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Genetic signatures of coancestry within surnames.

Surnames are cultural markers of shared ancestry within human populations. The Y chromosome, like many surnames, is paternally inherited, so men sharing surnames might be expected to share similar Y chromosomes as a signature of coancestry. Such a relationship could be used to connect branches of family trees, to validate population genetic studies based on isonymy, and to predict surname from crime-scene samples in forensics. However, the link may be weak or absent due to multiple independent founders for many names, adoptions, name changes and nonpaternities, and mutation of Y haplotypes. Here, rather than focusing on a single name, we take a general approach by seeking evidence for a link in a sample of 150 randomly ascertained pairs of males who each share a British surname. We show that sharing a surname significantly elevates the probability of sharing a Y-chromosomal haplotype and that this probability increases as surname frequency decreases. Within our sample, we estimate that up to 24% of pairs share recent ancestry and that a large surname-based forensic database might contribute to the intelligence-led investigation of up to approximately 70 rapes and murders per year in the UK. This approach would be applicable to any society that uses patrilineal surnames of reasonable time-depth.

Chromosomes, Human, Y↗

A unique error signature for human DNA polymerase nu.

Human DNA polymerase nu (pol nu) is one of three A family polymerases conserved in vertebrates. Although its biological functions are unknown, pol nu has been implicated in DNA repair and in translesion DNA synthesis (TLS). Pol nu lacks intrinsic exonucleolytic proofreading activity and discriminates poorly against misinsertion of dNTP opposite template thymine or guanine, implying that it should copy DNA with low base substitution fidelity. To test this prediction and to comprehensively examine pol nu DNA synthesis fidelity as a clue to its function, here we describe human pol nu error rates for all 12 single base-base mismatches and for insertion and deletion errors during synthesis to copy the lacZ alpha-complementation sequence in M13mp2 DNA. Pol nu copies this DNA with average single-base insertion and deletion error rates of 7 x 10(-5) and 17 x 10(-5), respectively. This accuracy is comparable to that of replicative polymerases in the B family, lower than that of its A family homolog, human pol gamma, and much higher than that of Y family TLS polymerases. In contrast, the average single-base substitution error rate of human pol nu is 3.5 x 10(-3), which is inaccurate compared to the replicative polymerases and comparable to Y family polymerases. Interestingly, the vast majority of errors made by pol nu reflect stable misincorporation of dTMP opposite template G, at average rates that are much higher than for homologous A family members. This pol nu error is especially prevalent in sequence contexts wherein the template G is preceded by a C-G or G-C base pair, where error rates can exceed 10%. Amino acid sequence alignments based on the structures of more accurate A family polymerases suggest substantial differences in the O-helix of pol nu that could contribute to this unique error signature.

Amino Acid Sequence↗

Occurrence of organochlorine pesticides (OCPs) and their enantiomeric signatures, and concentrations of polybrominated diphenyl ethers (PBDEs) in the Adélie penguin food web, Antarctica.

Concentrations and enantiomeric signatures of organochlorine pesticides were determined in Antarctic krill, emerald rockcod and Adélie penguin from the Ross Sea, Antarctica. HCB and DDTs were prevalent contaminants in penguin eggs. The highest concentrations of SigmaHCHs (1.35 +/- 0.72 ng/g) were found in the rockcod muscle, where gamma-HCH (1.23 +/- 0.67 ng/g) was the principal isomer. The ratio gamma-HCH/alpha-HCH was evaluated. Enantioselective gas chromatography was used for the evaluation of enantiomeric fractions (EFs) for alpha-HCH and oxychlordane. An increase of 14% in the (+)alpha-HCH enantiomer was found from krill through penguin, suggesting the enantioselective biotransformation increased proportionately with trophic level. Polybrominated diphenyl ethers (PBDEs) were measured and their concentrations were 5.6 +/- 1.12, 5.81 +/- 2.32, 4.57 +/- 0.17 and 3.06 +/- 3.27 ng/g lipids in krill, rockcod muscle, rockcod homogenate and penguin eggs, respectively. The detection of BDE28, BDE47, BDE99 and BDE100 in Antarctic organisms confirmed their global transport and distribution; the detection of lower brominated congeners suggested a potential long-range transport.

Animals↗

Identification of caveolae and their signature proteins caveolin 1 and 2 in the lens.

