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Biomedical subjects

C Dumas

Publications and source records attributed to C Dumas.

At least 55 records · Page 3Linked to original sources
PubMed2000

Mutation of a conserved residue (D123) required for oligomerization of human immunodeficiency virus type 1 Nef protein abolishes interaction with human thioesterase and results in impairment of Nef biological functions.

Nef is a myristoylated protein of 27 to 35 kDa that is conserved in primate lentiviruses. In vivo, Nef is required for high viral load and full pathological effects. In vitro, Nef has at least four activities: induction of CD4 and major histocompatibility complex (MHC) class I downregulation, enhancement of viral infectivity, and alteration of T-cell activation pathways. We previously reported that the Nef protein from human immunodeficiency virus type 1 interacts with a novel human thioesterase (hTE). In the present study, by mutational analysis, we identified a region of the Nef core, extending from the residues D108 to W124, that is involved both in Nef-hTE interaction and in Nef-induced CD4 downregulation. This region of Nef is located on the oligomer interface and is in close proximity to the putative CD4 binding site. One of the mutants carrying a mutation in this region, targeted to the conserved residue D123, was also found to be defective in two other functions of Nef, MHC class I downmodulation and enhancement of viral infectivity. Furthermore, mutation of this residue affected the ability of Nef to form dimers, suggesting that the oligomerization of Nef may be critical for its multiple functions.

Amino Acid Sequence↗
PubMed2000

[Migraine and chronic headache in children].

In childhood and adolescence, migraine is the main essential chronic headache. This diagnosis is extensively underestimated and misdiagnosed in pediatric population. Lacks of specific biologic marker, specific investigation or brain imaging reduce these clinical entities too often to a psychological illness. Migraine is a severe headache evolving by stereotyped crises associated with marked digestive symptoms (nausea and vomiting); throbbing pain, sensitivity to sound, light are usual symptoms; the attack is sometimes preceded by a visual or sensory aura. During attacks, pain intensity is severe, most of children must lie down. Abdominal pain is frequently associated, rest brings relief and sleep ends often the attack. The prevalence of the migraine varies between 5p.100 and 10p.100 in childhood. At childhood, headache duration is quite often shorter than in adult population, it is more often frontal, bilateral (2/3 of cases) that one-sided. Migraine is a disabling illness: children with migraine lost more school days in a school year, than a matched control group. Migraine episodes are frequently triggered by several factors: emotional stress (school pressure, vexation, excitement: upset), hypoglycemia, lack of sleep or excess (week end migraine), sensorial stimulation (loud noise, bright light, strong odor, heat or cold.), sympathetic stimulation (sport, physical exercise). Attack treatments must be given at the early beginning of the crisis; oral dose of ibuprofen (10mg/kg) is recommended. If the oral route in not available when nausea or vomiting occurs, the rectal or nasal routes have then to be used. Non pharmacological treatments (biofeedback and interventions combining progressive muscle relaxation) have shown to have good efficacy as prophylactic measure. Daily prophylactic pharmacological treatments are prescribed in second line after failure of non-pharmacological treatment.

Adolescent↗
PubMed1999

Epidemiology of organic solvents and connective tissue disease.

Case reports suggest that solvents are associated with various connective tissue diseases (systemic sclerosis, scleroderma, undifferentiated connective tissue disease, systemic lupus erythematosis, and rheumatoid arthritis), particularly systemic sclerosis. A small number of epidemiological studies have shown statistically significant but weak associations between solvent exposure, systemic sclerosis, and undifferentiated connective tissue disease. However, the interpretation of these positive findings is tempered by a lack of replication, an inability to specify which solvents convey risk, and an absence of increasing risk with increasing exposure. Existing studies, on aggregate, do not show conclusively that solvents (either as a group of chemicals or individual chemicals) are causally associated with any connective tissue disease. Further investigations should be carried out to replicate the positive existing findings and to specify the solvents and circumstances of exposure that carry risk.

Connective Tissue Diseases↗
PubMed1999

Developmental patterns in the understanding of social and physical transitivity.

