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Hong Zhang

Publications and source records attributed to Hong Zhang.

At least 181 records · Page 10Linked to original sources
PubMed2005

Prediction of methylated CpGs in DNA sequences using a support vector machine.

DNA methylation plays a key role in the regulation of gene expression. The most common type of DNA modification consists of the methylation of cytosine in the CpG dinucleotide. At the present time, there is no method available for the prediction of DNA methylation sites. Therefore, in this study we have developed a support vector machine (SVM)-based method for the prediction of cytosine methylation in CpG dinucleotides. Initially a SVM module was developed from human data for the prediction of human-specific methylation sites. This module achieved a MCC and AUC of 0.501 and 0.814, respectively, when evaluated using a 5-fold cross-validation. The performance of this SVM-based module was better than the classifiers built using alternative machine learning and statistical algorithms including artificial neural networks, Bayesian statistics, and decision trees. Additional SVM modules were also developed based on mammalian- and vertebrate-specific methylation patterns. The SVM module based on human methylation patterns was used for genome-wide analysis of methylation sites. This analysis demonstrated that the percentage of methylated CpGs is higher in UTRs as compared to exonic and intronic regions of human genes. This method is available on line for public use under the name of Methylator at http://bio.dfci.harvard.edu/Methylator/.

Algorithms↗
PubMed2005

Cecropin P1 and novel nematode cecropins: a bacteria-inducible antimicrobial peptide family in the nematode Ascaris suum.

Cecropin P1 was first identified as a mammalian antimicrobial peptide isolated from the pig intestine. Much research aimed at characterizing this peptide has been reported. Recently, the workers who discovered the peptide corrected their original conclusion, and confirmed that this peptide originates in fact from the pig intestinal parasitic nematode, Ascaris suum. In the present study, we carried out a semi-exhaustive search for bacteria-inducible transcripts in A. suum by the cDNA subtraction method. The transcripts encoding cecropin P1 and novel Ascaris cecropins, designated cecropins P2, P3 and P4, were found to be positively induced factors. Chemically synthesized Ascaris cecropins were bactericidal against a wide range of microbes, i.e. Gram-positive (Staphylococcus aureus, Bacillus subtilis and Micrococcus luteus) and Gram-negative (Pseudomonas aeruginosa, Salmonella typhimurium, Serratia marcescens and Esherichia coli) bacteria, and were weakly but detectably active against yeasts (Saccharomyces cerevisiae and Candida albicans). Cecropin P1-like sequences were also detected at least in two other species (Ascaris lumbricoides and Toxocara canis) of the Ascarididae. All Ascaris cecropin precursors contain an acidic pro-region connected by a tetra-basic cleavage site at the C-terminus. Such an acidic pro-region is also reported to be present in the tunicate cecropin-type antimicrobial peptide styelin. On the basis of the evolutionary position of nematodes and tunicates, the ancestral cecropin may have contained the acidic pro-region at the C-terminus.

Amino Acid Sequence↗
PubMed2005

Spam1-associated transmission ratio distortion in mice: elucidating the mechanism.

BACKGROUND: While transmission ratio distortion, TRD, (a deviation from Mendelian ratio) is extensive in humans and well-documented in mice, the underlying mechanisms are unknown. Our earlier studies on carriers of spontaneous mutations of mouse Sperm Adhesion Molecule 1 (Spam1) suggested that TRD results from biochemically different sperm, due to a lack of transcript sharing through the intercellular cytoplasmic bridges of spermatids. These bridges usually allow transcript sharing among genetically different spermatids which develop into biochemically and functionally equivalent sperm. OBJECTIVES: The goals of the study were to provide support for the lack of sharing (LOS) hypothesis, using transgene and null carriers of Spam1, and to determine the mechanism of Spam1-associated TRD. METHODS: Carriers of Spam1-Hyal5 BAC transgenes were mated with wild-type female mice and the progeny analyzed for TRD by PCR genotyping. Sperm from transgene and Spam1 null carriers were analyzed using flow cytometry and immunocytochemistry to detect quantities of Spam1 and/or Hyal5. Transgene-bearing sperm with Spam1 overexpression were detected by fluorescence in situ hybridization. In wild-type animals, EM studies of in situ transcript hybridization of testis sections and Northern analysis of biochemically fractionated testicular RNA were performed to localize Spam1 transcript. Finally, AU-rich motifs identified in the 3' UTR of Spam1 RNA were assayed by UV cross-linking to determine their ability to interact with testicular RNA binding proteins. RESULTS: The Tg8 line of transgene carriers had a significant (P < 0.001) TRD, due to reduced fertilizing ability of transgene-bearing sperm. These sperm retained large cytoplasmic droplets engorged with overexpressed Spam1 or Hyal5 protein. Caudal sperm from transgene carriers and caput sperm of null carriers showed a bimodal distribution of Spam1, indicating that the sperm in a male were biochemically different with respect to Spam1 quantities. Spam1 RNA was absent from the bridges, associated exclusively with the ER, and was shown to be anchored to the cytoskeleton. This compartmentalization of the transcript, mediated by cytoskeletal binding, occurs via protein interactions with 3' UTR AU-rich sequences that are likely involved in its stabilization. CONCLUSION: We provide strong support for the LOS hypothesis, and have elucidated the mechanism of Spam1-associated TRD.

