PubMed Health⌕ Search

Biomedical subjects

Ming Ouyang

Publications and source records attributed to Ming Ouyang.

14 recordsLinked to original sources
PubMed2005

DNA microarray data imputation and significance analysis of differential expression.

MOTIVATION: Significance analysis of differential expression in DNA microarray data is an important task. Much of the current research is focused on developing improved tests and software tools. The task is difficult not only owing to the high dimensionality of the data (number of genes), but also because of the often non-negligible presence of missing values. There is thus a great need to reliably impute these missing values prior to the statistical analyses. Many imputation methods have been developed for DNA microarray data, but their impact on statistical analyses has not been well studied. In this work we examine how missing values and their imputation affect significance analysis of differential expression. RESULTS: We develop a new imputation method (LinCmb) that is superior to the widely used methods in terms of normalized root mean squared error. Its estimates are the convex combinations of the estimates of existing methods. We find that LinCmb adapts to the structure of the data: If the data are heterogeneous or if there are few missing values, LinCmb puts more weight on local imputation methods; if the data are homogeneous or if there are many missing values, LinCmb puts more weight on global imputation methods. Thus, LinCmb is a useful tool to understand the merits of different imputation methods. We also demonstrate that missing values affect significance analysis. Two datasets, different amounts of missing values, different imputation methods, the standard t-test and the regularized t-test and ANOVA are employed in the simulations. We conclude that good imputation alleviates the impact of missing values and should be an integral part of microarray data analysis. The most competitive methods are LinCmb, GMC and BPCA. Popular imputation schemes such as SVD, row mean, and KNN all exhibit high variance and poor performance. The regularized t-test is less affected by missing values than the standard t-test. AVAILABILITY: Matlab code is available on request from the authors.

Algorithms↗
PubMed2005

A requirement for memory retrieval during and after long-term extinction learning.

Current learning theories are based on the idea that learning is driven by the difference between expectations and experience (the delta rule). In extinction, one learns that certain expectations no longer apply. Here, we test the potential validity of the delta rule by manipulating memory retrieval (and thus expectations) during extinction learning. Adrenergic signaling is critical for the time-limited retrieval (but not acquisition or consolidation) of contextual fear. Using genetic and pharmacologic approaches to manipulate adrenergic signaling, we find that long-term extinction requires memory retrieval but not conditioned responding. Identical manipulations of the adrenergic system that do not affect memory retrieval do not alter extinction. The results provide substantial support for the delta rule of learning theory. In addition, the timing over which extinction is sensitive to adrenergic manipulation suggests a model whereby memory retrieval occurs during, and several hours after, extinction learning to consolidate long-term extinction memory.

Animals↗
PubMed2005

Effects of intermedin(1-53) on cardiac function and ischemia/reperfusion injury in isolated rat hearts.

Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene-related peptide (CT/CGRP) family identified from human and other vertebrate tissues. Preprointermedin (preproIMD) can generate a 47 amino acid mature peptide (IMD(1-47)) and a shorter 40 amino acid one (IMD(8-47)) by proteolytic cleavage. Amino acid sequence analysis showed that cleavage sites are located between two basic amino acids at Arg93-Arg94, resulting in the production of preproIMD(95-147), namely IMD(1-53). The present study was designed to observe the effects of IMD(1-53) on cardiac function in ischemia/reperfusion (I/R) injury in isolated rat hearts. Perfusion with high-dose IMD(1-53) gave higher left ventricular systolic pressure (LVSP) and maximal rate of increase and decrease of left ventricle pressure (+/-LVdP/dt(max)), and coronary perfusion flow (CPF) than those of controls. Cardiac I/R induced a marked inhibition of cardiac function and myocardial injury. Reperfusion with IMD(1-53) significantly ameliorated the inhibited cardiac function and bradycardia induced by I/R. Compared with the I/R-treatment alone, IMD(1-53) reperfusion augmented CPF, LVSP, and maximal rate of increase and decrease of left ventricle pressure (+/-LVdP/dt(max)) and decreased LVDP. In addition, reperfusion with IMD(1-53)markedly attenuated the leakage of lactate dehydrogenase and malondialdehyde content in myocardia compared with I/R alone. Reperfusion with IMD(1-53)increased the content of cyclic adenosine monophosphate in comparison with I/R alone. Interestingly, the above IMD(1-53) effects are similar to those of adrenomedullin. These results suggest that IMD(1-53), like adrenomedullin, has cardioprotective effects against myocardial I/R injury.

