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The cytochrome P450 (CYP) enzyme family catalyses the metabolism of approximately 80% of all medications.1, 2 Many genes encoding the CYP enzymes exhibit high levels of polymorphism that affect their expression and activity. The most frequent and clinically important variations exist within the genes CYP2D6, CYP2C19 and CYP2C9.1 CYP2D6, the most extensively studied drug-metabolizing enzyme, has over 100 allelic variants and is responsible for metabolizing about 25% of all marketed medications.1, 3 CYP2C19 and CYP2C9 are collectively responsible for metabolizing about 20% of medications. It is estimated that 74%–97% of Caucasian individuals possess at least one genetic variation in the CYP gene, potentially affecting metabolism for about one quarter of all prescribed medications.4 Testing for this genetic variation can help identify individuals for whom medication safety and efficacy can be improved through dose adjustment.1 Pharmacogenetic (PGx) testing assesses genetic variation by identifying a patient's genotype and assigning a predicted phenotype. The predicted phenotype of an inherited allele can be classified as loss of function, decreased function, normal function or increased function.3 Numerous PGx tests have been developed for both public and private use. The evidence for whether these tests actually improve treatment outcomes is controversial, but a large implementation study recently showed that pre-emptive PGx testing may reduce the incidence of adverse reactions.5 PGx tests are normally based on genotyping panels with predefined alleles, but variations in these panels between PGx providers and in the approach for genotype-to-phenotype translation can result in conflicting recommendations.6, 7 Current guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) recommend classifying phenotypes into four, five and three categories for CYP2D6, CYP2C19 and CYP2C9, respectively.8 Despite these recommendations, a recent st

By consuming ammonium and nitrite, anammox bacteria form an important functional guild in nitrogen cycling in many environments, including marine sediments. However, their distribution and impact on the important substrate nitrite has not been well characterized. Here we combined biogeochemical, microbiological, and genomic approaches to study anammox bacteria and other nitrogen cycling groups in two sediment cores retrieved from the Arctic Mid-Ocean Ridge (AMOR). We observed nitrite accumulation in these cores, a phenomenon also recorded at 28 other marine sediment sites and in analogous aquatic environments. The nitrite maximum coincides with reduced abundance of anammox bacteria. Anammox bacterial abundances were at least one order of magnitude higher than those of nitrite reducers and the anammox abundance maxima were detected in the layers above and below the nitrite maximum. Nitrite accumulation in the two AMOR cores co-occurs with a niche partitioning between two anammox bacterial families (Candidatus Bathyanammoxibiaceae and Candidatus Scalinduaceae), likely dependent on ammonium availability. Through reconstructing and comparing the dominant anammox genomes (Ca. Bathyanammoxibius amoris and Ca. Scalindua sediminis), we revealed that Ca. B. amoris has fewer high-affinity ammonium transporters than Ca. S. sediminis and lacks the capacity to access alternative substrates and/or energy sources such as urea and cyanate. These features may restrict Ca. Bathyanammoxibiaceae to conditions of higher ammonium concentrations. These findings improve our understanding about nitrogen cycling in marine sediments by revealing coincident nitrite accumulation and niche partitioning of anammox bacteria.

The cytochrome P450 (CYP) enzyme family catalyses the metabolism of approximately 80% of all medications.1, 2 Many genes encoding the CYP enzymes exhibit high levels of polymorphism that affect their expression and activity. The most frequent and clinically important variations exist within the genes CYP2D6, CYP2C19 and CYP2C9.1 CYP2D6, the most extensively studied drug-metabolizing enzyme, has over 100 allelic variants and is responsible for metabolizing about 25% of all marketed medications.1, 3 CYP2C19 and CYP2C9 are collectively responsible for metabolizing about 20% of medications. It is estimated that 74%–97% of Caucasian individuals possess at least one genetic variation in the CYP gene, potentially affecting metabolism for about one quarter of all prescribed medications.4 Testing for this genetic variation can help identify individuals for whom medication safety and efficacy can be improved through dose adjustment.1 Pharmacogenetic (PGx) testing assesses genetic variation by identifying a patient's genotype and assigning a predicted phenotype. The predicted phenotype of an inherited allele can be classified as loss of function, decreased function, normal function or increased function.3 Numerous PGx tests have been developed for both public and private use. The evidence for whether these tests actually improve treatment outcomes is controversial, but a large implementation study recently showed that pre-emptive PGx testing may reduce the incidence of adverse reactions.5 PGx tests are normally based on genotyping panels with predefined alleles, but variations in these panels between PGx providers and in the approach for genotype-to-phenotype translation can result in conflicting recommendations.6, 7 Current guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) recommend classifying phenotypes into four, five and three categories for CYP2D6, CYP2C19 and CYP2C9, respectively.8 Despite these recommendations, a recent st

