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Biomedical subjects

Tao Lu

Publications and source records attributed to Tao Lu.

At least 19 recordsLinked to original sources

Birnessite-mediated simultaneous remediation of lead and benzo[a]pyrene co-contaminated soils.

It is currently challenging to remediate soils co-contaminated by heavy metals and polycyclic aromatic hydrocarbons. Birnessite is a naturally ubiquitous manganese oxide mineral with strong oxidation and adsorption capacities, but its specific roles in pollutant transformation and interfacial interaction within co-contaminated systems remain elusive. This study investigated the simultaneous remediation of lead (Pb) and benzo[a]pyrene (BaP) in soils by birnessite through incubation experiments and density functional theory calculation. Birnessite treatment decreased CaCl2- and toxicity characteristic leaching procedure-extractable Pb content by 64.3% and 86.6% and reduced the BaP content by 33.8%. Mechanistically, Pb immobilization was primarily driven by spontaneous adsorption, including ion exchange and surface complexation, which facilitated Pb transformation into Fe-Mn oxide-bound fractions. Concurrently, BaP removal occurred via a synergistic pathway involving reactive species and electron transfer processes. Increasing dosage of birnessite promoted Pb immobilization, but had little effect on BaP oxidation. Moreover, the co-existing Pb affected birnessite-mediated BaP adsorption and oxidation by promoting the formation of [BaP-Pb]2+ and [BaP-Pb(H2O)]2+ complexes via cation-π interactions. These complexes were more preferentially adsorbed on birnessite compared with BaP molecules, but exhibited higher electron transfer barriers. The findings provide critical insights into the remediation of co-contaminated soils and the fate of co-existing contaminants.

Birnessite↗

Vitiligo prevalence study in Shaanxi Province, China.

BACKGROUND: Recent publications, especially those based on population surveys, show that the presumed vitiligo prevalence of 1-2% is overestimated. OBJECTIVE: To obtain the vitiligo prevalence in Shaanxi Province, China, through a population survey. METHODS: Approximately one-thousandth of the 36.05 million people in Shaanxi Province, China, were selected through stratified four-stage cluster sampling. They lived in 180 investigation units and all were investigated in a door-to-door survey. Vitiligo and suspected vitiligo patients were marked in the basic questionnaire. They were encouraged to complete a well-prepared questionnaire and send it back to the investigation center. The questionnaire assigned to the investigators contained questions about vitiligo characteristics, such as the area affected, number of areas, and whether or not the affected areas were covered by scurf. Professional dermatologists verified these results. RESULTS: There were 42,833 people in 180 investigation units. The sex, residence, and educational level of these individuals were representative of the population of Shaanxi Province. The investigation team reported 43 vitiligo patients and 14 with suspected vitiligo. During the verification period, three patients and all those with suspected vitiligo were excluded. In total, there were 40 patients (17 women and 23 men). Eleven lived in urban areas and 29 in rural areas. CONCLUSIONS: The prevalence of vitiligo in Shaanxi Province is 0.093% (95% confidence interval, 0.067-0.127%). No significant difference was found between males and females or between urban and rural residents.

Adolescent↗

Rad17 phosphorylation is required for claspin recruitment and Chk1 activation in response to replication stress.

The ATR-mediated checkpoint is not only critical for responding to genotoxic stress but also essential for cell proliferation. The RFC-related checkpoint protein Rad17, a phosphorylation substrate of ATR, is critical for ATR-mediated checkpoint signaling and cell survival. Here, we show that phosphorylation of Rad17 by ATR is important for genomic stability and restraint of S phase but is not essential for cell survival. The phosphomutant Rad17AA exhibits distinct defects in hydroxyurea- (HU) and ultraviolet- (UV) induced Chk1 activation, indicating that separate Rad17 functions are required differently in response to different types of replication interference. Although cells expressing Rad17AA can initiate Chk1 phosphorylation after HU treatment, they fail to sustain Chk1 phosphorylation after withdrawal of HU and are profoundly sensitive to HU. Importantly, we found that phosphorylated Rad17 interacts with Claspin and regulates its phosphorylation. These findings reveal a phosphorylation-dependent function of Rad17 in an ATR-Rad17-Claspin-Chk1-signaling cascade that responds to specific replication stress.

Adaptor Proteins, Signal Transducing↗

Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1.

