Structural Functional Characteristics Research Articles

Phage-Displayed SH2 Domain Libraries: From Ultrasensitive Tyrosine Phosphoproteome Probes to Translational Research.

Tyrosine phosphorylation is a critical regulator of cell signaling. A large fraction of the tyrosine phosphoproteome, however, remains uncharacterized, largely due to a lack of robust and scalable methods. The Src homology 2 (SH2) domain, a structurally conserved protein domain present in many intracellular signal-transducing proteins, naturally binds phosphorylated tyrosine (pTyr) residues, providing an ideal scaffold for the development of sensitive pTyr probes. Its modest affinity, however, has greatly limited its application. Phage display is an in vitro technique used for identifying ligands for proteins and other macromolecules. Using this technique, researchers have been able to engineer SH2 domains to increase their affinity and customize their specificity. Indeed, highly diverse phage display libraries have enabled the engineering of SH2 domains as affinity-purification (AP) tools for proteomic analysis as well as probes for aberrant tyrosine signaling detection and rewiring, and represent a promising class of novel diagnostics and therapeutics. This review describes the unique structure-function characteristics of SH2 domains, highlights the fundamental contribution of phage display in the development of technologies for the dissection of the tyrosine phosphoproteome, and highlights prospective uses of SH2 domains in basic and translational research.

Effect of the antibiotic tetracycline on structural-functional characteristics of coccolithophore Chrysotila sp. and the degree of its calcification

Coccolithophorids play a fundamental role in the marine carbon cycle, fixing inorganic carbon during photosynthesis and exporting CO2 during calcification. In the presented study, the toxic effect of tetracycline on coccolithophorids of Chrysotila sp. was evaluated and the possibility of removing the antibiotic from water using this microalga was investigated. Tetracycline at a concentration of 1–15 mg L−1 had no effect on the growth of Chrysotila sp. and at higher values (20–25 mg L−1) it stimulated the growth of the algae. As the concentration of tetracycline increased, a tendency to decrease the percentage of coccolith-covered cells in the culture was observed. At the same time, the growth of Chrysotila sp. was realized mainly at the expense of uncovered coccoliths cells, the number of covered cells changed insignificantly. Coccolith- covered and uncovered Chrysotila sp. cells showed different physiological responses to antibiotic addition. Calcified cells are more sensitive to tetracycline, which is expressed in an increase in their size and a decrease in granularity, a decrease in specific chlorophyll fluorescence and enzymatic (esterase) activity, and an increase in the production of reactive oxygen species. Reduction of cell calcification under exposure to pollutants is potentially dangerous by changes in the biogeochemical cycle of nutrient elements in the aquatic ecosystem.It is shown that the main mechanism of tetracycline removal from water is photodegradation. However, in the presence of Chrysotila sp. the rate of tetracycline degradation is significantly higher (by 7–15%) than in samples without algae.

Impact of defatting method on oat protein isolate structure-function characteristics

Oat (Avena sativa) is valued for its high protein content of 15–20% and potential health benefits. Oat also contains a notable lipid content, ranging from 6% to 10%, which can lead to rapid oxidation and rancidity, lowering product shelf life. Thus, defatting is imperative for the production of high-quality oat-based ingredients. This study focuses on evaluating the impact of various defatting techniques, including hexane-based defatting, supercritical carbon dioxide extraction, and supercritical carbon dioxide extraction with ethanol, on the structural and functional characteristics of oat protein isolate. Oat protein isolate was produced through alkaline extraction-isoelectric precipitation and assessed for its proximate composition, structural characteristics, encompassing protein profile, surface hydrophobicity, denaturation, and functional properties, including solubility, foaming capacity, and emulsification. Our results indicate that supercritical fluid methods are promising in their effectiveness in defatting oat flour although characteristics such as protein purity and solubility need improvement. Nevertheless, supercritical carbon dioxide defatting methods were found to yield oat protein with functional and structural properties closely comparable to the hexane-based method. In conclusion, given the environmental impacts associated with hexane, supercritical defatting methods can be further optimized and used as an eco-friendly alternative to conventional solvent-based fat extraction techniques.

