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Biomedical subjects

Yu Sun

Publications and source records attributed to Yu Sun.

At least 73 records · Page 4Linked to original sources

Effects of cholesterol depletion and increased lipid unsaturation on the properties of endocytic membranes.

Lipid analogs with dialkylindocarbocyanine (DiI) head groups and short or unsaturated hydrocarbon chains (e.g. DiIC(12) and FAST DiI) enter the endocytic recycling compartment efficiently, whereas lipid analogs with long, saturated tails (e.g. DiIC(16) and DiIC(18)) are sorted out of this pathway and targeted to the late endosomes/lysosomes (Mukherjee, S., Soe, T. T., and Maxfield, F. R. (1999) J. Cell Biol. 144, 1271-1284). This differential trafficking of lipid analogs with the same polar head group was interpreted to result from differential partitioning to different types of domains with varying membrane order and/or curvature. Here we investigate the system further by monitoring the trafficking behavior of these lipid analogs under conditions that alter domain properties. There was a marked effect of cholesterol depletion on the cell-surface distribution and degree of internalization of the lipid probes. Furthermore, instead of going to the late endosomes/lysosomes as in control cells, long chain DiI analogs, such as DiIC(16), were sorted to the recycling pathway in cholesterol-depleted cells. We confirmed that this difference was due to a change in overall membrane properties, and not cholesterol levels per se, by utilizing a Chinese hamster ovary cell line that overexpressed transfected stearoyl-CoA desaturase 1, a rate-limiting enzyme in the production of monounsaturated fatty acids. These cells have a decrease in membrane order because they contain a much larger fraction of unsaturated fatty acids. These cells showed alteration of DiI trafficking very similar to cholesterol-depleted cells. By using cold Triton X-100 extractability of different lipids as a criterion to determine the membrane properties of intracellular organelles, we found that the endocytic recycling compartment has abundant detergent-resistant membranes, in contrast to the late endosomes and lysosomes.

Animals↗

Autofocusing in computer microscopy: selecting the optimal focus algorithm.

Autofocusing is a fundamental technology for automated biological and biomedical analyses and is indispensable for routine use of microscopes on a large scale. This article presents a comprehensive comparison study of 18 focus algorithms in which a total of 139,000 microscope images were analyzed. Six samples were used with three observation methods (brightfield, phase contrast, and differential interference contrast (DIC)) under two magnifications (100x and 400x). A ranking methodology is proposed, based on which the 18 focus algorithms are ranked. Image preprocessing was also conducted to extensively reveal the performance and robustness of the focus algorithms. The presented guidelines allow for the selection of the optimal focus algorithm for different microscopy applications.

Algorithms↗

REP3-mediated silencing in Saccharomyces cerevisiae.

In yeast the Sir proteins and Rap1p are key regulators of transcriptional silencing at telomeres and the silent mating-type loci. Rap1 and Sir4 also possess anchoring activity; the rotation of plasmids bound by Sir4 or Rap1 is constrained in vivo, and Rap1 or Sir4 binding can also correct the segregation bias of plasmids lacking centromeres. To investigate the mechanistic link between DNA anchoring and regulation of transcription, we examined the ability of a third defined anchor in yeast, the 2micro circle REP3 segregation element, to mediate transcriptional silencing. We find that placement of the REP3 sequence adjacent to the HML locus in a strain deleted for natural silencer sequences confers transcriptional repression on HML. This repression requires the Sir proteins and is decreased in strains lacking the REP3-binding factors Rep1 and Rep2. The yeast cohesin complex associates with REP3; we show that REP3 silencing is also decreased in strains bearing a mutated allele of the MCD1/SCC1 cohesin gene. Conventional silencing is increased in some strains lacking the 2micro circle and decreased in strains overexpressing the Rep1 and Rep2 proteins, suggesting that the Rep proteins antagonize conventional silencing.

Base Sequence↗

[Synthesis of polymeric drug nanomicrospheres containing probenecid].

