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Biomedical subjects

Ping Xie

Publications and source records attributed to Ping Xie.

At least 19 recordsLinked to original sources

Limping of homodimeric kinesin motors.

Conventional kinesin, a homodimeric motor protein that transports cargo in various cells, walks limpingly along microtubule. Here, based on our previously proposed partially coordinated hand-over-hand model, we present a new mechanism for the limping behaviors of both wild-type and mutant kinesin homodimers. The limping is caused by different vertical forces acting on the heads in two successive steps during the processive movement of the dimer. From the model, various theoretical results, such as the dependences of the mean dwell time and dwell time ratio on the coiled-coil length and on the external load as well as the effect of vertical force on velocity, are in good agreement with previous experimental results. We predict that a high degree of limping will correlate strongly with a high sensitivity of ATP turnover rate to upwards force.

Animals↗

Model for forward polymerization and switching transition between polymerase and exonuclease sites by DNA polymerase molecular motors.

Based on the available crystal structure a model is presented for the polymerization activity and switching transition between polymerase and exonuclease sites of a DNA polymerase molecular motor. Using the model, the fast polymerization rate for correctly base-paired DNA and much reduced polymerization rate after an incorporation of a mismatched base can be well explained. The dependences of the polymerization rate and exonuclease rate on mechanical tension acting on the DNA template are studied. The switching rates between the two sites are analyzed. All the results show good quantitative agreement with the available experimental results.

Base Pairing↗

In situ studies on the distribution patterns and dynamics of microcystins in a biomanipulation fish--bighead carp (Aristichthys nobilis).

The distribution and dynamics of microcystins in various organs of the phytoplanktivorous bighead carp were studied monthly in Lake Taihu, which is dominated by toxic cyanobacteria. There was a good agreement between LC-MS and HPLC-UV determinations. Average recoveries of spiked fish samples were 63% for MC-RR and 71% for MC-LR. The highest MC contents in intestine, liver, kidney and spleen were 85.67, 2.83, 1.70 and 1.57 microg g-1 DW, respectively. MCs were much higher in mid-gut walls (1.22 microg g-1 DW) than in hind- and fore-gut walls (0.31 and 0.18 microg g-1 DW, respectively), suggesting the importance of mid-gut wall as major site for MC absorption. A cysteine conjugate of MC-LR was detected frequently in kidney. Among the muscle samples analyzed, 25% were above the provisional tolerable daily intake level by WHO. Bighead is strongly resistant to microcystins and can be used as biomanipulation fish to counteract cyanotoxin contamination in eutrophic waters.

Animals↗

Model for helicase translocating along single-stranded DNA and unwinding double-stranded DNA.

A model is proposed for non-hexameric helicases translocating along single-stranded (ss) DNA and unwinding double-stranded (ds) DNA. The translocation of a monomeric helicase along ssDNA in weakly-ssDNA-bound state is driven by the Stokes force that is resulted from the conformational change following the transition of the nucleotide state. The unwinding of dsDNA is resulted mainly from the bending of ssDNA induced by the strong binding force of helicase with dsDNA. The interaction force between ssDNA and helicases in weakly-ssDNA-bound state determines whether monomeric helicases such as PcrA can unwind dsDNA or dimeric helicases such as Rep are required to unwind dsDNA.

DNA↗

The acute effects of microcystin LR on the transcription of nine glutathione S-transferase genes in common carp Cyprinus carpio L.

The glutathione S-transferases play important roles in the detoxification of microcystin. In this experiment, nine glutathione S-transferase genes including cytosolic GSTs (rho, mu, theta, alpha and pi), mitochondrial GST (kappa) and microsomal GSTs (mGST1, mGST2 and mGST3) were cloned from common carp Cyprinus carpio. The mRNA abundance of each carp GST isoform in liver was analyzed by real time PCR. The relative changes after stimulation with microcystin LR were also analyzed: increased levels of transcription of GST alpha, rho and mGST3 isoforms were detected at 6h post stimulation; the transcription of mu, theta and mGST2 isoforms were relatively stable; and all the GST isoforms except GST kappa and rho recovered to original levels compared with controls at 72 h. It is suggested that MC-LR showed different effects on the transcription of nine carp GST isoforms.

