José Manuel López

Collagenase 2 (MMP-8) Expression in Murine Tissue-remodeling Processes ANALYSIS OF ITS POTENTIAL ROLE IN POSTPARTUM INVOLUTION OF THE UTERUS

Neutrophil collagenase or collagenase 2 (MMP-8) is unique among the family of matrix metalloproteinases (MMPs) because of its exclusive pattern of expression in inflammatory conditions. At present, no evidence of the occurrence of this enzyme in tissues other than human has been reported. In this work, we have cloned the murine homologue of human collagenase 2. The isolated cDNA contains an open reading frame coding for a polypeptide of 465 amino acids, which is 74% identical to its human counterpart. The mouse collagenase 2 exhibits the domain structure characteristic of several MMPs, including a signal sequence, a prodomain with the cysteine residue essential for enzyme latency, an activation locus with the Zinc-binding site, and a COOH-terminal fragment with sequence similarity to hemopexin. It also contains the three conserved residues (Tyr-209, Asp-230, and Gly-232) located around the Zinc-binding site and are distinctive of the collagenase subfamily. Northern blot analysis of RNAs isolated from a variety of mouse tissues revealed that collagenase 2 is expressed at late stages during mouse embryogenesis, coinciding with the appearance of hematopoietic cells. In addition, collagenase 2 was highly expressed in the postpartum uterus starting at 1 day postpartum and extending up to 5 days. Enzymatic analysis revealed that matrilysin, another MMP overexpressed in uterine tissue, is able to activate murine procollagenase 2. These data suggest that both enzymes could form an activation cascade resulting in the generation of the collagenolytic activity required during the process of massive connective tissue resumption occurring in the involuting uterus.

Collagenase-3 (MMP-13) Expression in Chondrosarcoma Cells and Its Regulation by Basic Fibroblast Growth Factor

Human collagenase-3 (MMP-13) is a member of the matrix metalloproteinase family of enzymes that was originally identified in breast carcinomas and subsequently detected during fetal ossification and in arthritic processes. In this work, we have found that collagenase-3 is produced by HCS-2/8 human chondrosarcoma cells. An analysis of the ability of different cytokines and growth factors to induce the expression of collagenase-3 in these cells revealed that basic fibroblast growth factor (bFGF or FGF-2) strongly up-regulated the expression of this gene. By contrast, other factors, including interleukin-1beta and transforming growth factor-beta, previously found to induce collagenase-3 expression in other cell types, did not exhibit any effect on the expression of this gene in chondrosarcoma cells. Further analysis of the bFGF-induced expression of collagenase-3 in human chondrosarcoma cells revealed that its effect was time and dose dependent, but independent of the de novo synthesis of proteins. Western blot analysis revealed that the up-regulatory effect of bFGF on collagenase-3 was also reflected at the protein level as demonstrated by the increase of immunoreactive protein in the conditioned medium of HCS-2/8 cells treated with bFGF. Immunohistochemical analysis of the presence of collagenase-3 in a series of 8 benign and 16 malignant cartilage-forming neoplasms revealed that all analyzed malignant chondrosarcomas stained positively for collagenase-3, whereas only 2 of 8 benign lesions produced this protease. In addition, the finding that bFGF was detected in all analyzed chondrosarcomas, together with the above in vitro studies on HCS-2/8 cells, suggest that this growth factor may be an in vivo modulator of collagenase-3 expression in these malignant tumors. These results extend the pattern of tumor types with ability to produce this matrix metalloproteinase and suggest that collagenase-3 upregulation may contribute to the progression of human chondrosarcomas.

Glass formation in binary alloy systems: a prediction of the composition range

Abstract A semi-empirical theory is used to calculate the composition range of binary amorphous alloys. The theory is based on the comparison of the free energies of the amorphous alloy and competing crystalline phases: terminal solid solutions and intermetallic compounds with simple structures. The enthalpy of formation of the solid solution is expressed as a sum of two contributions: a chemical contribution arising from electronic redistribution in forming the alloy, and an elastic contribution arising from the difference in size between solute and solvent atoms. The enthalpy of formation of the amorphous phase has only the chemical contribution. The theory clearly shows the key role that atomic size mismatch plays in determining the glass-forming concentration range, which is successfully computed for an illustrative sample of binary alloy systems. A connection of our treatment with the work of other authors is also provided.

Dynamical properties of liquid Al near melting: An orbital-free molecular dynamics study

The static and dynamic structure of liquid Al is studied using the orbital free ab initio molecular dynamics method. Two thermodynamic states along the coexistence line are considered, namely T=943 and 1323 K, for which x-ray and neutron scattering data are available. A kinetic-energy functional which fulfills a number of physically relevant conditions is employed, along with a local first-principles pseudopotential. In addition to a comparison with experiment, we also compare our ab initio results with those obtained from conventional molecular-dynamics simulations using effective interionic pair potentials derived from second-order pseudopotential perturbation theory.

