17 research outputs found

    The Physical Conditions in Starbursts Derived from Bayesian Fitting of Mid-IR SEDS: 30 Doradus as a Template

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    To understand and interpret the observed Spectral Energy Distributions (SEDs) of starbursts, theoretical or semi-empirical SED models are necessary. Yet, while they are well-founded in theory, independent verification and calibration of these models, including the exploration of possible degeneracies between their parameters, are rarely made. As a consequence, a robust fitting method that leads to unique and reproducible results has been lacking. Here we introduce a novel approach based on Bayesian analysis to fit the Spitzer-IRS spectra of starbursts using the SED models proposed by Groves et al. (2008). We demonstrate its capabilities and verify the agreement between the derived best fit parameters and actual physical conditions by modelling the nearby, well-studied, giant HII region 30 Dor in the LMC. The derived physical parameters, such as cluster mass, cluster age, ISM pressure and covering fraction of photodissociation regions, are representative of the 30 Dor region. The inclusion of the emission lines in the modelling is crucial to break degeneracies. We investigate the limitations and uncertainties by modelling sub-regions, which are dominated by single components, within 30 Dor. A remarkable result for 30 Doradus in particular is a considerable contribution to its mid-infrared spectrum from hot ({\simeq} 300K) dust. The demonstrated success of our approach will allow us to derive the physical conditions in more distant, spatially unresolved starbursts.Comment: 17 pages, 10 figures. Accepted por publication in the Astrophysical Journa

