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Biomedical subjects

B Xiao

Publications and source records attributed to B Xiao.

At least 19 recordsLinked to original sources

Inhibition of growth and increase of alkaline phosphatase activity in cultured human oral cancer cells by all-trans retinoic acid.

In this study, the effects of all-trans retinoic acid (ATRA) on human oral cancer cells with regard to cell growth, the cell cycle, and alkaline phosphatase (ALP) activity were evaluated. Human oral cancer KB cells were treated with various concentrations of ATRA, and cell growth was then determined using the MTT viability assay. The cell-cycle distribution and ALP activity were analysed using a flow cytometer and chemical analyser, respectively. The KB cells were inhibited by ATRA at concentrations of 1-16 microM (1 microM, P<0.05; 2 microM, P<0.01; 4, 8 and 16 microM, P<0.001) in a dose-dependent manner. ATRA arrested KB cells in the G0/G1 phase. The ALP activity in KB cells was increased by ATRA. This is one of the first studies to focus on the expression of ALP in human head-and-neck carcinoma cells treated with retinoids. These findings suggest that the anti-tumour effects of ATRA on human oral cancer are associated with G0/G1 phase arrest and an increase in ALP activity.

Alkaline Phosphatase↗

Hydrogen adsorption on functionalized nanoporous activated carbons.

There is considerable interest in hydrogen adsorption on carbon nanotubes and porous carbons as a method of storage for transport and related energy applications. This investigation has involved a systematic investigation of the role of functional groups and porous structure characteristics in determining the hydrogen adsorption characteristics of porous carbons. Suites of carbons were prepared with a wide range of nitrogen and oxygen contents and types of functional groups to investigate their effect on hydrogen adsorption. The porous structures of the carbons were characterized by nitrogen (77 K) and carbon dioxide (273 K) adsorption methods. Hydrogen adsorption isotherms were studied at 77 K and pressure up to 100 kPa. All the isotherms were Type I in the IUPAC classification scheme. Hydrogen isobars indicated that the adsorption of hydrogen is very temperature dependent with little or no hydrogen adsorption above 195 K. The isosteric enthalpies of adsorption at zero surface coverage were obtained using a virial equation, while the values at various surface coverages were obtained from the van't Hoff isochore. The values were in the range 3.9-5.2 kJ mol(-1) for the carbons studied. The thermodynamics of the adsorption process are discussed in relation to temperature limitations for hydrogen storage applications. The maximum amounts of hydrogen adsorbed correlated with the micropore volume obtained from extrapolation of the Dubinin-Radushkevich equation for carbon dioxide adsorption. Functional groups have a small detrimental effect on hydrogen adsorption, and this is related to decreased adsorbate-adsorbent and increased adsorbate-adsorbate interactions.

Journal Article↗

Adsorption of aqueous metal ions on oxygen and nitrogen functionalized nanoporous activated carbons.

In this study, the adsorption characteristics of two series of oxygen and nitrogen functionalized activated carbons were investigated. These series were a low nitrogen content (approximately 1 wt % daf) carbon series derived from coconut shell and a high nitrogen content (approximately 8 wt % daf) carbon series derived from polyacrylonitrile. In both series, the oxygen contents were varied over the range approximately 2-22 wt % daf. The porous structures of the functionalized activated carbons were characterized using N(2) (77 K) and CO(2) (273 K) adsorption. Only minor changes in the porous structure were observed in both series. This allowed the effect of changes in functional group concentrations on metal ion adsorption to be studied without major influences due to differences in porous structure characteristics. The surface group characteristics were examined by Fourier transform infrared (FTIR) spectroscopy, acid/base titrations, and measurement of the point of zero charge (pH(PZC)). The adsorption of aqueous metal ion species, M(2+)(aq), on acidic oxygen functional group sites mainly involves an ion exchange mechanism. The ratios of protons displaced to the amount of M(2+)(aq) metal species adsorbed have a linear relationship for the carbons with pH(PZC) < or = 4.15. Hydrolysis of metal species in solution may affect the adsorption of metal ion species and displacement of protons. In the case of basic carbons, both protons and metal ions are adsorbed on the carbons. The complex nature of competitive adsorption between the proton and metal ion species and the amphoteric character of carbon surfaces are discussed in relation to the mechanism of adsorption.

Journal Article↗

Reactions of nitrogen and oxygen surface groups in nanoporous carbons under inert and reducing atmospheres.

The reactions of surface functional groups have an important role in controlling conversion of char nitrogen to NOx during coal combustion. This study involved an investigation of the thermal stability and reactions of nitrogen surface functional groups in nanoporous carbons. Four suites of carbons, which were used as models for coal chars, were prepared with a wide range of nitrogen and oxygen contents and types of functional groups. The porous structures of the carbons were characterized by gas adsorption methods while chemical analysis, X-ray photoelectron spectroscopy, and X-ray near edge structure spectroscopy were used to characterize the surface functional groups. Temperature programmed desorption and temperature programmed reduction methods were used to study the reactivity of the surface functional groups during heat treatment under inert and reducing conditions. Heat treatment studies show that the order of stability of the functional groups is quaternary nitrogen > pyridinic > pyrrolic > pyridine N-oxide. Pyridine N-oxide surface groups desorb NO and form N2 via surface reactions at low temperature. Pyrrolic and pyridinic functional groups decompose and react with surface species to give NH3, HCN, and N2 as desorption products, but most pyrrolic groups are preferentially converted to pyridinic and quaternary nitrogen. The main desorption product is N2. Approximately 15-40 wt % of the original nitrogen was retained in the carbons mainly as quaternary nitrogen after heat treatment to 1673 K. The results are discussed in terms of decomposition ranges for surface functional groups and reaction mechanisms of surface species.

Journal Article↗

Clinical and genetic study on a new Chinese family with benign familial infantile seizures.

Three loci for benign familial infantile seizures (BFIS, traditionally named benign familial infantile convulsions) have been mapped to the chromosome regions of 19q12-13.1, 2q24, and 16p12-q12. We characterized the clinical features of a newly discovered Chinese family with BFIS and investigated whether it is linked to these loci. A four-generation Chinese family was investigated and nineteen family members were examined. Fourteen microsatellite markers covering the three BFIS loci on the chromosome regions of 19q12-13.1, 2q24, and 16p12-q12 were genotyped. Linkage analysis was performed. The main clinical features of our patients include onset of afebrile seizures between 3 and 10 months, normal psychomotor development, normal interictal electroencephalogram (EEG), and autosomal dominant inheritance. Magnetic resonance imaging (MRI) changes were found in the proband. Two-point LOD scores are < -2.0 at the recombination rate of 0.0 for all the markers on the 2q24 region. Multipoint LOD scores are < -3.0 for the regions of 19q12-13.1 and 16p12-q12. Linkage analysis showed no evidence that the disease gene of this BFIS family is linked to the chromosome regions previously identified as the critical regions of the disease. Another chromosome region harboring the disease gene may exist in the new Chinese family.

Adult↗

H1 and H7 influenza haemagglutinin structures extend a structural classification of haemagglutinin subtypes.

Comparing the structures of H3, H5 and H9 subtype haemagglutinins, we deduced a structural basis for including all 15 influenza subtypes in four clades. H3, H5 and H9 represent three of these clades; we now report the structure of an H7 HA as a representative of the fourth clade. We confirm the structure of the turn at the N-terminus of the conserved central alpha-helix of HA2, and the combination of ionisable residues near the "fusion peptide" as clade-specific features. We compare the structures of three H1 HAs with H5 HA in the same clade, to refine our previous classification and we confirm the division of the clades into two groups of two. We also show the roles of carbohydrate side chains in the esterase-fusion domain boundaries in the formation of clade-specific structural markers.

