Favorable Regions Research Articles

Quercetin: A promising drug candidate against the potential SARS-CoV-2-Spike mutants with high viral infectivity

The emergence of SARS-CoV-2-Spike mutants not only enhances viral infectivity but also lead to treatment failure. Gaining a comprehensive understanding of the molecular binding mode between the mutant SARS-CoV-2-Spike and human ACE2 receptor is crucial for therapeutic development against this virus. Building upon our previous predictions and verifications regarding heightened viral infectivity of six potential SARS-CoV-2-Spike mutants, this study aims to further investigate the potential disruption of the interaction between these mutants and ACE2 by quercetin, a Chinese herbal compound. Molecular docking and dynamics simulations results reveal that the binding sites of quercetin particularly enriched around a specific “cavity” at the interface of Spike/ACE2 complex, indicating a favorable region for quercetin to interfere with Spike/ACE2 interaction. Virus infection assay confirms that quercetin not only attenuates wild-type virus infectivity but also suppresses the infectivity of all six tested SARS-CoV-2-Spike mutants. Therefore, quercetin represents a promising therapeutic candidate against both wild-type and potential future variants of SARS-CoV-2 exhibiting high viral infectivity.

In silico Structure Prediction, Molecular Docking, and Dynamic Simulation of Plasmodium falciparum AP2-I Transcription Factor.

Plasmodium falciparum Apicomplexan Apetala 2 Invasion (PfAP2-I) transcription factor (TF) is a protein that regulates the expression of a subset of gene families involved in P. falciparum red blood cell (RBC) invasion. Inhibiting PfAP2-I TF with small molecules represents a potential new antimalarial therapeutic target to combat drug resistance, which this study aims to achieve. The 3D model structure of PfAP2-I was predicted ab initio using ROBETTA prediction tool and was validated using Save server 6.0 and MolProbity. Computed Atlas of Surface Topography of proteins (CASTp) 3.0 was used to predict the active sites of the PfAP2-I modeled structure. Pharmacophore modeling of the control ligand and PfAP2-I modeled structure was carried out using the Pharmit server to obtain several compounds used for molecular docking analysis. Molecular docking and postdocking studies were conducted using AutoDock vina and Discovery studio. The designed ligands' toxicity predictions and in silico drug-likeness were performed using the SwissADME predictor and OSIRIS Property Explorer. The modeled protein structure from the ROBETTA showed a validation result of 96.827 for ERRAT, 90.2% of the amino acid residues in the most favored region for the Ramachandran plot, and MolProbity score of 1.30 in the 98th percentile. Five (5) best hit compounds from molecular docking analysis were selected based on their binding affinity (between -8.9 and -11.7 Kcal/mol) to the active site of PfAP2-I and were considered for postdocking studies. For the absorption, distribution, metabolism, elimination, and toxicity (ADMET) properties, compound MCULE-7146940834 had the highest drug score (0.63) and drug-likeness (6.76). MCULE-7146940834 maintained a stable conformation within the flexible protein's active site during simulation. The good, estimated binding energies, drug-likeness, drug score, and molecular dynamics simulation interaction observed for MCULE-7146940834 against PfAP2-I show that MCULE-7146940834 can be considered a lead candidate for PfAP2-I inhibition. Experimental validations should be carried out to ascertain the efficacy of these predicted best hit compounds.

Methane gas hydrates of the Black Sea – environmental problem or energy source?