Intracellular accumulation of mutant Huntingtin with expanded polyglutamine provides a context-dependent cytotoxicity critical for the pathogenesis of Huntington disease (Everett, C. M., and Wood, N. W. (2004) Brain 127, 2385-2405). Here we demonstrate that the accumulation of mutant Huntingtin is highly sensitive to the expression of beclin 1, a gene essential for autophagy. Moreover, we show that the accumulated mutant Huntingtin recruits Beclin 1 and impairs the Beclin 1-mediated long lived protein turnover. Thus, sequestration of Beclin 1 in the vulnerable neuronal population of Huntington disease patients might further reduce Beclin 1 function and autophagic degradation of mutant Huntingtin. Finally, we demonstrate that the expression of beclin 1 decreases in an age-dependent fashion in human brains. Because beclin 1 gene is haploid insufficient in regulating autophagosome function (Qu, X., Yu, J., Bhagat, G., Furuya, N., Hibshoosh, H., Troxel, A., Rosen, J., Eskelinen, E. L., Mizushima, N., Ohsumi, Y., Cattoretti, G., and Levine, B. (2003) J. Clin. Invest. 112, 1809-1820; Yue, Z., Jin, S., Yang, C., Levine, A. J., and Heintz, N. (2003) Proc. Natl. Acad. Sci. U. S. A. 100, 15077-15082), we propose that the age-dependent decrease of beclin 1 expression may lead to a reduction of autophagic activity during aging, which in turn promotes the accumulation of mutant Htt and the progression of the disease.

Adult↗

Comparison of 6-hydroxylmelatonin or melatonin in protecting neurons against ischemia/reperfusion-mediated injury.

The protective effect of exogenous melatonin or 6-hydroxylmelatonin on neurons was examined in N2a cells following exposure to oxygen-glucose-serum deprivation insults. After N2a cells cultured in vitro were deprived of glucose, serum and oxygen for 90 min, the different concentrations of melatonin or 6-hydroxylmelatonin were added to the medium. Then, treated cells were cultured for different intervals. At the end of the treatment, the collected culture solution was used for the analysis of the activity of lactate dehydrogenase (LDH) and the cells were used for the examination of the following parameters: cell viability (MTT), DNA fragmentation, reactive oxygen species (ROS) production, mitochondrial transmembrane potential, cytochrome C and caspase 3 activity. The results show that melatonin and 6-hydroxylmelatonin both reduced oxygen-glucose-serum deprivation-mediated N2a cell apoptosis, but they could not completely inhibit the apoptosis of the cells and the inhibitory effect of melatonin was stronger than that of 6-hydroxylmelatonin. Both of them could inhibit LDH and cytochrome C release and caspase 3 activity. Although 6-hydroxylmelatonin could no longer maintain mitochondrial transmembrane potential 6 h after reperfusion, its inhibitory effect on cytochrome C release from mitochondria and the scavenging role of ROS were stronger than those of melatonin. Moreover, melatonin promoted ROS production at the 15th min of the reperfusion, and then it began to remove ROS from cells. Our study showed that melatonin and 6-hydroxylmelatonin can be used as supplements in the treatment of neurological disorders involving oxidative stress. Melatonin serves as more than a ROS scavenger and its other roles await further study.

Animals↗

Operator expansions for polarization mode dispersion analysis and compensation.

We present analytic third- and fourth-order expansions of the Jones matrix as products of exponentials of individual matrices. In our first formalism, these are polarization mode dispersion (PMD) matrices of definite orders. We then discuss an alternative procedure that instead employs exponentials of general skew-Hermitian matrices with a low-order dependence on the deviation of the optical frequency from a central reference frequency. Our expressions correspond to PMD compensators formed from a succession of relatively simple optical components each of which has the frequency response of a single operator in the product.

Journal Article↗

Improved multicanonical algorithms.

We introduce several easily programmed techniques that enhance the accuracy of multicanonical sampling. With minor modifications to the standard technique, our methods achieve equivalent or enhanced accuracy compared with existing, often far more complex, algorithmic refinements. Despite their simple formulation, these procedures have been previously overlooked because of the low cost of additional realizations in numerical calculations. When applied in the context of our recently introduced experimental multicanonical measurements, however, significant time savings can result.

Journal Article↗

Determination of bioactive constituents in traditional Chinese medicines by CE with electrochemical detection.

