222 research outputs found

    GPCR Genes Are Preferentially Retained after Whole Genome Duplication

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    One of the most interesting questions in biology is whether certain pathways have been favored during evolution, and if so, what properties could cause such a preference. Due to the lack of experimental evidence, whether select gene families have been preferentially retained over time after duplication in metazoan organisms remains unclear. Here, by syntenic mapping of nonchemosensory G protein-coupled receptor genes (nGPCRs which represent half the receptome for transmembrane signaling) in the vertebrate genomes, we found that, as opposed to the 8–15% retention rate for whole genome duplication (WGD)-derived gene duplicates in the entire genome of pufferfish, greater than 27.8% of WGD-derived nGPCRs which interact with a nonpeptide ligand were retained after WGD in pufferfish Tetraodon nigroviridis. In addition, we show that concurrent duplication of cognate ligand genes by WGD could impose selection of nGPCRs that interact with a polypeptide ligand. Against less than 2.25% probability for parallel retention of a pair of WGD-derived ligands and a pair of cognate receptor duplicates, we found a more than 8.9% retention of WGD-derived ligand-nGPCR pairs–threefold greater than one would surmise. These results demonstrate that gene retention is not uniform after WGD in vertebrates, and suggest a Darwinian selection of GPCR-mediated intercellular communication in metazoan organisms

    The Influence of Meteorology on the Spread of Influenza: Survival Analysis of an Equine Influenza (A/H3N8) Outbreak

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    The influences of relative humidity and ambient temperature on the transmission of influenza A viruses have recently been established under controlled laboratory conditions. The interplay of meteorological factors during an actual influenza epidemic is less clear, and research into the contribution of wind to epidemic spread is scarce. By applying geostatistics and survival analysis to data from a large outbreak of equine influenza (A/H3N8), we quantified the association between hazard of infection and air temperature, relative humidity, rainfall, and wind velocity, whilst controlling for premises-level covariates. The pattern of disease spread in space and time was described using extraction mapping and instantaneous hazard curves. Meteorological conditions at each premises location were estimated by kriging daily meteorological data and analysed as time-lagged time-varying predictors using generalised Cox regression. Meteorological covariates time-lagged by three days were strongly associated with hazard of influenza infection, corresponding closely with the incubation period of equine influenza. Hazard of equine influenza infection was higher when relative humidity was <60% and lowest on days when daily maximum air temperature was 20–25°C. Wind speeds >30 km hour−1 from the direction of nearby infected premises were associated with increased hazard of infection. Through combining detailed influenza outbreak and meteorological data, we provide empirical evidence for the underlying environmental mechanisms that influenced the local spread of an outbreak of influenza A. Our analysis supports, and extends, the findings of studies into influenza A transmission conducted under laboratory conditions. The relationships described are of direct importance for managing disease risk during influenza outbreaks in horses, and more generally, advance our understanding of the transmission of influenza A viruses under field conditions

    Emerging Technologies for the Detection of Rabies Virus: Challenges and Hopes in the 21st Century

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    The diagnosis of rabies is routinely based on clinical and epidemiological information, especially when exposures are reported in rabies-endemic countries. Diagnostic tests using conventional assays that appear to be negative, even when undertaken late in the disease and despite the clinical diagnosis, have a tendency, at times, to be unreliable. These tests are rarely optimal and entirely dependent on the nature and quality of the sample supplied. In the course of the past three decades, the application of molecular biology has aided in the development of tests that result in a more rapid detection of rabies virus. These tests enable viral strain identification from clinical specimens. Currently, there are a number of molecular tests that can be used to complement conventional tests in rabies diagnosis. Indeed the challenges in the 21st century for the development of rabies diagnostics are not of a technical nature; these tests are available now. The challenges in the 21st century for diagnostic test developers are two-fold: firstly, to achieve internationally accepted validation of a test that will then lead to its acceptance by organisations globally. Secondly, the areas of the world where such tests are needed are mainly in developing regions where financial and logistical barriers prevent their implementation. Although developing countries with a poor healthcare infrastructure recognise that molecular-based diagnostic assays will be unaffordable for routine use, the cost/benefit ratio should still be measured. Adoption of rapid and affordable rabies diagnostic tests for use in developing countries highlights the importance of sharing and transferring technology through laboratory twinning between the developed and the developing countries. Importantly for developing countries, the benefit of molecular methods as tools is the capability for a differential diagnosis of human diseases that present with similar clinical symptoms. Antemortem testing for human rabies is now possible using molecular techniques. These barriers are not insurmountable and it is our expectation that if such tests are accepted and implemented where they are most needed, they will provide substantial improvements for rabies diagnosis and surveillance. The advent of molecular biology and new technological initiatives that combine advances in biology with other disciplines will support the development of techniques capable of high throughput testing with a low turnaround time for rabies diagnosis

    Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

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    BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

    Lawson criterion for ignition exceeded in an inertial fusion experiment

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    For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

    APPLICATIONS OF SURFACE SENSITIVE TECHNIQUES IN THE STUDY OF PHOTOCHEMICAL PROCESSING AT THE SOLID-GAS INTERFACE.

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    The applications of surface sensitive techniques to chemical problems arising in photochemical processing are considered. Both their use in ex situ and in situ modes are described. Results for three photochemical processes are presented dealing with the chemical origins of periodic ripples in LCVD deposits, W metallisation from WF//6 vapour and photo-enhanced etching

    METAL DEPOSITION ON SILICON: IN SITU SURFACE STUDIES.

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    In order to investigate surface chemistry in greater detail an approach has been adopted whereby thin film formation is examined in situ using the powerful techniques of surface science. In this abstract the results of pyrolytic, photolytic and electron beam deposition studies of Fe from Fe(CO)//5 on Si (100) are summarized. All experiments were carried out in a stainless steel ultra-high-vacuum chamber equipped for LEED, AES and thermal desorption experiments. Clean Si surfaces were produced in vacuo and AES showed less than 0. 2% surface contamination

    Electrochemical detection of indoles at diamond electrodes

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    Indoles represent an important class of chemical compounds, of biological significance, and various attempts have been made to develop electrochemical sensors for their detection. In general, this has failed because of the electrode fouling which tends to occur when conventional electrode materials are employed, so we have explored the use of diamond electrodes, in view of their known resistance to electrode poisoning. High phase purity boron-doped diamond electrodes show no detectable oxidative signal when used in solutions containing indole-3-methanol or 1-methyl indole. However, indole oxidation at electrode potentials greater than 0.7 V vs. SCE is seen if lower purity diamond or nanodiamond electrodes are employed. Electrode fouling is found to be problematic, but significantly better than at pyrolytic graphite electrodes. The oxidation of tryptophan at high phase purity diamond electrodes is seen, indicating that in general the indole oxidation chemistry is dependent both on the type of diamond electrode used, and the particular indole involved. Sensitive detection of tryptophan at micromolar concentrations is observed without electrode fouling, although electrode passivation is seen in concentrated tryptophan solutions. © 2005 WILEY-VCH Verlag GmbH and Co. KGaA

    Permselective properties of polystyrene opal films at diamond electrode surfaces.

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    The permselective properties of stable opal films formed by polystyrene nanospheres on boron-doped diamond (BDD) electrodes were studied for the first time by means of electrochemical voltammetric and impedance techniques. Films formed from spheres with a diameter above 200 nm are highly porous and have little influence on electrochemical properties. In contrast, porous films formed from 50 nm spheres have a selective influence on the electrochemistry observed, providing an enhancement in the redox peak current for neutral (ferrocenemethanol, dopamine) and positively-charged redox probe mediators (Ru(NH(3))(6)(3+)) and suppressing the current due to a negatively-charged redox species Fe(CN)(6)(4-). This is because the latter is repelled from the film, whereas the former are selectively partitioned within it. Partition coefficients, film permeability and diffusion coefficients of species within the polystyrene opal layer are determined. It is shown that a Langmuir isotherm analysis for adsorption on the polystyrene sphere surface can describe successfully the incorporation of ferrocenemethanol and Ru(NH(3))(6)(3+) within the thin film, with Gibb's free energies (DeltaG(o)) of adsorption in the range of -27 to 28 kJ mol(-1). Apart from influencing the magnitude of the detected electrochemical response, it is also shown the opal film increases the resistance to electrode fouling by the reaction products formed by the oxidation of dopamine. Electrochemical impedance measurements further illustrate the effects of the polystyrene layer
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