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Biomedical subjects

H R Wilson

Publications and source records attributed to H R Wilson.

At least 19 recordsLinked to original sources

In vivo antitumor activity and metabolism of a series of 5-deazaacyclotetrahydrofolate (5-DACTHF) analogues.

This study compares the antitumor activity and metabolism of the purine de novo biosynthesis inhibitor 5-deazaacyclotetrahydrofolate and a series of analogues. All compounds have similar IC50 values for inhibition of MCF-7 cell growth, activity of glycineamide ribonucleotide transformylase, and methotrexate uptake by MOLT-4 cells, the latter a measure of cellular uptake potential. Only 5-deazaacyclotetrahydrofolate and the 2'-fluoro and 3'-fluoro analogues demonstrated significant inhibition of colon 38 adenocarcinoma or HCT-116 colon carcinoma growth in vivo. This correlated with the Km of these compounds for folylpolyglutamate synthetase. 5-Deazaacyclotetrahydrofolate and 2'-fluoro-5-deazaacyclotetrahydrofolate which displayed the strongest antitumor activity were detectable in colon 38 tumor tissue 24 hr after dosing and were present nearly exclusively as the polyglutamated species. These results indicate that polyglutamation represents a critical step in the in vivo antitumor activity of these compounds.

Acyltransferases

Perceived direction of moving two-dimensional patterns depends on duration, contrast and eccentricity.

Type II two-dimensional motion is produced by superimposing two one-dimensional drifting cosine gratings with velocity vectors lying on the same side of the intersection-of-constraints (IOC) resultant. When type II patterns were constructed with components having the same spatial frequency and contrast, perceived direction was found to be biased toward the vector sum direction at short durations and approached the direction predicted by IOC only after some time lag. This time lag was contrast dependent. At 5% contrast, the perceived direction after 1 sec of presentation remained biased by more than 20 degrees. Direction perception was also measured at 15 degrees eccentricity. At this eccentricity the perceived direction of type II patterns was grossly biased away from the IOC prediction in the direction of the component vectors by an average of 25 degrees.

Contrast Sensitivity

Moving two-dimensional patterns can capture the perceived directions of lower or higher spatial frequency gratings.

Coherent plaid motion is produced by superimposing two one-dimensional gratings of the same spatial frequency moving +/- 60 degrees from the intersection-of-constraints (IOC) resultant direction. These moving plaids were found to change the perceived direction of a third one-dimensional grating, either 6-fold lower or higher in spatial frequency, from traveling in one of the plaid's component direction to the IOC resultant direction. We describe this phenomenon as coherence capture. Coherence capture was found to be effective between plaids with 0.5, 1.0, and 1.5 c/deg components and gratings of 3.0, 6.0 and 9.0 c/deg respectively. It was also found to be effective between plaids with 3.0 c/deg components and gratings of 0.5 c/deg. However, coherence capture between higher spatial frequency plaids and lower spatial frequency gratings became less effective when the component spatial frequencies of the plaid increased.

Humans

Spatial frequency mechanisms with short-wavelength-sensitive cone inputs.

We have estimated the minimum number and frequency tuning of spatial mechanisms with Short-Wavelength-Sensitive (SWS)-cone inputs. This was accomplished by isolating SWS cones with intense, long-wavelength (yellow) adaptation, and measuring threshold elevation functions for short-wavelength, spatially localized test stimuli masked by obliquely oriented, short-wavelength, cosine gratings. Peak spatial frequency of the cosine gratings and test stimuli varied from 0.25 to 2.83 cpd in 0.5 octave steps. Results derived in this manner demonstrate that SWS cones input to at least two orientation selective mechanisms with peak spatial frequencies of approx. 0.7 and 1.4 cpd, respectively. The frequency tuning of the isolated-SWS-cone, spatial frequency mechanisms resemble closely the lowest two mechanisms measured with luminance modulation (i.e. normal viewing conditions where all cones contribute to the response).

Contrast Sensitivity

A psychophysically motivated model for two-dimensional motion perception.

A quantitative model is developed to predict the perceived direction of moving two-dimensional patterns. The model incorporates both a simple motion energy pathway and a "texture boundary motion" pathway that incorporates response squaring before the extraction of motion energy. These pathways correspond to Fourier and non-Fourier motion pathways and are hypothesized to reflect processing in the V1-MT and V1-V2-MT pathway, respectively. A cosine-weighted sum of these pathways followed by competitive feedback inhibition accurately predicts the perceived direction for patterns composed of two cosine gratings at different orientations ("plaids"). The model also predicts direction discrimination, differences between foveal and peripheral viewing, changes in perceived direction with exposure duration, motion masking, and motion transparency.

