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PubMed1986

T-even type phages can change their host range by recombination with gene 34 (tail fibre) or gene 23 (head).

T-even type phages recognize their cellular receptors with the tip of their long tail fibres. The gene products involved in receptor recognition are proteins 37 and 38. While screening libraries of phage K3 with a probe of gene 38 from phage T2, a class of weakly hybridizing clones was found in addition to the expected clones of gene 38 of K3. One of these clones was identified as being from gene 23 of the phage which codes for the major head subunit; another clone originated from gene 34, which codes for the proximal half of the long tail fibres. Neither gene product 23 nor 34 is involved in receptor recognition. Phages can recombine with the DNA of the gene 23 and gene 34 clones and change the host range.

Base Sequence↗

PubMed1978

Promoter recognition by phage SP01-modified RNA polymerase.

A modified form of Bacillus subtilis RNA polymerase containing a phage SP01-coded regulatory protein (the gene 28 product) selectively transcribes "middle" genes of the phage genome in vitro. In this paper, we identify a subset of restriction endonuclease fragments of SP01 DNA that promote specific transcription by the phage-modified polymerase. In the absence of nucleoside triphosphates, RNA polymerase containing the gene 28 protein selectively binds to these DNA fragments thereby forming stable binary complexes that can be isolated on nitrocellulose filters. In contrast, unmodified RNA polymerase containing sigma factor selectively binds to and transcribes a subset of phage DNA fragments that contain "early" sequences and that are in large part distinct from the fragments recognized by the phage-modified transcriptase. Our results strongly suggest that phage "early" and "middle" genes are transcribed from distinct promoters and that the RNA polymerase containing the gene 28 protein binds to sites that are located at or near promoters for SP01 "middle" genes.

Bacillus subtilis↗

PubMed1990

Representational guidance of action production in observational learning: a causal analysis.

This experiment tested the hypothesis that the number of model presentations and verbal coding of modeled actions affect reproduction accuracy through their effect on cognitive representation. Subjects viewed a complex action pattern either two or eight times with or without verbal coding to highlight the dynamic structure of the component actions and their temporal sequencing. They then received, in order, a recognition test and a pictorial-arrangement test to assess the accuracy of their cognitive representations of the modeled actions. Subsequently, all subjects were tested for their ability to reproduce the action pattern from memory. Results showed that increased exposure to modeled actions enhanced the accuracy of both the cognitive representation and the behavioral reproduction. Verbal coding also increased cognitive and reproduction accuracy, but only when combined with multiple opportunities to observe the modeled actions. A causal analysis confirmed that the effects of multiple exposures and verbal coding were entirely mediated by changes produced in the accuracy of cognitive representation.

Journal Article↗

PubMed1986

Cognitive aspects of haptic form recognition by blind and sighted subjects.

Studies using haptic form recognition tasks have generally concluded that the adventitiously blind perform better than the congenitally blind, implicating the importance of early visual experience in improved spatial functioning. The hypothesis was tested that the adventitiously blind have retained some ability to encode successive information obtained haptically in terms of a global visual representation, while the congenitally blind use a coding system based on successive inputs. Eighteen blind (adventitiously and congenitally) and 18 sighted (blindfolded and performing with vision) subjects were tested on their recognition of raised line patterns when the standard was presented in segments: in immediate succession, or with unfilled intersegmental delays of 5, 10, or 15 seconds. The results did not support the above hypothesis. Three main findings were obtained: normally sighted subjects were both faster and more accurate than the other groups; all groups improved in accuracy of recognition as a function of length of interstimulus interval; sighted subjects tended to report using strategies with a strong verbal component while the blind tended to rely on imagery coding. These results are explained in terms of information-processing theory consistent with dual encoding systems in working memory.

Adolescent↗

PubMed1992

Cytotoxic T lymphocytes (CTL) against a transforming gene product select for transformed cells with point mutations within sequences encoding CTL recognition epitopes.

