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At least 1,045 records · Page 58Linked to original sources
PubMed2001

The K+ channel signature sequence of murine Kir2.1: mutations that affect microscopic gating but not ionic selectivity.

1. We have studied the effects on ionic selectivity and gating of Kir2.1 of replacing Tyr (Y) in the GYG signature sequence with Phe (Y145F), Leu (Y145L), Met (Y145M), Ala (Y145A) or Val (Y145V). 2. The mutant Y145F showed no changes in ionic selectivity (as indicated by the permeability coefficient ratios PNa/PK or PRb/PK), indicating that a hydrogen bond between Tyr and other residues is not essential for K+ selectivity. Y145L, Y145M, Y145A and Y145V did not express as monomers. 3. None of the channels made from covalently linked tandem dimers with wild-type and mutant subunits (WT-mutant) had altered ionic selectivity (PNa/PK or PRb/PK), indicating that 4-fold symmetry is not required. 4. Macroscopic currents activated under hyperpolarization and the time constants for activation were reduced e-fold per 23 mV hyperpolarization in wild-type. This gating, believed to be due to the release of polyamines from the pore, was little affected by mutation of Y14. There was similarly little effect on the relationship between chord conductance (gK) and membrane potential. 5. Unitary conductance (140 mM [K+]o) was also little affected by mutation and was reduced only in channels formed from WT-Y145M, from 22.7 +/- 0.4 pS (n = 5) in wild-type to 17.1 +/- 0.5 pS (n = 4) in WT-Y145M. 6. Steady-state recording of unitary currents showed that channel open times were affected by the residue that replaced Tyr in GYG. Channel openings were particularly brief in WT-Y145V, where the mean open time was reduced from 102 ms at -120 mV in wild-type to 6 ms in WT-Y145V. 7. Thus in Kir2.1, GFG can act as a K+ selectivity filter, as can G(L/M/A/V)G, at least in dimers also containing GYG. Channel open time duration depended on the residue at position 145, consistent with the H5 region helping to determine the dwell time of the channel in the open state.

Algorithms↗
PubMedDate not supplied

Expression profile of ovarian tumors: distinct signature of Sertoli-Leydig cell tumor.

Epithelial ovarian tumors are the most common subtype of ovarian cancer. In this study, we reveal distinct expression signatures of previously uncharacterized ovarian carcinoma subtypes, including endometrioid component of mixed ovarian tumor and Sertoli-Leydig tumor. Both subtypes were compared to the most common and well-characterized ovarian epithelial carcinoma of the serous type. These comparisons were performed by complementaryDNA (cDNA) microarrays allowing high-fidelity measurements of the expression levels of 39,360 human individual cDNA species representing both known and unknown human genes. Functional analysis of differentially expressed genes in Sertoli-Leydig tumor revealed an upregulation in sonic hedgehog pathway, deregulation of several metabolic pathways especially in amino acid metabolism and overexpression of genes associated with protein synthesis, including ribosomal genes.

Female↗
PubMedDate not supplied

[14C]2-deoxyglucose autoradiographic technique provides a metabolic signature of cobalt-induced focal epileptogenesis.

Brain glucose consumption in rats with unilateral visual cortex implants of epileptogenic cobalt rods was assessed by the 2-deoxyglucose (2-DG) method. Nine days postoperatively, "dark patches" of higher 2-DG uptake, bordered by tissue showing lesser uptake, were observed around the implant site. The dark patches were located just beyond the damaged perifocal zone, in normal-appearing Nissl-stained cortex designated by the electrocorticographic (ECoG) work of other investigators as the focus of epileptic activity. As was also predictable from earlier research, the cortical patches were prominent on day 9 and absent by day 35. Regions of high metabolic activity in thalamus, presumably the result of axonal transport of cobalt ions, were also strikingly evident in the projection nuclei connecting with the cortical implant sites. The abnormal thalamic activity is likely the metabolic counterpart of "secondary foci," a characteristic feature of the cobalt model. The longevity of these thalamic dark patches, which developed between days 2 and 9 and did not disappear until between days 90 and approximately 365, may account for the persistent sensitivity to seizure-inducing drugs that occurs secondary to cobalt implants. The absence of dark patches after control nonseizure-inducing but toxic copper implants argued against the possibility that the dark patches reflected some nonepileptogenic effect of the cobalt. As well, under pentobarbital anesthesia, the patches behaved in a manner suggesting that their 2-DG uptake reflected neural and not glial cell activity. Dark patches are a distinctive autoradiograph signature of tissue made epileptic by cobalt.