Amino Acid Sequence↗

Competitive adsorption of aqueous metal ions on an oxidized nanoporous activated carbon.

Competitive adsorption is the usual situation in real applications, and it is of critical importance in determining the overall performance of an adsorbent. In this study, the competitive adsorption characteristics of all the combinations of binary mixtures of aqueous metal ion species Ca2+(aq), Cd2+(aq), Pb2+(aq), and Hg2+(aq) on a functionalized activated carbon were investigated. The porous structure of the functionalized active carbon was characterized using N2 (77 K) and CO2 (273 K) adsorption. The surface group characteristics were examined by temperature-programmed desorption, Fourier transform infrared spectroscopy, Raman spectroscopy, acid/base titrations, and measurement of the point of zero charge (pHpzc). The adsorption of aqueous metal ion species, M2+(aq), on acidic oxygen functional group sites mainly involves an ion exchange mechanism. The ratios of protons displaced to the amount of M2+(aq) metal species adsorbed have a linear relationship for both single-ion and binary mixtures of these species. Hydrolysis of metal species in solution may affect the adsorption, and this is the case for adsorption of Hg2+(aq) and Pb2+(aq). Competitive adsorption decreases the amounts of individual metal ions adsorbed, but the maximum amounts adsorbed still follow the order Hg2+(aq) > Pb2+(aq) > Cd2+(aq) > Ca2+(aq) obtained for single metal ion adsorption. The adsorption isotherms for single metal ion species were used to develop a model for competitive adsorption in binary mixtures, involving exchange of ions in solution with surface proton sites and adsorbed metal ions, with the species having different accessibilities to the porous structure. The model was validated against the experimental data.

Journal Article↗

The structure and receptor binding properties of the 1918 influenza hemagglutinin.

The 1918 influenza pandemic resulted in about 20 million deaths. This enormous impact, coupled with renewed interest in emerging infections, makes characterization of the virus involved a priority. Receptor binding, the initial event in virus infection, is a major determinant of virus transmissibility that, for influenza viruses, is mediated by the hemagglutinin (HA) membrane glycoprotein. We have determined the crystal structures of the HA from the 1918 virus and two closely related HAs in complex with receptor analogs. They explain how the 1918 HA, while retaining receptor binding site amino acids characteristic of an avian precursor HA, is able to bind human receptors and how, as a consequence, the virus was able to spread in the human population.

Amino Acid Sequence↗

Multidrug-resistance-associated protein MGr1-Ag is identical to the human 37-kDa laminin receptor precursor.

We report the isolation and functional characterization of the gene encoding MGr1-Ag, a multidrug-resistance-associated protein. A lambdagt11 cDNA library derived from colorectal carcinoma SW480 cells was screened with monoclonal antibody MGr1. DNA homology analysis of 22 positive clones (designated R1-R22) suggested human 37-kDa laminin receptor precursor (37LRP, R7/R9/R15/R16/R19/R20) and a novel gene (R22) as candidate genes encoding MGr1-Ag. Western blot analysis showed that anti-R20 serum reacted with a unique protein band that was consistent with MGr1-Ag, while anti-R22 serum could not react with MGr1-Ag. The coding gene for MGr1-Ag was amplified using reverse transcription-PCR. Sequence analysis revealed that the MGr1-Ag and 37LRP genes shared the same coding sequence. An in vitro drug sensitivity assay indicated that down-regulation of 37LRP by an antisense technique could significantly enhance the cytotoxicity of anticancer drugs to gastric cancer cells. Thus we draw the conclusion that MGr1-Ag is identical to 37LRP.

Carcinoma↗

Kindling-induced overexpression of Homer 1A and its functional implications for epileptogenesis.

