89 research outputs found

    Whole-Genome Sequencing-Based Characterization of 100 Listeria monocytogenes Isolates Collected from Food Processing Environments over a Four-Year Period

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    Listeria monocytogenes is frequently found in foods and processing facilities, where it can persist, creating concerns for the food industry. Its ability to survive under a wide range of environmental conditions enhances the potential for cross-contamination of the final food products, leading to possible outbreaks of listeriosis. In this study, whole-genome sequencing (WGS) was applied as a tool to characterize and track 100 L. monocytogenes isolates collected from three food processing environments. These WGS data from environmental and food isolates were analyzed to (i) assess the genomic diversity of L. monocytogenes, (ii) identify possible source(s) of contamination, cross-contamination routes, and persistence, (iii) detect absence/presence of antimicrobial resistance-encoding genes, (iv) assess virulence genotypes, and (v) explore in vivo pathogenicity of selected L. monocytogenes isolates carrying different virulence genotypes. The predominant L. monocytogenes sublineages (SLs) identified were SL101 (21%), SL9 (17%), SL121 (12%), and SL5 (12%). Benzalkonium chloride (BC) tolerance-encoding genes were found in 62% of these isolates, a value that increased to 73% among putative persistent subgroups. The most prevalent gene was emrC followed by bcrABC, qacH-Tn6188, and qacC. The L. monocytogenes major virulence factor inlA was truncated in 31% of the isolates, and only one environmental isolate (L. monocytogenes CFS086) harbored all major virulence factors, including Listeria pathogenicity island 4 (LIPI-4), which has been shown to confer hypervirulence. A zebrafish embryo infection model showed a low (3%) embryo survival rate for all putatively hypervirulent L. monocytogenes isolates assayed. Higher embryo survival rates were observed following infection with unknown virulence potential (20%) and putatively hypovirulent (53 to 83%) L. monocytogenes isolates showing predicted pathogenic phenotypes inferred from virulence genotypes

    Early participation in a prenatal food supplementation program ameliorates the negative association of food insecurity with quality of maternal-infant interaction.

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    Food insecurity is detrimental to child development, yet little is known about the combined influence of food insecurity and nutritional interventions on child development in low-income countries. We proposed that women assigned to an early invitation time to start a prenatal food supplementation program could reduce the negative influence of food insecurity on maternal-infant interaction. A cohort of 180 mother-infant dyads were studied (born between May and October 2003) from among 3267 in the randomized controlled trial Maternal Infant Nutritional Interventions Matlab, which was conducted in Matlab, Bangladesh. At 8 wk gestation, women were randomly assigned an invitation time to start receiving food supplements (2.5 MJ/d; 6 d/wk) either early (~9 wk gestation; early-invitation group) or at the usual start time (~20 wk gestation; usual-invitation group) for the government program. Maternal-infant interaction was observed in homes with the use of the Nursing Child Assessment Satellite Training Feeding Scale, and food-insecurity status was obtained from questionnaires completed when infants were 3.4-4.0 mo old. By using a general linear model for maternal-infant interaction, we found a significant interaction (P = 0.012) between invitation time to start a prenatal food supplementation program and food insecurity. Those in the usual-invitation group with higher food insecurity scores (i.e., more food insecure) had a lower quality of maternal-infant interaction, but this relationship was ameliorated among those in the early-invitation group. Food insecurity limits the ability of mothers and infants to interact well, but an early invitation time to start a prenatal food supplementation program can support mother-infant interaction among those who are food insecure

    Evolutionary Patterning: A Novel Approach to the Identification of Potential Drug Target Sites in Plasmodium falciparum

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    Malaria continues to be the most lethal protozoan disease of humans. Drug development programs exhibit a high attrition rate and parasite resistance to chemotherapeutic drugs exacerbates the problem. Strategies that limit the development of resistance and minimize host side-effects are therefore of major importance. In this study, a novel approach, termed evolutionary patterning (EP), was used to identify suitable drug target sites that would minimize the emergence of parasite resistance. EP uses the ratio of non-synonymous to synonymous substitutions (ω) to assess the patterns of evolutionary change at individual codons in a gene and to identify codons under the most intense purifying selection (ω≤0.1). The extreme evolutionary pressure to maintain these residues implies that resistance mutations are highly unlikely to develop, which makes them attractive chemotherapeutic targets. Method validation included a demonstration that none of the residues providing pyrimethamine resistance in the Plasmodium falciparum dihydrofolate reductase enzyme were under extreme purifying selection. To illustrate the EP approach, the putative P. falciparum glycerol kinase (PfGK) was used as an example. The gene was cloned and the recombinant protein was active in vitro, verifying the database annotation. Parasite and human GK gene sequences were analyzed separately as part of protozoan and metazoan clades, respectively, and key differences in the evolutionary patterns of the two molecules were identified. Potential drug target sites containing residues under extreme evolutionary constraints were selected. Structural modeling was used to evaluate the functional importance and drug accessibility of these sites, which narrowed down the number of candidates. The strategy of evolutionary patterning and refinement with structural modeling addresses the problem of targeting sites to minimize the development of drug resistance. This represents a significant advance for drug discovery programs in malaria and other infectious diseases

    The top 10 research priorities in cystic fibrosis developed by a partnership between people with CF and health care providers

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    There remain many treatment uncertainties in cystic fibrosis (CF). With limited resources, research should focus on questions which are most important to the CF community. We conducted a James Lind Alliance Priority Setting Partnership in CF. Research questions were elicited and then prioritised in successive surveys. A workshop agreed the final Top 10. Online methods avoided cross infection and widened participation. The elicitation survey had 482 respondents (1080 questions) and prioritisation survey 677 respondents. Participants were drawn equally from the patient and clinical communities globally. We have achieved a consensus on ten research priorities which will be attractive to funders

