Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Origin Recognition Complex”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 793 records · Page 44Linked to original sources

Molecular basis of human 46X,Y sex reversal revealed from the three-dimensional solution structure of the human SRY-DNA complex.

The solution structure of the specific complex between the high mobility group (HMG) domain of SRY (hSRY-HMG), the protein encoded by the human testis-determining gene, and its DNA target site in the promoter of the müllerian inhibitory substance gene has been determined by multidimensional NMR spectroscopy. hSRY-HMG has a twisted L shape that presents a concave surface (made up of three helices and the N- and C-terminal strands) to the DNA for sequence-specific recognition. Binding of hSRY-HMG to its specific target site occurs exclusively in the minor groove and induces a large conformational change in the DNA. The DNA in the complex has an overall 70 degrees-80 degrees bend and is helically unwound relative to classical A- and B-DNA. The structure of the complex reveals the origin of sequence-specific binding within the HMG-1/HMG-2 family and provides a framework for understanding the effects of point mutations that cause 46X,Y sex reversal at the atomic level.

Anti-Mullerian Hormone↗

Flexibility in T-cell receptor ligand repertoires depends on MHC and T-cell receptor clonotype.

T-cell receptors (TCR) recognize peptides complexed to self-major histocompatibility complex (MHC) molecules. Recognition of peptide/MHC ligands by the TCR is highly peptide specific. However, certain TCRs can also recognize sequence-related and -unrelated ('mimicry') epitopes presented by homologous MHC molecules. Using two human, human leucocyte antigen-DR1 (HLA-DR1)-restricted T-cell clones specific for HA p307-319, we identified several diverse combinations of peptide-MHC complexes that are functionally equivalent in their ability to trigger T-cell stimulation. These findings demonstrate that a single TCR can productively interact with different peptides complexed to self- as well as non-self-MHC molecules. This extended reactivity is human leucocyte antigen (HLA) allele and TCR clonotype dependent, as the peptide repertoire recognized depends on the presenting HLA-DR molecule and varies among different TCRs that both recognize the HA p307-319/DR1 complex. Importantly, certain peptide analogues can completely change the HLA-restriction pattern of the TCR: T-cell recognition of the wild-type peptide that was absent in the context of a non-self HLA-DR molecule, was restored by complementing substitutions in altered peptide ligands, that could not be presented by the original restriction element. This mechanism may play an important role in allorecognition.

Amino Acid Sequence↗

Binding specificity of a monoclonal anti-DNA antibody.

To investigate the interaction of DNA and anti-DNA antibodies in the immune complex disease of systemic lupus erythematosus, the fine specificity of binding of a monoclonal anti-DNA antibody was determined. This antibody, termed Cll, was derived from the fusion of spleen cells from an autoimmune MRL-lpr/lpr mouse with the myeloma cell line M45. In a solid-phase ELISA assay to measure anti-DNA activity, Cll showed preference for single stranded compared to double stranded DNA of animal origin. The Cll antibody also bound some deoxyribohomopolymers as well as ribohomopolymers, but failed to bind synthetic DNA duplexes. Defined size oligonucleotides with a size range of 2-(12-18) failed to inhibit the binding of Cll to single stranded DNA. This pattern of binding is consistent with the recognition of a unique structural determinant that can be represented by a variety of nucleic acids. The absence of antigenic activity among the oligonucleotides suggests that an extended polynucleotide structure is required for antibody binding, possibly because of a bivalent or 'monogamous' mode of interaction. The binding properties of Cll further suggest that its ability to participate in immune complex formation may be limited by the nature of the available DNA antigen.

Aged↗

I-J as an idiotype of the recognition component of antigen-specific suppressor T-cell factor.

The I-J determinant of membrane glycoprotein is known to be expressed exclusively on suppressor T cells (TS), which have a crucial role in the regulation of immune responses. I-J also comprises part of the soluble factor (TSF) with suppressor activity which is secreted from TS. Gene-mapping experiments have indicated that the I-J gene lies between the I-A and I-E subregions of the mouse major histocompatibility complex (MHC) and is defined by the H-2 congeneic pair, that is, B10.A(3R) and B10.A(5R). In fact, antibodies raised in the reciprocal combinations of B10.A(3R) and B10.A(5R) define the I-Jb and I-Jk alleles, and are able to detect the I-J determinants on TS and TSF. Biochemical and functional analyses, using I-J-positive TS clones and hybridomas, have demonstrated that monoclonal anti-I-J antibodies precipitate I-Jk or I-Jb with a relative molecular mass of 25,000-28,000 (25-28K) and that the I-J+ molecule mediates the restriction specificity of TSF in association with an antigen-binding protein (45K). However, molecular genetic studies on the I-J gene reveal no genetic difference between B10.A(3R) and B10.A(5R) and also that there is no room to accommodate a gene encoding I-J in the expected I region. These discrepancies between the molecular genetic and serological/functional data require explanation. Here we demonstrate that TS and TSF expressing I-J of the host type were produced by fully allogeneic bone marrow cells of donor origin in chimaeric mice, when the chimaeras received the host antigen-presenting cells (APC) at the time of immunization. The results show that APC are necessary for the activation and clonal expansion of TS and also support the notion that I-J is an idiotypic determinant of the recognition component of TS and TSF.

