The muscarinic receptor binding of trazodone, a new nontricyclic antidepressant, was compared with established tricyclic antidepressants. The ability to inhibit the binding of [3H]-quinuclidinyl benzilate...Full Text Available
SummaryMammalian iron homeostasis is regulated by the interaction of the liver-produced peptide hepcidin and its receptor, the iron transporter ferroportin. Hepcidin binds to...Full Text Available
The bindinginteractions of four ligands differing in acid-base properties with human serum albumin (HSA) were examined as a function of temperature. Binding to HSA decreased with increasing temperature...Full Text Available
Albumin is a multifunctional transport protein that binds a wide variety of endogenous substances and drugs. Insulins with affinity for albumin were engineered by acylation of the epsilon-amino group...Full Text Available
The adenovirus fiber knob causes the first step in the interaction of adenovirus with cell membrane receptors. To obtain information on the receptor binding site(s), the interaction of labeled cell...Full Text Available
I propose that an interpretation of the interaction of noble gas atoms with metal surfaces as predominantly physisorbing provides the best explanation for the systematics of their binding energies and surface dipoles, as well as for the tendency of noble gas atoms to bind in low coordinated sites. In the present context physisorption is defined as a process driven by the overlap of the electrostatic atomic potentials of the interacting species. (orig.)
A study was made of the kinetics of L-(/sup 3/H)quinuclidinyl benzilate binding with membrane-bound muscarine cholinoreceptors from the rat brain. Determination was made of the rate constants of this process, and constants as a function of ligand concentration was investigated, indicating that there is a complex mechanism of interaction of antagonists with muscarine receptor. With up to 3.5 nM concentrations of L-(/sup 3/H)quinuclidinyl benzilate, the binding reaction occurs in two stages: rapid equilibrated binding is followed by a slow process of conformational isomerization of the receptor-ligand complex. At higher ligand concentrations, there is additional drastic increase in constant of rate of ligand binding a new plateau is reached. Such dependence of rate constant on ligand concentration is indicative of the cooperative nature of interaction between ...
Binding of Cd/sup 2 +/ ions in aqueous solutions of statistical copolymers of acrylamide with cadmium acrylate with different content of ionogenic groups in copolymers was investigated by polarography, conductometry, viscometry and dialysis. It is shown that the degree of binding of Cd/sup 2 +/ ions increases with increasing of the content of ionogenic groups in the copolymer and with decreasing of ionic strength of the solution. The values of the degree of binding of Cd/sup 2 +/ ions obtained by polarography and dialysis show satisfactory agreement.
The interactions of flavonoid, quercetin with sodium dodecyl sulfate (anionic surfactant) and cetyltrimethyl ammonium bromide (cationic surfactant) micelles were investigated. The average location site of quercetin in different micelles was determined by the cyclic voltammetry method with the aid of molecular optimization. The interaction parameters of quercetin with micelles of different charges such as binding constant K and normal binding energy DG were calculated. Furthermore, the morphologic change of the SDS and CTAB spherical micelles and rod-like micelles upon their interaction with quercetin was also observed.
Gel filtration of human erythrocyte (RBC) lysate incubated with labeled thyroxine (Tu) or triiodothyronine (Tt) revealed co-elution of a major iodothyronine-binding fraction (R-2) and hemoglobin. Solutions of purified human hemoglobin and Tt also showed co-elution of hormone and hemoglobin. Because hematin and protoporphyrin were shown to bind labeled Tt, the oxygen-binding site on hemoglobin was excluded as the site of iodothyronine-hemoglobin interaction. Analysis of hormone binding by heme and globin moieties showed Tt binding to be limited to the heme fraction. Addition of excess unlabeled Tt to hemoglobin or heme incubated with labeled Tt indicated 75% to 90% of hormone binding was poorly dissociable. These observations suggested that the presence of hemoglobin in RBC lysate or in serum could influence the measurement of Tu and Tt by ...
The solvation properties of a chlorine ion in small water clusters are investigated using state-of-the-art statistical mechanics. The simulations employ the polarizable water model developed recently by Dang [J. Chem. Phys. [bold 97], 2659 (1992)]. The ion--water interaction potentials are defined such that the successive binding energies for the ionic clusters, and the solvation enthalpy, bulk vertical binding energy, and structural properties of the aqueous solution agree with the best available results obtained from experiments. Simulated vertical electron binding energies of the ionic clusters Cl[sup [minus
Transforming growth factor (TGF)-βs are secreted in large latent complexes consisting of TGF-β, its N-terminal latency-associated peptide (LAP) propeptide, and latent TGF-β...Full Text Available
The retina-specific ATP-binding cassette (ABC) transporter, ABCA4, is essential for transport of all-trans-retinal from the rod outer segment discs in the retina and is associated with...Full Text Available
CBP and its paralog p300 are histone acetyl transferases that regulate gene expression by interacting with multiple transcription factors via specialized domains. The structure...Full Text Available
The characterization of the single-chain protein in Chinese-cobra (Naja naja atra) blood serum, which yields strong specific protection against the venom of the same snake, is reported. The protein,...Full Text Available
The parathyroid hormone receptor (PTHR) is a class B G protein-coupled receptor that plays critical roles in bone and mineral ion metabolism. Ligand binding to the PTHR involves interactions to both...Full Text Available
A variety of albumin polymers were prepared and tested for binding with hepatitis B surface antigen (HBsAg): synthetic polymers cross-linked by either glutaraldehyde or carbodiimide; heat-aggregated...Full Text Available
BackgroundThe VP2 outer capsid protein Bluetongue Virus (BTV) is responsible for receptor binding, haemagglutination and eliciting host-specific immunity. However, the assembly of...Full Text Available
BackgroundProteins may evolve through the recruitment and modification of discrete domains, and in many cases, protein action can be dissected at the domain level. PDZ domains are...Full Text Available
Cell surface glycosaminoglycans play important roles in cell adhesion and viral entry. Laboratory strains of two alphaviruses, Sindbis and Semliki Forest virus, have been shown to utilize heparan sulfate as an attachment receptor, whereas Ross River virus (RRV) does not significantly interact with it. However, a single amino acid substitution at residue 218 in the RRV E2 glycoprotein adapts the virus to heparan sulfate binding and expands the host range of the virus into chicken embryo fibroblasts. Structures of the RRV mutant, E2 N218R, and its complex with heparin were determined through the use of electron cryo-microscopy and image reconstruction methods. Heparin was found to bind at the distal end of the RRV spikes, in a region of the E2 glycoprotein that has been previously implicated in cell-receptor recognition and antibody binding.
Synaptobrevin is a synaptic vesicle protein that has an essential role in exocytosis and forms the SNARE complex with syntaxin and SNAP-25. We have analyzed the structure of isolated synaptobrevin and its binary interaction with syntaxin using NMR spectroscopy. Our results demonstrate that isolated synaptobrevin is largely unfolded in solution. The entire SNARE motif of synaptobrevin is capable of interacting with the isolated C-terminal SNARE motif of syntaxin but only a few residues bind to the full-length cytoplasmic region of syntaxin. This result suggests an interaction between the N- and C-terminal regions of syntaxin that competes with core complex assembly.
A relatively quick and simple assay for hyaluronate was developed using the specific binding protein, hyaluronectin. The hyaluronectin was obtained by homogenizing the brains of Sprague-Dawley rats, and then centrifuging the homogenate. The resulting supernatant was used as a source of crude hyaluronectin. In the binding assay, the hyaluronectin was mixed with (/sup 3/H)hyaluronate, followed by an equal volume of saturated (NH/sub 4/)/sub 2/SO/sub 4/, which precipitated the hyaluronectin and any (/sup 3/H)hyaluronate associated with it, but left free (/sup 3/H)hyaluronate in solution. The mixture was then centrifuged, and the amount of bound (/sup 3/H)hyaluronate in the precipitate was determined. Using this assay, the authors found that hyaluronectin specifically bound hyaluronate, since other glycosaminoglycans failed to compete for the binding protein. In addition, the interaction between ...
The E6 oncoproteins of high-risk human papillomaviruses provide important functions not only for malignant transformation but also in the productive viral life cycle. E6 proteins have been shown to bind to a number of cellular factors, but only a limited number of analyses have investigated the effects of these interactions on the viral life cycle. In this study, we investigated the consequences of HPV 31 E6 binding to E6TP1, a putative Rap1 GAP protein. HPV 16 E6 has been shown to bind as well as induce the rapid turnover of E6TP1, and similar effects were observed with HPV 31 E6. Mutation of amino acid 128 in HPV 31 E6 was found to abrogate the ability to bind and degrade E6TP1 but did not alter binding to another ?-helical domain protein, E6AP. When HPV 31 genomes containing mutations a...
We study two correlated electrons in a nearest-neighbour tight-binding chain, with both on-site and nearest-neighbour interaction. Both the cases of parallel and antiparallel spin are considered. In addition to the free electron band for two electrons, there are correlated bands with positive or negative energy, depending on whether the interaction parameters are repulsive or attractive. Electrons form bound states, with amplitudes that decay exponentially with separation. Conditions for such states to be filled at low temperatures are discussed.
Sequence-specific interactions between aminoacyl-tRNA synthetases and their cognate tRNAs both ensure accurate RNA recognition and prevent the binding of noncognate substrates. Here we show for Escherichia...Full Text Available
High-resolution "1H and "3"1P nuclear magnetic resonance spectroscopy has been used to investigate the binding of 2,3-diphosphoglycerate to human normal adult hemoglobin and the molecular interactions involved in the allosteric effect of the 2,3-diphosphoglycerate molecule on hemoglobin. Individual hydrogen ion NMR titration curves have been obtained for 22-26 histidyl residues of hemoglobin and for each phosphate group of 2,3-diphosphoglycerate with hemoglobin in both the deoxy and carbonmonoxy forms. The results indicate that 2,3-diphosphoglycerate binds to deoxyhemoglobin at the central cavity between the two #beta# chains and the binding involves the #beta#2-histidyl residues. Moreover, the results suggest that the binding site of 2,3-diphosphoglycerate to carbonmonoxyhemoglobin contains the same (or at least some of the same) amino acid residues responsible for ...
The authors used radioligand binding and studies of cell contraction to characterize muscarinic receptors on dispersed smooth muscle cells from rabbit proximal and distal colon. Cells obtained after serial incubations in collagenase were used to measure binding of tritiated quinuclidinyl benzilate (["3H]QNB). At 37 degree C, specific ["3H]QNB binding was saturable and linearly related to cell number. Nonlinear regression analysis was used to determine the affinity of ["3H]QNB for its receptor. The IC_5_0 for the muscarinic agonists bethanechol and oxotremorine were 80 and 0.57 #mu#M, respectively. Hill coefficients were 0.67 for both, suggesting more complex interaction involving receptors of different affinities. In studies of cell contraction, bethanechol stimulated a dose-dependent decrease in cell length with half the maximal contraction occurring at 100 pM. These results suggest that (1) ...
Abstract Hydrogen bonding interactions between amino acids and nucleic acid bases constitute the most important interactions responsible for the specificity of protein binding. In this study, complexes formed by hydrogen bonding interactions between cysteine and thymine have been studied by density functional theory. The relevant geometries, energies, and IR characteristics of hydrogen bonds (H-bonds) have been systematically investigated. The quantum theory of atoms in molecule and natural bond orbital analysis have also been applied to understand the nature of the hydrogen bonding interactions in complexes. More than 10 kinds of H-bonds including intra- and intermolecular H-bonds have been found in complexes. Most of intermolecular H-bonds involve O (or N) atom as H-acceptor, whereas the...
A hyaluronic acid binding fraction was purified from the supernatant media of both 3T3 and murine sarcoma virus (MSV) transformed 3T3 cultures by hyaluronate and immunoaffinity chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis resolved the hyaluronate affinity-purified fraction into three major protein bands of estimated molecular weight (M/sub r,e/) 70K, 66K, and 56K which contained hyaluronate binding activity and which were termed hyaluronate binding proteins (HABP). Hyaluronate affinity chromatography combined with immunoaffinity chromatography, using antibody directed against the larger HABP, allowed a 20-fold purification of HABP. Fractions isolated from 3T3 supernatant medium also contained additional binding molecules in the molecular weight range of 20K. This material was present in vanishingly small amounts and was not detected with a silver stain or with (/sup ...
Purpose To study the activation and expression of vascular (aorta and small mesenteric arteries) potassium channels during septic shock with or without modulation of the NO pathway. Methods Septic shock was induced in rats by peritonitis. Selective inhibitors of vascular KATP (PNU-37883A) or BKCa [iberiotoxin (IbTX)] channels were used to demonstrate their involvement in vascular hyporeactivity. Vascular response to phenylephrine was measured on aorta and small mesenteric arteries mounted on a wire myograph. Vascular expression of potassium channels was studied by PCR and Western blot, in the presence or absence of 1400W, an inducible NO synthase (iNOS) inhibitor. Aortic activation of the transcriptional factor nuclear factor-kappaB (NF-?B) was assessed by electrophoretic mobility shift as...
Interactions between cationic dye-cationic surfactant and anionic dye-cationic surfactant systems were investigated in aqueous solutions using spectrophotometric method at 288.15, 298.15, 308.15 and 318.15K. C.I. Basic Red 9 (BR9) and C.I. Acid Blue 25 (AB25) were used as cationic and anionic dyes, respectively, and hexadecyltrimethylammonium bromide (HDTMABr) was selected as cationic surfactant in this study. Although there was an interaction between the AB25 and the HDTMABr molecules, an interaction between the BR9 and HDTMABr did not occur due to the electrostatic repulsion forces. Binding constants and partition coefficients between the micellar and the bulk water phases for the AB25-HDTMABr system were calculated from the changes in absorbance values and the critical micelle concentra...
In the present study, the authors examine the interactions of pentavalent technetium ions (TcO/sup 3+/) with the basic form of the lasalocid A in pure methanol solvent and in methanol-water mixtures. There are a number of reasons for such a study. First, the interactions of technetium ions with biologically important compounds are of considerable importance owing to the widespread use of /sup 99m/Tc in diagnostic radio-imaging. Second, lasalocid A is known to transport metal ions across phospholipid bilayer membranes and between the aqueous cores of phospholipid inverse micelles. Third, lasalocid A is known to bind and solubilize metal ions in bulk organic liquid phases. Fourth, the conformation adopted by lasalocid A on interaction with TcO/sup 3+/ appears to be different than those found in most other cases and circumstances. Fifth, it may also be possible to use the competition of TcO/sup 3+/ with ...
Regulation of transcription initiation by RNA polymerase II requires TFIID, a multisubunit complex composed of the TATA binding protein (TBP) and at least seven tightly associated factors (TAFs). Some TAFs act as direct targets or coactivators for promoter-specific activators while others serve as interfaces for TAF-TAF interactions. Here, we report the molecular cloning, expression and characterization of Drosophila dTAFII60 and its human homolog, hTAFII70. Recombinant TAFII60/70 binds weakly to TBP and tightly to the largest subunit of TFIID, TAFII250. In the presence of TAFII60/70, TBP and TAFII250, a stable ternary complex is formed. Both the human and Drosophila proteins directly interact with another TFIID subunit, dTAFII40. Our findings reveal that Drosophila TAFII60 and human TAFII70 share a high degree of structural similarity and that their interactions with other subunits ...
The parmbsc0 force field was applied to study in detail the binding of netropsin, at a salt concentration of 0.28M Na^+, to the minor groove of an 8-mer (5'CCAATTGG)2 DNA duplex forming a netropsin.DNA complex which previously has been characterized by X-ray crystallography, albeit with the use of closely related DNA duplexes. The X-ray structure revealed that the terminal guanidinium and amidinium groups of netropsin interact with the extreme ends of the palindromic AATT sequence of the receptor DNA. The parmbsc0 parameters of B-DNA and AMBER v9 parameters of netropsin generated a stable 6ns molecular dynamics (MD) trajectory for a 1:1 class I binding motif of this complex. Trajectory analysis for the salt and hydration effects on the binding of netropsin to the 8-mer DNA duplex revealed ...
A high sensitivity (titer 60-150,000) radioimmunoassay for arginine vasopressin (AVP) has been developed using synthetic AVP as antigen and standard. The specificity of the antiserum has been characterized in detail by measuring the relative binding affinities of 29 analogs and fragments of AVP. In general, single amino acid substitution or deletion in the AVP molecule caused a reduction in binding to the antiserum; binding was further impaired for analogs which had multiple substitutions. ''Ring'' and ''tail'' fragments of the neurohypophysial hormones did not bind to the antiserum, and the only analog which the antiserum could not differentiate from AVP was deamino-AVP. More specifically, the antiserum exhibited the following properties: position 1, no requirement for a position charge at "1/_2 Cys; positions 2 and 3, requirements for #pi#-#pi# interacting pair of aromatic side ...
The cell cycle-regulatory transcription factor E2F-1 is regulated by interactions with proteins such as the retinoblastoma gene product and by cell cycle-dependent alterations in E2F-1 mRNA abundance....Full Text Available
Intimin facilitates intestinal colonization by enterohemorrhagic Escherichia coli O157:H7; however, the importance of intimin binding to its translocated receptor (Tir) as opposed to...Full Text Available
Peroxisome proliferator activated receptor-{gamma} (PPAR{gamma}) regulates metabolic homeostasis and adipocyte differentiation, and it is activated by oxidized and nitrated fatty acids. Here we report the crystal structure of the PPAR{gamma} ligand binding domain bound to nitrated linoleic acid, a potent endogenous ligand of PPAR{gamma}. Structural and functional studies of receptor-ligand interactions reveal the molecular basis of PPAR{gamma} discrimination of various naturally occurring fatty acid derivatives.
Most antibodies to factor VIII have recently been shown to react with discrete regions of the factor VIII light chain (within the C2 domain) and/or the factor VIII heavy chain (within the amino-terminal...Full Text Available
Within the tight binding framework, a study is made of how the disorder affects the electronic properties of A-15 compounds. In particular it is shown that for compounds of two transition metals in the A-15 structure, the vacancy formation affects the density of states only in the low energy region or in the high energy region, in opposition with the isolated chain model of Labbe and Friedel. It is concluded that interchain interactions are important. (U.K.).
The nature of binding of Ru(phen) 2+ (I), Ru(bipy) 2+ (II), Ru(terpy) 2+ (III) (phen = 1,10-phenanthroline, bipy 3 = 2,2'-bipyridyl, 3 terpy = 2,2'2," - 2 terpyridyl) to DNA, poly[d(G-C)] and poly[d(A-T)]...Full Text Available
S100A4, a member of the Ca(2+)-activated S100 protein family, regulates the motility and invasiveness of cancer cells. Moreover, high S100A4 expression levels correlate with poor patient survival in several cancers. Although biochemical, biophysical, and structural data indicate that S100A4 is a noncovalent dimer, it is unknown if two functional S100A4 monomers are required for the productive recognition of protein targets and the promotion of cell invasion. To address this question, we created covalently linked S100A4 dimers using a glycine rich flexible linker. The single-chain S100A4 (sc-S100A4) proteins exhibited wild-type affinities for calcium and nonmuscle myosin-IIA, retained the ability to regulate nonmuscle myosin-IIA assembly, and promoted tumor cell invasion when expressed in S100A4-deficient colon carcinoma cells. Mutation of the two calcium-binding EF-hands in one monomer, while leaving the other monomer intact, caused a 30-60-fold reduction in ...
Crystallography and computer modeling have been used to exploit a previously unexplored channel in the glucocorticoid receptor (GR). Highly potent, nonsteroidal indazole amides showing excellent complementarity to the channel were designed with the assistance of the computational technique AlleGrow. The accuracy of the design process was demonstrated through crystallographic structural determination of the GR ligand-binding domain-agonist complex of the D-prolinamide derivative 11. The utility of the channel was further exemplified through the design of a potent phenylindazole in which structural motifs, seen to interact with the traditional GR ligand pocket, were abandoned and replaced by interactions within the new channel. Occupation of the channel was confirmed with a second GR crystal structure of this truncated D-alaninamide derivative 13. Compound 11 displays properties compatible with development as an intranasal ...
This paper describes the search for new potential chemotherapeutic agents based on transition metal complexes with planar ligands. In this study, palladium polypyridyl complexes were synthesized and characterized by elemental analysis, NMR, UV-VIS and IR spectroscopies. The interaction of the complexes with DNA was also investigated by spectroscopic methods. All metal-to-ligand charge transfer (MLCT) bands of the palladium polypyridyl complexes exhibited hypochromism and red shift in the presence of DNA. The binding constant and viscosity data suggested that the complexes [PdCl{sub 2}(phen)] and [PdCl{sub 2}(phendiamine)] interact with DNA by electrostatic forces. Additionally, these complexes induced an important leishmanistatic effect on L. (L.) mexicana promastigotes at the final concentration of 10 {mu}mol L{sup -1} in 48 h. (author)
The class of Spirochetes comprises a wide array of clinically important pathogens, including Treponema pallidum causing syphilis as well as Borrelia burgdorferi, the agent of Lyme disease (LD). Diseases caused by spirochetes are characterized by specific sequelae of host reactions, and also by characteristic antibody response patterns. Over the last decades, research on the interaction of spirochetes with the hosts immune system had a strong emphasis on outer membrane lipoproteins. In fact, these structures have been convincingly shown to activate immune cells via CD14 and Toll-like receptor (TLR)-2, and recent data also indicate an interaction with lipopolysaccharide (LPS)-binding protein (LBP). In particular, the interaction of B. burgdorferi with TLR-2 could not only be demonstrated in ...
It is known that the plant cuticle represents the first barrier that must be overcome by any chemical reaching the plant surface from the atmosphere before entering the plant. Because of the importance of the cuticle as a barrier to penetration of a wide variety of compounds, its morphology, chemistry, and permeability have been extensively studied. However, only limited information is available on the nature of functional chemical groups present and their interaction and role during the penetration process. The usefulness of in situ Fourier transform infrared spectroscopy studies in identifying functional groups present in isolated cuticles is described and their relationships to the structure of the cuticular membrane are discussed. Applications of infrared spectroscopy on the presence and role of phenolics in the cuticle structure and during the cuticle development, nitrogen oxide binding to isolated cuticles, and the ...
The functional interaction between the peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) and its coactivator PGC-1{alpha} is crucial for the normal physiology of PPAR{gamma} and its pharmacological response to antidiabetic treatment with rosiglitazone. Here we report the crystal structure of the PPAR{gamma} ligand-binding domain bound to rosiglitazone and to a large PGC-1{alpha} fragment that contains two LXXLL-related motifs. The structure reveals critical contacts mediated through the first LXXLL motif of PGC-1{alpha} and the PPAR{gamma} coactivator binding site. Through a combination of biochemical and structural studies, we demonstrate that the first LXXLL motif is the most potent among all nuclear receptor coactivator motifs tested, and only this motif of the two LXXLL-related motifs in PGC-1{alpha} is capable of binding to PPAR{gamma}. Our studies reveal that the strong ...
The anticonvulsant drugs carbamazepine, phenobarbital, trimethadione, valproic acid and ethosuximide at pharmacologically relevant concentrations inhibit (/sup 3/H)diazepam binding to astrocytes in primary cultures but have much less effect on a corresponding preparation of neurons. Phenytoin as well as pentobarbital (which is not used chronically as an anticonvulsant) are equipotent in the two cell types. The convulsants picrotoxinin and pentylenetetrazol, the convulsant benzodiazepine RO 5-3663 and the two convulsant barbiturates DMBB and CHEB similarly inhibit diazepam binding to astrocytes but have little effect on neurons. On the basis of these findings it is suggested that these convulsants and anticonvulsants owe at least part of their effect to an interaction with the astrocytic benzodiazepine receptor, perhaps by interference with a calcium channel.
In a sufficiently large cluster of several polar molecules, collective interactions lead to localization or 'solvation' of electrons. The existence of the solvated electron is known since 1863 in liquid ammonia and since 1962 for liquid water. In 1984, electron localization in clusters was experimentally demonstrated in (H_2O)_N_#>=#_1_1 and (NH_3)_N_#>=#_3_4 clusters. In cooperation with K. Bowen, we recently initiated a test of the theory of electron binding by a dipole and a new ground state dipole bound dimer anion, (H_2O..NH_3), was predicted and observed. We here describe results of a search for new dipole-bound and solvated electron systems. (author).
