active metarhodopsin ii: Topics by Science.gov

Sample records for active metarhodopsin ii

Metarhodopsin control by arrestin, light-filtering screening pigments, and visual pigment turnover in invertebrate microvillar photoreceptors.

PubMed

Stavenga, Doekele G; Hardie, Roger C

2011-03-01

The visual pigments of most invertebrate photoreceptors have two thermostable photo-interconvertible states, the ground state rhodopsin and photo-activated metarhodopsin, which triggers the phototransduction cascade until it binds arrestin. The ratio of the two states in photoequilibrium is determined by their absorbance spectra and the effective spectral distribution of illumination. Calculations indicate that metarhodopsin levels in fly photoreceptors are maintained below ~35% in normal diurnal environments, due to the combination of a blue-green rhodopsin, an orange-absorbing metarhodopsin and red transparent screening pigments. Slow metarhodopsin degradation and rhodopsin regeneration processes further subserve visual pigment maintenance. In most insect eyes, where the majority of photoreceptors have green-absorbing rhodopsins and blue-absorbing metarhodopsins, natural illuminants are predicted to create metarhodopsin levels greater than 60% at high intensities. However, fast metarhodopsin decay and rhodopsin regeneration also play an important role in controlling metarhodopsin in green receptors, resulting in a high rhodopsin content at low light intensities and a reduced overall visual pigment content in bright light. A simple model for the visual pigment-arrestin cycle is used to illustrate the dependence of the visual pigment population states on light intensity, arrestin levels and pigment turnover.
Two different forms of metarhodopsin II: Schiff base deprotonation precedes proton uptake and signaling state.

PubMed

Arnis, S; Hofmann, K P

1993-08-15

Rhodopsin is a retinal protein and a G-protein-coupled receptor; it shares with both of these families the seven helix structure. To generate the G-interacting helix-loop conformation, generally identified with the 380-nm absorbing metarhodopsin II (MII) photoproduct, the retinal Schiff base bond to the apoprotein must be deprotonated. This occurs as a key event also in the related retinal proteins, sensory rhodopsins, and the proton pump bacteriorhodopsin. In MII, proton uptake from the aqueous phase must be involved as well, since its formation increases the pH of the aqueous medium and is accelerated under acidic conditions. In the native membrane, the pH effect matches MII formation kinetically, suggesting that intramolecular and aqueous protonation changes contribute in concert to the protein transformation. We show here, however, that proton uptake, as indicated by bromocresol purple, and Schiff base deprotonation (380-nm absorption change) show different kinetics when the protein is solubilized in suitable detergents. Our data are consistent with a two-step reaction:
Two different forms of metarhodopsin II: Schiff base deprotonation precedes proton uptake and signaling state.

PubMed Central

Arnis, S; Hofmann, K P

1993-01-01

Rhodopsin is a retinal protein and a G-protein-coupled receptor; it shares with both of these families the seven helix structure. To generate the G-interacting helix-loop conformation, generally identified with the 380-nm absorbing metarhodopsin II (MII) photoproduct, the retinal Schiff base bond to the apoprotein must be deprotonated. This occurs as a key event also in the related retinal proteins, sensory rhodopsins, and the proton pump bacteriorhodopsin. In MII, proton uptake from the aqueous phase must be involved as well, since its formation increases the pH of the aqueous medium and is accelerated under acidic conditions. In the native membrane, the pH effect matches MII formation kinetically, suggesting that intramolecular and aqueous protonation changes contribute in concert to the protein transformation. We show here, however, that proton uptake, as indicated by bromocresol purple, and Schiff base deprotonation (380-nm absorption change) show different kinetics when the protein is solubilized in suitable detergents. Our data are consistent with a two-step reaction: Images Fig. 6 PMID:8356093
Structure and function in rhodopsin: replacement by alanine of cysteine residues 110 and 187, components of a conserved disulfide bond in rhodopsin, affects the light-activated metarhodopsin II state.

PubMed Central

Davidson, F F; Loewen, P C; Khorana, H G

1994-01-01

A disulfide bond that is evidently conserved in the guanine nucleotide-binding protein-coupled receptors is present in rhodopsin between Cys-110 and Cys-187. We have replaced these two cysteine residues by alanine residues and now report on the properties of the resulting rhodopsin mutants. The mutant protein C110A/C187A expressed in COS cells resembles wild-type rhodopsin in the ground state. It folds correctly to bind 11-cis-retinal and form the characteristic rhodopsin chromophore. It is inert to hydroxylamine in the dark, and its stability to dark thermal decay is reduced, relative to that of the wild type, by a delta delta G not equal to of only -2.9 kcal/mol. Further, the affinities of the mutant and wild-type rhodopsins to the antirhodopsin antibody rho4D2 are similar, both in the dark and in light. However, the metarhodopsin II (MII) and MIII photointermediates of the mutant are less stable than those formed by the wild-type rhodopsin. Although the initial rates of transducin activation are the same for both mutant and wild-type MII intermediates at 4 degrees C, at 15 degrees C the MII photointermediate in the mutant decays more than 20 times faster than in wild type. We conclude that the disulfide bond between Cys-110 and Cys-187 is a key component in determining the stability of the MII structure and its coupling to transducin activation. PMID:8171030
Effect of dodecyl maltoside detergent on rhodopsin stability and function.

PubMed

Ramon, Eva; Marron, Jordi; del Valle, Luis; Bosch, Laia; Andrés, Anna; Manyosa, Joan; Garriga, Pere

2003-12-01

Detergent-solubilized bovine rhodopsin produces mixed detergent/lipid/protein micelles. The effect of dodecyl maltoside detergent on the thermal stability of dark-state rhodopsin, and upon formation of the different intermediates after rhodopsin photobleaching (metarhodopsin II and metarhodopsin III), and upon transducin activation has been studied. No significant effect is observed for the thermal stability of dark-state rhodopsin in the range of detergent concentrations studied, but a decrease in the stability of metarhodopsin II and an increase in metarhodopsin III formation is observed with decreasing detergent concentrations. The transducin activation process is also affected by the presence of detergent indicating that this process is dependent on the lipid micro-environment and membrane fluidity, and this stresses the importance of the native lipid environment in rhodopsin normal function.
Constitutive phospholipid scramblase activity of a G protein-coupled receptor

NASA Astrophysics Data System (ADS)

Goren, Michael A.; Morizumi, Takefumi; Menon, Indu; Joseph, Jeremiah S.; Dittman, Jeremy S.; Cherezov, Vadim; Stevens, Raymond C.; Ernst, Oliver P.; Menon, Anant K.

2014-10-01

Opsin, the rhodopsin apoprotein, was recently shown to be an ATP-independent flippase (or scramblase) that equilibrates phospholipids across photoreceptor disc membranes in mammalian retina, a process required for disc homoeostasis. Here we show that scrambling is a constitutive activity of rhodopsin, distinct from its light-sensing function. Upon reconstitution into vesicles, discrete conformational states of the protein (rhodopsin, a metarhodopsin II-mimic, and two forms of opsin) facilitated rapid (>10,000 phospholipids per protein per second) scrambling of phospholipid probes. Our results indicate that the large conformational changes involved in converting rhodopsin to metarhodopsin II are not required for scrambling, and that the lipid translocation pathway either lies near the protein surface or involves membrane packing defects in the vicinity of the protein. In addition, we demonstrate that β2-adrenergic and adenosine A2A receptors scramble lipids, suggesting that rhodopsin-like G protein-coupled receptors may play an unexpected moonlighting role in re-modelling cell membranes.
Fourier transform infrared studies of active-site-methylated rhodopsin. Implications for chromophore-protein interaction, transducin activation, and the reaction pathway.

PubMed Central

Ganter, U M; Longstaff, C; Pajares, M A; Rando, R R; Siebert, F

1991-01-01

Fourier transform infrared studies of active-site-methylated rhodopsin (ASMR) show that, as compared to unmodified rhodopsin, the photoreaction is almost unchanged up to the formation of lumirhodopsin. Especially, the deviations are much smaller than those observed for the corresponding intermediates of 13-desmethyl-rhodopsin. In metarhodopsin-I, larger alterations are present with respect to the three internal carboxyl groups. Similar deviations have been observed in meta-I of 13-desmethyl-rhodopsin. This indicates that, in agreement with our previous investigations, these carboxyl groups are located in close proximity to the chromophore. Because this latter pigment is capable, when bleached, of activating transducin, our data provide support for the earlier conclusion that deprotonation of the Schiff base is a prerequisite for transducin activation. The positions of the C = C and C - C stretching modes of the retinal suggest that the redshift observed in ASMR and its photoproducts can be explained by an increased distance of the Schiff base from the counterion(s). It is further shown that the photoreaction does not stop at metarhodopsin-I, but that this intermediate directly decays to a metarhodopsin-III-like species. PMID:2049524
Monomeric rhodopsin is the minimal functional unit required for arrestin binding.

PubMed

Tsukamoto, Hisao; Sinha, Abhinav; DeWitt, Mark; Farrens, David L

2010-06-11

We have tested whether arrestin binding requires the G-protein-coupled receptor be a dimer or a multimer. To do this, we encapsulated single-rhodopsin molecules into nanoscale phospholipid particles (so-called nanodiscs) and measured their ability to bind arrestin. Our data clearly show that both visual arrestin and beta-arrestin 1 can bind to monomeric rhodopsin and stabilize the active metarhodopsin II form. Interestingly, we find that the monomeric rhodopsin in nanodiscs has a higher affinity for wild-type arrestin binding than does oligomeric rhodopsin in liposomes or nanodiscs, as assessed by stabilization of metarhodopsin II. Together, these results establish that rhodopsin self-association is not required to enable arrestin binding. Copyright 2010 Elsevier Ltd. All rights reserved.
Alkylated hydroxylamine derivatives eliminate peripheral retinylidene Schiff bases but cannot enter the retinal binding pocket of light-activated rhodopsin.

PubMed

Piechnick, Ronny; Heck, Martin; Sommer, Martha E

2011-08-23

Besides Lys-296 in the binding pocket of opsin, all-trans-retinal forms adducts with peripheral lysine residues and phospholipids, thereby mimicking the spectral and chemical properties of metarhodopsin species. These pseudophotoproducts composed of nonspecific retinylidene Schiff bases have long plagued the investigation of rhodopsin deactivation and identification of decay products. We discovered that, while hydroxylamine can enter the retinal binding pocket of light-activated rhodopsin, the modified hydroxylamine compounds o-methylhydroxylamine (mHA), o-ethylhydroxylamine (eHA), o-tert-butylhydroxylamine (t-bHA), and o-(carboxymethyl)hydroxylamine (cmHA) are excluded. However, the alkylated hydroxylamines react quickly and efficiently with exposed retinylidene Schiff bases to form their respective retinal oximes. We further investigated how t-bHA affects light-activated rhodopsin and its interaction with binding partners. We found that both metarhodopsin II (Meta II) and Meta III are resistant to t-bHA, and neither arrestin nor transducin binding is affected by t-bHA. This discovery suggests that the hypothetical solvent channel that opens in light-activated rhodopsin is extremely stringent with regard to size and/or polarity. We believe that alkylated hydroxylamines will prove to be extremely useful reagents for the investigation of rhodopsin activation and decay mechanisms. Furthermore, the use of alkylated hydroxylamines should not be limited to in vitro studies and could help elucidate visual signal transduction mechanisms in the living cells of the retina. © 2011 American Chemical Society
The effect of phosphorylation on arrestin-rhodopsin interaction in the squid visual system.

PubMed

Robinson, Kelly A; Ou, Wei-Lin; Guan, Xinyu; Sugamori, Kim S; Bandyopadhyay, Abhishek; Ernst, Oliver P; Mitchell, Jane

2015-12-01

Invertebrate visual opsins are G protein-coupled receptors coupled to retinoid chromophores that isomerize reversibly between inactive rhodopsin and active metarhodopsin upon absorption of photons of light. The squid visual system has an arrestin protein that binds to metarhodopsin to block signaling to Gq and activation of phospholipase C. Squid rhodopsin kinase (SQRK) can phosphorylate both metarhodopsin and arrestin, a dual role that is unique among the G protein-coupled receptor kinases. The sites and role of arrestin phosphorylation by SQRK were investigated here using recombinant proteins. Arrestin was phosphorylated on serine 392 and serine 397 in the C-terminus. Unphosphorylated arrestin bound to metarhodopsin and phosphorylated metarhodopsin with similar high affinities (Kd 33 and 21 nM respectively), while phosphorylation of arrestin reduced the affinity 3- to 5-fold (Kd 104 nM). Phosphorylation of metarhodopsin slightly increased the dissociation of arrestin observed during a 1 hour incubation. Together these studies suggest a unique role for SQRK in phosphorylating both receptor and arrestin and inhibiting the binding of these two proteins in the squid visual system. Invertebrate visual systems are inactivated by arrestin binding to metarhodopsin that does not require receptor phosphorylation. Here we show that squid rhodopsin kinase phosphorylates arrestin on two serines (S392,S397) in the C-terminus and phosphorylation decreases the affinity of arrestin for squid metarhodopsin. Metarhodopsin phosphorylation has very little effect on arrestin binding but does increase arrestin dissociation. © 2015 International Society for Neurochemistry.
pH and rate of ‘dark’ events in toad retinal rods: test of a hypothesis on the molecular origin of photoreceptor noise

PubMed Central

Firsov, Mikhail L; Donner, Kristian; Govardovskii, Victor I

2002-01-01

Thermal activation of the visual pigment constitutes a fundamental constraint on visual sensitivity. Its electrical correlate in the membrane current of dark-adapted rods are randomly occurring discrete ‘dark events’ indistinguishable from responses to single photons. It has been proposed that thermal activation occurs in a small subpopulation of rhodopsin molecules where the Schiff base linking the chromophore to the protein part is unprotonated. On this hypothesis, rates of thermal activation should increase strongly with rising pH. The hypothesis has been tested by measuring the effect of pH changes on the frequency of discrete dark events in red rods of the common toad Bufo bufo. Dark noise was recorded from isolated rods using the suction pipette technique. Changes in cytoplasmic pH upon manipulations of extracellular pH were quantified by measuring, using fast single-cell microspectrophotometry, the pH-dependent metarhodopsin I-metarhodopsin II equilibrium and subsequent metarhodopsin III formation. These measurements show that, in the conditions of the electrophysiological experiments, changing perfusion pH from 6.5 to 9.3 resulted in a cytoplasmic pH shift from 7.6 to 8.5 that was readily sensed by the rhodopsin. This shift, which implies an 8-fold decrease in cytoplasmic [H+], did not increase the rate of dark events. The results contradict the hypothesis that thermal pigment activation depends on prior deprotonation of the Schiff base. PMID:11897853
Retinylidene ligand structure in bovine rhodopsin, metarhodopsin-I, and 10-methylrhodopsin from internuclear distance measurements using 13C-labeling and 1-D rotational resonance MAS NMR.

PubMed

Verdegem, P J; Bovee-Geurts, P H; de Grip, W J; Lugtenburg, J; de Groot, H J

1999-08-31

Rhodopsin is the G-protein coupled photoreceptor that initiates the rod phototransduction cascade in the vertebrate retina. Using specific isotope enrichment and magic angle spinning (MAS) NMR, we examine the spatial structure of the C10-C11=C12-C13-C20 motif in the native retinylidene chromophore, its 10-methyl analogue, and the predischarge photoproduct metarhodopsin-I. For the rhodopsin study 11-Z-[10,20-(13)C(2)]- and 11-Z-[11,20-(13)C(2)]-retinal were synthesized and incorporated into bovine opsin while maintaining a natural lipid environment. The ligand is covalently bound to Lys(296) in the photoreceptor. The C10-C20 and C11-C20 distances were measured using a novel 1-D CP/MAS NMR rotational resonance experimental procedure that was specifically developed for the purpose of these measurements [Verdegem, P. J. E., Helmle, M., Lugtenburg, J., and de Groot, H. J. M. (1997) J. Am. Chem. Soc. 119, 169]. We obtain r(10,20) = 0.304 +/- 0.015 nm and r(11,20) = 0.293 +/- 0.015 nm, which confirms that the retinylidene is 11-Z and shows that the C10-C13 unit is conformationally twisted. The corresponding torsional angle is about 44 degrees as indicated by Car-Parrinello modeling studies. To increase the nonplanarity in the chromophore, 11-Z-[10,20-(13)C(2)]-10-methylretinal and 11-Z-[(10-CH(3)), 13-(13)C(2)]-10-methylretinal were prepared and incorporated in opsin. For the resulting analogue pigment r(10,20) = 0.347 +/- 0.015 nm and r((10)(-)(CH)()3())(,)(13) = 0.314 +/- 0.015 nm were obtained, consistent with a more distorted chromophore. The analogue data are in agreement with the induced fit principle for the interaction of opsin with modified retinal chromophores. Finally, we determined the intraligand distances r(10,20) and r(11,20) also for the photoproduct metarhodopsin-I, which has a relaxed all-E structure. The results (r(10,20) >/= 0.435 nm and r(11,20) = 0.283 +/- 0.015 nm) fully agree with such a relaxed all-E structure, which further validates the 1-D
Energetics of primary processes in visula escitation: photocalorimetry of rhodopsin in rod outer segment membranes.

PubMed

Cooper, A; Converse, C A

1976-07-13

A sensitive technique for the direct calorimetric determination of the energetics of photochemical reactions under low levels of illumination, and its application to the study of primary processes in visula excitation, are described. Enthlpies are reported for various steps in the bleaching of rhodopsin in intact rod outer segment membranes, together with the heats of appropriate model reactions. Protonation changes are also determined calorimetrically by use of buffers with differing heats of proton ionization. Bleaching of rhodopsin is accompanied by significant uptake of heat energy, vastly in excess of the energy required for simple isomerization of the retinal chromophore. Metarhodopsin I formation involves the uptake of about 17 kcal/mol and no net change in proton ionization of the system. Formation of metarhodopsin II requires an additional energy of about 10 kcal/mol and involves the uptake on one hydrogen ion from solution. The energetics of the overall photolysis reaction, rhodopsin leads to opsin + all-trans-retinal, are pH dependent and involve the exposure of an additional titrating group on opsin. This group has a heat of proton ionization of about 12 kcal/mal, characteristic of a primary amine, but a pKa in the region of neutrality. We suggest that this group is the Schiff base lysine of the chromophore binding site of rhodopsin which becomes exposed on photolysis. The low pKa for this active lysine would result in a more stable retinal-opsin linkage, and might be induced by a nearby positively charged group on the protein (either arginine or a second lysine residue). This leads to a model involving intramolecular protonation of the Schiff base nitrogen in the retinal-opsin linkage of rhodopsin, which is consistent with the thermodynamic and spectroscopic properties of the system. We further propose that the metarhodopsin I leads to metarhodopsin II step in the bleaching sequence involves reversible hydrolysis of the Schiff base linkage in the
Quantification of arrestin-rhodopsin binding stoichiometry.

PubMed

Lally, Ciara C M; Sommer, Martha E

2015-01-01

We have developed several methods to quantify arrestin-1 binding to rhodopsin in the native rod disk membrane. These methods can be applied to study arrestin interactions with all functional forms of rhodopsin, including dark-state rhodopsin, light-activated metarhodopsin II (Meta II), and the products of Meta II decay, opsin and all-trans-retinal. When used in parallel, these methods report both the actual amount of arrestin bound to the membrane surface and the functional aspects of arrestin binding, such as which arrestin loops are engaged and whether Meta II is stabilized. Most of these methods can also be applied to recombinant receptor reconstituted into liposomes, bicelles, and nanodisks.
Effect of hydroxylamine on photon-like events during dark adaptation in toad rod photoreceptors.

PubMed Central

Leibrock, C S; Lamb, T D

1997-01-01

1. The suction pipette technique was used to investigate the recovery of toad rod photoreceptors following small bleaches of 0.2-3% of the rhodopsin. 2. The reduction in sensitivity and the increase in noise elicited by bleaches were measured, and from these measurements the underlying rate of occurrence of photon-like events was calculated as a function of time after the bleach. 3. Exposure to hydroxylamine solution was used to hasten the decomposition of the metarhodopsin photoproducts. The outer segment was exposed to 110 mM hydroxylamine in a low-Ca2+ Ringer solution for a period of 10-50 s beginning 10-17 min after the bleaching exposure. 4. By the time of the hydroxylamine exposure, the flash sensitivity and response kinetics had returned almost to normal, and were not significantly altered by the exposure. 5. Following hydroxylamine exposure, the rate of spontaneous photon-like events in the rods declined rapidly to near pre-bleach levels. 6. We conclude that hydroxylamine reduces the rate of occurrence of photon-like events induced by a bleach, and we postulate that this reduction results from the removal of metarhodopsin (most likely metarhodopsin II) from the outer segment. 7. Our results are consistent with a model in which photon-like events result from reversal of the reactions (phosphorylation and capping by arrestin) that lead to inactivation of the activated form of rhodopsin, Rh*. PMID:9174997
Tauroursodeoxycholic acid binds to the G-protein site on light activated rhodopsin.

PubMed

Lobysheva, E; Taylor, C M; Marshall, G R; Kisselev, O G

2018-05-01

The heterotrimeric G-protein binding site on G-protein coupled receptors remains relatively unexplored regarding its potential as a new target of therapeutic intervention or as a secondary site of action by the existing drugs. Tauroursodeoxycholic acid bears structural resemblance to several compounds that were previously identified to specifically bind to the light-activated form of the visual receptor rhodopsin and to inhibit its activation of transducin. We show that TUDCA stabilizes the active form of rhodopsin, metarhodopsin II, and does not display the detergent-like effects of common amphiphilic compounds that share the cholesterol scaffold structure, such as deoxycholic acid. Computer docking of TUDCA to the model of light-activated rhodopsin revealed that it interacts using similar mode of binding to the C-terminal domain of transducin alpha subunit. The ring regions of TUDCA made hydrophobic contacts with loop 3 region of rhodopsin, while the tail of TUDCA is exposed to solvent. The results show that TUDCA interacts specifically with rhodopsin, which may contribute to its wide-ranging effects on retina physiology and as a potential therapeutic compound for retina degenerative diseases. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
Time-resolved rhodopsin activation currents in a unicellular expression system.

PubMed Central

Sullivan, J M; Shukla, P

1999-01-01

The early receptor current (ERC) is the charge redistribution occurring in plasma membrane rhodopsin during light activation of photoreceptors. Both the molecular mechanism of the ERC and its relationship to rhodopsin conformational activation are unknown. To investigate whether the ERC could be a time-resolved assay of rhodopsin structure-function relationships, the distinct sensitivity of modern electrophysiological tools was employed to test for flash-activated ERC signals in cells stably expressing normal human rod opsin after regeneration with 11-cis-retinal. ERCs are similar in waveform and kinetics to those found in photoreceptors. The action spectrum of the major R(2) charge motion is consistent with a rhodopsin photopigment. The R(1) phase is not kinetically resolvable and the R(2) phase, which overlaps metarhodopsin-II formation, has a rapid risetime and complex multiexponential decay. These experiments demonstrate, for the first time, kinetically resolved electrical state transitions during activation of expressed visual pigment in a unicellular environment (single or fused giant cells) containing only 6 x 10(6)-8 x 10(7) molecules of rhodopsin. This method improves measurement sensitivity 7 to 8 orders of magnitude compared to other time-resolved techniques applied to rhodopsin to study the role particular amino acids play in conformational activation and the forces that govern those transitions. PMID:10465746
Light-induced exposure of the cytoplasmic end of transmembrane helix seven in rhodopsin

PubMed Central

Abdulaev, Najmoutin G.; Ridge, Kevin D.

1998-01-01

A key step in signal transduction in the visual cell is the light-induced conformational change of rhodopsin that triggers the binding and activation of the guanine nucleotide-binding protein. Site-directed mAbs against bovine rhodopsin were produced and used to detect and characterize these conformational changes upon light activation. Among several antibodies that bound exclusively to the light-activated state, an antibody (IgG subclass) with the highest affinity (Ka ≈ 6 × 10−9 M) was further purified and characterized. The epitope of this antibody was mapped to the amino acid sequence 304–311. This epitope extends from the central region to the cytoplasmic end of the seventh transmembrane helix and incorporates a part of a highly conserved NPXXY motif, a critical region for signaling and agonist-induced internalization of several biogenic amine and peptide receptors. In the dark state, no binding of the antibody to rhodopsin was detected. Accessibility of the epitope to the antibody correlated with formation of the metarhodopsin II photointermediate and was reduced significantly at the metarhodopsin III intermediate. Further, incubation of the antigen–antibody complex with 11-cis-retinal failed to regenerate the native rhodopsin chromophore. These results suggest significant and reversible conformational changes in close proximity to the cytoplasmic end of the seventh transmembrane helix of rhodopsin that might be important for folding and signaling. PMID:9789004
Ulex europaeus agglutinin II (UEA-II) is a novel, potent inhibitor of complement activation.

PubMed

Lekowski, R; Collard, C D; Reenstra, W R; Stahl, G L

2001-02-01

Complement is an important mediator of vascular injury following oxidative stress. We recently demonstrated that complement activation following endothelial oxidative stress is mediated by mannose-binding lectin (MBL) and activation of the lectin complement pathway. Here, we investigated whether nine plant lectins which have a binding profile similar to that of MBL competitively inhibit MBL deposition and subsequent complement activation following human umbilical vein endothelial cell (HUVEC) oxidative stress. HUVEC oxidative stress (1% O(2), 24 hr) significantly increased Ulex europaeus agglutinin II (UEA-II) binding by 72 +/- 9% compared to normoxic cells. UEA-II inhibited MBL binding to HUVEC in a concentration-dependent manner following oxidative stress. Further, MBL inhibited UEA-II binding to HUVEC in a concentration-dependent manner following oxidative stress, suggesting a common ligand. UEA-II (< or = 100 micromol/L) did not attenuate the hemolytic activity, nor did it inhibit C3a des Arg formation from alternative or classical complement pathway-specific hemolytic assays. C3 deposition (measured by ELISA) following HUVEC oxidative stress was inhibited by UEA-II in a concentration-dependent manner (IC(50) = 10 pmol/L). UEA-II inhibited C3 and MBL co-localization (confocal microscopy) in a concentration-dependent manner on HUVEC following oxidative stress (IC(50) approximately 1 pmol/L). Finally, UEA-II significantly inhibited complement-dependent neutrophil chemotaxis, but failed to inhibit fMLP-mediated chemotaxis, following endothelial oxidative stress. These data demonstrate that UEA-II is a novel, potent inhibitor of human MBL deposition and complement activation following human endothelial oxidative stress.
Ulex europaeus agglutinin II (UEA-II) is a novel, potent inhibitor of complement activation

PubMed Central

Lekowski, Robert; Collard, Charles D.; Reenstra, Wende R.; Stahl, Gregory L.

2001-01-01

Complement is an important mediator of vascular injury following oxidative stress. We recently demonstrated that complement activation following endothelial oxidative stress is mediated by mannose-binding lectin (MBL) and activation of the lectin complement pathway. Here, we investigated whether nine plant lectins which have a binding profile similar to that of MBL competitively inhibit MBL deposition and subsequent complement activation following human umbilical vein endothelial cell (HUVEC) oxidative stress. HUVEC oxidative stress (1% O2, 24 hr) significantly increased Ulex europaeus agglutinin II (UEA-II) binding by 72 ± 9% compared to normoxic cells. UEA-II inhibited MBL binding to HUVEC in a concentration-dependent manner following oxidative stress. Further, MBL inhibited UEA-II binding to HUVEC in a concentration-dependent manner following oxidative stress, suggesting a common ligand. UEA-II (≤ 100 μmol/L) did not attenuate the hemolytic activity, nor did it inhibit C3a des Arg formation from alternative or classical complement pathway-specific hemolytic assays. C3 deposition (measured by ELISA) following HUVEC oxidative stress was inhibited by UEA-II in a concentration-dependent manner (IC50 = 10 pmol/L). UEA-II inhibited C3 and MBL co-localization (confocal microscopy) in a concentration-dependent manner on HUVEC following oxidative stress (IC50 ≈ 1 pmol/L). Finally, UEA-II significantly inhibited complement-dependent neutrophil chemotaxis, but failed to inhibit fMLP-mediated chemotaxis, following endothelial oxidative stress. These data demonstrate that UEA-II is a novel, potent inhibitor of human MBL deposition and complement activation following human endothelial oxidative stress. PMID:11266613

Comparative study on kinetic adsorption of Cu(II), Cd(II) and Ni(II) ions from aqueous solutions using activated sludge and dried sludge

NASA Astrophysics Data System (ADS)

Ong, Soon-An; Toorisaka, Eiichi; Hirata, Makoto; Hano, Tadashi

2013-03-01

The adsorption of Cu(II), Cd(II) and Ni(II) ions from aqueous solutions by activated sludge and dried sludge was investigated under laboratory conditions to assess its potential in removing metal ions. The adsorption behavior of metal ions onto activated sludge and dried sludge was analyzed with Weber-Morris intra-particle diffusion model, Lagergren first-order model and pseudo second-order model. The rate constant of intra-particle diffusion on activated sludge and dried sludge increased in the sequence of Cu(II) > Ni(II) > Cd(II). According to the regression coefficients, it was observed that the kinetic adsorption data can fit better by the pseudo second-order model compared to the first-order Lagergren model with R 2 > 0.997. The adsorption capacities of metal ions onto activated sludge and dried sludge followed the sequence Ni(II) ≈ Cu(II) > Cd(II) and Cu(II) > Ni(II) > Cd(II).
Helix formation in arrestin accompanies recognition of photoactivated rhodopsin.

PubMed

Feuerstein, Sophie E; Pulvermüller, Alexander; Hartmann, Rudolf; Granzin, Joachim; Stoldt, Matthias; Henklein, Peter; Ernst, Oliver P; Heck, Martin; Willbold, Dieter; Koenig, Bernd W

2009-11-17

Binding of arrestin to photoactivated phosphorylated rhodopsin terminates the amplification of visual signals in photoreceptor cells. Currently, there is no crystal structure of a rhodopsin-arrestin complex available, although structures of unbound rhodopsin and arrestin have been determined. High-affinity receptor binding is dependent on distinct arrestin sites responsible for recognition of rhodopsin activation and phosphorylation. The loop connecting beta-strands V and VI in rod arrestin has been implicated in the recognition of active rhodopsin. We report the structure of receptor-bound arrestin peptide Arr(67-77) mimicking this loop based on solution NMR data. The peptide binds photoactivated rhodopsin in the unphosphorylated and phosphorylated form with similar affinities and stabilizes the metarhodopsin II photointermediate. A largely alpha-helical conformation of the receptor-bound peptide is observed.
Manganese-dependent carboanhydrase activity of photosystem II proteins.

PubMed

Shitov, A V; Pobeguts, O V; Smolova, T N; Allakhverdiev, S I; Klimov, V V

2009-05-01

Four sources of carbonic anhydrase (CA) activity in submembrane preparations of photosystem II (PS II) isolated from pea leaves were examined. Three of them belong to the hydrophilic proteins of the oxygen-evolving complex of PS II with molecular mass 33 kDa (protein PsbO), 24 kDa (protein PsbP), and 18 kDa (protein PsbQ). The fourth source of CA activity is associated with a pigment-protein complex of PS II after removing three hydrophilic proteins by salt treatment. Except for protein PsbQ, the CA activity of all these proteins depends on the presence of Mn2+: the purified protein PsbO did not show CA activity before adding Mn2+ into the medium (concentration of Mn2+ required for 50% effect, EC(50), was 670 microM); CA activity of protein mixture composed of PsbP and PsbQ increased more than 5-fold upon adding Mn2+ (EC(50) was 45 microM). CA activity of purified protein PsbP increased 2-fold in the presence of 200 microM Mn2+. As indicated for the mixture of two proteins (PsbP and PsbQ), Mg2+, Ca2+, and Zn2+, in contrast to Mn2+, suppressed CA activity (both initial and Mn2+-induced activity). Since the found sources of CA activity demonstrated properties different from ones of typical CA (need for Mn2+, insensitivity or low sensitivity to acetazolamide or ethoxyzolamide) and such CA activity was found only among PS II proteins, we cannot exclude that they belong to the type of Mn-dependent CA associated with PS II.
Zn(II) stimulation of Fe(II)-activated repression in the iron-dependent repressor from Mycobacterium tuberculosis.

PubMed

Stapleton, Brian; Walker, Lawrence R; Logan, Timothy M

2013-03-19

Thermodynamic measurements of Fe(II) binding and activation of repressor function in the iron-dependent repressor from Mycobacterium tuberculosis (IdeR) are reported. IdeR, a member of the diphtheria toxin repressor family of proteins, regulates iron homeostasis and contributes to the virulence response in M. tuberculosis. Although iron is the physiological ligand, this is the first detailed analysis of iron binding and activation in this protein. The results showed that IdeR binds 2 equiv of Fe(II) with dissociation constants that differ by a factor of 25. The high- and low-affinity iron binding sites were assigned to physical binding sites I and II, respectively, using metal binding site mutants. IdeR was also found to contain a high-affinity Zn(II) binding site that was assigned to physical metal binding site II through the use of binding site mutants and metal competition assays. Fe(II) binding was modestly weaker in the presence of Zn(II), but the coupled metal binding-DNA binding affinity was significantly stronger, requiring 30-fold less Fe(II) to activate DNA binding compared to Fe(II) alone. Together, these results suggest that IdeR is a mixed-metal repressor, where Zn(II) acts as a structural metal and Fe(II) acts to trigger the physiologically relevant promoter binding. This new model for IdeR activation provides a better understanding of IdeR and the biology of iron homeostasis in M. tuberculosis.
World War II Memorial Learning Activities.

ERIC Educational Resources Information Center

Tennessee State Dept. of Education, Nashville.

These learning activities can help students get the most out of a visit to the Tennessee World War II Memorial, a group of ten pylons located in Nashville (Tennessee). Each pylon contains informational text about the events of World War II. The ten pylons are listed as: (1) "Pylon E-1--Terror: America Enters the War against Fascism, June…
Fe (III), Co(II), Ni(II), Cu(II) and Zn(II) complexes of schiff bases based-on glycine and phenylalanine: Synthesis, magnetic/thermal properties and antimicrobial activity

NASA Astrophysics Data System (ADS)

Sevgi, Fatih; Bagkesici, Ugur; Kursunlu, Ahmed Nuri; Guler, Ersin

2018-02-01

Zinc (II), copper (II), nickel (II), cobalt (II) and iron (III) complexes of Schiff bases (LG, LP) derived from 2-hydroxynaphthaldehyde with glycine and phenylalanine were reported and characterized by 1H NMR, 13C NMR, elemental analyses, melting point, FT-IR, magnetic susceptibility and thermal analyses (TGA). TGA data show that iron and cobalt include to the coordinated water and metal:ligand ratio is 1:2 while the complex stoichiometry for Ni (II), Cu (II) and Zn (II) complexes is 1:1. As expected, Ni (II) and Zn (II) complexes are diamagnetic; Cu (II), Co (II) and Fe (III) complexes are paramagnetic character due to a strong ligand of LG and LP. The LG, LP and their metal complexes were screened for their antimicrobial activities against five Gram-positive (Staphylococcus aureus, Methicillin resistant Staphylococcus aureus (MRSA), Bacillus cereus, Streptococcus mutans and Enterococcus faecalis) and three Gram-negative (Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa) and one fungi (Candida albicans) by using broth microdilution techniques. The activity data show that ligands and their metal complexes exhibited moderate to good activity against Gram-positive bacteria and fungi.
Catalase-like activity studies of the manganese(II) adsorbed zeolites

NASA Astrophysics Data System (ADS)

ćiçek, Ekrem; Dede, Bülent

2013-12-01

Preparation of manganese(II) adsorbed on zeolite 3A, 4A, 5A. AW-300, ammonium Y zeolite, organophilic, molecular sieve and catalase-like enzyme activity of manganese(II) adsorbed zeolites are reported herein. Firstly zeolites are activated at 873 K for two hours before contact manganese(II) ions. In order to observe amount of adsorption, filtration process applied for the solution. The pure zeolites and manganese(II) adsorbed zeolites were analysed by FT-IR. As a result according to the FT-IR spectra, the incorporation of manganese(II) cation into the zeolite structure causes changes in the spectra. These changes are expected particularly in the pseudolattice bands connected with the presence of alumino and silicooxygen tetrahedral rings in the zeolite structure. Furthermore, the catalytic activities of the Mn(II) adsorbed zeolites for the disproportionation of hydrogen peroxide were investigated in the presence of imidazole. The Mn(II) adsorbed zeolites display efficiency in the disproportion reactions of hydrogen peroxide, producing water and dioxygen in catalase-like activity.
Synthesis, spectroscopic characterization and biological activities of N4O2 Schiff base ligand and its metal complexes of Co(II), Ni(II), Cu(II) and Zn(II)

NASA Astrophysics Data System (ADS)

Al-Resayes, Saud I.; Shakir, Mohammad; Abbasi, Ambreen; Amin, Kr. Mohammad Yusuf; Lateef, Abdul

The Schiff base ligand, bis(indoline-2-one)triethylenetetramine (L) obtained from condensation of triethylenetetramine and isatin was used to synthesize the complexes of type, [ML]Cl2 [M = Co(II), Ni(II), Cu(II) and Zn(II)]. L was characterized on the basis of the results of elemental analysis, FT-IR, 1H and 13C NMR, mass spectroscopic studies. The stoichiometry, bonding and stereochemistries of complexes were ascertained on the basis of results of elemental analysis, magnetic susceptibility values, molar conductance and various spectroscopic studies. EPR, UV-vis and magnetic moments revealed an octahedral geometry for complexes. L and its Cu(II) and Zn(II) complexes were screened for their antibacterial activity. Analgesic activity of Cu(II) and Zn(II) complexes was also tested in rats by tail flick method. Both complexes were found to possess good antibacterial and moderate analgesic activity.
Anticancer, antibacterial and antifungal activity of new ni (ii) and cu (ii) complexes of imidazole-phenanthroline derivatives.

PubMed

Moghadam, Mahboube Eslami; Divsalar, Adeleh; Zare, Marziye Shahraki; Gholizadeh, Roghayeh; Mahalleh, Doran; Saghatforosh, Lotfali; Sanati, Soheila

2017-11-02

Two new nickel(II) and copper(II) complexes of 2-(Furan-2-yl)-1H-Imidazo[4,5-f][1,10]Phenanthroline (FIP) and 2-(thiophen-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (TIP), imidazophen derivatives were synthesized. The structures of the compounds were determined by UV-visible and FT-IR spectroscopic methods and elemental analysis. The biological activities of Ni and Cu complexes, as anticancer agents, were tested against chronic myelogenous leukemia cell line, K562, at micromolar concentration. The MTT studies showed Cc 50 values are 21 and 160 µM for Cu and Ni(II) complexes, respectively; suggesting that Ni (II) complex has Cc 50 almost seven times of that obtained for cisplatin. Biological activity of the Ni(II) and Cu(II) complexes were also assayed against selective microorganisms by disc diffusion method. These results showed that the Cu(II) complex is antifungal agent but Ni(II) complex has antibacterial activity.
Angiotensin II regulation of neuromodulation: downstream signaling mechanism from activation of mitogen-activated protein kinase.

PubMed

Lu, D; Yang, H; Raizada, M K

1996-12-01

Angiotensin II (Ang II) stimulates expression of tyrosine hydroxylase and norepinephrine transporter genes in brain neurons; however, the signal-transduction mechanism is not clearly defined. This study was conducted to determine the involvement of the mitogen-activated protein (MAP) kinase signaling pathway in Ang II stimulation of these genes. MAP kinase was localized in the perinuclear region of the neuronal soma. Ang II caused activation of MAP kinase and its subsequent translocation from the cytoplasmic to nuclear compartment, both effects being mediated by AT1 receptor subtype. Ang II also stimulated SRE- and AP1-binding activities and fos gene expression and its translocation in a MAP kinase-dependent process. These observations are the first demonstration of a downstream signaling pathway involving MAP kinase in Ang II-mediated neuromodulation in noradrenergic neurons.
Synthesis, Characterization and Antibacterial Activity of 1,4-di[ aminomethylene carboxyl] phenylene (H2L) and its Complexes Co(II), Cu (II), Zn(II) and Cd (II)

NASA Astrophysics Data System (ADS)

Sultan, J. S.; Fezea, S. M.; Mousa, F. H.

2018-05-01

A binucleating tetradentate Schiff base ligand, 1,4- di[amino methylene carboxylic] phenylene (H2L) and its forth new binuclear complexes [Co(II), Cu(II), Zn(II) and Cd(II)] were prepared via reaction metal (II) chloride with ligand (H2L) using 2:1 (M:L) in ethanol solvent. The new ligand (H2L) and its complexes were characterized by elemental microanalysis (C.H.N), atomic absorption, chloride content, molar conductance’s magnetic susceptibility, FTIR UV- Vis spectral and, 1H, 13 C- NMR (for H2L). The antibacterial activity with bacteria activity with bacteria, Staphylococcus aureus, Bacillus and Esccherichia Coli were studied.
Rapid hydrogen ion uptake of rod outer segments and rhodopsin solutions on illumination

PubMed Central

Falk, G.; Fatt, P.

1966-01-01

1. Flash illumination of a suspension of frog rod outer segments or rhodopsin solution in contact with a platinum electrode produces a rapidly developing negative displacement of potential of the electrode (with respect to a reversible electrode). 2. The amplitude of the potential change varies inversely with the H+ buffering capacity of the medium. It is inferred that the response is due to an uptake of H+ by the rod outer segments or rhodopsin, with the platinum surface acting as a pH electrode. 3. Determination of the action spectrum shows that the response depends on the absorption of light by rhodopsin. 4. In frog rods one acid-binding group with a pK of about 7·9 is produced for each molecule of rhodopsin bleached, consistent with a rhodopsin concentration in frog rods of 1·7 mM. 5. It is suggested that the time course of the response with rhodopsin solutions reflects the kinetics of the conversion of metarhodopsin I to metarhodopsin II. 6. A slower time course of voltage change observed for suspensions of outer segments is attributable to the time required for the diffusion of H+ buffer out of the rods. PMID:5945249
Stellar activity with LAMOST - II. Chromospheric activity in open clusters

NASA Astrophysics Data System (ADS)

Fang, Xiang-Song; Zhao, Gang; Zhao, Jing-Kun; Bharat Kumar, Yerra

2018-05-01

We use the LAMOST spectra of member stars in Pleiades, M34, Praesepe, and Hyades to study how chromospheric activity varies as a function of mass and rotation at different age. We measured excess equivalent widths of H α, H β, and Ca II K based on estimated chromospheric contributions from old and inactive field dwarfs, and excess luminosities are obtained by normalizing bolometric luminosity, for more than 700 late-type stars in these open clusters. Results indicate two activity sequences in cool spot coverage and H α excess emission among GK dwarfs in Pleiades and M dwarfs in Praesepe and Hyades, paralleling with well-known rotation sequences. A weak dependence of chromospheric emission on rotation exists among ultrafast rotators in saturated regime with Rossby number Ro ≲ 0.1. In the unsaturated regime, chromospheric and coronal emission show similar dependence on Ro, but with a shift towards larger Ro, indicating chromospheric emission gets easily saturated than coronal emission, and/or convective turnover time-scales based on X-ray data do not work well with chromospheric emission. More interestingly, our analysis shows fully convective slow rotators obey the rotation-chromospheric activity relation similar to hotter stars, confirming the previous finding. We found correlations among H α, H β, and Ca II K emissions, in which H α losses are more important than Ca II K for cooler and more active stars. In addition, a weak correlation is seen between chromospheric emission and photospheric activity that shows dependence on stellar spectral type and activity level, which provides some clues on how spot configuration varies as a function of mass and activity level.
Angiotensin II stimulates calcium-dependent activation of c-Jun N-terminal kinase.

PubMed Central

Zohn, I E; Yu, H; Li, X; Cox, A D; Earp, H S

1995-01-01

In GN4 rat liver epithelial cells, angiotensin II (Ang II) and other agonists which activate phospholipase C stimulate tyrosine kinase activity in a calcium-dependent, protein kinase C (PKC)-independent manner. Since Ang II also produces a proliferative response in these cells, we investigated downstream signaling elements traditionally linked to growth control by tyrosine kinases. First, Ang II, like epidermal growth factor (EGF), stimulated AP-1 binding activity in a PKC-independent manner. Because increases in AP-1 can reflect induction of c-Jun and c-Fos, we examined the activity of the mitogen-activated protein (MAP) kinase family members Erk-1 and -2 and the c-Jun N-terminal kinase (JNK), which are known to influence c-Jun and c-Fos transcription. Ang II stimulated MAP kinase (MAPK) activity but only approximately 50% as effectively as EGF; again, these effects were independent of PKC. Ang II also produced a 50- to 200-fold activation of JNK in a PKC-independent manner. Unlike its smaller effect on MAPK, Ang II was approximately four- to sixfold more potent in activating JNK than EGF was. Although others had reported a lack of calcium ionophore-stimulated JNK activity in lymphocytes and several other cell lines, we examined the role of calcium in GN4 cells. The following results suggest that JNK activation in rat liver epithelial cells is at least partially Ca(2+) dependent: (i) norepinephrine and vasopressin hormones that increase inositol 1,4,5-triphosphate stimulated JNK; (ii) both thapsigargin, a compound that produces an intracellular Ca(2+) signal, and Ca(2+) ionophores stimulated a dramatic increase in JNK activity (up to 200-fold); (iii) extracellular Ca(2+) chelation with ethylene glycol tetraacetic acid (EGTA) inhibited JNK activation by ionophore and intracellular chelation with 1,2-bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl-ester (BAPTA-AM) partially inhibited JNK activation by Ang II or thapsigargin; and (iv) JNK
Electrochemical studies of DNA interaction and antimicrobial activities of MnII, FeIII, CoII and NiII Schiff base tetraazamacrocyclic complexes

NASA Astrophysics Data System (ADS)

Kumar, Anuj; Vashistha, Vinod Kumar; Tevatia, Prashant; Singh, Randhir

2017-04-01

Tetraazamacrocyclic complexes of MnII, FeIII, CoII and NiII have been synthesized by template method. These tetraazamacrocycles have been analyzed with various techniques like molar conductance, IR, UV-vis, mass spectral and cyclic voltammetric studies. On the basis of all these studies, octahedral geometry has been assigned to these tetraazamacrocyclic complexes. The DNA binding properties of these macrocyclic complexes have been investigated by electronic absorption spectra, fluorescence spectra, cyclic voltammetric and differential pulse voltammetric studies. The cyclic voltammetric data showed that ipc and ipa were effectively decreased in the presence of calf thymus DNA, which is a strong evidence for the interaction of these macrocyclic complexes with the calf thymus DNA (ct-DNA). The heterogeneous electron transfer rate constant found in the order: KCoII > KNiII > KMnII which indicates that CoII macrocyclic complex has formed a strong intercalated intermediate. The Stern-Volmer quenching constant (KSV) and voltammetric binding constant were found in the order KSV(CoII) > KSV(NiII) > KSV(MnII) and K+(CoII) > K+(NiII) > K+(MnII) which shows that CoII macrocyclic complex exhibits the high interaction affinity towards ct-DNA by the intercalation binding. Biological studies of the macrocyclic complexes compared with the standard drug like Gentamycin, have shown antibacterial activities against E. coli, P. aeruginosa, B. cereus, S. aureus and antifungal activity against C. albicans.
Angiotensin II enhances norepinephrine spillover during sympathetic activation in conscious rabbits.

PubMed

Noshiro, T; Shimizu, K; Way, D; Miura, Y; McGrath, B P

1994-05-01

To investigate the potential modulating influence of angiotensin II (ANG II) on sympathetic activity in response to changes in baroreflex activity, renal and total norepinephrine (NE) spillover rates were examined during sodium nitroprusside (SNP) and phenylephrine (PE) infusions in four groups of conscious rabbits: 1) saline (control); 2) subpressor ANG II (ANG II, 2 ng.kg-1.min-1); 3) enalaprilat (MK-422, 200 micrograms/kg and 3.3 micrograms.kg-1.min-1); and 4) MK plus ANG II (MK+ANG II). Upper plateaus of baroreflex-NE spillover curves for renal and total NE spillover were reduced in the MK group (25 and 81 ng/min) compared with control (38 and 125 ng/min) and MK+ANG II (37 and 155 ng/min). To investigate the interaction of ANG II and sympathetic activity during treadmill exercise, hindlimb NE spillover rate was examined in three groups of rabbits: 1) control, 2) MK, and 3) MK+ANG II. Exercise at 6 and 12 m/min produced similar effort-related hemodynamic responses in the three groups. At maximal exercise, hindlimb NE spillover was reduced in the MK group (29 +/- 3 ng/min) compared with control (62 +/- 17 ng/min, P < 0.05) and MK+ANG II group (51 +/- 10 ng/min). It is concluded that endogenous ANG II enhances sympathetic activity during pharmacological (baroreflex) and physiological stimulation.
Angiotensin II and angiotensin II receptor blocker modulate the arrhythmogenic activity of pulmonary veins.

PubMed

Chen, Yi-Jen; Chen, Yao-Chang; Tai, Ching-Tai; Yeh, Hung-I; Lin, Cheng-I; Chen, Shih-Ann

2006-01-01

Angiotensin II receptor blockers (AIIRBs) have been shown to prevent atrial fibrillation. The pulmonary veins (PVs) are the most important focus for the generation of atrial fibrillation. The aim of this study was to evaluate whether angiotensin II or AIIRB may change the arrhythmogenic activity of the PVs. Conventional microelectrodes and whole-cell patch clamps were used to investigate the action potentials (APs) and ionic currents in isolated rabbit PV tissue and single cardiomyocytes before and after administering angiotensin II or losartan (AIIRB). In the tissue preparations, angiotensin II induced delayed after-depolarizations (1, 10, and 100 nM) and accelerated the automatic rhythm (10 and 100 nM). Angiotensin II (100 nM) prolonged the AP duration and increased the contractile force (10 and 100 nM). Losartan (1 and 10 microM) inhibited the automatic rhythm. Losartan (10 microM) prolonged the AP duration and reduced the contractile force (1 and 10 microM). Angiotensin II reduced the transient outward potassium current (I(to)) but increased the L-type calcium, delayed rectifier potassium (I(K)), transient inward (I(ti)), pacemaker, and Na(+)-Ca(2+) exchanger (NCX) currents in the PV cardiomyocytes. Losartan decreased the I(to), I(K), I(ti), and NCX currents. In conclusion, angiotensin II and AIIRB modulate the PV electrical activity, which may play a role in the pathophysiology of atrial fibrillation.
Activation of peroxisome proliferator-activated receptor δ inhibits angiotensin II-induced activation of matrix metalloproteinase-2 in vascular smooth muscle cells.

PubMed

Ham, Sun Ah; Lee, Hanna; Hwang, Jung Seok; Kang, Eun Sil; Yoo, Taesik; Paek, Kyung Shin; Do, Jeong Tae; Park, Chankyu; Oh, Jae-Wook; Kim, Jin-Hoi; Han, Chang Woo; Seo, Han Geuk

2014-01-01

We investigated the role of peroxisome proliferator-activated receptor (PPAR) δ on angiotensin (Ang) II-induced activation of matrix metalloproteinase (MMP)-2 in vascular smooth muscle cells (VSMCs). Activation of PPARδ by GW501516, a specific ligand for PPARδ, attenuated Ang II-induced activation of MMP-2 in a concentration-dependent manner. GW501516 also inhibited the generation of reactive oxygen species in VSMCs treated with Ang II. A marked increase in the mRNA levels of tissue inhibitor of metalloproteinase (TIMP)-2 and -3, endogenous antagonists of MMPs, was also observed in GW501516-treated VSMCs. These effects were markedly reduced in the presence of siRNAs against PPARδ, indicating that the effects of GW501516 are PPARδ dependent. Among the protein kinases inhibited by GW501516, suppression of phosphatidylinositol 3-kinase/Akt signaling was shown to have the greatest effect on activation of MMP-2 in VSMCs treated with Ang II. Concomitantly, GW501516-mediated inhibition of MMP-2 activation in VSMCs treated with Ang II was associated with the suppression of cell migration to levels approaching those in cells not exposed to Ang II. Thus, activation of PPARδ confers resistance to Ang II-induced degradation of the extracellular matrix by upregulating expression of its endogenous inhibitor TIMP and thereby modulating cellular responses to Ang II in vascular cells. © 2014 S. Karger AG, Basel.
Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, Rui-Qing; Tang, Xiao-Feng; Zhang, Bao-Li

Adventitial fibroblasts (AFs) can be activated by angiotensin II (Ang II) and exert pro-fibrotic and pro-inflammatory effects in vascular remodeling. Protease-activated receptor (PAR) 1 and 2 play a significant role in fibrogenic and inflammatory diseases. The present study hypothesized that PAR1 and PAR2 are involved in Ang II-induced AF activation and contribute to adventitial remodeling. We found that direct activation of PAR1 and PAR2 with PAR1-AP and PAR2-AP led to AF activation, including proliferation and differentiation of AFs, extracellular matrix synthesis, as well as production of pro-fibrotic cytokine TGF-β and pro-inflammatory cytokines IL-6 and MCP-1. Furthermore, PAR1 and PAR2 mediatedmore » Ang II-induced AF activation, since both PAR1 and PAR2 antagonists inhibited Ang II-induced proliferation, migration, differentiation, extracellular matrix synthesis and production of pro-fibrotic and pro-inflammatory cytokines in AFs. Finally, mechanistic study showed that Ang II, via Ang II type I receptor (AT1R), upregulated both PAR1 and PAR2 expression, and transactivated PAR1 and PAR2, as denoted by internalization of both proteins. In conclusion, our results suggest that PAR1 and PAR2 play a critical role in Ang II-induced AF activation, and this may contribute to adventitia-related pathological changes. - Highlights: • Direct activation of PAR1 and PAR2 led to adventitial fibroblast (AF) activation. • PAR1 and PAR2 antagonists attenuated Ang II-induced AF activation. • Ang II induced the upregulation and transactivation of PAR1/PAR2 in AFs.« less
Visual pigment spectra of the comma butterfly, Polygonia c-album, derived from in vivo epi-illumination microspectrophotometry.

PubMed

Vanhoutte, Kurt J A; Stavenga, Doekele G

2005-05-01

The visual pigments in the compound eye of the comma butterfly, Polygonia c-album, were investigated in a specially designed epi-illumination microspectrophotometer. Absorption changes due to photochemical conversions of the visual pigments, or due to light-independent visual pigment decay and regeneration, were studied by measuring the eye shine, i.e., the light reflected from the tapetum located in each ommatidium proximal to the visual pigment-bearing rhabdom. The obtained absorbance difference spectra demonstrated the dominant presence of a green visual pigment. The rhodopsin and its metarhodopsin have absorption peak wavelengths at 532 nm and 492 nm, respectively. The metarhodopsin is removed from the rhabdom with a time constant of 15 min and the rhodopsin is regenerated with a time constant of 59 min (room temperature). A UV rhodopsin with metarhodopsin absorbing maximally at 467 nm was revealed, and evidence for a blue rhodopsin was obtained indirectly.

Estrogen Modulation of MgATPase Activity of Nonmuscle Myosin-II-B Filaments

PubMed Central

Gorodeski, George I.

2008-01-01

The study tested the hypothesis that estrogen controls epithelial paracellular resistance through modulation of myosin. The objective was to understand how estrogen modulates non-muscle myosin-II-B (NMM-II-B), the main component of the cortical actomyosin in human epithelial cervical cells. Experiments used human cervical epithelial cells CaSki as a model, and end points were NMM-II-B phosphorylation, filamentation, and MgATPase activity. The results were as follows: 1) treatment with estrogen increased phosphorylation and MgATPase activity and decreased NMM-II-B filamentation; 2) estrogen effects could be blocked by antisense nucleotides for the estrogen receptor-α and by ICI-182,780, tamoxifen, and the casein kinase-II (CK2) inhibitor, 5,6-dichloro-1-β-(D)-ribofuranosylbenzimidazole and attenuated by AG1478 and PD98059 (inhibitors of epithelial growth factor receptor and ERK/MAPK) but not staurosporine [blocker of protein kinase C (PKC)]; 3) treatments with the PKC activator sn-1,2-di-octanoyl diglyceride induced biphasic effect on NMM-II-B MgATPase activity: an increase at 1 nM to 1 μM and a decrease in activity at more than 1 μM; 4) sn-1,2-dioctanoyl diglyceride also decreased NMM-II-B filamentation in a monophasic and saturable dose dependence (EC50 1–10 μM); 5) when coincubated directly with purified NMM-II-B filaments, both CK2 and PKC decreased filamentation and increased MgATPase activity; 6) assays done on disassembled NMM-II-B filaments showed MgATPase activity in filaments obtained from estrogen-treated cells but not estrogen-depleted cells; and 7) incubations in vitro with CK2, but not PKC, facilitated MgATPase activity, even in disassembled NMM-II-B filaments. The results suggest that estrogen, in an effect mediated by estrogen receptor-α and CK2 and involving the epithelial growth factor receptor and ERK/MAPK cascades, increases NMM-II-B MgATPase activity independent of NMM-II-B filamentation status. PMID:17023528
Endothelial-monocyte activating polypeptide II disrupts alveolar epithelial type II to type I cell transdifferentiation

PubMed Central

2012-01-01

Background Distal alveolar morphogenesis is marked by differentiation of alveolar type (AT)-II to AT-I cells that give rise to the primary site of gas exchange, the alveolar/vascular interface. Endothelial-Monocyte Activating Polypeptide (EMAP) II, an endogenous protein with anti-angiogenic properties, profoundly disrupts distal lung neovascularization and alveolar formation during lung morphogenesis, and is robustly expressed in the dysplastic alveolar regions of infants with Bronchopulmonary dysplasia. Determination as to whether EMAP II has a direct or indirect affect on ATII→ATI trans-differentiation has not been explored. Method In a controlled nonvascular environment, an in vitro model of ATII→ATI cell trans-differentiation was utilized to demonstrate the contribution that one vascular mediator has on distal epithelial cell differentiation. Results Here, we show that EMAP II significantly blocked ATII→ATI cell transdifferentiation by increasing cellular apoptosis and inhibiting expression of ATI markers. Moreover, EMAP II-treated ATII cells displayed myofibroblast characteristics, including elevated cellular proliferation, increased actin cytoskeleton stress fibers and Rho-GTPase activity, and increased nuclear:cytoplasmic volume. However, EMAP II-treated cells did not express the myofibroblast markers desmin or αSMA. Conclusion Our findings demonstrate that EMAP II interferes with ATII → ATI transdifferentiation resulting in a proliferating non-myofibroblast cell. These data identify the transdifferentiating alveolar cell as a possible target for EMAP II's induction of alveolar dysplasia. PMID:22214516
Formation and Decay of the Arrestin·Rhodopsin Complex in Native Disc Membranes*

PubMed Central

Beyrière, Florent; Sommer, Martha E.; Szczepek, Michal; Bartl, Franz J.; Hofmann, Klaus Peter; Heck, Martin; Ritter, Eglof

2015-01-01

In the G protein-coupled receptor rhodopsin, light-induced cis/trans isomerization of the retinal ligand triggers a series of distinct receptor states culminating in the active Metarhodopsin II (Meta II) state, which binds and activates the G protein transducin (Gt). Long before Meta II decays into the aporeceptor opsin and free all-trans-retinal, its signaling is quenched by receptor phosphorylation and binding of the protein arrestin-1, which blocks further access of Gt to Meta II. Although recent crystal structures of arrestin indicate how it might look in a precomplex with the phosphorylated receptor, the transition into the high affinity complex is not understood. Here we applied Fourier transform infrared spectroscopy to monitor the interaction of arrestin-1 and phosphorylated rhodopsin in native disc membranes. By isolating the unique infrared signature of arrestin binding, we directly observed the structural alterations in both reaction partners. In the high affinity complex, rhodopsin adopts a structure similar to Gt-bound Meta II. In arrestin, a modest loss of β-sheet structure indicates an increase in flexibility but is inconsistent with a large scale structural change. During Meta II decay, the arrestin-rhodopsin stoichiometry shifts from 1:1 to 1:2. Arrestin stabilizes half of the receptor population in a specific Meta II protein conformation, whereas the other half decays to inactive opsin. Altogether these results illustrate the distinct binding modes used by arrestin to interact with different functional forms of the receptor. PMID:25847250
Trimethoprim degradation by Fenton and Fe(II)-activated persulfate processes.

PubMed

Wang, Shizong; Wang, Jianlong

2018-01-01

Trimethoprim is a pollutant ubiquitous in the environment due to its extensive application, and it cannot be effectively removed by conventional wastewater treatment processes. In this study, the Fenton and the Fe(II)-activated persulfate processes were employed to degrade trimethoprim in an aqueous solution. The results showed that the concentration of persulfate, H 2 O 2 and Fe(II) a had significant influence on the degradation of trimethoprim in both processes. De-ionized water spiked with trimethoprim resulted in the complete degradation of trimethoprim (0.05 mM) by the mineralization of 54.9% of Fenton's reagent when the concentrations of H 2 O 2 and Fe(II) were 1 mM and 0.05 mM, respectively. In contrast, 73.4% of trimethoprim was degraded by the mineralization of 40.5% of the Fe(II)-activated persulfate process when the concentration of persulfate and Fe(II) were each 4 mM. Intermediate compounds with different m/z were detected for the Fenton and the Fe(II)-activated persulfate processes, indicating alternative degradation pathways. In the actual wastewater spiked with trimethoprim, the removal efficiency of trimethoprim decreased to 35.8% and 43.6%, respectively, for the Fenton and the Fe(II)-activated persulfate processes. In addition, the decomposition efficiencies for hydrogen peroxide and persulfate were 43.8% and 92.5%, respectively, which was lower than those in the de-ionized water system. These results demonstrated that wastewater components had a negative influence on trimethoprim degradation and the decomposition of the oxidants (persulfate and H 2 O 2 ). In summary, the Fe(II)-activated persulfate process could be used as an alternative technology for treating trimethoprim-containing wastewater. Copyright © 2017 Elsevier Ltd. All rights reserved.
Cadmium(II) and lead(II) adsorption onto hetero-atom functional mesoporous silica and activated carbon

NASA Astrophysics Data System (ADS)

Machida, Motoi; Fotoohi, Babak; Amamo, Yoshimasa; Mercier, Louis

2012-07-01

Adsorption of cadmium(II) and lead(II) on amino-, mercapto-functionalized mesoporous silica (HMS) and carboxylic-functionalized activated carbon (AC) were examined. The resultant isotherms fitted the Langmuir model and amino-functionalized HMS exhibited the highest adsorption capacity for both cadmium(II) and lead(II). Adsorption affinities for cadmium(II) were always greater than those for lead(II) in all three adsorbent types, while the difference between the two values was the largest for mercapto-functionalized HMS indicating a selective adsorption of cadmium(II). Influence of equilibrium solution pH on adsorption of cadmium(II), lead(II) and their binary mixtures was also studied. Carboxylic-functionalized AC adsorbed cadmium(II) and lead(II) in a wide pH range than conditions for the mercapto-functionalized HMS. It was concluded that each functional group had its own characteristics and advantages for adsorption of heavy metal ions; amino-groups showed high adsorption capacity, while mercapto-groups had good selectivity toward cadmium(II) adsorption and a wide solution pH in adsorption by carboxylic-groups were established in this study.
A Combined MG II/CA II Survey of Stellar Magnetic Activity in the Solar Neighborhood

NASA Technical Reports Server (NTRS)

Wicklund, B. M.; Donahue, R. A.; Dobson, A. K.; Baliunas, Sallie L.

1997-01-01

We use nearly contemporaneus low-resolution IUE observations of Mg II h + k emission and Mount Wilson Observatory Ca II H + K S indices for 33 pairs of observations of lower main sequence stars to formulate a relationship that will permit accurate predictions of S values as a function of (B - V) color and Mg II h + k flux. The resulting relationship is useful because it will extend the set of solar neighborhood stars for which a uniform estimate of chromospheric activity is available to include stars that are not observable from Mount Wilson as well as providing additional estimates of activity levels for stars that are on the Mount Wilson HK Project observing list.
Activation of calcineurin in human failing heart ventricle by endothelin-1, angiotensin II and urotensin II

PubMed Central

Li, Joan; Wang, Jianchun; Russell, Fraser D; Molenaar, Peter

2005-01-01

The calcineurin (CaN) enzyme–transcriptional pathway is critically involved in hypertrophy of heart muscle in some animal models. Currently there is no information concerning the regulation of CaN activation by endogenous agonists in human heart. Human right ventricular trabeculae from explanted human (14 male/2 female) failing hearts were set up in a tissue bath and electrically paced at 1 Hz and incubated with or without 100 nM endothelin-1 (ET-1), 10 μM, angiotensin-II (Ang II) or 20 nM human urotensin-II (hUII) for 30 min. Tissues from four patients were incubated with 200 nM tacrolimus (FK506) for 30 min and then incubated in the presence or absence of ET-1 for a further 30 min. ET-1 increased contractile force in all 13 patients (P<0.001). Ang II and hUII increased contractile force in three out of eight and four out of 10 patients but overall nonsignificantly (P>0.1). FK506 had no effect on contractile force (P=0.12). ET-1, Ang II and hUII increased calcineurin activity by 32, 71 and 15%, respectively, while FK506 reduced activity by 34%. ET-1 in the presence of FK506 did not restore calcineurin activity (P=0.1). There was no relationship between basal CaN activity and expression levels in the right ventricle. Increased levels of free phosphate were detected in ventricular homogenates that were incubated with PKCɛ compared to samples incubated without PKCɛ. Endogenous cardiostimulants which activate Gαq-coupled receptors increase the activity of calcineurin in human heart following acute (30 min) exposure. PKC may contribute to this effect by increasing levels of phosphorylated calcineurin substrate. PMID:15821752
Coordination behavior of tetraaza [N4] ligand towards Co(II), Ni(II), Cu(II), Cu(I) and Pd(II) complexes: Synthesis, spectroscopic characterization and anticancer activity

NASA Astrophysics Data System (ADS)

El-Boraey, Hanaa A.

2012-11-01

Novel eight Co(II), Ni(II), Cu(II), Cu(I) and Pd(II) complexes with [N4] ligand (L) i.e. 2-amino-N-{2-[(2-aminobenzoyl)amino]ethyl}benzamide have been synthesized and structurally characterized by elemental analysis, spectral, thermal (TG/DTG), magnetic, and molar conductivity measurements. On the basis of IR, mass, electronic and EPR spectral studies an octahedral geometry has been proposed for Co(II), Ni(II) complexes and Cu(II) chloride complex, square-pyramidal for Cu(I) bromide complex. For Cu(II) nitrate complex (6), Pd(II) complex (8) square planar geometry was proposed. The EPR data of Cu(II) complexes in powdered form indicate dx2-y2 ground state of Cu(II) ion. The antitumor activity of the synthesized ligand and some selected metal complexes has been studied. The palladium(II) complex (8) was found to display cytotoxicity (IC50 = 25.6 and 41 μM) against human breast cancer cell line MCF-7 and human hepatocarcinoma HEPG2 cell line.
Active-site solvent replenishment observed during human carbonic anhydrase II catalysis.

PubMed

Kim, Jin Kyun; Lomelino, Carrie L; Avvaru, Balendu Sankara; Mahon, Brian P; McKenna, Robert; Park, SangYoun; Kim, Chae Un

2018-01-01

Human carbonic anhydrase II (hCA II) is a zinc metalloenzyme that catalyzes the reversible hydration/dehydration of CO 2 /HCO 3 - . Although hCA II has been extensively studied to investigate the proton-transfer process that occurs in the active site, its underlying mechanism is still not fully understood. Here, ultrahigh-resolution crystallographic structures of hCA II cryocooled under CO 2 pressures of 7.0 and 2.5 atm are presented. The structures reveal new intermediate solvent states of hCA II that provide crystallographic snapshots during the restoration of the proton-transfer water network in the active site. Specifically, a new intermediate water (W I ') is observed next to the previously observed intermediate water W I , and they are both stabilized by the five water molecules at the entrance to the active site (the entrance conduit). Based on these structures, a water network-restructuring mechanism is proposed, which takes place at the active site after the nucleophilic attack of OH - on CO 2 . This mechanism explains how the zinc-bound water (W Zn ) and W1 are replenished, which are directly responsible for the reconnection of the His64-mediated proton-transfer water network. This study provides the first 'physical' glimpse of how a water reservoir flows into the hCA II active site during its catalytic activity.
Retinal Ligand Mobility Explains Internal Hydration and Reconciles Active Rhodopsin Structures

PubMed Central

Leioatts, Nicholas; Mertz, Blake; Martínez-Mayorga, Karina; Romo, Tod D.; Pitman, Michael C.; Feller, Scott E.; Grossfield, Alan; Brown, Michael F.

2014-01-01

Rhodopsin, the mammalian dim-light receptor, is one of the best-characterized G-protein-coupled receptors, a pharmaceutically important class of membrane proteins that has garnered a great deal of attention because of the recent availability of structural information. Yet the mechanism of rhodopsin activation is not fully understood. Here, we use microsecond-scale all-atom molecular dynamics simulations, validated by solid-state 2H nuclear magnetic resonance spectroscopy, to understand the transition between the dark and metarhodopsin I (Meta I) states. Our analysis of these simulations reveals striking differences in ligand flexibility between the two states. Retinal is much more dynamic in Meta I, adopting an elongated conformation similar to that seen in the recent activelike crystal structures. Surprisingly, this elongation corresponds to both a dramatic influx of bulk water into the hydrophobic core of the protein and a concerted transition in the highly conserved Trp2656.48 residue. In addition, enhanced ligand flexibility upon light activation provides an explanation for the different retinal orientations observed in X-ray crystal structures of active rhodopsin. PMID:24328554
Tartrazine modified activated carbon for the removal of Pb(II), Cd(II) and Cr(III).

PubMed

Monser, Lotfi; Adhoum, Nafaâ

2009-01-15

A two in one attempt for the removal of tartrazine and metal ions on activated carbon has been developed. The method was based on the modification of activated carbon with tartrazine then its application for the removal of Pb(II), Cd(II) and Cr(III) ions at different pH values. Tartrazine adsorption data were modelled using both Langmuir and Freundlich classical adsorption isotherms. The adsorption capacities qm were 121.3, 67 and 56.7mgg(-1) at initial pH values of 1.0, 6.0 and 10, respectively. The adsorption of tartrazine onto activated carbon followed second-order kinetic model. The equilibrium time was found to be 240min at pH 1.0 and 120min at pH 10 for 500mgL(-1) tartrazine concentration. A maximum removal of 85% was obtained after 1h of contact time. The presence of tartrazine as modifier enhances attractive electrostatic interactions between metal ions and carbon surface. The adsorption capacity for Pb(II), Cd(II) and Cr(III) ions has been improved with respect to non-modified carbon reaching a maximum of 140%. The adsorption capacity was found to be a pH dependent for both modified and non-modified carbon with a greater adsorption at higher pH values except for Cr(III). The enhancement percent of Pb(II), Cd(II) and Cr(III) at different pH values was varied from 28% to 140% with respect to non-modified carbon. The amount of metal ions adsorbed using static regime was 11-40% higher than that with dynamic mode. The difference between adsorption capacities could be attributed to the applied flow rate.
Structure of catabolite activator protein with cobalt(II) and sulfate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rao, Ramya R.; Lawson, Catherine L., E-mail: cathy.lawson@rutgers.edu

2014-04-15

The crystal structure of E. coli catabolite activator protein with bound cobalt(II) and sulfate ions at 1.97 Å resolution is reported. The crystal structure of cyclic AMP–catabolite activator protein (CAP) from Escherichia coli containing cobalt(II) chloride and ammonium sulfate is reported at 1.97 Å resolution. Each of the two CAP subunits in the asymmetric unit binds one cobalt(II) ion, in each case coordinated by N-terminal domain residues His19, His21 and Glu96 plus an additional acidic residue contributed via a crystal contact. The three identified N-terminal domain cobalt-binding residues are part of a region of CAP that is important for transcriptionmore » activation at class II CAP-dependent promoters. Sulfate anions mediate additional crystal lattice contacts and occupy sites corresponding to DNA backbone phosphate positions in CAP–DNA complex structures.« less
Adsorption of aqueous Cd(II) and Pb(II) on activated carbon nanopores prepared by chemical activation of doum palm shell.

PubMed

Gaya, Umar Ibrahim; Otene, Emmanuel; Abdullah, Abdul Halim

2015-01-01

Non-uniformly sized activated carbons were derived from doum palm shell, a new precursor, by carbonization in air and activation using KOH, NaOH and ZnCl2. The activated carbon fibres were characterised by X-ray diffraction, N2 adsorption-desorption, scanning electron microscopy, particle size analysis and evaluated for Cd(II) and Pb(II) removal. The 40-50 nm size, less graphitic, mesoporous NaOH activated carbon yielded high adsorption efficiency, pointing largely to the influence surface area. The performance of the KOH based activated carbon was arguably explained for the first time in terms of crystallinity. The efficiencies of the mesoporous ZnCl2-formulated activated carbon diminished due to the presence of larger particles. Batch adsorption of divalent metals revealed dependence on adsorbent dose, agitation time, pH and adsorbate concentrations with high adsorption efficiencies at optimum operating parameters. The equilibrium profiles fitted Langmuir and Freundlich isotherms, and kinetics favoured pseudo-second order model. The study demonstrated the practicability of the removal of alarming levels of cadmium and lead ions from industrial effluents.
Health Activities Project (HAP), Trial Edition II.

ERIC Educational Resources Information Center

Buller, Dave; And Others

Contained within this Health Activities Project (HAP) trial edition (set II) are a teacher information folio and numerous student activity folios which center around the idea that students in grades 5-8 can control their own health and safety. Each student folio is organized into a Synopsis, Health Background, Materials, Setting Up, and Activities…
Group II metabotropic glutamate receptor activation attenuates peripheral sensitization in inflammatory states

PubMed Central

Du, Junhui; Zhou, Shengtai; Carlton, Susan M.

2008-01-01

Several lines of evidence indicate that Group II metabotropic glutamate receptor (mGluR) activation can depress sensory transmission. We have reported the expression of Group II mGluRs on unmyelinated axons, many of which were presumed to be nociceptors, in the rat digital nerve (Carlton et al., 2001b). The goals of the present study are to further our understanding of Group II modulation of nociceptor processing in the periphery, documenting behavioral changes using inflammatory models and documenting, for the first time, cutaneous single fiber activity following exposure to a Group II agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) and antagonist LY341495 (LY). The data indicate that peripheral Group II mGluR activation does not depress nociceptive behaviors or nociceptor fiber responses in the non-sensitized state (i.e. following brief nociceptive mechanical or thermal stimulation) but can depress these responses when nociceptors are sensitized by exposure to formalin or inflammatory soup. Group II mGluR agonist-induced inhibition can be blocked by a selective Group II antagonist. Peripheral Group II mGluR-induced inhibition evoked in these studies occurs through activation of local receptors and not through spinal or supraspinal mechanisms. The data indicate that administration of selective Group II agonists may be potent therapeutic agents for prevention of peripheral sensitization and for treatment of inflammatory pain. PMID:18487022
Icariside II activates EGFR-Akt-Nrf2 signaling and protects osteoblasts from dexamethasone.

PubMed

Liu, Weidong; Mao, Li; Ji, Feng; Chen, Fengli; Wang, Shouguo; Xie, Yue

2017-01-10

The potential effect of icariside II on dexamethasone-induced osteoblast cell damages was evaluated here. In MC3T3-E1 osteoblastic cells and the primary murine osteoblasts, co-treatment with icariside II dramatically attenuated dexamethasone- induced cell death and apoptosis. Icariside II activated Akt signaling, which is required for its actions in osteoblasts. Akt inhibitors (LY294002, perifosine and MK-2206) almost abolished icariside II-induced osteoblast cytoprotection against dexamethasone. Further studies showed that icariside II activated Nrf2 signaling, downstream of Akt, to inhibit dexamethasone-induced reactive oxygen species (ROS) production in MC3T3-E1 cells and primary osteoblasts. On the other hand, Nrf2 shRNA knockdown inhibited icariside II-induced anti-dexamethasone cytoprotection in MC3T3-E1 cells. Finally, we showed that icariside II induced heparin-binding EGF (HB-EGF) production and EGFR trans-activation in MC3T3-E1 cells. EGFR inhibition, via anti-HB-EGF antibody, EGFR inhibitor AG1478 or EGFR shRNA knockdown, almost blocked icariside II-induced Akt-Nrf2 activation in MC3T3-E1 cells. Collectively, we conclude that icariside II activates EGFR-Akt-Nrf2 signaling and protects osteoblasts from dexamethasone. Icariside II might have translational value for the treatment of dexamethasone-associated osteoporosis/osteonecrosis.
Composition, Characterization and Antibacterial activity of Mn(II), Co(II),Ni(II), Cu(II) Zn(II) and Cd(II) mixed ligand complexes Schiff base derived from Trimethoprim with 8-Hydroxy quinoline

NASA Astrophysics Data System (ADS)

Numan, Ahmed T.; Atiyah, Eman M.; Al-Shemary, Rehab K.; Ulrazzaq, Sahira S. Abd

2018-05-01

New Schiff base ligand 2-((4-amino-5-(3, 4, 5-trimethoxybenzyl) pyrimidin-2-ylimino) (phenyl)methyl)benzoic acid] = [HL] was synthesized using microwave irradiation trimethoprim and 2-benzoyl benzoic acid. Mixed ligand complexes of Mn((II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) are reacted in ethanol with Schiff base ligand [HL] and 8-hydroxyquinoline [HQ] then reacted with metal salts in ethanol as a solvent in (1:1:1) ratio. The ligand [HL] is characterized by FTIR, UV-Vis, melting point, elemental microanalysis (C.H.N), 1H-NMR, 13C-NMR, and mass spectra. The mixed ligand complexes are characterized by infrared spectra, electronic spectra, (C.H.N), melting point, atomic absorption, molar conductance and magnetic moment measurements. These measurements indicate that the ligand [HL] coordinates with metal (II) ion in a tridentate manner through the oxygen and nitrogen atoms of the ligand, octahedral structures are suggested for these complexes. Antibacterial activity of the ligands [HL], [HQ] and their complexes are studied against (gram positive) and (gram negative) bacteria.
Chromospheric Activity in Population II Giants

NASA Technical Reports Server (NTRS)

Harper, Graham M.

2004-01-01

One of the mysteries of Population II giants is that they still show chromospheric emission despite their great age. The global dynamo which was active during their main-sequence lifetimes is expected to become extremely weak through magnetic rotational braking. The nature of the observed emission is not understood; although acoustic shock waves might provide the heating, acoustic waves are not predicted to drive the observed mass loss - which in turn requires the dissipation of magneto-hydrodynamic waves. This program was designed to search for the faint stellar H Ly beta emission wings and the fluorescent Fe II and H2 emission from one of the brightest, metal poor, Population II stars. These FUSE diagnostics, when combined with existing UV and optical spectra, help determine the major radiative cooling channels for the chromosphere. This observation was to complement that previously planned for the mildly metal deficient giant alpha Boo (K2 III). However, alpha Boo has yet to be observed with FUSE.
Synthesis, structural and biochemical activity studies of a new hexadentate Schiff base ligand and its Cu(II), Ni(II), and Co(II) complexes

NASA Astrophysics Data System (ADS)

Ekmekcioglu, Pinar; Karabocek, Nevin; Karabocek, Serdar; Emirik, Mustafa

2015-11-01

A new Schiff base ligand (H2L) and its metal complexes have been prepared and characterized by elemental analysis, magnetic moment and spectral studies. The comparative in-vitro antimicrobial activities against various pathogens with reference to known antibiotics activity under the standard control of different concentrations revealed that the metal complexes (6-8) showed enhanced antimicrobial activities in general as compared to free ligand. As an exception, the free ligand showed better activity against Trichoderma. The antifungal activity experiments were performed in triplicate. The order of biochemical activity for metal complexes were observed as in the following. CuL > CoL > NiL, which is exactly same as the order of stability constants of these complexes. Additionally, we performed DFT and TD-DFT calculation for free ligand and Cu(II) complex to support the experimental data. The geometries of the Cu(II) complex have been optimized using the B3LYP level of theory. The theoretical calculations confirm that the copper (II) center exhibits a distorted square pyramidal geometry which is favored by experimental results.
Arrestin-rhodopsin binding stoichiometry in isolated rod outer segment membranes depends on the percentage of activated receptors.

PubMed

Sommer, Martha E; Hofmann, Klaus Peter; Heck, Martin

2011-03-04

In the rod cell of the retina, arrestin is responsible for blocking signaling of the G-protein-coupled receptor rhodopsin. The general visual signal transduction model implies that arrestin must be able to interact with a single light-activated, phosphorylated rhodopsin molecule (Rho*P), as would be generated at physiologically relevant low light levels. However, the elongated bi-lobed structure of arrestin suggests that it might be able to accommodate two rhodopsin molecules. In this study, we directly addressed the question of binding stoichiometry by quantifying arrestin binding to Rho*P in isolated rod outer segment membranes. We manipulated the "photoactivation density," i.e. the percentage of active receptors in the membrane, with the use of a light flash or by partially regenerating membranes containing phosphorylated opsin with 11-cis-retinal. Curiously, we found that the apparent arrestin-Rho*P binding stoichiometry was linearly dependent on the photoactivation density, with one-to-one binding at low photoactivation density and one-to-two binding at high photoactivation density. We also observed that, irrespective of the photoactivation density, a single arrestin molecule was able to stabilize the active metarhodopsin II conformation of only a single Rho*P. We hypothesize that, although arrestin requires at least a single Rho*P to bind the membrane, a single arrestin can actually interact with a pair of receptors. The ability of arrestin to interact with heterogeneous receptor pairs composed of two different photo-intermediate states would be well suited to the rod cell, which functions at low light intensity but is routinely exposed to several orders of magnitude more light.

Formation and decay of the arrestin·rhodopsin complex in native disc membranes.

PubMed

Beyrière, Florent; Sommer, Martha E; Szczepek, Michal; Bartl, Franz J; Hofmann, Klaus Peter; Heck, Martin; Ritter, Eglof

2015-05-15

In the G protein-coupled receptor rhodopsin, light-induced cis/trans isomerization of the retinal ligand triggers a series of distinct receptor states culminating in the active Metarhodopsin II (Meta II) state, which binds and activates the G protein transducin (Gt). Long before Meta II decays into the aporeceptor opsin and free all-trans-retinal, its signaling is quenched by receptor phosphorylation and binding of the protein arrestin-1, which blocks further access of Gt to Meta II. Although recent crystal structures of arrestin indicate how it might look in a precomplex with the phosphorylated receptor, the transition into the high affinity complex is not understood. Here we applied Fourier transform infrared spectroscopy to monitor the interaction of arrestin-1 and phosphorylated rhodopsin in native disc membranes. By isolating the unique infrared signature of arrestin binding, we directly observed the structural alterations in both reaction partners. In the high affinity complex, rhodopsin adopts a structure similar to Gt-bound Meta II. In arrestin, a modest loss of β-sheet structure indicates an increase in flexibility but is inconsistent with a large scale structural change. During Meta II decay, the arrestin-rhodopsin stoichiometry shifts from 1:1 to 1:2. Arrestin stabilizes half of the receptor population in a specific Meta II protein conformation, whereas the other half decays to inactive opsin. Altogether these results illustrate the distinct binding modes used by arrestin to interact with different functional forms of the receptor. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
Program Activity/Training Plans. STIP II (Skill Training Improvement Programs Round II).

ERIC Educational Resources Information Center

Los Angeles Community Coll. District, CA.

Detailed operational guidelines, training objectives, and learning activities are provided for the Los Angeles Community College District's Skill Training Improvement Programs (STIP II), which are designed to train students for immediate employment. The first of four reports covers Los Angeles Southwest College's computer programming trainee…
Nitric oxide inhibits topoisomerase II activity and induces resistance to topoisomerase II-poisons in human tumor cells.

PubMed

Kumar, Ashutosh; Ehrenshaft, Marilyn; Tokar, Erik J; Mason, Ronald P; Sinha, Birandra K

2016-07-01

Etoposide and doxorubicin, topoisomerase II poisons, are important drugs for the treatment of tumors in the clinic. Topoisomerases contain several free sulfhydryl groups which are important for their activity and are also potential targets for nitric oxide (NO)-induced nitrosation. NO, a physiological signaling molecule nitrosates many cellular proteins, causing altered protein and cellular functions. Here, we have evaluated the roles of NO/NO-derived species in the activity/stability of topo II both in vitro and in human tumor cells, and in the cytotoxicity of topo II-poisons, etoposide and doxorubicin. Treatment of purified topo IIα with propylamine propylamine nonoate (PPNO), an NO donor, resulted in inhibition of both the catalytic and relaxation activity in vitro, and decreased etoposide-dependent cleavable complex formation in both human HT-29 colon and MCF-7 breast cancer cells. PPNO treatment also induced significant nitrosation of topo IIα protein in these human tumor cells. These events, taken together, caused a significant resistance to etoposide in both cell lines. However, PPNO had no effect on doxorubicin-induced cleavable complex formation, or doxorubicin cytotoxicity in these cell lines. Inhibition of topo II function by NO/NO-derived species induces significant resistance to etoposide, without affecting doxorubicin cytotoxicity in human tumor cells. As tumors express inducible nitric oxide synthase and generate significant amounts of NO, modulation of topo II functions by NO/NO-derived species could render tumors resistant to certain topo II-poisons in the clinic. Published by Elsevier B.V.
Mitotic Transcriptional Activation: Clearance of Actively Engaged Pol II via Transcriptional Elongation Control in Mitosis.

PubMed

Liang, Kaiwei; Woodfin, Ashley R; Slaughter, Brian D; Unruh, Jay R; Box, Andrew C; Rickels, Ryan A; Gao, Xin; Haug, Jeffrey S; Jaspersen, Sue L; Shilatifard, Ali

2015-11-05

Although it is established that some general transcription factors are inactivated at mitosis, many details of mitotic transcription inhibition (MTI) and its underlying mechanisms are largely unknown. We have identified mitotic transcriptional activation (MTA) as a key regulatory step to control transcription in mitosis for genes with transcriptionally engaged RNA polymerase II (Pol II) to activate and transcribe until the end of the gene to clear Pol II from mitotic chromatin, followed by global impairment of transcription reinitiation through MTI. Global nascent RNA sequencing and RNA fluorescence in situ hybridization demonstrate the existence of transcriptionally engaged Pol II in early mitosis. Both genetic and chemical inhibition of P-TEFb in mitosis lead to delays in the progression of cell division. Together, our study reveals a mechanism for MTA and MTI whereby transcriptionally engaged Pol II can progress into productive elongation and finish transcription to allow proper cellular division. Copyright © 2015 Elsevier Inc. All rights reserved.
The Ca II infrared triplet's performance as an activity indicator compared to Ca II H and K. Empirical relations to convert Ca II infrared triplet measurements to common activity indices

NASA Astrophysics Data System (ADS)

Martin, J.; Fuhrmeister, B.; Mittag, M.; Schmidt, T. O. B.; Hempelmann, A.; González-Pérez, J. N.; Schmitt, J. H. M. M.

2017-09-01

Aims: A large number of Calcium infrared triplet (IRT) spectra are expected from the Gaia and CARMENES missions. Conversion of these spectra into known activity indicators will allow analysis of their temporal evolution to a better degree. We set out to find such a conversion formula and to determine its robustness. Methods: We have compared 2274 Ca II IRT spectra of active main-sequence F to K stars taken by the TIGRE telescope with those of inactive stars of the same spectral type. After normalizing and applying rotational broadening, we subtracted the comparison spectra to find the chromospheric excess flux caused by activity. We obtained the total excess flux, and compared it to established activity indices derived from the Ca II H and K lines, the spectra of which were obtained simultaneously to the infrared spectra. Results: The excess flux in the Ca II IRT is found to correlate well with R'HK and R+HK, as well as SMWO, if the B - V-dependency is taken into account. We find an empirical conversion formula to calculate the corresponding value of one activity indicator from the measurement of another, by comparing groups of datapoints of stars with similar B - V.
Group II p21-activated kinases as therapeutic targets in gastrointestinal cancer.

PubMed

Shao, Yang-Guang; Ning, Ke; Li, Feng

2016-01-21

P21-activated kinases (PAKs) are central players in various oncogenic signaling pathways. The six PAK family members are classified into group I (PAK1-3) and group II (PAK4-6). Focus is currently shifting from group I PAKs to group II PAKs. Group II PAKs play important roles in many fundamental cellular processes, some of which have particular significance in the development and progression of cancer. Because of their important functions, group II PAKs have become popular potential drug target candidates. However, few group II PAKs inhibitors have been reported, and most do not exhibit satisfactory kinase selectivity and "drug-like" properties. Isoform- and kinase-selective PAK inhibitors remain to be developed. This review describes the biological activities of group II PAKs, the importance of group II PAKs in the development and progression of gastrointestinal cancer, and small-molecule inhibitors of group II PAKs for the treatment of cancer.
The effect of copper(II), iron(II) sulphate, and vitamin C combinations on the weak antimicrobial activity of (+)-catechin against Staphylococcus aureus and other microbes.

PubMed

Holloway, Andrew C; Mueller-Harvey, Irene; Gould, Simon W J; Fielder, Mark D; Naughton, Declan P; Kelly, Alison F

2012-12-01

Few attempts have been made to improve the activity of plant compounds with low antimicrobial efficacy. (+)-Catechin, a weak antimicrobial tea flavanol, was combined with putative adjuncts and tested against different species of bacteria. Copper(II) sulphate enhanced (+)-catechin activity against Pseudomonas aeruginosa but not Staphylococcus aureus, Proteus mirabilis or Escherichia coli. Attempts to raise the activity of (+)-catechin against two unresponsive species, S. aureus and E. coli, with iron(II) sulphate, iron(III) chloride, and vitamin C, showed that iron(II) enhanced (+)-catechin against S. aureus, but not E. coli; neither iron(III) nor combined iron(II) and copper(II), enhanced (+)-catechin activity against either species. Vitamin C enhanced copper(II) containing combinations against both species in the absence of iron(II). Catalase or EDTA added to active samples removed viability effects suggesting that active mixtures had produced H(2)O(2)via the action of added metal(II) ions. H(2)O(2) generation by (+)-catechin plus copper(II) mixtures and copper(II) alone could account for the principal effect of bacterial growth inhibition following 30 minute exposures as well as the antimicrobial effect of (+)-catechin-iron(II) against S. aureus. These novel findings about a weak antimicrobial flavanol contrast with previous knowledge of more active flavanols with transition metal combinations. Weak antimicrobial compounds like (+)-catechin within enhancement mixtures may therefore be used as efficacious agents. (+)-Catechin may provide a means of lowering copper(II) or iron(II) contents in certain crop protection and other products.
Elimination of Cu(II) toxicity by powdered waste sludge (PWS) addition to an activated sludge unit treating Cu(II) containing synthetic wastewater.

