Claramines: A New Class Of Broad‐Spectrum Antimicrobial Agents With Bimodal Activity

The emergence of multidrug‐resistant bacteria and pathogens has created an urgent need for the development of new antibiotics. Herein we report our investigations into the broad‐spectrum activity of an easily prepared water‐soluble polyaminosterol compound, namely claramine A1, against both drug‐sensitive and drug‐resistant Gram‐negative and Gram‐positive bacterial strains. We also report its peculiar mechanism of action, which differs from that of all the other well‐known classes of antibiotics, toward Gram‐negative and Gram‐positive bacteria. Given their low cytotoxicity, this class of compounds based on claramine A1 could constitute an effective response to combat the emergence of multidrug‐resistant bacteria and nosocomial diseases.     

Silica nanoparticles inhibit the cation channel TRPV4 in airway epithelial cells

Background

Silica nanoparticles (SiNPs) have numerous beneficial properties and are extensively used in cosmetics and food industries as anti-caking, densifying and hydrophobic agents. However, the increasing exposure levels experienced by the general population and the ability of SiNPs to penetrate cells and tissues have raised concerns about possible toxic effects of this material. Although SiNPs are known to affect the function of the airway epithelium, the molecular targets of these particles remain largely unknown. Given that SiNPs interact with the plasma membrane of epithelial cells we hypothesized that they may affect the function of Transient Receptor Potential Vanilloid 4 (TRPV4), a cation-permeable channel that regulates epithelial barrier function. The main aims of this study were to evaluate the effects of SiNPs on the activation of TRPV4 and to determine whether these alter the positive modulatory action of this channel on the ciliary beat frequency in airway epithelial cells.

Results

Using fluorometric measurements of intracellular Ca²⁺ concentration ([Ca²⁺]_i) we found that SiNPs inhibit activation of TRPV4 by the synthetic agonist GSK1016790A in cultured human airway epithelial cells 16HBE and in primary cultured mouse tracheobronchial epithelial cells. Inhibition of TRPV4 by SiNPs was confirmed in intracellular Ca²⁺ imaging and whole-cell patch-clamp experiments performed in HEK293T cells over-expressing this channel. In addition to these effects, SiNPs were found to induce a significant increase in basal [Ca²⁺]_i, but in a TRPV4-independent manner. SiNPs enhanced the activation of the capsaicin receptor TRPV1, demonstrating that these particles have a specific inhibitory action on TRPV4 activation. Finally, we found that SiNPs abrogate the increase in ciliary beat frequency induced by TRPV4 activation in mouse airway epithelial cells.

Conclusions

Our results show that SiNPs inhibit TRPV4 activation, and that this effect may impair the positive modulatory action of the stimulation of this channel on the ciliary function in airway epithelial cells. These findings unveil the cation channel TRPV4 as a primary molecular target of SiNPs.

     

Helping families move: Relocation counseling for housing-voucher recipients

As the U.S. Department of Housing and Urban Development (HUD) shifts its emphasis from project-based subsidies to housing vouchers, a key question is the amount of relocation help that should be provided to voucher recipients. To address these and related issues, this article examines the use of and influence of relocation counseling at four distressed federally subsidized housing developments (in Baltimore, Maryland; Newport News, Virginia; Kansas City, Missouri; and San Francisco, California) where families were provided with vouchers and relocation counseling in order to expedite moves into the private housing market. Both qualitative and quantitative analysis techniques were used to examine the different approaches to relocation counseling provided by four types of providers: 1) community-based non-profit housing agencies; 2) a private company and its subcontractor, an out-of-town consultant specializing in relocation counseling; 3) a state housing agency; and 4) the on-site housing management company. Underutilization of relocation counseling was a problem: only two-fifths of the sample reported using relocation services. Middle-aged tenants and those at the Baltimore site were most likely to take advantage of the services; those living in overcrowded units were least likely. Programs need to be developed to increase participation rates while recognizing that tenant involvement must remain voluntary in nature at such sites. Although there was some evidence that the more intensive relocation counseling provided in Newport News opened up more housing options for residents, in general the counseling had limited impact. Those who used relocation counseling did not consider more housing options than others, nor were they more likely to focus their housing search on distant neighborhoods. Furthermore, residents depended on friends and relatives, rather than relocation counselors, to learn about their new home. Even though many respondents made short-distance moves (especially in Baltimore and Kansas City), they usually were able to improve their housing and neighborhood conditions. These findings suggest that it may be unreasonable to expect families-particularly those relying on public transportation—to relocate to new and unfamiliar neighborhoods without support, or without intensive counseling, encouraging them to do so. Spatial deconcentration may not always be an appropriate goal for all voucher recipients. David P. Varady co-principal investigator, Professor of Planning is Professor of Planning at the University of Cincinnati. Professor Varady has written widely about community conservation and housing policy, both in the United States and the United Kingdom. His most recent book, co-edited with Wolfgang F.E. Preiser and Francis P. Russell,New Directions in Urban Public Housing, was published by the Center for Urban Policy Research, Fall, 1988. Carole C. Walker co-principal investigator, is Assistant Director of the Center for Urban Policy Research at Rutgers University. In her years at the Center, she has studied a broad range of public policy issues, including program evaluation, affordable housing,subdivision regulations, and land use development. She is the author of numerous research studies and co-author with David Listokin ofThe Subdivision and Site Plan Handbook. Kirk McClure investigator, is an Associate Professor with the Graduate Program in Urban Planning at the University of Kansas. His teaching and research interests are in the areas of housing and community development. He has recently completed research evaluating the ten-year performance of the Low-Income Housing Tax Credit program and is now engaged in an examination of the secondary mortgage market as an aid to affordable housing. Janet Smith-Heimer, investigator, is the founding principal of Bay Area Economics (BAE), a national consulting firm specializing in urban and real estate economics. She has been actively engaged in urban development since 1978 and has developed expertise in affordable housing, economic development, and military base closure. Sherry Larkins research assistant, is a Ph.D. candidate in sociology at Rutgers University. Her areas of interest are race relations, urban sociology, and substance abuse.     

