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According to a widespread tradition, Laius was buried in Phocis after his death. Areview of the relevant passages in Statius’ Thebaid shows that the poeta doctus alludes to thisversion of the story, but he himself follows a different mythical variant: The body of Laiusremained unburied, which meant that his ghost could not cross the border river to theunderworld. In this way the denied or perverted burial, a dominant thematic concern in theThebaid, is projected back into the prehistory of the plot.

The effect of standard bakery concentrations of microbial transglutaminase (MTG) in wheat bread preparation on the immunoreactivity of sera of celiac disease (CD) patients was investigated. Immunoblotting using monoclonal antibodies specific to unmodified and/or deamidated gliadin showed no differences between control bread and MTG bread. Deamidation of gliadin could not be detected at standard MTG concentrations. Sera of CD patients were characterized using anti-gliadin and anti-deamidated gliadin peptide (DGP) enzyme-linked immunosorbent assay and grouped into DGP high- and low-titer pools. The recognition pattern obtained after using both CD sera pools for immunoblotting did not reveal differences between control and MTG-treated bread protein extracts. Our results indicate that MTG treatment of wheat bread prepared with typical MTG concentrations used in standard bakery processes does not lead to immunodetectable amounts of CD immunotoxic deamidated gliadins.

Background Factor XIII (FXIII) is the final enzyme of the coagulation cascade. While the other enzymatic coagulation factors are proteases, FXIII belongs to the transglutaminase family. FXIIIa covalently crosslinks the fibrin clot and represents a promising target for drug development to facilitate fibrinolysis. However, no FXIII‐inhibiting compound has entered clinical trials. Here, we introduce the features of a peptidomimetic inhibitor of FXIIIa (ZED3197) as a potential drug candidate. Methods The potency of ZED3197 against FXIIIa and the selectivity against other human transglutaminases were characterized using transamidation and isopeptidase assays. The inhibition of fibrin crosslinking was evaluated by biochemical methods and thromboelastometry. Further, the pharmacology of the compound was explored in a rabbit model of venous stasis and reperfusion. Results ZED3197 proved to be a potent and selective inhibitor of human FXIIIa. Further, the compound showed broad inhibitory activity against cellular FXIIIA from various animal species. Rotational thromboelastometry in whole human blood indicated that the inhibitor, in a dose‐dependent manner, prolonged clot formation, reduced clot firmness, and facilitated clot lysis without affecting the clotting time, indicating minimal impact on hemostasis. In vivo, the novel FXIIIa inhibitor effectively decreased the weight of clots and facilitated flow restoration without prolongation of the bleeding time. Conclusions ZED3197 is the first drug‐like potent compound targeting FXIIIa, a yet untapped target in anticoagulation. Due to the function of FXIII downstream of thrombin the approach provides minimal impact on hemostasis. In vivo data imply that the inhibitor dissociates an antithrombotic effect from increased bleeding tendency.

Tissue transglutaminase (TG2) catalyzed glutamine deamidation within gluten peptides plays a major role in the pathogenesis of celiac disease. Recent studies reported gliadin deamidation by microbial transglutaminase (MTG) and hypothesize an impact on celiac disease incidence. We therefore investigated deamidation and transamidation activities of MTG and human TG2 based on a wheat gliadin peptide containing an immunodominant epitope for celiac disease. Deamidation activity of MTG was about a magnitude lower than transamidation with a maximum at pH 5 and decreasing values at neutral and basic pH. In contrast, TG2-deamidation reaction rate doubled from pH 6 to pH 7. Transamidation activity of MTG showed minor pH dependence, whereas for TG2 it strongly increased from pH 6 to 7 by a factor of 7.5. Additionally, deamidation by TG2 in the presence of a fivefold excess of amine substrate was observed for reactions at pH 6 at an equal rate to transamidation, while at neutral pH no deamidation occurred. MTG only catalyzed deamidation in addition to transamidation when the substrate ratio was below a 2.5 fold excess of amine. In conclusion, transamidation activity rates of MTG and TG2 were higher compared to deamidation rates. In contrast to TG2, MTG shows a strong and pH-independent transamidation preference.

The successful synthesis and solid state NMR characterization of silica-based organic-inorganic hybrid materials is presented. For this, collagen-like peptides are immobilized on carboxylate functionalized mesoporous silica (COOH/SiOx) materials. A pre-activation of the silica material with TSTU (O-(N-Succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate) is performed to enable a covalent binding of the peptides to the linker. The success of the covalent immobilization is indicated by the decrease of the (13)C CP-MAS NMR signal of the TSTU moiety. A qualitative distinction between covalently bound and adsorbed peptide is feasible by (15)N CP-MAS Dynamic Nuclear Polarization (DNP). The low-field shift of the (15)N signal of the peptide's N-terminus clearly identifies it as the binding site. The DNP enhancement allows the probing of natural abundance (15)N nuclei, rendering expensive labeling of peptides unnecessary.

