Conformational Studies Research Articles

Designing a new alginate-fibrinogen biomaterial composite hydrogel for wound healing

Wound healing is a complex process and rapid healing necessitates a proper micro-environment. Therefore, design and fabrication of an efficacious wound dressing is an impressive innovation in the field of wound healing. The fabricated wound dressing in this scenario was designed using a combination of the appropriate coagulating and anti-bacterial materials like fibrinogen (as coagulating agent), nisin (as anti-bacterial agent), ethylenediaminetetraacetic acid (as anti-bacterial agent), and alginate (as wound healing agent). Biophysical characterization showed that the interaction of fibrinogen and alginate was associated with minor changes in the secondary structure of the protein. Conformational studies showed that the protein was structurally stable at 42 °C, is the maximum temperature of the infected wound. The properties of the hydrogel such as swelling, mechanical resistance, nisin release, antibacterial activity, cytotoxicity, gel porosity, and blood coagulation were assessed. The results showed a slow release for the nisin during 48 h. Antibacterial studies showed an inhibitory effect on the growth of Gram-negative and Gram-positive bacteria. The hydrogel was also capable to absorb a considerable amount of water and provide oxygenation as well as incorporation of the drug into its structure due to its sufficient porosity. Scanning electron microscopy showed pore sizes of about 14–198 µm in the hydrogel. Cell viability studies indicated high biocompatibility of the hydrogel. Blood coagulation test also confirmed the effectiveness of the synthesized hydrogel in accelerating the process of blood clot formation. In vivo studies showed higher rates of wound healing, re-epithelialization, and collagen deposition. According to the findings from in vitro as well as in vivo studies, the designed hydrogel can be considered as a novel attractive wound dressing after further prerequisite assessments.

X marks the spot in autoimmunity

ABSTRACT Introduction Autoimmune diseases mostly affect females. Besides hormones, several factors related to chromosome X have been called in action to explain this sex predominance. Areas covered This paper provides an overview on the role of chromosome X (chrX) in explaining why females have higher susceptibility to autoimmunity. The work outlines some essential concepts regarding chrX inactivation, escape from chrX inactivation and the evolutionary history of chrX. In addition, we will discuss the concept of gene escape in immune cells, with examples related to specific X-linked genes and autoimmune diseases. Expert opinion There is growing evidence that many genes present on chrX escape inactivation, and some of them have significant immune-mediated functions. In immune cells of female individuals the escape of these genes is not constant, but the knowledge of the mechanisms controlling this plasticity are not completely understood. Future studies aimed at the characterization of these modifications at single-cell resolution, together with conformational 3D studies of the inactive X chromosome, will hopefully help to fill this gap of knowledge.

Symmetries of conformal correlation functions

A program of wide interest in modern conformal bootstrap studies is to numerically solve general conformal field theories, based on a critical assumption that the dynamics is encoded in the conformal four-point crossing equations and positivity condition. In this paper we propose and verify a novel algebraic property of the crossing equations which provides strong restriction for this program. We show for various types of symmetries $\mathcal{G}$, the crossing equations can be linearly converted into the $SO(N)$ vector crossing equations associated with the $SO(N)\ensuremath{\rightarrow}\mathcal{G}$ branching rules and the transformations satisfy positivity condition. The dynamics constrained by the $\mathcal{G}$-symmetric crossing equations combined with the positivity condition degenerates to the $SO(N)$ symmetric cases, while the non-$SO(N)$ symmetric theories are not directly solvable without introducing the $SO(N)$ symmetry breaking assumptions on the spectrum.

Characterization of a cytoplasmic 2-Cys peroxiredoxin from Citrus sinensis and its potential role in protection from oxidative damage and wound healing

In present work, the recombinant cytoplasmic 2-Cys peroxiredoxin from Citrus sinensis (CsPrx) was purified and characterized. The peroxidase activity was examined with different substrates using DTT, a non-physiological electron donor. The conformational studies, in oxidized and reduced states, were performed using circular dichroism (CD) and fluorescence measurement. The CD analysis showed higher α-helical content for reduced state of the protein. The thermal stability studies of CsPrx by Differential Scanning Calorimetry (DSC) showed that oxidized state is more stable as compared to the reduced state of CsPrx. In vitro studies showed that the CsPrx provides a protective shield against ROS and free radicals that participate in the degradation of plasmid DNA. The pre-treatment of 10 μM CsPrx provide almost 100% protection against peroxide-mediated cell killing in the Vero cells. CsPrx showed significant cell proliferation and wound healing properties. The superior morphology of viable cells and wound closure was found at 20 μM CsPrx treated for 12 h. The results demonstrated that CsPrx is a multifaceted protein with a significant role in cell proliferation, wound healing and protection against hydrogen peroxide-induced cellular damage. This could be the first report of a plant peroxiredoxin being characterized for biomedical applications.

