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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

A consensus document on definition and diagnostic criteria for orthorexia nervosa

Purpose: Since the term orthorexia nervosa (ON) was coined from the Greek (ὀρθός, right and ὄρεξις, appetite) in 1997 to describe an obsession with “correct” eating, it has been used worldwide without a consistent definition. Although multiple authors have proposed diagnostic criteria, and many theoretical papers have been published, no consensus definition of ON exists, empirical primary evidence is limited, and ON is not a standardized diagnosis. These gaps prevent research to identify risk and protective factors, pathophysiology, functional consequences, and evidence-based therapeutic treatments. The aims of the current study are to categorize the common observations and presentations of ON pathology among experts in the eating disorder field, propose tentative diagnostic criteria, and consider which DSM chapter and category would be most appropriate for ON should it be included. Methods: 47 eating disorder researchers and multidisciplinary treatment specialists from 14 different countries across four continents completed a three-phase modified Delphi process, with 75% agreement determined as the threshold for a statement to be included in the final consensus document. In phase I, participants were asked via online survey to agree or disagree with 67 statements about ON in four categories: A–Definition, Clinical Aspects, Duration; B–Consequences; C–Onset; D–Exclusion Criteria, and comment on their rationale. Responses were used to modify the statements which were then provided to the same participants for phase II, a second round of feedback, again in online survey form. Responses to phase II were used to modify and improve the statements for phase III, in which statements that met the predetermined 75% of agreement threshold were provided for review and commentary by all participants. Results: 27 statements met or exceeded the consensus threshold and were compiled into proposed diagnostic criteria for ON. Conclusions: This is the first time a standardized definition of ON has been developed from a worldwide, multidisciplinary cohort of experts. It represents a summary of observations, clinical expertise, and research findings from a wide base of knowledge. It may be used as a base for diagnosis, treatment protocols, and further research to answer the open questions that remain, particularly the functional consequences of ON and how it might be prevented or identified and intervened upon in its early stages. Although the participants encompass many countries and disciplines, further research will be needed to determine if these diagnostic criteria are applicable to the experience of ON in geographic areas not represented in the current expert panel. Level of evidence_ Level V: opinions of expert committee

Strain specific maturation of Dendritic cells and production of IL-1β controls CD40-driven colitis

Intestinal integrity is maintained by balanced numbers of CD103 + Dendritic cells (DCs), which generate peripherally induced regulatory T cells (iTregs). We have developed a mouse model where DC-specific constitutive CD40 signals caused a strong reduction of CD103 + DCs in the lamina propria (LP) and intestinal lymph nodes (LN). As a consequence, also iTregs were strongly reduced and transgenic mice on the C57Bl/6-background (B6) developed fatal colitis. Here we describe that transgenic mice on a pure Balb/c-background (B/c) do not show any pathologies, while transgenic C57Bl/6 x Balb/c (F1) mice develop weak colon inflammation, without fatal colitis. This graded pathology correlated with the effects of CD40-signalling on DCs in each background, with striking loss of CD103 + DCs in B6, but reduced in F1 and diminished in B/c background. We further show direct correlation of CD103 + DC-numbers with numbers of iTregs, the frequencies of which behave correspondingly. Striking effects on B6-DCs reflected robust loss of surface MHCII, known to be crucial for iTreg induction. Furthermore, elevated levels of IL-23 together with IL-1, found only in B6 mice, support generation of intestinal IFN-γ + IL-17 + Th17 cells and IFN-γ + Th1 cells, responsible for onset of disease. Together, this demonstrates a novel aspect of colitis-control, depending on genetic background. Moreover, strain-specific environmental sensing might alter the CD103 + DC/iTreg-axis to tip intestinal homeostatic balance to pathology

Novel spontaneous deletion of artemis exons 10 and 11 in mice leads to T- and B-cell deficiency.

