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An algebraic model of an associative noise-like coding memory.

A mathematical model of an associative memory is presented, sharing with the optical holography memory systems the properties which establish an analogy with biological memory. This memory system--developed from Gabor's model of memory--is based on a noise-like coding of the information by which it realizes a distributed, damage-tolerant, "equipotential" storage through simultaneous state changes of discrete substratum elements. Each two associated items being stored are coded by each other by means of two noise-like patterns obtained from them through a randomizing preprocessing. The algebraic transformations operating the information storage and retrieval are matrix-vector products involving Toeplitz type matrices. Several noise-like coded memory traces are superimposed on a common substratum without crosstalk interference; moreover, extraneous noise added to these memory traces does not injure the stored information. The main performances shown by this memory model are: i) the selective, complete recovering of stored information from incomplete keys, both mixed with extraneous information and translated from the position learnt; ii) a dynamic recollection where the information just recovered acts as a new key for a sequential retrieval process; iii) context-dependent responses. The hypothesis that the information is stored in the nervous system through a noise-like coding is suggested. The model has been simulated on a digital computer using bidimensional images.

Computers↗

An investigation into the interaction between ethanol at low doses and the benzodiazepines nitrazepam and temazepam on psychomotor performance in normal subjects.

Ten healthy male volunteers received, in randomized order, temazepam 20 mg, nitrazepam 5 mg or placebo in combination with ethanol 0.1, 0.2 or 0.4 g/kg. Psychomotor tests were performed at regular intervals over 8 h. Ethanol alone at 0.4 g/kg significantly showed simple reaction time for between 30 and 60 min, whereas nitrazepam (5 mg) or temazepam (20 mg) plus the placebo alcohol dose (0.1 g/g) had no significant effect. The benzodiazepines and ethanol (0.2 and 0.4 g/kg) in combination showed no potentiation or prolongation of action. Both ethanol and the two benzodiazepines significantly reduced critical flicker detection in themselves and, in combination, had additive effects. Only nitrazepam and temazepam produced decreases in performance in the code substitution (DSST) test, and the time course of action of nitrazepam was markedly longer than that of temazepam. Ethanol alone had no detectable effect on immediate recall, prompted recall, learning, or word recognition tests. Both benzodiazepines reduced immediate and prompted recall and nitrazepam, in addition, reduced word recognition ability. It is concluded that the spectrum of CNS depressant actions of ethanol and the benzodiazepines are different and that there is no evidence of a potentiation or prolongation of their effects by concomitant administration of the doses used in the present study.

Adolescent↗

Biased distribution of single nucleotide polymorphisms (SNPs) in porcine Toll-like receptor 1 (TLR1), TLR2, TLR4, TLR5, and TLR6 genes.

Toll-like receptors (TLRs) recognize various microbial components and induce immune responses. Polymorphisms in TLRs may influence their recognition of pathogen-derived molecules; swine TLRs are predicted to be associated with responses to infectious diseases such as pneumonia. In this study, we searched for single nucleotide polymorphisms (SNPs) in the coding sequences of porcine TLR1, TLR2, TLR4, TLR5, and TLR6 genes in 96 pigs from 11 breeds and elucidated 21, 11, 7, 13, and 11 SNPs, respectively, which caused amino acid substitutions in the respective TLRs. Distribution of these nonsynonymous SNPs was biased; many were located in the leucine-rich repeats, particularly in TLR1. These data demonstrated that the heterogeneity of TLR genes was preserved in various porcine breeds despite intensive breeding that was carried out for livestock improvement. It suggests that the heterogeneity in TLR genes is advantageous in increasing the possibility of survival in porcine populations.

Animals↗

Actions blind to conceptually overlapping stimuli.

