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Biomedical subjects

R Kern

Publications and source records attributed to R Kern.

At least 19 recordsLinked to original sources

Visually guided orientation in flies: case studies in computational neuroethology.

To understand the functioning of nervous systems and, in particular, how they control behaviour we must bridge many levels of complexity from molecules, cells and synapses to perception behaviour. Although experimental analysis is a precondition for understanding by nervous systems, it is in no way sufficient. The understanding is aided at all levels of complexity by modelling. Modelling proved to be an inevitable tool to test the experimentally established hypotheses. In this review it will by exemplified by three case studies that the appropriate level of modelling needs to be adjusted to the particular computational problems that are to be solved. (1) Specific features of the highly virtuosic pursuit behaviour of male flies can be understood on the basis of a phenomenological model that relates the visual input to the motor output. (2) The processing of retinal image motion as is experienced by freely moving animals can be understood on the basis of a model consisting of algorithmic components and components which represent a simple equivalent circuit of nerve cells. (3) Behaviourally relevant features of the reliability of encoding of visual motion information can be understood by modelling the transformation of postsynaptic potentials into sequences of spike trains.

Animals↗

FliMax, a novel stimulus device for panoramic and highspeed presentation of behaviourally generated optic flow.

A high-speed panoramic visual stimulation device is introduced which is suitable to analyse visual interneurons during stimulation with rapid image displacements as experienced by fast moving animals. The responses of an identified motion sensitive neuron in the visual system of the blowfly to behaviourally generated image sequences are very complex and hard to predict from the established input circuitry of the neuron. This finding suggests that the computational significance of visual interneurons can only be assessed if they are characterised not only by conventional stimuli as are often used for systems analysis, but also by behaviourally relevant input.

Animals↗

Chaperone-like properties of lysophospholipids.

Lysophospholipids are metabolic intermediates in phospholipid turnover, detergent molecules with membrane-modulating effects, and multifunctional cellular growth factors in eukaryotic cells. In bacterial cells, lysophospholipids are mostly found in the form of lysophosphatidylethanolamine. We show that a heat shock from 30 to 42 degrees C increases four-fold the Escherichia coli pool of lysophosphoethanolamine and that lysophospholipids display chaperone-like properties. Lysophosphatidylethanolamine, like molecular chaperones such as DnaK, promotes the functional folding of citrate synthase and alpha-glucosidase after urea denaturation. Like chaperones, lysophophatidylethanolamine, lysophosphatidylcholine, lysophosphatidylinositol and lysophosphatidic acid prevent the aggregation of citrate synthase at 42 degrees C. The renaturation and solubilisation of proteins by lysophospholipids occur at micromolar concentrations of these compounds, close to their critical micellar concentration. Furthermore, lysophosphatidylethanolamine is much more efficient than other detergents tested for the renaturation and solubilisation of citrate synthase. In contrast with lysophospholipids, phosphatidylethanolamine and phosphatidylcholine are not able to promote citrate synthase folding nor to prevent its aggregation at 42 degrees C. The chaperone-like properties of lysophospholipids suggest that, in addition to their known functions, they might affect the structure and function of hydrophilic proteins.

Bacterial Proteins↗

Neural processing of naturalistic optic flow.

Stimuli traditionally used for analyzing visual information processing are much simpler than what an animal sees in normal life. When characterized with traditional stimuli, neuronal responses were found to depend on various parameters such as contrast, texture, or velocity of motion, and thus were highly ambiguous. In behavioral situations, all of these parameters change simultaneously and differently in different parts of the visual field. Thus it is hardly possible to predict from traditional analyses what information is encoded by neurons in behavioral situations. Therefore, we characterized an identified neuron in the optomotor system of the blowfly with image sequences as they were seen by animals walking in a structured environment. We conclude that during walking, the response of the neuron reflects the animal's turning direction nearly independently of the texture and spatial layout of the environment. Our findings stress the significance of analyzing the performance of neuronal circuits under their natural operating conditions.

