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Homeotic genes have specific functional roles in the establishment of the Drosophila embryonic peripheral nervous system.

The Drosophila embryonic peripheral nervous system (PNS) contains segment-specific spatial patterns of sensory organs which derive from the ectoderm. Many studies have established that the homeotic genes of Drosophila control segment specific characteristics of the epidermis, and more recently these genes have also been shown to control gut morphogenesis through their expression in the visceral mesoderm (Tremml, G. and Bienz, M. (1989), EMBO J. 8, 2677-2685). We report here the roles of homeotic genes in establishing the spatial patterns of sensory organs in the embryonic PNS. The PNS was examined in embryos homozygous for mutations in the homeotic genes Sex combs reduced (Scr), Antennapedia (Antp), Ultrabithorax (Ubx), abdominal-A (abd-A) and Abdominal-B (Abd-B) with antibodies that label specific subsets of sensory organs. Our results suggest that the homeotic genes have specific roles in establishing the correct spatial patterns of sensory organs in their normal domains of expression. In addition, we also report the effects of ectopic expression of the homeotic genes labial (lab), Deformed (Dfd), Scr, Antp or Ubx on the normal development of sensory organs in the embryonic PNS. Interestingly, while previous studies have concluded that ectopic expression of the homeotic genes Dfd, Scr and Antp has no effect on the segmental identity of the abdominal segments, our results demonstrate that this is not true. We show that ectopic expression of these genes does result in the disruption of the developing PNS in the abdomen. Our results are suggestive of a role for the homeotic gene products in regulating genes which are necessary for generating sensory progenitor cells in the developing PNS.

Animals

Configural effects constrain Fourier models of pattern discrimination.

Many models of spatial pattern discrimination assume that judgments are based on information directly available from mechanisms tuned to limited ranges of spatial frequency and orientation. We tested the validity of this assumption for spatial frequency, orientation, and contrast information in a series of complex pattern discrimination experiments. Observers discriminated between simple gratings, between gratings masked by components that differed widely in spatial frequency and/or orientation, and between patterns that presented two cues to discrimination, one in each frequency and/or orientation band. Component cues were combined either in rigid-object correspondence (e.g. both components were rotated clockwise in one pattern and counterclockwise in the other) or in opposition (e.g. in one pattern one component was rotated clockwise, the other counterclockwise; the direction of rotation was reversed for each component in the second pattern). The results demonstrate that information from tuned pathways is not always used directly in making spatial judgments, but in some cases is combined across wide regions of the Fourier domain prior to the discrimination decision. We find two distinct patterns of combination that appear to independently signal information about texture and edges. These findings provide a potential link between low-level, spatially tuned analyzers in the visual system and higher-level pattern processing mechanisms.

Adult

Genetic population structure of Italy. I. Geographic patterns of gene frequencies.

The diversity of spatial patterns of 61 allele frequencies for 20 genetic systems (15 loci) in Italy is presented. Blood antigens, enzymes, and proteins were analyzed. The total number of data points over all systems and localities was 1119. We used homogeneity tests, one-dimensional and directional spatial correlograms, and SYMAP interpolated surfaces. The data matrices were reduced by clustering techniques to reveal the principal patterns. Only a few allele frequency surfaces are strongly correlated across loci. All systems but one (ADA) exhibit significant heterogeneity in allele frequencies among the localities. Significant spatial patterns are shown by 27 of the 61 surfaces. Only one pattern (cde; system 4.19) is clinal; another (PGM1) exhibits a pure isolation by distance pattern; the others show long-range differentiation in addition to the short-distance decline of autocorrelation expected under isolation by distance. There is a marked decline in overall genetic similarity with distance for most variables. The 27 spatially significant alleles in Italy are also significantly patterned in Europe, but in all but 2 cases the country-wide and continent-wide patterns differ. The Italian patterns are due to forces specific to Italy. Differential selection for alleles associated with malaria is still evident. Whereas short-range differentiation can with malaria is still evident. Whereas short-range differentiation can be explained by isolation by distance, long-range differentiation appears to be due to demographic changes in certain populations that may be maintained by physical and linguistic isolation.