Myostatin is a member of the transforming growth factor-{beta} (TGF-{beta}) family and a strong negative regulator of muscle growth. Here, we present the crystal structure of myostatin in complex with the antagonist follistatin 288 (Fst288). We find that the prehelix region of myostatin very closely resembles that of TGF-{beta} class members and that this region alone can be swapped into activin A to confer signalling through the non-canonical type I receptor Alk5. Furthermore, the N-terminal domain of Fst288 undergoes conformational rearrangements to bind myostatin and likely acts as a site of specificity for the antagonist. In addition, a unique continuous electropositive surface is created when myostatin binds Fst288, which significantly increases the affinity for heparin. This translates into stronger interactions with the cell surface and enhanced myostatin degradation in the presence of either Fst288 or Fst315. ...
We recently found that many RNA polymerase II transcription factors are modified with N-acetylglucosamine residues. These sugar moieties confer upon transcription factors an ability to bind the lectin wheat germ agglutinin. We have taken advantage of this interaction to devise a purification procedure for the "GC-box" binding transcription factor Sp1. Crude nuclear extracts are first subjected to wheat germ agglutinin affinity chromatography and then subjected to sequence-specific DNA affinity chromatography. The Sp1 protein purified by this procedure is at least 95% pure, and the overall recovery is greater than 80%. In addition to yielding larger quantities of Sp1 than conventional schemes, the new purification procedure is also simpler and more rapid. We show that wheat germ agglutinin affinity chromatography can also be used to purify the glycosylated forms of the CCAAT-binding transcription factor. ...
Transcriptional regulation of the galactose-metabolizing genes in Saccharomyces cerevisiae depends on three core proteins: Gal4p, the transcriptional activator that binds to upstream activating DNA sequences (UASGAL); Gal80p, a repressor that binds to the carboxyl terminus of Gal4p and inhibits transcription; and Gal3p, a cytoplasmic transducer that, upon binding galactose and adenosine 5'-triphosphate, relieves Gal80p repression. The current model of induction relies on Gal3p sequestering Gal80p in the cytoplasm. However, the rapid induction of this system implies that there is a missing factor. Our structure of Gal80p in complex with a peptide from the carboxyl-terminal activation domain of Gal4p reveals the existence of a dinucleotide that mediates the interaction between the two. Biochemical and in vivo experiments suggests that nicotinamide adenine dinucleotide phosphate (NADP) plays a key ...
The GTPases comprise a protein superfamily of highly conserved molecular switches adapted to many diverse functions. These proteins are found in all domains of life and often perform essential roles in fundamental cellular processes. Analysis of data from genome sequencing projects demonstrates that bacteria possess a core of 11 universally conserved GTPases (elongation factor G and Tu, initiation factor 2, LepA, Era, Obg, ThdF/TrmE, Ffh, FtsY, EngA and YchF). Investigations aimed at understanding the function of GTPases indicate that a second conserved feature of these proteins is that they elicit their function through interaction with RNA and/or ribosomes. An emerging concept suggests that the 11 universal GTPases are either necessary for ribosome function or transmitting information from the ribosome to downstream targets for the purpose of generating specific cellular responses. Furthermore, it is suggested that progenitor GTPases were early regulators of RNA ...
Phosphoenolpyruvate carboxykinase (GTP) (PEPCK) specifically utilizes a guanosine or inosine nucleotide as a substrate, yet it does not share extended sequence homology with other GTP-binding proteins, and the molecular basis for its nucleotide specificity is not understood. In an effort to locate the enzyme's nucleotide-binding site, the authors have studied the interaction of cytosolic PEPCK from rat liver with the photoprobe 8-azidoGTP, which fulfills the criteria of a specific photoaffinity label for PEPCK. The photoprobe binds reversibly to the enzyme prior to modification and at low concentrations causes greater than 60% inactivation-GTP provides nearly complete protection against inactivation by 8-azidoGTP, whereas phosphoenolpyruvate and metal ions provide partial protection. In addition, the photoprobe is a substrate for the enzyme and has a K_m similar to that for GTP. However, the extent of ...
Phosphoenolpyruvate carboxykinase (GTP) (PEPCK) specifically utilizes a guanosine or inosine nucleotide as a substrate, yet it does not share extended sequence homology with other GTP-binding proteins, and the molecular basis for its nucleotide specificity is not understood. In an effort to locate the enzyme's nucleotide-binding site, the authors have studied the interaction of cytosolic PEPCK from rat liver with the photoprobe 8-azidoGTP, which fulfills the criteria of a specific photoaffinity label for PEPCK. The photoprobe binds reversibly to the enzyme prior to modification and at low concentrations causes greater than 60% inactivation-GTP provides nearly complete protection against inactivation by 8-azidoGTP, whereas phosphoenolpyruvate and metal ions provide partial protection. In addition, the photoprobe is a substrate for the enzyme and has a K{sub m} similar to that for GTP. However, ...
..cap alpha..-2 adrenergic agents have been shown to influence blood pressure, heart rate and other physiological and behavioral functions through interactions with adrenergic pathways within the central nervous system. Pharmacologically relevant ..cap alpha..-1 adrenergic receptors were biochemically characterized and radiohistochemically analyzed in intact tissue sections of the rat and human central nervous system. The anatomical distribution of the ..cap alpha..-2 receptors, labeled with the agonist (/sup 3/H)para-aminoclonidine, verified the concept that ..cap alpha..-2 receptors are closely associated with adrenergic nerve terminals and that ..cap alpha..-2 agents can influence autonomic and endocrine function through an action in the central nervous system. Since ..cap alpha..-2 agonists can influence sympathetic outflow, ..cap alpha..-2 binding sites were closely analyzed in the intermediolateral cell column of the thoracic spinal cord. ...
The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) has two major functions: interacting with the receptor to mediate virus entry and inducing protective immunity. Coincidently, the receptor-binding domain (RBD, residues 318-510) of SAR-CoV S protein is a major antigenic site to induce neutralizing antibodies. Here, we used RBD-Fc, a fusion protein containing the RBD and human IgG1 Fc, as a model in the studies and found that a single amino acid substitution in the RBD (R441A) could abolish the immunogenicity of RBD to induce neutralizing antibodies in immunized mice and rabbits. With a panel of anti-RBD mAbs as probes, we observed that R441A substitution was able to disrupt the majority of neutralizing epitopes in the RBD, suggesting that this residue is critical for the antigenic structure responsible for inducing protective immune responses. We also demonstrated that the RBD-Fc bearing R441A mutation could not ...
A comparative study on the interaction of different PEG-containing diblock copolymers including SA400, SA600, SA1500 and OA1500 (stearyl and oleyl esters of polyethylene glycol with 400, 600 and 1500 molecular weights, respectively) with bovine serum albumin (BSA) was carried out using isothermal titration calorimetry (ITC), attenuated total reflectance Fourier transform infrared (ATR-FTIR), circular dichroism (CD), and fluorescence spectroscopies. ITC data show that SA400, SA600, SA1500 and OA1500 bind to BSA, with association constants of (14.5, 3.16, 50.7 and 17.6)x103M-1, respectively. Results also show that the binding is enthalpically driven, disfavored by conformational entropy. Quantitative analysis of the FTIR absorbance spectra at amide Iprime (1600-1700cm-1) as well as far UV ci...
High-resolution proton nuclear magnetic resonance spectroscopy has been used to investigate the molecular mechanism of the Bohr effect of human normal adult hemoglobin in the presence of two allosteric effectors, i.e., chloride and inorganic phosphate ions. The individual hydrogen ion equilibria of 22-26 histidyl residues of hemoglobin have been measured in anion-free 0.1 M HEPES buffer and in the presence of 0.18 M chloride or 0.1 M inorganic phosphate ions in both deoxy and carbonmonoxy forms. The results indicate that the #beta#2-histidyl residues are strong binding sites for chloride and inorganic phosphate ions in hemoglobin. The affinity of the #beta#2-histidyl residues for these anions is larger in the deoxy than in the carbonmonoxy form. Nevertheless, the contribution of these histidyl residues to the anion Bohr effect is small due to their low pK value in deoxyhemoglobin in anion-free solvents. The interactions of chloride and ...
The pole trajectory of Efimov states for a three-body ??? system with ?? unbound and ?? bound is calculated using a zero-range Dirac-? potential. It is shown that a three-body bound state turns into a virtual one by increasing the ?? binding energy. This result is consistent with previous results for three equal mass particles. The present approach considers the n-n-18C halo nucleus. However, the results have good perspective to be tested and applied in ultracold atomic systems, where one can realize such three-body configuration with tunable two-body interaction. Presented at the 20th Few-Body Conference, Pisa, Italy, 10-14 September 2007. (author)
Progress in calculating the electron-phonon parameters of transition metals has been based on either the rigid muffin-tin approximation (RMTA) or the fitted modified tight-binding approximation (FMTBA). The RMTA has been shown to be remarkably accurate for average electron-phonon properties, but there are indications that RMTA matrix elements may be too small at low momentum transfer. An attempt is made to demonstrate these assertions concerning the accuracy of RMTA and the numerous electron-phonon calculations are placed in a broader perspective by a demonstration of how they can be used to explain the trends in the strength of the electron-phonon coupling among the transition metals and the A-15 compounds. (GHT)
The tet repressor regulated expression of the Tn-10-encoded tetracycline resistance determinant in a tetracycline-dependent manner. In the absence of tetracycline, the tet repressor binds as a dimer to the 19-base-pair palindromic tet operator sequence. Amino acid homologies and genetic studies with trans-dominant mutants suggest that sequence-specific recognition of the tet operator involves the extensively studied helix-turn-helix motif. We have used the uracil-DNA glycosylase (UDG) footprinting systems to identify thymine contacts in the tet operator that are essential for the formation of tet repressor-operator complexes.
Photobilirubin II, a stereoisomer of bilirubin, binds to human serum albumin at a single binding site (K = 2.2 x 10(6)M-1), presumably the high-affinity bilirubin-binding site. Binding in the secondary...Full Text Available
A new two-body interaction recently derived for nuclei in the 0f1p shell by fitting two-body matrix elements to 494 energy levels in A=41-66 nuclei, is used to investigate the neutron-rich nuclei in the vicinity of the doubly closed nuclide {sup 48}Ca. This study is of fundamental interest in providing a test for the new effective interaction away from the stability line. Masses and binding energies are calculated for a variety of neutron-rich nuclei and compared with experimental data, where available. In addition level schemes for {sup 50-52}Ca, {sup 51-52}Sc and {sup 51-52}Ti have been calculated and are compared with available experimental data. In general a good correspondence between theory and experiment is found, but some systematic discrepancies are apparent. ((orig.)).
A new two-body interaction recently derived for nuclei in the 0f1p shell by fitting two-body matrix elements to 494 energy levels in A=41-66 nuclei, is used to investigate the neutron-rich nuclei in the vicinity of the doubly closed nuclide "4"8Ca. This study is of fundamental interest in providing a test for the new effective interaction away from the stability line. Masses and binding energies are calculated for a variety of neutron-rich nuclei and compared with experimental data, where available. In addition level schemes for "5"0"-"5"2Ca, "5"1"-"5"2Sc and "5"1"-"5"2Ti have been calculated and are compared with available experimental data. In general a good correspondence between theory and experiment is found, but some systematic discrepancies are apparent. ((orig.)).
A comparative study on the interaction of (PEG-co-P(FA/SC)-co-PEG) triblock copolymer with bovine and human insulins was carried out using isothermal titration calorimetry (ITC), circular dichroism (CD), and fluorescence spectroscopy. ITC data show that the copolymer has a low affinity for both proteins, with an association constant of about 7?9?103?M ?1. Results also show that binding is enthalpically driven, and disfavored by conformational entropy. CD spectroscopy studies reveal a small increase in the helical content and a decrease in ?-structure as well as random coil in both proteins. Acrylamide quenching experiments display reduced accessibility of tyrosines, while intrinsic fluorescence spectra show lower tyrosine emission. Furthermore, thermal unfolding experiments, studied by far...
Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical with a variety of biological activities. The ongoing research and clinical trials have proved that this natural phenolic compound has great and diverse pharmacological potencies. Beside its effective antioxidant, antiinflammatory, and antimicrobial/antiviral properties, curcumin is also considered as a cancer chemopreventive agent. While the antioxidant activity of curcumin is well documented, its interaction with DNA and RNA is not fully investigated. This study was designed to examine the interactions of curcumin with calf thymus DNA and yeast RNA in aqueous solution at physiological conditions, using constant DNA and RNA concentration (6.25?mM) and various curcumin/polynucleotide (phosphate...
/sup 125/I-Calmodulin is internalized by isolated rat renal brush border membrane vesicles (BBV) in a time, temperature and calcium dependent manner. Internalization of /sup 125/I-calmodulin into the osmotically sensitive space of BBV was distinguished from binding of the ligand to the outer BBV surface by examining the interaction of ligand and BBV at different medium osmolarities (300-1100 mosm), uptake was inversely proportional to medium osmolarity. Internalized /sup 125/I-calmodulin was intact and Western blots of solubilized BBV with /sup 125/I-calmodulin demonstrated the presence of several calmodulin-binding proteins of 143, 118, 50, 47.5, 46.5 and 35 kilodaltons which could represent potential intravesicular binding sites for the ligand. Heparin and the related glycosaminoglycan heparin sulfate both showed a dose-dependent inhibition (0.5-50 ..mu..g/ml) of /sup 125/I-calmodulin uptake by BBV, ...
The binding of iodine-labelled plasminogen to Helicobacter pylori CCUG 17874 was characterized. Inhibition of the binding was observed after preincubation of H. pylori...Full Text Available
To investigate mechanisms responsible for positive and negative transcriptional control, the authors have utilized two types of promoters that are diffferentially regulated by thyroid hormone (T{sub 3}) receptors. Promoters containing the palindromic T{sub 3} response element TCAGGTCA TGACCTGA are positively regulated by the T{sub 3} receptor after the administration of T{sub 3}, whereas otherwise identical promoters containing the estrogen response element TCAGGTCA CTG TGACCTGA can be regulated negatively; converse effects are observed with the estrogen receptor. They describe evidence that the transcriptional inhibitory effects of the T{sub 3} or estrogen receptors on the estrogen or T{sub 3} response elements, respectively, are imposed by amino acid sequences in the C'-terminal region that colocalize with dimerization and hormone-binding domains and that these sequences can transfer inhibitory functions to other classes of transcription factors. Removal ...
Interleukin 2 (IL-2) is a T-cell-derived lymphokine critical in the activation and proliferation of T cells, B cells, and lymphokine-activated killer cells. It is a glycoprotein of #approx#15,500 daltons that is synthesized and secreted after activation by antigen or mitogen. By using the analogs 8-azidoadensoine 5'-[#gamma#-"3"2P]triphosphate ([#gamma#-"3"2P]8N_3ATP) and nicotinamide 2-azidoadenine [adenylate-"3"2P]dinucleotide ([#alpha#-"3"2P]2N_3NAD"+) as photoaffinity probes, the authors have detected specific, metal ion-requiring nucleotide binding sites on recombinant human IL-2 (rhIL-2). The specificity of these nucleotide interactions with rhIL-2 was demonstrated by saturation effects and by competition by the parent nucleotides at physiologically relevant concentrations. Saturation of photoinsertion into rhIL-2 occurred at 50 #mu#M [#gamma#-"3"2P]8N_3ATP. Saturation of photoinsertion with [#alpha#-"3"2P]2N_3NAD"+ was observed at 180 ...
A major regulatory element required for expression of the human [alpha]-globin genes is located 40 kb upstream of the embryonic [zeta]-globin gene. To understand how this and other locus control region (LCR) elements contribute to high-level expression in erythroid cells, we have performed high-resolution, in vivo dimethyl sulfate footprinting. In addition, we have modified the dimethyl sulfate-based ligation-mediated polymerase chain reaction in vivo footprinting procedure to permit the assessment of interactions at guanine and adenine residues, rather than guanines alone. In vivo footprinting of the human [alpha]-LCR element carried on chromosome 16 in a mouse erythroleukemia cell environment revealed protein occupancy at GATA-1, AP-1/NF-E2, and CACC/GGTGG motifs, specific differences compared with in vitro protein binding, and distinct changes in one region upon dimethyl sulfoxide-induced cellular maturation. No protein contacts were ...
This study sought to quantitate lidocaine's interaction with alpha-1-acid glycoprotein (AAG), human serum albumin (HSA), and AAG in the presence of HSA, and to determine the extent of displacement of lidocaine from its binding site(s) by selected cardiovascular drugs (dipyridamole, disopyramide and quinidine). Since the limited experimental work reported in this area has involved the use of a single lidocaine concentration, this study involved the evaluation of a range of lidocaine concentrations. Lidocaine interaction with plasma proteins (AAG and HSA) was studied at 37/sup 0/C using an isothermal equilibrium dialysis system and /sup 14/C-lidocaine HCl. A dialysis membrane (M.W. cutoff 12,000 to 14,000) separated the two chambers of each dialysis cell. The extent of /sup 14/C-lidocaine dialysis was studied with respect to both drug and protein concentrations. Aliquots of each chamber of each of the cells were ...
Constitutive activation of the oncogenic transcription factor STAT3 frequently occurs in various human malignancies. STAT3 activation involves dimerization via intermolecular pTyr-SH2 interaction. Thus, antagonizing this interaction is a feasible approach to inhibit STAT3 activation for cancer therapy. In order to identify selective STAT3 inhibitors, we developed a biochemical HTS system based on AlphaScreen technology, which measures the abilities of test compounds to antagonize pTyr-SH2 interactions. We screened our chemical libraries using this system and identified 5,15-diphenylporphyrin (5,15-DPP) as a selective STAT3-SH2 antagonist. Selective inhibition of STAT3 nuclear translocation and DNA biding activity was observed in cells treated with 5,15-DPP. IL-6-dependent dimerization of STAT3, c-myc promoter binding and c-myc protein expression were all suppressed by 5,15-DPP, whereas no decrement in ...
X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM) have been conducted on a new fuel cell electrocatalytic material based on a highly porous carbonized polyacrylonitrile (PAN) microcellular foam with very low platinum loading ({approximately}13 to 23 {micro}g/cm{sup 2}). TEM images of this material clearly show the existence of nanometer size platinum particles which are homogeneously distributed in the highly porous carbonized PAN matrix. An XPS study of Pt-loaded PAN indicates that C 1s, O 1s, and N 1s peaks shift to lower binding energies, compared to virgin PAN. It was concluded that special metal-support interaction exists, through the formation of a charge-transfer complex between platinum and pyridine-type nitrogen atoms of PAN support. This interaction leads to the enhancement of the catalytic activity, and the improvement of the long-time stability of this electrocatalyst.
The nuclear pore complexes (NPCs) reversibly disassemble and reassemble during mitosis. Disassembly of the NPC is accompanied by phosphorylation of many nucleoporins although the function of this is not clear. It was previously shown that in the transmembrane nucleoporin gp210 a single serine residue at position 1880 is specifically phosphorylated during mitosis. Using amino acid substitution combined with live cell imaging, time-lapse microscopy and FRAP, we investigated the role of serine 1880 in binding of gp210 to the NPC in vivo. An alanine substitution mutant (S1880A) was significantly more dynamic at the NPC compared to the wild-type protein, suggesting that serine 1880 is important for binding of gp210 to the NPC. Moreover a glutamate substitution (S1880E) closely mimicking phosphorylated serine specifically interfered with incorporation of gp210 into the NPC and compromised its post-mitotic recruitment to the nuclear envelope of ...
We present a fully relativistic formalism for describing neutrino-induced $\\Delta$-mediated single-pion production from nuclei. We assess the ambiguities stemming from the $\\Delta$ interactions. Variations in the cross sections of over 10% are observed, depending on whether or not magnetic-dipole dominance is assumed to extract the vector form factors. These uncertainties have a direct impact on the accuracy with which the axial-vector form factors can be extracted. Different predictions for $C_5^A(Q^2)$ induce up to 40-50% effects on the $\\Delta$-production cross sections. To describe the nucleus, we turn to a relativistic plane-wave impulse approximation (RPWIA) using realistic bound-state wave functions derived in the Hartree approximation to the $\\sigma$-$\\omega$ Walecka model. For neutrino energies larger than 1 GeV, we show that a relativistic Fermi-gas model with appropriate binding-energy correction produces comparable results as ...
The generalized hybrid derivative coupling model has been applied to explore various ground state properties of different nuclei. In this work we have confined our calculation only to the model characterized by the hybridization parameter {alpha} = 1/4 which gives better results than the other models of the same class, as we have seen earlier, for nuclear matter calculations. The binding energy, single-particle energy spectra, density and charge radii of different doubly closed nuclei like {sup 16}O, {sup 40}Ca, {sup 48}Ca, {sup 90}Zr, {sup 132}Sn, {sup 208}Pb have been studied. The success of this model, in describing the doubly closed nuclei, motivates us to extend this calculation further in the case of open shell nuclei after incorporating the pairing interaction and using a BCS transformation. We have calculated the binding energy for such nuclei. We have also studied the isotopic shift for different Pb isotopes with ...
Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the distal C terminus of DAT and colocalized with DAT in dopaminergic neurons. CaMKIIalpha stimulated dopamine efflux via DAT in response to amphetamine in heterologous cells and in dopaminergic neurons. CaMKIIalpha phosphorylated serines in the distal N terminus of DAT in vitro, and mutation of these serines eliminated the stimulatory effects of CaMKIIalpha. A mutation of the DAT C terminus impairing CaMKIIalpha binding also impaired amphetamine-induced dopamine efflux. An in vivo role for CaMKII was supported by chronoamperometry measurements showing reduced amphetamine-induced dopamine efflux in response to the CaMKII inhibitor KN93. Our data suggest that CaMKIIalpha ...
The authors have previously identified a small-cell lung cancer cell line (NCI-H209) that expresses an aberrant, underphosphorylated form of the retinoblastoma protein RB1. Molecular analysis of RB1 mRNA from this cell line revealed a single point mutation within exon 21 that resulted in a nonconservative amino acid substitution (cysteine to phenylalanine) at codon 706. Stable expression of this mutant RB1 cDNA in a human cell line lacking endogenous RB1 demonstrated that this amino acid change was sufficient to inhibit phosphorylation. In addition, this cysteine-to-phenylalanine substitution also resulted in loss of RB1 binding to the simian virus 40 large tumor and adenovirus E1A transforming proteins. These results confirm the importance of exon 21 coding sequences and suggest that the cysteine residue at codon 706 may play a role in achieving a specific protein conformation essential for protein-protein interactions.
Development of selective serotonin transporter (SERT) tracers for single-photon emission tomography (SPET) is important for studying the underlying pharmacology and interaction of specific serotonin reuptake site inhibitors, commonly used antidepressants, at the SERT sites in the human brain. In search of a new tracer for imaging SERT, IDAM (5-iodo-2-[[2-2-[(dimethylamino)methyl]phenyl]thio]benzyl alcohol) was developed. In vitro characterization of IDAM was carried out with binding studies in cell lines and rat tissue homogenates. In vivo binding of [[sup 125]I]IDAM was evaluated in rats by comparing the uptakes in different brain regions through tissue dissections and ex vivo autoradiography. In vitro binding study showed that IDAM displayed an excellent affinity to SERT sites (K[sub i]=0.097 nM, using membrane preparations of LLC-PK[sub 1] cells expressing the specific transporter) and showed more ...
Eukaryotic genomes encode a zinc finger protein (ZPR1) with tandem ZPR1 domains. In response to growth stimuli, ZPR1 assembles into complexes with eukaryotic translation elongation factor 1A (eEF1A) and the survival motor neurons protein. To gain insight into the structural mechanisms underlying the essential function of ZPR1 in diverse organisms, we determined the crystal structure of a ZPR1 domain tandem and characterized the interaction with eEF1A. The ZPR1 domain consists of an elongation initiation factor 2-like zinc finger and a double-stranded {beta} helix with a helical hairpin insertion. ZPR1 binds preferentially to GDP-bound eEF1A but does not directly influence the kinetics of nucleotide exchange or GTP hydrolysis. However, ZPR1 efficiently displaces the exchange factor eEF1B from preformed nucleotide-free complexes, suggesting that it may function as a negative regulator of eEF1A activation. Structure-based mutational and ...
