Shaping of IPSCs by endogenous calcineurin activity

Synaptic inhibition, mediated by GABAA receptors, regulates neuronal firing, influences coincidence detection (K?nig et al., 1996), and can synchronize the output of neural circuits (Cobb et al., 1995). Although GABAA receptors can be modulated by phosphorylation, few studies have directly addressed the role of such modulation at synapses, where the nonequilibrium conditions of receptor activation are quite different from those often used to study GABAA receptors in vitro. Here we promoted endogenous phosphorylation by inhibiting specific phosphatases in rat hippocampal neurons and compared the effects on IPSCs with GABAA channel responses in outside-out patches. Brief and saturating GABA pulses (5 msec; 10 mM) activated patch currents resembling the IPSC. Inhibition of calcineurin (protein phosphatase 2B), but not phosphatases 1 or 2A, produced a similar shortening of IPSC and patch responses, as did nonspecific inhibition of dephosphorylation using ATPgammaS or high concentrations of intracellular phosphate. Calcineurin inhibition increased the microscopic ligand unbinding rate, which was measured using the competitive antagonist 2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl)pyridazinium bromide, suggesting that the IPSC shortening was partly caused by destabilization of the ligand binding site. Calcineurin inhibition also increased the rate and extent of macroscopic receptor desensitization. These results show that endogenous regulation by kinases and calcineurin can produce substantial changes in the IPSC duration by altering the unbinding and gating kinetics of the GABAA receptor. Dynamic regulation of synaptic inhibition may thus allow for the tuning of circuit behavior at the level of individual inhibitory synapses.     

Ventilatory and lactate threshold determinations in healthy normals and cardiac patients: methodological problems

In healthy normal individuals (n = 69), coronary patients with myocardial ischaemia (n = 27) and patients with chronic heart failure (CHF, n = 33), four widely applied methods to determine ventilatory threshold (VT) were analysed: V-slope, ventilatory equivalent for O2 (EqO2), gas exchange ratio (R) and end-tidal partial pressure of oxygen. Lactate threshold [LAT, log lactate vs log oxygen uptake (VO2)] was also determined. Analysis focused on rate of success of threshold determination, comparability of threshold methods, reproducibility and interobserver variability. Cycle ergometry protocols with ramp-like mode and graded steady-state mode used in exercise testing were considered separately. In healthy normal individuals and coronary patients with myocardial ischaemia, at least three VT could be determined during ramp-like mode and two VT during graded steady-state mode, 82% of the time. For CHF patients, the rate of successful determination of VT was lower. Compared to LAT, VO2 at VT was significantly higher using R and EqO2 methods of VT determination in healthy normal subjects (P < 0.01), and significantly higher when using all four methods in coronary patients (P < 0.01 or P < 0.05, respectively). No difference was observed between VO2 at VT and LAT in CHF patients. In healthy normal individuals, day-to-day reproducibility of VT and LAT was high (error of a single determination from duplicate determinations was between 3.9% and 6.2% corresponding to a VO2 of 52.2 and 89.2 ml.min-1). Interobserver variability was low (error between 0.3% and 5% corresponding to a VO2 of 9.8 and 68 ml.min-1). In CHF patients, interobserver variability was moderately greater (error between 4.6% and 8.2%, corresponding to a VO2 of 35.1 and 62.4 ml.min-1). To optimize threshold determination, standardized procedures are suggested.     

The Nucleic Acid Database: Present and Future

The Nucleic Acid Database is a relational database containing information about three-dimensional nucleic acid structures. The methods used for data processing, structure validation, database management and information retrieval, as well as the various services available via the World Wide Web, are described. Plans for the future include greater reliance on the Macromolecular Crystallographic Information File for both data processing and data management.     

Proactive, motivationally enhanced smoking cessation counseling among women with elevated cervical cancer risk.

Current treatment guidelines recommend that all smokers be given motivational or action-oriented counseling, as is appropriate to their readiness to quit smoking. The present study assessed the acceptability and impact of a proactively delivered, motivationally tailored phone counseling program targeted to women with elevated risk for cervical cancer. Female smokers with a recent abnormal pap exam or a colposcopy were contacted and invited to participate, regardless of their interest in quitting smoking. Participants were randomly assigned to usual care (UC) or UC plus motivationally enhanced phone counseling (MEC). The intervention was well received: 79% of eligible women enrolled (n = 275), and 90% completed at least three of four calls. Participation did not vary by baseline motivation to quit. Compared with control subjects, counseling participants were more likely to seek additional treatment services and had a higher 7-day point-prevalence abstinence rate at 6 months (20% MEC vs. 12% UC, p<.05). MEC impact was sustained at 12 months, but abstinence increased among the UC group (18% MEC vs. 20% UC, p = ns). There was no difference in repeated point-prevalence abstinence at 6 and 12 months (11% MEC vs. 10% UC, p = ns). Outcomes were similar in a subgroup of 229 women who, at baseline, were interested in quitting in the next 6 months.     

Extinction and latent inhibition of within-event learning are context specific.

Exposure to a solution composed of an odor (almond) and a taste (salt) produced a context-independent preference when rats were subsequently tested with almond under a salt appetite. Postcompound exposure to either the almond or the salt alone reduced almond preferences but only when rats were tested in the extinction context. Exposure to either the almond or the salt in 1 context in advance of exposure to the compound in a different context also reduced preferences but only when the rats were tested in the context in which the element had been pre-exposed. These results show that extinction and latent inhibition of within-event learning are context specific. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An oscillator circuit to produce a radio-frequency discharge and application to metastable helium saturated absorption spectroscopy

We present a rf gas discharge apparatus which provides an atomic frequency reference for laser manipulation of metastable helium. We discuss the biasing and operation of a Colpitts oscillator in which the discharge coil is part of the oscillator circuit. Radiofrequency radiation is reduced by placing the entire oscillator in a metal enclosure.     

Aeroelastic applications of the Connection Machine

This paper describes the implementation of a dynamical systems approach to aeroelastic analysis using the Connection Machine model 2 (CM-2). Through numerical simulation, the regions of harmonic and chaotic behavior in the δ,R_x (velocity, in-plane load) plane have been examined in detail. These regions are of interest in evaluation of the fatigue life of fluttering plates. The CM-2 computer architecture allows the removal of many of the previous simplifying and limiting assumptions regarding the prediction of the stability regions maps. Owing to its high-speed prediction capability, the CM-2, with framebuffer, offers 'real-time' display of the solution as it evolves during the prediction process. This feature gives insight into the fundamental way in which the solution evolves. This is essential in defining the scenarios describing roads to chaotic behavior of the dissipative dynamical systems.