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At least 937 records · Page 52Linked to original sources
PubMed2004

Short consensus probes with 3'-minor groove binder of the immunoglobulin heavy-chain gene for real-time quantitative PCR in B-cell non-Hodgkin lymphomas.

We used 3'-minor groove binder (MGB) technology to develop consensus fluorogenically labeled probes of the immunoglobulin heavy-chain (IgH) gene for detecting minimal residual disease (MRD) in B-cell non-Hodgkin lymphoma (B-NHL). Sequence data from 59 patients with B-NHLs revealed a narrow consensus region as a result of somatic hypermutations and variable VH usage, indicating that it would be difficult to design ordinary non-MGB probes. MGB probes, characterized by shorter length but higher melting temperature, are more suitable for this situation than ordinary non-MGB probes. In fact, the present data indicated that about 20% more cases were detectable with MGB probes (34/59, 57.6%) than with the non-MGB probes (23/59, 39.0%) designed by Donovan et al. MGB technology is useful for the design of consensus fluorogenically labeled probes of the IgH gene for detecting MRD.

Base Sequence↗
PubMed2006

Determination of the consensus DNA-binding sequence and a transcriptional activation domain for ESE-2.

The ESE (epithelium-specific Ets) subfamily of Ets transcription factors plays an important role in regulating gene expression in a variety of epithelial cell types. Although ESE proteins have been shown to bind to regulatory elements of some epithelial genes, the optimal DNA-binding sequence has not been experimentally ascertained for any member of the ESE subfamily of transcription factors. This has made the identification and validation of their targets difficult. We are studying ESE-2 (Elf5), which is highly expressed in epithelial cells of many tissues including skin keratinocytes. Here, we identify the preferred DNA-binding site of ESE-2 by performing CASTing (cyclic amplification and selection of targets) experiments. Our analysis shows that the optimal ESE-2 consensus motif consists of a GGA core and an AT-rich 5'- and 3'-flanking sequences. Mutational and competition experiments demonstrate that the flanking sequences that confer high DNA-binding affinity for ESE-2 show considerable differences from the known consensus DNA-binding sites of other Ets proteins, thus reinforcing the idea that the flanking sequences may impart recognition specificity for Ets proteins. In addition, we have identified a novel isoform of murine ESE-2, ESE-2L, that is generated by use of a hitherto unreported new exon and an alternate promoter. Interestingly, transient transfection assays with an optimal ESE-2 responsive reporter show that both ESE-2 and ESE-2L are weak transactivators. However, similar studies utilizing GAL4 chimaeras of ESE-2 demonstrate that while the DNA-binding ETS (E twenty-six) domain functions as a repressor, the PNT (pointed domain) of ESE-2 can act as a potent transcriptional activation domain. This novel transactivating property of PNT is also shared by ESE-3, another ESE family member. Identification of the ESE-2 consensus site and characterization of the transcriptional activation properties of ESE-2 shed new light on its potential as a regulator of target genes.

Adaptor Proteins, Vesicular Transport↗
PubMed1984

A procedure for phonetic transcription by consensus.

A consensus transcription procedure is presented, and representative data are reported. The procedure includes explicit response definitions for mapping narrow phonetic transcription onto dichotomous, nonerror/error scores and 17 rules for obtaining consensus between two transcribers. The data include descriptive statistics for consensus rule use based on over 18,000 sounds transcribed during a normative study of speech sound acquisition in children aged 3-6 years. Validity and reliability issues in phonetic transcription are discussed.

Child↗
PubMed1999

Bovine chromosome 4 workshop: consensus and comprehensive linkage maps.