PubMed

Pamukoglu, M Yunus; Kargi, Fikret

2007-09-05

Copper(II) ion toxicity onto activated sludge organisms was eliminated by addition of powdered waste sludge (PWS) to the feed wastewater for removal of Cu(II) ions by biosorption before biological treatment. The synthetic feed wastewater containing 14 or 22 mgl(-1) Cu(II) was mixed with PWS in a mixing tank where Cu(II) ions were adsorbed onto PWS and the mixture was fed to a sedimentation tank to separate Cu(II) containing PWS from the feed wastewater. The activated sludge unit fed with the effluent of the sedimentation tank was operated at a hydraulic residence time (HRT) of 10h and sludge age (SRT) of 10 days. To investigate Cu(II), COD and toxicity removal performance of the activated sludge unit at different PWS loadings, the system was operated at different PWS loading rates (0.1-1 gPWSh(-1)) while the Cu(II) loading rate was constant throughout the operation. Percent copper, COD and toxicity removals increased with increasing PWS loading rate due to increased adsorption of Cu(II) onto PWS yielding low Cu(II) contents in the feed. Biomass concentration in the aeration tank increased and the sludge volume index (SVI) decreased with increasing PWS loading rate due to elimination of Cu(II) from the feed wastewater by PWS addition. PWS addition to the Cu(II) containing wastewater was proven to be effective for removal of Cu(II) by biosorption before biological treatment. Approximately, 1 gPWSh(-1) should be added for 28 mgCuh(-1) loading rate for complete removal of Cu(II) from the feed wastewater to obtain high COD removals in the activated sludge unit.
20 CFR 404.1311 - Ninety-day active service requirement for World War II veterans.

Code of Federal Regulations, 2011 CFR

2011-04-01

... World War II veterans. 404.1311 Section 404.1311 Employees' Benefits SOCIAL SECURITY ADMINISTRATION... Uniformed Services World War II Veterans § 404.1311 Ninety-day active service requirement for World War II veterans. (a) The 90 days of active service required for World War II veterans do not have to be...
Inhibitor-based validation of a homology model of the active-site of tripeptidyl peptidase II.

PubMed

De Winter, Hans; Breslin, Henry; Miskowski, Tamara; Kavash, Robert; Somers, Marijke

2005-04-01

A homology model of the active site region of tripeptidyl peptidase II (TPP II) was constructed based on the crystal structures of four subtilisin-like templates. The resulting model was subsequently validated by judging expectations of the model versus observed activities for a broad set of prepared TPP II inhibitors. The structure-activity relationships observed for the prepared TPP II inhibitors correlated nicely with the structural details of the TPP II active site model, supporting the validity of this model and its usefulness for structure-based drug design and pharmacophore searching experiments.
The Role of Angiotensin II/AT1 Receptor Signaling in Regulating Retinal Microglial Activation.

PubMed

Phipps, Joanna A; Vessey, Kirstan A; Brandli, Alice; Nag, Nupur; Tran, Mai X; Jobling, Andrew I; Fletcher, Erica L

2018-01-01

This study explored whether the proangiogenic factor Angiotensin II (AngII) had a direct effect on the activation state of microglia via the Angiotensin type 1 receptor (AT1-R). Microglial dynamic activity was investigated in live retinal flatmounts from adult Cx3Cr1+/GFP mice under control, AngII (5 μM) or AngII (5 μM) + candesartan (0.227 μM) conditions. The effects of intravitreal administration of AngII (10 mM) were also investigated at 24 hours, with retinae processed for immunocytochemistry, flow cytometry, or inflammatory quantitative PCR arrays. We found FACS isolated retinal microglia expressed AT1-R. In retinal flatmounts, microglia showed characteristic movement of processes under control conditions. Perfusion of AngII induced an immediate change in process length (-42%, P < 0.05) and activation state of microglia that was ameliorated by AT1-R blockade, suggesting a direct effect of AngII on microglia via the AT1-R. Intravitreal injection of AngII induced microglial activation after 24 hours, which was characterized by increased soma size (23%, P < 0.001) and decreased process length (20%, P < 0.05). Further analysis indicated a significant decrease in the number of microglial contacts with retinal neurons (saline 15.6 ± 2.31 versus AngII 7.8 ± 1.06, P < 0.05). Retinal cytokine and chemokine expression was modulated, indicative of an inflammatory retinal phenotype. We show that retinal microglia express AT1-R and their activation state is significantly altered by the angiogenic factor, AngII. Specifically, AngII may directly activate AT1-Rs on microglia and contribute to retinal inflammation. This may have implications for diseases like diabetic retinopathy where increases in AngII and inflammation have been shown to play an important role.
20 CFR 404.1311 - Ninety-day active service requirement for World War II veterans.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false Ninety-day active service requirement for... Uniformed Services World War II Veterans § 404.1311 Ninety-day active service requirement for World War II veterans. (a) The 90 days of active service required for World War II veterans do not have to be...
20 CFR 404.1311 - Ninety-day active service requirement for World War II veterans.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Ninety-day active service requirement for... Uniformed Services World War II Veterans § 404.1311 Ninety-day active service requirement for World War II veterans. (a) The 90 days of active service required for World War II veterans do not have to be...
20 CFR 404.1311 - Ninety-day active service requirement for World War II veterans.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Ninety-day active service requirement for... Uniformed Services World War II Veterans § 404.1311 Ninety-day active service requirement for World War II veterans. (a) The 90 days of active service required for World War II veterans do not have to be...
Synthesis, characterization, antibacterial activities and carbonic anhydrase enzyme inhibitor effects of new arylsulfonylhydrazone and their Ni(II), Co(II) complexes

NASA Astrophysics Data System (ADS)

Özdemir, Ümmühan Özmen; Arslan, Fatma; Hamurcu, Fatma

2010-01-01

Ethane sulfonic acide hydrazide ( esh: CH 3CH 2SO 2NHNH 2) derivatives as 5-methylsalicyl-aldehydeethanesulfonylhydrazone ( 5msalesh), 5-methyl-2-hydroxyacetophenoneethane sulfonylhydrazone ( 5mafesh) and their Ni(II), Co(II) complexes have been synthesized for the first time. The structure of these compounds has been investigated by elemental analysis, FT-IR, 1H NMR, 13C NMR, LC/MS, UV-vis spectrophotometric method, magnetic susceptibility, thermal studies and conductivity measurements. The antibacterial activities of synthesized compounds were studied against Gram positive bacteria; Staphylococcus aureus, Bacillus subtilis, Bacillus magaterium and Gram negative bacteria; Salmonella enteritidis, Escherichia coli by using the microdilution broth method. The biological activity screening showed that ligands have more activity than complexes against the tested bacteria. The inhibition activities of these compounds on carbonic anhydrase II (CA II) have been investigated by comparing IC 50 and Ki values and it has been found that 5msalesh and its complexes have more enzyme inhibition efficiency than other compounds.
Synthesis, characterization, computational studies, antimicrobial activities and carbonic anhydrase inhibitor effects of 2-hydroxy acetophenone-N-methyl p-toluenesulfonylhydrazone and its Co(II), Pd(II), Pt(II) complexes

NASA Astrophysics Data System (ADS)

Özbek, Neslihan; Alyar, Saliha; Memmi, Burcu Koçak; Gündüzalp, Ayla Balaban; Bahçeci, Zafer; Alyar, Hamit

2017-01-01

2-Hydroxyacetophenone-N-methyl p-toluenesulfonylhydrazone (afptsmh) derived from p-toluenesulfonicacid-1-methylhydrazide (ptsmh) and its Co(II), Pd(II), Pt(II) complexes were synthesized for the first time. Synthesized compounds were characterized by spectroscopic methods (FT-IR, 1Hsbnd 13C NMR, LC-MS, UV-vis), magnetic susceptibility and conductivity measurements. 1H and 13C shielding tensors for crystal structure of ligand were calculated with GIAO/DFT/B3LYP/6-311++G(d,p) methods in CDCl3. The vibrational band assignments were performed at B3LYP/6-311++G(d,p) theory level combined with scaled quantum mechanics force field (SQMFF) methodology. The antibacterial activities of synthesized compounds were studied against some Gram positive and Gram negative bacteria by using microdilution and disc diffusion methods. In vitro enzyme inhibitory effects of the compounds were measured by UV-vis spectrophotometer. The enzyme activities against human carbonic anhydrase II (hCA II) were evaluated as IC50 (the half maximal inhibitory concentration) values. It was found that afptsmh and its metal complexes have inhibitory effects on hCA II isoenzyme. General esterase activities were determined using alpha and beta naphtyl acetate substrates (α- and β-NAs) of Drosophila melanogaster (D. melanogaster). Activity results show that afptsmh does not strongly affect the bacteria strains and also shows poor inhibitory activity against hCAII isoenzyme whereas all complexes posses higher biological activities.
Chronic inhibition of Ca(2+)/calmodulin kinase II activity in the pilocarpine model of epilepsy.

PubMed

Churn, S B; Kochan, L D; DeLorenzo, R J

2000-09-01

The development of symptomatic epilepsy is a model of long-term plasticity changes in the central nervous system. The rat pilocarpine model of epilepsy was utilized to study persistent alterations in calcium/calmodulin-dependent kinase II (CaM kinase II) activity associated with epileptogenesis. CaM kinase II-dependent substrate phosphorylation and autophosphorylation were significantly inhibited for up to 6 weeks following epileptogenesis in both the cortex and hippocampus, but not in the cerebellum. The net decrease in CaM kinase II autophosphorylation and substrate phosphorylation was shown to be due to decreased kinase activity and not due to increased phosphatase activity. The inhibition in CaM kinase II activity and the development of epilepsy were blocked by pretreating seizure rats with MK-801 indicating that the long-lasting decrease in CaM kinase II activity was dependent on N-methyl-D-aspartate receptor activation. In addition, the inhibition of CaM kinase II activity was associated in time and regional localization with the development of spontaneous recurrent seizure activity. The decrease in enzyme activity was not attributed to a decrease in the alpha or beta kinase subunit protein expression level. Thus, the significant inhibition of the enzyme occurred without changes in kinase protein expression, suggesting a long-lasting, post-translational modification of the enzyme. This is the first published report of a persistent, post-translational alteration of CaM kinase II activity in a model of epilepsy characterized by spontaneous recurrent seizure activity.
The B2 Alternatively Spliced Isoform of Nonmuscle Myosin II-B Lacks Actin-activated MgATPase Activity and In Vitro Motility

PubMed Central

Kim, Kye-Young; Kawamoto, Sachiyo; Bao, Jianjun; Sellers, James R.; Adelstein, Robert S.

2008-01-01

We report the initial biochemical characterization of an alternatively spliced isoform of nonmuscle heavy meromyosin (HMM) II-B2 and compare it with HMM II-B0, the non-spliced isoform. HMM II-B2 is the HMM derivative of an alternatively spliced isoform of endogenous nonmuscle myosin (NM) II-B, which has 21-amino acids inserted into loop 2, near the actin-binding region. NM II-B2 is expressed in the Purkinje cells of the cerebellum as well as in other neuronal cells (Ma et al., Mol. Biol. Cell 15 (2006) 2138-2149). In contrast to any of the previously described isoforms of NM II (II-A, II-B0, II-B1, II-C0 and II-C1) or to smooth muscle myosin, the actin-activated MgATPase activity of HMM II-B2 is not significantly increased from a low, basal level by phosphorylation of the 20 kDa myosin light chain (MLC-20). Moreover, although HMM II-B2 can bind to actin in the absence of ATP and is released in its presence, it cannot propel actin in the sliding actin filament assay following MLC-20 phosphorylation. Unlike HMM II-B2, the actin-activated MgATPase activity of a chimeric HMM with the 21-amino acids II-B2 sequence inserted into the homologous location in the heavy chain of HMM II-C is increased following MLC-20 phosphorylation. This indicates that the effect of the II-B2 insert is myosin heavy chain specific. PMID:18060863
Antimicrobial and mutagenic activity of some carbono- and thiocarbonohydrazone ligands and their copper(II), iron(II) and zinc(II) complexes.

PubMed

Bacchi, A; Carcelli, M; Pelagatti, P; Pelizzi, C; Pelizzi, G; Zani, F

1999-06-15

Several mono- and bis- carbono- and thiocarbonohydrazone ligands have been synthesised and characterised; the X-ray diffraction analysis of bis(phenyl 2-pyridyl ketone) thiocarbonohydrazone is reported. The coordinating properties of the ligands have been studied towards Cu(II), Fe(II), and Zn(II) salts. The ligands and the metal complexes were tested in vitro against Gram positive and Gram negative bacteria, yeasts and moulds. In general, the bisthiocarbonohydrazones possess the best antimicrobial properties and Gram positive bacteria are the most sensitive microorganisms. Bis(ethyl 2-pyridyl ketone) thiocarbonohydrazone, bis(butyl 2-pyridyl ketone)thiocarbonohydrazone and Cu(H2nft)Cl2 (H2nft, bis(5-nitrofuraldehyde)thiocarbonohydrazone) reveal a strong activity with minimum inhibitory concentrations of 0.7 microgram ml-1 against Bacillus subtilis and of 3 micrograms ml-1 against Staphylococcus aureus. Cu(II) complexes are more effective than Fe(II) and Zn(II) ones. All bisthiocarbono- and carbonohydrazones are devoid of mutagenic properties, with the exception of the compounds derived from 5-nitrofuraldehyde. On the contrary a weak mutagenicity, that disappears in the copper complexes, is exhibited by monosubstituted thiocarbonohydrazones.
Sulforaphane Prevents Angiotensin II-Induced Testicular Cell Death via Activation of NRF2.

PubMed

Wang, Yonggang; Wu, Hao; Xin, Ying; Bai, Yang; Kong, Lili; Tan, Yi; Liu, Feng; Cai, Lu

2017-01-01

Although angiotensin II (Ang II) was reported to facilitate sperm motility and intratesticular sperm transport, recent findings shed light on the efficacy of Ang II in stimulating inflammatory events in testicular peritubular cells, effect of which may play a role in male infertility. It is still unknown whether Ang II can induce testicular apoptotic cell death, which may be a more direct action of Ang II in male infertility. Therefore, the present study aims to determine whether Ang II can induce testicular apoptotic cell death and whether this action can be prevented by sulforaphane (SFN) via activating nuclear factor (erythroid-derived 2)-like 2 (NRF2), the governor of antioxidant-redox signalling. Eight-week-old male C57BL/6J wild type (WT) and Nrf2 gene knockout mice were treated with Ang II, in the presence or absence of SFN. In WT mice, SFN activated testicular NRF2 expression and function, along with a marked attenuation in Ang II-induced testicular oxidative stress, inflammation, endoplasmic reticulum stress, and apoptotic cell death. Deletion of the Nrf2 gene led to a complete abolishment of these efficacies of SFN. The present study indicated that Ang II may result in testicular apoptotic cell death, which can be prevented by SFN via the activation of NRF2.

Mn(II) Oxidation by the Multicopper Oxidase Complex Mnx: A Binuclear Activation Mechanism.

PubMed

Soldatova, Alexandra V; Tao, Lizhi; Romano, Christine A; Stich, Troy A; Casey, William H; Britt, R David; Tebo, Bradley M; Spiro, Thomas G

2017-08-23

The bacterial protein complex Mnx contains a multicopper oxidase (MCO) MnxG that, unusually, catalyzes the two-electron oxidation of Mn(II) to MnO 2 biomineral, via a Mn(III) intermediate. Although Mn(III)/Mn(II) and Mn(IV)/Mn(III) reduction potentials are expected to be high, we find a low reduction potential, 0.38 V (vs Normal Hydrogen Electrode, pH 7.8), for the MnxG type 1 Cu 2+ , the electron acceptor. Indeed the type 1 Cu 2+ is not reduced by Mn(II) in the absence of molecular oxygen, indicating that substrate oxidation requires an activation step. We have investigated the enzyme mechanism via electronic absorption spectroscopy, using chemometric analysis to separate enzyme-catalyzed MnO 2 formation from MnO 2 nanoparticle aging. The nanoparticle aging time course is characteristic of nucleation and particle growth; rates for these processes followed expected dependencies on Mn(II) concentration and temperature, but exhibited different pH optima. The enzymatic time course is sigmoidal, signaling an activation step, prior to turnover. The Mn(II) concentration and pH dependence of a preceding lag phase indicates weak Mn(II) binding. The activation step is enabled by a pK a > 8.6 deprotonation, which is assigned to Mn(II)-bound H 2 O; it induces a conformation change (consistent with a high activation energy, 106 kJ/mol) that increases Mn(II) affinity. Mnx activation is proposed to decrease the Mn(III/II) reduction potential below that of type 1 Cu(II/I) by formation of a hydroxide-bridged binuclear complex, Mn(II)(μ-OH)Mn(II), at the substrate site. Turnover is found to depend cooperatively on two Mn(II) and is enabled by a pK a 7.6 double deprotonation. It is proposed that turnover produces a Mn(III)(μ-OH) 2 Mn(III) intermediate that proceeds to the enzyme product, likely Mn(IV)(μ-O) 2 Mn(IV) or an oligomer, which subsequently nucleates MnO 2 nanoparticles. We conclude that Mnx exploits manganese polynuclear chemistry in order to facilitate an otherwise
Myosin II Activity Softens Cells in Suspension.

PubMed

Chan, Chii J; Ekpenyong, Andrew E; Golfier, Stefan; Li, Wenhong; Chalut, Kevin J; Otto, Oliver; Elgeti, Jens; Guck, Jochen; Lautenschläger, Franziska

2015-04-21

The cellular cytoskeleton is crucial for many cellular functions such as cell motility and wound healing, as well as other processes that require shape change or force generation. Actin is one cytoskeleton component that regulates cell mechanics. Important properties driving this regulation include the amount of actin, its level of cross-linking, and its coordination with the activity of specific molecular motors like myosin. While studies investigating the contribution of myosin activity to cell mechanics have been performed on cells attached to a substrate, we investigated mechanical properties of cells in suspension. To do this, we used multiple probes for cell mechanics including a microfluidic optical stretcher, a microfluidic microcirculation mimetic, and real-time deformability cytometry. We found that nonadherent blood cells, cells arrested in mitosis, and naturally adherent cells brought into suspension, stiffen and become more solidlike upon myosin inhibition across multiple timescales (milliseconds to minutes). Our results hold across several pharmacological and genetic perturbations targeting myosin. Our findings suggest that myosin II activity contributes to increased whole-cell compliance and fluidity. This finding is contrary to what has been reported for cells attached to a substrate, which stiffen via active myosin driven prestress. Our results establish the importance of myosin II as an active component in modulating suspended cell mechanics, with a functional role distinctly different from that for substrate-adhered cells. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Effect of calcium on the hemolytic activity of Stichodactyla helianthus toxin sticholysin II on human erythrocytes.

PubMed

Celedón, Gloria; González, Gustavo; Lissi, Eduardo; Cerda, Tania; Martinez, Diana; Soto, Carmen; Pupo, Mario; Pazos, Fabiola; Lanio, Maria E; Alvarez, Carlos

2009-11-01

Sticholysin II (St II) is a toxin from the sea anemona Stichodactyla helianthus that produces erythrocytes lysis at low concentration and its activity depends on the presence of calcium. Calcium may act modifying toxin interaction with erythrocyte membranes or activating cellular processes which may result in a modified St II lytic action. In this study we are reporting that, in the presence of external K(+), extracellular calcium decreased St II activity on erythrocytes. On the other hand an increase of intracellular calcium promotes Sty II lytic activity. The effect of intracellular calcium was specifically studied in relation to membrane lipid translocation elicited by scramblases and how this action influence St II lytic activity on erythrocytes. We used 0.5 mmol/L calcium and 10 mmol/L A23187, as calcium ionophore, for scramblases activation and found increased St II activity associated to increase of intracellular calcium. N-ethyl maleimide (activator) and 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (inhibitor) were used as scramblases modulators in the assays which produced an increase and a decrease of the calcium effect, respectively. Results reported suggest an improved St II membrane pore-forming capacity promoted by intracellular calcium associated to membrane phospholipids translocation.
20 CFR 404.1321 - Ninety-day active service requirement for post-World War II veterans.

Code of Federal Regulations, 2012 CFR

2012-04-01

... post-World War II veterans. 404.1321 Section 404.1321 Employees' Benefits SOCIAL SECURITY... of the Uniformed Services Post-World War II Veterans § 404.1321 Ninety-day active service requirement for post-World War II veterans. (a) The 90 days of active service required for post-World War II...
20 CFR 404.1321 - Ninety-day active service requirement for post-World War II veterans.

Code of Federal Regulations, 2013 CFR

2013-04-01

... post-World War II veterans. 404.1321 Section 404.1321 Employees' Benefits SOCIAL SECURITY... of the Uniformed Services Post-World War II Veterans § 404.1321 Ninety-day active service requirement for post-World War II veterans. (a) The 90 days of active service required for post-World War II...
20 CFR 404.1321 - Ninety-day active service requirement for post-World War II veterans.

Code of Federal Regulations, 2014 CFR

2014-04-01

... post-World War II veterans. 404.1321 Section 404.1321 Employees' Benefits SOCIAL SECURITY... of the Uniformed Services Post-World War II Veterans § 404.1321 Ninety-day active service requirement for post-World War II veterans. (a) The 90 days of active service required for post-World War II...
20 CFR 404.1321 - Ninety-day active service requirement for post-World War II veterans.

Code of Federal Regulations, 2011 CFR

2011-04-01

... post-World War II veterans. 404.1321 Section 404.1321 Employees' Benefits SOCIAL SECURITY... of the Uniformed Services Post-World War II Veterans § 404.1321 Ninety-day active service requirement for post-World War II veterans. (a) The 90 days of active service required for post-World War II...
Oligomeric state regulated trafficking of human platelet-activating factor acetylhydrolase type-II.

PubMed

Monillas, Elizabeth S; Caplan, Jeffrey L; Thévenin, Anastasia F; Bahnson, Brian J

2015-05-01

The intracellular enzyme platelet-activating factor acetylhydrolase type-II (PAFAH-II) hydrolyzes platelet-activating factor and oxidatively fragmented phospholipids. PAFAH-II in its resting state is mainly cytoplasmic, and it responds to oxidative stress by becoming increasingly bound to endoplasmic reticulum and Golgi membranes. Numerous studies have indicated that this enzyme is essential for protecting cells from oxidative stress induced apoptosis. However, the regulatory mechanism of the oxidative stress response by PAFAH-II has not been fully resolved. Here, changes to the oligomeric state of human PAFAH-II were investigated as a potential regulatory mechanism toward enzyme trafficking. Native PAGE analysis in vitro and photon counting histogram within live cells showed that PAFAH-II is both monomeric and dimeric. A Gly-2-Ala site-directed mutation of PAFAH-II demonstrated that the N-terminal myristoyl group is required for homodimerization. Additionally, the distribution of oligomeric PAFAH-II is distinct within the cell; homodimers of PAFAH-II were localized to the cytoplasm while monomers were associated to the membranes of the endoplasmic reticulum and Golgi. We propose that the oligomeric state of PAFAH-II drives functional protein trafficking. PAFAH-II localization to the membrane is critical for substrate acquisition and effective oxidative stress protection. It is hypothesized that the balance between monomer and dimer serves as a regulatory mechanism of a PAFAH-II oxidative stress response. Copyright © 2015 Elsevier B.V. All rights reserved.
Pharmacophore Hybridization To Discover Novel Topoisomerase II Poisons with Promising Antiproliferative Activity.

PubMed

Ortega, Jose Antonio; Riccardi, Laura; Minniti, Elirosa; Borgogno, Marco; Arencibia, Jose M; Greco, Maria L; Minarini, Anna; Sissi, Claudia; De Vivo, Marco

2018-02-08

We used a pharmacophore hybridization strategy to combine key structural elements of merbarone and etoposide and generated new type II topoisomerase (topoII) poisons. This first set of hybrid topoII poisons shows promising antiproliferative activity on human cancer cells, endorsing their further exploration for anticancer drug discovery.
DNA Binding, Cleavage and Antibacterial Activity of Mononuclear Cu(II), Ni(II) and Co(II) Complexes Derived from Novel Benzothiazole Schiff Bases.

PubMed

Vamsikrishna, Narendrula; Kumar, Marri Pradeep; Tejaswi, Somapangu; Rambabu, Aveli; Shivaraj

2016-07-01

A series of novel bivalent metal complexes M(L1)2 and M(L2)2 where M = Cu(II), Ni(II), Co(II) and L1 = 2-((benzo [d] thiazol-6-ylimino)methyl)-4-bromophenol [BTEMBP], L2 = 1-((benzo [d] thiazol-6-ylimino)methyl) naphthalen-2-ol [BTEMNAPP] were synthesized. All the compounds have been characterized by elemental analysis, SEM, Mass, (1)H NMR, (13)C NMR, UV-Vis, IR, ESR, spectral data and magnetic susceptibility measurements. Based on the analytical and spectral data four-coordinated square planar geometry is assigned to all the complexes. DNA binding properties of these complexes have been investigated by electronic absorption spectroscopy, fluorescence and viscosity measurements. It is observed that these binary complexes strongly bind to calf thymus DNA by an intercalation mode. DNA cleavage efficacy of these complexes was tested in presence of H2O2 and UV light by gel electrophoresis and found that all the complexes showed better nuclease activity. Finally the compounds were screened for antibacterial activity against few pathogens and found that the complexes have potent biocidal activity than their free ligands.
Removal of mercury (II) from aqueous solution by activated carbon obtained from furfural.

PubMed

Yardim, M F; Budinova, T; Ekinci, E; Petrov, N; Razvigorova, M; Minkova, V

2003-08-01

The adsorption of Hg(II) from aqueous solution at 293 K by activated carbon obtained from furfural is studied. The carbon is prepared by polymerization of furfural following carbonization and activation of the obtained polymer material with water vapor at 800 degrees C. Adsorption studies of Hg(II) are carried out varying some conditions: treatment time, metal ion concentration, adsorbent amount and pH. It is determined that Hg(II) adsorption follows both Langmuir and Freundlich isotherms. The adsorption capacity of the carbon is 174 mg/g. It is determined that Hg(II) uptake increases with increasing pH. Desorption studies are performed with hot water. The percent recovery of Hg(II) is 6%.
Performance of Spent Mushroom Farming Waste (SMFW) Activated Carbon for Ni (II) Removal

NASA Astrophysics Data System (ADS)

Desa, N. S. Md; Ghani, Z. Ab; Talib, S. Abdul; Tay, C. C.

2016-07-01

The feasibility of a low cost agricultural waste of spent mushroom farming waste (SMFW) activated carbon for Ni(II) removal was investigated. The batch adsorption experiments of adsorbent dosage, pH, contact time, metal concentration, and temperature were determined. The samples were shaken at 125 rpm, filtered and analyzed using ICP-OES. The fifty percent of Ni(II) removal was obtained at 0.63 g of adsorbent dosage, pH 5-6 (unadjusted), 60 min contact time, 50 mg/L Ni(II) concentration and 25 °C temperature. The evaluated SMFW activated carbon showed the highest performance on Ni(II) removal compared to commercial Amberlite IRC86 resin and zeolite NK3. The result indicated that SMFW activated carbon is a high potential cation exchange adsorbent and suitable for adsorption process for metal removal. The obtained results contribute toward application of developed SMFW activated carbon in industrial pilot study.
Ligational behaviour of lomefloxacin drug towards Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Th(IV) and UO(2)(VI) ions: synthesis, structural characterization and biological activity studies.

PubMed

Abd el-Halim, Hanan F; Mohamed, Gehad G; el-Dessouky, Maher M I; Mahmoud, Walaa H

2011-11-01

Nine new mononuclear Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Th(IV) and UO(2)(VI) complexes of lomefloxacin drug were synthesized. The structures of these complexes were elucidated by elemental analyses, IR, XRD, UV-vis, (1)H NMR as well as conductivity and magnetic susceptibility measurements and thermal analyses. The dissociation constants of lomefloxacin and stability constants of its binary complexes have been determined spectrophotometrically in aqueous solution at 25±1°C and at 0.1 M KNO(3) ionic strength. The discussion of the outcome data of the prepared complexes indicate that the lomefloxacin ligand behaves as a neutral bidentate ligand through OO coordination sites and coordinated to the metal ions via the carbonyl oxygen and protonated carboxylic oxygen with 1:1 (metal:ligand) stoichiometry for all complexes. The molar conductance measurements proved that the complexes are electrolytes. The powder XRD study reflects the crystalline nature for the investigated ligand and its complexes except Mn(II), Zn(II) and UO(2)(II). The geometrical structures of these complexes are found to be octahedral. The thermal behaviour of these chelates is studied where the hydrated complexes lose water molecules of hydration in the first steps followed by decomposition of the anions, coordinated water and ligand molecules in the subsequent steps. The activation thermodynamic parameters are calculated using Coats-Redfern and Horowitz-Metzger methods. A comparative study of the inhibition zones of the ligand and its metal complexes indicates that metal complexes exhibit higher antibacterial effect against one or more bacterial species than the free LFX ligand. The antifungal and anticancer activities were also tested. The antifungal effect of almost metal complexes is higher than the free ligand. LFX, [Co(LFX)(H(2)O)(4)]·Cl(2) and [Zn(LFX)(H(2)O)(4)]·Cl(2) were found to be very active with IC50 values 14, 11.2 and 43.1, respectively. While, other
Synthesis and characterization of new complexes of nickel (II), palladium (II) and platinum(II) with derived sulfonamide ligand: Structure, DFT study, antibacterial and cytotoxicity activities

NASA Astrophysics Data System (ADS)

Bouchoucha, Afaf; Zaater, Sihem; Bouacida, Sofiane; Merazig, Hocine; Djabbar, Safia

2018-06-01

The synthesis, characterization and biological study of new nickel (II), palladium (II), and platinum (II) complexes with sulfamethoxazole ligand used in pharmaceutical field, were reported. [MLCl2].nH2O is the general formula obtained for Pd(II) and Pt(II) complexes. These complexes have been prepared and characterized by elemental analysis, FTIR, 1HNMR spectral, magnetic measurements, UV-Visible spectra, and conductivity. The DFT calculation was applied to optimize the geometric structure of the Pd(II) and Pt(II) complexes. A new single-crystal X-ray structure of the Ni(II) complex has been determined. It crystallized in monoclinic system with P 21/c space group and Z = 8. The invitro antibacterial activity of ligand and complexes against Escherichia coli, P. aeruginosa, Klebsiella pneumoniae, S. aureus, Bacillus subtilis species has been carried out and compared using agar-diffusion method. The Pd(II) and Pt(II) complexes showed a remarkable inhibition against bacteria tested. The invitro cytotoxicity assay of the complexes against three cell lines chronic myelogenous leukaemia (K562), human colon adenocarcinoma (HT-29) and breast cancer (MCF-7) was also reported.
Subneurotoxic copper(II)-induced NF-κB-dependent microglial activation is associated with mitochondrial ROS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Zhuqin; Yu, Fengxiang; Gong, Ping

2014-04-15

Microglia-mediated neuroinflammation and the associated neuronal damage play critical roles in the pathogenesis of neurodegenerative disorders. Evidence shows an elevated concentration of extracellular copper(II) in the brains of these disorders, which may contribute to neuronal death through direct neurotoxicity. Here we explored whether extracellular copper(II) triggers microglial activation. Primary rat microglia and murine microglial cell line BV-2 cells were cultured and treated with copper(II). The content of tumor necrosis factor-α (TNF-α) and nitric oxide in the medium was determined. Extracellular hydrogen peroxide was quantified by a fluorometric assay with Amplex Red. Mitochondrial superoxide was measured by MitoSOX oxidation. At subneurotoxicmore » concentrations, copper(II) treatment induced a dose- and time-dependent release of TNF-α and nitric oxide from microglial cells, and caused an indirect, microglia-mediated neurotoxicity that was blocked by inhibition of TNF-α and nitric oxide production. Copper(II)-initiated microglial activation was accompanied with reduced IkB-α expression as well as phosphorylation and translocation of nuclear factor-κB (NF-κB) p65 and was blocked by NF-κB inhibitors (BAY11-7082 and SC-514). Moreover, copper(II) treatment evoked a rapid release of hydrogen peroxide from microglial cells, an effect that was not affected by NADPH oxidase inhibitors. N-acetyl-cysteine, a scavenger of reactive oxygen species (ROS), abrogated copper(II)-elicited microglial release of TNF-α and nitric oxide and subsequent neurotoxicity. Importantly, mitochondrial production of superoxide, paralleled to extracellular release of hydrogen peroxide, was induced after copper(II) stimulation. Our findings suggest that extracellular copper(II) at subneurotoxic concentrations could trigger NF-κB-dependent microglial activation and subsequent neurotoxicity. NADPH oxidase-independent, mitochondria-derived ROS may be involved in this activation
Synthesis, structural characterization, and pro-apoptotic activity of 1-indanone thiosemicarbazone platinum(II) and palladium(II) complexes: potential as antileukemic agents.

PubMed

Gómez, Natalia; Santos, Diego; Vázquez, Ramiro; Suescun, Leopoldo; Mombrú, Alvaro; Vermeulen, Monica; Finkielsztein, Liliana; Shayo, Carina; Moglioni, Albertina; Gambino, Dinorah; Davio, Carlos

2011-08-01

In the search for alternative chemotherapeutic strategies against leukemia, various 1-indanone thiosemicarbazones, as well as eight novel platinum(II) and palladium(II) complexes, with the formula [MCl₂(HL)] and [M(HL)(L)]Cl, derived from two 1-indanone thiosemicarbazones were synthesized and tested for antiproliferative activity against the human leukemia U937 cell line. The crystal structure of [Pt(HL1)(L1)]Cl·2MeOH, where L1=1-indanone thiosemicarbazone, was solved by X-ray diffraction. Free thiosemicarbazone ligands showed no antiproliferative effect, but the corresponding platinum(II) and palladium(II) complexes inhibited cell proliferation and induced apoptosis. Platinum(II) complexes also displayed selective apoptotic activity in U937 cells but not in peripheral blood monocytes or the human hepatocellular carcinoma HepG2 cell line used to screen for potential hepatotoxicity. Present findings show that, in U937 cells, 1-indanone thiosemicarbazones coordinated to palladium(II) were more cytotoxic than those complexed with platinum(II), although the latter were found to be more selective for leukemic cells suggesting that they are promising compounds with potential therapeutic application against hematological malignancies. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Synthesis and topoisomerase II inhibitory and cytotoxic activity of oxiranylmethoxy- and thiiranylmethoxy-chalcone derivatives.

PubMed

Na, Younghwa; Nam, Jung-Min

2011-01-01

In order to find potential anticancer drug candidate targeting topoisomerases enzyme, we have designed and synthesized oxiranylmethoxy- and thiiranylmethoxy-retrochalcone derivatives and evaluated their pharmacological activity including topoisomerases inhibitory and cytotoxic activity. Of the compounds prepared compound 25 showed comparable or better cytotoxic activity against cancer cell lines tested. Compound 25 inhibited MCF7 (IC(50): 0.49 ± 0.21 μM) and HCT15 (IC(50): 0.23 ± 0.02 μM) carcinoma cell growth more efficiently than references. In the topoisomerases inhibition test, all the compounds were inactive to topoisomerase I but moderate inhibitors to topoisomerase II enzyme. Especially, compound 25 inhibited topoisomerase II activity with comparable extent to etoposide at 100 μM concentrations. Correlation between cytotoxicity and topoisomerase II inhibitory activity implies that compound 25 can be a possible lead compound for anticancer drug impeding the topoisomerase II function. Copyright © 2010 Elsevier Ltd. All rights reserved.
Synthesis, characterization, and anti-cancer activity of emodin-Mn(II) metal complex.

PubMed

Yang, Li; Tan, Jun; Wang, Bo-Chu; Zhu, Lian-Cai

2014-12-01

To synthesize and characterize a novel metal complex of Mn (II) with emodin, and evaluate its anti-cancer activity. The elemental analyses, IR, UV-vis, atomic absorption spectroscopy, TG-DSC, (1)H NMR, and (13)C NMR data were used to characterize the structure of the complex. The cytotoxicity of the complex against the human cancer cell lines HepG2, HeLa, MCF-7, B16, and MDA-MB-231 was tested by the MTT assay and flow cytometry. Emodin was coordinated with Mn(II) through the 9-C=O and 1-OH, and the general formula of the complex was Mn(II) (emodin)2·2H2O. In studies of the cytotoxicity, the complex exhibited significant activity, and the IC50 values of the complex against five cancer cell lines improved approximately three-fold compared with those of emodin. The complex could induce cell morphological changes, decrease the percentage of viability, and induce G0/G1 phase arrest and apoptosis in cancer cells. The coordination of emodin with Mn(II) can improve its anticancer activity, and the complex Mn(II) (emodin)2·2H2O could be studied further as a promising anticancer drug. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
Alkyl sulfonic acide hydrazides: Synthesis, characterization, computational studies and anticancer, antibacterial, anticarbonic anhydrase II (hCA II) activities

NASA Astrophysics Data System (ADS)

O. Ozdemir, Ummuhan; İlbiz, Firdevs; Balaban Gunduzalp, Ayla; Ozbek, Neslihan; Karagoz Genç, Zuhal; Hamurcu, Fatma; Tekin, Suat

2015-11-01

Methane sulfonic acide hydrazide, CH3SO2NHNH2 (1), ethane sulfonic acide hydrazide, CH3CH2SO2NHNH2 (2), propane sulfonic acide hydrazide, CH3CH2CH2SO2NHNH2 (3) and butane sulfonic acide hydrazide, CH3CH2CH2CH2SO2NHNH2 (4) have been synthesized as homologous series and characterized by using elemental analysis, spectrophotometric methods (1H-13C NMR, FT-IR, LC-MS). In order to gain insight into the structure of the compounds, we have performed computational studies by using 6-311G(d, p) functional in which B3LYP functional were implemented. The geometry of the sulfonic acide hydrazides were optimized at the DFT method with Gaussian 09 program package. A conformational analysis of compounds were performed by using NMR theoretical calculations with DFT/B3LYP/6-311++G(2d, 2p) level of theory by applying the (GIAO) approach. The anticancer activities of these compounds on MCF-7 human breast cancer cell line investigated by comparing IC50 values. The antibacterial activities of synthesized compounds were studied against Gram positive bacteria; Staphylococcus aureus ATCC 6538, Bacillus subtilis ATCC 6633, Bacillus cereus NRRL-B-3711, Enterococcus faecalis ATCC 29212 and Gram negative bacteria; Escherichia coli ATCC 11230, Pseudomonas aeruginosa ATCC 15442, Klebsiella pneumonia ATCC 70063 by using the disc diffusion method. The inhibition activities of these compounds on carbonic anhydrase II enzyme (hCA II) have been investigated by comparing IC50 and Ki values. The biological activity screening shows that butane sulfonic acide hydrazide (4) has more activity than the others against tested breast cancer cell lines MCF-7, Gram negative/Gram positive bacteria and carbonic anhydrase II (hCA II) isoenzyme.
Calcium/calmodulin-dependent protein kinase II activity regulates the proliferative potential of growth plate chondrocytes.

PubMed

Li, Yuwei; Ahrens, Molly J; Wu, Amy; Liu, Jennifer; Dudley, Andrew T

2011-01-01

For tissues that develop throughout embryogenesis and into postnatal life, the generation of differentiated cells to promote tissue growth is at odds with the requirement to maintain the stem cell/progenitor cell population to preserve future growth potential. In the growth plate cartilage, this balance is achieved in part by establishing a proliferative phase that amplifies the number of progenitor cells prior to terminal differentiation into hypertrophic chondrocytes. Here, we show that endogenous calcium/calmodulin-dependent protein kinase II (CamkII, also known as Camk2) activity is upregulated prior to hypertrophy and that loss of CamkII function substantially blocks the transition from proliferation to hypertrophy. Wnt signaling and Pthrp-induced phosphatase activity negatively regulate CamkII activity. Release of this repression results in activation of multiple effector pathways, including Runx2- and β-catenin-dependent pathways. We present an integrated model for the regulation of proliferation potential by CamkII activity that has important implications for studies of growth control and adult progenitor/stem cell populations.

Chemically modified activated carbon with 1-acylthiosemicarbazide for selective solid-phase extraction and preconcentration of trace Cu(II), Hg(II) and Pb(II) from water samples.

PubMed

Gao, Ru; Hu, Zheng; Chang, Xijun; He, Qun; Zhang, Lijun; Tu, Zhifeng; Shi, Jianping

2009-12-15

A new sorbent 1-acylthiosemicarbazide-modified activated carbon (AC-ATSC) was prepared as a solid-phase extractant and applied for removing of trace Cu(II), Hg(II) and Pb(II) prior to their determination by inductively coupled plasma optical emission spectrometry (ICP-OES). The separation/preconcentration conditions of analytes were investigated, including effects of pH, the shaking time, the sample flow rate and volume, the elution condition and the interfering ions. At pH 3, the maximum static adsorption capacity of Cu(II), Hg(II) and Pb(II) onto the AC-ATSC were 78.20, 67.80 and 48.56 mg g(-1), respectively. The adsorbed metal ions were quantitatively eluted by 3.0 mL of 2% CS(NH2)2 and 2.0 mol L(-1) HCl solution. Common coexisting ions did not interfere with the separation. According to the definition of IUPAC, the detection limits (3sigma) of this method for Cu(II), Hg(II) and Pb(II) were 0.20, 0.12 and 0.45 ng mL(-1), respectively. The relative standard deviation under optimum conditions is less than 4.0% (n=8). The prepared sorbent was applied for the preconcentration of trace Cu(II), Hg(II) and Pb(II) in certified and water samples with satisfactory results.
Angiotensin II up-regulates PAX2 oncogene expression and activity in prostate cancer via the angiotensin II type I receptor.

PubMed

Bose, Sudeep K; Gibson, Willietta; Giri, Shailendra; Nath, Narender; Donald, Carlton D

2009-09-01

Paired homeobox 2 gene (PAX2) is a transcriptional regulator, aberrantly expressed in prostate cancer cells and its down-regulation promotes cell death in these cells. The molecular mechanisms of tumor progression by PAX2 over-expression are still unclear. However, it has been reported that angiotensin-II (A-II) induces cell growth in prostate cancer via A-II type 1 receptor (AT1R) and is mediated by the phosphorylation of mitogen activated protein kinase (MAPK) as well as signal transducer and activator of transcription 3 (STAT3). Here we have demonstrated that A-II up-regulates PAX2 expression in prostate epithelial cells and prostate cancer cell lines resulting in increased cell growth. Furthermore, AT1R receptor antagonist losartan was shown to inhibit A-II induced PAX2 expression in prostate cancer. Moreover, analysis using pharmacological inhibitors against MEK1/2, ERK1/2, JAK-II, and phospho-STAT3 demonstrated that AT1R-mediated stimulatory effect of A-II on PAX2 expression was regulated in part by the phosphorylation of ERK1/2, JAK II, and STAT3 pathways. In addition, we have showed that down-regulation of PAX2 by an AT1R antagonist as well as JAK-II and STAT3 inhibitors suppress prostate cancer cell growth. Collectively, these findings show for the first time that the renin-angiotensin system (RAS) may promote prostate tumorigenesis via up-regulation of PAX2 expression. Therefore, PAX2 may be a novel therapeutic target for the treatment of carcinomas such as prostate cancer via the down-regulation of its expression by targeting the AT1R signaling pathways.
Application of calcium peroxide activated with Fe(II)-EDDS complex in trichloroethylene degradation.

PubMed

Zhang, Xiang; Gu, Xiaogang; Lu, Shuguang; Miao, Zhouwei; Xu, Minhui; Fu, Xiaori; Qiu, Zhaofu; Sui, Qian

2016-10-01

This study was conducted to assess the application of calcium peroxide (CP) activated with Fe(II) chelated by (S,S)-ethylenediamine-N,N'-disuccinic acid (EDDS) to enhance trichloroethylene (TCE) degradation in aqueous solution. It was indicated that EDDS prevented soluble iron from precipitation, and the optimum molar ratio of Fe(II)/EDDS to accelerate TCE degradation was 1/1. The influences of initial TCE, CP and Fe(II)-EDDS concentration were also investigated. The combination of CP and Fe(II)-EDDS complex rendered the efficient degradation of TCE at near neutral pH range. Chemical probe and scavenger tests identified that TCE degradation mainly owed to the oxidation of HO while O2(-) promoted HO generation. Cl(-), HCO3(-) and humic acid were found to inhibit CP/Fe(II)-EDDS performance on different levels. In conclusion, the application of CP activated with Fe(II)-EDDS complex is a promising technology in chemical remediation of groundwater, while further research in practical implementation is needed. Copyright © 2016 Elsevier Ltd. All rights reserved.
Zn(II)-Coordinated Quantum Dot-FRET Nanosensors for the Detection of Protein Kinase Activity.

PubMed

Lim, Butaek; Park, Ji-In; Lee, Kyung Jin; Lee, Jin-Won; Kim, Tae-Wuk; Kim, Young-Pil

2015-07-23

We report a simple detection of protein kinase activity using Zn(II)-mediated fluorescent resonance energy transfer (FRET) between quantum dots (QDs) and dye-tethered peptides. With neither complex chemical ligands nor surface modification of QDs, Zn(II) was the only metal ion that enabled the phosphorylated peptides to be strongly attached on the carboxyl groups of the QD surface via metal coordination, thus leading to a significant FRET efficiency. As a result, protein kinase activity in intermixed solution was efficiently detected by QD-FRET via Zn(II) coordination, especially when the peptide substrate was combined with affinity-based purification. We also found that mono- and di-phosphorylation in the peptide substrate could be discriminated by the Zn(II)-mediated QD-FRET. Our approach is expected to find applications for studying physiological function and signal transduction with respect to protein kinase activity.
Surface plasmon resonance spectroscopy studies of membrane proteins: transducin binding and activation by rhodopsin monitored in thin membrane films.

PubMed Central

Salamon, Z; Wang, Y; Soulages, J L; Brown, M F; Tollin, G

1996-01-01

Surface plasmon resonance (SPR) spectroscopy can provide useful information regarding average structural properties of membrane films supported on planar solid substrates. Here we have used SPR spectroscopy for the first time to monitor the binding and activation of G-protein (transducin or Gt) by bovine rhodopsin incorporated into an egg phosphatidylcholine bilayer deposited on a silver film. Rhodopsin incorporation into the membrane, performed by dilution of a detergent solution of the protein, proceeds in a saturable manner. Before photolysis, the SPR data show that Gt binds tightly (Keq approximately equal to 60 nM) and with positive cooperativity to rhodopsin in the lipid layer to form a closely packed film. A simple multilayer model yields a calculated average thickness of about 57 A, in good agreement with the structure of Gt. The data also demonstrate that Gt binding saturates at a Gt/rhodopsin ratio of approximately 0.6. Moreover, upon visible light irradiation, characteristic changes occur in the SPR spectrum, which can be modeled by a 6 A increase in the average thickness of the lipid/protein film caused by formation of metarhodopsin II (MII). Upon subsequent addition of GTP, further SPR spectral changes are induced. These are interpreted as resulting from dissociation of the alpha-subunit of Gt, formation of new MII-Gt complexes, and possible conformational changes of Gt as a consequence of complex formation. The above results clearly demonstrate the ability of SPR spectroscopy to monitor interactions among the proteins associated with signal transduction in membrane-bound systems. Images FIGURE 1 PMID:8804611
Peroxydisulfate activation by [RuII(tpy)(pic)(H2O)]+. Kinetic, mechanistic and anti-microbial activity studies.

PubMed

Chatterjee, Debabrata; Banerjee, Priyabrata; Bose, Jagadeesh C K; Mukhopadhyay, Sudit

2012-03-07

The oxidation of [Ru(II)(tpy)(pic)H(2)O](+) (tpy = 2,2',6',2''-terpyridine; pic(-) = picolinate) by peroxidisulfate (S(2)O(8)(2-)) as precursor oxidant has been investigated kinetically by UV-VIS, IR and EPR spectroscopy. The overall oxidation of Ru(II)- to Ru(IV)-species takes place in a consecutive manner involving oxidation of [Ru(II)(tpy)(pic)H(2)O](+) to [Ru(III)(tpy)(pic)(OH)](+), and its further oxidation of to the ultimate product [Ru(IV)(tpy)(pic)(O)](+) complex. The time course of the reaction was followed as a function of [S(2)O(8)(2-)], ionic strength (I) and temperature. Kinetic data and activation parameters are interpreted in terms of an outer-sphere electron transfer mechanism. Anti-microbial activity of Ru(II)(tpy)(pic)H(2)O](+) complex by inhibiting the growth of Escherichia coli DH5α in presence of peroxydisulfate has been explored, and the results of the biological studies have been discussed in terms of the [Ru(IV)(tpy)(pic)(O)](+) mediated cleavage of chromosomal DNA of the bacteria.
Cd(II) removal on surface-modified activated carbon: equilibrium, kinetics and mechanism.

PubMed

Liang, Jianjun; Liu, Meiling; Zhang, Yufei

2016-10-01

Commercial pulverous activated carbon (AC-0) was modified through two steps: oxidize AC-0 acid firstly, impregnate it with iron using ferric chloride secondly. Orthogonal experiment was conducted then to prepare modified activated carbon with high Cd(II) adsorption capacity (ACNF). Batch adsorption experiments were undertaken to determine the adsorption characteristics of Cd(II) from aqueous solution onto AC-0 and ACNF and the effect of pH, contact time and initial Cd(II) concentration. The results indicate that: the adsorption behavior of Cd(II) on ACNF can be well fitted with Langmuir model, and the maximum adsorption capacity of ACNF was 2.3 times higher than that of AC-0, supporting a monolayer coverage of Cd(II) on the surface. The kinetics of the adsorption process can be described by pseudo-second-order rate equation very well, and the adsorption capacity increased from 0.810 mg/g to 0.960 mg/g after modification. Compared with AC-0, the kinetic parameters of ACNF showed a higher adsorption rate through the aqueous solution to the solid surface and a lower intraparticle diffusion rate. Surface modification resulted in a lower Brunauer-Emmett-Teller (BET) surface area and pore size because of the collapse and blockage of pores, according to the X-ray diffraction (XRD) analysis, while the total number of surface oxygen acid groups increased, and this was supposed to contribute to the enhanced adsorption capacity of modified activated carbon.
Criminal Investigative Activities: World War II and Vietnam Battlefield Implications

DTIC Science & Technology

1988-06-03

WORLD WAR II AND VIET NAM BATTLEFIELD IMPLICATIONS •A thesis presented to the Faculty of the U. S. Army Command and General Staff College in partial...TIME COVERED 114. DATE OF REPORT (Year, Month, Day) 115. PAGE COUNT Master’s Thesis IFROM 8-1&~98 .TO..i-li38I 1988 June 3 I 145 16. SUPPLEMENTARY...CRIMINAL INVESTIGATIVE ACTIVITIES WORLD WAR II AND VIET NAM BATTLEFIELD !MPLICATIONS A thesis presented to the Faculty of the U. S. Army
Zn(II)-Coordinated Quantum Dot-FRET Nanosensors for the Detection of Protein Kinase Activity

PubMed Central

Lim, Butaek; Park, Ji-In; Lee, Kyung Jin; Lee, Jin-Won; Kim, Tae-Wuk; Kim, Young-Pil

2015-01-01

We report a simple detection of protein kinase activity using Zn(II)-mediated fluorescent resonance energy transfer (FRET) between quantum dots (QDs) and dye-tethered peptides. With neither complex chemical ligands nor surface modification of QDs, Zn(II) was the only metal ion that enabled the phosphorylated peptides to be strongly attached on the carboxyl groups of the QD surface via metal coordination, thus leading to a significant FRET efficiency. As a result, protein kinase activity in intermixed solution was efficiently detected by QD-FRET via Zn(II) coordination, especially when the peptide substrate was combined with affinity-based purification. We also found that mono- and di-phosphorylation in the peptide substrate could be discriminated by the Zn(II)-mediated QD-FRET. Our approach is expected to find applications for studying physiological function and signal transduction with respect to protein kinase activity. PMID:26213934
Calpain-10 Activity Underlies Angiotensin II-Induced Aldosterone Production in an Adrenal Glomerulosa Cell Model

PubMed Central

Seremwe, Mutsa; Schnellmann, Rick G.

2015-01-01

Aldosterone is a steroid hormone important in the regulation of blood pressure. Aberrant production of aldosterone results in the development and progression of diseases including hypertension and congestive heart failure; therefore, a complete understanding of aldosterone production is important for developing more effective treatments. Angiotensin II (AngII) regulates steroidogenesis, in part through its ability to increase intracellular calcium levels. Calcium can activate calpains, proteases classified as typical or atypical based on the presence or absence of penta-EF-hands, which are involved in various cellular responses. We hypothesized that calpain, in particular calpain-10, is activated by AngII in adrenal glomerulosa cells and underlies aldosterone production. Our studies showed that pan-calpain inhibitors reduced AngII-induced aldosterone production in 2 adrenal glomerulosa cell models, primary bovine zona glomerulosa and human adrenocortical carcinoma (HAC15) cells, as well as CYP11B2 expression in the HAC15 cells. Although AngII induced calpain activation in these cells, typical calpain inhibitors had no effect on AngII-elicited aldosterone production, suggesting a lack of involvement of classical calpains in this process. However, an inhibitor of the atypical calpain, calpain-10, decreased AngII-induced aldosterone production. Consistent with this result, small interfering RNA (siRNA)-mediated knockdown of calpain-10 inhibited aldosterone production and CYP11B2 expression, whereas adenovirus-mediated overexpression of calpain-10 resulted in increased AngII-induced aldosterone production. Our results indicate that AngII-induced activation of calpain-10 in glomerulosa cells underlies aldosterone production and identify calpain-10 or its downstream pathways as potential targets for the development of drug therapies for the treatment of hypertension. PMID:25836666
Selective activation of heparin cofactor II by a sulfated polysaccharide isolated from the leaves of Artemisia princeps.

PubMed

Hayakawa, Y; Hayashi, T; Hayashi, T; Niiya, K; Sakuragawa, N

1995-10-01

While checking anticoagulant activities in crude fractions from Wakan-Yakus (traditional herbal drugs), we detected antithrombin activity in the polysaccharide fraction of the leaves of Artemisia princeps Pamp. A sulfated polysaccharide purified from the crude fractions by ion-exchange chromatography on DEAE-cellulose and gel filtration on Sepharose 6B potentiated the heparin cofactor II (HC II)-dependent antithrombin activity but not the antithrombin activity of antithrombin III (AT III). The polysaccharide enhanced the HC II-thrombin reaction more than 6000-fold. The apparent second-order rate constant of thrombin inhibition by HC II increased from 3.8 x 10(4) (in the absence of the polysaccharide) to 2.5 x 10(8) M-1 min-1 in the presence of 25-125 micrograms/ml of the polysaccharide. In human plasma, the polysaccharide accelerated the formation of thrombin-HC II complex. The stimulating effect on HC II-dependent antithrombin activity was almost totally abolished by treatment with chondroitinase AC I, heparinase or heparitinase, while chondroitinase ABC or chondroitinase AC II had little or no effect. These results suggest that the polysaccharide is a glycosaminoglycan-like material with properties that are quite distinct from heparin or dermatan sulfate.
AT₁ receptor and NAD(P)H oxidase mediate angiotensin II-stimulated antioxidant enzymes and mitogen-activated protein kinase activity in the rat hypothalamus.

PubMed

Silva, José; Pastorello, Mariella; Arzola, Jorge; Zavala, Lida E; De Jesús, Sara; Varela, Maider; Matos, María Gabriela; del Rosario Garrido, María; Israel, Anita

2010-12-01

Angiotensin II (AngII) regulates blood pressure and water and electrolyte metabolism through the stimulation of NAD(P)H oxidase and production of reactive oxygen species (ROS) such as O₂⁻, which is metabolised by superoxide dismutase, catalase and glutathione peroxidase. We assessed the role of AT₁ and AT₂ receptors, NAD(P)H oxidase and protein kinase C (PKC) in Ang II-induced sodium and water excretion and their capacity to stimulate antioxidant enzymes in the rat hypothalamus, a brain structure known to express a high density of AngII receptors. Male Sprague-Dawley rats were intracerebroventricularly (ICV) injected with AngII and urinary sodium and water excretion was assessed. Urine sodium concentration was determined using flame photometry. After decapitation the hypothalamus was microdissected under stereomicroscopic control. Superoxide dismutase, catalase and glutathione peroxidase activity were determined spectrophotometrically and extracellular signal-regulated kinase (ERK1/2) activation was analysed by Western blot. AngII-ICV resulted in antidiuresis and natriuresis. ICV administration of losartan, PD123319, apocynin and chelerythrine blunted natriuresis. In hypothalamus, AngII increased catalase, superoxide dismutase and glutation peroxidase activity and ERK1/2 phosphorylation. These actions were prevented by losartan, apocynin and chelerythrine, and increased by PD123319. AT₁ and AT₂ receptors, NAD(P)H oxidase and PKC pathway are involved in the regulation of hydromineral metabolism and antioxidant enzyme activity induced by AngII.
p38 mitogen-activated protein kinase is involved in arginase-II-mediated eNOS-Uncoupling in Obesity

PubMed Central

2014-01-01

Background Endothelial nitric oxide synthase (eNOS)-uncoupling links obesity-associated insulin resistance and type-II diabetes to the increased incidence of cardiovascular disease. Studies have indicated that increased arginase is involved in eNOS-uncoupling through competing with the substrate L-arginine. Given that arginase-II (Arg-II) exerts some of its biological functions through crosstalk with signal transduction pathways, and that p38 mitogen-activated protein kinase (p38mapk) is involved in eNOS-uncoupling, we investigated here whether p38mapk is involved in Arg-II-mediated eNOS-uncoupling in a high fat diet (HFD)-induced obesity mouse model. Methods Obesity was induced in wild type (WT) and Arg-II-deficient (Arg-II-/-) mice on C57BL/6 J background by high-fat diet (HFD, 55% fat) for 14 weeks starting from age of 7 weeks. The entire aortas were isolated and subjected to 1) immunoblotting analysis of the protein level of eNOS, Arg-II and p38mapk activation; 2) arginase activity assay; 3) endothelium-dependent and independent vasomotor responses; 4) en face staining of superoxide anion and NO production with Dihydroethidium and 4,5-Diaminofluorescein Diacetate, respectively, to assess eNOS-uncoupling. To evaluate the role of p38mapk, isolated aortas were treated with p38mapk inhibitor SB203580 (10 μmol/L, 1 h) prior to the analysis. In addition, the role of p38mapk in Arg-II-induced eNOS-uncoupling was investigated in cultured human endothelial cells overexpressing Arg-II in the absence or presence of shRNA against p38mapk. Results HFD enhanced Arg-II expression/activity and p38mapk activity, which was associated with eNOS-uncoupling as revealed by decreased NO and enhanced L-NAME-inhibitable superoxide in aortas of WT obese mice. In accordance, WT obese mice revealed decreased endothelium-dependent relaxations to acetylcholine despite of higher eNOS protein level, whereas Arg-II-/- obese mice were protected from HFD-induced eNOS-uncoupling and
Synthesis, characterization and anti-microbial evaluation of Cu(II), Ni(II), Pt(II) and Pd(II) sulfonylhydrazone complexes; 2D-QSAR analysis of Ni(II) complexes of sulfonylhydrazone derivatives

NASA Astrophysics Data System (ADS)

Özbek, Neslihan; Alyar, Saliha; Alyar, Hamit; Şahin, Ertan; Karacan, Nurcan

2013-05-01

Copper(II), nickel(II), platinum(II) and palladium(II) complexes with 2-hydroxy-1-naphthaldehyde-N-methylpropanesulfonylhydrazone (nafpsmh) derived from propanesulfonic acid-1-methylhydrazide (psmh) were synthesized, their structure were identified, and antimicrobial activity of the compounds was screened against three Gram-positive and three Gram-negative bacteria. The results of antimicrobial studies indicate that Pt(II) and Pd(II) complexes showed the most activity against all bacteria. The crystal structure of 2-hydroxy-1-naphthaldehyde-N-methylpropanesulfonylhydrazone (nafpsmh) was also investigated by X-ray analysis. A series of Ni(II) sulfonyl hydrazone complexes (1-33) was synthesized and tested in vitro against Escherichia coli and Staphylococcus aureus. Their antimicrobial activities were used in the QSAR analysis. Four-parameter QSAR models revealed that nucleophilic reaction index for Ni and O atoms, and HOMO-LUMO energy gap play key roles in the antimicrobial activity.
Synthesis, spectroscopic characterization, DNA interaction and biological activities of Mn(II), Co(II), Ni(II) and Cu(II) complexes with [(1H-1,2,4-triazole-3-ylimino)methyl]naphthalene-2-ol

NASA Astrophysics Data System (ADS)

Gaber, Mohamed; El-Wakiel, Nadia A.; El-Ghamry, Hoda; Fathalla, Shaimaa K.

2014-11-01

Manganese(II), cobalt(II), nickel(II) and copper(II) complexes of [(1H-1,2,4-triazole-3-ylimino)methyl]naphthalene-2-ol have been synthesized. The structure of complexes have been characterized by elemental analysis, molar conductance, magnetic moment measurements and spectral (IR, 1H NMR, EI-mass, UV-Vis and ESR), and thermal studies. The results showed that the chloro and nitrato Cu(II) complexes have octahedral geometry while Ni(II), Co(II) and Mn(II) complexes in addition to acetato Cu(II) complex have tetrahedral geometry. The possible structures of the metal complexes have been computed using the molecular mechanic calculations using the hyper chem. 8.03 molecular modeling program to confirm the proposed structures. The kinetic and thermodynamic parameters of the thermal decomposition steps were calculated from the TG curves. The binding modes of the complexes with DNA have been investigated by UV-Vis absorption titration. The results showed that the mode of binding of the complexes to DNA is intercalative or non-intercalative binding modes. Schiff base and its metal complexes have been screened for their in vitro antimicrobial activities against Gram positive bacteria (Staphylococcus aureus), Gram negative bacteria (Escherichia coli and Pesudomonas aeruginosa), fungi (Asperigllus flavus and Mucer) and yeast (Candida albicans and Malassezia furfur).
Pharmacological Role of Anions (Sulphate, Nitrate, Oxalate and Acetate) on the Antibacterial Activity of Cobalt(II), Copper(II) and Nickel(II) Complexes With Nicotinoylhydrazine-Derived ONO, NNO and SNO Ligands

PubMed Central

Rauf, Abdur

1996-01-01

Mixed ligands biologically active complexes of cobalt(II), copper(II) and nickel(II) with nicotinoylhydrazine-derived ONO, NNO and SNO donor schiff-base ligands having the same metal ion but different anions such as sulphate, nitrate, oxalate and acetate have been synthesised and characterised on the basis of their physical, analytical and spectral data. In order to evaluate the role of anions on their bioability, these ligands and their synthesised metal complexes with various anions have been screened against bacterial species such as Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus and the title studies have proved a definative role of anions in increasing the biological activity PMID:18472896
Removal of zinc (II) ion from aqueous solution by adsorption onto activated palm midrib bio-sorbent

NASA Astrophysics Data System (ADS)

Mulana, F.; Mariana; Muslim, A.; Mohibah, M.; Halim, K. H. Ku

2018-03-01

In this paper, palm midrib that was activated with mixed citric acid and tartaric acid as biosorbent was used to remove Zn (II) ion from aqueous solution. The aim of this research is to activate palm midrib by using a mixed citric acid and tartaric acid and to determine adsorption capacity of activated palm midrib biosorbent on Zn (II) ion uptake from aqueous solution. The effect of several parameters such as contact time, initial Zn (II) ion concentration and activator concentration on the degree of Zn (II) ion removal was examined. Atomic Absorption Spectroscopy method was performed to determine adsorbed amount of Zn (II) ion into activated biosorbent. The result showed that the adsorption process was relatively not so fast and equilibrium was reached after contact time of 120 min. The adsorption capacity of biosorbent reached a maximum when the concentration of mixed citric acid and tartaric acid was 1.6 M. The optimum adsorption capacity was 5.72 mg/g. The result was obtained on initial Zn (II) ion concentration of 80 ppm for 120-min contact time. Langmuir isotherm was found as the best fit for the equilibrium data indicating homogeneous adsorption of metal ions onto the biosorbent surface.
Sticholysin II-mediated cytotoxicity involves the activation of regulated intracellular responses that anticipates cell death.

PubMed

Soto, Carmen; Bergado, Gretchen; Blanco, Rancés; Griñán, Tania; Rodríguez, Hermis; Ros, Uris; Pazos, Fabiola; Lanio, María Eliana; Hernández, Ana María; Álvarez, Carlos

2018-05-01

Sticholysin II (StII) is a pore-forming toxin of biomedical interest that belongs to the actinoporin protein family. Sticholysins are currently under examination as an active immunomodulating component of a vaccinal platform against tumoral cells and as a key element of a nucleic acids delivery system to cell cytosol. These proteins form pores in the plasma membrane leading to ion imbalance and cell lysis. However, the intracellular mechanisms triggered by actinoporins upon binding to membranes and its consequences for cell death are barely understood. Here, we have examined the cytotoxicity and intracellular responses induced by StII upon binding to human B-cell lymphoma Raji in vitro. StII cytotoxicity involves a functional actin cytoskeleton, induces cellular swelling, lysis and the concomitant release of cytosol content. In addition, StII induces calcium release mainly from the Endoplasmic Reticulum, activates Mitogen-Activated Protein Kinase ERK and impairs mitochondrial membrane potential. Furthermore, StII stimulates the expression of receptor interacting protein kinase 1 (RIP1), normally related to different forms of regulated cell death such as apoptosis and necroptosis. In correspondence, necrostatin-1, an inhibitor of this kinase, reduces StII cytotoxicity. However, the mechanism of cell death activated by StII does not involve caspases activation, typical molecular features of apoptosis and pyroptosis. Our results suggest that, beyond pore-formation and cell lysis, StII-induced cytotoxicity could involve other regulated intracellular mechanisms connected to RIP1-MEK1/2 -ERK1/2- pathways. This opens new perspectives and challenges the general point of view that these toxins induce a completely unregulated mechanism of necrotic cell death. This study contributes to a better understanding of the molecular mechanisms involved in toxin-cell interaction and the implications for cell functioning, with connotation for the exploitations of these toxins in
Synthesis, characterization and in vitro anticancer activity of 18-membered octaazamacrocyclic complexes of Co(II), Ni(II), Cd(II) and Sn(II)

NASA Astrophysics Data System (ADS)

Kareem, Abdul; Zafar, Hina; Sherwani, Asif; Mohammad, Owais; Khan, Tahir Ali

2014-10-01

An effective series of 18 membered octaazamacrocyclic complexes of the type [MLX2], where X = Cl or NO3 have been synthesized by template condensation reaction of oxalyl dihydrazide with dibenzoylmethane and metal salt in 2:2:1 molar ratio. The formation of macrocyclic framework, stereochemistry and their overall geometry have been characterized by various physico-chemical studies viz., elemental analysis, electron spray ionization-mass spectrometry (ESI-MS), I.R, UV-Vis, 1H NMR, 13C NMR spectroscopy, X-ray diffraction (XRD) and TGA/DTA studies. These studies suggest formation of octahedral macrocyclic complexes of Co(II), Ni(II), Cd(II) and Sn(II). The molar conductance values suggest nonelectrolytic nature for all the complexes. Thermogravimatric analysis shows that all the complexes are stable up to 600 °C. All these complexes have been tested against different human cancer cell lines i.e. human hepatocellular carcinoma (Hep3B), human cervical carcinoma (HeLa), human breast adenocarcinoma (MCF7) and normal cells (PBMC). The newly synthesized 18-membered octaazamacrocyclic complexes during in vitro anticancer evaluation, displayed moderate to good cytotoxicity on liver (Hep3B), cervical (HeLa) and breast (MCF7) cancer cell lines, respectively. The most effective anticancer cadmium complex (C34H28N10CdO10) was found to be active with IC50 values, 2.44 ± 1.500, 3.55 ± 1.600 and 4.82 ± 1.400 in micro-molar on liver, cervical and breast cancer cell lines, respectively.
Nickel(II) and palladium(II) triphenylphosphine complexes incorporating tridentate Schiff base ligands: Synthesis, characterization and biocidal activities

NASA Astrophysics Data System (ADS)

Shabbir, Muhammad; Akhter, Zareen; Ashraf, Ahmad Raza; Ismail, Hammad; Habib, Anum; Mirza, Bushra

2017-12-01

Nickel(II) and palladium(II) triphenylphosphine complexes incorporating tridentate Schiff bases have been prepared and characterized by elemental analysis as well as by spectroscopic techniques (FTIR & NMR). The synthesized compounds were assessed to check their potential biocidal activity by using different biological assays (brine shrimp cytotoxicity, antimicrobial, antioxidant, antitumor and drug-DNA interaction). Results of brine shrimp cytotoxicity assay showed that ligand molecules are more bioactive than metal complexes with LD50 as low as 12.4 μg/mL. The prominent antitumor activity was shown by nickel complexes while the palladium complexes exhibited moderate activity. The synthesized compounds have shown high propensity for DNA binding either through intercalation or groove binding which represents the mechanism of antitumor effect of these compounds. Additionally, ligand molecules and nickel metal complexes showed significant antioxidant activity with IC50 values as low as 3.1 μg/mL and 18.9 μg/mL respectively while palladium complexes exhibited moderate activity. Moreover, in antimicrobial assays H2L1, Ni(L1)PPh3 and H2L3 showed dual inhibition against bacterial and fungal strains while for the rest of the compounds varying degree of activity was recorded against different strains. Overall comparison of results suggests that the synthesized compounds can be promising candidate for drug formulation and development.

Modulation of CaM kinase II activity is coincident with induction of status epilepticus in the rat pilocarpine model.

PubMed

Singleton, Michael W; Holbert, William H; Lee, Anh Tuyet; Bracey, James M; Churn, Severn B

2005-09-01

This study was conducted to characterize the early cellular changes in CaM kinase II activity that occur during the induction of status epilepticus (SE). The pilocarpine model of SE was characterized both behaviorally and electrographically. At specific time points after the first discrete seizure, specific brain regions were isolated for biochemical study. Phosphate incorporation into a CaM kinase II-specific substrate, autocamtide III, was used to determine kinase activity. After the development of SE, the data show an immediate inhibition of both cortical and hippocampal CaM kinase II activity in homogenate, but a delayed inhibition in synaptic kinase activity. The maintenance of synaptic kinase activity was due to a translocation of CaM kinase II protein to the synapse. However, despite the translocation of functional kinase, CaM kinase II activity was not maintained, membrane potential was not restored, and the newly translocated CaM kinase II did not terminate the SE event. Unlike the homogenate samples, in the crude synaptoplasmic membrane (SPM) subcellular fractions, a positive correlation is found between the duration of SE and the inhibition of CaM kinase II activity in both the cortex and hippocampus. The data support the hypothesis that alterations of CaM kinase II activity are involved in the early events of SE pathology.
Design, synthesis, spectral characterization, DNA interaction and biological activity studies of copper(II), cobalt(II) and nickel(II) complexes of 6-amino benzothiazole derivatives

NASA Astrophysics Data System (ADS)

Daravath, Sreenu; Kumar, Marri Pradeep; Rambabu, Aveli; Vamsikrishna, Narendrula; Ganji, Nirmala; Shivaraj

2017-09-01

Two novel Schiff bases, L1 = (2-benzo[d]thiazol-6-ylimino)methyl)-4,6-dichlorophenol), L2 = (1-benzo[d]thiazol-6-ylimino)methyl)-6-bromo-4-chlorophenol) and their bivalent transition metal complexes [M(L1)2] and [M(L2)2], where M = Cu(II), Co(II) and Ni(II) were synthesized and characterized by elemental analysis, NMR, IR, UV-visible, mass, magnetic moments, ESR, TGA, SEM, EDX and powder XRD. Based on the experimental data a square planar geometry around the metal ion is assigned to all the complexes (1a-2c). The interaction of synthesized metal complexes with calf thymus DNA was explored using UV-visible absorption spectra, fluorescence and viscosity measurements. The experimental evidence indicated that all the metal complexes strongly bound to CT-DNA through an intercalation mode. DNA cleavage experiments of metal(II) complexes with supercoiled pBR322 DNA have also been explored by gel electrophoresis in the presence of H2O2 as well as UV light, and it is found that the Cu(II) complexes cleaved DNA more effectively compared to Co(II), Ni(II) complexes. In addition, the ligands and their metal complexes were screened for antimicrobial activity and it is found that all the metal complexes were more potent than free ligands.
A conserved carboxylic acid group mediates light-dependent proton uptake and signaling by rhodopsin.

PubMed

Arnis, S; Fahmy, K; Hofmann, K P; Sakmar, T P

1994-09-30

A carboxylic acid residue is conserved at the cytoplasmic border of the third transmembrane segment among nearly all G protein-coupled receptors. In the visual receptor rhodopsin, replacement of the conserved Glu134 by a neutral glutamine results in enhanced transducin activation. Here we show that a key event in forming the active state of rhodopsin is proton uptake by Glu134 in the metarhodopsin II (MII) photoproduct. Site-directed mutants E134D and E134Q were studied by flash photolysis, where formation rates of their photoproducts and rates of pH change could be monitored simultaneously. Both mutants showed normal MII formation rates. However, E134D displayed a slowed rate of proton uptake and E134Q displayed a loss of light-induced uptake of two protons from the aqueous phase. Thus, Glu134 mediates light-dependent proton uptake by MII. We propose that receptor activation requires a light-induced conformational change that allows protonation of Glu134 and subsequent protonation of a second group. The strong conservation of Glu134 in G protein-coupled receptors implies a general requirement for a proton acceptor group at this position to allow light- or ligand-dependent receptor activation.
Learning Activity Packets for Auto Mechanics II. Section A--Engine Rebuilding.

ERIC Educational Resources Information Center

Oklahoma State Board of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

Eight learning activity packets (LAPs) are provided for the instructional area of engine rebuilding in the auto mechanics II program. They accompany an instructor's guide available separately. The LAPs outline the study activities and performance tasks for these eight units: (1) engine condition evaluation; (2) engine removal; (3) engine…
Anticonvulsant activity of DNS II fraction in the acute seizure models.

PubMed

Raza, Muhammad Liaquat; Zeeshan, Mohammad; Ahmad, Manzoor; Shaheen, Farzana; Simjee, Shabana U

2010-04-21

Delphinium nordhagenii belongs to family Ranunculaceae, it is widely found in tropical areas of Pakistan. Other species of Delphinium are reported as anticonvulsant and are traditionally used in the treatment of epilepsy. Delphinium nordhagenii is used by local healer in Pakistan but never used for scientific investigation as anticonvulsant. Thus, Delphinium nordhagenii was subjected to bioassay-guided fractionation and the most active fraction, i.e. DNS II acetone was chosen for further testing in the acute seizure models of epilepsy to study the antiepileptic potential in male mice. Different doses (60, 65 and 70mg/kg, i.p.) of DNS II acetone fraction of Delphinium nordhagenii was administered 30min prior the chemoconvulsant's injection in the male mice. Convulsive doses of chemoconvulsants (pentylenetetrazole 90mg/kg, s.c. and picrotoxin 3.15mg/kg, s.c.) were used. The mice were observed 45-90min for the presence of seizures. Moreover, four different doses of DNS II (60, 65, 70 and 100mg/kg, i.p.) were tested in the MES test. The DNS II acetone fraction of Delphinium nordhagenii has exhibited the anticonvulsant actions by preventing the seizures against PTZ- and picrotoxin-induced seizure as well as 100% seizure protection in MES test. The results are comparable with standard AEDs (diazepam 7.5mg/kg, i.p. and phenytoin 20mg/kg, i.p.). These findings suggest that the Delphinium nordhagenii possesses the anticonvulsant activity. Further analysis is needed to confirm the structure and target the extended activity profile. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
Carbonic anhydrase activators. Activation of isoforms I, II, IV, VA, VII, and XIV with L- and D-phenylalanine and crystallographic analysis of their adducts with isozyme II: stereospecific recognition within the active site of an enzyme and its consequences for the drug design.

PubMed

Temperini, Claudia; Scozzafava, Andrea; Vullo, Daniela; Supuran, Claudiu T

2006-05-18

Activation of six human brain carbonic anhydrases (hCAs, EC 4.2.1.1), hCA I, II, IV, VA, VII, and XIV, with l-/d-phenylalanine was investigated kinetically and by X-ray crystallography. l-Phe was a potent activator of isozymes I, II, and XIV (K(A)s of 13-240 nM), a weaker activator of hCA VA and VII (K(A)s of 9.8-10.9 microM), and a quite inefficient hCA IV activator (K(A) of 52 microM). d-Phe showed good hCA II activatory properties (K(A) of 35 nM), being a moderate hCA VA, VII, and XIV (K(A)s of 4.6-9.7 microM) and a weak hCA I and IV activator (K(A)s of 63-86 microM). X-ray crystallography of the hCA II-l-Phe/d-Phe adducts showed the activators to be anchored at the entrance of the active site, participating in numerous bonds and hydrophobic interactions with amino acid residues His64, Thr200, Trp5, and Pro201. This is the first study showing different binding modes of stereoisomeric activators within the hCA II active site, with consequences for overall proton transfer processes (rate-determining for the catalytic cycle). It also points out differences of activation efficiency between various isozymes with structurally related activators, exploitable for designing alternative proton transfer pathways. CA activators may lead to the design of pharmacologically useful derivatives for the enhancement of synaptic efficacy, which may represent a conceptually new approach for the treatment of Alzheimer's disease, aging, and other conditions in which spatial learning and memory therapy must be enhanced. As the blood and brain concentrations of l-Phe are quite variable (30-73 microM), activity of some brain CAs may strongly be influenced by the level of activator(s) present in such tissues.
Effect of endogenous angiotensin II on renal nerve activity and its cardiac baroreflex regulation.

PubMed

Dibona, G F; Jones, S Y; Sawin, L L

1998-11-01

The effects of physiologic alterations in endogenous angiotensin II activity on basal renal sympathetic nerve activity and its cardiac baroreflex regulation were studied. The effect of angiotensin II type 1 receptor blockade with intracerebroventricular losartan was examined in conscious rats consuming a low, normal, or high sodium diet that were instrumented for the simultaneous measurement of right atrial pressure and renal sympathetic nerve activity. The gain of cardiac baroreflex regulation of renal sympathetic nerve activity (% delta renal sympathetic nerve activity/mmHg mean right atrial pressure) was measured during isotonic saline volume loading. Intracerebroventricular losartan did not decrease arterial pressure but significantly decreased renal sympathetic nerve activity in low (-36+/-6%) and normal (-24+/-5%), but not in high (-2+/-3%) sodium diet rats. Compared with vehicle treatment, losartan treatment significantly increased cardiac baroreflex gain in low (-3.45+/-0.20 versus -2.89+/-0.17) and normal (-2.89+/-0.18 versus -2.54+/-0.14), but not in high (-2.27+/-0.15 versus -2.22+/-0.14) sodium diet rats. These results indicate that physiologic alterations in endogenous angiotensin II activity tonically influence basal levels of renal sympathetic nerve activity and its cardiac baroreflex regulation.
DNA Binding and Antitumor Activity of α-Diimineplatinum(II) and Palladium(II) Dithiocarbamate Complexes

PubMed Central

Mansouri-Torshizi, Hassan; Saeidifar, Maryam; Khosravi, Fatemeh; Divsalar, Adeleh; Saboury, Ali Akbar; Hassani, Fatemeh

2011-01-01

The two water-soluble designed platinum(II) complex, [Pt(Oct-dtc)(bpy)]NO3 (Oct-dtc = Octyldithiocarbamate and bpy = 2,2′ -bipyridine) and palladium(II) complex, [Pd(Oct-dtc)(bpy)]NO3, have been synthesized and characterized by elemental analyses, molar conductivity measurements, IR, 1H NMR, and electronic spectra studies. Studies of antitumor activity of these complexes against human cell tumor lines (K562) have been carried out. They show Ic50 values lower than that of cisplatin. The complexes have been investigated for their interaction with calf thymus DNA (CT-DNA) by utilizing the electronic absorption spectroscopy, fluorescence spectra, and ethidium bromide displacement and gel filtration techniques. Both of these water-soluble complexes bound cooperatively and intercalatively to the CT-DNA at very low concentrations. Several binding and thermodynamic parameters are also described. PMID:22110410
Modulation of GABAergic receptor binding by activation of calcium and calmodulin-dependent kinase II membrane phosphorylation.

PubMed

Churn, S B; DeLorenzo, R J

1998-10-26

gamma-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system (CNS). Because of the important role that GABA plays in the CNS, alteration of GABAA receptor function would significantly affect neuronal excitability. Protein phosphorylation is a major mechanism for regulating receptor function in the brain and has been implicated in modulating GABAA receptor function. Therefore, this study was initiated to determine the role of calmodulin-dependent kinase II (CaM kinase II) membrane phosphorylation on GABAA receptor binding. Synaptosomal membrane fractions were tested for CaM kinase II activity towards endogenous substrates. In addition, muscimol binding was evaluated under equilibrium conditions in synaptosomal membrane fractions subjected to either basal (Mg2+ alone) or maximal CaM kinase II-dependent phosphorylation. Activation of endogenous CaM kinase II-dependent phosphorylation resulted in a significant enhancement of the apparent Bmax for muscimol binding without significantly altering the apparent binding affinity. The enhanced muscimol binding could be increased further by the addition of exogenous CaM kinase II to synaptosomal membrane fractions. Co-incubation with inhibitors of kinase activity during the phosphorylation reactions blocked the CaM kinase II-dependent increase in muscimol binding. The data support the hypothesis that activation of CaM kinase II-dependent phosphorylation caused an increased GABAA receptor binding and may play an important role in modulating the function of this inhibitory receptor/chloride ion channel complex. Copyright 1998 Elsevier Science B.V.
Rapid detection of protein phosphatase activity using Zn(II)-coordinated gold nanosensors based on His-tagged phosphopeptides.

PubMed

Lee, Jin Oh; Kim, Eun-Ji; Lim, Butaek; Kim, Tae-Wuk; Kim, Young-Pil

2015-01-20

We report a rapid colorimetric assay to detect protein phosphatase (PP) activity based on the controlled assembly and disassembly of gold nanoparticles (AuNPs) via Zn(II)-specific coordination in the presence of His6-tagged phosphopeptides. Among divalent metal ions including Ni(II), Cu(II), Co(II), Mg(II), Mn(II), and Zn(II), only Zn(II) triggered a strong association between phosphopeptides with hexahistidine at a single end and nitrilotriacetic acid (NTA)-modified AuNPs (21.3 nm in core diameter), leading to the self-assembly of AuNPs and consequently changes in color of the AuNP solution. In contrast, unphosphorylated peptides and His6-deficient phosphopeptides did not change the color of the AuNP solution. As a result, protein phosphatase 1 (PP1) activity and its inhibition were easily quantified with high sensitivity by determining the extinction ratio (E520/E700) of colloidal AuNPs. Most importantly, this method was capable of detecting protein phosphatase 2A (PP2A) activity in immunoprecipitated plant extracts. Because PPs play pivotal roles in mediating diverse signal transduction pathways as primary effectors of protein dephosphorylation, we anticipate that our method will be applied as a rapid format method to analyze the activities of various PPs and their inhibition.
Learning Activity Packets for Auto Mechanics II. Section B--Electrical Systems.

ERIC Educational Resources Information Center

Oklahoma State Board of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

Six learning activity packets (LAPs) are provided for the instructional area of electrical systems in the auto mechanics II program. They accompany an instructor's guide available separately. The LAPs outline the study activities and performance tasks for these six units: (1) basic electrical theory, (2) battery service, (3) starting system, (4)…
Mitogen-activated protein kinase is required for the behavioral desensitization that occurs after repeated injections of angiotensin II

PubMed Central

Vento, Peter J.; Daniels, Derek

2013-01-01

Angiotensin II (AngII) acts on central angiotensin type 1 (AT1) receptors to increase water and saline intake. Prolonged exposure to AngII in cell culture models results in a desensitization of the AT1 receptor that is thought to involve receptor internalization, and a behavioral correlate of this desensitization has been shown in rats after repeated central injections of AngII. Specifically, rats given repeated injections of AngII drink less water than controls after a subsequent test injection of AngII. Under the same conditions, however, repeated injections of AngII have no effect on AngII-induced saline intake. Given earlier studies indicating that separate intracellular signaling pathways mediate AngII-induced water and saline intake, we hypothesized that the desensitization observed in rats may be incomplete, leaving the receptor able to activate mitogen-activated protein (MAP) kinases (ERK1/2), which play a role in AngII-induced saline intake without affecting water intake. In support of this hypothesis, we found no difference in MAP kinase phosphorylation after an AngII test injection in rats given prior treatment with repeated injections of vehicle, AngII, or Sar1,Ile4,Ile8-AngII (SII), an AngII analog that activates MAP kinase without G protein coupling. In addition, we found that pretreatment with the MAP kinase inhibitor U0126 completely blocked the desensitizing effect of repeated AngII injections on water intake. Furthermore, AngII-induced water intake was reduced similarly by repeated injections of AngII or SII. The results suggest that G protein-independent signaling is sufficient to produce behavioral desensitization of the angiotensin system and that the desensitization requires MAP kinase activation. PMID:22581747
Mitogen-activated protein kinase is required for the behavioural desensitization that occurs after repeated injections of angiotensin II.

PubMed

Vento, Peter J; Daniels, Derek

2012-12-01

Angiotensin II (Ang II) acts on central angiotensin type 1 (AT(1)) receptors to increase water and saline intake. Prolonged exposure to Ang II in cell culture models results in a desensitization of the AT(1) receptor that is thought to involve receptor internalization, and a behavioural correlate of this desensitization has been shown in rats after repeated central injections of Ang II. Specifically, rats given repeated injections of Ang II drink less water than control animals after a subsequent test injection of Ang II. In the same conditions, however, repeated injections of Ang II have no effect on Ang II-induced saline intake. Given earlier studies indicating that separate intracellular signalling pathways mediate Ang II-induced water and saline intake, we hypothesized that the desensitization observed in rats may be incomplete, leaving the receptor able to activate mitogen-activated protein (MAP) kinases (ERK1/2), which play a role in Ang II-induced saline intake without affecting water intake. In support of this hypothesis, we found no difference in MAP kinase phosphorylation after an Ang II test injection in rats given prior treatment with repeated injections of vehicle, Ang II or Sar(1),Ile(4),Ile(8)-Ang II (SII), an Ang II analogue that activates MAP kinase without G protein coupling. In addition, we found that pretreatment with the MAP kinase inhibitor U0126 completely blocked the desensitizing effect of repeated Ang II injections on water intake. Furthermore, Ang II-induced water intake was reduced to a similar extent by repeated injections of Ang II or SII. The results suggest that G protein-independent signalling is sufficient to produce behavioural desensitization of the angiotensin system and that the desensitization requires MAP kinase activation.
Mercury (II) removal by resistant bacterial isolates and mercuric (II) reductase activity in a new strain of Pseudomonas sp. B50A.

PubMed

Giovanella, Patricia; Cabral, Lucélia; Bento, Fátima Menezes; Gianello, Clesio; Camargo, Flávio Anastácio Oliveira

2016-01-25

This study aimed to isolate mercury resistant bacteria, determine the minimum inhibitory concentration for Hg, estimate mercury removal by selected isolates, explore the mer genes, and detect and characterize the activity of the enzyme mercuric (II) reductase produced by a new strain of Pseudomonas sp. B50A. The Hg removal capacity of the isolates was determined by incubating the isolates in Luria Bertani broth and the remaining mercury quantified by atomic absorption spectrophotometry. A PCR reaction was carried out to detect the merA gene and the mercury (II) reductase activity was determined in a spectrophotometer at 340 nm. Eight Gram-negative bacterial isolates were resistant to high mercury concentrations and capable of removing mercury, and of these, five were positive for the gene merA. The isolate Pseudomonas sp. B50A removed 86% of the mercury present in the culture medium and was chosen for further analysis of its enzyme activity. Mercuric (II) reductase activity was detected in the crude extract of this strain. This enzyme showed optimal activity at pH 8 and at temperatures between 37 °C and 45 °C. The ions NH4(+), Ba(2+), Sn(2+), Ni(2+) and Cd(2+) neither inhibited nor stimulated the enzyme activity but it decreased in the presence of the ions Ca(2+), Cu(+) and K(+). The isolate and the enzyme detected were effective in reducing Hg(II) to Hg(0), showing the potential to develop bioremediation technologies and processes to clean-up the environment and waste contaminated with mercury. Copyright © 2015 Elsevier B.V. All rights reserved.
Structure of the Ni(II) complex of Escherichia coli peptide deformylase and suggestions on deformylase activities depending on different metal(II) centres.