Transitive inferences using both a linear dimension (A is longer than B) and a nonlinear dimension (A and B are friends) were examined. In Study 1, 6- to 9-year-old children received two problems of each kind. Performance showed similar developmental progressions but nonsignificant correlations between the two tasks. Study 2 extended these results by modifying the linear transitivity problem and adding variation in both context and type of social relation. Children 7, 9, and 11 years of age were given problems requiring judgments about friendship and about nonfriends (children who were quarreling with each other) in two different social contexts. No correlations were found between social judgments and judgments concerning length. Both type of relation and context influenced judgments about social relations. These results suggest that children possess two distinct strategies for making transitive judgments that correspond to the logical structure of the underlying relations.

Child↗
PubMed1999

Novel phenotypes and developmental arrest in early embryo specific mutants of maize

Embryo specific (emb) mutants exhibit aberrant embryo development without deleterious effects on endosperm development. We have analyzed five emb mutants of maize, which, based on their developmental profiles can be divided into two groups: mutants arrested at early stages and mutants with novel phenotypes. The members of the first group resemble wild-type proembryos and never reach other developmental stages. In the second group the tube-shaped mutants emb*-8522 and emb*-8535 completely lack apical-basal differentiation, while in mutant emb*-8516 a second embryo-like structure arises from the suspensor. The five emb mutations analyzed are non-allelic and two of the mutations are very likely caused by insertion of the transposon mutator, opening the door for their molecular analysis.

Journal Article↗
PubMed1999

Analysis of in vivo immunosuppressive and in vitro interaction with constitutive heat shock protein 70 activity of LF08-0299 (Tresperimus) and analogues.

LF08-0299 (Tresperimus) is a new immunosuppressive analogue of Gusperimus (15-deoxyspergualin or DSG). Despite the fact that its mechanism of action remains unknown, DSG has previously been demonstrated to bind specifically to Hsc70 protein, a constitutive or cognate member of heat shock protein 70 family. Herein we further explore whether immobilised LF08-0299 will selectively retain the heat shock protein Hsc70. We analysed the correlation between biological activity in vivo in the prevention of murine graft-vs-host disease (GVHD) and the ability in vitro in dissociating Hsc70 from LF08-0299 resin for LF08-0299 and structural analogues. The Hsc70 protein bound to the LF08-0299 immobilised specifically via the spermidine primary amino group and could be successfully eluted from the column by various analogues of LF08-0299. All immunosuppressants tested were able to competitively bind Hsc70 although some biological inactive compounds could as well. Our data suggests that LF08-0299 and its active analogue effects were not mediated directly through the interaction of molecules with Hsc70. The mechanism of action probably occurred by more than one step, the first being the binding of Hsc70.

Animals↗
PubMed1999

Membrane proteins involved in pollen-pistil interactions.

Self-incompatibility (SI) is a widespread mechanism in angiosperms which prevents self-fertilization. This mechanism relies on cell-cell interactions between pollen and pistil. Among the different SI systems that have been reported, two have been particularly investigated: the gametophytic system of Solanaceae and the sporophytic system of Brassicaceae. In these two families, although the molecular bases of SI response are different, secreted and/or membrane-anchored proteins are required for self-pollen rejection. Interestingly, these proteins exhibit two functions: recognition and a catalytic activity. In this review article, we present recent advances which permit a better understanding of how these proteins control the male/female recognition event associated with the SI response.

Animals↗
PubMed1999

Identification of a gene linked to the Brassica S (self-incompatibility) locus by differential display.

Self-incompatibility in Brassica is controlled by a complex locus, the S locus, that includes several expressed genes. Two S locus genes, SLG and SRK, are expressed in the stigma and have been implicated in self-pollen recognition. The male component of this recognition system is also predicted to be encoded by a gene at the S locus but this gene has not been identified to date. In this study, we have used differential display to screen for polymorphic, S-locus-linked genes that are expressed in anthers. This approach has allowed the identification of a gene, named S5J, which was shown to segregate completely with the S locus. We discuss the possible role of this gene in the self-incompatibility response and evaluate the utility of differential display for the identification of genes at specific genetic loci.

