2,558 research outputs found

    Acute insult of ammonia leads to calcium-dependent glutamate release from cultured astrocytes, an effect of pH

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    Hyperammonemia is a key factor in the pathogenesis of hepatic encephalopathy (HE) as well as other metabolic encephalopathies, such as those associated with inherited disorders of urea cycle enzymes and in Reye's syndrome. Acute HE results in increased brain ammonia (up to 5 mM), astrocytic swelling, and altered glutamatergic function. In the present study, using fluorescence imaging techniques, acute exposure (10 min) of ammonia (NH4+/NH3) to cultured astrocytes resulted in a concentration-dependent, transient increase in [Ca2+]i. This calcium transient was due to release from intracellular calcium stores, since the response was thapsigargin-sensitive and was still observed in calcium-free buffer. Using an enzyme-linked fluorescence assay, glutamate release was measured indirectly via the production of NADH (a naturally fluorescent product when excited with UV light). NH4+/NH3 (5 mM) stimulated a calcium-dependent glutamate release from cultured astrocytes, which was inhibited after preincubation with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester but unaffected after preincubation with glutamate transport inhibitors dihydrokainate and DL-threo-beta-benzyloxyaspartate. NH4+/NH3 (5 mM) also induced a transient intracellular alkaline shift. To investigate whether the effects of NH4+/NH3 were mediated by an increase in pH(i), we applied trimethylamine (TMA+/TMA) as another weak base. TMA+/TMA (5 mM) induced a similar transient increase in both pH(i) and [Ca2+]i (mobilization from intracellular calcium stores) and resulted in calcium-dependent release of glutamate. These results indicate that an acute exposure to ammonia, resulting in cytosolic alkalinization, leads to calcium-dependent glutamate release from astrocytes. A deregulation of glutamate release from astrocytes by ammonia could contribute to glutamate dysfunction consistently observed in acute HE

    The RCSB Protein Data Bank: views of structural biology for basic and applied research and education.

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    The RCSB Protein Data Bank (RCSB PDB, http://www.rcsb.org) provides access to 3D structures of biological macromolecules and is one of the leading resources in biology and biomedicine worldwide. Our efforts over the past 2 years focused on enabling a deeper understanding of structural biology and providing new structural views of biology that support both basic and applied research and education. Herein, we describe recently introduced data annotations including integration with external biological resources, such as gene and drug databases, new visualization tools and improved support for the mobile web. We also describe access to data files, web services and open access software components to enable software developers to more effectively mine the PDB archive and related annotations. Our efforts are aimed at expanding the role of 3D structure in understanding biology and medicine

    Public health impact and cost-effectiveness of intranasal live attenuated influenza vaccination of children in Germany

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    Damm O, Eichner M, Rose MA, et al. Public health impact and cost-effectiveness of intranasal live attenuated influenza vaccination of children in Germany. The European Journal of Health Economics. 2015;16(5):471-488.In 2011, intranasally administered live attenuated influenza vaccine (LAIV) was approved in the EU for prophylaxis of seasonal influenza in 2-17-year-old children. Our objective was to estimate the potential epidemiological impact and cost-effectiveness of an LAIV-based extension of the influenza vaccination programme to healthy children in Germany. An age-structured dynamic model of influenza transmission was developed and combined with a decision-tree to evaluate different vaccination strategies in the German health care system. Model inputs were based on published literature or were derived by expert consulting using the Delphi technique. Unit costs were drawn from German sources. Under base-case assumptions, annual routine vaccination of children aged 2-17 years with LAIV assuming an uptake of 50 % would prevent, across all ages, 16 million cases of symptomatic influenza, over 600,000 cases of acute otitis media, nearly 130,000 cases of community-acquired pneumonia, nearly 1.7 million prescriptions of antibiotics and over 165,000 hospitalisations over 10 years. The discounted incremental cost-effectiveness ratio was a,not sign1,228 per quality-adjusted life year gained from a broad third-party payer perspective (including reimbursed direct costs and specific transfer payments), when compared with the current strategy of vaccinating primarily risk groups with the conventional trivalent inactivated vaccine. Inclusion of patient co-payments and indirect costs in terms of productivity losses resulted in discounted 10-year cost savings of a,not sign3.4 billion. In conclusion, adopting universal influenza immunisation of healthy children and adolescents would lead to a substantial reduction in influenza-associated disease at a reasonable cost to the German statutory health insurance system. On the basis of the epidemiological and health economic simulation results, a recommendation of introducing annual routine influenza vaccination of children 2-17 years of age might be taken into consideration