Animals↗
PubMed2005

Global analysis of Pub1p targets reveals a coordinate control of gene expression through modulation of binding and stability.

Regulation of mRNA turnover is an important cellular strategy for posttranscriptional control of gene expression, mediated by the interplay of cis-acting sequences and associated trans-acting factors. Pub1p, an ELAV-like yeast RNA-binding protein with homology to T-cell internal antigen 1 (TIA-1)/TIA-1-related protein (TIAR), is an important modulator of the decay of two known classes of mRNA. Our goal in this study was to determine the range of mRNAs whose stability is dependent on Pub1p, as well as to identify specific transcripts that directly bind to this protein. We have examined global mRNA turnover in isogenic PUB1 and pub1delta strains through gene expression analysis and demonstrate that 573 genes exhibit a significant reduction in half-life in a pub1delta strain. We also examine the binding specificity of Pub1p using affinity purification followed by microarray analysis to comprehensively distinguish between direct and indirect targets and find that Pub1p significantly binds to 368 cellular transcripts. Among the Pub1p-associated mRNAs, 53 transcripts encoding proteins involved in ribosomal biogenesis and cellular metabolism are selectively destabilized in the pub1delta strain. In contrast, genes involved in transporter activity demonstrate association with Pub1p but display no measurable changes in transcript stability. Characterization of two candidate genes, SEC53 and RPS16B, demonstrate that both Pub1p-dependent regulation of stability and Pub1p binding require 3' untranslated regions, which harbor distinct sequence motifs. These results suggest that Pub1p binds to discrete subsets of cellular transcripts and posttranscriptionally regulates their expression at multiple levels.

3' Untranslated Regions↗
PubMed2005

Molecular characterization of thyroid toxicity: anchoring gene expression profiles to biochemical and pathologic end points.

Organic iodides have been shown to induce thyroid hypertrophy and increase alterations in colloid in rats, although the mechanism involved in this toxicity is unclear. To evaluate the effect that free iodide has on thyroid toxicity, we exposed rats for 2 weeks by daily gavage to sodium iodide (NaI). To compare the effects of compounds with alternative mechanisms (increased thyroid hormone metabolism and decreased thyroid hormone synthesis, respectively), we also examined phenobarbital (PB) and propylthiouracil (PTU) as model thyroid toxicants. Follicular cell hypertrophy and pale-staining colloid were present in thyroid glands from PB-treated rats, and more severe hypertrophy/colloid changes along with diffuse hyperplasia were present in thyroid glands from PTU-treated rats. In PB- and PTU-treated rats, thyroid-stimulating hormone (TSH) levels were significantly elevated, and both thyroxine and triiodothyronine hormone levels were significantly decreased. PB induced hepatic uridine diphosphate-glucuronyltransferase (UDPGT) activity almost 2-fold, whereas PTU reduced hepatic 5 -deiodinase I (5 -DI) activity to < 10% of control in support of previous reports regarding the mechanism of action of each chemical. NaI also significantly altered liver weights and UDPGT activity but did not affect thyroid hormone levels or thyroid pathology. Thyroid gene expression analyses using Affymetrix U34A GeneChips, a regularized t-test, and Gene Map Annotator and Pathway Profiler demonstrated significant changes in rhodopsin-like G-protein-coupled receptor transcripts from all chemicals tested. NaI demonstrated dose-dependent changes in multiple oxidative stress-related genes, as also determined by principal component and linear regression analyses. Differential transcript profiles, possibly relevant to rodent follicular cell tumor outcomes, were observed in rats exposed to PB and PTU, including genes involved in Wnt signaling and ribosomal protein expression.

Animals↗
PubMed2004

Adrenergic signaling plays a critical role in the maintenance of waking and in the regulation of REM sleep.

