КВАНТОВО-ХИМИЧЕСКОЕ ОБОСНОВАНИЕ СВОЙСТВ БИОРЕАГЕНТА, ОКИСЛЯЮЩЕГО СУЛЬФИДЫ ЦВЕТНЫХ МЕТАЛЛОВ

The paper determines the structural formula and quantum chemical characteristics of the most energetically probable, stable conformation of the bioreagent molecule formed during the oxidation of iron (II) ions by the autotrophic mesophilic iron-oxidizing bacteria Acidithiobacillus ferrooxidans in a solution of sulfuric acid consisting of iron (III) ion and three acid residues of glucuronic acid.The bioreagent oxidant is widely used in the industry for leaching metals from non-ferrous sulfide ores and enrichment concentrates.The quantum chemical characteristics of the bioreagent molecule are analyzed in comparison with the characteristics of anhydrous iron (III) sulphate, also used in hydrometallurgy as an oxidizer. The structure and quantum-chemical characteristics are studied using the method of molecular computer simulation, the theory of boundary molecular orbitals, and the Pearson principle. It has been established that the most energetically probable, stable conformation of the bioreagent molecule contains the acid residues of glucuronic acid of a non-cyclic structure. According to the research results, the bioreagent refers to the more rigid Lewis acid – electron acceptor – than iron (III) sulphate. The bioreagent molecule is less polarized, characterized by lower absolute electronegativity and 2 times larger volume. A theoretical substantiation of the greater persistence of primary sulphides – pyrite, pentlandite, chalcopyrite, relative to the secondary minerals – pyrrhotine, chalcocite and covellite is proposed based on the calculated values of the boundary molecular orbitals, absolute stiffness and electronegativity of iron, copper and nickel sulfides. The bioreagent characteristics that determine the interaction efficiency – volume, heat of formation, steric energy and its components, total energy, etc. are many times greater than for Fe2(SO4)3. The high oxidative activity of the bioreagent relative to Fe2(SO4)3 can be justified by the higher partial charge of the iron atom, the greater length of bonds between atoms, the lower energy of the lower free molecular orbitals and the greater degree of charge transfer during the interaction of the bioreagent with the sulfide minerals.Определены структурная формула и квантово-химические характеристики наиболее энергетически вероятной, устойчивой конформации молекулы биореагента, образуемого при окислении ионов железа (II) автотрофными мезофильными железоокисляющими бактериями Acidithiobacillus ferrooxidans в растворе серной кислоты, состоящего из иона железа (III) и трех кислотных остатков глюкуроновой кислоты. Биореагент-окислитель широко применяется в промышленности для выщелачивания металлов из сульфидных руд цветных металлов и концентратов обогащения. Проведен анализ квантово-химических характеристик молекулы биореагента в сравнении с безводным сульфатом железа (III), также используемым в качестве окислителя в гидрометаллургии. Для исследования структуры и квантово-химических характеристик использовались метод молекулярного компьютерного моделирования, теория граничных молекулярных орбиталей и принцип Пирсона. Установлено, что наиболее энергетически вероятная, устойчивая конформация молекулы биореагента содержит кислотные остатки глюкуроновой кислоты нециклической структуры. Согласно результатам исследований биореагент относится к более жесткой кислоте Льюиса (акцептору электронов), чем Fe2(SO4)3. Молекула биореагента менее поляризована и характеризуется меньшей абсолютной электроотрицательностью и в 2 раза бóльшим объемом.По рассчитанным значениям граничных молекулярных орбиталей, абсолютной жесткости и электроотрицательности сульфидов железа, меди и никеля предложено теоретическое обоснование большей упорности первичных сульфидов (пирита, пентландита, халькопирита) относительно вторичных минералов (пирротина, халькозина и ковеллина). Определяющие эффективность взаимодействия характеристики (объем, теплота образования, стерическая энергия и ее составляющие, общая энергия и др.) биореагента во много раз выше, чем у Fe2(SO4)3. Большая окислительная активность биореагента относительно Fe2(SO4)3 может обосновываться бóльшими частичным зарядом атома железа и длиной связей между атомами, меньшей энергией низшей свободной молекулярной орбитали, а также повышенной степенью переноса заряда при взаимодействии биореагента с сульфидными минералами

A dramatic isotope effect in the reaction of ClSiH with trimethylsilane-1-d: experimental evidence for intermediate complexes in silylene Si-H(D) insertion reactions