Purpose. The purpose of this paper is to substantiate the technological solution of equilibrium conditions in the system “methane – water phase – hydrate – R-2M”; to reveal existing ecological problems of methane gas hydrate extraction from the Black Sea bottom; to determine whether gas hydrate deposits of Black Sea methane are an ecological problem or should be considered as an energy source, to explain the necessity of introduction of the effect of forced self-preservation of methane gas hydrates into development of gas hydrates from the sea bottom.
 Results. This article analyses current research on gas hydrates specifically in the Black Sea. It shows that the necessary conditions exist for the accumulation of gas hydrates in certain areas of the deep Black Sea (one of the most favourable regions among modern sea basins). This article discusses some ideas for the development of experimental studies of the metastable state of methane gas hydrates at negative temperatures: stability and mechanisms of decomposition. Despite the great variety of technological solutions and schemes of gas hydrates application proposed by the leading researchers in the world, they have been tested practically on a small number of laboratory and model installations, mainly for water desalination and concentration of water solutions, separation of two-component gas mixtures. In fact, there is no data to calculate the processes of formation and melting of ice-gas hydrate methane. The effect of self-preservation of methane gas hydrates deserves special attention.
 Scientific novelty. An attempt was made to substantiate the issue of whether gas hydrate deposits of methane in the Black Sea are an environmental problem or should they be considered as an additional source of energy and even as a “fuel of the future”. The authors for the first time introduced the concept of “forced preservation (activation) effect of methane gas hydrates”, which makes it possible to stabilize methane hydrate decomposition when the system is transferred from the area of hydrate stability to the area of thermodynamic parameters, thus significantly reducing the environmental problems of the Black Sea.
 Practical value. This article offers a technological solution for stabilization of equilibrium conditions by hydrophobic material “Ramsinks-2M” in the system “methane-water phase-hydrate-R-2M” to regulate the self-preservation effect of methane gas hydrates

Carbon Isotope Fractionation Characteristics of Normally Pressured Shale Gas from the Southeastern Margin of the Sichuan Basin; Insights into Shale Gas Storage Mechanisms

Since the development of shale gas in the Wufeng-Longmaxi Formation in the Sichuan Basin, China's shale gas production and reserves have increased rapidly. The southeastern margin of the Sichuan Basin is located in a normally pressured transition zone, where single well gas production varies greatly under complex geological structures. In order to reveal the shale gas enrichment mechanism and favorable shale gas regions, shale gas samples from production wells were collected from different structures, with the formation pressure coefficient ranging between 0.98 and 1.35. The gas components and carbon isotope characteristics of normally pressured shale gas were investigated. The carbon isotope characteristics of the Wufeng-Longmaxi shale gas from the basin scale was mainly controlled using thermal maturity; as the thermal maturity increased, heavier carbon isotopes were found, in addition to drier shale gas. For normally pressured shale gas, the composition of δ13C1 and δ13C2 becomes heavier, and the dryness coefficient decreases with the decreasing pressure coefficient; this is not consistent with the results from thermal evolution. By comparing possible influencing factors, it is evident that the change in geological structure destroys the original shale gas reservoir, which leads to the escape of some gases, and it may be the main factor that contributes to the gas geochemical characteristics of the normally pressured shale gas. Compared with the geological parameters of the shale samples, such as mineral composition, organic abundance, organic pore distribution, and gas content, the carbon isotope characteristics of normally pressured shale gas show a higher efficiency, thus indicating favorable sweet spot evaluations for shale gas in the studied areas.

Fractal Structure Characteristics and Prospecting Direction of Dispersed Metals in the Eastern Guizhou Pb–Zn Metallogenic Belt, SW China

The eastern Guizhou Pb–Zn metallogenic belt (EGMB) is an important source of Pb–Zn resources and other critical minerals (including dispersed metals, such as Ge, Cd and Ga) in China. In order to ensure the continuous resource supply of Pb–Zn and associated dispersed metals, it is urgent to explore the direction of further prospecting for them. Fractal theory can realize the fractal structure characterization of fault structures and the spatial distribution of mineral deposits, which is helpful for mineral exploration. However, the fault fractal research and prospecting application are still seldom covered in the EGMB. We used fractal theory to determine fine-scale fractal structure characteristics of fault structures and ore deposits in the EGMB, and Fry analysis to delineate favorable metallogenic areas. The results show that within a scale range of 3.670–58.716 km, the integrated faults capacity dimension (CPD) is 1.5095, the information dimension (IND) is 1.5391, and the correlation dimension (CRD) is 1.5436, indicating fault structures with high maturity, which are conducive to the migration and accumulation of ore-forming fluids. The multi-fractal spectrum width and height are 0.3203 and 1.5355, respectively, implying a significant metallogenic potential. The spatial distribution fractal dimensions (SDD) of Pb–Zn specifically and metal deposits in general are 1.0193 and 1.0709, respectively; the quantity distribution fractal dimensions (QDD) are 1.4225 and 1.4716, respectively, and the density distribution fractal dimensions (DDD) are 1.422 and 1.472, respectively, indicating strong clustering. Hence, the favorable metallogenic regions can be divided into four grades, among which grade I region is continuously distributed in space and has the greatest prospecting potential.