The report of the bovine chromosome 4 (BTA4) workshop is presented. Six laboratories contributed a total of 30,168 informative meioses from 62 loci. Twenty-two loci were typed by at least two independent laboratories and were used to construct a consensus linkage map of BTA4. The remaining 40 loci were subsequently incorporated into a comprehensive map. The sex-averaged consensus map covered 131.4 cM. The female map was 124.3 cM in length, while the male map was 134.3 cM. The comprehensive sex-averaged map spanned 141.6 cM. The length of the female and male comprehensive maps were 123.1 cM and 156.4 cM, respectively. Average genetic distance between loci was 6 and 2.3 cM for the consensus and comprehensive linkage maps, respectively.

Animals↗
PubMed2000

Endodontic retreatment decisions: no consensus.

AIM: The objectives of the present study were to: (i) evaluate the consensus, if any, amongst dental schools, students and their instructors managing the same clinical cases, all of which involved endodontically treated teeth; and (ii) determine the predominant proposed treatment option. METHODOLOGY: Final year students, endodontic staff members and instructors of 10 European dental schools were surveyed as decision makers. Fourteen different radiographic cases of root canal treated teeth accompanied by a short clinical history were presented to them in a uniform format. For each case the decision makers were requested to: (i) choose only one out of nine treatment alternatives proposed, from 'no treatment' to 'extraction' via 'retreatment' and 'surgery' (ii) assess on two 5-point scales: the difficulty of making a decision, and the technical complexity of the retreatment procedure. RESULTS: The results indicate wide inter- and also intra-school disagreements in the clinical management of root canal treated teeth. Analysis of variance showed that the main source of variation was the 'school effect', explaining 1.8% (NS) to 18.6% (P < 0.0001) of the treatment variations. No other factor explained as much variance. Decision difficulty was moderately correlated to technical complexity (Pearsons' r ranging from 0.19 to 0.35, P < 0.0001). CONCLUSIONS: No clear consensus occurred amongst and within dental schools concerning the clinical management of the 14 cases. The lack of consensus amongst schools seems to be due mainly to chance or uncertainty, but can be partly explained by the 'school effect'.

Analysis of Variance↗
PubMed2000

Randomized controlled trials and consensus as a basis for interventions in internal medicine.

OBJECTIVES: To estimate the proportion of routine clinical interventions in internal medicine that are supported by the results of randomized controlled trials or consensus amongst experienced internists. DESIGN: Retrospective review of case records allowed one or more major diagnosis-intervention combination(s) to be identified for each patient. The scientific literature was searched for metaanalyses and randomized controlled trials in electronic databases that supported the specific intervention used. When support from randomized trials was lacking, possible consensus on management was sought by asking national expert panels of experienced clinicians. SETTING: Department of Medicine at a Swedish teaching hospital. SUBJECTS: At total of 197 consecutively admitted medical inpatients. RESULTS: Fifty per cent of the diagnosis-intervention combinations (186/369) were supported by results from randomized controlled trial evidence and 34% (125/369) were supported by consensus amongst experienced clinicians. The proportion of interventions based on randomised controlled trials was highest in patients with cardiac (64%) and other circulatory diagnoses (73%). There were no important differences between sexes or between age groups. CONCLUSIONS: Half of the interventions used in routine clinical practice amongst medical inpatients are supported by results from randomized controlled trials. These results refute popular claims that only a small proportion of medical interventions are supported by scientific evidence.

Aged↗
PubMed2004

Difference and consensus of whole cell Salmonella enterica subsp. enterica serovars matrix-assisted laser desorption/ionization time-of-flight mass spectrometry spectra.

AIM: Application of MALDI-TOF MS for characterization of strains of Salmonella enterica subsp. enterica. METHODS AND RESULTS: Whole cells were analysed by MALDI-TOF MS. Spectra with a maximum of 500 mass peaks between (m/z) 0 and 25000 were examined for consensus peaks manually and by a computer software algorithm. Consensus peaks were observed by both methods for spectra of Salmonella enterica serovars Derby, Hadar, Virchow, Anatum, Typhimurium and Enteritidis. CONCLUSIONS: Differences in numbers of consensus peaks in spectra obtained by manual and computer comparison indicated that development of the software involving statistical analysis of peak accuracy is necessary. SIGNIFICANCE AND IMPACT OF THE STUDY: Development of an analysis system for peak profiles in whole cell MALDI-TOF MS spectra to enable intra and interlaboratory comparison.

