Development of a Reagent for Evaluation of Incipient Immune Response to the Live Plague Vaccine

Objective of the study is to develop a reagent for the detection of lymphocytes with Yersinia pestis F1 antigen receptors. Materials and methods. Utilized have been: live plague vaccine based on the strain of Yersinia pestis EV NIIEG, formalin killed suspensions of microorganisms - Y. pestis , 3123, Y. enterocolitica O9 H-383 serovar, Y. pseudotuberculosis O1 2841 serovar; acetaldehyde-immobilized capsular antigen of Y. pestis F1 (obtained applying Baker methodology), lipopolysaccharide of Y. pestis K1, and bovine erythrocytes. Bovine erythrocyte F1 sensibilization has been performed using rivanol. Lymphocytes from blood have been isolated in density gradient ficoll-verografin 1.077. Lymphocytes with Yersinia pestis F1 antigen receptors have been detected by means of reagent adhesion onto the isolated lymphocytes. F1-free erythrocytes serve as controls. After the exposition, 7 evaluations of specificity to F1 and the lymphocytes, binding control reagent, have been carried out. Deployed have been 8 rabbits, immunized with live vaccine EV, and 2 rabbits, immunized with inactivated vaccine EV. Examined have been EV-vaccinated 5 persons. Results and conclusions. Identified is optimum sensibilizing dose of F1 antigen (250 µg/ml). Specificity of lymphocytes with receptors to F1 is demonstrated in inhibition experiments applying homologous and heterogeneous antigens. Lymphocytes with receptors to F1 (LRs) have been detected in peripheral blood of all rabbits and humans, immunized with vaccine EV. LRs have been registered since day 2 till day 35 in the rabbits, and in humans - since day 2 till day 14 after vaccination. It is shown that in case of revaccination of humans, LRs emerge and disappear earlier, than in case of primary immunization

Fabrication of Cu-W Nanocomposites by Integration of Self-Propagating High-Temperature Synthesis and Hot Explosive Consolidation Technologies

Manufacturing W-Cu composite nanopowders was performed via joint reduction of CuO and WO3 oxides with various ratios (W:Cu = 2:1, 1:1, 1:3, 1:13.5) using combined Mg–C reducer. Combustion synthesis was used to synthesize homogeneous composite powders of W-Cu and hot explosive consolidation (HEC) technique was utilized to fabricate dense compacts from ultrafine structured W-Cu powders. Compact samples obtained from nanometer sized SHS powders demonstrated weak relation between the susceptibility and the applied magnetic field in comparison with the W and Cu containing micrometer grain size of metals. The density, microstructural uniformity and mechanical properties of SHS&HEC prepared samples were also evaluated. Internal friction (Q-1) and Young modulus (E) of fabricated composites studied for all samples indicated that the temperature 1000 °С is optimal for full annealing of microscopic defects of structure and internal stresses. Improved characteristics for Young modulus and internal friction were obtained for the W:Cu = 1:13.5 composite. According to microhardness measurement results, W-Cu nanopowders obtained by SHS method and compacted by HEC technology were characterized by enhanced (up to 85%) microhardness

Ewing Sarcoma Protein Ewsr1 Maintains Mitotic Integrity and Proneural Cell Survival in the Zebrafish Embryo

BACKGROUND:The Ewing sarcoma breakpoint region 1 gene (EWSR1), also known as EWS, is fused to a number of different partner genes as a result of chromosomal translocation in diverse sarcomas. Despite the involvement of EWSR1 in these diverse sarcomas, the in vivo function of wild type EWSR1 remains unclear. PRINCIPAL FINDINGS:We identified two zebrafish EWSR1 orthologues, ewsr1a and ewsr1b, and demonstrate that both genes are expressed maternally, and are expressed ubiquitously throughout zebrafish embryonic development. Morpholino induced knockdown of both zebrafish ewsr1 genes led to mitotic defects with multipolar or otherwise abnormal mitotic spindles starting from the bud stage (10 hour post-fertilization (hpf)). The abnormalities in mitotic spindles were followed by p53-mediated apoptosis in the developing central nervous system (CNS) leading to a reduction in the number of proneural cells, disorganization of neuronal networks, and embryonic lethality by 5 days post-fertilization. siRNA silencing of EWSR1 in Hela cells resulted in mitotic defects accompanied by apoptotic cell death, indicating that the role of EWSR1 is conserved between zebrafish and human. CONCLUSIONS:Ewsr1 maintains mitotic integrity and proneural cell survival in early zebrafish development

The impact of formative testing on study behaviour and study performance of (bio)medical students: a smartphone application intervention study.

BACKGROUND: Formative testing can increase knowledge retention but students often underuse available opportunities. Applying modern technology to make the formative tests more attractive for students could enhance the implementation of formative testing as a learning tool. This study aimed to determine whether formative testing using an internet-based application ("app") can positively affect study behaviour as well as study performance of (bio)medical students. METHODS: A formative testing app "Physiomics, to the next level" was introduced during a 4-week course to a large cohort (n = 461) of Dutch first year (bio)medical students of the Radboud University. The app invited students to complete 7 formative tests throughout the course. Each module was available for 3-4 days to stimulate the students to distribute their study activities throughout the 4-week course. RESULTS: 72% of the students used the app during the course. Study time significantly increased in intensive users (p < 0.001), while no changes were observed in moderate (p = 0.07) and non-users (p = 0.25). App-users obtained significantly higher grades during the final exam of the course (p < 0.05). Non-users more frequently failed their final exam (34%, OR 3.6, 95% CI: 2.0-6.4) compared to moderate users (19%) and intensive users (12%). Students with an average grade <6.5 during previous courses benefitted most from the app, as intensive (5.8 ± 0.9 / 36%) and moderate users (5.8 ± 0.9 / 33%) obtained higher grades and failed their exam less frequently compared to non-users (5.2 ± 1.1 / 61%). The app was also well appreciated by students; students scored the app with a grade of 7.3 ± 1.0 out of 10 and 59% of the students indicated that they would like the app to be implemented in future courses. CONCLUSIONS: A smartphone-based application of formative testing is an effective and attractive intervention to stimulate study behaviour and improve study performance in (bio) medical students

Revelation of Immune Memory at the First Stage of Antigen-Specific Cell Response after Second Introduction of the Live Plague Vaccine

Background. The study of immune memory is necessary to evaluate the effectiveness of immunization against infection, including plague and to make a choice of vaccination scheme.Goals. The goal is to study the possible role of immune memory in the early stage of the antigen-specific response – the formation of cells with receptors for capsular (F1) and lipopolysaccharide (LPS) antigens of plague live EV vaccine.Methodology. Volunteers vaccinated with live plague vaccine EV for the first time (6 persons – group 1) and again (6 persons – group 2) were examined. In the mononuclear fraction of the blood of volunteers the cells binding antigens F1 and LPS Y. pestis (CBA) were determined.Results. In the volunteers group 2, the content of CBA at 2 days after vaccination was higher than in group 1. Between the 5th day and the end of the CBA detection, their content in group 2 decreased, and in group 1, it increased, but remained significantly less than in group 2 two days after immunization.Сonclusions. It is shown that the previous vaccination accelerates the first stage of the antigen-specific human response to second vaccination against plague. This reflects the role of immune memory in the formation of this stage of the immune response at vaccination against plague