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.
Influence of metal nanoparticles synthesized by microorganisms upon soil-borne microscopic fungus Aspergillus terreus K-8 was studied. It was established that the metal nanoparticles synthesized by microorganisms affect the enzymatic activity of the studied culture. Silver nanoparticles lead to a decrease in cellulase activity and completely suppress the amylase activity of the fungus, while copper nanoparticles completely inhibit the activity of both the cellulase complex and amylase. The obtained results imply that the large-scale use of silver and copper nanoparticles may disrupt biological processes in the soil and cause change in the physiological and biochemical state of soil-borne microorganisms as well.
This study investigates the impact of varying glass fiber-reinforced polymer (GFRP) stirrup spacing on the performance of doubly GFRP-reinforced concrete beams. The research focuses on assessing the behavior of GFRP-reinforced concrete beams, including load-carrying capacity, cracking, and deformability. It explores the feasibility and effectiveness of GFRP bars as an alternative to traditional steel reinforcement in concrete structures. Six concrete beams with a cross-section of 300 mm (wide) × 250 mm (deep), simply supported on a 2100 mm span, were tested. The beams underwent four-point bending with two concentrated loads applied symmetrically at one-third of the span length, resulting in a shear span (a)-to-depth (h) ratio of 2.
... Show MoreBackground: Dental caries is generally given the highest priority in national oral health services for adult populations. Yet, there is no study which has explored the impact on quality of life specifically related to dental caries in samples of dental students. The purpose of the current study was to assess the impact of caries experience on quality of life among dental students in three governorates in Iraq. Materials and Methods: This observational study included 1364 dental students aged 18–22 years old, from three governorates. Information on quality of life was obtained from a structured, self-administered questionnaire from the students who were willing to participate in the study. The data was collected, summarized and sta
... Show MoreThe objective of this study is to determine the efficacy of class V Er:YAG laser (2940 nm) cavity preparation and conventional bur cavity preparation regarding Intrapulpal temperature rise during cavity preparation in extracted human premolar teeth. Twenty non carious premolar teeth extracted for orthodontic purposes were used and class V cavity preparation was applied both buccal and lingual sides for each tooth .Samples were equally grouped into two major groups according to cavity depth (1mm and 2mm). Each major group was further subdivided into two subgroupsof ten teeth for each (twenty cavities for each subgroup). TwinlightEr:YAG laser (2940 nm) with 500mJ pulse energy, P.R.R of 10 Hz and 63.69 J/cm2 energy density was used. The ana
... Show MoreThe food web is a crucial conceptual tool for understanding the dynamics of energy transfer in an ecosystem, as well as the feeding relationships among species within a community. It also reveals species interactions and community structure. As a result, an ecological food web system with two predators competing for prey while experiencing fear was developed and studied. The properties of the solution of the system were determined, and all potential equilibrium points were identified. The dynamic behavior in their immediate surroundings was examined both locally and globally. The system’s persistence demands were calculated, and all conceivable forms of local bifurcations were investigated. With the aid of MATLAB, a numerical simu
... Show MoreYucca gloriosa Variegata L. is a stemless. The whole plant of Y. gloriosa L. has vast medicinal uses. TheNative Americans and North New Mexico used a tea from the leaves and roots to treat asthma, headache,wound healing. As well as it was being consumed as daily dietary. All part of Y. gloriosa L. is rich in saponinsteroidal glycosides. Saponin extracts are well-known to be highly toxic. Hence, present study was carriedout to investigate the toxicity of saponin and estimate the LD50 value which helps in determining the safedose range for the drug that be used, as well as to determine hematological aspects and examine histologicaleffect. Different concentrations of saponin extract were injected into male mice (10,000, 8000, 6000, 400
... Show MoreAccurate description of thermodynamic, structural, and electronic properties for bulk and surfaces of ceria (CeO2) necessitates the inclusion of the Hubbard parameter (U) in the density functional theory (DFT) calculations to precisely account for the strongly correlated 4f electrons. Such treatment is a daunting task when attempting to draw a potential energy surface for CeO2-catalyzed reaction. This is due to the inconsistent change in thermo-kinetics parameters of the reaction in reference to the variation in the U values. As an illustrative example, we investigate herein the discrepancy in activation and reaction energies for steps underlying the partial and full hydrogenation of acetyl
... Show MoreThe impact of applying the K-W-L self-scheduling technique on first-year intermediate students' learning of basic volleyball skills, Ayad Ali Hussein*, Israa Fouad Salih
Background: The marginal adaptation has a key role in the success and longevity of the fixed dental restoration, which is affected by the impression and the fabrication techniques .The objective of this in vitro study was to evaluate and compare the marginal fitness of lithium disilicate crowns using two different digital impression techniques (direct and indirect techniques) and two different fabrication techniques (CAD/CAM and Press techniques). Materials and Methods: Thirty two sound upper first premolar teeth of comparable size extracted for orthodontic reason were selected in this study .Standardized preparation of all teeth samples were carried out with modified dental surveyor to receive all ceramic crown restoration with 1 mm deep
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