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At least 721 records · Page 40Linked to original sources
PubMed1980

Differences among subfractions of H1 histone in retention of linear and superhelical DNA on filters.

Four kinds of rabbit thymus H1 histone differ among themselves in their ability to retain DNA on nitrocellulose filters. This is true for linear, or superhelical DNA, but the order of effectiveness of the different H1 histones depends on the physical conformation of the DNA. For linear DNA the binding efficiencies of the H1 histones are: RTL2 = RTL3 greater than RTL4 greater than RTL1. This order of effectiveness parallels the effectiveness of the H1 histones previously found for the condensation of linear DNA as observed by circular dichroism and viscosity. The binding efficiencies of the various histones toward superhelical DNA were: RTL4 greater than RTL3 greater than RTL1 greater than RTL2. The variation in amino acid sequence between different rabbit thymus H1 histones might thus introduce structural variations in nucleohistone fibers and perhaps in chromatin.

Animals↗
PubMed1986

Quantitative variations of the C3b/C4b receptor (CR1) in human erythrocytes are controlled by genes within the regulator of complement activation (RCA) gene cluster.

The genetic relationships of quantitative and structural variations of the C3b/C4b receptor (CR1) in human erythrocytes have been analyzed in informative families. Our results demonstrate the existence of multiple discrete quantitative variations of CR1 controlled by a locus, C3bRQ, closely linked to the CR1 structural locus, C3bR. Since the amounts of CR1 produced by each C3bR allele are shown to be independently regulated, we propose that a cis-acting genetic mechanism controls the level of expression of the C3bR alleles, and that this quantitative control plays a major, if not the sole, role in determining the total amounts of CR1 on normal human erythrocytes.

Alleles↗
PubMed1988

Morphometric analysis of the human corpus callosum and anterior commissure.

The cross-sectional areas of the corpus callosum (CC) and anterior commissure (AC) were determined by computer-assisted morphometry in normal human brains obtained at autopsy. In addition, the shape of each CC was examined qualitatively by three "blind" observers. A two-fold variation was observed in the cross-sectional area of the CC. Surprisingly, callosal cross-sectional area was not significantly related to brain weight. Moreover, contrary to recent reports, neither simple inspection nor morphometry revealed structural variation related to sex. A striking, seven-fold, variation was observed in the cross-sectional area of the AC. However, AC cross-sectional area was not related either to brain weight or CC cross-sectional area. A trend toward sexual dimorphism in AC cross-sectional area was observed, with males having the larger AC's. Since the interhemispheric commissures are composed, to a large extent, of fibers that link the various cortical areas of the two hemispheres, these observations suggest that variation in the cross-sectional area of the interhemispheric commissures is not simply related to brain weight or sex but, rather, reflects a similar degree of variation in some aspect of cortical structure.

Brain↗
PubMed1987

Structural abnormalities of the hair shaft.

Abnormalities of the hair shaft are varied and often confusing. They do require accurate recognition, which can be helpful in the diagnosis and management of a hair disorder, or in the detection of underlying disease. A reliable evaluation of hair shaft abnormality is dependent on familiarity with the vast structural variations in normal hair, the hair growth cycle, and the changes produced by weathering. These structural abnormalities can be congenital or acquired, and some are associated with hair fragility. The classification used here has the advantage of simplicity and is keyed to easy recognition of the abnormalities under the light microscope. The four major types of abnormality are fractures, irregularities, twisting, and extraneous matter affecting the hair shaft. The diagnostic features of the different hair shaft abnormalities are outlined.

Corynebacterium Infections↗
PubMed2005

Dynamic Trees for unsupervised segmentation and matching of image regions.