Introduction The A-subunit of blood coagulation factor XIII is a pro-transglutaminase, which cross-links α- and γ-fibrin-chains in its activated form. Selective inhibitors against FXIII-A may be desirable drugs to prevent the development of thromboses. Animal models are generally used for proof of principle and for toxicological studies in drug development. The aim of the study was to investigate the specificity of a set of FXIII-A-blockers against FXIII-A from different species, i.e. human, dog, mouse, rat and pig. Thus the usefulness of different animal species for FXIII-A-blocker drug development should be evaluated. Materials and Methods FXIII-A proteins were recombinantly produced in insect cells and purified to homogeneity. They were characterized by SDS- and native PAGE, a transamidase assay and isopeptidase assay. The inhibition second-order rate constants of different irreversible inhibitors were determined using the isopeptidase assay. Results All FXIII-A species were able to assemble with recombinant human FXIII-B into a heterotetrameric complex. Kinetic parameters of FXIII-A species were determined. Second-order rate constants for FXIII-A inhibition by two irreversible inhibitors were determined and differed considerably. FXIII-A species of dog, mouse and rat were inhibited in a manner similar to human FXIII-A. Pig FXIII-A however was resistant to a previously described non-peptidic inhibitor. Furthermore, the results showed considerably better inhibition with the novel peptide-based inhibitor compared to the non-peptidic compound. Conclusions Our data shows that biochemical interspecies comparison studies are a prerequisite for animal studies. Peptide-derived inhibitors carrying a Michael Acceptor Pharmacophore (MAP) are a promising new class of FXIII-A-inhibitors.

To our publication “Microbial Transglutaminase Used in Bread Preparation at Standard Bakery Concentrations Does Not Increase Immunodetectable Amounts of Deamidated Gliadin" in Journal of Agricultural and Food Chemistry 2017 Aug 16;65(32):6982-6990 we received a comment by Calderon de la Barca an Sigala-Robles. Essentially the authors question the sense of analyzing MTG-treated bread in relation to celiac disease (because celiac patients do not eat bread) and also the technique of Western blotting we applied. In this response we point out that in the context of circulating hypotheses on a potential celiac disease triggering effect of MTG-treated bread in addition to diagnosed celiac patients two further groups have to be considered: non-diagnosed celiacs as well as genetically predisposed individuals. Both groups are not following gluten free diets. Further, we explain the advantage of Western blotting compared to ELISA in order to reveal any activity of MTG on gluten at standard bakery and magnitudes high...

Up till now scholarship has assumed that the return of Hercules from the underworld at the end of the second act of Hercules Furens is prefigured in some kind of epiphany (Her. F. 520-3). In the course of the drama, however, it is expressly stated on two occasions that Hercules has already left the underworld at an earlier point. This apparent contradiction can be resolved if one supposes that Amphitryon, who is the sole witness of the epiphany, is the victim of an illusion. It is possible to explain the phenomena which he interprets wrongly (the groaning of the earth and the swaying of the temple) by taking into account the simultaneous action on stage.

The paper compares the mineralogy and fabric of two Tunisian phosphorite deposits, which have been formed during the late Palaeocene and early Eocene as part of the large, 6000 km long “North African Phosphorite Belt”. The deposits Kefschwaier (Metlaoui Region) and Sra Ouertane are situated south resp. north of the Tertiary “Ile de Kasserine”. While the southern deposit Kefschwaier is characterised by several metastable and weak mineral phases (additional to francolite, calcite, quartz and some “normal” clay minerals like illite and kaolinite), e.g. opal- CT, chalcedony, (Cu-) Fe-sulfides and Mg-silicates (palygorskite, sepiolite), these minerals are absent in Sra Ouertane. There, the former francolite ooids are deformed and the fossil relics are mainly broken and recrystallised, and several authigenic minerals (e.g. Fe-dolomite, albite, K-feldspar, montmorillonite) have been newly formed. The observed differences in mineralogy and fabric are interpreted as caused by the influence of low-grade regional metamorphism which has occurred during the orogenesis of the nearby Atlas mountains and the associated processes of salt diapirism in the Atlas foreland.

Bellum civile 6,564-569 describes how the witch Erictho disrupts a funeral. In its context the expression cognato in funere refers not to any putative relatives of Erictho (not mentioned elsewhere) or to relatives of some anonymous deceased person (so Korenjak), but to the only group of people Erictho shares some kind of bond with, namely her ‚sisters‘ the Thessalian witches.

Intestinal electroneutral NaCl absorption is mediated by parallel operation of Na(+)/H(+) and Cl(-)/HCO(3)(-) exchange in the enterocyte apical membrane. The ion transporters involved are Na(+)/H(+) exchanger 3 (NHE3) and the down regulated in adenoma (dra) gene product. cAMP-mediated inhibition of NHE3 requires the transporter to bind to the second PDZ (PSD95, disk large, ZO1) domain of the adapter protein NHE3 kinase A regulatory protein (E3KARP). Because the C-terminal four amino acids of dra are ETKF (glutamate-threonine-lysine-phenylalanine), resembling a PDZ interaction motif, we hypothesized that dra may also bind to one of the PDZ domains of E3KARP. In vitro the ETKF motif of dra binds to the second PDZ domain of E3KARP, the affinity being comparable to that of the known ligand CFTR. The C-terminal phenylalanine, which is an unconventional residue in PDZ interaction motifs, can only be substituted by the classical residue leucine, but not by other hydrophobic residues (valine, isoleucine). Immunofluorescence colocalizes dra, NHE3, and E3KARP in the apical compartment of human proximal colon. We suggest a model in which both NHE3 and dra bind to the second PDZ domain of E3KARP and that linking of the transporters occurs through dimerization of E3KARP. In such a model, the first PDZ domain would remain available for instance for signal transduction proteins.