Animals↗
PubMed2004

A multicenter clinical evaluation of the Clot Signature Analyzer.

BACKGROUND: The Clot Signature Analyzer (CSA) was designed to assess global hemostasis as a screening assay using non-anticoagulated whole blood. Three different measurements are produced by the instrument: platelet hemostasis time (PHT), clot time (CT), and collagen-induced thrombus formation (CITF). OBJECTIVES: The purpose of the present study was to determine normal ranges for these measurements and assess the performance of the CSA in patients with well-characterized hemostatic disorders and in normal subjects. PATIENTS AND METHODS: Four institutions participated in the study. Each established their own normal reference ranges. Patients with well-characterized hemostatic disorders and concurrent normal controls were subsequently examined. RESULTS: Normal ranges between institutions were similar although statistically different. One hundred and eight patients were examined: 46 individuals with von Willebrand disease (VWD) (type 1, 26; type 2A, 11; type 2B, six; type 3, three); 38 patients with a coagulation factor deficiency; 13 individuals with platelet function defects; 10 patients taking warfarin; and one individual on low-molecular-weight heparin. Of these patients, 89% had at least one abnormality by CSA: 42/46 VWD patients, 35/38 coagulation protein defect patients, 9/13 patients with platelet function defects, 9/10 patients on warfarin and 1/1 patient on low-molecular-weight heparin. Of 116 normal subjects, 103 (89%) fell within the centers' normal range. These data suggest that the CSA has a good sensitivity for bleeding disorders.

Adult↗
PubMedDate not supplied

A three nucleotide signature sequence in small subunit rRNA divides human Giardia in two different genotypes.

The nucleotide sequence of the 16S rRNA gene and the space DNA region was determined for Giardia duodenalis, obtained from humans in The Netherlands (AMC-4) and Washington State (CM). These rDNA sequences differ from other G. duodenalis isolates (Portland-1 and BRIS/83/HEPU/ 106) both of which have virtually identical rDNA sequences. The most characteristic feature was found close to the 5' end of the 16S rRNA. The Portland-1 -Bris/83/HEPU/ 106 type has GCG in position 22-24, while AMC-4 and CM have AUC in this position. These two sequences, present in an otherwise conserved region of the 16S rRNA, are "signature" sequences, which divide Giardia isolates into two different groups.

Animals↗
PubMed1993

Microbial hydrogenases: primary structure, classification, signatures and phylogeny.

Thirty sequenced microbial hydrogenases are classified into six classes according to sequence homologies, metal content and physiological function. The first class contains nine H2-uptake membrane-bound NiFe-hydrogenases from eight aerobic, facultative anaerobic and anaerobic bacteria. The second comprises four periplasmic and two membrane-bound H2-uptake NiFe(Se)-hydrogenases from sulphate-reducing bacteria. The third consists of four periplasmic Fe-hydrogenases from strict anaerobic bacteria. The fourth contains eight methyl-viologen- (MV), factor F420- (F420) or NAD-reducing soluble hydrogenases from methanobacteria and Alcaligenes eutrophusH16. The fifth is the H2-producing labile hydrogenase isoenzyme 3 of Escherichia coli. The sixth class contains two soluble tritium-exchange hydrogenases of cyanobacteria. The results of sequence comparison reveal that the 30 hydrogenases have evolved from at least three different ancestors. While those of class I, II, IV and V hydrogenases are homologous, i.e. sharing the same evolutionary origin, both class III and VI hydrogenases are neither related to each other nor to the other classes. Sequence comparison scores, hierarchical cluster structures and phylogenetic trees show that class II falls into two distinct clusters composed of NiFe- and NiFeSe-hydrogenases, respectively. These results also reveal that class IV comprises three distinct clusters: MV-reducing, F420-reducing and NAD-reducing hydrogenases. Specific signatures of the six classes of hydrogenases as well as some subclusters have been detected. Analyses of motif compositions indicate that all hydrogenases, except those of class VI, must contain some common motifs probably participating in the formation of hydrogen activation domains and electron transfer domains. The regions of hydrogen activation domains are highly conserved and can be divided into two categories. One corresponds to the 'nickel active center' of NiFe(Se)-hydrogenases. It consists of two possible specific nickel-binding motifs, RxCGxCxxxH and DPCxxCxxH, located at the N- and C-termini of so-called large subunits in the dimeric hydrogenases, respectively. The other is the H-cluster of the Fe-hydrogenases. It might comprise three motifs on the C-terminal half of the large subunits. However, the motifs corresponding to the putative electron transfer domains, as well as their polypeptides chains, are poorly or even not at all conserved. They are present essentially on the small subunits in NiFe-hydrogenases. Some of these motifs resemble the typical ferredoxin-like Fe-S cluster binding site.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1996