In virtually all forms of life on earth, proteins in each cell are made according to a genetic blueprint, in the form of DNA. The translation of copies of this genetic blueprint (in the form of messenger RNA) into polypeptides is performed on the ribosome, a highly complex molecular machine composed of RNAs and proteins. To this end, special adaptor molecules called transfer RNAs are lined up by the ribosome in the sequence dictated by the genetic code, such that the amino acids carried by these molecules can be linked into a polypeptide. Several cofactors are involved in these processes, some of which require energy freed up by GTP hydrolysis. Although the ribosome was discovered more than 50 years ago, its structure has only been solved recently by X-ray crystallography. Another technique, cryo-electron microscopy, is starting to contribute toward our understanding of the ribosome's function, by portraying its conformational changes and binding ...
Recently, molecular clusters are the subject of several experimental and computational studies by means of their bonding structures. We studied, first time, small difluorine monoxide clusters such as dimer (linear, cyclic, bifurcated), trimer and tetramer structures using B3LYP variant of density functional theory with cc-pVDZ basis set. On the basis of the optimized geometry, various energy properties such as binding energy, molecular orbital energies, two and three body interaction energies have been calculated. Additionally dipole moment, polarizability, anisotropic polarizability and hyper polarizability have been calculated and compared with monomer structure.
We previously reported that puromycin-insensitive leucyl-specific aminopeptidase (PILSAP) is required for vascular endothelial growth factor (VEGF)- and basic fibroblast growth factor (bFGF)-induced angiogenesis and for endothelial differentiation from embryonic stem (ES) cells via the aminopeptidase activity of PILSAP. In this study, we searched for molecules that function during angiogenesis with PILSAP. We performed proteome analysis of nuclear extracts from embryoid bodies (EBs) made from ES cells transfected with mutant PILSAP lacking aminopeptidase activity and mock EBs. We identified pigpen, a 67-kDa nuclear coiled body component protein. Immunoprecipitation and western blotting demonstrated the binding of PILSAP and pigpen in endothelial cells (ECs), and this interaction was enhanc...
When operating a nuclear power plant the necessity arise to eliminate various defects of building constructions, to seal joints and transitional elements. The authors present data concerning the production of a sealing composition made of epoxy resin and used for NPP premises of emergency location. Analytical relations are presented between the properties of the composition (adhesion strength, water absorption and others) and its structure. Physical, mechanical and thermal properties and structural peculiarities are determined in the process of interaction between the filling and binding agents. The composition sustains sealing properties under environmental conditions at he presence of an air - vapour mixture with 160 degrees C"o temperature and 0.3 MPa surplus pressure. (author).
Antibodies to hemoglobin have been studied with a radioimmunoassay which employs ["1"4C]carbamylated (= carbamoylated) hemoglobin S. An antiserum raised against hemoglobin S, which initially discriminated poorly between hemoglobins S and A, was fractionated by absorption to a column of Sepharose to which a synthetic peptide corresponding to the first 13 amino-acid residues of the #beta# chain of sickle hemoglobin had been covalently bound. A subpopulation of the antiserum was eluted from this column with 4 M guanidine . HCl. These antibodies showed binding to hemoglobin S but not to hemoglobin A and this interaction could be inhibited by the synthetic peptide. These antibodies, of demonstrated fine structural specificity, may be useful in the detection of sickle hemoglobin and in the study of its structure in solution.
Background: Thyroid-stimulating autoantibodies (TSAb) bind to the thyrotropin receptor (TSHR) extracellular domain, or ectodomain (ECD), comprising a leucine-rich repeat domain (LRD) linked by a hinge region to the transmembrane domain (TMD). The LRD (residues 22???260; signal peptide 1???21) contains two disulfide-bonded loops at its N-terminus. In the crystal structure of the isolated LRD complexed with human TSAb monoclonal antibody (mAb) M22, N-terminal disulfide loop 1 (residues 22???30) could not be determined because of crystal disorder. Nevertheless, present crystal structure data are interpreted to exclude a role for the LRD N-terminal disulfide loops in the TSAb epitope(s), contradicting prior functional evidence of a role for these loops in TSAb function. Materials and Methods: ...
In situ assembly states of rat adipocyte glucose transport protein in plasma membrane (PM) and in microsomal pool (MM) were assessed by measuring target size (TS) of D glucose-sensitive, cytochalasin B binding activity. High energy radiation inactivated the binding in both PM and MM by reducing the total capacity of the binding (B/sub T/) without affecting the dissociation constant (K/sub D/). The reduction in B/sub T/ as a function of radiation dose was analyzed based on classical target theory, from which TS was calculated. TS in the PM of insulin-treated adipocytes was 58 KDa. TS in the MM of noninsulin-treated and insulin-treated adipocytes were 112 and 109 KDa, respectively. With MM, however, inactivation data showed anomalously low radiation sensitivities at low radiation doses showing a shoulder in the semilog plots, which may be due to an interaction with a radiation sensitive inhibitor. With ...
A single amino acid substitution (Asp #-># Asn) at position 138 of E. coli EF-Tu was induced in the tufA gene by an M13 phage oligonucleotide site-directed mutagenesis protocol. The mutated tufA gene was then subcloned in a plasmid vector and expressed in maxicells. The properties of ["3"5S]methionine labelled mutant and wild type EF-Tu's were compared by in vitro assays. Mutant and wild-type EF-Tu's bound EF-Ts with approximately equal affinities. The 138-Asn mutation greatly reduced the protein's affinity for GDP; however, this mutation dramatically increased the proteins affinity for XDP. The mutant protein forms a stable complex with phe-tRNA and XTP, which binds to ribosomes; whereas, it does not form a complex with phe-tRNA and GTP. These results suggest that in EF-Tu x NDP complexes amino acid residue 138 must interact with the substituent on C-2 of the purine ring. Thus in wild-type EF-Tu Asp-138 would H-bond to 2-NH_2 of GDP, and in ...
The interaction of the globular protein lysozyme with silica nanoparticles of diameter 20 nm was studied in a pH range between the isoelectric points (IEPs) of silica and the protein (pH 3-11). The adsorption affinity and capacity of lysozyme on the silica particles is increasing progressively with pH, and the adsorbed protein induces bridging aggregation of the silica particles. Structural properties of the aggregates were studied as a function of pH at a fixed protein-to-silica concentration ratio which corresponds to a surface concentration of protein well below a complete monolayer in the complete-binding regime at pH > 6. Sedimentation studies indicate the presence of compact aggregates at pH 4-6 and a loose flocculated network at pH 7-9, followed by a sharp decrease of aggregate size near the IEP of lysozyme. The structure of the bridged silica aggregates was studied by cryo-transmission electron microscopy (cryo-TEM) and small-angle ...
Nuclear testing at and around the Nevada Test Site (NTS) resulted in widespread contamination from transuranic and other radionuclides, as well as from other toxic inorganic and organic contaminants. The type of contamination, including spatial distribution and type of radionuclides present, depends on the type of testing performed. Remediation of the contaminated areas is currently under way. The optimum in situ or ex situ remediation technology depends on the degree of interaction between the particular radionuclide, or contaminant in general, and the soil matrix, among other factors. The objective of this project was to evaluate the sorption affinity of NTS soils for common non-transuranic radionuclides. The sorption of cobalt (Co) on soils from two different areas of the NTS, namely the Little Feller and Cabriolet event sites, was studied. Experiments were conducted as a function of pH, solid concentration, total Co concentration, ionic strength, and particle ...
When preadipocytes differentiate into adipocytes, several differentiation-linked genes are activated. Lipo-protein lipase (LPL) is one of the first genes induced during this process. To investigate early events in adipocyte development, we have focused on the transcriptional activation of the LPL gene. For this purpose, we have cloned and fused different parts of intragenic and flanking sequences with a chloramphenicol acetyltransferase reporter gene. Transient transfection experiments and DNase I hypersensitivity assays indicate that several positive as well as negative elements contribute to transcriptional regulation of the LPL gene. When reporter gene constructs were stably introduced into preadipocytes, we were able to monitor and compare the activation patterns of different promoter deletion mutants at selected time points representing the process of adipocyte development. We could delimit two cis-regulatory elements important for gradual activation of the LPL gene during ...
HMGA2 is a DNA minor-groove binding protein. We previously demonstrated that HMGA2 binds to AT-rich DNA with very high binding affinity where the binding of HMGA2 to poly(dA-dT)2 is enthalpy-driven...Full Text Available
Receptor interacting protein 140 (RIP140) is a coregulator for numerous nuclear receptors and transcription factors and primarily exerts gene-repressive activities on various target genes. We previously identified a spectrum of posttranslational modifications on RIP140 that augment its property and biological activity. In T(3)-triggered biphasic regulation of cellular retinoic acid binding protein 1 (Crabp1) gene along the course of fibroblast-adipocyte differentiation, we found TRAP220(MED1) critical for T(3)-activated chromatin remodeling whereas RIP140 essential for T(3)-repressive chromatin remodeling of this gene promoter. In this current study, we aim to examine whether and how RIP140 replaces TRAP220(MED1) on the CrabpI promoter in differentiating adipocyte cultures. We find increasing recruitment of RIP140 to this promoter, with corresponding reduction in TRAP220(MED1) recruitment during the T(3)-repressive phase. We also uncover direct ...
In vitro the binding of polyribosomes to smooth endoplasmic-reticulum membranes is more sensitive to ionic strength than is the binding to rough endoplasmic-reticulum membranes. Polyribosomes...Full Text Available
The levels of in vitro protein binding of cefonicid and cefuroxime in human adult and neonatal sera were compared. Binding parameters for each drug were determined within the concentration range of...Full Text Available
Parasitic nematodes cause serious diseases in humans, animals, and plants. They have limited lipid metabolism and are reliant on lipid-binding proteins to acquire these metabolites from their hosts....Full Text Available
The drug-binding properties of human alpha-foetoprotein (alpha FP) were investigated by a fluorescence-spectral method. Human alpha FP was shown to bind to albumin's site I marker (warfarin, phenylbutazone),...Full Text Available
The sequences of the peptide binding domains of 33 70 kd heat shock proteins (hsp70) have been aligned and a consensus secondary structure has been deduced. Individual members showed no significant...Full Text Available
Drosophila melanogaster has long been at the forefront of studies of transcriptional regulation in animals. Many fundamental ideas--such as cis control elements that act over long distances, the regulation of development by hierarchical cascades of transcription factors, dosage compensation, and position effect variegation--originated from studies of the fruit fly. The recent completion of the euchromatic DNA sequence of Drosophila is another breakthrough. The sequence data highlight important unanswered questions. For example, only one-fifth of the 124 Mb of Drosophila euchromatic DNA codes for protein. The function of the remaining 100 Mb of mostly unique DNA is largely unknown. Some proportion of this non-reading frame DNA must encode the functional recognition sites targeted by the approximately 700 sequence-specific DNA binding proteins that regulate transcription in Drosophila, but what proportion? Most or very little? Promoter sequences by definition contain ...
The photophysical investigation of different para-substituted tetraphenylporphyrins (TP), viz., meso-tetra(4'-hydroxyphenyl)-21H-23H-porphyrin(1),meso-tetrakis (4'-hex-5-enyloxyphenyl)-21H-23H-porphyrin(2), meso-tetrakis(4'-oct-7-enyloxyphenyl)-21H-23H-porphyrin(3) and meso-tetrakis(4'-undecyloxyphenyl)-21H-23H-porphyrin (4) revealed that except for quantum yield (#phi#) the para-substitution has little effect on any other photophysical properties like lifetime, excitation, emission wavelength, etc. The host-guest type interactions of these tetraarylporphyrins (TP 1-4), with [60]-fullerene (F) have been studied with "1H NMR and fluorescence spectrometric techniques in carbon tetrachloride medium. Fluorescence studies revealed that the Q band of the TPs was sufficiently quenched upon addition of F. All the fullerene/porphyrin systems were found to produce stable complexes with 1:1 stoichiometry. Binding constants (K) of all the ...
1. Choline, and the choline analogues monoethylcholine (MEC) and N-aminodeanol (NAD) were examined for prophylactic activity in acute acetylcholinesterase inhibitor toxicity in mice. The rank order of potency of the compounds was MEC greater than NAD greater than choline. 2. Simultaneous administration of MEC (60 mg kg-1) or NAD (200 mg kg-1) with physostigmine reduced lethality to 17 and 13% respectively. MEC (60 mg kg-1) completely protected against disopropylfluorophosphate (DFP) and diazinon toxicity, and NAD reduced lethality to 17% for both agents. Choline (200 mg kg-1) exhibited only negligible antidotal activity against the inhibitors. 3. In vitro concentrations of choline, MEC, and NAD, similar to the estimated concentration obtained in vivo in the acute toxicity study, produced mixed inhibition of mouse brain acetylcholinesterase. The inhibition was dose-related and was additive to the inhibition produced by the cholinesterase inhibitors. 4. All three analogues reduced ligand ...
Laron syndrome (LS) is an autosomal recessively inherited condition characterized by insensitivity to endogenous and exogenous GH. Affected individuals have severe episodes and other characteristic features. GH receptor gene mutations are present in all affected individuals in whom molecular studies have been reported. The GH receptor is a plasma membrane-spanning protein in which the extracellular domain binds circulating GH and the intracellular domain interacts with the JAK-2 kinase and possibly other intracellular signaling molecules. GH receptor dimerization occurs on GH binding and is thought to be required for normal signal transduction. We have studied the GH receptor genes of four unrelated individuals affected with LS from the United States, Italy, Saudi Arabia, and India. We have identified four different missense mutations that alter consecutive amino acids 152 to 155 in or near the dimerization domain of the GH ...
An essential issue in gallium (Ga)-stabilized fcc-phase plutonium ({delta}-Pu) is the formation of helium (He) voids and bubbles emanating from the radiolytic decay of the Pu. The rate of formation of He voids and bubbles is related to the He-defect formation energies and their associated migration barriers. The size and shape distributions of the bubbles are coupled to these critical migration processes. The values of the defect formation energies, internal pressure, and migration barriers can be estimated from atomistic calculations. Complicating this picture is the destruction of He-filled voids and bubbles by subsequent radiolytic decay events. The present study concerns the construction of the necessary potential energy surfaces for the Pu-He and He-He interactions within the modified embedded atom method (MEAM). Once fully tested, the potentials will be used to estimate the He-defect formation energies and barriers to the migration of these defects for both ...
Several series of pyrimidine nucleosides were evaluated as part of a larger program to develop non-invasive brain imaging agents. The interaction of these antitumor/antiviral nucleosides with an NBMPR-sensitive murine erythroctye nucleoside transporter was evaluated by determining their inhibitory effect (K_i) on zero-trans influx of thymidine. Within each series of compounds, which had F, Cl, Br or I as halogen substituents, an increase in size of the halogen atom or a decrease in electronegativity decreased affinity for the transporter. Partition coefficients (P) of these pyrimidine nucleosides were measured to determine their potential to diffuse across the blood-brain-barrier (BBB). Most of the pyrimidine nucleosides had lower P values (log P < 0.9), and were considered to be poor candidates for simple diffusion across the BBB, although an active BBB transport mechanism for some nucleosides could be operative. For a given series, it was found that log P ...
Neuron-restrictive silencer factor (NRSF) binds its consensus element to repress the transcription of various genes. The dominant-negative form (dnNRSF) has a hypertrophic effect on cardiogenesis through an unidentified mechanism. We examined the involvement of transient receptor potential (TRP) channel proteins, using transgenic mice overexpressing dnNRSF (dnNRSF mice). Electrophoretic mobility-shift assays revealed an interaction between NRSF and a neuron-restrictive silencer element-like sequence in intron 4 of TRPC1 genomic DNA. According to RT-PCR and Western analyses, TRPC1 was up-regulated in dnNRSF mouse heart. Transient overexpression of TRPC1 in HEK 293T cells increased the activity of the nuclear factor in activated T cells (NFAT) promoter and stimulated store-operated Ca"2"+ channel (SOCC)-mediated Ca"2"+ entry. Transfection of TRPC1 into primary cardiomyocytes increased NFAT activity, indicating a major role for TRPC1 in NFAT ...
Natural gas is essential to the world economy. Gas now accounts for almost a quarter of OECD primary energy requirements and is expected to become the second most important fuel in the world in the next decade. Industrial and residential consumers increasingly rely on natural gas to keep their houses warm, their lights on and their factories running. Meanwhile the gas industry itself has entered a new phase. Where gas used to be restricted to regional markets, it is now increasingly traded on a global scale. While gas production and transport requires long-term investment, now it is optimised on a short-term basis. Demand continues to grow, but local gas production has become much more expensive. How should we react? How will demand be satisfied? What changes are required to promote flexibility and trade? What are the implications for gas security, investment and interdependence? At stake is an opportunity to diversify supply and demand - but this goal is threatened by barriers to ...
The massive stars in the Galactic center inner arcsecond share analogous properties with the so-called Hot Jupiters. Most of these young stars have highly eccentric orbits, and were probably not formed in-situ. It has been proposed that these stars acquired their current orbits from the tidal disruption of compact massive binaries scattered toward the proximity of the central supermassive black hole. Assuming a binary star formed in a thin gaseous disk beyond 0.1 pc from the central object, we investigate the relevance of disk-satellite interactions to harden the binding energy of the binary, and to drive its inward migration. A massive, equal-mass binary star is found to become more tightly wound as it migrates inwards toward the central black hole. The migration timescale is very similar to that of a single-star satellite of the same mass. The binary's hardening is caused by the formation of spiral tails lagging the stars inside the binary's ...
Group B Streptococcus (GBS) is the leading cause of meningitis in newborn infants. Bacterial cell surface appendages, known as pili, have been recently described in streptococcal pathogens, including GBS. The pilus tip adhesin, PilA, contributes to GBS adherence to blood-brain barrier (BBB) endothelium; however, the host receptor and the contribution of PilA in central nervous system (CNS) disease pathogenesis are unknown. Here we show that PilA binds collagen, which promotes GBS interaction with the ?(2)?(1) integrin resulting in activation of host chemokine expression and neutrophil recruitment during infection. Mice infected with the PilA-deficient mutant exhibit delayed mortality, a decrease in neutrophil infiltration and bacterial CNS dissemination. We find that PilA-mediated virulence is dependent on neutrophil influx as neutrophil depletion results in a decrease in BBB permeability and GBS-BBB penetration. Our results suggest that the ...
1. The fluorescent fatty acid probe 11-(dansylamino)undecanoic acid (DAUDA) binds with high affinity to bovine and human serum albumin (BSA and HSA) at three sites. 2. The Kd of the primary binding...Full Text Available
We describe a method for affinity purification of sequence-specific DNA binding proteins that is fast and effective. Complementary chemically synthesized oligodeoxynucleotides that contain a recognition site for a sequence-specific DNA binding protein are annealed and ligated to give oligomers. This DNA is then covalently coupled to Sepharose CL-2B with cyanogen bromide to yield the affinity resin. A partially purified protein fraction is combined with competitor DNA and subsequently passed through the DNA-Sepharose resin. The desired sequence-specific DNA binding protein is purified because it preferentially binds to the recognition sites in the affinity resin rather than to the nonspecific competitor DNA in solution. For example, a protein fraction that is enriched for transcription factor Sp1 can be further purified 500- to 1000-fold by two sequential affinity chromatography steps to give Sp1 of an ...
BackgroundDespite an ever-improving understanding of the molecular biology of cancer, the treatment of most cancers has not changed dramatically in the past three decades and drugs that do not discriminate between tumor cells and normal tissues remain the mainstays of anticancer therapy. Since Hsp90 is typically involved in cell proliferation and survival, this is thought to play a key role in cancer, and Hsp90 has attracted considerable interest in recent years as a potential therapeutic target.MethodsWe focused on the interaction of Hsp90 with its cofactor protein p60/Hop, and engineered a cell-permeable peptidomimetic, termed "hybrid Antp-TPR peptide", modeled on the binding interface between the molecular chaperone Hsp90 and the TPR2A domain of Hop.ResultsIt was demonstrated that this designed hybrid Antp-TPR peptide inhibited the interaction of Hsp90 with the TPR2A domain, inducing cell death of breast, pancreatic, ...
In order to understand the role of EGF in the development of human mammary epithelial tissue, we analysed the binding of /sup 125/I-EGF to sections of breast cancer biopsies. A mean specific /sup 125/I-EGF binding of 8.9 fmol per mg protein was estimated in thin sections of 17 breast cancer biopsies. Microautoradiographic analysis of /sup 125/I-EGF binding to the tissue sections was applied to demonstrate that EGF was bound predominantly to mammary epithelial cells. The binding was clearly correlated to the number of mitoses of mammary epithelial cells in the same samples. The highest EGF binding and proliferation rates were found in biopsies from breast cancer with axillary lymph-node metastases.
The authors have identified a protein present only in erythroid cells that binds to two adjacent sites within an enhancer region of the chicken {beta}-globin locus. Mutation of the sites, so that binding by the factor can no longer be detected in vitro, leads to a loss of enhancing ability, assayed by transient expression in primary erythrocytes. Binding sites for the erythroid-specific factor (Eryf1) are found within regulatory regions for all chicken globin genes. A strong Eryf1 binding site is also present within the enhancer of at least one human globin gene, and proteins from human erythroid cells (but not HeLa cells) bind to both the chicken and the human sites.
Shewanella oneidensis MR-1 is a model environmental organism that possesses diverse respiratory capacities, including the ability to reduce soluble Cr(VI) to sparingly soluble, less toxic Cr(III). Effective bioremediation of Cr-contaminated sites requires knowledge of the molecular mechanisms and regulation of heavy metal resistance and biotransformation by dissimilatory metal-reducing bacteria. Towards this goal, our ERSP-funded work is focused on the identification and functional analysis of genes/proteins comprising the response pathways for chromate detoxification and/or reduction. Previous transcriptomic profiling and whole-cell proteomic analyses implicated the involvement of a functionally undefined DNA-binding response regulator (SO2426) and a putative azoreductase (SO3585) in the chromate stress response of MR-1. Here we describe a detailed functional analysis of SO2426 and SO3585 in order to begin to understand the role of these proteins in the cellular ...
This poster describes single-molecule tracking and total internal reflection fluorescence microscopy. It discusses whether the carbohydrate-binding module (CBM) moves on cellulose, how the CBM binds to cellulose, and the mechanism of cellulosome assembly.
1. The stereospecificity of the enantiomers of LY253352, a potent and selective alpha 1-adrenoceptor antagonist, were studied in the human prostate and canine brain using radioligand receptor binding...Full Text Available
Peripheral subunit binding domains (PSBDs) are integral parts of large multienzyme complexes involved in carbohydrate metabolism. PSBDs facilitate shuttling of prosthetic groups between different catalytic...Full Text Available
ATP-binding cassette transporters (ABC transporters) utilize the energy of ATP hydrolysis to translocate an unusually diverse set of substrates across cellular membranes. ABCA4, also known as...Full Text Available
The homologous sequences observed for many calcium binding proteins such as parvalbumin, troponin C, the myosin light chains, and calmodulin has lead to the hypothesis that these proteins have homologous...Full Text Available
Serum protein and lipid concentrations as well as the serum protein binding of propranolol, diazepam and phenytoin were measured in normal weight and obese volunteers. Concentrations of alpha 1-acid...Full Text Available
Starting with a #LAMBDA#-nucleus potential, a semi-empirical formula, which gives a fairly satisfactory account of the ground state #LAMBDA#-binding energy of light hypernuclei, if the very light nuclei are ignored has been obtained. (author).