Luminescent MOFs Based on Thiazolo[5,4-d]thiazole as a Chemosensor for the Detection of Environmental Contaminants

Luminescent metal-organic frameworks (LMOFs) are considered special candidates for the sensation and detection of particular analytes. Thiazolo[5,4-d]thiazoles (TTZs) are an ideal type of heterocycles for fluorophores with π-bridge moieties demonstrating structure-function characteristics. LMOFs with excellent sensing properties can be constructed by incorporating heterocyclic aromatic thiazolo[5,4-d]thiazole into the framework. This study has elaborated on LMOFs containing thiazolo[5,4-d]thiazole unit for the detection of environmental contaminants, such as toxic anions, aromatic compounds, and heavy metal ions.

Structure and Trophic Characteristics of Zooplankton Communities of the East Siberian Sea

Research on the structure and trophic characteristics of zooplankton communities of the East Siberian Sea (ESS) was performed within the program “Marine Ecosystems of the Siberian Arctic” during cruise 69 of the R/V Akademik Mstislav Keldysh. The material was collected on two quasimeridional transects conducted in the latitudinal range ~71°00′–75°30′ N from the inner shelf adjacent to the Indigirka and Kolyma outfalls to the outer shelf during September 5–9, 2017. The list of species and larger taxa, as well as their biomass and trophic characteristics, are presented, and the peculiarities of cross-shelf distribution in relation to the conditions of the pelagic environment are described. The obtained estimates of the mezoplankton biomass in the ESS are on the whole within the range typical of the rest of the Siberian Seas in summer–fall. It has been established that mezoplankton communities of the western and eastern ESS significantly differ in quantitative characteristics, the role of dominant species and taxonomic groups in biomass, grazing impact of mesoplankton on the phytoplankton biomass and production, and features of the cross-shelf distribution of these characteristics. The boundary between the communities with different structural functional characteristics is located approximately at 160°–163° E. A conclusion is made that analysis of climatic and seasonal changes in ESS mezoplankton should be examined with allowance for the principal differences between pelagic biotopes and communities of the western and eastern parts of the basin.

Reversible crowdedness of pH-responsive and host–guest active polymersomes: Mimicking µm-sized cell structures

The structure–function characteristics of isolated artificial organelles (AOs) in protocells are mainly known, but there are few reports on clustered or aggregated AOs. To imitate µm-sized complex and heterogeneous cell structures, approaches are needed that enable reversible changes in the aggregation state of colloidal structures in response to chemical, biological, and external stimuli. To construct adaptive organelle-like or cell-like reorganization characteristics, we present an advanced crosslinking strategy to fabricate clustered polymersomes as a platform based on host–guest interactions between azobenzene-containing polymersomes (Azo-Psomes) and a β-cyclodextrin-modified polymer (β-CD polymer) as a crosslinker. First, the reversible (dis)assembly of clustered Azo-Psomes is carried out by the alternating input of crosslinker and adamantane-PEG3000 as a decrosslinker. Moreover, cluster size dependence is demonstrated by environmental pH. These offer the controlled fabrication of various homogeneous and heterogeneous Azo-Psomes structures, including the size regulation and visualization of clustered AOs through a fluorescent enzymatic cascade reaction. Finally, a temperature-sensitive crosslinking agent with β-CD units can promote the coaggregation of Azo-Psomes mediated by temperature changes. Overall, these (co–)clustered Azo-Psomes and their successful transformation in AOs may provide new features for modelling biological systems for eukaryotic cells and systems biology.

Discussion on structure classification and regulation function of histone deacetylase and their inhibitor.

