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PubMed1994

Transmembrane signalling by a hybrid protein: communication from the domain of chemoreceptor Trg that recognizes sugar-binding proteins to the kinase/phosphatase domain of osmosensor EnvZ.

Chemoreceptor Trg and osmosensor EnvZ of Escherichia coli share a common transmembrane organization but have essentially unrelated primary structures. We created a hybrid gene coding for a protein in which Trg contributed its periplasmic and transmembrane domains as well as a short cytoplasmic segment and EnvZ contributed its cytoplasmic kinase/phosphatase domain. Trz1 transduced recognition of sugar-occupied, ribose-binding protein by its periplasmic domain into activation of its cytoplasmic kinase/phosphatase domain as assessed in vivo by using an ompC-lacZ fusion gene. Functional coupling of sugar-binding protein recognition to kinase/phosphatase activity indicates shared features of intramolecular signalling in the two parent proteins. In combination with previous documentation of transduction of aspartate recognition by an analogous fusion protein created from chemoreceptor Tar and EnvZ, the data indicate a common mechanism of transmembrane signal transduction by chemoreceptors and EnvZ. Signalling through the fusion proteins implies functional interaction between heterologous domains, but the minimal sequence identity among relevant segments of EnvZ, Tar, and Trg indicates that the link does not require extensive, specific interactions among side chains. The few positions of identity in those three sequences cluster in transmembrane segment 1 and the short chemoreceptor sequence in the cytoplasmic part of the hybrid proteins. These regions may be particularly important in physical and functional coupling. The specific cellular conditions necessary to observe ligand-dependent activation of Trz1 can be understood in the context of the importance of phosphatase control in EnvZ signalling and limitations on maximal receptor occupancy in binding protein-mediated recognition.

Amino Acid Sequence↗

PubMed1988

Molecular comparisons of in vivo- and in vitro-derived strains of Aleutian disease of mink parvovirus.

DNA from one cell culture-adapted and two pathogenic strains of Aleutian disease of mink parvovirus (ADV) was molecularly cloned into the vectors pUC18 and pUC19. The DNA from the two pathogenic strains (ADV-Utah I and ADV-Pullman) was obtained from virus purified directly from the organs of infected mink, whereas the DNA from the nonpathogenic ADV-G was derived from cell culture material. The cloned segment from all three viruses represented a 3.55-kilobase-pair BamHI (15 map units) to HindIII (88 map units) fragment. Detailed physical mapping studies indicated that all three viruses shared 29 of 46 restriction endonuclease recognition sites but that 6 sites unique to the pathogenic strains and 5 sites unique to ADV-G were clustered in the portion of the genome expected to code for structural proteins. Clones from all three viruses directed the synthesis of two ADV-specific polypeptides with molecular weights of approximately 57 and 34 kilodaltons. Both species reacted with sera from infected mink as well as with a monoclonal antibody specific for ADV structural proteins. Because production of these ADV antigens was detected in both pUC18 and pUC19 and was not influenced by isopropyl-beta-D-thiogalactopyranoside (IPTG) induction, their expression was not regulated by the lac promoter of the pUC vector, but presumably by promoterlike sequences found within the ADV DNA. The proteins specified by the clones of ADV-G were 2 to 3 kilodaltons smaller than those of the two pathogenic strains, although the DNA segments were identical in size. This difference in protein molecular weights may correlate with pathogenicity, because capsid proteins of pathogenic and nonpathogenic strains of ADV exhibit a similar difference.

Aleutian Mink Disease Virus↗

PubMed2006

Microbial nucleic acids pay a Toll in kidney disease.

Nucleic acids provide more than the genetic code that determines the morphological and functional phenotype of microbes and eukaryotes. In fact, nucleic acids have immunomodulatory functions as they are recognized by a set of pattern-recognition receptors that initiate and modulate immune responses in the host. Toll-like receptor (TLR)-3 recognizes double-stranded RNA, TLR7 and TLR8 recognize single-stranded RNA, CpG-DNA is a ligand for TLR9, and all of these TLRs are expressed in the nephritic kidney. In this review, we summarize recent advances in this field and discuss new hypotheses for the pathogenesis of kidney diseases that are triggered by infectious organisms.