To investigate the role of thyroxine-binding globulin (TBG) and albumin in the availability of thyroid hormones to peripheral tissues, comprehensive kinetic studies of thyroxine (T4) and triiodothyronine...Full Text Available
1. The structural requirements of an allosteric barbiturate binding site on acetylcholine receptor-rich membranes isolated from Torpedo electroplaques have been characterized by the ability of fourteen...Full Text Available
Variant alleles of the mannose binding lectin (MBL) gene are associated with increased susceptibility to infection and polymorphisms of tumour necrosis factor and lymphotoxin alpha genes (TNF, LTA)...Full Text Available
It has been sixty years since the Millers first described the covalent binding of carcinogens to tissue proteins. Protein covalent binding was gradually overshadowed by the emergence of DNA...Full Text Available
The plasma protein binding of phenytoin was investigated in 100 epileptic patients, using equilibrium dialysis at 37 degrees C. The unbound fractions of phenytoin in plasma formed a skewed distribution,...Full Text Available
The purpose of the present work was to study the pharmacokinetics and the protein binding (free fraction of the drug) of ceftriaxone (CTX) during pregnancy. Nine pregnant women (ages, 20 to 34 years)...Full Text Available
The brain’s ability to bind incoming auditory and visual stimuli depends critically on the temporal structure of this information. Specifically, there exists a temporal window of audiovisual...Full Text Available
Cd-binding protein was extracted from tomato roots and purified on QAE-Sephadex A-25 and on Sephadex G-75 in 1 molar KCl buffer. The protein preparation was light brown and contained predominantly Cd...Full Text Available
The Aer protein in Escherichia coli is a membrane-bound, FAD-containing aerotaxis and energy sensor that putatively monitors the redox state of the electron transport system. Binding...Full Text Available
BackgroundThe binding of peptide fragments of antigens to class II MHC is a crucial step in initiating a helper T cell immune response. The identification of such peptide epitopes...Full Text Available
End binding proteins (EBs) are highly conserved core components of microtubule plus-end tracking protein networks. Here we investigated the roles of the three mammalian EBs in controlling microtubule...Full Text Available
The bulky octahedral complex, Rh(bpy)2chrysi3+ (chrysi = 5, 6- chrysenequinone diimine), binds single base mismatches in a DNA duplex with micromolar binding affinities...Full Text Available
The effect of chronic administration of phenobarbital on the binding of phorbol-12,13-dibutyrate (({sup 3}H)PDBu), an activator of protein kinase C (PKC), was examined in rat liver microsomes. A significant increase in the number of binding sites was observed in microsomes of Fisher 344 rats. However, no change appeared in liver cytosol binding of PDBu. Consequently, a translocation process of PKC is unlikely. The increase in ({sup 3}H)PDBu binding in liver microsomes is significant 24 h. after one injection of phenobarbital and reaches its maximum in 2 days. In other strains of rats (ACI and lean Zucker), significant differences were found in the increase of ({sup 3}H)PDBu binding in microsomes. Fisher 344 were the most sensitive, lean Zucker rats, the least sensitive. Those results parallel the pentoxy-resorufin O demethylase activity in the microsomes of the same animals. EC{sub ...
The binding of amphiphilic molecules to lipid bilayers is followed by 19F NMR using chemical shift and line shape differences between the solution and membrane-tethered states of...Full Text Available
It has been postulated that thrombin binds to endothelial cells through, at least in part, cell surface glycosaminoglycans such as heparan sulfate, which could serve as antithrombin cofactor on the...Full Text Available
Ethylene rapidly and transiently up-regulates the activity of several monomeric GTP-binding proteins (monomeric G proteins) in leaves of Arabidopsis as determined by two-dimensional gel electrophoresis...Full Text Available
During antibiotic drug development, media are frequently spiked with either serum/plasma or protein supplements to evaluate the effect of protein binding. Usually, previously reported serum or plasma...Full Text Available
Mutational inactivation of the RB1 tumor suppressor gene initiates retinoblastoma and other human cancers. RB1 protein (pRb) restrains cell proliferation by binding...Full Text Available
1 The plasma protein binding of theophylline was determined after addition of [14C]-theophylline (15 micrograms/ml) to plasma from 24 healthy drug-free volunteers and equilibrium dialysis for 2 h at...Full Text Available
BackgroundSteroidogenic acute regulatory (StAR) protein related lipid transfer (START) domains are small globular modules that form a cavity where lipids and lipid hormones bind....Full Text Available
Cellular cholesterol homeostasis is controlled by sterol-regulated proteolysis of membrane-bound transcription factors called sterol-regulatory element binding proteins (SREBPs). CPP32, a cysteine protease,...Full Text Available
The binding mode of telomestatin to G-quadruplex DNA has been investigated using electrospray mass spectrometry, by detecting the intact complexes formed in ammonium acetate. The mass measurements show...Full Text Available
It is well known that DNA strands bind to silica surfaces in the presence of high concentrations of chaotropic salts. We developed simple methods to evaluate binding and recovery of DNA on flat...Full Text Available
Recombinant biotin-binding phages were affinity-selected from a random peptide library expressed on the surface of filamentous phage. Phage binding to biotinylated proteins was half-maximally inhibited...Full Text Available
Kinetics and thermodynamics of the binding of a fluorescent lipid amphiphile, Rhodamine Green™-tetradecylamide (RG-C14:0), to bovine serum albumin were characterized in an equilibrium...Full Text Available
The Protein Data Bank contains the description of more than 45,000 three-dimensional protein and nucleic-acid structures today. Started to exist as the computer-readable depository of crystallographic...Full Text Available
BackgroundMolecular docking methods are commonly used for predicting binding modes and energies of ligands to proteins. For accurate complex geometry and binding energy estimation,...Full Text Available
BackgroundA relevant problem in drug design is the comparison and recognition of protein binding sites. Binding sites recognition is generally based on geometry often combined with...Full Text Available
Full text: Magnetic multilayer materials are becoming technologically important as they provide a more efficient means of magnetic reading and storage through utilisation of their giant magnetoresistance and oscillatory magnetic coupling. This study presents preliminary tight-binding calculations with a view of developing a consistent tight-binding model of `spin valve` Fe-Cu-Fe tri-layer materials. Further work involves using a self-consistent tight-binding approach to obtain a more accurate picture of this system and a better understanding of surface effects at the Fe-Cu interface 1 fig., 4 refs.
The effect of in vitro and in vivo administration of ethanol on the binding of "3"5S-t-butyl-bicyclophosphorothionate ("3"5S-TBPS) to cortical brain membranes of C57B1 mice was investigated using KCl (100 mM) containing assay media. The in vitro addition of ethanol produced a dose-dependent inhibition of basal "3"5S-TBPS binding. In the presence of chloride ions, GABA and pentobarbital had a biphasic action (stimulation followed by inhibition) on "3"5S-TBPS binding, whereas diazepam only stimulated the binding. Ethanol reduced the stimulatory effects of GABA and pentobarbital in a dose-dependent manner, but had no effect on the enhancement of "3"5S-TBPS binding produced by diazepam. "3"5S-TBPS binding to cortical brain membranes was inhibited by the putative Cl"- channel blocking agent DIDS. This inhibitory action of DIDS was significantly, and dose-dependently ...
In rat adipocyte membranes, both beta-adrenergic agonists and beta-adrenergic antagonists competed with (--)(/sup 3/H)dihydroalprenolol for high affinity (KD 2-4 nM) and low capacity binding sites. The antagonists but not the agonists competed with (--)(/sup 3/H)dihydroalprenolol for lower affinity and higher capacity sites. The present studies were performed in order to characterize the adipocyte beta-adrenergic receptor and distinguish it from low affinity, higher capacity sites which were heat-labile and not stereoselective. When isoproterenol was used to define the nonspecific binding, saturation studies showed a single binding site with a capacity of approximately 100 fmol/mg membrane protein (corresponding to approximately 50,000 sites/adipocyte). Binding was saturated by 10 nM (--)(/sup 3/H)dihydroalprenolol. Approximate KD's of 204 nM were observed. Kinetic analysis of (--)(/sup ...
Human serum albumin (HSA) has two primary binding sites for drug molecules. These sites selectively bind different dansylated amino acid compounds, which—due to their intrinsic fluorescence—have...Full Text Available
Transcription activation of sulfur metabolism in yeast is dependent on two DNA binding factors, the centromere binding factor 1 (Cbf1) and Met4. While the role of Met4 was clearly established by showing...Full Text Available
The glass gene is required for proper photo-receptor differentiation during development of the Drosophila eye glass codes for a DNA-binding protein containing five zinc fingers that we show is a transcriptional activator. A comparison of the sequences of the glass genes from two species of Drosophila and a detailed functional domain analysis of the Drosophila melanogaster glass gene reveal that both the DNA-binding domain and the transcriptional-activation domain are highly conserved between the two species. Analysis of the DNA-binding domain of glass indicates that the three carboxyl-terminal zinc fingers alone are necessary and sufficient for DNA binding. We also show that a deletion mutant of glass containing only the DNA-binding domain can behave in a dominant-negative manner both in vivo and in a cell culture assay that measures transcriptional activation. PMID:7604032
Studies of various established human bladder and renal carcinoma cell lines cultured in vitro demonstrated the presence of specific, saturable, high affinity binding sites for /sup 125/I-labeled human interferon Beta ser IFN-beta ser). This recombinant produced interferon labeled with approximately one atom of /sup 125/I/molecule of IFN expressed minimal or no loss of antiviral activity. A single class of binding sites (1000-2000/cell) with an affinity constant of 10(10)-10(11) L/M was measured at 4 degrees C for cells exhibiting widely different sensitivity to the antiproliferative effect of IFN-beta ser. Major fluctuations in the binding of /sup 125/I-labeled IFN-beta ser to cellular receptors were observed during in vitro proliferation of four of five cell lines examined. A significant decrease (P less than 0.001) in specific binding was observed 48 h after cultures were established. Cell cycle ...
Derivatives of angiotensin with a sarcosine substitution at the carboxy terminus and an aliphatic amino acid substitution at the amino terminus have been shown to be competitive ligands for the angiotensin receptor. Scatchard plots derived from saturation isotherm data in bovine adrenal particulates consistently demonstrate three to five times the number of binding sites for "1"2"5I-Sarl,Ile8-AII ("1"2"5I-SI-AII) than for "1"2"5I-AII in experiments in which the two ligands are run side-by-side. A significant difference between "1"2"5I-AII and "1"2"5I-SI-AII binding to detergent solubilized angiotensin receptors was observed. Of the "1"2"5I-AII binding sites, about 85-90% were recovered upon solubilization. In contrast, the recovery of "1"2"5I-SI-AII binding sites was only 4-5%. To determine whether binding sites labeled in the soluble state represent biologically significant AII ...
TC inhibits protein synthesis in E. coli by interfering with aminoacyl-tRNA binding to the ribosomal A site, and there is strong evidence that such inhibition results from TC binding to a high affinity site on the 30S subunit. The SPORE approach has been used to define those 30S proteins that are potentially important for high affinity TC binding, measured as the (/sup 3/H)-TC co-sedimenting with the reconstitution particle through a sucrose density gradient. Reverse phase-HPLC has been used both to prepare ribosomal proteins and to analyze the protein content of reconstituted particles. The results obtained so far show that protein S7, as well as some proteins linked to S7 in the 30S assembly map, are important for TC binding, whereas other ribosomal proteins are not. These results are in very good accord with their earlier photoaffinity labeling studies that strongly implicated S7 as forming part of ...
Abstract TLR9 recognizes unmethylated CpG-containing DNA commonly found in bacteria. Synthetic oligonucleotides containing CpG-motifs (CpG ODNs) recapitulate the activation of TLR9 by microbial DNA, whereas inversion of the CG dinucleotide within the CpG motif to GC (GpC ODNs) renders such ODNs inactive. This difference cannot be attributed to binding of ODNs to the full-length TLR9 ectodomain, as both CpG and GpC ODNs bind comparably. Activation of murine TLR9 requires cleavage into an active C-terminal fragment, which binds CpG robustly. We therefore compared the ability of CpG and GpC ODNs to bind to full-length and C-terminal TLR9, and their impact on the cleavage of TLR9. We found that CpG binds better to C-terminal TLR9 when compared with GpC, despite comparably low binding of both O...
Herpes simplex virus type-1 (HSV-1) entry into target cell is initiated by the ionic interactions between positively charged viral envelop glycoproteins and a negatively charged cell surface heparan sulfate (HS). This first step involves the induction of HS-rich filopodia-like structures on the cell surface that facilitate viral transport during cell entry. Targeting this initial first step in HSV-1 pathogenesis, we generated different zinc oxide (ZnO) micro-nano structures (MNSs) that were capped with multiple nanoscopic spikes mimicking cell induced filopodia. These MNSs were predicted to target the virus to compete for its binding to cellular HS through their partially negatively charged oxygen vacancies on their nanoscopic spikes, to affect viral entry and subsequent spread. Our results demonstrate that the partially negatively charged ZnO-MNSs efficiently trap the virions via a novel virostatic mechanism rendering them unable to enter into ...
Vascular endothelial growth factor (VEGF) is a mitogen that is critically involved in vasculogenesis, angiogenesis, and hematopoiesis. However, what and how transcription factors participate in the regulation of vegf gene expression are not fully understood. Here we report the cloning and sequencing of the zebrafish vegf promoter which revealed that the promoter contains a number of bone morphogenetic protein (BMP)-activated Smad binding elements (SBE), implicating Smad1 and Smad5 in the regulation of BMP-induced expression of vegf. Electrophoretic mobility shift assays of adding recombinant Smad proteins to the SBE-containing DNA oligonucleotides that represent portions of zebrafish vegf promoter resulted in mobility shift of the oligonucleotides. These changes demonstrate potential interactions between Smad1/5 and the vegf promoter. Reporter activity assays using the wild-type or SBE-deleted vegf promoters to drive the luciferase reporter ...
The murine 3T3-L1 fibroblast under appropriate incubation conditions differentiates into an adipocyte phenotype. This 3T3-L1 adipocyte exhibits many of the morphologic, biochemical, and insulin-responsive features of the normal rodent adipocyte. Using quantitative electron microscopic (EM) autoradiography we find that, when /sup 125/I-insulin is incubated with 3T3-L1 adipocytes, the ligand at early times of incubation localizes to the plasma membrane of the cell preferentially to microvilli and coated pits. When the incubation is continued at 37 degrees C, /sup 125/I-insulin is internalized by the cells and preferential binding to the villous surface is lost. With the internalization of the ligand, two intracellular structures become labeled, as determined by the method of hypothetical grain analysis. These include large clear, presumably endocytotic, vesicles and multivesicular bodies. Over the first hour of incubation the labeling of these structures increases in ...
In view of the findings that several Kunitz-type protein inhibitors suppress tumor invasion and metastasis, the aim of the present study is to explore whether Bungarus multicinctus protease inhibitor-like protein-2 (PILP-2) and PILP-3 exhibit anti-tumor activity. Although approximately 28% of amino acid substitutions occurred between PILP-2 and PILP-3, molecular modeling suggested that PILP-2 and PILP-3 shared similar folded structures. Unlike PILP-2, PILP-3 showed a notable activity in abolishing migration and invasion of human neuroblastoma SK-N-SH cells. The ability of PILP-3 to inhibit matrix metalloprotease-2 (MMP-2) activity was higher than that of PILP-2. Pull-down assay revealed protein-protein interaction between PILP-3 and MMP-2. In contrast to mutation on N-terminal region, replacement of amino acids at C-terminus attenuated notably the ability of PILP-3 to inhibit cell invasion, cell migration and MMP-2 activity as well as the ...
Outbreaks of disease attributable to human error or natural causes can provide unique opportunities to gain new information about host-pathogen interactions and new leads for pathogenesis research. Poststreptococcal glomerulonephritis (PSGN), a sequela of infection with pathogenic streptococci, is a common cause of preventable kidney disease worldwide. Although PSGN usually occurs after infection with group A streptococci, organisms of Lancefield group C and G also can be responsible. Despite decades of study, the molecular pathogenesis of PSGN is poorly understood. As a first step toward gaining new information about PSGN pathogenesis, we sequenced the genome of Streptococcus equi subsp. zooepidemicus strain MGCS10565, a group C organism that caused a very large and unusually severe epidemic of nephritis in Brazil. The genome is a circular chromosome of 2,024,171 bp. The genome shares extensive gene content, including many virulence factors, with genetically ...
Ab initio total energy calculations within the framework of density functional theory have been performed for water molecule adsorption on the (0001) surface of double hexagonal packed americium using a full-potential all-electron linearized augmented plane wave plus local orbitals method (FP-L/APW+lo). Subsequent partial dissociation (OH+H) and complete dissociation (H+O+H) of the water molecule have been examined. The completely dissociated H+O+H configuration exhibit the strongest binding with the surface (3.35 eV), followed by partially dissociated species OH+H (2.23 eV), with all molecular H_2O configurations showing weak physisorption (0.366 eV). For molecular adsorptions, the flat lying orientation of the water molecule if found to be more favorable for majority of the cases. In the case of partial dissociation (OH+H), the vertical orientation of OH molecule with O facing the surface adsorbed at a h3 adsorption site and the H atom adsorbed at another ...
The interaction between two metals, which can be either synergistic or antagonistic, implies that the behavior of one is changed by the presence of the other. Possible mechanisms of these interactions,...Full Text Available
The pharmacology of the alpha-2 adrenoceptor of the human adipocyte was improved by using some new alpha-2 antagonists from different chemical families (imidazolines, benzazepines and benzofuroquinolizines) in biological and binding assays. Moreover, investigations were also carried out to define the binding properties of a new imidazolinic antagonist, RX821002 (2-(2-methoxy-1,4-benzodioxan-2yl)-2-imidazoline), which could be a potential radioligand. (3H)RX821002 binding was very rapid and reversible. Saturation isotherms indicated that (3H)RX821002 labeled, with high affinity, a homogeneous population of noninteracting binding sites with a mean Kd of 0.98 +/- 0.05 nM (n = 6). The binding of (3H)RX821002 on the human fat cell alpha-2 adrenoceptor displayed a specificity which is strictly similar to that obtained with (3H)rauwolscine and which is classical for an alpha-2 A ...
By improving the currently used lactoperoxidase method, we were able to obtain radioiodinated chicken luteinizing hormone (LH) that shows high specific binding and low nonspecific binding to a crude plasma membrane fraction of testicular cells of the domestic fowl and the Japanese quail, and to the ovarian granulosa cells of the Japanese quail. The change we made from the original method consisted of (1) using chicken LH for radioiodination that was not only highly purified but also retained a high receptor binding potency; (2) controlling the level of incorporation of radioiodine into chicken LH molecules by employing a short reaction time and low temperature; and (3) fractionating radioiodinated chicken LH further by gel filtration using high-performance liquid chromatography. Specific radioactivity of the final {sup 125}I-labeled chicken LH preparation was 14 microCi/micrograms. When specific binding ...
Although the subtrate binding properties of adenylate kinase (AK) have been studied extensively by various biochemical and biophysical techniques, it remains controversial whether uncomplexed adenosine 5'-triphosphate (ATP) binds to the adenosine 5'-monophosphate (AMP) site of AK. The authors present two sets of experiments which argue against binding of ATP to the AMP site. (a) /sup 31/P nuclear magnetic resonance titration of ATP with AK indicated a 1:1 stoichiometry on the basis of changes in coupling constants and line widths. This ruled out binding of ATP to both sites. (b) ATP and MgATP were found to behave similarly by protecting AK from spontaneous inactivation while AMP showed only a small degree of protection. Such inactivation could also be protected or reversed by dithioerythritol and is most likely due to oxidation of sulfhydryl groups, one of which (cysteine-25) is ...
Aim: There has been a great demand for developments of the radioligands to visualize the N-methyl-D-aspartate (NMDA) receptors by PET/SPECT. We have recently synthesized two C-11 labeled antagonists for the glycine-binding site on NMDA receptors. The aim of this work is to examine for their in vitro and in vivo binding characteristics, and to evaluate their potentials as PET radioligands for the NMDA receptors. Materials and methods: Two C-11 labeled 4-hydroxy-2-quinolones (1 and 2) were synthesized by conventional methylation of the corresponding phenols with ["1"1C]methyl iodide. In vitro and ex vivo quantitative autoradiographs with imaging plate, as well as animal PET, were employed in order to evaluate their in vitro and in vivo binding to the NMDA receptors. Results: The compound 1 showed the specific binding to rat brain slices with higher localization in the hippocampus and cerebral cortex than ...
The receptor-associated protein (RAP) is a molecular chaperone that binds tightly to certain newly synthesized LDL receptor family members in the endoplasmic reticulum (ER) and facilitates their delivery...Full Text Available
Coordination of CoCl2 solutions to the silica polyamine composite, WP-1, made with the branched polymer polyethylenimine (PEI) shows irreversible binding resulting from surface oxidation of the Co2+-Co3+. This is not the case for the silica polyamine composite BP-1 made with the linear polymer polyallylamine where reversible binding and no oxidation is observed. These observations suggested that oxidation of the cobalt was related to the greater coordination number available with the branched polyamine relative to the linear polyamine. A study of the kinetics of cobalt binding to WP-1 indicated initial loading of Co2+ at relatively low coordination number followed by desorption of Co2+ leading to oxidation and irreversible binding. Exclusion of oxygen from the composite-cobalt solution mix...
BackgroundTacrolimus (FK-506) is an immunosuppressant that binds to a specific immunophilin, resulting in the suppression of the cellular immune response during transplant rejection....Full Text Available
Existing oil reservoirs might be more fully exploited if the properties of the flow of oil and water in porous media were better known. In laboratory experiments it is important to collect as much information as possible to make a descriptive model of the system, including position imaging and chemical binding information. This thesis develops nuclear methods for obtaining position image and chemical binding information from flow experiments of porous media. A combined positron emission tomography and single photon emission computed tomography system to obtain position images, and a time-differential perturbed angular correlation system to obtain chemical binding information, have been built and thoroughly tested. 68 refs., 123 figs., 14 tabs.
Within the framework of the effective-mass approximation, using a variational method, we have calculated the effect of intense laser radiation on the binding energy of the shallow-donor impurities in a Ga1- x In x N y As1- y /GaAs single quantum well for different nitrogen and indium mole concentrations. Our numerical results show that the binding energy strongly depends on the laser intensity and frequency (via the laser dressing parameter) and it also depends on the nitrogen and indium concentrations. Impurity binding energy under intense laser fields can be tuned by changing the nitrogen and indium mole fraction.
This paper describes attempts to isolate and characterize glycosaminoglycan (GAG)-binding molecules on the surface of lymphocytes and lymphoma cell lines and relate their expression to splenic and lymph...Full Text Available
Carbohydrate-directed endocytosis is mediated by a receptor, the hepatic binding protein; it is responsible for the clearance of galactose-terminated glycoproteins from the circulation. This process...Full Text Available
The cAMP response element-binding protein (CREB) is a highly conserved transcription factor that integrates signaling through the cAMP-dependent protein kinase A (PKA) in many eukaryotes. PKA plays a critical role in Dictyostelium development but no CREB homologue has been identified in this system. Here we show that Dictyostelium utilizes a CREB-like protein, BzpF, to integrate PKA signaling during late development. bzpF^- mutants produce compromised spores, which are extremely unstable and germination defective. Previously, we have found that BzpF binds the canonical CRE motif in vitro. In this paper, we determined the DNA binding specificity of BzpF using protein binding microarray (PBM) and showed that the motif with the highest specificity is a CRE-like sequence. BzpF is necessary to ...
A fundamental study of the application of bacteria to the recovery of toxic heavy metals from aqueous environments was carried out. The biosorption characteristics of cadmium and lead ions were determined with purple nonsulfur bacteria, Rhodobacter sphaeroides and hydrogen bacteria, Alcaligenes eutrophus H16 that were inactivated by steam sterilization. A simplified version of the metal binding model proposed by Plette et al. was used for the description of meal binding data. The results showed that the biosorption of bivalent metal ions to whole cell bodies of the bacteria was due to monodentate binding to two different types of acidic sites: carboxilic and phosphatic-type sites. The number of metal binding sites of A. eutrophus was 2.4-fold larger than that of R. sphaeroides.
The synthesis of (/sup 14/C)-10,11-Epoxy-(2E,6E)-farnesyl diazoacetate in one vessel, starting from (/sup 14/C)-glyoxylic acid, is described. This compound is useful as a potential photoaffinity labeling agent for juvenile hormone binding sites.
The authors have localized and characterized 2-125I-iodomelatonin binding sites in the chicken brain using in vitro quantitative autoradiography. Binding sites were widely distributed throughout the chicken brain, predominantly in regions associated with the visual system. The specific binding of 2-125I-iodomelatonin to discrete chicken brain areas was found to be saturable, reversible, and of high affinity. The specific binding of 2-125I-iodomelatonin (75 pm) was quantitated for 40 identifiable brain regions. Eight brain regions were chosen for binding characterization and pharmacological analysis: optic tectum, Edinger-Westphal nucleus, oculomotor nucleus, nucleus rotundus, ventral supraoptic decussation, ventrolateral geniculate nucleus, neostriatum, and ectostriatum. These regions showed no rostral-caudal gradient in 2-125I-iodomelatonin specific binding, ...
