Suppression of Type I Interferon Signaling by Flavivirus NS5.

Type I interferon (IFN-I) is the first line of mammalian host defense against viral infection. To counteract this, the flaviviruses, like other viruses, have encoded a variety of antagonists, and use a multi-layered molecular defense strategy to establish their infections. Among the most potent antagonists is non-structural protein 5 (NS5), which has been shown for all disease-causing flaviviruses to target different steps and players of the type I IFN signaling pathway. Here, we summarize the type I IFN antagonist mechanisms used by flaviviruses with a focus on the role of NS5 in regulating one key regulator of type I IFN, signal transducer and activator of transcription 2 (STAT2)

Structure and function of Zika virus NS5 protein: perspectives for drug design.

Zika virus (ZIKV) belongs to the positive-sense single-stranded RNA-containing Flaviviridae family. Its recent outbreak and association with human diseases (e.g. neurological disorders) have raised global health concerns, and an urgency to develop a therapeutic strategy against ZIKV infection. However, there is no currently approved antiviral against ZIKV. Here we present a comprehensive overview on recent progress in structure-function investigation of ZIKV NS5 protein, the largest non-structural protein of ZIKV, which is responsible for replication of the viral genome, RNA capping and suppression of host interferon responses. Structural comparison of the N-terminal methyltransferase domain and C-terminal RNA-dependent RNA polymerase domain of ZIKV NS5 with their counterparts from related viruses provides mechanistic insights into ZIKV NS5-mediated RNA replication, and identifies residues critical for its enzymatic activities. Finally, a collection of recently identified small molecule inhibitors against ZIKV NS5 or its closely related flavivirus homologues are also discussed

Vertical Stratification of Sediment Microbial Communities Along Geochemical Gradients of a Subterranean Estuary Located at the Gloucester Beach of Virginia, United States

Subterranean estuaries (STEs) have been recognized as important ecosystems for the exchange of materials between the land and sea, but the microbial players of biogeochemical processes have not been well examined. In this study, we investigated the bacterial and archaeal communities within 10 cm depth intervals of a permeable sediment core (100 cm in length) collected from a STE located at Gloucester Point (GP-STE), VA, United States. High throughput sequencing of 16S rRNA genes and subsequent bioinformatics analyses were conducted to examine the composition, diversity, and potential functions of the sediment communities. The community composition varied significantly from the surface to a depth of 100 cm with up to 13,000 operational taxonomic units (OTUs) based on 97% sequence identities. More than 95% of the sequences consisted of bacterial OTUs, while the relative abundances of archaea, dominated by Crenarchaea, gradually increased with sediment core depth. Along the redox gradients of GP-STE, differential distribution of ammonia-and methane-oxidizing, denitrifying, and sulfate reducing bacteria was observed as well as methanogenic archaea based on predicted microbial functions. The aerobic-anaerobic transition zone (AATZ) had the highest diversity and abundance of microorganisms, matching with the predicted functional diversity. This indicates the AATZ as a hotspot of biogeochemical processes of STEs. The physical and geochemical gradients in different depths have attributed to vertical stratification of microbial community composition and function in the GP-STE

Systematic overview of economic evaluations of health-related rehabilitation

Background: Health related rehabilitation is instrumental in improving functioning and promoting participation by people with disabilities. To make clinical and policy decisions about health-related rehabilitation, resource allocation and cost issues need to be considered. Objectives: To conduct an overview of systematic reviews (SRs) on economic evaluations of health-related rehabilitation. Methods: We searched multiple databases to identify relevant SRs of economic evaluations of health-related rehabilitation. Review quality was assessed by AMSTAR checklist. Results: We included 64 SRs, most of which included economic evaluations alongside randomised controlled trials (RCTs). The review quality was low to moderate (AMSTAR score 5-8) in 35, and high (score 9-11) in 29 of the included SRs. The included SRs addressed various health conditions, including spinal or other pain conditions (n=14), age-related problems (11), stroke (7), musculoskeletal disorders (6), heart diseases (4), pulmonary (3), mental health problems (3), and injury (3). Physiotherapy was the most commonly evaluated rehabilitation intervention in the included SRs (n=24). Other commonly evaluated interventions included multidisciplinary programmes (14); behavioural, educational or psychological interventions (11); home-based interventions (11); complementary therapy (6); self-management (6); and occupational therapy (4). Conclusions: Although the available evidence is often described as limited, inconsistent or inconclusive, some rehabilitation interventions were cost-effective or showed cost-saving in a variety of disability conditions. Available evidence comes predominantly from high income countries, therefore economic evaluations of health-related rehabilitation are urgently required in less resourced settings

Occupational Responses of Older Adults Following Partner Loss

Spousal loss has been frequently identified as a life stressor that can greatly impede one’s ability to age at home. The purpose of this study is to identify the occupational changes that commonly result after this event and their impacts on one’s ability to age in place. This study utilized a qualitative phenomenological research design. Eight participants were recruited from an educational program for older adults and were interviewed using a semi-structured interview format. Researchers transcribed and coded all interviews to determine emergent themes. Two major categories of themes were found: occupational and intrinsic responses. The areas of occupation that were most commonly identified include: social participation, caregiving, activities of daily living, financial and household management, meal preparation, and leisure. Intrinsic responses were identified as autonomy, intrapersonal transition, and filling in time. Occupational and intrinsic responses occur transactionally and influence each other. Older adults may need to effectively address changes to both of these categories to facilitate successful aging in place after partner loss.https://scholar.dominican.edu/ug-student-posters/1085/thumbnail.jp

