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Biomedical subjects

Miao Wang

Publications and source records attributed to Miao Wang.

At least 19 recordsLinked to original sources

Genomic and evolutionary basis of parthenogenesis in a disease-vector tick species.

Haemaphysalis longicornis is an important tick species and pathogen vector characterized by the co-circulation of triploid parthenogenetic and diploid bisexual strains. However, the evolutionary basis of parthenogenesis in this species is unclear. Here we report reference-quality, haplotype-resolved genome assemblies of the parthenogenetic strain and two reference-quality genomes of the bisexual strains. Comparative genomic analysis revealed high collinearity between the parthenogenetic and bisexual genomes, with a stable chromosomal architecture maintained among the three haplotypes of the parthenogenetic strain. The parthenogenetic H. longicornis genome exhibited a major expansion in cell cycle-related gene families, including the inhibitor of apoptosis protein (IAP) family, but was characterized by a contraction in other gene families. Population resequencing of 179 individuals revealed two distinct subpopulations, with chromosome 7 harbouring high genetic differentiation and several candidate genes probably associated with parthenogenesis. Functional experiments showed that knockdown of the BIRC5 gene, a member of the IAP family, suppressed oviposition in both strains, with the parthenogenetic strain exhibiting milder adverse effects probably due to a stronger transcriptional response. Overall, our results reveal the genomic and evolutionary features associated with polyploid parthenogenesis in H. longicornis.

Animals↗

APS-mediated ubiquitination of the insulin receptor enhances its internalization, but does not induce its degradation.

APS, a tyrosine kinase adaptor protein with pleckstrin homology and Src homology 2 domains, is rapidly and strongly tyrosine-phosphorylated by insulin receptor kinase upon insulin stimulation. We have previously shown that APS knockout mice have increased insulin sensitivity, and that this enhancement is possibly due to increased insulin-response on adipose tissues. However, the function of APS in insulin signaling has so far been controversial. Here, we report that APS enhanced ligand-dependent multi-ubiquitination of the insulin receptor (IR) in CHO cells overexpressing the IR. APS-mediated ubiquitination of the IR induced enhancement of the IR internalization, but did not affect the IR degradation. This finding shows one of the pleiotropic functions of APS in insulin signaling.

Adaptor Proteins, Signal Transducing↗

Deletion of microsomal prostaglandin E synthase-1 augments prostacyclin and retards atherogenesis.

Prostaglandin (PG) E(2) is formed from PGH(2) by a series of PGE synthase (PGES) enzymes. Microsomal PGES-1(-/-) (mPGES-1(-/-)) mice were crossed into low-density lipoprotein receptor knockout (LDLR(-/-)) mice to generate mPGES-1(-/-) LDLR(-/-)s. Urinary 11alpha-hydroxy-9, 15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M) was depressed by mPGES-1 deletion. Vascular mPGES-1 was augmented during atherogenesis in LDLR(-/-)s. Deletion of mPGES-1 reduced plaque burden in fat-fed LDLR(-/-)s but did not alter blood pressure. mPGES-1(-/-) LDLR(-/-) plaques were enriched with fibrillar collagens relative to LDLR(-/-), which also contained small and intermediate-sized collagens. Macrophage foam cells were depleted in mPGES-1(-/-) LDLR(-/-) lesions, whereas the total areas rich in vascular smooth muscle cell (VSMC) and matrix were unaltered. mPGES-1 deletion augmented expression of both prostacyclin (PGI(2)) and thromboxane (Tx) synthases in endothelial cells, and VSMCs expressing PGI synthase were enriched in mPGES-1(-/-) LDLR(-/-) lesions. Stimulation of mPGES-1(-/-) VSMC and macrophages with bacterial LPS increased PGI(2) and thromboxane A(2) to varied extents. Urinary PGE-M was depressed, whereas urinary 2,3-dinor 6-keto PGF(1alpha), but not 2,3-dinor-TxB(2), was increased in mPGES-1(-/-) LDLR(-/-)s. mPGES-1-derived PGE(2) accelerates atherogenesis in LDLR(-/-) mice. Disruption of this enzyme retards atherogenesis, without an attendant impact on blood pressure. This may reflect, in part, rediversion of accumulated PGH(2) to augment formation of PGI(2). Inhibitors of mPGES-1 may be less likely than those selective for cyclooxygenase 2 to result in cardiovascular complications because of a divergent impact on the biosynthesis of PGI(2).

