Propyl-2-(8-(3,4-Difluorobenzyl)-2 `,5 `-Dioxo-8-AzaspiroBicyclo3.2.1] Octane-3,4 `-Imidazolidine]-1 `-yl) Acetate Induces Apoptosis in Human Leukemia Cells through Mitochondrial Pathway following Cell Cycle Arrest

Background: Due to the functional defects in apoptosis signaling molecules or deficient activation of apoptosis pathways, leukemia has become an aggressive disease with poor prognosis. Although the majority of leukemia patients initially respond to chemotherapy, relapse is still the leading cause of death. Hence targeting apoptosis pathway would be a promising strategy for the improved treatment of leukemia. Hydantoin derivatives possess a wide range of important biological and pharmacological properties including anticancer properties. Here we investigated the antileukemic activity and mechanism of action of one of the potent azaspiro hydantoin derivative, (ASHD). Materials and Methods: To investigate the antileukemic efficacy of ASHD, we have used MTT assay, cell cycle analysis by FACS, tritiated thymidine incorporation assay, Annexin V staining, JC1 staining and western blot analysis. Results: Results showed that ASHD was approximately 3-fold more potent than the parent compounds in inducing cytotoxicity. Tritiated thymidine assay in conjunction with cell cycle analysis suggests that ASHD inhibited the growth of leukemic cells. The limited effect of ASHD on cell viability of normal cells indicated that it may be specifically directed to cancer cells. Translocation of phosphatidyl serine, activation of caspase 3, caspase 9, PARP, alteration in the ratio of BCL2/BAD protein expression as well as the loss of mitochondrial membrane potential suggests activation of the intrinsic pathway of apoptosis. Conclusion: These results could facilitate the future development of novel hydantoin derivatives as chemotherapeutic agents for leukemia.

Role of silica nanoparticles in conductivity enhancement of nanocomposite solid polymer electrolytes: (PEG(x) NaBr): ySiO(2)

Nanocomposite solid polymer electrolytes (NCSPEs) with conducting species other than Li ions are being investigated for solid-state battery applications. Pristine solid polymer electrolytes (SPEs) do not show ionic conductivity suitable for batteries. Addition of inert fillers to SPEs is known to enhance the ionic conductivity. In this paper, we present the role of silica nanoparticles in enhancing the ionic conductivity in NCSPEs with sodium as conducting species. Sodium bromide is complexed with the host polyethylene glycol polymer by solution cast method and silica nanoparticles (SiO2, average particle size 7 nm) are incorporated into the complex in small amounts. The composites are characterized by powder XRD and IR spectroscopy. Conductivity measurements are undertaken as a function of concentration of salt and also as a function of temperature using impedance spectroscopy. Addition of silica nanoparticles shows an enhancement in conductivity by 1-2 orders of magnitude. The results are discussed in terms of interaction of nanoparticles with the nonconducting anions.

Mechanistic features of Salmonella typhimurium propionate kinase (TdcD): Insights from kinetic and crystallographic studies

Short-chain fatty acids (SCFAs) play a major role in carbon cycle and can be utilized as a source of carbon and energy by bacteria. Salmonella typhimurium propionate kinase (StTdcD) catalyzes reversible transfer of the gamma-phosphate of ATP to propionate during L-threonine degradation to propionate. Kinetic analysis revealed that StTdcD possesses broad ligand specificity and could be activated by various SCFAs (propionate > acetate approximate to butyrate), nucleotides (ATP approximate to GTP > CTP approximate to TTP; dATP > dGTP > dCTP) and metal ions (Mg2+ approximate to Mn2+ > Co2+). Inhibition of StTdcD by tricarboxylic acid (TCA) cycle intermediates such as citrate, succinate, alpha-ketoglutarate and malate suggests that the enzyme could be under plausible feedback regulation. Crystal structures of StTdcD bound to PO4 (phosphate), AMP, ATP, Ap4 (adenosine tetraphosphate), GMP, GDP, GTP, CMP and CTP revealed that binding of nucleotide mainly involves hydrophobic interactions with the base moiety and could account for the broad biochemical specificity observed between the enzyme and nucleotides. Modeling and site-directed mutagenesis studies suggest Ala88 to be an important residue involved in determining the rate of catalysis with SCFA substrates. Molecular dynamics simulations on monomeric and dimeric forms of StTdcD revealed plausible open and closed states, and also suggested role for dimerization in stabilizing segment 235-290 involved in interfacial interactions and ligand binding. Observation of an ethylene glycol molecule bound sufficiently close to the gamma-phosphate in StTdcD complexes with triphosphate nucleotides supports direct in-line phosphoryl transfer. (C) 2013 Elsevier B.V. All rights reserved.

