Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Signature”

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 469 records · Page 26Linked to original sources
PubMed2003

Systemic and enteric colonization of pigs by a hilA signature-tagged mutant of Salmonella choleraesuis.

Although host adapted to pigs, Salmonella enterica serovar Choleraesuis (S. choleraesuis) can induce a virulent foodborne salmonellosis in humans. To directly investigate virulence factors of S. choleraesuis, we extended the functional genomics approach of signature-tagged mutagenesis to S. choleraesuis and pigs. When a test pool of 45 randomly signature-tagged null mutants was inoculated orally and intraperitoneally in pigs, one of the mutants that failed to colonize by either route was tagged in hilA. In the broad host range serovar S. typhimurium, hilA regulates invasion genes in the first pathogenicity island and is required for enteric but not systemic infections in mice experimentally infected with S. typhimurium. The pool of tagged S. choleraesuis null mutants was a complex mix inoculated in pigs. When pigs were challenged with an equal mixture of the hilA mutant and wild type bacteria, the hilA mutant was at a competitive disadvantaged (attenuated) in pigs inoculated orally but not in intraperitoneally inoculated pigs. Our data support that hilA in S. choleraesuis infections of pigs has a role in enteric but not systemic infections similar to that of S. typhimurium in the murine model of human typhoid fever. The role of hilA may be conserved across Salmonella serovars and host species.

Administration, Oral↗
PubMed1989

Evaluation of post-cardiopulmonary bypass Sonoclot signatures in patients taking nonsteroidal anti-inflammatory drugs.

Patients who take nonsteroidal anti-inflammatory drugs (NSAID) and who experience bleeding after cardiopulmonary bypass (CPB) are treated empirically with platelet transfusions because of the unavailability of rapid and accurate diagnostic clotting function tests. Therefore, a Sonoclot Analyzer (Sienco, Inc, Morrison, CO), which measures the change in the viscoelastic properties of recalcified whole blood, was used to assess platelet function in 51 patients undergoing CPB for cardiac surgery. Seventeen patients (group 1) taking NSAID were compared with 34 patients who were not taking NSAID (group 2). Blood samples were drawn for Sonoclot analysis before and after CPB. Chest tube drainage was measured for 24 hours postoperatively in both groups. Clot retraction, measured by the down slope on the Sonoclot signature, decreased significantly in group-1 patients, although values obtained for both groups were in the normal range. No difference was found between groups when Sonoclot signatures were compared, requirements for replacement of clotting factors or platelets, chest tube blood drainage, and unscheduled return to the operating room for bleeding. It is concluded that patients taking NSAID did not experience increased bleeding after cardiopulmonary bypass and that empiric platelet transfusion seemed unnecessary. In addition, the Sonoclot Analyzer seems to be a useful and sensitive instrument for rapidly assessing platelet function in the operating room.

Aspirin↗
PubMed2003

Automated data interpretation based on the concept of "negative signature mass" for mass-mapping disulfide structures of cystinyl proteins.

An efficient method for data processing and interpretation is needed to support and extend disulfide mass-mapping methodology based on partial reduction and cyanylation-induced cleavage to proteins containing more than four cystines. Here, the concept of "negative signature mass" is introduced as the novel feature of an algorithm designed to identify the disulfide structure of a cystinyl protein given an input of mass spectral data and an amino acid sequence. The "negative signature mass" process is different from the conventional approach in that it does not directly rule-in disulfide linkages, but rather eliminates linkages from a list of all possible theoretical linkages, with the goal of ruling out enough linkages so that only one disulfide structure can be constructed. The operating principles and the effectiveness of the algorithm are described in the context of analyzing ribonuclease A, a 124-residue protein containing eight cysteines in the form of four cystines (disulfides).

Amino Acid Sequence↗
PubMed2001

Sequence analysis of the aminoacylase-1 family. A new proposed signature for metalloexopeptidases.

