Biomedical subjects

Xiaohui Liu

Publications and source records attributed to Xiaohui Liu.

At least 19 recordsLinked to original sources

PubMed2026

The Znf711-Phf8 complex functions as a transcriptional rheostat essential for neutrophil development.

Neutrophil differentiation is governed by a precise transcriptional and epigenetic program. Here, we identify the zinc finger protein 711 (Znf711) and its partner, the histone demethylase PHD finger protein 8 (Phf8), as essential regulators of terminal granulopoiesis. Contrary to their established role as a transcriptional activator-co-activator pair, we found that the Znf711- Phf8 complex operates through a repressive mechanism. Znf711 promotes neutrophil maturation in a DNA-binding-independent manner by sequestering Phf8. Upon loss of Znf711, Phf8 is recruited by the growth factor independent 1 transcription repressor (Gfi1aa) to the promoter of the master regulator c/ebpα, where SUMOylated Phf8 acts as a corepressor to inhibit its transcription. Furthermore, we delineate a positive feedback loop wherein C/ebpα directly activates znf711 expression, ensuring a high level of c/ebpα at the onset of differentiation. Our findings define the Znf711-Phf8 complex as a critical transcriptional rheostat in neutrophil development.

Humans↗

PubMed2006

Transcriptional regulation of ethylene receptor and CTR genes involved in ethylene-induced flower opening in cut rose (Rosa hybrida) cv. Samantha.

In this work, the effect of ethylene on flower opening of cut rose (Rosa hybrida) cv. Samantha was studied. However, although ethylene hastened the process of flower opening, 1-MCP (1-methylcyclopropene), an ethylene action inhibitor, impeded it. Ethylene promoted ethylene production in petals, but 1-MCP did not inhibit this process. Of the four ethylene biosynthetic genes tested, Rh-ACS1 and Rh-ACS2 were undetectable; Rh-ACS3 and Rh-ACO1 expression was enhanced by ethylene slightly and greatly, respectively. However, their mRNA amounts were not inhibited by 1-MCP compared with controls. Expression of seven signalling component genes was also studied, including three ethylene receptors (Rh-ETR1, Rh-ETR3, and Rh-ETR5), two CTRs (Rh-CTR1 and Rh-CTR2), and two transcription factors (Rh-EIN3-1 and Rh-EIN3-2). Transcripts of Rh-ETR5, Rh-EIN3-1, and Rh-EIN3-2 were accumulated in a constitutive manner and had no or little response to ethylene or 1-MCP, while transcript levels of Rh-ETR1 and Rh-CTR1 were substantially elevated by ethylene, and those of Rh-ETR3 and Rh-CTR2 were greatly enhanced by ethylene; 1-MCP reduced all the four genes to levels much less than those in control flowers. These results show that ethylene triggers physiological responses related to flower opening in cut rose cv. Samantha, and that continued ethylene perception results in flower opening. Ethylene may regulate flower opening mainly through expression of two ethylene receptor genes (Rh-ETR1 and Rh-ETR3) and two CTR (Rh-CTR1 and Rh-CTR2) genes.

Cyclopropanes↗

PubMed2006

Exploiting the full power of temporal gene expression profiling through a new statistical test: application to the analysis of muscular dystrophy data.

BACKGROUND: The identification of biologically interesting genes in a temporal expression profiling dataset is challenging and complicated by high levels of experimental noise. Most statistical methods used in the literature do not fully exploit the temporal ordering in the dataset and are not suited to the case where temporal profiles are measured for a number of different biological conditions. We present a statistical test that makes explicit use of the temporal order in the data by fitting polynomial functions to the temporal profile of each gene and for each biological condition. A Hotelling T2-statistic is derived to detect the genes for which the parameters of these polynomials are significantly different from each other. RESULTS: We validate the temporal Hotelling T2-test on muscular gene expression data from four mouse strains which were profiled at different ages: dystrophin-, beta-sarcoglycan and gamma-sarcoglycan deficient mice, and wild-type mice. The first three are animal models for different muscular dystrophies. Extensive biological validation shows that the method is capable of finding genes with temporal profiles significantly different across the four strains, as well as identifying potential biomarkers for each form of the disease. The added value of the temporal test compared to an identical test which does not make use of temporal ordering is demonstrated via a simulation study, and through confirmation of the expression profiles from selected genes by quantitative PCR experiments. The proposed method maximises the detection of the biologically interesting genes, whilst minimising false detections. CONCLUSION: The temporal Hotelling T2-test is capable of finding relatively small and robust sets of genes that display different temporal profiles between the conditions of interest. The test is simple, it can be used on gene expression data generated from any experimental design and for any number of conditions, and it allows fast interpretation of the temporal behaviour of genes. The R code is available from V.V. The microarray data have been submitted to GEO under series GSE1574 and GSE3523.

