Inhibition of C6 rat glioma proliferation by [Ru(2)Cl(Ibp)(4)] depends on changes in p21, p27, Bax/Bcl2 ratio and mitochondrial membrane potential

The ruthenium compound [Ru(2)Cl(Ibp)(4)] (or RuIbp) has been reported to cause significantly greater inhibition of C6 glioma cell proliferation than the parent HIbp. The present study determined the effects of 0-72 h exposure to RuIbp upon C6 cell cycle distribution, mitochondrial membrane potential, reactive species generation and mRNA and protein expression of E2F1, cyclin D1, c-myc, pRb, p21, p27, p53, Ku70, Ku80, Bax, Bcl2, cyclooxygenase 1 and 2 (COX1 and COX2). The most significant changes in mRNA and protein expression were seen for the cyclin-dependent kinase inhibitors p21 and p27 which were both increased (p<0.05). The marked decrease in mitochondrial membrane potential (p<0.01) and modest increase in apoptosis was accompanied by a decrease in anti-apoptotic Bcl2 expression and an increase in pro-apoptotic Bax expression (p<0.05). Interestingly, COX1 expression was increased in response to a significant loss of prostaglandin E(2) production (p<0.001), most likely due to the intracellular action of Ibp. Future studies will investigate the efficacy of this novel ruthenium-ibuprofen complex in human glioma cell lines in vitro and both rat and human glioma cells growing under orthotopic conditions in vivo. (C) 2010 Elsevier Inc. All rights reserved.

The combined effect of copper and low pH on antioxidant defenses and biochemical parameters in neotropical fish pacu, Piaractus mesopotamicus (Holmberg, 1887)

Copper sulfate is widely used in aquaculture. Exposure to this compound can be harmful to fish, resulting in oxidative metabolism alterations and gill tissue damage. Pacu, Piaractus mesopotamicus, (wt = 43.4 +/- A 3.35 g) were distributed in experimental tanks (n = 10; 180 l) and exposed for 48 h to control (without copper addition), 0.4Cu (0.4 mg l(-1)), 0CupH (without copper addition, pH = 5.0) and 0.4CupH (0.4 mg l(-1), pH = 5.0). In liver and red muscle, the superoxide dismutase (SOD) was responsive to the increases in the aquatic copper. The plasmatic intermediary metabolites and hematological variables in the fish of group 0.4Cu were similar to those of the control group. Conversely, the exposure to 0.4CupH caused an increase in the plasmatic lactate, number of red blood cells (RBC) and hemoglobin (Hb). Plasmatic copper concentration [Cu(p)] increased in group 0.4Cu and 0.4CupH, which is higher in group 0.4CupH, suggests an effect of water pH on the absorbed copper. Exposure to 0.4Cu and 0.4CupH resulted in a reduction in the Na(+)/K(+)-ATPase activity and an increase in metallothionein (MT) in the gills. Exposure to 0CupH caused a decrease in glucose and pyruvate concentrations and an increase in RBC, Hb, and the branchial Na(+)/K(+)-ATPase activity. These responses suggest that the fish triggered mechanisms to revert the blood acidosis, save energy and increase the oxygen uptake. MT was an effective biomarker, responding to copper in different pHs and dissolved oxygen. Combined-factors caused more significant disturbance in the biomarkers than single-factors.

Role of MMP9 on Invadopodia Formation in Cells From Adenoid Cystic Carcinoma. Study by Laser Scanning Confocal Microscopy

Migration, invasion and protease activity are essential for tumor progression and metastasis. Metastatic cells rely on invadopodia to degrade and invade extracellular matrix (ECM). Invadopodia are membrane protrusions with enzymes required for ECM degradation. These protrusions contain cortactin and membrane type I matrix metalloproteinase (MT1-MMP) superimposed to areas of digested matrix. Here we characterized invadopodia in a cell line (CAC2) derived from human adenoid cystic carcinoma. We carried out fluorescent-substrate degradation assay to assess in situ protease activity of CAC2 cells. Digestion spots in fluorescent substrate appear as black areas in green background. Cells were cultured on Matrigel-gelatin-FITC and fixed after 1 h and 3 h. CAC2 cells were double labeled to actin and cortactin. Cells were also double stained to actin and MT1-MMR Samples were studied by laser scanning confocal microscopy. In all time points CAC2 cells showed actin, cortactin, and MT1-MMP colocalized with digestion spots in fluorescent substrate. We searched for other proteases involved in invadopodia activity. We have previously demonstrated that MMP9 influences adenoid cystic carcinoma behavior. This prompted us to investigate role played by MMP9 on invadopodia formation. CAC2 cells had MMP9 silenced by siRNA. After I h in fluorescent substrate, cells with silenced MMP9 showed clear decrease in matrix digestion compared with controls. No differences were found in cells with silenced MMP9 grown for 3 h on fluorescent substrate. Our results showed that CAC2 cells exhibit functional invadopodia containing cortactin and MT1-MMR Furthermore, MMP9 would be required in the initial steps of invadopodia formation. Microsc. Res. Tech. 73:99-108, 2010. (C) 2009 Wiley-Liss, Inc.

