5,993 research outputs found

    Connexin Specificity of Second Messenger Permeation: Real Numbers At Last

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    Ash plume properties retrieved from infrared images: a forward and inverse modeling approach

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    We present a coupled fluid-dynamic and electromagnetic model for volcanic ash plumes. In a forward approach, the model is able to simulate the plume dynamics from prescribed input flow conditions and generate the corresponding synthetic thermal infrared (TIR) image, allowing a comparison with field-based observations. An inversion procedure is then developed to retrieve ash plume properties from TIR images. The adopted fluid-dynamic model is based on a one-dimensional, stationary description of a self-similar (top-hat) turbulent plume, for which an asymptotic analytical solution is obtained. The electromagnetic emission/absorption model is based on the Schwarzschild's equation and on Mie's theory for disperse particles, assuming that particles are coarser than the radiation wavelength and neglecting scattering. [...] Application of the inversion procedure to an ash plume at Santiaguito volcano (Guatemala) has allowed us to retrieve the main plume input parameters, namely the initial radius b0b_0, velocity U0U_0, temperature T0T_0, gas mass ratio n0n_0, entrainment coefficient kk and their related uncertainty. Moreover, coupling with the electromagnetic model, we have been able to obtain a reliable estimate of the equivalent Sauter diameter dsd_s of the total particle size distribution. The presented method is general and, in principle, can be applied to the spatial distribution of particle concentration and temperature obtained by any fluid-dynamic model, either integral or multidimensional, stationary or time-dependent, single or multiphase. The method discussed here is fast and robust, thus indicating potential for applications to real-time estimation of ash mass flux and particle size distribution, which is crucial for model-based forecasts of the volcanic ash dispersal process.Comment: 41 pages, 13 figures, submitted pape

    HST Photometry for the Halo Stars in the Leo Elliptical NGC 3377

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    We have used the ACS camera on HST to obtain (V,I) photometry for 57,000 red-giant stars in the halo of the Leo elliptical NGC 3377. We use this sample of stars to derive the metallicity distribution function (MDF) for its halo field stars, and comment on its chemical evolution history compared with both larger and smaller E galaxies. Our ACS/WFC field spans a radial range extending from 4 to 18 kpc projected distance from the center of NGC 3377 and thus covers a significant portion of this galaxy's halo. We find that the MDF is broad, reaching a peak at [m/H] ~ -0.6,butcontainingvirtuallynostarsmoremetalpoorthanlog[m/H]=1.5, but containing virtually no stars more metal-poor than log [m/H] = -1.5. It may, in addition, have relatively few stars more metal-rich than [m/H] = -0.3$, although interpretation of the high-metallicity end of the MDF is limited by photometric completeness that affects the detection of the reddest, most metal-rich stars. NGC 3377 appears to have an enrichment history intermediate between those of normal dwarf ellipticals and the much larger giants. As yet, we find no clear evidence that the halo of NGC 3377 contains a significant population of ``young'' (< 3 Gy) stars.Comment: 40 pages, 17 figure

    Minimum requirements for feedback enhanced force sensing

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    The problem of estimating an unknown force driving a linear oscillator is revisited. When using linear measurement, feedback is often cited as a mechanism to enhance bandwidth or sensitivity. We show that as long as the oscillator dynamics are known, there exists a real-time estimation strategy that reproduces the same measurement record as any arbitrary feedback protocol. Consequently some form of nonlinearity is required to gain any advantage beyond estimation alone. This result holds true in both quantum and classical systems, with non-stationary forces and feedback, and in the general case of non-Gaussian and correlated noise. Recently, feedback enhanced incoherent force sensing has been demonstrated [Nat. Nano. \textbf{7}, 509 (2012)], with the enhancement attributed to a feedback induced modification of the mechanical susceptibility. As a proof-of-principle we experimentally reproduce this result through straightforward filtering.Comment: 5 pages + 2 pages of Supplementary Informatio

