Biomedical subjects

S Wang

Publications and source records attributed to S Wang.

At least 145 records · Page 8Linked to original sources

PubMed2001

Oxidative dehydrogenation on the alpha-carbon of 4-pyridylacetonitrile complexes of pentaammineruthenium(II).

The oxidation of Ru(NH(3))(5)NCCH(2)py(2+) in 0.10 M HCl turns the solution from yellow to greenish blue with an absorption at lambda = 791 nm. The absorbance reaches its maximum value when the complex undergoes a two-electron oxidation. The IR and (1)H NMR spectra of the product indicate that the metal center remains as Ru(II) and that the ligand is oxidized. The (13)C NMR spectral results suggest that the oxidation product is [(NH(3))(5)RuNCC(pyH)C(pyH)CNRu(NH(3))(5)](ClO(4))(6). Cyclic voltammetry of the product solution also indicates that the oxidation proceeds in two one-electron steps corresponding to [Ru(III),Ru(II)] + e(-) <= => [Ru(II),Ru(II)] and [Ru(III),Ru(III)] + e(-) <= => [Ru(III),Ru(II)]. The structure of the product in deprotonated form [(NH(3))(5)RuNCC(py)C(py)CNRu(NH(3))(5)](ClO(4))(4)(H(2)O)(2) was determined crystallographically. [(NH(3))(5)RuNCC(py)C(py)CNRu(NH(3))(5)](ClO(4))(4)(H(2)O)(2) crystallizes in the orthorhombic Pbca space group with cell constants a = 13.7138 (16) A, b = 15.7553 (18) A, c = 17.831(2) A, and Z = 4. A mechanism for the oxidation has been proposed on the basis of the kinetic studies in the region of 0.01-0.20 M acid concentrations.

Journal Article↗

PubMed2001

Iridals are a novel class of ligands for phorbol ester receptors with modest selectivity for the RasGRP receptor subfamily.

Since 1990, the National Cancer Institute has performed extensive in vitro screening of compounds for anticancer activity. To date, more than 70 000 compounds have been screened for their antiproliferation activities against a panel of 60 human cancer cell lines. We probed this database to identify novel structural classes with a pattern of biological activity on these cell lines similar to that of the phorbol esters. The iridals form such a structural class. Using the program Autodock, we show that the iridals dock to the same position on the C1b domain of protein kinase C delta as do the phorbol esters, with the primary hydroxyl group of the iridal at the C3 position forming two hydrogen bonds with the amide group of Thr12 and with the carbonyl group of Leu 21 and the aldehyde oxygen of the iridal forming a hydrogen bond with the amide group of Gly23. Biological analysis of two iridals, NSC 631939 and NSC 631941, revealed that they bound to protein kinase C alpha with K(i) values of 75.6 +/- 1.3 and 83.6 +/- 1.5 nM, respectively. Protein kinase C is now recognized to represent only one of five families of proteins with C1 domains capable of high-affinity binding of diacylglycerol and the phorbol esters. NSC 631939 and NSC 631941 bound to RasGRP3, a phorbol ester receptor that directly links diacylglycerol/phorbol ester signaling with Ras activation, with K(i) values of 15.5 +/- 2.3 and 41.7 +/- 6.5 nM, respectively. Relative to phorbol 12,13-dibutyrate, they showed 15- and 6-fold selectivity for RasGRP3. Both compounds caused translocation of green fluorescent protein tagged RasGRP3 expressed in HEK293 cells, and both compounds induced phosphorylation of ERK1/2, a downstream indicator of Ras activation, in a RasGRP3-dependent fashion. We conclude that the iridals represent a promising structural motif for design of ligands for phorbol ester receptor family members.

Acrolein↗

PubMed2001

Fractionation of isotopically labeled peptides in quantitative proteomics.

