Bioenergetic metabolism is a key regulator of cellular function and signaling, but how it can ins... more Bioenergetic metabolism is a key regulator of cellular function and signaling, but how it can instruct the behavior of cells and their fate during embryonic development remains largely unknown. Here, we investigated the role of glucose metabolism in the development of avian trunk neural crest cells (NCCs), a migratory stem cell population of the vertebrate embryo. We uncovered that trunk NCCs display glucose oxidation as a prominent metabolic phenotype, in contrast to what is seen for cranial NCCs, which instead rely on aerobic glycolysis. In addition, only one pathway downstream of glucose uptake is not sufficient for trunk NCC development. Indeed, glycolysis, mitochondrial respiration and the pentose phosphate pathway are all mobilized and integrated for the coordinated execution of diverse cellular programs, epithelial-to-mesenchymal transition, adhesion, locomotion, proliferation and differentiation, through regulation of specific gene expression. In the absence of glucose, the ...
Les voies aeriennes superieures se caracterisent par une succession de singularites anatomiques e... more Les voies aeriennes superieures se caracterisent par une succession de singularites anatomiques et fonctionnelles (naso/oro/hypopharynx) dont le role specifique est de plus en plus mis en evidence chez les patients apneiques et/ou ronfleurs. Par ailleurs, le debit inspire est fortement altere dans les hypopnees obstructives severes et se presente le plus souvent sous forme de plateau a des valeurs de debit tres diminuees par rapport a celles d'inspirations normales. Le but de la these est premierement la prise en compte des singularites pharyngees par un modele a plusieurs elements compliants individualises, dont un element d'aval controle en pression et un (ou plusieurs) element(s) libre(s) d'amont. Les equations de conservation, differentiees par rapport a la pression de controle, aboutissent a un systeme d'equations qui permet de mettre en evidence, sur les variations de la section d'amont et le debit, le role fondamental des indexes de vitesse associes a la distensibilite, s#1 et s#2 (ou leurs valeurs corrigees en fluide visqueux) respectivement definis pour l'element libre d'amont et l'element controle d'aval dans le modele a deux elements. La condition s#1 = 1 et s#2 = 1 correspond a une condition critique alors que la condition s#1 = 1 et s#2 = 1 correspond au point singulier. Cette derniere condition s'avere jouer un role fondamental dans la generation du plateau de debit qui correspond en fait a une succession de maximum et de minimum de debits rapproches avec passages multiples par le point singulier, dependant du nombre d'elements libres. Le modele a ete valide a partir des resultats obtenus chez l'homme (debit et aire pharyngee mesuree par reflexion acoustique) dans les conditions d'inspiration normale et d'hypopnees obstructives severes. Le modele a deux elements lors d'inspiration orale comme le modele a trois elements propose pour l'inspiration nasale permettent de reproduire, dans des gammes de valeurs physiopathologiques, les limitations de debit en plateau et les variations d'aire pharyngee. Le present modele constitue un outil potentiel pour optimiser les moyens therapeutiques utilises pour reduire les hypopnees obstructives : traitement par pression nasale positive, chirurgie et/ou medicaments.
In this work, a sleep apnea diagnosis system based on Hidden Markov Models (HMMs) is presented. C... more In this work, a sleep apnea diagnosis system based on Hidden Markov Models (HMMs) is presented. Conventional and new simulated annealing based methods for the training of HMMs are incorporated. The inference method of this system translates parameter values into ...
We studied eight heavy snorers with upper airway resistance syndrome to investigate potential eff... more We studied eight heavy snorers with upper airway resistance syndrome to investigate potential effects of sleep on expiratory airway and lung resistance, intrinsic positive end-expiratory pressure, hyperinflation, and elastic inspiratory work of breathing (WOB). Wakefulness and nonrapid-eye-movement sleep with high-and with low-resistance inspiratory effort (H-RIE and L-RIE, respectively) were compared. No differences in breathing pattern were seen across the three conditions. In contrast, we found increases in expiratory airway and lung resistance during H-RIE compared with L-RIE and wakefulness (56 Ϯ 24, 16 Ϯ 4, and 11 Ϯ 4 cmH 2 O•l Ϫ1 • s, respectively), with attendant increases in intrinsic positive end-expiratory pressure (5.4 Ϯ 1.8, 1.4 Ϯ 0.5, and 1.3 Ϯ 1.3 cmH 2 O, respectively) and elastic WOB (6.1 Ϯ 2.2, 3.7 Ϯ 1.2, and 3.4 Ϯ 0.7 J/min, respectively). The increase in WOB during H-RIE is partly caused by the effects of dynamic pulmonary hyperinflation produced by the increased expiratory resistance. Contrary to the Starling model, a multiple-element compliance model that takes into account the heterogeneity of the pharynx may explain flow limitation during expiration.
