Synthesis, spectroscopic, structural and theoretical characterization of hydrogensquarate and mononuclear Au(III)-complex of dipeptide phenylalanyltyrosine

The mononuclear Au(III)-complex ([Au(C₁₈H₁₈N₂O₄)Cl]) and hydrogensquarate ([C₂₂H₂₁N₂O₈]) of dipeptide phenylalanyltyrosine (H–Phe–Tyr–OH) have been synthezised, characterized spectroscopically and structurally by means of solid-state linear-polarized IR-spectroscopy, ¹H- and ¹³C-NMR, ESI-MS, HPLC-MS–MS, FAB-MS, TGS and DSC methods. The structure of the Au(III)-complex has been predicted theoretically by DFT calculations. The dipeptide coordinated in a tridentate manner via –NH₂, –COO⁻ and N⁻-groups. One Cl⁻ ion is attached to the metal centre as a terminal ligand, yielding a planar AuN₂OCl chromophor. The hydrogensquarate consists in positive charged dipeptide moiety and negative one hydrogensquarate (HSq⁻) anion stabilizing by strong intermolecular hydrogen bonds.     

Reactant stationary approximation in enzyme kinetics

In the application of the quasi-steady-state approximation, it is generally assumed that there is an initial transient during which the substrate concentration remains approximately constant while the complex concentration builds up. In this paper, we address the assumption that the substrate concentration does not change significantly during this initial transient and name it the reactant stationary approximation. For the single enzyme, single substrate reaction, the reactant stationary approximation is generally considered a sufficient condition to apply the quasi-steady-state approximation. Studying the dynamic behavior of this reaction with endogenous substrate, we show that the quasi-steady-state approximation and reactant stationary approximation are two separate approximations. We discuss the consequence of this result for the determination of reaction parameters in enzyme catalyzed reactions.     

Introduction to Focus Issue: nonlinear and stochastic physics in biology

Frank Moss was a leading figure in the study of nonlinear and stochastic processes in biological systems. His work, particularly in the area of stochastic resonance, has been highly influential to the interdisciplinary scientific community. This Focus Issue pays tribute to Moss with articles that describe the most recent advances in the field he helped to create. In this Introduction, we review Moss's seminal scientific contributions and introduce the articles that make up this Focus Issue.     

Synchronization analysis of voltage-sensitive dye imaging during focal seizures in the rat neocortex

Seizures are often assumed to result from an excess of synchronized neural activity. However, various recent studies have suggested that this is not necessarily the case. We investigate synchronization during focal neocortical seizures induced by injection of 4-aminopyridine (4AP) in the rat neocortex in vivo. Neocortical activity is monitored by field potential recording and by the fluorescence of the voltage-sensitive dye RH-1691. After removal of artifacts, the voltage-sensitive dye (VSD) signal is analyzed using the nonlinear dynamics-based technique of stochastic phase synchronization in order to determine the degree of synchronization within the neocortex during the development and spread of each seizure event. Results show a large, statistically significant increase in synchronization during seizure activity. Synchrony is typically greater between closer pixel pairs during a seizure event; the entire seizure region is synchronized almost exactly in phase. This study represents, to our knowledge, the first application of synchronization analysis methods to mammalian VSD imaging in vivo. Our observations indicate a clear increase in synchronization in this model of focal neocortical seizures across a large area of the neocortex; a sharp increase in synchronization during seizure events was observed in all 37 seizures imaged. The results are consistent with a recent computational study which simulates the effect of 4AP in a neocortical neuron model.     

Facile synthesis of N-substituted pyrroles via microwave-induced bismuth nitrate-catalyzed reaction

Simple synthesis of N-substituted pyrroles using microwave-induced bismuth nitrate-catalyzed reaction has been accomplished with an excellent yield. A plausible mechanism has been advanced. This reaction also provides a simple method to prepare diverse varieties of N-substituted pyrrole derivatives with less nucleophilic polyaromatic amines.     

Intraindividual variability of striatal (1)H-MRS brain metabolite measurements at 3 T

PURPOSE: To measure possible positional and diurnal physiological effects on brain metabolites in single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) measurements of the right and left striatum. METHODS: (1)H-MRS measurements were performed in 10 healthy adult volunteers using a short echo PRESS sequence (TE=30 ms, TR=3000 ms). Each individual was scanned during both morning and afternoon hours. Regions of interest were right and left striatum. To control for systematic drift in scanner performance, (1)H-MRS measurements of a standard phantom solution were also acquired. Statistical analysis was performed using a repeated measures analysis of variance that included three within-subject factors: metabolite (N-acetyl-aspartate [NAA] or creatine [Cr]), laterality (left or right caudate) and time (morning or afternoon). RESULTS: A significant interaction (P<.016) between time of day and metabolite levels was observed. Further exploration of this finding revealed a significant difference between morning and afternoon levels of NAA (P<.044) but not Cr. In addition, no significant morning-to-afternoon differences were observed for the (1)H-MRS phantom measurements. CONCLUSIONS: Systematic variation due to scanner performance does not account for the changes observed in repeated measurements of striatal NAA levels. This difference may be accounted for by either repositioning effects or circadian physiological effects. Further studies are required to learn whether time of day standardization of (1)H-MRS acquisitions may contribute to improved reproducibility of measurements.     

Progress toward controlling in vivo fibrillating sheep atria using a nonlinear-dynamics-based closed-loop feedback method

We describe preliminary experiments on controlling in vivo atrial fibrillation using a closed-loop feedback protocol that measures the dynamics of the right atrium at a single spatial location and applies control perturbations at a single spatial location. This study allows investigation of control of cardiac dynamics in a preparation that is physiologically close to an in vivo human heart. The spatial-temporal response of the fibrillating sheep atrium is measured using a multi-channel electronic recording system to assess the control effectiveness. In an attempt to suppress fibrillation, we implement a scheme that paces occasionally the cardiac muscle with small shocks. When successful, the inter-activation time interval is the same and electrical stimuli are only applied when the controller senses that the dynamics are beginning to depart from the desired periodic rhythm. The shock timing is adjusted in real time using a control algorithm that attempts to synchronize the most recently measured inter-activation interval with the previous interval by inducing an activation at a time projected by the algorithm. The scheme is "single-sided" in that it can only shorten the inter-activation time but not lengthen it. Using probability distributions of the inter-activation time intervals, we find that the feedback protocol is not effective in regularizing the dynamics. One possible reason for the less-than-successful results is that the controller often attempts to stimulate the tissue while it is still in the refractory state and hence it does not induce an activation. (c) 2002 American Institute of Physics.     

Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice

Background  

Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). We and others have shown that certain NSAIDs reduce secretion of Aβ42 in cell culture and animal models, and that the effect of NSAIDs on Aβ42 is independent of the inhibition of cyclooxygenase by these compounds. Since Aβ42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Aβ42 selectively may be associated with their protective effect. We have previously identified R-flurbiprofen (tarenflurbil) as a selective Aβ42 lowering agent with greatly reduced cyclooxygenase activity that shows promise for testing this hypothesis. In this study we report the effect of chronic R-flurbiprofen treatment on cognition and Aβ loads in Tg2576 APP mice.     

Diastereoselective Ion Pairing of TRISPHAT Anions and Tris(4,4′-dimethyl-2,2′-bipyridine)iron(II)

Two configurationally stable, chiral anions (TRISPHAT, 1 ) behave as efficient hosts that control the configuration of a configurationally labile iron(II ) complex as the guest with high diastereoselectivity (>96 % de) upon ion pairing. The diastereoselectivity increases with decreasing solvent polarity.