Participants are worse at identifying spatial symbols (arrowheads) while performing spatially compatible manual key presses. The present experiments investigated the generality of this "blindness effect" to response-compatible stimuli. In Experiment 1 a left key press deteriorated the identification of left-pointing arrows, and a right key press deteriorated the perception of right-pointing arrows, independent of the hands used to press the key. Thus the blindness effect is based on codes of the distal response location rather than on the body-intrinsic anatomical connection of the hands. Experiment 2 extended the blindness effect to verbal responses and written position words (left, right, up, down). Vocalizing a position word blinded to directly compatible position words (e.g., left-left), but not to orthogonally compatible position words (e.g., left-down). This result suggests that the use of identical stimulus-response codes, and not the use of saliency-matching but distinct codes, suffices to produce blindness effects. Finally, Experiment 3 extended the blindness phenomenon beyond the spatial domain by demonstrating blindness between saying color words and perceiving color patches. Altogether, the experiments revealed action-induced blindness to be a phenomenon of broad empirical validity occurring whenever action and perception afford simultaneous access to the same conceptual codes.

Adolescent↗

Organization and expression of genes in the genomic region surrounding the glutamine synthetase gene Gln1 from Lotus japonicus.

The diploid Lotus japonicus was previously suggested as a model for the legume plant family. We present here the nucleotide sequence and the derived gene organization of a small part of the genome in this model plant. Two functional genes with the same transcriptional orientation were identified within the 23326-bp genomic region analysed. The LjGln1 gene encodes a cytosolic glutamine synthetase and the LjKrm (Kinesin repeat motif) gene encodes a polypeptide with similarity to a repeated motif present in the microtubule-associated kinesin light chain protein. Transcripts of the glutamine synthetase gene are found primarily in roots and root nodules, while transcripts of the Krm gene are found in roots, root nodules and leaves. In the region between Gln1 and Krm, the presence of a third gene, Pge1, was suggested by analysis with the Grail exon recognition program. Upstream of the Gln1 gene a segment carrying two apparently non-functional, fragmented copia-like retroelements, dRtp1 and dRtp2, was identified. Sequence similarity to reverse transcriptase- and RNaseH-coding regions defined the defective retro-elements dRtp1 and dRtp2 within this segment. Terminal repeats were not found but three different sets of short direct repeats are located adjacent to the dRtp1 element. The three genes and the incomplete retroelements occupy most of the analysed DNA, leaving approximately one-fifth of the chromosome fragment without recognisable genome constituents.

Amino Acid Sequence↗

Differential effect of adenovirus 2 E3/19K glycoprotein on the expression of H-2Kb and H-2Db class I antigens and H-2Kb- and H-2Db-restricted SV40-specific CTL-mediated lysis.

The E3/19-kDa glycoprotein (E3/19K) coded by adenovirus type 2 (Ad2) is known to inhibit the cell-surface expression of major histocompatibility complex (MHC) class I antigens by binding to the MHC antigens intracellularly, and thus reduces recognition of antigens by MHC-restricted cytotoxic T lymphocytes (CTL). We have studied the effect of the E3/19K expression in SV40-infected monkey cells, TC-7/H-2Kb and TC-7/H-2Db expressing transfected H-2Kb and H-2Db antigens, respectively, on the cell-surface H-2 class I antigens and on lysis of the cells by SV40 large tumor (T)-antigen-specific H-2Kb- and H-2Db-restricted CTL clones. H-2Db antigen expression on TC-7/H-2Db cells was drastically reduced by infection with Ad2 but not with an E3/19K-negative SV40-Ad2 hybrid virus, Ad2+ND1, as early as 12 hr postinfection. However, H-2Kb antigen expression on Ad2-infected TC7/H-2Kb cells remained unaltered, even at 24 hr postinfection. Specific lysis of SV40-infected TC-7/H-2Db cells by H-2Db-restricted SV40 T-antigen-specific CTL clones, Y-1 and Y-3, was strongly reduced by coinfection of the target cells with Ad2 but not with Ad2+ND1. Lysis of SV40-infected TC-7/H-2Kb cells by a H-2Kb-restricted SV40 T-antigen-specific CTL clone Y-4 was also reduced significantly by Ad2 infection, but not Ad2+ND1. These results indicate that the E3/19K protein affects cell-surface expression of H-2Db antigen but not H-2Kb antigen.

