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Abstract Mussels form extensive beds in rocky intertidal habitats on temperate seashores worldwide. They are foundation species because their beds host many invertebrates. Mussels and their associated species differ taxonomically among biogeographic regions, but all mussel beds exhibit similar structural and functional properties. Therefore, we investigated if rocky-intertidal mussel beds from around the globe host associated communities that are functionally similar despite their underlying taxonomic differences. We gathered datasets on the abundance of invertebrates found in rocky-intertidal mussel beds from the eastern and western boundaries of the Pacific and Atlantic Oceans from both hemispheres and, then, we compared their taxonomic and functional properties. Taxonomic composition differed markedly among coasts when analyzed at the taxonomic resolution reported by the surveys (often species). However, taxonomic groups with similar ecologies (28 groups including barnacles, decapods, gastropods, polychaetes, etc.) were more universally present in mussel beds. Concomitantly, functional categories of trophic level, body type, and mobility were almost always present on all studied coasts. These taxonomic groups and trait categories, however, showed regional patterns based on their relative abundances. Overall, the ability of mussel beds to host a core community type based on taxonomic groups and functional traits emphasizes their importance for biodiversity and community functioning, making them critical organisms to preserve.

In the past decade, noble gases have emerged as highly promising neuroprotective agents. Previous studies have demonstrated the efficacy of argon neuroprotection in rodent models of cerebral ischemia. The objective of the present pre-clinical study was to confirm the neuroprotective effect of argon in a non-human primate model of endovascular ischemic stroke. Thirteen adult Macaca mulatta were subjected to a focal cerebral ischemia induced by a transient (90 min) middle cerebral artery occlusion (tMCAO). The monkeys were randomly allocated to a control group (n = 8) and an argon group (n = 5). Pre-mixed gas (40-60 oxygen-argon) was applied 30 min after the onset of tMCAO to 30 min after reperfusion. Infarct volumes were measured from the MRI scans conducted 1 hour and 1 month after the reperfusion. A clinical neurological assessment was performed 24 hours and 1 month after tMCAO. Our results show that Argon dramatically reduced ischemic core volume after ischemia compared to the control group with a long-lasting improvement of post-stroke infarct volume at 1 month. In addition, the neurological scale suggests a better prognosis in argon-treated animals without reaching the significance threshold. These pre-clinical results in gyrencephalic non-human primates support the potential use of this therapeutic approach for future clinical studies., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: At the time of the study GF was the Air Liquide director of early drug development but did not participate in study conduction or data analysis.VL and BT share together with institutions (CNRS, AMU and Air Liquide) the property of patent (EP3791886B1 and US11717635B2), which partly cover the research of the present study. The other authors report no conflicts of interest.

Conventional dendritic cells (cDCs) are antigen-presenting cells (APCs) that play a central role in linking innate and adaptive immunity. cDCs have been well described in a number of different mammalian species, but remain poorly characterised in the chicken. In this study, we use previously described chicken cDC specific reagents, a novel gene-edited chicken line and single-cell RNA sequencing (scRNAseq) to characterise chicken splenic cDCs. In contrast to mammals, scRNAseq analysis indicates that the chicken spleen contains a single, chemokine receptor XCR1 expressing, cDC subset. By sexual maturity the XCR1 + cDC population is the most abundant mononuclear phagocyte cell subset in the chicken spleen. scRNAseq analysis revealed substantial heterogeneity within the chicken splenic XCR1 + cDC population. Immature MHC class II (MHCII) LOW XCR1 + cDCs expressed a range of viral resistance genes. Maturation to MHCII HIGH XCR1 + cDCs was associated with reduced expression of anti-viral gene expression and increased expression of genes related to antigen presentation via the MHCII and cross-presentation pathways. To visualise and transiently ablate chicken XCR1 + cDCs in situ , we generated XCR1 -iCaspase9-RFP chickens using a CRISPR-Cas9 knockin transgenesis approach to precisely edit the XCR1 locus, replacing the XCR1 coding region with genes for a fluorescent protein (TagRFP), and inducible Caspase 9. After inducible ablation, the chicken spleen is initially repopulated by immature CD1.1 + XCR1 + cDCs. XCR1 + cDCs are abundant in the splenic red pulp, in close association with CD8 + T-cells. Knockout of XCR1 prevented this clustering of cDCs with CD8 + T-cells. Taken together these data indicate a conserved role for chicken and mammalian XCR1 + cDCs in driving CD8 + T-cells responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Wu, Shih, Macdonald, Meunier, Hogan, Chintoan-Uta, Gilhooley, Hu, Beltran, Henderson, Sang, Stevens, McGrew and Balic.)