The 94-kD large tumor (T) antigen specified by simian virus 40 (SV40) is sufficient to induce cell transformation. T antigen contains four H-2Db-restricted cytotoxic T lymphocyte (CTL) recognition epitopes that are targets for CTL clones Y-1, Y-2, Y-3, and Y-5. These epitopes have been mapped to T antigen amino acids 207-215 (site I), 223-231 (sites II and III), and 489-497 (site V), respectively. Antigenic site loss variant cells that had lost one or more CTL recognition epitopes were previously selected by coculturing SV40-transformed H-2Db cells with the site-specific Db-restricted CTL clones. The genetic bases for T antigen CTL recognition epitope loss from the variant cells were identified by DNA amplification and direct sequencing of epitope-coding regions from variant cell DNAs. Cells selected for resistance to CTL clone Y-1 (K-1; K-1,4,5; K-3,1) carry deleted SV40 genomes lacking site I, II, and III coding sequences. Point mutations present within the site II/III coding region of Y-2-/Y-3-resistant cell lines specify the substitution of asparagine for lysine as T antigen amino acid 228 (K-2) or phenylalanine for tyrosine at position 230 (K-3). Point mutations identified within independently selected Y-5 resistant populations (K-5 and K-1,4,5) direct the substitution of isoleucine for asparagine at position 496 (K-5) or the substitution of phenylalanine for isoleucine at position 491 (K-1,4,5) of T antigen. Each substitution causes loss of the relevant CTL recognition epitope, apparently by compromising CTL T cell receptor recognition. These experiments identify specific amino acid changes within a transforming protein that facilitate transformed cell escape from site-specific CTL clones while allowing maintenance of cellular transformation. This experimental model system provides unique opportunities for studying mechanisms of transformed cell escape from active immunosurveillance in vivo, and for analysis of differential host immune responses to wild-type and mutant cell-transforming proteins.

Amino Acid Sequence↗

PubMed2002

Effects of coding dictionary on signal generation: a consideration of use of MedDRA compared with WHO-ART.

To support signal generation a terminology should facilitate recognition of medical conditions by using terms which represent unique concepts, providing appropriate, homogeneous grouping of related terms. It should allow intuitive or mathematical identification of adverse events reaching a threshold frequency or with disproportionate incidence, permit identification of important events which are commonly drug-related, and support recognition of new syndromes. It is probable that the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (PTs) or high level terms (HLTs) will be used to represent adverse events for the purposes of signal generation. A comparison with 315 WHO Adverse Reaction Terminology (WHO-ART) PTs showed that for about 72% of WHO-ART PTs, there were one or two corresponding MedDRA PTs. However, there were instances where there were many MedDRA PTs corresponding to single WHO-ART PTs. In many cases, MedDRA HLTs grouped large numbers of PTs and sometimes there could be problems when a single HLT comprises PTs which represent very different medical concepts, or conditions which differ greatly in their clinical importance. Further studies are needed to compare the way in which identical data sets coded with MedDRA and with other terminologies actually function in generating and exploring signals using the same methods of detection and evaluation.

Adverse Drug Reaction Reporting Systems↗

PubMed2005

Efficient coding of time-relative structure using spikes.

Nonstationary acoustic features provide essential cues for many auditory tasks, including sound localization, auditory stream analysis, and speech recognition. These features can best be characterized relative to a precise point in time, such as the onset of a sound or the beginning of a harmonic periodicity. Extracting these types of features is a difficult problem. Part of the difficulty is that with standard block-based signal analysis methods, the representation is sensitive to the arbitrary alignment of the blocks with respect to the signal. Convolutional techniques such as shift-invariant transformations can reduce this sensitivity, but these do not yield a code that is efficient, that is, one that forms a nonredundant representation of the underlying structure. Here, we develop a non-block-based method for signal representation that is both time relative and efficient. Signals are represented using a linear superposition of time-shiftable kernel functions, each with an associated magnitude and temporal position. Signal decomposition in this method is a non-linear process that consists of optimizing the kernel function scaling coefficients and temporal positions to form an efficient, shift-invariant representation. We demonstrate the properties of this representation for the purpose of characterizing structure in various types of nonstationary acoustic signals. The computational problem investigated here has direct relevance to the neural coding at the auditory nerve and the more general issue of how to encode complex, time-varying signals with a population of spiking neurons.