This paper reviews the recent advances and the key strategies in capillary electrophoresis (CE) with electrochemical detection (ECD) for separating and detecting a variety of bioactive constituents in traditional Chinese medicines (TCMs). The subjects covered include the separation modes for the CE analysis of the constituents in TCMs, the CE-ECD system, the sample preparations of TCMs, the ECD of TCMs, the applications of CE-ECD in the determination of various bioactive constituents in Chinese medicinal materials and their preparations, the identification and differentiation of TCMs by CE-ECD, and future prospects. It is expected that CE-ECD will become a powerful tool in the herbal medicinal fields and will lead to the creation of truly routine devices for TCM analysis.

Drugs, Chinese Herbal↗

Oleandrin-mediated oxidative stress in human melanoma cells.

While certain cardiac glycoside compounds such as oleandrin, bufalin and digitoxin are known to be associated with potent cytotoxicity to human tumor cells, the mechanisms by which this effect is produced are not clear. We now demonstrate that incubation of human malignant melanoma BRO cells with oleandrin results in a time-dependent formation of reactive oxygen species (ROS). Use of Mito-SOX and dihydroethidine dyes revealed the presence of oleandrin-mediated superoxide anions. Formation of superoxide anions correlated with a loss in cellular viability, proliferation and cellular defense mechanisms such as GSH content. Oleandrin also resulted in an unusual time-dependent mitochondrial condensation in BRO cells that could be blocked with use of N-acetyl cysteine (NAC). NAC was also shown to block ROS formation and partially prevent oleandrin-mediated loss of cellular GSH. Taken as a whole, the data suggest that exposure of human tumor cells such as BRO to oleandrin results in the formation of superoxide anion radicals that mediate mitochondrial injury and loss of cellular GSH pools. These mechanisms play a role in cardiac glycoside mediated tumor cell injury. Conversely, incubation of NAC, a precursor to GSH, largely prevents oleandrin-mediated inhibition of proliferation and mitochondria structural changes.

Cardenolides↗

Mutagenesis by reversible promoter insertion to study the activation of NF-kappaB.

Genetic dissection of signaling pathways in mammalian cells involves screening or selecting phenotypic mutants obtained by a variety of techniques. Limitations in current methods include inadequate genome coverage and difficulty in validating the link between mutation and phenotype. We describe an improved method for insertional mutagenesis with retroviral vectors and show that the ability to induce mutations increases greatly if a randomly inserted promoter directs transcription into the host DNA. The mutant phenotype is due to the expression of a hybrid transcript derived from the vector and the insertion site. Because other alleles of the affected gene remain intact, the phenotype is dominant, but is reversible by inactivating the promoter, for example, by site-specific recombination. Importantly, in mutant clones with multiple inserts, limited excision yields progeny with different patterns of inserts remaining. Characterizing these progeny allows the mutant phenotype to be associated with a specific target gene. Relative simplicity and robust target validation make the method suitable for a broad range of applications. We have used this technique to search for proteins that regulate NF-kappaB-dependent signaling in human cells. Two validated targets are the relA gene, which codes for the NF-kappaB p65 subunit, and the NF-kappaB regulator act1. Overexpression of the corresponding proteins, caused by insertion of a promoter into the first intron of each gene, leads to NF-kappaB-dependent secretion of factors that activate NF-kappaB through cell-surface receptors, establishing an autocrine loop.

Adaptor Proteins, Signal Transducing↗

Instability of sonoluminescing bubbles under a nonspherical symmetrical acoustic-pressure perturbation.

The perturbation of nonspherical symmetrical acoustic pressure is added to the equation governing the spherical stability of sonoluminescing bubbles. The numerical calculations of the shape instability of sonoluminescing bubbles with the modified equation are conducted and the results are illustrated accordingly in the p(a) - R0 phase diagrams. The calculated results indicate that the stability region vanishes as the amplitude of the driving acoustic pressure p(a) arrives at the upper threshold ( approximately 1.6 atm) due to the perturbation of a small nonspherical symmetrical acoustic pressure (about a few Pa), which is in consistence with the experimental observations.

Journal Article↗

Lethality of quinolones against Mycobacterium smegmatis in the presence or absence of chloramphenicol.

