Properties and Potential Antiproliferative Activity of Thrombin-Binding Aptamer (TBA) Derivatives with One or Two Additional G-Tetrads

In this paper, we study the biological properties of two TBA analogs containing one and two extra G-tetrads, namely TBAG3 and TBAG4, respectively, and two further derivatives in which one of the small loops at the bottom (TBAG41S) or the large loop at the top (TBAG4GS) of the TBAG4 structure has been completely modified by replacing all loop residues with abasic site mimics. The therapeutical development of the TBA was hindered by its low thermodynamic and nuclease stability, while its potential as an anticancer/antiproliferative molecule is also affected by the anticoagulant activity, being a side effect in this case. In order to obtain suitable TBA analogs and to explore the involvement of specific aptamer regions in biological activity, the antiproliferative capability against DU 145 and MDAMB 231 cancer cell lines (MTT), the anticoagulant properties (PT), the biological degradability (nuclease stability assay) and nucleolin (NCL) binding ability (SPR) of the above described TBA derivatives have been tested. Interestingly, none of the TBA analogs exhibits an anticoagulant activity, while all of them show antiproliferative properties to the same extent. Furthermore, TBAG4 displays extraordinary nuclease stability and promising antiproliferative properties against breast cancer cells binding NCL efficiently. These results expand the range of G4-structures targeting NCL and the possibility of developing novel anticancer and antiviral drugs.     

Coprecipitation of arsenate with metal oxides: nature, mineralogy, and reactivity of aluminum precipitates

Arsenic mobilization in soils is mainly controlled by sorption/desorption processes, but arsenic also may be coprecipitated with aluminum and/or iron in natural environments. Although coprecipitation of arsenic with aluminum and iron oxides is an effective treatment process for arsenic removal from drinking water, the nature and reactivity of aluminum- or iron-arsenic coprecipitates has received little attention. We studied the mineralogy, chemical composition, and surface properties of aluminum-arsenate coprecipitates, as well as the sorption of phosphate on and the loss of arsenate from these precipitates. Aluminum-arsenate coprecipitates were synthesized at pH 4.0, 7.0, or 10.0 and As/Al molar ratio (R) of 0, 0.01, or 0.1 and were aged 30 or 210 d at 50 degrees C. In the absence of arsenate, gibbsite (pH 4.0 or 7.0) and bayerite (pH 10.0) formed, whereas in the presence of arsenate, very poorly crystalline precipitates formed. Short-range ordered materials (mainly poorly crystalline boehmite) formed at pH 4.0 (R = 0.01 and 0.1), 7.0, and 10.0 (R= 0.1) and did not transform into Al(OH)3 polymorphs even after prolonged aging. The surface properties and chemical composition of the aluminum precipitates were affected by the initial pH, R, and aging. Chemical dissolution of the samples by 6 mol L(-1) HCl and 0.2 mol L(-1) oxalic acid/ oxalate solution indicated that arsenate was present mainly in the short-range ordered precipitates. The sorption of phosphate onto the precipitates was influenced by the nature of the samples and the amounts of arsenate present in the precipitates. Large amounts of phosphate partially replaced arsenate only from the samples formed at R = 0.1. The quantities of arsenate desorbed from these coprecipitates by phosphate increased with increasing phosphate concentration, reaction time, and precipitate age butwere always lessthan 30% of the amounts of arsenate present in the materials and were particularly low (<4%) from the sample prepared at pH 4.0. Arsenate appeared to be occluded within the network of short-range ordered materials and/or sorbed onto the external surfaces of the precipitates, but sorption on the external surfaces seemed to increase by increasing pH of sample preparation and aging. Furthermore, at pH 4.0 more than in neutral or alkaline systems the formation of aluminum arsenate precipitates seemed to be favored. Finally, we have observed that greater amounts of phosphate were sorbed on an aluminum-arsenate coprecipitate than on a preformed aluminum oxide equilibrated with arsenate under the same conditions (R = 0.1, pH 7.0). In contrast, the opposite occurred for arsenate desorption, which was attributed to the larger amounts of arsenate occluded in the coprecipitate.     

