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Y Shen

Publications and source records attributed to Y Shen.

At least 91 records · Page 5Linked to original sources
PubMed2001

Isotopic evidence for microbial sulphate reduction in the early Archaean era.

Sulphate-reducing microbes affect the modern sulphur cycle, and may be quite ancient, though when they evolved is uncertain. These organisms produce sulphide while oxidizing organic matter or hydrogen with sulphate. At sulphate concentrations greater than 1 mM, the sulphides are isotopically fractionated (depleted in 34S) by 10-40/1000 compared to the sulphate, with fractionations decreasing to near 0/1000 at lower concentrations. The isotope record of sedimentary sulphides shows large fractionations relative to seawater sulphate by 2.7 Gyr ago, indicating microbial sulphate reduction. In older rocks, however, much smaller fractionations are of equivocal origin, possibly biogenic but also possibly volcanogenic. Here we report microscopic sulphides in approximately 3.47-Gyr-old barites from North Pole, Australia, with maximum fractionations of 21.1/1000, about a mean of 11.6/1000, clearly indicating microbial sulphate reduction. Our results extend the geological record of microbial sulphate reduction back more than 750 million years, and represent direct evidence of an early specific metabolic pathway--allowing time calibration of a deep node on the tree of life.

Archaea↗
PubMed2001

Constitutively activated Stat3 protects fibroblasts from serum withdrawal and UV-induced apoptosis and antagonizes the proapoptotic effects of activated Stat1.

Stats1 and 3 (signal transducers and activators of transcription) can be activated simultaneously, although not necessarily to the same degree or duration, by the interaction of cells with the same polypeptide ligand (EGF, PDGF, or high concentrations of IL-6, for example). However, these two Stat proteins can mediate opposing effects on cell growth and survival. Stat1 activation slows growth and promotes apoptosis. In contrast, activated Stat3 can protect cells from apoptosis. Furthermore, a constitutively active form of Stat3, Stat3-C (bridged by S-S linkages between cysteines instead of phosphotyrosines) can induce cellular transformation of fibroblasts. We have determined that fibroblasts transformed by Stat3-C are more resistant to proapoptotic stimuli than nontransformed cells. Also, to examine the potential opposing roles in apoptosis of Stat1 and Stat3, we studied the cervical carcinoma-derived cell line, Me180, which undergoes Stat1-dependent, IFN gamma-induced apoptosis. Me180 cells that express Stat3-C are protected against IFN gamma-mediated apoptosis.

3T3 Cells↗
PubMed2001

Rapid quantitative measurements of proteomes by Fourier transform ion cyclotron resonance mass spectrometry.

The patterns of gene expression, post-translational modifications, protein/biomolecular interactions, and how these may be affected by changes in the environment, cannot be accurately predicted from DNA sequences. Approaches for proteome characterization are generally based upon mass spectrometric analysis of in-gel digested two dimensional polyacrylamide gel electrophoresis (2-D PAGE) separated proteins, allowing relatively rapid protein identification compared to conventional approaches. This technique, however, is constrained by the speed of the 2-D PAGE separations, the sensitivity limits intrinsic to staining necessary for protein visualization, the speed and sensitivity of subsequent mass spectrometric analyses for identification, and the limited ability for accurate quantitative measurements based on differences in spot intensity. We are presently developing alternative approaches for proteomics based upon the combination of fast capillary electrophoresis, or other suitable chromatographic separations, and the high mass accuracy and sensitivity obtainable with unique Fourier transform ion cyclotron resonance (FTICR) mass spectrometers available at our laboratory. Several approaches are presently being pursued; one based upon the analysis of intact proteins and the second upon approaches for global protein digestion and accurate peptide mass analysis. Quantitation of protein/peptide levels are based on using two or more stable-isotope labeled versions of proteomes which are combined to obtain precise quantitation of relative protein abundances. We describe the status of our efforts towards the development of a high-throughput proteomics capability and present initial results for application to several microorganisms and discuss our efforts for extending the developed capability to mammalian proteomes.

Bacterial Proteins↗
PubMed2001

Inflammatory repertoire of Alzheimer's disease and nondemented elderly microglia in vitro.