Mechanistic Insights into a Non-Classical Diffusion Pathway for the Formation of Hollow Intermetallics: A Route to Multicomponent Hollow Structures

Hollow nanostructures are used for various applications including catalysis, sensing, and drug delivery. Methods based on the Kirkendall effect have been the most successful for obtaining hollow nanostructures of various multicomponent systems. The classical Kirkendall effect relies on the presence of a faster diffusing species in the core; the resultant imbalance in flux results in the formation of hollow structures. Here, an alternate non-Kirkendall mechanism that is operative for the formation of hollow single crystalline particles of intermetallic PtBi is demonstrated. The synthesis method involves sequential reduction of Pt and Bi salts in ethylene glycol under microwave irradiation. Detailed analysis of the reaction at various stages indicates that the formation of the intermetallic PtBi hollow nanoparticles occurs in steps. The mechanistic details are elucidated using control experiments. The use of microwave results in a very rapid synthesis of intermetallics PtBi that exhibits excellent electrocatalytic activity for formic acid oxidation reaction. The method presented can be extended to various multicomponent systems and is independent of the intrinsic diffusivities of the species involved.

Pr6O11 micro-spherical nano-assemblies: microwave-assisted synthesis, characterization and optical properties

We report the synthesis of Pr6O11 microspheres self-assembled from ultra-small nanocrystals formed by the microwave irradiation of a solution of a salt of Pr in ethylene glycol (EG). The as-prepared product consists of microspheres measuring 200 to 500 nm in diameter and made of <5 nm nano-crystallites. The surface of these microspheres/nanocrystals is covered/capped with an organic layer of ethylene glycol as shown by TEM analysis and confirmed by IR spectroscopy measurements. The as-prepared product shows blue-green emission under excitation, which changes to orange-red when the product is annealed in air at 600 degrees C for 2 h. This change in luminescence behaviour can be attributed to presence of ethylene glycol layer in the as-prepared product. The samples were characterized by X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM), IR Spectroscopy (IR), transmission electron microscopy (TEM), and thermogravimetric analysis (TGA). (C) 2013 Elsevier B.V. All rights reserved.

Identification of miRNAs from French bean (Phaseolus vulgaris) under low nitrate stress

Objective: In this study, we report the role of miRNAs involved under nitrogen starvation from widely grown vegetable crop, French bean. In recent years, a great deal of attention has been paid to the elucidation of miRNAs involved in low nitrate stress. Methods: To identify miRNAs expressed under stress, cDNA libraries were analyzed. Results: We reported the nine potential miRNAs with 67 targets involved in nutrient transporters and other stress specific genes. Among the miRNA sequences obtained 6 sequences belong to miR172 family, one with miR169. RT-PCR analysis of expression of miR172 family was induced upon low nitrate stress while miR169 family was repressed. In addition, Pvu-SN7b and Pvu-miR16 may be new members of miRNA172 and miR169 families, respectively. Conclusion: The targets of Pvu-SN7b were major protein kinases, one among which is the Protein Kinase CK2. CK2 Kinase is found to involve in transcription-directed signaling, gene control and cell-cycle regulation. Other targets of Pvu-SN7b were involved in DNA-dependent transcription regulation, photo-periodism, calcium-mediated signaling. Pvu-miR16 targets Thymidine kinase, the key enzyme of deoxy-nucleotide synthesis. The cleavage of these targets affects cell proliferation there by affecting nodule formation. Pvu-miR8 inhibits translation of its target protein Pre-protein translocase, a membrane-bound protein transporter involved in trans-membrane protein transportation. Together these results denote the response and role of miRNAs to nitrate-limiting conditions in French bean.