Animals↗

Characterization and pattern recognition of oil-sand naphthenic acids using comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry.

Oil-sand naphthenic acids (NAs) are organic wastes produced during the oil-sand digestion and extraction processes and are very difficult to separate and analyze as individual components due to their complex compositions. A comprehensive two-dimensional gas chromatography/time of flight mass spectrometry (GC x GC/TOF-MS) system was applied for the characterization of two commercial mixtures of naphthenic acids (Fluka and Acros) and a naphthenic acid sample extracted from the Syncrude tailings. Contour plots of chromatographic distributions of different Z homologous series of the Fluka, Acros and Syncrude NAs were constructed using fragment ions that were characteristic of the NA's molecular structures. Well-ordered patterns were observed for NAs of Z= 0 and -2 which corresponded to acyclic acids and monocyclic acids, respectively. For NAs of Z= -4, -6, and -8, specific zones were observed which would allow the pattern recognition of these NAs obtained from different origins. As expected, gas chromatographic retention times increase with the number of the carbons and the number of rings in the molecules. Little signal was obtained for NAs with Z numbers of -10, or lower. Deconvoluted mass spectra of various NA isomers were derived from the reconstructed GC x GC chromatogram, permitting detailed structural elucidations for NAs in the future. The current study demonstrated that the combination of GC x GC and the TOF-MS is a powerful to identify origins of the NAs in an effective manner. GC x GC/TOF-MS alone, however, may not be enough to characterize each individual isomer in a complex mixture such as NAs. The use of mass deconvolution software followed by library search have thus become necessary to separate and study the mass spectrum of each individual NA component, allowing a detailed identification of the toxic components within the NAs mixture.

Carboxylic Acids↗

A proposed method for the measurement of anesthetist care variability.

OBJECTIVE: Some critical events in anesthesiology occur as seemingly preventable misadventures, their exact origins indeterminable. Inexperienced anesthetists, anesthesia machine malfunctions, lack of vigilance and human error inevitably initiate some incidents. Anesthesia training improves recognition and decision-making. Avoiding crisis initiation and amelioration of those that do occur is one role of the consultant anesthesiologist. Safe patient care requires medical and procedural knowledge, technical expertise, and control of resources in a complex milieu. Anesthesia simulators are clinical laboratories where anesthetists can sharpen both cognitive and manual skills. Dynamic scenarios allow opportunities for anesthetists to explore and experience crises as they develop and apply their knowledge while attempting to manage these events. Simulator-based scenarios are reproducible and large amounts of useful data can be collected and saved. The authors hypothesize these data can be utilized to compare performance of anesthetists and to measure improvement of individual anesthetists over time. METHODS: We have designed "Stable Anesthesia," a prototypic scenario to test anesthetists' capabilities under the stress of performance guidelines. Three subjects performed anesthesia using the simulator and this protocol. Data from the simulator were archived by the system and analyzed by the authors. RESULTS: A simple mathematical analysis gave good separation of data from three subjects of different training level. CONCLUSIONS: It is suggested that the use of the techniques mentioned here may be of value in the development of a standardized testing protocol for anesthetists.

Anesthesiology↗

Human tyrosyl-tRNA synthetase shares amino acid sequence homology with a putative cytokine.

