A5040154818- Neuroscience and Neuropharmacology Research
- Respiratory viral infections research
- Mitochondrial Function and Pathology
- Genetics and Neurodevelopmental Disorders
- Inhalation and Respiratory Drug Delivery
- SARS-CoV-2 and COVID-19 Research
- Retinal Development and Disorders
- Cellular transport and secretion
- Asthma and respiratory diseases
- Photoreceptor and optogenetics research
- Neuroscience and Neural Engineering
- COVID-19 Clinical Research Studies
- RNA modifications and cancer
- Influenza Virus Research Studies
- Cancer Cells and Metastasis
- Neonatal Respiratory Health Research
- Nitric Oxide and Endothelin Effects
- Advanced Chemical Sensor Technologies
- Neural dynamics and brain function
- Ubiquitin and proteasome pathways
- Protein Kinase Regulation and GTPase Signaling
- Autism Spectrum Disorder Research
- Photochromic and Fluorescence Chemistry
- Respiratory and Cough-Related Research
- Infant Health and Development
Genkyotex (Switzerland)
2016-2024
Exelixis (United States)
2024
University of Geneva
2005-2014
Inserm
2004-2005
Hôpital Robert-Debré
2004-2005
University of Szeged
1995-1997
Mutations of the gene coding for PAK3 (p21-activated kinase 3) are associated with X-linked, nonsyndromic forms mental retardation (MRX) in which only distinctive clinical feature is cognitive deficit. The mechanisms through mutation produces handicap remain unclear, although an involvement that regulate formation or plasticity synaptic networks has been proposed. Here we show, using a transient transfection approach, antisense and small interfering RNA-mediated suppression expression...
Postsynaptic density 95 (PSD-95) is an important regulator of synaptic structure and plasticity. However, its contribution to synapse formation organization remains unclear. Using a combined electron microscopic, genetic, pharmacological approach, we uncover new mechanism through which PSD-95 regulates synaptogenesis. We find that overexpression affected spine morphology but also promoted the multiinnervated spines (MISs) contacted by up seven presynaptic terminals. The multiple contacts was...
The p21-activated kinase 3 (PAK3) is one of the recently identified genes for which mutations lead to nonsyndromic mental retardation. PAK3 implicated in dendritic spine morphogenesis and a key regulator synaptic functions. However, underlying roles these processes remain poorly understood. We report here that three R419X, A365E, R67C, responsible retardation have different effects on biological functions PAK3. R419X A365E completely abrogate activity. R67C mutation drastically decreases...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic with unprecedented economic and societal impact. Currently, several vaccines are available multitudes of antiviral treatments have been proposed tested. Although many the show clinical efficacy, they not equally accessible worldwide. Additionally, due to continuous emergence new variants generally short duration immunity, development effective remains utmost importance. Since SARS-CoV-2,...
This work evaluated a non-animal toolbox to be used within next-generation risk assessment (NGRA) framework assess chemical-induced lung effects using human upper and lower respiratory tract models, namely MucilAir™-HF EpiAlveolar™ systems, respectively. A 12-day substance repeated exposure scheme was established explore potential through analysis of bioactivity readouts from the tissue integrity functionality, cytokine/chemokine secretion, transcriptomics. Eleven benchmark chemicals were...
Lower respiratory infections, mostly caused by viral or bacterial pathogens, remain a leading global cause of mortality. The differences between animal models and humans contribute to inefficiencies in drug development, highlighting the need for more relevant predictive, non-animal models. In this context, AlveolAir™, fully primary vitro 3D human alveolar model, was characterized demonstrated sustained presence type I (ATI) II (ATII) cells. This model exhibited functional barrier over 30-day...
The biological mechanisms underlying the mental retardation associated with mutation of ARHGEF6 gene, a Rac1/Cdc42 exchange factor, are still unknown, although defects in plasticity synaptic networks have been postulated. We cloned rat gene and investigated, using transfection approach, its involvement spine morphogenesis relationship to p21-activated kinase 3 (PAK3). found that expression tagged hippocampal slice cultures shows punctate staining dendritic spines colocalizes PSD95....
Several gene mutations linked to intellectual disability in humans code for synaptic molecules implicated small GTPase signaling. This is the case of Rac/Cdc42 effector p21-activated kinase 3 (PAK3). The mechanisms responsible defects and consequences mutation on development wiring brain networks remain unknown. Here we show that expression PAK3 mutants, suppression PAK3, or inhibition function rat hippocampal slice cultures interfere with activity-mediated spine dynamics. Inhibition...
Fragile X syndrome (FXS) is characterized by intellectual disability and autistic traits, results from the silencing of FMR1 gene coding for a protein implicated in regulation synthesis at synapses. The lack functional mental retardation has been proposed to result an excessive signaling synaptic metabotropic glutamate receptors, leading alterations synapse maturation plasticity. It remains, however, unclear how mechanisms activity-dependent spine dynamics are affected Fmr knockout (Fmr1-KO)...
The use of fixed dose-combinations antivirals with different mechanisms action has proven key in the successful treatment infections HIV and HCV. For SARS-CoV-2 possible future epi-/pandemic coronaviruses, it will be important to explore efficacy combinations drugs, particular avoid resistance development, such as patients immunodeficiencies. This work explores effect a combination 3 broad-spectrum antiviral nucleosides on replication coronaviruses. To that end, we made primary human airway...
Respiratory abnormalities have been described in MASH-1 (mammalian achaete-scute homologous gene) and c-RET (“rearranged during transfection”) mutant newborn mice. However, the neural mechanisms underlying these not studied. We tested hypothesis that mutation may impair expression brain stem neurons involved control of breathing. To do this, we analyzed respiratory phenotype +/+ wild-type, +/− heterozygous, −/− knock-out mice first 2 h life. In newborns, gene was absent noradrenergic nuclei...
Abstract PAK1 and PAK3 belong to a family of protein kinases that are effectors small Rho GTPases. In humans, mutations have been associated with mental retardation result in vitro studies defects spine morphogenesis. The functional specificities remain, however, unclear. Here, we investigated using loss gain function experiments how affect morphology hippocampal slice cultures. We find while knockdown is an increase thin, elongated, immature‐type spines, downregulation does not alter...
The use of fixed dose-combinations antivirals with different mechanisms action has proven a key in the successful treatment infections HIV and HCV. For SARS-CoV-2 possible future epi-/pandemic coronaviruses, it will be important to explore efficacy combinations drugs, particular avoid resistance development, such as patients immunodeficiencies. As first effort, we studied antiviral potency antivirals. To that end, made primary human airway epithelial cell (HAEC) cultures grown at air-liquid...