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.     

Lake morphometry determines Dreissena invasion dynamics

Predicting the ecosystem effects of invasive species and the best control strategies requires understanding population dynamics and population regulation. Invasive bivalves zebra and quagga mussels (Dreissena spp.) are considered the most aggressive invaders in freshwaters and have become major drivers of ecosystem processes in the Laurentian Great Lakes. Combining all lake-wide studies of Dreissena spp. conducted in the Great Lakes, we found that invasion dynamics are largely governed by lake morphometry. Where both species are present, quagga mussels generally become dominant in 8–13 years. Thereafter, zebra mussels remain common in shallow lakes and embayments and lake-wide Dreissena density may remain similar, while in deep lakes quagga led to a near-complete displacement of zebra mussels and an ensuing dramatic increase in overall dreissenid density. In deep lakes, overall Dreissena biomass peaked later and achieved?~?threefold higher levels than in shallow lakes. Comparison with 21 waterbodies in North America and Europe colonized by both dreissenids confirmed that patterns of invasion dynamics found in the Great Lakes are very consistent with other waterbodies, and thus can be generalized to other lakes. Our biophysical model predicted that the long-term reduction in primary producers by mussel grazing may be fourfold less in deep compared to shallow lakes due to thermal stratification and a smaller proportion of the epilimnion in contact with the bottom. While this impact remains greatest in shallow areas, we show that when lakes are vertically well-mixed, dreissenid grazing impact may be greatest offshore, revealing a potentially strong offshore carbon and phosphorus sink.

     

PHARMACOLOGICAL STUDIES ON THE STIMULATION OF THE PHOSPHOLIPASE A2-ACYLATION SYSTEM OF SYNAPTIC MEMBRANES OF BRAIN, BY NEUROTRANSMITTERS AND OTHER AGONISTS

Methacholine, nicotine and succinylcholine stimulated the phospholipase A2-acylation system of synaptic membranes isolated from the cerebral cortex of guinea pig. Stimulation by acetylcholine was partially blocked by atropine and by D-tuberocurarine respectively, indicating both muscarinic and nicotinic stimulation. Muscarinic stimulation by acetylcholine was greater than -isotinic stimulation, and stimulation by acetylcholine was completely blocked by a combip, or;. and n-tuberocurarine. The phospholipase A2-acylat tem was stimulated by phenylcphrine., id. Cqxoterenoi. Stimulation by noradrenaline was J-. tidlr, by phenoxybenzamine and pindalol i:spectively, indicating both 8-adrenergic and P-adrenergic ztimulation. n-Adrenergic stimulation by noradrenaline was greater than P-adrenergic-stimulation. 5 -mlation by noradrenaline was completely blocked by a combination of phenoxybenzamins and pindalol. Stimulation of both acylation and phospholipid hydrolysis, by 5-hydroxytryptamine and histamine were partially blocked by methysergide and diphenhydramine respectively. Stimulation by dopamine was blocked by halopcridol. Stimulation by y-aminobutyric acid was partially blocked by strychnine and by picrotoxin. Dichloroisoproterenol, atropine, methysergidr, diphenhydramine, strychnine, picrotoxin and eserine, at relatively high concentrations (1 mM), stimuhted the phospholipase A2-acylation system. Synergistic stimulations of both acylatior, and hydrolysis of phosphatidylcholine, were observed by adenosine combined with noradrenaline, 5-hydroxytryptamine, histamine, dopamine or yaminobutyric acid, respectively. In the presence of ATP-MgCI, synergistic stimulations of the hydrolysis of phosphatidyicholine were observed after 30 s by noradrenaline combined with 5-hydroxytryptamine, histamine, dopamine, aminobutyric acid or carbamoylcholine respectively. In the presence of GTP-MgC12 synergistic stimulations were obtained by cdrbamoylcholine combined with noradrenaline. 5-hydroxytryptamine. histamine, dopamine or y-aminobutyric acid, respectively. In the presence of ATP-MgC12 plus GTP-MgC12, stimulation by noradrenaline and one other agonist including 5-hydroxytryptamine, histamine, dopamine, y-aminobutyric acid or carbamoylcholine were close to additive.     

Effects of random and non-random errors on phenotypic selection in autotetraploids