Adenovirus E3 Proteins↗

A genetic locus in mutant poliovirus genomes involved in overproduction of RNA polymerase and 3C proteinase.

A mutagenic oligonucleotide cassette was used to introduce single and tandem amino acid substitutions into the proteinase 3C coding region of an infectious poliovirus type 1 cDNA. The sites targeted for mutagenesis, residues 60, 61, and 66, are located within a putative helical loop structure which may be involved in substrate recognition by the enzyme. Fourteen viable 3C proteinase mutants were isolated. A Lys----Arg substitution at position 60 resulted in cold sensitivity for growth at 33 degrees. Replacement of Lys 60 with Ile, either singly or in combination with substitutions at position 61, resulted in viruses that produced three- to fivefold more 3D RNA polymerase than wild-type poliovirus. 3C-mediated processing of the remaining sites within the polyprotein was not noticeably affected. The overproduction of 3D is a consequence of more efficient processing of the carboxy-terminal Gln-Gly amino acid pair of 3C. Together with a previous report in which substitution of Val 54 with an Ala residue results in a poliovirus that produces decreased levels of 3D, these observations provide evidence that the putative loop region (residues 51-66) may be a functional domain involved in recognition of the carboxy-terminal Gln-Gly cleavage site of 3C.

3C Viral Proteases↗

International Commission for Protection against Environmental Mutagens and Carcinogens. ICPEMC Working Paper 5/6. Perspectives in mutation epidemiology, 6. A 1983 view of sentinel phenotypes.

A sentinel phenotype is a clinical disorder or syndrome that (1) occurs sporadically as a consequence of a single, highly penetrant mutant gene, (2) is a dominant or X-linked trait of considerable frequency and low fitness, and (3) is uniformly expressed and accurately diagnosable with minimal effort at or near birth. Although 1828 autosomal dominant traits are known in human beings, 36 can be considered as candidate sentinel phenotypes, along with 5 X-linked disorders. Based on surveys of malformations in infants and children, 16 additional traits are proposed beyond previous lists. In Hungary, the 24 syndromes or defects with reliable manifestations in newborn infants occur with a frequency of 2.5-3.3 per 10 000 live births. As markers of human mutations, sentinel phenotypes have the advantage of representing germinal mutations that result in significant health problems. There are severe disadvantages that have, to date, prevented the launching of a field demonstration of the value of these phenotypes in mutation epidemiology. Agreement on a list of phenotypes has been delayed by continued recognition of two or more distinct genetic diseases within what was once thought to be a single disorder. For the same reason, most of the candidate sentinel phenotypes have not been assigned unique codes in the International Classification of Diseases. Each of the disorders is so rare and has features that overlap with so many other syndromes that highly trained clinical dysmorphologist and pediatric ophthalmologists would have to be engaged in any study. The sentinel phenotype approach, like other strategies in mutation epidemiology, would encounter problems with linkage among files of data, privacy, and access to sufficiently large populations. In contrast with the approach using multiple protein variants (as in the study of blood from offspring of survivors of the atomic bombs in Hiroshima and Nagasaki), the sentinel phenotype approach would likely be much less expensive and would encounter far fewer false attributions of paternity, but also would require a much larger study population. The best option for the present, in our opinion, is to broaden and sustain critical discussion of the approach. Perhaps the goal should be to plan a field demonstration by involving appropriate clinicians, epidemiologists, and public health officials. A pilot effort underway in Hungary may well give insight to applying the approach in a significantly larger population.

Chromosome Aberrations↗

Effect of face familiarity on age decision.

