PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Receptors, Pattern Recognition”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 901 records · Page 50Linked to original sources
PubMed2003

Single-nucleotide polymorphisms in the Toll-like receptor 9 gene (TLR9): frequencies, pairwise linkage disequilibrium, and haplotypes in three U.S. ethnic groups and exploratory case-control disease association studies.

TLR9 is a mammalian Toll-like receptor homologue that appears to function as an innate immune pattern recognition protein for motifs that are far more common in bacterial than in mammalian DNA. The gene was sequenced in 71 subjects from three self-identified U.S. ethnic groups to identify single-nucleotide polymorphisms (SNPs). A total of 20 SNPs were found of which only 20% were in the public dbSNP database. Four SNPs were relatively common in all three ethnic samples. Using these four SNPs, seven distinct haplotypes were statistically inferred, of which four accounted for 75% or more chromosomes. These four haplotypes could be distinguished from each other by the alleles of two SNPs (-1237 and 2848). Five exploratory nested case-control disease-association studies (asthma, DVT, MI, and COPD in European Americans and asthma in African Americans) were performed by genotyping DNA collected from four ongoing cohort studies. There was evidence suggesting increased risk for asthma with a C allele at -1237 (odds ratio 1.85, 95%CI 1.05 to 3.25) among European Americans (genotypes available from 67 cases and 152 controls). No other significant disease associations were detected. Replication of this finding in other, larger samples is needed. This study suggests that there is substantial diversity in human TLR9, possibly associated with asthma in Europeans but not African Americans. No association was detected with three other diseases potentially related to innate immunity.

Black People↗
PubMed2005

Pre- or post-training administration of the NMDA receptor blocker MK-801 impairs object recognition memory in rats.

The aim of the present study was to investigate the effects of NMDA receptor blockade on formation of object recognition memory. In the first experiment, adult Wistar rats were given an intraperitoneal injection of saline or the NMDA receptor antagonist [(+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclo-hepten-5,10-imine-maleate] (MK-801) (0.001, 0.01, or 0.1 mg/kg) 20 min prior to training in a novel object recognition task. In the second experiment, saline or MK-801 (0.1 mg/kg) were given immediately after training. Memory retention was tested 1.5 and 24 h after training. MK-801 impaired both short- and long-term retention of object recognition memory when given either before or after training. The results suggest that NMDA receptor activation is necessary for formation of object recognition memory.

Animals↗
PubMed2005

Specificity of the effect of a nicotinic receptor polymorphism on individual differences in visuospatial attention.

Cortical neurotransmitter availability is known to exert domain-specific effects on cognitive performance. Hence, normal variation in genes with a role in neurotransmission may also have specific effects on cognition. We tested this hypothesis by examining associations between polymorphisms in genes affecting cholinergic and noradrenergic neurotransmission and individual differences in visuospatial attention. Healthy individuals were administered a cued visual search task which varied the size of precues to the location of a target letter embedded in a 15-letter array. Cues encompassed 1, 3, 9, or 15 letters. Search speed increased linearly with precue size, indicative of a spatial attentional scaling mechanism. The strength of attentional scaling increased progressively with the number of C alleles (0, 1, or 2) of the alpha-4 nicotinic receptor gene C1545T polymorphism (n = 104). No association was found for the dopamine beta hydroxylase gene G444A polymorphism (n = 135). These findings point to the specificity of genetic neuromodulation. Whereas variation in a gene linked to cholinergic transmission systematically modulated the ability to scale the focus of visuospatial attention, variation in a gene governing dopamine availability did not. The results show that normal variation in a gene controlling a nicotinic receptor makes a selective contribution to individual differences in visuospatial attention.

Adult↗
PubMed2005

Bovine toll-like receptor 9: a comparative analysis of molecular structure, function and expression.

Non-methylated CpG motifs, present in viral and bacterial DNA, are one of many pathogen-associated molecular patterns (PAMP) recognized by the mammalian innate immune system. Recognition of this PAMP occurs through a specific interaction with toll-like receptor 9 (TLR9) and this interaction can induce cytokine responses that influence both innate and adaptive immune responses. Previous investigations determined that both the flanking sequences in synthetic CpG oligodeoxynucleotides (CpG ODN) and the cellular pattern of TLR9 expression can influence species-specific responses to CpG ODN. Therefore, the structure, function and cellular distribution of bovine TLR9 were compared with what is known for mice and human. Analysis of the bovine TLR9 gene revealed greater sequence homology between cattle and humans than cattle and mice Similar CpG motifs induced optimal activation of both human and bovine leukocytes and these motifs were distinct from those which activated mouse leukocytes. Functional analyses with CpG ODN stimulated bovine blood leukocytes revealed that class A CpG ODN were more potent inducers of interferon-alpha (IFN-alpha) than class B CpG ODN. Furthermore, magnetic activated cell sorting of bovine blood leukocyte subpopulations implicated dendritic cells but not monocytes in the regulation of CpG ODN-induced IFN secretion. Thus, the cellular pattern of CpG ODN-induced responses in cattle shared many similarities with human leukocytes. Collectively, these analyses revealed substantial conservation of TLR9 structure and TLR9 function in blood leukocytes of humans, cattle and other domestic species.

