New La2CuO4 derivatives La(2-2x)Sr(2x)Cu(1-x)M(x)O(4) (M=Ti, Mn, Fe, or Ru): A study of linear Cu-O-M electronic interaction in two dimensions

Oxides of the general formula La2-2xSr2xCu1-xII,M(x)(IV)O(4) (M = Ti, Mn, Fe, or Ru), crystallizing in the tetragonal K,NIF, structure, have been synthesized. For M=Ti, only the x=0,5 member could be prepared, while for M=Mn and Fe, the composition range is 0or M=Ru, the composition range is 0or equal to 0.5. There is no evidence for an ordering of Cu(II) and M(IV) in the x = 0.5 members. While the members of the M=Ti, Mn, and Ru series are semiconducting/insulating, the members of the M=Fe series are metallic, showing a broad metal-semiconductor transition around 100 K for Oor equal to 0.15 that is possibly related to a Cu(II)-O-Fe(IV) <--> Cu(III)-O-Fe(III) valence degeneracy. Increasing the strontium content at the expense of lanthanum in La2-2xSr2xCu1-xFexO4 for x less than or equal to 0.20 renders the samples metallic but not superconducting. (C) 1997 Academic Press.

Thermal analysis studies on hydroxobridged homo and hetero trinuclear cobalt(III) complexes

The synthesis and thermal analysis studies of several hydroxobridged homo and hetero trinuclear cobalt(III) complexes are reported. The complexes are of the type [M(H2O)(x) {(OH)(2)Co(en)(2)}(2)](SO4)(2). nH(2)O and [M(H2O)(x){(OH)(2)Co(NH3)(4)}(2)] (SO4)(2). nH(2)O where en denotes ethylenediamine and M =Co(II), Ni(II), Cu(II) and Zn(II) with x=0 for Cu(II), and 2 for other metal ions, and n =3, 4 or 5. The TG and DTA studies of these compounds show that one or more intermediate compounds are formed in each case before the metal oxides are produced.

Characterization of RNA polymerase III transcription factor TFIIIC from the mulberry silkworm, Bombyx mori

Fractionation of nuclear extracts from posterior silk glands of mulberry silkworm Bombyx mori. resolved the transcription factor TFIIIC into two components (designated here as TFIIIC and TFIIIC1) as in HeLa cell nuclear extracts. The reconstituted transcription of tRNA genes required the presence of both components. The affinity purified TFIIIC is a heteromeric complex comprising of five subunits ranging from 44 to 240 kDa. Of these, the 51-kDa subunit could be specifically crosslinked to the B box of tRNA(1)(Gly). Purified swTFIIIC binds to the B box sequences with an affinity in the same range as of yTFIIIC or hTFIIIC2. Although an histone acetyl transferase (HAT) activity was associated with the TFIIIC fractions during the initial stages of purification. the HAT activity, unlike the human TFIIIC preparations, was separated at the final DNA affinity step. The tRNA transcription from DNA template was independent of HAT activity but the repressed transcription from chromatin template could be partially restored by external supplementation of the dissociated HAT activity. This is the first report on the purification and characterization of TFIIIC from insect systems.

Prevalence of, and antigenic variation in, serotype G10 rotaviruses and detection of serotype G3 strains in diarrheic calves: Implications for the origin of G10P11 or P11 type reassortant asymptomatic strains in newborn children in India

