Analysis Of Complexes Research Articles

Recommendations for Accurate Lipid Annotation and Semi-absolute Quantification from LC-MS/MS Datasets.

Recent developments in LC-MS instrumentation and analytical technologies together with bioinformatics tools supporting high-throughput processing of large omics datasets significantly enhanced our capabilities and efficiency of identification and quantification of lipids in diverse biological materials. However, each biological matrix is characterized by its unique lipid composition, thus requiring optimization of analytical and bioinformatics workflows for each studied lipidome. Here, we describe an integrated workflow for deep lipidome profiling, accurate annotation, and semi-absolute quantification of complex lipidomes based on reversed phase chromatography and high resolution mass spectrometry. This chapter provides details on selection of the optimal extraction protocol, acquisition of LC-MS/MS data for accurate annotation of lipid molecular species, and design of lipidome-specific mixtures of internal standards to assist quantitative analysis of complex, native lipidomes.

Clinical analysis of biomaterial-silicone keel complex in the vocal folds adhesion treatment

Objective:To retrospectively analyze the clinical effect of biomaterial combined with silicone keel technology in the prevention and treatment of vocal folds adhesion. Methods:The basic data, perioperative conditions and prognosis of 21 cases of vocal folds adhesion treated by biofilm-silicone keel complex were retrospectively analyzed in Huashan Hospital Fudan University. Results:A total of 21 patients were enrolled in this study（19 males（90.5%）, 2 females（9.5%）. Among these patients, 18 cases of early glottic laryngeal carcinoma（T1b）, 1 case of bilateral vocal folds leukoplecta and 2 cases of postoperative vocal folds adhesion. No accidental rupture of the silicone keel occurred during perioperative period, and the silicone keel was removed in 22.4±2.6 days. All patients were reviewed after removing the silicone keel, the overall effective rate was 90.5%（19/21）. Postoperative complications occurred in 5 patients（1 laryngeal infection, 4 granulation tissue hyperplasia）, all of whom were cured after conservative treatment. Conclusion:This study explored the feasibility of biomaterial in the treatment of vocal folds adhesion. The biomaterial-silicone keel complex technology is simple to operate and has effect on the prevention of vocal folds adhesions, which is worth of clinical promotion.

Radiochemistry and Complex Formation of the Cyclen-Derived Chelator DOTI-Me with Mn2+, Cu2+, Zn2+, Ga3+, In3+, Tb3+, and Lu3.

In this work, we describe the complex formation and radiochemistry of the cyclen-based chelator DOTI-Me bearing four methylimidazole arms. Radiolabeling properties were evaluated for 52gMn, 64Cu, 68Ga, 111In, 161Tb, and 177Lu, and DOTI-Me showed distinct differences to the structurally related H4DOTA. While radiochemical conversions (RCCs) for 52gMn and 111In were comparable to those of H4DOTA, DOTI-Me was not suited for 68Ga. Conversely, quantitative RCCs were achieved for 64Cu at ambient temperature, while elevated temperatures were required for complexation with H4DOTA. For 161Tb and 177Lu, good but not quantitative RCCs were obtained with DOTI-Me. With the exemption of 68Ga3+, radiolabeled complexes showed high stability in ligand challenge experiments and in human serum. X-ray analysis of the nonradioactive complexes revealed the formation of 8-coordinate Mn2+ and In3+ DOTI-Me complexes. Cu2+ adopted a unique distorted square-pyramidal 2 + 3 with the neutral DOTI-Me ligand and a Jahn-Teller distorted 4 + 2 coordination geometry for the diprotonated H2DOTI-Me2+ cation, respectively. For Zn2+, the complex with HDOTI-Me+ showed a distorted 4 + 3 pentagonal bipyramidal geometry. Summarizing, the ligand DOTI-Me may be an interesting alternative to H4DOTA for 52gMn, 64Cu, 111In, 161Tb, and 177Lu, covering diagnostic as well as therapeutic radionuclides. Further studies of targeted radiopharmaceuticals based on the DOTI-Me scaffold in combination with the set of radiometals presented herein are thus warranted.

