MFG-E8/lactadherin regulates cyclins D1/D3 expression and enhances the tumorigenic potential of mammary epithelial cells.

Milk fat globule-EGF factor 8 (MFG-E8) is a glycoprotein highly expressed in breast cancer that contributes to tumor progression through largely undefined mechanisms. By analyzing publicly available gene expression profiles of breast carcinomas, we found that MFG-E8 is highly expressed in primary and metastatic breast carcinomas, associated with absent estrogen receptor expression. Immunohistochemistry analysis of breast cancer biopsies revealed that MFG-E8 is expressed on the cell membrane as well as in the cytoplasm and nucleus. We also show that increased expression of MFG-E8 in mammary carcinoma cells increases their tumorigenicity in immunodeficient mice, and conversely, its downregulation reduces their in vivo growth. Moreover, expression of MFG-E8 in immortalized mammary epithelial cells promotes their growth and branching in three-dimensional collagen matrices and induces the expression of cyclins D1/D3 and N-cadherin. A mutant protein unable to bind integrins can in part exert these effects, indicating that MFG-E8 function is only partially dependent on integrin activation. We conclude that MFG-E8-dependent signaling stimulates cell proliferation and the acquisition of mesenchymal properties and contributes to mammary carcinoma development.

Nutrient supply by mass flow and diffusion to maize plants in response to soil aggregate size and water potential

Nutrients are basically transported to the roots by mass flow and diffusion. The aim of this study was to quantify the contribution of these two mechanisms to the acquisition of macronutrients (N, P, K, Ca, Mg, and S) and cationic micronutrients (Fe, Mn, Zn, and Cu) by maize plants as well as xylem exudate volume and composition in response to soil aggregate size and water availability. The experiment was conducted in a greenhouse with samples of an Oxisol, from under two management systems: a region of natural savanna-like vegetation (Cerradão, CER) and continuous maize under conventional management for over 30 years (CCM). The treatments were arranged in a factorial [2 x (1 + 2) x 2] design, with two management systems (CER and CCM), (1 + 2) soil sifted through a 4 mm sieve and two aggregate classes (< 0.5 mm and 0.5 - 4.0 mm) and two soil matric potentials (-40 and -10 kPa). These were evaluated in a randomized block design with four replications. The experiment was conducted for 70 days after sowing. The influence of soil aggregate size and water potential on the nutrient transport mechanisms was highest in soil samples with higher nutrient concentrations in solution, in the CER system; diffusion became more relevant when water availability was higher and in aggregates < 0.5 mm. The volume of xylem exudate collected from maize plants increased with the decrease in aggregate size and the increased availability of soil water in the CER system. The highest Ca and Mg concentrations in the xylem exudate of plants grown on samples from the CER system were related to the high concentrations of these nutrients in the soil solution of this management system.

Enantiomers' potential in psychopharmacology--a critical analysis with special emphasis on the antidepressant escitalopram

Stereochemistry is now influencing most areas of pharmacotherapy, with a growing awareness in the field of psychiatry and, more specifically, depression. This is due to the fact that the enantiomers of many chiral drugs may have distinct pharmacological, pharmacokinetic and/or pharmacogenetic profiles. Consequently, in some instances there may be an advantage in using a single enantiomer over the racemic form-thus providing a basis for the development of new therapeutic agents, as well as the potential to improve current treatments. This review highlights some of the potential advantages and disadvantages that using single enantiomers might offer. The principles are exemplified through reference to the stereoselective properties of several established chiral psychotropic drugs, including thioridazine, methadone, trimipramine, mianserin, mirtazapine, fluoxetine and citalopram. Emphasis is given to the treatment of depression and how the potential of one pure enantiomer-escitalopram, the S-enantiomer of the selective serotonin reuptake inhibitor citalopram-appears to be fulfilling its preclinical promise in the clinic.

Coculture of bladder urothelial and smooth muscle cells on small intestinal submucosa: potential applications for tissue engineering technology.

