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Biomedical subjects

F Götz

Publications and source records attributed to F Götz.

At least 19 recordsLinked to original sources
PubMed2006

eLearning in education and advanced training in neuroradiology: introduction of a web-based teaching and learning application.

INTRODUCTION: New information technologies offer the possibility of major improvements in the professional education and advanced training of physicians. The web-based, multimedia teaching and learning application Schoolbook has been created and utilized for neuroradiology. METHODS: Schoolbook is technically based as a content management system and is realized in a LAMP environment. The content is generated with the help of the developed system and stored in a database. The layout is defined by a PHP application, and the webpages are generated from the system. RESULTS: Schoolbook is realized as an authoring tool so that it can be integrated into daily practice. This enables the teacher to autonomously process the content into the web-based application which is used for lectures, seminars and self-study. A multimedia case library is the central building block of Schoolbook for neuroradiology, whereby the learner is provided with original diagnostic and therapeutic data from numerous individual cases. The user can put individual emphasis on key learning points as there are various ways to work with the case histories. Besides the case-based way of teaching and learning, a systematically structured way of dealing with the content is available. CONCLUSION: eLearning offers various opportunities for teaching and learning in academic and scientific as well as in economic contexts. Web-based applications such as Schoolbook may be beneficial not only for basic university education but also for the realization of international educational programmes such as the European Master of Medical Science with a major in neuroradiology.

Computer-Assisted Instruction↗
PubMed2006

Naturally processed dermcidin-derived peptides do not permeabilize bacterial membranes and kill microorganisms irrespective of their charge.

Dermcidin (DCD) is a recently described antimicrobial peptide, which is constitutively expressed in eccrine sweat glands and transported via sweat to the epidermal surface. By postsecretory proteolytic processing in sweat the dermcidin protein gives rise to several truncated DCD peptides which differ in length and net charge. In order to understand the mechanism of antimicrobial activity, we analyzed the spectrum of activity of several naturally processed dermcidin-derived peptides, the secondary structure in different solvents, and the ability of these peptides to interact with or permeabilize the bacterial membrane. Interestingly, although all naturally processed DCD peptides can adopt an alpha-helical conformation in solvents, they have a diverse and partially overlapping spectrum of activity against gram-positive and gram-negative bacteria. This indicates that the net charge and the secondary structure of the peptides are not important for the toxic activity. Furthermore, using carboxyfluorescein-loaded liposomes, membrane permeability studies and electron microscopy we investigated whether DCD peptides are able to permeabilize bacterial membranes. The data convincingly show that irrespective of charge the different DCD peptides are not able to permeabilize bacterial membranes. However, bacterial mutants lacking specific cell envelope modifications exhibited different susceptibilities to killing by DCD peptides than wild-type bacterial strains. Finally, immunoelectron microscopy studies indicated that DCD peptides are able to bind to the bacterial surface; however, signs of membrane perturbation were not observed. These studies indicate that DCD peptides do not exert their activity by permeabilizing bacterial membranes.

Amino Acid Sequence↗
PubMed2004

ParSeq: searching motifs with structural and biochemical properties.

SUMMARY: Searches for variable motifs such as protein-binding sites or promoter regions are more complex than the search for casual motifs. For example, in amino acid sequences comparing motifs alone mostly proves to be insufficient to detect regions that represent proteins with a special function, because the function depends on biochemical properties of individual amino acids (such as polarity or hydrophobicity). Pure string matching programs are not able to find these motifs; hence, we developed ParSeq, a program that combines the search for motifs with certain structural properties, the verification of biochemical properties, an approximate search mechanism and a stepwise creation of the motif description by allowing to search on previously obtained results. AVAILABILITY: http://www-pr.informatik.uni-tuebingen.de/parseq

Algorithms↗
PubMed2002

The nitrate reductase and nitrite reductase operons and the narT gene of Staphylococcus carnosus are positively controlled by the novel two-component system NreBC.