Animals↗
PubMed1999

Effects of histamine H3 receptor agonists and antagonists on cognitive performance and scopolamine-induced amnesia.

In previous research we found that pre-training administration of histamine H3 receptor agonists such as (R)-alpha-methylhistamine and imetit impaired rat performance in object recognition and a passive avoidance response at the same doses at which they inhibited the release of cortical acetylcholine in vivo. Conversely, in the present study we report that the post-training administration of (R)-alpha-methylhistamine and imetit failed to affect rat performance in object recognition and a passive avoidance response, suggesting that H3 receptor influences the acquisition and not the recall processes. We also investigated the effects of two H3 receptor antagonists, thioperamide and clobenpropit, in the same behavioral tasks. Pre-training administration of thioperamide and clobenpropit failed to exhibit any procognitive effects in normal animals but prevented scopolamine-induced amnesia. However, also post-training administration of thioperamide prevented scopolamine-induced amnesia. Hence, the ameliorating effects of scopolamine-induced amnesia by H3 receptor antagonism are not only mediated by relieving the inhibitory action of cortical H3 receptors, but other mechanisms are also involved. Nevertheless, H3 receptor antagonists may have implications for the treatment of degenerative disorders associated with impaired cholinergic function.

Amnesia↗
PubMed1986

Fine-specificity analysis of antibodies directed to the C-terminal peptides of cytochrome c recognized by T-lymphocytes.

Recognition of cytochrome c by T-lymphocytes seems to involve the amino acid residues in the C-terminal region of the molecule. Lys-99 has particularly been identified as one of the critical residues in the recognition process. We have now raised antibodies against the C-terminal region of the cytochrome c molecule to map the residues that may be recognized by B-lymphocytes. These antibodies were generated in high-responder B10.A mice against either the 81-104 CNBr fragment of pigeon cytochrome c or against the synthetic spliced fragment (86-90)-(94-103) of the tobacco hornworm moth cytochrome c. A good antibody response was obtained for both fragments as measured by solid-phase radioimmunoassay. A series of peptides related to these fragments were synthesized for competitive inhibition to assess the antigenic sites on these molecules. In spite of substantial homology between the moth (86-90)-(94-103) and pigeon (81-104) fragments, the antibody populations raised against each fragment differed in their recognition patterns. Residues 99 (Lys), 103 (Ala) and 104 (Lys) were found to be crucial for binding of the anti-pigeon antibody to the pigeon 81-104 fragment. The fine specificity mapping of the antigenic sites on the moth (86-90)-(94-103) fragment indicated that along with some of the residues in the N-terminus (86-90), residue 99 (Lys) was involved in recognition of the moth (86-90)-(94-103) fragment by its antibody. This residue (Lys-99) also acts as a T-cell receptor contact site for both pigeon and moth cytochrome c. We therefore conclude that common patterns of recognition must exist between T and B-cells that recognize the C-terminal region of cytochrome c. Since Lys-99 is also present in mouse cytochrome c, the antigenic site must involve both self and non-self residues.

Amino Acid Sequence↗
PubMed2003

The mechanisms controlling the recognition of tumor- and virus-infected cells by NKp46.

The destruction of viral-infected and tumor cells is mediated in part via the lysis receptor of natural killer (NK) cells, NKp46. The nature, however, of its lysis ligands expressed on target cells is poorly defined. Recently, we have identified a novel functional interaction between the lysis receptors NKp46 and NKp44 and the hemagglutinin of influenza and hemagglutinin-neuroaminidase of Sendai viruses. This recognition depends on the sialylation of NKp46 and NKp44 receptors. In this study, we expand the significance of these observations by demonstrating a conserved pattern of NKp46 and NKp44 recognition by various hemagglutinins derived from different viral strains. We further establish that this recognition is direct and mainly mediated via alpha2,6-linked sialic acid carried by NKp46. In addition, we demonstrate that the ability of NKp46 to recognize target cells is confined to the membrane proximal domain, and largely relies on the highly conserved sugar-carrying residue, Thr 225. This residue plays a critical dual role in NKp46 interactions with both viral hemagglutinins and the unknown tumor ligands via different mechanisms. These results may explain the ability of NK cells to kill such a broad spectrum of viral-infected and tumor cells.