Animals↗

PubMed1999

Feature extraction through LOCOCODE.

Low-complexity coding and decoding (LOCOCODE) is a novel approach to sensory coding and unsupervised learning. Unlike previous methods, it explicitly takes into account the information-theoretic complexity of the code generator. It computes lococodes that convey information about the input data and can be computed and decoded by low-complexity mappings. We implement LOCOCODE by training autoassociators with flat minimum search, a recent, general method for discovering low-complexity neural nets. It turns out that this approach can unmix an unknown number of independent data sources by extracting a minimal number of low-complexity features necessary for representing the data. Experiments show that unlike codes obtained with standard autoencoders, lococodes are based on feature detectors, never unstructured, usually sparse, and sometimes factorial or local (depending on statistical properties of the data). Although LOCOCODE is not explicitly designed to enforce sparse or factorial codes, it extracts optimal codes for difficult versions of the "bars" benchmark problem, whereas independent component analysis (ICA) and principal component analysis (PCA) do not. It produces familiar, biologically plausible feature detectors when applied to real-world images and codes with fewer bits per pixel than ICA and PCA. Unlike ICA, it does not need to know the number of independent sources. As a preprocessor for a vowel recognition benchmark problem, it sets the stage for excellent classification performance. Our results reveal an interesting, previously ignored connection between two important fields: regularizer research and ICA-related research. They may represent a first step toward unification of regularization and unsupervised learning.

Algorithms↗

PubMed1982

Children's categorical representation of oblique orientation.

20 7-yr.-old children were given a memory task in which they were asked to compare successively presented oblique lines. The lines varied in respect to (1) their position within a square display and (2) their relation to the diagonal axis of the display. Children's performance suggests a categorical spatial representation system in which stimuli are encoded in terms of position and axis features. In comparing the orientation of two oblique lines, children match these coded categorical features (e.g., on axis vs off axis) and respond by the simple response rule: if a match say "same," if a mismatch say "different," so, children's recognition of oblique lines is often in error.

Child↗

PubMed1996

[Effects of subjective-familiarity vs. unfamiliarity of faces on face recognition in preschool children].

The purpose of this study was to investigate the effects of subjective-familiarity vs. unfamiliarity and the age of faces (adult faces vs. child faces) on immediate and delayed face recognition in preschool children. Subjective-familiarity is a feeling that one takes unfamiliar faces as resembling actual familiar ones. Fifty-six preschool children were given instructions which made them focus on either Subjectively Familiar Face (SFF) or Unfamiliar Face (UF), and No-Instruction (NI) condition was set as a control. In the SFF condition the subjects were required to judge whether the faces resembled someone they knew; in the UF condition they were required to pick out faces new to them. The major findings were that the SFF instruction facilitated recognition scores (d') and this tendency was especially strong in the delayed test. These results were interpreted as showing that the SFF instruction enhanced information processing at the constructional coding level. One of the reasons why preschool children are deficient in recognizing unfamiliar faces is that they have not yet developed the ability to process information at the constructional coding level.

Adult↗

PubMed1975

[Physiologic mechanisms of the constancy of color perception].

The color constancy is the ability to recognize correctly the colours of the objects under different illuminations. For this purpose the visual system must identify the character of illumination and estimate the colour of the object, using the light reflected from this object according to the spectrum of illumination. The behavioral experiments with fishes showed that they possess the colour constancy. The electrophysiological studies on colour-coding ganglion cells showed that the simplest mechanisms of estimating the colours of objects according to illumination exist at the retinal level. The presence of colour vision facilitates the recognition of the volume form of the objects. The generally accepted view on the place and role of colour vision in the general function of the visual system of animals has to be changed on the basis of these facts.

Animals↗

PubMed1996

History of the Medical Library Association's credentialing program.