Conjugated 1,3-diketone calix[4]arenes: synthesis, complexation and structure-dependent sensitizing of Eu3+-luminescence

This work presents new type of bis-1,3-diketone calix[4]arene derivatives, in which the chelate groups are directly conjugated through the carbonyl carbon atom with aromatic fragments of calix[4]arene, and their lower rims bear four propoxy groups or pairs of hydroxy and propoxy groups. Tetrapropoxy-calix[4]arene is synthesized by acylation of magnesium acetophenone enolates with calix[4]arene-based 1-acylbenzotriazoles, and the dipropoxy analogue is obtained by bromination of bis(chalcone)-calix[4]arene, followed by methanolysis and hydrolysis. Significant conjugation of 1,3-diketo groups with the π-system of calix[4]arene is revealed for both calixarenes. Analysis of complexes formed by the ligands using the UV–Vis and NMR diffusion methods in combination with DFT calculations makes it possible to identify differences in the modes of complex formation of di- and tetrapropoxy subsituted ligands. It is demonstrated that a more enhanced sensibilization of Eu3+-luminescence in complexes with dipropoxy-calix[4]arene compared to that for complexes with tetrapropoxy-counterpart correlates with the formation of a tetrameric structure, in which the binding of Eu3+ ions does not disturb the conjugation of 1,3-diketonate moieties with aromatic calix[4]arene fragments. This is quite different from the significant disturbance of conjugation during intramolecular bis-chelation of Eu3+ ion by 1,3-diketo groups of tetraalkyl subsituted ligand.

DockQ v2: improved automatic quality measure for protein multimers, nucleic acids, and small molecules.

It is important to assess the quality of modeled biomolecules to benchmark and assess the performance of different prediction methods. DockQ has emerged as the standard tool for assessing the quality of protein interfaces in model structures against given references. However, as predictions of large multimers with multiple chains become more common, DockQ needs to be updated with more functionality for robustness and speed. Moreover, as the field progresses and more methods are released to predict interactions between proteins and other types of molecules, such as nucleic acids and small molecules, it becomes necessary to have a tool that can assess all types of interactions. Here, we present a complete reimplementation of DockQ in pure Python. The updated version of DockQ is more portable, faster and introduces novel functionalities, such as automatic DockQ calculations for multiple interfaces and automatic chain mapping with multi-threading. These enhancements are designed to facilitate comparative analyses of protein complexes, particularly large multi-chain complexes. Furthermore, DockQ is now also able to score interfaces between proteins, nucleic acids, and small molecules. DockQ v2 is available online at: https://wallnerlab.org/DockQ.

Tailoring potential antigenic regions on pandemic SARS spike protein

Coronavirus-associated severe acute respiratory syndrome (SARS) pandemics have devastated lives, economies, and societies worldwide. Given the higher severity of the latter pandemic, the constant mutation, and vaccine escape, new and more dangerous pandemics could emerge. Therefore, it is imperative to identify conserved vaccine candidates for stable effectiveness in future pandemics. This study aimed to tailor potential, conserved peptide-based vaccine candidates for the upcoming Coronavirus pandemic based on the sequences of the spike protein of SARS-CoV-1 and SARS-CoV-2 viruses, using bioinformatic approaches. Peptide-based CD4+ T-cell epitopes derived from SARS proteomes were identified based on their predicted binding affinity to HLA-DRB1, one of the central molecules for the adaptive immune system. These epitopes were then assessed for conservation by sequence analysis of all pandemic-involved strains and variants. The epitopes were then evaluated and cross-checked for possible protection against the causative pathogens via potential uptake by B-cell receptors, the sustenance of sequence conservation for the future pandemic strain using data from population HLA-allele-typing studies, structural analysis of the spike-antibody complex and their contribution to the function of spike protein, respectively. As a result, selected vaccine candidates were projected to cover nearly 90% of the world's population with the combination of just four epitopes. The epitopes could be modified to adapt to future pandemic strains, improve antigenicity, or be used as booster immunization against the currently circulating SARS-CoV-2 variant. This study demonstrates that there is still room for improvement and promising discoveries in vaccine design to deter upcoming SARS pandemics.

