Mineral–water reactions in Earth’s mantle:Predictions from Born theory and ab initio molecular dynamics

Recent studies present compelling evidence that a free aqueous fluid phase exists within the upper mantle. Fluid may be present at depths as great as the transition zone (410–660 km) and possibly beyond. The chemical reactivity of such deep fluids can be predicted from the Born model of solvation. To use the Born model, we need to know the dielectric constant of water under mantle conditions. We have used ab initio molecular dynamics simulations to determine the dielectric constant of water up to a pressure of 30 GPa and a temperature of 3000 K. Increased temperature lowers the dielectric constant and decreases ion solvation, but pressure overcomes this effect. The resulting high dielectric constant suggests that aqueous mantle fluids are highly reactive for ion solvation and mineral dissolution. We tested this by using the Helgeson–Kirkham–Flowers equation of state to estimate free energies of several mineral-solution and ion solvation reactions under mantle conditions. The results support previous estimates of carbonate solubility in the mantle. We also find that mantle fluids may play a key role in transporting ore metals: we evaluated the solubility of chalcopyrite and the complexation of Cu and Fe by Cl under mantle conditions and find that metal complexation is as significant as in ore-forming fluids in the crust. At reasonable conditions of pH and fH2, chalcopyrite is highly soluble. We tentatively hypothesize that exsolved fluids from subducted slabs may extract and mobilize primary sulfides in the mantle, implying potentially deep sources for porphyry copper deposits

Insights into the structural nature of the transition state in the Kir channel gating pathway

YesIn a previous study we identified an extensive gating network within the inwardly rectifying Kir1.1 (ROMK) channel by combining systematic scanning mutagenesis and functional analysis with structural models of the channel in the closed, pre-open and open states. This extensive network appeared to stabilize the open and pre-open states, but the network fragmented upon channel closure. In this study we have analyzed the gating kinetics of different mutations within key parts of this gating network. These results suggest that the structure of the transition state (TS), which connects the pre-open and closed states of the channel, more closely resembles the structure of the pre-open state. Furthermore, the G-loop, which occurs at the center of this extensive gating network, appears to become unstructured in the TS because mutations within this region have a 'catalytic' effect upon the channel gating kinetics.Deutsche Forschungsgemeinschaft, the Wellcome Trust (083547/ Z/07/Z and 092970/Z/10/Z) and the British Heart Foundation (PG/09/016/ 26992)

Convexity deficit of benzenoids

In 2012, a family of benzenoids was introduced by Cruz, Gutman, and Rada, which they called convex benzenoids. In this paper we introduce the convexity deficit, a new topological index intended for benzenoids and, more generally, fusenes. This index measures by how much a given fusene departs from convexity. It is defined in terms of the boundary-edges code. In particular, convex benzenoids are exactly the benzenoids having convexity deficit equal to 0. Quasi-convex benzenoids form the family of non-convex benzenoids that are closest to convex, i.e., they have convexity deficit equal to 1. Finally, we investigate convexity deficit of several important families of benzenoids

Ferroan dolomitization by seawater interaction with mafic igneous dikes and carbonate host rock at the Latemar Platform, Dolomites, Italy: numerical modeling of spatial, temporal, and temperature data

Numerous publications address the petrogenesis of the partially dolomitized Latemar carbonate platform, Italy. A common factor is interpretation of geochemical data in terms of heating via regional igneous activity that provided kinetically favorable conditions for replacement dolomitization. New field, petrographic, XRD, and geochemical data demonstrate a spatial, temporal, and geochemical link between replacement dolomite and local mafic igneous dikes that pervasively intrude the platform. Dikes are dominated by strongly altered plagioclase and clinopyroxene. Significantly, where ferroan dolomite is present, it borders dikes. We hypothesize that seawater interacted with mafic minerals, causing Fe enrichment in the fluid that subsequently participated in dolomitization. This hypothesis was tested numerically through thermodynamic (MELTS, Arxim-GEM) and reactive flow (Arxim-LMA) simulations. Results confirm that seawater becomes Fe-enriched during interaction with clinopyroxene (diopside-hedenbergite) and plagioclase (anorthite-albite-orthoclase) solid solutions. Reaction of modified seawater with limestone causes ferroan and nonferroan replacement dolomitization. Dolomite quantities are strongly influenced by temperature. At 40 to 80 degrees C, ferroan dolomite proportions decrease with increasing temperature, indicating that Latemar dolomitization likely occurred at lower temperatures. This relationship between igneous dikes and dolomitization may have general significance due to the widespread association of carbonates with rifting-related igneous environments

