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Recognition of HLA-A2 by cytotoxic T lymphocytes after DNA transfer into human and murine cells.

A gene coding for the major histocompatibility antigen HLA-A2 was transferred into human HLA-A2 negative M1 cells and murine L cells. Following transfection, these cells expressed molecules at the cell surface that are biochemically indistinguishable from HLA-A2 antigens on the human cell line JY from which the HLA-A2 gene was isolated. The M1A2 cells were recognized and lysed by a cytolytic T-cell clone specific for HLA-A2. The transfected L cells which express HLA-A2 in association with human beta 2-microglobulin were not lysed by this T-cell clone. The specific cytolysis of M1A2 cells could be inhibited by monoclonal antibodies to HLA-A2, and monoclonal antibodies to T3, T8, and LFA-1 on cytotoxic T lymphocytes. These results suggest that killing by allospecific T cells requires HLA-A2 antigens as well as other species-specific structures on the target cell surface.

Animals↗

[The effect of impression formation on memory of trait words: relation between coding and retrieval process].

Three experiments investigated the effect of impression formation of a person on the recall and recognition of trait words. The subjects were assigned to one of four groups: Impression, Memory, Impression-Memory, and Incidental groups. Each subject performed an orienting task followed by free recall and recognition tests. In a recall test, false recall of antonyms of targets occurred more often in the Memory group than in the Impression group. There was no difference in the correct recall. In a multiple choice recognition test and a yes-no recognition test, false recognition to antonyms of targets occurred more often in the Memory group than in the Impression group. Hit to targets occurred more often in the Impression group than in the Memory group. These results were interpreted as showing that formation of an impression for a person had different effects for recall and recognition tests. The results were discussed in terms of a relation between encoding and retrieval processes.

Adult↗

Recognition of damaged regions in DNA by oligopeptides and proteins.

The binding of various damaged DNAs to the single-strand binding protein coded for by gene 32 from bacteriophage T4, on the one hand, and of oligopeptides containing tryptophan and lysine residues, on the other hand, is described. These molecules exhibit a higher affinity for modified DNA than for native DNA in so far as modification results in a local destabilization of the double-stranded structure of the nucleic acid. Stacking interactions between aromatic amino acids and nucleic acid bases appear to play a crucial role in the recognition of destabilized regions induced by chemical agents (carcinogens and antitumor drugs). These interactions confer to the peptide lysyl-tryptophyl-lysine an endonucleolytic activity specific for apurinic sites. From results obtained with such oligopeptides a model for the active sites of Ap-endonucleases is proposed which could account for the strategy used by the denV endonuclease from phage T4 during the first step of excision repair of pyrimidine dimers in DNA. The effect of the overall conformation of modified DNA on repair efficiency is discussed.

Amino Acids↗

Speech perception with the ACE and the SPEAK speech coding strategies for children implanted with the Nucleus cochlear implant.

OBJECTIVE: The aim of this study is to determine whether implanted children using the ACE speech coding strategy demonstrate superior performances compared to implanted children using the SPEAK speech coding strategy over time. METHODS: Cochlear implanted children with prelinguistic sensorineural bilateral deafness of profound degree, using either the ACE or SPEAK coding strategy, were evaluated and compared. Both groups of children used one of the speech coding strategies continuously from the initial programming session and for a period of 2 years post-switch-on. One group comprised children who were retrospectively implanted and had received the SPEAK speech coding strategy (n=32) and the second group consisted of prospectively implanted children who received the ACE speech coding strategy (n=26). Both populations were homogenous as far as age of implantation, degree of hearing loss, anatomy of the cochlea, depth of electrode insertion, and educational and rehabilitative support provided. Children were assessed at 6, 12 and 24 months post switch-on via pure-tone audiometry and for speech perception tests. Children using the ACE speech coding strategy were additionally evaluated using the MAIS and MUSS language scales. RESULTS: Satisfactory benefits in speech perception were demonstrated by both groups of implanted children. No significant difference between the mean pure tone thresholds was observed postoperatively between the groups. Two years post switch-on the group using the ACE speech coding strategy demonstrated superior results for vowel discrimination in comparison to children using the SPEAK coding strategy. No significant difference was observed between the groups for performance on discrimination of syllable patterns (ESP) or for disyllablic word recognition tests. Additionally, the group of ACE users demonstrated maximum performance on MAIS and MUSS scales, 2 years post switch-on. CONCLUSIONS: The results clearly demonstrate significant benefit of cochlear implantation in prelinguistically deafened children for speech perception ability when using either the SPEAK or ACE speech coding strategies. Children using the ACE speech coding strategy demonstrate more rapid progress in improved speech perception ability initially, however 2 years post switch-on, no significant difference in performance on open-set speech recognition tests can be noted irrespective of the strategy in use.