Influence of Sodium Lauryl Sulfate Anionic Micelles on the Complex Equilibria of Divalent Metal Ions with Isoleucine Amino Acid

The main objective of the present investigation is the formation analysis of metal-ligand complexes of isoleucine with divalent calcium, magnesium and zinc metal ions in various concentrations of sodium dodecyl sulphate (0.0, 0.5, 1.0, 1.5, 2.0 and 2.5 percent w/v). To look into the impact of the concentration of negatively charged micelles, the parameters were changed and the possible chemical species of isoleucine that interact with the metal ions, are being studied. The experiment was performed using pH meter at 303 K using NaCl to keep ionic strength stable at 0.16 mol dm-3 in the presence of anionic surfactant sodium dodecyl sulphate (SDS). The determination of the correction factor was conducted via the computer program SCPHD. The computational software MINIQUAD75 is utilized to determine the stability constants of ligand-metal complexes through the analysis of titration data. Based on statistical features such as skewness, 2, kurtosis and crystallographic R-factor, the best fit to the complicated speciation was selected. The metal ions Ca (II), Mg (II) and Zn (II) formed complexes ML, ML2 and ML2H2 for Ca (II), Mg(II) and ML, ML2 and ML2H for Zn (II) through the complexation of isoleucine. In order to validate the accuracy of the final established model, deliberate defects were introduced into the relevant components.

Выбор рационального инструментария для анализа полифенолов цветков бессмертника песчаного и листьев артишока колючего в комплексе фармакологических исследований

Background: Pathology of the hepatobiliary system includes a heterogeneous group of diseases of the liver and biliary system caused by viral, bacterial and parasitic infections, neoplasms, toxic chemicals, including alcohol, nutritional errors, metabolic disorders and heart failure. One of the basic groups for pharmacological correction of this group of diseases is the use of hepatoprotectors, drugs that have a predominantly selective effect on the liver. The active ingredient of most plant hepatoprotectors are flavonoids and hydroxycinnamic acids. The most popular plants – hepatoprotectors containing these active substances include – artichoke prickly (Cynara scolymus (L.)) and sandy everlasting (Helichrysum arenarium (L.) Moench), a plant with choleretic action, also capable of hepatoprotective activity. The aim of the study: Development and comparative characterisation of methods for the analysis of polyphenolic composition of sandy everlasting flowers and artichoke leaves in complex pharmacological studies using HPLC and capillary electrophoresis methods. Materials and methods: The sum of polyphenolic compounds was subjected to chromatographic separation in gradient elution mode. Capillary electrophoresis was carried out in a variant of micellar electrokinetic chromatography (MEKC). The buffer solution used was a mixture of: borate buffer 20 mM (pH - 9.3) – beta-cyclodextrin 20 mM – ethyl alcohol (10:10:5). Results: The electrophoregrams of the separation of artichoke leaf extract by the MECC method showed the presence of 7 components belonging to oxycinnamic acids and flavonoids. The dominant ones are chlorogenic acid and luteolin7-glucoside. Similar results were obtained by the HPLC method. The electrophoregram of immortelle flower extract shows 9 components, of which the dominant one belongs to isosalipurposide. Chromatographic analysis of sandy everlasting flower extract showed the presence of the same components. Conclusion: The results of the analysis of the polyphenolic complex of artichoke leaves and sandy everlasting flowers by capillary electrophoresis agree with the data obtained by HPLC chromatography. This allows us to conclude that the MECC method allows the identification and quantification of each component in artichoke leaves and HPLC chromatography flowers along with HPLC. Moreover, the performance of the analysis by CE is more economically feasible than HPLC, since it does not require the use of solvents for the mobile phase and the availability of a set of columns.

