Consistent interpretation of isotope and chemical oxygen exchange relaxation kinetics in SrFe0.85Mo0.15O3-δ ferrite.

This paper is devoted to the study of phase composition and kinetic and thermodynamic characteristics of Mo-doped strontium ferrite SrFe0.85Mo0.15O3-δ (SFM15) under oxygen-conducting membrane working conditions. Single-phase SFM15 with a cubic Pm3̄m structure was synthesized using a ceramic method. It was shown that the molybdenum introduction stabilizes the perovskite cubic structure over a wide range of oxygen pressures and temperatures, preventing the bulk phase transition at high temperatures. Oxygen exchange constants, diffusion coefficients and activation energy of oxygen exchange were obtained using oxygen relaxation and isotopic exchange techniques, and the obtained values are consistent with known literature data. It was shown that the surface reaction rates obtained using chemical and tracer relaxation methods are quantitatively comparable with each other, despite significantly different experimental conditions. This result not only confirms the reliability of the data obtained by independent methods, but also allows one to expand the area of physical conditions for studying the kinetics of oxygen transfer where another method has technical or methodological limitations.

The Role of Transcription Factor PPAR-γ in the Pathogenesis of Psoriasis, Skin Cells, and Immune Cells.

The peroxisome proliferator-activated receptor PPAR-γ is one of three PPAR nuclear receptors that act as ligand-activated transcription factors. In immune cells, the skin, and other organs, PPAR-γ regulates lipid, glucose, and amino acid metabolism. The receptor translates nutritional, pharmacological, and metabolic stimuli into the changes in gene expression. The activation of PPAR-γ promotes cell differentiation, reduces the proliferation rate, and modulates the immune response. In the skin, PPARs also contribute to the functioning of the skin barrier. Since we know that the route from identification to the registration of drugs is long and expensive, PPAR-γ agonists already approved for other diseases may also represent a high interest for psoriasis. In this review, we discuss the role of PPAR-γ in the activation, differentiation, and proliferation of skin and immune cells affected by psoriasis and in contributing to the pathogenesis of the disease. We also evaluate whether the agonists of PPAR-γ may become one of the therapeutic options to suppress the inflammatory response in lesional psoriatic skin and decrease the influence of comorbidities associated with psoriasis.

Role of the Transcription Factor FOSL1 in Organ Development and Tumorigenesis.

The transcription factor FOSL1 plays an important role in cell differentiation and tumorigenesis. Primarily, FOSL1 is crucial for the differentiation of several cell lineages, namely adipocytes, chondrocytes, and osteoblasts. In solid tumors, FOSL1 controls the progression of tumor cells through the epithelial-mesenchymal transformation. In this review, we summarize the available data on FOSL1 expression, stabilization, and degradation in the cell. We discuss how FOSL1 is integrated into the intracellular signaling mechanisms and provide a comprehensive analysis of FOSL1 influence on gene expression. We also analyze the pathological changes caused by altered Fosl1 expression in genetically modified mice. In addition, we dedicated a separate section of the review to the role of FOSL1 in human cancer. Primarily, we focus on the FOSL1 expression pattern in solid tumors, FOSL1 importance as a prognostic factor, and FOSL1 perspectives as a molecular target for anticancer therapy.

Analysis of PPARγ Signaling Activity in Psoriasis.

In our previous work, we built the model of PPARγ dependent pathways involved in the development of the psoriatic lesions. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and transcription factor which regulates the expression of many proinflammatory genes. We tested the hypothesis that low levels of PPARγ expression promote the development of psoriatic lesions triggering the IL17-related signaling cascade. Skin samples of normally looking and lesional skin donated by psoriasis patients and psoriatic CD3+ Tcells samples (n = 23) and samples of healthy CD3+ T cells donated by volunteers (n = 10) were analyzed by real-time PCR, ELISA and immunohistochemistry analysis. We found that the expression of PPARγ is downregulated in human psoriatic skin and laser treatment restores the expression. The expression of IL17, STAT3, FOXP3, and RORC in psoriatic skin before and after laser treatment were correlated with PPARγ expression according to the reconstructed model of PPARγ pathway in psoriasis.In conclusion, we report that PPARγ weakens the expression of genes that contribute in the development of psoriatic lesion. Our data show that transcriptional regulation of PPARγ expression by FOSL1 and by STAT3/FOSL1 feedback loop may be central in the psoriatic skin and T-cells.

Multi-scale problem in the model of RNA virus evolution.