The goal of quantitative proteomics is to examine the expression levels of all of the proteins in a biological system and recognize those that change as a function of some stimulus. Quantification is now frequently based on derivatization of peptides with isotopically distinguishable labeling agents. This study examines the extent to which isotopic forms of peptides having the same amino acid sequence are resolved by reversed-phase chromatography and assesses the degree to which resolution of these isotopically different forms of a peptide impact quantification. Three derivatizing agents were examined, the do and d3 forms of N-acetoxysuccinimide, the do and d4 forms of succinic anhydride, and the do and d8 forms of the commercial ICAT reagent Peptide mixtures from control and experimental samples were derivatized individually, mixed, subjected to reversed-phase chromatography, and analyzed by ESI-MS. When partial resolution of the isotopic forms of a peptide occurs, the largest error in assessing the true isotope ratio in a sample occurs when sampling at the extremes of a peak. Early in the elution of a peak, the sample will be enriched in the deuterated species, whereas the opposite is true at the tailing edge of a peak. Acetylated peptides showed the lowest degree of separation. Resolution of the deuterated and nondeuterated forms in this case was 0.023. This amounts to slightly over a 1-s difference in their peak maxima and can cause a typical error of +/- 6% at the leading and tailing edges of a peak. In contrast, resolution of the deuterated and nondeuterated forms of the ICAT reagent were calculated to be 0.45. This means that in a peak of 1-min width (W1/2), the peak maxima will vary by approximately 30 s, and measurement errors of -83 and +500% can occur at the leading and tailing edges of a peak. It is concluded that resolution of isotopic forms of a peptide can cause substantial quantification errors in quantitative proteomics.

Angiotensin I↗

PubMed2001

Control of hyperchaos.

A general method for controlling chaotic systems with one or more positive Lyapunov exponents is investigated analytically and numerically. The method retains the formal features of the adaptive adjustment mechanism and can be equally applied to various types of the unstable fixed points. It is shown that the method proposed here neither asks for any prior analytical knowledge of the system, nor any internal or external controlling parameters in advance.

Journal Article↗

PubMed2001

Canonical Hamiltonian gyrocenter variables and gauge invariant representation of the gyrokinetic equation.

By using the extended phase space Hamiltonian Lie-transform perturbation method, Hamiltonian canonical variables have been found to describe the motion of gyrocenters. A representation of the gyrokinetic equation has been established in terms of the magnetic moment M, the total energy U, and the canonical toroidal momentum P of the particle. This representation of the gyrokinetic equation is invariant with respect to the gauge transformation of perturbation fields. It explicitly reveals the effects of toroidal symmetry breaking, and it indicates the role that the perturbed canonical toroidal momentum plays in the gyrokinetic theory. In particular, it is found that the free energy associated with partial differential(P)f(0)(M,U,P) [here f(0)(M,U,P) is the equilibrium distribution function] does not have any nonadiabatic linear driving to the axisymmetric modes.

Journal Article↗

PubMed2001

Expression of eukaryotic translation initiation factors 4E and 2alpha is increased frequently in bronchioloalveolar but not in squamous cell carcinomas of the lung.

BACKGROUND: When resting cells are stimulated by growth factors, an increase in protein synthesis follows that depends in part on two key eukaryotic translation initiation factors, 4E and 2alpha (eIF-4E and eIF-2alpha, respectively). In the normal cell, expression and activity of both factors are increased transiently, whereas they become elevated constitutively in oncogene-transformed cultured cells, and overexpression of either initiation factor in rodent cells makes them tumorigenic. In this study, the authors investigated an association between the expression of these translation initiation factors and lung carcinogenesis. METHODS: The authors analyzed the expression of the protein synthesis initiation factors eIF-4E and eIF-2alpha by immunohistochemistry in bronchioloalveolar (BA) and squamous cell (SC) carcinomas of the lung. Western blot analysis was performed to validate the specificity of antibodies in detecting their cognate proteins. RESULTS: Both eIF-4E and eIF-2alpha were increased frequently in BA carcinomas, whereas only rarely did SC carcinomas demonstrate elevation of these translation initiation factors. An analysis of cyclin D1 expression did not show a strict correlation with the expression of eIF-4E and eIF-2alpha. CONCLUSIONS: Increased expression of either one or both translation initiation factors may facilitate accelerated growth and division of neoplastic cells in BA carcinoma of the lung. However, the current findings suggest a possibility that increased cell growth and proliferation in SC carcinoma may be achieved through a mechanism independent of increases in eIF-4E and eIF-2alpha expression.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2001

Glass-forming binaphthyl chromophores.

