Biomedical subjects

Christian Mayer

Publications and source records attributed to Christian Mayer.

15 recordsLinked to original sources

PubMed2006

The MPI Bioinformatics Toolkit for protein sequence analysis.

The MPI Bioinformatics Toolkit is an interactive web service which offers access to a great variety of public and in-house bioinformatics tools. They are grouped into different sections that support sequence searches, multiple alignment, secondary and tertiary structure prediction and classification. Several public tools are offered in customized versions that extend their functionality. For example, PSI-BLAST can be run against regularly updated standard databases, customized user databases or selectable sets of genomes. Another tool, Quick2D, integrates the results of various secondary structure, transmembrane and disorder prediction programs into one view. The Toolkit provides a friendly and intuitive user interface with an online help facility. As a key feature, various tools are interconnected so that the results of one tool can be forwarded to other tools. One could run PSI-BLAST, parse out a multiple alignment of selected hits and send the results to a cluster analysis tool. The Toolkit framework and the tools developed in-house will be packaged and freely available under the GNU Lesser General Public Licence (LGPL). The Toolkit can be accessed at http://toolkit.tuebingen.mpg.de.

Computational Biology↗

PubMed2006

Collapse of telechelic star polymers to watermelon structures.

Conformational properties of star-shaped polymer aggregates that carry attractive end groups, called telechelic star polymers, are investigated by simulation and analytical variational theory. We focus on the case of low telechelic star polymer functionalities, f < or = 5, a condition which allows aggregation of all attractive monomers on one site. We establish the functionality- and polymerization-number dependence of the transition temperature from the "star burst" to the "watermelon" macroparticle structure. Extensions to telechelic stars featuring partially collapsed configurations are also discussed.

Journal Article↗

PubMed2006

Lysosomal, cytoskeletal, and metabolic alterations in cardiomyopathy of cathepsin L knockout mice.

Although lysosomal proteases are expressed in the heart at considerable levels, their specific functions in this organ remain elusive. Mice deficient for the lysosomal cysteine protease cathepsin L (CTSL) develop a late onset dilated cardiomyopathy (DCM) that is characterized by cardiac chamber dilation, fibrosis, and impaired cardiac contraction at 12 month of age. Investigation of the pathogenic sequence of DCM in ctsl-/- mice revealed numerous dysmorphic lysosome-like structures in heart muscle as early as 3 days after birth, whereas skeletal muscle was not affected. Labeling of the acidic cell compartment of neonatal cardiomyocytes and detection of lysosomal markers after subcellular fractionation confirmed increased lysosome content in CTSL deficient myocardium; however, specific storage materials were not detected. The myocardium of ctsl+/+ and ctsl-/- mice revealed no differences in incidence of cell death, proliferation, and capillary density during DCM progression. However, an observed increase in mRNA expression of natriuretic peptides in young adult mice indicates the activation of the adaptive "fetal" gene program, while proteome analysis revealed decreased levels of the sarcomere-associated proteins alpha-tropomyosin, desmin, and calsarcin 1, as well as considerable changes of metabolic enzymes. Bioinformatic pathway analysis suggested a switch to anaerobic catabolism and impairment of mitochondrial respiration. This interpretation was supported by a 50% reduction in resting state oxygen consumption and impaired respiration capacity in ctsl-/- myocardial homogenates. In summary, the data indicate an essential role of CTSL in maintaining the structure of the endosomal/lysosomal compartment in cardiomyocytes. Lysosomal impairment in ctsl-/- hearts results in metabolic and sarcomeric alterations that promote DCM development.

Animals↗

PubMed2004

Equilibrium properties of highly asymmetric star-polymer mixtures.