Sterol regulatory element-binding protein (SREBP)-1 is a key transcription factor for the regulation of lipogenic enzyme genes in the liver. Polyunsaturated fatty acids (PUFA) selectively suppress hepatic...Full Text Available
Seventeen clinical isolates of Staphylococcus aureus (from the United States and Europe) selected for low (borderline)-level methicillin resistance (MIC of methicillin, 2 to 4 micrograms/ml; MIC of...Full Text Available
The amino acid residues 114-118 in actin were found to be implicated strongly in the binding of nucleotide, and as would be expected for such an important binding site, they are located in a completely conserved region of the actin sequence. A 19-residue peptide with the actin sequence 106-124 was synthesized in order to span the putative triphosphate binding site. Proton NMR spectra of the actin peptide 114-118 in the presence and absence of ATP indicated that Arg-116 and Lys-118 are particularly involved in binding ATP. A strong binding of ATP to the peptide 106-124 also was measured. Tripolyphosphate bound to the peptide 106-124 somewhat more weakly than ATP. Binding involved residues 115-118 and 121-124, indicating the presence of a reverse turn between these segments. Proton resonances were assigned by using two-dimensional double quantum correlated ...
The CCAAT/enhancer-binding protein β (C/EBPβ) is required for adipocyte differentiation and maturation. We have studied the role of the transcription factor, C/EBPβ,...Full Text Available
The discovery of a specific high-affinity growth hormone (GH) binding protein (GH-BP) in plasma adds complexity to the dynamics of GH secretion and clearance. Intuitive predictions are that such a protein...Full Text Available
The PbII binding characteristics of the previously reported PbII binding proteins of rat kidney cytosol were investigated further. Saturation and Scatchard analysis of /sup 203/Pb binding in whole cytosol and in 40% saturated ammonium sulfate precipitated fractions disclosed a class of relatively high-affinity sites with an apparent Kd of approximately 50 nM and binding capacities of approximately 41 and 9 pmol/mg of protein, respectively. Two /sup 203/Pb binding proteins with approximate molecular masses of 63K and 11.5K daltons and a high molecular weight component (greater than 200K) were isolated by Sepharose-6B column chromatography. The time course of association of /sup 203/Pb with cytosol and the 63K protein showed maximum binding at 18 hr which was stable up to 25 hr at 4 degrees C. The approximate half-time dissociation rate (T 1/2) of specifically ...
The PbII binding characteristics of the previously reported PbII binding proteins of rat kidney cytosol were investigated further. Saturation and Scatchard analysis of "2"0"3Pb binding in whole cytosol and in 40% saturated ammonium sulfate precipitated fractions disclosed a class of relatively high-affinity sites with an apparent Kd of approximately 50 nM and binding capacities of approximately 41 and 9 pmol/mg of protein, respectively. Two "2"0"3Pb binding proteins with approximate molecular masses of 63K and 11.5K daltons and a high molecular weight component (greater than 200K) were isolated by Sepharose-6B column chromatography. The time course of association of "2"0"3Pb with cytosol and the 63K protein showed maximum binding at 18 hr which was stable up to 25 hr at 4 degrees C. The approximate half-time dissociation rate (T 1/2) of specifically bound ...
The protein binding of diazepam (D) and its major active metabolite N-desmethyl diazepam (DD) was investigated in vitro in the serum of 14 mothers at birth, 21 foetuses at birth, in 100 neonates between...Full Text Available
1 The decreased binding of drugs and dyes to plasma proteins from male and female rats with acute renal failure has been investigated using equilibrium dialysis at 37 degrees C. 2 Acute renal failure...Full Text Available
The DNA-binding properties of Ru(bpy)2(eilatin)2+ have been investigated to determine if the sterically expansive eilatin ligand confers specificity for destabilized single-base...Full Text Available
Basic fibroblast growth factor (bFGF) exhibits specific binding to the extracellular matrix (ECM) produced by cultured endothelial cells. Binding was saturable as a function both of time and of concentration of {sup 125}I-bFGF. Scatchard analysis of FGF binding revealed the presence of about 1.5 x 10{sup 12} binding sites/mm{sup 2} ECM with an apparent k{sub D} of 610 nM. FGF binds to heparan sulfate (HS) in ECM as evidenced by (i) inhibition of binding in the presence of heparin or HS at 0.1-1 {mu}g/mL, but not by chondroitin sulfate, keratan sulfate, or hyaluronic acid at 10 {mu}g/mL, (ii) lack of binding to ECM pretreated with heparitinase, but not with chondroitinase ABC, and (iii) rapid release of up to 90% of ECM-bound FGF by exposure to heparin, HS, or heparitinase, but not to chondroitin sulfate, keratan sulfate, hyaluronic acid, or ...
This study focuses on the effects of long-term renin-angiotensin system suppression and/or incretin mimetic therapies on the regulation and binding affinity of GLP-1 to its receptor in the coronary...Full Text Available
Epidermal growth factor (EGF) stimulates adenylyl cyclase in the heart via activation of the stimulatory GTP-binding protein Gs. Therefore, employing peptides corresponding to regions in the cytosolic...Full Text Available
Ingestion or inhalation of botulinum neurotoxin (BoNT) results in botulism, a severe and frequently fatal disease. Current treatments rely on antitoxins, which while effective cannot reverse...Full Text Available
Suicide substrate β, γ-bidentate Rh(III)ATP (RhATP) was used to map the metal ion-binding site in yeast phosphoglycerate kinase (PGK). Cleavage of the RhATP-inactivated enzyme with...Full Text Available
GSTD1 is one of several insect glutathione S-transferases capable of metabolizing the insecticide DDT. Here we use crystallography and NMR to elucidate the binding of DDT and glutathione to GSTD1. The crystal structure of Drosophila melanogaster GSTD1 has been determined to 1.1 {angstrom} resolution, which reveals that the enzyme adopts the canonical GST fold but with a partially occluded active site caused by the packing of a C-terminal helix against one wall of the binding site for substrates. This helix would need to unwind or be displaced to enable catalysis. When the C-terminal helix is removed from the model of the crystal structure, DDT can be computationally docked into the active site in an orientation favoring catalysis. Two-dimensional {sup 1}H,{sup 15}N heteronuclear single-quantum coherence NMR experiments of GSTD1 indicate that conformational changes occur upon glutathione and DDT binding and the residues that ...
Ex vivo (/sup 3/H)-8-hydroxy-2-(di-n-propylamino)-tetraline ((/sup 3/H)-DPAT) binding to the hippocampus has been utilized to determine the pharmacokinetic parameters of buspirone after i.v. and oral administration of this drug to rats. Intravenous buspirone rapidly penetrated the brain as demonstrated by a maximum inhibition of (/sup 3/H)-DPAT binding at 1 min. Elimination of drug from the brain was biphasic, with a first component half-life of 24.8 min and a second component half-life of 96 min. Oral buspirone at 3 times the i.v. dose produced less than one-third the maximum inhibition of (/sup 3/H)-DPAT binding compared to that observed with i.v. buspirone. The pharmacokinetic parameters of buspirone observed in the present study are in agreement with those reported previously. Thus, the ex vivo binding assay could be utilized to determine the bioavailability of the drug to the brain, and its ...
Zinc-fingers, which widely exist in eukaryotic cell and play crucial roles in life processes, depend on the binding of zinc ion for their proper folding. To computationally study the zinc coupled folding of the zinc-fingers, charge transfer and metal induced protonation/deprotonation effects have to be considered. Here, by attempting to implicitly account for such effects in classical molecular dynamics and performing intensive simulations with explicit solvent for the peptides with and without zinc binding, we investigate the folding of the Cys2His2 type zinc-finger motif and the coupling between the peptide folding and zinc binding. We find that zinc ion not only stabilizes the native structure, but also participates in the whole folding process. It binds to the peptide at early stage of folding, and directs or modulates the folding and stabilizations of the component beta-hairpin and alpha-helix. ...
Human erythrocyte glucose-6-phosphate is normally quite stable in the presence of 10 #mu#M NADP"+. Certain glucose-6-phosphate dehydrogenase variants lose virtually all their activity at this concentration of NADP"+ but are reactivated by 200 #mu#M NADP"+. Such variants presumably have a defect in their NADP"+-binding site. The authors analyzed the sequence of cDNA or genomic DNA from seven unrelated patients with hemolytic anemia due to the inheritance of variants that are reactivated by NADP"+. Six patients had substitutions of one of three adjacent amino acids, and the seventh patient had another amino acid substitution 23 residues downstream. These amino acids are highly conserved, all being present in rat and all but one being found also in Drosophila. The anomalous electrophoretic behavior of some of the variants can be explained by their loss of ability to bind NADP"+. The conclude that the region in which these mutations occur defines ...
The effects of atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) on guanylate cyclase activity and cyclic GMP accumulation were examined, since these hormones appear to be intimately associated with blood pressure and intravascular volume homeostasis. ANP was found to increase cyclic GMP accumulation in ten cell culture systems, which were derived from blood vessels, adrenal cortex, kidney, lung, testes and mammary gland. ANP receptors were characterized in intact cultured cells using {sup 125}I-ANP{sub 8-33}. Specific {sup 125}I-ANP binding was saturable and of high affinity. Scratchard analysis of the binding data for all cell types exhibited a straight line, indicating that these cells possessed a single class of binding sites. Despite the presence of linear Scatchard plots, these studies demonstrated that cultured cells possess two functionally and physically distinct ANP-binding ...
The study of interaction of tachyons with superluminal electromagnetic fields has been undertaken and it has been shown that the energy of this interaction is similar to that of bradyons with ordinary electromagnetic fields except that the roles of virtual and longitudinal parts are interchanged. It has also been shown that the interaction of tachyons with superluminal electromagnetic fields in time-energy representation is identical to the interaction of bradyons with ordinary electromagnetic fields in space-momentum representation. 19 references.
The study of interaction of tachyons with superluminal electromagnetic fields has been undertaken and it has been shown that the energy of this interaction is similar to that of bradyons with ordinary electromagnetic fields except that the roles of virtual and longitudinal parts are interchanged. It has also been shown that the interaction of tachyons with superluminal electromagnetic fields in time-energy representation is identical to the interaction of bradyons with ordinary electromagnetic fields in space-momentum representation. (author).
In previous work the authors showed that on photolysis of Escherichia coli ribosomes in the presence of ({sup 3}H)tetracycline (TC) the major protein labeled is S7, and they presented strong evidence that such labeling takes place from a high-affinity site related to the inhibitory action of TC. In this work they use single protein omission reconstitution (SPORE) experiments to identify those proteins that are important for high-affinity TC binding to the 30S subunit, as measured by both cosedimentation and filter binding assays. With respect to both sedimentation coefficients and relative Phe-tRNA{sup Phe} binding, the properties of the SPORE particles they obtain parallel very closely those measured earlier, with the exception of the SPORE particle lacking S13. A total of five proteins, S3, S7, S8, S14, and S19, are shown to be important for TC binding, with the largest effects seen on omission of ...
(3H)Cyclofoxy (CF: 17-cyclopropylmethyl-3,14-dihydroxy-4,5-alpha-epoxy-6-beta-fluoromorp hinan) is an opioid antagonist with affinity to both mu and kappa subtypes that was synthesized for quantitative evaluation of opioid receptor binding in vivo. Two sets of experiments in rats were analyzed. The first involved determining the metabolite-corrected blood concentration and tissue distribution of CF in brain 1 to 60 min after i.v. bolus injection. The second involved measuring brain washout for 15 to 120 s following intracarotid artery injection of CF. A physiologically based model and a classical compartmental pharmacokinetic model were compared. The models included different assumptions for transport across the blood-brain barrier (BBB); estimates of nonspecific tissue binding and specific binding to a single opiate receptor site were found to be essentially the same with both models. The nonspecific ...
Radiation inactivation and sedimentation equilibrium analysis were used to determine the functional and physical size of the chicken hepatic membrane receptor that binds N-acetylglucosamine-terminated glycoproteins. Purified plasma membranes from chicken liver were irradiated with high energy electrons and assayed for 125I-agalactoorosomucoid binding. Increasing the dose of ionizing radiation resulted in a monoexponential decay in binding activity due to a progressive loss of binding sites. The molecular mass of the chicken lectin, determined in situ by target analysis, was 69,000 +/- 9,000 Da. When the same irradiated membranes were solubilized in Brij 58 and assayed, the binding protein exhibited a target size of 62,000 +/- 4,000 Da; in Triton X-100, the functional size of the receptor was 85,000 +/- 10,000 Da. Sedimentation equilibrium measurements of the purified ...
In-vitro experiments using "2"0"3Pb were performed to identify the lead binding components in human peripheral blood. The distribution of lead in plasma, in the red cell membrane, and within the red cell was also investigated. Studies of the distribution of "2"0"3Pb in the whole blood showed that at a lead concentration of 2.45 #mu#mol/l (50 #mu#g/100 ml) about 94% of lead had been incorporated by the erythrocytes and 6% remained in the plasma. After extraction of lipid by a methanol/chloroform mixture, about 75% of the lead was found to be associated with the protein fraction. The lipid contained about 21% of the "2"0"3Pb, the remainder being in the aqueous plasma. SDS polyacrylamide gel electrophoresis of blood plasma showed that almost 90% of the "2"0"3Pb was present in the albumin fraction; the remainder was likely to be associated with high molecular weight globulins. Several binding sites were identified on the erythrocyte membrane. The ...
Background The identification of sequences that control transcription in metazoans is a major goal of genome analysis. In a previous study, we demonstrated that searching for clusters of predicted transcription factor binding sites could discover active regulatory sequences, and identified 37 regions of the Drosophila melanogaster genome with high densities of predicted binding sites for five transcription factors involved in anterior-posterior embryonic patterning. Nine of these clusters overlapped known enhancers. Here, we report the results of in vivo functional analysis of 27 remaining clusters. Results We generated transgenic flies carrying each cluster attached to a basal promoter and reporter gene, and assayed embryos for reporter gene expression. Six clusters are enhancers of adjacent genes: giant, fushi tarazu, odd-skipped, nubbin, squeeze and pdm2; three drive expression in patterns unrelated to those of neighboring genes; the ...
Materials and MethodsThe genomic effects of tumor-endothelial interactions in cancer are not yet well characterized. To study this interaction in breast...Full Text Available
Large quantity of reliable protein interaction data are available for model organisms in public depositories (e.g., MINT, DIP, HPRD, INTERACT). Most data correspond to experiments with the proteins...Full Text Available
In the CNS, there are widespread and diverse interactions between growth factors and estrogen. Here we examine the interactions of estrogen and brain-derived neurotrophic factor (BDNF), two...Full Text Available
The binding energy parameter #lambda# plays an important role in common envelope evolution. Previous works have already pointed out that #lambda# varies throughout the stellar evolution, though it has been adopted as a constant in most of the population synthesis calculations. We have systematically calculated the binding energy parameter #lambda# for both Population I and Population II stars of masses 1-20 M _s_u_n, taking into account the contribution from the internal energy of stellar matter. We present fitting formulae for #lambda# that can be incorporated into future population synthesis investigations. We also briefly discuss the possible applications of the results in binary evolutions.
Ab initio planewave pseudopotential method is used to study carbon diffusion and pairing in crystalline silicon. The calculation is performed with a 40 Ry planewave cutoff and 2x2x2 special k-point sampling with a supercell of 64 atoms. It is found that substitutional carbon attracts interstitial Si forming a <001> C interstitial with a large binding energy of 1.45 eV. The interstitial carbon is mobile and can migrate with a migration energy of 0.5 eV. The interstitial carbon can bind further to another substitutional carbon forming a substitutional carbon-interstitutional carbon pair with a binding energy of 1.0 eV. This model is used to understand the effect of high C concentration on the transient enhanced diffusion in Si.
This paper describes a thermodynamic analysis of multivalent interactions, with the goal of clarifying the influence of the linker on the enhancement in avidity due to multivalency. The use...Full Text Available
4) Expand to include client-server interaction (small-scale archive interactions with the goal of evaluating information management capabilities) -- Early ...
A remarkable aspect of the interaction of Cryptococcus neoformans with mammalian hosts is a consistent increase in capsule volume. Given...Full Text Available
NSF-NIST Interaction in Chemistry, Materials Research, Molecular Biosciences, Bioengineering, and ... Laboratory (CSTL). Materials research is centralized in the Materials Science and Engineering ...
We present interactive computer programs for the analysis of nucleic acid sequences. In order to handle these programs, minimum computer experience is sufficient. The nucleotide sequence of the human...Full Text Available
Global acetylation of histone H4 is a mark of gene transcriptional activation. The c-Myc transcription factor binds to specific DNA sites in cellular chromatin and induces the acetylation of...Full Text Available
BackgroundHarbour porpoises Phocoena phocoena from the southern North Sea are known to display high levels of Zn and Hg in their tissues linked to their nutritional...Full Text Available
The hemagglutinin (HA) glycoprotein of influenza virus performs two critical roles during infection: it binds virus to cell surface sialic acids, and under mildly acidic conditions it induces fusion...Full Text Available
ObjectivesThe aim of this study was to assess the diagnostic and prognostic value of heart-type fatty acid-binding protein (H-FABP) in elective percutaneous coronary intervention...Full Text Available
San Francisco Bay has been contaminated historically by mercury from mine tailings as well as contemporary industrial sources. Native Spartina foliosa and non-native S....Full Text Available
The acyl coenzyme A (CoA) binding protein AcbA is secreted unconventionally and processed into spore differentiation factor 2 (SDF-2), a peptide that coordinates sporulation in Dictyostelium...Full Text Available
Many bacterial pathogens produce extracellular proteases that degrade the extracellular matrix of the host and therefore are involved in disease pathogenesis. Dichelobacter nodosus...Full Text Available
Sucrose phosphate synthase (SPS) catalyzes the transfer of a glycosyl group from an activated donor sugar, such as uridine diphosphate glucose (UDP-Glc), to a saccharide acceptor D-fructose 6-phosphate (F6P), resulting in the formation of UDP and D-sucrose-6'-phosphate (S6P). This is a central regulatory process in the production of sucrose in plants, cyanobacteria, and proteobacteria. Here, we report the crystal structure of SPS from the nonphotosynthetic bacterium Halothermothrix orenii and its complexes with the substrate F6P and the product S6P. SPS has two distinct Rossmann-fold domains with a large substrate binding cleft at the interdomain interface. Structures of two complexes show that both the substrate F6P and the product S6P bind to the A-domain of SPS. Based on comparative analysis of the SPS structure with other related enzymes, the donor substrate, nucleotide diphosphate glucose, binds to the ...
The specific binding of transcription factors to cognate sequence elements is thought to be critical for the generation of specific gene expression programs. Members of the nuclear factor κB...Full Text Available
The RNA-binding protein Hfq is recognized as an important regulatory factor in a variety of cellular processes, including stress resistance and pathogenesis. Hfq has been shown in several bacteria to...Full Text Available
Peptide toxins with high affinity, divergent pharmacological functions, and isoform-specific selectivity are powerful tools for investigating the structure-function relationships of voltage-gated...Full Text Available
Dal82p binds to the UISALL sites of allophanate-induced genes of the allantoin-degradative pathway and functions synergistically with the GATA family Gln3p and Gat1p transcriptional...Full Text Available
The second messenger signaling molecule bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) regulates many processes in bacteria, including motility, pathogenesis,...Full Text Available
On rod disc membranes, single photoactivated rhodopsin (R*) molecules catalytically activate many copies of the G-protein (Gt), which in turn binds and activates the effector (phosphodiesterase). We...Full Text Available
MicroRNAs (miRNAs) are short non-coding RNAs that play a central role in regulation of gene expression by binding to target genes. Many miRNAs were associated with the function of the central nervous...Full Text Available
The length polymorphism of the serotonin (5-HT) transporter gene promoter region has been implicated in altered 5-HT function and, in turn, neuropsychiatric illnesses, such as anxiety and depression....Full Text Available
The intracellular bioavailability of lead (Pb) at low dosage levels in major target organs such as the kidney and brain appears to be largely determined by complexation with a group of low molecular...Full Text Available
The sequence information available for homeodomains reveals that salt bridges connecting pairs 19/30, 31/42, and 17/52 are frequent, whereas aliphatic residues at these sites are rare and mainly restricted...Full Text Available
We examined the changes in the levels of indoleacetic acid (IAA), IAA esters, and a 22-kilodalton subunit auxin-binding protein (ABP1) in apical mesocotyl tissue of maize (Zea mays...Full Text Available
The presence of albumin structures with the capacity to bind to a surface receptor in group C and G streptococci was studied in serum samples from 45 mammalian species representing 15 different orders,...Full Text Available
The radiation method has been employed for the modification of the surface of vascular prostheses by means of acrylamide. As a result of the treatment, the tightness of the prosthesis walls was improved as well as an increase of surface hydrophilicity. Upon autoclaving, stable binding of polyacrylamide to prostheses is achieved. (author).
The in situ assembly states of the glucose transport carrier protein in the plasma membrane and in the intracellular (microsomal) storage pool of rat adipocytes were assessed by studying radiation-induced inactivation of the D-glucose-sensitive cytochalasin B binding activities. High energy radiation inactivated the glucose-sensitive cytochalasin B binding of each of these membrane preparations by reducing the total number of the binding sites without affecting the dissociation constant. The reduction in total number of binding sites was analyzed as a function of radiation dose based on target theory, from which a radiation-sensitive mass (target size) was calculated. When the plasma membranes of insulin-treated adipocytes were used, a target size of approximately 58,000 daltons was obtained. For adipocyte microsomal membranes, we obtained target sizes of approximately 112,000 and 109,000 daltons prior ...
