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Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly. Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly. Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.

Dit artikel verkent hoe we met behulp van het publieke waardeperspectief zicht kunnen krijgen op de kwaliteit van lokaal bestuur. Het publieke waardeperspectief beoordeelt de overheid niet op basis van algemene standaarden of benchmarks, maar via de oordelen van betrokken actoren. Deze benadering doet in potentie meer recht aan de unieke, lokale context van elke gemeente. Het publieke waardeperspectief wordt echter gecompliceerd door de veelheid aan verwachtingen die actoren hebben van bestuur en hun doorgaans negatieve vooringenomenheid ten opzichte van de overheid. Op basis van 71 interviews met verschillende actoren in zes gemeenten laten we zien hoe een publieke waardeperspectief op de vraag ‘wordt er hier goed bestuurd?’ uiteenlopende beelden oplevert, zelfs binnen gemeenten die door landelijke experts als succesvol worden gezien. Maar ook laten we zien welke verbindingen bestaan tussen deze beelden en hoe achter zuinige oordelen over het verleden optimistische ambities schuilgaan voor de toekomst.

Microbiomes are vast communities of microorganisms and viruses that populate all natural ecosystems. Viruses have been considered to be the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared with that of other environments. Here, we investigate the origin, evolution and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboration, we obtained DNA sequences of crAssphage from more than one-third of the world's countries and showed that the phylogeography of crAssphage is locally clustered within countries, cities and individuals. We also found fully colinear crAssphage-like genomes in both Old-World and New-World primates, suggesting that the association of crAssphage with primates may be millions of years old. Finally, by exploiting a large cohort of more than 1,000 individuals, we tested whether crAssphage is associated with bacterial taxonomic groups of the gut microbiome, diverse human health parameters and a wide range of dietary factors. We identified strong correlations with different clades of bacteria that are related to Bacteroidetes and weak associations with several diet categories, but no significant association with health or disease. We conclude that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome. ispartof: NATURE MICROBIOLOGY vol:4 issue:10 pages:1727-1736 ispartof: location:England status: published

Human betacoronaviruses OC43 and HKU1 are endemic respiratory pathogens and, while related, originated from independent zoonotic introductions. OC43 is in fact a host-range variant of the species Betacoronavirus-1 , and more closely related to bovine coronavirus (BCoV)—its presumptive ancestor—and porcine hemagglutinating encephalomyelitis virus (PHEV). The β1-coronaviruses (β1CoVs) and HKU1 employ glycan-based receptors carrying 9- O -acetylated sialic acid (9- O -Ac-Sia). Receptor binding is mediated by spike protein S, the main determinant of coronavirus host specificity. For BCoV, a crystal structure for the receptor-binding domain S1 A is available and for HKU1 a cryoelectron microscopy structure of the complete S ectodomain. However, the location of the receptor-binding site (RBS), arguably the single-most important piece of information, is unknown. Here we solved the 3.0-Å crystal structure of PHEV S1 A . We then took a comparative structural analysis approach to map the β1CoV S RBS, using the general design of 9- O -Ac-Sia-binding sites as blueprint, backed-up by automated ligand docking, structure-guided mutagenesis of OC43, BCoV, and PHEV S1 A , and infectivity assays with BCoV-S–pseudotyped vesicular stomatitis viruses. The RBS is not exclusive to OC43 and related animal viruses, but is apparently conserved and functional also in HKU1 S1 A . The binding affinity of the HKU1 S RBS toward short sialoglycans is significantly lower than that of OC43, which we attribute to differences in local architecture and accessibility, and which may be indicative for differences between the two viruses in receptor fine-specificity. Our findings challenge reports that would map the OC43 RBS elsewhere in S1 A and that of HKU1 in domain S1 B .

Objectives: Farm-level quantification of antimicrobial usage (AMU) in pig farms. Methods: In a cross-sectional study, AMU data on group treatments administered to a single batch of fattening pigs from birth to slaughter (group treatment data) and antimicrobials purchased during 1 year (purchase data) were collected at 180 pig farms in nine European countries. AMU was quantified using treatment incidence (TI) based on defined (DDDvet) and used (UDDvet) daily doses and defined (DCDvet) and used (UCDvet) course doses. Results: The majority of antimicrobial group treatments were administered to weaners (69.5% of total TIDDDvet) followed by sucklers (22.5% of total TIDDDvet). AMU varied considerably between farms with a median TIDDDvet of 9.2 and 7.1 for a standardized rearing period of 200 days based on group treatment and purchase data, respectively. In general, UDDvet and UCDvet were higher than DDDvet and DCDvet, respectively, suggesting that either the defined doses were set too low or that group treatments were often dosed too high and/or administered for too long. Extended-spectrum penicillins (31.2%) and polymyxins (24.7%) were the active substances most often used in group treatments, with the majority administered through feed or water (82%). Higher AMU at a young age was associated with higher use in older pigs. Conclusions: Collecting farm-level AMU data of good quality is challenging and results differ based on how data are collected (group treatment data versus purchase data) and reported (defined versus used daily and course doses).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect many animal species, including minks, cats, and dogs. To gain insights into SARS-CoV-2 infections in cats and dogs, we developed and validated a set of serologic assays, including ELISA and virus neutralization. Evaluation of samples from animals before they acquired coronavirus disease and samples from cats roaming SARS-CoV-2-positive mink farms confirmed the suitability of these assays for specific antibody detection. Furthermore, our findings exclude SARS-CoV-2 nucleocapsid protein as an antigen for serologic screening of cat and dog samples. We analyzed 500 serum samples from domestic cats and dogs in the Netherlands during April-May 2020. We showed 0.4% of cats and 0.2% of dogs were seropositive. Although seroprevalence in cats and dogs that had unknown SARS-CoV-2 exposure was low during the first coronavirus disease wave, our data stress the need for development of continuous serosurveillance for SARS-CoV-2 in these 2 animal species.