Epigenetic regulation of genes through posttranslational regulation of proteins is a well-explored approach for disease treatment, particularly in cancer chemotherapy. Histone deacetylases have shown significant potential as effective drug targets in therapeutic studies aiming to restore epigenetic normality in oncology. Besides their role in modifying histones, histone deacetylases can also catalyze the deacetylation of various nonhistone proteins and participate in the regulation of multiple biological processes. This paper provides a review of the classification, structure, and functional characteristics of the four classes of human histone deacetylases. The increasing abundance of structural information on HDACs has led to the gradual elucidation of structural differences among subgroups and subtypes. This has provided a reasonable explanation for the selectivity of certain HDAC inhibitors. Currently, the US FDA has approved a total of six HDAC inhibitors for marketing, primarily for the treatment of various hematological tumors and a few solid tumors. These inhibitors all have a common pharmacodynamic moiety consisting of three parts: CAP, ZBG, and Linker. In this paper, the structure-effect relationship of HDAC inhibitors is explored by classifying the six HDAC inhibitors into three main groups: isohydroxamic acids, benzamides, and cyclic peptides, based on the type of inhibitor ZBG. However, there are still many questions that need to be answered in this field. In this paper, the structure-functional characteristics of HDACs and the structural information of the pharmacophore model and enzyme active region of HDAC is are considered, which can help to understand the inhibition mechanism of the compounds as well as the rational design of HDACs. This paper integrates the structural-functional characteristics of HDACs as well as the pharmacophore model of HDAC is and the structural information of the enzymatic active region, which not only contributes to the understanding of the inhibition mechanism of the compounds, but also provides a basis for the rational design of HDAC inhibitors.

Role of the plant-specific calcium-binding C2-DOMAIN ABSCISIC ACID-RELATED (CAR) protein family in environmental signaling

Many signaling processes rely on information decoding at the plasma membrane, and membrane-associated proteins and their complexes are fundamental for regulating this process. Still many questions exist as to how protein complexes are assembled and function at membrane sites to change identity and dynamics of membrane systems. Peripheral membrane proteins containing a calcium and phospholipid-binding C2-domain can act in membrane-related signaling by providing a tethering function so that protein complexes form. C2 domain proteins termed C2-DOMAIN ABSCISIC ACID-RELATED (CAR) proteins are plant-specific, and the functional relevance of this C2 domain protein subgroup is just emerging. The ten Arabidopsis CAR proteins CAR1 to CAR10 have a single C2 domain with a plant-specific insertion, the so-called “CAR-extra-signature” or also termed “sig domain”. Via this “sig domain” CAR proteins can bind signaling protein complexes of different kinds and act in biotic and abiotic stress, blue light and iron nutrition. Interestingly, CAR proteins can oligomerize in membrane microdomains, and their presence in the nucleus can be linked with nuclear protein regulation. This shows that CAR proteins may play unprecedented roles in coordinating environmental responses and assembling required protein complexes to transmit information cues between plasma membrane and nucleus. The aim of this review is to summarize structure-function characteristics of the CAR protein family and assemble findings from CAR protein interactions and physiological functions. From this comparative investigation we extract common principles about the molecular operations that CAR proteins may fulfill in the cell. We also deduce functional properties of the CAR protein family based on its evolution and gene expression profiles. We highlight open questions and suggest novel avenues to prove and understand the functional networks and roles played by this protein family in plants.

Genome-wide analysis of bromodomain gene family in Arabidopsis and rice.

The bromodomain-containing proteins (BRD-proteins) belongs to family of 'epigenetic mark readers', integral to epigenetic regulation. The BRD-members contain a conserved 'bromodomain' (BRD/BRD-fold: interacts with acetylated-lysine in histones), and several additional domains, making them structurally/functionally diverse. Like animals, plants also contain multiple Brd-homologs, however the extent of their diversity and impact of molecular events (genomic duplications, alternative splicing, AS) therein, is relatively less explored. The present genome-wide analysis of Brd-gene families of Arabidopsis thaliana and Oryza sativa showed extensive diversity in structure of genes/proteins, regulatory elements, expression pattern, domains/motifs, and the bromodomain (w.r.t. length, sequence, location) among the Brd-members. Orthology analysis identified thirteen ortholog groups (OGs), three paralog groups (PGs) and four singleton members (STs). While more than 40% Brd-genes were affected by genomic duplication events in both plants, AS-events affected 60% A. thaliana and 41% O. sativa genes. These molecular events affected various regions (promoters, untranslated regions, exons) of different Brd-members with potential impact on expression and/or structure-function characteristics. RNA-Seq data analysis indicated differences in tissue-specificity and stress response of Brd-members. Analysis by RT-qPCR revealed differential abundance and salt stress response of duplicate A. thaliana and O. sativa Brd-genes. Further analysis of AtBrd gene, AtBrdPG1b showed salinity-induced modulation of splicing pattern. Bromodomain (BRD)-region based phylogenetic analysis placed the A. thaliana and O. sativa homologs into clusters/sub-clusters, mostly consistent with ortholog/paralog groups. The bromodomain-region displayed several conserved signatures in key BRD-fold elements (α-helices, loops), along with variations (1-20 sites) and indels among the BRD-duplicates. Homology modeling and superposition identified structural variations in BRD-folds of divergent and duplicate BRD-members, which might affect their interaction with the chromatin histones, and associated functions. The study also showed contribution of various duplication events in Brd-gene family expansion among diverse plants, including several monocot and dicot plant species.

