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Recognition of a small number of diverse epitopes dominates the cytotoxic T lymphocytes response to HIV type 1 in an infected individual.

Mitogen-activated T cell lines may be reproducibly used to identify relatively conserved HIV-1 epitopes that dominate CTL recognition of HIV-infected cells. Using a combination of nested truncations of HIV-vaccinia recombinants encoding HIV-1LAI Env and overlapping peptides that span the coding regions of the HIV-1 SF2 subclone of env, gag, nef, rev, and tat, we have mapped the immunodominant, relatively conserved CTL epitopes recognized by 25 HIV-seropositive individuals with CD4 counts between 100 and 500/mm3 and no history of AIDS opportunistic infection. We could characterize at least 1 peptide CTL epitope recognized by the T cell lines of 18 of 25 of the subjects; the T cell lines from 2 additional subjects recognized HIV-vaccinia presenting targets, but no dominant peptide epitope was identified. CTL epitopes were most frequently encoded by gag (recognized by 16 of 25 patient T cell lines), followed by nef and env (11 of 25 each), and the RT region of pol (9 of 25). Tat and Rev were rarely the sites of CTL epitopes. The identified epitopes occurred predominantly in relatively conserved regions of HIV-1. The mean number of HIV peptides identified at a single time for each cell line was 2.7 +/- 1.7. Although no single peptide dominated CTL recognition in more than four individuals, clusters of epitopes were found in the N-terminal region of gp160 and in two central regions of Nef. The dominant HIV-1 CTL epitopes in infected patients were not predictable on the basis of MHC expression and varied widely in an MHC-diverse population.

Amino Acid Sequence↗

Pattern recognition in kittens: performance on Lie patterns.

Despite a vast accumulation of knowledge about the anatomy and physiology of the cat's visual system in recent years, and about its early development, there has been very little experimental study of the development of visual behaviour in this species. This is especially true of the kitten's ability to recognize patterns. Two experiments are reported that aim to remedy some part of this deficiency, and that also serves to examine a particular hypothesis about the basis of pattern analysis in the young organism. This is Hoffman's hypothesis that the orbits of elementary Lie transformation groups (a species of continuous transformation group) represent the basis for coding pattern information.

Age Factors↗

Learning and neural plasticity in visual object recognition.

The capability of the adult primate visual system for rapid and accurate recognition of targets in cluttered, natural scenes far surpasses the abilities of state-of-the-art artificial vision systems. Understanding this capability remains a fundamental challenge in visual neuroscience. Recent experimental evidence suggests that adaptive coding strategies facilitated by underlying neural plasticity enable the adult brain to learn from visual experience and shape its ability to integrate and recognize coherent visual objects.

Animals↗

Altered DNA conformations detected by mung bean nuclease occur in promoter and terminator regions of supercoiled pBR322 DNA.

Mung bean nuclease was used to probe for recognizable DNA unwinding and unpairing in the plasmid pBR322. In negatively supercoiled DNA, but not relaxed DNA, cleavages occurred preferentially in non-coding regions of the genome. The types of nucleotide sequences cleaved and which non-coding regions were cleaved depended upon environmental conditions. At 37 degrees C, cleavages occurred in an 84 bp A+T-rich sequence in the terminator region of the ampicillin-resistance gene. Recognition is likely based on a novel DNA conformation which occurs in the longest, most dA+dT-rich region of pBR322. In the presence of 1 mM Mg2+, cleavages occurred in inverted repeated sequences in the promoter regions of the RNA primer for DNA replication and ampicillin- and tetracycline-resistance genes as well as the terminator of RNA-1. Potential loops of hairpin (cruciform) structures were cleaved. At 27 degrees C, cleavages occurred near a promoter activated by cAMP receptor protein in vitro and in the 3' non-coding region of the tetracycline-resistance gene. Thus, in supercoiled pBR322 DNA, recognizable DNA unwinding and unpairing occurs preferentially in regulatory regions for transcription and DNA replication.

Base Sequence↗

Semantic priming and repetition priming from masked words: evidence for a center-surround attentional mechanism in perceptual recognition.