We present a probabilistic framework--namely, multiscale generative models known as Dynamic Trees (DT)--for unsupervised image segmentation and subsequent matching of segmented regions in a given set of images. Beyond these novel applications of DTs, we propose important additions for this modeling paradigm. First, we introduce a novel DT architecture, where multilayered observable data are incorporated at all scales of the model. Second, we derive a novel probabilistic inference algorithm for DTs--Structured Variational Approximation (SVA)--which explicitly accounts for the statistical dependence of node positions and model structure in the approximate posterior distribution, thereby relaxing poorly justified independence assumptions in previous work. Finally, we propose a similarity measure for matching dynamic-tree models, representing segmented image regions, across images. Our results for several data sets show that DTs are capable of capturing important component-subcomponent relationships among objects and their parts, and that DTs perform well in segmenting images into plausible pixel clusters. We demonstrate the significantly improved properties of the SVA algorithm--both in terms of substantially faster convergence rates and larger approximate posteriors for the inferred models--when compared with competing inference algorithms. Furthermore, results on unsupervised object recognition demonstrate the viability of the proposed similarity measure for matching dynamic-structure statistical models.

Algorithms↗
PubMed1994

Sequence dependence of DNA structure in solution.

Sequence-dependent structural variations in DNA can influence its binding by ligands and proteins. However, relatively little is known about sequence-structure relationship for arbitrary DNA sequences. The 1H two-dimensional NOESY data presented here for ten oligonucleotide duplexes show pronounced sequence-dependent changes in at least two types of internucleotide distances commonly used in sequential connectivity assignments, namely the H-6/H-8 to preceding (5') H-1' distance (S1) and the H-6/H-8 to preceding (5') H-2'' distance (S2). On the basis of these two measured distances, all dinucleotide steps can be divided into four different groups: Y-R, R-Y, R-R and Y-Y, where R is purine and Y is pyrimidine. These data suggest some rules for the variation in these distances along DNA duplexes. Correlations between these distances and helical parameters of DNA are discussed in comparison to well-resolved X-ray structures of B-type DNA.

Base Sequence↗
PubMed1989

Structural and functional characterization of mutants of the bovine leukemia virus transactivator protein p34.

Mutants of the bovine leukemia virus (BLV) transactivator protein (tat, tax, p34, the XLOR gene product) were constructed by site-directed deletions, in-phase linker insertions, or fragment replacements (swapping) among BLV variants. The mutant constructs were transfected into cos cells and transiently expressed. Western blot analysis using a mixture of monoclonal antibodies to wild-type p34 revealed the presence of mutated XLOR gene products in all the mutants tested. The transactivating activity of 11 tax mutants containing site-directed deletions and in-phase linker insertions was completely abolished. Only the swapping mutant tested, a hybrid between two BLV variants, transactivated LTR-directed gene expression at wild-type levels. These data illustrate the narrow range of structural variations that allow full activity of the BLV tax product and suggest that the present molecular structure of the transactivator protein results from heavy evolutionary constraints.

Blotting, Western↗
PubMedDate not supplied

The heavy chain of human B-cell alloantigen HLA-DS has a variable N-terminal region and a constant immunoglobulin-like region.

The HLA-D region of the major histocompatibility complex (MHC) of man encodes polymorphic glycoproteins found predominantly on the cell surfaces of B cells and macrophages. These proteins mediate interactions, required for the induction of immune responses, among cells of the immune system and consequently are referred to as Ia (immune-response associated). Two families of Ia molecules, DR and DS (also known as DC), have been defined, the former analogous to the I-E (ref. 1) and the latter to the I-A molecules of the murine MHC. Both DR and DS molecules consist of two noncovalently associated polypeptide chains with molecular weights of 33,000 and 28,000, designated alpha and beta, respectively. The polymorphism of DR molecules is due to structural variation in the small subunit, DR beta, with the large subunit, DR alpha, being constant in structure. In contrast, both subunits DS alpha and DS beta are structurally variable when DS allotypes are compared. We have now isolated a cDNA clone from a DR7 cell line that contains the entire coding sequence for the DS alpha subunit and have compared its predicted amino acid sequence with that previously deduced from a DS alpha cDNA clone isolated from a DR4,w6 cell line. This comparison reveals that 10 of 11 amino acid differences are located within the alpha 1 (N-terminal) domain and that the alpha 2 or immunoglobulin-like domains are identical.

