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Biomedical subjects

Ping Ye

Publications and source records attributed to Ping Ye.

At least 19 recordsLinked to original sources
PubMed2007

Insulin-like growth factor type 1 receptor signaling in the cells of oligodendrocyte lineage is required for normal in vivo oligodendrocyte development and myelination.

Insulin-like growth factor-I (IGF-I) has been shown to be a potent agent in promoting the growth and differentiation of oligodendrocyte precursors, and in stimulating myelination during development and following injury. To definitively determine whether IGF-I acts directly on the cells of oligodendrocyte lineage, we generated lines of mice in which the type 1 IGF receptor gene (igf1r) was conditionally ablated either in Olig1 or proteolipid protein expressing cells (termed IGF1R(pre-oligo-ko) and IGF1R(oligo-ko) mice, respectively). Compared with wild type mice, IGF1R(pre-oligo-ko) mice had a decreased volume (by 35-55%) and cell number (by 54-70%) in the corpus callosum (CC) and anterior commissure at 2 and 6 weeks of age, respectively. IGF1R(oligo-ko) mice by 25 weeks of age also showed reductions, albeit less marked, in CC volume and cell number. Unlike astrocytes, the percentage of NG2(+) oligodendrocyte precursors was decreased by approximately 13% in 2-week-old IGF1R(pre-oligo-ko) mice, while the percentage of CC1(+) mature oligodendrocytes was decreased by approximately 24% in 6-week-old IGF1R(pre-oligo-ko) mice and approximately 25% in 25-week-old IGF1R(oligo-ko) mice. The reduction in these cells is apparently a result of decreased proliferation and increased apoptosis. These results indicate that IGF-I directly affects oligodendrocytes and myelination in vivo via IGF1R, and that IGF1R signaling in the cells of oligodendrocyte lineage is required for normal oligodendrocyte development and myelination. These data also provide a fundamental basis for developing strategies with the potential to target IGF-IGF1R signaling pathways in oligodendrocyte lineage cells for the treatment of demyelinating disorders.

Animals↗
PubMed2007

The alteration of plasminogen activator inhibitor-1 expression by linoleic acid and fenofibrate in HepG2 cells.

The present study investigated the influence of linoleic acid and fenofibrate on plasminogen activator inhibitor-1 (PAI-1) expression in HepG2 cells and the mechanism possibly involved. Using gene recombination techniques, chloromycetin acetyltransferase (CAT) reporter gene plasmids containing nuclear factor-kappaB response element deletion (del1-PAI-pCAT) or very-low-density lipoprotein/fatty acid response element deletion (del2-PAI-pCAT) in the PAI-1 promoter were constructed and transiently transfected into HepG2 cells, respectively. Linoleic acid and fenofibrate were added to induce the transfected cells. The PAI-1 expression in mRNA and protein level was significantly induced by linoleic acid, but suppressed by fenofibrate. In the HepG2 cells transfected with PAI-pCAT plasmid, the PAI-1 transcription activity was significantly induced by linoleic acid, but suppressed by fenofibrate. Under transfection with del1-PAI-pCAT, both linoleic acid and fenofibrate increased the PAI-1 transcriptional activity; whereas in those cells transfected with del2-PAI-pCAT, fenofibrate significantly reduced PAI-1 transcriptional activity but no change was found with linoleic acid stimulation. Peroxisome proliferator-activated receptor alpha may be one of transcription factors playing a role in the upregulation of PAI-1 gene expression by linoleic acid in HepG2 cells. The inhibition of the nuclear factor-kappaB signaling pathway may be involved in the downregulation of PAI-1 gene expression by fenofibrate.

Cell Line, Tumor↗
PubMed2006

Active retrotransposition by a synthetic L1 element in mice.