Alleles↗
PubMed2005

Regulation of lipopolysaccharide-induced inflammatory response by glutathione S-transferase P1 in RAW264.7 cells.

Glutathione S-transferase P1(GSTP1) plays an important role in the detoxification and xenobiotics metabolism. Here, we show that GSTP1 is also involved in LPS (lipopolysaccharide)-induced inflammatory response. GSTP1 expression, determined at the transcription and translation levels, were upregulated by the LPS stimulation in RAW264.7 macrophage-like cells. GSTP1 inhibited LPS-induced mitogen-activated protein kinases MAPKs including ERK, JNK and p38 as well as NF-kappaB activation dose- and time-dependently in transient transfected and stable transfected cells. Moreover this inhibition of the signaling pathways resulted in the decrease of tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO) synthesis. These data suggest that the GSTP1 prevents LPS-induced excessive production of pro-inflammatory factors and plays an anti-inflammatory role in response to LPS.

Animals↗
PubMed2005

Improved rapid amplification of cDNA ends (RACE) for mapping both the 5' and 3' terminal sequences of paramyxovirus genomes.

Rapid amplification of cDNA ends (RACE) is a powerful PCR-based technique for determination of RNA terminal sequences. However, most of the RACE methods reported in the literature are developed specifically for the mapping of eukaryotic transcripts with 3' poly-A tail and 5' cap structure. In this study, an improved RACE strategy was developed which allows both 5' and 3' RACE of paramyxovirus genomic RNA using the same set of common molecular biology reagents without having to rely on expensive RACE kits. Mapping of RNA genome terminal sequences is an essential part of characterizing novel paramyxoviruses since these sequences contain important signals for genome replication and transcription, and are important molecular markers for studying virus evolution. The usefulness of this strategy was demonstrated by rapid characterization of both genome ends for a novel paramyxovirus recently isolated from human kidney primary cells. The RACE strategy described in this paper is simple, cost-effective and can be used to map genome ends of any RNA viruses.

DNA Primers↗
PubMed2005

[Carrier rate of Streptococcus pneumoniae and susceptibility thereof to antimicrobial drugs among children in China: a surveillance study in Beijing, Shanghai, and Guangzhou 2000-2002].

OBJECTIVE: To investigate the carrier rate of Streptococcus pneumoniae and the susceptibility of S. pneumoniae to 10 different antimicrobial drugs among children in China. METHODS: Nasopharageal swab specimens were collected from randomly selected 3578 out-patients with upper respiratory infection aged 1 month to 5 years in Beijing, Shanghai, and Guangzhou 2000-2002 so as to isolate S. pneumoniae. The susceptibility of these strains to erythromycin and beta-lactam antibiotics (penicillin, amoxicillin/clavulanic acid, cefaclor, cefuroxime and ceftriaxone) was determinated by E-test MIC method, and the susceptibility to chloramphenicol, tetracycline, sulfamethoxazole/trimethoprim and ciprofloxacin was determinated by disk diffusion method. RESULTS: A total of 892 strains of S. pneumoniae were isolate from the 3578 children with a carrier rate of 24.9% (9.0%-36.0%). 634 isolates of S. pneumoniae were tested to examine their susceptibility to chloramphenicol, 199 to ciprofloxacin, and 887 to the other 8 antimicrobial drugs. The insusceptibility rate of S. pneumoniae to penicillin was 39.9%, and the resistance rate was 6.4%. The resistance rate to cefaclor was 20.4%. The insusceptibility rate to cefuroxime was 19.0%. The susceptibility rate to amoxicillin/clavulanic acid was 98.5% and that to ceftriaxone was 97.2%. More than 80% of the isolates were resistant to erythromycin, tetracycline, and sulphamethoxazole/trimethoprim. Chloramphenicol resistance was less common (32.3%) than the resistance to other non-beta-lactam antibiotics, except for ciprofloxacin to which the resistance rate was 2.0%. The national insusceptibility rates for beta-lactam antibiotics did not vary significantly during the three years with the widest varying range of 5.1% for penicillin (38.1%-43.2%). Each of the three cities had their different varying patterns of antimicrobial susceptibility, especially for beta-lactam antibiotics. Multi-drug resistance was common (88.7%). Strains of S. pneumoniae insusceptible to penicillin were significantly more common than those susceptible to penicillin (99.1% vs. 78.8%, chi(2) = 50.36, P < 0.001), and strains of S. pneumoniae insusceptible to erythromycin were significantly more common than those susceptible to erythromycin too (95.8% vs. 17.1%, chi(2) = 360.26, P < 0.001). CONCLUSION: Antimicrobial resistant S. pneumoniae has already become a serious problem in China. Ongoing surveillance study on the antimicrobial resistance of S. pneumoniae is necessary for appropriate antimicrobial use in clinical work and modification of medical strategies for people's health.

