Biomedical subjects

N M White

Publications and source records attributed to N M White.

At least 19 recordsLinked to original sources

PubMed2006

Investigation of two-dimensional acoustic resonant modes in a particle separator.

Within an acoustic standing wave particles experience acoustic radiation forces, a phenomenon which is exploited in particle or cell manipulation devices. When developing such devices, one-dimensional acoustic characteristics corresponding to the transducer(s) are typically of most importance and determine the primary radiation forces acting on the particles. However, radiation forces have also been observed to act in the lateral direction, perpendicular to the primary radiation force, forming striated patterns. These lateral forces are due to lateral variations in the acoustic field influenced by the geometry and materials used in the resonator. The ability to control them would present an advantage where their effect is either detrimental or beneficial to the particle manipulation process. The two-dimensional characteristics of an ultrasonic separator device have been modelled within a finite element analysis (FEA) package. The fluid chamber of the device, within which the standing wave is produced, has a width to height ratio of approximately 30:1 and it is across the height that a half-wavelength standing wave is produced to control particle movement. Two-dimensional modal analyses have calculated resonant frequencies which agree well with both the one-dimensional modelling of the device and experimentally measured frequencies. However, these two-dimensional analyses also reveal that these modes exhibit distinctive periodic variations in the acoustic pressure field across the width of the fluid chamber. Such variations lead to lateral radiation forces forming particle bands (striations) and are indicative of enclosure modes. The striation spacings predicted by the FEA simulations for several modes compare well with those measured experimentally for the ultrasonic particle separator device. It is also shown that device geometry and materials control enclosure modes and therefore the strength and characteristics of lateral radiation forces, suggesting the potential use of FEA in designing for the control of enclosure modes in similar particle manipulator devices.

Journal Article↗

PubMed2006

Bacterial contamination associated with estuarine shoreline development.

AIMS: To examine the relationships among increasing estuarine shellfish closings due to bacterial contamination, adjacent shoreline land uses and environmental variables. METHODS AND RESULTS: A 1 year study of faecal coliform bacterial contamination of a small estuary in central NC, USA was done relative to adjacent land uses. The area has experienced rapid growth in residential shoreline development including the installation of adjacent, separate docking facilities for larger boats, each <11 slips (pseudomarina) that appear to be a single marina (individual facilities of >10 slips). Six near-shore sites were selected [old developed shore (OD), undeveloped shore (UD), two pseudomarinas (P1, P2), newly developed shore (ND) and a real marina (RM)]. Five locations were spaced along the shore near each site. Paired Thursday/Monday samples were collected biweekly (summer) and monthly (other seasons). Results indicate that OD had the highest bacteria counts followed by ND, RM and P1 & P2. Three sites (OD, ND and RM) failed to meet NC shellfishing waters standards at all locations. At the pseudomarina sites 4 of 10 locations failed to meet shellfish standards while two locations at UD failed to meet these standards. There were no significant differences between paired Thursday/Monday samples. At three sites (OD, UD and P2) bacteria counts were positively correlated with increased water level due to wind tides. CONCLUSIONS: Any type of estuarine shoreline development may result in closing of adjacent shellfishing waters. ND had bacterial counts second only to OD in spite of the retention of vegetated shoreline buffers and very new septic systems. As expected, the RM also failed to meet shellfish standards. Unexpectedly, only four of the 10 pseudomarina locations failed to meet the standards. Weekend boat use had no effect on bacterial counts. Surface runoff from rain and shoreline flooding from increased water levels increased bacterial counts, probably as a result of suspension of surface deposited faeces from wildlife and domestic animals. SIGNIFICANCE AND IMPACT OF THE STUDY: Multiple docking facilities do not necessarily result in violations of shellfish water quality standards. However, the elevated bacterial counts observed along the newly developed shore suggest caution in approving the practice of allowing individual 'oyster gardening' off private piers if the oysters are intended for human consumption. The practice of automatic closure of shellfish waters around RMs was supported. Correlations of bacterial counts with time following significant rainfall suggests a sampling strategy to separate local sources of bacteria from more remote sources thus focusing limited remedial resources more effectively.

Animals↗

PubMed2004

Modelling of particle paths passing through an ultrasonic standing wave.