Energy funneling and macromolecular conformational dynamics: a 2D Raman correlation study of PEG melting

Cascading energy landscapes through funneling has been postulated as a mechanistic route for achieving the lowest energy configuration of a macromolecular system (such as proteins and polymers). In particular, understanding the molecular mechanism for the melting and crystallization of polymers is a challenging fundamental question. The structural modifications that lead to the melting of poly(ethylene glycol) (PEG) are investigated here. Specific Raman bands corresponding to different configurations of the PEG chain have been identified, and the molecular structural dynamics of PEG melting have been addressed using a combination of Raman spectroscopy, 2D Raman correlation and density functional theory (DFT) calculations. The melting dynamics of PEG have been unambiguously explained along the C-O bond rotation coordinate.

Selenium in Diketopyrrolopyrrole-based Polymers: Influence on Electronic Properties and Charge Carrier Mobilities

Diketopyrrolopyrrole (DPP)-based pi-conjugated copolymers with thiophene have exceptionally high electron mobilities. This paper investigates electronic properties and charge carrier mobilities of selenophene containing analogues. Two new copolymers, with alternating thiophene DPP (TDPP) and selenophene DPP (SeDPP) units, were synthesized. Two side-chains, hexyl (Hex) and triethylene glycol (TEG) were employed, yielding polymers designated as PTDPPSeDPP-Hex and PTDPPSeDPP-TEG. Selenophene systems have smaller band gaps, with concomitant enhancement of the stability of the reduced state. For both polymers, ambipolar mobilities were observed in organic field-effect transistors (OFET). Grazing incidence X-ray diffraction (GIXD) data indicates preferential edge-on orientation of PTDPPSeDPP-TEG, which leads to superior charge transport properties of the TEG substituted polymer, as compared to its Hex analogue. Time-dependent-density functional theory (TDDFT) calculations corroborate the decrease in the optical band gap with the inclusion of selenophene. Ambipolar charge transport is rationalized by exceptionally wide conduction bands. Delta SCF calculations confirm the larger electron affinity, and therefore the greater stability, of the reduced form of the selenophene-containing DPP polymer in presence of chloroform.

Use of side-chain for rational design of n-type diketopyrrolopyrrole-based conjugated polymers: what did we find out?

The primary role of substituted side chains in organic semiconductors is to increase their solubility in common organic solvents. In the recent past, many literature reports have suggested that the side chains play a critical role in molecular packing and strongly impact the charge transport properties of conjugated polymers. In this work, we have investigated the influence of side-chains on the charge transport behavior of a novel class of diketopyrrolopyrrole (DPP) based alternating copolymers. To investigate the role of side-chains, we prepared four diketopyrrolopyrrole-diketopyrrolopyrrole (DPP-DPP) conjugated polymers with varied side-chains and carried out a systematic study of thin film microstructure and charge transport properties in polymer thin-film transistors (PTFTs). Combining results obtained from grazing incidence X-ray diffraction (GIXD) and charge transport properties in PTFTs, we conclude side-chains have a strong influence on molecular packing, thin film microstructure, and the charge carrier mobility of DPP-DPP copolymers. However, the influence of side-chains on optical properties was moderate. The preferential ``edge-on'' packing and dominant n-channel behavior with exceptionally high field-effect electron mobility values of >1 cm(2) V-1 s(-1) were observed by incorporating hydrophilic (triethylene glycol) and hydrophobic side-chains of alternate DPP units. In contrast moderate electron and hole mobilities were observed by incorporation of branched hydrophobic side-chains. This work clearly demonstrates that the subtle balance between hydrophobicity and hydrophilicity induced by side-chains is a powerful strategy to alter the molecular packing and improve the ambipolar charge transport properties in DPP-DPP based conjugated polymers. Theoretical analysis supports the conclusion that the side-chains influence polymer properties through morphology changes, as there is no effect on the electronic properties in the gas phase. The exceptional electron mobility is at least partially a result of the strong intramolecular conjugation of the donor and acceptor as evidenced by the unusually wide conduction band of the polymer.