In Staphylococcus carnosus, the nreABC (for nitrogen regulation) genes were identified and shown to link the nitrate reductase operon (narGHJI) and the putative nitrate transporter gene narT. An nreABC deletion mutant, m1, was dramatically affected in nitrate and nitrite reduction and growth. Transcription of narT, narGHJI, and the nitrite reductase (nir) operon was severely reduced even when cells were cultivated anaerobically without nitrate or nitrite. nreABC transcripts were detected when cells were grown aerobically or anaerobically with or without nitrate or nitrite. NreA is a GAF domain-containing protein of unknown function. In vivo and in vitro studies showed that NreC is phosphorylated by NreB and that phospho-NreC specifically binds to a GC-rich palindromic sequence to enhance transcription initiation. This binding motif was found at the narGHJI, nir, and narT promoters but not at the moeB promoter. NreB is a cytosolic protein with four N-terminal cysteine residues. The second cysteine residue was shown to be important for NreB function. In vitro autophosphorylation of NreB was not affected by nitrate, nitrite, or molybdate. The nir promoter activity was iron dependent. The data provide evidence for a global regulatory system important for aerobic and anaerobic metabolism, with NreB and NreC forming a classical two-component system and NreB acting as a sensor protein with oxygen as the effector molecule.

Bacterial Proteins↗
PubMed2001

Characterization of the importance of Staphylococcus epidermidis autolysin and polysaccharide intercellular adhesin in the pathogenesis of intravascular catheter-associated infection in a rat model.

A rat central venous catheter (CVC) infection model was used to assess the importance of the proteinacious autolysin (AtlE) and the polysaccharide intercellular adhesin (PIA) in the pathogenesis of Staphylococcus epidermidis CVC-associated infection. Wild-type (wt) S. epidermidis O-47 was significantly more likely to cause a CVC infection than was either of the isogenic mutant strains (AtlE-negative [O-47mut1] or PIA-negative [O-47mut2]). Bacteria were retrieved from the explanted catheters of 87.5% of rats inoculated with S. epidermidis O-47, compared with 25% of rats challenged with either S. epidermidis O-47mut1 or O-47mut2 (P=.007). Peripheral bacteremia was documented in 75% of rats challenged with S. epidermidis O-47, compared with 12.5% and 25% challenged with O-47mut1 and O-47mut2, respectively (P=.009). Metastatic disease was more common in rats inoculated with wt S. epidermidis, compared with AtlE- or PIA-deficient mutants. These results confirm the importance of initial adherence, associated with AtlE, and biofilm production, mediated by PIA, in the pathogenesis of S. epidermidis experimental CVC infection.

Animals↗
PubMed2001

Cloning, purification and characterisation of Staphylococcus warneri lipase 2.

A gene encoding an extracellular lipase was identified in Staphylococcus warneri 863. The deduced lipase is organised as a prepro-protein and has significant similarity to other staphylococcal lipases. The mature part of the lipase was expressed with an N-terminal histidine tag in Escherichia coli, purified and biochemically characterised. The results show that the purified lipase (named SWL2) combines the properties of the staphylococcal lipases characterised so far. It has both a high preference for short chain substrates and surprisingly, it also displays phospholipase activity. Homology alignment was used to analyse sequence-function relationships of the staphylococcal lipase family with the aim to identify the structural basis underlying the different properties of the staphylococcal lipases.

Amino Acid Sequence↗
PubMed2001

Structure-function relationships in the tryptophan-rich, antimicrobial peptide indolicidin.

