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Lexical activation produces potent phonemic percepts.

Theorists disagree about whether auditory word recognition is a fully bottom-up, autonomous process, or whether there is top-down processing within a more interactive architecture. The current study provides evidence for top-down lexical to phonemic activation. In several experiments, listeners labeled members of a /bI/-/dI/ test series, before and after listening to repeated presentations of various adapting sounds. Real English words (containing either a /b/ or a /d/) produced reliable adaptation shifts in labeling of the /bI/-/dI/ syllables. Critically, so did words in which the /b/ or /d/ was perceptually restored (when noise replaced the /b/ or /d/). Several control conditions demonstrated that no adaptation occurred when no phonemic restoration occurred. Similarly, no independent role in adaptation was found for lexical representations themselves. Thus, the results indicate that lexical activation can cause the perceptual process to synthesize a highly functional phonemic code. This result provides strong evidence for interactive models of word recognition.

Analysis of Variance↗

Memory representation within the parahippocampal region.

The activity of 378 single neurons was recorded from areas of the parahippocampal region (PHR), including the perirhinal and lateral entorhinal cortex, as well as the subiculum, in rats performing an odor-guided delayed nonmatching-to-sample task. Nearly every neuron fired in association with some trial event, and every identifiable trial event or behavior was encoded by neuronal activity in the PHR. The greatest proportion of cells was active during odor sampling, and for many cells, activity during this period was odor selective. In addition, odor memory coding was reflected in two general ways. First, a substantial proportion of cells showed odor-selective activity throughout or at the end of the memory delay period. Second, odor-responsive cells showed odor-selective enhancement or suppression of activity during stimulus repetition in the recognition phase of the task. These data, combined with evidence that the PHR is critical for maintaining odor memories in animals performing the same task, indicate that this cortical region mediates the encoding of specific memory cues, maintains stimulus representations, and supports specific match-nonmatch judgments critical to recognition memory. By contrast, hippocampal neurons do not demonstrate evoked or maintained stimulus-specific codings, and hippocampal damage results in little if any decrement in performance on this task. Thus it becomes increasingly clear that the parahippocampal cortex can support recognition memory independent of the distinct memory functions of the hippocampus itself.

Animals↗

UTY gene codes for an HLA-B60-restricted human male-specific minor histocompatibility antigen involved in stem cell graft rejection: characterization of the critical polymorphic amino acid residues for T-cell recognition.

Rejection of a graft after human leukocyte antigen (HLA)-identical stem cell transplantation (SCT) can be caused by recipient's immunocompetent T lymphocytes recognizing minor histocompatibility antigens on donor stem cells. During rejection of a male stem cell graft by a female recipient, 2 male (H-Y)-specific cytotoxic T lymphocyte (CTL) clones were isolated from peripheral blood. One CTL clone recognized an HLA-A2-restricted H-Y antigen, encoded by the SMCY gene. Another CTL clone recognized an HLA-B60-restricted H-Y antigen. In this study UTY was identified as the gene coding for the HLA-B60-restricted H-Y antigen. The UTY-derived H-Y antigen was characterized as a 10-amino acid residue peptide, RESEEESVSL. Although the epitope differed by 3 amino acids from its X-homologue, UTX, only 2 polymorphisms were essential for recognition by the CTL clone HLA-B60 HY. These results illustrate that CTLs against several H-Y antigens derived from different proteins can contribute simultaneously to graft rejection after HLA-identical, sex-mismatched SCT. Moreover, RESEEESVSL-specific T cells could be isolated from a female HLA-B60+ patient with myelodysplastic syndrome who has been treated with multiple blood transfusions, but not from control healthy HLA-B60+ female donors. This may indicate that RESEEESVSL-reactive T cells are more common in sensitized patients.

Base Sequence↗

Gypsy/Ty3-class retrotransposons integrated in the DNA of herring, tunicate, and echinoderms.