We employ effective interaction potentials to study the equilibrium structure and phase behavior of highly asymmetric mixtures of star polymers. We consider in particular the influence of the addition of a component with a small number of arms and a small size on a concentrated solution of large stars with a high functionality. By employing liquid integral equation theories we examine the evolution of the correlation functions of the big stars upon addition of the small ones, finding a loss of structure that can be attributed to a weakening of the repulsions between the large stars due to the presence of the small ones. We analyze this phenomenon by means of a generalized depletion mechanism which is supported by computer simulations. By applying thermodynamic perturbation theory we draw the phase diagram of the asymmetric mixture, finding that the addition of small stars melts the crystal formed by the big ones. A systematic comparison between the two- and effective one-component descriptions of the mixture that corroborates the reliability of the generalized depletion picture is also carried out.

Journal Article↗

PubMed2004

Embedding and self-organization of nanoparticles in phospholipid multilayers.

Multilayers of various phospholipids on silicon substrates are used to induce spontaneous embedding of nanoparticles deposited from the gas phase. The resulting nanoparticle arrangement on the substrate surface is characterized using atomic force and scanning electron microscopy. In the intermediate phase and the liquid crystalline phase of the lipid, a monolayer is formed around individual nanoparticles which leads to an increase in interparticle distances. At the same time, the molecular mobility of the multilayers allows for self-assembly of the particles in regular two-dimensional arrangements.

Crystallization↗

PubMed2004

Molecular exchange through vesicle membranes: a pulsed field gradient nuclear magnetic resonance study.

The permeability of block copolymer vesicles is studied using pulsed field gradient nuclear magnetic resonance spectroscopy together with a numerical data analysis procedure. Polyethylene oxide molecules of various molecular masses are used to sample the permeability of the vesicle membrane by observing the trans-membrane exchange process under equilibrium conditions. For shorter polyethylene oxide chains, the analysis yields a nearly linear dependence of the logarithmic trans-membrane exchange rate on the hydrodynamic radius of the sample molecules.

Journal Article↗

PubMed2004

Structural characterization of Q10-loaded solid lipid nanoparticles by NMR spectroscopy.

PURPOSE: The structure of loaded solid lipid nanoparticles (SLN) has been studied to elucidate the incorporation of coenzyme Q10. METHODS: Solid-state nuclear magnetic resonance (NMR) has been applied as the principal analytical approach. In order to characterize the integration of the active ingredient coenzyme Q10 inside the solid lipid matrix, measurements of the spin-lattice relaxation time in the rotating frame have been performed. RESULTS: A pattern of spin diffusion between protons of the lipid and protons of the coenzyme Q10 has been observed, which indicates two different fractions of the active ingredient: whereas the majority (60%) of the coenzyme Q10 is found to be homogeneously mixed with the solid lipid, the residual amount of 40% clearly forms a separate, solid phase associated to the particles. CONCLUSIONS: A large portion of the active ingredient has been integrated homogeneously. Another, smaller fraction forms separate domains on the nanometer scale.

Drug Carriers↗

PubMed2004

Release of cell fragments by invading melanoma cells.

Tumor cell invasion requires coordinated cell adhesion to an extracellular matrix (ECM) substrate at the leading edge and concomitant detachment at the cell rear. Known detachment mechanisms include the slow sliding of focal contacts, the detachment of adhesion receptors by affinity and avidity regulation, as well as the shedding of adhesion receptors, most notably integrins. In highly invasive melanoma cells migrating within 3D collagen matrices, beta1 integrins and CD44 are released upon retraction of the trailing edge, together with ripping-off complete cell fragments to become deposited along the migration trail of remodeled matrix. Cell fragments reach a size up to 12 microm in diameter, contain cytoplasm and occasionally polymerized actin enclosed by intact cell membrane including surface beta1 integrins, but do not include nuclear material. The release of cell fragments was migration dependent, as impairment of motility by a blocking anti-beta1 integrin antibody also blocked cell particle release. Invasion-associated deposition of cell fragments combines the secretory-type release of vesicles with a physical mechanism of rear retraction and migration efficiency. The deposition of cell fragments may further represent a disregulated detachment strategy with implications for neoplastic cell behavior, such as the paracrine effects on neighbor cells or a negative impact on immune effector cells.

Cell Adhesion↗

PubMed2003

Structural behavior of nanometric carbohydrate films transduced by a resonant technique.

