The immune-modulating pregnancy-specific glycoproteins evolve rapidly and their presence correlates with hemochorial placentation in primates

BACKGROUND Pregnancy-specific glycoprotein (PSG) genes belong to the carcinoembryonic antigen (CEA) gene family, within the immunoglobulin gene superfamily. In humans, 10 PSG genes encode closely related secreted glycoproteins. They are exclusively expressed in fetal syncytiotrophoblast cells and represent the most abundant fetal proteins in the maternal blood. In recent years, a role in modulation of the maternal immune system possibly to avoid rejection of the semiallogeneic fetus and to facilitate access of trophoblast cells to maternal resources via the blood system has been suggested. Alternatively, they could serve as soluble pathogen decoy receptors like other members of the CEA family. Despite their clearly different domain organization, similar functional properties have also been observed for murine and bat PSG. As these species share a hemochorial type of placentation and a seemingly convergent formation of PSG genes during evolution, we hypothesized that hemochorial placentae support the evolution of PSG gene families. RESULTS To strengthen this hypothesis, we have analyzed PSG genes in 57 primate species which exhibit hemochorial or epitheliochorial placentation. In nearly all analyzed apes some 10 PSG genes each could be retrieved from genomic databases, while 6 to 24 PSG genes were found in Old World monkey genomes. Surprisingly, only 1 to 7 PSG genes could be identified in New World monkeys. Interestingly, no PSG genes were found in more distantly related primates with epitheliochorial placentae like lemurs and lorises. The exons encoding the putative receptor-binding domains exhibit strong selection for diversification in most primate PSG as revealed by rapid loss of orthologous relationship during evolution and high ratios of nonsynonymous and synonymous mutations. CONCLUSION The distribution of trophoblast-specific PSGs in primates and their pattern of selection supports the hypothesis that PSG are still evolving to optimize fetal-maternal or putative pathogen interactions in mammals with intimate contact of fetal cells with the immune system of the mother like in hemochorial placentation

Coevolution of paired receptors in Xenopus carcinoembryonic antigen-related cell adhesion molecule families suggests appropriation as pathogen receptors

BACKGROUND: In mammals, CEACAM1 and closely related members represent paired receptors with similar extracellular ligand-binding regions and cytoplasmic domains with opposing functions. Human CEACAM1 and CEACAM3 which have inhibitory ITIM/ITSM and activating ITAM-like motifs, respectively, in their cytoplasmic regions are such paired receptors. Various bacterial pathogens bind to CEACAM1 on epithelial and immune cells facilitating both entry into the host and down-regulation of the immune response whereas interaction with granulocyte-specific CEACAM3 leads to their uptake and destruction. It is unclear whether paired CEACAM receptors also exist in other vertebrate clades. RESULTS: We identified more than 80 ceacam genes in Xenopus tropicalis and X. laevis. They consist of two subgroups containing one or two putative paired receptor pairs each. Analysis of genomic sequences of paired receptors provide evidence that their highly similar ligand binding domains were adjusted by recent gene conversion events. In contrast, selection for diversification is observed among inhibitory receptor orthologs of the two frogs which split some 60 million years ago. The allotetraploid X. laevis arose later by hybridization of two closely related species. Interestingly, despite the conservation of the genomic landscape surrounding the homeologous ceacam loci only one locus resembles the one found in X. tropicalis. From the second X. laevis locus more than 80 % of the ceacam genes were lost including 5 of the 6 paired receptor genes. This suggests that once the gene for one of the paired receptors is lost the remaining gene cluster degrades rapidly probably due to lack of selection pressure exerted by pathogens. CONCLUSIONS: The presence of paired receptors and selection for diversification suggests that also in amphibians CEACAM1-related inhibitory proteins are or were used as pathogen receptors

PROPAGATION OF WAVE PACKETS FOR SYSTEMS PRESENTING CODIMENSION 1 CROSSINGS

We analyze the propagation of coherent states through general systems of pseudodifferential form associated with Hamiltonian presenting codimension one eigen-value crossings. In particular, we calculate precisely the non adiabatic effects of the crossing in terms of a transition operator

Asymptotic initial value representation of the solutions of semi-classical systems presenting smooth codimension one crossings

This paper is devoted to the construction of approximations of the propagator associated with a semi-classical matrix-valued Schr\"odinger operator with symbol presenting smooth eigenvalues crossings. Inspired by the approach of the theoretical chemists Herman and Kluk who propagated continuous superpositions of Gaussian wave-packets for scalar equations, we consider frozen and thawed Gaussian initial value representations that incorporate classical transport and branching processes along a hopping hypersurface. Based on the Gaussian wave-packet framework, our result relies on an accurate analysis of the solutions of the associated Schr\"odinger equation for data that are vector-valued wave-packets. We prove that these solutions are asymptotic to wavepackets at any order in terms of the semi-classical parameter

