Publications by authors named "Denis Mottet"

In the past few years, the double PHD fingers 3 (DPF3) protein isoforms (DPF3b and DPF3a) have been identified as new amyloidogenic intrinsically disordered proteins (IDPs). Although such discovery is coherent and promising in light of their involvement in proteinopathies, their amyloidogenic pathway remains largely unexplored. As environmental variations in pH and ionic strength are relevant to DPF3 pathophysiological landscape, we therefore enquired the effect of these physicochemical parameters on the protein structural and prone-to-aggregation properties, by focusing on the more disordered DPF3a isoform.

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Background: Complex regional pain syndrome (CRPS) is a chronic pain condition characterized by peripheral, central sensory and motor dysfunction. Implicit motor imagery is known to be impaired in CRPS patients, but evidence for explicit motor imagery is still lacking. Using a self-rated questionnaire, this study aims to compare explicit motor imagery abilities between individuals with CRPS, with chronic limb pain (CLP), and healthy controls, and to also examine differences between affected and unaffected limbs.

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Background: Variability in motor recovery after stroke represents a major challenge in its understanding and management. While functional MRI has been used to unravel interactions between stroke motor function and clinical outcome, fMRI alone cannot clarify any relation between brain activation and movement characteristics.

Objectives: We aimed to identify fMRI and kinematic coupling approaches and to evaluate their potential contribution to the understanding of motor function post-stroke.

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Importance: Historical restrictions on children with inherited cardiac arrhythmia or cardiomyopathy have been implemented to mitigate the potential risk of sudden death, but these limitations can be detrimental to overall health and cardiopulmonary fitness.

Objectives: To evaluate cardiopulmonary fitness and physical activity among children with inherited cardiac disease and identify the factors associated with maximum oxygen uptake (V̇o2max) in this population.

Design, Setting, And Participants: This cross-sectional, multicenter, prospective controlled study was conducted in 7 tertiary care expert centers for inherited cardiac disease in France from February 1, 2021, to June 20, 2023, with a 2-week follow-up.

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BackgroundAfter a stroke, the use of the paretic arm is determined by its capacity (what it can or cannot do). When both arms have capacity to perform a task, the choice of which arm to use must be based on another criterion, probably by comparing the efficiency of each arm. Two numerical models account for this: the capacity model (the paretic arm is chosen in preference) and the efficiency model (the most efficient arm is chosen).

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Tuftelin Interacting Protein 11 (TFIP11) was identified as a critical human spliceosome assembly regulator, interacting with multiple proteins and localising in membrane-less organelles. However, a lack of structural information on TFIP11 limits the rationalisation of its biological role. TFIP11 is predicted as an intrinsically disordered protein (IDP), and more specifically concerning its N-terminal (N-TER) region.

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Background: To assess the feasibility, acceptability, safety, and short-term benefits of a tailored cardiac rehabilitation program for children and adolescents with long QT syndrome (LQTS).

Methods: Eight participants, aged between 6 and 18, with a positive LQTS genotype and impaired cardiorespiratory fitness, were enrolled in a 12-week centre-based cardiac rehabilitation program. The program included supervised exercise training group sessions (aerobic, resistance, and outdoor activities) and patient education workshops.

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Following events such as fatigue or stroke, individuals often move their trunks forward during reaching, leveraging a broader muscle group even when only arm movement would suffice. In previous work, we showed the existence of a "force reserve": a phenomenon where individuals, when challenged with a heavy weight, adjusted their motor coordination to preserve approximately 40% of their shoulder's force. Here, we investigated if such reserve can predict hip, shoulder, and elbow movements and torques resulting from an induced shoulder strength deficit.

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DPF3, along with other subunits, is a well-known component of the BAF chromatin remodeling complex, which plays a key role in regulating chromatin remodeling activity and gene expression. Here, we elucidated a non-canonical localization and role for DPF3. We showed that DPF3 dynamically localizes to the centriolar satellites in interphase and to the centrosome, spindle midzone and bridging fiber area, and midbodies during mitosis.

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Article Synopsis
  • DPF3 protein has two splicing variants, DPF3b and DPF3a, linked to human cancer and neurodegeneration, and both can form amyloid fibrils that exhibit a unique deep-blue autofluorescence.
  • The study explored how changing pH and excitation wavelength affects the autofluorescence of these isoforms, revealing different emission modes (violet, deep-blue, and blue-green) and unique photophysical behaviors for each variant.
  • This research suggests that variations in autofluorescence and the structural differences in fibrillar assemblies of DPF3b and DPF3a are influenced by their amino acid compositions and pH-induced changes in molecular interactions.
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Lipid-based nanocarriers have demonstrated high interest in delivering genetic material, exemplified by the success of Onpattro and COVID-19 vaccines. While PEGylation imparts stealth properties, it hampers cellular uptake and endosomal escape, and may trigger adverse reactions like accelerated blood clearance (ABC) and hypersensitivity reactions (HSR). This work highlights the great potential of amphiphilic poly(N-methyl-N-vinylacetamide) (PNMVA) derivatives as alternatives to lipid-PEG for siRNA delivery.