Since the Medical Library Association (MLA) adopted the Code for the Training and Certification of Medical Librarians in 1949, MLA members have reviewed and revised the program regularly. This paper traces the history of MLA's professional recognition program to illustrate how the program has changed over time and to identify the issues that have surrounded it. These issues include the value of the program to individual members, cost to MLA, appropriate entry requirements, certification examinations, and recertification requirements. The development and operation of MLA's current credentialing program, the Academy of Health Information Professionals, is described in detail.

Academies and Institutes↗

PubMed2025

Missense variants in human forkhead transcription factors reveal determinants of forkhead DNA bispecificity.

Recognition of specific DNA sequences by transcription factors (TFs) is a key step in transcriptional control of gene expression. While most forkhead (FH) TFs bind either an FKH (RYAAAYA) or an FHL (GACGC) recognition motif, some FHs can bind both motifs. Mechanisms that control whether an FH is monospecific vs. bispecific have remained unknown. Screening a library of 12 reference FH proteins, 61 naturally occurring missense variants including clinical variants, and 22 designed mutant FHs for DNA-binding activity using universal ("all 10-mer") protein-binding microarrays revealed non-DNA-contacting residues that control mono- vs. bispecificity. Variation in non-DNA-contacting amino acid residues of TFs is associated with human traits and may play a role in the evolution of TF DNA-binding activities and gene regulatory networks.

Humans↗

PubMed1999

JPEG quality transcoding using neural networks trained with a perceptual error measure.

A JPEG Quality Transcoder (JQT) converts a JPEG image file that was encoded with low image quality to a larger JPEG image file with reduced visual artifacts, without access to the original uncompressed image. In this article, we describe technology for JQT design that takes a pattern recognition approach to the problem, using a database of images to train statistical models of the artifacts introduced through JPEG compression. In the training procedure for these models, we use a model of human visual perception as an error measure. Our current prototype system removes 32.2% of the artifacts introduced by moderate compression, as measured on an independent test database of linearly coded images using a perceptual error metric. This improvement results in an average PSNR reduction of 0.634 dB.

Algorithms↗

PubMed1990

Recognition of egocentric and allocentric visual and auditory space by neurons in the hippocampus of monkeys.

Neuronal activity in the hippocampus was recorded in the awake monkey during presentation of visual and auditory stimuli from various directions. About 10% of the neurons coded visual and/or auditory information from unique directions. Some of these neurons were stimulus-selective, and others were not. Three types of neurons were identified by rotating the animals: egocentric and allocentric, and indeterminate. The results are consistent with a role of the hippocampus in spatial memory.

Acoustic Stimulation↗

PubMed2006

An iterative refinement algorithm for consistency based multiple structural alignment methods.

MOTIVATION: Multiple STructural Alignment (MSTA) provides valuable information for solving problems such as fold recognition. The consistency-based approach tries to find conflict-free subsets of alignments from a pre-computed all-to-all Pairwise Alignment Library (PAL). If large proportions of conflicts exist in the library, consistency can be hard to get. On the other hand, multiple structural superposition has been used in many MSTA methods to refine alignments. However, multiple structural superposition is dependent on alignments, and a superposition generated based on erroneous alignments is not guaranteed to be the optimal superposition. Correcting errors after making errors is not as good as avoiding errors from the beginning. Hence it is important to refine the pairwise library to reduce the number of conflicts before any consistency-based assembly. RESULTS: We present an algorithm, Iterative Refinement of Induced Structural alignment (IRIS), to refine the PAL. A new measurement for the consistency of a library is also proposed. Experiments show that our algorithm can greatly improve T-COFFEE performance for less consistent pairwise alignment libraries. The final multiple alignment outperforms most state-of-the-art MSTA algorithms at assembling 15 transglycosidases. Results on three other benchmarks showed that the algorithm consistently improves multiple alignment performance. AVAILABILITY: The C++ code of the algorithm is available upon request.

