Enhancing endurance performance with combined imagined and actual physical practice.

PURPOSE: The perception of effort exerts influence in determining task failure during endurance performance. Training interventions blending physical and cognitive tasks yielded promising results in enhancing performance. Motor imagery can decrease the perception of effort. Whether combining motor imagery and physical training improves endurance remains to be understood, and this was the aim of this study. METHODS: Participants (24 ± 3 year) were assigned to a motor imagery (n = 16) or a control (n = 17) group. Both groups engaged in physical exercises targeting the knee extensors (i.e., wall squat, 12 training sessions, 14-days), with participants from the motor imagery group also performing motor imagery. Each participant visited the laboratory Pre and Post-training, during which we assessed endurance performance through a sustained submaximal isometric knee extension contraction until task failure, at either 20% or 40% of the maximal voluntary contraction peak torque. Perceptions of effort and muscle pain were measured during the exercise. RESULTS: We reported no changes in endurance performance for the control group. Endurance performance in the motor imagery group exhibited significant improvements when the intensity of the sustained isometric exercise closely matched that used in training. These enhancements were less pronounced when considering the higher exercise intensity. No reduction in perception of effort was observed in both groups. There was a noticeable decrease in muscle pain perception within the motor imagery group Post training. CONCLUSION: Combining motor imagery and physical training may offer a promising avenue for enhancing endurance performance and managing pain in various contexts.

Hippocampal and neocortical BRAF mutant non-expansive lesions in focal epilepsies.

OBJECTIVE: Mesial Temporal Lobe Epilepsy-associated Hippocampal Sclerosis (MTLE-HS) is a syndrome associated with various aetiologies. We previously identified CD34-positive extravascular stellate cells (CD34+ cells) possibly related to BRAFV600E oncogenic variant in a subset of MTLE-HS. We aimed to identify the BRAFV600E oncogenic variants and characterise the CD34+ cells. METHODS: We analysed BRAFV600E oncogenic variant by digital droplet Polymerase Chain Reaction in 53 MTLE-HS samples (25 with CD34+ cells) and nine non-expansive neocortical lesions resected during epilepsy surgery (five with CD34+ cells). Ex vivo multi-electrode array recording, immunolabelling, methylation microarray and single nuclei RNAseq were performed on BRAFwildtype MTLE-HS and BRAFV600E mutant non-expansive lesion of hippocampus and/or neocortex. RESULTS: We identified a BRAFV600E oncogenic variant in five MTLE-HS samples with CD34+ cells (19%) and in five neocortical samples with CD34+ cells (100%). Single nuclei RNAseq of resected samples revealed two unique clusters of abnormal cells (including CD34+ cells) associated with senescence and oligodendrocyte development in both hippocampal and neocortical BRAFV600E mutant samples. The co-expression of the oncogene-induced senescence marker p16INK4A and the outer subventricular zone radial glia progenitor marker HOPX in CD34+ cells was confirmed by multiplex immunostaining. Pseudotime analysis showed that abnormal cells share a common lineage from progenitors to myelinating oligodendrocytes. Epilepsy surgery led to seizure freedom in eight of the 10 patients with BRAF mutant lesions. INTERPRETATION: BRAFV600E underlies a subset of MTLE-HS and epileptogenic non-expansive neocortical focal lesions. Detection of the oncogenic variant may help diagnosis and open perspectives for targeted therapies.

Applications of chitosan in the agri-food sector: A review.

Chitosan is a natural and renewable polysaccharide that can form biopolymers. It is derived from the deacetylation of chitin mainly from crustaceans' shells, but also from fungi and insects. Thanks to unique characteristics such as antimicrobial effects, antioxidant properties or film forming capacities, it has triggered an important amount of research in the last decade about possible applications in industrial fields. The main application field of chitosan is the food industry where it can be used for preservation purposes and shelf-life improvement for fresh food products such as fruits or meat. For beverages, it is used for clarification and fining as well as elimination of spoilage flora in beverages like fruit juices or wine. And in agriculture, it can be used as a plant protection product through different mechanisms like the elicitation of plant defences. The mechanisms of action of chitosan on microorganisms are multiple and complex but revolve mostly around the disturbance of microorganisms' membranes and cell walls resulting in the leakage of cell material. The use of chitosan is still minor but is promising in finding environmentally friendly alternatives to synthetic chemicals and plastics. Therefore, its characterization is primordial for the future of sustainable production and preservation processes.

Effects of prolonged vibration to the flexor carpi radialis muscle on intracortical excitability.