Hidden Hearts of Neutrino Active Galaxies

Recent multimessenger studies have provided evidence for high-energy neutrino sources that are opaque to GeV–TeV gamma rays. We present model-independent studies on the connection between neutrinos and gamma rays in the active galaxy NGC 1068, and find that the neutrinos most likely come from regions within ∼30–100 Schwarzschild radii. This is especially the case if neutrinos are produced via the photomeson production process, although the constraints could be alleviated if hadronuclear interactions are dominant. We consider the most favorable neutrino production regions, and discuss coronae, jets, winds, and their interactions with dense material. The results strengthen the importance of understanding dissipation mechanisms near the coronal region and the outflow base. There could be a connection between active galactic nuclei with near-Eddington accretion and tidal disruptions events, in that neutrinos are produced in the obscured vicinity of supermassive black holes.

Mass transfer rate and osmotic treatment efficiency of peaches

Abstract The highest-quality peaches [Prunus persica (L.) Batsch] are cultivated in areas with sunny summers, therefore the territory of the Autonomous Province of Vojvodina is a favourable region for their production. Peaches are usually consumed fresh, canned, or dried and represent a great source of the essential nutrients. Osmotic dehydration is a well-known preservation method that relies on mild temperatures and requires low energy. Research conducted at the Faculty of Technology Novi Sad has introduced sugar beet molasses as an efficient osmotic solution for drying various food samples. In this research, peach samples were osmotically treated in sugar beet molasses, and the goal was to investigate the impact of different solution concentrations, temperatures, and immersion time on the mass transfer rate and the efficiency of treatment. The results have shown that the mass transfer rate during the osmotic treatment of peach samples in sugar beet molasses was the most intensive at the beginning of the process, at the highest solution concertation, and at the highest temperature. In accordance with the results, diffusion occurred most rapidly during the first three hours of the process; therefore, processing time can be reduced.

Genome-wide identification, comprehensive characterization of transcription factors, cis-regulatory elements, protein homology, and protein interaction network of DREB gene family in Solanum lycopersicum.

Tomato is a drought-sensitive crop which has high susceptibility to adverse climatic changes. Dehydration-responsive element-binding (DREB) are significant plant transcription factors that have a vital role in regulating plant abiotic stress tolerance by networking with DRE/CRT cis-regulatory elements in response to stresses. In this study, bioinformatics analysis was performed to conduct the genome-wide identification and characterization of DREB genes and promoter elements in Solanum lycopersicum. In genome-wide coverage, 58 SlDREB genes were discovered on 12 chromosomes that justified the criteria of the presence of AP2 domain as conserved motifs. Intron-exon organization and motif analysis showed consistency with phylogenetic analysis and confirmed the absence of the A3 class, thus dividing the SlDREB genes into five categories. Gene expansion was observed through tandem duplication and segmental duplication gene events in SlDREB genes. Ka/Ks values were calculated in ortholog pairs that indicated divergence time and occurrence of purification selection during the evolutionary period. Synteny analysis demonstrated that 32 out of 58 and 47 out of 58 SlDREB genes were orthologs to Arabidopsis and Solanum tuberosum, respectively. Subcellular localization predicted that SlDREB genes were present in the nucleus and performed primary functions in DNA binding to regulate the transcriptional processes according to gene ontology. Cis-acting regulatory element analysis revealed the presence of 103 motifs in 2.5-kbp upstream promoter sequences of 58 SlDREB genes. Five representative SlDREB proteins were selected from the resultant DREB subgroups for 3D protein modeling through the Phyre2 server. All models confirmed about 90% residues in the favorable region through Ramachandran plot analysis. Moreover, active catalytic sites and occurrence in disorder regions indicated the structural and functional flexibility of SlDREB proteins. Protein association networks through STRING software suggested the potential interactors that belong to different gene families and are involved in regulating similar functional and biological processes. Transcriptome data analysis has revealed that the SlDREB gene family is engaged in defense response against drought and heat stress conditions in tomato. Overall, this comprehensive research reveals the identification and characterization of SlDREB genes that provide potential knowledge for improving abiotic stress tolerance in tomato.

