Biomedical subjects

X Li

Publications and source records attributed to X Li.

At least 271 records · Page 15Linked to original sources

PubMed2001

Three monoalkoxy-substituted nido-platinaboranes: [(PPh3)2PtB10H11-8-(OCH3)], [(PPh3)2PtB10H11-8-[OCH-(CH3)2]] and [(PPh3)2PtB10H10-9-[OCH(CH3)2]].

Each of the title compounds, 8-methoxy-7,7-bis(triphenylphosphine-P)-8,9:10,11-di-muH-7-platina-nido-undecaborane dichloromethane hemisolvate, [Pt(CH(14)B(10)O)(C(18)H(15)P)(2)].0.5CH(2)Cl(2), (I), 8-isopropoxy-7,7-bis(triphenylphosphine-P)-8,9:10,11-di-muH-7-platina-nido-undecaborane dichloromethane solvate, [Pt(C(3)H(18)B(10)O)(C(18)H(15)P)(2)].CH(2)Cl(2), (II), and 9-isopropoxy-7,7-bis(triphenylphosphine-P)-8,9:10,11-di-muH-7-platina-nido-undecaborane dichloromethane solvate, [Pt(C(3)H(18)B(10)O)(C(18)H(15)P)(2)].CH(2)Cl(2), (III), has an 11-vertex nido polyhedral skeleton, with the 7-platinum centre ligating to two exo-polyhedral PPh(3) groups and an alkoxy-substituted polyhedral borane ligand. Compounds (II) and (III) are isomers. The Pt-B distances are in the range 2.214 (7)-2.303 (7) A for (I), 2.178 (16)-2.326 (16) A for (II) and 2.205 (6)-2.327 (6) A for (III).

Journal Article↗

PubMed2001

15N and 31P solid-state NMR investigations on the orientation of zervamicin II and alamethicin in phosphatidylcholine membranes.

The topologies of zervamicin II and alamethicin, labeled with (15)N uniformly, selectively, or specifically, have been investigated by oriented proton-decoupled (15)N solid-state NMR spectroscopy. Whereas at lipid-to-peptide (L/P) ratios of 50 (wt/wt) zervamicin II exhibits transmembrane alignments in 1,2-dicapryl (di-C10:0-PC) and 1,2-dilauroyl (di-C12:0-PC) phosphatidylcholine bilayers, it adopts orientations predominantly parallel to the membrane surface when the lengths of the fatty acyl chains are extended. The orientational order of zervamicin II increases with higher phospholipid concentrations, and considerable line narrowing is obtained in di-C10:0-PC/zervamicin II membranes at L/P ratios of 100 (wt/wt). In contrast to zervamicin, alamethicin is transmembrane throughout most, if not all, of its length when reconstituted into 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayers. The (31)P solid-state NMR spectra of all phospholipid/peptaibol samples investigated show a high degree of headgroup order, indicating that the peptides do not distort the bilayer structure. The observed differences in peptide orientation between zervamicin and alamethicin are discussed with reference to differences in their lengths, helical conformations, distribution of (hydroxy)proline residues, and hydrophobic moments. Possible implications for peptaibol voltage-gating are also described.

Alamethicin↗

PubMed2001

Experimental factors controlling analyte ion generation in laser desorption/ionization mass spectrometry on porous silicon.

Desorption/ionization on porous silicon (DIOS) is a relatively new laser desorption/ionization technique for the direct mass spectrometric analysis of a wide variety of samples without the requirement of a matrix. Porous silicon substrates were fabricated using the recently developed nonelectrochemical H2O2-metal-HF etching as a versatile platform for investigating the effects of morphology and physical properties of porous silicon on DIOS-MS performance. In addition, laser wavelength, mode of ion detection, pH, and solvent contributions to the desorption/ionization process were studied. Other porous substrates such as GaAs and GaN, with similar surface characteristics but differing in thermal and optical properties from porous silicon, allowed the roles of surface area, optical absorption, and thermal conductivities in the desorption/ionization process to be investigated. Among the porous semiconductors studied, only porous silicon has the combination of large surface area, optical absorption, and thermal conductivity required for efficient analyte ion generation under the conditions studied. In addition to these substrate-related factors, surface wetting, determined by the interaction of deposition solvent with the surface, and charge state of the peptide were found to be important in determining ion generation efficiency.