Eight new examples of retrotransposons of the Gypsy/Ty3 class have been identified in marine species. A 525-nt pol gene-coding region was amplified using degenerate primers from highly conserved regions and has extended the range of recognition of Gypsy/Ty3 far beyond those previously known. The following matrix shows the percentage AA divergence of the translations of this segment of the pol gene coding region. [table: see text] The underlines separate three groups of retrotransposons that can be recognized on the basis of this amino acid sequence. The new upper group shows surprising amino acid sequence similarity among members from the DNA of herring, sea urchin, starfish, and a tunicate. For example, the herring element differs by only 41% from the Ciona element and 46% from the sea urchin element. The group between the lines includes members close to previously known elements (marked by asterisks) and has so far been found only in sea urchins. The two upper groups differ from each other by 55-60% and yet members of both groups (e.g., Spr1 and Spr2) are integrated into the DNA of one species--S. purpuratus. Below the lower underline is listed the only known representative of a very distant group, which occurs in starfish DNA. In spite of large divergence, amino acid sequence comparisons indicate that all of the elements shown in the array are members of the LTR-containing class of retrotransposons that includes Gypsy of Drosophila and Ty3 of yeast. Of all known mobile elements this class shows the closest sequence similarity to retroviruses and has the same arrangement of genes as simpler retroviruses.

Amino Acid Sequence↗

Synthesis and sequence-specific proteolysis of a hybrid protein (colicin A::growth hormone releasing factor) produced in Escherichia coli.

DNA constructs coding for human growth hormone (hGH)-releasing factor (hGRF) preceded by the specific recognition sequence for the activated blood coagulation factor X (FXa), fused in frame to the N-terminal 172-amino acid residues of colicin A, have been expressed in Escherichia coli. The construct was placed under the control of the inducible caa promoter in an operon containing a downstream gene coding for the cell lysis protein, Cal. Induction resulted in excretion of only the processed colicin A fragment. Replacement of Cal by the terminator from phage fd resulted in high expression of the hybrid protein, which was recovered as cytoplasmic aggregates. Enzymatic cleavage of the purified and renatured hybrid protein using FXa allowed the recovery of authentic hGRF.

Base Sequence↗

Major histocompatibility complex of the mole-rat. II. Restriction fragment polymorphism.

The major histocompatibility complex (Mhc) is a group of loci coding for lymphocyte membrane glycoproteins that provide the context for the recognition of foreign antigens in the initial phase of the immune response. The complex contains a large number of loci, some of which are highly polymorphic. The complexity and polymorphism pose a number of questions concerning the evolution of the Mhc. In an attempt to answer some of these questions, we have begun to study the Mhc of the mole-rat, Spalax ehrenbergi, a rodent representing a complex of sibling species occupying ecologically and geographically clearly delineated regions within the borders of Israel. In an earlier publication we identified the Spalax major histocompatibility (Smh) complex serologically and biochemically. Here, we analyze the Smh by Southern blotting of DNA fragments produced by restriction enzyme digestion. The fragments were hybridized to mouse probes specific for class I, class II, and C4 genes. The analysis has revealed that the Smh complex contains as many class I genes as the mouse does and that these genes are polymorphic. The number of class II genes could not be determined with certainty, but it is probably not greater than in the mouse. Polymorphism was also detected at the loci coding for the complement component 4 (C4), which are probably closely linked to the Smh complex. The polymorphism of mole-rat class I loci contrasts with the reported monomorphism of these loci in the Syrian hamster. Since the mole-rat leads a solitary, subterranean life, as the Syrian hamster does, ecology cannot be an explanation for the lack of class I polymorphism in the latter species.

Animals↗

Age differences in primary organization or processing variability? Part II: Evidence for processing variability.