New optical nanoresonance effects enabled us to study the effect of ions on nanometric carbohydrate thin layers on chips. Immobilization was done via spin coating of the derivatized carbohydrate polymer at a metallized chip surface forming ultrathin films (about 50-300 nm thick) followed by photochemical cross-linking. Deposition of metal-nanoclusters, synthesized by chemical means and sputter coating on top of the polymer, induced an optical resonance effect, which transduced changes of polymer structure quantitatively into an optical signal that can be observed directly as resonance shift of a narrow optical peak. The response of the sensor chip even visible to the eye was quantified spectroscopically in the visible and ir range of the spectrum. The lifetime of thin film was good, and thus application as a sensor was limited only by the mechanical stability of the reactive matrix, but not by photobleaching or molecular leakage. Due to the inherent hydrophilic nature of the alginate polymer, the response time of this new sensor is governed by simple aqueous diffusion of the ionic calcium for up to 300 nm completed within less than one second. Monitoring of calcium fluctuations in a high background of magnesium and even serum was demonstrated with a dynamic range optimal for physiological measurements and a linear response up to 5 mM. Surface and alignment of polymer chain were influenced by the nanostructure of the supporting metal film-contrary to alginic acid, chitosan was deposited well aligned to the nanocrystals of the support.

Absorption↗

PubMed2003

13C-NMR study of the interaction of bacterial alginate with bivalent cations.

The effect of bivalent cations on solutions of extracellular polymeric substances (EPS) isolated from Pseudomonas aeruginosa was monitored by means of solid-state nuclear magnetic resonance. In particular, the binding of Ca2+ and Mg2+ to the alginate in aqueous solution was studied by determining the spin-lattice relaxation rates, line widths and line shapes of 13C nuclei under variation of the ion concentration. Both cations differ strongly in their affinity towards bacterial alginate. Spectral data indicate that the strong binding capacity of calcium is connected to the formation of a chelate complex, in which binding occurs particularly with the monomer units in alternating mannuronate-guluronate blocks. In contrast to this, binding of magnesium ions was found to be much weaker and non-specific.

Alginates↗

PubMed2003

Transient oscillations under strongly mismatched Hartmann-Hahn conditions.

Based on the standard 2D Polarization inversion experiment, a new pulse sequence (PI-TAPF) is proposed. It represents a combination of Polarization Inversion and TAPF (time averaged precession frequency) sequences. The depolarization period consists of phase-alternating intervals of different duration in the I channel. The pulse sequence yields transient oscillations under the strongly mismatched HH conditions where the required power for the dilute spins is reduced by a factor of 5. Experimental results recorded for a sample of ferrocene powder are well reproduced by numerical simulations.

Algorithms↗

PubMed2002

Prognostic value of 2D echocardiography in patients presenting with acute chest pain and non-diagnostic ECG for ST-elevation myocardial infarction.

The purpose of the present study was to test the hypothesis that early detection of regional wall motion abnormalities (WMA) by 2D echocardiography (ECHO) accurately predicts further cardiac events in patients presenting with acute chest pain. A prospective analysis was performed in subjects admitted with the first presentation of acute chest pain and a non-diagnostic ECG for acute ST-elevation myocardial infarction. Patients with known coronary artery disease were excluded. All subjects were contacted by phone for a 30days follow-up regarding cardiac events defined as PCI/CABG, AMI, and death. In 132 consecutive patients (89 male, 43 female) complete data sets consisting of case history (H; abnormal: typical angina), ECG (abnormal: ST-depression, T-inversion, atypical ST-elevation, LBBB), serum markers (TnI; abnormal: elevation of troponin I=0.5 ng/ml), ECHO (abnormal: WMA) and follow-up were available. In 45 patients, 60 cardiac events occurred (three deaths, 24 AMI, 33 PCI/CABG). Positive (PPV; %) and negative predictive values (NPV; %) of ECHO were superior to all other diagnostic tests (P<0.05 each) for adverse cardiac events, evolving AMI or death, and superior to history and ECG for later need of revascularisation (PCI/ACVB). Multivariate analysis revealed that WMA in ECHO predict cardiac events independently of age, gender, and the common combination of investigations (H/ECG/TnI). A significant independent impact of ECHO was also determined for the prediction of AMI/death or PCI/CABG. The study shows that early 2D echocardiography provides superior prognostic information concerning the risk of subsequent complications in patients with acute chest pain and a non-diagnostic ECG for ST-elevation-AMI.

