The Rho Pathway Mediates Transition to an Alveolar Type I Cell Phenotype During Static Stretch of Alveolar Type II Cells

Stretch is an essential mechanism for lung growth and development. Animal models in which fetal lungs have been chronically over or underdistended demonstrate a disrupted mix of type II and type I cells, with static overdistention typically promoting a type I cell phenotype. The Rho GTPase family, key regulators of cytoskeletal signaling, are known to mediate cellular differentiation in response to stretch in other organs. Using a well-described model of alveolar epithelial cell differentiation and a validated stretch device, we investigated the effects of supraphysiologic stretch on human fetal lung alveolar epithelial cell phenotype. Static stretch applied to epithelial cells suppressed type II cell markers (SP-B and Pepsinogen C, PGC), and induced type I cell markers (Caveolin-1, Claudin 7 and Plasminogen Activator Inhibitor-1, PAI-1) as predicted. Static stretch was also associated with Rho A activation. Furthermore, the Rho kinase inhibitor Y27632 decreased Rho A activation and blunted the stretch-induced changes in alveolar epithelial cell marker expression. Together these data provide further evidence that mechanical stimulation of the cytoskeleton and Rho activation are key upstream events in mechanotransduction-associated alveolar epithelial cell differentiation

Diaphragm Mechanics in Dogs With Unilateral Emphysema

We studied dogs with unilateral papain-induced emphysema to answer two questions: (1) Do emphysema lung-apposed hemidiaphragm (DiE) and normal lung-apposed hemidiaphragm (DiN) have equal capacities for lowering lung surface pressure? and (2) Are side-to-side differences in intrathoracic pressure the result of unequal force outputs by DiE and DiN or are they caused by differences in their mechanical efficiency as pressure generators? After the airways of the emphysematous and normal lungs were intubated with a dual lumen endotracheal tube, both phrenic nerves were maximally stimulated at rates between 1 and 50 Hz and the changes in airway occlusion pressure (delta PaoE,N) and diaphragm length (sonomicrometry) were recorded. In all animals, delta PaoN exceeded delta PaoE. Differences in pressure ranged from 1.2 +/- 0.6 cm H2O during a twitch to 6.0 +/- 2.9 cm H2O during a 50-Hz tetanus. Midcostal bundles of DiE shortened less than corresponding bundles of DiN, but both reached the same active length relative to their optimal lengths, which were measured in vitro. There was no significant difference in fiber type distribution, fiber cross-sectional area, or maximal isometric tetanic tensions among midcostal regions of DiE and DiN. We conclude that unilateral hyperinflation impairs the mechanical efficiency of the apposing hemidiaphragm as a pressure generator

Infrared spectroscopy of phytochrome and model pigments

Fourier-transform infrared difference spectra between the red-absorbing and far-red-absorbing forms of oat phytochrome have been measured in H2O and 2H2O. The difference spectra are compared with infrared spectra of model compounds, i.e. the (5Z,10Z,15Z)- and (5Z,10Z,15E)-isomers of 2,3,7,8,12,13,17,18-octaethyl-bilindion (Et8-bilindion), 2,3-dihydro-2,3,7,8,12,13,17,18-octaethyl-bilindion (H2Et8-bilindion), and protonated H2Et8-bilindion in various solvents. The spectra of the model compounds show that only for the protonated forms can clear differences between the two isomers be detected. Since considerable differences are present between the spectra of Et8-bilindion and H2Et8-bilindion, it is concluded that only the latter compound can serve as a model system of phytochrome. The 2H2O effect on the difference spectrum of phytochrome supports the view that the chromophore in red-absorbing phytochrome is protonated and suggests, in addition, that it is also protonated in far-red-absorbing phytochrome. The spectra show that protonated carboxyl groups are influenced. The small amplitudes in the difference spectra exclude major changes of protein secondary structure

Disentangling cortical functional connectivity strength and topography reveals divergent roles of genes and environment

The human brain varies across individuals in its morphology, function, and cognitive capacities. Variability is particularly high in phylogenetically modern regions associated with higher order cognitive abilities, but its relationship to the layout and strength of functional networks is poorly understood. In this study we disentangled the variability of two key aspects of functional connectivity: strength and topography. We then compared the genetic and environmental influences on these two features. Genetic contribution is heterogeneously distributed across the cortex and differs for strength and topography. In heteromodal areas genes predominantly affect the topography of networks, while their connectivity strength is shaped primarily by random environmental influence such as learning. We identified peak areas of genetic control of topography overlapping with parts of the processing stream from primary areas to network hubs in the default mode network, suggesting the coordination of spatial configurations across those processing pathways. These findings provide a detailed map of the diverse contribution of heritability and individual experience to the strength and topography of functional brain architecture.Nanyang Technological UniversityPublished versionThis work was supported by the Medical University of Vienna, the Austrian Research Fund (FWF) [grants P 35189, P 34198, and I 3925-B27] in collaboration with the French National Research Agency (ANR), the Vienna Science and Technology Fund (WWTF) [LS20-065], the European Research Council Grant [866533-CORTIGRAD], the National Natural Science Foundation of China [Grant No. 81790652, No.81790650] and the NAM Advanced Biomedical Imaging Program [FY2016] between Nanyang Technological University, Singapore and Medical University of Vienna, Austria

Measurement of Forward Jets Produced in High-Transverse-Momentum Hadron-Proton Collisions

A measurement of charged-particle production is reported for the forward region in events triggered by high-transverse-momentum (p⊥) jets and single particles. The momentum distributions of forward-going particles are observed to scale in a simple p⊥-dependent longitudinal variable. Forward-going (beam) jets are observed to be tilted away from the original direction by an amount which agrees with muon-pair data when interpreted in a parton (quantum-chromodynamics) model

Jets Produced in π^-, π^+, and Proton Interactions at 200 GeV on Hydrogen and Aluminum Targets

This paper presents results from an experiment on the production of jets (groups of particles) with high p_⊥ produced in 200-GeV/c interactions. Results are presented on the comparison of jet cross sections on aluminum and hydrogen targets. The jet fragmentation distributions are also examined. Both the cross section and the jet structure are found to depend strongly on the beam and target types

Observation of the Production of Jets of Particles at High Transverse Momentum and Comparison with Inclusive Single-Particle Reactions

Data are presented on production by 200-GeV/c hadrons incident on beryllium of both single particles and jets (groups of particles) with high p_T (transverse momentum). The experiment was performed in a wide-aperture multiparticle spectrometer at Fermilab. The jet and single-particle cross sections have a similar shape from p_T=3 to 5 GeV/c but the jet cross section is over two orders of magnitude larger. The distributions of charged-particle momenta show striking similarities to those observed in lepton-induced processes

Experimental Tests of Quantum Chromodynamics in High-p_⊥ Jet Production in 200-GeV/c Hadron-Proton Collisions

Data on inclusive jet production in the transverse-momentum (p_⊥) range 0-8 GeV/c for 200-GeV/c p, π^-, π^+, K^-, K^+, and p incident on a hydrogen target are presented. The jet cross section is fully corrected for losses and biases, and compared with the predictions of a model based on quantum chromodynamics. Both the absolute cross section and the inclusive charged-particle distributions inside and outside the jet are in qualitative agreement with the model