Animals↗

PubMed2006

Production of porcine cloned transgenic embryos expressing green fluorescent protein by somatic cell nuclear transfer.

In the present study, nuclear transferred embryos (NTEs) were reconstructed by using pig fetal fibroblasts as donors and in vitro matured oocytes as recipients. The effects of G418 selection on donor cells, duration of IVM of prepubertal gilt oocytes and oxygen tension in IVM of oocytes were investigated. The results were as follows: (i) When G418 selected cells expressing GFP were used as donors, the cleavage rate of NTEs decreased drastically in comparison to NTEs derived from donors without antibiotic selection (47.5% vs. 71.6%, p < 0.05). For the blastocyst rate, no significant difference was observed between two groups (10% vs. 10.4%, p > 0.05). (ii) The rate of nuclear maturation of oocytes increased significantly when IVM duration time was extended from 36 to 42 h (83.6% vs. 96.7%, p < 0.05). However, no statistical difference was observed between NTEs derived from oocytes of 36 h IVM group and NTEs from oocytes of 42 h IVM group in the rates of cleavage (59.3% vs. 73.6%, p > 0.05) and blastocyst formation (9.3% vs. 13.2%, p > 0.05); (iii) no significant difference was observed between NTEs reconstructed from oocytes matured under lower oxygen (7% O2) tension and NTEs derived from oocytes matured under higher oxygen tension (20% O2) in cleavage rate (70.6% vs. 67.1%, p > 0.05) and blastocyst rate (11.8% vs. 12.3%, p > 0.05). These results suggest that: (i) G418 selection does not have a significant effect on cleavage rate of NTEs expressing GFP. (ii) Nuclear maturation is greatly improved by prolonging IVM duration from 36 to 42 h, while no significant differences were observed for developmental potential of transgenic embryos. Thus IVM 42 h is the better choice in order to obtain maximum number of M II oocytes as recipients. (iii) Lower oxygen tension and higher oxygen tension in IVM have no significant effect on development of cloned embryos.

Animals↗

PubMed2006

Does adenosine deaminase play a key role in coronary artery disease.

Adenosine deaminase (ADA) is an enzyme which catalyzes adenosine to inosine. Patients who inherently lack the enzyme have defects in both humoral and cellular immunity. ADA plays an important role in many immunity mediate diseases, such as asthma, Graves' disease and tuberculosis. Coronary artery disease (CAD) has been considered as an inflammatory and immunizing disease recently. However, there are few reports about the effect of ADA in cardiovascular fields. In fact, ADA may play a key role in the immunity, inflammation and other aspects of CAD. This hypothesis is potentially based on three aspects of evolution. First, ADA inhibitors attenuate the elevation of proinflammatory factors, which shows ADA mediate in the inflammation response. ADA also has effect on the activation of complement system by the deamination of adenosine. Thus, ADA has a role in CAD by affecting inflammation process. Second, many effects produced by ADA are caused by the metabolism of adenosine. It is known that adenosine can inhibit the invasion of the neutrophil so as to attenuate the ischemic/reperfusion injury . Adenosine can increase coronary artery blood flow during active stress and hypoxia to balance the oxygen supply and demand. Adenosine can also account for the majority of basal vascular endothelial growth factor (VEGF) mRNA and protein expression in cultured myocardial vascular smooth muscle cells under normoxic conditions to stimulate the angiogenesis. If adenosine is rapidly metabolized by the high level of ADA, the advantages of adenosine will lost. Finally, adenosine is catalyzed to inosine, which can produce superoxide radicals and exaggerate the ischemic/reperfusion injury. In conclusion ADA can have a crucial role in CAD, if design and development of therapeutic strategies against ADA is guaranteed, an innovational therapeutic approach to CAD can be realized.

Adenosine Deaminase↗

PubMed2006

Stability analysis for stochastic Cohen-Grossberg neural networks with mixed time delays.