PURPOSE: Small intestinal submucosa is a xenogenic, acellular, collagen rich membrane with inherent growth factors that has previously been shown to promote in vivo bladder regeneration. We evaluate in vitro use of small intestinal submucosa to support the individual and combined growth of bladder urothelial cells and smooth muscle cells for potential use in tissue engineering techniques, and in vitro study of the cellular mechanisms involved in bladder regeneration. MATERIALS AND METHODS: Primary cultures of human bladder urothelial cells and smooth muscle cells were established using standard enzymatic digestion or explant techniques. Cultured cells were then seeded on small intestinal submucosa at a density of 1 x 105 cells per cm.2, incubated and harvested at 3, 7, 14 and 28 days. The 5 separate culture methods evaluated were urothelial cells seeded alone on the mucosal surface of small intestinal submucosa, smooth muscle cells seeded alone on the mucosal surface, layered coculture of smooth muscle cells seeded on the mucosal surface followed by urothelial cells 1 hour later, sandwich coculture of smooth muscle cells seeded on the serosal surface followed by seeding of urothelial cells on the mucosal surface 24 hours later, and mixed coculture of urothelial cells and smooth muscle cells mixed and seeded together on the mucosal surface. Following harvesting at the designated time points small intestinal submucosa cell constructs were formalin fixed and processed for routine histology including Masson trichrome staining. Specific cell growth characteristics were studied with particular attention to cell morphology, cell proliferation and layering, cell sorting, presence of a pseudostratified urothelium and matrix penetrance. To aid in the identification of smooth muscle cells and urothelial cells in the coculture groups, immunohistochemical analysis was performed with antibodies to alpha-smooth muscle actin and cytokeratins AE1/AE3. RESULTS: Progressive 3-dimensional growth of urothelial cells and smooth muscle cells occurred in vitro on small intestinal submucosa. When seeded alone urothelial cells and smooth muscle cells grew in several layers with minimal to no matrix penetration. In contrast, layered, mixed and sandwich coculture methods demonstrated significant enhancement of smooth muscle cell penetration of the membrane. The layered and sandwich coculture techniques resulted in organized cell sorting, formation of a well-defined pseudostratified urothelium and multilayered smooth muscle cells with enhanced matrix penetration. With the mixed coculture technique there was no evidence of cell sorting although matrix penetrance by the smooth muscle cells was evident. Immunohistochemical studies demonstrated that urothelial cells and smooth muscle cells maintain the expression of the phenotypic markers of differentiation alpha-smooth muscle actin and cytokeratins AE1/AE3. CONCLUSIONS: Small intestinal submucosa supports the 3-dimensional growth of human bladder cells in vitro. Successful combined growth of bladder cells on small intestinal submucosa with different seeding techniques has important future clinical implications with respect to tissue engineering technology. The results of our study demonstrate that there are important smooth muscle cell-epithelial cell interactions involved in determining the type of in vitro cell growth that occurs on small intestinal submucosa. Small intestinal submucosa is a valuable tool for in vitro study of the cell-cell and cell-matrix interactions that are involved in regeneration and various disease processes of the bladder.

Generic finite-size enhancement of pairing in mesoscopic Fermi systems

The finite-size-dependent enhancement of pairing in mesoscopic Fermi systems is studied under the assumption that the BCS approach is valid and that the two-body force is size independent. Different systems are investigated such as superconducting metallic grains and films as well as atomic nuclei. It is shown that the finite size enhancement of pairing in these systems is in part due to the presence of a surface which accounts quite well for the data of nuclei and explains a good fraction of the enhancement in Al grains.

Antikaon potential in hot and dense matter

The antikaon optical potential in hot and dense nuclear matter is studied within the framework of a coupled-channel self-consistent calculation taking, as bare meson-baryon interaction, the meson-exchange potential of the Jlich group. Typical conditions found in heavy-ion collisions at GSI are explored. As in the case of zero temperature, the angular momentum components larger than L=0 contribute significantly to the finite temperature antikaon optical potential at finite momentum. It is found that the particular treatment of the medium effects has a strong influence on the behavior of the antikaon potential with temperature. Our self-consistent model, in which antikaons and pions are dressed in the medium, gives a moderately temperature dependent antikaon potential which remains attractive at GSI temperatures, contrary to what one finds if only nuclear Pauli blocking effects are included.

