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Biomedical subjects

F Moss

Publications and source records attributed to F Moss.

At least 19 recordsLinked to original sources

Human autoantibodies specific for the alpha1A calcium channel subunit reduce both P-type and Q-type calcium currents in cerebellar neurons.

The pharmacological properties of voltage-dependent calcium channel (VDCC) subtypes appear mainly to be determined by the alpha1 pore-forming subunit but, whether P-and Q-type VDCCs are encoded by the same alpha1 gene presently is unresolved. To investigate this, we used IgG antibodies to presynaptic VDCCs at motor nerve terminals that underlie muscle weakness in the autoimmune Lambert-Eaton myasthenic syndrome (LEMS). We first studied their action on changes in intracellular free Ca2+ concentration [Ca2+]i in human embryonic kidney (HEK293) cell lines expressing different combinations of human recombinant VDCC subunits. Incubation for 18 h with LEMS IgG (2 mg/ml) caused a significant dose-dependent reduction in the K+-stimulated [Ca2+]i increase in the alpha1A cell line but not in the alpha1B, alpha1C, alpha1D, and alpha1E cell lines, establishing the alpha1A subunit as the target for these autoantibodies. Exploiting this specificity, we incubated cultured rat cerebellar neurones with LEMS IgG and observed a reduction in P-type current in Purkinje cells and both P- and Q-type currents in granule cells. These data are consistent with the hypothesis that the alpha1A gene encodes for the pore-forming subunit of both P-type and Q-type VDCCs.

Animals

Noise-induced spiral waves in astrocyte syncytia show evidence of self-organized criticality.

Long range (a few centimeters), long lived (many seconds), spiral chemical waves of calcium ions (Ca2+) are observed in cultured networks of glial cells for normal concentrations of the neurotransmitter kainate. A new method for quantitatively measuring the spatiotemporal size of the waves is described. This measure results in a power law distribution of wave sizes, meaning that the process that creates the waves has no preferred spatial or temporal (size or lifetime) scale. This power law is one signature of self-organized critical phenomena, a class of behaviors found in many areas of science. The physiological results for glial networks are fully supported by numerical simulations of a simple network of noisy, communicating threshold elements. By contrast, waves observed in astrocytes cultured from human epileptic foci exhibited radically different behavior. The background random activity, or "noise", of the network is controlled by the kainate concentration. The mean rate of wave nucleation is mediated by the network noise. However, the power law distribution is invariant, within our experimental precision, over the range of noise intensities tested. These observations indicate that spatially and temporally coherent Ca2+ waves, mediated by network noise may play and important role in generating correlated neural activity (waves) over long distances and times in the healthy vertebrate central nervous system.

Astrocytes

Effect of nerve block on sural amplitude during remote muscle contraction.

We previously reported that the median sensory nerve action potentials (SNAPs) increased in amplitude during both near (3) and remote (4) muscle contraction. The objective of the present project was to begin to study the pathway by which this occurred. The sural amplitude was measured after one min. of isometric biceps contraction and compared pre and post lidocaine nerve block in 10 healthy subjects. The baseline was defined as the least amount of current needed to elicit a minimal sural response pre contraction. This level of stimulus remained constant throughout the experiment. Results showed that the sural amplitude peaked 4 min. after muscle contraction. An 8.1 microV increase in sural amplitude from baseline was noted pre injection as 5 min. post contraction, and an increase of 13.4 microV was noted comparing pre to post injection amplitudes at the same time. Statistical analysis using two-way interaction comparing the time courses pre and post injection showed a 92% chance the responses were dissimilar Post hoc least significant difference (LSD) analyses were significant at 4 min. (p = .005) and 6 min. (p = 0.29) post contraction. In conclusion, the increase in sural amplitude after remote muscle contraction was no longer apparent after proximal sural nerve block. This suggests that the nerve itself is required in the final common pathway for the transmission of this induced signal.

Action Potentials

Association of use of a log book and experience as a preregistration house officer: interview survey.