Animals↗

Effects of nonylphenol on the growth and microcystin production of Microcystis strains.

Both organic pollution and eutrophication are prominent environmental issues concerning water pollution in the world. It is important to reveal the effects of organic pollutants on algal growth and toxin production for assessing ecological risk of organic pollution. Since nonylphenol (NP) is a kind of persistent organic pollutant with endocrine disruptive effect which exists ubiquitously in environments, NP was selected as test compound in our study to study the relationship between NP stress and Microcystis growth and microcystin production. Our study showed that responses of toxic and nontoxic Microcystis aeruginosa to NP stress were obviously different. The growth inhibition test with NP on M. aeruginosa yielded effect concentrations E(b)C(50) values within this range of 0.67-2.96 mg/L. The nontoxic M.aeruginosa strains were more resistant to NP than toxic strains at concentration above 1mg/L. Cell growth was enhanced by 0.02-0.2 mg/L NP for both toxic and nontoxic strains, suggesting a hormesis effect of NP on M. aeruginosa. Both toxic and nontoxic strains tended to be smaller with increasing NP. But with the increased duration of the experiment, both the cell size and the growth rate began to resume, suggesting a quick adaptation of M. aeruginosa to adverse stress. NP of 0.05-0.5 mg/L significantly promoted microcystin production of toxic strain PCC7820, suggesting that NP might affect microcystin production of some toxic M. aeruginosa in the field. Our study showed that microcystin excretion was species specific that up to 75% of microcystins in PCC7820 were released into solution, whereas >99% of microcystins in 562 remained in algal cells after 12 days' incubation. NP also significantly influenced microcystin release into cultural media. The fact that NP enhanced growth and toxin production of M. aeruginosa at low concentrations of 0.02-0.5 mg/L that might be possibly found in natural freshwaters implies that low concentration of NP may favor survival of M. aeruginosa in the field and may play a subtle role in affecting cyanobacterial blooms and microcystin production in natural waters.

Bacterial Proteins↗

A model for biased diffusion of collagenase along collagen fibrils.

We present a model to describe the biased diffusion of a collagenase along collagen fibrils. Based on the structures of collagen fibril and collagenase, the interaction is described by a one-dimensional potential that is symmetric in the region of no cleavage and asymmetric in the cleavage region. We show that the mean velocity of the unidirectional diffusion of the collagenase depends on the three parameters: the asymmetric ratio of the local potential in the cleavage region, the chemical reaction rate of proteolysis and the jumping rate of collagenase between two neighboring tracks. We calculate the correlation function and the mean transport velocity for both wild-type and mutant collagenases along collagen fibrils, the results of which are consistent with the previous experiments.

Animals↗

Brownian dynamics simulation of directional sliding of histone octamers caused by DNA bending.

Chromatin-remodeling complexes such as SWI/SNF and RSC of yeast can perturb the structure of nucleosomes in an ATP-dependent manner. Experimental results prove that this chromatin remodeling process involves DNA bending. We simulate the effect of DNA bending, caused by chromatin-remodeling complexes, on directional sliding of histone octamers by Brownian dynamics simulation. The simulation results show that, after a DNA loop being generated at the side of a nucleosome, the histone octamer slides towards this DNA loop until the loop disappears. The DNA loop size is an important factor affecting the process of directional sliding of the histone octamer.

Anisotropy↗

Cooperation between TNF receptor-associated factors 1 and 2 in CD40 signaling.

