Biomedical subjects

Christoph Meier

Publications and source records attributed to Christoph Meier.

15 recordsLinked to original sources

PubMed2006

Erythropoietin (EPO): EPO-receptor signaling improves early endochondral ossification and mechanical strength in fracture healing.

Beyond its role in the regulation of red blood cell proliferation, the glycoprotein erythropoietin (EPO) has been shown to promote cell regeneration and angiogenesis in a variety of different tissues. In addition, EPO has been indicated to share significant functional and structural homologies with the vascular endothelial growth factor (VEGF), a cytokine essential in the process of fracture healing. However, there is complete lack of information on the action of EPO in bone repair and fracture healing. Therefore, we investigated the effect of EPO treatment on bone healing in a murine closed femur fracture model using radiological, histomorphometric, immunohistochemical, biomechanical and protein biochemical analysis. Thirty-six SKH1-hr mice were treated with daily i.p. injections of 5000 U/kg EPO from day 1 before fracture until day 4 after fracture. Controls received equivalent amounts of the vehicle. After 2 weeks of fracture healing, we could demonstrate expression of the EPO-receptor (EPOR) in terminally differentiating chondrocytes within the callus. At this time point EPO-treated animals showed a higher torsional stiffness (biomechanical analysis: 39.6+/-19.4% of the contralateral unfractured femur) and an increased callus density (X-ray analysis (callus density/spongiosa density): 110.5+/-7.1%) when compared to vehicle-treated controls (14.3+/-8.2% and 105.9+/-6.6%; p<0.05). Accordingly, the histomorphometric examination revealed an increased fraction of mineralized bone and osteoid (33.0+/-3.0% versus 28.5+/-3.6%; p<0.05). Of interest, this early effect of the initial 6-day EPO treatment had vanished at 5 weeks after fracture. We conclude that EPO-EPOR signaling is involved in the process of early endochondral ossification, enhancing the transition of soft callus to hard callus.

Animals↗

PubMed2006

Measurement of compartment pressure of the rectus sheath during intra-abdominal hypertension in rats.

OBJECTIVE: To investigate whether the compartment pressure of the rectus sheath (CPRS) reflects the intra-abdominal pressure (IAP) under various conditions of intra-abdominal hypertension (IAH). DESIGN AND SETTING: Prospective experimental study with in vivo pressure measurements at the Institute for Clinical and Experimental Surgery, University of Saarland. ANIMALS: Sprague-Dawley rats. INTERVENTIONS: Stepwise increase and decrease in IAP with continuous measurement of the correspondent CPRS. MEASUREMENTS AND RESULTS: Physiological IAP (2 mmHg) and CPRS (6 mmHg) showed a statistically significant difference. Stepwise elevation in IAP was associated with a simultaneous increase in CPRS. Accordingly, stepwise decompression of IAP resulted in a stepwise decrease in CPRS. Under both conditions Bland-Altman analysis comparing IAP to correspondent CPRS showed a very good agreement for IAP at or above 12 mmHg. In addition, closure of the overlaying subcutaneous tissue and skin did not affect CPRS or its correlation with IAP. CONCLUSIONS: CPRS accurately reflects IAP for IAP of 12 mmHg or higher. Thus CPRS measurements may represent a novel approach for diagnosis and monitoring of IAH.

Abdomen↗

PubMed2006

Investigation of the dynamics of two coupled oscillators with mixed quantum-classical methods.