Here we describe a novel, spontaneous, 4035 basepairs long deletion in the DNA cross-link repair 1C (Dclre1c)-locus in C57BL/6-mice, which leads to loss of exons 10 and 11 of the gene encoding for Artemis, a protein involved into V(D) J-recombination of antigen receptors of T and B cells. While several spontaneous mutations of Artemis have been described to cause SCID in humans, in mice, only targeted deletions by knockout technology are known to cause the same phenotype so far. The deletion we observed causes a loss of Artemis function in the C57BL/6 strain and, consequently, the absence of T and B cells, in presence of normal numbers of NK cells and cells of the myeloid lineage. Thus, for the first time we present T(-)B(-)NK(+) severe combined immunodeficiency (SCID) phenotype after spontaneously occurring modification of Artemis gene in mice. Our mouse model may serve as a valuable tool to study mechanisms as well as potential therapies of SCID in humans

Initial characterization of cell subsets in the spleens of mutant mice.

<p>(A) Single cell suspensions of spleens were stained for B cells (CD19⁺B220⁺) or T cells (CD4⁺ or CD8⁺), which were further analyzed for expression of CD3 (lower panel). Cells were gated on live lymphocytes. (B) Single cell suspensions of spleens were stained with the indicated antibodies to identify DC (CD11c⁺MHCII⁺), NK cells (NK1.1 ⁺ CD3^-), granulocytes (Gr1 ⁺ CD3^-) and CD11b⁺ monocytes. FACS-plots and statistics are representative results from one out of six experiments with similar outcome (n=3 mice per group). Bar graphs represent mean number of live cells ± SD in the respective gate.</p

Single nucleotide polymorphism (SNP) analysis of mutant mice.

<p>(A) Mutant mice on C57BL/6 background were crossed to C3H and the offspring (F1) was used for an intercross yielding F2 animals. Blood of these animals was analyzed for the percentage of T cells (TCR-β ⁺ DX5^-) and B cells (CD19⁺MHCII⁺). F2 animals were grouped according to the presence (unaffected) or absence (affected) of T and B cells and affected animals were used for SNP-analyses. (B) Graphical representation of SNP distribution in randomly selected F2 and control animals. SNPs derived from C57BL/6 are in blue, SNPs from C3H are in red and heterogenous SNPs are yellow. Shown are only informative SNPs at the beginning of chromosome 2. The chip contained 377 SNP of which 244 were informative in our cross. In total we performed SNP-analyses from 57 F2 animals as well as from 6 F1, C57BL/6 and C3H control animals each.</p

Sequencing of <i>Dclre1c-</i>gene.

<p>(A) Two heterogeneous and four homogeneous mutant mice were analyzed using next-generation-sequencing techniques. Displayed is the coverage of the bases in exons 9 to 12. (B) Graphical representation of the genomic organization of <i>Dclr1c</i> between exons 9 and 12. Exons are indicated by black boxes, while arrows indicate primer binding-sites. The upper row represents the organization in the wild-type genome while the lower row represents the gene in the mutant. (C) Results of PCR reactions with the indicated primer sets. DNA was visualized on ethidium bromide agarose gels. (D) Primer p3f and p8r were used to amplify DNA from mutant animals and the purified PCR products were used for Sanger DNA-sequencing. The resulting sequences were aligned to the <i>Dclre1c</i>-sequence according to the “Gene” database of NCBI. (*) indicates matching bases, (-) indicates gaps in the alignment. Shown is the 5´ beginning of the deletion (before //) as well as the 3´ end of the deletion (after //).</p

Definition and diagnostic criteria for orthorexia nervosa: a narrative review of the literature

In some cases, detrimental consequences on health are generated by self-imposed dietary rules intended to promote health. The pursuit of an "extreme dietary purity" due to an exaggerated focus on food may lead to a disordered eating behavior called "orthorexia nervosa" (ON). ON raises a growing interest, but at present there is no universally shared definition of ON, the diagnostic criteria are under debate, and the psychometric instruments used in the literature revealed some flaws. This narrative review of the literature aims at assessing state of the art in ON definition, diagnostic criteria and related psychometric instruments and provides research propositions and framework for future analysis