Selective Vulnerability of the Cochlear Basal Turn to Acrylonitrile and Noise

Exposure to acrylonitrile, a high-production industrial chemical, can promote noise-induced hearing loss (NIHL) in the rat even though this agent does not itself produce permanent hearing loss. The mechanism by which acrylonitrile promotes NIHL includes oxidative stress as antioxidant drugs can partially protect the cochlea from acrylonitrile + noise. Acrylonitrile depletes glutathione levels while noise can increase the formation of reactive oxygen species. It was previously noted that the high-frequency or basal turn of the cochlea was particularly vulnerable to the combined effects of acrylonitrile and noise when the octave band noise (OBN) was centered at 8 kHz. Normally, such a noise would be expected to yield damage at a more apical region of the cochlea. The present study was designed to determine whether the basal cochlea is selectively sensitive to acrylonitrile or whether, by adjusting the frequency of the noise band, it would be possible to control the region of the auditory impairment. Rats were exposed to one of three different OBNs centered at different frequencies (4 kHz, 110 dB and 8 or 16 kHz at 97 dB) for 5 days, with and without administration of acrylonitrile (50 mg/kg/day). The noise was set to cause limited NIHL by itself. Auditory function was monitored by recording distortion products, by compound action potentials, and by performing cochlear histology. While the ACN-only and noise-only exposures induced no or little permanent auditory loss, the three exposures to acrylonitrile + noise produced similar auditory and cochlear impairments above 16 kHz, despite the fact that the noise exposures covered 2 octaves. These observations show that the basal cochlea is much more sensitive to acrylonitrile + noise than the apical partition. They provide an initial basis for distinguishing the pattern of cochlear injury that results from noise exposure from that which occurs due to the combined effects of noise and a chemical contaminant

Unpacking distinction within mobility : social prestige and international students

Author thanks the Social Sciences and Humanities Research Council of Canada (SSHRC) for their funding on this projecThis paper investigates the complex ways in which young people engage in social distinction within international mobility. The study offers novel conceptual and empirical insights by examining how distinction and social advantage is reproduced through short‐term student mobility from the Global North to the Global South. In doing so, it elucidates the iterative process of distinction‐making within mobility and argues that young mobile people negotiate a tension between different forms of distinction. Specifically, it unpacks and conceptualises distinction into dual categories—collective and individual—and suggests that students alternate and waver between these categories in order to both validate and elevate their position within a mobility hierarchy. The paper also considers how particular places are viewed as more distinctive and affording greater gains in cultural and symbolic capital. It concludes with future interrogations and ways forward for research on international mobility and distinction.PostprintPeer reviewe

Etablierung einer Methode zur Phänotypisierung der Schwarzfäule (Guignardia bidwellii) resistenz in der Weinrebe (Vitis spec.)

Development of a method for phenotyping Black Rot (Guignardia bidwellii) resistance on grapevine (Vitis spec.)ZusammenfassungDer Erreger der Schwarzfäule Guignardia bidwellii wurde im 19. Jahrhundert aus Nordamerika nach Europa eingeschleppt. Seit 2002 wird der Ascomycet vermehrt in deutschen Weinanbaugebieten beobachtet und führt gebietsweise zu erheblicher Ertragsminderung. Dies gibt Anlass, in Zukunft Schwarzfäule resistente Reben zu züchten. Für die Züchtung ist eine Methode erforderlich, um eine große Anzahl an Reben schnell und zuverlässig bezüglich ihrer Anfälligkeit gegen die Schwarzfäule zu charakterisieren. Vorgestellt wird ein Verfahren der Phänotypisierung der Resistenz in der Rebe, sowie die Durchführung der Bonitur und deren Ergebnisse. Die Bonituren sind darauf ausgerichtet, Daten zu erheben, die für genetische Analysen (hier QTL) verwendbar sind. Letztendlich werden molekulare Marker entwickelt, die eng mit dem Merkmal Schwarzfäule Resistenz gekoppelt sind und daher in der Züchtung zur Frühselektion von Reben verwendet werden können. Stichwörter: Schwarzfäule, Weinrebe, ZüchtungAbstractBlack Rot of grapevine is caused by the Ascomycet Guignardia bidwellii. The pathogen was introduced from North America to Europe in the 19th century. Since 2002 increased effects of the disease have been noticed, causing significant yield losses in the region of Mosel and infections in all German wine-growing regions. For that reason, it is important to breed Black Rot resistant grapevine cultivars. A method has been developed to characterize lots of vines in a fast and reliable way concerning their susceptibility. First data have been collected and can be used for genetic analysis (here QTL). The aim of the project is to develop a molecular marker correlating with Black Rot resistance which can be used to select juvenile plants and therefore supporting the breeding of resistant cultivars.Keywords: Black Rot, Grapevine, Breedin

