Children's Books as a Tool for Raising Young Readers' Awareness of Dyslexia.

French law requires children with disabilities to receive schooling, wherever possible in ordinary schools. To achieve this goal, schools must create a truly inclusive environment that meets every child's specific needs. Ensuring other students accept peers with disabilities is an essential part of providing an inclusive environment.

Post-translational modifications in prion diseases.

More than 650 reversible and irreversible post-translational modifications (PTMs) of proteins have been listed so far. Canonical PTMs of proteins consist of the covalent addition of functional or chemical groups on target backbone amino-acids or the cleavage of the protein itself, giving rise to modified proteins with specific properties in terms of stability, solubility, cell distribution, activity, or interactions with other biomolecules. PTMs of protein contribute to cell homeostatic processes, enabling basal cell functions, allowing the cell to respond and adapt to variations of its environment, and globally maintaining the constancy of the (the body's inner environment) to sustain human health.

Telepsychology in Europe since COVID-19: How to Foster Social Telepresence?

All over the world, measures were taken to prevent the spread of COVID-19. Social distancing not only had a strong influence on mental health, but also on the organization of care systems. It changed existing practices, as we had to rapidly move from face-to-face contact to remote contact with patients.

Titanium dioxide and carbon black nanoparticles disrupt neuronal homeostasis via excessive activation of cellular prion protein signaling.

Background: Epidemiological emerging evidence shows that human exposure to some nanosized materials present in the environment would contribute to the onset and/or progression of Alzheimer's disease (AD). The cellular and molecular mechanisms whereby nanoparticles would exert some adverse effects towards neurons and take part in AD pathology are nevertheless unknown.

Results: Here, we provide the prime evidence that titanium dioxide (TiO) and carbon black (CB) nanoparticles (NPs) bind the cellular form of the prion protein (PrP), a plasma membrane protein well known for its implication in prion diseases and prion-like diseases, such as AD.

Family Support for (Increasingly) Older Adults with Down Syndrome: Factors Affecting Siblings' Involvement.

Background: Life expectancy for people with Down syndrome is increasing, but older adults with Down syndrome are at greater risk of developing certain pathologies associated with ageing. When ageing parents can no longer look after their child with Down syndrome, their other children are often expected to shoulder this responsibility.

Method: We asked 120 adult siblings of a person with Down syndrome to complete a questionnaire on their current and anticipated relationships.

Loss of prion protein control of glucose metabolism promotes neurodegeneration in model of prion diseases.

Corruption of cellular prion protein (PrPC) function(s) at the plasma membrane of neurons is at the root of prion diseases, such as Creutzfeldt-Jakob disease and its variant in humans, and Bovine Spongiform Encephalopathies, better known as mad cow disease, in cattle. The roles exerted by PrPC, however, remain poorly elucidated. With the perspective to grasp the molecular pathways of neurodegeneration occurring in prion diseases, and to identify therapeutic targets, achieving a better understanding of PrPC roles is a priority.

The Cellular Prion Protein-ROCK Connection: Contribution to Neuronal Homeostasis and Neurodegenerative Diseases.

Amyloid-based neurodegenerative diseases such as prion, Alzheimer's, and Parkinson's diseases have distinct etiologies and clinical manifestations, but they share common pathological events. These diseases are caused by abnormally folded proteins (pathogenic prions PrP in prion diseases, β-amyloids/Aβ and Tau in Alzheimer's disease, α-synuclein in Parkinson's disease) that display β-sheet-enriched structures, propagate and accumulate in the nervous central system, and trigger neuronal death. In prion diseases, PrP-induced corruption of the physiological functions exerted by normal cellular prion proteins (PrP) present at the cell surface of neurons is at the root of neuronal death.

Production of seedable Amyloid-β peptides in model of prion diseases upon PrP-induced PDK1 overactivation.

The presence of amyloid beta (Aβ) plaques in the brain of some individuals with Creutzfeldt-Jakob or Gertsmann-Straussler-Scheinker diseases suggests that pathogenic prions (PrP) would have stimulated the production and deposition of Aβ peptides. We here show in prion-infected neurons and mice that deregulation of the PDK1-TACE α-secretase pathway reduces the Amyloid Precursor Protein (APP) α-cleavage in favor of APP β-processing, leading to Aβ40/42 accumulation. Aβ predominates as monomers, but is also found as trimers and tetramers.

Multifaceted Regulations of the Serotonin Transporter: Impact on Antidepressant Response.

Serotonin transporter, SERT ( for solute carrier family 6, member A4), is a twelve transmembrane domain (TMDs) protein that assumes the uptake of serotonin (5-HT) through dissipation of the Na gradient established by the electrogenic pump Na/K ATPase. Abnormalities in 5-HT level and signaling have been associated with various disorders of the central nervous system (CNS) such as depression, obsessive-compulsive disorder, anxiety disorders, and autism spectrum disorder. Since the 50s, SERT has raised a lot of interest as being the target of a class of antidepressants, the Serotonin Selective Reuptake Inhibitors (SSRIs), used in clinics to combat depressive states.

Serotonin in stem cell based-dental repair and bone formation: A review.

Genetic and pharmacological studies provided evidence that serotonin (5-HT) is an important signaling molecule for the development and the maintenance of mineralized tissues. However, how 5-HT takes part to the homeostasis of teeth and bone remains elusive. In the dental field, a major breakthrough comes from the identification of 5-HT but also dopamine (DA) as "damage" signals necessary for stem cell-based tooth repair.