Bulk and single-particle properties of hyperonic matter at finite temperature

Bulk and single-particle properties of hot hyperonic matter are studied within the Brueckner-Hartree-Fock approximation extended to finite temperature. The bare interaction in the nucleon sector is the Argonne V18 potential supplemented with an effective three-body force to reproduce the saturating properties of nuclear matter. The modern Nijmegen NSC97e potential is employed for the hyperon-nucleon and hyperon-hyperon interactions. The effect of temperature on the in-medium effective interaction is found to be, in general, very small and the single-particle potentials differ by at most 25% for temperatures in the range from 0 to 60 MeV. The bulk properties of infinite matter of baryons, either nuclear isospin symmetric or a Beta-stable composition that includes a nonzero fraction of hyperons, are obtained. It is found that the presence of hyperons can modify the thermodynamical properties of the system in a non-negligible way.

Average ground-state energy of finite Fermi systems

Semiclassical theories such as the Thomas-Fermi and Wigner-Kirkwood methods give a good description of the smooth average part of the total energy of a Fermi gas in some external potential when the chemical potential is varied. However, in systems with a fixed number of particles N, these methods overbind the actual average of the quantum energy as N is varied. We describe a theory that accounts for this effect. Numerical illustrations are discussed for fermions trapped in a harmonic oscillator potential and in a hard-wall cavity, and for self-consistent calculations of atomic nuclei. In the latter case, the influence of deformations on the average behavior of the energy is also considered.

Albert Lewin. Pandora and the Flying Dutchman: the Semiologic Potential of a Greek Myth

Albert Lewin, a well-known Hollywood cinema director who is significantly influenced by the surrealistic movement, brings together the myth f Pandora and the legend of the flying Dutchman in order to create an exemplary love story, a crazy love story which goes beyond the limits of human reason. Bearing in mind, then, that if one wants to believe in this sort of love story must not be guided by human reason stricto sensu, he builds a world of signs, a semiologic world which this article aims at helping to interpret.

Accumulation of phosphorus fractions and contamination potential in vineyard soils in the southern region of the state of Santa Catarina, Brazil

In vineyards, if phosphate is applied both before planting and at intervals during growth without consideration of technical criteria, the soil P fractions may be increased and their proportions altered. This study was carried out to evaluate the accumulation of P fractions and the parameters of the adsorption isotherm in a sandy Typic Hapludalf soil in vineyards with a history of successive and excessive phosphate fertilization. In December 2010, two vineyards were selected, one 4 and the other 15 years old, in Urussanga, State of Santa Catarina (Brazil). Three trenches were dug in each area and soil was collected from the 0-5, 5-10 and 10-20 cm depth ranges. The soil samples were dried in a forced-air oven, sieved and subjected to chemical analyses, P chemical fractionation and P adsorption isotherms. Excessive phosphate fertilization, before and during cultivation, particularly in the older vineyard and, consequently, with a longer history of phosphate fertilization, increased the inorganic P concentrations to the depth of 20 cm, especially in labile fractions extracted by anion exchange resin and NaHCO3 in the non-labile fraction, as well as in the non-labile fraction extracted by 1.0 mol L-1 HCl. The application of phosphate fertilizers and the long cultivation period increased the P levels in the organic labile fraction extracted by 0.5 mol L-1 NaHCO3, and especially in the moderately labile fraction extracted by 0.1 and 0.5 mol L-1 NaOH. Phosphate fertilization of older vineyards, i.e., cultivated for 15 years, increased the amounts of P desorbed in water, indicating a risk of contamination of surface waters and groundwater. The phosphate fertilization before planting, without considering the results of soil analysis, and during cultivation, disregarding the results of soil analysis, leaf analysis and expected yield, led to a reduction in the maximum P adsorption capacity in the 0-5 cm layer of vineyard 2, indicating saturation of part of the reactive particle adsorption sites.