Previous studies have shown predominant association of G10P11 type bovine rotavirus-derived reassortant strains with asymptomatic infections in newborn children in India. To understand the epidemiological and genetic basis for the origin of these strains in humans, the relative frequencies of different serotypes among bovine rotaviruses (BRVs) isolated from southern, western and central regions of the country were determined by subgroup and serotype analysis as well as nucleotide (nt) sequence analysis of the genes encoding the outer capsid proteins VP4 and VP7. Since the human G10P11 asymptomatic neonatal strain I321 possessed NSP1 from a human rotavirus, to determine its genetic origin in the bovine strains, comparative analysis of partial gene sequences from representative G10P11 strains was also carried out. The following observations were of great epidemiological significance, (i) G10P11 strains predominated in all the three regions with frequencies ranging between 55.6% and 85.2%. In contrast to the high prevalence of G6 strains in other countries, only one G6 strain was detected in this study and G8 strains represented 5.8% of the isolates, (ii) among the G10 strains, in serotyping ELISA, four patterns of reactivity were observed that appeared to correlate with the differences in electropherotypic patterns and amino acid (aa) sequence of the VP7, (iii) surprisingly, strains belonging to serotype G3 were detected more frequently (10.7%) than those of serotypes G6 and G8 combined, while strains representing the new serotype (G15) were observed in a single farm in Bangalore, and (iv) about 3.9% of the isolates were nontypeable as they exhibited high cross-reactivity to the serotyping MAbs used in the study. Comparative analysis of the VP7 gene sequence from the prototype G3 MAb-reactive bovine strain J63 revealed greatest sequence relatedness (87.6% nt and 96.0% aa) with that of serotype G3 rhesus-monkey strain RRV. It also exhibited high sequence homology with the VP7 from several animal and animal rotavirus-related human G3 strains (Simian SA11; equine ERV316 and FI-14. canine CU-1 and K9; porcine 4F; Feline Cat2 and human HCR3, YO and AU1). Partial nucleotide sequence analysis of the NSP1 gene of J63 showed greatest nt sequence homology (95.9%) to the NSP1 gene allele of the Indian G8 strain, isolated from a diarrheic child, which is likely to have been transmitted directly from cattle and 92.6% homology to that of the bovine G8 strain A5-10 suggesting the likely origin of J63 by gene reassortment between a bovine G8 strain and a G3 animal strain. Prevalence of G10P11 strains in cattle and G10P11 or P11 type reassortant strains in asymptomatic neonates as well as detection of G8P[1] strains in diarrheic children support our hypothesis for bidirectional transmission of rotaviruses between humans and cattle and origin of novel strains catalyzed by the age-old traditions and socio-economic conditions in India.

Mechanistic insights into type III restriction enzymes

Type III restriction-modification (R-M) enzymes need to interact with two separate unmethylated DNA sequences in indirectly repeated, head-to-head orientations for efficient cleavage to occur at a defined location next to only one of the two sites. However, cleavage of sites that are not in head-to-head orientation have been observed to occur under certain reaction conditions in vitro. ATP hydrolysis is required for the long-distance communication between the sites prior to cleavage. Type III R-M enzymes comprise two subunits, Res and Mod that form a homodimeric Mod(2) and a heterotetrameric Res(2)Mod(2) complex. The Mod subunit in M-2 or R2M2 complex recognizes and methylates DNA while the Res subunit in R2M2 complex is responsible for ATP hydrolysis, DNA translocation and cleavage. A vast majority of biochemical studies on Type III R-M enzymes have been undertaken using two closely related enzymes, EcoP1I and EcoP15I. Divergent opinions about how the long-distance interaction between the recognition sites exist and at least three mechanistic models based on 1D- diffusion and/or 3D-DNA looping have been proposed.

Timing and broad-band spectroscopy of 1A 1118-61 with Suzaku

We present a timing and broad-band pulse-phase-resolved spectral analysis of the transient Be X-ray binary pulsar 1A 1118-61 observed during its outburst in 2009 January using Suzaku observations. The Suzaku observations were made twice, once at the peak of the outburst, and the other 13 d later at its declining phase. Pulse profiles from both observations exhibit strong energy dependence with several peaks at low energies and a single peak above similar to 10 keV. A weak, narrow peak is detected at the main dip of the pulse profiles from both observations in the energy bands below 3 keV, indicating the presence of a phase-dependent soft excess in the source continuum. The broad-band energy spectrum of the pulsar could be fitted well with a partial covering cut-off power-law model and a narrow iron fluorescence line. We also detect a broad cyclotron feature at similar to 50 keV from both observations which is a feature common for accretion-powered pulsars with high magnetic field strength. The pulse-phase-resolved spectral analysis shows an increase in the absorption column density of the partial covering component, as well as variation in the covering fraction at the dips of the pulse profiles, which naturally explains energy dependence of the same. The cyclotron line parameters also show significant variation with pulse phase with an similar to 10 keV variation in the cyclotron line energy and a variation in depth by a factor of 3. This can be explained either as the effect of different viewing angles of the dipole field at different pulse phases, or due to a more complex underlying magnetic field geometry.

