Le stress comme facteur de risque des maladies parodontales

CLERMONT FD-BCIU Odontol. (631132226) / SudocPARIS-BIUM (751062103) / SudocCLERMONT FD-BCIU-Santé (631132104) / SudocSudocFranceF

Mutations in DNAH17, Encoding a Sperm-Specific Axonemal Outer Dynein Arm Heavy Chain, Cause Isolated Male Infertility Due to Asthenozoospermia

International audienceMotile cilia and sperm flagella share an evolutionarily conserved axonemal structure. Their structural and/or functional defects are associated with primary ciliary dyskinesia (PCD), a genetic disease characterized by chronic respiratory-tract infections and in which most males are infertile due to asthenozoospermia. Among the well-characterized axonemal protein complexes, the outer dynein arms (ODAs), through ATPase activity of their heavy chains (HCs), play a major role for cilia and flagella beating. However, the contribution of the different HCs (γ-type: DNAH5 and DNAH8 and β-type: DNAH9, DNAH11, and DNAH17) in ODAs from both organelles is unknown. By analyzing five male individuals who consulted for isolated infertility and displayed a loss of ODAs in their sperm cells but not in their respiratory cells, we identified bi-allelic mutations in DNAH17. The isolated infertility phenotype prompted us to compare the protein composition of ODAs in the sperm and ciliary axonemes from control individuals. We show that DNAH17 and DNAH8, but not DNAH5, DNAH9, or DNAH11, colocalize with α-tubulin along the sperm axoneme, whereas the reverse picture is observed in respiratory cilia, thus explaining the phenotype restricted to sperm cells. We also demonstrate the loss of function associated with DNAH17 mutations in two unrelated individuals by performing immunoblot and immunofluorescence analyses on sperm cells; these analyses indicated the absence of DNAH17 and DNAH8, whereas DNAH2 and DNALI, two inner dynein arm components, were present. Overall, this study demonstrates that mutations in DNAH17 are responsible for isolated male infertility and provides information regarding ODA composition in human spermatozoa

Les mutations de DNAH17 causent une infertilité isolée par asthénospermie par défaut d’une dynéine axonémale spécifique du flagelle des spermatozoïdes

National audienceMotile cilia and sperm flagella share an evolutionarily conserved axonemal structure. Their structural and/or functional defects are associated with primary ciliary dyskinesia (PCD), a genetic disease characterized by chronic respiratory-tract infections and in which most males are infertile due to asthenozoospermia. Among the well-characterized axonemal protein complexes, the outer dynein arms (ODAs), through ATPase activity of their heavy chains (HCs), play a major role for cilia and flagella beating. However, the contribution of the different HCs (gtype: DNAH5 and DNAH8 and btype: DNAH9, DNAH11, and DNAH17) in ODAs from both organelles is unknown. By analyzing five male individuals who consulted for isolated infertility and displayed a loss of ODAs in their sperm cells but not in their respiratory cells, we identified bi-allelic mutations in DNAH17. The isolated infertility phenotype prompted us to compare the protein composition of ODAs in the sperm and ciliary axonemes from control individuals. We show that DNAH17 and DNAH8, but not DNAH5, DNAH9, or DNAH11, colocalize with a-tubulin along the sperm axoneme, whereas the reverse picture is observed in respiratory cilia, thus explaining the phenotype restricted to sperm cells. We also demonstrate the loss of function associated with DNAH17 mutations in two unrelated individuals by performing immunoblot and immunofluorescence analyses on sperm cells; these analyses indicated the absence of DNAH17 and DNAH8, whereas DNAH2 and DNALI, two inner dynein arm components, were present. Overall, this study demonstrates that mutations in DNAH17 are responsible for isolated male infertility and provides information regarding ODA composition in human spermatozoa

Self-reported loss of smell without nasal obstruction to identify COVID-19. The multicenter Coranosmia cohort study