    Quantifying ionospheric effects on time-domain astrophysics with the Murchison Widefield Array

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    © 2015 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society. Refraction and diffraction of incoming radio waves by the ionosphere induce time variability in the angular positions, peak amplitudes and shapes of radio sources, potentially complicating the automated cross-matching and identification of transient and variable radio sources. In this work, we empirically assess the effects of the ionosphere on data taken by the Murchison Widefield Array (MWA) radio telescope. We directly examine 51 h of data observed over 10 nights under quiet geomagnetic conditions (global storm index Kp < 2), analysing the behaviour of short-time-scale angular position and peak flux density variations of around ten thousand unresolved sources. We find that while much of the variation in angular position can be attributed to ionospheric refraction, the characteristic displacements (10-20 arcsec) at 154 MHz are small enough that search radii of 1-2 arcmin should be sufficient for crossmatching under typical conditions. By examining bulk trends in amplitude variability, we place upper limits on the modulation index associated with ionospheric scintillation of 1-3 per cent for the various nights. For sources fainter than ~1 Jy, this variation is below the image noise at typical MWA sensitivities. Our results demonstrate that the ionosphere is not a significant impediment to the goals of time-domain science with the MWA at 154 MHz

    Serendipitous discovery of a dying Giant Radio Galaxy associated with NGC 1534, using the murchison widefield array

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    Recent observations with the Murchison Widefield Array at 185 MHz have serendipitously unveiled a heretofore unknown giant and relatively nearby (z=0.0178) radio galaxy associated with NGC 1534. The diffuse emission presented here is the first indication that NGC 1534 is one of a rare class of objects (along with NGC 5128 and NGC 612) in which a galaxy with a prominent dust lane hosts radio emission on scales of ~700 kpc. We present details of the radio emission along with a detailed comparison with other radio galaxies with discs. NGC 1534 is the lowest surface brightness radio galaxy known with an estimated scaled 1.4-GHz surface brightness of just 0.2 mJy arcmin-2. The radio lobes have one of the steepest spectral indices yet observed: α = -2.1 ± 0.1, and the core to lobe luminosity ratio is <0.1 per cent. We estimate the space density of this low brightness (dying) phase of radio galaxy evolution as 7 × 10-7 Mpc-3 and argue that normal AGN cannot spend more than 6 per cent of their lifetime in this phase if they all go through the same cycle

    Dynamic Emotional and Neural Responses to Music Depend on Performance Expression and Listener Experience

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    Apart from its natural relevance to cognition, music provides a window into the intimate relationships between production, perception, experience, and emotion. Here, emotional responses and neural activity were observed as they evolved together with stimulus parameters over several minutes. Participants listened to a skilled music performance that included the natural fluctuations in timing and sound intensity that musicians use to evoke emotional responses. A mechanical performance of the same piece served as a control. Before and after fMRI scanning, participants reported real-time emotional responses on a 2-dimensional rating scale (arousal and valence) as they listened to each performance. During fMRI scanning, participants listened without reporting emotional responses. Limbic and paralimbic brain areas responded to the expressive dynamics of human music performance, and both emotion and reward related activations during music listening were dependent upon musical training. Moreover, dynamic changes in timing predicted ratings of emotional arousal, as well as real-time changes in neural activity. BOLD signal changes correlated with expressive timing fluctuations in cortical and subcortical motor areas consistent with pulse perception, and in a network consistent with the human mirror neuron system. These findings show that expressive music performance evokes emotion and reward related neural activations, and that music's affective impact on the brains of listeners is altered by musical training. Our observations are consistent with the idea that music performance evokes an emotional response through a form of empathy that is based, at least in part, on the perception of movement and on violations of pulse-based temporal expectancies

    Low frequency observations of linearly polarized structures in the interstellar medium near the south Galactic pole

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    This is an author-created, un-copyedited version of an article published in The Astrophysical Journal. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at https://doi.org/10.3847/0004-637X/830/1/38We present deep polarimetric observations at 154 MHz with the Murchison Widefield Array (MWA), covering 625 deg^2 centered on RA=0 h, Dec=-27 deg. The sensitivity available in our deep observations allows an in-band, frequency-dependent analysis of polarized structure for the first time at long wavelengths. Our analysis suggests that the polarized structures are dominated by intrinsic emission but may also have a foreground Faraday screen component. At these wavelengths, the compactness of the MWA baseline distribution provides excellent snapshot sensitivity to large-scale structure. The observations are sensitive to diffuse polarized emission at ~54' resolution with a sensitivity of 5.9 mJy beam^-1 and compact polarized sources at ~2.4' resolution with a sensitivity of 2.3 mJy beam^-1 for a subset (400 deg^2) of this field. The sensitivity allows the effect of ionospheric Faraday rotation to be spatially and temporally measured directly from the diffuse polarized background. Our observations reveal large-scale structures (~1 deg - 8 deg in extent) in linear polarization clearly detectable in ~2 minute snapshots, which would remain undetectable by interferometers with minimum baseline lengths >110 m at 154 MHz. The brightness temperature of these structures is on average 4 K in polarized intensity, peaking at 11 K. Rotation measure synthesis reveals that the structures have Faraday depths ranging from -2 rad m^-2 to 10 rad m^-2 with a large fraction peaking at ~+1 rad m^-2. We estimate a distance of 51+/-20 pc to the polarized emission based on measurements of the in-field pulsar J2330-2005. We detect four extragalactic linearly polarized point sources within the field in our compact source survey. Based on the known polarized source population at 1.4 GHz and non-detections at 154 MHz, we estimate an upper limit on the depolarization ratio of 0.08 from 1.4 GHz to 154 MHz.Peer reviewedFinal Accepted Versio
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