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Biomedical subjects

Yue Chen

Publications and source records attributed to Yue Chen.

At least 37 records · Page 2Linked to original sources

HDAC1 acetylation is linked to progressive modulation of steroid receptor-induced gene transcription.

Although histone deacetylases (HDACs) are generally viewed as corepressors, we show that HDAC1 serves as a coactivator for the glucocorticoid receptor (GR). Furthermore, a subfraction of cellular HDAC1 is acetylated after association with the GR, and this acetylation event correlates with a decrease in promoter activity. HDAC1 in repressed chromatin is highly acetylated, while the deacetylase found on transcriptionally active chromatin manifests a low level of acetylation. Acetylation of purified HDAC1 inactivates its deacetylase activity, and mutation of the critical acetylation sites abrogates HDAC1 function in vivo. We propose that hormone activation of the receptor leads to progressive acetylation of HDAC1 in vivo, which in turn inhibits the deacetylase activity of the enzyme and prevents a deacetylation event that is required for promoter activation. These findings indicate that HDAC1 is required for the induction of some genes by the GR, and this activator function is dynamically modulated by acetylation.

Acetylation↗

Association between maternal exposure to ambient air pollutants during pregnancy and fetal growth restriction.

Previous research demonstrated consistent associations between ambient air pollution and emergency room visits, hospitalizations, and mortality. Effect of air pollution on perinatal outcomes has recently drawn more attention. We examined the association between intrauterine growth restriction (IUGR) among singleton term live births and sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and fine particles (PM2.5) present in ambient air in the Canadian cities of Calgary, Edmonton, and Montreal for the period 1985-2000. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for IUGR, based on average daily levels of individual pollutants over each month and trimester of pregnancy after adjustment for maternal age, parity, infant gender, season, and city of residence. A 1 ppm increase in CO was associated with an increased risk of IUGR in the first (OR=1.18; 95% CI 1.14-1.23), second (OR=1.15; 95% CI 1.10-1.19) and third (OR=1.19; 95% CI 1.14-1.24) trimesters of pregnancy, respectively. A 20 ppb increase in NO2 (OR=1.16; 95% CI 1.09-1.24; OR=1.14; 95% CI 1.06--1.21; and OR=1.16; 95% CI 1.09-1.24 in the first, second, and third trimesters) and a 10 mug/m3 increase in PM2.5 (OR=1.07; 95% CI 1.03-1.10; OR=1.06; 95% CI 1.03-1.10; and OR=1.06; 95% CI 1.03-1.10) were also associated with an increased risk of IUGR. Consistent results were found when ORs were calculated by month rather than trimester of pregnancy. Our findings add to the emerging body of evidence that exposure to relatively low levels of ambient air pollutants in urban areas during pregnancy is associated with adverse effects on fetal growth.

Air Pollutants↗

An intimate collaboration between peroxisomes and lipid bodies.

Although peroxisomes oxidize lipids, the metabolism of lipid bodies and peroxisomes is thought to be largely uncoupled from one another. In this study, using oleic acid-cultured Saccharomyces cerevisiae as a model system, we provide evidence that lipid bodies and peroxisomes have a close physiological relationship. Peroxisomes adhere stably to lipid bodies, and they can even extend processes into lipid body cores. Biochemical experiments and proteomic analysis of the purified lipid bodies suggest that these processes are limited to enzymes of fatty acid beta oxidation. Peroxisomes that are unable to oxidize fatty acids promote novel structures within lipid bodies ("gnarls"), which may be organized arrays of accumulated free fatty acids. However, gnarls are suppressed, and fatty acids are not accumulated in the absence of peroxisomal membranes. Our results suggest that the extensive physical contact between peroxisomes and lipid bodies promotes the coupling of lipolysis within lipid bodies with peroxisomal fatty acid oxidation.

Acyl-CoA Oxidase↗

Establishment of correlation between in vitro enzyme binding potency and in vivo pharmacological activity: application to liver glycogen phosphorylase a inhibitors.

In drug discovery, establishing a correlation between in vitro potency and in vivo activity is critical for the validation of the selected target and for developing confidence in the in vitro screening strategy. The present study developed a competition equilibrium dialysis assay using a 96-well dialysis technique to determine the intrinsic Kd for 13 inhibitors of human liver glycogen phosphorylase a (GPa) in the presence of liver homogenate to mimic the physiological environment. The results provided evidence that binding of an inhibitor to GPa was affected by extra cofactors present in the liver homogenate. A good correlation was demonstrated between the in vitro Kd determined under liver homogenate environment and free liver concentration of an inhibitor at the minimum efficacious dose in diabetic ob/ob mice. This study revealed important elements (such as endogenous cofactors missing from the in vitro assay and free concentration at the target tissue) that contributed to a better understanding of the linkage between in vitro and in vivo activity. The approach developed here may be applied to many drugs in pharmacology studies in which the correlation between in vitro and in vivo activities for the target tissue (such as solid tumors, brain, and liver) is critical.

