Biomedical subjects

M Zhou

Publications and source records attributed to M Zhou.

At least 37 records · Page 2Linked to original sources

PubMed2002

Detection of Fusarium head blight resistance QTL in a wheat population using bulked segregant analysis.

A population of 218 recombinant inbred lines (RILs) was developed from the cross of two wheat (Triticum aestivum L.) cultivars, 'Ning 894037' and 'Alondra'. Ning 894037 has resistance to Fusarium head blight (FHB) and Alondra is moderately susceptible. Response of the RILs and their parental lines to FHB infection was evaluated with point inoculation in four experiments both in greenhouse and in field conditions. Distribution of disease severity in the population is continuous, indicating quantitative inheritance of resistance to FHB. Bulked segregant analysis and QTL mapping based on simple sequence repeat (SSR) markers revealed three chromosome regions that are responsible for FHB resistance. A chromosome region on 3BS accounted for 42.5% of the phenotypic variation for FHB resistance. Additional QTLs were located on chromosomes 2D and 6B. These three QTLs jointly accounted for 51.6% of the phenotypic variation. SSR markers linked to the QTLs influencing resistance to FHB have potential for use in breeding programs.

Analysis of Variance↗

PubMed2002

Wide distribution of Plasmodium ovale in Myanmar.

The presence of Plasmodium ovale has never been previously reported in Myanmar. Using blood samples obtained in many villages across the country between 1996 and 2000, molecular diagnosis of Plasmodium species was made with semi- or full-nested polymerase chain reaction (PCR) with species-specific primers, followed by agarose gel electrophoresis to detect amplification products. The presence of P. ovale was also confirmed with the another PCR-based diagnosis, the microtiterplate hybridization (MPH) method using species-specific probes. Both methods target the A type of the small subunit ribosomal RNA gene of the four human malaria parasites. Plasmodium ovale DNA was amplified in samples from 65 (4.9%) of 1323 PCR-positive patients, with perfect agreement between results obtained by nested PCR and MPH. Only four P. ovale-infected patients had single-species infection; all others were coinfected with P. falciparum, P. vivax and/or P. malariae. Quadruple infections were observed in six subjects. Parasites with typical P. ovale morphology were found in only 19 patients by conventional microscopy of Giemsa-stained thin smears or fluorescence microscopy of acridine orange-stained thin smears. Plasmodium ovale infections were found in villages situated in the southern, central and western regions of Myanmar, suggesting that P. ovale may be widely distributed in this country.

Adolescent↗

PubMed2001

Friend of GATA-1 represses GATA-3-dependent activity in CD4+ T cells.

The development of naive CD4+ T cells into a T helper (Th) 2 subset capable of producing interleukin (IL)-4, IL-5, and IL-13 involves a signal transducer and activator of transcription (Stat)6-dependent induction of GATA-3 expression, followed by Stat6-independent GATA-3 autoactivation. The friend of GATA (FOG)-1 protein regulates GATA transcription factor activity in several stages of hematopoietic development including erythrocyte and megakaryocyte differentiation, but whether FOG-1 regulates GATA-3 in T cells is uncertain. We show that FOG-1 can repress GATA-3-dependent activation of the IL-5 promoter in T cells. Also, FOG-1 overexpression during primary activation of naive T cells inhibited Th2 development in CD4+ T cells. FOG-1 fully repressed GATA-3-dependent Th2 development and GATA-3 autoactivation, but not Stat6-dependent induction of GATA-3. FOG-1 overexpression repressed development of Th2 cells from naive T cells, but did not reverse the phenotype of fully committed Th2 cells. Thus, FOG-1 may be one factor capable of regulating the Th2 development.

Animals↗

PubMed2001

Activation of melatonin receptor increases a delayed rectifier K+ current in rat cerebellar granule cells.