Since the discovery of computers, bioinformatics and computational biology have been instrumental in a wide range of discoveries in virology. These include early mathematical models of virus-host interaction, and more recently the analysis of viral nucleotide and protein sequences to track their function, epidemiology, and evolution. The genomics revolution has provided an unprecedented amount of sequence information from both viruses and their hosts. In this article, we discuss how bioinformatics allows viral sequence data to be analyzed and interpreted, including an overview of commonly used tools and examples of applications.

Several Canadian and international scholars offer commentaries on the implications of the COVID‐19 pandemic for governments and public service institutions, and fruitful directions for public administration research and practice. This first suite of commentaries focuses on the executive branch, variously considering: the challenge for governments to balance demands for accountability and learning while rethinking policy mixes as social solidarity and expert knowledge increasingly get challenged; how the policy‐advisory systems of Australia, Canada, New Zealand, and United Kingdom were structured and performed in response to the COVID‐19 crisis; whether there are better ways to suspend the accountability repertoires of Parliamentary systems than the multiparty agreement struck by the minority Liberal government with several opposition parties; comparing the Canadian government’s response to the COVID‐19 pandemic and the Global Financial Crisis and how each has brought the challenge of inequality to the fore; and whether the COVID‐19 pandemic has accelerated or disrupted digital government initiatives, reinforced traditional public administration values or more open government.

International audience; This article is a summary of the activities of the ICTV's Bacterial and Archaeal Viruses Subcommittee for the years 2018 and 2019. Highlights include the creation of a new order, 10 families, 22 subfamilies, 424 genera and 964 species. Some of our concerns about the ICTV's ability to adjust to and incorporate new DNA- and protein-based taxonomic tools are discussed.

Contains fulltext : 218214.pdf (Publisher’s version ) (Closed access) Drinking water distribution systems host complex microbial communities as biofilms that interact continuously with delivered water. Understanding the diversity, behavioural and functional characteristics will be a requisite for developing future monitoring strategies and protection against water-borne health risks. To improve understanding, this study investigates mobilisation and accumulation behaviour, microbial community structure and functional variations of biofilms developing on different pipe materials from within an operational network. Samples were collected from four pipes during a repeated flushing operation three months after an initial visit that used hydraulic forces to mobilise regenerating biofilms yet without impacting the upstream network. To minimise confounding factors, test sections were chosen with comparable daily hydraulic regimes, physical dimensions, and all connected straight of a common trunk main and within close proximity, hence similar water chemistry, pressure and age. Taxonomical results showed differences in colonising communities between pipe materials, with several genera, including the bacteria Pseudomonas and the fungi Cladosporium, present in every sample. Diverse bacterial communities dominated compared to more homogeneous fungal, or mycobiome, community distribution. The analysis of bacterial/fungal networks based on relative abundance of operational taxonomic units (OTUs) indicated microbial communities from cast iron pipes were more stable than communities from the non-ferrous pipe materials. Novel analysis of functional traits between all samples were found to be mainly associated to mobile genetic elements that play roles in determining links between cells, including phages, prophages, transposable elements, and plasmids. The use of functional traits can be considered for development in future surveillance methods, capable of delivering network condition information beyond that of limited conventional faecal indicator tests, that will help protect water quality and public health.

Background Staphylococcus pseudintermedius is a common pathogen in dogs and methicillin resistance has emerged over recent decades. According to the current guidelines, S. pseudintermedius displaying oxacillin resistance should be reported as resistant to all β-lactams. Objectives To identify possible associations between β-lactam resistance levels and clonal complexes (CCs) and/or staphylococcal cassette chromosome mec (SCCmec) types in methicillin-resistant S. pseudintermedius (MRSP). Methods MICs of oxacillin, penicillin, ampicillin, amoxicillin/clavulanic acid and cefalotin were determined by broth microdilution for 86 clinical canine MRSP isolates from Denmark and the Netherlands. PCR and sequencing were used for SCCmec typing and MLST. Results Isolates belonged to CC71 (n = 36), CC258 (n = 33), CC45 (n = 11), CC68 (n = 1) and five singleton STs. SCCmecII-III was exclusively found in CC71 and SCCmecIV was significantly associated with CC258. SCCmecV and non-typeable SCCmec types occurred in 4 and 14 isolates, respectively. SCCmecIV was associated with lower MICs of oxacillin ( Conclusions SCCmec types were associated with different CCs and with either high- or low-level resistance to different β-lactams. The finding of amoxicillin/clavulanic acid (20%) and cefalotin (70%) in vitro susceptibility across all CCs might have clinical implications, since amoxicillin/clavulanic acid and first-generation cephalosporins are first-choice antibiotics for treatment of S. pseudintermedius infections. Pharmacokinetic/pharmacodynamic and clinical outcome studies are warranted to evaluate the in vivo efficacy of these β-lactams for treatment of MRSP infections.

In addressing pandemics, science has never seemed more needed and useful, while at the same time limited and powerless. The existing contract between science and society is falling apart. A new covenant is urgently needed to navigate the days ahead.

In addressing pandemics, science has never seemed more needed and useful, while at the same time limited and powerless. The existing contract between science and society is falling apart. A new covenant is urgently needed to navigate the days ahead.

This article is a summary of the activities of the ICTV's Bacterial and Archaeal Viruses Subcommittee for the years 2018 and 2019. Highlights include the creation of a new order, 10 families, 22 subfamilies, 424 genera and 964 species. Some of our concerns about the ICTV's ability to adjust to and incorporate new DNA- and protein-based taxonomic tools are discussed.