Context-Sensitive Solution: concept, demand, and potential of the method for modernizing transportation planning

The Context Sensitive Solution, a terminology created in the early 2000s in the USA and still pending translation to Portuguese, configures a methodology to support promoting participation and inclusion of different actors in the transport planning processes. The approach is an alternative to the complex demand for contemporary transport planning. It has shown promising results in studies of urban roads for communities, mainly because it aims to serve users through compatibility with the surroundings, community, and environment. Although Context Sensitive Solution originated in the early 2000s and with proven maturity in projects involving interventions on highways and major avenues in a peri-urban environment in large North American cities, its dissemination has not yet reached the peak of its potential and demand. The growing complexity of the transport and territorial planning policies makes it imperative to study solutions compatible with demand that address the problem in a comprehensive, transparent and participatory manner. As a management tool, the Context Sensitive Solution considers the values ​​of stakeholders and the local community, in contrast to conventional practices of planning transport works that directly intervene in the urban space in which traditionally there is a lack of approaches that integrate local interests and values. In Brazil, the urban landscape's enormous dynamics and the city's structure's functional characteristics justify the academy's inclination to understand and adapt the Context Sensitive Solution to the local characteristics and desires. Notwithstanding the already established negative aspects such as the loss of connectivity, disruption in the local microeconomy, and encouraging a drop in security that impact the quality of life for the population bordering highways and significant avenues, there are also severe changes in the landscape, the natural flow of drainage, habitat segregation, noise, light and particulate matter pollution, as well as fauna mortality. Given this scenario, our manuscript introduces the concept of the Context Sensitive Solution and discusses its current demand and potential for use in planning and managing space nearby proposed or constructed critical linear infrastructure projects with the potential to interfere with the landscape and functions of urban locations. Furthermore, an in-depth literature review focused on the theme made it possible to know and measure the state of the art of the technique and identify the gains proposed by the method, for which situations there is a collaborative and holistic approach to the problem, and the Solution stands out.

MANAGEMENT OF STRUCTURAL FUNCTIONAL FEATURES OF SEMI-DESERT LANDSHAFTS OF KARABAKH AND MIL PLAIN

Relevance of the topic. The modern anthropogenic complexes formed in the semi-desert landscapes of the Karabakh and Mil plains during different historical periods are natural-anthropogenic territorial units controlled and regulated by humans, whose structural-functional characteristics and productivity are constantly kept under control. Anthropogenic effects should be in the center of special attention in the management of structural and functional features of semi-desert landscapes in Karabakh and Mil plains. Here, special attention is paid to the structure of the agro-irrigation landscapes of the area, the degree of change of the alluvial and delluvial plains, as well as to the soil types. Due to the semi-desert, dry-desert and various intrazonal landscapes of Karabakh and the Mil Plain, these issues should always be in the center of attention, as they affect the formation and development of agriculture in our republic. The geographical features, soil and climatic conditions of Karabakh and Mil Plain were studied, and the current state of irrigation systems of the region was analyzed in this article, Research methodology and methods. In addition to the natural soil resources of the mentioned area, the article provides information about the saline soils. Here, irrigation systems, which have a special place in irrigated agriculture, and the construction and importance of canals are analyzed. The hydrogeological conditions and humidity conditions of the area are especially mentioned. For this purpose, along with the geographical features of the studied area, statistical indicators on the current state of irrigation systems, scientific works on the subject were also used. The main scientific innovation of the research is that the anthropogenic complexes formed in the semi-desert landscapes of the Karabakh and Mil plains were extensively analyzed in the article as natural-anthropogenic territorial units controlled and regulated by humans, whose structural-functional characteristics and productivity are constantly kept under control. The main scientific result of the study. Modern anthropogenic complexes formed in the semi-desert landscapes of Karabakh and Mil plains during historical periods are natural-anthropogenic territorial units controlled and regulated by people, whose structural-functional characteristics and productivity are constantly kept under control. Systematic study of the Karabakh and Mil plains and preparation of recommendations to increase their productivity are of great importance in the socio-economic development of our country.