The present study was initiated to investigate the effect of melatonin on K+ current in rat cerebellar granule cells for 2 to 6 days in culture (DIC). The whole-cell configuration of the conventional patch-clamp technique was used to record the outward K+ current. Two types of outward K+ current, a transient outward K+ current and a delayed rectifier K+ current, were separated by different voltage protocols and a specific blocker of K+ channel. Application of melatonin (10 microM) by a brief pressure ejection induced a significant and reversible increase of the delayed rectifier K+ current amplitude in 78% of the cells tested. The activated effect of melatonin on the K+ current was independent of the time in culture, and the percentage of activation remained at a relatively stable level from 2 DIC to 6 DIC; but that was dependent on the concentration of melatonin applied. The activation of the K+ current induced by melatonin presented no desensitization after repeated application of melatonin. The effect of melatonin on the K+ current can be mimicked by 2-iodomelatonin, a melatonin receptor agonist. With the addition of guanosine-5'-O-(3-thiophosphate) in the pipette solution, melatonin caused a stronger activation effect on the K+ channels, and an irreversible increase of the current amplitude in some granule cells tested. Pretreatment of cells with PTX suppressed the action of melatonin on the K+ current in most granule cells studied. In addition, the activation curves and inactivation curves tested with the steady-state activation and inactivation protocols were unchanged by melatonin, suggesting that melatonin did not modulate the channel's activation and inactivation properties. Our results demonstrated the presence of a functional melatonin receptor in cultured cerebellar granule cells from neonatal cerebellum. Activating the receptor can modulate the outward K+ currents by coupling to a PTX-sensitive G protein.

Animals↗

PubMed2001

Crystallization and preliminary crystallographic results of apo and complex forms of human dehydroepiandrosterone sulfotransferase.

Dehydroepiandrosterone sulfotransferase converts dehydroepiandrosterone (DHEA) and some other steroids to their sulfonated forms. The human enzyme has been crystallized in the presence of substrate (DHEA) alone, in the presence of substrate and non-sulfated cofactor analogue (PAP) and in the absence of both substrate and PAP in our laboratory, with data sets collected at a synchrotron source. The crystals of the uncomplexed form belong to the orthorhombic space group C222(1), with unit-cell parameters a = 85.26, b = 87.69, c = 108.20 A and data 99.2% complete to 2.35 A resolution. The DHEA complex crystallizes in the orthorhombic space group P2(1)2(1)2, with unit-cell parameters a = 74.46, b = 127.49, c = 44.59 A and data 92.9% complete to 2.15 A resolution. The ternary complex crystallizes in the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 62.25, b = 87.28, c = 138.86 A and data 98.6% complete to 2.50 A resolution. Preliminary molecular-replacement solutions indicate significant variations in dimer formation.

Apoenzymes↗

PubMed2001

Chromophore attachment to biliproteins: specificity of PecE/PecF, a lyase-isomerase for the photoactive 3(1)-cys-alpha 84-phycoviolobilin chromophore of phycoerythrocyanin.

PecE and PecF, the products of two phycoerythrocyanin lyase genes (pecE and pecF) of Mastigocladus laminosus (Fischerella), catalyze two reactions: (1) the regiospecific addition of phycocyanobilin (PCB) to Cys-alpha 84 of the phycoerythrocyanin alpha-subunit (PecA), and (2) the Delta 4-->Delta 2 isomerization of the PCB to the phycoviolobilin (PVB)-chromophore [Zhao et al. (2000) FEBS Lett. 469, 9-13]. The alpha-apoprotein (PecA) as well PecE and PecF were overexpressed from two strains of M. laminosus, with and without His-tags. The products of the spontaneous addition of PCB to PecA, and that of the reaction catalyzed by PecE/F, were characterized by their photochemistry and by absorption, fluorescence, circular dichroism of the four states obtained by irradiation with light (15-Z/E isomers of the chromophore) and/or modification of Cys-alpha 98/99 with thiol-directed reagents. The spontaneous addition leads to a 3(1)-Cys-PCB adduct, which is characteristic of allophycocyanins and phycocyanins, while the addition catalyzed by PecE and PecF leads to a 3(1)-Cys-PVB adduct which after purification was identical to alpha-PEC. The specificity and kinetics of the chromophore additions were investigated with respect to the structure of the bilin substrate: The 3-ethylidene-bilins, viz., PCB, its 18-vinyl analogue phytochromobilin, phycoerythrobilin and its dimethylester, react spontaneously to yield the conventional addition products (3-H, 3(1)-Cys), while the 3-vinyl-substituted bilins, viz., bilirubin and biliverdin, were inactive. Only phycocyanobilin and phytochromobilin are substrates to the addition-isomerization reaction catalyzed by PecE/F. The slow spontaneous addition of phycoerythrobilin is not influenced, and there is in particular no catalyzed isomerization to urobilin.

