ABSTRACT
BackgroundEarly in the pandemic, transmission risk from asymptomatic infection was unclear making it imperative to monitor infection in workplace settings. Further, data on SARS-CoV-2 seroprevalence within university populations has been limited. MethodsWe performed a longitudinal study of University research employees on campus July-December 2020. We conducted questionnaires on COVID-19 risk factors, RT-PCR testing, and SARS-CoV-2 serology using an in-house spike RBD assay, laboratory-based Spike NTD assay, and standard nucleocapsid platform assay. We estimated prevalence and cumulative incidence of seroconversion with 95% confidence intervals using the inverse of the Kaplan-Meier estimator. Results910 individuals were included in this analysis. At baseline, 6.2% (95% CI 4.29-8.19) were seropositive using the spike RBD assay; four (0.4%) were seropositive using the nucleocapsid assay, and 44 (4.8%) using the Spike NTD assay. Cumulative incidence was 3.61% (95% CI: 2.04-5.16). Six asymptomatic individuals had positive RT-PCR results. ConclusionsPrevalence and incidence of SARS-CoV-2 infections was low; however differences in target antigens of serological tests provided different estimates. Future research on appropriate methods of serological testing in unvaccinated and vaccinated populations is needed. Frequent RT-PCR testing of asymptomatic individuals is required to detect acute infections, and repeated serosurveys are beneficial for monitoring subclinical infection.
ABSTRACT
Histone deacetylases (HDACs), originally described as histone modifiers, have more recently been demonstrated to target a variety of other proteins unrelated to the chromatin environment. In this context, our present work demonstrates that the pharmacological or genetic abrogation of HDAC6 in primary melanoma samples and cell lines, down-regulates the expression of PD-L1, an important co-stimulatory molecule expressed in cancer cells, which activates the inhibitory regulatory pathway PD-1 in T-cells. Our data suggests that this novel mechanism of PD-L1 regulation is mainly mediated by the influence of HDAC6 over the recruitment and activation of STAT3. Additionally, we observed that selective HDAC6 inhibitors impairs tumor growth and reduce the in vivo expression of several inhibitory check-point molecules and other regulatory pathways involved in immunosurveillance. Most importantly, these results provide a key pre-clinical rationale and justification to further study isotype selective HDAC6 inhibitors as potential immuno-modulatory agents in cancer.
Subject(s)
B7-H1 Antigen/genetics , Gene Expression Regulation, Neoplastic , Histone Deacetylases/metabolism , Melanoma/genetics , Skin Neoplasms/genetics , Animals , Cell Line, Tumor , Cytokines/metabolism , Gene Knockdown Techniques , Histone Deacetylase 6 , Histone Deacetylases/genetics , Humans , Melanoma/metabolism , Melanoma/pathology , Mice, Inbred C57BL , Promoter Regions, Genetic , STAT3 Transcription Factor/metabolism , Signal Transduction , Skin/metabolism , Skin/pathology , Skin Neoplasms/metabolism , Skin Neoplasms/pathologyABSTRACT
Orientational order parameters determined from (1)H NMR spectroscopy of solutes in liquid crystals that form both nematic and smectic A phases are used to determine the solute smectic A order parameters and the smectic-nematic coupling term. For the analysis, it is necessary to know the nematic part of the potential in the smectic A phase: various ways of extrapolating parameters from the nematic phase to the smectic phase are explored.