The amino acid sequence analysis of the human and porcine aminoacylases-1, the carboxypeptidase S precursor from Saccharomyces cerevisiae, the succinyl-diaminopimelate desuccinylase from Escherichia coli, Haemophilus influenzae and Corynebacterium glutamicum, the acetylornithine deacetylase from Escherichia coli and Dictyostelium discoideum and the carboxypeptidase G(2) precursor from Pseudomonas strain, using the Basic Local Alignment Search Tool (BLAST) and the Position-Specific Iterated BLAST (PSI-BLAST), allowed us to suggest that all these enzymes, which share common functional and biochemical features, belong to the same structural family. The three amino acid blocks which were found to be highly conserved, using the CLUSTAL W program, could be assigned to the catalytic active site, based on the general three-dimensional structure of the carboxypeptidase G(2) from the Pseudomonas strain precursor. Six additional proteins with the same signature have been retrieved after performing two successive PSI-BLAST iterations using the sequence of the conserved motif, namely Lactobacillus delbrueckii aminoacyl-histidine dipeptidase, Streptomyces griseus aminopeptidase, Saccharomyces cerevisiae aminopeptidase Y precursor, two Bacillus stearothermophilus N-carbamyl-L-amino acid amidohydrolases and Pseudomonas sp. hydantoin utilization protein C. The three conserved amino acid motifs corresponded to the following blocks: (i) [S, G, A]-H-x-D-x-V; (ii) G-x-x-D; and (iii) x-E-E. This new sequence signature is clearly different from that commonly reported in the literature for proteins belonging to the ArgE/DapE/CPG2/YscS family.

Amidohydrolases↗
PubMed2001

A comparison of the texture of computed tomography and projection radiography images of vertebral trabecular bone using fractal signature and lacunarity.

The structural integrity of trabecular bone is an important factor characterizing the biomechanical strength of the vertebra, and is determined by the connectivity of the bone network and the trabeculation pattern. These can be assessed using texture measures such as the fractal signature and lacunarity from a high resolution projection radiograph. Using central sections of lumbar vertebrae we compared the results obtained from high-resolution transverse projection images with those obtained from spatially registered low-resolution images from a conventional clinical CT scanner to determine whether clinical CT data can provide useful structural information. Provided the power spectra of the CT images are corrected for image system blurring, the resulting fractal signature is similar for both modalities. Although the CT images are blurred relative to the projection images, with a consequent reduction in lacunarity, the estimated trabecular separation obtained from the lacunarity plots is similar for both modalities. This suggests that these texture measures contain essential information on trabecular microarchitecture, which is present even in low resolution CT images. Such quantitative texture measurements from CT or MRI images are potentially useful in monitoring bone strength and predicting future fracture risk.

Biomechanical Phenomena↗
PubMed2005

Using microarray gene signatures to elucidate mechanisms of antibiotic action and resistance.

Microarray analyses reveal global changes in gene expression in response to environmental changes and, thus, are well suited to providing a detailed picture of bacterial responses to antibiotic treatment. These responses are represented by patterns of gene expression, termed expression signatures, which provide insight into the mechanism of action of antibiotics as well as the general physiological responses of bacteria to antibiotic-related stresses. The complexity of such signatures is challenging the notion that antibiotics act on single targets and this is consistent with the concept that there are multiple targets coupled with common stress responses. A more detailed knowledge of how known antibiotics act should reveal new strategies for antimicrobial drug discovery.

Anti-Bacterial Agents↗
PubMed1998

Global dinucleotide signatures and analysis of genomic heterogeneity.

Early biochemical experiments measuring nearest neighbor frequencies established that the set of dinucleotide relative abundance values (dinucleotide biases) is a remarkably stable property of the DNA of an organism. Analyses of currently available genomic sequence data have extended these earlier results, showing that the dinucleotide biases evaluated for successive 50 kb segments of a genome are significantly more similar to each other than to those of sequences from more distant organisms. From this perspective, the set of dinucleotide biases constitutes a 'genomic signature' that can discriminate sequences from different organisms. The dinucleotide biases appear to reflect species-specific properties of DNA stacking energies, modification, replication, and repair mechanisms. The genomic signature is useful for detecting pathogenicity islands in bacterial genomes.

