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Yi Li

Publications and source records attributed to Yi Li.

At least 37 records · Page 2Linked to original sources
PubMed2007

4D-fingerprint categorical QSAR models for skin sensitization based on the classification of local lymph node assay measures.

Currently, the only validated methods to identify skin sensitization effects are in vivo models, such as the local lymph node assay (LLNA) and guinea pig studies. There is a tremendous need, in particular due to novel legislation, to develop animal alternatives, for eaxample, quantitative structure-activity relationship (QSAR) models. Here, QSAR models for skin sensitization using LLNA data have been constructed. The descriptors used to generate these models are derived from the 4D-molecular similarity paradigm and are referred to as universal 4D-fingerprints. A training set of 132 structurally diverse compounds and a test set of 15 structurally diverse compounds were used in this study. The statistical methodologies used to build the models are logistic regression (LR) and partial least-square coupled logistic regression (PLS-LR), which prove to be effective tools for studying skin sensitization measures expressed in the two categorical terms of sensitizer and non-sensitizer. QSAR models with low values of the Hosmer-Lemeshow goodness-of-fit statistic, X(2)HL, are significant and predictive. For the training set, the cross-validated prediction accuracy of the logistic regression models ranges from 77.3% to 78.0%, whereas that of the PLS-logistic regression models ranges from 87.1% to 89.4%. For the test set, the prediction accuracy of logistic regression models ranges from 80.0% to 86.7%, whereas that of the PLS-logistic regression models ranges from 73.3% to 80.0%. The QSAR models are made up of 4D-fingerprints related to aromatic atoms, hydrogen bond acceptors, and negatively partially charged atoms.

Animals↗
PubMed2007

Maize (Zea mays) genetic transformation by co-cultivating germinating seeds with Agrobacterium tumefaciens.

A novel plant genetic transformation method for maize (Zea mays) is reported. Using a scalpel, germinating seeds were wounded in the meristem and co-cultivated with an Agrobacterium tumefaciens strain harbouring a Ti plasmid. Seedlings produced from the treatment were screened by hygromycin selection. Fertile transgenic T(0) and T(1) plants were obtained. PCR amplification, PCR-Southern and Southern-blot analysis showed that the foreign gene had been introduced into the inbreds of maize. About 29% of T(0) seedlings examined were found to be transgenic, although the overall transformation was only 0.6% when total treated seeds were taken into account. The method circumvented tedious and prolonged tissue-culture steps, is simple and can be readily integrated into conventional plant breeding programs.

Agrobacterium tumefaciens↗
PubMed2006

Effect of ATM, CHEK2 and ERBB2 TAGSNPs and haplotypes on endometrial cancer risk.

Family history of endometrial cancer increases the risk of developing the disease, but it is still largely unknown which germ-line genetic factors are involved in the aetiology of endometrial cancer. In a Swedish population-based case-control study including 705 cases and 1565 controls, we examined common variation in the ATM, CHEK2 and ERBB2 genes in relation to endometrial cancer risk overall, restricted to tumours of certain characteristics or stratified by various endometrial cancer risk factors. We genotyped a large number of single-nucleotide polymorphisms (SNPs) in the genes and selected seven haplotype-tagging SNPs (tagSNPs) in ATM, six tagSNPs in CHEK2 and seven tagSNPs in ERBB2 that could predict common variants and haplotypes (frequency > or =0.03) in each gene with R(2) > or = 0.8. We included the tagSNPs or their haplotypes as explanatory variables in unconditional logistic regression models adjusted for age. Our results indicated an increased risk of developing endometroid endometrial cancer for homozygous carriers of the rare allele (AA) of a tagSNP (rs4987886) in CHEK2 (P = 0.005) when contrasted with GG carriers. We also found a decreased endometrial cancer risk among non-smoking carriers of a haplotype in ATM (P = 0.0007) and among carriers of a haplotype in CHEK2, who had experienced menopause below 49 years of age (P = 0.0009) compared with non-carriers of these haplotypes. We found no effect of genetic variation in ERBB2 on endometrial cancer risk. In conclusion, it is possible that common variants in the ATM and CHEK2 genes, in interaction with oestrogen-related exposures, are involved in endometrial cancer aetiology.

