Effect of Early pregnancy associated protein-1 on Spike protein and ACE2 interactions: Implications in SARS Cov-2 vertical transmission.

INTRODUCTION: Several factors influence transmission of 2019-nCoV from mother to fetus during pregnancy, thus the dynamics of vertical transmission is unclear. The role of cellular protective factors, namely a 90 KDa glycoprotein, Early pregnancy-associated protein (Epap-1), expressed by placental endothelial cells in women during early pregnancy would provide an insight into role of placental factors in virus transmission. Since viral spike protein binding to the ACE2 receptors of the host cells promotes virus invasion in placental tissue, an analysis of effects of Epap-1 on the Spike-ACE2 protein binding was studied. METHODS: Epap-1 was isolated from MTP placental tissue. Molecular interaction of Epap-1 and variants of the spike was analyzed in silco. The interaction of Epap-1 with Spike and RBD were analyzed using ELISA and immunofluorescence studies. RESULTS: The results in silico showed an interaction of Epap-1 with S-protein at RBD region involving K417, Y449, Y453, Y456, Y473, Q474, F486, Q498, N501 residues of spike with Y61, F287, I302, N303, N305, S334, N465, G467, N468 residues of Epap-1 leading to interference of S-protein and ACE2 interaction [1]. Further, the interaction is conserved among the variants. The studies in vitro confirm that Epap-1 affects S protein-ACE2 and RBD- ACE2 binding, thus suggesting that during early pregnancy, SARS CoV-2 infection may be protected by Epap-1 protein present in placental tissue. The results were further confirmed by pseudovirus expressing Spike and RBD in an infection assay. DISCUSSION: Epap-1 interferes with Spike and RBD interaction with ACE2, suggesting a possible mechanism of the antiviral environment during pregnancy.

Evaluation of stress and deformation in bone with titanium, CFR-PEEK and zirconia ceramic implants by finite element analysis.

Background: As more recent implant biomaterials, Zirconia ceramic and glass or carbon fibre reinforced PEEK composites have been introduced. In this study, bone stress and deformation caused by titanium, carbon fiber-reinforced polyetheretherketone (CFRPEEK), and zirconia ceramic implants were compared. Materials and Methods: In this in vitro finite element analysis study, a geometric model of mandibular molar replaced with implant supported crown was generated. The study used an implant that was 5 mm diameter and 11.5 length. Three implant assemblies made of CFR- polyetheretherketone (PEEK), zirconium, and titanium were created using finite element analysis (FEM). On the implant's long axis, 150 N loads were applied both vertically and obliquely. ANSYS Workbench 18.0 and finite element software were used to compare the Von Mises stresses and deformation produced with a significance level of P < 0.05. Results: With no discernible differences, all three implant assemblies that is CFR-PEEK, titanium, and zirconia demonstrated similar stresses and deformation in bone. Conclusion: It was determined that zirconia and PEEK and reinforced with carban fibres (CFR-PEEK) can be used as titanium-free implant biomaterial substitutes.

Spectroscopic Studies on the Interaction of Naphthyridines with DNA and Fluorescent Detection of DNA in Agarose Gel.

Four new naphthyridine derivatives (R1-R4) possessing amino acid or boronic acid moieties have been synthesized and characterized using 1H and 13C NMR, FT-IR, and mass spectral techniques. The mechanism of binding of these probes with calf thymus DNA (CT-DNA) has been delineated through UV-Vis, fluorescence, and circular dichroism (CD) spectral techniques along with thermodynamic and molecular docking studies. Small hypochromicity in absorption maximum of the probes without any shift in wavelength of absorption suggests groove binding mode of interaction of these probes with CT-DNA, confirmed by CD and 1H NMR spectral data competitive binding assay with ethidium bromide (EB). CT-DNA quenches the fluorescence of these probes via a static quenching mechanism. In the case of R1 and R4, the observed ΔHo < 0 and ΔSo > 0suggest that these probes interact with CT-DNA through H-bonding and hydrophobic interactions, while in the interaction of R2 and R3, van der Walls and H-boding forces are found to be dominant (ΔHo < 0 and ΔSo < 0). Results of molecular docking investigations corroborate well with that of spectral studies, and these probes bind in the minor groove of DNA. These probes are found to be effective fluorescent staining agents for DNA in agarose gel in gel electrophoresis experiment with sensitivity comparable to that of EB, and DNA amounts as low as 37.5 ng are visually detectable in the gel.