Contains fulltext : 218215pub.pdf (Publisher’s version ) (Closed access) The colorectal cancer spectrum has changed due to population screening programs, with a shift toward adenomas and early cancers. Whether it would be a feasible option to test these adenomas for detection of Lynch syndrome (LS) patients is unclear. Through meta-analysis and systematic review, risk factors for DNA mismatch repair deficiency (dMMR) and microsatellite instability (MSI) in adenomas were identified in LS and unselected patient cohorts. Data were extracted for patient age and MMR variant together with adenoma type, grade, size, and location. A total of 41 studies were included, and contained more than 519 LS patients and 1698 unselected patients with 1142 and 2213 adenomas respectively. dMMR/MSI was present in 69.5% of conventional adenomas in LS patients, compared with 2.8% in unselected patients. In the LS cohort, dMMR/MSI was more frequently present in patients older than 60 years (82% versus 54%). dMMR/MSI was also more common in villous adenomas (84%), adenomas over 1 cm (81%), and adenomas with high grade dysplasia (88%). No significant differences were observed for dMMR/MSI in relation to MMR variants and location of adenomas. In the context of screening, we conclude that detection of dMMR/MSI in conventional adenomas of unselected patients is uncommon and might be considered as indication for LS testing. Within the LS cohort, 69.5% of LS patients could have been detected through dMMR/MSI screening of their conventional adenomas.

In addressing pandemics, science has never seemed more needed and useful, while at the same time limited and powerless. The existing contract between science and society is falling apart. A new covenant is urgently needed to navigate the days ahead.

In addressing pandemics, science has never seemed more needed and useful, while at the same time limited and powerless. The existing contract between science and society is falling apart. A new covenant is urgently needed to navigate the days ahead.

International audience; Background High antimicrobial use (AMU) and antimicrobial resistance (AMR) in veal calves remain a source of concern. As part of the EFFORT project, the association between AMU and the abundance of faecal antimicrobial resistance genes (ARGs) in veal calves in three European countries was determined. Methods In 2015, faecal samples of veal calves close to slaughter were collected from farms located in France, Germany and the Netherlands (20 farms in France, 20 farms in the Netherlands and 21 farms in Germany; 25 calves per farm). Standardized questionnaires were used to record AMU and farm characteristics. In total, 405 faecal samples were selected for DNA extraction and quantitative polymerase chain reaction to quantify the abundance (16S normalized concentration) of four ARGs [aph(3’)-III, ermB, sul2 and tetW] encoding for resistance to frequently used antimicrobials in veal calves. Multiple linear mixed models with random effects for country and farm were used to relate ARGs to AMU and farm characteristics. Results A significant positive association was found between the use of trimethoprim/sulfonamides and the concentration of sul2 in faeces from veal calves. A higher weight of calves on arrival at the farm was negatively associated with aph(3’)-III and ermB. Lower concentrations of aph(3’)-III were found at farms with non-commercial animals present. Furthermore, farms using only water for the cleaning of stables had a significantly lower abundance of faecal ermB and tetW compared with other farms. Conclusion A positive association was found between the use of trimethoprim/sulfonamides and the abundance of sul2 in faeces in veal calves. Additionally, other relevant risk factors associated with ARGs in veal calves were identified, such as weight on arrival at the farm and cleaning practices.

Many attempts to innovate local democracy focus on enhancing dialogue and fostering collaboration between citizens, local politicians and local public servants. Their architects claim, as do many academics, that these innovations have positive effects on the quality of democratic governance. But what do they actually value when they do so? We distinguish three theoretical perspectives on the contribution of local democracy innovations: (1) a problem solving perspective: democratic innovation as a precondition for more effective public policy design and delivery; (2) a democratic quality perspective: democratic innovation as a contribution to embedding process values such as inclusion, participation and empowerment into local political processes; (3) an institutional capacity perspective: democratic innovation as a means to improve the capacity of the local government organization to connect with and process the needs, aspirations and concerns of local citizens of different stripes. We present evidence from case studies of four mid-sized municipalities in the Netherlands and show that the assessment of ‘democratic innovation’ varies among politicians, decision-makers and civil servants involved in local democracy innovations. Democratic innovations are neither designed nor assessed according to a single, coherent and widely shared innovation philosophy.

Many attempts to innovate local democracy focus on enhancing dialogue and fostering collaboration between citizens, local politicians and local public servants. Their architects claim, as do many academics, that these innovations have positive effects on the quality of democratic governance. But what do they actually value when they do so? We distinguish three theoretical perspectives on the contribution of local democracy innovations: (1) a problem solving perspective: democratic innovation as a precondition for more effective public policy design and delivery; (2) a democratic quality perspective: democratic innovation as a contribution to embedding process values such as inclusion, participation and empowerment into local political processes; (3) an institutional capacity perspective: democratic innovation as a means to improve the capacity of the local government organization to connect with and process the needs, aspirations and concerns of local citizens of different stripes. We present evidence from case studies of four mid-sized municipalities in the Netherlands and show that the assessment of ‘democratic innovation’ varies among politicians, decision-makers and civil servants involved in local democracy innovations. Democratic innovations are neither designed nor assessed according to a single, coherent and widely shared innovation philosophy.

In addressing pandemics, science has never seemed more needed and useful, while at the same time limited and powerless. The existing contract between science and society is falling apart. A new covenant is urgently needed to navigate the days ahead.

Many attempts to innovate local democracy focus on enhancing dialogue and fostering collaboration between citizens, local politicians and local public servants. Their architects claim, as do many academics, that these innovations have positive effects on the quality of democratic governance. But what do they actually value when they do so? We distinguish three theoretical perspectives on the contribution of local democracy innovations: (1) a problem solving perspective: democratic innovation as a precondition for more effective public policy design and delivery; (2) a democratic quality perspective: democratic innovation as a contribution to embedding process values such as inclusion, participation and empowerment into local political processes; (3) an institutional capacity perspective: democratic innovation as a means to improve the capacity of the local government organization to connect with and process the needs, aspirations and concerns of local citizens of different stripes. We present evidence from case studies of four mid-sized municipalities in the Netherlands and show that the assessment of ‘democratic innovation’ varies among politicians, decision-makers and civil servants involved in local democracy innovations. Democratic innovations are neither designed nor assessed according to a single, coherent and widely shared innovation philosophy.

