On type Ia supernovae and the formation of single low-mass white dwarfs

There is still considerable debate over the progenitors of type Ia supernovae (SNe Ia). Likewise, it is not agreed how single white dwarfs with masses less than ~0.5 Msun can be formed in the field, even though they are known to exist. We consider whether single low-mass white dwarfs (LMWDs) could have been formed in binary systems where their companions have exploded as a SN Ia. In this model, the observed single LMWDs are the remnants of giant-branch donor stars whose envelopes have been stripped off by the supernova explosion. We investigate the likely remnants of SNe Ia, including the effects of the explosion on the envelope of the donor star. We also use evolutionary arguments to examine alternative formation channels for single LMWDs. In addition, we calculate the expected kinematics of the potential remnants of SNe Ia. SN Ia in systems with giant-branch donor stars can naturally explain the production of single LMWDs. It seems difficult for any other formation mechanism to account for the observations, especially for those single LMWDs with masses less than ~0.4 Msun. Independent of those results, we find that the kinematics of one potentially useful population containing single LMWDs is consistent with our model. Studying remnant white-dwarf kinematics seems to be a promising way to investigate SN Ia progenitors. The existence of single LMWDs appears to constitute evidence for the production of SNe Ia in binary systems with a red-giant donor star. Other single white dwarfs with higher space velocities support a second, probably dominant, population of SN Ia progenitors which contained main-sequence or subgiant donor stars at the time of explosion. The runaway stars LP400-22 and US 708 suggest the possibility of a third formation channnel for some SNe Ia in systems where the donor stars are hot subdwarfs.Comment: Accepted for publication in Astronomy & Astrophysic

CDH12 as a Candidate Gene for Kidney Injury in Posterior Urethral Valve Cases:A Genome-wide Association Study Among Patients with Obstructive Uropathies

Background: Posterior urethral valves (PUVs) and ureteropelvic junction obstruction (UPJO) are congenital obstructive uropathies that may impair kidney development. Objective: To identify genetic variants associated with kidney injury in patients with obstructive uropathy. Design, setting, and participants: We included 487 patients born in 1981 or later who underwent pyeloplasty or valve resection before 18 yr of age in the discovery phase, 102 PUV patients in a first replication phase, and 102 in a second replication phase

Position of the Third Na+ Site in the Aspartate Transporter GltPh and the Human Glutamate Transporter, EAAT1

Glutamate transport via the human excitatory amino acid transporters is coupled to the co-transport of three Na+ ions, one H+ and the counter-transport of one K+ ion. Transport by an archaeal homologue of the human glutamate transporters, GltPh, whose three dimensional structure is known is also coupled to three Na+ ions but only two Na+ ion binding sites have been observed in the crystal structure of GltPh. In order to fully utilize the GltPh structure in functional studies of the human glutamate transporters, it is essential to understand the transport mechanism of GltPh and accurately determine the number and location of Na+ ions coupled to transport. Several sites have been proposed for the binding of a third Na+ ion from electrostatic calculations and molecular dynamics simulations. In this study, we have performed detailed free energy simulations for GltPh and reveal a new site for the third Na+ ion involving the side chains of Threonine 92, Serine 93, Asparagine 310, Aspartate 312, and the backbone of Tyrosine 89. We have also studied the transport properties of alanine mutants of the coordinating residues Threonine 92 and Serine 93 in GltPh, and the corresponding residues in a human glutamate transporter, EAAT1. The mutant transporters have reduced affinity for Na+ compared to their wild type counterparts. These results confirm that Threonine 92 and Serine 93 are involved in the coordination of the third Na+ ion in GltPh and EAAT1

SOLUBLE UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR (SUPAR) SERUM LEVELS PREDICT PROGRESSION OF KIDNEY DISEASE IN CHILDREN

WOS: 000408418900043

Binding free energies for Na⁺ ions in various locations (in kcal/mol).

<p>The interaction energy (ΔG_int), entropic contributions (ΔG_tr) and the total binding energy (ΔG_b) are listed separately. The interaction free energy differences are obtained from the average of the forward and backward transitions. Presence of a second Na⁺ ion is indicated in parentheses. Errors are estimated from block data analysis using 50 ps windows. The Na2 site is not considered because it is formed only after the HP2 gate shuts.</p

Structure of Glt_Ph with bound aspartate, Na1 and Na2 (PDB 2NWX).

