Showing papers by "Centre national de la recherche scientifique published in 1991"
TL;DR: Collagen molecules are structural macromolecules of the extracellular matrix that include in their structure one or several domains that have a characteristic triple helical conformation and play the role of connecting elements between these major structures and other tissue components.
Abstract: Collagen molecules are structural macro-molecules of the extracellular matrix that include in their structure one or several domains that have a characteristic triple helical conformation. They have been classified by types that define distinct sets of polypeptide chains that can form homo- and heterotrimeric assemblies. All the collagen molecules participate in supramolecular aggregates that are stabilized in part by interactions between triple helical domains. Fourteen collagen types have been defined so far. They form a wide range of structures. Most notable are 1) fibrils that are found in most connective tissues and are made by alloys of fibrillar collagens (types I, II, III, V, and XI) and 2) sheets constituting basement membranes (type IV collagen), Descemet's membrane (type VIII collagen), worm cuticle, and organic exoskeleton of sponges. Other collagens, present in smaller quantities in tissues, play the role of connecting elements between these major structures and other tissue components. The f...
1,217 citations
TL;DR: An enumerative method is proposed in order to exhaustively validate the behavior of Merlin's time Petri net model and it is applied to the specification and verification of the alternating bit protocol as a simple illustrative example.
Abstract: A description and analysis of concurrent systems, such as communication systems, whose behavior is dependent on explicit values of time is presented. An enumerative method is proposed in order to exhaustively validate the behavior of P. Merlin's time Petri net model, (1974). This method allows formal verification of time-dependent systems. It is applied to the specification and verification of the alternating bit protocol as a simple illustrative example. >
1,129 citations
TL;DR: The respiratory epithelium is a potential site for somatic gene therapy for the common hereditary disorders alpha 1-antitrypsin (alpha 1AT) deficiency and cystic fibrosis by infecting epithelial cells of the cotton rat respiratory tract in vitro and in vivo.
Abstract: The respiratory epithelium is a potential site for somatic gene therapy for the common hereditary disorders alpha 1-antitrypsin (alpha 1AT) deficiency and cystic fibrosis. A replication-deficient adenoviral vector (Ad-alpha 1AT) containing an adenovirus major late promoter and a recombinant human alpha 1AT gene was used to infect epithelial cells of the cotton rat respiratory tract in vitro and in vivo. Freshly isolated tracheobronchial epithelial cells infected with Ad-alpha 1AT contained human alpha 1AT messenger RNA transcripts and synthesized and secreted human alpha 1AT. After in vivo intratracheal administration of Ad-alpha 1AT to these rats, human alpha 1AT messenger RNA was observed in the respiratory epithelium, human alpha 1AT was synthesized and secreted by lung tissue, and human alpha 1AT was detected in the epithelial lining fluid for at least 1 week.
975 citations
TL;DR: The results demonstrate that neurons possess an efficient uptake system for the antennapedia homeobox peptide and suggest that binding of pAntp to consensus motifs present in nerve cell nuclei influences neuronal morphogenetic programs.
Abstract: We synthesized the 60-amino acid polypeptide corresponding to the sequence of the Drosophila antennapedia gene homeobox. This peptide (pAntp) recognized the consensus motif for binding to the promoter region of Hox-1.3. pAntp mechanically introduced into mammalian nerve cells provoked a dramatic morphological differentiation of the neuronal cultures. Moreover, pAntp directly added to already differentiated neuronal cultures penetrated the cells and further augmented their morphological differentiation. Examination of live and fixed neurons in classical and confocal fluorescence microscopy demonstrated that pAntp was captured at all regions of the nerve cells and accumulated in the nuclei. In addition, the effect of pAntp on neurite extension was blocked in the presence of the protein synthesis inhibitor cycloheximide. Thus, our results demonstrate that neurons possess an efficient uptake system for the antennapedia homeobox peptide and suggest that binding of pAntp to consensus motifs present in nerve cell nuclei influences neuronal morphogenetic programs.
737 citations
TL;DR: In this article, a mixed penalty-duality formulation of the frictional contact problem, inspired from an augmented Lagrangian approach, was proposed, and sufficient conditions for their convergence were conjectured.