Within an ultrasonic standing wave particles experience acoustic radiation forces causing agglomeration at the nodal planes of the wave. The technique can be used to agglomerate, suspend, or manipulate particles within a flow. To control agglomeration rate it is important to balance forces on the particles and, in the case where a fluid/particle mix flows across the applied acoustic field, it is also necessary to optimise fluid flow rate. To investigate the acoustic and fluid forces in such a system a particle model has been developed, extending an earlier model used to characterise the 1-dimensional field in a layered resonator. In order to simulate fluid drag forces, CFD software has been used to determine the velocity profile of the fluid/particle mix passing through the acoustic device. The profile is then incorporated into a MATLAB model. Based on particle force components, a numerical approach has been used to determine particle paths. Using particle coordinates, both particle concentration across the fluid channel and concentration through multiple outlets are calculated. Such an approach has been used to analyse the operation of a microfluidic flow-through separator, which uses a half wavelength standing wave across the main channel of the device. This causes particles to converge near the axial plane of the channel, delivering high and low particle concentrated flow through two outlets, respectively. By extending the model to analyse particle separation over a frequency range, it is possible to identify the resonant frequencies of the device and associated separation performance. This approach will also be used to improve the geometric design of the microengineered fluid channels, where the particle model can determine the limiting fluid flow rate for separation to occur, the value of which is then applied to a CFD model of the device geometry.

Journal Article↗

PubMed2000

cato encodes a basic helix-loop-helix transcription factor implicated in the correct differentiation of Drosophila sense organs.

In Drosophila neurogenesis, proneural genes encode bHLH proteins that are required for neural precursor selection. But many vertebrate homologues are expressed later and are postulated to have multiple roles during neurogenesis. We have isolated a new Drosophila gene, cato, which encodes a protein with a bHLH domain that is closely related to that of the proneural protein Atonal. cato expression is restricted to the developing PNS, where it is expressed in between the stages of precursor selection and terminal differentiation (and therefore later than the proneural genes). We present evidence from loss-of-function and misexpression experiments that cato is involved in sensory neurone morphology. Moreover, in prospero mutants, in which axon and dendrite outgrowth is defective, cato is strongly derepressed in the developing CNS.

Amino Acid Sequence↗

PubMed2000

Impaired preference conditioning after anterior temporal lobe resection in humans.

Research with animals suggests that structures within the amygdaloid nuclear complex (ANC) are critical for acquiring associations between rewarding events and neutral stimuli, a form of conditioning often manifested in a subsequent preference for those (conditioned) stimuli. In this study, we investigated the relationship between the ANC and preference learning in humans. Three abstract monochrome patterns were presented to each subject over 180 trials in the context of a counting task requiring working memory. One pattern was paired with food reward on 90% of the trials in which it was presented and with no food reward on the other 10% of trials. The other patterns were similarly reinforced, but at ratios of 50:50% and 10:90% with reward and nonreward, respectively. Subsequently, a group of 21 normal participants preferred the pattern paired most often with reward to that paired least often with reward, and they did not explicitly relate their preferences to the conditioning procedure, but instead attributed them to the characteristics of the patterns themselves. Unlike the normal controls, a group of patients with unilateral surgical lesions that included the ANC (15 left, 18 right) did not show conditioned preferences, but performed normally on a measure of working memory. In contrast, 13 patients with unilateral damage confined to frontal cortex exhibited normal conditioned preferences but were impaired on the working memory task. This double dissociation provides clear evidence that, in humans as in other animals, reward-related learning (conditioned reward) critically depends on a circuit involving inferotemporal cortex and the ANC.

Adolescent↗

PubMed2000

Dorsal hippocampal function in unreinforced spatial learning.

This study examined learning about the spatial environment by rats during a single 10 min period of exploration on an eight-arm radial maze. Because no specific behaviors were learned during this procedure, the existence of learned spatial information was inferred from its retarding effect on subsequent conditioned cue preference (CCP) learning on the same maze. Previous experiments have shown that this form of spatial learning, measured in this way, requires an intact fimbriafornix and functional N-methyl-D-aspartate receptors. However, in the present experiments, large neurotoxic lesions of the dorsal hippocampus that impaired win-shift learning failed to eliminate the retarding effect of exploration on CCP learning. This result was obtained in three independent replications. These findings fail to confirm the hypothesis that the hippocampus is involved in spatial learning when that learning occurs in the absence of reinforcers and does not produce any specific learned behaviors. Previous work showed that this form of "pure" spatial learning requires an intact fimbria-fornix for acquisition but not for expression; the present findings suggest that the hippocampus is not required for either of these processes. The fimbria-fornix may interact with other temporal lobe structures in mediating this form of learning. The function of the hippocampus may be limited in some way to situations that involve reinforcers and/or situations in which specific behaviors are learned.

Animals↗

PubMed2000

Drosophila atonal controls photoreceptor R8-specific properties and modulates both receptor tyrosine kinase and Hedgehog signalling.