Bacteriophage Typing↗
PubMed2002

Bypass or angioplasty for severe limb ischaemia? A Delphi Consensus Study.

OBJECTIVES: To examine the level of agreement among vascular surgeons and interventional radiologists regarding their preference for the surgical or endovascular management of severe limb ischaemia. DESIGN: Delphi consensus study using 596 different hypothetical patient scenarios. PARTICIPANTS: Delphi consensus group for the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial. METHODS: Twenty consultant vascular surgeons and 17 interventional radiologists completed both rounds of the study. The scenarios detailed the anatomical extent of disease, whether the patients had rest pain only or had tissue loss, and whether or not a suitable vein for bypass was available. Panellists were asked to score their treatment preference for either surgery or angioplasty on an eight-point scale. Outliers (top 10% and bottom 10% responses) were removed. If the remaining 80% of responses fell within a 3-point range, this was defined as "agreement". If they did not, this was considered "disagreement". RESULTS: There was substantial disagreement in 484 (81%) of scenarios in round 1 and 401 (67%) in round 2. This disagreement was greater among surgeon than radiologists in both round 1 (83 vs 65%) and round 2 (69 vs 42%). Surgeons also demonstrated less convergence between rounds. CONCLUSIONS: There is substantial disagreement between and among surgeons and radiologists with regard to the appropriateness of surgery or angioplasty for severe limb ischaemia. This lack of consensus stems from the absence of an evidence base and means that the same patient may receive entirely different treatment depending on which hospital and consultant they attend. Not only may this unexplained variation be clinically unsatisfactory, it has major implications for the planning and use of health service resources.

Angioplasty, Balloon↗
PubMed2001

An approach to consensus building using the Delphi technique: developing a learning resource in mental health.

Health service research is best served through the collaboration of researchers and practitioners. This study utilizes a multi-method approach in developing a learning resource in clinical risk management in mental health. Phase one of the project is reported here; using a Delphi Technique to build the learning resource. Using the Delphi enabled a group of 'experts' to explore a complex issue and move towards consensus. In addition, the Delphi technique enabled the researchers to repeatedly access a dispersed group of 'experts' in an economic way. A three round Delphi was undertaken and results were analyzed (medians, means, standard deviations and thematic content analysis) to facilitate consensus building from a range of perspectives. The analytical model chosen is discussed in the context of prior use of the Delphi as a consensus building technique. The researchers conclude that analysis using medians and means to measure the level of agreement/disagreement with the content and structure of the learning pack, standard deviations to measure 'tightening' of the group view and Thematic Content Analysis of qualitative data was an effective approach. They argue that in the education and health fields, group views are particularly important and that this is a central tenet of the Delphi.

Delphi Technique↗
PubMed2003

Designed to be stable: crystal structure of a consensus ankyrin repeat protein.

Ankyrin repeat (AR) proteins mediate innumerable protein-protein interactions in virtually all phyla. This finding suggested the use of AR proteins as designed binding molecules. Based on sequence and structural analyses, we designed a consensus AR with fixed framework and randomized interacting residues. We generated several combinatorial libraries of AR proteins consisting of defined numbers of this repeat. Randomly chosen library members are expressed in soluble form in the cytoplasm of Escherichia coli constituting up to 30% of total cellular protein and show high thermodynamic stability. We determined the crystal structure of one of those library members to 2.0-A resolution, providing insight into the consensus AR fold. Besides the highly complementary hydrophobic repeat-repeat interfaces and the absence of structural irregularities in the consensus AR protein, the regular and extended hydrogen bond networks in the beta-turn and loop regions are noteworthy. Furthermore, all residues found in the turn region of the Ramachandran plot are glycines. Many of these features also occur in natural AR proteins, but not in this rigorous and standardized fashion. We conclude that the AR domain fold is an intrinsically very stable and well-expressed scaffold, able to display randomized interacting residues. This scaffold represents an excellent basis for the design of novel binding molecules.

