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Biomedical subjects

J Bai

Publications and source records attributed to J Bai.

At least 55 records · Page 3Linked to original sources

Pathogen fitness penalty as a predictor of durability of disease resistance genes.

Host plant resistance has been used extensively for disease control in many crop species; however, the resistance conferred by many sources is not durable as a result of rapid changes in the pathogen. Although many resistance genes have been identified in plant germplasm, there is no easy way to predict the quality or durability of these resistance genes. In this review, we revisit the hypothesis that resistance genes imposing a high penalty to the pathogen for adaptation will likely be durable. By elucidating the molecular changes involved in pathogen adaptation and the associated fitness cost, a proactive approach may be developed to predict the durability of resistance genes available for deployment.

Bacteria↗

The cell adhesion molecule Echinoid defines a new pathway that antagonizes the Drosophila EGF receptor signaling pathway.

Photoreceptor and cone cells in the Drosophila eye are recruited following activation of the epidermal growth factor receptor (EGFR) pathway. We have identified echinoid (ed) as a novel putative cell adhesion molecule that negatively regulates EGFR signaling. The ed mutant phenotype is associated with extra photoreceptor and cone cells. Conversely, ectopic expression of ed in the eye leads to a reduction in the number of photoreceptor cells. ed expression is independent of EGFR signaling and ED is localized to the plasma membrane of every cells throughout the eye disc. We present evidence that ed acts nonautonomously to generate extra R7 cells by a mechanism that is sina-independent but upstream of Tramtrack (TTK88). Together, our results support a model whereby ED defines an independent pathway that antagonizes EGFR signaling by regulating the activity, but not the level, of the TTK88 transcriptional repressor.

Alleles↗

Effectiveness of postmigration screening in controlling tuberculosis among refugees: a historical cohort study, 1984-1998.

OBJECTIVES: This study assessed the effectiveness of postmigration screening for the control of tuberculosis (TB) among refugee migrants. METHODS: We conducted a historical cohort study among 24 610 predominantly Southeast Asian refugees who had arrived in Sydney, Australia, between 1984 and 1994. All had been screened for TB before arrival and had radiologic follow-up for 18 months after arrival. Incident cases of TB were identified by record linkage analysis with confirmatory review of case notes. RESULTS: The crude annual incidence rate over 10-year follow-up was 74.9 per 100 000 person-years. Only 29.6% of the cases were diagnosed as a result of routine follow-up procedures. CONCLUSIONS: Enhanced passive case finding is likely to be more effective than active case finding for the control of TB among refugees.

Asia, Southeastern↗

[Clone and expression of human soluble CD14 and study of its function].

Human soluble CD14(sCD14) cDNA fragment was amplified using total RNA extracted from U937 cells by RT-PCR of sCD14 gene, and the recombinant expression plasmid pEF1/HisC/sCD14 348aa was constructed. Then the expression in eukaryotic cell was carry out by liposome transfection method. It demonstrated that the expression level was relatively high by scanning map identification. The expressed product was purified by immunoaffinity chromatography and the purity was above 90%. The changes of CD14 brought by LPS stimulating U937 cell proved the product had the function of combine with LPS.

Cloning, Molecular↗

[A simulation study of effects of depressed myocardial contractility on cardiovascular response to lower body negative pressure].

OBJECTIVE: To study the effects of depressed myocardial contractility induced by microgravity on cardiovascular response to orthostatic stress, and to investigate the role played by the changes of myocardial contractility in the mechanism of cardiovascular deconditioning and orthostatic intolerance induced by space weightlessness. METHOD: On the basis of our previous model used to simulate the cardiovascular response to lower body negative pressure (LBNP), the factor of changes of myocardial contractility was incorporated into the model by multiplying a coefficient to the maximum elastance of the heart working sub-model. By decreasing the coefficient progressively, then the changes of heart rate (HR), blood pressure (BP), and cardiac output (CO) during LBNP after 0 - 30% of myocardial contractility depression combined with 12% decrease of total blood volume were simulated. RESULT: Simulation results indicated that depressed myocardial contractility induces more augment of HR, and more decrease of BP and CO during LBNP. CONCLUSION: The depression of myocardial contractility degenerated cardiovascular response to orthostatic stress.

