Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Structure variation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,477 records · Page 82Linked to original sources
PubMed1979

Structural polymorphism of human DR antigens.

DR ANTIGENS are polymorphic cell surface molecules whose expression is controlled by a locus closely linked or identical to the D locus of the major histocompatibility complex (MHC) of man (for reviews see refs 1, 2). They are functionally and structurally homologous to the murine la antigens determined by the I-E subregion of the MHC, a region which has been implicated in the genetic control of immune responses(3,4). Both sets of antigens are mainly expressed on cells associated with immune function (for reviews see refs 1, 2, 5), and are involved in mediating T-cell, B-cell and macrophage interactions required for the generation of immune responses(6-9). In addition, both consist of two non-covalently associated polypeptides, designated alpha and beta, with molecular weights of 34,000 and 28,000, respectively(10). The association of some DR antigens with increased susceptibility to certain diseases (for review see ref. 1) and the genetic restrictions imposed on cellular interactions by the HLA-D region(9,11) may represent the effects of structural variability among DR antigens. The aim of the studies reported here was to examine the nature and degree of structural variation among DR antigens isolated from cultured lymphoid B cells with different DR phenotypes. Such information may provide an understanding of the molecular mechanisms by which DR antigens mediate their function.

Journal Article↗
PubMed1978

The structure of tumours derived from mouse submandibular gland epithelium transformed in vitro.

The morphology and ultrastructure of 48 primary tumours established from 5 cell lines of adult mouse salivary gland epithelial cells transformed in vitro are described. Tumours from 4 of the cells lines were adenocarcinomas with a wide range of structural variation, and resembled human salivary gland carcinomas. The fifth cell line produced tumours with carcinomatous and sarcomatous elements.

Animals↗
PubMed2001

Cleavage of purified neuronal clathrin assembly protein (CALM) by caspase 3 and calpain.

The most efficient means of protein internalization from the membrane are through clathrin-coated pits, which concentrate protein interactions with the clathrin-associated assembly protein complex AP-2 and internalization signals in the cytoplasmic domain of transmembrane proteins. Binding of clathrin assembly protein to clathrin triskelia induces their assembly into clathrin-coated vesicles (CCVs). Due to a difficulty of isolating clathrin molecules from their complex or assembly state in the cells, most of the studies were carried out with recombinant clathrin proteins, which may present different conformation and structural variation. In this study, we have developed an efficient method of isolating the native clathrin assembly protein lymphoid myeloid (CALM) from the bovine brain that is enriched with clathrin and clathrin associated proteins and characterized by their sensitivity to proteases and it's ability to form CCV. The purified CALM has molecular weight of approximately 100,000 dalton on SDS-PAGE, which is consistent with the result of in vitro translation. The purified CALM protein could promote the assembly of clathrin triskelia into clathrin cage, and cleaved CALM proteolysed by caspase 3 and calpain could not promote them. In this respect, our data support a model in which CALM functions like AP180 as a monomeric clathrin assembly protein and might take part in apoptotic process in neuronal cells.

Adaptor Proteins, Vesicular Transport↗
PubMed2004

A 'checkerboard' electronic crystal state in lightly hole-doped Ca2-xNaxCuO2Cl2.

The phase diagram of hole-doped copper oxides shows four different electronic phases existing at zero temperature. Familiar among these are the Mott insulator, high-transition-temperature superconductor and metallic phases. A fourth phase, of unknown identity, occurs at light doping along the zero-temperature bound of the 'pseudogap' regime. This regime is rich in peculiar electronic phenomena, prompting numerous proposals that it contains some form of hidden electronic order. Here we present low-temperature electronic structure imaging studies of a lightly hole-doped copper oxide: Ca2-xNaxCuO2Cl2. Tunnelling spectroscopy (at energies |E| > 100 meV) reveals electron extraction probabilities greatly exceeding those for injection, as anticipated for a doped Mott insulator. However, for |E| < 100 meV, the spectrum exhibits a V-shaped energy gap centred on E = 0. States within this gap undergo intense spatial modulations, with the spatial correlations of a four CuO2-unit-cell square 'checkerboard', independent of energy. Intricate atomic-scale electronic structure variations also exist within the checkerboard. These data are consistent with an unanticipated crystalline electronic state, possibly the hidden electronic order, existing in the zero-temperature pseudogap regime of Ca2-xNaxCuO2Cl2.