THE INFLUENCE OF SPERMINE AND CHLORHEXIDINE ON THE SURVIVAL, ELECTROKINETIC AND CYTOMORPHOLOGICAL CHARACTERISTICS OF HUMAN PROSTATE CANCER CELLS

Summary. Aim: to study the effects of spermine and the spermine oxidase inhibitor chlorhexidine, applied alone or in combination, on the viability, electrokinetic and structural-functional characteristics of human prostate cancer cells in vitro. Object and methods: Studies were conducted on cell cultures: differentiated androgen-dependent LNCaP cell line and low-differentiated androgen-independent DU-145 cell line. Cell survival was determined by the method of exclusion of the vital dye trypan blue by living cells. The electrokinetic parameters of the cells (ζ-potential and total surface charge density) were determined according to the Smoluchovsky and Quincke-Helmholtz equations. Morphological changes were assessed by light microscopy of fixed preparations of cells stained with hematoxylin and eosin. Results: The fact established by previous studies that spermine at a concentration of 1.5 mM exhibits a pronounced inhibitory effect on the growth of differentiated human prostate cancer cells of the LNCaP line, which consists in reducing their survival to 48.5 ± 1.5% compared to intact control, and when this factor is used in a concentration exceeding 5.0 mM – in their death. It was shown that poorly differentiated cells of the DU-145 line were significantly more resistant to its influence: their survival decreased to 56.0 ± 1.9% only under the influence of spermine at a concentration of 5.0 mM; a concentration of 10.0 mM caused complete cell death of both lines. The trend persisted in the case of chlorhexidine: under its influence at a concentration of 15.0 μM, the survival of cells of the hormone-dependent LNCaP line was 33.0 ± 1.5%, and the hormone-independent DU-145 cell line was 79.0 ± 2.5%. The combined use of spermine and chlorhexidine (0.6 mM and 3.2 µM, respectively) caused a strong cytotoxic effect in cells of the LNCaP line (survival 19.0 ± 1.2%), while cells of the DU-145 line maintained a fairly high rate (76.0 ± 2.1%) even with a significantly higher content of spermine (3.0 mM) and chlorhexidine (5.0 μM) in the culture medium. It was established that under the influence of chlorhexidine, the cells of both studied lines show an inversion of the sign of the surface electric charge, changing it from negative to positive under physiological conditions, just as it was shown in experiments with spermine on cells of the LNCaP line. Certain quantitative differences caused by the investigated compounds in the electrokinetic indicators of cells of hormone-dependent and hormone-independent lines were revealed. Cells of the DU-145 line under the influence of spermine, or simultaneously spermine and chlorhexidine, showed a typical apoptotic morphology: they rounded and separated from each other and the substrate, chromatin condensation, blurred contours of the surface membrane, nuclear fragmentation and the presence of apoptotic bodies were noted. Conclusions: Spermine in concentrations of 1.5-10.0 mM and chlorhexidine in concentrations of 10.0-30.0 μM, applied separately, have a cytotoxic effect on human prostate cancer cells of LNCaP and DU-145 lines in culture. Cytotoxic properties of spermine, chlorhexidine or their combination are significantly more pronounced when acting on the hormone-dependent LNCaP line cells than on the hormone-independent DU-145 line. Their combined use demonstrates a significantly higher cytotoxic effect on cells of the LNCaP line, which is not observed in the DU-145 cell line. Chlorhexidine, like spermine, causes an inversion of the surface charge in the studied cell lines, changing its sign from negative to positive. The revealed differences like changes in survival and electrokinetic parameters of LNCaP and DU-145 cells can be explained by the presence or absence of androgen binding receptors on their surface membrane. Cells of the DU-145 line under the influence of spermine, or at the same time spermine and chlorhexidine, go to the state of apoptosis, as well as cells of the LNCaP line when they are exposed to spermine.