We have previously developed and characterized isolated microglia and astrocyte cultures from rapid (<4 h) brain autopsies of Alzheimer's disease (AD) and nondemented elderly control (ND) patients. In the present study, we evaluate the inflammatory repertoire of AD and ND microglia cultured from white matter (corpus callosum) and gray matter (superior frontal gyrus) with respect to three major proinflammatory cytokines, three chemokines, a classical pathway complement component, a scavenger cell growth factor, and a reactive nitrogen intermediate. Significant, dose-dependent increases in the production of pro-interleukin-1beta (pro-IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory peptide-1alpha (MIP-1alpha), IL-8, and macrophage colony-stimulating factor (M-CSF) were observed after exposure to pre-aggregated amyloid beta peptide (1-42) (Abeta1-42). Across constitutive and Abeta-stimulated conditions, secretion of complement component C1q, a reactive nitrogen intermediate, and M-CSF was significantly higher in AD compared with ND microglia. Taken together with previous in situ hybridization findings, these results demonstrate unequivocally that elderly human microglia provide a brain endogenous source for a wide range of inflammatory mediators.

Aged↗
PubMed2001

Failure to express GAP-43 during neurogenesis affects cell cycle regulation and differentiation of neural precursors and stimulates apoptosis of neurons.

GAP-43 is first expressed in proliferating neuroblasts and is required for maturation of neurons. When GAP-43 is not expressed in differentiating embryonal carcinoma P19 cells, reduced numbers of neurons were generated. Here we show that neuronal differentiation is initially disrupted at the onset of cell-cycle arrest in aggregated, proliferating neuronal precursors. The ratio of nestin:beta-tubulin-labeled progeny generated at this stage suggests that the differentiation is asymmetric. Apoptosis of immature neurons subsequently produced was also significantly induced. In vivo, too, proliferation of neuroblasts was significantly reduced in cortex of GAP-43(-/-) mice at E14.5. These data demonstrate that when GAP-43 is not expressed in proliferating neuroblasts, neural differentiation is not initiated appropriately, inducing apoptosis. Moreover, the concurrent inhibition of Ca2+-dependent adhesion between differentiating P19 cells in aggregates implicates GAP-43 in CAM-mediated signaling during neurogenesis, as has been previously shown in growth cones.

Animals↗
PubMed2001

Analysis of nuclear apoptotic process in a cell-free system.

We report an analysis of the apoptotic process of mouse liver nuclei induced in a cell-free carrot cytosol system by cytochrome c. Typical characteristics of apoptosis were observed, such as chromatin condensation, margination, apoptotic bodies and DNA ladders. Furthermore, transmission and scanning electron microscope analysis of the apoptotic nuclei detected chromatin-free nuclear vesicles before apoptotic bodies appeared at a comparatively late phase. When AC-YVAD-CHO, an inhibitor of caspase 6, was introduced into the system, these vesicles and apoptotic bodies disappeared completely within our study sections. We confirmed the results using whole-mount electron microscopy, and found that although the nuclear lamina was destroyed early, the nuclear matrix largely remained intact during the course of apoptosis. The nuclear matrix played an important role in maintaining the integrity of apoptotic cells and connecting the apoptotic bodies and apoptotic nucleus.

Animals↗
PubMed2001

ASH2L: alternative splicing and downregulation during induced megakaryocytic differentiation of multipotential leukemia cell lines.

Abstract Drosophila ash2 is a member of the trxG gene super family, some human homologues of which are involved in hematopoiesis and leukemia. We report here the identification of the human homologue of Drosophila ash2 and its alternative splicing isoform, ASH2L1 and ASH2L2. ASH2L proteins are 60% homologous to Drosophila ash2. ASH2L also has a zinc finger motif (C2C2) although it is not identical to that in ASH2. Expression profile analysis showed that the amount of ASH2L transcripts is extremely high in fetal liver, testis, and leukemia cell lines with erythroid and megakaryocytic potential such as K562, Hel, and Dami. We treated these cells with differentiation inducers phorbol ester and hemin. We found that ASH2L is downregulated rapidly and dramatically in K562, Hel, and Dami cells during phorbol ester induced differentiation with megakaryocytic features. However, its expression is maintained at a high level during erythroid differentiation of K562 cells induced with hemin. These results suggest that ASH2L plays a role in hematopoiesis and is associated with some special kinds of leukemia.

Alternative Splicing↗
PubMed2001

A polymorphism in the promoter region of catalase is associated with blood pressure levels.

