Showing papers by "University of Nice Sophia Antipolis published in 1994"
TL;DR: The authors have adopted a new nomenclature for the laminins, in which the previous A, B1 and B2 chains, and their isoforms, are alpha, beta and gamma, followed by an arabic numeral to identify the isoform.
743 citations
TL;DR: In this paper, the multichannel version of the singular spectrum analysis (M-SSA) is developed and applied to an NMC 32-year long set of 700-hPa geopotential heights.
Abstract: The low-frequency variability in the midlatitudes is described through an analysis of the oscillatory phenomena. In order to isolate nearly periodic components of the atmospheric flow, the multichannel version of the singular spectrum analysis (M-SSA) is developed and applied to an NMC 32-year long set of 700-hPa geopotential heights. In the same way that principal component analysis identifies the spatial patterns dominating the variability, M-SSA identifies dynamically relevant space–time patterns and provides an adaptive filtering technique. Three major low-frequency oscillations (LFOs) are found, with periods of 70 days, 40–45 days, and 30–35 days. The 70-day oscillation consists of fluctuations in both position and amplitude of the Atlantic jet, with a poleward-propagating anomaly pattern. The 40–45-day oscillation is specific to the Pacific sector and has a pronounced Pacific/North American (PNA) structure in its high-amplitude phase. The 30–35-day mode is confined over the Atlantic region,...
403 citations
357 citations
TL;DR: The increased Na+ reabsorption that occurs at birth as a necessary event to pass to an air-breathing environment is probably associated with control of transcription of this Na+ channel, which is highly selective for Na+.
Abstract: Water balance in the lung is controlled via active Na+ and Cl- transport. Electrophysiological measurements on lung epithelial cells demonstrated the presence of a Na+ channel that is inhibited by amiloride (K0.5 = 90 nM) and some of its derivatives such as phenamil (K0.5 = 19 nM) and benzamil (K0.5 = 14 nM) but not by ethylisopropylamiloride. An amiloride-sensitive Na+ channel of 4 pS was recorded from outside-out patches excised from the apical membrane. This channel is highly selective for Na+ (PNa+/PK+ > or = to 10). Isolation of a human lung cDNA led to the primary structure of the lung Na+ channel. The corresponding protein is 669 residues long and has two large hydrophobic domains. An amiloride-sensitive Na(+)-selective current apparently identical to the one observed in lung epithelial cells was recorded after expression of the cloned channel in oocytes. The level of the mRNA for the Na+ channel was highly increased from fetal to newborn and adult stages. This observation indicates that the increased Na+ reabsorption that occurs at birth as a necessary event to pass to an air-breathing environment is probably associated with control of transcription of this Na+ channel. The human gene for the lung Na+ channel was mapped on chromosome 12p13.
232 citations
Journal Article•
TL;DR: It is concluded that the downstream elements of the growth factor signalling cascade, MAPKK-MAPK, are both necessary and sufficient to promote growth factor signals and autonomous cell cycling in fibroblasts.
Abstract: The Mitogen Activated Protein Kinase (MAPK) module operates downstream of Ras to convey cell surface signals to the nucleus via the nuclear translocation of p42/p44 MAPKs We have previously established that MAPK activation is obligatory and must persist in the G1 phase to allow resting fibroblasts to exit from G0 (Pages et al, Proc Natl Acad Sci1993, 90, 8319-8323) It remained to be established whether MAPK activation was sufficient to trigger cell proliferation To this aim, we generated and expressed in Chinese hamster lung fibroblasts, constitutively active mutants of hamster MAP kinase kinase (MAPKK) Three mutants: S218D, S222D and S218D/S222D in which we substituted the Raf1/MAPKKK-dependent regulatory phosphorylation sites by aspartic acid residues, displayed increased basal activity when expressed in fibroblasts Two of them, S218D and S218D/S222D which have a basal activity higher than serum-stimulated wild type-MAPKK (respectively 2- and 5-fold), induced activation of p42 MAPK in growth factor-deprived cells Interestingly, only these two mutants led to a growth factor-independent state as judged by early gene transcription (activation of the fos promoter), increased sensitivity to growth factors for reinitiation of DNA synthesis, autonomous cell cycling and rapid tumor formation in nude mice Therefore we conclude that the downstream elements of the growth factor signalling cascade, MAPKK-MAPK, are both necessary and sufficient to promote growth factor signals and autonomous cell cycling in fibroblasts
230 citations
TL;DR: In this paper, a phenomenological model based on the minimization of the free energy is proposed and reported in detail, which represents a significant improvement compared to previous theoretical approaches related to well-known thermodynamic size effect models, particularly insofar as the agreement with the experimental results is concerned.