Nonsteroidal antiinflammatory drug, probenecid, was covalently linked with 2-hydroxyethyl methacrylate (HEMA). The drug linked HEMA(abbreviated as HP) can be copolymerized with methy methacrylate (MMA) to obtain polymeric drug nanomicrospheres in ethanol/water system. Polymers were characterized with 1H-NMR, FTIR, GPC and TEM. The results showed that probenecid was linked with HEMA by ester bond, the microspheres were composed of copolymer of HP and MMA, whose statistical average diameters were (90 +/- 5) nm, containing 47.4% HP, and drug content was high.

Adjuvants, Pharmaceutic↗

Expression of liver X receptor target genes decreases cellular amyloid beta peptide secretion.

A hallmark of Alzheimer's disease is the deposition of plaques of amyloid beta peptide (Abeta) in the brain. Abeta is thought to be formed from the amyloid precursor protein (APP) in cholesterol-enriched membrane rafts, and cellular cholesterol depletion decreases Abeta formation. The liver X receptors (LXR) play a key role in regulating genes that control cellular cholesterol efflux and membrane composition and are widely expressed in cells of the central nervous system. We show that treatment of APP-expressing cells with LXR activators reduces the formation of Abeta. LXR activation resulted in increased levels of the ATP-binding cassette transporter A1 (ABCA1) and stearoyl CoA desaturase, and expression of these genes individually decreased formation of Abeta. Expression of ABCA1 led to both decreased beta-cleavage product of APPSw (i.e. C99 peptide) and reduced gamma-secretase-cleavage of C99 peptide. Remarkably, these effects of ABCA1 on APP processing were independent of cellular lipid efflux. LXR and ABCA1-induced changes in membrane lipid organization had favorable effects on processing of APP, suggesting a new approach to the treatment of Alzheimer's disease.

ATP Binding Cassette Transporter 1↗

Blood mercury levels in US children and women of childbearing age, 1999-2000.

CONTEXT: Humans are exposed to methylmercury, a well-established neurotoxin, through fish consumption. The fetus is most sensitive to the adverse effects of exposure. The extent of exposure to methylmercury in US women of reproductive age is not known. OBJECTIVE: To describe the distribution of blood mercury levels in US children and women of childbearing age and the association with sociodemographic characteristics and fish consumption. DESIGN AND SETTING: The 1999-2000 data from the National Health and Nutrition Examination Survey, a cross-sectional survey of the noninstitutionalized US population. PARTICIPANTS: In 1999-2000, 1250 children aged 1 to 5 years and 2314 women aged 16 to 49 years were selected to participate in the survey. Household interviews, physical examinations, and blood mercury levels assessments were performed on 705 children (56% response rate) and 1709 women (74% response rate). MAIN OUTCOME MEASURE: Blood concentration of total mercury. RESULTS: Blood mercury levels were approximately 3-fold higher in women compared with children. The geometric mean concentration of total blood mercury was 0.34 micro g/L (95% confidence interval [CI], 0.30-0.39 microg/L) in children and 1.02 microg/L (95% CI, 0.85-1.20 microg/L) in women. Geometric mean mercury levels were almost 4-fold higher among women who ate 3 or more servings of fish in the past 30 days compared with women who ate no fish in that period (1.94 microg/L vs 0.51 microg/L; P<.001). CONCLUSIONS: Measures of mercury exposure in women of childbearing age and young children generally fall below levels of concern. However, approximately 8% of women had concentrations higher than the US Environmental Protection Agency's recommended reference dose (5.8 microg/L), below which exposures are considered to be without adverse effects. Women who are pregnant or who intend to become pregnant should follow federal and state advisories on consumption of fish.

Adolescent↗

Extracellular ATP inhibits root gravitropism at concentrations that inhibit polar auxin transport.

Raising the level of extracellular ATP to mM concentrations similar to those found inside cells can block gravitropism of Arabidopsis roots. When plants are grown in Murashige and Skoog medium supplied with 1 mM ATP, their roots grow horizontally instead of growing straight down. Medium with 2 mM ATP induces root curling, and 3 mM ATP stimulates lateral root growth. When plants are transferred to medium containing exogenous ATP, the gravity response is reduced or in some cases completely blocked by ATP. Equivalent concentrations of ADP or inorganic phosphate have slight but usually statistically insignificant effects, suggesting the specificity of ATP in these responses. The ATP effects may be attributable to the disturbance of auxin distribution in roots by exogenously applied ATP, because extracellular ATP can alter the pattern of auxin-induced gene expression in DR5-beta-glucuronidase transgenic plants and increase the response sensitivity of plant roots to exogenously added auxin. The presence of extracellular ATP also decreases basipetal auxin transport in a dose-dependent fashion in both maize (Zea mays) and Arabidopsis roots and increases the retention of [(3)H]indole-3-acetic acid in root tips of maize. Taken together, these results suggest that the inhibitory effects of extracellular ATP on auxin distribution may happen at the level of auxin export. The potential role of the trans-plasma membrane ATP gradient in auxin export and plant root gravitropism is discussed.

