Visual discrimination of simple geometrical patterns: I. Measurements for multiple element stimuli

We describe a method for the measurement of visual discrimination between simple patterns. The target to be discriminated is embedded in a background consisting of multiple, randomly positioned but identical elements, and is distinguished by a single parameter such as magnification or relative rotation. The positions of the target and background elements are varied randomly between presentations and discrimination for different values of the target parameter is measured in terms of the time taken for detection of the target. Using this method, we have studied discrimination of rotation and of magnification for simple pattern elements such as lines, triangles and squares. The results for rotation discrimination are interpreted as evidence for the activity of two discrimination mechanisms, one sensitive to the orientation of the lines from which the pattern elements are constructed and the other to the orientation of the pattern element relative to the visual field.     

Spatial, colour and contrast response characteristics of mechanisms which mediate discrimination of pattern orientation and magnification

We have measured response times for the detection of a single target presented against a set of reference elements which are characterised by combinations of four different stimulus parameters; colour, contrast polarity, magnification and orientation. The aim of the experiments was to determine the response characteristics of visual mechanisms which mediate target detection through the discrimination of orientation and magnification. In the first experiments, we determined sensitivity to differences in colour and contrast polarity, and show that the mechanisms responsible for the discrimination of orientation and of magnification are both selective in their responses to colour and to contrast polarity. There are, nonetheless, residual interactions between patterns of different contrast polarities and between those of different colour, and in the latter case, weak interactions persist under equiluminance conditions. In a second set of experiments, we examined the interactions between orientation and magnification. We conclude that the responses of visual mechanisms which mediate target detection through discrimination of orientation are markedly dependent on stimulus magnification whereas those which mediate detection through discrimination of magnification are, in contrast, relatively insensitive to stimulus orientation.     

Simultaneous processing of spatial and chromatic components of patterned stimuli by the human visual system

We report measurements on discrimination of orientation and magnification made for elements differentiated in colour and/or luminance from their background. By performing measurements at a series of background luminances and for fixed luminance of the elements, we show that with colour contrast, discrimination for both spatial parameters is unimpaired when the background is at isoluminance with the elements. Under simple luminance contrast, however, these discriminations become poorer when the background luminance is within some +/- 5% of that of the elements, and are completely absent when the two values are the same. A deuteranomalous subject is unable to make the spatial discrimination around the isoluminance point for colour contrasts which are too small for him to distinguish, but for which subjects with normal colour vision maintain spatial discriminations at isoluminance. This observation establishes that the physiological mechanisms of normal colour vision, rather than stimulus artefacts, mediate the observed spatial discriminations. We conclude that the visual processing of colour and spatial parameters such as orientation and magnification are intrinsically related to each other.     

The plural interpretability of German linking elements

In this paper, we take a closer theoretical and empirical look at the linking elements in German N1+N2 compounds which are identical to the plural marker of N1 (such as -er with umlaut, as in Häus-er-meer ‘sea of houses’). Various perspectives on the actual extent of plural interpretability of these pluralic linking elements are expressed in the literature. We aim to clarify this question by empirically examining to what extent there may be a relationship between plural form and meaning which informs in which sorts of compounds pluralic linking elements appear. Specifically, we investigate whether pluralic linking elements occur especially frequently in compounds where a plural meaning of the first constituent is induced either externally (through plural inflection of the entire compound) or internally (through a relation between the constituents such that N2 forces N1 to be conceptually plural, as in the example above). The results of a corpus study using the DECOW16A corpus and a split-100 experiment show that in the internal but not external plural meaning conditions, a pluralic linking element is preferred over a non-pluralic one, though there is considerable inter-speaker variability, and limitations imposed by other constraints on linking element distribution also play a role. However, we show the overall tendency that German language users do use pluralic linking elements as cues to the plural interpretation of N1+N2 compounds. Our interpretation does not reference a specific morphological framework. Instead, we view our data as strengthening the general approach of probabilistic morphology.     