Animals↗

Chronic sinusitis and arterial hypertension in a national population health survey.

BACKGROUND: To determine if sinusitis is associated with arterial hypertension in the Canadian population. METHODS: Complex survey design incorporating stratification, multiple stages of selection, and unequal probabilities of selection of respondents. Cross-sectional data from 52,992 subjects (25,324 males and 27,668 females) 20-64 years of age who participated in the second cycle of the National Population Health Survey (NPHS), conducted in 1996-1997. All these individuals were asked if they had certain chronic health conditions, that had lasted or were expected to last 6 months or more, including sinusitis and high blood pressure. RESULTS: Overall, males with sinusitis were just over 2% more likely to have hypertension (9.3% vs. 7.1%) whereas the difference was 4% for women (11.8% vs. 7.6%). Adjusted for age, region, habitation, immigrant status, household size, number of bedrooms, income adequacy, education level, smoking status, alcohol consumption, regular exercise and body mass index, the adjusted odds ratio for females was 1.42 (95% CI 1.04, 1.95). CONCLUSIONS: Reported sinusitis is associated with hypertension but only in women. Mechanisms linking upper respiratory disorders to hypertension merit investigation.

Adult↗

Obesity and leisure time physical activity among Canadians.

BACKGROUND: The association between physical activity and obesity are age and sex related. METHODS: The analysis was based on data from 81,512 Canadians aged 20 to 64 years who participated in the Canadian Community Health Survey conducted in 2000-01. Information collected included body mass index (BMI:<25.0 kg/m(2) (normal weight); 25.0-29.9 kg/m(2) (overweight); and 30.0+ kg/m(2) (obese)) and energy expenditure (EE) calculated based on the frequency and duration of leisure time physical activity (LTPA) and its value of metabolic energy cost. RESULTS: Obese men and both obese and overweight women had lower EE values compared with those with normal weight. Overweight men 30 to 49 years of age were more active than men with normal weight. Average EE values decreased with age. Overall, 53.2% of men and 57.1% of women were inactive (EE<1.5 kcal/kg/day). In obese men and women, the corresponding prevalences were 59.7% and 71.4%, respectively. The prevalence of physical inactivity increased with increasing BMI in women and there was no "dose-effect" relationship in men. CONCLUSIONS: Obese Canadians are less active, but overweight men tend to be more active than those with normal weight. The variation in the associations across age and sex groups suggests that intervention program development should take age and sex into consideration.

Adult↗

Magnesium deficiency enhances hydrogen peroxide production and oxidative damage in chick embryo hepatocyte in vitro.

Magnesium deficiency and oxidative stress have been identified as correlative factors in many diseases. The origin of free radicals correlated with oxidative damage resulting from Mg-deficiency is unclear at the cellular level. To investigate whether hydrogen peroxide (H2O2) is associated in the oxidative stress induced by Mg-deficiency, the effect of Mg2+ deficiency (0, 0.4, 0.7 mM) on the metabolism of H2O2 was investigated in cultured chick embryo hepatocytes. After being cultured in the media with various concentrations of Mg2+ for 1, 2, 4, 6 and 10 days, parameters of H2O2 production, catalase activity, lipid peroxidation, intracellular total Mg and cell viability were analyzed. Results demonstrated that long-term incubation of chick embryo hepatocyte in extracellular Mg2+-deprivative and Mg2+-deficient (0.4 mM) states significantly enhanced the production of H2O2 (approximately twofold, respectively) and lipid peroxidation in the cell cultures, while decreasing the cell viability. Additionally, the reversing action of Mg2+ re-added to 1.0 mM and the partial reversing action of dimethylthiourea suggested that (i) [Mg2+]e deficiency induced the increase of H2O2 production, (ii) [Mg2+]e deficiency decreased catalase activity in chick embryo hepatocyte in vitro, subsequently causing oxidative stress and cell peroxidative damage.

Animals↗

Substrate and functional diversity of lysine acetylation revealed by a proteomics survey.

