Three classes of ligands each bind to distinct sites on the orphan G protein-coupled receptor GPR84

Medium chain fatty acids can activate the pro-inflammatory receptor GPR84 but so also can molecules related to 3,3′-diindolylmethane. 3,3′-Diindolylmethane and decanoic acid acted as strong positive allosteric modulators of the function of each other and analysis showed the affinity of 3,3′-diindolylmethane to be at least 100 fold higher. Methyl decanoate was not an agonist at GPR84. This implies a key role in binding for the carboxylic acid of the fatty acid. Via homology modelling we predicted and confirmed an integral role of arginine172, located in the 2nd extracellular loop, in the action of decanoic acid but not of 3,3′-diindolylmethane. Exemplars from a patented series of GPR84 antagonists were able to block agonist actions of both decanoic acid and 3,3′-diindolylmethane at GPR84. However, although a radiolabelled form of a related antagonist, [3H]G9543, was able to bind with high affinity to GPR84, this was not competed for by increasing concentrations of either decanoic acid or 3,3′-diindolylmethane and was not affected adversely by mutation of arginine172. These studies identify three separable ligand binding sites within GPR84 and suggest that if medium chain fatty acids are true endogenous regulators then co-binding with a positive allosteric modulator would greatly enhance their function in physiological settings

Cestrum yellow leaf curling virus (CmYLCV) promoter: a new strong constitutive promoter for heterologous gene expression in a wide variety of crops

Appropriately regulated gene expression requires a suitable promoter. A number of promoters have been isolated and shown to be functional in plants, but only a few of them activate transcription of transgenes at high levels constitutively. We report here the cloning and characterization of a novel, constitutively expressed promoter isolated from Cestrum yellow leaf curling virus (CmYLCV), a double-stranded DNA plant pararetrovirus belonging to the Caulimoviridae family. The CmYLCV promoter is highly active in callus, meristems and vegetative and reproductive tissues in Arabidopsis thaliana, Nicotiana tabacum, Lycopersicon esculentum,Zea mays and Oryza sativa. Furthermore, the level of expression is comparable to, or higher than, that from the CaMV 35S, the 'ssuper-promoter' or the maize ubiquitin 1 promoters, three frequently used promoters in agricultural biotechnology. The heritable, strong and constitutive activity in both monocotyledonous and dicotyledonous plants, combined with the extremely narrow CmYLCV host range, makes the CmYLCV promoter an attractive tool for regulating transgene expression in a wide variety of plant specie

Development and Evaluation of Methods for Surveying Fish Populations in Nearshore Waters

