Showing papers by "University of Montpellier published in 1990"

Overexpression of transfected cathepsin D in transformed cells increases their malignant phenotype and metastatic potency.

Abstract: Cathepsin D, an aspartic lysosomal proteinase, is overexpressed by breast cancer cells and highly correlated with the occurrence of metastasis in patients. We used an adenovirus transformed rat cell line that does not secrete cathepsin D, to study the consequences of transfecting human cathepsin D cDNA. Overexpression of human cathepsin D in stable transfectant clones, results in higher initial growth rates in low serum conditions, overgrowth at high cell densities resulting in stellate aggregates, and greater anchorage-independent growth in soft agar. The metastatic activity (mostly in liver) of cathepsin D clones injected into athymic mice was significantly higher than that of control clones. These results show that overexpression of cathepsin D increases the transformed phenotype of malignant cells in vitro and their metastatic potency in vivo.

The ecological consequences of flowering asynchrony in monoecious figs: a simulation study'

Abstract: For plants with temporally separate sexual phases to outcross, population- level flowering asynchrony is necessary, but this can decrease the resource base available for pollinators. We developed a simulation model to examine the consequences of such asynchrony for individual reproductive success and long-term pollinator maintenance with- in monoecious fig populations. In figs, flowering is synchronous within a tree and the specialist pollinators/seed predators can only survive briefly away from trees. Consequently, population-level flowering asynchrony must extend year-round for pollinators to persist locally. In repeated stochastic simulations using phenological traits of one well-studied species (Ficus natalensis), a median of 95 trees was required to produce an asynchronous sequence that could maintain local pollinator populations for 4 yr. However, many trees in those simulated populations were either male-sterile (10%) or both male- and female- sterile (35%), because their sexual phases were not well timed with the opposite phases of other trees. Sterility within a population approached zero at 2-3 times the critical population size. Both the predicted critical population size and frequency of success of the trees within it depended strongly on the duration of reproductive episodes and the intervals between episodes. The level of within-tree reproductive synchrony was also critical: doubling the length of time over which individuals could donate pollen resulted in a 39% decrease in critical population size and a 27% increased likelihood that individuals would achieve at least some reproductive success. These results point to the need for precise phenological data for estimating plant fitness and population structure both in models and in the field.

Cathepsin D: a protease involved in breast cancer metastasis

Abstract: Cathepsin D is an acidic lysosomal protease present in all cells. In estrogen receptor positive and negative breast cancer cell lines, the mRNA coding for pro-cathepsin D is overexpressed and sorting and maturation of the pro-enzyme are altered, via possibly saturation of the Man-6-P/IGF-II receptor, leading to accumulation of the active proteinase in large endosomes and to secretion of the precursor (52K protein). In MCF7 cells, the cathepsin D mRNA is induced directly and transcriptionally by estrogens and indirectly by growth factors. In patients, there is a significant correlation between high cathepsin D concentrations in the cytosol of primary breast cancer and development of metastasis. This marker is independent of other prognostic factors and appears to be particularly useful in axillary node-negative tumors. Transfection of a human cDNA cathepsin D expression vector under the control of SV40 promoter increases the metastatic potential of 3YA1-Ad12 rat tumorigenic cells when intravenously injected into nude mice. The mechanism of cathepsin D-induced metastasis is currently unknown. These results indicate that overexpression of cathepsin D might facilitate breast cancer metastasis, suggesting new possible therapeutic approaches.

Glasses from aerogels

Abstract: Silica glasses are obtained by the densification of aerogels. The transformation of the material into a glass is followed by differential thermal analyis, thermo-gravimetric analysis, dilatometry and by the evolution of the structural, textural and mechanical properties of the material. The organic species and the hydroxyl groups are removed by oxidation and chlorination heat treatments in such a way as to avoid bloating and crystallization phenomena during sintering. Densification is obtained by heat treatment at a low temperature (1100 to 1300 ° C). The densified aerogel shows physical properties identical to those of molten silica. Moreover, this material is very pure and its water content is low. The same process can be extrapolated to multicomponent glasses and composite materials.

Cathepsin D in breast cancer.

Abstract: Cathepsin D is an acidic lysosomal protease present in all cells. In estrogen receptor positive and negative breast cancer cell lines, the mRNA coding for pro-cathepsin D is overexpressed and sorting and maturation of the pro-enzyme are altered, leading to accumulation of the active proteinase in large endosomes and to secretion of the precursor (52K protein). In MCF7 cells, the cathepsin D mRNA is induced directly and transcriptionally by estrogens and indirectly by growth factors. In vitro, pro-cathepsin D is an autocrine mitogen on breast cancer cells and can be auto-activated to degrade extracellular matrix and proteoglycans and to activate other proteinases in acidic microenvironments. In patients, there is a significant correlation between high cathepsin D concentrations in the cytosol of primary breast cancer and development of metastasis. This marker is independent of other prognostic factors and appears to be particularly useful in lymph node-negative tumors. These results suggest that overexpression and possible derouting of cathepsin D plays an important role in invasion and metastasis of breast cancer.