Long interspersed element type 1 (L1) retrotransposons are ubiquitous mammalian mobile elements and potential tools for in vivo mutagenesis; however, native L1 elements are relatively inactive in mice when introduced as transgenes. We have previously described a synthetic L1 element, ORFeus, containing two synonymously recoded ORFs relative to mouse L1. It is significantly more active for retrotransposition in cell culture than all native L1 elements tested. To study its activity in vivo, we developed a transgenic mouse model in which ORFeus expression was controlled by a constitutive heterologous promoter, and we established definitive evidence for ORFeus retrotransposition activity both in germ line and somatic tissues. Germ line retrotransposition frequencies resulting in 0.33 insertions per animal are seen among progeny of ORFeus donor element heterozygotes derived from a single founder, representing a >20-fold increase over native L1 elements. We observe somatic transposition events in 100% of the ORFeus donor-containing animals, and an average of 17 different insertions are easily recovered from each animal; modeling suggests that the number of somatic insertions per animal exceeds this number by perhaps several orders of magnitude. Nearly 200 insertions were precisely mapped, and their distribution in the mouse genome appears random relative to transcription units and guanine-cytosine content. The results suggest that ORFeus may be developed into useful tools for in vivo mutagenesis.

Animals↗
PubMed2006

Calculated tear oxygen tension under contact lenses offering resistance in series: piggyback and scleral lenses.

BACKGROUND: Models of oxygen delivery to the cornea with contact lens wear have considered the customary situation of one lens being worn on the cornea. However, two lenses, such as a rigid lens piggybacked on a soft lens, may be worn by patients with special ocular and visual needs. This paper extends existing single lens models to circumstances where two lenses offer resistance to oxygen in series. METHODS: Theoretical oxygen tensions are calculated for tear layers trapped beneath piggyback contact lens systems (and scleral lenses) and the anterior corneal surface with a simple single chamber corneal model using a personal computer software spreadsheet. RESULTS: Acceptable values are anticipated for contact lens materials of modern oxygen permeability values of approximately 60-100 Fatt Dk units under open eye conditions. CONCLUSIONS: The results of this spreadsheet model of oxygen supply to the anterior corneal surface offer a useful guide to clinicians concerned about providing their patients with physiologically acceptable piggyback lens systems.

Contact Lenses↗
PubMed2006

A DNA integrity network in the yeast Saccharomyces cerevisiae.

A network governing DNA integrity was identified in yeast by a global genetic analysis of synthetic fitness or lethality defect (SFL) interactions. Within this network, 16 functional modules or minipathways were defined based on patterns of global SFL interactions. Modules or genes involved in DNA replication, DNA-replication checkpoint (DRC) signaling, and oxidative stress response were identified as the major guardians against lethal spontaneous DNA damage, efficient repair of which requires the functions of the DNA-damage checkpoint signaling and multiple DNA-repair pathways. This genome-wide genetic interaction network also identified novel components (DIA2, NPT1, HST3, HST4, and the CSM1 module) that potentially contribute to mitotic DNA replication and genomic stability and revealed novel functions of well-studied genes (the CTF18 module) in DRC signaling. This network will guide more detailed characterization of mechanisms governing DNA integrity in yeast and other organisms.

Chromosomal Proteins, Non-Histone↗
PubMed2006

Insulin-like growth factor actions during development of neural stem cells and progenitors in the central nervous system.

Insulin-like growth factor-I (IGF-I) plays a key role in normal development. Recent studies show that IGF-I exerts a wide variety actions in the central nervous system during development as well as in adulthood. This report reviews recent developments on IGF-I actions and its mechanisms in the central nervous system, with a focus on its actions during the development of neural stem cells and progenitors. Available data strongly indicate that IGF-I shortens the length of the cell cycle in neuron progenitors during embryonic life and has an influence on the growth of all neural cell types. The phosphatidylinositol-3 kinase/Akt and mitogen-activated protein kinase pathways seem to be the predominant mediators of IGF-I-stimulated neural cell proliferation and survival. IGF-I actions, however, likely depend on cell type, developmental stage, and microenvironmental milieu.

Animals↗
PubMed2006

Phasing RNA polymerase II using intrinsically bound Zn atoms: an updated structural model.