To test the hypothesis that tRNATyr recognition differs between bacterial and human tyrosyl-tRNA synthetases, we sequenced several clones identified as human tyrosyl-tRNA synthetase cDNAs by the Human Genome Project. We found that human tyrosyl-tRNA synthetase is composed of three domains: 1) an amino-terminal Rossmann fold domain that is responsible for formation of the activated E.Tyr-AMP intermediate and is conserved among bacteria, archeae, and eukaryotes; 2) a tRNA anticodon recognition domain that has not been conserved between bacteria and eukaryotes; and 3) a carboxyl-terminal domain that is unique to the human tyrosyl-tRNA synthetase and whose primary structure is 49% identical to the putative human cytokine endothelial monocyte-activating protein II, 50% identical to the carboxyl-terminal domain of methionyl-tRNA synthetase from Caenorhabditis elegans, and 43% identical to the carboxyl-terminal domain of Arc1p from Saccharomyces cerevisiae. The first two domains of the human tyrosyl-tRNA synthetase are 52, 36, and 16% identical to tyrosyl-tRNA synthetases from S. cerevisiae, Methanococcus jannaschii, and Bacillus stearothermophilus, respectively. Nine of fifteen amino acids known to be involved in the formation of the tyrosyl-adenylate complex in B. stearothermophilus are conserved across all of the organisms, whereas amino acids involved in the recognition of tRNATyr are not conserved. Kinetic analyses of recombinant human and B. stearothermophilus tyrosyl-tRNA synthetases expressed in Escherichia coli indicate that human tyrosyl-tRNA synthetase aminoacylates human but not B. stearothermophilus tRNATyr, and vice versa, supporting the original hypothesis. It is proposed that like endothelial monocyte-activating protein II and the carboxyl-terminal domain of Arc1p, the carboxyl-terminal domain of human tyrosyl-tRNA synthetase evolved from gene duplication of the carboxyl-terminal domain of methionyl-tRNA synthetase and may direct tRNA to the active site of the enzyme.

Amino Acid Sequence↗

Immune complex antigens as a tool in serodiagnosis of kala-azar.

The 63 kDa surface antigen of Leishmania promastigotes is one of the most important virulent factors in establishing the host parasite relationship. This glycoprotein is revealed by surface iodination study as well as by metabolic labeling and immunoblot methods. In search of this specific antigen for serodiagnosis, immune complexes (ICs) were isolated from kala-azar patient sera and analysed by SDS-PAGE and Western immunoblotting. The immunoblot of kala-azar IC with patient sera, anti-promastigote sera and anti gp63 sera detected the major antigen of 55 kDa. This recognition suggests that 55 kDa antigen and gp63 have common antigenic epitope(s). Normal IC did not react with anti gp63 sera indicating absence of this antigen in normal IC. To confirm the parasitic origin of the 55 kDa antigen of kala-azar IC, in vitro IC was formed with parasite antigen and acid dissociated kala-azar IC antibody. This indicated the antigenic similarity of the 55 kDa antigen and gp63 antigen of the parasite. This also suggested that the former antigen may have been processed from gp63. In summary, identification of parasite antigen (55 kDa) in IC of kala-azar patients' sera may be useful in developing a serodiagnostic assay of visceral leishmaniasis. Several other antigens are visualized in kala-azar IC when developed with patient sera. But specificity and efficacy of these antigens have not yet been evaluated in serodiagnosis of the disease.

Animals↗

Liver tissue graft rejection in murine major histocompatibility complex mutants.

Liver tissue grafts between seven H-2 mutants and their parental strains have been studied. Each of these mutants was originally identified by reciprocal mutant--parental strain skin graft rejection. However, liver grafts among mutants and parental standard strains are not uniformly rejected. Liver graft rejection also fails to correlate with mutant--parental stimulation on CML and MLC. In addition, the immune reaction pattern of female mutant animals against grafts of male liver differs from the reaction pattern found in parental standard strains. Several explanations for the differences between immune response to liver and skin grafts are proposed, including different T cell subsets involved in recognition, availability of antigenic sites to immunocompetent cells, and structural differences between mutant and parental H-2 antigens.

Animals↗

Structural basis for molecular recognition in an affibody:affibody complex.