Catalase is an important antioxidant enzyme that detoxifies H2O2 into oxygen and water and thus limits the deleterious effects of reactive oxygen species (ROS). Because chronic exposure to excess ROS may contribute to vascular damage, we investigated whether genetic variation in catalase was associated with susceptibility to essential hypertension (EHYT) in 324 individuals (at least 50 years old) who were randomly sampled from an isolated population living in Xiangchang, China. They were screened for genetic variation in the promoter of catalase by direct sequencing. In total, four single nucleotide polymorphisms (SNPs) were identified. The association between the SNPs and EHYT was investigated by a linear regression model under phenotypic selection; in our analyses, we used both SBP>150 mmHg and SBP>160 mmHg as thresholds. A SNP 844 bp upstream of the start codon (SNP-844) demonstrated strong evidence of association with EHYT (SBP>150 mmHg: F=5.09, P=0.008; SBP>160 mmHg: F=7.13, P=0.002). This is the first study to implicate genetic variation in catalase in susceptibility to EHYT and suggests that polymorphisms in promoter regions may be particularly relevant to the study of complex diseases.

Aged↗
PubMed2001

The novel function of a short region K253xRxxxD259 conserved in the exonuclease domain of hyperthermostable DNA polymerase I from Pyrococcus horikoshii.

The DNA polymerase gene of the hyperthermophile Pyrococcus horikoshii was successfully overexpressed after removing an intein. The importance of an amino acid sequence around a highly conserved Asp was studied by site-directed mutagenesis. The results indicated that Lys253, Arg255, and Asp259 form a novel functional motif, K253xRxxxD259 (outside known motifs Exo I, II, and III), that is important not only for exonuclease activity but also for polymerizing activity, confirming functional interdependence between the polymerase and exonuclease domains. The short loop region, K253G254R255, probably contributes to binding to DNA substrates. Moreover, the negative charge and the side-chain length of D259 might play a supporting role in coordinating the conserved Mg2+ to the correct position at the active center in the exonuclease domain.

Amino Acid Sequence↗
PubMed2001

A semiflexible polymer model applied to loop formation in DNA hairpins.

A statistical mechanical "zipper" model is applied to describe the equilibrium melting of short DNA hairpins with poly(dT) loops ranging from 4 to 12 bases in the loop. The free energy of loop formation is expressed in terms of the persistence length of the chain. This method provides a new measurement of the persistence length of single-stranded DNA, which is found to be approximately 1.4 nm for poly(dT) strands in 100 mM NaCl. The free energy of the hairpin relative to the random coil state is found to scale with the loop size with an apparent exponent of > or = 7, much larger than the exponent of approximately 1.5-1.8 expected from considerations of loop entropy alone. This result indicates a strong dependence of the excess stability of the hairpins, from stacking interactions of the bases within the loop, on the size of the loop. We interpret this excess stability as arising from favorable hydrophobic interactions among the bases in tight loops and which diminish as the loops get larger. Free energy profiles along a generalized reaction coordinate are calculated from the equilibrium zipper model. The transition state for hairpin formation is identified as an ensemble of looped conformations with one basepair closing the loop, and with a lower enthalpy than the random coil state. The equilibrium model predicts apparent activation energy of approximately -11 kcal/mol for the hairpin closing step, in remarkable agreement with the value obtained from kinetics measurements.

Base Composition↗
PubMed2001

p53-dependent apoptosis pathways.

The p53 tumor suppressor limits cellular proliferation by inducing cell cycle arrest and apoptosis in response to cellular stresses such as DNA damage, hypoxia, and oncogene activation. Many apoptosis-related genes that are transcriptionally regulated by p53 have been identified. These are candidates for implementing p53 effector functions. In response to oncogene activation, p53 mediates apoptosis through a linear pathway involving bax transactivation, Bax translocation from the cytosol to membranes, cytochrome c release from mitochondria, and caspase-9 activation, followed by the activation of caspase-3, -6, and -7. p53-mediated apoptosis can be blocked at multiple death checkpoints, by inhibiting p53 activity directly, by Bcl-2 family members regulating mitochondrial function, by E1B 19K blocking caspase-9 activation, and by caspase inhibitors. Understanding the mechanisms by which p53 induces apoptosis, and the reasons why cell death is bypassed in transformed cells, is of fundamental importance in cancer research, and has great implications in the design of anticancer therapeutics.

Apoptosis↗
PubMed2001

Simultaneous quantitative UV spectrophotometric determination of multicomponents of amino acids using linear neural network.

Simultaneous determination of multicomponents of six amino acids with a novel chemometric technique-a linear neural network (LNN) algorithm is reported in this study. Based on the data correlation coefficient and standard deviation method, 17 representative wavelength points are selected from the original UV spectral data (343 points) as the original input patterns for LNN to build a neural network model. The results obtained only by iterating 15 times is satisfying, with a correlation coefficient of 0.999 and a relative small standard deviation.