The dynamics of two coupled oscillators can become quite complex if anharmonic potential energy functions are employed. This type of system therefore represents a good model for an investigation of the performance of mixed quantum-classical methods. In this work, the motion of two coupled particles with a mass ratio of one to ten is studied with three different mixed quantum-classical methods in the presence of anharmonic potential terms for a comparison with exact quantum mechanical calculations. The mixed quantum-classical approaches include the multitrajectory Ehrenfest, the mixed quantum-classical Bohmian (MQCB), and the so-called coupled Schrödinger equations (CSE) formalisms. The analysis shows that while the description of a weakly anharmonic system by the Ehrenfest and MQCB schemes is accurate if proper sampling techniques are applied, both approximations break down rapidly if the anharmonic terms are increased. The performance of the simple CSE prescription, which corresponds to a reduction of the full two-dimensional wave function to two one-dimensional wave functions representing two quantum oscillators coupled via the potential energy in a classical fashion, decreases if the width of the initial wave packet is enlarged. The dependence of the CSE method on the diffuseness of the initial wave packet is therefore opposite to that of the MQCB method, which is more accurate for wide wave packets. Overall, the multitrajectory Ehrenfest ansatz is found to be most successful in reproducing the exact quantum results.

Algorithms↗

PubMed2006

Visualizing picometric quantum ripples of ultrafast wave-packet interference.

Interference fringes in vibrating molecules are a signature of quantum mechanics, but are often so short-lived and closely spaced that they elude visualization. We have experimentally visualized dynamical quantum interferences, which appear and disappear in less than 100 femtoseconds in the iodine molecule synchronously with the periodic crossing of two counterpropagating nuclear wave packets. The obtained images have picometer and femtosecond spatiotemporal resolution, representing a detailed picture of the quantum interference.

Journal Article↗

PubMed2006

The crystal structure of ORF-9b, a lipid binding protein from the SARS coronavirus.

To achieve the greatest output from their limited genomes, viruses frequently make use of alternative open reading frames, in which translation is initiated from a start codon within an existing gene and, being out of frame, gives rise to a distinct protein product. These alternative protein products are, as yet, poorly characterized structurally. Here we report the crystal structure of ORF-9b, an alternative open reading frame within the nucleocapsid (N) gene from the SARS coronavirus. The protein has a novel fold, a dimeric tent-like beta structure with an amphipathic surface, and a central hydrophobic cavity that binds lipid molecules. This cavity is likely to be involved in membrane attachment and, in mammalian cells, ORF-9b associates with intracellular vesicles, consistent with a role in the assembly of the virion. Analysis of ORF-9b and other overlapping genes suggests that they provide snapshots of the early evolution of novel protein folds.

Amino Acid Sequence↗

PubMed2006

Lysine methylation as a routine rescue strategy for protein crystallization.

Crystallization remains a critical step in X-ray structure determination. Because it is not generally possible to rationally predict crystallization conditions, commercial screens have been developed which sample a wide range of crystallization space. While this approach has proved successful in many cases, a significant number of proteins fail to crystallize despite being soluble and monodispersed. It is established that chemical modification can facilitate the crystallization of otherwise intractable proteins. Here we describe a method for the reductive methylation of lysine residues which is simple, inexpensive, and efficient, and report on its application to ten proteins. We describe the effect of methylation on the physico-chemical properties of these proteins, and show that it led to diffraction-quality crystals from four proteins and structures for three that had hitherto proved refractory to crystallization. The method is suited to both low- and high-throughput laboratories.

Bacillus anthracis↗

PubMed2006

Bacterial community structure of a pesticide-contaminated site and assessment of changes induced in community structure during bioremediation.

The introduction of culture-independent molecular screening techniques, especially based on 16S rRNA gene sequences, has allowed microbiologists to examine a facet of microbial diversity not necessarily reflected by the results of culturing studies. The bacterial community structure was studied for a pesticide-contaminated site that was subsequently remediated using an efficient degradative strain Arthrobacter protophormiae RKJ100. The efficiency of the bioremediation process was assessed by monitoring the depletion of the pollutant, and the effect of addition of an exogenous strain on the existing soil community structure was determined using molecular techniques. The 16S rRNA gene pool amplified from the soil metagenome was cloned and restriction fragment length polymorphism studies revealed 46 different phylotypes on the basis of similar banding patterns. Sequencing of representative clones of each phylotype showed that the community structure of the pesticide-contaminated soil was mainly constituted by Proteobacteria and Actinomycetes. Terminal restriction fragment length polymorphism analysis showed only nonsignificant changes in community structure during the process of bioremediation. Immobilized cells of strain RKJ100 enhanced pollutant degradation but seemed to have no detectable effects on the existing bacterial community structure.