The genus Enterovirus (EV) of the family Picornaviridae includes poliovirus, coxsackieviruses, echoviruses, numbered enteroviruses and rhinoviruses. These diverse viruses cause a variety of diseases, including non-specific febrile illness, hand-foot-and-mouth disease, neonatal sepsis-like disease, encephalitis, paralysis and respiratory diseases. In recent years, several non-polio enteroviruses (NPEVs) have emerged as serious public health concerns. These include EV-A71, which has caused epidemics of hand-foot-and-mouth disease in Southeast Asia, and EV-D68, which recently caused a large outbreak of severe lower respiratory tract disease in North America. Infections with these viruses are associated with severe neurological complications. For decades, most research has focused on poliovirus, but in recent years, our knowledge of NPEVs has increased considerably. In this Review, we summarize recent insights from enterovirus research with a special emphasis on NPEVs. We discuss virion structures, host-receptor interactions, viral uncoating and the recent discovery of a universal enterovirus host factor that is involved in viral genome release. Moreover, we briefly explain the mechanisms of viral genome replication, virion assembly and virion release, and describe potential targets for antiviral therapy. We reflect on how these recent discoveries may help the development of antiviral therapies and vaccines. ispartof: NATURE REVIEWS MICROBIOLOGY vol:16 issue:6 pages:368-381 ispartof: location:England status: published

Background: In recent years, ESBL/AmpC-producing Escherichia coli (ESBL/AmpC-EC) have been isolated with increasing frequency from animals, food, environmental sources and humans. With incomplete and scattered evidence, the contribution to the human carriage burden from these reservoirs remains unclear. Objectives: To quantify molecular similarities between different reservoirs as a first step towards risk attribution. Methods: Pooled data on ESBL/AmpC-EC isolates were recovered from 35 studies in the Netherlands comprising >27 000 samples, mostly obtained between 2005 and 2015. Frequency distributions of ESBL/AmpC genes from 5808 isolates and replicons of ESBL/AmpC-carrying plasmids from 812 isolates were compared across 22 reservoirs through proportional similarity indices (PSIs) and principal component analyses (PCAs). Results: Predominant ESBL/AmpC genes were identified in each reservoir. PCAs and PSIs revealed close human-animal ESBL/AmpC gene similarity between human farming communities and their animals (broilers and pigs) (PSIs from 0.8 to 0.9). Isolates from people in the general population had higher similarities to those from human clinical settings, surface and sewage water and wild birds (0.7-0.8), while similarities to livestock or food reservoirs were lower (0.3-0.6). Based on rarefaction curves, people in the general population had more diversity in ESBL/AmpC genes and plasmid replicon types than those in other reservoirs. Conclusions: Our 'One Health' approach provides an integrated evaluation of the molecular relatedness of ESBL/AmpC-EC from numerous sources. The analysis showed distinguishable ESBL/AmpC-EC transmission cycles in different hosts and failed to demonstrate a close epidemiological linkage of ESBL/AmpC genes and plasmid replicon types between livestock farms and people in the general population.

Bacterial antimicrobial resistance (AMR) is constantly evolving and horizontal gene transfer through plasmids plays a major role. The identification of plasmid characteristics and their association with different bacterial hosts provides crucial knowledge that is essential to understand the contribution of plasmids to the transmission of AMR determinants. Molecular identification of plasmid and strain genotypes elicits a distinction between spread of AMR genes by plasmids and dissemination of these genes by spread of bacterial clones. For this reason several methods are used to type the plasmids, e.g. PCR-based replicon typing (PBRT) or relaxase typing. Currently, there are 28 known plasmid types in Enterobacteriaceae distinguished by PBRT. Frequently reported plasmids [IncF, IncI, IncA/C, IncL (previously designated IncL/M), IncN and IncH] are the ones that bear the greatest variety of resistance genes. The purpose of this review is to provide an overview of all known AMR-related plasmid families in Enterobacteriaceae, the resistance genes they carry and their geographical distribution.

Comprehensive strategies to improve on-farm antimicrobial use (AMU) are needed to contain antimicrobial resistance (AMR). Little is known about farmers' motivating and enabling factors, and about their influence on AMU. In a cross-sectional online survey, Dutch dairy, veal and pig farmers (n=457) reported their on-farm AMU as "Defined Daily Dose Animal" per year (DDDAF) and completed a detailed questionnaire on their view, knowledge and behavior towards AMU and AMR. Exploratory factor analysis (EFA) on the questionnaire items identified four psychological factors labeled as 'referent beliefs', 'perceived risk', 'knowledge', and 'undesired attitude to regulations'. Linear regression was done to explore the relationship between the obtained factors and on-farm AMU across the three animal sectors. Dairy farmers showed the highest factor scores for 'knowledge' and the lowest for 'perceived risk'. 'Knowledge' scores were significantly and inversely related to AMU (P=0.0004). Borderline significant associations with AMU were found for 'perceived risk' and 'undesired attitude to regulations' (negative and positive relationships respectively). There were no apparent differences for these relationships between the three livestock sectors. Behavioral interventions in farmers such as educational campaigns or increased support by veterinarians could empower farmers with more prudent and rational practices, eventually reducing AMU in food animals.

Purpose: Top managers guide organizational strategy and practices, but their role in the employment of older workers is understudied. We study the effects that age-related workplace norms of top managers have on organizations’ recruitment and retention practices regarding older workers. We investigate two types of age-related workplace norms, namely age equality norms (whether younger and older workers should be treated equally) and retirement age norms (when older workers are expected to retire) while controlling for organizational and national contexts.Data and methods: Data collected among top managers of 1,088 organizations from six European countries were used for the study. Logistic regression models were run to estimate the effects of age-related workplace norms on four different organizational outcomes: (a) recruiting older workers, (b) encouraging working until normal retirement age, (c) encouraging working beyond normal retirement age, and (d) rehiring retired former employees.Results: Age-related workplace norms of top managers affect their organizations’ practices, but in different ways. Age equality norms positively affect practices before the boundary of normal retirement age (Outcomes a and b), whereas retirement age norms positively affect practices after the boundary of normal retirement age (Outcomes c and d).Implications: Changing age-related workplace norms of important actors in organizations may be conducive to better employment opportunities and a higher level of employment participation of older workers. However, care should be taken to target the right types of norms, since targeting different norms may yield different outcomes.