Amino Acid Sequence↗

PubMed2001

Freshly isolated hippocampal CA1 astrocytes comprise two populations differing in glutamate transporter and AMPA receptor expression.

We have shown previously that process-bearing GFAP+ astrocytes freshly isolated from rat hippocampus CA1 and CA3 regions are heterogeneous in ion channel expression and K(+) uptake capabilities, such that two distinct populations of astrocytes can be described (Zhou and Kimelberg, 2000). In the present study, we report that glutamate transporter (GT) currents can only be measured from one type of these freshly isolated hippocampal CA1 astrocytes [variably rectifying astrocytes (VRAs)] but were not detectable in the second type of astrocyte [outwardly rectifying astrocytes (ORAs)]. The GT currents showed a strict Na(+) dependency and high affinity for glutamate (EC(50) of 4 +/- 1.1 microm). The astrocytes lacking GT currents (ORAs) showed an AMPA receptor current density (55 pA/pF) that was 42-fold higher than VRAs (1.3 pA/pF). In contrast, the GABA(A) currents were of comparable current density in both types. The specificity of these differences makes it unlikely that they are attributable to preparative damage. Therefore, these findings strongly indicate that, within a single region of the hippocampus, GFAP+ astrocytes comprise a functionally diverse population that are qualitatively different in their functional glutamate transporter and quantitatively different in their functional AMPA receptor expression. This heterogeneity implies that GFAP+ astrocytes may participate in or modulate glutamate synaptic transmission differently.

ATP-Binding Cassette Transporters↗

PubMed2001

A combined theoretical and experimental study of the reaction products of laser-ablated thorium atoms with CO: first identification of the CThO, CThO(-), OthCCO, OTh(eta(3)-CCO), and Th(CO)(n) (n = 1-6) molecules.

Laser-ablated thorium atoms have been reacted with CO molecules during condensation in excess neon. Absorptions at 617.7 and 812.2 cm(-1) are assigned to Th-C and Th-O stretching vibrations of the CThO molecule. Absorptions at 2048.6, 1353.6, and 822.5 cm(-1) are assigned to the OThCCO molecule, which is formed by CO addition to CThO and photochemical rearrangement of Th(CO)(2). The OThCCO molecule undergoes further photoinduced rearrangement to OTh(eta(3)-CCO), which is characterized by C-C, C-O, and Th-O stretching vibrations at 1810.8, 1139.2, and 831.6 cm(-1). The Th(CO)(n) (n = 1-6) complexes are formed on deposition or on annealing. Evidence is also presented for the CThO(-) and Th(CO)(2)(-) anions, which are formed by electron capture of neutral molecules. Relativistic density functional theory (DFT) calculations of the geometry structures, vibrational frequencies, and infrared intensities strongly support the experimental assignments. It is found that CThO is an unprecedented actinide-containing carbene molecule with a triplet ground state and an unusual bent structure ( angleCThO = 109 degrees ). The OThCCO molecule has a bent structure while its rearranged product OTh(eta(3)-CCO) is found to have a unique exocyclic structure with side-bonded CCO group. We also find that both Th(CO)(2) and Th(CO)(2)(-) are, surprisingly, highly bent, with the angleC-Th-C bond angle being close to 50 degrees; the unusual geometries are the result of extremely strong Th-to-CO back-bonding, which causes significant three-centered bonding among the Th atom and the two C atoms.

Journal Article↗

PubMed2001

The role of lipopolysaccharide in stimulating adrenomedullin production during polymicrobial sepsis.

