Administration of vitamin E attenuates airway inflammation through restoration of Nrf2 in a mouse model of asthma

Accumulating evidence reveals that ROS is one of the key mediators that contribute to the development of asthma. Studies on antioxidants have shown to have beneficial effects on asthma management. However, we still do not know the precise mechanism, and the effects depend on age. This study was conducted to assess the levels of ROS and the effect of antioxidants in younger and older mice using an eosinophilic asthma model. We analyzed airway hyperresponsiveness (AHR), cytokines in bronchoalveolar lavage fluid (BALF), inflammatory cell counts, and the expression levels of NFκB, Nrf2, EPx, and EDN in the lung tissue, as well as the level of ROS in the lung tissue and BALF. The degree of eosinophilia and the levels of IL-5, ROS, and NFκB were significantly increased, whereas the endogenous levels of vitamin E and Nrf2 were decreased in the lung and BALF in the older mice compared to younger mice. The administration of vitamin E attenuated AHR, airway inflammation, and the level of IL-13 and ROS and enhanced the Nrf2 level in the older mice compared to the younger mice. Taken together, vitamin E treatment may have the therapeutic potential through restoration of the Nrf2 level, especially in elderly asthma.     

Spatial distribution of acoustic and elastic properties of human femoral cortical bone

The purpose of this study is to quantify the spatial distribution of acoustic velocities and elastic properties (elastic constants) on Human femoral cortical bone. Four cross sections (average thickness of 2.09+/-0.27 mm) have been cut transversally between 40% and 70% of the total length and between them parallelepiped samples in each quadrant have been cut. Ultrasonic technique in transmission with immersion focused transducers at 5 MHz and contact transducers 2.25 MHz were used on the cross sections and parallelepiped samples, respectively. The first technique allows relative spatial distribution of velocities to be obtained, meanwhile the second technique allows the direct assessment of elastic constants. For both techniques, bulk velocities were found to be lower at the posterior side with an increase along the length (from 40% to 70% total length) (p < 0.05). Densities and elastic constants show equivalent pattern of variation. These variations are mainly due the cortical porosity related to vascularisation environment. The spatial distribution of velocities exhibits significant radial variation from the endosteal to the periosteal region. This is in agreement with variation of the porosity at that location. Same range of velocities was obtained with both techniques. The range of longitudinal velocities values varies from 3548 to 3967 m/s and between 18.5 and 33.1 GPa for the bulk velocities and axial elastic constants, respectively. Our results are within the range with those found in the literature. However, it must be noted that the range of acoustic and elastic properties variation is concerning the same bone. So, our new results show the ability of the technique to quantify accurately local variation of acoustic and elastic properties (within the section and along the length) of human cortical bone. Furthermore, our immersion technique could be used to assess the spatial distribution of the elastic constants with the knowledge of spatial distribution of densities.     

Tocopherol long chain fatty alcohols decrease the production of TNF-α and NO radicals by activated microglial cells

The synthesis of a series of Tocopherol long chain Fatty Alcohols (TFA) and their biological activities on the modulation of microglial activation are described. Specifically, the 2-(12-hydroxy-dodecyl)-2,5,7,8-tetramethyl-chroman-6-ol, the TFA bearing 12 carbon atoms on the side chain (n=12), shows the most potent inhibition of secretion on nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha) by lipopolysaccharide (LPS)-activated microglia.     

Time-Dependent Increase in Network Response to Stimulation

In vitro neuronal cultures have become a popular method with which to probe network-level neuronal dynamics and phenomena in controlled laboratory settings. One of the key dynamics of interest in these in vitro studies has been the extent to which cultured networks display properties indicative of learning. Here we demonstrate the effects of a high frequency electrical stimulation signal in training cultured networks of cortical neurons. Networks receiving this training signal displayed a time-dependent increase in the response to a low frequency probing stimulation, particularly in the time window of 20–50 ms after stimulation. This increase was found to be statistically significant as compared to control networks that did not receive training. The timing of this increase suggests potentiation of synaptic mechanisms. To further investigate this possibility, we leveraged the powerful Cox statistical connectivity method as previously investigated by our group. This method was used to identify and track changes in network connectivity strength.     

Improved intracellular delivery of glucocerebrosidase mediated by the HIV-1 TAT protein transduction domain

Enzyme replacement therapy (ERT) for Gaucher disease designed to target glucocerebrosidase (GC) to macrophages via mannose-specific endocytosis is very effective in reversing hepatosplenomegaly, and normalizing hematologic parameters but is less effective in improving bone and lung involvement and ineffective in brain. Recombinant GCs containing an in-frame fusion to the HIV-1 trans-activator protein transduction domain (TAT) were expressed in eukaryotic cells in order to obtain active, normally glycosylated GC fusion proteins for enzyme uptake studies. Despite the absence of mannose-specific endocytic receptors on the plasma membranes of various fibroblasts, the recombinant GCs with C-terminal TAT fusions were readily internalized by these cells. Immunofluorescent confocal microscopy demonstrated the recombinant TAT-fusion proteins with a mixed endosomal and lysosomal localization. Thus, TAT-modified GCs represent a novel strategy for a new generation of therapeutic enzymes for ERT for Gaucher disease.     

Aquaporin Trafficking in Plant Cells: An Emerging Membrane‐Protein Model

Aquaporins (AQPs) are channel proteins that facilitate the transport of water and small solutes across biological membranes. In plants, AQPs exhibit a high multiplicity of isoforms in relation to a high diversity of sub‐cellular localizations, at the plasma membrane (PM) and in various intracellular compartments. Some members also exhibit a dual localization in distinct cell compartments, whereas others show polarized or domain‐specific expression at the PM or tonoplast, respectively. A diversity of mechanisms controlling the routing of newly synthesized AQPs towards their destination membranes and involving diacidic motifs, phosphorylation or tetramer assembly is being uncovered. Recent approaches using single particle tracking, fluorescence correlation spectroscopy and fluorescence recovery after photobleaching have, in combination with pharmacological interference, stressed the peculiarities of AQP sub‐cellular dynamics in environmentally challenging conditions. A role for clathrin and sterol‐rich domains in cell surface dynamics and endocytosis of PM AQPs was uncovered. These recent advances provide deep insights into the cellular mechanisms of water transport regulation in plants. They also point to AQPs as an emerging model for studying the sub‐cellular dynamics of plant membrane proteins .     

Review: microbial mechanisms of accessing insoluble Fe(III) as an energy source

Of all the terminal electron acceptors, Fe(III) is the most naturally abundant in many subsurface environments. Fe(III)-reducing microorganisms are phylogenetically diverse and have been isolated from a variety of sources. Unlike most electron acceptors, Fe(III) has a very low solubility and is usually present as insoluble oxides at neutral pH. The mechanisms by which microorganisms access and reduce insoluble Fe(III) are poorly understood. Initially, it was considered that microorganisms could only reduce insoluble Fe(III) through direct contact with the oxide. However, recent studies indicate that extracellular electron shuttling or Fe(III)-chelating compounds may alleviate the need for cell–oxide contact. These include microbially secreted compounds or exogenous electron shuttling agents, mainly from humic substances. Electron shuttling via humic substances is likely a significant process for Fe(III) reduction in subsurface environments. This paper reviews the various mechanisms by which Fe(III) reduction may be occurring in pure culture and in soils and sediments.