Sequence signatures from DNA amplification fingerprints reveal fine population structure of the dogwood pathogen Discula destructiva.

Isolates of Discula destructiva Redlin and an undescribed species of Discula, the filamentous fungi that cause anthracnose of flowering (Cornus florida L.) and Pacific (Cornus nuttalli Aud.) dogwoods, were analyzed for genetic variation by nucleic acid scanning with arbitrary mini-hairpin oligonucleotide primers. While the fungal population was highly homogeneous throughout the disease range in eastern and western North America, the generation of arbitrary signatures from amplification profiles (ASAP) distinguished isolates from the northeast, middle and southern Appalachian mountain range, and western United States and Canada. ASAP involves a dual-step arbitrary primer-based amplification procedure that generates a large number of informative allelic characters by amplification of monomorphic DNA fingerprints. ASAP analyses showed a fine fungal population structure consistent with the recent and separate introduction of the pathogen on the west and east coasts of North America.

Algorithms↗
PubMed1999

Signature region within the 16S rDNA sequences of Aeromonas popoffii.

To identify a group of eight Aeromonas strains of our collection showing ribotyping patterns similar to those described for the species Aeromonas popoffii, 16S rRNA gene sequence analysis was performed. Results were in agreement with the DNA binding values, and allowed the identification of a 'signature region' differentiating the A. popoffii strains from all other members of the genus Aeromonas.

Aeromonas↗
PubMed2001

Adaptation of signature-tagged mutagenesis to Escherichia coli K1 and the infant-rat model of invasive disease.

With the exception of the polysialic acid capsule (K1 antigen), little is known about other virulence factors needed for systemic infection by Escherichia coli K1, the leading cause of Gram-negative neonatal meningitis in humans. In this work, the functional genomics method of signature-tagged mutagenesis (STM) was adapted to E. coli K1 and the infant-rat model to identify non-capsule virulence genes. Validation of the method was demonstrated by the failure to recover a reconstructed acapsular mutant from bacterial pools used to systemically infect 5-day-old rats. Three new genes required for systemic disease were identified from a total of 192 mutants screened by STM (1.56% hit rate). Gut colonization, Southern blot hybridization, mixed-challenge infection, and DNA sequence analyses showed that the attenuating defects in the mutants were associated with transposon insertions in rfaL (O antigen ligase), dsbA (thiol:disulfide oxidoreductase), and a new gene, puvA (previously unidentified virulence gene A), with no known homologues. The results indicate the ability of STM to identify novel systemic virulence factors in E. coli K1.

Animals↗
PubMed2002

Identification of in vivo essential genes from Pseudomonas aeruginosa by PCR-based signature-tagged mutagenesis.

We adapted PCR-based signature-tagged mutagenesis (STM) to Pseudomonas aeruginosa. A collection of 1056 mutants was screened in a chronic lung infection rat model. Thirteen mutants were confirmed to be attenuated. Analysis revealed that these STM mutants represented transposon insertions into eight genes previously described in databases, three genes encoding proteins sharing identity with hypothetical proteins and two genes that shared no significant identity with sequences in databases. Five strains mutated in genes involved in protein degradation, stress tolerance, cation transport, ABC transporter, and an unknown protein were shown to be highly attenuated when tested individually in the rat chronic lung infection model.