Frequency-dependent attenuation as a potential indicator of oil saturation

At seismic frequencies, wave-induced fluid flow is a major cause of P-wave attenuation in partially saturated porous rocks. Attenuation is of great importance for the oil industry in the interpretation of seismic field data. Here, the effects on P-wave attenuation resulting from changes in oil saturation are studied for media with coexisting water, oil, and gas. For that, creep experiments are numerically simulated by solving Biot's equations for consolidation of poroelastic media with the finite-element method. The experiments yield time-dependent stress?strain relations that are used to calculate the complex P-wave modulus from which frequency-dependent P-wave attenuation is determined. The models are layered media with periodically alternating triplets of layers. Models consisting of triplets of layers having randomly varying layer thicknesses are also considered. The layers in each triplet are fully saturated with water, oil, and gas. The layer saturated with water has lower porosity and permeability than the layers saturated with oil and gas. These models represent hydrocarbon reservoirs in which water is the wetting fluid preferentially saturating regions of lower porosity. The results from the numerical experiments showed that increasing oil saturation, connected to a decrease in gas saturation, resulted in a significant increase of attenuation at low frequencies (lower than 2 Hz). Furthermore, replacing the oil with water resulted in a distinguishable behavior of the frequency-dependent attenuation. These results imply that, according to the physical mechanism of wave-induced fluid flow, frequency-dependent attenuation in media saturated with water, oil, and gas is a potential indicator of oil saturation.

Vacuum decay in quantum field theory

We study the contribution to vacuum decay in field theory due to the interaction between the long- and short-wavelength modes of the field. The field model considered consists of a scalar field of mass M with a cubic term in the potential. The dynamics of the long-wavelength modes becomes diffusive in this interaction. The diffusive behavior is described by the reduced Wigner function that characterizes the state of the long-wavelength modes. This function is obtained from the whole Wigner function by integration of the degrees of freedom of the short-wavelength modes. The dynamical equation for the reduced Wigner function becomes a kind of Fokker-Planck equation which is solved with suitable boundary conditions enforcing an initial metastable vacuum state trapped in the potential well. As a result a finite activation rate is found, even at zero temperature, for the formation of true vacuum bubbles of size M-1. This effect makes a substantial contribution to the total decay rate.

Finite-size effects in nonequilibrium correlation functions

We have shown that finite-size effects in the correlation functions away from equilibrium may be introduced through dimensionless numbers: the Nusselt numbers, accounting for both the nature of the boundaries and the size of the system. From an analysis based on fluctuating hydrodynamics, we conclude that the mean-square fluctuations satisfy scaling laws, since they depend only on the dimensionless numbers in addition to reduced variables. We focus on the case of diffusion modes and describe some physical situations in which finite-size effects may be relevant.

Mean first-passage time for system driven by the coin-toss square wave

We study the mean-first-passage-time problem for systems driven by the coin-toss square-wave signal. Exact analytic solutions are obtained for the driftless case. We also obtain approximate solutions for the potential case. The mean-first-passage time exhibits discontinuities and a remarkable nonsmooth oscillatory behavior which, to our knowledge, has not been observed for other kinds of driving noise.

Analytic behavior of the QED polarizability function at finite temperature

We revisit the analytical properties of the static quasi-photon polarizability function for an electron gas at finite temperature, in connection with the existence of Friedel oscillations in the potential created by an impurity. In contrast with the zero temperature case, where the polarizability is an analytical function, except for the two branch cuts which are responsible for Friedel oscillations, at finite temperature the corresponding function is non analytical, in spite of becoming continuous everywhere on the complex plane. This effect produces, as a result, the survival of the oscillatory behavior of the potential. We calculate the potential at large distances, and relate the calculation to the non-analytical properties of the polarizability.