Macromolecular assemblies as large as RNA polymerase II (Pol II) can be phased by a few intrinsically bound Zn atoms, by using MAD experiments as described here. A phasing effectiveness of 570 aa/Zn is attained for Pol II. The resulting experimental, unbiased electron density map is of such quality that it confirms the existing crystallographic model and further reveals structural regions not shown by model phases, thus updating the Pol II model at three sites. The mechanistically important fork loop-1 element is observed to be ordered in the absence of nucleic acids, suggesting additional insights into the mechanisms that maintain the stability of the transcription ternary complex and allow its release. Furthermore, a computational experiment with simulated MAD data sets demonstrates that 1 Zn site is able to provide adequate experimental phase information for as many as 1100 amino acids of polypeptide, under the conditions of the current synchrotron and detector technologies.

Binding Sites↗
PubMed2006

Role of duodenogastroesophageal reflux in the pathogenesis of esophageal mucosal injury and gastroesophageal reflux symptoms.

BACKGROUND AND AIM: Patients with gastroesophageal reflux disease (GERD) usually suffer from acid reflux and duodenogastroesophageal reflux (DGER) simultaneously. The question of whether DGER has an important effect on the development of GERD remains controversial. The aim of the present study was to investigate the role of DGER in the pathogenesis of GERD and its value for the diagnosis of nonerosive reflux disease (NERD). METHODS: GERD was initially diagnosed using the reflux disease questionnaire. For further diagnosis, results of the upper gastrointestinal endoscopy (excluding a diagnosis of Barrett's esophagus) were considered in conjunction with simultaneous 24 h esophageal pH and bilirubin monitoring. RESULTS: According to endoscopic findings, 95 patients (43 men, 50+/-10 years of age) were divided into two groups: the reflux esophagitis (RE) group (n=51) and the NERD group (n=44). Three DGER parameters, the percentage of time with absorbance greater than 0.14, the total number of reflux episodes and the number of bile reflux episodes lasting longer than 5 min, were evaluated in the study. For the RE group, the values of the DGER parameters (19.05%+/-23.44%, 30.56+/-34.04 and 5.90+/-6.37, respectively) were significantly higher than those of the NERD group (7.26%+/-11.08%, 15.68+/-20.92 and 2.59+/-3.57, respectively, P<0.05 for all) but no significant difference was found in acid reflux. Of NERD patients, 18.5% were diagnosed with simple DGER. The positive diagnosis rate of NERD could be significantly elevated from 65.9% to 84.1% (P<0.05), if bilirubin monitoring was employed in diagnosis. CONCLUSIONS: DGER may occur independently but plays an important role in the development of RE and GERD symptoms. Simultaneous 24 h esophageal pH and bilirubin monitoring is superior to simple pH monitoring in helping identify patients at risk for NERD.

Adult↗
PubMed2006

Effect of aging on the expression of peroxisome proliferator-activated receptor gamma and the possible relation to insulin resistance.

BACKGROUND: The morbidity of insulin resistance tends to increase with aging. However, studies on molecular mechanisms underlying insulin resistance in aging process is still in paucity. OBJECTIVE: The effect of aging on peroxisome proliferator-activated receptor gamma (PPARgamma) expression, and in addition, the possible association of PPARgamma expression with insulin resistance in aging process were investigated. METHODS: The minimal model technique (MMT) based on frequently sampled intravenous glucose tolerance test was adopted and SI and glucose effectiveness of young and aged rats were compared. RT-PCR and Western blot were used to determine the expression of PPARgamma at mRNA and protein level in adipose tissue and skeletal muscle, as well as in human colic omentum, respectively. RESULTS: MMT result implied existence of various degrees of insulin resistance in aged rats. The expression of PPARgamma at both mRNA and protein levels in adipose tissue of aged rats dramatically decreased; consequently, the expression of its target gene lipoprotein lipases mRNA also markedly decreased compared with those in young rats. Furthermore, the level of PPARgamma mRNA and glucose transporter-4 mRNA in skeletal muscle of aged rats attenuated significantly. The expression of PPARgamma mRNA in omental adipose tissue of old men was significantly decreased, accompanied by a tendency of higher insulin resistance index, compared with those of the young. CONCLUSION: Aging may be associated with diminished PPARgamma expression affecting insulin resistance in the aged individuals.

