Dengue virus-specific human T cell clones. Serotype crossreactive proliferation, interferon gamma production, and cytotoxic activity

The severe complications of dengue virus infections, hemorrhagic manifestation and shock, are much more commonly observed during secondary infections caused by a different serotype of dengue virus than that which caused the primary infections. It has been speculated, therefore, that dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are caused by serotype crossreactive immunopathological mechanisms. We analyzed clones of dengue serotype crossreactive T lymphocytes derived from the PBMC of a donor who had been infected with dengue 3 virus. These PBMC responded best to dengue 3 antigen, but also responded to dengue 1, 2, and 4 antigens, in bulk culture proliferation assays. 12 dengue antigen-specific clones were established using a limiting dilution technique. All of the clones had CD3+ CD4+ CD8 phenotypes. Eight clones responded to dengue 1, 2, 3, and 4 antigens and are crossreactive, while four other clones responded predominantly to dengue 3 antigen. These results indicate that the serotype crossreactive dengue-specific T lymphocyte proliferation observed in bulk cultures reflects the crossreactive responses detected at the clonal level. Serotype crossreactive clones produced high titers of IFN-gamma after stimulation with dengue 3 antigens, and also produced IFN-gamma to lower levels after stimulation with dengue 1, 2, and 4 antigens. The crossreactive clones lysed autologous lymphoblastoid cell line (LCL) pulsed with dengue antigens, and the crossreactivity of CTL lysis by T cell clones was consistent with the crossreactivity observed in proliferation assays. Epidemiological studies have shown that secondary infections with dengue 2 virus cause DHF/DSS at a higher rate than the other serotypes. We hypothesized that the lysis of dengue virus-infected cells by CTL may lead to DHF/DSS; therefore, the clones were examined for cytotoxic activity against dengue 2 virus-infected LCL. All but one of the serotype crossreactive clones lysed dengue 2 virus-infected autologous LCL, and they did not lyse uninfected autologous LCL. The lysis of dengue antigen-pulsed or virus-infected LCL by the crossreactive CTL clones that we have examined is restricted by HLA DP or DQ antigens. These results indicate that primary dengue virus infections induce predominantly crossreactive memory CD4+ T lymphocytes. These crossreactive T lymphocytes proliferate and produce IFN-gamma after stimulation with a virus strain of another serotype, and demonstrate crossreactive cyotoxic activity against autologous cells infected with heterologous dengue viruses.(ABSTRACT TRUNCATED AT 400 WORDS

Review and suggestions for upgrading StrandNet as a key element of the Reef 2050 Integrated Monitoring and Reporting Program: final report of the StrandNet team in the megafauna expert group

The objective of this report is to provide an overview of the present StrandNet program and suggest how it might be improved to enable the StrandNet database to function as a central component of the megafauna component of the Reef 2050 Integrated Monitoring and Reporting Program (RIMReP). The report results from a cross-sectoral, expert workshop held in Brisbane on 11 June 2018 and attended by personnel from the Great Barrier Reef Marine Park Authority, Queensland government departments of Environment and Science and Agriculture and Fisheries, James Cook University and the University of Queensland, plus subsequent input from some of the workshop attendees

High levels of interferon alpha in the sera of children with dengue virus infection

We measured the levels of interferon alpha (IFN alpha) in the sera of Thai children hospitalized with dengue hemorrhagic fever (DHF) or dengue fever (DF) to examine the role of IFN alpha in dengue virus infections of humans. The percentage of patients who had detectable levels of IFN alpha ( \u3e or = 3 U/ml) was higher in patients with DHF (80%, P \u3c 0.001) and in patients with DF (60%, P \u3c 0.001) than in healthy Thai children (7%). The levels of IFN alpha were higher in patients with DHF and in patients with DF on the first few days after the onset of fever than in healthy Thai children. The average levels of IFN alpha in patients with DHF were high two days before defervescence, decreasing gradually until the day of defervescence. There was a subset of patients with DHF who had increasing levels of IFN alpha after defervescence. However, the levels of IFN alpha in patients with DF were not high after fever subsided. The levels of IFN alpha were not different among children with DHF grades 1, 2 and 3. Among patients with DHF, T lymphocytes were activated to a higher degree in high IFN alpha producers than in low IFN alpha producers. These results indicate that similarly high levels of IFN alpha are produced in vivo during the acute stages of DHF and DF, and that high levels of IFN alpha remain after fever subsides in some patients with DHF, but not in patients with DF