Animals↗

Outdoor performance of a motion-sensitive neuron in the blowfly.

We studied an identified motion-sensitive neuron of the blowfly under outdoor conditions. The neuron was stimulated by oscillating the fly in a rural environment. We analysed whether the motion-induced neuronal activity is affected by brightness changes ranging between bright sunlight and dusk. In addition, the relationship between spike rate and ambient temperature was determined. The main results are: (1) The mean spike rate elicited by visual motion is largely independent of brightness changes over several orders of magnitude as they occur as a consequence of positional changes of the sun. Even during dusk the neuron responds strongly and directionally selective to motion. (2) The neuronal spike rate is not significantly affected by short-term brightness changes caused by clouds temporarily occluding the sun. (3) In contrast, the neuronal activity is much affected by changes in ambient temperature.

Adaptation, Ocular↗

Molecular microbial diversity of a spacecraft assembly facility.

In ongoing investigations to map and archive the microbial footprints in various components of the spacecraft and its accessories, we have examined the microbial populations of the Jet Propulsion Laboratory's Spacecraft Assembly Facility (JPL-SAF). Witness plates made up of spacecraft materials, some painted with spacecraft qualified paints, were exposed for approximately 7 to 9 months at JPL-SAF and examined the particulate materials collected for the incidence of total cultivable aerobic heterotrophs and heat-tolerant (80 degrees C for 15-min.) spore-formers. The results showed that the witness plates coated with spacecraft qualified paints attracted more dust particles than the non-coated stainless steel witness plates. Among the four paints tested, witness plates coated with NS43G accumulated the highest number of particles, and hence attracted more cultivable microbes. The conventional microbiological examination revealed that the JPL-SAF harbors mainly Gram-positive microbes and mostly spore-forming Bacillus species. Most of the isolated microbes were heat resistant to 80 degrees C and proliferate at 60 degrees C. The phylogenetic relationships among 23 cultivable heat-tolerant microbes were examined using a battery of morphological, physiological, molecular and chemotaxonomic characterizations. By 16S rDNA sequence analysis, the isolates fell into seven clades: Bacillus licheniformis, B. pumilus, B. cereus, B. circulans, Staphylococcus capitis, Planococcus sp. and Micrococcus lylae. In contrast to the cultivable approach, direct DNA isolation, cloning and 16S rDNA sequencing analysis revealed equal representation of both Gram-positive and Gram-negative microorganisms.

Bacillus↗

Acute stroke patterns in patients with internal carotid artery disease: a diffusion-weighted magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Diffusion-weighted (DW) MRI is a sensitive method that facilitates early stroke pattern identification. There are limited data about the influence of stenosis grade on the development of particular stroke patterns in internal carotid artery (ICA) disease. We therefore investigated the lesion patterns on DW MRI in acute stroke patients with ICA disease. METHODS: DW MRI was analyzed in 102 consecutive acute stroke patients with different degrees of ipsilateral ICA disease. Patients were assigned to 1 of 5 observed lesion patterns: (1) territorial ischemia, (2) subcortical ischemia without or (3) with embolus fragmentation, (4) disseminated lesions in distal cortical regions, and (5) multiple lesions in hemodynamic risk zones. In addition, perfusion-weighted (PW) MRI and MR angiography information was included in the assessment. RESULTS: All patterns were observed in the different stages of ICA disease. Half of the patients with high-grade or subtotal stenosis had lesions in hemodynamic risk zones. Territorial stroke occurred in 47.6% of patients with ICA occlusion. Statistical analysis showed a significant relationship between the degree of stenosis and the observed stroke pattern (P=0.001). In 77.8% of patients exhibiting high-grade ICA stenosis, subtotal stenosis, or occlusion, the perfusion lesion was larger than the diffusion lesion (PW/DW mismatch). CONCLUSIONS: Although in the individual patient any of the infarct patterns may occur, in statistical terms the incidence of a particular stroke pattern is clearly dependent on the degree of stenosis.

