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Cilia are microscopic projections that extend from eukaryotic cells. There are two general types of cilia; primary cilia serve as sensory organelles, whereas motile cilia exert mechanical force. The motile cilia emerging from human airway epithelial cells propel harmful inhaled material out of the lung. We found that these cells express sensory bitter taste receptors, which localized on motile cilia. Bitter compounds increased the intracellular calcium ion concentration and stimulated ciliary beat frequency. Thus, airway epithelia contain a cell-autonomous system in which motile cilia both sense noxious substances entering airways and initiate a defensive mechanical mechanism to eliminate the offending compound. Hence, like primary cilia, classical motile cilia also contain sensors to detect the external environment.

Mammalian lungs are branched networks containing thousands to millions of airways arrayed in intricate patterns that are crucial for respiration. How such trees are generated during development, and how the developmental patterning information is encoded, have long fascinated biologists and mathematicians. However, models have been limited by a lack of information on the normal sequence and pattern of branching events. Here we present the complete three-dimensional branching pattern and lineage of the mouse bronchial tree, reconstructed from an analysis of hundreds of developmental intermediates. The branching process is remarkably stereotyped and elegant: the tree is generated by three geometrically simple local modes of branching used in three different orders throughout the lung. We propose that each mode of branching is controlled by a genetically encoded subroutine, a series of local patterning and morphogenesis operations, which are themselves controlled by a more global master routine. We show that this hierarchical and modular programme is genetically tractable, and it is ideally suited to encoding and evolving the complex networks of the lung and other branched organs. Lung development: Branches everywhere How the massively branched networks of the lung and other organs are generated during development and how the patterning information is encoded have long fascinated biologists and mathematicians. Now the complete branching pattern and branch lineage of the mouse bronchial tree has been determined from an analysis of hundreds of developmental intermediates. The process is remarkably stereotyped and mathematically elegant. The entire tree is generated from three geometrically simple local branching modes used in three different orders. Development proceeds in the manner of a computer program with each mode of branching controlled by a genetically encoded subroutine in a series of local patterning and morphogenesis operations, which are themselves controlled by a more global master routine. A complete three-dimensional branching pattern and lineage of the mouse bronchial tree, reconstructed from an analysis of hundreds of developmental intermediates, is described. The branching process is stereotyped and generated by three simple modes of branching used in three different orders throughout the lung.

There is currently no universally recommended and accepted method of data processing within the science of indirect calorimetry for either mixing chamber or breath-by-breath systems of expired gas analysis. Exercise physiologists were first surveyed to determine methods used to process oxygen consumption (V̇O 2 ) data, and current attitudes to data processing within the science of indirect calorimetry. Breath-by-breath datasets obtained from indirect calorimetry during incremental exercise were then used to demonstrate the consequences of commonly used time, breath and digital filter post-acquisition data processing strategies. Assessment of the variability in breath-by-breath data was determined using multiple regression based on the independent variables ventilation (VE), and the expired gas fractions for oxygen and carbon dioxide, FEO 2 and FECO 2 , respectively. Based on the results of explanation of variance of the breath-by-breath V̇O 2 data, methods of processing to remove variability were proposed for time-averaged, breath averaged and digital filter applications. Among exercise physiologists, the strategy used to remove the variability in sequential V̇O 2 measurements varied widely, and consisted of time averages (30 sec [38%], 60 sec [18%], 20 sec [11%], 15 sec [8%]), a moving average of five to 11 breaths (10%), and the middle five of seven breaths (7%). Most respondents indicated that they used multiple criteria to establish maximum V̇O 2 (V̇O 2max ) including: the attainment of age-predicted maximum heart rate (HR max ) [53%], respiratory exchange ratio (RER) >1.10 (49%) or RER >1.15 (27%) and a rating of perceived exertion (RPE) of >17, 18 or 19 (20%). The reasons stated for these strategies included their own beliefs (32%), what they were taught (26%), what they read in research articles (22%), tradition (13%) and the influence of their colleagues (7%). The combination of VE, FEO 2 and FECO 2 removed 96–98% of V̇O 2 breath-by-breath variability in incremental and steady-state exercise V̇O 2 data sets, respectively. Correction of residual error in V̇O 2 datasets to 10% of the raw variability results from application of a 30-second time average, 15-breath running average, or a 0.04 Hz low cut-off digital filter. Thus, we recommend that once these data processing strategies are used, the peak or maximal value becomes the highest processed datapoint. Exercise physiologists need to agree on, and continually refine through empirical research, a consistent process for analysing data from indirect calorimetry.

The lungs of birds move air in only one direction during both inspiration and expiration through most of the tubular gas-exchanging bronchi (parabronchi), whereas in the lungs of mammals and presumably other vertebrates, air moves tidally into and out of terminal gas-exchange structures, which are cul-de-sacs. Unidirectional flow purportedly depends on bellowslike ventilation by air sacs and may have evolved to meet the high aerobic demands of sustained flight. Here, we show that air flows unidirectionally through parabronchi in the lungs of the American alligator, an amphibious ectotherm without air sacs, which suggests that this pattern dates back to the basal archosaurs of the Triassic and may have been present in their nondinosaur descendants (phytosaurs, aetosaurs, rauisuchians, crocodylomorphs, and pterosaurs) as well as in dinosaurs.