Audiometry, Pure-Tone↗

Speech recognition experience with multichannel cochlear implants.

Four patients received multichannel intracochlear implants before 1978 as part of the University of Utah program. By 1983, sound coding strategies and electronic miniaturization were developed to allow production and use of a portable sound processor/cochlear stimulator unit. Approval for expanded clinical trials has allowed implantation of five additional patients by August 1984. Data on the earlier patients demonstrate stability of electrode thresholds and impedance, low risk of the percutaneous pedestal, and the development of speech recognition scores of greater than 60% with electrical stimulation alone and greater than 90% with electrical stimulation combined with lipreading. Data on recent recipients indicate early electrode threshold stability, lower thresholds for apical electrodes, possibility of replacing single-channel with multi-channel units, and low morbidity of the implantation. Return to function in a verbally communicating environment has been achieved by one earlier patient.

Adult↗

Effect of blank time on picture recognition.

An experiment was conducted to evaluate the effect of blank time between picture presentations on retention of two types of picture information: specific detail information and general visual information. A series of slides of "everyday" scenes was presented, and the blank time between slide presentations was varied. After presentation of the series of slides, memory for specific details and general visual information was probed using a forced-choice testing procedure. Although previous research failed to find blank-time effects using similar stimuli, it was thought that by keeping both slide presentation times and blank times constant within each experimental block, an effect of blank time might be found. The results indicated that retention of both specific details and general visual information was aided by the extra rehearsal opportunity afforded by longer blank times; there was no interaction between the type of information probed and the duration of blank time. It is suggested that because the blank-time variable affected retention of specific detail and general visual information equally, the two types of information may be held by a common coding system.

Form Perception↗

Isolation and expression of two genes encoding eukaryotic release factor 1 from Paramecium tetraurelia.

Paramecium tetraurelia, like some other ciliate species, uses an alternative nuclear genetic code where UAA and UAG are translated as glutamine and UGA is the only stop codon. It has been postulated that the use of stop codons as sense codons is dependent on the presence of specific tRNAs and on modification of eukaryotic release factor one (eRF1), a factor involved in stop codon recognition during translation termination. We describe here the isolation and characterisation of two genes, eRF1-a and eRF1 b, coding for eRF1 in P. tetraurelia. The two genes are very similar, both in genomic organization and in sequence, and might result from a recent duplication event. The two coding sequences are 1,314 nucleotides long, and encode two putative proteins of 437 amino acids with 98.5% identity. Interestingly, when compared with the eRF1 sequences either of ciliates having the same variant genetic code, or of other eukaryotes, the eRF1 of P. tetraurelia exhibits significant differences in the N-terminal region, which is thought to interact with stop codons. We discuss here the consequences of these changes in the light of recent models proposed to explain the mechanism of stop codon recognition in eukaryotes. Besides, analysis of the expression of the two genes by Northern blotting and primer extension reveals that these genes exhibit a differential expression during vegetative growth and autogamy.

Amino Acid Sequence↗

The evolving tRNA molecule.