Aged↗

Neuronal processing of behaviourally generated optic flow: experiments and model simulations.

The stimuli traditionally used for analysing visual information processing are much simpler than what an animal sees when moving in its natural environment. Therefore, we analysed in a previous study the performance of an identified neuron in the optomotor system of the fly by using as visual stimuli image sequences that were experienced by the animal while walking in a structured environment. These electrophysiological experiments revealed that the fly visual system computes from behaviourally generated optic flow a rather unambiguous representation of the animal's self-motion. In contrast to conclusions based on simple stimuli, the directions of turns are represented by an interneuron, the HSE cell, quite independent of the spatial layout of the environment and its textural properties when the cell is stimulated with behaviourally generated optic flow. This conclusion is substantiated here by further experimental evidence. Moreover, it is shown that the largely unambiguous responses of the HSE cell to behaviourally generated optic flow can be replicated to a large extent by a network model of the fly's visual motion pathway. These results stress the significance of naturalistic stimuli for analysing what is encoded by neuronal circuits under natural operating conditions.

Algorithms↗

Assessment of acute cyto- and genotoxicity of corrosion eluates obtained from orthodontic materials using monolayer cultures of immortalized human gingival keratinocytes.

Whilst a patient is undergoing orthodontic treatment, dental appliances based on non-precious metals or titanium remain in the oral cavity for up to several years. Throughout this period the appliance is in either direct or indirect contact with the oral mucosa. To investigate the possibility of cell damage occurring as a result of appliance corrosion, monolayer cultures of immortalized human gingival keratinocytes were assessed for acute cyto- and genotoxicity using the hexosaminidase assay and the Comet assay respectively. The materials tested included 1. a nickel-free wire, 2. a UK-1 bond, 3. nickel-free as well as nickel-containing brackets with and without color signature and 4. a titanium expansion screw. Each of the test materials was corroded in a solution consisting of equal amounts of lactic acid and sodium chloride (0.1 M) for 1, 3, 7 and 14 days. The cell cultures were then exposed to eluates exhibiting the highest ion concentrations. None of the eluates was found to exhibit acute cytotoxicity, regardless of the type of test system used. Qualitative assessment using neutral red dye for live cells and either trypan blue or propidium iodide to disclose dead cells failed to reveal any significant increase in cell damage when exposed cells were compared to control cultures. Unrestricted cell vitality was confirmed by quantifying viable cells through measurement of hexosaminidase enzyme activity. Furthermore, assessment of genotoxicity revealed no apparent DNA damage to immortalized gingival keratinocytes following exposure to the test eluates. Because the materials tested in this study were corroded using the exacting methods normally applied to precious metals or gold-containing alloys, the lack of either acute cyto- or genotoxic effects following exposure to the test eluates indicates that the materials tested exert no adverse effects on cells similar to those of the target tissue exposed to the materials in situ.

Cell Culture Techniques↗

Optomotor course control in flies with largely asymmetric visual input.

We have studied freely flying and walking flies as well as flies flying in a flight simulator in order to discover how functionally blinding one of the eyes affects the fly's ability to move straight. It is hard to tell just by observing the animals' movements whether they have been deprived of vision in one eye. Statistical analysis is need to show that there are differences in the locomotory paths of monocular and binocular flies: monocular flies tend to turn slightly towards the side of the seeing eye. It is possible that the superimposed translational and rotational optic flow fields, generated on the trajectory of monocular flies, sum to zero net flow. This overall flow over the retina of the open eye might lead to a state of optomotor equilibrium.

Animals↗

Neuronal representation of optic flow experienced by unilaterally blinded flies on their mean walking trajectories.