Multi-site probe for selective turn-on fluorescent detection of Al(III) in aqueous solution: synthesis, cation binding, mode of coordination, logic gate and cell imaging.

An easy to make organic probe (hereafter called as R) possessing multiple ligating sites have been synthesized and characterized using spectral techniques. The probe exhibits selective and sensitive turn-on fluorescence response with Al(III) in aqueous dimethylformamide (DMF) (1:1 v/v) solution. Fluorescence titration experiment shows that the probe binds with Al(III) with a 1:1 stoichiometry and a binding constant of 6.6 × 104 M-1.The mode of coordination of R with Al(III) has been established suing 27Al and 1H NMR studies and the results suggest formation of an octahedral complex been them. The suggested point of attachment of R with Al(III) corroborates well with Density Functional Theory (DFT) optimized structure and Mulliken charges computed. Chelation-enhanced fluorescence (CHEF) is proposed as the mechanism of enhancement of fluorescence upon addition of Al(III) to R. The probe detects Al(III) in aqueous solution with a detection limit of 0.2 µM, which is much lower than the permissible limit of Al(III) set by the World Health Organization (WHO).The probe works in a wide pH range (4-11) and thus makes it a suitable candidate for environmental and biological applications. The fluorescence signals of R were used to construct an INHIBIT molecular logic gate. The confocal fluorescence microscope experiments show that R could be employed as a fluorescent probe for detecting Al(III) in living cells.

Multi-spectroscopic, voltammetric and molecular docking studies on binding of anti-diabetic drug rosigiltazone with DNA.

The binding of an anti-diabetic drug rosiglitazone (RG) with calf-thymus DNA (CT-DNA) in physiological buffer (pH 7.4) has been investigated using various spectral techniques such as UV-Vis, fluorescence, 1H NMR and circular dichroism (CD) coupled with viscosity measurement and molecular docking studies. The binding of RG with CT-DNA results in small hypochromism without any change in absorption maximum and fluorescence quenching with hardly any shifts in emission maximum suggesting groove binding mode of interaction. The binding constant is found to be 4.2 × 102 M-1 at 298 K. Thermodynamic analysis reveal that the binding is spontaneous and H-bonding and van der Waals forces play predominant role in the binding of RG with CT-DNA. Competitive interaction between RG and ethidium bromide with CT-DNA, viscosity measurements, KI quenching, 1H NMR and CD studies substantiate the prosed mode of binding. Voltammetric investigations suggest that the electro-reduction of RG is an adsorption controlled process and shift of reduction peak to more negative potential, with a binding constant of 3.4 × 103 M-1, validates the groove binding mode of interaction between RG and CT-DNA. Molecular docking reveals that RG binds in the minor groove of DNA and the dominating interaction forces are H-bonding and hydrophobic interactions.

Spectroscopic investigations on DNA binding profile of two new naphthyridine carboxamides and their application as turn-on fluorescent DNA staining probes.