Le pilote de chasse subit frequemment des accelerations +Gz (accelerations dont les forces d'... more Le pilote de chasse subit frequemment des accelerations +Gz (accelerations dont les forces d'inertie sont dirigees vers les membres inferieurs). Ces accelerations pourraient induire une obstruction des voies aeriennes superieures (VAS) par un mecanoreflexe d'origine pulmonaire, par un deplacement du volume sanguin lingual et pharynge ou par effet mecanique direct de la variation de gravite. Pour definir la contribution de ces trois mecanismes, nous avons evalue, respectivement par plethysmographie a variation d'inductance et par une methode de reflexion acoustique, le volume pulmonaire en fin d'expiration (EEV) et la surface des VAS chez 6 sujets sains en position assise et couchee au cours de periodes de gravite de 0, 1 et 2 +Gz observees lors de vols paraboliques. Lorsque la gravite augmente de 0 a 2 +Gz, on observe, en position assise, une augmentation de la surface des regions palato-pharyngee et retrobasilinguale (+30% et +20% (p < 0.05), respectivement) et d...
We measured upper airway caliber and lung volumes in six normal subjects in the sitting and supin... more We measured upper airway caliber and lung volumes in six normal subjects in the sitting and supine positions during 20-s periods in normogravity, hypergravity [1.8 + head-to-foot acceleration (Gz)], and microgravity (∼0 Gz) induced by parabolic flights. Airway caliber and lung volumes were inferred by the acoustic reflection method and inductance plethysmography, respectively. In subjects in the sitting position, an increase in gravity from 0 to 1.8 +Gz was associated with increases in the calibers of the retrobasitongue and palatopharyngeal regions (+20 and +30%, respectively) and with a concomitant 0.5-liter increase in end-expiratory lung volume (functional residual capacity, FRC). In subjects in the supine position, no changes in the areas of these regions were observed, despite significant decreases in FRC from microgravity to normogravity (−0.6 liter) and from microgravity to hypergravity (−0.5 liter). Laryngeal narrowing also occurred in both positions (about −15%) when gravi...
This report concerns the inference of geometric and mechanical airway characteristics based on in... more This report concerns the inference of geometric and mechanical airway characteristics based on information derived from a single transient planar wave recorded at the airway opening. We describe a new method to simultaneously measure upper airway area and respiratory input impedance by performing dual analysis of a single pressure wave. The algorithms required to reconstruct airway dimensions and mechanical characteristics were developed, implemented, and tested with reference to known physical models. Our method appears suitable to estimate, even under severe intensive care unit conditions, the respiratory system frequency response (above 10 Hz) in intubated patients and the patency of the endotracheal tube used to connect the patients to the ventilator.
This study presents a method for quantification of convective transport of a bolus (particle clou... more This study presents a method for quantification of convective transport of a bolus (particle cloud) in the alveolar region. A computational fluid dynamics calculation was performed using a model of a single alveolus connected to a bronchiole. Moving wall boundary conditions and oscillating flow rates in the bronchiole were imposed to mimic breathing conditions. A passive scalar representing the aerosol
Pulmonary cells are normally submitted to large deformations which can become critical in the pat... more Pulmonary cells are normally submitted to large deformations which can become critical in the pathological cases where cells are exposed to both chemical and physical aggressive stresses. These injuries affect among others cell membrane, cytoskeleton structure and cellular functions. The response of cells secondary to such large deformations remains to be understood, whereas the limits for cellular elastic behavior are still under debate. In order to explore these features, we have performed AFM tests which consist in indenting living cells with a long tip over almost the entire cell height (~10 μm). Preliminary results show that the cells exhibit a surprisingly high capability of adaptation without breaking. So, we question in the present study the reasons of such cellular adaptability to large deformations and, more particularly, what mechanical properties at different scales are behind such a specific cellular feature. To understand experimental data, we used two different mechan...