Temperature-Dependent Structure–Function Properties of Bacterial Xylose Isomerase Enzyme for Food Applications: An In Silico Study

Xylose Isomerase (XI) is an intramolecular oxidoreductase enzyme and catalyzes the reversible conversion of ketoses and aldoses in addition to the bioconversion of ethanol from xylose in the production of bioethanol from hemicellulose. It has a broad range of industrial applications in the food and pharmaceutical sectors, particularly in the production of the sweetener high fructose corn syrup (HFCS). It is one of the most widely used industrial enzymes after protease. Taking this into consideration, four bacterial XI sources were selected based on growth temperature, i.e., psychrophile, mesophile, thermophile, and hyperthermophile, for analyzing Xylose Isomerase’s structure-function characteristics. It was found that thermophilic XI was structurally less stable than mesophilic and hyperthermophilic XI, whereas structural plasticity ran opposite towards mesophiles. The interaction of xylose isomerase (XI) with two ligands, namely Amino-2-Hydroxymethyl-Propane-1,3-Diol and (4R)-2-Methylpentane-2,4- Diol, was also studied. Mesophilic XI demonstrated better binding affinity with structurally stabilizing amino acids (Ala, Asp, Gly, Leu, and Arg). In comparison, Thermophilic XI showed nearly similar binding affinity with both Amino-2-Hydroxymethyl-Propane-1,3-Diol and (4R)-2-Methylpentane-2,4-Diol. The results of this investigation suggest that thermophilic XI, followed by mesophilic XI, would be the most appropriate for establishing process stability and sustainability in the food industry.

Genetic variants, clinical characteristics and outcomes of non-compaction cardiomyopathy

Aim. Evaluate clinical and structural-functional characteristics, including adverse events and outcomes, in patients with non-compact cardiomyopathy (NCM) with various genetic variants.Material and Methods. 51 unrelated patients with NCM were examined (mean age 37 [28; 47]; men (54.9%), women (45.1%)), observed for 7 to 211 months (in average 38 months). Clinical and instrumental examination included checkup, collection of individual and family history, ECG-12 registration, 24-hour Holter ECG monitoring, echocardiography, magnetic resonance imaging (MRI) of the heart with late contrast enhancement. The search for mutations in the coding sequences of 174 genes associated with cardiovascular pathology was carried out by high-throughput sequencing (NGS).Results and discussion. In 24 of 51 (47.1%) patients, 27 mutations of pathogenicity classes IV and V were detected, while in 21 (41.2%) patients, mutations were in the genes of sarcomeric proteins, of which 37.5% were in the MYBPC3 gene, 25.0% in the MYH7 gene, and in the TTN gene, leading to a shortened protein (TTNtv) – 33.3%, there is a mutation in the ACTC1 – 1 gene (4.2%). In 5.9% of patients, mutations were detected in genes encoding structural proteins and ion channel subunits. Two or more genetic variants were found in 10 out of 24 (41.7%) patients. No significant genetic variants were identified in 14 (27.4%) patients. Patients with mutations in the TTNtv gene were associated with severe systolic dysfunction, dilation of the left ventricle. Carriers of mutations in the MYBPC3 gene and several genetic variants were more likely to have adverse events and outcomes: progression of chronic heart failure (CHF), ventricular tachyarrhythmias, sudden cardiac death (SCD) with successful resuscitation, mortality. Patients with mutations in the MYH7 gene had no adverse outcomes.Conclusion. Comparative analysis showed that patients with NCM had the most severe form of the disease with significant clinical manifestations, episodes of clinical death with subsequent resuscitation and cardioverter defibrillator implantation in probands with mutations in TTNtv gene, mutations in the MYBPC3 gene or multiple genetic variants.

