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Biomedical subjects

Feng Luo

Publications and source records attributed to Feng Luo.

At least 19 recordsLinked to original sources
PubMed2006

Modular organization of protein interaction networks.

MOTIVATION: Accumulating evidence suggests that biological systems are composed of interacting, separable, functional modules. Identifying these modules is essential to understand the organization of biological systems. RESULT: In this paper, we present a framework to identify modules within biological networks. In this approach, the concept of degree is extended from the single vertex to the sub-graph, and a formal definition of module in a network is used. A new agglomerative algorithm was developed to identify modules from the network by combining the new module definition with the relative edge order generated by the Girvan-Newman (G-N) algorithm. A JAVA program, MoNet, was developed to implement the algorithm. Applying MoNet to the yeast core protein interaction network from the database of interacting proteins (DIP) identified 86 simple modules with sizes larger than three proteins. The modules obtained are significantly enriched in proteins with related biological process Gene Ontology terms. A comparison between the MoNet modules and modules defined by Radicchi et al. (2004) indicates that MoNet modules show stronger co-clustering of related genes and are more robust to ties in betweenness values. Further, the MoNet output retains the adjacent relationships between modules and allows the construction of an interaction web of modules providing insight regarding the relationships between different functional modules. Thus, MoNet provides an objective approach to understand the organization and interactions of biological processes in cellular systems. AVAILABILITY: MoNet is available upon request from the authors.

Algorithms↗
PubMed2006

Population genetics and linkage analysis of loci within the FCT region of Streptococcus pyogenes.

The FCT regions of Streptococcus pyogenes strains encode a variety of cell wall-anchored surface proteins that bind the extracellular matrix of the human host and/or give rise to pilus-like appendages. Strong linkage is evident between transcription-regulatory loci positioned within the FCT and emm regions and the emm pattern genotype marker for preferred infection of the throat or skin. These findings provide a basis for the hypothesis that FCT region gene products contribute to tissue-specific infection. In an initial series of steps to address this possibility, the FCT regions of 13 strains underwent comparative sequence analysis, the gene content of the FCT region was characterized for 113 strains via PCR, and genetic linkage was assessed. A history of extensive recombination within FCT regions was evident. The emm pattern D-defined skin specialist strains were highly homogenous in their FCT region gene contents, whereas the emm pattern A-C-defined throat specialist strains displayed a greater variety of forms. Most pattern A-C strains harbored prtF1 (75%) but lacked cpa (75%). In contrast, the majority of emm pattern D strains had cpa (92%) but lacked prtF1 (79%). Models based on FCT and emm region genotypes revealed the most parsimonious pathways of evolution. Using niche-determining candidate genes to infer phylogeny, emm pattern E strains--the so-called generalists, which lack a strong tissue site preference--occupied a transition zone separating most throat specialists from skin specialists. Overall, population genetic analysis supports the possibility that the FCT region gives rise to surface proteins that are largely necessary, but not always sufficient, to confer tissue site preference for infection.

Evolution, Molecular↗
PubMed2006

Role of streptococcal T antigens in superficial skin infection.

FCT region genes of Streptococcus pyogenes encode surface proteins that include fibronectin- and collagen-binding proteins and the serological markers known as T antigens, some of which give rise to pilus-like appendages. It remains to be established whether FCT region surface proteins contribute to virulence by in vivo models of infection. In this study, a highly sensitive and ecologically relevant humanized mouse model was used to measure superficial skin infection. Three genes encoding FCT region surface proteins essential for T-serotype specificity were inactivated. Both the Deltacpa and DeltaprtF2 mutants were highly attenuated for virulence when topically applied to the skin following exponential growth but were fully virulent when delivered in stationary phase. In contrast, the DeltafctA mutant was virulent at the skin, regardless of its initial growth state. Immunoblots of cell extracts revealed anti-FctA-reactive, ladder-like polymers characteristic of streptococcal pili. In addition, FctA formed a heteropolymer with the putative collagen-binding protein Cpa. The DeltafctA mutant showed a loss in anti-Cpa-reactive polymers, whereas anti-FctA-reactive polymers were reduced in the Deltacpa mutant. The findings suggest that both FctA and Cpa are required for pilus formation, but importantly, an intact pilus is not essential for Cpa-mediated virulence. Although it is an integral part of the T-antigen complex, the fibronectin-binding protein PrtF2 is not covalently linked to the FctA- and Cpa-containing heteropolymer derived from cell extracts. The data provide direct evidence that streptococcal T antigens function as virulence factors in vivo, but they also reveal that a pilus-like structure is not essential for the most common form of streptococcal skin disease.