    Simulation and experiment of gas diffusion in a granular bed

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    The diffusion of gas through porous material is important to understand the physical processes underlying cometary activity. We study the diffusion of a rarefied gas (Knudsen regime) through a packed bed of monodisperse spheres via experiments and numerical modelling, providing an absolute value of the diffusion coefficient and compare it to published analytical models. The experiments are designed to be directly comparable to numerical simulations, by using precision steel beads, simple geometries, and a trade-off of the sample size between small boundary effects and efficient computation. For direct comparison, the diffusion coefficient is determined in Direct Simulation Monte Carlo (DSMC) simulations, yielding a good match with experiments. This model is further-on used on a microscopic scale, which cannot be studied in experiments, to determine the mean path of gas molecules and its distribution, and compare it against an analytical model. Scaling with sample properties (particle size, porosity) and gas properties (molecular mass, temperature) is consistent with analytical models. As predicted by these, results are very sensitive on sample porosity and we find that a tortuosity q(ε)q(\varepsilon) depending linearly on the porosity ε\varepsilon can well reconcile the analytical model with experiments and simulations. Mean paths of molecules are close to those described in the literature, but their distribution deviates from the expectation for small path lengths. The provided diffusion coefficients and scaling laws are directly applicable to thermophysical models of idealised cometary material.Comment: accepted by MNRA

    Diversity Of Crustacean Isopod In Bangka Island Of North Sulawesi

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    Information about marine isopods in Indonesian water is scarce. This research aimed to inventory isopods in nearshore habitats of Northern Sulawesi using a morphological approach to identify the species. Sampling was done in several spots in Bangka Island considering three different habitats: coral rubble, mangrove roots, and seagrass beds. These habitats are known to be suitable for isopods to feed, reproduce, and hide from bigger predators. There is 7 group of Isopod found in totals, such as Anthuridea, Asellota, Bopyridae, Cirolanidae, Gnathiidae, Limnoriidea, and Sphaeromatidea. In the family of Anthuridae, there are 2 suspected new species and required further identification.Keywords: Marine Isopod, Ecology, Bangka Island, North Sulawesi.AbstrakInformasi mengenai isopoda laut di perairan Indonesia masih sangat sedikit. Penelitian ini bertujuan untuk menginventarisasi isopoda di habitat dekat pantai Sulawesi Utara menggunakan pendekatan morfologi untuk mengidentifikasi spesies. Pengambilan sampel dilakukan di beberapa titik di Pulau Bangka dengan pertimbangan tiga jenis habitat berbeda: serpihan karang, akar mangrove, dan padang lamun. Habitat tersebut merupakan tempat isopoda mencari makan, bereproduksi, dan bersembunyi dari predator. Dari hasil identifikasi ditemukan 7 kelompok isopoda, yakni  Anthuridea, Asellota, Bopyridae, Cirolanidae, Gnathiidae, Limnoriidea, dan Sphaeromatidea. Diduga ada 2 species yang baru di kelompok Anthuridae yang masih perlu penelitian lebih lanjut.Kata kunci: Isopoda Laut,  Ekologi, Pulau Bangka, Sulawesi Utara

    Local challenges and successes associated with transitioning to sustainable food system practices for a West Australian context: Multi-sector stakeholder perceptions

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    Large-scale food system practices have diminished soil and water quality and negatively impacted climate change. Yet, numerous opportunities exist to harness food system practices that will ensure better outcomes for human health and ecosystems. The objective of this study was to consider food Production, Processing, Access and Consumption domains, and for each determine the challenges and successes associated with progressing towards a sustainable food system. A workshop engaging 122 participants including producers, consultants, consumers, educators, funders, scientists, media, government and industry representatives, was conducted in Perth, Western Australia. A thematic analysis of statements (Successes (n = 170) or Challenges (n = 360)) captured, revealed issues of scale, knowledge and education, economics, consumerism, big food, environmental/sustainability, communication, policies and legislation, and technology and innovations. Policy recommendations included greater investment into research in sustainable agriculture (particularly the evidentiary basis for regenerative agriculture), land preservation, and supporting farmers to overcome high infrastructure costs and absorb labour costs. Policy, practice and research recommendations included focusing on an integrated food systems approach with multiple goals, food system actors working collaboratively to reduce challenges and undertaking more research to further the regenerative agriculture evidence