Optimizing the stability and electrical transport properties of CeNbO4+δ-based oxide ceramics by regulating oxygen ion content

CeNbO4+δ ceramics have attracted extensive research interest because of their unique mixed ion-electron transport characteristics and interesting structure-functional characteristics caused by the difference in oxygen ion content. Although the change of oxygen ion content brings rich redox properties, it also causes serious crystal transformation and abnormal electrical transport properties. In order to obtain stable structure and excellent electrical transport properties, the directional regulation of the oxygen ion content has been realized through introducing Al2O3 and high temperature aging. After 600 h of aging at 1073 K, the prepared composite ceramics not only obtain a stable structure without crystal transformation, but also show good negative temperature coefficient (NTC) thermistor characteristics in the temperature range of 473 K–1273 K, in which the linear fitting maximum Pearson's r of the relationship between lnρ and 1000/T can reach 99.97%. The proposed method provides a new thought for the design and application of high-temperature electronic ceramics.

Photorenewable Azobenzene Polymer Brush-Modified Nanoadsorbent for Selective Adsorption of LDL in Serum

The elevated concentration of low-density lipoprotein (LDL) is recognized as a leading factor of hyperlipidemia (HLP), and selective adsorption of serum LDL is regarded as a practical therapy. Based on the superior structure-function characteristics of stimuli-responsive materials, a photorenewable nanoadsorbent (SiO2@Azo@Gly) with high selectivity and reusability was developed using azobenzene as the functional ligand. Its principle was certified by the preparation of silicon nanoparticles with atom transfer radical polymerization (ATRP)-initiating groups via a sol-gel reaction and their subsequent grafting of azobenzene polymer brushes by surface-initiated ATRP, followed by modification with glycine. Immobilization of carboxylated azobenzene polymer brushes onto the nanoparticles endowed SiO2@Azo@Gly with high adsorption selectivity and reusability. The advanced nanoadsorbent exhibited excellent LDL adsorption capacity at about 27 mg/g and could be regenerated by illumination with high efficiency (circulations ≥ 5); this was further verified by transmission electron microscopy (TEM) and Fourier-transform infrared (FTIR) analysis. SiO2@Azo@Gly also demonstrated superior adsorption efficiency and selectivity in serum from HLP patients, the respective adsorption capacities of LDL, triglyceride, and total cholesterol were about 15.65, 24.48, and 28.36 mg/g, and the adsorption to high-density lipoprotein (cardioprotective effect) was only about 3.66 mg/g. Green regeneration of the nanoadsorbent could be achieved completely through a simple photoregeneration process, and the recovery rate was still 97.9% after five regeneration experiments.

Genetic variants, clinical characteristics and outcomes of non-compact cardiomyopathy

Aim: evaluate clinical and structural-functional characteristics, including adverse events and outcomes, in patients with noncompact cardiomyopathy (NCM) with various genetic variants.Material and Methods. 51 unrelated patients with NCM were examined (mean age 37 [28; 47]; men (54.9%), women (45.1%)), observed for 7 to 211 months (in average 38 months). Clinical and instrumental examination included checkup, collection of individual and family history, ECG-12 registration, 24-hour Holter ECG monitoring, echocardiography, magnetic resonance imaging (MRI) of the heart with late contrast enhancement. The search for mutations in the coding sequences of 174 genes associated with cardiovascular pathology was carried out by high-throughput sequencing (NGS).Results and discussion. In 24 of 51 (47.1%) patients, 27 mutations of pathogenicity classes IV and V were detected, while in 21 (41.2%) patients, mutations were in the genes of sarcomeric proteins, of which 37.5% were in the MYBPC3 gene, 25.0% in the MYH7 gene, and in the TTN gene, leading to a shortened protein (TTNtv) – 33.3%, there is a mutation in the ACTC1 – 1 gene (4.2%). In 5.9% of patients, mutations were detected in genes encoding structural proteins and ion channel subunits. Two or more genetic variants were found in 10 out of 24 (41.7%) patients. No significant genetic variants were identified in 14 (27.4%) patients. Patients with mutations in the TTNtv gene were associated with severe systolic dysfunction, dilation of the left ventricle. Carriers of mutations in the MYBPC3 gene and several genetic variants were more likely to have adverse events and outcomes: progression of chronic heart failure (CHF), ventricular tachyarrhythmias, sudden cardiac death (SCD) with successful resuscitation, mortality. Patients with mutations in the MYH7 gene had no adverse outcomes.Conclusion. Comparative analysis showed that patients with NCM had the most severe form of the disease with significant clinical manifestations, episodes of clinical death with subsequent resuscitation and cardioverter defibrillator implantation in probands with mutations in TTNtv gene, mutations in the MYBPC3 gene or multiple genetic variants.