The present experiment was planned to check whether the extraction of apparent age is affected by face identity (familiarity) or not. According to the traditional view, age estimation should be carried out independently of face identity, because it is one of the visually derived semantic codes (like gender and ethnicity). However, little is known about its underlying mechanisms. Moreover, some recent studies have cast doubt on the parallel thesis regarding facial expression, facial speech, ethnicity, and gender. Given the promising results of a pilot experiment (n=24), 16 Caucasian participants were enrolled in an "age decision" task on morphed faces derived from one old and one young source-face, in the proportion 70:30. The respondents had previously been familiarised with half the source faces by a learning procedure (associating the face, surname, occupation and city of residence of the person displayed), while the remaining half were unfamiliar. The results showed that age decision was affected by face familiarity, at least when the task was perceptually difficult enough. This adds support to the thesis that the identification of identity and the extraction of visually derived semantic codes are not made independently from each other. The status of age, within the visually derived semantic codes, is also discussed.

Aging↗

Cloning and characterization of a shrimp clip domain serine protease homolog (c-SPH) as a cell adhesion molecule.

Clip domain serine protease homologs (c-SPHs) are involved in various innate immune functions in arthropods such as antimicrobial activity, cell adhesion, pattern recognition, opsonization, and regulation of the prophenoloxidase system. In the present study, we cloned a c-SPH cDNA from tiger shrimp (Penaeus monodon) hemocytes. It is 1337 bp in length with a coding region of 1068 bp consisting a protein of 355 amino acid residues. The deduced protein includes one clip domain and one catalytically inactive serine protease-like (SP-like) domain. Its molecular weight is estimated to be 38 kDa with an isoelectric point of 7.9. The predicted cutting site of the signal peptide is located between Gly(21) and Gln(22). We aligned 15 single clip domain SPH protein sequences from 12 arthropod species; the identity of these clip domains is low and that of SP-like domains is from 34% to 46%. The conserved regions are located near the amino acid residues which served as substrate interaction sites in catalytically active serine protease. Phylogenetically, the tiger shrimp c-SPH is most similar to a low molecular mass masquerade-like protein of crayfish, but less similar to c-SPHs in Chelicerata and Insecta. Nested reverse transcription polymerase chain reaction (RT-PCR) revealed that c-SPH mRNA is expressed most in tissues with the highest hemocyte abundance. Antimicrobial and opsonization activities of the molecule were not detected. The expression of c-SPH mRNA in hemocytes was up-regulated at the 12-day post beta-glucan immersion. Recombinant c-SPH could significantly enhance hemocyte adhesion. The result suggests that the shrimp c-SPH protein plays a role in innate immunity.

Amino Acid Sequence↗

Masked form priming in writing words from pictures: evidence for direct retrieval of orthographic codes.

Three experiments used the masked priming paradigm to investigate the role of orthographic and phonological information in written picture naming. In all the experiments, participants had to write the names of pictures as quickly as possible under three different priming conditions. Nonword primes could be: (1) phonologically and orthographically related to the picture name; (2) orthographically related as in (1) but phonologically related to a lesser degree than in (1); (3) orthographically and phonologically unrelated except for the first consonant (or consonant cluster). Orthographic priming effects were observed with a prime exposure duration of 34 ms (Experiments 1 and 2) and of 51 ms (Experiment 3). In none of the experiments, did homophony between primes and picture names yield an additional advantage. Taken together, these findings support the view of the direct retrieval of orthographic information through lexical access in written picture naming, and thus argue against the traditional view that the retrieval of orthographic codes of obligatorily mediated by phonology.

Adult↗

The influence of divided attention on holistic face perception.