Evaluation of DNA binding, antioxidant and cytotoxic activity of mononuclear Co(III) complexes of 2-oxo-1,2-dihydrobenzoh]quinoline-3-carbaldehyde thiosemicarbazones

Four new 2-oxo-1,2-dihydrobenzoh]quinoline-3-carbaldehyde N-substituted thiosemicarbazone ligands (H-2-LR, where R = H, Me, Et or Ph) and their corresponding new cobalt(III) complexes have been synthesized and characterized. The structures of the complexes 2 and 3 were determined by single crystal X-ray diffraction analysis. The interactions of the new complexes with DNA were investigated by absorption, emission and viscosity studies which indicated that the complexes bind to DNA via intercalation. Antioxidant studies of the new complexes showed that the significant antioxidant activity against DPPH radical. In addition, the in vitro cytotoxicity of complexes 1-4 against A549 cell line was assayed which showed higher cytotoxic activity with lower IC50 values indicating their efficiency in killing the cancer cells even at very low concentrations. (C) 2012 Elsevier Masson SAS. All rights reserved.

A novel ``pro-sensitizer'' based sensing of enzymes using Tb(III) luminescence in a hydrogel matrix

Chemically synthesized ``pro-sensitizers'' release the sensitizer in the presence of lipase or beta-glucosidase, triggering a significant luminescence response from a lanthanide based hydrogel.

Synthesis, antimicrobial, DNA-binding and photonuclease studies of Cobalt(III) and Nickel(II) Schiff base complexes

New metal complexes of the type M(nih)(L)](PF6)(n)center dot xAH(2)O and M(nih)(2)](PF6)center dot xH(2)O (where M = Co(III) or Ni(II), L = 1,10-phenanthroline (phen)/or 2,2' bipyridine (bpy), nih = 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone, n = 2 or 1 and x = 3 or 2) have been synthesized and characterized by elemental analysis, magnetic, IR and H-1 NMR spectral data. The electronic and magnetic moment 2.97-3.07 B.M. data infers octahedral geometry for all the complexes. The IR data reveals that Schiff base (nih) form coordination bond with the metal ion through azomethine-nitrogen, phenolic-oxygen and carbonyl-oxygen in a tridentate fashion. In addition, DNA-binding properties of these six metal complexes were investigated using absorption spectroscopy, viscosity measurements and thermal denaturation methods. The results indicated that the nickel(II) complex strongly bind with calf-thymus DNA with intrinsic DNA binding constant K-b value of 4.9 x 10(4) M-1 for (3), 4.2 x 10(4) M-1 for (4), presumably via an intercalation mechanism compared to cobalt(III) complex with K-b value of 4.6 x 10(4) M-1 (1) and 4.1 x 10(4) M-1 (2). The DNA Photoclevage experiment shows that, the complexes act as effective DNA cleavage agent. (C) 2012 Elsevier B.V. All rights reserved.

Biotin-conjugated tumour-targeting photocytotoxic iron(III) complexes

Iron(III) complexes FeL(B)] (1-4) of a tetradentate phenolate-based ligand (H3L) and biotin-conjugated dipyridophenazine bases (B), viz. 7-aminodipyrido 3,2-a: 2',3'-c]-phenazine (dppza in 1), (N-dipyrido3,2-a: 2',3'-c]-phenazino) amidobiotin (dppzNB in 2), dipyrido 3,2-a: 2',3'-c]-phenazine-11-carboxylic acid (dppzc in 3) and 2-((2-biotinamido) ethyl) amidodipyrido 3,2-a: 2',3'-c]-phenazine (dppzCB in 4) are prepared, characterized and their interaction with streptavidin and DNA and their photocytotoxicity and cellular uptake in various cells studied. The high-spin iron(III) complexes display Fe(III)/Fe(II) redox couple near -0.7V versus saturated calomel electrode in dimethyl sulfoxide-0.1M tetrabutylammonium perchlorate. The complexes show non-specific interaction with DNA as determined from the binding studies. Complexes with appended biotin moiety show similar binding to streptavidin as that of free biotin, suggesting biotin conjugation to dppz does not cause any loss in its binding affinity to streptavidin. The photocytotoxicity of the complexes is tested in HepG2, HeLa and HEK293 cell lines. Complex 2 shows higher photocytotoxicity in HepG2 cells than in HeLa or HEK293, forming reactive oxygen species. This effect is attributed to the presence of overexpressed sodium-dependent multi-vitamin transporters in HepG2 cells. Microscopic studies in HepG2 cells show internalization of the biotin complexes 2 and 4 essentially occurring by receptor-mediated endocytosis, which is similar to that of native biotin and biotin fluorescein isothiocyanate conjugate.