Hydrogen-Ion Concentration↗

PubMed2001

Protein phosphatase 2A and its B56 regulatory subunit inhibit Wnt signaling in Xenopus.

Wnt signaling increases beta-catenin abundance and transcription of Wnt-responsive genes. Our previous work suggested that the B56 regulatory subunit of protein phosphatase 2A (PP2A) inhibits Wnt signaling. Okadaic acid (a phosphatase inhibitor) increases, while B56 expression reduces, beta-catenin abundance; B56 also reduces transcription of Wnt-responsive genes. Okadaic acid is a tumor promoter, and the structural A subunit of PP2A is mutated in multiple cancers. Taken together, the evidence suggests that PP2A is a tumor suppressor. However, other studies suggest that PP2A activates Wnt signaling. We now show that the B56, A and catalytic C subunits of PP2A each have ventralizing activity in Xenopus embryos. B56 was epistatically positioned downstream of GSK3beta and axin but upstream of beta-catenin, and axin co-immunoprecipitated B56, A and C subunits, suggesting that PP2A:B56 is in the beta-catenin degradation complex. PP2A appears to be essential for beta-catenin degradation, since beta-catenin degradation was reconstituted in phosphatase-depleted Xenopus egg extracts by PP2A, but not PP1. These results support the hypothesis that PP2A:B56 directly inhibits Wnt signaling and plays a role in development and carcinogenesis.

Animals↗

PubMed2001

The role of caveolae and caveolin in vesicle-dependent and vesicle-independent trafficking.

Caveolae can mediate endocytosis, transcytosis, and potocytosis. Our understanding of these processes as well as the elucidation of the molecular machinery involved has greatly expanded. In addition, caveolin, a 22 kDa protein often associated with caveolae, can promote the trafficking of sterol through the cytoplasm independent of vesicles. Caveolin also influences the formation, morphology, and function of caveolae. The ability of caveolae and caveolin to mediate macromolecular transport directly impacts a variety of physiological and pathophysiological processes.

Animals↗

PubMed2001

CARD4/Nod1 mediates NF-kappaB and JNK activation by invasive Shigella flexneri.

Epithelial cells are refractory to extracellular lipopolysaccharide (LPS), yet when presented inside the cell, it is capable of initiating an inflammatory response. Using invasive Shigella flexneri to deliver LPS into the cytosol, we examined how this factor, once intracellular, activates both NF-kappaB and c-Jun N-terminal kinase (JNK). Surprisingly, the mode of activation is distinct from that induced by toll-like receptors (TLRs), which mediate LPS responsiveness from the outside-in. Instead, our findings demonstrate that this response is mediated by a cytosolic, plant disease resistance-like protein called CARD4/Nod1. Biochemical studies reveal enhanced oligomerization of CARD4 upon S. flexneri infection, an event necessary for NF-kappaB induction. Dominant-negative versions of CARD4 block activation of NF-kappaB and JNK by S. flexneri as well as microinjected LPS. Finally, we showed that invasive S. flexneri triggers the formation of a transient complex involving CARD4, RICK and the IKK complex. This study demonstrates that in addition to the extracellular LPS sensing system mediated by TLRs, mammalian cells also possess a cytoplasmic means of LPS detection via a molecule that is related to plant disease-resistance proteins.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Vascular endothelial growth factor-B-deficient mice display an atrial conduction defect.

BACKGROUND: Vascular endothelial growth factors (VEGFs) and their receptors are essential regulators of vasculogenesis and angiogenesis in both embryos and adults. One of the factors with a still unknown physiological function is VEGF-B, which is expressed in many tissues, including the heart. METHODS AND RESULTS: Mice carrying a targeted deletion in the VEGF-B gene were developed. In VEGF-B(-/-) animals, no gross abnormalities were observed in organs that normally show high expression of VEGF-B, such as the heart, muscle, and kidney. Analysis of heart function by ECG showed that adult VEGF-B(-/-) mice have an atrial conduction abnormality characterized by a prolonged PQ interval. VEGF- or basic fibroblast growth factor-induced corneal angiogenesis was similar in normal and VEGF-B(-/-) mice. CONCLUSIONS: VEGF-B seems to be required for normal heart function in adult animals but is not required for proper development of the cardiovascular system either during development or for angiogenesis in adults.

Animals↗

PubMed2001

Investigation on a novel core-coated microspheres protein delivery system.