Algorithms↗

PubMed1994

A cohort model of visual word recognition.

A model of word recognition is proposed which assumes that when a word is encountered, the first available orthographic code activates all lexical entries that are positionally consistent with that information (i.e., the word's cohort). As subsequently encoded orthographic information becomes available, activation is withdrawn from lexical entries with which it is inconsistent, and the cohort is resolved when only a single candidate remains. The model is intended to characterize: (1) The initial encoding of the graphic information; (2) the recording of that information into an abstract orthographic form; (3) the manner in which the appropriate lexical entries are then activated; (4) the process whereby subsequent orthographic encoding resolves those activated entries to a single candidate; and finally (5) the way in which subjects use information for making decisions as it emerges during this processing. The model includes two critical points. The first is that letter identity information is encoded in the form of a complex orthographic unit termed a wickelgraph. A wickelgraph includes an encoding of the target letter's identity information as its core, plus, as a context, the identity of its two immediately adjacent letters. The set of possible wickelgraphs is assumed to instantiate the rules of orthography. The second point is that once a cohort is established, the perceiver can sample its status at any point during resolution and base a decision on the outcome of that sample. Some tasks (e.g., naming) may allow for a decision based on the initial status of the cohort, while others (e.g., lexical decision) can require its complete resolution. Six experiments are reported that illustrate some of these cohort effects in lexical access.

Attention↗

PubMed1992

Patterns of nucleotide substitutions inferred from the phylogenies of the class I major histocompatibility complex genes.

Patterns of nucleotide substitutions in human major histocompatibility complex (MHC) class I genes were estimated by using phylogenetic trees of DNA sequences. The pattern is defined as a set of 12 parameters, each of which represents the relative frequency of substitutions from a particular nucleotide to another. The pattern at the antigen recognition sites (ARS) in functional MHC genes was remarkably different from that at the remaining coding region (non-ARS). In particular, the proportion of transitions among all the nucleotide substitutions (Ps) was extremely low at the third codon positions of ARS. In the HLA-A genes, Ps at the third codon positions was only 6% in ARS, whereas it was 69% in non-ARS. In HLA-B, the corresponding values were 30% in ARS and 80% in non-ARS, respectively. On the other hand, Ps in a class I pseudogene (HLA-H) was 57%, which was in good agreement with Ps in other pseudogenes. Because pseudogenes are selectively neutral, the pattern in pseudogenes is regarded as the pattern of spontaneous substitution mutations. In general, the pattern in functional genes that are subject to selective forces deviates from the pattern in pseudogenes. At the third codon positions in coding regions, transitions scarcely cause amino acid replacements, whereas about half of transversions do cause replacements. Accordingly, Ps at the third codon positions decreases if amino acid replacements are accelerated by natural selection but increases if amino acids are conserved by functional constraint. Our observations imply that the ARS region is subject to natural selection favoring amino acid replacements, whereas the non-ARS region is subject to functional constraint.

Codon↗

PubMed1985

An estimate of unique DNA sequence heterozygosity in the human genome.

Fifteen different restriction fragment length polymorphisms (RFLPs) were detected in the human genome using 19 cloned DNA segments, derived from flow-sorted metaphase chromosomes or total genomic DNA, as hybridization probes. Since these clones were selected at random with respect to their coding potential, their analysis permitted an unbiased estimate of single-copy DNA sequence heterozygosity in the human genome. Since our estimate (h = 0.0037) is an order of magnitude higher than previous estimates derived from protein data, most of the polymorphic variation present in the genome must occur in non-coding sequences. In addition, it was confirmed that enzymes containing the dinucleotide CpG in their recognition sequence detect more polymorphic variation than those that do not contain CpG.