Journal Article↗
PubMed2006

Assaying chromosomal inversions by single-molecule haplotyping.

Inversions are an important form of structural variation, but they are difficult to characterize, as their breakpoints often fall within inverted repeats. We have developed a method called 'haplotype fusion' in which an inversion breakpoint is genotyped by performing fusion PCR on single molecules of human genomic DNA. Fusing single-copy sequences bracketing an inversion breakpoint generates orientation-specific PCR products, exemplified by a genotyping assay for the int22 hemophilia A inversion on Xq28. Furthermore, we demonstrated that inversion events with breakpoints embedded within long (>100 kb) inverted repeats can be genotyped by haplotype-fusion PCR followed by bead-based single-molecule haplotyping on repeat-specific markers bracketing the inversion breakpoint. We illustrate this method by genotyping a Yp paracentric inversion sponsored by >300-kb-long inverted repeats. The generality of our methods to survey for, and genotype chromosomal inversions should help our understanding of the contribution of inversions to genomic variation, inherited diseases and cancer.

Chromosome Inversion↗
PubMed2025

Molecular characterization of JC virus in progressive multifocal leukoencephalopathy cases from India.

Progressive Multifocal Leukoencephalopathy (PML) is a rare, often fatal demyelinating disease of the central nervous system caused by reactivation of the John Cunningham virus (JCV) in immunocompromised individuals. Despite an estimated 2.4 million people living with HIV in India, the reported incidence of PML remains lower than in Western countries, likely due to underdiagnosis, underreporting, and distinct host genetic and viral factors. The rising number of individuals on immunosuppressive therapies, including organ transplant recipients and those with autoimmune disorders, further emphasizes the need to study JC virus diversity in the Indian context. This study aimed to characterize the genetic diversity of JCV in India by sequencing the VP1 and non-coding control region (NCCR) from cerebrospinal fluid (n=30) of confirmed PML cases using Sanger sequencing. VP1 sequencing (n=23) revealed a predominance of genotypes 2 (subtypes 2D, 2A, 2B) and 3A. NCCR analysis (n=17) showed extensive rearrangements relative to the archetype form, with most sequences classified as Type II-R. Structural variations, including deletions, duplications, and insertions were common, particularly in blocks D, C, and F. Transcription factor binding sites (TFBS) were identified for TATA box, Tst-1, SP-1, p53, CEBPB, AP-1, NF-1, EGR-1, GF-1, CRE-TAR and NFkB. Additional TFBS were created due to rearrangements, often spanning two blocks. These findings underscore the genomic diversity of JCV in India and highlight the need for continued molecular surveillance to better understand its implications for high-risk populations.

Leukoencephalopathy, Progressive Multifocal↗
PubMed2000

Hunting for human obesity genes? Look in the adipose tissue!

Over-eating and physical inactivity in combination with genetic factors play the most important roles in the development of over weight in humans. The common genetic components behind excess accumulation of body fat are so far unknown. Studies of candidate genes indicate that most of the genes that associate with obesity control important functions of adipose tissue as well. Furthermore, structural variations in these genes may alter adipose tissue function in a way that promotes obesity. The genes which both are functional in human adipose tissue and associate with obesity are: hormone sensitive lipase, beta2 and beta3-adrenoceptors, tumor necrosis factor alpha, low density lipoprotein receptor, uncoupling protein-1 and peroxisome proliferator activated receptor gamma-2. Other genes are mostly important for obesity among women (for example beta2 -and beta3-adrenoceptors, low density lipoprotein receptor and tumor necrosis factor alpha). Some of these genes may promote obesity by gene-gene interactions (for example beta3-adrenoceptors and uncoupling protein-1) or gene-environmental interactions (for example beta2-adrenoceptors and physical activity). Few genes with no known function in adipose tissue have shown a firm association with excess body fat. The latter suggests that the important human obesity genes also control adipose tissue function. Therefore it might be of value to focus the further hunt for obesity genes on the fat tissue.

Adipose Tissue↗
PubMed1999

Chemical structure and function of glycosphingolipids of Sphingomonas spp and their distribution among members of the alpha-4 subclass of Proteobacteria.

