Biomedical subjects

Christian Wagner

Publications and source records attributed to Christian Wagner.

13 recordsLinked to original sources

PubMed2006

PEDANT genome database: 10 years online.

The PEDANT genome database provides exhaustive annotation of 468 genomes by a broad set of bioinformatics algorithms. We describe recent developments of the PEDANT Web server. The all-new Graphical User Interface (GUI) implemented in Javatrade mark allows for more efficient navigation of the genome data, extended search capabilities, user customization and export facilities. The DNA and Protein viewers have been made highly dynamic and customizable. We also provide Web Services to access the entire body of PEDANT data programmatically. Finally, we report on the application of association rule mining for automatic detection of potential annotation errors. PEDANT is freely accessible to academic users at http://pedant.gsf.de.

Computer Graphics↗

PubMed2006

How to become a uropathogen: comparative genomic analysis of extraintestinal pathogenic Escherichia coli strains.

Uropathogenic Escherichia coli (UPEC) strain 536 (O6:K15:H31) is one of the model organisms of extraintestinal pathogenic E. coli (ExPEC). To analyze this strain's genetic basis of urovirulence, we sequenced the entire genome and compared the data with the genome sequence of UPEC strain CFT073 (O6:K2:H1) and to the available genomes of nonpathogenic E. coli strain MG1655 (K-12) and enterohemorrhagic E. coli. The genome of strain 536 is approximately 292 kb smaller than that of strain CFT073. Genomic differences between both UPEC are mainly restricted to large pathogenicity islands, parts of which are unique to strain 536 or CFT073. Genome comparison underlines that repeated insertions and deletions in certain parts of the genome contribute to genome evolution. Furthermore, 427 and 432 genes are only present in strain 536 or in both UPEC, respectively. The majority of the latter genes is encoded within smaller horizontally acquired DNA regions scattered all over the genome. Several of these genes are involved in increasing the pathogens' fitness and adaptability. Analysis of virulence-associated traits expressed in the two UPEC O6 strains, together with genome comparison, demonstrate the marked genetic and phenotypic variability among UPEC. The ability to accumulate and express a variety of virulence-associated genes distinguishes ExPEC from many commensals and forms the basis for the individual virulence potential of ExPEC. Accordingly, instead of a common virulence mechanism, different ways exist among ExPEC to cause disease.

Biological Evolution↗

PubMed2005

Nano-sizing of specific gene domains in intact human cell nuclei by spatially modulated illumination light microscopy.

Although light microscopy and three-dimensional image analysis have made considerable progress during the last decade, it is still challenging to analyze the genome nano-architecture of specific gene domains in three-dimensional cell nuclei by fluorescence microscopy. Here, we present for the first time chromatin compaction measurements in human lymphocyte cell nuclei for three different, specific gene domains using a novel light microscopic approach called Spatially Modulated Illumination microscopy. Gene domains for p53, p58, and c-myc were labeled by fluorescence in situ hybridization and the sizes of the fluorescence in situ hybridization "spots" were measured. The mean diameters of the gene domains were determined to 103 nm (c-myc), 119 nm (p53), and 123 nm (p58) and did not correlate to the genomic, labeled sequence length. Assuming a spherical domain shape, these values would correspond to volumes of 5.7 x 10(-4) microm(3) (c-myc), 8.9 x 10(-4) microm(3) (p53), and 9.7 x 10(-4) microm(3) (p58). These volumes are approximately 2 orders of magnitude smaller than the diffraction limited illumination or observation volume, respectively, in a confocal laser scanning microscope using a high numerical aperture objective lens. By comparison of the labeled sequence length to the domain size, compaction ratios were estimated to 1:129 (p53), 1:235 (p58), and 1:396 (c-myc). The measurements demonstrate the advantage of the SMI technique for the analysis of gene domain nano-architecture in cell nuclei. The data indicate that chromatin compaction is subjected to a large variability which may be due to different states of genetic activity or reflect the cell cycle state.

Biophysical Phenomena↗

PubMed2005

The PEDANT genome database in 2005.