This study shows that caveolae are present in lens epithelia of rabbit and guinea pig under normal conditions. Caveolae are unique lipid membrane microdomains observed in many cell types. They are believed to play crucial roles in a variety of basic physiological functions including signal transduction, lipid and transcellular transport. Using TEM, immunocytochemistry and immunoblotting we show for the first time the existence of caveolae and the co-localization of their signature marker integral proteins, caveolin-1 and caveolin-2, in the intact lens of rabbit and guinea pig. Thin-section TEM shows that among several species studied, lens epithelia of rabbit and guinea pig exhibited a large number of caveolae. The caveolae were pear shaped, approximately 70 nm in diameter, and were found frequently along the lateral membranes of epithelial cells in the intact lens. In the intact cortical fibers, only a small number of caveolae was seen in the superficial cells. In cultured lens epithelial cells, however, caveolae were observed along all membrane surfaces, but were more abundant at the apical membrane of the cells. Immunofluorescence and immunoblot analyses confirmed the presence of caveolin-1 and caveolin-2 in the lens epithelium. In addition, caveolin-1 and caveolin-2 co-exist in the lens epithelium of both rabbit and guinea pig. HRP tracer study demonstrated that caveolae could carry out endocytosis, suggesting their involvement in molecular transport. Cultured rabbit lens epithelial cells (line N/N1003A) were used to examine the response of caveolae to methyl-beta-cyclodextrin (MBCD), a specific cholesterol-depleting drug. The lens epithelial cells were incubated in freshly prepared MEM medium plus 8% rabbit serum containing 10mm MBCD for 0 (control), 15, 30 or 60 min. Controls for MBCD treatment were cultured in MEM plus 8% rabbit serum. MBCD treatment for 30 min revealed that depletion of cholesterol abolished the majority of caveolae in cultured lens epithelial cells. This result strongly suggests that caveolae are cholesterol-rich lipid rafts that are likely to play important roles in the lens.

Animals↗

Eukaryotic signature proteins of Prosthecobacter dejongeii and Gemmata sp. Wa-1 as revealed by in silico analysis.

The genomes of representatives of three bacterial phyla have been compared with the list of 347 eukaryotic signature proteins (ESPs) derived by Hartman and Fedorov [Proc. Natl. Acad. Sci. USA 99 (2002) 1420]. The species included Prosthecobacter dejongeii of the Verrucomicrobia phylum, Gemmata sp. Wa-1 of the Planctomycetes phylum and Caulobacter crescentus of the Proteobacteria. The protist Trypanosoma brucei was used as a eukaryotic control. P. dejongeii had unique ERGO blast matches to alpha-, beta-, and gamma-tubulin, to Set2, a transcriptional factor associated with eukaryotic DNA, and to LAMMER protein kinase for a total of 10 high-scoring ESP matches altogether. Gemmata sp. Wa-1 shared four of its 17 high-scoring ESP matches with P. dejongeii, and that information coupled with other genomic data provides strong support that these two phyla are related to one another. If the ESP list is an accurate listing of unique eukaryotic proteins, then the low number of high-scoring matches between the proteins of these two bacteria with the list raises doubts about these phyla being direct ancestors of the Eucarya. However, this does not rule out the possibility that ancestral members of either the Verrucomicrobia or Planctomycetes may have played an important role in the evolution of a proto-eukaryotic organism.

Animals↗

Cloning, sequence analysis and expression of the gene encoding a novel wide-spectrum amidase belonging to the amidase signature superfamily from Achromobacter xylosoxidans.

Amidases are very important enzymes for industrial biocatalysis. We scored a novel amidase by screening the Achromobacter xylosoxidans gene library with cephalosporin analogous amides. The gene coding for the enzyme, designated ana, was cloned, sequenced and overexpressed in Escherichia coli. Sequence analysis of ana showed it to be an amidase signature family member. Interestingly, we noted that almost all Ana homologous amidases are from human pathogens responsible for chronic lung infections. Knowing the genetic context of Ana and its homologous amidases, we suggest that they could be a part of transposon structure. Ana can efficiently hydrolyze a series of cephalosporin analogous amides, including amides with an aninine, p-nitro-aninine, and beta-naphthylamine moiety, while cephalosporin could not serve as its substrate.

Achromobacter denitrificans↗

Lessons from signature-tagged mutagenesis on the infectious mechanisms of pathogenic bacteria.