Two lexical decision experiments compared semantic and repetition priming by masked words. Experiment 1 established prime-mask stimulus onset asynchronies (SOAs) with presence-absence detection judgments. Primes presented at detection-threshold SOAs produced equal facilitation for repeated and semantically related targets: 26 ms and 24 ms. Experiment 2 established SOAs with semantic judgments. Primes presented at 70% of the semantic-threshold SOA to mimic the exposure conditions of Experiment 1 produced slightly greater facilitation for repeated targets but a tendency toward inhibition for semantically related targets: 38 ms and -6 ms. These results confirm Dagenbach, Carr, and Wilhelmsen's (1989) report that strategies induced by threshold-setting tasks can influence masked priming. In addition, Experiment 2 suggests a mechanism for retrieving weakly activated semantic codes into consciousness that relies on the center-surround principle to enhance activation of sought-for codes and to inhibit related codes stored nearby in the semantic network.

Consciousness↗

A preliminary experiment on long-term memory with realistic and abstract visual patterns in uniltateral focal hemisphere-damaged patients.

Sixty-seven focal hemisphere-damaged patients (38 to the left hemisphere and 29 to the right hemisphere) were tested for forgetting of realistic and abstract visual patterns over a 40-sec to 5-min interval by means of a recognition task. No forgetting took place in any group, even if abstract patterns proved to be poorly recognized both at 40 sec and at 5 min. The authors conclude that focal neocortical unilateral lesions do not significantly hamper the semantic code processes involved in the Long-Term Memory of the patterns employed in this experiment.

Adult↗

LeRec: a NN/HMM hybrid for on-line handwriting recognition.

We introduce a new approach for on-line recognition of handwritten words written in unconstrained mixed style. The preprocessor performs a word-level normalization by fitting a model of the word structure using the EM algorithm. Words are then coded into low resolution "annotated images" where each pixel contains information about trajectory direction and curvature. The recognizer is a convolution network that can be spatially replicated. From the network output, a hidden Markov model produces word scores. The entire system is globally trained to minimize word-level errors.

Algorithms↗

Lateral masking: limitations of the feature interaction account.

Recognition performance for a target letter embedded in a string of characters is worse than that for targets presented in isolation. This lateral masking (LM) effect is known to depend on target eccentricity and spacing between target and flankers (Bouma, 1970), indicating that LM arises in early visual processing due to interactions among visual features. The feature interaction account would predict that flankers consisting of similar features produce similar LM effects and that differences in LM produced by different types of flanker diminish with increasing target eccentricity and decreasing spacing. However, in a series of six experiments, this prediction was shown not to be true. Flankers that did not access a higher level code (e.g., pseudoletters or rotated letters) produced more LM than standard letter flankers. Moreover, effects of different flanker types were most pronounced for medium target eccentricities and medium spacings for which recognition performance scores ranged between 40% and 60%.

Adult↗

Differing approaches to two-dimensional shape recognition.

This article reviews a number of approaches that perceptual psychologists have taken in attempting to understand 2-dimensional (2-D) shape recognition. Various strands in the literature are traced and current theoretical accounts are discussed in light of the earlier work. Today, it is generally accepted that the internal representation of shape is in the form of a structural description. Such a description is, in turn, couched in some form of abstract code. There is increasing interest in the notion that structural descriptions are critically determined by the imposition of a frame of reference. Although the discussion primarily deals with work on 2-D shapes, the underlying assumption is that this work is fundamental for theories of visual object recognition.

Attention↗

Three fur homologues from Anabaena sp. PCC7120: exploring reciprocal protein-promoter recognition.

DNA sequence analysis of the Anabaena sp. PCC7120 genome confirmed the presence of three open reading frames (all1691, all2473 and alr0957) containing the histidine-rich region characteristic of the Fur family. The genes coding for the three Fur proteins were cloned and overexpressed in Escherichia coli. The overexpression products, called FurA, FurB and FurC are only distantly related. The ability of the three recombinant proteins to bind iron-boxes identified in the three fur promoter regions was tested by electrophoretical mobility shift assays. FurA binds the three fur promoters with increased affinity in presence of metal. FurB also binds the three fur promoters, and its affinity is increased with DTT. FurC does not bind to furA or furB promoter regions or to its own promoter. However, FurC affects the ability of FurB and FurA to bind their target promoters.

Anabaena↗

Thermodynamic investigation of monoclonal antibody alkylated nucleoside interaction as a model for epitope recognition on nucleic acids.

