Whole Earth Telescope observations of the pulsating subdwarf B star PG 0014+067

PG 0014+067 is one of the most promising pulsating subdwarf B stars for seismic analysis, as it has a rich pulsation spectrum. The richness of its pulsations, however, poses a fundamental challenge to understanding the pulsations of these stars, as the mode density is too complex to be explained only with radial and nonradial low degree (l < 3) p-modes without rotational splittings. One proposed solution, for the case of PG 0014+067 in particular, assigns some modes with high degree (l=3). On the other hand, theoretical models of sdB stars suggest that they may retain rapidly rotating cores, and so the high mode density may result from the presence of a few rotationally-split triplet (l=1), quintuplet (l=2) modes, along with radial (l=0) p-modes. To examine alternative theoretical models for these stars, we need better frequency resolution and denser longitude coverage. Therefore, we observed this star with the Whole Earth Telescope for two weeks in October 2004. In this paper we report the results of Whole Earth Telescope observations of the pulsating subdwarf B star PG 0014+067. We find that the frequencies seen in PG 0014+067 do not appear to fit any theoretical model currently available; however, we find a simple empirical relation that is able to match all of the well-determined frequencies in this star.Comment: 19 pages, preprint of paper accepted for publication in The Astrophysical Journa

Specific and highly efficient condensation of GC and IC DNA by polyaza pyridinophane derivatives

Two bis-polyaza pyridinophane derivatives and their monomeric reference compounds revealed strong interactions with ds-DNA and RNA. The bis-derivatives show a specific condensation of GC- and IC-DNA, which is almost two orders of magnitude more efficient than the well-known condensation agent spermine. The type of condensed DNA was identified as psi-DNA, characterized by the exceptionally strong CD signals. At variance to the almost silent AT(U) polynucleotides, these strong CD signals allow the determination of GC-condensates at nanomolar nucleobase concentrations. Detailed thermodynamic characterisation by ITC reveals significant differences between the DNA binding of the bis- derivative compounds (enthalpy driven) and that of spermine and of their monomeric counterparts (entropy driven). Atomic force microscopy confirmed GC-DNA compaction by the bis-derivatives and the formation of toroid- and rod-like structures responsible for the psi-type pattern in the CD spectra

Thermodynamic Penalty Arising from Burial of a Ligand Polar Group Within a Hydrophobic Pocket of a Protein Receptor

Here, we examine the thermodynamic penalty arising from burial of a polar group in a hydrophobic pocket that forms part of the binding-site of the major urinary protein (MUP-I). X-ray crystal structures of the complexes of octanol, nonanol and 1,8 octan-diol indicate that these ligands bind with similar orientations in the binding pocket. Each complex is characterised by a bridging water molecule between the hydroxyl group of Tyr120 and the hydroxyl group of each ligand. The additional hydroxyl group of 1,8 octan-diol is thereby forced to reside in a hydrophobic pocket, and isothermal titration calorimetry experiments indicate that this is accompanied by a standard free energy penalty of + 21 kJ/mol with respect to octanol and + 18 kJ/mol with respect to nonanol. Consideration of the solvation thermodynamics of each ligand enables the “intrinsic” (solute–solute) interaction energy to be determined, which indicates a favourable enthalpic component and an entropic component that is small or zero. These data indicate that the thermodynamic penalty to binding derived from the unfavourable desolvation of 1,8 octan-diol is partially offset by a favourable intrinsic contribution. Quantum chemical calculations suggest that this latter contribution derives from favourable solute–solute dispersion interactions

Comparison of Entropic Contributions to Binding in a “Hydrophilic” versus “Hydrophobic” Ligand−Protein Interaction

In the present study we characterize the thermodynamics of binding of histamine to recombinant histamine-binding protein (rRaHBP2), a member of the lipocalin family isolated from the brown-ear tick <i>Rhipicephalus appendiculatus</i>. The binding pocket of this protein contains a number of charged residues, consistent with histamine binding, and is thus a typical example of a “hydrophilic” binder. In contrast, a second member of the lipocalin family, the recombinant major urinary protein (rMUP), binds small hydrophobic ligands, with a similar overall entropy of binding in comparison with rRaHBP2. Having extensively studied ligand binding thermodynamics for rMUP previously, the data we obtained in the present study for HBP enables a comparison of the driving forces for binding between these classically distinct binding processes in terms of entropic contributions from ligand, protein, and solvent. In the case of rRaHBP2, we find favorable entropic contributions to binding from desolvation of the ligand; however, the overall entropy of binding is unfavorable due to a dominant unfavorable contribution arising from the loss of ligand degrees of freedom, together with the sequestration of solvent water molecules into the binding pocket in the complex. This contrasts with binding in rMUP where desolvation of the protein binding pocket makes a minor contribution to the overall entropy of binding given that the pocket is substantially desolvated prior to binding

NDP52 acts as a redox sensor in PINK1/Parkin-mediated mitophagy

Mitophagy, the elimination of mitochondria via the autophagy-lysosome pathway, is essential for the maintenance of cellular homeostasis. The best characterised mitophagy pathway is mediated by stabilisation of the protein kinase PINK1 and recruitment of the ubiquitin ligase Parkin to damaged mitochondria. Ubiquitinated mitochondrial surface proteins are recognised by autophagy receptors including NDP52 which initiate the formation of an autophagic vesicle around the mitochondria. Damaged mitochondria also generate reactive oxygen species (ROS) which have been proposed to act as a signal for mitophagy, however the mechanism of ROS sensing is unknown. Here we found that oxidation of NDP52 is essential for the efficient PINK1/Parkin-dependent mitophagy. We identified redox-sensitive cysteine residues involved in disulphide bond formation and oligomerisation of NDP52 on damaged mitochondria. Oligomerisation of NDP52 facilitates the recruitment of autophagy machinery for rapid mitochondrial degradation. We propose that redox sensing by NDP52 allows mitophagy to function as a mechanism of oxidative stress response

Residual Ligand Entropy in the Binding of <i>p</i>-Substituted Benzenesulfonamide Ligands to Bovine Carbonic Anhydrase II

In studies on the thermodynamics of ligand−protein interactions, it is often assumed that the configurational and conformational entropy of the ligand is zero in the bound state (i.e., the ligand is rigidly fixed in the binding pocket). However, there is little direct experimental evidence for this assumption, and in the case of binding of <i>p</i>-substituted benzenesulfonamide inhibitors to bovine carbonic anhydrase II (BCA II), the observed thermodynamic binding signature derived from isothermal titration calorimetry experiments leads indirectly to the conclusion that a considerable degree of residual entropy remains in the bound ligand. Specifically, the entropy of binding increases with glycine chain length <i>n</i>, and strong evidence exists that this thermodynamic signature is not driven by solvent reorganization. By use of heteronuclear ¹⁵N NMR relaxation measurements in a series (<i>n</i> = 1−6) of ¹⁵N-glycine-enriched ligands, we find that the observed thermodynamic binding signature cannot be explained by residual ligand dynamics in the bound state, but rather results from the indirect influence of ligand chain length on protein dynamics