Introduction: Shallow hydrothermal systems share many characteristics with their deep-sea counterparts, but their accessibility facilitates their study. One of the most studied shallow hydrothermal vent fields lies at Paleochori Bay off the coast of Milos in the Aegean Sea (Greece). It has been studied through extensive mapping and its physical and chemical processes have been characterized over the past decades. However, a thorough description of the microbial communities inhabiting the bay is still missing. Methods: We present the first in-depth characterization of the prokaryotic communities of Paleochori Bay by sampling eight different seafloor types that are distributed along the entire gradient of hydrothermal influence. We used deep sequencing of the 16S rRNA marker gene and complemented the analysis with qPCR quantification of the 16S rRNA gene and several functional genes to gain insights into the metabolic potential of the communities. Results: We found that the microbiome of the bay is strongly influenced by the hydrothermal venting, with a succession of various groups dominating the sediments from the coldest to the warmest zones. Prokaryotic diversity and abundance decrease with increasing temperature, and thermophilic archaea overtake the community. Discussion: Relevant geochemical cycles of the Bay are discussed. This study expands our limited understanding of subsurface microbial communities in acidic shallow-sea hydrothermal systems and the contribution of their microbial activity to biogeochemical cycling., Funding for the Saganaki dataset and JPA and G-SL was provided by NSF grants OIA-0939564 to the Center for Dark Energy Biosphere Investigations (C-DEBI). The CarDHynAl project was partially funded by INSU-CNRS Tellus and Syster Projects to JEs (2016) and J-EM (2018), and with partial support by RAMONES, funded by the European Union’s Horizon 2020 Research and Innovation Program, under grant agreement number 101017808 (to JEs and PN). The laboratory work was supported by the Trond Mohn Foundation and the University of Bergen through the Centre for Deep Sea research (grant TMS2020TMT13). VP-G and JEg are supported by the Spanish Ministry of Science and Innovation and the European Regional Development Fund [grant numbers PID2021- 125380OB-I00 and PID2021-123833OB-I00 (MCIN/AEI/ FEDER)]., Peer Reviewed, Postprint (published version)

Background: Infection in the oviduct (salpingitis) is the most common bacterial infection in egg laying hens and is mainly caused by Escherichia coli. The disease is responsible for decreased animal welfare, considerable economic loss as well as a risk of horizontal and vertical transmission of pathogenic E. coli. The outcome of salpingitis may be either acute or chronic. It has not yet been clarified whether the pathological manifestation is a result of the characteristics of the E. coli or whether the manifestation is associated with host factors such as host immunity. Results: From the core- A nd accessory genome analysis and comparison of 62 E. coli no genetic markers were found to be associated to either acute or chronic infection. Twenty of the 62 genomes harboured at least one antimicrobial resistance gene with resistance against sulfonamides being the most common. The increased serum survival and iron chelating genes iss and iroN were highly prevalent in genomes from both acute and chronic salpingitis. Conclusion: Our analysis revealed that no genetic markers could differentiate the E. coli isolated from acute versus chronic salpingitis in egg laying hens. The difference in pathological outcome may be related to other factors such as immunological status, genetics and health of the host. These data indicate that salpingitis is another manifestation of colibacillosis.

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The bacterial phylum Chlamydiae is so far composed of obligate symbionts of eukaryotic hosts. Well known for Chlamydiaceae, pathogens of humans and other animals, Chlamydiae also include so-called environmental lineages that primarily infect microbial eukaryotes. Environmental surveys indicate that Chlamydiae are found in a wider range of environments than anticipated previously. However, the vast majority of this chlamydial diversity has been underexplored, biasing our current understanding of their biology, ecological importance, and evolution. Here, we report that previously undetected and active chlamydial lineages dominate microbial communities in deep anoxic marine sediments taken from the Arctic Mid-Ocean Ridge. Reaching relative abundances of up to 43% of the bacterial community, and a maximum diversity of 163 different species-level taxonomic units, these Chlamydiae represent important community members. Using genome-resolved metagenomics, we reconstructed 24 draft chlamydial genomes, expanding by over a third the known genomic diversity in this phylum. Phylogenomic analyses revealed several novel clades across the phylum, including a previously unknown sister lineage of the Chlamydiaceae, providing new insights into the origin of pathogenicity in this family. We were unable to identify putative eukaryotic hosts for these marine sediment chlamydiae, despite identifying genomic features that may be indicative of host-association. The high abundance and genomic diversity of Chlamydiae in these anoxic marine sediments indicate that some members could play an important, and thus far overlooked, ecological role in such environments and may indicate alternate lifestyle strategies.