    Mesoscopic model for DNA G-quadruplex unfolding

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    [EN] Genomes contain rare guanine-rich sequences capable of assembling into four-stranded helical structures, termed G-quadruplexes, with potential roles in gene regulation and chromosome stability. Their mechanical unfolding has only been reported to date by all-atom simulations, which cannot dissect the major physical interactions responsible for their cohesion. Here, we propose a mesoscopic model to describe both the mechanical and thermal stability of DNA G-quadruplexes, where each nucleotide of the structure, as well as each central cation located at the inner channel, is mapped onto a single bead. In this framework we are able to simulate loading rates similar to the experimental ones, which are not reachable in simulations with atomistic resolution. In this regard, we present single-molecule force-induced unfolding experiments by a high-resolution optical tweezers on a DNA telomeric sequence capable of adopting a G-quadruplex conformation. Fitting the parameters of the model to the experiments we find a correct prediction of the rupture-force kinetics and a good agreement with previous near equilibrium measurements. Since G-quadruplex unfolding dynamics is halfway in complexity between secondary nucleic acids and tertiary protein structures, our model entails a nanoscale paradigm for non-equilibrium processes in the cell.Work supported by the Spanish Ministry of Economy and Competitiveness (MINECO), grant No. FIS2014-55867, co-financed by FEDER funds. We also thank the support of the Aragon Government and Fondo Social Europeo to FENOL group. Work in J.R.A.-G. laboratory was supported by a grant from MINECO, No. MAT2015-71806-R).Bergues-Pupo, A.; Gutiérrez, I.; Arias-Gonzalez, JR.; Falo, F.; Fiasconaro, A. (2017). Mesoscopic model for DNA G-quadruplex unfolding. Scientific Reports. 7:1-13. https://doi.org/10.1038/s41598-017-10849-2S1137Arias-Gonzalez, J. R. Single-molecule portrait of DNA and RNA double helices. Integr. Biol. 6, 904 (2014).Burge, S., Parkinson, G. N., Hazel, P., Todd, A. K. & Neidle, S. Quadruplex DNA: sequence, topology and structure. Nucleic Acids Res. 34, 5402 (2006).Lam, E. Y., Beraldi, D., Tannahill, D. & Balasubramanian, S. G-quadruplex structures are stable and detectable in human genomic DNA. Nat. Commun. 4, 1796 (2013).Siddiqui-Jain, A., Grand, C. L., Bearss, D. J. & Hurley, L. H. Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription. Proc. Natl. Acad. Sci. USA 99, 11593 (2002).Endoh, T. & Sugimoto, N. Mechanical insights into ribosomal progression overcoming RNA G-quadruplex from periodical translation suppression in cells. Sci. Rep. 6, 1 (2016).Hänsel-Hertsch, R., Di Antonio, M. & Balasubramanian, S. DNA G-quadruplexes in the human genome: detection, functions and therapeutic potential. Nat. Rev. Mol. Cell Biol. 18, 279 (2017).de Messieres, M., Chang, J. C., Brawn-Cinani, B. & La Porta, A. Single-molecule study of G-quadruplex disruption using dynamic force spectroscopy. Phys. Rev. Lett. 109, 058101 (2012).Koirala, D. et al. A single-molecule platform for investigation of interactions between G-quadruplexes and small-molecule ligands. Nat. Chem. 3, 782 (2011).Long, X. et al. Mechanical unfolding of human telomere G-quadruplex DNA probed by integrated fluorescence and magnetic tweezers spectroscopy. Nucleic Acids Res. 41, 2746 (2013).Ghimire, C. et al. Direct Quantification of Loop Interaction and pi-pi Stacking for G-Quadruplex Stability at the Submolecular Level. J. Am. Chem. Soc. 136, 15544 (2014).Garavís, M. et al. Mechanical Unfolding of Long Human Telomeric RNA (TERRA). Chem. Commun. 49, 6397 (2013).Fonseca Guerra, C., Zijlstra, H., Paragi, G. & Bickelhaupt, F. M. Telomere structure and stability: covalency in hydrogen bonds, not resonance assistance, causes cooperativity in guanine quartets. Chemistry-A European Journal 17, 12612 (2011).Yurenko, Y. P., Novotn, J., Sklen, V. & Marek, R. Exploring non-covalent interactions in guanine-and xanthine-based model DNA quadruplex structures: a comprehensive quantum chemical approach. Phys. Chem. Chem. Phys. 16, 2072 (2014).Poudel, L. et al. Implication of the solvent effect, metal ions and topology in the electronic structure and hydrogen bonding of human telomeric G-quadruplex DNA. Phys. Chem. Chem. Phys. 18, 21573 (2016).Li, M. H., Luo, Q., Xue, X. G. & Li, Z. S. Toward a full structural characterization of G-quadruplex DNA in aqueous solution: Molecular dynamics simulations of four G-quadruplex molecules. J. Mol. Struct-Theochem. 952, 96 (2010).Islam, B. et al. Conformational dynamics of the human propeller telomeric DNA quadruplex on a microsecond time scale. Nucleic Acids Res. 41, 2723 (2013).Stadlbauer, P., Krepl, M., Cheatham, T. E., Koca, J. & Sponer, J. Structural dynamics of possible late-stage intermediates in folding of quadruplex DNA studied by molecular simulations. Nucleic Acids Res. 41, 7128 (2013).Li, H., Cao, E. & Gisler, T. Force-induced unfolding of human telomeric G-quadruplex: a steered molecular dynamics simulation study. Biochem. Bioph. Res. Co. 379, 70 (2009).Yang, C., Jang, S. & Pak, Y. Multiple stepwise pattern for potential of mean force in unfolding the thrombin binding aptamer in complex with Sr2+. J. Chem. Phys. 135, 225104 (2011).Bergues-Pupo, A. E., Arias-Gonzalez, J. R., Morón, M. C., Fiasconaro, A. & Falo, F. Role of the central cations in the mechanical unfolding of DNA and RNA G-quadruplexes. Nucleic Acids Res. 43, 7638 (2015).Linak, M. C., Tourdot, R. & Dorfman, K. D. Moving beyond Watson-Crick models of coarse grained DNA dynamics. J. Chem Phys. 135, 205102 (2011).Rebi, M., Mocci, F., Laaksonen, A. & Ulin, J. Multiscale simulations of human telomeric G-quadruplex DNA. J. Phys. Chem. B 119, 105 (2014).Stadlbauer, P. et al. 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    D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile

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    Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients

    Spitzer Mid-Infrared Spectra of Selected Galaxy Cluster Cooling Flows

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    We present sparse spectral maps of eight massive galaxy cluster cooling flows, using the Infrared Spectrograph of the Spitzer Space Telescope. Our targets are located at distances from z = 0.05 to 0.29. The total LMIR in these objects, integrated from 12 to 25 mum, ranges between 1041 and 1043 erg s-1. In the mid-infrared (MIR), two of the targets are point sources, while we have detected extended emission in the other six. The estimated cooling rates from X-ray observations range from 10 to 200 MSun/yr. Their MIR spectra exhibit very different morphologies, from classic starbursts to Seyfert nuclei. Vibrationally excited molecular hydrogen is detected in all of our sources, with medium to strong emission lines in most of the spectra. Abell 1068, Abell 1835, and Hydra A display the hallmarks of starburst galaxies: a rising red continuum as well as prominent emission from large aromatic molecules and low-ionization atomic lines, and no high-ionization atomic line emission. Abell 1068 closely resembles a Seyfert 2 galaxy with a nuclear starburst. Three more of the objects, Abell 1795, Abell 478, and Abell 2597, have a common but unusual morphology, characterized by a flat continuum, weak aromatic molecular emission, and strong molecular hydrogen and low-ionization atomic line emission. PKS 0745-19 shares the suite of strong H2 lines and has a shallow continuum rise toward the red. The MIR spectrum of MS0735.6+7421 is entirely different from the others, dominated by H2 lines with a continuum rise toward the blue. We will use our results to improve estimates of the star formation rate in the central dominant galaxies and compare this to the gas deposition rate

    "Dark Skies, Bright Kids" -- Astronomy Education and Outreach in Rural Virginia

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    In the hills of central Virginia, the extraordinarily dark nighttime skies of southern Albemarle County provide a natural outdoor classroom for local science education. Until recently, this rural area lacked the financial and educational support to take full advantage of this rare and valuable natural resource. With funds provided by the NSF, a team of volunteers from the University of Virginia introduced a new program this fall called "Dark Skies - Bright Kids," which promotes science education at the elementary school level through a wide range of activities. The program volunteers (comprising undergraduate and graduate students, postdocs, and faculty) have sought to develop a coherent schedule of fun and educational activities throughout the semester, with emphases on hands-on learning and critical thinking. For example, students learn about the constellations by making star-wheels, about rocketry by building and launching rockets, and about comets by assembling miniature analogs. Additional activities include stories about the scientific and cultural history of astronomy, visits by professional astronomers and popular book authors, and astronomy-themed exercises in art, music, and physical education. These projects are designed to make astronomy, and by extension all science, accessible and appealing to each student. Family involvement is important in any educational environment, particularly at the elementary school level. To include the students' families and the larger community in "Dark Skies," we hold weekly telescope observing sessions at the school. Here, all interested parties can come together to hear what the students are learning and view astronomical objects through a small telescope. We hope that this well-received program will soon expand to other disadvantaged schools in the area. The "Dark Skies" team is proud and excited to have an impact on the scientific literacy of the students in these starry-skied communities

    "Dark Skies, Bright Kids" -- Astronomy Education and Outreach in Rural Virginia

    No full text
    In the hills of central Virginia, the extraordinarily dark nighttime skies of southern Albemarle County provide a natural outdoor classroom for local science education. Until recently, this rural area lacked the financial and educational support to take full advantage of this rare and valuable natural resource. With funds provided by the NSF, a team of volunteers from the University of Virginia introduced a new program this fall called "Dark Skies - Bright Kids," which promotes science education at the elementary school level through a wide range of activities. The program volunteers (comprising undergraduate and graduate students, postdocs, and faculty) have sought to develop a coherent schedule of fun and educational activities throughout the semester, with emphases on hands-on learning and critical thinking. For example, students learn about the constellations by making star-wheels, about rocketry by building and launching rockets, and about comets by assembling miniature analogs. Additional activities include stories about the scientific and cultural history of astronomy, visits by professional astronomers and popular book authors, and astronomy-themed exercises in art, music, and physical education. These projects are designed to make astronomy, and by extension all science, accessible and appealing to each student. Family involvement is important in any educational environment, particularly at the elementary school level. To include the students' families and the larger community in "Dark Skies," we hold weekly telescope observing sessions at the school. Here, all interested parties can come together to hear what the students are learning and view astronomical objects through a small telescope. We hope that this well-received program will soon expand to other disadvantaged schools in the area. The "Dark Skies" team is proud and excited to have an impact on the scientific literacy of the students in these starry-skied communities
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