Asymmetries in the optic flow on both eyes may indicate an unintended turn of an animal and evoke compensatory optomotor responses. On a straight path in an evenly structured environment, the optic flow on both eyes is balanced corresponding to a state of optomotor equilibrium. When one eye is occluded an optomotor equilibrium is expected to be reached on a curved path provided that the translatory optic flow component is cancelled by a superimposed rotation. This hypothesis is tested by analysing how the HSE cell, a constituent element of the fly's optomotor system, represents optic flow in behavioural situations. The optic flow as seen on the average trajectory of freely walking monocular flies is reconstructed. This optic flow is used as stimulus of the HSE cell in electrophysiological experiments and as input of a model of the fly's optomotor system. The responses of the HSE cell and of the model fluctuate around the resting potential. On average, they are much smaller than the responses evoked by optic flow experienced on a straight path. These results corroborate the hypothesis that the mean trajectory of monocular flies corresponds to a path of optomotor equilibrium.

Animals↗

Competition between the replication initiator DnaA and the sequestration factor SeqA for binding to the hemimethylated chromosomal origin of E. coli in vitro.

BACKGROUND: Following replication initiation, the replication origin (oriC) in Escherichia coli enters a hemimethylated state at Dam methylation sites which are recognized by the SeqA protein. SeqA binds preferentially to hemimethylated GATC sequences of DNA in vitro. SeqA is essential for the synchronous initiation of chromosome replication from oriC copies in vivo. RESULTS: We show that: (i) purified SeqA binds AT-rich and 13-mers regions and two DnaA boxes, R1 and M, of hemimethylated oriC. (ii) SeqA inhibits the in vitro replication of a hemimethylated oriC plasmid more efficiently than the fully methylated, (iii) SeqA inhibits competitive binding of DnaA protein to the regions of the hemimethylated oriC plasmid, explaining the mechanism of its inhibitory effect. The inhibition of DnaA binding by SeqA also occurs efficiently on a small hemimethylated oriC fragment containing both R1 and M DnaA boxes, but not the 13-mer region. CONCLUSIONS: SeqA binds strongly the long region from the AT-rich region to the M DnaA box of the hemimethylated oriC DNA and releases DnaA molecules from the long region.

AT Rich Sequence↗

Arterial gas embolism after decompression: correlation with right-to-left shunting.

Paradoxical gas embolism is a possible cause of neurologic sequelae after decompression in divers. The authors detected arterial bubbles after decompression from chamber dives in two of six divers using transcranial Doppler sonography (TCD). Arterial bubbles correlated with the size of right-to-left shunting as diagnosed by contrast TCD. The pathway of spontaneous paradoxical embolism was tracked for the first time, supporting the concept of paradoxical gas embolism as a cause of early neurologic sequelae after decompression in at-risk divers.

Adult↗

Application of pharmacokinetics to electron-beam tomography of the abdomen.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the pharmacokinetics of abdominal time-attenuation curves obtained at electron-beam tomography. MATERIALS AND METHODS: Computed tomographic enhancement data of the aorta, portal vein, vena cava, liver, spleen, and pancreas were obtained in 25 patients after injection of 50 mL of contrast medium. These data were used to calculate pharmacokinetic parameters such as half-lives, mean residence times, and areas under the curve with a computer program. RESULTS: Maximal enhancement was observed in the aorta 24 seconds +/- 5 (mean +/- standard deviation) after starting the injection of contrast medium (178 HU +/- 56), in the portal vein after 42 seconds +/- 14 (60 HU +/- 17), in the vena cava after 35 seconds +/- 7 (66 HU +/- 23), in the liver after 58 seconds +/- 15 (24 HU +/- 6), in the spleen after 35 seconds +/- 12 (42 HU +/- 16), and in the pancreas after 39 seconds +/- 15 (42 HU +/- 10). Half-lives of the last phase observed were 108 seconds +/- 123 in the aorta, 33 seconds +/- 30 in the portal vein, 49 seconds +/- 40 in the vena cava, 50 seconds +/- 54 in the liver, 62 seconds +/- 33 in the spleen, and 22 seconds +/- 27 in the pancreas. The computer program allowed for excellent fitting curves to the measured attenuation values and for subsequent calculation of pharmacokinetic parameters. New dosage regimens also could be simulated successfully. CONCLUSION: The pharmacokinetic parameters evaluated might be useful in the optimization of dosing and scanning parameters of the abdomen for ultrafast and helical CT.

