Improved MSTID modelling and impact on precise GNSS processing

Peer ReviewedPreprin

A Universal Approach to Eliminate Antigenic Properties of Alpha-Gliadin Peptides in Celiac Disease

Celiac disease is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins, including the α-gliadins. It has been shown that α-gliadins harbor several major epitopes involved in the disease pathogenesis. A major step towards elimination of gluten toxicity for celiac disease patients would thus be the elimination of such epitopes from α-gliadins. We have analyzed over 3,000 expressed α-gliadin sequences from 11 bread wheat cultivars to determine whether they encode for peptides potentially involved in celiac disease. All identified epitope variants were synthesized as peptides and tested for binding to the disease-associated HLA-DQ2 and HLA-DQ8 molecules and for recognition by patient-derived α-gliadin specific T cell clones. Several specific naturally occurring amino acid substitutions were identified for each of the α-gliadin derived peptides involved in celiac disease that eliminate the antigenic properties of the epitope variants. Finally, we provide proof of principle at the peptide level that through the systematic introduction of such naturally occurring variations α-gliadins genes can be generated that no longer encode antigenic peptides. This forms a crucial step in the development of strategies to modify gluten genes in wheat so that it becomes safe for celiac disease patients. It also provides the information to design and introduce safe gluten genes in other cereals, which would exhibit improved quality while remaining safe for consumption by celiac disease patients

Direct MSTID mitigation in precise GPS processing

This is the peer reviewed version of the following article: Hernandez, M., Wielgosz, P., Paziewski, J., Krypiak-Gregorczyk, A., Krukowska, M., Stepniak, K., Kaplon, J., Hadas, T., Sosnica, K., Bosy, J., Orús, R., Monte, E., Yang, H., Garcia-Rigo, A., Olivares-Pulido, G. Direct MSTID mitigation in precise GPS processing. "Radio science", Març 2017, vol. 52, núm. 3, p. 321-337, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/2016RS006159/abstract. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-ArchivingIn this paper, the authors summarize a simple and efficient approach developed to mitigate the problem in precise GNSS positioning originated by the most frequent ionospheric wave signatures: the Medium Scale Travelling Ionospheric Disturbances (MSTIDs). The direct GNSS Ionospheric Interferometry technique (hereinafter dGII), presented in this paper, is applied for correcting MSTID effects on precise Real Time Kinematic (RTK) and tropospheric determination. It consists of the evolution of the former climatic Differential Delay Mitigation Model for MSTIDs (DMTID), for real-time conditions, using ionospheric data from a single permanent receiver only. The performance is demonstrated with networks of GNSS receivers in Poland, treated as users under real-time conditions, during two representative days in winter and summer seasons (days 353 and 168 of year 2013). In range domain, dGII typically reduces the ionospheric delay error up to 10-90% of the value when the MSTID mitigation model is not applied. The main dGII impact on precise positioning is that we can obtain reliable RTK position faster. In particular the ASR (ambiguity success rate) parameter increases, from 74% to 83%, with respect to the original uncorrected observations. The average of time to first fix is shortened from 30s to 13s. The improvement in troposphere estimaton, due to any potential impact of the MSTID mitigation model, was most difficult to demonstrate.Peer ReviewedPostprint (author's final draft

Violent aggression predicted by multiple pre-adult environmental hits

Early exposure to negative environmental impact shapes individual behavior and potentially contributes to any mental disease. We reported previously that accumulated environmental risk markedly decreases age at schizophrenia onset. Follow-up of matched extreme group individuals (≤1 vs. ≥3 risks) unexpectedly revealed that high-risk subjects had >5 times greater probability of forensic hospitalization. In line with longstanding sociological theories, we hypothesized that risk accumulation before adulthood induces violent aggression and criminal conduct, independent of mental illness. We determined in 6 independent cohorts (4 schizophrenia and 2 general population samples) pre-adult risk exposure, comprising urbanicity, migration, physical and sexual abuse as primary, and cannabis or alcohol as secondary hits. All single hits by themselves were marginally associated with higher violent aggression. Most strikingly, however, their accumulation strongly predicted violent aggression (odds ratio 10.5). An epigenome-wide association scan to detect differential methylation of blood-derived DNA of selected extreme group individuals yielded overall negative results. Conversely, determination in peripheral blood mononuclear cells of histone-deacetylase1 mRNA as 'umbrella mediator' of epigenetic processes revealed an increase in the high-risk group, suggesting lasting epigenetic alterations. Together, we provide sound evidence of a disease-independent unfortunate relationship between well-defined pre-adult environmental hits and violent aggression, calling for more efficient prevention

Correction: Iwan et al. Pro-Oxidative Effect of KIO3 and Protective Effect of Melatonin in the Thyroid—Comparison to Other Tissues. Life 2021, 11, 592

In the original article [...]</jats:p

Pro-Oxidative Effect of KIO3 and Protective Effect of Melatonin in the Thyroid—Comparison to Other Tissues

Not only iodine deficiency, but also its excess may contribute to thyroid cancer. Potassium iodate (KIO3), which is broadly used in the salt iodization program, can increase oxidative damage to membrane lipids (lipid peroxidation, LPO) under experimental conditions, with the strongest damaging effect at KIO3 concentration of ~10 mM (corresponding to physiological iodine concentration in the thyroid). Melatonin is an effective antioxidant, which protects against KIO3-induced LPO in the thyroid. This study aimed to compare the protective effects of melatonin, used in the highest achievable in vitro concentration, against KIO3-induced oxidative damage to membrane lipids in various porcine tissues (thyroid, ovary, liver, kidney, brain, spleen, and small intestine). Homogenates were incubated in the presence of KIO3 (20; 15; 10; 7.5; 5.0; 0.0 mM) without/with melatonin (5 mM). The malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. KIO3 increased the LPO in all examined tissues; in the thyroid, the damaging effect of KIO3 (10; and 7.5 mM) was lower than in other tissues and was not observed for the lowest concentration of 5 mM. Melatonin reduced LPO induced by KIO3 (10, 7.5, and 5 mM) in all tissues, and in the thyroid it was also protective against as high a concentration of KIO3 as 15 mM; the LPO level resulting from KIO3 + melatonin treatment was lower in the thyroid than in other tissues. In conclusion, the thyroid is less sensitive tothe pro-oxidative effects of KIO3 compared to other tissues. The strongest protective effect of melatonin was observed in the thyroid, but beneficial effects were significant also in other tissues. Melatonin should be considered to avoid the potential damaging effects of iodine compounds applied in iodine prophylaxis.</jats:p

Correction: Iwan et al. Pro-Oxidative Effect of KIO3 and Protective Effect of Melatonin in the Thyroid&mdash;Comparison to Other Tissues. Life 2021, 11, 592

In the original article [...