Evaluation of the consistence between the results of immunoinformatics predictions and real-world animal experiments of a new tuberculosis vaccine MP3RT.

Our previous study developed a novel peptide-based vaccine, MP3RT, to fight against tuberculosis (TB) infection in a mouse model. However, the consistency between the immunoinformatics predictions and the results of real-world animal experiments on the MP3RT vaccine remains unclear. In this study, we predicted the antigenicity, immunogenicity, physicochemical parameters, secondary structure, and tertiary structure of MP3RT using bioinformatics technologies. The immune response properties of the MP3RT vaccine were then predicted using the C-ImmSim server. Finally, humanized mice were used to verify the characteristics of the humoral and cellular immune responses induced by the MP3RT vaccine. MP3RT is a non-toxic and non-allergenic vaccine with an antigenicity index of 0.88 and an immunogenicity index of 0.61, respectively. Our results showed that the MP3RT vaccine contained 53.36% α-helix in the secondary structure, and the favored region accounted for 98.22% in the optimized tertiary structure. The binding affinities of the MP3RT vaccine to the human leukocyte antigen (HLA)-DRB1*01:01 allele, toll-like receptor-2 (TLR-2), and TLR-4 receptors were -1234.1 kcal/mol, -1066.4 kcal/mol, and -1250.4 kcal/mol, respectively. The results of the C-ImmSim server showed that the MP3RT vaccine could stimulate T and B cells to produce immune responses, such as high levels of IgM and IgG antibodies, IFN-γ, TNF-α, and IL-2 cytokines. Results from real-world animal experiments showed that the MP3RT vaccine could stimulate the humanized mice to produce high levels of IgG and IgG2a antibodies and IFN-γ+ T lymphocytes. Furthermore, the levels of IFN-γ, IL-2, and IL-6 cytokines in mice immunized with the MP3RT vaccine were significantly higher than those in the control group. MP3RT is a highly antigenic and immunogenic potential vaccine that can effectively induce Th1-type immune responses in silico analysis and animal experiments. This study lays the foundation for evaluating the value of computational tools and immunoinformatic techniques in reverse vaccinology research.

Predicting the ignition sequences in a separated stratified swirling spray flame with stochastic flame particle tracking

Stochastic flame particle tracking in conjunction with non-reacting combustor simulations can offer insights into the ignition processes and facilitate the combustor optimization. In this study, this approach is employed to simulate the ignition sequences in a separated dual-swirl spray flame, in which the newly proposed pairwise mixing-reaction model is used to account for the mass and energy transfer between the flame particle and the surrounding shell layer. Based on the flame particle temperature, the particle state can be classified in to burnt, hot gas, and extinguished. The additional state of hot gas is introduced to allow the flame particles with high temperature to survive from nonflammable region and then potentially to ignite the nearby favourable regions. The simulations of the separated stratified swirl spray flame reveal two different ignition pathways for flame stabilization. The first showed that some flame particles from the spark would directly enter the main recirculation zone resulting from the velocity randomness and then ignite both sides of the combustor simultaneously. The second showed that flame particles from the spark would ignite the traversed regions following the swirl motion inside the combustor. The predicted ignition sequences were compared with the evolution of flame morphology recorded by high-speed imaging from experiments, showing qualitative agreement.