Despite an extensive research on the molecular basis of epilepsy, the essential players in the epileptogenic process leading to epilepsy are not known. Gene expression analysis is one strategy to enhance our understanding of the genes contributing to the functional neuronal changes underlying epileptogenesis. In the present study, we used the novel MPSS (massively parallel signature sequencing) method for analysis of gene expression in the rat kindling model of temporal lobe epilepsy. Kindling by repeated electrical stimulation of the amygdala resulted in the differential expression of 264 genes in the hippocampus compared to sham controls. The most strongly induced gene was Homer 1A, an immediate early gene involved in the modulation of glutamate receptor function. The overexpression of Homer 1A in the hippocampus of kindled rats was confirmed by RT-PCR. In order to evaluate the functional implications of Homer 1A overexpression for kindling, we used transgenic mice that permanently overexpress Homer 1A. Immunohistochemical characterization of these mice showed a marked Homer 1A overexpression in glutamatergic neurons of the hippocampus. Kindling of Homer 1A overexpressing mice resulted in a retardation of seizure generalization compared to wild-type controls. The data demonstrate that kindling-induced epileptogenesis leads to a striking overexpression of Homer 1A in the hippocampus, which may represent an intrinsic antiepileptogenic and anticonvulsant mechanism in the course of epileptogenesis that counteracts progression of the disease.

Animals↗

Adjuvant-induced arthritis: IL-1 beta, IL-6 and TNF-alpha are up-regulated in the spinal cord.

Adjuvant-induced arthritis (AIA) is a widely used animal model of human rheumatoid arthritis (RA). We have previously shown that increased neuropeptide expression is observed in the spinal cord of AIA rats. To study the potential role of cytokines in the spinal cord of AIA, we wanted to determine whether there are changes of glial and cytokine expression (IL-1 beta, IL-6, TNF-alpha and IFN-gamma) in the spinal cord of AIA rats. Our data indicated that macroglia and MHC class II immunostaining were enhanced, astrocytes expressing GFAP were increased in number and immunostaining intensity. Using in situ hybridization and immunohistochemical methods, both mRNA and protein levels of IL-1 beta, IL-6 and TNF-alpha were significantly increased in the spinal cord of arthritic rats. Increased cytokine expression was presented in the reactive astrocytes and microglia.

Animals↗

Unusual conformational changes in 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase as revealed by X-ray crystallography and NMR.

The crystal structure of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) in complex with MgADP has been determined at 1.5-A resolution with a crystallographic R factor of 0.191. The solution structure of HPPK in complex with Mg(2+) and beta,gamma-methyleneadenosine 5'-triphosphate (MgAMPPCP) has been determined using a simulated annealing protocol with 3,523 experimental NMR restraints. The root mean square deviation of the ensemble of 20 refined conformers that represent the solution structure from the mean coordinate set derived from them is 0.74 +/- 0.26 A for all backbone atoms and 0.49 +/- 0.22 A when residues Pro(14), Pro(44)-Gln(50), and Arg(84)-Pro(91) are excluded. Binding of MgADP causes significant changes in the conformation and dynamical property of three loops of HPPK that are involved in catalysis. A dramatic, unusual conformational change is that loop 3 moves away from the active center significantly with some residues moving by >17 A. The binding of MgADP also stabilizes loop 1 and loop 3 but makes loop 2 more mobile. Very similar conformational and dynamical changes are observed in the NMR solution structure of HPPK.MgAMPPCP. The conformational and dynamical changes may play important roles in both substrate binding and product release in the catalytic cycle.

Adenosine Diphosphate↗

[Study of delayed encephalopathy after acute carbon monoxide poisoning by clinical characteristic, CT and MRI features].

