Lysyl hydroxylase 3 localizes to epidermal basement membrane and Is reduced in patients with Recessive Dystrophic Epidermolysis Bullosa

Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in COL7A1 resulting in reduced or absent type VII collagen, aberrant anchoring fibril formation and subsequent dermal-epidermal fragility. Here, we identify a significant decrease in PLOD3 expression and its encoded protein, the collagen modifying enzyme lysyl hydroxylase 3 (LH3), in RDEB. We show abundant LH3 localising to the basement membrane in normal skin which is severely depleted in RDEB patient skin. We demonstrate expression is in-part regulated by endogenous type VII collagen and that, in agreement with previous studies, even small reductions in LH3 expression lead to significantly less secreted LH3 protein. Exogenous type VII collagen did not alter LH3 expression in cultured RDEB keratinocytes and we show that RDEB patients receiving bone marrow transplantation who demonstrate significant increase in type VII collagen do not show increased levels of LH3 at the basement membrane. Our data report a direct link between LH3 and endogenous type VII collagen expression concluding that reduction of LH3 at the basement membrane in patients with RDEB will likely have significant implications for disease progression and therapeutic intervention

Theoretical investigation in the structural properties, bonding, and reactivity of some chalcogen compounds

Abstract In this thesis the bonding, structural properties, and chemical reaction pathways have been investigated for several different types of chalcogen-containing molecules. The work encompasses sulfur nitride polymers, metal complexes of selenium diimides, organic disulfide nitrosonium adducts and chalcogenidoborate anions. Novel work on the explanation of the polymerization pathways of the disulfur dinitride ring presents the first example of a molecular dynamics simulation study on a topochemical reaction in the field of inorganic chemistry. Structural and bonding analysis of dinuclear copper(I) and silver(I) selenium diimides has been carried out to investigate the d10-d10 closed-shell interactions with the Atoms in Molecules theory. Molecular orbital analysis of organic disulfide nitrosonium adducts show a clear and chemically intuitive reaction mechanism. Stabilities of yet unknown adducts have also been considered. The possibility to prepare hitherto unknown hybrid chalcogenidoborates has been explored by theoretical methods. The trends in their structures and bonding have also been discussed

Molecular Dynamics Simulation of the Solid-State Topochemical Polymerization of S₂N₂

Molecular dynamics simulations of the solid-state topochemical polymerization of four-membered S₂N₂ rings to (SN)_<i>x</i> have been presented by involving DFT methods and periodic functions. Isotropic pressure compression and a slightly elevated temperature have been applied to lower the activation barriers and to increase the rate of the reaction to be within the framework of MD simulations. The polymer formation is initiated by the cleavage of one bond in one S₂N₂ ring with a virtually instantaneous attack of the fragment thus formed on the neighboring ring. The energetically most-favored reaction then quickly propagates along <i>a</i> axis throughout the lattice. The structures of the polymer chains are in good agreement with that observed experimentally in the crystal structure determination, but there is less long-range order between the neighboring chains. Upon polymerization the packing of the molecules changes from the herringbone structure of the S₂N₂ lattice to a layered structure in the (SN)_<i>x</i> lattice. While not the same, the simulated and experimental packing changes bear a qualitative similarity. The simulated polymerization was also observed to propagate along <i>c</i> axis in addition to <i>a</i> axis, but these side effects generally disappear toward the end of the simulations. In some cases, the polymers propagating simultaneously in both <i>a</i> and <i>c</i> axis directions persist at the end of the simulation resulting in a complicated network of sulfur–nitrogen chains. This finds experimental support in the observation of several polymorphs (SN)_<i>x</i> with severe disorder in the lattice

Ammonium removal by metakaolin-based geopolymers from municipal and industrial wastewaters and its sequential recovery by stripping techniques

Abstract In this study, a technical scheme of an ammonium recovery process from diluted municipal or industrial wastewaters was developed, and the main operational parameters of adsorption/desorption and air-stripping/acid-scrubbing or membrane units were examined. The proposed approach combines the removal of ammonium nitrogen by an ion-exchange mechanism on metakaolin-based geopolymers (MKGPs) followed by adsorbent regeneration. A regeneration agent was purified by the air-stripping technique or membrane technology. A ready-to-use market-grade fertilizer or industrial-grade ammonia water could be obtained as the final product. The properties and regeneration ability of MKGP, prepared from activated kaolinite clay, were compared with new geopolymer adsorbents based on papermill sludge (FS MKGP). Adsorption fixed-bed column experiments with continuously circulated regeneration solution purified by air-stripping or the membrane approach were conducted to determine the limits of the regeneration solution’s application. Sodium and potassium salts were tested as regeneration agents, and the influence of regeneration solution composition on ammonium removal and recovery rates was investigated. Based on a breakthrough curve analysis, the removal rate of ammonium N by FS MKGP was found to be 3.2 times higher than that by MKGP for actual wastewater samples. Moreover, there were substantial differences in the regeneration regime between the two adsorbents. For the air-stripping technique, a liquid-phase temperature of 45°C was minimal and enough for efficient ammonia transfer to the gaseous phase. For the membrane technique, a feed-phase temperature of 40°C was enough for removing ammonia from the regeneration solution, while no heating of a receiving phase was required

In situ remediation of metal(loid)-contaminated lake sediments with alkali-activated blast furnace slag granule amendment:a field experiment