Bootstrapping Nf=4 conformal QED3

We present the results of a conformal bootstrap study of the presumed unitary IR fixed point of quantum electrodynamics in three dimensions (${\mathrm{QED}}_{3}$) coupled to ${N}_{f}=4$ two-component Dirac fermions. Specifically, we study the four-point correlators of the $SU(4)$ adjoint fermion bilinear $r$ and the monopole of lowest topological charge ${\mathcal{M}}_{1/2}$. Most notably, the scaling dimensions of the fermion bilinear $r$ and the monopole ${\mathcal{M}}_{1/2}$ are found to be constrained into a closed island with a combination of spectrum assumptions inspired by the $1/{N}_{f}$ perturbative results as well as a novel interval positivity constraint on the next-lowest-charge monopole ${\mathcal{M}}_{1}$. Bounds in this island on the $SU(4)$ and topological $U(1{)}_{t}$ conserved current central charges ${c}_{J}$, ${c}_{J}^{t}$, as well as on the stress tensor central charge ${c}_{T}$, are comfortably consistent with the perturbative results. Together with the scaling dimensions, this suggests that a part of estimates from the $1/{N}_{f}$ expansion---even at ${N}_{f}=4$---provide a self-consistent solution to the bootstrap crossing equations, despite some of our assumptions not being strictly justified.

Structural and conformational studies of biased agonism through formyl peptide receptors.

G protein-coupled chemoattractant receptors are class A GPCRs that couple primarily to the Gi class of heterotrimeric G proteins. Initially identified for their abilities to mediate leukocyte chemotaxis, chemoattractant GPCRs such as the formyl peptide receptors (FPRs) have been known for their diverse cellular functions in response to a variety of agonists. Stimulation of FPR2, in particular, leads to ligand-dependent activation of proinflammatory signaling as well as anti-inflammatory and proresolving signaling. Recently, the structures of FPR2-Gi protein complexed with ligands of different compositions have been solved by crystallization and cryo-electron microscopy. Analysis of the structural data as well as molecular simulation has led to the findings that the FPR2 binding pocket is sufficiently large for accommodation of several different types of ligands but in different poses. This mini-review focuses on the structural and conformational aspects of FPR2 for mechanisms underlying its biased agonism.

Enantiopure β3-Trifluoromethyl-β3-homoalanine Derivatives: Coupling with Boc-Protected Amino Acids and Conformational Studies of Peptides in Solid State

AbstractThe use of enantiopure β3-trifluoromethyl-β3-alkyl β-amino acids for the design of peptides would contribute to drastically enhance peptide stability in vivo. Moreover, the steric hindrance generated by the substituents on the tetrasubstituted carbon adjacent to the nitrogen function coupled to the electron-withdrawing effect of the trifluoromethyl group is more likely to influence the 3D conformation of the peptide. Herein, we describe a short, scalable and robust method to synthesize N- and/or C-protected enantiopure (R)- and (S)-β3-trifluoromethyl-β3-methyl β-amino acid derivatives and liquid-phase coupling methods suitable for incorporation of Boc-protected amino acids into short α/β- and β-peptides. Conformational studies of some of these original peptides via X-ray diffraction analysis highlighted intraresidue C6 hydrogen bonds within trifluoromethylated amino acids.

Monoclonal Antibodies as Probes to Study Ligand-Induced Conformations of Troponin Subunits.

Striated muscle contraction and relaxation is regulated by Ca2+ at the myofilament level via conformational modulations of the troponin complex. To understand the structure–function relationship of troponin in normal muscle and in myopathies, it is necessary to study the functional effects of troponin isoforms and mutations at the level of allosteric conformations of troponin subunits. Traditional methodologies assessing such conformational studies are laborious and require significant amounts of purified protein, while many current methodologies require non-physiological conditions or labeling of the protein, which may affect their physiological conformation and function. To address these issues, we developed a novel approach using site-specific monoclonal antibodies (mAb) as molecular probes to detect and monitor conformational changes of proteins. Here, we present examples for its application in studies of two subunits of troponin: the Ca2+-binding subunit, TnC, and the tropomyosin-binding/thin filament-anchoring subunit, TnT. Studies using a high-throughput microplate assay are compared with that using localized surface plasmon resonance (LSPR) to demonstrate the effectiveness of using mAb probes to assess ligand-induced conformations of troponin subunits in physiological conditions. The assays utilize relatively small amounts of protein and are free of protein modification, which may bias results. Detailed methodologies using various monoclonal antibodies (mAbs) are discussed with considerations for the optimization of assay conditions and the broader application in studies of other proteins as well as in screening of therapeutic reagents that bind a specific target site with conformational and functional effects.