Inhibition of cancer cell proliferation and apoptosis-inducing activity of fungal taxol and its precursor baccatin III purified from endophytic Fusarium solani

Background: Taxol (generic name paclitaxel), a plant-derived antineoplastic agent, used widely against breast, ovarian and lung cancer, was originally isolated from the bark of the Pacific yew, Taxus brevifolia. The limited supply of the drug has prompted efforts to find alternative sources, such as chemical synthesis, tissue and cell cultures of the Taxus species both of which are expensive and yield low levels. Fermentation processes with microorganisms would be the methods of choice to lower the costs and increase yields. Previously we have reported that F. solani isolated from T. celebica produced taxol and its precursor baccatin III in liquid grown cultures J Biosci 33: 259-67, 2008. This study was performed to evaluate the inhibition of proliferation and induction of apoptosis of cancer cell lines by the fungal taxol and fungal baccatin III of F. solani isolated from T. celebica. Methods: Cell lines such as HeLa, HepG2, Jurkat, Ovcar3 and T47D were cultured individually and treated with fungal taxol, baccatin III with or without caspase inhibitors according to experimental requirements. Their efficacy on apoptotic induction was examined. Results: Both fungal taxol and baccatin III inhibited cell proliferation of a number of cancer cell lines with IC50 ranging from 0.005 to 0.2 mu M for fungal taxol and 2 to 5 mu M for fungal baccatin III. They also induced apoptosis in JR4-Jurkat cells with a possible involvement of anti-apoptotic Bcl2 and loss in mitochondrial membrane potential, and was unaffected by inhibitors of caspase-9,-2 or -3 but was prevented in presence of caspase-10 inhibitor. DNA fragmentation was also observed in cells treated with fungal taxol and baccatin III. Conclusions: The cytotoxic activity exhibited by fungal taxol and baccatin III involves the same mechanism, dependent on caspase-10 and membrane potential loss of mitochondria, with taxol having far greater cytotoxic potential.

Type III restriction-modification enzymes: a historical perspective

Restriction endonucleases interact with DNA at specific sites leading to cleavage of DNA. Bacterial DNA is protected from restriction endonuclease cleavage by modifying the DNA using a DNA methyltransferase. Based on their molecular structure, sequence recognition, cleavage position and cofactor requirements, restriction-modification (R-M) systems are classified into four groups. Type III R-M enzymes need to interact with two separate unmethylated DNA sequences in inversely repeated head-to-head orientations for efficient cleavage to occur at a defined location (25-27 bp downstream of one of the recognition sites). Like the Type I R-M enzymes, Type III R-M enzymes possess a sequence-specific ATPase activity for DNA cleavage. ATP hydrolysis is required for the long-distance communication between the sites before cleavage. Different models, based on 1D diffusion and/or 3D-DNA looping, exist to explain how the long-distance interaction between the two recognition sites takes place. Type III R-M systems are found in most sequenced bacteria. Genome sequencing of many pathogenic bacteria also shows the presence of a number of phase-variable Type III R-M systems, which play a role in virulence. A growing number of these enzymes are being subjected to biochemical and genetic studies, which, when combined with ongoing structural analyses, promise to provide details for mechanisms of DNA recognition and catalysis.