ICA based identification of dynamical systems generating synthetic and real world time series

Independent Component Analysis (ICA) is a recent and well known technique used to separate mixtures of signals. While in general the researchers put their attention on the type of signals and of mixing, we focus our attention on a quite general class of models which act as sources of the time series, the dynamical systems. In this paper we focus our attention on the general problem to understand the behaviour of ICA methods with respect to the time series deriving from a specific dynamical system, selecting large classes of them, and using ICA to make separation. This study gives some interesting results that are very useful both to highlight some properties related to dynamical systems and to clarify some general aspects of ICA, by using both synthetic and real data. From one hand we study the features of the linear (simple and coupled) and non-linear (single and coupled) dynamical systems, stochastic resonances, chaotic and real dynamical systems. We have to stress that we obtain information about the separation of these systems and substantially how from the entropy of the complete system we can obtain the entropies of the single dynamical systems (so that we also could obtain a more realistic analogic circuit). On the other hand these results show the high capability of the ICA method to recognize the dynamical systems independently from their complexity and in the case of stochastic series ICA perfectly recognizes the different dynamical systems also where the Fourier Transform is irresolute. We also note that in the case of real dynamical systems we showed that ICA permits to recognize the information connected to the sources and to associate to it a phenomenological dynamical system that reproduce it (i.e. Organ Pipe, Stromboli Volcano, Aerosol Index).     

Modelling Trust in Artificial Agents, A First Step Toward the Analysis of e-Trust

This paper provides a new analysis of e-trust, trust occurring in digital contexts, among the artificial agents of a distributed artificial system. The analysis endorses a non-psychological approach and rests on a Kantian regulative ideal of a rational agent, able to choose the best option for itself, given a specific scenario and a goal to achieve. The paper first introduces e-trust describing its relevance for the contemporary society and then presents a new theoretical analysis of this phenomenon. The analysis first focuses on an agent’s trustworthiness, this one is presented as the necessary requirement for e-trust to occur. Then, a new definition of e-trust as a second-order-property of first-order relations is presented. It is shown that the second-order-property of e-trust has the effect of minimising an agent’s effort and commitment in the achievement of a given goal. On this basis, a method is provided for the objective assessment of the levels of e-trust occurring among the artificial agents of a distributed artificial system.     

Fatty acid mobilized by the vascular endothelial growth factor in human endothelial cells

Release of FFA from membrane phospholipids was observed after incubation of umbilical cord vein-derived endothelial cells (HUVEC) with vascular endothelial growth factor (VEGF). In particular, we found an increase of arachidonate, stearate, and palmitate in a time-dependent manner with a peak at 30 min. The maximum increase was reached by arachidonate (4.4-fold), followed by stearate (2.2-fold) and palmitate (1.3-fold). The arachidonate increase can be ascribed to the activation of phospholipase A₂ (PLA₂). In fact, cells preincubated with arachidonyl trifluoromethyl ketone, a PLA₂ inhibitor, showed a marked reduction in arachidonate mobilization. The role of Ca²⁺ in PLA₂ activation was also investigated. Cells incubated with VEGF in the presence of EGTA showed a marked decrease in arachidonate mobilization, whereas incubation with the calcium ionophore A23187 alone produced an increase in arachidonate, although to a lesser extent compared with the VEGF stimulation. Incubation with A23187 in association with PMA produced the same increase in arachidonate as the VEGF treatment. Mitogen-activated protein kinase (MAPK) activity was also found to increase as a consequence of VEGF stimulation. Taken together, these results suggest that the VEGF-mediated activation of PLA₂ in HUVEC is dependent on both MAPK-mediated phosphorylation and Ca²⁺ increase. Furthermore, the increase in stearate and palmitate likely is brought about by the activation of a pathway involving phospholipase D, phosphatidate phosphohydrolase (PAP), and DAG lipase. In fact, the increase in those FFA was prevented when HUVEC were stimulated with VEGF in the presence of ethanol (which inhibits the formation of phosphatidate), propranolol (a specific inhibitor of PAP), or RHC-80267 (a specific inhibitor of DAG lipase).     

