BackgroundExpansions of gene families are predictive for ongoing genetic adaptation to environmental cues. We describe such an expansion of the carcinoembryonic antigen (CEA) gene family in certain bat families. Members of the CEA family in humans and mice are exploited as cellular receptors by a number of pathogens, possibly due to their function in immunity and reproduction. The CEA family is composed of CEA-related cell adhesion molecules (CEACAMs) and secreted pregnancy-specific glycoproteins (PSGs). PSGs are almost exclusively expressed by trophoblast cells at the maternal-fetal interface. The reason why PSGs exist only in a minority of mammals is still unknown.ResultsAnalysis of the CEA gene family in bats revealed that in certain bat families, belonging to the subgroup Yangochiroptera but not the Yinpterochiroptera subgroup an expansion of the CEA gene family took place, resulting in approximately one hundred CEA family genes in some species of the Vespertilionidae. The majority of these genes encode secreted PSG-like proteins (further referred to as PSG). Remarkably, we found strong evidence that the ligand-binding domain (IgV-like domain) of PSG is under diversifying positive selection indicating that bat PSGs may interact with structurally highly variable ligands. Such ligands might represent bacterial or viral pathogen adhesins. We have identified two distinct clusters of PSGs in three Myotis species. The two PSG cluster differ in the amino acids under positive selection. One cluster was only expanded in members of the Vespertilionidae while the other was found to be expanded in addition in members of the Miniopteridae and Mormoopidae. Thus one round of PSG expansion may have occurred in an ancestry of all three families and a second only in Vespertilionidae. Although maternal ligands of PSGs may exist selective challenges by two distinct pathogens seem to be likely responsible for the expansion of PSGs in Vespertilionidae.ConclusionsThe rapid expansion of PSGs in certain bat species together with selection for diversification suggest that bat PSGs could be part of a pathogen defense system by serving as decoy receptors and/or regulators of feto-maternal interactions.Electronic supplementary materialThe online version of this article (10.1186/s12864-017-4106-7) contains supplementary material, which is available to authorized users.
The reaction of substituted anilines and benzenesulfonyl chlorides has been used to prepare 49 substituted N-phenylbenzenesulfonamides of general formula 4-X-C 6 H 4 SO 2 NHC 6 H 4 -Y-4′. Their purity was checked by elemental analysis. The substituents X and Y include H, CH 3 , CH 3 O, Cl, Br, CN, and NO 2 . The dissociation constants of all compounds were determined by potentiometric titration in methanol, acetonitrile, N,N-dimethylformamide, and pyridine. The obtained dissociation constants, pK HA , were correlated with various sets of substituent constants. It was found that the effects of substituents X and Y on the dissociation are best described by using the Hammett equation with σ p constants and the Yukawa-Tsuno equation with σ p -and σ p constants, respectively. This result confirms the direct conjugation of Y substituent with the reaction centre. The explained variability using the additive model was above 96% in all the solvents used. The data also provided information about the transmission effect of the SO 2 group. The average dissociation constants were further processed by the latent variables methods, principal components and conjugated deviations analyses.
BackgroundThe CEA gene family is one of the most rapidly evolving gene families in the human genome. The founder gene of the family is thought to be an ancestor of the inhibitory immune checkpoint molecule CEACAM1. Comprehensive analyses of mammalian genomes showed that the CEA gene family is subject to tremendous gene family expansion and contraction events in different mammalian species. While in some species (e.g. rabbits) less than three CEACAM1 related genes exist, were in others (certain microbat species) up to 100 CEACAM1 paralogs identified. We have recently reported that the horse has also an extended CEA gene family. Since mechanisms of gene family expansion and diversification are not well understood we aimed to analyze the equine CEA gene family in detail.ResultsWe found that the equine CEA gene family contains 17 functional CEACAM1-related genes. Nine of them were secreted molecules and eight CEACAMs contain transmembrane and cytoplasmic domain exons, the latter being in the focus of the present report. Only one (CEACAM41) gene has exons coding for activating signaling motifs all other CEACAM1 paralogs contain cytoplasmic exons similar to that of the inhibitory receptor CEACAM1. However, cloning of cDNAs showed that only one CEACAM1 paralog contain functional immunoreceptor tyrosine-based inhibitory motifs in its cytoplasmic tail. Three receptors have acquired a stop codon in the transmembrane domain and two have lost their inhibitory motifs due to alternative splicing events. In addition, alternative splicing eliminated the transmembrane exon sequence of the putative activating receptor, rendering it to a secreted molecule. Transfection of eukaryotic cells with FLAG-tagged alternatively spliced CEACAMs indicates that they can be expressed in vivo. Thus detection of CEACAM41 mRNA in activated PBMC suggests that CEACAM41 is secreted by lymphoid cells upon activation.ConclusionsThe results of our study demonstrate that alternative splicing after gene duplication is a potent mechanism to accelerate functional diversification of the equine CEA gene family members. This potent mechanism has created novel CEACAM receptors with unique signaling capacities and secreted CEACAMs which potentially enables equine lymphoid cells to control distantly located immune cells.
Simulation-based training has seen an increased use of extended reality, that is, augmented reality (AR), virtual reality (VR) and mixed reality (MR) displays. The health professions have been using VR for simulation-based training more extensively than others. This method can offer the possibility of immediate feedback, which promotes more accurate training to self-correct mistakes in environments that are otherwise risky or provide unsafe conditions. The nuclear industry has attempted to seize the same digital and educational transformation to train their personnel to handle dangerous scenarios. We ran a pilot study with the aim of evaluating the VR training scenario developed for the specific target group and the acceptance of the VR technology itself for this kind of training. We used the Kirkpatrick framework to evaluate the training and the VR-HAM acceptance model to evaluate the acceptance of VR. A VR scenario was developed to test specific technical skills of nuclear power plant personnel. The 13 participants showed results within the basic level of the Kirkpatrick framework and held both positive reactions and concerns, that is, they enjoyed the training with VR and expressed concerns regarding the stability of the VR technology. The participants also showed positive attitudes towards the perceived ease of use and usefulness of the VR-HAM and its various constructs. Even though the COVID-19 pandemic limited our testing, we could show valuable data and positive attitudes and perceived ease by the participants. Simulation-based VR training could be an important complement to traditional training methods, especially where safety is a priority, but we still need to provide solid evidence.
Concerted evolution is often observed in multigene families such as the CEA gene family. As a result, sequence similarity of paralogous genes is significantly higher than expected from their evolutionary distance. Gene conversion, a "copy paste" DNA repair mechanism that transfers sequences from one gene to another and homologous recombination are drivers of concerted evolution. Nevertheless, some gene family members escape concerted evolution and acquire sufficient sequence differences that orthologous genes can be assigned in descendant species. Reasons why some gene family members can escape while others are captured by concerted evolution are poorly understood. By analyzing the entire ceA gene family in cattle (Bos taurus) we identified a member (CEACAM32) that was created by gene duplication and cooption of a unique transmembrane domain exon in the most recent ancestor of ruminants. CEACAM32 shows a unique, testis-specific expression pattern. Phylogenetic analysis indicated that CEACAM32 is not involved in concerted evolution of CEACAM1 paralogs in ruminants. However, analysis of gene conversion events revealed that CEACAM32 is subject to gene conversion but remarkably, these events are found in the leader exon and intron sequences but not in exons coding for the Ig-like domains. These findings suggest that natural selection hinders gene conversion affecting protein sequences of the mature protein and thereby support escape of CEACAM32 from concerted evolution.
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