Base Sequence↗
PubMed1999

ZmOCL1, an HDGL2 family homeobox gene, is expressed in the outer cell layer throughout maize development.

The formation of a morphologically distinct outer cell layer or protoderm is one of the first and probably one of the most important steps in patterning of the plant embryo. Here we report the isolation of ZmOCL1 (OCL for outer cell layer), a member of the HDGL2 (also known as HD-ZIP IV) subclass of plant-specific HD-ZIP homeodomain proteins from maize. ZmOCL1 transcripts are detected very early in embryo development, before a morphologically distinct protoderm is visible, and expression then becomes localised to the protoderm of the embryo as it develops. Subsequently, expression is observed in the L1 cell layer of both the developing primary root and shoot meristems, and is maintained in developing leaves and floral organs. We propose that ZMOCL1 may play a role in the specification of protoderm identity within the embryo, the organisation of the primary root primordium or in the maintenance of the L1 cell layer in the shoot apical meristem. We also show that the expression of ZmOCL1 is different from that of another epidermal marker gene, LTP2 (lipid transfer protein) and, in meristems, is complementary to that of Kn1 (Knotted) which is transcribed only in underlying cell layers.

Amino Acid Sequence↗
PubMed1999

Pollen-stigma adhesion in Brassica spp involves SLG and SLR1 glycoproteins.

The adhesion of pollen grains to the stigma is the first step of pollination in flowering plants. During this step, stigmas discriminate between pollen grains that can and cannot be permitted to effect fertilization. This selection is operated by various constituents of the cell walls of both partners. Several genes structurally related to the self-incompatibility system that prevents self-pollination in Brassica spp are known to target their products into the stigma cell wall. We proposed previously that one of these genes, the one encoding the S locus glycoprotein (SLG)-like receptor 1 (SLR1), which is coexpressed with that encoding SLG, may participate in pollen-stigma adhesion. Here, we exploit a biomechanical assay to measure the pollen adhesion force and show that it is reduced both by transgenic suppression of SLR1 expression and by pretreatment of wild-type stigmas with anti-SLR1 antibodies, anti-SLG antibodies, or pollen coat-protein extracts. Our results indicate a common adhesive function for the SLR1 and SLG proteins in the pollination process.

Antibodies↗
PubMed1999

The S15 self-incompatibility haplotype in Brassica oleracea includes three S gene family members expressed in stigmas.

Self-incompatibility in Brassica is controlled by a single, highly polymorphic locus that extends over several hundred kilobases and includes several expressed genes. Two stigma proteins, the S locus receptor kinase (SRK) and the S locus glycoprotein (SLG), are encoded by genes located at the S locus and are thought to be involved in the recognition of self-pollen by the stigma. We report here that two different SLG genes, SLGA and SLGB, are located at the S locus in the class II, pollen-recessive S15 haplotype. Both genes are interrupted by a single intron; however, SLGA encodes both soluble and membrane-anchored forms of SLG, whereas SLGB encodes only soluble SLG proteins. Thus, including SRK, the S locus in the S15 haplotype contains at least three members of the S gene family. The protein products of these three genes have been characterized, and each SLG glycoform was assigned to an SLG gene. Evidence is presented that the S2 and S5 haplotypes carry only one or the other of the SLG genes, indicating either that they are redundant or that they are not required for the self-incompatibility response.

Alleles↗
PubMed1998

RT loop flexibility enhances the specificity of Src family SH3 domains for HIV-1 Nef.