Anti-Bacterial Agents↗
PubMed2005

Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity.

There is a rapid global rise in obesity, and the link between obesity and diabetes remains somewhat obscure. We identified an adipocytokine, designated as visceral adipose tissue-derived serpin (vaspin), which is a member of serine protease inhibitor family. Vaspin cDNA was isolated by from visceral white adipose tissues (WATs) of Otsuka Long-Evans Tokushima fatty (OLETF) rat, an animal model of abdominal obesity with type 2 diabetes. Rat, mouse, and human vaspins are made up of 392, 394, and 395 amino acids, respectively; exhibit approximately 40% homology with alpha1-antitrypsin; and are related to serine protease inhibitor family. Vaspin was barely detectable in rats at 6 wk and was highly expressed in adipocytes of visceral WATs at 30 wk, the age when obesity, body weight, and insulin levels peak in OLETF rats. The tissue expression of vaspin and its serum levels decrease with worsening of diabetes and body weight loss at 50 wk. The expression and serum levels were normalized with the treatment of insulin or insulin-sensitizing agent, pioglitazone, in OLETF rats. Administration of vaspin to obese CRL:CD-1 (ICR) (ICR) mice fed with high-fat high-sucrose chow improved glucose tolerance and insulin sensitivity reflected by normalized serum glucose levels. It also led to the reversal of altered expression of genes relevant to insulin resistance, e.g., leptin, resistin, TNFalpha, glucose transporter-4, and adiponectin. In DNA chip analyses, vaspin treatment resulted in the reversal of expression in approximately 50% of the high-fat high-sucrose-induced genes in WATs. These findings indicate that vaspin exerts an insulin-sensitizing effect targeted toward WATs in states of obesity.

Adipocytes↗
PubMed2005

Differential involvement of the related DNA helicases Pif1p and Rrm3p in mtDNA point mutagenesis and stability.

With the exception of base excision repair, conserved pathways and mechanisms that maintain mitochondrial genome stability have remained largely undelineated. In the budding yeast, Saccharomyces cerevisiae, Pif1p is a unique DNA helicase that is localized both to the nucleus and mitochondria, where it is involved in maintaining DNA integrity. We previously elucidated a role for Pif1p in oxidative mtDNA damage resistance that appears to be distinct from its postulated function in mtDNA recombination. Strains lacking Pif1p (pif1Delta) exhibit an increased rate of formation of petite mutants (an indicator of mtDNA instability) and elevated mtDNA point mutagenesis. Here we show that deletion of the RRM3 gene, which encodes a DNA helicase closely related to Pif1p, significantly rescues the petite-induction phenotype of a pif1Delta strain. However, suppression of this phenotype was not accompanied by a corresponding decrease in mtDNA point mutagenesis. Instead, deletion of RRM3 alone resulted in an increase in mtDNA point mutagenesis that was synergistic with that caused by a pif1Delta mutation. In addition, we found that over-expression of RNR1, encoding a large subunit of ribonucleotide reductase (RNR), rescued the petite-induction phenotype of a pif1Delta mutation to a similar extent as deletion of RRM3. This, coupled to our finding that the Rad53p protein kinase is phosphorylated in the rrm3Delta pif1Delta double-mutant strain, leads us to conclude that one mechanism whereby deletion of RRM3 influences mtDNA stability is by modulating mitochondrial deoxynucleoside triphosphate pools. We propose that this is accomplished by signaling through the conserved Mec1/Rad53, S-phase checkpoint pathway to induce the expression and activity of RNR. Altogether, our results define a novel role for Rrm3p in mitochondrial function and indicate that Pif1p and Rrm3p influence a common process (or processes) involved in mtDNA replication, repair, or stability.

