Project description:Blastocladiomycota, early diverging zoosporic (flagellated) lineages of fungi, are vastly understudied. This phylum includes the genus Coelomomyces which consists of more than eighty fungal species that are obligate parasites of arthropods. Coelomomyces lack a complete asexual life cycle, instead surviving through an obligate heteroecious alternation of generations life cycle. Despite their global distribution and interesting life cycle, little is known about Coelomomyces species. To begin to address this, we analyzed transcriptomes from across host-associated life stages including infection of larva and excised mature sporangia from the mosquito, Anopheles quadrimaculatus. We identified differentially expressed genes and over-enriched GO terms both across and within life stages and used these to make hypotheses about C. lativittatus biology. Generally, we found the C. lativittatus transcriptome to be a complex and dynamic expression landscape; GO terms related to metabolism and transport processes were over-enriched during infection and terms related to dispersal were over-enriched during sporulation. The C. lativittatus transcriptomes reported here are a valuable resource and may be leveraged toward furthering understanding of the biology of these and other early diverging fungal lineages.
Project description:<h4>Background</h4>Real-time automated analysis of videos of the microvasculature is an essential step in the development of research protocols and clinical algorithms that incorporate point-of-care microvascular analysis. In response to the call for validation studies of available automated analysis software by the European Society of Intensive Care Medicine, and building on a previous validation study in sheep, we report the first human validation study of AVA 4.<h4>Methods</h4>Two retrospective perioperative datasets of human microcirculation videos (P1 and P2) and one prospective healthy volunteer dataset (V1) were used in this validation study. Video quality was assessed using the modified Microcirculation Image Quality Selection (MIQS) score. Videos were initially analyzed with (1) AVA software 3.2 by two experienced investigators using the gold standard semi-automated method, followed by an analysis with (2) AVA automated software 4.1. Microvascular variables measured were perfused vessel density (PVD), total vessel density (TVD), and proportion of perfused vessels (PPV). Bland-Altman analysis and intraclass correlation coefficients (ICC) were used to measure agreement between the two methods. Each method's ability to discriminate between microcirculatory states before and after induction of general anesthesia was assessed using paired t-tests.<h4>Results</h4>Fifty-two videos from P1, 128 videos from P2 and 26 videos from V1 met inclusion criteria for analysis. Correlational analysis and Bland-Altman analysis revealed poor agreement and no correlation between AVA 4.1 and AVA 3.2. Following the induction of general anesthesia, TVD and PVD measured using AVA 3.2 increased significantly for P1 (p < 0.05) and P2 (p < 0.05). However, these changes could not be replicated with the data generated by AVA 4.1.<h4>Conclusions</h4>AVA 4.1 is not a suitable tool for research or clinical purposes at this time. Future validation studies of automated microvascular flow analysis software should aim to measure the new software's agreement with the gold standard, its ability to discriminate between clinical states and the quality thresholds at which its performance becomes unacceptable.
Project description:To inhibitors for ADAR1 and a strong rationale for the development of ADAR1 p150 inhibitors for cancer immunotherapy Here, we describe AVA-ADR-001, a potential first-in-class small molecule inhibitor of ADAR1 p150 targeting the Z alpha domain. AVA-ADR-001 binds specifically to the Z alpha domain of ADAR1 p150 as confirmed by fluorescence spectroscopy and showed significant interferon induction in THP1 macrophages, which have high ADAR1 p150 expression compared with monocytes. Proteomics and transcriptomics analysis revealed significant upregulation of interferon signaling upon treatment with AVA-ADR -001. Interestingly, activation of interferon signaling resulted in AVA-ADR-001 induced cell killing in ADAR1-independent cell lines. In addition, treatment with AVA-ADR -001 resulted in significant activation of PKR, which may explain the decreased cell proliferation. Finally, AVA-ADR-001 showed superior anti-tumor efficacy compared to anti-PD1 in an in vivo tumor efficacy study and has a moderately synergistic effect when combined. Overall, this study reveals that ADAR1 p150 inhibition by AVA-ADR-001 exerts a multipronged impact on anti-tumor efficacy mediated by immune cells, accumulation of interferons and activation of PKR, resulting in protein translation inhibition and cell proliferation arrest.
Project description:Global Health systems encounter increasing challenges, spread of health needs and economic constraints. Approximately, nurses are the major part of human resources working in health systems in all countries. Job dissatisfaction is one of the effective factors in nursing career exit. This study has been accomplished with purpose of determining nurses' job satisfaction in Ava Salamat Entrepreneurs Institute. This cross-sectional and descriptive research was performed in 2017. A random group of 533 nurses contributed in the study. A questionnaire was used for data collection, which included personal and career attributes, and level of job satisfaction as inputs. Data was collected over a period of three months. The Statistical Package for the Social Sciences (SPSS v22) software and descriptive statistical tests were utilized for the analysis. According to results, nurses job security was increased impressively, more than before they were employed in Ava Salamat Entrepreneurs Institute (about 62%), and they feel satisfied about their position more than before (77.1%) and have a desire to continue working for Ava Salamat Entrepreneurs Institute (75.4%). The results show that 62.9% of nurses were pleased for their prompt payment, and about 67% were dissatisfied with the proportion of their tasks and career hardship. Among those, 55.6% of nurses were satisfied by the professional support received from their managers and 51.4% of the nurses were satisfied with their image in the social profession.
Project description:In order to identify the combination of antibody-mediated mechanisms of neutralization that result from vaccination with anthrax vaccine adsorbed (AVA), we isolated antibody secreting cells from a single donor seven days after booster vaccination with AVA and generated nine fully human monoclonal antibodies (hmAb) with high specificity for protective antigen (PA). Two of the antibodies were able to neutralize lethal toxin in vitro at low concentrations (IC(50): p6C01, 0.12 ?g/ml and p6F01, 0.45 ?g/ml). Passive transfer of either of these hmAbs to A/J mice prior to challenge with lethal toxin conferred 80-90% protection. We demonstrate that hmAb p6C01 is neutralizing by preventing furin cleavage of PA in a dose-dependent manner, but the mechanism of p6F01 is unclear. Three additional antibodies were found to bind to domain 3 of PA and prevent oligomerization, although they did not confer significant protection in vivo and showed a significant prozone-like effect in vitro. These fully human antibodies provide insight into the neutralizing response to AVA for future subunit vaccine and passive immunotherapeutic cocktail design.