During Drosophila eye development, the proneural gene atonal specifies founding R8 photoreceptors of individual ommatidia, evenly spaced relative to one another in a pattern that prefigures ommatidial organisation in the mature compound eye. Beyond providing neural competence, however, it has remained unclear to what extent atonal controls specific R8 properties. We show here that reduced Atonal function gives rise to R8 photoreceptors that are functionally compromised: both recruitment and axon pathfinding defects are evident. Conversely, prolonged Atonal expression in R8 photoreceptors induces defects in inductive recruitment as a consequence of hyperactive EGFR signalling. Surprisingly, such prolonged expression also results in R8 pattern formation defects in a process associated with both Hedgehog and Receptor Tyrosine Kinase signalling. Our results strongly suggest that Atonal regulates signalling and other properties of R8 precursors.

Animals↗

PubMed1999

Parallel information processing in the dorsal striatum: relation to hippocampal function.

We investigated the effects of localized medial and lateral CPu lesions and fornix/fimbria lesions on responses to a local cue and to behavior based on cognitive-spatial information in the water maze. Rats were trained concurrently on the cue (visible platform) and spatial (submerged platform) components of the task, followed by a test in which responses to the two types of information were dissociated by a measure of competing response tendencies. Bilateral lesions of lateral CPu did not affect acquisition of either cue or spatial responding but produced a preference for the spatial response on the competition test. Bilateral lesions of the medial CPu retarded but did not prevent learning both components and produced a preference for the cue response on the competition test. The latter effect was accompanied by increased thigmotaxis (swimming in the periphery of the pool), primarily during the early acquisition trials, which was attributed to an impaired ability to respond to learned spatial information. Fornix/fimbria lesions prevented spatial but not cue learning and produced a preference for the cue response on the competition test. Asymmetric lesions (unilateral hippocampus and contralateral medial CPu) produced mild retardation of acquisition of both the cue and spatial tasks and a preference for the cue response on the competition test. These findings dissociate the functions of the lateral and medial CPu and suggest that the hippocampus and medial CPu may be parts of a system that promotes responding based on learned cognitive-spatial information, particularly in competitive cue-place response situations.

Analysis of Variance↗

PubMed1999

Effects of medial and lateral caudate-putamen lesions on place- and cue-guided behaviors in the water maze: relation to thigmotaxis.

Rats with dorsomedial or dorsolateral caudate-putamen lesions and sham-operated controls were trained on the standard hidden platform (place) task in the water maze. Compared to controls, rats with dorsomedial, but not dorsolateral lesions were slower to escape to the hidden platform and spent significantly more time swimming near the wall of the pool (thigmotaxis) on the early trials, but eventually achieved control levels of performance. When the platform was removed from the pool, all groups exhibited a significant bias for swimming in the training quadrant and crossing the former location of the platform. In the second phase of the experiment rats were given visible platform (cue) training in a different room/pool with the platform moved to a new location each day. Rats with dorsomedial, but not dorsolateral lesions required more trials to reach criterion; again, thigmotaxis was observed on the early trials. The third phase, carried out in the original room/pool, included a place-retention trial followed by a place-cue competition test, (i.e. a choice between the learned spatial location of the hidden platform and the visible platform in a new location). The rats with dorsomedial, but not dorsolateral lesions swam to the visible platform more frequently than the controls. In the final phase, the rats in both lesion groups exhibited slightly lower thigmotactic tendencies than controls in a standard dry-land open field, a finding inconsistent with the hypothesis that thigmotaxis in the water maze is due to increased fear or anxiety. Taken together with other behavioral and anatomical findings, the results suggest that the dorsomedial caudate-putamen, by virtue of its connections with limbic and prefrontal cortical regions, may mediate a response selection process that integrates cognitive information with stimulus-response tendencies.

Animals↗

PubMed1999

Progesterone and prostaglandin H synthase-2 involvement in alcohol-induced preterm birth in mice.

