Identification of a Carcinoembryonic Antigen Gene Family in the Rat

The existence of a carcinoembryonic antigen (CEA)-like gene family in rat has been demonstrated through isolation and sequencing of the N- terminal domain exons of presumably five discrete genes (rnCGM1-5). This finding will allow for the first time the study of functional and clinical aspects of the tumor marker CEA and related antigens in an animal model. Sequence comparison with the corresponding regions of members of the human CEA gene family revealed a relatively low similarity at the amino acid level, which indicates rapid divergence of the CEA gene family during evolution and explains the lack of cross- reactivity of rat CEA-like antigens with antibodies directed against human CEA. The N-terminal domains of the rat CEA-like proteins show structural similarity to immunoglobulin variable domains, including the presence of hypervariable regions, which points to a possible receptor function of the CEA family members. Although so far only one of the five rat CEA-like genes could be shown to be transcriptionally active, multiple mRNA species derived from other members of the rat CEA-like gene family have been found to be differentially expressed in rat placenta and liver

Cloning of a Carcinoembryonic Antigen Gene Family Member Expressed in Leukocytes of Chronic Myeloid Leukemia Patients and Bone Marrow

The carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin superfamily and can be subdivided into the CEA and pregnancy-specific glycoprotein subgroups. The basic structure of the encoded proteins consists of, in addition to a leader, one IgV-like and 2, 3, or 6 IgC-like domains. These domains are followed by varying COOH-terminal regions responsible for secretion, transmembrane anchoring, or insertion into the membrane by a glycosyl phosphatidylinositol tail. Here we report on the characterization of CGM6, a new member of the CEA gene subgroup, by complementary DNA cloning. The deduced coding region comprises 349 amino acids and consists of a leader, one IgV-like, two IgC-like domains, and a hydrophobic region, which is replaced by a glycosyl phosphatidylinositol moiety in the mature protein. CGM6 transcripts were only found thus far in leukocytes of chronic myeloid leukemia patients, in normal bone marrow, and in marginal amounts in normal granulocytes. The CGM6 gene product might, therefore, represent a myeloid marker. Analyses of CGM6 protein-expressing HeLa transfectants with monoclonal antibodies strongly indicate that the CGM6 gene codes for the CEA family member NCA-95

Mice Transgenic for the Human Carcinoembryonic Antigen Gene Maintain Its Spatiotemporal Expression Pattern

The tumor marker carcinoembryonic antigen (CEA) is predominantly expressed in epithelial cells along the gastrointestinal tract and in a variety of adenocarcinomas. As a basis for investigating its in vivo regulation and for establishing an animal model for tumor immunotherapy, transgenic mice were generated with a 33-kilobase cosmid clone insert containing the complete human CEA gene and flanking sequences. CEA was found in the tongue, esophagus, stomach, small intestine, cecum, colon, and trachea and at low levels in the lung, testis, and uterus of adult mice of independent transgenic strains. CEA was first detected at day 10.5 of embryonic development (embryonic day 10.5) in primary trophoblast giant cells and was found in the developing gut, urethra, trachea, lung, and nucleus pulposus of the vertebral column from embryonic day 14.5 onwards. From embryonic day 16.5 CEA was also visible in the nasal mucosa and tongue. Because this spatiotemporal expression pattern correlates well with that known for humans, it follows that the transferred genomic region contains all of the regulatory elements required for the correct expression of CEA. Furthermore, although mice apparently lack an endogenous CEA gene, the entire repertoire of transcription factors necessary for correct expression of the CEA transgene is conserved between mice and humans. After tumor induction, these immunocompetent mice will serve as a model for optimizing various forms of immunotherapy, using CEA as a target antigen

Cloning of the Complete Gene for Carcinoembryonic Antigen

Carcinoembryonic antigen (CEA) is a widely used tumor marker, especially in the surveillance of colonic cancer patients. Although CEA is also present in some normal tissues, it is apparently expressed at higher levels in tumorous tissues than in corresponding normal tissues. As a first step toward analyzing the regulation of expression of CEA at the transcriptional level, we have isolated and characterized a cosmid clone (cosCEA1), which contains the entire coding region of the CEA gene. A close correlation exists between the exon and deduced immunoglobulin-like domain borders. We have determined a cluster of transcriptional starts for CEA and the closely related nonspecific cross-reacting antigen (NCA) gene and have sequenced their putative promoters. Regions of sequence homology are found as far as approximately 500 nucleotides upstream from the translational starts of these genes, but farther upstream they diverge completely. In both cases we were unable to find classic TATA or CAAT boxes at their expected positions. To characterize the CEA and NCA promoters, we carried out transient transfection assays with promoter-indicator gene constructs in the CEA-producing adenocarcinoma cell line SW403, as well as in nonproducing HeLa cells. A CEA gene promoter construct, containing approximately 400 nucleotides upstream from the translational start, showed nine times higher activity in the SW403 than in the HeLa cell line. This indicates that cis-acting sequences which convey cell type-specific expression of the CEA gene are contained within this region

Chromosomal Localization of the Carcinoembryonic Antigen Gene Family and Differential Expression in Various Tumors

