6,784 research outputs found

    Ligand-dependent opening of the multiple AMPA receptor conductance states: a concerted model

    Full text link
    Modulation of the properties of AMPA receptors at the post-synaptic membrane is one of the main suggested mechanisms behind synaptic plasticity in the central nervous system of vertebrates. Electrophysiological recordings of single channels stimulated with agonists showed that both recombinant and native AMPA receptors visit multiple conductance states in an agonist concentration dependent manner. We propose an allosteric model of the multiple conductance states based on concerted conformational transitions of the four subunits, as an iris diaphragm. Our model predicts that the thermodynamic behaviour of the conductance states upon full and partial agonist stimulations can be described with increased affinity of receptors as they progress to higher conductance states. The model also predicts existence of AMPA receptors in non-liganded conductive substates. However, spontaneous openings probability decreases with increasing conductances. Finally, we predict that the large conductance states are stabilized within the rise phase of a whole-cell EPSC in glutamatergic hippocampal neurons. Our model provides a mechanistic link between ligand concentration and conductance states that can explain thermodynamic and kinetic features of AMPA receptor gating.Comment: 4 figures, models available on demand. They will be published by BioModels Database upon publication of the articl

    Iron supplementation to treat anaemia in adult critical care patients: a systematic review and meta-analysis

    Get PDF
    Anaemia affects 60-80 % of patients admitted to intensive care units (ICUs). Allogeneic red blood cell (RBC) transfusions remain the mainstay of treatment for anaemia but are associated with risks and are costly. Our objective was to assess the efficacy and safety of iron supplementation by any route, in anaemic patients in adult ICUs.Electronic databases (CENTRAL, MEDLINE, EMBASE) were searched through March 2016 for randomized controlled trials (RCT)s comparing iron by any route with placebo/no iron. Primary outcomes were red blood cell transfusions and mean haemoglobin concentration. Secondary outcomes included mortality, infection, ICU and hospital length of stay, mean difference (MD) in iron biomarkers, health-related quality of life and adverse events.Five RCTs recruiting 665 patients met the inclusion criteria; intravenous iron was tested in four of the RCTs. There was no difference in allogeneic RBC transfusion requirements (relative risk 0.87, 95 % confidence interval (CI) 0.70 to 1.07, p = 0.18, five trials) or mean number of RBC units transfused (MD -0.45, 95 % CI -1.34 to 0.43, p = 0.32, two trials) in patients receiving or not receiving iron. Similarly, there was no difference between groups in haemoglobin at short-term (up to 10 days) (MD -0.25, 95 % CI -0.79 to 0.28, p = 0.35, three trials) or mid-term follow up (last measured time point in hospital or end of trial) (MD 0.21, 95 % CI -0.13 to 0.55, p = 0.23, three trials). There was no difference in secondary outcomes of mortality, in-hospital infection, or length of stay. Risk of bias was generally low although three trials had high risk of attrition bias; only one trial had low risk of bias across all domains.Iron supplementation does not reduce RBC transfusion requirements in critically ill adults, but there is considerable heterogeneity between trials in study design, nature of interventions, and outcomes. Well-designed trials are needed to investigate the optimal iron dosing regimens and strategies to identify which patients are most likely to benefit from iron, together with patient-focused outcomes.PROSPERO International prospective register of systematic reviews CRD42015016627 . Registered 2 March 2015

    Incorporation of the microencapsulated antimicrobial agent phytoncide into denture base resin

    Get PDF
    Background This study aimed to fabricate a denture base resin (DBR) containing phytoncide microcapsules (PTMCs) and determine the mechanical properties of the resin and antifungal activity. Methods Fifty‐four heat cured rectangular DBR specimens (64 x 10 x 3.3 ± 0.2 mm) containing nine concentrations of PTMC between 0 ‐ 5% (wt/wt) were fabricated and subjected to a three‐point bending test. A phytoncide release bioassay was developed using DBR containing 0% and 2.5% PTMCs (wt/wt) in a 24 well‐plate assay with incubation of Porphyromonas gingivalis at 37°C for 74 h. The antifungal activity of PTMCs against Candida albicans, in a pH 5.5 acidic environment was determined in a plate assay. Results Flexural strength decreased with increasing PTMC concentration from 97.58 ± 4.79 MPa for the DBR alone to 53.66 ± 2.46 MPa for DBR containing 5.0% PTMC. No release of phytoncide from the PTMCs in the DBR was detected at pH 7.4. The PTMCs had a minimal inhibitory concentration of 2.6% (wt/vol) against C. albicans at pH 5.5. Conclusions PTMCs can be added to DBR 2.5% (wt/wt) without adversely affecting flexural strength. PTMCs released the antimicrobial agent at pH 5.5 at concentrations sufficient to inhibit the growth of the C. albicans