Studies on the genetic basis of bacterial pathogenicity have been undertaken for almost 30 years, but the development of new genetic tools in the past 10 years has considerably increased the number of identified virulence factors. Signature-tagged mutagenesis (STM) is one of the most powerful general genetic approaches, initially developed by David Holden and colleagues in 1995, which has now led to the identification of hundreds of new genes requested for virulence in a broad range of bacterial pathogens. We have chosen to present in this review, the most recent and/or most significant contributions to the understanding of the molecular mechanisms of bacterial pathogenicity among over 40 STM screens published to date. We will first briefly review the principle of the method and its major technical limitations. Then, selected studies will be discussed where genes implicated in various aspects of the infectious process have been identified (including tropism for specific host and/or particular tissues, interactions with host cells, mechanisms of survival and persistence within the host, and the crossing of the blood brain barrier). The examples chosen will cover intracellular as well as extracellular Gram-negative and Gram-positive pathogens.

Bacteria↗

Bayesian analysis of fingerprint, face and signature evidences with automatic biometric systems.

The Bayesian approach provides a unified and logical framework for the analysis of evidence and to provide results in the form of likelihood ratios (LR) from the forensic laboratory to court. In this contribution we want to clarify how the biometric scientist or laboratory can adapt their conventional biometric systems or technologies to work according to this Bayesian approach. Forensic systems providing their results in the form of LR will be assessed through Tippett plots, which give a clear representation of the LR-based performance both for targets (the suspect is the author/source of the test pattern) and non-targets. However, the computation procedures of the LR values, especially with biometric evidences, are still an open issue. Reliable estimation techniques showing good generalization properties for the estimation of the between- and within-source variabilities of the test pattern are required, as variance restriction techniques in the within-source density estimation to stand for the variability of the source with the course of time. Fingerprint, face and on-line signature recognition systems will be adapted to work according to this Bayesian approach showing both the likelihood ratios range in each application and the adequacy of these biometric techniques to the daily forensic work.

Bayes Theorem↗

Unique signatures of highly constrained genes across publicly available genomic databases.

PURPOSE: Publicly available genomic databases are critical in understanding human genetic variation. They also provide unique insights into patterns of genetic constraints and their relationship with human disease. METHODS: We utilized one of the largest publicly available databases, Genome Aggregate Database, to determine genes that are highly constrained for only loss-of-function, only missense, and both loss-of-function/missense variants. We identified their unique signatures and explored their causal relationship with human diseases. Those genes were also evaluated for chromosomal location, tissue-level expression, Gene Ontology analysis, and gene family categorization using multiple publicly available databases. RESULTS: We identified unique patterns of inheritance, protein size, and enrichment in distinct molecular pathways for those constrained genes associated with human disease. In addition, we identified genes that are currently not known to cause human disease, which may be excellent gene discovery candidates. CONCLUSION: We elucidate biological pathways of highly constrained genes that expand our understanding of critical cellular proteins. The findings can also advance research in rare diseases.

Humans↗

Transcript signatures of lymphocytic bronchitis in lung allograft biopsy specimens.

BACKGROUND: Rejection and obliterative bronchiolitis are barriers to sustained graft function in recipients of transplanted lungs. Early detection is hindered by inadequate tests and an incomplete understanding of the molecular events preceding or accompanying graft deterioration. METHODS: Hypothesizing that genes involved in immune responses and tissue remodeling produce biomarkers of rejection, we measured the expression of 192 selected genes in 72 sets of biopsy specimens from human lung allografts. Gene transcripts were quantified using a 2-step, multiplex, real-time polymerase chain reaction approach in endobronchial and transbronchial biopsy specimens from transplant recipients without acute infections undergoing routine surveillance bronchoscopy. RESULTS: Comparisons of histopathology in parallel biopsy specimens identified 6 genes correlating with rejection as manifested by lymphocytic bronchitis, a suspected harbinger of obliterative bronchiolitis. For example, beta2-defensin and collagenase transcripts in inflamed bronchi increased 37-fold and 163-fold, respectively. By contrast, these transcripts did not correlate with acute rejection in transbronchial specimens. Further, no correspondence was noted between histopathologic bronchitis and parenchymal rejection when endobronchial and transbronchial samples were obtained from the same patient. CONCLUSIONS: Our highly sensitive method permits quantitation of many gene transcripts simultaneously in small, bronchoscopically acquired biopsy specimens of allografts. Transcript signatures obtained by this approach suggest that airway and alveolar responses to rejection differ and that endobronchial biopsy specimens assess lymphocytic bronchitis and chronic rejection but are not proxies for transbronchial biopsy specimens. Further, they reveal changes in airway expression of the specific genes involved in host defense and remodeling and suggest that the measurement of transcripts correlating with lymphocytic bronchitis may be diagnostic adjuncts to histopathology.

Adult↗

Analysis of the lineage relationship between mast cells and basophils using the c-kit D816V mutation as a biologic signature.

