274 research outputs found

    Reproduction in risky environments: the role of invasive egg predators in ladybird laying strategies

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    This is the final version of the article. Available from PLOS via the DOI in this record.We have made the data for this publication freely available from the University of Exeter Repository: URL http://hdl.handle.net/10871/18252.Reproductive environments are variable and the resources available for reproduction are finite. If reliable cues about the environment exist, mothers can alter offspring phenotype in a way that increases both offspring and maternal fitness ('anticipatory maternal effects'-AMEs). Strategic use of AMEs is likely to be important in chemically defended species, where the risk of offspring predation may be modulated by maternal investment in offspring toxin level, albeit at some cost to mothers. Whether mothers adjust offspring toxin levels in response to variation in predation risk is, however, unknown, but is likely to be important when assessing the response of chemically defended species to the recent and pervasive changes in the global predator landscape, driven by the spread of invasive species. Using the chemically defended two-spot ladybird, Adalia bipunctata, we investigated reproductive investment, including egg toxin level, under conditions that varied in the degree of simulated offspring predation risk from larval harlequin ladybirds, Harmonia axyridis. H. axyridis is a highly voracious alien invasive species in the UK and a significant intraguild predator of A. bipunctata. Females laid fewer, larger egg clusters, under conditions of simulated predation risk (P+) than when predator cues were absent (P-), but there was no difference in toxin level between the two treatments. Among P- females, when mean cluster size increased there were concomitant increases in both the mass and toxin concentration of eggs, however when P+ females increased cluster size there was no corresponding increase in egg toxin level. We conclude that, in the face of offspring predation risk, females either withheld toxins or were physiologically constrained, leading to a trade-off between cluster size and egg toxin level. Our results provide the first demonstration that the risk of offspring predation by a novel invasive predator can influence maternal investment in toxins within their offspring.S.C. Paul was funded by a Natural Environment Research Council PhD studentship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. JK Pell Consulting is the trading name of author J.K. Pell, who is a self employed science consultant (sole trader) in UK; this author contributed to study design and interpretation, decision to publish and preparation of the manuscript. The specific roles of the authors are articulated in the ‘author contributions’ section

    Effects of Low Intensity Focused Ultrasound on Liposomes Containing Channel proteins.

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    The ability to reversibly and non-invasively modulate region-specific brain activity in vivo suggests Low Intensity Focused Ultrasound (LIFU) as potential therapeutics for neurological dysfunctions such as epilepsy and Parkinson's disease. While in vivo studies provide evidence of the bioeffects of LIFU on neuronal activity, they merely hint at potential mechanisms but do not fully explain how this technology achieves these effects. One potential hypothesis is that LIFU produces local membrane depolarization by mechanically perturbing the neuronal cell membrane, or activating channels or other proteins embedded in the membrane. Proteins that sense mechanical perturbations of the membrane, such as those gated by membrane tension, are prime candidates for activating in response to LIFU and thus leading to the neurological responses that have been measured. Here we use the bacterial mechanosensitive channel MscL, which has been purified and reconstituted in liposomes, to determine how LIFU may affect the activation of this membrane-tension gated channel. Two bacterial voltage-gated channels, KvAP and NaK2K F92A channels were also studied. Surprisingly, the results suggest that ultrasound modulation and membrane perturbation does not induce channel gating, but rather induces pore formation at the membrane protein-lipid interface. However, in vesicles with high MscL mechanosensitive channel concentrations, apparent decreases in pore formation are observed, suggesting that this membrane-tension-sensitive protein may serve to increase the elasticity of the membrane, presumably because of expansion of the channel in the plane of the membrane independent of channel gating

    Accuracy of a video odometry system for trains

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    Reliable Data Systems is developing a video-based odometry system that enables trains to measure velocities and distances travelled without the need for trackside infrastructure. A camera is fixed in the cab, taking images of the track immediately ahead, at rates in the range 25–50 frames per second. The images in successive frames are ‘unwarped’ to provide a plan view of the track and then matched, to produce an ‘optical flow’ that measures the distance travelled. The Study Group was asked to investigate ways of putting bounds on the accuracy of such a system, and to suggest any improvements that might be made. The work performed in the week followed three strands: (a) an understanding of how deviations from the camera’s calibrated position lead to errors in the train’s calculated position and velocity; (b) development of models for the train suspension, designed to place bounds on these deviations; and (c) the performance of the associated image processing algorithms

    Traffic-Related Air Pollution and All-Cause Mortality during Tuberculosis Treatment in California.