Definition of the human immunoglobulin variable lambda (IGLV) gene subgroups

Abstract: Comparison of 60 human immunoglobulin variable lambda (IGLV) sequences allowed us to define seven subgroups designated V lambda I to V lambda VII. We demonstrate that all lambda proteins sequenced so far fall into the subgroups I, II, III and VI, and that the lambda regions previously assigned to subgroups IV and V belong, in fact, to subgroups III and II, respectively. Four sequences not belonging to any of the subgroups I, II, III and VI define the new subgroups IV, V and VII. Interestingly, these subgroups show a higher homology to rabbit or mouse V lambda genes than to the other human V lambda subgroups. By comparison of the proteins either with the sequences deduced from the germ-line genes or with the consensus sequences, the rate of amino acid changes due to somatic mutations or allelic variations was evaluated in several lambda proteins. Framework and complementarity-determining regions of the human IGLV genes and proteins were delineated. Alignment of the lambda sequences shows that functional V-J rearrangement occurs, with or without deletion of nucleotides encoding one or two amino acids at the 3' end of the V gene. Diversity of the third complementarity-determining region is due to somatic mutations and to flexible V-J junction, but there is no evidence of N-diversity in the human lambda locus.

Effect of aging and pH on the modulus of aerogels

Abstract: The elastic modulus E of an aerogel is related to its density ϱ by E = c(pH)ϱ3.7 for gels made at various pH values; however, the constant of proportionality c depends on pH. It is found that this relation applies regardless of whether the density is varied by lengthy aging or by increasing the concentration of tetramethoxysilane (TMOS) in the initial sol; that is, changes in aging time and [TMOS] evidently have equivalent effects on gel structure. The influence of pH on densification can be understood in terms of competition between polycondensation (P, which produces shrinkage) and dissolution/ reprecipitation (D/R, which increases the rigidity of the network). At low pH, P dominates, but at high pH D/R stiffens the network and inhibits shrinkage.

Sol-gel preparation and transport properties of a tin oxide

Abstract: Much work has already been carried out concerning the preparation and study of tin (IV) oxide, alone and combined with other oxides, for applications related to electrical and catalytic properties. The methods of preparation have included: (i) coprecipitation of hydroxides or oxalates starting from diluted salts; (ii) solid state reactions, by decomposition of carbonates, hydroxides; (iii) deposits by vapour phase deposition; and (iv) oxidation of SnO (e) in SnO2 by epitaxial growth. It has been noticed that the properties related to this oxide depend on the texture of the material. For this reason the sol-gel procedure was used to prepare such a compound. Generally the gel is formed by peptisation (with nitric acid) of Sn(OH)4 obtained after action on tin chloride by ammonia [1-3]. The study of these ge][s has shown that there is a temperature dependent structural evolution [3, 4] with oxygen deficient oxide [5]. Within this scope we have prepared a pure gel using a new method, the hydrolysis of a tin (II) alkoxide, and compared its structure to other gels. We have studied this gel by the method of complex permittivities. In fact, for a long time, dielectric loss measurements have been the basis of various investigations on many chalcogenides and a few oxides [6, 7]. The results obtained have usually been interpreted by theoretical models using the concept of charge carriers hopping between localised sites. Experimental data of the a.c. conduction as a function of frequency have often exhibited the following behaviour [6-10]: % = + (1) where Odc is the conductivity in direct current; o-' (co), the real part of the polarisation conductivity, is related to the frequency, f, by the expression: cr'(co) = Ac0' (co = 2zcf) where A and s are constants at a given temperature. In this work the a.c. conductivity, as a function of frequency and temperature of the oxide was measured. The a.c. conductivity data were analysed using a numerical approach described previously [11]. The results showed that the a.c. behaviour of this poorly organised tin oxide could be described by a well-known theoretical model related to thermally activated electron hopping. The method used for the synthesis of the tin alkoxide

Esterases A2 and B2 in Culex quinquefasciatus (Diptera: Culicidae): role in organophosphate resistance and linkage.