Amino Acid Sequence↗
PubMed1983

Chromosomal replication origin from the marine bacterium Vibrio harveyi functions in Escherichia coli: oriC consensus sequence.

The chromosomal replication origin (oriC) of Vibrio harveyi has been isolated on a plasmid and shown to function as an origin in Escherichia coli. The nucleotide sequence of the V. harveyi oriC was determined. From a comparison of this sequence with oriC sequences of five enteric bacteria, we derived a consensus sequence of bacterial origins that function in E. coli. This consensus sequence identifies 122 positions within oriC where nucleotide substitutions can occur without loss of origin function. These positions are clustered rather than scattered. Four interrelated nine-base-pair repeats and eight of the dam methylation G-A-T-C sites are conserved in the consensus sequence. Very few relative insertion-deletion changes occur, and these are localized to one region of oriC. The genes for three polypeptides linked to the V. harveyi oriC were identified by using in vitro protein synthesis directed by deletion derivative plasmid templates. One of these genes, coding for a 58,000 Mr polypeptide and located 3.0 kilobase pairs from the V. harveyi oriC region, is lethal to E. coli when many copies (approximately 40 per cell) are present (high copy lethal or HCL gene). In addition, nucleotide sequence analysis showed that a different gene, the gid gene to the left of oriC, is highly conserved between E. coli and V. harveyi, whereas the coding region to the right of oriC is much less conserved.

Base Sequence↗
PubMed1983

Promoters regulated by the glnG (ntrC) and nifA gene products share a heptameric consensus sequence in the -15 region.

We have determined the nucleotide sequences of the Klebsiella pneumoniae nifL (regulation of N2 fixation genes) and the Escherichia coli glnA (glutamine synthetase) promoters. We compared these sequences with the published sequences of three other promoters that, like the nifL and glnA promoters, are activated by the general nitrogen regulators glnF (ntrA) and glnG (ntrC). The three promoters are the argTr (arginine transport) and dhuA (histidine transport) promoters of Salmonella typhimurium and the nifH (nitrogenase) promoter of Rhizobium meliloti. All five sequences (with at most one mismatch) contain the heptameric consensus sequence T-T-T-T-G-C-A. In the R. meliloti nifH and K. pneumoniae nifL promoters, in which the transcription initiation sites have been determined, the consensus sequence is situated in the -15 region. We recently reported that the K. pneumoniae nifA product, which activates nif genes, can substitute for the glnG (ntrC) product in activating promoters of several genes involved in nitrogen assimilation, including the nifL, the glnA, and the R. meliloti nifH promoters. It is likely that nifA also activates the S. typhimurium argTr and dhuA promoters. In contrast, the glnG product cannot substitute for the nifA product in the activation of the K. pneumoniae nifH (nitrogenase) promoter. Consistent with this latter observation, and supporting the conclusion that the T-T-T-T-G-C-A sequence is a regulatory site for glnG product activation, the K. pneumoniae nifH promoter (C-C-C-T-G-C-A) has only partial similarity with the T-T-T-T-G-C-A consensus sequence in the -15 region.

Amino Acid Sequence↗
PubMed1985

Consensus sequence for Escherichia coli heat shock gene promoters.