Abstract Purpose: Adsorbent amendment to contaminated sediments is one in situ remediation method to decrease the bioaccessibility of pollutants from the sediments. In this work, alkali-activated blast furnace slag (BFS) granules were used in a field experiment at Lake Kivijärvi (Finland). The lake was heavily affected by a mining accident in 2012, which released a significant peak load of metals and sulfate. The purpose of this work was to evaluate the performance of the novel amendment material for in situ remediation in real conditions with a preliminary cost estimation. Methods: Alkali-activated BFS granules were prepared and characterized for composition, microstructure, and surface properties. Two mesocosms were placed in the lake: one with granule dosing and another without. Sediment and pore water samples were collected after a two-week period. Similar small-scale experiment was performed in laboratory with a three-month duration. Bioaccessibility of metals from sediments was assessed with a three-stage leaching procedure. Results: The granules were effective in decreasing the mobility of Fe, Zn, Ni, and Cr in all leaching stages by approximately 50–90% in comparison with unamended sediment in the mesocosm experiment. Laboratory-scale incubation experiments also indicated decreased release of Ba, Co, Ni, Al, Fe, Mg, Mn and S. The estimated material costs were lower than the removal of the contaminated sediments with dredging and off-site treatment. Conclusion: The results showed preliminarily the effectiveness of alkaline-activated BFS in the remediation of metal-contaminated sediments in a field experiment. However, topics requiring further study are the leaching of trace elements from the material and impact on the sediment pH

Theoretical and Synthetic Study on the Existence, Structures, and Bonding of the Halide-Bridged [B₂X₇]⁻ (X = F, Cl, Br, I) Anions

While hydrogen bridging is very common in boron chemistry, halogen bridging is rather rare. The simplest halogen-bridged boron compounds are the [B₂X₇]⁻ anions (X = F, Cl, Br, I), of which only [B₂F₇]⁻ has been reported to exist experimentally. In this paper a detailed theoretical and synthetic study on the [B₂X₇]⁻ anions is presented. The structures of [B₂X₇]⁻ anions have been calculated at the MP2/def2-TZVPP level of theory, and their local minima have been shown to be of <i>C</i>₂ symmetry in all cases. The bonding situation varies significantly between the different anions. While in [B₂F₇]⁻ the bonding is mainly governed by electrostatics, the charge is almost equally distributed over all atoms in [B₂I₇]⁻ and additional weak iodine···iodine interactions are observed. This was shown by an atoms in molecules (AIM) analysis. The thermodynamic stability of the [B₂X₇]⁻ anions was estimated in all phases (gas, solution, and solid state) based on quantum-chemical calculations and estimations of the lattice enthalpies using a volume-based approach. In the gas phase the formation of [B₂X₇]⁻ anions from [BX₄]⁻ and BX₃ is favored in accord with the high Lewis acidity of the BX₃ molecules. In solution and in the solid state only [B₂F₇]⁻ is stable against dissociation. The other three anions are borderline cases, which might be detectable under favorable conditions. However, experimental attempts to identify [B₂X₇]⁻ (X = Cl, Br, I) anions in solution by ¹¹B NMR spectroscopy and to prepare stable [PNP]­[B₂X₇] salts failed

Perovskite Quantum Dots Modeled Using ab Initio and Replica Exchange Molecular Dynamics

Organometal halide perovskites have recently attracted tremendous attention at both the experimental and theoretical levels. Much of this work has been dedicated to bulk material studies, yet recent experimental work has shown the formation of highly efficient quantum-confined nanocrystals with tunable band edges. Here we investigate perovskite quantum dots from theory, predicting an upper bound of the Bohr radius of 45 Å that agrees well with literature values. When the quantum dots are stoichiometric, they are trap-free and have nearly symmetric contributions to confinement from the valence and conduction bands. We further show that surface-associated conduction bandedge states in perovskite nanocrystals lie below the bulk states, which could explain the difference in Urbach tails between mesoporous and planar perovskite films. In addition to conventional molecular dynamics (MD), we implement an enhanced phase-space sampling algorithm, replica exchange molecular dynamics (REMD). We find that in simulation of methylammonium orientation and global minima, REMD outperforms conventional MD. To the best of our knowledge, this is the first REMD implementation for realistic-sized systems in the realm of DFT calculations

FKBP65-dependent peptidyl-prolyl isomerase activity potentiates the lysyl hydroxylase 2-driven collagen cross-link switch

Bruck Syndrome is a connective tissue disease associated with inactivating mutations in lysyl hydroxylase 2 (LH2/PLOD2) or FK506 binding protein 65 (FKBP65/FKBP10). However, the functional relationship between LH2 and FKBP65 remains unclear. Here, we postulated that peptidyl prolyl isomerase (PPIase) activity of FKBP65 positively modulates LH2 enzymatic activity and is critical for the formation of hydroxylysine-aldehyde derived intermolecular collagen cross-links (HLCCs). To test this hypothesis, we analyzed collagen cross-links in Fkbp10-null and –wild-type murine embryonic fibroblasts. Although LH2 protein levels did not change, FKBP65 deficiency significantly diminished HLCCs and increased the non-hydroxylated lysine-aldehyde–derived collagen cross-links (LCCs), a pattern consistent with loss of LH2 enzymatic activity. The HLCC-to-LCC ratio was rescued in FKBP65-deficient murine embryonic fibroblasts by reconstitution with wild-type but not mutant FKBP65 that lacks intact PPIase domains. Findings from co-immunoprecipitation, protein-fragment complementation, and co-immunofluorescence assays showed that LH2 and FKBP65 are part of a common protein complex. We conclude that FKBP65 regulates LH2-mediated collagen cross-linking. Because LH2 promotes fibrosis and cancer metastasis, our findings suggest that pharmacologic strategies to target FKBP65 and LH2 may have complementary therapeutic activities