In vitro antioxidant activities of the methanol extract and its different solvent fractions obtained from the fruit pericarp of Terminalia bellerica

Terminalia bellerica has been used as a traditional medicine in a variety of ailments including anaemia, asthma, cancer, inflammation, rheumatism and hypertension. In this study, the free radical scavenging and antioxidant activities of methanol extract (ME) and its different solvent fractions (namely hexane (HE), ethyl acetate (EA), butanol (BL) and water (WA)) of the T. bellerica fruit pericarp were evaluated and compared with standard antioxidant compounds like gallic acid (GA), catechin and ascorbic acid. Among the different fractions tested, the EA fraction exhibited higher antioxidant and radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide and hydroxyl radicals than the other fractions, which may be attributed to its higher phenolic and flavonoid content, since a linear relation was observed between the phenolic content and the antioxidant parameters. The HPTLC analysis of the EA fraction revealed that it mainly contains GA and ferulic acid (FA) as major phenolics, and the higher antioxidant activities of EA fraction may be due to the presence of these compounds.     

In vitro antiperoxidative, free radical scavenging and xanthine oxidase inhibitory potentials of ethyl acetate fraction of Saraca ashoka flowers

Saraca ashoka is a widely used medicinal herb claimed to cure many diseases. This study investigated the antiperoxidative, free radical scavenging and xanthine oxidase (XO) inhibitory potential of the ethyl acetate fraction of S. ashoka flowers (SAF) and compared it with standard compounds like gallic acid, ascorbic acid, butylated hydroxyl toluene and allopurinol. The ethyl acetate fraction of SAF exhibited free radical scavenging activity against the 1,1-diphenyl-2-picrylhydrazyl radical and superoxide radical, along with hydroxyl radical scavenging activity. Lipid peroxidation inhibitory potential of SAF was studied using a linoleic acid emulsion system, which shows significant antioxidant potential. SAF also demonstrated significant XO (key enzyme linked to inflammation) inhibitory activity, which revealed its therapeutic potential as an antioxidant and XO inhibitor. HPLC profiling of the ethyl acetate fraction of SAF revealed that it contains ellagic acid as a major compound and thus the beneficial effects of this fraction may be due to the presence of this compound.     

A labeling scheme for young tableaux spanning representations of permutation group S(N)

A structure‐dependent labeling scheme for the Standard Young Tableaux spanning the representations of the permutation group is outlined in the present work. This scheme is used to generate the representations of a select class of permutations such as dense cycles and general transpositions of the group using minimal storage requirements. Two distinct approaches are outlined for generating the tableaux in the present labeling scheme. Detailed application has been made to two‐column Young diagram representations that are extremely useful in electron correlation studies in molecules. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 185–190, 2000     

Evaluation of the Probiotic Characteristics of Newly Isolated Lactic Acid Bacteria

Lactic acid bacteria were isolated from fermented vegetables, sour dough, milk products, sheep and human excreta. The newly isolated cultures were evaluated for a number of probiotic characteristics like bile salt resistance, salt tolerance in general, survival in low pH, hydrophobicity of the cell surface, resistance to low phenol concentration, antimicrobial activity and susceptibility pattern against vancomycin and erythromycin. The selected cultures were further screened for their ability to produce the nutraceticals such as folic acid and exopolysaccharide (EPS). Two potent isolates, CB2 (from cabbage) and SD2 (from sour dough) were found to produce both extracellular and intracellular folate. One of the isolates from yogurt (MC-1) and the one from whey (W3) produced significant amount of EPS with a maximum production of 8.79 +/- 0.05 g/l by MC-1.     

In silico screening of neurokinin receptor antagonists as a therapeutic strategy for neuroinflammation in Alzheimer’s disease

Neuroinflammation is one of the detrimental factors leading to neurodegeneration in Alzheimer’s disease (AD) and other neurodegenerative disorders. The activation of microglial neurokinin 1 receptor (NK1R) by substance P (SP) enhances neuroinflammation which is mediated through pro-inflammatory pathways involving NFkB, ERK1/2, and P38 and thus projects the scope and importance of NK1R inhibitors. Emphasizing the inhibitory role of N Acetyl l Tryptophan (l-NAT) on NK1R, this is the first in silico screening of l-NAT mediated NK1R antagonism. In addition, FDA- approved ligands were screened for their potential NK1R antagonism. The l-NAT was docked in XP (Extra Precision) mode while FDA-approved ligands were screened in HTVS (High Throughput Virtual Screening), SP (Standard Precision), and XP mode onto NK1R (PDB:6HLO). The l-NAT and top 3 compounds FDA-approved ligands were subjected to molecular dynamics (MD) studies of 100 ns simulation time. The XP docking of l-NAT, indacaterol, modafinil and alosetron showed good docking scores. Their 100 ns MD showed brief protein–ligand interactions with an acceptable root mean square deviation. The protein–ligand contacts depicted pi-pi stacking, pi-cation, hydrogen bonds, and water bridges with the amino acids necessary for NK1R inhibition. The variable colour band intensities on the protein–ligand contact map indicated their binding strength with amino acids. The molecular mechanics/generalized born surface area (MM-GBSA) scores suggested favourable binding free energy of the complexes. Thus, our study predicted the ability of l-NAT, indacaterol, modafinil, and alosetron as capable NK1R inhibitors that can aid to curb neuroinflammation in conditions of AD which could be further ascertained in subsequent studies.

