Absolute Thellier paleointensities from Ponta Grossa dikes (southern Brazil) and the early Cretaceous geomagnetic field strength

We report a detailed rock magnetic and Thellier paleointensity study from similar to 130.5 Ma Ponta Grossa Dike Swarms in Southern Brazil. Twenty-nine samples from seven cooling units were pre-selected for paleointensity experiments based on their low viscosity index, stable remanent magnetization and close to reversible continuous thermomagnetic curves. 19 samples characterized by negative pTRM tests, Arai concave- up curves or positive pTRM tests with NRM loss uncorrelated with TRM acquisition were rejected. High quality reliable paleointensity determinations are determined from detailed evaluation criteria, with 10 samples belonging to three dikes passing the tests. The site-mean paleointensity values obtained in this study range from 25.6 +/- 4.3 to 11.3 +/- 2.1 mu T and the corresponding VDM`s range from 5.7 +/- 0.9 to 2.5 +/- 0.5 (10(22) Am(2)). These data yield a VDM mean value of 4.1 +/- 1.6 x 10(22) Am(2). Significant variability of Earth`s magnetic field strength is observed for Ponta Grossa Dikes with the mean value being significantly lower as compared to the mean VDM obtained from the nearby Parana Magmatic Province. The paleointensities for the Ponta Grossa Dikes are in agreement with absolute paleointensities retrieved from the submarine basaltic glasses from 130 to 120 Ma. It seems that a relatively low field prevailed just before the Cretaceous Normal Superchron.

Dipeptidyl peptidase IV inhibition downregulates Na(+)-H(+) exchanger NHE3 in rat renal proximal tubule

In the microvillar microdomain of the kidney brush border, sodium hydrogen exchanger type 3 (NHE3) exists in physical complexes with the serine protease dipeptidyl peptidase IV (DPPIV). The purpose of this study was to explore the functional relationship between NHE3 and DPPIV in the intact proximal tubule in vivo. To this end, male Wistar rats were treated with an injection of the reversible DPPIV inhibitor Lys [Z(NO(2))]-pyrrolidide (I40; 60 mg center dot kg(-1)center dot day(-1) ip) for 7 days. Rats injected with equal amounts of the noninhibitory compound Lys[ Z(NO(2))]-OH served as controls. Na(+) -H(+) exchange activity in isolated microvillar membrane vesicles was 45 +/- 5% decreased in rats treated with I40. Membrane fractionation studies using isopycnic centrifugation revealed that I40 provoked redistribution of NHE3 along with a small fraction of DPPIV from the apical enriched microvillar membranes to the intermicrovillar microdomain of the brush border. I40 significantly increased urine output ( 67 +/- 9%; P < 0.01), fractional sodium excretion ( 63 +/- 7%; P < 0.01), as well as lithium clearance ( 81 +/- 9%; P < 0.01), an index of end-proximal tubule delivery. Although not significant, a tendency toward decreased blood pressure and plasma pH/HCO(3)(-) was noted in I40-treated rats. These findings indicate that inhibition of DPPIV catalytic activity is associated with inhibition of NHE3-mediated NaHCO(3) reabsorption in rat renal proximal tubule. Inhibition of apical Na(+) -H(+) exchange is due to reduced abundance of NHE3 protein in the microvillar microdomain of the kidney brush border. Moreover, this study demonstrates a physiologically significant interaction between NHE3 and DPPIV in the intact proximal tubule in vivo.

Alboserpin, a Factor Xa Inhibitor from the Mosquito Vector of Yellow Fever, Binds Heparin and Membrane Phospholipids and Exhibits Antithrombotic Activity

