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Biomedical subjects

X Z Xu

Publications and source records attributed to X Z Xu.

At least 19 recordsLinked to original sources
PubMed2005

Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase.

The antioncogenic Chk2 kinase plays a crucial role in DNA damage-induced cell-cycle checkpoint regulation. Here we show that Chk2 associates with the oncogenic protein Wip1 (wild-type p53-inducible phosphatase 1) (PPM1D), a p53-inducible protein phosphatase. Phosphorylation of Chk2 at threonine68 (Thr68), a critical event for Chk2 activation, which is normally induced by DNA damage or overexpression of Chk2, is inhibited by expression of wild-type (WT), but not a phosphatase-deficient mutant (D314A) of Wip1 in cultured cells. Furthermore, an in vitro phosphatase assay revealed that Wip1 (WT), but not Wip1 (D314A), dephosphorylates Thr68 on phosphorylated Chk2 in vitro, resulting in the inhibition of Chk2 kinase activity toward glutathione S-transferase-Cdc25C. Moreover, inhibition of Wip1 expression by RNA interference results in abnormally sustained Thr68 phosphorylation of Chk2 and increased susceptibility of cells in response to DNA damage, indicating that Wip1 acts as a negative regulator of Chk2 in response to DNA damage.

Amino Acids↗
PubMed2001

RETRACTED: Field-induced superconductivity in a spin-ladder cuprate.

We report on the modulation of the transport properties of thin films, grown by molecular beam epitaxy, of the spin-ladder compound [CaCu2O3]4, using the field effect in a gated structure. At high hole-doping levels, superconductivity is induced in the nominally insulating ladder material without the use of high-pressure or chemical substitution. The observation of superconductivity is in agreement with the theoretical prediction that holes doped into spin ladders could pair and possibly superconduct.

Journal Article↗
PubMed2001

Regulation of melastatin, a TRP-related protein, through interaction with a cytoplasmic isoform.

The TRP (transient receptor potential) superfamily includes a group of subfamilies of channel-like proteins mediating a multitude of physiological signaling processes. The TRP-melastatin (TRPM) subfamily includes the putative tumor suppressor melastatin (MLSN) and is a poorly characterized group of TRP-related proteins. Here, we describe the identification and characterization of an additional TRPM protein TRPM4. We reveal that TRPM4 and MLSN each mediate Ca(2+) entry when expressed in HEK293 cells. Furthermore, we demonstrate that a short form of MLSN (MLSN-S) interacts directly with and suppresses the activity of full-length MLSN (MLSN-L). This suppression seems to result from the inhibition of translocation of MLSN-L to the plasma membrane. We propose that control of translocation through interaction between MLSN-S and MLSN-L represents a mode for regulating ion channel activity.

Amino Acid Sequence↗
PubMed2001

Reconstruction of ureteral defects with microvascular vein grafts in a rat model.

This study was undertaken to test the performance of an autologous vein graft as a ureteral replacement in the rat model. Twenty-six rats were divided into three groups. In Group 1 (n = 10), the animals had a 3-mm segment of the ipsilateral ureter excised and the ureteral defect repaired, using a superficial epigastric vein graft. In Group 2 (n = 10), the same ureteral defect was created and again repaired, using a superficial epigastric vein graft, with the addition of a Silastic stent. The control, Group 3 (n = 6), had the ureter transected and repaired solely by means of primary anastomosis. Animals from each group underwent urography and were sacrificed for histology at three different postoperative intervals: 1, 4, and 12 weeks. Postoperative urography results showed normal renal function in the animals with ureteral reconstruction using vein grafting aided by a stent, as well as in those with primary ureteral anastomosis. No renal function return was seen in the animals with ureteral reconstruction by vein grafting alone, without stent support. Histologically, a progressive loss of the vascular endothelium, and replacement with the urothelium typical of the ureter, was seen in the stented vein grafts. Severe ureteral obstruction at the proximal site of the graft and hydronephrosis were seen in the vein-graft group without stenting. This study demonstrates that autologous vein grafts can be used successfully to correct a ureteral deficit, contingent on accurate microsurgical technique and immediate stenting.

Anastomosis, Surgical↗
PubMed2000

Free vascularized fibular bone flap in the rat.

