Multisite and multivalent binding between cyanovirin-N and branched oligomannosides: calorimetric and NMR characterization

Binding of the protein cyanovirin-N to oligomannose-8 and oligomannose-9 of gp120 is crucially involved in its potent virucidal activity against the human immunodeficiency virus (HIV). The interaction between cyanovirin-N and these oligosaccharides has not been thoroughly characterized due to aggregation of the oligosaccharide-protein complexes. Here, cyanovirin-N's interaction with a nonamannoside, a structural analog of oligomannose-9, has been studied by nuclear magnetic resonance and isothermal titration calorimetry. The nonamannoside interacts with cyanovirin-N in a multivalent fashion, resulting in tight complexes with an average 1:1 stoichiometry. Like the nonamannoside, an alpha1-->2-linked trimannoside substructure interacts with cyanovirin-N at two distinct protein subsites. The chitobiose and internal core trimannoside substructures of oligomannose-9 are not recognized by cyanovirin-N, and binding of the core hexamannoside occurs at only one of the sites on the protein. This is the first detailed analysis of a biologically relevant interaction between cyanovirin-N and high-mannose oligosaccharides of HIV-1 gp120.     

Biodegradation of Fluoranthene by Basidiomycetes Fungal Isolate <Emphasis Type="Italic">Pleurotus Ostreatus</Emphasis> HP-1

The biodegradation of fluoranthene, a high molecular weight polycyclic aromatic hydrocarbon (PAH), was investigated in submerged culture using the wood decaying fungus isolated from forest locality in Gujarat, India. The basidiomycete fungal isolate was found to have an ability to grow on sabaroud dextrose agar containing 50 mgl⁻¹ of each naphthalene, anthracene, acenaphthene, benzo (a) anthracene, pyrene, flouranthene, carbazole, and biphenyl. The involvement of extracellular fungal peroxidases such as manganese peroxidase (MnP) and laccase (Phenol oxidase) in the degradation of fluoranthene was studied. On the eighth day of incubation 54.09% of 70 mg l⁻¹ fluoranthene was removed. There after no PAHs removal was observed till the 20th day of the incubation period. The isolate was identified as Pleurotus ostreatus by 18S rRNA, 5.8S rRNA, and partial 28S rRNA gene sequencing. To the best of our knowledge this is the first time Pleurotus ostreatus have been reported to degrade such a high concentration of fluoranthene within much lower time period of incubation. Depletion in the residual fluoranthene in the culture medium was determined by HPLC. Attempts were made to identify the degradation product in the culture medium with the help of FT-IR, NMR, and HPTLC analysis. In the present study positive correlation between fluoranthene degradation and the ligninolytic enzyme (MnP and laccase) production is observed, thus this isolate can play an effective role for bioremediation of PAHs contaminated sites.     

Structural phase stability,mechanical and anharmonic properties of actinide sulfides: a high pressure study with the role of temperature

Vital properties (structural and thermo-elastic) of materials are affected on the application of pressure and temperature. These properties play a key role in understanding the thermodynamic behavior and equation of state. Thus, we have formulated a realistic interaction potential model to study the structural and thermo-elastic of US and ThS including the temperature effects. This model is used for the present compounds in a high-pressure study including temperature effects. We have computed phase transition pressures, volume drop, elastic and thermal properties at different pressures, and elevated temperatures. Our results are in agreement with available experimental and theoretical data.     

Mentha arvensis essential oil suppressed airway changes induced by histamine and ovalbumin in experimental animals

The present investigation aimed to evaluate the activity of the essential oil of Mentha arvensis L. on exogenously induced bronchoconstriction in experimental animals. The anti-asthmatic effect of M. arvensis essential oil (MAEO) was studied using histamine aerosol-induced bronchoconstriction in guinea pigs and ovalbumin (OVA) sensitised albino mice. Treatment with M. arvensis oil significantly (p < 0.001) increased the time of preconvulsive dyspnoea in histamine-induced guinea pigs. Oral treatment of MAEO significantly (p < 0.001) decreased absolute eosinophil count, serum level of IgE and the number of eosinophils, neutrophils in BALF. Histopathological examination of lungs showed that essential oil rescinded bronchial asthma. The present investigation provides evidence that MAEO relaxes bronchial smooth muscles and suppressed immunological response to OVA.     

Six-coordinated oxovanadium(V) complexes of reduced Schiff bases derived from amino acids: synthesis,reactivity and redox studies

New oxovanadium(V) complexes, [VOL(hq)] (1)–(4) have been prepared by the reaction of [VO(acac)₂] with ligands LH₂ in the presence of 8-hydroxyquinoline (Hhq). LH₂ is the dibasic tridentate ONO Mannich base [(S)-H₂glysal, (S)-H₂alasal, (S)-H₂leusal and (S)-H₂ileusal; S represents the S-enantiomer] obtained by the reduction of the Schiff bases of salicylaldehyde (sal) and the amino acids: glycine (gly), DL-alanine (ala), leucine (leu) and isoleucine (ileu), respectively. Spectral studies suggest an octahedral structure for these complexes. The complexes exhibit a single ⁵¹V-n.m.r. signal at –464.6 to –468.0 p.p.m. due to the existence of a single isomeric species in solution. In the presence of L-ascorbic acid under aerobic conditions [VO(S-glysal)(hq)] (1) and [VO(S-isoleusal)(hq)] (4) are converted into the corresponding dioxo species possible via intermediate reduction. A time- dependent ⁵¹V-n.m.r. study has also been carried out in order to investigate the possible isomerisation and/or further reaction in solution.     