Immunocytochemical localisation of para-coumaric acid and feruloyl-arabinose in the cell walls of maize stem

Two phenolic compounds, p-coumaric acid and feruloyl-arabinose, were localised by immunocytochemistry in the cell walls of the apical internode of two lines of maize (Co125 and W401) of different digestibility. The compounds were detected at two stages of cell maturity in the lignified tissues (sclerenchyma, fibres and xylem) and in the medullary parenchyma, which, in the samples studied, was not lignified. p-Coumaric acid is a phenolic acid associated with lignins, which confer resistance on plant cell walls to microbial degradation in the rumen. Feruloyl-arabinose is a compound associated with xylans, the principal hemicelluloses in Gramineae, which are potentially degradable. Labelling of p-coumaric acid decreased in both maize lines with cell age and as the cell walls became lignified. The mass of lignin deposited in the cell walls masked p-coumaric acid, thereby making it less accessible to the antibodies. There was an inverse relationship in the labelling of p-coumaric acid and feruloyl-arabinose. Feruloyl-arabinose was more heavily labelled as the plant cell walls matured in all the lignified tissues of both maize lines and in the parenchyma of the less digestible line. All tissues except the parenchyma were more heavily labelled with both sera in Co125, the more digestible line. © 1998 Society of Chemical Industry.     

Production and Corrosion Resistance of Thermally Sprayed Fe-Based Amorphous Coatings from Mechanically Milled Feedstock Powders

Mechanically milled FeCrNbB feedstock powders from commercial precursors were used to produce amorphous coatings through two different industrial thermal-spraying techniques: high-velocity oxygen fuel (HVOF) and flame spraying. Microstructure, thermal behavior, and hardness of the coatings and their corrosion resistances in acidic and alkaline chloride-rich media were comparatively studied. HVOF process was effective to produce ~ 200-µm-thick highly amorphous coatings with hardness over than 700 HV_0.3 and low porosity (~ 5 pct). Flame-sprayed ~ 220-µm-thick coatings were nanocrystalline, composed of α-Fe, Fe₂B, FeNbB, and Fe₂O₃ phases and presented hardness of 564 HV_0.3 and ~ 10 pct porosity. Electrochemical measurements indicated that HVOF coatings exhibit higher corrosion resistance than flame-sprayed ones thanks to the higher amorphous content and lower porosity resulting from the former processing route. Electrochemical impedance spectroscopy results demonstrated that amorphous HVOF Fe₆₀Cr₈Nb₈B₂₄ (at. pct) coatings are interesting to protect mild steels such as the API 5L X80 against corrosion in chloride-rich environments.

     

Two-wave-plate compensator method for full-field retardation measurements

The two-wave-plate compensator (TWC) method is expanded for full-field retardation measurements by use of a polarization microscope. The sample image is projected onto a CCD camera connected to a computer, allowing the retardation to be measured at all pixels. The retardation accuracy of this implementation of the TWC is evaluated to be 0.06 nm. The method is applied to polarization-maintaining fibers and long-period fiber gratings. The measured retardation is in good agreement with the crossed-polarizer images of the fibers. The method achieves a spatial resolution of 0.45 microm and a retardation resolution of 0.07 nm. The full-field TWC method can thus be a useful tool for characterizing and monitoring the fabrication of optical devices.     

Optical characterization of an unknown single layer: Institut Fresnel contribution to the Optical Interference Coatings 2004 Topical Meeting Measurement Problem

We present the characterizations performed at the Institut Fresnel for the Measurement Problem of the Optical Interference Coatings 2004 Topical Meeting. A single layer coated on a fused-silica substrate of unknown composition and parameters is analyzed in terms of optogeometrical parameters, uniformity, and scattering. We determine the refractive index and the average thickness of the coating, then provide the localized determination of the thickness with a 2 mm spatial resolution. Topography measurements include atomic force microscopy and angle-resolved scattering measurements. These results are completed thanks to a Taylor Hobson noncontact 3D surface profiler.     

Ellipsometry of reflected and scattered fields for the analysis of substrate optical quality

Specular ellipsometry is a well-known and efficient technique to characterize surfaces and coatings. This technique has been extended to the measurement of scattered light. We present an experimental setup, using a polarization modulator, which permits us to characterize transition layers and roughness without a calibration procedure. Experimental results are presented concerning transition layers for damage threshold applications and for rough surfaces or bulks.     

Acellular comet assay: a tool for assessing variables influencing the alkaline comet assay

In this study, an acellular modification to the alkaline comet assay to further evaluate key variables within the assay that may influence the outcome of genotoxicity studies is described. This acellular comet assay can detect differences of 0.2 Gy of (60)Co gamma-ray radiation between 0 and 1 Gy and differences of 1 Gy between 0 and 8 Gy; thus, this assay is applicable for a wide range of DNA damage levels. It is also shown that DNA damage from different radiation energies was not significantly different from (60)Co gamma-ray. This assay displayed a statistical increase in DNA damage due to uncontrolled exposure to natural light; however, the slope of the dose-response curve for light-exposed samples was similar to that for samples protected from light. A comparison of the alkaline comet assay with the acellular comet assay allowed for the intrinsic repair capacity of the alkaline comet assay to be quantified.