International audienceObjectives: To determine the frequency of SARS-CoV-2 positive samples in a subset of patients consulting for primarily isolated acute (<7 days) loss of smell and to assess the diagnostic accuracy of olfactory/gustatory dysfunction for COVID-19 diagnosis in the overall population tested for COVID-19 in the same period.Methods: Prospective multicentric cohort study in four olfactory ENT units and a screening center for COVID-19.Results: i) Among a subset of 55 patients consulting for primarily recent loss of smell, we found that 51 (92.7%) had a COVID-19 positive test (median viral load of 28.8 cycle threshold). Loss of smell was mostly total (anosmia), rarely associated with nasal obstruction but associated with a taste disorder in 80%. Olfactory dysfunction occurred suddenly, either as first complaint or preceded by mild symptoms occurring a median of 3 days. The majority of patients (72.9%) partially recovered the sense of smell within 15 days. ii) In a population of 1824 patients tested for COVID-19, the positive predictive value and the specificity of loss of smell and/or taste were 78.5% and 90.3% respectively (sensitivity (40.8%), negative predictive value (63.6%)).Conclusions: Self-reported loss of smell had a high predictive positive value to identify COVID-19. Making this sign well known publicly could help to adopt isolation measures and inform potential contacts

TTC12 Loss-of-Function Mutations Cause Primary Ciliary Dyskinesia and Unveil Distinct Dynein Assembly Mechanisms in Motile Cilia Versus Flagella

International audienceCilia and flagella are evolutionarily conserved organelles whose motility relies on the outer and inner dynein arm complexes (ODAs and IDAs). Defects in ODAs and IDAs result in primary ciliary dyskinesia (PCD), a disease characterized by recurrent airway infections and male infertility. PCD mutations in assembly factors have been shown to cause a combined ODA-IDA defect, affecting both cilia and flagella. We identified four loss-of-function mutations in TTC12, which encodes a cytoplasmic protein, in four independent families in which affected individuals displayed a peculiar PCD phenotype characterized by the absence of ODAs and IDAs in sperm flagella, contrasting with the absence of only IDAs in respiratory cilia. Analyses of both primary cells from individuals carrying TTC12 mutations and human differentiated airway cells invalidated for TTC12 by a CRISPR-Cas9 approach revealed an IDA defect restricted to a subset of single-headed IDAs that are different in flagella and cilia, whereas TTC12 depletion in the ciliate Paramecium tetraurelia recapitulated the sperm phenotype. Overall, our study, which identifies TTC12 as a gene involved in PCD, unveils distinct dynein assembly mechanisms in human motile cilia versus flagella

TTC12 loss-of-function mutations cause primary ciliary dyskinesia and unveil distinct dynein assemblymechanisms in motile cilia versus flagella

International audienceCilia and flagella are evolutionarily conserved organelles whose motility relies on the outer and inner dynein arm complexes (ODAs/IDAs). Defects in ODAs/IDAs result in primary ciliary dyskinesia (PCD), a disease characterized by recurrent airway infections and male infertility. To date PCD mutations in assembly factors cause a combined ODA/IDA defect, affecting both cilia and flagella. We identified four loss-of-function mutations in TTC12, which encodes a cytoplasmic protein, in four independent families in which affected individuals displayed a peculiar PCD phenotype characterized by the absence of ODAs and IDAs in sperm flagella, contrasting with the sole absence of IDAs in respiratory cilia. We analysed both primary cells from individuals carrying TTC12 mutations and human differentiated airway cells invalidated for TTC12 by a CRISPR-Cas9 approach, as well as TTC12 depletion in the ciliated model, Paramecium tetraureli. Our results revealed an IDA defect restricted to a subset of single-headed IDAs different in flagella and cilia, while TTC12 depletion in Paramecium tetraurelia recapitulated the sperm phenotype. Overall, our study, which identifies TTC12 as a new gene involved in PCD, unveils distinct dynein assembly mechanisms in human motile cilia versus flagella

TTC12 loss-of-function mutations cause primary ciliary dyskinesia and unveil distinct dynein assemblymechanisms in motile cilia versus flagella

International audienceCilia and flagella are evolutionarily conserved organelles whose motility relies on the outer and inner dynein arm complexes (ODAs/IDAs). Defects in ODAs/IDAs result in primary ciliary dyskinesia (PCD), a disease characterized by recurrent airway infections and male infertility. To date PCD mutations in assembly factors cause a combined ODA/IDA defect, affecting both cilia and flagella. We identified four loss-of-function mutations in TTC12, which encodes a cytoplasmic protein, in four independent families in which affected individuals displayed a peculiar PCD phenotype characterized by the absence of ODAs and IDAs in sperm flagella, contrasting with the sole absence of IDAs in respiratory cilia. We analysed both primary cells from individuals carrying TTC12 mutations and human differentiated airway cells invalidated for TTC12 by a CRISPR-Cas9 approach, as well as TTC12 depletion in the ciliated model, Paramecium tetraureli. Our results revealed an IDA defect restricted to a subset of single-headed IDAs different in flagella and cilia, while TTC12 depletion in Paramecium tetraurelia recapitulated the sperm phenotype. Overall, our study, which identifies TTC12 as a new gene involved in PCD, unveils distinct dynein assembly mechanisms in human motile cilia versus flagella