There is evidence that upright, but not inverted, faces are encoded holistically. The holistic coding of faces was examined in four experiments by manipulating the attention allocated to target faces. In Experiment 1, participants in a divided attention condition were asked to match two upright flanker faces while encoding a centrally presented upright target face. Although holistic coding was evident in the full attention conditions, dividing attention disrupted holistic coding of target faces. In Experiment 2, we found that while matching upright flanker faces disrupted holistic coding, matching inverted flanker faces did not. Experiment 3 demonstrated that the differential effects of flanker orientation were not due to participants taking longer to match upright, than inverted, flanker faces. In Experiment 4, we found that matching fractured faces had an intermediate effect to that of matching upright and inverted flankers, on the holistic coding of the target faces. The findings emphasize the differences in processing of upright, fractured and inverted faces and suggest that there are limitations in the number of faces that can be holistically coded in a brief time.

Adolescent↗

Analysis of the structure-activity relationship of four herpesviral UL97 subfamily protein kinases reveals partial but not full functional conservation.

Herpesviral protein kinases of the UL97 subfamily are expressed by all known herpesviruses but the degree of functional conservation is unclear. A selection of representative members was investigated by a comparative structural and functional analysis. The coding sequences of human cytomegalovirus (HCMV) pUL97, rat CMV pR97, Epstein-Barr virus BGLF4, and herpes simplex virus UL13 showed a low degree of amino acid identity. A computational approach employing fold recognition techniques revealed structural similarity to the cellular kinase Cdk2 with a high level of conservation of the functionally important residues in ATP binding sites and the catalytic centers. Analyses of in vitro activities of these herpesviral protein kinases, including measurements of phosphorylation of cellular substrates, trans-complementation experiments with a UL97-deleted HCMV mutant, and sensitivity profiles toward protein kinase inhibitors, demonstrated marked similarities between pUL97 and pR97 and to a lesser extent between pUL97 and BGLF4 or UL13. Thus, the structure-activity analysis of pUL97-like herpesviral protein kinases indicates a partial but not a full conservation of their functional properties among the herpesviruses.

Adenosine Triphosphate↗

Solution structure of family 21 carbohydrate-binding module from Rhizopus oryzae glucoamylase.

CBMs (carbohydrate-binding modules) function independently to assist carbohydrate-active enzymes. Family 21 CBMs contain approx. 100 amino acid residues, and some members have starchbinding functions or glycogen-binding activities. We report here the first structure of a family 21 CBM from the SBD (starch-binding domain) of Rhizopus oryzae glucoamylase (RoCBM21) determined by NMR spectroscopy. This CBM has a beta-sandwich fold with an immunoglobulin-like structure. Ligand-binding properties of RoCBM21 were analysed by chemical-shift perturbations and automated docking. Structural comparisons with previously reported SBDs revealed two types of topologies, namely type I and type II, with CBM20, CBM25, CBM26 and CBM41 showing type I topology, with CBM21 and CBM34 showing type II topology. According to the chemical-shift perturbations, RoCBM21 contains two ligand-binding sites. Residues in site II are similar to those found in the family 20 CBM from Aspergillus niger glucoamylase (AnCBM20). Site I, however, is embedded in a region with unique sequence motifs only found in some members of CBM21s. Additionally, docking of beta-cyclodextrin and malto-oligosaccharides highlights that side chains of Y83 and W47 (one-letter amino acid code) form the central part of the conserved binding platform in the SBD. The structure of RoCBM21 provides the first direct evidence of the structural features and the basis for protein-carbohydrate recognition from an SBD of CBM21.

Binding Sites↗

Initiator tRNA may recognize more than the initiation codon in mRNA: a model for translational initiation.

A special methionine tRNA (tRNAi) is universally required to initiate translation. Amongst species a tRNAi structural conservation is most apparent in the anticodon and T arms of the molecule but extends into the variable loop and the 3' strand of the D stem. This suggested that they could share a similar ancestral or current function in initiation of translation. We report that the sequence of bases neighboring the translational start codons of many eubacterial genes are complementary not only to the extended anticodon but also to the D and T loops of tRNAi. Study of the coding properties of tRNAi and of mutations that affect translation suggests that the translational start domain can be a mosaic of signals complementary to the loops of tRNAi. The hypothesis of multiple loop recognition suggests that unusual triplets can start prokaryotic and mitochondrial genes and predicts the occurrence of other reading frames. Furthermore, it suggests a unifying model for chain initiation based on RNA contacts and displacements.

