Biomedical subjects

Markus Meister

Publications and source records attributed to Markus Meister.

9 recordsLinked to original sources

PubMed2006

The molecular architecture of the metalloprotease FtsH.

The ATP-dependent integral membrane protease FtsH is universally conserved in bacteria. Orthologs exist in chloroplasts and mitochondria, where in humans the loss of a close FtsH-homolog causes a form of spastic paraplegia. FtsH plays a crucial role in quality control by degrading unneeded or damaged membrane proteins, but it also targets soluble signaling factors like sigma(32) and lambda-CII. We report here the crystal structure of a soluble FtsH construct that is functional in caseinolytic and ATPase assays. The molecular architecture of this hexameric molecule consists of two rings where the protease domains possess an all-helical fold and form a flat hexagon that is covered by a toroid built by the AAA domains. The active site of the protease classifies FtsH as an Asp-zincin, contrary to a previous report. The different symmetries of protease and AAA rings suggest a possible translocation mechanism of the target polypeptide chain into the interior of the molecule where the proteolytic sites are located.

Adenosine Triphosphatases↗

PubMed2006

Online guideline assist in intensive care medicine--is the login-authentication a sufficient trigger for reminders?

INTRODUCTION: Rising cost pressure due to the implementation of the DRG-System and quality assurance lead to an increased use of therapy standards and standard operating procedures (SOPs) in intensive care medicine. The intention of the German Scientific Society supported project "OLGA" (Online Guideline Assist) is to develop a prototype of a knowledge based system supporting physicians of an intensive care unit in recognizing the indication for and selecting a specific guideline or SOP. While the response of the prototype on user entries can be displayed as a signal on the used workstation itself, the location and time for a reminder of scheduled or missed procedures or reactions to imported information is a difficult issue. One possible approach to this task is the display of non acknowledged reminders or recommendations while logging on to a system. The objective of this study is to analyse user behaviour of the physicians working on the surgical intensive care unit to decide whether the login authentication is a sufficient trigger for clinical reminding. METHODS: The surgical intensive care unit examined in this study comprises 14 beds. Medical care is provided by physicians working in shifts 24 hours a day, 7 days a week, with two anaesthetists at a time and an additional senior consultant during daytime. The entire documentation (examinations, medication, orders, care) is performed using the patient data management system ICUData. The authentication process of the physicians was logged and analysed. RESULTS: Throughout the observation period from December 13th 2005 to January 11th 2006 3563 physician logins were counted in total. The mean span between logins was in 11.3 minutes (SD 14.4), the median 7 minutes. The 75% centile was 14 minutes, the 95% centile 38 min. Intervals greater than 60 minutes occurred in 75%, and greater than 90 minutes in 25% of the days. DISCUSSION: It seems reasonable that reminders sent during authentication are able to enforce workflow compliance. It is possible to send notifications caused by external events to the physician depending on the importance of the event. Serious events with high urgency should be reliably passed using wireless pager or handheld technology. It seems that after the implementation of the prototype guideline assist further investigation is needed to monitor changes in authentication behaviour and reactions to the guideline advisory. This is also required to investigate the influence of unit's size, medical specialty and actual ward workload.

Critical Care↗

PubMed2005

Dynamic predictive coding by the retina.

Retinal ganglion cells convey the visual image from the eye to the brain. They generally encode local differences in space and changes in time rather than the raw image intensity. This can be seen as a strategy of predictive coding, adapted through evolution to the average image statistics of the natural environment. Yet animals encounter many environments with visual statistics different from the average scene. Here we show that when this happens, the retina adjusts its processing dynamically. The spatio-temporal receptive fields of retinal ganglion cells change after a few seconds in a new environment. The changes are adaptive, in that the new receptive field improves predictive coding under the new image statistics. We show that a network model with plastic synapses can account for the large variety of observed adaptations.

Adaptation, Physiological↗

PubMed2004

Retina versus cortex; contrast adaptation in parallel visual pathways.

Human vision adapts to the contrast of patterns by changing its sensitivity, but the origins of this perceptual adaptation have been disputed. In this issue of Neuron, Solomon et al. show that contrast adaptation in the primate arises mostly in the retina for the magnocellular pathway and mostly in the cortex for the parvocellular pathway. It appears that adaptation arises most strongly at sites that pool over many inputs.

