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PubMedDate not supplied

Second metatarsophalangeal joint arthrography: a cadaveric correlation study.

Arthrography of the second metatarsophalangeal joint is an important diagnostic tool to evaluate the integrity of the plantar plate and to aid in the decision process for surgical intervention. A variety of filling patterns have been identified with lesser metatarsophalangeal joint arthrography and their significance with soft-tissue pathology remains to be completely understood. The purpose of this cadaveric study was to evaluate dye patterns in a series of arthrograms of the second metatarsophalangeal joint and to correlate them with identifiable anatomic lesions or structural variants. Thirty-nine cadaveric specimens (including 28 matched pairs) underwent second metatarsophalangeal joint arthrography with a colored radiopaque dye. Arthrographic findings were observed and recorded. Specimens exhibiting dye extravasation outside of the capsular constraints of the joint were dissected to discover any soft-tissue abnormalities. Twenty-one percent of specimens exhibited abnormal extravasation of dye outside of the joint capsule. A plantar plate tear was identified in 2 of these specimens. Filling of the first intermetatarsophalangeal bursa occurred in 6 specimens. However, because this finding was identified in 2 matched pairs, an anatomic variance is suggested rather than a pathologic entity. This cadaveric study shows that anatomic variances exist concerning the second metatarsophalangeal capsule and that arthrography should be correlated with the clinical scenario.

Aged↗
PubMed1991

[Results of transabdominal placental biopsy in the 2nd and 3d trimester].

From August 1988 to October 1990, 115 transabdominal placental biopsies were performed in the second (68%) and third trimenon (32%). The main indication (80%) was the detection of pathological ultrasonographic findings (foetal malformation, growth retardation, oligohydramnios and polyhydramnios). The success rate of chorionic villus sampling (89%) was independent of the localisation of the placenta. A definite cytogenetic result was found in 83% of patients. By combination of placental biopsy and amniocentesis (n = 77) karyotyping was successful in 97% of pregnancies. Chromosomal abnormalities were observed in 15 (13%) cases (7 autosomal and 2 gonosomal aneuploidies, 1 unbalanced translocation, 1 autosomal deletion, 4 structural variants). The outcome of the pregnancies was substantially influenced by the indication for the procedure and by the cytogenetic result. Foetal and peri-/neonatal losses were found in 53% (3% spontaneous abortions) of patients with sonographic abnormalities (n = 92) and in 9% (abortion rate 4%) of pregnancies with regular findings (n = 23). The pregnancy loss rates were 37.7% and 5.9%, respectively. The results confirm the clinical significance of placental biopsy in the management of pregnancies with pathological ultrasonographic findings.

Chorionic Villi↗
PubMed1999

Cognitive dedifferentiation in eidetics and synaesthesia: hunting for the ghost once more.

Both synaesthesia and eidetics have a common characteristic of cognitive dedifferentiation. Synaesthesia (e.g. colour-hearing) entails the dedifferentiation of the sensory modalities, while eidetic imagery entails the dedifferentiation of imagery and perception. One can profitably gain by investigating both within the same study. Moreover, some of the same issues have arisen in these, hitherto, separate research literatures. This behoves a common framework for analysis and investigation. We applied a technique previously used for identifying child eidetikers, for screening the adult population, looking at both phenomena in the same sample. After screening, we selected a total of twenty-nine individuals for controlled testing of both phenomena and their variants (structural eidetic imagery, typographic eidetic imagery, colour-hearing synaesthesia, colour-mood synaesthesia). Our participants also completed a number of questionnaires of relevance (absorption, dissociation, and hallucination). We found that the personality trait of absorption underlies the commonality of experience tapped by both typographic and structural eidetic imagery. Furthermore, the latter phenomena were found to have a common pseudohallucinatory experiential base. For subjects scoring relatively high on the absorption scale, there is a negative correlation between structural eidetic imagery and colour-mood synaesthetic differentiation, replicating to a degree results reported earlier.

Adult↗
PubMed1979

Structure of the antithrombin-binding site in heparin.