Synthesis, Structural Determination, DFT Calculation and Biological Evaluation Supported by Molecular Docking Approach of Some New Complexes Incorporating (E)‐N'‐(3,5‐di‐Tert‐Butyl‐2‐Hydroxybenzylidene) Isonicotino Hydrazide Ligand

ABSTRACTThe synthesis and structural analysis of complexes derived from (E)‐N′‐(3,5‐di‐tert‐butyl‐2‐hydroxybenzylidene) isonicotino hydrazide (ITB ligand) were examined using multiple analytical techniques. These techniques included TGA, decomposition point determination, elemental analysis (CHN), spectroscopic (IR, NMR, mass spectrometry) analysis, magnetic susceptibility, conductivity, as well UV–Vis spectrum analysis, along with theoretical studies. Molar conductance values indicated that the Cd (II), Co (II), Cu (II), Ni (II), and Zn (II) complexes are non‐electrolytes in fresh DMSO solutions, with conductance values ranging from 8.5 to 14.35 Ω−1 cm2 mol−1. IR spectra suggested which the ligand coordinates through the metal ions in a tridentate fashion, utilizing the (N & O) donor sites from the (CN & CO & CO) groups in the hydroxybenzylidene moiety. Analytical data from solution complexation, job's method suggested a 1:1 (metal:ligand) molar ratio. The stability order of the complexes was determined as ITBCo > ITBCu > ITBNi > ITBZn > ITBCd, consistent with the stability constant (Kf) values. The pH profile indicated that the studied complexes exhibit stability upon a wide pH scale, typically between (pH = 4:10). Magnetic and electronic spectral analyses helped deduce the ligand coordination abilities and the geometric structures of the complexes. In vitro (antimicrobial & anticancer) performances of the studied complexes were tested versus various (microbial strains & cancer cell lines), revealing higher activity in the chelates assessed to the free (ITB) ligand. The antioxidant potential was also assessed using the DPPH assay. Finally, molecular docking was performed toward estimate the binding efficiency between various protein receptors and the compounds, with results aligning with the biological investigations.

Synthetic, Electrochemical, DFT, and Synchrotron X-ray Charge-Density Studies on Oxo-centered Triruthenium Clusters Supported by Electron-Withdrawing Carboxylates.

We herein report the synthesis, characterizations, and synchrotron X-ray charge-density studies of oxo-centered triruthenium(II,III,III) clusters [Ru3O(CHCl2COO)6(py)3] (1) and [Ru3O(CHCl2COO)6(CO)(py)2] (2) (py = pyridine). Dichloroacetate was chosen for its large scattering factor of the Cl atom, and its electron-withdrawing nature results in significant stabilization of the targeted lower-valent Ru3II,III,III state in the cluster framework. Multipole analysis revealed that the difference in electron populations between two crystallographically independent Ru centers is small for 1 (Δ = 0.30 e) but large for 2 (Δ = 1.46 e). Remarkable differences between 1 and 2 are also found in their static deformation density maps; substantial local charge depletion was found around the central μ3O atom for 1, which is less pronounced for 2. According to the topological characterization of Ru-μ3O bonds associated with the bond critical point, bcp, the electron density, ρbcp, is in the range of 0.79-0.89 e Å-3, and the total energy density, Hbcp, is in the range of -0.21 to -0.05 hartree Å-3. These findings represent the first charge-density distribution analysis of mixed-valence multinuclear Ru complexes including comparison between 3d and 4d transition-metal systems.

