Cystic fibrosis: An inherited disease affecting mucin-producing organs

Our current understanding of cystic fibrosis (CF) has revealed that the biophysical properties of mucus play a considerable role in the pathogenesis of the disease in view of the fact that most mucus-producing organs are affected in CF patients. In this review, we discuss the potential causal relationship between altered cystic fibrosis transmembrane conductance regulator (CFTR) function and the production of mucus with abnormal biophysical properties in the intestine and lungs, highlighting what has been learned from cell cultures and animal models that mimic CF pathogenesis. A similar cascade of events, including mucus obstruction, infection and inflammation, is common to all epithelia affected by impaired surface hydration. Hence, the main structural components of mucus, namely the polymeric, gel-forming mucins, are critical to the onset of the disease. Defective CFTR leads to epithelial surface dehydration, altered pH/electrolyte composition and mucin concentration. Further, it can influence mucin transition from the intracellular to extracellular environment, potentially resulting in aberrant mucus gel formation. While defective HCO3− production has long been identified as a feature of CF, it has only recently been considered as a key player in the transition phase of mucins. We conclude by examining the influence of mucins on the biophysical properties of CF sputum and discuss existing and novel therapies aimed at removing mucus from the lungs

SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo

The spike D614G substitution is prevalent in global SARS-CoV-2 strains, but its effects on viral pathogenesis and transmissibility remain unclear. We engineered a SARS-CoV-2 variant containing this substitution. The variant exhibits more efficient infection, replication, and competitive fitness in primary human airway epithelial cells, but maintains similar morphology and in vitro neutralization properties, compared with the ancestral wild-type virus. Infection of human angiotensin-converting enzyme 2 (ACE2) transgenic mice and Syrian hamsters with both viruses resulted in similar viral titers in respiratory tissues and pulmonary disease. However, the D614G variant transmits significantly faster and displayed increased competitive fitness than the wild-type virus in hamsters. These data show that the D614G substitution enhances SARS-CoV-2 infectivity, competitive fitness, and transmission in primary human cells and animal models

Cystic fibrosis: An inherited disease affecting mucin-producing organs

AbstractOur current understanding of cystic fibrosis (CF) has revealed that the biophysical properties of mucus play a considerable role in the pathogenesis of the disease in view of the fact that most mucus-producing organs are affected in CF patients. In this review, we discuss the potential causal relationship between altered cystic fibrosis transmembrane conductance regulator (CFTR) function and the production of mucus with abnormal biophysical properties in the intestine and lungs, highlighting what has been learned from cell cultures and animal models that mimic CF pathogenesis. A similar cascade of events, including mucus obstruction, infection and inflammation, is common to all epithelia affected by impaired surface hydration. Hence, the main structural components of mucus, namely the polymeric, gel-forming mucins, are critical to the onset of the disease. Defective CFTR leads to epithelial surface dehydration, altered pH/electrolyte composition and mucin concentration. Further, it can influence mucin transition from the intracellular to extracellular environment, potentially resulting in aberrant mucus gel formation. While defective HCO3− production has long been identified as a feature of CF, it has only recently been considered as a key player in the transition phase of mucins. We conclude by examining the influence of mucins on the biophysical properties of CF sputum and discuss existing and novel therapies aimed at removing mucus from the lungs.This article is part of a Directed Issue entitled: Cystic Fibrosis: From o-mics to cell biology, physiology, and therapeutic advances

Structural Determinants of the Sign of the Pyroelectric Effect in Quasi-Amorphous SrTiO3 Films

The magnitude and direction of the permanent electric polarization in the non-crystalline, polar phase (termed quasi-amorphous) of SrTiO3 in Si\SiO2\Me\SrTiO3\Me, (Me = Cr or W), Si\SrRuO3\SrTiO3, and Si\SrTiO3 layered structures were investigated. Three potential sources of the polarization which appears after the material is pulled through a temperature gradient were considered: a) contact potential difference; b) a fl exoelectric effect due to a strain gradient caused by substrate curvature; and c) a fl exoelectric effect due to the thermally induced strain gradient that develops while pulling through the steep temperature gradient. Measurements show that options a) and b) can be eliminated from consideration. In most cases studied in this (Si\SrTiO3, Si\SiO2\Me\SrTiO3\Me, M = Cr or W) and previous works (Si\BaTiO3, Si\BaZrO3), the top surface of the quasi-amorphous phase acquires a negative charge upon heating. However, in Si\SrRuO3\SrTiO3 structures the top surface acquires a positive charge upon heating. On the basis of the difference in the measured expansion of the upper and lower surfaces of the SrTiO3 layer in the presence and absence of SrRuO3, we contend that the magnitude and direction of the pyroelectric effect are determined by the out-of-plane gradient of the in-plane strain in the SrTiO3 layer while pulling through the temperature gradient

(Invited) Naked Eye Blue Emission in Ce 3+ Codoped SiO x N y : Toward Si-Based Light-Emitting Devices

