Melatonin and the time window for the expression of the alpha 8 nicotinic acetylcholine receptor in the membrane of chick retinal cells in culture

We have previously shown that melatonin influences the development of alpha 8 nicotinic acetylcholine receptor (nAChR) by measurement of the acetylcholine-induced increase in the extracellular acidification rate (ECAR) in chick retinal cell cultures. Cellular differentiation that takes place between DIV (days in vitro) 4 and DIV 5 yields cells expressing alpha 8 nAChR and results in a significant increase in the ECAR acetylcholine-induced. Blocking melatonin receptors with luzindole for 48 h suppresses the development of functional alpha 8 nAChR. Here we investigated the time window for the effect of melatonin on retinal cell development in culture, and whether this effect was dependent on an increase in the expression of alpha 8 nAChR. First, we confirmed that luzindole was inhibiting the effects of endogenous melatonin, since it increases 2-[(125)I] iodomelatonin (23 pM) binding sites density in a time-dependent manner. Then we observed that acute (15, 60 min, or 12 h) luzindole treatment did not impair acetylcholine-induced increase in the ECAR mediated by activation of alpha 8 nAChR at DIV 5, while chronic treatment (from DIV 3 or DIV 4 till DIV 5, or DIV 3.5 till DIV 4.5) led to a time-dependent reduction of the increase in the acetylcholine-induced ECAR. The binding parameters for [(125)I]-alpha-bungarotoxin (10 nM) sites in membrane were unaffected by melatonin suppression that started at DIV 3. Thus, melatonin surges in the time window that occurs at the final stages of chick retinal cell differentiation in culture is essential for development of the cells expressing alpha 8 nAChR subtype in full functional form. (C) 2010 ISDN. Published by Elsevier Ltd. All rights reserved.

Discontinuous local semiflows for Kurzweil equations leading to LaSalle`s invariance principle for differential systems with impulses at variable times

In this paper, we consider an initial value problem for a class of generalized ODEs, also known as Kurzweil equations, and we prove the existence of a local semidynamical system there. Under certain perturbation conditions, we also show that this class of generalized ODEs admits a discontinuous semiflow which we shall refer to as an impulsive semidynamical system. As a consequence, we obtain LaSalle`s invariance principle for such a class of generalized ODEs. Due to the importance of LaSalle`s invariance principle in studying stability of differential systems, we include an application to autonomous ordinary differential systems with impulse action at variable times. (C) 2011 Elsevier Inc. All rights reserved.

Large amplitude oscillations for a class of symmetric polynomial differential systems in R³

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Robust State-Derivative Feedback LMI-Based Designs for Linear Descriptor Systems

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Sufficients conditions for analysis of extrema in the step-response of the linear control systems

This note deals whith the problem of extrema which may occur in the step-response of a stable linear system with real zeros and poles. Some simple sufficients conditions and necessary conditions are presented for analyses when zeros located between the dominant and fastest pole does not cause extrema in the step-response. These conditions require knowledge of the pole-zero configuration of the corresponding transfer-function.

Limit Cycles for a Class of Continuous and Discontinuous Cubic Polynomial Differential Systems

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Darboux invariants for planar polynomial differential systems having an invariant conic

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Limit cycles of cubic polynomial differential systems with rational first integrals of degree 2

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Normal Forms for Polynomial Differential Systems in R-3 Having an Invariant Quadric and a Darboux Invariant

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Nerve fiber layer in glaucomatous hemifield loss: a case-control study with time- and spectral-domain optical coherence tomography

Purpose: To evaluate the retinal nerve fiber layer measurements with time-domain (TD) and spectral-domain (SD) optical coherence tomography (OCT), and to test the diagnostic ability of both technologies in glaucomatous patients with asymmetric visual hemifield loss. Methods: 36 patients with primary open-angle glaucoma with visual field loss in one hemifield (affected) and absent loss in the other (non-affected), and 36 age-matched healthy controls had the study eye imaged with Stratus-OCT (Carl Zeiss Meditec Inc., Dublin, California, USA) and 3 D OCT-1000 (Topcon, Tokyo, Japan). Peripapillary retinal nerve fiber layer measurements and normative classification were recorded. Total deviation values were averaged in each hemifield (hemifield mean deviation) for each subject. Visual field and retinal nerve fiber layer "asymmetry indexes" were calculated as the ratio between affected versus non-affected hemifields and corresponding hemiretinas. Results: Retinal nerve fiber layer measurements in non-affected hemifields (mean [SD] 87.0 [17.1] mu m and 84.3 [20.2] mu m, for TD and SD-OCT, respectively) were thinner than in controls (119.0 [12.2] mu m and 117.0 [17.7] mu m, P<0.001). The optical coherence tomography normative database classified 42% and 67% of hemiretinas corresponding to non-affected hemifields as abnormal in TD and SD-OCT, respectively (P=0.01). Retinal nerve fiber layer measurements were consistently thicker with TD compared to SD-OCT. Retinal nerve fiber layer thickness asymmetry index was similar in TD (0.76 [0.17]) and SD-OCT (0.79 [0.12]) and significantly greater than the visual field asymmetry index (0.36 [0.20], P<0.001). Conclusions: Normal hemifields of glaucoma patients had thinner retinal nerve fiber layer than healthy eyes, as measured by TD and SD-OCT. Retinal nerve fiber layer measurements were thicker with TD than SD-OCT. SD-OCT detected abnormal retinal nerve fiber layer thickness more often than TD-OCT.