Involvement of Eukaryotic Translation Initiation Factor 5A (eIF5A) in Skeletal Muscle Stem Cell Differentiation

The eukaryotic translation initiation factor 5A (eIF5A) contains a special amino acid residue named hypusine that is required for its activity, being produced by a post-translational modification using spermidine as substrate. Stem cells from rat skeletal muscles (satellite cells) were submitted to differentiation and an increase of eIF5A gene expression was observed. Higher content of eIF5A protein was found in satellite cells on differentiation in comparison to non-differentiated satellite cells and skeletal muscle. The treatment with NI-guanyl- 1,7-diaminoheptane (GC7), a hypusination inhibitor, reversibly abolished the differentiation process. In association with the differentiation blockage, an increase of glucose consumption and lactate production and a decrease of glucose and palmitic acid oxidation were observed. A reduction in cell proliferation and protein synthesis was also observed. L-Arginine, a spermidine precursor and partial suppressor of muscle dystrophic phenotype, partially abolished the GC7 inhibitory effect on satellite cell differentiation. These results reveal a new physiological role for eIF5A and contribute to elucidate the molecular mechanisms involved in muscle regeneration.

Selecting salient objects in real scenes: An oscillatory correlation model

Attention is a critical mechanism for visual scene analysis. By means of attention, it is possible to break down the analysis of a complex scene to the analysis of its parts through a selection process. Empirical studies demonstrate that attentional selection is conducted on visual objects as a whole. We present a neurocomputational model of object-based selection in the framework of oscillatory correlation. By segmenting an input scene and integrating the segments with their conspicuity obtained from a saliency map, the model selects salient objects rather than salient locations. The proposed system is composed of three modules: a saliency map providing saliency values of image locations, image segmentation for breaking the input scene into a set of objects, and object selection which allows one of the objects of the scene to be selected at a time. This object selection system has been applied to real gray-level and color images and the simulation results show the effectiveness of the system. (C) 2010 Elsevier Ltd. All rights reserved.

Generalized external indexes for comparing data partitions with overlapping categories

There is a family of well-known external clustering validity indexes to measure the degree of compatibility or similarity between two hard partitions of a given data set, including partitions with different numbers of categories. A unified, fully equivalent set-theoretic formulation for an important class of such indexes was derived and extended to the fuzzy domain in a previous work by the author [Campello, R.J.G.B., 2007. A fuzzy extension of the Rand index and other related indexes for clustering and classification assessment. Pattern Recognition Lett., 28, 833-841]. However, the proposed fuzzy set-theoretic formulation is not valid as a general approach for comparing two fuzzy partitions of data. Instead, it is an approach for comparing a fuzzy partition against a hard referential partition of the data into mutually disjoint categories. In this paper, generalized external indexes for comparing two data partitions with overlapping categories are introduced. These indexes can be used as general measures for comparing two partitions of the same data set into overlapping categories. An important issue that is seldom touched in the literature is also addressed in the paper, namely, how to compare two partitions of different subsamples of data. A number of pedagogical examples and three simulation experiments are presented and analyzed in details. A review of recent related work compiled from the literature is also provided. (c) 2010 Elsevier B.V. All rights reserved.

Exact Search Directions for Optimization of Linear and Nonlinear Models Based on Generalized Orthonormal Functions