217 citations
TL;DR: Results support Ang II as being able, by means of binding to a receptor of the AT2 subtype present in adipose cells, to control the adipogenic effect of PGI2 through a paracrine mode of action.
Abstract: Prostacyclin (PGI2), the major metabolite of arachidonic acid in adipose tissue, has been shown to play a key role in the process of preadipose cell differentiation in vitro. Moreover, angiotensin-II (Ang II) is able to induce the production of PGI2 in suspensions of isolated adipocytes as well as in the interstitial fluid of rat adipose tissue. A possible role of Ang II in the control of the autocrine-paracrine adipogenic effect of PGI2 has been investigated, using cells of the Ob1771 preadipocyte clonal line cultured in serum-free chemically defined medium. Whereas both preadipose and adipose cells were able to produce PGI2 upon exposure to arachidonic acid, only adipose cells were able to do so when challenged with Ang II. In agreement with this observation, the ability of Ang II to induce preadipose cells to differentiate required the simultaneous presence of differentiated cells. Such coculture experiments show that the promoting effect of Ang II on preadipose cell differentiation was strongly reduce...
212 citations
TL;DR: This work proposes a new solution to the problem of determining the shortest paths of bounded curvature joining two oriented points in the plane based on the minimum principle of Pontryagin.
Abstract: Given two oriented points in the plane, we determine and compute the shortest paths of bounded curvature joining them. This problem has been solved recently by Dubins in the no-cusp case, and by Reeds and Shepp otherwise. We propose a new solution based on the minimum principle of Pontryagin. Our approach simplifies the proofs and makes clear the global or local nature of the results.
209 citations
TL;DR: A potential link observed in vivo between an increase in fatty acid supply induced by high-fat or high-carbohydrate diets and the hyperplastic development of adipose tissue is provided.
197 citations
TL;DR: In this article, the authors present experimental evidence showing the ubiquitous presence in the lower atmosphere (at least up to 25 km) of very strong (positive) temperature gradients within very thin layers.
Abstract: This paper presents experimental evidence showing the ubiquitous presence in the lower atmosphere (at least up to 25 km) of very strong (positive) temperature gradients within very thin layers. The presence of such “sheets” in the temperature field of the free atmosphere was frequently hypothesized in order to account for the aspect sensitivity of VHF radar measurements. Owing to their high vertical resolution (20 cm) and to the fast-response thermometers used, the in situ balloon measurements discussed in this paper constitute the first direct evidence of their true existence. Statistical study of the properties of the sheets results in the following typical values: thickness 3–20 m, temperature increase 0.2–0.8 K, gradient 30–100 K/km. The sheets are frequently observed in groups, associated with and taking part in regions of high static stability. Local measurements using two pairs of sensors one meter apart indicate that the sheets are not flat and horizontal. Sometimes, clear evidence of ong...
196 citations
TL;DR: In this article, the authors considered the problem of price risk in the presence of an uncertain "random" market and proposed a simple and powerful formalism which allows them to generalize the analysis to a large class of stochastic processes, such as ARCH, jump or Levy processes.