In this letter, the global asymptotic stability analysis problem is considered for a class of stochastic Cohen-Grossberg neural networks with mixed time delays, which consist of both the discrete and distributed time delays. Based on an Lyapunov-Krasovskii functional and the stochastic stability analysis theory, a linear matrix inequality (LMI) approach is developed to derive several sufficient conditions guaranteeing the global asymptotic convergence of the equilibrium point in the mean square. It is shown that the addressed stochastic Cohen-Grossberg neural networks with mixed delays are globally asymptotically stable in the mean square if two LMIs are feasible, where the feasibility of LMIs can be readily checked by the Matlab LMI toolbox. It is also pointed out that the main results comprise some existing results as special cases. A numerical example is given to demonstrate the usefulness of the proposed global stability criteria.

Algorithms↗

PubMed2006

Robust Selection of Predictive Genes via a Simple Classifier.

Identifying genes that direct the mechanism of a disease from expression data is extremely useful in understanding how that mechanism works. This in turn may lead to better diagnoses and potentially could lead to a cure for that disease. This task becomes extremely challenging when the data are characterised by only a small number of samples and a high number of dimensions, as is often the case with gene expression data. Motivated by this challenge, we present a general framework that focuses on simplicity and data perturbation. These are the keys for robust identification of the most predictive features in such data. Within this framework, we propose a simple selective naive Bayes classifier discovered using a global search technique, and combine it with data perturbation to increase its robustness for small sample sizes. An extensive validation of the method was carried out using two applied datasets from the field of microarrays and a simulated dataset, all confounded by small sample sizes and high dimensionality. The method has been shown to be capable of selecting genes known to be associated with prostate cancer and viral infections.

Artificial Intelligence↗

PubMed2005

Global exponential stability of generalized recurrent neural networks with discrete and distributed delays.

This paper is concerned with analysis problem for the global exponential stability of a class of recurrent neural networks (RNNs) with mixed discrete and distributed delays. We first prove the existence and uniqueness of the equilibrium point under mild conditions, assuming neither differentiability nor strict monotonicity for the activation function. Then, by employing a new Lyapunov-Krasovskii functional, a linear matrix inequality (LMI) approach is developed to establish sufficient conditions for the RNNs to be globally exponentially stable. Therefore, the global exponential stability of the delayed RNNs can be easily checked by utilizing the numerically efficient Matlab LMI toolbox, and no tuning of parameters is required. A simulation example is exploited to show the usefulness of the derived LMI-based stability conditions.

Artificial Intelligence↗

PubMed2005

Synthesis, crystal structure, and properties of MnNCN, the first carbodiimide of a magnetic transition metal.

Synthesis, single-crystal structure determination, and magnetic properties are reported for manganese carbodiimide, MnNCN. The presumably unstable but inert phase adopts the trigonal system (R3m) with a = 3.3583(4) A, c = 14.347(2) A, V = 140.13(3) A3, and Z = 3. Divalent manganese is octahedrally coordinated by nitrogen atoms at 2.26 A, and the NCN(2-) unit adopts the linear [N=C=N](2-) carbodiimide shape with two C=N double bonds of 1.23 A. MnNCN contains high-spin Mn(II) with five unpaired electrons and behaves like an antiferromagnet with an ordering temperature below 30 K.

Journal Article↗

PubMed2005

Proteomic analysis of mouse liver plasma membrane: use of differential extraction to enrich hydrophobic membrane proteins.

To comprehensively identify proteins of liver plasma membrane (PM), we isolated PMs from mouse liver by sucrose density gradient centrifugation. An optimized extraction method for whole PM proteins and several methods of differential extraction expected to enrich hydrophobic membrane proteins were tested. The extracted PM proteins were separated by 2-DE, and were identified by MALDI-TOF-MS, and ESI-quadrupole-TOF MS. As the complementary method, 1-DE-MS/MS was also used to identify PM proteins. The optimized lysis buffer containing urea, thiourea, CHAPS and NP-40 was able to extract more PM proteins, and treatment of PM samples with chloroform/methanol and sodium carbonate led to enrichment of more hydrophobic PM proteins. From the mouse liver PM fraction, 175 non-redundant gene products were identified, of which 88 (about 50%) were integral membrane proteins with one to seven transmembrane domains. The remaining products were probably membrane-associated and cytosolic proteins. The function distribution of all the identified liver PM proteins was analyzed; 40% represented enzymes, 12% receptors and 9% proteins with unknown function.