Terbium(III)-cholate functionalized vesicles as luminescent indicators for the enzymatic conversion of dihydroxynaphthalene diesters

The phosphorescence intensity of unilamellar DOPC vesicles with embedded Tb3+-cholate complexes depends on the concentration of dihydroxynaphthalene (DHN) as sensitizer in solution. This was used to monitor the enzymatic conversion of DHN esters or DHN glucosides by enzymes in aqueous buffered solution.

Remarkable visible light-triggered cytotoxicity of mitochondria targeting mixed-ligand cobalt(III) complexes of curcumin and phenanthroline bases binding to human serum albumin

Six new mixed-ligand cobalt(III) complexes of formulation Co(N-N)(2)(O-O)](ClO4)(2) (1-6), where N-N is a N,N-donor phenanthroline base, namely, 1,10-phenanthroline (phen in 1, 2), dipyrido3,2-d:2',3'-f] quinoxaline (dpq in 3, 4), and dipyrido3,2-a:2',3'-c]phenazine (dppz in 5, 6), O-O is acetylacetonate (acac in 1, 3, 5) or curcumin (bis(4-hydroxy-3-methoxyphenyl)-1,6-diene-3,5-dione, cur in 2, 4, 6), have been synthesized and characterized. The X-ray crystal structures of complex 1 (as PF6- salt, 1a) and 3 show distorted octahedral geometries formed by the CoN4O2 core. The complexes 1, 3 and 5 having the simple acac ligand are prepared as control species to understand the role of curcumin. The optimized geometries and the frontier orbitals of the curcumin complexes 2, 4, and 6 are obtained from the DFT calculations. The complexes 2, 4, and 6 having the photoactive curcumin moiety display an absorption band in the visible region near 420 nm and show remarkable photocytotoxicity in HeLa cancer cells with respective IC50 values of 7.4 mu M, 5.1 mu M and 1.6 mu M while being much less toxic in dark. MTT assay using complex 6 shows that it is not significantly photocytotoxic to MCF-10A normal cells. The control complexes having the acac ligand are non-toxic both in the presence and absence of light. The cell death is apoptotic in nature and triggered by the photogeneration of reactive oxygen species. Fluorescence imaging experiments on HeLa cells reveals that complex 6 accumulated primarily inside the mitochondria. Human serum albumin (HSA) binding experiments show that the complexes bind HSA with good affinity, but 6 binds with the highest affinity, with a K-b value of 9.8 x 10(5) M-1. Thus, complex 6 with its negligible toxicity in the dark and in normal cells but remarkable toxicity in visible light holds significant photochemotherapeutic potential.

Significant photocytotoxic effect of an iron(III) complex of a Schiff base ligand derived from vitamin B-6 and thiosemicarbazide in visible light

Iron(III)-Schiff base complexes, namely, Fe(tsc-py)(2)](NO3) (1), Fe(tsc-acpy)(2)](NO3) (2) and Fe(tsc-VB6)(2)](NO3) (3), where tsc-py, tsc-acpy and tsc-VB6 are the respective Schiff bases derived from thiosemicarbazide (tsc) and pyridine-2-aldehyde (tsc-py), 2-acetyl pyridine (tsc-acpy) and vitamin B-6 (pyridoxal, tsc-VB6), have been prepared, structurally characterized and their photocytotoxicity studied in cancer HeLa cells. The single crystal X-ray structures of the complexes 1 and 2 show a distorted octahedral geometry formed by the FeN4S2 core. The low-spin and 1 : 1 electrolytic complexes display a broad absorption band in the visible region. Complexes 1 and 2, without any VB6 moiety are not cytotoxic under light or dark conditions. Complex 3 is significantly photocytotoxic under visible light of 400-700 nm giving an IC50 value of 22.5 mu M in HeLa cells with no dark toxicity (IC50 > 100 mu M). The photo-induced cell death is attributable to apoptotic pathways involving photo-assisted generation of intracellular ROS. The observed photocytotoxicity of complex 3 could be the result of its better photosensitizing property combined with its enhanced uptake into cancer cells via a VB6 transporting membrane carrier (VTC) mediated diffusion pathway due to the presence of the VB6 moiety compared to the two non-vitamin B-6 analogues, complexes 1 and 2.