Abstract: The ability to price risks and devise optimal investment strategies in the presence of an uncertain "random" market is the cornerstone of modern finance theory. We first consider the simplest such problem of a so-called "European call option" initially solved by Black and Scholes using Ito stochastic calculus for markets modelled by a log-Brownien stochastic process. A simple and powerful formalism is presented which allows us to generalize the analysis to a large class of stochastic processes, such as ARCH, jump or Levy processes. We also address the case of correlated Gaussian processes, which is shown to be a good description of three different market indices (MATIF, CAC40, FTSE100). Our main result is the introduction of the concept of an optimal strategy in the sense of (functional) minimization of the risk with respect to the portfolio. If the risk may be made to vanish for particular continuous uncorrelated 'quasiGaussian' stochastic processes (including Black and Scholes model), this is no longer the case for more general stochastic processes. The value of the residual risk is obtained and suggests the concept of risk-corrected option prices. In the presence of very large deviations such as in Levy processes, new criteria for rational fixing of the option prices are discussed. We also apply our method to other types of options, `Asian', `American', and discuss new possibilities (`doubledecker'...). The inclusion of transaction costs leads to the appearance of a natural characteristic trading time scale.
Journal Article•
TL;DR: A working model of MCH regulation/function in mammalian brain is proposed and Chromosomal assignment of the authentic and variant MCH genes in rat and human indicates that these genes may be good candidates involved in neurodegenerative or psychiatric disorders.
Abstract: Melanin-concentrating hormone (MCH) is a cyclic peptide originally isolated from chum salmon pituitaries, then structurally characterized from rat hypothalami. In the fish, MCH induces melanin concentration within the melanophores and may inhibit ACTH secretion in vitro and under stressful conditions in vivo. In the rat, MCH modulates ACTH release in vivo and oxytocin secretion in vitro. However, on the basis of neuroanatomical features, that is, cell bodies almost exclusively confined to the lateral area of the hypothalamus and the zona incerta, while fibers are observed throughout whole rat or human brains, this peptide appears to participate as a neurotransmitter/neuromodulator in the control of goal-oriented behaviors and/or general arousal in mammals. The knowledge of structural and regulatory features of the MCH precursor, mRNA, and genes at the cellular and molecular levels has recently made great progress. (1) The cells expressing MCH and associated peptides have been defined conjointly using radioimmunoassay, immunocytochemistry, and in vitro and in vivo molecular hybridization techniques. (2) The organization of the precursor deduced from cDNA cloning has been established and led to the discovery of two novel putative peptides named NEI and NGE. (3) The regulation of MCH mRNA and peptide production has been explored during the course of development in rodent and human and under a variety of paradigms (neurogenic or osmotic stress, hormonal stimuli, etc.). (4) The structure of the MCH genes has been determined in salmon, rat, mouse, and human and revealed striking exon-intron organization differences between fish and mammals. Strong homology, with a likely functional implication, was found between salmon MCH mRNA and 7SL RNA, a structural RNA involved in protein translocation. Furthermore, a variant gene that may encode slightly different MCH was found exclusively in primates. (5) Chromosomal assignment of the authentic and variant MCH genes in rat and human indicates that these genes may be good candidates involved in neurodegenerative or psychiatric disorders. Based on the framework of these studies, a working model of MCH regulation/function in mammalian brain is finally proposed.
Journal Article•
TL;DR: It is reported that a new thiazolidinedione compound, BRL 49653, exerts potent effects on the expression of genes encoding proteins involved in fatty acid metabolism in preadipose cells, similar to those already described for natural or nonmetabolizable fatty acids.
Abstract: In diabetic rodents, thiazolidinediones are able to improve insulin sensitivity of target tissues and to reverse, at least partially, the diabetic state. The effects of these drugs on phenotypic expression in various tissues, including adipose tissue, have been reported. We report here that a new thiazolidinedione compound, BRL 49653, exerts, in preadipose cells, potent effects on the expression of genes encoding proteins involved in fatty acid metabolism. These effects of BRL 49653 in Ob 1771 preadipose cells are similar, in terms of kinetics, reversibility, specificity of genes affected, and requirement for protein synthesis, to those already described for natural or nonmetabolizable fatty acids. Moreover, when used at submaximally effective concentrations, BRL49653 and 2-bromopalmitate act in an additive manner to induce gene expression in preadipose cells, but this additivity of effects is lost when one of the compounds is used at a maximally effective concentration. These observations, suggesting similar mechanisms of action for thiazolidinediones and fatty acids, are strongly supported by the demonstration that (i) both molecules activate, in a heterogolous trans-activation assay, the same nuclear receptor of the steroid/thyroid hormone nuclear receptor superfamily and (ii) transfection of 3T3-C2 fibroblasts with an expression vector for this nuclear receptor confers thiazolidinedione inducibility of adipocyte lipid-binding protein gene expression.