Queensland SharkSmart Drone Trial Final Report

Remotely Piloted Aircraft Systems, commonly called drones, provide a high-definition aerial view of a wide expanse of ocean, allowing the detection of potentially dangerous sharks in real-time, whilst having a negligible impact on the environment and non-target species. In addition, they are capable of spotting a range of marine hazards and can assist in beach rescue operations, thus providing numerous safety benefits for water users. The beaches of South-East Queensland (SEQ) have relatively good water clarity and a high level of visitation, making them an ideal location to test drones for detecting sharks and improving the safety of water users (Cardno, 2019). North Queensland beaches typically have lower water clarity, although it is important to test drones under these conditions to assess whether they can be effective at detecting sharks. The Queensland SharkSmart drone trial commenced on 19 September 2020, as a partnership between the Queensland Government Department of Agriculture and Fisheries (DAF) and Surf Life Saving Queensland (SLSQ). The trial was part of the Queensland Government’s commitment to research and trialling alternatives to traditional shark control measures. Drones were operated at two beaches on the Sunshine Coast (Alexandra Headland and Coolum North), two beaches on the Gold Coast (Southport Main Beach and Burleigh Beach) and one beach on North Stradbroke Island (NSI; Ocean beach) between 19 September 2020 and 4 October 2021. Additionally, to assess the effectiveness of drones at detecting sharks under the different environmental conditions found at North Queensland (NQ) beaches, drones were operated at Palm Cove, Cairns and Alma Bay, Magnetic Island, from 26 June 2021 to 31 October 2021. Drones were operated on weekends, public holidays and school holidays by SLSQ pilots, with two flights per hour from approximately 8am until midday. Flights lasted 15 - 20 minutes and followed a 400 m transect behind the surf break. All footage was collected in 4K and securely archived for later analysis with key operational and environmental data collected for every flight. When a shark was sighted, the drone pilot lowered the aircraft to determine the species and size while estimating distance of the animal from water users. Data analysis quantified the numbers of sharks sighted at each beach and the rate of sightings as a percentage across the whole trial from 19 September 2020 to 31 October 2021. Generalised Linear Mixed Models (GLMMs) were applied to quantify the influence of environmental and operational factors on the sightability (probability of a shark being sighted) of sharks. The movement tracks of sharks were mapped to analyse their behaviour and identify if there was clustering of movements in certain areas. Sighting rates from drones were also compared with shark catch in adjacent nets and drumlines deployed as part of the Queensland Shark Control Program (SCP)

Algorithm-driven activity-directed expansion of a series of antibacterial quinazolinones

Activity-directed synthesis (ADS) is a structure-blind, function driven approach that can drive the discovery of bioactive small molecules. In ADS, arrays of reactions are designed and executed, and the crude product mixtures are then directly screened to identify reactions that yield bioactive products. The design of subsequent reaction arrays is then informed by the hit reactions that are discovered. In this study, algorithms for reaction array design were developed in which the reactions to be executed were selected from a large set of virtual reactions; the reactions were selected on the basis of similarity to reactions known to yield bioactive products. The algorithms were harnessed to design arrays of photoredox-catalysed alkylation reactions whose crude products were then screened for inhibition of growth of S. aureus ATCC29213. It was demonstrated that the approach enabled expansion of a series of antibacterial quinazolinones. It is envisaged that such algorithms could ultimately enable fully autonomous activity-directed molecular discovery

Monitoring whales within the Reef 2050 Integrated Monitoring and Reporting Program: final report of the whales team in the megafauna expert group

Two species of great whales are commonly encountered on a seasonal basis in the Reef, the humpback, Megaptera novaeangliae, and the dwarf minke, Balaenoptera acutorostrata subsp. This report focuses on these two species, acknowledging that many other large and migratory whales utilise the Reef. Other limitations of this report include spatial and jurisdictional boundaries (i.e. a focus on specific information needs for agencies responsible for protection and management of values within the World Heritage Area). We acknowledge the need for more research to improve our overall understanding of these whale populations (e.g. stock structure and population connectivity through the south Pacific and Southern oceans), and the significance of risks to them through their extended habitat and range outside the World Heritage Area.An accessible copy of this report is not yet available from this repository, please contact [email protected] for more information