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Biomedical subjects

Wen Tang

Publications and source records attributed to Wen Tang.

15 recordsLinked to original sources

Statistical inference of chromosomal homology based on gene colinearity and applications to Arabidopsis and rice.

BACKGROUND: The identification of chromosomal homology will shed light on such mysteries of genome evolution as DNA duplication, rearrangement and loss. Several approaches have been developed to detect chromosomal homology based on gene synteny or colinearity. However, the previously reported implementations lack statistical inferences which are essential to reveal actual homologies. RESULTS: In this study, we present a statistical approach to detect homologous chromosomal segments based on gene colinearity. We implement this approach in a software package ColinearScan to detect putative colinear regions using a dynamic programming algorithm. Statistical models are proposed to estimate proper parameter values and evaluate the significance of putative homologous regions. Statistical inference, high computational efficiency and flexibility of input data type are three key features of our approach. CONCLUSION: We apply ColinearScan to the Arabidopsis and rice genomes to detect duplicated regions within each species and homologous fragments between these two species. We find many more homologous chromosomal segments in the rice genome than previously reported. We also find many small colinear segments between rice and Arabidopsis genomes.

Algorithms↗

Ganoderic acid T from Ganoderma lucidum mycelia induces mitochondria mediated apoptosis in lung cancer cells.

Ganoderma lucidum is a well-known traditional Chinese medicinal herb containing many bioactive compounds. Ganoderic acid T (GA-T), which is a lanostane triterpenoid purified from methanol extract of G. lucidum mycelia, was found to exert cytotoxicity on various human carcinoma cell lines in a dose-dependent manner, while it was less toxic to normal human cell lines. Animal experiments in vivo also showed that GA-T suppressed the growth of human solid tumor in athymic mice. It markedly inhibited the proliferation of a highly metastatic lung cancer cell line (95-D) by apoptosis induction and cell cycle arrest at G(1) phase. Moreover, reduction of mitochondria membrane potential (Delta psi(m)) and release of cytochrome c were observed during the induced apoptosis. Our data further indicate that the expression of proteins p53 and Bax in 95-D cells was increased in a time-dependent manner, whereas the expression of Bcl-2 was not significantly changed; thus the ratio of Bcl-2/Bax was decreased. The results show that the apoptosis induction of GA-T was mediated by mitochondrial dysfunctions. Furthermore, stimulation of the activity of caspase-3 but not caspase-8 was observed during apoptosis. The experiments using inhibitors of caspases (Z-VAD-FMK, Z-DEVD-FMK and Z-IETD-FMK) confirmed that caspase-3 was involved in the apoptosis. All our findings demonstrate that GA-T induced apoptosis of metastatic lung tumor cells through intrinsic pathway related to mitochondrial dysfunction and p53 expression, and it may be a potentially useful chemotherapeutic agent.

Animals↗

Residual renal function and volume control in peritoneal dialysis patients.