Age Factors↗
PubMed2006

Interaction of rice dwarf virus outer capsid P8 protein with rice glycolate oxidase mediates relocalization of P8.

Yeast two-hybrid and coimmunoprecipitation assays indicated that P8, an outer capsid protein of Rice dwarf phytoreovirus (RDV), interacts with rice glycolate oxidase (GOX), a typical enzyme of peroxisomes. Confocal immunofluorescence microscopy revealed that P8 was colocalized with GOX in peroxisomes. Time course analysis demonstrated that the localization of P8 in Spodoptera frugiperda cells changed from diffuse to discrete, punctuate inclusions during expression from 24 to 48 h post inoculation. Coexpression of GOX with P8 may target P8 into peroxisomes, which serve as replication sites for a number of viruses. Therefore, we conclude that the interaction of P8 with the GOX of host cells leads to translocation of P8 into peroxisomes and we further propose that the interaction between P8 and GOX may play important roles in RDV targeting into the replication site of host cells. Our findings have broad significance in studying the mechanisms whereby viruses target appropriate replication sites and begin their replication.

Alcohol Oxidoreductases↗
PubMed2006

Can ageing-related degenerative diseases be ameliorated through administration of vitamin C at pharmacological levels?

Man, with other primates, lost the ability to synthesize vitamin C through an inactivating mutation of the gene encoding gulonolactone oxidase (GULO) millions of years ago. Though the consequences of this prehistoric loss must have been favorable (and thus selected for) at the population level, the inability to produce vitamin C may have serious health implications for modern humans, especially for those conditions in which antioxidants (like vitamin C) have been implicated as potential therapeutic agents. Two general types of recent findings regarding vitamin C have made re-evaluation of this important nutrient imperative. First, vitamin C is now known to be involved in several novel physiological phenomena including stem cell differentiation and respiratory development, which likely require pharmacological levels of vitamin C. Secondly, the growing recognition that many ageing-related diseases, including heart disease, neural degeneration and cancer, may have a contributing oxidative damage factor that might be reduced by dietary antioxidants such as vitamin C. In this paper, we hypothesize that high serum-level vitamin C provides important, broad-ranging therapeutic benefits in treating ageing-related degenerative diseases. This hypothesis can be readily tested using traditional and newly-developed genetically-engineered animal models.

Aging↗
PubMed2006

Overexpression of an Arabidopsis magnesium transport gene, AtMGT1, in Nicotiana benthamiana confers Al tolerance.

Aluminium (Al) toxicity is the most important limiting factor for crop production in acid soil environments worldwide. In some plant species, application of magnesium (Mg(2+)) can alleviate Al toxicity. However, it remains unknown whether overexpression of magnesium transport proteins can improve Al tolerance. Here, the role of AtMGT1, a member of the Arabidopsis magnesium transport family involved in Mg(2+) transport, played in Al tolerance in higher plants was investigated. Expression of 35S::AtMGT1 led to various phenotypic alterations in Nicotiana benthamiana plants. Transgenic plants harbouring 35S::AtMGT1 exhibited tolerance to Mg(2+) deficiency. Element assay showed that the contents of Mg, Mn, and Fe in 35S::AtMGT1 plants increased compared with wild-type plants. Root growth experiment revealed that 100 microM AlCl(3) caused a reduction in root elongation by 47% in transgenic lines, whereas root growth in wild-type plants was inhibited completely. Upon Al treatment, representative transgenic lines also showed a much lower callose deposition, an indicator of increased Al tolerance, than wild-type plants. Taken together, the results have demonstrated that overexpression of ATMGT1 encoding a magnesium transport protein can improve tolerance to Al in higher plants.

Aluminum↗
PubMed2006

Introduction of oncogenes into mammary glands in vivo with an avian retroviral vector initiates and promotes carcinogenesis in mouse models.