Adipose Tissue↗
PubMed2006

Atorvastatin attenuating down-regulation of peroxisome proliferator-activated receptor gamma in preventing cardiac hypertrophy of rats in vitro and in vivo.

PURPOSE: To investigate whether the role of atorvastatin in suppression of cardiac hypertrophy is potentially associated with the change of peroxisome proliferator-activated receptor gamma (PPARgamma) expression, and the anti-inflammatory effect in vitro and in vivo. METHOD: Cardiac hypertrophy was established by angiotensin II in neonatal cardiac myocytes in vitro and incomplete ligation of abdominal aorta of SD rats in vivo. PPARgamma and cytokines mRNA expression was evaluated by RT-PCR, and the rate of protein synthesis in cardiac myocytes by 3H-leucine incorporation. RESULTS: Atorvastatin attenuated downregulation of PPARgamma mRNA and inhibited brain natriuretic peptide (BNP), interleukin-1beta (IL-1beta) and matrix metalloproteinase 9 (MMP9) mRNA expression, as well as 3H-leucine incorporation in a dose-dependent manner in vitro. Furthermore, atorvastatin reduced the mRNA expression of BNP, IL-1beta and MMP9, and enhanced PPARgamma mRNA expression, and diminished the pressure overload-induced increase in the ratio of heart weight to body weight, left ventricular wall thickness and myocyte diameter of rats in vivo. CONCLUSION: Atorvastatin prevents cardiac hypertrophy of rats, probably associated with the modulation of PPARgamma and the inhibition of myocardial inflammation. Atorvastatin may play a role in prevention and treatment of cardiovascular diseases characterized by cardiac hypertrophy.

Animals↗
PubMed2006

[The beneficial effects of xuezhikang on top of extended-released nifedipine in hypertensive patients without severe hyperlipidemia].

OBJECTIVE: To investigate whether xuezhikang has additional beneficial effect on lipid peroxidation, myocardial fibrosis, inflammation and blood pressure control in hypertensive patients without sever hyperlipidemia treated with extended-released nifedipine. METHODS: This is a randomized, single-blind, placebo-controlled study, 100 patients with primary hypertension (HT) and normal or lightly elevated cholesterol level were randomized to receive placebo (n=49) or xuezhikang (1200 mg/d, n=51) for 24 weeks on top of extended-released nifedipine (20 mg, bid), 30 healthy volunteers served as controls. Plasma was obtained at baseline and 24 weeks after therapy. Lipids, C-reactive protein (CRP), malondialdehyde (MDA), superoxide dismutase photo-inhibition rate (SOD-PR) and type I collagen carboxypropeptide (PIP) were measured. RESULTS: Normal blood pressure (<140/90 mm Hg) was found in 49 out of 51 xuezhikang treated patients and in 40 out of 49 placebo treated patients (P<0.01) after 24 weeks therapy. Plasma CRP, MDA, SOD-PR and PIP were significantly higher in HT patients than those in normal controls. Plasma CRP, MDA, PIP and SOD-PR were significantly decreased in xuezhikang group while remained unchanged in placebo group after 24 weeks treatment. CONCLUSION: In patients with primary hypertension without severe hyperlipidemia treated with nifedipine, xuezhikang treatment exerts additional beneficial effects including better blood pressure control, endothelial function improvement, lipid oxidation loading attenuation and anti-inflammation.

Cholesterol, HDL↗
PubMed2006

[The effect of Xuezhikang on ventricular diastolic function in hypertension].