vitro validation of computational fluid dynamics simulation in human proximal airways with hyperp... more vitro validation of computational fluid dynamics simulation in human proximal airways with hyperpolarized 3 He magnetic resonance phase-contrast velocimetry
To explore the determinants of possible collapse of the nasal valve region, a common cause of nas... more To explore the determinants of possible collapse of the nasal valve region, a common cause of nasal obstruction, we evaluated the mechanical properties of the nasal wall. In this study, we determined the nasal cross-sectional area-to-negative pressure ratio (nasal wall compliance) in the anterior part of the nose in six healthy subjects by measuring nasal area by acoustic rhinometry at pressures ranging from atmospheric pressure to a negative pressure of −10 cmH2O. Measurements were performed at baseline and after nasal mucosal decongestion (oxymetazoline). At baseline, nasal wall compliance increased progressively from the nasal valve (0.031 ± 0.016 cm2/cmH2O, mean ± SD) to the anterior and medial part of the inferior turbinate (0.045 ± 0.024 cm2/cmH2O) and to the middle meatus region (0.056 ± 0.029 cm2/cmH2O). After decongestant, compliances decreased and became similar in the three regions. On the basis of these results, we hypothesize that compliance of the nasal wall is partly ...
The sensitivity of alveolar macrophages to substrate properties has been described in a recent pa... more The sensitivity of alveolar macrophages to substrate properties has been described in a recent paper (Féréol et al., Cell Motil. Cytoskel. 63 (2006), 321-340). It is presently re-analyzed in terms of F-actin structure (assessed from 3D-reconstructions in fixed cells) and mechanical properties (assessed by Magnetic Twisting Cytometry experiments in living cells) of cortical and deep cytoskeleton structures for rigid plastic (Young Modulus: 3 MPa) or glass (70 MPa) substrates and a soft (approximately 0.1 kPa) confluent monolayer of alveolar epithelial cells. The cortical cytoskeleton component (lowest F-actin density) is represented by the rapid and softer viscoelastic compartment while the deep cytoskeleton component (intermediate F-actin density) is represented by the slow and stiffer compartment. Stiffness of both cortical and deep cytoskeleton is significantly decreased when soft confluent monolayer of alveolar epithelial cells replace the rigid plastic substrate while F-actin re...
Bioenergetic metabolism is a key regulator of cellular function and signaling, but how it can ins... more Bioenergetic metabolism is a key regulator of cellular function and signaling, but how it can instruct the behavior of cells and their fate during embryonic development remains largely unknown. Here, we investigated the role of glucose metabolism in the development of avian trunk neural crest cells (NCCs), a migratory stem cell population of the vertebrate embryo. We uncovered that trunk NCCs display glucose oxidation as a prominent metabolic phenotype, in contrast to what is seen for cranial NCCs, which instead rely on aerobic glycolysis. In addition, only one pathway downstream of glucose uptake is not sufficient for trunk NCC development. Indeed, glycolysis, mitochondrial respiration and the pentose phosphate pathway are all mobilized and integrated for the coordinated execution of diverse cellular programs, epithelial-to-mesenchymal transition, adhesion, locomotion, proliferation and differentiation, through regulation of specific gene expression. In the absence of glucose, the ...
Les voies aeriennes superieures se caracterisent par une succession de singularites anatomiques e... more Les voies aeriennes superieures se caracterisent par une succession de singularites anatomiques et fonctionnelles (naso/oro/hypopharynx) dont le role specifique est de plus en plus mis en evidence chez les patients apneiques et/ou ronfleurs. Par ailleurs, le debit inspire est fortement altere dans les hypopnees obstructives severes et se presente le plus souvent sous forme de plateau a des valeurs de debit tres diminuees par rapport a celles d'inspirations normales. Le but de la these est premierement la prise en compte des singularites pharyngees par un modele a plusieurs elements compliants individualises, dont un element d'aval controle en pression et un (ou plusieurs) element(s) libre(s) d'amont. Les equations de conservation, differentiees par rapport a la pression de controle, aboutissent a un systeme d'equations qui permet de mettre en evidence, sur les variations de la section d'amont et le debit, le role fondamental des indexes de vitesse associes a la distensibilite, s#1 et s#2 (ou leurs valeurs corrigees en fluide visqueux) respectivement definis pour l'element libre d'amont et l'element controle d'aval dans le modele a deux elements. La condition s#1 = 1 et s#2 = 1 correspond a une condition critique alors que la condition s#1 = 1 et s#2 = 1 correspond au point singulier. Cette derniere condition s'avere jouer un role fondamental dans la generation du plateau de debit qui correspond en fait a une succession de maximum et de minimum de debits rapproches avec passages multiples par le point singulier, dependant du nombre d'elements libres. Le modele a ete valide a partir des resultats obtenus chez l'homme (debit et aire pharyngee mesuree par reflexion acoustique) dans les conditions d'inspiration normale et d'hypopnees obstructives severes. Le modele a deux elements lors d'inspiration orale comme le modele a trois elements propose pour l'inspiration nasale permettent de reproduire, dans des gammes de valeurs physiopathologiques, les limitations de debit en plateau et les variations d'aire pharyngee. Le present modele constitue un outil potentiel pour optimiser les moyens therapeutiques utilises pour reduire les hypopnees obstructives : traitement par pression nasale positive, chirurgie et/ou medicaments.