Graphic Abstract

     

Engineering bio-mimicking functional vesicles with multiple compartments for quantifying molecular transport

Controlled design of giant unilamellar vesicles under defined conditions has vast applications in the field of membrane and synthetic biology. Here, we bio-engineer bacterial-membrane mimicking models of controlled size under defined salt conditions over a range of pH. A complex bacterial lipid extract is used for construction of physiologically relevant Gram-negative membrane mimicking vesicles whereas a ternary mixture of charged lipids (DOPG, cardiolipin and lysyl-PG) is used for building Gram-positive bacterial-membrane vesicles. Furthermore, we construct stable multi-compartment biomimicking vesicles using the gel-assisted swelling method. Importantly, we validate the bio-application of the bacterial vesicle models by quantifying diffusion of chemically synthetic amphoteric antibiotics. The transport rate is pH-responsive and depends on the lipid composition, based on which a permeation model is proposed. The permeability properties of antimicrobial peptides reveal pH dependent pore-forming activity in the model vesicles. Finally, we demonstrate the functionality of the vesicles by quantifying the uptake of membrane-impermeable molecules facilitated by embedded pore-forming proteins. We suggest that the bacterial vesicle models developed here can be used to understand fundamental biological processes like the peptide assembly mechanism or bacterial cell division and will have a multitude of applications in the bottom-up assembly of a protocell.

Giant vesicle functional models mimicking a bacterial membrane under physiological conditions are constructed.     

Bioactives of Microbes Isolated from Western Ghat Belt of Kerala Show β-Lactamase Inhibition along with Wide Spectrum Antimicrobial Activity

The present study describes the exploitation of microbial biodiversity from Western Ghats of Kerala for screening of bioactives having β-lactamase inhibitory activities. A total of 700 pure cultures were isolated and were screened for antibacterial activity against a β-lactam resistant Bacillus cereus strain (PL 10) isolated from the same niche. Bioactive extracts made from 45 isolates showed inhibitory activities against PL 10, of which two strains showed inhibition of extended spectrum β-lactamase (ESBL) producing Klebsiella ESBL1101 and three strains inhibited methicillin-resistant Staphylococcus aureus (MRSA) strain MRSA831. All these five strains showed wide spectrum antimicrobial activity against various fungi and bacteria. These five cultures were identified by 16S rRNA sequencing and biochemical tests and the preliminary characterizations of their bioactive extracts were carried out. This study suggests the potential of bioactives from two inhibitor–producer strains, NII 167 and NII 1054, for being developed as inhibitors against wide spectrum β-lactam resistant strains.     

Synthesis,Colloidal Properties and Cytotoxicity of Biopolymer Nanoparticles

To characterize the physicochemical and biological stability of nanodevices suitable for biomedical applications, polylactic acid (PLA) nanoparticles (NPs) of 112?±?6 nm and polyhydroxy butyrate (PHB) of 15?±?5 nm size were prepared by standardizing the suitable method for each. Morphology of NPs was studied by scanning and transmission electron microscopy and temperature stability by thermogravimetric analysis. Their stability in biological fluids (simulated gastrointestinal and saliva) and tolerance against 0.5 mM NaCl were analyzed. PHB NPs remained stable in all fluids, while after 24 h treatment, the PLA NPs showed the beginning of disintegration with intestinal fluid mimic. In addition to the preparation of polyethylene glycol (PEG) surface-coated NPs, PLA–PEG–PLA triblock copolymer (MW?～?7,366 Da) was also chemically synthesized and characterized. Cytotoxicity of all forms of nanoparticles was tested by MTT assay and by annexin pi staining.     

Influence of disorder on superconductivity in non-magnetic rare-earth nickel borocarbides

The effect of substitutional disorder on the superconducting properties of YNi₂B₂C was studied by partially replacing yttrium and nickel by Lu and Pt, respectively. For the two series of (Y, Lu)Ni₂B₂C and Y(Ni, Pt)₂B₂C compounds, the upper critical field H _c2(T) and the specific heat c _p(T, H) in the superconducting mixed state have been investigated. Disorder is found to reduce several relevant quantities such as T _c, the upper critical field H _c2(0) at T=0 and a characteristic positive curvature of H _c2(T) observed for these compounds near T _c. The H _c2(T) data point to the clean limit for (Y, Lu) substitutions and to a transition to the quasi-dirty limit for (Ni, Pt) substitutions. The electronic specific heat contribution γ(H) exhibits significant deviations from the usual linear γ(H) law. These deviations reduce with growing substitutional disorder but remain even in the quasidirty limit which is reached in the Y(Ni_1−x , Pt _x )₂B₂C samples for x=0.1.     

Proline-Specific Extracellular Aminopeptidase Purified from <Emphasis Type="Italic">Streptomyces lavendulae</Emphasis>

Aminopeptidases catalyze the cleavage of specific amino acids from the amino terminus of protein or peptide substrates. A proline-specific aminopeptidase was purified to homogeneity from the culture-free extract of Streptomyces lavendulae ATCC 14162 in sequential steps comprising ammonium sulfate precipitation, ultra-filtration, and column chromatography on Q-sepharose and Sephadex G-100. The purified protein showed approximately 60 kDa in SDS-PAGE and was optimally active at pH 6.5 and 40 °C. Kinetic studies showed a K _m and V _max of 0.23 mM and 0.087 μmol/min, respectively, using Pro-p-NA, the substrate with maximum specificity. Enzyme activity was inhibited by PMSF and ions like Zn²⁺, Co²⁺, and Ni²⁺. However, unlike other aminopeptidases, the activity was enhanced in the presence of DTT, 1,10-phenanthroline, EDTA, amastatin, and bestatin. Ions like Ca²⁺, Mg²⁺, and Mn²⁺ also enhanced the activity.