    Light-emitting diode street lights reduce last-ditch evasive manoeuvres by moths to bat echolocation calls

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    © 2015 The Authors. The light-emitting diode (LED) street light market is expanding globally, and it is important to understand how LED lights affect wildlife populations. We compared evasive flight responses of moths to bat echolocation calls experimentally under LED-lit and -unlit conditions. Significantly, fewer moths performed ‘powerdive’ flight manoeuvres in response to bat calls (feeding buzz sequences from Nyctalus spp.) under an LED street light than in the dark. LED street lights reduce the anti-predator behaviour of moths, shifting the balance in favour of their predators, aerial hawking bats

    Evasion of the toxic effects of oxygen

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    Oxygen is an efficient terminal electron acceptor in respiratory pathways. During aerobic respiration the electron transport chain generates free radical oxygen species as a result of electron leakage; this generation of toxic species is proportional to the oxygen tension (51). In addition, toxic oxygen species (TOS) may be formed exogenously, for example, by chemical processes or through radiation. TOS also result from the oxidative burst of polymorphonuclear leukocytes (PMN). Infection with Helicobacter pylori induces an inflammatory response (gastritis), which leads to an increase in the level of TOS in the gastric mucosa and the gastric juice (4, 24–26, 59). This increase in the level of toxic metabolites is probably the result of the generation of the superoxide anion (O2·− ), a reactive TOS, formed as part of the oxidative burst of PMN and enzymic activities of gastric epithelial cells. There is evidence that H. pylori infection leads to increased production of O2·− via NADPH oxidase in gastric cells, stimulated by lipopolysaccharide as well as xanthine oxidase, another mechanism for the generation of oxygen-derived free radicals (8, 80). In response to increased superoxide anion production in gastric tissue, changes have been detected in the level of expression of human superoxide dismutase (SOD) (12). Human gastric SOD exists as a cytoplasmic copper-zinc-superoxide dismutase (Cu, Zn-SOD) found in gland cells of the gastric body and antral mucosa, and as a manganese-superoxide dismutase (Mn-SOD) within mitochondria (63). An increase in the amount and activity of Mn-SOD has been observed in response to H. pylori infection and gastritis, whereas the amount and activity of the Cu, Zn-SOD remained constant or decreased slightly (39). It has been suggested that the induction of Mn-SOD is in response to increased cytokine production within the inflamed gastric mucosa (39). This situation is reversed following successful treatment of the infection (38). The data suggest that within the gastric environment H. pylori may be exposed to increased levels of TOS. In such an environment it is important for bacterial survival that the impact of such TOS be neutralized

    Ca2+-dependent Inactivation of CaV1.2 Channels Prevents Gd3+ Block: Does Ca2+ Block the Pore of Inactivated Channels?

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    Lanthanide gadolinium (Gd3+) blocks CaV1.2 channels at the selectivity filter. Here we investigated whether Gd3+ block interferes with Ca2+-dependent inactivation, which requires Ca2+ entry through the same site. Using brief pulses to 200 mV that relieve Gd3+ block but not inactivation, we monitored how the proportions of open and open-blocked channels change during inactivation. We found that blocked channels inactivate much less. This is expected for Gd3+ block of the Ca2+ influx that enhances inactivation. However, we also found that the extent of Gd3+ block did not change when inactivation was reduced by abolition of Ca2+/calmodulin interaction, showing that Gd3+ does not block the inactivated channel. Thus, Gd3+ block and inactivation are mutually exclusive, suggesting action at a common site. These observations suggest that inactivation causes a change at the selectivity filter that either hides the Gd3+ site or reduces its affinity, or that Ca2+ occupies the binding site at the selectivity filter in inactivated channels. The latter possibility is supported by previous findings that the EEQE mutation of the selectivity EEEE locus is void of Ca2+-dependent inactivation (Zong Z.Q., J.Y. Zhou, and T. Tanabe. 1994. Biochem. Biophys. Res. Commun. 201:1117–11123), and that Ca2+-inactivated channels conduct Na+ when Ca2+ is removed from the extracellular medium (Babich O., D. Isaev, and R. Shirokov. 2005. J. Physiol. 565:709–717). Based on these results, we propose that inactivation increases affinity of the selectivity filter for Ca2+ so that Ca2+ ion blocks the pore. A minimal model, in which the inactivation “gate” is an increase in affinity of the selectivity filter for permeating ions, successfully simulates the characteristic U-shaped voltage dependence of inactivation in Ca2+