TNFR-associated factor 1 (TRAF1) is unique among the TRAF family, lacking most zinc-binding features, and showing marked up-regulation following activation signals. However, the biological roles that TRAF1 plays in immune cell signaling have been elusive, with many reports assigning contradictory roles to TRAF1. The overlapping binding site for TRAFs 1, 2, and 3 on many TNFR superfamily molecules, together with the early lethality of mice deficient in TRAFs 2 and 3, has complicated the quest for a clear understanding of the functions of TRAF1. Using a new method for gene targeting by homologous recombination in somatic cells, we produced and studied signaling by CD40 and its viral oncogenic mimic, latent membrane protein 1 (LMP1) in mouse B cell lines lacking TRAF1, TRAF2, or both TRAFs. Results indicate that TRAFs 1 and 2 cooperate in CD40-mediated activation of the B cell lines, with a dual deficiency leading to a markedly greater loss of function than that of either TRAF alone. In the absence of TRAF1, an increased amount of TRAF2 was recruited to lipid rafts, and subsequently, more robust degradation of TRAF2 and TRAF3 was induced in response to CD40 signaling. In contrast, LMP1 did not require either TRAFs 1 or 2 to induce activation. Taken together, our findings indicate that TRAF1 and TRAF2 cooperate in CD40 but not LMP1 signaling and suggest that cellular levels of TRAF1 may play an important role in modulating the degradation of TRAF2 and TRAF3 in response to signals from the TNFR superfamily.

Animals↗

Mechanochemical couplings of kinesin motors.

Kinesins are molecular motors capable of moving processively along microtubule in a stepwise manner by hydrolyzing ATP. Numerous experimental results on various aspects of their dynamical behaviours are available in literature. Although a number of models of tightly coordinated mechanism have been proposed to explain some experimental results, up to now no good explanation has been given to all these experimental results by using a single model. We have recently proposed such a model of partially coordinated hand-over-hand moving mechanism. In this paper, we use this model to study in detail various aspects of the dynamical properties of single kinesin molecules. We show that kinesin dimers walk hand-over-hand along microtubules in a partially coordinated rather than a tightly coordinated manner. The degree of coordination depends on the ratio of the two heads' ATPase rates that are in turn determined by both internal elastic force and external load. We have tested this model using various available experimental results on different samples and obtained a good agreement between the theory and the experiments.

Adenosine Diphosphate↗

Supramolecular template-directed synthesis of perfect phenelenediimino-bridged ladderlike polyphenylsiloxanes.

A template synthesis of the soluble, high molecular weight (Mw), and perfect p-phenylenediimino (p-PDA)-bridged ladderlike polyphenylsiloxane (PLPS) is reported. First, N,N'-bis(phenyldichlorosilyl)-p-PDA monomers were self-assembled into a perfect ladder superstructure (LS) by concerted interaction of aromatic pi-pi stacking and hydrogen bonding. Then the LS underwent a novel stoichiometric hydrolysis/dehydrochlorination-condensation reaction instead of the usual hydrolysis/dehydration-condensation reaction, leading to the PLPS. The perfect ladder structures of both the PLPS and, in particular, the unstable supramolecular LS were confirmed as follows. 1) There are two Bragg peaks in solid and/or solution X-ray diffraction (XRD) spectra representing the ladder width (w) and ladder thickness (t); these peaks were consistent with those calculated by molecular simulation. 2) Both the PLPS and LS have extremely sharp absorption peaks with small half-peak widths (Delta(1/2) < 0.3 ppm) in 29Si NMR spectra, suggesting the presence of the perfect ladder structure for PLPS and LS. 3) Moreover, no noticeable absorption peaks for the Si-OH and NH2 groups were observed in FT-IR and 29Si NMR spectra, indicating that the Si-N bond of the [triple bond]Si-NH-C6H4-NH-Si[triple bond] ladder rung of PLPS and LS is not cleaved. 4) Both PLPS and LS show similar emission peaks (in fluorescence spectroscopy) attributed to the excimer formed by face-to face pi-pi stacking of phenyl groups along the ladder chain rather than a branched direction. 5) Differential scanning calorimetry (DSC) measurements indicate a high glass temperature (Tg = 176.4 degrees C) for PLPS. As circumstantial evidence, this result further indicates very high stiffness of PLPSs ladder backbone as compared with flexible single-chain polyphenylmethylsiloxane with a low Tg = -69.4 degrees C.