Animals↗

RNA-binding proteins that specifically recognize the selenocysteine insertion sequence of human cellular glutathione peroxidase mRNA.

Translational incorporation of the unusual amino acid selenocysteine in eukaryotes requires a coding region UGA codon (which otherwise serves as a termination signal), a selenocysteine insertion sequence (SECIS) in the 3'-untranslated region of the mRNA, and selenocysteyl-tRNA. The mechanisms involved in SECIS recognition by the eukaryotic translational machinery remain unknown. We report the detection of RNA-binding proteins that specifically recognize the SECIS from human cellular glutathione peroxidase (GPX1) transcripts. RNA gel shift assays showed three retarded bands after incubation with COS-1 whole cell lysate or S-100 cytosol fraction or with extracts from hepatoma cell lines HepG2 and Hep3B. The specificity of the binding was demonstrated by competition by cold unlabeled SECIS RNA and by lack of competition by other RNA species with similar stem-loop secondary structures, such as the human immunodeficiency virus (HIV) transactivation-response region of HIV mRNA element, and mutated SECIS constructs. UV cross-linking and SDS-polyacrylamide gel electrophoresis revealed at least two proteins, with estimated molecular masses of 55,000 and 65,000 Da, that bind to the SECIS. Examination of a series of insertion and deletion SECIS mutants indicated recognition of the SECIS primarily through the basal stem region, although the upper stem, loop, and two of three short conserved sequences also appear to contribute to the affinity of the binding.

Base Sequence↗

Patterns of codon recognition by isoacceptor aminoacyl-tRNAs from wheat germ.

Isoacceptors of Ala-, Arg-, Glu-, Gln-, Ile-, Leu-, Lys-, Ser-, Thr- and Val-tRNAs from wheat germ have been resolved by reverse phast chromatography. Codon recognition properties have been determined on isolated fractions of each of these aa-tRNAs and codon assignments have been made to a number of isoacceptors. Evolutionary changes which have occurred in patterns of codon recognition by isoacceptor aa-tRNAs in wheat germ and other organisms are discussed.

Biological Evolution↗

Acoustic parameters measured by a formant-estimating speech processor for a multiple-channel cochlear implant.

In order to assess the limitations imposed on a cochlear implant system by a wearable speech processor, the parameters extracted from a set of 11 vowels and 24 consonants were examined. An estimate of the fundamental frequency EF 0 was derived from the zero crossings of the low-pass filtered envelope of the waveform. Estimates of the first and second formant frequencies EF 1 and EF 2 were derived from the zero crossings of the waveform, which was filtered in the ranges 300-1000 and 800-4000 Hz. Estimates of the formant amplitudes EA 1 and EA 2 were derived by peak detectors operating on the outputs of the same filters. For vowels, these parameters corresponded well to the first and second formants and gave sufficient information to identify each vowel. For consonants, the relative levels and onset times of EA 1 and EA 2 and the EF 0 values gave cues to voicing. The variation in time of EA 1, EA 2, EF 1, and EF 2 gave cues to the manner of articulation. Cues to the place of articulation were given by EF 1 and EF 2. When pink noise was added, the parameters were gradually degraded as the signal-to-noise ratio decreased. Consonants were affected more than vowels, and EF 2 was affected more than EF 1. Results for three good patients using a speech processor that coded EF 0 as an electric pulse rate, EF 1 and EF 2 as electrode positions, and EA 1 and EA 2 as electric current levels confirmed that the parameters were useful for recognition of vowels and consonants. Average scores were 76% for recognition of 11 vowels and 71% for 12 consonants in the hearing-alone condition. The error rates were 4% for voicing, 12% for manner, and 25% for place.

Cochlear Implants↗