Sphingomonas spp are phylogenetically placed in the alpha-4 subclass of Proteobacteria. They have glycosphingolipids (GSL) in their membranes instead of lipopolysaccharide (LPS) as in other Gram-negative bacteria. S. paucimobilis, the type species of the genus, has GSL-1, which contains only glucuronic acid (GlcA) as a sugar moiety, and GSL-4A, which contains a tetrasaccharide including GlcA. GSL-1 and GSL-4A form the outer membrane of S. paucimobilis with outer membrane proteins and phospholipids. In the outer membrane, GSLs are assumed to locate and function as does the LPS of other Gram-negative bacteria. Sphingomonas spp closely related to the type species contain both GSL-1 and the oligosaccharide-type GSL such as GSL-4A, but other Sphingomonas spp and other genera in the alpha-4 subclass of Proteobacteria contain only GSL-1. Structural variations of fatty acids and dihydrosphingosines in the GSL-1 are presented.

Journal Article↗
PubMed1998

A variant transcript encoding an isoform of the human protein tyrosine kinase EPHB2 is generated by alternative splicing and alternative use of polyadenylation signals.

We previously isolated and characterized cDNA clones of DRT (EPHB2), encoding a receptor protein-tyrosine kinase of the EPH family. Northern blot analysis showed that EPHB2 transcripts are expressed in three sizes of approximately 4, 5, and 11 kb, suggesting that these transcripts are generated by alternative splicing and/or alternative use of polyadenylation sites. To explore this possibility, we isolated additional EPHB2 cDNA clones, including clone 5K-1, by re-screening the human fetal brain cDNA library. Nucleotide sequence analysis of clone 5K-1 revealed that it represents a variant transcript of EPHB2 (EPHB2v). Relative to the EPHB2 cDNA sequence previously reported, clone 5K-1 has two coding region deletions of 3 and 93 nucleotides. Nucleotide sequence analyses of EPHB2 genomic DNA fragments corresponding to these deletions suggest that the EPHB2v transcript is generated by alternative splicing. The 3' end of clone 5K-1 contains a polyadenosine stretch preceded by a potential polyadenylation signal, which is not used to generate the EPHB2 transcript. Taken together, these data indicate that EPHB2v is generated by both alternative splicing and alternative use of polyadenylation sites. The EPHB2v protein lacks one arginine residue that resides immediately following the EPHB2 transmembrane domain. In contrast, as a result of the frame shift caused by the 93 nucleotide deletion, the C-terminus of the EPHB2v protein is longer by 70 amino acids than that of EPHB2. We also show that the human neuroblastoma cell line SY5Y and NTera-2N neurons express high levels of EPHB2 and lower levels of EPHB2v. These structural variations found between the EPHB2 and EPHB2v proteins may reflect functional heterogeneity of EPHB2.

Alternative Splicing↗
PubMed2004

Tin(IV) halide complexes of AsPh3) The structures of trans-SnCl4(AsPh3)2 and SnBr4(AsPh3).AsPh3.

The structures of two 1 : 2 adducts between tin(IV) halides and AsPh(3) have been determined. SnCl(4)(AsPh(3))(2) adopts a six-coordinate geometry at tin in which the two organoarsine donors are mutually trans. In contrast, SnBr(4)(AsPh(3))(2) is five-coordinate at tin and only one arsine is directly bonded to the metal, in an axial site of the trigonal bipyramid. The second AsPh(3) group has a close contact with the axially bound bromine [As...Br: 3.567(3) angstroms], which is a unique structural variation that depicts an intermediate in a halogen-transfer reaction between Group 14 and Group 15 elements. AACVD using SnCl(4)(AsPh(3))(2) generates a film containing SnO(2) and a second crystalline material which is possibly SnCl(2), but which contains no arsenic.

Journal Article↗
PubMed2006

Pyrazolyl-functionalized 2-methylimidazolium-based ionic liquids and their palladium(II) complexes as recyclable catalysts.

A series of pyrazolyl- and 3,5-dimethylpyrazolyl-functionalized 2-methylimidazolium-based salts have been prepared through neat reactions of 1-pyrazolylmethylene-2-methylimidazole and 1-(3,5-dimethylpyrazolylmethylene)-2-methylimidazole with alkyl or polyfluoroalkyl iodides or 1-bromohexane, followed by anion exchange with LiN(SO2CF3)2 or KPF6. Their thermal properties were determined by DSC and TGA. Most of the bis(trifluoromethanesulfonyl)amide salts are room temperature ionic liquids. The influence of anions and of the structural variation in the 2-methylimidazolium-based cations on the physicochemical properties is discussed. These salts reacted easily with palladium(II) chloride to generate mononuclear palladium ionic liquid complexes. The catalytic activity and recyclability of the palladium complexes in the corresponding ionic liquids were preliminarily examined using Heck, Suzuki and Sonogashira cross-coupling reactions in the absence of phosphine ligands.