A mathematical or computational model in evolutionary biology should necessary combine several comparatively fast processes, which actually drive natural selection and evolution, with a very slow process of evolution. As a result, several very different time scales are simultaneously present in the model; this makes its analytical study an extremely difficult task. However, the significant difference of the time scales implies the existence of a possibility of the model order reduction through a process of time separation. In this paper we conduct the procedure of model order reduction for a reasonably simple model of RNA virus evolution reducing the original system of three integro-partial derivative equations to a single equation. Computations confirm that there is a good fit between the results for the original and reduced models.

Genome-wide computational determination of the human metalloproteome.

Accurate prediction of protein function in humans is important for understanding biological processes at the molecular level in biomedicine and drug design. Over a third of proteins are commonly held to bind metal, and ∼10% of human proteins, to bind zinc. Therefore, an initial step in protein function prediction frequently involves predicting metal ion binding. In recent years, methods have been developed to predict a set of residues in 3D space forming the metal-ion binding site, often with a high degree of accuracy. Here, using extensions of these methods, we provide an extensive list of human proteins and their putative metal ion binding site residues, using translated gene sequences derived from the complete, resolved human genome. Under conditions of ∼90% selectivity, over 900 new human putative metal ion binding proteins are identified. A statistical analysis of resolved metal ion binding sites in the human metalloproteome is furnished and the importance of remote homology analysis is demonstrated. As an example, a novel metal-ion binding site involving a complex of a botulinum substrate with its inhibitor is presented. On the basis of the location of the predicted site and the interactions of the contacting residues at the complex interface, we postulate that metal ion binding in this region could influence complex formation and, consequently, the functioning of the protein. Thus, this work provides testable hypotheses about novel functions of known proteins.

HGF, HNRPD, and sFLT1 Interfere with the Induction of VEGF in Patients with Severe Psoriasis.

BACKGROUND: Restructuring of dermal microcapillaries is one of the hallmarks of plaque psoriasis. To control the proliferation of vascular endothelial cells, vascular endothelial growth factor (VEGF) promotes the remodeling of the existing blood vessels and angiogenesis. OBJECTIVE: This study aimed to explain the lowering protein and mRNA levels of VEGF in lesional skin of patients with severe psoriasis (the Psoriasis Area and Severity Index, PASI > 25). METHODS: Using the method of qPCR, we assessed the expression of VEGF mRNA in lesional and nonlesional psoriatic skin. Using ELISA, we also compared the levels of VEGF in skin homogenates of psoriasis patients and healthy volunteers. RESULTS: We found that the exacerbation of psoriasis induced VEGF on mRNA and protein levels 12 and 20 times, respectively. We also confirmed a strong correlation between VEGF and PASI score in patients with PASI < 25. In addition, we showed that several factors, namely HGF, HNRPD, and sFLT1 interfere with the biosynthesis of VEGF in skin lesions of patients with PASI > 25%. CONCLUSION: Thus, using VEGF as a biomarker to monitor the disease shall be done cautiously in patients with severe psoriasis.

Structure of ALD1, a plant-specific homologue of the universal diaminopimelate aminotransferase enzyme of lysine biosynthesis.

Diaminopimelate aminotransferase (DAP-AT) is an enzyme in the lysine-biosynthesis pathway. Conversely, ALD1, a close homologue of DAP-AT in plants, uses lysine as a substrate in vitro. Both proteins require pyridoxal-5'-phosphate (PLP) for their activity. The structure of ALD1 from the flowering plant Arabidopsis thaliana (AtALD1) was solved at a resolution of 2.3 Å. Comparison of AtALD1 with the previously solved structure of A. thaliana DAP-AT (AtDAP-AT) revealed similar interactions with PLP despite sequence differences within the PLP-binding site. However, sequence differences between the binding site of AtDAP-AT for malate, a purported mimic of substrate binding, and the corresponding site in AtALD1 led to different interactions. This suggests that either the substrate itself, or the substrate-binding mode, differs in the two proteins, supporting the known in vitro findings.

Ru Catalysts Supported on Bamboo-like N-Doped Carbon Nanotubes: Activity and Stability in Oxidizing and Reducing Environment.