Palladium-catalyzed one-step synthesis of isoindole-1,3-diones by carbonylative cyclization of o-halobenzoates and primary amines

The palladium-catalyzed aminocarbonylation of o-halobenzoates produces 2-substituted isoindole-1,3-diones in good yields. This methodology provides a good one-step approach to this important class of heterocycles and tolerates a variety of functional groups, including methoxy, alcohol, ketone, and nitro groups.     

Interaction of cobalt(III) polypyridyl complexes containing asymmetric ligands with DNA

Four asymmetric cobalt(III) complexes, [Co(bpy)₂(aip)]³⁺, [Co(bpy)₂(pyip)]³⁺, [Co(phen)₂(aip)]³⁺, and [Co(phen)₂(pyip)]³⁺ (bpy = 2,2,bipyridine, phen = 1,10-phenathroline), (pyip = 2-(1-pyrenyl)-1H-imidazo[4,5-f][phen], (aip = 2-(9-anthryl)-1H-imidazo[4,5,-f][phen], have been synthesized and characterized. Their interaction with calf thymus DNA (CT-DNA) was investigated by physico-chemical methods and photocleavage. The size and shape of the ligands have a marked effect on the DNA-binding affinity of the complexes. Irradiation of pBR322 DNA with these novel cobalt(III) complexes results in nicking of the plasmid DNA. Toxicity and induced cell death investigations revealed that the complexes of pyip had higher toxicity than those of aip. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Anticancer activity of Ophiobolin A,isolated from the endophytic fungus Bipolaris setariae

The present work describes the anticancer activity of Ophiobolin A isolated from the endophytic fungus Bipolaris setariae. Ophiobolin A was isolated using preparative HPLC and its structure was confirmed by HRMS, ¹H NMR, ¹³C NMR, COSY, DEPT, HSQC and HMBC. It inhibited solid and haematological cancer cell proliferation with IC₅₀ of 0.4–4.3 μM. In comparison, IC₅₀ against normal cells was 20.9 μM. It was found to inhibit the phosphorylation of S6 (IC₅₀ = 1.9 ± 0.2 μM), ERK (IC₅₀ = 0.28 ± 0.02 μM) and RB (IC₅₀ = 1.42 ± 0.1 μM), the effector proteins of PI3K/mTOR, Ras/Raf/ERK and CDK/RB pathways, respectively. It induced apoptosis and inhibited cell cycle progression in MDA-MB-231 cancer cells with concomitant inhibition of signalling proteins. Thus, this study reveals that anticancer activity of Ophiobolin A is associated with simultaneous inhibition of multiple oncogenic signalling pathways namely PI3K/mTOR, Ras/Raf/ERK and CDK/RB.     

Polymer-surfactant layered heterostructures by electropolymerization of phenosafranine in Langmuir-Blodgett films

Langmuir-Blodgett (LB) films of the water-soluble dye phenosafranine (PS) have been prepared by its adsorption from aqueous dye solution to an arachidic acid (AA) monolayer at the air-water interface. Atomic force microscopy (AFM) images of the LB films revealed the effect of change in pH of deposition on the degree of complexation of AA with the PS dye. Well-defined circular islands and holes were observed which disappeared with the increase in pH. Polarized absorption studies indicated that the dye molecules are oriented uniaxially with their long axis titled at a constant angle to the surface normal of the LB film. Within the restricted geometry of the LB film, the PS dye was electropolymerized to form a two-dimensional film of poly(phenosafranine) sandwiched between arachidic acid layers. The film was characterized by IR spectroscopy, cyclic voltammetry, and AFM. X-ray diffraction studies reveal the presence of a layer structure in the AA-PS LB film before and after polymerization. The polymer film showed highly anisotropic electrical conductivity of ca. 10 orders of magnitude. This indicates the formation of two-dimensional polyPS layers between arachidic acid layers resulting in a layered heterostructure film having alternate conducting and insulating regions. Also, the conductivity of the polyPS prepared from LB film was found to be approximately 2.5 times higher than the conductivity of polyPS prepared by solution polymerization method.     

Valve leaflet‐inspired elastomeric scaffolds with tunable and anisotropic mechanical properties

Fibrous scaffolds, which can mimic the elastic and anisotropic mechanical properties of native tissues, hold great promise in recapitulating the native tissue microenvironment. We previously fabricated electrospun fibrous scaffolds made of hybrid synthetic elastomers (poly(1,3‐diamino‐2‐hydroxypropane‐co‐glycerol sebacate)‐co‐poly (ethylene glycol) (APS‐co‐PEG) and polycaprolactone (PCL)) to obtain uniaxial mechanical properties similar to those of human aortic valve leaflets. However, conventional electrospinning process often yields scaffolds with random alignment, which fails to recreate the anisotropic nature of most of the soft tissues such as native heart valves. Inspired by the structure of native valve leaflet, we designed a novel valve leaflet‐inspired ring‐shaped collector to modulate the electrospun fiber alignment and studied the effect of polymer formulation (PEG amount [mole %] in APS‐co‐PEG; ratio between APS‐co‐PEG and PCL; and total polymer concentration) in tuning the biaxial mechanical properties of the fibrous scaffolds. The fibrous scaffolds collected on the ring‐shaped collector displayed anisotropic biaxial mechanical properties, suggesting that their biaxial mechanical properties are closely associated with the fiber alignment in the scaffold. Additionally, the scaffold stiffness was easily tuned by changing the composition and concentration of the polymer blend. Human valvular interstitial cells (hVICs) cultured on these anisotropic scaffolds displayed aligned morphology as instructed by the fiber alignment. Overall, we generated a library of biologically relevant fibrous scaffolds with tunable mechanical properties, which will guide the cellular alignment.