Computer Simulation

Diffraction studies of the particles of two closteroviruses: heracleum latent virus and heracleum virus 6.

X-ray diffraction from oriented specimens of purified preparations of particles of heracleum latent closterovirus (HLV) showed that they have a helical arrangement of protein subunits, and that the structure repeats in five helical turns in which there are 5q +/- 1 protein subunits, where q is an integer. The pitch of the helix was estimated to be 3.26 (+/- 0.10) nm. Optical diffraction patterns from electron micrographs of HLV particles give an estimated pitch of 3.3 (+/- 0.2) nm and show that the number of subunits in the repeat period is 5q-1, where q has a value of 8 or 9. Optical diffraction from electron micrographs of particles of a second closterovirus, heracleum virus 6, shows that they too have a helical structure which repeats in five turns, in which there are 5q +/- 1 protein subunits. The estimated pitch of the primary helix is 3.6 (+/- 0.2) nm, and the estimate of q is 9.

Microscopy, Electron

Translational control of pyrC expression mediated by nucleotide-sensitive selection of transcriptional start sites in Escherichia coli.

Expression of the pyrC gene, which encodes the pyrimidine biosynthetic enzyme dihydroorotase, is negatively regulated by pyrimidine availability in Escherichia coli. To define the mechanism of this regulation, an essential regulatory region between the pyrC promoter and the initial codons of the pyrC structural gene was identified. Mutational analysis of this regulatory region showed that the formation of a hairpin at the 5' end of the pyrC transcript, which overlaps the pyrC ribosome binding site, is required for repression of pyrC expression. Formation of the hairpin appears to be controlled by nucleotide-sensitive selection of the site of pyrC transcriptional initiation. When the CTP level is high, the major pyrC transcript is initiated with this nucleotide at a position seven bases downstream of the pyrC -10 region. This transcript is capable of forming a stable hairpin at its 5' end. When the CTP level is low and the GTP level is high, conditions found in cells limited for pyrimidines, the major pyrC transcript is initiated with GTP at a position two bases further downstream. This shorter transcript appears to be unable to form a stable hairpin at its 5' end. These results suggest a model for regulation in which the longer pyrC transcripts are synthesized predominantly under conditions of pyrimidine excess and form the regulatory hairpin, which blocks pyrC translational initiation. In contrast, the shorter pyrC transcripts are synthesized primarily under conditions of pyrimidine limitation, and they are readily translated, resulting in a high level of dihydroorotase synthesis. The data also indicate that a low level of pyrimidine-mediated regulation may occur at the level of transcriptional initiation.

Base Sequence

Curvature and separation discrimination at texture boundaries.

Visual discrimination of contour curvature was investigated by using contours defined by the locus of points at which the phase of a square-wave grating was shifted by 180 degrees (a texture boundary). Curvature-increment thresholds were measured for contour curvatures from 0.31 to 10.65 deg-1, for grating spatial frequencies of 4.0 and 16.0 cycles per degree (cpd), and for gratings in either sine or cosine phase at the point of maximum curvature. Thresholds for these conditions were compared with curvature discrimination at black-white edges. Grating phase had no effect on performance at any curvature or grating frequency, but 16.0-cpd gratings produced a threshold elevation at all curvatures by an average factor of 2.4. Two-line separation discrimination was also measured for lines defined by texture boundaries. These data can be predicted by a model incorporating end-stopped complex cells of a type reported physiologically in primate area V2.

Form Perception

The effects of dietary protein level on the reproductive performance of bobwhite hens.

Two experiments were conducted to evaluate the protein requirement of adult bobwhite quail. Flight-type quail were used in one experiment and meat-type quail in the other. Corn and soybean meal diets containing 12, 15, 18, 21, and 24% protein were fed. Increasing the protein level of the diet from 12 to 15% significantly increased egg production with the flight-type bird. However, only a nonsignificant increase in egg production was obtained with the meat-type birds when the protein level was increased to 15%. Higher levels of protein did not result in further increases in egg production in either strain. Increasing the protein from 12 to 18% (flight) or 21% (meat) resulted in increased egg weight. Egg mass of flight-type hens receiving 18 and 21% protein was significantly greater than egg mass from hens receiving 12 and 15% protein. Hatch of fertile eggs, hatch of total eggs, chick weight, or weight of adult birds were not affected by protein level. Feeding the 12% protein diet resulted in significantly reduced fertility in the flight-type birds but not in the meat-type birds.