Bacteria↗
PubMed2003

The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma.

We used gene expression profiling to establish a molecular diagnosis of mantle cell lymphoma (MCL), to elucidate its pathogenesis, and to predict the length of survival of these patients. An MCL gene expression signature defined a large subset of MCLs that expressed cyclin D1 and a novel subset that lacked cyclin D1 expression. A precise measurement of tumor cell proliferation, provided by the expression of proliferation signature genes, identified patient subsets that differed by more than 5 years in median survival. Differences in cyclin D1 mRNA abundance synergized with INK4a/ARF locus deletions to dictate tumor proliferation rate and survival. We propose a quantitative model of the aberrant cell cycle regulation in MCL that provides a rationale for the design of cell cycle inhibitor therapy in this malignancy.

ADP-Ribosylation Factors↗
PubMed2002

Residue-specific mass signatures for the efficient detection of protein modifications by mass spectrometry.

Currently available mass spectrometric (MS) techniques lack specificity in identifying protein modifications because molecular mass is the only parameter used to characterize these changes. Consequently, the suspected modified peptides are subjected to tandem MS/MS sequencing that may demand more time and sample. We report the use of stable isotope-enriched amino acids as residue-specific "mass signatures" for the rapid and sensitive detection of protein modifications directly from the peptide mass map (PMM) without enrichment of the modified peptides. These mass signatures are easily recognized through their characteristic spectral patterns and provide fingerprints for peptides containing the same content of specific amino acid residue(s) in a PMM. Without the need for tandem MS/MS sequencing, a peptide and its modified form(s) can readily be identified through their identical fingerprints, regardless of the nature of modifications. In this report, we demonstrate this strategy for the detection of methionine oxidation and protein phosphorylation. More interestingly, the phosphorylation of a histone protein, H2A.X, obtained from human skin fibroblast cells, was effectively identified in response to low-dose radiation. In general, this strategy of residue-specific mass tagging should be applicable to other posttranslational modifications.

Fibroblasts↗
PubMed2004

Stable-isotope trapping and high-throughput screenings of reactive metabolites using the isotope MS signature.

A highly efficient method has been developed to detect and identify reactive metabolites, using stable-isotope trapping combined with ESI-MS/MS neutral loss scanning. A mixture of glutathione (GSH, gamma-glutamylcysteinylglycine) and the stable-isotope labeled compound (GSX, gamma-glutamylcysteinylglycine-(13)C(2)-(15)N) was used at an equal molar ratio to trap reactive metabolites generated in microsomal incubations. Samples resulting from incubations were cleaned and concentrated by SPE, followed by LC-MS/MS analyses using constant neutral loss scanning for 129 Da (the gamma-glutamyl moiety) to detect formed GSH conjugates. Unambiguous identification of glutathione adducts was greatly facilitated by the presence of a unique MS signature of a prominent isotopic doublet that differs in mass by 3 Da. Further structural characterization of conjugates was achieved with high confidence by subsequently acquiring MS/MS spectra that were featured by neutral losses of 75 and 129 Da for GSH adducts and 78 and 129 Da for isotopic GSX adducts. The reliability of this method was vigorously validated using a number of compounds known to form reactive metabolites. Superior sensitivity was demonstrated by the capability of the current approach to identify reactive metabolites at low abundance. Because of the unique isotopic MS signature, ultrafast analyses of reactive metabolites were accomplished by direct injection of cleaned samples into mass spectrometers for neutral loss scanning. More importantly, this study has demonstrated the feasibility of the current method for completely automated detection of reactive metabolites via computer-assisted pattern recognition.