Arthrobacter↗

PubMed2006

Adipose tissue has anti-inflammatory properties: focus on IL-1 receptor antagonist (IL-1Ra).

The formation of adipose tissue could result from abnormal metabolic processes and, at the local level, from chronic inflammatory processes such as those occurring in the synovial cavity in rheumatoid arthritis or osteoarthritis, or the peritoneal cavity in various inflammatory processes of the digestive system. Adipocytes are said to produce many hormones and proinflammatory mediators. So far, however, little attention has been paid to cytokine inhibitory molecules. Based on our observation of high levels of serum interleukin receptor antagonist (IL-1Ra) in obese patients contrasting with decreased levels after gastric bypass surgery, we found white adipose tissue (WAT) in the human system to be the main source of IL-1Ra. IL-10 was also present in WAT. Furthermore, we found that interferon-beta (IFN)-beta was the principal cytokine inducing IL-1Ra in various WAT, such as that present in the synovium. We suggest that in addition to other functions adipose tissue may give rise to a host-defense mechanism against local inflammation and that fibrotic tissue in the vicinity may further induce IL-1Ra in adipocytes via the production of IFN-beta.

Adipose Tissue↗

PubMed2006

Elastic stable intramedullary nailing for midclavicular fractures in athletes: indications, technical pitfalls and early results.

This prospective consecutive case series was done to evaluate indications, technical pitfalls and functional outcome of elastic stable intramedullary nailing of displaced midclavicular fractures in 14 athletes. Constant score and radiographs were evaluated after 1 and 6 weeks, 3 months and 6 months in 13 patients. Mean age was 28 years. The average follow-up was 17 months. Mean operation time was 62 minutes. Open reduction through an additional small incision was necessary for 7 fractures. Mean hospital stay was 1.2 days. Secondary fracture displacement was observed in 1 patient. The Constant score averaged 81 after 1 week, 96 after 6 weeks and 98 after 6 months. Compared to the contralateral side, average shortening of the clavicle was 1.7 mm. Overall, elastic stable intramedullary nailing provided good restoration of the length of the clavicle and allowed immediate active mobilisation with early return to normal activity. Functional results were excellent.

Adolescent↗

PubMed2005

Combining fixed- and moving-grid methods to study direct dissociation processes involving nonadiabatic transitions.

We present a novel quantum-dynamics approach suitable for computing direct dissociation processes, including electronic transitions. This approach combines quantum trajectories in the Lagrangian reference frame with standard fixed-grid wave packets in order to overcome the limitations and difficulties of both techniques. As a model application, we consider the ultrafast photodissociation of H2 excited by a femtosecond extreme UV laser pulse.

Journal Article↗

PubMed2005

Local control of molecular fragmentation: the role of orientation.

Local control theory, where the instantaneous response of a system to an external field determines the control field, is employed for the purpose of inducing molecular fragmentation processes via infrared excitation. In particular, the effects of the orientational motion are investigated and compared with the idealized case of a frozen rotation. It is shown that the rotational degree of freedom is crucial for the applicability of the employed local control algorithm. The addition of an additional static electric field which induces a molecular preorientation offers an efficient way for the local control. In particular, with increasing static field strength, the fragmentation yield approaches unity so that the idealized rotationless case is recovered. Numerical results are presented for the NaI molecule.

Journal Article↗

PubMed2005

Weak hydrogen bonds as a structural motif for two-dimensional assemblies of oligopyridines on highly oriented pyrolytic graphite: an STM investigation.