P element-mediated duplications of genomic regions in Drosophila melanogaster

Previously we have described highly unstable yellow mutations induced by chimeric elements that consist of genomic sequences originating from different regions of the X chromosome flanked by identical copies of an internally deleted 1.2 kb P element. To study further the origin and the mechanism of formation of chimeric mobile elements, we analyzed complex y-sc mutations, induced by inversions between P elements located in the neighboring yellow and scute loci. The breakpoints of the inversions are flanked by two P elements in head-to-head orientation on one side and by one P element on the other side. Such an arrangement of P elements leads to frequent duplication into the site between the two P element copies located in head-to-head orientation of the yellow sequences adjacent to the single P element. The duplicated yellow sequences either partly replace the sequence of one of the P elements or are inserted between the conserved head-to-head oriented P elements. In some cases two copies of the yellow sequence are duplicated between the P elements in inverted tail-to-tail orientation. The structure of the P elements at the place of duplication and of the P element- yellow junction suggests that the described duplications, which form chimeric mobile elements, are generated through the previously proposed synthesis-dependent strand annealing mechanism.     

On the neuronal basis of figure-ground discrimination by relative motion in the visual system of the fly

It has been concluded in the preceding papers (Egelhaaf, 1985a, b) that two functional classes of output elements of the visual ganglia might be involved in figure-ground discrimination by relative motion in the fly: The Horizontal Cells which respond best to the motion of large textured patterns and the FD-cells which are most sensitive to small moving objects. In this paper it is studied by computer simulations (1) in what way the input circuitry of the FD-cells might be organized and (2) the role the FD-cells play in figure-ground discrimination. The characteristic functional properties of the FD-cells can be explained by various alternative model networks. In all models the main input to the FD-cells is formed by two retinotopic arrays of small-field elementary movement detectors, responding to either front-to-back or back-to-front motion. According to their preferred direction of motion the FD-cells are excited by one of these movement detector classes and inhibited by the other. The synaptic transmission between the movement detectors and the FD-cells is assumed to be non-linear. It is a common property of all these model circuits that the inhibition of the FD-cells induced by large-field motion is mediated by pool cells which cover altogether the entire horizontal extent of the visual field of both eyes. These pool cells affect the response of the FD-cells either by pre- or postsynaptic shunting inhibition. Depending on the FD-cell under consideration, the pool cells are directionally selective for motion or sensitive to motion in either horizontal direction. The role the FD-cells and the Horizontal Cells are likely to play in figure-ground discrimination can be demonstrated by computer simulations of a composite neuronal model consisting of the model circuits for these cell types. According to their divergent spatial integration properties they perform different tasks in figure-ground discrimination: Whereas the Horizontal Cells mainly mediate information on wide-field motion, the FD-cells are selectively tuned to efficient detection of relatively small targets. Both cell classes together appear to be sufficient to account for figure-ground discrimination as it has been shown by analysis at the behavioural level.     

Multiple positive and negative elements involved in the regulation of expression of GSY1 in Saccharomyces cerevisiae

GSY1 is one of the two genes encoding glycogen synthase in Saccharomyces cerevisiae. Both the GSY1 message and the protein levels increased as cells approached stationary phase. A combination of deletion analysis and site-directed mutagenesis revealed a complex promoter containing multiple positive and negative regulatory elements. Expression of GSY1 was dependent upon the presence of a TATA box and two stress response elements (STREs). Expression was repressed by Mig1, which mediates responses to glucose, and Rox1, which mediates responses to oxygen. Characterization of the GSY1 promoter also revealed a novel negative element. This element, N1, can repress expression driven by either an STRE or a heterologous element, the UAS of CYC1. Repression by N1 is dependent on the number of these elements that are present, but is independent of their orientation. N1 repressed expression when placed either upstream or downstream of the UAS, although the latter position is more effective. Gel shift analysis detected a factor that appears to bind to the N1 element. The complexity of the GSY1 promoter, which includes two STREs and three distinct negative elements, was surprising. This complexity may allow GSY1 to respond to a wide range of environmental stresses.     

Synergy of features enables detection of texture defined figures

Traditional theories of early visual processing suggest that elementary visual features are handled in parallel by independent neural pathways. We studied the interaction of orientation and spatial frequency in the discrimination of Gabor random fields. Target textures differed from reference textures either in mean feature value, showing an edge-like transition between both textures (edge defined), or in the degree of feature homogeneity with smooth transitions (region defined). Irrespective of the kind of texture definition, we found strong cue summation for targets defined by both cues simultaneously, provided two conditions were fulfilled. First, they were barely discriminable when defined by one cue alone. Second, the target elements formed a closed 2D surface. Only marginal cue summation was observed when target elements were heterogeneously distributed in a predefined area, lacking a clear 2D shape. Our findings indicate that feature synergy enables figure-ground segregation when the information from independent feature-specific pathways is insufficient for solving this task.     