Previous studies have shown that adrenomedullin (AM), a potent vasodilatory peptide, is upregulated during sepsis. However, it remains unknown whether the increased AM observed under such conditions is solely due to the elevated levels of circulating lipopolysaccharide (LPS). To determine this, an Alzet micro-osmotic pump, containing a low dose of Escherichia coli LPS or vehicle (sterile normal saline), was implanted in the peritoneal cavity of the normal male adult rat. At 10 h after the pump implantation, samples of blood and small intestine were harvested for the determination of AM by radioimmunoassay. In additional groups, rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). LPS binding agent polymyxin B was administrated intramuscularly at 1 h prior to as well as 5 h after the onset of sepsis. At 10 h after CLP or sham-operation, blood and intestinal samples were harvested and levels of AM were then determined. Plasma levels of LPS were also measured by Limulus amebocyte lysate assay. The results indicate that administration of a low dose of LPS via the peritoneal cavity in normal animals (which did not significantly alter cardiac output, blood pressure or heart rate) markedly increased plasma and intestinal levels of AM. In addition, plasma and tissue levels of AM increased significantly at 10 h after CLP. Administration of polymyxin B, however, attenuated the increase in AM levels under such conditions. Similarly, the increased plasma levels of LPS was significantly reduced by polymyxin B during sepsis. These results, taken together, suggest that the upregulated AM observed during polymicrobial sepsis is at least in part due to the increase in circulating levels of endotoxin.

Adrenomedullin↗

PubMed2001

TFIIH inhibits CDK9 phosphorylation during human immunodeficiency virus type 1 transcription.

Tat stimulates human immunodeficiency virus, type 1 (HIV-1), transcription elongation by recruitment of the human transcription elongation factor P-TEFb, consisting of CDK9 and cyclin T1, to the TAR RNA structure. It has been demonstrated further that CDK9 phosphorylation is required for high affinity binding of Tat/P-TEFb to the TAR RNA structure and that the state of P-TEFb phosphorylation may regulate Tat transactivation. We now demonstrate that CDK9 phosphorylation is uniquely regulated in the HIV-1 preinitiation and elongation complexes. The presence of TFIIH in the HIV-1 preinitiation complex inhibits CDK9 phosphorylation. As TFIIH is released from the elongation complex between +14 and +36, CDK9 phosphorylation is observed. In contrast to the activity in the "soluble" complex, phosphorylation of CDK9 is increased by the presence of Tat in the transcription complexes. Consistent with these observations, we have demonstrated that purified TFIIH directly inhibits CDK9 autophosphorylation. By using recombinant TFIIH subcomplexes, our results suggest that the XPB subunit of TFIIH is responsible for this inhibition of CDK9 phosphorylation. Interestingly, our results further suggest that the phosphorylated form of CDK9 is the active kinase for RNA polymerase II carboxyl-terminal domain phosphorylation.

Blotting, Western↗

PubMed2001

Crystal structure of Bruton's tyrosine kinase domain suggests a novel pathway for activation and provides insights into the molecular basis of X-linked agammaglobulinemia.

Bruton's tyrosine kinase is intimately involved in signal transduction pathways regulating survival, activation, proliferation, and differentiation of B lineage lymphoid cells. Mutations in the human btk gene are the cause of X-linked agammaglobulinemia, a male immune deficiency disorder characterized by a lack of mature, immunoglobulin-producing B lymphocytes. We have determined the x-ray crystal structure of the Bruton's tyrosine kinase kinase domain in its unphosphorylated state to a 2.1 A resolution. A comparison with the structures of other tyrosine kinases and a possible mechanism of activation unique to Bruton's tyrosine kinase are provided.

Agammaglobulinaemia Tyrosine Kinase↗

PubMed2001

The role of Kupffer cell alpha(2)-adrenoceptors in norepinephrine-induced TNF-alpha production.