Cloning, Molecular↗
PubMed2006

Application of signature-tagged mutagenesis to the study of virulence of Erwinia amylovora.

To identify genes that contribute to the virulence of Erwinia amylovora in plants, 1892 mutants were created and screened in pools of < or =96 mutants using signature-tagged mutagenesis. Nineteen mutants were not recovered from apple shoots following inoculation, which suggested that the insertions in these mutants affected genes important for bacterial survival in planta. DNA flanking the Tn5 insertions in the 19 mutants was sequenced and analysed by blast. One mutant had a Tn5 insertion in amsE, a gene involved in the biosynthesis of exopolysaccaride (EPS). Fourteen mutants had insertions in loci that were implicated in biosynthesis or transport of particular amino acids or nucleotides, a site-specific recombinase active during cell division and several putative proteins of unknown function; the flanking DNA of the remaining four mutants lacked significant homology with any DNA in the database. When inoculated individually to hosts, 10 of the 19 mutants caused significantly less disease and multiplied less, as compared with the wild-type strain.

Erwinia amylovora↗
PubMed2004

Gene expression signatures in chronic and aggressive periodontitis: a pilot study.

This pilot study examined gene expression signatures in pathological gingival tissues of subjects with chronic or aggressive periodontitis, and explored whether new subclasses of periodontitis can be identified based on gene expression profiles. A total of 14 patients, seven with chronic and seven with aggressive periodontitis, were examined with respect to clinical periodontal status, composition of subgingival bacterial plaque assessed by checkerboard hybridizations, and levels of serum IgG antibodies to periodontal bacteria assayed by checkerboard immunoblotting. In addition, at least two pathological pockets/patient were biopsied, processed for RNA extraction, amplification and labeling, and used to study gene expression using Affymetrix U-133 A arrays. Based on a total of 35 microarrays, no significantly different gene expression profiles appeared to emerge between chronic and aggressive periodontitis. However, a de novo grouping of the 14 subjects into two fairly robust clusters was possible based on similarities in gene expression. These two groups had similar clinical periodontal status and subgingival bacterial profiles, but differed significantly with respect to serum IgG levels against the important periodontal pathogens Porphyromonas gingivalis, Tannerella forsythensis and Campylobacter rectus. These early data point to the usefulness of gene expression profiling techniques in the identification of subclasses of periodontitis with common pathobiology.

Acute Disease↗
PubMed2006

Metastatic potential of melanomas defined by specific gene expression profiles with no BRAF signature.

The molecular biology of metastatic potential in melanoma has been studied many times previously and changes in the expression of many genes have been linked to metastatic behaviour. What is lacking is a systematic characterization of the regulatory relationships between genes whose expression is related to metastatic potential. Such a characterization would produce a molecular taxonomy for melanoma which could feasibly be used to identify epigenetic mechanisms behind changes in metastatic behaviour. To achieve this we carried out three separate DNA microarray analyses on a total of 86 cultures of melanoma. Significantly, multiple testing correction revealed that previous reports describing correlations of gene expression with activating mutations in BRAF or NRAS were incorrect and that no gene expression patterns correlate with the mutation status of these MAPK pathway components. Instead, we identified three different sample cohorts (A, B and C) and found that these cohorts represent melanoma groups of differing metastatic potential. Cohorts A and B were susceptible to transforming growth factor-beta (TGFbeta)-mediated inhibition of proliferation and had low motility. Cohort C was resistant to TGFbeta and demonstrated high motility. Meta-analysis of the data against previous studies linking gene expression and phenotype confirmed that cohorts A and C represent transcription signatures of weakly and strongly metastatic melanomas, respectively. Gene expression co-regulation suggested that signalling via TGFbeta-type and Wnt/beta-catenin pathways underwent considerable change between cohorts. These results suggest a model for the transition from weakly to strongly metastatic melanomas in which TGFbeta-type signalling upregulates genes expressing vasculogenic/extracellular matrix remodelling factors and Wnt signal inhibitors, coinciding with a downregulation of genes downstream of Wnt signalling.