Binding of epidermal growth factor (EGF) to the EGF receptor (EGFR) initiates signal transduction, ultimately leading to altered gene expression. Ligand-activated EGFR is also rapidly internalized...Full Text Available
A single radial hemolysis test was developed for quantitation of specific antibody to non-hemagglutinating viruses. With the human coronaviruses as models, this test utilizes the binding properties...Full Text Available
mRNA guanylyltransferase has been extensively purified from calf thymus. A GTP-binding assay was used based on the observations by Shuman and Hurwitz (1981) and Venkatesan and Moss (1982) that vaccinia...Full Text Available
BackgroundBaculovirus, which has a width of 40 nm and a length of 250-300 nm, can display functional peptides, receptors and antigens on its surface by their fusion with a baculovirus...Full Text Available
In Chlamydomonas reinhardtii y-1, newly synthesized chlorophyll a/b-binding apoproteins are degraded when chlorophylls are not present for assembly of stable light-harvesting...Full Text Available
BackgroundThe lactogenic hormones prolactin (PRL) and placental lactogens (PL) play central roles in reproduction and mammary development. Their actions are mediated via binding...Full Text Available
BackgroundThe dystrophin glycoprotein complex is disrupted in Duchenne muscular dystrophy and many other neuromuscular diseases. The principal heterodimeric partner of dystrophin...Full Text Available
How transcription factors interpret the cis-regulatory logic encoded within enhancers to mediate quantitative changes in spatiotemporally restricted expression patterns during animal...Full Text Available
1 Measuring total plasma levels of disopyramide (DP) and the main metabolite mono-N-dealkyldisopyramide (MND) in patients on maintenance therapy with DP has shown concentrations of MND comparable with...Full Text Available
Edema factor (EF) and CyaA are calmodulin (CaM)-activated adenylyl cyclase exotoxins involved in the pathogenesis of anthrax and whooping cough, respectively. Using spectroscopic, enzyme kinetic and...Full Text Available
Type 1 pilus directs bladder epithelial binding and invasion by uropathogenic Escherichia coli (UPEC) in the initial stage of cystitis, but the bacterial determinants of postinvasion...Full Text Available
PurposeTo report unusual ocular manifestations of branchio-oculo-facial syndrome (BOFS) caused by a novel mutation in activating enhancer binding protein 2 alpha (TFAP2A).MethodsFull...Full Text Available
The nucleocapsid protein (NC) of retroviruses plays a major role in genomic RNA packaging, and some evidence has implicated the matrix protein (MA) of certain retroviruses in viral RNA binding. To further...Full Text Available
Up-flow anaerobic attached-growth bioreactors filled with pre-treated coir fibres ...coir-fibre arranged in bottle-brush configuration bounded by a novel plastic binding technique ...-three anaerobic filter reactors in series -coir fibre as the bacteria growth media a sedimentation
The sequence-dependent structural variability and conformational dynamics of DNA play pivotal roles in many biological milieus, such as in the site-specific binding of transcription factors to target...Full Text Available
The X-ray crystallographic structural determinations of synthetic estrogens and antiestrogens provide reliable information on the global minimum energy conformation of these molecules or a local minimum...Full Text Available
The Far UpStream Element (FUSE) regulatory system promotes a peak in the concentration of c-Myc during cell cycle. First, the FBP transcriptional activator binds to the FUSE DNA element upstream...Full Text Available
We have developed miniature (≈1 μm diameter) microcavity surface-plasmon-resonance sensors (MSPRS), integrated them with microfluidics and tested...Full Text Available
Our goal was to determine whether chlorpyrifos oxon, dichlorvos, diisopropylfluorophosphate (DFP), and sarin covalently bind to human albumin. Human albumin or plasma was treated with organophosphorus...Full Text Available
The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D3-binding protein-derived macrophage-activating factor (DBPMAF) was examined using a mouse SCCVII...Full Text Available
SummaryThe general transcription factor TFIID is a large multi-subunit complex required for the transcription of most protein-encoding genes by RNA polymerase II. Taking advantage...Full Text Available
Mammals possess multiple insulin-like growth factor (IGF) binding proteins (IGFBPs), and related proteins, that modulate the activity of insulin/IGF signalling (IIS), a conserved neuroendocrine signalling...Full Text Available
Dysregulation of the alternative pathway of complement activation, caused by mutations or polymorphisms in the genes encoding factor H, membrane co-factor protein, factor I or factor B, is associated...Full Text Available
Cdc13 is a single stranded telomere binding protein that specifically localizes to the telomere ends of budding yeasts and is essential for cell viability. It caps the ends of chromosomes thus preventing...Full Text Available
Local anesthetics are able to induce pain relief by binding to the sodium channels of excitable membranes, blocking the influx of sodium ions and the propagation of the nervous impulse. Ropivacaine...Full Text Available
Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) allows researchers to determine the genome-wide binding locations of individual transcription factors (TFs) at high resolution....Full Text Available
To gain insight into ATP-binding cassette transporter A1 (ABCA1) function and its potential role in AD pathology, we analyzed the expression of the cholesterol transporter ABCA1...Full Text Available
Over 200 mutations in the retina specific member of the ATP-binding cassette transporter super-family (ABCA4) have been associated with a diverse group of human retinal diseases....Full Text Available
Acute myocardial infarction (AMI) is a common cause of death for which effective treatments are available provided that diagnosis is rapid. The current diagnostic gold standards are circulating cardiac...Full Text Available
Human complement protein C9 is shown to be a metalloprotein that binds 1 mol of Ca"2"+/mol of C9 with a dissociation constant of 3 #mu#m as measured by equilibrium dialysis. Incubation with EDTA removes the bound calcium, resulting in a apoprotein with decreased thermal stability. This loss in stability leads to aggregation and, therefore, to loss of hemolytic activity upon heating to a few degrees above the physiological temperature. Heat-induced aggregation of apoC9 can be prevented by salts that stabilize proteins according to the Hofmeister series of lyotropic ions, suggesting that the ion in native C9 may ligand with more than one structural element of domain of the protein. Ligand blotting indicates that the calcium binding site is located in the amino-terminal half of the protein. Removal of calcium by inclusion of EDTA in assay mixtures has no effect on the hemolytic activity of C9, and its capacity to bind to C8 in ...
Mitochondria must uptake some phospholipids from the endoplasmic reticulum (ER) for the biogenesis of their membranes. They convert one of these lipids, phosphatidylserine, to phosphatidylethanolamine,...Full Text Available
The high-energy reaction cross sections of Li and Be isotopes are calculated using a simplified Glauber model and densities constrained by the empirical binding energies. We find excellent agreement with experiment, reproducing the large increase for the most neutron-rich nuclei.
To analyse the binding of sugar chains to proteins, viruses and cells, the surface plasmon resonance (SPR) technique is very convenient and effective because it is a real-time, non-destructive detection...Full Text Available
In-vitro experiments using 203Pb were performed to identify lead-binding components in human haemoglobin. Sephadex A-50 ion-exchange chromatography of haemolysate showed that different types of haemoglobin...Full Text Available
Moenomycin A (MmA) belongs to a family of natural products that inhibit peptidoglycan biosynthesis by binding to the peptidoglycan glycosyltransferases (PGTs), the enzymes that make the glycan...Full Text Available
To study the expression of Fc receptors in human alveolar macrophages (AM), the cells were collected from 12 healthy controls and 22 patients with sarcoidosis and the activity involved in binding to...Full Text Available
Attention deficit hyperactivity disorder (ADHD) is known as a psychiatric disorder in childhood associated with dopamine dysregulation. We investigated dopamine transporter (DAT) density in children with ADHD in the present study using {sup 123}I-IPT SPECT and postulated that an alteration in DAT density in the basal ganglia (BG) is responsible for dopaminergic dysfunction in children with ADHD. 9 durg-naive children with ADHD and 6 normal children were included in the study. We performed brain SPECT 2 hours after administration of {sup 123}I-IPT and made both quantitative and qualitative analyses for assessment of specific/nonspecific DAT binding ratio in the BG. We investigated the correlation between the severity scores of ADHD symptoms in children with ADHD assessed with ADHD rating scale and specific/nonspecific DAT binding ratio in the BG. Drug-naive children with ADHD showed a significantly incresed specific/nonspecific DAT ...
In-vitro experiments using 203Pb were performed to identify the lead binding components in human peripheral blood. The distribution of lead in plasma, in the red cell membrane, and within the red cell...Full Text Available
The hepatic uptake rate for certain albumin-bound drugs and metabolites correlates poorly with their equilibrium unbound concentration in the plasma, suggesting that binding equilibrium may not always...Full Text Available
BackgroundMicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to the messenger RNA (mRNA) of protein coding genes. They control gene expression by either...Full Text Available
Proteins that metabolize or bind the nucleotide second messenger cyclic diguanylate regulate a wide variety of important processes in bacteria. These processes include motility, biofilm formation, cell...Full Text Available
ATP-binding cassette A3 (ABCA3) is a lipid transport protein required for synthesis and storage of pulmonary surfactant in type II cells in the alveoli. Abca3 was conditionally deleted...Full Text Available
Dicarboxylic acids are prominent features of several diseases, including Reye's syndrome and inborn errors of mitochondrial and peroxisomal fatty acid oxidation. Moreover, dicarboxylic acids are potentially...Full Text Available
Hookworms, bloodfeeding intestinal nematodes, infect nearly one billion people in resource limited countries and are a leading cause of anemia and malnutrition. Like other nematodes, hookworms...Full Text Available
Cd36 is a small-molecular-weight integral membrane protein expressed in a diverse, but select, range of cell types. It has an equally diverse range of ligands and physiological functions, which has...Full Text Available
SummarySpatial control of gene expression, at the level of both transcription and translation, is critical for cellular differentiation [1-Full Text Available
E-cadherins belong to a family of membrane-bound, cellular adhesion proteins. Their adhesive properties mainly involve the two N-terminal extracellular domains (EC1 and EC2). The junctions between these...Full Text Available
BackgroundCardiovascular disease (CVD) is a leading cause of mortality in the United States as well as globally. Epidemiological studies show that regular fruit and vegetable consumption...Full Text Available
BackgroundHealth risk from exposure of perfluorochemicals (PFCs) to wildlife and human has been a subject of great interest for understanding their molecular mechanism of toxicity....Full Text Available
The CD1 family of proteins binds self and foreign glycolipids for presentation to CD1-restricted T cells. To identify previously uncharacterized active CD1 ligands, especially those of microbial origin,...Full Text Available
Familial defective apolipoprotein (apo) B-100 is a genetic disease that leads to hypercholesterolemia and to an increased serum concentration of low density lipoproteins that bind defectively to the...Full Text Available
BackgroundMale infertility is a common cause of reproductive failure in humans. In mice, targeted deletions of the genes coding for FKBP6 or FKBP52, members of the FK506 binding...Full Text Available
Essential in mitosis, the human Kinesin-5 protein is a target for >80 classes of allosteric compounds that bind to a surface-exposed site formed by the L5 loop. Not established is why there...Full Text Available
Albendazole binds to parasite's tubulin inhibiting its glucose absorption. Its common adverse effects are nausea, vomiting, constipation, thirst, dizziness, headache, hair loss and pruritus. Although...Full Text Available
Ataxin-3, the protein involved in Machado-Joseph disease, is able to bind ubiquitylated substrates and act as a deubiquitylating enzyme in vitro, and it has been involved in the modulation of protein...Full Text Available
Endogenous immune complexes present in sera from 10 different patients with systemic lupus erythematosus (SLE) in an active phase were allowed to bind to Raji cells; the ability of intact complement...Full Text Available
Abs facilitate humoral immunity via the classical mechanisms of opsonization, complement activation, Ab-dependent cellular cytotoxicity, and toxin/viral neutralization. There is also evidence that some...Full Text Available
Siderophores are essential factors for iron (Fe) acquisition in bacteria during colonization and infection of eukaryotic hosts, which restrain iron access through iron-binding protein, such as lactoferrin...Full Text Available
The ventromedial hypothalamus (VMH) plays a central role in the regulation of the female reproductive behavior lordosis, a behavior dependent upon the sequential activation of receptors for the ovarian...Full Text Available
A pentapeptide open reading frame equipped with a canonical ribosome-binding site is present in the Escherichia coli 23S rRNA. Overexpression of 23S rRNA fragments containing the mini-gene renders cells...Full Text Available
DNA antoantibodies in serum will bind to antigen-coated polystyrene tubes and can be detected by radiolabelled anti-immunoglobulin. The method is quantitative, gives information on the antibody class...Full Text Available
BackgroundFor the detection of allergen-specific IgE in sera, solid-phase IgE-binding assays like the CAP test are commonly used. Although such immunochemical methods are very sensitive,...Full Text Available
The identification of MHC class II restricted peptide epitopes is an important goal in immunological research. A number of computational tools have been developed for this purpose, but there is a lack...Full Text Available
Gamma interferon (IFN-γ) and the cellular responses induced by it are essential for controlling mycobacterial infections. Most patients bearing an IFN-γ receptor ligand-binding chain...Full Text Available
We have investigated the effect of the rho tensor coupling on binding energies, matter root-mean-square radii and spin orbit splittings of Ca isotopes in the relativistic mean-field theory with sigma, omega, and rho mesons. It is shown that binding energies and matter root-mean-square radii are insensitive to an alteration in the strength of the rho tensor coupling and an explanation of this is given. We have further shown that inclusion of the rho tensor coupling will give isospin-dependent spin-orbit splittings and this will greatly affect spin-orbit splittings of nuclei near the neutron drip line. (author). Letter-to-the-editor.
A new coumarin-based sensor molecule (L1) has been synthesized and this was found to bind calcium and magnesium ions more effectively as compared to other alkali/alkaline earth/lanthanide and certain transition metal ions. A significant enhancement in fluorescence intensity was observed on binding to Ca2+ and Mg2+ ions; while a minor quenching was observed for weakly bound Hg2+, Ni2+, Fe3+, and Co2+ ions. PET process, coupled with the ICT process, is proposed to explain the observed spectral response.
The sequence segment 181-200 of the Torpedo nicotinic acetylcholine receptor (nAChR) #alpha#subunit forms a binding site for #alpha#-bungarotoxin (#alpha#-BTX). Synthetic peptides corresponding to the homologous sequences of human, calf, mouse, chicken, frog, and cobra muscle nAChR #alpha#1 subunits were tested for their ability to bind "1"2"5I-#alpha#-BTX, and differences in #alpha#-BTX affinity were determined by using solution (IC_5_0s) and solid-phase (K_ds) assays. Panels of overlapping peptides corresponding to the complete #alpha#1 subunit of mouse and human were also tested for #alpha#-BTX binding, but other sequence segments forming the #alpha#-BTX site were not consistently detectable. The role of a putative vicinal disulfide bound between Cys-192 and -193, relative to the Torpedo sequence, was determined by modifying the peptides with sulfhydryl reagents. Reduction and alkylation of the peptides decreased ...
2-Azido[#alpha#-"3"2P]adenosine diphosphate (2-azido[#alpha#-"3"2P]ADP) has been used to photolabel the ADP/ATP carrier in beef heart mitochondria. In reversible binding assays carried out in the dark, this photoprobe was found to inhibit ADP/ATP transport in beef heart mitochondria and to bind to two types of specific sites of the ADP/ATP carrier characterized by high-affinity binding (K/sub d/ = 20 #mu#M) and low-affinity binding (K/sub d/ = 400 #mu#M). In contrast, it was unable to bind to specific carrier sites in inverted submitochondrial particles. Upon photoirradiation of beef heart mitochondria in the presence of 2-azido[#alpha#-"3"2P]ADP, the ADP/ATP carrier was covalently labeled. After purification, the photolabeled carrier protein was cleaved chemically by acidolysis or cyanogen bromide and enzymatically with the Staphylococcus aureus V8 protease. In the ADP/ATP carrier ...
An analogue of hGH isolated from plerocercoids of the tapeworm Spirometra mansonoides displaces ["1"2"5I]hGH from its receptors in rabbit, rat, and hamster liver membranes. Biologically, plerocercoid growth factor (PGF) is more similar to hGH than to other mammalian GH's but has not been shown to bond human cells. Receptors specific for hGH have been described on cultured human lymphocytes (IM-9). In this study, the authors compared the binding of PGF and hGH in IM-9 cells and in rabbit hepatic membranes. IM-9 lymphocytes (12 x 10"6 cells/tube) were incubated with ["1"2"5I]hGH and increasing concentrations of hGH (ng/ml) or PGF (serial dilutions) for 90 min at 30"0 C. Specific binding (B_0 - NSB) was determined for each dose of hGH or PGF and the binding curves were analyzed by logit-log regression. The results show that PGF displaced ["1"2"5I]hGH from human cells in a dose dependent manner (r = 0.98). Based on the IM-9 ...
Attention deficit hyperactivity disorder (ADHD) has been known as psychiatric disorder in childhood associated with dopamine dysregulation. In present study, we investigated changes in dopamine transporter (DAT) density of the basal ganglias using I-123 N-(3-iodopropen-2-yl) -2-carbomethoxy-3beta-(4-chlorphenyl) tropane (I-123 IPT) SPECT in children with ADHD before and after methylphenidate treatment. Nine drug-naive children with ADHD and seven normal children were included in the study. We performed brain SPECT two hours after the intravenous administration of I-123 IPT and made both quantitative and qualitative analyses using the obtained SPECT data, which were reconstructed for the assessment of specific/nonspecific DAT binding ratios in the basal ganglia. All children with ADHD reperformed (123I)IPT SPECT after treatment with methylphenidate (0.7mg/kg/d) during about 8 weeks. SPECT data reconstructed for the assessment of specific/nonspecific DAT ...
The general principles of Cu(II) binding to algal waste from agar extraction, composite material and algae Gelidium, and different modelling approaches, are discussed. FTIR analyses provided a detailed description of the possible binding groups present in the biosorbents, as carboxylic groups (D-glucuronic and pyruvic acids), hydroxyl groups (cellulose, agar and floridean starch) and sulfonate groups (sulphated galactans). Potentiometric acid-base titrations showed a heterogeneous distribution of two major binding groups, carboxyl and hydroxyl, following the quasi-Gaussian affinity constant distribution suggested by Sips, which permitted to estimate the maximum amount of acid functional groups (0.36, 0.25 and 0.1 mmol g{sup -1}) and proton binding parameters (pK{sup '}{sub H}=5.0,5.3and4.4;m{sub H} = 0.43, 0.37, 0.33), respectively for algae Gelidium, algal waste and composite material. A ...
Involvement of the dopaminergic system has been suggested in patients suffering from attention deficit hyperactivity disorder (ADHD) since the symptoms can be successfully treated with methylphenidate, a potent blocker of the dopamine transporter (DAT). This study reports the findings on the status of the DAT in adults with ADHD before and after commencement of treatment with methylphenidate, as measured using [{sup 99m}Tc]TRODAT-1. Seventeen patients (seven males, ten females, aged 21-64 years, mean 38 years) were examined before and after the initiation of methylphenidate treatment (3 x 5 mg/day). All subjects were injected with 800 MBq [{sup 99m}Tc]TRODAT-1 and imaged 3 h p.i. Single-photon emission tomography (SPET) scans were acquired using a triple-headed gamma camera. For semi-quantitative evaluation of the DAT, transverse slices corrected for attenuation were used to calculate specific binding in the striatum, with the cerebellum used as background ...
Extending the usual endpoint and midpoint interactions, we introduce numerous kinds of interactions, labelled by a parameter lambda and obtain a non-commutative and associative string field algebra by adding up all interactions. With this algebra we develop a covariant open bosonic string field theory, which reduces to Witten's open bosonic string field theory under a special string length choice.
The nature of interaction of some boromagnesium minerals with water is studied, the main stages of interaction are established. The methods of thermo-gravimetric, X-ray phase and chemical analyses are applied to state intermediate and final phases of magnesium borate interaction with water. ''Preobrazhenskite'' - ''inderite'' paragenesis is established. The notion ''magnesium borate solubility'' is shown to be senseless.
We present our plans for a Monte-Carlo code simulating all possible combinations of (electromagnetic) interactions between colliding electron, positron, and both high-energy and laser photon beams, based on the ABEL code for beam-beam interaction. The implementation and first results for the laser-e{sup -} interaction are described. ((orig.)).
We present our plans for a Monte-Carlo code simulating all possible combinations of (electromagnetic) interactions between colliding electron, positron, and both high-energy and laser photon beams, based, on the ABEL code for beam-beam interaction. The implementation and first results for the laser-e"- interaction are described.
Off-shell interactions for localized closed-string tachyons in C/Z{sub N} superstring backgrounds are analyzed and a conjecture for the effective height of the tachyon potential is elaborated. At large N, some of the relevant tachyons are nearly massless and their interactions can be deduced from the S-matrix. The cubic interactions between these tachyons and the massless fields are computed in a closed form using orbifold CFT techniques. The cubic interaction between nearly-massless tachyons with different charges is shown to vanish and thus condensation of one tachyon does not source the others. It is shown that to leading order in N, the quartic contact interaction vanishes and the massless exchanges completely account for the four point scattering amplitude. This indicates that it is necessary to go beyond quartic interactions or to include other fields to ...
Off-shell interactions for localized closed-string tachyons in C/Z{sub N} superstring backgrounds are analyzed and a conjecture for the effective height of the tachyon potential is elaborated. At large N, some of the relevant tachyons are nearly massless and their interactions can be deduced from the S-matrix. The cubic interactions between these tachyons and the massless fields are computed in a closed form using orbifold CFT techniques. The cubic interaction between nearly-massless tachyons with different charges is shown to vanish and thus condensation of one tachyon does not source the others. It is shown that to leading order in N, the quartic contact interaction vanishes and the massless exchanges completely account for the four point scattering amplitude. This indicates that it is necessary to go beyond quartic interactions or to include other fields to ...
Event generators that handle neutrino-nucleon interaction have been developed for the FLUKA code [1]. In earlier FLUKA versions only quasi-elastic (QEL) interactions were included, and the code relied on external event generators for the resonance (RES) and deep inelastic scattering (DIS). The new DIS+RES event generator is fully integrated in FLUKA and uses the same hadronization routines as those used for simulating hadron-nucleon interactions. Nuclear effects in neutrino-nucleus interactions are simulated within the same framework as in the FLUKA hadron-nucleus interaction model (PEANUT), thus profiting from its detailed physics modelling and longstanding benchmarking. The generators are available in the standard FLUKA distribution. They are presently under development and several improvements are planned to be implemented. The physics relevant to the neutrino-nucleon ...
This study reports on the physical-chemical behaviour of swelling di-octahedral clays (smectites) and their interaction with aqueous solutions and bacteria (Shewanella putrefaciens). Experimental results are presented for compacted clays, hydrated under confined volume conditions, using a new type of reaction-cell (the 'wet-cell' of Warr and Hoffman, 2004) that was designed for in situ X-ray diffraction (XRD) measurement. For comparison, dispersed clay systems were studied using standard batch solutions subjected to varying degrees of agitation. The combination of time-dependent in situ XRD measurements with gravimetric measurements and calculated diffraction patterns using the CALCMIX software (Plancon and Drits, 1999) allowed to successful quantification of the dynamics of water uptake and storage. This analytical procedure combined with published water vapour adsorption data enabled determination of the abundance of structured water layers, ...
We have previously shown that avian reovirus (ARV) #sigma#A and #sigma#NS proteins possess dsRNA and ssRNA binding activity and suggested that there are two epitopes on #sigma#A (I and II) and three epitopes (A, B, and C) on #sigma#NS. To further define the location of epitopes on #sigma#A and #sigma#NS proteins and to further elucidate the biological functions of these epitopes by using monoclonal antibodies (MAbs) 62, 1F9, H1E1, and 4A123 against the ARV S1133 strain, the full-length and deletion fragments of S2 and S4 genes of ARV generated by polymerase chain reaction (PCR) were cloned into pET32 expression vectors and the fusion proteins were overexpressed in Escherichia coli BL21 strain. Epitope mapping using MAbs and E. coli-expressed deletion fragments of #sigma#A and #sigma#NS of the ARV S1133 strain, synthetic peptides, and the cross reactivity of MAbs to heterologous ARV strains demonstrated that epitope II on #sigma#A was located at amino acid residues ...
Multimodal interfaces are becoming increasingly ubiquitous with the advent of mobile devices, accessibility considerations, and novel software technologies that combine diverse interaction media. In addition to improving access and delivery capabilities, such interfaces enable flexible and personalized dialogs with websites, much like a conversation between humans. In this paper, we present a software framework for multimodal web interaction management that supports mixed-initiative dialogs between users and websites. A mixed-initiative dialog is one where the user and the website take turns changing the flow of interaction. The framework supports the functional specification and realization of such dialogs using staging transformations -- a theory for representing and reasoning about dialogs based on partial input. It supports multiple interaction interfaces, and offers sessioning, caching, and ...
We study the characteristics of cyclotron wave-particle interaction in a typical hydrogen plasma. The numerical calculations of minimum resonant energy Emin, resonant wave frequency ?, and pitch angle diffusion coefficient D?? for interactions between R-mode/L-mode and electrons/protons are presented. It is found that Emin decreases with ? for R-mode/electron, L-mode/proton and L-mode/electron interactions, but increase with ? for R-mode/proton interaction. It is shown that both R-mode and L-mode waves can efficiently scatter energetic (10 keV-100 keV) electrons and protons and cause precipitation loss at L=4, indicating that perhaps wave-particle interaction is a serious candidate for the ring current decay. (authors)
Three regio-isomers of N-(N-benzylpiperidin-4-yl)-4-iodobenzamide, IBP, were prepared and evaluated for their sigma affinities. All three isomers (2, 3, and 4-substituted) showed high affinities for sigma-1 receptors in guinea pig brain membranes (Ki - 1.64 nM, 3.02 nM, 1.70 nM respectively) against ["3H]-(+)-pentazocine, a sigma-1 selective ligand. 2-IBP and 4-IBP showed modest affinities for sigma-2 sites in rat liver (Ki = 29.6 nM. 25.2 nM respectively) against ["3H]DTG in the presence of dextrallorphan to mask sigma-1 sites. The homologous competition binding studies of 4-["1"2"5I]BP in MCF-7 human breast tumor cells showed high affinity dose-dependent binding. Competition binding studies with haloperidol and DTG also showed a high affinity binding (Ki = 4.6 nM, 60 nM respectively), demonstrating the sigma specificity. The saturation binding (Scatchard analysis) of ["3H]DTG with ...