BACKGROUND: Fluid overload is not uncommon in patients on continuous ambulatory peritoneal dialysis (CAPD). Previous studies suggested that residual renal function (RRF) played an important role in maintaining fluid balance. However, good fluid status should be a balance between fluid intake and removal. Therefore, in the present study, we investigated the effect of RRF on patients' fluid status after focusing on the balance between fluid intake and removal in CAPD patients. METHODS: In this cross-sectional study, 195 stable CAPD patients in a single center were included. Patients were divided into three groups according to their urine output: anuric group with urine < or =100 ml/day, oliguric group with urine < or =400 ml/day and UO >400 ml group with urine >400 ml/day. Fluid status was evaluated by bioimpedance analysis and mean arterial pressure (MAP). The sodium removal and plasma sodium concentration were also measured. All the patients were educated to try to achieve good volume control by focusing on salt and fluid intake and their removals. RESULTS: There were 51, 31 and 113 patients in anuric, oliguric and UO >400 ml group, respectively. Anuric patients were older and had been on CAPD longer than that of the oliguric and UO >400 ml patients (p < 0.05). The urine output in the three groups were 9.28 +/- 22.68, 236.13 +/- 75.43 and 1,013.34 +/- 541.54 ml/day, respectively (p < 0.001). Bioimpedance analysis showed that the differences of extracellular water, intracellular water and total body water were not statistically significant among the three groups. However, there was significant difference in MAP among the three groups (MAP in anuric, oliguric and UO >400 ml groups were 93.27 +/- 13.35, 96.63 +/- 9.94 and 102.36 +/- 13.70 mm Hg, p < 0.01), and UO >400 ml group had higher MAP than anuric and oliguric groups (p < 0.05). The total sodium removal (renal + peritoneal) in anuric, oliguric and UO >400 ml groups were 96.44 +/- 60.18, 98.95 +/- 73.82 and 134.64 +/- 72.44 mmol/day, respectively (p < 0.01). The UO >400 ml group also had higher plasma sodium concentration than anuric and oliguric groups (plasma sodium in the three groups were 137.49 +/- 3.43, 137.82 +/- 2.63 and 139.15 +/- 3.30 mmol/l, respectively; p < 0.01). CONCLUSIONS: This study showed that extracellular water among anuric, oliguric and UO >400 ml groups was not significantly different, which suggested that RRF may be not so important as expected in maintaining good volume status. The higher blood pressure in patients with higher RRF and higher sodium and fluid removal in the present study suggested restricting salt and fluid intake might be more important for better blood pressure control in CAPD patients.

Antihypertensive Agents↗

Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D.

The regulation of the phosphaturic factor fibroblast growth factor 23 (FGF23) is not well understood. It was found that administration of 1,25-dihydroxyvitamin D(3) (1,25[OH](2)D(3)) to mice rapidly increased serum FGF23 concentrations from a basal level of 90.6 +/- 8.1 to 213.8 +/- 14.6 pg/ml at 8 h (mean +/- SEM; P < 0.01) and resulted in a four-fold increase in FGF23 transcripts in bone, the predominate site of FGF23 expression. In the Hyp-mouse homologue of X-linked hypophosphatemic rickets, administration of 1,25(OH)(2)D(3) further increased circulating FGF23 levels. In Gcm2 null mice, low 1,25(OH)(2)D(3) levels were associated with a three-fold reduction in FGF23 levels that were increased by administration of 1,25(OH)(2)D(3). In osteoblast cell cultures, 1,25(OH)(2)D(3) but not calcium, phosphate, or parathyroid hormone stimulated FGF23 mRNA levels and resulted in a dose-dependent increase in FGF23 promoter activity. Overexpression of a dominant negative vitamin D receptor inhibited 1,25(OH)(2)D(3) stimulation of FGF23 promoter activity, and mutagenesis of the FGF23 promoter identified a vitamin D-responsive element (-1180 GGAACTcagTAACCT -1156) that is responsible for the vitamin D effects. These data suggest that 1,25(OH)(2)D(3) is an important regulator of FGF23 production by osteoblasts in bone. The physiologic role of FGF23 may be to act as a counterregulatory phosphaturic hormone to maintain phosphate homeostasis in response to vitamin D.

Animals↗

DRTF: a database of rice transcription factors.

SUMMARY: DRTF contains 2025 putative transcription factors (TFs) in Oryza sativa L. ssp. indica and 2384 in ssp. japonica, distributed in 63 families, identified by computational prediction and manual curation. It includes detailed annotations of each TF including sequence features, functional domains, Gene Ontology assignment, chromosomal localization, EST and microarray expression information, as well as multiple sequence alignment of the DNA-binding domains for each TF family. The database can be browsed and searched with a user-friendly web interface. AVAILABILITY: DRTF is available at http://drtf.cbi.pku.edu.cn

Database Management Systems↗

Nucleotide substitution pattern in rice paralogues: implication for negative correlation between the synonymous substitution rate and codon usage bias.