Animals↗

PubMed2005

A spatio-temporal Bayesian network classifier for understanding visual field deterioration.

OBJECTIVE: Progressive loss of the field of vision is characteristic of a number of eye diseases such as glaucoma which is a leading cause of irreversible blindness in the world. Recently, there has been an explosion in the amount of data being stored on patients who suffer from visual deterioration including field test data, retinal image data and patient demographic data. However, there has been relatively little work in modelling the spatial and temporal relationships common to such data. In this paper we introduce a novel method for classifying visual field (VF) data that explicitly models these spatial and temporal relationships. METHODOLOGY: We carry out an analysis of our proposed spatio-temporal Bayesian classifier and compare it to a number of classifiers from the machine learning and statistical communities. These are all tested on two datasets of VF and clinical data. We investigate the receiver operating characteristics curves, the resulting network structures and also make use of existing anatomical knowledge of the eye in order to validate the discovered models. RESULTS: Results are very encouraging showing that our classifiers are comparable to existing statistical models whilst also facilitating the understanding of underlying spatial and temporal relationships within VF data. The results reveal the potential of using such models for knowledge discovery within ophthalmic databases, such as networks reflecting the 'nasal step', an early indicator of the onset of glaucoma. CONCLUSION: The results outlined in this paper pave the way for a substantial program of study involving many other spatial and temporal datasets, including retinal image and clinical data.

Algorithms↗

PubMed2005

State estimation for delayed neural networks.

In this letter, the state estimation problem is studied for neural networks with time-varying delays. The interconnection matrix and the activation functions are assumed to be norm-bounded. The problem addressed is to estimate the neuron states, through available output measurements, such that for all admissible time-delays, the dynamics of the estimation error is globally exponentially stable. An effective linear matrix inequality approach is developed to solve the neuron state estimation problem. In particular, we derive the conditions for the existence of the desired estimators for the delayed neural networks. We also parameterize the explicit expression of the set of desired estimators in terms of linear matrix inequalities (LMIs). Finally, it is shown that the main results can be easily extended to cope with the traditional stability analysis problem for delayed neural networks. Numerical examples are included to illustrate the applicability of the proposed design method.

Algorithms↗

PubMed2005

A Weighted Sum Validity Function for clustering with a Hybrid Niching Genetic Algorithm.

Clustering is inherently a difficult problem, both with respect to the construction of adequate objective functions as well as to the optimization of the objective functions. In this paper, we suggest an objective function called the Weighted Sum Validity Function (WSVF), which is a weighted sum of the several normalized cluster validity functions. Further, we propose a Hybrid Niching Genetic Algorithm (HNGA), which can be used for the optimization of the WSVF to automatically evolve the proper number of clusters as well as appropriate partitioning of the data set. Within the HNGA, a niching method is developed to preserve both the diversity of the population with respect to the number of clusters encoded in the individuals and the diversity of the subpopulation with the same number of clusters during the search. In addition, we hybridize the niching method with the k-means algorithm. In the experiments, we show the effectiveness of both the HNGA and the WSVF. In comparison with other related genetic clustering algorithms, the HNGA can consistently and efficiently converge to the best known optimum corresponding to the given data in concurrence with the convergence result. The WSVF is found generally able to improve the confidence of clustering solutions and achieve more accurate and robust results.

Algorithms↗

PubMed2005

Dual regulation of c-Myc by p300 via acetylation-dependent control of Myc protein turnover and coactivation of Myc-induced transcription.

The c-Myc oncoprotein (Myc) controls cell fate by regulating gene transcription in association with a DNA-binding partner, Max. While Max lacks a transcription regulatory domain, the N terminus of Myc contains a transcription activation domain (TAD) that recruits cofactor complexes containing the histone acetyltransferases (HATs) GCN5 and Tip60. Here, we report a novel functional interaction between Myc TAD and the p300 coactivator-acetyltransferase. We show that p300 associates with Myc in mammalian cells and in vitro through direct interactions with Myc TAD residues 1 to 110 and acetylates Myc in a TAD-dependent manner in vivo at several lysine residues located between the TAD and DNA-binding domain. Moreover, the Myc:Max complex is differentially acetylated by p300 and GCN5 and is not acetylated by Tip60 in vitro, suggesting distinct functions for these acetyltransferases. Whereas p300 and CBP can stabilize Myc independently of acetylation, p300-mediated acetylation results in increased Myc turnover. In addition, p300 functions as a coactivator that is recruited by Myc to the promoter of the human telomerase reverse transcriptase gene, and p300/CBP stimulates Myc TAD-dependent transcription in a HAT domain-dependent manner. Our results suggest dual roles for p300/CBP in Myc regulation: as a Myc coactivator that stabilizes Myc and as an inducer of Myc instability via direct Myc acetylation.