Many experiments have suggested that the adrenergic system is important for arousal and the regulation of sleep/wake states. Electrophysiological studies have found strong correlations between the firing of adrenergic neurons and arousal state. Lesions of adrenergic neurons have been reported to cause changes in sleep/wake regulation, although findings have been variable and sometimes transient. To more specifically address the role of adrenergic signaling in sleep/wake regulation, we performed electroencephalographic and electromyographic recordings in mice with a targeted disruption of the gene for dopamine beta-hydroxylase, the enzyme that converts dopamine to norepinephrine. These mice are unable to synthesize the endogenous adrenergic ligands norepinephrine and epinephrine. The mutant mice sleep approximately 2 h more each day. The decrease in waking is due to a considerable decrease in the duration of waking bouts in spite of an increase in the number of waking bouts and transitions from sleep to waking. In contrast, the amount of rapid-eye-movement (REM) sleep is only half that in control mice due to a decrease in the number and duration of REM sleep bouts. Delta power is selectively increased in the mutant mice, and there is much less variation in non-REM sleep delta power over 24 h. After 6 h of total sleep deprivation during the first half of the light period, there is no rebound recovery of sleep time in the mutant mice. These results provide genetic evidence that adrenergic signaling acts to maintain waking and is important for the regulation of REM sleep and possibly sleep homeostasis.

Adrenergic alpha-Agonists↗
PubMed2004

Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors.

Mice unable to synthesize norepinephrine (NE) and epinephrine due to targeted disruption of the dopamine beta-hydroxylase gene, Dbh, were used to critically test roles for NE in mediating acute behavioral changes elicited by different classes of antidepressants. To this end, we used the tail suspension test, one of the most widely used paradigms for assessing antidepressant activity and depression-related behaviors in normal and genetically modified mice. Dbh(-/-) mice failed to respond to the behavioral effects of various antidepressants, including the NE reuptake inhibitors desipramine and reboxetine, the monoamine oxidase inhibitor pargyline, and the atypical antidepressant bupropion, even though they did not differ in baseline immobility from Dbh(+/-) mice, which have normal levels of NE. Surprisingly, the effects of the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline, and paroxetine were also absent or severely attenuated in the Dbh(-/-) mice. In contrast, citalopram (the most selective SSRI) was equally effective at reducing immobility in mice with and without NE. Restoration of NE by using L-threo-3,4-dihydroxyphenylserine reinstated the behavioral effects of both desipramine and paroxetine in Dbh(-/-) mice, thus demonstrating that the reduced sensitivity to antidepressants is related to NE function, as opposed to developmental abnormalities resulting from chronic NE deficiency. Microdialysis studies demonstrated that the ability of fluoxetine to increase hippocampal serotonin was blocked in Dbh(-/-) mice, whereas citalopram's effect was only partially attenuated. These data show that NE plays an important role in mediating acute behavioral and neurochemical actions of many antidepressants, including most SSRIs.

Animals↗
PubMed2004

A distinct role for norepinephrine in memory retrieval.

A role for norepinephrine in learning and memory has been elusive and controversial. A longstanding hypothesis states that the adrenergic nervous system mediates enhanced memory consolidation of emotional events. We tested this hypothesis in several learning tasks using mutant mice conditionally lacking norepinephrine and epinephrine, as well as control mice and rats treated with adrenergic receptor agonists and antagonists. We find that adrenergic signaling is critical for the retrieval of intermediate-term contextual and spatial memories, but is not necessary for the retrieval or consolidation of emotional memories in general. The role of norepinephrine in retrieval requires signaling through the beta(1)-adrenergic receptor in the hippocampus. The results demonstrate that mechanisms of memory retrieval can vary over time and can be different from those required for acquisition or consolidation. These findings may be relevant to symptoms in several neuropsychiatric disorders as well as the treatment of cardiac failure with beta blockers.

Adrenergic Agonists↗
PubMed2004

Gaussian mixture clustering and imputation of microarray data.

MOTIVATION: In microarray experiments, missing entries arise from blemishes on the chips. In large-scale studies, virtually every chip contains some missing entries and more than 90% of the genes are affected. Many analysis methods require a full set of data. Either those genes with missing entries are excluded, or the missing entries are filled with estimates prior to the analyses. This study compares methods of missing value estimation. RESULTS: Two evaluation metrics of imputation accuracy are employed. First, the root mean squared error measures the difference between the true values and the imputed values. Second, the number of mis-clustered genes measures the difference between clustering with true values and that with imputed values; it examines the bias introduced by imputation to clustering. The Gaussian mixture clustering with model averaging imputation is superior to all other imputation methods, according to both evaluation metrics, on both time-series (correlated) and non-time series (uncorrelated) data sets.