The objective of this investigation is examination of the dominant forces that govern complex formation between a series of monoclonal antibodies directed against O6-ethyl-2'-deoxyguanosine. These monoclonal antibodies (coded as ER-6, ER-3, and EM-1) provide the basis for a thermodynamic comparative evaluation of the potentially different forces that stabilize the various monoclonal antibody (mAb) alkylated nucleoside complexes. The binding affinities of ER-6, ER-3, and EM-1 are measured in terms of specific (O6-ethyl-2'-deoxyguanosine, or O6-EtdGuo) and nonspecific (O6-methyl-2'-deoxyguanosine, or O6-MedGuo) antigens, under a variety of experimental conditions, including pH, sodium chloride addition, 1-propanol addition, and temperature, via a nitrocellulose affinity filter assay. The binding isotherms were analyzed via a least-squares routine fit to a two independent binding sites model. The temperature dependence of the van't Hoff enthalpies for the specific O6-EtdGuo interaction ranges from -15.18 to -18.60 kcal mol-1, while for O6-MedGuo the range was extended from -2.72 to -20.66 kcal mol-1. The standard and unitary entropies were negative for those mAb interactions with O6-EtdGuo as well as for ER-6/O6-MedGuo complex formation. However, it was found that the interactions between ER-3 and EM-1 with O6-MedGuo led to decidedly positive entropic values. These results indicate two different dominant forces at work in complex stabilization. The interaction of the three mAb's with their specific antigen, as well as ER-6/O6-MedGuo interaction (nonspecific), may well be controlled by van der Waals type forces, while ER-3 and EM-1 interactions with nonspecific antigen imply formal charge neutralization electrostatics as the dominant force.

Alkylation↗

In vivo transfer and expression of genes coding for short interfering RNAs.

RNA interference can induce potent gene silencing through degradation of complementary mRNA. Short double-stranded interfering RNAs are incorporated into an RNA-induced silencing complex that mediates the recognition and degradation of messenger RNAs in a very targeted manner. Though this phenomenon has been described in mammalian cells only a few years ago, there has been an explosion of interest in using small interfering RNAs to efficiently knockdown genes. Consequently, much effort has been put into the development of systems that allow chip and efficient delivery of these molecules into mammalian cells in vitro and in vivo. To overcome the transient inhibitory effects of transfected RNA molecule synthesis in vitro, expression plasmids, mostly based on RNA polymerase III promoters, have been designed to achieve long-term or stable inhibition of the target genes. Moreover, these expression cassettes have been incorporated into viral vectors to obtain gene silencing also in primary cells refractory to plasmid transfection, and to target specific genes in vivo in animal models. The rapid progression in the field of RNA interference has revolutionized the manner in which gene function is studied and, notably, pharmaceutical companies are already validating this technology for medical applications in the near future.

Animals↗

Hemisphere-specific effects in word recognition do not require hemisphere-specific modes of access.

Consistent with converging experimental evidence, we assume that foveal information is initially split across the two cerebral hemispheres. We have previously presented the SERIOL model of letter-position coding, which specifies how the resulting two halves of a letter string are integrated into an abstract representation of letter order. This representation is based on ordered pairs of two letters (bigrams); such a representation is created for input occurring at any location in the visual field. Various studies have shown hemisphere-specific effects in lexical access by using unilateral presentation of stimuli. While the hemisphere-independent means of lexical access in the SERIOL model (via bigrams) may seem inconsistent with these findings, we propose that such effects arise from the hemisphere-specific transformations necessary to create the bigram representation. We provide a theoretical account of the finding that high N (lexical neighborhood size) evokes facilitation in the RH, but not the LH (Lavidor & Ellis, 2002a, 2002b); an experiment discussed elsewhere (Whitney & Lavidor, 2003) has verified key predictions of this account. We also discuss the differing effects of word length across visual fields.

Brain↗

Effect of image scrambling on inferior temporal cortical responses.

Imaging studies compared activations elicited by images of objects and scrambled versions of these same images in order to localize human brain regions involved in object recognition. Given these studies and the known role of macaque temporal cortex in object recognition, I determined the effect of image scrambling on the responses of macaque inferior temporal neurons. Images of natural objects were scrambled to different degrees. The response of most neurons decreased with increasing degrees of scrambling. In 26% of the neurons, response was reduced by 50% when the image was scrambled using only four parts, but most neurons tolerated higher degrees of scrambling, suggesting that these neurons code object parts instead of entire objects. These results are related to human functional imaging studies.

Action Potentials↗

Structural basis for recognition of the RNA major groove in the tau exon 10 splicing regulatory element by aminoglycoside antibiotics.