Among the different approaches to achieve protein delivery, the use of polymers, specifically biodegraded, holds great promise. In this work, a new microsphere delivery system composed of alginate microcores surrounded by a biodegradable poly-DL-lactide-poly(ethylene glycol (PELA) was designed to improve the loading efficiency and stability of proteins. Alginate was solidified by calcium (MS-1), polylysine (MS-2) and chitosan (MS-3), respectively, to form different microcores. Human Serum Albumin (HSA), used as a model protein, was efficiently entrapped within the alginate microcores using a high-speed stirrer and then microencapsulated into PELA copolymer using a w/o/w solvent extraction method. DSC analysis of the microspheres revealed the efficient encapsulation of the alginate microcores, while the microcores were dispersed in the PELA matrix. SDS-PAGE results showed that HSA kept its structural integrity during encapsulation and release procedure. Microspheres were characterized in terms of morphology, size, loading efficiency, in vitro degradation and protein release. The degradation profiles were characterized by measuring the loss of microsphere mass, the decrease of polymer intrinsic viscosity and the reduction of PEG content of PELA coat. The release profiles were investigated from the measurement of protein presented in the release medium at various intervals. The results were that the degradation rate of these core-coated microspheres was MS-2>MS-1>MS-3. The extent of burst release from the core-coated microspheres in the initial protein release was lower than the 27% burst release from the conventional microspheres. In conclusion, the work presents a new approach for macromolecular drugs (such as protein, peptide drugs) delivery. The core-coated microspheres system may have potential use as a carrier for drugs that are poorly absorbed after oral administration.

Alginates↗

PubMed2001

Crystal structure of an aldehyde reductase Y50F mutant-NADP complex and its implications for substrate binding.

Pig aldehyde reductase containing the active site mutation tyrosine(50) to phenylalanine has been crystallized in the presence of the cofactor NADP(H) to a resolution of 2.2 A. This structure clearly shows loss of the tyrosine hydroxyl group and no other significant perturbations compared with previously determined structures. The mutant binds cofactor (both oxidized and reduced) more tightly than the wild-type enzyme but shows a complete lack of binding of the aldehyde reductase inhibitor barbitone, as determined by fluorescence titrations. Numerous attempts at preparing a ternary complex with a range of small aldehyde substrates were unsuccessful. This result, in addition to the inability of the mutant protein to bind the inhibitor, provides strong evidence for the proposal that the tyrosine hydroxyl group is essential for substrate binding in addition to catalysis.

Alcohol Oxidoreductases↗

PubMed2001

Effect of a long-acting beta2-agonist over three months on airway wall vascular remodeling in asthma.

There are few data regarding the potential effects of antiasthma treatment on indices of airway remodeling, such as the increased subepithelial airway vascularity in patients with asthma. We studied 45 symptomatic subjects with asthma who were receiving treatment with low dose inhaled corticosteroids (ICS) (range 200-500 microg twice a day) and 28 normal subjects without asthma as a control population. Subjects underwent bronchoscopy with airway biopsy and subjects with asthma were then randomized to receive supplementary inhaled salmeterol 50 microg twice a day, fluticasone propionate 100 microg twice a day, or placebo for 3 mo in addition to their baseline ICS. Biopsy of the airway was then repeated. The biopsies were analyzed for vascular structures in the subepithelial lamina propria. Sufficient biopsy material was available for analysis of vascularity in 34 of the subjects with asthma and 28 of the normal subjects. We confirmed that airways of subjects with asthma had a significant increase in the number of vessels/mm2 of lamina propria compared with airways of normal subjects (524 +/- 137 vessels/mm2, n = 34 versus 425 +/- 130 vessels/mm2, n = 28; p = 0.004). There was a decrease in the density of vessels of lamina propria after treatment only in the salmeterol group compared with baseline (before, 535 +/- 153 vessels/mm2 versus after, 400 +/- 142 vessels/mm2; n = 12; p = 0.04). There was no significant change within the fluticasone (n = 11) or placebo (n = 11) treatment groups, but also no significant differences between the groups. Notably, no treatment was associated with increased airway wall vascularity. The demonstrated fall in vessel number within the salmeterol-treated group may suggest an advantageous effect of long-acting beta2-agonists on this manifestation of airway remodeling over the 3-mo time scale of this study, which is complementary to the action of ICS on airway vascularity.