Quantum magneto-oscillations in a two-dimensional Fermi liquid

Quantum magneto-oscillations provide a powerfull tool for quantifying Fermi-liquid parameters of metals. In particular, the quasiparticle effective mass and spin susceptibility are extracted from the experiment using the Lifshitz-Kosevich formula, derived under the assumption that the properties of the system in a non-zero magnetic field are determined uniquely by the zero-field Fermi-liquid state. This assumption is valid in 3D but, generally speaking, erroneous in 2D where the Lifshitz-Kosevich formula may be applied only if the oscillations are strongly damped by thermal smearing and disorder. In this work, the effects of interactions and disorder on the amplitude of magneto-oscillations in 2D are studied. It is found that the effective mass diverges logarithmically with decreasing temperature signaling a deviation from the Fermi-liquid behavior. It is also shown that the quasiparticle lifetime due to inelastic interactions does not enter the oscillation amplitude, although these interactions do renormalize the effective mass. This result provides a generalization of the Fowler-Prange theorem formulated originally for the electron-phonon interaction.Comment: 4 pages, 1 figur

Core Alzheimer’s disease cerebrospinal fluid biomarker assays are not affected by aspiration or gravity drip extraction methods

Background CSF biomarkers are well-established for routine clinical use, yet a paucity of comparative assessment exists regarding CSF extraction methods during lumbar puncture. Here, we compare in detail biomarker profiles in CSF extracted using either gravity drip or aspiration. Methods Biomarkers for β-amyloidopathy (Aβ1–42, Aβ1–40), tauopathy (total tau), or synapse pathology (BACE1, Neurogranin Trunc-p75, α-synuclein) were assessed between gravity or aspiration extraction methods in a sub-population of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study (cognitively normal, N = 36; mild cognitive impairment, N = 8; Alzheimer’s disease, N = 6). Results High biomarker concordance between extraction methods was seen (concordance correlation > 0.85). Passing Bablock regression defined low beta coefficients indicating high scalability. Conclusions Levels of these commonly assessed CSF biomarkers are not influenced by extraction method. Results of this study should be incorporated into new consensus guidelines for CSF collection, storage, and analysis of biomarkers

hERG Blockade by Iboga Alkaloids

The iboga alkaloids are a class of naturally occurring and synthetic compounds, some of which modify drug self-administration and withdrawal in humans and preclinical models. Ibogaine, the prototypic iboga alkaloid that is utilized clinically to treat addictions, has been associated with QT prolongation, torsades de pointes and fatalities. hERG blockade as IKr was measured using the whole-cell patch clamp technique in HEK 293 cells. This yielded the following IC50 values: ibogaine manufactured by semisynthesis via voacangine (4.09 ± 0.69 µM) or by extraction from T. iboga (3.53 ± 0.16 µM); ibogaine’s principal metabolite noribogaine (2.86 ± 0.68 µM); and voacangine (2.25 ± 0.34 µM). In contrast, the IC50 of 18-methoxycoronaridine, a product of rational synthesis and current focus of drug development was >50 µM. hERG blockade was voltage dependent for all of the compounds, consistent with low-affinity blockade. hERG channel binding affinities (Ki) for the entire set of compounds, including 18-MC, ranged from 0.71 to 3.89 µM, suggesting that 18-MC binds to the hERG channel with affinity similar to the other compounds, but the interaction produces substantially less hERG blockade. In view of the extended half-life of noribogaine, these results may relate to observations of persistent QT prolongation and cardiac arrhythmia at delayed intervals of days following ibogaine ingestion. The apparent structure–activity relationships regarding positions of substitutions on the ibogamine skeleton suggest that the iboga alkaloids might provide an informative paradigm for investigation of the structural biology of the hERG channel

Pregnancy in women with perinatally acquired HIV-infection: Outcomes and challenges

This is a retrospective comparison of pregnant women with perinatally acquired HIV-infection (PAH) with a cohort of pregnant women with behaviorally acquired HIV-infection (BAH). PAH cases (11 women) included all pregnant adolescents followed at our HIV clinic from January 2000 to January 2009. BAH cases (27 women) were randomly selected from all deliveries within the study period at the same institution. Demographics, mode of delivery, CD4+ counts, and viral loads (VLs) before, during, and six months postpartum, as well as neonatal outcomes, were reviewed

The β3-integrin endothelial adhesome regulates microtubule-dependent cell migration

Integrin β3 is seen as a key anti-angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro- or anti-angiogenic depends on the context in which it is expressed. To understand precisely β3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the β3-dependent adhesome. We show that depletion of β3-integrin in this cell type leads to changes in microtubule behaviour that control cell migration. β3-integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2-driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when β3-integrin levels are reduced

Using process algebra to model radiation induced bystander effects

Radiation induced bystander effects are secondary effects caused by the production of chemical signals by cells in response to radiation. We present a Bio-PEPA model which builds on previous modelling work in this field to predict: the surviving fraction of cells in response to radiation, the relative proportion of cell death caused by bystander signalling, the risk of non-lethal damage and the probability of observing bystander signalling for a given dose. This work provides the foundation for modelling bystander effects caused by biologically realistic dose distributions, with implications for cancer therapies