Heparin preparations from pig intestinal mucosa and from bovine lung were separated by chromatography on antithrombin-Sepharose into a high-affinity fraction (with high anticoagulant activity) and a low-affinity fraction (with low anticoagulant). Antithrombin-binding heparin fragments (12-16 monosaccharide units) were prepared, either by digesting a high-affinity heparin-antithrombin complex with bacterial heparinase or by partial deaminative cleavage of the unfractionated polysaccharide with nitrous acid followed by affinity chromatography on immobilized antithrombin. Compositional analysis based on separation and identification of deamination products reduced with sodium boro[3H]hydride showed that nonsulfated L-iduronic acid occurred in larger amounts in high-affinity heparin than in low-affinity heparin; furthermore, this component was concentrated in the antithrombin-binding regions of the high-affinity heparin molecules, amounting to approximately one residue per binding site. It is suggested that nonsulfated L-iduronic acid is essential for the anticoagulant activity of heparin. The location of the non-sulfated uronic acid in the antithrombin-binding site was determined by periodate oxidation of antithrombin-binding fragments containing a terminal 2,5-anhydro-D-[1-3H]mannitol unit. Tentative structures for antithrombin-binding sequences in heparin are proposed, including some structural variants believed to be compatible with, but not required for, activity.

Animals↗
PubMed1983

Human hypoxanthine (guanine) phosphoribosyltransferase: an amino acid substitution in a mutant form of the enzyme isolated from a patient with gout.

We have investigated the molecular basis for a deficiency of the enzyme hypoxanthine (guanine) phosphoribosyltransferase (HPRT; IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) in a patient with a severe form of gout. We reported in previous studies the isolation of a unique structural variant of HPRT from this patient's erythrocytes and cultured lymphoblasts. This enzyme variant, which is called HPRTLondon, is characterized by a decreased concentration of HPRT protein in erythrocytes and lymphoblasts, a normal Vmax, a 5-fold increased Km for hypoxanthine, a normal isoelectric point, and an apparently smaller subunit molecular weight. Comparative peptide mapping experiments revealed a single abnormal tryptic peptide in HPRTLondon. Edman degradation of the aberrant peptide from HPRTLondon identified a serine-to-leucine amino acid substitution at position 109. This substitution can be explained by a single nucleotide change in the codon for serine-109 (UCA leads to UUA). Thus a mutation at the HPRT locus has now been defined at the molecular level.

Amino Acid Sequence↗
PubMed1993

Cloning, chromosomal localization, and functional expression of the alpha 1 subunit of the L-type voltage-dependent calcium channel from normal human heart.

A unique structural variant of the cardiac L-type voltage-dependent calcium channel alpha 1 subunit cDNA was isolated from libraries derived from normal human heart mRNA. The deduced amino acid sequence shows significant homology to other calcium channel alpha 1 subunits. However, differences from the rabbit heart alpha 1 include a shortened N-terminus, a unique C-terminal insertion, and both forms of an alternatively spliced motif IV S3 region. The shortened N-terminus provides optimal access to consensus sequences thought to facilitate translation. Northern blot analysis revealed a single hybridizing mRNA species of 9.4 kb. The gene for the human heart alpha 1 subunit was localized specifically to the distal region of chromosome 12p13. The cloned alpha 1 subunit was expressed in Xenopus oocytes and single-channel analyses revealed native-like pharmacology and channel properties.

Amino Acid Sequence↗
PubMed1995

Biosynthetic processing of neu differentiation factor. Glycosylation trafficking, and regulated cleavage from the cell surface.