PubMed

Yen, Ngo Thi Hai; Bogdanović, Xenia; Palm, Gottfried J; Kühl, Olaf; Hinrichs, Winfried

2010-02-01

Crystal structures of polypeptide deformylase (PDF) of Escherichia coli with nickel(II) replacing the native iron(II) have been solved with chloride and formate as metal ligands. The chloro complex is a model for the correct protonation state of the hydrolytic hydroxo ligand and the protonated status of the Glu133 side chain as part of the hydrolytic mechanism. The ambiguity that recently some PDFs have been identified with Zn(2+) ion as the active-site centre whereas others are only active with Fe(2+) (or Co(2+), Ni(2+) is discussed with respect to Lewis acid criteria of the metal ion and substrate activation by the CD loop.
Synthesis, characterization, antimicrobial activity and carbonic anhydrase enzyme inhibitor effects of salicilaldehyde-N-methyl p-toluenesulfonylhydrazone and its Palladium(II), Cobalt(II) complexes

NASA Astrophysics Data System (ADS)

Alyar, Saliha; Adem, Şevki

2014-10-01

We report the synthesis of the ligand, salicilaldehyde-N-methyl p-toluenesulfonylhydrazone (salptsmh) derived from p-toluenesulfonicacid-1-methylhydrazide (ptsmh) and its Pd(II) and Co(II) metal complexes were synthesized for the first time. The structure of the ligand and their complexes were investigated using elemental analysis, magnetic susceptibility, molar conductance and spectral (IR, NMR and LC-MS) measurements. Salptsmh has also been characterized by single crystal X-ray diffraction. 1H and 13C shielding tensors for crystal structure were calculated with GIAO/DFT/B3LYP/6-311++G(d,p) methods in CDCl3. The complexes were found to have general composition [ML2]. The results of elemental analysis showed 1:2 (metal/ligand) stoichiometry for all the complex. Magnetic and spectral data indicate a square planar geometry for Pd(II) complex and a distorted tetrahedral geometry for Co(II) complexes. The ligand and its metal chelates have been screened for their antimicrobial activities using the disk diffusion method against the selected Gram positive bacteria: Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, Enterococcus faecalis, Gram negative bacteria: Eschericha coli, Pseudomonas aeruginosa, Klebsiella pneumonia. The inhibition activities of these compounds on carbonic anhydrase II (CA II) and carbonic anhydrase I (CA I) have been investigated by comparing IC50 and Ki values and it has been found that Pd(II) complex have more enzyme inhibition efficiency than salptsmh and Co(II) complex.
77 FR 60124 - Draft Guidance for Industry on Initial Completeness Assessments for Type II Active Pharmaceutical...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1010] Draft Guidance for Industry on Initial Completeness Assessments for Type II Active Pharmaceutical... certain drug master files, namely, Type II active pharmaceutical ingredient (API) drug master files (DMFs...
Application of EDTA-functionalized bamboo activated carbon (BAC) for Pb(II) and Cu(II) removal from aqueous solutions

NASA Astrophysics Data System (ADS)

Lv, Dan; Liu, Yu; Zhou, Jiasheng; Yang, Kunlun; Lou, Zimo; Baig, Shams Ali; Xu, Xinhua

2018-01-01

In this study, a novel bamboo activated carbon (BAC) with ethylene diamine tetraacetic acid (EDTA) functionality was prepared by direct grafting in the presence of tetraethyl orthosilicate (TEOS) as a crosslinking agent. The BAC@SiO2-EDTA was characterized by SEM, TEM, TGA, FTIR, XPS and its adsorption property for removal of Pb(II) and Cu(II) under various experimental conditions was also investigated. The characterization results reflected that EDTA was successfully assembled on the surface of the BAC and average pore size increased from 4.10 to 4.83 nm as BAC grafted with EDTA. Adsorption data fitted very well in Langmuir isotherm model and pseudo-second-order kinetic model. As compared with the raw BAC, the maximum adsorption capacities of BAC@SiO2-EDTA for the Pb(II) and Cu(II) increased from 45.45 to 123.45 mg g-1 and from 6.85 to 42.19 mg g-1, since the existence of EDTA on modified BAC promoted the formation of chemical complex. The removal of heavy metal ions mainly depended on the complexation with EDTA and the electrostatic attractions with negatively charged surface of BAC@SiO2-EDTA. The adsorption of Pb(II)/Cu(II) on the BAC@SiO2-EDTA was pH dependent and pH 5-6 was considered an optimum. However, lower temperature favored the adsorption and the maximum adsorption was recorded at 20 °C. In addition, BAC@SiO2-EDTA had an excellent reusability with about 40% decline in the adsorption capacity for Pb(II) after fifth reuse. Insignificant influences of co-existing cations and natural organic matter (NOM) were found on the adsorption of Pb(II) and Cu(II). All the results demonstrate that BAC@SiO2-EDTA is a potential adsorbent for metal ions in wastewater.
Genotype-dependent activation or repression of HBV enhancer II by transcription factor COUP-TF1

PubMed Central

Fischer, Silke F; Schmidt, Katja; Fiedler, Nicola; Glebe, Dieter; Schüttler, Christian; Sun, Jianguang; Gerlich, Wolfram H; Repp, Reinald; Schaefer, Stephan

2006-01-01

AIM: To study the expression of HBV enhancer II by transcription factor COUP-TF1. METHODS: In order to study the regulation of HBV variants in the vicinity of the NRRE we cloned luciferase constructs containing the HBV enhancer II from variants and from HBV genotypes A and D and cotransfected them together with expression vectors for COUP-TF1 into HepG2 cells. RESULTS: Our findings show that enhancer II of HBV genotype A is also repressed by COUP-TF1. In contrast, two different enhancer II constructs of HBV genotype D were activated by COUP-TF1. The activation was independent of the NRRE because a natural variant with a deletion of nt 1763-1770 was still activated by COUP-TF1. CONCLUSION: Regulation of transcription of the HBV genome seems to differ among HBV genomes derived from different genotypes. These differences in transcriptional control among HBV genotypes may be the molecular basis for differences in the clinical course among HBV genotypes. PMID:17009409
Genotype-dependent activation or repression of HBV enhancer II by transcription factor COUP-TF1.

PubMed

Fischer, Silke F; Schmidt, Katja; Fiedler, Nicola; Glebe, Dieter; Schüttler, Christian; Sun, Jianguang; Gerlich, Wolfram H; Repp, Reinald; Schaefer, Stephan

2006-10-07

To study the expression of HBV enhancer II by transcription factor COUP-TF1. In order to study the regulation of HBV variants in the vicinity of the NRRE we cloned luciferase constructs containing the HBV enhancer II from variants and from HBV genotypes A and D and cotransfected them together with expression vectors for COUP-TF1 into HepG2 cells. Our findings show that enhancer II of HBV genotype A is also repressed by COUP-TF1. In contrast, two different enhancer II constructs of HBV genotype D were activated by COUP-TF1. The activation was independent of the NRRE because a natural variant with a deletion of nt 1763-1770 was still activated by COUP-TF1. Regulation of transcription of the HBV genome seems to differ among HBV genomes derived from different genotypes. These differences in transcriptional control among HBV genotypes may be the molecular basis for differences in the clinical course among HBV genotypes.

Activity of phosphino palladium(II) and platinum(II) complexes against HIV-1 and Mycobacterium tuberculosis.

PubMed

Gama, Ntombenhle H; Elkhadir, Afag Y F; Gordhan, Bhavna G; Kana, Bavesh D; Darkwa, James; Meyer, Debra

2016-08-01

Treatment of human immunodeficiency virus (HIV) is currently complicated by increased prevalence of co-infection with Mycobacterium tuberculosis. The development of drug candidates that offer the simultaneous management of HIV and tuberculosis (TB) would be of great benefit in the holistic treatment of HIV/AIDS, especially in sub-Saharan Africa which has the highest global prevalence of HIV-TB coinfection. Bis(diphenylphosphino)-2-pyridylpalladium(II) chloride (1), bis(diphenylphosphino)-2-pyridylplatinum(II) chloride (2), bis(diphenylphosphino)-2-ethylpyridylpalladium(II) chloride (3) and bis(diphenylphosphino)-2-ethylpyridylplatinum(II) (4) were investigated for the inhibition of HIV-1 through interactions with the viral protease. The complexes were subsequently assessed for biological potency against Mycobacterium tuberculosis H37Rv by determining the minimal inhibitory concentration (MIC) using broth microdilution. Complex (3) showed the most significant and competitive inhibition of HIV-1 protease (p = 0.014 at 100 µM). Further studies on its in vitro effects on whole virus showed reduced viral infectivity by over 80 % at 63 µM (p < 0.05). In addition, the complex inhibited the growth of Mycobacterium tuberculosis at an MIC of 5 µM and was non-toxic to host cells at all active concentrations (assessed by tetrazolium dye and real time cell electronic sensing). In vitro evidence is provided here for the possibility of utilizing a single metal-based compound for the treatment of HIV/AIDS and TB.
Removal of lead (II) ions from aqueous solutions onto activated carbon derived from waste biomass.

PubMed

Erdem, Murat; Ucar, Suat; Karagöz, Selhan; Tay, Turgay

2013-01-01

The removal of lead (II) ions from aqueous solutions was carried out using an activated carbon prepared from a waste biomass. The effects of various parameters such as pH, contact time, initial concentration of lead (II) ions, and temperature on the adsorption process were investigated. Energy Dispersive X-Ray Spectroscopy (EDS) analysis after adsorption reveals the accumulation of lead (II) ions onto activated carbon. The Langmuir and Freundlich isotherm models were applied to analyze equilibrium data. The maximum monolayer adsorption capacity of activated carbon was found to be 476.2 mg g⁻¹. The kinetic data were evaluated and the pseudo-second-order equation provided the best correlation. Thermodynamic parameters suggest that the adsorption process is endothermic and spontaneous.
RNA polymerase II pausing can be retained or acquired during activation of genes involved in the epithelial to mesenchymal transition

PubMed Central

Samarakkody, Ann; Abbas, Ata; Scheidegger, Adam; Warns, Jessica; Nnoli, Oscar; Jokinen, Bradley; Zarns, Kris; Kubat, Brooke; Dhasarathy, Archana; Nechaev, Sergei

2015-01-01

Promoter-proximal RNA polymerase II (Pol II) pausing is implicated in the regulation of gene transcription. However, the mechanisms of pausing including its dynamics during transcriptional responses remain to be fully understood. We performed global analysis of short capped RNAs and Pol II Chromatin Immunoprecipitation sequencing in MCF-7 breast cancer cells to map Pol II pausing across the genome, and used permanganate footprinting to specifically follow pausing during transcriptional activation of several genes involved in the epithelial to mesenchymal transition (EMT). We find that the gene for EMT master regulator Snail (SNAI1), but not Slug (SNAI2), shows evidence of Pol II pausing before activation. Transcriptional activation of the paused SNAI1 gene is accompanied by a further increase in Pol II pausing signal, whereas activation of non-paused SNAI2 gene results in the acquisition of a typical pausing signature. The increase in pausing signal reflects increased transcription initiation without changes in Pol II pausing. Activation of the heat shock HSP70 gene involves pausing release that speeds up Pol II turnover, but does not change pausing location. We suggest that Pol II pausing is retained during transcriptional activation and can further undergo regulated release in a signal-specific manner. PMID:25820424
Staphylococcus-mediated T-cell activation and spontaneous natural killer cell activity in the absence of major histocompatibility complex class II molecules

NASA Technical Reports Server (NTRS)

Chapes, S. K.; Hoynowski, S. M.; Woods, K. M.; Armstrong, J. W.; Beharka, A. A.; Iandolo, J. J.; Spooner, B. S. (Principal Investigator)

1993-01-01

We used major histocompatibility complex class II antigen-deficient transgenic mice to show that in vitro natural killer cell cytotoxicity and T-cell activation by staphylococcal exotoxins (superantigens) are not dependent upon the presence of major histocompatibility complex class II molecules. T cells can be activated by exotoxins in the presence of exogenously added interleukin 1 or 2 or in the presence of specific antibody without exogenously added cytokines.
DNA/RNA binding and anticancer/antimicrobial activities of polymer-copper(II) complexes

NASA Astrophysics Data System (ADS)

Lakshmipraba, Jagadeesan; Arunachalam, Sankaralingam; Riyasdeen, Anvarbatcha; Dhivya, Rajakumar; Vignesh, Sivanandham; Akbarsha, Mohammad Abdulkader; James, Rathinam Arthur

2013-05-01

Water soluble polymer-copper(II) complexes with various degrees of coordination in the polymer chain were synthesized and characterized by elemental analysis, IR, UV-visible and EPR spectra. The DNA/RNA binding behavior of these polymer-copper(II) complexes was examined by UV-visible absorption, emission and circular dichroism spectroscopic methods, and cyclic voltammetry techniques. The binding of the polymer-copper(II) complexes with DNA/RNA was mainly through intercalation but some amount of electrostatic interaction was also observed. This binding capacity increased with the degree of coordination of the complexes. The polymer-copper(II) complex having the highest degree of coordination was subjected to analysis of cytotoxic and antimicrobial properties. The cytotoxicity study indicated that the polymer-copper(II) complexes affected the viability of MCF-7 mammary carcinoma cells, and the cells responded to the treatment with mostly through apoptosis although a few cells succumbed to necrosis. The antimicrobial screening showed activity against some human pathogens.
Architecture of the Yeast RNA Polymerase II Open Complex and Regulation of Activity by TFIIF

PubMed Central

Fishburn, James

2012-01-01

To investigate the function and architecture of the open complex state of RNA polymerase II (Pol II), Saccharomyces cerevisiae minimal open complexes were assembled by using a series of heteroduplex HIS4 promoters, TATA binding protein (TBP), TFIIB, and Pol II. The yeast system demonstrates great flexibility in the position of active open complexes, spanning 30 to 80 bp downstream from TATA, consistent with the transcription start site scanning behavior of yeast Pol II. TFIIF unexpectedly modulates the activity of the open complexes, either repressing or stimulating initiation. The response to TFIIF was dependent on the sequence of the template strand within the single-stranded bubble. Mutations in the TFIIB reader and linker region, which were inactive on duplex DNA, were suppressed by the heteroduplex templates, showing that a major function of the TFIIB reader and linker is in the initiation or stabilization of single-stranded DNA. Probing of the architecture of the minimal open complexes with TFIIB-FeBABE [TFIIB–p-bromoacetamidobenzyl–EDTA-iron(III)] derivatives showed that the TFIIB core domain is surprisingly positioned away from Pol II, and the addition of TFIIF repositions the TFIIB core domain to the Pol II wall domain. Together, our results show an unexpected architecture of minimal open complexes and the regulation of activity by TFIIF and the TFIIB core domain. PMID:22025674
Synthesis, characterization and anti-microbial activity of phenylurea-formaldehyde resin (PUF) and its polymer metal complexes (PUF-Mn(II)

NASA Astrophysics Data System (ADS)

Ahamad, Tansir; Alshehri, Saad M.

2012-10-01

Phenylurea-formaldehyde polymer (PUF) was synthesized via polycondensation of phenylurea and formaldehyde in basic medium, its polymer-metal complexes [PUF-M(II)] were prepared with Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) ions. PUF and PUF-M(II) were characterized with magnetic moment measurements, elemental and spectral (UV-visible, FTIR, 1H-NMR, 13C-NMR and ESR) analysis. The thermal behaviors of all the synthesized polymers were carried out using thermogravimetric analysis (TGA) and differential thermal analysis (DTA). The thermal data revealed that all of the PUF-M(II) showed higher thermal stabilities than the PUF and also ascribed that the PUF-Cu(II) showed better thermal stability than the other PUF-M(II). The kinetic parameters such as activation energy, pre-exponential factor etc., were evaluated for these polymer metal complexes using Coats-Redfern equation. In addition, the antimicrobial activity of the synthesized polymers was tested against several microorganisms using agar well diffusion methods. Among all of the PUF-M(II), the antimicrobial activity of the PUF-Cu(II) showed the highest zone of inhibition because of its higher stability constant and may be used in biomedical applications.
Activation of PPARδ counteracts angiotensin II-induced ROS generation by inhibiting rac1 translocation in vascular smooth muscle cells.

PubMed

Lee, Hanna; Ham, Sun Ah; Kim, Min Young; Kim, Jae-Hwan; Paek, Kyung Shin; Kang, Eun Sil; Kim, Hyo Jung; Hwang, Jung Seok; Yoo, Taesik; Park, Chankyu; Kim, Jin-Hoi; Lim, Dae-Seog; Han, Chang Woo; Seo, Han Geuk

2012-07-01

Angiotensin II (Ang II)-mediated modification of the redox milieu of vascular smooth muscle cells (VSMCs) has been implicated in several pathophysiological processes, including cell proliferation, migration and differentiation. In this study, we demonstrate that the peroxisome proliferator-activated receptor (PPAR) δ counteracts Ang II-induced production of reactive oxygen species (ROS) in VSMCs. Activation of PPARδ by GW501516, a specific ligand for PPARδ, significantly reduced Ang II-induced ROS generation in VSMCs. This effect was, however, reversed in the presence of small interfering (si)RNA against PPARδ. The marked increase in ROS levels induced by Ang II was also eliminated by the inhibition of phosphatidylinositol 3-kinase (PI3K) but not of protein kinase C, suggesting the involvement of the PI3K/Akt signalling pathway in this process. Accordingly, ablation of Akt with siRNA further enhanced the inhibitory effects of GW501516 in Ang II-induced superoxide production. Ligand-activated PPARδ also blocked Ang II-induced translocation of Rac1 to the cell membrane, inhibiting the activation of NADPH oxidases and consequently ROS generation. These results indicate that ligand-activated PPARδ plays an important role in the cellular response to oxidative stress by decreasing ROS generated by Ang II in vascular cells.
Aldosterone does not require angiotensin II to activate NCC through a WNK4-SPAK-dependent pathway.

PubMed

van der Lubbe, Nils; Lim, Christina H; Meima, Marcel E; van Veghel, Richard; Rosenbaek, Lena Lindtoft; Mutig, Kerim; Danser, Alexander H J; Fenton, Robert A; Zietse, Robert; Hoorn, Ewout J

2012-06-01

We and others have recently shown that angiotensin II can activate the sodium chloride cotransporter (NCC) through a WNK4-SPAK-dependent pathway. Because WNK4 was previously shown to be a negative regulator of NCC, it has been postulated that angiotensin II converts WNK4 to a positive regulator. Here, we ask whether aldosterone requires angiotensin II to activate NCC and if their effects are additive. To do so, we infused vehicle or aldosterone in adrenalectomized rats that also received the angiotensin receptor blocker losartan. In the presence of losartan, aldosterone was still capable of increasing total and phosphorylated NCC twofold to threefold. The kinases WNK4 and SPAK also increased with aldosterone and losartan. A dose-dependent relationship between aldosterone and NCC, SPAK, and WNK4 was identified, suggesting that these are aldosterone-sensitive proteins. As more functional evidence of increased NCC activity, we showed that rats receiving aldosterone and losartan had a significantly greater natriuretic response to hydrochlorothiazide than rats receiving losartan only. To study whether angiotensin II could have an additive effect, rats receiving aldosterone with losartan were compared with rats receiving aldosterone only. Rats receiving aldosterone only retained more sodium and had twofold to fourfold increase in phosphorylated NCC. Together, our results demonstrate that aldosterone does not require angiotensin II to activate NCC and that WNK4 appears to act as a positive regulator in this pathway. The additive effect of angiotensin II may favor electroneutral sodium reabsorption during hypovolemia and may contribute to hypertension in diseases with an activated renin-angiotensin-aldosterone system.
Long-term soluble Abeta1-40 activates CaM kinase II in organotypic hippocampal cultures.

PubMed

Tardito, Daniela; Gennarelli, Massimo; Musazzi, Laura; Gesuete, Raffaella; Chiarini, Stefania; Barbiero, Valentina Sara; Rydel, Russell E; Racagni, Giorgio; Popoli, Maurizio

2007-09-01

Recent findings suggested a role for soluble amyloid-beta (Abeta) peptides in Alzheimer's disease associated cognitive decline. We investigated the action of soluble, monomeric Abeta(1-40) on CaM kinase II, a kinase involved in neuroplasticity and cognition. We treated organotypic hippocampal cultures short-term (up to 4h) and long-term (5 days) with Abeta(1-40) (1nM-5microM). Abeta did not induce cell damage, apoptosis or synaptic loss. Short-term treatment down-regulated enzymatic activity of the kinase, by reducing its Thr(286) phosphorylation. In contrast, long-term treatment (1nM-microM) markedly and significantly up-regulated enzymatic activity, with peak stimulation at 10nM (three-fold). Up-regulation of activity was associated with increased expression of the alpha-isoform of CaM kinase II, increased phosphorylation at Thr(286) (activator residue) and decreased phosphorylation at Thr(305-306) (inhibitory residues). We investigated the effect of glutamate on CaM kinase II following exposure to 1 or 10nM Abeta(1-40). As previously reported, glutamate increased CaM kinase II activity. However, the glutamate effect was not altered by pretreatment of slices with Abeta. Short- and long-term Abeta treatment showed opposite effects on CaM kinase II, suggesting that long-term changes are an adaptation to the kinase early down-regulation. The marked effect of Abeta(1-40) on the kinase suggests that semi-physiological and slowly raising peptide concentrations may have a significant impact on synaptic plasticity in the absence of synaptic loss or neuronal cell death.
Nickel(II) and copper(II) complexes of N,N-dialkyl-N‧-3-chlorobenzoylthiourea: Synthesis, characterization, crystal structures, Hirshfeld surfaces and antimicrobial activity

NASA Astrophysics Data System (ADS)

Binzet, Gun; Gumus, Ilkay; Dogen, Aylin; Flörke, Ulrich; Kulcu, Nevzat; Arslan, Hakan

2018-06-01

We synthesized four new N,N-dialkyl-N‧-3-chlorobenzoylthiourea ligands (Alkyl: Dimethyl, diethyl, di-n-propyl and di-n-butyl) and their metal complexes with copper and nickel atoms. The structure of all synthesized compounds was fully characterized by physicochemical, spectroscopic and single crystal X-ray diffraction analysis techniques. The physical, spectral and analytical data of the newly synthesized metal complexes have shown the formation of 1:2 (metal:ligand) ratio. The benzoylthiourea ligands coordinate with metal atoms through oxygen and sulphur atoms. The metal atoms are in slightly distorted square-planar coordination geometry in Ni(II) or Cu(II) complex. Two oxygen and two sulphur atoms are mutually cis to each other in Ni(II) or Cu(II) complex. The intermolecular contacts in the compounds, which are HL1 and HL3, were examined by Hirshfeld surfaces and fingerprint plots using the data obtained from X-ray single crystal diffraction measurement. Besides these, their antimicrobial activities against Gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus, Streptococcus pyogenes and Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and anti-yeast activity (Candida glabrata, Candida parapsilosis and Candida albicans) were investigated. This exhibited some promising results towards testing organism. Among all the compounds, Ni(L1)2 complex showed high activity against Bacillus subtilis with MIC values at 7.81 μg/mL.
8 CFR 329.5 - Natives of the Philippines with active duty service during World War II.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 8 Aliens and Nationality 1 2011-01-01 2011-01-01 false Natives of the Philippines with active duty service during World War II. 329.5 Section 329.5 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY... Natives of the Philippines with active duty service during World War II. (a) A person desiring to...
Msn2p/Msn4p act as a key transcriptional activator of yeast cytoplasmic thiol peroxidase II.

PubMed

Hong, Seung-Keun; Cha, Mee-Kyung; Choi, Yong-Soo; Kim, Won-Cheol; Kim, Il-Han

2002-04-05

We observed that the transcription of Saccharomyces cerevisiae cytoplasmic thiol peroxidase type II (cTPx II) (YDR453C) is regulated in response to various stresses (e.g. oxidative stress, carbon starvation, and heat-shock). It has been suggested that both transcription-activating proteins, Yap1p and Skn7p, regulate the transcription of cTPx II upon exposure to oxidative stress. However, a dramatic loss of transcriptional response to various stresses in yeast mutant strains lacking both Msn2p and Msn4p suggests that the transcription factors act as a principal transcriptional activator. In addition to two Yap1p response elements (YREs), TTACTAA and TTAGTAA, the presence of two stress response elements (STREs) (CCCCT) in the upstream sequence of cTPx II also suggests that Msn2p/Msn4p could control stress-induced expression of cTPx II. Analysis of the transcriptional activity of site-directed mutagenesis of the putative STREs (STRE1 and STRE2) and YREs (TRE1 and YRE2) in terms of the activity of a lacZ reporter gene under control of the cTPx II promoter indicates that STRE2 acts as a principal binding element essential for transactivation of the cTPx II promoter. The transcriptional activity of the cTPx II promoter was exponentially increased after postdiauxic growth. The transcriptional activity of the cTPx II promoter is greatly increased by rapamycin. Deletion of Tor1, Tor2, Ras1, and Ras2 resulted in a considerable induction when compared with their parent strains, suggesting that the transcription of cTPx II is under negative control of the Ras/cAMP and target of rapamycin signaling pathways. Taken together, these results suggest that cTPx II is a target of Msn2p/Msn4p transcription factors under negative control of the Ras-protein kinase A and target of rapamycin signaling pathways. Furthermore, the accumulation of cTPx II upon exposure to oxidative stress and during the postdiauxic shift suggests an important antioxidant role in stationary phase yeast cells.
Tripeptidyl-peptidase II (TPP II) inhibitory activity of (S)-2,3-dihydro-2-(1H-imidazol-2-yl)-1H-indoles, a systematic SAR evaluation. Part 2.

PubMed

Breslin, Henry J; Miskowski, Tamara A; Kukla, Michael J; De Winter, Hans L; Somers, Maria V F; Roevens, Peter W M; Kavash, Robert W

2003-12-15

We have systematically explored the structure-activity relationship (SAR) for a series of compounds 2 as inhibitors of tripeptidyl-peptidase II (TPP II), a serine protease responsible for the degradation of cholecystokinin-8 (CCK-8). This SAR evaluation of the core structure 2 suggest a fairly restrictive pharmacophore for such related structures, but has yielded a limited set of compounds (2b, 2c, 2d, 2s, and 2t) with potent TPP II inhibitory activity (IC(50) 4-11 nM).
Effect of Melanotan-II on Brain Fos Immunoreactivity and Oxytocin Neuronal Activity and Secretion in Rats.

PubMed

Paiva, L; Sabatier, N; Leng, G; Ludwig, M

2017-02-01

Melanocortins stimulate the central oxytocin systems that are involved in regulating social behaviours. Alterations in central oxytocin have been linked to neurological disorders such as autism, and melanocortins have been proposed for therapeutic treatment. In the present study, we investigated how systemic administration of melanotan-II (MT-II), a melanocortin agonist, affects oxytocin neuronal activity and secretion in rats. The results obtained show that i.v., but not intranasal, administration of MT-II markedly induced Fos expression in magnocellular neurones of the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus, and this response was attenuated by prior i.c.v. administration of the melanocortin antagonist, SHU-9119. Electrophysiological recordings from identified magnocellular neurones of the SON showed that i.v. administration of MT-II increased the firing rate in oxytocin neurones but did not trigger somatodendritic oxytocin release within the SON as measured by microdialysis. Our data suggest that, after i.v., but not intranasal, administration of MT-II, the activity of magnocellular neurones of the SON is increased. Because previous studies showed that SON oxytocin neurones are inhibited in response to direct application of melanocortin agonists, the actions of i.v. MT-II are likely to be mediated at least partly indirectly, possibly by activation of inputs from the caudal brainstem, where MT-II also increased Fos expression. © 2016 British Society for Neuroendocrinology.
Palladium(II) and platinum(II) derivatives of benzothiazoline ligands: Synthesis, characterization, antimicrobial and antispermatogenic activity

NASA Astrophysics Data System (ADS)

Sharma, Krishna; Singh, R. V.; Fahmi, Nighat

2011-01-01

A series of Pd(II) and Pt(II) complexes with two N ∩S donor ligands, 5-chloro-3-(indolin-2-one)benzothiazoline and 6-nitro-3-(indolin-2-one)benzothiazoline, have been synthesized by the reaction of metal chlorides (PdCl 2 and PtCl 2) with ligands in 1:2 molar ratios. All the synthesized compounds were characterized by elemental analyses, melting point determinations and a combination of electronic, IR, 1H NMR and 13C NMR spectroscopic techniques for structure elucidation. In order to evaluate the effect of metal ions upon chelation, both the ligands and their complexes have been screened for their antimicrobial activity against the various pathogenic bacterial and fungal strains. The metal complexes have shown to be more antimicrobial against the microbial species as compared to free ligands. One of the ligands, 5-chloro-3-(indolin-2-one)benzothiazoline and its corresponding palladium and platinum complexes have been tested for their antifertility activity in male albino rats. The marked reduction in sperm motility and density resulted in infertility by 62-90%. Significant alterations were found in biochemical parameters of reproductive organs in treated animals as compared to control group. It is concluded that all these effects may finally impair the fertility of male rats.
Evidence for a reduced heparin cofactor II biological activity in diabetes.

PubMed

Ceriello, A; Quatraro, A; Dello Russo, P; Marchi, E; Milani, M R; Giugliano, D

1990-01-01

A reduction of heparin cofactor II (HCII) biological activity, despite its normal plasma concentration, is reported in insulin-dependent diabetic patients. A good linear correlation between HCII activity and concentration is present in normal controls but not in diabetics. In these subjects HCII activity correlates inversely with fasting blood glucose and glycated proteins but not with Hb A1. These data demonstrate the presence of a depressed HCII activity in the presence of its normal plasma concentration in insulin-dependent diabetics and suggest a role for short-term metabolic control in conditioning this phenomenon.
Kinetics, equilibrium, and thermodynamics investigation on the adsorption of lead(II) by coal-based activated carbon.

PubMed

Yi, Zhengji; Yao, Jun; Zhu, Mijia; Chen, Huilun; Wang, Fei; Liu, Xing

2016-01-01

The goal of this research is to investigate the feasibility of using activated coal-based activated carbon (CBAC) to adsorb Pb(II) from aqueous solutions through batch tests. Effects of contact time, pH, temperature and initial Pb(II) concentration on the Pb(II) adsorption were examined. The Pb(II) adsorption is strongly dependent on pH, but insensitive to temperature. The best pH for Pb(II) removal is in the range of 5.0-5.5 with more than 90 % of Pb(II) removed. The equilibrium time was found to be 60 min and the adsorption data followed the pseudo-second-order kinetics. Isotherm data followed Langmuir isotherm model with a maximum adsorption capacity of 162.33 mg/g. The adsorption was exothermic and spontaneous in nature. The Fourier transform infrared spectroscopy and scanning electron microscopy analysis suggested that CBAC possessed a porous structure and was rich in carboxyl and hydroxyl groups on its surface, which might play a major role in Pb(II) adsorption. These findings indicated that CBAC has great potential as an alternative adsorbent for Pb(II) removal.
Inhibition of calcium/calmodulin kinase II alpha subunit expression results in epileptiform activity in cultured hippocampal neurons.

PubMed

Churn, S B; Sombati, S; Jakoi, E R; Severt, L; DeLorenzo, R J; Sievert, L

2000-05-09

Several models that develop epileptiform discharges and epilepsy have been associated with a decrease in the activity of calmodulin-dependent kinase II. However, none of these studies has demonstrated a causal relationship between a decrease in calcium/calmodulin kinase II activity and the development of seizure activity. The present study was conducted to determine the effect of directly reducing calcium/calmodulin-dependent kinase activity on the development of epileptiform discharges in hippocampal neurons in culture. Complimentary oligonucleotides specific for the alpha subunit of the calcium/calmodulin kinase were used to decrease the expression of the enzyme. Reduction in kinase expression was confirmed by Western analysis, immunocytochemistry, and exogenous substrate phosphorylation. Increased neuronal excitability and frank epileptiform discharges were observed after a significant reduction in calmodulin kinase II expression. The epileptiform activity was a synchronous event and was not caused by random neuronal firing. Furthermore, the magnitude of decreased kinase expression correlated with the increased neuronal excitability. The data suggest that decreased calmodulin kinase II activity may play a role in epileptogenesis and the long-term plasticity changes associated with the development of pathological seizure activity and epilepsy.
Inhibition of calcium/calmodulin kinase II alpha subunit expression results in epileptiform activity in cultured hippocampal neurons

PubMed Central

Churn, Severn B.; Sombati, Sompong; Jakoi, Emma R.; Sievert, Lawrence; DeLorenzo, Robert J.

2000-01-01

Several models that develop epileptiform discharges and epilepsy have been associated with a decrease in the activity of calmodulin-dependent kinase II. However, none of these studies has demonstrated a causal relationship between a decrease in calcium/calmodulin kinase II activity and the development of seizure activity. The present study was conducted to determine the effect of directly reducing calcium/calmodulin-dependent kinase activity on the development of epileptiform discharges in hippocampal neurons in culture. Complimentary oligonucleotides specific for the α subunit of the calcium/calmodulin kinase were used to decrease the expression of the enzyme. Reduction in kinase expression was confirmed by Western analysis, immunocytochemistry, and exogenous substrate phosphorylation. Increased neuronal excitability and frank epileptiform discharges were observed after a significant reduction in calmodulin kinase II expression. The epileptiform activity was a synchronous event and was not caused by random neuronal firing. Furthermore, the magnitude of decreased kinase expression correlated with the increased neuronal excitability. The data suggest that decreased calmodulin kinase II activity may play a role in epileptogenesis and the long-term plasticity changes associated with the development of pathological seizure activity and epilepsy. PMID:10779547

Inhibiting prolyl isomerase activity by hybrid organic-inorganic molecules containing rhodium(II) fragments.

PubMed

Coughlin, Jane M; Kundu, Rituparna; Cooper, Julian C; Ball, Zachary T

2014-11-15

A small molecule containing a rhodium(II) tetracarboxylate fragment is shown to be a potent inhibitor of the prolyl isomerase FKBP12. The use of small molecules conjugates of rhodium(II) is presented as a general strategy for developing new protein inhibitors based on distinct structural and sequence features of the enzyme active site. Copyright © 2014 Elsevier Ltd. All rights reserved.
Structural, physicochemical characterization, theoretical studies of carboxamides and their Cu(II), Zn(II) complexes having antibacterial activities against E. coli

NASA Astrophysics Data System (ADS)

Aktan, Ebru; Gündüzalp, Ayla Balaban; Özmen, Ümmühan Özdemir

2017-01-01

The carboxamides; N,N‧-bis(thiophene-2-carboxamido)-1,3-diaminopropanol (L1) and N,N‧-bis(furan-2-carboxamido)-1,3-diaminopropanol (L2) were synthesized and characterized using 1H NMR, 13C NMR, LC-MS and FT-IR spectrum. The molecular geometries of these molecules were optimized by DFT/B3LYP method with 6-311G(d,p) basis set in Gaussian 09 software. The geometrical parameters, frontier molecular orbitals (FMOs) and molecular electrostatic potential (MEP) mapped surfaces were calculated by the same basis set. Dinuclear Cu(II) and Zn(II) complexes having general formula as [MLCl]2Cl2.nH2O (in which M = Cu(II),Zn(II); n = 0,2) were also synthesized and characterized using LC-MS and FT-IR spectrum, thermogravimetric analysis (TGA/DTA curves), magnetic moments and molar conductivities. Coordination was found to be through carbonyl oxygen and two chlorine atoms as bridging in distorted tetrahedral geometry. The optimized structures, geometrical parameters, frontier molecular orbitals (FMOs) and dipole moments of metal complexes were also obtained by DFT/B3LYP method with LanL2DZ basis set. Antibacterial activities of the compounds were screened against E. coli using microdilution method (MIC's in μg/mL). The activity results show that the corresponding compounds exhibit good to moderate antibacterial effects when compared with sulfamethoxazole and sulfisoxazole antibiotics as positive controls. Also, metal complexes have remarkable increase in their activities than parent ligands against E. coli which is mostly effected by [Cu(L2)Cl]2Cl2 complex as potential antibacterial agent.
Microfluidic Investigation Reveals Distinct Roles for Actin Cytoskeleton and Myosin II Activity in Capillary Leukocyte Trafficking

PubMed Central

Gabriele, Sylvain; Benoliel, Anne-Marie; Bongrand, Pierre; Théodoly, Olivier

2009-01-01

Circulating leukocyte sequestration in pulmonary capillaries is arguably the initiating event of lung injury in acute respiratory distress syndrome. We present a microfluidic investigation of the roles of actin organization and myosin II activity during the different stages of leukocyte trafficking through narrow capillaries (entry, transit and shape relaxation) using specific drugs (latrunculin A, jasplakinolide, and blebbistatin). The deformation rate during entry reveals that cell stiffness depends strongly on F-actin organization and hardly on myosin II activity, supporting a microfilament role in leukocyte sequestration. In the transit stage, cell friction is influenced by stiffness, demonstrating that the actin network is not completely broken after a forced entry into a capillary. Conversely, membrane unfolding was independent of leukocyte stiffness. The surface area of sequestered leukocytes increased by up to 160% in the absence of myosin II activity, showing the major role of molecular motors in microvilli wrinkling and zipping. Finally, cell shape relaxation was largely independent of both actin organization and myosin II activity, whereas a deformed state was required for normal trafficking through capillary segments. PMID:19450501
Angiotensin II promotes the proliferation of activated pancreatic stellate cells by Smad7 induction through a protein kinase C pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hama, Kouji; Ohnishi, Hirohide; Aoki, Hiroyoshi

2006-02-17

Activated pancreatic stellate cells (PSCs) play major roles in promoting pancreatic fibrosis. We previously reported that angiotensin II (Ang II) enhances activated PSC proliferation through EGF receptor transactivation. In the present study, we elucidated a novel intracellular mechanism by which Ang II stimulates cellular proliferation. TGF-{beta}{sub 1} inhibits activated PSC proliferation via a Smad3 and Smad4-dependent pathway in an autocrine manner. We demonstrated that Ang II inhibited TGF-{beta}{sub 1}-induced nuclear accumulation of Smad3 and Smad4. Furthermore, Ang II rapidly induced inhibitory Smad7 mRNA expression. Adenovirus-mediated Smad7 overexpression inhibited TGF-{beta}{sub 1}-induced nuclear accumulation of Smad3 and Smad4, and potentiated activated PSCmore » proliferation. PKC inhibitor Go6983 blocked the induction of Smad7 mRNA expression by Ang II. In addition, 12-O-tetradecanoyl-phorbol 13-acetate, a PKC activator, increased Smad7 mRNA expression. These results suggest that Ang II enhances activated PSC proliferation by blocking autocrine TGF-{beta}{sub 1}-mediated growth inhibition by inducing Smad7 expression via a PKC-dependent pathway.« less
Synthesis, characterization and anti-microbial activity of phenylurea-formaldehyde resin (PUF) and its polymer metal complexes (PUF-Mn(II).

PubMed

Ahamad, Tansir; Alshehri, Saad M

2012-10-01

Phenylurea-formaldehyde polymer (PUF) was synthesized via polycondensation of phenylurea and formaldehyde in basic medium, its polymer-metal complexes [PUF-M(II)] were prepared with Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) ions. PUF and PUF-M(II) were characterized with magnetic moment measurements, elemental and spectral (UV-visible, FTIR, 1H-NMR, 13C-NMR and ESR) analysis. The thermal behaviors of all the synthesized polymers were carried out using thermogravimetric analysis (TGA) and differential thermal analysis (DTA). The thermal data revealed that all of the PUF-M(II) showed higher thermal stabilities than the PUF and also ascribed that the PUF-Cu(II) showed better thermal stability than the other PUF-M(II). The kinetic parameters such as activation energy, pre-exponential factor etc., were evaluated for these polymer metal complexes using Coats-Redfern equation. In addition, the antimicrobial activity of the synthesized polymers was tested against several microorganisms using agar well diffusion methods. Among all of the PUF-M(II), the antimicrobial activity of the PUF-Cu(II) showed the highest zone of inhibition because of its higher stability constant and may be used in biomedical applications. Copyright © 2012 Elsevier B.V. All rights reserved.
Oxoaporphine Metal Complexes (CoII, NiII, ZnII) with High Antitumor Activity by Inducing Mitochondria-Mediated Apoptosis and S-phase Arrest in HepG2

PubMed Central

Qin, Jiao-Lan; Shen, Wen-Ying; Chen, Zhen-Feng; Zhao, Li-Fang; Qin, Qi-Pin; Yu, Yan-Cheng; Liang, Hong

2017-01-01

Three new oxoaporphine Co(II), Ni(II) and Zn(II) complexes 1–3 have been synthesized and fully characterized. 1–3 have similar mononuclear structures with the metal and ligand ratio of 1:2. 1–3 exhibited higher cytotoxicity than the OD ligand and cisplatin against HepG2, T-24, BEL-7404, MGC80–3 and SK-OV-3/DDP cells, with IC50 value of 0.23−4.31 μM. Interestingly, 0.5 μM 1–3 significantly caused HepG2 arrest at S-phase, which was associated with the up-regulation of p53, p21, p27, Chk1 and Chk2 proteins, and decrease in cyclin A, CDK2, Cdc25A, PCNA proteins. In addition, 1–3 induced HepG2 apoptosis via a caspase-dependent mitochondrion pathway as evidenced by p53 activation, ROS production, Bax up-regulation and Bcl-2 down-regulation, mitochondrial dysfunction, cytochrome c release, caspase activation and PARP cleavage. Furthermore, 3 inhibited tumor growth in HepG2 xenograft model, and displayed more safety profile in vivo than cisplatin. PMID:28436418
Surgery in World War II. Activities of Surgical Consultants. Volume 2

DTIC Science & Technology

1964-01-01

708 ACTIVITIES OF SURGICAL CONSULTANTS 12o0* 130 40 L Ingoyen * MOUNTING AREA Gulf PHILIPPINE 0 0oo IANILA MILES 1, % P A C /F /C X• Leyte 15o- 1-10...comprised one of the two attack forces of the Seventh Fleet in the asault on the Philippines . 856 ACTIVITIES OF SURIGICAL CONSULTANTS any real 1... ACTIVITIES OF SURGICAL CONSULTANTS Volume II Prepared and published under the direction of Lieutenant General LEONARD D. HIEATON The Surgeon General, United
N-((5-chloropyridin-2-yl)carbamothioyl)furan-2-carboxamide and its Co(II), Ni(II) and Cu(II) complexes: Synthesis, characterization, DFT computations, thermal decomposition, antioxidant and antitumor activity

NASA Astrophysics Data System (ADS)

Yeşilkaynak, Tuncay; Özpınar, Celal; Emen, Fatih Mehmet; Ateş, Burhan; Kaya, Kerem

2017-02-01

N-((5-chloropyridin-2-yl)carbamothioyl)furan-2-carboxamide (HL: C11H8ClN3O2S) and its Co(II), Ni(II) and Cu(II) complexes have been synthesized and characterized by elemental analysis, FT-IR,1H NMR and HR-MS methods. The HL was characterized by single crystal X-ray diffraction technique. It crystallizes in the monoclinic system. The HL has the space group P 1 21/c 1, Z = 4, and its unit cell parameters are a = 4.5437(5) Å, b = 22.4550(3) Å, c = 11.8947(14) Å. The ligand coordinates the metal ions as bidentate and thus essentially yields neutral complexes of the [ML2] type. ML2 complex structures were optimized using B97D/TZVP level. Molecular orbitals of both HL ligand were calculated at the same level. Thermal decomposition of the complexes has been investigated by thermogravimetry. The complexes were screened for their anticancer and antioxidant activities. Antioxidant activity of the complexes was determined by using the DPPH and ABTS assays. The anticancer activity of the complexes was studied by using MTT assay in MCF-7 breast cancer cells.
Synthesis and antitumor activity of seleno- and thio-purines complexed with cis-diamminoplatinum (II).

PubMed

Maeda, M; Abiko, N; Sasaki, T

1982-02-01

cis-Diamminoplatinum (II) complexes with selenoguanine, thioguanine, 6-thioxanthine, or 6-mercaptopurine were synthesized by the reaction of stoichiometric amounts of selenopurine or thiopurine with aquated cis-dichlorodimmineplatinum (II) in slightly acidic medium, and their antitumor activity was studied against L1210 cells in mice. These compounds exhibited a medium antitumor activity with very low toxicity. The antitumor activity was dependent on the nature of the purine ligand. These complexes were very stable in various aqueous solvents at 37 degrees C for 10 d but not in the presence of mouse serum. The mechanism of the action effected by the complex is not clear. However, the slow release of an antitumor active purine from the complex, SeG-Pt (NH3)2, was observed.
Structural characterization of 1,8-naphthalimides and in vitro microbiological activity of their Cu(II) and Zn(II) complexes

NASA Astrophysics Data System (ADS)

Grabchev, Ivo; Yordanova, Stanislava; Bosch, Paula; Vasileva-Tonkova, Evgenia; Kukeva, Rositsa; Stoyanov, Stanimir; Stoyanova, Radostina

2017-02-01

Two new 1,8-naphthalimide derivatives (NI1 and NI2) have been synthesized and characterized. The photophysical properties of the new compounds have been investigated in organic solvents of different polarity. It has been shown that both compounds are solvent depended. Cu(II) and Zn(II) complexes of NI2 were obtained and characterized by IR-NMR, fluorescence and EPR spectroscopy. The influence of different metal cations on the fluorescence intensity has been investigated in acetonitrile solution. Antimicrobial composite PLA-metal complexes materials have been obtained for the first time. Microbiological activity of both metal complexes has been investigated in vitro against different Gram-positive and Gram-negative bacteria and two yeasts. The various antimicrobial activities and the minimum inhibitory concentrations (MICs) of both complexes have been determined. The microbiological activity of composite materials PLA-metal complexes in thin polymeric film has also been investigated. The results suggest that the new metal complexes could find application in designing new antimicrobial preparations to control the spread of infections.
Efficient adsorption of Hg (II) ions in water by activated carbon modified with melamine

NASA Astrophysics Data System (ADS)

Qin, Hangdao; Meng, Jingling; Chen, Jing

2018-04-01

Removal of Hg (II) ions from industrial wastewater is important for the water treatment, and adsorption is an efficient treatment process. Activated carbon (AC) was modified with melamine, which introduced nitrogen-containing functional groups onto AC surface. Original AC and melamine modified activated carbon (ACM) were characterized by elemental analysis, N2 adsorption-desorption, determination of the pH of the point of zero charge (pHpzc) and X-ray photoelectron spectroscopy (XPS) and their performance in the adsorption of Hg(II) ions was investigated. Langmuir model fitted the experimental data of equilibrium isotherms well. ACM showed the higher Hg (II) ions adsorption capacity, increasing more than more than 1.8 times compared to the original one. Moreover, ACM showed a wider pH range for the maximum adsorption than the parent AC.
Activation and reactivation of the RNA polymerase II trigger loop for intrinsic RNA cleavage and catalysis

PubMed Central

Čabart, Pavel; Jin, Huiyan; Li, Liangtao; Kaplan, Craig D

2014-01-01

In addition to RNA synthesis, multisubunit RNA polymerases (msRNAPs) support enzymatic reactions such as intrinsic transcript cleavage. msRNAP active sites from different species appear to exhibit differential intrinsic transcript cleavage efficiency and have likely evolved to allow fine-tuning of the transcription process. Here we show that a single amino-acid substitution in the trigger loop (TL) of Saccharomyces RNAP II, Rpb1 H1085Y, engenders a gain of intrinsic cleavage activity where the substituted tyrosine appears to participate in acid-base chemistry at alkaline pH for both intrinsic cleavage and nucleotidyl transfer. We extensively characterize this TL substitution for each of these reactions by examining the responses RNAP II enzymes to catalytic metals, altered pH, and factor inputs. We demonstrate that TFIIF stimulation of the first phosphodiester bond formation by RNAP II requires wild type TL function and that H1085Y substitution within the TL compromises or alters RNAP II responsiveness to both TFIIB and TFIIF. Finally, Mn2+ stimulation of H1085Y RNAP II reveals possible allosteric effects of TFIIB on the active center and cooperation between TFIIB and TFIIF. PMID:25764335
Depression of neuronal excitability and epileptic activities by group II metabotropic glutamate receptors in the medial entorhinal cortex.

PubMed

Zhang, Haopeng; Cilz, Nicholas I; Yang, Chuanxiu; Hu, Binqi; Dong, Hailong; Lei, Saobo

2015-11-01

Whereas the ionotropic glutamate receptors are the major mediator in glutamatergic transmission, the metabotropic glutamate receptors (mGluRs) usually play a modulatory role. Whereas the entorhinal cortex (EC) is an essential structure involved in the generation and propagation of epilepsy, the roles and mechanisms of mGluRs in epilepsy in the EC have not been determined. Here, we studied the effects of activation of group II metabotropic glutamate receptors (mGluRs II) on epileptiform activity induced by picrotoxin or deprivation of extracellular Mg2+ and neuronal excitability in the medial EC. We found that activation of mGluRs II by application of the selective agonist, LY354740, exerted robust inhibition on epileptiform activity. LY354740 hyperpolarized entorhinal neurons via activation of a K+ conductance and inhibition of a Na+ -permeable channel. LY354740-induced hyperpolarization was G protein-dependent, but independent of adenylyl cyclase and protein kinase A. However, the function of Gβγ was involved in mGluRs II-mediated depression of both neuronal excitability and epileptiform activity. Our results provide a novel cellular mechanism to explain the antiepileptic effects of mGluRs II in the treatment of epilepsy. © 2015 Wiley Periodicals, Inc.
CHBPR: ANGIOTENSIN II, INDEPENDENT OF PLASMA RENIN ACTIVITY, CONTRIBUTES TO THE HYPERTENSION OF AUTONOMIC FAILURE

PubMed Central

Arnold, Amy C.; Okamoto, Luis E.; Gamboa, Alfredo; Shibao, Cyndya; Raj, Satish R.; Robertson, David; Biaggioni, Italo

2013-01-01

At least half of primary autonomic failure patients exhibit supine hypertension, despite profound impairments in sympathetic activity. While the mechanisms underlying this hypertension are unknown, plasma renin activity is often undetectable suggesting renin-angiotensin pathways are not involved. However, because aldosterone levels are preserved, we tested the hypothesis that angiotensin II is intact and contributes to the hypertension of autonomic failure. Indeed, circulating angiotensin II was paradoxically increased in hypertensive autonomic failure patients (52±5 pg/ml, n=11) compared to matched healthy controls (27±4 pg/ml, n=10; p=0.002), despite similarly low renin activity (0.19±0.06 versus 0.34±0.13 ng/ml/hr, respectively; p=0.449). To determine the contribution of angiotensin II to supine hypertension in these patients, we administered the AT1 receptor blocker losartan (50 mg) at bedtime in a randomized, double-blind, placebo-controlled study (n=11). Losartan maximally reduced systolic blood pressure by 32±11 mmHg at 6 hours after administration (p<0.05), decreased nocturnal urinary sodium excretion (p=0.0461), and did not worsen morning orthostatic tolerance. In contrast, there was no effect of the captopril on supine blood pressure in a subset of these patients. These findings suggest that angiotensin II formation in autonomic failure is independent of plasma renin activity, and perhaps angiotensin converting enzyme. Furthermore, these studies suggest that elevations in angiotensin II contribute to the hypertension of autonomic failure, and provide rationale for the use of AT1 receptor blockers for treatment of these patients. PMID:23266540
Structure-activity studies of dicationically substituted bis-benzimidazoles against Giardia lamblia: correlation of antigiardial activity with DNA binding affinity and giardial topoisomerase II inhibition.

PubMed Central

Bell, C A; Dykstra, C C; Naiman, N A; Cory, M; Fairley, T A; Tidwell, R R

1993-01-01

Nine dicationically substituted bis-benzimidazoles were examined for their in vitro activities against Giardia lamblia WB (ATCC 30957). The potential mechanisms of action of these compounds were evaluated by investigating the relationship among in vitro antigiardial activity and the affinity of the molecules for DNA and their ability to inhibit the activity of giardial topoisomerase II. Each compound demonstrated antigiardial activity, as measured by assessing the incorporation of [methyl-3H]thymidine by giardial trophozoites exposed to the test agents. Three compounds exhibited excellent in vitro antigiardial activities, with 50% inhibitory concentrations which compared very favorably with those of two currently used drugs, quinacrine HCl and metronidazole. Putative mechanisms of action for these compounds were suggested by the strong correlation observed among in vitro antigiardial activity and the affinity of the molecules for natural and synthetic DNA and their ability to inhibit the relaxation activity of giardial topoisomerase II. A strong correlation between the DNA binding affinity of these compounds and their inhibition of giardial topoisomerase II activity was also observed. Images PMID:8109934
Adipokine CTRP6 improves PPARγ activation to alleviate angiotensin II-induced hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chi, Liyi; Departments of Cardiology, The 451st Hospital of People's Liberation Army; Hu, Xiaojing

Angiotensin II (AngII) is the most important component of angiotensin, which has been regarded as a major contributor to the incidence of hypertension and vascular endothelial dysfunction. The adipocytokine C1q/TNF-related protein 6 (CTRP6) was recently reported to have multiple protective effects on cardiac and cardiovascular function. However, the exact role of CTRP6 in the progression of AngII induced hypertension and vascular endothelial function remains unclear. Here, we showed that serum CTRP6 content was significantly downregulated in SHRs, accompanied by a marked increase in arterial systolic pressure and serum AngII, CRP and ET-1 content. Then, pcDNA3.1-mediated CTRP6 delivery or CTRP6 siRNAmore » was injected into SHRs. CTRP6 overexpression caused a significant decrease in AngII expression and AngII-mediated hypertension and vascular endothelial inflammation. In contrast, CTRP6 knockdown had the opposite effect to CTRP6 overexpression. Moreover, we found that CTRP6 positively regulated the activation of the ERK1/2 signaling pathway and the expression of peroxisome proliferator-activated receptor γ (PPARγ), a recently proven negative regulator of AngII, in the brain and vascular endothelium of SHRs. Finally, CTRP6 was overexpressed in endothelial cells, and caused a significant increase in PPARγ activation and suppression in AngII-mediated vascular endothelial dysfunction and apoptosis. The effect of that could be rescued by the ERK inhibitor PD98059. In contrast, silencing CTRP6 suppressed PPARγ activation and exacerbated AngII-mediated vascular endothelial dysfunction and apoptosis. In conclusion, CTRP6 improves PPARγ activation and alleviates AngII-induced hypertension and vascular endothelial dysfunction. - Highlights: • Serum CTRP6 was significantly decreased in spontaneously hypertensive rats (SHRs). • CTRP6 positively regulated the activation of the ERK1/2 signaling pathway. • CTRP6 negatively regulates PPARγ mediated Angiotensin II
New bioactive silver(I) complexes: Synthesis, characterization, anticancer, antibacterial and anticarbonic anhydrase II activities

NASA Astrophysics Data System (ADS)

Ozdemir, Ummuhan O.; Ozbek, Neslihan; Genc, Zuhal Karagoz; İlbiz, Firdevs; Gündüzalp, Ayla Balaban

2017-06-01

Silver(I) complexes of alkyl sulfonic acide hydrazides were newly synthesized as homologous series. Methanesulfonic acide hydrazide (L1), ethanesulfonic acide hydrazide (L2), propanesulfonic acide hydrazide (L3) and butanesulfonic acide hydrazide (L4) were used for complexation with Ag(I) ions. The silver complexes obtained in the mol ratio of 1:2 have the structural formula as Ag(L1)2NO3 (I), Ag(L2)2NO3 (II), Ag(L3)2NO3(III), (Ag(L4)2NO3 (IV). The Ag(I) complexes exhibit distorted linear two-fold coordination in [AgL2]+ cations with uncoordinated nitrates. Ligands are chelated with silver(I) ions through unsubstituted primary nitrogen in hydrazide group. Ag(I) complexes were characterized by using elemental analysis, spectroscopic methods (FT-IR, LC-MS), magnetic susceptibility and conductivity measurements. Silver(I) complexes were optimized using PBEPBE/LanL2DZ/DEF2SV basic set performed by DFT method with the Gaussian 09 program package. The geometrical parameters, frontier molecular orbitals (HOMOs and LUMOs) and molecular electrostatic potential (MEP) mapped surfaces of the optimized geometries were also determined by this quantum set. The anticancer activities of silver(I) complexes on MCF-7 human breast cancer cell line were investigated by comparing IC50 values. The antibacterial activities of complexes were studied against Gram positive bacteria; S. aureus ATCC 6538, B. subtilis ATCC 6633, B. cereus NRRL-B-3711, E. faecalis ATCC 29212 and Gram negative bacteria; E. coli ATCC 11230, P. aeruginosa ATCC 15442, K. pneumonia ATCC 70063 by using disc diffusion method. The inhibition activities of Ag(I) complexes on carbonic anhydrase II enzyme (hCA II) were also investigated by comparing IC50 and Ki values. The biological activity screening shows that Ag(I) complex of butanesulfonicacidehydrazide (IV) has the highest activity against tested breast cancer cell lines MCF-7, Gram positive/Gram negative bacteria and carbonic anhydrase II (hCA II) isoenzyme.
Angiotensin II stimulates calcineurin activity in proximal tubule epithelia through AT-1 receptor-mediated tyrosine phosphorylation of the PLC-gamma1 isoform.

PubMed

Lea, Janice P; Jin, Shao G; Roberts, Brian R; Shuler, Michael S; Marrero, Mario B; Tumlin, James A

2002-07-01

Angiotensin II (AngII) contributes to the maintenance of extracellular fluid volume by regulating sodium transport in the nephron. In nonepithelial cells, activation of phospholipase C (PLC) by AT-1 receptors stimulates the generation of 1,4,5-trisphosphate (IP(3)) and the release of intracellular calcium. Calcineurin, a serine-threonine phosphatase, is activated by calcium and calmodulin, and both PLC and calcineurin have been linked to sodium transport in the proximal tubule. An examination of whether AngII activates calcineurin in a model of proximal tubule epithelia (LLC-PK1 cells) was performed; AngII increased calcineurin activity within 30 s. An examination of whether AngII activates PLC in proximal tubule epithelia was also performed after first showing that all three families of PLC isoforms are present in LLC-PK1 cells. Application of AngII increased IP(3) generation by 60% within 15 s, which coincided with AngII-induced tyrosine phosphorylation of the PLC-gamma1 isoform also observed at 15 s. AngII-induced tyrosine phosphorylation was blocked by the AT-1 receptor antagonist, Losartan. Subsequently, an inhibitor of tyrosine phosphorylation blocked the AngII-induced activation of calcineurin, as did coincubation with an inhibitor of PLC activity and with an antagonist of the AT-1 receptor. It is therefore concluded that AngII stimulates calcineurin phosphatase activity in proximal tubule epithelial cells through a mechanism involving AT-1 receptor-mediated tyrosine phosphorylation of the PLC isoform.
20 CFR 404.1311 - Ninety-day active service requirement for World War II veterans.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Ninety-day active service requirement for World War II veterans. 404.1311 Section 404.1311 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Wage Credits for Veterans and Members of the Uniformed Services World War II Veterans §...
Bilirubin induces a calcium-dependent inhibition of multifunctional Ca2+/calmodulin-dependent kinase II activity in vitro.

PubMed

Churn, S B; DeLorenzo, R J; Shapiro, S M

1995-12-01

Excessive bilirubin levels in newborn infants result in long-term neurologic deficits that remain after bilirubin levels return to normal. Much of the observed neurologic deficits can be attributed to bilirubin-induced, delayed neuronal cell death. Inhibition of calcium/calmodulin-dependent kinase II (CaM kinase II) activity that precedes cell death is observed in conditions such as seizure activity, stroke, and glutamate excitotoxicity. Because neonatal bilirubin exposure results in neuronal loss in developing brain systems, we tested whether bilirubin exposure would induce an immediate inhibition of CaM activity, in vitro. P-81 filtration assay of basal and calcium-stimulated kinase activity was performed under standard kinase assay conditions. Bilirubin and/or albumin was added to the reaction vessels to determine the effect of these agents on kinase activity. Bilirubin exposure resulted in a concentration-dependent inhibition of CaM kinase II activity (IC50 = 16.78 microM). At concentrations above 50 microM, bilirubin exposure resulted in a 71 +/- 8% (mean +/- SD) inhibition of kinase activity (p < 0.001, t test, n = 10). Bilirubin exposure did not result in kinase inhibition if excessive bilirubin was removed by albumin binding before stimulation of kinase activity (106.9 +/- 9.6% control activity, n = 5). However, removal of bilirubin by binding with albumin after calcium addition did not restore kinase activity. (36.1 +/- 3.8% control activity, n = 5). Thus, once inhibition was observed, the activity could not be restored by addition of albumin. The data suggest that bilirubin exposure resulted in a calcium-dependent inhibition of CaM kinase II activity that, once induced, was not reversible by removing bilirubin by the addition of albumin. Because inhibition of CaM kinase II activity has been correlated with delayed neuronal cell death in many neuropathologic conditions, bilirubin-induced inhibition of this enzyme may be a cellular mechanism by which

TAF(II)250: a transcription toolbox.

PubMed

Wassarman, D A; Sauer, F

2001-08-01

Activation of RNA-polymerase-II-dependent transcription involves conversion of signals provided by gene-specific activator proteins into the synthesis of messenger RNA. This conversion requires dynamic structural changes in chromatin and assembly of general transcription factors (GTFs) and RNA polymerase II at core promoter sequence elements surrounding the transcription start site of genes. One hallmark of transcriptional activation is the interaction of DNA-bound activators with coactivators such as the TATA-box binding protein (TBP)-associated factors (TAF(II)s) within the GTF TFIID. TAF(II)250 possesses a variety of activities that are likely to contribute to the initial steps of RNA polymerase II transcription. TAF(II)250 is a scaffold for assembly of other TAF(II)s and TBP into TFIID, TAF(II)250 binds activators to recruit TFIID to particular promoters, TAF(II)250 regulates binding of TBP to DNA, TAF(II)250 binds core promoter initiator elements, TAF(II)250 binds acetylated lysine residues in core histones, and TAF(II)250 possesses protein kinase, ubiquitin-activating/conjugating and acetylase activities that modify histones and GTFs. We speculate that these activities achieve two goals--(1) they aid in positioning and stabilizing TFIID at particular promoters, and (2) they alter chromatin structure at the promoter to allow assembly of GTFs--and we propose a model for how TAF(II)250 converts activation signals into active transcription.
Nitric oxide inhibits ATPase activity and induces resistance to topoisomerase II-poisons in human MCF-7 breast tumor cells.

PubMed

Sinha, Birandra K; Kumar, Ashutosh; Mason, Ronald P

2017-07-01

Topoisomerase poisons are important drugs for the management of human malignancies. Nitric oxide ( • NO), a physiological signaling molecule, induces nitrosylation (or nitrosation) of many cellular proteins containing cysteine thiol groups, altering their cellular functions. Topoisomerases contain several thiol groups which are important for their activity and are also targets for nitrosation by nitric oxide. Here, we have evaluated the roles of • NO/ • NO-derived species in the stability and activity of topo II (α and β) both in vitro and in human MCF-7 breast tumor cells. Furthermore, we have examined the effects of • NO on the ATPase activity of topo II. Treatment of purified topo IIα and β with propylamine propylamine nonoate (PPNO), an NO donor, resulted in inhibition of the catalytic activity of topo II. Furthermore, PPNO significantly inhibited topo II-dependent ATP hydrolysis. • NO-induced inhibition of these topo II (α and β) functions resulted in a decrease in cleavable complex formation in MCF-7 cells in the presence of m-AMSA and XK469 and induced significant resistance to both drugs in MCF-7 cells. PPNO treatment resulted in the nitrosation of the topo II protein in MCF-7 cancer cells and inhibited both catalytic-, and ATPase activities of topo II. Furthermore, PPNO significantly affected the DNA damage and cytotoxicity of m-AMSA and XK469 in MCF-7 tumor cells. As tumors express nitric oxide synthase and generate • NO, inhibition of topo II functions by • NO/ • NO-derived species could render tumors resistant to certain topo II-poisons in the clinic.
The behaviour of the excess CA II H and K and Hɛ emissions in chromospherically active binaries.

NASA Astrophysics Data System (ADS)

Montes, D.; Fernandez-Figueroa, M. J.; Cornide, M.; de Castro, E.

1996-08-01

In this work we analyze the behaviour of the excess Ca II H and K and Hɛ emissions in a sample of 73 chromospherically active binary systems (RS CVn and BY Dra classes), of different activity levels and luminosity classes. This sample includes the 53 stars analyzed by Fernandez-Figueroa et al. (1994) and the observations of 28 systems described by Montes et al. (1995c). By using the spectral subtraction technique (subtraction of a synthesized stellar spectrum constructed from reference stars of spectral type and luminosity class similar to those of the binary star components) we obtain the active-chromosphere contribution to the Ca II H and K lines in these 73 systems. We have determined the excess Ca II H and K emission equivalent widths and converted them into surface fluxes. The emissions arising from each component were obtained when it was possible to deblend both contributions. We have found that the components of active binaries are generally stronger emitters than single active stars for a given effective temperature and rotation rate. A slight decline of the excess Ca II H and K emissions towards longer rotation periods, P_rot_, and larger Rossby numbers, R_0_, is found. When we use R_0_ instead of P_rot_ the scatter is reduced and a saturation at R_0_=~0.3 is observed. A good correlation between the excess Ca II K and Hɛ chromospheric emission fluxes has been found. The correlations obtained between the excess Ca II K emission and other activity indicators, (C IV in the transition region, and X-rays in the corona) indicate that the exponents of the power-law relations increase with the formation temperature of the spectral features.
Angiotensin II initiates tyrosine kinase Pyk2-dependent signalings leading to activation of Rac1-mediated c-Jun NH2-terminal kinase.

PubMed

Murasawa, S; Matsubara, H; Mori, Y; Masaki, H; Tsutsumi, Y; Shibasaki, Y; Kitabayashi, I; Tanaka, Y; Fujiyama, S; Koyama, Y; Fujiyama, A; Iba, S; Iwasaka, T

2000-09-01

Ca(2+)-sensitive tyrosine kinase Pyk2 was shown to be involved in angiotensin (Ang) II-mediated activation of extracellular signal-regulated kinase (ERK) via transactivation of epidermal growth factor receptor (EGF-R). In this study, we tested the involvement of Pyk2 and EGF-R in Ang II-induced activation of JNK and c-Jun in cardiac fibroblasts. Ang II markedly stimulated JNK activities, which were abolished by genistein and intracellular Ca(2+) chelators but partially by protein kinase C depletion. Inhibition of EGF-R did not affect Pyk2 and JNK activation by Ang II. Stable transfection with a dominant negative (DN) mutant for Pyk2 (PKM) completely blocked JNK activation by Ang II. DN mutants of Rac1 (DN-Rac1) and MEK kinase (DN-MEKK1) also abolished it, whereas those of Cdc42, RhoA, and Ha-Ras had no effect. Induction of c-Jun gene transcription by Ang II was abolished in PKM, DN-Rac1, and DN-MEKK1, in which Ang II-induced binding of ATF2/c-Jun heterodimer to the activator protein-1 sequence at -190 played a key role. These results suggest that 1) in cardiac fibroblasts activation of JNK and c-Jun by Ang II is initiated by Pyk2-dependent signalings but not by downstream signals of EGF-R or Ras, 2) Rac1 but not Cdc42 is required for JNK activation by Ang II upstream of MEKK1, and 3) ATF-2/c-Jun binding to the activator protein-1 sequence at -190 plays a key role for induction of c-Jun gene by Ang II.
Co(II) and Cd(II) Complexes Derived from Heterocyclic Schiff-Bases: Synthesis, Structural Characterisation, and Biological Activity

PubMed Central

Ahmed, Riyadh M.; Yousif, Enaam I.; Al-Jeboori, Mohamad J.

2013-01-01

New monomeric cobalt and cadmium complexes with Schiff-bases, namely, N′-[(E)-(3-hydroxy-4-methoxyphenyl)methylidene]furan-2-carbohydrazide (L1) and N′-[(E)-(3-hydroxy-4-methoxyphenyl)methylidene]thiophene-2-carbohydrazide (L2) are reported. Schiff-base ligands L1 and L2 were derived from condensation of 3-hydroxy-4-methoxybenzaldehyde (iso-vanillin) with furan-2-carboxylic acid hydrazide and thiophene-2-carboxylic acid hydrazide, respectively. Complexes of the general formula [M(L)2]Cl2 (where M = Co(II) or Cd(II), L = L1 or L2) have been obtained from the reaction of the corresponding metal chloride with the ligands. The ligands and their metal complexes were characterised by spectroscopic methods (FTIR, UV-Vis, 1H, and 13C NMR spectra), elemental analysis, metal content, magnetic measurement, and conductance. These studies revealed the formation of four-coordinate complexes in which the geometry about metal ion is tetrahedral. Biological activity of the ligands and their metal complexes against gram positive bacterial strain Bacillus (G+) and gram negative bacteria Pseudomonas (G−) revealed that the metal complexes become less resistive to the microbial activities as compared to the free ligands. PMID:24027449
Strong variable linear polarization in the cool active star II Peg

NASA Astrophysics Data System (ADS)

Rosén, Lisa; Kochukhov, Oleg; Wade, Gregg A.

2014-08-01

Magnetic fields of cool active stars are currently studied polarimetrically using only circular polarization observations. This provides limited information about the magnetic field geometry since circular polarization is only sensitive to the line-of-sight component of the magnetic field. Reconstructions of the magnetic field topology will therefore not be completely trustworthy when only circular polarization is used. On the other hand, linear polarization is sensitive to the transverse component of the magnetic field. By including linear polarization in the reconstruction the quality of the reconstructed magnetic map is dramatically improved. For that reason, we wanted to identify cool stars for which linear polarization could be detected at a level sufficient for magnetic imaging. Four active RS CVn binaries, II Peg, HR 1099, IM Peg, and σ Gem were observed with the ESPaDOnS spectropolarimeter at the Canada-France-Hawaii Telescope. Mean polarization profiles in all four Stokes parameters were derived using the multi-line technique of least-squares deconvolution (LSD). Not only was linear polarization successfully detected in all four stars in at least one observation, but also, II Peg showed an extraordinarily strong linear polarization signature throughout all observations. This qualifies II Peg as the first promising target for magnetic Doppler imaging in all four Stokes parameters and, at the same time, suggests that other such targets can possibly be identified.
[Adsorption kinetics and mechanism of lead (II) on polyamine-functionalized mesoporous activated carbon].

PubMed

Li, Kun-Quan; Wang, Yan-Jin; Yang, Mei-Rong; Zhu, Zhi-Qiang; Zheng, Zheng

2014-08-01

Bagasse mesoporous carbon was prepared by microwave assisted H3 PO4 activation. Amido and imido groups were modified with ethanediamine on the channels' surface of mesoporous carbon through nitric oxidation and amide reaction. The influence of Pb(II) concentration, adsorption time on Pb(II) adsorption on the ethanediamine-modified mesoporous carbon (AC-EDA) was investigated. The adsorption kinetics and mechanism were also discussed. The results showed that AC-EDA had a great performance for Pb(II) adsorption, and more than 70% of Pb(II) was adsorbed in 5 minutes. The adsorption amount of Pb(II) on the carbon increased with the increase of solution pH in acidic conditions. It was found that AC-EDA had different binding energies on different adsorption sites for Pb(II) separation. The Pb(II) adsorption process on AC-EDA was controlled by intra-particle diffusion in the first 3 min, and then film diffusion played the important pole on the adsorption. The adsorption amount increased with the increase of temperature, indicating the adsorption was an endothermic reaction. The high adsorption energy (> 11 kJ x mol(-1)) implied that the) adsorption was a chemical adsorption. The XPS of AC-EDA before and after Pb(II) adsorption showed that the polyamine group was involved in the adsorption, and should be a main factor of the high efficient adsorption.
sRAGE attenuates angiotensin II-induced cardiomyocyte hypertrophy by inhibiting RAGE-NFκB-NLRP3 activation.

PubMed

Lim, Soyeon; Lee, Myung Eun; Jeong, Jisu; Lee, Jiye; Cho, Soyoung; Seo, Miran; Park, Sungha

2018-05-23

The receptor for advanced glycation endproducts (RAGE) is an innate immunity receptor that has been implicated in the pathogenesis of atherosclerotic cardiovascular disease. However, the possibility that RAGE-mediated signaling is involved in angiotensin II (Ang II)-induced cardiac left ventricular hypertrophy has yet to be investigated. We therefore determined whether RAGE has a role in regulating pathological cardiac hypertrophy. Protein abundance was estimated using Western blotting and intracellular ROS level and phospho-p65 were detected using fluorescence microscopy. Enzyme-linked immunosorbent assay was used to detect HMGB1 and IL-1β. All in vitro experiments were performed using H9C2 cells. To induce cardiomyocyte hypertrophy, 300 nM Ang II was treated for 48 h and 2 µg/ml sRAGE was treated 1 h prior to addition of Ang II. sRAGE attenuated Ang II-induced cardiomyocyte hypertrophy by downregulating RAGE and angiotensin II type 1 receptor expression. Secretion levels of high motility group box 1 and interleukin-1β, estimated from a cell culture medium, were significantly reduced by sRAGE. Activated PKCs and ERK1/2, important signals in left ventricular hypertrophy (LVH) development, were downregulated by sRAGE treatment. Furthermore, we found that nuclear factor-κB and NOD-like receptor protein 3 (NLRP3) were associated with RAGE-mediated cardiomyocyte hypertrophy. In the context of these results, we conclude that RAGE induces cardiac hypertrophy through the activation of the PKCs-ERK1/2 and NF-κB-NLRP3-IL1β signaling pathway, and suggest that RAGE-NLRP3 may be an important mediator of Ang II-induced cardiomyocyte hypertrophy. In addition, we determined that inhibition of RAGE activation with soluble RAGE (sRAGE) has a protective effect on Ang II-induced cardiomyocyte hypertrophy.
Non-enzymatic glycation reduces heparin cofactor II anti-thrombin activity.

PubMed

Ceriello, A; Marchi, E; Barbanti, M; Milani, M R; Giugliano, D; Quatraro, A; Lefebvre, P

1990-04-01

The effects of non-enzymatic glycation on heparin cofactor II activity, at glucose concentrations which might be expected in physiological or diabetic conditions have been evaluated in this study. Radiolabelled glucose incorporation was associated with a loss of heparin cofactor anti-thrombin activity. The heparin cofactor heparin and dermatan sulfate-dependent inhibition of thrombin was significantly reduced, showing a remarkable decrease of the maximum second order rate constant. This study shows that heparin cofactor can be glycated at glucose concentrations found in the blood, and that this phenomenon produces a loss of heparin cofactor-antithrombin activity. These data suggest, furthermore, a possible link between heparin cofactor glycation and the pathogenesis of thrombosis in diabetes mellitus.
pH-dependent interaction of rhodopsin with cyanidin-3-glucoside. 2. Functional aspects.

PubMed

Tirupula, Kalyan C; Balem, Fernanda; Yanamala, Naveena; Klein-Seetharaman, Judith

2009-01-01

Anthocyanins are a class of phytochemicals that confer color to flowers, fruits, vegetables and leaves. They are part of our regular diet and serve as dietary supplements because of numerous health benefits, including improved vision. Recent studies have shown that the anthocyanin cyanidin-3-O-glucoside (C3G) increased regeneration of the dim-light photoreceptor rhodopsin (Matsumoto et al. [2003] J. Agric. Food Chem., 51, 3560-3563). In an accompanying study (Yanamala et al. [2009] Photochem. Photobiol.), we show that C3G directly binds to rhodopsin in a pH-dependent manner. In this study, we investigated the functional consequences of C3G binding to rhodopsin. As observed previously in rod outer segments, regeneration of purified rhodopsin in detergent micelles is also accelerated in the presence of C3G. Thermal denaturation and stability studies using circular dichroism, fluorescence and UV/visible absorbance spectroscopy show that C3G exerts a destabilizing effect on rhodopsin structure while it only modestly alters G-protein activation and the rates at which the light-activated Metarhodopsin II state decays to opsin and free retinal. These results indicate that the mechanism of C3G-enhanced regeneration may be based on changes in opsin structure promoting access to the retinal binding pocket.
The facile synthesis of a chitosan Cu(II) complex by solution plasma process and evaluation of their antioxidant activities.

PubMed

Ma, Fengming; Li, Pu; Zhang, Baiqing; Wang, Zhenyu

2017-10-01

Synthesis of chitosan-Cu(II) complex by solution plasma process (SPP) irradiation was investigated. The effects of the distance between the electrodes, initial Cu(II) concentration, and initial pH on the Cu(II) adsorption capacity were evaluated. The results showed that narrower distance between the electrodes, higher initial Cu(II) concentration and higher initial pH (at pH<6) were favourable for the adsorption capacity of Cu(II). Characterization of the chitosan-Cu(II) complex by ultraviolet-visible (UV-vis), fourier transform infrared (FT-IR) and electron spin resonance (ESR) spectroscopy revealed that the main structure of chitosan was not changed after irradiation. Thermogravimetry (TG) analysis indicated that Cu(II) ions were well incorporated into the chitosan. The antioxidant activity of the chitosan-Cu(II) complex was evaluated by DPPH, ABTS, and reducing power assays. The chitosan-Cu(II) complex exhibited greater antioxidant activity than the original chitosan. Thus, SPP could be used for preparation of chitosan-Cu(II) complexes. Copyright © 2017. Published by Elsevier B.V.
Antibacterial activity of Pd(II) complexes with salicylaldehyde-amino acids Schiff bases ligands.

PubMed

Rîmbu, Cristina; Danac, Ramona; Pui, Aurel

2014-01-01

Palladium(II) complexes with Schiff bases ligands derived from salicylaldehyde and amino acids (Ala, Gly, Met, Ser, Val) have been synthesized and characterized by Fourier transform (FT)-IR, UV-Vis and (1)H-NMR spectroscopy. The electrospray mass spectrometry (ES-MS) spectrometry confirms the formation of palladium(II) complexes in 1/2 (M/L) molar ratio. All the Pd(II) complexes 1, [Pd(SalAla)2]Cl2; 2, [Pd(SalGly)2]Cl2; 3, [Pd(SalMet)2]Cl2; 4, [Pd(SalSer)2]Cl2; 5, [Pd(SalVal)2]Cl2; have shown antibacterial activity against Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Escherichia coli.
Responses of crayfish photoreceptor cells following intense light adaptation.

PubMed

Cummins, D R; Goldsmith, T H

1986-01-01

After intense orange adapting exposures that convert 80% of the rhodopsin in the eye to metarhodopsin, rhabdoms become covered with accessory pigment and appear to lose some microvillar order. Only after a delay of hours or even days is the metarhodopsin replaced by rhodopsin (Cronin and Goldsmith 1984). After 24 h of dark adaptation, when there has been little recovery of visual pigment, the photoreceptor cells have normal resting potentials and input resistances, and the reversal potential of the light response is 10-15 mV (inside positive), unchanged from controls. The log V vs log I curve is shifted about 0.6 log units to the right on the energy axis, quantitatively consistent with the decrease in the probability of quantum catch expected from the lowered concentration of rhodopsin in the rhabdoms. Furthermore, at 24 h the photoreceptors exhibit a broader spectral sensitivity than controls, which is also expected from accumulations of metarhodopsin in the rhabdoms. In three other respects, however, the transduction process appears to be light adapted: The voltage responses are more phasic than those of control photoreceptors. The relatively larger effect (compared to controls) of low extracellular Ca++ (1 mmol/l EGTA) in potentiating the photoresponses suggests that the photoreceptors may have elevated levels of free cytoplasmic Ca++. The saturating depolarization is only about 30% as large as the maximal receptor potentials of contralateral, dark controls, and by that measure the log V-log I curve is shifted downward by 0.54 log units.(ABSTRACT TRUNCATED AT 250 WORDS)
Studies on Some Biologically Cobalt(II), Copper(II) and Zinc(II) Complexes With ONO, NNO and SNO Donor Pyrazinoylhydrazine-Derived Ligands

PubMed Central

Praveen, Marapaka; Sherazi, Syed K. A.

1998-01-01

Biologically active complexes of Co(II), Ni(II), Cu(II) and Zn(II) with novel ONO, NNO and SNO donor pyrazinoylhydrazine-derived compounds have been prepared and characterized on the basis of analytical data and various physicochemical studies. Distorted octahedral structures for all the complexes have been proposed. The synthesized ligands and their complexes have been screened for their antibacterial activity against bacterial species Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella pneumonae. The activity data show the metal complexes to be more active than the parent free ligands against one or more bacterial species. PMID:18475857
Role of H2O2 in hypertension, renin-angiotensin system activation and renal medullary disfunction caused by angiotensin II

PubMed Central

Sousa, T; Oliveira, S; Afonso, J; Morato, M; Patinha, D; Fraga, S; Carvalho, F; Albino-Teixeira, A

2012-01-01

BACKGROUND AND PURPOSE Activation of the intrarenal renin-angiotensin system (RAS) and increased renal medullary hydrogen peroxide (H2O2) contribute to hypertension. We examined whether H2O2 mediated hypertension and intrarenal RAS activation induced by angiotensin II (Ang II). EXPERIMENTAL APPROACH Ang II (200 ng·kg−1·min−1) or saline were infused in Sprague Dawley rats from day 0 to day 14. Polyethylene glycol (PEG)-catalase (10 000 U·kg−1·day−1) was given to Ang II-treated rats, from day 7 to day 14. Systolic blood pressure was measured throughout the study. H2O2, angiotensin AT1 receptor and Nox4 expression and nuclear factor-κB (NF-κB) activation were evaluated in the kidney. Plasma and urinary H2O2 and angiotensinogen were also measured. KEY RESULTS Ang II increased H2O2, AT1 receptor and Nox4 expression and NF-κB activation in the renal medulla, but not in the cortex. Ang II raised plasma and urinary H2O2 levels, increased urinary angiotensinogen but reduced plasma angiotensinogen. PEG-catalase had a short-term antihypertensive effect and transiently suppressed urinary angiotensinogen. PEG-catalase decreased renal medullary expression of AT1 receptors and Nox4 in Ang II-infused rats. Renal medullary NF-κB activation was correlated with local H2O2 levels and urinary angiotensinogen excretion. Loss of antihypertensive efficacy was associated with an eightfold increase of plasma angiotensinogen. CONCLUSIONS AND IMPLICATIONS The renal medulla is a major target for Ang II-induced redox dysfunction. H2O2 appears to be the key mediator enhancing intrarenal RAS activation and decreasing systemic RAS activity. The specific control of renal medullary H2O2 levels may provide future grounds for the treatment of hypertension. PMID:22452317
Rapid activity-induced transcription of arc and other IEGs relies on poised RNA polymerase II

PubMed Central

Saha, Ramendra N.; Wissink, Erin M.; Bailey, Emma R.; Zhao, Meilan; Fargo, David C.; Hwang, Ji-yeon; Daigle, Kelly R.; Fenn, J. Daniel; Adelman, Karen; Dudek, Serena M.

2011-01-01

Summary Transcription of immediate early genes (IEGs) in neurons is exquisitely sensitive to neuronal activity, but the mechanism underlying these early transcription events is largely unknown. We demonstrate that several IEGs such as arc/arg3.1 are poised for near-instantaneous transcription by the stalling of RNA Polymerase II (Pol II) just downstream of the transcription start site in rat neurons. RNAi-depletion of Negative Elongation Factor, a mediator of Pol II stalling, reduces the Pol II occupancy of the arc promoter and compromises the rapid induction of arc and other IEGs. In contrast, reduction of Pol II stalling did not prevent transcription of IEGs that are expressed later and largely lack promoter proximal Pol II stalling. Together, our data strongly indicate that rapid induction of neuronal IEGs requires poised Pol II and suggest a role for this mechanism in a wide variety of transcription-dependent processes, including learning and memory. PMID:21623364
Signaling States of Rhodopsin in Rod Disk Membranes Lacking Transducin βγ-Complex

PubMed Central

Lomonosova, Elena; Kolesnikov, Alexander V.; Kefalov, Vladimir J.

2012-01-01

Purpose. To characterize the possible role of transducin Gtβγ-complex in modulating the signaling properties of photoactivated rhodopsin and its lifetime in rod disc membranes and intact rods. Methods. Rhodopsin photolysis was studied using UV-visible spectroscopy and rapid scanning spectroscopy in the presence of hydroxylamine in highly purified wild-type and Gtγ-deficient mouse rod disc membranes. Complex formation between photoactivated rhodopsin and transducin was measured by extra-metarhodopsin (meta) II assay. Recovery of dark current and flash sensitivity in individual intact wild-type and Gtγ-deficient mouse rods was measured by single-cell suction recordings. Results. Photoconversion of rhodopsin to meta I/meta II equilibrium proceeds normally after elimination of the Gtβγ-complex. The meta I/meta II ratio, the rate of meta II decay, the reactivity of meta II toward hydroxylamine, and the rate of meta III formation in Gtγ-deficient rod disc membranes were identical with those observed in wild-type samples. Under low-intensity illumination, the amount of extra–meta II in Gtγ-deficient discs was significantly reduced. The initial rate of dark current recovery after 12% rhodopsin bleach was three times faster in Gtγ-deficient rods, whereas the rate of the late current recovery was largely unchanged. Mutant rods also exhibited faster postbleach recovery of flash sensitivity. Conclusions. Photoactivation and thermal decay of rhodopsin proceed similarly in wild-type and Gtγ-deficient mouse rods, but the complex formation between photoactivated rhodopsin and transducin is severely compromised in the absence of Gtβγ. The resultant lower transduction activation contributes to faster photoresponse recovery after a moderate pigment bleach in Gtγ-deficient rods. PMID:22266510
Age dependence of pilocarpine-induced status epilepticus and inhibition of CaM kinase II activity in the rat.

PubMed

Singleton, Michael W; Holbert, William H; Ryan, Matthew L; Lee, Anh Tuyet; Kurz, Jonathan E; Churn, Severn B

2005-04-21

This study was conducted to characterize the post-pubertal developmental aspects on seizure susceptibility and severity as well as calcium/calmodulin protein kinase type II (CaM kinase II) activity in status epilepticus (SE). Thirty- to ninety-day-old rats, in 10-day increments, were studied. This corresponds to a developmental age group that has not received thorough attention. The pilocarpine model of SE was characterized both behaviorally and electrographically. Seven criteria were analyzed for electrographical characterization: seizure severity, SE susceptibility, the average number of discrete seizures, average time until first seizure, average time to SE, average time from first discrete seizure to SE, and death. After 1 h of SE, specific brain regions were isolated for biochemical study. Phosphate incorporation into a CaM kinase II-specific substrate, autocamtide III, was used to determine kinase activity. There was no developmental effect on the average number of discrete seizures, average time until first seizure, average time to SE, average time from first discrete seizure to SE, and death; however, there was a significant effect on SE probability and seizure severity. Once SE was expressed, all animals showed a decrease in both cortical and hippocampal CaM kinase II activities. Conversely, seizure activity in the absence of SE did not result in a decrease in CaM kinase II activity. The data suggest that there is a gradual age-dependent modulation of SE susceptibility and seizure severity within the developmental stages studied. Additionally, once status epilepticus is observed at any age, there is a corresponding SE-induced inhibition of CaM kinase II.
Heat-shock-specific phosphorylation and transcriptional activity of RNA polymerase II.

PubMed

Egyházi, E; Ossoinak, A; Lee, J M; Greenleaf, A L; Mäkelä, T P; Pigon, A

1998-07-10

The carboxyl-terminal domain (CTD) of the largest RNA polymerase II (pol II) subunit is a target for extensive phosphorylation in vivo. Using in vitro kinase assays it was found that several different protein kinases can phosphorylate the CTD including the transcription factor IIH-associated CDK-activating CDK7 kinase (R. Roy, J. P. Adamczewski, T. Seroz, W. Vermeulen, J. P. Tassan, L. Schaeffer, E. A. Nigg, J. H. Hoeijmakers, and J. M. Egly, 1994, Cell 79, 1093-1101). Here we report the colocalization of CDK7 and the phosphorylated form of CTD (phosphoCTD) to actively transcribing genes in intact salivary gland cells of Chironomus tentans. Following a heat-shock treatment, both CDK7 and pol II staining disappear from non-heat-shock genes concomitantly with the abolishment of transcriptional activity of these genes. In contrast, the actively transcribing heat-shock genes, manifested as chromosomal puff 5C on chromosome IV (IV-5C), stain intensely for phosphoCTD, but are devoid of CDK7. Furthermore, the staining of puff IV-5C with anti-PCTD antibodies was not detectably influenced by the TFIIH kinase and transcription inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB). Following heat-shock treatment, the transcription of non-heat-shock genes was completely eliminated, while newly formed heat-shock gene transcripts emerged in a DRB-resistant manner. Thus, heat shock in these cells induces a rapid clearance of CDK7 from the non-heat-shock genes, indicating a lack of involvement of CDK7 in the induction and function of the heat-induced genes. The results taken together suggest the existence of heat-shock-specific CTD phosphorylation in living cells. This phosphorylation is resistant to DRB treatment, suggesting that not only phosphorylation but also transcription of heat-shock genes is DRB resistant and that CDK7 in heat shock cells is not associated with TFIIH.
Spectral characterization, cyclic voltammetry, morphology, biological activities and DNA cleaving studies of amino acid Schiff base metal(II) complexes

NASA Astrophysics Data System (ADS)

Neelakantan, M. A.; Rusalraj, F.; Dharmaraja, J.; Johnsonraja, S.; Jeyakumar, T.; Sankaranarayana Pillai, M.

2008-12-01

Metal complexes are synthesized with Schiff bases derived from o-phthalaldehyde (opa) and amino acids viz., glycine (gly) L-alanine (ala), L-phenylalanine (pal). Metal ions coordinate in a tetradentate or hexadentate manner with these N 2O 2 donor ligands, which are characterized by elemental analysis, molar conductance, magnetic moments, IR, electronic, 1H NMR and EPR spectral studies. The elemental analysis suggests the stoichiometry to be 1:1 (metal:ligand). Based on EPR studies, spin-Hamiltonian and bonding parameters have been calculated. The g-values calculated for copper complexes at 300 K and in frozen DMSO (77 K) indicate the presence of the unpaired electron in the d orbital. The evaluated metal-ligand bonding parameters showed strong in-plane σ- and π-bonding. X-ray diffraction (XRD) and scanning electron micrography (SEM) analysis provide the crystalline nature and the morphology of the metal complexes. The cyclic voltammograms of the Cu(II)/Mn(II)/VO(II) complexes investigated in DMSO solution exhibit metal centered electroactivity in the potential range -1.5 to +1.5 V. The electrochemical data obtained for Cu(II) complexes explains the change of structural arrangement of the ligand around Cu(II) ions. The biological activity of the complexes has been tested on eight bacteria and three fungi. Cu(II) and Ni(II) complexes show an increased activity in comparison to the controls. The metal complexes of opapal Schiff base were evaluated for their DNA cleaving activities with calf-thymus DNA (CT DNA) under aerobic conditions. Cu(II) and VO(II) complexes show more pronounced activity in presence of the oxidant.

20 CFR 404.1321 - Ninety-day active service requirement for post-World War II veterans.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Ninety-day active service requirement for post-World War II veterans. 404.1321 Section 404.1321 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Wage Credits for Veterans and Members of the Uniformed Services Post-World War II...
Chitosan-Copper (II) complex as antibacterial agent: synthesis, characterization and coordinating bond- activity correlation study

NASA Astrophysics Data System (ADS)

Mekahlia, S.; Bouzid, B.

2009-11-01

The antimicrobial activity of chitosan is unstable and sensitive to many factors such as molecular weight. Recent investigations showed that low molecular weight chitosan exhibited strong bactericidal activities compared to chitosan with high molecular weight. Since chitosan degradation can be caused by the coordinating bond, we attempt to synthesize and characterize the chitosan-Cu (II) complex, and thereafter study the coordinating bond effect on its antibacterial activity against Salmonella enteritidis. Seven chitosan-copper complexes with different copper contents were prepared and characterized by FT-IR, UV-vis, XRD and atomic absorption spectrophotometry (AAS). Results indicated that for chitosan-Cu (II) complexes with molar ratio close to 1:1, the inhibition rate reached 100%.
VizieR Online Data Catalog: Excess CaII H&K emission in active binaries (Montes+, 1996)

NASA Astrophysics Data System (ADS)

Montes, D.; Fernandez-Figueroa, M. J.; Cornide, M.; de Castro, E.

1996-05-01

In this work we analyze the behaviour of the excess CaII H & K and H_epsilon emissions in a sample of 73 chromospherically active binary systems (RS CVn and BY Dra classes), of different activity levels and luminosity classes. This sample includes the 53 stars analyzed by Fernandez-Figueroa et al. (1994) and the observations of 28 systems described by Montes et al. (1995). By using the spectral subtraction technique (subtraction of a synthesized stellar spectrum constructed from reference stars of spectral type and luminosity class similar to those of the binary star components) we obtain the active-chromosphere contribution to the CaII H & K lines in these 73 systems. We have determined the excess CaII H & K emission equivalent widths and converted them into surface fluxes. The emissions arising from each component were obtained when it was possible to deblend both contributions. (4 data files).
The brown algae Pl.LSU/2 group II intron-encoded protein has functional reverse transcriptase and maturase activities.