Animals↗

Miniature toroidal radio frequency ion trap mass analyzer.

A miniature ion trap mass analyzer is reported. The described analyzer is a 1/5-scale version of a previously reported toroidal radio frequency (rf) ion trap mass analyzer. The toroidal ion trap operates with maximum rf trapping voltages about 1 kVp-p or less; however despite the reduced dimensions, it retains roughly the same ion trapping capacity as conventional 3D quadrupole ion traps. The curved geometry provides for a compact mass analyzer. Unit-mass resolved mass spectra for n-butylbenzene, xenon, and naphthalene are reported and preliminary sensitivity data are shown for naphthalene. The expected linear mass scale with rf amplitude scan is obtained when scanned using a conventional mass-selective instability scan mode combined with resonance ejection.

Journal Article↗

Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular function.

We investigated the mechanisms by which inhibitors of prostaglandin G/H synthase-2 (PGHS-2; known colloquially as COX-2) increase the incidence of myocardial infarction and stroke. These inhibitors are believed to exert both their beneficial and their adverse effects by suppression of PGHS-2-derived prostacyclin (PGI(2)) and PGE(2). Therefore, the challenge remains to identify a mechanism whereby PGI(2) and PGE(2) expression can be suppressed while avoiding adverse cardiovascular events. Here, selective inhibition, knockout, or mutation of PGHS-2, or deletion of the receptor for PGHS-2-derived PGI(2), was shown to accelerate thrombogenesis and elevate blood pressure in mice. These responses were attenuated by COX-1 knock down, which mimics the beneficial effects of low-dose aspirin. PGE(2) biosynthesis is catalyzed by the coordinate actions of COX enzymes and microsomal PGE synthase-1 (mPGES-1). We show that deletion of mPGES-1 depressed PGE(2) expression, augmented PGI(2) expression, and had no effect on thromboxane biosynthesis in vivo. Most importantly, mPGES-1 deletion affected neither thrombogenesis nor blood pressure. These results suggest that inhibitors of mPGES-1 may retain their antiinflammatory efficacy by depressing PGE(2), while avoiding the adverse cardiovascular consequences associated with PGHS-2-mediated PGI(2) suppression.

Animals↗

Chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats.

AIM: To study chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats. METHODS: In anesthetized rats, the carotid blood pressure, left ventricular pressure of the heart and the urinary bladder pressure were recorded. RESULTS: Administration of S-doxazosin at 0.25, 2.5, 25, and 250 nmol/kg iv produced a dose-dependent decrease in blood pressure, but its depressor effect was significantly weaker than that induced by R-doxazosin and racemic-doxazosin (rac-doxazosin), and the ED(30) values (producing a 30% decrease in mean arterial pressure) of R-doxazosin, rac-doxazosin and S-doxazosin were 15.64, 45.93, and 128.81, respectively. Rac-doxazosin and its enantiomers administered cumulatively in anesthetized rats induced a dose-dependent decrease in the left ventricular systolic pressure and +/-dp/dt(max), and the potency order of the 3 agents was R-doxazosin > rac-doxazosin > S-doxazosin. Rac-doxazosin and its enantiomers decreased the vesical micturition pressure dose-dependently at 2.5, 25, and 250 nmol/kg, and the inhibitory potency among the 3 agents was not significantly different. CONCLUSION: S-doxazosin decreases the carotid blood pressure and left ventricular pressure of the heart less than R-doxazosin and rac-doxazosin, but its effect on the vesical micturition pressure is similar to R-doxazosin and rac-doxazosin, indicating that S-doxazosin has chiral selectivity between cardiovascular system and urinary system in anesthetized rats.