Amino Acid Sequence↗
PubMed2005

A haplotype map of the human genome.

Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution.

Chromosomes, Human, Y↗
PubMed2000

Negligible genetic diversity of mycobacterium tuberculosis host immune system protein targets: evidence of limited selective pressure.

A common theme in medical microbiology is that the amount of amino acid sequence variation in proteins that are targets of the host immune system greatly exceeds that found in metabolic enzymes or other housekeeping proteins. Twenty-four Mycobacterium tuberculosis genes coding for targets of the host immune system were sequenced in 16 strains representing the breadth of genomic diversity in the species. Of the 24 genes, 19 were invariant and only six polymorphic nucleotide sites were identified in the 5 genes that did have variation. The results document the highly unusual circumstance that prominent M. tuberculosis antigenic proteins have negligible structural variation worldwide. The data are best explained by a combination of three factors: (i) evolutionarily recent global dissemination in humans, (ii) lengthy intracellular quiescence, and (iii) active replication in relatively few fully immunocompetent hosts. The very low level of amino acid diversity in antigenic proteins may be cause for optimism in the difficult fight to control global tuberculosis.

Acyltransferases↗
PubMed2001

Genome screen for quantitative trait loci underlying normal variation in femoral structure.

Femoral structure contributes to bone strength at the proximal femur and predicts hip fracture risk independently of bone mass. Quantitative components of femoral structure are highly heritable traits. To identify genetic loci underlying variation in these structural phenotypes, we conducted an autosomal genome screen in 309 white sister pairs. Seven structural variables were measured from femoral radiographs and used in multipoint sib-pair linkage analyses. Three chromosomal regions were identified with significant evidence of linkage (log10 of the odds ratio [LOD] > 3.6) to at least one femoral structure phenotype. The maximum LOD score of 4.3 was obtained for femur neck axis length on chromosome 5q. Evidence of linkage to chromosome 4q was found with both femur neck axis length (LOD = 3.9) and midfemur width (LOD = 3.5). Significant evidence of linkage also was found to chromosome 17q, with a LOD score of 3.6 for femur head width. Two additional chromosomal regions 3q and 19p gave suggestive (LOD > 2.2) evidence of linkage with at least two of the structure phenotypes. Chromosome 3 showed evidence of linkage with pelvic axis length (LOD = 3.1), midfemur width (LOD = 2.8), and femur head width (LOD = 2.3), spanning a broad (60 cm) region of chromosome 3q. Linkage to chromosome 19 was supported by two phenotypes, femur neck axis length (LOD = 2.8) and femur head width (LOD = 2.8). This study is the first genome screen for loci underlying variation in femoral structure and represents an important step toward identifying genes contributing to the risk of osteoporotic hip fracture in the general population.

Adult↗
PubMed2006

Evaluation of the reduction of imidazophenazine dye derivatives under fast-atom-bombardment mass-spectrometric conditions.

Satellite [M + 2](+*) and [M + 3](+) peaks accompanying the common peak of the protonated molecule [M + H](+) that are known to indicate the occurrence of a reduction process were observed in the fast atom bombardment (FAB) mass spectra of imidazophenazine dye derivatives in glycerol matrix. The distribution of the abundances in the [M + nH](+) peak group varied noticeably for different derivatives. This indicated different levels of the reduction depending on the different structure variations of the studied molecules. In the search for correlations between the mass spectral pattern and the structural features of the dyes, ab initio HF/6-31++G** quantum chemical calculations were performed. They revealed that the abundances of the [M + 2](+*) and [M + 3](+) ions show growth proportional to the decrease of the energy of the lowest unoccupied molecular orbital, i.e. proportional to the increase of the electron affinity of the dye molecule. A method for rapid screening of reductive properties of sets of dye derivatives on the basis of the FAB mass spectral data is discussed.

Journal Article↗
PubMed2001

Enhanced binding of a rationally designed peptide ligand of concanavalin a arises from improved geometrical complementarity.