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    BackgroundAmbient air pollution and tuberculosis (TB) have an impact on public health worldwide, yet associations between the two remain uncertain.ObjectiveWe determined the impact of residential traffic on mortality during treatment of active TB.MethodsFrom 2000-2012, we enrolled 32,875 patients in California with active TB and followed them throughout treatment. We obtained patient data from the California Tuberculosis Registry and calculated traffic volumes and traffic densities in 100- to 400-m radius buffers around residential addresses. We used Cox models to determine mortality hazard ratios, controlling for demographic, socioeconomic, and clinical potential confounders. We categorized traffic exposures as quintiles and determined trends using Wald tests.ResultsParticipants contributed 22,576 person-years at risk. There were 2,305 deaths during treatment for a crude mortality rate of 1,021 deaths per 10,000 person-years. Traffic volumes and traffic densities in all buffers around patient residences were associated with increased mortality during TB treatment, although the findings were not statistically significant in all buffers. As the buffer size decreased, fifth-quintile mortality hazards increased, and trends across quintiles of traffic exposure became more statistically significant. Increasing quintiles of nearest-road traffic volumes in the 100-m buffer were associated with 3%, 14%, 19%, and 28% increased risk of death during TB treatment [first quintile, referent; second quintile hazard ratio (HR)=1.03 [95% confidence interval (CI): 0.86, 1.25]; third quintile HR=1.14 (95% CI: 0.95, 1.37); fourth quintile HR=1.19 (95% CI: 0.99, 1.43); fifth quintile HR=1.28 (95% CI: 1.07, 1.53), respectively; p-trend=0.002].ConclusionsResidential proximity to road traffic volumes and traffic density were associated with increased all-cause mortality in patients undergoing treatment for active tuberculosis even after adjusting for multiple demographic, socioeconomic, and clinical factors, suggesting that TB patients are susceptible to the adverse health effects of traffic-related air pollution. https://doi.org/10.1289/EHP1699

    An agonist of the MscL channel affects multiple bacterial species and increases membrane permeability and potency of common antibiotics

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    The bacterial MscL channel normally functions as an emergency release valve discharging cytoplasmic solutes upon osmotic stress. The channel opens and passes molecules up to 30 Å and its pore is the largest of any gated channel. Opening the MscL pore inappropriately is detrimental to the bacterial cell, suggesting MscL as a potential novel drug target. A small‐molecule compound, 011A, has been shown to increase sensitivity of the Escherichia coli MscL channel, slow growth, and even decrease viability of quiescent cultures. The mscL gene is highly conserved and found in the vast majority of bacterial species, including pathogens. Here, we test the hypothesis that 011A can influence the growth and viability of other bacterial species, specifically Staphylococcus aureus and Mycobacterium smegmatis, in a MscL‐dependent manner. Furthermore, we demonstrate that the 011A compound can increase potency of other antibiotics, presumably by permeabilizing the membrane and allowing easier access of the antibiotic into the cytoplasm. Thus, MscL activators have potential as novel broad‐spectrum antibiotics or adjuvants that work with antibiotics to selectively allow passage across bacterial membranes

    An agonist of the MscL channel affects multiple bacterial species and increases membrane permeability and potency of common antibiotics

    Get PDF
    The bacterial MscL channel normally functions as an emergency release valve discharging cytoplasmic solutes upon osmotic stress. The channel opens and passes molecules up to 30 Å and its pore is the largest of any gated channel. Opening the MscL pore inappropriately is detrimental to the bacterial cell, suggesting MscL as a potential novel drug target. A small‐molecule compound, 011A, has been shown to increase sensitivity of the Escherichia coli MscL channel, slow growth, and even decrease viability of quiescent cultures. The mscL gene is highly conserved and found in the vast majority of bacterial species, including pathogens. Here, we test the hypothesis that 011A can influence the growth and viability of other bacterial species, specifically Staphylococcus aureus and Mycobacterium smegmatis, in a MscL‐dependent manner. Furthermore, we demonstrate that the 011A compound can increase potency of other antibiotics, presumably by permeabilizing the membrane and allowing easier access of the antibiotic into the cytoplasm. Thus, MscL activators have potential as novel broad‐spectrum antibiotics or adjuvants that work with antibiotics to selectively allow passage across bacterial membranes