International audienceRare earth (RE) doped silicon host matrices has been broadly investigated to procure light emitting sources for integrated optoelectronics devices using the RE inter-4f transitions. Classically, those transitions are partially allowed and result in a very low absorption cross section inducing a non-efficient excitation. Due to its 5d-4f transitions, Ce 3+ ion is quite different from other RE 3+ ions due to a large absorption cross section (10 -19 cm -2 ) as compared to the other RE 3+ ions (10 -21 cm -2 ). [1] Furthermore, due to its single valence d -orbital electron, the 5 d band is strongly dependent on the local environment, resulting typically in a large Stokes shift depending on the host matrix composition. [2] Ce-doped SiO x N y films have been deposited by magnetron reactive sputtering from Si and CeO 2 targets under nitrogen reactive gas atmosphere, with a typical thickness of 120 nm. Three investigation approaches were explored. In the first one samples grown with nitrogen highly rich plasma and a low Ce concentration (0.3 at.%) were tested. Photoluminescence (PL) experiments show a wide blue emission band ranging from 400 to 650 nm under UV photons excitation. Reference samples grown with lower nitrogen content did not show any visible emission. To explain the blue emission origin, we have studied extensively the role of different RE ions emitting centers in Ce-doped SiO x N y films ( e.g. band tails, CeO 2 , Ce clusters, Ce 3+ ions), with different activation scenarios. The results confirmed that blue emission is mainly due to the Ce 3+ ion. In addition, based on refractive index measurements, the Ce-doped SiO x N y films compositions were deduced from a Bruggeman effective medium model, confirming the presence of Si 3 N 4 and SiO 2 phases. Furthermore, the presence of those phases was confirmed independently by their bonding signatures identified by infrared spectroscopy (FTIR) analysis. By means of photoluminescence excitation spectroscopy (PLE), a wide excitation range from 250 to 400 nm was evidenced and various excitation channels of Ce 3+ ions involving direct or indirect mechanisms were proposed. In the second approach, we focused on samples grown at high nitrogen flow, where the effect of Ce 3+ concentration variation was investigated. Under UV excitation, a strong blue emission is visible to the naked eyes for SiO x N y sample doped with high Ce 3+ concentration (6 at. % as determined by RBS measurements). The external quantum efficiency was measured for the selected best emitting samples with help of integrating sphere. No saturation of the PL intensity was observed, demonstrating the absence of Ce clusters and/or silicate phase formation due do the nitrogen content. [3] We believe that this result is very promising for considering silicon based emitting applications. Finally, in the third approach we measured electroluminescence (EL) from Ce-doped SiO x N y prototype devices. Signal evolution was investigated as the function of the N flow, the Ce concentration and the inclusion of Al dopants with the aim to improve the electrical conductivity. The influence of these factors on observed EL was studied through the conduction mechanisms. [1] J.M. Ramírez, A. Ruiz-Caridad, J. Wojcik, A.M. Gutierrez, S. Estradé, F. Peiró, P. Sanchís, P. Mascher, B. Garrido, "Luminescence properties of Ce3+ and Tb3+ co-doped SiOxNy thin films: Prospects for color tunability in silicon-based hosts", J. Appl. Phys., 119 ( 2016 ) 113108. [2] J. Li, O.H.Y. Zalloum, T. Roschuk, C.L. Heng, J. Wojcik, P. Mascher, "Light Emission from Rare-Earth Doped Silicon Nanostructures", Advances in Optical Technologies, 2008 ( 2008 ) 10. [3] C. Labbé, Y.T. An, G. Zatryb, X. Portier, A. Podhorodecki, P. Marie, C. Frilay, J. Cardin, F. Gourbilleau, "Structural and emission properties of Tb 3+ -doped nitrogen-rich silicon oxynitride films", Nanotech., 28 ( 2017 ) 115710 (115714pp)

Source of Electrofreezing of Supercooled Water by Polar Crystals

Polar crystals, which display pyroelectricity, have a propensity to elevate, in a heterogeneous nucleation, without epitaxy, the freezing temperature of supercooled water (SCW). Upon cooling, such crystals accumulate an electric charge at their surfaces, which creates weak electric fields, –1, that are thousands of times lower than necessary for inducing homogeneous ice nucleation. By performing comparative freezing experiments of SCW on the same surfaces of three different polar crystals of amino acids, we demonstrate that preventing the formation of charge at these surfaces, by linking the two hemihedral faces of the polar crystals with a conducting paint, reduces the temperature of freezing by 2–5 °C. The temperature of ice nucleation was found to be correlated with the amount of the surface charge, thus implying that the surface-charge-induced interactions affect the interfacial water molecules that trigger freezing at a higher temperature. This finding is in contrast to previous hypotheses, which attribute the enhanced SCW freezing to the effect of the electric field or capture of external ions or particles. Possible implications of this mechanism of freezing are presented

Impedance Spectroscopic Indication for Solid State Electrochemical Reaction in (CH₃NH₃)PbI₃ Films

Halide perovskite-based solar cells still have limited reproducibility, stability, and incomplete understanding of how they work. We track electronic processes in [CH₃NH₃]­PbI₃(Cl) (“perovskite”) films <i>in vacuo</i>, and in N₂, air, and O₂, using impedance spectroscopy (IS), contact potential difference, and surface photovoltage measurements, providing direct evidence for perovskite sensitivity to the ambient environment. Two major characteristics of the perovskite IS response change with ambient environment, viz. -1- appearance of negative capacitance <i>in vacuo</i> or post<i>-vacuo</i> N₂ exposure, indicating for the first time an electrochemical process in the perovskite, and -2- orders of magnitude decrease in the film resistance upon transferring the film from O₂-rich ambient atmosphere to vacuum. The same change in ambient conditions also results in a 0.5 V decrease in the material work function. We suggest that facile adsorption of oxygen onto the film dedopes it from n-type toward intrinsic. These effects influence any material characterization, i.e., results may be ambient-dependent due to changes in the material’s electrical properties and electrochemical reactivity, which can also affect material stability