Theoretical study of the helical conformers and ECD spectra of 8-aminoquinoline polymers

In this study, the helical conformers and absorption spectra of three types of 8-aminoquinoline oligoamides were studied. The stable conformers of these oligoamides connected with chiral β-pinene at their terminals were searched, and their dominant conformers and corresponding Boltzmann statistical weights were obtained. The excitation energy and oscillator strength of the dominant conformers were calculated, and the UV and electronic circular dichroism (ECD) spectra were also simulated. β-pinene can form delocalized π-bonds at the C-terminal, which results in a strong R band for CQn. Furthermore, the degree of polymerization also affected the strength of the absorption band for all the oligoamides.

Recent advances in the application of nanobody technology: a review

As a malleable and novel tool for antigen recognition and modulation, nanobodies have the advantages of small size, easiness of expression, screening and modification, as well as high affinity and stability. Nanobodies are capable of recognizing more cryptic antigenic epitopes that are difficult to be recognized by traditional antibodies, making them increasingly used in the diagnosis and treatment of various diseases and assays. Nanobodies are also playing an irreplaceable role in the basic research. This review summarized the recent development of nanobodies and their derivatives in the detection of small molecules, pathogenic microorganisms and diagnosis of diseases, as well as in the fields of targeted therapies, cellular and molecular imaging. Broad prospects of nanobodies in the field of protein conformation studies were also reviewed.

New bis hydrazone: Synthesis, X-ray crystal structure, DFT computations, conformational study and in silico study of the inhibition activity of SARS-CoV-2

The aim of this work was to synthesize new bis hydrazone derived from benzil in good yield, namely: (1Z,2Z)-1,2-bis (3-Chlorophenyl Hydrazino) Benzil, encoded by 3-Cl BHB. The benzil (or 1,2-diphenyl ethanedione) reacts with 3-Cl phenyl hydrazine by reflux method using ethanol as solvent to obtain the target compound. The obtained product is depicted by UV–Vis, IR spectroscopy and XRD-crystals analysis. All various contacts intra and intermolecular found in 3-Cl BHB were determined by the X-ray diffraction technique performed on single crystals. On the other hand, the optimized geometric structure of 3-Cl BHB was computed by the DFT/B3LYP method with 6–31 G (d, p) level. So, the bond lengths and angles, frontier molecular orbitals (FMO), surface electrostatic potential of the molecule (MEP), global reactivity descriptors, Mulliken atomic charges, computed vibrational analysis and electronic absorption spectrum were determined to get a good understanding of the electronic properties and the active sites of 3-Cl BHB, then to compare them with experimental data. Additionally, a conformational study was carried out using the same method (DFT). The structure-activity relationships established through molecular docking studies showed that 3-Cl BHB structure strongly binds to the receptors Mpro (-8.90 Kcal/mol) and RdRp (-8.60 Kcal/mol) which confirm its inhibition activity against COVID-19.

Conformational, spectroscopic, electronic and Molecular docking Studies on 2-methoxy-4-methyl-5-nitropyridine: A potential bioactive agent

The molecular geometry, vibrational bands, electronic properties and NMR spectra of 2 methoxy 4 methyl 5 nitropyridine (MMNP) were studied using density functional theory (DFT) calculations. The MMNP molecule was optimized using the DFT/B3LYP approach with the cc-pVTZ basis set to acquire the stable geometry. The potential energy distribution (PED) simulation was used to assign the obtained vibrational wavenumbers of the MMNP molecule. The chemical shift of 13C and 1H NMR spectrum was derived using the Gauge-Invariant-atomic orbital (GIAO) approach using DMSO solution and compared with the observed shifts. To investigate the electronic absorption spectral features of the MMNP molecule, the UV-Vis spectrum was simulated and observed. The hyperconjugation and intramolecular charge transfer were predicted using FMO and NBO analysis. Mulliken atomic charge distribution, Molecular Electrostatic potential (MEP) surface and the local reactivity analysis were used to spot out the reactive sites of the MMNP molecule. Moreover, the MMNP molecule acts as a potent inhibitor against bladder cancer so that the title molecule may be used in the drug designing for the treatment of bladder cancer.