Objectives Patients with chronic obstructive pulmonary disease (COPD) constitute a potentially susceptible group towards environmental exposures such as livestock farm emissions, given their compromised respiratory health status. The primary aim of this study was to examine the association between livestock exposure and comorbidities and coexisting symptoms and infections in COPD patients. Methods Data were collected from 1828 COPD patients (without co-occurring asthma) registered in 23 general practices and living in a rural area with a high livestock density. Prevalence of comorbid diseases/disorders and coexisting symptoms/infections were based on electronic health records from the year 2012. Various indicators of individual exposure to livestock were estimated based on residential addresses, using a geographic information system. Results At least one comorbid disorder was present in 69% of the COPD patients (especially cardiac disorders and depression, while 49% had at least one coexisting symptom and/or infection (especially upper respiratory tract infections, respiratory symptoms and pneumonia). Half of the COPD-patients resided less than 500 m of the nearest farm. Some positive as well as inverse associations were found between the examined outcomes and exposure estimates, although not consistent. Conclusions Despite the high prevalence of coexisting chronic and acute conditions presented in primary care by in COPD patients, this investigation found no convincing evidence for an association with livestock exposure estimates. There is a need for a replication of the present findings in studies with a longitudinal design, on different groups of potentially susceptible patients. Future research should also elucidate the biological plausibility of possible protective effects of exposure.

Highlights • Overexpression of porcine APN in cells does not confer susceptibility to PEDV. • Knockout APN expression in PEDV-susceptible cells has no effect on PEDV infection. • Results demonstrate that APN is not essential for PEDV cell entry., Porcine epidemic diarrhea virus (PEDV) is an emerging pathogenic coronavirus that causes a significant economic burden to the swine industry. The virus infects the intestinal epithelium and causes villous atrophy, resulting in diarrhea and dehydration. Interaction of the viral spike (S) surface glycoprotein − through its S1 subunit − with the host cell receptor is the first step in infection and the main determinant for virus tropism. As for several other alphacoronaviruses including the porcine transmissible gastroenteritis virus (TGEV) and the human coronavirus 229E (HCoV-229E), the aminopeptidase N (APN) protein was reported to be a functional receptor for PEDV. In this study we examined the role of APN as a receptor. We show that overexpression of porcine APN renders MDCK cells susceptible to TGEV, but not to PEDV. Consistently, unlike TGEV-S1, PEDV-S1 exhibited no binding to cell-surface expressed APN or to a soluble version of APN. Moreover, preincubation of these viruses with soluble APN or pretreatment of APN expressing ST cells with soluble TGEV-S1 blocked TGEV infection, but had no effect on infection by PEDV. The combined observations indicated that APN is not required for PEDV infection. To definitively prove this conclusion, we applied CRISPR/Cas9 genome engineering to knock out APN expression in PEDV-susceptible porcine (ST) and human cell lines (Huh7 and HeLa). As a consequence these cells no longer bound TGEV-S1 and HCoV-229E-S1 at their surface and were resistant to infection by the corresponding viruses. However, genetic ablation of APN expression had no effect on their infectability by PEDV, demonstrating that APN is not essential for PEDV cell entry.

International audience; Middle East respiratory syndrome coronavirus (MERS-CoV) targets the epithelial cells of the respiratory tract both in humans and in its natural host, the dromedary camel. Virion attachment to host cells is mediated by 20-nm-long homotrimers of spike envelope protein S. The N-terminal subunit of each S protomer, called S1, folds into four distinct domains designated S1A through S1D Binding of MERS-CoV to the cell surface entry receptor dipeptidyl peptidase 4 (DPP4) occurs via S1B We now demonstrate that in addition to DPP4, MERS-CoV binds to sialic acid (Sia). Initially demonstrated by hemagglutination assay with human erythrocytes and intact virus, MERS-CoV Sia-binding activity was assigned to S subdomain S1A When multivalently displayed on nanoparticles, S1 or S1A bound to human erythrocytes and to human mucin in a strictly Sia-dependent fashion. Glycan array analysis revealed a preference for α2,3-linked Sias over α2,6-linked Sias, which correlates with the differential distribution of α2,3-linked Sias and the predominant sites of MERS-CoV replication in the upper and lower respiratory tracts of camels and humans, respectively. Binding is hampered by Sia modifications such as 5-N-glycolylation and (7,)9-O-acetylation. Depletion of cell surface Sia by neuraminidase treatment inhibited MERS-CoV entry of Calu-3 human airway cells, thus providing direct evidence that virus-Sia interactions may aid in virion attachment. The combined observations lead us to propose that high-specificity, low-affinity attachment of MERS-CoV to sialoglycans during the preattachment or early attachment phase may form another determinant governing the host range and tissue tropism of this zoonotic pathogen

The Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and often lethal respiratory illness in humans, and no vaccines or specific treatments are available. Infections are initiated via binding of the MERS-CoV spike (S) glycoprotein to sialosides and dipeptidyl-peptidase 4 (the attachment and entry receptors, respectively). To understand MERS-CoV engagement of sialylated receptors, we determined the cryo-EM structures of S in complex with 5-N-acetyl neuraminic acid, 5-N-glycolyl neuraminic acid, sialyl-LewisX, α2,3-sialyl-N-acetyl-lactosamine and α2,6-sialyl-N-acetyl-lactosamine at 2.7–3.0 Å resolution. We show that recognition occurs via a conserved groove that is essential for MERS-CoV S-mediated attachment to sialosides and entry into human airway epithelial cells. Our data illuminate MERS-CoV S sialoside specificity and suggest that selectivity for α2,3-linked over α2,6-linked receptors results from enhanced interactions with the former class of oligosaccharides. This study provides a structural framework explaining MERS-CoV attachment to sialoside receptors and identifies a site of potential vulnerability to inhibitors of viral entry., Cryo-EM structures of MERS-CoV S glycoprotein trimer in complex with different sialosides reveal how the virus engages with sialylated receptors, providing insight into receptor specificity and selectivity.