Carbon Isotopes↗
PubMed2001

Tyrosine Raman signatures of the filamentous virus Ff are diagnostic of non-hydrogen-bonded phenoxyls: demonstration by Raman and infrared spectroscopy of p-cresol vapor.

p-Cresol is a simple molecular model for the para phenolic side chain of tyrosine. Previously, Siamwiza and co-workers [(1975) Biochemistry 14, 4870-4876] investigated p-cresol solutions to identify Raman spectroscopic signatures for different hydrogen-bonding states of the tyrosine phenoxyl group in proteins. They found that the phenolic moiety exhibits an intense Raman doublet in the spectral interval 820-860 cm(-1) and that the doublet intensity ratio (I2/I1, where I2 and I1 are Raman peak intensities of the higher- and lower-wavenumber members of the doublet) is diagnostic of specific donor and acceptor roles of the phenoxyl OH group. The range of the doublet intensity ratio in proteins (0.30 < I2/I1 < 2.5) was shown to be governed by Fermi coupling between the phenolic ring-stretching fundamental nu1 and the first overtone of the phenolic ring-deformation mode nu(16a), such that when the tyrosine phenoxyl proton is a strong hydrogen-bond donor, I2/I1 = 0.30, and when the tyrosine phenoxyl oxygen is a strong hydrogen-bond acceptor, I2/I1 = 2.5. Here, we interpret the Raman and infrared spectra of p-cresol vapor and extend the previous correlation to the non-hydrogen-bonded state of the tyrosine phenoxyl group. In the absence of hydrogen bonding, the Raman intensity of the higher-wavenumber component of the canonical Fermi doublet is greatly enhanced such that I2/I1 = 6.7. Thus, for the non-hydrogen-bonded phenoxyl, the lower-wavenumber member of the Fermi doublet loses most of its Raman intensity. This finding provides a basis for understanding the anomalous Raman singlet signature (approximately 854 cm(-1)) observed for tyrosine in coat protein subunits of filamentous viruses Ff and Pf1 [Overman, S. A., et al. (1994) Biochemistry 33, 1037-1042; Wen, Z. Q., et al. (1999) Biochemistry 38, 3148-3156]. The implications of the present results for Raman analysis of tyrosine hydrogen-bonding states in other proteins are considered.

Capsid↗
PubMed2001

Mutation in the beta-tubulin signature motif suppresses microtubule GTPase activity and dynamics, and slows mitosis.

We introduced a threonine-to-glycine point mutation at position 143 in the "tubulin signature motif" 140Gly-Gly-Gly-Thr-Gly-Ser-Gly146 of Saccharomyces cerevisiae beta-tubulin. In an electron diffraction model of the tubulin dimer, this sequence comes close to the phosphates of a guanine nucleotide bound in the beta-tubulin exchangeable E site. Both the GTP-binding affinity and the microtubule (MT)-dependent GTPase activity of tubulin isolated from haploid tub2-T143G mutant cells were reduced by at least 15-fold, compared to tubulin isolated from control wild-type cells. The growing and shortening dynamics of MTs assembled from alphabeta:Thr143Gly-mutated dimers were also strongly suppressed, compared to control MTs. The in vitro properties of the mutated MTs (slower growing and more stable) are consistent with the effects of the tub2-T143G mutation in haploid cells. The average length of MT spindles in large-budded mutant cells was only 3.7 +/- 0.2 microm, approximately half of the size of MT arrays in large-budded wild-type cells (average length = 7.1 +/- 0.4 microm), suggesting that there is a delay in mitosis in the mutant cells. There was also a higher proportion of large-budded cells with unsegregated nuclei in mutant cultures (30% versus 12% for wild-type cells), again suggesting such a delay. The results show that beta:Thr143 of the tubulin signature motif plays an important role in GTP binding and hydrolysis by the beta-tubulin E site and support the idea that tubulins belong to a family of proteins within the GTPase superfamily that are structurally distinct from the classic GTPases, such as EF-Tu and p21(ras). The data also suggest that MT dynamics are critical for MT function in yeast cells and that spindle MT assembly and disassembly could be coordinated with other cell-cycle events by regulating beta-tubulin GTPase activity.

Amino Acid Motifs↗
PubMed2004

Mandelamide hydrolase from Pseudomonas putida: characterization of a new member of the amidase signature family.