Animals↗
PubMedDate not supplied

Chemometric analysis of ligand receptor complementarity: identifying Complementary Ligands Based on Receptor Information (CoLiBRI).

We have developed a novel structure-based chemoinformatics approach to search for Complimentary Ligands Based on Receptor Information (CoLiBRI). CoLiBRI is based on the representation of both receptor binding sites and their respective ligands in a space of universal chemical descriptors. The binding site atoms involved in the interaction with ligands are identified by the means of a computational geometry technique known as Delaunay tessellation as applied to X-ray characterized ligand-receptor complexes. TAE/RECON multiple chemical descriptors are calculated independently for each ligand as well as for its active site atoms. The representation of both ligands and active sites using chemical descriptors allows the application of well-known chemometric techniques in order to correlate chemical similarities between active sites and their respective ligands. We have established a protocol to map patterns of nearest neighbor active site vectors in a multidimensional TAE/RECON space onto those of their complementary ligands and vice versa. This protocol affords the prediction of a virtual complementary ligand vector in the ligand chemical space from the position of a known active site vector. This prediction is followed by chemical similarity calculations between this virtual ligand vector and those calculated for molecules in a chemical database to identify real compounds most similar to the virtual ligand. Consequently, the knowledge of the receptor active site structure affords straightforward and efficient identification of its complementary ligands in large databases of chemical compounds using rapid chemical similarity searches. Conversely, starting from the ligand chemical structure, one may identify possible complementary receptor cavities as well. We have applied the CoLiBRI approach to a data set of 800 X-ray characterized ligand-receptor complexes in the PDBbind database. Using a k nearest neighbor (kNN) pattern recognition approach and variable selection, we have shown that knowledge of the active site structure affords identification of its complimentary ligand among the top 1% of a large chemical database in over 90% of all test active sites when a binding site of the same protein family was present in the training set. In the case where test receptors are highly dissimilar and not present among the receptor families in the training set, the prediction accuracy is decreased; however, CoLiBRI was still able to quickly eliminate 75% of the chemical database as improbable ligands. CoLiBRI affords rapid prefiltering of a large chemical database to eliminate compounds that have little chance of binding to a receptor active site.

Algorithms↗
PubMed2001

Synaptic pattern formation during cellular recognition.

Cell-cell recognition often requires the formation of a highly organized pattern of receptor proteins (a synapse) in the intercellular junction. Recent experiments [e.g., Monks, C. R. F., Freiberg, B. A., Kupfer, H., Sciaky, N. & Kupfer, A. (1998) Nature (London) 395, 82-86; Grakoui, A., Bromley, S. K., Sumen, C., Davis, M. M., Shaw, A. S., Allen, P. M. & Dustin, M. L. (1999) Science 285, 221-227; and Davis, D. M., Chiu, I., Fassett, M., Cohen, G. B., Mandelboim, O. & Strominger, J. L. (1999) Proc. Natl. Acad. Sci. USA 96, 15062-15067] vividly demonstrate a complex evolution of cell shape and spatial receptor-ligand patterns (several microns in size) in the intercellular junction during immunological synapse formation. The current view is that this dynamic rearrangement of proteins into organized supramolecular activation clusters is driven primarily by active cytoskeletal processes [e.g., Dustin, M. L. & Cooper, J. A. (2000) Nat. Immunol. 1, 23-29; and Wulfing, C. & Davis, M. M. (1998) Science 282, 2266-2269]. Here, aided by a quantitative analysis of the relevant physico-chemical processes, we demonstrate that the essential characteristics of synaptic patterns observed in living cells can result from spontaneous self-assembly processes. Active cellular interventions are superimposed on these self-organizing tendencies and may also serve to regulate the spontaneous processes. We find that the protein binding/dissociation characteristics, protein mobilities, and membrane constraints measured in the cellular environment are delicately balanced such that the length and time scales of spontaneously evolving patterns are in near-quantitative agreement with observations for synapse formation between T cells and supported membranes [Grakoui, A., Bromley, S. K., Sumen, C., Davis, M. M., Shaw, A. S., Allen, P. M. & Dustin, M. L. (1999) Science 285, 221-227]. The model we present provides a common way of analyzing immunological synapse formation in disparate systems (e.g., T cell/antigen-presenting cell junctions with different MHC-peptides, natural killer cells, etc.).