The catalysts with platinum-group metals on nanostructured carbons have been a very active field of research, but the studies were mainly limited to Pt and Pd. Here, Ru catalysts based on nitrogen-doped carbon nanotubes (N-CNTs) have been prepared and thoroughly characterized; Ru loading was kept constant (3 wt.%), while the degree of N-doping was varied (from 0 to 4.8 at.%) to evaluate its influence on the state of supported metal. Using the N-CNTs afforded ultrafine Ru particles (<2 nm) and allowed a portion of Ru to be stabilized in an atomic state. The presence of Ru single atoms in Ru/N-CNTs expectedly increased catalytic activity and selectivity in the formic acid decomposition (FAD) but had no effect in catalytic wet air oxidation (CWAO) of phenol, thus arguing against a key role of single-atom catalysis in the latter case. A remarkable difference between these two reactions was also found in regard to catalyst stability. In the course of FAD, no changes in the support or supported species or reaction rate were observed even at a high temperature (150 °C). In CWAO, although 100% conversions were still achievable in repeated runs, the oxidizing environment caused partial destruction of N-CNTs and progressive deactivation of the Ru surface by carbonaceous deposits. These findings add important new knowledge about the properties and applicability of Ru@C nanosystems.

Laser Therapy Changes the Expression of Matrix Metalloproteinases in Bleomycin-Induced Skin Fibrosis.

Matrix metalloproteinases (MMPs) are often considered biomarkers of skin fibrosis. At the early stages of the pathological process, an elevation of their enzymatic activity causes significant changes in the composition of the extracellular matrix. MMPs secreted by immune cells facilitate their migration to the site of damage. Then, the immune cells eliminate the affected cells and biomolecules. Moreover, bidirectional changes in the activity of proteolytic enzymes, including MMPs, accompany wound healing. This study aimed to assess changes in the expression of Mmp2, Mmp3, and Mmp9 after treating mice with laser therapy using the experimental model of bleomycin-induced skin fibrosis. Using immunohistochemistry, we characterized the histological features of scarred skin. We also analyzed changes in the expression of MMPs using real-time polymerase chain reaction before and after laser irradiation. We showed that treatment of the mice with a CO2 laser partially normalized the histological features of scarred skin. We also noticed a decrease in the expression of Mmp2, Mmp3 (both p < 0.05), and Mmp9 (p = 0.065) during scar healing. The obtained results suggest that normalization of skin homeostasis requires control of MMP activity via induction of genes.

Dependence of Electrochemical Properties of MK-40 Heterogeneous Membrane on Number of Adsorbed Layers of Polymers.

The creation of monovalent selective ion exchange membranes benefits the desalination of surface waters by removing interfering monovalent ions while preserving polyvalent ionic nutrients. Studies of a promising method of layer-by-layer adsorption of polymers for the creation of monovalent selective coatings note a significant effect of the number of formed layers and of the nature of the external layer on the properties of the resulting membranes. This article reports the changes in properties of layer-by-layer coated heterogeneous membranes occurring at increasing numbers of layers that are attributed to the supposed intermixing of polymers between the layers, namely dependence of limiting current densities determined from i-V curve, enhanced electroconvection that was attributed to the appearing electrical heterogeneity of the surface, and the decreasing monovalent selectivity in electrodialysis of mixed NaCl + CaCl2 solution (from 1.33 to about 1) between the samples with five and six to eight layers of polymers.

Modeling the Conductivity and Diffusion Permeability of a Track-Etched Membrane Taking into Account a Loose Layer.

The microheterogeneous model makes it possible to describe the main transport properties of ion-exchange membranes using a single set of input parameters. This paper describes an adaptation of the microheterogeneous model for describing the electrical conductivity and diffusion permeability of a track-etched membrane (TEM). Usually, the transport parameters of TEMs are evaluated assuming that ion transfer occurs through the solution filling the membrane pores, which are cylindrical and oriented normally to the membrane surface. The version of the microheterogeneous model developed in this paper takes into account the presence of a loose layer, which forms as an intermediate layer between the pore solution and the membrane bulk material during track etching. It is assumed that this layer can be considered as a "gel phase" in the framework of the microheterogeneous model due to the fixed hydroxyl and carboxyl groups, which imparts ion exchange properties to the loose layer. The qualitative and quantitative agreement between the calculated and experimental concentration dependencies of the conductivity and diffusion permeability is discussed. The role of the model input parameters is described in relation to the structural features of the membrane. In particular, the inclination of the pores relative to the surface and their narrowing in the middle part of the membrane can be important for their properties.

Proteomic Studies of Psoriasis.