Method Development for Analysis of Cyclodextrin Inclusion Complexes with HPLC

Cyclodextrin inclusion complexes have been widely used in the pharmaceutical industry to improve drug solubility and bioavailability. Analysis of these complexes using HPLC requires the development of appropriate and validated methods. To analyze and compare various HPLC methods used for the analysis of cyclodextrin inclusion complexes, and to identify challenges and trends in method development. A literature review was conducted of articles published in the last 10 years, focusing on HPLC methods for the analysis of cyclodextrin inclusion complexes. Parameters compared included column type, mobile phase composition, flow rate, and detection method. The majority of studies used C18 columns with varying lengths and particle sizes. The composition of the mobile phase varied, reflecting the diversity of properties of the complexes analyzed. The flow rate was generally 1.0 mL/min, with the exception of the HPLC/MS method. Detection methods included UV-Vis, PDA, fluorescence, and mass spectrometry. The main challenges included the dynamic equilibrium of the complexes and stability during analysis HPLC method development for the analysis of cyclodextrin inclusion complexes requires optimization of various parameters to overcome specific challenges. Future trends are towards the use of advanced technologies such as UHPLC and high-resolution mass detection.

Size-based spectrophotometric analysis of the Polana-Eulalia Complex

The Polana-Eulalia Complex (PEC) is an Inner Main Belt, C-complex asteroid population that may be the source of the near-Earth asteroid spacecraft mission targets (101955) Bennu and (162173) Ryugu. Here, we report a size-based investigation of the visible (VIS; 0.47 —0.89 μm) spectrophotometric slopes of the PEC's constituent families, the “New Polana” and Eulalia Families. Using two releases of the Sloan Digital Sky Survey's Moving Object Catalog as well as the 3rd data release of the Gaia catalog, we present evidence of size-based slope variability within each family. We find that Eulalia family members exhibit lower average slopes than Polana family members in all catalogs' samples, particularly for objects <9 km in diameter. We are unable to conclude that VIS slope distinguishability between the families is statistically significant, but we explore a potential cause of the bulk slope differences between the PEC families, in addition to providing commentary on size-slope trends generally.

Proteomic analysis of the SMN complex reveals conserved and etiologic connections to the proteostasis network.

Molecular chaperones and co-chaperones are highly conserved cellular components that perform a variety of duties related to the proper three-dimensional folding of the proteome. The web of factors that carries out this essential task is called the proteostasis network (PN). Ribonucleoproteins (RNPs) represent an underexplored area in terms of the connections they make with the PN. The Survival Motor Neuron (SMN) complex is an assembly chaperone and serves as a paradigm for studying how specific RNAs are identified and paired with their client substrate proteins to form RNPs. SMN is the eponymous component of a large complex, required for the biogenesis of uridine-rich small nuclear ribonucleoproteins (U-snRNPs), that localizes to distinct membraneless organelles in both the nucleus and cytoplasm of animal cells. SMN protein forms the oligomeric core of this complex, and missense mutations in the human SMN1 gene are known to cause Spinal Muscular Atrophy (SMA). The basic framework for understanding how snRNAs are assembled into U-snRNPs is known. However, the pathways and mechanisms used by cells to regulate their biogenesis are poorly understood. Given the importance of these processes to normal development as well as neurodegenerative disease, we set out to identify and characterize novel SMN binding partners. We carried out affinity purification mass spectrometry (AP-MS) of Drosophila SMN complexes using fly lines exclusively expressing either wildtype or SMA-causing missense alleles. Bioinformatic analyses of the pulldown data, along with comparisons to proximity labeling studies carried out in human cells, revealed conserved connections to at least two other major chaperone systems including heat shock folding chaperones (HSPs) and histone/nucleosome assembly chaperones. Notably, we found that heat shock cognate protein Hsc70-4 and other HspA family members preferentially associated with SMA-causing alleles of SMN. Hsc70-4 is particularly interesting because its mRNA is aberrantly sequestered by a mutant form of TDP-43 in mouse and Drosophila ALS (Amyotrophic Lateral Sclerosis) disease models. Most important, a missense allele of Hsc70-4 (HspA8 in mammals) was recently identified as a bypass suppressor of the SMA phenotype in mice. Collectively, these findings suggest that chaperone-related dysfunction lies at the etiological root of both ALS and SMA.

Structural Insights into the Substrate Recognition and Catalytic Mechanism of a GH16 βκ-Carrageenase from Wenyingzhuangia fucanilytica.