<p>(A) One protomer in cartoon representation; transmembrane domain (TM)1, TM2, TM4 and TM5 (coloured in grey), TM3 (blue), TM6 (green), TM7 (orange), TM8 (magenta), hairpin (HP)1 (yellow) and HP2 (red). Bound aspartate is in stick representation and Na1(1) and Na2(2) are indicated as green spheres. (B) Close-up of the substrate binding site that has been rotated 90° around the vertical axis (coloured as in A). Aspartate 312 (D312) and threonine 92 (T92) are shown in stick representation. Figures were made using Pymol <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033058#pone.0033058-Schrodinger1" target="_blank">[39]</a>.</p

The N310 configurations in the closed and open structures contrasted with the MD results.

<p>Comparison of the N310 configuration from the crystal structure (green backbone) with that obtained from MD simulations (cyan backbone). Na⁺ ions are shown as yellow spheres. (A) Closed structure (PDB 2NWX) vs. Na3′ site, (B) Open structure (PDB 2NWW) vs. Na3 site.</p

T92A and S93A mutations in Glt_Ph have reduced Na⁺ affinity.

<p>(A) Size exclusion column profile for wild type Glt_Ph (dark blue), T92A (red), S93A (green), N310A (pink) and D312A (cyan). (B) Uptake of 100 nM ³H-L-aspartate in the presence of 100 mM NaCl for Glt_Ph (black squares), T92A (white squares), S93A (grey squares), N310A (white triangles) and D312A (black triangles). Control levels are from uptake performed in the presence of internal buffer (100 mM KCl, 20 mM HEPES/Tris pH 7.5) (C) ³H-L-aspartate concentration-dependent transport in the presence of 100 mM NaCl by Glt_Ph (black squares), T92A (white squares) and S93A (grey squares). (D) Na⁺ concentration-dependent transport of 100 nM ³H-L-aspartate for Glt_Ph (black squares), T92A (white squares) and 500 nM ³H-L-aspartate for S93A (grey squares). Data in (C) and (D) are normalised to the maximal velocity of transport and all data are from the mean of at least 3 separate experiments ± s.e.m.</p

Effect of the T92A and S93A mutations on the binding free energies of Na⁺ ions at the Na3 and Na1 sites (in kcal/mol).

<p>Mutations significantly reduce the binding free energies of Na3 but not of Na1. Presence of a second Na⁺ ion is indicated in parentheses.</p

T130A and T131A mutations in EAAT1 have reduced Na⁺ affinity.

<p>(A) Amino acid alignment of TM3 and TM7. Alignment was made using ClustalW2 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033058#pone.0033058-Higgins1" target="_blank">[40]</a> and adjusted manually. Amino acid sequences are; human (h)EAAT1 (NP_004163.3), hEAAT2 (NP_004162.2), hEAAT3 (NP_004161.4); hEAAT4 (NP_005062.1); hEAAT5 (NP_006662.3); hASCT1 (NP_003029.2); <i>Pyrococcus horikoshii</i> Glt_Ph (NP_143181); <i>Escherichia coli</i> GltP_Ec (EGT70436.1); <i>Bacillus stearothermophilus</i> GltT_Bs (P24943.1). Red shading indicates the residues that form the Na3 site, grey shading indicates conserved residues and black shading indicates residues absolutely conserved. (B) Average current activated by the application of 100 µM L-glutamate to oocytes clamped at −60 mV expressing EAAT1 (black), T130A (white) and T131A (grey). (C) L-glutamate concentration-dependent currents for EAAT1 (black), T130A (white) and T131A (grey). (D) Na⁺ concentration-dependent currents in the presence of 300 µM L-glutamate for EAAT1 (black circles), and 1 mM L-glutamate for T130A (white circles) and T131A (grey circles). Data in (C) are normalised to the current at saturating glutamate concetrations and all data are from the mean of at least 3 separate experiments ± s.e.m.</p