Antimicrobial use (AMU) in humans and animals facilitates the emergence of antimicrobial resistance (AMR). With increasing AMR being recognised as a major global threat for public health, responsible AMU is strongly advocated in both human and veterinary medicine. Knowledge on factors influencing antimicrobial prescribing behaviour of companion animal veterinarians is needed to promote responsible AMU in companion animals and to improve compliance with current legislation and guidelines. The present study aimed to quantitively investigate attitudes and perceptions of companion animal veterinarians towards AMU and AMR and to identify associations with demographic characteristics as possible explanatory variables. A self-administered questionnaire was developed based upon an earlier qualitative interview study, and 1608 potential participants (i.e. practising companion animal veterinarians) were invited. The questionnaire included questions addressing general descriptives of the respondents and questions with 6-point Likert scale statements, to assess attitudes towards AMU, AMR, factors influencing antimicrobial prescribing, and possible options to support responsible AMU. The response rate was 32% (22% when complete questionnaires considered). Categorical Principal Component Analysis (CATPCA) was conducted on 76 Likert scale questions. This resulted in a final model with 37 questions explaining 38.7% of the variance of the question scores, with three underlying dimensions ("attitudinal profiles"). Additionally, general descriptives were added to the CATPCA as possible explanatory variables. The first dimension, related to "social responsibility" was positively associated with veterinarians working in clinics dedicated to companion animals, with veterinarians working in a referral clinic, and with more experienced veterinarians. The second dimension was related to "scepticism", which was positively associated with being a male veterinarian and with more experienced veterinarians. The third dimension was related to "risk avoidance", especially regarding surgical procedures, and was negatively associated with veterinarians working in clinics in urban areas and with veterinarians working part-time. Antimicrobial prescribing behaviour was self-reported to be well considered, and respondents did not see economic drivers as important influencing factors. The unwillingness of owners and financial constraints were perceived as important barriers for performing further diagnostics. To improve AMU, a multifaceted approach, taking differences between companion animal veterinarians (e.g., in experience and gender) and differences in work situation (e.g., full-time versus part-time) into account, should be directed at companion animal veterinarians and owners. Moreover, a joint and comprehensive effort of several stakeholders, like veterinary nurses, guideline developers, pharmaceutical industry, and providers of diagnostics, is needed to optimise AMU in companion animals.

Middle East respiratory syndrome coronavirus (MERS-CoV) uses the S1(B) domain of its spike protein to bind to dipeptidyl peptidase 4 (DPP4), its functional receptor, and its S1(A) domain to bind to sialic acids. The tissue localization of DPP4 in humans, bats, camelids, pigs, and rabbits generally correlates with MERS-CoV tropism, highlighting the role of DPP4 in virus pathogenesis and transmission. However, MERS-CoV S1(A) does not indiscriminately bind to all α2,3-sialic acids, and the species-specific binding and tissue distribution of these sialic acids in different MERS-CoV-susceptible species have not been investigated. We established a novel method to detect these sialic acids on tissue sections of various organs of different susceptible species by using nanoparticles displaying multivalent MERS-CoV S1(A). We found that the nanoparticles specifically bound to the nasal epithelial cells of dromedary camels, type II pneumocytes in human lungs, and the intestinal epithelial cells of common pipistrelle bats. Desialylation by neuraminidase abolished nanoparticle binding and significantly reduced MERS-CoV infection in primary susceptible cells. In contrast, S1(A) nanoparticles did not bind to the intestinal epithelium of serotine bats and frugivorous bat species, nor did they bind to the nasal epithelium of pigs and rabbits. Both pigs and rabbits have been shown to shed less infectious virus than dromedary camels and do not transmit the virus via either contact or airborne routes. Our results depict species-specific colocalization of MERS-CoV entry and attachment receptors, which may be relevant in the transmission and pathogenesis of MERS-CoV. IMPORTANCE MERS-CoV uses the S1(B) domain of its spike protein to attach to its host receptor, dipeptidyl peptidase 4 (DPP4). The tissue localization of DPP4 has been mapped in different susceptible species. On the other hand, the S1(A) domain, the N-terminal domain of this spike protein, preferentially binds to several glycotopes of α2,3-sialic acids, the attachment factor of MERS-CoV. Here we show, using a novel method, that the S1(A) domain specifically binds to the nasal epithelium of dromedary camels, alveolar epithelium of humans, and intestinal epithelium of common pipistrelle bats. In contrast, it does not bind to the nasal epithelium of pigs or rabbits, nor does it bind to the intestinal epithelium of serotine bats and frugivorous bat species. This finding supports the importance of the S1(A) domain in MERS-CoV infection and tropism, suggests its role in transmission, and highlights its potential use as a component of novel vaccine candidates.

Positive-stranded RNA viruses extensively remodel host cell architecture to enable viral replication. Here we examined the poorly understood formation of specialized membrane compartments which are critical sites for the synthesis of the viral genome. We show that the replication compartments (RCs) of enteroviruses are created through novel membrane contact sites that recruit host lipid droplets (LDs) to the RCs. Viral proteins tether the RCs to the LDs and interact with the host lipolysis machinery to enable transfer of fatty acids from LDs, thereby providing lipids essential for RC biogenesis. Inhibiting the formation of the membrane contact sites between LDs and RCs or inhibition of the lipolysis pathway disrupts RC biogenesis and enterovirus replication. Our data illuminate mechanistic and functional aspects of organelle remodeling in viral infection and establish that pharmacological targeting of contact sites linking viral and host compartments is a potential strategy for antiviral development.