Blotting, Western↗
PubMed2005

Unimolecular rovibrational bound and resonance states for large angular momentum: J=20 calculations for HO2.

We explore the calculation of unimolecular bound states and resonances for deep-well species at large angular momentum using a Chebychev filter diagonalization scheme incorporating doubling of the autocorrelation function as presented recently by Neumaier and Mandelshtam [Phys. Rev. Lett. 86, 5031 (2001)]. The method has been employed to compute the challenging J=20 bound and resonance states for the HO2 system. The methodology has firstly been tested for J=2 in comparison with previous calculations, and then extended to J=20 using a parallel computing strategy. The quantum J-specific unimolecular dissociation rates for HO2-->H+O2 in the energy range from 2.114 to 2.596 eV have been reported for the first time, and comparisons with the results of Troe and co-workers [J. Chem. Phys. 113, 11019 (2000) Phys. Chem. Chem. Phys. 2, 631 (2000)] from statistical adiabatic channel method/classical trajectory calculations have been made. For most of the energies, the reported statistical adiabatic channel method/classical trajectory rate constants agree well with the average of the fluctuating quantum-mechanical rates. Near the dissociation threshold, quantum rates fluctuate more severely, but their average is still in agreement with the statistical adiabatic channel method/classical trajectory results.

Journal Article↗
PubMed2005

[The effect of posttreatment with isoflurane versus propofol on pulmonary alveolar capillary barrier in endotoxemic rats].

OBJECTIVE: To compare the effects of posttreatment with isoflurane versus propofol on pulmonary alveolar capillary barrier (PACB) in endotoxemic rats. METHODS: Ninety-six male Sprague-Dawley rats weighing 250 to 350 g were randomly divided into 6 equal groups to be administered with intravenous lipopolysaccharide (LPS, 4 mg/kg) or equivalent volume of normal saline (NS) and treated with intravenous pentobarbital (C, 20 mg x kg(-1) x h(-1)), inhaled isoflurane (I, 0.55%) or intravenous propofol (P, 10 mg/kg bolus, 40 mg x kg(-1) x h(-1)) 2 hours after the establishment of endotoxemic model: NS-C, NS-I, NS-P, LPS-C, LPS-I, and LPS-P groups. The rats were ventilated for 2 h. The mean arterial pressure (MAP) and arterial blood gas were assessed hourly for 4 h. One cohort (n = 8 per group) was subjected to bronchial alveolar lavage in the left lungs for determination of protein concentration in the bronchial alveolar lavage fluid (BALF) and the lung permeability index (LPI, BALF protein concentration/serum protein concentration). Then the right lungs were removed to undergo light and electron microscopy and measurement of the wet wet-to-dry weight ratio (WW/WD). In a second cohort (n = 8 per group), Evans blue dye (EBD, 30 mg/kg) was injected 30 min before the end of the experiment to determine the EBD content in the lung. RESULTS: The MAP, pH, PaCO(2), and PaO(2) were not different significantly within the three NS groups and the three LPS groups and WW/WD did not show any difference among all six groups. The LPI and EBD content in lung were significantly higher in the LPS-C group [8.1 x 10(-3) +/- 2.4 x 10(-3) and 0.628 +/- 0.082 absorption unit (AU) respectively] than in NS-C group (3.3 x 10(-3) +/- 2.2 x 10(-3) and 0.479 +/- 0.154 AU respectively, both P < 0.05), and were higher in the LPS-P group (9.1 x 10(-3) +/- 2.2 x 10(-3) and 0.664 +/- 0.028 AU respectively) than in the LPS-I group (5.5 x 10(-3) +/- 2.0 x 10(-3) and 0.517 +/- 0.048 AU respectively, both P < 0.05). Light microscopy showed more severe lung injury changes in the LPS groups than in the NS groups, especially in the LPS-P group. Electron microscopy found that the tight junctions between the adjacent pulmonary microvascular endothelial cells in the LPS-P groups were disrupted. CONCLUSION: Compared with posttreatment with propofol, posttreatment with isoflurane protects the PACB function and decreases the pulmonary permeability in endotoxemic rats.

