Engagement of TRAIL triggers degranulation and IFNγ production in human natural killer cells.

NK cells utilize a large array of receptors to screen their surroundings for aberrant or virus-infected cells. Given the vast diversity of receptors expressed on NK cells we seek to identify receptors involved in the recognition of HIV-1-infected cells. By combining an unbiased large-scale screening approach with a functional assay, we identify TRAIL to be associated with NK cell degranulation against HIV-1-infected target cells. Further investigating the underlying mechanisms, we demonstrate that TRAIL is able to elicit multiple effector functions in human NK cells independent of receptor-mediated induction of apoptosis. Direct engagement of TRAIL not only results in degranulation but also IFNγ production. Moreover, TRAIL-mediated NK cell activation is not limited to its cognate death receptors but also decoy receptor I, adding a new perspective to the perceived regulatory role of decoy receptors in TRAIL-mediated cytotoxicity. Based on these findings, we propose that TRAIL not only contributes to the anti-HIV-1 activity of NK cells but also possesses a multifunctional role beyond receptor-mediated induction of apoptosis, acting as a regulator for the induction of different effector functions.

Quality of breeding value predictions from longitudinal analyses, with application to residual feed intake in pigs.

BACKGROUND: An important goal in animal breeding is to improve longitudinal traits. The objective of this study was to explore for longitudinal residual feed intake (RFI) data, which estimated breeding value (EBV), or combination of EBV, to use in a breeding program. Linear combinations of EBV (summarized breeding values, SBV) or phenotypes (summarized phenotypes) derived from the eigenvectors of the genetic covariance matrix over time were considered, and the linear regression method (LR method) was used to facilitate the evaluation of their prediction accuracy. RESULTS: Weekly feed intake, average daily gain, metabolic body weight, and backfat thickness measured on 2435 growing French Large White pigs over a 10-week period were analysed using a random regression model. In this population, the 544 dams of the phenotyped animals were genotyped. These dams did not have own phenotypes. The quality of the predictions of SBV and breeding values from summarized phenotypes of these females was evaluated. On average, predictions of SBV at the time of selection were unbiased, slightly over-dispersed and less accurate than those obtained with additional phenotypic information. The use of genomic information did not improve the quality of predictions. The use of summarized instead of longitudinal phenotypes resulted in predictions of breeding values of similar quality. CONCLUSIONS: For practical selection on longitudinal data, the results obtained with this specific design suggest that the use of summarized phenotypes could facilitate routine genetic evaluation of longitudinal traits.

New residual feed intake criterion for longitudinal data.

BACKGROUND: Residual feed intake (RFI) is one measure of feed efficiency, which is usually obtained by multiple regression of feed intake (FI) on measures of production, body weight gain and tissue composition. If phenotypic regression is used, the resulting RFI is generally not genetically independent of production traits, whereas if RFI is computed using genetic regression coefficients, RFI and production traits are independent at the genetic level. The corresponding regression coefficients can be easily derived from the result of a multiple trait model that includes FI and production traits. However, this approach is difficult to apply in the case of multiple repeated measurements of FI and production traits. To overcome this difficulty, we used a structured antedependence approach to account for the longitudinality of the data with a phenotypic regression model or with different genetic and environmental regression coefficients [multi- structured antedependence model (SAD) regression model]. RESULTS: After demonstrating the properties of RFI obtained by the multi-SAD regression model, we applied the two models to FI and production traits that were recorded for 2435 French Large White pigs over a 10-week period. Heritability estimates were moderate with both models. With the multi-SAD regression model, heritability estimates were quite stable over time, ranging from 0.14 ± 0.04 to 0.16 ± 0.05, while heritability estimates showed a U-shaped profile with the phenotypic regression model (ranging from 0.19 ± 0.06 to 0.28 ± 0.06). Estimates of genetic correlations between RFI at different time points followed the same pattern for the two models but higher estimates were obtained with the phenotypic regression model. Estimates of breeding values that can be used for selection were obtained by eigen-decomposition of the genetic covariance matrix. Correlations between these estimated breeding values obtained with the two models ranged from 0.66 to 0.83. CONCLUSIONS: The multi-SAD model is preferred for the genetic analysis of longitudinal RFI because, compared to the phenotypic regression model, it provides RFI that are genetically independent of production traits at all time points. Furthermore, it can be applied even when production records are missing at certain time points.

Knowledge, Attitudes, Practices, and Related Factors Towards COVID-19 Prevention Among Patients at University Medical Center Ho Chi Minh City, Vietnam.