Effects of carbon monoxide on cochlear electrophysiology and blood flow

The belief that the cochlea is particularly vulnerable to a reduction in oxygen availability comes predominantly from studies reporting the disruption of electrophysiological measures, such as the compound action potential, endocochlear potential, inner hair cell intracellular potentials or afferent nerve fiber responses by asphyxiation. Because hypoxia has frequently been suggested as an underlying mechanism by which many ototoxic agents produce injury, and because such agents are not likely to completely disrupt oxygen delivery, we investigated the effects of graded hypoxia (using doses of carbon monoxide) on cochlear blood flow, the compound action potential (CAP) and the cochlear microphonic (CM). High doses of carbon monoxide injected intra-peritoneally yielded reversible loss of the CAP sensitivity for high frequency tone bursts, the extent of which was dose dependent. The loss was observed first at the highest frequency tested (50 kHz) and as carboxyhemoglobin levels increased, contiguous lower frequencies were influenced. Recovery progressed from low to high frequencies as carboxyhemoglobin levels declined. Carbon monoxide administration also produced a dose dependent elevation in the cochlear blood flow measured by a laser Doppler flow monitor. The data suggest that carbon monoxide administration disrupts cochlear function only under extremely severe exposure conditions. An elevation in cochlear blood flow may well serve as a protective mechanism which maintains cochlear function in the face of declining blood oxygen carrying capacity and delivery. While the site of action of carbon monoxide in the cochlea is uncertain, the data clearly indicate that elements involved in the generation of the CAP for high frequency tones are particularly vulnerable. This suggests that such elements may have different metabolic requirements from other lower frequency regions of the cochlea and/or that oxygen delivery (blood circulation) differs in the basal portion of the cochlea.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26857/1/0000422.pd

Current status of arsenic contamination in drinkingwater and treatment practice in some rural areas of West Bengal, India

The aim of the present investigation was to draw the current scenario of arsenic (As) contamination in drinking water of community tube well and drinking water treated by tube wells installed with different adsorbent media-based treatment plants in districts Nadia, Hooghly and North 24-Parganas districts, West Bengal, India. As removal efficiencies of different treatment plants varied from 23 to 71%, which is largely governed by adsorption capacity of adsorbent and influencing environmental factors. Though investigated treatment plants removed substantial amount of As from tube well water, high As concentration in treated drinking water was retained after passing through the treatment plants. This high level of As concentration in tube well water and retention of high As concentration in treated drinking water were severe for the consumers which therefore, indicating the improvement of removal efficiency of treatment plant by meticulously considering favorable influencing factors or/and application of other high capacity treatment alternatives to adsorb the excess As retained in drinking water and regular monitoring of As concentration in the treated drinking water are indispensable

WaSH CQI: Applying continuous quality improvement methods to water service delivery in four districts of rural northern Ghana

Continuous, safely managed water is critical to health and development, but rural service delivery faces complex challenges in low- and middle-income countries (LMICs). We report the first application of continuous quality improvement (CQI) methods to improve the microbial quality of household water for consumption (HWC) and the functionality of water sources in four rural districts of northern Ghana. We further report on the impacts of interventions developed through these methods. A local CQI team was formed and trained in CQI methods. Baseline data were collected and analyzed to identify determinants of service delivery problems and microbial safety. The CQI team randomized communities, developed an improvement package, iteratively piloted it in intervention communities, and used uptake survey data to refine the package. The final improvement package comprised safe water storage containers, refresher training for community WaSH committees and replacement of missing maintenance tools. This package significantly reduced contamination of HWC (p<0.01), and significant reduction in contamination persisted two years after implementation. Repair times in both intervention and control arms decreased relative to baseline (p<0.05), but differences between intervention and control arms were not significant at endline. Further work is needed to build on the gains in household water quality observed in this work, sustain and scale these improvements, and explore applications of CQI to other aspects of water supply and sanitation