Understanding the correlation between synonymous substitution rate and GC content is essential to decipher the gene evolution. However, it has been controversial on their relationship. We analyzed the GC content and synonymous substitution rate in 1092 paralogues produced by two large-scale duplication events in the rice genome. According to the GC content at the third codon sites (GC3), the paralogues were classified into GC3-rich and GC3-poor genes. By referring to their outgroup sequences, we inferred the last common ancestor of sister paralogues and, consequently, calculated the average synonymous substitution rate for two gene classes. The results suggest that average synonymous substitution rate is lower in GC3-rich genes than that in GC3-poor genes, indicating that the synonymous substitution rate is negatively correlated with GC content in the rice genome. Through characterizing the synonymous nucleotide substitution pattern, we found a strong synonymous nucleotide substitution frequency bias from AT to GC in GC3-rich genes. This indicates possible limitations of commonly used methods developed to estimate the synonymous substitution rate. Their estimates might produce misleading results on correlation between the synonymous substitution rate and GC content.

Base Composition↗

Pathogenic role of Fgf23 in Hyp mice.

Inactivating mutations of the PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) endopeptidase, the disease-causing gene in X-linked hypophosphatemia (XLH), results in increased circulating levels of fibroblastic growth factor-23 (FGF23), a bone-derived phosphaturic factor. To determine the causal role of FGF23 in XLH, we generated a combined Fgf23-deficient enhanced green fluorescent protein (eGFP) reporter and Phex-deficient Hyp mouse model (Fgf23(+/-)/Hyp). eGFP expression was expressed in osteocytes embedded in bone that exhibited marked upregulation of eGFP in response to Phex deficiency and in CD31-positive cells in bone marrow venules that expressed low eGFP levels independently of Phex. In bone marrow stromal cells (BMSCs) derived from Fgf23(-/-)/Hyp mice, eGFP expression was also selectively increased in osteocyte-like cells within mineralization nodules and detected in low levels in CD31-positive cells. Surprisingly, eGFP expression was not increased in cell surface osteoblasts, indicating that Phex deficiency is necessary but not sufficient for increased Fgf23 expression in the osteoblast lineage. Additional factors, associated with either osteocyte differentiation and/or extracellular matrix, are necessary for Phex deficiency to stimulate Fgf23 gene transcription in bone. Regardless, the deletion of Fgf23 from Hyp mice reversed the hypophosphatemia, abnormal 1,25(OH)(2)D(3) levels, rickets, and osteomalacia associated with Phex deficiency. These results suggest that Fgf23 acts downstream of Phex to cause both the renal and bone phenotypes in Hyp mice.

Animals↗

Screening for and genetic analysis on T-DNA-inserted mutant pool in rice.

T-DNA tagging technique has provided a powerful strategy for identifying new functional genes in plants, and the key for success is the discovery of T-DNA-inserted mutants with changed phenotype. In this study, we screened 4,416 rice T1 tagged lines generated by enhancer trap system integrated with GLL4/VP16-UAS elements from two transformed parents, ZH11 and ZH15. We found many lines showed obvious morphological mutations, including two types--fake-homozygous mutation and separating mutation. The mutation phenotype was related to 14 kinds of trait such as plant height, heading date, leaf shape, leaf color, tiller number, panicle shape, spikelet number, grain shape, disease-like mutation, male sterility, awn, and so on. Among them, plant height, heading date, leaf color and male sterility had a comparatively high mutation frequency (over 1%). The mutation frequency of plant height and leaf color had no significant change between different years or transformed parents, but the frequency of heading date and male sterility varied greatly, suggesting that environment had a great effect on the expression of latter two traits. By conducting continuously co-segregating analyses in T1 and T2 generation, we identified 3 T-DNA-inserted mutants with malformed panicle or spikelets, which would provide a base for cloning correlative functional genes. At the same time, we selected randomly 42 lines with mutation phenotype and obtained 40 flanking sequences from 39 tagged lines by plasmid rescue or TAIL-PCR, of which, 26 were vector backbone sequence, 14 had good identity to rice genome sequence. The BlastN result showed the T-DNA preferentially integrated into protein-coding region in plants.

DNA, Bacterial↗

Diabetic patients can do as well on peritoneal dialysis as nondiabetic patients.