Understanding the substrate specificity of carrageenases has long been of interest in biotechnology applications. So far, the structural basis of the βκ-carrageenase that hydrolyzes furcellaran, a major hybrid carrageenan, remains unclear. Here, the crystal structure of Cgbk16A_Wf, as a representative of the βκ-carrageenase from GH16_13, was determined, and the structural characteristics of this subfamily were elucidated for the first time. The substrate binding mode was clarified through a structure analysis of the hexasaccharide-bound complex and molecular docking. The binding pocket involves a conserved catalytic motif and several specific residues associated with substrate recognition. Functions of residues R88, E290, and E184 were validated through site-directed mutagenesis. Comparing βκ-carrageenase with κ-carrageenase, we proposed that their different substrate specificities are partly due to the distinct conformations of subsite -1. This research offers a comprehensive understanding of the recognition mechanism of carrageenases and provides valuable theoretical support for enzyme modification and carrageenan oligosaccharide preparation.

Autoantibody mediated deficiency of IL-36-receptor antagonist in a subset of patients with psoriasis and psoriatic arthritis

ObjectivePsoriatic arthritis (PsA) is known as a seronegative form of spondylarthropathy. The interleukin-36 cytokine family may have a major role in disease pathogenesis and particularly the related cutaneous manifestations. In light of our recent observations on (transient) autoantibody phenotypes neutralizing endogenous anti-inflammatory receptor antagonists (progranulin, IL-1Ra) in different inflammatory conditions, we set out to investigate the potential role of such antibodies targeting IL-36 cytokine family members in PsA and psoriasis without arthritic manifestations (Pso). MethodsIn the present study we screened for hypothetic autoantibodies against the anti-inflammatory mediators IL-36 receptor antagonist (IL-36Ra) and anti-inflammatory IL-38 in PsA, Pso and inflammatory and healthy controls. Serum samples of patients with PsA (n = 254), Pso (n = 100), systemic lupus erythematosus (SLE, n = 50), rheumatoid arthritis (RA, n = 100), ulcerative colitis (UC, n = 50), Crohn´s disease (CD, n = 50), and healthy controls (n = 237) were screened for autoantibodies against IL-36Ra and IL-38 as well as IL-36Ra levels by ELISA. Biochemical analysis for immune complexes and atypic protein isoforms as well as IL-36 signaling reporter assays were performed. ResultsAnti-IL-36Ra antibodies were detected in five out of 100 (5.0 %) patients with Pso, in 12 of 254 (4.72 %) patients with PsA and in one of 50 (2 %) patients with CD, but in none of the other investigated inflammatory or healthy controls. The IL-36Ra autoantibodies belonged to the IgG1 subclass and their titers ranged between 1:200 to 1:1600. They resulted in immune-complex formation, depletion of serum IL-36Ra levels and were functional in terms of facilitating unrestricted IL-36 signaling. ConclusionIL-36Ra autoantibodies were found in subgroups of patients with Pso and PsA and may drive respective pathology.

Preparation of Polyclonal Antibodies to Barley Granule-Bound Amylopectin Synthase Ia and Their Application in the Characterization of Interacting Proteins

The production of amylose is facilitated by granule-bound starch synthase (GBSS). Despite its importance, the specific protein interactions involving barley grain-bound starch synthase Ia (HvGBSSIa) remain poorly understood. To elucidate this, we engineered a pET-32a-HvGBSSIa prokaryotic expression vector for specific expression in E. coli Rosetta cells. A rabbit anti-HvGBSSIa polyclonal antibody was generated and employed to enrich HvGBSSIa-binding proteins from barley grains through immunoprecipitation. The isolated complexes were then resolved through SDS-PAGE, and the constituent proteins were identified using mass spectrometry coupled with database searches. Our results confirmed the successful preparation of a highly specific polyclonal antibody against HvGBSSI. Furthermore, differential expression of HvGBSSIa was assessed across various barley tissues and developmental stages of the grain, revealing peak expression at 25 days post-flowering. Proteins interacting with HvGBSSIa, including sucrose synthase and starch branching enzyme, were identified through co-immunoprecipitation. This study lays the groundwork for further detailed analyses of the HvGBSSIa protein complex in barley.