Amino Acid Motifs↗
PubMed2002

Captive dolphins, Tursiops truncatus, develop signature whistles that match acoustic features of human-made model sounds.

This paper presents a cross-sectional study testing whether dolphins that are born in aquarium pools where they hear trainers' whistles develop whistles that are less frequency modulated than those of wild dolphins. Ten pairs of captive and wild dolphins were matched for age and sex. Twenty whistles were sampled from each dolphin. Several traditional acoustic features (total duration, duration minus any silent periods, etc.) were measured for each whistle, in addition to newly defined flatness parameters: total flatness ratio (percentage of whistle scored as unmodulated), and contiguous flatness ratio (duration of longest flat segment divided by total duration). The durations of wild dolphin whistles were found to be significantly longer, and the captive dolphins had whistles that were less frequency modulated and more like the trainers' whistles. Using a standard t-test, the captive dolphin had a significantly higher total flatness ratio in 9/10 matched pairs, and in 8/10 pairs the captive dolphin had significantly higher contiguous flatness ratios. These results suggest that captive-born dolphins can incorporate features of artificial acoustic models made by humans into their signature whistles.

Animal Communication↗
PubMed1993

A quantitative measure of similarity for tursiops truncatus signature whistles.

Bottlenose dolphins (tursiops truncatus) produce individually distinctive narrow-band "signature whistles." These whistles may be differentiated by the structure of their frequency contours. An algorithm is presented for extracting frequency contours from whistles and comparing two such contours. This algorithm performs nonuniform time dilation to align the contours and provides a quantitative distance measure between the contours. Two recognition experiments using the algorithm on three dolphin whistles from each of five individuals classified 15 out of 15 single-loop whistles correctly, and 14 out of 15 central loops for multiple-loop whistles correctly.

Algorithms↗
PubMed2026

Single-nucleus profiling reveals a core disease signature and cell type-specific vulnerabilities in early Rett syndrome.

Rett syndrome (RTT) is an X-linked neurological disorder caused by MECP2 mutations, creating distinct cellular environments in females (mosaic) versus males (nonmosaic). Despite female patients representing most cases, how mosaicism contributes molecularly to RTT pathogenesis, particularly in presymptomatic stages, remains poorly understood. To address this question, we profiled hippocampal transcriptomes of young female and male RTT mice using bulk and single-nucleus RNA sequencing. We identified a core disease signature of consistently dysregulated genes only in MeCP2- cells across RTT models. Moreover, we uncovered non-cell autonomous effects exclusively in female MeCP2+ excitatory neurons, suggesting that these circuits are more vulnerable early in the mosaic RTT environment. The single-nuclei data also revealed an underappreciated MeCP2- interneuron subtype that had the most transcriptional dysregulation in both male and female RTT hippocampi. Together, these data highlight the different effects of MeCP2 loss on excitatory and inhibitory circuits between the mosaic and nonmosaic environments in early RTT pathogenesis.

Rett Syndrome↗
PubMed2002

A stem cell molecular signature.

Mechanisms regulating self-renewal and cell fate decisions in mammalian stem cells are poorly understood. We determined global gene expression profiles for mouse and human hematopoietic stem cells and other stages of the hematopoietic hierarchy. Murine and human hematopoietic stem cells share a number of expressed gene products, which define key conserved regulatory pathways in this developmental system. Moreover, in the mouse, a portion of the genetic program of hematopoietic stem cells is shared with embryonic and neural stem cells. This overlapping set of gene products represents a molecular signature of stem cells.

Adult↗
PubMed2005

Titan's magnetic field signature during the first Cassini encounter.

The magnetic field signature obtained by Cassini during its first close encounter with Titan on 26 October 2004 is presented and explained in terms of an advanced model. Titan was inside the saturnian magnetosphere. A magnetic field minimum before closest approach marked Cassini's entry into the magnetic ionopause layer. Cassini then left the northern and entered the southern magnetic tail lobe. The magnetic field before and after the encounter was approximately constant for approximately 20 Titan radii, but the field orientation changed exactly at the location of Titan's orbit. No evidence of an internal magnetic field at Titan was detected.

Atmosphere↗