Tuberculosis in Adults and Children in the Northwestern Federal District: Changes in Epidemiological Rates and Criteria for Their Assessment

The epidemic situation is monitored by numerous rates that may not reflect it objectively which will subsequently lead to higher incidence rates and severe forms of tuberculosis in both adults and children in the regions with the most unfavorable situation.The objective: to evaluate epidemiological rates for tuberculosis in the Northwestern Federal District to identify the most significant, and assess the epidemic situation in the region using these most significant rates.Subjects and Methods. We analyzed the main epidemiological rates of pediatric tuberculosis according to federal statistics (Forms 8 and 33) in 11 districts of the Northwestern District in 2019-2021. Annual figures were obtained from open demographic data of the state statistics (https://www.fedstat.ru). Statistical analysis was pe`rformed using the free software R (v.3.5.1) and the commercial Statistical Package for the Social Sciences (SPSS Statistics for Windows, Version 24.0, IBM Corp., 2016). Hierarchical cluster analysis and k-means clustering were used with the selection of the lowest and highest values of rates. A formula is proposed for calculating the coefficient of full coverage with preventive screening (COP) for tuberculosis of the population which allows adjusting the analyzed epidemic rates taking into account the maximum coverage of the population with preventive screening and determining the accuracy of previous analysis.Results. According to the data obtained, in 2017 and 2018, Vologda Oblast and Nenets Autonomous Okrug were epidemically favorable regions, while in 2020 and 2021 Kaliningrad, Leningrad and Novgorod Oblasts were regarded as favorable regions that were steadily improving their performance. Regions with unfavorable tuberculosis situation include Pskov Oblast, St. Petersburg and the Komi Republic. At the same time, the first two regions occupy this position stably from 2017 to 2021. The use of the coefficient of low coverage with screening for tuberculosis made it possible to determine that Murmansk Oblast, St. Petersburg, Leningrad and Pskov Oblasts in 2020 and 2021 are prognostically unfavorable regions despite a decline in official tuberculosis rates. The data obtained correlate with a high percentage of positive tests with the tuberculosis recombinant tuberculosis allergen (TRA) in children in the regions mentioned above.Conclusions. The analysis of the data clearly demonstrates the possibility of determining the epidemically most favorable or unfavorable regions using four rates: coverage with preventive screening, incidence in the adult population, incidence in children aged 0 to 17 years, and tuberculosis mortality. Cluster analysis using these rates, calculation of rates using the developed coefficient of low coverage with screening for tuberculosis, and analysis of positive results of TRA test in children allows identifying the most epidemically unfavorable regions, despite the decrease in some rates that can be regarded as favorable.

Structural and thermostability insights into cellobiohydrolase of a thermophilic mould Myceliophthora thermophila: in-silico studies

Cellobiohydrolase (CBH) is one of the cellulases with a wide range of industrial applications; it plays a pivotal role in cellulose hydrolysis and thus in biofuel production. The structural and thermostability analysis of a CBHII of the thermophilic mold Myceliophthora thermophila (MtCel6A) had been carried out using various in-silico approaches. The validation of 3 D model by the Ramachandran plot indicated 88.5% amino acid residues in the favoured regions. Docking analysis suggested MtCel6A to display a high affinity towards cellotetraose as compared to other substrates. The enzyme exhibited a high tolerance to the end product, cellobiose. The thermostability evaluation by molecular dynamic simulations and principal component analysis confirmed its tolerance to elevated temperatures. The identified thermolabile regions could be targeted for site-directed mutagenesis in order to ameliorate thermostability further. Our experimental data published earlier confirmed the present findings of in-silico studies. The structural and functional characteristics of MtCel6A highlighted its critical features that make it a useful biocatalyst in several industrial processes. Communicated by Ramaswamy H. Sarma

Discovering hidden geothermal signatures using non-negative matrix factorization with customized k-means clustering