Algorithms↗

PubMed1997

Substrate recognition domains as revealed by active hybrids between the D-arabinitol and ribitol transporters from Klebsiella pneumoniae.

Two new genes, dalT and rbtT, have been cloned from the dal operon for D-arabinitol and the rbt operon for ribitol uptake and degradation, respectively, in Klebsiella pneumoniae 1033-5P14, derivative KAY2026. Each gene codes for a specific transporter which, based on sequence data, belongs to a large family of carbohydrate transporters which constitutes 12 transmembrane helices. DalT and RbtT show an unusually high similarity (86.2% identical residues for totals of 425 and 427 amino acids, respectively). This allowed the construction of DalT'-Rbt"T and RbtT'-Dal'T crossover hybrids by using a natural restriction site overlapping Met202. This site is located within the large cytoplasmic loop which connects the putative helices 6 and 7 and in particular the amino- and the carboxy-terminal halves of the transporters. Both hybrids have close to normal transport activities but essentially the substrate specificities and kinetic properties of the amino-terminal half. This result localizes essential substrate binding and recognition sites to the amino-terminal halves of the proteins in this important class of carbohydrate transporters.

Amino Acid Sequence↗

PubMed1994

Inhibition of human IgE synthesis by anti-IgE antibodies requires divalent recognition.

We used a selection of well-characterized murine monoclonal anti-IgE antibodies to investigate their effect on human in vitro IgE synthesis. We found anti-IgE antibodies that either inhibited or enhanced interleukin-4 plus anti-CD40-induced in vitro IgE synthesis in peripheral blood mononuclear cells (PBMC). This differential activity was isotype specific as neither IgM nor IgG synthesis were affected. Interestingly, only coding IgE mRNA was down-regulated, whereas germ-line epsilon RNA expression was not influenced by anti-IgE monoclonal antibody (mAb). On purified B cells all anti-IgE mAb inhibited interleukin-4 plus anti-CD40-induced IgE synthesis, implying a role of non-B cells for the enhancing activity observed in PBMC. Using Fab and F(ab')2 of an inhibitory anti-IgE mAb we could show that divalent recognition was required for inhibition of IgE synthesis.

Antibodies, Anti-Idiotypic↗

PubMed2002

Searching for RNA genes using base-composition statistics.

The hypothesis that genomic regions rich in non-protein-coding RNAs (ncRNAs) can be identified using local variations in single-base and dinucleotide statistics has been investigated. (G+C)%, (G-C)% difference, (A-T)% difference and dinucleotide-frequency statistics were compared among seven classes of ncRNAs and three genomes. Significant variations were observed in (G+C)% and, in Methanococcus jannaschii, in the frequency of the dinucleotide 'CG'. Screening programs based on these two base-composition statistics were developed. With (G+C)% screening alone, a 1% fraction of the M.jannaschii genome containing all 44 known transfer RNAs, ribosomal RNAs and signal recognition particle RNAs could be identified. When (G+C)% combined with CG dinucleotide-frequency screening was used, 43 of the 44 known M.jannaschii structural ncRNAs were again identified, while the number of presumably false hits overlapping a known or putative protein-coding gene was reduced from 15 to 6. In addition, 19 candidate ncRNAs were identified including one with significant homology to several known archaeal RNaseP RNAs.

Animals↗

PubMed1991

Resonant recognition model and protein topography. Model studies with myoglobin, hemoglobin and lysozyme.

This study describes the further extension of the resonant recognition model for the analysis and prediction of protein--protein and protein--DNA structure/function dependencies. The model is based on the significant correlation between spectra of numerical presentations of the amino acid or nucleotide sequences of proteins and their coded biological activity. According to this physico-mathematical method, it is possible to define amino acids in the sequence which are predicted to be the most critical for protein function. Using sperm whale myoglobin, human hemoglobin and hen egg white lysozyme as model protein examples, sets of predicted amino acids, or so-called 'hot spots', have been identified within the tertiary structure. It was found for each protein that the predicted 'hot spots', which are distributed along the primary sequence, are spatially grouped in a dome-like arrangement over the active site. The identified amino acids did not correspond to the amino acid residues which are involved in the chemical reaction site of these proteins. It is thus proposed that the resonant recognition model helps to identify amino acid residues which are important for the creation of the molecular structure around the catalytic active site and also the associated physical field conditions required for biorecognition, docking of the specific substrate and full biological activity.