A novel technique for selecting the poles of orthonormal basis functions (OBF) in Volterra models of any order is presented. It is well-known that the usual large number of parameters required to describe the Volterra kernels can be significantly reduced by representing each kernel using an appropriate basis of orthonormal functions. Such a representation results in the so-called OBF Volterra model, which has a Wiener structure consisting of a linear dynamic generated by the orthonormal basis followed by a nonlinear static mapping given by the Volterra polynomial series. Aiming at optimizing the poles that fully parameterize the orthonormal bases, the exact gradients of the outputs of the orthonormal filters with respect to their poles are computed analytically by using a back-propagation-through-time technique. The expressions relative to the Kautz basis and to generalized orthonormal bases of functions (GOBF) are addressed; the ones related to the Laguerre basis follow straightforwardly as a particular case. The main innovation here is that the dynamic nature of the OBF filters is fully considered in the gradient computations. These gradients provide exact search directions for optimizing the poles of a given orthonormal basis. Such search directions can, in turn, be used as part of an optimization procedure to locate the minimum of a cost-function that takes into account the error of estimation of the system output. The Levenberg-Marquardt algorithm is adopted here as the optimization procedure. Unlike previous related work, the proposed approach relies solely on input-output data measured from the system to be modeled, i.e., no information about the Volterra kernels is required. Examples are presented to illustrate the application of this approach to the modeling of dynamic systems, including a real magnetic levitation system with nonlinear oscillatory behavior.

High-frequency extensions of magnetorotational instability in astrophysical plasmas

High-frequency extensions of magnetorotational instability driven by the Velikhov effect beyond the standard magnetohydrodynamic (MHD) regime are studied. The existence of the well-known Hall regime and a new electron inertia regime is demonstrated. The electron inertia regime is realized for a lesser plasma magnetization of rotating plasma than that in the Hall regime. It includes the subregime of nonmagnetized electrons. It is shown that, in contrast to the standard MHD regime and the Hall regime, magnetorotational instability in this subregime can be driven only at positive values of dln Omega/dlnr, where Omega is the plasma rotation frequency and r is the radial coordinate. The permittivity of rotating plasma beyond the standard MHD regime, including both the Hall regime and the electron inertia regime, is calculated.

Enhancement on the Europium emission band of Europium chlortetracycline complex in the presence of LDL

Low-density lipoprotein (LDL) particles are the major cholesterol-carrying lipoprotein in the human circulation from the liver to peripheral tissues. High levels of LDL-Cholesterol (LDL-C) are known risk factor for the development of coronary artery disease (CAD). The most common approach to determine the LDLC in the clinical laboratory involves the Friedewald formula. However, in certain situations, this approach is inadequate. In this paper we report on the enhancement on the Europium emission band of Europium chlortetracycline complex (CTEu) in the presence of LDL. The emission intensity at 615 nm of the CTEu increases with increasing amounts of LDL. This phenomenon allowed us to propose a method to determine the LDL concentration in a sample composed by an aqueous solution of LDL. With this result we obtained LDL calibration curve, LOD (limit of detection) of 0.49 mg/mL and SD (standard deviation) of 0.003. We observed that CTEu complex provides a wider dynamic concentration-range for LDL determination than that from Eu-tetracycline previously. The averaged emission lifetimes of the CTEu and CTEu with LDL (1.5 mg/mL) complexes were measured as 15 and 46 Its, respectively. Study with some metallic interferents is presented. (C) 2010 Elsevier Inc. All rights reserved.

Early Increase in Autoantibodies Against Human Oxidized Low-Density Lipoprotein in Hypertensive Patients After Blood Pressure Control

BACKGROUND Oxidized lipoproteins and antioxidized low-density lipoprotein (anti-oxLDL) antibodies (Abs) have been detected in plasma in response to blood pressure (BP) elevation, suggesting the participation of the adaptive immune system. Therefore, treatment of hypertension may act on the immune response by decreasing oxidation stimuli. However, this issue has not been addressed. Thus, we have here analyzed anti-oxLDL Abs in untreated (naive) hypertensive patients shortly after initiation of anti hypertensive therapeutic regimens. METHODS Titers of anti-oxLDL Abs were measured in subjects with recently diagnosed hypertension on stage 1 (n = 94), in primary prevention of coronary disease, with no other risk factors, and naive of anti hypertensive medication at entry. Subjects were randomly assigned to receive perindopril, hydrochlorothiazide (HCTZ), or indapamide (INDA) for 12 weeks, with additional perindopril if necessary to achieve BP control. Abs against copper-oxidized LDL were measured by enzyme-linked immunosorbent assay. RESULTS Twelve-week antihypertensive treatment reduced both office-based and 24-h ambulatory BP measurements (P < 0.0005). The decrease in BP was accompanied by reduction in thiobarbituric acid-reactive substances (TBARS) (P < 0.05), increase in anti-oxLDL Ab titers (P < 0.005), and improvement in flow-mediated dilation (FMD) (P < 0.0005), independently of treatment. Although BP was reduced, we observed favorable changes in anti-oxLDL titers and FMD. CONCLUSIONS We observed that anti-oxLDL Ab titers increase after antihypertensive therapy in primary prevention when achieving BP targets. Our results are in agreement with the concept that propensity to oxidation is increased by essential hypertension and anti-oxLDL Abs may be protective and potential biomarkers for the follow-up of hypertension treatment.