Prolonged local vibration (LV) can induce neurophysiological adaptations thought to be related to long-term potentiation or depression. Yet, how changes in intracortical excitability may be involved remains to be further investigated as previous studies reported equivocal results. We therefore investigated the effects of 30 min of LV applied to the right flexor carpi radialis muscle (FCR) on both short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). SICI and ICF were measured through transcranial magnetic stimulation before and immediately after 30 min of FCR LV (vibration condition) or 30 min of rest (control condition). Measurements were performed during a low-intensity contraction (n = 17) or at rest (n = 7). No significant SICI nor ICF modulations were observed, whether measured during isometric contractions or at rest (p = 0.2). Yet, we observed an increase in inter-individual variability for post measurements after LV. In conclusion, while intracortical excitability was not significantly modulated after LV, increased inter-variability observed after LV may suggest the possibility of divergent responses to prolonged LV exposure.

Contribution of the subthalamic nucleus to motor, cognitive and limbic processes: an electrophysiological and stimulation study in monkeys.

Deep brain stimulation of the subthalamic nucleus (STN) has become the gold standard surgical treatment for Parkinson's disease and is being investigated for obsessive compulsive disorders. Even if the role of the STN in the behavior is well documented, its organization and especially its division into several functional territories is still debated. A better characterization of these territories and a better knowledge of the impact of stimulation would address this issue. We aimed to find specific electrophysiological markers of motor, cognitive and limbic functions within the STN and to specifically modulate these components. Two healthy non-human primates (Macaca fascicularis) performed a behavioral task allowing the assessment of motor, cognitive and limbic reward-related behavioral components. During the task, four contacts in the STN allowed recordings and stimulations, using low frequency stimulation (LFS) and high frequency stimulation (HFS). Specific electrophysiological functional markers were found in the STN with beta band activity for the motor component of behavior, theta band activity for the cognitive component, and, gamma and theta activity bands for the limbic component. For both monkeys, dorsolateral HFS and LFS of the STN significantly modulated motor performances, whereas only ventromedial HFS modulated cognitive performances. Our results validated the functional overlap of dorsal motor and ventral cognitive subthalamic territories, and, provide information that tends toward a diffuse limbic territory sensitive to the reward within the STN.

Motor Imagery Training Is Beneficial for Motor Memory of Upper and Lower Limb Tasks in Very Old Adults.

Human aging is associated with a decline in the capacity to memorize recently acquired motor skills. Motor imagery training is a beneficial method to compensate for this deterioration in old adults. It is not yet known whether these beneficial effects are maintained in very old adults (>80 years), who are more affected by the degeneration processes. The aim of this study was to evaluate the effectiveness of a mental training session of motor imagery on the memorization of new motor skills acquired through physical practice in very old adults. Thus, 30 very old adults performed 3 actual trials of a manual dexterity task (session 1) or a sequential footstep task (session 2) as fast as they could before and after a 20 min motor imagery training (mental-training group) or watching a documentary for 20 min (control group). Performance was improved after three actual trials for both tasks and both groups. For the control group, performance decreased in the manual dexterity task after the 20 min break and remained stable in the sequential footstep task. For the mental-training group, performance was maintained in the manual dexterity task after the 20 min motor imagery training and increased in the sequential footstep task. These results extended the benefits of motor imagery training to the very old population, showing that even a short motor imagery training session improved their performance and favored the motor memory process. These results confirmed that motor imagery training is an effective method to complement traditional rehabilitation protocols.

Measuring objective fatigability and autonomic dysfunction in clinical populations: How and why?

Fatigue is a major symptom in many diseases, often among the most common and severe ones and may last for an extremely long period. Chronic fatigue impacts quality of life, reduces the capacity to perform activities of daily living, and has socioeconomical consequences such as impairing return to work. Despite the high prevalence and deleterious consequences of fatigue, little is known about its etiology. Numerous causes have been proposed to explain chronic fatigue. They encompass psychosocial and behavioral aspects (e.g., sleep disorders) and biological (e.g., inflammation), hematological (e.g., anemia) as well as physiological origins. Among the potential causes of chronic fatigue is the role of altered acute fatigue resistance, i.e. an increased fatigability for a given exercise, that is related to physical deconditioning. For instance, we and others have recently evidenced that relationships between chronic fatigue and increased objective fatigability, defined as an abnormal deterioration of functional capacity (maximal force or power), provided objective fatigability is appropriately measured. Indeed, in most studies in the field of chronic diseases, objective fatigability is measured during single-joint, isometric exercises. While those studies are valuable from a fundamental science point of view, they do not allow to test the patients in ecological situations when the purpose is to search for a link with chronic fatigue. As a complementary measure to the evaluation of neuromuscular function (i.e., fatigability), studying the dysfunction of the autonomic nervous system (ANS) is also of great interest in the context of fatigue. The challenge of evaluating objective fatigability and ANS dysfunction appropriately (i.e.,. how?) will be discussed in the first part of the present article. New tools recently developed to measure objective fatigability and muscle function will be presented. In the second part of the paper, we will discuss the interest of measuring objective fatigability and ANS (i.e. why?). Despite the beneficial effects of physical activity in attenuating chronic fatigue have been demonstrated, a better evaluation of fatigue etiology will allow to personalize the training intervention. We believe this is key in order to account for the complex, multifactorial nature of chronic fatigue.

Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma.

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, yet it remains refractory to systemic therapy. Elimination of senescent cells has emerged as a promising new treatment approach against cancer. Here, we investigated the contribution of senescent cells to GBM progression. Senescent cells are identified in patient and mouse GBMs. Partial removal of p16Ink4a-expressing malignant senescent cells, which make up less than 7 % of the tumor, modifies the tumor ecosystem and improves the survival of GBM-bearing female mice. By combining single cell and bulk RNA sequencing, immunohistochemistry and genetic knockdowns, we identify the NRF2 transcription factor as a determinant of the senescent phenotype. Remarkably, our mouse senescent transcriptional signature and underlying mechanisms of senescence are conserved in patient GBMs, in whom higher senescence scores correlate with shorter survival times. These findings suggest that senolytic drug therapy may be a beneficial adjuvant therapy for patients with GBM.

Spatial and ontogenetic variations in sardine feeding conditions in the Bay of Biscay through fatty acid composition.

Food characteristics are amongst the most influential factors determining the fish life history traits as quantitative and qualitative changes in individuals' diet can lead to a decline in the energy allocated to their growth, and hence influence natural populations' characteristics. The size-at-age and weight of European sardines (Sardina pilchardus) in the Bay of Biscay (BoB) have decreased substantially over the last decade, especially for the youngest age classes, and the factors underlying such changes have not yet been identified. We therefore analysed the fatty acid (FA) composition in the neutral (NL) and polar (PL) lipids in samples collected across the BoB to determine whether the diet of sardines changes with their ages. We found that the total FA contents in both lipid fractions varied mainly with the sampling locations and age. Indeed, sardines aged 1 and 2 years living in South BoB had particularly high contents in FA specific to non-diatom phytoplankton, while older sardines living in the Northern part had higher total FA content and more FA specific to copepods. These differences probably resulted from differences in prey availability and to a lesser extend a change in feeding behaviour with age. The strong dependence of younger sardines' diet to phytoplankton in spring suggests that changes in primary production may explain their decline in size-at-age. Finally, NL clearly reflect finest feeding variations in comparison to PL imprinted by diet variations at longer time scale. Future studies should consider separately NL and PL fractions.

Oral Ursodeoxycholic Acid Crosses the Blood Retinal Barrier in Patients with Retinal Detachment and Protects Against Retinal Degeneration in an Ex Vivo Model.

Rhegmatogenous retinal detachment (RD) is a threatening visual condition and a human disease model for retinal degenerations. Despite successful reattachment surgery, vision does not fully recover, due to subretinal fluid accumulation and subsequent photoreceptor cell death, through mechanisms that recapitulate those of retinal degenerative diseases. Hydrophilic bile acids are neuroprotective in animal models, but whether they can be used orally for retinal diseases is unknown. Ursodeoxycholic acid (UDCA) being approved for clinical use (e.g., in cholestasis), we have evaluated the ocular bioavailability of oral UDCA, administered to patients before RD surgery. The level of UDCA in ocular media correlated with the extent of blood retinal barrier disruption, evaluated by the extent of detachment and the albumin concentration in subretinal fluid. UDCA, at levels measured in ocular media, protected photoreceptors from apoptosis and necrosis in rat retinal explants, an ex vivo model of RD. The subretinal fluid from UDCA-treated patients, collected during surgery, significantly protected rat retinal explants from cell death, when compared to subretinal fluid from control patients. Pan-transcriptomic analysis of the retina showed that UDCA upregulated anti-apoptotic, anti-oxidant, and anti-inflammatory genes. Oral UDCA is a potential neuroprotective adjuvant therapy in RD and other retinal degenerative diseases and should be further evaluated in a clinical trial.

Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum.

Brain neurons arise from relatively few progenitors generating an enormous diversity of neuronal types. Nonetheless, a cardinal feature of mammalian brain neurogenesis is thought to be that excitatory and inhibitory neurons derive from separate, spatially segregated progenitors. Whether bi-potential progenitors with an intrinsic capacity to generate both lineages exist and how such a fate decision may be regulated are unknown. Using cerebellar development as a model, we discover that individual progenitors can give rise to both inhibitory and excitatory lineages. Gradations of Notch activity determine the fates of the progenitors and their daughters. Daughters with the highest levels of Notch activity retain the progenitor fate, while intermediate levels of Notch activity generate inhibitory neurons, and daughters with very low levels of Notch signaling adopt the excitatory fate. Therefore, Notch-mediated binary cell fate choice is a mechanism for regulating the ratio of excitatory to inhibitory neurons from common progenitors.