cDNA and Gene Analyses Imply a Novel Structure for a Rat Carcinoembryonic Antigen-related Protein

The gene encoding the human tumor marker carcinoembryonic antigen (CEA) belongs to a gene family which can be subdivided into the CEA and the pregnancy-specific glycoprotein subgroups. The corresponding proteins are members of the immunoglobulin superfamily, characterized through the presence of one IgV-like domain and a varying number of IgC-like domains. Since the function of the CEA family is not well understood, we decided to establish an animal model in the rat to study its tissue- specific and developmental stage-dependent expression. To this end, we have screened an 18-day rat placenta cDNA library with a recently isolated fragment of a rat CEA-related gene. Two overlapping clones containing the complete coding region for a putative 709 amino acid protein (rnCGM1; Mr = 78,310) have been characterized. In contrast to all members of the human CEA family, this rat CEA-related protein consists of five IgV-like domains and only one IgC-like domain. This novel structure, which has been confirmed at the genomic level might have important functional implications. Due to the rapid evolutionary divergence of the rat and human CEA gene families it is not possible to assign rnCGM1 to its human counterpart. However, the predominant expression of the rnCGM1 gene in the placenta suggests that it could be analogous to one of the human pregnancy-specific glycoprotein genes

Spatiotemporal Expression of Pregnancy-Specific Glycoprotein Gene rnCGMl in Rat Placenta

As a basis towards a better understanding of the role of the pregnancy-specific glycoprotein (PSG) family in the maintenance of pregnancy, detailed investigations are described on the expression of a recently identified rat PSG gene (rnCGM1) at the mRNA and protein levels. Using specific oligonucleotide primers, rnCGM1 transcripts were identified after reverse transcription, polymerase chain reaction, and hybridization with a radiolabelled, internal oligonucleotide. Transcripts were only found in significant amounts in placenta. In situ hybridization visualized rnCGM1 transcripts at day 14 post coitum (p.c.), in secondary trophoblast giant cells and in the spongiotrophoblast. Only those secondary giant cells lining the maternal decidua were positive. In contrast, primary giant cells did not contain rnCGM1 mRNA. At day 18 p.c., rnCGM1. transcripts were almost exclusively detectable in the spongiotrophoblast. No rnCGM1 transcripts were found in rat embryos of these two developmental stages. Rabbit antisera were generated against the amino-terminal immunoglobulin variable-like domain and against a synthetic peptide containing the last 13 carboxy-terminal amino acids of rnCGM1. Bothe antisera recognized a 124 kDa protein in day 18 rat placental extracts as identified by Western blot analysis. The anti-peptide antiserum recognized a 116 kDa protein in the serum of a 14 day p.c. pregnant rat that is absent from the sera of non-pregnant females. Taken together, these results confirm exclusive expression of rnCGM1 in the rat trophoblast, but unlike human PSG, negligible or no expression is found in other organs, such as fetal liver or salivary glands, indicating a more specialized function of rnCGM1. Its spatiotemporal expression pattern is conducive with a potential role of PSG in protecting the fetus against the maternal immune system and/or in regulating the invasive growth of trophoblast cells

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

Absence of an embryonic stem cell DNA methylation signature in human cancer.

BackgroundDifferentiated cells that arise from stem cells in early development contain DNA methylation features that provide a memory trace of their fetal cell origin (FCO). The FCO signature was developed to estimate the proportion of cells in a mixture of cell types that are of fetal origin and are reminiscent of embryonic stem cell lineage. Here we implemented the FCO signature estimation method to compare the fraction of cells with the FCO signature in tumor tissues and their corresponding nontumor normal tissues.MethodsWe applied our FCO algorithm to discovery data sets obtained from The Cancer Genome Atlas (TCGA) and replication data sets obtained from the Gene Expression Omnibus (GEO) data repository. Wilcoxon rank sum tests, linear regression models with adjustments for potential confounders and non-parametric randomization-based tests were used to test the association of FCO proportion between tumor tissues and nontumor normal tissues. P-values of < 0.05 were considered statistically significant.ResultsAcross 20 different tumor types we observed a consistently lower FCO signature in tumor tissues compared with nontumor normal tissues, with 18 observed to have significantly lower FCO fractions in tumor tissue (total n = 6,795 tumor, n = 922 nontumor, P < 0.05). We replicated our findings in 15 tumor types using data from independent subjects in 15 publicly available data sets (total n = 740 tumor, n = 424 nontumor, P < 0.05).ConclusionsThe results suggest that cancer development itself is substantially devoid of recapitulation of normal embryologic processes. Our results emphasize the distinction between DNA methylation in normal tightly regulated stem cell driven differentiation and cancer stem cell reprogramming that involves altered methylation in the service of great cell heterogeneity and plasticity