In this work, a sleep apnea diagnosis system based on Hidden Markov Models (HMMs) is presented. C... more In this work, a sleep apnea diagnosis system based on Hidden Markov Models (HMMs) is presented. Conventional and new simulated annealing based methods for the training of HMMs are incorporated. The inference method of this system translates parameter values into ...
We studied eight heavy snorers with upper airway resistance syndrome to investigate potential eff... more We studied eight heavy snorers with upper airway resistance syndrome to investigate potential effects of sleep on expiratory airway and lung resistance, intrinsic positive end-expiratory pressure, hyperinflation, and elastic inspiratory work of breathing (WOB). Wakefulness and nonrapid-eye-movement sleep with high-and with low-resistance inspiratory effort (H-RIE and L-RIE, respectively) were compared. No differences in breathing pattern were seen across the three conditions. In contrast, we found increases in expiratory airway and lung resistance during H-RIE compared with L-RIE and wakefulness (56 Ϯ 24, 16 Ϯ 4, and 11 Ϯ 4 cmH 2 O•l Ϫ1 • s, respectively), with attendant increases in intrinsic positive end-expiratory pressure (5.4 Ϯ 1.8, 1.4 Ϯ 0.5, and 1.3 Ϯ 1.3 cmH 2 O, respectively) and elastic WOB (6.1 Ϯ 2.2, 3.7 Ϯ 1.2, and 3.4 Ϯ 0.7 J/min, respectively). The increase in WOB during H-RIE is partly caused by the effects of dynamic pulmonary hyperinflation produced by the increased expiratory resistance. Contrary to the Starling model, a multiple-element compliance model that takes into account the heterogeneity of the pharynx may explain flow limitation during expiration.
Le pilote de chasse subit frequemment des accelerations +Gz (accelerations dont les forces d'... more Le pilote de chasse subit frequemment des accelerations +Gz (accelerations dont les forces d'inertie sont dirigees vers les membres inferieurs). Ces accelerations pourraient induire une obstruction des voies aeriennes superieures (VAS) par un mecanoreflexe d'origine pulmonaire, par un deplacement du volume sanguin lingual et pharynge ou par effet mecanique direct de la variation de gravite. Pour definir la contribution de ces trois mecanismes, nous avons evalue, respectivement par plethysmographie a variation d'inductance et par une methode de reflexion acoustique, le volume pulmonaire en fin d'expiration (EEV) et la surface des VAS chez 6 sujets sains en position assise et couchee au cours de periodes de gravite de 0, 1 et 2 +Gz observees lors de vols paraboliques. Lorsque la gravite augmente de 0 a 2 +Gz, on observe, en position assise, une augmentation de la surface des regions palato-pharyngee et retrobasilinguale (+30% et +20% (p < 0.05), respectivement) et d...
We measured upper airway caliber and lung volumes in six normal subjects in the sitting and supin... more We measured upper airway caliber and lung volumes in six normal subjects in the sitting and supine positions during 20-s periods in normogravity, hypergravity [1.8 + head-to-foot acceleration (Gz)], and microgravity (∼0 Gz) induced by parabolic flights. Airway caliber and lung volumes were inferred by the acoustic reflection method and inductance plethysmography, respectively. In subjects in the sitting position, an increase in gravity from 0 to 1.8 +Gz was associated with increases in the calibers of the retrobasitongue and palatopharyngeal regions (+20 and +30%, respectively) and with a concomitant 0.5-liter increase in end-expiratory lung volume (functional residual capacity, FRC). In subjects in the supine position, no changes in the areas of these regions were observed, despite significant decreases in FRC from microgravity to normogravity (−0.6 liter) and from microgravity to hypergravity (−0.5 liter). Laryngeal narrowing also occurred in both positions (about −15%) when gravi...