The use of the binaphthyl framework to synthesize glass-forming organic chromophores is described. Suzuki coupling reactions of racemic 6,6'-dibromo-2,2'-dialkoxy-1,1'-binaphthyl with 1,1-diphenyl-2-(4-dihydroxyboronphenyl)-ethene using [Pd(dppf)Cl2] (dppf = 1,1'-bis(diphenylphosphino)ferrocene) as the catalyst provide a set of chromophores with the 4-(2,2'-diphenylvinyl)-1-phenyl group at the 6- and 6'-positions and a range of groups on the oxygen atom. Starting with enantiomerically enriched (R)-6,6'-dibromo-2,2'-dihexyloxy-1,1'-binaphthyl ((R)-2Hex), one can obtain (R)-3Hex. Heck coupling reactions of 6,6'-dibromo-2,2'-dialkoxy-1,1'-binaphthyl compounds with styrene provide chromophores of the type 2,2'-dialkoxy-1,1'-binaphthyl-6,6'-bis(2-phenyl-vinyl). Starting with enantiomerically enriched (R)-2Hex, one obtains (R)-4Hex. Molecules of the type 4 contain two 1-naphthyl-2-phenyl ethylene chromophores with a pseudoorthogonal relationship. Similar procedures can be used to obtain fragments with more extended conjugation length. Thus, the Heck coupling reaction of 2Hex with 4-(4'-tert-butylstyryl)styrene, 1-(4'-tert-butylstyryl)-4-(4'-vinylstyryl)benzene, and 1-(3',5'-dihexyloxystyryl)4-(4'-vinylstyryl)benzene provides 5Hex, 6Hex, and 7Hex, respectively. DSC measurements and powder diffraction experiments indicate that the binaphthol chromophores show a resistance to crystallization. In some cases, considerably different thermal behavior is observed between enantiomerically enriched samples and their racemic counterparts. Increasing the size of the conjugated fragment on the binaphthol core leads to materials with higher glass-transition temperatures and a less pronounced tendency to crystallize. Fluorescence spectroscopy gives evidence of "excimer"-type interactions in the solid state, except for the chromophores with 4-(2,2'-diphenylvinyl)-1-phenyl groups. It is possible to obtain amorphous films of these chromophores directly from solution, and to fabricate light-emitting diodes, in which the electroluminescent layer corresponds to the binaphthyl chromophore.

Journal Article↗

PubMed2001

The spatiotemporal relationship among Schwann cells, axons and postsynaptic acetylcholine receptor regions during muscle reinnervation in aged rats.

To morphologically define the aging-related features during muscle reinnervation the spatiotemporal relationships among the major components of the neuromuscular junctions (NMJs) were investigated. A total of 64 rats, 30 adults (4 months old) and 34 aged adults (24 months old), were used. Between 1 and 12 weeks after sciatic nerve-crushing injury, cryosections of skeletal muscle were single or double labeled for S100, a marker of Schwann cells (SCs), for protein gene product 9.5, a neuronal marker, and for alpha-bungarotoxin (alpha-BT), a marker of the acetylcholine receptor site (AChR site), and then observed by confocal laser microscopy. The most obvious age changes were noted: (1) the regenerating SCs and axons were delayed in their arrival at the NMJ, (2) the dimensions of terminal SCs and AChR sites displayed a drastic and long-lasting drop (for terminal SCs, during 1-8 weeks; for AChR sites, during 1-12 weeks); (3) the degree of spatial overlap between AChR sites and terminal SCs was markedly low until 8 weeks post-crush; (4) damage and poor formation in the SCs, terminal axons and AChR sites, together with poor process extension from the terminal SC or terminal axon, were pronounced; (5) persistent aberrant changes, such as multiple innervation and terminal axon sprouting, together with poorly formed collateral innervation, nerve bundles, and NMJs, more frequently occurred in the later reinnervation period. Thus, with aging, regeneration is impaired during the period in which regenerating SC strands and axons extend into NMJs and the subsequent establishment of nerve-muscle contact is in progress. A complex set of morphological abnormalities between or among the TSCs, terminal axons, and AChR sites may be important in slowing of regeneration and reinnervation in aged motor endplates.

Aging↗

PubMed2001

Molecular studies of CFTR interacting proteins.

Transport via the cystic fibrosis transmembrane conductance regulator (CFTR) is activated by its interactions with cytoplasmic cofactors, such as cAMP-activated protein kinases. CFTR activity is also known to couple to other ion channels and transporters. Although the genetic cause of human cystic fibrosis by CFTR mutations has been well established, little is known about the protein machinery that plays a role in linking the CFTR to other regulatory or ion-conducting proteins. Several regions of CFTR proteins are highly conserved among different species. The conserved motifs are thought to determine various aspects of channel and mediate interactions with other regulatory proteins. The C-termini, which are not required for functional expression of the CFTR chloride conductance, are also highly conserved. Several proteins that interact with the conserved C-terminus have now been identified. They contain several distinct protein interaction domains, which may be involved in the assembly of macromolecular CFTR channel complexes in vivo. Molecular understanding of these proteins may provide important insights into CFTR function in cystic fibrosis.

Cyclic AMP-Dependent Protein Kinases↗

PubMed2001

Stabilizing unstable discrete systems.