Animals↗
PubMed2006

Perpendicular magnetic anisotropy induced by tetragonal distortion of FeCo alloy films grown on Pd(001).

We grew tetragonally distorted FexCo1-x alloy films on Pd(001). Theoretical first-principles calculations for such films predicted a high saturation magnetization and a high uniaxial magnetic anisotropy energy for specific values of the lattice distortion c/a and the alloy composition x. The magnetic anisotropy was investigated using the magneto-optical Kerr effect. An out-of-plane easy axis of magnetization was observed for Fe0.5Co0.5 films in the thickness range of 4 to 14 monolayers. The magnetic anisotropy energy induced by the tetragonal distortion is estimated to be almost 2 orders of magnitude larger than the value for bulk FeCo alloys. Using LEED Kikuchi patterns, a change of the easy axis of magnetization can be related to a decrease of the tetragonal distortion with thickness.

Journal Article↗
PubMed2006

Application of random matrix theory to microarray data for discovering functional gene modules.

We show that spectral fluctuation of coexpression correlation matrices of yeast gene microarray profiles follows the description of the Gaussian orthogonal ensemble (GOE) of the random matrix theory (RMT) and removal of small values of the correlation coefficients results in a transition from the GOE statistics to the Poisson statistics of the RMT. This transition is directly related to the structural change of the gene expression network from a global network to a network of isolated modules.

Algorithms↗
PubMed2006

Hemodynamic and metabolic changes induced by cocaine in anesthetized rat observed with multimodal functional MRI.

RATIONALE: Physiological changes (such as heart rate and respiration rate) associated with strong pharmacological stimuli could change the blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) mapping signals, independent of neural activity. OBJECTIVES: This study investigates whether the physiological changes per se associated with systemic cocaine administration (1 mg/kg) contaminate the BOLD fMRI signals by measuring BOLD and cerebral blood flow (CBF) fMRI and estimating the cerebral metabolic rate of oxygen (CMRO(2)) changes. MATERIALS AND METHODS: BOLD and CBF fMRI was performed, and changes in CMRO(2) were estimated using the BOLD biophysical model. RESULTS: After systemic cocaine administration, blood pressure, heart rate, and respiration rate increased, fMRI signals remained elevated after physiological parameters had returned to baseline. Cocaine induced changes in the BOLD signal within regions of the reward pathway that were heterogeneous and ranged from -1.2 to 5.4%, and negative changes in BOLD were observed along the cortical surface. Changes in CBF and estimated CMRO(2) were heterogeneous and positive throughout the brain, ranging from 14 to 150% and 10 to 55%, respectively. CONCLUSIONS: This study demonstrates a valuable tool to investigate the physiological and biophysical basis of drug action on the central nervous system, offering the means to distinguish the physiological from neural sources of the BOLD fMRI signal.

Algorithms↗
PubMed2006

Molecular dissection of venom from Chinese scorpion Mesobuthus martensii: identification and characterization of four novel disulfide-bridged venom peptides.

Scorpion venom is composed of a large repertoire of biologically active polypeptides. However, most of these peptides remain to be identified and characterized. In this paper, we report the identification and characterization of four novel disulfide-bridged venom peptides (named BmKBTx, BmKITx, BmKKx1 and BmKKx2, respectively) from the Chinese scorpion, Mesobuthus martensii (also named Buthus martensii Karsch). BmKBTx is composed of 58 amino acid residues and cross-linked by three disulfide bridges. The sequence of BmKBTx shows some similarities to that of the toxin, birtoxin, and its analogs. It is likely that BmKBTx is a beta-toxin active on Na+ channels, which is toxic to either insects or mammals. BmKITx is composed of 71 amino acid residues with four disulfide bridges. It is the longest venom peptide identified from M. martensii so far. BmKITx shows little sequence identity with scorpion alpha-toxins toxic to insects. It is likely that BmKITx is a new type of Na+ -channel specific toxin active on both insects and mammals. BmKKx1 contains 38 amino acid residues cross-linked by three disulfide bridges and shows 84% sequence identity with BmTx3, an inhibitor of A-type K+ channel and HERG currents. BmKKx1 has been classified as alpha-KTx-15.8. BmKKx2 is composed of 36 residues and stabilized by three disulfide bridges. BmKKx2 is a new member of the gamma-K+ -channel toxin subfamily (classified as gamma-KTx 2.2). The venoms of scorpions thus continue to provide novel toxins with potential novel actions on targets.