Nearshore areas provide critical habitat for a range of fish species targeted by commercial and recreational fisheries, both of which make an important contribution to local economies in rural areas. However, established trawl survey methods are not suited to many nearshore areas, owing to shallow depths, obstructions on the sea bed or vulnerable habitats, so there is a lack of information on fish abundance in these areas. The aim of the present project was to develop and test survey methods applicable to Scottish inshore waters, focussing on baited underwater cameras, fish traps, systematic rod-and-line surveys and observations of fish bycatch in crustacean trap fisheries, and to carry out associated studies of fish movements. A lightweight baited underwater camera system was developed that could be deployed by two persons from inshore fishing vessels and small boats. The system consisted of a digital camera and strobes in underwater housings, mounted on a frame of aluminium alloy tubing, suspended above the seabed by sub-surface floats on one leg of a J-shaped mooring. The camera was baited with oily fish and a standardized 1 hour deployment period was used, to minimize variability in results due to changing tidal currents and bait degradation. Photographs were taken at 30 second intervals throughout the deployment period. On retrieval, the photographs were examined to derive indices of fish abundance, such as the time to first arrival of particular species (TFA) and the maximum number of individuals seen in the field of view at any time during the deployment (MaxN). The BUC system was developed and tested in the Firth of Clyde and then deployed at a range of other locations in Lamlash Bay, Arran, the Firth of Lorn, the Sound of Mull, Loch Sunart, Loch Etive, around Skye, Galloway and in Orkney. The BUC system was successfully deployed from a range of types of vessel in depths down to 40 m. Over thirty species of fish were recorded in total, including species of commercial interest, with lesser spotted dogfish, Scyliorhinus canicula, being the most commonly recorded. The number of species and indices of abundance were highest at sites on the Galloway peninsula. When compared within a single area, BUC detected more species than angling or fish traps, but less than in visual transects by SCUBA divers. BUC shows great potential as a cost-effective survey method, able to show relative differences in abundance between areas. It is likely that it would also be effective in detecting temporal trends, though this was outside the scope of the present project. A Norwegian design of collapsible cod trap, Roscoff traps designed for common prawns and Norway lobster creels were investigated as fish traps. There were differences in catch rates and species composition related to the trap design. Roscoff traps appeared to be suitable for sampling juvenile cod (Gadus morhua) in complex habitat in shallow water, whereas collapsible cod traps are suitable for larger fish, but need to be fished in greater numbers to obtain sufficient data. Creel fisheries were surveyed by questionnaire and by on-board catch sampling. A range of fish species is taken as bycatch in creels, with some obvious differences in species composition between crab fishing and Norway lobster fishing in relation to the depths and ground types fished. The present results suggest that the catch rates of commercial fish species may be too low for creeling to be a useful way of monitoring fish stocks, but sampling throughout the year in different areas would be desirable to assess this more fully. A small-scale pilot study in Galloway indicated some potential for rod-and-line surveys to generate useful information on the abundance of certain fishes. The Scottish Sea Angling Conservation Network and the Scottish Shark Tagging Project already collect information on catches of angling target species and on tagging and recaptures of tagged fish. This would be augmented by encouraging anglers to submit returns with an indication of fishing duration even when they have not caught anything. However, we were unsuccessful in recruiting volunteers to participate in a randomized angling survey. Further work is required to develop statistically robust angling surveys in which volunteer anglers would be willing to participate. Experience indicates that payment of expenses would be required for volunteers to agree to fish according to a survey protocol. To study movements of a species of interest to recreational sea anglers, spurdog (Squalus acanthias), ten specimens in Loch Etive were tagged with data storage tags designed to record water temperature and depth. To date, one tag has been recovered and the downloaded data shows an interesting pattern of nocturnal movements into shallow water. More information should become available when more of the tagged spurdog are recaptured. The following recommendations arise from the present study: To improve our understanding of baited methods of surveying fish and to develop improved estimates of abundance, modelling studies of bait odour dispersal and fish responses are required, building on previous work in this area. Further trials of baited underwater cameras at different sites and under different conditions are required to assess the degree of variability in the different types of abundance index that can be derived. Further work to compare different survey methods is required at sites with greater fish abundance, e.g. at sites around the Galloway peninsula. A BUC system with greater depth limit (e.g. 200 m) should be developed to extend the range of habitats in which it can be used to include other species of interest. Further work is required to assess the size and species selectivity of different designs of fish trap. An intensive pilot survey of an area of interest, such as an actual or proposed marine protected area, by BUC and fish traps would provide a good test of the ability of these methods to generate data of use to inshore fishery managers and conservation interests. Seasonal sampling of fish bycatch in Norway lobster and crab creel fisheries is desirable to further assess the potential for creel fisheries to be used to monitor fish populations. Ongoing analysis of recreational sea-angling catch and tagging records should be encouraged and supported by Marine Scotland. There should be continued engagement between recreational sea-anglers and fishery scientists in Marine Scotland and universities

Benchmarking real-time distributed object management systems for evolvable and adaptable command and control applications

