Drug hypersensitivity involves the activation of T cells in an HLA allele–restricted manner. Because the majority of individuals who carry HLA risk alleles do not develop hypersensitivity, other parameters must control development of the drug-specific T cell response. Thus, we have used a T cell–priming assay and nitroso sulfamethoxazole (SMX-NO) as a model Ag to investigate the activation of specific TCR Vβ subtypes, the impact of programmed death -1 (PD-1), CTL-associated protein 4 (CTLA4), and T cell Ig and mucin domain protein-3 (TIM-3) coinhibitory signaling on activation of naive and memory T cells, and the ability of regulatory T cells (Tregs) to prevent responses. An expansion of the TCR repertoire was observed for nine Vβ subtypes, whereas spectratyping revealed that SMX-NO–specific T cell responses are controlled by public TCRs present in all individuals alongside private TCR repertoires specific to each individual. We proceeded to evaluate the extent to which the activation of these TCR Vβ–restricted Ag-specific T cell responses is governed by regulatory signals. Blockade of PD-L1/CTLA4 signaling dampened activation of SMX-NO–specific naive and memory T cells, whereas blockade of TIM-3 produced no effect. Programmed death-1, CTLA4, and TIM-3 displayed discrete expression profiles during drug-induced T cell activation, and expression of each receptor was enhanced on dividing T cells. Because these receptors are also expressed on Tregs, Treg-mediated suppression of SMX-NO–induced T cell activation was investigated. Tregs significantly dampened the priming of T cells. In conclusion, our findings demonstrate that distinct TCR Vβ subtypes, dysregulation of coinhibitory signaling pathways, and dysfunctional Tregs may influence predisposition to hypersensitivity.
The dynamic development of computer and software technology in recent years was accompanied by the expansion and widespread implementation of artificial intelligence (AI) based methods in many aspects of human life. A prominent field where rapid progress was observed are high‐throughput methods in biology that generate big amounts of data that need to be processed and analyzed. Therefore, AI methods are more and more applied in the biomedical field, among others for RNA‐protein binding sites prediction, DNA sequence function prediction, protein‐protein interaction prediction, or biomedical image classification. Stem cells are widely used in biomedical research, e.g., leukemia or other disease studies. Our proposed approach of
... Show MoreBackground: Behçet’s disease (BD) is a disorder of systemic inflammatory condition. Its important features are represented by recurrent oral, genital ulcerations and eye lesions. Aims. The purpose of the current study was to evaluate and compare cytological changes using morphometric analysis of the exfoliated buccal mucosal cells in Behçet’s disease patients and healthy controls, and to evaluate the clinical characteristics of Behçet’s disease. Methods. Twenty five Behçet’s disease patients have been compared to 25 healthy volunteers as a control group. Papanicolaou stain was used for staining the smears taken from buccal epithelial cells to be analyzed cytomorphometrically. The image analysis sof
... Show MoreThe present study was designed to investigate the possibility of exploiting the interspecies interaction of microbial cells in order to enhance the production of prodigiosin by local isolate S. marcescens S23. Prodigiosin is a promising drug owing to its characteristics of antibacterial, antifungal, immunosuppressive and anticancer activities. S. marcescens S23 was isolated from soil sample and already recognized via morphological, biochemical and molecular identification process. The first step was to detect the optimal conditions for maximum prodigiosin production using chemically defined liquid medium. The results revealed that the optimal conditions for prodigiosin production were sucrose as carbon source; peptone as nitrogen source;
... Show MoreDesign system often generated relationship within the frame work of their concept of interior design a system or more can be created between design relationships within this concept in the structure of its internal space product. Through the division of all to it parts to reveal the hidden places and stages of composition and their relationship and interdependence between them. And then re- composition of all its parts, doth in the deign process at the initial stages or in the processes of treatments that are necessary after the completion of design and circulation. To be able to use other events close to the first events designed for them. In terms of idea logical in fluency and its social, economic, cultural and political dimension. As
... Show MoreMany behavioral researchers pointed out the importance of relaxation techniques in the treatment of different psychological disorders where find the importance of these techniques in reducing anxiety and stress and the resulted of behaviors and habits, with the development of these techniques are being used to gain public health, whether mental health or physical or mentality, and one of these techniques is music therapy that reduces tension and anxiety and operates a state of relaxation, which is used in the treatment of patients of dental clinic.
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... Show MoreIn this paper we study the effect of the number of training samples for Artificial neural networks ( ANN ) which is necessary for training process of feed forward neural network .Also we design 5 Ann's and train 41 Ann's which illustrate how good the training samples that represent the actual function for Ann's.
10 sites were selected for investigating zebra mussels in the Tigris River for the study that was conducted for the period from January to December 2020. The results of this investigation showed that zebra mussels were recorded in the Tigris at Taji on sites 7, 8, 9 and 10, while it was not found in the Tigris at Kut on sites 1, 2, 3, 4, 5 and 6. This is the first time that this species was ever recorded in the Tigris. It was found that the sites where zebra mussels appeared had a clear impact on the decrease in the total organic carbon %age and turbidity (NTU). High dissolved oxygen values were observed in the sites where zebra mussels were recorded, and the appearance of zebra mussels in these sites caused a clear decrease in
... Show MoreThe Impact of Intellectual trends on the nature of the Economic Structure of Iraq
In this work, the effect of atomic ratio on structural and optical properties of SnO2/In2O3 thin films prepared by pulsed laser deposition technique under vacuum and annealed at 573K in air has been studied. Atomic ratios from 0 to 100% have been used. X-ray diffraction analysis has been utilized to study the effect of atomic ratios on the phase change using XRD analyzer and the crystalline size and the lattice strain using Williamson-Hall relationship. It has been found that the ratio of 50% has the lowest crystallite size, which corresponds to the highest strain in the lattice. The energy gap has increased as the atomic ratio of indium oxide increased.