Summary A theoretical investigation was made to ascertain the effects of random and non-random deviations, called errors, of phenotypic from genotypic values on population means and on the response to phenotypic recurrent selection. The study was motivated as a selection experiment for disease resistance where there was either variability in the inoculation or environment (the random errors) or where the inoculation was above or below the the optimum rate where genetic differences in resistance are maximized (the non-random errors). The study was limited to the genetics at a diallelic locus (alleles B and b) in an autotetraploid population in random mating equilibrium. The response to selection was measured as the covariance of selection and compared to the exact covariance which was the covariance of selection without errors in phenotype. The random errors were modeled by assuming that a given percentage () of the population was uniformly distributed among the five possible genotype classes independent of their true genotypes. This model was analyzed numerically for a theoretical population with the frequency of the B allele (p) ranging from 0.0 to 1.0 and assumed errors of=0.1 and 0.5 for the following six types of genic action of the B allele: additive, monoplex dominance, partial monoplex dominance, duplex dominance, partial duplex dominance, and recessive. The effect of random error was to consistently reduce the response to selection by a percentage independent of the type of genic action at the locus. The effect on the population mean was an upward bias when p was low and a downward bias when p approached unity. In the non-random error model below optimum inoculations altered the phenotypes by systematically including percentage of susceptible genotypes into one or more other genotype classes with more genetic resistance (a positive shift). With above optimum inoculations, some resistant genotypes are classed with the non-resistant genotypes (a negative shift). The effects on the covariance of selection were found by numerical analysis for the same types of genic action and's as investigated for random error. With a negative shift and a low p, the covariance of selection was always reduced, but for an increasing p the covariance approached and exceeded the exact covariance for all types of genic action except additive. With a positive shift and a low p, response to selection was greatly improved for three types of genic action: duplex dominance, partial duplex dominance, and recessive. The effect of a non-random error on population means was to greatly bias the means upwards for a low p and positive shift, but with increasing p the bias decreased. A relatively slight decrease in the mean occurred with a negative shift. This study indicated check varieties commonly used to monitor selection pressures in screening programs are very responsive to positive non-random shifts, but are relatively unresponsive to negative shifts. The interaction of selection pressure, types of genic action, and genotypes in the class shift models was suggested as a partial explanation for the lack of response to increasing selection pressures observed in some breeding programs.Cooperative investigations of the Alfalfa Production Research Unit, United States Department of Agriculture, Agricultural Research Service, and the Nevada Agricultural Experiment Station, Reno, Nevada. Paper No. 404 Scientific Journal Series. Nevada Agricultural Experiment Station     

Method for Quantitative Study of Airway Functional Microanatomy Using Micro-Optical Coherence Tomography

We demonstrate the use of a high resolution form of optical coherence tomography, termed micro-OCT (μOCT), for investigating the functional microanatomy of airway epithelia. μOCT captures several key parameters governing the function of the airway surface (airway surface liquid depth, periciliary liquid depth, ciliary function including beat frequency, and mucociliary transport rate) from the same series of images and without exogenous particles or labels, enabling non-invasive study of dynamic phenomena. Additionally, the high resolution of μOCT reveals distinguishable phases of the ciliary stroke pattern and glandular extrusion. Images and functional measurements from primary human bronchial epithelial cell cultures and excised tissue are presented and compared with measurements using existing gold standard methods. Active secretion from mucus glands in tissue, a key parameter of epithelial function, was also observed and quantified.     

Critical determinants of the interactions of capsule-expressing Neisseria meningitidis with host cells: the role of receptor density in increased cellular targeting via the outer membrane Opa proteins

Neisseria meningitidis capsule is an important virulence determinant required for survival in the blood but is reportedly involved in inhibiting cellular interactions mediated by meningococcal outer membrane adhesins. However, evidence from our previous studies suggested that target receptor density on host cells may determine whether or not capsulate bacteria can adhere via outer membrane proteins such as Opa. To confirm this and evaluate the impact of capsulation on bacterial interactions, we used Opa(+) and Opa(-) derivatives of capsulate and acapsulate meningococcal isolates and transfected cell lines expressing CEACAM1, a receptor targeted by Opa proteins. To assess the extent and rate of cell association, subpopulations of stably transfected Chinese hamster ovary cells with different receptor levels were derived. A quantitative correlation of CEACAM1 levels and Opa-dependent binding of both capsulate and acapsulate bacteria was demonstrated, which was accelerated at high receptor densities. However, it appears that invasion by Opa(+) capsulate bacteria only occurs when a threshold level of CEACAM density has been reached. Target cells expressing high levels of CEACAM1 (MFI c. 400) bound threefold more, but internalized 20-fold more Opa(+) capsulate bacteria than those with intermediate expression (MFI c. 100). No overall selection of acapsulate phenotype was observed in the internalized population. These observations confirm that capsule may not be an adequate barrier for cellular interactions and demonstrate the role of a host factor that may determine capsulate bacterial invasion potential. Upregulation of CEACAMs, which can occur in response to inflammatory cytokines, could lead to translocation of a small number of fully capsulate bacteria across mucosal epithelium into the bloodstream sufficient to cause a rapid onset of disseminated disease. Thus the data also suggest a novel rationale for the epidemiological observations that individuals with prior infectious/inflammatory conditions carry a high risk of invasive meningococcal disease.     

Virulence of Salmonella enteritidis phage type 4 is related to the possession of a 38 MDa plasmid

Nine strains of Salmonella enteritidis phage type 4 were examined for virulence in BALB/c mice. The possession of a 38 MDa plasmid was necessary for full virulence. Strains carrying this plasmid had LD50 values of less than 20 bacteria whilst plasmid-free strains had LD50 values of greater than 10(6) bacteria when challenged intraperitoneally. Pathogenesis of disease involved the widespread distribution of bacteria throughout the tissues. Possession of the 38 MDa plasmid could not be linked with the ability of strains to express novel outer membrane proteins, to produce toxins affecting Vero, Y1, HeLa, Henle or HEp-2 cells, or to invade HEp-2 cells. Furthermore, the 38 MDa plasmid did not encode an aerobactin-mediated iron uptake system or the production of a haemolysin. Strains of S. enteritidis PT4 isolated in 1967, 1978 or 1979 and possessing the 38 MDa plasmid showed the same virulence properties as the current plasmid-carrying strains. This suggests that the enhanced virulence of the current strains for poultry is unlikely to be the result of changes in the 38 MDa plasmid.