams fed with TB92 cells. To the best of our knowledge, this study is the first to provide evidence of the bioaccumulation of Gambierdiscus CTXs in giant clams and confirms that these bivalve molluscs can actually constitute another pathway in ciguatera poisonings. While most monitoring programs currently focus on fish toxicity, these findings stress the importance of a concomitant surveillance of these marine invertebrates in applicable locations for an accurate assessment of ciguatera risk

Classifying Idiopathic Rapid Eye Movement Sleep Behavior Disorder, Controls, and Mild Parkinson's Disease Using Gait Parameters

International audienceBackgroundSubtle gait changes associated with idiopathic rapid eye movement sleep behavior disorder (iRBD) could allow early detection of subjects with future synucleinopathies.ObjectiveThe aim of this study was to create a multiclass model, using statistical learning from probability distribution of gait parameters, to distinguish between patients with iRBD, healthy control subjects (HCs), and patients with Parkinson's disease (PD).MethodsGait parameters were collected in 21 participants with iRBD, 21 with PD, and 21 HCs, matched for age, sex, and education level. Lasso sparse linear regression explored gait features able to classify the three groups.ResultsThe final model classified iRBD from HCs and from patients with PD equally well, with 95% accuracy, 100% sensitivity, and 90% specificity.ConclusionsGait parameters and a pretrained statistical model can robustly distinguish participants with iRBD from HCs and patients with PD. This could be used to screen subjects with future synucleinopathies in the general population and to identify a conversion threshold to PD