Group level analyses of functional regions involved in voice perception show evidence of 3 sets of bilateral voice-sensitive activations in the human prefrontal cortex, named the anterior, middle and posterior Frontal Voice Areas (FVAs). However, the relationship with the underlying sulcal anatomy, highly variable in this region, is still unknown. We examined the inter-individual variability of the FVAs in conjunction with the sulcal anatomy. To do so, anatomical and functional MRI scans from 74 subjects were analyzed to generate individual contrast maps of the FVAs and relate them to each subject's manually labeled prefrontal sulci. We report two major results. First, the frontal activations for the voice are significantly associated with the sulcal anatomy. Second, this correspondence with the sulcal anatomy at the individual level is a better predictor than coordinates in the MNI space. These findings offer new perspectives for the understanding of anatomical-functional correspondences in this complex cortical region. They also shed light on the importance of considering individual-specific variations in subject's anatomy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: We aimed to describe the UK Pseudomonas aeruginosa population structure amongst people with cystic fibrosis (PWCF), and to examine evidence for cross-infection., Methods: Variable Number Tandem Repeat (VNTR) typing was performed on 4640 isolates from 2619 PWCF received from 55 hospital laboratories between 2017 and 2019. A combination of whole genome sequence (WGS)-based analysis of four clusters from one hospital, and epidemiological analysis of shared strains in twelve hospitals evaluated cross-infection., Results: Of 2619 PWCF, 1324 (51%) harboured common clusters or known transmissible strains, while 1295 carried unique strains/those shared among small numbers of patients. Of the former, 9.5% (250 patients) harboured the Liverpool epidemic strain (LES), followed in prevalence by clone C (7.8%; 205 patients), cluster A (5%;130 patients), and cluster D (3.6%; 94 patients). WGS analysis of 10 LES isolates, 9 of cluster D and 6 isolates each of cluster A and clone C from one hospital revealed LES formed the tightest cluster (between 7 and 205 SNPs), and cluster D the loosest (between 53 and 1531 SNPs). Hospital-specific shared strains were found in some centres, although cross-infection was largely historical, with few new acquisitions. Fifty-nine PWCF (2.3%) harboured "high-risk" clones; one ST235 isolate carried a bla IMP-1 allele., Conclusion: Of 2619 PWCF who had P. aeruginosa isolates submitted for VNTR, 51% harboured either common clusters or known transmissible strains, of which LES was the most common. Limited evidence of recent patient-to-patient strain transmission was found, suggesting cross-infection prevention measures and surveillance effectively reduce transmission., Competing Interests: Declaration of Competing Interest None of the authors have had any conflicts of interest to declare relating to this study., (Copyright © 2023. Published by Elsevier B.V.)