The PEDANT genome database (http://pedant.gsf.de) contains pre-computed bioinformatics analyses of publicly available genomes. Its main mission is to provide robust automatic annotation of the vast majority of amino acid sequences, which have not been subjected to in-depth manual curation by human experts in high-quality protein sequence databases. By design PEDANT annotation is genome-oriented, making it possible to explore genomic context of gene products, and evaluate functional and structural content of genomes using a category-based query mechanism. At present, the PEDANT database contains exhaustive annotation of over 1,240,000 proteins from 270 eubacterial, 23 archeal and 41 eukaryotic genomes.

Computational Biology↗

PubMed2005

Novel approach to mapping of resistance mutations in whole genomes by using restriction enzyme modulation of transformation efficiency.

Restriction enzyme modulation of transformation efficiencies (REMOTE) is a method that makes use of genome restriction maps and experimentally observed differences in transformation efficiencies of genomic DNA restriction digests to discover the location of mutations in genomes. The frequency with which digested genomic DNA from a resistant strain transforms a susceptible strain to resistance is primarily determined by the size of the fragment containing the resistance mutation and the distance of the mutation to the end of the fragment. The positions of restriction enzyme cleavage sites immediately flanking the resistance mutation define these parameters. The mapping procedure involves a process of elimination in which digests that transform with high frequency indicate that the restriction enzyme cleavage sites are relatively far away from the mutation, while digests that transform with low frequency indicate that the sites are close to the mutation. The transformation data are compared computationally to the genome restriction map to identify the regions that best fit the data. Transformations with PCR amplicons encompassing candidate regions identify the resistance locus and enable identification of the mutation. REMOTE was developed using Haemophilus influenzae strains with mutations in gyrA, gyrB, and rpsE that confer resistance to ciprofloxacin, novobiocin, and spectinomycin, respectively. We applied REMOTE to identify mutations that confer resistance to two novel antibacterial compounds. The resistance mutations were found in genes that can decrease the intracellular concentration of compounds: acrB, which encodes a subunit of the AcrAB-TolC efflux pump; and fadL, which encodes a long-chain fatty acid transporter.

Anti-Bacterial Agents↗

PubMed2003

Negative regulation of phospholipid biosynthesis in Saccharomyces cerevisiae by a Candida albicans orthologue of OPI1.

Structural genes of phospholipid biosynthesis in the yeast Saccharomyces cerevisiae are coordinately regulated by a UAS element, designated ICRE (inositol/choline-responsive element). Opi1 is a negative regulator responsible for repression of ICRE-dependent genes in the presence of an excess of inositol and choline. Gene regulation by phospholipid precursors has been also reported for the pathogenic yeast Candida albicans. Screening of a data base containing raw sequences of the C. albicans genome project allowed us to identify an open reading frame exhibiting weak similarity to Opi1. Expression of the putative CaOPI1 in an opi1 mutant of S. cerevisiae could restore repression of an ICRE-dependent reporter gene. Similar to OPI1, overexpression of CaOPI1 strongly inhibited derepression of ICRE-driven genes leading to inositol-requiring transformants. Previous work has shown that Opi1 mediates gene repression by interaction with the pleiotropic repressor Sin3. The genome of C. albicans also encodes a protein similar to Sin3 (CaSin3). By two-hybrid analyses and in vitro studies for protein-protein interaction we were able to show that CaOpi1 binds to ScSin3. ScOpi1 could also interact with CaSin3, while CaOpi1 failed to bind to CaSin3. Despite of some conservation of regulatory mechanisms between both yeasts, these results suggest that repression of phospholipid biosynthetic genes in C. albicans is mediated by a mechanism which does not involve recruitment of CaSin3 by CaOpi1.

Amino Acid Sequence↗

PubMed2003

Experimental evidence for an intrinsic route to polymer melt fracture phenomena: a nonlinear instability of viscoelastic Poiseuille flow.

The production rate of polymer fibers by extrusion is usually limited by the appearance of a series of instabilities ("melt fracture") that lead to unwanted undulations of the surface. We present both qualitative and quantitative experimental evidence that-in addition to previously known polymer-specific scenarios-there is an intrinsic route towards melt fracture type phenomena: a nonlinear ("subcritical") instability of viscoelastic Poiseuille flow.