Animals↗

PubMed1999

Signal joint formation is inhibited in murine scid preB cells and fibroblasts in substrates with homopolymeric coding ends.

During B and T lymphocyte development, immunoglobulin and T cell receptor genes are assembled from the germline V, (D) and J gene segments (Lewis, S.M., 1994. The mechanism of V(D)J joining: lessons from molecular, immunological and comparative analyses. Adv. Immunol. 56, 27-150). These DNA rearrangements, responsible for immune system diversity, are mediated by a site specific recombination machinery via recognition signal sequences (RSSs) composed of conserved heptamers and nonamers separated by spacers of 12 or 23 nucleotides (Lewis, S.M., 1994. The mechanism of V(D)J joining: lessons from molecular, immunological and comparative analyses. Adv. Immunol. 56, 27-150). Recombination occurs only between a RSS with a 12mer spacer and a RSS with a 23mer spacer (Lewis, S.M., 1994. The mechanism of V(D)J joining: lessons from molecular, immunological and comparative analyses. Adv. Immunol. 56, 27-150). RAG1 and RAG2 proteins cleave precisely at the RSS-coding sequence border leading to flush signal ends and coding ends with a hairpin structure (Eastman, M., Leu, T., Schatz, D., 1996. Initiation of V(D)J recombination in vitro obeying the 12/23 rule. Nature 380, 85-88; Roth, D.B., Menetski, J.P., Nakajima, P.B., Bosma, M.J., Gellert, M., 1992. V(D)J recombination: broken DNA molecules with covalently sealed (hairpin) coding ends in scid mouse thymocytes. Cell 983-991: Roth, D.B., Zhu, C., Gellert. M., 1993. Characterization of broken DNA molecules associated with V(D)J recombination. Proc. Natl. Acad. Sci. USA 90, 10,788-10,792; van Gent, D., McBlane, J.. Sadofsky, M., Hesse, J., Gellert, M., 1995. Initiation of V(D)J recombination in a cell-free system. Cell 81, 925-934). Signal ends join, forming a signal joint. The hairpin coding ends are opened by a yet unknown endonuclease, and are further processed to form the coding joint (Lewis, S.M., 1994. The mechanism of V(D)J joining: lessons from molecular, immunological and comparative analyses. Ad. Immunol. 56, 27-150.) The murine scid mutation has been shown to affect coding joints, but much less signal joint formation. In this study we demonstrate that the murine scid mutation inhibits correct signal joint formation when both coding ends contain homopolymeric sequences. We suggest that this finding may be due to the function of the SCID protein as an assembly component in V(D)J recombination.

Animals↗

PubMed1987

The alpha 1 and alpha 2 domains of H-2 class I molecules interact to form unique epitopes.

Mouse class I antigens are the major targets of cytolytic T lymphocytes in both major histocompatibility complex (MHC)-restricted and allogeneic responses. Considerable evidence has recently accumulated demonstrating that MHC class I molecules encoded by genes whose alpha 1 and alpha 2 coding exons were interchanged are not recognized by T lymphocytes specific for parental class I products. Along with the loss of T-cell reactivity, there is a loss of recognition by some, but not all monoclonal antibodies. In this communication we report that the loss of reactivity by monoclonal antibodies is accompanied by the gain of new epitopes caused by the interaction of alpha 1 and alpha 2 domains. These epitopes are immunodominant. They are the major determinant recognized by polyclonal antisera raised by immunization with L cells transfected with exon-shuffled class I genes. Four new monoclonal antibodies have been produced which recognize at least two separate epitopes caused by the interaction of the alpha 1p and alpha 2d domains.

Animals↗