Blood Pressure↗

[Analysis of loss of heterozygosity on 19p in primary gastric cancer].

OBJECTIVE: To investigate the loss of heterozygosity (LOH) frequency of microsatellite loci in primary gastric cancer samples and locate the deleted regions on 19p in which might exist human gastric cancer related genes. METHODS: The LOH of microsatellite loci on chromosome 19p was analyzed using PCR-SSLP-silver stain method in 43 primary gastric cancers and their paired normal tissues. RESULTS: In 43 primary gastric tumors, LOH was detected on the site for D19S424(29.63%), D19S216(11.53%), D19S406 (33.33%), D19S413(8.57%), D19S221(13.15%), D19S226(8.00%), D19S411(6.45%), D19S883(6.89%), and D19S886(10.71%), microsatellite instability (MSI) was found at the same time at locus D19S886 (17.85%). CONCLUSION: The most common LOH occurrence at D19S406 and D19S424 might imply the existence of the potential genes related to the tumorigenesis of gastric cancer in these loci.

Chromosome Mapping↗

Retroviral vector containing human p16 gene and its inhibitory effect on Bcap-37 breast cancer cells.

OBJECTIVE: To study the effects of the p16 gene on tumor cell growth inhibition and cell cycle arrest. METHODS: The recombinant retroviral vector pLp16SN was constructed by cloning the human p16 cDNA into the retroviral vector pLXSN. Retroviruses with or without the p16 gene were obtained by transfecting pLp16SN and pLXSN vectors into PA317 cells. Bcap-37 human breast cancer cells were infected with these retroviruses followed by selection with G418. The expression of p16 was detected by Northern and Western blots. Cell biological characteristics, including cell growth rate, cell cycle and tumorigenesis in nude mice were assessed. RESULTS: Both mRNA and protein expression of p16 in Bcap-37 cells transfected with retroviral vector containing the p16 gene were much higher than that in Bcap-37 cells transfected with empty vector or parental Bcap-37 cells. Cell overexpressing the p16 gene exhibited a slower rate of growth, a higher percentage of cells in the G1 phase, and smaller tumors in nude mice, compared with parental Bcap-37 cells and cells transfected with empty vector. CONCLUSION: Overexpression of the p16 gene could suppress the growth of Bcap-37 breast cancer cells by arresting the cell cycle at the G1 to S-phase.

Breast Neoplasms↗

[Deletion mapping of chromosome 18q and Smad proteins expression analysis in urinary bladder carcinomas].

OBJECTIVE: To investigate the role of loss of heterozygosity (LOH) on chromosome 18q in the carcinogenesis and progression of urinary bladder cancer and to provide clues for early detection and positional cloning of related genes. METHODS: Deletion mapping was performed on 18q using 12 microsatellite markers. Immunohistochemistry staining was used to evaluate the expression level of two tumor suppressor candidates Smad 2 and Smad 4 in this region. RESULTS: LOH in at least one of the 12 microsatellites on 18q was detected in 84.2% (32/38) of patients with bladder cancer. The minimal deletion region included tumor suppressor candidate Smad 4. Immunohistochemical study revealed that 21.1% (8/38) of the cases had up-regulated Smad 2 protein and 34.2% (13/38) of the cases had down-regulated Smad 2 protein. Smad4 protein expression was down-regulated in 68.4% (26/38) of the cases but up-regulated Smad 4 expression was seen in only one case. CONCLUSIONS: LOH on 18q was closely linked with bladder cancer. The irregular expression of tumor suppressor candidates Smad 2 and Smad 4 may play important role in the initiation and progression of bladder neoplasms.