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MicroRNAs are small regulatory RNAs that are deregulated in a wide variety of human cancers, including different types of B-cell lymphoma. Nevertheless, the feasibility of circulating microRNA for early diagnosis of B-cell lymphoma has not been established. To address the possibility of detecting specific circulating microRNAs years before a B-cell lymphoma is diagnosed, we studied the plasma expression of microRNA first in pre-treatment samples from patients with diffuse large B-cell lymphoma and subsequently in repository samples from blood donors who later developed B-cell lymphomas. In addition, we studied the microRNA expression in the diagnostic lymphoma biopsy. The most strongly induced (miR-326) and suppressed (miR-375) plasma microRNA at diagnosis, when compared with healthy blood donors, were also substantially up- or down-regulated in plasma repository samples taken from several months to up to two years before the blood donors were diagnosed with B-cell lymphoma. Importantly, at these time points the donors had no signs of disease and felt healthy enough to donate blood. In conclusion, this first study of plasma microRNA profiles from apparently healthy individuals, taken several years before B-cell lymphoma diagnosis, suggests that plasma microRNA profiles may be predictive of lymphoma development.

Background: Infection in the oviduct (salpingitis) is the most common bacterial infection in egg laying hens and is mainly caused by Escherichia coli. The disease is responsible for decreased animal welfare, considerable economic loss as well as a risk of horizontal and vertical transmission of pathogenic E. coli. The outcome of salpingitis may be either acute or chronic. It has not yet been clarified whether the pathological manifestation is a result of the characteristics of the E. coli or whether the manifestation is associated with host factors such as host immunity. Results: From the core- A nd accessory genome analysis and comparison of 62 E. coli no genetic markers were found to be associated to either acute or chronic infection. Twenty of the 62 genomes harboured at least one antimicrobial resistance gene with resistance against sulfonamides being the most common. The increased serum survival and iron chelating genes iss and iroN were highly prevalent in genomes from both acute and chronic salpingitis. Conclusion: Our analysis revealed that no genetic markers could differentiate the E. coli isolated from acute versus chronic salpingitis in egg laying hens. The difference in pathological outcome may be related to other factors such as immunological status, genetics and health of the host. These data indicate that salpingitis is another manifestation of colibacillosis.

Background: Infection in the oviduct (salpingitis) is the most common bacterial infection in egg laying hens and is mainly caused by Escherichia coli. The disease is responsible for decreased animal welfare, considerable economic loss as well as a risk of horizontal and vertical transmission of pathogenic E. coli. The outcome of salpingitis may be either acute or chronic. It has not yet been clarified whether the pathological manifestation is a result of the characteristics of the E. coli or whether the manifestation is associated with host factors such as host immunity. Results: From the core- A nd accessory genome analysis and comparison of 62 E. coli no genetic markers were found to be associated to either acute or chronic infection. Twenty of the 62 genomes harboured at least one antimicrobial resistance gene with resistance against sulfonamides being the most common. The increased serum survival and iron chelating genes iss and iroN were highly prevalent in genomes from both acute and chronic salpingitis. Conclusion: Our analysis revealed that no genetic markers could differentiate the E. coli isolated from acute versus chronic salpingitis in egg laying hens. The difference in pathological outcome may be related to other factors such as immunological status, genetics and health of the host. These data indicate that salpingitis is another manifestation of colibacillosis.

The origin of eukaryotes is a major open question in evolutionary biology. Multiple hypotheses posit that eukaryotes likely evolved from a syntrophic relationship between an archaeon and an alphaproteobacterium based on H2 exchange. However, there are no strong indications that modern eukaryotic H2 metabolism originated from archaea or alphaproteobacteria. Here, we present evidence for the origin of H2 metabolism genes in eukaryotes from an ancestor of the Anoxychlamydiales-a group of anaerobic chlamydiae, newly described here, from marine sediments. Among Chlamydiae, these bacteria uniquely encode genes for H2 metabolism and other anaerobiosis-associated pathways. Phylogenetic analyses of several components of H2 metabolism reveal that Anoxychlamydiales homologs are the closest relatives to eukaryotic sequences. We propose that an ancestor of the Anoxychlamydiales contributed these key genes during the evolution of eukaryotes, supporting a mosaic evolutionary origin of eukaryotic metabolism.

