Association of INAD with NORPA is essential for controlled activation and deactivation of Drosophila phototransduction in vivo

Visual transduction in Drosophila is a G protein-coupled phospholipase C-mediated process that leads to depolarization via activation of the transient receptor potential (TRP) calcium channel. Inactivation-no-afterpotential D (INAD) is an adaptor protein containing PDZ domains known to interact with TRP. Immunoprecipitation studies indicate that INAD also binds to eye-specific protein kinase C and the phospholipase C, no-receptor-potential A (NORPA). By overlay assay and site-directed mutagenesis we have defined the essential elements of the NORPA-INAD association and identified three critical residues in the C-terminal tail of NORPA that are required for the interaction. These residues, Phe-Cys-Ala, constitute a novel binding motif distinct from the sequences recognized by the PDZ domain in INAD. To evaluate the functional significance of the INAD-NORPA association in vivo, we generated transgenic flies expressing a modified NORPA, NORPAC1094S, that lacks the INAD interaction. The transgenic animals display a unique electroretinogram phenotype characterized by slow activation and prolonged deactivation. Double mutant analysis suggests a possible inaccessibility of eye-specific protein kinase C to NORPAC1094S, undermining the observed defective deactivation, and that delayed activation may similarly result from NORPAC1094S being unable to localize in close proximity to the TRP channel. We conclude that INAD acts as a scaffold protein that facilitates NORPA-TRP interactions required for gating of the TRP channel in photoreceptor cells.     

Use of a modified non-rebreathing mask during upper intestinal endoscopy

BACKGROUND AND STUDY AIMS: Recently, attention has been drawn to the significant occurrence of respiratory and other complications during upper intestinal endoscopy. This prospective study was designed to compare the incidence and severity of oxygen desaturation when two different methods of oxygen delivery were used during elective oesophagogastroduodenoscopy. PATIENTS AND METHODS: After local medical ethics committee approval and written informed consent, one hundred patients undergoing elective oesophagogastroduodenoscopy were randomly allocated to receive supplemental oxygen at either four litres per minute via nasal specular or ten litres per minute through a specially modified non-rebreathing mask. Oxygen saturations during endoscopy facilitated by midazolam sedation were recorded, and non-parametric tests were used to compare the oxygen saturations in the two groups. RESULTS: The mean oxygen saturations were significantly better during the procedure for American Society of Anesthesiology (ASA) grade 2 and 3 patients who received oxygen with the modified mask than for those who received oxygen via nasal specular (98.6% vs. 97.0%, P = 0.004 for ASA grade 2 and 98.4% vs. 95.5, P = 0.006 for ASA grade 3). CONCLUSIONS: For ASA grade 2 and 3 patients, the modified non-rebreathing mask significantly improves oxygen saturations during upper intestinal endoscopy. This technique should be more widely used for patients at moderate and high risk.     

Middle cerebral artery main stem thrombosis in two siblings with familial thrombotic thrombocytopenic purpura

Idiopathic thrombotic thrombocytopenic purpura (TTP) is frequently complicated by microinfarcts in cerebral cortex and subcortical white matter. We describe two sisters who suffered massive hemispheric infarction due to thrombosis of the middle cerebral artery main stem during exacerbations of TTP. Acute TTP may be associated with intraluminal thrombosis of large-diameter arteries in addition to arterioles and capillaries.     

Inhaled induction and emergence from desflurane anesthesia in the ambulatory surgical patient: the effect of premedication

We studied the effect of premedication (1 microgram/kg fentanyl and 0.04 mg/kg midazolam 5 min before induction of anesthesia) on airway reactivity and hemodynamic stability during inhaled induction using desflurane in 10 ambulatory surgical patients. Eight patients who were anesthetized without premedication served as the controls. Induction and emergence were rapid and unaffected by premedication. End-tidal and inspired concentrations of desflurane at loss of consciousness were significantly reduced by premedication (10.1% end-tidal/14.1% inspired, no premedication, vs. 5.3% end-tidal/8.9% inspired, premedication). Airway irritability was markedly attenuated by premedication (100% no premedication versus 30% premedicated), as was apnea (37.5% no premedication versus 0% premedicated). We observed an increase in mean arterial blood pressure and heart rate after loss of consciousness (mean arterial pressure 103 vs 121 mm Hg, heart rate 73 vs 100 bpm) in the unpremedicated patients, whereas both groups demonstrated a decrease in mean arterial blood pressure with no change in heart rate when baseline values were compared to those at incision (103 vs 74 mm Hg, no premedication, 99 vs 81 mm Hg premedicated). Patient acceptability was satisfactory and unchanged by premedication. We recommend the use of such premedication when desflurane is used during the induction of anesthesia.     

Neuroleptic malignant syndrome and mivacurium: a safe alternative to succinylcholine?

Neuroleptic malignant syndrome (NMS) and malignant hyperthermia (MH) may have a common pathogenic mechanism; therefore, it has been suggested that known triggering agents for MH (such as succinylcholine) should be avoided in patients with NMS. Electroconvulsive therapy (ECT) continues to play a major therapeutic role in contemporary psychiatry, and succinylcholine has been the muscle relaxant of choice in attenuating violent muscle contractions induced by ECT. Mivacurium is a non-depolarizing muscle relaxant with a relatively rapid onset and a short duration of action, and to date it has been proved safe in MH-susceptible patients. In this case report, following succinylcholine use during ECT, a patient with NMS developed an increase in temperature and serum creatine kinase (CK) level, possibly due to an MH reaction. Since the patient's mental status necessitated further ECT, mivacurium was administered during subsequent treatment and resulted in effective attenuation of muscle contractions without elevation of patient temperature or CK levels. In addition, there was no marked prolongation of the anaesthetic. Mivacurium is a suitable agent for patients with NMS undergoing ECT, as it has not been associated with precipitation of an MH response.     

