The Canadian Cooperative Wildlife Health Centre and Surveillance of Wild Animal Diseases in Canada, Volume 38, May 1997

The Canadian Cooperative Wildlife Health Centre (CCWHC) was established in 1992 as an organization among Canada\u27s 4 veterinary colleges, with a mandate to apply veterinary medicine to wildlife management and conservation in Canada. A major function of the CCWHC is nation-wide surveillance of wild animal diseases. Disease surveillance is conceived as consisting of 4 different activities: detection, diagnosis, information management, and use of information. In the CCWHC surveillance program, detection of disease is carried out by a wide range of professional and avocational field personnel, and much effort is expended to stimulate and support this activity. Diagnosis is done by personnel of provincial and federal veterinary laboratories and the CCWHC. Information management is achieved through a national database of wildlife disease incidents developed and maintained by the CCWHC. Use of information is enabled through established channels for distribution of information derived from the surveillance program to persons responsible for wildlife programs and policies, and to the public. There has been a high demand for the services of the CCWHC since its establishment. The CCWHC responds to approximately 2000 requests for information annually, distributes its newsletter to over 1700 recipients, examines approximately 1200 wild animal submissions each year, and has accumulated records of over 5000 disease incidents in its database. Technical information from the CCWHC has benefited federal, provincial/territorial, and non-government wildlife agencies; endangered species recovery programs; federal and provincial veterinary services; and federal and provincial public health programs

The Canadian Cooperative Wildlife Health Centre and Surveillance of Wild Animal Diseases in Canada, Volume 38, May 1997

The Canadian Cooperative Wildlife Health Centre (CCWHC) was established in 1992 as an organization among Canada\u27s 4 veterinary colleges, with a mandate to apply veterinary medicine to wildlife management and conservation in Canada. A major function of the CCWHC is nation-wide surveillance of wild animal diseases. Disease surveillance is conceived as consisting of 4 different activities: detection, diagnosis, information management, and use of information. In the CCWHC surveillance program, detection of disease is carried out by a wide range of professional and avocational field personnel, and much effort is expended to stimulate and support this activity. Diagnosis is done by personnel of provincial and federal veterinary laboratories and the CCWHC. Information management is achieved through a national database of wildlife disease incidents developed and maintained by the CCWHC. Use of information is enabled through established channels for distribution of information derived from the surveillance program to persons responsible for wildlife programs and policies, and to the public. There has been a high demand for the services of the CCWHC since its establishment. The CCWHC responds to approximately 2000 requests for information annually, distributes its newsletter to over 1700 recipients, examines approximately 1200 wild animal submissions each year, and has accumulated records of over 5000 disease incidents in its database. Technical information from the CCWHC has benefited federal, provincial/territorial, and non-government wildlife agencies; endangered species recovery programs; federal and provincial veterinary services; and federal and provincial public health programs

Genome-Wide Analysis of the Response of Dickeya dadantii 3937 to Plant Antimicrobial Peptides

Antimicrobial peptides constitute an important factor in the defense of plants against pathogens, and bacterial resistance to these peptides have previously been shown to be an important virulence factor in Dickeya dadantii, the causal agent of soft-rot disease of vegetables. In order to understand the bacterial response to antimicrobial pep- tides, a transcriptional microarray analysis was performed upon treatment with sub-lethal concentration of thionins, a widespread plant peptide. In all, 36 genes were found to be overexpressed, and were classified according to their deduced function as i) transcriptional regulators, ii) transport, and iii) modification of the bacterial membrane. One gene encoding a uricase was found to be repressed. The majority of these genes are known to be under the control of the PhoP/PhoQ system. Five genes representing the different functions induced were selected for further analysis. The results obtained indicate that the presence of antimicrobial peptides induces a complex response which includes peptide-specific elements and general stress-response elements contributing differentially to the virulence in different hosts

Review of offshore CO2 storage monitoring: operational and research experiences of meeting regulatory and technical requirements

Legislation for offshore storage has been developing over the last decade or so and is currently most developed in Europe. Although the large-scale operating sites in Europe were started prior to the regulations coming into force, any planned sites will need to meet these regulatory requirements. Our review of monitoring experiences from both the operating sites and research at experimental injection sites and in areas of natural CO2 seepage suggest that broadly, the technical and regulatory challenges of offshore monitoring can be met. A full report reviewing offshore monitoring including tool capabilities, practicalities and costs is available from IEAGHG (released Q1 2016)

Perspectives of community pharmacy staff on commonly encountered skin conditions and the key challenges towards enhancing their role in dermatology

This research letter discusses the perspectives of community pharmacy staff on commonly encountered skin conditions and the key challenges towards enhancing their role in this area. A mixed methods online survey was created, and a total of 174 community pharmacy staff completed the survey. The results highlight the range of conditions currently encountered in community pharmacy and the breadth of challenges facing community pharmacy staff, in particular challenges surrounding providing a differential diagnosis. Community pharmacies are an integral part of the NHS and have a key role in managing skin conditions; however, in order to optimise this role, the perspectives of staff discussed in this letter need to be further explored and addressed

Draft genome sequences of four Dickeya dianthicola and four Dickeya solani strains