Understanding the issue of specificity imposed in the interactions of SH3 domains has largely been addressed in studies investigating the interaction of proline-rich amino acid sequences derived from potential ligands for these domains. Although the interaction with this motif forms an essential platform in the binding of SH3 domains, in many cases little specificity is observed and the difference in affinity for so-called specific and nonspecific proline-rich sequences is not great. Furthermore, the binding interface between an SH3 domain and a protein ligand appears to encompass more interactions than are represented by that involving the proline-rich motif. Here we investigate the issue of specificity from the opposite point of view; namely, how does a ligand recognize different SH3 domains? We present the crystal structure of the unbound SH3 domain from hemopoietic cell kinase (Hck) which is a member of the Src family of tyrosine kinases. This structure reveals that, unlike the structures of other Src kinase SH3 domains, the RT loop region is highly mobile and lacks a network of hydrogen bonds that is elsewhere apparent. The RT loop has been shown to form a major part of the binding interface between SH3 domains and HIV-1 Nef. Thermodynamic data, derived from isothermal titration calorimetry, for the binding of Hck SH3 to HIV-1 Nef show that the binding of Hck (KD = 1.5 microM) is approximately an order of magnitude tighter than those of other Src family kinases that were investigated (Fyn, Lck, and Src). This increase in affinity is attributed to, among other effects, the inherent flexibility in the RT loop which does not require breaking the network of hydrogen bonds to adopt the conformation required for binding.

Amino Acid Sequence↗
PubMed1998

The relation between accuracy of self-perception and cognitive development.

BACKGROUND: It is now widely recognised that student's self-perceptions of competence have an effect on their behaviours and learning. Previous studies have shown that children only gradually develop the ability to evaluate accurately their own competence. One possible explanation for this is that younger children have not reached a level of cognitive development required to perform such evaluations. AIMS: The objective of these two studies was to examine the hypothesis that children at higher levels of cognitive development should be more accurate in their self-appraisal of competence than children of the same age at lower levels of cognitive development. STUDY 1. SAMPLE: The sample included 173 elementary school children, with almost equal gender representation. Children were first examined in fourth grade (mean age = 10.0, SD = .77) and for the next two years. METHOD: Each child responded to questionnaires of self-perceptions about reading and to a standardised test of reading. Year-end grades in reading were used as a measure of performance. RESULTS: The results show that there was no significant difference between high and low children in grade 6, but that the correlation between self-perceptions and performance was significantly higher among high ability children than among low ability children both in grades 4 and 5. STUDY 2. SAMPLE: The sample included 153 elementary school children in grade 3 (mean age = 9.1, SD = .73) and 185 in grade 5 (mean age = 11.2, SD = .75), with almost equal gender representation. METHOD: Each child responded to questionnaires of self-perceptions about mathematics and to a standardised IQ test. Year-end grades in mathematics were used as a measure of performance. RESULTS: The correlation between self-perception and performance was significantly higher among high IQ children than among low IQ children in grade 3. However, in grade 5, high and low IQ children were similarly accurate in their self-perceptions. CONCLUSIONS: These results suggest that the development of accurate self-perceptions is not strictly a matter of age or school level but is also related to cognitive development.

Child↗
PubMed1997

Parameters controlling the rate of gene targeting frequency in the protozoan parasite Leishmania.

In this study we investigated the role of several parameters governing the efficiency of gene targeting mediated by homologous recombination in the protozoan parasite Leishmania. We evaluated the relative targeting frequencies of different replacement vectors designed to target several sequences within the parasite genome. We found that a decrease in the length of homologous sequences <1 kb on one arm of the vector linearly influences the targeting frequency. No homologous recombination was detected, however, when the flanking homologous regions were <180 bp. A requirement for a very high degree of homology between donor and target sequences was found necessary for efficient gene targeting in Leishmania , as targeted recombination was strongly affected by base pair mismatches. Targeting frequency increased proportionally with copy number of the target only when the target was part of a linear amplicon, but remained unchanged when it was present on circles. Different chromosomal locations were found to be targeted with significantly variable levels of efficiency. Finally, different strains of the same species showed differences in gene targeting frequency. Overall, gene targeting mediated by homologous recombination in Leishmania shares similarities to both the yeast and the mammalian recombination systems.

Animals↗
PubMed1997

The crystal structure of HIV-1 Nef protein bound to the Fyn kinase SH3 domain suggests a role for this complex in altered T cell receptor signaling.

