181 research outputs found

    The triple-mode pulsating variable V823 Cas

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    Based on extended multicolour CCD photometry of the triple-mode radial pulsator V823 Cas we studied the properties of the coupling frequencies invoked by nonlinear processes. Our results support that a resonance connection as suggested by Antonello & Aikawa (1998) affects the mode coupling behaviour. The P1/P0 period ratio of V823 Cas has an "out of range" value if compared with the period ratios of the known double mode pulsators, while the P2/P1 period ratio is normal. The periods and period ratios cannot be consistently interpret without conflict with pulsation and/or evolution models. We attempt to interpret this failure by the suggestion that at present, the periods of V823 Cas are in a transient, resonance affected state, thus do not reflect the true parameters of the object. The anomalous period change behaviour of the fundamental and second overtone modes supports this idea. We have also raised the possibility that a f0 + f2 = 2f1 resonance may act in triple mode pulsators.Comment: 10 pages, 7 figures, 5 tables. Accepted for publication in Astronomy and Astrophysic

    Boosted coupling of ATP hydrolysis to substrate transport upon cooperative estradiol-17-beta-D-glucuronide binding in a Drosophila ATP binding cassette type-C transporter

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    ATP binding cassette type-C (ABCC) transporters move molecules across cell membranes upon hydrolysis of ATP; however, their coupling of ATP hydrolysis to substrate transport remains elusive. Drosophila multidrug resistance-associated protein (DMRP) is the functional ortholog of human long ABCC transporters, with similar substrate and inhibitor specificity, but higher activity. Exploiting its high activity, we kinetically dissected the catalytic mechanism of DMRP by using E2-d-glucuronide (E2G), the physiologic substrate of human ABCC. We examined the DMRP-mediated interdependence of ATP and E2G in biochemical assays. We observed E2G-dependent ATPase activity to be biphasic at subsaturating ATP concentrations, which implies at least 2 E2G binding sites on DMRP. Furthermore, transport measurements indicated strong nonreciprocal cooperativity between ATP and E2G. In addition to confirming these findings, our kinetic modeling with the Complex Pathway Simulator indicated a 10-fold decrease in the E2G-mediated activation of ATP hydrolysis upon saturation of the second E2G binding site. Surprisingly, the binding of the second E2G allowed for substrate transport with a constant rate, which tightly coupled ATP hydrolysis to transport. In summary, we show that the second E2G binding-similar to human ABCC2-allosterically stimulates transport activity of DMRP. Our data suggest that this is achieved by a significant increase in the coupling of ATP hydrolysis to transport.-Karasik, A., Ledwitch, K. V., Aranyi, T., Varadi, A., Roberts, A., Szeri, F. Boosted coupling of ATP hydrolysis to substrate transport upon cooperative estradiol-17-beta-D-glucuronide binding in a Drosophila ATP binding cassette type-C transporter

    Search for high-amplitude Delta Scuti and RR Lyrae stars in Sloan Digital Sky Survey Stripe 82 using principal component analysis

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    We propose a robust principal component analysis (PCA) framework for the exploitation of multi-band photometric measurements in large surveys. Period search results are improved using the time series of the first principal component due to its optimized signal-to-noise ratio.The presence of correlated excess variations in the multivariate time series enables the detection of weaker variability. Furthermore, the direction of the largest variance differs for certain types of variable stars. This can be used as an efficient attribute for classification. The application of the method to a subsample of Sloan Digital Sky Survey Stripe 82 data yielded 132 high-amplitude Delta Scuti variables. We found also 129 new RR Lyrae variables, complementary to the catalogue of Sesar et al., 2010, extending the halo area mapped by Stripe 82 RR Lyrae stars towards the Galactic bulge. The sample comprises also 25 multiperiodic or Blazhko RR Lyrae stars.Comment: 23 pages, 17 figure

    Two small, cysteine-rich and cationic antifungal proteins from Penicillium chrysogenum: A comparative study of PAF and PAFB

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    The filamentous fungus Penicillium chrysogenum Q176 secretes the antimicrobial proteins (AMPs) PAF and PAFB, which share a compact disulfide-bond mediated, β-fold structure rendering them highly stable. These two AMPs effectively inhibit the growth of human pathogenic fungi in micromolar concentrations and exhibit antiviral potential without causing cytotoxic effects on mammalian cells in vitro and in vivo. The antifungal mechanism of action of both AMPs is closely linked to - but not solely dependent on - the lipid composition of the fungal cell membrane and requires a strictly regulated protein uptake into the cell, indicating that PAF and PAFB are not canonical membrane active proteins. Variations in their antifungal spectrum and their killing dynamics point towards a divergent mode of action related to their physicochemical properties and surface charge distribution. In this review, we relate characteristic features of PAF and PAFB to the current knowledge about other AMPs of different sources. In addition, we present original data that have never been published before to substantiate our assumptions and provide evidences that help to explain and understand better the mechanistic function of PAF and PAFB. Finally, we underline the promising potential of PAF and PAFB as future antifungal therapeutics

    In vitro transport of methotrexate by Drosophila Multidrug Resistance-associated Protein

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    Methotrexate (MTX) is a widely used chemotherapeutic agent, immune suppressant and antimalarial drug. It is a substrate of several human ABC proteins that confer multidrug resistance to cancer cells and determine compartmentalization of a wide range of physiological metabolites and endo or xenobiotics, by their primary active transport across biological membranes. The substrate specificity and tissue distribution of these promiscuous human ABC transporters show a high degree of redundancy, providing robustness to these key physiological and pharmacological processes, such as the elimination of toxins, e.g. methotrexate from the body. A similar network of proteins capable of transporting methotrexate has been recently suggested to exist in Drosophila melanogaster. One of the key players of this putative network is Drosophila Multidrug-resistance Associated Protein (DMRP). DMRP has been shown to be a highly active and promiscuous ABC transporter, capable of transporting various organic anions. Here we provide the first direct evidence that DMRP, expressed alone in a heterologous system lacking other, potentially functionally overlapping D. melanogaster organic anion transporters, is indeed able to transport methotrexate. Our in vitro results support the hypothesized but debated role of DMRP in in vivo methotrexate excretion. © 2018 Karasik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
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