We have adapted the avian leukosis virus RCAS (replication-competent avian sarcoma-leukosis virus LTR splice acceptor)-mediated somatic gene transfer technique to introduce oncogenes into mammary cells in mice transgenic for the avian subgroup A receptor gene, tva, under control of the mouse mammary tumor virus (MMTV) promoter. Intraductal instillation of an RCAS vector carrying the polyoma middle T antigen (PyMT) gene (RCAS-PyMT) induced multiple, oligoclonal tumors within 3 weeks in infected mammary glands of MMTV-tva transgenic mice. The rapid appearance of these tumors from a relatively small pool of infected cells (estimated to be approximately 2 x 10(3) cells per gland by infection with RCAS carrying a GFP gene; RCAS-GFP) was accompanied by a high fraction of cells positive for Ki67, Cyclin D1, and c-Myc, implying strong proliferation competence. Furthermore, the tumors displayed greater cellular heterogeneity than did tumors arising in MMTV-PyMT mice, suggesting that RCAS-PyMT transforms a relatively immature cell type. Infection of mice transgenic for both MMTV-Wnt-1 and MMTV-tva with RCAS virus carrying an activated Neu oncogene dramatically enhanced tumor formation over what is observed in uninfected bitransgenic animals. We conclude that infection of mammary glands with retrovirus vectors is an efficient means to screen candidate oncogenes for their capacity to initiate or promote mammary carcinogenesis in the mouse.

Animals↗
PubMed2006

A pivotal role for endogenous TGF-beta-activated kinase-1 in the LKB1/AMP-activated protein kinase energy-sensor pathway.

TGF-beta-activated kinase-1 (TAK1), also known as MAPKK kinase-7 (MAP3K7), is a candidate effector of multiple circuits in cardiac biology and disease. Here, we show that inhibition of TAK1 in mice by a cardiac-specific dominant-negative mutation evokes electrophysiological and biochemical properties reminiscent of human Wolff-Parkinson-White syndrome, arising from mutations in AMP-activated protein kinase (AMPK), most notably, accelerated atrioventricular conduction and impaired AMPK activation. To test conclusively the biochemical connection from TAK1 to AMPK suggested by this phenotype, we disrupted TAK1 in mouse embryos and embryonic fibroblasts by Cre-mediated recombination. In TAK1-null embryos, the activating phosphorylation of AMPK at T172 was blocked, accompanied by defective AMPK activity. However, loss of endogenous TAK1 causes midgestation lethality, with defective yolk sac and intraembryonic vasculature. To preclude confounding lethal defects, we acutely ablated floxed TAK1 in culture by viral delivery of Cre. In culture, endogenous TAK1 was activated by oligomycin, the antidiabetic drug metformin, 5-aminoimidazole-4-carboxamide riboside (AICAR), and ischemia, well established triggers of AMPK activity. Loss of TAK1 in culture blocked T172 phosphorylation induced by all three agents, interfered with AMPK activation, impaired phosphorylation of the endogenous AMPK substrate acetyl CoA carboxylase, and also interfered with activation of the AMPK kinase LKB1. Thus, by disrupting the endogenous TAK1 locus, we prove a pivotal role for TAK1 in the LKB1/AMPK signaling axis, an essential governor of cell metabolism.

AMP-Activated Protein Kinases↗
PubMed2006

Gastric lavage in acute organophosphorus pesticide poisoning (GLAOP)--a randomised controlled trial of multiple vs. single gastric lavage in unselected acute organophosphorus pesticide poisoning.

BACKGROUND: Organophosphorus (OP) pesticide poisoning is the most common form of pesticide poisoning in many Asian countries. Guidelines in western countries for management of poisoning indicate that gastric lavage should be performed only if two criteria are met: within one hour of poison ingestion and substantial ingested amount. But the evidence on which these guidelines are based is from medicine overdoses in developed countries and may be irrelevant to OP poisoning in Asia. Chinese clinical experience suggests that OP remains in the stomach for several hours or even days after ingestion. Thus, there may be reasons for doing single or multiple gastric lavages for OP poisoning. There have been no randomised controlled trials (RCTs) to assess this practice of multiple lavages. Since it is currently standard therapy in China, we cannot perform a RCT of no lavage vs. a single lavage vs. multiple lavages. We will compare a single gastric lavage with three gastric lavages as the first stage to assess the role of gastric lavage in OP poisoning. METHODS/DESIGN: We have designed an RCT assessing the effectiveness of multiple gastric lavages in adult OP self-poisoning patients admitted to three Chinese hospitals within 12 hrs of ingestion. Patients will be randomised to standard treatment plus either a single gastric lavage on admission or three gastric lavages at four hour intervals. The primary outcome is in-hospital mortality. Analysis will be on an intention-to-treat basis. On the basis of the historical incidence of OP at the study sites, we expect to enroll 908 patients over three years. This projected sample size provides sufficient power to evaluate the death rate; and a variety of other exposure and outcome variables, including particular OPs and ingestion time. Changes of OP level will be analyzed in order to provide some toxic kinetic data. DISCUSSION: the GLAOP study is a novel, prospective cohort study that will explore to the toxic kinetics of OP and effects of gastric lavage on it. Given the poor information about the impact of gastric lavage on clinical outcomes for OP patients, this study can provide important information to inform clinical practice.

