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The normal distribution and projections of constitutive NADPH-d/NOS neurons in the brainstem vestibular complex of the rat.

The vestibular system is a highly conserved sensory system in vertebrates that is largely responsible for maintenance of one's orientation in space, posture, and balance and for visual fixation of objects during motion. In light of the considerable literature indicating an involvement of nitric oxide (NO) in sensory systems, it is important to determine whether NO is associated with vestibular pathways. To study the relationship of NO to vestibular pathways, we first examined the normal distribution of constitutive NADPH-diaphorase (NADPH-d), a marker for nitric oxide synthase (NOS), in the vestibular complex (VC) and then examined its association with selected vestibular projection neurons. Survey of the four major vestibular nuclei revealed that only the medial vestibular nucleus contained significant numbers of perikarya stained for NADPH-d/NOS. By contrast, all the vestibular nuclei contained a network of fine processes that stained positive for NADPH-d, although the density of this network varied among the individual nuclei. To determine whether NADPH-d/NOS neurons project to vestibular efferent targets, injections of the retrograde tracer Fluoro-Gold were made into known targets of second-order vestibular neurons. Vestibular neurons containing constitutive NADPH-d/NOS were found to project predominantly to the oculomotor nucleus. A small number of neurons also participate in vestibulothalamic and intrinsic vestibular connections. These results indicate that NADPH-d/NOS neurons are prevalent in the MVN and that a subpopulation of these neurons project to the oculomotor complex. Nitric oxide is probably released locally from axons located throughout the vestibular complex but may play a particularly important role in vestibulo-ocular pathways.

Animals↗

Adjusting for regression toward the mean when variables are normally distributed.

Many studies use the same variable, for example blood pressure in studies of antihypertensive treatments, to identify subjects to be included in the study and to evaluate the effects of a treatment. As a consequence, if not properly accounted for, the effect of regression toward the mean can confound the evaluation of treatment effects if the study has no randomized control group. In this paper we review the methods that have been proposed for adjusting for the effect of regression toward the mean when the variable of interest is assumed to be normally distributed. Maximum likelihood estimation and moment-based estimation are considered, including more recent methods which can be applied when repeated measurements on each subject are available.

Acquired Immunodeficiency Syndrome↗

Axial forces and normal distributed loads in twining stems of morning glory.

In analysing the mechanics of twining, we hypothesize that contact forces are important in maintaining the twining habit of viny stems. This hypothesis is formalized with a description of the force balance in the natural coordinate system associated with the Frenet vectors attached to the 'generative helix' of the vine. The force balance indicates that, if shear forces are neglected, an axial force within the stem is balanced by a normal load distributed along the line of contact between the supporting pole and the stem. Two kinds of empirical studies were conducted to verify the importance of the putative normal load. Firstly, vine geometry was measured on and off the supporting pole. When removed from the pole, the helical stem forms a coil of smaller radius, smaller wavelength and larger torsion. Next, forces were estimated from observations of the pressure exerted by a stem twining around a water-filled balloon. Twining around a dowel 0.95 cm in diameter, a typical stem of morning glory (Pharbitis nil) sustains a tension of 100 g balanced by a normal distributed load of -30 g cm-1. Thus the twining stem puts itself into tension and uses a helical geometry to generate contact forces which are large relative to the stem weight of 40 mg cm-1.

Elasticity↗

LAS24/KOG1, a component of the TOR complex 1 (TORC1), is needed for resistance to local anesthetic tetracaine and normal distribution of actin cytoskeleton in yeast.

It is known that some local anesthetics inhibit the growth of budding yeast cells. To investigate the pathway of local anesthetics' action, we isolated and characterized mutants that were hyper-sensitive to tetracaine, and at the same time, temperature-sensitive for growth. They were collectively called las (local anesthetic sensitive) mutants. One of the LAS genes, LAS24, was found to be identical to KOG1, which had been independently discovered as a member of the TOR complex 1 (TORC1). Las24p/Kog1p is a widely conserved TOR binding protein containing the NRC domain, HEAT repeats and WD-40 repeats, but its function remains unknown. Like the tor mutants, the las24 mutants were found to have a defect in cell wall integrity and to show sensitivity to rapamycin. Furthermore, Las24p is required not only in TORC1-mediated (rapamycin-sensitive) pathways such as translation initiation control and phosphorylation of Npr1p and Gln3p, but also for the normal distribution of the actin cytoskeleton, which has been regarded as a TORC2-mediated event. Intriguingly, the temperature-sensitivity of the las24 mutant was suppressed by either activation of Tap42/PPase or by down-regulation of the RAS/cAMP pathway. Suppressors of the temperature-sensitivity of the las24-1 mutant were found not to be effective for suppression of the tetracaine-sensitivity of the same mutant. These observations along with the facts that tetracaine and high temperature differentially affected the las24-1 mutant suggest that Las24p/Kog1p is not a target of tetracaine and that the tetracaine-sensitive step may be one of downstream branches of the TORC1 pathway. Consistent with the broad cellular functions exerted by the TOR pathway, we found that Las24p was associated with membranes and was localized at vacuoles, the plasma membrane and small vesicles.