CEACAM1 recognition by bacterial pathogens is species-specific

<p>Abstract</p> <p>Background</p> <p>Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), an immunoglobulin (Ig)-related glycoprotein, serves as cellular receptor for a variety of Gram-negative bacterial pathogens associated with the human mucosa. In particular, <it>Neisseria gonorrhoeae</it>, <it>N. meningitidis</it>, <it>Moraxella catarrhalis</it>, and <it>Haemophilus influenzae </it>possess well-characterized CEACAM1-binding adhesins. CEACAM1 is typically involved in cell-cell attachment, epithelial differentiation, neovascularisation and regulation of T-cell proliferation, and is one of the few CEACAM family members with homologues in different mammalian lineages. However, it is unknown whether bacterial adhesins of human pathogens can recognize CEACAM1 orthologues from other mammals.</p> <p>Results</p> <p>Sequence comparisons of the amino-terminal Ig-variable-like domain of CEACAM1 reveal that the highest sequence divergence between human, murine, canine and bovine orthologues is found in the β-strands comprising the bacteria-binding CC'FG-face of the Ig-fold. Using GFP-tagged, soluble amino-terminal domains of CEACAM1, we demonstrate that bacterial pathogens selectively associate with human, but not other mammalian CEACAM1 orthologues. Whereas full-length human CEACAM1 can mediate internalization of <it>Neisseria gonorrhoeae </it>in transfected cells, murine CEACAM1 fails to support bacterial internalization, demonstrating that the sequence divergence of CEACAM1 orthologues has functional consequences with regard to bacterial recognition and cellular invasion.</p> <p>Conclusions</p> <p>Our results establish the selective interaction of several human-restricted bacterial pathogens with human CEACAM1 and suggest that co-evolution of microbial adhesins with their corresponding receptors on mammalian cells contributes to the limited host range of these highly adapted infectious agents.</p

Species-specific evolution of immune receptor tyrosine based activation motif-containing CEACAM1-related immune receptors in the dog

Background: Although the impact of pathogens on the evolution of the mammalian immune system is still under debate, proteins, which both regulate immune responses and serve as cellular receptors for pathogens should be at the forefront of pathogen-driven host evolution. The CEA ( carcinoembryonic antigen) gene family codes for such proteins and indeed shows tremendous species-specific variation between human and rodents. Since little is known about the CEA gene family in other lineages of placental mammals, we expected to gain new insights into the evolution of the rapidly diverging CEA family by analyzing the CEA family of the dog. Results: Here we describe the complete CEA gene family in the dog. We found that the gene coding for the ITIM-bearing immunoregulatory molecule CEACAM1 gave rise to a recent expansion of the canine CEA gene family by gene duplication, similar to that previously found in humans and mice. However, while the murine and human CEACAMs (carcinoembryonic antigen-related cell adhesion molecules) are predominantly secreted and GPI-anchored, respectively, in the dog, most of the CEACAMs represent ITAM-bearing transmembrane proteins. One of these proteins, CEACAM28, exhibits nearly complete sequence identity with the ligand-binding N domain of CEACAM1, but antagonizing signaling motifs in the cytoplasmic tail. Comparison of nonsynonymous and synonymous substitutions indicates that the CEACAM28 N domain is under the strongest purifying selection of all canine CEACAM1-related CEACAMs. In addition, CEACAM28 shows a similar expression pattern in resting immune cells and tissues as CEACAM1. However, upon activation CEACAM28 mRNA and CEACAM1 mRNA are differentially regulated. Conclusion: Thus, CEACAM1 and CEACAM28 are the first paired immune receptors identified within the CEA gene family, which are expressed on T cells and are most likely involved in the fine-tuning of T cell responses. The direction of gene conversion accompanied by purifying selection and expression in immune cells suggests the possibility that CEACAM28 evolved in response to selective pressure imposed by species-specific pathogens

Relationships between Playing Time and Selected NBA Combine Test Performance in Division I Mid-Major Basketball Players

International Journal of Exercise Science 13(4): 583-596, 2020. There has been limited analyses of DI mid-major male basketball players, and no analyses of relationships between athletic abilities and playing time in this population. The purpose of this study was to (1) describe and compare backcourt and frontcourt players from one mid-major team and (2) determine if there were relationships between playing time (total minutes, total games played, minutes per game) and select tests from the NBA Combine (height, body mass, standing reach, and wingspan; countermovement [VJ] and approach [AppVJ vertical jump], lane agility drill, ¾ court sprint, and 83.91-kg bench press). A retrospective analysis of data from the 2018 season for a men’s DI team (n = 10) was conducted. Performance testing was completed in the pre-season, and playing time metrics were collated by the team’s staff over the season. Players were split into backcourt (n = 6) and frontcourt (n = 4) groups and compared via independent samples t-tests (p \u3c 0.05) and effect sizes (d). Pearson’s correlations calculated relationships between playing time metrics and the NBA combine test data (p \u3c 0.05). When compared to the backcourt group, the frontcourt group were significantly taller, heavier, had a greater standing reach and wingspan, and performed poorer in the VJ, AppVJ, and ¾ court sprint (d = 1.49-3.45). There were no significant relationships between playing time and any NBA Combine test (r = -0.363-0.511). Basketball-specific skill may have a larger impact on playing time in this mid-major team. However, the mid-major players in this study may have had above-average athletic abilities as measured by NBA combine testing, limiting correlations with playing time

3D Simulationen zur Fischdurchgängigkeit am Flusskraftwerk Bannwil

Aufsatz veröffentlicht in: "Wasserbau-Symposium 2021: Wasserbau in Zeiten von Energiewende, Gewässerschutz und Klimawandel, Zurich, Switzerland, September 15-17, 2021, Band 1" veröffentlicht unter: https://doi.org/10.3929/ethz-b-00049975