new differentiation factor (NDF), also known as heregulin, is structurally related to the epidermal growth factor family of growth factors; it stimulates tyrosine phosphorylation of the neu/HER-2 oncogene and causes differentiation of certain human breast cancer cell lines. Alternative splicing of a single gene gives rise to multiple isoforms of NDF/heregulin, as well as the neuronal homologues, designated ARIA (acetylcholine receptor inducing activity) and GGF (glial growth factor); at least 15 structural variants are known. All but two of the NDF/heregulin cDNAs are predicted to encode transmembrane, glycosylated precursors of soluble NDF. In this report we characterized the biosynthetic processing of different NDF isoforms in stably transfected Chinese hamster ovary cells expressing individual NDF isoforms, and in the native cell line Rat 1-EJ, which expresses at least six different NDF isoforms. We found that the precursors for NDF undergo typical glycosylation and trafficking. A portion of the molecules are proteolytically cleaved intracellularly leading to the constitutive secretion of soluble, mature NDF into the culture media. However, a significant portion of the newly synthesized NDF precursor molecules escape intracellular cleavage and are transported to the cell surface of both transfected and native cells, where they reside as full-length, transmembrane proteins. Finally we show that these full-length, transmembrane NDF molecules can undergo phorbol ester regulated cleavage from the membrane, releasing the soluble growth factor into the medium.

Amino Acid Sequence↗
PubMed2000

Requirements for the dGTP-dependent repeat addition processivity of recombinant Tetrahymena telomerase.

Telomerase is a reverse transcriptase responsible for adding simple sequence repeats to chromosome 3'-ends. The template for telomeric repeat synthesis is carried within the RNA component of the telomerase ribonucleoprotein complex. Telomerases can copy their internal templates with repeat addition processivity, reusing the same template multiple times in the extension of a single primer. For some telomerases, optimal repeat addition processivity requires high micromolar dGTP concentrations, a much higher dGTP concentration than required for processive nucleotide addition within a repeat. We have investigated the requirements for dGTP-dependent repeat addition processivity using recombinant Tetrahymena telomerase. By altering the template sequence, we show that repeat addition processivity retains the same dGTP-dependence even if dGTP is not the first nucleotide incorporated in the second repeat. Furthermore, no dNTP other than dGTP can stimulate repeat addition processivity, even if it is the first nucleotide incorporated in the second repeat. Using structural variants of dGTP, we demonstrate that the stimulation of repeat addition processivity is specific for dGTP base and sugar constituents but requires only a single phosphate group. However, all nucleotides that stimulate repeat addition processivity also inhibit or compete with dGTP incorporation into product DNA. By assaying telomerase complexes reconstituted with a variety of altered templates, we find that repeat addition processivity has an unanticipated template or product sequence specificity. Finally, we show that a novel, nascent product DNA binding site establishes dGTP-dependent repeat addition processivity.

Animals↗
PubMed2000

Role of accessory factors and steroid receptor coactivator 1 in the regulation of phosphoenolpyruvate carboxykinase gene transcription by glucocorticoids.

In the liver, glucocorticoids induce a 10-15-fold increase in the rate of transcription of the phosphoenolpyruvate carboxykinase (PEPCK) gene, which encodes a key gluconeogenic enzyme. This induction requires a multicomponent glucocorticoid response unit (GRU) comprised of four glucocorticoid accessory factor (AF) elements and two glucocorticoid receptor binding sites. We show that the AFs that bind the gAF1, gAF2, and gAF3 elements (hepatocyte nuclear factor [HNF]4/chicken ovalbumin upstream promoter transcription factor 1 and HNF3beta) all interact with steroid receptor coactivator 1 (SRC1). This suggests that the AFs function in part by recruiting coactivators to the GRU. The binding of a GAL4-SRC1 chimeric protein completely restores the glucocorticoid induction that is lost when any one of these elements is replaced with a GAL4 binding site. Thus, when SRC1 is recruited directly to gAF1, gAF2, or gAF3, the requirement for the corresponding AF is bypassed. Surprisingly, glucocorticoid receptor is still required when SRC1 is recruited directly to the GAL4 site, suggesting a role for the receptor in activating SRC1 in the context of the GRU. Structural variants of GAL4-SRC1 were used to identify requirements for the basic-helix-loop-helix and histone acetyltransferase domains of SRC1, and these are specific to the region of the promoter to which the coactivator is recruited.

Base Sequence↗
PubMed2001

The unique proline of the Prochlorothrix hollandica plastocyanin hydrophobic patch impairs electron transfer to photosystem I.