Amino Acid Sequence↗
PubMed2006

Serum tumor markers for detection of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors and is the second most common cause of cancer death in China. Therefore, it is very important to detect this disease and the recurrence at its earlier period. Serum tumor markers, as the effective method for detecting hepatocellular carcinoma for a long time, could be divided into 4 categories: oncofetal antigens and glycoprotein antigens; enzymes and isoenzymes; genes; and cytokines. Serum alpha fetoprotein (AFP) is the most widely used tumor marker in detecting patients with hepatocellular carcinoma, and has been proven to have capability of prefiguring the prognosis. However, it has been indicated that AFP-L3 and DCP excel AFP in differentiating hepatocellular carcinoma from nonmalignant hepatopathy and detecting small hepatocellular carcinoma. Some tumor markers, such as human cervical cancer oncogene and human telomerase reverse transcriptase mRNA, have also been indicated to have higher accuracies than AFP. Furthermore, some other tumor markers, such as glypican-3, gamma-glutamyl transferase II, alpha-l-fucosidase, transforming growth factor-beta1, tumor-specific growth factor, have been indicated to be available supplementaries to AFP in the detection. AFP mRNA has been shown to correlate with the metastasis and recurrence of HCC, and it may be the most useful marker to prefigure the prognosis. Some other markers, such as gamma-glutamyl transferase mRNA, vascular endothelial growth factor, and interleukin-8, could also be used as available prognostic indicators, and the simultaneous determination of AFP and these markers may detect the recurrence of HCC at its earlier period.

Antigens, Neoplasm↗
PubMed2006

Downregulation of human Cdc6 protein using a lentivirus RNA interference expression vector.

Eukaryotic CDC6 gene function is required for the initiation of DNA replication and is a key regulatory protein during cell cycle progression. The human CDC6 gene is not expressed in most normal tissues, in contrast with its marked expression in proliferating cancer cells. An effective way to explore the gene functions of CDC6 is to knock-down the CDC6 messenger RNA (mRNA) and examine the phenotypic consequences. In this chapter, we describe the construction of a lentivirus vector to express a CDC6 DNA segment. The transcript is able to fold by itself because the sense and antisense regions are complementary. There is a 9-nucleotide (nt) loop region allowing for the short hairpin RNA (shRNA) to form. Cellular ribonucleases process the shRNA into a functional short interfering RNA (siRNA). Down-regulation of Cdc6 protein is confirmed by Western blots.

Cell Cycle Proteins↗
PubMed2005

Characterization of a novel cDNA encoding a short venom peptide derived from venom gland of scorpion Buthus martensii Karsch: trans-splicing may play an important role in the diversification of scorpion venom peptides.

A novel cDNA clone (named BmKT-u) which is a hybrid molecule of the 5'-terminal region of BmKT' cDNA and the 3'-terminal region of an undocumented cDNA (named BmKu), was isolated from a cDNA library made from the venom gland of scorpion Buthus martensii Karsch. BmKT-u codes for a 30 amino acid residue precursor peptide composed of a 20-residue signal sequence, and a putative 10-residue novel mature peptide. Northern blot hybridization showed BmKT-u cDNA is generated from a transcript. RT-PCR experiments excluded the possibility that BmKT-u cDNA is an artifact generated during reverse transcription. Genomic amplifications performed with three pairs of BmKT-u gene-specific primers showed the BmKT-u gene does not exist in the genome of the scorpion as a single transcriptional unit. Genomic cloning for BmKT' showed that the BmKT' gene contains an intron of 509 bp inserted into the region encoding the C-terminal region of the signal peptide. A sequence alignment comparison of the cDNA of BmKT-u with genomic BmKT' revealed that the junction site of the hybrid molecule is located at the 5'-splicing site of the intron. The data suggest that the BmKT-u transcript is a naturally occurring mature mRNA that is generated by trans-splicing. Trans-splicing may contribute to the diversity of venom peptides from venomous animals.

Amino Acid Sequence↗
PubMed2005

Genomic sequence analysis and organization of BmKalphaTx11 and BmKalphaTx15 from Buthus martensii Karsch: molecular evolution of alpha-toxin genes.

Based on the reported cDNA sequences of BmKalphaTxs , the genes encoding toxin BmKalphaTx11 and BmKalphaTx15 were amplified by PCR from the Chinese scorpion Buthus martensii Karsch genomic DNA employing synthetic oligonucleotides. Sequences analysis of nucleotide showed that an intron about 500 bp length interrupts signal peptide coding regions of BmKalphaTx11 and BmKalphaTx15. Using cDNA sequence of BmKalphaTx11 as probe, southern hybridization of BmK genome total DNA was performed. The result indicates that BmKalphaTx11 is multicopy genes or belongs to multiple gene family with high homology genes. The similarity of BmKalpha-toxin gene sequences and southern hybridization revealed the evolution trace of BmKalpha-toxins: BmKalpha-toxin genes evolve from a common progenitor, and the genes diversity is associated with a process of locus duplication and gene divergence.