Gene Frequency

Spectral Transforms as a Tool to Optimize Digital Phenotyping in Biological Images.

Modern livestock breeding has mastered genotyping. Genome-wide association studies, genomic selection, and SNP arrays enable genetic merit prediction at lower cost. However, phenotyping remains the bottleneck, as manual measurement is slow, expensive, subjective, and unable to capture spatial or temporal trait organization. Digital phenotyping via artificial intelligence could resolve this, but deep learning requires thousands of labelled examples, impractical when phenotyping cost itself limits datasets to hundreds of individuals. This creates a paradox: AI could accelerate phenotyping but requires large numbers of samples to train the models. Here, we demonstrate that integrating computer vision with machine learning offers sample-efficient digital phenotyping using eggshell colour as a model system. Rather than learning features from scratch (deep learning), we engineer physically motivated features via Wavelet transforms that decompose images into multi-scale spatial components. Wavelet features captured 14.2 percentage points more variance (R2&#x2009;=&#x2009;0.976 vs. 0.834, p&#x2009;<&#x2009;0.001) than standard colorimetry, with 50% better sample efficiency (achieving at n&#x2009;=&#x2009;60 what colorimetry required n&#x2009;=&#x2009;120). Variance decomposition revealed 77% of discriminative capacity derives from spatial patterns (bands, spots, gradients) invisible to scalar averages. Additionally, we identified "cryptic phenotypes" (3.3%) where spatial patterns contradicted average colour, cases where colorimeters failed but Wavelets succeeded. The underlying principle-that spatial decomposition can recover organizational information lost by scalar averaging-may be applicable to other traits with spatial or temporal structure, such as marbling, dermatitis, or pigmentation rhythms, although whether comparable performance gains would be observed remains to be tested empirically. Hence, for breeding programs implementing genomic selection, computer vision-based digital phenotyping captures complex trait variation without massive training datasets, addressing the bottleneck that increasingly limits genetic progress as genotyping becomes trivial.

Wavelet transform

Reading twisted text: implications for the role of saccades.

These experiments investigated how the quality of saccadic skill limits the acquisition of visual information during a reading task. Subjects read text in which the spatial pattern of saccades was varied by reversing the order of words in a line, the order of letters in a word, or both. Some of these transformations drastically altered the customary visual appearance of words. To distinguish visual from oculomotor influences on reading, letters, in some conditions, were rotated 180 deg to produce text in which the customary visual appearance of words was destroyed while the order of words and letters remained unchanged. We found that the directional pattern of saccades had relatively modest effects on reading speed under the instruction to read accurately. The size of saccades had large effects on reading speed. Text in which familiar patterns of letters were destroyed, either by changing letter-order or letter-orientation, was read by sequences of small (less than 30') saccades made to look at every letter, or every alternate letter. Separate tests of letter recognition showed that these small saccades were necessary because recognition of letters drops sharply as a function of eccentricity in the absence of familiar letter patterns. Frequent small saccades slowed reading in that durations of the pauses before saccades increased when saccade size fell below 30-60'. We found a similar pattern of increased saccadic latency with decreasing saccade size when subjects used saccades to track a point whose motion mimicked their own reading eye movement patterns. The long latencies before small saccades in the point-tracking task showed that saccadic programming difficulties contributed to the long pause durations before small saccades during reading. The observed difficulty in programming small saccades means that valid inferences about the duration of visual or cognitive processes cannot be drawn from the temporal pattern of saccades unless the relative difficulty and time required to program different spatial patterns of saccades is taken into account.

Eye Movements

Spatial harmonics and pattern specification in early Drosophila development. Part I. Bifurcation sequences and gene expression.