Adrenergic alpha-Antagonists↗

Characterization of an extracellular protease and its cDNA from the nematode-trapping fungus Monacrosporium microscaphoides.

To better exploit the biocontrol potential of nematophagous fungi, it is important to fully understand the molecular background of the infection process. In this paper, several nematode-trapping fungi were surveyed for nematocidal activity. From the culture filtrate of Monacrosporium microscaphoides, a neutral serine protease (designated Mlx) was purified by chromatography. This protease could immobilize the nematode Penagrellus redivivus in vitro and degrade its purified cuticle, suggesting that Mlx could serve as a virulence factor during infection. Characterization of the purified protease revealed a molecular mass of approximately 39 kDa, an isoelectric point of 6.8, and optimum activity at pH 9 at 65 degrees C. Mlx has broad substrate specificity, and it hydrolyzes protein substrates, including casein, skimmed milk, collagen, and bovine serum albumin. The gene encoding Mlx was also cloned and the nucleotide sequence was determined. The deduced amino acid sequence contained the conserved catalytic triad of aspartic acid--histidine--serine and showed high similarity with two cuticle-degrading proteases (PII and Aoz1), which were purified from the nematode-trapping fungus Arthrobotrys oligospora. Research on infection mechanisms of nematode-trapping fungi has thus far only focused on A. oligospora. However, little is known about other nematode-trapping fungi. Our report is among the first to describe the purification and cloning of an infectious protease from a different nematode-trapping fungus.

Animals↗

[Effects of Qinggan Huoxue Recipe and its decomposed formulas on CD14, Toll like receptor 4 and nuclear factor-kappaB expressed by Kupffer cells].

OBJECTIVE: To investigate the effects of Qinggan Huoxue Recipe (QGHXR), a compound Chinese herbal medicine, and its decomposed formulas Qinggan Recipe (QGR) and Huoxue Recipe (HXR) on expressions of CD14, Toll like receptor 4 (TLR(4)) and nuclear factor-kappaB (NF-kappaB) in Kupffer cells. METHODS: The isolated primary rat Kupffer cells were treated with lipopolysaccharide (LPS) for a certain period of time, a series of concentrations of drug-containing serums of QGHXR and its decomposed formulas were added, the expressions of NF-kappaB, tumor necrosis factor-alpha (TNF-alpha), CD14, and TLR(4) of the Kupffer cells were detected in different culture conditions by using Western blot, real-time reverse transcription polymerase chain reaction (RT-PCR) and ELISA methods respectively. RESULTS: QGR could down-regulate the expression of membrane receptor CD14, but the expression of NF-kappaB and TNF-alpha were not significantly decreased after QGR treatment. HXR could down-regulate the expression of membrane receptor TLR4 and inhibit the expressions of NF-kappaB and TNF-alpha. QGHXR could down regulate the expressions of membrane receptors CD14 and TLR(4) and inhibit the expressions of NF-kappaB and TNF-alpha. CONCLUSION: QGHXR can protect liver cells by down regulating the expressions of CD14, TLR(4) and NF-kappaB and inhibiting TNF-alpha expression.

Animals↗

[Respiration rate of broadleaved Korean pine forest ecosystem in Changbai Mountains].

In this paper, the respiration rates of soil, foliage, and stem and branch in the broadleaved Korean pine forest ecosystem of Changbai Mountains were measured by Li-6400 CO2 analysis system in 2003, with the microclimate factors determined synchronously. The correlation models of ecosystem respiration with environmental factors were established, and the respiration rate of each component of the ecosystem was estimated based on the vegetation characteristics of the broadleaved Korean pine forest. The results showed that the annual total respiration rate of the ecosystem was 1602. 8 g C x m(-2), with a mean of (4. 37+/-2. 98) micromol x m(-2) x s(-1) , and the respiration of soil, foliage, and stem and branch contributed about 63% , 21% , and 16% of the total, respectively. There was a significant correlation between system respiration and daily mean air and soil temperature, and about 87% and 95% of the ecosystem respiration could be explained by the air and soil temperature, respectively.