BACKGROUND: Mast cells and basophils share similar morphologic and functional properties; however, it is not known whether they are derived from a bilineage (basophil/mast cell)-restricted progenitor. OBJECTIVE: To assess whether basophils and mast cells are derived from common committed progenitors using the c-kit D816V mutation as a biologic signature. METHODS: The D816V c-kit mutation found in mast cells of patients with systemic mastocytosis is used as a trackable genetic marker to assess the lineage relationship between mast cells and basophils. Blood and bone marrow aspirates were collected from 33 consecutive patients with mastocytosis with different disease severity. Peripheral blood basophils, monocytes and neutrophils were sorted by immunomagnetic beads. Presence of the D816V c-kit mutation was analyzed by restriction fragment length polymorphism in the genomic DNA and mRNA from sorted cells in all patients and in the genomic DNA of individual basophils of 1 patient. RESULTS: The c-kit D816V mutation was detectable in basophils of 5 patients (15%). All 5 patients had the c-kit mutation also detectable in monocytes and thus had multilineage involvement. Single cell analysis of the genomic DNA in 1 patient showed a similar degree of clonal expansion in basophils, monocytes, and neutrophils. Mutated c-kit was expressed at the mRNA level in all 5 patients. There was no difference in surface Kit expression levels in basophils. CONCLUSION: Basophils carrying the D816V c-kit mutation in mastocytosis were detected only in the context of a multilineage involvement. These results argue against the presence of a bilineage-restricted committed progenitor for mast cells and basophils.

Basophils↗

Isotopic signature of atmospheric xenon released from light water reactors.

A global monitoring system for atmospheric xenon radioactivity is being established as part of the International Monitoring System to verify compliance with the Comprehensive Nuclear-Test-Ban Treaty (CTBT). The isotopic activity ratios of (135)Xe, (133m)Xe, (133)Xe and (131m)Xe are of interest for distinguishing nuclear explosion sources from civilian releases. Simulations of light water reactor (LWR) fuel burn-up through three operational reactor power cycles are conducted to explore the possible xenon isotopic signature of nuclear reactor releases under different operational conditions. It is studied how ratio changes are related to various parameters including the neutron flux, uranium enrichment and fuel burn-up. Further, the impact of diffusion and mixing on the isotopic activity ratio variability are explored. The simulations are validated with reported reactor emissions. In addition, activity ratios are calculated for xenon isotopes released from nuclear explosions and these are compared to the reactor ratios in order to determine whether the discrimination of explosion releases from reactor effluents is possible based on isotopic activity ratios.

Air Pollutants, Radioactive↗

Predicting organic loading in natural water using spectral fluorescent signatures.

Spectral fluorescent signature (SFS) is a rapid, reagent free and inexpensive technique, which has great potential for environmental monitoring of aqueous systems, especially for predicting dissolved organic carbon (DOC) along natural waters. This technical note aimed to examine the possibility to use SFS associated with partial least squares regression (PLS) to assess the organic loading in natural water. A model was built using samples of water collected between October 1999 and February 2002 on the Passaic River at Little Falls, NJ, USA. A correlation was established between measured DOC, SFS, and the corresponding daily registered flow from United States Geological Survey (USGS) New Jersey's streamflow database. The methodology presented herein looks promising in making use of the significant organic characteristics information contained in a SFS for application and use in spatial and temporal water quality management and treatment.

Environmental Monitoring↗

Hydrocarbon circulation and colonial signature in Pachycondyla villosa.

In ants, both cuticular and postpharyngeal gland (PPG) hydrocarbons (HCs) have been involved in nestmate recognition. However, no detailed comparison is available. A comparative study including also high density lipophorin (HDLp), an internal HC carrier, was therefore undertaken on Pachycondyla villosa. Purified HDLp is an 820 kDa lipoprotein with a density of 1.114 g/ml and two 245 and 80 kDa apo-proteins. Its hydrocarbon profile is very similar with the cuticular one, in agreement with its hydrocarbon carrier function. Conversely, n-alkanes and externally branched monomethylalkanes are markedly decreased in the PPG. According to their physical properties, this suggests that they are involved in waterproofing on the cuticle. The PPG actually contains only internally branched mono-, dimethylalkanes or monomethylalkenes; their greater fluidity is more adequate for chemical communication. The percentages of some of them are statistically not different between the cuticle and PPG. Their mixtures vary with colonies and they may thus be involved in colonial signature. A scheme for hydrocarbon circulation is discussed, involving lipophorin, cuticle, PPG and self-grooming in one individual, a pathway complementary or alternative to the selective delivery by lipophorin in some other insects. HCs are then distributed between nestmates' cuticles through allo-grooming and physical contacts.