Molecular probes have now provided an unprecedented wealth of detail revealing the changing spatial patterns of gene products in early Drosophila development. This is examined for dynamic properties which might provide insights into the underlying behaviour of the patterning process. What emerges is that transcripts and protein products of members of the major categories of zygotically active genes involved in segmentation pass through transient spatial patterns that are suggestive of harmonic sequences arising from spatial frequency-doubling bifurcations. That is to say, these patterns are typically periodic in space and show a doubling in the number of domains of spatial expression as development proceeds. One of these patterns reflects the primary functional role of the gene in the establishment of the spatial pattern. The different categories of segmentation gene pass through these transients at different rates, those with the longest functional wavelength progressing most slowly. Each gene in a category has its own unique phase relationship to other members, as well as particular variations on the harmonic sequence theme. The result is that the developing embryo experiences a spatial hierarchy of phase-shifted patterning influences that span the range from the whole embryo to single segments, providing progressively more spatial resolution in the patterning process. The characteristic transients and the dynamic relationships between genes of the different categories suggest that gene products expressed in longer-wavelength patterns act as bifurcation parameters on the dynamic system generating the next shorter wavelength category. Such parametric influences are known to result in frequency-doubling bifurcations in Turing reaction-diffusion systems. A general model is proposed of a hierarchically-nested set of quasi-autonomous dynamic systems involving gene activities that can generate the progressively finer spatial order that emerges during embryogenesis. This model has implications for the general stability properties of evolving epigenetic systems.

Animals

Discrete analysis of spatial-sensitivity models.

The visual representation of spatial patterns begins with a series of linear transformations: the stimulus is blurred by the optics, spatially sampled by the photoreceptor array, spatially pooled by the ganglion-cell receptive fields, and so forth. Models of human spatial-pattern vision commonly summarize the initial transformations by a single linear transformation that maps the stimulus into an array of sensor responses. Some components of the initial linear transformations (e.g., lens blurring, photoreceptor sampling) have been estimated empirically; others have not. A computable model must include some assumptions concerning the unknown components of the initial linear encoding. Even a modest sketch of the initial visual encoding requires the specification of a large number of sensors, making the calculations required for performance predictions quite large. We describe procedures for reducing the computational burden of current models of spatial vision that ensure that the simplifications are consistent with the predictions of the complete model. We also describe a method for using pattern-sensitivity measurements to estimate the initial linear transformation. The method is based on the assumption that detection performance is monotonic with the vector length of the sensor responses. We show how contrast-threshold data can be used to estimate the linear transformation needed to characterize threshold performance.

Humans

Perimetry of contrast detection thresholds of moving spatial sine patterns. II. The far peripheral visual field (eccentricity 0 degrees-50 degrees).

Contrast detection thresholds for moving sine wave gratings were obtained at the fovea and at eccentricities of 6 degrees, 12 degrees, 21 degrees, 32 degrees, and 50 degrees on the nasal horizontal meridian. The field subtended 4 degrees X 4 degrees. Spatial frequencies ranged from 0.25 cpd up to the resolution limit, temporal frequencies from 0.1 Hz up to the CFF. Mean retinal illuminance was 10 trolands. We find for these conditions: (i) For any eccentricity there exists a unique combination of spatial frequency and velocity for which the threshold is a minimum. (Extremes are 2 cpd and 2 degrees s-1 at the fovea, and 0.5 cpd and 12 degrees s-1 at an eccentricity of 50 degrees. (ii) Acuity depends little on velocity, the CFF only little on spatial frequency. (iii) The higher the eccentricity, the higher the threshold for any drifting sine wave pattern. Except for this the qualitative threshold behavior as a function of spatial and temporal frequency is identical at the fovea and at eccentricities up to 50 degrees. The thresholds double every 12 degrees for spatial frequencies of 0.25-2 cpd. For a given spatial frequency the visual field is blind beyond a certain critical eccentricity. This critical eccentricity is a monotonically decreasing function of spatial frequency.