Abstract: Two highly active esterases, A2 and B2, were isolated in SeLax, a strain of Culex quinquefasciatus Say from California which demonstrated resistance levels of 19, 14, and 4.3 times to the organophosphate insecticides chlorpyrifos, temephos, and malathion, respectively. Selection of SeLax by temephos during 31 generations increased resistance to this insecticide to 65 times. This resistance was shown to be DEF-suppressible, monofactorial, and strongly associated with the presence of esterases A2 and B2. Although these two esterases are encoded by distinct structural genes, no disjunction was observed when SeLax was crossed to S-Lab, a susceptible strain, or to S54, a strain resistant to organophosphates by means of esterase A1. However, when SeLax was crossed to strain Tem-R, which is resistant to organophosphates because of a highly active esterase B1, all possible recombinants occurred. These results were discussed in relation to the recent discovery that increased activity of B esterases in the genus Culex is caused by gene amplification.

Cathepsin D in breast cancer: from molecular and cellular biology to clinical applications.

Abstract: Cathepsin D is a ubiquitously expressed lysosomal protease. Initially synthesized as an inactive precursor of 52 kD (pro-cathepsin D), the enzyme is subsequently converted to its active forms by proteolytic processing. Breast cancer cells, unlike normal cells, secrete high levels of pro-cathepsin D; this abnormal secretion is due to both overexpression of the gene and altered processing of the protein. Recent transfection experiments indicate that overexpression of cathepsin D can increase the metastatic potential of tumor cells in nude mice. This study complements clinical studies, which have shown than high cathepsin D concentrations in the cytosol of primary breast cancers may be predictive of subsequent metastasis, particularly for patients with axillary node-negative tumors. These results, and the potential mechanisms by which cathepsin D may promote metastasis, are considered here.

Inbreeding depression and self-fertilization in Lymnaea peregra (Gastropoda: Pulmonata)

Abstract: The effects of self-fertilization and cross-fertilization on several fitness traits were examined in the freshwater hermaphrodite snail Lymnaea peregra. Laboratory strains were established from Lake Geneva populations. Comparisons of F2 snails and their offspring showed that there are no differences in hatching time, nor in the size of young snails monitored over one month. But there was a significant difference, when the distribution of the capsule weight against the number of eggs was compared, although the effects of this on fitness are probably small. There was also a significant difference for egg production and juvenile viability over one month; the selfing snails are 94 per cent less fit for these two traits than the outcrossing.

Input waveform slope effects in CMOS delays

Abstract: Slow input ramp effects in delay evaluation on CMOS structures are considered. Corrections of previously defined closed-form equations are proposed, allowing accurate evaluation of delays in a large range of configurations. The expressions obtained remain sufficiently manageable to be used in an automatic data-path sizing tool. >

Comparison of terrestrial and marine temperature estimates for the past 135 kyr off southeast Africa: a test for GCM simulations of palaeoclimate

Abstract: A combined oxygen isotope, planktonic foraminiferal and pollen record from the southwestern Indian Ocean makes possible a comparison between estimated lowland terrestrial temperatures and isotope and faunal sea surface temperatures. The estimates of land and sea mean temperatures over the past 135 kyr are consistent to within 0.5 °C, and in all three records the maximum temperature changes between glacial and interglacial times are about 3–4 °C.

Immunoelectron microscopic localization of neurotransmitters in the cochlea.

Abstract: This paper presents the works and methods of our respective laboratories using electron microscopic immunocytochemistry to identify and localize cochlear neurotransmitters. Antibodies to various prospective neurotransmitters and associated enzymes have been used to study the ultrastructural localization of several candidates for olivocochlear efferent neurotransmitters previously suggested by light microscopic immunocytochemistry. Antibodies against enkephalins label lateral olivocochlear efferent fibers. Antibodies against choline acetyltransferase (ChAT) (an enzyme marker for acetylcholine) label a major population of both lateral and medial efferent fibers and terminals, whereas antibodies to gamma-aminobutyric acid (GABA) label what might be a small subpopulation of both the lateral and medial efferent systems. The GABA-like immunostained medial efferent fibers are preferentially located in the upper turns of the guinea pig cochlea, particularly the third turn. Immunoelectron microscopy shows that neither GABA nor ChAT immunolabels all medial efferent terminals, regardless of cochlear turn. All the different types of immunolabeled efferent terminals have been observed to make characteristic synaptic contacts; lateral efferent terminals on afferent dendrites and medial efferent terminals on outer hair cells and occasionally on type II afferent dendrites. Other types of contacts involving GABA-like, and sometimes met-enkephalin-like, immunostained fibers are occasionally seen particularly in the upper turns of the cochlea. Immunoelectron microscopic results suggest that both medial and lateral efferent systems might be further subdivided on the basis of differences in neurotransmitters. Future trends of immunocytochemical research on cochlear neurotransmitters are proposed, particularly colocalization studies, which show a complex pattern of coexistence of neurotransmitters in the lateral efferent system.