Algorithms↗
PubMed2001

Simulation of biomass gasification with a hybrid neural network model.

Gasification of several types of biomass has been conducted in a fluidized bed gasifier at atmospheric pressure with steam as the fluidizing medium. In order to obtain the gasification profiles for each type of biomass, an artificial neural network model has been developed to simulate this gasification processes. Model-predicted gas production rates in this biomass gasification processes were consistent with the experimental data. Therefore, the gasification profiles generated by neural networks are considered to have properly reflected the real gasification process of a biomass. Gasification profiles identified by neural network suggest that gasification behavior of arboreal types of biomass is significantly different from that of herbaceous ones.

Biomass↗
PubMed2001

Distinct types of T-cell help for the induction of a humoral immune response to Streptococcus pneumoniae.

Studies have indicated that purified soluble polysaccharide antigens can elicit T cell-independent Ig responses in vivo, although these responses can be modulated by T cells in a noncognate manner. Relatively little is known, however, concerning the parameters that regulate polysaccharide-specific, as well as protein-specific, Ig isotype responses to an intact extracellular bacterium. Using the murine in vivo humoral response to intact Streptococcus pneumoniae as a model it can be shown that CD4+ T-cell receptor alphabeta+ T cells deliver help for both polysaccharide- and protein-specific Ig responses. However, these responses differ fundamentally in their mechanism of action.

Animals↗
PubMed2001

DSPP mutation in dentinogenesis imperfecta Shields type II.

We identified a nonsense mutation (Gln45stop) in exon 3 of the dentin sialophosphoprotein (DSPP) gene in a Chinese family with dentinogenesis imperfecta Shields type II (DGI-II), in which the affected members showed discoloration and severe attrition of their teeth, with obliterated pulp chambers.

Asian People↗
PubMed2001

Studies on the clinical efficacy and pharmacokinetics of low-dose arsenic trioxide in the treatment of relapsed acute promyelocytic leukemia: a comparison with conventional dosage.

Twenty cases of patients with relapsed acute promyelocytic leukemia (APL) were entered into this study for evaluating the clinical efficacy and pharmacokinetics of low-dose arsenic trioxide (As2O3). As2O3 was given at a daily dose of 0.08 mg/kg intravenously for 28 days. Pharmacokinetic study was carried out in eight patients. 16/20 (80%) patients achieved CR. The occurrence of some toxic events including gastrointestinal disturbance, facial edema and cardiac toxicity seemed reduced in the low-dose group than those in the standard-dose group. Differentiation changes were observed in peripheral blood, as well as in bone marrow (BM). Pharmacokinetic study showed that the plasma concentration increased soon after administration of As2O3 with the peak values of 1.535-3.424 micromol/l. After infusion, the plasma concentration was around 0.1-0.5 micromol/l. The arsenic concentration of the plasma of BM aspirates 24 h after administration in five patients was close to the level needed for differentiation-inducing effect. The estimated 2-year OS and RFS were 61.55+/-15.79% and 49.11+/-15.09% respectively, with no difference as compared with those in patients treated with conventional dose (P = 0.2865 and 0.7146, respectively). In conclusion, we demonstrated that low-dose As2O3 had the same effect as the conventional dosage and the mechanism of low-dose arsenic seemed to primarily induce differentiation of APL cells.

Adolescent↗
PubMed2001

Transient Bax-protein immunoreactivity prior to apoptosis of spiral ganglion neurons in the postnatal rat.

The apoptosis occurring in the postnatal developing spiral ganglion cells (SGCs) and the concomitant change in Bax-protein immunoreactivity were investigated in rats at postnatal days (P) 1, 3, 5, 7, 10 and 14, and also in adult rats. In P5 and P7 rats, some neurons showed structural features of apoptosis, including cell shrinkage, condensed chromatin around the margin of the nucleus and phagocytosis of apoptotic bodies by satellite cells. The percentage of Bax-protein-positive neurons in the spiral ganglion was significantly higher in P1, P3, P5, and P7 rats compared with adult rats. Our results confirm the occurrence of neuronal cell apoptosis in the spiral ganglion at the end of the first postnatal week, and demonstrate the transient change in Bax-protein immunoreactivity prior to neuronal cell apoptosis. Thus, we speculate that the transient change in Bax protein could be involved in neuronal cell apoptosis of the postnatal developing SGCs of rats.

Animals↗