Although previous studies have demonstrated that plasma levels of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) increase during early sepsis, the precise mechanism responsible for its upregulation remains to be elucidated. Since recent studies have shown that the gut is an important source of norepinephrine (NE) release during early sepsis and enterectomy prior to the onset of sepsis attenuates TNF-alpha production, we hypothesized that gut-derived NE plays a major role in upregulating TNF-alpha via the activation of alpha(2)-adrenoceptors on Kupffer cells. To confirm that NE increases TNF-alpha synthesis and release, Kupffer cells were isolated from normal rats and incubated with NE (20 or 50 nM) or another alpha(2)-adrenergic agonist clonidine (50 nM) without addition of Escherichia coli endotoxin. Supernatant levels of TNF-alpha were then measured. In additional animals, intraportal infusion of NE (20 microM) with or without the specific alpha(2)-adrenergic antagonist yohimbine (1 mM) at a rate of 13 microl/min was carried out for 2 h. Plasma and Kupffer cell levels of TNF-alpha were assayed thereafter. Moreover, the effects of NE and yohimbine on TNF-alpha production was further examined using an isolated perfused liver preparation. The results indicate that both NE and clonidine increased TNF-alpha release by approximately 4-7-fold in the isolated cultured Kupffer cells. Similarly, intraportal infusion of NE in vivo or in isolated livers increased TNF-alpha synthesis and release which was inhibited by co-infusion of yohimbine. Furthermore, the increased cellular levels of TNF-alpha in Kupffer cells after in vivo administration of NE was also blocked by yohimbine. These results, taken together, suggest that gut-derived NE upregulates TNF-alpha production in Kupffer cells through an alpha(2)-adrenergic pathway, which appears to be responsible at least in part for the increased levels of circulating TNF-alpha observed during early sepsis as well as other pathophysiologic conditions such as trauma, hemorrhagic shock, or gut ischemia/reperfusion.

Adrenergic alpha-Agonists↗

PubMed2001

Lyn is required for normal stem cell factor-induced proliferation and chemotaxis of primary hematopoietic cells.

Stem cell factor (SCF) binds to c-Kit and is an important mediator of survival, growth, and function of hematopoietic progenitor cells and mast cells. Lyn and other Src family members are activated by SCF and associate with phosphorylated tyrosine residues in the c-Kit juxtamembrane region. However, studies using c-Kit mutants incapable of directly recruiting Src family members suggest this kinase family plays a minimal role in c-Kit stimulus-response coupling mechanisms. The objective of this study was to specifically target Lyn and subsequently address its role in SCF-mediated responses of primary hematopoietic progenitor cells and mast cells. To this end, a dominant-inhibitory Lyn mutant and Lyn-deficient mice were used. Transfection of normal murine mast cells with kinase-inactive Lyn impaired SCF-induced growth. Further, SCF-induced proliferation and chemotaxis of Lyn-deficient mast cells were less than for wild-type mast cells. SCF-induced growth of progenitor cells lacking Lyn was also reduced compared with that of wild-type progenitor cells. Impairment of SCF-mediated responses of Lyn-deficient mast cells and progenitor cells did not result from reductions in surface expression of c-Kit. These studies demonstrate that Lyn is required for normal SCF-mediated responses of primary progenitors and for a differentiated lineage.

Animals↗

PubMed2001

Partial degradation of phenol by advanced electrochemical oxidation process.

The partial electrocatalytic degradation of phenol to organic acids has been investigated using an undivided electrolytic reactor with a beta-PbO2 anode containing fluorine resin. It was found that the decrease of benzoquinone (BQ) formed during phenol degradation and the acceleration of the process from phenol to organic acids are possible under an optimized operating condition. A possible pathway for phenol degradation was proposed, and a mathematical model for phenol and BQ evolution was developed. Operating parameters such as initial pH, current density, and temperature of the reaction were found to greatly impact the degradation rate of the phenol and even the pathway. Higher removal rate of phenol and BQ can be achieved at an appropriate temperature and higher current density in acidic medium preferably at pH 4. Under these conditions, phenol would be more likely degraded in the pathway from phenol to organic acids rather than through the BQ. When phenol is completely removed, the toxicity of the wastewater would be lessened suitable for biological process treatment. Accounting for the decrease of instantaneous current efficiency (ICE) during degradation, partial degradation would be highly economical for wastewater treatment, which would be an alternative process in practical application.

Disinfectants↗

PubMed2001

[Effects of losartan on renal ultrastructure in diabetic rats].