Guanabara Bay is a tropical estuarine ecosystem that receives massive anthropogenic impacts from the metropolitan region of Rio de Janeiro. This ecosystem suffers from an ongoing eutrophication process that has been shown to promote the emergence of potentially pathogenic bacteria, giving rise to public health concerns. Although previous studies have investigated how environmental parameters influence the microbial community of Guanabara Bay, they often have been limited to small spatial and temporal gradients and have not been integrated into predictive mathematical models. Our objective was to fill this knowledge gap by building models that could predict how temperature, salinity, phosphorus, nitrogen and transparency work together to regulate the abundance of bacteria, chlorophyll and Vibrio (a potential human pathogen) in Guanabara Bay. To that end, we built artificial neural networks to model the associations between these variables. These networks were carefully validated to ensure that they could provide accurate predictions without biases or overfitting. The estimated models displayed high predictive capacity (Pearson correlation coefficients ≥0.67 and root mean square error ≤ 0.55). Our findings showed that temperature and salinity were often the most important factors regulating the abundance of bacteria, chlorophyll and Vibrio (absolute importance ≥5) and that each of these has a unique level of dependence on nitrogen and phosphorus for their growth. These models allowed us to estimate the Guanabara Bay microbiome's response to changes in environmental conditions, which allowed us to propose strategies for the management and remediation of Guanabara Bay.

This chapter discusses the findings from previous chapters, points to future policy challenges and presents suggestions for future research. The picture of self-employment as precarious work in Europe is diverse and far from uniform, but with respect to the different dimensions one may conclude – though with a degree of caution – that: (1) for many self-employed current income is not an immediate or pressing problem, although for some this is mostly because their income from self-employment is not the only source of income. Still, many self-employed lack the opportunity to put something aside for a rainy day; (2) in various countries, social benefits and regulatory protection are relatively poor, though very much depending on specific national conditions; and (3) uncertainty for self-employed is typically high, but also often regarded part of the job. Directions for future research include research on changes in employment biographies over time, employment insecurity and social protection.

15 pages, 5 figures, 1 table, supplemental Information https://doi.org/10.1016/j.chom.2019.08.019, Phages are increasingly recognized as important members of host-associated microbiomes, with a vast genomic diversity. The new frontier is to understand how phages may affect higher order processes, such as in the context of host-microbe interactions. Here, we use marine sponges as a model to investigate the interplay between phages, bacterial symbionts, and eukaryotic hosts. Using viral metagenomics, we find that sponges, although massively filtering seawater, harbor species-specific and even individually unique viral signatures that are taxonomically distinct from other environments. We further discover a symbiont phage-encoded ankyrin-domain-containing protein, which is widely spread in phages of many host-associated contexts including human. We confirm in macrophage infection assays that the ankyrin protein (ANKp) modulates the eukaryotic host immune response against bacteria. We predict that the role of ANKp in nature is to facilitate coexistence in the tripartite interplay between phages, symbionts, and sponges and possibly many other host-microbe associations, We acknowledge funding by the DFG CRC1182 to U.H. (TPB1), T.L. (TPA4), P.R. (TPC2), and A.K. (TPC3). M.T.J. was supported by a grant of the German Excellence Initiative to the Graduate School of Life Sciences, University of Würzburg, and the Young Investigator Award of CRC1182. S.M.M. was supported by the Studienstiftung des Deutschen Volkes

15 pages, 15 figures, 1 tables, supporting information https://doi.org/10.1016/j.cell.2019.03.040, Microbes drive most ecosystems and are modulated by viruses that impact their lifespan, gene flow, and metabolic outputs. However, ecosystem-level impacts of viral community diversity remain difficult to assess due to classification issues and few reference genomes. Here, we establish an ∼12-fold expanded global ocean DNA virome dataset of 195,728 viral populations, now including the Arctic Ocean, and validate that these populations form discrete genotypic clusters. Meta-community analyses revealed five ecological zones throughout the global ocean, including two distinct Arctic regions. Across the zones, local and global patterns and drivers in viral community diversity were established for both macrodiversity (inter-population diversity) and microdiversity (intra-population genetic variation). These patterns sometimes, but not always, paralleled those from macro-organisms and revealed temperate and tropical surface waters and the Arctic as biodiversity hotspots and mechanistic hypotheses to explain them. Such further understanding of ocean viruses is critical for broader inclusion in ecosystem models, Tara Oceans (that includes both the Tara Oceans and Tara Oceans Polar Circle expeditions) would not exist without the leadership of the Tara Expeditions Foundation and the continuous support of 23 institutes (https://oceans.taraexpeditions.org). We further thank the commitment of the following sponsors: CNRS (in particular Groupement de Recherche GDR3280 and the Research Federation for the study of Global Ocean Systems Ecology and Evolution, FR2022/Tara Oceans-GOSEE), European Molecular Biology Laboratory (EMBL), Genoscope/CEA, The French Ministry of Research, and the French Government “Investissements d’Avenir” programmes OCEANOMICS (ANR-11-BTBR-0008), FRANCE GENOMIQUE (ANR-10-INBS-09-08), MEMO LIFE (ANR-10-LABX-54), and PSL∗ Research University (ANR-11-IDEX-0001-02). We also thank the support and commitment of Agnès b. and Etienne Bourgois, the Prince Albert II de Monaco Foundation, the Veolia Foundation, Region Bretagne, Lorient Agglomeration, Serge Ferrari, Worldcourier, and KAUST