Abstract: A mixed penalty-duality formulation of the frictional contact problem, inspired from an augmented Lagrangian approach is proposed. The continuity of the resulting conewise linear operator is used to establish a uniqueness condition on the coefficient of friction. Modified and generalized Newton methods are examined and sufficient conditions for their convergence conjectured. A cylindrical frictional contact problem assesses the stability of the method. Mixed penalty-duality methods are found more accurate and stabler than penalty methods and as economical as them.
723 citations
TL;DR: A review of the state of the art in the field of chemistry of the NO 3 radical is presented in this paper, with a focus on the relationship between the laboratory and the atmospheric studies.
694 citations
TL;DR: The ability to express the human cannabinoid receptor in mammalian cells should help in developing more selective drugs, and should facilitate the search for the endogenous cannabinoid ligand(s).
Abstract: A cDNA clone encoding a receptor protein which presents all the characteristics of a guanine-nucleotide-binding protein (G-protein)-coupled receptor was isolated from a human brain stem cDNA library. The probe used (HGMP08) was a 600 bp DNA fragment amplified by a low-stringency PCR, using human genomic DNA as template and degenerate oligonucleotide primers corresponding to conserved sequences amongst the known G-protein-coupled receptors. The deduced amino acid sequence encodes a protein of 472 residues which shares 97.3% identity with the rat cannabinoid receptor cloned recently [Matsuda, Lolait, Brownstein, Young & Bronner (1990) Nature (London) 346, 561-564]. Abundant transcripts were detected in the brain, as expected, but lower amounts were also found in the testis. The same probe was used to screen a human testis cDNA library. The cDNA clones obtained were partially sequenced, demonstrating the identity of the cannabinoid receptors expressed in both tissues. Specific binding of the synthetic cannabinoid ligand [3H]CP55940 was observed on membranes from Cos-7 cells transfected with the recombinant receptor clone. In stably transfected CHO-K1 cell lines, cannabinoid agonists mediated a dose-dependent and stereoselective inhibition of forskolin-induced cyclic AMP accumulation. The ability to express the human cannabinoid receptor in mammalian cells should help in developing more selective drugs, and should facilitate the search for the endogenous cannabinoid ligand(s).
678 citations
TL;DR: Within the same region of the presumptive hindbrain, two HOX-1 genes are involved in the patterning of two different populations of neural crest cells, and the implication of these results for the function of the Hox network during mouse embryogenesis is discussed.
677 citations
TL;DR: A new human cyclin, named cyclin E, was isolated by complementation of a triple cln deletion in S. cerevisiae, suggesting that it functioned at START by interacting with the CDC28 protein.
663 citations
TL;DR: Two candidate exons, identified by multiparameter computer programs, were found in a cDNA encoding a protein of 679 amino acids that encodes a putative adhesion molecule, consistent with the defect of embryonic neuronal migration.
655 citations
TL;DR: This structure-activity relationship study shows that inhibition of microtubule disassembly is quite sensitive to the configuration at C-2' and C-3'.
Abstract: A variety of synthetic analogues of taxol, a naturally occurring antitumor diterpene, were examined for their potency to inhibit microtubule disassembly. For some of the compounds, the in vitro cytotoxic properties showed a good correlation with the tubulin assay. This structure-activity relationship study shows that inhibition of microtubule disassembly is quite sensitive to the configuration at C-2' and C-3'. A correlation between the conformation of the side chain at C-13 and the activity is suggested. Of all the compounds examined, one of the most potent in inhibiting microtubule disassembly and in inhibiting murine P388 leukemic cells, N-debenzoyl-N-tert-(butoxycarbonyl)-10-deacetyltaxol, named taxotere, was selected for evaluation as a potential anticancer agent.
TL;DR: Using PCR and RNAase protection analysis, this gene, termed CREM, is isolated from a mouse pituitary cDNA library and three mRNA isoforms are identified that appear to be obtained by differential cell-specific splicing.
TL;DR: The crystal structure of the binary complex tRNA(Asp)-aspartyl tRNA synthetase from yeast was solved with the use of multiple isomorphous replacement to 3 angstrom resolution.