Four major sequence elements of simian virus 40 large T antigen coordinate its specific and nonspecific DNA binding.

By mutational analysis, we have identified a motif critical to the proper recognition and binding of simian virus 40 large tumor antigen (T antigen) to virus DNA sequences at the origin of DNA replication. This motif is tripartite and consists of two elements (termed A1 and B2) that are necessary for sequence-specific binding of the origin and a central element (B1) which is required for nonspecific DNA-binding activity. Certain amino acids in elements A1 (residues 152 to 155) and B2 (203 to 207) may make direct contact with the GAGGC pentanucleotide sequences in binding sites I and II on the DNA. Alternatively, these two elements could determine the proper structure of the DNA-binding domain, although for a number of reasons we favor the first possibility. In contrast, element B1 (183 to 187) is most likely important for recognizing a general structural feature of DNA. Elements A1 and B2 are nearly identical in all known papovavirus T antigens, whereas B1 is identical only in the closely related papovaviruses simian virus 40, BK virus, and JC virus. In addition to these three elements, a fourth (B3; residues 215 to 219) is necessary for the binding of T antigen to site II but not to site I. We propose that additional contact sites on T antigen are involved in the interaction with site II to initiate the replication of the viral DNA.     

Coordinate genetic control of yeast fatty acid synthase genes FAS1 and FAS2 by an upstream activation site common to genes involved in membrane lipid biosynthesis.

A systematic search for upstream controlling elements necessary for efficient expression of the yeast fatty acid synthase genes FAS1 and FAS2 revealed identical activation sites, UASFAS, in front of both FAS genes. The individual element confers, in a heterologous yeast test system, an approximately 40-fold stimulation of basal gene expression. The UASFAS motifs identified have the consensus sequence TYTTCACATGY and function in either orientation. The same sequence motif is found in the upstream regions of all so far characterized yeast genes encoding enzymes of phospholipid biosynthesis. In gel retardation assays, a protein factor, Fbf1 (FAS binding factor), was identified which interacted with UASFAS. The UASFAS motif proved to be an inositol/choline responsive element (ICRE) conferring strict repression by exogenous inositol and choline on a heterologous reporter gene. Its core sequence perfectly matches the CANNTG motif typical of basic helix-loop-helix DNA-binding proteins. In contrast to the individual UASFAS element, the intact yeast FAS promoters are not significantly influenced by inositol and choline, and thus allow nearly constitutive fatty acid synthase production. Available evidence suggests that additional cis- and trans-acting elements, other than UASFAS and Fbf1, are involved in this constitutive FAS gene expression.     

Multiple copies of a G-rich element upstream of a cAMP-inducible Dictyostelium gene are necessary but not sufficient for efficient gene expression.

The cysteine proteinase 1 (CP1) and cysteine proteinase 2 (CP2) genes of Dictyostelium discoideum encode co-ordinately expressed mRNA sequences which are inducible by extracellular cAMP. There are short, G-rich sequence elements upstream of both genes and we have previously shown that deletion of these elements from the CP2 gene abolishes cAMP-inducibility. We show here that the G-rich element from the CP1 gene is functionally homologous to that in the CP2 gene by reconstituting cAMP-inducibility in a deletion mutant of the CP2 gene using CP1-derived sequences. Both the CP1 and CP2 genes contain multiple G-rich elements. We show that efficient induction requires at least two copies of the CP1 element and that their relative orientation is unimportant. Two copies of an inverted relative orientation are, however, inactive when moved upstream of their normal position and are incapable of conferring cAMP-inducibility on a heterologous gene. These observations suggest that these sequences are either essential promoter elements, not themselves interacting with the inducer, or that their interaction with a separate class of control sequences is necessary for inducible expression.     