Animal Feed

On the coexistence of stereopsis and binocular rivalry.

Dichoptically viewed complex texture stereograms with correlated spatial frequency information can yield stable depth perception, implying cooperative interaction between the two eyes. Dichoptically viewed dissimilar texture pairs may yield competition in the form of binocular rivalry. To study whether stereopsis and rivalry can spatially coexist when stimulus conditions for both are present, we had observers dichoptically view spatial frequency filtered random-dot patterns. The left eye viewed one half-image of an RDS; the right eye viewed the superimposition of the other RDS half-image (which when paired alone with the left-eye RDS yielded stereoscopic depth) and a noise target (which on its own engaged in rivalry with the right eye target). Observers judged the quality of depth and the rate of rivalry for these stereo-pairs. When the contrast of the noise component was low, observers experienced stereopsis and stable single vision that included the noise. At intermediate noise contrasts, local regions were seen either in rivalry or in stereoscopic depth, but rivalry and depth were not experienced at the same spatial location simultaneously. At high noise contrasts, the right eye target dominated almost exclusively, with little hint of stereopsis. Essentially the same pattern of results was obtained in forced-choice experiments in which observers judged the direction of stereoscopic tilt from vertical cosine gratings differing slightly in spatial frequency. Considered together, these results are inconsistent with theories positing that rivalry and stereopsis coexist at the same spatial location because they occur within independent, parallel pathways.

Depth Perception

Perceived speed of moving two-dimensional patterns.

When two cosine gratings drifting in different directions are superimposed they can form a coherently moving two-dimensional pattern (plaid) whose resultant speed is related to the component velocities by a geometric construction known as the intersection-of-constraints (IOC). When measured against a standard which has the same spatial frequency as its components, a plaid always appears to move slower than the IOC prediction. However, the perceived speed is generally faster than would be predicted if speed were judged based on the temporal frequency of either the components or the nodes of the plaid. On the other hand, when the standard has the same spatial period as the nodes, the plaid appears to move at the same rate as the predicted IOC resultant. Furthermore, a grating with the same spatial period as the nodes appears to move slower than a grating at the component spatial frequency, just the plaid does. It is therefore likely that speed is encoded similarly for both gratings and plaids, and that the perceived speed of both is determined by the spatial periodicity of the pattern. We have previously classified 2D moving patterns as either type I (resultant lies between component directions) or type II (resultant outside of components). We find that the perceived speed of both types can be accounted for on the basis of the nodal spatial period. Finally we present a model for velocity coding which is based on the responses of spatio-temporal mechanisms.

Contrast Sensitivity

Model of peripheral and amblyopic hyperacuity.

Vernier thresholds rise much more rapidly in the periphery than do grating thresholds. A similar dissociation between acuity and hyperacuity has been shown to be present in strabismic but not in anisometropic amblyopia, thus leading to the suggestion that the strabismic fovea is similar to the normal periphery. Here it is shown that a quantitative model for spatial pattern discrimination, which accounts for foveal hyperacuity data, can be extended to encompass both the periphery and amblyopia if appropriate alterations are made. For the periphery it is necessary to increase the size of model receptive fields and to introduce both spatial undersampling and position irregularity (i.e. irregularity in the location of cortical filters). The strabismic fovea also requires spatial undersampling and position irregularity but no change in receptive field size. Defects in the good eye of strabismics can be explained by spatial irregularity. Finally, the anisometropic fovea requires a reduction in mechanism sensitivity but neither spatial undersampling nor position irregularity.

Amblyopia

Neural models of stereoscopic vision.

Human stereopsis remains an enigma: how does the brain match features between the left and right eye images and compute disparity between these matched features? Developments in computational neuroscience and machine vision have led to several models of human stereopsis that provide insight into possible mechanisms underlying this phenomenon. These models, reviewed in this paper, adopt one of three general strategies. One class of models employs cooperative interactions, whereby a unique solution to the matching problem emerges from excitatory and inhibitory interactions among binocular neural elements. A second class of models implements matching and disparity computation serially over multiple spatial scales. A third class relies on local, non-interacting computations performed in parallel to overcome speed limitations inherent in the other models. Considered together, these theoretical developments offer fresh insights concerning the actual neural concomitants of binocular stereopsis.

Animals

Secondary structures of narcissus mosaic virus coat protein.