Abstract: The crystal structure of the binary complex tRNA(Asp)-aspartyl tRNA synthetase from yeast was solved with the use of multiple isomorphous replacement to 3 angstrom resolution. The dimeric synthetase, a member of class II aminoacyl tRNA synthetases (aaRS's) exhibits the characteristic signature motifs conserved in eight aaRS's. These three sequence motifs are contained in the catalytic site domain, built around an antiparallel beta sheet, and flanked by three alpha helices that form the pocket in which adenosine triphosphate (ATP) and the CCA end of tRNA bind. The tRNA(Asp) molecule approaches the synthetase from the variable loop side. The two major contact areas are with the acceptor end and the anticodon stem and loop. In both sites the protein interacts with the tRNA from the major groove side. The correlation between aaRS class II and the initial site of aminoacylation at 3'-OH can be explained by the structure. The molecular association leads to the following features: (i) the backbone of the GCCA single-stranded portion of the acceptor end exhibits a regular helical conformation; (ii) the loop between residues 320 and 342 in motif 2 interacts with the acceptor stem in the major groove and is in contact with the discriminator base G and the first base pair UA; and (iii) the anticodon loop undergoes a large conformational change in order to bind the protein. The conformation of the tRNA molecule in the complex is dictated more by the interaction with the protein than by its own sequence.
TL;DR: The results indicate that the unpaired electron in P+ does not share a molecular orbital common to the two components of the dimer on the time scale of the resonance Raman effect, and the understanding of charge separation and stabilization requires a thorough characterization of the physicochemical properties of P.
Abstract: Preresonance Raman and resonance Raman spectra of the primary donor (P) from reaction centers of the Rhodobacter (Rb. ) sphaeroides R26 carotenoidless strain in the P and P+ states, respectively, were obtained at room temperature with 1064-nm excitation and a Fourier transform spectrometer. These spectra clearly indicate that the chromophore modes are observable over those of the protein with no signs of interference below 1800 cm-*. The chromophore modes are dominated by those of the bacteriochlorophylls (BChl a) , and it is estimated that, in the P state, ca. 65% of the Raman intensity of the BChl a modes arises from the primary donor. This permits the direct observation of a vibrational spectrum of the primary donor at preresonance with the excitonic 865-nm band. The Raman spectrum of oxidized reaction centers in the presence of ferricyanide clearly exhibits bands arising from a BChl a+ species. The magnitude of the frequency shift of a keto carbonyl of neutral P from 1691 to 17 17 cm-' upon P+ formation strongly suggests that one BChl molecule in P+ carries nearly the full +1 charge. Our results indicate that the unpaired electron in P+ does not share a molecular orbital common to the two components of the dimer on the time scale of the resonance Raman effect (ca. s). x e primary events in bacterial photosynthesis occur in membrane-bound proteins known as reaction centers (RCs).' The isolated RC consists of six bacteriochlorin pigments (four bacteriochlorophyll a and two bacteriopheophytin a molecules), two quinones, one non-heme iron, one carotenoid molecule, and approximately 850 amino acid residues contained in three. polypeptide subunits named L, M, and H. Within the RC, electron transfer originates from the primary donor P, which consists of a pair of bacteriochlorophyll (BChl) molecules in mutual excitonic interaction. Although the X-ray crystallographic structures of the RC from Rhodopseudomonas (Rps.) viridis (Deisenhofer & Michel, 1989) and Rhodobacter (Rb.) sphaeroides (Allen et al., 1987a,b; Chang et al., 1986; T i d e et ai., 1988) are resolved, the understanding of charge separation and stabilization requires a thorough characterization of the physicochemical properties of P and its cation radical, P+. The absorption spectrum of bacterial reaction centers exhibits a broad band in the near-infrared that corresponds to the first excited singlet state of the primary donor pair, 'P. For bacteriochlorophyll a (BChl a ) containing RCs, such as Rb. sphaeroides, this band appears at ca. 870 nm. The characterization of this band in an attempt to explain the asymmetric functioning of the RC has been the subject of recent intensive work [for a review, see Friesner and Won (1989)]. When P undergoes one-electron chemical or phoT.A.M. gratefully acknowledges fellowships from NATO/NSERC Abbreviations: RR, resonance Raman; NIR, near-infrared; FT, Fourier transform; RC, reaction center; Rb., Rhodobacter; Rps., Rhodopseudomonas; Rsp., Rhodospirillum; BChl, bacteriochlorophyll; BPhe, bacteriopheophytin; EPR, electron paramagnetic resonance; THF, tet(Canada) and EMBO. *Author to whom correspondence should be addressed. *CE Saclay. * Universitit Essen. rahydrofuran. 0006-2960/9 1 /0430-4648$02.50/0 0 199 1 American Chemical Society
TL;DR: The above results, in view of previous findings for postsynaptic effects of norepinephrine, are interpreted to reveal a role for the LC system in regulating attentional state or vigilance.