A number of surface residues of plastocyanin from Prochlorothrix hollandica have been modified by site-directed mutagenesis. Changes have been made in amino acids located in the amino-terminal hydrophobic patch of the copper protein, which presents a variant structure as compared with other plastocyanins. The single mutants Y12G, Y12F, Y12W, P14L, and double mutant Y12G/P14L have been produced. Their reactivity toward photosystem I has been analyzed by laser flash absorption spectroscopy. Plots of the observed rate constant with all mutants versus plastocyanin concentration show a saturation profile similar to that with wild-type plastocyanin, thus suggesting the formation of a plastocyanin-photosystem I transient complex. The mutations do not induce relevant changes in the equilibrium constant for complex formation but induce significant variations in the electron transfer rate constant, mainly with the two mutants at proline 14. Additionally, molecular dynamics calculations indicate that mutations at position 14 yield small changes in the geometry of the copper center. The comparative kinetic analysis of the reactivity of plastocyanin mutants toward photosystem I from different organisms (plants and cyanobacteria) reveals that reversion of the unique proline of Prochlorothrix plastocyanin to the conserved leucine of all other plastocyanins at this position enhances the reactivity of the Prochlorothrix protein.

Bacterial Proteins↗
PubMed1997

Differential regulation and function of CD73, a glycosyl-phosphatidylinositol-linked 70-kD adhesion molecule, on lymphocytes and endothelial cells.

CD73, otherwise known as ecto-5'-nucleotidase, is a glycosyl-phosphatidylinositol-linked 70-kD molecule expressed on different cell types, including vascular endothelial cells (EC) and certain subtypes of lymphocytes. There is strong evidence for lymphocyte CD73 having a role in several immunological phenomena such as lymphocyte activation, proliferation, and adhesion to endothelium, but the physiological role of CD73 in other cell types is less clear. To compare the biological characteristics of CD73 in different cell types, we have studied the structure, function, and surface modulation of CD73 on lymphocytes and EC. CD73 molecules on lymphocytes are shed from the cell surface as a consequence of triggering with an anti-CD73 mAb, mimicking ligand binding. In contrast, triggering of endothelial CD73 does not have any effect on its expression. Lymphocyte CD73 is susceptible to phosphatidylinositol phospholipase, whereas only a small portion of CD73 on EC could be removed by this enzyme. Furthermore, CD73 on EC was unable to deliver a tyrosine phosphorylation inducing signal upon mAb triggering, whereas triggering of lymphocyte CD73 can induce tyrosine phosphorylation. Despite the functional differences, CD73 molecules on lymphocytes and EC were practically identical structurally, when studied at the protein, mRNA, and cDNA level. Thus, CD73 is an interesting example of a molecule which lacks structural variants but yet has a wide diversity of biological functions. We suggest that the ligand-induced shedding of lymphocyte CD73 represents an important and novel means of controlling lymphocyte-EC interactions.

5'-Nucleotidase↗
PubMed1974

Mitochondrial DNA replication in sea urchin oocytes.

Mitochondrial DNA (mtDNA) replicative intermediates from Strongylocentrotus purpuratus oocytes were isolated by ethidium bromide-CsCl density gradient centrifugation and examined by electron microscopy after formamide spreading. In some experiments, the mtDNA was radioactively labeled by exposing isolated oocytes to [(3)H]thymidine. Oocyte mtDNA replication appears to follow the displacement loop model outlined in mouse L cells. There are differences in detail. The frequency of D-loop DNA is much lower in oocytes, suggesting that the relative holding time at the D-loop stage is shorter. Duplex synthesis on the displaced strand occurs early and with multiple initiations. The frequency of totally duplex replicative forms, or Cairns' forms, is the highest reported for mtDNA. The differences may be related to the fact that oocyte mtDNA replication occurs in the absence of cell division and need not be coordinated with a cell cycle. Molecules with expanded D loops banded in the intermediate region between the lower and upper bands in an ethidium bromide-CsCl gradient, supporting the notion that displacement replication proceeds on a closed circular template which is subject to nicking-closing cycles. In mature sea urchin eggs, replicative forms are absent and virtually all the mtDNA is stored as clean circular duplexes. Some novel structural variants of superhelical circular DNA (molecules with denaturation loops and double branch-migrated replicative forms) are reported.