China↗

Cyclooxygenases, thromboxane, and atherosclerosis: plaque destabilization by cyclooxygenase-2 inhibition combined with thromboxane receptor antagonism.

BACKGROUND: Antagonism or deletion of the receptor (the TP) for the cyclooxygenase (COX) product thromboxane (Tx)A2, retards atherogenesis in apolipoprotein E knockout (ApoE KO) mice. Although inhibition or deletion of COX-1 retards atherogenesis in ApoE and LDL receptor (LDLR) KOs, the role of COX-2 in atherogenesis remains controversial. Other products of COX-2, such as prostaglandin (PG) I2 and PGE2, may both promote inflammation and restrain the effects of TxA2. Thus, combination with a TP antagonist might reveal an antiinflammatory effect of a COX-2 inhibitor in this disease. We addressed this issue and the role of TxA2 in the promotion and regression of diffuse, established atherosclerosis in Apobec-1/LDLR double KOs (DKOs). METHODS AND RESULTS: TP antagonism with S18886, but not combined inhibition of COX-1 and COX-2 with indomethacin or selective inhibition of COX-2 with Merck Frosst (MF) tricyclic, retards significantly atherogenesis in DKOs. Although indomethacin depressed urinary excretion of major metabolites of both TxA2, 2,3-dinor TxB2 (Tx-M), and PGI2, 2,3-dinor 6-keto PGF(1alpha) (PGI-M), only PGI-M was depressed by the COX-2 inhibitor. None of the treatments modified significantly the increase in lipid peroxidation during atherogenesis, reflected by urinary 8,12-iso-iPF(2alpha)-VI. Combination with the COX-2 inhibitor failed to augment the impact of TP antagonism alone on lesion area. Rather, analysis of plaque morphology reflected changes consistent with destabilization of the lesion coincident with augmented formation of TxA2. Despite a marked effect on disease progression, TP antagonism failed to induce regression of established atherosclerotic disease in this model. CONCLUSIONS: TP antagonism is more effective than combined inhibition of COX-1 and COX-2 in retarding atherogenesis in Apobec-1/LDLR DKO mice, which perhaps reflects activation of the receptor by multiple ligands during disease initiation and early progression. Despite early intervention, selective inhibition of COX-2, alone or in combination with a TP antagonist, failed to modify disease progression but may undermine plaque stability when combined with the antagonist. TP antagonism failed to induce regression of established atherosclerotic disease. TP ligands, including COX-1 (but not COX-2)-derived TxA2, promote initiation and early progression of atherogenesis in Apobec-1/LDLR DKOs but appear unimportant in the maintenance of established disease.

Animals↗

Isolation and characterization of a serine protease from the nematophagous fungus, Lecanicillium psalliotae, displaying nematicidal activity.

Lecanicillium psalliotae produced an extracellular protease (Ver112) which was purified to apparent homogeneity giving a single band on SDS-PAGE with a molecular mass of 32 kDa. The optimum activity of Ver112 was at pH 10 and 70 degrees C (over 5 min). The purified protease degraded a broad range of substrates including casein, gelatin, and nematode cuticle with 81% of a nematode (Panagrellus redivivus) being degraded after treating with Ver112 for 12 h. The protease was highly sensitive to PMSF (1 mM) indicating it to be a serine protease. The N-terminal amino acid residues of Ver112 shared a high degree of similarity with other cuticle-degrading proteases from nematophagous fungi which suggests a role in nematode infection.

Amino Acid Sequence↗

Cardiovascular hazard and non-steroidal anti-inflammatory drugs.

Selective inhibitors of cyclooxygenase (COX)-2 depress prostacyclin (PGI(2)) without a concomitant inhibition of platelet COX-1-derived thromboxane (Tx)A(2). Experiments in gene-deleted mice have shown that ablation of the PGI(2) receptor (the IP) predisposes to an exaggerated response to agonists which elevate blood pressure, accelerate atherogenesis and induce thrombosis. Such a class-based effect would be expected to be modulated by the underlying risk of cardiovascular disease in patients, elements of drug exposure, such as dose, duration of action and duration of dosing, and inter-individual variability of drug response. Five placebo-controlled trials of three structurally distinct selective inhibitors of COX-2 have revealed an increased hazard of myocardial infarction and stroke consistent with a mechanism-based class-specific cardiovascular hazard. Sustained inhibition of platelet TxA(2) by aspirin affords cardiovascular benefit, despite concomitant inhibition of PGI(2). Although there is no information from randomized placebo-controlled trials, traditional non-steroidal anti-inflammatory drugs, such as naproxen, dicofenac and ibuprofen, might differ in their effects of cardiovascular biology.