Adrenergic beta-Agonists↗

PubMed2001

Efficient asymmetric synthesis of biologically important tryptophan analogues via a palladium-mediated heteroannulation reaction.

A novel and concise synthesis of optically active tryptophan derivatives was developed via a palladium-catalyzed heteroannulation reaction of substituted o-iodoanilines with an internal alkyne. The required internal alkyne 14a or 25 was prepared in greater than 96% de via alkylation of the Schöllkopf chiral auxiliary 19 employing diphenyl phosphate as the leaving group. The Schöllkopf chiral auxiliary was chosen here for the preparation of L-tryptophans would be available from D-valine while the D-isomers required for natural product total synthesis would originate from the inexpensive L-valine (300-g scale). Applications of the palladium-catalyzed heteroannulation reaction were extended to the first asymmetric synthesis of L-isotryptophan 38 and L-benz[f]tryptophan 39. More importantly, the optically pure 6-methoxy-D-tryptophan 62 was prepared by this protocol on a large scale (>300 g). This should permit entry into many ring-A oxygenated indole alkaloids when coupled with the asymmetric Pictet-Spengler reaction. In addition, an improved total synthesis of tryprostatin A (9a) was accomplished in 43% overall yield employing this palladium-mediated process.

Alkylation↗

PubMed2001

Formation of two-dimensional concentration pulses on microdesigned composite catalyst surfaces.

We study the effect of microdesigned composite geometries on pattern formation during the catalytic oxidation of CO on Pt-Ti, Pt-Rh, and Pt-Pd composite catalysts. In particular, we find experimentally (and rationalize through modeling) that adsorbate surface transport through the second (active) component drastically affects the shapes and interactions of concentration patterns (traveling pulses) observed on pure Pt.

Journal Article↗

PubMed2001

Sequence, protein expression and extracellular-regulated kinase association of the hyaladherin RHAMM (receptor for hyaluronan mediated motility) in PC12 cells.

Differentiation of PC12 cells by nerve growth factor (NGF) or fibroblast growth factor-2 (FGF2) is dependent on signaling mediated by extracellular regulated kinase (ERK). We investigated the involvement of receptor for hyaluronan mediated motility (RHAMM) in this signaling pathway. A single RHAMM 3.2 kb transcript was detected in PC12 RNA. Reverse transcriptase-polymerase chain reaction generated a 2141 bp cDNA that had identical sequence to rat brain RHAMM and showed no evidence of alternate splicing. Several RHAMM species were identified by Western blotting. Immunohistochemistry showed RHAMM localization to the cytoskeleton, neurites and growth cones. Following stimulation of PC12 cells with NGF or FGF2 RHAMM was co-immunoprecipitated by phosphorylation-specific anti-ERK antibodies, indicating a role for RHAMM in ERK signaling in PC12 cells.

Amino Acid Sequence↗

PubMed2001

CSN3 interacts with IKKgamma and inhibits TNF- but not IL-1-induced NF-kappaB activation.

The transcription factor nuclear factor kappaB (NF-kappaB) plays a pivotal role in immune and inflammatory responses. Activation of NF-kappaB requires the activity of IKK, a kinase complex that contains two catalytic subunits, IKKalpha and IKKbeta, and a regulatory subunit IKKgamma. To understand how IKK activity is regulated, we searched for IKKgamma-interacting proteins by the yeast two-hybrid system. These screenings identified CSN3, a component of the COP9 signalsome, as a protein specifically interacting with IKKgamma. Overexpression of CSN3 inhibits NF-kappaB activation triggered by tumor necrosis factor (TNF), but not interleukin-1 (IL-1). Moreover, overexpression of CSN3 also inhibits NF-kappaB activation triggered by proteins involved in TNF signaling, including TNF-R1, TRAF2, RIP, and NIK, but not by TRAF6, a protein involved in IL-1 signaling. These data suggest that CSN3 is a specific negative regulator of TNF- but not IL-1-induced NF-kappaB activation pathways.

Blotting, Western↗

PubMed2001

catena-Poly[europium-tri-mu-4-methyl-benzoato].

Each Eu3+ ion in the title compound, catena-poly[europium(III)-tri-mu-4-methylbenzoato-O:O,O';O:O,O';O,O':O'], [[Eu(C8H7O2)3]3]n, is coordinated by nine O atoms, and three Eu atoms form a trimeric unit. These trimeric units are linked by bridging-chelating carboxylates to form an infinite one-dimensional polymer chain.