We present a novel image-based technique to estimate a subject-specific boundary condition (BC) for computational fluid dynamics (CFD) simulation of pulmonary air flow. The information of regional ventilation for an individual is derived by registering two computed tomography (CT) lung datasets and then passed to the CT-resolved airways as the flow BC. The CFD simulations show that the proposed method predicts lobar volume changes consistent with direct image-measured metrics, whereas the other two traditional BCs (uniform velocity or uniform pressure) yield lobar volume changes and regional pressure differences inconsistent with observed physiology.

At fertilization, mouse sperm bind to the zona pellucida (which consists of glycoproteins ZP1, ZP2, and ZP3) that surrounds eggs. A ZP2 cleavage model of gamete recognition requires intact ZP2, and a glycan release model postulates that zona glycans are ligands for sperm. These two models were tested by replacing endogenous protein with ZP2 that cannot be cleaved (Zp2Mut) or with ZP3 lacking implicated O glycans (Zp3Mut). Sperm bound to two-cell Zp2Mut embryos despite fertilization and cortical granule exocytosis. Contrary to prediction, sperm fertilized Zp3Mut eggs. Sperm at the surface of the zona pellucida remained acrosome-intact for more than 2 hours and were displaced by additional sperm. These data indicate that sperm-egg recognition depends on the cleavage status of ZP2 and that binding at the surface of the zona is not sufficient to induce sperm acrosome exocytosis.

The geometry and dimensions of branched structures such as blood vessels or airways are important factors in determining the efficiency of physiological processes. It has been shown that fractal trees can be space filling 1 and can ensure minimal dissipation 2 , 3 , 4 . The bronchial tree of most mammalian lungs is a good example of an efficient distribution system with an approximate fractal structure 5 , 6 . Here we present a study of the compatibility between physical optimization and physiological robustness in the design of the human bronchial tree. We show that this physical optimization is critical in the sense that small variations in the geometry can induce very large variations in the net air flux. Maximum physical efficiency therefore cannot be a sufficient criterion for the physiological design of bronchial trees. Rather, the design of bronchial trees must be provided with a safety factor and the capacity for regulating airway calibre. Paradoxically, our results suggest that bronchial malfunction related to asthma is a necessary consequence of the optimized efficiency of the tree structure.

Human trachea is a multi-component structure composed of cartilage, trachealis muscle, mucosa and submucosa membrane and adventitial membrane. Its mechanical properties are essential for an accurate prediction of tracheal deformation, which has a significant clinic relevance. Efforts have been made in quantifying the material behaviour of tracheal cartilage and trachealis muscle. However, the material behaviours of other components have been least investigated. Three human cadaveric trachea specimens were used in this study. Trachealis muscle, mucosa and submucosa membrane and adventitia membrane were excised to perform the uniaxial test in axial and circumferential directions. In total, 72 tissue strips were prepared and tested. Tangent modulus was used to quantified the stiffness of each tissue strip at various stretch levels. The obtained results indicated that all types of tracheal soft tissues were highly non-linear and anisotropic. Trachealis muscle in the circumferential direction had the most excellent extensibility; and the adventitial collagen membrane in the circumferential direction was the stiffest. This study is helpful in understanding the material behaviour of trachea. Obtained results can be used for computational and analytic modelling to quantify the tracheal deformation.

This study reconstructed a three dimensional fluid/structure interaction (FSI) model to investigate the compliance of human soft palate during calm respiration. Magnetic resonance imaging scans of a healthy male subject were obtained for model reconstruction of the upper airway and the soft palate. The fluid domain consists of nasal cavity, nasopharynx and oropharynx. The airflow in upper airway was assumed as laminar and incompressible. The soft palate was assumed as linear elastic. The interface between airway and soft palate was the FSI interface. Sinusoidal variation of velocity magnitude was applied at the oropharynx corresponding to ventilation rate of 7.5L/min. Simulations of fluid model in upper airway, FSI models with palatal Young's modulus of 7539Pa and 3000Pa were carried out for two cycles of respiration. The results showed that the integrated shear forces over the FSI interface were much smaller than integrated pressure forces in all the three directions (axial, coronal and sagittal). The total integrated force in sagittal direction was much smaller than that of coronal and axial directions. The soft palate was almost static during inspiration but moved towards the posterior pharyngeal wall during expiration. In conclusion, the displacement of human soft palate during respiration was mainly driven by air pressure around the surface of the soft palate with minimal contribution of shear stress of the upper airway flow. Despite inspirational negative pressure, expiratory posterior movement of soft palate could be another factor for the induction of airway collapse.