Adaptation, Biological↗

PubMed2003

Genetically engineered mice with an additional class of cone photoreceptors: implications for the evolution of color vision.

Among eutherian mammals, only primates possess trichromatic color vision. In Old World primates, trichromacy was made possible by a visual pigment gene duplication. In most New World primates, trichromacy is based on polymorphic variation in a single X-linked gene that produces, by random X inactivation, a patchy mosaic of spectrally distinct cone photoreceptors in heterozygous females. In the present work, we have modeled the latter strategy in a nonprimate by replacing the X-linked mouse green pigment gene with one encoding the human red pigment. In the mouse retina, the human red pigment seems to function normally, and heterozygous female mice express the human red and mouse green pigments at levels that vary between animals. Multielectrode array recordings from heterozygous female retinas reveal significant variation in the chromatic sensitivities of retinal ganglion cells. The data are consistent with a model in which these retinal ganglion cells draw their inputs indiscriminately from a coarse-grained mosaic of red and green cones. These observations support the ideas that (i) chromatic signals could arise from stochastic variation in inputs drawn nonselectively from red and green cones and (ii) tissue mosaicism due to X chromosome inactivation could be one mechanism for driving the evolution of CNS diversity.

Action Potentials↗

PubMed2003

Segregation of object and background motion in the retina.

An important task in vision is to detect objects moving within a stationary scene. During normal viewing this is complicated by the presence of eye movements that continually scan the image across the retina, even during fixation. To detect moving objects, the brain must distinguish local motion within the scene from the global retinal image drift due to fixational eye movements. We have found that this process begins in the retina: a subset of retinal ganglion cells responds to motion in the receptive field centre, but only if the wider surround moves with a different trajectory. This selectivity for differential motion is independent of direction, and can be explained by a model of retinal circuitry that invokes pooling over nonlinear interneurons. The suppression by global image motion is probably mediated by polyaxonal, wide-field amacrine cells with transient responses. We show how a population of ganglion cells selective for differential motion can rapidly flag moving objects, and even segregate multiple moving objects.

Action Potentials↗

PubMed2003

Multineuronal firing patterns in the signal from eye to brain.

Population codes in the brain have generally been characterized by recording responses from one neuron at a time. This approach will miss codes that rely on concerted patterns of action potentials from many cells. Here we analyze visual signaling in populations of ganglion cells recorded from the isolated salamander retina. These neurons tend to fire synchronously far more frequently than expected by chance. We present an efficient algorithm to identify what groups of cells cooperate in this way. Such groups can include up to seven or more neurons and may account for more than 50% of all the spikes recorded from the retina. These firing patterns represent specific messages about the visual stimulus that differ significantly from what one would derive by single-cell analysis.

Action Potentials↗

PubMed2002

Fast and slow contrast adaptation in retinal circuitry.

The visual system adapts to the magnitude of intensity fluctuations, and this process begins in the retina. Following the switch from a low-contrast environment to one of high contrast, ganglion cell sensitivity declines in two distinct phases: a fast change occurs in <0.1 s, and a slow decrease over approximately 10 s. To examine where these modulations arise, we recorded intracellularly from every major cell type in the salamander retina. Certain bipolar and amacrine cells, and all ganglion cells, adapted to contrast. Generally, these neurons showed both fast and slow adaptation. Fast effects of a contrast increase included accelerated kinetics, decreased sensitivity, and a depolarization of the baseline membrane potential. Slow adaptation did not affect kinetics, but produced a gradual hyperpolarization. This hyperpolarization can account for slow adaptation in the spiking output of ganglion cells.

Adaptation, Ocular↗

PubMed2002

Loss of sex discrimination and male-male aggression in mice deficient for TRP2.

The mouse vomeronasal organ (VNO) is thought to mediate social behaviors and neuroendocrine changes elicited by pheromonal cues. The molecular mechanisms underlying the sensory response to pheromones and the behavioral repertoire induced through the VNO are not fully characterized. Using the tools of mouse genetics and multielectrode recording, we demonstrate that the sensory activation of VNO neurons requires TRP2, a putative ion channel of the transient receptor potential family that is expressed exclusively in these neurons. Moreover, we show that male mice deficient in TRP2 expression fail to display male-male aggression, and they initiate sexual and courtship behaviors toward both males and females. Our study suggests that, in the mouse, sensory activation of the VNO is essential for sex discrimination of conspecifics and thus ensures gender-specific behavior.

Aggression↗