TL;DR: In this paper, conjunctival inflammatory antigens were investigated in impression cytology specimens from patients who have been and those who have not been treated for glaucoma.
TL;DR: Results strongly suggest that Ser222 represents one key MAPKKK‐dependent phosphorylation site switching on and off the activity of MAPKK, an event crucial for growth control.
Abstract: In response to various external stimuli, MAP kinases are activated by phosphorylation on tyrosine and threonine by MAP kinase kinase (MAPKK), a dual specificity kinase. This kinase is in turn activated via Raf-1 and MAPKK kinase (MAPKKK). To determine regulatory phosphorylation sites of MAPKK, we isolated a Chinese hamster cDNA, that we epitope-tagged and expressed in fibroblasts. This hamster MAPKK (MEK1 isoform) can reactivate recombinant p44mapk when immunoprecipitated from growth factor-stimulated cells or when incubated with an active form of MAPKKK. Mutations at either of two residues that are conserved among kinases, D208N or S222A, abolished MAPKK activity. However, only S222A/MAPKK showed a reduction in phosphorylation in response to active MAPKKK and exerted a dominant negative effect on the serum-stimulated endogenous MAPKK. Finally, replacing Ser222 with Asp, a negatively charged residue, restored MAPKK activity independently of the upstream kinase. These results strongly suggest that Ser222 represents one key MAPKKK-dependent phosphorylation site switching on and off the activity of MAPKK, an event crucial for growth control.
TL;DR: To determine unambiguously the sites of glycosylation and their role in biosynthesis and cation transport, site-directed mutagenesis at the individual potential N-glycosidase sites (Asn to Asp) was performed and all possible double and triple mutants were constructed.
Abstract: The ubiquitously-expressed human Na+H+ exchanger (NHE-1) contains three consensus sites (Asn-X-Ser/Thr) for N-linked glycosylation at asparagines 75, 370, and 410. The first extracellular loop is rich in serine and threonine residues which may contain O-linked carbohydrate. In order to determine unambiguously the sites of glycosylation and their role in biosynthesis and cation transport, site-directed mutagenesis at the individual potential N-glycosylation sites (Asn to Asp) was performed and all possible double and triple mutants were constructed. The mutated DNAs were expressed in PS120 hamster fibroblasts lacking endogenous exchanger, and the transfected cells were selected by their ability to survive acute intracellular acidification. All constructs produced functional exchangers that had transport rates and pharmacological profiles that were similar to that of wild-type. Immunoblot analysis of the expressed proteins with and without N-glycosidase F treatment showed that only the first N-glycosylation site (Asn 75) is utilized. In addition, treatment of NHE-1 with neuraminidase and O-glycosidase demonstrated that NHE-1 also contains O-linked oligosaccharide. Two forms of NHE-1 was consistently observed, a mature form with a molecular mass of 110,000 Da which contains N-linked and O-linked oligosaccharide and is expressed at the cell surface, and a lower molecular mass form (85,000 Da) present in the endoplasmic reticulum which only contains N-linked high-mannose oligosaccharide. NHE-3, an apically-expressed epithelial isoform which does not possess the N75 N-linked putative glycosylation site and any extracellular loops enriched in serine and threonine residues, does not exhibit any detectable glycosylation.
TL;DR: It is shown that, when present at concentrations below or close to the Kd values of retinoic acid receptors, retinoids behave as potent adipogenic hormones (1 pM to 10 nM range) and, by the use of specific ligands for each RAR subtype, these positive effects on adipose differentiation involve in particular the RAR alpha subtype.
TL;DR: It is noteworthy that nicein/kalinin subunits share discrete sequence similarities with the B2 chain of human laminin, but with a cleavage occurring within domain III that eliminates domains IV and V from the final product.