Free vascularized fibula bone flap has been widely used in reconstruction of the mandible, long segment defect, congenital pseudarthroses, and osteomyelitis. Such applications stirred an interest in basic studies of bone biology, bone healing process, and incorporation of recipient bone defect. An experimental free vascularized fibula rat model is presented here for such investigations. We performed 16 angiograms and anatomic dissections in eight rats for collecting data on fibular length, blood supply, and the caliber of significant vessels. The fibula was harvested with part of the flexor hallucis longus muscle with an average length of 28 mm. The pedicle can be taken in continuity with the popliteal vessels (average diameter of 0.8 mm and 0.9 mm of artery and vein, respectively, with an average pedicle length of 14 mm). This vascularized fibula bone was harvested and transferred to the groin area of the same rat and anastomosed to the saphenous vessels. Twelve transplantations were performed, with a 7-day flap survival rate of 100%. The free fibula vascularized bone flap in the rat is a reliable model for further investigations.

Animals↗
PubMed2000

TRPgamma, a drosophila TRP-related subunit, forms a regulated cation channel with TRPL.

TRP and TRPL are two light-sensitive cation channel subunits required for the Drosophila photoresponse; however, our understanding of the identities, subunit composition, and function of the light-responsive channels is incomplete. To explain the residual photoresponse that remains in the trp mutant, a third TRP-related subunit has previously been proposed to function with TRPL. Here, we identify such a subunit, TRPgamma. We show that TRPgamma is highly enriched in photoreceptor cells and preferentially heteromultimerizes with TRPL in vitro and in vivo. The N-terminal domain of TRPgamma dominantly suppressed the TRPL-dependent photoresponse, indicating that TRPgamma-TRPL heteromultimers contribute to the photoresponse. While TRPL and TRPgamma homomultimers are constitutively active, we demonstrate that TRPL-TRPgamma heteromultimers form a regulated phospholipase C- (PLC-) stimulated channel.

Amino Acid Sequence↗
PubMed2000

[Studies on chemical components of Gentiana tizuensis Franch. (I)].

OBJECTIVE: To study the chemical components of Gentiana tizuensis distributed in Qinghai Province. METHOD: Chromatography and spectral analyses were used to isolate the constituents and elucidate their structure. RESULT: Four compounds were isolated and identified as uvaol, L-(+)-l-O-methyl-myo-inositol, ursolic acid,beta-sitosterol. CONCLUSION: All these components were obtained from the plant for the first time.

Gentiana↗
PubMed1999

Activation of a TRPC3-dependent cation current through the neurotrophin BDNF.

Nonvoltage-gated cation currents, which are activated following stimulation of phospholipase C (PLC), appear to be major modes for Ca2+ and Na+ entry in mammalian cells. The TRPC channels may mediate some of these conductances since their expression in vitro leads to PLC-dependent cation influx. We found that the TRPC3 protein was highly enriched in neurons of the central nervous system (CNS). The temporal and spatial distribution of TRPC3 paralleled that of the neurotrophin receptor TrkB. Activation of TrkB by brain-derived nerve growth factor (BDNF) led to production of a PLC-dependent, nonselective cation conductance in pontine neurons. Evidence is provided that TRPC3 contributes to this current in vivo. Thus, activation of TrkB and PLC leads to a TRPC3-dependent cation influx in CNS neurons.

Animals↗
PubMed1999

Termination of phototransduction requires binding of the NINAC myosin III and the PDZ protein INAD.

Many of the proteins that are critical for Drosophila phototransduction assemble into a signaling complex, signalplex, through association with the PDZ-domain protein INAD. Some of these proteins depend on INAD for proper subcellular localization to the phototransducing organelle, the rhabdomere, making it difficult to assess any physiological function of this signaling complex independent of localization. Here we demonstrated that INAD bound directly to the NINAC myosin III, yet the subcellular localization of NINAC was normal in inaD mutants. Nevertheless, the INAD binding site was sufficient to target a heterologous protein to the rhabdomeres. Disruption of the NINAC/INAD interaction delayed termination of the photoreceptor response. Thus one role of this signaling complex is in rapid deactivation of the photoresponse.

Animals↗
PubMed1998

Retinal targets for calmodulin include proteins implicated in synaptic transmission.