OBJECTIVE: To determine whether use of a log book improved the experiences of preregistration house officers. DESIGN: Confidential questionnaire and interview survey of preregistration house officers carried out as part of University of London inspection process. MEASURES: Preregistration house officers were asked to rate educational and pastoral elements of their posts and about the use made of previously distributed log books. SUBJECTS AND SETTING: Preregistration house officers in North Thames. RESULTS: The incumbents of 535 of 560 (95%) preregistration house officer posts in the region were surveyed between June 1994 and July 1995, 490 by questionnaire and interview, 45 by questionnaire alone. House officers who had discussed the log book with their consultant expressed more satisfaction with their induction, consultant supervision and feedback, and formal and informal education and were more likely to recommend their job to a friend. CONCLUSION: Preregistration house officers who had discussed the log book with their consultant expressed more satisfaction with the educational elements of their jobs. The structured discussion with their consultant about the job and their performance seemed to make the difference.

Consultants

Low-dimensional dynamics in sensory biology. 1: Thermally sensitive electroreceptors of the catfish.

We report the results of a search for evidence of periodic unstable orbits in the electroreceptors of the catfish. The function of these receptor organs is to sense weak external electric fields. In addition, they respond to the ambient temperature and to the ionic composition of the water. These quantities are encoded by receptors that make use of an internal oscillator operating at the level of the membrane potential. If such oscillators have three or more degrees of freedom, and at least one of which also exhibits a nonlinearity, they are potentially capable of chaotic dynamics. By detecting the existence of stable and unstable periodic orbits, we demonstrate bifurcations between noisy stable and chaotic behavior using the ambient temperature as a parameter. We suggest that the technique developed herein be regarded as an additional tool for the analysis of data in sensory biology and thus can be potentially useful in studies of functional responses to external stimuli. We speculate that the appearance of unstable orbits may be indicative of a state of heightened sensory awareness by the animal.

Animals

Characterization of low-dimensional dynamics in the crayfish caudal photoreceptor.

Attempts to detect and characterize chaos in biological systems are of considerable interest, especially in medical science, where successful demonstrations may lead to new diagnostic tools and therapies. Unfortunately, conventional methods for identifying chaos often yield equivocal results when applied to biological data, which are usually heavily contaminated with noise. For such applications, a new technique based on the detection of unstable periodic orbits holds promise. Infinite sets of unstable periodic orbits underlie chaos in dissipative systems; accordingly, the new method searches a time series only for rare events characteristic of these unstable orbits, rather than analysing the structure of the series as a whole. Here we demonstrate the efficacy of the method when applied to the dynamics of the crayfish caudal photoreceptor (subject to stimuli representative of the animal's natural habitat). Our findings confirm the existence of low-dimensional dynamics in the system, and strongly suggest the existence of deterministic chaos. More importantly, these results demonstrate the power of methods based on the detection of unstable periodic orbits for identifying low-dimensional dynamics--and, in particular, chaos--in biological systems.

Action Potentials

Detecting low dimensional dynamics in biological experiments.

We discuss the well-known problems associated with efforts to detect and characterize chaos and other low dimensional dynamics in biological settings. We propose a new method which shows promise for addressing these problems, and we demonstrate its effectiveness in an experiment with the crayfish sensory system. Recordings of action potentials in this system are the data. We begin with a pair of assumptions; that the times of firings of neural action potentials are largely determined by high dimensional random processes or "noise"; and that most biological files are non stationary, so that only relatively short files can be obtained under approximately constant conditions. The method is thus statistical in nature. It is designed to recognize individual "events" in the form of particular sequences of time intervals between action potentials which are the signatures of certain well defined dynamical behaviors. We show that chaos can be distinguished from limit cycles, even when the dynamics is heavily contaminated with noise. Extracellular recordings from the crayfish caudal photoreceptor, obtained while hydrodynamically stimulating the array of hair receptors on the tailfan, are used to illustrate the method.

Action Potentials