Animals↗
PubMed1996

Partial signaling by CD8+ T cells in response to antagonist ligands.

Structural variants of an agonist peptide-major histocompatibility complex (MHC) molecule ligand can show partial agonist and/or antagonist properties. A number of such altered ligands appear to act as pure antagonists. They lack any detectable ability to induce T cell effector function and have been described as unable to induce calcium transients and turnover of inositol phosphates. This has been interpreted as an inability of these ligands to initiate any T cell receptor (TCR)-dependent signal transduction, with their antagonist properties ascribed to competition with offered agonist for TCR occupancy. Yet antagonists for mature CD8+ T cells can induce positive selection of thymocytes, implying active induction of T cell differentiation events, and partial agonists or agonist/antagonist combinations elicit a distinctive pattern of early TCR-associated tyrosine phosphorylation events in CD4+ T cells. We have therefore directly examined proximal TCR signaling in a CD8+ T cell line in response to various related ligands. TCR engagement with natural peptide-MHC class I agonist resulted in the same pattern of early TCR-associated tyrosine phosphorylation events as seen with CD4+ cells, including accumulation of both the p21 and p23 forms of phosphorylated zeta, phosphorylation of CD3 epsilon, and association of phosphorylated ZAP-70 with the TCR. Two antagonists that lacked the ability to induce any detectable CTL effector response (cytolysis, esterase release, gamma interferon secretion, interleukin-2 receptor alpha upregulation) were nevertheless found to also induce TCR-dependent phosphorylation events. In these cases, there was preferential accumulation of the p21 form of phospho-zeta without net phosphorylation of CD3 epsilon, as well as the association of nonphosphorylated ZAP-70 kinase with the receptor. These data show that variant ligands induce similar TCR-dependent phosphorylation events in CD8+ T cells as first observed in CD4+ cells. More importantly, they demonstrate that some putatively pure antagonists are actually a subset of partial agonists able to induce intracellular biochemical changes through the TCR. This delivery of a partial signal by antagonists raises the possibility that antagonism in some cases may result from active interference with stimulation of effector activity by agonist in mature T cells, while the same variant signal could selectively trigger intracellular events that allow positive without negative selection in thymocytes.

Amino Acid Sequence↗
PubMed2003

Normally functioning murF is essential for the optimal expression of methicillin resistance in Staphylococcus aureus.

A carboxy-terminal fragment of murF was used to construct and insert a suicide plasmid into the chromosomal copy of the gene in the highly and homogeneously methicillin-resistant Staphylococcus aureus (MRSA) strain COL by Campbell type integration. The plasmid insertion generated a mutant in which the MIC value for oxacillin was reduced from 400 microg/ml of the parental strain to 0.75 microg/ml in 90% of the cells of the mutant cultures that were heterogeneous: they contained subpopulations of bacteria with a frequency of 10(-3) that were capable of expressing resistance at nearly the parental level. The impact of the murF mutation on antibiotic resistance was selective for beta-lactam antibiotics: there was no change in the susceptibility of the mutant to D-cycloserine, fosfomycin, beta-D-chloro-alanine, moenomycin, bacitracin, or vancomycin. Analysis of the mutant peptidoglycan showed decrease in the percentage of oligomeric components in rough proportion to the accumulation of several abnormal muropeptide components, which were identified as structural variants of the disaccharide tripeptide monomer. An abnormal cell wall precursor identified as UDP MurNac tripeptide was also detected in the cytoplasmic pool of the mutant strain. A normal proportion of oligomers and a greatly reduced representation of the disaccharide tripeptide were demonstrated in the cell wall of the murF mutant's subpopulation that has retained the parental level of resistance. Northern analysis demonstrated a drastic reduction in the transcription rate of mecA in mutant F9 whereas mecA transcription increased in the subpopulation of bacteria that retained high-level resistance.

Amino Acid Sequence↗
PubMed2025

Generating multiple alignments on a pangenomic scale.

