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Biomedical subjects

M Mathieu

Publications and source records attributed to M Mathieu.

At least 145 records · Page 8Linked to original sources
PubMed1995

X-linked progressive mixed deafness: a new microdeletion that involves a more proximal region in Xq21.

We report a large two-generation pedigree with seven affected males segregating for an X-linked mixed conductive sensorineural deafness. The patients present with atypical Mondini-like dysplasia, dilated petrous facial canal, dilatation of the internal auditory meatus fully connected with enlarged cochlear canals, and, in one patient, a wide bulbous posterior labyrinth. Obligatory carrier females are mildly affected. Molecular characterization of this family revealed a deletion of locus DXS169, in Xq21.1. Loci DXS72 and DXS26, which, respectively, flank DXS169 proximally and distally, were intact. Since a gene responsible for X-linked progressive mixed deafness with perilymphatic gusher (DFN3) has previously been assigned by deletion mapping to a slightly more distal interval between DXS26 and DXS121, this study indicates either two different deafness genes or the involvement of a very large region in Xq21.

Ear, Inner↗
PubMed1994

The 2.8 A crystal structure of peroxisomal 3-ketoacyl-CoA thiolase of Saccharomyces cerevisiae: a five-layered alpha beta alpha beta alpha structure constructed from two core domains of identical topology.

BACKGROUND: The peroxisomal enzyme 3-ketoacyl-coenzyme A thiolase of the yeast Saccharomyces cerevisiae is a homodimer with 417 residues per subunit. It is synthesized in the cytosol and subsequently imported into the peroxisome where it catalyzes the last step of the beta-oxidation pathway. We have determined the structure of this thiolase in order to study the reaction mechanism, quaternary associations and intracellular targeting of thiolases generally, and to understand the structural basis of genetic disorders associated with human thiolases. RESULTS: Here we report the crystal structure of unliganded yeast thiolase refined at 2.8 A resolution. The enzyme comprises three domains; two compact core domains having the same fold and a loop domain. Each of the two core domains is folded into a mixed five-stranded beta-sheet covered on each side by helices and the two are assembled into a five-layered alpha beta alpha beta alpha structure. The central layer is formed by two helices, which point with their amino termini towards the active site. The loop domain, which is to some extent stabilized by interactions with the other subunit, runs over the surface of the two core domains, encircling the active site of its own subunit. CONCLUSIONS: The crystal structure of thiolase shows that the active site is a shallow pocket, shaped by highly conserved residues. Two conserved cysteines and a histidine at the floor of this pocket probably play key roles in the reaction mechanism. The two active sites are on the same face of the dimer, far from the amino and carboxyl termini of both subunits and the disordered amino-terminal import signal sequence.

Acetyl-CoA C-Acyltransferase↗
PubMed1994

The Aspergillus nidulans CREA protein mediates glucose repression of the ethanol regulon at various levels through competition with the ALCR-specific transactivator.

Carbon catabolite repression in Aspergillus nidulans is mediated by a negative-acting protein coded by the creA gene. We have investigated how CREA controls the expression of the ethanol regulon genes. CREA is a major component of the control of this regulon. Its presence in the cell results in a permanent, albeit partial, repression of the alc genes under all physiological growth conditions, even when the fungus is grown on carbon sources considered to be non-repressing. A crucial step in the control processes is the repression of the positive-acting specific regulatory gene alcR, by the binding of CREA on its cognate target sites on the alcR promoter. The removal of one of these targets, URSA, results in a 50% derepression of the alcR gene. Furthermore, the presence of this sequence contributes directly to the low alcR expression under nonrepressing conditions and reduces alcR promoter function by at least 100-fold. CREA acts both on the regulatory gene alcR and directly on the two structural genes alcA and aldA, as glucose repression of the latter genes occurs in strains where alcR transcription is driven by a strong constitutive and derepressed promoter. In vivo and in vitro competition experiments show that CREA acts by competing directly with the binding of the ALCR activator for the same region of the alcR promoter, a region which encompasses overlapping targets for both regulatory proteins. These data are consistent with a model in which the activating and repressing regulatory proteins compete to regulate expression of the ethanol regulon genes.

Alcohol Dehydrogenase↗
PubMed1994

The crystal structure of human CskSH3: structural diversity near the RT-Src and n-Src loop.

SH3 domains are modules occurring in diverse proteins, ranging from cytoskeletal proteins to signaling proteins, such as tyrosine kinases. The crystal structure of the SH3 domain of Csk (c-Src specific tyrosine kinase) has been refined at a resolution of 2.5 A, with an R-factor of 22.4%. The structure is very similar to the FynSH3 crystal structure. When comparing CskSH3 and FynSH3 it is seen that the structural and charge differences of the RT-Src loop and the n-Src loop, near the conserved Trp47, correlate with different binding properties of these SH3 domains. The structure comparison suggests that those glycines and acid residues which are very well conserved in the SH3 sequences are important for the stability of the SH3 fold.