Adolescent↗

[A biomechanical model of left ventricle regional ischemia: a computer simulation].

Objective. To analyze the biomechanical mechanism of left ventricular regional ischemia and to investigate the changes of myocardial contractilities in different ventricular regions during regional ischemia. Method. A time-dependent mathematical model for simulating left ventricle regional ischemia has been developed basing on geometry of left ventricle, spatial angle distribution, propagation of electrical activation signals and biomechanical properties of cardiac muscle fibers. Then the model was incorporated into a multi-element circulatory model established by us previously. By using this model, some simulation experiments relating myocardium contractility to regional ischemia in inner or outer layers of ventricular wall were performed. Result. Myocardial contractility of the ischemic layers decreased whereas that of normal layers increased significantly. Compared with ischemia in outer layers of ventricular wall, ischemia in inner layers of ventricular wall had more effects upon cardiac function. Conclusion. The myocardium of normal region had the ability to increase its contractility in order to maintain a normal cardiac function. A method to simulate the relationship between cardiovascular function and left ventricular regional ischemia was developed.

Biomechanical Phenomena↗

Up-regulation of Phosphatidylinositol-3 Kinase Signaling in plcg1 Gene Null Fibroblasts.

Phospholipase C-gamma1(PLC-gamma1) and phosphatidylinositol-3 kinase(PI-3K) play crucial role in growth factor-induced cell growth and proliferation. To investigate the complementary mechanism of PLC-gamma1 in cell growth and epidermal growth factor (EGF)-induced mitogenic signaling, PLC-gamma1 deficient mouse embryonic fibroblasts(PLC-gamma1(-/-)) and its wild type(PLC-gamma1(+/+)) were exposed to U73122, a phospholipase C-specific inhibitor, or wortmannin, a PI-3K inhibitor then the clonogenicity, viability, EGF-induced DNA synthesis of the two cell lines were determined by cloning formation, MTT method and (3)H -thymidine incorporation assay. Results showed that either U73122 or wortmannin inhibited PLC-gamma1(-/-) and PLC-gamma1(+/+) cells in terms of EGF-induced DNA synthesis, cloning formation and cell viability, but PLC-gamma1(-/-) cells were more dependent on PI-3K and less dependent on PLC compared with wild types. The PLC-gamma1 signaling pathway of PLC-gamma1(-/-) cells might be complemented by PI-3K pathway, because after EGF stimulation, the tyrosine phospholation of p85alpha PI-3K increased significantly in PLC-gamma1(-/-), but not in PLC-gamma2(-/-), as Western blotting showed that there was neither complementary PLC-gamma2 expression in PLC-gamma1(-/-) cells, nor other PLC isozymes such as PLC-beta and PLC-delta. These results suggest the redundancy of EGF-mediated signaling and the complementary mechanism of PLC-gamma1 pathway.

Journal Article↗

Effects of depressed myocardial contractility induced by microgravity on cardiovascular response to orthostatic stress: a computer simulation.

The aim of present study is to investigate the role played by the depression of myocardial contractility in the mechanism of cardiovascular deconditioning and orthostatic intolerance (OI) induced by space weightlessness. Based on our previous model, which was used to simulate cardiovascular response to lower body negative pressure (LBNP), we incorporated the factor of changes of myocardial contractility into the model by multiplying a coefficient to the time-varying elastance that represents the changes of cardiac contractility. By decreasing the coefficient progressively, we simulated the changes of heart rate (HR), blood pressure (BP), and cardiac output (CO) during LBNP after 0-30% of myocardial contractility depression combined with 12% decrease of the total blood volume. Simulation results indicate that depressed myocardial contractility induces more augment of HR, and more decrement of BP and CO during LBNP and suggest that the depression of myocardial contractility degenerate cardiovascular response to orthostatic stress.

