Superconductive sodalite-like clathrate calcium hydride at high pressures

Hydrogen-rich compounds hold promise as high-temperature superconductors under high pressures. Recent theoretical hydride structures on achieving high-pressure superconductivity are composed mainly of H₂ fragments. Through a systematic investigation of Ca hydrides with different hydrogen contents using particle-swam optimization structural search, we show that in the stoichiometry CaH₆ a body-centered cubic structure with hydrogen that forms unusual “sodalite” cages containing enclathrated Ca stabilizes above pressure 150 GPa. The stability of this structure is derived from the acceptance by two H₂ of electrons donated by Ca forming an “H₄” unit as the building block in the construction of the three-dimensional sodalite cage. This unique structure has a partial occupation of the degenerated orbitals at the zone center. The resultant dynamic Jahn–Teller effect helps to enhance electron–phonon coupling and leads to superconductivity of CaH₆. A superconducting critical temperature (T_c) of 220–235 K at 150 GPa obtained from the solution of the Eliashberg equations is the highest among all hydrides studied thus far.     

Room temperature femtosecond X-ray diffraction of photosystem II microcrystals

Most of the dioxygen on earth is generated by the oxidation of water by photosystem II (PS II) using light from the sun. This light-driven, four-photon reaction is catalyzed by the Mn₄CaO₅ cluster located at the lumenal side of PS II. Various X-ray studies have been carried out at cryogenic temperatures to understand the intermediate steps involved in the water oxidation mechanism. However, the necessity for collecting data at room temperature, especially for studying the transient steps during the O–O bond formation, requires the development of new methodologies. In this paper we report room temperature X-ray diffraction data of PS II microcrystals obtained using ultrashort (< 50 fs) 9 keV X-ray pulses from a hard X-ray free electron laser, namely the Linac Coherent Light Source. The results presented here demonstrate that the ”probe before destroy” approach using an X-ray free electron laser works even for the highly-sensitive Mn₄CaO₅ cluster in PS II at room temperature. We show that these data are comparable to those obtained in synchrotron radiation studies as seen by the similarities in the overall structure of the helices, the protein subunits and the location of the various cofactors. This work is, therefore, an important step toward future studies for resolving the structure of the Mn₄CaO₅ cluster without any damage at room temperature, and of the reaction intermediates of PS II during O–O bond formation.     

Approximately diagonalizing matrices over C(Y)

Let X be a compact metric space which is locally absolutely retract and let φ: C(X) → C(Y,M_n) be a unital homomorphism, where Y is a compact metric space with dim Y ≤ 2. It is proved that there exists a sequence of n continuous maps α_i,m: Y → X (i = 1,2,…,n) and a sequence of sets of mutually orthogonal rank-one projections {p_1,m,p_2,m,…,p_n,m}⊂C(Y,M_n) such that This is closely related to the Kadison diagonal matrix question. It is also shown that this approximate diagonalization could not hold in general when dim Y≥3.     

From the Cover: Symmetric tangled Platonic polyhedra

Conventional embeddings of the edge-graphs of Platonic polyhedra, {f, z}, where f, z denote the number of edges in each face and the edge-valence at each vertex, respectively, are untangled in that they can be placed on a sphere (S2) such that distinct edges do not intersect, analogous to unknotted loops, which allow crossing-free drawings of S1 on the sphere. The most symmetric (flag-transitive) realizations of those polyhedral graphs are those of the classical Platonic polyhedra, whose symmetries are *2fz, according to Conway’s two-dimensional (2D) orbifold notation (equivalent to Schönflies symbols I_h, O_h, and T_d). Tangled Platonic {f, z} polyhedra—which cannot lie on the sphere without edge-crossings—are constructed as windings of helices with three, five, seven,… strands on multigenus surfaces formed by tubifying the edges of conventional Platonic polyhedra, have (chiral) symmetries 2fz (I, O, and T), whose vertices, edges, and faces are symmetrically identical, realized with two flags. The analysis extends to the “θ_z” polyhedra, {2,z}. The vertices of these symmetric tangled polyhedra overlap with those of the Platonic polyhedra; however, their helicity requires curvilinear (or kinked) edges in all but one case. We show that these 2fz polyhedral tangles are maximally symmetric; more symmetric embeddings are necessarily untangled. On one hand, their topologies are very constrained: They are either self-entangled graphs (analogous to knots) or mutually catenated entangled compound polyhedra (analogous to links). On the other hand, an endless variety of entanglements can be realized for each topology. Simpler examples resemble patterns observed in synthetic organometallic materials and clathrin coats in vivo.