MOTIVATION: Since novel long read sequencing technologies allow for de novo assembly of many individuals of a species, high-quality assemblies are becoming widely available. For example, the recently published draft human pangenome reference was based on assemblies composed of contigs. There is an urgent need for a software-tool that is able to generate a multiple alignment of genomes of the same species because current multiple sequence alignment programs cannot deal with such a volume of data. RESULTS: We show that the combination of a well-known anchor-based method with the technique of prefix-free parsing yields an approach that is able to generate multiple alignments on a pangenomic scale, provided that large-scale structural variants are rare. Furthermore, experiments with real world data show that our software tool PANgenomic Anchor-based Multiple Alignment significantly outperforms current state-of-the art programs. AVAILABILITY AND IMPLEMENTATION: Source code is available at: https://gitlab.com/qwerzuiop/panama, archived at swh:1:dir:e90c9f664995acca9063245cabdd97549cf39694.

Software↗
PubMed2025

nf-core/pacvar: a pipeline for analyzing long-read PacBio whole genome and repeat expansion sequencing data.

MOTIVATION: Pacific Biosciences (PacBio) single-molecule, long-read sequencing enables whole genome annotation and the characterization of 20 complex repetitive repeat regions, especially relevant to neurodegenerative diseases, through their PureTarget panel. Long-read whole-genome sequencing (WGS) also allows for the detection of structural variants that would be difficult to detect with traditional short-read sequencing. However, the raw unaligned Binary Alignment Map data need to be processed before analysis. There is a need for an intuitive comprehensive bioinformatic pipeline that can analyze these data. RESULTS: We present nf-core/pacvar, a comprehensive pipeline for analyzing both PacBio single-molecule PureTarget and WGS data that demultiplexes and parallelizes pre-processing, variant calling and repeat characterization. nf-core/pacvar is compatible with little configuration and has few dependencies. This pipeline enables rapid end-to-end, parallel processing of PacBio single-molecule whole genome and targeted repeat expansion sequencing. AVAILABILITY AND IMPLEMENTATION: nf-core/pacvar is available on nf-core website (https://nf-co.re/pacvar/) and on github (https://github.com/nf-core/pacvar) under MIT License (DOI: 10.5281/zenodo.14813048).

Software↗
PubMed2025

SVbyEye: a visual tool to characterize structural variation among whole-genome assemblies.

MOTIVATION: We are now in the era of being able to routinely generate highly contiguous (near telomere-to-telomere) genome assemblies of human and nonhuman species. Complex structural variation and regions of rapid evolutionary turnover are being discovered for the first time. Thus, efficient and informative visualization tools are needed to evaluate and directly observe structural differences between two or more genomes. RESULTS: We developed SVbyEye, an open-source R package to visualize and annotate sequence-to-sequence alignments along with various functionalities to process these alignments. The tool facilitates the characterization of complex structural variants in the context of sequence homology helping resolve the mechanisms underlying their formation. AVAILABILITY AND IMPLEMENTATION: SVbyEye is available on GitHub (https://github.com/daewoooo/SVbyEye) and via Zenodo (https://doi.org/10.5281/zenodo.15303553).

Software↗
PubMed2026

PULPO: pipeline of understanding large-scale patterns of oncogenomic signatures.

SUMMARY: PULPO v1.0 is a novel; fully automated pipeline designed for the preprocess and extraction of mutational signatures from raw Optical Genome Mapping (OGM) data. Built using Snakemake and executed within an isolated, Conda-managed environment, PULPO transforms complex cytogenetic alterations, captured at ultra-high resolution, into Catalogue of somatic mutations in cancer mutational signatures (COSMIC). This innovative approach not only enables researchers to work directly from raw OGM inputs but also streamlines the traditionally complex process of signature extraction, making advanced oncogenomic analyses accessible to users with varying levels of bioinformatics expertise. By facilitating the integration of comprehensive structural variants (SVs) and copy number variants (CNVs) data with established signature catalogues, PULPO paves the way for improved diagnostic accuracy and personalized therapeutic strategies. AVAILABILITY AND IMPLEMENTATION: The pipeline is open source and freely available under the MIT License at https://github.com/OncologyHNJ/PULPO-v.1.0 and DOI in Zenodo: https://zenodo.org/records/17749097.

Software↗