The Occurrence of Antibodies Against Gluten in Children with Autism Spectrum Disorders Does Not Correlate with Serological Markers of Impaired Intestinal Permeability

Jan Jozefczuk,Ewa Konopka,Joanna Beata Bier1a,Ilona Trojanowska,Agnieszka Sowin´ska,Rafa1 Czarnecki,Lucjan Sobol,Pawe1 Jo´zefczuk,Weronika Surd,Bo_zena Cukrowska 한국식품영양과학회 2018 Journal of medicinal food Vol.21 No.2

There is evidence that children with autism spectrum disorders (ASDs) display an increased immune reactivity against gluten, which is supposed to be the effect of intestinal barrier abnormalities. The aim of study was to evaluate the relation of antibody induced by gluten to zonulin and intestinal fatty acid binding proteins (I-FABP), that is, serological markers of an impaired gut barrier. The study included 77 patients with ASDs. Zonulin, I-FABP, celiac-specific antibodies, anti-gliadin antibodies (AGA), and antibodies against neural transglutaminase 6 (TG6) of immunoglobulin (Ig) A and IgG classes were detected in sera. Celiac-specific antibodies were negative in all ASD children, four children (5.2%) had positive anti-TG6 antibodies, and increased AGA-IgG production was found in 21 patients (27.3%). Mean levels of zonulin and I-FABP in ASD patients were similar to those found in healthy controls and revealed a negative correlation with age, whereas regression analysis revealed a significant positive relationship between antibody production and the age. Serum concentrations of zonulin and I-FABP showed no statistically significant association with antibody positivity. An increased production of antibodies related to gliadin and neural TG6 in ASD children is not related to serological markers of an impaired intestinal barrier.

The robust calibration of a structural-default model with jumps

Andre Biere,Matthias Scherer 인하대학교 정석물류통상연구원 2009 인하대학교 정석물류통상연구원 학술대회 Vol.2009 No.10

CDS calibration routines for a structural-default model with discontinuous firm-value process, modeled as the exponential of jump diffusion with two-sided exponentially distributed jumps, are developed. The required default probabilities are computed by inverting the Laplace transform of first-passage probabilities. Four Laplace-inversion algorithms are examined for the given problem with respect to precision and run-time; these are based on different theoretical inversion formulas. Then it is demonstrated that the model explains CDS spreads of various firms with high precision. The calibration algorithm is further refined to a robust routine that penalizes deviations from a given prior, which is inspired by the relative entropy of two probability measures. It is shown that, if the model is calibrated at consecutive days, stable model parameters can be obtained with pricing errors below bid-ask spreads.

dHIP14-dependent palmitoylation promotes secretion of the BMP antagonist Sog

Kang, K.H.,Bier, E. Academic Press 2010 Developmental Biology Vol.346 No.1

Analysis of diverse signaling systems has revealed that one important level of control is regulation of membrane trafficking of ligands and receptors. The activities of some ligands are also regulated by whether they are membrane bound or secreted. In Drosophila, several morphogenetic signals that play critical roles in development have been found to be subject to such regulation. For example, activity of the Hedgehog (Hh) is regulated by Raspberry, which palmitoylates Hh. Similarly, the palmitoylases Porcupine and Raspberry increase the activities of Wingless (Wg) and the EGF-ligand Spitz (Spi), respectively. In contrast to its vertebrate homologues, which have typical N-terminal signal sequences, the precursor form of Drosophila Hh contains an internal type-II secretory signal motif. The Short Gastrulation (Sog) protein is another secreted Drosophila protein that contains a type-II signal and differs from its vertebrate ortholog Chordin which contains a standard signal peptide. In this study, we examine the regulation of Sog secretion and regulation by dHIP14, the ortholog of a mammalian palmitoylase first identified as Huntington Interacting Protein (HIP). We show that dHIP14 binds to Sog and that Sog is palmitoylated. In S2 cells, dHIP14 promotes secretion of Sog as well as stabilizing a membrane associated form of Sog. We examined the requirement for candidate cysteine residues in the N-terminal predicted cytoplasmic domain of Sog and find that Cys27, one of two adjacent cysteines (Cys27 and Cys28), is essential for the full activity of dHIP14 and its effect on Sog. Finally, we find that dHIP14 promotes the activity of Sog in vivo. These studies highlight the growing importance of lipid modification in regulating signaling at the level of ligand production and localization.