Synthesis, Characterization and Antimicrobial Analysis of Nickel and Cobalt Complexes of Condensates of Salicylaldehyde and 2-Hydroxy Aniline

This study on the synthesis, characterization and antimicrobial analysis of Nickel and Cobalt complexes of condensates of salicylaldehyde and 2-hydroxy aniline constitutes an attempt towards the development of new molecular compounds that could destroy the barrier of resistance of pharmaceutical products. The ligands of 2-phenyliminomethylphenol (PMP) and 2,2-hydroxy benzylidene aminophenol (HAP) were first prepared by separately reacting Aniline with Salicylaldehyde on the one hand, and 2-aminophenol with Salicylaldehyde on the other hand. The unmixed metal complexes were prepared by reacting either of 0.29 mmol 2-phenylimino methyl phenol ligand with the metal salt or 0.29 mmol 2,2-hydroxybenzylideneaminophenol ligand with the metal salt while the mixed metal complexes were prepared by addition of equimolar amount of ligands of 2-phenyliminomethylphenol and 2,2-hydroxybenzylideneaminophenol into the metal salt. The molecular structures of the ligands and their complexes have been determined and characterized using GC-MS, FTIR, UV-Vis, 1H-NMR, and X-ray diffraction techniques. The melting point and solubility of the ligands and synthesized complexes were equally determined. Antimicrobial studies were carried out with ligands PMP and HAP and the metal complexes using clinical isolates of Gram Positive Bacteria (Staphylococcus aureus and Bacillus substilis), Gram Negative Bacteria (Escherichia coli and Pseudomonas aeruginosa) and Fungi (Candida albicans and Aspergillus niger). All complexes and ligands were found to be soluble in dimethylsulfoxide (DMSO). Asymmetric Octahedral geometry is observed for Nickel (II) and Cobalt (II) complexes with PMP, HAP, and the mixed ligands. A bidentate ligand is coordinated to metal ions through oxygen atoms of carbonyl groups and nitrogen atoms of two imine groups for Nickel (II) and Cobalt (II) complexes. The findings from the XRD pattern indicate that the ligand and metal complexes are crystalline with a high crystallite size of 119.23nm to 638.67nm. The FTIR spectra for 2-phenyliminomethylphenol (PMP) showed IR absorption band at 1569.2 cm-1 suggesting the stretching vibration of the C=C bond in the benzene rings, while the bands at 1613.9 cm-1 indicated the =C-N stretching in the benzene ring. The complexes showed electronic spectra which suggest that energy was absorbed in the ultraviolet/visible region, producing changes in the electronic energy of the compound and resulting from the transition of valence electrons in the complexes. The XRD findings reveal that the crystal formed by the ligands and their respective complexes are large. The ligands were found to be larger in size than the complexes and this could be due to the complexation reactions. The X-ray diffractograms of the metal complexes produced good intense peaks that suggest high crystallinity. The ligand of 2-phenyliminomethylphenol (PMP) and 2,2-hydroxy benzylidene aminophenol (HAP) showed partial inhibitory action on the clinical isolates of Gram Postive, Gram Negative and zero inhibitory effect on the fungi while the divalent metal complexes of both mixed and unmixed ligands exhibited either stronger or strongest inhibition. The study concludes that the synthesized ligands and their metal complexes are purely crystalline as revealed by the chemical analysis, exhibited inhibitory actions on Gram Positive, Gram Negative and fungi species.

Structural basis for antibody-mediated NMDA receptor clustering and endocytosis in autoimmune encephalitis.