Indolicidin is a cationic 13 amino acid peptide amide produced in the granules of bovine neutrophils with the sequence H-ILPWKWPWWPWRR-NH2. Indolicidin is both antimicrobial and, to a lesser extent, haemolytic. In order to systematically investigate structure-function relationships, the solid-phase synthesis of indolicidin and 48 distinct analogues are reported, as well as the characterization of their respective biological properties. Peptides synthesized and characterized include analogues with modified terminal functions, truncations from either terminus, an alanine scan to determine the role of each individual amino acid, specific amino acid exchanges of aromatic, charged and structural residues and several retro-, inverso- and retroinverso-analogues. Together, characterization of these analogues identifies specific residues involved in antimicrobial or haemolytic activity and suggests a core structure that may form a scaffold for the further development of peptidomimetic analogues of indolicidin.

Amino Acid Sequence↗
PubMed2001

Secretion of human growth hormone by the food-grade bacterium Staphylococcus carnosus requires a propeptide irrespective of the signal peptide used.

Staphylococcal exoproteins can be divided into two groups. One group comprises proteins bearing only a signal peptide, the other group requires an additional propeptide for secretion. The secretion signals of the propeptide-requiring lipase from Staphylococcus hyicus (Lip) have been frequently used to produce recombinant secretory proteins in the food-grade species Staphylococcus carnosus. However, it has been unclear whether recombinant proteins can be secreted using signal peptides of staphylococcal proteins without propeptide. The human growth hormone protein (hGH) was fused to various staphylococcal secretion signals of proteins without propeptide (Seb, SceA, and SceB) and of proteins requiring a propeptide (lipase, lysostaphin, and glycerol ester hydrolase). Secretory hGH was efficiently produced by S. carnosus after fusion with any propeptide-containing secretion signal, whereas precursor proteins were retained in the cells when only a signal peptide was used. Addition of the first six amino acid residues of mature SceA to the signal peptide did also not lead to secretion of hGH. It was concluded that the properties of the mature protein domains determine whether a propeptide is required for secretion or not. The Lip propeptide could be efficiently removed from hGH after introduction of an enterokinase cleavage site between the two protein domains.

Amino Acid Sequence↗
PubMed2001

Dual role of GdmH in producer immunity and secretion of the Staphylococcal lantibiotics gallidermin and epidermin.

The biosynthetic gene clusters of the staphylococcal lantibiotics epidermin and gallidermin are distinguished by the presence of the unique genes epiH and gdmH, respectively. They encode accessory factors for the ATP-binding cassette transporters that mediate secretion of the antimicrobial peptides. Here, we show that gdmH also contributes to immunity to gallidermin but not to nisin. gdmH alone affected susceptibility to gallidermin only moderately, but it led to a multiplication of the immunity level mediated by the FEG immunity genes when cloned together with the gdmT gene, suggesting a synergistic activity of the H and FEG systems. gdmH-related genes were identified in the genomes of several bacteria, indicating an involvement in further cellular functions.

Amino Acid Sequence↗
PubMed2001

Secretion of active recombinant human tissue plasminogen activator derivatives in Escherichia coli.

The DNA fragment coding for kringle 2 plus serine protease domains (K2S) of tissue plasminogen activator (tPA) was inserted into a phagemid vector, pComb3HSS. In the recombinant vector, pComb3H-K2S, the K2S gene was fused to gpIII of PhiM13 and linked to the OmpA signal sequence. The resulting gene, rK2S-gpIII, was inducibly expressed in Escherichia coli XL-1 Blue. The protein was presented on the phage particle. To stop the expression of gpIII, a stop codon between K2S and the gpIII gene was inserted by site-directed mutagenesis. This mutated vector, MpComb3H-K2S, was transformed in XL-1 Blue. After induction with IPTG (isopropyl-beta-D-thiogalactopyranoside), rK2S was found both in the periplasm as an inactive form of approximately 32% and in the culture supernatant as an active form of approximately 68%. The secreted form of rK2S was partially purified by ammonium sulfate (55%) precipitation. The periplasmic form was isolated from whole cells by chloroform extraction. The fibrin binding site of kringle 2 was demonstrated in all expressed versions (phage-bound, periplasmic, and secreted forms) using the monoclonal anti-kringle 2 antibody (16/B). Only the secreted form of rK2S revealed a fibrinogen-dependent amidolytic activity with the specific activity of 236 IU/microg. No amidolytic activity of rK2S was observed in either the periplasmic or the phage-bound form. The secretion of rK2S as an active enzyme offers a novel approach for the production of the active-domain deletion mutant tPA, rK2S, without any requirements for bacterial compartment preparation and in vitro refolding processes. This finding is an important technological advance in the development of large-scale, bacterium-based tPA production systems.

