CGM2, a Member of the Carcinoembryonic Antigen Gene Family is Down- Regulated in Colorectal Carcinomas

We have determined the precise chromosomal location, the exon structure, and the expression pattern of CGM2, a member of the carcinoembryonic antigen (CEA) gene family. CGM2 cDNA was amplified by reverse transcription-polymerase chain reaction (RT/PCR) from the colon adenocarcinoma cell line, LS174T. A defective exon is missing from this cDNA clone, leading to a novel domain organization for the human CEA family with two immunoglobulin-like domains. The derived C-terminal domain predicts that the CGM2 protein is membrane-bound through a glycosyl phosphatidylinositol anchor. RT/PCR analyses identified CGM2 transcripts in mucinous ovarian and colonic adenocarcinomas as well as in adjacent colonic tissue, but not in other tumors including leukocytes from six chronic myeloid leukemia patients. Thus, unlike several other family members, CGM2 is not expressed in granulocytes but reveals a more CEA-like expression pattern. Northern blot analyses identified a 2.5-kilobase CGM2 mRNA that is strongly down-regulated in colonic adenocarcinomas compared with adjacent colonic mucosa, suggesting a possible tumor suppressor function. In addition, a 3.2- kilobase transcript was observed in a number of colon tumors that is not detectable in normal colonic tissue. This mRNA species could represent a tumor-specific CGM2 splice variant

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

Homogeneous dielectric heating in large microwave ovens by excitation of multiple eigenmodes at their resonance frequencies

[EN] The proper use of microwave heating can significantly increase the production cycle time and energy efficiency in industrial heating processes compared to conventional heating methods. The main challenge of this technique is to improve the temperature uniformity in the product exposed to standing waves inside the microwave oven. In opposite to the magnetron, solid-state amplifiers (SSA) offer the possibility to increase the homogeneity by changing the amplitude, frequency and phase with the help of intelligent control methods [1]. In this work, the variation of the frequency and the amplitude of the SSA is considered. The multimode microwave oven used in the experiment has an industrial size of 535 mm x 510 mm x 395 mm (Figure 1). The SSA was operated in the frequency range from 2.4 GHz to 2.5 GHz. It consisted of a new 300 W solid state microwave source from HBH microwave GmbH, Germany. An antenna system was developed based on numerical simulation with CST Microwave Studio. The positions of four loop antennas were optimized to excite at least 90 % of the possible 32 eigenmodes [2] of the unloaded cavity. At the roof of the cavity, an IR camera was installed to observe the temperature distribution of the load during heating. A sheet of paper was used as the thermal load. It was placed on a PTFE plate as a sample holder. Figure 1 exemplary illustrates the comparison of the simulated power distribution with the measured temperature distribution for two representative eigenmodes. As can be expected from the figures, an optimized combination of different modes will lead to a significantly improved temperature uniformity in the material. Latest results obtained with different type of loads will be presented.The authors acknowledge the financial support by the Federal Ministry for Economic Affairs and Energy of Germany in the project ZF4204602PR6.Neumaier, D.; Sanseverino, S.; Link, G.; Jelonnek, J. (2019). Homogeneous dielectric heating in large microwave ovens by excitation of multiple eigenmodes at their resonance frequencies. En AMPERE 2019. 17th International Conference on Microwave and High Frequency Heating. Editorial Universitat Politècnica de València. 166-173. https://doi.org/10.4995/AMPERE2019.2019.9877OCS16617

Path-designed 3D printing for topological optimized continuous carbon fibre reinforced composite structures

In current 3D printing technologies, it remains a great challenge to print continuous carbon fibre reinforced composites with complex shapes and high mechanical performances. The main reason lies in the limitation of printing path design, which cannot guarantee to print carbon fibres along load transmission paths of composite parts. Here we address this issue by proposing an ingenious path-designed 3D (PD-3D) printing approach that considers the load transmission path and anisotropic property of the continuous carbon fibre reinforced filament. Complex structures of carbon fibre reinforced composites, with enhanced lightweight, were demonstrated. Such structures of carbon fibres paving along load transmission paths, greatly reduce stress concentration and achieve a quasi-isotropic performance. By comparing printed specimens with drilled holes and semicircles, the PD-3D printed specimens with holes and semicircles are 67.5% and 62.4% higher in tensile and flexural strength, respectively. And the strength to weight ratio of the tensile and flexural specimens also increase by 55.1% and 35.2%, compared with the drilled ones