Quinolones were examined for rapid lethal activity against Mycobacterium smegmatis in the presence and absence of chloramphenicol, an inhibitor of protein synthesis. C-8 methoxy, C-6 fluorine, and particular C-7 ring substituents enhanced rapid killing. With the surprising exception of moxifloxacin, higher quinolone concentrations were required for lethal activity in the presence of chloramphenicol than in its absence. Moxifloxacin was also unusual in lacking the time lag characteristic of fluoroquinolone lethality. Several fluoroquinolone dimers, which represent quinolones with large C-7 substituents, showed modest bacteriostatic activity. Unlike other quinolones, the dimers failed to display lethal activity. The insensitivity of moxifloxacin to chloramphenicol has not been observed with other bacteria and may therefore reflect unique aspects of mycobacterial gyrase.

Anti-Bacterial Agents↗

Chebyshev and Taylor approximations of polarization mode dispersion for improved compensation bandwidth.

We examine a series of experimentally realizable procedures for wide-bandwidth polarization mode dispersion compensation based on Taylor and Chebyshev approximations to the transfer matrix for light polarization in optical fibers. Our results demonstrate that a symmetric ordering of compensator elements in the Taylor procedure improves performance and that methods based on the Chebyshev approximation can significantly widen the compensation bandwidth.

Journal Article↗

Multicanonical comparison of polarization-mode dispersion compensator performance.

We employ a modified version of the multicanonical algorithm to evaluate the system penalties and outage probabilities of different polarization-mode dispersion compensators. The procedure determines the optimal operating conditions for each compensator architecture far more efficiently than the standard Monte Carlo algorithm.

Journal Article↗

Cytokine overexpression and constitutive NFkappaB in cancer.

The NFkappaB family of transcription factors, central mediators of immune responses, are also involved in oncogenesis. Loss of regulation of the normally latent NFkappaB contributes importantly to the deregulated growth, resistance to apoptosis and propensity to metastasize observed in many cancers. Thus, pathways for activation of NFkappaB are promising targets for new agents that may help to prevent or treat cancer. We find that the abnormal secretion of multiple cytokines that activate NFkappaB by binding to cell-surface receptors is one of the major causes of constitutive NFkappaB activity in cancer. A novel finding is that the latent form of TGFbeta, secreted by some of these cells, can activate NFkappaB. To understand the basis of this abnormal cytokine secretion, we are using forward genetic methods to identify specific causative mutations in cancer cells.

Animals↗

Disruption of the Rad9/Rad1/Hus1 (9-1-1) complex leads to checkpoint signaling and replication defects.

The checkpoint sliding-clamp complex, Rad9/Rad1/Hus1, plays a critical role during initiation of checkpoint signals in response to DNA damage and replication disruption. We investigated the impact of loss of Rad1 on checkpoint function and on DNA replication in mammalian cells. We show that RAD1 is an essential gene for sustained cell proliferation and that loss of Rad1 causes destabilization of Rad9 and Hus1 and consequently disintegration of the sliding-clamp complex. In Rad1-depleted cells, Atr-dependent Chk1 activation was impaired whereas Atm-mediated Chk2 activation was unaffected, suggesting that the sliding clamp is required primarily in Atr-dependent signal activation. Disruption of sliding-clamp function also caused a major defect in S-phase control. Rad1-depleted cells exhibited an RDS phenotype, indicating that damage-induced S-phase arrest was compromised by Rad1 loss. Furthermore, lack of Rad1 also affected the efficiency of replication recovery from DNA synthesis blockage, resulting in a prolonged S phase. These deficiencies may perpetually generate DNA strand breakage as we have found chromosomal abnormalities in Rad1-depleted cells. We conclude that the Rad9/Rad1/Hus1 complex is essential for Atr-dependent checkpoint signaling, which may play critical roles in the facilitation of DNA replication and in the maintenance of genomic integrity.

Cell Cycle↗

Gene regulation and DNA damage in the ageing human brain.

The ageing of the human brain is a cause of cognitive decline in the elderly and the major risk factor for Alzheimer's disease. The time in life when brain ageing begins is undefined. Here we show that transcriptional profiling of the human frontal cortex from individuals ranging from 26 to 106 years of age defines a set of genes with reduced expression after age 40. These genes play central roles in synaptic plasticity, vesicular transport and mitochondrial function. This is followed by induction of stress response, antioxidant and DNA repair genes. DNA damage is markedly increased in the promoters of genes with reduced expression in the aged cortex. Moreover, these gene promoters are selectively damaged by oxidative stress in cultured human neurons, and show reduced base-excision DNA repair. Thus, DNA damage may reduce the expression of selectively vulnerable genes involved in learning, memory and neuronal survival, initiating a programme of brain ageing that starts early in adult life.

Adult↗