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Biomedical subjects

P Bucher

Publications and source records attributed to P Bucher.

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

[New possibilities for reconstructing extensive jaw defects with prefabricated microvascular fibula transplants and ITI implants].

The reconstruction of extensive jaw defects is frequently only possible with microvascular bone flaps. Here we are presenting an operative technique using prefabricated fibular flaps and osseointegrated implants. In a first operation, the fibula is prepared with implants, split skin graft, and a nonresorbable membrane. The jaw defect is reconstructed 6 weeks later and can be treated directly with a prosthesis thanks to osseointegrated implants. The technique is described with reference to 5 patients already operated according to this technique and the initial findings are evaluated.

Adult↗
PubMed2000

InterPro--an integrated documentation resource for protein families, domains and functional sites.

MOTIVATION: InterPro is a new integrated documentation resource for protein families, domains and functional sites, developed initially as a means of rationalising the complementary efforts of the PROSITE, PRINTS, Pfam and ProDom database projects. RESULTS: Merged annotations from PRINTS, PROSITE and Pfam form the InterPro core. Each combined InterPro entry includes functional descriptions and literature references, and links are made back to the relevant parent database(s), allowing users to see at a glance whether a particular family or domain has associated patterns, profiles, fingerprints, etc. Merged and individual entries (i.e. those that have no counterpart in the companion resources) are assigned unique accession numbers. Release 1.2 of InterPro (June 2000) contains over 3000 entries, representing families, domains, repeats and sites of post-translational modification (PTMs) encoded by 6581 different regular expressions, profiles, fingerprints and Hidden Markov Models (HMMs). Each InterPro entry lists all the matches against SWISS-PROT and TrEMBL (more than 1000000 hits from 264333 different proteins out of 384572 in SWISS-PROT and TrEMBL).

Computational Biology↗
PubMed1999

The PROSITE database, its status in 1999.

The PROSITE database (http://www.expasy.ch/sprot/prosite.htm l) consists of biologically significant patterns and profiles formulated in such a way that with appropriate computational tools it can help to determine to which known family of protein (if any) a new sequence belongs, or which known domain(s) it contains.

Binding Sites↗
PubMed1999

The Eukaryotic Promoter Database (EPD): recent developments.

The Eukaryotic Promoter Database (EPD) is an annotated non-redundant collection of eukaryotic POL II promoters, for which the transcription start site has been determined experimentally. Access to promoter sequences is provided by pointers to positions in nucleotide sequence entries. The annotation part of an entry includes description of the initiation site mapping data, cross-references to other databases, and bibliographic references. EPD is structured in a way that facilitates dynamic extraction of biologically meaningful promoter subsets for comparative sequence analysis. Recent efforts have focused on exhaustive cross-referencing to the EMBL nucleotide sequence database, and on the improvement of the WWW-based user interfaces and data retrieval mechanisms. EPD can be accessed at http://www.epd.isb-sib.ch

Algorithms↗
PubMed1999

A quantitative, single-cell PCR analysis of an antigen-specific TCR repertoire selected during an in vivo CD8 response: direct evidence for a wide range of clone sizes with uniform tissue distribution.

The development of T cell effector and memory responses against foreign antigens (Ags) involves the activation, differentiation and proliferation of naive T cells expressing distinct Ag-specific TCRs. Understanding the complexity of Ag-selected TCR repertoires in individual responders in terms of the sequences selected and their relative frequencies may provide indications about how a repertoire is established and suggest ways to influence the outcome of an immune response. Most methods of repertoire analysis are unsuitable for calculating the relative in vivo frequencies of Ag-specific clones (expressing distinct TCRs) selected during an immune response, whereas sequence data obtained by single-cell PCR analysis directly reflect cell frequencies if a sufficiently large number of cells is sampled. Using a CD8 T cell response in normal mice in which Ag-selected cells are identified by cell surface phenotype and rearranged TCRBV sequences are determined by PCR amplification of genomic DNA directly from single cells, we have analyzed a large number (>200 per animal) of structurally-related Ag-specific TCRs to calculate the frequencies of distinct TCRs selected by individual mice. We found that each responder selects a unique Ag-specific TCR repertoire in which the various TCRBV sequences are present in a wide range of frequencies. However, the overall distribution of sequences is quite similar for different responder animals. Moreover, an individual's selected TCR repertoire is uniformly represented among Ag-specific CD8 cells circulating in the blood or localized in the spleen or liver. Relatively few sequences make up the bulk of the repertoire and account for the oligoclonality observed in earlier studies. We discuss various models that could account for this skewed distribution of an Ag-selected TCR repertoire.