A general method for stabilizing unstable discrete systems to a fixed point or high-period orbit is developed analytically and numerically in this paper. It is shown that the method can be equally applied to the systems with one or more positive Lyapunov exponents. Moreover, the method does not require a prior analytical knowledge of the system under investigation, nor any additional control parameters.

Journal Article↗

PubMed2001

Measurements of radiation near an atomic spectral line from the interaction of a 30 GeV electron beam and a long plasma.

Emissions produced or initiated by a 30-GeV electron beam propagating through a approximately 1-m long heat pipe oven containing neutral and partially ionized vapor have been measured near atomic spectral lines in a beam-plasma wakefield experiment. The Cerenkov spatial profile has been studied as a function of oven temperature and pressure, observation wavelength, and ionizing laser intensity and delay. The Cerenkov peak angle is affected by the creation of plasma, and estimates of neutral and plasma density have been extracted. Increases in visible background radiation, consistent with increased plasma recombination emissions due to dissipation of wakefields, were simultaneously measured.

Journal Article↗

PubMed2001

Synthesis and evaluation of the sunflower derived trypsin inhibitor as a potent inhibitor of the type II transmembrane serine protease, matriptase.

We report here the synthesis of a 14-amino acid long bicyclic peptide, previously isolated from sunflower seeds. This peptide, termed sunflower trypsin inhibitor (SFTI-1), is one of the most potent naturally occurring small-molecule trypsin inhibitors. In addition to inhibiting trypsin, the synthetic SFTI-1 is also a very potent inhibitor, with a K(i) of 0.92nM, of the recently identified epithelial serine protease, termed 'matriptase'.

Amino Acid Sequence↗

PubMed2001

The effects of pokeweed mitogen (PWM) and phytohemagglutinin (PHA) on bovine oocyte maturation and embryo development in vitro.

The effects of two commonly used cell culture mitogens, pokeweed (PWM) and phytohemagglutinin (PHA) on bovine oocyte maturation in vitro (IVM) and preimplantation embryo development in vitro were evaluated by randomized complete block experimental design with three treatments. Effects were measured by quantifying subsequent embryo development. Oocyte maturation was adversely affected by PWM-containing medium as indicated by a decrease in cleavage rate and subsequent embryo development to morula and blastocyst stages. Embryo developmental competence was also adversely affected by PWM. Development in PHA-containing medium was significantly better (P<0.05) than in the PWM treatment, although there was no difference (P>0.05) when compared to Control. We conclude that there are no beneficial effects in adding mitogenic agents to culture medium to enhance in vitro embryo production and development.

Animals↗

PubMed2001

Effect of insulinotropic agent nateglinide on Kv and Ca(2+) channels in pancreatic beta-cell.

Novel insulinotropic agent nateglinide stimulates insulin via binding to sulfonylurea receptor and closing the ATP-dependent K+ (K(ATP)) channels in pancreatic beta-cells, leading to an increase in [Ca(2+)](i) for exocytosis. The voltage-dependent Ca(2+) channel and the delayed rectifier K+ (Kv) channels are also present in beta-cells and their activities determine the configuration of action potential and hence contribute to the regulation of [Ca(2+)](i) and insulin secretion. This study, by using the patch-clamp method in whole cell configuration, comparatively characterized the direct effects of sulfonylurea receptor ligands including nateglinide, glyburide, and repaglinide on Kv and Ca(2+) channels. Each agent inhibited Kv currents in a concentration-dependent manner with effective concentration range two to three orders higher than that for blocking K(ATP) channels. A marginal stimulation of Ca(2+) current was observed with all drugs, while repaglinide at concentration greater than 300 nM inhibited Ca(2+) current. The direct effects of these antidiabetic agents on Kv and Ca(2+) channels may act concertedly with their primary action on K(ATP) channels in regulating [Ca(2+)](i) and the stimulus-secretion coupling.

Animals↗

PubMed2001

p38 MAP kinase mediates nitric oxide-induced apoptosis of neural progenitor cells.

Neural progenitor cells (NPC) can proliferate, differentiate into neurons or glial cells, or undergo a form of programmed cell death called apoptosis. Although death of NPC occurs during development of the nervous system and in the adult, the underlying mechanisms are unknown. Here we show that nitric oxide (NO) can induce death of C17.2 NPC by a mechanism requiring activation of p38 MAP kinase, poly(ADP-ribose) polymerase, and caspase-3. Nitric oxide causes release of cytochrome c from mitochondria, and Bcl-2 protects the neural progenitor cells against nitric oxide-induced death, consistent with a pivotal role for mitochondrial changes in controlling the cell death process. Inhibition of p38 MAP kinase by SB203580 abolished NO-induced cell death, cytochrome c release, and activation of caspase-3, indicating that p38 activation serves as an upstream mediator in the cell death process. The anti-apoptotic protein Bcl-2 protected NPC against nitric oxide-induced apoptosis and suppressed activation of p38 MAP kinase. The ability of nitric oxide to trigger death of NPC by a mechanism involving p38 MAP kinase suggests that this diffusible gas may regulate NPC fate in physiological and pathological settings in which NO is produced.