BACKGROUND: Human immunodeficiency virus (HIV) Nef protein accelerates virulent progression of acquired immunodeficiency syndrome (AIDS) by its interaction with specific cellular proteins involved in signal transduction and host cell activation. Nef has been shown to bind specifically to a subset of the Src family of kinases. The structures of free Nef and Nef bound to Src homology region 3 (SH3) domain are important for the elucidation of how the affinity and specificity for the Src kinase family SH3 domains are achieved, and also for the development of potential drugs and vaccines against AIDS. RESULTS: We have determined the crystal structures of the conserved core of HIV-1 Nef protein alone and in complex with the wild-type SH3 domain of the p59fyn protein tyrosine kinase (Fyn), at 3.0 A resolution. Comparison of the bound and unbound Nef structures revealed that a proline-rich motif (Pro-x-x-Pro), which is implicated in SH3 binding, is partially disordered in the absence of the binding partner; this motif only fully adopts a left-handed polyproline type II helix conformation upon complex formation with the Fyn SH3 domain. In addition, the structures show how an arginine residue (Arg77) of Nef interacts with Asp 100 of the so-called RT loop within the Fyn SH3 domain, and triggers a hydrogen-bond rearrangement which allows the loop to adapt to complement the Nef surface. The Arg96 residue of the Fyn SH3 domain is specifically accommodated in the same hydrophobic pocket of Nef as the isoleucine residue of a previously described Fyn SH3 (Arg96-->lle) mutant that binds to Nef with higher affinity than the wild type. CONCLUSIONS: The three-dimensional structures support evidence that the Nef-Fyn complex forms in vivo and may have a crucial role in the T cell perturbating action of Nef by altering T cell receptor signaling. The structures of bound and unbound Nef reveal that the multivalency of SH3 binding may be achieved by a ligand induced flexibility in the RT loop. The structures suggest possible targets for the design of inhibitors which specifically block Nef-SH3 interactions.

Amino Acid Sequence↗
PubMed1997

Crystal structure of a new RNA-binding domain from the antiterminator protein SacY of Bacillus subtilis.

SacY belongs to a family of, at present, seven bacterial transcriptional antiterminators. The RNA-binding and antitermination capacity of SacY resides in the 55 amino acids at the N-terminal [SacY(1-55)]. The crystal structure at 2 A resolution shows that SacY(1-55) forms a dimer in the crystal, in accordance with the NMR solution structure. The structure of the monomer is a four-stranded beta-sheet with a simple beta1beta2beta3beta4 topology. One side of the sheet is covered by a long surface loop and the other side forms the dimer interface. The dimer is stabilized by the orthogonal stacking of the two beta-sheets. The crystal structure is in excellent agreement with the NMR solution structure (r.m.s. distance for C alpha coordinates is 1.3 A). The structure of SacY(1-55) reveals a new RNA-binding motif.

Amino Acid Sequence↗
PubMed1997

Disruption of the trypanothione reductase gene of Leishmania decreases its ability to survive oxidative stress in macrophages.

Parasitic protozoa belonging to the order Kinetoplastida contain trypanothione as their major thiol. Trypanothione reductase (TR), the enzyme responsible for maintaining trypanothione in its reduced form, is thought to be central to the redox defence systems of trypanosomatids. To investigate further the physiological role of TR in Leishmania, we attempted to create TR-knockout mutants by gene disruption in L. donovani and L. major strains using the selectable markers neomycin and hygromycin phosphotransferases. TR is likely to be an important gene for parasite survival since all our attempts to obtain a TR null mutant in L. donovani failed. Instead, we obtained mutants with a partial trisomy for the TR locus where, despite the successful disruption of two TR alleles by gene targeting, a third TR copy was generated as a result of genomic rearrangements involving the translocation of a TR-containing region to a larger chromosome. Mutants of L. donovani and L. major possessing only one wild-type TR allele express less TR mRNA and have lower TR activity compared with wild-type cells carrying two copies of the TR gene. Significantly, these mutants show attenuated infectivity with a markedly decreased capacity to survive intracellularly within macrophages, provided that the latter are producing reactive oxygen intermediates.

Animals↗