53 research outputs found

    Electrotropism of Maize (Zea mays L.) Roots (Facts and Artifacts)

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    Cloning, annotation and developmental expression of the chicken intestinal MUC2 gene

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    Intestinal mucin 2 (MUC2) encodes a heavily glycosylated, gel-forming mucin, which creates an important protective mucosal layer along the gastrointestinal tract in humans and other species. This first line of defense guards against attacks from microorganisms and is integral to the innate immune system. As a first step towards characterizing the innate immune response of MUC2 in different species, we report the cloning of a full-length, 11,359 bp chicken MUC2cDNA, and describe the genomic organization and functional annotation of this complex, 74.5 kb locus. MUC2 contains 64 exons and demonstrates distinct spatiotemporal expression profiles throughout development in the gastrointestinal tract; expression increases with gestational age and from anterior to posterior along the gut. The chicken protein has a similar domain organization as the human orthologue, with a signal peptide and several von Willebrand domains in the N-terminus and the characteristic cystine knot at the C-terminus. The PTS domain of the chicken MUC2 protein spans ~1600 amino acids and is interspersed with four CysD motifs. However, the PTS domain in the chicken diverges significantly from the human orthologue; although the chicken domain is shorter, the repetitive unit is 69 amino acids in length, which is three times longer than the human. The amino acid composition shows very little similarity to the human motif, which potentially contributes to differences in the innate immune response between species, as glycosylation across this rapidly evolving domain provides much of the musical barrier. Future studies of the function of MUC2 in the innate immune response system in chicken could provide an important model organism to increase our understanding of the biological significance of MUC2 in host defense and highlight the potential of the chicken for creating new immune-based therapies

    Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

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    Abstract: Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10−10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10−10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis

    Dynamic Secure Aspect Modeling with UML: From Models to Code

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    Abstract. Security engineering deals with modeling, analysis, and implementation of complex security mechanisms. The dynamic nature of such mechanisms makes it difficult to anticipate undesirable emergent behavior. In this work, we propose an approach to develop and analyze security-critical specifications and implementations using aspect-oriented modeling. Since we focus on the dynamic views of a system, our work is complementary to existing approaches to security aspects mostly concerned with static views. Our approach includes a link to implementations in so far as the code which is constructed from the models can be analyzed automatically for satisfaction of the security requirements stated in the UML diagrams. We present tool support for our approach.

    Instantiation-based automated reasoning: From theory to practice. In

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    Instantiation-based automated reasoning aims at combining the efficiency of propositional SAT and SMT technologies with the expressiveness of firstorder logic. Propositional SAT and SMT solvers are probably the most successful reasoners applied to real-world problems, due to extremely efficient propositional methods and optimized implementations. However, the expressiveness of firstorder logic is essential in many applications ranging from formal verification of software and hardware to knowledge representation and querying. Therefore, there is a growing demand to integrate efficient propositional and more generally ground reasoning modulo theories into first-order reasoning. The basic idea behind instantiation-based reasoning is to interleave smart generation of instances of first-order formulae with propositional type reasoning. Instantiation-based methods can be divided into two major categories: (i) finegrained interleaving of instantiation with efficient propositional inference rules, and (ii) modular combination of instantiation and propositional reasoning. Examples from the first category include the disconnection calculus (DCTP) [8
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