Abstract This paper describes benchmarking for evolvable and adaptable real-time command and control systems Introduction MITRE's Evolvable Real-Time C3 initiative developed an approach that would enable current real-time systems to evolve into the systems of the future. We designed and implemented an infrastructure and data manager so that various applications could be hosted on the infrastructure. Then we completed a follow-on effort to design flexible adaptable distributed object management systems for command and control (C2) systems. Such an adaptable system would switch scheduling algorithms, policies, and protocols depending on the need and the environment. Both initiatives were carried out for the United States Air Force. One of the key contributions of our work is the investigation of real-time features for distributed object management systems. Partly as a result of our work we are now seeing various real-time distributed object management products being developed. In selecting a real-time distributed object management systems, we need to analyze various criteria. Therefore, we need benchmarking studies for realtime distributed object management systems. Although benchmarking systems such as Hartstone and Distributed Hartstone have been developed for middleware systems, these systems are not developed specifically for distributed object-based middleware. Since much of our work is heavily based on distributed objects, we developed benchmarking systems by adapting the Hartstone system. This paper describes out effort on developing benchmarks. In section 2 we discuss Distributed Hartstone. Then in section 3, we first provide background on the original Hartstone and DHartstone designs from SEI (Software Engineering Institute) and CMU (Carnegie Mellon University). We then describe our design and modification of DHartstone to incorporate the capability to benchmark real-time middleware in Section 4. Sections 5 and 6 describe the design of the benchmarking systems. For more details of our work on benchmarking and experimental results we refer to [MAUR98] and [MAUR99]. For background information of our work we refer t

Counter and Complicit Masculine Discourse Among Men’s Shed Members

Men’s Sheds is a growing international movement aimed at providing men with places and activities that facilitate social connectedness. Despite Men’s Sheds’ focus on males, little attention has been paid to masculinities within the specific context of these settings. The current study used a gender relations framework to explore the ways in which attendees discussed Men’s Sheds, with particular attention to discussions that were complicit and counter to traditional, hegemonic views of masculinity, and diverse positions in between these binaries. The data consisted of transcripts and field notes from four focus groups comprised of mostly older, White, retired male members of a Canadian shed (N = 22). The analysis revealed three overall themes: (1) focus on work, (2) independence, and (3) need for male-focused spaces. These themes and associated subthemes suggest that shed members ascribe to dominant masculine values and ideals, but also support more fluid and flexible views of masculinity. Implications are discussed for how working with an array of masculinities within the Men’s Sheds movement will be helpful with respect to their future growth in Canada and internationally

Using molecular data for epidemiological inference: assessing the prevalence of Trypanosoma brucei rhodesiense in Tsetse in Serengeti, Tanzania

Background: Measuring the prevalence of transmissible Trypanosoma brucei rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessing human disease risk and monitoring spatio-temporal trends and the impact of control interventions. Although an important epidemiological variable, identifying flies which carry transmissible infections is difficult, with challenges including low prevalence, presence of other trypanosome species in the same fly, and concurrent detection of immature non-transmissible infections. Diagnostic tests to measure the prevalence of T. b. rhodesiense in tsetse are applied and interpreted inconsistently, and discrepancies between studies suggest this value is not consistently estimated even to within an order of magnitude. Methodology/Principal Findings: Three approaches were used to estimate the prevalence of transmissible Trypanosoma brucei s.l. and T. b. rhodesiense in Glossina swynnertoni and G. pallidipes in Serengeti National Park, Tanzania: (i) dissection/microscopy; (ii) PCR on infected tsetse midguts; and (iii) inference from a mathematical model. Using dissection/microscopy the prevalence of transmissible T. brucei s.l. was 0% (95% CI 0–0.085) for G. swynnertoni and 0% (0–0.18) G. pallidipes; using PCR the prevalence of transmissible T. b. rhodesiense was 0.010% (0–0.054) and 0.0089% (0–0.059) respectively, and by model inference 0.0064% and 0.00085% respectively. Conclusions/Significance: The zero prevalence result by dissection/microscopy (likely really greater than zero given the results of other approaches) is not unusual by this technique, often ascribed to poor sensitivity. The application of additional techniques confirmed the very low prevalence of T. brucei suggesting the zero prevalence result was attributable to insufficient sample size (despite examination of 6000 tsetse). Given the prohibitively high sample sizes required to obtain meaningful results by dissection/microscopy, PCR-based approaches offer the current best option for assessing trypanosome prevalence in tsetse but inconsistencies in relating PCR results to transmissibility highlight the need for a consensus approach to generate meaningful and comparable data