Journal Article↗
PubMed2006

Effect of Sr content on the crystal structure and electrical properties of the system La2-xSrxNiO4+delta (0 <or=x<or= 1).

Materials formulated as La(2-x)Sr(x)NiO(4+delta) (0 <or=x<or= 1) have been prepared and investigated by high-resolution neutron powder diffraction in order to correlate the structural variation induced by the incorporation of Sr into the crystal lattice with the electronic and thermal properties of each material. The evolution of the electrical conductivity and thermal expansion coefficients with temperature have been determined in order to study the potential use of these compounds as cathodes for intermediate-temperature solid oxide fuel cells (IT-SOFC). These oxides show a good thermal expansion coefficient (TEC = 11-13 x 10(-6) K(-1)), and high electronic conductivity up to 273 S cm(-1). It is noticeable that a great enhancement of the electrical conductivity with the Sr content is concomitant with the shortening of the Ni-O1 bond length.

Journal Article↗
PubMed1977

The degradation of cartilage proteoglycans by tissue proteinases. Proteoglycan heterogeneity and the pathway of proteolytic degradation.

1. CaCl2-extracted proteoglycan from bovine nasal cartilage was degraded by four tissue proteinases till no further decrease in hydroynamic size was obtained. The proteoglycan and its final degradation products were then fractionated by Sepharose 2B chromatography. 2. The average size of the degradation products was least for cathepsin B and lysosomal elastase, and greatest for cathepsin D and cathepsin G. The latter two proteinases also produced degradation products that showed the widest range of sizes. 3. The structure of the degradation products ranged from peptides containing a single glycosaminoglycan chain to those containing twelve or more chains. Of the four proteinases, only cathepsin B produced peptides that contained a single chondroitin sulphate chain. 4. The proteoglycan was very heterogeneous with respect to size and chemical composition. Its behaviour on electrophoresis suggested that at least two genetically distinct core proteins might exist. 5. Irrespective of their structural variations, all proteoglycan molecules were able to interact with hyaluronic acid. In contrast, none of the degradation products were capable of this type of interaction. 6. A pathway for the proteolytic degradation of proteoglycans is postulated in which the sites of initial cleavage may be common to the majority of proteinases, whereas the production of the final clusters is dependent on the specificity of the proteinase. Only those proteinases of broadest specificity can produce single-chain chondroitin sulphate-peptides.

Animals↗
PubMed2004

Truncated variants of hyaluronan-binding protein 1 bind hyaluronan and induce identical morphological aberrations in COS-1 cells.

Hyaluronan (HA)-binding protein 1 (HABP1) is multifunctional in nature and exists as a trimer through coiled-coil interaction between alpha-helices at its N- and C-termini. To investigate the importance of trimeric assemblage and HA-binding ability of HABP1, we generated and overexpressed variants of HABP1 by truncating the alpha-helices at its termini. Subsequently, these variants were transiently expressed in COS-1 cells to examine the influence of these structural variations on normal cell morphology, as compared with those imparted by HABP1. Substantiating the centrality of coiled-coil interaction for maintaining the trimeric assembly of HABP1, we demonstrate that disruption of trimerization does not alter the affinity of variants towards its ligand HA. Transient expression of HABP1 altered the morphology of COS-1 cells by generating numerous cytoplasmic vacuoles along with disruption of the f-actin network. Interestingly, the truncated variants also imparted identical morphological changes. Characterization of the cytoplasmic vacuoles revealed that most of these vacuoles were autophagic in nature, resembling those generated under stress conditions. The identical morphological changes manifested in COS-1 cells on transient expression of HABP1 or its variants is attributed to their comparable HA-binding ability, which in concert with endogenous HABP1, may deplete the cellular HA pool. Such quenching of HA below a threshold level in the cellular milieu could generate a stress condition, manifested through cytoplasmic vacuoles and a disassembly of the f-actin network.

Alternative Splicing↗
PubMed1989

Human serum amyloid A protein. Behaviour in aqueous and urea-containing solutions and antibody production.