An explanation of disproportionate growth using linear 3-dimensional informetrics and its relation with the fractal dimension

Summary We study new and existing data sets which show that growth rates of sources usually are different from growth rates of items. Examples: references in publications grow with a rate that is different (usually higher) from the growth rate of the publications themselves; article growth rates are different from journal growth rates and so on. In this paper we interpret this phenomenon of “disproportionate growth' in terms of Naranan's growth model and in terms of the self-similar fractal dimension of such an information system, which follows from Naranan's growth model. The main part of the paper is devoted to explain disproportionate growth. We show that the “simple' 2-dimensional informetrics models of source-item relations are not able to explain this but we also show that linear 3-dimensional informetrics (i.e. adding a new source set) is capable to model disproportionate growth. Formulae of such different growth rates are presented using Lotkaian informetrics and new and existing data sets are presented and interpreted in terms of the used linear 3-dimensional model.     

Understanding of the concept of numerically "less" by bottlenose dolphins (Tursiops truncatus).

In 2 experiments, bottlenose dolphins (Tursiops truncatus) judged the ordinal relationship between novel numerosities. The dolphins were first trained to choose the exemplar with the fewer number of items when presented with just a few specific comparisons (e.g., 2 vs. 6, 1 vs. 3, and 3 vs. 7). Generalization of this rule was then tested by presenting the dolphins with all possible pairwise comparisons between 1 and 8. The dolphins chose the exemplar with the fewer number of items at levels far above chance, showing that they could recognize and represent numerosities on an ordinal scale. Their pattern of errors was consistent with the idea of an underlying analog magnitude representation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differentiation of apple juice samples on the basis of heat treatment and variety using chemometric analysis of MIR and NIR data

The potential of mid-infrared (MIR) and near-infrared (NIR) spectroscopy for their ability to differentiate between apple juice samples on the basis of apple variety and applied heat-treatment was evaluated. The heat-treatment involved exposure of juice samples (15 ml) for 30 s in a 900 W microwave oven and the apple varieties used to produce the juice samples were Bramley, Elstar, Golden Delicious and Jonagold. The chemometric procedures applied to the MIR and NIR data were partial least squares regression (PLS1 for differentiation on the basis of heat-treatment, PLS2 for varietal differentiation) and linear discriminant analysis (LDA) applied to principal component (PC) scores. PLS1 and PLS2 gave the highest level of correct classification of the apple juice samples according to heat-treatment (77.2% for both MIR and NIR data) and variety (78.3–100% for MIR data; 82.4–100% for NIR data), respectively.     

Molecular simulation of temperature-programmed desorption

We use accelerated molecular dynamics to probe the thermal desorption of n-alkanes from the Au(1 1 1) and C(0 0 0 1) surfaces. Studying an alkane series ranging from CH₄ to C₁₆H₃₄, we find that the desorption prefactor increases with increasing chain length for the short chains until a certain chain length is reached when it becomes essentially constant and independent of chain length. We can understand the dependence of the preexponential factor on alkane chain length in terms of conformational changes within the alkane molecules. For the shorter molecules, the desorption temperatures probed in experimental temperature-programmed desorption studies lie below those for which torsional motion is activated. Thus, the short alkanes can be treated as rigid rods, and the loss in translational and rotational entropy upon adsorption leads to a preexponential factor that increases with increasing chain length. As the alkane chain length increases, the binding energy and the experimental desorption temperatures also increase. Thus, torsional motion is activated to an extent that increases with increasing chain length. This torsional activation increases the entropy of adsorption and counteracts the entropy decrease due to a loss of translation and rotation. This leads to a virtually constant prefactor for sufficiently long chains. Our findings are consistent with experimental data for the thermal desorption of alkanes from the Au(1 1 1), Pt(1 1 1), MgO(1 0 0) and C(0 0 0 1) surfaces.     

Behavioral and subjective effects of D-amphetamine and modafinil in healthy adults.

Modafinil is indicated for the management of excessive daytime sleepiness; however, recent studies have examined a broad range of potential uses. Given that clinical uses of modafinil may be expanding, this study compared modafinil and d-amphetamine effects on subjective and performance measures. Across 11 sessions, 11 healthy adults were tested after oral doses of placebo (5 sessions), modafinil (1.75 mg/kg, 3.50 mg/kg, or 7.00 mg/kg), and d-amphetamine (0.035 mg/kg, 0.070 mg/kg, 0.140 mg/kg) under double-blind, randomized conditions. Assessments of cognitive performance and subjective effects were completed before drug administration, 30 min after drug administration, and at hourly intervals after drug administration for 5 hr. Modafinil increased ratings on the Amphetamine and Morphine Benzedrine Group scales of the Addiction Research Center Inventory (ARCI) and increased ratings on the Vigor and Total Positive scales of the Profile of Mood States. d-Amphetamine increased visual analog ratings of feeling stimulated and liking the drug and increased ratings on the Morphine Benzedrine Group scale of the ARCI. Both medications significantly reduced visual analog scale ratings of feeling sleepy, and modafinil decreased ratings on the ARCI Pentobarbital-Chlorpromazine-Alcohol Group scale. Both medications sustained performance that deteriorated across time on the Sternberg Number Recognition Test. Modafinil also enhanced performance rate on the Digit-Symbol Substitution Task above baseline levels and increased response rate on the Repeated Acquisition of Response Sequences Task. These results suggest that modafinil engenders alerting effects and increases performance in healthy non-sleep-deprived individuals comparable with that of d-amphetamine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)