Journal Article↗

PubMed2001

Recruitment of the male-specific lethal (MSL) dosage compensation complex to an autosomally integrated roX chromatin entry site correlates with an increased expression of an adjacent reporter gene in male Drosophila.

Drosophila dosage compensate (equalize X-linked gene products) by doubling the transcription of most X-linked genes in males. The MSL (male-specific lethal) ribonucleoprotein complex consisting of at least five proteins and two non-coding RNAs (roX1 and roX2) is essential for this transcription response. Recently it has been shown that the X-linked roX1 and roX2 genes each contain at least one chromatin entry site for the MSL complex. In this study we show that insertion of either roX1 or roX2 DNA sequences, upstream of an insulated lacZ reporter gene controlled with the constitutive armadillo promoter (arm-lacZ), results in a significant elevation of expression of lacZ in males. However, full compensation, that is a precise doubling of lacZ expression in males relative to females, was only observed in some lines carrying autosomal insertions of either roX1-arm-lacZ or roX2-arm-lacZ transgenes. Furthermore, we found that a 419-base pair fragment of roX1 that contains an MSL binding site was sufficient to cause a modest elevation of expression of lacZ in males, but this response was significantly less than obtained with a full-length roX1 cDNA. This is the first direct demonstration that insertion of an MSL chromatin entry site on an autosome results in elevated expression in males of genes near the entry site.

Animals↗

PubMed2001

[The study of beta-2 adrenergic receptors gene transferred into cardiomyocytes by adenovirus vectors contain different promoter].

OBJECTIVE: To observe human beta(2) adrenergic receptors (beta(2)-AR) gene expression in cardiomyocytes transfected by adenoviral vector contain cmv or mlc-2v promoter. METHODS: Two adenoviral vectors (Adcmv beta(2) AR, Admlc beta(2) AR) were constructed, in which beta(2)-AR gene is under control of either the ventricle-specific myosin light chain-2 (mlc-2v) or the cmv promoter. The cultured neonate rat ventricular myocytes were infected by two adenoviral vectors, and the beta(2)-AR expression of on cultured neonate rat ventricular myocytes and their ability to potentiate beta-adrenergic signaling were assessed. RESULTS: The presence of beta(2)-AR mRNA was detected by RT-PCR, and the expression of the beta(2)-AR gene was demonstrated by protein immunoblots. According to a ligand binding assay, the density of beta-AR in the cardiomyocytes infected by Admlc beta(2) AR and Adcmv beta(2) AR was greater than that in the control. Moreover, the latter was higher than the former (234 +/- 6.4 fmol/mg protein vs 153 +/- 5.2 fmol/mg protein) (P < 0.01). It was demonstrated that beta(2)-AR gene significantly increased isoproterenol stimulated cAMP in cardiomyocytes. CONCLUSION: The results above demonstrated that human beta(2)-AR gene was expressed in the cardiomyocytes infected by recombinant adenovirus contain cmv or mlc-2v promoter, but both is different.

Adenoviridae↗

PubMed2001

Potassium channel blocker TEA prevents CA1 hippocampal injury following transient forebrain ischemia in adult rats.

It has been recently reported that potassium channel increases activities in CA1 pyramidal neurons of rat hippocampus following transient forebrain ischemia. To understand the role of the enhanced potassium current in the pathogenesis of neuronal damage after ischemia, we examined the effects of tetraethylammonium (TEA) and 4-aminopyridine (4-AP) on the neuronal injury of CA1 region induced by 15 min forebrain ischemia using a four-vessel occlusion model. Adult rats received intracerebroventricular administration of either TEA or 4-AP after ischemia or TEA before ischemia and once each day for 7 days. In the postischemic TEA treated-rats, the neuronal injury in hippocampal CA1 region was significantly less than that of the controls. In contrast, neither preischemic infusion of TEA nor postischemic treatment of 4-AP had any neuroprotective effects. The present study demonstrates that postischemic application of TEA protects hippocampal CA1 pyramidal neurons against ischemic insult, suggesting that potassium channels may play important roles in the pathogenesis of CA1 neuronal death after transient forebrain ischemia.

4-Aminopyridine↗