    2-aminoethoxydiphenyl borate directly inhibits channels composed of connexin26 and/or connexin32.

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    ABSTRACT 2-Aminoethoxydiphenyl borate (2-APB), a commonly used blocker of IP 3 -induced calcium ion release and of store-operated channels, inhibits gap junction conductance when applied to cultured cells. The character and pharmacology of this inhibition was explored using 1) hemichannels composed of connexin32 (Cx32) and/or connexin26 (Cx26) purified from native sources and from transfected HeLa cells in which the connexin had a cleavable C-terminal epitope tag and 2) the corresponding junctional channels. Using reconstituted hemichannels in a liposome-based transport-specific fractionation assay (TSF), 2-APB reversibly inhibited homomeric Cx32 and heteromeric Cx26/Cx32 channels from native tissue and their tagged forms from HeLa cells. The IC 50-TSF value of the inhibition was ϳ47M at pH 6.5. 2-APB did not inhibit tagged homomeric Cx26 channels even after tag cleavage (leaving several amino acids at the carboxyl terminus). Protonated 2-APB is the inhibitory agent, but channel sensitivity to 2-APB also increases as pH is lowered. To help define the chemical requirements for inhibition, the effects of four structural analogs of 2-APB were determined. The inhibitory action of 2-APB was shown to be distinct from that of aminosulfonates. 2-APB and its analogs, except phenytoin, inhibited dye-coupling through junctional channels formed by all the tagged channel forms except Cx26, consistent with the TSF studies. However 2-APB significantly inhibited dye coupling between cells expressing untagged Cx26, suggesting that an unmodified C terminus is required for action on Cx26 channels. These results show that protonated 2-APB directly and reversibly inhibits connexin channels composed of Cx26 and/or Cx32 and suggest involvement of the carboxyl-terminal domain

    Pharmacodynamics and Biodistribution of Single-Dose Liposomal Amphotericin B at Different Stages of Experimental Visceral Leishmaniasis.

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    Visceral leishmaniasis is a neglected tropical disease that causes significant morbidity and mortality worldwide. Characterization of the pharmacokinetics and pharmacodynamics of antileishmanial drugs in preclinical models is important for drug development and use. Here we investigated the pharmacodynamics and drug distribution of liposomal amphotericin B (AmBisome) in Leishmania donovani-infected BALB/c mice at three different dose levels and two different time points after infection. We additionally compared drug levels in plasma, liver, and spleen in infected and uninfected BALB/c mice over time. At the highest administered dose of 10 mg/kg AmBisome, >90% parasite inhibition was observed within 2 days after drug administration, consistent with drug distribution from blood to tissue within 24 h and a fast rate of kill. Decreased drug potency was observed in the spleen when AmBisome was administered on day 35 after infection, compared to day 14 after infection. Amphotericin B concentrations and total drug amounts per organ were lower in liver and spleen when AmBisome was administered at the advanced stage of infection and compared to those in uninfected BALB/c mice. However, the magnitude of difference was lower when total drug amounts per organ were estimated. Differences were also noted in drug distribution to L. donovani-infected livers and spleens. Taken together, our data suggest that organ enlargement and other pathophysiological factors cause infection- and organ-specific drug distribution and elimination after administration of single-dose AmBisome to L. donovani-infected mice. Plasma drug levels were not reflective of changes in drug levels in tissues
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