Two new 10-methoxydibenzo[b,h][1,6]naphthyridine-2-carboxamide derivatives (R1 and R2) have been synthesized and characterized using different spectral techniques. The binding of these probes with DNA was investigated using spectral (Electronic, fluorescence, 1H NMR and circular dichroism) and molecular docking studies. These probes exhibited a strong fluorescence around 440 nm upon excitation around 380 nm. Electronic and competitive fluorescence titration studies, in HEPES [(4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid)] buffer/dimethyl sulfoxide (pH 7.4) medium, suggest that these probes bind strongly to DNA, which is substantiated by 1H NMR study. The binding constants are calculated to be 5.3 × 107 and 6.8 × 106 M-1 for R1 and R2, respectively. From the results of spectral studies, it is proposed that the mechanism of binding of these probes with DNA is through minor groove binding mode, which is further confirmed by circular dichroism and molecular docking studies. Initial cell viability screening using MTT (3-[4,5-methylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay shows that normal Vero cells are viable towards these probes at nano molar concentration, which is the concentration range employed in the present study for DNA staining (IC50 in the order of 0.023 mM). The enhancement in fluorescence intensity of these probes upon binding with DNA enables the staining of DNA in agarose gel in gel electrophoresis experiment. The sensitivity of these probes is comparable with that of ethidium bromide and DNA amounts as low as 4 nano gram are detectable.Communicated by Ramaswamy H. Sarma.

Oligoamnios and Perinatal Outcome.

OBJECTIVES: We aimed at evaluating the predictive value of amniotic fluid index ≤5 on perinatal outcome in terms of effect on cardiotocography, mode of delivery, meconium in liquor, birth weight, fetal distress, APGAR score at birth and neonatal admission to ICU. METHODS: This is a prospective study of 308 antenatal women admitted to labor ward of MIMS during February 2014-December 2015 with gestational ages between 34 and 41 weeks. All women enrolled were subjected to history taking, examination, AFI estimation and compared between those with AFI ≤5 from rest. RESULTS: The non-reactive CTG, cesarean section rate due to fetal distress, low birth weight, APGAR score <7 and NICU admission were significantly high among those with oligoamnios than the control group. CONCLUSION: Oligoamnios has a significant correlation with adverse perinatal outcome.

NBO, HOMO, LUMO analysis and vibrational spectra (FTIR and FT Raman) of 1-Amino 4-methylpiperazine using ab initio HF and DFT methods.

Experimental FTIR and FT-Raman spectroscopic analysis of 1-Amino-4-methylpiperazine (1A4MP) have been performed. A detailed quantum chemical calculations have been carried out using ab initio HF and density functional theory calculations (B3LYP) with 6-311+G(d,p) basis set. The atomic charges, electronic exchange interaction and charge delocalization of the molecule have been performed by natural bond orbital (NBO) analysis. Electron density distribution and frontier molecular orbitals (FMOs) have been constructed at B3LYP/6-311+G(d,p) level to understand the electronic properties. The charge density distribution and site of chemical reactivity of the molecule have been obtained by mapping electron density isosurface with electrostatic potential surfaces (ESP). The electronic properties, HOMO and LUMO energies were measured by time-dependent TD-DFT approach. The dipole moment (µ), polarizability (α), anisotropy polarizability (Δα) and hyperpolarizability (ß) of the molecule have been reported.

Molecular structure, vibrational spectra (FTIR and FT Raman) and natural bond orbital analysis of 4-Aminomethylpiperidine: DFT study.

The FT-IR and FT-Raman spectra of 4-Aminomethylpiperidine have been recorded using Perkin Elmer Spectrophotometer and Nexus 670 spectrophotometer. The equilibrium geometrical parameters, various bonding features, the vibrational wavenumbers, the infrared intensities and the Raman scattering activities were calculated using Hartree-Fock and density functional method (B3LYP) with 6-311+G(d,p) basis set. Detailed interpretations of the vibrational spectra have been carried out with the aid of the normal coordinate analysis. The spectroscopic and natural bonds orbital (NBO) analysis confirms the occurrence of intra molecular hydrogen bonds, electron delocalization and steric effects. The changes in electron density in the global minimum and in the energy of hyperconjugative interactions of 4-Aminomethylpiperidine (4AMP) were calculated. The theoretical UV-Visible spectrum of the compound was computed in the region 200-400nm by time-dependent TD-DFT approach. The calculated HOMO and LUMO energies show that charge transfer occur within the molecule. The dipole moment (µ) and polarizability (α), anisotropy polarizability (Δα) and hyperpolarizability (ß) of the molecule have been reported.

FT-IR and FT-Raman spectra, normal coordinate analysis and ab initio computations of Trimesic acid.