BACKGROUND: It is not uncommon that diabetic peritoneal dialysis (PD) patients are volume overloaded and this may have contributed to the inferior outcome of diabetic patients. In the present cohort study, we compared the difference between diabetics and nondiabetics during the first year of PD after implementing strict volume control. METHODS: Seventeen diabetic and 40 nondiabetic incident PD patients were followed for 1 year. Fluid status was evaluated by bioimpedance analysis and blood pressure. Nutritional status was evaluated by subjective global nutritional assessment. RESULTS: At the initiation, compared with the nondiabetics, diabetics had a significantly higher extracelluar volume, systolic blood pressure and lower serum albumin. One year later, there were no statistical differences in these parameters between the two groups. The prevalence of malnutrition decreased in all patients, although malnutrition remained slightly higher in diabetic patients. CONCLUSIONS: Our study suggests that diabetics can do as well as nondiabetics on PD. Appropriate diabetic care, especially strict volume control, may be critical for the success of diabetic patients on PD treatment.

Adult↗

Characterization of a thermostable UvrD helicase and its participation in helicase-dependent amplification.

Helicase-dependent amplification (HDA) is an isothermal in vitro DNA amplification method based upon the coordinated actions of helicases to separate double-stranded DNA and DNA polymerases to synthesize DNA. Previously, a mesophilic form of HDA (mHDA) utilizing the Escherichia coli UvrD helicase, DNA polymerase I Klenow fragment, two accessory proteins, MutL and single-stranded DNA-binding protein (SSB), was developed (1). In an effort to improve the specificity and performance of HDA, we have cloned and purified a thermostable UvrD helicase (Tte-UvrD) and the mutL homolog (Tte-MutL) from Thermoanaerobacter tengcongensis. Characterization of the Tte-UvrD helicase shows that it is stable and active from 45 to 65 degrees C. We have found that the Tte-UvrD helicase unwinds blunt-ended DNA duplexes as well as substrates possessing 3'- or 5'-ssDNA tails. Tte-UvrD was used to develop athermophilichelicase-dependent amplification (tHDA) system to selectively amplify target sequences at 60-65 degrees C. The tHDA system is more efficient than mHDA, displaying heightened amplification sensitivity without the need for the MutL and SSB accessory proteins. Amplification independent of MutL corresponds with studies demonstrating that maximal Tte-UvrD helicase activity does not require the mutL homolog. The tHDA system allows for rapid amplification and detection of targets present in genomic DNA. The expeditious nature and simplistic design of the tHDA platform makes the technology ideal for use in diagnostic applications requiring rapid identification of organisms at the point-of-need.

Adenosine Triphosphatases↗

c-Abl tyrosine kinase regulates c-fos gene expression via phosphorylating RNA polymerase II.

c-Abl tyrosine kinase, predominantly distributed in nucleus, has been implicated in many important cellular processes including the regulation of gene transcription. In this study, we showed that c-Abl promoted the transcription of c-fos gene, both exogenously and endogenously. The nuclear localization and tyrosine kinase activity of c-Abl were required for the activation of c-fos gene. c-Abl was associated with RNA polymerase II (RNAP II) in vivo and augmented the tyrosine phosphorylation of the largest subunit of RNAP II. In addition, c-Abl and RNAP II could be recruited to the region of c-fos promoter. The combined results suggest that c-Abl plays an important role in the transcriptional regulation of c-fos gene and the tyrosine phosphorylation of the largest subunit of RNAP II by c-Abl is involved in the regulating process.

Active Transport, Cell Nucleus↗

Strong association between volume status and nutritional status in peritoneal dialysis patients.