Discovery of hidden geothermal resources is challenging. It requires the mining of large datasets with diverse data attributes representing subsurface hydrogeological and geothermal conditions. The commonly used play fairway analysis approach typically incorporates subject-matter expertise to analyze regional data to estimate geothermal characteristics and favorability. We demonstrate an alternative approach based on machine learning (ML) to process a geothermal dataset from southwest New Mexico (SWNM). The study region includes low- and medium-temperature hydrothermal systems. Several of these systems are not well characterized because of insufficient existing data and limited past explorative work. This study discovers hidden patterns and relations in the SWNM geothermal dataset to improve our understanding of the regional hydrothermal conditions and energy-production favorability. This understanding is obtained by applying an unsupervised ML algorithm based on non-negative matrix factorization coupled with customized k-means clustering (NMFk). NMFk can automatically identify (1) hidden signatures characterizing analyzed datasets, (2) the optimal number of these signatures, (3) the dominant data attributes associated with each signature, and (4) the spatial distribution of the extracted signatures. Here, NMFk is applied to analyze 18 geological, geophysical, hydrogeological, and geothermal attributes at 44 locations in SWNM. Using NMFk, we find data patterns and identify the spatial associations of hydrothermal signatures within two physiographic provinces (Colorado Plateau and Basin and Range) and two sub-regions of these provinces (the Mogollon-Datil volcanic field and the Rio Grande rift) in SWNM. The ML algorithm extracted five hydrothermal signatures in the SWNM datasets that differentiate between low (<90°C) and medium (90-150°C)-temperature hydrothermal systems. The algorithm also suggests that the Rio Grande rift and northern Mogollon-Datil volcanic field are the most favorable regions for future geothermal resource discovery. NMFk also identified critical attributes to identify medium-temperature hydrothermal systems in the study area. The resulting NMFk model can be applied to predict geothermal conditions and their uncertainties at new SWNM locations based on limited data from unexplored regions. The code to execute the performed analyses as well as the corresponding data can be found at https://github.com/SmartTensors/GeoThermalCloud.jl.

Constraints on the dark photon from parity violation and the W mass

We present an analysis of the experimental data for parity-violating electron scattering (PVES) and atomic parity-violation, including the effects of a dark photon. We derive the favored region of dark photon parameter space, which provides a good description of the experimental data from the Qweak Collaboration and the Jefferson Lab PVDIS Collaboration and simultaneously relieves the tension between the neutron skin thickness determined in the PREX-II experiment and nuclear-model predictions. In addition, we extract the parameter region required to explain the latest W-boson mass anomaly. Our results indicate that a heavy dark photon with mass above the Z boson mass is favored, while other sources of new physics beyond the Standard Model in addition to the dark photon would also be expected.

Sustainable development of manganese sulfoselenide nanoparticles anchored graphene oxide nanocomposite for high-performance supercapacitor and lithium-ion battery applications

Transition metal chalcogenides have been described as promising electrode materials for supercapacitors due to their low electronegativity, suitable electrical conductivity, comparatively higher specific capacitance, and favorable electrochemical redox regions. However, the poor electrical conductivity and substantial volume fluctuations provide a significant obstacle to industrial use. A new method to develop metal incorporated GO at the time of GO synthesis and subsequent conversion to metal sulfoselenides is proposed and demonstrated here. This novel process incorporates the advantages of both GO and the metal sulfoselenides for electrochemical energy storage applications. The average size of the nanoclusters was 52 nm as identified by Transmission electron microscopy. As pseudocapacitive electrode GO-MnSSe delivered a specific capacitance of 603 F/g at 0.1 A/g in 1 M KCl of aqueous electrolyte, because of their distinct and stable form. The fabricated 2-electrode device showed a specific capacitance of 98.5 mF/cm2 at 80 µA/cm2, showing good retention of 67 % at the end of the 9000 cycles. As Li-ion battery half-cells, at specific currents of 50, 100, 250, and 500 mA/g, GO-MnS delivered a capacity of 587, 378, 273, and 211 mA h/g respectively, reflecting a retention rate of 64 %, while the specific current was increased 10 times. The initial capacity of GO-MnS and GO-MnSSe at 100 mA/g was 494 and 495 mAh/g respectively, and for GO-MnS and GO-MnSSe at 250 mA/g the delivered capacity values were 376 and 363 mA h/g respectively. Coulombic efficiency (CE) for GO, GO-SW (single wash), GO-MnS, and GO-MnSSe were 99.52 %, 99.6 %, 98.7 %, and 99 % respectively at the end of the 100 cycles. Moreover, GO-MnS were cycled at a higher rate of 500 mA/g for 500 cycles which showed a decay initially nevertheless it stabilized after few cycles and showed a retention of 88 % at the end of 500 cycles from 20th cycle. The ex-situ morphological analysis of GO-MnS were conducted as well as the kinetic of the electrode were studied by before and after cycling EIS measurement. As part of this, as an anode for lithium-ion batteries, high Li-ion storage capacity and cyclic stability were observed.