Journal Article↗
PubMed2006

Activation of cyclin-dependent kinase 5 (Cdk5) in primary sensory and dorsal horn neurons by peripheral inflammation contributes to heat hyperalgesia.

Cyclin-dependent kinase 5 (Cdk5) is a unique member of the CDK family. It is predominantly expressed in postmitotic neurons and has been implicated in neuronal plasticity. The present study showed that Cdk5 and p35 were expressed in primary sensory and dorsal horn neurons, while p25, an N-terminal truncated derivative of p35, could only be detected in the dorsal horn neurons. Importantly, in the case of control rats, the p35 protein level was much higher in small- and medium-diameter DRG neurons than it was in large neurons. Following CFA injection, Cdk5 activity was upregulated in both primary sensory and dorsal horn neurons. Cdk5 activation in DRG neurons required p35, whereas p25 was required in the dorsal horn. Intrathecal pretreatment with Roscovitine, a specific inhibitor of Cdk5 activity, and intrathecal delivery of the DN-Cdk5(N144) gene both alleviated CFA-induced heat hyperalgesia but not mechanical allodynia. In contrast, overexpression of Cdk5, p35 or p25 in primary sensory and dorsal horn neurons significantly enhanced heat hyperalgesia. We conclude that Cdk5/p35 and Cdk5/p25 complexes in primary sensory and dorsal horn neurons may potentially be involved in nociceptive transmission after inflammation and may be employed in synaptic plasticity underlying pain hypersensitization.

Animals↗
PubMed2006

The Wnt signaling receptor Lrp5 is required for mammary ductal stem cell activity and Wnt1-induced tumorigenesis.

Canonical Wnt signaling has emerged as a critical regulatory pathway for stem cells. The association between ectopic activation of Wnt signaling and many different types of human cancer suggests that Wnt ligands can initiate tumor formation through altered regulation of stem cell populations. Here we have shown that mice deficient for the Wnt co-receptor Lrp5 are resistant to Wnt1-induced mammary tumors, which have been shown to be derived from the mammary stem/progenitor cell population. These mice exhibit a profound delay in tumorigenesis that is associated with reduced Wnt1-induced accumulation of mammary progenitor cells. In addition to the tumor resistance phenotype, loss of Lrp5 delays normal mammary development. The ductal trees of 5-week-old Lrp5-/- females have fewer terminal end buds, which are structures critical for juvenile ductal extension presumed to be rich in stem/progenitor cells. Consequently, the mature ductal tree is hypomorphic and does not completely fill the fat pad. Furthermore, Lrp5-/- ductal cells from mature females exhibit little to no stem cell activity in limiting dilution transplants. Finally, we have shown that Lrp5-/- embryos exhibit substantially impaired canonical Wnt signaling in the primitive stem cell compartment of the mammary placodes. These findings suggest that Lrp5-mediated canonical signaling is required for mammary ductal stem cell activity and for tumor development in response to oncogenic Wnt effectors.

Animals↗
PubMed2006

Subgrid-scale modeling of helicity and energy dissipation in helical turbulence.