Acetylation↗

PubMed2004

Consensus clustering and functional interpretation of gene-expression data.

Microarray analysis using clustering algorithms can suffer from lack of inter-method consistency in assigning related gene-expression profiles to clusters. Obtaining a consensus set of clusters from a number of clustering methods should improve confidence in gene-expression analysis. Here we introduce consensus clustering, which provides such an advantage. When coupled with a statistically based gene functional analysis, our method allowed the identification of novel genes regulated by NFkappaB and the unfolded protein response in certain B-cell lymphomas.

Cluster Analysis↗

PubMed2004

Preparation of single rice chromosome for construction of a DNA library using a laser microbeam trap.

We report the development of a laser micromanipulation system and its application in the isolation of individual rice chromosomes directly from a metaphase cell. Microdissection and flow sorting are two major methods for the isolation of single chromosome. These methods are dependent on the techniques of chromosome spread and chromosome suspension, respectively. In the development of this system, we avoided using chromosome spread and cell suspension was used instead. The cell wall of metaphase rice cell was cut by optical scissors. The released single chromosome was captured by an optical trap and transported to an area without cell debris. The isolated single chromosome was then collected and specific library was constructed by linker adaptor PCR. The average insert size of the library was about 300 bp. Two hundred inserts of chromosome 4 library were sequenced, and 96.5% were aligned to the corresponding sequences of rice chromosome 4. These results suggest the possible application of this method for the preparation of other subcellular structures and for the cloning of single macromolecule through a laser microbeam trap.

Chromosomes, Plant↗

PubMed2003

Experimental and quantum-chemical studies on the thermochemical stabilities of mercury carbodiimide and mercury cyanamide.

Calorimetric dissolution measurements of the solid compounds mercury carbodiimide HgNCN(I) and mercury cyanamide HgNCN(II) in aqueous HCl that targeted at their thermochemical stabilities show the cyanamide species HgNCN(II) to be the more stable phase in terms of both enthalpy and Gibbs energy with an enthalpy difference of 2-3 kJ mol-1. While the stability ranking of HgNCN(I) and HgNCN(II) thus perfectly matches Pearson's HSAB concept, quantum-chemical stability predictions using common parametrizations of density functional theory appear to be fundamentally flawed. An analysis of the error is attempted on the basis of correlated wave functions for related molecules.

Journal Article↗

PubMed2003

c-Myc transformation domain recruits the human STAGA complex and requires TRRAP and GCN5 acetylase activity for transcription activation.

Deregulation of the c-Myc oncoprotein (Myc) is implicated in many types of cancer. Myc is a sequence-specific transcription factor that regulates transcription of genes involved in the control of cell proliferation and apoptosis via mechanisms that are still poorly understood. Cell transformation by Myc involves its association with the transformation-transactivation domain-associated protein (TRRAP) and the human histone acetyltransferase (HAT) GCN5. TRRAP and GCN5 are components of a variety of shared and distinct multiprotein HAT complexes with diverse functions. Myc induces TRRAP recruitment and histone hyperacetylation at specific Myc-activated genes in vivo. However, the identity of the HAT complexes recruited by Myc and the roles of TRRAP and GCN5 in Myc function are still unclear. Here we show that Myc co-recruits TRRAP and GCN5 via direct physical interactions of its N-terminal activation/transformation domain with the human STAGA (SPT3-TAF-GCN5 acetylase) coactivator complex. We demonstrate that GCN5 and TRRAP cooperate to enhance transcription activation by the N-terminal activation domain of Myc in vivo and that this synergy requires both the SPT3/GCN5 interaction domain of TRRAP and the HAT activity of GCN5. Thus, TRRAP might function as an adaptor within the STAGA complex, which helps recruit GCN5 HAT activity to Myc during transcription activation.

Acetylation↗