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Article Synopsis
  • - Spinal muscular atrophy is a genetic neuromuscular disorder linked to mutations in the Survival of Motor Neuron (SMN) protein, essential for maintaining healthy motor neurons.
  • - The nucleolus, a key nuclear structure involved in ribosome production, undergoes structural changes during genotoxic stress, with SMN playing a crucial role in restoring its organization post-DNA repair.
  • - The process involves SMN moving from Cajal bodies to the nucleolus during DNA repair, requiring the cooperation of Coilin and PRMT1 for proper nucleolar function.
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The recent approval of Onpattro® and COVID-19 vaccines has highlighted the value of lipid nanoparticles (LNPs) for the delivery of genetic material. If it is known that PEGylation is crucial to confer stealth properties to LNPs, it is also known that PEGylation is responsible for the decrease of the cellular uptake and endosomal escape and for the production of anti-PEG antibodies inducing accelerated blood clearance (ABC) and hypersensitivity reactions. Today, the development of PEG alternatives is crucial.

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Background: To date, many wrist actimetric variables dedicated to measuring the upper limbs (UL) in post-stroke patients have been developed but very few comparisons have been made between them. The objective of this study was to compare different actimetric variables of the ULs between a stroke and healthy population.

Methods: Accelerometers were worn continuously for a period of 7 days on both wrists of 19 post-stroke hemiparetic patients as well as 11 healthy subjects.

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The objective of this study was to validate PLATES for assessing unipodal balance in the field, for example, to monitor ankle instabilities in athletes or patients. PLATES is a pair of lightweight, connected force platforms that measure only vertical forces. In 14 healthy women, we measured ground reaction forces during Single Leg Balance and Single Leg Landing tests, first under laboratory conditions (with PLATES and with a 6-DOF reference force platform), then during a second test session in the field (with PLATES).

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Double-PHD fingers 3 (DPF3) is a BAF-associated human epigenetic regulator, which is increasingly recognised as a major contributor to various pathological contexts, such as cardiac defects, cancer, and neurodegenerative diseases. Recently, we unveiled that its two isoforms (DPF3b and DPF3a) are amyloidogenic intrinsically disordered proteins. DPF3 isoforms differ from their C-terminal region (C-TERb and C-TERa), containing zinc fingers and disordered domains.

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Double PHD fingers 3 (DPF3) is a zinc finger protein, found in the BAF chromatin remodelling complex, and is involved in the regulation of gene expression. Two DPF3 isoforms have been identified, respectively named DPF3b and DPF3a. Very limited structural information is available for these isoforms, and their specific functionality still remains poorly studied.

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Kinematic analysis of the upper limbs is a good way to assess and monitor recovery in individuals with stroke, but it remains little used in clinical routine due to its low feasibility. The aim of this study is to assess the validity and reliability of the Kinect v2 for the analysis of upper limb reaching kinematics. Twenty-six healthy participants performed seated hand-reaching tasks while holding a dumbbell to induce behaviour similar to that of stroke survivors.

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Humans coordinate biomechanical degrees of freedom to perform tasks at minimum cost. When reaching a target from a seated position, the trunk-arm-forearm coordination moves the hand to the well-defined spatial goal, while typically minimising hand jerk and trunk motion. However, due to fatigue or stroke, people visibly move the trunk more, and it is unclear what cost can account for this.

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The U6 snRNA, the core catalytic component of the spliceosome, is extensively modified post-transcriptionally, with 2'-O-methylation being most common. However, how U6 2'-O-methylation is regulated remains largely unknown. Here we report that TFIP11, the human homolog of the yeast spliceosome disassembly factor Ntr1, localizes to nucleoli and Cajal Bodies and is essential for the 2'-O-methylation of U6.

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Background: After a stroke, 80% of the chronic patients have difficulties to use their paretic upper limb (UL) in activities of daily life (ADL) even after rehabilitation. Virtual reality therapy (VRT) and anodal transcranial direct current stimulation (tDCS) are two innovative methods that have shown independently to positively impact functional recovery of the paretic UL when combined with conventional therapy. The objective of the project will be to evaluate the impact of adding anodal high-definition (HD)-tDCS during an intensive 3-week UL VRT and conventional therapy program on paretic UL function in chronic stroke.

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Double PHD fingers 3 (DPF3) is a human epigenetic factor found in the multiprotein BRG1-associated factor (BAF) chromatin remodeling complex. It has two isoforms: DPF3b and DPF3a, but very little is known about the latter. Despite the lack of structural data, it has been established that DPF3a is involved in various protein-protein interactions and that it is subject to phosphorylation.

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Article Synopsis
  • Senescent cells, previously thought to be in a permanent growth arrest, are now linked to both normal and pathological aging, exhibiting specific biomarkers and gene expression changes due to epigenetic factors.
  • Decreased expression of canonical histone deacetylases (HDACs) was observed during the senescence of dermal fibroblasts, and inhibiting HDACs with SAHA or knocking down HDAC2 or HDAC7 leads to increased senescence markers.
  • In contrast, reintroducing HDAC7 in pre-senescent fibroblasts enhances their growth potential, indicating that HDACs play a crucial role in regulating the senescence process and may have potential therapeutic applications for promoting healthy aging.
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The quality of arm movements typically improves in the sub-acute phase of stroke affecting the upper extremity. Here, we used whole arm kinematic analysis during reaching movements to distinguish whether these improvements are due to true recovery or to compensation. Fifty-three participants with post-acute stroke performed ∼80 reaching movement tests during 4 weeks of training with the ArmeoSpring exoskeleton.

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