Descripción: We study reaction-diffusion systems which involve processes that occur on different time scales. In particular, we apply a multiscale analysis to obtain a reduced description of the slow dynamics. Under certain assumptions this reduction yields a new set of reaction-diffusion equations with rescaled diffusion coefficients. We analyze the Selkov model [E. E. Selkov, Eur. J. Biochem. 4, 79 (1968)] and the ferrocyanide-iodide-sulfite reaction [E. C. Edblom et al., J. Am. Chem. Soc. 108, 2826 (1986)] to determine whether the rescaling in this case may account for the difference of diffusivities that the formation of certain types of patterns requires. © 2000 American Institute of Physics.

Descripción: Dimethyl sulfoxide (DMSO) has been known to enhance cell membrane permeability of drugs or DNA. Molecular dynamics (MD) simulations with single-component lipid bilayers predicted the existence of three regimes of action of DMSO: membrane loosening, pore formation and bilayer collapse. We show here that these modes of action are also reproduced in the presence of cholesterol in the bilayer, and we provide a description at the atomic detail of the DMSO-mediated process of pore formation in cholesterol-containing lipid membranes. We also successfully explore the applicability of DMSO to promote plasma membrane permeability to water, calcium ions (Ca2+) and Yo-Pro-1 iodide (Yo-Pro-1) in living cell membranes. The experimental results on cells in culture can be easily explained according to the three expected regimes: in the presence of low doses of DMSO, the membrane of the cells exhibits undulations but no permeability increase can be detected, while at intermediate DMSO concentrations cells are permeabilized to water and calcium but not to larger molecules as Yo-Pro-1. These two behaviors can be associated to the MD-predicted consequences of the effects of the DMSO at low and intermediate DMSO concentrations. At larger DMSO concentrations, permeabilization is larger, as even Yo-Pro-1 can enter the cells as predicted by the DMSO-induced membrane-destructuring effects described in the MD simulations. © 2012 de Ménorval et al.

Descripción: Leptin, the 16-kDa protein product of the obese gene, was originally considered as an adipocyte-derived signaling molecule for the central control of metabolism. However, leptin has been suggested to be involved in other functions during pregnancy, particularly in placenta. In the present work, we studied a possible effect of leptin on trophoblastic cell proliferation, survival, and apoptosis. Recombinant human leptin added to JEG-3 and BeWo choriocarcinoma cell lines showed a stimulatory effect on cell proliferation up to 3 and 2.4 times, respectively, measured by 3H-thymidine incorporation and cell counting. These effects were time and dose dependent. Maximal effect was achieved at 250 ng leptin/ml for JEG-3 cells and 50 ng leptin/ml for BeWo cells. Moreover, by inhibiting endogenous leptin expression with 2 μM of an antisense oligonucleotide (AS), cell proliferation was diminished. We analyzed cell population distribution during the different stages of cell cycle by fluorescence-activated cell sorting, and we found that leptin treatment displaced the cells towards a G2/M phase. We also found that leptin upregulated cyclin D1 expression, one of the key cell cycle-signaling proteins. Since proliferation and death processes are intimately related, the effect of leptin on cell apoptosis was investigated. Treatment with 2 μM leptin AS increased the number of apoptotic cells 60 times, as assessed by annexin V-fluorescein isothiocyanate/propidium iodide staining, and the caspase-3 activity was increased more than 2 fold. This effect was prevented by the addition of 100 ng leptin/ml. In conclusion, we provide evidence that suggests that leptin is a trophic and mitogenic factor for trophoblastic cells by virtue of its inhibiting apoptosis and promoting proliferation. © 2007 by the Society for the Study of Reproduction, Inc.

Descripción: Vertical excitation and electron detachment energies associated with the optical absorption of iodide ions dissolved in supercritical ammonia at 420 K have been calculated in two limiting scenarios: as a solvated free I- ion and forming a K+ I- contact ion pair (CIP). The evolution of the transition energies as a result of the gradual building up of the solvation structure was studied for each absorbing species as the solvent's density increased, i.e., changing the N H3 supercritical thermodynamic state. In both cases, if the solvent density is sufficiently high, photon absorption produces a spatially extended electron charge beyond the volume occupied by the solvated solute core; this excited state resembles a typical charge-transfer-to-solvent (CTTS) state. A combination of classical molecular dynamics simulations followed by quantum mechanical calculations for the ground, first-excited, and electron-detached electronic states have been carried out for the system consisting of one donor species (free I- ion or K+ I- CIP) surrounded by ammonia molecules. Vertical excitation and electron detachment energies were obtained by averaging 100 randomly chosen microconfigurations along the molecular dynamics trajectory computed for each thermodynamic condition (fluid density). Short- and long-range contributions of the solvent-donor interaction upon the CTTS states of I- and K+ I- were identified by performing additional electronic structure calculations where only the solvent interaction due to the first neighbor molecules was taken into account. These computations, together with previous experimental evidence that we collected for the system, have been used to analyze the solvent effects on the CTTS transition. In this paper we have established the following: (i) the CTTS electron of free I- ion or K+ I- CIP presents similar features, and it gradually localizes in close proximity of the iodine parent atom when the ammonia density is increased; (ii) for the free I- ion, the short-range solvent interaction contributes to the stabilization of the ground state more than it does for the CTTS excited state, which is evidenced experimentally as a blueshift in the maximum absorption of the CTTS transition when the density is increased; (iii) this effect is less noticeable for the K+ I- ion pair, because in this case a tight solvation structure, formed by four N H3 molecules wedged between the ions, appears at very low density and is very little affected by changes in the density; (iv) the long-range contribution to the solvent stabilization can be neglected for the K+ I- CIP, since the main features of its electronic transition can be explained on the basis of the vicinity of the cation; (v) however, the long-range solvent field contribution is essential for the free I- ion to become an efficient CTTS donor upon photoexcitation, and this establishes a difference in the CTTS behavior of I- in bulk and in clusters. © 2007 American Institute of Physics.