Adult

The dynamics of infection of Tribolium confusum by Hymenolepis diminuta: the influence of infective-stage density and spatial distribution.

The mean parasite burden of a population of Tribolium confusum is shown to rise to a plateau as the exposure density of infective eggs of Hymenolepis diminuta increases. The level of this plateau is shown to be dependent on the nutritional status of the host population, being depressed from approximately 18 cysticeroids/beetle in hosts which have been starved prior to experimentation, to approximately 2 cysticercoids/beetle in satiated hosts. A simple model is used to describe the shape of this infection functional response in terms of the predator-prey interaction between hosts (T. confusum) and parasite infective stages (H. diminuta eggs). The distribution of successful infections/host is shown to be over-dispersed, even when hosts are exposed to infective stages arranged in a uniform spatial pattern. The over-dispersion of parasite numbers/host is shown to become more severe as the spatial pattern of infective stages changes from under-dispersed, through random, to over-dispersed. Experimental results are discussed in relation to the dynamics of parasite-host interactions, in which infection takes place by host ingestion of a free-living infective stage.

Feeding Behavior

Sulforhodamine labeling of neural circuits engaged in motor pattern generation in the in vitro turtle brainstem-cerebellum.

A fluorescent molecular probe was used in combination with a novel in vitro preparation to study spatial patterns of neural activity associated with motor pattern generation. The in vitro brainstem-cerebellum preparation takes advantage of the turtle's unusual resistance to anoxia to preserve the entire neural network that connects the cerebellum, red nucleus, and reticular formation. This preparation was bathed in a 0.01% solution of sulforhodamine while it was activated unilaterally by electrical stimulation of the dorsal quadrant of the spinal cord for 1 hr. Sulforhodamine is a small, sulfonated, highly charged fluorescent molecule that is taken up by endocytosis. To examine its distribution in the cerebellum and brainstem, coronal sections were prepared and viewed under epifluorescence illumination. Distinctive spatial patterns of labeling were associated with unilateral electrical stimulation of the in vitro network, suggesting that dye uptake was activity dependent. Blockade of uptake with altered magnesium and calcium concentrations indicated that single spike discharge evoked ortho- or antidromically was insufficient to induce dye uptake. Instead, sulforhodamine staining correlated with the presence of burst discharge that was recorded extracellularly from the red nucleus. Blockade of burst discharge with excitatory amino acid receptor antagonists prevented dye uptake in the red nucleus, the lateral cerebellar nucleus, and other structures that are known to be interconnected by recurrent anatomical pathways. These results suggest that sulforhodamine is internalized by intensely active neurons. The spatial distributions of label support the hypothesis that burst discharges in the turtle red nucleus are mediated by excitatory amino acid neurotransmitters and sustained by recurrent excitation in cerebellorubral synaptic pathways. Positive feedback in these recurrent pathways may provide an important driving force for the generation of motor programs that control limb movements.

Animals

A model of neural network for spatiotemporal pattern recognition.

A model of neural network to recognize spatiotemporal patterns is presented. The network consists of two kinds of neural cells: P-cells and B-cells. A P-cell generates an impulse responding to more than one impulse and embodies two special functions: short term storage (STS) and heterosynaptic facilitation (HSF). A B-cell generates several impulses with high frequency as soon as it receives an impulse. In recognizing process, an impulse generated by a P-cell represents a recognition of stimulus pattern, and triggers the generation of impulses of a B-cell. Inhibitory impulses with high frequency generated by a B-cell reset the activities of all P-cells in the network. Two examples of spatiotemporal pattern recognition are presented. They are achieved by giving different values to the parameters of the network. In one example, the network recognizes both directional and non-directional patterns. The selectivities to directional and non-directional patterns are realized by only adjusting excitatory synaptic weights of P-cells. In the other example, the network recognizes time series of spatial patterns, where the lengths of the series are not necessarily the same and the transitional speeds of spatial patterns are not always the same. In both examples, the HSF signal controls the total activity of the network, which contributes to exact recognition and error recovery. In the latter example, it plays a role to trigger and execute the recognizing process. Finally, we discuss the correspondence between the model and physiological findings.