The molecular mechanism of factor Xa (FXa) inhibition by Alboserpin, the major salivary gland anticoagulant from the mosquito and yellow fever vector Aedes albopictus, has been characterized. cDNA of Alboserpin predicts a 45-kDa protein that belongs to the serpin family of protease inhibitors. Recombinant Alboserpin displays stoichiometric, competitive, reversible and tight binding to FXa (picomolar range). Binding is highly specific and is not detectable for FX, catalytic site-blocked FXa, thrombin, and 12 other enzymes. Alboserpin displays high affinity binding to heparin (K(D) similar to 20 nM), but no change in FXa inhibition was observed in the presence of the cofactor, implying that bridging mechanisms did not take place. Notably, Alboserpin was also found to interact with phosphatidylcholine and phosphatidylethanolamine but not with phosphatidylserine. Further, annexin V (in the absence of Ca(2+)) or heparin outcompetes Alboserpin for binding to phospholipid vesicles, suggesting a common binding site. Consistent with its activity, Alboserpin blocks prothrombinase activity and increases both prothrombin time and activated partial thromboplastin time in vitro or ex vivo. Furthermore, Alboserpin prevents thrombus formation provoked by ferric chloride injury of the carotid artery and increases bleeding in a dose-dependent manner. Alboserpin emerges as an atypical serpin that targets FXa and displays unique phospholipid specificity. It conceivably uses heparin and phosphatidylcholine/phosphatidylethanolamine as anchors to increase protein localization and effective concentration at sites of injury, cell activation, or inflammation.

Intracellular peptides as natural regulators of cell signaling

Protein degradation by the ubiquitin proteasome system releases large amounts of oligopeptides within cells. To investigate possible functions for these intracellularly generated oligopeptides, we fused them to a cationic transactivator peptide sequence using reversible disulfide bonds, introduced them into cells, and analyzed their effect on G protein-coupled receptor (GPCR) signal transduction. A mixture containing four of these peptides (20-80 mu M) significantly inhibited the increase in the extracellular acidification response triggered by angiotensin II (ang II) in CHO-S cells transfected with the ang II type 1 receptor (AT1R-CHO-S). Subsequently, either alone or in a mixture, these peptides increased luciferase gene transcription in AT1R-CHO-S cells stimulated with ang II and in HEK293 cells treated with isoproterenol. These peptides without transactivator failed to affect GPCR cellular responses. All four functional peptides were shown in vitro to competitively inhibit the degradation of a synthetic substrate by thimet oligopeptidase. Overexpression of thimet oligopeptidase in both CHO-S and HEK293 cells was sufficient to reduce luciferase activation triggered by a specific GPCR agonist. Moreover, using individual peptides as baits in affinity columns, several proteins involved in GPCR signaling were identified, including alpha-adaptin A and dynamin 1. These results suggest that before their complete degradation, intracellular peptides similar to those generated by proteasomes can actively affect cell signaling, probably representing additional bioactive molecules within cells.

Eugenol modifies the excitability of rat sciatic nerve and superior cervical ganglion neurons

Eugenol is a phenylpropene obtained from the essential oils of plants such as clove and basil which has ample use in dentistry. Eugenol possesses analgesic effects that may be related to the inhibition of voltage-dependent Na(+) channels and/or to the activation of TRPV1 receptors or both. In the present study, electrophysiological parameters were taken from the compound action potentials of the isolated rat sciatic nerve and from neurons of the superior cervical ganglion (SCG) impaled with sharp microelectrodes under current-clamp conditions. In the isolated rat sciatic nerve, eugenol inhibited the compound action potential in a concentration-dependent manner. Action potentials recorded from SCG neurons were inhibited by eugenol with an IC(50) of 0.31 mM. At high concentrations (2 mM), during brief applications. eugenol caused significant action potential blockade while it did not interfere with the resting membrane potential or the membrane input resistance. Surprisingly, however, at low eugenol concentrations (0.6 mM), during long time applications, a reversible reduction (by about 50%) in the input membrane resistance was observed, suggesting the possible involvement of a secondary delayed effect of eugenol to reduce neuronal excitability. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Loops, Chains, Sheets, and Networks from Variable Coordination of Cu(hfac)(2) with a Flexibly Hinged Aminoxyl Radical Ligand