Administration of [ring-U-14C]propanil (3,4-dichloropropionanilide) to male Sprague-Dawley rats (30, 100, and 300 mg/kg, ip) increased the formation of methemoglobin at the two highest doses. Following a propanil dose of 100 mg/kg, methemoglobin formation attained a maximum level of 5% by 1.5 hr and declined to normal levels (approximately 2.5%) by 12 hr. Hemoglobin binding attained a maximum level of 50 pmol/mg protein by 12 hr, and remained constant for 24 hr. Following a propanil dose of 300 mg/kg, methemoglobin formation attained a maximum level of 24% by 4.5 hr, and declined to a level of 5% by 24 hr. Hemoglobin binding attained a maximum level of 425 pmol/mg protein by 12 hr, and remained constant for 24 hr. Hemoglobin binding was also detected at the lowest propanil dose (10 pmol/mg protein) even though methemoglobin formation was not observed. HPLC analysis of alkaline-treated hemoglobin from propanil-treated rats ...
Platelets from dogs with Basset Hound Hereditary Thrombopathy (BHT) display a thrombasthenia-like aggregation defect but have been shown to have normal amounts of platelet membrane glycoproteins IIb and IIIa (GP IIb-IIIa). In order to investigate the possibility of a functionally abnormal GPIIb-IIIa complex, which might be unable to bind fibrinogen after stimulation, fibrinogen binding in BHT was evaluated. Two canine fibrinogen preparations were used, one from BHT dogs and one from normal control dogs, as well as a human fibrinogen preparation. Platelets from BHT and normal dogs were activated with 1 x 10/sup -5/M ADP in the presence of /sup 125/I-labeled fibrinogen and the surface bound radioactivity quantitated. For all fibrinogen preparations, the amount of fibrinogen bound by BHT platelets was not significantly different than that bound by normal dog platelets. BHT platelets bound 23,972 +/- 3612 and normal dog platelets bound 23,033 +/- ...
Positron Emission Tomography (PET) was used to analyze in vivo antagonist binding to human myocardial muscarinic cholinergic receptor. The methiodide salt of the muscarinic antagonist, quinuclidinyl benzilate (MQNB), was labeled with the positron emitter, Carbon-11, and injected intravenously to 8 normal subjects. /sup 11/C-MQNB concentration was determined in vivo in the ventricular septum from 40 cross-sectional images acquired at the same transverse level over a period of 70 minutes. In 4 subjects, various amounts of unlabeled atropine were rapidly injected at 20 minutes to study whether atropine competitively inhibited MQNB. The kinetics of binding of /sup 11/C-MQNB were not the same in vivo and in vitro. The apparent dissociation rate of /sup 11/C-MQNB in vivo was much slower (by 1 to 2 orders of magnitude) than that observed in vitro with /sup 3/H-QNB. After atropine injection, /sup 11/C-MQNB dissociated from its ...
Culex mosquitoes introduce the pathogens responsible for filariasis, West Nile virus, St. Louis encephalitis, and other diseases into humans. Currently, traps baited with oviposition semiochemicals play an important role in detection efforts and could provide an environmentally friendly approach to controlling their populations. The odorant binding proteins (OBPs) in the female's antenna play a crucial, if yet imperfectly understood, role in sensing oviposition cues. Here, we report the X-ray crystallography and NMR 3D structures of OBP1 for Culex quinquefasciatus (CquiOBP1) bound to an oviposition pheromone (5R,6S)-6-acetoxy-5-hexadecanolide (MOP). In both studies, CquiOBP1 had the same overall six-helix structure seen in other insect OBPs, but a detailed analysis revealed an important previously undescribed feature. There are two models for OBP-mediated signal transduction: (i) direct release of the pheromone from an internal binding ...
The DNA sequence motif ATTTGCAT (octamer) or its inverse complement has been identified as an evolutionarily conserved element in the promoter region of immunoglobulin genes. Two major DNA-binding proteins that bind in a sequence-specific manner to the octamer DNA sequence have been identified in mammalian species--a ubiquitously expressed protein (Oct-1) and a lymphoid-specific protein (Oct-2). During characterization of the promoter region of the chicken immunoglobulin light chain gene, the authors identified two homologous octamer-binding proteins in chicken B cells. when the cloning of the human gene for Oct-2 revealed it to be a member of a distinct family of homeobox genes, they sought to determine if the human Oct-2 cDNA could be used to identify homologous chicken homeobox genes. Using a human Oct-2 homeobox-specific DNA probe, they were able to identify 6-10 homeobox-containing genes in the chicken genome, ...
ATR-X (alpha-thalassemia/mental retardation, X-linked) syndrome is a human congenital disorder that causes severe intellectual disabilities. Mutations in the ATRX gene, which encodes an ATP-dependent chromatin-remodeler, are responsible for the syndrome. Approximately 50% of the missense mutations in affected persons are clustered in a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, ADD{sub ATRX}), whose function has remained elusive. Here we identify ADD{sub ATRX} as a previously unknown histone H3-binding module, whose binding is promoted by lysine 9 trimethylation (H3K9me3) but inhibited by lysine 4 trimethylation (H3K4me3). The cocrystal structure of ADD{sub ATRX} bound to H3{sub 1-15}K9me3 peptide reveals an atypical composite H3K9me3-binding pocket, which is distinct from the conventional trimethyllysine-binding aromatic cage. Notably, H3K9me3-pocket mutants and ATR-X syndrome mutants are ...
We analyse how the structure of the inner curst is influenced by the pairing correlations. The inner-crust matter, formed by nuclear clusters immersed in a superfluid neutron gas and ultra-relativistic electrons, is treated in the Wigner-Seitz approximation. The properties of the Wigner-Seitz cells, i.e., their neutron to proton ratio and their radius at a given baryonic density, are obtained from the energy minimization at beta equilibrium. To obtain the binding energy of baryonic matter we perform Skyrme-HFB calculations with zero-range density-dependent pairing forces of various intensities. We find that the Wigner-Seitz cells have much smaller numbers of protons compared to previous calculations. For the dense cells the binding energy of the configurations with small proton numbers do not converge to a well-defined minimum value which precludes the determination of their structure. We show that for these cells there is a significant ...
Somatogenic hormones play an important role in regulation of receptors for prolactin (PRL) and estrogen. Plerocercoids of the tapeworm, S. mansonoides produce a factor which mimics some, but not all of the actions reported for GH. Intact female rats were subjected to a constant infusion of plerocercoid growth factor (PGF) via a subcutaneous infection for two weeks to determine if PGF influences receptors for PRL, GH or estradiol. The rate of weight gain in the PGF-treated rats was accelerated in spite of a marked reduction in serum GH. Partially-purified PGF specifically displaced [125I]hGH from rat liver receptors but microsomes prepared from rats treated with PGF specifically bound significantly less [125I]hGH than microsomes from control rats. The reduction in [125I]hGH binding was not due to occupancy or to a change in affinity but to a suppression in receptor concentration. Scatchard analysis of [3H]estradiol binding in rat liver cytosols ...
A class-V myosin, myosin V, one of 18 known classes of actin-based motor proteins, plays a role in transporting organelles within a cell. Unlike myosin-II, which functions as an assembly in the thick filaments of muscle, myosin V is a two-headed processive motor protein, which functions as a single molecule: myosin V performs many consecutive steps before it detaches from an actin filament accompanied by catalytic cycles of ATP (adenosine 5'-triphosphate) ase. The mechanism of such chemomechanical steps is explained by a 'Hand-over-hand model' in which two heads of myosin V alternately repeat single-headed and double-headed bindings with an actin filament. To investigate the binding state of myosin V at several key nucleotide states during ATP hydrolysis, we measured the mechanical properties of a single myosin V - actin complex by applying an external load with optical trap.
The effects of muscarinic agonists and diisopropylfluorophosphate (DFP) on muscarinic receptor density and muscarinic receptor-mediated responses was assessed in mouse brain and mouse neuroblastoma cells (clone N1E-115). Utilizing the antagonist ({sup 3}H)quinuclidinyl benzilate (({sup 3}H)QNB), there was no difference in the maximal binding capacity (B{sub max}) or equilibrium dissociation constant (K{sub d}) between untreated and 24 hour DFP-treated mice. However, one administration of DFP produced a 24% and 33% decrease in B{sub max} measured by ({sup 3}H)N-methylscopolamine (({sup 3}H)NMS) after 18 and 24 hours which was rapidly reversible within 36 hours after DFP treatment. The loss of ({sup 3}H)NMS binding sites following acute DFP treatment was not accompanied by a change in a particular muscarinic receptor binding conformation. Furthermore, the magnitude of muscarinic receptor-mediated phosphoinositide hydrolysis ...
The Thomsen-Friedenreich (T) antigen, #betta#-D-Gal-(1->3)-#alpha#-D-GalNAc, is exposed in reactive form on many human adenocarcinomata, but not on corresponding benign tissues. Peanut lectin (PNA) has a strong binding affinity for the T antigen and reportedly binds preferentially to certain malignant tissues. We investigated the potential of radio-labelled PNA as a tumour localising agent in an animal model system using a mouse lymphoma (RI) shown to bind fluorescein-labelled PNA in vitro. The radio-iodinated lectin showed good tumour localisation and rapid blood clearance. Clear images of tumours were obtained, in serial scintigraphic imaging, by 24 and 48 h. No blood background subtraction was necessary. Biodistribution studies revealed tumour to blood ratios in mice were 6:1 (at 24 h) and 17:1 (at 48 h), and tumour to muscle ratios were 34:1 (at 24 h) and 40:1 (at 48 h). Rapid in vivo breakdown of _1_2_5I-PNA led to ...
Two headed motor proteins, such as kinesin and dynein, hidrolyze environmental ATP in order to propel unidirectionally along cytoskeletal filaments such as microtubules. In the case of kinesin, protein heads bind primarily on the alpha tubulin site of asymmetric alpha-beta 8nm-long tubulin dimers that constitute the microtubular protofilaments. Kinesin dimers overcome local binding forces up to 5pN and are known to move on protofilaments with ATP concentration-dependent speeds while hydrolizing on average one ATP molecule per 8nm step. The salient features of protein trajectories are the distinct abrupt usually 8nm-long steps from one tubulin dimer to the next interlaced with long quiescent binding periods at a tubulin site. Discrete walks of this type are characterized by substantially reduced variances compared to pure biased random walks, and as a result rule out flashing-type ratchet models as possible mechanisms for ...
This progress report covers period from Nov. 1, 1989 to Aug. 31, 1990. The long term objective was to develop receptor-binding radiotracers for SPECT or PET imaging of CNS or peripheral nervous system. The specific chemistry aims, as understood on the basis of past findings, were: to synthesize and develop a more polar analogs of 4IQNB, possessing similar binding characteristics but eliminated more rapidly from the surrounding tissues and the target organ, to design a method of introducing a technetium chelating group onto a molecule or cholinergic agent without drastic lowering of its apparent affinity, to synthesize and develop radiotracers based on m-AChR antagonists selective for one of the subtypes of the receptor. The chemistry service aims were to prepare and characterize (R,R)- and (R,S)-4IQNB and derivatives, to provide the triazene intermediate to other investigators, and to provide ({sup 123}I)4IQNB for in vivo imaging. The ...
Modification of DNA and double-stranded deoxyoligonucleotides with antitumor 1,2-diamino-cyclohexanedinitroplatinum(II) (Pt-dach) complexes was investigated with the aid of physico-chemical methods and chemical probes of nucleic acid conformation. The three Pt-dach complexes were used which differed in isomeric forms of the dach non-leaving ligand-Pt(1R,2R-dach), Pt(1S,2S-dach) and Pt(1R,2S-dach) complexes. The latter complex has lower antitumor activity than the other two Pt-dach complexes. Pt(1R,2S-dach) complex exhibits the slowest kinetics of its binding to DNA and of the conversion of monofunctional binding to bifunctional lesions. The anomalously slow electrophoretic mobility of multimers of the platinated and ligated oligomers suggests that bifunctional binding of Pt-dach complexes to a d(GG) site within double-stranded oligonucleotides induces bending of the oligomer. It is proposed that different effects of the ...
The production of molecularly imprinted polymers (MIPs) for the recognition of C-terminal cholecystokinin pentapeptide (CCK-5) in the presence of metal ion is reported. The MIPs were produced under the same molar ratio of template to monomers (acrylamide, N,N'-methylene bisacrylamide) in the presence or absence of nitrilotriacetic acid-nickel (Ni-NTA) complex. Scanning electron microscopy images of MIPs were obtained in an attempt to correlate the adsorption characteristics with polymer's morphology. Subsequently Ni2+ was removed and substituted by other divalent ions such as Mg2+, Fe2+, Zn2+, Co2+ and Cu2+. It was found that polymers containing the metal ion complex with the order Fe-NTA, Ni-NTA and Cu-NTA presented lower dissociation constant values than the rest thus exhibiting stronger guest binding activity. The percentage of theoretical maximum binding sites Bmax was almost the same for these ions, indicating that the ion-template ...
Synthetic oligoribonucleotides have been used to probe the interaction of MS2 coat protein with the translational operator of the MS2 replicase gene. We have investigated the possible formation of a...Full Text Available
In addition to the well documented role of cytokines in mediating tissue-level interactions, it is now clear that matrix macromolecules fulfil a complementary regulatory function. Data highlighted in...Full Text Available
The interactions between biochemical processes and mechanical signaling play important roles during various cellular processes such as wound healing, embryogenesis, metastasis, and cell migration. While...Full Text Available
Interactions between presynaptic and postsynaptic cellular adhesion molecules (CAMs) drive synapse maturation during development. These trans-synaptic interactions are regulated by alternative splicing...Full Text Available
A major goal in perceptual neuroscience is to understand how signals from different sensory modalities are combined to produce stable and coherent representations. We previously investigated interactions...Full Text Available
We describe the interactions of two benzimidazole derivatives, astemizole (AST) and lansoprazole (LNS), with anomalous aggregates of tau protein (neurofibrillary tangles). Interestingly, these...Full Text Available
Phenazines are redox-active small molecules that play significant roles in the interactions between pseudomonads and diverse eukaryotes, including fungi. When Pseudomonas aeruginosa...Full Text Available
OBJECTIVES:To investigate the prevalence of potential drug interactions at the intensive care unit of a university hospital in Brazil and to analyze their clinical significance.METHODS:This...Full Text Available
The Salmonella PmrA-PmrB system controls the expression of genes necessary for polymyxin B resistance. Four loci were previously identified as part of the regulon, and interaction of...Full Text Available
Analytical method of theoretical simulation of collective hydrodynamic instabilities of intensive flows of discrete radiators, interacting with each other only through the coherent fields of their spontaneous radiation in corresponding media was suggested...
BackgroundGenetic interactions within hybrids influence their overall fitness. Understanding the details of these interactions can improve our understanding of speciation. One experimental...Full Text Available
1. Interactions of pyrazole and ethanol were studied in three laboratory test procedures. They included sleeping time in mice, rotor rod balance in rats and lever pressing behaviour of rats. 2....Full Text Available
External application of auxin and cytokinin is required for the formation of flower buds on thin-layer tissue explants of Nicotiana tabacum cv Samsun. Interaction between both plant...Full Text Available
Understanding the interactions between herpesviruses and their host cells and also the interactions between neoplastically transformed cells and the host immune system is fundamental to understanding...Full Text Available
The C1 fixation test is widely used for the study of the interaction between immunoglobulins, their fragments and the complement system. Some factors influencing the apparent extent of the C1 fixation...Full Text Available
We analyze transport through conical channels due to the difference in particle concentration on the two sides of the membrane. Because of the detailed balance, fluxes of non-interacting particles...Full Text Available
A pedagogical introduction to the equivalence theorem for longitudinal vector bosons in electroweak theories is given and the problem of tree-level unitarity at high energies in models of electroweak interactions is briefly reviewed. To make the treatment self-containded, the basic of the Standard Model are summarized in an appendix.
Magnetotactic bacteria contain chains of magnetically interacting crystals (magnetosome crystals), which they use for navigation (magnetotaxis). To improve magnetotaxis efficiency, the magnetosome crystals...Full Text Available
Detectors for a photon-photon collider are envisaged using as guide-lines the physics goals and the interaction point environment. Production of SUSY Higgs scalar and pseudo-scalar is emphasized. Some aspects of the interaction point environment are discussed. ((orig.)).
General balance laws and constitutive relations are developed for convective hydrothermal geothermal reservoirs. A fully interacting rock-fluid system is considered; typical rock-fluid interactions involve momentum and energy transfer, and the dependence ...
BackgroundPolyethyleneimine (PEI), which can interact with negatively charged DNA through electrostatic interaction to form nanocomplexes, has been widely attempted to use as a gene...Full Text Available
Zipper-interacting protein kinase (ZIPK) is a member of the death-associated protein kinase family associated with apoptosis in nonmuscle cells where it phosphorylates myosin regulatory light chain...Full Text Available
BackgroundBrains interact with the world through actions that are implemented by sensory and motor processes. A substantial part of these interactions consists in synchronized goal-directed...Full Text Available
The extracellular domain of human fibroblast growth factor receptor (XC-FGF-R) was expressed in Escherichia coli. The protein was purified to homogeneity and the interaction with basic fibroblast growth...Full Text Available
The carboxyl-terminal region of tubulin alpha and beta subunits plays a major role in regulating its assembly into microtubules and constitutes an essential domain for the selective interaction of microtubule-associated...Full Text Available
Oligopeptidic drugs such as β-lactams and angiotensin-converting enzyme inhibitors share the same carriers in humans and animals, which results in possible pharmacokinetic interactions. To model...Full Text Available
Algebraic properties of the analytical model, describing electro-magnetic weak interaction with the two-level system with two-fold degenerate state are considered. The expressions for the coherent states and Green function of the system are obtained.
We proposed a faster pedigree-based generalized multifactor dimensionality reduction algorithm, called PedG-MDR II (PII), to detect gene-gene interactions underlying complex traits. Inherited...Full Text Available
Risoe`s 40th anniversary was celebrated June 3, 1998 by a symposium held at Risoe. The interaction of research at Risoe with academia and industry was presented in both national and international perspective. Most of the presentations are in English, a few in Danish. (au)
The adsorption interaction of different types of demulsifiers and the oils of Western Siberia is covered. The high adsorption capacity of Separol-5084 and disolvan-4490 reagents is established. The positive role of this phenomen in breaking aqueous oil emulsifiers is theoretically substantiated and experimentally confined.
... interactive surfaces and interfaces, and 3) the more complex a ... carbonate or calcium phosphate with a thin interface ... diameter) for nerve prosthesis. ...
We construct a phenomenological model which describes the dynamical chiral symmetry breaking (DCSB) of a QCD vacuum and reproduces meson spectra. Quark condensates, the pion decay constant, and meson spectra are well reproduced by the phenomenological interaction which consists of a linear confining potential, a Coulombic potential, and the close-quote t Hooft determinant interaction. In this model, the close-quote t Hooft determinant interaction plays an important role to not only the mass difference between the #eta# and #eta#"' mesons, but other meson masses through DCSB. copyright 1997 The American Physical Society.
Information Technology Glossary of Terms. Applets: Programs that run inside net browsers, usually in Java and typically involving modestly interactive ...
The results of finite element calculations detailing the interactions of eddy currents with fine collinear slots in nonferromagnetic and ferromagnetic conductors are presented. These are applicable to both remote field eddy current inspection tools and conventional reflected impedance eddy current probes. The calculations show that, while fine slots have little interaction with collinear induced currents in nonferromagnetic conductors, there are much larger effects in ferromagnetic conductors. This is due to magnetic field interactions. The term eddy current inspection' is therefore somewhat restrictive and the much broader term electromagnetic inspection' is proposed.
Inelastically scattered neutron spectra and angular distributions measured for a number of nuclei at the 9.1 and 14.4 MeV incident neutron energies are fitted well as a sum of neutron evaporation spectrum and the direct interaction part. For the last one the practical scheme of parametrization based on direct interaction theory is presented. The relative contribution of direct interactions in double differential cross sections and parameters of neutron evaporation spectra have been evaluated. All results have a simple physical interpretation and may be useful at interpolating of data in a wide energy interval.
Properties of unique parity states in odd-proton (/sub 77/Ir, /sub 79/Au) and odd-neutron nuclei (/sub 78/Pt) are investigated in the framework of the interacting boson-fermion approximation model. The core (boson)-particle (fermion) interaction is represented by a quadrupole-quadrupole interaction and an exchange term, which takes into account the effects of the Pauli exclusion principle. The even-even core nucleus is described in terms of the IBA-1 hamiltonian. The change in the properties of the corresponding odd-A nuclei can be interpreted in terms of a transition of the core hamiltonian between the O(6) and SU(3) limiting cases.
Properties of unique parity states in odd-proton (_7_7Ir, _7_9Au) and odd-neutron nuclei (_7_8Pt) are investigated in the framework of the interacting boson-fermion approximation model. The core (boson)-particle (fermion) interaction is represented by a quadrupole-quadrupole interaction and an exchange term, which takes into account the effects of the Pauli exclusion principle. The even-even core nucleus is described in terms of the IBA-1 hamiltonian. The change in the properties of the corresponding odd-A nuclei can be interpreted in terms of a transition of the core hamiltonian between the O(6) and SU(3) limiting cases. (orig.).
... Propulsive efficiency is equivalent to the product of thrust efficiency and the hull/waterjet interaction efficiency. ... t'waterjet pump Ktorque repeated ...
Abstract. The potential effects of synthetic unmethylated oligodeoxynucleotides (ODN) containing CpG motifs, mimicking bacterial DNA, has never been evaluated on the immune response in the teleost fish gilthead seabream (Sparus aurata), the most important fish species in Mediterranean aquaculture. First, binding and competition studies have demonstrated that binding is saturated and promiscuous, suggesting the participation of several receptors. Moreover, leucocyte cytotoxic (NCC) activity, production of ROIs (reactive oxygen intermediates), and expression of immune-relevant genes was greatly primed by ODNs. Focusing on the mechanism, the TLR9 gene is widely distributed in seabream tissues and differently regulated in vitro by several stimuli. Moreover, and for the first time in fish, TLR9...
Homidium bromide and isometamidium chloride are used extensively in the treatment of bovine trypanosomiasis in Africa, but no specific and sensitive method to detect the drug in plasma has been published yet. Comparing the methods of other investigators it was found that they could not overcome the protein binding of these drugs which reduced the available and determined drug to 10% of the real concentrations. These techniques overcome the protein binding by enzyme digestion and an alteration of the pH before adding the sample directly on clean-up columns. Drug recover rates above 80% were obtained. For the detection, the HPLC was employed using a C18 reversed phase analytical column and UV detection, determining both drugs as intact molecules. (author).
Eight selected sulfonamide drugs were investigated as inhibitors of heat shock protein 90 (Hsp90). The investigation included simulated docking experiments to fit the selected compounds within the binding pocket of Hsp90. The selected molecules were found to readily fit within the ATP-binding pocket of Hsp90 in low-energy poses. The sulfonamides torsemide, sulfathiazole, and sulfadiazine were found to inhibit the ATPase activity of Hsp90 with IC50 values of 1.0, 2.6, and 1.5 mM, respectively. Our results suggest that these well-established sulfonamides can be good leads for subsequent optimization into potent Hsp90 inhibitors.
The dogmatic and constitutional basis as well as points of definition concerning the Technical Code Clean Air (TA Luft) are explained at first, followed by an assessment of the air pollution concentrations within the overall complex of the air pollution abatement measures, and an analyses of air pollution concentrations as a concretization of the state-of-the-art. In connection with the differentiation of the various applicability levels of TA Luft, the inhouse validy for authorities, the importance for law courts and, finally, the external binding effect for plant operators and possible third parties are discussed. At the center of attention are questions concerning validity claims and validity possibilities. (HSCH).
Since the elucidation of the structure of double helical DNA, the construction of small molecules that recognize and react at specific DNA sites has been an area of considerable interest. In particular, the study of transition metal complexes that bind DNA with specificity has been a burgeoning field. This growth has been due in large part to the useful properties of metal complexes, which possess a wide array of photophysical properties and allow for the modular assembly of an ensemble of recognition elements. Here we review recent experiments in our laboratory aimed at the design and study of octahedral metal complexes that bind DNA non-covalently and target reactions to specific sites. Emphasis is placed both on the variety of methods employed to confer site-specificity and upon the many applications for these complexes. Particular attention is given to the family of complexes recently designed that target single base mismatches in duplex ...
