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

Objectively measured and self-reported leisure-time sedentary behavior and academic performance in youth: The UP&DOWN Study

The objective of this study was to examine the associations of objectively measured and self-reported sedentary behavior during leisure time with academic performance and patterns of sedentary behavior with academic performance. This study was conducted with 1146 youth aged 12.5 ± 2.5 years in Spain during 2011–2012. Leisure-time sedentary behavior during out-of-school hours was assessed by accelerometry and self-report. Academic performance was assessed through school grades.Evaluación de la interacción entre genética y actividad física en el estado físico y la salud en escolares y adolescentes con Síndrome de Down: estudio de seguimiento a tres años Plan Nacional de I+D+i. Ministerio de Ciencia e Innovación (Ref. DEP2010-21662-C04-02).2.893 JCR (2015) Q1, 24/151 Medicine, general & internal, 34/172 Public, environmental & occupational healthUE