OBJECTIVE: To observe the effects of losartan on renal ultrastructure in streptozotocin diabetic rats. METHODS: Male SD rats were randomly divided into 2 groups: normal control group (NC group) and diabetic group. Diabetic group was induced by streptozocin (65 mg.kg-1) abdominal injection. Four weeks later, diabetic rats were further divided into 2 groups: diabetic rats treated with losartan (DL group, 20 mg.kg-1.d-1, by gavage) and diabetic unteated control group (DC group). Renal ultrastructure of each group was observed before and after 12 weeks of treatment respectively. RESULTS: The ultrastructure alterations in DL group including mesangial expansion and thickening of glomerular basement membrane (GBM), were lighter than those in DC group. CONCLUSION: Losartan can prevent renal pathological progress in diabetic rats. It is suggested that losartan may have some renal protective effects.

Animals↗

PubMed2001

[Clinical study of the effect of buflomedil on peripheral neuropathy in diabetic patients].

OBJECTIVE: To observe the effect of buflomedil on clinical symptom and nerve conduction velocity (NCV) of diabetic peripheral neuropathy patients. METHODS: 58 cases of diabetic patents with peripheral neuropathy were divided into diabetes group treated with buflomedil (DB) 100 mg.d-1 and diabetes control group (DP) treated with PGE1 200 micrograms.d-1. NCV was measured and peripheral nerve symtom was observed in two groups before treatment and after 2 weeks. RESULTS: NCV and peripheral nerve symptom were obviously improved both in DB group and DP group (P < 0.01). The effective rate were respectively 80.0% and 89.3% in DB group and DP group. The diversity was no significant in DB group and DP group (P > 0.05). CONCLUSION: buflomedil is an effective and safe drug for treating diabetic peripheral neuropathy patients.

Adrenergic alpha-Antagonists↗

PubMed2001

Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors.

Many voltage-dependent K+ channels open when the membrane is depolarized and then rapidly close by a process called inactivation. Neurons use inactivating K+ channels to modulate their firing frequency. In Shaker-type K+ channels, the inactivation gate, which is responsible for the closing of the channel, is formed by the channel's cytoplasmic amino terminus. Here we show that the central cavity and inner pore of the K+ channel form the receptor site for both the inactivation gate and small-molecule inhibitors. We propose that inactivation occurs by a sequential reaction in which the gate binds initially to the cytoplasmic channel surface and then enters the pore as an extended peptide. This mechanism accounts for the functional properties of K+ channel inactivation and indicates that the cavity may be the site of action for certain drugs that alter cation channel function.

Amines↗

PubMed2001

Resting murine neutrophils express functional alpha 4 integrins that signal through Src family kinases.

There is mounting evidence that alpha(4) (CD49d) integrins are involved in neutrophil recruitment and function during inflammatory responses. We report that all resting murine neutrophils derived from bone marrow or peripheral blood express easily detectable levels of alpha(4) integrins on their surface. These alpha(4) integrins were functional, as demonstrated by stimulation of respiratory burst when neutrophils adhered to surfaces coated with the murine vascular cell adhesion molecule-1 (mVCAM-1). Adhesion occurred via alpha(4) integrins, as preincubation of neutrophils with an anti-alpha(4)-specific Ab inhibited attachment to mVCAM-1. Direct cross-linking of the alpha(4) integrin subunit by surface-bound mAbs also elicited superoxide release and release of the secondary granule marker, lactoferrin. The functional responses that occurred downstream of alpha(4) integrin cross-linking required signaling by Src family kinases. Neutrophils derived from hck(-/-)fgr(-/-)lyn(-/-) triple-knockout or hck(-/-)fgr(-/-) double-knockout mice failed to undergo respiratory burst when plated on mVCAM-1. Triple mutant neutrophils were also defective in release of both superoxide and lactoferrin when plated on surfaces coated with mAbs directed against alpha(4). Correlated with impaired alpha(4)-induced functional responses, triple-mutant neutrophils also failed to spread and tightly adhere to anti-alpha(4) mAb-coated surfaces. This is the first direct evidence that functional alpha(4) integrins are expressed by murine PMNs, and that these surface molecules can mediate cellular responses such as tight adhesion, spreading, sustained respiratory burst, and specific granule release in vitro. Moreover the alpha(4) integrins, like all other integrins tested, use the Src family kinases to transduce intracellular signals.

Animals↗