Animals↗
PubMed1999

Regulatory elements and expression profiles.

There has been steady progress in the computational analysis of transcription control regions, but current methods of predicting the gene regulatory features of noncoding sequences are still not accurate enough to be useful in automatic genome annotation. Therefore, detailed information on the expression patterns of newly sequenced genes is more likely to come from microarray-based high-throughput mRNA quantitation technologies, which have made revolutionary progress over the past few years and are now ready for genome-wide application. Future solutions to the regulatory element prediction problem may be found by the combined analysis of genome sequence and expression data.

Animals↗
PubMed1999

Suppression of growth hormone by oral glucose in the evaluation of tall stature.

Excess secretion of growth hormone is a rare diagnosis in children or adolescents with tall stature. An oral glucose tolerance test (OGT) with determination of growth hormone is generally recommended to exclude this disorder. In order to test the validity of this approach in pediatric subjects, OGT tests were performed in 126 tall subjects (age: 12.4 +/- 1.8 years; height: 3.1 +/- 0.8 SDS). Nonsuppression was present in 39 subjects, however, anthropometric analysis and follow-up excluded the diagnosis of eosinophilic pituitary adenoma in all patients. The lowest GH concentration was reached 90 min after ingestion of oral glucose, GH rose above baseline at 180 min. Plasma concentrations of glucose and insulin did not differ between suppressors and nonsuppressors. In conclusion, absent suppression of growth hormone by oral glucose is common in tall children and adolescents. The test is therefore not recommended as a general screening for excess growth hormone. Prolonging the test beyond 120 min does not increase the diagnostic value.

Adolescent↗
PubMed1999

ESTScan: a program for detecting, evaluating, and reconstructing potential coding regions in EST sequences.

One of the problems associated with the large-scale analysis of unannotated, low quality EST sequences is the detection of coding regions and the correction of frameshift errors that they often contain. We introduce a new type of hidden Markov model that explicitly deals with the possibility of errors in the sequence to analyze, and incorporates a method for correcting these errors. This model was implemented in an efficient and robust program, ESTScan. We show that ESTScan can detect and extract coding regions from low-quality sequences with high selectivity and sensitivity, and is able to accurately correct frameshift errors. In the framework of genome sequencing projects, ESTScan could become a very useful tool for gene discovery, for quality control, and for the assembly of contigs representing the coding regions of genes.

Algorithms↗
PubMed1998

A model of Cdc25 phosphatase catalytic domain and Cdk-interaction surface based on the presence of a rhodanese homology domain.

Mammalian Cdc25 phosphatase is responsible for the dephosphorylation of Cdc2 and other cyclin-dependent kinases at Thr14 and Tyr15, thus activating the kinase and allowing cell cycle progression. The catalytic domain of this dual-specificity phosphatase has recently been mapped to the 180 most C-terminal amino acids. Apart from a CX3R motif, which is present at the active site of all known tyrosine phosphatases, Cdc25 does not share any obvious sequence similarity with any of those enzymes. Until very recently, the Cdc25 family was the only subfamily of tyrosine phosphates for which no three-dimensional structural data were available. Using the generalized profile technique, a sensitive method for sequence database searches, we found an extended and highly significant sequence similarity between the Cdc25 catalytic domain and similarly sized regions in other proteins: the non-catalytic domain of two distinct families of MAP-kinase phosphates, the non-catalytic domain of several ubiquitin protein hydrolases, the N and C-terminal domain of rhodanese, and a large and heterogeneous groups of stress-response proteins from all phyla. The relationship of Cdc25 to the structurally well-characterized rhodanese spans the entire catalytic domain and served as template for a structural model for human Cdc25a, which is fundamentally different from previously suggested models for Cdc25 catalytic domain organization. The surface positioning of subfamily-specific conserved residues allows us to predict the sites of interaction with Cdk2, a physiological target of Cdc25a. Based on the results of this analysis, we also predict that the budding yeast arsenate resistance protein Acr2 and the ORF Ygr203w encode protein phosphatases with catalytic properties similar to that of the Cdc25 family. Recent determination of the crystal structure of the Cdc25a catalytic domain supports the validity of the model and demonstrates the power of the generalized sequence profile technique in homology-based modeling of the three-dimensional structure of a protein having a weak but significant sequence similarity with a structurally characterized protein.

Amino Acid Sequence↗
PubMed1998

The Eukaryotic Promoter Database EPD.