Journal Article↗

PubMed2003

Intrinsic route to melt fracture in polymer extrusion: a weakly nonlinear subcritical instability of viscoelastic poiseuille flow.

As is well known, the extrusion rate of polymers from a cylindrical tube or slit (a "die") is in practice limited by the appearance of "melt fracture" instabilities which give rise to unwanted distortions or even fracture of the extrudate. We present the results of a weakly nonlinear analysis which gives evidence for an intrinsic generic route to melt fracture via a weakly nonlinear subcritical instability of viscoelastic Poiseuille flow. This instability and the onset of associated melt fracture phenomena appear at a well-defined ratio of the elastic stresses to viscous stresses of the polymer solution.

Journal Article↗

PubMed2003

The PEDANT genome database.

The PEDANT genome database (http://pedant.gsf.de) provides exhaustive automatic analysis of genomic sequences by a large variety of established bioinformatics tools through a comprehensive Web-based user interface. One hundred and seventy seven completely sequenced and unfinished genomes have been processed so far, including large eukaryotic genomes (mouse, human) published recently. In this contribution, we describe the current status of the PEDANT database and novel analytical features added to the PEDANT server in 2002. Those include: (i) integration with the BioRS data retrieval system which allows fast text queries, (ii) pre-computed sequence clusters in each complete genome, (iii) a comprehensive set of tools for genome comparison, including genome comparison tables and protein function prediction based on genomic context, and (iv) computation and visualization of protein-protein interaction (PPI) networks based on experimental data. The availability of functional and structural predictions for 650 000 genomic proteins in well organized form makes PEDANT a useful resource for both functional and structural genomics.

Animals↗

PubMed2003

The Hansenula polymorpha (strain CBS4732) genome sequencing and analysis.

The methylotrophic yeast Hansenula polymorpha is a recognised model system for investigation of peroxisomal function, special metabolic pathways like methanol metabolism, of nitrate assimilation or thermostability. Strain RB11, an odc1 derivative of the particular H. polymorpha isolate CBS4732 (synonymous to ATCC34438, NRRL-Y-5445, CCY38-22-2) has been developed as a platform for heterologous gene expression. The scientific and industrial significance of this organism is now being met by the characterisation of its entire genome. The H. polymorpha RB11 genome consists of approximately 9.5 Mb and is organised as six chromosomes ranging in size from 0.9 to 2.2 Mb. Over 90% of the genome was sequenced with concomitant high accuracy and assembled into 48 contigs organised on eight scaffolds (supercontigs). After manual annotation 4767 out of 5933 open reading frames (ORFs) with significant homologies to a non-redundant protein database were predicted. The remaining 1166 ORFs showed no significant similarity to known proteins. The number of ORFs is comparable to that of other sequenced budding yeasts of similar genome size.

Base Sequence↗

PubMed2003

Discrimination of benign common nevi from malignant melanoma lesions by use of features based on spectral properties of the wavelet transform.

OBJECTIVE: To evaluate the possibilities of describing and discriminating common nevi and malignant melanoma tissue with features based on spectral properties of the Daubechies 4 wavelet transform. STUDY DESIGN: Images of common nevi and malignant melanoma were dissected in square elements. The wavelet coefficients were calculated inside the square elements. The diagonal coefficients and related power spectra were used for further analysis. The analysis results served as guide for the selection of features, including standard deviations of wavelet coefficients inside the frequency bands and the energy of the frequency bands. These features describe properties of the frequency bands, representing information on different scales. To test the usefulness of the features for discrimination, a study set of 80 cases was classified by classification and regression trees analysis. The set was divided into a training set and a test set. RESULTS: In the case of benign common nevi, the energies of the lower frequency bands and higher, whereas malignant melanoma tissue shows more variability of the coefficients in higher-frequency bands. The influence on the detail properties of the images was studied by suppression of coefficients with low values, which are concentrated mainly in higher-frequency bands. In the case of benign common nevi the main information is contained in 15% of the coefficients and in the case of malignant melanoma, in 39%. The results of classification show a clear-cut difference between the cases. The classification correctly classified 95.78% of nevi elements and 94.22% of melanoma elements in the training set and 100% of cases of benign nevi and 80% of cases of malignant melanoma in the test set. CONCLUSION: Features based on the wavelet power spectrum contain sufficient information for differentiation between common nevi and malignant melanomas.