Blood Pressure↗

Regulation of invasive cell behavior by taiman, a Drosophila protein related to AIB1, a steroid receptor coactivator amplified in breast cancer.

Steroid hormones are key regulators of numerous physiological and developmental processes, including metastasis of breast and ovarian cancer. Here we report the identification of a Drosophila gene, named taiman, which encodes a steroid hormone receptor coactivator related to AIB1. Mutations in tai caused defects in the migration of specific follicle cells, the border cells, in the Drosophila ovary. Mutant cells exhibited abnormal accumulation of E-cadherin, beta-catenin, and focal adhesion kinase. TAI protein colocalized with the ecdysone receptor in vivo and augmented transcriptional activation by the ecdysone receptor in cultured cells. The finding of this type of coactivator required for cell motility suggests a novel role for steroid hormones, in stimulating invasive cell behavior, independent of effects on proliferation.

Animals↗

Predicting durability of a disease resistance gene based on an assessment of the fitness loss and epidemiological consequences of avirulence gene mutation.

Durability of plant disease resistance (R) genes may be predicted if the cost of pathogen adaptation to overcome resistance is understood. Adaptation of the bacterial blight pathogen, Xanthomonas oryzae pv. oryzae (Xoo), to virulence in rice is the result of the loss of pathogen avirulence gene function, but little is known about its effect on aggressiveness under field conditions. We evaluated the cost in pathogenic fitness (aggressiveness and persistence) associated with adaptation of Xoo to virulence on near-isogenic rice lines with single R genes (Xa7, Xa10, and Xa4) at two field sites endemic for bacterial blight. Disease severity was high in all 3 years on all lines except the line with Xa7. Of two Xoo lineages (groups of strains inferred to be clonally related based on DNA fingerprinting) detected, one, lineage C, dominated the pathogen population at both sites. All Xoo strains were virulent to Xa4, whereas only lineage C strains were virulent to Xa10. Only a few strains of lineage C were virulent to Xa7. Adaptation to virulence on Xa7 occurred through at least four different pathways and was associated with a reduction in aggressiveness. Loss of avirulence and reduced aggressiveness were associated with mutations at the 3' terminus of the avrXa7 allele. Strains most aggressive to Xa7 were not detected after the second year, suggesting they were less persistent than less aggressive strains. These experiments support the prediction that Xa7 would be a durable R gene because of a fitness penalty in Xoo associated with adaptation to Xa7.

Bacterial Proteins↗

Adenovirus-mediated overexpression of catalase in the cytosolic or mitochondrial compartment protects against cytochrome P450 2E1-dependent toxicity in HepG2 cells.

Cytochrome P450 2E1 (CYP2E1) is an effective producer of reactive oxygen species such as superoxide radical and hydrogen peroxide, which may contribute to the development of alcohol liver disease or cytotoxicity. To investigate the protective role of catalase against CYP2E1-dependent cytotoxicity, E47 cells, a transfected HepG2 cell line overexpressing CYP2E1, were infected with adenoviral vectors containing human catalase cDNA (AdCat) and catalase cDNA with a mitochondrial leader sequence (AdmCat). Forty-eight hours after infection with AdCat or AdmCat at a multiplicity of infection of 100, intracellular catalase protein was increased >2-fold compared with uninfected E47 cells and E47 cells infected with empty adenoviral vector (AdNull) as determined by Western blotting and catalase activity measurements. Overexpression of catalase in the cytosol (AdCat) and in mitochondria (AdmCat) was confirmed by confocal microscopy. Cell death caused by arachidonic acid plus iron was considerably suppressed in both AdCat- and AdmCat-infected E47 cells as determined by assays of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide absorbance, lactate dehydrogenase release, and morphology changes. AdCat- and AdmCat-infected cells were also more resistant to the loss of mitochondrial membrane potential and to the increase in lipid peroxidation induced by arachidonic acid and iron. This study indicates that catalase in the cytosol and catalase in mitochondria are capable of protecting HepG2 cells expressing CYP2E1 against cytotoxicity induced by oxidants that promote lipid peroxidation and suggests the possibility that such agents may be useful in protecting against the development of alcohol liver injury.