We present the STM investigation of four different oligopyridines at the liquid/highly oriented pyrolytic graphite interface. The heteroaromatic compounds are constitutional isomers showing the same overall shape regardless of their actual conformation. On the basis of weak intermolecular C-H...N hydrogen-bonding interactions, different nanopatterns are formed following a simple general concept for the two dimensional self-assembly. The molecules arrange either in linear or in cyclic structures. Though the oligopyridines are achiral, the formation of prochiral trimeric superstructures leads to chiral phases due to the immobilization on the surface. Some of the molecules show polymorphic structures depending on the solvent. The large variety of the presented structures formed by self-assembly of the different oligopyridines which retain the same functional heteroaromatic backbone shall open the possibility of exploiting these patterns as templates for the nanostructuring of surfaces with guests such as small molecules or metal ions for intriguing applications in, for example, catalysis.

Journal Article↗

PubMed2005

Overcoming the false-minima problem in direct methods: structure determination of the packaging enzyme P4 from bacteriophage phi13.

The problems encountered during the phasing and structure determination of the packaging enzyme P4 from bacteriophage phi13 using the anomalous signal from selenium in a single-wavelength anomalous dispersion experiment (SAD) are described. The oligomeric state of P4 in the virus is a hexamer (with sixfold rotational symmetry) and it crystallizes in space group C2, with four hexamers in the crystallographic asymmetric unit. Current state-of-the-art ab initio phasing software yielded solutions consisting of 96 atoms arranged as sixfold symmetric clusters of Se atoms. However, although these solutions showed high correlation coefficients indicative that the substructure had been solved, the resulting phases produced uninterpretable electron-density maps. Only after further analysis were correct solutions found (also of 96 atoms), leading to the eventual identification of the positions of 120 Se atoms. Here, it is demonstrated how the difficulties in finding a correct phase solution arise from an intricate false-minima problem.

Crystallization↗

PubMed2005

Laser control of vibrational excitation in carboxyhemoglobin: a quantum wave packet study.

A coherent control algorithm is applied to obtain complex-shaped infrared laser pulses for the selective vibrational excitation of carbon monoxide at the active site of carbonmonoxyhemoglobin, modeled by the six-coordinated iron-porphyrin-imidazole-CO complex. The influence of the distal histidine is taken into account by an additional imidazole molecule. Density-functional theory is employed to calculate a multidimensional ground-state potential energy surface, and the vibrational dynamics as well as the laser interaction is described by quantum wave-packet calculations. At each instant in time, the optimal electric field is calculated and used for the subsequent quantum dynamics. The results presented show that the control scheme is applicable to complex systems and that it yields laser pulses with complex time-frequency structures, which, nevertheless, have a clear physical interpretation.

Algorithms↗

PubMed2003

A molecular dynamics investigation of mono and dimeric states of the outer membrane enzyme OMPLA.

OMPLA is a phospholipase found in the outer membranes of many Gram-negative bacteria. Enzyme activation requires calcium-induced dimerisation plus bilayer perturbation. As the conformation of OMPLA in the different crystal forms (monomer versus dimer; with/without bound Ca(2+)) is remarkably similar we have used multi-nanosecond molecular dynamics (MD) simulations to probe possible differences in conformational dynamics that may be related to enzyme activation. Simulations of calcium-free monomeric OMPLA, of the Ca(2+)-bound dimer, and of the Ca(2+)-bound dimer with a substrate analogue covalently linked to the active site serine have been performed, all with the protein embedded in a phospholipid (POPC) bilayer. All simulations were stable, but differences in the dynamic behaviour of the protein between the various states were observed. In particular, the stability of the active site and the hydrophobic substrate-binding cleft varied. Dimeric OMPLA is less flexible than monomeric OMPLA, especially around the active site. In the absence of bound substrate analogue, the hydrophobic substrate-binding cleft of dimeric OMPLA collapses. A model is proposed whereby the increased stability of the active site in dimeric OMPLA is a consequence of the local ordering of water around the nearby calcium ion. The observed collapse of the substrate-binding cleft may explain the experimentally observed occurrence of multiple dimer conformations of OMPLA, one of which is fully active while the other shows significantly reduced activity.

Bacterial Outer Membrane Proteins↗