Carcinoembryonic antigen (CEA) is a glycoprotein which is important as a tumor marker for a number of human cancers. It is a member of a gene family comprising about 10 closely related genes. In order to characterize mUNAs transcribed from individual genes we have identified by DNA and RNA hybridization experiments, gene-specific sequences from the 3 ' noncoding regions of CEA, and of nonspecific cross-reacting antigen (NCA) mRNAs, which have been recently cloned. With these probes, CEA mRNAs with lengths of 3.5 and 3.0 kilobases and an NCA mRNA species of 2.5 kilobases were identified in various human tumors. A 2.2-kilobase mRNA species, however, could only be detected in leu kocytes of patients with chronic myeloid leukemia by hybridization with a probe from the immunoglobulin-like repeat domain of CEA. This region is known to be very similar among the various members of the CEA gene family, and indeed the probe hybridizes with all four mRNA species. In situ hybridization with a cross-hybridizing probe from the NCA gene localized the members of the CEA gene family to the short and to the long arm of chromosome 19. In addition, a CEA cDNA probe was found to hybridize to the long arm of chromosome 19 only

Experimental Evidence for the Incorporation of Two Metals at Equivalent Lattice Positions in Mixed-Metal Metal–Organic Frameworks

Metal–organic frameworks containing multiple metals distributed over crystallographically equivalent framework positions (mixed‐metal MOFs) represent an interesting class of materials, since the close vicinity of isolated metal centers often gives rise to synergistic effects. However, appropriate characterization techniques for detailed investigations of these mixed‐metal metal–organic framework materials, particularly addressing the distribution of metals within the lattice, are rarely available. The synthesis of mixed‐metal FeCuBTC materials in direct syntheses proved to be difficult and only a thorough characterization using various techniques, like powder X‐ray diffraction, X‐ray absorption spectroscopy and electron paramagnetic resonance spectroscopy, unambiguously evidenced the formation of a mixed‐metal FeCuBTC material with HKUST‐1 structure, which contained bimetallic Fe−Cu paddlewheels as well as monometallic Cu−Cu and Fe−Fe units under optimized synthesis conditions. The in‐depth characterization showed that other synthetic procedures led to impurities, which contained the majority of the applied iron and were impossible or difficult to identify using solely standard characterization techniques. Therefore, this study shows the necessity to characterize mixed‐metal MOFs extensively to unambiguously prove the incorporation of both metals at the desired positions. The controlled positioning of metal centers in mixed‐metal metal–organic framework materials and the thorough characterization thereof is particularly important to derive structure–property or structure–activity correlations

Regionalisation of asset values for risk analyses

International audienceIn risk analysis there is a spatial mismatch of hazard data that are commonly modelled on an explicit raster level and exposure data that are often only available for aggregated units, e.g. communities. Dasymetric mapping techniques that use ancillary information to disaggregate data within a spatial unit help to bridge this gap. This paper presents dasymetric maps showing the population density and a unit value of residential assets for whole Germany. A dasymetric mapping approach, which uses land cover data (CORINE Land Cover) as ancillary variable, was adapted and applied to regionalize aggregated census data that are provided for all communities in Germany. The results were validated by two approaches. First, it was ascertained whether population data disaggregated at the community level can be used to estimate population in postcodes. Secondly, disaggregated population and asset data were used for a loss evaluation of two flood events that occurred in 1999 and 2002, respectively. It must be concluded that the algorithm tends to underestimate the population in urban areas and to overestimate population in other land cover classes. Nevertheless, flood loss evaluations demonstrate that the approach is capable of providing realistic estimates of the number of exposed people and assets. Thus, the maps are sufficient for applications in large-scale risk assessments such as the estimation of population and assets exposed to natural and man-made hazards

Rapid incidence estimation from SARS-CoV-2 genomes reveals decreased case detection in Europe during summer 2020

By October 2021, 230 million SARS-CoV-2 diagnoses have been reported. Yet, a considerable proportion of cases remains undetected. Here, we propose GInPipe, a method that rapidly reconstructs SARS-CoV-2 incidence profiles solely from publicly available, time-stamped viral genomes. We validate GInPipe against simulated outbreaks and elaborate phylodynamic analyses. Using available sequence data, we reconstruct incidence histories for Denmark, Scotland, Switzerland, and Victoria (Australia) and demonstrate, how to use the method to investigate the effects of changing testing policies on case ascertainment. Specifically, we find that under-reporting was highest during summer 2020 in Europe, coinciding with more liberal testing policies at times of low testing capacities. Due to the increased use of real-time sequencing, it is envisaged that GInPipe can complement established surveillance tools to monitor the SARS-CoV-2 pandemic. In post-pandemic times, when diagnostic efforts are decreasing, GInPipe may facilitate the detection of hidden infection dynamics.Results - Method validation: in silico experiment. - Method validation: phylodynamics. - Reconstructed incidence histories. - Relative case detection rate. Discussion Method

Estimation of the regional stock of residential buildings as a basis for a comparative risk assessment in Germany

International audienceOne important prerequisite for a comparable quantitative risk assessment for different types of hazards (e.g., earthquakes, windstorms and floods) is the use of a common database about and financial appraisal of the assets at risk. For damage assessments it is necessary to represent the values at risk on a regional disaggregated scale and to intersect them with hazard scenarios. This paper presents a methodology and results of a financial appraisal of residential buildings for all communities in Germany. The calculated values are defined as replacement values for the reference year 2000. The resulting average replacement costs for residential buildings per inhabitant amount to EUR 46 600, with considerable differences between communities. The inventory can be used for the calculations of direct losses from various natural disasters within the project "Risk Map Germany''