    Characteristics and drivers of high-altitude ladybird flight: insights from vertical-looking entomological radar

    Get PDF
    Understanding the characteristics and drivers of dispersal is crucial for predicting population dynamics, particularly in range-shifting species. Studying long-distance dispersal in insects is challenging, but recent advances in entomological radar offer unique insights. We analysed 10 years of radar data collected at Rothamsted Research, U.K., to investigate characteristics (altitude, speed, seasonal and annual trends) and drivers (aphid abundance, air temperature, wind speed and rainfall) of high-altitude flight of the two most abundant U.K. ladybird species (native Coccinella septempunctata and invasive Harmonia axyridis). These species cannot be distinguished in the radar data since their reflectivity signals overlap, and they were therefore analysed together. However, their signals do not overlap with other, abundant insects so we are confident they constitute the overwhelming majority of the analysed data. The target species were detected up to ~1100 m above ground level, where displacement speeds of up to ~60 km/h were recorded, however most ladybirds were found between ~150 and 500 m, and had a mean displacement of 30 km/h. Average flight time was estimated, using tethered flight experiments, to be 36.5 minutes, but flights of up to two hours were observed. Ladybirds are therefore potentially able to travel 18 km in a "typical" high-altitude flight, but up to 120 km if flying at higher altitudes, indicating a high capacity for long-distance dispersal. There were strong seasonal trends in ladybird abundance, with peaks corresponding to the highest temperatures of mid-summer, and warm air temperature was the key driver of ladybird flight. Climatic warming may therefore increase the potential for long-distance dispersal in these species. Low aphid abundance was a second significant factor, highlighting the important role of aphid population dynamics in ladybird dispersal. This research illustrates the utility of radar for studying high-altitude insect flight and has important implications for predicting long-distance dispersal. © 2013 Jeffries et al

    A global analysis of genetic interactions in Caenorhabditis elegans

    Get PDF
    Abstract Background Understanding gene function and genetic relationships is fundamental to our efforts to better understand biological systems. Previous studies systematically describing genetic interactions on a global scale have either focused on core biological processes in protozoans or surveyed catastrophic interactions in metazoans. Here, we describe a reliable high-throughput approach capable of revealing both weak and strong genetic interactions in the nematode Caenorhabditis elegans. Results We investigated interactions between 11 'query' mutants in conserved signal transduction pathways and hundreds of 'target' genes compromised by RNA interference (RNAi). Mutant-RNAi combinations that grew more slowly than controls were identified, and genetic interactions inferred through an unbiased global analysis of the interaction matrix. A network of 1,246 interactions was uncovered, establishing the largest metazoan genetic-interaction network to date. We refer to this approach as systematic genetic interaction analysis (SGI). To investigate how genetic interactions connect genes on a global scale, we superimposed the SGI network on existing networks of physical, genetic, phenotypic and coexpression interactions. We identified 56 putative functional modules within the superimposed network, one of which regulates fat accumulation and is coordinated by interactions with bar-1(ga80), which encodes a homolog of β-catenin. We also discovered that SGI interactions link distinct subnetworks on a global scale. Finally, we showed that the properties of genetic networks are conserved between C. elegans and Saccharomyces cerevisiae, but that the connectivity of interactions within the current networks is not. Conclusions Synthetic genetic interactions may reveal redundancy among functional modules on a global scale, which is a previously unappreciated level of organization within metazoan systems. Although the buffering between functional modules may differ between species, studying these differences may provide insight into the evolution of divergent form and function