The Eukaryotic Promoter Database (EPD) is an annotated non-redundant collection of experimentally characterised eukaryotic POL II promoters. The underlying definition of a promoter is that of a transcription initiation site. All information presented in EPD results from an independent evaluation of primary experimental data shown in the biological literature. Sequences flanking transcription initiation sites are indirectly given by pointers to EMBL sequences. The annotation part of a promoter entry includes description of the promoter-defining evidence, cross-references to other databases, and bibliographic references. Being designed as a resource for comparative sequence analysis, EPD is structured in a way that facilitates dynamic extraction of biologically meaningful promoter subsets. The database is available through the World Wide Web at URL http://cmpteam4.unil.ch

Animals↗
PubMed1998

The discoidin domain family revisited: new members from prokaryotes and a homology-based fold prediction.

Members of the discoidin (DS) domain family, which includes the C1 and C2 repeats of blood coagulation factors V and VIII, occur in a great variety of eukaryotic proteins, most of which have been implicated in cell-adhesion or developmental processes. So far, no three-dimensional structure of a known example of this extracellular module has been determined, limiting the usefulness of identifying a new sequence as member of this family. Here, we present results of a recent search of the protein sequence database for new DS domains using generalized profiles, a sensitive multiple alignment-based search technique. Several previously unrecognized DS domains could be identified by this method, including the first examples from prokaryotic species. More importantly, we present statistical, structural, and functional evidence that the D1 domain of galactose oxidase whose three-dimensional structure has been determined at 1.7 A resolution, is a distant member of this family. Taken together, these findings significantly expand the concept of the DS domain, by extending its taxonomic range and by implying a fold prediction for all its members. The proposed alignment with the galactose oxidase sequence makes it possible to construct homology-based three-dimensional models for the most interesting examples, as illustrated by an accompanying paper on the C1 and C2 domains of factor V.

Amino Acid Sequence↗
PubMed1998

SEView: a Java applet for browsing molecular sequence data.

SEView is a Java applet that represents known or predicted elements of a protein or nucleotide sequence. It replaces or supplements the textual format of databases or program output with an interactive, graphical representation that is easily available through a WWW browser. Independence from the source data's format is achieved through a description language and ad hoc translators, which make the system versatile and flexible.

Computer Graphics↗
PubMed1997

A conserved domain is present in different families of vesicular fusion proteins: a new superfamily.

We have analyzed conserved domains in t-SNAREs [soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptors in the target membrane], proteins that are believed to be involved in the fusion of transport vesicles with their target membrane. By using a sensitive computer method, the generalized profile method, we were able to identify a new homology domain that is common in the two protein families previously identified to act as t-SNAREs, the syntaxin and SNAP-25 (synaptosome-associated protein of 25 kDa) families, which therefore constitute a new superfamily. This homology domain of approximately 60 amino acids is predicted to form a coiled-coil structure. The significance of this homology domain could be demonstrated by a partial suppression of the coiled-coil properties of the domain profile. In proteins belonging to the syntaxin family, a single homology domain is located near the transmembrane domain, whereas the members of the SNAP-25 family possess two homology domains. This domain was also identified in several proteins that have been implicated in vesicular transport but do not belong to any of the t-SNARE protein families. Several new yeast, nematode, and mammalian proteins were identified that belong to the new superfamily. The evolutionary conservation of the SNARE coiled-coil homology domain suggests that this domain has a similar function in different membrane fusion proteins.

Amino Acid Sequence↗
PubMed1997

The PROSITE database, its status in 1997.

The PROSITE database consists of biologically significant patterns and profiles formulated in such a way that with appropriate computational tools it can help to determine to which known family of protein (if any) a new sequence belongs, or which known domain(s) it contains.

Amino Acid Sequence↗
PubMed1997

A conserved IL-2 responsive enhancer in the IL-2R alpha gene.

IL-2 stimulates expression of the alpha subunit of the high affinity IL-2 receptor (IL-2R alpha) in antigen-activated T lymphocytes, by increasing IL-2R alpha gene transcription. This response is mediated by a 52 nt IL-2 responsive enhancer (IL-2rE) that is conserved between mouse and man. The mouse enhancer is 1.3 kb upstream of the transcription start site and co-localizes with an inducible DNasel hypersensitive site, whereas the human homologue maps to -4 kb. The human IL-2rE is functional in rodent cells. Both enhancers contain two potential STAT binding sites and an Ets consensus motif. One of the STAT motifs overlaps with a binding site for GATA factors. Functional analysis of the mouse and human enhancers indicates that IL-2-activated STAT5 and the constitutively active Ets protein Elf-1 play a predominant role in controlling IL-2rE activity.

Animals↗