Amino Acid Sequence↗
PubMed1994

Tropomyosin inhibits the glutaraldehyde-induced cross-link between the central 48-kDa fragment of myosin head and segment 48-67 in actin subdomain 2.

The glutaraldehyde-induced cross-linking of the F-actin-myosin head (S1) complex, previously described [Bertrand et al. (1988) Biochemistry 27, 5728-5736], was investigated in the presence of tropomyosin (Tm) alone or associated with troponin (Tn), at a Tm-Tn/actin/S1 molar ratio of 1:7:3. Among the two acto-S1 cross-linked products with apparent masses of 165 and 200 kDa generated in the absence of the regulatory proteins, only the 165-kDa adduct was formed in the presence of Tm. An identical result was obtained with and without Tn regardless of the presence of Ca2+ and/or Mg(2+)-ADP. The abolition of the 200-kDa cross-linked acto-S1 species was independent of the S1/actin ratio since even a 3-fold excess of S1 over actin, sufficient for fully turning on the thin filament, could not restore the 200-kDa covalent complex. In addition, the acto-S1 contacts cross-linked in either the 165- or 200-kDa product were not involved in the Ca(2+)-linked regulation of the acto-S1 ATPase activity, as the enzymatic activities of both types of complexes were regulated to the same extent by Ca2+/EGTA, in the presence of the regulatory proteins. Cross-linking experiments performed with [14C]glutaraldehyde showed that both covalent complexes were composed of 1 mol of actin bound to 1 mol of S1 heavy chain. The use of proteolytic actin or S1 derivatives together with the direct proteolysis of the acto-S1 covalent adducts revealed that Tm abolished the cross-link between the central 48-kDa fragment of the S1 heavy chain and Lys50 of actin subdomain 2 that is responsible for the formation of the 200-kDa entity, while it did not affect the cross-link between the S1 heavy chain segment of residues 636-642 and Arg28 of actin that generates the 165-kDa derivative. These results provide experimental clues for the interaction of S1 with actin subdomain 2 and show that this contact is implicated in the weak acto-S1 binding state. Furthermore they demonstrate the ability of Tm to affect the structure of actin subdomain 2 even in the presence of S1 bound in the rigor state.

Actins↗
PubMed1994

Identification of insulin-like peptides in cerebral ganglia neurosecretory cells of the mussel Mytilus edulis.

The immunostaining patterns of cerebral ganglia sections from the mussel Mytilus edulis with monoclonal antibodies raised against cerebral ganglia (CG) extracts were compared to those obtained with various polyclonal anti-insulin-like antibodies. One of the monoclonal antibodies (MAB 46) revealed clusters of positive cells in localization comparable to those revealed by the polyclonal antibodies. The nature of the antigen recognized by MAB 46 and the polyclonal antibodies was compared by gel filtration-HPLC of a cerebral ganglia extract. Similar peaks were revealed by the monoclonal and polyclonal antibodies. MAB 46 significantly inhibited the cerebral ganglia induced stimulation of amino-acid incorporation by mantle edge cell suspensions, suggesting that the antigen recognized by MAB 46 is involved in the control of growth.

Animals↗
PubMed1994

Use of monoclonal antibodies for identification of growth-controlling neuropeptides in the mussel Mytilus edulis (Mollusca:Bivalvia).

Monoclonal antibodies were developed against cerebral ganglia (CG) of the mussel Mytilus edulis by the immunization of mice with unpurified homogenates of these organs. The screening protocol of hybridoma was based upon immunohistological observations of cytocentrifugated ganglia cells. A panel of 29 monoclonal antibodies (MABs) specific of CG epitopes was harvested and subsequently used for the immunocytochemical study of CG cells. Several subpopulations of ganglia cells were specifically revealed by MABs. Identification of epitopes involved in growth control was approached via the application of a bioassay allowing the assessment of protein synthesis stimulation. MAB 42 and 46 affected amino acid incorporation induced by CG extract. These results lead to the conclusion that the epitopes recognised by these antibodies are involved in growth control. An immunoenzymatic assay was performed with CG extracts for quantitative analyses of epitopes.

Amino Acids↗
PubMed1994

A gene for Holt-Oram syndrome maps to the distal long arm of chromosome 12.

Holt-Oram syndrome (HOS) is an autosomal dominant condition of unknown origin characterized by congenital septal heart defects with associated malformations of the upper limbs (radial ray). Here, we report on the mapping of a gene causing HOS to the distal long arm of chromosome 12 (12q21-qter) by linkage analysis in nine informative families (Zmax = 6.81 at theta = 0 at the D12S354 locus). Also, multipoint linkage analysis places the HOS gene within the genetic interval between D12S84 and D12S79 (multipoint lod-score in log base 10 = 8.10). The mapping of a gene for HOS is, to our knowledge, the first chromosomal localization of a gene responsible for congenital septal heart defect in human. The characterization of the HOS gene will hopefully shed light on the molecular mechanisms that govern heart septation in the early stages of embryogenesis.