SYNTHESIS, CHARACTERIZATION, IN SILICO OPTIMIZATION, AND CONFORMATIONAL STUDIES OF METHYL 4-O-PIVALOYL-α-L-RHAMNOPYRANOSIDES

Considering promising biological activities of natural and synthetic rhamnopyranoside esters, we have synthesized several methyl 4-O-pivaloyl-α-L-rhamnopyranosides via selective 2,3-O-acetonide protection of methyl α-L-rhamnopyranoside (4) followed by C-4 pivaloylation, and deprotection. The synthesized 4-O-pivaloate 7 and its 2,3-di-O-esters 8a-e are characterized by spectroscopy and are optimized by using density functional theory (DFT). The free energy and bond angles thus calculated are used to establish the probable conformation(s). The 2,3-O-acetonide protected rhamnopyranosides 5-6 are found to be slightly distorted from the regular 1C4 conformation, and exist between the chair and twist-boat (skew) conformation while other pivaloyl esters 7-8a-e exist in regular 1C4 chair conformation.

Authority, conformity and obedience: Applying Friedrich's theory of authority to the classics.

In the conformity and obedience studies of Asch and Milgram, legitimate authority is defined as a form of power to which subjects submit irrationally. This view assumes a causative process which the subjects' behaviour is said to manifest. Furthermore, this view assumes that there is illegitimate (or malevolent) authority. Carl J. Friedrich's theory of authority as reasoned elaboration offers an alternative perspective, which reveals conceptual differences between authority and such related constructs as power and legitimacy. When these concepts are properly distinguished, a re-interpretation of the classical studies of conformity and obedience is called forth. Such an exercise produces insights into some of the discipline's most controversial, if not disturbing, results. Specifically, it leads to an understanding of laboratory conformity and obedience in rational terms.

Schistosomicidal evaluation of synthesized bromo and nitro chalcone derivatives

Chalcones are compounds associated to several biological activities. The modification of chemical structures is one of the most widely used tool in the pharmaceutical industry to obtain new drugs. In this study, we synthetized chalcones with nitro and bromo substituents in different positions in the aromatic rings. NMR spectroscopy was used for characterization. Simultaneously, a conformational study of the compounds was carried out employing theoretical calculations. Furthermore, the schistosomicidal in vitro effect of bromo and nitro chalcone substituents on adult Schistosoma mansoni was investigated. The results showed that most chalcones have a conformational preference for s-cis geometry, which is favored by the conjugative effect of electronic delocalization. However, chalcones with ortho substituents dissipate greater stabilization of s-trans conformations, possibly for favoring surfaces with weak interactions such as Van der Waals. In addition, a significant effect of chalcones on female and male S. mansoni was observed. All samples evaluated reduced the motor activity of worms, caused mortality in male and female worms, and resulted in morphological alterations in a concentration- dependent manner (25–200 μg/mL) in a period of 6–24 h of incubation. Additionally, chalcones influenced the separation of couple worms and suppressed egg production at sublethal concentrations. Our results demonstrated that chalcones present potential to be used as schistosomicidal drugs, contributing to the clarification of the relation between the molecule conformation and the associated biological effects.

Conformity and Homogeneity Indices for Brain Cancer Patients Using 3DCRT Technique

Background: 3D conformal radiotherapy 3DCRT technique are used to treat patients with brain cancer. Goal: this study aims to compare conformity and homogeneity indices for eight patients of brain cancer by using three-dimension conformal radiotherapy (3DCRT) technique on planning target volume (PTV) located in brain. Methods: Comparative study of Conformity and Homogeneity indices for ten brain cancer patients during period from October 2019 to March 2020 that carried out at ZCC (Zhianawa Cancer Center) in Sulaimany-Iraq. 3DECRT technique was applied to get the heist dosage to the target volume (tumor) and lowest dose to the healthy structures around the tumor. By using Linear Accelerator machine- LINAC, Elekta synergy type with 6MV photon beam. SPSS-version 22 was applied for analyzing and caring out the data measurements. Results: It has been observed from the results, in both techniques the highest conformity and homogeneity indices have the acceptable values, in this study with 3D-CRT plan technique showed that the mean conformity and homogeneity indices were (0.1999 ± 0.03, 0.9457 ± 0.05) respectively. The mean dose values for organs at risk spinal cord and brain stem were (41.98 ± 2.23, 26.01 ± 16.62) respectively, for ten right and left parotid glands were (23.52 ± 3.99, 23.34 ± 3.93) respectively. In both plans, the average dose values for all organs at risk mentioned above were less than tolerance radiation doses. Conclusion: This study also supports that indices of homogeneity and conformity are important tools for improving the long-term quality of life of brain cancer patients using 3DCRT technology.