The study of tRNA molecular evolution is crucial to understanding the origin and establishment of the genetic code as well as the differentiation and refinement of the machinery of protein synthesis in prokaryotes, eukaryotes, organelles, and phage systems. The small size of the molecule and its critical involvement in a multiplicity of roles distinguish its study from classical protein molecular evolution with respect to goals and methods. Here, the authors assess available and missing data, existing and needed methodology, and the impact of tRNA studies on current theories both of genetic code evolution and of the evolution of species. They analyze mutational "hot spots", the role of base modification, synthetase recognition, codon-anticodon interactions and the status of organelle tRNA.

Animals↗

Characterization of a second human pulmonary surfactant-associated protein SP-A gene.

Pulmonary surfactant is a lipid-protein complex involved in maintaining alveolar stability. SP-A is the major surfactant-associated protein of 26 to 38 kD. A human SP-A gene (SP-A I) and two distinct SP-A cDNAs, MPSAP 1A and MPSAP 6A, have been reported previously. We have isolated and characterized a second human SP-A gene (SP-A II), which appears to code for the mRNA corresponding to the previously described MPSAP-1A cDNA. Both genes consist of five exons, a consensus recognition sequence for initiation, TATAAA, and a polyadenylation signal sequence. Significant divergence in the two genes is observed throughout. The divergence is highest in the upstream region, intron I, exon III, and noncoding portion of exon V. The coding regions of all other exons and the introns show much lower divergence. Transcripts from both genes were found in adult human lung, using gene-specific oligonucleotide probes in Northern blot analysis.

Amino Acid Sequence↗

Automated coding of patient discharge summaries using conceptual graphs.

In medicine, as in other domains, indexing and classification is a natural human task which is used for information retrieval and representation. In the medical field, encoding of patient discharge summaries is still a manual time-consuming task. This paper describes an automated coding system of patient discharge summaries from the field of coronary diseases into the ICD-9-CM classification. The system is developed in the context of the European AIM MENELAS project, a natural-language understanding system which uses the conceptual-graph formalism. Indexing is performed by using a two-step processing scheme; a first recognition stage is implemented by a matching procedure and a secondary selection stage is made according to the coding priorities. We show the general features of the necessary translation of the classification terms in the conceptual-graph model, and for the coding rules compliance. An advantage of the system is to provide an objective evaluation and assessment procedure for natural-language understanding.

Artificial Intelligence↗

Intact aminoacyl-tRNA is required to trigger GTP hydrolysis by elongation factor Tu on the ribosome.

GTP hydrolysis by elongation factor Tu (EF-Tu) on the ribosome is induced by codon recognition. The mechanism by which a signal is transmitted from the site of codon-anticodon interaction in the decoding center of the 30S ribosomal subunit to the site of EF-Tu binding on the 50S subunit is not known. Here we examine the role of the tRNA in this process. We have used two RNA fragments, one which contains the anticodon and D hairpin domains (ACD oligomer) derived from tRNA(Phe) and the second which comprises the acceptor stem and T hairpin domains derived from tRNA(Ala) (AST oligomer) that aminoacylates with alanine and forms a ternary complex with EF-Tu. GTP. While the ACD oligomer and the ternary complex containing the Ala-AST oligomer interact with the 30S and 50S A site, respectively, no rapid GTP hydrolysis was observed when both were bound simultaneously. The presence of paromomycin, an aminoglycoside antibiotic that binds to the decoding site and stabilizes codon-anticodon interaction in unfavorable coding situations, did not increase the rate of GTP hydrolysis. These results suggest that codon recognition as such is not sufficient for GTPase activation and that an intact tRNA molecule is required for transmitting the signal created by codon recognition to EF-Tu.

Anticodon↗

A neural model of predictive recognition in form pathway of visual cortex.

We present a functional model of form pathway in visual cortex based on predictive coding scheme, in which the prediction is compared with feedforward signals filtered by two kinds of spatial resolution maps, broad and fine resolution map. We propose here the functional role of the prediction and of the two kinds of resolution maps in perception of object form in visual system. The prediction is represented based on memory of dynamical attractors in temporal cortex, categorized by an elemental figure in posterior temporal cortex. The prediction is generated by the feedforward signals of main neurons in broad resolution maps of V(1) and V(4), and then is compared with the feedforward signals of main neurons in fine resolution map of V(1) and V(4).