In this review paper, we discuss the contribution of proteomic studies to the discovery of disease-specific biomarkers to monitor the disease and evaluate available treatment options for psoriasis. Psoriasis is one of the most prevalent skin disorders driven by a Th17-specific immune response. Although potential patients have a genetic predisposition to psoriasis, the etiology of the disease remains unknown. During the last two decades, proteomics became deeply integrated with psoriatic research. The data obtained in proteomic studies facilitated the discovery of novel mechanisms and the verification of many experimental hypotheses of the disease pathogenesis. The detailed data analysis revealed multiple differentially expressed proteins and significant changes in proteome associated with the disease and drug efficacy. In this respect, there is a need for proteomic studies to characterize the role of the disease-specific biomarkers in the pathogenesis of psoriasis, develop clinical applications to choose the most efficient treatment options and monitor the therapeutic response.

First- and second-shell metal binding residues in human proteins are disproportionately associated with disease-related SNPs.

Protein structure serves as a key determinant for revealing the molecular basis of human disease. Metal ions are among the most frequently bound heterogroups in proteins affecting structure and function. We analyzed the relationship between single nucleotide polymorphisms (SNPs) associated with human disease and metal binding sites in proteins on a database scale, using structural models and predictive tools. A match was identified for 586 disease-associated SNPs (dSNPs) located at 135 predicted metal binding sites and associated with 126 diverse diseases. For 104 diseases, a metal is known to bind at the predicted site in the homologue; for 22, the analysis gives a first indication for metal involvement in the disease. As second-shell residues play an important part in metal ion binding, our analysis included protein space up to 4.5 Å from metal binding sites. The ratio of disease-associated versus nondisease-associated SNPs (dSNP/ndSNP) for first-shell residues is 7.4 and for second-shell residues, 3.1. In addition, over 13% of all dSNPs were found to be associated with first- and second-shell residues, although these residues occupy only about 3% of protein space. These results show a disproportionate association of dSNPs and metal binding sites over a wide variety of diseases.

Layer-by-Layer Coating of MK-40 Heterogeneous Membrane with Polyelectrolytes Creates Samples with Low Electrical Resistance and Weak Generation of H+ and OH- Ions.

Ion exchange membranes covered with layers of polyelectrolytes of alternating charges are characterized by very high monovalent selectivity. This allows the use of such membranes for electrodialytic fractionation of multicomponent solutions. However, the very existence of the boundary at which differently charged layers come in contact can hinder a membrane's effectiveness by limiting its ion permeability, raising levels of H+ and OH- ions (thus shifting the pH) and increasing the electrical resistance of the membrane, which leads to increased energy consumption. To test how these properties would be changed, we created cheap layer-by-layer-modified membranes based on the heterogeneous MK-40 membrane, on which we adsorbed layers of polyallylamine and sulfonated polystyrene. We created samples with 3, 4, and 5 layers of polyelectrolytes and characterized them. We showed that the application of layers did not decrease the efficiency of the membrane, since the electrical resistance of the modified samples, which increased after application of the first oppositely charged layer, declined with the application of the following layers and became comparable to that of the substrate, while their limiting current density was higher and the shift of pH of treated solution was low in magnitude and comparable with that of the substrate membrane.

Novel Mutation in the Acetohydroxyacid Synthase (AHAS), Gene Confers Imidazolinone Resistance in Chickpea Cicer arietinum L. Plants.

Chickpea (Cicer arietinum L.) is an important crop in crop-rotation management in Israel. Imidazolinone herbicides have a wide spectrum of weed control, but chickpea plants are sensitive to acetohydroxyacid synthase (AHAS; also known as acetolactate synthase [ALS]) inhibitors. Using the chemical mutagen ethyl methanesulfonate (EMS), we developed a chickpea line (M2033) that is resistant to imidazolinone herbicides. A point mutation was detected in one of the two genes encoding the AHAS catalytic subunit of M2033. The transition of threonine to isoleucine at position 192 (203 according to Arabidopsis) conferred resistance of M2033 to imidazolinones, but not to other groups of AHAS inhibitors. The role of this substitution in the resistance of line M2033 was proven by genetic transformation of tobacco plants. This resistance showed a single-gene semidominant inheritance pattern. Conclusion: A novel mutation, T192I (T203I according to Arabidopsis), providing resistance to IMI herbicides but not to other groups of AHAS inhibitors, is described in the AHAS1 protein of EMS-mutagenized chickpea line M2033.

Differential Expression of Estrogen-Responsive Genes in Women with Psoriasis.