Circular dichroism (CD) measurements on the coat protein of narcissus mosaic virus particles show that the dominant secondary structure is the alpha-helix, with a 45 (+/- 2)% content. The beta-sheet content is much lower at 5 (+/- 3)%. Both values are essentially the same as those found in potato virus X coat protein. The CD results are used to assess the results of secondary structure prediction methods.

Capsid

Coarse spatial scales constrain the range of binocular fusion on fine scales.

To examine interactions among spatial scales in disparity processing, we have measured the upper disparity limit for binocular single vision (the diplopia threshold) for high-spatial-frequency test stimuli in the presence of cosine gratings of lower spatial frequency that defined a surface in depth. When the frequency of this grating surface was 2.0 octaves below that of the test, the test fusion range was reduced by a factor of 3-4 relative to the condition in which no grating surface was present. However, gratings 4.0 octaves below the test frequency had no effect, and the test and grating were seen transparently at different depths. Further experiments indicate that the effect is orientation specific and that high-frequency gratings do not affect low-frequency tests. Finally, experiments using grating surfaces tilted in depth indicate that fusion at high spatial frequencies is constrained to a range centered on the local disparity of the surface defined by the lower frequency. These results are important for computational models for stereopsis that are based on coarse-to-fine matching strategies.

Depth Perception

Response of broiler breeder females to feed restriction below recommended levels. 1. Growth and reproductive performance.

Arbor Acre broiler breeders were used to determine the effects on growth and reproductive performance of quantitative feed restriction below breeder recommended levels. Feed treatments were: 8% above standard (+8%); standard feeding program (STD); and 8 (-8%), 16 (-16%), and 24% (-24%) below standard. Proportional decreases in feed allocation resulted in corresponding decreases in body weight, frequency of double-yolked eggs, and number of days in production. Egg weight, fertility, hatchability, and female mortality to 64 wk of age were not significantly (P greater than or equal to .05) affected by the reduction in feed intake. Shell quality was significantly improved with the -16 and -24% feed treatments. A delay in sexual maturity caused a significant (P less than or equal to .05) decrease in average rate of lay (%hen-day) but not in total settable eggs for treatments -16 and -24% to 64 wk of age.

Animals

Measurements of genetic variation in residual metabolizable energy intake of laying hens.

An experiment was conducted to determine heritability of the residual component of feed consumption. The effect of test period length was also examined to determine the shortest test period that would result in reliable data. Three hundred and thirty-five pedigreed White Leghorn hens were used. The experiment began when the hens were 26 wk of age and lasted for 28 wk. The residual component of energy intake was determined for each hen for time periods of 2, 4, and 8 wk in length. These values were used to determine heritability. Analyses of the data for each period were performed in two steps. A reduced model, without pedigree information, was used to develop a regression model. A complete model was used for analyses of data. The procedure of starting egg mass output measurements 2 days after body weight measurements was more effective than starting records on the same days that body weights were obtained. The partial regression coefficients of ME intake decreased with age. Also the partial regression coefficients of ME on body weight change increased with the length of the test period. The partial regression coefficients of ME on egg mass increased slightly with age. Heritability of ME intake adjusted for metabolic body weight, body weight change, and egg mass output was highest (.567 +/- .186) when the test was calculated by 8-wk periods. However, the range of estimates over time was lowest when made for 4-wk periods.

Animals

Comparison of energy utilization efficiency among six lines of White Leghorns.

Individual records were used of feed consumption, BW, BW change, and egg mass (EM) output during a 4-wk period for 180 hens from six different lines of White Leghorn chickens (30 hens per line). The diet contained 16.45% protein and 2,825 kcal ME/kg. Feed consumption was used to calculate actual ME intake (AcME) for each hen. Multiple regression of AcME was performed with metabolic BW, BW change, and EM production as independent variables. The regression coefficients and the independent variables were then used to calculate the expected ME intake (ExME). The following values were calculated for each hen and were used to compare energy efficiency among the six lines: the residual component of energy intake (RES), defined as the difference between the AcME intake and ExME intake; the relative efficiency ratio (RER), defined as (ExME divided by AcME) X 100 (calculated using the partial regression coefficients of the overall equation); and feed conversion, the ratio of feed consumed to EM. Significant differences among the lines in efficiency of EM produced were observed regardless of the efficiency measurement used. Feed consumption did not indicate differences in RES or RER. A multiple regression equation was derived for each line. Significant differences were found among the six lines in their energy requirements for maintenance and for egg production. These results suggest the possible use of the partial regression coefficients as selection criteria for separately improving maintenance efficiency and egg production efficiency.

Analysis of Variance