The FOVEAL project aims at developing a novel theoretical framework for understanding the muscle force production capacity as a function of time and contraction velocity during animal locomotion. This project rely on a multidisciplinary research team including specialists in applied mathematics, muscle biology, integrative physiology, biomechanics and ecology. We will first propose a mathematical model that describes the force-velocity-endurance capacity. This relation will make possible to understand the animal locomotion capacities when the mechanical constraints are variable (e.g. in mountains). As this relation seems valid from the organ (muscle) to the function (locomotion) and across species, the proposed approach originality is to take advantage of different experimental models (scales and species) to address the different research questions. Thus, in situ muscle mice model will provide insight at the muscle level thanks to functional, histological and biochemical analysis; running human model is the cornerstone as it allows to test our hypothesis and validate the methodological approach in both laboratory-controlled conditions (running treadmill) and natural environment (trail running). Integrative exercise physiology approach will also be possible in humans to understand the mechanisms involved in the individual force-velocity-endurance characteristics Finally, wild chamois model will permit to develop a non-invasive evaluation methodology of wild animals in their natural environment presenting variable mechanical conditions. This will provide insights in the relationships between the muscle organ and the locomotor function, and between the capacities of individuals and the requirements of the physical activity being health/performance (human) or survival (animals).

Theoretical framework Motor sequence learning requires repeated practice, which may be exhausting for older adults, especially during rehabilitation. Among less physically demanding interventions to preserve/enhance motor functions in elderly people, motor imagery (MI) training has gained attention. However, we do not know whether MI training might benefit from sleep in older adults, as shown in young adults. Research questions This project will focus on four research questions: (1) Does acquisition of a fine and a gross motor task supported by MI training differ between young and older adults? (2) Does the effects of sleep versus wakefulness on consolidation after MI training differ between these tasks and age groups? (3) How does EEG activity (mu rhythm; 7-13Hz) during MI of these two tasks differ from rest, and does it change after learning in the two populations? (4) How is EEG activity (sleep spindle, slow wave activity) during sleep associated with the consolidation process of the two tasks and in the two age groups? Methods We will test 120 young (20-35 years) and 120 older adults (65-80 years). Their sleep-wake cycle will be monitored with sleep logs and actigraphy for one week. Polysomnography will be recorded during an adaptation night and during the night following training. A classical finger-tapping task (FTT), and a new whole-body task (WBT) will be used. Within each population (young, older) participants will be randomly assigned (six groups) to one of two tasks (FTT, WBT), training conditions (MI training, no-training) and times of the day (AM, PM). Training will be either followed by a consolidation interval of 12h containing sleep (PM groups) or wakefulness (AM groups). MI training should be beneficial compared to no-training for both tasks and age groups, but the impact of sleep on motor memory consolidation should be different. More specifically: (i) for both tasks the level of consolidation after MI training should be greater in young adults compared to older ones; (ii) sleep-dependent consolidation should be observed in both tasks for the young but only in the WBT for the elderly; (iii) a desynchronization of the EEG mu rhythm during MI of the two tasks should be found after learning, but the degree of modulation of mu rhythm could differ between tasks and age groups; (iv) young adults should show higher correlations between sleep spindles and slow wave activity during sleep and motor memory consolidation over sleep, than older adults. Innovation and involved researchers This project notably innovates by the use of a new – ecological but still controlled – sequential WBT. It will provide significant advances in our understanding of the neural underpinnings of motor learning by MI and sleep, and could directly lead to – cost-effective – applications in geriatric rehabilitation. Dr. Saimpont from the University of Lyon (France), and Dr. Hoedlmoser from the University of Salzburg (Austria) will be responsible for this project.

