A new index for characterizing micro-bead motion in a flow induced by ciliary beating: Part I, experimental analysis.

Mucociliary clearance is one of the major lines of defense of the respiratory system. The mucus layer coating the pulmonary airways is moved along and out of the lung by the activity of motile cilia, thus expelling the particles trapped in it. Here we compare ex vivo measurements of a Newtonian flow induced by cilia beating (using micro-beads as tracers) and a mathematical model of this fluid flow, presented in greater detail in a second companion article. Samples of nasal epithelial cells placed in water are recorded by high-speed video-microscopy and ciliary beat pattern is inferred. Automatic tracking of micro-beads, used as markers of the flow generated by cilia motion, enables us also to assess the velocity profile as a function of the distance above the cilia. This profile is shown to be essentially parabolic. The obtained experimental data are used to feed a 2D mathematical and numerical model of the coupling between cilia, fluid, and micro-bead motion. From the model and the experimental measurements, the shear stress exerted by the cilia is deduced. Finally, this shear stress, which can easily be measured in the clinical setting, is proposed as a new index for characterizing the efficiency of ciliary beating

« Paralysie récurrentielle unilatérale après thyroïdectomie : savoir rechercher un syndrome d’hyperventilation »

International audienceLa paralysie unilatérale du nerf récurrent peut être responsable d’une dysphonie et de troubles de la déglutition. La physiopathologie de l’apparition d’une dyspnée induite par une paralysie récurrentielle unilatérale n’est pas complètement élucidée. Notre hypothèse est que la fuite d’air au niveau glottique pourrait être responsable du développement d’un syndrome d’hyperventilation (SHV).ObjectifL’objectif de cette étude était de déterminer, chez les patients atteints de paralysie récurrentielle unilatérale, si la dyspnée pouvait être associée au SHV.Matériel et méthodesSur une période de 12 mois, tous les patients atteints de paralysie récurrentielle unilatérale permanente (> 6 mois) après thyroïdectomie se plaignant de l’apparition d’une dyspnée inexpliquée ont été explorés. Les tests suivants ont été réalisés : score de Nijmegen, test d’hyperventilation provoquée, gazométrie artérielle, épreuves fonctionnelles respiratoires et tests cardiaques. Le diagnostic de SHV a été posé si au moins deux critères étaient présents parmi les suivants : score de Nijmegen > 23 ; reproduction d’au moins 2 symptômes habituels lors du test d’hyperventilation ; pression télé-expiratoire en CO2 (PetCO2) < 30 mmHg ou < 90 % de la PetCO2 initiale après une période de récupération de 5 min à la suite d’une hyperventilation volontaire de 3 min.RésultatsDix patients sur 366 opérés d’une thyroïdectomie pour une maladie bénigne présentaient une paralysie récurrentielle unilatérale permanente et une dyspnée. Parmi les 10 patients inclus, chez 8 le diagnostic de SHV a été retenu lors du test d’hyperventilation provoquée sans dysfonctionnement cardiaque/pulmonaire.ConclusionEn résumé, cette étude est en faveur de l’implication du SHV dans la dyspnée associée à la paralysie récurrentielle unilatérale

Deep phenotyping, including quantitative ciliary beating parameters, and extensive genotyping in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder resulting in abnormal ciliary motility/structure, extremely heterogeneous at genetic and ultrastructural levels. We aimed, in light of extensive genotyping, to identify specific and quantitative ciliary beating anomalies, according to the ultrastructural phenotype. We prospectively included 75 patients with PCD exhibiting the main five ultrastructural phenotypes (n=15/group), screened all corresponding PCD genes and measured quantitative beating parameters by high-speed video-microscopy (HSV). Sixty-eight (91%) patients carried biallelic mutations. Combined outer/inner dynein arms (ODA/IDA) defect induces total ciliary immotility, regardless of the gene involved. ODA defect induces a residual beating with dramatically low ciliary beat frequency (CBF) related to increased recovery stroke and pause durations, especially in case of DNAI1 mutations. IDA defect with microtubular disorganisation induces a low percentage of beating cilia with decreased beating angle and, in case of CCDC39 mutations, a relatively conserved mean CBF with a high maximal CBF. Central complex defect induces nearly normal beating parameters, regardless of the gene involved, and a gyrating motion in a minority of ciliated edges, especially in case of RSPH1 mutations. PCD with normal ultrastructure exhibits heterogeneous HSV values, but mostly an increased CBF with an extremely high maximal CBF. Quantitative HSV analysis in PCD objectives beating anomalies associated with specific ciliary ultrastructures and genotypes. It represents a promising approach to guide the molecular analyses towards the best candidate gene(s) to be analysed or to assess the pathogenicity of the numerous sequence variants identified by next-generation-sequencing

High Ge content Si / SiGe heterostructures for microelectronics and optoelectronics purposes

International audienceSiGe virtual substrates grown by RP-CVD onto Si(001) substrates are characterized by a macroscopic degree of strain relaxation R = 97.2 ± 1.2%, threading dislocations densities as low as 4×105 cm -2 and rather smooth surfaces (rms roughness: 2 - 5 nm). Such virtual substrates have been used as templates for the formation of SiGe-On-Insulator structures (on which we have studied the specifics of Si and SiGe re-epitaxy). We have also grown Ge thick layers directly onto Si(001). Tensile-strained (R = 107%), smooth (rms ∼ 1 nm) Ge layers with a low threading dislocation density (6×106 cm-2) are obtained that are characterized by high absorption coefficients: A = 10000 cm-1 @ 1.3μm and 4500 cm-1 @ 1.55μm. Finally, we have obtained dense, narrowly size-distributed Ge islands that, when integrated into {Ge quantum dots / Si spacer} stacks, emit light at 1520 nm (PL @ 10K) and are characterized by A ∼ 70 cm-1 in-between 1.2 and 1.7 μm

Mutations in DNAJB13, Encoding an HSP40 Family Member, Cause Primary Ciliary Dyskinesia and Male Infertility.

Primary ciliary dyskinesia (PCD) is an autosomal-recessive disease due to functional or ultra-structural defects of motile cilia. Affected individuals display recurrent respiratory-tract infections; most males are infertile as a result of sperm flagellar dysfunction. The great majority of the PCD-associated genes identified so far encode either components of dynein arms (DAs), which are multiprotein-ATPase complexes essential for ciliary motility, or proteins involved in DA assembly. To identify the molecular basis of a PCD phenotype characterized by central complex (CC) defects but normal DA structure, a phenotype found in ∼15% of cases, we performed whole-exome sequencing in a male individual with PCD and unexplained CC defects. This analysis, combined with whole-genome SNP genotyping, identified a homozygous mutation in DNAJB13 (c.833T&gt;G), a gene encoding a HSP40 co-chaperone whose ortholog in the flagellated alga Chlamydomonas localizes to the radial spokes. In vitro studies showed that this missense substitution (p.Met278Arg), which involves a highly conserved residue of several HSP40 family members, leads to protein instability and triggers proteasomal degradation, a result confirmed by the absence of endogenous DNAJB13 in cilia and sperm from this individual. Subsequent DNAJB13 analyses identified another homozygous mutation in a second family; the study of DNAJB13 transcripts obtained from airway cells showed that this mutation (c.68+1G&gt;C) results in a splicing defect consistent with a loss-of-function mutation. Overall, this study, which establishes mutations in DNAJB13 as a cause of PCD, unveils the key role played by DNAJB13 in the proper formation and function of ciliary and flagellar axonemes in humans