Human serum amyloid A protein (apo-SAA) can be prepared by gel filtration of delipidated acute-phase high-density lipoprotein in the presence of urea. The resultant apo-SAA is soluble (greater than 90% solubility) in a wide range of buffer solutions, with all of the six major isoforms of apo-SAA being equally soluble. In urea-containing solutions the isoforms behave qualitatively differently in various urea concentrations, probably reflecting subtle primary-structure variations. The higher-pI isoforms are only completely unfolded at greater than 7 M-urea. By immunizing with apo-SAA adsorbed to acid-treated bacteria (Salmonella minnesota R595), high-titre antibodies can easily be elicited in rabbits.

Adsorption↗
PubMed1993

Non-proteoglycan forms of biglycan increase with age in human articular cartilage.

Polyclonal anti-peptide antibodies were raised to the C-terminal regions of human biglycan and decorin. These antibodies were used in immunoblotting to study structural variations with age in the proteoglycan core proteins present in extracts of human articular cartilage and intervertebral disc. Three forms of the biglycan core protein were identified. The largest form was detected only after chondroitinase treatment and represents the proteoglycan form of the molecule from which the glycosaminoglycan chains have been removed. However, chondroitinase treatment did not alter the electrophoretic mobility of the two smaller proteins, which appear to represent non-proteoglycan forms of the molecule, resulting either from a failure to substitute the intact proteoglycan core protein with glycosaminoglycan chains during its synthesis or from proteolytic processing of the intact proteoglycan causing removal of the N-terminal region bearing the glycosaminoglycan chains. The non-proteoglycan forms constituted a minor proportion of biglycan in the newborn, but were the major components in the adult. A similar trend was seen in both articular cartilage and intervertebral disc. In comparison, decorin appears to exist predominantly as a proteoglycan at all ages, with two core protein sizes being present after chondroitinase treatment. Non-proteoglycan forms were detected in the adult, but they were always a minor constituent.

Adolescent↗
PubMed1994

Topoisomerase I action on the heterochromatic DNA from the brine shrimp Artemia franciscana: studies in vivo and in vitro.

The genomes of higher eukaryotes contain various amounts of tandem repeated DNA sequences (satellite DNA) typically located in the constitutive heterochromatin, the most highly condensed region of interphase chromosomes. We have previously demonstrated that an AluI DNA family of repeats is the major component of constitutive heterochromatin in the brine shrimp Artemia franciscana. The analysis of cloned heterochromatic fragments revealed that this repetitive DNA shows a stable curvature conferring a solenoidal geometry to the double helix. In this paper we provide evidence, using the antitumour drug camptothecin, that, in vivo, topoisomerase I cleaves heterochromatin with a frequency comparable with that observed in the whole genome. The analysis of the break sites shows that the enzyme cleaves heterochromatic DNA at specific sites characterized by a degenerate consensus sequence. Moreover the enzyme-mediated breaks have, in vitro, a degenerate consensus sequence similar to, but not identical with, the in vivo one. Some of these sites are influenced by the DNA flanking the heterochromatic insert, suggesting that structural variations could modify the enzyme specificity.

Animals↗
PubMed2004

Permeability studies of alkylamides and caffeic acid conjugates from echinacea using a Caco-2 cell monolayer model.

BACKGROUND: Echinacea is composed of three major groups of compounds that are thought to be responsible for stimulation of the immune system--the caffeic acid conjugates, alkylamides and polysaccharides. This study has focussed on the former two classes, as these are the constituents found in ethanolic liquid extracts. OBJECTIVE: To investigate the absorption of these two groups of compounds using Caco-2 monolayers, which are a model of the intestinal epithelial barrier. RESULTS: The caffeic acid conjugates (caftaric acid, echinacoside and cichoric acid) permeated poorly through the Caco-2 monolayers although one potential metabolite, cinnamic acid, diffused readily with an apparent permeability (Papp) of 1 x 10(-4) cm/s. Alkylamides were found to diffuse through Caco-2 monolayers with Papp ranging from 3 x 10(-6) to 3 x 10(-4) cm/s. This diversity in Papp for the different alkylamides correlates to structural variations, with saturation and N-terminal methylation contributing to decreases in Papp. The transport of the alkylamides is not affected by the presence of other constituents and the results for synthetic alkylamides were in line with those for the alkylamides in the echinacea preparation. CONCLUSION: Alkylamides but not caffeic acid conjugates are likely to cross the intestinal barrier.

Amides↗