An@tomy2020 aims at developing an innovative educational platform to facilitate learning of functional anatomy. This platform will integrate recent advances in computer graphics, human-computer interaction together with recent insights in educational and cognitive sciences to design and test optimal scenarios for anatomy learning. It will also provide new advances in these respective areas of research. The approach is based on evidences that body movements could improve learning of different knowledge by “augmenting” or “enriching” traces in long-term memory. This “embodied” perspective is particularly relevant for learning of functional anatomy as the knowledge to acquire could be specifically related to the learner’s body in motion. An@tomy2020 will allow connecting learner’s body to anatomical knowledge by tackling technical challenges in relation to pedagogical challenges. Real-time animation of an anatomically realistic model of the user from data acquired with commodity depth sensors and suitable pieces of knowledge extracted from anatomical ontology will be associated with interaction techniques. These associations will favor the construction of 3D spatial representations of the body in motion and the embodiment of knowledge. Our educational tool will thus boost the learners’ spatial abilities helping them building a better spatial representation of the anatomical structure. Optimal interactive techniques will be evaluated. In parallel, the platform will be experienced with medicine and kinesiology students, in real learning conditions. The project is thus organized along three main scientific axes. The aim of the first axis is to provide scientific approaches and technical solutions to capture and animate an accurate model of the user’s body in real-time. A high quality anatomy transfer is required to generate augmented reality views of the user from a deformed generic model. The second axis is dedicated to interaction techniques for precise and seamless interaction in the mixed environment. The aim is to design optimal interaction techniques based on augmented reality methods. Users’ evaluations will be ran to measure their effects on users’ performances, usage convenience, but also on the way knowledge is acquired and represented in users’ memory. The third axis is related to the educational contents and the metrics used for evaluation of trainee abilities. The aim will be to design and test learning scenarios that will integrate the new tools and allow their adaptations to real needs. This will allow drawing the contours of the integration of this new tool in university courses. The project also includes technical challenges related to the integration of the different tools, results and resources in the platform. Six partners participate to this interdisciplinary project: the coordinator TIMC (Computer-Assisted Medical Intervention team) specializes in Computer Science and Applied Mathematics for Healthcare applications; TIMC will coordinate the project and will be mostly involved in user body modeling. Anatoscope is a start-up specialized in anatomy transfer and real-time animation; the company will contribute to user body modeling and will coordinate platform integration. Gipsa-Lab (speech and cognition dept.) studies the behavioral and cognitive processes underlying communicative interactions. It will evaluate the cognitive processes of embodied learning when using new interactive devices. LIBM will bring its knowledge in the study of cognitive processes involved in anatomy learning. LIBM members will also coordinate platform evaluation. LIG (Engineering Human-Computer Interaction team) has extensive experience in designing, developing and evaluating interaction techniques and will coordinate the tasks related to interaction techniques in augmented reality. LJK (Applied Mathematics and Computer Science laboratory) will coordinate formatting and accessibility of the anatomical knowledge and educational content.

Skeletal muscle is a plastic tissue that regenerates ad integrum after injury thanks to the key role of satellite cells (SC) and their dynamic interactions with their niche (e.g., macrophages and fibro-adipogenic progenitors (FAP)). Skeletal muscle regeneration is improved in females as compared with males and is impaired in the absence of estrogens. Epigenetic regulation including lysine-specific demethylase 1 (LSD1), a modulator of estrogen transcriptional activity in the context of cancer, also affects SC fate during regeneration in males. One cause of sexual dimorphism in skeletal muscle regeneration may be therefore the natural fluctuations of estrogens during the ovarian cycle. So far, animal studies have used supraphysiological and constant estrogen doses in ovarian-hormone depleted females, thereby limiting our understanding on how the natural fluctuations of estrogens affect muscle regeneration. Human studies on muscle regeneration are also conflicting, due to the lack of rigorous control of menstrual cycle (MC) together with the confounding effects of contraceptive use. The ESTROMUS project aims i) at investing the impact of estrogenic activity on skeletal muscle regeneration in both animals and Human, ii) at deciphering the underlying cellular, epigenetic and molecular mechanisms. We will determine for the first time how estrogenic cycling activity influences the regulation of the different cell types composing the SC regenerative niche and how they interact together for a proper skeletal muscle regeneration, which is unprecedented. We also aim to delve into the intricate interplay between estrogen signaling and LSD1 activity in physiological contexts, focusing on SC fate determination and skeletal muscle regeneration. So far, the role of epigenetics on skeletal muscle regeneration has been only described in males. By integrating sex-specific epigenetic and transcriptional response we will uncover distinctions in how male and female muscles respond to injury. This approach has the potential to unveil novel insights into the sexually dimorphic aspect of tissue regeneration. Furthermore, even though 17?-estradiol (E2) is the most biological active form of estrogens, other estrogen ligands (i.e., estriol (E3), estetrol (E4)) may play a role in tissue healing. ESTROMUS should go beyond the role of E2 on muscle regeneration by investigating for the first time the impact of E3 and E4 on skeletal muscle homeostasis. This is of utmost interest since E3 and E4 are currently used for therapeutic purposes (contraception, treatment of menopausal symptoms, hormone therapy for menopause). Finally, thanks to an ongoing clinical trial, we will evaluate whether and to what extent the natural hormonal fluctuations across the MC affect skeletal muscle regeneration in Human. We will combine a rigorous control of MC in healthy young females not taking contraceptives, a standardized model of muscle damage together with a longitudinal follow up of muscle function and structure and circulating hormone levels using gas chromatography-mass spectrometry in males and cycling females. The implementation of highly standardized in vitro, ex vivo and in vivo techniques, with specific mouse models and a human model of muscle injury, puts us in a unique position to address the influence of ovarian cycle on ER signaling in both mouse and human muscle regeneration. This is of utmost interest for improving the management of muscle regeneration in healthy females and then in pathological conditions associated with estrogen deficiency/modulation (e.g., sarcopenia, hormone therapy). The strength and success of the project are based on the complementary expertise of three partners, each with a long-standing and unique experience in evaluation of muscle function in both animals and human and cellular, molecular and epigenetic investigations of skeletal muscle.