This report concerns the inference of geometric and mechanical airway characteristics based on in... more This report concerns the inference of geometric and mechanical airway characteristics based on information derived from a single transient planar wave recorded at the airway opening. We describe a new method to simultaneously measure upper airway area and respiratory input impedance by performing dual analysis of a single pressure wave. The algorithms required to reconstruct airway dimensions and mechanical characteristics were developed, implemented, and tested with reference to known physical models. Our method appears suitable to estimate, even under severe intensive care unit conditions, the respiratory system frequency response (above 10 Hz) in intubated patients and the patency of the endotracheal tube used to connect the patients to the ventilator.
This study presents a method for quantification of convective transport of a bolus (particle clou... more This study presents a method for quantification of convective transport of a bolus (particle cloud) in the alveolar region. A computational fluid dynamics calculation was performed using a model of a single alveolus connected to a bronchiole. Moving wall boundary conditions and oscillating flow rates in the bronchiole were imposed to mimic breathing conditions. A passive scalar representing the aerosol
Pulmonary cells are normally submitted to large deformations which can become critical in the pat... more Pulmonary cells are normally submitted to large deformations which can become critical in the pathological cases where cells are exposed to both chemical and physical aggressive stresses. These injuries affect among others cell membrane, cytoskeleton structure and cellular functions. The response of cells secondary to such large deformations remains to be understood, whereas the limits for cellular elastic behavior are still under debate. In order to explore these features, we have performed AFM tests which consist in indenting living cells with a long tip over almost the entire cell height (~10 μm). Preliminary results show that the cells exhibit a surprisingly high capability of adaptation without breaking. So, we question in the present study the reasons of such cellular adaptability to large deformations and, more particularly, what mechanical properties at different scales are behind such a specific cellular feature. To understand experimental data, we used two different mechan...
vitro validation of computational fluid dynamics simulation in human proximal airways with hyperp... more vitro validation of computational fluid dynamics simulation in human proximal airways with hyperpolarized 3 He magnetic resonance phase-contrast velocimetry
To explore the determinants of possible collapse of the nasal valve region, a common cause of nas... more To explore the determinants of possible collapse of the nasal valve region, a common cause of nasal obstruction, we evaluated the mechanical properties of the nasal wall. In this study, we determined the nasal cross-sectional area-to-negative pressure ratio (nasal wall compliance) in the anterior part of the nose in six healthy subjects by measuring nasal area by acoustic rhinometry at pressures ranging from atmospheric pressure to a negative pressure of −10 cmH2O. Measurements were performed at baseline and after nasal mucosal decongestion (oxymetazoline). At baseline, nasal wall compliance increased progressively from the nasal valve (0.031 ± 0.016 cm2/cmH2O, mean ± SD) to the anterior and medial part of the inferior turbinate (0.045 ± 0.024 cm2/cmH2O) and to the middle meatus region (0.056 ± 0.029 cm2/cmH2O). After decongestant, compliances decreased and became similar in the three regions. On the basis of these results, we hypothesize that compliance of the nasal wall is partly ...
The sensitivity of alveolar macrophages to substrate properties has been described in a recent pa... more The sensitivity of alveolar macrophages to substrate properties has been described in a recent paper (Féréol et al., Cell Motil. Cytoskel. 63 (2006), 321-340). It is presently re-analyzed in terms of F-actin structure (assessed from 3D-reconstructions in fixed cells) and mechanical properties (assessed by Magnetic Twisting Cytometry experiments in living cells) of cortical and deep cytoskeleton structures for rigid plastic (Young Modulus: 3 MPa) or glass (70 MPa) substrates and a soft (approximately 0.1 kPa) confluent monolayer of alveolar epithelial cells. The cortical cytoskeleton component (lowest F-actin density) is represented by the rapid and softer viscoelastic compartment while the deep cytoskeleton component (intermediate F-actin density) is represented by the slow and stiffer compartment. Stiffness of both cortical and deep cytoskeleton is significantly decreased when soft confluent monolayer of alveolar epithelial cells replace the rigid plastic substrate while F-actin re...
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