Anesthetics, Local↗

Normal distribution of body weight gain in male Sprague-Dawley rats fed a high-energy diet.

OBJECTIVE: To investigate the effect of a high-energy (HE) diet on caloric intake, body weight, and related parameters in outbred male Sprague-Dawley (SD) rats. RESEARCH METHODS AND PROCEDURES: Twenty-eight SD rats were fed either chow (C) for 19 weeks or HE diet for 14 weeks and then C for 5 weeks. Blood hormones and metabolites were assayed, and expression of uncoupling protein-1 and hypothalamic energy-balance-related genes were determined by Northern blotting and in situ hybridization, respectively. RESULTS: HE rats gained body weight more rapidly than C animals with a range of weight gains, but there was no evidence that weight gain was bimodally distributed. Caloric intake was transiently elevated after introduction of the HE diet. Transfer of HE rats back to C resulted in a drop in caloric intake, but a stable body weight. In terminal analysis, two of four dissected adipose tissue depots were heavier in rats that had previously been fed HE diet. Blood leptin, insulin, glucose, and nonesterified fatty acids were not different between the groups. Uncoupling protein-1 mRNA was elevated in interscapular brown adipose tissue from HE rats. There was a trend for agouti-related peptide mRNA in the hypothalamic arcuate nucleus to be higher in HE rats. DISCUSSION: Contrary to other studies of the SD rat on HE diet, body weight and other measured parameters were normally distributed. There was no segregation into two distinct populations on the basis of susceptibility to diet-induced obesity. This characteristic may be dependent on the breeding colony from which animals were sourced.

Adipose Tissue↗

Do QEEG topographic map data have a multivariate normal distribution? Implications for tests of individual maps.

The study was designed to test whether topographic map data expressed in log power units have a multivariate normal (MVN) distribution in a healthy population, and to determine if any deviation from normality poses serious difficulties for the use of standard multivariate statistical tests in assessing the significance of deformations of the map in individual cases. Data on 361 healthy adults using 20 electrodes in the classic 10/20 configuration were recorded in six frequency bands. The log-transformed power data were shown to deviate markedly from MVN. The actual distributions of multivariate tests were computed for the sample using the 'jackknife' method, and shown to deviate markedly from the F-distributions that would be expected for MVN data. These 'jackknife' sampling distributions were then used to demonstrate significant deformations in the topographic maps of a patient who had sustained traumatic head injury.

Adolescent↗

Substance P-containing sensory nerves in the rat iris. Normal distribution, ontogeny and innervation of intraocular iris grafts.

Trigeminal, substance P-containing nerves have been studied in the stretch-prepared rat iris with immunohistochemical techniques. The normal iris exhibited a slightly irregular plexus of individual fibres in the dilator, intermingled with thin, meandering axon bundles. The sphincter contained more circumferentially oriented fibres. Occasional free nerve endings were present in all parts of the iris; no obvious association with blood vessels was detected. All substance P-positive nerves in the iris disappeared after lesioning the trigeminal nerve. Irides of neonates showed scattered, smooth fibres in a sparse plexus, without visible axon bundles. Over the first two postnatal weeks, the density of innervation developed rapidly, reaching a transiently supranormal level and fluorescence intensity, compared to adulthood. From 3 weeks on, the pattern and density of substance P-containing fibres approached the normal adult appearance. In irides grafted to the anterior eye chamber, the intrinsic substance P nerves degenerated, disappearing completely after 5 days. Reinnervation from the host irides transpired over the next few weeks, approximating normal density after 3 weeks, and organotypic density and distribution from 4 weeks on. No obvious hyperinnervation was encountered after longer postoperative times (3 months). In the host iris, many substance P fibres disappear or exhibit low fluorescence intensity during the first postoperative week, recovering fully during the next 2 weeks. Over longer postoperative periods irregular, moderate hyperinnervation developed with increased numbers of axons in bundles. In conclusion, we show normal distribution and plasticity during ontogeny and maturity of substance P-containing iris nerves in the rat, with a sensitive immunohistochemical technique in iris whole mounts.

Animals↗