Effects of urbanization on host-pathogen interactions, using Yersinia in house sparrows as a model

Urbanization strongly affects biodiversity, altering natural communities and often leading to a reduced species richness. Yet, despite its increasingly recognized importance, how urbanization impacts on the health of individual animals, wildlife populations and on disease ecology remains poorly understood. To test whether, and how, urbanization-driven ecosystem alterations influence pathogen dynamics and avian health, we use house sparrows (Passer domesticus) and Yersinia spp. (pathogenic for passerines) as a case study. Sparrows are granivorous urban exploiters, whose western European populations have declined over the past decades, especially in highly urbanized areas. We sampled 329 house sparrows originating from 36 populations along an urbanization gradient across Flanders (Belgium), and used isolation combined with 'matrix-assisted laser desorption ionization-time of flight mass spectrometry' (MALDI-TOF MS) and PCR methods for detecting the presence of different Yersinia species. Yersinia spp. were recovered from 57.43% of the sampled house sparrows, of which 4.06%, 53.30% and 69.54% were identified as Y. pseudotuberculosis, Y. enterocolitica and other Yersinia species, respectively. Presence of Yersinia was related to the degree of urbanization, average daily temperatures and the community of granivorous birds present at sparrow capture locations. Body condition of suburban house sparrows was found to be higher compared to urban and rural house sparrows, but no relationships between sparrows' body condition and presence of Yersinia spp. were found. We conclude that two determinants of pathogen infection dynamics, body condition and pathogen occurrence, vary along an urbanization gradient, potentially mediating the impact of urbanization on avian health

Ubiquitous LibGuides: Variations in Presence, Production, Application, and Convention

The LibGuides platform, a content management system (CMS) from Springshare, has become an integral part of the online presence for many academic libraries. Neither Springshare nor other recent studies have provided an in-depth look at the evolving nature of LibGuides adoption, production and application across university and college categories. This study compared the prevalence and production of LibGuides to other forms of library guides at 799 academic libraries throughout the United States. LibGuides naming conventions were recorded and compared. The use of LibGuides CMS software to create library websites was also documented. This study found that there are clear differences in LibGuides adoption and production across various types of institutions. LibGuides naming conventions were fairly consistent across all types of institutions. Institutions using LibGuides software produced substantially more library guides than institutions without this software. A small but significant portion of all non-R1 libraries in this study are now utilizing LibGuides software to create the majority of their library websites

Low prevalence of human enteropathogenic Yersinia spp. in brown rats (Rattus norvegicus) in Flanders

Brown rats (Rattus norvegicus) have been identified as potential carriers of Yersinia enterocolitica and Y. pseudotuberculosis, the etiological agents of yersiniosis, the third most reported bacterial zoonosis in Europe. Enteropathogenic Yersinia spp. are most often isolated from rats during yersiniosis cases in animals and humans, and from rats inhabiting farms and slaughterhouses. Information is however lacking regarding the extent to which rats act as carriers of these Yersinia spp.. In 2013, 1088 brown rats across Flanders, Belgium, were tested for the presence of Yersinia species by isolation method. Identification was performed using MALDI-TOF MS, PCR on chromosomal-and plasmid-borne virulence genes, biotyping and serotyping. Yersinia spp. were isolated from 38.4% of the rats. Of these, 53.4% were designated Y. enterocolitica, 0.7% Y. pseudotuberculosis and 49.0% other Yersinia species. Two Y. enterocolitica possessing the virF-, ail- and ystA-gene were isolated. Additionally, the ystB-gene was identified in 94.1% of the other Y. enterocolitica isolates, suggestive for biotype 1A. Three of these latter isolates simultaneously possessed the ail-virulence gene. Significantly more Y. enterocolitica were isolated during winter and spring compared to summer. Based on our findings we can conclude that brown rats are frequent carriers for various Yersinia spp., including Y. pseudotuberculosis and (human pathogenic) Y. enterocolitica which are more often isolated during winter and spring

Application of a new approach methodology (NAM)-based strategy for genotoxicity assessment of data-poor compounds

The conventional battery for genotoxicity testing is not well suited to assessing the large number of chemicals needing evaluation. Traditional in vitro tests lack throughput, provide little mechanistic information, and have poor specificity in predicting in vivo genotoxicity. New Approach Methodologies (NAMs) aim to accelerate the pace of hazard assessment and reduce reliance on in vivo tests that are time-consuming and resource-intensive. As such, high-throughput transcriptomic and flow cytometry-based assays have been developed for modernized in vitro genotoxicity assessment. This includes: the TGx-DDI transcriptomic biomarker (i.e., 64-gene expression signature to identify DNA damage-inducing (DDI) substances), the MicroFlow® assay (i.e., a flow cytometry-based micronucleus (MN) test), and the MultiFlow® assay (i.e., a multiplexed flow cytometry-based reporter assay that yields mode of action (MoA) information). The objective of this study was to investigate the utility of the TGx-DDI transcriptomic biomarker, multiplexed with the MicroFlow® and MultiFlow® assays, as an integrated NAM-based testing strategy for screening data-poor compounds prioritized by Health Canada’s New Substances Assessment and Control Bureau. Human lymphoblastoid TK6 cells were exposed to 3 control and 10 data-poor substances, using a 6-point concentration range. Gene expression profiling was conducted using the targeted TempO-Seq™ assay, and the TGx-DDI classifier was applied to the dataset. Classifications were compared with those based on the MicroFlow® and MultiFlow® assays. Benchmark Concentration (BMC) modeling was used for potency ranking. The results of the integrated hazard calls indicate that five of the data-poor compounds were genotoxic in vitro, causing DNA damage via a clastogenic MoA, and one via a pan-genotoxic MoA. Two compounds were likely irrelevant positives in the MN test; two are considered possibly genotoxic causing DNA damage via an ambiguous MoA. BMC modeling revealed nearly identical potency rankings for each assay. This ranking was maintained when all endpoint BMCs were converted into a single score using the Toxicological Prioritization (ToxPi) approach. Overall, this study contributes to the establishment of a modernized approach for effective genotoxicity assessment and chemical prioritization for further regulatory scrutiny. We conclude that the integration of TGx-DDI, MicroFlow®, and MultiFlow® endpoints is an effective NAM-based strategy for genotoxicity assessment of data-poor compounds

Human Plasmodium knowlesi Infection Detected by Rapid Diagnostic Tests for Malaria

We describe a PCR-confirmed case of Plasmodium knowlesi infection with a high parasitemia level and clinical signs of severe malaria in a migrant worker from Malaysian Borneo in the Netherlands. Investigations showed that commercially available rapid antigen tests for detection of human Plasmodium infections can detect P. knowlesi infections in humans

Altered splicing of the BIN1 muscle-specific exon in humans and dogs with highly progressive centronuclear myopathy

Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies

“THE FASHIONS OF THE CURRENT SEASON”: RECENT CRITICAL WORK ON VICTORIAN SENSATION FICTION

This paper was accepted for publication in the journal Victorian Literature and Culture and the definitive published version is available at https://doi.org/10.1017/S106015031600072

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants