54 research outputs found

    TRAIL Death Receptor-4, Decoy Receptor-1 and Decoy Receptor-2 Expression on CD8+ T Cells Correlate with the Disease Severity in Patients with Rheumatoid Arthritis

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    BACKGROUND: Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disorder. Although the pathogenesis of disease is unclear, it is well known that T cells play a major role in both development and perpetuation of RA through activating macrophages and B cells. Since the lack of TNF-Related Apoptosis Inducing Ligand (TRAIL) expression resulted in defective thymocyte apoptosis leading to an autoimmune disease, we explored evidence for alterations in TRAIL/TRAIL receptor expression on peripheral T lymphocytes in the molecular mechanism of RA development. METHODS: The expression of TRAIL/TRAIL receptors on T cells in 20 RA patients and 12 control individuals were analyzed using flow cytometry. The correlation of TRAIL and its receptor expression profile was compared with clinical RA parameters (RA activity scored as per DAS28) using Spearman Rho Analysis. RESULTS: While no change was detected in the ratio of CD4+ to CD8+ T cells between controls and RA patient groups, upregulation of TRAIL and its receptors (both death and decoy) was detected on both CD4+ and CD8+ T cells in RA patients compared to control individuals. Death Receptor-4 (DR4) and the decoy receptors DcR1 and DcR2 on CD8+ T cells, but not on CD4+ T cells, were positively correlated with patients' DAS scores. CONCLUSIONS: Our data suggest that TRAIL/TRAIL receptor expression profiles on T cells might be important in revelation of RA pathogenesis

    Robot education peers in a situated primary school study: personalisation promotes child learning

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    The benefit of social robots to support child learning in an educational context over an extended period of time is evaluated. Specifically, the effect of personalisation and adaptation of robot social behaviour is assessed. Two autonomous robots were embedded within two matched classrooms of a primary school for a continuous two week period without experimenter supervision to act as learning companions for the children for familiar and novel subjects. Results suggest that while children in both personalised and non-personalised conditions learned, there was increased child learning of a novel subject exhibited when interacting with a robot that personalised its behaviours, with indications that this benefit extended to other class-based performance. Additional evidence was obtained suggesting that there is increased acceptance of the personalised robot peer over a non-personalised version. These results provide the first evidence in support of peer-robot behavioural personalisation having a positive influence on learning when embedded in a learning environment for an extended period of time

    Adhesion Failures Determine the Pattern of Choroidal Neovascularization in the Eye: A Computer Simulation Study

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    Choroidal neovascularization (CNV) of the macular area of the retina is the major cause of severe vision loss in adults. In CNV, after choriocapillaries initially penetrate Bruch's membrane (BrM), invading vessels may regress or expand (CNV initiation). Next, during Early and Late CNV, the expanding vasculature usually spreads in one of three distinct patterns: in a layer between BrM and the retinal pigment epithelium (sub-RPE or Type 1 CNV), in a layer between the RPE and the photoreceptors (sub-retinal or Type 2 CNV) or in both loci simultaneously (combined pattern or Type 3 CNV). While most studies hypothesize that CNV primarily results from growth-factor effects or holes in BrM, our three-dimensional simulations of multi-cell model of the normal and pathological maculae recapitulate the three growth patterns, under the hypothesis that CNV results from combinations of impairment of: 1) RPE-RPE epithelial junctional adhesion, 2) Adhesion of the RPE basement membrane complex to BrM (RPE-BrM adhesion), and 3) Adhesion of the RPE to the photoreceptor outer segments (RPE-POS adhesion). Our key findings are that when an endothelial tip cell penetrates BrM: 1) RPE with normal epithelial junctions, basal attachment to BrM and apical attachment to POS resists CNV. 2) Small holes in BrM do not, by themselves, initiate CNV. 3) RPE with normal epithelial junctions and normal apical RPE-POS adhesion, but weak adhesion to BrM (e.g. due to lipid accumulation in BrM) results in Early sub-RPE CNV. 4) Normal adhesion of RBaM to BrM, but reduced apical RPE-POS or epithelial RPE-RPE adhesion (e.g. due to inflammation) results in Early sub-retinal CNV. 5) Simultaneous reduction in RPE-RPE epithelial binding and RPE-BrM adhesion results in either sub-RPE or sub-retinal CNV which often progresses to combined pattern CNV. These findings suggest that defects in adhesion dominate CNV initiation and progression

    Analysis of apoptosis methods recently used in Cancer Research and Cell Death & Disease publications

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    Using machine learning to identify important predictors of COVID-19 infection prevention behaviors during the early phase of the pandemic

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    Before vaccines for coronavirus disease 2019 (COVID-19) became available, a set of infection-prevention behaviors constituted the primary means to mitigate the virus spread. Our study aimed to identify important predictors of this set of behaviors. Whereas social and health psychological theories suggest a limited set of predictors, machine-learning analyses can identify correlates from a larger pool of candidate predictors. We used random forests to rank 115 candidate correlates of infection-prevention behavior in 56,072 participants across 28 countries, administered in March to May 2020. The machine-learning model predicted 52% of the variance in infection-prevention behavior in a separate test sample—exceeding the performance of psychological models of health behavior. Results indicated the two most important predictors related to individual-level injunctive norms. Illustrating how data-driven methods can complement theory, some of the most important predictors were not derived from theories of health behavior—and some theoretically derived predictors were relatively unimportant

    OXIDATION-KINETICS OF A TURKISH OIL-SHALE

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    Oxidation kinetics of a Turkish oil shale (Bolu-Himmetoglu), when subjected to an air flow of 1.5 L/min at different pressures, was studied. CO, CO2 and O2 gas concentrations were measured as a function of controlled increasing temperature. The reaction rate equation obtained at the end of the kinetics study showed that oxidation of oil shale is dependent upon oxygen partial pressure and organic matter content, and that the relation between reaction rate constant and temperature fits an Arrhenius type of equation. The oxidation reaction was determined to occur in three stages; low temperature, transition and high temperature zones. The rate controlling mechanism was observed to be chemical kinetics in the first region, while diffusion was rate controlling in the last stage of the reaction

    Knockdown of Type 3 Iodothyronine Deiodinase Severely Perturbs Both Embryonic and Early Larval Development in Zebrafish

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    Exposure to appropriate levels of thyroid hormones (THs) at the right time is of key importance for normal development in all vertebrates. Type 3 iodothyronine deiodinase (D3) is the prime TH-inactivating enzyme, and its expression is highest in the early stages of vertebrate development, implying that it may be necessary to shield developing tissues from overexposure to THs. We used antisense morpholino knockdown to examine the role of D3 during early development in zebrafish. Zebrafish possess 2 D3 genes, dio3a and dio3b. Here, we show that both genes are expressed during development and both contribute to in vivo D3 activity. However, dio3b mRNA levels inembryosare higher, and the effects of dio3b knockdown on D3 activity and on the resulting phenotype are more severe. D3 knockdown induced an overall delay in development, as determined by measurements of otic vesicle length, eye and ear size, and body length. The time of hatching was also severely delayed in D3-knockdown embryos. Importantly, we also observed a severe disturbance of several aspects of development. Swim bladder development and inflation was aberrant as was the development of liver and intestine. Furthermore, D3-knockdown larvae spent significantly less time moving, and both embryos and larvae exhibited perturbed escape responses, suggesting that D3 knockdown affects muscle development and/or functioning. These data indicate that D3 is essential for normal zebrafish embryonic and early larval development and show the value of morpholino knockdown in this model to further elucidate the specific role of D3 in some aspects of vertebrate development
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