Young and older adults were compared on their ability to organize letter sets into "opaque" memory codes (letters were either transposed within or between imposed chunk boundaries on a secondary memory, recognition task). Also, processing variability (i.e., internal noise) was examined via signal detection methods. The data indicated that there were no qualitative age differences in the manner in which both groups organized opaque memory codes, although older adults did take significantly longer to respond. The results from the signal detection theory portion of the present experiment demonstrated that older adults' memory operating characteristic curves exhibited significantly more variability than those of the young. This suggested that an age difference in processing variability existed, rather than any appreciable age difference in the primary organization (i.e., the forming of opaque memory codes) of item order information.

Adolescent↗

Different modes of word recognition in the left and right visual fields.

We confirm previous evidence indicating that word length has a substantial effect on word recognition in the LVF but a much weaker effect in both the RVF and fovea. The nature of encoding in the LVF is not altered when the words are vertically displayed (Experiment 2), and the effect cannot therefore be entirely due to scanning artefact or acuity gradients in peripheral vision. We provide evidence that links the asymmetrical influence of word length directly to hemispheric specialization: left-handers, who as a group are much less consistently lateralized than right-handers are also less affected by word length in the LVF on the average (Experiment 3). This occurs because the asymmetry for certain left-handers is either very weak or, in some cases, is the complete reverse of the asymmetry observed in right-handers. Finally, we demonstrate that the length x field interaction is observed in lexical decisions (Experiment 4) which do not entail pronunciation of written words. There is some indication that concrete, high-imageable words produce a smaller effect of length in the LVF than abstract, low-imageable words, and we discuss this outcome in relation to the proposal that the right hemisphere can sometimes extract a lexical code from letter information. The concept of distinct modes of word recognition in the LVF and RVF clarifies a number of issues in laterality research, and suggests a new approach to evaluating group differences in half-field performance.

Adult↗

Wavelet-based processing of neuronal spike trains prior to discriminant analysis.

Investigations of neural coding in many brain systems have focused on the role of spike rate and timing as two means of encoding information within a spike train. Recently, statistical pattern recognition methods, such as linear discriminant analysis (LDA), have emerged as a standard approach for examining neural codes. These methods work well when data sets are over-determined (i.e., there are more observations than predictor variables). But this is not always the case in many experimental data sets. One way to reduce the number of predictor variables is to preprocess data prior to classification. Here, a wavelet-based method is described for preprocessing spike trains. The method is based on the discriminant pursuit (DP) algorithm of Buckheit and Donoho [Proc. SPIE 2569 (1995) 540-51]. DP extracts a reduced set of features that are well localized in the time and frequency domains and that can be subsequently analyzed with statistical classifiers. DP is illustrated using neuronal spike trains recorded in the motor cortex of an awake, behaving rat [Laubach et al. Nature 405 (2000) 567-71]. In addition, simulated spike trains that differed only in the timing of spikes are used to show that DP outperforms another method for preprocessing spike trains, principal component analysis (PCA) [Richmond and Optican J. Neurophysiol. 57 (1987) 147-61].

Action Potentials↗

cis-trans recognition and subunit-specific degradation of short-lived proteins.

The N-end rule, a code that relates the metabolic stability of a protein to the identity of its amino-terminal residue, is universal in that different versions of the N-end rule operate in mammals, yeast and bacteria (unpublished data). The N-end rule-based degradation signal comprises a destabilizing amino-terminal residue and a specific internal lysine residue. We now show that, in a multisubunit protein, these two determinants can be located on different subunits and still target the protein for destruction. Moreover, in this case (trans recognition) only the subunit that bears the lysine determinant is actually degraded. Thus an oligomeric protein can contain both short-lived and long-lived subunits. These insights have functional and practical implications.

Amino Acid Sequence↗

Auditory word recognition: extrinsic and intrinsic effects of word frequency.