A kinetic isotope effect (kD/kH) of 7.4 has been found for the reaction of chlorosilylene with trimethysilane (Me3SiD vs Me3SiH). Such a value can be accounted for by theoretical modelling, but only if an internal rearrangement of the initially form complex is included in the mechanism. This provides the first concrete evidence for such complexes

MODERN APPROACH TO MOLECULAR CHARACTERIZATION OF PROSTATE TUMORS

The aim of the study was the development of a cell biosensor system based on the fact that AR activator stimuli lead to redistribution of AR from cytoplasm to the nucleus. These changes could be measured and used for the diagnostics and personalized treatment of prostate cancer patient. The stably transfected cell lines with fluorescently tagged AR were generated. For the stable cell expression the non AR expressing HeLa cell line was used. The constructs of chimeric fluorescent proteins wild type AR or mutant ART877A were used for the transfection. The changes of the CFP-AR-YFP and CFP-ART877A-YFP proteins in the nucleus of HeLa cells under different concentrations steroids treatment was investigated. Moreover, the quantity of activated receptor in the nucleus was carried

Poloxomer 188 Has a Deleterious Effect on Dystrophic Skeletal Muscle Function

Duchenne muscular dystrophy (DMD) is an X-linked, fatal muscle wasting disease for which there is currently no cure and limited palliative treatments. Poloxomer 188 (P188) is a tri-block copolymer that has been proposed as a potential treatment for cardiomyopathy in DMD patients. Despite the reported beneficial effects of P188 on dystrophic cardiac muscle function, the effects of P188 on dystrophic skeletal muscle function are relatively unknown. Mdx mice were injected intraperitoneally with 460 mg/kg or 30 mg/kg P188 dissolved in saline, or saline alone (control). The effect of single-dose and 2-week daily treatment was assessed using a muscle function test on the Tibialis Anterior (TA) muscle in situ in anaesthetised mice. The test comprises a warm up, measurement of the force-frequency relationship and a series of eccentric contractions with a 10% stretch that have previously been shown to cause a drop in maximum force in mdx mice. After 2 weeks of P188 treatment at either 30 or 460 mg/kg/day the drop in maximum force produced following eccentric contractions was significantly greater than that seen in saline treated control mice (P = 0.0001). Two week P188 treatment at either dose did not significantly change the force-frequency relationship or maximum isometric specific force produced by the TA muscle. In conclusion P188 treatment increases susceptibility to contraction-induced injury following eccentric contractions in dystrophic skeletal muscle and hence its suitability as a potential therapeutic for DMD should be reconsidered

Impaired complex I repair causes recessive Leber's hereditary optic neuropathy

Leber's hereditary optic neuropathy (LHON) is the most frequent mitochondrial disease and was the first to be genetically defined by a point mutation in mitochondrial DNA (mtDNA). A molecular diagnosis is achieved in up to 95% of cases, the vast majority of which are accounted for by 3 mutations within mitochondrial complex I subunit-encoding genes in the mtDNA (mtLHON). Here, we resolve the enigma of LHON in the absence of pathogenic mtDNA mutations. We describe biallelic mutations in a nuclear encoded gene, DNAJC30, in 33 unsolved patients from 29 families and establish an autosomal recessive mode of inheritance for LHON (arLHON), which to date has been a prime example of a maternally inherited disorder. Remarkably, all hallmarks of mtLHON were recapitulated, including incomplete penetrance, male predominance, and significant idebenone responsivity. Moreover, by tracking protein turnover in patient-derived cell lines and a DNAJC30-knockout cellular model, we measured reduced turnover of specific complex I N-module subunits and a resultant impairment of complex I function. These results demonstrate that DNAJC30 is a chaperone protein needed for the efficient exchange of complex I subunits exposed to reactive oxygen species and integral to a mitochondrial complex I repair mechanism, thereby providing the first example to our knowledge of a disease resulting from impaired exchange of assembled respiratory chain subunits

Thermal effects of carbonated hydroxyapatite modified by glycine and albumin

In this work calcium phosphate powders were obtained by precipitation method from simulated solutions of synovial fluid containing glycine and albumin. X-ray diffraction and IR spectroscopy determined that all samples are single-phase and are presented by carbonate containing hydroxyapatite (CHA). The thermograms of solid phases of CHA were obtained and analyzed; five stages of transformation in the temperature range of 25-1000°C were marked. It is shown that in this temperature range dehydration, decarboxylation and thermal degradation of amino acid and protein connected to the surface of solid phase occur. The tendency of temperature lowering of the decomposition of powders synthesized from a medium containing organic substances was determined. Results demonstrate a direct dependence between the concentration of the amino acid in a model solution and its content in the solid phase