Base Sequence↗

PubMed1980

Restriction and modification in Bacillus subtilis: identification of a gene in the temperate phage SP beta coding for a BsuR specific modification methyltransferase.

A gene coding for a modifying DNA-methyltransferase which methylates the central C in the BsuR recognition sequence 5'GGCC was identified in the genome of the temperature Bacillus subtilis phage SP beta. This gene is expressed only after induction of the prophage by either mitomycin C or UV. The presence of active methyltransferase in induced cells leads to modification of BsuR recognition sites in SP beta DNA as well as in heterologous DNA.

Bacillus subtilis↗

PubMed2000

Conservation of the deleted-in-azoospermia-like-1 (DAZL1) gene structure in old world monkeys points to a homologous function of DAZL1 in this primate class.

We isolated the complete deleted-in-azoospermia-like-1 (DAZL1) gene of the old world monkey Macaca fascicularis (tentatively designated as MafaDAZL1) and compared its sequence structure to that of the other DAZL1 genes isolated so far. In addition to the homologous RNA recognition motif (RRM domain), we only identified a high conservation of the Mafa-DAZL1 coding region to the mammalian DAZL1 genes (i.e. mouse: Dazl1; and human: DAZL1) and to that of Xenopus (xdazl). Only in the primates, Macaca fascicularis and human, sequences and lengths of the 5' and 3' untranslated DAZL1 gene structures (UTRs) displayed a similar conservation as their coding regions (i.e. 91-94%). Both belong to the primate class of old world monkeys evolutionarily separated 36-55 million years ago (1). The strong conservation of the complete DAZL1 gene structure in both primate species suggests a similar control and maturation pathway of DAZL1 transcripts in the germ line of old world monkeys and also indicates a homologous function of the DAZL1 RNA-binding protein in this primate class.

3' Untranslated Regions↗

PubMed1985

In vitro packaging of plasmid DNA oligomers by Salmonella phage P22: independence of the pac site, and evidence for the termination cut in vitro.

In vitro packaging experiments with phage P22 using artificially ligated plasmid concatemers have shown that the pac site is not necessary for DNA packaging although in vivo this initiation signal is indispensable. This indicates that the phage-coded protein gp3 also executes other important functions during phage maturation in addition to the recognition of pac, or that its site specificity is lost in vitro. It has been shown previously that gp3 is necessary for in vitro packaging. Further, it was demonstrated that DNA which is only 74% of headful size cannot be packaged. Oversized DNA, however, is cut in vitro to unit length.

DNA Transposable Elements↗

PubMed2006

Density codes and shape spaces.

This paper presents an algorithm that allows for encoding probability density functions associated to samples of points of R(n). The resulting code is a sequence of points of R(n) whose density function approximates that of the set of data points. However, contrarily to sampled data points, code points associated to two different density functions can be matched, which allows to efficiently compare such functions. Moreover, the comparison of two codes can be made invariant to a wide variety of geometrical transformations of the support coordinates, provided that the Jacobian matrix of the transformation be everywhere triangular, with a strictly positive diagonal. Such invariances are commonly encountered in visual shape recognition, for example. Thus, using this tool, one can build spaces of shapes that are suitable input spaces for pattern recognition and pattern analysis neural networks. Moreover, a parallel neural implementation of the encoding algorithm is available for 2D image data.

Algorithms↗

PubMed1989

Prenatal diagnosis of platelet disorders.