Two-dimensional topology, graph theory, and non-Euclidean geometry offer a useful view of the rich universe of chemical structures. In this paper, we combine Platonic geometry and two-dimensional topology to derive theoretical families of “tangled” or “catenated” polyhedra, whose faces are threaded by edges. (We will clarify our nomenclature later on.) The resulting structures are worth knowing for their own sake, since they are the most symmetric entanglements of the regular (Platonic) polyhedra in three-dimensional space, with symmetrically equivalent faces, edges, and vertices. They are also promising candidates for (supra)molecular assemblies. For example, tangled symmetric structures are a feature of finite metal-organic molecules (1–5) and infinite catenated inorganic compounds, coordination polymers, covalent organic frameworks (COFs), and metal-organic frameworks (MOFs) (6–12).The phenomenon of entanglement is central to the mathematical field of knot theory (13). Equivalent tangled nets are “isotopic” and interchangeable by any distortion of the net edges and vertices as long as edges don’t pass through each other. Tangling is therefore a structural phenomenon that lies between geometrically congruent structures, which allow rigid-body rotations or translations only, and topologically equivalent (homeomorphic) structures, which can be interchanged by arbitrary distortions, including “phantom moves” of edges through each other. In common with modern understanding of polyhedra as combinatorial structures (14), we describe polyhedra via the net of edges and vertices, allowing faces to self-intersect. However, we do not insist that edges follow shortest paths between vertices, allowing edges to tangle. For example, tangled cubes share the topology of the conventional Platonic cube, but many different “isotopes” are possible, whose rings of four edges—bounding the cube “faces”—are threaded by edges in different ways (some examples can be found in ref. 15). The occurrence of tangled two- and three-periodic nets at the molecular scale in synthetic chemical materials, particularly MOFs, has led to a number of fundamental studies of tangles of infinite periodic nets (10, 16–19). In contrast, surprisingly little is known about allowed symmetries of finite nets, with the exception of the “trivial” (untangled) symmetric (e.g., Platonic and Archimedean) polyhedra and studies of symmetric embeddings of knots and links (20–22). Graph topologies of the five Platonic polyhedral nets are given by their Schläfli symbols, {f, z}, where f describes the number of edges per face and z the number of faces per vertex (z), including {3, 3} (tetrahedron), {3, 4} (octahedron), {4, 3} (cube), {3, 5} (icosahedron), and {5, 3} (dodecahedron). We describe the familiar regular embeddings of these nets, with straight edges, as (capitalized) “Platonic” embeddings and arbitrary embeddings of {f, z} nets as “platonic”. The former are “flag-transitive” embeddings of {f, z} nets with symmetrically identical faces, edges, and vertices; their point-group symmetries are (for our purposes) most simply denoted by Conway’s orbifold symbols *2fz (23). The orbifolds refer to the symmetries of spherical embeddings of the Platonic polyhedra, formed by blowing the polyhedra into a ball, bounded by a sphere centered on the polyhedron. The radius of that sphere can be adjusted so that all polyhedral vertices lie on its surface and edges form arcs of great circles joining those vertices. Conway symbols *2fz describe the asymmetric domain of those spherical Platonic polyhedra: spherical triangles bounded by geodesic mirror arcs (on great circles) subtending angles on the sphere of π2, πf, and πz. The geodesic edges coincide with the intersections of mirror planes of the Platonic polyhedron with the sphere, passing through face centers, vertices, and midedges, giving Schönflies point-group symbols, T_d, O_h, and I_h (for {3, 3}, {4, 3} or {3, 4}, and {5, 3} or {3, 5}, respectively) (24).Graph topologies of the nets of platonic polyhedra are constrained by Euler’s formula for polyhedra, which can be expressed as 0≤(f−2)(z−2)<4, where f and z are positive integers. That relation admits additional solutions, notably, the {2, 3} “θ-polyhedron,” with a pair of three-valent vertices and three lens-shaped faces. That net can be embedded in space with symmetry *223, in which case its three edges describe curved meridians from pole to pole. More generally, θ_z-polyhedra, with vertices at both poles joined by z meridians, are admissible solutions. For convenience, we include the θ_z-polyhedra among platonic examples. All of these platonic {f, z} polyhedra can be embedded as “regular” (Platonic) polyhedra, with reflection symmetry *2fz.The most symmetric “irregular” polyhedra are referred to as “chiral polytopes” in ref. 25. So-called chiral polytopes are almost, but not quite, regular: Like regular polyhedra, they have edge-, vertex-, and face-transitive embeddings. However, in contrast to regular cases which have a single flag, chiral polytopes have two distinct flags, each with separate orbits. Any flag of one type is necessarily adjacent to a flag of the other, and their union describes an asymmetric domain of the chiral embedding (25). (Three-dimensional chiral polytopes differ from better-known chiral polyhedra, such as the snub cube, although both are geometrically chiral.) Chiral polytopes, with straight edges, include either an infinite number of finite (skew) faces or a finite number of infinite (helical) faces (25), Here, we show that specific entanglements of {f, z} polyhedra, whose nets share the topologies of Platonic polyhedra, can be realized with symmetries 2fz, which contain rotation axes only (Schönflies point-group symbols T, O, and I for {3, 3}, {4, 3} or {3, 4}, and {5, 3} or {3, 5}, respectively). The edge-net of a tangled platonic {f, z} polyhedron cannot be morphed into that of its untangled Platonic analog without phantom crossings, where edges pass through each other. Like chiral polytopes, these tangled polyhedra have just two flags; they are therefore the most symmetric nontrivial embeddings of entangled platonic graphs, whose trivial entanglements are the Platonic *2fz polyhedral embeddings.Embeddings of Platonic {f, z} polyhedra with no crossed edges are possible on the sphere; their edges can therefore be traced in the plane without edge-crossings (e.g., via stereographic projection). These regular embeddings are classified as “untangled,” analogous to the trivial unknot, which can be drawn in the plane (or on the sphere) without edge-crossings. In contrast, like knots, planar drawings of tangled net embeddings contain edge-crossings, and crossing-free embeddings are possible only on higher-genus surfaces. Tangled embeddings of polyhedral nets {f, z} are less symmetric than their untangled, regular analogs. Earlier studies of tangled nets of the tetrahedron, octahedron, and cube, generated as reticulations of the relevant {f, z} nets on the torus, established that all such “toroidal polyhedra” are topologically chiral (26, 27), allowing a pair of distinct isotopes related to each other by a reflection. Further, those toroidal polyhedra are, without exception, rather asymmetric compared with their untangled embeddings. Their chirality ensures that they are devoid of reflections (so their orbifold symbols exclude the * character) and have multiple flags. The most symmetric toroidal tetrahedra, cubes, and octahedra can be realized with orbifolds 222 (D₂), 422 (D₄), and 622 (D₆), respectively (28), with six, six, and four distinct flags. Here, we show that the most symmetric {f, z} (nontrivially) tangled polyhedral nets can be embedded in space with chiral symmetry 2fz, provided their edges are curved (or suitably kinked), so that they have just two flags, analogous to chiral polytopes. Since the most symmetric regular embeddings of polyhedral graphs {f, z}, with symmetry *2fz, are untangled, these 2fz cases are the most symmetric possible embeddings of (nontrivial) polyhedral entanglements.     

Photoelectron spectroscopic and computational studies of the Pt@Pb₁₀⁻¹ and Pt@Pb₁₂¹⁻/²⁻ anions

A combination of anion photoelectron spectroscopy and density functional theory calculations has elucidated the geometric and electronic structure of gas-phase endohedral Pt/Pb cage cluster anions. The anions, and were prepared from “preassembled” clusters generated from crystalline samples of [K(2,2,2-crypt)]₂[Pt @ Pb₁₂] that were brought into the gas phase using a unique infrared desorption/photoemission anion source. The use of crystalline [K(2,2,2-crypt)]₂[Pt @ Pb₁₂] also provided access to K[Pt @ Pb_n]^- anions in the gas phase (i.e., the K⁺ salts of the anions). Anion photoelectron spectra of , , and K[Pt @ Pb₁₂]^1- are presented. Extensive density functional theory calculations on and provided candidate structures and anion photoelectron spectra for and . Together, the calculated and measured photoelectron spectra show that and endohedral complexes maintain their respective D_4d and slightly distorted I_h symmetries in the gas phase even for the charge states with open shell character. Aside from the fullerenes, the endohedral complex is the only bare cluster that has been structurally characterized in the solid state, solution, and the gas phase.     

Energetics of Al₁₃ Keggin cluster compounds

The ϵ-Al₁₃ Keggin aluminum hydroxide clusters are essential models in establishing molecular pathways for geochemical reactions. Enthalpies of formation are reported for two salts of aluminum centered ϵ-Keggin clusters, Al₁₃ selenate, (Na(AlO₄)Al₁₂(OH)₂₄(SeO₄)₄•12H₂O) and Al₁₃ sulfate, (NaAlO₄Al₁₂(OH)₂₄(SO₄)₄•12H₂O). The measured enthalpies of solution, ΔH_sol, at 28 °C in 5 N HCl for the ε-Al₁₃ selenate and sulfate are −924.57 (± 3.83) and −944.30 ( ± 5.66) kJ·mol^-1, respectively. The enthalpies of formation from the elements, ΔH_f,el, for Al₁₃ selenate and sulfate are −19,656.35 ( ± 67.30) kJ·mol^-1, and −20,892.39 ( ± 70.01) kJ·mol^-1, respectively. In addition, ΔH_f,el for sodium selenate decahydrate was calculated using data from high temperature oxide melt solution calorimetry measurements: −4,006.39 ( ± 11.91) kJ·mol^-1. The formation of both ε-Al₁₃ Keggin cluster compounds is exothermic from oxide-based components but energetically unfavorable with respect to a gibbsite-based assemblage. To understand the relative affinity of the ϵ-Keggin clusters for selenate and sulfate, the enthalpy associated with two S-Se exchange reactions was calculated. In the solid state, selenium is favored in the Al₁₃ compound relative to the binary chalcogenate, while in 5 N HCl, sulfur is energetically favored in the cluster compound compared to the aqueous solution. This contribution represents the first thermodynamic study of ε-Al₁₃ cluster compounds and establishes a method for other such molecules, including the substituted versions that have been created for kinetic studies. Underscoring the importance of ε-Al₁₃ clusters in natural and anthropogenic systems, these data provide conclusive thermodynamic evidence that the Al₁₃ Keggin cluster is a crucial intermediate species in the formation pathway from aqueous aluminum monomers to aluminum hydroxide precipitates.     

The relationship between the frequency of self‐monitoring of blood glucose and glycemic control in patients with type 1 diabetes mellitus on continuous subcutaneous insulin infusion or on multiple daily injections

Aims/Introduction

We investigated the relationship between the frequency of self-monitoring of blood glucose (SMBG) and glycemic control in type 1 diabetes mellitus patients on continuous subcutaneous insulin infusion (CSII) or on multiple daily injections (MDI) using data management software.

Materials and Methods

We recruited 148 adult type 1 diabetes mellitus patients (CSII n = 42, MDI n = 106) and downloaded their SMBG records to the MEQNET™ SMBG Viewer software (Arkray Inc., Kyoto, Japan). The association between the SMBG frequency and the patients'' hemoglobin A1c (HbA1c) levels was analyzed using the χ²-test and linear regression analysis was carried out to clarify their relationship.

Results

The odds ratio of achieving a target HbA1c level of <8% (63.9 mmol/mol) was significantly higher in subjects with SMBG frequencies of ≥3.5 times/day compared with those with SMBG frequencies of <3.5 times/day in the CSII group (odds ratio 7.00, 95% confidence interval 1.72–28.54), but not in the MDI group (odds ratio 1.35, 95% CI 0.62–2.93). A significant correlation between SMBG frequency and the HbA1c level was detected in the CSII group (HbA1c [%] = –0.24 × SMBG frequency [times/day] + 8.60 [HbA1c {mmol/L} = –2.61 × SMBG frequency {times/day} + 70.5], [r = –0.384, P = 0.012]), but not in the MDI group.

Conclusions

A SMBG frequency of <3.5 times per day appeared to be a risk factor for poor glycemic control (HbA1c ≥8%) in type 1 diabetes mellitus patients on CSII.     

Unification of reaction pathway and kinetic scheme for N2 reduction catalyzed by nitrogenase

Nitrogenase catalyzes the reduction of N₂ and protons to yield two NH₃ and one H₂. Substrate binding occurs at a complex organo-metallocluster called FeMo-cofactor (FeMo-co). Each catalytic cycle involves the sequential delivery of eight electrons/protons to this cluster, and this process has been framed within a kinetic scheme developed by Lowe and Thorneley. Rapid freezing of a modified nitrogenase under turnover conditions using diazene, methyldiazene (HN = N-CH₃), or hydrazine as substrate recently was shown to trap a common intermediate, designated I. It was further concluded that the two N-atoms of N₂ are hydrogenated alternately (“Alternating” (A) pathway). In the present work, Q-band CW EPR and ⁹⁵Mo ESEEM spectroscopy reveal such samples also contain a common intermediate with FeMo-co in an integer-spin state having a ground-state “non-Kramers” doublet. This species, designated H, has been characterized by ESEEM spectroscopy using a combination of ^14,15N isotopologs plus ^1,2H isotopologs of methyldiazene. It is concluded that: H has NH₂ bound to FeMo-co and corresponds to the penultimate intermediate of N₂ hydrogenation, the state formed after the accumulation of seven electrons/protons and the release of the first NH₃; I corresponds to the final intermediate in N₂ reduction, the state formed after accumulation of eight electrons/protons, with NH₃ still bound to FeMo-co prior to release and regeneration of resting-state FeMo-co. A proposed unification of the Lowe-Thorneley kinetic model with the “prompt” alternating reaction pathway represents a draft mechanism for N₂ reduction by nitrogenase.     

Redox systematics of a magma ocean with variable pressure-temperature gradients and composition

Oxygen fugacity in metal-bearing systems controls some fundamental aspects of the geochemistry of the early Earth, such as the FeO and siderophile trace element content of the mantle, volatile species that influence atmospheric composition, and conditions for organic compounds synthesis. Redox and metal-silicate equilibria in the early Earth are sensitive to oxygen fugacity (fO₂), yet are poorly constrained in modeling and experimentation. High pressure and temperature experimentation and modeling in metal-silicate systems usually employs an approximation approach for estimating fO₂ that is based on the ratio of Fe and FeO [called “ΔIW (ratio)” hereafter]. We present a new approach that utilizes free energy and activity modeling of the equilibrium: Fe + SiO₂ + O₂ = Fe₂SiO₄ to calculate absolute fO₂ and relative to the iron-wüstite (IW) buffer at pressure and temperature [ΔIW (P,T)]. This equilibrium is considered across a wide range of pressures and temperatures, including up to the liquidus temperature of peridotite (4,000 K at 50 GPa). Application of ΔIW (ratio) to metal-silicate experiments can be three or four orders of magnitude different from ΔIW (P,T) values calculated using free energy and activity modeling. We will also use this approach to consider the variation in oxygen fugacity in a magma ocean scenario for various thermal structures for the early Earth: hot liquidus gradient, 100 °C below the liquidus, hot and cool adiabatic gradients, and a cool subsolidus adiabat. The results are used to assess the effect of increasing P and T, changing silicate composition during accretion, and related to current models for accretion and core formation in the Earth. The fO₂ in a deep magma ocean scenario may become lower relative to the IW buffer at hotter and deeper conditions, which could include metal entrainment scenarios. Therefore, fO₂ may evolve from high to low fO₂ during Earth (and other differentiated bodies) accretion. Any modeling of core formation and metal-silicate equilibrium should take these effects into account.     

Novel Composite Nitride Nanoceramics from Reaction-Mixed Nanocrystalline Powders in the System Aluminum Nitride AlN/Gallium Nitride GaN/Titanium Nitride TiN (Al:Ga:Ti = 1:1:1)

A study is presented on the synthesis of reaction-mixed nitride nanopowders in the reference system of aluminium nitride AlN, gallium nitride GaN, and titanium nitride TiN (Al:Ga:Ti = 1:1:1) followed by their high-pressure and high-temperature sintering towards novel multi-nitride composite nanoceramics. The synthesis starts with a 4 h reflux in hexane of the mixture of the respective metal dimethylamides, which is followed by hexane evacuation, and reactions of the residue in liquid ammonia at −33 °C to afford a mixed metal amide/imide precursor. Plausible equilibration towards a bimetallic Al/Ga-dimethylamide compound upon mixing of the solutions of the individual metal-dimethylamide precursors containing dimeric {Al[N(CH₃)₂]₃}₂ and dimeric {Ga[N(CH₃)₂]₃}₂ is confirmed by ¹H- and ¹³C{H}-NMR spectroscopy in C₆D₆ solution. The precursor is pyrolyzed under ammonia at 800 and 950 °C yielding, respectively, two different reaction-mixed composite nitride nanopowders. The latter are subjected to no-additive high-pressure and high-temperature sintering under conditions either conservative for the initial powder nanocrystallinity (650 °C, 7.7 GPa) or promoting crystal growth/recrystallization and, possibly, solid solution formation via reactions of AlN and GaN towards Al_0.5Ga_0.5N (1000 and 1100 °C, 7.7 GPa). The sintered composite pellets show moderately high mechanical hardness as determined by the Vicker’s method. The starting nanopowders and resulting nanoceramics are characterized by powder XRD, Raman spectroscopy, and SEM/EDX. It is demonstrated that, in addition to the multi-nitride composite nanoceramics of hexagonal AlN/hexagonal GaN/cubic TiN, under specific conditions the novel composite nanoceramics made of hexagonal Al_0.5Ga_0.5N and cubic TiN can be prepared.     

Resolvent positive linear operators exhibit the reduction phenomenon

The spectral bound, s(αA + βV), of a combination of a resolvent positive linear operator A and an operator of multiplication V, was shown by Kato to be convex in . Kato''s result is shown here to imply, through an elementary “dual convexity” lemma, that s(αA + βV) is also convex in α > 0, and notably, ∂s(αA + βV)/∂α ≤ s(A). Diffusions typically have s(A) ≤ 0, so that for diffusions with spatially heterogeneous growth or decay rates, greater mixing reduces growth. Models of the evolution of dispersal in particular have found this result when A is a Laplacian or second-order elliptic operator, or a nonlocal diffusion operator, implying selection for reduced dispersal. These cases are shown here to be part of a single, broadly general, “reduction” phenomenon.     

Engineering a protein-protein interface using a computationally designed library

Computational algorithms for protein design can sample large regions of sequence space, but suffer from undersampling of conformational space and energy function inaccuracies. Experimental screening of combinatorial protein libraries avoids the need for accurate energy functions, but has limited access to vast amounts of sequence space. Here, we test if these two traditionally alternative, but potentially complementary approaches can be combined to design a variant of the ubiquitin-ligase E6AP that will bind to a nonnatural partner, the NEDD8-conjugating enzyme Ubc12. Three E6AP libraries were constructed: (i) a naive library in which all 20 amino acids were allowed at every position on the target-binding surface of E6AP (13 positions), (ii) a semidirected library that varied the same residue positions as in the naive library but disallowed mutations computationally predicted to destabilize E6AP, and (iii) a directed library that used docking and sequence optimization simulations to identify mutations predicted to be favorable for binding Ubc12. Both of the directed libraries showed > 30-fold enrichment over the naive library after the first round of screening with a split-dihydrofolate reductase complementation assay and produced multiple tight binders (K_d < 100 nM) after four rounds of selection. Four rounds of selection with the naive library failed to produce any binders with K_d’s lower than 50 μM. These results indicate that protein design simulations can be used to create directed libraries that are enriched in tight binders and that in some cases it is sufficient to computationally screen for well-folded sequences without explicit binding calculations.     

Structure of the 26S proteasome from Schizosaccharomyces pombe at subnanometer resolution

The structure of the 26S proteasome from Schizosaccharomyces pombe has been determined to a resolution of 9.1 Å by cryoelectron microscopy and single particle analysis. In addition, chemical cross-linking in conjunction with mass spectrometry has been used to identify numerous residue pairs in close proximity to each other, providing an array of spatial restraints. Taken together these data clarify the topology of the AAA-ATPase module in the 19S regulatory particle and its spatial relationship to the α-ring of the 20S core particle. Image classification and variance analysis reveal a belt of high “activity” surrounding the AAA-ATPase module which is tentatively assigned to the reversible association of proteasome interacting proteins and the conformational heterogeneity among the particles. An integrated model is presented which sheds light on the early steps of protein degradation by the 26S complex.     

