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Biomedical subjects

S Vasudevan

Publications and source records attributed to S Vasudevan.

At least 19 recordsLinked to original sources
PubMed2004

Insertion of iodine in a functionalized inorganic layered solid.

The galleries of a Mg-Al layered double hydroxide have been functionalized by intercalation of (carboxymethyl)-beta-cyclodextrin cavities. The functionalized inorganic solid can adsorb iodine molecules from vapor as well as nonaqueous and aqueous solutions. The adsorbed iodine complexes with the grafted cyclodextrin cavities, disassociating heterolytically to form polyiodide species. Electronic and Raman spectra provide conclusive evidence for the existence of linear symmetric triodide, I(3)(-), and pentaiodide, I(5)(-), species within the cyclodextrin cavities confined in the layered double hydroxide.

Aluminum↗
PubMed2004

Sphingomyelin-cholesterol domains in phospholipid membranes: atomistic simulation.

We have carried out an atomic-level molecular dynamics simulation of a system of nanoscopic size containing a domain of 18:0 sphingomyelin and cholesterol embedded in a fully hydrated dioleylposphatidylcholine (DOPC) bilayer. To analyze the interaction between the domain and the surrounding phospholipid, we calculate order parameters and area per molecule as a function of molecule type and proximity to the domain. We propose an algorithm based on Voronoi tessellation for the calculation of the area per molecule of various constituents in this ternary mixture. The calculated areas per sphingomyelin and cholesterol are in agreement with previous simulations. The simulation reveals that the presence of the liquid-ordered domain changes the packing properties of DOPC bilayer at a distance as large as approximately 8 nm. We calculate electron density profiles and also calculate the difference in the thickness between the domain and the surrounding DOPC bilayer. The calculated difference in thickness is consistent with data obtained in atomic force microscopy experiments.

Algorithms↗
PubMed2003

Encapsulation of cobalt phthalocyanine in zeolite-y: evidence for nonplanar geometry.

Cobalt (II) phthalocyanine (CoPc) molecules have been encapsulated within the supercage of zeolite-Y. The square-planar complex, being larger than the almost spherical cage, is forced to adopt a distorted geometry on encapsulation. A comparative spectroscopic and magnetic investigation of CoPc encapsulated in zeolite-Y and in the unencapsulated state is reported. These results supported by molecular modeling have been used to understand the nature and extent of the loss of planarity of CoPc on encapsulation. The encapsulated molecule is shown to be the trans-diprotonated species in which the center of inversion is lost due to distortions required to accommodate the square complex within the zeolite. Encapsulation also leads to an enhancement of the magnetic moment of the CoPc. This is shown to be a consequence of the nonplanar geometry of the encapsulated molecule resulting in an excited high-spin state being thermally accessible.

Journal Article↗
PubMed2003

Structure of sphingomyelin bilayers: a simulation study.

We have carried out a molecular dynamics simulation of a hydrated 18:0 sphingomyelin lipid bilayer. The bilayer contained 1600 sphingomyelin (SM) molecules, and 50,592 water molecules. After construction and initial equilibration, the simulation was run for 3.8 ns at a constant temperature of 50 degrees C and a constant pressure of 1 atm. We present properties of the bilayer calculated from the simulation, and compare with experimental data and with properties of dipalmitoyl phosphatidylcholine (DPPC) bilayers. The SM bilayers are significantly more ordered and compact than DPPC bilayers at the same temperature. SM bilayers also exhibit significant intramolecular hydrogen bonding between phosphate ester oxygen and hydroxyl hydrogen atoms. This results in a decreased hydration in the polar region of the SM bilayer compared with DPPC. Since our simulation system is very large we have calculated the power spectrum of bilayer undulation and peristaltic modes, and we compare these data with similar calculations for DPPC bilayers. We find that the SM bilayer has significantly larger bending modulus and area compressibility compared to DPPC.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2001

Crystal structure of the von Willebrand factor modulator botrocetin.

The binding of von Willebrand factor (vWF) to the platelet receptor, glycoprotein (GP) Ib-IX-V complex, has a key role in the initiation of thrombus formation and is regulated by interactions with extracellular matrix components under the influence of hemodynamic forces. To a certain extent, these effects can be mimicked in vitro by two nonphysiologic modulators, ristocetin and botrocetin. The latter, isolated from the venom of the snake Bothrops jararaca, is a 31-kDa heterodimeric protein that forms a soluble complex with vWF. As an initial step toward understanding the mechanisms that regulate vWF function, we have solved the crystal structure of botrocetin at 1.8 A resolution. Botrocetin exhibits homology with other snake proteins, but contains only one metal binding site as compared to two in Factor IX binding protein and Factor IX/X binding protein and none in flavocetin. A distinctive feature of botrocetin is the presence of a negatively charged surface that may play a role in the association with the vWF A1 domain.

Amino Acid Sequence↗
PubMed2001

Regulated ARE-mediated mRNA decay in Saccharomyces cerevisiae.