MicroRNAs are small regulatory RNAs that are deregulated in a wide variety of human cancers, including different types of B-cell lymphoma. Nevertheless, the feasibility of circulating microRNA for early diagnosis of B-cell lymphoma has not been established. To address the possibility of detecting specific circulating microRNAs years before a B-cell lymphoma is diagnosed, we studied the plasma expression of microRNA first in pre-treatment samples from patients with diffuse large B-cell lymphoma and subsequently in repository samples from blood donors who later developed B-cell lymphomas. In addition, we studied the microRNA expression in the diagnostic lymphoma biopsy. The most strongly induced (miR-326) and suppressed (miR-375) plasma microRNA at diagnosis, when compared with healthy blood donors, were also substantially up- or down-regulated in plasma repository samples taken from several months to up to two years before the blood donors were diagnosed with B-cell lymphoma. Importantly, at these time points the donors had no signs of disease and felt healthy enough to donate blood. In conclusion, this first study of plasma microRNA profiles from apparently healthy individuals, taken several years before B-cell lymphoma diagnosis, suggests that plasma microRNA profiles may be predictive of lymphoma development.

The bacterial phylum Chlamydiae is so far composed of obligate symbionts of eukaryotic hosts. Well known for Chlamydiaceae, pathogens of humans and other animals, Chlamydiae also include so-called environmental lineages that primarily infect microbial eukaryotes. Environmental surveys indicate that Chlamydiae are found in a wider range of environments than anticipated previously. However, the vast majority of this chlamydial diversity has been underexplored, biasing our current understanding of their biology, ecological importance, and evolution. Here, we report that previously undetected and active chlamydial lineages dominate microbial communities in deep anoxic marine sediments taken from the Arctic Mid-Ocean Ridge. Reaching relative abundances of up to 43% of the bacterial community, and a maximum diversity of 163 different species-level taxonomic units, these Chlamydiae represent important community members. Using genome-resolved metagenomics, we reconstructed 24 draft chlamydial genomes, expanding by over a third the known genomic diversity in this phylum. Phylogenomic analyses revealed several novel clades across the phylum, including a previously unknown sister lineage of the Chlamydiaceae, providing new insights into the origin of pathogenicity in this family. We were unable to identify putative eukaryotic hosts for these marine sediment chlamydiae, despite identifying genomic features that may be indicative of host-association. The high abundance and genomic diversity of Chlamydiae in these anoxic marine sediments indicate that some members could play an important, and thus far overlooked, ecological role in such environments and may indicate alternate lifestyle strategies. Dharamshi et al. find abundant, diverse, and active Chlamydiae in deep anoxic marine sediments. Using metagenomics, chlamydial genomes are obtained that form several new clades. Analyses of these genomes provide new insights into the evolution and host association of the Chlamydiae phyl

Avian-pathogenic Escherichia coli (APEC) is a subgroup of extraintestinal pathogenic E. coli (ExPEC) presumed to be zoonotic and to represent an external reservoir for extraintestinal infections in humans, including uropathogenic E. coli (UPEC) causing urinary tract infections. Comparative genomics has previously been applied to investigate whether APEC and human ExPEC are distinct entities. Even so, whole-genome-based studies are limited, and large-scale comparisons focused on single sequence types (STs) are not available yet. In this study, comparative genomic analysis was performed on 323 APEC and human ExPEC genomes belonging to sequence type 95 (ST95) to investigate whether APEC and human ExPEC are distinct entities. Our study showed that APEC of ST95 did not constitute a unique ExPEC branch and was genetically diverse. A large genetic overlap between APEC and certain human ExPEC was observed, with APEC located on multiple branches together with closely related human ExPEC, including nearly identical APEC and human ExPEC. These results illustrate that certain ExPEC clones may indeed have the potential to cause infection in both poultry and humans. Previously described ExPEC-associated genes were found to be encoded on ColV plasmids. These virulence-associated plasmids seem to be crucial for ExPEC strains to cause avian colibacillosis and are strongly associated with strains of the mixed APEC/ human ExPEC clusters. The phylogenetic analysis revealed two distinct branches consisting of exclusively closely related human ExPEC which did not carry the virulence-associated plasmids, emphasizing a lower avian virulence potential of human ExPEC in relation to an avian host.