Adenosine Triphosphate↗

Disruption of apyrases inhibits pollen germination in Arabidopsis.

In Arabidopsis, we previously identified two highly similar apyrases, AtAPY1 and AtAPY2. Here, T-DNA knockout (KO) mutations of each gene were isolated in a reverse genetic approach. The single KO mutants lacked a discernible phenotype. The double KO mutants, however, exhibited a complete inhibition of pollen germination, and this correlated with positive beta-glucuronidase staining in the pollen of apyrase promoter:beta-glucuronidase fusion transgenic lines. The vast majority of the pollen grains of these mutants were identical to wild type in size, shape, and nuclear state and were viable as assayed by metabolic activity and plasma membrane integrity. Complementation with either AtAPY1 or AtAPY2 cDNA rescued pollen germination, confirming that the phenotype was apyrase specific. Despite the redundancy of the two apyrases in rescue potential, transmission analyses suggested a greater role for AtAPY2 in male gamete success. The effect of mutant apyrase on the transmission through the female gametophyte was only marginal, and embryo development appeared normal in the absence of apyrases. The male-specific double KO mutation is fully penetrant and shows that apyrases play a crucial role in pollen germination.

Apyrase↗

Mechanical property characterization of mouse zona pellucida.

Previous intracytoplasmic sperm injection (ICSI) studies have indicated significant variation in ICSI success rates among different species. In mouse ICSI, the zona pellucida (ZP) undergoes a "hardening" process at fertilization in order to prevent subsequent sperm from penetrating. There have been few studies investigating changes in the mechanical properties of mouse ZP post fertilization. To characterize mouse ZP mechanical properties and quantitate the mechanical property differences of the ZP before and after fertilization, a microelectromechanical systems-based multiaxis cellular force sensor has been developed. A microrobotic cell manipulation system employing the multiaxis cellular force sensor is used to conduct mouse ZP force sensing, establishing a quantitative relationship between applied forces and biomembrane structural deformations on both mouse oocytes and embryos. An analytical biomembrane elastic model is constructed to describe biomembrane mechanical properties. The characterized elastic modulus of embryos is 2.3 times that of oocytes, and the measured forces for puncturing embryo ZP are 1.7 times those for oocyte ZP. The technique and model presented in this paper can be applied to investigations into the mechanical properties of other biomembranes, such as the plasma membrane of oocytes or other cell types.

Animals↗

The hemodynamic effects of internal carotid artery stenting: a study with color-coded duplex sonography.

BACKGROUND: Stenting has been used as an alternative treatment for patients with internal carotid artery (ICA) stenosis. Color-coded duplex sonography (CDS) is able to measure not only the prestenting stenosis but also the poststenting hemodynamic changes. The purpose of this study was to quantify, using CDS, the hemodynamic changes after ICA stenting. METHODS: Both symptomatic and asymptomatic patients were included in this study. The degree of ICA stenosis before stenting was required to be more than 50%. Thirty-two treated ICAs were included to compare the prestenting and poststenting CDS findings, including the diameter and cross-sectional area of the lumen, the flow peak systolic and end-diastolic velocities, the resistivity index and the amount of flow in bilateral extracranial carotid and vertebral arteries. RESULTS: After stenting, the turbulent flow pattern in the stenotic ICA recovered to laminar flow, and the reversed ophthalmic flow direction normalized. Of the CDS parameters applied to evaluate the effect of stenting on ICA stenosis, the diameter, residual area, peak systolic velocity, diastolic velocity and the ration of systolic flow velocity ratio in the ICA to that in the common carotid artery (CCA) were altered significantly. The mean area and residual area of these stenotic ICAs showed increases of 24% (p = 0.005) and 84% (p = 0.001) after ICA stenting, respectively. The mean peak systolic flow velocity significantly decreased by 71%. The mean diastolic flow velocity also significantly decreased (by 77%). Both the systolic and diastolic velocities of the ipsilateral CCA significantly increased after stenting. The amount of flow in the contralateral ICA decreased significantly after stenting. The change in the amount of flow in the vertebral arteries after ICA stenting was insignificant. CONCLUSIONS: The results of this CDS study clearly demonstrated the hemodynamic changes after ICA stenting. The carotid stenting significantly changed the ICA flow pattern, diameter, residual area, peak systolic velocity and ICA to CCA velocity ratio.

