Original portrait of Carl Schurz

This black and white portrait depictc Carl Schurz as seated with one hand resting on a table in front of him. Schurz is depicted as wearing a dark suit, vest, and tie with a white shirt and eyeglasses. Shurz has a full beard. The artist\u27s name and Schurz\u27s name are written on the back of the portrait.https://scholarsjunction.msstate.edu/fvw-manuscripts-schurz/1069/thumbnail.jp

Immune Responses to Vibrio anguillarum in Yellowtail Kingfish, Seriola lalandi, Fed Selenium Supplementation

Effects of dietary selenium (Se) on immune competence of yellowtail kingfish, Seriola lalandi, were investigated. The fish were fed one of the three experimental diets including a control diet without Se supplementation and two diets supplemented with Se from Se-yeast (Selplex®) at 2 and 4mg/kg. After feeding for 6 wk, the fish were challenged by injecting Vibrio anguillarum and observed for 2wk. Dietary Se had no effect on feed intake, feed conversion ratio, and survival over the course of 6-wk feeding; however, it significantly increased weight gain and Se content in muscle. Following the bacterial infection, the immune-stimulating effects of Se were observed in antibody, lysozyme, and bactericidal responses, and there was a corresponding increase in survival and hematocrit by Se. Under infectious condition, antioxidant capacity of fish as measured in term of resistance of red blood cells to peroxidation and glutathione peroxidase activity also increased by supplementation of Se. Liver necrosis and kidneymelano-macrophages were only seen in surviving fish fed the control diet after the challenge. Furthermore, there was evidence of myopathy in fish fed the diet without Se supplementation. This study suggests that Se, supplemented at 2 or 4mg/kg, can improve growth and health of yellowtail kingfish

Activation of Host Translational Control Pathways by a Viral Developmental Switch

In response to numerous signals, latent herpesvirus genomes abruptly switch their developmental program, aborting stable host–cell colonization in favor of productive viral replication that ultimately destroys the cell. To achieve a rapid gene expression transition, newly minted capped, polyadenylated viral mRNAs must engage and reprogram the cellular translational apparatus. While transcriptional responses of viral genomes undergoing lytic reactivation have been amply documented, roles for cellular translational control pathways in enabling the latent-lytic switch have not been described. Using PEL-derived B-cells naturally infected with KSHV as a model, we define efficient reactivation conditions and demonstrate that reactivation substantially changes the protein synthesis profile. New polypeptide synthesis correlates with 4E-BP1 translational repressor inactivation, nuclear PABP accumulation, eIF4F assembly, and phosphorylation of the cap-binding protein eIF4E by Mnk1. Significantly, inhibiting Mnk1 reduces accumulation of the critical viral transactivator RTA through a post-transcriptional mechanism, limiting downstream lytic protein production, and impairs reactivation efficiency. Thus, herpesvirus reactivation from latency activates the host cap-dependent translation machinery, illustrating the importance of translational regulation in implementing new developmental instructions that drastically alter cell fate

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival