Amine Dynamics in Diamine-Appended Mg2(dobpdc) Metal-Organic Frameworks.

Variable-temperature 15N solid-state NMR spectroscopy is used to uncover the dynamics of three diamines appended to the metal-organic framework Mg2(dobpdc) (dobpdc4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate), an important family of CO2 capture materials. The results imply both bound and free amine nitrogen environments exist when diamines are coordinated to the framework open Mg2+ sites. There are rapid exchanges between two nitrogen environments for all three diamines, the rates and energetics of which are quantified by 15N solid-state NMR data and corroborated by density functional theory calculations and molecular dynamics simulations. The activation energy for the exchange provides a measure of the metal-amine bond strength. The unexpected negative correlation between the metal-amine bond strength and CO2 adsorption step pressure reveals that metal-amine bond strength is not the only important factor in determining the CO2 adsorption properties of diamine-appended Mg2(dobpdc) metal-organic frameworks

Glassy Dynamics of Protein Methyl Groups Revealed by Deuteron NMR

We investigated site-specific dynamics of key methyl groups in the hydrophobic core of chicken villin headpiece subdomain (HP36) over the temperature range between 298 and 140 K using deuteron solid-state NMR longitudinal relaxation measurements. The relaxation of the longitudinal magnetization is weakly nonexponential (glassy) at high temperatures and exhibits a stronger degree of nonexponentiality below about 175 K. In addition, the characteristic relaxation times deviate from the simple Arrhenius law. We interpret this behavior via the existence of distribution of activation energy barriers for the three-site methyl jumps, which originates from somewhat different methyl environments within the local energy landscape. The width of the distribution of the activation barriers for methyl jumps is rather significant, about 1.4 kJ/mol. Our experimental results and modeling allow for the description of the apparent change at about 175 K without invoking a specific transition temperature. For most residues in the core, the relaxation behavior at high temperatures points to the existence of conformational exchange between the substates of the landscape, and our model takes into account the kinetics of this process. The observed dynamics are the same for dry and hydrated protein. We also looked at the effect of F58L mutation inside the hydrophobic core on the dynamics of one of the residues and observed a significant increase in its conformational exchange rate constant at high temperatures

Fast Motions of Key Methyl Groups in Amyloid-beta Fibrils

Amyloid-beta (A beta) peptide is the major component of plaques found in Alzheimer\u27s disease patients. Using solid-state H-2 NMR relaxation performed on selectively deuterated methyl groups, we probed the dynamics in the threefold symmetric and twofold symmetric polymorphs of native A beta as well as the protofibrils of the D23N mutant. Specifically, we investigated the methyl groups of two leucine residues that belong to the hydrophobic core (L17 and L34) as well as M35 residues belonging to the hydrophobic interface between the cross-beta subunits, which has been previously found to be water-accessible. Relaxation measurements performed over 310-140 K and two magnetic field strengths provide insights into conformational variability within and between polymorphs. Core packing variations within a single polymorph are similar to what is observed for globular proteins for the core residues, whereas M35 exhibits a larger degree of variability. M35 site is also shown to undergo a solvent dependent dynamical transition in which slower amplitude motions of methyl axes are activated at high temperature. The motions, modeled as a diffusion of methyl axis, have activation energy by a factor of 2.7 larger in the twofold compared with the threefold polymorph, whereas D23N protofibrils display a value similar to the threefold polymorph. This suggests enhanced flexibility of the hydrophobic interface in the threefold polymorph. This difference is only observed in the hydrated state and is absent in the dry fibrils, highlighting the role of solvent at the cavity. In contrast, the dynamic behavior of the core is hydration-independent

Dynamics of Hydrophobic Core Phenylalanine Residues Probed by Solid-State Deuteron NMR

We conducted a detailed investigation of the dynamics of two phenylalanine side chains in the hydrophobic core of the villin headpiece subdomain protein (HP36) in the hydrated powder state over the 298-80 K temperature range. Our main tools were static deuteron NMR measurements of longitudinal relaxation and line shapes supplemented with computational modeling. The temperature dependence of the relaxation times reveals the presence of two main mechanisms that can be attributed to the ring-flips, dominating at high temperatures, and small-angle fluctuations, dominating at low temperatures. The relaxation is nonexponential at all temperatures with the extent of nonexponentiality increasing from higher to lower temperatures. This behavior suggests a distribution of conformers with unique values of activation energies. The central values of the activation energies for the ring-flipping motions are among the smallest reported for aromatic residues in peptides and proteins and point to a very mobile hydrophobic core. The analysis of the widths of the distributions, in combination with the earlier results on the dynamics of flanking methyl groups (Vugmeyster et al. J. Phys. Chem. B 2013, 117, 6129-6137), suggests that the hydrophobic core undergoes slow concerted fluctuations. There is a pronounced effect of dehydration on the ring-flipping motions, which shifts the distribution toward more rigid conformers. The crossover temperature between the regions of dominance of the small-angle fluctuations and ring-flips shifts from 195 K in the hydrated protein to 278 K in the dry one. This result points to the role of solvent in softening the core and highlights aromatic residues as markers of the protein dynamical transitions

The Aguablanca Ni–(Cu) sulfide deposit, SW Spain: geologic and geochemical controls and the relationship with a midcrustal layered mafic complex

The Aguablanca Ni–(Cu) sulfide deposit is hosted by a breccia pipe within a gabbro–diorite pluton. The deposit probably formed due to the disruption of a partially crystallized layered mafic complex at about 12– 19 km depth and the subsequent emplacement of melts and breccias at shallow levels (<2 km). The ore-hosting breccias are interpreted as fragments of an ultramafic cumulate, which were transported to the near surface along with a molten sulfide melt. Phlogopite Ar–Ar ages are 341– 332 Ma in the breccia pipe, and 338–334 Ma in the layered mafic complex, and are similar to recently reported U–Pb ages of the host Aguablanca Stock and other nearby calcalkaline metaluminous intrusions (ca. 350–330 Ma). Ore deposition resulted from the combination of two critical factors, the emplacement of a layered mafic complex deep in the continental crust and the development of small dilational structures along transcrustal strike-slip faults that triggered the forceful intrusion of magmas to shallow levels. The emplacement of basaltic magmas in the lower middle crust was accompanied by major interaction with the host rocks, immiscibility of a sulfide melt, and the formation of a magma chamber with ultramafic cumulates and sulfide melt at the bottom and a vertically zoned mafic to intermediate magmas above. Dismembered bodies of mafic/ultramafic rocks thought to be parts of the complex crop out about 50 km southwest of the deposit in a tectonically uplifted block (Cortegana Igneous Complex, Aracena Massif). Reactivation of Variscan structures that merged at the depth of the mafic complex led to sequential extraction of melts, cumulates, and sulfide magma. Lithogeochemistry and Sr and Nd isotope data of the Aguablanca Stock reflect the mixing from two distinct reservoirs, i.e., an evolved siliciclastic middle-upper continental crust and a primitive tholeiitic melt. Crustal contamination in the deep magma chamber was so intense that orthopyroxene replaced olivine as the main mineral phase controlling the early fractional crystallization of the melt. Geochemical evidence includes enrichment in SiO2 and incompatible elements, and Sr and Nd isotope compositions (87Sr/86Sri 0.708–0.710; 143Nd/144Ndi 0.512–0.513). However, rocks of the Cortegana Igneous Complex have low initial 87Sr/86Sr and high initial 143Nd/144Nd values suggesting contamination by lower crustal rocks. Comparison of the geochemical and geological features of igneous rocks in the Aguablanca deposit and the Cortegana Igneous Complex indicates that, although probably part of the same magmatic system, they are rather different and the rocks of the Cortegana Igneous Complex were not the direct source of the Aguablanca deposit. Crust–magma interaction was a complex process, and the generation of orebodies was controlled by local but highly variable factors. The model for the formation of the Aguablanca deposit presented in this study implies that dense sulfide melts can effectively travel long distances through the continental crust and that dilational zones within compressional belts can effectively focus such melt transport into shallow environments

PRISM (Program of Resources, Information and Support for Mothers): a community-randomised trial to reduce depression and improve women's physical health six months after birth [ISRCTN03464021]

BACKGROUND: In the year after birth one in six women has a depressive illness, 94% experience at least one major health problem (e.g. back pain, perineal pain, mastitis, urinary or faecal incontinence), 26% experience sexual problems and almost 20% have relationship problems with partners. Women with depression report less practical and emotional support from partners, less social support, more negative life events, and poorer physical health and see factors contributing to depression as lack of support, isolation, exhaustion and physical health problems. Fewer than one in three seek help in primary care despite frequent health care contacts. METHODS: Primary care and community-based strategies embedded in existing services were implemented in a cluster-randomised trial involving 16 rural and metropolitan communities, pair-matched, within the State of Victoria, Australia. Intervention areas were also provided with a community development officer for two years. The primary aim was to reduce the relative risk of depression by 20% in mothers six months after birth and to improve their physical health. Primary outcomes were obtained by postal questionnaires. The analysis was by intention-to-treat, unmatched, adjusting for the correlated nature of the data. RESULTS: 6,248 of 10,144 women (61.6%) in the intervention arm and 5057/ 8,411 (60.1%) in the comparison arm responded at six months, and there was no imbalance in major covariates between the two arms. Women's mental health scores were not significantly different in the intervention arm and the comparison arm (MCS mean score 45.98 and 46.30, mean EPDS score 6.91 and 6.82, EPDS ≥ 13 ('probable depression') 15.7% vs. 14.9%, Odds ratio(adj )1.06 (95%CI 0.91–1.24). Women's physical health scores were not significantly different in intervention and comparison arms (PCS mean scores 52.86 and 52.88). CONCLUSION: The combined community and primary care interventions were not effective in reducing depression, or in improving the physical health of mothers six months after birth