Red emitting fluorogenic dye as an efficient turn-on probe for milk allergen

Development of simple, fast and non-destructive technique such as fluorescence based method for the quantification of milk allergens in various dairy products is a highly rewarding task. In this contribution, a red emitting fluorogenic dye, quinaldine red (QR) is reported for the detection and quantification of a milk allergen, beta lactoglobulin (β-LG) in milk and whey matrices, utilizing its high selectivity and sensitivity towards β-LG. Detail spectroscopic investigation reveals that binding of QR to the hydrophobic calyx site of β-LG protein substantially reduces the torsional agility and propensity of TICT state formation of QR, rendering the dye highly fluorescent in nature. This enables estimation of β-LG with LOD 52.1(±0.9) nM in buffer solution and 0.21(±0.01) μM in 5 % bovine milk matrix respectively. Additionally, high selectivity and sensitivity, excellent repeatability, quick response, and emission in the biologically favorable red spectral region make QR based fluorometric quantification of β-LG a highly attractive choice. Finally, the estimated β-LG concentrations in milk and whey matrices from fluorometric titration and densitometry methods are found to match excellently with each other, suggesting potential of QR as an efficient turn-on fluorescent probe for the quantification of β-LG (milk allergen) in various dairy products.

Studying the Alkaloids Content in Delphinium oreophilum Huth

Research relevance: plant alkaloids are important in pharmacology based on their high physiological activity, as well as wide range of practical valuable medicinal properties. Most of plants necessary for conservation, cultivation and rational use of each type of plant resources in traditional and medical practice remains an urgent task. Kyrgyzstan is a favorable region for growth of medicinal herbs that is why flora research and study is of great importance. Research objectives: search of the biologically active content of methyllicaconitine alkaloids in roots and aerial parts of the Delphinium oreophilum plant growing in the territory of the Kyrgyz Republic. Research methods: diterpenoid alkaloids methyl lycaconitine, anthranoillicoctonine, lycoctonine, eldelin, eldelidine were obtained by separating the sum of alkaloids. Resulting compounds were analyzed by IR, NMR, Mass spectroscopy. A mixed melt test of the isolated perchlorate with a true sample of methyl lycaconitine perchlorate confirmed compounds identity. Research results: the sum of alkaloids obtained from the roots and aerial parts of Delphinium oreophilum plants collected in the southern and northern slopes of the Kichi Alai ridge. Conclusions: the content of total alkaloids in the roots and aerial parts of the plant growing in the southern slopes was 1.8% and 1% of the weight of the dry plant. The samples collected in the northern slopes contained 0.8% and 0.7% of the total alkaloids, respectively.

Insights into the Binding Interaction of Catechol 1,2-Dioxygenase with Catechol in Achromobacter xylosoxidans DN002.