The subgrid-scale (SGS) modeling of helical, isotropic turbulence in large eddy simulation is investigated by quantifying rates of helicity and energy cascade. Assuming Kolmogorov spectra, the Smagorinsky model with its traditional coefficient is shown to underestimate the helicity dissipation rate by about 40%. Several two-term helical models are proposed with the model coefficients calculated from simultaneous energy and helicity dissipation balance. The helical models are also extended to include dynamic determination of their coefficients. The models are tested a priori in isotropic steady helical turbulence. Together with the dynamic Smagorinsky model and the dynamic mixed model, they are also tested a posteriori in both decaying and steady isotropic helical turbulence by comparing results to direct numerical simulations (DNS). The a priori tests confirm that the Smagorinsky model underestimates SGS helicity dissipation, although quantitative differences with the predictions are observed due to the finite Reynolds number of the DNS. Also, in a posteriori tests improvement can be achieved for the helicity decay rate with the proposed models, compared with the Smagorinsky model. Overall, however, the effect of the new helical terms added to obtain the correct rate of global helicity dissipation is found to be quite small. Within the small differences, the various versions of the dynamic model provide the results closest to the DNS. The dynamic model's good performance in capturing mean kinetic energy dissipation at the finite Reynolds number of the simulations appears to be the most important aspect in accounting also for accurate prediction of the helicity dissipation.

Journal Article↗
PubMed2006

Bone marrow stromal cells reduce axonal loss in experimental autoimmune encephalomyelitis mice.

We investigated the ability of human bone marrow stromal cell (hBMSC) treatment to reduce axonal loss in experimental autoimmune encephalomyelitis (EAE) mice. EAE was induced in SJL/J mice by injection with proteolipid protein (PLP). Mice were injected intravenously with hBMSCs or PBS on the day of clinical onset, and neurological function was measured daily (score 0-5) until 45 weeks after onset. Mice were sacrificed at week 1, 10, 20, 34, and 45 after clinical onset. Bielshowsky silver was used to identify axons. Immunohistochemistry was performed to measure the expression of nerve growth factor (NGF) and MAB1281, a marker of hBMSCs. hBMSC treatment significantly reduced the mortality, the disease severity, and the number of relapses in EAE mice compared with PBS treatment. Axonal density and NGF(+) cells in the EAE brain were significantly increased in the hBMSC group compared with the PBS group at 1, 10, 20, 34, and 45 weeks. Disease severity was significantly correlated with decreased axonal density and decreased NGF, and increased axonal density was significantly correlated with reduced loss of NGF expression after hBMSC treatment. Most of the NGF(+) cells are brain parenchymal cells. Under 5% of MAB1281(+) cells colocalized with NG2(+), a marker of oligodendrocyte progenitor cells. Nearly 10% of MAB1281(+) cells colocalized with GFAP, a marker of astrocytes, and MAP-2, a marker of neurons. Our findings indicate that hBMSCs improve functional recovery and may provide a potential therapy aimed at axonal protection in EAE mice, in which NGF may play a vital role.

Animals↗
PubMed2006

Ameboid cell motility: a model and inverse problem, with an application to live cell imaging data.

In this article a mathematical model for ameboid cell movement is developed using a spring-dashpot system with Newtonian dynamics. The model is based on the facts that the cytoskeleton plays a primary role for cell motility and that the cytoplasm is viscoelastic. Based on the model, the inverse problem can be posed: if a structure like a spring-dashpot system is embedded into the living cell, what kind of characteristic properties must the structure have in order to reproduce a given movement of the cell? This inverse problem is the primary topic of this paper. On one side the model mimics some features of the movement, and on the other side, the solution to the inverse problem provides model parameters that give some insight, principally into the mechanical aspect, but also, through qualitative reasoning, into chemical and biophysical aspects of the cell. Moreover, this analysis can be done locally or globally and in different media by using the simplest possible information: positions of the cell and nuclear membranes. It is shown that the model and solution to the inverse problem for simulated data sets are highly accurate. An application to a set of live cell imaging data obtained from random movements of a human brain tumor cell (U87-MG human glioblastoma cell line) then provides an example of the efficiency of the model, through the solution of its inverse problem, as a way of understanding experimental data.

Cell Membrane↗
PubMed2006

No accelerated evolution of 3'UTR region in human for brain-expressed genes.