Enhancing the charging power of quantum batteries

Can collective quantum effects make a difference in a meaningful thermodynamic operation? Focusing on energy storage and batteries, we demonstrate that quantum mechanics can lead to an enhancement in the amount of work deposited per unit time, i.e., the charging power, when $N$ batteries are charged collectively. We first derive analytic upper bounds for the collective \emph{quantum advantage} in charging power for two choices of constraints on the charging Hamiltonian. We then highlight the importance of entanglement by proving that the quantum advantage vanishes when the collective state of the batteries is restricted to be in the separable ball. Finally, we provide an upper bound to the achievable quantum advantage when the interaction order is restricted, i.e., at most $k$ batteries are interacting. Our result is a fundamental limit on the advantage offered by quantum technologies over their classical counterparts as far as energy deposition is concerned.Comment: In this new updated version Theorem 1 has been changed with Proposition 1. The paper has been published on PRL, and DOI included accordingl

Vertex-element models for anisotropic growth of elongated plant organs

New tools are required to address the challenge of relating plant hormone levels, hormone responses, wall biochemistry and wall mechanical properties to organ-scale growth. Current vertex-based models (applied in other contexts) can be unsuitable for simulating the growth of elongated organs such as roots because of the large aspect ratio of the cells, and these models fail to capture the mechanical properties of cell walls in sufficient detail. We describe a vertex-element model which resolves individual cells and includes anisotropic non-linear viscoelastic mechanical properties of cell walls and cell division whilst still being computationally efficient. We show that detailed consideration of the cell walls in the plane of a 2D simulation is necessary when cells have large aspect ratio, such as those in the root elongation zone of Arabidopsis thaliana, in order to avoid anomalous transverse swelling. We explore how differences in the mechanical properties of cells across an organ can result in bending and how cellulose microfibril orientation affects macroscale growth. We also demonstrate that the model can be used to simulate growth on realistic geometries, for example that of the primary root apex, using moderate computational resources. The model shows how macroscopic root shape can be sensitive to fine-scale cellular geometries

Interfaces for Cloning in Immersive Virtual Environments

Three-dimensional objects in many application domains, such as architecture and construction, can be extremely complex and can consist of a large number of components. However, many of these complex objects also contain a great deal of repetition. Therefore, cloning techniques, which generate multiple spatially distributed copies of an object to form a repeated pattern, can be used to model these objects more efficiently. Such techniques are important and useful in desktop three-dimensional modeling systems, but we are not aware of any cloning techniques designed for immersive virtual environments (VEs). In this paper, we present an initial effort toward the design and development of such interfaces. We define the design space of the cloning task, and present five novel VE interfaces for cloning, then articulate the design rationale. We have also performed a usability study intended to elicit subjective responses with regard to affordance, feedback, attention, perceived usefulness, ease of use, and ease of learning in these interfaces. The study resulted in four major conclusions. First, slider widgets are better suited for discrete than for continuous numeric input. Second, the attentional requirements of the interface increase with increased degrees-of-freedom associated with widgets. Third, users prefer constrained widget movement, although more degrees-of-freedom allow more efficient parameter setting. Finally, appropriate feedback can reduce the cognitive load. The lessons we learned will influence our continuing design of cloning techniques, and these techniques will ultimately be applied to VE applications for design, construction, and prototyping