Animals↗

Some principles in the brain analysis of important signals: mapping and stimulus recognition.

This essay addresses two questions: What are the meanings of different kinds of brain maps? Can the recognition of important communicative signals and other stimuli known to the system be adequately explained by an ensemble code? Several kinds and grades of brain maps are distinguished. Before we can properly state the meaning, especially of the higher forms of multiple and multifactor maps, we need to learn where they project. At the higher levels this is a labor-intensive task, requiring also ingenuity and ethological thinking to devise stimuli. The neuronal basis of recognition in those cases where behavior or perception is triggered in an either-or manner has chiefly been attributed to one or the other of two classes of models: a large spatiotemporal configuration of many kinds of cells in which there is little convergence of input, and a small set of nearly equivalent cells after successive convergences. The latter is known to exist but it is not clear how far it goes or for what classes of stimuli. The former is a more popular view but carries several burdens in required assumptions and is essentially not demonstrable or disprovable. I believe both exist and operate in sequence: specific ensembles are inputs to small sets of equivalent recognition units and specific arrays of different recognition units at higher and higher levels of abstraction may constitute the specific configurations for the most sophisticated recognitions. Our information base is pitifully small, especially in comparative physiology of higher integrative functions of the brain and in comparative behaviour.

Afferent Pathways↗

Active and dynamic information fusion for facial expression understanding from image sequences.

This paper explores the use of multisensory information fusion technique with Dynamic Bayesian networks (DBNs) for modeling and understanding the temporal behaviors of facial expressions in image sequences. Our facial feature detection and tracking based on active IR illumination provides reliable visual information under variable lighting and head motion. Our approach to facial expression recognition lies in the proposed dynamic and probabilistic framework based on combining DBNs with Ekman's Facial Action Coding System (FACS) for systematically modeling the dynamic and stochastic behaviors of spontaneous facial expressions. The framework not only provides a coherent and unified hierarchical probabilistic framework to represent spatial and temporal information related to facial expressions, but also allows us to actively select the most informative visual cues from the available information sources to minimize the ambiguity in recognition. The recognition of facial expressions is accomplished by fusing not only from the current visual observations, but also from the previous visual evidences. Consequently, the recognition becomes more robust and accurate through explicitly modeling temporal behavior of facial expression. In this paper, we present the theoretical foundation underlying the proposed probabilistic and dynamic framework for facial expression modeling and understanding. Experimental results demonstrate that our approach can accurately and robustly recognize spontaneous facial expressions from an image sequence under different conditions.

Algorithms↗

Random oligonucleotide mutagenesis: application to a large protein coding sequence of a major histocompatibility complex class I gene, H-2DP.

We have used random oligonucleotide mutagenesis (or saturation mutagenesis) to create a library of point mutations in the alpha 1 protein domain of a Major Histocompatibility Complex (MHC) molecule. This protein domain is critical for T cell and B cell recognition. We altered the MHC class I H-2DP gene sequence such that synthetic mutant alpha 1 exons (270 bp of coding sequence), which contain mutations identified by sequence analysis, can replace the wild type alpha 1 exon. The synthetic exons were constructed from twelve overlapping oligonucleotides which contained an average of 1.3 random point mutations per intact exon. DNA sequence analysis of mutant alpha 1 exons has shown a point mutant distribution that fits a Poisson distribution, and thus emphasizes the utility of this mutagenesis technique to "scan" a large protein sequence for important mutations. We report our use of saturation mutagenesis to scan an entire exon of the H-2DP gene, a cassette strategy to replace the wild type alpha 1 exon with individual mutant alpha 1 exons, and analysis of mutant molecules expressed on the surface of transfected mouse L cells.