EFFORT consortium members=Haitske Graveland (UUVM), Alieda van Essen (WBVR), Bruno Gonzalez-Zorn (UCM), Gabriel Moyano (UCM), Pascal Sanders (ANSES), Claire Chauvin (ANSES), Julie David (ANSES), Antonio Battisti (IZSLT), Andrea Caprioli (IZSLT), Thomas Blaha (TIHO), Katharina Wadepohl (TIHO), Maximiliane Brandt (TIHO), Tine Hald (DTU), Ana Sofia Ribeiro Duarte (DTU), Dariusz Wasyl (NVRI), Magdalena Skar_zynska (NVRI), Magdalena Zaja˛c (NVRI), Andrzej Hoszowski (deceased) (NVRI), Hristo Daskalov (NDRVI), Helmut W. Saatkamp (BEC) and Katharina D. C. Sta¨ rk (SAFOSO).; International audience; Previous studies in food-producing animals have shown associations between antimicrobial use (AMU) and resistance (AMR) in specifically isolated bacterial species. Multi-country data are scarce and only describe between-country differences. Here we investigate associations between the pig faecal mobile resistome and characteristics at the farm-level across Europe.A cross-sectional study was conducted among 176 conventional pig farms from nine European countries. Twenty-five faecal samples from fattening pigs were pooled per farm and acquired resistomes were determined using shotgun metagenomics and the Resfinder reference database, i.e. the full collection of horizontally acquired AMR genes (ARGs). Normalized fragments resistance genes per kilobase reference per million bacterial fragments (FPKM) were calculated. Specific farm-level data (AMU, biosecurity) were collected. Random-effects meta-analyses were performed by country, relating farm-level data to relative ARG abundances (FPKM).Total AMU during fattening was positively associated with total ARG (total FPKM). Positive associations were particularly observed between widely used macrolides and tetracyclines, and ARGs corresponding to the respective antimicrobial classes. Significant AMU-ARG associations were not found for β-lactams and only few colistin ARGs were found, despite high use of these antimicrobial classes in younger pigs. Increased internal biosecurity was directly related to higher abundances of ARGs mainly encoding macrolide resistance. These effects of biosecurity were independent of AMU in mutually adjusted models.Using resistome data in association studies is unprecedented and adds accuracy and new insights to previously observed AMU-AMR associations. Major components of the pig resistome are positively and independently associated with on-farm AMU and biosecurity conditions.

Objectives: To control the emerging threat of antimicrobial resistance, international policy appeals for appropriate monitoring of antimicrobial usage (AMU) at supranational, species and farm level. The aim of this study was to quantify AMU in broilers at farm and flock level in nine European countries. Methods: Antimicrobial treatment data of one flock and purchased antimicrobials over one year were collected at 181 European broiler farms. Afterwards AMU was quantified using treatment incidence (TI) per 100 days based on Defined Daily Dose (DDDvet), Defined Course Dose (DCDvet) or Used Daily Dose (UDDvet) values. Total AMU at flock level was obtained by summing the TIDDDvet of all treatments in the sampled flock (TIDDDvetFl*). Results: The median TIDDDvetFl* was 9.0 (95% CI 5.5-10.8), meaning that broilers were treated with antimicrobials during 9% of their rearing period. TIDDDvetFl* varied considerably within and between countries. However, in every country at least one untreated flock was present. Average TIDDDvetFl* at country level ranged from 3.3 to 36.7. Polymyxins, extended-spectrum aminopenicillins and fluoroquinolones were the most used antimicrobials, accounting for 26%, 26% and 18% of total AMU, respectively. Twenty-six percent of the farms started a treatment on day 1 of production, and 49% of overall AMU was administered within the first week. Conclusions: Results show that rearing broilers without AMU is feasible. However, a huge variation in AMU in terms of amount, moment of administration and antimicrobial classes was observed. This shows that there is still ground to be covered when it comes to AMU on broiler farms.

Exposure to moisture-damaged indoor environments is associated with adverse respiratory health effects, but responsible factors remain unidentified. In order to explore possible mechanisms behind these effects, the oxidative capacity and hemolytic activity of settled dust samples (n = 25) collected from moisture-damaged and non-damaged schools in Spain, the Netherlands, and Finland were evaluated and matched against the microbial content of the sample. Oxidative capacity was determined with plasmid scission assay and hemolytic activity by assessing the damage to isolated human red blood cells. The microbial content of the samples was measured with quantitative PCR assays for selected microbial groups and by analyzing the cell wall markers ergosterol, muramic acid, endotoxins, and glucans. The moisture observations in the schools were associated with some of the microbial components in the dust, and microbial determinants grouped together increased the oxidative capacity. Oxidative capacity was also affected by particle concentration and country of origin. Two out of 14 studied dust samples from moisture-damaged schools demonstrated some hemolytic activity. The results indicate that the microbial component connected with moisture damage is associated with increased oxidative stress and that hemolysis should be studied further as one possible mechanism contributing to the adverse health effects of moisture-damaged buildings.

International audience; Coronaviruses cause respiratory tract infections in humans and outbreaks of deadly pneumonia worldwide. Infections are initiated by the transmembrane spike (S) glycoprotein, which binds to host receptors and fuses the viral and cellular membranes. To understand the molecular basis of coronavirus attachment to oligosaccharide receptors, we determined cryo-EM structures of coronavirus OC43 S glycoprotein trimer in isolation and in complex with a 9-O-acetylated sialic acid. We show that the ligand binds with fast kinetics to a surface-exposed groove and that interactions at the identified site are essential for S-mediated viral entry into host cells, but free monosaccharide does not trigger fusogenic conformational changes. The receptor-interacting site is conserved in all coronavirus S glycoproteins that engage 9-O-acetyl-sialogycans, with an architecture similar to those of the ligand-binding pockets of coronavirus hemagglutinin esterases and influenza virus C/D hemagglutinin-esterase fusion glycoproteins. Our results demonstrate these viruses evolved similar strategies to engage sialoglycans at the surface of target cells.