Molecular Mechanics Studies of Molybdenum Disulphide Catalysts Parameterisation of Molybdenum and Sulphur

Abstract

A method for the parameterisation of molybdenum disulphide is presented which reproduces the crystal structure accurately. The method involves calculating parameters such that there is no net force contribution from any individual term of the potential on any atom. Ideal bond lengths and bond angles are taken from the X-ray crystal structure; stretching and bending force constants are calculated from a combination of spectroscopic data and quantum mechanics calculations, whereby the energy function with bond length or bond angle is calculated and fitted with an harmonic potential. For the non-bonded Lennard-Jones parameters, the dispersion coefficient C was calculated by an interpolation of existing published parameters using a multiple regression and then the crystal energy was minimised with respect to the van der Waals radius r₀ using a fixed crystal fragment.

These parameters were tested for various models of the hexagonal and rhombohedral forms of MoS₂. RMS fits between structures minimised with molecular mechanics and experimental models ranged from 0.006 Å to 0.012 Å.     

A Flow Sensing Model for Mesenchymal Stromal Cells Using Morphogen Dynamics

The differentiation of mesenchymal stromal cells has been shown to be affected by many parameters such as morphogens, flow rate, medium viscosity, and shear stress when exposed to fluid flow. The mechanism by which these cells sense their environment is still under intense discussion. In particular, during flow chamber experiments, it is difficult to interpret the interplay of the above-mentioned parameters in the process of cell differentiation. In this work, we tested the hypothesis that the competition between diffusion and advection of paracrine morphogens could explain the dependency of the cell differentiation to the above-mentioned parameters. To evaluate this hypothesis, we developed a numerical model simulating a simplified version of the advection-diffusion-reaction of morphogens secreted by the cells within a flow chamber. The model predicted a sharp transition in the fraction of receptors bound to the morphogen. This transition was characterized by a new, dimensionless number depending on flow rate, flow viscosity, flow chamber dimensions, and morphogen decay rate. We concluded that the competition between diffusion and advection of paracrine morphogens can act as a probe for the cells to sense their pericellular environment.     

Fungal siderophore biosynthesis is partially localized in peroxisomes

Siderophores play a central role in iron metabolism and virulence of most fungi. Both Aspergillus fumigatus and Aspergillus nidulans excrete the siderophore triacetylfusarinine C (TAFC) for iron acquisition. In A. fumigatus, green fluorescence protein‐tagging revealed peroxisomal localization of the TAFC biosynthetic enzymes SidI (mevalonyl‐CoA ligase), SidH (mevalonyl‐CoA hydratase) and SidF (anhydromevalonyl‐CoA transferase), while elimination of the peroxisomal targeting signal (PTS) impaired both, peroxisomal SidH‐targeting and TAFC biosynthesis. The analysis of A. nidulans mutants deficient in peroxisomal biogenesis, ATP import or protein import revealed that cytosolic mislocalization of one or two but, interestingly, not all three enzymes impairs TAFC production during iron starvation. The PTS motifs are conserved in fungal orthologues of SidF, SidH and SidI. In agreement with the evolutionary conservation of the partial peroxisomal compartmentalization of fungal siderophore biosynthesis, the SidI orthologue of coprogen‐type siderophore‐producing Neurospora crassa was confirmed to be peroxisomal. Taken together, this study identified and characterized a novel, evolutionary conserved metabolic function of peroxisomes.     

Copper complexing capacity in fresh-waters using the catechol-cathodic stripping voltammetric method

Abstract

The catechol-cathodic stripping voltammetric (CSV) method for measurement of the copper complexing capacity of marine and estuarine waters, has been modified and applied to fresh-waters. The optimum catechol concentration needed was the major difference between the two methods. It was found necessary to separately optimise the catechol concentration for each of the three fresh-water samples tested, presumably because of the much greater differences in the concentration of complexing ligands in fresh-water compared with marine or estuarine waters. This limits the usefulness of the CSV method for the determination of the complexing capacity of fresh-waters.

The total ligand concentration ([L_t]) and conditional stability constants (*K) derived for the three fresh-waters are compared with similar data obtained using an anodic stripping voltammetric (ASV) method. The set of copper-binding ligands determined using the CSV method were slightly lower in concentration, but stronger binding, than those obtained using the ASV method (CSV: [L_t] 0.04–0.06 μM, log K(pH 6) 8.9–9.4; ASV: [L_t] 0.11–0.17 μM, log *K(pH 6) 7.9–8.1).     

Synthesis and evaluation of carbamoylmethylene linked prodrugs of BMS-582949, a clinical p38α inhibitor

A series of carbamoylmethylene linked prodrugs of 1 (BMS-582949), a clinical p38α inhibitor, were synthesized and evaluated. Though the phosphoryloxymethylene carbamates (3, 4, and 5) and α-aminoacyloxymethylene carbamates (22, 23, and 26) were found unstable at neutral pH values, fumaric acid derived acyloxymethylene carbamates (2, 28, and 31) were highly stable under both acidic and neutral conditions. Prodrugs 2 and 31 were also highly soluble at both acidic and neutral pH values. At a solution dose of 14.2 mpk (equivalent to 10 mpk of 1), 2 gave essentially the same exposure of 1 compared to dosing 10 mpk of 1 itself. At a suspension dose of 142 mpk (equivalent to 100 mpk of 1), 2 demonstrated that it could overcome the solubility issue associated with 1 and provide a much higher exposure of 1. To our knowledge, the unique type of prodrugs like 2, 28, and 31 was not reported in the past and could represent a novel prodrug approach for secondary amides, a class of molecules frequently identified as drug candidates.     

A Systematic Review of the Relationships between Intimate Partner Violence and HIV/AIDS

Background

Intimate partner violence (IPV) is a significant health problem that has been associated with HIV infection in numerous studies. We aimed to systematically review the literature on relationships between IPV and HIV in order to describe the prevalence of IPV in people with HIV, the prevalence of HIV in people experiencing IPV, the association between IPV and HIV, and evidence regarding mechanisms of risk and interventions.

Methods

Data sources were 10 electronic databases and reference lists. Studies were included if they reported data on the relationship between IPV and HIV. All records were independently reviewed by two authors at the stages of title and abstract review and full text review. Any abstract considered eligible by either reviewer was reviewed in full, and any disagreement regarding eligibility of full texts or data extracted was resolved by discussion.

Results

101 articles were included. Experiencing IPV and HIV infection were associated in unadjusted analyses in most studies, as well as in adjusted analyses in many studies. The findings of qualitative and quantitative studies assessing potential mechanisms linking IPV and HIV were variable. Few interventions have been assessed, but two identified in this review were promising in terms of preventing IPV, though not HIV infection.

Conclusions

Experiencing IPV and HIV infection tend to be associated in unadjusted analyses, suggesting that IPV screening and linkage with relevant programs and services may be valuable. It is unclear whether there is a causal association between experiencing IPV and HIV infection. Research should focus on defining parameters of IPV which are relevant to HIV infection, including type of IPV and period of exposure and risk, on assessing potential mechanisms, and on developing and assessing interventions which build on the strengths of existing studies.