Adenoviridae↗

Geranylgeranylacetone enhances expression of thioredoxin and suppresses ethanol-induced cytotoxicity in cultured hepatocytes.

Geranylgeranylacetone (GGA) has been introduced into the clinical field as an anti-ulcer drug. In addition to protective effects on gastric mucosal cells, GGA also has anti-apoptotic effects against ischemia and reperfusion injury in hepatocytes and intestinal cells. However, the molecular mechanisms of the cytoprotective or anti-apoptotic effect of GGA are largely unknown. To explore the molecular mechanism of GGA action, we focused on thioredoxin (TRX), an endogenous-redox-acting molecule. We have demonstrated that GGA induces the messenger RNA and protein of TRX and affects the activation of transcription factors, AP-1 and NF-kappaB, and that GGA blunted ethanol-induced cytotoxicity of cultured hepatocytes. These results provide evidence suggesting that a possible novel molecular mechanism of GGA is to protect cells via the induction of TRX and the activation of transcription factors such as NF-kappaB and AP-1.

Animals↗

Membrane-embedded synaptotagmin penetrates cis or trans target membranes and clusters via a novel mechanism.

The synaptic vesicle protein synaptotagmin I has been proposed to serve as a Ca(2+) sensor for rapid exocytosis. Synaptotagmin spans the vesicle membrane once and possesses a cytoplasmic domain largely comprised of two C2 domains designated C2A and C2B. We have determined how deep the Ca(2+)-binding loops of Ca(2+).C2A penetrate into the lipid bilayer and report mutations in synaptotagmin that can uncouple membrane penetration from Ca(2+)-triggered interactions with the SNARE complex. To determine whether C2A penetrates into the vesicle ("cis") or plasma ("trans") membrane, we reconstituted a fragment of synaptotagmin that includes the membrane-spanning and C2A domain (C2A-TMR) into proteoliposomes. Kinetics experiments revealed that cis interactions are rapid (< or =500 micros). Binding in the trans mode was distinguished by the slow diffusion of trans target vesicles. Both modes of binding were observed, indicating that the linker between the membrane anchor and C2A domain functions as a flexible tether. C2A-TMR assembled into oligomers via a novel N-terminal oligomerization domain suggesting that synaptotagmin may form clusters on the surface of synaptic vesicles. This novel mode of clustering may allow for rapid Ca(2+)-triggered oligomerization of the protein via the membrane distal C2B domain.

Acrylamide↗

Approaches to functional genomics: potential of matrix-assisted laser desorption ionization--time of flight mass spectrometry combined with separation methods for the analysis of DNA in biological samples.

MALDI-TOF MS has potential as a valuable technique in DNA mapping studies and may well be complementary to other approaches to DNA analysis such as gel electrophoresis and sequencing. This study used 2,6-dihydroxyacetophenone (DHAP) mixed with diammonium hydrogen citrate (DAHC) as the matrix. In addition, recent technical advances such as time lag focussing (TLF) and better selection of matrices (such as 3-hydroxypicolinic acid (3 HPA) and picolinic acid (PA)) extended the range of DNA fragments that can be studied by this approach. The following samples were investigated: Poly-T mixture (dT 15, 19, 20, 25, 74 and 75), plasmid pBR322 derived oligonucleotides (10, 11, 12, 13, 14, 15, 19, 20 and 50 nucleotides long) and DNA fragments of 25, 36 and 37 base pairs corresponding to a fragment in the restriction map for the gene corresponding to the hexon protein of Adenovirus 2 and 5. The results were contrasted with similar analyses performed by ion-paired reversed-phase HPLC coupled to on-line electrospray mass spectrometry.

Chromatography, High Pressure Liquid↗