Animals↗
PubMed2005

Diurnal variation of dissolved gaseous mercury (DGM) levels in a southern reservoir lake (Tennessee, USA) in relation to solar radiation.

Variations of dissolved gaseous mercury (DGM) concentrations in a southern reservoir lake (Cane Creek Lake, Cookeville, TN, USA) in relation to solar radiation were investigated consecutively from June 2003 to May 2004. The daytime DGM levels in the lake exhibited a two-phase diurnal trend; the DGM concentrations rose in the morning, peaked around noontime and then fell in the afternoon through the evening; these trends followed the general pattern of diurnal solar radiation variations. The morning and afternoon phases appeared to be asymmetrical with the former relatively steep and the latter gradual. A variety of daytime DGM level variations other than the typical two-phase diurnal patterns were also observed. For the time spans studied, the daytime mean DGM concentrations of the lake ranged from 12 to 68 pg L(-1) (60-340 fM). The daytime mean DGM levels in the summertime (June, July, August) showed values above 30 pg L(-1) (150 fM) in most cases and a large number of peak DGM concentrations above 50 pg L(-1) (250 fM). The summer DGM levels in the lake appear to be comparable to those observed in the large northern lakes for the summertime. The daytime DGM levels in the lake were found to correlate with solar radiation to various degrees (cases of r values above 0.8: approximately 12% and approximately 18% of the total sampling days for correlation with global solar radiation and UVA radiation, respectively). Correlating trends are recognizable between the daytime mean DGM concentration and the corresponding mean global solar radiation (r = 0.66, p < 0.0005) and between the daytime mean DGM concentration and the corresponding mean UVA radiation (r = 0.62, p < 0.0005).

Environmental Monitoring↗
PubMed2005

Current status of tumor radiogenic therapy.

Although tumor gene therapy falls behind its clinical use, the combination of irradiation and gene therapy is full of promise in cancer therapy based on traditional radiotherapy, chemotherapy and surgery. We have termed it as radiogenic therapy. This review focuses on the following aspects of radiogenic therapy in recent years: improvement of gene transfer efficiency by irradiation, radiotherapy combined with cytokine gene delivery or enhancement of the immunity of tumor cells by transgene, direct stimulation by radiation to produce cytotoxic agents, increase of tumor cell radiosensitivity in gene therapy by controlling the radiosensitivity genes and adjusting the fraction dose and interval of radiation so as to achieve the optimum antitumor effect while reducing the normal tissue damage, radioprotective gene therapy enhancing radiation tumor killing effect while protecting the normal tissue and organs with transgene using transfer vectors.

Genetic Therapy↗
PubMed2005

Submucous colon lipoma: a case report and review of the literature.

Colon lipoma is remarkably rare in clinical practice. We reported a case of ascending colon lipoma in an 83-year-old woman. She was asymptomatic with a lipoma of 35 mm x 30 mm x 24 mm in size which was found by routine colonoscopy. Right hemicolectomy was performed uneventfully. The diagnosis was made by histological examination. Reviewing the literature and combining with our experience, we discussed the clinical features, diagnosis and treatment of this uncommon disease.

Aged↗
PubMed2005

[Variable number of tandem repeats polymorphism of MUC20 is associated with the progression of IgA nephropathy].

OBJECTIVE: The MUC20 gene is a novel up-regulated gene that was identified in renal tissues of patients with IgA nephropathy (IgAN) by restriction endonucleolytic analysis of differentially expressed sequences. The variable number of tandem repeats (VNTR) polymorphism of MUC20 was detected in different cell lines. In this study we determined the distribution of MUC20 VNTR polymorphism in the healthy population, and the association between the MUC20 VNTR polymorphism and the pathogenesis or progression of IgAN. METHODS: 282 healthy and 503 proved IgAN patients by biopsy were involved in this investigation. 113 patients had been followed-up for 3.5 +/- 1.5 years. Genomic DNAs were extracted from peripheral blood leucocytes. MUC20 VNTR polymorphism was detected by PCR amplification and several representational PCR products were confirmed by sequencing. The MUC20 genes were divided into small alleles (repeat times 3) according to the repeat times of MUC20 VNTR. These patients were classified into group SS, SL and LL. MUC20 allele frequencies and genotypes of IgAN patients were analyzed and compared with healthy population. In addition, the associations of MUC20 polymorphism with the clinical and pathological parameters at the time of renal biopsy were analyzed. The data followed up in different groups were compared. RESULTS: There was MUC20 VNTR polymorphism in healthy population with 2 - 6 repeats. The repeat fragment was 57bp. The most frequent alleles included 3(R(3)) and 4(R(4)) repeats; otherwise the least ones included 6(R(6)) repeats. The most frequent genotype was R(3)R(4), then R(3)R(3) and R(4)R(4); the least ones were R(2)R(2), R(3)R(6) and R(5)R(5). The frequencies of MUC20 alleles and genotypes in the IgAN patients were similar to healthy population. Initial ages, blood pressure, proteinuria, and renal function did not differ significantly among the three groups. There was no difference of the urinary osmotic pressure, urinary NAG (N-acetyl-B-D-glucosaminidase) and alpha1 microglobulin (alpha1-MG), and the semiquantitative scores of renal interstitial fibrosis and tubular atrophy in the three groups. IgAN patients with SL/LL genotype had higher odds ratio for progression of renal function (OR = 7.29, 95% CI: 1.68 - 31.60, P = 0.008) than the SS genotype. CONCLUSIONS: There were MUC20 VNTR polymorphisms in the healthy population. The polymorphism did not associate with the pathogenesis and the clinico-pathological parameters at the time of renal biopsy. The SL/LL genotype was likely to be a risk factor for rapid progression of renal function in the patients with IgAN.