One pair of reactants, Cu(hfac)(2) = M and the hinge-flexible radical ligand 5-(3-N-tert-butyl-N-aminoxylphenyl)pyrimidine (3PPN = L), yields a diverse set of five coordination complexes: a cyclic loop M(2)L(1) dimer; a 1:1 cocrystal between an M(2)L(2) loop and an ML(2) fragment; a ID chain of M(2)L(2) loops linked by M; two 2D M(3)L(2) networks of (M-L)(n) chains crosslinked by M with different repeat length pitches; a 3D M(3)L(2) network of M(2)L(2) loops cross-linking (M-L)(n)-type chains with connectivity different from those in the 2D networks. Most of the higher dimensional complexes exhibit reversible, temperature-dependent spin-state conversion of high-temperature paramagnetic states to lower magnetic moment states having antiferromagnetic exchange within Cu-ON bonds upon cooling, with accompanying bond contraction. The 3D complex also exhibited antiferromagnetic exchange between Cu(II) ions linked in chains through pyrimidine rings.

First order reversal curve analysis of nanocrystalline Pd(80)Co(20) alloy films

Films of isotropic nanocrystalline Pd(80)Co(20) alloys were obtained by electrodeposition onto brass substrate in plating baths maintained at different pH values. Increasing the pH of the plating bath led to an increase in mean grain size without inducing significant changes in the composition of the alloy. The magnetocrystalline anisotropy constant was estimated and the value was of the same order of magnitude as that reported for samples with perpendicular magnetic anisotropy. First order reversal curve (FORC) analysis revealed the presence of an important component of reversible magnetization. Also, FORC diagrams obtained at different sweep rate of the applied magnetic field, revealed that this reversible component is strongly affected by kinetic effect. The slight bias observed in the irreversible part of the FORC distribution suggested the dominance of magnetizing intergrain exchange coupling over demagnetizing dipolar interactions and microstructural disorder. (c) 2009 Elsevier B.V. All rights reserved.

Optical VOCs detection using poly(3-alkylthiophenes) with different side-chain lengths

The use of conjugated polymers in the gas and volatile organic compounds (VOCs) detections represents an advance in the development of the electronic noses. Polythiophenes show good thermal and environmental stability, are easily synthesized and they have been studied as gas and VOCs sensors using different principles or transduction techniques. Among these techniques, optical sensing has been attracted attention, mainly due to its versatility. However, conjugated polymer-based optical sensors are still less studied. This paper describes the use of two poly(3-alkylthiophenes) for VOCs optical detection. The sensing measurements were carried out using visible spectroscopy. Both polymers showed good sensitivity to the VOCs, showing fast and reversible responses with some hysteresis, and were unable to detect hydroxylated samples. Furthermore, it was demonstrated that the thickness of polymer films influences the intensity of the optical response. Although there is similarity in the superficial composition of the polymers films, demonstrated by their surface energies, they showed significant differences in their optical properties upon exposure to the VOCs. (c) 2009 Elsevier B.V. All rights reserved.

Synthesis of azopolymers with controlled structure and photoinduced birefringence in their LB films

The molecular architecture of azopolymers may be controlled via chemical synthesis and with selection of a suitable film-forming method, which is important for improving their properties for practical uses. Here we address the main challenge of combining the photoinduced birefringence features of azopolymers with the higher thermal and mechanical stabilities of poly(methyl methacrylate) (PMMA) using Atom Transfer Radical Polymerization (ATRP) to synthesize diblock- and triblock-copolymers of an azomonomer and the monomer methyl methacrylate. Langmuir-Blodgett (LB) films made with the copolymers mixed with cadmium stearate displayed essentially the same optically induced birefringence characteristics, in terms of maximum and residual birefringence and time for writing, as the mixed LB films with the homopolymer poly[4-(N-ethyl-N-(2-methacryloxyethyl))amino-2`-chloro-4`-nitroazobenzene] (HPDR13), also synthesized via ATRP. In fact, the controlled architecture of HPDR13 chains led to Langmuir films that could be more closely packed and reach higher collapse pressures than the corresponding films obtained with HPDR13-conv synthesized via conventional radicalar polymerization. This allowed LB films to be fabricated from neat HPDR13, which was not possible with HPDR13-conv. The enhanced organization in the LB films produced with controlled azopolymer chains, however, led to a smaller free volume available for isomerization of the azochromophores, thus yielding a lower photoinduced birefringence than in the HPDR13-conv films. The combination of ATRP synthesis and LB technology is then promising to obtain optical storage in films with improved thermal and mechanical processabilities, though a further degree of control must be sought to exploit film organization while maintaining the necessary free volume in the films. (C) 2008 Elsevier Ltd. All rights reserved.