PubMed

Zerbato, Madeleine; Holic, Nathalie; Moniot-Frin, Sophie; Ingrao, Dina; Galy, Anne; Perea, Javier

2013-01-01

Group II introns are self-splicing mobile elements found in prokaryotes and eukaryotic organelles. These introns propagate by homing into precise genomic locations, following assembly of a ribonucleoprotein complex containing the intron-encoded protein (IEP) and the spliced intron RNA. Engineered group II introns are now commonly used tools for targeted genomic modifications in prokaryotes but not in eukaryotes. We speculate that the catalytic activation of currently known group II introns is limited in eukaryotic cells. The brown algae Pylaiella littoralis Pl.LSU/2 group II intron is uniquely capable of in vitro ribozyme activity at physiological level of magnesium but this intron remains poorly characterized. We purified and characterized recombinant Pl.LSU/2 IEP. Unlike most IEPs, Pl.LSU/2 IEP displayed a reverse transcriptase activity without intronic RNA. The Pl.LSU/2 intron could be engineered to splice accurately in Saccharomyces cerevisiae and splicing efficiency was increased by the maturase activity of the IEP. However, spliced transcripts were not expressed. Furthermore, intron splicing was not detected in human cells. While further tool development is needed, these data provide the first functional characterization of the PI.LSU/2 IEP and the first evidence that the Pl.LSU/2 group II intron splicing occurs in vivo in eukaryotes in an IEP-dependent manner.
The Brown Algae Pl.LSU/2 Group II Intron-Encoded Protein Has Functional Reverse Transcriptase and Maturase Activities

PubMed Central

Zerbato, Madeleine; Holic, Nathalie; Moniot-Frin, Sophie; Ingrao, Dina; Galy, Anne; Perea, Javier

2013-01-01

Group II introns are self-splicing mobile elements found in prokaryotes and eukaryotic organelles. These introns propagate by homing into precise genomic locations, following assembly of a ribonucleoprotein complex containing the intron-encoded protein (IEP) and the spliced intron RNA. Engineered group II introns are now commonly used tools for targeted genomic modifications in prokaryotes but not in eukaryotes. We speculate that the catalytic activation of currently known group II introns is limited in eukaryotic cells. The brown algae Pylaiella littoralis Pl.LSU/2 group II intron is uniquely capable of in vitro ribozyme activity at physiological level of magnesium but this intron remains poorly characterized. We purified and characterized recombinant Pl.LSU/2 IEP. Unlike most IEPs, Pl.LSU/2 IEP displayed a reverse transcriptase activity without intronic RNA. The Pl.LSU/2 intron could be engineered to splice accurately in Saccharomyces cerevisiae and splicing efficiency was increased by the maturase activity of the IEP. However, spliced transcripts were not expressed. Furthermore, intron splicing was not detected in human cells. While further tool development is needed, these data provide the first functional characterization of the PI.LSU/2 IEP and the first evidence that the Pl.LSU/2 group II intron splicing occurs in vivo in eukaryotes in an IEP-dependent manner. PMID:23505475
Regulation of succinate-ubiquinone reductase and fumarate reductase activities in human complex II by phosphorylation of its flavoprotein subunit.

PubMed

Tomitsuka, Eriko; Kita, Kiyoshi; Esumi, Hiroyasu

2009-01-01

Complex II (succinate-ubiquinone reductase; SQR) is a mitochondrial respiratory chain enzyme that is directly involved in the TCA cycle. Complex II exerts a reverse reaction, fumarate reductase (FRD) activity, in various species such as bacteria, parasitic helminths and shellfish, but the existence of FRD activity in humans has not been previously reported. Here, we describe the detection of FRD activity in human cancer cells. The activity level was low, but distinct, and it increased significantly when the cells were cultured under hypoxic and glucose-deprived conditions. Treatment with phosphatase caused the dephosphorylation of flavoprotein subunit (Fp) with a concomitant increase in SQR activity, whereas FRD activity decreased. On the other hand, treatment with protein kinase caused an increase in FRD activity and a decrease in SQR activity. These data suggest that modification of the Fp subunit regulates both the SQR and FRD activities of complex II and that the phosphorylation of Fp might be important for maintaining mitochondrial energy metabolism within the tumor microenvironment.
The One Micron Fe II Lines in Active Galaxies and Emission Line Stars

NASA Astrophysics Data System (ADS)

Rudy, R. J.; Mazuk, S.; Puetter, R. C.; Hamann, F. W.

1999-05-01

The infrared multiplet of Fe II lines at 0.9997, 1.0501, 1.0863, and 1.1126 microns are particularly strong relative to other red and infrared Fe II features. They reach their greatest strength, relative to the hydrogen lines, in the Seyfert 1 galaxy I Zw 1, and are a common, although not ubiquitous feature, in the broad line regions of active galaxies. In addition, they are seen in a diverse assortment of Galactic sources including young stars, Herbig Ae and Be stars, luminous blue variables, proto-planetary nebulae, and symbiotic novae. They are probably excited by Lyman alpha florescence but the exact path of the cascade to their upper levels is uncertain. They arise in dense, sheltered regions of low ionization and are frequently observed together with the infrared Ca II triplet and the Lyman beta excited O I lines 8446 and 11287. The strengths of the four Fe II features, relative to each other, are nearly constant from object to object suggesting a statistical population of their common upper multiplet. Their intensities, in comparison to the Paschen lines, indicate that they can be important coolants for regions with high optical depths in the hydrogen lines. In addition to I Zw 1 and other active galaxies, we present spectra for the Galactic sources MWC 17, MWC 84, MWC 340, MWC 922, PU Vul, and M 1-92. We review the status of the Fe II observations and discuss the excitation process and possible implications. This work was supported by the IR&D program of the Aerospace Corporation. RCP and FWH acknowledge support from NASA.
Adsorption of Cu(II) Ions in Aqueous Solutions by HCl Activated Carbon of Oil Palm

NASA Astrophysics Data System (ADS)

Muslim, A.; Syamsuddin, Y.; Salamun, A.; Abubakar; Ramadhan, D.; Peiono, D.

2017-06-01

Activated carbon was prepared from oil palm empty fruit bunch (OPEFB) by pyrolysis at 873.15 K in a furnace and chemical activation using 0.01 M HCl. Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy and BET (Brunauer, Emmett and Teller) surface area analyses were taken into account to investigate the chemical functional group, to characterise the surface morphology and to determine total surface area the OPEFB AC, respectively. Experiments in batch mode were conducted to investigate Cu(II) adsorption capacity by the OPEFB AC whereas the system consisted of 1 g the OPEFB AC in 100 mL Cu(II) aqueous solution with initial concentration in the range of 10-70 mg/L, magnetic stirring at 75 rpm, room temperature of 300.15 K (± 2 K), at 1 atm and neutral pH over contact time in the range of 0-150 min. As the result, Cu(II) adsorption capacity increased exponentially over contact time and initial concentration. The Cu(II) adsorption kinetics followed the pseudo second order kinetics with the correlation coefficients (R 2), kinetics rate constant and equilibrium adsorption capacity being 0.98, 4.81 mg/g and 0.15/min, respectively for initial Cu(II) concentration being 58.71 mg/L. In addition, Cu(II) adsorption isotherm followed the Langmuir equation with the R2 value, the mono-layer and over-all adsorption capacity being 0.99, 5.92 mg/g and 0.17 L/mg, respectively.
Synthesis, spectral, thermal and antimicrobial studies on cobalt(II), nickel(II), copper(II), zinc(II) and palladium(II) complexes containing thiosemicarbazone ligand

NASA Astrophysics Data System (ADS)

El-Sawaf, Ayman K.; El-Essawy, Farag; Nassar, Amal A.; El-Samanody, El-Sayed A.

2018-04-01

The coordination characteristic of new N4-morpholinyl isatin-3-thiosemicarbazone (HL) towards Co(II), Ni(II), Cu(II), Zn(II) and Pd(II) has been studies. The structures of the complexes were described by elemental analyses, molar conductivity, magnetic, thermal and spectral (IR, UV-Vis, 1H and 13C NMR and ESR) studies. On the basis of analytical and spectral studies the ligand behaves as monobasic tridentate ONS donor forming two five membered rings towards cobalt, copper and palladium and afforded complexes of the kind [M(L)X], (Mdbnd Co, Cu or Pd; Xdbnd Cl, Br or OAc). Whereas the ligand bound to NiCl2 as neutral tridentate ONS donor and with ZnCl2 as neutral bidentate NS donor. The newly synthesized thiosemicarbazone ligand and some of its complexes were examined for antimicrobial activity against 2 gram negative bacterial strains (Escherichia coli Pseudomonas and aeruginosa), 2 gram positive bacterial strains (Streptococcus pneumoniae and Staphylococcus aureus)} and two Pathogenic fungi (Aspergillus fumigatus and Candida albicans). All metal complexes possess higher antimicrobial activity comparing with the free thiosemicarbazone ligand. The high potent activities of the complexes may arise from the coordination and chelation, which tends to make metal complexes act as more controlling and potent antimicrobial agents, thus hindering the growing of the microorganisms. The antimicrobial results also show that copper bromide complex is better antimicrobial agent as compared to the Schiff base and its metal complexes.
Synthesis, characterization and biological activity of complexes of 2-hydroxy-3,5-dimethylacetophenoneoxime (HDMAOX) with copper(II), cobalt(II), nickel(II) and palladium(II)

NASA Astrophysics Data System (ADS)

Singh, Bibhesh K.; Jetley, Umesh K.; Sharma, Rakesh K.; Garg, Bhagwan S.

2007-09-01

A new series of complexes of 2-hydroxy-3,5-dimethyl acetophenone oxime (HDMAOX) with Cu(II), Co(II), Ni(II) and Pd(II) have been prepared and characterized by different physical techniques. Infrared spectra of the complexes indicate deprotonation and coordination of the phenolic OH. It also confirms that nitrogen atom of the oximino group contributes to the complexation. Electronic spectra and magnetic susceptibility measurements reveal square planar geometry for Cu(II), Ni(II) and Pd(II) complexes and tetrahedral geometry for Co(II) complex. The elemental analyses and mass spectral data have justified the ML 2 composition of complexes. Kinetic and thermodynamic parameters were computed from the thermal decomposition data using Coats and Redfern method. The geometry of the metal complexes has been optimized with the help of molecular modeling. The free ligand (HDMAOX) and its metal complexes have been tested in vitro against Alternarie alternate, Aspergillus flavus, Aspergillus nidulans and Aspergillus niger fungi and Streptococcus, Staph, Staphylococcus and Escherchia coli bacteria in order to assess their antimicrobial potential. The results indicate that the ligand and its metal complexes possess antimicrobial properties.
Synthesis, characterization and biological activity of complexes of 2-hydroxy-3,5-dimethylacetophenoneoxime (HDMAOX) with copper(II), cobalt(II), nickel(II) and palladium(II).

PubMed

Singh, Bibhesh K; Jetley, Umesh K; Sharma, Rakesh K; Garg, Bhagwan S

2007-09-01

A new series of complexes of 2-hydroxy-3,5-dimethyl acetophenone oxime (HDMAOX) with Cu(II), Co(II), Ni(II) and Pd(II) have been prepared and characterized by different physical techniques. Infrared spectra of the complexes indicate deprotonation and coordination of the phenolic OH. It also confirms that nitrogen atom of the oximino group contributes to the complexation. Electronic spectra and magnetic susceptibility measurements reveal square planar geometry for Cu(II), Ni(II) and Pd(II) complexes and tetrahedral geometry for Co(II) complex. The elemental analyses and mass spectral data have justified the ML(2) composition of complexes. Kinetic and thermodynamic parameters were computed from the thermal decomposition data using Coats and Redfern method. The geometry of the metal complexes has been optimized with the help of molecular modeling. The free ligand (HDMAOX) and its metal complexes have been tested in vitro against Alternarie alternate, Aspergillus flavus, Aspergillus nidulans and Aspergillus niger fungi and Streptococcus, Staph, Staphylococcus and Escherchia coli bacteria in order to assess their antimicrobial potential. The results indicate that the ligand and its metal complexes possess antimicrobial properties.
Active site of tripeptidyl peptidase II from human erythrocytes is of the subtilisin type

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomkinson, B.; Wernstedt, C.; Hellman, U.

1987-11-01

The present report presents evidence that the amino acid sequence around the serine of the active site of human tripeptidyl peptidase II is of the subtilisin type. The enzyme from human erythrocytes was covalently labeled at its active site with (/sup 3/H)diisopropyl fluorophosphate, and the protein was subsequently reduced, alkylated, and digested with trypsin. The labeled tryptic peptides were purified by gel filtration and repeated reversed-phase HPLC, and their amino-terminal sequences were determined. Residue 9 contained the radioactive label and was, therefore, considered to be the active serine residue. The primary structure of the part of the active site (residuesmore » 1-10) containing this residue was concluded to be Xaa-Thr-Gln-Leu-Met-Asx-Gly-Thr-Ser-Met. This amino acid sequence is homologous to the sequence surrounding the active serine of the microbial peptidases subtilisin and thermitase. These data demonstrate that human tripeptidyl peptidase II represents a potentially distinct class of human peptidases and raise the question of an evolutionary relationship between the active site of a mammalian peptidase and that of the subtilisin family of serine peptidases.« less
Active site of tripeptidyl peptidase II from human erythrocytes is of the subtilisin type.

PubMed Central

Tomkinson, B; Wernstedt, C; Hellman, U; Zetterqvist, O

1987-01-01

The present report presents evidence that the amino acid sequence around the serine of the active site of human tripeptidyl peptidase II is of the subtilisin type. The enzyme from human erythrocytes was covalently labeled at its active site with [3H]diisopropyl fluorophosphate, and the protein was subsequently reduced, alkylated, and digested with trypsin. The labeled tryptic peptides were purified by gel filtration and repeated reversed-phase HPLC, and their amino-terminal sequences were determined. Residue 9 contained the radioactive label and was, therefore, considered to be the active serine residue. The primary structure of the part of the active site (residues 1-10) containing this residue was concluded to be Xaa-Thr-Gln-Leu-Met-Asx-Gly-Thr-Ser-Met. This amino acid sequence is homologous to the sequence surrounding the active serine of the microbial peptidases subtilisin and thermitase. These data demonstrate that human tripeptidyl peptidase II represents a potentially distinct class of human peptidases and raise the question of an evolutionary relationship between the active site of a mammalian peptidase and that of the subtilisin family of serine peptidases. PMID:3313395
[Evaluation of serum PIVKA-II by Lumipulse PrestoII assay].

PubMed

Hiramatsu, Kumiko; Tanaka, Yasuhito; Takagi, Kazumi; Kani, Satomi; Goto, Takaaki; Takasaka, Yoshimitsu; Matsuura, Kentaro; Sugauchi, Fuminaka; Moriyama, Kazushige; Murakami, Hiroshi; Kitajima, Sachiko; Mizokami, Masashi

2009-03-01

Measurements of serum concentrations of Des-gamma-carboxy Prothrombin (PIVKA-II) are widely used for diagnosing hepatocellular carcinoma (HCC). Recently, in Lumipulsef assay, it was reported that antibodies against alkaline phosphatase (ALP) derived from anti bleeding sheets led false high values of PIVKA-II in the patients with HCC resection. To improve the previous issue, newly developed Lumipulse PrestoII assay was examined. (1) The assay was reliable and positively correlated with the previous assays (Lumipulse f and Picolumi, R = 0.997 and 0.994 (n=115), respectively). (2) Eleven cases, which had false high values of PIVKA-II by the Lumipulsef assay, were examined by the PrestoII assay with excess of inactive ALP. The false high values of 10 cases were improved, but only one was still high. False reactivity of this case was stronger than other cases, more effective adsorption was required. (3) Comparing the absorbent activity of inactive ALP among 6 different kinds, we found inactive ALP with much higher adsorbent activity. When this inactive ALP was applied to assay, false high values of PIVKA-II were improved in all 11 cases. In conclusion, the PrestoII assay, which applies the inactive ALP with high activity, is reliable and useful for clinical screening.
FUSE Cycle 3 Program CO22: Chromospheric Activity in Population II Giants

NASA Technical Reports Server (NTRS)

Harper, Graham M.

2004-01-01

One of the mysteries of Population II giants is that they still show chromospheric emission despite their great age. The global dynamo which was active during their main-sequence lifetimes is expected to become extremely weak through magnetic rotational braking. The nature of the observed emission is not understood; although acoustic shock waves might provide the heating, acoustic waves are not predicted to drive the observed mass loss - which in turn requires the dissipation of magneto-hydrodynamic waves. This program was designed to search for the faint stellar H Ly(beta) emission wings and the fluorescent Fe II and H2 emission from one of the brightest, metal poor, Population II stars. These FUSE diagnostics, when combined with existing UV and optical spectra, help determine the major radiative cooling channels for the chromosphere. This observation was to complement that previously planned for the mildly metal deficient giant alpha Boo (K2 III). However, a Boo has yet to be observed with FUSE.
Human type II pneumocyte chemotactic responses to CXCR3 activation are mediated by splice variant A.

PubMed

Ji, Rong; Lee, Clement M; Gonzales, Linda W; Yang, Yi; Aksoy, Mark O; Wang, Ping; Brailoiu, Eugen; Dun, Nae; Hurford, Matthew T; Kelsen, Steven G

2008-06-01

Chemokine receptors control several fundamental cellular processes in both hematopoietic and structural cells, including directed cell movement, i.e., chemotaxis, cell differentiation, and proliferation. We have previously demonstrated that CXCR3, the chemokine receptor expressed by Th1/Tc1 inflammatory cells present in the lung, is also expressed by human airway epithelial cells. In airway epithelial cells, activation of CXCR3 induces airway epithelial cell movement and proliferation, processes that underlie lung repair. The present study examined the expression and function of CXCR3 in human alveolar type II pneumocytes, whose destruction causes emphysema. CXCR3 was present in human fetal and adult type II pneumocytes as assessed by immunocytochemistry, immunohistochemistry, and Western blotting. CXCR3-A and -B splice variant mRNA was present constitutively in cultured type II cells, but levels of CXCR3-B greatly exceeded CXCR3-A mRNA. In cultured type II cells, I-TAC, IP-10, and Mig induced chemotaxis. Overexpression of CXCR3-A in the A549 pneumocyte cell line produced robust chemotactic responses to I-TAC and IP-10. In contrast, I-TAC did not induce chemotactic responses in CXCR3-B and mock-transfected cells. Finally, I-TAC increased cytosolic Ca(2+) and activated the extracellular signal-regulated kinase, p38, and phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B kinases only in CXCR3-A-transfected cells. These data indicate that the CXCR3 receptor is expressed by human type II pneumocytes, and the CXCR3-A splice variant mediates chemotactic responses possibly through Ca(2+) activation of both mitogen-activated protein kinase and PI 3-kinase signaling pathways. Expression of CXCR3 in alveolar epithelial cells may be important in pneumocyte repair from injury.
Synthesis, characterization, DFT calculations and biological studies of Mn(II), Fe(II), Co(II) and Cd(II) complexes based on a tetradentate ONNO donor Schiff base ligand

NASA Astrophysics Data System (ADS)

Abdel-Rahman, Laila H.; Ismail, Nabawia M.; Ismael, Mohamed; Abu-Dief, Ahmed M.; Ahmed, Ebtehal Abdel-Hameed

2017-04-01

This study highlights synthesis and characterization of a tetradentate ONNO Schiff base ligand namely (1, 1‧- (pyridine-2, 3-dimethyliminomethyl) naphthalene-2, 2‧-diol) and hereafter denotes as "HNDAP″ and selected metal complexes including Mn(II), Fe(II), Co(II) and Cd(II) as a central metal. HNDAP was synthesized from 1:2 M ratio condensation of 2, 3-diaminopyridine and 2- hydroxy-1-naphthaldhyde, respectively. The stoichiometric ratios of the prepared complexes were estimated using complementary techniques such as; elemental analyses (-C, H, N), FT-IR, magnetic measurements and molar conductivity. Furthermore, their physicochemical studies were carried out using thermal TGA, DTA and kinetic-thermodynamic studies along with DFT calculations. The results of elemental analyses showed that these complexes are present in a 1:1 metal-to- ligand molar ratio. Moreover, the magnetic susceptibilities values at room temperature revealed that Mn(II), Fe(II) and Co(II) complexes are paramagnetic in nature and have an octahedral (Oh) geometry. In contrast, Cd(II) is diamagnetic and stabilizes in square planar sites. The molar conductivity measurements indicated that all complexes are nonelectrolytes in dimethyl formamide. Spectral data suggested that the ligand is as tetradentate and coordinated with Co(II) ion through two phenolic OH and two azomethine nitrogen. However, for Mn(II), Fe(II) and Cd(II) complexes, the coordination occurred through two phenolic oxygen and two azomethine nitrogen with deprotonation of OH groups. The proposed chemical structures have been validated by quantum mechanics calculations. Antimicrobial activities of both the HNDAP Schiff base ligand and its metal complexes were tested against strains of Gram (-ve) E. coli and Gram (+ve) B. subtilis and S. aureus bacteria and C. albicans, A. flavus and T. rubrum fungi. All the prepared compounds showed good results of inhibition against the selected pathogenic microorganisms. The investigated
Stereochemical control over Mn(II)-Thio versus Mn(II)-Oxy coordination in adenosine 5 prime -O-(1-thiodiphosphate) complexes at the active site of creatine kinase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smithers, G.W.; Sammons, R.D.; Goodhart, P.J.

1989-02-21

The stereochemical configurations of the Mn(II) complexes with the resolved epimers of adenosine 5{prime}-O-(1-thiodiphosphate) (ADP{alpha}S), bound at the active site of creatine kinase, have been determined in order to assess the relative strengths of enzymic stereoselectivity versus Lewis acid/base preferences in metal-ligand binding. Electron paramagnetic resonance (EPR) data have been obtained for Mn(II) in anion-stabilized, dead-end (transition-state analogue) complexes, in ternary enzyme-Mn{sup II}ADP{alpha}S complexes, and in the central complexes of the equilibrium mixture. The modes of coordination of Mn(II) at P{sub alpha} in the nitrate-stabilized, dead-end complexes with each epimer of ADP{alpha}S were ascertained by EPR measurements with (R{sub p})-({alpha}-{supmore » 17}O)ADP{alpha}S and (S{sub p})-({alpha}-{sup 17}O)ADP{alpha}S. A reduction in the magnitude of the {sup 55}Mn hyperfine coupling constant in the spectrum for the complex containing (S{sub p})-ADP{alpha}S is indicative of Mn(II)-thio coordination at P{sub alpha}. The results indicate that a strict discrimination for a unique configuration of the metal-nucleotide substrate is expressed upon binding of all of the substrates to form the active complex (or an analogue thereof). This enzymic stereoselectivity provides sufficient binding energy to overcome an intrinsic preference for the hard Lewis acid Mn(II) to coordinate to the hard Lewis base oxygen.« less
Comparison of Forsus FRD EZ and Andresen activator in the treatment of class II, division 1 malocclusions.

PubMed

Bilgiç, Fundagül; Başaran, Güvenç; Hamamci, Orhan

2015-03-01

Purpose of this study is to evaluate the effects of Forsus Fatigue-Resistant Device (FRD) EZ and Andresen activator in terms of skeletal, dental, and soft tissue changes in actively growing patients presenting with class II, division 1 malocclusion. Study sample included 60 subjects. Inclusion criteria were as follows: class II division 1 malocclusion, retrognathic mandible, normal or low-angle growth pattern, and peak growth period. The first study group consisted of 20 patients who were treated with Forsus appliance, and the second group of 20 patients received treatment with Andresen activator. Control group received no treatment. Our results revealed that both appliances enhanced mandibular growth, helped increase the length of the mandible, and had a restraining growth effect on the maxilla. Anterior face height increased in both of treatment groups, whereas posterior face height had a significant increase in the activator group only. More mandibular incisors protrusion and intrusion were seen with the Forsus appliance. Moreover, occlusal plane and palatal plane rotated significantly in clockwise direction as a result of dentoalveolar changes only in the Forsus group. As well as the Forsus appliances corrected class II discrepancies mostly through dentoalveolar changes as compared to the activator group, both appliances proved effective in the treatment of growing individuals having class II malocclusions with mandibular retrognathia. By this investigation, two treatment methods, which are currently used in clinical practice, will be evaluated, and the results will be useful for clinicians.
High-Energy Activation Simulation Coupling TENDL and SPACS with FISPACT-II

NASA Astrophysics Data System (ADS)

Fleming, Michael; Sublet, Jean-Christophe; Gilbert, Mark

2018-06-01

To address the needs of activation-transmutation simulation in incident-particle fields with energies above a few hundred MeV, the FISPACT-II code has been extended to splice TENDL standard ENDF-6 nuclear data with extended nuclear data forms. The JENDL-2007/HE and HEAD-2009 libraries were processed for FISPACT-II and used to demonstrate the capabilities of the new code version. Tests of the libraries and comparisons against both experimental yield data and the most recent intra-nuclear cascade model results demonstrate that there is need for improved nuclear data libraries up to and above 1 GeV. Simulations on lead targets show that important radionuclides, such as 148Gd, can vary by more than an order of magnitude where more advanced models find agreement within the experimental uncertainties.

Effect of human serum albumin upon the permeabilizing activity of sticholysin II, a pore forming toxin from Stichodactyla heliantus.

PubMed

Celedón, Gloria; González, Gustavo; Gulppi, Felipe; Pazos, Fabiola; Lanio, María E; Alvarez, Carlos; Calderón, Cristian; Montecinos, Rodrigo; Lissi, Eduardo

2013-12-01

Sticholysin II (St II) is a haemolytic toxin isolated from the sea anemone Stichodactyla helianthus. The high haemolytic activity of this toxin is strongly dependent on the red cell status and the macromolecule conformation. In the present communication we evaluate the effect of human serum albumin on St II haemolytic activity and its capacity to form pores in the bilayer of synthetic liposomes. St II retains its pore forming capacity in the presence of large concentrations (up to 500 μM) of human serum albumin. This effect is observed both in its capacity to produce red blood cells haemolysis and to generate functional pores in liposomes. In particular, the capacity of the toxin to lyse red blood cells increases in the presence of human serum albumin (HSA). Regarding the rate of the pore forming process, it is moderately decreased in liposomes and in red blood cells, in spite of an almost total coverage of the interface by albumin. All the data obtained in red cells and model membranes show that St II remains lytically active even in the presence of high HSA concentrations. This stubbornness can explain why the toxin is able to exert its haemolytic activity on membranes immersed in complex plasma matrixes such as those present in living organisms.
Resonance raman spectroscopy of an ultraviolet-sensitive insect rhodopsin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pande, C.; Deng, H.; Rath, P.

1987-11-17

The authors present the first visual pigment resonance Raman spectra from the UV-sensitive eyes of an insect, Ascalaphus macaronius (owlfly). This pigment contains 11-cis-retinal as the chromophore. Raman data have been obtained for the acid metarhodopsin at 10/sup 0/C in both H/sub 2/O and D/sub 2/O. The C=N stretching mode at 1660 cm/sup -1/ in H/sub 2/O shifts to 1631 cm/sup -1/ upon deuteriation of the sample, clearly showing a protonated Schiff base linkage between the chromophore and the protein. The structure-sensitive fingerprint region shows similarities to the all-trans-protonated Schiff base of model retinal chromophores, as well as to themore » octopus acid metarhodopsin and bovine metarhodopsin I. Although spectra measured at -100/sup 0/C with 406.7-nm excitation, to enhance scattering from rhodopsin (lambda/sub max/ 345 nm), contain a significant contribution from a small amount of contaminants (cytochrome(s) and/or accessory pigment) in the sample, the C=N stretch at 1664 cm/sup -1/ suggests a protonated Schiff base linkage between the chromophore and the protein in rhodopsin as well. For comparison, this mode also appears at approx. 1660 cm/sup -1/ in both the vertebrate (bovine) and the invertebrate (octopus) rhodopsins. These data are particularly interesting since the absorption maximum of 345 nm for rhodopsin might be expected to originate from an unprotonated Schiff base linkage. That the Schiff base linkage in the owlfly rhodopsin, like in bovine and in octopus, is protonated suggests that a charged chromophore is essential to visual transduction.« less
Enhanced performance of Zn(II)-doped lead-acid batteries with electrochemical active carbon in negative mass

NASA Astrophysics Data System (ADS)

Xiang, Jiayuan; Hu, Chen; Chen, Liying; Zhang, Dong; Ding, Ping; Chen, Dong; Liu, Hao; Chen, Jian; Wu, Xianzhang; Lai, Xiaokang

2016-10-01

The effect and mechanism of Zn(II) on improving the performances of lead-acid cell with electrochemical active carbon (EAC) in negative mass is investigated. The hydrogen evolution of the cell is significantly reduced due to the deposition of Zn on carbon surface and the increased porosity of negative mass. Zn(II) additives can also improve the low-temperature and high-rate capacities of the cell with EAC in negative mass, which ascribes to the formation of Zn on lead and carbon surface that constructs a conductive bridge among the active mass. Under the co-contribution of EAC and Zn(II), the partial-state-of-charge cycle life is greatly prolonged. EAC optimizes the NAM structure and porosity to enhance the charge acceptance and retard the lead sulfate accumulation. Zn(II) additive reduces the hydrogen evolution during charge process and improves the electric conductivity of the negative electrode. The cell with 0.6 wt% EAC and 0.006 wt% ZnO in negative mass exhibits 90% reversible capacity of the initial capacity after 2100 cycles. In contrast, the cell with 0.6 wt% EAC exhibits 84% reversible capacity after 2100 cycles and the control cell with no EAC and Zn(II) exhibits less than 80% reversible capacity after 1350 cycles.
Synthesis, spectroscopic, molecular structure, antioxidant, antimicrobial and antitumor behavior of Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) complexes of O2N type tridentate chromone-2-carboxaldehyde Schiff's base ligand

NASA Astrophysics Data System (ADS)

Ammar, Reda A.; Alaghaz, Abdel-Nasser M. A.; Zayed, Mohamed E.; Al-Bedair, Lamia A.

2017-08-01

Tridentate Schiff's base (HL) ligand was synthesized via condensation of salicylaldehyde and 3-hydroxypyridin-2-yliminomethyl-4H-chromen-4-one and their corresponding Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) complexes have been synthesized. The isolated solid complexes were characterized by elemental analyses, molar conductance, spectral (IR, UV-Vis, 1H NMR), magnetic moment, EPR, and thermal measurements. The IR spectra showed that HL was coordinated to the metal ions in tridentate manner with O2N donor sites of the azomethine N, deprotonated phenolic-OH and carbonyl-O. The activation of thermodynamic parameters are calculated using Coast-Redfern and Horowitz-Metzger (HM). The octahedral geometry of the complexes is confirmed using DFT method from DMOL3 calculations, UV-Vis and magnetic moment measurements, ESR and ligand field parameters. Antioxidant activities have also been performed for all the compounds. The investigated ligand and metal complexes were screened for their in-vitro antimicrobial activities against different types of fungal and bacterial strains. The resulting data assert on the inspected compounds as a highly promising bactericides and fungicides. The antitumor activities of all inspected compounds were evaluated towards human liver Carcinoma (HepG2) cell line.
Natriuretic peptide receptor-C activation attenuates angiotensin II-induced enhanced oxidative stress and hyperproliferation of aortic vascular smooth muscle cells.

PubMed

Madiraju, Padma; Hossain, Ekhtear; Anand-Srivastava, Madhu B

2018-02-07

We showed previously that natriuretic peptide receptor-C (NPR-C) agonist, C-ANP 4-23 , attenuated the enhanced expression of Giα proteins in vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) through the inhibition of enhanced oxidative stress. Since the enhanced levels of endogenous angiotensin II (Ang II) contribute to the overexpression of Giα proteins and augmented oxidative stress in VSMC from SHR, the present study was undertaken to investigate if C-ANP 4-23 could also attenuate angiotensin II (Ang II)-induced oxidative stress and associated signaling. Ang II treatment of aortic VSMC augmented the levels of superoxide anion (O 2 - ), NADPH oxidase activity, and the expression of NADPH oxidase subunits and C-ANP 4-23 treatment attenuated all these to control levels. In addition, Ang II-induced enhanced levels of thiobarbituric acid-reactive substances (TBARS) and protein carbonyl content were also attenuated toward control levels by C-ANP 4-23 treatment. On the other hand, Ang II inhibited the levels of nitric oxide (NO) and augmented the levels of peroxynitrite (OONO - ) in VSMC which were restored to control levels by C-ANP 4-23 treatment. Furthermore, C-ANP 4-23 treatment attenuated Ang II-induced enhanced expression of Giα proteins, phosphorylation of p38, JNK, and ERK 1,2 as well as hyperproliferation of VSMC as determined by DNA synthesis, and metabolic activity. These results indicate that C-ANP 4-23 , via the activation of NPR-C, attenuates Ang II-induced enhanced nitroxidative stress, overexpression of Giα proteins, increased activation of the p38/JNK/ERK 1,2 signaling pathways, and hyperproliferation of VSMC. It may be suggested that C-ANP 4-23 could be used as a therapeutic agent in the treatment of vascular remodeling associated with hypertension and atherosclerosis.
Antimicrobial Activity of Pantothenol against Staphylococci Possessing a Prokaryotic Type II Pantothenate Kinase

PubMed Central

Chohnan, Shigeru; Murase, Misa; Kurikawa, Kota; Higashi, Kodai; Ogata, Yuta

2014-01-01

Pantothenol is a provitamin of pantothenic acid (vitamin B5) that is widely used in healthcare and cosmetic products. This analog of pantothenate has been shown to markedly inhibit the phosphorylation activity of the prokaryotic type II pantothenate kinase of Staphylococcus aureus, which catalyzes the first step of the coenzyme A biosynthetic pathway. Since type II enzymes are found exclusively in staphylococci, pantothenol suppresses the growth of S. aureus, S. epidermidis, and S. saprophyticus, which inhabit the skin of humans. Therefore, the addition of this provitamin to ointment and skincare products may be highly effective in preventing infections by opportunistic pathogens. PMID:24759689
Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACE) activity in patients with sarcoidosis.

PubMed

Takemoto, Y; Sakatani, M; Takami, S; Tachibana, T; Higaki, J; Ogihara, T; Miki, T; Katsuya, T; Tsuchiyama, T; Yoshida, A; Yu, H; Tanio, Y; Ueda, E

1998-06-01

Serum angiotensin converting enzyme (SACE) is considered to reflect disease activity in sarcoidosis. SACE activity is increased in many patients with active sarcoid lesions. The mechanism for the increased SACE activity in this disease has not been clarified. ACE insertion/deletion (I/D) gene polymorphism has been reported to have an association with SACE levels in sarcoidosis, but no evidence of an association between angiotensin II receptor gene polymorphism and SACE in this disease has been found. A study of the association of angiotensin II receptor gene polymorphisms with sarcoidosis was therefore undertaken. ACE (I/D), angiotensin II type 1 receptor (AGTR1), and angiotensin II type 2 receptor (AGTR2) gene polymorphisms were investigated by polymerase chain reaction (PCR) and SACE levels were measured in three groups of patients: those with sarcoidosis or tuberculosis and normal controls. There was no difference in allele frequency of AGTR1 and AGTR2 polymorphism among the three groups. Neither AGTR1 nor AGTR2 polymorphisms were associated with sarcoidosis. SACE activity was higher in patients with sarcoidosis with the AGTR1 A/C genotype than in others. However, this tendency was not detected in patients with tuberculosis. The AGTR1 allele C is associated with high activity of SACE in patients with sarcoidosis. It is another predisposing factor for high levels of SACE in patients with sarcoidosis and is considered to be an independent factor from the ACE D allele for high levels of SACE in sarcoidosis. This fact could be one of the explanations for the increased SACE activity in sarcoidosis.
Binding and activation of major histocompatibility complex class II-deficient macrophages by staphylococcal exotoxins

NASA Technical Reports Server (NTRS)

Beharka, A. A.; Armstrong, J. W.; Iandolo, J. J.; Chapes, S. K.; Spooner, B. S. (Principal Investigator)

1994-01-01

Macrophages from C2D transgenic mice deficient in the expression of major histocompatibility complex (MHC) class II proteins were used to identify binding sites for superantigens distinct from the MHC class II molecule. Iodinated staphylococcal enterotoxins A and B (SEA and SEB) and exfoliative toxins A and B (ETA and ETB) bound to C2D macrophages in a concentration-dependent and competitive manner. All four toxins increased F-actin concentration within 30 s of their addition to C2D macrophages, indicating that signal transduction occurred in response to toxin in the absence of class II MHC. Furthermore, ETA, ETB, SEA, and, to a lesser extent, SEB induced C2D macrophages to produce interleukin 6. Several molecular species on C2D macrophages with molecular masses of 140, 97, 61, 52, 43, and 37 kDa bound SEA in immunoprecipitation experiments. These data indicate the presence of novel, functionally active toxin binding sites on murine macrophages distinct from MHC class II molecules.
ANALYSIS OF OPTICAL Fe II EMISSION IN A SAMPLE OF ACTIVE GALACTIC NUCLEUS SPECTRA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kovacevic, Jelena; Popovic, Luka C.; Dimitrijevic, Milan S., E-mail: jkovacevic@aob.bg.ac.r

We present a study of optical Fe II emission in 302 active galactic nuclei (AGNs) selected from the Sloan Digital Sky Survey. We group the strongest Fe II multiplets into three groups according to the lower term of the transition (b{sup 4} F, a{sup 6} S, and a{sup 4} G terms). These approximately correspond to the blue, central, and red parts, respectively, of the 'iron shelf' around H{beta}. We calculate an Fe II template that takes into account transitions into these three terms and an additional group of lines, based on a reconstruction of the spectrum of I Zw 1.more » This Fe II template gives a more precise fit of the Fe II lines in broad-line AGNs than other templates. We extract Fe II, H{alpha}, H{beta}, [O III], and [N II] emission parameters and investigate correlations between them. We find that Fe II lines probably originate in an intermediate line region. We note that the blue, red, and central parts of the iron shelf have different relative intensities in different objects. Their ratios depend on continuum luminosity, FWHM H{beta}, the velocity shift of Fe II, and the H{alpha}/H{beta} flux ratio. We examine the dependence of the well-known anti-correlation between the equivalent widths of Fe II and [O III] on continuum luminosity. We find that there is a Baldwin effect for [O III] but an inverse Baldwin effect for the Fe II emission. The [O III]/Fe II ratio thus decreases with L {sub {lambda}5100}. Since the ratio is a major component of the Boroson and Green Eigenvector 1 (EV1), this implies a connection between the Baldwin effect and EV1 and could be connected with AGN evolution. We find that spectra are different for H{beta} FWHMs greater and less than {approx}3000 km s{sup -1}, and that there are different correlation coefficients between the parameters.« less
KEY COMPARISON: BIPM comparison BIPM.RI(II)-K1.Cu-64 of the activity measurements of the radionuclide 64Cu

NASA Astrophysics Data System (ADS)

Michotte, C.; Courte, S.; Ratel, G.; Kossert, K.; Nähle, O. J.

2009-01-01

In 2009, the Physikalisch-Technische Bundesanstalt (PTB), Germany, submitted a sample of known activity of 64Cu to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM). The value of the activity submitted was about 9.3 MBq. The result of this new comparison has been approved for publication by Section II of the Consultative Committee for Ionizing Radiation (CCRI(II)), comparison identifier BIPM.RI(II)-K1.Cu-64. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI Section II, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).
Anticancer activity of botanical alkyl hydroquinones attributed to topoisomerase II poisoning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, C.-P.; Fang, W.-H.; Lin, L.-I.

2008-03-15

Cytotoxic alkyl hydroquinone compounds have been isolated from many plants. We previously isolated 3 structurally similar cytotoxic alkyl hydroquinone compounds from the sap of the lacquer tree Rhus succedanea L. belonging to the sumac family, which have a long history of medicinal use in Asia. Each has an unsaturated alkyl chain attached to the 2-position of a hydroquinone ring. One of these isolates, 10'(Z),13'(E),15'(E)-heptadecatrienylhydroquinone [HQ17(3)], being the most cytotoxic, was chosen for studying the anticancer mechanism of these compounds. We found that HQ17(3) was a topoisomerase (Topo) II poison. It irreversibly inhibited Topo II{alpha} activity through the accumulation of Topomore » II-DNA cleavable complexes. A cell-based assay showed that HQ17(3) inhibited the growth of leukemia HL-60 cells with an EC{sub 50} of 0.9 {mu}M, inhibited the topoisomerase-II-deficient cells HL-60/MX2 with an EC{sub 50} of 9.6 {mu}M, and exerted no effect on peripheral blood mononuclear cells at concentrations up to 50 {mu}M. These results suggest that Topo II is the cellular drug target. In HL-60 cells, HQ17(3) promptly inhibited DNA synthesis, induced chromosomal breakage, and led to cell death with an EC{sub 50} about one-tenth that of hydroquinone. Pretreatment of the cells with N-acetylcysteine could not attenuate the cytotoxicity and DNA damage induced by HQ17(3). However, N-acetylcysteine did significantly reduce the cytotoxicity of hydroquinone. In F344 rats, intraperitoneal injection of HQ17(3) for 28 days induced no clinical signs of toxicity. These results indicated that HQ17(3) is a potential anticancer agent, and its structural features could be a model for anticancer drug design.« less
Recovering actives in multi-antitarget and target design of analogs of the myosin II inhibitor blebbistatin

NASA Astrophysics Data System (ADS)

Roman, Bart I.; Guedes, Rita C.; Stevens, Christian V.; García-Sosa, Alfonso T.

2018-05-01

In multitarget drug design, it is critical to identify active and inactive compounds against a variety of targets and antitargets. Multitarget strategies thus test the limits of available technology, be that in screening large databases of compounds versus a large number of targets, or in using in silico methods for understanding and reliably predicting these pharmacological outcomes. In this paper, we have evaluated the potential of several in silico approaches to predict the target, antitarget and physicochemical profile of (S)-blebbistatin, the best-known myosin II ATPase inhibitor, and a series of analogs thereof. Standard and augmented structure-based design techniques could not recover the observed activity profiles. A ligand-based method using molecular fingerprints was, however, able to select actives for myosin II inhibition. Using further ligand- and structure-based methods, we also evaluated toxicity through androgen receptor binding, affinity for an array of antitargets and the ADME profile (including assay-interfering compounds) of the series. In conclusion, in the search for (S)-blebbistatin analogs, the dissimilarity distance of molecular fingerprints to known actives and the computed antitarget and physicochemical profile of the molecules can be used for compound design for molecules with potential as tools for modulating myosin II and motility-related diseases.
Structural characterization and antioxidant properties of Cu(II) and Ni(II) complexes derived from dicyandiamide

NASA Astrophysics Data System (ADS)

Kertmen, Seda Nur; Gonul, Ilyas; Kose, Muhammet

2018-01-01

New Cu(II) and Ni(II) complexes derived from dicyandiamide were synthesized and characterised by spectroscopic and analytical methods. Molecular structures of the complexes were determined by single crystal X-ray diffraction studies. In the complexes, the Cu(II) or Ni(II) ions are four-coordinate with a slight distorted square planar geometry. The ligands (L-nPen and L-iPen) derived from dicyandiamide formed via nucleophilic addition of alcohol solvent molecule in the presence Cu(II) or Ni(II) ions. Complexes were stabilised by intricate array of hydrogen bonding interactions. Antioxidant activity of the complexes was evaluated by DPPH radical scavenging and CUPRAC methods. The complexes exhibit antioxidant activity, however, their activities were much lower than standard antioxidants (Vitamin C and trolox).
Ability of the new AT1 receptor blocker azilsartan to block angiotensin II-induced AT1 receptor activation after wash-out.

PubMed

Miura, Shin-ichiro; Matsuo, Yoshino; Nakayama, Asuka; Tomita, Sayo; Suematsu, Yasunori; Saku, Keijiro

2014-03-01

The recently approved angiotensin II (Ang II) type 1 (AT1) receptor blocker (ARB) azilsartan strongly reduces blood pressure (BP) in patients with hypertension. We previously reported that azilsartan showed unique binding behavior to the AT1 receptor because of its 5-oxo-1,2,4-oxadiazole moiety. However, the ability of azilsartan to block Ang II-dependent AT1 receptor activation is not yet clear. Azilsartan and a derivative of azilsartan (azilsartan-7H) that lacks a carboxyl group at the benzimidazole ring were used. Ang II-induced inositol phosphate (IP) production and extracellular signal-regulated kinase (ERK) activation were analyzed in a cell-based wash-out assay. Azilsartan, but not azilsartan-7H, completely blocked Ang II-induced IP production and ERK activation. Our previous report demonstrated that azilsartan mainly interacts with Tyr(113), Lys(199), and Gln(257) in the AT1 receptor. The interactions between azilsartan and Tyr(113) and Gln(257), but not Lys(199), were critical for blocking Ang II-induced IP production and ERK activation after wash-out. Although our findings regarding the molecule-specific effects of azilsartan are based on basic research, they may lead to an exciting insight into the mechanism of azilsartan.
p53 activation by Ni(II) is a HIF-1α independent response causing caspases 9/3-mediated apoptosis in human lung cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, Victor C.; Morse, Jessica L.; Zhitkovich, Anatoly, E-mail: anatoly_zhitkovich@brown.edu

2013-06-15

Hypoxia mimic nickel(II) is a human respiratory carcinogen with a suspected epigenetic mode of action. We examined whether Ni(II) elicits a toxicologically significant activation of the tumor suppressor p53, which is typically associated with genotoxic responses. We found that treatments of H460 human lung epithelial cells with NiCl{sub 2} caused activating phosphorylation at p53-Ser15, accumulation of p53 protein and depletion of its inhibitor MDM4 (HDMX). Confirming the activation of p53, its knockdown suppressed the ability of Ni(II) to upregulate MDM2 and p21 (CDKN1A). Unlike DNA damage, induction of GADD45A by Ni(II) was p53-independent. Ni(II) also increased p53-Ser15 phosphorylation and p21more » expression in normal human lung fibroblasts. Although Ni(II)-induced stabilization of HIF-1α occurred earlier, it had no effect on p53 accumulation and Ser15 phosphorylation. Ni(II)-treated H460 cells showed no evidence of necrosis and their apoptosis and clonogenic death were suppressed by p53 knockdown. The apoptotic role of p53 involved a transcription-dependent program triggering the initiator caspase 9 and its downstream executioner caspase 3. Two most prominently upregulated proapoptotic genes by Ni(II) were PUMA and NOXA but only PUMA induction required p53. Knockdown of p53 also led to derepression of antiapoptotic MCL1 in Ni(II)-treated cells. Overall, our results indicate that p53 plays a major role in apoptotic death of human lung cells by Ni(II). Chronic exposure to Ni(II) may promote selection of resistant cells with inactivated p53, providing an explanation for the origin of p53 mutations by this epigenetic carcinogen. - Highlights: • Ni(II) is a strong activator of the transcription factor p53. • Apoptosis is a principal form of death by Ni(II) in human lung epithelial cells. • Ni(II)-activated p53 triggers caspases 9/3-mediated apoptotic program. • NOXA and PUMA are two main proapoptotic genes induced by Ni(II). • HIF-1α and p53 are
Central sympathoexcitatory actions of angiotensin II: role of type 1 angiotensin II receptors.

PubMed

DiBona, G F

1999-01-01

The role of the renin-angiotensin system in the control of sympathetic nerve activity is reviewed. Two general mechanisms are considered, one that involves the effects of circulating angiotensin II (AngII) on the central nervous system and a second that involves the central nervous system effects of AngII that originates within the central nervous system. The role of type 1 AngII receptors in discrete brain sites that mediate the sympathoexcitatory actions of AngII of either circulating or central nervous system origin is examined. AngII of circulating origin has ready access to the subfornical organ and area postrema, where it can bind to type 1 AngII receptors on neurons whose connections to the nucleus tractus solitarius and rostral ventrolateral medulla result in sympathoexcitation. In the rostral ventrolateral medulla, angiotensin peptides of central nervous system origin, likely involving angiotensin species in addition to AngII and binding to receptors other than type 1 or 2 AngII receptors, tonically support sympathetic nerve activity.
Brain-Mediated Dysregulation of the Bone Marrow Activity in Angiotensin II-induced Hypertension

PubMed Central

Jun, Joo Yun; Zubcevic, Jasenka; Qi, Yanfei; Afzal, Aqeela; Carvajal, Jessica Marulanda; Thinschmidt, Jeffrey S; Grant, Maria B.; Mocco, J; Raizada, Mohan K

2012-01-01

Oxidative stress in the brain is implicated in increased sympathetic drive, inflammatory status and vascular dysfunctions, associated with development and establishment of hypertension. However, little is known about the mechanism of this impaired brain-vascular communication. Here, we tested the hypothesis that increased oxidative stress in the brain cardioregulatory areas, such as the paraventricular nucleus (PVN) of the hypothalamus, is driven by mitochondrial reactive oxygen species (ROS) and leads to increased inflammatory cells (ICs) and decreased/dysfunctional endothelial progenitor cells (EPCs), thereby compromising vasculature repair and accelerating hypertension. Chronic angiotensin II (Ang II) infusion resulted in elevated blood pressure and sympathetic vasomotor drive, decreased spontaneous baroreflex gain, and increased microglia activation in the PVN. This was associated with 46% decrease in BM EPCs and 250% increase in BM ICs, resulting in 5 fold decrease of EPCs/ICs ratio in the BM. Treatment with mitoTEMPO, a scavenger of mitochondrial O2−• intracerebroventricularly but not subcutaneously, attenuated Ang II-induced hypertension, decreased activation of microglia in the PVN, and normalized EPCs/ICs. This functional communication between the brain and BM was confirmed by retrograde neuronal labeling from the BM with GFP-tagged pseudorabies virus (PRV). Administration of GFP-PRV into the BM resulted in predominant labeling of PVN neurons within 3 days, with some fluorescence in the NTS, RVLM and SFO. Taken together, these data demonstrate that inhibition of mitochondrial ROS attenuates Ang II-induced hypertension and corrects the imbalance in EPCs/ICs in the BM. They suggest that an imbalance in vascular reparative and ICs may perpetuate vascular pathophysiology in this model of hypertension. PMID:23045460
Innovative combination of electrolysis and Fe(II)-activated persulfate oxidation for improving the dewaterability of waste activated sludge.

PubMed

Zhen, Guang-Yin; Lu, Xue-Qin; Li, Yu-You; Zhao, You-Cai

2013-05-01

The feasibility of electrolysis integrated with Fe(II)-activated persulfate (S2O8(2-)) oxidation to improve waste activated sludge (WAS) dewaterability was evaluated. The physicochemical properties (sludge volume (SV), total suspended solids (TSS) and volatile suspended solids (VSS)) and extracellular polymeric substances (EPS), including slime EPS, loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS) were characterized to identify their exact roles in sludge dewatering. While dewaterability negatively corresponded to LB-EPS, TB-EPS, protein (PN) and polysaccharide (PS) in LB-EPS and TB-EPS, it was independent of SV, TSS, VSS, slime EPS and PN/PS. Further study through scanning electron microscope (SEM) verified the entrapment of bacterial cells by TB-EPS, protecting them against electrolysis disruption. Comparatively, electrolysis integrated with S2O8(2-)/Fe(II) oxidation was able to effectively disrupt the protective barrier and crack the entrapped cells, releasing the water inside EPS and cells. Therefore, the destruction of both TB-EPS and cells is the fundamental reason for the enhanced dewaterability. Copyright © 2013 Elsevier Ltd. All rights reserved.
Anti-proliferative activities on HeLa cancer cell line of Thai medicinal plant recipes selected from MANOSROI II database.

PubMed

Manosroi, Jiradej; Boonpisuttinant, Korawinwich; Manosroi, Worapaka; Manosroi, Aranya

2012-07-13

The Thai/Lanna medicinal plant recipe database "MANOSROI II" contained the medicinal plant recipes of all regions in Thailand for the treatment of various diseases including anti-cancer medicinal plant recipes. To investigate anti-proliferative activity on HeLa cell lines of medicinal plant recipes selected from the Thai/Lanna medicinal plant recipe database "MANOSROI II". The forty aqueous extracts of Thai/Lanna medicinal plant recipes selected from the Thai/Lanna medicinal plant recipe database "MANOSROI II" were investigated for anti-proliferative activity on HeLa cell line by SRB assay. The apoptosis induction by caspase-3 activity and MMP-2 inhibition activity by zymography on HeLa cell line of the three selected aqueous extracts, which gave the highest anti-proliferative activity were determined. Phytochemicals and anti-oxidative activities including free radical scavenging activity, inhibition of lipid peroxidation and metal chelating inhibition activities were also investigated. Sixty percentages of the medicinal plant recipes selected from "MANOSROI II" database showed anti-proliferative activity on HeLa cell line. The recipes of N031(Albizia chinensis (Osbeck) Merr, Cassia fistula L., and Dargea volubilis Benth.ex Hook. etc.), N039 (Nymphoides indica L., Peltophorum pterocarpum (DC.), and Polyalthia debilis Finet et Gagnep etc.) and N040 (Nymphoides indica L. Kuntze, Sida rhombifolia L., and Xylinbaria minutiflora Pierre. etc.) gave higher anti-proliferative activity than the standard anti-cancer drug, cisplatin of 1.25, 1.29 and 30.18 times, respectively. The positive relationship between the anti-proliferative activity and the MMP-2 inhibition activity and metal chelating inhibition activity was observed, but no relationship between the anti-proliferative activity and apoptosis induction, free radical scavenging activity and lipid peroxidation inhibition activity. Phytochemicals found in these extracts were alkaloids, flavonoids, tannins and xanthones
Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACE) activity in patients with sarcoidosis

PubMed Central

Takemoto, Y.; Sakatani, M.; Takami, S.; Tachibana, T.; Higaki, J.; Ogihara, T.; Miki, T.; Katsuya, T.; Tsuchiyama, T.; Yoshida, A.; Yu, H.; Tanio, Y.; Ueda, E.

1998-01-01

BACKGROUND—Serum angiotensin converting enzyme (SACE) is considered to reflect disease activity in sarcoidosis. SACE activity is increased in many patients with active sarcoid lesions. The mechanism for the increased SACE activity in this disease has not been clarified. ACE insertion/deletion (I/D) gene polymorphism has been reported to have an association with SACE levels in sarcoidosis, but no evidence of an association between angiotensin II receptor gene polymorphism and SACE in this disease has been found. A study of the association of angiotensin II receptor gene polymorphisms with sarcoidosis was therefore undertaken. METHODS—ACE (I/D), angiotensin II type 1 receptor (AGTR1), and angiotensin II type 2 receptor (AGTR2 ) gene polymorphisms were investigated by polymerase chain reaction (PCR) and SACE levels were measured in three groups of patients: those with sarcoidosis or tuberculosis and normal controls. RESULTS—There was no difference in allele frequency of AGTR1 and AGTR2 polymorphism among the three groups. Neither AGTR1 nor AGTR2 polymorphisms were associated with sarcoidosis. SACE activity was higher in patients with sarcoidosis with the AGTR1 A/C genotype than in others. However, this tendency was not detected in patients with tuberculosis. CONCLUSIONS—The AGTR1 allele C is associated with high activity of SACE in patients with sarcoidosis. It is another predisposing factor for high levels of SACE in patients with sarcoidosis and is considered to be an independent factor from the ACE D allele for high levels of SACE in sarcoidosis. This fact could be one of the explanations for the increased SACE activity in sarcoidosis.   PMID:9713444

Redesigning the blue copper azurin into a redox-active mononuclear nonheme iron protein: preparation and study of Fe(II)-M121E azurin.

PubMed

Liu, Jing; Meier, Katlyn K; Tian, Shiliang; Zhang, Jun-Long; Guo, Hongchao; Schulz, Charles E; Robinson, Howard; Nilges, Mark J; Münck, Eckard; Lu, Yi

2014-09-03

Much progress has been made in designing heme and dinuclear nonheme iron enzymes. In contrast, engineering mononuclear nonheme iron enzymes is lagging, even though these enzymes belong to a large class that catalyzes quite diverse reactions. Herein we report spectroscopic and X-ray crystallographic studies of Fe(II)-M121E azurin (Az), by replacing the axial Met121 and Cu(II) in wild-type azurin (wtAz) with Glu and Fe(II), respectively. In contrast to the redox inactive Fe(II)-wtAz, the Fe(II)-M121EAz mutant can be readily oxidized by Na2IrCl6, and interestingly, the protein exhibits superoxide scavenging activity. Mössbauer and EPR spectroscopies, along with X-ray structural comparisons, revealed similarities and differences between Fe(II)-M121EAz, Fe(II)-wtAz, and superoxide reductase (SOR) and allowed design of the second generation mutant, Fe(II)-M121EM44KAz, that exhibits increased superoxide scavenging activity by 2 orders of magnitude. This finding demonstrates the importance of noncovalent secondary coordination sphere interactions in fine-tuning enzymatic activity.
Synthesis and biological activities of new furo[3,4-b]carbazoles: potential topoisomerase II inhibitors.

PubMed

Hajbi, Youssef; Neagoie, Cléopatra; Biannic, Bérenger; Chilloux, Aurélie; Vedrenne, Emeline; Baldeyrou, Brigitte; Bailly, Christian; Mérour, Jean-Yves; Rosca, Sorin; Routier, Sylvain; Lansiaux, Amélie

2010-11-01

New 1,5-dihydro-4-(substituted phenyl)-3H-furo[3,4-b]carbazol-3-ones were synthesised via a key step Diels-Alder reaction under microwave irradiation. 3-Formylindole was successfully used in a 6-step synthesis to obtain those complex heterocycles. The Diels-Alder reaction generating the carbazole ring was optimised under thermal conditions or microwave irradiation. After cleavage of functional groups, DNA binding, topoisomerase inhibition and cytotoxic properties of the new-formed furocarbazoles were investigated. These carbazoles do not present a strong interaction with the DNA, and do not modify the relaxation of the DNA in the presence of topoisomerase I or II except for one promising compound. This compound is a potent topoisomerase II inhibitor, and its cellular activity is not moderated compared to etoposide. The synthesis of these molecules allowed the generalisation of the method using indole and 5-OBn indole and several benzaldehydes. The synthesis of these molecules produced chemical structures endowed with promising cytotoxic and topoisomerase II inhibition activities. Copyright © 2010 Elsevier Masson SAS. All rights reserved.
C1QTNF1 attenuates angiotensin II-induced cardiac hypertrophy via activation of the AMPKa pathway.

PubMed

Wu, Leiming; Gao, Lu; Zhang, Dianhong; Yao, Rui; Huang, Zhen; Du, Binbin; Wang, Zheng; Xiao, Lili; Li, Pengcheng; Li, Yapeng; Liang, Cui; Zhang, Yanzhou

2018-06-01

Complement C1q tumor necrosis factor related proteins (C1QTNFs) have been reported to have diverse biological influence on the cardiovascular system. C1QTNF1 is a member of the CTRP superfamily. C1QTNF1 is expressed in the myocardium; however, its function in myocytes has not yet been investigated. To systematically investigate the roles of C1QTNF1 in angiotensin II (Ang II)-induced cardiac hypertrophy. C1QTNF1 knock-out mice were used with the aim of determining the role of C1QTNF1 in cardiac hypertrophy in the adult heart. Data from experiments showed that C1QTNF1 was up-regulated during cardiac hypertrophic processes, which were triggered by increased reactive oxygen species. C1QTNF1 deficiency accelerated cardiac hypertrophy, fibrosis, inflammation responses, and oxidative stress with deteriorating cardiac dysfunction in the Ang II-induced cardiac hypertrophy mouse model. We identified C1QTNF1 as a negative regulator of cardiomyocyte hypertrophy in Ang II-stimulated neonatal rat cardiomyocytes using the recombinant human globular domain of C1QTNF1 and C1QTNF1 siRNA. Injection of the recombinant human globular domain of C1QTNF1 also suppressed the Ang II-induced cardiac hypertrophic response in vivo. The anti-hypertrophic effects of C1QTNF1 rely on AMPKa activation, which inhibits mTOR P70S6K phosphorylation. An AMPKa inhibitor abrogated the anti-hypertrophic effects of the recombinant human globular domain of C1QTNF1 both in vivo and vitro. Moreover, C1QTNF1-mediated AMPKa activation was triggered by the inhibition of PDE1-4, which subsequently activated the cAMP/PKA/LKB1 pathway. Our results demonstrated that C1QTNF1 improves cardiac function and inhibits cardiac hypertrophy and fibrosis by increasing and activating AMPKa, suggesting that C1QTNF1 could be a therapeutic target for cardiac hypertrophy and heart failure. Copyright © 2018 Elsevier Inc. All rights reserved.
Discovery of orally active hepatoselective glucokinase activators for treatment of Type II Diabetes Mellitus.

PubMed

Xu, Jiayi; Lin, Songnian; Myers, Robert W; Trujillo, Maria E; Pachanski, Michele J; Malkani, Sunita; Chen, Hsuan-Shen; Chen, Zhesheng; Campbell, Brian; Eiermann, George J; Elowe, Nadine; Farrer, Brian T; Feng, Wen; Fu, Qinghong; Kats-Kagan, Roman; Kavana, Michael; McMasters, Daniel R; Mitra, Kaushik; Tong, Xinchun; Xu, Libo; Zhang, Fengqi; Zhang, Rui; Addona, George H; Berger, Joel P; Zhang, Bei; Parmee, Emma R

2017-05-01

Systemically acting glucokinase activators (GKA) have been demonstrated in clinical trials to effectively lower blood glucose in patients with type II diabetes. However, mechanism-based hypoglycemia is a major adverse effect that limits the therapeutic potential of these agents. We hypothesized that the predominant mechanism leading to hypoglycemia is GKA-induced excessive insulin secretion from pancreatic β-cells at (sub-)euglycemic levels. We further hypothesized that restricting GK activation to hepatocytes would maintain glucose-lowering efficacy while significantly reducing hypoglycemic risk. Here we report the discovery of a novel series of carboxylic acid substituted GKAs based on pyridine-2-carboxamide. These GKAs exhibit preferential distribution to the liver versus the pancreas in mice. SAR studies led to the identification of a potent and orally active hepatoselective GKA, compound 6. GKA 6 demonstrated robust glucose lowering efficacy in high fat diet-fed mice at doses ⩾10mpk, with ⩾70-fold liver:pancreas distribution, minimal effects on plasma insulin levels, and significantly reduced risk of hypoglycemia. Copyright © 2016. Published by Elsevier Ltd.
Vitamin D Receptor Activation Reduces Angiotensin-II-Induced Dissecting Abdominal Aortic Aneurysm in Apolipoprotein E-Knockout Mice.

PubMed

Martorell, Sara; Hueso, Luisa; Gonzalez-Navarro, Herminia; Collado, Aida; Sanz, Maria-Jesus; Piqueras, Laura

2016-08-01

Abdominal aortic aneurysm (AAA) is a vascular disorder characterized by chronic inflammation of the aortic wall. Low concentrations of vitamin D3 are associated with AAA development; however, the potential direct effect of vitamin D3 on AAA remains unknown. This study evaluates the effect of oral treatment with the vitamin D3 receptor (VDR) ligand, calcitriol, on dissecting AAA induced by angiotensin-II (Ang-II) infusion in apoE(-/-) mice. Oral treatment with calcitriol reduced Ang-II-induced dissecting AAA formation in apoE(-/-) mice, which was unrelated to systolic blood pressure or plasma cholesterol concentrations. Immunohistochemistry and reverse-transcription polymerase chain reaction analysis demonstrated a significant increase in macrophage infiltration, neovessel formation, matrix metalloproteinase-2 and matrix metalloproteinase-9, chemokine (CCL2 [(C-C motif) ligand 2], CCL5 [(C-C motif) ligand 5], and CXCL1 [(C-X-C motif) ligand 1]) and vascular endothelial growth factor expression in suprarenal aortic walls of apoE(-/-) mice infused with Ang-II, and all were significantly reduced by cotreatment with calcitriol. Phosphorylation of extracellular signal-regulated kinases 1/2, p38 mitogen-activated protein kinase, and nuclear factor-κB was also decreased in the suprarenal aortas of apoE(-/-) mice cotreated with calcitriol. These effects were accompanied by a marked increase in VDR-retinoid X receptor (RXR) interaction in the aortas of calcitriol-treated mice. In vitro, VDR activation by calcitriol in human endothelial cells inhibited Ang-II-induced leukocyte-endothelial cell interactions, morphogenesis, and production of endothelial proinflammatory and angiogenic chemokines through VDR-RXR interactions, and knockdown of VDR or RXR abolished the inhibitory effects of calcitriol. VDR activation reduces dissecting AAA formation induced by Ang-II in apoE(-/-) mice and may constitute a novel therapeutic strategy to prevent AAA progression. © 2016 American
Fabrication and characterization of mesoporous activated carbon from Lemna minor using one-step H3PO4 activation for Pb(II) removal

NASA Astrophysics Data System (ADS)

Huang, Yang; Li, Shunxing; Lin, Haibin; Chen, Jianhua

2014-10-01

A low cost and locally available material, Lemna minor, was used to fabricate activated carbon using H3PO4 activation. After H3PO4 activation, the L. minor activated carbons (LACs) possess high mesoporosity (92.2%) and a surface area of 531.9 m2/g according to Brunauer-Emmett-Teller (BET) analysis. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectrometer (XPS) analyses reveal the presence of rich hydroxyl, carboxyl, amide and phosphate functional groups on the LACs surface, leading to facile Pb(II) binding to the surface through strong chemisorptive bonds or ion-exchange. The kinetic and equilibrium data were well described by pseudo-first-order model and Langmuir isotherm, with the maximum monolayer adsorption capacity (qm) 170.9 mg/g at 25 °C. The intra-particle diffusion mechanism was partially responsible for the adsorption. The adsorption process was spontaneous and endothermic with negative ΔG and positive ΔH. The Pb(II)-loaded LACs could be easily regenerated using 0.1-M HCl and reused for seven cycles without significant adsorption capacity reduction. The maximum percentage removal rate for Pb(II) (20 mg/L) was found to be 91.8% within 30 min, at optimum conditions of pH 6.0 and 25 °C. These suggested that the low-cost LACs could be used as a potential adsorbent in the treatment of lead-contaminated water.
Removal of Cd(II) from aqueous solution with activated Firmiana Simplex Leaf: behaviors and affecting factors.

PubMed

Tang, Qiang; Tang, Xiaowu; Hu, Manman; Li, Zhenze; Chen, Yunmin; Lou, Peng

2010-07-15

Cadmium pollution is known to cause severe public health problems. This study is intended to examine the effect of an activated Firmiana Simplex Leaf (FSL) on the removal of Cd(II) from aqueous solution. Results showed that the active Firmiana Simplex Leaf could efficiently remove Cd(II) from wastewater due to the preservation of beneficial groups (amine, carboxyl, and phosphate) at a temperature of 250 degrees C. The adsorbent component, dosage, concentration of the initial solute, and the pH of the solution were all found to have significant effects on Cd(II) adsorption. The kinetic constants were predicted by pseudo-first-order kinetics, and the thermodynamic analysis revealed the endothermic and spontaneous nature of the adsorption. FT-IR and XRD analyses confirmed the strong adsorption between beneficial groups and cadmium ions, and the adsorption capacity was calculated to be 117.786 mg g(-1) according to the Langmuir isotherm. 2010 Elsevier B.V. All rights reserved.
Activity of pyramidal I and II < c + a > slip in Mg alloys as revealed by texture development

NASA Astrophysics Data System (ADS)

Zecevic, Miroslav; Beyerlein, Irene J.; Knezevic, Marko

2018-02-01

Due to the geometry of the hexagonal close-packed (HCP) lattice, there are two types of pyramidal slip modes: { 10 1 bar 1 } 〈 11 2 bar 3 bar 〉 or type I and { 1 bar 1 bar 22 } 〈 11 2 bar 3 〉 or type II in HCP crystalline materials. Here we use crystal plasticity to examine the importance of crystallographic slip by pyramidal type I and type II on texture evolution. The study is applied to an Mg-4%Li alloy. An elastic-plastic polycrystal model is employed to elucidate the reorientation tendencies of these two slip modes in rolling of a textured polycrystal. Comparisons with experimental texture measurements indicate that both pyramidal I and II type slip were active during rolling deformation, with pyramidal I being the dominant mode. A single-slip-mode analysis is used to identify the orientations that prefer pyramidal I vs. II type slip when acting alone in a crystal. The analysis applies not only to Mg-4%Li, but identifies the key texture components in HCP crystals that would help distinguish the activity of pyramidal I from pyramidal II slip in rolling deformation.
Structural and Biological Behaviour of Co(II), Cu(II) and Ni(II) Metal Complexes of Some Amino Acid Derived Schiff-Bases

PubMed Central

Chohan, Zahid H.; Praveen, M.; Ghaffar, A.

1997-01-01

Biologically active tridentate amino acid (Alanine, Glycine & Tyrosine) derived Schiff-bases and their Co(II), Cu(II) & Ni(II) complexes have been synthesised and characterised on the basis of their conductance and magnetic measurements, elemental analysis and 13C-NMR, 1H-NMR, IR and electronic spectral data. These Schiff-bases and their complexes have been evaluated for their antibacterial activity against bacterial species such as Staphylococcus aureus, Escherichia coli, Klebsiella pneumonae, Proteus vulgarus and Pseudomonas aeruginosa and this activity data show the metal complexes to be more antibacterial than the Schiff-bases against one or more bacterial species. PMID:18475798
The role of the peripheral benzodiazepine receptor in photodynamic activity of certain pyropheophorbide ether photosensitizers: albumin site II as a surrogate marker for activity.

PubMed

Dougherty, Thomas J; Sumlin, Adam B; Greco, William R; Weishaupt, Kenneth R; Vaughan, Lurine A; Pandey, Ravindra K

2002-07-01

A study has been carried out to define the importance of the peripheral benzodiazepine receptor (PBR) as a binding site for a series of chlorin-type photosensitizers, pyropheophorbide-a ethers, the subject of a previous quantitative structure-activity relationship study by us. The effects of the PBR ligand PK11195 on the photodynamic activity have been determined in vivo for certain members of this series of alkyl-substituted ethers: two of the most active derivatives (hexyl and heptyl), the least active derivative (dodecyl [C12]) and one of intermediate activity (octyl [C8]). The photodynamic therapy (PDT) effect was inhibited by PK11195 for both of the most active derivatives, but no effect on PDT activity was found for the less active C12 or C8 ethers. The inhibitory effects of PK11195 were predicted by the binding of only the active derivatives to the benzodiazepine site on albumin, ie. human serum albumin (HSA)-Site II. Thus, as with certain other types of photosensitizers, it has been demonstrated with this series of pyropheophorbide ethers that in vitro binding to HSA-Site II is a predictor of both optimal in vivo activity and binding to the PBR in vivo.
5-Nitroimidazole-derived Schiff bases and their copper(II) complexes exhibit potent antimicrobial activity against pathogenic anaerobic bacteria.

PubMed

Oliveira, Alexandre A; Oliveira, Ana P A; Franco, Lucas L; Ferencs, Micael O; Ferreira, João F G; Bachi, Sofia M P S; Speziali, Nivaldo L; Farias, Luiz M; Magalhães, Paula P; Beraldo, Heloisa

2018-05-07

In the present work a family of novel secnidazole-derived Schiff base compounds and their copper(II) complexes were synthesized. The antimicrobial activities of the compounds were evaluated against clinically important anaerobic bacterial strains. The compounds exhibited in vitro antibacterial activity against Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovatus, Parabacteroides distasonis and Fusubacterium nucleatum pathogenic anaerobic bacteria. Upon coordination to copper(II) the antibacterial activity significantly increased in several cases. Some derivatives were even more active than the antimicrobial drugs secnidazole and metronidazole. Therefore, the compounds under study are suitable for in vivo evaluation and the microorganisms should be classified as susceptible to them. Electrochemical studies on the reduction of the nitro group revealed that the compounds show comparable reduction potentials, which are in the same range of the bio-reducible drugs secnidazole and benznidazole. The nitro group reduction potential is more favorable for the copper(II) complexes than for the starting ligands. Hence, the antimicrobial activities of the compounds under study might in part be related to intracellular bio-reduction activation. Considering the increasing resistance rates of anaerobic bacteria against a wide range of antimicrobial drugs, the present work constitutes an important contribution to the development of new antibacterial drug candidates.
The Star Formation Reference Survey - II. Activity demographics and host-galaxy properties for infrared-selected galaxies

NASA Astrophysics Data System (ADS)

Maragkoudakis, A.; Zezas, A.; Ashby, M. L. N.; Willner, S. P.

2018-04-01

We present activity demographics and host-galaxy properties of infrared-selected galaxies in the local Universe, using the representative Star Formation Reference Survey (SFRS). Our classification scheme is based on a combination of optical emission-line diagrams (BPT) and infrared (IR)-colour diagnostics. Using the weights assigned to the SFRS galaxies based on its parent sample, a far-IR-selected sample comprises 71 per cent H II galaxies, 13 per cent Seyferts, 3 per cent transition objects (TOs), and 13 per cent low-ionization nuclear emission-line regions (LINERs). For the SFRS H II galaxies, we derive nuclear star formation rates and gas-phase metallicities. We measure host-galaxy metallicities for all galaxies with available long-slit spectroscopy and abundance gradients for a subset of 12 face-on galaxies. The majority of H II galaxies show a narrow range of metallicities, close to solar, and flat metallicity profiles. Based on their host-galaxy and nuclear properties, the dominant ionizing source in the far-infrared selected TOs is star-forming activity. LINERs are found mostly in massive hosts (median of 1010.5 M⊙), median L(60 μm) = 109 L⊙, median dust temperatures of F60/F100 = 0.36, and median LH α surface density of 1040.2 erg s-1kpc-2, indicating older stellar populations as their main ionizing source rather than active galactic nucleus activity.
Study of anti-fibrillogenic activity of iron(II) clathrochelates.

PubMed

Kovalska, Vladyslava B; Losytskyy, Mykhaylo Yu; Varzatskii, Oleg A; Cherepanov, Vsevolod V; Voloshin, Yan Z; Mokhir, Andriy A; Yarmoluk, Sergiy M; Volkov, Sergiy V

2014-03-15

The macrocyclic compounds mono- and bis-iron(II) clathrochelates were firstly studied as potential anti-fibrillogenic agents using fluorescent inhibitory assay, atomic force microscopy and flow cytometry. It is shown that presence of the clathrochelates leads to the change in kinetics of insulin fibrillization reaction and reduces the amount of formed fibrils (up to 70%). The nature of ribbed substituent could determine the activity of clathrochelates-the higher inhibitory effect is observed for compounds containing carboxybenzenesulfide groups, while the inhibitory properties only slightly depend on the size of complex species. The mono- and bis-clathrochelate derivatives of meta-mercaptobenzoic acid have close values of IC₅₀ namely 16 ± 2 and 24 ± 5 μM, respectively. The presence of clathrochelates decreases the fibril diameter from 5-12 nm for free insulin fibrils to 3-8 nm for these formed in the clathrochelate presence, it also prevents the lateral aggregation of mature fibrils and formation of superfibrillar clusters. However the addition of clathrochelate results in more heterogeneous (both by size and structure) insulin aggregates population as compared to the free insulin. This way, cage complexes-iron(II) clathrochelates are proposed as efficient agents able to suppress the protein aggregation processes. Copyright © 2014 Elsevier Ltd. All rights reserved.
THE Fe II EMISSION IN ACTIVE GALACTIC NUCLEI: EXCITATION MECHANISMS AND LOCATION OF THE EMITTING REGION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marinello, M.; Rodríguez-Ardila, A.; Garcia-Rissmann, A.

2016-04-01

We present a study of Fe ii emission in the near-infrared region (NIR) for 25 active galactic nuclei (AGNs) to obtain information about the excitation mechanisms that power it and the location where it is formed. We employ an NIR Fe ii template derived in the literature and find that it successfully reproduces the observed Fe ii spectrum. The Fe ii bump at 9200 Å detected in all objects studied confirms that Lyα fluorescence is always present in AGNs. The correlation found between the flux of the 9200 Å bump, the 1 μm lines, and the optical Fe ii implies that Lyα fluorescencemore » plays an important role in Fe ii production. We determined that at least 18% of the optical Fe ii is due to this process, while collisional excitation dominates the production of the observed Fe ii. The line profiles of Fe ii λ10502, O i λ11287, Ca ii λ8664, and Paβ were compared to gather information about the most likely location where they are emitted. We found that Fe ii, O i and Ca ii have similar widths and are, on average, 30% narrower than Paβ. Assuming that the clouds emitting the lines are virialized, we show that the Fe ii is emitted in a region twice as far from the central source than Paβ. The distance, though, strongly varies: from 8.5 light-days for NGC 4051 to 198.2 light-days for Mrk 509. Our results reinforce the importance of the Fe ii in the NIR to constrain critical parameters that drive its physics and the underlying AGN kinematics, as well as more accurate models aimed at reproducing this complex emission.« less
Angiotensin II regulates brain (pro)renin receptor expression through activation of cAMP response element-binding protein

PubMed Central

Li, Wencheng; Liu, Jiao; Hammond, Sean L.; Tjalkens, Ronald B.; Saifudeen, Zubaida

2015-01-01

We reported that brain (pro)renin receptor (PRR) expression levels are elevated in DOCA-salt-induced hypertension; however, the underlying mechanism remained unknown. To address whether ANG II type 1 receptor (AT1R) signaling is involved in this regulation, we implanted a DOCA pellet and supplied 0.9% saline as the drinking solution to C57BL/6J mice. Sham pellet-implanted mice that were provided regular drinking water served as controls. Concurrently, mice were intracerebroventricularly infused with the AT1R blocker losartan, angiotensin-converting-enzyme inhibitor captopril, or artificial cerebrospinal fluid for 3 wk. Intracerebroventricular infusion of losartan or captopril attenuated DOCA-salt-induced PRR mRNA elevation in the paraventricular nucleus of the hypothalamus, suggesting a role for ANG II/AT1R signaling in regulating PRR expression during DOCA-salt hypertension. To test which ANG II/AT1R downstream transcription factors were involved in PRR regulation, we treated Neuro-2A cells with ANG II with or without CREB (cAMP response element-binding protein) or AP-1 (activator protein-1) inhibitors, or CREB siRNA. CREB and AP-1 inhibitors, as well as CREB knockdown abolished ANG II-induced increases in PRR levels. ANG II also induced PRR upregulation in primary cultured neurons. Chromatin immunoprecipitation assays revealed that ANG II treatment increased CREB binding to the endogenous PRR promoter in both cultured neurons and hypothalamic tissues of DOCA-salt hypertensive mice. This increase in CREB activity was reversed by AT1R blockade. Collectively, these findings indicate that ANG II acts via AT1R to upregulate PRR expression both in cultured cells and in DOCA-salt hypertensive mice by increasing CREB binding to the PRR promoter. PMID:25994957
Relationships Between RNA Polymerase II Activity and Spt Elongation Factors to Spt- Phenotype and Growth in Saccharomyces cerevisiae

PubMed Central

Cui, Ping; Jin, Huiyan; Vutukuru, Manjula Ramya; Kaplan, Craig D.

2016-01-01

The interplay between adjacent transcription units can result in transcription-dependent alterations in chromatin structure or recruitment of factors that determine transcription outcomes, including the generation of intragenic or other cryptic transcripts derived from cryptic promoters. Mutations in a number of genes in Saccharomyces cerevisiae confer both cryptic intragenic transcription and the Suppressor of Ty (Spt-) phenotype for the lys2-128∂ allele of the LYS2 gene. Mutants that suppress lys2-128∂ allow transcription from a normally inactive Ty1 ∂ promoter, conferring a LYS+ phenotype. The arrangement of transcription units at lys2-128∂ is reminiscent of genes containing cryptic promoters within their open reading frames. We set out to examine the relationship between RNA Polymerase II (Pol II) activity, functions of Spt elongation factors, and cryptic transcription because of the previous observation that increased-activity Pol II alleles confer an Spt- phenotype. We identify both cooperating and antagonistic genetic interactions between Pol II alleles and alleles of elongation factors SPT4, SPT5, and SPT6. We find that cryptic transcription at FLO8 and STE11 is distinct from that at lys2-128∂, though all show sensitivity to reduction in Pol II activity, especially the expression of lys2-128∂ found in Spt- mutants. We determine that the lys2-128∂ Spt- phenotypes for spt6-1004 and increased activity rpo21/rpb1 alleles each require transcription from the LYS2 promoter. Furthermore, we identify the Ty1 transcription start site (TSS) within the ∂ element as the position of Spt- transcription in tested Spt- mutants. PMID:27261007
Preparation, characterisation and study of in vitro biologically active azamacrocyclic Cu(II) dicarboxylate complexes

NASA Astrophysics Data System (ADS)

Antonijević-Nikolić, Mirjana; Antić-Stanković, Jelena; Tanasković, Sladjana B.; Korabik, Maria J.; Gojgić-Cvijović, Gordana; Vučković, Gordana

2013-12-01

New cationic Cu(II) complexes with N, N‧, N″, N″‧-tetrakis(2-pyridylmethyl)-1,4,8,11-tetraazacyclotetradecane (tpmc) and aliphatic dicarboxylic acids: pentanedioic (glutaric acid = glutH2), hexanedioic acid (adipic acid = adipH2) and decanedioic acid (sebacic acid = sebH2) of general formula [Cu4(L)(tpmc)2](ClO4)6·xH2O, L = glut, x = 2; L = adip, x = 7; L = seb, x = 6 were isolated. Their composition and charges are proposed based on elemental analyses and molar conductivity measurements. By the comparison of their UV-Vis, reflectance, FTIR and EPR spectral data, CV and SQUID magnetic measurements, with those for the complex with butanedioic acid (succinic acid = succH2) of known molecular structure and analysis of LC/MS spectra, geometry with two [Cu2tpmc]4+ units bridged by dicarboxylate dianion engaging all oxygens is proposed. Within units, Cu(II) ions are also bridged with N portion of cyclam ring. All four complexes were screened to in vitro antimicrobial and cytotoxic activity along with free primary and secondary ligands, Cu(II) salt and solvent controls. Detected antibacterial and cytotoxic activity for the complexes was enhanced in most cases than the corresponding controls.
Anti-proliferative and apoptosis induction activities of extracts from Thai medicinal plant recipes selected from MANOSROI II database.

PubMed

Manosroi, Jiradej; Sainakham, Mathukorn; Manosroi, Worapaka; Manosroi, Aranya

2012-05-07

ETHONOPHARMACOLOGICAL RELEVANCES: Traditional medicines have long been used by the Thai people. Several medicinal recipes prepared from a mixture of plants are often used by traditional medicinal practitioners for the treatment of many diseases including cancer. The recipes collected from the Thai medicinal text books were recorded in MANOSROI II database. Anticancer recipes were searched and selected by a computer program using the recipe indication keywords including Ma-reng and San which means cancer in Thai, from the database for anticancer activity investigation. To investigate anti-cancer activities of the Thai medicinal plant recipes selected from the "MANOSROI II" database. Anti-proliferative and apoptotic activities of extracts from 121 recipes selected from 56,137 recipes in the Thai medicinal plant recipe "MANOSROI II" database were investigated in two cancer cell lines including human mouth epidermal carcinoma (KB) and human colon adenocarcinoma (HT-29) cell lines using sulforhodamine B (SRB) assay and acridine orange (AO) and ethidium bromide (EB) staining technique, respectively. In the SRB assay, recipes NE028 and, S003 gave the highest anti-proliferation activity on KB and HT29 with the IC(50) values of 2.48±0.24 and 6.92±0.49μg/ml, respectively. In the AO/EB staining assay, recipes S016 and NE028 exhibited the highest apoptotic induction in KB and HT-29 cell lines, respectively. This study has demonstrated that the three Thai medicinal plant recipes selected from "MANOSROI II" database (NE028, S003 and S016) gave active anti-cancer activities according to the NCI classification which can be further developed for anti-cancer treatment. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
From Synthesis to Biological Impact of Pd (II) Complexes: Synthesis, Characterization, and Antimicrobial and Scavenging Activity

PubMed Central

Sharma, Nitin Kumar; Ameta, Rakesh Kumar; Singh, Man

2016-01-01

The Pd (II) complexes with a series of halosubstituted benzylamine ligands (BLs) have been synthesized and characterized with different spectroscopic technique such as FTIR, UV/Vis, LCMS, 1H, and 13C NMR. Their molecular sustainability in different solvents such as DMSO, DMSO : H2O, and DMSO : PBS at physiological condition (pH 7.2) was determined by UV/Vis spectrophotometer. The in vitro antibacterial and antifungal activities of the complexes were investigated against Gram-positive and Gram-negative microbes and two different fungi indicated their significant biological potential. Additionally, their antioxidant activity has been analyzed with DPPH• free radical through spectrophotometric method and the result inferred them as an antioxidant. The stronger antibacterial and antioxidant activities of the synthesized complexes suggested them as a stronger antimicrobial agent. Our study advances the biological importance of palladium (II) amine complexes in the field of antimicrobial and antioxidant activities. PMID:27119023
Designing of Protein Kinase C β-II Inhibitors against Diabetic complications: Structure Based Drug Design, Induced Fit docking and analysis of active site conformational changes

PubMed Central

Vijayakumar, Balakrishnan; Velmurugan, Devadasan

2012-01-01

Protein Kinase C β-II (PKC β-II) is an important enzyme in the development of diabetic complications like cardiomyopathy, retinopathy, neuropathy, nephropathy and angiopathy. PKC β-II is activated in vascular tissues during diabetic vascular abnormalities. Thus, PKC β-II is considered as a potent drug target and the crystal structure of the kinase domain of PKC β-II (PDB id: 2I0E) was used to design inhibitors using Structure-Based Drug Design (SBDD) approach. Sixty inhibitors structurally similar to Staurosporine were retrieved from PubChem Compound database and High Throughput Virtual screening (HTVs) was carried out with PKC β-II. Based on the HTVs results and the nature of active site residues of PKC β-II, Staurosporine inhibitors were designed using SBDD. Induced Fit Docking (IFD) studies were carried out between kinase domain of PKC β-II and the designed inhibitors. These IFD complexes showed favorable docking score, glide energy, glide emodel and hydrogen bond and hydrophobic interactions with the active site of PKC β-II. Binding free energy was calculated for IFD complexes using Prime MM-GBSA method. The conformational changes induced by the inhibitor at the active site of PKC β-II were observed for the back bone Cα atoms and side-chain chi angles. PASS prediction tool was used to analyze the biological activities for the designed inhibitors. The various physicochemical properties were calculated for the compounds. One of the designed inhibitors successively satisfied all the in silico parameters among the others and seems to be a potent inhibitor against PKC β-II. PMID:22829732

miR-34a Modulates Angiotensin II-Induced Myocardial Hypertrophy by Direct Inhibition of ATG9A Expression and Autophagic Activity

PubMed Central

Huang, He; Ye, Jing; Pan, Wei; Zhong, Yun; Cheng, Chuanfang; You, Xiangyu; Liu, Benrong; Xiong, Longgen; Liu, Shiming

2014-01-01

Cardiac hypertrophy is characterized by thickening myocardium and decreasing in heart chamber volume in response to mechanical or pathological stress, but the underlying molecular mechanisms remain to be defined. This study investigated altered miRNA expression and autophagic activity in pathogenesis of cardiac hypertrophy. A rat model of myocardial hypertrophy was used and confirmed by heart morphology, induction of cardiomyocyte autophagy, altered expression of autophagy-related ATG9A, LC3 II/I and p62 proteins, and decrease in miR-34a expression. The in vitro data showed that in hypertrophic cardiomyocytes induced by Ang II, miR-34a expression was downregulated, whereas ATG9A expression was up-regulated. Moreover, miR-34a was able to bind to ATG9A 3′-UTR, but not to the mutated 3′-UTR and inhibited ATG9A protein expression and autophagic activity. The latter was evaluated by autophagy-related LC3 II/I and p62 levels, TEM, and flow cytometry in rat cardiomyocytes. In addition, ATG9A expression induced either by treatment of rat cardiomyocytes with Ang II or ATG9A cDNA transfection upregulated autophagic activity and cardiomyocyte hypertrophy in both morphology and expression of hypertrophy-related genes (i.e., ANP and β-MHC), whereas knockdown of ATG9A expression downregulated autophagic activity and cardiomyocyte hypertrophy. However, miR-34a antagonized Ang II-stimulated myocardial hypertrophy, whereas inhibition of miR-34a expression aggravated Ang II-stimulated myocardial hypertrophy (such as cardiomyocyte hypertrophy-related ANP and β-MHC expression and cardiomyocyte morphology). This study indicates that miR-34a plays a role in regulation of Ang II-induced cardiomyocyte hypertrophy by inhibition of ATG9A expression and autophagic activity. PMID:24728149
Synthesis and studies on Cu(II), Co(II), Ni(II) complexes of Knoevenagel β-diketone ligands.

PubMed

Sumathi, S; Tharmaraj, P; Sheela, C D; Anitha, C

2012-11-01

Transition metal complexes of various acetylacetone based ligands of the type ML [where M=Cu(II), Ni(II), Co(II); L=3-(aryl)-pentane-2,4-dione] have been synthesized. The structural features have been derived from their elemental analysis, magnetic susceptibility, molar conductance, IR, UV-Vis, (1)H NMR, Mass and ESR spectral studies. Conductivity measurements reveal that all the complexes are non-electrolytic in nature. Spectroscopic and other analytical data of the complexes suggest octahedral geometry for other metal(II) complexes. The redox behavior of the copper(II) complexes have been studied by cyclic voltammetry. The free ligands and their metal complexes have been screened for their in vitro biological activities against the bacteria Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus as well as the fungus Candida albicans by well diffusion method. The zone of inhibition value indicates that the most of the metal(II) complexes are found to possess increased activities compared to those of the free ligands. All synthesized compounds may serve as potential photoactive materials as indicated from their characteristic fluorescence properties. The second harmonic generation (SHG) efficiency of the ligands (L1-L3) was found to be considerable effect than that of urea and KDP (potassium dihydrogen phosphate). Copyright © 2012 Elsevier B.V. All rights reserved.
Synthesis and studies on Cu(II), Co(II), Ni(II) complexes of Knoevenagel β-diketone ligands

NASA Astrophysics Data System (ADS)

Sumathi, S.; Tharmaraj, P.; Sheela, C. D.; Anitha, C.

2012-11-01

Transition metal complexes of various acetylacetone based ligands of the type ML [where M = Cu(II), Ni(II), Co(II); L = 3-(aryl)-pentane-2,4-dione] have been synthesized. The structural features have been derived from their elemental analysis, magnetic susceptibility, molar conductance, IR, UV-Vis, 1H NMR, Mass and ESR spectral studies. Conductivity measurements reveal that all the complexes are non-electrolytic in nature. Spectroscopic and other analytical data of the complexes suggest octahedral geometry for other metal(II) complexes. The redox behavior of the copper(II) complexes have been studied by cyclic voltammetry. The free ligands and their metal complexes have been screened for their in vitro biological activities against the bacteria Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus as well as the fungus Candida albicans by well diffusion method. The zone of inhibition value indicates that the most of the metal(II) complexes are found to possess increased activities compared to those of the free ligands. All synthesized compounds may serve as potential photoactive materials as indicated from their characteristic fluorescence properties. The second harmonic generation (SHG) efficiency of the ligands (L1-L3) was found to be considerable effect than that of urea and KDP (potassium dihydrogen phosphate).
Repression of enhancer II activity by a negative regulatory element in the hepatitis B virus genome.

PubMed Central

Lo, W Y; Ting, L P

1994-01-01

Enhancer II of human hepatitis B virus has dual functions in vivo. Located at nucleotides (nt) 1646 to 1741, it can stimulate the surface and X promoters from a downstream position. Moreover, the same sequence can also function as upstream regulatory element that activates the core promoter in a position- and orientation-dependent manner. In this study, we report the identification and characterization of a negative regulatory element (NRE) upstream of enhancer II (nt 1613 to 1636) which can repress both the enhancer and upstream stimulatory function of the enhancer II sequence in differentiated liver cells. This NRE has marginal inhibitory effect by itself but a strong repressive function in the presence of a functional enhancer II. Mutational analysis reveals that sequence from nt 1616 to 1621 is required for repression of enhancer activity by the NRE. Gel shift analysis reveals that this negative regulatory region can be recognized by a specific protein factor(s) present at the 0.4 M NaCl fraction of HepG2 nuclear extracts. The discovery of the NRE indicates that HBV gene transcription is controlled by combined effects of both positive and negative regulation. It also provides a unique system with which to study the mechanism of negative regulation of gene expression. Images PMID:8107237
ANO1 contributes to angiotensin-II-activated Ca2+-dependent Cl- current in human atrial fibroblasts.