Abnormalities, Multiple↗
PubMed1994

Masculinity, femininity, and marital satisfaction: an examination of theoretical models.

This study sought to investigate the relationship between masculinity, femininity, and marital satisfaction. A number of polynomial multiple regression analyses were performed in an effort to determine the validity of six theoretical models linking sex roles to marital satisfaction. These are the femininity model, masculinity model, sex-typed model, additive androgynous model, interactive androgynous model, and curvilinear model. The sample was composed of 117 couples who completed the Bem Sex-Role Inventory (Bem, 1974) and the Dyadic Adjustment Scale (Spanier, 1976). For men, the results showed that marital satisfaction was related to (a) their self-described levels of femininity and masculinity, (b) the level of self-described femininity of their wives, and (c) the presence of feminine qualities as well as a limited optimal level of masculine qualities which they perceived in their wives. For women, marital satisfaction was associated with (a) the number of self-described feminine qualities and (b) the level of masculinity, as well as an optimal level of femininity, which they perceived in their husbands. Furthermore, small actual-ideal discrepancies in levels of masculinity and femininity ascribed to partners constituted reliable predictors of marital satisfaction for both men and women.

Adult↗
PubMed1994

Mutation analysis in 600 French cystic fibrosis patients.

The cystic fibrosis transmembrane conductance regulator (CFTR) gene of 600 unrelated cystic fibrosis (CF) patients living in France (excluding Brittany) was screened for 105 different mutations. This analysis resulted in the identification of 86% of the CF alleles and complete genotyping of 76% of the patients. The most frequent mutations in this population after delta F508 (69% of the CF chromosomes) are G542X (3.3%), N1303K (1.8%), W1282X (1.5%), 1717-1G-->A (1.3%), 2184delA + 2183 A-->G (0.9%), and R553X (0.8%).

Alleles↗
PubMed1993

Diagnosis of mucopolysaccharidoses in a clinically selected population by urinary glycosaminoglycan analysis: a study of 2,000 urine samples.

Two thousand urine samples (from patients presenting with clinical features suggestive of a mucopolysaccharidosis, MPS) were analysed by a procedure that included a quantitative measurement of glycosaminoglycan (GAG) hexuronic acids (harmine reagent), a qualitative GAG analysis (cellulose acetate electrophoresis) and a study of urinary oligosaccharide patterns. One hundred and seventy MPS and 29 oligosaccharidosis-affected patients were found, but 23 MPS patients among the 170 would have been missed by use of a quantitative procedure only. Fourteen of these (mainly MPS IV A) were detected on the basis of abnormal electrophoresis and the 9 others on the basis of abnormal urinary oligosaccharide patterns (MPS IV B patients). Our results emphasize that normal quantitative GAG excretion alone cannot rule out a diagnosis of MPS; qualitative analysis is also required, as well as oligosaccharide screening.

Adolescent↗
PubMed1993

Very long chain acyl-CoA dehydrogenase deficiency: identification of a new inborn error of mitochondrial fatty acid oxidation in fibroblasts.

A patient highly suspected of long chain fatty acid oxidation defect was investigated for membrane-bound palmitoyl-CoA dehydrogenation in a membrane extract from skin fibroblasts, using 1% sodium cholate as detergent. The profoundly decreased activity observed is consistent with a deficiency of the newly identified mitochondrial 'very long chain acyl-CoA dehydrogenase'.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed1993

FGF3 from Xenopus laevis.

Fibroblast growth factor 3 (FGF3) was first identified as the product of a cellular oncogene activated by mouse mammary tumour virus but its normal role appears to be in the developing embryo. To gain further insights into its function, we have isolated sequences encoding the FGF3 homologue in Xenopus laevis, XFGF3. COS-1 cells transfected with XFGF3 cDNA express a 31 kDa product, p31, generated by signal peptide cleavage and Asn-linked glycosylation at the single consensus site. This product is secreted and becomes associated with the cell surface and extracellular matrix. Proteolytic cleavage of p31 in the extracellular compartment results in an amino-terminally truncated product, p27, that is also glycosylated. Both p31 and p27 bind quantitatively to heparin-Sepharose and can be displaced from the cell surface and extracellular matrix by soluble heparin. Conditioned medium containing these two proteins is capable of inducing transient morphological transformation of NIH3T3 cells and of stimulating DNA synthesis in quiescent C57MG and BALB/MK cells which express different isoforms of FGF receptors 1 and 2. Since XFGF3 behaves very differently from its mouse counterpart, we constructed chimeras in which amino-terminal sequences from XFGF3 were fused with carboxy-terminal sequences from mouse FGF3. Increasing the contribution from mouse FGF3 led to a more restricted host range for the chimeric ligand.

Amino Acid Sequence↗