TTC12 loss-of-function mutations cause primary ciliary dyskinesia and unveil distinct dynein assemblymechanisms in motile cilia versus flagella

International audienceCilia and flagella are evolutionarily conserved organelles whose motility relies on the outer and inner dynein arm complexes (ODAs/IDAs). Defects in ODAs/IDAs result in primary ciliary dyskinesia (PCD), a disease characterized by recurrent airway infections and male infertility. To date PCD mutations in assembly factors cause a combined ODA/IDA defect, affecting both cilia and flagella. We identified four loss-of-function mutations in TTC12, which encodes a cytoplasmic protein, in four independent families in which affected individuals displayed a peculiar PCD phenotype characterized by the absence of ODAs and IDAs in sperm flagella, contrasting with the sole absence of IDAs in respiratory cilia. We analysed both primary cells from individuals carrying TTC12 mutations and human differentiated airway cells invalidated for TTC12 by a CRISPR-Cas9 approach, as well as TTC12 depletion in the ciliated model, Paramecium tetraureli. Our results revealed an IDA defect restricted to a subset of single-headed IDAs different in flagella and cilia, while TTC12 depletion in Paramecium tetraurelia recapitulated the sperm phenotype. Overall, our study, which identifies TTC12 as a new gene involved in PCD, unveils distinct dynein assembly mechanisms in human motile cilia versus flagella

TTC12 loss-of-function mutations cause primary ciliary dyskinesia and unveil distinct dynein assemblymechanisms in motile cilia versus flagella

International audienceCilia and flagella are evolutionarily conserved organelles whose motility relies on the outer and inner dynein arm complexes (ODAs/IDAs). Defects in ODAs/IDAs result in primary ciliary dyskinesia (PCD), a disease characterized by recurrent airway infections and male infertility. To date PCD mutations in assembly factors cause a combined ODA/IDA defect, affecting both cilia and flagella. We identified four loss-of-function mutations in TTC12, which encodes a cytoplasmic protein, in four independent families in which affected individuals displayed a peculiar PCD phenotype characterized by the absence of ODAs and IDAs in sperm flagella, contrasting with the sole absence of IDAs in respiratory cilia. We analysed both primary cells from individuals carrying TTC12 mutations and human differentiated airway cells invalidated for TTC12 by a CRISPR-Cas9 approach, as well as TTC12 depletion in the ciliated model, Paramecium tetraureli. Our results revealed an IDA defect restricted to a subset of single-headed IDAs different in flagella and cilia, while TTC12 depletion in Paramecium tetraurelia recapitulated the sperm phenotype. Overall, our study, which identifies TTC12 as a new gene involved in PCD, unveils distinct dynein assembly mechanisms in human motile cilia versus flagella

TTC12 loss-of-function mutations cause primary ciliary dyskinesia and unveil distinct dynein assemblymechanisms in motile cilia versus flagella

International audienceCilia and flagella are evolutionarily conserved organelles whose motility relies on the outer and inner dynein arm complexes (ODAs/IDAs). Defects in ODAs/IDAs result in primary ciliary dyskinesia (PCD), a disease characterized by recurrent airway infections and male infertility. To date PCD mutations in assembly factors cause a combined ODA/IDA defect, affecting both cilia and flagella. We identified four loss-of-function mutations in TTC12, which encodes a cytoplasmic protein, in four independent families in which affected individuals displayed a peculiar PCD phenotype characterized by the absence of ODAs and IDAs in sperm flagella, contrasting with the sole absence of IDAs in respiratory cilia. We analysed both primary cells from individuals carrying TTC12 mutations and human differentiated airway cells invalidated for TTC12 by a CRISPR-Cas9 approach, as well as TTC12 depletion in the ciliated model, Paramecium tetraureli. Our results revealed an IDA defect restricted to a subset of single-headed IDAs different in flagella and cilia, while TTC12 depletion in Paramecium tetraurelia recapitulated the sperm phenotype. Overall, our study, which identifies TTC12 as a new gene involved in PCD, unveils distinct dynein assembly mechanisms in human motile cilia versus flagella