Photometric and spectroscopic monitoring, radial velocities and evolutionary status of the chromospherically active, close eclipsing binaries ST Centauri and V0775 Centauri
ASTROPHYSICS AND SPACE SCIENCE
Authors: Moriarty, D. J. W.; Liakos, A.; Drinkwater, M. J.; Mohit, A.; Sweet, S. M.; West, J. F.
Abstract
We have combined photometric and spectroscopic observations of two very close eclipsing binary systems, ST Centauri and V775 Centauri, to determine their evolutionary state from calculations of masses and radii and other properties. Spectral types were determined and radial velocities calculated from spectra obtained with the Australian National University's 2.3 m telescope and Wide Field Spectrograph. The spectral type of the ST Cen primary component is F8 IV and the secondary is F8-8.5 IV. The ST Cen mean masses and radii of 1.40 +/- 0.05M circle dot for components 1 and 2 respectively. Our data show that V775 Cen is a close Algol binary system, with a secondary component that has evolved beyond terminal age Main Sequence, has filled its inner critical equipotential surface and is transferring mass to the primary star. The masses and radii of both components of V775 Cen are smaller than those of other Algol binary systems. Although the primary component of V775 Cen is on the Main Sequence, its spectral type is F0/F1 class IV. Both systems displayed episodes of photospheric and chromospheric activity. This was evident in the H alpha lines of ST Cen and the Na I D lines of the components in both systems. Narrow Na I D lines between those of the binary components suggest that circumbinary gas is present.
Sensitized mutagenesis screen in Factor V Leiden mice identifies thrombosis suppressor loci
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Authors: Westrick, Randal J.; Tomberg, Kart; Siebert, Amy E.; Zhu, Guojing; Winn, Mary E.; Dobies, Sarah L.; Manning, Sara L.; Brake, Marisa A.; Cleuren, Audrey C.; Hobbs, Linzi M.; Mishack, Lena M.; Johnston, Alexander J.; Kotnik, Emilee; Siemieniak, David R.; Xu, Jishu; Li, Jun Z.; Saunders, Thomas L.; Ginsburg, David
Abstract
Factor V Leiden (F5(L)) is a common genetic risk factor for venous thromboembolism in humans. We conducted a sensitized N-ethyl-N-nitrosourea (ENU) mutagenesis screen for dominant thrombosuppressor genes based on perinatal lethal thrombosis in mice homozygous for F5(L) (F5(L/L)) and haploinsufficient for tissue factor pathway inhibitor (Tfpi(+/-)). F8 deficiency enhanced the survival of F5(L/L) Tfpi(+/-) mice, demonstrating that F5(L/L) Tfpi(+/-) lethality is genetically suppressible. ENU-mutagenized F5(L/L) males and F5(L/+) Tfpi(+/-) females were crossed to generate 6,729 progeny, with 98 F5(L/L) Tfpi(+/-) offspring surviving until weaning. Sixteen lines, referred to as "modifier of Factor 5 Leiden (MF5L1-16)," exhibited transmission of a putative thrombosuppressor to subsequent generations. Linkage analysis in MF5L6 identified a chromosome 3 locus containing the tissue factor gene (F3). Although no ENU-induced F3 mutation was identified, haploinsufficiency for F3 (F3(+/-)) suppressed F5(L/L) Tfpi(+/)- lethality. Whole-exome sequencing in MF5L12 identified an Actr2 gene point mutation (p.R258G) as the sole candidate. Inheritance of this variant is associated with suppression of F5(L/L) Tfpi(+/-) lethality (P = 1.7 x 10(-6)), suggesting that Actr2(p.R258G) is thrombosuppressive. CRISPR/Cas9 experiments to generate an independent Actr2 knockin/knockout demonstrated that Actr2 haploinsufficiency is lethal, supporting a hypomorphic or gain-of-function mechanism of action for Actr2(p.R258G). Our findings identify F8 and the Tfpi/F3 axis as key regulators in determining thrombosis balance in the setting of F5L and also suggest a role for Actr2 in this process.
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