Abstract: Recordings from noradrenergic locus coeruleus (LC) neurons in behaving rats and monkeys revealed that these cells decrease tonic discharge during sleep and also during certain high arousal behaviors (grooming and consumption) when attention (vigilance) was low. Sensory stimuli of many modalities phasically activated LC neurons. Response magnitudes varied with vigilance, similar to results for tonic activity. The most effective and reliable stimuli for eliciting LC responses were those that disrupted behavior and evoked orienting responses. Similar results were observed in behaving monkeys except that more intense stimuli were required for LC responses. Our more recent studies have examined LC activity in monkeys performing an “oddball” visual discrimination task. Monkeys were trained to release a lever after a target cue light that occurred randomly on 10% of trials; animals had to withhold responding during non-target cues. LC neurons selectively responded to the target cues during this task. During reversal training, LC neurons lost their response to the previous target cue and began responding to the new target light in parallel with behavioral reversal. Cortical event-related potentials were elicited in this task selectively by the same stimuli that evoked LC responses. Injections of lidocaine, GABA, or a synaptic decoupling solution into the nucleus paragigantocellularis in the rostral ventrolateral medulla, the major afferent to LC, eliminated responses of LC neurons to sciatic nerve stimulation or foot-or tail-pinch. This indicates that certain sensory information is relayed to LC through the excitatory amino acid (EAA) input from the ventrolateral medulla. The effect of prefrontal cortex (PFC) activation on LC neurons was examined in anesthetized rats. Single pulse PFC stimulation had no pronounced effect on LC neurons, consistent with our findings that this area does not innervate the LC nucleus. However, trains of PFC stimulation substantially activated most LC neurons. Thus, projections from the PFC may activate LC indirectly or through distal dendrites, suggesting a circuit whereby complex stimuli may influence LC neurons. The above results, in view of previous findings for postsynaptic effects of norepinephrine, are interpreted to reveal a role for the LC system in regulating attentional state or vigilance. The roles of major inputs to LC from the ventrolateral and dorsomedial medulla in sympathetic control and behavioral orienting responses, respectively, are integrated into this view of the LC system. It is proposed that the LC provides the cognitive complement to sympathetic function.
TL;DR: In this article, a 13,000-yr record from Sumxi Co (western Tibet), constructed from both lake-core and shoreline studies, shows that conditions in the early-middle Holocene were warmer and wetter than at present.
Abstract: ALTHOUGH the Tibetan plateau is important in influencing the atmospheric circulation of the Northern Hemisphere1–3, there are only a few continuous palaeoclimate records available, and these are limited to the plateau's northeastern margin4–6. Here we present a 13,000-yr record from Sumxi Co (western Tibet), constructed from both lake-core and shoreline studies, which shows that conditions in the early–middle Holocene were warmer and wetter than at present. These results confirm model predictions of an intensified monsoon over the region at ∼9,000 yr BP, owing to an orbitally induced increase in summer insolation7,8. We also find evidence for warm, humid pulses at ∼12,500 and ∼10,000 yr BP, in phase with the steps of the last deglaciation, and for a return to cold, dry conditions at ∼11-10,000 yr BP, none of which can be explained by orbital variations. The existence of the cold episode confirms that the cooling associated with the Younger Dry as event occurred in continental China6,9, and provides further evidence of the global nature of this event10
TL;DR: Investigation of how structural elements could be involved in the desensitization of the acetylcholine-gated ion channel from the chick brain α-bungarotoxin sensitive homo-oligomeric α7 receptor using site-directed mutagenesis and expression in Xenopus oocytes finds that leucine-to-threonine mutant has an additional conducting state active at low acetylCholine concentrations.