The stability of several oncogene, cytokine, and growth factor transcripts is tightly regulated by signaling pathways through an ARE (AU-rich element) present in their 3'-UTRs. We have identified a yeast transcript, TIF51A, whose stability is regulated through its AU-rich 3'-UTR. We demonstrate that the mammalian TNFalpha and c-fos AREs regulate turnover of a reporter yeast transcript in a similar manner. AREs stabilize the transcript in glucose media and function as destabilizing elements in media lacking glucose or when the Hog1p/p38 MAP kinase pathway is inhibited. Significantly, both yeast and mammalian AREs promote deadenylation-dependent decapping in the yeast system. Furthermore, the yeast ELAV homolog, Pub1p, regulates the stability mediated by the TNFalpha ARE. These results demonstrate that yeast possess a regulatable mechanism for ARE-mediated decay and suggest conservation of this turnover process from yeast to humans.

3' Untranslated Regions↗
PubMed2000

Modeling and functional analysis of the interaction between von Willebrand factor A1 domain and glycoprotein Ibalpha.

Binding of the von Willebrand factor (vWF) A1 domain to the glycoprotein (GP) Ib-IX-V complex mediates platelet adhesion to reactive substrates under high shear stress conditions, a key event in hemostasis and thrombosis. We have now used the known three-dimensional structure of the A1 domain to model the interaction with the GP Ibalpha sequence 271-279, which has previously been implicated in ligand binding. Docking procedures suggested that A1 domain residues in strand beta3 and preceding loop (residues 559-566) as well as in helix alpha3 (residues 594-603) interact with Asp residues 272, 274, 277 and sulfated Tyr residues 278 and 279 in GP Ibalpha. To verify this model, 14 mutant A1 domain fragments containing single or multiple side chain substitutions were tested for their ability to mediate platelet adhesion under flow. Each of the vWF residues Tyr(565), Glu(596), and Lys(599) proved to be strictly required for A1 domain function, which, in agreement with previous findings, was also dependent on Gly(561). Moreover, an accessory functional role was apparent for a group of positively charged residues, including Arg at positions 629, 632, 636 and Lys at positions 643 and 645, possibly acting in concert. There was, however, no evidence from the model that these residues directly participate in forming the complex with GP Ibalpha. These results provide a partial model of the vWF-GP Ibalpha interaction linked to the manifestation of functional activity in platelet adhesion.

Amino Acids↗
PubMed2000

Detection of viral ribonucleic acid and histologic analysis of inflamed synovium in Ross River virus infection.

OBJECTIVE: To document the histology of Ross River virus (RRV) arthritis and to examine inflamed synovium for viral RNA. METHODS: Biopsy tissue from the inflamed knees of 12 patients with RRV infection was studied using conventional and immunostaining techniques. Reverse transcriptase-polymerase chain reaction technology was used to probe for the presence of viral RNA in the synovial biopsy samples and in serum. RESULTS: Hyperplasia of the synovial lining layer, vascular proliferation, and mononuclear cell infiltration were the main histologic changes. RRV RNA was found in knee biopsy tissue that was obtained from 2 patients at 5 weeks after the onset of symptoms. CONCLUSION: RRV RNA was identified in inflamed synovium more than a month after symptoms began. Inflammation was apparent in the absence of detectable virus in the majority of patients.

Adult↗
PubMed2000

The yeast hnRNP-like protein Hrp1/Nab4 marks a transcript for nonsense-mediated mRNA decay.

The nonsense-mediated mRNA decay (NMD) pathway monitors premature translation termination and degrades aberrant mRNAs. In yeast, it has been proposed that a surveillance complex searches 3' of a nonsense codon for a downstream sequence element (DSE) associated with RNA-binding proteins. An interaction between the complex and the DSE-binding protein(s) triggers NMD. Here we describe the identification and characterization of the Hrp1/Nab4 protein as a DSE-binding factor that activates NMD. Mutations in HRP1 stabilize nonsense-containing transcripts without affecting the decay of wild-type mRNAs. Hrp1p binds specifically to a DSE-containing RNA and interacts with Upf1p, a component of the surveillance complex. A mutation in HRP1 that stabilizes nonsense-containing mRNAs abolishes its affinity for the DSE and fails to interact with Upf1p. We present a model describing how Hrp1p marks a transcript for rapid decay.

Biological Transport↗
PubMed1999

Plasma and urinary selenium in Saudi Arabian patients with dilated cardiomyopathy.