Background: Antimicrobial helper-compounds may reverse antimicrobial resistance. Sertraline, a antidepressant drug, has been suggested as a tetracycline helper-compound. Tetracycline is the preferred antimicrobial for treatment of enteric diseases in pigs. This study is the first to evaluate the potency of sertraline as a tetracycline adjuvant in pigs. Methods: Forty-eight nursery pigs were divided into four treatment groups: Tetracycline, sertraline, tetracycline/sertraline or un-medicated control. Fecal and ileal samples were obtained before treatment, 48 h and nine days after five days of treatment, respectively. Colony forming units (CFU) of tetracycline resistant coliforms in each sample (ileal or fecal) and CFU of an orally inoculated tetracycline-resistant strain of Escherichia coli were determined at each sampling point. The microbiome of fecal and ileal and samples was analyzed by sequencing of the 16S V3-V4 region. Results: The results did not provide evidence that sertraline in combination with tetracycline has any impact on tetracycline resistant bacteria in either fecal or ileum samples, while in the tetracycline treated group of pigs, an increase in the prevalence of a tetracycline resistant indicator strain of Escherichia coli shortly after ended five-day treatment was observed. The ileal samples obtained shortly after ended treatment showed treatment-associated changes in the composition of the microbiota in the groups of pigs treated with tetracycline (+/-) sertraline. While tetracycline treatment increased the abundance in the reads of E. coli, sertraline/tetracycline treatment led to increased abundances of Streptococcus spp. and decreased abundances of Lactobacillus spp. However, all observed differences (on CFU counts and microbiota composition) between groups shortly after treatment had diminished in less than two weeks after last treatment day. Conclusions: Sertraline (+/-) tetracycline treatment did not reduce the long-term level of tetrac

Background: Antimicrobial helper-compounds may reverse antimicrobial resistance. Sertraline, a antidepressant drug, has been suggested as a tetracycline helper-compound. Tetracycline is the preferred antimicrobial for treatment of enteric diseases in pigs. This study is the first to evaluate the potency of sertraline as a tetracycline adjuvant in pigs. Methods: Forty-eight nursery pigs were divided into four treatment groups: Tetracycline, sertraline, tetracycline/sertraline or un-medicated control. Fecal and ileal samples were obtained before treatment, 48 h and nine days after five days of treatment, respectively. Colony forming units (CFU) of tetracycline resistant coliforms in each sample (ileal or fecal) and CFU of an orally inoculated tetracycline-resistant strain of Escherichia coli were determined at each sampling point. The microbiome of fecal and ileal and samples was analyzed by sequencing of the 16S V3-V4 region. Results: The results did not provide evidence that sertraline in combination with tetracycline has any impact on tetracycline resistant bacteria in either fecal or ileum samples, while in the tetracycline treated group of pigs, an increase in the prevalence of a tetracycline resistant indicator strain of Escherichia coli shortly after ended five-day treatment was observed. The ileal samples obtained shortly after ended treatment showed treatment-associated changes in the composition of the microbiota in the groups of pigs treated with tetracycline (+/-) sertraline. While tetracycline treatment increased the abundance in the reads of E. coli, sertraline/tetracycline treatment led to increased abundances of Streptococcus spp. and decreased abundances of Lactobacillus spp. However, all observed differences (on CFU counts and microbiota composition) between groups shortly after treatment had diminished in less than two weeks after last treatment day. Conclusions: Sertraline (+/-) tetracycline treatment did not reduce the long-term level of tetrac

Avian-pathogenic Escherichia coli (APEC) is a subgroup of extraintestinal pathogenic E. coli (ExPEC) presumed to be zoonotic and to represent an external reservoir for extraintestinal infections in humans, including uropathogenic E. coli (UPEC) causing urinary tract infections. Comparative genomics has previously been applied to investigate whether APEC and human ExPEC are distinct entities. Even so, whole-genome-based studies are limited, and large-scale comparisons focused on single sequence types (STs) are not available yet. In this study, comparative genomic analysis was performed on 323 APEC and human ExPEC genomes belonging to sequence type 95 (ST95) to investigate whether APEC and human ExPEC are distinct entities. Our study showed that APEC of ST95 did not constitute a unique ExPEC branch and was genetically diverse. A large genetic overlap between APEC and certain human ExPEC was observed, with APEC located on multiple branches together with closely related human ExPEC, including nearly identical APEC and human ExPEC. These results illustrate that certain ExPEC clones may indeed have the potential to cause infection in both poultry and humans. Previously described ExPEC-associated genes were found to be encoded on ColV plasmids. These virulence-associated plasmids seem to be crucial for ExPEC strains to cause avian colibacillosis and are strongly associated with strains of the mixed APEC/ human ExPEC clusters. The phylogenetic analysis revealed two distinct branches consisting of exclusively closely related human ExPEC which did not carry the virulence-associated plasmids, emphasizing a lower avian virulence potential of human ExPEC in relation to an avian host.