Animals↗

PubMed2001

Functional interaction of Jun and homeodomain proteins.

We have used the yeast two-hybrid system to identify proteins that interact with the N-terminal region of c-Jun, which is known to be involved in regulatory interactions. One of the proteins identified is the homeodomain-containing protein Hex. The Hex homeodomain is sufficient for interaction; moreover, the homeodomains of several other transcription factors also interact. Mutations within helix III of the Hex homeodomain greatly reduce the interaction. In vitro, c-Jun/c-Fos, JunB/c-Fos, and JunD/c-Fos all interact with the Hex homeodomain more strongly than the respective Jun proteins (or c-Fos) alone, suggesting that heterodimerization exposes reactive regions in the N termini of the Jun proteins. In transfected cells, Hex expression inhibits Jun- or Jun/c-Fos-dependent transcription of a reporter gene; the presence of Hex-binding sites in the promoter enhances the inhibitory effect. Jun-dependent activation of transcription from the basic fibroblast growth factor gene, previously shown to be regulated by both Jun and homeodomain proteins, was also dramatically reduced by Hex expression. Furthermore, in contrast to the reduction of Jun-mediated transcription by Hex, we found that expression of the Drosophila ultrabithorax gene enhanced c-Jun-dependent transcription. We conclude that the functional interaction between members of the Jun and homeodomain families of transcription factors could play a critical role in regulating developmental and differentiation programs.

Animals↗

PubMed2001

Alcohol hypersensitivity, increased locomotion, and spontaneous myoclonus in mice lacking the potassium channels Kv3.1 and Kv3.3.

The Shaw-like potassium (K(+)) channels Kv3.1 and Kv3.3 are widely coexpressed in distinct neuronal populations in the CNS, possibly explaining the relatively "mild" phenotypes of the Kv3.1 and the Kv3.3 single mutant. Kv3.1-deficient mice show increased cortical gamma- and decreased delta-oscillations (Joho et al., 1997, 1999); otherwise, the Kv3.1-mutant phenotype is relatively subtle (Ho et al., 1997; Sánchez et al., 2000). Kv3.3-deficient mice display no overt phenotype (Chan, 1997). To investigate whether Kv3.1 and Kv3.3 K(+) channels are functionally redundant, we generated the Kv3.1/Kv3.3 double mutant. Kv3.1/Kv3.3-deficient mice were born at the expected Mendelian frequencies indicating that neither Kv3.1 nor Kv3.3 K(+) channels are essential for embryonic development. Although there are no obvious changes in gross brain anatomy, adult Kv3.1/Kv3.3-deficient mice display severe ataxia, tremulous movements, myoclonus, and hypersensitivity to ethanol. Mice appear unbalanced when moving, whereas at rest they exhibit whole-body jerks every few seconds. In spite of the severe motor impairment, Kv3.1/Kv3.3-deficient mice are hyperactive, show increased exploratory activity, and display no obvious learning or memory deficit. Myoclonus, tremor, and ethanol hypersensitivity are only seen in the double-homozygous Kv3.1/Kv3.3-deficient mice, whereas increased locomotor and exploratory activity are also present in double-heterozygous mice. The graded penetrance of mutant traits appears to depend on the number of null alleles, suggesting that some of the distinct phenotypic traits visible in the absence of Kv3.1 and Kv3.3 K(+) channels are unrelated and may be caused by localized dysfunction in different brain regions.

Animals↗

PubMed2001

Model-independent source imaging using two-pion correlations in (2 to 8)a GeV Au+Au collisions.

We report a particle source imaging analysis based on two-pion correlations in high multiplicity Au+Au collisions at beam energies between 2A and 8A GeV. We apply the imaging technique introduced by Brown and Danielewicz, which allows a model-independent extraction of source functions with useful accuracy out to relative pion separations of about 20 fm. The extracted source functions have Gaussian shapes. Values of source functions at zero separation are almost constant across the energy range under study. Imaging results are found to be consistent with conventional source parameters obtained from a multidimensional Hanburg-Brown-Twiss analysis.

Journal Article↗