We measured selenium (Se) levels in the urine and blood plasma samples of 72 Saudi Arabian patients with dilated cardiomyopathy (DCM) and 70 control subjects of the same origin. To correct for differences in the hydration state of the subjects, the selenium concentration for each urine sample was normalized by dividing it by the concentration of creatinine (CREAT) in the same sample. The median (and range) of the values found for the concentration of Se in plasma, urine, and normalized concentration in urine for the control subjects was 1.306 (0.66-2.50) microM, 0.478 (0.05-2.00) microM, and 56.7 (10.6-426.5) microM Se/M CREAT, respectively, whereas, for the patients, it was 1.246 (0.53-2.45) microM, 0.39 (0.05-1.90) microM, and 75.1 (4.9-656.2) microM Se/M CREAT, respectively. Additionally, the patients were separated into three subgroups according to the severity of their disease state as judged by NYHA procedure, and were then compared to the control group. Only group 4 (the most severe state of the disease) had a significantly lower concentration of urinary Se than the control group. However, the difference became nonsignificant when normalized for CREAT levels. There was no significant difference in the plasma Se levels between the controls and any of the patient groups. As the plasma Se in the control group and in the DCM patients both fell on the low end of the "normal" range, with the patients being marginally lower than the controls, there is no firm evidence from this study to suggest that Se is related to the high incidence rate of DCM found in Saudi Arabia.

Adolescent↗
PubMed1998

Mode of binding of anti-P-glycoprotein antibody MRK-16 to its antigen. A crystallographic and molecular modeling study.

Monoclonal antibody MRK-16 recognizes a discontinuous extracellular epitope on the multidrug resistance-associated ATP-binding cassette transporter, P-glycoprotein. The atomic basis for specificity of this antibody is of interest because of its potential as a modulator of P-glycoprotein activity. The crystal structure of Fab MRK-16 is reported to a resolution of 2.8 A. A structure for a portion of the epitope was derived by comparison to regions of solved structures with similar primary sequence. This has permitted a proposal for the mode of binding of the peptide epitope to the antibody, in which the peptide makes specific contacts with complementarity-determining regions H1, H2, and H3 from the heavy chain and L3 from the light chain. These interactions are consistent with epitope mapping studies and with the observation that MRK-16 is specific for human class I P-glycoprotein. This result identifies side chains in MRK-16 that would be amenable to alteration in antibody engineering experiments to derive improved multidrug resistance inhibitors for clinical use during chemotherapy. In particular, Arg-H97 contacts both Glu-746 and Asp-744 of the peptide, Arg-L96 contacts Asp-743, and Thr-H33 interacts with Thr-747. All of these epitope residues were implicated in mediating specificity by epitope mapping studies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Cycloheximide sensitivity of orotic acid biosynthesis induced by ammonia and glycine administration.

Administration of either ammonia or glycine to both rats and mice results in an increased synthesis in the liver and urinary excretion of orotic acid. The two most relevant observations obtained are that carbamoyl phosphate synthesized inside the mitochondria is involved in the increased synthesis of orotic acid and that this latter process is almost completely abolished by cycloheximide and actinomycin D, inhibitors of protein and RNA synthesis. Orotic acid synthesis could be controlled by an induction-suppression mechanism. Inhibition of synthesis of excess orotic acid brought about by N-(phosphonacetyl)-L-aspartic acid but not by acivicin, suggests that glutamine-dependent cytosolic synthesis of carbamoyl phosphate, is not involved. Administration of ornithine together with glycine completely suppressed the synthesis of orotic acid, but promoted a twofold increase of urea excretion. The concentration of ornithine rather than that of carbamoyl phosphate or the activity of the enzymes involved, may represent a limiting factor controlling both the flux of ammonia in the urea cycle and the availability of mitochondrial carbamoyl phosphate for orotic acid synthesis. Two enzymes have been found to be induced by glycine: ornithine decarboxylase and aspartate transcarbamoylase (aspartate carbamoyltransferase). Both enzymes may contribute to the increase in orotic acid synthesis, aspartate transcarbamoylase more directly and ornithine decarboxylase by lowering the ornithine concentration. Ornithine decarboxylase activity was completely suppressed but that of aspartate transcarbamoylase was further increased by cycloheximide treatment. Inhibition of orotic acid biosynthesis by cycloheximide appears to be the result of a decreased availability in the cytosol of carbamoyl phosphate synthesized inside the mitochondria.

Ammonium Chloride↗
PubMed1995

Characterization of the rat m3 muscarinic acetylcholine receptor produced in insect cells infected with recombinant baculovirus.

The m3 muscarinic acetylcholine receptor from rat heterologously produced in insect cells after infection with a recombinant baculovirus has an apparent molecular mass of approximately 75 kDa. Polyclonal antibodies raised against a carboxy-terminal nonapeptide that is unique to the m3 subtype can detect the receptors produced in the insect cells by Western blot and can also immunoprecipitate solubilized receptor. Immunofluorescence microscopy as well as electron microscopy revealed that the receptor was located intracellularly, visualized as a ring around the nucleus of the infected insect cells. Solubilization of the receptor was accomplished with digitonin which was added in increments (over 10 min) to a final concentration of 0.8% (mass/vol). The solubilized receptor is unstable when the ligand-binding site is not protected by a ligand. Here the low-affinity ligand propylbenzilylcholine (approximately 10 nM) has demonstrable protective ability during solubilization, but the usefulness of this ligand is limited by a very slow off rate. From the behaviour of the solubilized receptor during DEAE-Sephacel chromatography and lectin-affinity chromatography it can be deduced that the receptor produced in insect cells is heterogeneously glycosylated in the producing insect cells.

Affinity Labels↗