A recently discovered enzyme in the mandelate pathway of Pseudomonas putida, mandelamide hydrolase (MAH), catalyzes the hydrolysis of mandelamide to mandelic acid and ammonia. Sequence analysis suggests that MAH is a member of the amidase signature family, which is widespread in nature and contains a novel Ser-cis-Ser-Lys catalytic triad. Here we report the expression in Escherichia coli, purification, and characterization of both wild-type and His(6)-tagged MAH. The recombinant enzyme was stable, exhibited a pH optimum of 7.8, and was able to hydrolyze both enantiomers of mandelamide with little enantiospecificity. The His-tagged variant showed no significant change in kinetic constants. Phenylacetamide was found to be the best substrate, with changes in chain length or replacement of the phenyl group producing greatly decreased values of k(cat)/K(m). As with another member of this family, fatty acid amide hydrolase, MAH has the uncommon ability to hydrolyze esters and amides at similar rates. MAH is even more unusual in that it will only hydrolyze esters and amides with little steric bulk. Ethyl and larger esters and N-ethyl and larger amides are not substrates, suggesting that the MAH active site is very sterically hindered. Mutation of each residue in the putative catalytic triad to alanine resulted in total loss of activity for S204A and K100A, while S180A exhibited a 1500-fold decrease in k(cat) and significant increases in K(m) values. Overall, the MAH data are similar to those of fatty acid amide hydrolase and support the suggestion that there are two distinct subgroups within the amidase signature family.

Amidohydrolases↗
PubMed1997

Determination of tumor necrosis factor binding protein disulfide structure: deviation of the fourth domain structure from the TNFR/NGFR family cysteine-rich region signature.

Tumor necrosis factor binding protein is a soluble molecule derived from the extracellular domain of the 55 kDa human tumor necrosis factor receptor, which can block the biological function of tumor necrosis factor by binding to the growth factor. This cysteine-rich molecule is subdivided into four domains, each containing six conserved cysteines that form three intrachain disulfide linkages known as the tumor necrosis factor receptor/nerve growth factor receptor family cysteine-rich region signature structure. In an effort to elucidate the molecular integrity of the molecule, we performed detailed analysis and searched for strategies to elucidate the complete disulfide structure of the E. coli-derived tumor necrosis factor binding protein and to determine the disulfide arrangement in the fourth domain of Chinese hamster ovary cell-derived molecule. The methods employed included various proteolytic digestions, peptide mapping, partial reduction, and assignment of disulfides by N-terminal sequencing and matrix-assisted laser desorption ionization mass spectrometry with post-source decay. The first three domains of the molecule were confirmed to have disulfide structures identical to the cysteine-rich region signature structure found in the above-mentioned receptor superfamily. The fourth domain has a different structure from the first three domains where the last four cysteines form two disulfide bonds in opposite positions.

Amino Acid Sequence↗
PubMedDate not supplied

Lesion spectra: radiation signatures and biological gateways.

We describe an integrative approach to the modeling of biophysical radiation effects. The model takes aim at practical applications of the knowledge provided by molecular studies of radiation-matter interactions in DNA. The central proposition is the idea that the distribution of molecular lesions (i.e., a molecular lesion spectrum, MLS) generated in DNA by exposure to a particular radiation is a characteristic of that causal radiation (i.e., is a radiation signature, RS). We have found that adaptive neural networks (ANN's) provide an efficient way to validate that proposition and that ANN's are also likely to be invaluable in any attempt to correlate cancers with radiation types (i.e., with RS's), to use RS's for evaluating individual carcinogenic susceptibilities, and to develop a low-dose personalized monitoring capability. Although efforts to identify products of radiation that are specific to radiation type and to link those with biological responses are almost a century old, the RS concept has provided the first quantitative confirmation of such causal relations. That is, RS's and radiation markers have been identified for various types of radiation, electromagnetic (EM) and particulate, and these signatures and markers may constitute a new way for fast radiation exposure estimates, risk assessment, and cumulative low-dose evaluation. In this work, while we will present a short review of the concepts and methods related to both RS's and markers, almost the entire effort will relate to the modeling and interpretation of RS's using ANN processing.

Biomarkers↗
PubMed2002

Transformation processes, pathways, and possible sources of distinctive polychlorinated dibenzo-p-dioxin signatures in sink environments.