Ag nanoparticles-anchored reduced graphene oxide catalyst for oxygen electrode reaction in aqueous electrolytes and also a non-aqueous electrolyte for Li-O-2 cells

Silver nanoparticles-anchored reduced graphene oxide (Ag-RGO) is prepared by simultaneous reduction of graphene oxide and Ag+ ions in an aqueous medium by ethylene glycol as the reducing agent. Ag particles of average size of 4.7 nm were uniformly distributed on the RGO sheets. Oxygen reduction reaction (ORR) is studied on Ag-RGO catalyst in both aqueous and non-aqueous electrolytes by using cyclic voltammetry and rotating disk electrode techniques. As the interest in non-aqueous electrolyte is to study the catalytic performance of Ag-RGO for rechargeable Li-O-2 cells, these cells are assembled and characterized. Li-O-2 cells with Ag-RGO as the oxygen electrode catalyst are subjected to charge-discharge cycling at several current densities. A discharge capacity of 11 950 mA h g(-1) (11.29 mA h cm(-2)) is obtained initially at low current density. Although there is a decrease in the capacity on repeated discharge-charge cycling initially, a stable capacity is observed for about 30 cycles. The results indicate that Ag-RGO is a suitable catalyst for rechargeable Li-O-2 cells.

Strategy for Enhancing the Dielectric Constant of Organic Semiconductors Without Sacrificing Charge Carrier Mobility and Solubility

Current organic semiconductors for organic photovoltaics (OPV) have relative dielectric constants (relative permittivities, epsilon(r)) in the range of 2-4. As a consequence, Coulombically bound electron-hole pairs (excitons) are produced upon absorption of light, giving rise to limited power conversion efficiencies. We introduce a strategy to enhance epsilon(r) of well-known donors and acceptors without breaking conjugation, degrading charge carrier mobility or altering the transport gap. The ability of ethylene glycol (EG) repeating units to rapidly reorient their dipoles with the charge redistributions in the environment was proven via density functional theory (DFT) calculations. Fullerene derivatives functionalized with triethylene glycol side chains were studied for the enhancement of epsilon(r) together with poly(p-phenylene vinylene) and diketo-pyrrolopyrrole based polymers functionalized with similar side chains. The polymers showed a doubling of epsilon(r) with respect to their reference polymers in identical backbone. Fullerene derivatives presented enhancements up to 6 compared with phenyl-C-61-butyric acid methyl ester (PCBM) as the reference. Importantly, the applied modifications did not affect the mobility of electrons and holes and provided excellent solubility in common organic solvents.

Inhibition of ERK and proliferation in NK cell lines by soluble HLA-E released from Japanese encephalitis virus infected cells

Productive infection of human endothelial cells with Japanese encephalitis virus (JEV), a single stranded RNA virus induces shedding of sHLA-E. We show here that sHLA-E that is released upon infection with this flavivirus can inhibit IL-2 and PMA mediated ERK 1/2 phosphorylation in two NK cell lines, Nishi and NKL. Virus infected or IFN-gamma treated cell culture supernatants containing sHLA-E were found to partially inhibit IL-2 mediated induction of CD25 molecules on NKL cells. It was also found that sHLA-E could inhibit IL-2 induced H-3]-thymidine incorporation suggesting that, similar to cell surface expressed HLA-E, sHLA-E could also inhibit NK cell responses. Hence JEV-induced shedding of sHLA-E needs further investigation to better understand immune responses in JEV infections since it may have a role in viral evasion of NK cell responses. (C) 2014 Elsevier B.V. All rights reserved.