Aged↗

[Replication of animal model and pathological study of delayed multiple organ dysfunction syndrome in mice].

OBJECTIVE: To replicate a model of delayed multiple organ dysfunction syndrome (MODS) in mice. METHODS: Kunming mice of 6-8 week age were randomly divided into normal control group and experimental group. They were sacrificed on days 0 to 2, days 3 to 7, days 8 to 12. Symptoms and signs, survival rate, organ function parameters and pathological changes in main organs were observed in mice of all groups. RESULTS: Eight days after zymosan administration, animals showed MODS-like changes. Plasma level of alanine aminotransferase(ALT), blood urea nitrogen(BUN) and creatinine(Cr) were increased and severe pathological lesions were observed in tissues of the lung, liver, heart, kidney and gut, etc. CONCLUSION: A delayed model of MODS is replicated in mice by intraperitoneal injection of zymosan.

Animals↗

[Structure and heterogeneity of urban vegetation landscape in Shenyang].

Studies on the structure and heterogeneity of urban vegetation landscape in Shenyang city showed that the most vegetation patches were in the street corner, accounted for more than 50% of the total vegetation patch, and their area was only 4.45% of the total vegetation area. In terms of the size of the patches, the average area of shelter vegetation and park vegetation was 66.97 hm2 and 59.31 hm2, respectively, while that of street corner vegetation and garden vegetation was 0.71 hm2 and 0.38 hm2, respectively. Street corner vegetation had the highest index of landscape diversity, while park vegetation had the lowest one. In the seven districts of Shenyang city, all types of vegetation had a small landscape dominance and evenness, but patch vegetation had a more than 10 times of landscape dominance than corridor vegetation, indicating that there was somewhat imbalance in the allocation of different vegetation patch types. It's suggested that the quantity of patch vegetation should be increased, and the public vegetation should be distributed evenly. Increasing vegetation corridor is also important because it can link the downtown area to the suburb natural vegetation ecosystems. For example, the South Canal Belt Park of Shenyang is a good vegetation corridor, which can beautify Shenyang city, discharge sewage, drain flood, and improve microclimate.

Agriculture↗

[Dust absorption effect of urban conifers in northeast China].

Dust pollution is much heavier in winter than in other seasons in the cities of Northeast China, because the urban heating system consumes mainly coal as energy resources. Deciduous trees can hardly absorb dust because of their defoliation, and hence, urban conifer trees become more important in dust absorption in winter. This paper studied the dust absorption ability of 7 conifers under the same and different dust pollution status in Shenyang city, Northeast China. The results showed that the dust absorption ability of conifers was decreased in the order of Abies holophilla > Picea mongolica > P. koraiensis > Taxus cupidata > Pinus bungeana > P. armandi > P. tabulaeformis. Different conifers had different surface structures. Pinus bungeana, P. armandi and P. tabulaeformis had smooth surfaces, their cells and stomata arranged in order, and hence, their dust absorption ability was poor. P. koraiensis, Abies holophilla and Taxus cupidata had coarse surfaces, and their cells and stomata arranged out of order. There were even many tubercular things on the surface of P. koraiensis, and hence, their dust absorption ability was stronger. The dust absorption ability of conifers was related the shape of their leaf sections. The upper leaf surface of Pinus bungeana and P. tabulaeformis was arc, not opted to absorb the dust. The leaf section of P. armandi was prism, and its upper surface was narrow, and hence, its dust absorption ability was also poor. The leaves of Picea mongolica and P. koraiensis had four edges, their upper surfaces were broader and flatter than the former three species, and hence, they had stronger dust absorption ability. The leaf section's shape of Abies holophilla and Taxus cupidata was also broad and flat, which made the dust absorption ability of the two latter's was stronger than other three Pinus species and two Picea species.