Bacterial Outer Membrane Proteins↗
PubMed2001

Identification of the sigB operon in Staphylococcus epidermidis: construction and characterization of a sigB deletion mutant.

The role of the alternative sigma factor sigma(B) in Staphylococcus epidermidis was investigated by the construction, complementation, and characterization of a sigB deletion mutant. Electrophoretic analyses confirmed a profound influence of sigma(B) on the expression of exoproteins and cytoplasmic proteins. Detailed investigation revealed reduced lipase and enhanced protease activity in the sigma(B) mutant. Furthermore, no significant influence of sigma(B) on heterologous biofilm formation or on the activity of the global regulator agr was detected.

Bacterial Proteins↗
PubMed2001

Pheromone cross-inhibition between Staphylococcus aureus and Staphylococcus epidermidis.

Cross-inhibition by quorum-sensing pheromones between Staphylococcus aureus and Staphylococcus epidermidis was investigated using all known S. aureus agr pheromone subgroups. All S. aureus subgroups were sensitive towards the S. epidermidis pheromone, with the exception of the recently identified subgroup 4. The subgroup 4 pheromone was also the only S. aureus pheromone able to inhibit the S. epidermidis agr response. The close relation of subgroup 4 to subgroup 1 suggests that subgroup 4 might have evolved from subgroup 1 by mutation under the selective pressure of competition with S. epidermidis. The competition between S. aureus and S. epidermidis by means of quorum-sensing cross talk seems to be generally in favor of S. epidermidis, which might explain the predominance of S. epidermidis on the skin and in infections on indwelling medical devices.

Anti-Bacterial Agents↗
PubMed2001

Key role of teichoic acid net charge in Staphylococcus aureus colonization of artificial surfaces.

Staphylococcus aureus is responsible for a large percentage of infections associated with implanted biomedical devices. The molecular basis of primary adhesion to artificial surfaces is not yet understood. Here, we demonstrate that teichoic acids, highly charged cell wall polymers, play a key role in the first step of biofilm formation. An S. aureus mutant bearing a stronger negative surface charge due to the lack of D-alanine esters in its teichoic acids can no longer colonize polystyrene or glass. The mutation abrogates primary adhesion to plastic while production of the glucosamine-based polymer involved in later steps of biofilm formation is not affected. Our data suggest that repulsive electrostatic forces can lead to reduced staphylococcal biofilm formation, which could have considerable impact on the design of novel implanted materials.

Alanine↗
PubMed2001

Anaerobic conditions induce expression of polysaccharide intercellular adhesin in Staphylococcus aureus and Staphylococcus epidermidis.

Products of the intercellular adhesion (ica) operon in Staphylococcus aureus and Staphylococcus epidermidis synthesize a linear beta-1,6-linked glucosaminylglycan. This extracellular polysaccharide mediates bacterial cell-cell adhesion and is required for biofilm formation, which is thought to increase the virulence of both pathogens in association with prosthetic biomedical implants. The environmental signal(s) that triggers ica gene product and polysaccharide expression is unknown. Here we demonstrate that anaerobic in vitro growth conditions lead to increased polysaccharide expression in both S. aureus and S. epidermidis, although the regulation is less stringent in S. epidermidis. Anaerobiosis also dramatically stimulates ica-specific mRNA expression in ica- and polysaccharide-positive strains of both S. aureus and S. epidermidis. These data suggest a mechanism whereby ica gene expression and polysaccharide production may act as a virulence factor in an anaerobic environment in vivo.