Drug-like molecules that bind RNA with sequence selectivity would provide valuable tools to elucidate gene expression pathways and new avenues to the treatment of degenerative and chronic conditions. Efforts at discovering such agents have been hampered, until recently, by the limited knowledge of RNA recognition principles. Several recent structures of aminoglycoside-RNA complexes have begun to reveal the structural basis for RNA-drug recognition. However, the absence of suitable chemical scaffolds known to bind the RNA major groove, where specificity could be provided by the diversity of functional groups exposed on the RNA bases, has represented a major obstacle. Here we report an investigation of the structural basis for recognition of an RNA stem-loop by neomycin, a naturally occurring aminoglycoside antibiotic. We found that neomycin binds the RNA stem-loop that regulates alternative splicing of exon 10 within the gene coding for human tau protein. Mutations within this splicing regulatory element destabilise the RNA structure and cause frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17), an autosomal dominant condition leading to neurodegeneration and death. The three-dimensional structure of the RNA-neomycin complex shows interaction of the drug in the major groove of the short RNA duplex, where familial mutations cluster. Analysis of the structure shows how aminoglycosides and related drugs bind to the RNA major groove, adding to our understanding of the principles of drug-RNA recognition.

Anti-Bacterial Agents↗

Effects of hemispheric laterality on color-information processing.

This study investigated the interaction between hemispheric laterality and recognition memory for pictures presented in three different color modes: realistic, nonrealistic, and monochrome (black and white). Stimulus materials were 180 scenic slides (120 stimulus and 60 distractor) produced in three color modes. Materials were presented to a group of 26 graduate volunteers via the list learning procedure for a duration of 500 msec. each. During one-half of the materials an arithmetic masking task was performed to inhibit left-hemisphere processing. Signal-detection parameters, compared in a 2 x 3 repeated-measures design, produced significant interactions for the probability of hits, error, and d' measures. Post hoc tests indicated significantly higher hit probability and d' scores for nonrealistic color and higher error rates for realistic color under the right localized condition. Findings suggest that color processing is bilocational, realistic information is processed more deeply than nonrealistic, and nonrealistic color supplies unique color codes for storage and retrieval.

Adult↗

DNA deletion confined to the iduronate-2-sulfatase promoter abolishes IDS gene expression.

Deficiency of the enzyme iduronate-2-sulfatase (IDS) results in Hunter syndrome, an X-linked recessive lysosomal storage disorder. In this study, analysis of a patient with features of moderate to severe Hunter syndrome identified a 178-bp deletion upstream of IDS exon 1 spanning a predicted promoter element. Sequencing of all nine IDS exons from this patient failed to identify any additional mutations within the coding regions or in intron-exon boundaries. The 178-bp deletion is flanked by two 13-bp direct repeats and potential DNA topoisomerase II recognition sites. These findings point toward nonhomologous recombination as a possible mechanism for this mutation. Expression studies on this patient do not detect any IDS transcripts, indicating that the deletion spans sequences essential for IDS expression. Complete lack of expression of IDS is consistent with the moderate to severe phenotype observed in this patient.

Base Sequence↗

Visual neurones responsive to faces in the monkey temporal cortex.

Of 497 single neurones recorded in the cortex in the fundus of the superior temporal sulcus (STS) of three alert rhesus monkeys, a population of at least 48 cells which were selectively responsive to faces had the following response properties: (1) The cells' responses to faces (real or projected, human or rhesus monkey) were two to ten times as large as those to gratings, simple geometrical stimuli or complex 3-D objects. (2) Neuronal responses to faces were excitatory, sustained and were time-locked to the stimulus presentation with a latency of between 80 and 160 ms. (3) The cells were unresponsive to auditory or tactile stimuli and to the sight of arousing or aversive stimuli. (4) The magnitude of the responses of 28 cells tested was relatively constant despite transformations, such as rotation, so that the face was inverted or horizontal, and alterations of colour, size or distance. (5) Rotation to profile substantially reduced the responses of 21 cells (31 tested). (6) Masking out or presenting parts of the face (i.e. eyes, mouth or hair) in isolation revealed that different cells responded to different features or subsets of features. (7) For several cells, responses to the normal organisation of cut-out or line-drawn facial features were significantly larger than to jumbled controls. These findings indicate that explanations in terms of arousal, emotional or motor reactions, simple visual feature sensitivity or receptive fields are insufficient to account for the selective responses to faces and face features observed in this population of STS neurones. It appears that these neurones are part of a system specialised to code for faces or features present in faces, and it is suggested that damage to this system is related to prosopagnosia, or difficulty in face recognition, in man and to the tameness and social disturbances which follow temporal lobe damage and are part of the Klüver-Bucy syndrome in the monkey.

Animals↗