Affibody molecules constitute a class of engineered binding proteins based on the 58-residue three-helix bundle Z domain derived from staphylococcal protein A (SPA). Affibody proteins are selected as binders to target proteins by phage display of combinatorial libraries in which typically 13 side-chains on the surface of helices 1 and 2 in the Z domain have been randomized. The Z(Taq):anti-Z(Taq) affibody-affibody complex, consisting of Z(Taq), originally selected as a binder to Taq DNA polymerase, and anti-Z(Taq), selected as binder to Z(Taq), is formed with a dissociation constant K(d) approximately 100 nM. We have determined high-precision solution structures of free Z(Taq) and anti-Z(Taq), and the Z(Taq):anti-Z(Taq) complex under identical experimental conditions (25 degrees C in 50 mM NaCl with 20 mM potassium phosphate buffer at pH 6.4). The complex is formed with helices 1 and 2 of anti-Z(Taq) in perpendicular contact with helices 1 and 2 of Z(Taq). The interaction surface is large ( approximately 1670 A(2)) and unusually non-polar (70 %) compared to other protein-protein complexes. It involves all varied residues on anti-Z(Taq), most corresponding (Taq DNA polymerase binding) side-chains on Z(Taq), and several additional side-chain and backbone contacts. Other notable features include a substantial rearrangement (induced fit) of aromatic side-chains in Z(Taq) upon binding, a close contact between glycine residues in the two subunits that might involve aliphatic glycine Halpha to backbone carbonyl hydrogen bonds, and four hydrogen bonds made by the two guanidinium N(eta)H(2) groups of an arginine side-chain. Comparisons of the present structure with other data for affibody proteins and the Z domain suggest that intrinsic binding properties of the originating SPA surface might be inherited by the affibody binders. A thermodynamic characterization of Z(Taq) and anti-Z(Taq) is presented in an accompanying paper.

Amino Acid Sequence↗

[Determination of optimal complexity for long ECG sequence].

In this article is reported a study on the optimal complexity of the long electrocardiogram (ECG) signal. At first, the original signal sequence was symbolized, then its complexity was calculated by Lempel-Ziv algorithm, and different factors of the complexity were discussed, and three different kinds of ECG signals, i.e., normalcy, angina and myocardial infarction, were studied. The results indicate that the optimal threshold-value to symbolize the original signal and the optimal signal length are two main factors that affect the complexity value, and the optimal complexity value can effectively distinguish normal ECG and patients' ECG.

Algorithms↗

Molecular dynamics simulations of galectin-1-oligosaccharide complexes reveal the molecular basis for ligand diversity.

Galectin-1 is a member of a protein family historically characterized by its ability to bind carbohydrates containing a terminal galactosyl residue. Galectin-1 is found in a variety of mammalian tissues as a homodimer of 14.5-kDa subunits. A number of developmental and regulatory processes have been attributed to the ability of galectin-1 to bind a variety of oligosaccharides containing the Gal-beta-(1,4)-GlcNAc (LacNAc(II)) sequence. To probe the origin of this permissive binding, solvated molecular dynamics (MD) simulations of several representative galectin-1-ligand complexes have been performed. Simulations of structurally defined complexes have validated the computational approach and expanded upon data obtained from X-ray crystallography and surface plasmon resonance measurements. The MD results indicate that a set of anchoring interactions between the galectin-1 carbohydrate recognition domain (CRD) and the LacNAc core are maintained for a diverse set of ligands and that substituents at the nonreducing terminus of the oligosaccharide extend into the remainder of a characteristic surface groove. The anionic nature of ligands exhibiting relatively high affinities for galectin-1 implicates electrostatic interactions in ligand selectivity, which is confirmed by a generalized Born analysis of the complexes. The results suggest that the search for a single endogenous ligand or function for this lectin may be inappropriate and instead support a more general role for galectin-1, in which the lectin is able to crosslink heterogeneous oligosaccharides displayed on a variety of cell surfaces. Such binding promiscuity provides an explanation for the variety of adhesion phenomena mediated by galectin-1.

Computer Simulation↗

Association between the Rfp-Y haplotype and the incidence of Marek's disease in chickens.

Certain haplotypes at the major histocompatibility (B) complex (Mhc) of the chicken provide an easily demonstrated influence on tumor formation following infections with Marek's disease virus (MDV). Recognition that there is a second histocompatibility complex of genes in the chicken, Rfp-Y, comprised of Mhc class I and class II genes, some of which are at least transcribed, evokes the question of whether this gene complex might also influence the outcome of MDV infections. To test this hypothesis, pedigree-hatched chicks in families from the original Rfp-Y-defining stock in which three Rfp-Y and two B system haplotypes are segregating were challenged with the RB1B strain of MDV. Birds with the Y3/Y3 genotype were found to have 2.3 times the risk of developing a tumor compared with birds with other Rfp-Y genotypes combined (P <0.02). Additionally, birds carrying the BR9/B11 genotype had 2.3 times the risk of tumor formation, relative to birds with the B11/B11 genotype (P <0.02). We found no evidence for an interaction between genotypes within the B and Rfp-Y systems. These data provide evidence that Rfp-Y haplotypes, as well as B haplotypes, can significantly influence the outcome of infection with MDV.

Animals↗

Unique anomalous origin of the left anterior cerebral artery.