In women, the flow of psoriasis is influenced by each phase of a woman's life cycle. According to previous findings, significant changes in the levels of sex hormones affect the severity of the disease. Aim: The aim of this study was to identify the estrogen-responsive genes that could be responsible for the exacerbation of psoriasis in menopausal women. Methods: Skin samples of lesional skin donated by psoriasis patients (n = 5) were compared with skin samples of healthy volunteers (n = 5) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The set of differentially expressed proteins was subjected to protein ontology analysis to identify differentially expressed estrogen-responsive proteins. The expression of discovered proteins was validated by qPCR and ELISA on four groups of female participants. The first group included ten psoriasis patients without menopause; the second included eleven postmenopausal patients; the third included five healthy volunteers without menopause; and the fourth included six postmenopausal volunteers. Moreover, the participants' blood samples were used to assess the levels of estradiol, progesterone, and testosterone. Results: We found that the levels of estradiol and progesterone were significantly lower and the levels of testosterone were significantly higher in the blood of patients compared to the control. The protein ontology analysis of LC-MS/MS data identified six proteins, namely HMOX1, KRT19, LDHA, HSPD1, MAPK1, and CA2, differentially expressed in the lesional skin of female patients compared to male patients. ELISA and qPCR experiments confirmed differential expression of the named proteins and their mRNA. The genes encoding the named proteins were differentially expressed in patients compared to volunteers. However, KRT19 and LDHA were not differentially expressed when we compared patients with and without menopause. All genes, except MAPK1, were differentially expressed in patients with menopause compared to the volunteers with menopause. HMOX1, KRT19, HSPD1, and LDHA were differentially expressed in patients without menopause compared to the volunteers without menopause. However, no significant changes were found when we compared healthy volunteers with and without menopause. Conclusion: Our experiments discovered a differential expression of six estrogen-controlled genes in the skin of female patients. Identification of these genes and assessment of the changes in their expression provide insight into the biological effects of estrogen in lesional skin. The results of proteomic analysis are available via ProteomeXchange with identifier PXD021673.

Characterization of MK-40 Membrane Modified by Layers of Cation Exchange and Anion Exchange Polyelectrolytes.

Coating of ion exchange membranes used in electrodialysis with layers of polyelectrolytes is a proven approach that allows for the increasing of the limiting current, the suppressing of sedimentation, the controlling of the intensity of generation of H+ and OH- ions, and also the improving of monovalent selectivity. However, in the case when two materials with the opposite sign of the charge of fixed groups come in contact, a bipolar boundary is created that can cause undesirable changes in the membrane properties. In this work, we used a MK-40 heterogeneous membrane on the surface of which a layer of polyethyleneimine was applied by adsorption from a solution as a model of heterogeneous membranes modified with oppositely charged polyelectrolyte. It was found that, on one hand, the properties of modified membrane were beneficial for electrodialysis, its limiting current did not decrease and the membrane even acquired a barrier to non-selective electrolyte transport. At the same time, the generation of H+ and OH- ions of low intensity arose, even in underlimiting current modes. It was also shown that despite the presence of a layer of polyethyleneimine, the surface charge of the modified membrane remained negative, which we associate with low protonation of polyethyleneimine at neutral pH.

The Model of PPARγ-Downregulated Signaling in Psoriasis.

Interactions of genes in intersecting signaling pathways, as well as environmental influences, are required for the development of psoriasis. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and transcription factor which inhibits the expression of many proinflammatory genes. We tested the hypothesis that low levels of PPARγ expression promote the development of psoriatic lesions. We combined experimental results and network functional analysis to reconstruct the model of PPARγ-downregulated signaling in psoriasis. We hypothesize that the expression of IL17, STAT3, FOXP3, and RORC and FOSL1 genes in psoriatic skin is correlated with the level of PPARγ expression, and they belong to the same signaling pathway that regulates the development of psoriasis lesion.

Superhydrophobic copper in biological liquids: Antibacterial activity and microbiologically induced or inhibited corrosion.

The bactericidal activity of copper and copper alloys is well appreciated and was already exploited in medical practice in 19th century. However, despite of being an essential nutrient required by organisms to perform life functions, excess copper is extremely toxic and detrimental to health. Recent studies have shown that superhydrophobic surfaces have a significant antibacterial potential for reduction of nosocomial infections. At the same time, the prolonged contact with biological liquids may cause a degradation of the superhydrophobic copper surface and corrosion with increasing egress of toxic copper ions. These aspects are poorly studied so far. In this paper, we analyze the evolution of the properties of both the superhydrophobic copper surface and the suspension of Escherichia coli bacteria during their prolonged contact and study the impact of such contact on the bactericidal activity of the surface. It is shown that by controlling the corrosion resistance and the wettability of the superhydrophobic copper substrate, it becomes possible to sustain the bactericidal action of copper substrates for a long time, simultaneously avoiding the excessive corrosive degradation and release of copper ions in the environment.