We have identified promoters for the Escherichia coli heat shock operons dnaK and groE and the gene encoding heat shock protein C62.5. Transcription from each promoter is heat-inducible in vivo, and each is recognized in vitro by RNA polymerase containing sigma 32, the sigma factor encoded by rpoH (htpR) but not by RNA polymerase containing sigma 70. We compared the sequences of the heat shock promoters and propose a consensus promoter sequence, having T-N-t-C-N-C-c-C-T-T-G-A-A in the -35 region and C-C-C-C-A-T-t-T-a in the -10 region. These sequences differ from the consensus sequence recognized by holoenzyme containing sigma 70, the major sigma in E. coli. We suggest that the accumulated consensus sequences of promoters recognized by alternate forms of holoenzyme are compatible with a model in which sigma recognizes only the -10 region of the promoter.

Base Sequence↗
PubMed1987

Efficient Tn10 transposition into a DNA insertion hot spot in vivo requires the 5-methyl groups of symmetrically disposed thymines within the hot-spot consensus sequence.

Transposon Tn10 inserts preferentially at particular insertion "hot spots" that share a symmetrical 6-base-pair consensus sequence: 5' GCTNAGC 3'. The protein that recognizes this sequence is not known but is likely to be the Tn10-encoded transposase protein. We present evidence that the 5-methyl groups of the two thymines in this sequence are essential for efficient transposon insertion; in their absence the sequence is still recognized, but at lower efficiency. We have reached this conclusion by examination of a specific hot spot whose sequence is 5' GCCAGGC 3'. The innermost cytosines of this sequence happen to be substrates for methylation at their 5 positions by the bacterial dcm-encoded methylase. We find that Tn10 transposes into this site 15 times more frequently in a Dcm+ host than in a Dcm- host; in the Dcm- host, insertions still occur, but at a low frequency. Thus, at this site, the absence of pyrimidine 5-methyl groups at the third positions of the consensus sequence is sufficient to convert a strong insertion hot spot into a weaker but still recognizable hot spot. This observation supports the general proposition, suggested previously by comparisons among consensus sequences, that the presence or absence of these 5-methyl groups is one major feature that can make the difference between a strong and a weak Tn10 insertion hot spot.

Base Sequence↗
PubMed2000

PU.1 and interferon consensus sequence-binding protein regulate the myeloid expression of the human Toll-like receptor 4 gene.

The protein product of the Toll-like receptor (TLR) 4 gene has been implicated in the signal transduction events induced by lipopolysaccharide (LPS). In mice, destructive mutations of Tlr4 impede the normal response to LPS and cause a high susceptibility to Gram-negative infection. Expression of TLR4 mRNA in humans is restricted to a small number of cell types, including LPS-responsive myeloid cells, B-cells, and endothelial cells. To investigate the molecular basis for TLR4 expression in cells of myeloid origin, we cloned the human TLR4 gene and analyzed its putative 5'-proximal promoter. In transient transfections a region of only 75 base pairs upstream of the major transcription initiation site was sufficient to induce maximal luciferase activity in THP-1 cells. The sequence of this region is similar in human and mouse TLR4 genes and lacks a TATA box, typical Sp1-sites or CCAAT box sequences. Instead, it contains consensus-binding sites for Ets family transcription factors, octamer-binding factors, and a composite interferon response factor/Ets motif. The activity of the promoter in macrophages was strictly dependent on the integrity of both half sites of the composite interferon response factor/Ets motif, which was constitutively bound by the myeloid and B-cell-specific transcription factor PU.1 and interferon consensus sequence-binding protein. These results indicate that the two tissue-restricted transcription factors PU.1 and interferon consensus sequence-binding protein participate in the basal regulation of human TLR4 in myeloid cells. Cloning of the human TLR4 gene provides a basis for further investigation of the possible impact of genetic variations on the susceptibility to infection and sepsis.

Amino Acid Sequence↗
PubMed2000

Consensus and variant cAMP-regulated enhancers have distinct CREB-binding properties.