Amino Acid Sequence↗

Physical map of the Bombyx mori DNA containing the gene for silk fibroin.

A physical map of the DNA containing the gene for silk fibroin was developed from direct hybridization analysis of restriction endonuclease digests of total Bombyx mori DNA using fibroin 125I-mRNA. The orientation of mRNA transcription relative to this map was deduced from the sensitivity of the mRNA coding strand within certain DNA restriction segments to lambda-exonuclease and exonuclease III. The map includes the entire gene coding region (Mr approximately 11 x 10(6)) and large DNA elements which flank the gene at its 5' end (Mr approximately 3 x 10(6)) and 3' end (Mr approximately 6.5 x 10(6)). The coding region is remarkably uniform in its sensitivity to restriction endonucleases. It is completely devoid of sites for most of the enzymes tested, including Hae III, the recognition sequence (d-pG-G C-C) of which might be expected to occur frequently in this large DNA block of 60% G + C content. The fibroin coding region does contain an enormous number of sites for enzymes predicted to have activity from known fibroin mRNA sequences. These results suggeste that the fibroin gene core is a large homogeneously repetitive block of DNA with little evidence for sequence divergence, or the presence of qualitatively different sequences, which might creat other restriction sensitivities. The map also allowed a comparison to be made of the fibroin gene "context" in DNA from tissues either active or inactive in fibroin synthesis.

Animals↗

Antimicrobial peptides from amphibian skin: what do they tell us?

Amphibian skin secretions contain many biologically active compounds, such as biogenic amines, complex alkaloids, or peptides. Within the latter class of molecules, a large number of peptide antibiotics has been isolated and characterized from different amphibian species. Antimicrobial peptides are considered the effector molecules of innate immunity, acting as a first line of defense against bacterial infections, by perturbing the phospholipid bilayer of the target cell membrane. These gene-encoded molecules are synthesized as inactive precursors and in several cases their proparts were shown to have highly conserved structures. It has also been demonstrated that the promoter regions of inducible peptide antibiotics are often regulated by the transcriptional control machinery NF-kappa B/I kappa B alpha. In amphibia of Rana and Bombina genera, inhibition of transcription of the genes encoding antimicrobial peptides has been obtained by glucocorticoid treatment, which causes an increase of I kappa B alpha synthesis. Moreover, determination of the structure of a number of genes coding for antimicrobial peptides in amphibia has actually shown that their promoter regions contain recognition sites for nuclear factors.

Amino Acid Sequence↗

Identification of cis-acting DNA sequences involved in the transcription of the virulence regulatory gene spvR in Salmonella typhimurium.

The SpvR protein is a DNA-binding protein of the LysR family, required for the transcription of the spvABCD virulence operon of Salmonella typhimurium. An alternative sigma factor, sigma S (RpoS), in conjunction with SpvR, controls the transcription of the spvR gene. In this study, we used a combination of primer extension experiments and deletion/fusion analyses of the spvR gene to identify sequences involved in spvR transcription in S. typhimurium. When induced in the stationary phase of growth in rich medium or during carbon starvation, transcription of spvR in S. typhimurium is driven by a single promoter (spvRp1) and initiates 17 nucleotides upstream of the spvR start codon. The level of spvR transcription originating at spvRp1 was 20-fold higher in the wild-type strain than in the rpoS mutant. In both strains, however, transcription at spvRp1 requires the SpvR protein. 5' Deletions up to position -86, relative to the spvR start codon, did not inhibit inducibility by sigma S and/or SPVR. In contrast, 5' deletion up to -75 abolished the activation of spvRp1 by SpvR in both the wild-type strain and rpoS mutant. Within the 11-bp sequence lying between position -86 and position -75, a 10-bp consensus motif TNTNTGCANA, present in both the spvR and spvA promoter regions, was identified and may contain the DNA recognition site for SpvR. In addition, we detected initiation of transcription within the spvR coding region. This finding may have implications for comparative studies of regulation with spvR gene fusions.

Bacterial Proteins↗