RNA Biol

Non-coding (nc)RNAs are important players in most biological processes. Although small RNAs such as microRNAs and small interfering RNAs have emerged as exceptionally important regulators of gene expression, great numbers of larger ncRNAs have also been identified. Many of these are abundant and differentially expressed but their functions have in most cases not been elucidated. The social amoeba Dictyostelium discoideum contain the ncRNAs commonly found in eukaryotes. In addition, we previously reported the identification of two novel classes of 42-65 nt long stem-loop forming RNAs, Class I and Class II RNAs, with unknown function. In this study we have further characterized these abundant ncRNAs, which are down regulated during development. We have confirmed expression of 29 Class I RNAs and experimentally verified the formation of the computationally predicted short conserved stem structure. Furthermore, we have for the first time created knockout strains for several small ncRNA genes in D. discoideum and found that deletion of one of the Class I RNAs, DdR-21, results in aberrant development. In addition we have shown that this Class I RNA forms a complex with one or several proteins but do not appear to be associated with ribosomes or polysomes. In a pull down assay, several proteins interacting with DdR-21 were identified, one of these has two RNA recognition motifs (RRMs). The purified RRM containing protein was demonstrated to bind directly and specifically to DdR-21

Staphylococcus aureus RNAIII Binds to Two Distant Regions of coa mRNA to Arrest Translation and Promote mRNA Degradation

Staphylococcus aureus RNAIII is the intracellular effector of the quorum sensing system that temporally controls a large number of virulence factors including exoproteins and cell-wall-associated proteins. Staphylocoagulase is one major virulence factor, which promotes clotting of human plasma. Like the major cell surface protein A, the expression of staphylocoagulase is strongly repressed by the quorum sensing system at the post-exponential growth phase. Here we used a combination of approaches in vivo and in vitro to analyze the mechanism used by RNAIII to regulate the expression of staphylocoagulase. Our data show that RNAIII represses the synthesis of the protein through a direct binding with the mRNA. Structure mapping shows that two distant regions of RNAIII interact with coa mRNA and that the mRNA harbors a conserved signature as found in other RNAIII-target mRNAs. The resulting complex is composed of an imperfect duplex masking the Shine-Dalgarno sequence of coa mRNA and of a loop-loop interaction occurring downstream in the coding region. The imperfect duplex is sufficient to prevent the formation of the ribosomal initiation complex and to repress the expression of a reporter gene in vivo. In addition, the double-strand-specific endoribonuclease III cleaves the two regions of the mRNA bound to RNAIII that may contribute to the degradation of the repressed mRNA. This study validates another direct target of RNAIII that plays a role in virulence. It also illustrates the diversity of RNAIII-mRNA topologies and how these multiple RNAIII-mRNA interactions would mediate virulence regulation

PLoS Biol

Regulation of translation initiation is well appropriate to adapt cell growth in response to stress and environmental changes. Many bacterial mRNAs adopt structures in their 5' untranslated regions that modulate the accessibility of the 30S ribosomal subunit. Structured mRNAs interact with the 30S in a two-step process where the docking of a folded mRNA precedes an accommodation step. Here, we used a combination of experimental approaches in vitro (kinetic of mRNA unfolding and binding experiments to analyze mRNA-protein or mRNA-ribosome complexes, toeprinting assays to follow the formation of ribosomal initiation complexes) and in vivo (genetic) to monitor the action of ribosomal protein S1 on the initiation of structured and regulated mRNAs. We demonstrate that r-protein S1 endows the 30S with an RNA chaperone activity that is essential for the docking and the unfolding of structured mRNAs, and for the correct positioning of the initiation codon inside the decoding channel. The first three OB-fold domains of S1 retain all its activities (mRNA and 30S binding, RNA melting activity) on the 30S subunit. S1 is not required for all mRNAs and acts differently on mRNAs according to the signals present at their 5' ends. This work shows that S1 confers to the ribosome dynamic properties to initiate translation of a large set of mRNAs with diverse structural features