The FT-IR and FT-Raman spectra have been recorded of Trimesic acid (1,3,5-benzenetricarboxylic acid, H3BTC). The molecular structure, conformational stability, geometry optimization, vibrational frequencies have been investigated. The total energy calculations of H3BTC were tried for various possible conformers. The spectra were interpreted with the aid of normal coordinate analysis based on ab initio Hartree-Fock (HF) and density functional theory (DFT/B3LYP) methods and 6-31+G(d,p) basis set level and was scaled using scale factors yielding good agreement between observed and calculated frequencies. Vibrational assignments and Natural bonding orbital (NBO) calculations are performed on the stable monomer of H3BTC using the same level of theory. Intramolecular hydrogen bond exists via COOH group gives the evidence for the formation of dimer entities in the title molecule. UV-VIS spectral analyses of H3BTC have been researched by theoretical calculations. In order to understand electronic transitions of the compound, TD-DFT calculations on electronic absorption spectra in gas phase and solvent (DMSO and Chloroform) were performed. The calculated frontier orbital energies, absorption wavelengths (λ), oscillator strengths (ƒ) and excitation energies (E) for gas phase and solvent (DMSO and Chloroform) are also illustrated. The statistical thermodynamic functions were obtained for the range of temperature 100-1000 K. Reliable vibrational modes associated with H3BTC are made on the basis of total energy distribution (TED) results obtained from scaled quantum mechanical (SQM) method.

FT-IR, FT-Raman and DFT study of 3,3'-bis (trifluoromethyl) benzophenone and its biological activity with other halogen (Cl, Br) atoms.

The FT-IR and FT-Raman spectra of 3,3'-bis (trifluoromethyl) benzophenone (TFMBP) were recorded and analyzed. Natural bond orbital analysis on TFMBP, 3,3'-bis (trichloromethyl) benzophenone (TCMBP) and 3,3'-bis (tribromomethyl) benzophenone (TBMBP) has been carried out for various intramolecular interactions that are responsible for the stabilization of the molecule. HOMO-LUMO energy gap of the halogen substitution (Cl, Br) has been computed with the help of density functional theory. The statistical thermodynamic functions (heat capacity, entropy, vibrational partition function and Gibbs energy) were obtained for the range of temperature 100-1000 K. The polarizability, first hyperpolarizability, anisotropy polarizability invariant has been computed using quantum chemical calculations. The infrared and Raman spectra were also predicted from the calculated intensities. Comparison of the experimental and theoretical spectra values provides important information about the ability of the computational method to describe the vibrational modes. UV-VIS spectral analyses of TFMBP have been researched by theoretical calculations. In order to understand electronic transitions of the compound, TD-DFT calculations on electronic absorption spectra in gas phase and solvent (DMSO and Chloroform) were performed. The calculated frontier orbital energies, absorption wavelengths (λ), oscillator strengths (ƒ) and excitation energies (E) for gas phase and solvent (water and methanol) are also illustrated.

DFT, FT-Raman, FT-IR, HOMO-LUMO and NBO studies of 4-Methylmorpholine.

The experimental FT-IR (4000-400 cm(-1)) and FT-Raman (3500-100 cm(-1)) spectra of 4-Methylmorpholine were recorded. The observed bands were interpreted with the aid of normal coordinate analysis and force field calculations based on density functional theory (DFT) using B3LYP functional theory (DFT) using B3LYP functional with 6-311+G and 6-3++G basis sets. The complete assignments were performed on the basis of the potential energy distribution (PED) of the vibrational modes, calculated with scaled quantum mechanical (SQM) method. The molecular structure and vibrational frequencies, infrared intensities and Raman scattering actives have been calculated frequency showed the best agreement with experimental results. The formation of the hydrogen bond was investigated using NBO calculations. The calculated HOMO and LUMO energies show that charge transfer occur within the molecule. The dipolemoment (µ) and polarizability (α), anisotropy polarizability (Δα) and first hyperpolarizability (ß(total)) of the molecule have been reported.