Artificial Intelligence↗

PubMed2002

Genetic analysis and functional characterization of the Streptococcus pneumoniae vic operon.

The vic two-component signal transduction system of Streptococcus pneumoniae is essential for growth. The vic operon comprises three genes encoding the following: VicR, a response regulator of the OmpR family; VicK, its cognate histidine kinase; and VicX, a putative protein sharing 55% identity to the predicted product (YycJ) of an open reading frame in the Bacillus subtilis genome. We show that not only is vic essential for viability but it also influences virulence and competence. A putative transcriptional start site for the vic operon was mapped 16 bp upstream of the ATG codon of vicR. Only one transcript of 2.9 kb, encoding all three genes, was detected by Northern blot analysis. VicK, an atypical PAS domain-containing histidine kinase, can be autophosphorylated in vitro, and VicR functions in vitro as a phospho-acceptor protein. (PAS is an acronym formed from the names of the proteins in which the domains were first recognized: the Drosophila period clock protein [PER], vertebrate aryl hydrocarbon receptor nuclear translocator [ARNT], and Drosophila single-minded protein [SIM].) PAS domains are commonly involved in sensing intracellular signals such as redox potential, which suggests that the signal for vic might also originate in the cytoplasm. Growth rate, competence, and virulence were monitored in strains with mutations in the vic operon. Overexpression of the histidine kinase, VicK, resulted in decreased virulence, whereas the transformability of a null mutant decreased by 3 orders of magnitude.

Animals↗

PubMedDate not supplied

Impact of pneumococcal vaccination on morbidity and mortality of geriatric patients: a case-controlled study.

BACKGROUND: Infections due to Streptococcus pneumoniae are the major cause of adult community-acquired pneumonia, especially in elderly persons with chronic medical conditions. Despite their well-documented efficacy against bacteraemic disease and deaths in the elderly population, pneumococcal polysaccharide vaccines are still very much underused. OBJECTIVE: A retrospective, case-controlled study was performed to investigate the impact of vaccination with a polysaccharide pneumococcal vaccine, together with other risk factors, on the incidence of pneumonia and deaths in patients in a long-stay geriatric hospital. METHODS: Subjects were 1,077 residents in a long-stay geriatric hospital in Vienna, Austria, including 359 patients diagnosed as having pneumonia during the period from July 1996 to October 1998 and 718 control subjects. Two controls resident in the hospital during the same time period were matched for each case according to demographic characteristics, chronic illness, and duration of stay in the geriatric ward. The vaccination status was established for all subjects. A logistic regression analysis was performed to assess the efficacy of vaccination and the impact of other cofactors on disease and death. RESULTS: In cases and controls, 514 (47.7%) had received a pneumococcal vaccine within 2 years prior to the study. There were no differences in demographic characteristics, underlying medical conditions, or duration of stay in the hospital between vaccinated and non-vaccinated patients. In patients diagnosed with pneumonia, 66% were unvaccinated. Logistic regression analysis showed that vaccination significantly decreased the risk of pneumonia (odds ratio 0.279; p < 0.0001). Of the cofactors tested, only gender (lower risk in males) and diabetes mellitus (higher risk) had any impact on disease risk and vaccine efficacy. There appeared to be a highly significant effect of vaccination, reducing the risk of all deaths (odds ratio 0.269; p < 0.0001) and deaths due to pneumonia (odds ratio 0.331; p < 0.0001). CONCLUSION: This study showed that vaccination with a polysaccharide pneumococcal vaccine is effective in all groups of geriatric subjects and has a consequential value for health and well-being of elderly institutionalized patients.

Aged↗