Acetylation of proteins on lysine residues is a dynamic posttranslational modification that is known to play a key role in regulating transcription and other DNA-dependent nuclear processes. However, the extent of this modification in diverse cellular proteins remains largely unknown, presenting a major bottleneck for lysine-acetylation biology. Here we report the first proteomic survey of this modification, identifying 388 acetylation sites in 195 proteins among proteins derived from HeLa cells and mouse liver mitochondria. In addition to regulators of chromatin-based cellular processes, nonnuclear localized proteins with diverse functions were identified. Most strikingly, acetyllysine was found in more than 20% of mitochondrial proteins, including many longevity regulators and metabolism enzymes. Our study reveals previously unappreciated roles for lysine acetylation in the regulation of diverse cellular pathways outside of the nucleus. The combined data sets offer a rich source for further characterization of the contribution of this modification to cellular physiology and human diseases.

Acetylation↗

Development of nocturnal urinary control in Chinese children younger than 8 years old.

OBJECTIVES: To estimate the development of nocturnal urinary control (NUC) with age in Chinese children younger than 8 years of age using cross-sectional and retrospective surveys. METHODS: We used a cross-sectional survey of 4754 children (1 to 8 years old), a retrospective investigation of 2745 children younger than 9 years old, and an anonymous questionnaire of 8222 children 9 to 18 years old . The children without NUC were subdivided into infant (1 to 3 years old), preschool age (4 to 6 years old), and primary school (7 to 8 years old) groups. RESULTS: The response rate to the cross-sectional and retrospective surveys was 90% and 89%, respectively. In the cross-sectional survey, the prevalence of children attaining NUC was 52% for those younger than 2 years of age, 76% for those aged 2 to 3 years, and 93% at age 8. Girls were more likely than boys to acquire NUC earlier. In the retrospective survey, the prevalence of children attaining NUC before age 2 was 17% and was 72% for those aged 2 to 3 years, and 98% by age 8. The proportion of nonmonosymptomatic bedwettings in children without NUC was 14%. Arousal difficulty and a positive family history were found in 67% and 11% of children with nocturnal wetting, respectively. The severity of bedwetting and arousal difficulty was significantly greater in infants than in preschool and school-age children. CONCLUSIONS: The results from the cross-sectional and retrospective surveys showed that the most important period of attaining NUC is 2 to 3 years of age. Nearly 90% of children attained NUC by the age of 5.

Adolescent↗

A clean, more efficient method for in-solution digestion of protein mixtures without detergent or urea.

Proteolytic digestion of a complicated protein mixture from an organelle or whole-cell lysate is usually carried out in a dilute solution of a denaturing buffer, such as 1-2 M urea. Urea must be subsequently removed by C18 beads before downstream analysis such as HPLC/MS/MS or complete methylation followed by IMAC isolation of phosphopeptides. Here we describe a procedure for digesting a complicated protein mixture in the absence of denaturants. Proteins in the mixture are precipitated with trichloroacetic acid/acetone for denaturation and salt removal and resuspended in NH4HCO3 buffer. After trypsinolysis, the resulting peptides are not contaminated by urea or other nonvolatile salts and can be dried in a SpeedVac to remove NH4HCO3. When this protocol was applied to an extract of A431 cells, 96.8% of the tryptic peptides were completely digested (i.e., had no missed cleavage sites), in contrast to 87.3% of those produced by digestion in urea buffer. We successfully applied this digestion method to analysis of the phosphoproteome of adiposomes from HeLa cells, identifying 33 phosphorylation sites in 28 different proteins. Our digestion method avoids the need to remove urea before HPLC/MS/MS analysis or methylation and IMAC, increasing throughput while reducing sample loss and contamination from sample handling. We believe that this method should be valuable for proteomics studies.

Amino Acid Sequence↗

Association between air pollution and multiple respiratory hospitalizations among the elderly in Vancouver, Canada.

Recurrent events, such as repeated hospital admissions for the same health outcome, occur frequently in environmental health studies. In this study, we conducted an analysis of data on repeated respiratory hospitalizations among the elderly in Vancouver, Canada, for the period of June 1, 1995, to March 31, 1999, using a new method proposed by (Dewanji and Moolgavkar 2000, 2002) for recurrent events, and compared it with some traditional methods. In particular, we assessed the impact of ambient gaseous (SO2, NO2, CO, and O3) and particulate pollutants (PM10, PM2.5, and PM10-2.5) as well as the coefficient of haze (CoH) on recurrent respiratory hospital admissions. Using the new procedure, significant associations were found between admissions and 3-day, 5-day, and 7-day moving averages of the ambient SO2 concentrations, with the strongest association observed at the 7-day lag (RR = 1.044, 95% CI: 1.018-1.070). We also found PM10-2.5 for 3-day and 5-day lag to be significant, with the strongest association at 5-day lag (RR = 1.020, 95% CI: 1.001-1.039). No significant associations with admission were found with current day exposure.