Avian-pathogenic Escherichia coli (APEC) is a subgroup of extraintestinal pathogenic E.coli (ExPEC) presumed to be zoonotic and to represent an external reservoir for extraintestinal infections in humans, including uropathogenic E. coli (UPEC) causing urinary tract infections. Comparative genomics has previously been applied to investigate whether APEC and human ExPEC are distinct entities. Even so, whole-genome-based studies are limited, and large-scale comparisons focused on single sequence types (STs) are not available yet. In this study, comparative genomic analysis was performed on 323 APEC and human ExPEC genomes belonging to sequence type 95 (ST95) to investigate whether APEC and human ExPEC are distinct entities. Our study showed that APEC of ST95 did not constitute a unique ExPEC branch and was genetically diverse. A large genetic overlap between APEC and certain human ExPEC was observed, with APEC located on multiple branches together with closely related human ExPEC, including nearly identical APEC and human ExPEC. These results illustrate that certain ExPEC clones may indeed have the potential to cause infection in both poultry and humans. Previously described ExPEC-associated genes were found to be encoded on ColV plasmids. These virulence-associated plasmids seem to be crucial for ExPEC strains to cause avian colibacillosis and are strongly associated with strains of the mixed APEC/human ExPEC clusters. The phylogenetic analysis revealed two distinct branches consisting of exclusively closely related human ExPEC which did not carry the virulence-associated plasmids, emphasizing a lower avian virulence potential of human ExPEC in relation to an avian host.IMPORTANCE APEC causes a range of infections in poultry, collectively called colibacillosis, and is the leading cause of mortality and is associated with major economic significance in the poultry industry. A growing number of studies have suggested APEC as an external reservoir of human ExPEC, incl

The aim of the study was to investigate cellulitis caused by Escherichia coli which has been responsible for economic and welfare problems in Danish broiler production between 2014 and 2016. The study included 13 flocks with unusually high condemnation rates due to cellulitis during a period of approximately one year. From six flocks, 126 condemned carcasses were collected at a Danish slaughterhouse. Further 272 broilers dead on their own were collected on nine broiler farms from flocks with increased mortality and cellulitis (2 farms included both birds from the rearing period and broilers subsequently condemned). All broilers were subjected to post mortem investigation including bacteriology and 247 E. coli isolates were obtained in pure culture from typical lesions of cellulitis. Two-hundred-thirty six E. coli isolates were investigated by pulsed field gel electrophoresis for clonality and 21 selected strains representing major clones were subsequently multi locus sequence typed allowing comparison to sequence types (ST) in the databases. One dominating PFGE type (A) was found to cause cellulitis on all 13 flocks (67% of all isolates). The clone belonged to ST117, which is well described as a pathogen in poultry, and was the primary agent responsible for cellulitis. Whole genome sequencing of eight E. coli isolates confirmed the close genetic relationship between isolates from the outbreaks and showed the presence of genes predicted to encode for the autotransporter proteins aatA, pic and upaG, reported to be of importance for adhesion of E. coli to eukaryotic cells.

Extracellular DNA has been reported to comprise a large fraction of total DNA in near-seafloor sediment. However, the potential effect of extracellular DNA, arising from dead or moribund cells, on sequencing surveys is a critical concern that has largely not been addressed for marine sedimentary habitats. To address this concern, we interrogated freshly collected Arctic and Pacific sediment for extracellular 16S rRNA genes using the photoactive DNA-binding dye Propidium Monoazide. Significant differences between relative abundances of total (intracellular + extracellular) Bacterial 16S rRNA genes and relative abundances of intracellular Bacterial 16S rRNA genes are only detected in three of twelve shallow [10 cm below seafloor (cmbsf)] samples. Relative abundances of total Bacterial 16S rRNA genes are statistically indistinguishable from relative abundances of intracellular Bacterial 16S rRNA genes in all interrogated samples from depths greater than 10 cmbsf. 16S rRNA gene sequencing shows that even where significantly higher abundances of extracellular genes are detected, they have little or no influence on prokaryote community composition. Taxon-level analyses suggest that extracellular DNA, arising from in situ death, may be sourced from different organisms in sediment of different ages. However, the overall effect of extracellular genes on sequencing surveys of marine sedimentary prokaryotes is minimal.