Animals↗
PubMed2005

Automated evaluation of Her-2/neu status in breast tissue from fluorescent in situ hybridization images.

The evaluation of fluorescent in situ hybridization (FISH) images is one of the most widely used methods to determine Her-2/neu status of breast samples, a valuable prognostic indicator. Conventional evaluation is a difficult task since it involves manual counting of dots in multiple images. In this paper, we present a multistage algorithm for the automated classification of FISH images from breast carcinomas. The algorithm focuses not only on the detection of FISH dots per image, but also on combining results from multiple images taken from a slice for overall case classification. The algorithm includes mainly two stages for nuclei and dot detection respectively. The dot segmentation consists of a top-hat filtering stage followed by template matching to separate real signals from noise. Nuclei segmentation includes a nonlinearity correction step, global thresholding to identify candidate regions, and a geometric rule to distinguish between holes within a nucleus and holes between nuclei. Finally, the marked watershed transform is used to segment cell nuclei with markers detected as regional maxima of the distance transform. Combining the two stages allows the measurement of FISH signals ratio per cell nucleus and the collective classification of cases as positive or negative. The system was evaluated with receiver operating characteristic analysis and the results were encouraging for the further development of this method.

Algorithms↗
PubMed2006

MAMPs and MIMPs: proposed classifications for inducers of innate immunity.

Plants encode a sophisticated innate immune system. Resistance against potential pathogens often relies on active responses. Prerequisite to the induction of defences is recognition of the pathogenic threat. Significant advances have been made in our understanding of the non-self molecules that are recognized by plants and the means by which plants perceive them. Established terms describing these recognition events, including microbe-associated molecular pattern (MAMP), MAMP-receptor, effector, and resistance (R) protein, need clarification to represent our current knowledge adequately. In this review we propose criteria to classify inducers of plant defence as either MAMPs or microbe-induced molecular patterns (MIMPs). We refine the definition of MAMP to mean a molecular sequence or structure in ANY pathogen-derived molecule that is perceived via direct interaction with a host defence receptor. MIMPs are modifications of host-derived molecules that are induced by an intrinsic activity of a pathogen-derived effector and are perceived by a host defence receptor. MAMP-receptors have previously been classified separately from R-proteins as a discrete class of surveillance molecules. However, MAMP-receptors and R-proteins cannot be distinguished on the basis of their protein structures or their induced responses. We propose that MAMP-receptors and MIMP-receptors are each a subset of R-proteins. Although our review is based on examples from plant pathogens and plants, the principles discussed might prove applicable to other organisms.

Immunity, Innate↗
PubMed1998

Necessity of acetylcholine for retinal directionally selective responses to drifting gratings in rabbit.

1. A model for retinal directional selectivity postulates that GABAergic inhibition of responses to motions in the null (anti-preferred) direction underlies this selectivity. An alternative model postulates that besides this inhibition, there exists an asymmetric, nicotinic acetylcholine (ACh) input from starburst amacrine cells. It is possible for the latter but not the former model that stimuli could exist such that nicotinic blockade eliminates directional selectivity. Such stimuli would drive the cholinergic but not the GABAergic system well. 2. So far, attempts to eliminate directional selectivity with nicotinic blockade have failed, but they always used isolated, moving bars as the stimulus. We confirmed this failure for On-Off directionally selective (DS) ganglion cells in our preparation of the rabbit's retina. 3. However, while recording from these cells, we discovered that nicotinic blockade eliminated directional selectivity to drifting, low spatial frequency sine- and square-wave gratings. 4. This effect was not just due to the smallness of the responses under nicotinic blockade. NMDA blockade caused even smaller responses, but no loss of directional selectivity. 5. This result is consistent with a two-asymmetric-pathways model of directional selectivity, but inconsistent with an asymmetric-GABA-only model. 6. We conclude that asymmetric nicotinic inputs extend the range of stimuli that can elicit directional selectivity to include moving textures, that is, those with multiple peaks in their spatial luminance profile.

Acetylcholine↗
PubMed2006

Neutrophil influx during non-typhoidal salmonellosis: who is in the driver's seat?

A massive neutrophil influx in the intestine is the histopathological hallmark of Salmonella enterica serovar Typhimurium-induced enterocolitis in humans. Two major hypotheses on the mechanism leading to neutrophil infiltration in the intestinal mucosa have emerged. One hypothesis suggests that S. enterica serovar Typhimurium takes an active role in triggering this host response by injecting proteins, termed effectors, into the host cell cytosol which induce a proinflammatory gene expression profile in the intestinal epithelium. The second hypothesis suggests a more passive role for the pathogen by proposing that bacterial invasion stimulates the innate pathways of inflammation because the pathogen-associated molecular patterns of S. enterica serovar Typhimurium are recognized by pathogen recognition receptors on cells in the lamina propria. A review of the current literature reveals that, while pathogen recognition receptors are clearly involved in eliciting neutrophil influx during S. enterica serovar Typhimurium infection, a direct contribution of effectors in triggering proinflammatory host cell responses cannot currently be ruled out.