Abstract: We have isolated the basement membrane component nicein and performed rotary-shadow analyses using electron microscopy that showed the presence of two forms (I and II) of the protein. Molecular cloning of the cDNA that codes for the 100-kDa chain of the protein revealed that the sequence matches those independently identified for the 105–155-kDa subunit of kalinin, a recently identified basement membrane component. These data demonstrate that nicein and kalinin contain an identical chain. The length of the open reading frame in the cDNA (∼5200 nucleotides) and amino acid sequences obtained from the N-terminus of the 105-kDa kalinin chain showed the occurrence of a precursor polypeptide. This immature polypeptide is probably related to form I, observed by rotary shadowing, while the mature form is related to form II. It is noteworthy that nicein/kalinin subunits share-discrete sequence similarities with the B2 chain of human laminin, but with a cleavage occurring within domain III that eliminates domains IV and V from the final product. The sequence of this subunit is nearly identical to that of B2t, a recently described polypeptide supposed to be related to a new laminin variant. Since nicein/kalinin expression is specifically impaired in the severe genodermatosis Herlitz junctional epidermolysis bullosa, the role and structure of this tissue-restricted laminin variant is crucial for the understanding of epidermal-dermal adhesion.
TL;DR: The Guerrero terrane, composed of Late Jurassic-Early Cretaceous sequences, extends from Baja California to Acapulco and is considered to be coeval with the late Mesozoic igneous and sedimentary arc sequences of the Greater Antilles, the West Indies, Venezuela and the Western Cordillera of Colombia as discussed by the authors.
TL;DR: It is shown that, in contrast to its antagonistic action on NT‐ induced hypomotility in the rat, SR 48692 failed to antagonize NT‐induced hypothermia and analgesia in the mouse and rat, and it is suggested that these effects might be mediated through a subtype ofSR 48692‐insensitive NT receptor.
Abstract: The nonpeptide neurotensin (NT) antagonist, SR 48692, was recently shown to inhibit NT binding to the cloned rat and human NT receptor and to antagonize NT effects in a variety of in vitro and in vivo assays. Here, we show that, in contrast to its antagonistic action on NT-induced hypomotility in the rat, SR 48692 failed to antagonize NT-induced hypothermia and analgesia in the mouse and rat. We suggest that these effects might be mediated through a subtype of SR 48692-insensitive NT receptor.
TL;DR: The stability (with respect to encapsulated carboxyfluorescein release) of fluorinated liposomes and their membrane permeability have been investigated in buffer and in human serum as compared to conventional hydrogenated analogues, and 'Gel' or 'gel-like' fluorinatedliposomes are significantly more stable in serum than in buffer.
TL;DR: In this article, the basic physical and chemical characteristics of fluorocarbons and fluorinated materials (especially surfactants), in neat or dispersed form (emulsions, vesicles), which determine their potential in medicine are summarized.
TL;DR: It is demonstrated, by site directed mutagenesis, that MAPK is able to retrophosphorylate its own activator, MAPKK, on two threonine residues Thr‐292 and Thr‐386 in vitro, and that these sites are also phosphorylated in vivo.
TL;DR: The stoichiometric binding model predicts that functional receptors also act as clearance receptors and provides an explanation for the observation that antagonists of endothelin receptors are also clearance antagonists.