Animals↗

[Effects of exogenous nitric oxide on photosynthetic characteristics of poplar leaves under water stress].

Nitric oxide (NO) is an active molecule involved in many biological pathways, but its effects on photosynthesis of tree leaves have not been established yet. This paper studied the effects of exogenous NO, sodium nitroprusside (SNP), on the water status, photosynthesis and scavenging enzyme activities in poplar leaves. Different levels of SNP treatments had remarkable effects on the water content of leaves, which increased with increasing SNP levels. When the SNP level exceeded 500 micromol x L(-1), differences in leaf water content were no longer significant between different SNP treatments. Exogenous NO increased the photosynthesis rate, photochemical efficiency of PSII Fv/Fm, and Fm/Fo and Fv/Fo ratios, and the effects decreased with increasing duration of water stress. The SOD and POD activities in poplar leaves were higher in 1 hour water stress treatment than in 3 h treatment. Treating with SNP could markedly increase POD activity, but SOD activity did not change much. POD and SOD activities increased initially, and then decreased with increasing SNP levels. The results indicated that exogenous NO delayed the accumulation of active oxygen by increasing POD and SOD activities, and thereby, alleviated the effects of water stress on photosynthetic organization of poplar leaves.

Nitric Oxide↗

[Stem respiration of Pinus koraiensis in Changbai Mountains].

In this paper, soil respiration chamber, a simple and precise method, was used to measure the stem respiration of trees. LI-6400-09 respiration chamber serving as a system is usually used in soil respiration, but we made polyvinyl chloride (PVC) collar and fixed it on the stem surface to measure the stem respiration. From May to October 2003, the stem respiration of Pinus koraiensis, the dominant tree species in Changbai Mountain, was measured in different time and different places using this technique. Meanwhile, the temperatures in the stems and in the forests were measured. The results showed that the stem respiration rate had a remarkably seasonal tendency with a single peak, the maximum was in August and the minimum was in February. The stem respiration rate had an exponential relationship with stem temperature, and the curve exponential regressions for stem respiration rate and temperature factor of trees with big DBH were better than those with small DBH. The stem respiration in different DBH trees was higher in the south stem face than that in the north stem face, and the variance of respiration rate between south and north decreased with a decrease of DBH trees. During the growing season from May to October, the average maintenance respiration accounted for 63.63% in different DBH trees, and the maintenance respiration contribution to total respiratory consumption increased with increasing DBH, which was 66.76, 73.29% and 50.84%, respectively. The stem respiration Q10 values ranged from 2.56-3.32 in different DBH of trees, and the seasonal tendency for stem R, and Rm in different DBH of trees was obtained by using respiration Q10. Therefore, the differences between different parts of stem and different DBH of trees should be considered in estimating the respiration model in ecosystem.

Air↗

[Effects of simulated water stress on photosynthesis rate and WUE of Fraxinus mandshurica].

This paper studied the photosynthesis characteristics and water use efficiency (WUE) of Fraxinus mandshurica under three years simulated water stresses 85%-100% (CK), 65%-85% (MW) and 45%-65% (LW) of field water-holding capacity. The results showed that in comparing with CK, the photosynthesis rate and WUE were higher in treatment MW, but decreased by 7.26% and 1.13%, respectively in treatment LW, indicating that Fraxinus mandshurica could fully exert its photosynthesis potentiality under long-term medium water stress, and was more resistant to moderate than to critical water stress. In treatment CK, the diurnal change of Pn and WUE was a single and a double peak curve, respectively, while in treatments MW and LW, the diurnal change of Pn was a double peak curve, but that of WUE had no significant peak, which correlated not only to the physiological characteristics of Fraxinus mandshurica under different water stress, but also to the diurnal change of environmental factors.