Animals↗

The cytokine signature of MOG-specific CD4 cells in the EAE of C57BL/6 mice.

Experimental allergic encephalomyelitis (EAE) is an animal model of multiple sclerosis. While EAE is mediated by the cytokines produced by specific T cells, the cytokine signature of these effector cells is unresolved. We tested CD4 cells from MOG peptide 35-55 immunized C57BL/6 mice for their peptide induced cytokine production on antigen presenting cells of the respective cytokine knockout mice, or wild type mice. IL-4 and IL-6 production was seen on wild type antigen presenting cells, suggesting that IL-4 and IL-6 are not T cell products. In contrast, IFN-gamma, IL-2 and IL-3 were found to be produced by the MOG specific CD4 cells. Understanding the cognate vs. bystander cytokine production in EAE might help dissect the contribution of cytokines to the pathogenesis of the disease.

Animals↗

Tibial cancellous bone changes in patients with knee osteoarthritis. A short-term longitudinal study using Fractal Signature Analysis.

OBJECTIVE: To quantify tibial cancellous bone changes over 24 months in patients with medial compartment knee osteoarthritis (OA) subdivided into those with slow or detectable joint space narrowing (JSN). METHOD: Digitised macroradiographs (4x) were obtained at baseline and 24 months from 40 patients (F:26) and subdivided by computerised measurement of minimum medial compartment joint space width (JSW) into those with slow JSN (<0.2 mm/year, n=66) or detectable JSN (>or=0.2 mm/year, n=14) and who had a mean (range) JSW at baseline of 3.89 (1.66-5.48) mm and 3.73 (2.49-5.74) mm, respectively. Fractal Signature Analysis measured longitudinal change in bone structure at four regions of interest (ROI): medial and lateral subchondral (Sc) and subarticular (Sa) regions. RESULTS: Mean (range) JSN for slow and detectable groups was 0.01 (-0.31-0.18) mm/year and 0.44 (0.20-1.01)mm/year, respectively. All ROIs in both groups had significant (P<0.05) decrease in fractal dimension (FD) at most trabecular sizes (vertical: 0.36-1.14 mm; horizontal: 0.36-1.14 mm, excluding the lateral Sa region) over 24 months. There were no between-group differences except at a few trabecular sizes within the Sa regions where the detectable JSN group had significantly (P<0.05) greater decrease in FD compared to the slow JSN group (medial: horizontal sizes 0.54-0.72 mm, 1.02-1.08 mm; lateral: vertical sizes 0.90-1.02 mm). CONCLUSION: Bone loss occurred in all knees with medial compartment OA. Decrease in FD of vertical and horizontal trabeculae was consistent with decrease in trabecular number associated with loss. The pattern of bone loss was similar in knees with slow and detectable JSN.

Aged↗

Cancellous bone changes in hip osteoarthritis: a short-term longitudinal study using fractal signature analysis.

OBJECTIVE: To quantify changes to the trabecular structure in the femoral heads of patients with hip osteoarthritis (OA). METHODS: Patients with OA (n=14; F=7), mean (standard deviation age) 50.6 (10.1) years, had macroradiographs at approximately x4 magnification at baseline and 18 months later using a standardized protocol. Following digitization, computerized measurement was obtained of minimum hip joint space width and fractal signature analysis (FSA) measured longitudinal changes separately in the principal compressive (vertical) and horizontal trabeculae at the region of interest within the centre of the head. RESULTS: The patient group had mean annual rate of joint space narrowing of 0.14+/-0.36 mm/yr. FSA detected no significant changes in horizontal trabeculae, whereas the larger principal compressive (vertical) trabeculae (0.96 mm to 1.02 mm) increased significantly in thickness and the fine to medium trabeculae (0.18 mm to 0.54 mm) decreased significantly in number. CONCLUSION: The increased thickness of the larger trabeculae within the compressive structural element of the femoral head is a response to the increase in stress associated with an overall loss of trabeculae in this region, suggesting the presence of an osteoporosis within the femoral head in OA patients.

Female↗

SIGNATURE: a single-particle selection system for molecular electron microscopy.

SIGNATURE is a particle selection system for molecular electron microscopy. It applies a hierarchical screening procedure to identify molecular particles in EM micrographs. The user interface of the program provides versatile functions to facilitate image data visualization, particle annotation and particle quality inspection. The system design emphasizes both functionality and usability. This software has been released to the EM community and has been successfully applied to macromolecular structural analyses.

Algorithms↗