Introduction. Combination of PCR and Elek testing to identify toxigenic corynebacteria has revealed organisms described as non-toxigenic toxin-gene bearing (NTTB) Corynebacterium diphtheriae or C. ulcerans (i.e. PCR tox positive; Elek negative). These organisms carry part or all of tox , but are unable to express diphtheria toxin (DT) and present a challenge to clinical and public health case management. Gap analysis/Hypothesis. There are few data on the theoretical risk of NTTB reversion to toxigenicity. This unique cluster and subsequent epidemiologically linked isolates allowed the opportunity to determine any change in DT expression status. Aim. To characterize a cluster of infections due to NTTB in a skin clinic and subsequent cases in two household contacts. Methodology. Epidemiological and microbiological investigations were carried out according to existing national guidance at the time. Susceptibility testing used gradient strips. The tox operon analysis and multi-locus sequence typing (MLST) was derived from whole-genome sequencing. Alignment of the tox operon and phylogenetic analyses were performed using clustalW, mega, the public core-genome MLST (cgMLST) scheme and an in-house bioinformatic single nucleotide polymorphism (SNP) typing pipeline. Results. Isolates of NTTB C. diphtheriae were recovered from four cases (cases 1 to 4) with epidermolysis bullosa attending the clinic. Two further isolates were subsequently recovered from case 4, >18 months later, and from two household contacts (cases 5 and 6) after a further 18 months and 3.5 years, respectively. All eight strains were NTTB C. diphtheriae biovar mitis, belonged to the same sequence type (ST-336) with the same deletion in tox . Phylogenetic analysis showed relatively high diversity between the eight strains with 7-199 SNP and 3-109 cgMLST loci differences between them. The number of SNPs between the three isolates from case 4 and two household contacts (cases 5 and 6) was 44-70 with 28-38 cgMLST loci differences. Conclusions. We report a cluster of NTTB C. diphtheriae cases in a skin clinic and evidence of onward household transmission. We conclude the deletion in the tox was responsible for the non-expression of DT. There was no evidence of reversion to DT expression over the 6.5 year period studied. These data informed revision to guidance in the management of NTTB cases and their contacts in the UK.

Memories of life episodes are the heart of individual stories. However, modelling episodic memory is a major challenge in both humans and animals when considering all its characteristics. As a consequence, the mechanisms that underlie the storage of old nontraumatic episodic memories remain enigmatic. Here, using a new task in rodents that models human episodic memory including odour/place/context components and applying advances behavioural and computational analyses, we show that rats form and recollect integrated remote episodic memories of two occasionally encountered complex episodes occurring in their daily life. Similar to humans, the information content and accuracy of memories vary across individuals and depend on the emotional relationship with odours experienced during the very first episode. We used cellular brain imaging and functional connectivity analyses, to find out the engrams of remote episodic memories for the first time. Activated brain networks completely reflect the nature and content of episodic memories, with a larger cortico-hippocampal network when the recollection is complete and with an emotional brain network related to odours that is critical in maintaining accurate and vivid memories. The engrams of remote episodic memories remain highly dynamic since synaptic plasticity processes occur during recall related to memory updates and reinforcement., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction . The New Delhi metallo-β-lactamase (NDM) variant NDM-5 was first described in 2011 in an isolate of Escherichia coli . We noted that a high proportion of isolates of E. coli positive for bla NDM carbapenemase genes submitted to the UK Health Security Agency (formerly Public Health England) between 2019 and mid-2021 carried the bla NDM-5 allele, with many co-harbouring rmtB , rendering them highly resistant to aminoglycosides as well as to most β-lactams. Hypothesis/Gap Statement . This observation suggested that a common plasmid may be circulating. Aim . To compare these isolates and describe the plasmids carrying these resistance elements. Methodology . All isolates were sequenced on an Illumina platform, with five also subjected to long-read nanopore sequencing to provide complete assemblies. The locations of bla NDM-5 , rmtB and other associated genetic elements were identified. Susceptibility testing to a wide range of antibiotics was carried out on representative isolates. Results . The 34 isolates co-harbouring bla NDM-5 and rmtB were from 14 hospital groups and six different regions across England and consisted of 11 distinct sequence types. All carried IncF plasmids. Assembly of the NDM plasmids in five isolates revealed that they carried rmtB and bla NDM-5 in an IncF conjugative plasmid ranging in size from 85.5 to 161 kb. All carried a highly conserved region, previously described in E. coli plasmid pHC105-NDM, that included bla TEM-1B and rmtB followed by sequence bounded by two IS 26 elements containing ΔIS Aba125 , bla NDM-5 , ble , trpF and tat followed by IS CR1 and an integron with sul1 , aadA2 and dfrA12 cassettes. This arrangement has been described in isolates from other countries and continents, suggesting that such plasmids are widely distributed, at least in E. coli , with similar plasmids also found in Klebsiella pneumoniae . Tested isolates were resistant to most antibiotics except colistin, fosfomycin and tigecycline. Conclusion . These observations suggest that conjugative plasmids carrying a highly conserved resistance gene segment have become widespread in England and elsewhere. This study highlights the value of routine whole-genome sequencing in identifying genetic elements responsible for resistance dissemination.