PubMed

El Chemaly, Antoun; Norez, Caroline; Magaud, Christophe; Bescond, Jocelyn; Chatelier, Aurelien; Fares, Nassim; Findlay, Ian; Jayle, Christophe; Becq, Frederic; Faivre, Jean-François; Bois, Patrick

2014-03-01

Cardiac fibroblasts are an integral part of the myocardial tissue and contribute to its remodelling. This study characterises for the first time the calcium-dependent chloride channels (CaCC) in the plasma membrane of primary human atrial cardiac fibroblasts by means of the iodide efflux and the patch clamp methods. The calcium ionophore A23187 and Angiotensin II (Ang II) activate a chloride conductance in cardiac fibroblasts that shares pharmacological similarities with calcium-dependent chloride channels. This chloride conductance is depressed by RNAi-mediated selective Anoctamine 1 (ANO1) but not by Anoctamine 2 (ANO2) which has been revealed as CaCC and is inhibited by the selective ANO1 inhibitor, T16inh-A01. The effect of Ang II on anion efflux is mediated through AT1 receptors (with an EC50 = 13.8 ± 1.3 nM). The decrease of anion efflux by calphostin C and bisindolylmaleimide I (BIM I) suggests that chloride conductance activation is dependent on PKC. We conclude that ANO1 contributes to CaCC current in human cardiac fibroblasts and that this is regulated by Ang II acting via the AT1 receptor pathway. Copyright © 2014 Elsevier Ltd. All rights reserved.
Isotherm and thermodynamic studies of Zn (II) adsorption on lignite and coconut shell-based activated carbon fiber.

PubMed

Shrestha, Sohan; Son, Guntae; Lee, Seung Hwan; Lee, Tae Gwan

2013-08-01

The Zn (II) adsorption capacity of lignite and coconut shell-based activated carbon fiber (ACF) was evaluated as a function of initial Zn (II) concentration, temperature and contact time in batch adsorption process in this study. Adsorption uptake increased with initial Zn (II) concentration and temperature. Optimal contact time for the adsorption of Zn (II) ions onto lignite and coconut shell-based ACF was found to be 50 min. Removal percentage decreased from 88.0% to 78.54% with the increment in initial Zn (II) concentration from 5 to 50 mg L(-1). Equilibrium data fit well with Langmuir-I isotherm indicating homogeneous monolayer coverage of Zn (II) ions on the adsorbent surface. Maximum monolayer adsorption capacity of Zn (II) ions on ACF was found to be 9.43 mg g(-1). Surface morphology and functionality of ACF prior to and after adsorption were characterized by electron microscopy and infrared spectroscopy. Various thermodynamic parameters such as standard Gibbs free energy (ΔG°), standard enthalpy (ΔH°), and standard entropy (ΔS°) were evaluated. Copyright © 2013 Elsevier Ltd. All rights reserved.
IGF-II-mediated downregulation of peroxisome proliferator-activated receptor-γ coactivator-1α in myoblast cells involves PI3K/Akt/FoxO1 signaling pathway.

PubMed

Mu, Xiaoyu; Qi, Weihong; Liu, Yunzhang; Zhou, Jianfeng; Li, Yun; Rong, Xiaozhi; Lu, Ling

2017-08-01

Insulin-like growth factor II (IGF-II) can stimulate myogenesis and is critically involved in skeletal muscle differentiation. The presence of negative regulators of this process, however, is not well explored. Here, we showed that in myoblast cells, IGF-II negatively regulated peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mRNA expression, while constitutive expression of PGC-1α induced myoblast differentiation. These results suggest that the negative regulation of PGC-1α by IGF-II may act as a negative feedback mechanism in IGF-II-induced myogenic differentiation. Reporter assays demonstrated that IGF-II suppresses the basal PGC-1α promoter activity. Blocking the IGF-II signaling pathway increased the endogenous PGC-1α levels. In addition, pharmacological inhibition of PI3 kinase activity prevented the downregulation of PGC-1α but the activation of mTOR was not required for this process. Importantly, further analysis showed that forkhead transcription factor FoxO1 contributes to mediating the effects of IGF-II on PGC-1 promoter activity. These findings indicate that IGF-II reduces PGC-1α expression in skeletal muscle cells through a mechanism involving PI3K-Akt-FoxO1 but not p38 MAPK or Erk1/2 MAPK pathways.
Active site nanospace of aminoacyl tRNA synthetase: difference between the class I and class II synthetases.

PubMed

Dutta, Saheb; Choudhury, Kaberi; Banik, Sindrila Dutta; Nandi, Nilashis

2014-03-01

The present work is aimed at understanding the origin of the difference in the molecular organization of the active site nanospaces of the class I and class II aminoacyl tRNA synthetases (aaRSs) which are tunnel-like structures. The active site encloses the cognate amino acid (AA) and the adenosine triphosphate (ATP) to carry out aminoacylation reaction. Comparison of the structures of the active site of the class I and class II (aaRSs) shows that the nanodimensional tunnels are curved in opposite directions in the two classes. We investigated the origin of this difference using quantum mechanical computation of electrostatic potential (ESP) of substrates, surrounding residues and ions, using Atoms in Molecule (AIM) Theory and charge population analysis. We show that the difference is principally due to the variation in the spatial charge distribution of ATP in the two classes which correspond to extended and bent conformations of ATP. The present computation shows that the most feasible pathway for nucleophilic attack to alphaP is oppositely directed for class I and class II aaRSs. The available crystal structures show that the cognate AA is indeed located along the channel favorable for nucleophilic attack as predicted by the ESP analysis. It is also shown that the direction of the channel changes its orientation when the orientation of ATP is changed from extended to a bent like structure. We further used the AIM theory to confirm the direction of the approach of AA in each case and the results corroborate the results from the ESP analysis. The opposite curvatures of the active site nanospaces in class I and class II aaRSs are related with the influence of the charge distributions of the extended and bent conformations of ATP, respectively. The results of the computation of electrostatic potential by successive addition of active site residues show that their roles on the reaction are similar in both classes despite the difference in the organization of the
Angiotensin II AT1 receptor alters ACE2 activity, eNOS expression and CD44-hyaluronan interaction in rats with hypertension and myocardial fibrosis.

PubMed

Bai, Feng; Pang, Xue-Fen; Zhang, Li-Hui; Wang, Ning-Ping; McKallip, Robert J; Garner, Ronald E; Zhao, Zhi-Qing

2016-05-15

This study tested the hypothesis that angiotensin II (Ang II) AT1 receptor is involved in development of hypertension and cardiac fibrosis via modifying ACE2 activity, eNOS expression and CD44-hyaluronan interaction. Male Sprague-Dawley rats were subjected to Ang II infusion (500ng/kg/min) using osmotic minipumps up to 4weeks and the AT1 receptor blocker, telmisartan was administered by gastric gavage (10mg/kg/day) during Ang II infusion. Our results indicated that Ang II enhances AT1 receptor, downregulates AT2 receptor, ACE2 activity and eNOS expression, and increases CD44 expression and hyaluronidase activity, an enzyme for hyaluronan degradation. Further analyses revealed that Ang II increases blood pressure and augments vascular/interstitial fibrosis. Comparison of the Ang II group, treatment with telmisartan significantly increased ACE2 activity and eNOS expression in the intracardiac vessels and intermyocardium. These changes occurred in coincidence with decreased blood pressure. Furthermore, the locally-expressed AT1 receptor was downregulated, as evidenced by an increased ratio of the AT2 over AT1 receptor (1.4±0.4% vs. 0.4±0.1% in Ang II group, P<0.05). Along with these modulations, telmisartan inhibited membrane CD44 expression and hyaluronidase activity, decreased populations of macrophages and myofibroblasts, and reduced expression of TGFβ1 and Smads. Collagen I synthesis and tissue fibrosis were attenuated as demonstrated by the less extensive collagen-rich area. These results suggest that the AT1 receptor is involved in development of hypertension and cardiac fibrosis. Selective activating ACE2/eNOS and inhibiting CD44/HA interaction might be considered as the therapeutic targets for attenuating Ang II induced deleterious cardiovascular effects. Copyright © 2016 Elsevier Inc. All rights reserved.
Synthesis, spectral characterization, structural investigation and antimicrobial studies of mononuclear Cu(II), Ni(II), Co(II), Zn(II) and Cd(II) complexes of a new potentially hexadentate N2O4 Schiff base ligand derived from salicylaldehyde

NASA Astrophysics Data System (ADS)

Keypour, Hassan; Shayesteh, Maryam; Rezaeivala, Majid; Chalabian, Firoozeh; Elerman, Yalcin; Buyukgungor, Orhan

2013-01-01

A new potentially hexadentate N2O4 Schiff base ligand, H2L derived from condensation reaction of an aromatic diamine and salicylaldehyde, and its metal complexes were characterized by elemental analyses, IR, UV-Vis, EI-MS, 1H and 13C NMR spectra, as well as conductance measurements. It has been originated that the Schiff base ligand with Cu(II), Ni(II), Co(II), Cd(II) and Zn(II) ions form mononuclear complexes on 1:1 (metal:ligand) stoichiometry. The conductivity data confirm the non-electrolytic nature of the complexes. Also the crystal structures of the complexes [ZnL] and [CoL] have also been determined by using X-ray crystallographic technique. The Zn(II) and Co(II) complexes show a tetrahedral configuration. Electronic absorption spectra of the Cu(II) and Ni(II) complexes suggest a square-planar geometry around the central metal ion. The synthesized compounds have antibacterial activity against the three Gram-positive bacteria: Bacillus cereus, Enterococcus faecalis and Listeria monocytogenes and also against the three Gram-negative bacteria: Salmonella paraB, Citrobacter freundii and Enterobacter aerogenes. The results showed that in some cases the antibacterial activity of complexes were more than nalidixic acid and amoxicillin as standards.
DSIF and RNA polymerase II CTD phosphorylation coordinate the recruitment of Rpd3S to actively transcribed genes.

PubMed

Drouin, Simon; Laramée, Louise; Jacques, Pierre-Étienne; Forest, Audrey; Bergeron, Maxime; Robert, François

2010-10-28

Histone deacetylase Rpd3 is part of two distinct complexes: the large (Rpd3L) and small (Rpd3S) complexes. While Rpd3L targets specific promoters for gene repression, Rpd3S is recruited to ORFs to deacetylate histones in the wake of RNA polymerase II, to prevent cryptic initiation within genes. Methylation of histone H3 at lysine 36 by the Set2 methyltransferase is thought to mediate the recruitment of Rpd3S. Here, we confirm by ChIP-Chip that Rpd3S binds active ORFs. Surprisingly, however, Rpd3S is not recruited to all active genes, and its recruitment is Set2-independent. However, Rpd3S complexes recruited in the absence of H3K36 methylation appear to be inactive. Finally, we present evidence implicating the yeast DSIF complex (Spt4/5) and RNA polymerase II phosphorylation by Kin28 and Ctk1 in the recruitment of Rpd3S to active genes. Taken together, our data support a model where Set2-dependent histone H3 methylation is required for the activation of Rpd3S following its recruitment to the RNA polymerase II C-terminal domain.
Effect of pre-exposure of human erythrocytes to oxidants on the haemolytic activity of Sticholysin II. A comparison between peroxynitrite and hypochlorous acid.

PubMed

Celedón, Gloria; González, Gustavo; Lissi, Eduardo; Cerda, Tania; Bascuñant, Denisse; Lepeley, Marcia; Pazos, Fabiola; Lanio, Maria E; Alvarez, Carlos

2011-04-01

Stichodactyla heliantus II (St II) is a haemolytic toxin whose activity depends of the characteristics of red blood cells (RBC). Among the factors that may tune the response of the RBC to the toxin activity stand the oxidative status of the cell. This study investigates how pre-oxidation of RBC modifies St II activity employing two oxidants, peroxynitrite and hypochlorous acid. Results show that peroxynitrite-treated RBC are more resistant to St II activity. On the other hand, hypochlorous acid-treated RBC become more susceptible to St II. This contrasting behaviour of both oxidants is related to the modifications elicited in RBC by both oxidant agents. Peroxynitrite does not modify RBC osmotic fragility but reduces anion transport through band 3 protein. This effect, together with an increase in K+ efflux, can explain the increased resistance to the toxin activity. On the other hand, results obtained with hypochlorous acid can be explained in terms of a disruption of the membrane organization without the compensating effect of a reduction in band 3-mediated anion transport. The present results, obtained employing the effect of a model haemolytic toxin on RBC, emphasize the specificity of the RBC response to different endogenous oxidative agents.
Signaling, Regulation, and Specificity of the Type II p21-activated Kinases.

PubMed

Ha, Byung Hak; Morse, Elizabeth M; Turk, Benjamin E; Boggon, Titus J

2015-05-22

The p21-activated kinases (PAKs) are a family of six serine/threonine kinases that act as key effectors of RHO family GTPases in mammalian cells. PAKs are subdivided into two groups: type I PAKs (PAK1, PAK2, and PAK3) and type II PAKs (PAK4, PAK5, and PAK6). Although these groups are involved in common signaling pathways, recent work indicates that the two groups have distinct modes of regulation and have both unique and common substrates. Here, we review recent insights into the molecular level details that govern regulation of type II PAK signaling. We also consider mechanisms by which signal transduction is regulated at the level of substrate specificity. Finally, we discuss the implications of these studies for clinical targeting of these kinases. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
Synthesis and application of surface-imprinted activated carbon sorbent for solid-phase extraction and determination of copper (II)

NASA Astrophysics Data System (ADS)

Li, Zhenhua; Li, Jingwen; Wang, Yanbin; Wei, Yajun

2014-01-01

A new Cu(II)-imprinted amino-functionalized activated carbon sorbent was prepared by a surface imprinting technique for selective solid-phase extraction (SPE) of Cu(II) prior to its determination by inductively coupled plasma atomic emission spectrometry (ICP-AES). Experimental conditions for effective adsorption of Cu(II) were optimized with respect to different experimental parameters using static and dynamic procedures in detail. Compared with non-imprinted sorbent, the ion-imprinted sorbent had higher selectivity and adsorption capacity for Cu(II). The maximum static adsorption capacity of the ion-imprinted and non-imprinted sorbent for Cu(II) was 26.71 and 6.86 mg g-1, respectively. The relatively selectivity factor values (αr) of Cu(II)/Zn(II), Cu(II)/Ni(II), Cu(II)/Co(II) and Cu(II)/Pb(II) were 166.16, 50.77, 72.26 and 175.77, respectively, which were greater than 1. Complete elution of the adsorbed Cu(II) from Cu(II)-imprinted sorbent was carried out using 2 mL of 0.1 mol L-1 EDTA solution. The relative standard deviation of the method was 2.4% for eleven replicate determinations. The method was validated for the analysis by two certified reference materials (GBW 08301, GBW 08303), the results obtained is in good agreement with standard values. The developed method was also successfully applied to the determination of trace copper in natural water samples with satisfactory results.
Synthesis and application of surface-imprinted activated carbon sorbent for solid-phase extraction and determination of copper (II).

PubMed

Li, Zhenhua; Li, Jingwen; Wang, Yanbin; Wei, Yajun

2014-01-03

A new Cu(II)-imprinted amino-functionalized activated carbon sorbent was prepared by a surface imprinting technique for selective solid-phase extraction (SPE) of Cu(II) prior to its determination by inductively coupled plasma atomic emission spectrometry (ICP-AES). Experimental conditions for effective adsorption of Cu(II) were optimized with respect to different experimental parameters using static and dynamic procedures in detail. Compared with non-imprinted sorbent, the ion-imprinted sorbent had higher selectivity and adsorption capacity for Cu(II). The maximum static adsorption capacity of the ion-imprinted and non-imprinted sorbent for Cu(II) was 26.71 and 6.86 mg g(-1), respectively. The relatively selectivity factor values (αr) of Cu(II)/Zn(II), Cu(II)/Ni(II), Cu(II)/Co(II) and Cu(II)/Pb(II) were 166.16, 50.77, 72.26 and 175.77, respectively, which were greater than 1. Complete elution of the adsorbed Cu(II) from Cu(II)-imprinted sorbent was carried out using 2 mL of 0.1 mol L(-1) EDTA solution. The relative standard deviation of the method was 2.4% for eleven replicate determinations. The method was validated for the analysis by two certified reference materials (GBW 08301, GBW 08303), the results obtained is in good agreement with standard values. The developed method was also successfully applied to the determination of trace copper in natural water samples with satisfactory results. Copyright © 2013 Elsevier B.V. All rights reserved.
Toll-Like Receptor 2 Mediates Cellular Activation by the B Subunits of Type II Heat-Labile Enterotoxins

PubMed Central

Hajishengallis, George; Tapping, Richard I.; Martin, Michael H.; Nawar, Hesham; Lyle, Elizabeth A.; Russell, Michael W.; Connell, Terry D.

2005-01-01

The type II heat-labile enterotoxins (LT-IIa and LT-IIb) of Escherichia coli have an AB5 subunit structure similar to that of cholera toxin (CT) and other type I enterotoxins, despite significant differences in the amino acid sequences of their B subunits and different ganglioside receptor specificities. LT-II holotoxins and their nontoxic B subunits display unique properties as immunological adjuvants distinct from those of CT and its B subunits. In contrast to type II holotoxins, the corresponding pentameric B subunits, LT-IIaB and LT-IIbB, stimulated cytokine release in both human and mouse cells dependent upon Toll-like receptor 2 (TLR2). Induction of interleukin-1β (IL-1β), IL-6, IL-8, or tumor necrosis factor alpha in human THP-1 cells by LT-IIaB or LT-IIbB was inhibited by anti-TLR2 but not by anti-TLR4 antibody. Furthermore, transient expression of TLR1 and TLR2 in human embryonic kidney 293 cells resulted in activation of a nuclear factor-κB-dependent luciferase gene in response to LT-IIaB or LT-IIbB. Moreover, peritoneal macrophages from TLR2-deficient mice failed to respond to LT-IIaB or LT-IIbB, in contrast to wild-type or TLR4-deficient cells. These results demonstrate that besides their established binding to gangliosides, the B subunits of type II enterotoxins also interact with TLR2. Although a ganglioside-nonbinding mutant (T34I) of LT-IIaB effectively induced cytokine release, a phenotypically similar point mutation (T13I) in LT-IIbB abrogated cytokine induction, suggesting a variable requirement for gangliosides as coreceptors in TLR2 agonist activity. TLR2-dependent activation of mononuclear cells by type II enterotoxin B subunits appears to be a novel mechanism whereby these molecules may exert their immunomodulatory and adjuvant activities. PMID:15731031
UCS Protein Rng3p Is Essential for Myosin-II Motor Activity during Cytokinesis in Fission Yeast

PubMed Central

Stark, Benjamin C.; James, Michael L.; Pollard, Luther W.; Sirotkin, Vladimir; Lord, Matthew

2013-01-01

UCS proteins have been proposed to operate as co-chaperones that work with Hsp90 in the de novo folding of myosin motors. The fission yeast UCS protein Rng3p is essential for actomyosin ring assembly and cytokinesis. Here we investigated the role of Rng3p in fission yeast myosin-II (Myo2p) motor activity. Myo2p isolated from an arrested rng3-65 mutant was capable of binding actin, yet lacked stability and activity based on its expression levels and inactivity in ATPase and actin filament gliding assays. Myo2p isolated from a myo2-E1 mutant (a mutant hyper-sensitive to perturbation of Rng3p function) showed similar behavior in the same assays and exhibited an altered motor conformation based on limited proteolysis experiments. We propose that Rng3p is not required for the folding of motors per se, but instead works to ensure the activity of intrinsically unstable myosin-II motors. Rng3p is specific to conventional myosin-II and the actomyosin ring, and is not required for unconventional myosin motor function at other actin structures. However, artificial destabilization of myosin-I motors at endocytic actin patches (using a myo1-E1 mutant) led to recruitment of Rng3p to patches. Thus, while Rng3p is specific to myosin-II, UCS proteins are adaptable and can respond to changes in the stability of other myosin motors. PMID:24244528
Spectroscopic characterization, antioxidant and antitumour studies of novel bromo substituted thiosemicarbazone and its copper(II), nickel(II) and palladium(II) complexes

NASA Astrophysics Data System (ADS)

Jagadeesh, M.; Lavanya, M.; Kalangi, Suresh K.; Sarala, Y.; Ramachandraiah, C.; Varada Reddy, A.

2015-01-01

A new, slightly distorted octahedral complex of copper(II), square planar complexes of nickel(II) and palladium(II) with 2,4‧-dibromoacetophenone thiosemicarbazone (DBAPTSC) are synthesized. The ligand and the complexes are characterized by FT-IR, FT-Raman, powder X-ray diffraction studies. The IR and Raman data are correlated for the presence of the functional groups which specifically helped in the confirmation of the compounds. In addition, the free ligand is unambiguously characterized by 1H and 13C NMR spectroscopy while the copper(II) complex is characterized by electron paramagnetic resonance spectroscopy (EPR). The g values for the same are found to be 2.246 (g1), 2.012 (g2) and 2.005 (g3) which suggested rhombic distortions. The HOMO-LUMO band gap calculations for these compounds are found to be in between 0.5 and 4.0 eV and these compounds are identified as semiconducting materials. The synthesized ligand and its copper(II), nickel(II) and palladium(II) complexes are subjected to antitumour activity against the HepG2 human hepatoblastoma cell lines. Among all the compounds, nickel(II) complex is found to exert better antitumour activity with 57.6% of cytotoxicity.
AN ANGIOTENSIN II TYPE 1 RECEPTOR ACTIVATION SWITCH PATCH REVEALED THROUGH EVOLUTIONARY TRACE ANALYSIS

PubMed Central

Bonde, Marie Mi; Yao, Rong; Ma, Jian-Nong; Madabushi, Srinivasan; Haunsø, Stig; Burstein, Ethan S.; Whistler, Jennifer L.; Sheikh, Søren P.; Lichtarge, Olivier; Hansen, Jakob Lerche

2010-01-01

Seven transmembrane (7TM) or G protein-coupled receptors constitute a large superfamily of cell surface receptors sharing a structural motif of seven transmembrane spanning alpha helices. Their activation mechanism most likely involves concerted movements of the transmembrane helices, but remains to be completely resolved. Evolutionary Trace (ET) analysis is a computational method, which identifies clusters of functionally important residues by integrating information on evolutionary important residue variations with receptor structure. Combined with known mutational data, ET predicted a patch of residues in the cytoplasmic parts of TM2, TM3, and TM6 to form an activation switch that is common to all family A 7TM receptors. We tested this hypothesis in the rat Angiotensin II (Ang II) type 1 (AT1) receptor. The receptor has important roles in the cardiovascular system, but has also frequently been applied as a model for 7TM receptor activation and signaling. Six mutations: F66A, L67R, L70R, L119R, D125A, and I245F were targeted to the putative switch and assayed for changes in activation state by their ligand binding, signaling, and trafficking properties. All but one receptor mutant (that was not expressed well) displayed phenotypes associated with changed activation state, such as increased agonist affinity or basal activity, promiscuous activation, or constitutive internalization highlighting the importance of testing different signaling pathways. We conclude that this evolutionary important patch mediates interactions important for maintaining the inactive state. More broadly, these observations in the AT1 receptor are consistent with computational predictions of a generic role for this patch in 7TM receptor activation. PMID:20227396
Zeolite-encapsulated Co(II), Mn(II), Cu(II) and Cr(III) salen complexes as catalysts for efficient selective oxidation of benzyl alcohol

NASA Astrophysics Data System (ADS)

Li, F. H.; Bi, H.; Huang, D. X.; Zhang, M.; Song, Y. B.

2018-01-01

Co(II), Mn(II), Cu(II) and Cr(III) salen type complexes were synthesized in situ in Y zeolite by the reaction of ion-exchanged metal ions with the flexible ligand molecules that had diffused into the cavities. Data of characterization indicates the formation of metal salen complexes in the pores without affecting the zeolite framework structure, the absence of any extraneous species and the geometry of encapsulated complexes. The catalytic activity results show that Cosalcyen Y exhibited higher catalytic activity in the water phase selective oxidation of benzyl alcohol, which could be attributed to their geometry and the steric environment of the metal actives sites.

Solar Type II Radio Bursts and IP Type II Events

NASA Technical Reports Server (NTRS)

Cane, H. V.; Erickson, W. C.

2005-01-01

We have examined radio data from the WAVES experiment on the Wind spacecraft in conjunction with ground-based data in order to investigate the relationship between the shocks responsible for metric type II radio bursts and the shocks in front of coronal mass ejections (CMEs). The bow shocks of fast, large CMEs are strong interplanetary (IP) shocks, and the associated radio emissions often consist of single broad bands starting below approx. 4 MHz; such emissions were previously called IP type II events. In contrast, metric type II bursts are usually narrowbanded and display two harmonically related bands. In addition to displaying complete dynamic spectra for a number of events, we also analyze the 135 WAVES 1 - 14 MHz slow-drift time periods in 2001-2003. We find that most of the periods contain multiple phenomena, which we divide into three groups: metric type II extensions, IP type II events, and blobs and bands. About half of the WAVES listings include probable extensions of metric type II radio bursts, but in more than half of these events, there were also other slow-drift features. In the 3 yr study period, there were 31 IP type II events; these were associated with the very fastest CMEs. The most common form of activity in the WAVES events, blobs and bands in the frequency range between 1 and 8 MHz, fall below an envelope consistent with the early signatures of an IP type II event. However, most of this activity lasts only a few tens of minutes, whereas IP type II events last for many hours. In this study we find many examples in the radio data of two shock-like phenomena with different characteristics that occur simultaneously in the metric and decametric/hectometric bands, and no clear example of a metric type II burst that extends continuously down in frequency to become an IP type II event. The simplest interpretation is that metric type II bursts, unlike IP type II events, are not caused by shocks driven in front of CMEs.
Simultaneous Stripping Detection of Pb(II), Cd(II) and Zn(II) Using a Bimetallic Hg-Bi/Single-Walled Carbon Nanotubes Composite Electrode

PubMed Central

Ouyang, Ruizhuo; Zhu, Zhenqian; Tatum, Clarissa E.; Chambers, James Q.; Xue, Zi-Ling

2011-01-01

A new, sensitive platform for the simultaneous electrochemical assay of Zn(II), Cd(II) and Pb(II) in aqueous solution has been developed. The platform is based on a new bimetallic Hg-Bi/single-walled carbon nanotubes (SWNTs) composite modified glassy carbon electrode (GCE), demonstrating remarkably improved performance for the anodic stripping assay of Zn(II), Cd(II) and Pb(II). The synergistic effect of Hg and Bi as well as the enlarged, activated surface and good electrical conductivity of SWNTs on GCE contribute to the enhanced activity of the proposed electrode. The analytical curves for Zn(II), Cd(II) an Pb(II) cover two linear ranges varying from 0.5 to 11 μg L-1 and 10 to 130 μg L-1 with correlation coefficients higher than 0.992. The limits of detection for Zn(II), Cd(II) are lower than 2 μg L-1 (S/N = 3). For Pb(II), moreover, there is another lower, linear range from 5 to 1100 ng L-1 with a coefficient of 0.987 and a detection limit of 0.12 ng L-1. By using the standard addition method, Zn(II), Cd(II) and Pb(II) ions in river samples were successfully determined. These results suggest that the proposed method can be applied as a simple, efficient alternative for the simultaneous monitoring of heavy metals in water samples. In addition, this method demonstrates the powerful application of carbon nanotubes in electrochemical analysis of heavy metals. PMID:21660117
Chitosan film loaded with silver nanoparticles-sorbent for solid phase extraction of Al(III), Cd(II), Cu(II), Co(II), Fe(III), Ni(II), Pb(II) and Zn(II).

PubMed

Djerahov, Lubomir; Vasileva, Penka; Karadjova, Irina; Kurakalva, Rama Mohan; Aradhi, Keshav Krishna

2016-08-20

The present study describes the ecofriendly method for the preparation of chitosan film loaded with silver nanoparticles (CS-AgNPs) and application of this film as efficient sorbent for separation and enrichment of Al(III), Cd(II), Cu(II), Co(II), Fe(III), Ni(II), Pb(II) and Zn(II). The stable CS-AgNPs colloid was prepared by dispersing the AgNPs sol in chitosan solution at appropriate ratio and further used to obtain a cast film with very good stability under storage and good mechanical strength for easy handling in aqueous medium. The incorporation of AgNPs in the structure of CS film and interaction between the polymer matrix and nanoparticles were confirmed by UV-vis and FTIR spectroscopy. The homogeneously embedded AgNPs (average diameter 29nm, TEM analysis) were clearly observed throughout the film by SEM. The CS-AgNPs nanocomposite film shows high sorption activity toward trace metals under optimized chemical conditions. The results suggest that the CS-AgNPs nanocomposite film can be feasibly used as a novel sorbent material for solid-phase extraction of metal pollutants from surface waters. Copyright © 2016 Elsevier Ltd. All rights reserved.
Pharmacologically significant complexes of Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) of novel Schiff base ligand, (E)-N-(furan-2-yl methylene) quinolin-8-amine: Synthesis, spectral, XRD, SEM, antimicrobial, antioxidant and in vitro cytotoxic studies

NASA Astrophysics Data System (ADS)

Shakir, M.; Hanif, Summaiya; Sherwani, Mohd. Asif; Mohammad, Owais; Al-Resayes, Saud I.

2015-07-01

A novel series of metal complexes of the types, [ML2(H2O)2]Cl2 and [ML2]Cl2 [M = Mn(II), 1; Co(II), 2; Ni(II), 3; Cu(II), 4; and Zn(II), 5] were synthesized by the interaction of ligand, L (E)-N-(furan-2-yl methylene) quinolin-8-amine, derived from the condensation of 2-furaldehyde and 8-aminoquinoline. The synthesized ligand and its metal complexes were characterized on the basis of results obtained from elemental analysis, ESI-MS, XRD, SEM, TGA/DTA, FT-IR, UV-Vis, magnetic moment and 1H and 13C NMR spectroscopic studies. EPR parameters were recorded in case of complex 4. The comparative in-vitro antimicrobial activities against various pathogens with reference to known antibiotics and antioxidant activity against standard control at variable concentrations revealed that the metal complexes show enhanced antimicrobial and free radical scavenging activities in general as compared to free ligand. However, the complexes 1 and 5 have shown best antioxidant activity among all the metal complexes. Furthermore, comparative in-vitro antiproliferative activity on ligand and its metal chelates performed on MDA-MB-231 (breast carcinoma), KCL22 (blood lymphoid carcinoma), HeLa (cervical carcinoma) cell lines and normal cells (PBMC) revealed that metal chelates show moderate to good activity as compared to ligand where as complex 1 seems to be the most promising one possessing a broad spectrum of activity against all the selected cancer cell lines with IC50 < 2.10 μM.
Geraniol modulates tongue and hepatic phase I and phase II conjugation activities and may contribute directly to the chemopreventive activity against experimental oral carcinogenesis.

PubMed

Madankumar, Arumugam; Jayakumar, Subramaniyan; Gokuladhas, Krishnan; Rajan, Balan; Raghunandhakumar, Subramanian; Asokkumar, Selvamani; Devaki, Thiruvengadam

2013-04-05

Xenobiotic metabolizing enzymes are chief determinants in both the susceptibility to mutagenic effect of chemical carcinogens and in the response of tumors to chemotherapy. The present study was aimed to analyze the effect of geraniol administration on the activity of phase I and phase II carcinogen metabolizing enzymes through the nuclear factor erythroid 2-related factor-2 (Nrf2) activation against 4-niroquinoline-1-oxide (4NQO) induced oral carcinogenesis. The well-known chemical carcinogen 4NQO (50 ppm) was used to induce oral carcinogenesis through drinking water for 4, 12, and 20 weeks. The degree of cancer progression at each stage was confirmed by histological examination. At the end of the experimental period, 100% tumor formation was observed in the oral cavity of 4NQO induced animals with significant (P<0.05) alteration in the status of tumor markers, tongue and liver phase I and phase II drug metabolizing enzymes indicating progression of disease. Oral administration of geraniol at the dose of 200 mg/kg b.wt., thrice a week to 4NQO induced animals was able to inhibit tumor formation and thereby delayed the progression of oral carcinogenesis by modulating tongue and liver phase I and phase II drug metabolizing enzymes, as substantiated further by the histological and transmission electron microscopic studies. Our results demonstrate that geraniol exerts its chemopreventive potential by altering activities of phases I and II drug metabolizing enzymes to achieve minimum bioactivation of carcinogen and maximum detoxification. Copyright © 2013 Elsevier B.V. All rights reserved.
Antinociceptive activity of Riparin II from Aniba riparia: Further elucidation of the possible mechanisms.

PubMed

Rodrigues de Carvalho, Alyne Mara; Vasconcelos, Leonardo Freire; Moura Rocha, Nayrton Flávio; Vasconcelos Rios, Emiliano Ricardo; Dias, Marília Leite; Maria de França Fonteles, Marta; Gaspar, Danielle Macêdo; Barbosa Filho, José Maria; Chavez Gutierrez, Stanley Juan; Florenço de Sousa, Francisca Cléa

2018-05-01

Riparin II (RipII) has an anti-inflammatory activity potentially due its ability to decrease TNF-α and IL-1β production and its histamine antagonism. The objective of this study was to evaluate the role of RipII in the pain process and the possible antinociceptive mechanisms involved, using classic models of nociception. Male Swiss mice were used in the assays. Determinate the acute toxicity according to the OECD 425 test guideline. The models used were the acetic acid-, formalin-, hot plate and glutamate-induced nociception. For evaluation of antinociceptive effect, the involvement of TRPV1, TRPA1, TRPM8, ASICS, Bradykinin, PKC and PKA were performed using the paw licking using agonists. The acute toxicity study did not detect any clinical signs or changes in behavior or mortality. RipII, administered orally (25 and 50 mg/kg) caused a reduction of nociception induced by acetic acid, formalin (on the second phase) and glutamate. In the investigation of antinociceptive mechanism, we used capsaicin (2.2 μg/paw), cinnamaldehyde (10 nmol/paw), menthol (1.2 μmol/paw), ASICS (2% acetic acid, pH 1.98) and bradykinin (10 μg/paw). The results showed that TRPV1, TRPA1, TRPM8, ASICS and bradykinin play a role in the antinociceptive effect of RipII. The results also showed that PKA is involved too. These data demonstrate that RipII has a low or not toxicity and produced an important antinociceptive effect through mechanisms that probably involve an interaction, at least in part, TRPV1, TRPA1, TRPM8, ASICS, bradykinin and PKA participate in the RipII's antinociceptive effect. Copyright © 2018 Elsevier B.V. All rights reserved.
Quaternary arrangement of an active, native group II intron ribonucleoprotein complex revealed by small-angle X-ray scattering.

PubMed

Gupta, Kushol; Contreras, Lydia M; Smith, Dorie; Qu, Guosheng; Huang, Tao; Spruce, Lynn A; Seeholzer, Steven H; Belfort, Marlene; Van Duyne, Gregory D

2014-04-01

The stable ribonucleoprotein (RNP) complex formed between the Lactococcus lactis group II intron and its self-encoded LtrA protein is essential for the intron's genetic mobility. In this study, we report the biochemical, compositional, hydrodynamic and structural properties of active group II intron RNP particles (+A) isolated from its native host using a novel purification scheme. We employed small-angle X-ray scattering to determine the structural properties of these particles as they exist in solution. Using sucrose as a contrasting agent, we derived a two-phase quaternary model of the protein-RNA complex. This approach revealed that the spatial properties of the complex are largely defined by the RNA component, with the protein dimer located near the center of mass. A transfer RNA fusion engineered into domain II of the intron provided a distinct landmark consistent with this interpretation. Comparison of the derived +A RNP shape with that of the previously reported precursor intron (ΔA) particle extends previous findings that the loosely packed precursor RNP undergoes a dramatic conformational change as it compacts into its active form. Our results provide insights into the quaternary arrangement of these RNP complexes in solution, an important step to understanding the transition of the group II intron from the precursor to a species fully active for DNA invasion.
RNA Polymerase II Regulates Topoisomerase 1 Activity to Favor Efficient Transcription.

PubMed

Baranello, Laura; Wojtowicz, Damian; Cui, Kairong; Devaiah, Ballachanda N; Chung, Hye-Jung; Chan-Salis, Ka Yim; Guha, Rajarshi; Wilson, Kelli; Zhang, Xiaohu; Zhang, Hongliang; Piotrowski, Jason; Thomas, Craig J; Singer, Dinah S; Pugh, B Franklin; Pommier, Yves; Przytycka, Teresa M; Kouzine, Fedor; Lewis, Brian A; Zhao, Keji; Levens, David

2016-04-07

We report a mechanism through which the transcription machinery directly controls topoisomerase 1 (TOP1) activity to adjust DNA topology throughout the transcription cycle. By comparing TOP1 occupancy using chromatin immunoprecipitation sequencing (ChIP-seq) versus TOP1 activity using topoisomerase 1 sequencing (TOP1-seq), a method reported here to map catalytically engaged TOP1, TOP1 bound at promoters was discovered to become fully active only after pause-release. This transition coupled the phosphorylation of the carboxyl-terminal-domain (CTD) of RNA polymerase II (RNAPII) with stimulation of TOP1 above its basal rate, enhancing its processivity. TOP1 stimulation is strongly dependent on the kinase activity of BRD4, a protein that phosphorylates Ser2-CTD and regulates RNAPII pause-release. Thus the coordinated action of BRD4 and TOP1 overcame the torsional stress opposing transcription as RNAPII commenced elongation but preserved negative supercoiling that assists promoter melting at start sites. This nexus between transcription and DNA topology promises to elicit new strategies to intercept pathological gene expression. Copyright © 2016 Elsevier Inc. All rights reserved.
Nucleoside-2',3'/3',5'-bis(thio)phosphate antioxidants are also capable of disassembly of amyloid beta42-Zn(ii)/Cu(ii) aggregates via Zn(ii)/Cu(ii)-chelation.

PubMed

Hevroni, Bosmat Levi; Major, Dan Thomas; Dixit, Mudit; Mhashal, Anil Ranu; Das, Susanta; Fischer, Bilha

2016-05-18

Currently, there is an urgent need for biocompatible metal-ion chelators capable of antioxidant activity and disassembly of amyloid beta (Aβ)-aggregates as potential therapeutics for Alzheimer's disease (AD). We recently demonstrated the promising antioxidant activity of adenine/guanine 2',3' or 3',5'-bis(thio)phosphate analogues, 2'-dA/G3'5'PO/S and A2'3'PO/S, and their affinity to Zn(ii)-ions. These findings encouraged us to evaluate them as agents for the dissolution of Aβ42-Zn(ii)/Cu(ii) aggregates. Specifically, we explored their ability to bind Cu(ii)/Zn(ii)-ions, the geometry and stoichiometry of these complexes, Cu(ii)/Zn(ii)-binding-sites and binding mode, and the ability of these analogues to dissolve Aβ42-Zn(ii)/Cu(ii) aggregates, as well as their effect on the secondary structure of those aggregates. Finally, we identified the most promising agents for dissolution of Aβ42-Zn(ii)/Cu(ii) aggregates. Specifically, we observed the formation of a 1 : 1 complex between 2'-dG3'5'PO and Cu(ii), involving O4 ligands. Zn(ii) was coordinated by both thiophosphate groups of 2'-dA3'5'PS and A2'3'PS involving O2S2 ligands in a 1 : 1 stoichiometry. A2'3'PS dissolves Aβ42-Zn(ii) and Aβ42-Cu(ii) aggregates as effectively as, and 2.5-fold more effectively than EDTA, respectively. Furthermore, 2'-dG3'5'PS and A2'3'PS reverted the Aβ42-M(ii) structure, back to that of the free Aβ42. Finally, cryo-TEM and TEM images confirmed the disassembly of Aβ42 and Aβ42-M(ii) aggregates by A2'3'PS. Hence, 2'-dG3'5'PS and A2'3'PS may serve as promising scaffolds for new AD therapeutics, acting as both effective antioxidants and agents for solubilization of Aβ42-Cu(ii)/Zn(ii) aggregates.
8 CFR 329.5 - Natives of the Philippines with active duty service during World War II.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Natives of the Philippines with active duty service during World War II. 329.5 Section 329.5 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY NATIONALITY REGULATIONS SPECIAL CLASSES OF PERSONS WHO MAY BE NATURALIZED: NATURALIZATION BASED UPON ACTIVE DUTY SERVICE IN THE UNITED STATES...
Synthesis, spectral, antitumor, antioxidant and antimicrobial studies on Cu(II), Ni(II) and Co(II) complexes of 4-[(1H-Benzoimidazol-2-ylimino)-methyl]-benzene-1,3-diol.

PubMed

El-wakiel, Nadia; El-keiy, Mai; Gaber, Mohamed

2015-08-05

A new Schiff base of 2-aminobenzimidazole with 2,4-dihydroybezaldehyde (H₃L), and its Cu(II), Ni(II) and Co(II) complexes have been synthesized and characterized by elemental analyses, molar conductance, thermal analysis (TGA), inductive coupled plasma (ICP), magnetic moment measurements, IR, EI-mass, UV-Vis. and ESR spectral studies. On the basis of spectral studies and analytical data, it is evident that the Schiff base acts as dibasic tridentate ligand coordinating via deprotonated OH, NH and azomethine nitrogen atom. The results showed that Co(II) and Ni(II) complexes have tetrahedral structure while Cu(II) complexes has octahedral geometry. The kinetic and thermodynamic parameters of the thermal decomposition stages have been evaluated. The studied complexes were tested for their in vitro antimicrobial activities against some bacterial strains. The anticancer activity of the ligand and its metal complexes is evaluated against human liver Carcinoma (HEPG2) cell. These compounds exhibited a moderate and weak activity against the tested HEPG2 cell lines with IC₅₀ of 9.08, 18.2 and 19.7 μg/ml for ligand, Cu(II) and Ni(II) complexes, respectively. In vitro antioxidant activity of the newly synthesized compounds has also been evaluated. Copyright © 2015 Elsevier B.V. All rights reserved.
A Novel Apolipoprotein C-II Mimetic Peptide That Activates Lipoprotein Lipase and Decreases Serum Triglycerides in Apolipoprotein E–Knockout Mice

PubMed Central

Sakurai, Toshihiro; Sakurai-Ikuta, Akiko; Sviridov, Denis; Freeman, Lita; Ahsan, Lusana; Remaley, Alan T.

2015-01-01

Apolipoprotein A-I (apoA-I) mimetic peptides are currently being developed as possible new agents for the treatment of cardiovascular disease based on their ability to promote cholesterol efflux and their other beneficial antiatherogenic properties. Many of these peptides, however, have been reported to cause transient hypertriglyceridemia due to inhibition of lipolysis by lipoprotein lipase (LPL). We describe a novel bihelical amphipathic peptide (C-II-a) that contains an amphipathic helix (18A) for binding to lipoproteins and stimulating cholesterol efflux as well as a motif based on the last helix of apolipoprotein C-II (apoC-II) that activates lipolysis by LPL. The C-II-a peptide promoted cholesterol efflux from ATP-binding cassette transporter ABCA1-transfected BHK cells similar to apoA-I mimetic peptides. Furthermore, it was shown in vitro to be comparable to the full-length apoC-II protein in activating lipolysis by LPL. When added to serum from a patient with apoC-II deficiency, it restored normal levels of LPL-induced lipolysis and also enhanced lipolysis in serum from patients with type IV and V hypertriglyceridemia. Intravenous injection of C-II-a (30 mg/kg) in apolipoprotein E–knockout mice resulted in a significant reduction of plasma cholesterol and triglycerides of 38 ± 6% and 85 ± 7%, respectively, at 4 hours. When coinjected with the 5A peptide (60 mg/kg), the C-II-a (30 mg/kg) peptide was found to completely block the hypertriglyceridemic effect of the 5A peptide in C57Bl/6 mice. In summary, C-II-a is a novel peptide based on apoC-II, which promotes cholesterol efflux and lipolysis and may therefore be useful for the treatment of apoC-II deficiency and other forms of hypertriglyceridemia. PMID:25395590
Synthesis, spectroscopic characterization, in-vitro antibacterial and antiproliferative activities of some metal(II) complexes of 3,4-dihydronaphthalen-1(2H)-one Schiff base

PubMed Central

Osowole, Aderoju Amoke

2012-01-01

The Schiff base, 3-hydroxy-4-{[4-(methylsulfanyl)phenyl]imino}-3,4-dihydronaphthalen-1(2H)-one, and its Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Pd(II) complexes have been synthesized and characterized by microanalysis, conductance, 1H NMR, infrared and electronic spectral measurements. The ligand exists in the ketoimine form in chloroform, and in the enolimine form in the solid state, as shown by 1H NMR and IR spectroscopies. The ligand coordinates to the metal ions in the ratio 1:1, using NO chromophores forming complexes of the type [MLNO3]H2O, with the exception of the Zn(II) and Pd(II) complexes. Electronic measurements are indicative of a four coordinate square-planar geometry for all the complexes, except for the Cu(II) and Zn(II) complexes which assume a tetrahedral geometry. None is an electrolyte in nitromethane. The ligand and the metal complexes are air-stable, but decomposed on heating at 120 °C and in the range 150-156 °C respectively. The antibacterial studies reveal that the Co(II) and the Cu(II) complexes exhibit broad-spectrum activity against Proteus mirabilis, Escherichia coli and Staphylococcus aureus with inhibitory zones range of 14.0-22.0 and 13.0-25.0 mm respectively. The antiproliferative studies show that the Zn(II) complex has the best in-vitro anticancer activity against both HT-29 (colon) carcinoma and MCF-7 (human breast) adenocarcinoma with IC50 values of 6.46 µm and 3.19 µm, which exceeds the activity of Cis-platin by 8 % and 63 % respectively. PMID:27350773
Halo-substituted thiosemicarbazones and their copper(II), nickel(II) complexes: Detailed spectroscopic characterization and study of antitumour activity against HepG2 human hepatoblastoma cells

NASA Astrophysics Data System (ADS)

Jagadeesh, M.; Kalangi, Suresh K.; Sivarama Krishna, L.; Reddy, A. Varada

2014-01-01

Copper(II) and nickel(II) complexes of two different halogen substituted thiosemicarbazone ligands were synthesized. The ligands 3,4-difluoroacetophenone thiosemicarbazone (1) and 2-bromo-4'-chloroacetophenone thiosemicarbazone (2) were characterized and confirmed spectroscopically by FT-IR, FT-Raman, UV-vis and fluorescence spectral analysis, while the respective copper(II) complexes [Cu(C9H9N3F2S)2Cl2] (1a), [Cu(C9H9N3ClBrS)2Cl2] (2a) and nickel(II) complexes [Ni(C9H9N3F2S)2] (1b), [Ni(C9H9N3ClBrS)2] (2b) were characterized by FT-IR, UV-vis and electron paramagnetic spectroscopy (EPR). The EPR spectra of the Cu(II) complexes provided the rhombic octahedral and axial symmetry of the complexes 1a and 2a respectively. For the complex 1a, the g values calculated as g1 = 2.1228, g2 = 2.0706 and g3 = 2.001 between 2900 and 3300 G. While for the complex 2a, a set of two resonance absorptions were observed. The synthesized compounds were tested for antitumor activity and showed that the ability to kill liver cancer cells significantly. Out of all the synthesized compounds, copper(II) complexes 1a and 2a showed high cytotoxic effect on liver cancer cells with 67.51% and 42.77% of cytotoxicity respectively at 100 μM.
Protein kinase C epsilon mediates the inhibition of angiotensin II on the slowly activating delayed-rectifier potassium current through channel phosphorylation.

PubMed

Gou, Xiangbo; Wang, Wenying; Zou, Sihao; Qi, Yajuan; Xu, Yanfang

2018-03-01

The slowly activating delayed rectifier K + current (I Ks ) is one of the main repolarizing currents in the human heart. Evidence has shown that angiotensin II (Ang II) regulates I Ks through the protein kinase C (PKC) pathway, but the related results are controversial. This study was designed to identify PKC isoenzymes involved in the regulation of I Ks by Ang II and the underlying molecular mechanism. The whole-cell patch-clamp technique was used to record I Ks in isolated guinea pig ventricular cardiomyocytes and in human embryonic kidney (HEK) 293 cells co-transfected with human KCNQ1/KCNE1 genes and Ang II type 1 receptor genes. Ang II inhibited I Ks in a concentration-dependent manner in native cardiomyocytes. A broad PKC inhibitor Gö6983 (not inhibiting PKCε) and a selective cPKC inhibitor Gö6976 did not affect the inhibitory action of Ang II. In contrast, the inhibition was significantly attenuated by PKCε-selective peptide inhibitor εV1-2. However, direct activation of PKC by phorbol 12-myristate 13-acetate (PMA) increased the cloned human I Ks in HEK293 cells. Similarly, the cPKC peptide activator significantly enhanced the current. In contrast, the PKCε peptide activator inhibited the current. Further evidence showed that PKCε knockdown by siRNA antagonized the Ang II-induced inhibition on KCNQ1/KCNE1 current, whereas knockdown of cPKCs (PKCα and PKCβ) attenuated the potentiation of the current by PMA. Moreover, deletion of four putative phosphorylation sites in the C-terminus of KCNQ1 abolished the action of PMA. Mutation of two putative phosphorylation sites in the N-terminus of KCNQ1 and one site in KCNE1 (S102) blocked the inhibition of Ang II. Our results demonstrate that PKCε isoenzyme mediates the inhibitory action of Ang II on I Ks and by phosphorylating distinct sites in KCNQ1/KCNE1, cPKC and PKCε isoenzymes produce the contrary regulatory effects on the channel. These findings have provided new insight into the molecular mechanism
Immobilized copper(II) macrocyclic complex on MWCNTs with antibacterial activity

NASA Astrophysics Data System (ADS)

Tarlani, Aliakbar; Narimani, Khashayar; Mohammadipanah, Fatemeh; Hamedi, Javad; Tahermansouri, Hasan; Amini, Mostafa M.

2015-06-01

In a new approach, a copper(II) tetraaza macrocyclic complex (CuTAM) was covalently bonded on modified multi-walled carbon nanotubes (MWCNTs). To achieve this purpose, MWCNTs were converted to MWCNT-COCl and then reacted to NH groups of TAM ligand. The prepared material was characterized by Fourier Transform Infrared (FT-IR), X-ray diffraction (XRD), Raman spectroscopy, thermal gravimetric analysis (TGA), and FESEM (field emission scanning electron microscopy). FT-IR and TGA demonstrated the presence of the organic moieties, and XRD proved that the structure of MWCNTs remained intact during the three modification steps. An increase in the ID/IG ratio in Raman spectra confirmed the surface modifications. Finally, the samples were subjected to an antibacterial assessment to compare their biological activity. The antibacterial test showed that the grafted complex on the surface of the nanotube (MWCNT-CO-CuTAM) has higher antibacterial activity against Bacillus subtilis ATCC 6633 than the MWCNT-COOH and CuTAM with 1000 and 2000 μg/mL.
Skeletal muscle insulin resistance in salt-sensitive hypertension: role of angiotensin II activation of NFκB.

PubMed

Zhou, Ming-Sheng; Liu, Chang; Tian, Runxia; Nishiyama, Akira; Raij, Leopoldo

2015-05-01

We have previously shown that in hypertensive Dahl salt-sensitive (DS) rats, impaired endothelium-dependent relaxation to acetylcholine and to insulin is mechanistically linked to up-regulation of angiotensin (Ang) II actions and the production of reactive oxygen species (ROS) and to activation of the proinflammatory transcription factor (NF)κB. Here we investigated whether Ang II activation of NFκB contributed to insulin resistance in the skeletal muscle of this animal model. DS rats were fed either a normal (NS, 0.5% NaCl) or high (HS, 4% NaCl) salt diet for 6 weeks. In addition, 3 separate groups of HS rats were given angiotensin receptor 1 blocker candesartan (ARB, 10 mg/kg/day in drinking water), antioxidant tempol (1 mmol/L in drinking water) or NFκB inhibitor PDTC (150 mg/kg in drinking water). DS rats manifested an increase in soleus muscle Ang II content, ROS production and phosopho-IκBα/IκBα ratio, ARB or tempol reduced ROS and phospho-IκBα/IκBα ratio. Hypertensive DS rats also manifested a reduction in glucose infusion rate, impaired insulin-induced Akt phosphorylation and Glut-4 translocation in the soleus muscle, which were prevented with treatment of either ARB, tempol, or PDTC. Data from the rat diabetes signaling pathway PCR array showed that 8 genes among 84 target genes were altered in the muscle of hypertensive rats with the increase in gene expression of ACE1 and 5 proinflammatory genes, and decrease of 2 glucose metabolic genes. Incubation of the muscle with NFκB SN50 (a specific peptide inhibitor of NFκB) ex vivo reversed changes in hypertension-induced gene expression. The current findings strongly suggest that the activation of NFκB inflammatory pathway by Ang II play a critical role in skeletal muscle insulin resistance in salt-sensitive hypertension.
Structural analysis of group II chitinase (ChtII) catalysis completes the puzzle of chitin hydrolysis in insects.

PubMed

Chen, Wei; Qu, Mingbo; Zhou, Yong; Yang, Qing

2018-02-23

Chitin is a linear homopolymer of N -acetyl-β-d-glucosamines and a major structural component of insect cuticles. Chitin hydrolysis involves glycoside hydrolase family 18 (GH18) chitinases. In insects, chitin hydrolysis is essential for periodic shedding of the old cuticle ecdysis and proceeds via a pathway different from that in the well studied bacterial chitinolytic system. Group II chitinase (ChtII) is a widespread chitinolytic enzyme in insects and contains the greatest number of catalytic domains and chitin-binding domains among chitinases. In Lepidopterans, ChtII and two other chitinases, ChtI and Chi-h, are essential for chitin hydrolysis. Although ChtI and Chi-h have been well studied, the role of ChtII remains elusive. Here, we investigated the structure and enzymology of Of ChtII, a ChtII derived from the insect pest Ostrinia furnacalis We present the crystal structures of two catalytically active domains of Of ChtII, Of ChtII-C1 and Of ChtII-C2, both in unliganded form and complexed with chitooligosaccharide substrates. We found that Of ChtII-C1 and Of ChtII-C2 both possess long, deep substrate-binding clefts with endochitinase activities. Of ChtII exhibited structural characteristics within the substrate-binding cleft similar to those in Of Chi-h and Of ChtI. However, Of ChtII lacked structural elements favoring substrate binding beyond the active sites, including an extra wall structure present in Of Chi-h. Nevertheless, the numerous domains in Of ChtII may compensate for this difference; a truncation containing one catalytic domain and three chitin-binding modules ( Of ChtII-B4C1) displayed activity toward insoluble polymeric substrates that was higher than those of Of Chi-h and Of ChtI. Our observations provide the last piece of the puzzle of chitin hydrolysis in insects. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.
Preconcentration of Sn (II) using the methylene blue on the activated carbon and its determination by spectrophotometry method.

PubMed

Khodadoust, Saeid; Cham Kouri, Narges

2014-04-05

A simple and accurate spectrophotometric method for determination of trace amounts of Sn (II) ion in soil sample was developed by using the methylene blue (MB) in the presence of activated carbon (AC) as the adsorbent Solid Phase Extraction (SPE) of Sn (II) and then determined by UV-Vis. The Beer's law is obeyed over the concentration range of 1-80ngmL(-1) of Sn (II) with the detection limits of 0.34ngmL(-1). The influence of type and volume of eluent, concentration of MB, pH, and amount of AC on sensitivity of spectrophotometric method were optimized. The method has been successfully applied for Sn (II) ion determination in soil sample. Copyright © 2013 Elsevier B.V. All rights reserved.
Mediator, TATA-binding Protein, and RNA Polymerase II Contribute to Low Histone Occupancy at Active Gene Promoters in Yeast*

PubMed Central

Ansari, Suraiya A.; Paul, Emily; Sommer, Sebastian; Lieleg, Corinna; He, Qiye; Daly, Alexandre Z.; Rode, Kara A.; Barber, Wesley T.; Ellis, Laura C.; LaPorta, Erika; Orzechowski, Amanda M.; Taylor, Emily; Reeb, Tanner; Wong, Jason; Korber, Philipp; Morse, Randall H.

2014-01-01

Transcription by RNA polymerase II (Pol II) in eukaryotes requires the Mediator complex, and often involves chromatin remodeling and histone eviction at active promoters. Here we address the role of Mediator in recruitment of the Swi/Snf chromatin remodeling complex and its role, along with components of the preinitiation complex (PIC), in histone eviction at inducible and constitutively active promoters in the budding yeast Saccharomyces cerevisiae. We show that recruitment of the Swi/Snf chromatin remodeling complex to the induced CHA1 promoter, as well as its association with several constitutively active promoters, depends on the Mediator complex but is independent of Mediator at the induced MET2 and MET6 genes. Although transcriptional activation and histone eviction at CHA1 depends on Swi/Snf, Swi/Snf recruitment is not sufficient for histone eviction at the induced CHA1 promoter. Loss of Swi/Snf activity does not affect histone occupancy of several constitutively active promoters; in contrast, higher histone occupancy is seen at these promoters in Mediator and PIC component mutants. We propose that an initial activator-dependent, nucleosome remodeling step allows PIC components to outcompete histones for occupancy of promoter sequences. We also observe reduced promoter association of Mediator and TATA-binding protein in a Pol II (rpb1-1) mutant, indicating mutually cooperative binding of these components of the transcription machinery and indicating that it is the PIC as a whole whose binding results in stable histone eviction. PMID:24727477

Activation of Group II Metabotropic Glutamate Receptors Induces Depotentiation in Amygdala Slices and Reduces Fear-Potentiated Startle in Rats

ERIC Educational Resources Information Center

Lin, Chia-Ho; Lee, Chia-Ching; Huang, Ya-Chun; Wang, Su-Jane; Gean, Po-Wu

2005-01-01

There is a close correlation between long-term potentiation (LTP) in the synapses of lateral amygdala (LA) and fear conditioning in animals. We predict that reversal of LTP (depotentiation) in this area of the brain may ameliorate conditioned fear. Activation of group II metabotropic glutamate receptors (mGluR II) with DCG-IV induces…
FISPACT-II: An Advanced Simulation System for Activation, Transmutation and Material Modelling

NASA Astrophysics Data System (ADS)

Sublet, J.-Ch.; Eastwood, J. W.; Morgan, J. G.; Gilbert, M. R.; Fleming, M.; Arter, W.

2017-01-01

Fispact-II is a code system and library database for modelling activation-transmutation processes, depletion-burn-up, time dependent inventory and radiation damage source terms caused by nuclear reactions and decays. The Fispact-II code, written in object-style Fortran, follows the evolution of material irradiated by neutrons, alphas, gammas, protons, or deuterons, and provides a wide range of derived radiological output quantities to satisfy most needs for nuclear applications. It can be used with any ENDF-compliant group library data for nuclear reactions, particle-induced and spontaneous fission yields, and radioactive decay (including but not limited to TENDL-2015, ENDF/B-VII.1, JEFF-3.2, JENDL-4.0u, CENDL-3.1 processed into fine-group-structure files, GEFY-5.2 and UKDD-16), as well as resolved and unresolved resonance range probability tables for self-shielding corrections and updated radiological hazard indices. The code has many novel features including: extension of the energy range up to 1 GeV; additional neutron physics including self-shielding effects, temperature dependence, thin and thick target yields; pathway analysis; and sensitivity and uncertainty quantification and propagation using full covariance data. The latest ENDF libraries such as TENDL encompass thousands of target isotopes. Nuclear data libraries for Fispact-II are prepared from these using processing codes PREPRO, NJOY and CALENDF. These data include resonance parameters, cross sections with covariances, probability tables in the resonance ranges, PKA spectra, kerma, dpa, gas and radionuclide production and energy-dependent fission yields, supplemented with all 27 decay types. All such data for the five most important incident particles are provided in evaluated data tables. The Fispact-II simulation software is described in detail in this paper, together with the nuclear data libraries. The Fispact-II system also includes several utility programs for code-use optimisation
Postsynaptic and presynaptic group II metabotropic glutamate receptor activation reduces neuronal excitability in rat midline paraventricular thalamic nucleus.

PubMed

Hermes, M L H J; Renaud, L P

2011-03-01

Drugs that interact with group II metabotropic glutamate receptors (mGluRs) are presently being evaluated for a role in the treatment of anxiety disorders and symptoms of schizophrenia. Their mechanism of action is believed to involve a reduction in excitatory neurotransmission in limbic and forebrain regions commonly associated with these mental disorders. In rodents, the glutamatergic neurons in the midline paraventricular thalamic nucleus (PVT) provide excitatory inputs to the limbic system and forebrain. PVT also displays a high density of group II mGluRs, predominantly the metabotropic glutamate 2 receptor (mGluR2). Because the role of group II mGluRs in regulating cellular and synaptic excitability in this location has yet to be determined, we used whole-cell patch-clamp recording and acute rat brain slice preparations to evaluate PVT neuron responses to a selective group II mGluR agonist, (1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY 379268). LY 379268 consistently induced membrane hyperpolarization and suppressed firing by postsynaptic receptor-mediated activation of a barium-sensitive background K(+) conductance. This effect could be blocked by (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl)propanoic acid (LY 341495), a selective group II mGluR antagonist. In addition, LY 379268 acted at presynaptic receptors to reduce ionotropic glutamate receptor-mediated excitatory synaptic transmission. An mGluR2-positive allosteric modulator, 2,2,2-trifluoro-N-[4-(2-methoxyphenoxy)phenyl]-N-(3-pyridinylmethyl)ethanesulfonamide hydrochloride (LY 487379), resulted in leftward shifts of the LY 379268 dose-response curve for both postsynaptic and presynaptic actions. The data demonstrate that activation of postsynaptic and presynaptic group II (presumably mGluR2) mGluRs reduces neuronal excitability in midline thalamus, an action that may contribute to the effectiveness of mGluR2-activating drugs in rodent models of anxiety and
c-Jun binds the N terminus of human TAF(II)250 to derepress RNA polymerase II transcription in vitro.

PubMed

Lively, T N; Ferguson, H A; Galasinski, S K; Seto, A G; Goodrich, J A

2001-07-06

c-Jun is an oncoprotein that activates transcription of many genes involved in cell growth and proliferation. We studied the mechanism of transcriptional activation by human c-Jun in a human RNA polymerase II transcription system composed of highly purified recombinant and native transcription factors. Transcriptional activation by c-Jun depends on the TATA-binding protein (TBP)-associated factor (TAF) subunits of transcription factor IID (TFIID). Protein-protein interaction assays revealed that c-Jun binds with high specificity to the largest subunit of human TFIID, TAF(II)250. The region of TAF(II)250 bound by c-Jun lies in the N-terminal 163 amino acids. This same region of TAF(II)250 binds to TBP and represses its interaction with TATA boxes, thereby decreasing DNA binding by TFIID. We hypothesized that c-Jun is capable of derepressing the effect of the TAF(II)250 N terminus on TFIID-driven transcription. In support of this hypothesis, we found that c-Jun increased levels of TFIID-driven transcription in vitro when added at high concentrations to a DNA template lacking activator protein 1 (AP-1) sites. Moreover, c-Jun blocked the repression of TBP DNA binding caused by the N terminus of TAF(II)250. In addition to revealing a mechanism by which c-Jun activates transcription, our studies provide the first evidence that an activator can bind directly to the N terminus of TAF(II)250 to derepress RNA polymerase II transcription in vitro.
Synthesis, characterization and properties of some divalent metal(II) complexes: Their electrochemical, catalytic, thermal and antimicrobial activity studies

NASA Astrophysics Data System (ADS)

Tümer, Mehmet; Ekinci, Duygu; Tümer, Ferhan; Bulut, Akif

2007-07-01

In this study, we synthesized the amine compound 2-(2-aminoethyliminomethyl)phenol (H 3A) as the starting material, and then we prepared the polydentate Schiff base ligands from the reactions of the amine compound (H 3A) with phtaldialdehyde (H 2L), 4-methyl-2,6-di-formlyphenol (H 3L 1) and 4- t-butyl-2,6-di-formylphenol (H 3L 2) in the ethanol solution. Moreover, the complexes Cd(II), Cu(II), Co(II), Ni(II), Zn(II) and Sn(II) of the ligands H 2L, H 3L 1 and H 3L 2 have been prepared. All compounds have been characterized by the analytical and spectroscopic methods. In addition, the magnetic susceptibility and molar conductance measurements have been made. The catalytic properties of the mono- and binuclear Co(II) and Cu(II) complexes have been studied on the 3,5-di- tert-butylcatechol (3,5-DTBC) and ascorbic acid (aa) as a substrate. The oxidative C-C coupling properties of the Co(II) and Cu(II) complexes have been investigated on the sterically hindered 2,6-di- tert-butylphenol (dtbp). The antimicrobial activity properties of the ligands and their mono- and binuclear complexes have been studied against the bacteria and fungi. The results have been compared to the antibacterial and fungi drugs. The TGA curves show that the decomposition takes place in three steps for all complexes. Electrochemical properties of the complexes Cu(II) and Ni(II) have been investigated for the first time in acetonitrile by cyclic voltammetry.
Synthesis, structural studies and antimicrobial activity of N'-((2Z, 3E)-3-(hydroxyimino)butan-2-ylidene)-2-phenylacetohydrazide and its Co(II), Ni(II) complexes

NASA Astrophysics Data System (ADS)

Karadeniz, Şeyma; Ataol, Cigdem Yuksektepe; Şahin, Onur; İdil, Önder; Bati, Hümeyra

2018-06-01

A new aroylhydrazoneoxime, N'-((2Z, 3E)-3-(hydroxyimino)butan-2-ylidene)-2-phenylacetohydrazide ligand (LH2) and its Ni(II) and Co(II) complexes, have been synthesized and characterized by elemental and thermal analyses, IR and UV-vis spectroscopy, magnetic moment and X-ray diffraction. The antimicrobial activities of these compounds were tested by using minimal inhibitory concentration method (MIC). The ligand-containing aroylhydrazone and oxime groups and its Ni complex crystallize in the triclinic system and P 1 - space group, while its Co complex crystallizes in the monoclinic system and the C 2/c space group. X-ray results show that the ligand in the keto form is transformed into enolic form when it forms coordination. From elemental analysis data, the stoichiometry of Co(II) complex was found to be 1:2 (metal/ligand), but 1:1 for Ni(II). IR spectra indicate that the ligand acts as monoanionic NNO- tridentate and coordination takes place form through the oxime nitrogen, imine nitrogen, and enolate oxygen atoms.
Biosorption of lead (II) ions by NaOH-activated apple (Malus domestica) juice residue

NASA Astrophysics Data System (ADS)

Arimurti, Devita Dwi; Heraldy, Eddy; Lestari, Witri Wahyu

2016-02-01

This research studied the removal of Pb(II) ions from aqueous solutions using NaOH-activated apple (Malus domestica) juice residue. Biosorbent was characterized with Fourier Transform Infrared Spectrophotometer (FTIR), and Surface Area Analyzer (SAA). The effects of biosorbent dosage, pH, contact time and initial metal ion concentration had been investigated in batch-adsorption method. The biosorption kinetic data were analyzed by pseudo-first-order and pseudo-second-order kinetics model. Freundlich and Langmuir's isotherm were used to describe the biosorption process. The optimum conditions of Pb(II) adsorption was observed at 60 min of contact time, pH 4, and 0.1 g biosorbent dosage in 25 ml solution. The biosorption kinetics followed the pseudo-second-order kinetic model, resulted biosorption constant rate of 0.184 g.mg-1.min-1. The Langmuir isotherm model exhibited the best fit to experimental data. The maximum biosorption capacity of Pb(II) determined according to the Langmuir model was 90.90 mg.g-1 at 302 K, with the adsorption energy of 26.429 kJ.mol-1.
MHC Class II Activation and Interferon-γ Mediate the Inhibition of Neutrophils and Eosinophils by Staphylococcal Enterotoxin Type A (SEA).

PubMed

Ferreira-Duarte, Ana P; Pinheiro-Torres, Anelize S; Anhê, Gabriel F; Condino-Neto, Antônio; Antunes, Edson; DeSouza, Ivani A

2017-01-01

Staphylococcal enterotoxins are classified as superantigens that act by linking T-cell receptor with MHC class II molecules, which are expressed on classical antigen-presenting cells (APC). Evidence shows that MHC class II is also expressed in neutrophils and eosinophils. This study aimed to investigate the role of MHC class II and IFN-γ on chemotactic and adhesion properties of neutrophils and eosinophils after incubation with SEA. Bone marrow (BM) cells obtained from BALB/c mice were resuspended in culture medium, and incubated with SEA (3-30 ng/ml; 1-4 h), after which chemotaxis and adhesion were evaluated. Incubation with SEA significantly reduced the chemotactic and adhesive responses in BM neutrophils activated with IL-8 (200 ng/ml). Likewise, SEA significantly reduced the chemotactic and adhesive responses of BM eosinophils activated with eotaxin (300 ng/ml). The inhibitory effects of SEA on cell chemotaxis and adhesion were fully prevented by prior incubation with an anti-MHC class II blocking antibody (2 μg/ml). SEA also significantly reduced the intracellular Ca 2+ levels in IL-8- and eotaxin-activated BM cells. No alterations of MAC-1, VLA4, and LFA-1α expressions were observed after SEA incubation. In addition, SEA elevated by 3.5-fold ( P < 0.05) the INF-γ levels in BM cells. Incubation of BM leukocytes with IFN-γ (10 ng/ml, 2 h) reduced both neutrophil and eosinophil chemotaxis and adhesion, which were prevented by prior incubation with anti-MHC class II antibody (2 μg/ml). In conclusion, SEA inhibits neutrophil and eosinophil by MHC class II-dependent mechanism, which may be modulated by concomitant release of IFN-γ.
Nickel(II) biosorption by Rhodotorula glutinis.

PubMed

Suazo-Madrid, Alicia; Morales-Barrera, Liliana; Aranda-García, Erick; Cristiani-Urbina, Eliseo

2011-01-01

The present study reports the feasibility of using Rhodotorula glutinis biomass as an alternative low-cost biosorbent to remove Ni(II) ions from aqueous solutions. Acetone-pretreated R. glutinis cells showed higher Ni(II) biosorption capacity than untreated cells at pH values ranging from 3 to 7.5, with an optimum pH of 7.5. The effects of other relevant environmental parameters, such as initial Ni(II) concentration, shaking contact time and temperature, on Ni(II) biosorption onto acetone-pretreated R. glutinis were evaluated. Significant enhancement of Ni(II) biosorption capacity was observed by increasing initial metal concentration and temperature. Kinetic studies showed that the kinetic data were best described by a pseudo-second-order kinetic model. Among the two-, three-, and four-parameter isotherm models tested, the Fritz-Schluender model exhibited the best fit to experimental data. Thermodynamic parameters (activation energy, and changes in activation enthalpy, activation entropy, and free energy of activation) revealed that the biosorption of Ni(II) ions onto acetone-pretreated R. glutinis biomass is an endothermic and non-spontaneous process, involving chemical sorption with weak interactions between the biosorbent and Ni(II) ions. The high sorption capacity (44.45 mg g(-1) at 25°C, and 63.53 mg g(-1) at 70°C) exhibited by acetone-pretreated R. glutinis biomass places this biosorbent among the best adsorbents currently available for removal of Ni(II) ions from aqueous effluents.
Synthesis, spectral characterization and catalytic activity of Co(II) complexes of drugs: crystal structure of Co(II)-trimethoprim complex.

PubMed

Madhupriya, Selvaraj; Elango, Kuppanagounder P

2014-01-24

New Co(II) complexes with drugs such as trimethoprim (TMP), cimetidine (CTD), niacinamide (NAM) and ofloxacin (OFL) as ligands were synthesized. The complexes were characterized by analytical analysis, various spectral techniques such as FT-IR, UV-Vis, magnetic measurements and molar conductivity. The magnetic susceptibility results coupled with the electronic spectra suggested a tetrahedral geometry for the complexes. The coordination mode of trimethoprim ligand and geometry of the complex were confirmed by single crystal X-ray studies. In this complex the metal ion possesses a tetrahedral geometry with two nitrogen atom from two TMP ligands and two chloride ions coordinated to it. The catalytic activity of the complexes in aryl-aryl coupling reaction was screened and the results indicated that among the four complexes [Co(OFL)Cl(H2O)] exhibited excellent catalytic activity. Copyright © 2013 Elsevier B.V. All rights reserved.
Structure and spectroscopic investigations of a bi-dentate N‧-[(4-ethylphenyl)methylidene]-4-hydroxybenzohydrazide and its Co(II), Ni(II), Cu(II) and Cd(II) complexes: Insights relevant to biological properties

NASA Astrophysics Data System (ADS)

Gopal Reddy, N. B.; Krishna, P. Murali; Shantha Kumar, S. S.; Patil, Yogesh P.; Nethaji, Munirathinam

2017-06-01

The present paper describes the synthesis of novel ligand, N‧-[(4-ethylphenyl)methylidene]-4-hydroxy benzohydrazide (HL) and its Co(II), Ni(II), Cu(II) and Cd(II) complexes. The ligand (HL) crystallizes in orthorhombic lattice in P212121 space group with a = 7.9941 (7) Å, b = 11.6154 (10) Å, c = 15.2278 (13) Å, α = β = γ = 90°. Spectroscopic data gives the strong evidence that ligand is coordinated through azomethine nitrogen and enolic oxygen with metal ion. The DNA binding studies revealed that the complexes bind to CT-DNA via intercalation/electrostatic interaction. All the targeted compounds showed more pronounced DNA cleavage activity in the presence of H2O2 and also inhibit the growth of in vitro antibacterial activity against Gram-positive and Gram-negative bacteria.
Optimizing Cu(II) removal from aqueous solution by magnetic nanoparticles immobilized on activated carbon using Taguchi method.

PubMed

Ebrahimi Zarandi, Mohammad Javad; Sohrabi, Mahmoud Reza; Khosravi, Morteza; Mansouriieh, Nafiseh; Davallo, Mehran; Khosravan, Azita

2016-01-01

This study synthesized magnetic nanoparticles (Fe(3)O(4)) immobilized on activated carbon (AC) and used them as an effective adsorbent for Cu(II) removal from aqueous solution. The effect of three parameters, including the concentration of Cu(II), dosage of Fe(3)O(4)/AC magnetic nanocomposite and pH on the removal of Cu(II) using Fe(3)O(4)/AC nanocomposite were studied. In order to examine and describe the optimum condition for each of the mentioned parameters, Taguchi's optimization method was used in a batch system and L9 orthogonal array was used for the experimental design. The removal percentage (R%) of Cu(II) and uptake capacity (q) were transformed into an accurate signal-to-noise ratio (S/N) for a 'larger-the-better' response. Taguchi results, which were analyzed based on choosing the best run by examining the S/N, were statistically tested using analysis of variance; the tests showed that all the parameters' main effects were significant within a 95% confidence level. The best conditions for removal of Cu(II) were determined at pH of 7, nanocomposite dosage of 0.1 gL(-1) and initial Cu(II) concentration of 20 mg L(-1) at constant temperature of 25 °C. Generally, the results showed that the simple Taguchi's method is suitable to optimize the Cu(II) removal experiments.
Calcium-manganese oxides as structural and functional models for active site in oxygen evolving complex in photosystem II: lessons from simple models.

PubMed

Najafpour, Mohammad Mahdi

2011-01-01

The oxygen evolving complex in photosystem II which induces the oxidation of water to dioxygen in plants, algae and certain bacteria contains a cluster of one calcium and four manganese ions. It serves as a model to split water by sunlight. Reports on the mechanism and structure of photosystem II provide a more detailed architecture of the oxygen evolving complex and the surrounding amino acids. One challenge in this field is the development of artificial model compounds to study oxygen evolution reaction outside the complicated environment of the enzyme. Calcium-manganese oxides as structural and functional models for the active site of photosystem II are explained and reviewed in this paper. Because of related structures of these calcium-manganese oxides and the catalytic centers of active site of the oxygen evolving complex of photosystem II, the study may help to understand more about mechanism of oxygen evolution by the oxygen evolving complex of photosystem II. Copyright © 2010 Elsevier B.V. All rights reserved.
A Nanostructured Lipid System as a Strategy to Improve the in Vitro Antibacterial Activity of Copper(II) Complexes.

PubMed

da Silva, Patricia B; Bonifácio, Bruna V; Frem, Regina C G; Godoy Netto, Adelino V; Mauro, Antonio E; Ferreira, Ana M da Costa; Lopes, Erica de O; Raddi, Maria S G; Bauab, Tais M; Pavan, Fernando R; Chorilli, Marlus

2015-12-16

The aim of this study was to construct a nanostructured lipid system as a strategy to improve the in vitro antibacterial activity of copper(II) complexes. New compounds with the general formulae [CuX₂(INH)₂]·nH₂O (X = Cl(-) and n = 1 (1); X = NCS(-) and n = 5 (2); X = NCO(-) and n = 4 (3); INH = isoniazid, a drug widely used to treat tuberculosis) derived from the reaction between the copper(II) chloride and isoniazid in the presence or absence of pseudohalide ions (NCS(-) or NCO(-)) were synthesized and characterized by infrared spectrometry, electronic absorption spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, elemental analysis, melting points and complexometry with 2,2',2'',2'''-(Ethane-1,2-diyldinitrilo)tetraacetic acid (EDTA). The characterization techniques allowed us to confirm the formation of the copper(II) complexes. The Cu(II) complexes were loaded into microemulsion (MEs) composed of 10% phase oil (cholesterol), 10% surfactant [soy oleate and Brij(®) 58 (1:2)] and 80% aqueous phase (phosphate buffer pH = 7.4) prepared by sonication. The Cu(II) complex-loaded MEs displayed sizes ranging from 158.0 ± 1.060 to 212.6 ± 1.539 nm, whereas the polydispersity index (PDI) ranged from 0.218 ± 0.007 to 0.284 ± 0.034. The antibacterial activity of the free compounds and those that were loaded into the MEs against Staphylococcus aureus ATCC(®) 25923 and Escherichia coli ATCC(®) 25922, as evaluated by a microdilution technique, and the cytotoxicity index (IC50) against the Vero cell line (ATCC(®) CCL-81(TM)) were used to calculate the selectivity index (SI). Among the free compounds, only compound 2 (MIC 500 μg/mL) showed activity for S. aureus. After loading the compounds into the MEs, the antibacterial activity of compounds 1, 2 and 3 was significantly increased against E. coli (MIC's 125, 125 and 500 μg/mL, respectively) and S. aureus (MICs 250, 500 and 125 μg/mL, respectively). The loaded compounds were less toxic against the
A Nanostructured Lipid System as a Strategy to Improve the in Vitro Antibacterial Activity of Copper(II) Complexes.

PubMed

Silva, Patricia B da; Bonifácio, Bruna V; Frem, Regina C G; Godoy Netto, Adelino V; Mauro, Antonio E; Ferreira, Ana M da Costa; Lopes, Erica de O; Raddi, Maria S G; Bauab, Tais M; Pavan, Fernando R; Chorilli, Marlus

2015-12-16

The aim of this study was to construct a nanostructured lipid system as a strategy to improve the in vitro antibacterial activity of copper(II) complexes. New compounds with the general formulae [CuX₂(INH)₂]·nH₂O (X = Cl(-) and n = 1 (1); X = NCS(-) and n = 5 (2); X = NCO(-) and n = 4 (3); INH = isoniazid, a drug widely used to treat tuberculosis) derived from the reaction between the copper(II) chloride and isoniazid in the presence or absence of pseudohalide ions (NCS(-) or NCO(-)) were synthesized and characterized by infrared spectrometry, electronic absorption spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, elemental analysis, melting points and complexometry with 2,2',2'',2'''-(Ethane-1,2-diyldinitrilo)tetraacetic acid (EDTA). The characterization techniques allowed us to confirm the formation of the copper(II) complexes. The Cu(II) complexes were loaded into microemulsion (MEs) composed of 10% phase oil (cholesterol), 10% surfactant [soy oleate and Brij® 58 (1:2)] and 80% aqueous phase (phosphate buffer pH = 7.4) prepared by sonication. The Cu(II) complex-loaded MEs displayed sizes ranging from 158.0 ± 1.060 to 212.6 ± 1.539 nm, whereas the polydispersity index (PDI) ranged from 0.218 ± 0.007 to 0.284 ± 0.034. The antibacterial activity of the free compounds and those that were loaded into the MEs against Staphylococcus aureus ATCC® 25923 and Escherichia coli ATCC® 25922, as evaluated by a microdilution technique, and the cytotoxicity index (IC50) against the Vero cell line (ATCC® CCL-81(TM)) were used to calculate the selectivity index (SI). Among the free compounds, only compound 2 (MIC 500 μg/mL) showed activity for S. aureus. After loading the compounds into the MEs, the antibacterial activity of compounds 1, 2 and 3 was significantly increased against E. coli (MIC's 125, 125 and 500 μg/mL, respectively) and S. aureus (MICs 250, 500 and 125 μg/mL, respectively). The loaded compounds were less toxic against the Vero
Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury.

PubMed

Li, Tuoyi; Yu, Bing; Liu, Zhixin; Li, Jingyuan; Ma, Mingliang; Wang, Yingbao; Zhu, Mingjiang; Yin, Huiyong; Wang, Xiaofeng; Fu, Yi; Yu, Fang; Wang, Xian; Fang, Xiaohong; Sun, Jinpeng; Kong, Wei

2018-01-02

Hyperhomocysteinemia (HHcy) is a risk factor for various cardiovascular diseases. However, the mechanism underlying HHcy-aggravated vascular injury remains unclear. Here we show that the aggravation of abdominal aortic aneurysm by HHcy is abolished in mice with genetic deletion of the angiotensin II type 1 (AT1) receptor and in mice treated with an AT1 blocker. We find that homocysteine directly activates AT1 receptor signalling. Homocysteine displaces angiotensin II and limits its binding to AT1 receptor. Bioluminescence resonance energy transfer analysis reveals distinct conformational changes of AT1 receptor upon binding to angiotensin II and homocysteine. Molecular dynamics and site-directed mutagenesis experiments suggest that homocysteine regulates the conformation of the AT1 receptor both orthosterically and allosterically by forming a salt bridge and a disulfide bond with its Arg 167 and Cys 289 residues, respectively. Together, these findings suggest that strategies aimed at blocking the AT1 receptor may mitigate HHcy-associated aneurysmal vascular injuries.
Mediator, TATA-binding protein, and RNA polymerase II contribute to low histone occupancy at active gene promoters in yeast.

PubMed

Ansari, Suraiya A; Paul, Emily; Sommer, Sebastian; Lieleg, Corinna; He, Qiye; Daly, Alexandre Z; Rode, Kara A; Barber, Wesley T; Ellis, Laura C; LaPorta, Erika; Orzechowski, Amanda M; Taylor, Emily; Reeb, Tanner; Wong, Jason; Korber, Philipp; Morse, Randall H

2014-05-23

Transcription by RNA polymerase II (Pol II) in eukaryotes requires the Mediator complex, and often involves chromatin remodeling and histone eviction at active promoters. Here we address the role of Mediator in recruitment of the Swi/Snf chromatin remodeling complex and its role, along with components of the preinitiation complex (PIC), in histone eviction at inducible and constitutively active promoters in the budding yeast Saccharomyces cerevisiae. We show that recruitment of the Swi/Snf chromatin remodeling complex to the induced CHA1 promoter, as well as its association with several constitutively active promoters, depends on the Mediator complex but is independent of Mediator at the induced MET2 and MET6 genes. Although transcriptional activation and histone eviction at CHA1 depends on Swi/Snf, Swi/Snf recruitment is not sufficient for histone eviction at the induced CHA1 promoter. Loss of Swi/Snf activity does not affect histone occupancy of several constitutively active promoters; in contrast, higher histone occupancy is seen at these promoters in Mediator and PIC component mutants. We propose that an initial activator-dependent, nucleosome remodeling step allows PIC components to outcompete histones for occupancy of promoter sequences. We also observe reduced promoter association of Mediator and TATA-binding protein in a Pol II (rpb1-1) mutant, indicating mutually cooperative binding of these components of the transcription machinery and indicating that it is the PIC as a whole whose binding results in stable histone eviction. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Synthesis, characterization and in vitro antimicrobial studies of Co(II), Ni(II) and Cu(II) complexes derived from macrocyclic compartmental ligand

NASA Astrophysics Data System (ADS)

El-Gammal, O. A.; Bekheit, M. M.; El-Brashy, S. A.

2015-02-01

New Co(II), Ni(II) and Cu(II) complexes derived from tetradentate macrocyclic nitrogen ligand, (1E,4E,8E,12E)-5,8,13,16-tetramethyl-1,4,9,12-tetrazacyclohexadeca-4,8,12,16-tetraene (EDHDH) have been synthesized. The complexes have been characterized by elemental analysis, spectral (IR, UV-Vis, 1H NMR and ESR (for Cu(II) complex)) mass, and magnetic as well as thermal analysis measurements. The complexes afforded the formulae: [Cu(EDHDH)Cl2]·2EtOH and [M(EDHDH)X2]·nH2O where M = Co(II) and Ni(II), X = Cl- or OH-, n = 1,0, respectively. The data revealed an octahedral arrangement with N4 tetradentate donor sites in addition to two Cl atoms occupying the other two sites. ESR spectrum of Cu2+ complex confirmed the suggested geometry with values of a α2and β2 indicating that the in-plane σ-bonding and in-plane π-bonding are appreciably covalent, and are consistent with very strong σ-in-plane bonding in the complexes. The molecular modeling is drawn and showed the bond length, bond angle, chemical reactivity, energy components (kcal/mol) and binding energy (kcal/mol) for all the title compounds using DFT method. Also, the thermal behavior and the kinetic parameters of degradation were determined using Coats-Redfern and Horowitz-Metzger methods. Moreover, the in vitro antibacterial studies of all compounds screened against pathogenic bacteria (two Gram +ve and two Gram -ve) to assess their inhibiting potential. The assay indicated that the inhibition potential is metal ion dependent. The ligand, EDHDH, Co(II) and Cu(II) complexes exhibited a remarkable antibacterial activity against Streptococcus Pyogenes as Gram +ve and Proteus vulgaris as Gram -ve bacterial strains. On the other hand, Ni(II) complex revealed a moderate antibacterial activity against both Gram +ve organisms and no activity against Gram -ve bacterial strain.
77 FR 1084 - Agency Information Collection Activities Under Review; Title II of the Americans With...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-09

... DEPARTMENT OF JUSTICE [OMB Number 1190-0009] Agency Information Collection Activities Under Review; Title II of the Americans With Disabilities Act of 1990/Section 504 of the Rehabilitation Act of 1973 Discrimination Complaint Form ACTION: 30-Day Notice of Information Collection under review The Department of Justice, Civil Rights Division,...
Anti-inflammatory drugs interacting with Zn(II), Cd(II) and Pt(II) metal ions.

PubMed

Dendrinou-Samara, C; Tsotsou, G; Ekateriniadou, L V; Kortsaris, A H; Raptopoulou, C P; Terzis, A; Kyriakidis, D A; Kessissoglou, D P

1998-09-01

Complexes of Zn(II), Cd(II) and Pt(II) metal ions with the anti-inflammatory drugs, 1-methyl-5-(p-toluoyl)-1H-pyrrole-2-acetic acid (Tolmetin), alpha-methyl-4-(2-methylpropyl)benzeneacetic acid (Ibuprofen), 6-methoxy-alpha-methylnaphthalene-2-acetic acid (Naproxen) and 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid (indomethacin) have been synthesized and characterized. In the structurally characterized Cd(naproxen)2 complex the anti-inflammatory drugs acts as bidentate chelate ligand coordinatively bound to metal ions through the deprotonated carboxylate group. Crystal data for 1: [C32H26O8Cd], orthorhombic, space group P22(1)2(1), a = 5.693(2) (A), b = 8.760(3) (A), c = 30.74(1) (A), V = 1533(1) A3, Z = 2. Antibacterial and growth inhibitory activity is higher than that of the parent ligands or the platinum(II) diamine compounds.

Differential Light-induced Responses in Sectorial Inherited Retinal Degeneration*

PubMed Central

Ramon, Eva; Cordomí, Arnau; Aguilà, Mònica; Srinivasan, Sundaramoorthy; Dong, Xiaoyun; Moore, Anthony T.; Webster, Andrew R.; Cheetham, Michael E.; Garriga, Pere

2014-01-01

Retinitis pigmentosa (RP) is a group of genetically and clinically heterogeneous inherited degenerative retinopathies caused by abnormalities of photoreceptors or retinal pigment epithelium in the retina leading to progressive sight loss. Rhodopsin is the prototypical G-protein-coupled receptor located in the vertebrate retina and is responsible for dim light vision. Here, novel M39R and N55K variants were identified as causing an intriguing sector phenotype of RP in affected patients, with selective degeneration in the inferior retina. To gain insights into the molecular aspects associated with this sector RP phenotype, whose molecular mechanism remains elusive, the mutations were constructed by site-directed mutagenesis, expressed in heterologous systems, and studied by biochemical, spectroscopic, and functional assays. M39R and N55K opsins had variable degrees of chromophore regeneration when compared with WT opsin but showed no gross structural misfolding or altered trafficking. M39R showed a faster rate for transducin activation than WT rhodopsin with a faster metarhodopsinII decay, whereas N55K presented a reduced activation rate and an altered photobleaching pattern. N55K also showed an altered retinal release from the opsin binding pocket upon light exposure, affecting its optimal functional response. Our data suggest that these sector RP mutations cause different protein phenotypes that may be related to their different clinical progression. Overall, these findings illuminate the molecular mechanisms of sector RP associated with rhodopsin mutations. PMID:25359768
Blood Program in World War II. Medical Department, United States Army

DTIC Science & Technology

1964-01-01

Branch Lieutenant Colonel JEROME RUDBERG, MSC, USA, Chief, Information Activities Branch RODERICK M. ENGERT, Chief, General Reference and Research... Activities of Medical Consultants Vol. II. Infectious Diseases Preventive Medicine in World War II: Vol. II. Environmental Hygiene Vol. III. Personal...Other Than Malaria Vr VIII Surgery in World War II: Activities of Surgical Consultants, vol. I Activities of Surgical Consultants, vol. II General
Discovery of Type II Inhibitors of TGFβ-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2)

PubMed Central

2015-01-01

We developed a pharmacophore model for type II inhibitors that was used to guide the construction of a library of kinase inhibitors. Kinome-wide selectivity profiling of the library resulted in the identification of a series of 4-substituted 1H-pyrrolo[2,3-b]pyridines that exhibited potent inhibitory activity against two mitogen-activated protein kinases (MAPKs), TAK1 (MAP3K7) and MAP4K2, as well as pharmacologically well interrogated kinases such as p38α (MAPK14) and ABL. Further investigation of the structure–activity relationship (SAR) resulted in the identification of potent dual TAK1 and MAP4K2 inhibitors such as 1 (NG25) and 2 as well as MAP4K2 selective inhibitors such as 16 and 17. Some of these inhibitors possess good pharmacokinetic properties that will enable their use in pharmacological studies in vivo. A 2.4 Å cocrystal structure of TAK1 in complex with 1 confirms that the activation loop of TAK1 assumes the DFG-out conformation characteristic of type II inhibitors. PMID:25075558
Anti-Leishmania activity of new ruthenium(II) complexes: Effect on parasite-host interaction.