Algorithms↗
PubMed2004

Potency of catecholamines and other L-tyrosine derivatives at the cloned mouse adrenergic receptors.

The adrenergic system is a neuromodulatory system whose endogenous ligands are considered to be the catecholamines norepinephrine (NE) and epinephrine (E). Evidence suggests that the catecholamine dopamine (DA) may also activate adrenergic signaling. Further, tyramine (TA) and octopamine (OA) are other monoamines that can be produced in catecholaminergic cells when tyrosine hydroxylase activity is low or absent, as in some genetic mouse models of adrenergic function. Here, we systematically examine the ability of these L-tyrosine-derived monoamines to activate all 10 known isoforms of the cloned mouse adrenergic receptors expressed in Chinese hamster ovary cells. In comparison to NE or E, DA is nearly as efficacious in this system but is from 1 to 4 orders of magnitude less potent. In comparison to DA, OA has roughly equivalent potency but is usually only a partial agonist. TA is either very weak or lacks agonism. Of note, all three mouse alpha(1) receptors increase cAMP, in contrast to results reported for human alpha(1d) receptors. In addition, a 12-amino acid hemagglutinin epitope tag added to the N-terminus of alpha(2) receptors selectively enhances the potency of NE approximately 10- to 100-fold, indicating that caution should be applied when interpreting physiological results from experiments using modified receptors.

Animals↗
PubMed2003

Five hundred sixty-five triples of chicken, human, and mouse candidate orthologs.

The Human Genome Project has provided abundant gene sequence information on human and important model organisms. The chicken is well positioned from an evolutionary standpoint to serve as a link between higher and lower organisms, particularly mammals, and amphibia and fish. In this study we used stringent criteria to select 565 triples of chicken, human, and mouse candidate orthologs. We analyze the sequences with respect to nucleotide and amino acid similarities. This analysis also allows measurement of evolutionary distances of different proteins. We found that chicken-human and chicken-mouse sequence identities are highly correlated; similarly for chicken-human and chicken-mouse evolutionary distances. With chicken as the out-group, we found that mouse has a higher substitution rate than human, supporting the generation-time effect hypothesis. We also described the transversion bias, which is the preference for some transversions than others in nucleotide substitutions. We demonstrated that there are statistically significant properties in the differences of orthologous sequences. The differential patterns, in combination with sequence similarity analysis, may lead to the identification of genes that are very divergent from the mammalian orthologs.

Animals↗
PubMed2003

[Etiological diagnosis of chronic cough with unknown causes].

OBJECTIVE: To explore the spectrum and frequency of causes for chronic cough in Chinese patients. METHODS: 86 patients with chronic cough were enrolled in the study. The diagnostic procedure was based on the anatomical protocol for diagnosing chronic cough designed by Irwin, and additional cytological assay was performed for sputum induced by hypertonic saline aerosol inhalation. The efficacy of therapy specific to the diagnosis was evaluated. RESULTS: Definite diagnosis was made in 77 (89.5%) out of the 86 patients with chronic cough. The most common causes included cough variant asthma (CVA) (24/86, 27.9%), postnasal drip syndrome (PNDs) (22/86, 25.6%), eosinophilic bronchitis (EB) (13/86, 15.1%), and gastroesophageal reflux (GER) (12/86, 14.0%). After active management based on the diagnosis, cough improved in 72 patients (93.5%). CONCLUSIONS: In addition to CVA, PNDs and GER, eosinophilic bronchitis is also an important cause of chronic cough. A positive response to the specific therapy is essential to a definite diagnosis.

Adolescent↗
PubMed2002

Synthesis of vesicles on polymer template.

Reactive single-tail cationic surfactants self-assemble on the anionic block copolymer templates. These systems spontaneously arrange in small vesicles of nanoscale size. The vesicles are further stabilized by dimerization of the assembled surfactant monomers forming double-tail surfactants bound to the block copolymer. The resulting systems are resistant to changes in environmental characteristics such as pH, ionic strength, and temperature variations. Hydrophilic macromolecules can be encapsulated in the internal aqueous volume of these vesicles. The simplicity of the preparation makes these systems promising as drug and gene delivery carriers.

Isothiuronium↗