Since the elucidation of the structure of double helical DNA, the construction of small molecules that recognize and react at specific DNA sites has been an area of considerable interest. In particular, the study of transition metal complexes that bind DNA with specificity has been a burgeoning field. This growth has been due in large part to the useful properties of metal complexes, which possess a wide array of photophysical attributes and allow for the modular assembly of an ensemble of recognition elements. Here we review recent experiments in our laboratory aimed at the design and study of octahedral metal complexes that bind DNA non-covalently and target reactions to specific sites. Emphasis is placed both on the variety of methods employed to confer site-specificity and upon the many applications for these complexes. Particular attention is given to the family of complexes recently designed that target single base mismatches in duplex ...
Objective. Preterm neonates are susceptible to infection due to a combination of sub-optimal immunity and increased exposure to invasive organisms. Invasive fungal infections are associated with significant morbidity and mortality among preterm infants cared for in the neonatal intensive care unit (NICU). Mannose-binding lectin (MBL) is a component of the innate immune system, which may be especially important in the neonatal setting. The objective of this study was to investigate the presence of any association between MBL gene polymorphism and nosocomial invasive fungal infection in preterm neonates. Methods. Codon 54 (B allele) polymorphism in exon 1 of the MBL gene was investigated in 31 patients diagnosed as nosocomial invasive fungal infection and 30 control preterm neonates. Results...
Organic/metal interface properties are of high interest for the application of molecular (sub)monolayers to modify surface properties. They are applied for, e.g., molecular electronics, chemical sensing, or the tuning of injection barriers in organic electronic devices. We present a joint theoretical and experimental study of F{sub 4}TCNQ adsorbed on Cu(111). The electronic and structural properties were determined by ultraviolet photoelectron spectroscopy (UPS) and X-ray standing wave (XSW) measurements. To better understand the complex process of binding, we modelled the system using density-functional theory. We find forward-donation from the lone pairs of the molecule into metallic states and back-donation from the metal into the LUMO of the molecule. The data on Cu(111) are compared to F4TCNQ on Au(111) and Ag(111) as well as to investigations of pyrenetetraone on various coinage metals.
Evolutionary conservation of DNA sequences provides a tool for the identification of functional elements in genomes. We have created a database of evolutionary conserved regions (ECRs) in vertebrate genomes entitled ECRbase that is constructed from a collection of pairwise vertebrate genome alignments produced by the ECR Browser database. ECRbase features a database of syntenic blocks that recapitulate the evolution of rearrangements in vertebrates and a collection of promoters in all vertebrate genomes presented in the database. The database also contains a collection of annotated transcription factor binding sites (TFBS) in all ECRs and promoter elements. ECRbase currently includes human, rhesus macaque, dog, opossum, rat, mouse, chicken, frog, zebrafish, and two pufferfish genomes. It is freely accessible at http://ECRbase.dcode.org.
Conformationally constrained analogue synthesis was undertaken to aid in pharmacophore mapping and 3D-QSAR analysis of nitrobenzylmercaptopurine riboside (NBMPR) congeners as equilibriative nucleoside transporter 1 (ENT1) inhibitors. In our previous study [J. Med. Chem. 2003, 46, 831-837], novel regioisomeric nitro-1,2,3,4-tetrahydroisoquinoline conformationally constrained analogues of NBMPR were synthesized and evaluated as ENT1 ligands. 7-NO2-1,2,3,4-Tetrahydroisoquino-2-yl purine riboside was identified as the analogue with the nitro group in the best orientation at the NBMPR binding site of ENT1. In the present study, further conformational constraining was introduced by synthesizing 5prime-O,8-cyclo derivatives. The flow cytometrically determined binding affinities indicated that the...
The N{sub 1s} XPS band of pyridine chemisorbed on Al-ZSM-5 zeolite was found to be properly deconvoluted into three component peaks. In a previous contribution these three components were assigned to pyridine chemisorbed on two kinds of Bronsted acid sites and one Lewis acid site. This analysis is extended here to Fe-ZSM-5 and B-ZSM-5. Isomorphous substitution of Fe for Si or Al in the zeolite framework leads to a slight decrease in the binding energy of the N{sub 1s} Lewis component. In the case of B substitution a decrease in the binding energy of all three N{sub 1s} components is observed.
The thermal decrease of the order parameter can empirically be described by a single T{sup {epsilon}} power law with an exponent {epsilon} which depends on the dimensionality of the magnetic interactions and on whether the spin quantum number is integral or half-integral. We present experimental examples in which the order parameter shows a crossover between different T{sup {epsilon}} power laws as a function of temperature. This indicates that the magnetic interactions can change their dimensionality as a function of temperature. (orig.)
The properties of strange neutron stars have been studied with the use of the parameter sets stemming from the effective field theory. The impact of the strength of hyperon interactions on neutron star masses has been analyzed. The inclusion of additional nonlinear meson interaction terms together with the strong hyperon-hyperon interaction leads to the existence of additional stable stellar configurations. (authors)
Although silicosis has been studied extensively, the mechanism is still not fully understood. Experiments do provide evidence that the actions of unique properties of silica surface on the cell membrane are the starting point of silicotic processes. This paper summarizes literature on chemical properties of silica surface, and the effect of particle size on silica toxicity. This paper also discusses the ways in which silica dusts are though to interact with the cell membrane, with emphasis on freshness, hydrogen bonding, and free-radical interactions.
Peak at 60 deg in angular proton distribution in inelastic pion-carbon interactions is interpreted as generation of Cherenkov gluon radiation in flucton, passing into the shock wave with successive nucleus decay. Investigation of hadron-nuclear interactions with anomalous peak in angular proton distribution can be used as additional means for study both of flucton and mechanism of hadron-nuclear interactions. 5 refs.
The nuclear interaction probability of light charged particles in BaF[sub 2] crystals has been studied as a function of the incident particle energy. Light charged particles were identified in charge and mass by measuring their magnetic rigidity and their time-of-flight. The percentage of particles undergoing nuclear interactions has been measured for particles of charge from Z=1 to Z=6 and the experimental data are compared with the results of a model calculation. (orig.)
We report on large-scale applications of the ab initio, no-core shell model with the primary goal of achieving an accurate description of nuclear structure from the fundamental inter-nucleon interactions. In particular, we show that realistic two-nucleon interactions are inadequate to describe the low-lying structure of {sup 10}B, and that realistic three-nucleon interactions are essential.
The hyperfine interactions at the uranium site in the antiferromagnetic USb2 compound were calculated within the density functional theory (DFT) employing augmented plane wave plus local orbital (APW+lo) method. We investigated the dependence of the nuclear quadruple interaction to the magnetic structure in USb2 compound. The result shows that the 5f-electrons have the tendency to be hybridized with the conduction electrons.
Recent observations of the evolutionary properties of paired and interacting galaxies are reviewed, with special emphasis on their global emission properties and star formation rates. Data at several wavelengths provide strong confirmation of the hypothesis, proposed originally by Larson and Tinsley, that interactions trigger global bursts of star formation in galaxies. The nature and properties of the starbursts, and their overall role in galactic evolution are also discussed.
Interactions between spacecraft systems and the space charged particle environment are reviewed and recommendations are presented for both near-term and far-term research considerations. Transient environment models, large space structures, solar and nuclear power systems/environment interactions, single event upsets, material degradation, and planetary missions are addressed.
Interaction of drilling fluids with a geothermal reservoir formation can result in significant permeability impairment and therefore reduced well productivity. This interaction is studied under simulated in situ geothermal conditions of overburden stress, pore fluid pressure, temperature, and pore fluid chemistry. Permeability impairment of an East Mesa KGRA reservoir material is evaluated as a function of stagnation time, drilling fluid, and temperature. Results indicate that all of these parameters contribute significantly to the magnitude and the reversibility of the impairment.
We present an approach to automatically generate interfaces supporting personalized interaction with digital libraries; these interfaces augment the user-DL dialog by empowering the user to (optionally) supply out-of-turn information during an interaction, flatten or restructure the dialog, and enquire about dialog options. Interfaces generated using this approach for CITIDEL are described.
We have studied freshly prepared lysozyme solutions in heavy water for two NaCl concentrations as a function of temperature. Lysozyme solubilities in this solvent are determined by static light scattering. By small angle neutron scattering, we evidence that interactions between lysozyme molecules are characterized by a second virial coefficient A{sub 2} whether the solution is under-saturated or supersaturated. From the variation of A{sub 2} as a function of temperature we have evaluated the enthalpy corresponding to the interaction between lysozyme molecules. We show that the interactions between protein molecules are higher in heavy water than in light water. (authors). 13 refs., 3 figs.
Investigations of cadmium toxicity to microorganisms are now more concerned with the interactions of cadmium with different environmental factors and other metals. The interactions are complex and have not been thoroughly studied yet. Metal interactions may assume the form of synergism characterized by increase in toxicity, but also of antagonism in which one metal reduces the toxicity of another. Apart from cadmium interactions with such toxic metals as mercury and lead, interactions of cadmium with the essential trace elements seem to be very interesting because it has been assumed that algal cells take up cadmium by the system transporting these elements. A previous study showed that cadmium transport into Stichococcus bacillaris cells was inhibited by Mn/sup 2 +/ ions. Thus, it can be supported that there exist some possibilities of using those ions antagonistic to cadmium as ...
We investigate the effect of the intrinsic spin of a fundamental spinor field on the surrounding spacetime geometry. We show that despite the lack of a rotating stress-energy source (and despite claims to the contrary) the intrinsic spin of a spin-half fermion gives rise to a frame-dragging effect analogous to that of orbital angular momentum, even in Einstein-Hilbert gravity where torsion is constrained to be zero. This resolves a paradox regarding the counter-force needed to restore Newton's third law in the well known spin-orbit interaction. In addition, the frame-dragging effect gives rise to a {\\it long-range} gravitationally mediated spin-spin dipole interaction coupling the {\\it internal} spins of two sources. We argue that despite the weakness of the interaction, the spin-spin interaction will dominate over the ordinary inverse square Newtonian interaction in any process ...
This article reports research findings related to converging formats, media, practices, and ideas in the process of academics' interaction with electronic texts during a research project. The findings are part of the results of a study that explored interactions of scholars in literary and historical studies with electronic texts as primary materials. Electronic texts were perceived by the study participants as fluid entities because the electronic environment promotes seamless interactions with a variety of media and formats. Working with electronic texts combines some traditional information and research practices into new patterns of information behavior. The practice called "netchaining" combines aspects of networking with information-seeking practices to establish and shape online information chains, which link sources and people. Different forms of exploration of participants' research questions were enabled by ...
Experiments were carried out to learn methanol sorption characteristics of heat-treated coal. When Taiheiyo coal is heat-treated at 125{degree}C, performed with a first methanol adsorption at 25{degree}C, and then desorption at 25{degree}C, a site with strong interaction with methanol and a site with relatively weak interaction are generated in test samples. A small amount of methanol remains in both sites. Then, when the methanol is desorbed at as low temperature as 70{degree}C, the methanol in the site with strong interaction remains as it has existed therein, but the methanol in the site with relatively weak interaction desorbs partially, hence the adsorption amount in a second adsorption at 25{degree}C increases. However, when desorption is performed at as high temperature as 125{degree}C, the methanol in the site with strong interaction also desorbs, resulting in increased ...
The weak interaction between neutrons and protons has never been resolved experimentally. In analogy with the strong NN interaction, the weak NN interaction at low energy can be parametrized in terms of a meson exchange model with parity violating meson-nucleon couplings. Unlike the measured proton-proton weak interaction, the neutron-proton weak interaction is sensitive to the weak pion-nucleon coupling constant H{sub {pi}}{sup 1}. This coupling, which is responsible for the longest-ranged part of the weak NN interaction and is therefore an essential part of any description of weak interactions in nuclei, remains undetermined despite many years of effort. A measurement of the gamma ray directional asymmetry A{sub {gamma}} in the capture of polarized neutrons by parahydrogen has been proposed at Los Alamos National Laboratory. The goal of ...
For 12C 9Be interactions at a kinetic beam energy of 3.2 GeV per nucleon, the spectra of photons at laboratory angles in the range 55o-73o were measured off the kinematical region available to the interaction of single nucleons within colliding nuclei. The use of a fast trigger for selecting events involving the production of high-transverse-momentum photons made it possible to measure spectra off the kinematical boundary of four-nucleon interaction. It is shown that the proposed procedure is adequate to the problem of searches for and investigation of flucton-flucton interaction. In the kinematical region where flucton-flucton interaction can manifest itself, the cross sections in question are on the same order of magnitude as respective model predictions. In order to draw definitive conclusions on the role of flucton-flucton interaction, it is highly desirable ...
In drug development, Caco-2 cells are often employed to study the influence of membrane transporters on drug permeability. The aim of the current study was to characterize permeability and kinetic parameters of selected organic anionic compounds in Caco-2 cells, and to investigate whether the Caco-2 cell line may be used as an overall model to predict interactions on multiple membrane transporters in the intestine. Taurocholic acid (TCA) and estrone-3-sulfate (E(1) S) were used as model substrates. Possible inhibitors studied were TCA, E(1) S, taurolithocholic acid, fluvastatin, and glipizide. The effects of these compounds on initial uptake, apparent permeability, and intracellular end-point accumulations of the probe substrates were studied. Both interactions on apical and basolateral influx transporters were observed. These interactions were proposed to be mediated mainly by the apical sodium-dependent bile acid ...
We have isolated and sequenced cDNA clones encoding the human U1-70K snRNP protein, and have mapped this locus (U1AP1) to human chromosome 19. The gene produces two size classes of RNA, a major 1.7-kb...Full Text Available
The YTH (YT521-B homology) domain was identified by sequence comparison and is found in 174 different proteins expressed in eukaryotes. It is characterized by 14 invariant residues within an α-helix/β-sheet...Full Text Available
We have identified two novel, very closely related genes, SAS1 and SAS2, from Dictyostelium discoideum. These encode small, approximately 20-kilodaton proteins with amino acid sequences thought to be...Full Text Available
The Epstein-Barr virus protein, LMP1, is a functional mimic of the cellular receptor CD40, but signals to B lymphocytes in an amplified and sustained manner compared to CD40. LMP1 contributes...Full Text Available
We used fast absorbance spectroscopy to investigate in vivo binding dynamics and electron transfer between plastocyanin (pc) and photosystem I (PSI), and cytochrome (cyt) f...Full Text Available
The rate of appearance of labeled thyroxine (T4) and albumin in lymph from various areas after simultaneous i.v. injection of the labeled substances in conscious ambulatory sheep has been used to estimate...Full Text Available
(-)-N6-(R-4-Hydroxyphenylisopropyl)adenosine (HPIA) was iodinated with NaI and trace /sup 125/I. Mono- and diiodinated reaction products and the starting material were separated by high pressure liquid chromatography and the structures of the reaction products were verified by NMR. (-)-N6-(R-Phenylisopropyl)adenosine (PIA), IHPIA, and I2HPIA decreased rat atrial contractility with ED50 values of 24, 28, and 33 nM, respectively. The contractile effects of these compounds were competitively blocked by theophylline (KI . 7.9 microM), but were not affected by adenosine deaminase. IHPIA also inhibited (-)isoproterenol-stimulated cyclic AMP accumulation in adipocytes with an ED50 (10 nM) and to an extent (83%) nearly identical to PIA. (/sup 125/I)HPIA prepared using carrier-free /sup 125/I bound to adenosine receptors on membranes from rat cerebral cortex, adipocyte ghosts, and heart ventricles. Binding was inhibited stereospecifically by PIA and by other adenosine ...
CAP18 (an 18-kDa cationic antimicrobial protein) is a granulocyte-derived protein that can bind lipopolysaccharide (LPS) and inhibit various activities of LPS in vitro. The present study examined the...Full Text Available
The strength of adhesion of polybutylene terephthalate (PBT) on aluminium is investigated using density functional theory-based energy calculations. The aluminium atom is connected to a PBT monomer at different orientations, and total energies are calculated and compared to determine the most stable orientation. The binding is strongest when the Al is oriented at 180{sup 0} to the ester group of the monomer. Using this orientation as a basis, PBT adhesion on Ti, Ag, and Au is also investigated.
The docking protein p130Cas is a prominent Src substrate found in focal adhesions (FAs) and is implicated in regulating critical aspects of cell motility including FA disassembly and protrusion of the...Full Text Available
The natriuretic peptides are considered to be cardioprotective; however, their receptors have not been identified in human myocardium using radiolabeled analogs. Dendroaspis natriuretic peptide (DNP) has been recently identified as a new member of this peptide family and is thought to be less susceptible to enzymatic degradation. Therefore, we have developed the novel radiolabeled analog [125I]-DNP and used this to localize high-affinity (K(D)=0.2 nmol/L), saturable, specific binding sites in adult human heart (n=6) and coronary artery (n=8). In competition binding experiments, atrial natriuretic peptide and brain type natriuretic peptide had greater affinity for [125I]-DNP binding sites than C-type natriuretic peptide and the natriuretic peptide receptor (NPR)-C ligand, cANF. This rank order of potency suggested binding of [125I]-DNP was specific to NPR-A. Messenger RNA encoding NPR-A was identified in ...
Retinal pigment epithelial (RPE) cells, derived from the neuroectoderm, biosynthesize the novel lipid mediator neuroprotectin D1 (NPD1) from docosahexaenoic acid (DHA) in response to oxidative...Full Text Available
During protein synthesis, aminoacyl-tRNA (aa-tRNA) and release factors 1 and 2 (RF1 and RF2) have to bind at the catalytic center of the ribosome on the 50S subunit where they take part in peptide bond...Full Text Available
Maleic hydrazide (MH) is taken up by corn and pea seedling roots and bound to some material which is insoluble in 80% ethanol or 5% trichloroacetic acid. 14C-MH is stable metabolically; chromatography...Full Text Available
DescriptionIron deficiency anaemia is a common problem and may be particularly important to certain groups of vegetarians. This project investigates isolating and identifying iron-binding constituents of meat digests using human Caco-2 cell lines. Stable isotope techniques used to test whether one or more of these compounds enhance iron absorpion in vivo and could therefore be added to vegetarian products to imporve iron nutrition.
TH1 cytokine secretion was examined in response to synthetic peptides of the 85A component of the major secreted, fibronectin-binding antigen 85 complex from Mycobacterium tuberculosis in seven different...Full Text Available
Nop25 is a putative RNA binding nucleolar protein associated with rRNA transcription. The present study was undertaken to determine the mechanism of Nop25 localization in the nucleolus. Deletion experiments of Nop25 amino acid sequence showed Nop25 to contain a nuclear targeting sequence in the N-terminal and a nucleolar targeting sequence in the C-terminal. By expressing derivative peptides from the C-terminal as GFP-fusion proteins in the cells, a lysine and arginine residue-enriched peptide (KRKHPRRAQDSTKKPPSATRTSKTQRRRR) allowed a GFP-fusion protein to be transported and fully retained in the nucleolus. When the peptide was fused with cMyc epitope and expressed in the cells, a cMyc epitope was then detected in the nucleolus. Nop25 did not localize in the nucleolus by deletion of the peptide from Nop25. Furthermore, deletion of a subdomain (KRKHPRRAQ) in the peptide or amino acid substitution of lysine and arginine residues in the subdomain resulted in the loss ...
The long pentraxin PTX3 has multiple roles in innate immunity. For example, PTX3 regulates C1q binding to pathogens and dead cells and regulates their uptake by phagocytes. It also inhibits P-selectin-mediated...Full Text Available
LEW anti-DA kidney and DA anti-LEW kidney sera were assayed using an indirect 125I anti-immunoglobulin-binding assay with kidney homogenate as target. This allowed the full spectrum of antibodies to...Full Text Available
The yeast phosphatidylinositol transfer protein (Sec14p) is required for biogenesis of Golgi-derived transport vesicles and cell viability, and this essential Sec14p requirement is abrogated by inactivation...Full Text Available
We have identified another Drosophila GTP-binding protein (G protein) alpha subunit, dGq alpha-3. Transcripts encoding dGq alpha-3 are derived from alternative splicing of the dGq alpha locus previously...Full Text Available
sFlt-1 (soluble Flt-1) potently inhibits angiogenesis by binding extracellularly to VEGF (vascular endothelial growth factor). In the present paper, we report that hypoxia down-regulates sFlt-1 expression...Full Text Available
The H-D exchange reaction has been measured with the D2-H2O system, for Rhodobacter capsulatus JP91, which lacks the hupSL-encoded hydrogenase, and R. capsulatus BSE16, which lacks the HupUV proteins....Full Text Available
BackgroundTristetraprolin (TTP/ZFP36) family proteins have anti-inflammatory activity by binding to and destabilizing pro-inflammatory mRNAs such as Tnf mRNA, and represent a potential...Full Text Available
BackgroundEstrogen receptors alpha (ERα) and beta (ERβ) are transcription factors (TFs) that mediate estrogen signaling and define the hormone-responsive phenotype...Full Text Available
Friction opposes tooth motion whenever sliding mechanics is employed. Understanding what friction is and how to manage it is of paramount importance to the successful practitioner. In this article, the coefficients of friction are summarized between different arch wire-bracket couples as a function of material, geometric, and external parameters. From this vantage point, friction can then be evaluated within the context of other factors that affect sliding-binding and notching. PMID:9573878
Background: Protein disulfide isomerase (PDI) controls platelet integrin function, tissue-factor (TF) activation, and concentrates at fibrin and thrombus formation sites of vascular injury. Objective: We investigated involvement of surface thiol isomerases and especially PDI, in thrombin-mediated thrombin amplification on human platelets. Methods/Results: Using a new developed thrombin-dependent platelet thrombin generation assay we observed that the feedback activation of thrombin generation on the platelet surface does not depend on TF, as anti-TF antibodies inhibiting TF-induced thrombin formation in platelet-depleted plasma had no effect compared to vehicle-treated controls. Feedback activation of thrombin generation in the presence of platelets was significantly diminished by membrane impermeant thiol blockers or by the thiol isomerase-inhibitors bacitracin and anti-PDI antibody RL90, respectively. Platelet thrombin formation depends on binding of coagulation ...
Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder in childhood that is known to be associated with dopamine dysregulation. In this study, we investigated dopamine transporter (DAT) density in children with ADHD using iodine-123 labelled N-(3-iodopropen-2-yl)-2β-carbomethoxy-3β-(4-chlorophenyl) tropane ([{sup 123}I]IPT) single-photon emission tomography (SPET) and postulated that an alteration in DAT density in the basal ganglia is responsible for dopaminergic dysfunction in children with ADHD. Nine drug-naive children with ADHD and six normal children were included in the study. We performed brain SPET 2 h after the intravenous administration of [{sup 123}I]IPT and carried out both quantitative and qualitative analyses using the obtained SPET data, which were reconstructed for the assessment of the specific/non-specific DAT binding ratio in the basal ganglia. We then investigated the correlation between the severity ...
Several examples of the 14-membered, para-bridged ring system of the cyclopeptide alkaloids have been synthesized via an active ester cyclization. The yield of monomeric cyclopeptide varied from 1 to 33% and was affected by the amino acid substitution pattern and amide conformation of the linear peptide precursors. Both the synthetic models and a naturally occurring cyclopeptide alkaloid, ceanothine B, bind monovalent (Li"+) and divalent (Ca"2"+, Mg"2"+) cations. 4 figures, 1 table.
The mechanism of inactivation of cytochrome P450 2B1 (CYP2B1) by 4-tert-butylphenylacetylene (BPA) has been characterized previously to be caused by the covalent binding of a reactive...Full Text Available
In Borrelia burgdorferi (Bb), the Lyme disease spirochete, the alternative σ factor σ54 (RpoN) directly activates transcription of another alternative σ...Full Text Available
Bcl-2 homologues (such as Bcl-xL) promote survival in part through sequestration of “activator” BH3-only proteins (such as Puma), preventing them from directly activating...Full Text Available
Motor proteins couple steps in ATP binding and hydrolysis to conformational switching both in and remote from the active site. In our kinesin·AMPPPNP crystal structure, closure of the active...Full Text Available
The Ni(H_2O)_6 ion is located at an inversion center. Six octahedral water molecules surround the Ni"I"I ion and form hydrogen bonds with the sulfate groups. Each ammonium group binds to the sulfate groups through hydrogen bonds. (orig.).