In recent years, studies on environmental samples with unusual dibenzo-p-dioxin (PCDD) congener profiles were reported from a range of countries. These profiles, characterized by a dominance of octachlorinated dibenzodioxin (OCDD) and relatively low in dibenzofuran (PCDF) concentrations, could not be attributed to known sources or formation processes. In the present study, the processes that result in these unusual profiles were assessed using the concentrations and isomer signatures of PCDDs from dated estuarine sediment cores in Queensland, Australia. Increases in relative concentrations of lower chlorinated PCDDs and a relative decrease of OCDD were correlated with time of sediment deposition. Preferred lateral, anaerobic dechlorination of OCDD represents a likely pathway for these changes. In Queensland sediments, these transformations result in a distinct dominance of isomers fully chlorinated in the 1,4,6,9-positions (1,4-patterns), and similar 1,4-patterns were observed in sediments from elsewhere. Consequently, these environmental samples may not reflect the signatures of the original source, and a reevaluation of source inputs was undertaken. Natural formation of PCDDs, which has previously been suggested, is discussed; however, based on the present results and literature comparisons, we propose an alternative scenario. This scenario hypothesizes that an anthropogenic PCDD precursor input (e.g. pentachlorophenol) results in the contamination. These results and hypothesis imply further investigations are warranted into possible anthropogenic sources in areas where natural PCDD formation has been suggested.

Benzofurans↗
PubMed2006

Absolute transcript expression signatures of Cyp and Gst genes in Mus spretus to detect environmental contamination.

We evaluated whether quantitation of mRNA molecules of key genes is a reliable biomonitoring end-point. We examined the Mus spretus expression levels of 19 transcripts encoding different cytochrome-P450s and glutathione transferases. Mice dwelling at the Doñana Biological Reserve were compared to those from an industrial settlement (PS). Metal biomonitoring indicated that PS animals sustained a heavier pollutant burden than those from the reference site. Transcript quantitations showed the following: (i) gender-related differences in the expression of most Cyp and Gst genes; (ii) one PS female displaying much smaller/larger transcript amounts than the remaining females; (iii) the concomitant up-regulation of Cyp1a2, Cyp2a5, Cyp2e1, Cyp4a10, Gsta1, Gsta2, Gstm1, and Gstm2 mRNAs in liver of PS males; and (iv) outstanding qualitative and quantitative differences between the hepatic expression signature of PS males and that promoted by paraquat. We conclude that (i) absolute amounts of transcripts encoding biotransformation enzymes are more potent biomarkers in males than in females, and in liver than in kidney; (ii) individual quantitations prevent biased interpretations by specimens with abnormal expression levels; and (iii)transcript expression signature of PS males is consistent with exposure to a complex profile of organic pollutants, other than oxidative stressors.

Animals↗
PubMed2006

Different spectral signatures of octapeptide 3(10)- and alpha-helices revealed by two-dimensional infrared spectroscopy.

Femtosecond two-dimensional infrared (2D IR) spectroscopy is applied to the amide I modes of the terminally protected homo-octapeptide Z-[L-(alphaMe)Val](8)-OtBu in CDCl(3), 2,2,2-trifluoroethanol (TFE), and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) solutions to acquire 2D spectral signatures that distinguish between 3(10)- and alpha-helix structures. Suppression of diagonal peaks by controlling polarizations of IR pulses clearly reveals cross-peak patterns that are crucial for structural determination. A doublet feature is observed when the peptide ester forms a 3(10)-helix in CDCl(3) and TFE and when it is at the initial stage of 3(10)- to alpha-helix transition in HFIP. In contrast, the 2D IR spectrum shows a multiple peak pattern after the peptide ester has acidolyzed and become an alpha-helix in HFIP. Electronic circular dichroism spectra accompanying the acidolysis-driven conformational change are also reported. This is the first report on the experimental 2D IR signature of a 3(10)-helical peptide. These results, using a model octapeptide, demonstrate the powerful capability of 2D IR spectroscopy to discriminate between different helical structures.

Circular Dichroism↗