Escherichia coli causing infection outside the gastrointestinal system are referred to as extra-intestinal pathogenic E. coli. Avian pathogenic E. coli is a subgroup of extra-intestinal pathogenic E. coli and infections due to avian pathogenic E. coli have major impact on poultry production economy and welfare worldwide. An almost defining characteristic of avian pathogenic E. coli is the carriage of plasmids, which may encode virulence factors and antibiotic resistance determinates. For the same reason, plasmids of avian pathogenic E. coli have been intensively studied. However, genes encoded by the chromosome may also be important for disease manifestation and antimicrobial resistance. For the E. coli strain APEC_O2 the plasmids have been sequenced and analyzed in several studies, and E. coli APEC_O2 may therefore serve as a reference strain in future studies. Here we describe the chromosomal features of E. coli APEC_O2. E. coli APEC_O2 is a sequence type ST135, has a chromosome of 4,908,820 bp (plasmid removed), comprising 4672 protein-coding genes, 110 RNA genes, and 156 pseudogenes, with an average G + C content of 50.69%. We identified 82 insertion sequences as well as 4672 protein coding sequences, 12 predicated genomic islands, three prophage-related sequences, and two clustered regularly interspaced short palindromic repeats regions on the chromosome, suggesting the possible occurrence of horizontal gene transfer in this strain. The wildtype strain of E. coli APEC_O2 is resistant towards multiple antimicrobials, however, no (complete) antibiotic resistance genes were present on the chromosome, but a number of genes associated with extra-intestinal disease were identified. Together, the information provided here on E. coli APEC_O2 will assist in future studies of avian pathogenic E. coli strains, in particular regarding strain of E. coli APEC_O2, and aid in the general understanding of the pathogenesis of avian pathogenic E. coli.

Escherichia coli causing infection outside the gastrointestinal system are referred to as extra-intestinal pathogenic E. coli. Avian pathogenic E. coli is a subgroup of extra-intestinal pathogenic E. coli and infections due to avian pathogenic E. coli have major impact on poultry production economy and welfare worldwide. An almost defining characteristic of avian pathogenic E. coli is the carriage of plasmids, which may encode virulence factors and antibiotic resistance determinates. For the same reason, plasmids of avian pathogenic E. coli have been intensively studied. However, genes encoded by the chromosome may also be important for disease manifestation and antimicrobial resistance. For the E. coli strain APEC_O2 the plasmids have been sequenced and analyzed in several studies, and E. coli APEC_O2 may therefore serve as a reference strain in future studies. Here we describe the chromosomal features of E. coli APEC_O2. E. coli APEC_O2 is a sequence type ST135, has a chromosome of 4,908,820 bp (plasmid removed), comprising 4672 protein-coding genes, 110 RNA genes, and 156 pseudogenes, with an average G + C content of 50.69%. We identified 82 insertion sequences as well as 4672 protein coding sequences, 12 predicated genomic islands, three prophage-related sequences, and two clustered regularly interspaced short palindromic repeats regions on the chromosome, suggesting the possible occurrence of horizontal gene transfer in this strain. The wildtype strain of E. coli APEC_O2 is resistant towards multiple antimicrobials, however, no (complete) antibiotic resistance genes were present on the chromosome, but a number of genes associated with extra-intestinal disease were identified. Together, the information provided here on E. coli APEC_O2 will assist in future studies of avian pathogenic E. coli strains, in particular regarding strain of E. coli APEC_O2, and aid in the general understanding of the pathogenesis of avian pathogenic E. coli.

AIM: Diarrhoea is very common in children attending day care centres. The aim of this study was to examine certain predisposing risk factors for an association with diarrhoea, including foreign travel, treatment with antibiotics, having household pets, infant colic, bottle feeding, using a pacifier and low birth weight.METHODS: A dynamic one-year follow-up cohort study comprising 179 children from 36 day care centres was conducted from September 2009 to July 2013 in Copenhagen, Denmark. Questionnaires were sent to the children's parents or legal guardians every two months for a year, requesting information on gastrointestinal symptoms and exposure. A logistic regression was performed to identify the odds ratios of different risk factors for diarrhoea.RESULTS: The odds ratios for diarrhoea were 1.97 (0.93-4.20) for children with a history of infant colic, 1.91 (0.90-4.04) for low birth weight children and 1.45 (0.74-2.82) for children who had used antibiotics. Having a pet in the household had a possible protective effect towards diarrhoeal events, with an odds ratio of 0.47 (0.20-1.09).CONCLUSION: A history of infant colic, low birth weight, and to a lesser extent antibiotic use, increased the risk of diarrhoea in Danish children in day care centres This article is protected by copyright. All rights reserved.

What are Socrates ’ aims and strategies in the Cratylus? Does Socrates seek to convince his interlocutors that there is a source of linguistic correctness, which goes beyond human agreement, and which really determines whether the name of something is the correct name? Or does Socrates seek to achieve the opposite? What strategies does Socrates use, and why? These questions are central to my thesis, which offer s a new interpretation of Plato’s Cratylus . In the thesis I argue that Socrates really does seek to convince his interlocutors that there is a “natural correctness of names” , but that he does so in a very special way, which is closely linked to the specific characters and views of his interlocutors.