Journal Article↗

Land-cover changes in an urban lake watershed in a mega-city, Central China.

Urbanization can exert a profound influence on land covers and landscape characteristics. In this study, we characterize the impact of urbanization on land cover and lacustrine landscape and their consequences in a large urban lake watershed, Donghu Lake watershed (the largest urban lake in China), Central China, by using Landsat TM satellite images of three periods of 1987, 1993 and 1999 and ground-based information. We grouped the land covers into six categories: water body, vegetable land, forested land, shrub-grass land, open area and urban land, and calculated patch-related landscape indices to analyze the effects of urbanization on landscape features. We overlaid the land cover maps of the three periods to track the land cover change processes. The results indicated that urban land continuously expanded from 9.1% of the total watershed area in 1987, to 19.4% in 1993, and to 29.6% in 1999. The vegetable land increased from 7.0% in 1987, 11.9% in 1993, to 13.9% in 1999 to sustain the demands of vegetable for increased urban population. Concurrently, continuous reduction of other land cover types occurred between 1987 and 1999: water body decreased from 30.4% to 23.8%, and forested land from 33.6% to 24.3%. We found that the expansion of urban land has at least in part caused a decrease in relatively wild habitats, such as urban forest and lake water area. These alterations had resulted in significant negative environmental consequences, including decline of lakes, deterioration of water and air quality, and loss of biodiversity.

Agriculture↗

A hand-over-hand diffusing model for myosin-VI molecular motors.

Single molecules of dimeric myosin-VI have been demonstrated to be able to move processively towards the pointed end of actin filament with a mean step size of approximately 36 nm. Here we present a hand-over-hand diffusing mechanism for this unidirectional movement. Based on this mechanism, its dynamical behaviors such as the step-size distribution, dwell-time distributions and mean dwell time at various ATP and ADP concentrations and under various loads are studied in detail. The calculated results show good agreement with previous experimental results. The processive movement of mutant myosin-V with its neck domains truncated to only one IQ motif can also be explained by using this hand-over-hand diffusing model.

Actins↗

Escherichia coli RecQ is a rapid, efficient, and monomeric helicase.

RecQ family helicases play a key role in chromosome maintenance. Despite extensive biochemical, biophysical, and structural studies, the mechanism by which helicase unwinds double-stranded DNA remains to be elucidated. Using a wide array of biochemical and biophysical approaches, we have previously shown that the Escherichia coli RecQ helicase functions as a monomer. In this study, we have further characterized the kinetic mechanism of the RecQ-catalyzed unwinding of duplex DNA using the fluorometric stopped-flow method based on fluorescence resonance energy transfer. Our results show that RecQ helicase binds preferentially to 3'-flanking duplex DNA. Under the pre-steady-state conditions, the burst amplitude reveals a 1:1 ratio between RecQ and DNA substrate, suggesting that an active monomeric form of RecQ helicase is involved in the catalysis. Under the single-turnover conditions, the RecQ-catalyzed unwinding is independent of the 3'-tail length, indicating that functional interactions between RecQ molecules are not implicated in the DNA unwinding. It was further determined that RecQ unwinds DNA rapidly with a step size of 4 bp and a rate of approximately 21 steps/s. These kinetic results not only further support our previous conclusion that E. coli RecQ functions as a monomer but also suggest that some of the Superfamily 2 helicases may function through an "inchworm" mechanism.

Adenosine Triphosphatases↗

Development of tolerance against toxic Microcystis aeruginosa in three cladocerans and the ecological implications.