Abstract: A variety of ligand-gated ion channels undergo a fast activation process after the rapid application of agonist and also a slower transition towards desensitized or inactivated closed channel states when exposure to agonist is prolonged. Desensitization involves at least two distinct closed states in the acetylcholine receptor, each with an affinity for agonists higher than those of the resting or active conformations. Here we investigate how structural elements could be involved in the desensitization of the acetylcholine-gated ion channel from the chick brain alpha-bungarotoxin sensitive homo-oligomeric alpha 7 receptor, using site-directed mutagenesis and expression in Xenopus oocytes. Mutations of the highly conserved leucine 247 residue from the uncharged MII segment of alpha 7 suppress inhibition by the open-channel blocker QX-222, indicating that this residue, like others from MII, faces the lumen of the channel. But, unexpectedly, the same mutations decrease the rate of desensitization of the response, increase the apparent affinity for acetylcholine and abolish current rectification. Moreover, unlike wild-type alpha 7, which has channels with a single conductance level, the leucine-to-threonine mutant has an additional conducting state active at low acetylcholine concentrations. It is possible that mutation of Leu 247 renders conductive one of the high-affinity desensitized states of the receptor.
TL;DR: A highly specific prokaryotic lipo-oligosaccharide signal is able to trigger a genuine organogenesis in a higher plant and elicit cortical cell divisions and the formation of genuine nodules on aseptically grown seedlings of alfalfa.
Abstract: RHIZOBIUM meliloti is a symbiotic bacterium that elicits the morphogenesis of nitrogen-fixing nodules, specific organs on the roots of alfalfa (Medicago sativa)1. In R. meliloti a series of nodulation (nod) genes have been identified which are involved in root-hair curling and infection and in nodule formation1. The nodABC genes, common to all Rhizobium sp., and the host-range nodH and nodPQ genes are involved in the production of an excreted root-hair deforming factor, NodRm-1, which is a sul-phated and acylated glucosamine oligosaccharide2–7. Here we report that purified NodRm-1 and a related compound, Ac-Nod Rm-1, at concentrations in the micromolar–nanomolar range, elicit cortical cell divisions and the formation of genuine nodules on aseptically grown seedlings of alfalfa. Chemical modifications of NodRm-1, such as the removal of the sulphate group, reduction of the terminal sugar or hydrogenation of the acyl chain result in a strong decrease in the morphogenic activity. A highly specific prokaryotic lipo-oligosaccharide signal is thus able to trigger a genuine organogenesis in a higher plant.
TL;DR: It is demonstrated that dopamine acts on efferent striatal neurons through expression of distinct receptors--namely, D1 and D2 in separate cell populations (substance P and preproenkephalin A neurons, respectively)--and can also act on nonprojecting neurons through D1 receptor expression.
Abstract: In situ hybridization experiments were performed in rat brain sections from normal and 6-hydroxydopamine-treated rats in order to map and identify the neurons expressing the D1 receptor gene in the striatum and the substantia nigra. Procedures of combined in situ hybridization, allowing the simultaneous detection of two mRNAs in the same section or in adjacent sections, were used to characterize the phenotypes of the neurons expressing the D1 receptor gene. D1 receptor mRNA was found in neurons all over the caudate-putamen, the accumbens nucleus, and the olfactory tubercle but not in the substantia nigra. In the caudate-putamen and accumbens nucleus, most of the neurons containing D1 receptor mRNA were characterized as medium-sized substance P neurons and distinct from those containing D2 receptor mRNA. Nevertheless, 15-20% of the substance P neurons did not contain D1 receptor mRNA. The neurons containing preproenkephalin A mRNA did not contain D1 receptor mRNA but contained D2 receptor mRNA. A small number of cholinergic and somatostatinergic neurons exhibited a weak reaction for D1 receptor mRNA. These results demonstrate that dopamine acts on efferent striatal neurons through expression of distinct receptors--namely, D1 and D2 in separate cell populations (substance P and preproenkephalin A neurons, respectively)--and can also act on nonprojecting neurons through D1 receptor expression.