The antenatal diagnosis of platelet disorders represents real progress in the early detection of haemorrhagic diseases occurring in the fetus. However, the diagnosis is only possible in some cases during the first trimester of gestation, and not in the first weeks as is the case for other hereditary disorders such as abnormal haemoglobins. This delay can be reduced now that the molecular abnormalities responsible for some platelet disorders have been discovered. If the region of chromosome 17 and the DNA sequence coding for the glycoproteins GP IIb-IIIa were known, this would make possible the recognition of the gene defect responsible for Glanzmann's thrombasthenia. This could also permit the diagnosis of Glanzmann's thrombasthenia at the gene level, i.e. during the first weeks of gestation. However, the use of gene markers could be limited by the fact that a monomorphic clinical expression of Glanzmann's thrombasthenia could correspond to different genetic mutations which can all result in a defect in GP IIb-IIIa synthesis and assembly. If such diagnosis could be made very early, it would only represent real progress if a specific treatment could be applied. New therapeutic approaches to immune thrombocytopenia during pregnancy appear to be possible and can be applied when there is a risk to the fetus, they are still either experimental or anecdotal and there is a real need for a well-designed clinical trial. In all fetal platelet disorders, the risk of fetal death following fetal blood sampling must not be underestimated and very careful, intensive care is necessary after such an investigation. In the absence of a specific therapy, this antenatal diagnosis must be restricted to cases in which the risk of severe haemorrhagic complications are anticipated and where there is a well-documented family history. The patients must be properly informed of all the aspects of the investigation, including the possible risks. As has been the case for other haematological disorders, progress will be made, and we can anticipate that eventually in utero bone-marrow transplantation or gene correction be performed to cure the disease before birth.

Autoimmune Diseases↗

PubMed1991

Assembly of a class I tRNA synthetase from products of an artificially split gene.

The aminoacyl-tRNA synthetases arose early in evolution and established the rules of the genetic code through their specific interactions with amino acids and RNA molecules. About half of these tRNA charging enzymes are class I synthetases, which contain similar N-terminal nucleotide-fold-like structures that are joined to variable domains implicated in specific protein-tRNA contacts. Here, we show that a bacterial synthetase gene can be split into two nonoverlapping segments. We split the gene for Escherichia coli methionyl-tRNA synthetase (a class I synthetase) at several sites near the interdomain junction, such that one segment codes for the nucleotide-fold-containing domain and the other provides determinants for tRNA recognition. When the segments are folded together, they can recognize and charge tRNA, both in vivo and in vitro. We postulate that an early step in the assembly of systems to attach amino acids to specific RNA molecules may have involved specific interactions between discrete proteins that is reflected in the interdomain contacts of modern synthetases.

Amino Acid Sequence↗

PubMed2006

Contrasting five different theories of letter position coding: evidence from orthographic similarity effects.

Five theories of how letter position is coded are contrasted: position-specific slot-coding, Wickelcoding, open-bigram coding (discrete and continuous), and spatial coding. These theories make different predictions regarding the relative similarity of three different types of pairs of letter strings: substitution neighbors, neighbors-once-removed, and double-substitution neighbors. In Experiment 1, we used an illusory word paradigm and found that neighbor-once-removed similarity contexts resulted in fewer illusory word reports than substitution neighbors but more illusory words than double-substitution neighbors. In Experiments 2 and 3, we used a masked form priming technique with a lexical-decision task. The pattern of facilitation was as predicted by spatial coding but was incompatible with slot-coding, Wickelcoding, and both versions of open-bigram coding. These results provide further support for the SOLAR (self-organizing lexical aquisition and recognition) model of visual word identification.

Analysis of Variance↗

PubMed2001

Non-coding RNA genes and the modern RNA world.

Non-coding RNA (ncRNA) genes produce functional RNA molecules rather than encoding proteins. However, almost all means of gene identification assume that genes encode proteins, so even in the era of complete genome sequences, ncRNA genes have been effectively invisible. Recently, several different systematic screens have identified a surprisingly large number of new ncRNA genes. Non-coding RNAs seem to be particularly abundant in roles that require highly specific nucleic acid recognition without complex catalysis, such as in directing post-transcriptional regulation of gene expression or in guiding RNA modifications.

Base Sequence↗