Recent determination of the cAMP response element-binding protein (CREB) basic leucine zipper (bZIP) consensus CRE crystal structure revealed key dimerization and DNA binding features that are conserved among members of the CREB/CREM/ATF-1 family of transcription factors. Dimerization appeared to be mediated by a Tyr(307)-Glu(312) interhelical hydrogen bond and a Glu(319)-Arg(314) electrostatic interaction. An unexpected hexahydrated Mg(2+) ion was centered above the CRE in the dimer cavity. In the present study, we related these features to CREB dimerization and DNA binding. A Y307F substitution reduced dimer stability and DNA binding affinity, whereas a Y307R mutation produced a stabilizing effect. Mutation of Glu(319) to Ala or Lys attenuated dimerization and DNA binding. Mg(2+) ions enhanced the binding affinity of wild-type CREB to the palindromic CRE by approximately 20-fold but did not do so for divergent CREs. Similarly, mutation of Lys(304), which mediates the CREB interaction with the hydrated Mg(2+), blocked CREB binding to the palindromic but not the variant CRE sequences. The distinct binding characteristics of the K304A mutants to the consensus and variant CRE sequences indicate that CREB binding to these elements is differentially regulated by Mg(2+) ions. We suggest that CREB binds the consensus and variant CRE sequences through fundamentally distinct mechanisms.

Base Sequence↗
PubMed2001

NMR spectroscopy reveals the solution dimerization interface of p53 core domains bound to their consensus DNA.

The p53 protein is a transcription factor that acts as the major tumor suppressor in mammals. The core DNA-binding domain is mutated in about 50% of all human tumors. The crystal structure of the core domain in complex with DNA illustrated how a single core domain specifically interacts with its DNA consensus site and how it is inactivated by mutation. However, no structural information for the tetrameric full-length p53-DNA complex is available. Here, we present novel experimental insight into the dimerization of two p53 core domains upon cooperative binding to consensus DNA in solution obtained by NMR. The NMR data show that the p53 core domain itself does not appear to undergo major conformational changes upon addition of DNA and elucidate the dimerization interface between two DNA-bound core domains, which includes the short H1 helix. A NMR-based model for the dimeric p53 core-DNA complex incorporates these data and allows the conclusion that the dimerization interface also forms the actual interface in the tetrameric p53-DNA complex. The significance of this interface is further corroborated by the finding that hot spot mutations map to the H1 helix, and by the binding of the putative p53 inhibitor 53BP2 to this region via one of its ankyrin repeats. Based on symmetry considerations it is proposed that tetrameric p53 might link non-contiguous DNA consensus sites in a sandwich-like manner generating DNA loops as observed for transcriptionally active p53 complexes.

Amino Acid Sequence↗
PubMed2002

The epithelial mitogen keratinocyte growth factor binds to collagens via the consensus sequence glycine-proline-hydroxyproline.

The binding of certain growth factors and cytokines to components of the extracellular matrix can regulate their local availability and modulate their biological activities. We show that mesenchymal cell-derived keratinocyte growth factor (KGF), a key stimulator of epithelial cell proliferation during wound healing, preferentially binds to collagens I, III, and VI. Binding is inhibited in a dose-dependent manner by denatured single collagen chains and collagen cyanogen bromide peptides. This interaction is saturable with dissociation constants of approximately 10(-8) to 10(-9) m and estimated molar ratios of up to three molecules of KGF bound to one molecule of triple helical collagen. Furthermore, collagen-bound KGF stimulated the proliferation of transformed keratinocyte or HaCaT cells. Ligand blotting of collagen-derived peptides points to a limited set of collagenous consensus sequences that bind KGF. By using synthetic collagen peptides, we defined the consensus sequence (Gly-Pro-Hyp)(n) as the collagen binding motif. We conclude that the preferential binding of KGF to the abundant collagens leads to a spatial pattern of bioavailable KGF that is dictated by the local organization of the collagenous extracellular matrix. The defined collagenous consensus peptide or its analogue may be useful in wound healing by increasing KGF bioactivity and thus modulating local epithelial remodeling and regeneration.

Amino Acid Motifs↗