Characterization of two divergently transcribed Dictyostelium gene pairs and identification of G-rich sequence element lying between them with the characteristics of a basal promoter element

The cysteine proteinase 1 (CP1) and cysteine proteinase 2 (CP2) genes of Dictyostelium discoideum encode coordinately expressed mRNA sequences that are inducible by extracellular cAMP. Both genes form part of divergently transcribed gene pairs. The gene proximal to CP1 is coordinately regulated and encodes a protein containing several potential zinc binding domains of the kind found in DNA binding proteins. The gene proximal to CP2 is a constitutively transcribed gene of unknown function. There are multiple, short, G-rich sequence elements between both gene pairs, and deletion of the pair of elements 200 nucleotides upstream from the CP2 gene abolishes cAMP-inducibility. A synthetic oligonucleotide, containing two copies of the G-rich element from the CP1 gene, will reconstitute cAMP-inducibility in the deletion mutant of the CP2 gene. This shows that the elements in the two genes are functionally homologous. Efficient induction requires at least two copies of the CP1 element, but their relative orientation is unimportant. Two copies in an inverted orientation are, however, inactive when moved upstream of their normal position and are incapable of conferring cAMP-inducibility on a heterologous gene. These observations suggest that these sequences are either essential promoter elements, not themselves interacting with the inducer, or that their interaction with a separate class of control sequences is necessary for inducible expression.     

Nucleotide sequence characterization of Ty 1-17, a class II transposon from yeast

We have determined the nucleotide sequence of a class II yeast transposon (Ty 1-17) which is found just centromere-distal to the LEU2 structural gene on chromosome III of Saccharomyces cerevisiae. The complete element is 5961 bp long and is bounded by two identical, directly repeated, delta sequences of 332 bp each. The sequence organization indicates that Ty 1-17 is a retrotransposon, like the class I elements characterized previously. It contains two long open reading-frames, TyA (439 amino acids) and TyB (1349 amino acids). In this paper, the sequences of the two classes of yeast transposon are compared with one another and with analogous elements, such as retroviral proviruses, cauliflower mosaic virus and copia sequences. Features of the Ty 1-17 sequence which may be important to its mechanism of transposition and its genetic action are discussed.     

A new approach for assessment of mental architecture: repeated tagging

A new approach to the study of a relatively neglected property of mental architecture-whether and when the already-processed elements are separated from the to-be-processed elements-is proposed. The process of numerical proportion discrimination between two sets of elements defined either by color or by orientation can be described as sampling with or without replacement (characterized by binomial or hypergeometric probability distributions respectively) depending on the possibility to tag an element once or repeatedly. All empirical psychometric functions were approximated by a theoretical model showing that the ability to keep track of the already tagged elements is not an inflexible part of the mental architecture but rather an individually variable strategy which also depends on conspicuity of perceptual attributes. Strong evidence is provided that in a considerable number of trials, observers tagged the same element repeatedly which can only be done serially at two separate time moments.     

Splicing of a critical exon of human Survival Motor Neuron is regulated by a unique silencer element located in the last intron

Humans have two nearly identical copies of the Survival Motor Neuron (SMN) gene, SMN1 and SMN2. In spinal muscular atrophy (SMA), SMN2 is not able to compensate for the loss of SMN1 due to exclusion of exon 7. Here we describe a novel inhibitory element located immediately downstream of the 5' splice site in intron 7. We call this element intronic splicing silencer N1 (ISS-N1). Deletion of ISS-N1 promoted exon 7 inclusion in mRNAs derived from the SMN2 minigene. Underlining the dominant role of ISS-N1 in exon 7 skipping, abrogation of a number of positive cis elements was tolerated when ISS-N1 was deleted. Confirming the silencer function of ISS-N1, an antisense oligonucleotide against ISS-N1 restored exon 7 inclusion in mRNAs derived from the SMN2 minigene or from endogenous SMN2. Consistently, this oligonucleotide increased the levels of SMN protein in SMA patient-derived cells that carry only the SMN2 gene. Our findings underscore for the first time the profound impact of an evolutionarily nonconserved intronic element on SMN2 exon 7 splicing. Considering that oligonucleotides annealing to intronic sequences do not interfere with exon-junction complex formation or mRNA transport and translation, ISS-N1 provides a very specific and efficient therapeutic target for antisense oligonucleotide-mediated correction of SMN2 splicing in SMA.     