Ca2+ influxes regulate multiple events in photoreceptor cells including phototransduction and synaptic transmission. An important Ca2+ sensor in Drosophila vision appears to be calmodulin since a reduction in levels of retinal calmodulin causes defects in adaptation and termination of the photoresponse. These functions of calmodulin appear to be mediated, at least in part, by four previously identified calmodulin-binding proteins: the TRP and TRPL ion channels, NINAC and INAD. To identify additional calmodulin-binding proteins that may function in phototransduction and/or synaptic transmission, we conducted a screen for retinal calmodulin-binding proteins. We found eight additional calmodulin-binding proteins that were expressed in the Drosophila retina. These included six targets that were related to proteins implicated in synaptic transmission. Among these six were a homolog of the diacylglycerol-binding protein, UNC13, and a protein, CRAG, related to Rab3 GTPase exchange proteins. Two other calmodulin-binding proteins included Pollux, a protein with similarity to a portion of a yeast Rab GTPase activating protein, and Calossin, an enormous protein of unknown function conserved throughout animal phylogeny. Thus, it appears that calmodulin functions as a Ca2+ sensor for a broad diversity of retinal proteins, some of which are implicated in synaptic transmission.

Amino Acid Sequence↗
PubMed1998

Coordination of an array of signaling proteins through homo- and heteromeric interactions between PDZ domains and target proteins.

The rapid activation and feedback regulation of many G protein signaling cascades raises the possibility that the critical signaling proteins may be tightly coupled. Previous studies show that the PDZ domain containing protein INAD, which functions in Drosophila vision, coordinates a signaling complex by binding directly to the light-sensitive ion channel, TRP, and to phospholipase C (PLC). The INAD signaling complex also includes rhodopsin, protein kinase C (PKC), and calmodulin, though it is not known whether these proteins bind to INAD. In the current work, we show that rhodopsin, calmodulin, and PKC associate with the signaling complex by direct binding to INAD. We also found that a second ion channel, TRPL, bound to INAD. Thus, most of the proteins involved directly in phototransduction appear to bind to INAD. Furthermore, we found that INAD formed homopolymers and the homomultimerization occurred through two PDZ domains. Thus, we propose that the INAD supramolecular complex is a higher order signaling web consisting of an extended network of INAD molecules through which a G protein-coupled cascade is tethered.

Animals↗
PubMed1998

[Dye coupling between visual cortical (area 17) neurones of adult rat--a study on brain slices].

With intracellular injection of biocytin, forty-nine neurones were successfully labeled in in vitro visual cortex (area 17) slices of the adult rat. Out of the sample dye coupling was found in 21 cases, for each injection the number of the coupled cells varying from 2 to 5 (mean 2.8 +/- 1.1). Eighteen couplings were pyramidal-pyramidal, two were pyramidal-nonpyramidal, and one was seen among non-pyramidal cells. In most cases, the coupled cells were apart from each other with a certain distance among their cell bodies (mean 43.1 +/- 24 microns). The longest distance was up to 635 microns. Most couplings (19/21) were observed within the same lamina; only two in different laminae. The dye couplings were found in laminae II/III, IV and V, but mostly in laminae II/III. We have measured membrane potential and response properties to white matter and intracellular stimulation for the coupled and non-coupled cells; no significant difference was found between them.

Animals↗
PubMed1997

Coassembly of TRP and TRPL produces a distinct store-operated conductance.

The Drosophila retinal-specific protein, TRP (transient receptor potential), is the founding member of a family of store-operated channels (SOCs) conserved from C. elegans to humans. In vitro studies indicate that TRP is a SOC, but that the related retinal protein, TRPL, is constitutively active. In the current work, we report that coexpression of TRP and TRPL leads to a store-operated, outwardly rectifying current distinct from that owing to either TRP or TRPL alone. TRP and TRPL interact directly, indicating that the TRP-TRPL-dependent current is mediated by heteromultimeric association between the two subunits. We propose that the light-activated current in photoreceptor cells is produced by a combination of TRP homo- and TRP-TRPL heteromultimers.

Animals↗
PubMed1996

Autoprocessing: an essential step for the activation of HIV-1 protease.