Super interactive promoters provide insight into cell type-specific regulatory networks in blood lineage cell types.

Existing studies of chromatin conformation have primarily focused on potential enhancers interacting with gene promoters. By contrast, the interactivity of promoters per se, while equally critical to understanding transcriptional control, has been largely unexplored, particularly in a cell type-specific manner for blood lineage cell types. In this study, we leverage promoter capture Hi-C data across a compendium of blood lineage cell types to identify and characterize cell type-specific super-interactive promoters (SIPs). Notably, promoter-interacting regions (PIRs) of SIPs are more likely to overlap with cell type-specific ATAC-seq peaks and GWAS variants for relevant blood cell traits than PIRs of non-SIPs. Moreover, PIRs of cell-type-specific SIPs show enriched heritability of relevant blood cell trait (s), and are more enriched with GWAS variants associated with blood cell traits compared to PIRs of non-SIPs. Further, SIP genes tend to express at a higher level in the corresponding cell type. Importantly, SIP subnetworks incorporating cell-type-specific SIPs and ATAC-seq peaks help interpret GWAS variants. Examples include GWAS variants associated with platelet count near the megakaryocyte SIP gene EPHB3 and variants associated lymphocyte count near the native CD4 T-Cell SIP gene ETS1. Interestingly, around 25.7% ~ 39.6% blood cell traits GWAS variants residing in SIP PIR regions disrupt transcription factor binding motifs. Importantly, our analysis shows the potential of using promoter-centric analyses of chromatin spatial organization data to identify biologically important genes and their regulatory regions.

Hubungan Antara Konformitas Teman Sebaya dengan Pengambilan Keputusan Studi Lanjut Siswa SMP

THE CORRELATION BETWEEN PEER CONFORMITY WITH FURTHER STUDY DECISION MAKING OF JUNIOR HIGH SCHOOL. This research was holded based on the phenomenon of Junior High School students who were less independent in further study decision making, so that they adapted based on peer conformity. The research aims to find out the relatonship between peer conformity with further study decision making in Junior High School students. This type of research is ex post facto quantitative with a correlational design. The samples of this research totaled 233 students from five schools with cluster sampling and proportional random sampling techniques. The instruments is used consisted of further study decision making scale, and peer conformity scale. Based on the result analysis, it showed that level further study decision making is high, level peer conformity is medium, and there is finded a negative and significant relationship between peer conformity and further study decision making (r=-0,364, p=0,000 < 0,05).

Feeling at Home in Two Cultural Worlds: Bicultural Identity Integration Moderates Felt Authenticity

Bicultural individuals navigate and identify with two cultures. Biculturals differ in levels of Bicultural Identity Integration (BII)—how much their two cultural identities are combined and compatible (high BII) versus divided and conflicting (low BII). We hypothesized that during conformity in cultural ingroup contexts, biculturals with low BII feel inauthentic (being untrue to themselves), whereas biculturals with high BII feel authentic (being true to themselves). Across four experiments with Asian-Americans, expressing cultural conformity (vs. non-conformity) in Asian or American contexts produced felt inauthenticity among participants with low BII but not high BII (Studies 1–3). Felt inauthenticity was due to cultural identity threat (perceived identity exclusion) (Study 2). Activating self-kindness counteracted felt inauthenticity for low BII participants during cultural conformity (Study 3) and produced felt authenticity (Study 4). Our findings imply that responding kindly to the self makes biculturals at ease in their cultural homes, at least temporarily.

Conformational Analysis and Through‐Chain Charge Propagation in Ferrocenyl‐Conjugated Homopeptides of 2,3‐Diaminopropionic acid (Dap)

AbstractThis work reports a detailed conformational and electrochemical study of two series of ferrocene (Fc)‐peptide conjugates, based on the side‐chain protected, 2,3‐diaminopropionic acid (L−Dap). In one series Fc is linked to the N‐terminus, in the other to the C‐terminus of the Dap homo‐peptides. The conformational analysis carried out in solution (IR absorption and NMR) and in the crystal state (X‐ray diffraction) suggests that these peptides adopt a 310‐helical structure. Cyclic voltammetry showed that the peptide length positively or negatively affects the oxidation potential of Fc. The two opposite trends are correlated to the different orientation of the macrodipole moment of the 310‐helix in the two series with respect to the position of the Fc group in the chain. Finally, the variation of the IR absorptions upon chemical oxidation indicates that our 310‐helical conjugates are very efficient in transferring the positive charge along the peptides through the H‐bond network.