TL;DR: In this article, the authors used data collected from 1975 to 1987 to estimate carbon dioxide emissions from the summit craters and the upper flanks of the volcano and found that the average output of CO2 from summit crater degassing is 13±3 Tg yr−1, an order of magnitude higher than the annual CO2 output from Kilauea, Hawaii, and representative arc volcanoes.
Abstract: MOUNT Etna, in Sicily, is one of the world's most actively degassing volcanoes1. Here we use data collected from 1975 to 1987 to estimate carbon dioxide emissions from the summit craters and the upper flanks of the volcano. By combining measurements of the SO2 flux in the plume (refs 1–6 and this paper) with measurements of the CO2/SO2 ratio of the plume gases, we find that the average output of CO2 from summit crater degassing is 13±3 Tg yr−1. This is an order of magnitude higher than the annual CO2 output from Kilauea7,8, Hawaii, and representative arc volcanoes9,10. Furthermore, we find that diffuse emissions of CO2 from the upper flanks of Etna are magma-derived and are of a similar magnitude to those emitted from the crater plume. This observation, as well as others11–14, verifies the idea15 that extensive diffuse release of magmatic CO2 may occur in volcanically active regions—a process that needs to be taken into account when evaluating the volatile budget of subaerial volcanism. Such degassing may be of use for monitoring volcanic activity, could provide a means for radiocarbon dating of eruptions, and may be a mechanism by which CO2 is injected into crater lakes.
TL;DR: Comparison between gene expression level and vector copy-number indicated that a plateau in delta-endotoxin production is reached with a copy- number of about fifteen per equivalent chromosome.
TL;DR: In this article, a pseudo-spectral Chebyshev algorithm was used to solve the equations of natural convection in a 2D differentially heated cavity with adiabatic top and bottom walls for values of Ra up to 108.
TL;DR: Results provide strong evidence that the molecular mechanism by which the nodH and nodPQ genes mediate host specificity is by determining the sulfation of the extracellular Nod signals.
TL;DR: Factorial Correspondence Analysis found that three classes ought to be included in order to match all data now available, and suggested that bacterial strains cultivated in the laboratory have been fixed by specific use of antimutator genes that are horizontally exchanged.
TL;DR: Measurement of cardiac and respiratory activity during mental simulation of locomotion at increasing speed revealed a covariation of heart rate and pulmonary ventilation with the degree of imagined effort, suggestive of a commonality of neural structures responsible for mental imagery of movement and those responsible for programming actual movement.
TL;DR: A review of the different ways to prepare cubic boron nitride (BN) is given in this article, where the physical and chemical properties and the correlated industrial or potential applications are shown.
Abstract: A review, with 112 references, is given of the different ways to prepare cubic boron nitride (BN). The different crystal forms as well as the phase diagram of BN are described. The physical and chemical properties and the correlated industrial or potential applications are shown.
TL;DR: The results strongly suggest that the trans-activation function of TEF-1 is mediated by a highly limiting, possible cell-specific, titratable transcriptional intermediary factor(s).
TL;DR: In this article, the authors present a space-time description of regular and complex phenomena which consists of a decomposition of a spatio-temporal signal into orthogonal temporal modes that are called chronos and orthogonal spatial modes that they call topos, and they show a direct relation between the global entropy and the different instabilities that the flow undergoes as Reynolds number increases.
Abstract: We present a space-time description of regular and complex phenomena which consists of a decomposition of a spatiotemporal signal into orthogonal temporal modes that we call chronos and orthogonal spatial modes that we call topos. This permits the introduction of several characteristics of the signal, three characteristic energies and entropies (one temporal, one spatial, and one global), and a characteristic dimension. Although the technique is general, we concentrate on its applications to hydrodynamic problems, specifically the transition to turbulence. We consider two cases of application: a coupled map lattice as a dynamical system model for spatiotemporal complexity and the open flow instability on a rotating disk. In the latter, we show a direct relation between the global entropy and the different instabilities that the flow undergoes as Reynolds number increases.
TL;DR: Observations indicate that the cytopathic effect of HIV infection is associated with apoptosis and the detection of histones and oligonucleosomal DNA fragments in the nucleoplasm can be used as a convenient marker for chromatin fragmentation during this process.