The structural basis of affinity enhancement was addressed by analyzing the interactions between concanavalin A and the carbohydrate-mimicking peptide ligands. Based on the crystal structures of concanavalin A in complex with these peptides [Jain, D., Kaur, K. J., Sundaravadivel, B., and Salunke, D. M. (2000) J. Biol. Chem. 275, 16098-16102; Jain, D., Kaur, K. J., and Salunke, D. M. (2001) Biophys. J. 80, 2912-2921], a high-affinity analogue was designed. This analogue (acetyl-MYWYPY-amide) binds to the lectin with 32-fold enhanced affinity compared to the corresponding precursor peptides. The crystal structure of concanavalin A bound to the designed peptide has been determined. A peptide molecule binds to each of the crystallographically independent monomers of the tetrameric lectin. The four bound peptide molecules exhibit two major conformations both of which are extended. Unlike in the case of other concanavalin A binding peptides, the structural variations within different conformers of this analogue are marginal. It is apparent that the deletion of the structurally variable region of the larger peptides has led to an improved complementarity and increased buried surface area in the case of the designed peptide. The crystal structure also showed the formation of two backbone hydrogen bonds between the ligand and the ligate which were not present in the complexes of the precursor peptides. The observed structural features adequately explain the enhanced binding of the designed analogue.

Concanavalin A↗
PubMed2003

Monitoring the early steps of unfolding of dicalcium and mono-Ce3+-substituted forms of P43M calbindin D9k.

Early steps of unfolding of P43M Calbindin D(9k) have been evaluated by NMR spectroscopy on the native dicalcium and on the paramagnetic monocerium-substituted derivative. Although at 2 M GdmHCl the protein core maintains its overall folding and structure, amide (15)N R(2) measurements and cross correlation rates between N-H dipole-dipole relaxation and (15)N CSA relaxation reveal a closer and stronger packing of the hydrophobic interactions in the protein as a response to the presence of denaturing agents in solution. A complete reorientation of the Met43 side chain toward the hydrophobic core is accomplished by the disappearance of the millisecond dynamics observed on the native form of Calbindin D(9k), while cross correlation rates provide evidence that the two-way hydrogen bond between Leu23 and Val61 is broken or substantially weakened. The substitution of the calcium ion in site II with the paramagnetic Ce(3+) ion allowed us to obtain a number of long-range nonconventional constraints, namely, pseudocontact shifts, which were used, together with the NOEs collected on the native state, to monitor subtle structural variations occurring in the non-native state of the protein. Although the average rmsd between the structures of native and non-native states is small (0.48 A), structural rearrangements could be reliably identified. Our results provide unprecedented information about the behavior of Calbindin D(9k) during the early steps of unfolding. Furthermore, they constitute strong evidence of the efficiency of paramagnetism-based constraints in monitoring subtle structural changes that are beyond the sensitivity of an approach based only on NOE.

Amides↗
PubMed1999

A new model for the K+-induced macromolecular structure of guanosine 5'-monophosphate in solution.

The (31)P NMR spectra of (TMA)(2)(5'-GMP), where TMA is [(CH(3))(4)N](+) and 5'-GMP is guanosine 5'-monophosphate, and K(2)(5'-GMP), containing various amounts of KCl or TMACl, have been obtained at 2 degrees C. Variable-temperature spectra have also been obtained for K(2)(5'-GMP). The TMA(+) ion serves to neutralize the charge on the dianionic 5'-GMP and permits the added K(+) to bond preferentially in structure-forming sites. (1)H NMR spectra (one- and two-dimensional) have been obtained for K(2)(5'-GMP) and used to assign the proton resonances in the self-associated structures and determine that all residues have the anti glycosidic conformation. The (31)P and (1)H NMR spectra are very complex and indicate the presence of a large number of molecular environments and a structural variation dependent upon the mole ratio of 5'-GMP to K(+). A new model for the solution structure is proposed in which the 5'-GMP forms a pseudo-four-stranded helix with guanine-guanine hydrogen bonding forming a continuous helical strand, rather than the usual planar G-tetrad structure. The guanine-guanine hydrogen bonding sites are the same as that found in a G-tetrad. The K(+) ions would be located in the center of the helix and bonding to the carbonyl oxygens. They are interacting with the phosphates as well. Integration data from the largest sized species give an estimate of 14.3 +/- 1.1 residues in a helical structure.