Amino Acid Sequence↗
PubMed2005

Genomic organization of four novel nondisulfide-bridged peptides from scorpion Mesobuthus martensii Karsch: gaining insight into evolutionary mechanism.

At least 25 nondisulfide-bridged peptides (NDBPs) have been identified and characterized from scorpions. However, the genomic organization of the genes that encode these peptides have not been reported yet. BmKa1, BmKa2 and BmKb1 are three novel genes that code for NDBPs identified by our group from Mesobuthus martensii Karsch. Based on their cDNA sequences, the genomic DNA sequences encoding these peptides were obtained using the PCR method. Sequence analysis showed that three distinct genomic structural patterns are used to encode these three peptides. The BmKa1 gene is not interrupted by any introns. However, the BmKa2 gene is composed of two exons, interrupted by a 67 bp intron that is located in the DNA region encoding the mature peptide. Two genomic homologues of the BmKb1 cDNA sequence, named BmKb1' and BmKb2, respectively, were obtained. The BmKb1' gene contains one intron of 593 bp, inserted into the DNA region that encodes the signal peptide. Similarly, the BmKb2 gene also contains an intron that interrupts the exon that encodes the NDBP signal peptide. The amino acid sequences deduced for BmKb2 and BmKb1' differ only at one position. The data suggest that the genomic organizational pattern of NDBPs displays more divergence than that exhibited by the genes that encode disulfide-bridged peptides from scorpions.

Amino Acid Sequence↗
PubMed2005

Improved therapeutic effectiveness by combining recombinant CXC chemokine ligand 10 with Cisplatin in solid tumors.

PURPOSE: CXC chemokine ligand 10 (CXCL10) is a potent inhibitor of angiogenesis. We wonder whether the combination of CXCL10 with cisplatin would improve the therapeutic antitumor efficacy. EXPERIMENT DESIGN: We evaluated the antitumor activity of the combination therapy in the immunocompetent C57BL/6 and BALB/c mice bearing LL/2 Lewis lung cancer and CT26 colon adenocarcinoma, respectively. Mice were treated with either CXCL10 s.c. at 25 mug per kg per day once daily for 30 days, cisplatin cycled twice (5 mg/kg i.p. on days 14 and 21 after the initiation of CXCL10), or both agents together. Tumor volume and survival time were observed. Antiangiogenesis of CXCL10 in vivo were determined by alginate capsule models and CD31 immunohistochemistry. Histologic analysis and assessment of apoptotic cells were also conducted in tumor tissues. RESULTS: CXCL10 + cisplatin reduced tumor growth in LL/2 and CT26 tumor model, respectively, more effectively, although cisplatin or CXCL10 individually resulted in suppression of tumor growth and improved survival time of tumor-bearing mice. CXCL10 successfully inhibited angiogenesis as assessed by alginate model and CD31 (P < 0.05). Histologic analysis of tumors exhibited that CXCL10 in combination with cisplatin led to the increased rate of apoptosis, tumor necrosis, and elevated lymphocyte infiltration. CONCLUSIONS: Our data suggest that the combination of CXCL10, a well-tolerated angiogenesis inhibitor, with cisplatin can enhance the antitumor activity. The present findings may be of importance to the further exploration of the potential application of this combined approach in the treatment of lung and colon carcinoma.

Animals↗
PubMed2005

Selective synthesis of monazite- and zircon-type LaVO(4) nanocrystals.

Pure monoclinic (m-) and tetragonal phased (t-) LaVO(4) nanocrystals could be obtained by a hydrothermal method in a controllable way with additives. It is found that chelating ligands, such as ethylenediaminetetraacetic acid [EDTA or H(4)L, where L(4-) = (CH(2)COO)(2)N(CH(2))(2)N(CH(2)COO)(2)(4-)], favor the formation of t-LaVO(4) and can induce the polymorph transformation from stable m-LaVO(4) to metastable t-LaVO(4). Further studies demonstrated the important roles of chelating ligands in this transformation process. Careful investigation over the phase transition from t- to m-LaVO(4) was also conducted with high-temperature X-ray diffraction (HTXRD) studies. The phase transition occurred at 850 degrees C, which is about 250 degrees C higher than for the bulk. The enhanced thermal stability of the nanosized metastable t-LaVO(4) may come from the small size effect. Our capability of obtaining and stabilizing t-LaVO(4) not only benefits the wider applications based on LaVO(4) due to the improved luminescent and catalytic performance but also provides a new idea in the studies of polymorph control and selective synthesis of inorganic materials.