Two distinct overstretched DNA structures revealed by single-molecule thermodynamics measurements

Double-stranded DNA is a dynamic molecule whose structure can change depending on conditions. While there is consensus in the literature about many structures DNA can have, the state of highly-stretched DNA is still not clear. Several groups have shown that DNA in the torsion-unconstrained B-form undergoes an “overstretching” transition at a stretching force of around 65 pN, which leads to approximately 1.7-fold elongation of the DNA contour length. Recent experiments have revealed that two distinct structural transitions are involved in the overstretching process: (i) a hysteretic “peeling” off one strand from its complementary strand, and (ii) a nonhysteretic transition that leads to an undetermined DNA structure. We report the first simultaneous determination of the entropy (ΔS) and enthalpy changes (ΔH) pertaining to these respective transitions. For the hysteretic peeling transition, we determined ΔS ∼ 20 cal/(K.mol) and ΔH ∼ 7 kcal/mol. In the case of the nonhysteretic transition, ΔS ∼ -3 cal/(K.mol) and ΔH ∼ 1 kcal/mol. Furthermore, the response of the transition force to salt concentration implies that the two DNA strands are spatially separated after the hysteretic peeling transition. In contrast, the corresponding response after the nonhysteretic transition indicated that the strands remained in close proximity. The selection between the two transitions depends on DNA base-pair stability, and it can be illustrated by a multidimensional phase diagram. Our results provide important insights into the thermodynamics of DNA overstretching and conformational structures of overstretched DNA that may play an important role in vivo.     

Asthma Beliefs Are Associated with Medication Adherence in Older Asthmatics

BACKGROUND

Empirical research and health policies on asthma have focused on children and young adults, even though asthma morbidity and mortality are higher among older asthmatics.

OBJECTIVE

To explore the relationship of asthma-related beliefs and self-reported controller medication adherence in older asthmatics.

DESIGN

An observational study of asthma beliefs and self-management among older adults.

PARTICIPANTS

Asthmatics ages ≥60 years (N = 324, mean age 67.4 ± 6.8, 28 % white, 32 % black, 30 % Hispanic) were recruited from primary care practices in New York City and Chicago.

MAIN MEASURES

Self-reported controller medication adherence was assessed using the Medication Adherence Report Scale. Based on the Common Sense Model of Self-Regulation, patients were asked if they believe they only have asthma with symptoms, their physician can cure their asthma, and if their asthma will persist. Beliefs on the benefit, necessity and concerns of treatment use were also assessed. Multivariate logistic regression was used to examine the association of beliefs with self-reported medication adherence.

KEY RESULTS

The majority (57.0 %) of patients reported poor adherence. Poor self-reported adherence was more common among those with erroneous beliefs about asthma illness and treatments, including the “no symptoms, no asthma” belief (58.7 % vs. 31.7 %, respectively, p < 0.001), “will not always have asthma” belief (34.8 % vs. 12.5 %, p < 0.001), and the “MD can cure asthma” belief (21.7 % vs. 9.6 %, p = 0.01). Adjusting for illness beliefs, treatment beliefs and demographics, patients with a “no symptoms, no asthma” belief had lower odds of having good self-reported adherence (odds ratio [OR] 0.45, 95 % confidence interval [CI] 0.23-0.86), as did those with negative beliefs about the benefits (OR 0.73, 95 % CI 0.57-0.94) and necessity (OR 0.89, 95 % CI 0.83-0.96) of treatment.

CONCLUSIONS

Illness and treatment beliefs have a strong influence on self-reported medication adherence in older asthmatics. Interventions to improve medication adherence in older asthmatics by modifying illness and treatment beliefs warrant study.

Electronic supplementary material

The online version of this article (doi:10.1007/s11606-012-2160-z) contains supplementary material, which is available to authorized users.KEY WORDS: asthma, disease management, medication adherence, aging, health beliefs.     

Resting heart rate in patients with ischemic heart disease in Saudi Arabia and Egypt

Aim

To assess the level of resting heart rate (RHR) in an outpatient population presenting with stable coronary artery disease (CAD) as well as to measure its association with current therapeutic management strategies for cardiovascular events.

Materials and methods

A multi-center cross-sectional survey was carried out in Saudi Arabia and Egypt over a three month period (between January 2007 and April 2007). 2049 patients with CAD without clinical heart failure (HF) were included in this study through “cluster sampling”. RHR was measured by manual palpitation.