We present the case of an anomalous origin of the left anterior cerebral artery (ACA) from the supraclinoid segment of the right internal carotid artery. Because of improved imaging quality, anomalies of the ACA-anterior communicating artery (AComA) complex are increasingly recognized on transaxial images. Although most of these anomalies are incidental findings of little clinical significance, some ACA-AComA complex anomalies are clinically significant. Recognition of these anomalies may be instrumental in developing a differential diagnosis or for improved surgical planning.

Anterior Cerebral Artery↗

The design of molecular hosts, guests, and their complexes.

The origins, definitions, tools, and guiding principles of host-guest chemistry are developed. Perching, nesting, and capsular complexes are exemplified through molecular model and crystal structure comparisons. The degree of preorganization of a host for binding is a central determinant of its binding power. Complementarity of binding site placement in host and guest is a central determinant of structural recognition in complexation. Examples are given of chiral recognition in complexation, of partial transacylase mimics, of caviplexes, and of a synthetic molecular cell.

Acylation↗

Manganese poisoning reduces strychnine-insensitive glycine binding sites in the globus pallidus of the mouse brain.

Manganese (Mn) poisoning is characterized by central nervous system manifestations, including psychiatric disturbances and extrapyramidal disorders. This metal is thought to produce neuronal degeneration due to cytotoxic products originated by oxidative stress and through an indirect excitotoxic process. In previous studies, we have found a reduction in the density of N-methyl-D-aspartate (NMDA) recognition sites in some brain areas of Mn-treated mice. Due to the close relationship between NMDA sites and strychnine-insensitive glycine (Gly) modulatory sites in the NMDA receptor complex, the [3H]-glycine ([3H]-Gly) binding was analyzed by autoradiographic methods in the brain of mice treated with manganese chloride for 8 weeks. Among all analyzed areas, only the globus pallidus showed a significant reduction in [3H]-Gly binding (27-28%). The Gly binding decrease, focalized in the globus pallidus, could reflect a degeneration of structures containing strychnine-insensitive Gly receptors, since this area is the most frequently reported damaged brain region in Mn intoxication. However, it might also be due to a Gly receptor down-regulation to control NMDA complex activation during Mn poisoning.

Animals↗

T cell response to embryonal carcinoma F9 cells: induction and characterization of T cell receptor alpha beta+ double-negative cytotoxic T lymphocytes.

We investigated the mechanism of T cell response to murine embryonal carcinoma F9 cells. Thy-1+, CD4-, CD8- (double-negative) cytotoxic effector cells were induced in spleen cells obtained from immune A.BY mice to F9 cells, and the cytotoxic activity was major histocompatibility complex (MHC)-unrestricted. Furthermore, CD4+ T cells were essential for the induction of double-negative cytotoxic T lymphocytes directed to F9 cells. Most of the double-negative cytotoxic T lymphocyte lines obtained by long-term culture of the effector cells had CD3 molecule and T-cell receptor beta chain on their cell surface, and the CD3 molecule was found to be involved in target cell recognition. The T cell receptor alpha beta+ double-negative cytotoxic T lymphocyte line (2A5) also lysed various tumor cells in a non-MHC-restricted manner, but did not lyse concanavalin A-stimulated blasts of 129 strain, from which F9 cells had originated. These results indicate that T cell receptor alpha beta+ double-negative cytotoxic T lymphocytes induced by F9 cells recognize a common antigen(s) expressed on F9 cells and other tumor cells but not minor histocompatibility antigens.

Animals↗

Protein-specific cytotoxic T lymphocytes. Recognition of transfectants expressing intracellular, membrane-associated or secreted forms of beta-galactosidase.

BALB/c-derived tumor cells were transfected with recombinant Escherichia coli beta-galactosidase (beta-gal) genes which were inserted into IgM heavy chain gene derivatives, leading to expression of the resulting fusion protein in different cellular compartments. A beta-gal-specific, major histocompatibility complex (MHC) class I-restricted CD8+CD4- cytotoxic T lymphocyte (CTL) line of BALB/c origin raised against one transfectant expressing cytoplasmic beta-gal also lysed transfectants expressing beta-gal as membrane-inserted fusion protein, as well as transfectants secreting beta-gal. Our data show that MHC class I-restricted CTL can recognize fragments of nonviral cellular proteins, be they expressed as intracellular, membrane-inserted, or secreted products. The findings confirm and extend a hypothesis on the nature of minor histocompatibility (H) antigens formulated earlier.

Animals↗