Enterocolitis↗
PubMed2000

Neuroscience. Boosting working memory.

Working out which areas of the brain become activated during the formation of working (short-term) memory has been greatly helped by functional magnetic resonance imaging (fMRI). In a Perspective, Robbins et al. discuss new findings (Furey et al.) with fMRI that reveal how working memory is enhanced by the drug physostigmine, which increases cholinergic function in the brain.

Acetylcholine↗
PubMed2005

Memory function in women with premenstrual complaints and the effect of serotonergic stimulation by acute administration of an alpha-lactalbumin protein.

Serotonergic hypofunction may underlie at least part of the symptoms that are experienced by women with premenstrual complaints, including memory deficits. In the current study we investigated changes in memory functions in the premenstrual phase compared to the early postmenstrual phase in 16 women with premenstrual complaints. In addition, the effect of an acute serotonergic stimulation by administration of an alpha-lactalbumin protein on premenstrual memory performance was assessed using a double-blind placebo-controlled crossover design. It was found that both short-term and long-term memory for words (30-word learning task) and abstract figures (abstract visual learning task) were mildly impaired in the premenstrual phase. Administration of alpha-lactalbumin during the premenstrual phase could only partially attenuate the memory performance decrements that are seen in the premenstrual phase. Specifically, alphalactalbumin improved long-term memory for abstract figures, but not for words. There were no effects of menstrual phase or alpha-lactalbumin on planning functions (computerized Tower of London). The data suggest that serotonergic hypofunction may play a role in premenstrual memory decline, but serotonergic mechanisms cannot fully account for observed cognitive changes in the premenstrual phase.

Adolescent↗
PubMed2006

Generation of time delays: simplified models of intracellular signalling in cerebellar Purkinje cells.

In many neuronal systems, information is encoded in temporal spike patterns. The recognition and storage of temporal patterns requires the generation and modulation of time delays between inputs and outputs. In cerebellar Purkinje cells, stimulation of metabotropic glutamate receptors (mGluRs) results in a delayed calcium and voltage response that has been implicated in classical conditioning and temporal pattern recognition. Here, we analyse and simplify a complex model of the intracellular signalling network that has been proposed as a substrate for this delayed response. We systematically simplify the original model, present a minimal model of time delay generation, and show that a delayed response can be produced by the combination of negative feedback and autocatalysis, without any intervening signalling steps that would contribute additive delays. The minimal model is analysed using phase plane methods, and classified as an excitable system. We discuss the implication of excitability for computations performed by intracellular signalling networks in general.

Animals↗
PubMed1999

Properties of extracellular polysaccharides of potato ring rot pathogen and corresponding recognition sites of potato cell walls.

The properties of extracellular polysaccharides of the potato ring rot pathogen Clavibacter michiganensis subsp. sepedonicus (Cms) and the corresponding recognition sites isolated from cell walls of potato suspension cultures have been studied. Extracellular polysaccharides of Cms consist of 4-6 components, which differ greatly in molecular mass (from <1 kD to >700 kD), and are capable of formation of associates stabilized by electrostatic interactions in the presence of calcium. Using affinity column chromatography, sites possessing affinity for the total extracellular polysaccharide complex of Cms were isolated from cell walls of suspension cultures of three potato varieties with different resistance to the pathogen. The content of the receptor sites consisting of glycopeptides and sugars for the variety devoid of resistance was 10 times greater than that for the resistant variety. In the receptor fraction for the latter variety, only sugars were found. The molecular masses of the components of the receptor fraction of cell walls were from 39 to 86 kD. Polypeptides in the recognition sites for the resistant variety escaped detection in electrophoretic patterns. Study of the amino acid composition of the receptor sites of cell walls showed that the sites of the resistant variety contained trace amounts of only seven amino acids. In the sites of the receptive variety 14 amino acids were found, the content of polar amino acids being twice as large as that of nonpolar amino acids. Among polar amino acids, glutamine and glycine prevailed, whereas among nonpolar amino acids valine was dominant. We suggest that one of the reasons of variety-specific resistance of potato to Cms is the absence or a low content of the sites revealing the affinity for bacterial extracellular polysaccharides on the plant cell surface.

Actinomycetales↗