D(s)D* Molecule as an Axial Meson

We use QCD sum rules to study the possible existence of a D(s)(D) over bar* - D(s)*(D) over bar molecule with the quantum number J(PC) = 1(++). We consider the contributions of condensates up to dimension eight and work at leading order in alpha(s). We obtain m(DsD*) = (3.96 +/- 0.10) GeVaround 100 MeV above the mass of the meson X(3872). The proposed state is a natural generalized state to the strangeness sector of the X(3872), which was also found to be consistent with a multiquark state from a previous QCD sum rule analysis.

The meson Z(+) (4430) as a tetraquark state

We test the validity of the QCD sum rules applied to the meson Z(+)(4430). by considering a diquark-antidiquark type of current with J(P) = 0(-) and with J(P) = 1(-). We find that, with the studied currents, it is possible to find an acceptable Borel window. In such a Borel window we have simultaneously a good OPE convergence and a pole contribution which is bigger than the continuum contribution. We get m(z) = (4.52 +/- 0.09) GeV and m(Z) = (4.84 +/- 0.14) GeV for the currents with J(P) = 0(-) and J(P) = 1(-), respectively. We conclude that the QCD sum rules results favors J(P) = 0(-) quantum numbers for the Z(+) (4430) meson. (C) 2008 Elsevier B.V. All rights reserved.

Can the pi(+) chi(c1) resonance structures be D*(D)over-bar* and D(1)(D)over-bar molecules?

We use QCD sum rules to study the recently observed resonance-like structures in the pi(+)chi(c1) mass distribution, Z(1)(+) (4050) and Z(2)(+) (4250), considered as D*(+) (D) over bar*(0) and D(1)(+) (D) over bar (0) + D(+) (D) over bar (0)(1) molecules with the quantum number J(P) = 0(+) and J(P) = 1-, respectively. We consider the contributions of condensates up to dimension eight and work at leading order in alpha(s). We obtain m(D*D*) = (4.15 +/- 0.12) GeV, around 100 MeV above the D*D* threshold, and m(D1D) = (4.19 +/- 0.22) GeV, around 100 MeV below the D(1)D threshold. We conclude that the D*(+)(D) over bar*(0) state is probably a virtual state that is not related with the Z(1)(+) (4050) resonance-like structure. In the case of the D(1)D molecular state, considering the errors, its mass is consistent with both Z(1)(+)(4050) and Z(2)(+)(4250) resonance-like structures. Therefore, we conclude that no definite conclusion can be drawn for this state from the present analysis. (C) 2008 Elsevier B.V All rights reserved.

Longitudinal scaling property of the charge balance function in Au plus Au collisions at root s(NN)=200 GeV

We present measurements of the charge balance function, from the charged particles, for diverse pseudorapidity and transverse momentum ranges in Au + Au collisions at root S(NN) = 200 GeV using the STAR detector at RHIC. We observe that the balance function is boost-invariant within the pseudorapidity coverage vertical bar-1.3, 1.3 vertical bar. The balance function properly scaled by the width of the observed pseudorapidity window does not depend on the position or size of the pseudorapidity window. This scaling property also holds for particles in different transverse momentum ranges. In addition, we find that the width of the balance function decreases monotonically with increasing transverse momentum for all centrality classes. (c) 2010 Elsevier B.V. All rights reserved.

Observation of an Antimatter Hypernucleus

Nuclear collisions recreate conditions in the universe microseconds after the Big Bang. Only a very small fraction of the emitted fragments are light nuclei, but these states are of fundamental interest. We report the observation of antihypertritons-comprising an antiproton, an antineutron, and an antilambda hyperon-produced by colliding gold nuclei at high energy. Our analysis yields 70 +/- 17 antihypertritons (3/Lambda(H) over bar) and 157 +/- 30 hypertritons ((3)(Lambda)H). The measured yields of (3)(Lambda)H (3/Lambda(H) over bar) and (3)He ((3)(He) over bar) are similar, suggesting an equilibrium in coordinate and momentum space populations of up, down, and strange quarks and antiquarks, unlike the pattern observed at lower collision energies. The production and properties of antinuclei, and of nuclei containing strange quarks, have implications spanning nuclear and particle physics, astrophysics, and cosmology.