Human immunodeficiency virus type 1 (HIV-1) expresses its structural and functional proteins within Gag-Pol precursor polyproteins. Specific proteolytic processing of the precursors by the viral protease is critical for the maturation and infectivity of viral particles. To observe the influence of autoprocessing on the activation of recombinant HIV-1 protease, we constructed different HIV-1 protease forms, with or without the Phe-Pro bond directly upstream of the protease domain, and expressed them in Escherichia coli systems. We found that the presence of a short upstream sequence of the protease domain, which could generate the original N-terminus of the protease by autoproteolysis of the Phe-Pro bond, resulted in processing of active protease, whereas for a wild-type protease extended only with the initiator methionine, the proteolytic activity was not recovered. Our results suggested that autoprocessing of the direct upstream sequence of the protease domain is an essential step for the activation of recombinant HIV-1 protease in the E. coli expression system. Expression of HIV-1 protease as fusion proteins revealed that the existence of a fusion portion increased the accumulation of expressed protease by affecting its homotypic dimer formation.

Base Sequence↗
PubMed1995

A simple and comprehensive method for the construction, repair and recycling of single and double tungsten microelectrodes.

A method for the construction, repair and recycling of tungsten-in-glass micro-electrodes is described. Essentially, the method employs insulating tungsten electrodes by collapsing borosilicate-glass capillaries onto tungsten wires. Procedures are described for either (1) removing excess glass insulation from the microelectrode tip or (2) fine adjustment and reshaping of the exposed electrode tip. This approach enables the controlled shaping of the electrode tip during preparation and/or reshaping the electrode tip or glass insulation of damaged electrodes. The method may be applied in the preparation of bipolar tungsten-in-glass electrode and tungsten electrode/micropipette assemblies. Advantages of the method are discussed.

Electrophysiology↗
PubMed1994

Hypoxia-selective antitumor agents. 9. Structure-activity relationships for hypoxia-selective cytotoxicity among analogues of 5-[N,N-bis(2-chloroethyl)amino]-2,4-dinitrobenzamide.

A series of analogues of the novel hypoxia-selective cytotoxin 5-[N,N-bis(2-chloroethyl)amino]-2,4-dinitrobenzamide (6) have been prepared and evaluated, in a search for compounds which retain high hypoxic selectivity but have increased potency and/or aqueous solubility. Several analogues with ionizable or dipolar carboxamide side chains showed improved solubility but generally had reduced cytotoxic potency and hypoxic selectivity. Modification of the mustard leaving groups or replacement of the carboxamide moiety provided some compounds with superior potency, but only the mixed chloro/mesylate mustard 20 provided a gain in potency relative to solubility while retaining the hypoxic selectivity of 6. These nitrogen mustards did not show the remarkable activity demonstrated by the related aziridine 7 [CB 1954, 5-(N-aziridinyl)- 2,4-dinitrobenzamide] in Walker 256 adenocarcinoma cells and are not efficient substrates for the DT-diaphorase which activates the latter compound by aerobic nitroreduction in Walker cells. Variations in hypoxic selectivity within the dinitrobenzamide mustards appear not to be due to differences in sensitivity to activation by this enzyme. Walker cells showed intermediate sensitivity to the mono(2-chloroethyl) analogue 26 but not to the related half-mustard 27, suggesting that the inhibition of DT-diaphorase activity is due to steric effects in the 5-position. The preferred compound overall with respect to solubility, potency, and in vitro hypoxic cell selectivity was the (dimethylamino)-ethyl derivative 11. DNA elution studies and comparison of the sensitivity of AA8 and UV4 cells to this compound indicated reductive activation to form a DNA cross-linking agent under hypoxia. Radiobiological studies indicated 11 to be equally active against both aerobic and hypoxic cells in KHT tumors. It is not clear whether this reflects efficient killing of aerobic cells as a result of diffusion of reduced metabolites from hypoxic regions or whether cytotoxicity in tumors is independent of hypoxia.

Aniline Mustard↗
PubMed1993

A study of siliceous pneumoconiosis in a desert area of Sunan County, Gansu Province, China.

Three hundred and ninety five residents in a desert area were examined with chest radiographs and 28 cases with siliceous pneumoconiosis were found. The prevalence of siliceous pneumoconiosis was 7.09%, and that over 40 years of age was 21%. The histological findings of lungs from a camel living in that area for 20 years also confirmed to have siliceous pneumoconiosis.

Adult↗