Application of the SBAS-DInSAR technique to fault creep: A case study of the Hayward fault, California

We present a quantitative assessment of the capability of the differential SAR interferometry (DInSAR) technique referred to as Small BAseline Subset (SBAS) approach to investigate fault creep phenomena. In particular we have computed, via the SBAS-DInSAR algorithm, time series of the surface displacements relevant to the Hayward fault zone, within the San Francisco Bay Area (California), from the European Space Agency's ERS-1/2 satellite radar data for the 1992 to 2000 time period. Starting from the DInSAR time series we measured the relative displacements across the fault with no need for any atmospheric filtering step. These results have been systematically compared to the measurements available from the alignment arrays that are located along the fault. Our analysis shows that the standard deviation of the differences between the DInSAR and the in situ measurements is on the order of 2 mm. Moreover, the estimated mean deformation rates have an accuracy that is better than 1 mm/year.     

Transport Properties of Modified Montmorillonite‐Poly(ε‐caprolactone) Nanocomposites

A series of montmorillonite‐poly(ε‐caprolactone) nanocomposites were prepared according to a two‐stage procedure. In the first step Na‐type silicate clay was cation exchanged with protonated 12‐aminolauric acid. In the second step ε‐caprolactone was intercalated in the modified clay and ring‐opening polymerized. The clay content was varied regularly from 0 to 44 wt.‐%, with exfoliation of the silicate layers being detected by X‐ray diffraction in the nanocomposites dispersing up to at least 16 wt.‐% clay. Crystallization of poly(ε‐caprolactone) was not prevented in the nanocomposites, although it proceeded to a lower extent/order than in a homopolymer sample. The transport properties were investigated using water or dichloromethane as vapor permeants. In each case, a dual sorption behavior was observed as a function of the vapor activity because of the occurrence of different sorption mechanisms. The permeability of the nanocomposites to either permeant decreased with increasing clay content. In particular, the permeability behavior to water was largely dominated by the diffusion parameter.     

5-Hydroxytryptamine Modulates Maturation and Mitochondria Function of Human Oligodendrocyte Progenitor M03-13 Cells

Inside the adult CNS, oligodendrocyte progenitor cells (OPC_S) are able to proliferate, migrate and differentiate into mature oligodendrocytes (OLs) which are responsible for the production of myelin sheet and energy supply for neurons. Moreover, in demyelinating diseases, OPCs are recruited to the lesion areas where they undergo differentiation and myelin synthesis. Serotonin (5-hydroxytryptamine, 5-HT) is involved in OLs’ development and myelination, but so far the molecular mechanisms involved or the effects of 5-HT on mitochondria function have not yet been well documented. Our data show that 5-HT inhibits migration and proliferation committing cells toward differentiation in an immortalized human oligodendrocyte precursor cell line, M03-13. Migration blockage is mediated by reactive oxygen species (ROS) generation since antioxidants, such as Vit C and Cu-Zn superoxide dismutase, prevent the inhibitory effects of 5-HT on cell migration. 5-HT inhibits OPC migration and proliferation and increases OL phenotypic markers myelin basic protein (MBP) and Olig-2 via protein kinase C (PKC) activation since the inhibitor of PKC, bis-indolyl-maleimide (BIM), counteracts 5-HT effects. NOX inhibitors as well, reverse the effects of 5-HT, indicating that 5-HT influences the maturation process of OPCs by NOX-dependent ROS production. Finally, 5-HT increases mitochondria function and antioxidant activity. The identification of the molecular mechanisms underlying the effects of 5-HT on maturation and energy metabolism of OPCs could pave the way for the development of new treatments for autoimmune demyelinating diseases such as Multiple Sclerosis where oligodendrocytes are the primary target of immune attack.