Aged↗

Characterization of the gp120 of circulating HIV type 1 in a group of infected Chinese blood/plasma donors with asymptomatic and symptomatic stages of the disease.

The C2-V5 regions of the HIV envelope gene were cloned and sequenced from DNA samples of four asymptomatic and five AIDS patients from a cohort of HIV-1-infected Chinese plasma and blood donors. Sequence analysis revealed that regardless of the stage of disease, all the patient's HIV-1 belonged to either clade B' or circulating recombinant form 15 (CRF15) subtype. However, since these blood donors were infected at a time when circulating CRF15 was not known in that region, it is likely these HIV-1 types belong to clade B'. However, the C2-V5 sequences from AIDS patients clustered differently in the phylogenetic tree than those present in asymptomatic patients and showed a significantly higher divergence and lower diversity compared to those from asymptomatic patients. In addition, more syncytia-inducing viral genotypes were present in AIDS patients than in asymptomatic patients. These results contribute to a better understanding of the pathogenesis of circulating HIV-1 in infected Chinese plasma and blood donors, warrant additional investigation of the possible presence of CRF15 in Chinese blood donors, and may have important implications in the future design of therapeutic strategies for treating these infected patients.

Asian People↗

Two patterns of leaf photosynthetic response to irradiance transition from saturating to limiting one in some plant species.

Plants often regulate the amount and size of light-harvesting antenna (LHCII) to maximize photosynthesis at low light and avoid photodamage at high light. Gas exchange, 77 K chlorophyll fluorescence, photosystem II (PSII) electron transport as well as LHCII protein were measured in leaves irradiated at different light intensities. After irradiance transition from saturating to limiting one leaf photosynthetic rate in some species such as soybean and rice declined first to a low level, then increased slowly to a stable value (V pattern), while in other species such as wheat and pumpkin it dropped immediately to a stable value (L pattern). Saturating pre-irradiation led to significant declines of both 77 K fluorescence parameter F685/F735 and light-limited PSII electron transport rate in soybean but not in wheat leaves, indicating that some LHCIIs dissociate from PSII in soybean but not in wheat leaves. The L pattern of LHCII-decreased rice mutant and the V pattern of its wild type demonstrate that the V pattern is linked to dissociation/reassociation of some LHCIIs from/to PSII.

Adaptation, Physiological↗

The association between obesity and asthma is stronger in nonallergic than allergic adults.

STUDY OBJECTIVE: To determine the modifying effects of sex and allergy history on the association between body mass index (BMI) and asthma prevalence. DESIGN: Cross-sectional study of 86,144 Canadians who were 20 to 64 years of age in 2000-2001. SETTING: A national survey. MEASUREMENTS AND ANALYSIS: Self-reported asthma, allergy history, height, and weight. Logistic regression analysis was used to detect effect modification and to adjust for covariates. Population weight and design effects associated with complex survey design were taken into consideration. RESULTS: The adjusted odds ratios (ORs) for obesity associated with asthma was 1.85 (95% confidence interval [CI], 1.65 to 2.07) for women and 1.21 (95% CI, 1.05 to 1.40) for men. One unit of increased BMI was associated with an approximate 6% increase in asthma risk in women, and 3% in men. A stronger association between obesity and asthma was observed in nonallergic women than in allergic women, with the adjusted ORs being 2.53 (95% CI, 2.11 to 3.04) and 1.57 (95% CI, 1.36 to 1.82), respectively. For men, the corresponding ORs were 1.30 (95% CI, 1.05 to 1.62) and 1.18 (95% CI, 0.98 to 1.53), respectively. CONCLUSIONS: Obesity is likely to have a larger effect on nonallergic asthma. The greater prevalence of nonallergic asthma in women may explain the stronger obesity-asthma association seen in women compared with men and children who have a greater prevalence of allergic asthma.

Adult↗

[Clinically anatomic study on the relation between the form of pleural cupula and its surrounding commonly-used acupoints].