Quantification of the Particle Size and Stability of Graphene Oxide in a Variety of Solvents

The exceptional solution processing potential of graphene oxide (GO) is always one of its main advantages over graphene in terms of its industrial relevance in coatings, electronics, and energy storage. However, the presence of a variety of functional groups on the basal plane and edges of GO makes understanding suspension behavior in aqueous and organic solvents, a major challenge. Acoustic spectroscopy can also measure zeta potential to provide unique insight into flocculating, meta-stable, and stable suspensions of GO in deionized water and a variety of organic solvents (including ethanol, ethylene glycol, and mineral oil). As expected, a match between solvent polarity and the polar functional groups on the GO surface favors stable colloidal suspensions accompanied by a smaller aggregate size tending toward disperse individual flakes of GO. This work is significant since it describes the characteristics of GO in solution and its ability to act as a precursor for graphene-based materials.

Porous Flower-like alpha-Fe2O3 Nanostructure: A High Performance Anode Material for Lithium-ion Batteries

Porous flower-like alpha-Fe2O3 nanostructures have been synthesized by ethylene glycol mediated iron alkoxide as an intermediate and studied as an anode material of Li-ion battery. The iron alkoxide precursor is heated at different temperatures from 300 to 700 degrees C. The alpha-Fe2O3 samples possess porosity and high surface area. There is a decrease in pore volume as well as surface area by increasing the preparation temperature. The reversible cycling properties of the alpha-Fe2O3 nanostructures have been evaluated by cyclic voltammetry, galvanostatic charge discharge cycling, and galvanostatic intermittent titration measurements at ambient temperature. The initial discharge capacity values of 1063, 1168,1183, 1152 and 968 mAh g(-1) at a specific current of 50 mA g(-1) are obtained for the samples prepared at 300, 400, 500, 600 and 700 degrees C, respectively. The samples prepared at 500 and 600 degrees C exhibit good cycling performance with high rate capability. The high rate capacity is attributed to porous nature of the materials. As the iron oxides are inexpensive and environmental friendly, the alpha-Fe2O3 has potential application as anode material for rechargeable Li batteries. (C) 2015 Elsevier Ltd. All rights reserved.

Periodically Grafted Amphiphilic Copolymers: Effects of Steric Crowding and Reversal of Amphiphilicity

Two series of periodically clickable polyesters were prepared; one of them carries alkylene segments along its backbone, whereas the other carries poly(ethylene glycol) (PEG) segments. These polyesters were clicked with either MPEG-350 azide or docosyl (C22) azide to yield periodically grafted amphiphilic copolymers (PGACs) carrying either flexible hydrophilic or crystallizable hydrophobic backbone segments. The immiscibility between hydrocarbon and PEG segments causes both of these systems to fold in either a zigzag or hairpin-like conformation; the hairpin-like conformation appears to be preferred when flexible PEG segments are present in the backbone. The folded chains further reorganize in the solid state to develop a lamellar morphology that permits the collocation of the PEG and hydrocarbon (HC) segments within alternate domains; evidence for the self-segregation was gained from DSC, SAXS, and AFM studies. SAXS studies revealed the formation of an extended lamellar structure, whereas AFM images showed uniform layered morphology with layer heights that matched reasonably well with the interlamellar spacing obtained from the SAXS study. Labeling One representative PGAC, carrying crystallizable long alkylene segments in the backbone and pendant PEG-350 side chains, with a small mole fraction of pyrene fluorophore permitted the examination of the conformational transition that occurs upon going from a good to a poor solvent; this single-chain folded conformation, we postulate, is the intermediate that organizes into the lamellar morphology.