The aim of the present review is to provide an update of the current research into the pathogenesis of autoimmune diseases associated with 8.1 ancestral haplotype. This is a common Caucasoid ...haplotype carried by most people who type for HLA‐B8, DR3. Numerous genetic studies reported that individuals with certain HLA alleles have a higher risk of specific autoimmune disorders than those without these alleles. However, much remains to be learned about the heritability of autoimmune conditions. Recently, progress and advances in the field of genome‐wide‐association studies have revolutionized the capacity to perform large, economically feasible, and statistically robust analyses of HLA within 8.1 ancestral haplotype, and understand its contribute to autoimmune events.
In this paper, the characteristic features of this haplotype that might give rise to diverse autoimmune phenotypes are reviewed, focusing on the contribution of the HLA‐DRB1 gene, the most polymorphic sequence within the HLA II region.
Summary
T helper 9 (Th9) cells and interleukin (IL)‐9 are involved in the pathogenesis of several autoimmune diseases. The exact role of IL‐9 and Th9 cells in patients with systemic sclerosis (SSc) ...have not yet been studied adequately. IL‐9, IL‐9R, transcription factor PU.1 (PU.1), IL‐4, thymic stromal lymphopoietin (TSLP) and transforming growth factor (TGF)‐β expression were assessed in skin and kidney biopsies of SSc patients and healthy controls (HC) by immunohistochemistry (IHC). The cellular source of IL‐9 was also analysed by confocal microscopy analysis. Peripheral IL‐9‐producing cells were also studied by flow cytometry. The functional relevance of IL‐9 increased expression in SSc was also investigated. Our results demonstrated a strong expression of IL‐9, IL‐9R, IL‐4, TSLP and TGF‐β in skin tissues of patients with both limited and diffuse SSc. IL‐9 expression was observed mainly in the context of skin infiltrating mononuclear cells and keratinizing squamous epithelium. IL‐9 over‐expression was also observed in renal biopsies of patients with SSc. IL‐9 producing cells in the skin were identified as Th9 cells. Similarly, Th9 cells were expanded and were the major source of IL‐9 among SSc peripheral blood mononuclear cells (PBMC), their percentage being correlated directly with the modified Rodnan skin score. Infiltrating mononuclear cells, mast cells and neutrophils expressed IL‐9R. In in‐vitro studies stimulation with rIL‐9 significantly induced NET (neutrophil extracellular traps) release by dying cells (NETosis) in neutrophils, expansion of mast cells and increase of anti‐systemic scleroderma 70 (Scl70) production by B cells. Our findings suggest that Th9 cells and IL‐9 could be implicated in the pathogenesis of SSc.
IL‐9 and Th9 cells are expanded in the skin, kidney and peripheral blood of SSc patients.
IL‐9 pathway may play an important role in SSc and should be considered as potential therapeutic target in SSc.
We construct square and target patterns solutions of the FitzHugh–Nagumo reaction–diffusion system on planar bounded domains. We study the existence and stability of stationary square and ...super-square patterns by performing a close to equilibrium asymptotic weakly nonlinear expansion: the emergence of these patterns is shown to occur when the bifurcation takes place through a multiplicity-two eigenvalue without resonance. The system is also shown to support the formation of axisymmetric target patterns whose amplitude equation is derived close to the bifurcation threshold. We present several numerical simulations validating the theoretical results.
In this article the authors discuss the effect of different fuel ratios on the performance and pollutant fractions of a common rail diesel engine supplied with both natural gas and diesel oil. The ...study of the dual fuel NG/diesel operation is carried out on a CFD basis, with an engine numerical simulation that includes the gas exchange periods and it aims at a comprehensive analysis of both the combustion development and the pollutant formation under different conditions induced by different choices of the operating parameters and fuel. Preliminary calculations have been performed to individuate the correct setting of some injection models, in order to determine the most appropriate setup of the injection timing when varying the CNG ratio in the fuel blend.
The calculations are compared with some experimental data obtained on a light duty direct injection diesel engine at steady state test bench. In particular, a comparison between diesel and dual fuel diesel/CNG operation has been made, in terms of performance and pollutant levels.
•The attention is focused on the response of a diesel engine supplied with methane and diesel oil.•The experimental tests provide confirmation of the CFD based analysis and put into evidence additional problems.•Both CFD and experiments highlight that the combustion is activated by the pilot injection of the diesel oil.•The best compromise in terms of pollutant and CO2 control is obtained at nearly 50% of CH4 ratio.•Higher CH4 ratios (>75%) lead to conditions close to knocking and to a relevant increase of nitric oxides.
Cystic echinococcosis is a zoonotic disease caused by the larval stage of the parasite Echinococcus granulosus sensu lato. The available anti-parasitic treatment is mostly limited to a continuous ...administration of albendazole. However, due to its numerous side-effects and efficacy of around 50%, there is a need to find new drugs to improve the treatment for this disease. In the current study, the in vitro and in vivo efficacy of a Stevia multiaristata extract against E. granulosus sensu stricto (s.s.) was demonstrated. Stevia multiaristata extract (100 and 50 μg mL−1) caused a quick viability decrease on protoscoleces which was consistent with the observed tegumental alterations. Loss of turgidity was detected in 95 ± 3.4% of cysts incubated with S. multiaristata extract during 2 days (100 μg mL−1) and the collapse of the germinal layer was observed in 60 ± 9.3% of cysts treated with 100 μg mL−1 of the S. multiaristata extract during 4 days. The half maximal effective concentration value was 69.6 μg mL−1 and the selectivity index for E. granulosus s.s. cysts was 1.9. In this clinical efficacy study, the treatment of infected mice with the S. multiaristata extract (50 mg kg−1) caused a significant decrease in the weight of the cysts compared with the control group. These results coincided with the tissue damage observed in the cysts at the ultrastructural level. In conclusion, we observed high protoscolicidal and cysticidal effects, and significant reduction in the weight of the cysts in experimentally infected mice following treatment with the S. multiaristata extract.