Brain

Expression of the murine homeo box gene Hox 1.5 during embryogenesis.

The spatial pattern of expression of the murine homeo box-containing gene Hox 1.5 was studied during embryogenesis. In situ hybridization of single-stranded RNA probes to mouse embryo sections revealed a specific spatial distribution of the Hox 1.5 transcripts in mouse embryos 8.5 to 12.5 days postcoitum (p.c.). Analysis of mouse embryos 8.5 days p.c. showed that the gene is expressed in a spatially restricted manner. Expression appears to be limited to the central nervous system with an anterior boundary in the hindbrain and extending posteriorly through caudal regions of the spinal cord. The same spatial pattern of expression was observed in embryos 9.5 to 12.5 days p.c. These results show that the murine Hox 1.5 gene is expressed in a spatially restricted manner during embryonic development similar to the patterns observed in Drosophila homeotic genes.

Animals

On pattern formation mechanisms for lepidopteran wing patterns and mammalian coat markings.

The patterns on wings of Lepidoptera can be generated with a few pattern elements, but no mechanism has been suggested for producing them. I consider two of the basic patterns, namely, central symmetry and dependent patterns. A biochemically plausible model mechanism is proposed for generating major aspects of these patterns, based on a diffusing morphogen that activates a gene or colour-specific enzyme in a threshold manner to generate a stable heterogeneous spatial pattern. The model is applied to the determination stream hypothesis of Kühn & von Engelhardt (Wilhelm Roux Arch. Entw Mech. Org. 130, 660 (1933)), and results from the model compared with their microcautery experiments on the pupal wing of Ephestia kühniella. In the case of dependent patterns, results are compared with patterns on specific Papilionidae. For the same mechanism and a fixed set of parameters I demonstrate the important roles of geometry and scale on the spatial patterns obtained. The results and evidence presented here suggest the existence of diffusion fields of the order of several millimetres, which are very much larger than most embryonic fields. The existence of zones of polarizing activity is also indicated. Colour patterns on animals are considered to be genetically determined, but the mechanism is not known. I have previously suggested that a single mechanism that can exhibit an infinite variety of patterns is a candidate for that mechanism, and proposed that a reaction-diffusion system that can be diffusively driven unstable could be responsible for the laying down of the spacing patterns that generates the pre-pattern for animal coat markings. For illustrative purposes I consider, a practical reaction mechanism, which exhibits substrate inhibition, and show that the geometry and scale of the domain (part of the epidermis) play a crucial role in the structural patterns that result. Patterns are obtained for a selection of geometries, and general features are related to the coat colour distribution in the spotted Felidae, giraffe, zebra and other animals. The patterns depend on the initial conditions, but for a given geometry and scale are qualitatively similar, a positive feature of the model and a necessary model attribute in view of the pattern individuality on animals of the same species.

Animals

The development of basic mechanisms of pattern vision: spatial frequency channels.

The mature visual system possesses mechanisms that analyze visual inputs into bands of spatial frequency. This analysis appears to be important to several visual capabilities. We have investigated the development of these spatial-frequency channels in young infants. Experiment 1 used a masking paradigm to test 6-week-olds, 12-week-olds, and adults. The detectability of sine wave gratings of different spatial frequencies was measured in the presence and the absence of a narrowband noise masker. The 12-week data showed that at least two spatial-frequency channels with adultlike specificity are present at 12 weeks. The 6-week data did not reveal the presence of narrowband spatial-frequency channels. Experiment 2 used a different paradigm to investigate the same issue. The detectability of gratings composed of two sine wave components was measured in 6-week-olds and adults. The results were entirely consistent with those of experiment 1. The 12-week and adult data indicated the presence of narrowband spatial-frequency channels. The 6-week data did not. The results of these experiments suggest that the manner in which pattern information is processed changes fundamentally between 6 and 12 weeks of age.