Predominant Coaching Leadership Behaviors of High School Head Basketball Coaches: A Pilot Study

Coaching leadership in sport was important because the coach-athlete relationship was considered as a crucial factor in the sport setting. Though leadership theories have been developed for a few decades, research topics related to leadership behaviors in high school settings are understudied. The purpose of the study was to examine the coaching leadership behaviors of high school head basketball coaches in Hong Kong utilizing the Leadership Scale for Sports. One hundred and twelve basketball coaches were invited to participate in the study: 56 coaches from the winning teams and another 56 coaches from the losing teams. Mixed-design 2 × 5 ANOVA indicated there was significant (p \u3c .001) main effect for the coaching behaviors. Both the top-ranking and low-ranking head basketball coaches exhibited significantly (p \u3c .001) higher level of Teaching and Instruction as well as Positive Feedback than Social Support, Democratic Behavior, and Autocratic Behavior. The mean scores as determined by the five dimensions of the LSS were in the following descending order: Positive Feedback, Training and Instruction, Social Support, Democratic Behavior, and Autocratic Behavior. The importance and application of these five coaching behaviors were discussed in detail

Comparative study of numerical modelling techniques to estimate tidal turbine blade loads

This paper presents a method to obtain the pressure distribution across the surface of a tidal turbine blade, but without the extensive computational time that is required by 3D CFD modelling. The approach uses a combination of blade element momentum theory (BEMT) and 2D CFD modelling, where the inflow velocity vector for each blade element computed from the BEMT model is input to a 2D CFD model of each of the blade sections. To assess the validity of this approach, a comparison is made with both a BEMT and a 3D CFD model for three different blade profiles at full scale (NACA 63-8xx, NREL S814 and Wortmann FX 63-137). A comparison is also made of the NREL blade at smaller scale to investigate any Reynolds number effects on the model performance. The agreement is shown to be very reasonable between the three methods, although the forces are consistently slightly over-predicted by the BEMT method compared to the 2D-CFD-BEMT model, and the 2D-CFD-BEMT model over-predicts the pressure along the leading edge compared to the 3D CFD results. The proposed method is shown to be particularly useful when conducting initial blade structural analysis under dynamic loading

Characterization of Kaposi's sarcoma-associated herpesvirus (KSHV) K1 promoter activation by Rta

The K1 gene of Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a 46-kDa transmembrane glycoprotein that possesses transforming properties, initiates signaling pathways in B cells, and prevents apoptosis. Here, we demonstrate a mechanism for activation of the K1 promoter by the Rta transactivator. Electrophoretic mobility shift assay (EMSA) analysis of the K1 promoter demonstrated that purified Rta protein bound to the K1 promoter at three locations, independent of other DNA-binding factors. Transcriptional assays revealed that only two of these Rta DNA-binding sites are functionally significant, and that they could impart Rta responsiveness to a heterologous E4 TATA box promoter. In addition, TATA-binding protein (TBP) bound to a TATA box element located 25 bp upstream of the K1 transcription start site and was also shown to associate with Rta by coimmunoprecipitation analysis. Rta transactivation may therefore be mediated in part through recruitment of TBP to target promoters

Netrin-1-like Peptides Are Secreted by Tetrahymena thermophila

Netrin-1 is a peptide signaling molecule that has many roles in vertebrates. In the ciliated protozoan, Tetrahymena thermophila, netrin-1 acts as a chemorepellent, causing cells to exhibit a characteristic avoidance behavior. We have previously shown that netrin-1 avoidance by T. thermophila is inhibited by genistein, which is a broad spectrum tyrosine kinase inhibitor. One question we wished to answer in our current study was, “Is genistein specifically acting upon tyrosine kinases in order to inhibit netrin avoidance in Tetrahymena?” In order to answer this question, we used the phytoestrogen, diadzein, as a negative control for genistein inhibition. Diadzein had no effect on avoidance, suggesting that genistein inhibition is specific. In order to gain more information about the nature of the kinases involved in netrin-1 signaling, we tested several other kinase inhibitors, including a src inhibitor, a focal adhesion kinase inhibitor, and a Rho kinase inhibitor. Each of these kinases has been implicated in netrin-1 signaling in some vertebrate cell types. However, none of these inhibitors affected Tetrahymena avoidance to netrin-1. Finally, we wished to answer the question, “Is netrin-1 actually serving an autocrine signaling role in Tetrahymena, or is the peptide merely serving as an agonist for another receptor?” In order to answer this question, we prepared a whole cell extract of Tetrahymena using 0.1% SDS. We also washed Tetrahymena in our behavioral buffer and allowed them to sit in that buffer for 24 hours. The Tetrahymena were centrifuged out of the buffer, and the supernatant, containing the proteins which the Tetrahymena had secreted, was kept for ELISA assay. An ELISA, using a polyclonal anti netrin-1 antibody, was run on the whole cell extract and the secreted proteins against a netrin-1 standard curve. Both the secreted proteins and the whole cell extract tested positive for netrin-1 in the ELISA. Further experimentation will allow us to determine the nature of these netrin-like peptides