    Development and optimization of the Suna trap as a tool for mosquito monitoring and control

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    Background Monitoring of malaria vector populations provides information about disease transmission risk, as well as measures of the effectiveness of vector control. The Suna trap is introduced and evaluated with regard to its potential as a new, standardized, odour-baited tool for mosquito monitoring and control. Methods Dual-choice experiments with female Anopheles gambiae sensu lato in a laboratory room and semi-field enclosure, were used to compare catch rates of odour-baited Suna traps and MM-X traps. The relative performance of the Suna trap, CDC light trap and MM-X trap as monitoring tools was assessed inside a human-occupied experimental hut in a semi-field enclosure. Use of the Suna trap as a tool to prevent mosquito house entry was also evaluated in the semi-field enclosure. The optimal hanging height of Suna traps was determined by placing traps at heights ranging from 15 to 105 cm above ground outside houses in western Kenya. Results In the laboratory the mean proportion of An. gambiae s.l. caught in the Suna trap was 3.2 times greater than the MM-X trap (P <0.001), but the traps performed equally in semi-field conditions (P = 0.615). As a monitoring tool , the Suna trap outperformed an unlit CDC light trap (P <0.001), but trap performance was equal when the CDC light trap was illuminated (P = 0.127). Suspending a Suna trap outside an experimental hut reduced entry rates by 32.8% (P <0.001). Under field conditions, suspending the trap at 30 cm above ground resulted in the greatest catch sizes (mean 25.8 An. gambiae s.l. per trap night). Conclusions The performance of the Suna trap equals that of the CDC light trap and MM-X trap when used to sample An. gambiae inside a human-occupied house under semi-field conditions. The trap is effective in sampling mosquitoes outside houses in the field, and the use of a synthetic blend of attractants negates the requirement of a human bait. Hanging a Suna trap outside a house can reduce An. gambiae house entry and its use as a novel tool for reducing malaria transmission risk will be evaluated in peri-domestic settings in sub-Saharan Africa

    Balancing Selection at the Tomato RCR3 Guardee Gene Family Maintains Variation in Strength of Pathogen Defense

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    Coevolution between hosts and pathogens is thought to occur between interacting molecules of both species. This results in the maintenance of genetic diversity at pathogen antigens (or so-called effectors) and host resistance genes such as the major histocompatibility complex (MHC) in mammals or resistance (R) genes in plants. In plant-pathogen interactions, the current paradigm posits that a specific defense response is activated upon recognition of pathogen effectors via interaction with their corresponding R proteins. According to the''Guard-Hypothesis,'' R proteins (the ``guards'') can sense modification of target molecules in the host (the ``guardees'') by pathogen effectors and subsequently trigger the defense response. Multiple studies have reported high genetic diversity at R genes maintained by balancing selection. In contrast, little is known about the evolutionary mechanisms shaping the guardee, which may be subject to contrasting evolutionary forces. Here we show that the evolution of the guardee RCR3 is characterized by gene duplication, frequent gene conversion, and balancing selection in the wild tomato species Solanum peruvianum. Investigating the functional characteristics of 54 natural variants through in vitro and in planta assays, we detected differences in recognition of the pathogen effector through interaction with the guardee, as well as substantial variation in the strength of the defense response. This variation is maintained by balancing selection at each copy of the RCR3 gene. Our analyses pinpoint three amino acid polymorphisms with key functional consequences for the coevolution between the guardee (RCR3) and its guard (Cf-2). We conclude that, in addition to coevolution at the ``guardee-effector'' interface for pathogen recognition, natural selection acts on the ``guard-guardee'' interface. Guardee evolution may be governed by a counterbalance between improved activation in the presence and prevention of auto-immune responses in the absence of the corresponding pathogen
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