Introduction. Increasing numbers of carbapenemase-producing Enterobacterales (CPE), which can be challenging to treat, have been referred to the national reference laboratory in England since the early 2000s. Gap Statement/Aim. Previous studies on CPE in the UK have focussed on localized outbreaks. We applied whole-genome sequencing (WGS) to isolates referred to the national reference laboratory over 30 months to inform our understanding of CPE epidemiology in England. Methodology. The first confirmed CPE from each new patient referred by an English diagnostic laboratory between 1 January 2014 and 30 June 2016 was sequenced on an Illumina HiSeq 2500. Multiple isolates from the same patient were included from either different species or the same species with different carbapenemase genes. The data were analysed using an in-house bioinformatics pipeline that determines species identification, multi-locus sequence typing (MLST) profile and antimicrobial resistance gene content. Results. A total of 2658 non-duplicate CPE were sequenced amongst which three host organisms belonging to diverse sequence types (STs) predominated: Klebsiella pneumoniae (1380/2658, 51.9 %; 177 STs), Escherichia coli (723/2658, 27.2 %; 133 STs) and Enterobacter cloacae (294/2658, 11.1 %; 88 STs). Thirty different carbapenemase gene variants were identified, although bla OXA-48-like (1122/2658, 42.2%), bla NDM (692/2658, 26.0 %), bla KPC (571/2658, 21.5 %), bla VIM (100/2658, 3.8 %) and bla IMP (33/2658, 1.2 %) predominated. ST/carbapenemase gene pairings represented widely distributed high-risk clones or clusters at a regional or hospital level. Conclusion. CPE referred to the national reference laboratory are diverse, suggesting multiple introductions to England and a role for horizontal transfer of carbapenemase genes in English CPE epidemiology.

Transferable linezolid resistance due to optrA , poxtA , cfr and cfr -like genes is increasingly detected in enterococci associated with animals and humans globally. We aimed to characterize the genetic environment of optrA in linezolid-resistant Enterococcus faecalis isolates from Scotland. Six linezolid-resistant E. faecalis isolated from urogenital samples were confirmed to carry the optrA gene by PCR. Short read (Illumina) sequencing showed the isolates were genetically distinct (>13900 core SNPs) and belonged to different MLST sequence types. Plasmid contents were examined using hybrid assembly of short and long read (Oxford Nanopore MinION) sequencing technologies. The optrA gene was located on distinct plasmids in each isolate, suggesting that transfer of a single plasmid did not contribute to optrA dissemination in this collection. pTM6294-2, BX5936-1 and pWE0438-1 were similar to optrA -positive plasmids from China and Japan, while the remaining three plasmids had limited similarity to other published examples. We identified the novel Tn 6993 transposon in pWE0254-1 carrying linezolid ( optrA ), macrolide ( ermB ) and spectinomycin [ANT(9)-Ia] resistance genes. OptrA amino acid sequences differed by 0-20 residues. We report multiple variants of optrA on distinct plasmids in diverse strains of E. faecalis . It is important to identify the selection pressures driving the emergence and maintenance of resistance against linezolid to retain the clinical utility of this antibiotic.