    Developing and enhancing biodiversity monitoring programmes: a collaborative assessment of priorities

    Get PDF
    1.Biodiversity is changing at unprecedented rates, and it is increasingly important that these changes are quantified through monitoring programmes. Previous recommendations for developing or enhancing these programmes focus either on the end goals, that is the intended use of the data, or on how these goals are achieved, for example through volunteer involvement in citizen science, but not both. These recommendations are rarely prioritized. 2.We used a collaborative approach, involving 52 experts in biodiversity monitoring in the UK, to develop a list of attributes of relevance to any biodiversity monitoring programme and to order these attributes by their priority. We also ranked the attributes according to their importance in monitoring biodiversity in the UK. Experts involved included data users, funders, programme organizers and participants in data collection. They covered expertise in a wide range of taxa. 3.We developed a final list of 25 attributes of biodiversity monitoring schemes, ordered from the most elemental (those essential for monitoring schemes; e.g. articulate the objectives and gain sufficient participants) to the most aspirational (e.g. electronic data capture in the field, reporting change annually). This ordered list is a practical framework which can be used to support the development of monitoring programmes. 4.People's ranking of attributes revealed a difference between those who considered attributes with benefits to end users to be most important (e.g. people from governmental organizations) and those who considered attributes with greatest benefit to participants to be most important (e.g. people involved with volunteer biological recording schemes). This reveals a distinction between focussing on aims and the pragmatism in achieving those aims. 5.Synthesis and applications. The ordered list of attributes developed in this study will assist in prioritizing resources to develop biodiversity monitoring programmes (including citizen science). The potential conflict between end users of data and participants in data collection that we discovered should be addressed by involving the diversity of stakeholders at all stages of programme development. This will maximize the chance of successfully achieving the goals of biodiversity monitoring programmes

    Power laws of complex systems from Extreme physical information

    Full text link
    Many complex systems obey allometric, or power, laws y=Yx^{a}. Here y is the measured value of some system attribute a, Y is a constant, and x is a stochastic variable. Remarkably, for many living systems the exponent a is limited to values +or- n/4, n=0,1,2... Here x is the mass of a randomly selected creature in the population. These quarter-power laws hold for many attributes, such as pulse rate (n=-1). Allometry has, in the past, been theoretically justified on a case-by-case basis. An ultimate goal is to find a common cause for allometry of all types and for both living and nonliving systems. The principle I - J = extrem. of Extreme physical information (EPI) is found to provide such a cause. It describes the flow of Fisher information J => I from an attribute value a on the cell level to its exterior observation y. Data y are formed via a system channel function y = f(x,a), with f(x,a) to be found. Extremizing the difference I - J through variation of f(x,a) results in a general allometric law f(x,a)= y = Yx^{a}. Darwinian evolution is presumed to cause a second extremization of I - J, now with respect to the choice of a. The solution is a=+or-n/4, n=0,1,2..., defining the particular powers of biological allometry. Under special circumstances, the model predicts that such biological systems are controlled by but two distinct intracellular information sources. These sources are conjectured to be cellular DNA and cellular transmembrane ion gradient

    Mapping species distributions: A comparison of skilled naturalist and lay citizen science recording

    Get PDF
    To assess the ability of traditional biological recording schemes and lay citizen science approaches to gather data on species distributions and changes therein, we examined bumblebee records from the UK’s national repository (National Biodiversity Network) and from BeeWatch. The two recording approaches revealed similar relative abundances of bumblebee species but different geographical distributions. For the widespread common carder (Bombus pascuorum), traditional recording scheme data were patchy, both spatially and temporally, reflecting active record centre rather than species distribution. Lay citizen science records displayed more extensive geographic coverage, reflecting human population density, thus offering better opportunities to account for recording effort. For the rapidly spreading tree bumblebee (Bombus hypnorum), both recording approaches revealed similar distributions due to a dedicated mapping project which overcame the patchy nature of naturalist records. We recommend, where possible, complementing skilled naturalist recording with lay citizen science programmes to obtain a nation-wide capability, and stress the need for timely uploading of data to the national repository
    corecore