OBJECTIVE: To investigate whether statins have effect on diastolic function of both left and right ventricles in hypertensive patients. METHODS: This is a randomized, mono-blind, placebo-controlled study. 120 systemic hypertensive (HT) patients with normal or slightly elevated cholesterol were randomized to placebo or Xuezhikang (1200 mg/d) for 24 weeks. Extended-release nifedipine was administrated to the HT patients. 30 healthy volunteers served as controls. Plasma were obtained at baseline and 24 weeks after Xuezhikang therapy. Cholesterol and carboxy-terminal peptide of procollagen type I (PIP) were measured. Early diastolic velocity (Em) and late diastolic velocity (Am) were obtained from right atrioventricular ring and left atrioventricular ring with pulsed wave tissue Doppler imaging. RESULTS: The levels of plasma PIP were higher in HT patients. After 24 weeks, the levels of plasma LDL-C, TC and PIP were significantly lower in Xuezhikang group than those in placebo group; Systolic and diastolic pressure were decreased both in placebo group and Xuezhikang group meanwhile pulse pressure was decreased and Em/Am ratio at left atrioventricular ring was higher in Xuezhikang group as compared with those in placebo group. CONCLUSION: In systemic hypertensive patients, Xuezhikang exerts a beneficial effect on diastolic function of left ventricule via controlling blood pressure, lowering blood lipid and inhibiting myocardial fibrosis.

Aged↗
PubMed2005

Genetic Interaction Motif Finding by expectation maximization--a novel statistical model for inferring gene modules from synthetic lethality.

BACKGROUND: Synthetic lethality experiments identify pairs of genes with complementary function. More direct functional associations (for example greater probability of membership in a single protein complex) may be inferred between genes that share synthetic lethal interaction partners than genes that are directly synthetic lethal. Probabilistic algorithms that identify gene modules based on motif discovery are highly appropriate for the analysis of synthetic lethal genetic interaction data and have great potential in integrative analysis of heterogeneous datasets. RESULTS: We have developed Genetic Interaction Motif Finding (GIMF), an algorithm for unsupervised motif discovery from synthetic lethal interaction data. Interaction motifs are characterized by position weight matrices and optimized through expectation maximization. Given a seed gene, GIMF performs a nonlinear transform on the input genetic interaction data and automatically assigns genes to the motif or non-motif category. We demonstrate the capacity to extract known and novel pathways for Saccharomyces cerevisiae (budding yeast). Annotations suggested for several uncharacterized genes are supported by recent experimental evidence. GIMF is efficient in computation, requires no training and automatically down-weights promiscuous genes with high degrees. CONCLUSION: GIMF effectively identifies pathways from synthetic lethality data with several unique features. It is mostly suitable for building gene modules around seed genes. Optimal choice of one single model parameter allows construction of gene networks with different levels of confidence. The impact of hub genes the generic probabilistic framework of GIMF may be used to group other types of biological entities such as proteins based on stochastic motifs. Analysis of the strongest motifs discovered by the algorithm indicates that synthetic lethal interactions are depleted between genes within a motif, suggesting that synthetic lethality occurs between-pathway rather than within-pathway.

Algorithms↗
PubMed2005

Global synthetic-lethality analysis and yeast functional profiling.

The Saccharomyces genome-deletion project created >5900 'molecularly barcoded' yeast knockout mutants (YKO mutants). The YKO mutant collections have facilitated large-scale analyses of a multitude of mutant phenotypes. For example, both synthetic genetic array (SGA) and synthetic-lethality analysis by microarray (SLAM) methods have been used for synthetic-lethality screens. Global analysis of synthetic lethality promises to identify cellular pathways that 'buffer' each other biologically. The combination of global synthetic-lethality analysis, together with global protein-protein interaction analyses, mRNA expression profiling and functional profiling will, in principle, enable construction of a cellular 'wiring diagram' that will help frame a deeper understanding of human biology and disease.

Chromosome Mapping↗
PubMed2005

Gene function prediction from congruent synthetic lethal interactions in yeast.