PECULIARITIES OF PRODUCTION OF AGRICULTURAL PRODUCTS IN KARAKALPAKSTAN

The article focuses on the study of issues such as agro-ecological features of the Republic of Karakalpakstan, improvement of economic mechanisms for the development of family-based entrepreneurship in rural areas, study of theoretical and methodological problems related to sustainable economic development, effective use of specific features of the region and development of new approaches. Also, the result of agrarian reforms in the world and our country, the specific positive features, scale and possibilities of effective use of all forms of agribusiness: large, medium and small, to increase food resources in the agrarian sector of the economy, were studied. Therefore, it is necessary to have a deeper understanding of the social-economic nature of the concept of the family economy, its signs and structural-functional characteristics, and the laws of development, which are becoming more and more important for the development of our country as a subject of the market economy. Proposals and recommendations on expanding the participation of family farms in ensuring socio-economic stability in the country by increasing the income of the population in the village, reducing the level of unemployment, and growing the layer of middle owners are presented.

Structure-Functional Characteristics of the Svx Protein—The Virulence Factor of the Phytopathogenic Bacterium Pectobacterium atrosepticum

The Svx proteins are virulence factors of phytopathogenic bacteria of the Pectobacterium genus. The specific functions of these proteins are unknown. Here we show that most of the phytopathogenic species of Pectobacterium, Dickeya, and Xanthomonas genera have genes encoding Svx proteins, as well as some plant-non-associated species of different bacterial genera. As such, the Svx-like proteins of phytopathogenic species form a distinct clade, pointing to the directed evolution of these proteins to provide effective interactions with plants. To get a better insight into the structure and functions of the Svx proteins, we analyzed the Svx of Pectobacterium atrosepticum (Pba)—an extracellular virulence factor secreted into the host plant cell wall (PCW). Using in silico analyses and by obtaining and analyzing the recombinant Pba Svx and its mutant forms, we showed that this protein was a gluzincin metallopeptidase. The 3D structure model of the Pba Svx was built and benchmarked against the experimental overall secondary structure content. Structure-based substrate specificity analysis using molecular docking revealed that the Pba Svx substrate-binding pocket might accept α-glycosylated proteins represented in the PCW by extensins—proteins that strengthen the PCW. Thus, these results elucidate the way in which the Pba Svx may contribute to the Pba virulence.

Comparative In-silico Analysis of Structural and Functional Attributes of Microbial Lipases

Lipase is the third most demanding enzyme group and is a major component of fat metabolism. It is omnipresent in nature. Microbial lipases are highly specific and economically efficient enzymes. They have applications in a variety of industries. In this study, the computational result elucidates structural and functional attributes of eight selected lipases from Uniprot. Primary, secondary, and tertiary structures obtained from Swiss and Profunc are analyzed. Further, they are validated with the help of Saves Server. COACH and COFACTOR is used for functional analysis. Lastly, phylogenetic tree is developed using MegaX software. Our in-silico analysis predicted lipases as alpha-beta-gamma protein with different ligand binding sites at different amino acid residue positions. Furthermore, they exhibited almost similar functional traits like catalytic activity and hydrolase activity. Overall, this study provides an insight into structural-functional characteristics of different lipases of microbial origin.