PubMed

Costa, Mônica S; Gonçalves, Yasmim G; Nunes, Débora C O; Napolitano, Danielle R; Maia, Pedro I S; Rodrigues, Renata S; Rodrigues, Veridiana M; Von Poelhsitz, Gustavo; Yoneyama, Kelly A G

2017-10-01

Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania. The many complications presented by the current treatment - including high toxicity, high cost and parasite resistance - make the development of new therapeutic agents indispensable. The present study aims to evaluate the anti-Leishmania potential of new ruthenium(II) complexes, cis‑[Ru II (η 2 -O 2 CR)(dppm) 2 ]PF 6 , with dppm=bis(diphenylphosphino)methane and R=4-butylbenzoate (bbato) 1, 4-(methylthio)benzoate (mtbato) 2 and 3-hydroxy-4-methoxybenzoate (hmxbato) 3, in promastigote cytotoxicity and their effect on parasite-host interaction. The cytotoxicity of complexes was analyzed by MTT assay against Leishmania (Leishmania) amazonensis, Leishmania (Viannia) braziliensis, Leishmania (Leishmania) infantum promastigotes and the murine macrophage (RAW 264.7). The effect of complexes on parasite-host interaction was evaluated by in vitro infectivity assay performed in the presence of two different concentrations of each complex: the promastigote IC 50 value and the concentration nontoxic to 90% of RAW 264.7 macrophages. Complexes 1-3 exhibited potent cytotoxic activity against all Leishmania species assayed. The IC 50 values ranged from 7.52-12.59μM (complex 1); 0.70-3.28μM (complex 2) and 0.52-1.75μM (complex 3). All complexes significantly inhibited the infectivity index at both tested concentrations. The infectivity inhibitions ranged from 37 to 85%. Interestingly, the infectivity inhibitions due to complex action did not differ significantly at either of the tested concentrations, except for the complex 1 against Leishmania (Leishmania) infantum. The infectivity inhibitions resulted from reductions in both percentage of infected macrophages and number of parasites per macrophage. Taken together the results suggest remarkable leishmanicidal activity in vitro by these new ruthenium(II) complexes. Copyright © 2017 Elsevier Inc. All rights reserved.
Brain-mediated dysregulation of the bone marrow activity in angiotensin II-induced hypertension.

PubMed

Jun, Joo Yun; Zubcevic, Jasenka; Qi, Yanfei; Afzal, Aqeela; Carvajal, Jessica Marulanda; Thinschmidt, Jeffrey S; Grant, Maria B; Mocco, J; Raizada, Mohan K

2012-11-01

Oxidative stress in the brain is implicated in increased sympathetic drive, inflammatory status, and vascular dysfunctions, associated with development and establishment of hypertension. However, little is known about the mechanism of this impaired brain-vascular communication. Here, we tested the hypothesis that increased oxidative stress in the brain cardioregulatory areas, such as the paraventricular nucleus of the hypothalamus, is driven by mitochondrial reactive oxygen species and leads to increased inflammatory cells (ICs) and decreased/dysfunctional endothelial progenitor cells (EPCs), thereby compromising vasculature repair and accelerating hypertension. Chronic angiotensin II infusion resulted in elevated blood pressure and sympathetic vasomotor drive, decreased spontaneous baroreflex gain, and increased microglia activation in the paraventricular nucleus. This was associated with 46% decrease in bone marrow (BM)-derived EPCs and 250% increase in BM ICs, resulting in 5-fold decrease of EPC/IC ratio in the BM. Treatment with mitochondrial-targeted antioxidant, a scavenger of mitochondrial O(2)(-·), intracerebroventricularly but not subcutaneously attenuated angiotensin II-induced hypertension, decreased activation of microglia in the paraventricular nucleus, and normalized EPCs/ICs. This functional communication between the brain and BM was confirmed by retrograde neuronal labeling from the BM with green fluorescent protein-tagged pseudorabies virus. Administration of green fluorescent protein-tagged pseudorabies virus into the BM resulted in predominant labeling of paraventricular nucleus neurons within 3 days, with some fluorescence in the nucleus tractus solitarius, the rostral ventrolateral medulla, and subfornical organ. Taken together, these data demonstrate that inhibition of mitochondrial reactive oxygen species attenuates angiotensin II-induced hypertension and corrects the imbalance in EPCs/ICs in the BM. They suggest that an imbalance in
The synthesis of corncobs (zea mays) active charcoal and water hyacinth (eichornia crassipes) adsorbent to adsorb Pb(II) with it’s analysis using solid-phase spectrophotometry (sps)

NASA Astrophysics Data System (ADS)

Saputro, S.; Masykuri, M.; Mahardiani, L.; Kurniastuti, D.

2018-03-01

This research aim to examine the effect of the combination between corncobs and water hyacinth to adsorb lead (II), the most effective combination have determined by compared the ratio of corncobs adsorbent and water hyacinth to the increasing adsorption of the Pb(II), prove the effectiveness of the solid-phase spectrophotometry (sps) to determine the levels of Pb(II) as the result of the corncobs active charcoal adsorption and water hyacinth in the level of µg/L. The research method used is experimental method. The data collecting technique is carried out by several stages, which are carbonization using muffle furnace at a temperature of 350°C for 1.5 hours, activation of the corncobs charcoal and water hyacinth using HCl 1M and HCl 5M activator, contacting the adsorbent of corncobs active charcoal and water hyacinth with liquid waste simulation of Pb(II) using variation of corncobns and water hyacinth, 1:0; 0:1; 1:1; 2:1; 1:2, analysis of Pb(II) using an sps, characterization of corncobs active charcoal adsorbent and water hyacinth using FTIR. Research results show that the combined effect of activated charcoal corncobs and water hyacinth can increase the ability of the adsorbent to absorb Pb(II), the optimum adsorbent mass ratio of 1:1 with the absorption level of 90.33%, SPS is an effective method to analyze the decreasing level of Pb(II) as the adsorbtion result of the corncobs active charcoal and water hyacinth in the level of µg/L, with the limit of detection (LOD) of 0.06 µg/L.
Evaluation of adsorption properties of sulphurised activated carbon for the effective and economically viable removal of Zn(II) from aqueous solutions.

PubMed

Anoop Krishnan, K; Sreejalekshmi, K G; Vimexen, V; Dev, Vinu V

2016-02-01

The prospective application of sulphurised activated carbon (SAC) as an ecofriendly and cost-effective adsorbent for Zinc(II) removal from aqueous phase is evaluated, with an emphasis on kinetic and isotherm aspects. SAC was prepared from sugarcane bagasse pith obtained from local juice shops in Sree Bhadrakali Devi Temple located at Ooruttukala, Neyyattinkara, Trivandrum, India during annual festive seasons. Activated carbon modified with sulphur containing ligands was opted as the adsorbent to leverage on the affinity of Zn(II) for sulphur. We report batch-adsorption experiments for parameter optimisations aiming at maximum removal of Zn(II) from liquid-phase using SAC. Adsorption of Zn(II) onto SAC was maximum at pH 6.5. For initial concentrations of 25 and 100mgL(-1), maximum of 12.3mgg(-1) (98.2%) and 23.7mgg(-1) (94.8%) of Zn(II) was adsorbed onto SAC at pH 6.5. Kinetic and equilibrium data were best described by pseudo-second-order and Langmuir models, respectively. A maximum adsorption capacity of 147mgg(-1) was obtained for the adsorption of Zn(II) onto SAC from aqueous solutions. The reusability of the spent adsorbent was also determined. Copyright © 2015 Elsevier Inc. All rights reserved.
Structures of the Mycobacterium tuberculosis GlpX protein (class II fructose-1,6-bisphosphatase): implications for the active oligomeric state, catalytic mechanism and citrate inhibition

DOE PAGES

Wolf, Nina M.; Gutka, Hiten J.; Movahedzadeh, Farahnaz; ...

2018-04-03

The crystal structures of native class II fructose-1,6-bisphosphatase (FBPaseII) from Mycobacterium tuberculosis at 2.6 Å resolution and two active-site protein variants are presented. The variants were complexed with the reaction product fructose 6-phosphate (F6P). The Thr84Ala mutant is inactive, while the Thr84Ser mutant has a lower catalytic activity. The structures reveal the presence of a 222 tetramer, similar to those described for fructose-1,6/sedoheptulose-1,7-bisphosphatase from Synechocystis (strain 6803) as well as the equivalent enzyme from Thermosynechococcus elongatus . This homotetramer corresponds to a homologous oligomer that is present but not described in the crystal structure of FBPaseII from Escherichia coli and ismore » probably conserved in all FBPaseIIs. The constellation of amino-acid residues in the active site of FBPaseII from M. tuberculosis ( Mt FBPaseII) is conserved and is analogous to that described previously for the E. coli enzyme. Moreover, the structure of the active site of the partially active (Thr84Ser) variant and the analysis of the kinetics are consistent with the previously proposed catalytic mechanism. The presence of metabolites in the crystallization medium (for example citrate and malonate) and in the corresponding crystal structures of Mt FBPaseII, combined with their observed inhibitory effect, could suggest the existence of an uncharacterized inhibition of this class of enzymes besides the allosteric inhibition by adenosine monophosphate observed for the Synechocystis enzyme. The structural and functional insights derived from the structure of Mt FBPaseII will provide critical information for the design of lead inhibitors, which will be used to validate this target for future chemical intervention.« less
Structures of the Mycobacterium tuberculosis GlpX protein (class II fructose-1,6-bisphosphatase): implications for the active oligomeric state, catalytic mechanism and citrate inhibition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolf, Nina M.; Gutka, Hiten J.; Movahedzadeh, Farahnaz

The crystal structures of native class II fructose-1,6-bisphosphatase (FBPaseII) from Mycobacterium tuberculosis at 2.6 Å resolution and two active-site protein variants are presented. The variants were complexed with the reaction product fructose 6-phosphate (F6P). The Thr84Ala mutant is inactive, while the Thr84Ser mutant has a lower catalytic activity. The structures reveal the presence of a 222 tetramer, similar to those described for fructose-1,6/sedoheptulose-1,7-bisphosphatase from Synechocystis (strain 6803) as well as the equivalent enzyme from Thermosynechococcus elongatus . This homotetramer corresponds to a homologous oligomer that is present but not described in the crystal structure of FBPaseII from Escherichia coli and ismore » probably conserved in all FBPaseIIs. The constellation of amino-acid residues in the active site of FBPaseII from M. tuberculosis ( Mt FBPaseII) is conserved and is analogous to that described previously for the E. coli enzyme. Moreover, the structure of the active site of the partially active (Thr84Ser) variant and the analysis of the kinetics are consistent with the previously proposed catalytic mechanism. The presence of metabolites in the crystallization medium (for example citrate and malonate) and in the corresponding crystal structures of Mt FBPaseII, combined with their observed inhibitory effect, could suggest the existence of an uncharacterized inhibition of this class of enzymes besides the allosteric inhibition by adenosine monophosphate observed for the Synechocystis enzyme. The structural and functional insights derived from the structure of Mt FBPaseII will provide critical information for the design of lead inhibitors, which will be used to validate this target for future chemical intervention.« less
Synthesis, characterization, antibacterial activity, SOD mimic and interaction with DNA of drug based copper(II) complexes

NASA Astrophysics Data System (ADS)

Patel, Mohan N.; Dosi, Promise A.; Bhatt, Bhupesh S.; Thakkar, Vasudev R.

2011-02-01

Novel metal complexes of the second-generation quinolone antibacterial agent enrofloxacin with copper(II) and neutral bidentate ligands have been prepared and characterized with elemental analysis reflectance, IR and mass spectroscopy. Complexes have been screened for their in-vitro antibacterial activity against two Gram (+ve)Staphylococcus aureus, Bacillus subtilis, and three Gram (-ve)Serratia marcescens, Escherichia coli and Pseudomonas aeruginosa organisms using the double dilution technique. The binding of this complex with CT-DNA has been investigated by absorption titration, salt effect and viscosity measurements. Binding constant is ranging from 1.3 × 10 4-3.7 × 10 4. The cleavage ability of complexes has been assessed by gel electrophoresis using pUC19 DNA. The catalytic activity of the copper(II) complexes towards the superoxide anion (O 2rad -) dismutation was assayed by their ability to inhibit the reduction of nitroblue tetrazolium (NBT).
Enhanced angiotensin-converting enzyme activity and systemic reactivity to angiotensin II in normotensive rats exposed to a high-sodium diet

PubMed Central

Crestani, Sandra; Júnior, Arquimedes Gasparotto; Marques, Maria C.A.; Sullivan, Jennifer C.; Webb, R. Clinton; da Silva-Santos, J. Eduardo

2016-01-01

A high salt diet is associated with reduced activity of the renin–angiotensin–aldosterone system (RAAS). However, normotensive rats exposed to high sodium do not show changes in systemic arterial pressure. We hypothesized that, despite the reduced circulating amounts of angiotensin II induced by a high salt diet, the cardiovascular system’s reactivity to angiotensin II is increased in vivo, contributing to maintain arterial pressure at normal levels. Male Wistar rats received chow containing 0.27% (control), 2%, 4%, or 8% NaCl for six weeks. The high-sodium diet did not lead to changes in arterial pressure, although plasma levels of angiotensin II and aldosterone were reduced in the 4% and 8% NaCl groups. The 4% and 8% NaCl groups showed enhanced pressor responses to angiotensin I and II, accompanied by unchanged and increased angiotensin-converting enzyme activity, respectively. The 4% NaCl group showed increased expression of angiotensin II type 1 receptors and reduced expression of angiotensin II type 2 receptors in the aorta. In addition, the hypotensive effect of losartan was reduced in both 4% and 8% NaCl groups. In conclusion these results explain, at least in part, why the systemic arterial pressure is maintained at normal levels in non-salt sensitive and healthy rats exposed to a high salt diet, when the functionality of RAAS appears to be blunted, as well as suggest that angiotensin II has a crucial role in the vascular dysfunction associated with high salt intake, even in the absence of hypertension. PMID:24321189
Rho/Rho-dependent kinase affects locomotion and actin-myosin II activity of Amoeba proteus.

PubMed

Kłopocka, W; Redowicz, M J

2004-10-01

The highly motile free-living unicellular organism Amoeba proteus has been widely used as a model to study cell motility. However, the molecular mechanisms underlying its unique locomotion are still scarcely known. Recently, we have shown that blocking the amoebae's endogenous Rac- and Rho-like proteins led to distinct and irreversible changes in the appearance of these large migrating cells as well as to a significant inhibition of their locomotion. In order to elucidate the mechanism of the Rho pathway, we tested the effects of blocking the endogenous Rho-dependent kinase (ROCK) by anti-ROCK antibodies and Y-27632, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride, a specific inhibitor of ROCK, on migrating amoebae and the effect of the Rho and ROCK inhibition on the actin-activated Mg-ATPase of the cytosolic fraction of the amoebae. Amoebae microinjected with anti-ROCK inhibitors remained contracted and strongly attached to the glass surface and exhibited an atypical locomotion. Despite protruding many pseudopodia that were advancing in various directions, the amoebae could not effectively move. Immunofluorescence studies showed that ROCK-like protein was dispersed throughout the cytoplasm and was also found in the regions of actin-myosin II interaction during both isotonic and isometric contraction. The Mg-ATPase activity was about two- to threefold enhanced, indicating that blocking the Rho/Rho-dependent kinase activated myosin. It is possible then that in contrast to the vertebrate cells, the inactivation of Rho/Rho-dependent kinase in amoebae leads to the activation of myosin II and to the observed hypercontracted cells which cannot exert effective locomotion.
Redox cycling of Cu(II) by 6-mercaptopurine leads to ROS generation and DNA breakage: possible mechanism of anticancer activity.

PubMed

Rehman, Sayeed Ur; Zubair, Haseeb; Sarwar, Tarique; Husain, Mohammed Amir; Ishqi, Hassan Mubarak; Nehar, Shamshun; Tabish, Mohammad

2015-02-01

6-Mercaptopurine (6MP) is a well-known purine antimetabolite used to treat childhood acute lymphoblastic leukemia and other diseases. Cancer cells as compared to normal cells are under increased oxidative stress and show high copper level. These differences between cancer cells and normal cells can be targeted to develop effective cancer therapy. Pro-oxidant property of 6MP in the presence of metal ions is not well documented. Redox cycling of Cu(II) to Cu(I) was found to be efficiently mediated by 6MP. We have performed a series of in vitro experiments to demonstrate the pro-oxidant property of 6MP in the presence of Cu(II). Studies on human lymphocytes confirmed the DNA damaging ability of 6MP in the presence of Cu(II). Since 6MP possesses DNA damaging ability by producing reactive oxygen species (ROS) in the presence of Cu(II), it may also possess apoptosis-inducing activity by involving endogenous copper ions. Essentially, this would be an alternative and copper-dependent pathway for anticancer activity of 6MP.
Synthesis and Characterization of New Palladium(II) Thiosemicarbazone Complexes and Their Cytotoxic Activity against Various Human Tumor Cell Lines

PubMed Central

Hernández, Wilfredo; Paz, Juan; Carrasco, Fernando; Spodine, Evgenia; Manzur, Jorge; Sieler, Joachim; Blaurock, Steffen; Beyer, Lothar

2013-01-01

The palladium(II) bis-chelate complexes of the type [Pd(TSC1-5)2] (6–10), with their corresponding ligands 4-phenyl-1-(acetone)-thiosemicarbazone, HTSC1 (1), 4-phenyl-1-(2′-chloro-benzaldehyde)-thiosemicarbazone, HTSC2 (2), 4-phenyl-1-(3′-hydroxy-benzaldehyde)-thiosemicarbazone, HTSC3 (3), 4-phenyl-1-(2′-naphthaldehyde)-thiosemicarbazone, HTSC4 (4), and 4-phenyl-1-(1′-nitro-2′-naphthaldehyde)-thiosemicarbazone, HTSC5 (5), were synthesized and characterized by elemental analysis and spectroscopic techniques (IR and 1H- and 13C-NMR). The molecular structure of HTSC3, HTSC4, and [Pd(TSC1)2] (6) have been determined by single crystal X-ray crystallography. Complex 6 shows a square planar geometry with two deprotonated ligands coordinated to PdII through the azomethine nitrogen and thione sulfur atoms in a cis arrangement. The in vitro cytotoxic activity measurements indicate that the palladium(II) complexes (IC50 = 0.01–9.87 μM) exhibited higher antiproliferative activity than their free ligands (IC50 = 23.48–70.86 and >250 μM) against different types of human tumor cell lines. Among all the studied palladium(II) complexes, the [Pd(TSC3)2] (8) complex exhibited high antitumor activity on the DU145 prostate carcinoma and K562 chronic myelogenous leukemia cells, with low values of the inhibitory concentration (0.01 and 0.02 μM, resp.). PMID:24391528
Synthesis, characterization, antimicrobial activity and DFT studies of 2-(pyrimidin-2-ylamino)naphthalene-1,4-dione and its Mn(II), Co(II), Ni(II) and Zn(II) complexes

NASA Astrophysics Data System (ADS)

Chioma, Festus; Ekennia, Anthony C.; Ibeji, Collins U.; Okafor, Sunday N.; Onwudiwe, Damian C.; Osowole, Aderoju A.; Ujam, Oguejiofo T.

2018-07-01

A pyrimidine-based ligand, 2-(pyrimidin-2-ylamino)naphthalene-1,4-dione (L), has been synthesized by the reaction of 2-aminopyrimidine with 2-hydroxy-1,4-napthoquinone. Reaction of the ligand with Ni(II), Co(II), Mn(II) and Zn(II) acetate gave the corresponding metal complexes which were characterized by spectroscopic techniques, (infrared, electronic), elemental analysis, room-temperature magnetometry, conductance measurements and thermogravimetry-differential scanning calorimetry (TG-DSC) analyses. The room-temperature magnetic data and electronic spectral measurements of the complexes gave evidence of 4-coordinate square planar/tetrahedral geometry. The thermal analyses values obtained indicated the monohydrate complexes. The antimicrobial screening of the compounds showed mild to very good results. The Mn(II) complex showed the best result within in the range of 11.5-29 mm. The electronic, structural and spectroscopic properties of the complexes were further discussed using density functional theory. Molecular docking studies showed significant binding affinity with the drug targets and the metal complexes have potentials to be used as drugs.
Extreme optical Fe II emission in luminous IRAS active galactic nuclei

NASA Technical Reports Server (NTRS)

Lipari, Sebastian; Terlevich, Roberto; Macchetto, F.

1993-01-01

Results of a program of studies and observations of strong optical Fe II emission in luminous and ultraluminous IRAS AGN are presented. New spectroscopic observations and studies of three known ultraluminous IRAS AGN with extreme optical Fe II emission, the discovery that PHL 1092 is a new ultraluminous IRAS AGN, and the detection of two new AGN with strongly variable flux in the optical Fe II emission lines are reported. These results are used to test the correlations between the Fe II emission and properties at other wavelengths such as the L(IR) and the radio emission. IR AGN with extreme Fe II emission are found to belong to a very important group of AGN, whose properties provide insight into the origin of the extreme Fe II emission and into the relation between the starburst and AGN phenomena.
Selecting promising treatments in randomized Phase II cancer trials with an active control.

PubMed

Cheung, Ying Kuen

2009-01-01

The primary objective of Phase II cancer trials is to evaluate the potential efficacy of a new regimen in terms of its antitumor activity in a given type of cancer. Due to advances in oncology therapeutics and heterogeneity in the patient population, such evaluation can be interpreted objectively only in the presence of a prospective control group of an active standard treatment. This paper deals with the design problem of Phase II selection trials in which several experimental regimens are compared to an active control, with an objective to identify an experimental arm that is more effective than the control or to declare futility if no such treatment exists. Conducting a multi-arm randomized selection trial is a useful strategy to prioritize experimental treatments for further testing when many candidates are available, but the sample size required in such a trial with an active control could raise feasibility concerns. In this study, we extend the sequential probability ratio test for normal observations to the multi-arm selection setting. The proposed methods, allowing frequent interim monitoring, offer high likelihood of early trial termination, and as such enhance enrollment feasibility. The termination and selection criteria have closed form solutions and are easy to compute with respect to any given set of error constraints. The proposed methods are applied to design a selection trial in which combinations of sorafenib and erlotinib are compared to a control group in patients with non-small-cell lung cancer using a continuous endpoint of change in tumor size. The operating characteristics of the proposed methods are compared to that of a single-stage design via simulations: The sample size requirement is reduced substantially and is feasible at an early stage of drug development.
DNA Cleavage, Cytotoxic Activities, and Antimicrobial Studies of Ternary Copper(II) Complexes of Isoxazole Schiff Base and Heterocyclic Compounds

PubMed Central

Chityala, Vijay Kumar; Sathish Kumar, K.; Macha, Ramesh; Tigulla, Parthasarathy; Shivaraj

2014-01-01

Novel mixed ligand bivalent copper complexes [Cu. L. A. ClO 4] and [Cu. L. A] where “L” is Schiff bases, namely 2-((3,4-dimethylisoxazol-5-ylimino)methyl)-4-bromophenol (DMIIMBP)/2-((3,4-dimethylisoxazol-5-ylimino)methyl)-4-chlorophenol (DMIIMCP), and “A” is heterocyclic compound, such as 1,10-phenanthroline (phen)/2,21-bipyridyl (bipy)/8-hydroxyquinoline (oxine)/5-chloro-8-hydroxyquinoline (5-Cl-oxine), have been synthesized. These complexes have been characterized by IR, UV-Vis, ESR, elemental analysis, magnetic moments, TG, and DTA. On the basis of spectral studies and analytical data, five-coordinated square pyramidal/four-coordinated square planar geometry is assigned to all complexes. The ligands and their ternary complexes with Cu(II) have been screened for antimicrobial activity against bacteria and fungi by paper disc method. The antimicrobial studies of Schiff bases and their metal complexes showed significant activity and further it is observed that the metal complexes showed more activity than corresponding Schiff bases. In vitro antitumor activity of Cu(II) complexes was assayed against human cervical carcinoma (HeLa) cancer cells and it was observed that few complexes exhibit good antitumor activity on HeLa cell lines. The DNA cleavage studies have also been carried out on pBR 322 and it is observed that these Cu(II) complexes are capable of cleaving supercoiled plasmid DNA in the presence of H2O2 and UV light. PMID:24895493
Interaction with biomacromolecules and antiproliferative activities of Mn(II), Ni(II), Zn(II) complexes of demethylcantharate and 2,2'-bipyridine

NASA Astrophysics Data System (ADS)

Zhang, Fan; Lin, Qiu-Yue; Hu, Wan-Li; Song, Wen-Ji; Shen, Shu-Ting; Gui, Pan

2013-06-01

Three new transition metal complexes [Mn2(DCA)2(bipy)2]·5H2O (1), [M2(DCA)2(bipy)2(H2O)]·10H2O(M = Ni(II)(2);Zn(II)(3)), (DCA = demethylcantharate, 7-oxabicyclo[2,2,1]heptane-2,3-dicarboxylate, C8H8O5) were synthesized and characterized by elemental analysis, molar conductance, infrared spectra and X-ray diffraction techniques. Each metal ion was six-coordinated in complexes. Complex 1 has a Mn2O2 center. Complexes 2 and 3 have asymmetric binuclear structure. Great amount of intermolecular hydrogen-bonding and π-π* stacking interactions were formed in these complex structures. The DNA-binding properties of complexes were investigated by electronic absorption spectra and viscosity measurements. The DNA binding constants Kb/(L mol-1) were 1.71 × 104 (1), 2.62 × 104 (2) and 1.59 × 104 (3) at 298 K. The complexes could quench the intrinsic fluorescence of bovine serum albumin (BSA) strongly through static quenching. The protein binding constants Ka/(L mol-1) were 7.27 × 104 (1), 4.55 × 104 (2) and 7.87 × 104 L mol-1 (3) and binding site was one. The complexes bind more tightly with DNA and BSA than with ligands. Complexes 1 and 3 had stronger inhibition ratios than Na2(DCA) against human hepatoma cells (SMMC-7721) lines and human gastric cancer cells (MGC80-3) lines in vitro. Complex 3 showed the strongest antiproliferative activity against SMMC-7721 (IC50 = 29.46 ± 2.12 μmol L-1) and MGC80-3 (IC50 = 27.02 ± 2.38 μmol L-1), which shows potential in anti-cancer drug development.
Synthesis, characterization, nucleic acid interactions and photoluminescent properties of methaniminium hydrazone Schiff base and its Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes

NASA Astrophysics Data System (ADS)

Sennappan, M.; Murali Krishna, P.; Hosamani, Amar A.; Hari Krishna, R.

2018-07-01

An environmental benign and efficient reaction was carried out via amine exchange and condensation reaction in water and methanol mixture (3:1) and absence of catalyst between 1-[3-(2-hydroxy benzylidene)amine)phenyl]ethanone and benzhydrazide yields methaniminium hydrazone Schiff base in high yield. The prepared ligand was structurally characterized by using single crystal XRD, elemental analysis and spectroscopy (UV-Vis, FT-IR, LC-MS and NMR) techniques. The crystal data indicates the ligand crystallizes in orthorhombic system with Pna21 space group. Further, the ligand was used in synthesis of mononuclear Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes and were characterized by elemental analysis, magnetic moment and spectroscopy (UV-Vis, FT-IR and ESR) studies. The spectral data showed that ligand is coordinated to the metal ion through azomethine nitrogen and methaniminium nitrogen. The DNA binding absorption titrations reveals that, ligand, L and its metal complexes, 1-6 are avid binders to CT- DNA. The apparent binding constant values of compounds are in the order of 106 M-1. The nuclease activity of ligand, L and its metal complexes, 1-6 were investigated by gel electrophoresis method using pUC18 DNA. The photoluminescent properties of the methaniminium hydrazone ligand, L and its various metal complexes, 1-6 were investigated. The emission spectra of both ligand (L) and metal complexes (1-6) exhibits emission in the range of blue to red.

Synthesis, crystal structure and anticancer activity of tetrakis(N-isopropylimidazolidine-2-selenone)platinum(II) chloride

NASA Astrophysics Data System (ADS)

Ahmad, Saeed; Altoum, Ali Osman S.; Vančo, Ján; Křikavová, Radka; Trávníček, Zdeněk; Dvořák, Zdeněk; Altaf, Muhammad; Sohail, Manzar; Isab, Anvarhusein A.

2018-01-01

A Platinum(II) complex of N-isopropylimidazolidine-2-selenone (i-PrImSe), [Pt(i-PrImSe)4]Cl2 (1) was prepared and characterized by elemental analysis, IR and NMR (1H, 13C, 77Se &195Pt) spectroscopy, and X-ray crystallography. The structure of 1 consists of [Pt(i-PrImSe)4]2+ complex ion and chloride counter ions. The platinum(II) atom adopts a distorted square planar geometry. The in vitro antitumor activity of 1 as well as cisplatin, was evaluated by MTT assay against human; ovarian carcinoma A2780 and its cisplatin-resistant subline A2780R, prostate cancer 22Rv1 and breast cancer MCF-7 cell lines. The title complex displayed the activity against the A2780 cells (IC50 = 30.8 μM) at the level comparable to cisplatin (IC50 = 26.8 μM). The interaction studies with sulfur-containing biomolecules revealed its ability to form a variety of intermediates and oxidized species with L-cysteine and reduced glutathione.
Ear-like poly (acrylic acid)-activated carbon nanocomposite: A highly efficient adsorbent for removal of Cd(II) from aqueous solutions.

PubMed

Ge, Huacai; Wang, Jincui

2017-02-01

Poly (acrylic acid) modified activated carbon nanocomposite (PAA-AC) was synthesized. The structure and morphology of this nanocomposite were characterized by FTIR, SEM, TEM, XRD and Zeta potential. The adsorption of some heavy metal ions on PAA-AC was studied. The characterization results indicated that PAA-AC was a novel and ear-like nanosheet material with the thickness of about 40 nm and the diameter of about 300 nm. The adsorption results exhibited that the introduction of carboxyl groups into activated carbon evidently increased the uptake for heavy metal ions and the nanocomposite had maximum uptake for Cd(II). Various variables affecting adsorption of PAA-AC for Cd(II) were systematically explored. The maximum capacity and equilibrium time for adsorption of Cd(II) by PAA-AC were 473.2 mg g -1 and 15 min. Moreover, the removal of Cd(II) for real electroplating wastewater by PAA-AC could reach 98.5%. These meant that the removal of Cd(II) by PAA-AC was highly efficient and fast. The sorption kinetics and isotherm fitted well with the pseudo-second-order model and Langmuir model, respectively. The adsorption mainly was a chemical process by chelation. Thermodynamic studies revealed that the adsorption was a spontaneous and endothermic process. The results revealed that PAA-AC could be considered as a potential candidate for Cd(II) removal. Copyright © 2016 Elsevier Ltd. All rights reserved.
Synthesis, crystal structures and antitumor activities of copper(II) complexes with a 2-acetylpyrazine isonicotinoyl hydrazone ligand

NASA Astrophysics Data System (ADS)

Xu, Jun; Zhou, Tao; Xu, Zhou-Qing; Gu, Xin-Nan; Wu, Wei-Na; Chen, Hong; Wang, Yuan; Jia, Lei; Zhu, Tao-Feng; Chen, Ru-Hua

2017-01-01

Five complexes, [Cu(L)2]·4.5H2O (1), [Cu(HL)2](NO3)2·CH3OH (2) {[Cu2(L)2(NO3)(H2O)2]·(NO3)}n (3), [Cu2(HL)2(SO4)2]·2CH3OH (4) and [Cu4(L)4Cl4]·5H2O (5) based on HL (where HL = 2-acetylpyrazine isonicotinoyl hydrazone) have been synthesized and characterized by X-ray diffraction analyses. The counter anion and organic base during the synthesis procedure influence the structures of the complexes efficiently, which generate five complexes as mono-, bi-, tetra-nuclear and one-dimensional structures. The antitumor activities of the complexes 1-5 (except for complex 3 with the poor solubility) against the Patu8988 human pancreatic cancer, ECA109 human esophagus cancer and SGC7901 human gastric cancer cell lines are screened by MTT assay. The results indicate that the chelation of Cu(II) with the ligand is responsible for the observed high cytotoxicity of the copper(II) complexes and the 1:2 copper species 1 and 2 demonstrate lower antitumor activities than that of the 1:1 copper species 4 and 5. In addition, the in vitro apoptosis inducing activity of the copper(II) complex 5 against SGC7901 cell line is determined. And the results show that the complex can bring about apoptosis of the cancerous cells in vitro.
Nickel(II) Inhibits Tet-Mediated 5-Methylcytosine Oxidation by High Affinity Displacement of the Cofactor Iron(II).

PubMed

Yin, Ruichuan; Mo, Jiezhen; Dai, Jiayin; Wang, Hailin

2017-06-16

Ten-eleven translocation (Tet) family proteins are Fe(II)- and 2-oxoglutarate-dependent dioxygenases that regulate the dynamics of DNA methylation by catalyzing the oxidation of DNA 5-methylcytosine (5mC). To exert physiologically important functions, redox-active iron chelated in the catalytic center of Tet proteins directly involves the oxidation of the multiple substrates. To understand the function and interaction network of Tet dioxygenases, it is interesting to obtain high affinity and a specific inhibitor. Surprisingly, here we found that natural Ni(II) ion can bind to the Fe(II)-chelating motif (HXD) with an affinity of 7.5-fold as high as Fe(II). Consistently, we further found that Ni(II) ion can displace the cofactor Fe(II) of Tet dioxygenases and inhibit Tet-mediated 5mC oxidation activity with an estimated IC 50 of 1.2 μM. Essentially, Ni(II) can be used as a high affinity and selective inhibitor to explore the function and dynamics of Tet proteins.
Combination of rice husk and coconut shell activated adsorbent to adsorb Pb(II) ionic metal and it’s analysis using solid-phase spectrophotometry (sps)

NASA Astrophysics Data System (ADS)

Rohmah, D. N.; Saputro, S.; Masykuri, M.; Mahardiani, L.

2018-03-01

The purpose of this research was to know the effect and determine the mass comparation which most effective combination between rice husk and coconut shell activated adsorbent to adsorb Pb (II) ion using SPS method. This research used experimental method. Technique to collecting this datas of this research is carried out by several stages, which are: (1) carbonization of rice husk and coconut shell adsorbent using muffle furnace at a temperature of 350°C for an hour; (2) activation of the rice husk and coconut shell adsorbent using NaOH 1N and ZnCl2 15% activator; (3) contacting the adsorbent of rice husk and coconut shell activated adsorbent with liquid waste simulation of Pb(II) using variation comparison of rice husk and coconut shell, 1:0; 0:1; 1:1; 2:1; 1:2; (4) analysis of Pb(II) using Solid-Phase Spectrophotometry (SPS); (5) characterization of combination rice husk and coconut shell activated adsorbent using FTIR. The result of this research show that the combined effect of combination rice husk and coconut shell activated adsorbent can increase the ability of the adsorbent to absorb Pb(II) ion then the optimum adsorbent mass ratio required for absorbing 20 mL of Pb(II) ion with a concentration of 49.99 µg/L is a ratio of 2:1 with the absorption level of 97,06%Solid-Phase Spectrophotometry (SPS) is an effective method in the level of µg/L, be marked with the Limit of Detection (LOD) of 0.03 µg/L.
STAR FORMATION ACTIVITY IN THE GALACTIC H II COMPLEX S255-S257

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ojha, D. K.; Ghosh, S. K.; Samal, M. R.

We present results on the star formation activity of an optically obscured region containing an embedded cluster (S255-IR) and molecular gas between two evolved H II regions, S255 and S257. We have studied the complex using optical and near-infrared (NIR) imaging, optical spectroscopy, and radio continuum mapping at 15 GHz, along with Spitzer-IRAC results. We found that the main exciting sources of the evolved H II regions S255 and S257 and the compact H II regions associated with S255-IR are of O9.5-B3 V nature, consistent with previous observations. Our NIR observations reveal 109 likely young stellar object (YSO) candidates inmore » an area of {approx}4.'9 x 4.'9 centered on S255-IR, which include 69 new YSO candidates. To see the global star formation, we constructed the V - I/V diagram for 51 optically identified IRAC YSOs in an area of {approx}13' x 13' centered on S255-IR. We suggest that these YSOs have an approximate age between 0.1 and 4 Myr, indicating a non-coeval star formation. Using spectral energy distribution models, we constrained physical properties and evolutionary status of 31 and 16 YSO candidates outside and inside the gas ridge, respectively. The models suggest that the sources associated with the gas ridge are younger (mean age {approx}1.2 Myr) than the sources outside the gas ridge (mean age {approx}2.5 Myr). The positions of the young sources inside the gas ridge at the interface of the H II regions S255 and S257 favor a site of induced star formation.« less
Specific activity of cyclin-dependent kinase I is a new potential predictor of tumour recurrence in stage II colon cancer.

PubMed

Zeestraten, E C M; Maak, M; Shibayama, M; Schuster, T; Nitsche, U; Matsushima, T; Nakayama, S; Gohda, K; Friess, H; van de Velde, C J H; Ishihara, H; Rosenberg, R; Kuppen, P J K; Janssen, K-P

2012-01-03

There are no established biomarkers to identify tumour recurrence in stage II colon cancer. As shown previously, the enzymatic activity of the cyclin-dependent kinases 1 and 2 (CDK1 and CDK2) predicts outcome in breast cancer. Therefore, we investigated whether CDK activity identifies tumour recurrence in colon cancer. In all, 254 patients with completely resected (R0) UICC stage II colon cancer were analysed retrospectively from two independent cohorts from Munich (Germany) and Leiden (Netherlands). None of the patients received adjuvant treatment. Development of distant metastasis was observed in 27 patients (median follow-up: 86 months). Protein expression and activity of CDKs were measured on fresh-frozen tumour samples. Specific activity (SA) of CDK1 (CDK1SA), but not CDK2, significantly predicted distant metastasis (concordance index=0.69, 95% confidence interval (CI): 0.55-0.79, P=0.036). Cutoff derivation by maximum log-rank statistics yielded a threshold of CDK1SA at 11 (SA units, P=0.029). Accordingly, 59% of patients were classified as high-risk (CDK1SA ≥11). Cox proportional hazard analysis revealed CDK1SA as independent prognostic variable (hazard ratio=6.2, 95% CI: 1.44-26.9, P=0.012). Moreover, CKD1SA was significantly elevated in microsatellite-stable tumours. Specific activity of CDK1 is a promising biomarker for metastasis risk in stage II colon cancer.
Neuroprotective Effects and Mechanisms of Curcumin-Cu(II) and -Zn(II) Complexes Systems and Their Pharmacological Implications.

PubMed

Yan, Fa-Shun; Sun, Jian-Long; Xie, Wen-Hai; Shen, Liang; Ji, Hong-Fang

2017-12-28

Alzheimer's disease (AD) is the main form of dementia and has a steadily increasing prevalence. As both oxidative stress and metal homeostasis are involved in the pathogenesis of AD, it would be interesting to develop a dual function agent, targeting the two factors. Curcumin, a natural compound isolated from the rhizome of Curcuma longa , is an antioxidant and can also chelate metal ions. Whether the complexes of curcumin with metal ions possess neuroprotective effects has not been evaluated. Therefore, the present study was designed to investigate the protective effects of the complexes of curcumin with Cu(II) or Zn(II) on hydrogen peroxide (H₂O₂)-induced injury and the underlying molecular mechanisms. The use of rat pheochromocytoma (PC12) cells, a widely used neuronal cell model system, was adopted. It was revealed that curcumin-Cu(II) complexes systems possessed enhanced O₂ ·- -scavenging activities compared to unchelated curcumin. In comparison with unchelated curcumin, the protective effects of curcumin-Cu(II) complexes systems were stronger than curcumin-Zn(II) system. Curcumin-Cu(II) or -Zn(II) complexes systems significantly enhanced the superoxide dismutase, catalase, and glutathione peroxidase activities and attenuated the increase of malondialdehyde levels and caspase-3 and caspase-9 activities, in a dose-dependent manner. The curcumin-Cu(II) complex system with a 2:1 ratio exhibited the most significant effect. Further mechanistic study demonstrated that curcumin-Cu(II) or -Zn(II) complexes systems inhibited cell apoptosis via downregulating the nuclear factor κB (NF-κB) pathway and upregulating Bcl-2/Bax pathway. In summary, the present study found that curcumin-Cu(II) or -Zn(II) complexes systems, especially the former, possess significant neuroprotective effects, which indicates the potential advantage of curcumin as a promising agent against AD and deserves further study.
An unexpected Schiff base-type Ni(II) complex: Synthesis, crystal structures, fluorescence, electrochemical property and SOD-like activities

NASA Astrophysics Data System (ADS)

Chai, Lan-Qin; Zhang, Hong-Song; Huang, Jiao-Jiao; Zhang, Yu-Li

2015-02-01

An unexpected Schiff base-type Ni(II) complex, [Ni(L2)2]ṡCH3OH (HL2 = 1-(2-{[(E)-3, 5-dibromo-2-hydroxybenzylidene]amino}phenyl)ethanone oxime), has been synthesized via complexation of Ni(II) acetate tetrahydrate with HL1 (2-(3,5-dibromo-2-hydroxyphenyl)-4-methyl-1,2-dihydroquinazoline 3-oxide) originally. HL1 and its corresponding Ni(II) complex were characterized by IR, 1H NMR spectra, as well as by elemental analysis, UV-Vis and emission spectroscopy, respectively. Crystal structures of the ligand and complex have been determined by single-crystal X-ray diffraction. Each complex links two other molecules into an infinite 1-D chain via intermolecular hydrogen bonding interactions. Moreover, the electrochemical property of the nickle complex was studied by cyclic voltammetry. In addition, SOD-like activities of HL1 and Ni(II) complex were also investigated.
Antimicrobial Activity and Urease Inhibition of Schiff Bases Derived from Isoniazid and Fluorinated Benzaldehydes and of Their Copper(II) Complexes.

PubMed

Habala, Ladislav; Varényi, Samuel; Bilková, Andrea; Herich, Peter; Valentová, Jindra; Kožíšek, Jozef; Devínsky, Ferdinand

2016-12-17

In order to evaluate the influence of substitution on biological properties of Schiff bases and their metal complexes, a series of differently substituted fluorine-containing Schiff bases starting from the drug isoniazid (isonicotinylhydrazide) were prepared and their structures were established by single-crystal X-ray diffraction. Also, four copper(II) complexes of these Schiff bases were synthesized. The prepared compounds were evaluated for their antimicrobial activity and urease inhibition. Two of the Schiff bases exerted activity against C. albicans . All copper(II) complexes showed excellent inhibitory properties against jack bean urease, considerably better than that of the standard inhibitor acetohydroxamic acid.
Synthesis, characterization and biological activity of Cu(II), Ni(II) and Zn(II) complexes of biopolymeric Schiff bases of salicylaldehydes and chitosan.

PubMed

de Araújo, Eliene Leandro; Barbosa, Hellen Franciane Gonçalves; Dockal, Edward Ralph; Cavalheiro, Éder Tadeu Gomes

2017-02-01

Schiff bases have been prepared from biopolymer chitosan and salicylaldehyde, 5-methoxysalicylaldehyde, and 5-nitrosalicylaldehyde. Ligands were synthesized in a 1:1.5mol ratio, and their Cu(II), Ni(II) and Zn(II) complexes in a 1:1mol ratio (ligand:metal). Ligands were characterized by 1 H NMR and FTIR, resulting in degrees of substitution from 43.7 to 78.7%. Complexes were characterized using FTIR, electronic spectra, XPRD. The compounds were confirmed by the presence of an imine bond stretching in the 1630-1640cm -1 and νMetal-N and νMetal-O at <600cm -1 . Electronic spectra revealed that both Cu(II) and Ni(II) complexes present a square plane geometry. The crystallinity values were investigated by X-ray powder diffraction. Thermal behavior of all compounds was evaluated by TGA/DTG and DTA curves with mass losses related to dehydration and decomposition, with characteristic events for ligand and complexes. Schiff base complexes presented lower thermal stability and crystallinity than the starting chitosan. Residues were the metallic oxides as confirmed by XPRD, whose amounts were used in the calculation of the percentage of complexed metal ions. Surface morphologies were analyzed with SEM-EDAX. Preliminary cytotoxicity tests were performed using MTT assay with HeLa cells. Despite the differences in solubility, the free bases presented relatively low toxicity. Copyright © 2016 Elsevier B.V. All rights reserved.
Synthesis, characterization and anti-microbial activity of a novel macrocyclic ligand derived from the reaction of 2,6-pyridinedicarboxylic acid with homopiperazine and its Co(II), Ni(II), Cu(II), and Zn(II) complexes

NASA Astrophysics Data System (ADS)

Soleimani, Esmaiel

2011-05-01

The preparation of a novel macrocyclic ligand ( 1), N,N'-diethylhomopiperazinyl,2,6-pyridinedicarboxylate and its Co(II), Ni(II), Cu(II), and Zn(II) complexes are described. The ligand was prepared in EtOH from the reaction of dipotassium salt of 2,6-pyridinedicarboxylic acid with 1,2-dibromoethane in the presence of homopiperazine. Reaction of macrocyclic ligand ( 1) in EtOH with CoCl 2.6H 2O, NiCl 2.6H 2O, CuCl 2.2H 2O, and ZnCl 2·2H 2O yielded the complexes with the general formula [M(L)Cl 2] {where M = Co(II) ( 2), Ni(II) ( 3), Cu(II) ( 4), Zn ( 5), respectively}. The analysis of IR, 1H and 13C NMR spectral data of macrocyclic ligand ( 1) and its Zn(II) complex ( 5) together with their molar conductivity values, and the magnetic moments of the complexes suggest that the macrocyclic ligand ( 1) is bonded to metal(II) ions through two oxygen atoms of ester moiety and the two nitrogen atoms of homopiperazine ring. The electronic spectral data of these complexes in DMSO are in good agreement with the octahedral coordination of M(II) ions. The ligand field parameters for these complexes, i.e. splitting energy and Racah parameter were calculated to be 14,945 and 673 cm -1 for the Co(II) ( 2), 16,260 and 774 cm -1 for the Ni(II) ( 3) complexes respectively. The spliting energy of 17,262 cm -1 was obtained for the Cu(II) complex ( 4).
Macrocyclic receptor showing extremely high Sr(II)/Ca(II) and Pb(II)/Ca(II) selectivities with potential application in chelation treatment of metal intoxication.

PubMed

Ferreirós-Martínez, Raquel; Esteban-Gómez, David; Tóth, Éva; de Blas, Andrés; Platas-Iglesias, Carlos; Rodríguez-Blas, Teresa

2011-04-18

Herein we report a detailed investigation of the complexation properties of the macrocyclic decadentate receptor N,N'-Bis[(6-carboxy-2-pyridil)methyl]-4,13-diaza-18-crown-6 (H(2)bp18c6) toward different divalent metal ions [Zn(II), Cd(II), Pb(II), Sr(II), and Ca(II)] in aqueous solution. We have found that this ligand is especially suited for the complexation of large metal ions such as Sr(II) and Pb(II), which results in very high Pb(II)/Ca(II) and Pb(II)/Zn(II) selectivities (in fact, higher than those found for ligands widely used for the treatment of lead poisoning such as ethylenediaminetetraacetic acid (edta)), as well as in the highest Sr(II)/Ca(II) selectivity reported so far. These results have been rationalized on the basis of the structure of the complexes. X-ray crystal diffraction, (1)H and (13)C NMR spectroscopy, as well as theoretical calculations at the density functional theory (B3LYP) level have been performed. Our results indicate that for large metal ions such as Pb(II) and Sr(II) the most stable conformation is Δ(δλδ)(δλδ), while for Ca(II) our calculations predict the Δ(λδλ)(λδλ) form being the most stable one. The selectivity that bp18c6(2-) shows for Sr(II) over Ca(II) can be attributed to a better fit between the large Sr(II) ions and the relatively large crown fragment of the ligand. The X-ray crystal structure of the Pb(II) complex shows that the Δ(δλδ)(δλδ) conformation observed in solution is also maintained in the solid state. The Pb(II) ion is endocyclically coordinated, being directly bound to the 10 donor atoms of the ligand. The bond distances to the donor atoms of the pendant arms (2.55-2.60 Å) are substantially shorter than those between the metal ion and the donor atoms of the crown moiety (2.92-3.04 Å). This is a typical situation observed for the so-called hemidirected compounds, in which the Pb(II) lone pair is stereochemically active. The X-ray structures of the Zn(II) and Cd(II) complexes show that
Production and Isomeric Distribution of Xanthylium Cation Pigments and Their Precursors in Wine-like Conditions: Impact of Cu(II), Fe(II), Fe(III), Mn(II), Zn(II), and Al(III).

PubMed

Guo, Anque; Kontoudakis, Nikolaos; Scollary, Geoffrey R; Clark, Andrew C

2017-03-22

This study establishes the influence of Cu(II), Fe(II), Fe(III), Zn(II), Al(III), and Mn(II) on the oxidative production of xanthylium cations from (+)-catechin and either tartaric acid or glyoxylic acid in model wine systems. The reaction was studied at 25 °C using UHPLC and LC-HRMS for the analysis of phenolic products and their isomeric distribution. In addition to the expected products, a colorless product, tentatively assigned as a lactone, was detected for the first time. The results show the importance of Fe ions and a synergistic influence of Mn(II) in degrading tartaric acid to glyoxylic acid, whereas the other metal ions had minimal activity in this mechanistic step. Fe(II) and Fe(III) were shown to mediate the (+)-catechin-glyoxylic acid addition reaction, a role previously attributed to only Cu(II). Importantly, the study demonstrates that C-8 addition products of (+)-catechin are promoted by Cu(II), whereas C-6 addition products are promoted by Fe ions.
Pb(II) adsorption by a novel activated carbon - alginate composite material. A kinetic and equilibrium study.

PubMed

Cataldo, Salvatore; Gianguzza, Antonio; Milea, Demetrio; Muratore, Nicola; Pettignano, Alberto

2016-11-01

The adsorption capacity of an activated carbon - calcium alginate composite material (ACAA-Ca) has been tested with the aim of developing a new and more efficient adsorbent material to remove Pb(II) ion from aqueous solution. The study was carried out at pH=5, in NaCl medium and in the ionic strength range 0.1-0.75molL -1 . Differential Pulse Anodic Stripping Voltammetry (DP-ASV) technique was used to check the amount of Pb(II) ion removed during kinetic and equilibrium experiments. Different kinetic (pseudo first order, pseudo second order and Vermuelen) and equilibrium (Langmuir and Freundlich) models were used to fit experimental data, and were statistically compared. Calcium alginate (AA-Ca) improves the adsorption capacity (q m ) of active carbon (AC) in the ACAA-Ca adsorbent material (e.g., q m =15.7 and 10.5mgg -1 at I=0.25molL -1 , for ACAA-Ca and AC, respectively). SEM-EDX and thermogravimetric (TGA) measurements were carried out in order to characterize the composite material. The results of the speciation study on the Pb(II) solution and of the characterization of the ACAA-Ca and of the pristine AA-Ca and AC were evaluated in order to explain the specific contribution of AC and AA-Ca to the adsorption of the metal ion. Copyright © 2016 Elsevier B.V. All rights reserved.
Biosorption of toxic lead (II) ions using tomato waste (Solanum lycopersicum) activated by NaOH

NASA Astrophysics Data System (ADS)

Permatasari, Diah; Heraldy, Eddy; Lestari, Witri Wahyu

2016-02-01

This research present to uptake lead (II) ion from aqueous solutions by activated tomato waste. Biosorbent were characterized by applying Fourier Transform Infrared Spectroscopy (FTIR) and Surface Area Analyzer (SAA). The biosorption investigated with parameters including the concentration of NaOH, effects of solution pH, biosorbent dosage, contact time,and initial metal concentration. Experimental data were analyzed in terms of two kinetic model such us the pseudo-first order and pseudo-second order. Langmuir and Freundlich isotherm models were applied todescribe the biosorption process. According to the experiment, the optimum concentration of NaOH was achieved at 0.1 M. The maximum % lead (II) removal was achieved at pH 4 with 94.5%. Optimum biosorbentdosage were found as 0.1 g/25 mL solution while optimum contact time were found at 75 minutes. The results showed that the biosorption processes of Lead (II) followed pseudo-second order kinetics. Langmuir adsorption isotherm was found fit the adsorption data with amaximum capacity of 24.079 mg/g with anadsorption energy of 28.046 kJ/mol.
Renal nerve stimulation leads to the activation of the Na+/H+ exchanger isoform 3 via angiotensin II type I receptor.

PubMed

Pontes, Roberto B; Crajoinas, Renato O; Nishi, Erika E; Oliveira-Sales, Elizabeth B; Girardi, Adriana C; Campos, Ruy R; Bergamaschi, Cássia T

2015-04-15

Renal nerve stimulation at a low frequency (below 2 Hz) causes water and sodium reabsorption via α1-adrenoreceptor tubular activation, a process independent of changes in systemic blood pressure, renal blood flow, or glomerular filtration rate. However, the underlying mechanism of the reabsorption of sodium is not fully understood. Since the sympathetic nervous system and intrarenal ANG II appear to act synergistically to mediate the process of sodium reabsorption, we hypothesized that low-frequency acute electrical stimulation of the renal nerve (ESRN) activates NHE3-mediated sodium reabsorption via ANG II AT1 receptor activation in Wistar rats. We found that ESRN significantly increased urinary angiotensinogen excretion and renal cortical ANG II content, but not the circulating angiotensinogen levels, and also decreased urinary flow and pH and sodium excretion via mechanisms independent of alterations in creatinine clearance. Urinary cAMP excretion was reduced, as was renal cortical PKA activity. ESRN significantly increased NHE3 activity and abundance in the apical microvillar domain of the proximal tubule, decreased the ratio of phosphorylated NHE3 at serine 552/total NHE3, but did not alter total cortical NHE3 abundance. All responses mediated by ESRN were completely abolished by a losartan-mediated AT1 receptor blockade. Taken together, our results demonstrate that higher NHE3-mediated proximal tubular sodium reabsorption induced by ESRN occurs via intrarenal renin angiotensin system activation and triggering of the AT1 receptor/inhibitory G-protein signaling pathway, which leads to inhibition of cAMP formation and reduction of PKA activity. Copyright © 2015 the American Physiological Society.
Biologically active Schiff bases containing thiophene/furan ring and their copper(II) complexes: Synthesis, spectral, nonlinear optical and density functional studies

NASA Astrophysics Data System (ADS)

Gündüzalp, Ayla Balaban; Özsen, İffet; Alyar, Hamit; Alyar, Saliha; Özbek, Neslihan

2016-09-01

Schiff bases; 1,8-bis(thiophene-2-carboxaldimine)-p-menthane (L1) and 1,8-bis(furan-2-carboxaldimine)-p-menthane (L2) have been synthesized and characterized by elemental analysis, 1Hsbnd 13C NMR, UV-vis, FT-IR and LC-MS methods. 1H and 13C shielding tensors for L1 and L2 were calculated with GIAO/DFT/B3LYP/6-311++G(d,p) methods in CDCl3. The vibrational band assignments, nonlinear optical (NLO) activities, frontier molecular orbitals (FMOs) and absorption spectrum have been investigated by the same basis set. Schiff base-copper(II) complexes have been synthesized and structurally characterized with spectroscopic methods, magnetic and conductivity measurements. The spectroscopic data suggest that Schiff base ligands coordinate through azomethine-N and thiophene-S/furan-O donors (as SNNS and ONNO chelating systems) to give a tetragonal geometry around the copper(II) ions. Schiff bases and Cu(II) complexes have been screened for their biological activities on different species of pathogenic bacteria, those are, Gram positive bacteria: Bacillus subtitilus, Yersinia enterotica, Bacillus cereus, Listeria monocytogenes, Micrococcus luteus and Gram negative bacteria: Escherichia coli, Pseudomonas aeroginosa, Shigella dysenteriae, Salmonella typhi, Klebsiella pseudomonas by using microdilution technique (MIC values in mM). Biological activity results show that Cu(II) complexes have higher activities than parent ligands and metal chelation may affect significantly the antibacterial behavior of the organic ligands.
20 CFR 404.111 - When we consider a person fully insured based on World War II active military or naval service.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false When we consider a person fully insured based on World War II active military or naval service. 404.111 Section 404.111 Employees' Benefits SOCIAL... States during World War II; (b) The person died within three years after separation from service and...
20 CFR 404.111 - When we consider a person fully insured based on World War II active military or naval service.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false When we consider a person fully insured based on World War II active military or naval service. 404.111 Section 404.111 Employees' Benefits SOCIAL... States during World War II; (b) The person died within three years after separation from service and...

20 CFR 404.111 - When we consider a person fully insured based on World War II active military or naval service.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false When we consider a person fully insured based on World War II active military or naval service. 404.111 Section 404.111 Employees' Benefits SOCIAL... States during World War II; (b) The person died within three years after separation from service and...
20 CFR 404.111 - When we consider a person fully insured based on World War II active military or naval service.

Code of Federal Regulations, 2011 CFR

2011-04-01

... on World War II active military or naval service. 404.111 Section 404.111 Employees' Benefits SOCIAL... Quarters of Coverage Fully Insured Status § 404.111 When we consider a person fully insured based on World... States during World War II; (b) The person died within three years after separation from service and...
Discovery of Type II Inhibitors of TGFβ-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Li; Nomanbhoy, Tyzoon; Gurbani, Deepak

Here, we developed a pharmacophore model for type II inhibitors that was used to guide the construction of a library of kinase inhibitors. Kinome-wide selectivity profiling of the library resulted in the identification of a series of 4-substituted 1H-pyrrolo[2,3-b]pyridines that exhibited potent inhibitory activity against two mitogen-activated protein kinases (MAPKs), TAK1 (MAP3K7) and MAP4K2, as well as pharmacologically well interrogated kinases such as p38α (MAPK14) and ABL. Further investigation of the structure–activity relationship (SAR) resulted in the identification of potent dual TAK1 and MAP4K2 inhibitors such as 1 (NG25) and 2 as well as MAP4K2 selective inhibitors such as 16more » and 17. Some of these inhibitors possess good pharmacokinetic properties that will enable their use in pharmacological studies in vivo. Lastly, a 2.4 Å cocrystal structure of TAK1 in complex with 1 confirms that the activation loop of TAK1 assumes the DFG-out conformation characteristic of type II inhibitors.« less
Discovery of Type II Inhibitors of TGFβ-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2)

DOE PAGES

Tan, Li; Nomanbhoy, Tyzoon; Gurbani, Deepak; ...

2014-07-17

Here, we developed a pharmacophore model for type II inhibitors that was used to guide the construction of a library of kinase inhibitors. Kinome-wide selectivity profiling of the library resulted in the identification of a series of 4-substituted 1H-pyrrolo[2,3-b]pyridines that exhibited potent inhibitory activity against two mitogen-activated protein kinases (MAPKs), TAK1 (MAP3K7) and MAP4K2, as well as pharmacologically well interrogated kinases such as p38α (MAPK14) and ABL. Further investigation of the structure–activity relationship (SAR) resulted in the identification of potent dual TAK1 and MAP4K2 inhibitors such as 1 (NG25) and 2 as well as MAP4K2 selective inhibitors such as 16more » and 17. Some of these inhibitors possess good pharmacokinetic properties that will enable their use in pharmacological studies in vivo. Lastly, a 2.4 Å cocrystal structure of TAK1 in complex with 1 confirms that the activation loop of TAK1 assumes the DFG-out conformation characteristic of type II inhibitors.« less
Effect of Cu(II) coordination compounds on the activity of antioxidant enzymes catalase and superoxide dismutase in patients with colorectal cancer.

PubMed

Kubiak, Katarzyna; Malinowska, Katarzyna; Langer, Ewa; Dziki, Łukasz; Dziki, Adam; Majsterek, Ireneusz

2011-03-01

Colorectal cancer (CRC) is a serious medical and economical problem of our times. It is the most common gastrointestinal cancer in the world. In Poland, the treatment and detection of CRC are poorly developed and the pathogenesis is still unclear. One hypothesis suggests a role of reactive oxygen species (ROS) in the pathogenesis of CRC. Experimental studies in recent years confirm the participation of ROS in the initiation and promotion of CRC. The aim of the study was to examine the effect of the following coordination compounds coordination compounds: dinitrate (V) tetra(3,4,5-trimethyl-N1-pyrazole-κN2) copper(II), dichloro di(3,4,5-trimethyl-N1-pyrazole-κN2) copper(II), dinitrate (V) di(1,4,5-trimethyl-N1-pyrazole-κN2) copper(II), dichloro di(1,3,4,5-tetramethyl-N1-pyrazole-κN2) copper(II) on the activity of antioxidant enzymes superoxide dismutase (SOD, ZnCu-SOD) and catalase (CAT) in a group of patients with colorectal cancer (CRC) and in the control group consisting of patients with minor gastrointestinal complaints. The study was conducted in 20 patients diagnosed with colorectal cancer at the age of 66.5±10.2 years (10 men and 10 women) versus the control group of 20 people (10 men and 10 women) aged 57.89±17.10 years without cancer lesions in the biological material - hemolysate prepared in a proportion of 1ml of water per 1 ml of blood. CAT activity was measured by the Beers method (1952), while SOD activity was measured by the Misra and Fridovich method (1972). We found that patients with CRC showed a statistically significant decrease of SOD and CAT activity (CAT - 12,75±1.97 U/g Hb, SOD - 1111.52±155.52 U/g Hb) in comparison with the control group (CAT - 19.65±2,17 U/g Hb, SOD - 2046.26±507.22 U/g Hb). Simultaneously, we observed that the investigated coordination compounds of Cu(II) significantly increased the antioxidant activity of CAT and SOD in patients with CRC (mean: CAT 25.23±4.86 U/g Hb, SOD - 3075.96±940.20 U/g Hb). Patients with
Specific activity of class II histone deacetylases in human breast cancer cells

PubMed Central

Duong, Vanessa; Bret, Caroline; Altucci, Lucia; Mai, Antonello; Duraffourd, Céline; Loubersac, Julie; Harmand, Pierre-Olivier; Bonnet, Sandrine; Valente, Sergio; Maudelonde, Thierry; Cavailles, Vincent; Boulle, Nathalie

2008-01-01

Although numerous studies have underlined the role of HDACs in breast physiology and tumorigenesis, little is known on the particular contribution of the various classes of HDACs in these processes. Using ERα-positive MCF-7 breast cancer cells, the effects of MC1575 and MC1568, two novel class II specific HDAC inhibitors (HDI), were analyzed on cell proliferation, apoptosis and estrogen signalling. The specificity of these HDIs was validated by measuring histone and α-tubulin acetylation and by the specific in vitro inhibition of recombinant HDAC4 using histone and non histone substrates, contrasting with the lack of inhibition of class I HDACs. In addition, MC1575 did not inhibit class I HDAC gene expression thus confirming the specific targeting of class II enzymes. Similar to TSA, MC1575 displayed a dose-dependent anti-proliferative effect and induced cell cycle arrest although this blockade occurred at a different level than TSA. Moreover, and in contrast to TSA, MC1575 had no effect on MCF-7 cells apoptosis. Interestingly, MC1575 was able to increase p2lwaf1/CIP1 mRNA levels but did not regulate the expression of other genes such as cyclin D1, p27, p14ARF, Bcl2, Baxα, Trail-R1 and -R2. Finally, MC1575 strongly induced ERβ gene expression but did not decrease ERα expression nor did it switch hydroxy-tamoxifen to an agonist activity. Altogether, these data suggest that the class II HDAC sub-family may exert specific roles in breast cancer progression and estrogen-dependence. PMID:19074835
Alpha 2-macroglobulin capture allows detection of mast cell chymase in serum and creates a reservoir of angiotensin II-generating activity.

PubMed

Raymond, Wilfred W; Su, Sharon; Makarova, Anastasia; Wilson, Todd M; Carter, Melody C; Metcalfe, Dean D; Caughey, George H

2009-05-01

Human chymase is a highly efficient angiotensin II-generating serine peptidase expressed by mast cells. When secreted from degranulating cells, it can interact with a variety of circulating antipeptidases, but is mostly captured by alpha(2)-macroglobulin, which sequesters peptidases in a cage-like structure that precludes interactions with large protein substrates and inhibitors, like serpins. The present work shows that alpha(2)-macroglobulin-bound chymase remains accessible to small substrates, including angiotensin I, with activity in serum that is stable with prolonged incubation. We used alpha(2)-macroglobulin capture to develop a sensitive, microtiter plate-based assay for serum chymase, assisted by a novel substrate synthesized based on results of combinatorial screening of peptide substrates. The substrate has low background hydrolysis in serum and is chymase-selective, with minimal cleavage by the chymotryptic peptidases cathepsin G and chymotrypsin. The assay detects activity in chymase-spiked serum with a threshold of approximately 1 pM (30 pg/ml), and reveals native chymase activity in serum of most subjects with systemic mastocytosis. alpha(2)-Macroglobulin-bound chymase generates angiotensin II in chymase-spiked serum, and it appears in native serum as chymostatin-inhibited activity, which can exceed activity of captopril-sensitive angiotensin-converting enzyme. These findings suggest that chymase bound to alpha(2)-macroglobulin is active, that the complex is an angiotensin-converting enzyme inhibitor-resistant reservoir of angiotensin II-generating activity, and that alpha(2)-macroglobulin capture may be exploited in assessing systemic release of secreted peptidases.
Type II thyroplasty changes cortical activation in patients with spasmodic dysphonia.

PubMed

Tateya, Ichiro; Omori, Koichi; Kojima, Hisayoshi; Naito, Yasushi; Hirano, Shigeru; Yamashita, Masaru; Ito, Juichi

2015-04-01

Spasmodic dysphonia (SD) is a complex neurological communication disorder characterized by a choked, strain-strangled vocal quality with voice stoppages in phonation. Its symptoms are exacerbated by situations where communication failures are anticipated, and reduced when talking with animals or small children. Symptoms are also reduced following selected forms of treatment. It is reasonable to assume that surgical alteration reducing symptoms would also alter brain activity, though demonstration of such a phenomenon has not been documented. The objective of this study is to reveal brain activity of SD patients before and after surgical treatment. We performed lateralization thyroplasties on three adductor SD patients and compared pre- and post-operative positron emission tomography recordings made during vocalization. Pre-operatively, cordal supplementary motor area (SMA), bilateral auditory association areas, and thalamus were activated while reading aloud. Such activity was not observed in normal subjects. Type II thyroplasty was performed according to Isshiki's method and the strained voice was significantly reduced or eliminated in all three patients. Post-operative PET showed normal brain activation pattern with a significant decrease in cordal SMA, bilateral auditory association areas and thalamus, and a significant increase in rostral SMA compared with pre-operative recordings. This is the first report showing that treatment to a peripheral organ, which reverses voice symptoms, also reverses dysfunctional patterns of the central nervous system in patients with SD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
The Duffy binding protein (PkDBPαII) of Plasmodium knowlesi from Peninsular Malaysia and Malaysian Borneo show different binding activity level to human erythrocytes.

PubMed

Lim, Khai Lone; Amir, Amirah; Lau, Yee Ling; Fong, Mun Yik

2017-08-11

The zoonotic Plasmodium knowlesi is a major cause of human malaria in Malaysia. This parasite uses the Duffy binding protein (PkDBPαII) to interact with the Duffy antigen receptor for chemokines (DARC) receptor on human and macaque erythrocytes to initiate invasion. Previous studies on P. knowlesi have reported distinct Peninsular Malaysia and Malaysian Borneo PkDBPαII haplotypes. In the present study, the differential binding activity of these haplotypes with human and macaque (Macaca fascicularis) erythrocytes was investigated. The PkDBPαII of Peninsular Malaysia and Malaysian Borneo were expressed on the surface of COS-7 cells and tested with human and monkey erythrocytes, with and without anti-Fy6 (anti-Duffy) monoclonal antibody treatment. Binding activity level was determined by counting the number of rosettes formed between the transfected COS-7 cells and the erythrocytes. Anti-Fy6 treatment was shown to completely block the binding of human erythrocytes with the transfected COS-7 cells, thus verifying the specific binding of human DARC with PkDBPαII. Interestingly, the PkDBPαII of Peninsular Malaysia displayed a higher binding activity with human erythrocytes when compared with the Malaysian Borneo PkDBPαII haplotype (mean number of rosettes formed = 156.89 ± 6.62 and 46.00 ± 3.57, respectively; P < 0.0001). However, no difference in binding activity level was seen in the binding assay using M. fascicularis erythrocytes. This study is the first report of phenotypic difference between PkDBPαII haplotypes. The biological implication of this finding is yet to be determined. Therefore, further studies need to be carried out to determine whether this differential binding level can be associated with severity of knowlesi malaria in human.
Angiotensin II increases phosphodiesterase 5A expression in vascular smooth muscle cells: A mechanism by which angiotensin II antagonizes cGMP signaling

PubMed Central

Kim, Dongsoo; Aizawa, Toru; Wei, Heng; Pi, Xinchun; Rybalkin, Sergei D.; Berk, Bradford C.; Yan, Chen

2014-01-01

Angiotensin II (Ang II) and nitric oxide (NO)/natriuretic peptide (NP) signaling pathways mutually regulate each other. Imbalance of Ang II and NO/NP has been implicated in the pathophysiology of many vascular diseases. cGMP functions as a key mediator in the interaction between Ang II and NO/NP. Cyclic nucleotide phosphodiesterase 5A (PDE5A) is important in modulating cGMP signaling by hydrolyzing cGMP in vascular smooth muscle cells (VSMC). Therefore, we examined whether Ang II negatively modulates intracellular cGMP signaling in VSMC by regulating PDE5A. Ang II rapidly and transiently increased PDE5A mRNA levels in rat aortic VSMC. Upregulation of PDE5A mRNA was associated with a time-dependent increase of both PDE5 protein expression and activity. Increased PDE5A mRNA level was transcription-dependent and mediated by the Ang II type 1 receptor. Ang II-mediated activation of extracellular signal-regulated kinases 1/2 (ERK1/2) was essential for Ang II-induced PDE5A upregulation. Pretreatment of VSMC with Ang II inhibited C-type NP (CNP) stimulated cGMP signaling, such as cGMP dependent protein kinase (PKG)-mediated phosphorylation of vasodilator-stimulated-phosphoprotein (VASP). Ang II-mediated inhibition of PKG was blocked when PDE5 activity was decreased by selective PDE5 inhibitors, suggesting that upregulation of PDE5A expression is an important mechanism for Ang II to attenuate cGMP signaling. PDE5A may also play a critical role in the growth promoting effects of Ang II because inhibition of PDE5A activity significantly decreased Ang II-stimulated VSMC growth. These observations establish a new mechanism by which Ang II antagonizes cGMP signaling and stimulates VSMC growth. PMID:15623434
Retrotransposon Tf1 is targeted to pol II promoters by transcription activators

PubMed Central

Leem, Young-Eun; Ripmaster, Tracy; Kelly, Felice; Ebina, Hirotaka; Heincelman, Marc; Zhang, Ke; Grewal, Shiv I. S.; Hoffman, Charles S.; Levin, Henry L.

2008-01-01

SUMMARY The LTR-retrotransposon Tf1 preserves the coding capacity of its host Schizosaccharomyces pombe by integrating upstream of open reading frames (ORFs). To determine which features of the target sites were recognized by the transposon, we introduced plasmids containing candidate insertion sites into S. pombe and mapped the positions of integration. We found that Tf1 was targeted specifically to the promoters of pol II transcribed genes. A detailed analysis of integration in plasmids that contained either ade6 or fbp1 revealed insertions occurred in the promoters at positions where transcription factors bound. Further experiments revealed that the activator Atf1p and its binding site were required for directing integration to the promoter of fbp1. An interaction between Tf1 integrase and Atf1p was observed indicating that integration at fbp1 was mediated by the activator bound to its promoter. Surprisingly we found Tf1 contained sequences that activated transcription and these substituted for elements of the ade6 promoter disrupted by integration. PMID:18406330
Retrotransposon Tf1 is targeted to Pol II promoters by transcription activators.

PubMed

Leem, Young-Eun; Ripmaster, Tracy L; Kelly, Felice D; Ebina, Hirotaka; Heincelman, Marc E; Zhang, Ke; Grewal, Shiv I S; Hoffman, Charles S; Levin, Henry L

2008-04-11

The LTR-retrotransposon Tf1 preserves the coding capacity of its host Schizosaccharomyces pombe by integrating upstream of open reading frames (ORFs). To determine which features of the target sites were recognized by the transposon, we introduced plasmids containing candidate insertion sites into S. pombe and mapped the positions of integration. We found that Tf1 was targeted specifically to the promoters of Pol II-transcribed genes. A detailed analysis of integration in plasmids that contained either ade6 or fbp1 revealed insertions occurred in the promoters at positions where transcription factors bound. Further experiments revealed that the activator Atf1p and its binding site were required for directing integration to the promoter of fbp1. An interaction between Tf1 integrase and Atf1p was observed, indicating that integration at fbp1 was mediated by the activator bound to its promoter. Surprisingly, we found Tf1 contained sequences that activated transcription, and these substituted for elements of the ade6 promoter disrupted by integration.
Antimalarial, antimicrobial, cytotoxic, DNA interaction and SOD like activities of tetrahedral copper(II) complexes

NASA Astrophysics Data System (ADS)

Mehta, Jugal V.; Gajera, Sanjay B.; Patel, Mohan N.

2015-02-01

The mononuclear copper(II) complexes with P, O-donor ligand and different fluoroquinolones have been synthesized and characterized by elemental analysis, electronic spectra, TGA, EPR, FT-IR and LC-MS spectroscopy. An antimicrobial efficiency of the complexes has been tested against five different microorganisms in terms of minimum inhibitory concentration (MIC) and displays very good antimicrobial activity. The binding strength and binding mode of the complexes with Herring Sperm DNA (HS DNA) have been investigated by absorption titration and viscosity measurement studies. The studies suggest the classical intercalative mode of DNA binding. Gel electrophoresis assay determines the ability of the complexes to cleave the supercoiled form of pUC19 DNA. Synthesized complexes have been tested for their SOD mimic activity using nonenzymatic NBT/NADH/PMS system and found to have good antioxidant activity. All the complexes show good cytotoxic and in vitro antimalarial activities.
Free radical scavenging activity and neuroprotective potentials of D138, one Cu(II)/Zn(II) Schiff-base complex derived from N,N'-bis(2-hydroxynaphthylmethylidene)-1,3-propanediamine.

PubMed

Wang, Che; Cai, Zheng-Xu; You, Zhong-Lu; Guo, Hui-Shu; Shang, De-Jing; Wang, Xiao-Ling; Zhang, Liang; Ma, Li-Jie; Tan, Jun; Le, Wei-Dong; Li, Song

2014-09-01

There is increasing evidence that free radicals play an important role in neuronal damages induced by diabetes mellitus or cerebral ischemia insults. Antioxidants with free radical scavenging activities have been shown to be beneficial and neuroprotective for these pathological conditions. Here, we report free radical scavenging activity and neuroprotective potential of D138, one copper(II)/zinc(II) Schiff-base complex derived from N,N'-2(2-hydroxynaphthylmethylidene)-1,3-propanediamine. The data from three in vitro assays, 2,2-diphenyl-1-picrylhydrazyl assay, nitro blue tetrazolium assay and hydroxyl radical scavenging assay, indicated that D138 presented a potent free radical scavenging activity. The neuroprotective and antioxidative effects of D138 were further evaluated in vivo using bilateral common carotid artery occlusion (BCCAO) mouse model and streptozotocin (STZ) diabetic mouse model. Our results indicated that treatment of D138 significantly ameliorated the hippocampal neuronal damage and the oxidative stress levels in these animal models. Moreover, D138 also reversed the behavioral deficiencies induced by BCCAO or STZ, as assessed by Y-maze test and fear conditioning test. In conclusion, all these findings support that D138 exerts free radical scavenging and neuroprotective activities and has the potentials to be a potent therapeutic candidate for brain oxidative damage induced by cerebral ischemia or diabetes mellitus.
Effect of short peptides containing lysine and epsilon-aminocaproic acid on fibrinolytic activity of plasmin and topoisomerase II action on supercoiled DNA.

PubMed

Midura-Nowaczek, Krystyna; Purwin, Maciej; Markowska, Agnieszka; Drozdowska, Danuta; Bruzgo, Magdalena

2013-01-01

Effects of eight short peptides containing lysine and epsilon-aminocaproic acid (EACA) on prolongation of the clot lysis time, as well as hemolytic and antibacterial activities were investigated. Interaction with plasmids pBR322 and pUC19 with the use of ethidium bromide assay and determination of influence on the activity of topoisomerase I and II were also tested. Examined compounds inhibited fibrinolytic activity of plasmin and five of them were more active than EACA. Amides of dipeptides were most active antifibrinolytics (IC50 < 0.2 mM). According to the obtained data, the significant inhibition of fibrinolytic activity of plasmin was not associated with hemolytic effects. Examined compounds did not show antibacterial activity (MIC > 512 mg/L). DNA binding effects determined with the use of ethidium bromide were weak for all peptides and similar to those observed with EACA. Six compounds inhibited topoisomerase II action on supercoiled DNA.
Design, spectral characterization, thermal, DFT studies and anticancer cell line activities of Co(II), Ni(II) and Cu(II) complexes of Schiff bases derived from 4-amino-5-(pyridin-4-yl)-4H-1,2,4-triazole-3-thiol.

PubMed

Tyagi, Prateek; Chandra, Sulekh; Saraswat, B S; Yadav, Deepak

2015-06-15

A series of two biologically active Schiff base ligands L(1), L(2) have been synthesized in equimolar reaction of 4-amino-5-(pyridin-4-yl)-4H-1,2,4-triazole-3-thiol with thiophene-2-carbaldehyde and furan-2-carbaldehyde. The synthesized Schiff bases were used for complexation with different metal ions like Co(II), Ni(II) and Cu(II) by using a molar ratio of ligand: metal as 1:1 and 2:1. The characterization of Schiff bases and metal complexes was done by (1)H NMR, UV-Vis, TGA, IR, mass spectrometry and molar conductivity studies. The in DFT studies the geometries of Schiff bases and metal complexes were fully optimized with respect to the energy using the 6-31+g(d,p) basis set. On the basis of the spectral studies an octahedral geometry has been assigned for Co(II), Ni(II) and Cu(II) complexes. The effect of these complexes on proliferation of human breast cancer cell line (MCF-7) and human hepatocellular liver carcinoma cell line (Hep-G2) were studied and compared with those of free ligand. The anticancer cell line results reveal that all metal complexes show moderate to significant % cytotoxicity on cell line HepG2 and MCF-7. Copyright © 2015 Elsevier B.V. All rights reserved.
Antibody-directed neutralization of annexin II (ANX II) inhibits neoangiogenesis and human breast tumor growth in a xenograft model.

PubMed

Sharma, Meena; Blackman, Marc R; Sharma, Mahesh C

2012-02-01

Activation of the fibrinolytic pathway has long been associated with human breast cancer. Plasmin is the major end product of the fibrinolytic pathway and is critical for normal physiological functions. The mechanism by which plasmin is generated in breast cancer is not yet fully described. We previously identified annexin II (ANX II), a fibrinolytic receptor, in human breast tumor tissue samples and observed a strong positive correlation with advanced stage cancer (Sharma et al., 2006a). We further demonstrated that tissue plasminogen activator (tPA) binds to ANX II in invasive breast cancer MDA-MB231cells, which leads to plasmin generation (Sharma et al., 2010). We hypothesize that ANX II-dependent plasmin generation in breast tumor is necessary to trigger the switch to neoangiogenesis, thereby stimulating a more aggressive cancer phenotype. Our immunohistochemical studies of human breast tumor tissues provide compelling evidence of a strong positive correlation between ANX II expression and neoangiogenesis, and suggest that ANX II is a potential target to slow or inhibit breast tumor growth by inhibiting neoangiogenesis. We now report that administration of anti-ANX II antibody potently inhibits the growth of human breast tumor in a xenograft model. Inhibition of tumor growth is at least partly due to attenuation of neoangiogenic activity within the tumor. In vitro studies demonstrate that anti-ANX II antibody inhibits angiogenesis on three dimensional matrigel cultures by eliciting endothelial cell (EC) death likely due to apoptosis. Taken together, these data suggest that selective disruption of the fibrinolytic activity of ANX II may provide a novel strategy for specific inhibition of neoangiogenesis in human breast cancer. Published by Elsevier Inc.
Phosphorylation of rat kidney Na-K pump at Ser938 is required for rapid angiotensin II-dependent stimulation of activity and trafficking in proximal tubule cells

PubMed Central

Massey, Katherine J.; Li, Quanwen; Rossi, Noreen F.; Keezer, Susan M.; Mattingly, Raymond R.

2015-01-01

How angiotensin (ANG) II acutely stimulates the Na-K pump in proximal tubules is only partially understood, limiting insight into how ANG II increases blood pressure. First, we tested whether ANG II increases the number of pumps in plasma membranes of native rat proximal tubules under conditions of rapid activation. We found that exposure to 100 pM ANG II for 2 min, which was previously shown to increase affinity of the Na-K pump for Na and stimulate activity threefold, increased the amount of the Na-K pump in plasma membranes of native tubules by 33%. Second, we tested whether previously observed increases in phosphorylation of the Na-K pump at Ser938 were part of the stimulatory mechanism. These experiments were carried out in opossum kidney cells, cultured proximal tubules stably coexpressing the ANG type 1 (AT1) receptor, and either wild-type or a S938A mutant of rat kidney Na-K pump under conditions found by others to stimulate activity. We found that 10 min of incubation in 10 pM ANG II stimulated activity of wild-type pumps from 2.3 to 3.5 nmol K·mg protein−1·min−1 and increased the amount of the pump in the plasma membrane by 80% but had no effect on cells expressing the S938A mutant. We conclude that acute stimulation of Na-K pump activity in native rat proximal tubules includes increased trafficking to the plasma membrane and that phosphorylation at Ser938 is part of the mechanism by which ANG II directly stimulates activity and trafficking of the rat kidney Na-K pump in opossum kidney cells. PMID:26582472
Double-stranded DNA translocase activity of transcription factor TFIIH and the mechanism of RNA polymerase II open complex formation.

PubMed

Fishburn, James; Tomko, Eric; Galburt, Eric; Hahn, Steven

2015-03-31

Formation of the RNA polymerase II (Pol II) open complex (OC) requires DNA unwinding mediated by the transcription factor TFIIH helicase-related subunit XPB/Ssl2. Because XPB/Ssl2 binds DNA downstream from the location of DNA unwinding, it cannot function using a conventional helicase mechanism. Here we show that yeast TFIIH contains an Ssl2-dependent double-stranded DNA translocase activity. Ssl2 tracks along one DNA strand in the 5' → 3' direction, implying it uses the nontemplate promoter strand to reel downstream DNA into the Pol II cleft, creating torsional strain and leading to DNA unwinding. Analysis of the Ssl2 and DNA-dependent ATPase activity of TFIIH suggests that Ssl2 has a processivity of approximately one DNA turn, consistent with the length of DNA unwound during transcription initiation. Our results can explain why maintaining the OC requires continuous ATP hydrolysis and the function of TFIIH in promoter escape. Our results also suggest that XPB/Ssl2 uses this translocase mechanism during DNA repair rather than physically wedging open damaged DNA.
Development of in vivo biotransformation enzyme assays for ecotoxicity screening: In vivo measurement of phases I and II enzyme activities in freshwater planarians.

PubMed

Li, Mei-Hui

2016-08-01

The development of a high-throughput tool is required for screening of environmental pollutants and assessing their impacts on aquatic animals. Freshwater planarians can be used in rapid and sensitive toxicity bioassays. Planarians are known for their remarkable regeneration ability but much less known for their metabolic and xenobiotic biotransformation abilities. In this study, the activities of different phase I and II enzymes were determined in vivo by directly measuring fluorescent enzyme substrate disappearance or fluorescent enzyme metabolite production in planarian culture media. For phase I enzyme activity, O-deethylation activities with alkoxyresorufin could not be detected in planarian culture media. By contrast, O-deethylation activities with alkoxycoumarin were detected in planarian culture media. Increases in 7-ethoxycoumarin O-deethylase (ECOD) activities was only observed in planarians exposed to 1μM, but not 10μM, β-naphthoflavone for 24h. ECOD activity was inhibited in planarians exposed to 10 and 100μM rifampicin or carbamazepine for 24h. For phase II enzyme activity, DT-diaphorase, arylsulfatases, uridine 5'-diphospho (UDP)-glucuronosyltransferase or catechol-O-methyltransferase activity was determined in culture media containing planarians. The results of this study indicate that freshwater planarians are a promising model organism to monitor exposure to environmental pollutants or assess their impacts through the in vivo measurement of phase I and II enzyme activities. Copyright © 2016. Published by Elsevier Inc.

Synthesis, characterization and antibacterial activity of new sulfonyl hydrazone derivatives and their nickel(II) complexes

NASA Astrophysics Data System (ADS)

Özmen, Ümmühan Özdemir; Olgun, Gülçin

2008-08-01

Prophane sulfonic acid hydrazide (psh: CH 3CH 2CH 2SO 2NHNH 2) derivatives as salicylaldehydeprophanesulfonylhydrazone (salpsh), 5-methylsalicylaldehydeprophanesulfonylhydrazone (5-msalpsh), 2-hydroxyacetophenoneprophanesulfonylhydrazone (afpsh), 5-methyl-2-hydroxyacetophenoneprophanesulfonylhydrazone (5-mafpsh) and their Ni(II) complexes have been synthesized. The structure of these compounds has been investigated by using elemental analysis, FTIR, 1H NMR, LC/MS, UV-vis spectrophotometric method, magnetic susceptibility and conductivity measurements. The complexes were found to have general compositions [NiL2]. Square-planer structures are proposed for the Ni(II) complexes on the basis of magnetic evidence, electronic spectra and TGA data. Bacterial activities of sulfonyl hydrazone compounds were studied against gram-positive bacteria: Staphylococcus aureus, Bacillus subtilis, Bacillus magaterium and gram-negative bacteria: Salmonella enteritidis, Escherichia coli by using minimum inhibitory concentrations (MICs) method.
Drosophila non-muscle myosin II motor activity determines the rate of tissue folding

PubMed Central

Vasquez, Claudia G; Heissler, Sarah M; Billington, Neil; Sellers, James R; Martin, Adam C

2016-01-01

Non-muscle cell contractility is critical for tissues to adopt shape changes. Although, the non-muscle myosin II holoenzyme (myosin) is a molecular motor that powers contraction of actin cytoskeleton networks, recent studies have questioned the importance of myosin motor activity cell and tissue shape changes. Here, combining the biochemical analysis of enzymatic and motile properties for purified myosin mutants with in vivo measurements of apical constriction for the same mutants, we show that in vivo constriction rate scales with myosin motor activity. We show that so-called phosphomimetic mutants of the Drosophila regulatory light chain (RLC) do not mimic the phosphorylated RLC state in vitro. The defect in the myosin motor activity in these mutants is evident in developing Drosophila embryos where tissue recoil following laser ablation is decreased compared to wild-type tissue. Overall, our data highlights that myosin activity is required for rapid cell contraction and tissue folding in developing Drosophila embryos. DOI: http://dx.doi.org/10.7554/eLife.20828.001 PMID:28035903
Modeling the active site of [NiFe] hydrogenases and the [NiFeu] subsite of the C-cluster of carbon monoxide dehydrogenases: low-spin iron(II) versus high-spin iron(II).

PubMed

Weber, Katharina; Erdem, Özlen F; Bill, Eckhard; Weyhermüller, Thomas; Lubitz, Wolfgang

2014-06-16

A series of four [S2Ni(μ-S)2FeCp*Cl] compounds with different tetradentate thiolate/thioether ligands bound to the Ni(II) ion is reported (Cp* = C5Me5). The {S2Ni(μ-S)2Fe} core of these compounds resembles structural features of the active site of [NiFe] hydrogenases. Detailed analyses of the electronic structures of these compounds by Mössbauer and electron paramagnetic resonance spectroscopy, magnetic measurements, and density functional theory calculations reveal the oxidation states Ni(II) low spin and Fe(II) high spin for the metal ions. The same electronic configurations have been suggested for the Cred1 state of the C-cluster [NiFeu] subsite in carbon monoxide dehydrogenases (CODH). The Ni-Fe distance of ∼3 Å excludes a metal-metal bond between nickel and iron, which is in agreement with the computational results. Electrochemical experiments show that iron is the redox active site in these complexes, performing a reversible one-electron oxidation. The four complexes are discussed with regard to their similarities and differences both to the [NiFe] hydrogenases and the C-cluster of Ni-containing CODH.
Investigation of the Effect of Some Optically Active Imine Compounds on the Enzyme Activities of hCA-I and hCA-II under In Vitro Conditions: An Experimental and Theoretical Study.