Two experiments investigated the influence of word frequency in a phoneme identification task. Speech voicing continua were constructed so that one endpoint was a high-frequency word and the other endpoint was a low-frequency word (e.g., best-pest). Experiment 1 demonstrated that ambiguous tokens were labeled such that a high-frequency word was formed (intrinsic frequency effect). Experiment 2 manipulated the frequency composition of the list (extrinsic frequency effect). A high-frequency list bias produced an exaggerated influence of frequency; a low-frequency list bias showed a reverse frequency effect. Reaction time effects were discussed in terms of activation and postaccess decision models of frequency coding. The results support a late use of frequency in auditory word recognition.

Acoustic Stimulation↗

Recognition of unknown conserved alternatively spliced exons.

The split structure of most mammalian protein-coding genes allows for the potential to produce multiple different mRNA and protein isoforms from a single gene locus through the process of alternative splicing (AS). We propose a computational approach called UNCOVER based on a pair hidden Markov model to discover conserved coding exonic sequences subject to AS that have so far gone undetected. Applying UNCOVER to orthologous introns of known human and mouse genes predicts skipped exons or retained introns present in both species, while discriminating them from conserved noncoding sequences. The accuracy of the model is evaluated on a curated set of genes with known conserved AS events. The prediction of skipped exons in the approximately 1% of the human genome represented by the ENCODE regions leads to more than 50 new exon candidates. Five novel predicted AS exons were validated by RT-PCR and sequencing analysis of 15 introns with strong UNCOVER predictions and lacking EST evidence. These results imply that a considerable number of conserved exonic sequences and associated isoforms are still completely missing from the current annotation of known genes. UNCOVER also identifies a small number of candidates for conserved intron retention.

Journal Article↗

Human IgG1 and IgG3 recognition of Schistosoma mansoni 14kDa fatty acid-binding recombinant protein.

The Schistosoma mansoni gene coding for a 14-kDa fatty acid-binding protein was amplified by PCR and subcloned into the prokaryotic expression vector pMAL-c2. Escherichia coli DH5alpha was transformed with the pMAL-Sm14 construct, and gene expression was induced hr isopropyl-beta-D-thiogalactopyranoside. The resulting recombinant (r) fusion protein was purified by affinity chromatography and confirmed by immunoblot analysis using antimaltose-binding protein or anti-Sm14 antibodies. Additionally, an antibody isotype profile was determined in sera of schistosomiasis patients to rSm14 or soluble adult worm antigen preparation. IgG1 and IgG3 subclass antibodies to rSm14 were predominant in sera of all patients studied whereas low levels of IgM, IgA or IgE were measured. Expression of a S. mansoni gene encoding a vaccine candidate is an important step to better study human immune responses to defined antigens.

Adolescent↗

An RNA polymerase-binding protein that is required for communication between an enhancer and a promoter.

Although bacteriophage T4 late promoters are selectively recognized by Escherichia coli RNA polymerase bearing a single protein encoded by T4 gene 55 (gp55), efficient transcription at these promoters requires enhancement by the three T4 DNA polymerase accessory proteins, bound to distal "mobile enhancer" sites. Two principles are shown to govern this transcriptional enhancement: (i) Promoter recognition and communication between the enhancer and the promoter require separate phage-coded proteins. Only RNA polymerase that has the T4 gene 33 protein (gp33) bound to it is subject to enhancement by the three DNA replication proteins. (ii) Transcriptional enhancement in this prokaryotic system is promoter-specific. Promoter specificity is generated by a direct competition of phage T4 gp33 and gp55 with the E. coli promoter recognition protein, sigma 70, for binding to the E. coli RNA polymerase core. Thus, polymerase that contains sigma 70 is competent to transcribe T4 early and middle genes, but lacks the ability to be enhanced by the DNA replication proteins, while polymerase that contains gp55 and gp33 is capable of enhancement via gp33, but its activity is restricted to T4 late promoters by gp55.

Carrier Proteins↗

A class II gene conversion event defines an antigen-specific Ir gene epitope.