BACKGROUND: Recently, an association between alcohol consumption during pregnancy and shortened gestational length has been reported, but the underlying mechanisms remain unknown. Progesterone (P4) and prostaglandins have been shown to play important roles in parturition in both human and animal models. Recently, it has been suggested that prostaglandin H synthase-2 (PGHS-2) is responsible for prostaglandin changes associated with term and preterm labor. It is possible that alcohol induces preterm birth by altering P4 or PGHS-2 levels. These studies were designed to determine the role of P4 and PGHS-2 in alcohol-induced preterm labor in mice. METHODS: Experiment 1: Pregnant dams treated with either vehicle or alcohol (6 g/kg, intragastrically) on gestational day (GD) 16 were killed at various times in gestation up to the time of delivery. Plasma P4 levels were measured by radioimmunoassay and uterine PGHS-2 mRNA expression was measured by Ribonuclease Protection Assay. Results indicated that alcohol treatment was associated with an earlier decline in plasma P4 levels and an earlier rise in uterine PGHS-2 mRNA levels during gestation. Experiment 2: Pregnant C57BL/6J females were treated with either P4 (2.0 mg, subcutaneously) or vehicle (sesame oil) 2 hr before receiving either 6 g/kg alcohol (intragastrically) or vehicle (isocaloric sucrose) on gestational day (GD) 16. Results indicate that P4 pretreatment effectively antagonized alcohol-induced preterm delivery. Experiment 3: On GD16, pregnant dams received either 100 mg/kg nimesulide (a specific PGHS-2 inhibitor) or vehicle (saline) subcutaneously, 2 hr before treatment with either 6 g/kg alcohol (given intragastrically) or isocaloric sucrose. Nimesulide was effective in antagonizing alcohol-induced preterm labor. CONCLUSIONS: Together, these data suggest that both P4 and PGHS-2 may play roles in alcohol-induced preterm birth.

Animals↗

PubMed1998

Preferential localization of self-stimulation sites in striosomes/patches in the rat striatum.

Histological sections of the mammalian striatum reveal a "matrix" that is histochemically distinguishable from patches, or "striosomes". The latter are cross sections of a compartment that consists primarily of tube-shaped structures radiating through the matrix. As a test of the hypothesis that the function of the striosome/patch compartment includes the mediation of behaviors related to reward, the present study examined electrical self-stimulation of the caudoputamen in rats with electrodes in either of the two compartments. Rats acquired and maintained bar-pressing responses that were contingent on stimulation through electrodes making contact with striosomes/patches more reliably than animals with electrodes terminating exclusively in the matrix. The results provide in vivo evidence that the striosome/patch compartment is functionally differentiated from the matrix compartment: Stimulation centered in or around the striosome/patch compartment but not in the matrix led to rapid acquisition of a new behavior.

Animals↗

PubMed1998

Selective hippocampal lesions yield nonspatial memory impairments in rhesus monkeys.

Monkeys with removals of medial temporal lobe (MTL) structures are widely recognized as valid models of human global anterograde amnesia, a syndrome that arises consequent to damage to a finite set of brain structures situated in the medial temporal lobe and/or medial diencephalon. However, a comparison of memory deficits in human and nonhuman primates with MTL damage has presented a long-standing puzzle. Whereas amnesic patients are impaired in learning object discrimination problems, monkeys with MTL damage are typically not. One possible explanation for this difference is that object discrimination tasks for humans and monkeys differ in that the former but not the latter requires the use of contextual information. If this analysis is correct, monkeys with MTL damage might be disadvantaged in learning to discriminate similar objects presented in different contexts. To test this possibility, we evaluated the effects of excitotoxic lesions of one of the MTL structures, the hippocampus, on the rate of learning of discrimination problems embedded within unique contexts. Monkeys with hippocampal lesions were impaired relative to controls in learning object discrimination problems of this type. These findings strongly support the idea that the difference in the effect on object memory of MTL damage in human and nonhuman primates is due to a difference in the opportunity to employ contextual cues rather than to a difference in the organization of memory.

Animals↗

PubMed1998

Contributions of the hippocampus, amygdala, and dorsal striatum to the response elicited by reward reduction.

Rats were trained to run down a runway for either 1 or 10 food pellets. After training, those receiving 10 pellets were shifted to 1 pellet. Such shifts typically elicit a temporary decrease in running speed. Groups of normal rats and rats with bilateral lesions of the fimbria-fornix, lateral-basolateral complex of the amygdala, or dorsal striatum were tested with the shifted and unshifted procedures. Separate experiments, identical except for the intertrial intervals (ITIs; 3 min vs. 30 s), were carried out. The data are consistent with the view that an integrated action of multiple neural systems is required to observe the typical response to reward reduction in unlesioned rats. One system that includes the dorsal striatum promotes a reinforced approach response to the goal box. A neural system that includes fimbria-fornix is required to retain information about reduced reward over the 3-min ITI. A system that includes the amygdala may acquire a conditioned aversive response to the goal box after the shift is detected, leading to reduced speeds over testing.

Amygdala↗

PubMed1997

Systematic comparison of the effects of hippocampal and fornix-fimbria lesions on acquisition of three configural discriminations.