Acute Disease↗

PubMed1999

Confocal imaging reveals activity-dependent intracellular Ca2+ transients in nociceptive human C fibres.

Unmyelinated nociceptive fibres are a key element in the human nociceptive system, however, it is very difficult to investigate such fibres in vivo in more detail. An alternate approach are studies on isolated human nerves. Here we describe that confocal Ca2+ imaging reveals new information about the physiology of human nociceptive C fibres. Confocal images at two emission wavelengths were collected from regions with unmyelinated nerve fibres within segments of biopsied human sural nerves stained with the Ca2+-sensitive fluorescent dyes Calcium Green-1 and Fura Red. Short trains of supramaximal electrical stimuli applied to one end of the nerve as well as bath application of capsaicin resulted in an increase in the free intracellular Ca2+ concentration. Intracellular Ca2+ transients were seen at action potential frequencies above 1 Hz. They were absent in Ca2+-free bathing solution and reduced during bath application of cadmium. This indicates an extracellular source of the activity-dependent rise in [Ca2+]i. Furthermore, Ca2+ transients were also observed during elevation of the extracellular K+ concentration or during short trains of calcium action potentials. Such 'Ca2+ spikes' were elicited by a combination of tetrodotoxin and potassium channel blockers. These data suggest the presence of voltage-dependent Ca2+ channels in the membrane of nociceptive human nerve fibres.

Action Potentials↗

PubMedDate not supplied

Phage display antibody-based proteomic device using resonance-enhanced detection.

The combination of phage display antibody arrays with a novel nanotransducer technique based on resonant nanoparticles in a nanosandwiched film enables the sensitive parallel screening of proteins. Using the resonance of nanoparticles with their induced mirror dipoles in a thin-film structure, limitations of fluorophores, such as unspecific background and nonvisibility to the eye, can be overcome, thereby leading to an optical signal significantly more sensitive than that of standard colloid techniques. The signal can be both directly observed as a color change of a microdot at the sensor surface and tuned throughout the visible range of the spectrum. Here we report the application of an optical chip using scFv-antibody-antigen interactions. Artificial scFv-antibodies against a variety of proteins, including yeast enzymes and bovine serum albumin (as a standard), were constructed via Phage Display. These scFv-antibodies were then coated onto metal nanoclusters and bound to their antigens that were arrayed as nanodroplets at the resonance layer of the chip. ScFv-Antibody-antigen interaction resulted in a visible array of microdots. Using resonance-enhanced absorption, the absorption signal of the spots was amplified by one to two orders of magnitude (compared to colloid-based techniques). For quantitative analysis, either an 8-micron scanner or a CCD camera (resolution 4 microns) was employed to gain direct-reflection spectra rather than unspecific scatter data (prone to dust and unspecific interaction). Our results demonstrate that this device enables high-throughput proteomics to overcome some limitations of fluorescence, enzyme labels, and colloid techniques.

Antibodies↗

PubMedDate not supplied

Tuning the setup of sputter-coated multilayers in nanocluster-based signal-enhancing biochips for optimal performance in protein and DNA assays.

In biochip development two issues are critical: stable and specific immobilization of the ligand and achievement of high signal-to-background ratio. In this work we have addressed these issues for the development of biochips, produced by sputtering multilayers of thin metal films, metal oxides, and metal nitrides (tens to hundreds of nanometers thick) onto glass wafers. Optimized surfaces have shown good results in genomic and proteomic experiments with biochips based on surface-enhanced fluorescence and absorption techniques.

Adsorption↗