Thermodynamic characterization of the palm tree Roystonea regia peroxidase stability

The structural stability of a peroxidase, a dimeric protein from royal palm tree (Roystonea regia) leaves, has been characterized by high-sensitivity differential scanning calorimetry, circular dichroism, steady-state tryptophan fluorescence and analytical ultracentifugation under different solvent conditions. It is shown that the thermal and chemical (using guanidine hydrochloride (Gdn-HCl)) folding/unfolding of royal palm tree peroxidase (RPTP) at pH 7 is a reversible process involving a highly cooperative transition between the folded dimer and unfolded monomers, with a free stabilization energy of about 23 kcal per mol of monomer at 25 degrees C. The structural stability of RPTP is pH-dependent. At pH 3, where ion pairs have disappeared due to protonation, the thermally induced denaturation of RPTP is irreversible and strongly dependent upon the scan rate, suggesting that this process is under kinetic control. Moreover, thermally induced transitions at this pH value are dependent on the protein concentration, allowing it to be concluded that in solution RPTP behaves as dimer, which undergoes thermal denaturation coupled with dissociation. Analysis of the kinetic parameters of RPTP denaturation at pH 3 was accomplished on the basis of the simple kinetic scheme N ->(k) D, where k is a first-order kinetic constant that changes with temperature, as given by the Arrhenius equation; N is the native state, and D is the denatured state, and thermodynamic information was obtained by extrapolation of the kinetic transition parameters to an infinite heating rate. Obtained in this way, the value of RPTP stability at 25 degrees C is ca. 8 kcal per mole of monomer lower than at pH 7. In all probability, this quantity reflects the contribution of ion pair interactions to the structural stability of RPTP. From a comparison of the stability of RPTP with other plant peroxidases it is proposed that one of the main factors responsible for the unusually high stability of RPTP which enhances its potential use for biotechnological purposes, is its dimerization. (c) 2008 Elsevier Masson SAS. All rights reserved.

Study of the carbon dioxide chemical fixation-activation by guanidines

Fixation of CO(2) is one of the most important priorities of the scientific community dedicated to reduce global warming. In this work, we propose new methods for the fixation of CO2 using the guanidine bases tetramethylguanidine (TMG) and 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]-pyrimidine (TBD). In order to understand the reactions occurring during the CO(2) fixation and release processes, we employed several experimental methods, including solution and solid-state NMR, FTIR, and coupled TGA-FTIR. Quantum mechanical NMR calculations were also carried out. Based on the results obtained, we concluded that CO(2) fixation with both TMG and TBD guanidines is a kinetically reversible process, and the corresponding fixation products have proved to be useful as transcarboxylating compounds. Afterward, CO(2) thermal releasing from this fixation product with TBD was found to be an interesting process for CO(2) capture and isolation purposes. (C) 2008 Elsevier Ltd. All rights reserved.

Acridone alkaloids as potent inhibitors of cathepsin V

Cathepsin V is a lysosomal cysteine peptidase highly expressed in thymus, testis and corneal epithelium. Eleven acridone alkaloids were isolated from Swinglea glutinosa (Bl.) Merr. (Rutaceae), with eight of them being identified as potent and reversible inhibitors of cathepsin V (IC(50) values ranging from 1.2 to 3.9 mu M). Detailed mechanistic characterization of the effects of these compounds on the cathepsin V-catalyzed reaction showed clear competitive inhibition with respect to substrate, with dissociation constants (K(i)) in the low micromolar range (2, K(i) = 1.2 mu M; 6, K(i) = 1.0 mu M; 7, K(i) = 0.2 mu M; and 11, K(i) = 1.7 mu M). Molecular modeling studies provided important insight into the structural basis for binding affinity and enzyme inhibition. Experimental and computational approaches, including biological evaluation, mode of action assessment and modeling studies were successfully employed in the discovery of a small series of acridone alkaloid derivatives as competitive inhibitors of catV. The most potent inhibitor (7) has a K(i) value of 200 nM. (C) 2011 Elsevier Ltd. All rights reserved.