Results

Mean age of CAD patients was 56.7 ± 10.4 and the mean RHR was 78.9 ± 13.9 b/m. 1686 patients (83.1%) were on β-blockers for whom the RHR was 78.5 ± 14.0 b/m (95.5% had RHR ⩾ 60 b/m, which is higher than recommended by the guidelines). 1094 (73.5%) of patients on β-blockers were on a lower dose, probably to avoid the complications associated with such a class. Among those not on β-blockers (16.9%), RHR was 80.9 ± 13.0 b/m.Moreover, 98 patients (4.8%) were on calcium channel blocker (diltiazem or verapamil) but not on β-blockers, for whom the RHR was 80.9 ± 12.0 b/m. Finally, 163 patients (8.0%) were on both β-blockers and the calcium channel blocker, and their RHR was 79.0 ± 14.4 b/m.

Conclusion

Optimal target RHR has not been achieved in a significant number of screened patients. Achievements of such targets are known to decrease mortality and to improve survival.Abbreviations: RHR, resting heart rate; CAD, coronary artery disease; NYHA, New York Heart Association Classification; HF, heart failure     

Structural basis for substrate activation and regulation by cystathionine beta-synthase (CBS) domains in cystathionine {beta}-synthase

The catalytic potential for H₂S biogenesis and homocysteine clearance converge at the active site of cystathionine β-synthase (CBS), a pyridoxal phosphate-dependent enzyme. CBS catalyzes β-replacement reactions of either serine or cysteine by homocysteine to give cystathionine and water or H₂S, respectively. In this study, high-resolution structures of the full-length enzyme from Drosophila in which a carbanion (1.70 Å) and an aminoacrylate intermediate (1.55 Å) have been captured are reported. Electrostatic stabilization of the zwitterionic carbanion intermediate is afforded by the close positioning of an active site lysine residue that is initially used for Schiff base formation in the internal aldimine and later as a general base. Additional stabilizing interactions between active site residues and the catalytic intermediates are observed. Furthermore, the structure of the regulatory “energy-sensing” CBS domains, named after this protein, suggests a mechanism for allosteric activation by S-adenosylmethionine.     

Interrelationships between vitamin D3 and 25-Hydroxyvitamin D3 during chronic ethanol administration in the rat

Vitamin D {D} depleted female Sprague-Dawley rats were fed for a period of 4 wk a D deficient diet containing 36% of total calories as ethanol while control animals received an isocaloric regimen where ethanol was substituted for by dextrins. In conjunction with the ethanol feeding 92 I.U. of {¹⁴C}-vitamin D₃ {{¹⁴C}-D₃} were administered by intragastric gavage 3 times 1 wk for 3 $\text{2}\text{3}$ wk. At the end of the experiment, {¹⁴C}-D₃ and {¹⁴C}-25-hydroxyvitamin D₃ {{¹⁴C}-25(OH)D₃} concentrations were analyzed in plasma, liver, striated muscle and adipose tissue. Body reserves in unchanged {¹⁴C}-D₃ were significantly reduced by ethanol treatment as seen by 24%, 26%, and 59% lower plasma (p < 0.02), muscle (p < 0.001) and adipose tissue (p < 0.001) {¹⁴C}-D₃ concentrations in ethanol-treated compared to control rats. In contrast total plasma and liver {¹⁴C}-25(OH)D₃ content were increased by 30% (p < 0.05) and 55% (p < 0.001) respectively. This increased liver and plasma {¹⁴C}-25(OH)D₃ following ethanol treatment was not accompanied by a proportional {¹⁴C}-25(OH)D₃ incorporation into muscle and adipose tissue. These results suggest that during steady state conditions 25(OH)D₃ production is increased during chronic ethanol administration while the body pool in unchanged D₃ is significantly lowered. These results also point out that in the rat plasma 25(OH)D concentrations are not a reliable guide for the determination of vitamin D status during chronic ethanol administration.     

Families of Molecular Hexa- and Trideca-Metallic Vanadium(III) Phosphonates

The synthesis and structural characterization of two families of low-valent vanadium(III) {V₆P₄} and vanadium(III/IV) {V₁₃P₈} phosphonate complexes are reported. Magnetic characterization is reported for representative examples.