Protective role of cellular prion protein against TNFα-mediated inflammation through TACE α-secretase.

Although cellular prion protein PrP is well known for its implication in Transmissible Spongiform Encephalopathies, its functions remain elusive. Combining in vitro and in vivo approaches, we here show that PrP displays the intrinsic capacity to protect neuronal cells from a pro-inflammatory TNFα noxious insult. Mechanistically, PrP coupling to the NADPH oxidase-TACE α-secretase signaling pathway promotes TACE-mediated cleavage of transmembrane TNFα receptors (TNFRs) and the release of soluble TNFR, which limits the sensitivity of recipient cells to TNFα.

Alcohol exposure promotes DNA methyltransferase DNMT3A upregulation through reactive oxygen species-dependent mechanisms.

Abundant evidence has accumulated showing that fetal alcohol exposure broadly modifies DNA methylation profiles in the brain. DNA methyltransferases (DNMTs), the enzymes responsible for DNA methylation, are likely implicated in this process. However, their regulation by ethanol exposure has been poorly addressed.

Cerebellar compartmentation of prion pathogenesis.

In prion diseases, the brain lesion profile is influenced by the prion "strain" properties, the invasion route to the brain, and still unknown host cell-specific parameters. To gain insight into those endogenous factors, we analyzed the histopathological alterations induced by distinct prion strains in the mouse cerebellum. We show that 22L and ME7 scrapie prion proteins (PrP , PrP ), but not bovine spongiform encephalopathy PrP , accumulate in a reproducible parasagittal banding pattern in the cerebellar cortex of infected mice.

Prion Protein Deficiency Causes Diverse Proteome Shifts in Cell Models That Escape Detection in Brain Tissue.

A popular method for studying the function of a given protein is to generate and characterize a suitable model deficient for its expression. For the prion protein (PrP), best known for its role in several invariably fatal neurodegenerative diseases, a natural choice, therefore, would be to undertake such studies with brain samples. We recently documented the surprising observation that PrP deficiency caused a loss or enhancement of NCAM1 polysialylation, dependent on the cell model used.

Double-Edge Sword of Sustained ROCK Activation in Prion Diseases through Neuritogenesis Defects and Prion Accumulation.

In prion diseases, synapse dysfunction, axon retraction and loss of neuronal polarity precede neuronal death. The mechanisms driving such polarization defects, however, remain unclear. Here, we examined the contribution of RhoA-associated coiled-coil containing kinases (ROCK), key players in neuritogenesis, to prion diseases.

Essential Roles of Dopamine and Serotonin in Tooth Repair: Functional Interplay Between Odontogenic Stem Cells and Platelets.

Characterizing stem cell intrinsic functions is an ongoing challenge for cell therapies. Here, we report that two independent A4 and H8 stem cell lines isolated from mouse molar pulp display the overall functions of bioaminergic cells. Both clones produce neurotrophins and synthesize, catabolize, store, and transport serotonin (5-hydroxytryptamine [5-HT]) and dopamine (DA).

A PrP(C)-caveolin-Lyn complex negatively controls neuronal GSK3β and serotonin 1B receptor.

The cellular prion protein, PrP(C), is a glycosylphosphatidylinositol-anchored protein, abundant in lipid rafts and highly expressed in the brain. While PrP(C) is much studied for its involvement under its abnormal PrP(Sc) isoform in Transmissible Spongiform Encephalopathies, its physiological role remains unclear. Here, we report that GSK3β, a multifunctional kinase whose inhibition is neuroprotective, is a downstream target of PrP(C) signalling in serotonergic neuronal cells.

Synapto-protective drugs evaluation in reconstructed neuronal network.

Chronic neurodegenerative syndromes such as Alzheimer's and Parkinson's diseases, or acute syndromes such as ischemic stroke or traumatic brain injuries are characterized by early synaptic collapse which precedes axonal and neuronal cell body degeneration and promotes early cognitive impairment in patients. Until now, neuroprotective strategies have failed to impede the progression of neurodegenerative syndromes. Drugs preventing the loss of cell body do not prevent the cognitive decline, probably because they lack synapto-protective effects.

PDK1 decreases TACE-mediated α-secretase activity and promotes disease progression in prion and Alzheimer's diseases.

α-secretase-mediated cleavage of amyloid precursor protein (APP) precludes formation of neurotoxic amyloid-β (Aβ) peptides, and α-cleavage of cellular prion protein (PrP(C)) prevents its conversion into misfolded, pathogenic prions (PrP(Sc)). The mechanisms leading to decreased α-secretase activity in Alzheimer's and prion disease remain unclear. Here, we find that tumor necrosis factor-α-converting enzyme (TACE)-mediated α-secretase activity is impaired at the surface of neurons infected with PrP(Sc) or isolated from APP-transgenic mice with amyloid pathology.

Prolongation of prion disease-associated symptomatic phase relates to CD3+ T cell recruitment into the CNS in murine scrapie-infected mice.

Prion diseases are caused by the transconformation of the host cellular prion protein PrP(c) into an infectious neurotoxic isoform called PrP(Sc). While vaccine-induced PrP-specific CD4(+) T cells and antibodies partially protect scrapie-infected mice from disease, the potential autoreactivity of CD8(+) cytotoxic T lymphocytes (CTLs) received little attention. Beneficial or pathogenic influence of PrP(c)-specific CTL was evaluated by stimulating a CD8(+) T-cell-only response against PrP in scrapie-infected C57BL/6 mice.