Detection of Tetrodotoxin Shellfish Poisoning (TSP) Toxins and Causative Factors in Bivalve Molluscs from the UK

Publication history: Accepted - 28 August 2017; Published online - 30 August 2017.Tetrodotoxins (TTXs) are traditionally associated with the occurrence of tropical Pufferfish Poisoning. In recent years, however, TTXs have been identified in European bivalve mollusc shellfish, resulting in the need to assess prevalence and risk to shellfish consumers. Following the previous identification of TTXs in shellfish from southern England, this study was designed to assess the wider prevalence of TTXs in shellfish from around the coast of the UK. Samples were collected between 2014 and 2016 and subjected to analysis using HILIC-MS/MS. Results showed the continued presence of toxins in shellfish harvested along the coast of southern England, with the maximum concentration of total TTXs reaching 253 µg/kg. TTX accumulation was detected in Pacific oysters (Crassostrea gigas), native oysters (Ostrea edulis) common mussels (Mytilus edulis) and hard clams (Mercenaria mercenaria), but not found in cockles (Cerastoderma edule), razors (Ensis species) or scallops (Pecten maximus). Whilst the highest concentrations were quantified in samples harvested during the warmer summer months, TTXs were still evident during the winter. An assessment of the potential causative factors did not reveal any links with the phytoplankton species Prorocentrum cordatum, instead highlighting a greater level of risk in areas of shallow, estuarine waters with temperatures above 15 °CFunding from Cefas internal funding sources (Seedcorn, DP345B and DP402); and FS

A Non-Inferiority, Individually Randomized Trial of Intermittent Screening and Treatment versus Intermittent Preventive Treatment in the Control of Malaria in Pregnancy

BACKGROUND: The efficacy of intermittent preventive treatment for malaria with sulfadoxine-pyrimethamine (IPTp-SP) in pregnancy is threatened in parts of Africa by the emergence and spread of resistance to SP. Intermittent screening with a rapid diagnostic test (RDT) and treatment of positive women (ISTp) is an alternative approach. METHODS AND FINDINGS: An open, individually randomized, non-inferiority trial of IPTp-SP versus ISTp was conducted in 5,354 primi- or secundigravidae in four West African countries with a low prevalence of resistance to SP (The Gambia, Mali, Burkina Faso and Ghana). Women in the IPTp-SP group received SP on two or three occasions whilst women in the ISTp group were screened two or three times with a RDT and treated if positive for malaria with artemether-lumefantrine (AL). ISTp-AL was non-inferior to IPTp-SP in preventing low birth weight (LBW), anemia and placental malaria, the primary trial endpoints. The prevalence of LBW was 15.1% and 15.6% in the IPTp-SP and ISTp-AL groups respectively (OR = 1.03 [95% CI: 0.88, 1.22]). The mean hemoglobin concentration at the last clinic attendance before delivery was 10.97g/dL and 10.94g/dL in the IPTp-SP and ISTp-AL groups respectively (mean difference: -0.03 g/dL [95% CI: -0.13, +0.06]). Active malaria infection of the placenta was found in 24.5% and in 24.2% of women in the IPTp-SP and ISTp-AL groups respectively (OR = 0.95 [95% CI 0.81, 1.12]). More women in the ISTp-AL than in the IPTp-SP group presented with malaria parasitemia between routine antenatal clinics (310 vs 182 episodes, rate difference: 49.4 per 1,000 pregnancies [95% CI 30.5, 68.3], but the number of hospital admissions for malaria was similar in the two groups. CONCLUSIONS: Despite low levels of resistance to SP in the study areas, ISTp-AL performed as well as IPTp-SP. In the absence of an effective alternative medication to SP for IPTp, ISTp-AL is a potential alternative to IPTp in areas where SP resistance is high. It may also have a role in areas where malaria transmission is low and for the prevention of malaria in HIV positive women receiving cotrimoxazole prophylaxis in whom SP is contraindicated. TRIAL REGISTRATION: ClinicalTrials.gov NCT01084213 Pan African Clinical trials Registry PACT201202000272122