Ecosystem↗

[Combined local block anesthesia and general anesthesia in cleft lip repairing operation of infants].

OBJECTIVE: Summarizing the value and key point of combined use of local block anesthesia and general anesthesia in cleft lip repairing for infants. METHODS: Local block anesthesia and general anesthesia were combined to use in 120 cleft lip repairing operation of infants using Midazolam, Fentangl, Ketamine, Scoline (or Vecuronium) in intubation, and injecting 0.5% - 1% lidocaine of which contained 1/250 000 adrenalinum. While intubation and operation, BP, P, R, SpO2, T and ECG were observed clearly. After operation, extubation was delayed and breathing oxygen was used for infants with breathing airway infection. RESULTS: While operation, anesthesia of 120 infants was smooth. After operation, the infants regain conscious quickly and no accident occurred. CONCLUSION: For the cleft lip repairing operation to infants, as combined use of local block anesthesia and general anesthesia, anesthesia is smooth, internal environment of body is steady, bleeding is little, regaining consciousness is quick and the infants are safe.

Anesthesia↗

[Effects of exogenous nitric oxide on drought-resistance of poplar].

This paper studied the effects of NO donor sodium nitroprusside (SNP) on the photosynthesis and active oxygen-scavenging enzyme activities of poplar leaves under drought stress. The results showed that SNP had a remarkable positive effect on leaf water content. When the SNP level was > 500 micromol.L(-1), no significant difference in leaf water content was found between SNP treatments. SNP could increase photosynthesis rate, photochemical efficiency of PSII (F(v)/F(m)), and ratios of F(m)/F(o) and F(v)/F(o), but the effects decreased with the prolongation of drought stress. The SOD and POD activities of poplar leaves were higher in short time (1 h) drought stress than in longer time (3 h) one. The activity of POD was increased by SNP, while that of SOD was changed little. With increasing SNP level, the POD and SOD activities first increased and then decreased. The NO donor could retard the accumulation of active oxygen through inducing POD and SOD activities, alleviate the effects of drought stress on photosynthesis, and increase the drought-resistance of poplar.

Disasters↗

Structural mechanism governing cis and trans isomeric states and an intramolecular switch for cis/trans isomerization of a non-proline peptide bond observed in crystal structures of scorpion toxins.

Non-proline cis peptide bonds have been observed in numerous protein crystal structures even though the energetic barrier to this conformation is significant and no non-prolyl-cis/trans-isomerase has been identified to date. While some external factors, such as metal binding or co-factor interaction, have been identified that appear to induce cis/trans isomerization of non-proline peptide bonds, the intrinsic structural basis for their existence and the mechanism governing cis/trans isomerization in proteins remains poorly understood. Here, we report the crystal structure of a newly isolated neurotoxin, the scorpion alpha-like toxin Buthus martensii Karsch (BmK) M7, at 1.4A resolution. BmK M7 crystallizes as a dimer in which the identical non-proline peptide bond between residues 9 and 10 exists either in the cis conformation or as a mixture of cis and trans conformations in either monomer. We also determined the crystal structures of several mutants of BmK M1, a representative scorpion alpha-like toxin that contains an identical non-proline cis peptide bond as that observed in BmK M7, in which residues within or neighboring the cis peptide bond were altered. Substitution of an aspartic acid residue for lysine at residue 8 in the BmK M1 (K8D) mutant converted the cis form of the non-proline peptide bond 9-10 into the trans form, revealing an intramolecular switch for cis-to-trans isomerization. Cis/trans interconversion of the switch residue at position 8 appears to be sequence-dependent as the peptide bond between residues 9 and 10 retains its wild-type cis conformation in the BmK M1 (K8Q) mutant structure. The structural interconversion of the isomeric states of the BmK M1 non-proline cis peptide bond may relate to the conversion of the scorpion alpha-toxins subgroups.

Amino Acid Sequence↗