Absorption↗

Stearoyl-CoA desaturase inhibits ATP-binding cassette transporter A1-mediated cholesterol efflux and modulates membrane domain structure.

Liver X receptor/retinoid X receptor (LXR/RXR) transcription factors have been found to induce a number of genes involved in the regulation of cellular cholesterol efflux, including the ATP-binding cassette transporter A1 (ABCA1), which mediates the active efflux of cellular cholesterol and phospholipids to extracellular acceptors, such as apolipoprotein A-I (apoA-I). In a screen for macrophage LXR/RXR target genes, we identified stearoyl-CoA desaturases 1 and 2 (Scd1 and Scd2), and subsequently tested the hypothesis that SCD activity might modulate cellular cholesterol efflux. In HEK 293 cells co-transfection of ABCA1 with either SCD1 or SCD2 inhibited ABCA1-mediated cholesterol efflux but not phospholipid efflux. In Chinese hamster ovary (CHO) cells with moderate stable overexpression of SCD1, cholesterol efflux to apoA-I was inhibited by 73%, whereas phospholipid efflux and ABCA1 protein levels were unchanged. In contrast, cholesterol efflux to HDL(2), which is not dependent on ABCA1, was increased 2-fold in CHO-SCD1 cells. The effect of SCD on cholesterol efflux to apoA-I was independent of acyl-CoA:cholesterol acyltransferase (ACAT) activity. SCD activity led to an increased content of plasma membrane monounsaturated fatty acids (18:1) at the expense of saturated fatty acids (18:0). As shown by confocal microscopy, SCD overexpression led to a decrease of Triton X-100-resistant domains in the plasma membrane, indicating a decrease in membrane-ordered regions. The data suggest that SCD changes membrane organization and depletes a specific pool of membrane cholesterol supporting ABCA1-mediated efflux, whereas increasing availability of cholesterol for passive efflux by HDL(2). ABCA1-mediated cholesterol and phospholipid efflux may be uncoupled in pathological states associated with high SCD activity, as in hyperinsulinemic obese mice, or in animals treated with LXR activators.

ATP-Binding Cassette Transporters↗

Air-stable, electron-deficient Fe(II) catalytic porphyrins. Characterization and molecular structures of rare high spin Fe(II) hexacoordinated porphyrins.

The synthesis, characterization, and molecular structures of the first air-stable, hexacoordinated high spin Fe(II) porphyrins (1) with axial alcohols are reported (1 = Fe(II) meso-tetrakis(o-dichlorophenyl)-beta-octanitroporphyrin). The structure of 1 with two axial waters is also presented. The very different conformations and metrics observed with the two types of ligands illustrate the acute interplay between ligands, conformations, and spin states in Fe porphyrins.

Journal Article↗

Mechanism of glutamate receptor desensitization.

Ligand-gated ion channels transduce chemical signals into electrical impulses by opening a transmembrane pore in response to binding one or more neurotransmitter molecules. After activation, many ligand-gated ion channels enter a desensitized state in which the neurotransmitter remains bound but the ion channel is closed. Although receptor desensitization is crucial to the functioning of many ligand-gated ion channels in vivo, the molecular basis of this important process has until now defied analysis. Using the GluR2 AMPA-sensitive glutamate receptor, we show here that the ligand-binding cores form dimers and that stabilization of the intradimer interface by either mutations or allosteric modulators reduces desensitization. Perturbations that destabilize the interface enhance desensitization. Receptor activation involves conformational changes within each subunit that result in an increase in the separation of portions of the receptor that are linked to the ion channel. Our analysis defines the dimer interface in the resting and activated state, indicates how ligand binding is coupled to gating, and suggests modes of dimer dimer interaction in the assembled tetramer. Desensitization occurs through rearrangement of the dimer interface, which disengages the agonist-induced conformational change in the ligand-binding core from the ion channel gate.

Allosteric Regulation↗