OBJECTIVE: To explore the diagnosis value of CT and MRI in delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). METHODS: The clinical, CT and MRI data of 20 patients with DEACMP were analysed. RESULTS: The main clinical manifestations of the disease were intellectual disturbances and personality disorders. CT scan in DEACMP showed that some characteristic changes (such as diffuse low density) was observed within bilateral cerebral white matter, prominently within bilateral or unilateral globus pallidus or basal ganglia areas. The MRI showed that brain lesions in DEACMP were bilateral symmetric punctate, spotty or confluent foci within periventricular white matter and centrum semioval, which showed high signal intensity in T2-weighted and low signal intensity in T1-weighted. The chronic ischemia changes were found in the globus pallidus or basal ganglia areas. Cerebral cortex lesions were observed occasionally. CONCLUSIONS: The diagnosis of DEACMP mainly depends on case history, clinical features and neuroradiological presence. MRI is more valuable in the diagnosis and the differential diagnosis than CT.

Adolescent↗

Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer.

G-protein-coupled receptors (GPCRs) transduce signals from extracellular transmitters to the inside of the cell by activating G proteins. Mutation and overexpression of these receptors have revealed that they can reach their active state even in the absence of agonist, as a result of a natural shift in the equilibrium between their inactive and active conformations. Such agonist-independent (constitutive) activity has been observed for the glutamate GPCRs (the metabotropic glutamate receptors mGluR1a and mGluR5) when they are overexpressed in heterologous cells. Here we show that in neurons, the constitutive activity of these receptors is controlled by Homer proteins, which bind directly to the receptors' carboxy-terminal intracellular domains. Disruption of this interaction by mutagenesis or antisense strategies, or expression of endogenous Homer1a (H1a), induces constitutive activity in mGluR1a or mGluR5. Our results show that these glutamate GPCRs can be directly activated by intracellular proteins as well as by agonists.

Animals↗

The structural basis of Arfaptin-mediated cross-talk between Rac and Arf signalling pathways.

Small G proteins are GTP-dependent molecular switches that regulate numerous cellular functions. They can be classified into homologous subfamilies that are broadly associated with specific biological processes. Cross-talk between small G-protein families has an important role in signalling, but the mechanism by which it occurs is poorly understood. The coordinated action of Arf and Rho family GTPases is required to regulate many cellular processes including lipid signalling, cell motility and Golgi function. Arfaptin is a ubiquitously expressed protein implicated in mediating cross-talk between Rac (a member of the Rho family) and Arf small GTPases. Here we show that Arfaptin binds specifically to GTP-bound Arf1 and Arf6, but binds to Rac.GTP and Rac.GDP with similar affinities. The X-ray structure of Arfaptin reveals an elongated, crescent-shaped dimer of three-helix coiled-coils. Structures of Arfaptin with Rac bound to either GDP or the slowly hydrolysable analogue GMPPNP show that the switch regions adopt similar conformations in both complexes. Our data highlight fundamental differences between the molecular mechanisms of Rho and Ras family signalling, and suggest a model of Arfaptin-mediated synergy between the Arf and Rho family signalling pathways.

ADP-Ribosylation Factor 1↗

Determination of sialic acids by liquid chromatography-mass spectrometry.

Sialic acids are widely found in nature as components of oligosaccharide units in mucins, glycoproteins and other microbial polymers. Existing methods for determining these acids are long, tedious, and not specific. A simple, rapid, and sensitive method for determining the most commonly occurring acids, N-acetylneuraminic and N-glycolylneuraminic acid, using LC-MS is described. Standard solutions of the sialic acids with the internal standard, N-acetylneuraminic acid methyl ester, were quantitatively analyzed by positive ion electrospray ionization. Fetuin was used as a model glycoprotein and the hydrolysate was injected directly onto an ES Industries AquaSep 3 microm 150x4.6 mm column eluted with a 0.1% aqueous formic acid mobile phase at a flow-rate of 0.5 ml/min. Detection was achieved using the Finnigan Navigator MS system in the selected ion monitoring mode for the protonated molecular ions at m/z 310, 324, and 326. The linearity over the dynamic range 10 to 1000 ng of sialic acids on-column had a correlation coefficient greater than 0.999. The amount of sialic acids found in the fetuin hydrolysate was in agreement with values reported in the literature.

Chromatography, Liquid↗