Cations, Monovalent↗
PubMed2006

Genome sequence alterations detected upon passage of Burkholderia mallei ATCC 23344 in culture and in mammalian hosts.

BACKGROUND: More than 12,000 simple sequence repeats (SSRs) have been identified in the genome of Burkholderia mallei ATCC 23344. As a demonstrated mechanism of phase variation in other pathogenic bacteria, these may function as mutable loci leading to altered protein expression or structure variation. To determine if such alterations are occurring in vivo, the genomes of various single-colony passaged B. mallei ATCC 23344 isolates, one from each source, were sequenced from culture, a mouse, a horse, and two isolates from a single human patient, and the sequence compared to the published B. mallei ATCC 23344 genome sequence. RESULTS: Forty-nine insertions and deletions (indels) were detected at SSRs in the five passaged strains, a majority of which (67.3%) were located within noncoding areas, suggesting that such regions are more tolerant of sequence alterations. Expression profiling of the two human passaged isolates compared to the strain before passage revealed alterations in the mRNA levels of multiple genes when grown in culture. CONCLUSION: These data support the notion that genome variability upon passage is a feature of B. mallei ATCC23344, and that within a host B. mallei generates a diverse population of clones that accumulate genome sequence variation at SSR and other loci.

Animals↗
PubMed1990

Morphological and antigenic variations of human T cell leukemia virus type I particles in human lymphocytes.

HTLV-I particles grown in 4 human lymphocyte cultures were observed by electron microscopy. Particles in all cell lines showed marked size and structural variations that were characteristic of each cell line. Profiles of size-distributions were found to be similar among virus particles of the same origin in different cell lines. Immunogold electron microscopy using monoclonal antibody to HTLV-I-p15, -p19, or -p24 revealed varying reactivities of individual particles. By double-labeling technique using antibody to HTLV-I-p19 or -p24, particles were found to be classifiable into 4 groups: p19+p24+, p19+p24-, p19-p24%, and p19-p24-. Each cell line showed the characteristic profile of distributions of virus particles of each group as observed at different in vitro passage levels. These antibodies reacted with certain structures in the extracellular space and in the cytoplasm. Results of this study demonstrate variations in morphology and antigenicity, as well as the morphogenesis of HTLV-I particles in different host cells.

Cell Line↗
PubMed2002

Magnetic resonance imaging of normal and osteoarthritic trabecular bone structure in the human knee.

OBJECTIVE: To use high-resolution magnetic resonance imaging (MRI) to evaluate the trabecular bone structure in the distal femur and the proximal tibia and its to correlate the findings with different stages of osteoarthritis (OA) of the human knee. METHODS: Axial images of the distal femur and proximal tibia were obtained at 1.5 T in patients without and with mild OA and with severe OA. The spatial resolution was 195 x 195 microm(2) with a 1-mm slice thickness. Apparent measures of trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular separation (Tb.Sp), and trabecular thickness (Tb.Th) were calculated. RESULTS: Significant differences existed in the trabecular bone structure of the femur and tibia. Differences in trabecular bone structure between the tibia and the femur decreased with the degree of OA. The apparent BV/TV, Tb.N, and Tb.Sp in the femoral condyles could be used to differentiate healthy patients or patients with mild OA from patients with severe OA (P < 0.05). Among individuals, the structural variation of the lateral and medial femoral condyle was indicative of the extent of the disease. CONCLUSION: High-resolution MRI of the knee joint can provide a noninvasive assessment of trabecular bone structure. Trabecular bone structure, determined by high-resolution MRI, shows significant variation in patients with varying degrees of OA. The impact of OA on trabecular bone is different in the tibia than in the femur, and this difference depends on the extent of the disease.

Adult↗