Antibodies against N-methyl-D-aspartate receptors (NMDARs) are most frequently detected in persons with autoimmune encephalitis (AE) and used as diagnostic biomarkers. Elucidating the structural basis of monoclonal antibody (mAb) binding to NMDARs would facilitate the development of targeted therapy for AE. Here, we reconstructed nanodiscs containing green fluorescent protein-fused NMDARs to label and sort individual immune B cells from persons with AE and further cloned and identified mAbs against NMDARs. This allowed cryo-electron microscopy analysis of NMDAR-Fab complexes, revealing that autoantibodies bind to the R1 lobe of the N-terminal domain of the GluN1 subunit. Small-angle X-ray scattering studies demonstrated NMDAR-mAb stoichiometry of 2:1 or 1:2, structurally suitable for mAb-induced clustering and endocytosis of NMDARs. Importantly, these mAbs reduced the surface NMDARs and NMDAR-mediated currents, without tonically affecting NMDAR channel gating. These structural and functional findings imply that the design of neutralizing antibody binding to the R1 lobe of NMDARs represents a potential therapy for AE treatment.

Features of Distance Educational Technologies within the Framework Implemented by the Federal State Educational Standard

This article discusses the main normative documents regulating the forms and levels of professional training of students. Special attention is paid to the features of distance learning technologies (DOT) implemented as part of correspondence education at the agrarian University. The purpose of the research article is the application of new educational technologies in higher education. Research methodology and methods: theoretical analysis and descriptive method, including methods of comparative analysis of developed materials. In the course of this work, a comparative analysis of educational and methodological complexes of disciplines developed by the teaching staff was carried out. The results of the study. The university has developed an approximate structure of methodological materials, which includes an educational and methodological manual, funds of evaluation tools and additional educational and methodological materials. The approximate structure of the lesson in blocks is revealed: organizational, student and certification. Conclusion. Based on the studied materials, a generalizing conclusion can be drawn. The developed regulatory framework clearly regulates the organization and procedure for conducting distance learning.

Employing Hexahydroquinolines as PfCDPK4 Inhibitors to Combat Malaria Transmission: An Advanced Computational Approach.

Existing antimalarial drugs primarily target blood-stage parasites, but there is a need for transmission-blocking drugs to combat malaria effectively. Plasmodium falciparum Calcium-dependent Protein Kinase 4 (CDPK4) is a promising target for such drugs. This study employed advanced in silico analyses of hexahydroquinolines (HHQ) derivatives to identify PfCDPK4 inhibitors capable of disrupting malaria transmission. Structure-based virtual screening (SBVS) was employed to discover HHQ derivatives with the highest binding affinities against the 3D structure of PfCDPK4 (PDB 1D: 4QOX). Interaction analysis of protein-ligand complexes utilized Discovery Studio Client, while druglikeness and ADMET properties were assessed using SwissADME and pkCSM web servers, respectively. Quantum mechanical calculations of the top hits were conducted using density functional theory (DFT), and GROMACS was employed to perform the molecular dynamics (MD) simulations. Binding free energy was predicted using the MMPBSA.py tool from the AMBER package. SBVS identified ten best hits possessing docking scores within the range of -11.2 kcal/mol and -10.6 kcal/mol, surpassing the known inhibitor, BKI-1294 (-9.9 kcal/mol). Among these, 4-[4-(Furan-2-carbonyl)piperazin-1-yl]-1-(naphthalen-2-ylmethyl)-2-oxo-4a,5,6,7,8,8a-hexahydroquinoline-3-carbonitrile (PubChem ID: 145784778) exhibited the highest binding affinity (-11.2 kcal/mol) against PfCDPK4. Comparative analysis of this compound with BKI-1294 using advanced computational approaches demonstrated competitive potential. These findings suggest the potential of 4-[4-(Furan-2-carbonyl)piperazin-1-yl]-1-(naphthalen-2-ylmethyl)-2-oxo-4a,5,6,7,8,8a-hexahydroquinoline-3-carbonitrile as a promising PfCDPK4 inhibitor for disrupting malaria transmission. However, further experimental studies are warranted to validate its efficacy and safety profile.