Aorta, Abdominal↗

Hemi-methylated oriC DNA binding activity found in non-specific acid phosphatase.

The lacZ-hobH fusion clone, containing an Escherichia coli DNA segment located at 92 min on the chromosomal map, was screened as a producer of E. coli oriC hemi-methylated binding activity. We have purified the protein encoded by this locus to near homogeneity. The protein corresponds to the monomeric form of a non-specific acid phosphatase (NAP) whose gene has been designated aphA. oriC DNA footprinting experiments showed protection of hemi-methylated probe by partially purified NAP, but not by purified preparations. Yet, gel retardation experiments with an oriC oligonucleotide demonstrated DNA binding activity of purified NAP in the presence of Mg2+. This experiment also showed an increased affinity of the protein for the hemi-methylated probe compared with the fully or unmethylated form. Indirect immunofluorescene microscopy revealed the existence of discrete NAP foci at mid-cell in cells with two nucleoids, but at cell poles in those with one nucleoid.

Acid Phosphatase↗

Stereolithography versus milled three-dimensional models: comparison of production method, indication, and accuracy.

Computed tomography (CT) based three-dimensional (3-D) lifelike models have proved to be of great value, especially in craniomaxillofacial surgery. They improve and facilitate diagnosis, therapeutic planning, model operations, and definitive treatment in tumor surgery, traumatology, dysgnathia, alveolar atrophy, and congenital and asymmetrical malformations. From 1988 to 1998, 760 stereolithography (STL) and milled 3-D models were employed in our department. These two production methods have become the msot commonly used approaches, and the question as to which is preferable is the subject of controversy in the literature. Using two test models the STL and the milling method were compared with regard to production method and accuracy, and the resulting differences in indications for their use are discussed. The limiting factor for increased accuracy is the distance between each pair of CT scans. Milled models show a higher precision compared to STL models within the CT-scan plane, but the more the measurements deviate from this plane (becoming oblique) the more inaccurate the data becomes. STL exhibits greater deviations, but the inaccuracy is randomly distributed. The mean variation from the original was 0.81 mm for STL and 0.54 mm for milled models. Although 90% of the milled and 80% of the STL values are within a deviation of +/- 1 mm, it should be noted that maximum deviations of 3.15 mm in milled models and 2 mm in STL have been shown. Both methods are sufficiently accurate for clinical use. In standard cases involving the upper and lower jaw, malar bone, orbita, and calvaria the shorter production time and lower costs make milled models preferable. In special cases, in which hollows and fine structures play a major role (e.g., those involving the skull base, paranasal sinuses, inner ear, and mandibular canal), STL is indicated.

Computer Simulation↗

Visual position stabilization in the hummingbird hawk moth, Macroglossum stellatarum L. I. Behavioural analysis.

Optomotor responses of freely flying hawk moths, Macroglossum stellatarum, were characterized while the animals were hovering in front of and feeding on a dummy flower. Compensatory translational and rotational movements of the hawk moth were elicited by vertical grating patterns moving horizontally, mimicking imposed rotational and translational displacements of the animal in the horizontal plane. Oscillatory translational and rotational pattern motion leads to compensatory responses that peak in the frequency range between 2 Hz and 4 Hz. The control systems mediating the translational and rotational components of the optomotor response do not seem to influence each other. The system mediating translational responses is more sensitive in the fronto-lateral part of the visual field than in the lateral part; the opposite is true for the rotational system. The sensitivity of the translational system does not change along the vertical, whereas the rotational system is much more sensitive to motion in the dorsal than in the ventral part of the visual field. These sensitivity gradients may reflect an adaptation to the specific requirements of position stabilization in front of flowers during feeding.

Animals↗