853 research outputs found

    Aldosterone upregulates transient receptor potential melastatin 7 (TRPM7)

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    Transient receptor potential melastatin 7 (TRPM7) is a ubiquitously expressed Mg2+-permeable ion channel fused to a C-terminal α-kinase domain. Recently, aldosterone was shown to increase intracellular Mg2+ levels and alter inflammatory signaling in TRPM7-expressing HEK293 cells. This study was undertaken to assess whether these effects were related to an aldosterone-mediated increase of TRPM7 current and/or plasma membrane localization. Using HEK293 cells stably expressing WT-TRPM7, we found that 18-h application of aldosterone significantly increased TRPM7 current and TRPM7 plasma membrane protein expression by 48% and 34%, respectively. The aldosterone-mediated increase of TRPM7 current was inhibited by eplerenone, a mineralocorticoid receptor (MR) blocker, and GSK-650394, an inhibitor of the serum- and glucocorticoid-regulated kinase 1 (SGK1). SGK1 blockade also prevented the aldosterone-induced increase of TRPM7 plasma membrane protein. It was further determined that K1648R-TRPM7, the phosphotransferase-inactive TRPM7 mutant, was unresponsive to aldosterone. Therefore, chronic aldosterone treatment increases the plasma membrane expression of TRPM7, which is associated with an increase of TRPM7 current. This process occurs via an MR-dependent, genomic signaling cascade involving SGK1 and a functioning TRPM7 α-kinase domain. We suggest that this mechanism may be of general relevance when interpreting the effects of aldosterone because the MR receptor is found in multiple tissues, and TRPM7 and SGK1 are ubiquitously expressed

    A Symplectic Integrator for Hill's Equations

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    Hill's equations are an approximation that is useful in a number of areas of astrophysics including planetary rings and planetesimal disks. We derive a symplectic method for integrating Hill's equations based on a generalized leapfrog. This method is implemented in the parallel N-body code, PKDGRAV and tested on some simple orbits. The method demonstrates a lack of secular changes in orbital elements, making it a very useful technique for integrating Hill's equations over many dynamical times. Furthermore, the method allows for efficient collision searching using linear extrapolation of particle positions.Comment: 15 pages, 2 figures; minor revisions; accepted for publication in the Astronomical Journa

    Sustaining Economic Exploitation of Complex Ecosystems in Computational Models of Coupled Human-Natural Networks

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    Understanding ecological complexity has stymied scientists for decades. Recent elucidation of the famously coined "devious strategies for stability in enduring natural systems" has opened up a new field of computational analyses of complex ecological networks where the nonlinear dynamics of many interacting species can be more realistically mod-eled and understood. Here, we describe the first extension of this field to include coupled human-natural systems. This extension elucidates new strategies for sustaining extraction of biomass (e.g., fish, forests, fiber) from ecosystems that account for ecological complexity and can pursue multiple goals such as maximizing economic profit, employment and carbon sequestration by ecosystems. Our more realistic modeling of ecosystems helps explain why simpler "maxi-mum sustainable yield" bioeconomic models underpinning much natural resource extraction policy leads to less profit, biomass, and biodiversity than predicted by those simple models. Current research directions of this integrated natu-ral and social science include applying artificial intelligence, cloud computing, and multiplayer online games

    Ramanujan sums for signal processing of low frequency noise

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    An aperiodic (low frequency) spectrum may originate from the error term in the mean value of an arithmetical function such as M\"obius function or Mangoldt function, which are coding sequences for prime numbers. In the discrete Fourier transform the analyzing wave is periodic and not well suited to represent the low frequency regime. In place we introduce a new signal processing tool based on the Ramanujan sums c_q(n), well adapted to the analysis of arithmetical sequences with many resonances p/q. The sums are quasi-periodic versus the time n of the resonance and aperiodic versus the order q of the resonance. New results arise from the use of this Ramanujan-Fourier transform (RFT) in the context of arithmetical and experimental signalsComment: 11 pages in IOP style, 14 figures, 2 tables, 16 reference

    Dimerization of the voltage-sensing phosphatase controls its voltage-sensing and catalytic activity.