To assess the role of Ia epitopes in conferring specificity for the immune response to nominal antigen, we compared the insulin response of mice with a defined mutation in the I-Ab beta gene, the B6.C-H-2bm12 (bm12), with that of wild-type H-2b C57BL/6 (B6) mice. We report that the bm 12 mutation resulted in a selective alteration of the specificity of insulin recognition, such that bm 12 mice responded upon immunization with sheep but not beef insulin, which differ by only one amino acid at position 9 of the insulin A chain. Thus, the bm12 mutation allows for the definition of the actual nucleotide sequence coding for an Ia epitope that is responsible for controlling the specificity of immune recognition of insulin. Furthermore, we show that the sheep insulin response of H-2k mice is controlled by the E molecule and that sheep insulin can be recognized by primed bm12 and H-2k T cells in the context of either bm12, B10.A, or B10.A(5R) antigen-presenting cells. Our data suggest that the mechanism for the bm12 mutation was the intergenic transfer of a hypervariable region in the first domain that is identical in the I-Abm12 beta, I-Eb beta, and I-Ek beta genes.

Animals↗

Processing the trees and the forest during initial stages of face perception: electrophysiological evidence.

Although configural processing is considered a hallmark of normal face perception in humans, there is ample evidence that processing face components also contributes to face recognition and identification. Indeed, most contemporary models posit a dual-code view in which face identification relies on the analysis of individual face components as well as the spatial relations between them. We explored the interplay between processing face configurations and inner face components by recording the N170, an event-related potential component that manifests early detection of faces. In contrast to a robust N170 effect elicited by line-drawn schematic faces compared to line-drawn schematic objects, no N170 effect was found if a pair of small objects substituted for the eyes in schematic faces. However, if a pair of two miniaturized faces substituted for the eyes, the N170 effect was restored. Additional experiments ruled out an explanation on the basis of miniaturized faces attracting attention independent of their location in a face-like configuration and show that global and local face characteristics compete for processing resources when in conflict. The results are discussed as they relate to normal and abnormal face processing.

Adolescent↗

A unified account of the effects of distinctiveness, inversion, and race in face recognition.

A framework is outlined in which individual faces are assumed to be encoded as a point in a multidimensional space, defined by dimensions that serve to discriminate faces. It is proposed that such a framework can account for the effects of distinctiveness, inversion, and race on recognition of faces. Two specific models within this framework are identified: a norm-based coding model, in which faces are encoded as vectors from a population norm or prototype, and a purely exemplar-based model. Both models make similar predictions, albeit in different ways, concerning the interactions between the effects of distinctiveness, inversion and race. These predictions were supported in five experiments in which photographs of faces served as stimuli. The norm-based coding version and the exemplar-based version of the framework cannot be distinguished on the basis of the experiments reported, but it is argued that a multidimensional space provides a useful heuristic framework to investigate recognition of faces. Finally, the relationship between the specific models is considered and an implementation in terms of parallel distributed processing is briefly discussed.

Adult↗

Combining voice recognition and automatic indexing of medical reports.

Medical records have been evolving from the traditional paper-based records to digital ones, from the method of dictating reports and transcription to voice recognition systems. The transition to digital operations will not be complete until we have the ability to combine voice recognition with automated indexing of texts. This paper introduces the methods we used to evaluate existing voice recognition software programs and presents NOMINDEX, a system that turns a medical text into MeSH codes, using the French ADM lexical database. Those systems were applied to 28 patient discharge summaries in French, produced after a coronarography, and extracted from the MENELAS corpus of texts. Using the best configuration for voice recognition, the rate of accurate recognition exceeds 98 percent. Among the indexing concepts assigned by NOMINDEX, 25 percent were not pertinent and 12 percent of the relevant concepts were missing. Most errors were related to confusion between common language and medical language, and to the coverage of the ADM lexical database. Best results would be expected with a more comprehensive lexical resource In addition, only 3 percent of the errors generated by inadequate voice recognition that remained in the configuration that performed better, impacted on automatic indexing by NOMINDEX.

Abstracting and Indexing↗