What are Socrates ’ aims and strategies in the Cratylus? Does Socrates seek to convince his interlocutors that there is a source of linguistic correctness, which goes beyond human agreement, and which really determines whether the name of something is the correct name? Or does Socrates seek to achieve the opposite? What strategies does Socrates use, and why? These questions are central to my thesis, which offer s a new interpretation of Plato’s Cratylus . In the thesis I argue that Socrates really does seek to convince his interlocutors that there is a “natural correctness of names” , but that he does so in a very special way, which is closely linked to the specific characters and views of his interlocutors.

Indledning til Roman Jakobson: >>To aspekter af sproget og to typer afatisk forstyrrelse

I.A. Richards, M. Black, Lakoff & Johnson

Wnt signaling is often constitutively active in colorectal cancer cells. The expression of the intestinal specific transcription factor CDX2 is found to be transiently decreased in invasive cells at the tumor/stroma interface. A recent ChIP-Seq study has indicated that several Wnt signaling-related genes are regulated by CDX2. The aim was to investigate the role of decreased CDX2 level on the expression of APC, AXIN2 and GSK3β in migrating colon cancer cells at the invasive front. CDX2-bound promoter and enhancer regions from APC, AXIN2 and GSK3β were analyzed for gene regulatory activity and the expression pattern of APC and GSK3β at the invasive front was evaluated by immunohistochemical procedures. Transfection of intestinal and non-intestinal cell lines demonstrated that CDX2 activated APC and AXIN2 promoter activities via intestinal cell-specific enhancer elements. Suppressed CDX2 expression was associated with endogenous downregulation of APC and AXIN2 expression in Caco-2 cells but did not affect GSK3β expression. Furthermore, elevated levels of nuclear β-catenin and reduced levels of cytoplasmic APC were correlated to a low CDX2 expression in migrating colon cancer cells in vivo. These results suggest that a low CDX2 level has influence on the Wnt signaling in invasive colon cancer cells possibly promoting cellular migration.

BACKGROUND: A combination of antenatal and postnatal RhD prophylaxis is more effective in reducing D immunization in pregnancy than postnatal RhD prophylaxis alone. Based on the result from antenatal screening for the fetal RHD gene, antenatal RhD prophylaxis in Denmark is given only to those D- women who carry a D+ fetus. We present an evaluation of the first national clinical application of antenatal RHD screening. STUDY DESIGN AND METHODS: In each of the five Danish health care regions, blood samples were drawn from D- women in Gestational Week 25. DNA was extracted from the maternal plasma and analyzed for the presence of the RHD gene by real-time polymerase chain reaction targeting two RHD exons. Prediction of the fetal RhD type was compared with serologic typing of the newborn in 2312 pregnancies, which represented the first 6 months of routine analysis. RESULTS: For the detection of fetal RHD, the sensitivity was 99.9%. The accuracy was 96.5%. The recommendation for unnecessary antenatal RhD prophylaxis for women carrying a D- fetus was correctly avoided in 862 cases (37.3%), while 39 women (1.7%) were recommended for antenatal RhD prophylaxis unnecessarily. Two RHD+ fetuses (0.087%) were not detected, and antenatal RhIG was not given. CONCLUSION: These data represent the first demonstration of the reliability of routine antenatal fetal RHD screening in D-, pregnant women to ascertain the requirement for antenatal RhD prophylaxis. Our findings should encourage the implementation of such screening programs worldwide, to reduce the unnecessary use of RhIG.

BACKGROUND: A combination of antenatal and postnatal RhD prophylaxis is more effective in reducing D immunization in pregnancy than postnatal RhD prophylaxis alone. Based on the result from antenatal screening for the fetal RHD gene, antenatal RhD prophylaxis in Denmark is given only to those D- women who carry a D+ fetus. We present an evaluation of the first national clinical application of antenatal RHD screening. STUDY DESIGN AND METHODS: In each of the five Danish health care regions, blood samples were drawn from D- women in Gestational Week 25. DNA was extracted from the maternal plasma and analyzed for the presence of the RHD gene by real-time polymerase chain reaction targeting two RHD exons. Prediction of the fetal RhD type was compared with serologic typing of the newborn in 2312 pregnancies, which represented the first 6 months of routine analysis. RESULTS: For the detection of fetal RHD, the sensitivity was 99.9%. The accuracy was 96.5%. The recommendation for unnecessary antenatal RhD prophylaxis for women carrying a D- fetus was correctly avoided in 862 cases (37.3%), while 39 women (1.7%) were recommended for antenatal RhD prophylaxis unnecessarily. Two RHD+ fetuses (0.087%) were not detected, and antenatal RhIG was not given. CONCLUSION: These data represent the first demonstration of the reliability of routine antenatal fetal RHD screening in D-, pregnant women to ascertain the requirement for antenatal RhD prophylaxis. Our findings should encourage the implementation of such screening programs worldwide, to reduce the unnecessary use of RhIG.