Dickeya dianthicola and "Dickeya solani" are currently the dominant bacterial pathogens of potatoes in Europe. Here, we present the draft genome sequences of four strains of each pathogen

Genotype-phenotype characterisation of long survivors with motor neuron disease in Scotland

Background: We investigated the phenotypes and genotypes of a cohort of ‘long-surviving’ individuals with motor neuron disease (MND) to identify potential targets for prognostication. Methods: Patients were recruited via the Clinical Audit Research and Evaluation for MND (CARE-MND) platform, which hosts the Scottish MND Register. Long survival was defined as > 8 years from diagnosis. 11 phenotypic variables were analysed. Whole genome sequencing (WGS) was performed and variants within 49 MND-associated genes examined. Each individual was screened for C9orf72 repeat expansions. Data from ancestry-matched Scottish populations (the Lothian Birth Cohorts) were used as controls. Results: 58 long survivors were identified. Median survival from diagnosis was 15.5 years. Long survivors were significantly younger at onset and diagnosis than incident patients and had a significantly longer diagnostic delay. 42% had the MND subtype of primary lateral sclerosis (PLS). WGS was performed in 46 individuals: 14 (30.4%) had a potentially pathogenic variant. 4 carried the known SOD1 p.(Ile114Thr) variant. Significant variants in FIG4, hnRNPA2B1, SETX, SQSTM1, TAF15, and VAPB were detected. 2 individuals had a variant in the SPAST gene suggesting phenotypic overlap with hereditary spastic paraplegia (HSP). No long survivors had pathogenic C9orf72 repeat expansions. Conclusions: Long survivors are characterised by younger age at onset, increased prevalence of PLS and longer diagnostic delay. Genetic analysis in this cohort has improved our understanding of the phenotypes associated with the SOD1 variant p.(Ile114Thr). Our findings confirm that pathogenic expansion of C9orf72 is likely a poor prognostic marker. Genetic screening using targeted MND and/or HSP panels should be considered in those with long survival, or early-onset slowly progressive disease, to improve diagnostic accuracy and aid prognostication

High-Throughput Virtual Screening and Validation of a SARS-CoV-2 Main Protease Noncovalent Inhibitor

Despite the recent availability of vaccines against the acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the search for inhibitory therapeutic agents has assumed importance especially in the context of emerging new viral variants. In this paper, we describe the discovery of a novel noncovalent small-molecule inhibitor, MCULE-5948770040, that binds to and inhibits the SARS-Cov-2 main protease (Mpro) by employing a scalable high-throughput virtual screening (HTVS) framework and a targeted compound library of over 6.5 million molecules that could be readily ordered and purchased. Our HTVS framework leverages the U.S. supercomputing infrastructure achieving nearly 91% resource utilization and nearly 126 million docking calculations per hour. Downstream biochemical assays validate this Mpro inhibitor with an inhibition constant (Ki) of 2.9 μM (95% CI 2.2, 4.0). Furthermore, using room-temperature X-ray crystallography, we show that MCULE-5948770040 binds to a cleft in the primary binding site of Mpro forming stable hydrogen bond and hydrophobic interactions. We then used multiple μs-time scale molecular dynamics (MD) simulations and machine learning (ML) techniques to elucidate how the bound ligand alters the conformational states accessed by Mpro, involving motions both proximal and distal to the binding site. Together, our results demonstrate how MCULE-5948770040 inhibits Mpro and offers a springboard for further therapeutic design

Genetic characterization of the HrpL regulon of the fire blight pathogen Erwinia amylovora reveals novel virulence factors

The bacterial pathogen Erwinia amylovora is the causal agent of fire blight, an economically significant disease of apple and pear. Disease initiation by E. amylovora requires the translocation of effector proteins into host cells via the hypersensitive response and pathogenicity (hrp) type III secretion system (T3SS). The alternative sigma factor HrpL positively regulates the transcription of structural and translocated components of the T3SS via hrp promoter elements. To characterize genome-wide HrpL-dependent gene expression in E. amylovora Ea1189, wild-type and Ea1189ΔhrpL strains were cultured in hrp-inducing minimal medium, and total RNA was compared using a custom microarray designed to represent the annotated genes of E. amylovora ATCC 49946. The results revealed 24 genes differentially regulated in Ea1189ΔhrpL relative to Ea1189 with fold-change expression ratios greater than 1.5; of these, 19 genes exhibited decreased transcript abundance and five genes showed increased transcript abundance relative to Ea1189. To expand our understanding of the HrpL regulon and to elucidate direct versus indirect HrpL-mediated effects on gene expression, the genome of E. amylovora ATCC 49946 was examined insilico using a hidden Markov model assembled from known Erwinia spp. hrp promoters. This technique identified 15 putative type III novel hrp promoters, seven of which were validated with quantitative polymerase chain reaction based on expression analyses. It was found that HrpL-regulated genes encode all known components of the hrp T3SS, as well as five putative type III effectors. Eight genes displayed apparent indirect HrpL regulation, suggesting that the HrpL regulon is connected to downstream signalling networks. The construction of deletion mutants of three novel HrpL-regulated genes resulted in the identification of additional virulence factors as well as mutants displaying abnormal motility and biofilm phenotypes