Inhibition of Mycobacterium tuberculosis tyrosine phosphatase PtpA by synthetic chalcones: Kinetics, molecular modeling, toxicity and effect on growth

Tuberculosis (TB) is a major cause of morbidity and mortality throughout the world, and it is estimated that one-third of the world`s population is infected with Mycobacterium tuberculosis. Among a series of tested compounds, we have recently identified five synthetic chalcones which inhibit the activity of M. tuberculosis protein tyrosine phosphatase A (PtpA), an enzyme associated with M. tuberculosis infectivity. Kinetic studies demonstrated that these compounds are reversible competitive inhibitors. In this work we also carried out the analysis of the molecular recognition of these inhibitors on their macromolecular target, PtpA, through molecular modeling. We observed that the predominant determinants responsible for the inhibitory activity of the chalcones are the positions of the two methoxyl groups at the A-ring, that establish hydrogen bonds with the amino acid residues Arg17, His49, and Thr12 in the active site of PtpA, and the substitution of the phenyl ring for a 2-naphthyl group as B-ring, that undergoes p stacking hydrophobic interaction with the Trp48 residue from PtpA. Interestingly, reduction of mycobacterial survival in human macrophages upon inhibitor treatment suggests their potential use as novel therapeutics. The biological activity, synthetic versatility, and low cost are clear advantages of this new class of potential tuberculostatic agents. (C) 2010 Elsevier Ltd. All rights reserved.

Density-Profile Processes Describing Biological Signaling Networks: Almost Sure Convergence to Deterministic Trajectories

We introduce jump processes in R(k), called density-profile processes, to model biological signaling networks. Our modeling setup describes the macroscopic evolution of a finite-size spin-flip model with k types of spins with arbitrary number of internal states interacting through a non-reversible stochastic dynamics. We are mostly interested on the multi-dimensional empirical-magnetization vector in the thermodynamic limit, and prove that, within arbitrary finite time-intervals, its path converges almost surely to a deterministic trajectory determined by a first-order (non-linear) differential equation with explicit bounds on the distance between the stochastic and deterministic trajectories. As parameters of the spin-flip dynamics change, the associated dynamical system may go through bifurcations, associated to phase transitions in the statistical mechanical setting. We present a simple example of spin-flip stochastic model, associated to a synthetic biology model known as repressilator, which leads to a dynamical system with Hopf and pitchfork bifurcations. Depending on the parameter values, the magnetization random path can either converge to a unique stable fixed point, converge to one of a pair of stable fixed points, or asymptotically evolve close to a deterministic orbit in Rk. We also discuss a simple signaling pathway related to cancer research, called p53 module.

Billiards in a General Domain with Random Reflections

We study stochastic billiards on general tables: a particle moves according to its constant velocity inside some domain D R(d) until it hits the boundary and bounces randomly inside, according to some reflection law. We assume that the boundary of the domain is locally Lipschitz and almost everywhere continuously differentiable. The angle of the outgoing velocity with the inner normal vector has a specified, absolutely continuous density. We construct the discrete time and the continuous time processes recording the sequence of hitting points on the boundary and the pair location/velocity. We mainly focus on the case of bounded domains. Then, we prove exponential ergodicity of these two Markov processes, we study their invariant distribution and their normal (Gaussian) fluctuations. Of particular interest is the case of the cosine reflection law: the stationary distributions for the two processes are uniform in this case, the discrete time chain is reversible though the continuous time process is quasi-reversible. Also in this case, we give a natural construction of a chord ""picked at random"" in D, and we study the angle of intersection of the process with a (d - 1) -dimensional manifold contained in D.