Ab initio calculations of structures and stabilities of (NaI) nNa1 and ( CsI) nCs1 cluster ions

Ab initio calculations using the Perturbed Ion model, with correlation contributions included, are presented for nonstoichiometric (NaI)_nNa+ and (CsI)_nCs+ (n=1-14) cluster ions. The ground state and several low-lying isomers are identified and described. Rocksalt ground states are common and appear at cluster sizes lower than in the corresponding neutral systems. The most salient features of the measured mobilities seem to be explained by arguments related to the changes of the compactness of the clusters as a function of size. The stability of the cluster ions against evaporation of a single alkali halide molecule shows variations that explain the enhanced stabilities found experimentally for cluster sizes n=4, 6, 9, and 13. Finally, the ionization energies and the orbital eigenvalue spectrum of two (NaI)_13Na+ isomers are calculated and shown to be a fingerprint of the structure.

Structural, dynamic, and electronic properties of liquid tin: An ab initio molecular dynamics study

We report on a study of several structural, dynamic, and electronic properties of liquid Sn at a thermodynamic state close to the triple point (573 K) and another one at a higher temperature (1273 K). This study has been performed by ab initio molecular dynamics simulations using 205 atoms and around 20 ps of simulation time. The calculated static structures show a good agreement with the available experimental data. The dynamic structure factors fairly agree with their experimental counterparts obtained by inelastic x-ray scattering experiments, which display inelastic side peaks. The calculated dispersion relations exhibit a positive dispersion, although not so marked as suggested by the experiment; moreover, its slope at the long-wavelength limit compares favorably with the experimental sound velocity. Electron densities near selected triplets of atoms are similar to those appearing in the solid phases, but these features have an extremely short lifetime, so they should not be considered as solid remnants in the melt.

Calculation of the Band Gap Energy and Study of Cross Luminescence in Alkaline-Earth Dihalide Crystals

The band gap energy as well as the possibility of cross luminescence processes in alkaline-earth dihalide crystals have been calculated using the ab initio Perturbed-Ion (PI) model. The gap is calculated in several ways: as a difference between one-electron energy eigenvalues and as a difference between total energies of appropriate electronic states of the crystal, both at the HF level and with inclusion of Coulomb correlation effects. In order to study the possibility of ocurrence of cross luminescence in these materials, the energy difference between the valence band and the outermost core band for some representative crystals has been calculated. Both calculated band gap energies and cross luminescence predictions compare very well with the available experimental and theoretical results.

Early Stages of Bone Fracture Healing: Formation of a Fibrin–Collagen Scaffold in the Fracture Hematoma

This work is concerned with the sequence of events taking place during the first stages of bone fracture healing, from bone breakup until the formation of early fibrous callus (EFC). The latter provides a scaffold over which subsequent remodeling processes will eventually result in successful bone repair. Specifically, some mathematical models are proposed to estimate the time required for (1) the formation immediately after fracture of a fibrin clot, described in terms of a phase transition in a polymerization process, and (2) the onset of EFC which is produced when fibroblasts arising from differentiation of chemotactically recruited mesenchymal stem cells remodel a previous fibrin clot by releasing a collagen matrix over it. An attempt has been made to keep models as simple as possible, so that a explicit dependence of the estimates obtained on relevant biochemical parameters involved is obtained.

LATTICE DISTORTIONS AROUND A TL+ IMPURITY IN NAI:TL+ AND CSI:TL+ SCINTILLATORS : AN AB INITIO STUDY INVOLVING LARGE ACTIVE CLUSTERS

Ab initio perturbed ion cluster-in-the-lattice calculations of the impurity centers NaI:Tl 1 and CsI:Tl 1 are presented. We study several active clusters of increasing complexity and show that the lattice relaxation around the Tl 1 impurity implies the concerted movement of several shells of neighbors. The results also reveal the importance of considering a set of ions that can respond to the geometrical displacements of the inner shells by adapting self-consistently their wave functions. Comparison with other calculations involving comparatively small active clusters serves to assert the significance of our conclusions. Contact with experiment is made by calculating absorption energies. These are in excellent agreement with the experimental data for the most realistic active clusters considered. @S0163-1829~98!09741-0#

A mathematical model for the growth of elongated bones

A mathematical model to describe the process of formation of bone tissue by replacement of cartilage tissue is presented and discussed. This model is based on an absorption-diffusion system which describes the interaction of two key signalling molecules. These molecules characterize the dynamics of the transition zone between the cartilage and the bone tissue. Some experimental data are needed to estimate some model parameters. We discuss nhow our results are essentially unaffected by small variations, and in a particular case, not necessarily small variations in the experimental values.