The difference in cognitive skills between humans and nonhuman primates is one of the major characters that define our own species. It was previously hypothesized that this divergence might be attributable to genetic differences at gene expression level, and the cis-regulating elements of gene 3'UTRs might play important roles in the post-transcriptional regulation of gene expression. In this study, we constructed a cDNA library from the prefrontal cortex of rhesus monkey and generated a total of 754 high-quality ESTs. Using rhesus macaque as outgroup, we calculated the evolutionary rates of the 3'UTRs of 52 brain-expressed genes in humans and chimpanzees in order to dissect the role of natural selection during primate brain evolution. Comparison of 52 orthologous gene sequences of human and chimpanzee indicated that the mean substitution rates at nonsynonymous sites (K(a)), synonymous sites (K(s)) and 3'UTRs (K(3u)) are 0.0024, 0.0116 and 0.0117, respectively. Relative rate tests and acceleration index tests demonstrated that only a few genes had significant rate divergence between human and chimpanzee. The 3'UTRs of the brain-expressed genes in primates has a similar evolutionary rate with the synonymous sites of the gene coding region, indicating a neutral evolution of the 3'UTR sequences in human.

3' Untranslated Regions↗
PubMed2006

Percutaneous coronary intervention for chronic total occlusion in 1263 patients: a single-center report.

BACKGROUND: Coronary chronic total occlusion (CTO) remains one of the most challenging lesion subsets in interventional cardiology, even with the development of medical device and operator expertise. This study was conducted to examine the relationship between lesion characteristics and procedural success and the incidence of in-hospital major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI) for CTO. METHODS: Clinical and coronary angiographic data of 1263 patients with CTO who underwent PCI between June 1995 and December 2005 in Shenyang General Hospital of PLA were retrospectively analyzed. RESULTS: There were 1625 CTO lesions located in 1596 vessels with a mean occlusion time of 48.9 months. A total of 1647 coronary stents were implanted to the target lesions. The overall patient and lesion success rates were 90.8% (1147/1263) and 88.9% (1445/1625), respectively. The success rate of PCI was declined with long duration of occlusion, abrupt missing stump, bridging collaterals > or = 15 mm in occluded length, moderate to severe calcification or tortuosity and ostial or distal location of CTO lesions (P < 0.05). Procedural failure occurred in 116 patients, caused by impossibility of guide-wire (81.0%) or balloon (19.0%) to pass through the occlusion. There was no death during procedure, but 2 patients suffered from acute stent thrombosis and other 9 patients had acute or late pericardial perforation. Those complications were all successfully treated. After procedure, 3 patients died, 4 experienced urgent target vessel revascularization because of subacute stent thrombosis and 1 underwent coronary bypass graft surgery due to coronary fistula during in-hospital period. The overall in-hospital MACE rate was 0.6% (8/1263). Drug-eluting stents were used in 198 patients without in-hospital MACE. CONCLUSIONS: In an experienced heart center, it is possible to obtain a relatively high success rate of PCI and favorable clinical outcomes for patients with coronary CTO lesions.

Adult↗
PubMed2006

Arabidopsis ABA INSENSITIVE4 regulates lipid mobilization in the embryo and reveals repression of seed germination by the endosperm.

Regulation of seed germination requires coordinate action by the embryo and surrounding endosperm. We used Arabidopsis thaliana to establish the relative roles of embryo and endosperm in the control of seed germination and seedling establishment. We previously showed that endospermic oil reserves are used postgerminatively via gluconeogenesis to fuel seedling establishment and that lipid breakdown is repressed by abscisic acid (ABA) in embryo but not endosperm tissues. Here, we use RNA amplification to describe the transcriptome of the endosperm and compare the hormone responses of endosperm and embryo tissues. We show that the endosperm responds to both ABA and gibberellin but that ABA in particular regulates nuclear but not plastid-encoded photosynthetic gene expression in the embryo. We also show that ABA INSENSITIVE4 (ABI4) expression is confined to the embryo, accounts for the major differences in embryo response to ABA, and defines a role for ABI4 as a repressor of lipid breakdown. Furthermore, ABI5 expression in the endosperm defines a second region of altered ABA signaling in the micropylar endosperm cap. Finally, embryo and endosperm ABA signaling mutants demonstrate the spatial specificity of ABA action in seed germination. We conclude that the single cell endosperm layer plays an active role in the regulation of seed germination in Arabidopsis.

Abscisic Acid↗