Morphometric stepwise discriminant analysis of the five genetically determined European taxa of the genus Mus

Abstract: U nivariate and multivariate analyses have been performed on skull and mandible measurements for the five biochemically defined groups of the genus Mus in Europe. Four of these taxa occur in Bulgaria; other sam pIes came from France and Israel. This extensive biometrical analysis bas allowed us to establish diagnostic keys for these taxa.

Prevention of Clostridium difficile-induced experimental pseudomembranous colitis by Saccharomyces boulardii: a scanning electron microscopic and microbiological study

Abstract: Summary: The ability of Saccharomyces boulardii to protect mice against intestinal pathology caused by toxinogenic Clostridium difficile was studied. Different regions of the intestine of experimental mice were prepared for observation by scanning electron microscopy or homogenized for C. difficile enumeration and quantification of toxin A by enzyme immunoassay and toxin B by cytotoxicity. The test group was treated for 6 d with an S. boulardii suspension in drinking water and challenged with C. difficile on day 4. The three control groups were: axenic mice, mice treated with only S. boulardii and mice only challenged with C. difficile. The results showed that: (i) 70% of the mice infected by C. difficile survived when treated with S. boulardii; (ii) the C. difficile-induced lesions on the small and large intestinal mucosa were absent or markedly less severe in S. boulardii-treated mice; and (iii) there was no decrease in the number of C. difficile but rather a reduction in the amount of toxins A and B in S. boulardii-treated mice.

Structural aspects of sol-gel synthesis

Abstract: The various methods for studying the structure of the gel backbone and the texture of gels are reviewed. The difficulties of applying the fractal concepts are critically presented and a non-fractal aggregation model with a variable coordination index proposed.

Synthesis of poly(alkynylsilanes) having various aromatic groups in the backbone

Abstract: Preparation des polymeres [-C:C-SiR 2 -C:C-Ar-] n (R= Ph, Ar= Ph, Ph-Ph, C 14 H 8 , C 13 H 8 ,NC 5 H 3 ,NC 5 H 3 -NC 5 H 3 , SC 4 H 2 ) par polycondensation catalytique du diethynyldiphenylsilane avec les dihalogenures aromatiques correspondants. Caracterisation par RMN 13 C et 29 Si.

Action des glycosidases exogènes au cours de la vinification : libération de l'arôme a partir de précurseurs glycosidiques

Abstract: L'action des glycosidases exogenes d'origine fongique (α-arabinosidase, α-rhamnosidase, β-apiosidase, β-glucosidase) a ete etudiee en vinification en vin doux naturel (VDN) et en vin sec du mout de Muscat de Frontignan. La teneur en fraction libre de l'arome a montre une forte augmentation dans le cas du vin sec issu du mout enzyme : d'une part la concentration en certains terpenols (nerol, geraniol, citronellol, α-terpineol, hydroxylinalols) a sensiblement augmente, d'autre part des composes nor-isoprenoidiques (β-damascenone, 3- hydroxy-β-damascone), interessants sur le plan olfactif, ont apparu. On a demontre que l'augmentation de la concentration de la plupart des composes aromatiques etait le resultat de l'action hydrolytique des glycosidases exogenes sur les precurseurs glycosidiques. Le vin sec issu du mout enzyme a ete juge plus aromatique (floral) et plus type. Dans le cas du VDN issu du mout enzyme, l'hydrolyse des precurseurs glycosidiques d'arome a ete interrompue au stade de monoglucosides, du a l'inhibition de l'activite β-glucosidase par la presence du glucose. Ainsi la fraction libre de l'arome n'a pu augmenter comme dans le cas du vin sec enzyme.

Auditory hair cells in human fetuses: synaptogenesis and ciliogenesis.

Abstract: This paper brings together the most recent findings concerning the development of human fetus cochlear hair cells, as observed using transmission and scanning electron microscopy (TEM and SEM). Specific attention is drawn to the formation of synapses and the growth of stereocilia. In both types of hair cells, synaptogenesis begins before ciliogenesis (week 10 of gestation versus week 12). In the inner hair cell (IHC), an adultlike stage is seen around week 15 for synapses, but not before week 22 for stereocilia. In the outer hair cell (OHC), both synapses and stereocilia are not yet fully mature at week 22. Classic gradients of maturation are found: a base-to-apex gradient, and an IHC-to-OHC gradient. By comparing these results with the anatomical and functional data on cochlear development in laboratory mammals, the onset of cochlear function in the human fetus can be estimated to occur around week 18. The completion of cochlear maturation based upon the same anatomical criteria should occur about 10 weeks later.