A β-Catenin-Dependent Wnt Pathway Mediates Anteroposterior Axon Guidance in C. elegans Motor Neurons

Wnts are secreted glycoproteins that regulate diverse aspects of development, including cell proliferation, cell fate specification and differentiation. More recently, Wnts have been shown to direct axon guidance in vertebrates, flies and worms. However, little is known about the intracellular signaling pathways downstream of Wnts in axon guidance.Here we show that the posterior C. elegans Wnt protein LIN-44 repels the axons of the adjacent D-type motor neurons by activating its receptor LIN-17/Frizzled on the neurons. Moreover, mutations in mig-5/Disheveled, gsk-3, pry-1/Axin, bar-1/beta-catenin and pop-1/TCF, also cause disrupted D-type axon pathfinding. Reduced BAR-1/beta-catenin activity in D-type axons leads to undergrowth of axons, while stabilization of BAR-1/beta-catenin in a lin-23/SCF(beta-TrCP) mutant results in an overextension phenotype.Together, our data provide evidence that Wnt-mediated axon guidance can be transduced through a beta-catenin-dependent pathway

Medium Chain Fatty Acids Are Selective Peroxisome Proliferator Activated Receptor (PPAR) γ Activators and Pan-PPAR Partial Agonists

Thiazolidinediones (TZDs) act through peroxisome proliferator activated receptor (PPAR) γ to increase insulin sensitivity in type 2 diabetes (T2DM), but deleterious effects of these ligands mean that selective modulators with improved clinical profiles are needed. We obtained a crystal structure of PPARγ ligand binding domain (LBD) and found that the ligand binding pocket (LBP) is occupied by bacterial medium chain fatty acids (MCFAs). We verified that MCFAs (C8–C10) bind the PPARγ LBD in vitro and showed that they are low-potency partial agonists that display assay-specific actions relative to TZDs; they act as very weak partial agonists in transfections with PPARγ LBD, stronger partial agonists with full length PPARγ and exhibit full blockade of PPARγ phosphorylation by cyclin-dependent kinase 5 (cdk5), linked to reversal of adipose tissue insulin resistance. MCFAs that bind PPARγ also antagonize TZD-dependent adipogenesis in vitro. X-ray structure B-factor analysis and molecular dynamics (MD) simulations suggest that MCFAs weakly stabilize C-terminal activation helix (H) 12 relative to TZDs and this effect is highly dependent on chain length. By contrast, MCFAs preferentially stabilize the H2-H3/β-sheet region and the helix (H) 11-H12 loop relative to TZDs and we propose that MCFA assay-specific actions are linked to their unique binding mode and suggest that it may be possible to identify selective PPARγ modulators with useful clinical profiles among natural products

Adapting agricultural water use to climate change in a post-Soviet context: challenges and opportunities in southeast Kazakhstan

The convergence of climate change and post-Soviet socio-economic and institutional transformations has been underexplored so far, as have the consequences of such convergence on crop agriculture in Central Asia. This paper provides a place-based analysis of constraints and opportunities for adaptation to climate change, with a specific focus on water use, in two districts in southeast Kazakhstan. Data were collected by 2 multi-stakeholder participatory workshops, 21 semi-structured in-depth interviews, and secondary statistical data. The present-day agricultural system is characterised by enduring Soviet-era management structures, but without state inputs that previously sustained agricultural productivity. Low margins of profitability on many privatised farms mean that attempts to implement integrated water management have produced water users associations unable to maintain and upgrade a deteriorating irrigation infrastructure. Although actors engage in tactical adaptation measures, necessary structural adaptation of the irrigation system remains difficult without significant public or private investments. Market-based water management models have been translated ambiguously to this region, which fails to encourage efficient water use and hinders adaptation to water stress. In addition, a mutual interdependence of informal networks and formal institutions characterises both state governance and everyday life in Kazakhstan. Such interdependence simultaneously facilitates operational and tactical adaptation, but hinders structural adaptation, as informal networks exist as a parallel system that achieves substantive outcomes while perpetuating the inertia and incapacity of the state bureaucracy. This article has relevance for critical understanding of integrated water management in practice and adaptation to climate change in post-Soviet institutional settings more broadly