In this paper, we shall study the formation of stationary patterns for a reaction-diffusion system in which the FitzHugh-Nagumo (FHN) kinetics, in its excitable regime, is coupled to linear ...cross-diffusion terms. In (Gambino et al. in Excitable Fitzhugh-Nagumo model with cross-diffusion: long-range activation instabilities, 2023), we proved that the model supports the emergence of cross-Turing patterns, i.e., close-to-equilibrium structures occurring as an effect of cross-diffusion. Here, we shall construct the cross-Turing patterns close to equilibrium on 1-D and 2-D rectangular domains. Through this analysis, we shall show that the species are out-of-phase spatially distributed and derive the amplitude equations that govern the pattern dynamics close to criticality. Moreover, we shall classify the bifurcation in the parameter space, distinguishing between super-and sub-critical transitions. In the final part of the paper, we shall numerically investigate the impact of the cross-diffusion terms on large-amplitude pulse-like solutions existing outside the cross-Turing regime, showing their emergence also in the case of
lateral activation
and
short-range inhibition
.
In this paper, we shall study a spatially extended version of the FitzHugh-Nagumo model, where one describes the motion of the species through cross-diffusion. The motivation comes from modeling ...biological species where reciprocal interaction influences spatial movement. We shall focus our analysis on the excitable regime of the system. In this case, we shall see how cross-diffusion terms can destabilize uniform equilibrium, allowing for the formation of close-to-equilibrium patterns; the species are out-of-phase spatially distributed, namely high concentration areas of one species correspond to a low density of the other (cross-Turing patterns). Moreover, depending on the magnitude of the inhibitor’s cross-diffusion, the pattern’s development can proceed in either case of the inhibitor/activator diffusivity ratio being higher or smaller than unity. This allows for spatial segregation of the species in both cases of
short-range activation/long-range inhibition
or
long-range activation/short-range inhibition.
Cystic echinococcosis is a zoonotic disease caused by the parasite Echinococcus granulosus sensu lato (s.l.), which is worldwide distributed and causes long-lasting infections in animals and humans. ...The existing treatment is limited to the use of benzimidazoles, mainly albendazole (ABZ). However, it has unwanted side effects and its efficacy is about 50%. The Asteraceae family includes plants that have therapeutic applications (medicinal species) and has an important role in new drug development. The species belonging to a different genus of this family show a wide range of anti-inflammatory, antimicrobial, antioxidant, hepatoprotective, and antiparasitic activities, among others. The aim of the present study was to evaluate the in vitro efficacy of extracts of four Asteraceae species against protoscoleces of E. granulosus sensu stricto (s.s.). On the other hand, the Stevia aristata extract was assessed on the murine cyst of E. granulosus (s.s.) and the efficacy of S. aristata extract was investigated in a murine model of CE. Stevia satureiifolia, S. aristata, Grindelia pulchella, and G. chiloensis extracts at 100 μg/mL caused a decrease in protoscoleces viability; however, S. aristata extract produced the greatest in vitro protoscolicidal effect. After 20 days of treatment with the highest concentration (100 μg/mL) of S. aristata extract, protoscoleces viability decreased to 0%. The tegumental changes observed by scanning electron microscopy were consistent with the reduction in vitality. The collapse of the germinal layer was registered in 60 ± 5.8% and 83.3 ± 12.0% of cysts treated during 4 days with 50 and 100 μg/ml, respectively. The half maximal effective concentration (EC50) value of the S. aristata extract against E. granulosus (s.s.) cysts was 47.86 μg/mL (96 h). The dosage of infected animals with the 50 mg kg−1 dose of S. aristata extract resulted in a significant reduction in cyst weight in comparison with the control group. In conclusion, S. aristata extract was demonstrated to exert a marked effect, both in vitro and in the murine model.
In this paper we investigate the complex dynamics originated by a cross-diffusion-induced subharmonic destabilization of the fundamental subcritical Turing mode in a predator-prey reaction-diffusion ...system. The model we consider consists of a two-species Lotka-Volterra system with linear diffusion and a nonlinear cross-diffusion term in the predator equation. The taxis term in the search strategy of the predator is responsible for the onset of complex dynamics. In fact, our model does not exhibit any Hopf or wave instability, and on the basis of the linear analysis one should only expect stationary patterns; nevertheless, the presence of the nonlinear cross-diffusion term is able to induce a secondary instability: due to a subharmonic spatial resonance, the stationary primary branch bifurcates to an out-of-phase oscillating solution. Noticeably, the strong resonance between the harmonic and the subharmonic is able to generate the oscillating pattern albeit the subharmonic is below criticality. We show that, as the control parameter is varied, the oscillating solution (subT mode) can undergo a sequence of secondary instabilities, generating a transition toward chaotic dynamics. Finally, we investigate the emergence of subT-mode solutions on two-dimensional domains: when the fundamental mode describes a square pattern, subharmonic resonance originates oscillating square patterns. In the case of subcritical Turing hexagon solutions, the internal interactions with a subharmonic mode are able to generate the so-called "twinkling-eyes" pattern.
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