The time window for generation of dendritic spikes by coincidence of action potentials and EPSPs is layer specific in somatosensory cortex

The precise timing of events in the brain has consequences for intracellular processes, synaptic plasticity, integration and network behaviour. Pyramidal neurons, the most widespread excitatory neuron of the neocortex have multiple spike initiation zones, which interact via dendritic and somatic spikes actively propagating in all directions within the dendritic tree. For these neurons, therefore, both the location and timing of synaptic inputs are critical. The time window for which the backpropagating action potential can influence dendritic spike generation has been extensively studied in layer 5 neocortical pyramidal neurons of rat somatosensory cortex. Here, we re-examine this coincidence detection window for pyramidal cell types across the rat somatosensory cortex in layers 2/3, 5 and 6. We find that the time-window for optimal interaction is widest and shifted in layer 5 pyramidal neurons relative to cells in layers 6 and 2/3. Inputs arriving at the same time and locations will therefore differentially affect spike-timing dependent processes in the different classes of pyramidal neurons.

Safety of endovascular treatment beyond the 6-h time window in 205 patients

Background and purpose Intra-arterial treatment (IAT) is effective when performed within 6 h of symptom onset in selected stroke patients (‘T < 6H’). Its safety and efficacy is unclear when the patient has had symptoms for more than 6 h (‘T > 6H’) or for an unknown time (unclear-onset stroke, UOS), or woke up with a stroke (wake-up stroke, WUS). In this study we compared the safety of IAT in these four patient groups. Methods Eight-hundred and fifty-nine patients treated with IAT were enrolled. The main outcome parameters were clinical outcome [excellent: modified Rankin Scale (mRS) 0 or 1; or favorable: mRS 0–2] or mortality 3 months after treatment. Further outcome parameters were the rates of vessel recanalization, and cerebral and systemic hemorrhage. Results Six-hundred and fifty-four patients were treated before (T < 6H) and 205 after 6 h or an unknown time (128 T > 6H, 55 WUS and 22 UOS). NIHSS scores were higher in UOS patients than in T < 6H patients, vertebrobasilar occlusion was more common in T > 6H and UOS patients, and middle cerebral artery occlusions less common in T > 6H than in T < 6H patients. Other baseline characteristics were similar. There was no significant difference in clinical outcome and the rate of hemorrhage in multivariable regression analysis. Conclusions Clinical outcome of our four groups of patients was similar with no increase of hemorrhage rates in patients treated after awakening, after an unknown time or more than 6 h. Our preliminary data suggest that treatment of such patients may be performed safely. If confirmed in randomized trials, this would have major clinical implications.

Two-dimensional grayscale ultrasound and spectral Doppler waveform evaluation of dogs with chronic enteropathies

Sonography is an important diagnostic tool to examine the gastrointestinal tract of dogs with chronic diarrhea. Two-dimensional grayscale ultrasound parameters to assess for various enteropathies primarily focus on wall thickness and layering. Mild, generalized thickening of the intestinal wall with maintenance of the wall layering is common in inflammatory bowel disease. Quantitative and semi-quantitative spectral Doppler arterial waveform analysis can be utilized for various enteropathies, including inflammatory bowel disease and food allergies. Dogs with inflammatory bowel disease have inadequate hemodynamic responses during digestion of food. Dogs with food allergies have prolonged vasodilation and lower resistive and pulsatility indices after eating allergen-inducing foods.

Time window for recanalization in basilar artery occlusion: Speculative synthesis.

Basilar artery occlusion (BAO) is one of the most devastating forms of stroke and few patients have good outcomes without recanalization. Most centers apply recanalization therapies for BAO up to 12-24 hours after symptom onset, which is a substantially longer time window than the 4.5 hours used in anterior circulation stroke. In this speculative synthesis, we discuss recent advances in BAO treatment in order to understand why and under which circumstances longer symptom duration might not necrotize the brainstem and turn therapeutic attempts futile. We raise the possibility that distinct features of the posterior circulation, e.g., highly developed, persistent collateral arterial network, reverse filling of the distal basilar artery, and delicate plasma flow siding the clot, might sustain brittle patency of brainstem perforators in the face of stepwise growth of the thrombus. Meanwhile, the tissue clock characterizing the rapid necrosis of a typical anterior circulation penumbra will not start. During this perilous time period, recanalization at any point would salvage the brainstem from eventual necrosis caused by imminent reinforcement and further building up of the clot.

Linear and nonlinear pathways of spectral information transmission in the cochlear nucleus

At the level of the cochlear nucleus (CN), the auditory pathway divides into several parallel circuits, each of which provides a different representation of the acoustic signal. Here, the representation of the power spectrum of an acoustic signal is analyzed for two CN principal cells—chopper neurons of the ventral CN and type IV neurons of the dorsal CN. The analysis is based on a weighting function model that relates the discharge rate of a neuron to first- and second-order transformations of the power spectrum. In chopper neurons, the transformation of spectral level into rate is a linear (i.e., first-order) or nearly linear function. This transformation is a predominantly excitatory process involving multiple frequency components, centered in a narrow frequency range about best frequency, that usually are processed independently of each other. In contrast, type IV neurons encode spectral information linearly only near threshold. At higher stimulus levels, these neurons are strongly inhibited by spectral notches, a behavior that cannot be explained by level transformations of first- or second-order. Type IV weighting functions reveal complex excitatory and inhibitory interactions that involve frequency components spanning a wider range than that seen in choppers. These findings suggest that chopper and type IV neurons form parallel pathways of spectral information transmission that are governed by two different mechanisms. Although choppers use a predominantly linear mechanism to transmit tonotopic representations of spectra, type IV neurons use highly nonlinear processes to signal the presence of wide-band spectral features.