OBJECTIVE: To explore the relation of the form of pleural cupula of the normal adult with safety of acupuncture at commonly-used acupoints around the pleural cupula. METHODS: The safe depth for the commonly-used acupoints around the pleural cupula and the relation with the form of pleural cupula were investigated in 46 adult corpses with small Kirschner wire location and arrangement dissection. RESULTS: The width of the pleural cupula projection equal to clavicle medial 1/3 accounted for 32. 6% of all the corpses, and the width of the pleural cupula projection more than clavicle medial 1/3 accounted for 59. 8% of all the corpses, the width of the pleural cupula projection less than clavicle medial 1/3 and pleural cupula medial margin located at the sternoclavicular joint medial accounted for 7.6% of all the corpses. The observed points such as Tiantu (CV 22), Qishe (ST 11), Jianjing (GB 21), Dingchuan (EX-B1), Dazhu (BL 11) which were considered be not related to the pleural cupula. When acupuncture is carried out according to criteria of acupoint location and needling direction, and the needle exceeded a limit, the pleural menbrane will be broken and induce destruction. CONCLUSION: Position and form of the pleural cupula have anatomical relation to acupuncture accident for needling the points around the superior pleural cupula, which should be played attention to.

Acupuncture Points↗

[Isolation of bone marrow-derived rat osteoclast-like cells with the digestion of trypsin].

OBJECTIVE: To obtain highly enriched osteoclasts in vitro. METHODS: The bone marrow cells of 1-day, 12-day, 24-day and 36-day old Sprague-Dawley (SD) rats were separately cultured with the presence of 1,25-(OH)2D3 and dexamethasone, and the osteoclast-like cells were identified by Trap staining and scanning electron microscope observation and were purified by trypsin digestion. The count of Trap positive osteoclast-like cells was analyzed statistically. RESULTS: The osteoclast-like cells of each group were Trap positive cells and could form the bone absorption lacunas in vitro. The amounts of osteoclast-like cells were different statistically between the groups (P < 0.05) except between the groups of 1-day old and 12-day old (P > 0.05). Highly enriched osteoclast-like cells were harvested by the digestion of 0.25% trypsin and 0.02% EDTA. CONCLUSION: It's indicated that a large amount of highly enriched osteoclast-like cells could be obtained through the culture of bone marrow cells of 10-day and 12-day old SD rats with 1,25-(OH)2D3 and dexamethasone and the digestion of trypsin/EDTA.

Animals↗

[Exploring the observation methods of photosynthetic responses to light and carbon dioxide].

Through observing the responses of photosynthesis in leaves of broad bean grown under natural conditions to light and CO(2) using a portable photosynthetic analyzer LI-6400, the following findings were obtained. (1) Observing the response of photosynthesis to light using a leaf without being induced by light might lead to an artifact that photosynthesis was not saturated even under full sunlight. (2) The calculated saturating light intensity of photosynthesis by some empirical equations was much lower than actual value obtained by observing. (3) During observation of photosynthetic response to CO(2), each step of changing CO(2) concentration should be accompanied by a match step of the photosynthetic analyzer, otherwise, there will be substantial deviations in the results obtained. (4) Observing photosynthetic response to CO(2) at non-saturating light might lead to an underestimation of leaf photosynthetic capacity.

Carbon Dioxide↗

Inclusion of unaffected sibs increases power in model-free linkage analysis of a behavioral trait.

Study design strategies are of critical importance in the search for genes underlying complex diseases. Two important design choices in planning gene mapping studies are the analytic strategy to be used, which will have an impact on the type of data to be collected, and the choice of genetic markers. In the present paper, we used the simulated behavioral trait data provided in the Genetic Analysis Workshop 14 to: 1) investigate the usefulness of incorporating unaffected sibs in model-free linkage analysis and, 2) compare linkage results of genome scans using a 7-cM microsatellite map with a 3-cM single nucleotide polymorphisms map. To achieve these aims, we used the maximum-likelihood-binomial method with two different coding approaches. We defined the unaffected sibs as those totally free of phenotypes correlated to the disease. Without prior knowledge of the answers, we were able to correctly localize 2 out of 5 loci (LOD > 3) in a sample of 200 families that included the unaffected sibs but only one locus when based on an affected-only strategy, using either microsatellite or SNPs genome scan. LOD scores were considerably higher using the analytic strategy which incorporated the unaffected sibs. In conclusion, including unaffected sibs in model-free linkage analysis of complex binary traits is helpful, at least when complete parental data are available, whereas there are no striking advantages in using single nucleotide polymorphisms over microsatellite map at marker densities used in the current study.

Behavior↗