AIM: This study measured the level of knowledge, attitudes and practices towards COVID-19 prevention and examined associated factors among patients at a national tertiary general hospital in Vietnam. METHODS: Adult patients admitted to University Medical Center during research period were recruited in a cross-sectional study, which employed a convenience sampling method with a 4-component questionnaire in order to examine the patients' consciousness towards COVID-19 spreading prevention based on four aspects: demographic characteristics (10 items), knowledge (14 items), attitudes (6 items), and practices (7 items). RESULTS: The study involved 2769 respondents (18-90 years) with the mean age of 38.05±13.91 years. About two thirds of the respondents obtained diploma degree or higher (63.4%) and shared their living space with others (64.4%). The majority of patients settled in urban area (74.9%). All participants stayed informed about COVID-19, with the most commonly used channels like television (75.2%), the Internet (72.2%) and phone (69.8%). The vast majority showed sufficient knowledge (93.7%) and positive attitudes (76.3%). Just over half of participants remained good practiced of COVID-19 prevention (57.7%). On average, the factors of younger age, higher educational level, frequency and department of admission, and the number of COVID-19 informative channels were significantly associated with sufficient knowledge, positive attitudes, and good practices regarding preventive action against COVID-19 spreading. The optimistic attitude and having more undergoing chronic diseases were associated with the likelihood of well-practiced COVID-19 preventive measures (OR 3.63, 95% CI 1.54-8.55, p=0.003 and OR 0.86, 95% CI 0.78-0.98, p=0.02, respectively). CONCLUSION: The results of this study demonstrated that the likelihood of good preventive practices in the fight against COVID-19 pandemic was influenced by attitudes and several sociodemographic factors. More drastic interventions for the prevention of COVID-19 should be widely furnished and equipped in hospitals, through various routes to maximize the efficiency and adherence to prevention practices.

Distinct Signatures in the Receptor Repertoire Discriminate CD56bright and CD56dim Natural Killer Cells.

NK cells are phenotypically and functionally diverse lymphocytes due to variegated expression of a large array of receptors. NK-cell activity is tightly regulated through integration of receptor-derived inhibitory and activating signals. Thus, the receptor profile of each NK cell ultimately determines its ability to sense aberrant cells and subsequently mediate anti-viral or anti-tumor responses. However, an in-depth understanding of how different receptor repertoires enable distinct immune functions of NK cells is lacking. Therefore, we investigated the phenotypic diversity of primary human NK cells by performing extensive phenotypic characterization of 338 surface molecules using flow cytometry (n = 18). Our results showed that NK cells express at least 146 receptors on their surface. Of those, 136 (>90%) exhibited considerable inter-donor variability. Moreover, comparative analysis of CD56bright and CD56dim NK cells identified 70 molecules with differential expression between the two major NK-cell subsets and allowed discrimination of these subsets via unsupervised hierarchical clustering. These receptors were associated with a broad range of NK-cell functions and multiple molecules were not previously associated with predominant expression on either subset (e.g. CD82 and CD147). Altogether, our study contributes to an improved understanding of the phenotypic diversity of NK cells and its potential functional implications on a cellular and population level. While the identified distinct signatures in the receptor repertoires provide a molecular basis for the differential immune functions exerted by CD56bright and CD56dim NK cells, the observed inter-individual differences in the receptor repertoire of NK cells may contribute to a diverging ability to control certain diseases.

Ex-Vivo percutaneous absorption of enrofloxacin: Comparison of LMOG organogel vs. pentravan cream.

The objective of this study was to investigate the percutaneous absorption of enrofloxacin from two base formulations, Pentravan cream and LMOG organogel. Ex-vivo experiments were carried out on pig ear skin. The percutaneous permeation through pig skin of two formulations containing 5 wt% of enrofloxacin was measured and compared using Franz diffusion cells. At appropriate intervals up to 120 h, diffusion samples were taken and analyzed using HPLC assays. Permeation profiles were established and the parameters Tlag and flux values were calculated. In this ex-vivo study, the flux values were 0.35 µgcm(-2)h(-1) for Pentravan and 1.22 µgcm(-2)h(-1) for LMOG organogel, corresponding respectively to 7.9 % and 29.3 % of enrofloxacin absorbed after 120 h by these formulations. The lag time (T lag) of Pentravan and organogel were 6.32 and 0.015 h respectively. The absorption time to reach the antibiotic concentration of enrofloxacin (2 µgmL(-1)) in the receptor was 60 h with Pentravan and 30 h with the organogel, suggesting more effective treatment by the latter. Enrofloxacin contained in organogel could be absorbed through pig ear skin 3.7 times greater than that in Pentravan (commercial formulation). This study demonstrates the perspective of organogel formulations as potential drug delivery systems.

Dose mapping using MCNP code and experiment for SVST-Co-60/B irradiator in Vietnam.

By using MCNP code and ethanol-chlorobenzene (ECB) dosimeters the simulations and measurements of absorbed dose distribution in a tote-box of the Cobalt-60 irradiator, SVST-Co60/B at VINAGAMMA have been done. Based on the results Dose Uniformity Ratios (DUR), positions and values of minimum and maximum dose extremes in a tote-box, and efficiency of the irradiator for the different dummy densities have been gained. There is a good agreement between simulation and experimental results in comparison and they have valuable meanings for operation of the irradiator.