The stimulation by transmitter substances and putative transmitter substances of the net activity of phospholipase A2 of synaptic membranes of cortex of guinea-pig brain.

1. The distribution of the hydrolyses of phosphatidylcholine by phospholipase A2 and phospholipase A1, and the hydrolysis of lysophosphatidylcholine by lysophospholipase, in subcellular and subsynaptosomal fractions of cerebral cortices of guinea-pig brain, was determined. 2. Noradrenaline stimulated hydrolysis by phospholipase A2 in whole synaptosomes, synaptic membranes and fractions containing synaptic vesicles. 3. Stimulation of hydrolysis by phospholipase A2 in synaptic membranes by noradrenaline was enhanced by CaCl2, and by a mixture of ATP and MgCl2. The optimum concentration of CaCl2, in the presence of ATP and MgCl2, for stimulation by 10 muM-noradrenaline was in the range 1-10muM. The optimum concentration for ATP-2MgCl2 in the presence of 1 muM-CaCl2 was in the range 0.1-1mM. 4. Hydrolysis by phospholipase A2 of synaptic membranes was also stimulated by acetylcholine, carbamoylcholine, 5-hydroxytryptamine, dopamine (3,4-dihydroxyphenethylamine), histamine, psi-aminobutyric acid, glutamic acid and aspartic acid. With appropriate concentrations of cofactors, sigmoidal dose-response curves were obtained, half-maximum stimulations being obtained with concentrations of stimulant in the range 0.1-1muM. 5. Taurine also stimulated hydrolysis of phosphatidylcholine by phospholipase A2. There were only slight stimulations with methylamine, ethylenediamine or spermidine. No stimulation was obtained with glucagon.     

Evaluation of late results of surgical treatment of congenital heart disease.

Operative mortality from surgical treatment of congenital heart disease has been steadily reduced over the past 20 years. During the same period it has become clear that a proportion of survivors have residual clinical problems. Some of these are due to imperfect repair, a number being due to factors beyond present surgical control, and some are the consequence of associated cardiovascular defects. The chief problems can be elucidated by an analysis of the results of surgical treatment of six cardiac malformations: simple pulmonary valve stenosis, coarctation of the aorta, secundum atrial septal defect, isolated ventricular septal defect, tetralogy of Fallot and transposition of the great arteries. Recognition of the sequelae of preoperative hemodynamic strain and apparently minor associated malformations is important, and it is possible to anticipate such factors. Long-term follow-up of patients after operation is particularly important.     

Measurement of Outflow Facility Using iPerfusion

Elevated intraocular pressure (IOP) is the predominant risk factor for glaucoma, and reducing IOP is the only successful strategy to prevent further glaucomatous vision loss. IOP is determined by the balance between the rates of aqueous humour secretion and outflow, and a pathological reduction in the hydraulic conductance of outflow, known as outflow facility, is responsible for IOP elevation in glaucoma. Mouse models are often used to investigate the mechanisms controlling outflow facility, but the diminutive size of the mouse eye makes measurement of outflow technically challenging. In this study, we present a new approach to measure and analyse outflow facility using iPerfusion^™, which incorporates an actuated pressure reservoir, thermal flow sensor, differential pressure measurement and an automated computerised interface. In enucleated eyes from C57BL/6J mice, the flow-pressure relationship is highly non-linear and is well represented by an empirical power law model that describes the pressure dependence of outflow facility. At zero pressure, the measured flow is indistinguishable from zero, confirming the absence of any significant pressure independent flow in enucleated eyes. Comparison with the commonly used 2-parameter linear outflow model reveals that inappropriate application of a linear fit to a non-linear flow-pressure relationship introduces considerable errors in the estimation of outflow facility and leads to the false impression of pressure-independent outflow. Data from a population of enucleated eyes from C57BL/6J mice show that outflow facility is best described by a lognormal distribution, with 6-fold variability between individuals, but with relatively tight correlation of facility between fellow eyes. iPerfusion represents a platform technology to accurately and robustly characterise the flow-pressure relationship in enucleated mouse eyes for the purpose of glaucoma research and with minor modifications, may be applied in vivo to mice, as well as to eyes from other species or different biofluidic systems.     

Widespread Triploidy in Western North American Aspen (Populus tremuloides)

We document high rates of triploidy in aspen (Populus tremuloides) across the western USA (up to 69% of genets), and ask whether the incidence of triploidy across the species range corresponds with latitude, glacial history (as has been documented in other species), climate, or regional variance in clone size. Using a combination of microsatellite genotyping, flow cytometry, and cytology, we demonstrate that triploidy is highest in unglaciated, drought-prone regions of North America, where the largest clone sizes have been reported for this species. While we cannot completely rule out a low incidence of undetected aneuploidy, tetraploidy or duplicated loci, our evidence suggests that these phenomena are unlikely to be significant contributors to our observed patterns. We suggest that the distribution of triploid aspen is due to a positive synergy between triploidy and ecological factors driving clonality. Although triploids are expected to have low fertility, they are hypothesized to be an evolutionary link to sexual tetraploidy. Thus, interactions between clonality and polyploidy may be a broadly important component of geographic speciation patterns in perennial plants. Further, cytotypes are expected to show physiological and structural differences which may influence susceptibility to ecological factors such as drought, and we suggest that cytotype may be a significant and previously overlooked factor in recent patterns of high aspen mortality in the southwestern portion of the species range. Finally, triploidy should be carefully considered as a source of variance in genomic and ecological studies of aspen, particularly in western U.S. landscapes.     

The effect of fluoxetine on warfarin metabolism in the rat and man.

Fluoxetine, a selective blocker of serotonin uptake, inhibits the metabolism of warfarin in rats. In contrast, after a single dose or seven daily doses of fluoxetine to human subjects, no inhibition of warfarin metabolism was observed.     

Probing,Assessment and Management during Interactions between Ground Squirrels (Rodentia: Sciuridae) and Rattlesnakes (Squamata: Viperidae). 2: Cues Afforded by Rattlesnake Rattling

The predator-prey relationship between California ground squirrels (Spermophilus beecheyi) and northern Pacific rattlesnakes (Crotalus riridis oreganus) is a useful system in which to explore risk assessment and management. Rattlesnakes are major predators of ground-squirrel pups, but pose only a sublethal threat to adult squirrels. Adults approach, harass, and even attack rattlesnakes when confronted with them. A rattlesnake's response to such harassment can include rattling and striking. Not all rattlesnakes pose the same risk to an adult squirrel. Larger, warmer rattlesnakes strike in ways that may be more effective at overwhelming the defensive leaps of squirrels, and larger snakes can inject more venom if they are successful in landing a bite. It would therefore benefit squirrels to assess and respond appropriately to rattlesnakes of different body size and temperature. We looked for cues in rattling upon which such assessments might be based. We recorded and digitally analyzed the rattling sounds of snakes of different sizes, each tested at four different body temperatures — 10, 18, 27, and 35°C. Results indicate that warmer snakes rattle with faster click rates, higher amplitudes, and shorter latencies. Similarly, larger snakes produce rattling sounds of higher amplitude and lower dominant frequencies. Thus, rattling provides reliable cues about rattlesnake dangerousness. Nevertheless, this highly ‘informative’ characteristic of rattling has its origins in physical and physiological constraints, not in specialization for communication. Ground squirrels appear to probe for the information extractable from rattling, for example by pushing loose substrate at the snake and thus inducing it to rattle. Future reports will discuss the degree to which ground squirrels actually exploit these cues.