PubMed

Tektas, Osman; Akkemik, Ebru; Baykara, Haci

2016-06-01

Inhibitors of carbonic anhydrase (hCA; EC 4.2.1.1) are used as medicines for many diseases. Therefore, they are very important. In this study, a known series of Schiff bases were synthesized and their effects on the activities of hCA-I and hCA-II, which are cytosolic isoenzymes of carbonic anhydrase, were investigated under in vitro conditions. The synthesized compounds (H1, H2, H3, and H4) were found to cause inhibition on enzyme activities of hCA-1 and hCA-II. IC50 values of H1, H2, H3, and H4 compounds were 140, 88, 201, and 271 μM for hCA-I enzyme activity and 134, 251, 79, and 604 μM for hCA-II enzyme activity, respectively. The synthesized Schiff bases were characterized by several methods, including (1) H NMR, FT-IR, elemental analysis, and polarimetric measurements. Correlation coefficient square values (R(2) ) of comparison of the theoretical and experimental (1) H NMR shifts for H1, H2, H3, and H4 compounds were found as 0.9781, 0.9814, 0.9758, and 0.8635, respectively. © 2016 Wiley Periodicals, Inc.
Theoretical Study of Free Energy in Docking Stability of Azurin(II)-Cytochrome c551(II) Complex System

NASA Astrophysics Data System (ADS)

Yamamoto, Tetsunori; Nishikawa, Keigo; Sugiyama, Ayumu; Purqon, Acep; Mizukami, Taku; Shimahara, Hideto; Nagao, Hidemi; Nishikawa, Kiyoshi

2008-02-01

The docking structure of the Azurin-Cytochrome C551 is presented. We investigate a complex system of Azurin(II)-Cytochrome C551(II) by using molecular dynamics simulation. We estimate some physical properties, such as root-mean-square deviation (RMSD), binding energy between Azurin and Cytochrome C551, distance between Azurin(II) and Cytochrome C551(II) through center of mass and each active site. We also discuss docking stability in relation to the configuration by free energy between Azurin(II)-Cytochrome C551(II) and Azurin(I)-Cytochrome C551(III).
Persistent oxidative stress following renal ischemia-reperfusion injury increases ANG II hemodynamic and fibrotic activity

PubMed Central

Leonard, Ellen C.; Beal, Alisa G.; Schleuter, Devin; Friedrich, Jessica

2012-01-01

ANG II is a potent renal vasoconstrictor and profibrotic factor and its activity is enhanced by oxidative stress. We sought to determine whether renal oxidative stress was persistent following recovery from acute kidney injury (AKI) induced by ischemia-reperfusion (I/R) injury in rats and whether this resulted in increased ANG II sensitivity. Rats were allowed to recover from bilateral renal I/R injury for 5 wk and renal blood flow responses were measured. Post-AKI rats showed significantly enhanced renal vasoconstrictor responses to ANG II relative to sham-operated controls and treatment of AKI rats with apocynin (15 mM, in the drinking water) normalized these responses. Recovery from AKI for 5 wk resulted in sustained oxidant stress as indicated by increased dihydroethidium incorporation in renal tissue slices and was normalized in apocynin-treated rats. Surprisingly, the renal mRNA expression for common NADPH oxidase subunits was not altered in kidneys following recovery from AKI; however, mRNA screening using PCR arrays suggested that post-AKI rats had decreased renal Gpx3 mRNA and an increased expression other prooxidant genes such as lactoperoxidase, myeloperoxidase, and dual oxidase-1. When rats were infused for 7 days with ANG II (100 ng·kg−1·min−1), renal fibrosis was not apparent in sham-operated control rats, but it was enhanced in post-AKI rats. The profibrotic response was significantly attenuated in rats treated with apocynin. These data suggest that there is sustained renal oxidant stress following recovery from AKI that alters both renal hemodynamic and fibrotic responses to ANG II, and may contribute to the transition to chronic kidney disease following AKI. PMID:22442209
Endothelial monocyte activating polypeptide-II modulates endothelial cell responses by degrading hypoxia-inducible factor-1alpha through interaction with PSMA7, a component of the proteasome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tandle, Anita T.; Calvani, Maura; Uranchimeg, Badarch

The majority of human tumors are angiogenesis dependent. Understanding the specific mechanisms that contribute to angiogenesis may offer the best approach to develop therapies to inhibit angiogenesis in cancer. Endothelial monocyte activating polypeptide-II (EMAP-II) is an anti-angiogenic cytokine with potent effects on endothelial cells (ECs). It inhibits EC proliferation and cord formation, and it suppresses primary and metastatic tumor growth in-vivo. However, very little is known about the molecular mechanisms behind the anti-angiogenic activity of EMAP-II. In the present study, we explored the molecular mechanism behind the anti-angiogenic activity exerted by this protein on ECs. Our results demonstrate that EMAP-IImore » binds to the cell surface {alpha}5{beta}1 integrin receptor. The cell surface binding of EMAP-II results in its internalization into the cytoplasmic compartment where it interacts with its cytoplasmic partner PSMA7, a component of the proteasome degradation pathway. This interaction increases hypoxia-inducible factor 1-alpha (HIF-1{alpha}) degradation under hypoxic conditions. The degradation results in the inhibition of HIF-1{alpha} mediated transcriptional activity as well as HIF-1{alpha} mediated angiogenic sprouting of ECs. HIF-1{alpha} plays a critical role in angiogenesis by activating a variety of angiogenic growth factors. Our results suggest that one of the major anti-angiogenic functions of EMAP-II is exerted through its inhibition of the HIF-1{alpha} activities.« less
Quality assessment of osteoporosis clinical practice guidelines for physical activity and safe movement: an AGREE II appraisal.

PubMed

Armstrong, James Jacob; Rodrigues, Isabel Braganca; Wasiuta, Tom; MacDermid, Joy C

2016-01-01

Many osteoporosis clinical practice guidelines are published, and the extent to which physical activity and safe movement is addressed varies. To better inform clinical decision-making, a quality assessment and structured analysis of recommendations was undertaken. Guideline quality varied substantially, and improvement is necessary in physical activity and safe movement recommendations. The purpose of the present study is to survey available osteoporosis clinical practice guidelines (CPGs) containing physical activity and safe movement recommendations in order to assess the methodological quality with which they were developed. An analysis of the various physical activity and safe movement recommendations was conducted to determine variability between CPGs. An online literature search revealed 19 CPGs meeting our inclusion criteria. Three independent scorers evaluated CPG quality using the Appraisal of Guidelines for Research and Evaluation version II (AGREE II) instrument. Two separate individuals used a standard table to extract relevant recommendations. Intra-reviewer AGREE II score agreement ranged from fair to good (intra-class correlation coefficient (ICC) = 0.34 to 0.65). The quality of the 19 included CPGs was variable (AGREE sub-scores: 14 to 100%). CPGs scored higher in the "scope and purpose" and "clarity of presentation" domains. They scored the lowest in "applicability" and "editorial independence." Four CPGs were classified as high quality, ten average quality, and five low quality. Most CPGs recommended weight-bearing, muscle-strengthening, and resistance exercises. Information on exercise dosage, progression, and contraindications was often absent. Immobility and movements involving spinal flexion and/or torsion were discouraged. There were several high-quality CPGs; however, variability in quality and lack of specific parameters for implementation necessitates caution and critical examination by readers. CPG development groups should pay
Stellar rotation periods determined from simultaneously measured Ca II H&K and Ca II IRT lines

NASA Astrophysics Data System (ADS)

Mittag, M.; Hempelmann, A.; Schmitt, J. H. M. M.; Fuhrmeister, B.; González-Pérez, J. N.; Schröder, K.-P.

2017-11-01

Aims: Previous studies have shown that, for late-type stars, activity indicators derived from the Ca II infrared-triplet (IRT) lines are correlated with the indicators derived from the Ca II H&K lines. Therefore, the Ca II IRT lines are in principle usable for activity studies, but they may be less sensitive when measuring the rotation period. Our goal is to determine whether the Ca II IRT lines are sufficiently sensitive to measure rotation periods and how any Ca II IRT derived rotation periods compare with periods derived from the "classical" Mount Wilson S-index. Methods: To analyse the Ca II IRT lines' sensitivity and to measure rotation periods, we define an activity index for each of the Ca II IRT lines similar to the Mount Wilson S-index and perform a period analysis for the lines separately and jointly. Results: For eleven late-type stars we can measure the rotation periods using the Ca II IRT indices similar to those found in the Mount Wilson S-index time series and find that a period derived from all four indices gives the most probable rotation period; we find good agreement for stars with already existing literature values. In a few cases the computed periodograms show a complicated structure with multiple peaks, meaning that formally different periods are derived in different indices. We show that in one case, this is due to data sampling effects and argue that denser cadence sampling is necessary to provide credible evidence for differential rotation. However, our TIGRE data for HD 101501 shows good evidence for the presence of differential rotation.
SphK1 inhibitor II (SKI-II) inhibits acute myelogenous leukemia cell growth in vitro and in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Li; Weng, Wei; Sun, Zhi-Xin

Previous studies have identified sphingosine kinase 1 (SphK1) as a potential drug target for treatment of acute myeloid leukemia (AML). In the current study, we investigated the potential anti-leukemic activity of a novel and specific SphK1 inhibitor, SKI-II. We demonstrated that SKI-II inhibited growth and survival of human AML cell lines (HL-60 and U937 cells). SKI-II was more efficient than two known SphK1 inhibitors SK1-I and FTY720 in inhibiting AML cells. Meanwhile, it induced dramatic apoptosis in above AML cells, and the cytotoxicity by SKI-II was almost reversed by the general caspase inhibitor z-VAD-fmk. SKI-II treatment inhibited SphK1 activation, andmore » concomitantly increased level of sphingosine-1-phosphate (S1P) precursor ceramide in AML cells. Conversely, exogenously-added S1P protected against SKI-II-induced cytotoxicity, while cell permeable short-chain ceramide (C6) aggravated SKI-II's lethality against AML cells. Notably, SKI-II induced potent apoptotic death in primary human AML cells, but was generally safe to the human peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. In vivo, SKI-II administration suppressed growth of U937 leukemic xenograft tumors in severe combined immunodeficient (SCID) mice. These results suggest that SKI-II might be further investigated as a promising anti-AML agent. - Highlights: • SKI-II inhibits proliferation and survival of primary and transformed AML cells. • SKI-II induces apoptotic death of AML cells, but is safe to normal PBMCs. • SKI-II is more efficient than two known SphK1 inhibitors in inhibiting AML cells. • SKI-II inhibits SphK1 activity, while increasing ceramide production in AML cells. • SKI-II dose-dependently inhibits U937 xenograft growth in SCID mice.« less
HTLV-I and HTLV-II Tax: differences in induction of micronuclei in cells and transcriptional activation of viral LTRs.

PubMed

Semmes, O J; Majone, F; Cantemir, C; Turchetto, L; Hjelle, B; Jeang, K T

1996-03-01

Human T-cell leukemia virus (HTLV) types I and II are highly related viruses that differ in disease manifestations. HTLV-I has been linked unmistakably to adult T-cell leukemia-lymphoma. On the other hand, there is little evidence that prior infection with HTLV-II increases risk for lymphoproliferative disorders. Both viruses encode homologous transcriptional-activating proteins (respectively designated as Tax1 and Tax2) which have been suggested to be important mediators of viral pathogenesis. Previously, we reported that Tax1 is a potent inducer of micronuclei formation in cells. Here, we present evidence that Tax2 lacks micronuclei inductive ability. We contrast this phenotypic difference between Tax1 and Tax2 at the cellular level with their similarities at the molecular level in transcriptional activation.
Role of oxidants in enhancing dewaterability of anaerobically digested sludge through Fe (II) activated oxidation processes: hydrogen peroxide versus persulfate

PubMed Central

Song, Kang; Zhou, Xu; Liu, Yiqi; Gong, Yanyan; Zhou, Beibei; Wang, Dongbo; Wang, Qilin

2016-01-01

Improving dewaterability of sludge is important for the disposal of sludge in wastewater treatment plants (WWTPs). This study, for the first time, investigated the Fe(II) activated oxidization processes in improving anaerobically digested sludge (ADS) dewaterability. The combination of Fe(II) (0–100 mg/g total solids (TS)) and persulfate (0–1,000 mg/g TS) under neutral pH as well as the combination of Fe(II) (0–100 mg/g TS) and hydrogen peroxide (HP) (0–1,000 mg/g TS) under pH 3.0 were used to examine and compare their effect on the ADS dewaterability enhancement. The highest ADS dewaterability enhancement was attained at 25 mg Fe(II)/g TS and 50 mg HP/g TS, when the CST (CST: the capillary suction time, a sludge dewaterability indicator) was reduced by 95%. In contrast, the highest CST reduction in Fe(II)-persulfate conditioning was 90%, which was obtained at 50 mg Fe(II)/g TS and 250 mg persulfate/g TS. The results showed that Fe(II)-HP conditioning was comparable with Fe(II)-persulfate conditioning in terms of highest CST reduction. Economic analysis suggested that the Fe(II)-HP conditioning was more promising for improving ADS dewaterability compared with Fe(II)-persulfate conditioning, with the saving being up to $65,000 per year in a WWTP with a population equivalent of 100,000. PMID:27109500
Active background suppression with the liquid argon scintillation veto of GERDA Phase II

NASA Astrophysics Data System (ADS)

Agostini, M.; Allardt, M.; Bakalyarov, A. M.; Balata, M.; Barabanov, I.; Baudis, L.; Bauer, C.; Bellotti, E.; Belogurov, S.; Belyaev, S. T.; Benato, G.; Bettini, A.; Bezrukov, L.; Bode, T.; Borowicz, D.; Brudanin, V.; Brugnera, R.; Caldwell, A.; Cattadori, C.; Chernogorov, A.; D'Andrea, V.; Demidova, E. V.; Di Marco, N.; Domula, A.; Doroshkevich, E.; Egorov, V.; Falkenstein, R.; Frodyma, N.; Gangapshev, A.; Garfagnini, A.; Gooch, C.; Grabmayr, P.; Gurentsov, V.; Gusev, K.; Hakenmüller, J.; Hegai, A.; Heisel, M.; Hemmer, S.; Hofmann, W.; Hult, M.; Inzhechik, L. V.; Janicskó Csáthy, J.; Jochum, J.; Junker, M.; Kazalov, V.; Kihm, T.; Kirpichnikov, I. V.; Kirsch, A.; Kish, A.; Klimenko, A.; Kneißl, R.; Knöpfle, K. T.; Kochetov, O.; Kornoukhov, V. N.; Kuzminov, V. V.; Laubenstein, M.; Lazzaro, A.; Lebedev, V. I.; Lehnert, B.; Liao, H. Y.; Lindner, M.; Lippi, I.; Lubashevskiy, A.; Lubsandorzhiev, B.; Lutter, G.; Macolino, C.; Majorovits, B.; Maneschg, W.; Medinaceli, E.; Miloradovic, M.; Mingazheva, R.; Misiaszek, M.; Moseev, P.; Nemchenok, I.; Palioselitis, D.; Panas, K.; Pandola, L.; Pelczar, K.; Pullia, A.; Riboldi, S.; Rumyantseva, N.; Sada, C.; Salamida, F.; Salathe, M.; Schmitt, C.; Schneider, B.; Schönert, S.; Schreiner, J.; Schulz, O.; Schütz, A.-K.; Schwingenheuer, B.; Selivanenko, O.; Shevzik, E.; Shirchenko, M.; Simgen, H.; Smolnikov, A.; Stanco, L.; Vanhoefer, L.; Vasenko, A. A.; Veresnikova, A.; von Sturm, K.; Wagner, V.; Wegmann, A.; Wester, T.; Wiesinger, C.; Wojcik, M.; Yanovich, E.; Zhitnikov, I.; Zhukov, S. V.; Zinatulina, D.; Zuber, K.; Zuzel, G.

2017-09-01

The observation of neutrinoless double beta decay would allow to shed light onto the particle nature of neutrinos. Gerda is aiming to perform a background-free search for this process using high purity germanium detectors enriched in 76Ge operated in liquid argon. This goal relies on the application of active background suppression techniques. A low background light instrumentation has been installed for Phase II to detect events with coincident energy deposition in the nearby liquid argon. The intended background index of ˜10-3 cts/(keV·ky·yr) has been confirmed.
Discovery of a Series of Imidazo[4,5-b]pyridines with Dual Activity at Angiotensin II Type 1 Receptor and Peroxisome Proliferator-Activated Receptor-[gamma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Casimiro-Garcia, Agustin; Filzen, Gary F.; Flynn, Declan

2013-03-07

Mining of an in-house collection of angiotensin II type 1 receptor antagonists to identify compounds with activity at the peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) revealed a new series of imidazo[4,5-b]pyridines 2 possessing activity at these two receptors. Early availability of the crystal structure of the lead compound 2a bound to the ligand binding domain of human PPAR{gamma} confirmed the mode of interaction of this scaffold to the nuclear receptor and assisted in the optimization of PPAR{gamma} activity. Among the new compounds, (S)-3-(5-(2-(1H-tetrazol-5-yl)phenyl)-2,3-dihydro-1H-inden-1-yl)-2-ethyl-5-isobutyl-7-methyl-3H-imidazo[4,5-b]pyridine (2l) was identified as a potent angiotensin II type I receptor blocker (IC{sub 50} = 1.6 nM) with partialmore » PPAR{gamma} agonism (EC{sub 50} = 212 nM, 31% max) and oral bioavailability in rat. The dual pharmacology of 2l was demonstrated in animal models of hypertension (SHR) and insulin resistance (ZDF rat). In the SHR, 2l was highly efficacious in lowering blood pressure, while robust lowering of glucose and triglycerides was observed in the male ZDF rat.« less
Controls on Fe(II)-Activated Trace Element Release from Goethite and Hematite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frierdich, Andrew J.; Catalano, Jeffrey G.

2012-03-26

Electron transfer and atom exchange (ETAE) between aqueous Fe(II) and Fe(III) oxides induces surface growth and dissolution that affects trace element fate and transport. We have recently demonstrated Ni(II) cycling through goethite and hematite (adsorbed Ni incorporates into the mineral structure and preincorporated Ni releases to solution) during Fe(II)-Fe(III) ETAE. However, the chemical parameters affecting net trace element release remain unknown. Here, we examine the chemical controls on Ni(II) and Zn(II) release from Ni- and Zn-substituted goethite and hematite during reaction with Fe(II). Release follows a rate law consistent with surface reaction limited mineral dissolution and suggests that release occursmore » near sites of Fe(III) reductive dissolution during Fe(II)-Fe(III) ETAE. Metal substituent type affects reactivity; Zn release is more pronounced from hematite than goethite, whereas the opposite trend occurs for Ni. Buildup of Ni or Zn in solution inhibits further release but this resumes upon fluid exchange, suggesting that sustained release is possible under flow conditions. Mineral and aqueous Fe(II) concentrations as well as pH strongly affect sorbed Fe(II) concentrations, which directly control the reaction rates and final metal concentrations. Our results demonstrate that structurally incorporated trace elements are mobilized from iron oxides into fluids without abiotic or microbial net iron reduction. Such release may affect micronutrient availability, contaminant transport, and the distribution of redox-inactive trace elements in natural and engineered systems.« less
A monofunctional platinum(II)-based anticancer agent from a salicylanilide derivative: Synthesis, antiproliferative activity, and transcription inhibition.

PubMed

Wang, Beilei; Wang, Zhigang; Ai, Fujin; Tang, Wai Kin; Zhu, Guangyu

2015-01-01

Cationic monofunctional platinum(II)-based anticancer agents with a general formula of cis-[Pt(NH3)2(N-donor)Cl](+) have recently drawn significant attention due to their unique mode of action, distinctive anticancer spectrum, and promising antitumor activity both in vitro and in vivo. Understanding the mechanism of action of novel monofunctional platinum compounds through rational drug design will aid in the further development of active agents. In this study, we synthesized and evaluated a monofunctional platinum-based anticancer agent SA-Pt containing a bulky salicylanilide moiety. The antiproliferative activity of SA-Pt was close to that of cisplatin. Mechanism studies revealed that SA-Pt entered HeLa cells more efficiently than cisplatin, blocked the cell cycle at the S-phase, and induced apoptosis. The compound bound to DNA as effectively as cisplatin, but did not block RNA polymerase II-mediated transcription as strongly as cisplatin, indicating that once the compound formed Pt-DNA lesions, the salicylanilide group was more easily recognized and removed. This study not only enriches the family of monofunctional platinum-based anticancer agents but also guides the design of more potent monofunctional platinum complexes. Copyright © 2014 Elsevier Inc. All rights reserved.
Mesoporous silica nanoparticles supported copper(II) and nickel(II) Schiff base complexes: Synthesis, characterization, antibacterial activity and enzyme immobilization

NASA Astrophysics Data System (ADS)

Tahmasbi, Leila; Sedaghat, Tahereh; Motamedi, Hossein; Kooti, Mohammad

2018-02-01

Mesoporous silica nanoparticles (MSNs) were prepared by sol-gel method and functionalized with 3-aminopropyltriethoxysilane. Schiff base grafted mesoporous silica nanoparticle was synthesized by the condensation of 2-hydroxy-3-methoxybenzaldehyde and amine-functionalized MSNs. The latter material was then treated with Cu(II) and Ni(II) salts separately to obtain copper and nickel complexes anchored mesoporous composites. The newly prepared hybrid organic-inorganic nanocomposites have been characterized by several techniques such as FT-IR, LA-XRD, FE-SEM, TEM, EDS, BET and TGA. The results showed all samples have MCM-41 type ordered mesoporous structure and functionalization occurs mainly inside the mesopore channel. The presence of all elements in synthesized nanocomposites and the coordination of Schiff base via imine nitrogen and phenolate oxygen were confirmed. MSNs and all functionalized MSNs have uniform spherical nanoparticles with a mean diameter less than 100 nm. The as-synthesized mesoporous nanocomposites were investigated for antibacterial activity against Gram-positive (B. subtilis and S. aureus) and Gram-negative (E. coli and P. aeruginosa) bacteria, as carrier for gentamicin and also for immobilization of DNase, coagulase and amylase enzymes. MSN-SB-Ni indicated bacteriocidal effect against S.aureus and all compounds were found to be good carrier for gentamicin. Results of enzyme immobilization for DNase and coagulase and α-amylase revealed that supported metal complexes efficiently immobilized enzymes.
Activity measurements of the radionuclides 18F and 64Cu for the NIST, USA in the ongoing comparisons BIPM.RI(II)-K4.F-18 and BIPM.RI(II)-K4.Cu-64

NASA Astrophysics Data System (ADS)

Michotte, C.; Nonis, M.; Bergeron, D.; Cessna, J.; Fitzgerald, R.; Pibida, L.; Zimmerman, B.; Fenwick, A.; Ferreira, K.; Keightley, J.; Da Silva, I.

2017-01-01

In 2016, comparisons of activity measurements of 18F and 64Cu using the Transfer Instrument of the International Reference System (SIRTI) took place at the National Institute of Standards and Technology (NIST, USA). This is the first SIRTI comparison for 64Cu. Ampoules containing about 27 kBq of 18F and 100 kBq of 64Cu solutions were measured in the SIRTI for about 5 and 1.5 half-lives, respectively. The NIST standardized the activity in the ampoules by ionization chamber measurements traceable to 4π(LS)β-γ anticoincidence measurements. The comparisons, identifiers BIPM.RI(II)-K4.F-18 and BIPM.RI(II)-K4.Cu-64, are linked to the corresponding BIPM.RI(II)-K1.F-18 and BIPM.RI(II)-K1.Cu-64 comparisons and degrees of equivalence with the respective key comparison reference values have been evaluated. The NIST replaces its earlier degree of equivalence for 18F obtained in the frame of the CCRI(II)-K3.F-18 comparison in 2001. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Synthesis, characterization, redox behavior, DNA and protein binding and antibacterial activity studies of ruthenium(II) complexes of bidentate schiff bases.

PubMed

Paul, Hena; Sen, Buddhadeb; Mondal, Tapan Kumar; Chattopadhyay, Pabitra

2017-08-03

Two new ruthenium(II) complexes of Schiff base ligands (L) derived from cinnamaldehyde and ethylenediamine formulated as [Ru(L)(bpy) 2 ](ClO 4 ) 2 , where L 1 = N,N'-bis(4-nitrocinnamald-ehyde)ethylenediamine and L 2 = N,N'-bis(2-nitrocinnamaldehyde)-ethylenediamine for complex 1 and 2, respectively, were isolated in pure form. The complexes were characterized by physicochemical and spectroscopic methods. The electrochemical behavior of the complexes showed the Ru(III)/Ru(II) couple at different potentials with quasi-reversible voltammograms. The interaction of the complexes with calf thymus DNA (CT-DNA) using absorption, emission spectral studies and electrochemical techniques have been used to determine the binding constant, K b and the linear Stern-Volmer quenching constant, K SV . The results indicate that the ruthenium(II) complexes interact with CT-DNA strongly in a groove binding mode. The interactions of bovine serum albumin (BSA) with the complexes were also investigated with the help of absorption and fluorescence spectroscopy tools. Absorption spectroscopy proved the formation of a ground state BSA-[Ru(L)(bpy) 2 ](ClO 4 ) 2 complex. The antibacterial study showed that the Ru(II) complexes (1 and 2) have better activity than the standard antibiotics but weak activity than the ligands.
New tailored substituted benzothiazole Schiff base Cu(II)/Zn(II) antitumor drug entities: effect of substituents on DNA binding profile, antimicrobial and cytotoxic activity.

PubMed

Zehra, Siffeen; Shavez Khan, Mohammad; Ahmad, Iqbal; Arjmand, Farukh

2018-05-07

New tailored Cu(II) & Zn(II) metal-based antitumor drug entities were synthesized from substituted benzothiazole o‒vanillin Schiff base ligands. The complexes were thoroughly characterized by elemental analysis, spectroscopic studies {IR, 1 H & 13 C NMR, ESI-MS, EPR} and magnetic susceptibility measurements. The structure activity relationship (SAR) studies of benzothiazole Cu(II) & Zn(II) complexes having molecular formulas [C 30 H 22 CuN 5 O 7 S 2 ], [C 30 H 20 Cl 2 CuN 5 O 7 S 2 ], [C 30 H 20 CuF 2 N 5 O 7 S 2 ], [C 30 H 22 N 4 O 4 S 2 Zn], [C 30 H 20 Cl 2 N 4 O 4 S 2 Zn], and [C 30 H 20 F 2 N 5 O 7 S 2 Zn], with CT‒DNA were performed by employing absorption, emission titrations, and hydrodynamic measurements. The DNA binding affinity was quantified by K b and K sv values which gave higher binding propensity for chloro-substituted Cu(II) [C 30 H 20 Cl 2 CuN 5 O 7 S 2 ] complex, suggestive of groove binding mode with subtle partial intercalation. Molecular properties and drug likeness profile were assessed for the ligands and all the Lipinski's rules were found to be obeyed. The antimicrobial potential of ligands and their Cu(II) & Zn(II) complexes were screened against some notably important pathogens viz., E. coli, S. aureus, P. aeruginosa, B. subtilis, and C. albicans. The cytotoxicity of the complexes [C 30 H 20 Cl 2 CuN 5 O 7 S 2 ], [C 30 H 20 CuF 2 N 5 O 7 S 2 ], [C 30 H 20 Cl 2 N 4 O 4 S 2 Zn], and [C 30 H 20 F 2 N 5 O 7 S 2 Zn] were evaluated against five human cancer cell lines viz., MCF‒7 (breast), MIA‒PA‒CA‒2 (pancreatic), HeLa (cervix) and Hep‒G2 (Hepatoma) and A498 (Kidney) by SRB assay which revealed that chloro-substituted [C 30 H 20 Cl 2 CuN 5 O 7 S 2 ] complex, exhibited pronounced specific cytotoxicity with GI 50 value of 4.8 μg/ml against HeLa cell line. Molecular docking studies were also performed to explore the binding modes and orientation of the complexes in the DNA helix.

Photoregeneration of bovine rhodopsin from its signaling state.

PubMed

Arnis, S; Hofmann, K P

1995-07-25

In rhodopsin, 11-cis-retinal is bound by a protonated Schiff base and acts as a strong antagonist, which holds the receptor in its inactive ground state conformation. Light induces cis-/trans-retinal isomerization and a sequence of thermal transitions through intermediates. The active conformation that catalyzes GDP/GTP exchange in the G-protein (Gt) is generated from the metarhodopsin II intermediate (MII) and mediated by Schiff base proton translocation and proton uptake from the aqueous phase. In the stable nucleotide-free MII-Gt complex, any thermal transition of MII into other forms of rhodopsin is blocked. We have now studied how Gt affects flash-induced photochemical conversions of MII. Difference spectra from measured absorption changes show that MII photolyzes through two parallel pathways, with fast (1 ms) and slow (50 ms) kinetics (12 degrees C, pH 6). The slow pathway regenerates rhodopsin (9- or 11-cis) via Schiff base reprotonation and proton release. We infer a cis-isomerized early photoproduct (reverted meta, RM) preceding these thermal transitions. When MII is photolyzed in the MII-Gt complex, the slow absorption change is abolished, indicating that Gt blocks the completion of the regeneration process. This is due to the formation of a stable RM-Gt complex, as shown by successive photolysis of MII, RM, and ground state rhodopsin, and the application of GTP gamma S at different stages. The complex dissociates with GTP gamma S, and rhodopsin relaxes to the ground state. The results indicate that cis-retinal and Gt can bind to the receptor at the same time. We discuss the result that the protonations in the meta II state uncouple retinal geometry from Gt interaction.
Manganese(IV) Oxide Production by Acremonium sp. Strain KR21-2 and Extracellular Mn(II) Oxidase Activity

PubMed Central

Miyata, Naoyuki; Tani, Yukinori; Maruo, Kanako; Tsuno, Hiroshi; Sakata, Masahiro; Iwahori, Keisuke

2006-01-01

Ascomycetes that can deposit Mn(III, IV) oxides are widespread in aquatic and soil environments, yet the mechanism(s) involved in Mn oxide deposition remains unclear. A Mn(II)-oxidizing ascomycete, Acremonium sp. strain KR21-2, produced a Mn oxide phase with filamentous nanostructures. X-ray absorption near-edge structure (XANES) spectroscopy showed that the Mn phase was primarily Mn(IV). We purified to homogeneity a laccase-like enzyme with Mn(II) oxidase activity from cultures of strain KR21-2. The purified enzyme oxidized Mn(II) to yield suspended Mn particles; XANES spectra indicated that Mn(II) had been converted to Mn(IV). The pH optimum for Mn(II) oxidation was 7.0, and the apparent half-saturation constant was 0.20 mM. The enzyme oxidized ABTS [2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)] (pH optimum, 5.5; Km, 1.2 mM) and contained two copper atoms per molecule. Moreover, the N-terminal amino acid sequence (residues 3 to 25) was 61% identical with the corresponding sequence of an Acremonium polyphenol oxidase and 57% identical with that of a Myrothecium bilirubin oxidase. These results provide the first evidence that a fungal multicopper oxidase can convert Mn(II) to Mn(IV) oxide. The present study reinforces the notion of the contribution of multicopper oxidase to microbially mediated precipitation of Mn oxides and suggests that Acremonium sp. strain KR21-2 is a good model for understanding the oxidation of Mn in diverse ascomycetes. PMID:17021194
The activation threshold of CD4+ T cells is defined by TCR/peptide-MHC class II interactions in the thymic medulla.

PubMed

Stephen, Tom Li; Tikhonova, Anastasia; Riberdy, Janice M; Laufer, Terri M

2009-11-01

Immature thymocytes that are positively selected based upon their response to self-peptide-MHC complexes develop into mature T cells that are not overtly reactive to those same complexes. Developmental tuning is the active process through which TCR-associated signaling pathways of single-positive thymocytes are attenuated to respond appropriately to the peptide-MHC molecules that will be encountered in the periphery. In this study, we explore the mechanisms that regulate the tuning of CD4(+) single-positive T cells to MHC class II encountered in the thymic medulla. Experiments with murine BM chimeras demonstrate that tuning can be mediated by MHC class II expressed by either thymic medullary epithelial cells or thymic dendritic cells. Tuning does not require the engagement of CD4 by MHC class II on stromal cells. Rather, it is mediated by interactions between MHC class II and the TCR. To understand the molecular changes that distinguish immature hyperactive T cells from tuned mature CD4(+) T cells, we compared their responses to TCR stimulation. The altered response of mature CD4 single-positive thymocytes is characterized by the inhibition of ERK activation by low-affinity self-ligands and increased expression of the inhibitory tyrosine phosphatase SHP-1. Thus, persistent TCR engagement by peptide-MHC class II on thymic medullary stroma inhibits reactivity to self-Ags and prevents autoreactivity in the mature repertoire.
O2 Activation and Double C-H Oxidation by a Mononuclear Manganese(II) Complex.

PubMed

Deville, Claire; Padamati, Sandeep K; Sundberg, Jonas; McKee, Vickie; Browne, Wesley R; McKenzie, Christine J

2016-01-11

A Mn(II) complex, [Mn(dpeo)2](2+) (dpeo=1,2-di(pyridin-2-yl)ethanone oxime), activates O2, with ensuing stepwise oxidation of the methylene group in the ligands providing an alkoxide and ultimately a ketone group. X-ray crystal-structure analysis of an intermediate homoleptic alkoxide Mn(III) complex shows tridentate binding of the ligand via the two pyridyl groups and the newly installed alkoxide moiety, with the oxime group no longer coordinated. The structure of a Mn(II) complex of the final ketone ligand, cis-[MnBr2(hidpe)2] (hidpe=2-(hydroxyimino)-1,2-di(pyridine-2-yl)ethanone) shows that bidentate oxime/pyridine coordination has been resumed. H2(18)O and (18)O2 labeling experiments suggest that the inserted O atoms originate from two different O2 molecules. The progress of the oxygenation was monitored through changes in the resonance-enhanced Raman bands of the oxime unit. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Rat leucine-rich protein binds and activates the promoter of the beta isoform of Ca2+/calmodulin-dependent protein kinase II gene.

PubMed

Ochiai, Nagahiro; Masumoto, Shuji; Sakagami, Hiroyuki; Yoshimura, Yoshiyuki; Yamauchi, Takashi

2007-05-01

We previously found the neuronal cell-type specific promoter and binding partner of the beta isoform of Ca(2+)/calmodulin-dependent protein kinase II (beta CaM kinase II) in rat brain [Donai, H., Morinaga, H., Yamauchi, T., 2001. Genomic organization and neuronal cell type specific promoter activity of beta isoform of Ca(2+)/calmodulin-dependent protein kinase II of rat brain. Mol. Brain Res. 94, 35-47]. In the present study, we purified a protein that binds specifically a promoter region of beta CaM kinase II gene from a nuclear extract of the rat cerebellum using DEAE-cellulose column chromatography, ammonium sulfate fractionation, gel filtration and polyacrylamide gel electrophoresis. The purified protein was identified as rat leucine-rich protein 157 (rLRP157) using tandem mass spectrometry. Then, we prepared its cDNA by reverse transcriptase-polymerase chain reaction (RT-PCR) from poly(A)(+)RNA of rat cerebellum. The rLRP157 cDNA was introduced into mouse neuroblastomaxrat glioma hybrid NG108-15 cells, and cells stably expressing rLRP157 (NG/LRP cells) were isolated. Binding of rLRP157 with the promoter sequence was confirmed by electrophoretic mobility shift assay using nuclear extract of NG/LRP cells. A luciferase reporter gene containing a promoter of beta CaM kinase II was transiently expressed in NG/LRP cells. Under the conditions, the promoter activity was enhanced about 2.6-fold in NG/LRP cells as compared with wild-type cells. The expression of rLRP157 mRNA was paralleled with that of beta CaM kinase II in the adult and embryo rat brain detected by in situ hybridization. Nuclear localization of rLRP157 was confirmed using GFP-rLRP157 fusion protein investigated under a confocal microscope. These results indicate that rLRP157 is one of the proteins binding to, and regulating the activity of, the promoter of beta CaM kinase II.
On-line separation and preconcentration of lead(II) by solid-phase extraction using activated carbon loaded with xylenol orange and its determination by flame atomic absorption spectrometry.

PubMed

Ensafi, Ali A; Shiraz, A Zendegi

2008-02-11

Activated carbon loaded with xylenol orange in a mini-column was used for the highly selective separation and preconcentration of Pb(II) ions. An on-line system for enrichment and the determination of Pb(II) was carried out on flame atomic absorption spectrometry. The conditions of preconcentration and quantitative recovery of Pb(II) from diluted solution, such as pH of aqueous phase, amount of the sorbent, volume of the solutions and flow variables were studied as well as effect of potential interfering ions. Under the optimum conditions, Pb(II) in an aqueous sample was concentrated about 200-fold and the detection limit was 0.4 ng mL(-1) Pb(II). The adsorption capacity of the solid phase was 0.20mg of lead per one gram of the modified activated carbon. The modified activated carbon is stable for several treatments of sample solutions without the need for using any chemical reagent. The recovery of lead(II) from river water, waste water, tap water, and in the following reference materials: SRM 2711 Montana soil and GBW-07605 tea were obtained in the range of 97-104% by the proposed method.
Biologically active and C-amidated hinnavinII-38-Asn produced from a Trx fusion construct in Escherichia coli.

PubMed

Kang, Chang Soo; Son, Seung-Yeol; Bang, In Seok

2008-12-01

The cabbage butterfly (Artogeia rapae) antimicrobial peptide hinnavinII as a member of cecropin family is synthesized as 37 residues in size with an amidated lysine at C-terminus and shows the humoral immune response to a bacterial invasion. In this work, a synthetic gene for hinnavinII-38-Asn (HIN) with an additional amino acid asparagine residue containing amide group at C-terminus was cloned into pET-32a(+) vector to allow expression of HIN as a Trx fusion protein in Escherichia coli strain BL21 (DE3) pLysS. The resulting expression level of the fusion protein Trx-HIN could reach 15-20% of the total cell proteins and more than 70% of the target proteins were in soluble form. The fusion protein could be purified successfully by HiTrap Chelating HP column and a high yield of 15 mg purified fusion protein was obtained from 80 ml E. coli culture. Recombinant HIN was readily obtained by enterokinase cleavage of the fusion protein followed by FPLC chromatography, and 3.18 mg pure active recombinant HIN was obtained from 80 ml culture. The molecular mass of recombinant HIN determined by MALDI-TOF mass spectrometer is 4252.084 Da which matches the theoretical mass (4252.0 Da) of HIN. Comparing the antimicrobial activities of the recombinant hinnavinII with C-amidated terminus to that without an amidated C-terminus, we found that the amide of asparagine at C-terminus of hinnavinII improved its potency on certain microorganism such as E. coli, Enterobacter cloacae, Bacillus megaterium, and Staphylococcus aureus.
Interaction of polyethyleneimine-anchored copper(II) complexes with tRNA studied by spectroscopy methods and biological activities.

PubMed

Lakshmipraba, Jagadeesan; Arunachalam, Sankaralingam; Gandi, Devadas A; Thirunalasundari, Thyagarajan; Vignesh, Sivanandham; James, Rathinam A

2017-05-01

Ultraviolet-visible, emission and circular dichroism spectroscopic methods were used in transfer RNA (tRNA) interaction studies performed for polyethyleneimine-copper(II) complexes [Cu(phen)(l-Tyr)BPEI]ClO 4 (where phen =1,10-phenanthroline, l-Tyr = l-tyrosine and BPEI = branched polyethyleneimine) with various degrees of coordination (x = 0.059, 0.149, 0.182) in the polymer chain. The results indicated that polyethyleneimine-copper(II) complexes bind with tRNA mostly through surface binding, although other binding modes, such as hydrogen bonding and van der Waals interactions, might also be present. Dye-exclusion, sulforhodamine B and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays of a polyethyleneimine-copper(II) complex with a higher degree of coordination against different cancer cell lines proved that the complex exhibited cytotoxic specificity and a significant cancer cell inhibition rate. Antimicrobial screening showed activity against some human pathogens. Copyright © 2016 John Wiley & Sons, Ltd.
An interactive human carbonic anhydrase-II (hCA-II) receptor--pharmacophore molecular model & anti-convulsant activity of the designed and synthesized 5-amino-1,3,4-thiadiazole-2-thiol conjugated imine derivatives.

PubMed

Yusuf, Mohammad; Khan, Riaz A; Khan, Maria; Ahmed, Bahar

2013-05-01

New imines, derived from aromatic aldehyde, chalcones and 5-amino-1,3,4-thiadiazole-2-thiol exhibited promising anti-convulsant activity which is explained through chemo-biological interactions at receptor site producing the inhibition of human Carbonic Anhydrase-II enzyme (hCA-II) through the proposed pharmacophore model at molecular levels as basis for pharmacological activity. The compounds 5-{1-(4-Chlorophenyl)-3-[4-(methoxy-phenyl)-prop-2-en-1-ylidene]amino}-1,3,4-thiadiazole-2-thiol (2b), 5-{[1-(4-chloro-phenyl)]-3-[4-(dimethyl-amino-phenyl)-prop-2-en-1-ylidene]amino}-1,3,4-thiadiazole-2-thiol (2c) and 5-{[1-(4-chloro-phenyl)]-3-[(4-amino-phenyl)-prop-2-en-1-ylidene]amino}-1,3,4-thiadiazole-2-thiol (2f) showed 100% activity in comparison with standard Acetazolamide, a known anti-convulsant drug. The compounds 2c, 2f also passed the Rotarod and Ethanol Potentiation tests which further confirmed them to be safe in motor coordination activity and safe from generating neurological toxicity. © 2013 John Wiley & Sons A/S.
Studies on the synthesis, spectra, catalytic and antibacterial activities of binuclear ruthenium(II) complexes.

PubMed

Krishnamoorthy, P; Sathyadevi, P; Deepa, K; Dharmaraj, N

2010-09-15

A new series of stable binuclear ruthenium(II) carbonyl complexes of the general formula [{RuX(CO)(EPh(3))(2)}(2)L] (where X=H or Cl; E=P or As and L=dibasic tetradentate diacetyl resorcinol (H(2)-DAR)) have been synthesised by reacting ruthenium(II) starting complexes [RuHX(CO)(EPh(3))(3)] (where X=H or Cl; E=P or As) and 4,6-diacetylresorcinol (H(2)-DAR) ligand in benzene medium. The structure of the new binuclear ruthenium(II) carbonyl complexes was established using elemental analysis, spectra (FT-IR, UV-vis and (1)H NMR), electrochemical and thermal studies. In these reactions, the 4,6-diacetylresorcinol (H(2)-DAR) ligand behaves as a binegative tetradentate chelating ligand coordinating through O,O atoms of both the carbonyl and phenolic C-O groups by replacing a molecule of PPh(3)/AsPh(3) and a hydride ion from the starting complexes. Further, all these complexes were also employed as new catalysts for the oxidation of primary and secondary alcohols in the presence of N-methylmorpholine-N-oxide (NMO) as a more viable co-oxidant. The free ligand and their metal complexes have also been screened for their antibacterial activity against the growth of gram +ve and gram -ve bacterial cultures. Copyright 2010 Elsevier B.V. All rights reserved.
Positive correlation between blood pressure or heart rate and chymase-dependent angiotensin II-forming activity in circulating mononuclear leukocytes measured by new ELISA.

PubMed

Okamura, Keisuke; Okuda, Tetsu; Shirai, Kazuyuki; Urata, Hidenori

2018-01-01

The aim of the present study was to establish a convenient clinically applicable assay method for chymase-dependent angiotensin II forming activity of circulating mononuclear leukocytes (CML), which was potentially a marker of tissue chymase activity. Using this method, association between CML chymase activity and clinical parameters was determined. Cardiovascular outpatients (n = 170) without taking antihypertensive medication were recruited. An ELISA for chymase-dependent angiotensin II-forming activity in CML was established using Nma /Dnp-modified angiotensin I. Logistic regression analysis revealed that age and male gender were significant independent determinants of the increased CML chymase activity. After adjustment by age and gender, the CML chymase activity was positively correlated with systolic blood pressure, pulse rate, and the brain natriuretic peptide level. The relation between blood pressure and CML chymase activity suggests that it might reflect that increased tissue chymase activity contributes to systemic high blood pressure and heart rate because plasma chymase is inactive due to inhibitory plasma inhibitors.
Synthesis and spectral characterization of Schiff base complexes of Cu(II), Co(II), Zn(II) and VO(IV) containing 4-(4-aminophenyl)morpholine derivatives: Antimicrobial evaluation and anticancer studies

NASA Astrophysics Data System (ADS)

Dhahagani, K.; Mathan Kumar, S.; Chakkaravarthi, G.; Anitha, K.; Rajesh, J.; Ramu, A.; Rajagopal, G.

2014-01-01

Metal(II) chelates of Schiff bases derived from the condensation of 4-morpholinoaniline with substituted salicylaldehyde have been prepared and characterized by 1H NMR, IR, electronic, EPR, and magnetic measurement studies. The complexes are of the type M(X-MPMP)2 [where M = Cu(II), Co(II)), Zn(II), or VO(IV); MPMP = 2-[(4 morpholinophenyl imino) methyl] 4-X-phenol, X = Cl, (L1H), X = Br (L2H)]. Single crystal X-ray crystallography studies confirm the structure of newly synthesized Schiff bases. The Schiff bases act as bidentate monobasic ligands, coordinating through deprotonated phenolic oxygen and azomethine nitrogen atoms. The free ligands and metal complexes are screened for their biopotency. Metal complexes exhibit better activity than ligands. Anticancer activity of ligands and their metal complexes are evaluated in human heptocarcinoma(HepG2) cells. The preliminary bioassay indicates that the Schiff base and its zinc complex exhibit inhibitory activity against the human gastric cancer cell lines.
Concurrent hippocampal induction of MHC II pathway components and glial activation with advanced aging is not correlated with cognitive impairment.

PubMed

VanGuilder, Heather D; Bixler, Georgina V; Brucklacher, Robert M; Farley, Julie A; Yan, Han; Warrington, Junie P; Sonntag, William E; Freeman, Willard M

2011-10-11

Age-related cognitive dysfunction, including impairment of hippocampus-dependent spatial learning and memory, affects approximately half of the aged population. Induction of a variety of neuroinflammatory measures has been reported with brain aging but the relationship between neuroinflammation and cognitive decline with non-neurodegenerative, normative aging remains largely unexplored. This study sought to comprehensively investigate expression of the MHC II immune response pathway and glial activation in the hippocampus in the context of both aging and age-related cognitive decline. Three independent cohorts of adult (12-13 months) and aged (26-28 months) F344xBN rats were behaviorally characterized by Morris water maze testing. Expression of MHC II pathway-associated genes identified by transcriptomic analysis as upregulated with advanced aging was quantified by qPCR in synaptosomal fractions derived from whole hippocampus and in hippocampal subregion dissections (CA1, CA3, and DG). Activation of astrocytes and microglia was assessed by GFAP and Iba1 protein expression, and by immunohistochemical visualization of GFAP and both CD74 (Ox6) and Iba1. We report a marked age-related induction of neuroinflammatory signaling transcripts (i.e., MHC II components, toll-like receptors, complement, and downstream signaling factors) throughout the hippocampus in all aged rats regardless of cognitive status. Astrocyte and microglial activation was evident in CA1, CA3 and DG of intact and impaired aged rat groups, in the absence of differences in total numbers of GFAP+ astrocytes or Iba1+ microglia. Both mild and moderate microglial activation was significantly increased in all three hippocampal subregions in aged cognitively intact and cognitively impaired rats compared to adults. Neither induction of MHCII pathway gene expression nor glial activation correlated to cognitive performance. These data demonstrate a novel, coordinated age-related induction of the MHC II immune
Regulation of the Proteasome by Neuronal Activity and Calcium/Calmodulin-dependent Protein Kinase II*

PubMed Central

Djakovic, Stevan N.; Schwarz, Lindsay A.; Barylko, Barbara; DeMartino, George N.; Patrick, Gentry N.

2009-01-01

Protein degradation via the ubiquitin proteasome system has been shown to regulate changes in synaptic strength that underlie multiple forms of synaptic plasticity. It is plausible, therefore, that the ubiquitin proteasome system is itself regulated by synaptic activity. By utilizing live-cell imaging strategies we report the rapid and dynamic regulation of the proteasome in hippocampal neurons by synaptic activity. We find that the blockade of action potentials (APs) with tetrodotoxin inhibited the activity of the proteasome, whereas the up-regulation of APs with bicuculline dramatically increased the activity of the proteasome. In addition, the regulation of the proteasome is dependent upon external calcium entry in part through N-methyl-d-aspartate receptors and L-type voltage-gated calcium channels and requires the activity of calcium/calmodulin-dependent protein kinase II (CaMKII). Using in vitro and in vivo assays we find that CaMKII stimulates proteasome activity and directly phosphorylates Rpt6, a subunit of the 19 S (PA700) subcomplex of the 26 S proteasome. Our data provide a novel mechanism whereby CaMKII may regulate the proteasome in neurons to facilitate remodeling of synaptic connections through protein degradation. PMID:19638347
Regulation of the proteasome by neuronal activity and calcium/calmodulin-dependent protein kinase II.

PubMed

Djakovic, Stevan N; Schwarz, Lindsay A; Barylko, Barbara; DeMartino, George N; Patrick, Gentry N

2009-09-25

Protein degradation via the ubiquitin proteasome system has been shown to regulate changes in synaptic strength that underlie multiple forms of synaptic plasticity. It is plausible, therefore, that the ubiquitin proteasome system is itself regulated by synaptic activity. By utilizing live-cell imaging strategies we report the rapid and dynamic regulation of the proteasome in hippocampal neurons by synaptic activity. We find that the blockade of action potentials (APs) with tetrodotoxin inhibited the activity of the proteasome, whereas the up-regulation of APs with bicuculline dramatically increased the activity of the proteasome. In addition, the regulation of the proteasome is dependent upon external calcium entry in part through N-methyl-D-aspartate receptors and L-type voltage-gated calcium channels and requires the activity of calcium/calmodulin-dependent protein kinase II (CaMKII). Using in vitro and in vivo assays we find that CaMKII stimulates proteasome activity and directly phosphorylates Rpt6, a subunit of the 19 S (PA700) subcomplex of the 26 S proteasome. Our data provide a novel mechanism whereby CaMKII may regulate the proteasome in neurons to facilitate remodeling of synaptic connections through protein degradation.
H- ras deletion protects against angiotensin II-induced arterial hypertension and cardiac remodeling through protein kinase G-Iβ pathway activation.

PubMed

Martín-Sánchez, Paloma; Luengo, Alicia; Griera, Mercedes; Orea, María Jesús; López-Olañeta, Marina; Chiloeches, Antonio; Lara-Pezzi, Enrique; de Frutos, Sergio; Rodríguez-Puyol, Manuel; Calleros, Laura; Rodríguez-Puyol, Diego

2018-02-01

Ras proteins regulate cell survival, growth, differentiation, blood pressure, and fibrosis in some organs. We have demonstrated that H- ras gene deletion produces mice hypotension via a soluble guanylate cyclase-protein kinase G (PKG)-dependent mechanism. In this study, we analyzed the consequences of H- ras deletion on cardiac remodeling induced by continuous angiotensin II (AngII) infusion and the molecular mechanisms implied. Left ventricular posterior wall thickness and mass and cardiomyocyte cross-sectional area were similar between AngII-treated H-Ras knockout (H -ras -/- ) and control wild-type (H -ras +/+ ) mice, as were extracellular matrix protein expression. Increased cardiac PKG-Iβ protein expression in H -ras -/- mice suggests the involvement of this protein in heart protection. Ex vivo experiments on cardiac explants could support this mechanism, as PKG blockade blunted protection against AngII-induced cardiac hypertrophy and fibrosis markers in H -ras -/- mice. Genetic modulation studies in cardiomyocytes and cardiac and embryonic fibroblasts revealed that the lack of H-Ras down-regulates the B-RAF/MEK/ERK pathway, which induces the glycogen synthase kinase-3β-dependent activation of the transcription factor, cAMP response element-binding protein, which is responsible for PKG-Iβ overexpression in H -ras -/- mouse embryonic fibroblasts. This study demonstrates that H- ras deletion protects against AngII-induced cardiac remodeling, possibly via a mechanism in which PKG-Iβ overexpression could play a partial role, and points to H-Ras and/or downstream proteins as potential therapeutic targets in cardiovascular disease.-Martín-Sánchez, P., Luengo, A., Griera, M., Orea, M. J., López-Olañeta, M., Chiloeches, A., Lara-Pezzi, E., de Frutos, S., Rodríguez-Puyol, M., Calleros, L., Rodríguez-Puyol, D. H- ras deletion protects against angiotensin II-induced arterial hypertension and cardiac remodeling through protein kinase G-Iβ pathway activation.
Synthesis, characterization and biological activity of some platinum(II) complexes with Schiff bases derived from salicylaldehyde, 2-furaldehyde and phenylenediamine.

PubMed

Gaballa, Akmal S; Asker, Mohsen S; Barakat, Atiat S; Teleb, Said M

2007-05-01

Four platinum(II) complexes of Schiff bases derived from salicylaldehyde and 2-furaldehyde with o- and p-phenylenediamine were reported and characterized based on their elemental analyses, IR and UV-vis spectroscopy and thermal analyses (TGA). The complexes were found to have the general formula [Pt(L)(H(2)O)(2)]Cl(2) x nH(2)O (where n=0 for complexes 1, 3, 4; n=1 for complex 2. The data obtained show that Schiff bases were interacted with Pt(II) ions in the neutral form as a bidentate ligand and the oxygens rather than the nitrogens are the most probable coordination sites. Square planar geometrical structure with two coordinated water molecules were proposed for all complexes The free ligands, and their metal complexes were screened for their antimicrobial activities against the following bacterial species: E. coli, B. subtilis, P. aereuguinosa, S. aureus; fungus A. niger, A. fluves; and the yeasts C. albican, S. cervisiea. The activity data show that the platinum(II) complexes are more potent antimicrobials than the parent Schiff base ligands against one or more microorganisms.
Murine lymphoma L5178Y cells resistant to purine antagonists: differences in cross-resistance to thioguanine-platinum(II) and selenoguanine-platinum(II).

PubMed

Kanzawa, F; Maeda, M; Sasaki, T; Hoshi, A; Kuretani, K

1982-02-01

To determine whether the antitumor activities of thioguanine-platinum(II) [TG-Pt(II)] and selenoguanine-platinum(II) [SeG-Pt(II)] are due to direct actions of these compounds or to the actions of their hydrolysis products, studies were made on a purine antagonist-resistant, murine lymphoma L5178Y/MP subline that lacked the anabolic enzyme hypoxanthine-guanine phosphoribosyltransferase necessary for tumor inhibition. The L5178Y/MP subline proved to be highly resistant to both TG-Pt(II) and thioguanine; the resistance ratios to the two compounds were almost identical. The subline showed high resistance to selenoguanine, but the cross-resistance to SeG-Pt(II) was negligible. Whether the compounds exhibit the delayed cytotoxicity characteristic of purine antagonists was also investigated. Delayed cytotoxicity was demonstrated for TG-Pt(II) as well as for thioguanine and other purine antagonists but not for SeG-Pt(II) or cis-dichlorodiammineplatinum(II). Experiments on cross-resistance and delayed cytotoxicity showed differences in the cytotoxicities of TG-Pt(II) and SeG-Pt(II): TG-Pt(II) exerted its activity through its hydrolysis product thioguanine, whereas SeG-Pt(II) compound was cytotoxic itself.
Synthesis, spectroscopic characterization, DFT optimization and biological activities of Schiff bases and their metal (II) complexes

NASA Astrophysics Data System (ADS)

Rauf, Abdur; Shah, Afzal; Munawar, Khurram Shahzad; Khan, Abdul Aziz; Abbasi, Rashda; Yameen, Muhammad Arfat; Khan, Asad Muhammad; Khan, Abdur Rahman; Qureshi, Irfan Zia; Kraatz, Heinz-Bernhard; Zia-ur-Rehman

2017-10-01

A Novel Schiff base, 3-(((4-chlorophenyl)imino)methyl)benzene-1,2-diol (HL1) was successfully synthesized along with a structurally similar Schiff base 3-(((4-bromophenyl)imino)methyl)benzene-1,2-diol (HL2). Both the Schiff bases were used to synthesize their zinc (II) and cobalt (II) complexes. These compounds were characterized by FTIR, 1H NMR, 13C NMR and elemental analysis. Metal complexes were confirmed by TGA. Crystals of Schiff bases were also characterized by X-ray analysis and experimental parameters were found in line with the theoretical parameters. Quantum mechanical approach was also used to fine useful structural parameters and to ensure the geometry of metal complexes. The photometric behaviors of all the synthesized compounds were investigated in a wide pH range using BR buffers. The appearance of isosbestic points indicated the existence of Schiff bases in more than one isomeric form. Moreover, these compounds were screened for enzyme inhibition; antibacterial, cytotoxic and in vivo antidiabetic activities and compounds were found active against one or other activity. Results indicate that ZnL22 is a good inhibitor of alkaline phosphatase enzyme and possess highest potential against diabetes, blood cholesterol level and cancer cells. This effort just provides preliminary data for some biological properties. Further investigations are required to precisely determine mechanistic pathways of their use towards drug development.
Preliminary X-ray crystallographic studies of BthTX-II, a myotoxic Asp49-phospholipase A{sub 2} with low catalytic activity from Bothrops jararacussu venom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Corrêa, L. C.; Marchi-Salvador, D. P.; Cintra, A. C. O.

2006-08-01

A myotoxic Asp49-PLA{sub 2} with low catalytic activity from B. jararacussu (BthTX-II) was crystallized in the monoclinic crystal system; a complete X-ray diffraction data set was collected and a molecular-replacement solution was obtained. The oligomeric structure of BthTX-II resembles those of the Asp49-PLA{sub 2} PrTX-III and all bothropic Lys49-PLA{sub 2}s. For the first time, a complete X-ray diffraction data set has been collected from a myotoxic Asp49-phospholipase A{sub 2} (Asp49-PLA{sub 2}) with low catalytic activity (BthTX-II from Bothrops jararacussu venom) and a molecular-replacement solution has been obtained with a dimer in the asymmetric unit. The quaternary structure of BthTX-II resemblesmore » the myotoxin Asp49-PLA{sub 2} PrTX-III (piratoxin III from B. pirajai venom) and all non-catalytic and myotoxic dimeric Lys49-PLA{sub 2}s. In contrast, the oligomeric structure of BthTX-II is different from the highly catalytic and non-myotoxic BthA-I (acidic PLA{sub 2} from B. jararacussu). Thus, comparison between these structures should add insight into the catalytic and myotoxic activities of bothropic PLA{sub 2}s.« less

Design, synthesis and characterization of macrocyclic ligand based transition metal complexes of Ni(II), Cu(II) and Co(II) with their antimicrobial and antioxidant evaluation

NASA Astrophysics Data System (ADS)

Gull, Parveez; Malik, Manzoor Ahmad; Dar, Ovas Ahmad; Hashmi, Athar Adil

2017-04-01

Three new complexes Ni(II), Cu(II) and Co(II) were synthesized of macrocyclic ligand derived from 1, 4-dicarbonyl-phenyl-dihydrazide and O-phthalaldehyde in the ratio of 2:2. The synthesized compounds were characterized by elemental analyses, molar conductance, magnetic susceptibility measurements, FTIR, UV-Vis., Mass and 1H NMR spectral studies. The electronic spectra of the metal complexes indicate a six coordinate octahedral geometry of the central metal ion. These metal complexes and the ligand were evaluated for antimicrobial activity against bacteria (E. coli, B. subtilis, S. aureus) and fungi (A. niger, A. flavus, C. albicans) and compared against standard drugs chloramphenicol and nystatin respectively. In addition, the antioxidant activity of the compounds was also investigated through scavenging effect on DPPH radicals.
Photoactive platinum(II) complexes of nonsteroidal anti-inflammatory drug naproxen: Interaction with biological targets, antioxidant activity and cytotoxicity.

PubMed

Srivastava, Payal; Singh, Khushbu; Verma, Madhu; Sivakumar, Sri; Patra, Ashis K

2018-01-20

The effect on the therapeutic efficacy of Pt(II) complexes on combining non-steroidal anti-inflammatory drugs (NSAIDs) is an attractive strategy to circumvent chronic inflammation mediated by cancer and metastasis. Two square-planar platinum(II) complexes: [Pt(dach)(nap)Cl] (1) and [Pt(dach)(nap) 2 ] (2), where dach = (1R,2R)-dichloro(cyclohexane-1,2-diamine) and NSAID drug naproxen (nap), have been designed for studying their biological activity. The naproxen bound to the Pt(II) centre get released upon photoirradiation with low-power UV-A light as confirmed by the significant enhancement in emission intensities of the complexes. The compounds were evaluated for their photophysical properties, photostability, reactivity with 5'-guanosine monophophosphate (5'-GMP), interactions with CT-DNA and BSA, antioxidant activity and reactive oxygen species mediated photo-induced DNA damage properties. ESI-MS studies demonstrated the formation of bis-adduct with 5'-GMP and the formation of Pt II -DNA crosslinks by gel electrophoretic mobility shift assay and ITC studies. The interaction of the complexes 1 and 2 with the CT-DNA exhibits potential binding affinity (K b ∼ 10 4 M -1 , K app ∼ 10 5 M -1 ), implying intercalation to CT-DNA through planar naphthyl ring of the complexes. Both the complexes also exhibit strong binding affinity towards BSA (K BSA ∼ 10 5 M -1 ). The complexes exhibit efficient DNA damage activity on irradiation at 365 nm via formation of singlet oxygen ( 1 O 2 ) and hydroxyl radical ( • OH) under physiological conditions. Both the complexes were cytotoxic in dark and exhibit significant enhancement of cytotoxicity upon photo-exposure against HeLa and HepG2 cancer cells giving IC 50 values ranging from 8 to 12 μM for 1 and 2. The cellular internalization data showed cytosolic and nuclear localization of the complexes in the HeLa cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Lipidated promiscuous peptide augments the expression of MHC-II molecules on dendritic cells and activates T cells

PubMed Central

Gowthaman, Uthaman; Rai, Pradeep K.; Zeng, Weiguang; Jackson, David C.; Agrewala, Javed N.

2013-01-01

Background & objectives: In spite of the fact that BCG is the most widely used vaccine, tuberculosis (TB) continues to be a major killer disease in TB-endemic regions. Recently, many emerging evidences from the published literature indicate the role of environmental mycobacteria in blocking the processing and presentation of BCG antigens and thereby impairing with suboptimal generation of protective T cells. To surmount this problem associated with BCG, we constructed a novel lipopeptide (L91) by conjugating a promiscuous peptide consisting of CD4+ T-helper epitope of sequence of 91-110 of 16 kDa antigen of Mycobacterium tuberculosis to Pam2Cys, an agonist of Toll-like receptor-2. Methods: Mice were immunized subcutaneously with 20 nmol of L91, followed by a booster with 10 nmol, after an interval of 21 days of primary immunization. Animals were sacrificed after seven days of post-booster immunization. L91 induced immune response was characterized by the expression of MHC-II and CD74 on the surface of dendritic cells (DCs) by flowcytometry. Cytokines (IL-4, IL-10, IFN-γ) secretion and anti-peptide antibodies were measured by ELISA. Results: Self-adjuvanting lipopeptide vaccine (L91) was directly bound to MHC-II molecules and without requiring extensive processing for its presentation to T cells. It stimulated and activated dendritic cells and augmented the expression of MHC-II molecules. Further, it activated effector CD4 T cells to mainly secrete interferon (IFN)-γ but not interleukin (IL)-4 and IL-10. L91 did not elicit anti-peptide antibodies. Interpretation & conclusions: The findings suggest that L91 evokes maturation and upregulation of MHC class II molecules and promotes better antigen presentation and, therefore, optimum activation of T cells. L91 mainly induces effector Th1 cells, as evidenced by predominant release of IFN-γ, consequently can mount favourable immune response against M. tuberculosis. As L91 does not provoke the generation of anti
Polymeric Cd(II), trinuclear and mononuclear Ni(II) complexes of 5-methyl-4-phenyl-1,2,4-triazole-3-thione: Synthesis, structural characterization, thermal behaviour, fluorescence properties and antibacterial activity

NASA Astrophysics Data System (ADS)

Bharty, M. K.; Paswan, S.; Dani, R. K.; Singh, N. K.; Sharma, V. K.; Kharwar, R. N.; Butcher, R. J.

2017-02-01

Syntheses of a polymeric Cd(II) complex, [Cd(mptt)2]n (1), a trinuclear Ni(II) complex, [Ni3(μ-mptt)4(μ-H2O)2(H2O)2(ttfa)2]·3H2O (2) and a mononuclear Ni(II) complex [Ni(mptt)2(en)2] (3) have been performed using the ligand 5-methyl-4-phenyl-1,2,4-triazole-3-thione (Hmptt) and nickel(II)/cadmium(II) salts {ttfa = thenoyltrifluroacetonate). The ligand and the complexes have been characterized by various physicochemical methods in addition to their single crystal X-ray structure. The Cd centre in complex 1 adopts a distorted tetrahedral geometry with one sulfur atom and two mptt ligands provide three nitrogen atoms from three triazole units. The sulfur atom of the ligand binds covalently and overall the ligand acts as uninigative N,S/N,N bidentate moiety. The polymeric structure of complex 1 results from the N atoms of the neighboring triazole units coordinating with the Cd(II) centre. The three Ni(II) centres in the trinuclear Ni(II) complex 2 form a linear arrangement and all have six coordinated arrangements. The middle Ni(II) binds with four deprotonated triazole ring nitrogens and two water molecules form two bridges. The terminal Ni(II) centres bind through two thenoyl oxygens, two triazole nitrogens and water molecules that formed bridges with the middle Ni centre. In complex 3, the nickel(II) centre is covalently bonded through two deprotonated triazole ring nitrogens from two ligand moieties and other four sites are occupied by four nitrogens from two bidentate en ligands. Thermogravimetric analyses (TGA) of the complexes indicated for NiO as the final residue. The bioefficacy of the ligand and complexes 2 and 3 have been examined against the growth of bacteria to evaluate their anti-microbial potential. Complex 2 showed high antibacterial activity as compared to the ligand and complex 3. Complexes 1, 2 and 3 are fluorescent materials with maximum emissions at 425, 421 and 396 nm at an excitation wavelength of 323, 348 and 322 nm, respectively.
Platelet activation in essential hypertension during exercise: pre- and post-treatment changes with an angiotensin II receptor blocker.

PubMed

Gkaliagkousi, Eugenia; Gavriilaki, Eleni; Yiannaki, Efi; Markala, Dimitra; Papadopoulos, Nikolaos; Triantafyllou, Areti; Anyfanti, Panagiota; Petidis, Konstantinos; Garypidou, Vasileia; Doumas, Michael; Ferro, Albert; Douma, Stella

2014-04-01

Acute exercise may exert deleterious effects on the cardiovascular system through a variety of pathophysiological mechanisms, including increased platelet activation. However, the degree of exercise-induced platelet activation in untreated hypertensive (UH) individuals as compared with normotensive (NT) individuals has yet to be established. Furthermore, the effect of antihypertensive treatment on exercise-induced platelet activation in essential hypertension (EH) remains unknown. Study 1 consisted of 30 UH and 15 NT subjects. UH subjects who received treatment were included in study 2 and were followed-up after a 3-month treatment period with an angiotensin II receptor blocker (ARB; valsartan). Circulating monocyte-platelet aggregates (MPA) and platelet P-selectin were measured as platelet activation markers at baseline, immediately after a treadmill exercise test, and 10, 30, and 90 minutes later. Maximal platelet activation was observed at 10 minutes after peak exercise in both groups. In UH subjects, MPA levels remained increased at 30 minutes after peak exercise, despite BP fall to baseline levels. MPA levels were significantly higher in UH subjects than NT subjects at maximal exercise and at 10 and 30 minutes of recovery. Post-treatment MPA levels increased significantly only at 10 minutes into recovery and were similar to those of NT subjects. Acute high-intensity exercise exaggerates platelet activation in untreated patients with EH compared with NT individuals. Angiotensin II receptor blockade with adequate BP control greatly improves exercise-induced platelet activation in EH. Further studies are needed to clarify whether this phenomenon depends purely on BP lowering or benefits also from the pleiotropic effects of ARBs.
Physicochemical impact studies of gamma rays on "aspirin" analgesics drug and its metal complexes in solid form: Synthesis, spectroscopic and biological assessment of Ca(II), Mg(II), Sr(II) and Ba(II) aspirinate complexes

NASA Astrophysics Data System (ADS)

Refat, Moamen S.; Sharshar, T.; Elsabawy, Khaled M.; Heiba, Zein K.

2013-09-01

Metal aspirinate complexes, M2(Asp)4, where M is Mg(II), Ca(II), Sr(II) or Ba(II) are formed by refluxed of aspirin (Asp) with divalent non-transition metal ions of group (II) and characterized by elemental analysis and spectroscopic measurements (infrared, electronic, 1H NMR, Raman, X-ray powder diffraction and scanning electron microscopy). Elemental analysis of the chelates suggests the stoichiometry is 1:2 (metal:ligand). Infrared spectra of the complexes agree with the coordination to the central metal atom through three donation sites of two oxygen atoms of bridge bidentate carboxylate group and oxygen atom of sbnd Cdbnd O of acetyl group. Infrared spectra coupled with the results of elemental analyzes suggested a distorted octahedral structure for the M(II) aspirinate complexes. Gamma irradiation was tested as a method for stabilization of aspirin as well as their complexes. The effect of gamma irradiation, with dose of 80 Gy, on the properties of aspirinate complexes was studied. The aspirinate chelates have been screened for their in vitro antibacterial activity against four bacteria, gram-positive (Bacillus subtilis and Staphylococcus aureus) and gram-negative (Escherichia coli and Pseudomonas aeruginosa) and two strains of fungus (Aspergillus flavus and Candida albicans). The metal chelates were shown to possess more antibacterial activity than the free aspirin chelate.
A new cadmium(II) complex with bridging dithiolate ligand: Synthesis, crystal structure and antifungal activity study

NASA Astrophysics Data System (ADS)

Singh, Mahesh Kumar; Sutradhar, Sanjit; Paul, Bijaya; Adhikari, Suman; Laskar, Folguni; Butcher, Raymond J.; Acharya, Sandeep; Das, Arijit

2017-07-01

A new polymeric complex of Cd(II) with 1,1-dicyanoethylene- 2,2-dithiolate [ i-MNT2- = {S2C:C(CN)2}2- ] as a bridging ligand has been synthesized and characterized on the basis of spectroscopy and single-crystal X-ray diffraction analysis. Single crystal X-ray diffraction analysis reveals that the Cadmium (II) complex is six coordinated 1D polymeric in nature. Biological screening effects in vitro of the synthesized polymeric complex has been tested against five fungi Synchitrium endobioticum, Pyricularia oryzae, Helminthosporium oryzae, Candida albicans(ATCC10231), Trichophyton mentagrophytes by the disc diffusion method. In vitro antifungal screening indicates that the complex exhibits fungistatic and fungicidal antifungal activity whereas K2i-MNT.H2O became silent on Synchitrium endobioticum, Pyricularia oryzae, Helminthosporium oryzae, Candida albicans (ATCC10231), Trichophyton mentagrophytes.
Preparation of Enteromorpha prolifera-based cetyl trimethyl ammonium bromide-doped activated carbon and its application for nickel(II) removal.

PubMed

Wang, Man; Hao, Fang; Li, Gang; Huang, Ji; Bao, Nan; Huang, Lihui

2014-06-01

Activated carbon was prepared from Enteromorpha prolifera (EP) by H3PO4 activation in the presence of doped cetyl trimethyl ammonium bromide (CTAB), producing EPAC-CTAB. The thermal decomposition process of the activated carbon substrate was identified by thermo-gravimetric analysis. Scanning electron microscope (SEM), N2 adsorption/desorption, Fourier transform infrared spectroscopy (FTIR), Boehm titration, and X-ray Photoelectron Spectroscopy (XPS) were employed to characterize the physicochemical properties of native EPAC and EPAC-CTAB. EPAC-CTAB exhibited smaller surface area (689.0m(2)/g) and lower total pore volume (0.361cm(3)/g) than those of EPAC (1045.8m(2)/g and 1.048cm(3)/g), while the number of acidic groups, oxygen and nitrogen groups on the surface of EPAC-CTAB increased through CTAB doping. The batch kinetics and isotherm adsorption studies of nickel(II) onto the adsorbents were examined and agreed well with the pseudo-second-order model and the Langmuir model. The maximum adsorption capacity determined from the Langmuir model was 16.9mg/g for EPAC and 49.8mg/g for EPAC-CTAB. Under acidic condition, the adsorption of nickel(II) onto EPAC and EPAC-CTAB was hindered due to ion competition and electrostatic repulsion. The results indicated that using CTAB as a dopant for EPAC modification could markedly enhance the nickel(II) removal. Copyright © 2014. Published by Elsevier Inc.
Diastereoselective Radical‐Type Cyclopropanation of Electron‐Deficient Alkenes Mediated by the Highly Active Cobalt(II) Tetramethyltetraaza[14]annulene Catalyst

PubMed Central

Chirila, Andrei; Gopal Das, Braja; Paul, Nanda D.

2017-01-01

Abstract A new protocol for the catalytic synthesis of cyclopropanes using electron‐deficient alkenes is presented, which is catalysed by a series of affordable, easy to synthesise and highly active substituted cobalt(II) tetraaza[14]annulenes. These catalysts are compatible with the use of sodium tosylhydrazone salts as precursors to diazo compounds in one‐pot catalytic transformations to afford the desired cyclopropanes in almost quantitative yields. The reaction takes advantage of the metalloradical character of the Co complexes to activate the diazo compounds. The reaction is practical and fast, and proceeds from readily available starting materials. It does not require the slow addition of diazo reagents or tosylhydrazone salts or heating and tolerates many solvents, which include protic ones such as MeOH. The CoII complexes derived from the tetramethyltetraaza[14]annulene ligand are easier to prepare than cobalt(II) porphyrins and present a similar catalytic carbene radical reactivity but are more active. The reaction proceeds at 20 °C in a matter of minutes and even at −78 °C in a few hours. The catalytic system is robust and can operate with either the alkene or the diazo reagent as the limiting reagent, which inhibits the dimerisation of diazo compounds totally. The protocol has been applied to synthesise a variety of substituted cyclopropanes. High yields and selectivities were achieved for various substrates with an intrinsic preference for trans cyclopropanes. PMID:28529668
Rapid and efficient removal of Pb(II) from aqueous solutions using biomass-derived activated carbon with humic acid in-situ modification.

PubMed

Guo, Zizhang; Zhang, Jian; Kang, Yan; Liu, Hai

2017-11-01

This study developed an humic acid (HA) in-situ modified activated carbon adsorbent (AC-HA) for the rapid and efficient removal of Pb(II) from aqueous media, and adsorption mechanisms are discussed. The physicochemical characteristics of activated carbons (AC) were investigated via N 2 adsorption/desorption, scanning electron microscopy (SEM), Boehm's titration method and Fourier transform infrared spectroscopy (FTIR). AC-HA exhibited richer oxygen-containing functional groups than the original AC. In addition, the removal performance of AC-HA (250.0mg/g) toward Pb(II) was greatly improved compared with the original AC (166.7mg/g). The batch adsorption study results revealed that the Pb(II) adsorption data were best fit by the pseudo-second-order model of kinetics and Langmuir isotherm of isothermals, and therefore, the effect of the solution pH was studied. The superior performance of AC-HA was attributed to the HA modification, which contains numbers of groups and has a strong π-π interaction binding energy with AC and Pb(II) species. The adsorption mechanisms were confirmed via the XPS study. More importantly, the modified method is simple and has a low cost of production. Copyright © 2017 Elsevier Inc. All rights reserved.
Combination of sawdust from teak wood and rice husk activated carbon as adsorbent of Pb(II) ion and its analysis using solid-phase spectrophotometry (sps)

NASA Astrophysics Data System (ADS)

Saputro, S.; Mahardiani, L.; Wulandari, D. A.

2018-03-01

This research aimed to know the usage of sawdust of teak wood and rice husk waste as Pb (II) ion adsorbents in simulated liquid waste, the combined optimum mass required adsorbent to adsorb Pb(II) ion, the sensitivity of the solid-phase spectrophotometry (sps) method in determining the decrease of Pb (II) metal ion levels in the μg/L level. This research was conducted by experimental method in laboratory. Adsorbents used in this study were charcoal of sawdust sawdust activated using 15% ZnCl2 solution and activated rice husk using 2 N NaOH solution. The adsorption processes of sawdust and rice husk with Pb(II) solution was done by variation of mass combination with a ratio of 1: 0; 0: 1; 1: 1; 1: 2; and 2: 1. Analysis of Pb(II) ion concentration using SPS and characterization of sawdust and rice husk adsorbent ads using FTIR. The results showed that activated charcoal from sawdust of teak wood and rice husks can be used as Pb (II) metal ion adsorbents with adsorption capacity of 0.86 μg/L, charcoal from sawdust of teak wood and rice husk adsorbent with a combination of optimum mass contact of sawdust and rice husk is 2:1 as much as 3 grams can adsorb 42.80 μg/L. Solid-phase spectophotometry is a sensitive method for analysis of concentration decreasing levels of Pb(II) ion, after it was absorbed by sawdust of teak wood and rice husk with high sensitivity and has the limit of detection (LOD) of 0.06 μg/L.
The Role of miR-330-3p/PKC-α Signaling Pathway in Low-Dose Endothelial-Monocyte Activating Polypeptide-II Increasing the Permeability of Blood-Tumor Barrier

PubMed Central

Liu, Jiahui; Liu, Libo; Chao, Shuo; Liu, Yunhui; Liu, Xiaobai; Zheng, Jian; Chen, Jiajia; Gong, Wei; Teng, Hao; Li, Zhen; Wang, Ping; Xue, Yixue

2017-01-01

This study was performed to determine whether EMAP II increases the permeability of the blood-tumor barrier (BTB) by affecting the expression of miR-330-3p as well as its possible mechanisms. We determined the over-expression of miR-330-3p in glioma microvascular endothelial cells (GECs) by Real-time PCR. Endothelial monocyte-activating polypeptide-II (EMAP-II) significantly decreased the expression of miR-330-3p in GECs. Pre-miR-330-3p markedly decreased the permeability of BTB and increased the expression of tight junction (TJ) related proteins ZO-1, occludin and claudin-5, however, anti-miR-330-3p had the opposite effects. Anti-miR-330-3p could enhance the effect of EMAP-II on increasing the permeability of BTB, however, pre-miR-330-3p partly reversed the effect of EMAP-II on that. Similarly, anti-miR-330-3p improved the effects of EMAP-II on increasing the expression levels of PKC-α and p-PKC-α in GECs and pre-miR-330-3p partly reversed the effects. MiR-330-3p could target bind to the 3′UTR of PKC-α. The results of in vivo experiments were similar to those of in vitro experiments. These suggested that EMAP-II could increase the permeability of BTB through inhibiting miR-330-3p which target negative regulation of PKC-α. Pre-miR-330-3p and PKC-α inhibitor decreased the BTB permeability and up-regulated the expression levels of ZO-1, occludin and claudin-5 while anti-miR-330-3p and PKC-α activator brought the reverse effects. Compared with EMAP-II, anti-miR-330-3p and PKC-α activator alone, the combination of the three combinations significantly increased the BTB permeability. EMAP-II combined with anti-miR-330-3p and PKCα activator could enhance the DOX’s effects on inhibiting the cell viabilities and increasing the apoptosis of U87 glioma cells. Our studies suggest that low-dose EMAP-II up-regulates the expression of PKC-α and increases the activity of PKC-α by inhibiting the expression of miR-330-3p, reduces the expression of ZO-1, occludin and
Batch and dynamic sorption of Ni(II) ions by activated carbon based on a native lignocellulosic precursor.

PubMed

Nabarlatz, Debora; de Celis, Jorge; Bonelli, Pablo; Cukierman, Ana Lea

2012-04-30

Vinal-derived Activated Carbon (VAC) developed by phosphoric acid activation of sawdust from Prosopis ruscifolia native wood was tested for the adsorption of Ni(II) ions from dilute solutions in both batch and dynamic modes, comparing it with a Commercial Activated Carbon (CAC). Batch experiments were performed to determine adsorption kinetics and equilibrium isotherms for both carbons. It was possible to remove near 6.55 mg Ni g(-1) VAC and 7.65 mg Ni g(-1) CAC after 5 h and 10 h contact time, respectively. A pseudo second order equation fitted well with the kinetics of the process, and Langmuir adsorption model was used to adjust the experimental results concerning the adsorption isotherm. The parameters obtained indicate a stronger interaction between sorbent and sorbate for VAC (K = 26.56 L mmol(-1)) than for CAC (K = 19.54 L mmol(-1)). Continuous experiments were performed in a fixed-bed column packed with the investigated carbons, evaluating the influence of operational parameters such as flow rate, bed height and feed concentration on the breakthrough curves obtained. The breakthrough occurred more slowly for low concentrations of the metal ion in the feed, low flow rates and high bed height. The breakthrough curves were properly represented by Hall's model for both carbon types. Regeneration of the vinal activated carbon in column was tested, obtaining the same breakthrough curve in a new cycle of use. Finally, vinal-derived activated carbon can effectively be used to treat wastewater having until 30 ppm Ni(II). Copyright © 2011 Elsevier Ltd. All rights reserved.
Valsartan ameliorates ageing-induced aorta degeneration via angiotensin II type 1 receptor-mediated ERK activity

PubMed Central

Shan, HaiYan; Zhang, Siyang; Li, Xuelian; yu, Kai; Zhao, Xin; Chen, Xinyue; Jin, Bo; Bai, XiaoJuan

2014-01-01

Angiotensin II (Ang II) plays important roles in ageing-related disorders through its type 1 receptor (AT1R). However, the role and underlying mechanisms of AT1R in ageing-related vascular degeneration are not well understood. In this study, 40 ageing rats were randomly divided into two groups: ageing group which received no treatment (ageing control), and valsartan group which took valsartan (selective AT1R blocker) daily for 6 months. 20 young rats were used as adult control. The aorta structure were analysed by histological staining and electron microscopy. Bcl-2/Bax expression in aorta was analysed by immunohistochemical staining, RT-PCR and Western blotting. The expressions of AT1R, AT2R and mitogen-activated protein kinases (MAPKs) were detected. Significant structural degeneration of aorta in the ageing rats was observed, and the degeneration was remarkably ameliorated by long-term administration of valsartan. With ageing, the expression of AT1R was elevated, the ratio of Bcl-2/Bax was decreased and meanwhile, an important subgroup of MAPKs, extracellular signal-regulated kinase (ERK) activity was elevated. However, these changes in ageing rats could be reversed to some extent by valsartan. In vitro experiments observed consistent results as in vivo study. Furthermore, ERK inhibitor could also acquire partial effects as valsartan without affecting AT1R expression. The results indicated that AT1R involved in the ageing-related degeneration of aorta and AT1R-mediated ERK activity was an important mechanism underlying the process. PMID:24548645
Copper(II) complexes with 4-(1H-1, 2, 4-trizol-1-ylmethyl) benzoic acid: Syntheses, crystal structures and antifungal activities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiong, Pingping; Li, Jie; Bu, Huaiyu, E-mail: 7213792@qq.com

2014-07-01

Reaction of Cu(II) with an asymmetric semi-rigid organic ligand 4-(1H-1, 2, 4-trizol-1-ylmethyl) benzoic acid (HL), yielded five compounds, [Cu{sub 0.5}L]{sub n} (1), [Cu(HL){sub 2}Cl{sub 2}]{sub n} (2), [Cu(HL){sub 2}Cl{sub 2}(H{sub 2}O)] (3), [Cu(L){sub 2}(H{sub 2}O)]{sub n} (4) and [Cu(L)(phen)(HCO{sub 2})]{sub n} (5), which have been fully characterized by infrared spectroscopy, elemental analysis, and single-crystal X-ray diffraction. As for compounds 1, 2 and 5, Cu(II) is bridged through HL, Cl{sup -}, and formic acid, respectively, featuring 1D chain-structure. In compound 3, Cu(II) with hexahedral coordination sphere is assembled through hydrogen-bonding into 3D supramolecular framework. In compound 4, 1D chain units –Cu–O–Cu–O–more » are ligand-bridged into a 3D network. All compounds were tested on fungi (Fusarium graminearum, Altemaria solani, Macrophoma kawatsukai, Alternaria alternata and Colletotrichum gloeosporioides). Compound 1 exhibits a better antifungal effect compared to other compounds. An effect of structure on the antifungal activity has also been correlated. - Graphical abstract: Copper(II) compounds with 4-(1H-1, 2, 4-trizol-1-ylmethyl) benzoic acid, were prepared, structurally characterized and investigated for antifungal activity. - Highlights: • The title compounds formed by thermodynamics and thermokinetics. • The five compounds show higher inhibition percentage than reactants. • The structure effect on the antifungal activity.« less
Chromospheres of late-type active and quiescent dwarfs. III - Variability of CA II H emission profiles

NASA Astrophysics Data System (ADS)

Garcia Lopez, R. J.; Crivellari, L.; Beckman, J. E.; Rebolo, R.

1992-08-01

We have used high-resolution spectra of the Ca II H resonance line in late-type dwarfs, obtained with high S:N ratios, over a period of four years to widen our understanding of the dynamical behavior of the Ca II emission cores. All of the stars dealt with in this article, which are chromospherically active, show variability both in core emission flux and line width. They also show significant wavelength shifts with time of order hundreds of meters per second in the mean core wavelength, and with lower amplitude in the H3 self-absorption, compared to the photospheric rest wavelength of Ca II H. Comparing the emission core shifts with those observed in the H3 features, we find, for the first time, direct prima facie evidence for vertical chromospheric velocity fields, which show stability in sense over periods of years in a given star, with notable modulation in gradient, and which differ in gradient from star to star. We present evidence to show that the observed effects are almost certainly not due to projected rotational modulation, and offer new prospects, given spectral measurements closely sampled in time, for investigating the vertical velocity structures of chromospheres.
On-line solid phase selective separation and preconcentration of Cd(II) by solid-phase extraction using carbon active modified with methyl thymol blue.

PubMed

Ensafi, Ali A; Ghaderi, Ali R

2007-09-05

An on-line flow system was used to develop a selective and efficient on-line sorbent extraction preconcentration system for cadmium. The method is based on adsorption of cadmium ions onto the activated carbon modified with methyl thymol blue. Then the adsorbed ions were washed using 0.5M HNO(3) and the eluent was used to determine the Cd(II) ions using flame atomic absorption spectrometry. The results obtained show that the modified activated carbon has the greatest adsorption capacity of 80 microg of Cd(II) per 1.0 g of the solid phase. The optimal pH value for the quantitative preconcentration was 9.0 and full desorption is achieved by using 0.5M HNO(3) solution. It is established that the solid phase can be used repeatedly without a considerable adsorption capacity loss. The detection limit was less than 1 ngmL(-1) Cd(II), with an enrichment factor of 1000. The calibration graph was linear in the range of 1-2000 ngmL(-1) Cd(II). The developed method has been applied to the determination of trace cadmium (II) in water samples and in the following reference materials: sewage sludge (CRM144R), and sea water (CASS.4) with satisfactory results. The accuracy was assessed through recovery experiments.
Phytochemicals as Anticancer and Chemopreventive Topoisomerase II Poisons

PubMed Central

Ketron, Adam C.

2013-01-01

Phytochemicals are a rich source of anticancer drugs and chemopreventive agents. Several of these chemicals appear to exert at least some of their effects through interactions with topoisomerase II, an essential enzyme that regulates DNA supercoiling and removes knots and tangles from the genome. Topoisomerase II-active phytochemicals function by stabilizing covalent protein-cleaved DNA complexes that are intermediates in the catalytic cycle of the enzyme. As a result, these compounds convert topoisomerase II to a cellular toxin that fragments the genome. Because of their mode of action, they are referred to as topoisomerase II poisons as opposed to catalytic inhibitors. The first sections of this article discuss DNA topology, the catalytic cycle of topoisomerase II, and the two mechanisms (interfacial vs. covalent) by which different classes of topoisomerase II poisons alter enzyme activity. Subsequent sections discuss the effects of several phytochemicals on the type II enzyme, including demethyl-epipodophyllotoxins (semisynthetic anticancer drugs) as well as flavones, flavonols, isoflavones, catechins, isothiocyanates, and curcumin (dietary chemopreventive agents). Finally, the leukemogenic potential of topoisomerase II-targeted phytochemicals is described. PMID:24678287
UCS protein Rng3p activates actin filament gliding by fission yeast myosin-II

PubMed Central

Lord, Matthew; Pollard, Thomas D.

2004-01-01

We purified native Myo2p/Cdc4p/Rlc1p (Myo2), the myosin-II motor required for cytokinesis by Schizosaccharomyces pombe. The Myo2p heavy chain associates with two light chains, Cdc4p and Rlc1p. Although crude Myo2 supported gliding motility of actin filaments in vitro, purified Myo2 lacked this activity in spite of retaining full Ca-ATPase activity and partial actin-activated Mg-ATPase activity. Unc45-/Cro1p-/She4p-related (UCS) protein Rng3p restored the full motility and actin-activated Mg-ATPase activity of purified Myo2. The COOH-terminal UCS domain of Rng3p alone restored motility to pure Myo2. Thus, Rng3p contributes directly to the motility activity of native Myo2. Consistent with a role in Myo2 activation, Rng3p colocalizes with Myo2p in the cytokinetic contractile ring. The absence of Rlc1p or mutations in the Myo2p head or Rng3p compromise the in vitro motility of Myo2 and explain the defects in cytokinesis associated with some of these mutations. In contrast, Myo2 with certain temperature-sensitive forms of Cdc4p has normal motility, so these mutations compromise other functions of Cdc4p required for cytokinesis. PMID:15504913
Conserved water mediated recognition and the dynamics of active site Cys 331 and Tyr 411 in hydrated structure of human IMPDH-II.

PubMed

Bairagya, Hridoy R; Mukhopadhyay, Bishnu P; Bera, Asim K

2011-01-01

Inosine monophosphate dehydrogenase (IMPDH) of human is involved in GMP biosynthesis pathway, increased level of IMPDH-II (an isoform of enzyme) activity have found in leukemic and sarcoma cells. Modeling and extensive molecular dynamics simulation (15 ns) studies of IMPDH-II (1B3O PDB structure) have indicated the intricate involvement of four conserved water molecules (W 1, W 2, W 3, and W 4) in the conformational transition or the mobilities of "flap" (residues 400-450) and "loop" (residues 325-342) regions in enzyme. The stabilization of active site residues Asn 303, Gly 324, Ser 329, Cys 331, Asp 364, and Tyr 411 through variable H-bonding coordination from the conserved water molecular center seems interesting in the uninhibited hydrated form of human IMPDH-II structures. This conformational transition or the flexibility of mobile regions, water molecular recognition to active site residues Cys 331 and Tyr 411, and the presence of a hydrophilic cavity approximately 540 Å(3) (enclaved by the loop and flap region) near the C-terminal surface of this enzyme may explore a rational hope toward the water mimic inhibitor or anticancer agent design for human. 2010 John Wiley & Sons, Ltd.

Metal based biologically active compounds: Design, synthesis, DNA binding and antidiabetic activity of 6-methyl-3-formyl chromone derived hydrazones and their metal (II) complexes.

PubMed

Philip, Jessica Elizabeth; Shahid, Muhammad; Prathapachandra Kurup, M R; Velayudhan, Mohanan Puzhavoorparambil

2017-10-01

Two chromone hydrazone ligands HL 1 and HL 2 were synthesized and characterized by elemental analyses, IR, 1 H NMR & 13 C NMR, electronic absorption and mass spectra. The reactions of the chromone hydrazones with transition metals such as Ni, Cu, and Zn (II) salts of acetate afforded mononuclear metal complexes. Characterization and structure elucidation of the prepared chromone hydrazone metal (II) complexes were done by elemental, IR, electronic, EPR spectra and thermo gravimetric analyses as well as conductivity and magnetic susceptibility measurements. The spectroscopic data showed that the ligand acts as a mono basic bidentate with coordination sites are azomethine nitrogen and hydrazonic oxygen, and they exhibited distorted geometry. The biological studies involved antidiabetic activity i.e. enzyme inhibition of α-amylase and α-glucosidase, Calf Thymus - DNA (CT-DNA) interaction and molecular docking. Potential capacity of synthesized compounds to inhibit the α-amylase and α-glucosidase activity was assayed whereas DNA interaction studies were carried out with the help UV-Vis absorption titration and viscosity method. The docking studies of chromone hydrazones show that they are minor groove binders. Complexes were found to be good DNA - intercalates. Chromone hydrazones and its transition metal complexes have shown comparable antidiabetic activity with a standard drug acarbose. Copyright © 2017 Elsevier B.V. All rights reserved.
Generation of an activation map for decommissioning planning of the Berlin Experimental Reactor-II

NASA Astrophysics Data System (ADS)

Lapins, Janis; Guilliard, Nicole; Bernnat, Wolfgang

2017-09-01

The BER-II is an experimental facility with 10 MW that was operated since 1974. Its planned operation will end in 2019. To support the decommissioning planning, a map with the overall distribution of relevant radionuclides has to be created according to the state of the art. In this paper, a procedure to create these 3-d maps using a combination of MCNP and deterministic methods is presented. With this approach, an activation analysis is performed for the whole reactor geometry including the most remote parts of the concrete shielding.
Synthesis, DNA Cleavage Activity, Cytotoxicity, Acetylcholinesterase Inhibition, and Acute Murine Toxicity of Redox-Active Ruthenium(II) Polypyridyl Complexes.

PubMed

Alatrash, Nagham; Narh, Eugenia S; Yadav, Abhishek; Kim, Mahn-Jong; Janaratne, Thamara; Gabriel, James; MacDonnell, Frederick M

2017-07-06

Four mononuclear [(L-L) 2 Ru(tatpp)] 2+ and two dinuclear [(L-L) 2 Ru(tatpp)Ru(L-L) 2 ] 4+ ruthenium(II) polypyridyl complexes (RPCs) containing the 9,11,20,22-tetraazatetrapyrido[3,2-a:2',3'-c:3'',2''-l:2''',3'''-n]pentacene (tatpp) ligand were synthesized, in which L-L is a chelating diamine ligand such as 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 3,4,7,8-tetramethyl-1,10-phenanthroline (Me 4 phen) or 4,7-diphenyl-1,10-phenanthroline (Ph 2 phen). These Ru-tatpp analogues all undergo reduction reactions with modest reducing agents, such as glutathione (GSH), at pH 7. These, plus several structurally related but non-redox-active RPCs, were screened for DNA cleavage activity, cytotoxicity, acetylcholinesterase (AChE) inhibition, and acute mouse toxicity, and their activities were examined with respect to redox activity and lipophilicity. All of the redox-active RPCs show single-strand DNA cleavage in the presence of GSH, whereas none of the non-redox-active RPCs do. Low-micromolar cytotoxicity (IC 50 ) against malignant H358, CCL228, and MCF7 cultured cell lines was mainly restricted to the redox-active RPCs; however, they were substantially less toxic toward nonmalignant MCF10 cells. The IC 50 values for AChE inhibition in cell-free assays and the acute toxicity of RPCs in mice revealed that whereas most RPCs show potent inhibitory action against AChE (IC 50 values <15 μm), Ru-tatpp complexes as a class are surprisingly well tolerated in animals relative to other RPCs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Adsorption of Pb(II), Cu(II), Cd(II), Zn(II), Ni(II), Fe(II), and As(V) on bacterially produced metal sulfides.

PubMed

Jong, Tony; Parry, David L

2004-07-01

The adsorption of Pb(II), Cu(II), Cd(II), Zn(II), Ni(II), Fe(II) and As(V) onto bacterially produced metal sulfide (BPMS) material was investigated using a batch equilibrium method. It was found that the sulfide material had adsorptive properties comparable with those of other adsorbents with respect to the specific uptake of a range of metals and, the levels to which dissolved metal concentrations in solution can be reduced. The percentage of adsorption increased with increasing pH and adsorbent dose, but decreased with increasing initial dissolved metal concentration. The pH of the solution was the most important parameter controlling adsorption of Cd(II), Cu(II), Fe(II), Ni(II), Pb(II), Zn(II), and As(V) by BPMS. The adsorption data were successfully modeled using the Langmuir adsorption isotherm. Desorption experiments showed that the reversibility of adsorption was low, suggesting high-affinity adsorption governed by chemisorption. The mechanism of adsorption for the divalent metals was thought to be the formation of strong, inner-sphere complexes involving surface hydroxyl groups. However, the mechanism for the adsorption of As(V) by BPMS appears to be distinct from that of surface hydroxyl exchange. These results have important implications to the management of metal sulfide sludge produced by bacterial sulfate reduction.
Physical properties of solar chromospheric plages. III - Models based on Ca II and Mg II observations

NASA Technical Reports Server (NTRS)

Kelch, W. L.; Linsky, J. L.

1978-01-01

Solar plages are modeled using observations of both the Ca II K and the Mg II h and k lines. A partial-redistribution approach is employed for calculating the line profiles on the basis of a grid of five model chromospheres. The computed integrated emission intensities for the five atmospheric models are compared with observations of six regions on the sun as well as with models of active-chromosphere stars. It is concluded that the basic plage model grid proposed by Shine and Linsky (1974) is still valid when the Mg II lines are included in the analysis and the Ca II and Mg II lines are analyzed using partial-redistribution diagnostics.
Diaquachloro-tris(ethyl-p-Aminobenzoate)copper(II) Chloride: Synthesis, Characterization and In Vitro Investigation of Antibacterial Activity

NASA Astrophysics Data System (ADS)

Rahardjo, S. B.; Lestari, W. W.; Syaima, H.

2017-07-01

The new complex of [Cu(benz)3(H2O)2Cl]Cl has been synthesized in 1:4 mole ratio of CuCl2·2H2O and ethyl-p-aminobenzoate (benz) in ethanol at room temperature. The complex was characterized by UV-Vis and infrared spectroscopy, Atomic Absorption Spectroscopy (AAS), thermal analysis, magnetic measurement and molar conductivity. Infrared spectra indicated that benz was coordinated to the metal ion through nitrogen of primary amine group. Water molecules and chloride ion were also coordinated to Cu(II). CuCl2·2H2O, benz, and Cu(II) complex were screened for investigating in vitro antibacterial activity against Staphylococcus aureus and Escherichia coli using a modified Kirby-Bauer method.
Carbonate-mediated Fe(II) oxidation in the air-cathode fuel cell: a kinetic model in terms of Fe(II) speciation.

PubMed

Song, Wei; Zhai, Lin-Feng; Cui, Yu-Zhi; Sun, Min; Jiang, Yuan

2013-06-06

Due to the high redox activity of Fe(II) and its abundance in natural waters, the electro-oxidation of Fe(II) can be found in many air-cathode fuel cell systems, such as acid mine drainage fuel cells and sediment microbial fuel cells. To deeply understand these iron-related systems, it is essential to elucidate the kinetics and mechanisms involved in the electro-oxidation of Fe(II). This work aims to develop a kinetic model that adequately describes the electro-oxidation process of Fe(II) in air-cathode fuel cells. The speciation of Fe(II) is incorporated into the model, and contributions of individual Fe(II) species to the overall Fe(II) oxidation rate are quantitatively evaluated. The results show that the kinetic model can accurately predict the electro-oxidation rate of Fe(II) in air-cathode fuel cells. FeCO3, Fe(OH)2, and Fe(CO3)2(2-) are the most important species determining the electro-oxidation kinetics of Fe(II). The Fe(II) oxidation rate is primarily controlled by the oxidation of FeCO3 species at low pH, whereas at high pH Fe(OH)2 and Fe(CO3)2(2-) are the dominant species. Solution pH, carbonate concentration, and solution salinity are able to influence the electro-oxidation kinetics of Fe(II) through changing both distribution and kinetic activity of Fe(II) species.
Human autoantibody to topoisomerase II.

PubMed

Hoffmann, A; Heck, M M; Bordwell, B J; Rothfield, N F; Earnshaw, W C

1989-02-01

The rheumatic diseases are characterized by the production of autoantibodies that are usually directed against components of the cell nucleus. In this communication, we describe autoantibodies that recognize DNA topoisomerase II (anti-topoII) present in the serum of a patient with systemic lupus erythematosus. Several lines of evidence indicate that this antibody recognizes topoisomerase II. First, it binds to the native enzyme in soluble extracts prepared from isolated chromosomes and effectively depletes such extracts of active enzyme. Second, the serum binds to topoisomerase II in immunoblots of mitotic chromosomes and chromosome scaffolds. Finally, the antiserum binds strongly to a fusion protein encoded by a cloned cDNA and expressed in Escherichia coli that (based on immunological evidence) represents the carboxy-terminal portion of chicken topoisomerase II. Autoantibodies such as the one described here may provide useful reagents for the study of human topoisomerase II.
Bioorthogonal Diversification of Peptides through Selective Ruthenium(II)-Catalyzed C-H Activation.

PubMed

Schischko, Alexandra; Ren, Hongjun; Kaplaneris, Nikolaos; Ackermann, Lutz

2017-02-01

Methods for the chemoselective modification of amino acids and peptides are powerful techniques in biomolecular chemistry. Among other applications, they enable the total synthesis of artificial peptides. In recent years, significant momentum has been gained by exploiting palladium-catalyzed cross-coupling for peptide modification. Despite major advances, the prefunctionalization elements on the coupling partners translate into undesired byproduct formation and lengthy synthetic operations. In sharp contrast, we herein illustrate the unprecedented use of versatile ruthenium(II)carboxylate catalysis for the step-economical late-stage diversification of α- and β-amino acids, as well as peptides, through chemo-selective C-H arylation under racemization-free reaction conditions. The ligand-accelerated C-H activation strategy proved water-tolerant and set the stage for direct fluorescence labelling as well as various modes of peptide ligation with excellent levels of positional selectivity in a bioorthogonal fashion. The synthetic utility of our approach is further demonstrated by twofold C-H arylations for the complexity-increasing assembly of artificial peptides within a multicatalytic C-H activation manifold. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Concurrent hippocampal induction of MHC II pathway components and glial activation with advanced aging is not correlated with cognitive impairment

PubMed Central

2011-01-01

Background Age-related cognitive dysfunction, including impairment of hippocampus-dependent spatial learning and memory, affects approximately half of the aged population. Induction of a variety of neuroinflammatory measures has been reported with brain aging but the relationship between neuroinflammation and cognitive decline with non-neurodegenerative, normative aging remains largely unexplored. This study sought to comprehensively investigate expression of the MHC II immune response pathway and glial activation in the hippocampus in the context of both aging and age-related cognitive decline. Methods Three independent cohorts of adult (12-13 months) and aged (26-28 months) F344xBN rats were behaviorally characterized by Morris water maze testing. Expression of MHC II pathway-associated genes identified by transcriptomic analysis as upregulated with advanced aging was quantified by qPCR in synaptosomal fractions derived from whole hippocampus and in hippocampal subregion dissections (CA1, CA3, and DG). Activation of astrocytes and microglia was assessed by GFAP and Iba1 protein expression, and by immunohistochemical visualization of GFAP and both CD74 (Ox6) and Iba1. Results We report a marked age-related induction of neuroinflammatory signaling transcripts (i.e., MHC II components, toll-like receptors, complement, and downstream signaling factors) throughout the hippocampus in all aged rats regardless of cognitive status. Astrocyte and microglial activation was evident in CA1, CA3 and DG of intact and impaired aged rat groups, in the absence of differences in total numbers of GFAP+ astrocytes or Iba1+ microglia. Both mild and moderate microglial activation was significantly increased in all three hippocampal subregions in aged cognitively intact and cognitively impaired rats compared to adults. Neither induction of MHCII pathway gene expression nor glial activation correlated to cognitive performance. Conclusions These data demonstrate a novel, coordinated age
Alamandine acts via MrgD to induce AMPK/NO activation against ANG II hypertrophy in cardiomyocytes.

PubMed

Jesus, Itamar Couto Guedes de; Scalzo, Sérgio; Alves, Fabiana; Marques, Kariny; Rocha-Resende, Cibele; Bader, Michael; Santos, Robson A Souza; Guatimosim, Silvia

2018-06-01

The renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of cardiovascular diseases. New members of this system have been characterized and shown to have biologically relevant actions. Alamandine and its receptor MrgD are recently identified components of RAS. In the cardiovascular system, alamandine actions included vasodilation, antihypertensive, and antifibrosis effects. Currently, the actions of alamandine on cardiomyocytes are unknown. Here our goal was twofold: 1) to unravel the signaling molecules activated by the alamandine/MrgD axis in cardiomyocytes; and 2) to evaluate the ability of this axis to prevent angiotensin II (ANG II)-induced hypertrophy. In cardiomyocytes from C57BL/6 mice, alamandine treatment induced an increase in nitric oxide (NO) production, which was blocked by d-Pro 7 -ANG-(1-7), a MrgD antagonist. This NO rise correlated with increased phosphorylation of AMPK. Alamandine-induced NO production was preserved in Mas -/- myocytes and lost in MrgD -/- cells. Binding of fluorescent-labeled alamandine was observed in wild-type cells, but it was dramatically reduced in MrgD -/- myocytes. We also assessed the consequences of prolonged alamandine exposure to cultured neonatal rat cardiomyocytes (NRCMs) treated with ANG II. Treatment of NRCMs with alamandine prevented ANG II-induced hypertrophy. Moreover, the antihypertrophic actions of alamandine were mediated via MrgD and NO, since they could be prevented by d-Pro 7 -ANG-(1-7) or inhibitors of NO synthase or AMPK. β-Alanine, a MrgD agonist, recapitulated alamandine's cardioprotective effects in cardiomyocytes. Our data show that alamandine via MrgD induces AMPK/NO signaling to counterregulate ANG II-induced hypertrophy. These findings highlight the therapeutic potential of the alamandine/MrgD axis in the heart.
High stability and biological activity of the copper(II) complexes of alloferon 1 analogues containing tryptophan.

PubMed

Kadej, Agnieszka; Kuczer, Mariola; Czarniewska, Elżbieta; Urbański, Arkadiusz; Rosiński, Grzegorz; Kowalik-Jankowska, Teresa

2016-10-01

Copper(II) complex formation processes between the alloferon 1 (Allo1) (HGVSGHGQHGVHG) analogues where the tryptophan residue is introducing in the place His residue H1W, H6W, H9W and H12W have been studied by potentiometric, UV-visible, CD and EPR spectroscopic, and MS methods. For all analogues of alloferon 1 complex speciation have been obtained for a 1:1 metal-to-ligand molar ratio and 2:1 of H1W because of precipitation at higher (2:1, 3:1 and 4:1) ratios. At physiological pH7.4 and a 1:1 metal-to-ligand molar ratio the tryptophan analogues of alloferon 1 form the CuH -1 L and/or CuH -2 L complexes with the 4N binding mode. The introduction of tryptophan in place of histidine residues changes the distribution diagram of the complexes formed with the change of pH and their stability constants compared to the respective substituted alanine analogues of alloferon 1. The CuH -1 L, CuH -2 L and CuH -3 L complexes of the tryptophan analogues are more stable from 1 to 5 log units in comparison to those of the alanine analogues. This stabilization of the complexes may result from cation(Cu(II))-π and indole/imidazole ring interactions. The induction of apoptosis in vivo, in Tenebrio molitor cells by the ligands and their copper(II) complexes at pH7.4 was studied. The biological results show that copper(II) ions in vivo did not cause any apparent apoptotic features. The most active were the H12W peptide and Cu(II)-H12W complex formed at pH7.4. Copyright © 2016 Elsevier Inc. All rights reserved.
Fibrinogen Vicenza and Genova II: two new cases of congenital dysfibrinogenemia with isolated defect of fibrin monomer polymerization and inhibitory activity on normal coagulation.

PubMed

Rodeghiero, F; Castaman, G C; Dal Belin Peruffo, A; Dini, E; Galletti, A; Barone, E; Gastaldi, G

1987-06-03

Two new cases of congenital dysfibrinogenemia are presented in which defective fibrin monomer polymerization and inhibitory activity on normal coagulation were observed. They have been tentatively called fibrinogen Vicenza and Genova II. The first was discovered in a family with mild bleeding diathesis, the second in an asymptomatic family. In almost all reported cases of fibrinogens with defective fibrin monomer polymerization, additional functional or structural defects have been detected. In our cases, on the contrary, detailed investigations failed to show any other abnormality. Fibrinogen Genova II is apparently identical to fibrinogen Baltimore IV, whereas fibrinogen Vicenza is similar to fibrinogen Troyes and Genova I, but also exerts an evident inhibitory activity on normal coagulation and differs from fibrinogen Genova II and Baltimore IV showing a different kinetic pattern of fibrin monomer polymerization.
Potentiated virucidal activity of pomegranate rind extract (PRE) and punicalagin against Herpes simplex virus (HSV) when co-administered with zinc (II) ions, and antiviral activity of PRE against HSV and aciclovir-resistant HSV

PubMed Central

Houston, David M. J.; Bugert, Joachim J.; Denyer, Stephen P.

2017-01-01

Background There is a clinical need for new therapeutic products against Herpes simplex virus (HSV). The pomegranate, fruit of the tree Punica granatum L, has since ancient times been linked to activity against infection. This work probed the activity of pomegranate rind extract (PRE) and co-administered zinc (II) ions. Materials and methods PRE was used in conjunction with zinc (II) salts to challenge HSV-1 and aciclovir-resistant HSV in terms of virucidal plaque assay reduction and antiviral activities in epithelial Vero host cells. Cytotoxicity was determined by the MTS assay using a commercial kit. Results Zinc sulphate, zinc citrate, zinc stearate and zinc gluconate demonstrated similar potentiated virucidal activity with PRE against HSV-1 by up to 4-fold. A generally parabolic relationship was observed when HSV-1 was challenged with PRE and varying concentrations of ZnSO4, with a maximum potentiation factor of 5.5. Punicalagin had 8-fold greater virucidal activity than an equivalent mass of PRE. However, antiviral data showed that punicalagin had significantly lower antiviral activity compared to the activity of PRE (EC50 = 0.56 μg mL-1) a value comparable to aciclovir (EC50 = 0.18 μg mL-1); however, PRE also demonstrated potency against aciclovir-resistant HSV (EC50 = 0.02 μg mL-1), whereas aciclovir showed no activity. Antiviral action of PRE was not influenced by ZnSO4. No cytotoxicity was detected with any test solution. Conclusions The potentiated virucidal activity of PRE by coadministered zinc (II) has potential as a multi-action novel topical therapeutic agent against HSV infections, such as coldsores. PMID:28665969
Thermodynamic Analysis of Nickel(II) and Zinc(II) Adsorption to Biochar.

PubMed

Alam, Md Samrat; Gorman-Lewis, Drew; Chen, Ning; Flynn, Shannon L; Ok, Yong Sik; Konhauser, Kurt O; Alessi, Daniel S

2018-05-21

While numerous studies have investigated metal uptake from solution by biochar, few of these have developed a mechanistic understanding of the adsorption reactions that occur at the biochar surface. In this study, we explore a combined modeling and spectroscopic approach for the first time to describe the molecular level adsorption of Ni(II) and Zn(II) to five types of biochar. Following thorough characterization, potentiometric titrations were carried out to measure the proton (H + ) reactivity of each biochar, and the data was used to develop protonation models. Surface complexation modeling (SCM) supported by synchrotron-based extended X-ray absorption fine structure (EXAFS) was then used to gain insights into the molecular scale metal-biochar surface reactions. The SCM approach was combined with isothermal titration calorimetry (ITC) data to determine the thermodynamic driving forces of metal adsorption. Our results show that the reactivity of biochar toward Ni(II) and Zn(II) directly relates to the site densities of biochar. EXAFS along with FT-IR analyses, suggest that Ni(II) and Zn(II) adsorption occurred primarily through proton-active carboxyl (-COOH) and hydroxyl (-OH) functional groups on the biochar surface. SCM-ITC analyses revealed that the enthalpies of protonation are exothermic and Ni(II) and Zn(II) complexes with biochar surface are slightly exothermic to slightly endothermic. The results obtained from these combined approaches contribute to the better understanding of molecular scale metal adsorption onto the biochar surface, and will facilitate the further development of thermodynamics-based, predictive approaches to biochar removal of metals from contaminated water.
Activation of D4 dopamine receptor decreases AT1 angiotensin II receptor expression in rat renal proximal tubule cells

PubMed Central

Chen, Ken; Deng, Kun; Wang, Xiaoyan; Wang, Zhen; Zheng, Shuo; Ren, Hongmei; He, Duofen; Han, Yu; Asico, Laureano D.; Jose, Pedro A.; Zeng, Chunyu

2014-01-01

The dopaminergic and renin angiotensin systems interact to regulate blood pressure. Disruption of the D4 dopamine receptor gene in mice produces hypertension that is associated with increased renal AT1 receptor expression. We hypothesize that the D4 receptor can inhibit AT1 receptor expression and function in renal proximal tubules (RPTs) cells from Wistar-Kyoto (WKY) rats but the D4 receptor regulation of AT1 receptor is aberrant in RPT cells from spontaneously hypertensive rats (SHRs). The D4 receptor agonist, PD168077, decreased AT1 receptor protein expression in a time and concentration-dependent manner in WKY cells. By contrast, in SHR cells, PD168077 increased AT1 receptor protein expression. The inhibitory effect of D4 receptor on AT1 receptor expression in WKY cells was blocked by a calcium channel blocker, nicardipine, or calcium-free medium, indicating that calcium is involved in the D4 receptor-mediated signaling pathway. Angiotensin II increased Na+-K+ ATPase activity in WKY cells. Pretreatment with PD168077 decreased the stimulatory effect of angiotensin II on Na+-K+ ATPase activity in WKY cells. In SHR cells, the inhibitory effect of D4 receptor on angiotensin II-mediated stimulation of Na+-K+ ATPase activity was aberrant; pretreatment with PD168077 augmented the stimulatory effect of AT1 receptor on Na+-K+ ATPase activity in SHR cells. This was confirmed in vivo; pre-treatment with PD128077 for one week augmented the anti-hypertensive and natriuretic effect of losartan in SHRs but not in WKY rats. We suggest that an aberrant interaction between D4 and AT1 receptors may play a role in the abnormal regulation of sodium excretion in hypertension. PMID:25368031
DNA cleavage, antibacterial, antifungal and anthelmintic studies of Co(II), Ni(II) and Cu(II) complexes of coumarin Schiff bases: Synthesis and spectral approach

NASA Astrophysics Data System (ADS)

Patil, Sangamesh A.; Prabhakara, Chetan T.; Halasangi, Bhimashankar M.; Toragalmath, Shivakumar S.; Badami, Prema S.

2015-02-01

The metal complexes of Co(II), Ni(II) and Cu(II) have been synthesized from 6-formyl-7,8-dihydroxy-4-methylcoumarin with o-toluidine/3-aminobenzotrifluoride. The synthesized Schiff bases and their metal complexes were structurally characterized based on IR, 1H NMR, 13C NMR, UV-visible, ESR, magnetic, thermal, fluorescence, mass and ESI-MS studies. The molar conductance values indicate that complexes are non-electrolytic in nature. Elemental analysis reveals ML2·2H2O [M = Co(II), Ni(II) and Cu(II)] stoichiometry, where 'L' stands for a singly deprotonated ligand. The presence of co-ordinated water molecules were confirmed by thermal studies. The spectroscopic studies suggest the octahedral geometry. Redox behavior of the complexes were confirmed by cyclic voltammetry. All the synthesized compounds were screened for their antibacterial (Escherichia coli, Pseudomonas auregenosa, klebsiella, Proteus, Staphylococcus aureus and salmonella) antifungal (Candida, Aspergillus niger and Rhizopus), anthelmintic (Pheretima posthuma) and DNA cleavage (Calf Thymus DNA) activity.
Characterization and cloning of tripeptidyl peptidase II from the fruit fly, Drosophila melanogaster.

PubMed

Renn, S C; Tomkinson, B; Taghert, P H

1998-07-24

We describe the characterization, cloning, and genetic analysis of tripeptidyl peptidase II (TPP II) from Drosophila melanogaster. Mammalian TPP II removes N-terminal tripeptides, has wide distribution, and has been identified as the cholecystokinin-degrading peptidase in rat brain. Size exclusion and ion exchange chromatography produced a 70-fold purification of dTPP II activity from Drosophila tissue extracts. The substrate specificity and the inhibitor sensitivity of dTPP II is comparable to that of the human enzyme. In particular, dTPP II is sensitive to butabindide, a specific inhibitor of the rat cholecystokinin-inactivating activity. We isolated a 4309-base pair dTPP II cDNA which predicts a 1354-amino acid protein. The deduced human and Drosophila TPP II proteins display 38% overall identity. The catalytic triad, its spacing, and the sequences that surround it are highly conserved; the C-terminal end of dTPP II contains a 100-amino acid insert not found in the mammalian proteins. Recombinant dTPP II displays the predicted activity following expression in HEK cells. TPP II maps to cytological position 49F4-7; animals deficient for this interval show reduced TPP II activity.
Removal of Pb(II) from water by the activated carbon modified by nitric acid under microwave heating.

PubMed

Yao, Shuheng; Zhang, Jiajun; Shen, Dekui; Xiao, Rui; Gu, Sai; Zhao, Ming; Liang, Junyu

2016-02-01

The rice husk based activated carbon (RH-AC) was treated by nitric acid under microwave heating, in order to improve its capability for the removal of heavy metal ions from water. The optimal conditions for the modification of RH-AC (M-RH-AC) were determined by means of orthogonal array experimental design, giving those as the concentration of nitric acid of 8mol/L, modification time of 15min, modification temperature of 130°C and microwave power of 800W. The characteristics of the M-RH-AC and RH-AC were examined by BET, XRD, Raman spectrum, pH titration, zeta potential, Boehm titration and FTIR analysis. The M-RH-AC has lower pore surface area, smaller crystallite, lower pHIEP and more oxygen-containing functional groups than the RH-AC. Removal capacity of Pb(II) ions by the M-RH-AC and RH-AC from water solution was estimated concerning the influence of contact time, pH value, and initial concentration. The equilibrium time of Pb(II) removal was found to be around 90min after modification process. Two kinetic models are adopted to describe the possible Pb(II) adsorption mechanism, finding that the adsorption rate of Pb(II) ions by the M-RH-AC is larger than that of RH-AC. Copyright © 2015 Elsevier Inc. All rights reserved.
α2-Macroglobulin Capture Allows Detection of Mast Cell Chymase in Serum and Creates a Circulating Reservoir of Angiotensin II-generating Activity1

PubMed Central

Raymond, Wilfred W.; Su, Sharon; Makarova, Anastasia; Wilson, Todd M.; Carter, Melody C.; Metcalfe, Dean D.; Caughey, George H.

2009-01-01

Human chymase is a highly efficient angiotensin II-generating serine peptidase expressed by the MCTC subset of mast cells. When secreted from degranulating cells, it can interact with a variety of circulating anti-peptidases, but is mostly captured by α2-macroglobulin, which sequesters peptidases in a cage-like structure that precludes interactions with large protein substrates and inhibitors, like serpins. The present work shows that α2-macroglobulin-bound chymase remains accessible to small substrates, including angiotensin I, with activity in serum that is stable with prolonged incubation. We used α2-macroglobulin capture to develop a sensitive, microtiter plate-based assay for serum chymase, assisted by a novel substrate synthesized based on results of combinatorial screening of peptide substrates. The substrate has low background hydrolysis in serum and is chymase-selective, with minimal cleavage by the chymotryptic peptidases cathepsin G and chymotrypsin. The assay detects activity in chymase-spiked serum with a threshold of ~1 pM (30 pg/ml), and reveals native chymase activity in serum of most subjects with systemic mastocytosis. α2-Macroglobulin-bound chymase generates angiotensin II in chymase-spiked serum, and appears in native serum as chymostatin-inhibited activity, which can exceed activity of captopril-sensitive angiotensin converting enzyme. These findings suggest that chymase bound to α2-macroglobulin is active, that the circulating complex is an angiotensin-converting enzyme inhibitor-resistant reservoir of angiotensin II-generating activity, and that α2-macroglobulin capture may be exploited in assessing systemic release of secreted peptidases. PMID:19380825

Signalling pathway involved in nitric oxide synthase type II activation in chondrocytes: synergistic effect of leptin with interleukin-1

PubMed Central

Otero, Miguel; Lago, Rocío; Lago, Francisca; Reino, Juan Jesús Gomez; Gualillo, Oreste

2005-01-01

The objective of the present study was to investigate the effect of leptin, alone or in combination with IL-1, on nitric oxide synthase (NOS) type II activity in vitro in human primary chondrocytes, in the mouse chondrogenic ATDC5 cell line, and in mature and hypertrophic ATDC5 differentiated chondrocytes. For completeness, we also investigated the signalling pathway of the putative synergism between leptin and IL-1. For this purpose, nitric oxide production was evaluated using the Griess colorimetric reaction in culture medium of cells stimulated over 48 hours with leptin (800 nmol/l) and IL-1 (0.025 ng/ml), alone or combined. Specific pharmacological inhibitors of NOS type II (aminoguanidine [1 mmol/l]), janus kinase (JAK)2 (tyrphostin AG490 and Tkip), phosphatidylinositol 3-kinase (PI3K; wortmannin [1, 2.5, 5 and 10 μmol/l] and LY294002 [1, 2.5, 5 and 10 μmol/l]), mitogen-activated protein kinase kinase (MEK)1 (PD098059 [1, 5, 10, 20 and 30 μmol/l]) and p38 kinase (SB203580 [1, 5, 10, 20 and 30 μmol/l]) were added 1 hour before stimulation. Nitric oxide synthase type II mRNA expression in ATDC5 chondrocytes was investigated by real-time PCR and NOS II protein expression was analyzed by western blot. Our results indicate that stimulation of chondrocytes with IL-1 results in dose-dependent nitric oxide production. In contrast, leptin alone was unable to induce nitric oxide production or expression of NOS type II mRNA or its protein. However, co-stimulation with leptin and IL-1 resulted in a net increase in nitric oxide concentration over IL-1 challenge that was eliminated by pretreatment with the NOS II specific inhibitor aminoguanidine. Pretreatment with tyrphostin AG490 and Tkip (a SOCS-1 mimetic peptide that inhibits JAK2) blocked nitric oxide production induced by leptin/IL-1. Finally, wortmannin, LY294002, PD098059 and SB203580 significantly decreased nitric oxide production. These findings were confirmed in mature and hypertrophic ATDC5 chondrocytes, and
Zinc(II) complexes with potent cyclin-dependent kinase inhibitors derived from 6-benzylaminopurine: synthesis, characterization, X-ray structures and biological activity.

PubMed

Trávnícek, Zdenek; Krystof, Vladimír; Sipl, Michal

2006-02-01

The synthesis, characterization and biological activity of the first zinc(II) complexes with potent inhibitors of cyclin-dependent kinases (CDKs) derived from 6-benzylaminopurine are described. Based on the results following from elemental analyses, infrared, NMR and ES+MS (electrospray mass spectra in the positive ion mode) spectroscopies, conductivity data, thermal analysis and X-ray structures, the tetrahedral Zn(II) complexes of the compositions [Zn(Olo)Cl(2)](n) (1), [Zn(iprOlo)Cl(2)](n) (2), [Zn(BohH(+))Cl(3)] x H(2)O (3) and [Zn(iprOloH(+))Cl(3)] x H(2)O (4) have been prepared, where Olo=2-(2-hydroxyethylamino)-6-benzylamino-9-methylpurine (Olomoucine), iprOlo=2-(2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (i-propyl-Olomoucine), Boh=2-(3-hydroxypropylamino)-6-benzylamino-9-isopropylpurine (Bohemine). The 1D-polymeric chain structure for [Zn(Olo)Cl(2)](n) (1) as well as the monomeric one for [Zn(BohH(+))Cl(3)] x H(2)O (3) and [Zn(iprOloH(+))Cl(3)] x H(2)O (4) have been revealed unambiguously by single crystal X-ray analyses. The 1D-polymeric chain of 1 consists of Zn(Olo)Cl(2) monomeric units in which the Zn(II) ion is coordinated by two chlorine atoms and one oxygen atom of the 2-hydroxyethylamino group of Olomoucine. The next monomeric unit is bonded to Zn(II) through the N7 atom of a purine ring. Thus, each of Zn(II) ions is tetrahedrally coordinated and a ZnCl(2)NO chromophore occurs in the complex 1. The complexes 3 and 4 are mononuclear species with a distorted tetrahedral arrangement of donor atoms around the Zn(II) ion with a ZnCl(3)N chromophore. The corresponding CDK inhibitor, i.e., both Boh and iprOlo, is coordinated to Zn(II) via the N7 atom of the purine ring in 3 and 4. The cytotoxicity of the zinc(II) complexes against human melanoma, sarcoma, leukaemia and carcinoma cell lines has been determined as well as the inhibition of the CDK2/cyclin E kinase. A relationship between the structure and biological activity of the complexes is
Surgery in World War II. Orthopedic Surgery in the Zone of Interior

DTIC Science & Technology

1970-01-01

General Reference and Research Branch ROSE C. ENGELMAN, Ph. D., Chief, Historians Branch GERALDINE B. SITES, Chief, Information Activities Branch Major...SERIES Internal Medicine in World War II: Vol. I. Activities of Medical Consultants Vol. II. Infectious Diseases Vol. III. Infectious Diseases and General...Arthropodborne Diseases Other Than Malaria Vol. IX. Special Fields Surgery in World War II: Activities of Surgical Consultants, vol. I Activities of Surgical
Synthesis, characterization, and biological activity of some novel Schiff bases and their Co(II) and Ni(II) complexes: A new route for Co3O4 and NiO nanoparticles for photocatalytic degradation of methylene blue dye

NASA Astrophysics Data System (ADS)

Nassar, Mostafa Y.; Aly, Hisham M.; Abdelrahman, Ehab A.; Moustafa, Moustafa E.

2017-09-01

Six novel Co(II) and Ni(II)-triazole Schiff base complexes have been successfully synthesized by refluxing the prepared triazole Schiff bases with CoCl2·6H2O or NiCl2·6H2O. The Schiff base ligands were prepared through condensation of 3-R-4-amino-5-hydrazino-1,2,4-triazole with dibenzoylmethane [Rdbnd H, CH3, and CH2CH3; namely, L1, L2, and L3, respectively]. The prepared Co(II) and Ni(II) complexes have been identified using elemental analysis, FT-IR, UV-Vis, magnetic moment, conductivity, and thermal analysis. On the basis of the conductance results, it was concluded that all the prepared complexes are nonelectrolytes. Interestingly, the prepared Co(II) and Ni(II) complexes were employed as precursors for producing of Co3O4 and NiO nanoparticles, respectively. The produced nanostructures have been identified by XRD, HR-TEM, FT-IR and UV-Vis spectra. The produced nanoparticles revealed good photocatalytic activity for the degradation of methylene blue dye under UV illumination in presence of hydrogen peroxide. The percent of degradation was estimated to be 55.71% in 420.0 min and 90.43% in 360.0 min for Co3O4 and NiO, respectively. Moreover, the synthesized complexes, nano-sized Co3O4, and NiO products have been examined, employing modified Bauer- Kirby method, for antifungal (Candida albicans and Aspergillus flavus) and antibacterial (Staphylococcus aureus and Escherichia coli) activities.
Ama1p-activated anaphase-promoting complex regulates the destruction of Cdc20p during meiosis II

PubMed Central

Tan, Grace S.; Magurno, Jennifer; Cooper, Katrina F.

2011-01-01

The execution of meiotic divisions in Saccharomyces cerevisiae is regulated by anaphase-promoting complex/cyclosome (APC/C)–mediated protein degradation. During meiosis, the APC/C is activated by association with Cdc20p or the meiosis-specific activator Ama1p. We present evidence that, as cells exit from meiosis II, APC/CAma1 mediates Cdc20p destruction. APC/CAma1 recognizes two degrons on Cdc20p, the destruction box and destruction degron, with either domain being sufficient to mediate Cdc20p destruction. Cdc20p does not need to associate with the APC/C to bind Ama1p or be destroyed. Coimmunoprecipitation analyses showed that the diverged amino-terminal region of Ama1p recognizes both Cdc20p and Clb1p, a previously identified substrate of APC/CAma1. Domain swap experiments revealed that the C-terminal WD region of Cdh1p, when fused to the N-terminal region of Ama1p, could direct most of Ama1p functions, although at a reduced level. In addition, this fusion protein cannot complement the spore wall defect in ama1Δ strains, indicating that substrate specificity is also derived from the WD repeat domain. These findings provide a mechanism to temporally down-regulate APC/CCdc20 activity as the cells complete meiosis II and form spores. PMID:21118994
Removal of lead(II) by adsorption using treated granular activated carbon: batch and column studies.

PubMed

Goel, Jyotsna; Kadirvelu, Krishna; Rajagopal, Chitra; Kumar Garg, Vinod

2005-10-17

In the present study, a deeper understanding of adsorption behavior of Pb(II) from aqueous systems onto activated carbon and treated activated carbon has been attempted via static and column mode studies under various conditions. It probes mainly two adsorbents that is, activated carbon (AC) and modified activated carbon (AC-S). Characterization of both the adsorbents was one of the key focal areas of the present study. This has shown a clear change or demarcation in the various physical and chemical properties of the modified adsorbent from its precursor activated carbon. Both the adsorbents are subjected to static mode adsorption studies and then after a comparison based on isotherm analysis; more efficient adsorbent is screened for column mode adsorption studies. The lead removal increased for sample of treated carbon. The extent of Pb(II) removal was found to be higher in the treated activated carbon. The aim of carrying out the continuous-flow studies was to assess the effect of various process variables, viz., of bed height, hydraulic loading rate and initial feed concentration on breakthrough time and adsorption capacity. This has helped in ascertaining the practical applicability of the adsorbent. Breakthrough curves were plotted for the adsorption of lead on the adsorbent using continuous-flow column operation by varying different operating parameters like hydraulic loading rate (3.0-10.5 m3/(hm2)), bed height (0.3-0.5 m) and feed concentrations (2.0-6.0 mg/l). At the end, an attempt has also been made to model the data generated from column studies using the empirical relationship based on Bohart-Adams model. This model has provided an objective framework to the subjective interpretation of the adsorption system and the model constant obtained here can be used to achieve the ultimate objective of our study that is, up scaling and designing of adsorption process at the pilot plant scale level. AC-S column regeneration using 0.5 and 1.0M concentration of
New Rh 2 (II,II) Architecture for the Catalytic Reduction of H +

DOE PAGES

White, Travis A.; Witt, Suzanne E.; Li, Zhanyong; ...

2015-09-25

Formamidinate-bridged Rh 2 II,II complexes containing diimine ligands of the formula cis-[Rh 2 II,II(μ-DTolF) 2(NN) 2] 2+ (Rh 2-NN 2), where DTolF = p-ditolylformamidinate and NN = dppn (benzo[i]dipyrido[3,2-a:2',3'-h]quinoxaline), dppz (dipyrido[3,2-a:2',3'-c]phenazine), and phen (1,10-phenanthroline), electrocatalytically reduce H + to H 2 in DMF solutions containing CH 3COOH at a glassy carbon electrode. Cathodic scans in the absence of acid display a Rh III,II/II,II reduction at -0.90 V vs Fc +/Fc followed by NN 0/– reduction at -1.13, -1.36, and -1.65 V for Rh 2-dppn 2, Rh 2-dppz 2, and Rh 2-phen 2, respectively. Upon the addition of acid, Rh 2-dppnmore » 2 and Rh 2-dppz 2 undergo reduction–protonation–reduction at each pyrazine-containing NN ligand prior to the Rh 2 II,II/II,I reduction. The Rh 2 II,I species is thus protonated at one of the metal centers, resulting in the formation of the corresponding Rh 2 II,III-hydride. In the case of Rh 2-phen 2, the reduction of the phen ligand is followed by intramolecular electron transfer to the Rh 2 II,II core in the presence of protons to form a Rh 2 II,III-hydride species. Further reduction and protonation at the Rh 2 core for all three complexes rapidly catalyzes H 2 formation with varied calculated turnover frequencies (TOF) and overpotential values (η): 2.6 × 10 4 s –1 and 0.56 V for Rh 2-dppn, 2.8 × 10 4 s –1 and 0.50 V for Rh 2-dppz 2, and 5.9 × 10 4 s –1 and 0.64 V for Rh 2-phen 2. Bulk electrolysis confirmed H 2 formation, and further CH 3COOH addition regenerates H 2 production, attesting to the robust nature of the architecture. The cis-[Rh 2 II,II(μ-DTolF) 2(NN) 2] 2+ architecture benefits by combining electron-rich formamidinate bridges, a redox-active Rh 2 II,II core, and electron-accepting NN diimine ligands to allow for the electrocatalysis of H + substrate to H 2 fuel.« less
Regulation of glutamine synthetase II activity in Rhizobium meliloti 104A14.

PubMed Central

Shatters, R G; Somerville, J E; Kahn, M L

1989-01-01

Most rhizobia contain two glutamine synthetase (GS) enzymes: GSI, encoded by glnA, and GSII, encoded by glnII. We have found that WSU414, a Rhizobium meliloti 104A14 glutamine auxotroph derived from a glnA parental strain, is an ntrA mutant. The R. meliloti glnII promoter region contains DNA sequences similar to those found in front of other genes that require ntrA for their transcription. No GSII was found in the glnA ntrA mutant, and when a translational fusion of glnII to the Escherichia coli lacZ gene was introduced into WSU414, no beta-galactosidase was expressed. These results indicate that ntrA is required for glnII expression. The ntrA mutation did not prevent the expression of GSI. In free-living culture, the level of GSII and of the glnII-lacZ fusion protein was regulated by altering transcription in response to available nitrogen. No GSII protein was detected in alfalfa, pea, or soybean nodules when anti-GSII-specific antiserum was used. Images PMID:2570059
New platinum (II) and palladium (II) complexes of coumarin-thiazole Schiff base with a fluorescent chemosensor properties: Synthesis, spectroscopic characterization, X-ray structure determination, in vitro anticancer activity on various human carcinoma cell lines and computational studies.

PubMed

Şahin, Ömer; Özdemir, Ümmühan Özmen; Seferoğlu, Nurgül; Genc, Zuhal Karagöz; Kaya, Kerem; Aydıner, Burcu; Tekin, Suat; Seferoğlu, Zeynel

2018-01-01

A new coumarin-thiazole based Schiff base (Ligand, L) and its Pd(II), Pt(II) complexes; ([Pd(L) 2 ] and [Pt(L) 2 ]), were synthesized and characterized using spectrophotometric techniques (NMR, IR, UV-vis, LC-MS), magnetic moment, and conductivity measurements. A single crystal X-ray analysis for only L was done. The crystals of L have monoclinic crystal system and P21/c space group. To gain insight into the structure of L and its complexes, we used density functional theory (DFT) method to optimize the molecules. The photophysical properties changes were observed after deprotonation of L with CN - via intermolecular charge transfer (ICT). Additionally, as the sensor is a colorimetric and fluorimetric cyanide probe containing active sites such as coumarin-thiazole and imine (CH=N), it showed fast color change from yellow to deep red in the visible region, and yellow fluorescence after CN - addition to the imine bond, in DMSO. The reaction mechanisms of L with CN - , F - and AcO - ions were evaluated using 1 H NMR shifts. The results showed that, the reaction of L with CN - ion was due to the deprotonation and addition mechanisms at the same time. The anti-cancer activity of L and its Pd(II) and Pt(II) complexes were evaluated in vitro using MTT assay on the human cancer lines MCF-7 (human breast adenocarcinoma), LS174T (human colon carcinoma), and LNCAP (human prostate adenocarcinoma). The anti-cancer effects of L and its complexes, on human cells, were determined by comparing the half maximal inhibitory concentration (IC 50 ) values. The activity results showed that, the Pd(II) complex of L has higher anti-tumor effect than L and its Pt(II) complex against the tested human breast adenocarcinoma (MCF-7), human prostate adenocarcinoma (LNCAP), and human colon carcinoma (LS174T) cell lines. Copyright © 2017 Elsevier B.V. All rights reserved.
Identification and Characterization of Novel Immunomodulatory Bursal-derived Pentapeptide-II (BPP-II)*

PubMed Central

Feng, Xiu-Li; Liu, Qing-Tao; Cao, Rui-Bing; Zhou, Bin; Ma, Zhi-Yong; Deng, Wen-Lei; Wei, Jian-Chao; Qiu, Ya-Feng; Wang, Fang-Quan; Gu, Jin-Yan; Wang, Feng-Juan; Zheng, Qi-Sheng; Ishag, Hassan; Chen, Pu-Yan

2012-01-01

The bursa of Fabricius, the acknowledged central humoral immune organ, plays a vital role in B lymphocyte differentiation. However, there are few reports of the molecular basis of the mechanism on immune induction and potential antitumor activity of bursal-derived peptides. In this paper, a novel bursal-derived pentapeptide-II (BPP-II, MTLTG) was isolated and exerted immunomodulatory functions on antibody responses in vitro. Gene microarray analyses demonstrated that BPP-II regulated expression of 2478 genes in a mouse-derived hybridoma cell line. Immune-related gene ontology functional procedures were employed for further functional analysis. Furthermore, the majority of BPP-II-regulated pathways were associated with immune responses and tumor processes. Moreover, BPP-II exhibited immunomodulatory effects on antigen-specific immune responses in vivo, including enhancement of avian influenza virus (H9N2 subtype)-specific antibody and cytokine production and modification of T cell immunophenotypes and lymphocyte proliferation. Finally, BPP-II triggered p53 expression and stabilization and selectively inhibited tumor cell proliferation. These data identified the multifunctional factor, BPP-II, as a novel biomaterial representing an important linking between the humoral central immune system and immune induction, including antitumor. Information generated in this study elucidates further the mechanisms involved in humoral immune system and represents the potential basis of effective immunotherapeutic strategies for treating human tumors and immune improvement. PMID:22184121
Identification and characterization of novel immunomodulatory bursal-derived pentapeptide-II (BPP-II).

PubMed

Feng, Xiu-Li; Liu, Qing-Tao; Cao, Rui-Bing; Zhou, Bin; Ma, Zhi-Yong; Deng, Wen-Lei; Wei, Jian-Chao; Qiu, Ya-Feng; Wang, Fang-Quan; Gu, Jin-Yan; Wang, Feng-Juan; Zheng, Qi-Sheng; Ishag, Hassan; Chen, Pu-Yan

2012-02-03

The bursa of Fabricius, the acknowledged central humoral immune organ, plays a vital role in B lymphocyte differentiation. However, there are few reports of the molecular basis of the mechanism on immune induction and potential antitumor activity of bursal-derived peptides. In this paper, a novel bursal-derived pentapeptide-II (BPP-II, MTLTG) was isolated and exerted immunomodulatory functions on antibody responses in vitro. Gene microarray analyses demonstrated that BPP-II regulated expression of 2478 genes in a mouse-derived hybridoma cell line. Immune-related gene ontology functional procedures were employed for further functional analysis. Furthermore, the majority of BPP-II-regulated pathways were associated with immune responses and tumor processes. Moreover, BPP-II exhibited immunomodulatory effects on antigen-specific immune responses in vivo, including enhancement of avian influenza virus (H9N2 subtype)-specific antibody and cytokine production and modification of T cell immunophenotypes and lymphocyte proliferation. Finally, BPP-II triggered p53 expression and stabilization and selectively inhibited tumor cell proliferation. These data identified the multifunctional factor, BPP-II, as a novel biomaterial representing an important linking between the humoral central immune system and immune induction, including antitumor. Information generated in this study elucidates further the mechanisms involved in humoral immune system and represents the potential basis of effective immunotherapeutic strategies for treating human tumors and immune improvement.
Biology II Curriculum Guide. Bulletin 1820.

ERIC Educational Resources Information Center

Louisiana State Dept. of Education, Baton Rouge. Div. of Academic Programs.

In 1986, the Louisiana State Board of Elementary and Secondary Education requested that an advanced course in Biology II be developed. The resulting curriculum guide contains grade appropriate goals, skills, and competencies; suggested activities; suggested materials of instruction; and minimum time allotments for instruction. Biology II is a…
Synthesis, characterization, DFT calculations and antibacterial activity of palladium(II) cyanide complexes with thioamides

NASA Astrophysics Data System (ADS)

Ahmad, Saeed; Nadeem, Shafqat; Anwar, Aneela; Hameed, Abdul; Tirmizi, Syed Ahmed; Zierkiewicz, Wiktor; Abbas, Azhar; Isab, Anvarhusein A.; Alotaibi, Mshari A.

2017-08-01

Palladium(II) cyanide complexes of thioamides (or thiones) having the general formula PdL2(CN)2, where L = Thiourea (Tu), Methylthiourea (Metu), N,N‧-Dimethylthiourea (Dmtu), Tetramethylthiourea (Tmtu), 2-Mercaptopyridine (Mpy) and 2-Mercaptopyrimidine (Mpm) were prepared by reacting K2[PdCl4] with potassium cyanide and thioamides in the molar ratio of 1:2:2. The complexes were characterized by elemental analysis, thermal and spectroscopic methods (IR, 1H and 13C NMR). The structures of three of the complexes were predicted by DFT calculations. The appearance of a band around 2100 cm-1 in IR and resonances around 120-130 ppm in the 13C NMR spectra indicated the coordination of cyanide to palladium(II). More than one resonances were observed for CN- carbon atoms in 13C NMR indicating the existence of equilibrium between different species in solution. DFT calculations revealed that in the case of the palladium(II) complex of Tmtu, the ionic dinuclear [Pd(Tmtu)4][Pd(CN)4] form was more stable than the dimer of mononuclear complex [Pd(Tmtu)2(CN)2] by 0.91 kcal mol-1, while for the complexes of Tu or Mpy ligands, the nonionic [Pd(L)2(CN)2] forms were more stable than the corresponding [Pd(L)4][Pd(CN)4] complexes by 1.26 and 6.49 kcal mol-1 for L = Tu and Mpy, respectively. The complexes were screened for antibacterial effects and some of them showed significant activities against both gram positive as well as gram negative bacteria.
A series of tetraazalene radical-bridged M2 (M = CrIII, MnII, FeII, CoII) complexes with strong magnetic exchange coupling.

PubMed

DeGayner, Jordan A; Jeon, Ie-Rang; Harris, T David

2015-11-13

The ability of tetraazalene radical bridging ligands to mediate exceptionally strong magnetic exchange coupling across a range of transition metal complexes is demonstrated. The redox-active bridging ligand N , N ', N '', N '''-tetra(2-methylphenyl)-2,5-diamino-1,4-diiminobenzoquinone ( NMePh LH 2 ) was metalated to give the series of dinuclear complexes [(TPyA) 2 M 2 ( NMePh L 2- )] 2+ (TPyA = tris(2-pyridylmethyl)amine, M = Mn II , Fe II , Co II ). Variable-temperature dc magnetic susceptibility data for these complexes reveal the presence of weak superexchange interactions between metal centers, and fits to the data provide coupling constants of J = -1.64(1) and -2.16(2) cm -1 for M = Mn II and Fe II , respectively. One-electron reduction of the complexes affords the reduced analogues [(TPyA) 2 M 2 ( NMePh L 3- ˙)] + . Following a slightly different synthetic procedure, the related complex [(TPyA) 2 CrIII2( NMePh L 3- ˙)] 3+ was obtained. X-ray diffraction, cyclic voltammetry, and Mössbauer spectroscopy indicate the presence of radical NMePh L 3- ˙ bridging ligands in these complexes. Variable-temperature dc magnetic susceptibility data of the radical-bridged species reveal the presence of strong magnetic interactions between metal centers and ligand radicals, with simulations to data providing exchange constants of J = -626(7), -157(7), -307(9), and -396(16) cm -1 for M = Cr III , Mn II , Fe II , and Co II , respectively. Moreover, the strength of magnetic exchange in the radical-bridged complexes increases linearly with decreasing M-L bond distance in the oxidized analogues. Finally, ac magnetic susceptibility measurements reveal that [(TPyA) 2 Fe 2 ( NMePh L 3- ˙)] + behaves as a single-molecule magnet with a relaxation barrier of U eff = 52(1) cm -1 . These results highlight the ability of redox-active tetraazalene bridging ligands to enable dramatic enhancement of magnetic exchange coupling upon redox chemistry and provide a rare opportunity to examine
Effects of early activator treatment in patients with class II malocclusion evaluated by thin-plate spline analysis.

PubMed

Lux, C J; Rübel, J; Starke, J; Conradt, C; Stellzig, P A; Komposch, P G

2001-04-01

The aim of the present longitudinal cephalometric study was to evaluate the dentofacial shape changes induced by activator treatment between 9.5 and 11.5 years in male Class II patients. For a rigorous morphometric analysis, a thin-plate spline analysis was performed to assess and visualize dental and skeletal craniofacial changes. Twenty male patients with a skeletal Class II malrelationship and increased overjet who had been treated at the University of Heidelberg with a modified Andresen-Häupl-type activator were compared with a control group of 15 untreated male subjects of the Belfast Growth Study. The shape changes for each group were visualized on thin-plate splines with one spline comprising all 13 landmarks to show all the craniofacial shape changes, including skeletal and dento-alveolar reactions, and a second spline based on 7 landmarks to visualize only the skeletal changes. In the activator group, the grid deformation of the total spline pointed to a strong activator-induced reduction of the overjet that was caused both by a tipping of the incisors and by a moderation of sagittal discrepancies, particularly a slight advancement of the mandible. In contrast with this, in the control group, only slight localized shape changes could be detected. Both in the 7- and 13-landmark configurations, the shape changes between the groups differed significantly at P < .001. In the present study, the morphometric approach of thin-plate spline analysis turned out to be a useful morphometric supplement to conventional cephalometrics because the complex patterns of shape change could be suggestively visualized.
Chronic Metabolic Acidosis Activates Renal Tubular Sodium Chloride Cotransporter through Angiotension II-dependent WNK4-SPAK Phosphorylation Pathway

PubMed Central

Fang, Yu-Wei; Yang, Sung-Sen; Cheng, Chih-Jen; Tseng, Min-Hua; Hsu, Hui-Min; Lin, Shih-Hua

2016-01-01

The mechanism by which chronic metabolic acidosis (CMA) regulates sodium (Na+)-chloride (Cl−) cotransporter (NCC) in the renal distal convoluted tubules remains unexplored. We examined the role of STE20/SPS1-related proline/alanine-rich kinase (SPAK) and with-no-lysine kinase 4 (WNK4) on expression of NCC in mouse models of CMA. CMA was induced by NH4Cl in wild type mice (WTA mice), SPAK, and WNK4 knockout mice. The quantities of Ncc mRNA, expression of total NCC, phosphorylated (p)-NCC, SPAK and WNK4 in the kidneys as well as NCC inhibition with hydrochlorothiazide and Na+ balance were evaluated. Relative to WT mice, WTA mice had similar levels of Ncc mRNA, but increased expression of total and p-NCC, SPAK, and WNK4 and an exaggerated response to hydrochlorothiazide which could not be observed in SPAK or WNK4 knockout mice with CMA. In WTA mice, increased plasma renin activity, aldosterone and angiotensin II concentrations accompanied by a significantly negative Na+ balance. High Na+ diet abolished the enhanced NCC expression in WTA mice. Furthermore, an angiotensin II type 1 receptor blocker rather than a mineralocorticoid receptor antagonist exerted a marked inhibition on Na+ reabsorption and NCC phosphorylation in WTA mice. CMA increases WNK4-SPAK-dependent NCC phosphorylation and appears to be secondary to previous natriuresis with volume-dependent angiotensin II activation. PMID:26728390
Turbulent transport of He II in active and passive phase separators using slit devices and porous media

NASA Technical Reports Server (NTRS)

Yuan, S. W. K.; Lee, J. M.; Frederking, T. H. K.

1988-01-01

The turbulent transport mode of vapor liquid phase separators (VLPS) for He II has been investigated comparing passive porous plug separators with active phase separators (APS) using slits of variable flow paths within a common frame of reference. It is concluded that the basic transport regimes in both devices are identical. An integrated Gorter-Mellink (1949) equation, found previously to predict VLPS results of porous plugs, is employed to analyze APS data published in the literature. It is found that the Gorter-Mellink flow rate parameter for 9-micron and 14-micron APS slit widths are relatively independent of the slit width, having a rate constant of about 9 + or - 10 percent. This agrees with the early heat flow results for He II entropy transport at zero net mass flow in wide capillaries and slits.
Selective Solid-Phase Extraction of Zinc(II) from Environmental Water Samples Using Ion Imprinted Activated Carbon.

PubMed

Moniri, Elham; Panahi, Homayon Ahmad; Aghdam, Khaledeh; Sharif, Amir Abdollah Mehrdad

2015-01-01

A simple ion imprinted amino-functionalized sorbent was synthesized by coupling activated carbon with iminodiacetic acid, a functional compound for metal chelating, through cyanoric chloride spacer. The resulting sorbent has been characterized using FTIR spectroscopy, elemental analysis, and thermogravimetric analysis and evaluated for the preconcentration and determination of trace Zn(II) in environmental water samples. The optimum pH value for sorption of the metal ion was 6-7.5. The sorption capacity of the functionalized sorbent was 66.6 mg/g. The chelating sorbent can be reused for 10 cycles of sorption-desorption without any significant change in sorption capacity. A recovery of 100% was obtained for the metal ion with 0.5 M nitric acid as the eluent. Compared with nonimprinted polymer particles, the prepared Zn-imprinted sorbent showed high adsorption capacity, significant selectivity, and good site accessibility for Zn(II). Scatchard analysis revealed that the homogeneous binding sites were formed in the polymer. The equilibrium sorption data of Zn(II) by modified resin were analyzed by Langmuir, Freundlich, Temkin, and Redlich-Peterson models. Based on equilibrium adsorption data, the Langmuir, Freundlich, and Temkin constants were determined as 0.139, 12.82, and 2.34, respectively, at 25°C.
Potential of Ranunculus acris L. for biomonitoring trace element contamination of riverbank soils: photosystem II activity and phenotypic responses for two soil series.

PubMed

Marchand, Lilian; Lamy, Pierre; Bert, Valerie; Quintela-Sabaris, Celestino; Mench, Michel

2016-02-01

Foliar ionome, photosystem II activity, and leaf growth parameters of Ranunculus acris L., a potential biomonitor of trace element (TE) contamination and phytoavailability, were assessed using two riverbank soil series. R. acris was cultivated on two potted soil series obtained by mixing a TE (Cd, Cu, Pb, and Zn)-contaminated technosol with either an uncontaminated sandy riverbank soil (A) or a silty clay one slightly contaminated by TE (B). Trace elements concentrations in the soil-pore water and the leaves, leaf dry weight (DW) yield, total leaf area (TLA), specific leaf area (SLA), and photosystem II activity were measured for both soil series after a 50-day growth period. As soil contamination increased, changes in soluble TE concentrations depended on soil texture. Increase in total soil TE did not affect the leaf DW yield, the TLA, the SLA, and the photosystem II activity of R. acris over the 50-day exposure. The foliar ionome did not reflect the total and soluble TE concentrations in both soil series. Foliar ionome of R. acris was only effective to biomonitor total and soluble soil Na concentrations in both soil series and total and soluble soil Mo concentrations in the soil series B.
Synthesis and Properties of Homonuclear, Dimetallic Nickel(II), Copper(II) and Zinc(II) Complexes of p-Xylenediyl and 2-Butynediyl-Bridged Dicyclens

DTIC Science & Technology

1993-05-01

urease which contains two nickel ions in the active site. Catalytic hydrolysis studies are in progress. 20 DISTRIBUTION /AVAILABILITY OF ABSTRACT 21...for hydrolytic metalloenzymes. In contrast, the enzyme urease has becti show’n tU coftifl two nickel(II) ions in the active site," but as yet the

Pyrrolidine dithiocarbamate-zinc(II) and -copper(II) complexes induce apoptosis in tumor cells by inhibiting the proteasomal activity☆

PubMed Central

Milacic, Vesna; Chen, Di; Giovagnini, Lorena; Diez, Alejandro; Fregona, Dolores; Dou, Q. Ping

2013-01-01

Zinc and copper are trace elements essential for proper folding, stabilization and catalytic activity of many metalloenzymes in living organisms. However, disturbed zinc and copper homeostasis is reported in many types of cancer. We have previously demonstrated that copper complexes induced proteasome inhibition and apoptosis in cultured human cancer cells. In the current study we hypothesized that zinc complexes could also inhibit the proteasomal chymotrypsin-like activity responsible for subsequent apoptosis induction. We first showed that zinc(II) chloride was able to inhibit the chymotrypsin-like activity of a purified 20S proteasome with an IC50 value of 13.8 μM, which was less potent than copper(II) chloride (IC50 5.3 μM). We then compared the potencies of a pyrrolidine dithiocarbamate (PyDT)-zinc(II) complex and a PyDT-copper(II) complex to inhibit cellular proteasomal activity, suppress proliferation and induce apoptosis in various human breast and prostate cancer cell lines. Consistently, zinc complex was less potent than copper complex in inhibiting the proteasome and inducing apoptosis. Additionally, zinc and copper complexes appear to use somewhat different mechanisms to kill tumor cells. Zinc complexes were able to activate calpain-, but not caspase-3-dependent pathway, while copper complexes were able to induce activation of both proteases. Furthermore, the potencies of these PyDT-metal complexes depend on the nature of metals and also on the ratio of PyDT to the metal ion within the complex, which probably affects their stability and availability for interacting with and inhibiting the proteasome in tumor cells. PMID:18501397
Removal and recovery of mercury(II) from hazardous wastes using 1-(2-thiazolylazo)-2-naphthol functionalized activated carbon as solid phase extractant.

PubMed

Starvin, A M; Rao, T Prasada

2004-09-10

As a part of removal of toxic heavy metals from hazardous wastes, solid phase extraction (SPE) of mercury(II) at trace and ultra trace levels was studied using 1-(2-thiazolylazo)-2-naphthol (TAN) functionalized activated carbon (AC). The SPE material removes traces of mercury(II) quantitatively in the pH range 6.0 +/- 0.2. Other parameters that influence quantitative recovery of mercury(II), viz. percent concentration of TAN in AC, amount of TAN-AC, preconcentration time and volume of aqueous phase were varied and optimized. The possible means of removal of Hg(II) from other metal ions that are likely to be present in the wastes of the chloroalkali industry is discussed. The potential of TAN-functionalized AC SPE material for decontaminating mercury from the brine sludge and cell house effluent of a chloralkali plant has been evaluated.
Sulfated polysaccharide from the leaves of Artemisia Princeps activates heparin cofactor II independently of the Lys173 and Arg189 residues of heparin cofactor II.

PubMed

Hayashi, T; Hayakawa, Y; Hayashi, T; Sasaki, H; Sakuragawa, N

1997-07-01

A sulfated polysaccharide (AFE-HCD) purified from the leaves of Artemisia princeps Pamp selectively accelerated the rate of thrombin inhibition by heparin cofactor II (HCII). By using plasma derived HCII and bacterial expressed recombinant HCII molecules, the interaction between each HCII molecule and AFE-HCD was analyzed. AFE-HCD accelerated thrombin inhibition by plasma derived HCII or bacterial expressed wild type HCII to the same extent (IC50: 0.056 micrograms/ml for plasma derived HCII and 0.066 micrograms/ml for recombinant HCII under the experimental condition). The recombinant HCII (rHCII) molecule with Lys173-->Leu or Arg189-->His substitution, which is defective in interactions with heparin and dermatan sulfate, respectively, is activated by AFE-HCD to inhibit thrombin in a manner similar to wild type rHCII. These results suggested that activation of HCII was independent of its Lys173 or Arg189 residue. Although AFE-HCD is a selective activator of HCII like dermatan sulfate, the amino acid residue required for the activation of HCII was distinct form that of dermatan sulfate as well as heparin.
Cd(II) and Pb(II) complexes of the polyether ionophorous antibiotic salinomycin

PubMed Central

2011-01-01

Background The natural polyether ionophorous antibiotics are used for the treatment of coccidiosis in poultry and ruminants. They are effective agents against infections caused by Gram-positive microorganisms. On the other hand, it was found that some of these compounds selectively bind lead(II) ions in in vivo experiments, despite so far no Pb(II)-containing compounds of defined composition have been isolated and characterized. To assess the potential of polyether ionophores as possible antidotes in the agriculture, a detailed study on their in vitro complexation with toxic metal ions is required. In the present paper we report for the first time the preparation and the structure elucidation of salinomycin complexes with ions of cadmium(II) and lead(II). Results New metal(II) complexes of the polyether ionophorous antibiotic salinomycin with Cd(II) and Pb(II) ions were prepared and structurally characterized by IR, FAB-MS and NMR techniques. The spectroscopic information and elemental analysis data reveal that sodium salinomycin (SalNa) undergoes a reaction with heavy metal(II) ions to form [Cd(Sal)2(H2O)2] (1) and [Pb(Sal)(NO3)] (2), respectively. Abstraction of sodium ions from the cavity of the antibiotic is occurring during the complexation reaction. Salinomycin coordinates with cadmium(II) ions as a bidentate monoanionic ligand through the deprotonated carboxylic moiety and one of the hydroxyl groups to yield 1. Two salinomycin anions occupy the equatorial plane of the Cd(II) center, while two water molecules take the axial positions of the inner coordination sphere of the metal(II) cation. Complex 2 consists of monoanionic salinomycin acting in polydentate coordination mode in a molar ratio of 1: 1 to the metal ion with one nitrate ion for charge compensation. Conclusion The formation of the salinomycin heavy metal(II) complexes indicates a possible antidote activity of the ligand in case of chronic/acute intoxications likely to occur in the stock farming
Effect of Cu(II), Cd(II) and Zn(II) on Pb(II) biosorption by algae Gelidium-derived materials.

PubMed

Vilar, Vítor J P; Botelho, Cidália M S; Boaventura, Rui A R

2008-06-15

Biosorption of Pb(II), Cu(II), Cd(II) and Zn(II) from binary metal solutions onto the algae Gelidium sesquipedale, an algal industrial waste and a waste-based composite material was investigated at pH 5.3, in a batch system. Binary Pb(II)/Cu(II), Pb(II)/Cd(II) and Pb(II)/Zn(II) solutions have been tested. For the same equilibrium concentrations of both metal ions (1 mmol l(-1)), approximately 66, 85 and 86% of the total uptake capacity of the biosorbents is taken by lead ions in the systems Pb(II)/Cu(II), Pb(II)/Cd(II) and Pb(II)/Zn(II), respectively. Two-metal results were fitted to a discrete and a continuous model, showing the inhibition of the primary metal biosorption by the co-cation. The model parameters suggest that Cd(II) and Zn(II) have the same decreasing effect on the Pb(II) uptake capacity. The uptake of Pb(II) was highly sensitive to the presence of Cu(II). From the discrete model it was possible to obtain the Langmuir affinity constant for Pb(II) biosorption. The presence of the co-cations decreases the apparent affinity of Pb(II). The experimental results were successfully fitted by the continuous model, at different pH values, for each biosorbent. The following sequence for the equilibrium affinity constants was found: Pb>Cu>Cd approximately Zn.
Synthesis, structural characterization and antitumor activity of a Ca(II) coordination polymer based on 4-formyl-1,3-benzenedisulfonate-2-furoic acid hydrazide ligands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tai, Xi-Shi, E-mail: taixs@wfu.edu.cn; Wang, Xin

2017-03-15

A new Ca(II) coordination polymer, ([CaL(H{sub 2}O){sub 4}] · (H{sub 2}O){sub 4}){sub n} (L = 4-formyl-1,3-benzenedisulfonate-2-furoic acid hydrazide) has been prepared by one-pot synthesis method. And it was characterized by elemental analysis, IR and thermal analysis. The result of X-ray single-crystal diffraction analysis shows that the Ca(II) complex molecules form one-dimensional chain structure by the bridging oxygen atoms. The anti-tumor activity of L ligand and the Ca(II) coordination polymer has also been studied.
Free metal ion depletion by "Good's" buffers. III. N-(2-acetamido)iminodiacetic acid, 2:1 complexes with zinc(II), cobalt(II), nickel(II), and copper(II); amide deprotonation by Zn(II), Co(II), and Cu(II).

PubMed

Lance, E A; Rhodes, C W; Nakon, R

1983-09-01

Potentiometric, visible, infrared, electron spin, and nuclear magnetic resonance studies of the complexation of N-(2-acetamido)iminodiacetic acid (H2ADA) by Ca(II), Mg(II), Mn(II), Zn(II), Co(II), Ni(II), and Cu(II) are reported. Ca(II) and Mg(II) were found not to form 2:1 ADA2- to M(II) complexes, while Mn(II), Cu(II), Ni(II), Zn(II), and Co(II) did form 2:1 metal chelates at or below physiological pH values. Co(II) and Zn(II), but not Cu(II), were found to induce stepwise deprotonation of the amide groups to form [M(H-1ADA)4-(2)]. Formation (affinity) constants for the various metal complexes are reported, and the probable structures of the various metal chelates in solution are discussed on the basis of various spectral data.
Dinuclear complexes containing linear M-F-M [M = Mn(II), Fe(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II)] bridges: trends in structures, antiferromagnetic superexchange interactions, and spectroscopic properties.

PubMed

Reger, Daniel L; Pascui, Andrea E; Smith, Mark D; Jezierska, Julia; Ozarowski, Andrew

2012-11-05

The reaction of M(BF(4))(2)·xH(2)O, where M is Fe(II), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II), with the new ditopic ligand m-bis[bis(3,5-dimethyl-1-pyrazolyl)methyl]benzene (L(m)*) leads to the formation of monofluoride-bridged dinuclear metallacycles of the formula [M(2)(μ-F)(μ-L(m)*)(2)](BF(4))(3). The analogous manganese(II) species, [Mn(2)(μ-F)(μ-L(m)*)(2)](ClO(4))(3), was isolated starting with Mn(ClO(4))(2)·6H(2)O using NaBF(4) as the source of the bridging fluoride. In all of these complexes, the geometry around the metal centers is trigonal bipyramidal, and the fluoride bridges are linear. The (1)H, (13)C, and (19)F NMR spectra of the zinc(II) and cadmium(II) compounds and the (113)Cd NMR of the cadmium(II) compound indicate that the metallacycles retain their structure in acetonitrile and acetone solution. The compounds with M = Mn(II), Fe(II), Co(II), Ni(II), and Cu(II) are antiferromagnetically coupled, although the magnitude of the coupling increases dramatically with the metal as one moves to the right across the periodic table: Mn(II) (-6.7 cm(-1)) < Fe(II) (-16.3 cm(-1)) < Co(II) (-24.1 cm(-1)) < Ni(II) (-39.0 cm(-1)) ≪ Cu(II) (-322 cm(-1)). High-field EPR spectra of the copper(II) complexes were interpreted using the coupled-spin Hamiltonian with g(x) = 2.150, g(y) = 2.329, g(z) = 2.010, D = 0.173 cm(-1), and E = 0.089 cm(-1). Interpretation of the EPR spectra of the iron(II) and manganese(II) complexes required the spin Hamiltonian using the noncoupled spin operators of two metal ions. The values g(x) = 2.26, g(y) = 2.29, g(z) = 1.99, J = -16.0 cm(-1), D(1) = -9.89 cm(-1), and D(12) = -0.065 cm(-1) were obtained for the iron(II) complex and g(x) = g(y) = g(z) = 2.00, D(1) = -0.3254 cm(-1), E(1) = -0.0153, J = -6.7 cm(-1), and D(12) = 0.0302 cm(-1) were found for the manganese(II) complex. Density functional theory (DFT) calculations of the exchange integrals and the zero-field splitting on manganese(II) and iron(II) ions were performed
Replacement of Ser108 in Plasmodium falciparum enolase results in weak Mg(II) binding: role of a parasite-specific pentapeptide insert in stabilizing the active conformation of the enzyme.

PubMed

Dutta, Sneha; Mukherjee, Debanjan; Jarori, Gotam K

2015-06-01

A distinct structural feature of Plasmodium falciparum enolase (Pfeno) is the presence of a five amino acid insert -104EWGWS108- that is not found in host enolases. Its conservation among apicomplexan enolases has raised the possibility of its involvement in some important physiological function(s). Deletion of this sequence is known to lower k(cat)/K(m), increase K(a) for Mg(II) and convert dimer into monomers (Vora HK, Shaik FR, Pal-Bhowmick I, Mout R & Jarori GK (2009) Arch Biochem Biophys 485, 128-138). These authors also raised the possibility of the formation of an H-bond between Ser108 and Leu49 that could stabilize the apo-Pfeno in an active closed conformation that has high affinity for Mg(II). Here, we examined the effect of replacement of Ser108 with Gly/Ala/Thr on enzyme activity, Mg(II) binding affinity, conformational states and oligomeric structure and compared it with native recombinant Pfeno. The results obtained support the view that Ser108 is likely to be involved in the formation of certain crucial H-bonds with Leu49. The presence of these interactions can stabilize apo-Pfeno in an active closed conformation similar to that of Mg(II) bound yeast enolase. As predicted, S108G/A-Pfeno variants (where Ser108-Leu49 H-bonds are likely to be disrupted) were found to exist in an open conformation and had low affinity for Mg(II). They also required Mg(II) induced conformational changes to acquire the active closed conformational state essential for catalysis. The possible physiological relevance of apo-Pfeno being in such an active state is discussed. © 2015 FEBS.
Syntheses, structures, and properties of imidazolate-bridged Cu(II)-Cu(II) and Cu(II)-Zn(II) dinuclear complexes of a single macrocyclic ligand with two hydroxyethyl pendants.

PubMed

Li, Dongfeng; Li, Shuan; Yang, Dexi; Yu, Jiuhong; Huang, Jin; Li, Yizhi; Tang, Wenxia

2003-09-22

The imidazolate-bridged homodinuclear Cu(II)-Cu(II) complex, [(CuimCu)L]ClO(4).0.5H(2)O (1), and heterodinuclear Cu(II)-Zn(II) complex, [(CuimZnL(-)(2H))(CuimZnL(-)(H))](ClO(4))(3) (2), of a single macrocyclic ligand with two hydroxyethyl pendants, L (L = 3,6,9,16,19,22-hexaaza-6,19-bis(2-hydroxyethyl)tricyclo[22,2,2,2(11,14)]triaconta-1,11,13,24,27,29-hexaene), have been synthesized as possible models for copper-zinc superoxide dismutase (Cu(2),Zn(2)-SOD). Their crystal structures analyzed by X-ray diffraction methods have shown that the structures of the two complexes are markedly different. Complex 1 crystallizes in the orthorhombic system, containing an imidazolate-bridged dicopper(II) [Cu-im-Cu](3+) core, in which the two copper(II) ions are pentacoordinated by virtue of an N4O environment with a Cu.Cu distance of 5.999(2) A, adopting the geometry of distorted trigonal bipyramid and tetragonal pyramid, respectively. Complex 2 crystallizes in the triclinic system, containing two similar Cu-im-Zn cores in the asymmetric unit, in which both the Cu(II) and Zn(II) ions are pentacoordinated in a distorted trigonal bipyramid geometry, with the Cu.Zn distance of 5.950(1)/5.939(1) A, respectively. Interestingly, the macrocyclic ligand with two arms possesses a chairlike (anti) conformation in complex 1, but a boatlike (syn) conformation in complex 2. Magnetic measurements and ESR spectroscopy of complex 1 have revealed the presence of an antiferromagnetic exchange interaction between the two Cu(II) ions. The ESR spectrum of the Cu(II)-Zn(II) heterodinuclear complex 2 displayed a typical signal for mononuclear trigonal bipyramidal Cu(II) complexes. From pH-dependent ESR and electronic spectroscopic studies, the imidazolate bridges in the two complexes have been found to be stable over broad pH ranges. The cyclic voltammograms of the two complexes have been investigated. Both of the two complexes can catalyze the dismutation of superoxide and show rather high activity.
Mononuclear Pd(II) complex as a new therapeutic agent: Synthesis, characterization, biological activity, spectral and DNA binding approaches

NASA Astrophysics Data System (ADS)

Saeidifar, Maryam; Mirzaei, Hamidreza; Ahmadi Nasab, Navid; Mansouri-Torshizi, Hassan

2017-11-01

The binding ability between a new water-soluble palladium(II) complex [Pd(bpy)(bez-dtc)]Cl (where bpy is 2,2‧-bipyridine and bez-dtc is benzyl dithiocarbamate), as an antitumor agent, and calf thymus DNA was evaluated using various physicochemical methods, such as UV-Vis absorption, Competitive fluorescence studies, viscosity measurement, zeta potential and circular dichroism (CD) spectroscopy. The Pd(II) complex was synthesized and characterized using elemental analysis, molar conductivity measurements, FT-IR, 1H NMR, 13C NMR and electronic spectra studies. The anticancer activity against HeLa cell lines demonstrated lower cytotoxicity than cisplatin. The binding constants and the thermodynamic parameters were determined at different temperatures (300 K, 310 K and 320 K) and shown that the complex can bind to DNA via electrostatic forces. Furthermore, this result was confirmed by the viscosity and zeta potential measurements. The CD spectral results demonstrated that the binding of Pd(II) complex to DNA induced conformational changes in DNA. We hope that these results will provide a basis for further studies and practical clinical use of anticancer drugs.
DNA cleavage, antibacterial, antifungal and anthelmintic studies of Co(II), Ni(II) and Cu(II) complexes of coumarin Schiff bases: synthesis and spectral approach.

PubMed

Patil, Sangamesh A; Prabhakara, Chetan T; Halasangi, Bhimashankar M; Toragalmath, Shivakumar S; Badami, Prema S

2015-02-25

The metal complexes of Co(II), Ni(II) and Cu(II) have been synthesized from 6-formyl-7,8-dihydroxy-4-methylcoumarin with o-toluidine/3-aminobenzotrifluoride. The synthesized Schiff bases and their metal complexes were structurally characterized based on IR, (1)H NMR, (13)C NMR, UV-visible, ESR, magnetic, thermal, fluorescence, mass and ESI-MS studies. The molar conductance values indicate that complexes are non-electrolytic in nature. Elemental analysis reveals ML2·2H2O [M = Co(II), Ni(II) and Cu(II)] stoichiometry, where 'L' stands for a singly deprotonated ligand. The presence of co-ordinated water molecules were confirmed by thermal studies. The spectroscopic studies suggest the octahedral geometry. Redox behavior of the complexes were confirmed by cyclic voltammetry. All the synthesized compounds were screened for their antibacterial (Escherichia coli, Pseudomonas auregenosa, klebsiella, Proteus, Staphylococcus aureus and salmonella) antifungal (Candida, Aspergillus niger and Rhizopus), anthelmintic (Pheretima posthuma) and DNA cleavage (Calf Thymus DNA) activity. Copyright © 2014 Elsevier B.V. All rights reserved.
Enhanced degradation of benzene by percarbonate activated with Fe(II)-glutamate complex.

PubMed

Fu, Xiaori; Gu, Xiaogang; Lu, Shuguang; Miao, Zhouwei; Xu, Minhui; Zhang, Xiang; Danish, Muhammad; Cui, Hang; Farooq, Usman; Qiu, Zhaofu; Sui, Qian

2016-04-01

Effective degradation of benzene was achieved in sodium percarbonate (SPC)/Fe(II)-Glu system. The presence of glutamate (Glu) could enhance the regeneration of Fe(III) to Fe(II), which ensures the benzene degradation efficiency at wider pH range and eliminate the influence of HCO3 (-) in low concentration. Meanwhile, the significant scavenging effects of high HCO3 (-) concentration could also be overcome by increasing the Glu/SPC/Fe(II)/benzene molar ratio. Free radical probe compound tests, free radical scavenger tests, and electron paramagnetic resonance (EPR) analysis were conducted to explore the reaction mechanism for benzene degradation, in which hydroxyl radical (HO•) and superoxide anion radical (O2 (•-)) were confirmed as the predominant species responsible for benzene degradation. In addition, the results obtained in actual groundwater test strongly indicated that SPC/Fe(II)-Glu system is applicable for the remediation of benzene-contaminated groundwater in practice.
[Heparin-induced thrombocytopenia type II (HIT II) : A medical-economic view].

PubMed

Riedel, R; Schmieder, A; Koster, A; Kim, S; Baumgarten, G; Schewe, J C

2017-05-01

In the context of inpatient and increasingly ambulatory thrombosis prophylaxis, heparins have been recognised as standard therapy for decades. In addition to the therapeutic benefit, therapy with heparins also entails the risk of undesirable side effects, such as bleeding and thrombocytopenia. Heparin-induced thrombocytopenia (HIT II) is deemed a serious side effect. In the following work, HIT II is subjected to a medico-economic consideration (treatment, pharmaceuticals, subsequent costs due to possible complications) and, with regard to a possible HIT II prophylaxis, aspects of increasingly respected patient safety are also considered. In the context of a literature search the active ingredients argatroban and danaparoid, which are approved for HIT II treatment, were evaluated. HIT II - especially in combination with thromboembolic complications - represents a medical-economic burden for the hospital. Although this is only an orientation guide, it shows that HIT II syndrome is not adequately cost-covered by the G‑DRG system. An early thrombosis prophylaxis with argatroban/danaparoid for HIT II risk patients should therefore be taken into account for medical-related as well as patient safety-relevant aspects. According to experience, the pharmaceutical supply for these medically needed products (anticoagulants) should be ensured for reasons of patient safety. The risk of an immunological response to heparin therapy is known. Within the context of increased patient safety, thrombosis prophylaxis should be issued with a risk-adjusted prophylaxis.
Antitumour activity mediated by CD4+ cytotoxic T lymphocytes against MHC class II-negative mouse hepatocellular carcinoma induced by dendritic cell vaccine and interleukin-12.

PubMed

Homma, Sadamu; Komita, Hideo; Sagawa, Yukiko; Ohno, Tsuneya; Toda, Gotaro

2005-08-01

When BALA/c mice with BNL hepatocellular carcinoma (HCC) were treated with dendritic cells fused with BNL cells (DC/BNL) and recombinant murine interleukin (IL)-12, tumour development was significantly suppressed, whereas treatment with either DC/BNL or IL-12 alone did not show a tumour-suppressive effect. Antitumour activity induced by DC/BNL + IL-12 was abrogated by depletion of CD4+ T cells, but not by depletion of CD8+ T cells or natural killer cells. Splenic CD4+ T cells and CD8+ T cells from DC/BNL-treated mice showed cytotoxic activity against BNL cells after 3 days of incubation with DC/BNL, although BNL cells do not express major histocompatibility complex (MHC) class II molecules even after treatment with interferon (INF)-gamma. Furthermore, CD4+ T cells killed syngeneic-irrelevant CT26 cells and even allogeneic Hepa1-6 cells. This cytotoxicity was blocked by concanamycin A, but not by an anti-Fas ligand (FasL) monoclonal antibody, indicating that cytotoxic activity was mediated by perforin. Immunofluorescence microscopy demonstrated that abundant CD4+ T cells and MHC class II-positive macrophages, but not CD8(+) T cells, had infiltrated tumour tissue in mice treated with DC/BNL + IL-12. Flow cytometric analysis of tumour-infiltrating cells in mice treated with DC/BNL + IL-12 showed increases in CD4+ T cells and MHC class II+ CD11b+ cells but not in CD8+ T cells or MHC class I+ CD11b+ cells. Our results suggest that, in BNL-bearing mice treated with DC/BNL + IL-12, tumour macrophages activated by INF-gamma produced by IL-12-stimulated T cells might present BNL tumour antigens and activate DC/BNL-primed CD4+ cytotoxic T lymphocytes (CTLs) in a MHC class II-dependent manner, leading to perforin-mediated bystander killing of neighbouring MHC class II-negative tumour cells.
Antitumour activity mediated by CD4+ cytotoxic T lymphocytes against MHC class II-negative mouse hepatocellular carcinoma induced by dendritic cell vaccine and interleukin-12

PubMed Central

Homma, Sadamu; Komita, Hideo; Sagawa, Yukiko; Ohno, Tsuneya; Toda, Gotaro

2005-01-01

When BALA/c mice with BNL hepatocellular carcinoma (HCC) were treated with dendritic cells fused with BNL cells (DC/BNL) and recombinant murine interleukin (IL)-12, tumour development was significantly suppressed, whereas treatment with either DC/BNL or IL-12 alone did not show a tumour-suppressive effect. Antitumour activity induced by DC/BNL + IL-12 was abrogated by depletion of CD4+ T cells, but not by depletion of CD8+ T cells or natural killer cells. Splenic CD4+ T cells and CD8+ T cells from DC/BNL-treated mice showed cytotoxic activity against BNL cells after 3 days of incubation with DC/BNL, although BNL cells do not express major histocompatibility complex (MHC) class II molecules even after treatment with interferon (INF)-γ. Furthermore, CD4+ T cells killed syngeneic-irrelevant CT26 cells and even allogeneic Hepa1-6 cells. This cytotoxicity was blocked by concanamycin A, but not by an anti-Fas ligand (FasL) monoclonal antibody, indicating that cytotoxic activity was mediated by perforin. Immunofluorescence microscopy demonstrated that abundant CD4+ T cells and MHC class II-positive macrophages, but not CD8+ T cells, had infiltrated tumour tissue in mice treated with DC/BNL + IL-12. Flow cytometric analysis of tumour-infiltrating cells in mice treated with DC/BNL + IL-12 showed increases in CD4+ T cells and MHC class II+ CD11b+ cells but not in CD8+ T cells or MHC class I+ CD11b+ cells. Our results suggest that, in BNL-bearing mice treated with DC/BNL + IL-12, tumour macrophages activated by INF-γ produced by IL-12-stimulated T cells might present BNL tumour antigens and activate DC/BNL-primed CD4+ cytotoxic T lymphocytes (CTLs) in a MHC class II-dependent manner, leading to perforin-mediated bystander killing of neighbouring MHC class II-negative tumour cells. PMID:16011514
Stachybotrys chartarum alters surfactant-related phospholipid synthesis and CTP:cholinephosphate cytidylyltransferase activity in isolated fetal rat type II cells.

PubMed

Hastings, C; Rand, T; Bergen, H T; Thliveris, J A; Shaw, A R; Lombaert, G A; Mantsch, H H; Giles, B L; Dakshinamurti, S; Scott, J E

2005-03-01

Stachybotry chartarum, a fungal contaminant of water-damaged buildings commonly grows on damp cellulose-containing materials. It produces a complex array of mycotoxins. Their mechanisms of action on the pulmonary system are not entirely clear. Previous studies suggest spore products may depress formation of disaturated phosphatidylcholine (DSPC), the major surface-active component of pulmonary surfactant (PS). If S. chartarum can indeed affect formation of this phospholipid, then mold exposure may be a significant issue for pulmonary function in both mature lung and developing fetal lung. To address this possibility, fetal rat type II cells, the principal source of DSPC, were used to assess effects of S. chartarum extract on formation of DSPC. Isolated fetal rat lung type II cells prelabeled with 3H-choline and incubated with spore extract showed decreased incorporation of 3H-choline into DSPC. The activity of CTP:cholinephosphate cytidylyltransferase (CPCT), the rate-limiting enzyme in phosphatidylcholine synthesis was reduced by approximately 50% by a 1:10 dilution of spore extract. Two different S. chartarum extracts (isolates from S. chartarum (Cleveland) and S. chartarum (Hawaiian)) were used to compare activity of CPCT in the presence of phosphatidylglycerol (PG), a known activator. PG produced an approximate two-fold increase in CPCT activity. The spore isolate from Hawaii did not alter enzyme activity. S. chartarum (Cleveland) eliminated the PG-induced activation of CPCT. These results support previous observations that mold products alter PS metabolism and may pose a risk in developing lung, inhibiting surfactant synthesis. Different isolates of the same species of fungus are not equivalent in terms of potential exposure risks.
Binding Selectivity of Methanobactin from Methylosinus trichosporium OB3b for Copper(I), Silver(I), Zinc(II), Nickel(II), Cobalt(II), Manganese(II), Lead(II), and Iron(II).

PubMed

McCabe, Jacob W; Vangala, Rajpal; Angel, Laurence A

2017-12-01

Methanobactin (Mb) from Methylosinus trichosporium OB3b is a member of a class of metal binding peptides identified in methanotrophic bacteria. Mb will selectively bind and reduce Cu(II) to Cu(I), and is thought to mediate the acquisition of the copper cofactor for the enzyme methane monooxygenase. These copper chelating properties of Mb make it potentially useful as a chelating agent for treatment of diseases where copper plays a role including Wilson's disease, cancers, and neurodegenerative diseases. Utilizing traveling wave ion mobility-mass spectrometry (TWIMS), the competition for the Mb copper binding site from Ag(I), Pb(II), Co(II), Fe(II), Mn(II), Ni(II), and Zn(II) has been determined by a series of metal ion titrations, pH titrations, and metal ion displacement titrations. The TWIMS analyses allowed for the explicit identification and quantification of all the individual Mb species present during the titrations and measured their collision cross-sections and collision-induced dissociation patterns. The results showed Ag(I) and Ni(II) could irreversibly bind to Mb and not be effectively displaced by Cu(I), whereas Ag(I) could also partially displace Cu(I) from the Mb complex. At pH ≈ 6.5, the Mb binding selectivity follows the order Ag(I)≈Cu(I)>Ni(II)≈Zn(II)>Co(II)>Mn(II)≈Pb(II)>Fe(II), and at pH 7.5 to 10.4 the order is Ag(I)>Cu(I)>Ni(II)>Co(II)>Zn(II)>Mn(II)≈Pb(II)>Fe(II). Breakdown curves of the disulfide reduced Cu(I) and Ag(I) complexes showed a correlation existed between their relative stability and their compact folded structure indicated by their CCS. Fluorescence spectroscopy, which allowed the determination of the binding constant, compared well with the TWIMS analyses, with the exception of the Ni(II) complex. Graphical abstract ᅟ.
Tripeptidyl-peptidase II: a multi-purpose peptidase.

PubMed

Tomkinson, Birgitta; Lindås, Ann-Christin

2005-10-01

Tripeptidyl-peptidase II is a high-molecular weight peptidase with a widespread distribution in eukaryotic cells. The enzyme sequentially removes tripeptides from a free N-terminus of longer peptides and also displays a low endopeptidase activity. A role for tripeptidyl-peptidase II in the formation of peptides for antigen presentation has recently become evident, and the enzyme also appears to be important for the degradation of some specific substrates, e.g. the neuropeptide cholecystokinin. However, it is likely that the main biological function of tripeptidyl-peptidase II is to participate in a general intracellular protein turnover. This peptidase may act on oligopeptides generated by the proteasome, or other endopeptidases, and the tripeptides formed would subsequently be good substrates for other exopeptidases. The fact that tripeptidyl-peptidase II activity is increased in sepsis-induced muscle wasting, a situation of enhanced protein turnover, corroborates this biological role.
Salivary alkaline phosphatase and calcium in caries-active type II diabetes mellitus patients: An in vivo study

PubMed Central

Hegde, Mithra N.; Tahiliani, Divya; Shetty, Shilpa; Devadiga, Darshana

2014-01-01

Background: Diabetes Mellitus is a metabolic syndrome, affecting the oral health in various ways with dental caries being one of the most common problems encountered. Saliva is one of the most abundant secretions in the human body with a variety of natural protective and defence molecules bathing the oral cavity maintaining equilibrium. Its collection is easy and non-invasive. Aims: To compare and evaluate salivary alkaline phosphatase levels and calcium ion levels between caries active type II diabetes mellitus patients and non-diabetics. Materials and Methods: This study was carried out on caries-active age and gender matched 60 non-diabetic and 60 patients with known Type II diabetes mellitus subjects of age group 25-50 years with DMFT index >10. Saliva sample was collected to analyse for alkaline phosphatase enzyme and concentration of calcium ions using Agappe kits. Statistical Analysis: Student ‘t’ test was used to correlate the salivary electrolyte concentration in non- diabetic and diabetic patients with dental caries. A ‘P’ value of 0.05 or less was considered significant. Results are presented as mean ± standard deviation (X ± SD). Results: The alkaline phosphatase (ALP) activity in saliva was higher in diabetic patients when compared to that of non-diabetic patients with salivary calcium ions were significantly higher in non-diabetic individuals. Conclusion: Diabetes Mellitus patients are more prone to dental caries, hence require intervention to improve the quality of saliva. PMID:25395756

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