This is the first experimental study to compare difference in the development of tolerance against toxic Microcystis among multi-species of cladocerans (Daphnia, Moina and Ceriodaphnia) pre-exposed to two M. aeruginosa PCC7820 strains (MC-containing and MC-free). Zooplankton were divided into S population (fed Scenedesmus), M-F population (fed Scenedesmus+MC-free Microcystis), and M-C population (fed Scenedesmus+MC-containing Microcystis). M-F and M-C populations were pre-exposed to Microcystis strains for 4 weeks, and their newborns were collected for experiments. A pre-exposure to MC-containing or MC-free Microcystis increased tolerance against toxic Microcystis. The marked increases in survival rate and median lethal time (LT(50), 100-194% increase) in the M-C population of Ceriodaphnia suggest that small-sized cladocerans may develop stronger tolerance against Microcystis than large-sized ones when both groups are exposed to toxic Microcystis. This may explain why dominant Daphnia is usually replaced by small-sized cladocerans when cyanobacteria bloomed in summer in eutrophic lakes.

Animals↗

Model for unidirectional movement of axonemal and cytoplasmic dynein molecules.

A model for the unidirectional movement of dynein is presented based on the structural observations and biochemical experimental results available. In this model, the binding affinity of dynein for microtubule (MT) is independent of its nucleotide state and the change between strong and weak MT-binding is determined naturally by the variation of relative orientation between the stalk and MT, as the stalk rotates following nucleotide-state transition. Thus the enigmatic communication from the adenosine triphosphate (ATP)-binding site in the globular domain to the far MT-binding site in the tip of the stalk, which is a prerequisite in conventional models, is not required. Using the present model, the previous experimental results such as the effect of ATP and adenosine diphosphate (ADP) bindings on dissociation of dynein from MT, the movement of single-headed axonemal dyneins at saturating ATP concentration, the load dependence of step-size for the movement of two-headed cytoplasmic dyneins and the dependence of stall force on ATP concentration can be well explained.

Animals↗

Expression and functional characteristics of tubular transporters: P-glycoprotein, PEPT1, and PEPT2 in renal mass reduction and diabetes.

Renal mass reduction is associated with a compromise in renal excretion, and thus dosages of drugs need to be adjusted to avoid adverse reactions and to ensure their effectiveness. A prototypic example is patients who had undergone transplantation due to a variety of causes, including diabetic nephropathy; the latter appears to be the major cause of renal failure requiring hemodialysis and transplantation. Conceivably, hyperglycemia with reduced renal mass interferes in the delivery of xenobiotics handled by various tubular transporters. In this investigation, effect of renal mass reduction/hyperglycemia on gene and protein expression of P-glycoprotein (Pgp), PEPT1, and PEPT2 was assessed. Also, [H(3)]glycylsarcosine uptake, a prototype of dipeptide, was measured in various groups of rats: sham-operated, uninephrectomized, streptozotocin-induced diabetes, and diabetic + uninephrectomized. An increase in Pgp, PEPT1, and PEPT2 expression was observed in kidneys of uninephrectomy rats, the highest being in the Pgp. Similarly, an increase was observed in diabetic rats who had undergone uninephrectomy, although less than those with nephrectomy alone. No differences were observed between sham-operated and diabetic groups. Increased uptake of [H(3)]glycylsarcosine was also seen in uninephrectomised rats. A modest uptake was observed in diabetic rats who had undergone uninephrectomy. The data suggest that uninephrectomy induces an increase in the expression and activity of transporters localized to renal tubular epithelial brush border. The fact that upregulation and activity of the peptide transporters were less in kidneys of diabetic animals who had undergone uninephrectomy compared with uninephrectomy alone suggests that hyperglycemia interferes in their expression and activity during the compensatory phase.

ATP Binding Cassette Transporter, Subfamily B, Mem↗