Microbial remediation has become one of the promising ways to eliminate polycyclic aromatic hydrocarbons (PAHs) pollution due to its efficient enzyme metabolism system. Catechol 1,2-dioxygenase (C12O) is a crucial rate-limiting enzyme in the degradation pathway of PAHs in Achromobacter xylosoxidans DN002 that opens the benzene ring through the ortho-cleavage pathway. However, little attention has been given to explore the interaction mechanism of relevant enzyme-substrate. This study aims to investigate the binding interaction between C12O of strain DN002 and catechol by means of a molecular biological approach combined with homology modeling, molecular docking, and multiple spectroscopies. The removal rate of catechol in the mutant strain of cat A deletion was only 12.03%, compared to the wild-type strain (54.21%). A Ramachandran plot of active site regions of the primary amino acid sequences in the native enzyme showed that 93.5% sequences were in the most favored regions on account of the results of homology modeling, while an additional 6.2% amino acid sequences were found in conditionally allowed regions, and 0.4% in generously allowed regions. The binding pocket of C12O with catechol was analyzed to obtain that the catalytic trimeric group of Tyr164-His224-His226 was proven to be great vital for the ring-opening reaction of catechol by molecular docking. In the native enzyme, binding complexes were spontaneously formed by hydrophobic interactions. Binding constants and thermodynamic potentials from fluorescence spectra indicated that catechol effectively quenched the intrinsic fluorescence of C12O in the C12O/catechol complex via conventional static and dynamic quenching mechanisms of C12O. The results of ultraviolet and visible (UV) spectra, synchronous fluorescence, and circular dichroism (CD) spectra revealed conspicuous changes in the local conformation, and site-directed mutagenesis confirmed the role of predicted key residues during catalysis, wherein His226 had a significant effect on catechol utilization by C12O. This is the first report to reveal interactions of C12O with substrate from the molecular docking results, providing the mechanistic understanding of representative dioxygenases involved in aromatic compound degradation, and a solid foundation for further site modifications as well as strategies for the directed evolution of this enzyme.

Spectroscopic studies of 7,8-diacetoxy-4-methylcoumarin and 7,8-dipentynoyl-4-methylcoumarin binding with calreticulin.

Calreticulin (CRT) is a protein found mainly in the endoplasmic reticulum (ER) that maintains calcium levels and controls protein folding, but has recently been found at the cell surface, cytoplasm, and in the extracellular matrix. CRT participates in multiple physiological processes such as gene expression, the immune response, and cancer. Calreticulin has been shown to autoacetylate with the binding of preferred ligand 7,8-diacetoxy-4-methylcoumarin (DAMC). This project aims to develop a chemical biology approach to investigate importance of CRT acylating abilities on its nonendoplasmic reticulum functions by targeting the downstream substrates of CRT acetylation. Our goal was to use CRT to transfer a pentynoyl tag (using a novel ligand, DPeMC) to its substrates, which can then be used as a handle for protein identification. Molecular modelling using available data in the literature was used to approximate the binding interface between CRT and the acylation ligands. Molecular Operating Environment (MOE) software was used to perform sequence alignment, simulated annealing, positional refinement, and blind docking of acylated coumarins with the CRT model. Docking studies pointed to the P domain as the most thermodynamically and sterically favourable region for acylated coumarin binding with tryptophan residue 200 within the active site on CRT. Absorption and fluorescence spectra of all coumarin compounds in ethanol:PBS (1:9v/v) solution were investigated. Stern-Volmer quenching constant (KSV ), binding constant (K), and number of binding sites (n) of each coumarin compound with CRT was determined. Our studies demonstrated that acyl coumarin compounds bind to CRT using a dynamic quenching mechanism, bind to a single binding site on the P domain, and that the protein-ligand interaction is spontaneous and exothermic.

Institutional-cultural coherence and economic development: The case of the Spanish regions

We explore how cultural traits coherent with liberal institutions affect economic performance. The matching between cultural traits and institutions is what we refer to as cultural-institutional coherence. We study how cultural-institutional coherence influenced the paths followed by Spanish regions after Spain's liberal reforms in the 19th century. We argue that these liberal reforms brought important changes to Spain's institutions and contributed to inducing a major rearrangement in the distribution of economic development across the country's regions. This process favored regions with cultural traits that were more coherent with liberal institutions. We address endogeneity issues using the disparate political paths that the regions followed in their distant pasts. We characterize political paths in terms of Municipal autonomy in the Middle Ages, as well as Constraints on the executive in the early modern period which, we argue, are good instruments for these cultural traits.