Journal Article↗
PubMed2005

Sonographic demonstration of the normal thoracic esophagus.

PURPOSE: Although conventional sonography has been used widely in evaluation of the abdominal and cervical esophagus, its use in the thoracic esophagus is seldom mentioned. The aim of this study was to assess whether conventional sonography could demonstrate the thoracic esophagus and to determine this structure's normal sonographic appearance and measurements. METHODS: Transthoracic sonography was performed in 253 healthy volunteers ranging in age from 12 to 72 years (mean, 41 +/- 15 years). The subjects were examined while supine with their hands raised over their heads; the transducer was placed along the left side of the sternum sequentially from the first to the fifth intercostal spaces. The ultrasound beam was directed to the thoracic aorta using the heart as an acoustic window. The detectable length of the thoracic esophagus was measured in the longitudinal scan from the upper most part visualized to the point at which it penetrated the diaphragm. The esophageal thickness was measured on the anterior wall at the level of the left atrium. RESULTS: In 188 (74%) of the 253 subjects, the thoracic esophagus could be demonstrated by sonography, except for the portion under the first and second intercostal spaces. In 3 of these 188 subjects, the esophagus also was not visualized at the third intercostal space. In these 188 subjects, the esophageal wall was shown as 3 layers. The esophageal lumen appeared as 1 or 2 hyperechoic bands in longitudinal sonograms. In 163 subjects, gas artifact and the comet-tail sign, with downward movement, were seen in the esophageal lumen after swallowing. The mean demonstrable length of the thoracic esophagus was 10.2 +/- 1.9 cm and the mean thickness 3.2 +/- 0.3 mm. CONCLUSIONS: Most of the thoracic esophagus can be visualized by sonography, except for a short portion at the back of the left main bronchus. The heart and the thoracic aorta are 2 important landmarks in scanning.

Adolescent↗
PubMed2005

Adaptive evolution after gene duplication in alpha-KT x 14 subfamily from Buthus martensii Karsch.

A series of isoforms of alpha-KT x 14 (short chain potassium channel scorpion toxins) were isolated from the venom of Buthus martensii Karsch by RACE and screening cDNA library methods. These isoforms adding BmKK1--3 and BmSKTx1--2 together shared high homology (more than 97%) with each other. The result of genomic sequence analysis showed that a length 79 bp intron is inserted Ala codes between the first and the second base at the 17th amino acid of signal peptide. The introns of these isoforms also share high homology with those of BmKK2 and BmSKT x 1 reported previously. Sequence analysis of many clones of cDNA and genomic DNA showed that a species population or individual polymorphism of alpha-KT x 14 genes took place in scorpion Buthus martensii Karsch and accelerated evolution played an important role in the forming process of alpha-KT x 14 scorpion toxins subfamily. The result of southern hybridization indicated that alpha-KT x 14 toxin genes existed in scorpion chromosome with multicopies. All findings maybe provided an important evidence for an extensive evolutionary process of the scorpion "pharmacological factory": at the early course of evolution, the ancestor toxic gene duplicated into a series of multicopy genes integrated at the different chromosome; at the late course of evolution, subsequent functional divergence of duplicate genes was generated by mutations, deletions and insertion.

Adaptation, Physiological↗
PubMed2005

Evolution of transcription regulatory genes is linked to niche specialization in the bacterial pathogen Streptococcus pyogenes.

Streptococcus pyogenes is a highly prevalent bacterial pathogen, most often giving rise to superficial infections at the throat or skin of its human host. Three genotype-defined subpopulations of strains exhibiting strong tropisms for either the throat or skin (specialists) or having no obvious tissue site preference (generalists) are recognized. Since the microenvironments at the throat and skin are distinct, the signal transduction pathways leading to the control of gene expression may also differ for throat versus skin strains of S. pyogenes. Two loci (mga and rofA/nra) encoding global regulators of virulence gene expression are positioned 300 kb apart on the genome; each contains alleles forming two major sequence clusters of approximately 25 to 30% divergence that are under balancing selection. Strong linkage disequilibrium is observed between sequence clusters of the transcription regulatory loci and the subpopulations of throat and skin specialists, against a background of high recombination rates among housekeeping genes. A taxonomically distinct commensal species (Streptococcus dysgalactiae subspecies equisimilus) shares highly homologous rof alleles. The findings provide strong support for a mechanism underlying niche specialization that involves orthologous replacement of regulatory genes following interspecies horizontal transfer, although the directionality of gene exchange remains unknown.

Bacterial Proteins↗