We predicted gene function using synthetic lethal genetic interactions between null alleles in Saccharomyces cerevisiae. Phenotypic and protein interaction data indicate that synthetic lethal gene pairs function in parallel or compensating pathways. Congruent gene pairs, defined as sharing synthetic lethal partners, are in single pathway branches. We predicted benomyl sensitivity and nuclear migration defects using congruence; these phenotypes were uncorrelated with direct synthetic lethality. We also predicted YLL049W as a new member of the dynein-dynactin pathway and provided new supporting experimental evidence. We performed synthetic lethal screens of the parallel mitotic exit network (MEN) and Cdc14 early anaphase release pathways required for late cell cycle. Synthetic lethal interactions bridged genes in these pathways, and high congruence linked genes within each pathway. Synthetic lethal interactions between MEN and all components of the Sin3/Rpd3 histone deacetylase revealed a novel function for Sin3/Rpd3 in promoting mitotic exit in parallel to MEN. These in silico methods can predict phenotypes and gene functions and are applicable to genomic synthetic lethality screens in yeast and analogous RNA interference screens in metazoans.

Alleles↗
PubMed2005

Fcp1 directly recognizes the C-terminal domain (CTD) and interacts with a site on RNA polymerase II distinct from the CTD.

Fcp1 is an essential protein phosphatase that hydrolyzes phosphoserines within the C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II). Fcp1 plays a major role in the regulation of CTD phosphorylation and, hence, critically influences the function of Pol II throughout the transcription cycle. The basic understanding of Fcp1-CTD interaction has remained ambiguous because two different modes have been proposed: the "dockingsite" model versus the "distributive" mechanism. Here we demonstrate biochemically that Fcp1 recognizes and dephosphorylates the CTD directly, independent of the globular non-CTD part of the Pol II structure. We point out that the recognition of CTD by the phosphatase is based on random access and is not driven by Pol II conformation. Results from three different types of experiments reveal that the overall interaction between Fcp1 and Pol II is not stable but dynamic. In addition, we show that Fcp1 also interacts with a region on the polymerase distinct from the CTD. We emphasize that this non-CTD site is functionally distinct from the docking site invoked previously as essential for the CTD phosphatase activity of Fcp1. We speculate that Fcp1 interaction with the non-CTD site may mediate its stimulatory effect on transcription elongation reported previously.

Chromatography, Gel↗
PubMed2005

Commensurate distances and similar motifs in genetic congruence and protein interaction networks in yeast.

BACKGROUND: In a genetic interaction, the phenotype of a double mutant differs from the combined phenotypes of the underlying single mutants. When the single mutants have no growth defect, but the double mutant is lethal or exhibits slow growth, the interaction is termed synthetic lethality or synthetic fitness. These genetic interactions reveal gene redundancy and compensating pathways. Recently available large-scale data sets of genetic interactions and protein interactions in Saccharomyces cerevisiae provide a unique opportunity to elucidate the topological structure of biological pathways and how genes function in these pathways. RESULTS: We have defined congruent genes as pairs of genes with similar sets of genetic interaction partners and constructed a genetic congruence network by linking congruent genes. By comparing path lengths in three types of networks (genetic interaction, genetic congruence, and protein interaction), we discovered that high genetic congruence not only exhibits correlation with direct protein interaction linkage but also exhibits commensurate distance with the protein interaction network. However, consistent distances were not observed between genetic and protein interaction networks. We also demonstrated that congruence and protein networks are enriched with motifs that indicate network transitivity, while the genetic network has both transitive (triangle) and intransitive (square) types of motifs. These results suggest that robustness of yeast cells to gene deletions is due in part to two complementary pathways (square motif) or three complementary pathways, any two of which are required for viability (triangle motif). CONCLUSION: Genetic congruence is superior to genetic interaction in prediction of protein interactions and function associations. Genetically interacting pairs usually belong to parallel compensatory pathways, which can generate transitive motifs (any two of three pathways needed) or intransitive motifs (either of two pathways needed).

Protein Interaction Mapping↗