Direct-Pathway Striatal Neurons Regulate the Retention of Decision-Making Strategies

The dorsal striatum has been implicated in reward-based decision making, but the role played by specific striatal circuits in these processes is essentially unknown. Using cell phenotype-specific viral vectors to express engineered G-protein-coupled DREADD (designer receptors exclusively activated by designer drugs) receptors, we enhanced G(i/o)- or G(s)-protein-mediated signaling selectively in direct-pathway (striatonigral) neurons of the dorsomedial striatum in Long–Evans rats during discrete periods of training of a high versus low reward-discrimination task. Surprisingly, these perturbations had no impact on reward preference, task performance, or improvement of performance during training. However, we found that transiently increasing G(i/o) signaling during training significantly impaired the retention of task strategies used to maximize reward obtainment during subsequent preference testing, whereas increasing G(s) signaling produced the opposite effect and significantly enhanced the encoding of a high-reward preference in this decision-making task. Thus, the fact that the endurance of this improved performance was significantly altered over time—long after these neurons were manipulated—indicates that it is under bidirectional control of canonical G-protein-mediated signaling in striatonigral neurons during training. These data demonstrate that cAMP-dependent signaling in direct-pathway neurons play a well-defined role in reward-related behavior; that is, they modulate the plasticity required for the retention of task-specific information that is used to improve performance on future renditions of the task

Carcinoembryonic Antigen Gene Family

The carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin supergene family and can be divided into two main subgroups based on sequence comparisons. In humans it is clustered on the long arm of chromosome 19 and consists of approximately 20 genes. The CEA subgroup genes code for CEA and its classical crossreacting antigens, which are mainly membrane-bound, whereas the other subgroup genes encode the pregnancy-specific glycoproteins (PSG), which are secreted. Splice variants of individual genes and differential post-translational modifications of the resulting proteins, e.g., by glycosylation, indicate a high complexity in the number of putative CEA-related molecules. So far, only a limited number of CEA-related antigens in humans have been unequivocally assigned to a specific gene. Rodent CEA-related genes reveal a high sequence divergence and, in part, a completely different domain organization than the human CEA gene family, making it difficult to determine individual gene counterparts. However, rodent CEA-related genes can be assigned to human subgroups based on similarity of expression patterns, which is characteristic for the subgroups. Various functions have been determined for members of the CEA subgroup in vitro, including cell adhesion, bacterial binding, an accessory role for collagen binding or ecto-ATPases activity. Based on all that is known so far on its biology, the clinical outlook for the CEA family has been reassessed

Transient neuronal inhibition reveals opposing roles of indirect and direct pathways in sensitization

The dorsal striatum plays an important role in the development of drug addiction; however, a precise understanding of the roles of striatopallidal (indirect) and striatonigral (direct) pathway neurons in regulating behaviors remains elusive. Using a novel approach that relies on the viral-mediated expression of an engineered GPCR (hM4D), we demonstrated that activation of hM4D receptors with clozapine-N-oxide (CNO) potently reduced striatal neuron excitability. When hM4D receptors were selectively expressed in either direct or indirect pathway neurons in rats, CNO did not change acute locomotor responses to amphetamine but altered behavioral plasticity associated with repeated drug treatment. Specifically, transiently disrupting striatopallidal neuronal activity facilitated behavioral sensitization whereas decreasing excitability of striatonigral neurons impaired its persistence. These findings suggest that acute drug effects can be parsed from the behavioral adaptations associated with repeated drug exposure and highlight the utility of this approach for deconstructing neuronal pathway contributions to behaviors such as sensitization