Production of functional antibody fragments in a vesicle-based eukaryotic cell-free translation system

Stech, M.,Merk, H.,Schenk, J.A.,Stocklein, W.F.M.,Wustenhagen, D.A.,Micheel, B.,Duschl, C.,Bier, F.F.,Kubick, S. Elsevier Science Publishers 2013 Journal of biotechnology Vol.164 No.2

Cell-free protein synthesis is of increasing interest for the rapid and high-throughput synthesis of many proteins, in particular also antibody fragments. In this study, we present a novel strategy for the production of single chain antibody fragments (scFv) in a eukaryotic in vitro translation system. This strategy comprises the cell-free expression, isolation and label-free interaction analysis of a model antibody fragment synthesized in two differently prepared insect cell lysates. These lysates contain translocationally active microsomal structures derived from the endoplasmic reticulum (ER), allowing for posttranslational modifications of cell-free synthesized proteins. Both types of these insect cell lysates enable the synthesis and translocation of scFv into ER-derived vesicles. However, only the one that has a specifically adapted redox potential yields functional active antibody fragments. We have developed a new methodology for the isolation of functional target proteins based on the translocation of cell-free produced scFv into microsomal structures and subsequent collection of protein-enriched vesicles. Antibody fragments that have been released from these vesicles are shown to be well suited for label-free binding studies. Altogether, these results show the potential of insect cell lysates for the production, purification and selection of antibody fragments in an easy-to-handle and time-saving manner.

Outcome of endodontic treatments performed by Brazilian undergraduate students: 3- to 8-year follow up

da Rocha Jéssica Gabriele,Lena Isabella Marian,Trindade Jéssica Lopes,Liedke Gabriela Salatino,Morgental Renata Dornelles,Bier Carlos Alexandre Souza 대한치과보존학회 2022 Restorative Dentistry & Endodontics Vol.47 No.3

Objectives This study aimed to evaluate the success rate of endodontic treatments performed by undergraduate students and the factors associated with the outcome. Materials and Methods A follow-up of 3 to 8 years after root canal filling was carried out in 91 patients. At the follow-up visits, medical and dental history questionnaires were applied along with clinical and radiographic examinations. Data collected in the clinical exam included: the presence of pain, swelling, sinus tract, mobility, tenderness to palpation and percussion, periodontal probing profile, and type/quality of coronal restoration. Postoperative and follow-up radiographs were digitalized and analyzed by 2 trained and calibrated examiners to assess periapical healing. The treatment outcome was based on strict clinical and radiographic criteria and classified as success (absence of any clinical and radiographic sign of apical periodontitis) or failure (other combination). Logistic regression was used to investigate the impact of clinical and radiographic variables on endodontic treatment outcomes at a 5% significance level. Results The success rate of endodontic treatments was 60.7%. The only risk factor significantly associated with failure was the presence of a periapical lesion on the postoperative radiograph (odds ratio, 3.35; 95% confidence interval, 1.17–9.54). Conclusions The success rate of endodontic treatments performed by undergraduate students was low and was jeopardized by the presence of a periapical lesion on the postoperative radiograph. Objectives This study aimed to evaluate the success rate of endodontic treatments performed by undergraduate students and the factors associated with the outcome. Materials and Methods A follow-up of 3 to 8 years after root canal filling was carried out in 91 patients. At the follow-up visits, medical and dental history questionnaires were applied along with clinical and radiographic examinations. Data collected in the clinical exam included: the presence of pain, swelling, sinus tract, mobility, tenderness to palpation and percussion, periodontal probing profile, and type/quality of coronal restoration. Postoperative and follow-up radiographs were digitalized and analyzed by 2 trained and calibrated examiners to assess periapical healing. The treatment outcome was based on strict clinical and radiographic criteria and classified as success (absence of any clinical and radiographic sign of apical periodontitis) or failure (other combination). Logistic regression was used to investigate the impact of clinical and radiographic variables on endodontic treatment outcomes at a 5% significance level. Results The success rate of endodontic treatments was 60.7%. The only risk factor significantly associated with failure was the presence of a periapical lesion on the postoperative radiograph (odds ratio, 3.35; 95% confidence interval, 1.17–9.54). Conclusions The success rate of endodontic treatments performed by undergraduate students was low and was jeopardized by the presence of a periapical lesion on the postoperative radiograph.

Sestrin as a Feedback Inhibitor of TOR That Prevents Age-Related Pathologies

Lee, J. H.,Budanov, A. V.,Park, E. J.,Birse, R.,Kim, T. E.,Perkins, G. A.,Ocorr, K.,Ellisman, M. H.,Bodmer, R.,Bier, E.,Karin, M. American Association for the Advancement of Scienc 2010 Science Vol.327 No.5970

<P>Sestrins are conserved proteins that accumulate in cells exposed to stress, potentiate adenosine monophosphate-activated protein kinase (AMPK), and inhibit activation of target of rapamycin (TOR). We show that the abundance of Drosophila sestrin (dSesn) is increased upon chronic TOR activation through accumulation of reactive oxygen species that cause activation of c-Jun amino-terminal kinase and transcription factor Forkhead box O (FoxO). Loss of dSesn resulted in age-associated pathologies including triglyceride accumulation, mitochondrial dysfunction, muscle degeneration, and cardiac malfunction, which were prevented by pharmacological activation of AMPK or inhibition of TOR. Hence, dSesn appears to be a negative feedback regulator of TOR that integrates metabolic and stress inputs and prevents pathologies caused by chronic TOR activation that may result from diminished autophagic clearance of damaged mitochondria, protein aggregates, or lipids.</P>