Abstract: Physiological and pathophysiological roles of endothelins are still unclear. One reason is that circulating endothelin levels in normal and pathological states are much lower than the concentrations necessary to elicit contractions in vitro. It is usually assumed that endothelin accumulates in diseased tissues and that, because of its degradation, only a small fraction of it reaches the systemic circulation. Such a hypothesis does not fit with recent observations showing that low circulating endothelin levels may be active. We show here that most of the current inferences about the actions of endothelin assume that the peptide acts in the vessel wall under conditions known as non-stoichiometric binding conditions, that is, under conditions in which the receptor concentration in tissues ([Ro]) is smaller than the equilibrium dissociation constant of endothelin receptor complexes (Kd). Under stoichiometric binding conditions (defined by the condition [Ro] > Kd), most ligand molecules are bound to receptors and cannot be present in a free form. Estimates of [Ro] and Kd from the literature suggests that in vivo endothelin probably binds stoichiometrically to its receptors. Under this condition, most of tissue endothelin is probably bound to receptors. It is therefore suggested that plasma endothelin levels are low probably because tissue free endothelin levels are low, and this is not inconsistent with the presence of high tissue levels of active (that is, bound) endothelin. When the topology of the vessels with respect to the site of production (or of delivery) of endothelin is considered, stoichiometric binding may also account for the higher sensitivity to Et-1 of in vivo preparations. It also suggests that autocrine and paracrine actions of Et-1 are favoured at low and high secretory rates respectively, thus providing an explanation for the dual (vasodilator and vasoconstricting) actions of endothelin. Finally, the stoichiometric binding model predicts that functional receptors also act as clearance receptors and provides an explanation for the observation that antagonists of endothelin receptors are also clearance antagonists.
TL;DR: In this article, a variety of oxo or non-oxo mixed-metal acetatoalkoxides have been characterized in the solid (X-ray on single crystals) as well as in solution (FT-IR, multinuclear NMR).
TL;DR: The results emphasize the adipogenic, nonmitogenic role of cPGl2 and also allow the distinction between the various adipogenic/mitogenic factors which affect adipose cell differentiation.
Abstract: Primary rat adipose precursor cells, maintained in the minimal chemically defined medium (ITT medium) able to promote differentiation, have been used to investigate the ability of several agents to modulate their proliferation and their differentiation. Fetuin and fibroblast growth factor (FGF), which exhibited a strong and a weak mitogenic activity, respectively, do not significantly affect the proportion of differentiated cells as indicated by glycerol-3-phosphate dehydrogenase (GPDH) activity values. In contrast, carbaprostacyclin (cPGI2), a stable analogue of prostacyclin, behaves as a true adipogenic factor leading to a 4 to 5-fold increase in GPDH-specific activities with no significant effect on cell growth. Submaxillary gland kallikrein (SMGK), transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) behave as growth-promoting agents but at the same time elicit a dose-dependent inhibition of differentiation. Epidermal growth factor (EGF) and prostaglandin F2 alpha (PGF2 alpha) do not show any effect on cell proliferation at concentrations which exert a maximal inhibitory action on differentiation. Upon removal of EGF from the culture medium, complete resumption of differentiation occurs, whereas upon removal of PGF2 alpha or SMGK, complete resumption only takes place when differentiation is triggered by cPGI2. Upon removal of TNF-alpha, a partial resumption of differentiation is observed, whereas no subsequent differentiation is observed upon TGF-beta removal. These results emphasize the adipogenic, nonmitogenic role of cPGI2 and also allow the distinction between the various adipogenic/mitogenic factors which affect adipose cell differentiation.
TL;DR: In this article, the superbase gas phase scale was further extended up to proton affinities of ca 1080 kJ mol−1 by use of cyclic and acyclic guanidines and vinamidines.
TL;DR: Fifty unselected subjects living in Alpes-Maritimes, France, a high risk area for visceral leishmaniasis due to Leishmania infantum, were examined simultaneously by the leish manin skin test and the Western blot technique in 1993; 32% and 38%, respectively, gave a positive reaction.
Abstract: Fifty unselected subjects living in Alpes-Maritimes, France, a high risk area for visceral leishmaniasis due to Leishmania infantum, were examined simultaneously by the leishmanin skin test and the Western blot technique in 1993; 32% and 38%, respectively, gave a positive reaction. The concordance of the 2 methods was 82%. Thus, in this high risk area, a large proportion of inhabitants had been exposed to the parasite. The use of these 2 tests should permit the detection of potential cases of reactivated leishmaniasis in prospective follow-up investigations.
TL;DR: The roles of the MAP kinase cascade have been analyzed by engineering various mutations in the kinases of the module by complementation tests, and the relationships existing between phylogenetically distant members of each kinase family have been described.