BACKGROUND: Malnutrition is a strong predictor of mortality in maintenance peritoneal dialysis (PD) patients. Various factors have been identified to contribute to the development of malnutrition. The present study tried to investigate the possible role of fluid overload in the development of malnutrition. METHODS: Twenty-eight PD patients were included in this study. Fluid status was evaluated by means of repeated bioimpedance analysis, and nutritional status was assessed by means of handgrip strength and subjective global assessment. All patients were followed up closely for 9 months. Based on changes in bioimpedance analysis data, patients were divided into group A (with continuous and steadily improved fluid status; n = 18) and group B (with consistent fluid overload; n = 10). RESULTS: There were no differences in sex, age, and height between the 2 groups. In group A, patients' extracellular water (ECW) volume decreased significantly during follow-up, whereas intracellular water (ICW) volume increased significantly (both P < 0.001). In group B, ECW volume increased significantly, whereas ICW volume increased at an early stage and then decreased. The ratio of ECW to total-body water decreased significantly in group A, but increased significantly in group B. Along with the improvement in fluid status, nutritional status in group A also improved significantly (the prevalence of malnutrition decreased from 66.7% to 11.1%; P < 0.01). However, in group B, nutritional status deteriorated significantly (handgrip strength decreased from 238.33 +/- 88.93 to 216.1 +/- 86.19 N; P < 0.05; and the prevalence of malnutrition increased from 40% to 50%). CONCLUSION: Our data suggest there is a strong association between fluid status and nutritional status. Improved fluid status is associated with improvement in nutritional status, whereas deterioration in fluid status is associated with the development of malnutrition.

Adult↗

APOE genotype and an ApoE-mimetic peptide modify the systemic and central nervous system inflammatory response.

Human apolipoprotein E is the major apolipoprotein expressed in the brain and exists as three isoforms, designated E2, E3, and E4. Although evidence suggests that apolipoprotein E plays an important role in modifying systemic and brain inflammatory responses, there is little data investigating apoE isoform-specific effects in vivo. In this study, we compared the inflammatory responses of targeted-replacement mice expressing the human APOE3 and APOE4 genes after intravenous administration of lipopolysaccharide. Animals expressing the E4 allele had significantly greater systemic and brain elevations of the pro-inflammatory cytokines TNFalpha and IL-6 as compared with their APOE3 counterparts, suggesting an isoform-specific effect of the immunomodulatory properties of apoE. Furthermore, intravenous administration of a small apoE-mimetic peptide derived from the receptor-binding region of the apoE holoprotein (apoE-(133-149)) similarly suppressed both systemic and brain inflammatory responses in mice after lipopolysaccharide administration. These results suggest that apoE plays an isoform-specific role in mediating the systemic and brain inflammatory responses. Moreover, because exogenous administration of this apoE mimetic peptide is effective at suppressing both systemic and brain inflammation, it may represent a novel therapeutic strategy for diseases characterized by systemic or central nervous system inflammation, such as septic shock, multiple sclerosis, and traumatic brain injury.

Amino Acid Sequence↗

Human secreted attractin disrupts neurite formation in differentiating cortical neural cells in vitro.

Mutations at the Atrn locus that encodes a transmembrane protein with a large ectodomain are responsible for a juvenile-onset neurodegeneration manifest as hypomyelination and cerebral vacuole development in several rodent species. In addition to a membrane isoform, the human Atm locus generates by alternative splicing a secreted form corresponding to the entire ectodomain that then circulates at high concentration in the periphery, released in part by activated T lymphocytes. We report here that the secreted form mRNA is downregulated throughout representative discrete regions of the human brain while membrane attractin mRNA is well represented, resulting in the apparent absence of secreted attractin protein in cerebrospinal fluid (CSF). Transcription of attractin secreted form mRNA is strongly downregulated upon differentiation of a human cortical neuron-derived cell line (HCN-1A) to a mature neuron phenotype in response to nerve growth factor. Recombinant secreted attractin disrupts neurite formation by differentiated HCN-1A cells, resulting in higher levels of branching with shorter processes. This effect is duplicated by anti-attractin and by human serum but not by human serum depleted of attractin or by CSF We propose that inappropriate expression of secreted attractin in the CNS blocks membrane attractin function and that its presence, either by leakage from the periphery, aberrant transcription, or release from inflammatory foci may affect neuron extracellular interactions leading to neurodegeneration in the human.

Animals↗