Aerobiosis↗
PubMed2001

Genetic and epigenetic effects on sexual brain organization mediated by sex hormones.

Alterations of sex hormone levels during pre- or perinatal sexual brain organization - responsible for long-term changes of gonadotropin secretion, sexual orientation, and gender role behavior - can be caused by: 1. Genetic effects, i.e. mutations or polymorphisms of a) 21-hydroxylase genes on chromosome 6, b) 3beta-hydroxysteroid dehydrogenase genes in chromosome 1 or c) X-chromosomal genes, and 2. Epigenetic effects, such as a) stressful situations - especially in combination with mutations - and b) endocrine disrupters, e.g. the pesticide DDT and its metabolites, which display estrogenic, antiandrogenic, and inhibitory effects on the enzyme 3beta-hydroxysteroid dehydrogenase leading to increased levels of dehydroepiandrosterone and its sulfate as precursors of endogenous androgens and estrogens. In connection with the introduction and extensive use of the pesticide DDT, the following findings were obtained in subjects born before as compared to those born during this period: 1. The prevalence of patients with polycystic ovaries (PCO), idiopatic oligospermia (IO), and transsexualism (TS) increased significantly (about 3-4 fold). 2. Partial 21-hydroxylase deficiencies were observed in most patients with PCO and TS and some patients with IO born before this period. 3. In contrast, most patients with PCO and TS and several patients with IO born during the period of massive use of DDT displayed clearly increased plasma levels of dehydroepiandrosterone sulfate (DHEA-S) and DHEA-S/cortisol ratios suggesting partial 3beta-hydroxsteroid dehydrogenase (3beta-HSD) deficiencies. Interestingly enough, geneticists could not find any mutations of 3beta-HSD genes in such subjects. However, o,p'-DDT and/or its metabolite o,p'-DDD are strong inhibitors of 3beta-HSD, indicating their possible co-responsibility for such life-long ontogenetic alterations. Finally, some data suggest that endocrine disrupters may also be able to affect the development of sexual orientation.

Brain↗
PubMed2001

Female infertility--effect of perinatal xenoestrogen exposure on reproductive functions in animals and humans.

Environmental chemicals with inherent estrogenic activity are supposed to be responsible for the decrease of quantity and quality of human sperms during the past 40 years. The current hypothesis is that estrogenic agents acting during fetal life may lead to impaired development of the testes and of the male reproductive tract in the human as well as in several wildlife species. However, from clinical and experimental data it is known, that estrogens may also lead to impairment of female reproductive functions. Perinatal application of DDT, octylphenol and benzylbutylphthalate resulted in persistent estrus in rats, in- and subfertility, respectively, and impaired sexual behaviour. Epidemiological and experimental data speak in favour of environmental estrogens to be one cause for the development of polycystic ovaries, being the most important reason for female infertility in the human.

Adolescent↗
PubMed2000

Impact of the agr quorum-sensing system on adherence to polystyrene in Staphylococcus aureus.

Biofilm formation by Staphylococcus aureus is a serious problem in nosocomial infections. There are great differences in the capacity of S. aureus to express biofilms, but the reasons are unknown. In all, 105 S. aureus strains were tested for a correlation between the agr quorum-sensing system phenotype and the ability of S. aureus to adhere to polystyrene. Some 78% of agr-negative, but only 6% of agr-positive, strains formed a biofilm, demonstrating a profound impact of agr on biofilm formation. This result was confirmed with defined agr mutants and by inhibition of agr with quorum-sensing blockers. The observed effect was not due to differential expression of the autolysin Atl or of the exopolysaccharide polysaccharide intercellular adhesin but seemed to be caused, at least in part, by the surfactant properties of delta-toxin. The detected biofilm-enhancing effect of S. aureus quorum-sensing blockers call into question the proposed therapeutic use of such substances.

Bacterial Adhesion↗