Adult

Genetic interactions underlying flower color patterns in Antirrhinum majus.

Diverse spatial patterns of flower color in Antirrhinum can be produced by a series of alleles of pallida, a gene encoding an enzyme required for pigment biosynthesis. The alleles arose by imprecise excision of a transposable element, Tam3, and we show that they carry a series of deletions involving progressive removal of sequences adjacent to the excision site. This has enabled us to define three cis-acting upstream regions, A, B, and C, which differentially affect the level of pallida expression in distinct areas of the flower. We show further that an unlinked locus, delila, regulates the spatial distribution of pallida transcript. Deletion of regions ABC at the pallida locus uncouples pallida from regulation by delila, whereas deletion of A or AB brings pallida under regulation by delila in a new area of the flower. These results suggest that diverse patterns of pallida expression reflect the different ways in which alleles interact with a prepattern of both common and spatially specific genetic signals in the flower.

Alleles

Effects of posterior parietal and frontal neocortical lesions in the squirrel monkey.

Brightness discrimination, three forms of a spatial pattern discrimination in which the essential cue and site of reinforcement were separated (SSP), delayed response, form discrimination, and three forms of a spatial pattern discrimination in which the essential cue and site of reinforcement were identical (ISP) were given, in the order mentioned, to two groups of squirrel monkeys with frontal lesions were impaired on delayed response, and those with parietal lesions were impaired on form and SSP discriminations. Neither group was impaired on brightness discrimination. The results confirm and extend previous findings by other investigators that the posterior parietal cortex of nonhuman primates is critically involved in visually guided spatial discriminations when the primary cue and the site of reinforcement are separated.

Animals

Optical mapping of the early development of the response pattern to vagal stimulation in embryonic chick brain stem.

1. In both intact and slice preparations of vagus-brain stem isolated from 3- to 8-day-old chick embryos, the spatial pattern of neural responses to vagal stimulation and its development were assessed by means of multiple-site optical recording of electrical activity, using a voltage-sensitive merocyanine-rhodanine dye (NK2761) and a 12 x 12-element photodiode array. 2. The first neural responses, viz. fast optical signals (related to the action potential), were recorded in the 4-day-old brain stem preparation, and slow optical signals (related to excitatory postsynaptic potentials) were detected from late 7- and 8-day-old brain stem preparations. 3. The evoked optical signals appeared to be concentrated longitudinally in the central region of the stimulated side of the intact brain stem preparation and in a limited dorsal area in the slice preparation. The signal size gradually increased and the response area expanded as development proceeded. 4. Based on the above results, we have constructed developmental maps of the spatial patterns of the fast and slow optical responses. In the maps, the positions of the peak-size regions of the fast and slow signals were assessed and we have found that there were differences in the location of these areas for the fast vs. the slow signals in the late 7- and 8-day-old embryonic brain stem preparations. 5. In the maps for the late 7- and 8-day-old embryonic brain stems, the fast signal response area seems to correspond to the dorsal motor nucleus of the vagus nerve and the slow response area to the nucleus tractus solitarii.

Action Potentials

A novel spatial transcription pattern associated with the segmentation gene, giant, of Drosophila.

The segmentation gene, giant, is located in 3A1 within a cloned chromosome region surrounding the zeste locus. Rearrangement breakpoints associated with giant mutations were localized on the genomic clone map, and nearby transcription units were identified. One transcription unit is active during early embryogenesis and its transcripts are spatially localized from blastoderm into extended germband stages, consistent with expected expression patterns predicted by the 'gap' phenotype of giant mutants. Germ line transformation experiments using a 10-kb DNA fragment containing this transcription unit gave complete rescue of the abdominal giant defect but only partial correction of the head defect. The effect of mutations in three other gap loci, Kr, kni and hb, were also analyzed.

Alleles