Formation of chromosomal tandem arrays of the SXT element and R391, two conjugative chromosomally integrating elements that share an attachment site

The SXT element, a conjugative, self-transmissible, integrating element (a constin) originally derived from a Vibrio cholerae O139 isolate from India, and IncJ element R391, originally derived from a South African Providencia rettgeri isolate, were found to be genetically and functionally related. Both of these constins integrate site specifically into the Escherichia coli chromosome at an identical attachment site within the 5' end of prfC. They encode nearly identical integrases, which are required for chromosomal integration, excision, and extrachromosomal circularization of these elements, and they have similar tra genes. Therefore, these closely related constins have virtually identical mechanisms for chromosomal integration and dissemination. The presence of either element in a recipient cell did not significantly reduce its ability to acquire the other element, indicating that R391 and SXT do not encode surface exclusion determinants. In cells harboring both elements, SXT and R391 were integrated in tandem fashion on the chromosome, and homologous recombination appeared to play little or no role in the formation of these arrays. Interference between R391 and SXT was detected by measuring the frequency of loss of an unselected resident element upon introduction of a second selected element. In these assays, R391 was found to have a stronger effect on SXT stability than vice versa. The level of expression and/or activity of the donor and recipient integrases may play a role in the interference between these two related constins.     

Comparative studies of the endonucleases from two related Xenopus laevis retrotransposons, Tx1L and Tx2L: target site specificity and evolutionary implications

In the genome of the South African frog, Xenopus laevis, there are two complex families of transposable elements, Tx1 and Tx2, that have identical overall structures, but distinct sequences. In each family there are approximately 1500 copies of an apparent DNA-based element (Tx1D and Tx2D). Roughly 10% of these elements in each family are interrupted by a non-LTR retrotransposon (Tx1L and Tx2L). Each retrotransposon is flanked by a 23-bp target duplication of a specific D element sequence. In earlier work, we showed that the endonuclease domain (Tx1L EN) located in the second open reading frame (ORF2) of Tx1L encodes a protein that makes a single-strand cut precisely at the expected site within its target sequence, supporting the idea that Tx1L is a site-specific retrotransposon. In this study, we express the endonuclease domain of Tx2L (Tx2L EN) and compare the target preferences of the two enzymes. Each endonuclease shows some preference for its cognate target, on the order of 5-fold over the non- cognate target. The observed discrimination is not sufficient, however, to explain the observation that no cross-occupancy is observed – that is, L elements of one family have never been found within D elements of the other family. Possible sources of additional specificity are discussed. We also compare two hypotheses regarding the genome duplication event that led to the contemporary pseudotetraploid character of Xenopus laevis in light of the Tx1L and Tx2L data. This revised version was published online in July 2006 with corrections to the Cover Date.     

Two distinct SECIS structures capable of directing selenocysteine incorporation in eukaryotes.

Translation of UGA as selenocysteine requires specific RNA secondary structures in the mRNAs of selenoproteins. These elements differ in sequence, structure, and location in the mRNA, that is, coding versus 3' untranslated region, in prokaryotes, eukaryotes, and archaea. Analyses of eukaryotic selenocysteine insertion sequence (SECIS) elements via computer folding programs, mutagenesis studies, and chemical and enzymatic probing has led to the derivation of a predicted consensus structural model for these elements. This model consists of a stem-loop or hairpin, with conserved nucleotides in the loop and in a non-Watson-Crick motif at the base of the stem. However, the sequences of a number of SECIS elements predict that they would diverge from the consensus structure in the loop region. Using site-directed mutagenesis to introduce mutations predicted to either disrupt or restore structure, or to manipulate loop size or stem length, we show that eukaryotic SECIS elements fall into two distinct classes, termed forms 1 and 2. Form 2 elements have additional secondary structures not present in form 1 elements. By either insertion or deletion of the sequences and structures distinguishing the two classes of elements while maintaining appropriate loop size, conversion of a form 1 element to a functional form 2-like element and of a form 2 to a functional form 1-like element was achieved. These results suggest commonality of function of the two classes. The information obtained regarding the existence of two classes of SECIS elements and the tolerances for manipulations of stem length and loop size should facilitate designing RNA molecules for obtaining high-resolution structural information about these elements.