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    Multimerization is a key characteristic of most voltage-sensing proteins. The main exception was thought to be the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP). In this study, we show that multimerization is also critical for Ci-VSP function. Using coimmunoprecipitation and single-molecule pull-down, we find that Ci-VSP stoichiometry is flexible. It exists as both monomers and dimers, with dimers favored at higher concentrations. We show strong dimerization via the voltage-sensing domain (VSD) and weak dimerization via the phosphatase domain. Using voltage-clamp fluorometry, we also find that VSDs cooperate to lower the voltage dependence of activation, thus favoring the activation of Ci-VSP. Finally, using activity assays, we find that dimerization alters Ci-VSP substrate specificity such that only dimeric Ci-VSP is able to dephosphorylate the 3-phosphate from PI(3,4,5)P3 or PI(3,4)P2 Our results indicate that dimerization plays a significant role in Ci-VSP function

    A way to increase the bit ratein ionospheric radio links

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    The aim of this paper is to present a high data rate transmission system through the ionospheric channel in the HF-band (3-30 MHz). The applications expected in this study are image transmitting and real-time videoconferencing. Very high rates are required compared to the standard modems. Therefore, an array processing is performed with a set of antennas whose spatial response differs from one another arranged in a circular array or in a collocated sensor. Synchronization (Zero Crossing Detector) and source separation (LMS algorithm) resort to classical well-tested techniques involving training sequences. Experimental results are presented for both antenna configurations. These techniques improve data rate, reaching 20 kbits/s within the 6 kHz bandwidth (QAM 64) without coding or interleaving

    Olfactory ensheathing glia are required for embryonic olfactory axon targeting and the migration of gonadotropin-releasing hormone neurons.

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    Kallmann's syndrome is caused by the failure of olfactory axons and gonadotropin-releasing hormone (GnRH) neurons to enter the embryonic forebrain, resulting in anosmia and sterility. Sox10 mutations have been associated with Kallmann's syndrome phenotypes, but their effect on olfactory system development is unknown. We recently showed that Sox10 is expressed by neural crest-derived olfactory ensheathing cells (OECs). Here, we demonstrate that in homozygous Sox10(lacZ/lacZ) mouse embryos, OEC differentiation is disrupted; olfactory axons accumulate in the ventromedial olfactory nerve layer and fewer olfactory receptor neurons express the maturation marker OMP (most likely owing to the failure of axonal targeting). Furthermore, GnRH neurons clump together in the periphery and a smaller proportion enters the forebrain. Our data suggest that human Sox10 mutations cause Kallmann's syndrome by disrupting the differentiation of OECs, which promote embryonic olfactory axon targeting and hence olfactory receptor neuron maturation, and GnRH neuron migration to the forebrain.This work was supported by the Wellcome Trust [grant 091555 to C.V.H.B. and P.B.], a Griffith University Encouragement Research grant to J.A.S., and Deutsche Forschungsgemeinschaft [grant We1326/9 to M.W.].This is the final version of the article. It was first available from The Company of Biologists via http://dx.doi.org/10.1242/bio.2013524

    A multiwavelength study of the remnant of nova GK Persei

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    We present new observations of the nebular remnant of the old nova GK Persei 1901, in the optical using the 2m HCT and at low radio frequencies using the GMRT. The evolution of the nova remnant indicates shock interaction with the ambient medium, especially in the southwest quadrant. Application of a simple model for the shock and its evolution to determine the time dependence of the radius of the shell in the southwest quadrant indicates that the shell is now expanding into an ambient medium that has a lower density compared to the density of the ambient medium ahead of the shock in 1987.There are indications of a recent interaction of the nova remnant with the ambient medium in the northeast quadrant also. The nova remnant of GK Per is detected at all the observed radio frequencies and is of similar extent as the optical remnant. Putting together our radio observations with VLA archival data on GK Per from 1997, we obtain three interesting results: 1. The spectrum above 1.4 GHz follows a power law with an index -0.7 and below 1.4 GHz follows a power law with an index ~ -0.85. This could be due to the presence of at least two populations of electrons dominating the global emission at different frequencies. 2. We record an annual secular decrease of 2.1% in the flux density of the nova remnant at 1.4 and 4.9 GHz between 1984 and 1997 which has left the spectral index unchanged at -0.7. No such decrease is observed in the flux densities below 1 GHz. 3. We record an increase in the flux density at 0.33 GHz compared to the previous estimate in 1987. We conclude that the remnant of nova GK Per is similar to supernova remnants and in particular, to the young supernova remnant Cas A.Comment: 10 pages; uses A&A style; figures 1, 2 & 6 are in JPEG format. Accepted for publication in Astronomy & Astrophysics. Full paper including Figures 1, 2 & 6 may be downloaded from http://www.iiap.res.in/personnel/gca/gca.htm
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