The effects of lesions to the hippocampal system on acquisition of three different configural tasks by rats were tested. Lesions of either the hippocampus (kainic acid/colchicine) or fornix-fimbria (radiofrequency current) were made before training. After recovery from surgery, rats were trained to discriminate between simple and compound-configural cues that signaled the availability or nonavailability of food when a bar was pressed. When positive cues were present, one food pellet could be earned by pressing a lever after a variable time had elapsed. The trial terminated on food delivery (variable interval 15 s). This procedure eliminates some possible alternative explanations of the results of previous experiments on configural learning. Hippocampal lesions increased rates of responding and retarded acquisition of a negative patterning task (A+, B+, AB-); using a ratio measure of discrimination performance these lesions had a milder retarding effect on a biconditional discrimination (AX+, AY-, BY+, BX-), and they had no effect on a conditional context discrimination (X: A+, B-; Y: A-, B+). Fornix-fimbria lesions did not affect acquisition of any of these tasks but increased rates of responding. The results suggest that several task parameters determine the involvement of the hippocampus in configural learning; however, all tasks tested can also be learned to some extent in the absence of an intact hippocampal system, presumably by other learning/memory systems that remain intact following surgery. The lack of effect of fornix-fimbria lesions on any of these tasks suggests that retrohippocampal connections with other brain areas may mediate hippocampal contributions to the learning of some configural tasks. An analysis of these results and of experiments on spatial learning situations suggests that involvement of the hippocampus is a function of the degree to which correct performance depends on a knowledge of relationships among cues in a situation.

Animals↗

PubMed1997

Roles of movement and temporal factors in spatial learning.

Previous experiments suggested that rats can learn to discriminate between adjacent arms of an eight-arm radial maze if they have an intact hippocampal system and are allowed to move around on the maze. These requirements are consistent with the hypothesis that this discrimination involves hippocampus-based spatial learning. We examined the importance of self-generated movement in this form of learning by moving rats manually ("passive movement") between two adjacent maze arms within a single training trial. Rats moved passively between arms (only one of which contained food) within trials learned to discriminate between the arms, as measured by a conditioned preference for the food arm when both arms were empty. This form of learning was impaired by lesions of fimbria-fornix, but was unaffected by lesions of the lateral nucleus of the amygdala. Normal rats that were picked up and replaced on the same arm within trials and experienced their food and no food arms on different daily trials failed to learn the same discrimination. These findings suggest that self-generated movement is not required for spatial learning that may be mediated by a hippocampal system; rather, movement may simply serve to provide information from different locations about the cues in an environment.

Amygdala↗

PubMed1997

Dopamine D3 receptor mutant mice exhibit increased behavioral sensitivity to concurrent stimulation of D1 and D2 receptors.

The dopamine D3 receptor is expressed primarily in regions of the brain that are thought to influence motivation and motor functions. To specify in vivo D3 receptor function, we generated mutant mice lacking this receptor. Our analysis indicates that in a novel environment, D3 mutant mice are transiently more active than wild-type mice, an effect not associated with anxiety state. Moreover, D3 mutant mice exhibit enhanced behavioral sensitivity to combined injections of D1 and D2 class receptor agonists, cocaine and amphetamine. However, the combined electrophysiological effects of the same D1 and D2 agonists on single neurons within the nucleus accumbens were not altered by the D3 receptor mutation. We conclude that one function of the D3 receptor is to modulate behaviors by inhibiting the cooperative effects of postsynaptic D1 and other D2 class receptors at systems level.

Amphetamine↗

PubMed1997

Mnemonic functions of the basal ganglia.

A synthesis of older and recent work on mnemonic functions of the basal ganglia in rats, monkeys and humans emphasizes a reciprocal relationship of the caudate nucleus and putamen with the cerebral cortex, which mediates the memory of consistent relationships between stimuli and responses (sometimes called habits) that often involve relationships between the individual and its environment (egocentric memory). Evidence at several levels of analysis (including neuroplastic synaptic changes, activity of single neurons, and behavioral changes caused by lesions or neurochemical manipulations) implicate dopamine release from nigro-striatal neurons in the reinforcement, or strengthening, of neural representations in the basal ganglia.

Animals↗

PubMed1997

Cloning and characterization of three Musca domestica yolk protein genes.

The yolk protein (yp) genes encode the major nutritional polypeptides deposited in developing oocytes for subsequent utilization during embryogenesis, and represent a highly conserved family of genes in higher Diptera. Originally isolated from Drosophila melanogaster, they are expressed in a temporal-, tissue- and sex-specific manner in all species in which they have been identified. We report here the isolation of cDNAs encoding three independent yolk proteins from the common housefly, Musca domestica. Expression of the three M. domestica yp genes is analysed both by Northern and in-situ hybridization. We discuss in an evolutionary context both the significance of the expression patterns, and regions of apparent polypeptide sequence divergence.

Amino Acid Sequence↗