Adolescent↗
PubMed2005

Potent activity of a novel dimeric heat shock protein 90 inhibitor against head and neck squamous cell carcinoma in vitro and in vivo.

Heat shock protein 90 (Hsp90) is a molecular chaperone that promotes the conformational maturation of numerous client proteins, many of which play critical roles in tumor cell growth and survival. The ansamycin-based Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) is currently in phase I/II clinical testing. However, 17-AAG is difficult to formulate and displays weak activity against some tumors. A novel dimeric ansamycin, EC5, was evaluated for antitumor activity in eight head and neck squamous cell carcinoma (HNSCC) cell lines. Both 17-AAG and EC5 inhibited tumor cell proliferation effectively, but EC5 was more potent, with IC(50) below 200 nmol/L in most cell lines tested, including several lines that were resistant to 17-AAG. The inability of 17-AAG to kill JHU12 cells was linked to a defect in retinoblastoma signaling and could be rescued by ectopic expression of p16(INK4a). EC5 induced G(1) growth arrest of tumor cells and apoptosis, with the degradation of client proteins including epidermal growth factor receptor, c-Raf-1, Akt, and Cdk4 and inhibition of Akt phosphorylation. In vivo, EC5 dramatically reduced the growth rate of established HNSCC xenografts in nude mice and decreased expression of epidermal growth factor receptor and Akt within the xenografts. These results suggest that this novel ansamycin-based Hsp90 inhibitor affects multiple pathways involved in tumor development and progression and may represent a new strategy for the treatment of HNSCC patients.

Animals↗
PubMed2005

Noggin and bFGF cooperate to maintain the pluripotency of human embryonic stem cells in the absence of feeder layers.

Human embryonic stem (hES) cells are typically maintained on mouse embryonic fibroblast (MEF) feeders or with MEF-conditioned medium. However, these xenosupport systems greatly limit the therapeutic applications of hES cells because of the risk of cross-transfer of animal pathogens. Here we showed that the bone morphogenetic protein antagonist noggin is critical in preventing differentiation of hES cells in culture. Furthermore, we found that the combination of noggin and basic fibroblast growth factor (bFGF) was sufficient to maintain the prolonged growth of hES cells while retaining all hES cell features. Since both noggin and bFGF are expressed in MEF, our findings suggest that they may be important factors secreted by MEF for maintaining undifferentiated pluripotent hES cells. Our data provide new insight into the mechanism how hES cell self-renewal is regulated. The newly developed feeder-free culture system will provide a more reliable alternative for future therapeutic applications of hES cells.

Animals↗
PubMed2005

Suppress Winfree turbulence by local forcing excitable systems.

The occurrence of Winfree turbulence is currently regarded as one of the principal mechanisms underlying cardiac fibrillation. We develop a local stimulation method that suppresses Winfree turbulence in three-dimensional excitable media. We find that Winfree turbulence can be effectively suppressed by locally injecting periodic signals to only a very small subset (around some surface region) of total space sites. Our method for the first time demonstrates the effectiveness of local low-amplitude periodic excitations in suppressing turbulence in 3D excitable media and has fundamental improvements in efficiency, convenience, and turbulence suppression speed compared with previous strategies. Therefore, it has great potential for developing into a practical low-amplitude defibrillation approach.

Animals↗