    Direct Measurement of Perchlorate Exposure Biomarkers in a Highly Exposed Population: A Pilot Study

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    Exposure to perchlorate is ubiquitous in the United States and has been found to be widespread in food and drinking water. People living in the lower Colorado River region may have perchlorate exposure because of perchlorate in ground water and locally-grown produce. Relatively high doses of perchlorate can inhibit iodine uptake and impair thyroid function, and thus could impair neurological development in utero. We examined human exposures to perchlorate in the Imperial Valley among individuals consuming locally grown produce and compared perchlorate exposure doses to state and federal reference doses. We collected 24-hour urine specimen from a convenience sample of 31 individuals and measured urinary excretion rates of perchlorate, thiocyanate, nitrate, and iodide. In addition, drinking water and local produce were also sampled for perchlorate. All but two of the water samples tested negative for perchlorate. Perchlorate levels in 79 produce samples ranged from non-detect to 1816 ppb. Estimated perchlorate doses ranged from 0.02 to 0.51 ”g/kg of body weight/day. Perchlorate dose increased with the number of servings of dairy products consumed and with estimated perchlorate levels in produce consumed. The geometric mean perchlorate dose was 70% higher than for the NHANES reference population. Our sample of 31 Imperial Valley residents had higher perchlorate dose levels compared with national reference ranges. Although none of our exposure estimates exceeded the U. S. EPA reference dose, three participants exceeded the acceptable daily dose as defined by bench mark dose methods used by the California Office of Environmental Health Hazard Assessment

    Membrane-protein interactions in mechanosensitive channels

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    In this paper, we examine the mechanical role of the lipid bilayer in ion channel conformation and function with specific reference to the case of the mechanosensitive channel of large conductance (MscL). In a recent paper (Wiggins and Phillips, 2004), we argued that mechanotransduction very naturally arises from lipid-protein interactions by invoking a simple analytic model of the MscL channel and the surrounding lipid bilayer. In this paper, we focus on improving and expanding this analytic framework for studying lipid-protein interactions with special attention to MscL. Our goal is to generate simple scaling relations which can be used to provide qualitative understanding of the role of membrane mechanics in protein function and to quantitatively interpret experimental results. For the MscL channel, we find that the free energies induced by lipid-protein interaction are of the same order as the free energy differences between conductance states measured by Sukharev et al. (1999). We therefore conclude that the mechanics of the bilayer plays an essential role in determining the conformation and function of the channel. Finally, we compare the predictions of our model to experimental results from the recent investigations of the MscL channel by Perozo et al. (2002), Powl et al. (2003), Yoshimura et al. (2004), and others and suggest a suite of new experiments

    Cryo-EM Structure of Mechanosensitive Channel YnaI Using SMA2000: Challenges and Opportunities

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    Mechanosensitive channels respond to mechanical forces exerted on the cell membrane and play vital roles in regulating the chemical equilibrium within cells and their environment. Highresolution structural information is required to understand the gating mechanisms of mechanosensitive channels. Protein-lipid interactions are essential for the structural and functional integrity of mechanosensitive channels, but detergents cannot maintain the crucial native lipid environment for purified mechanosensitive channels. Recently, detergent-free systems have emerged as alternatives for membrane protein structural biology. This report shows that while membrane-active polymer, SMA2000, could retain some native cell membrane lipids on the transmembrane domain of the mechanosensitive-like YnaI channel, the complete structure of the transmembrane domain of YnaI was not resolved. This reveals a significant limitation of SMA2000 or similar membrane-active copolymers. This limitation may come from the heterogeneity of the polymers and nonspecific interactions between the polymers and the relatively large hydrophobic pockets within the transmembrane domain of YnaI. However, this limitation offers development opportunities for detergent-free technology for challenging membrane proteins
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