Hypoxia and HIF-1alpha protect A549 cells from drug-induced apoptosis.
Explore the source record for details and available documents.
Apoptosis↗
Biomedical subjects
J Zhou
Publications and source records attributed to J Zhou.
Antitumor efficacy of AAV-mediated systemic delivery of interferon-beta.
Type I interferons (alpha/beta) have significant antitumor activity although their short half-life and systemic side effects have limited their clinical utility. An alternative dosing schedule of continuous, low-level delivery, as is achieved by gene therapy, rather than intermittent, high concentration pulsed-dosing, might avoid the toxicity of interferon while maintaining its antitumor efficacy. We have tested a gene therapy approach in murine tumor models to treat malignancies that have shown responsiveness to interferon in clinical trials. The tumor cell lines used were moderately sensitive to the direct effects of human interferon-beta (hIFN-beta) in vitro. For in vivo testing, systemic delivery of hIFN-beta was generated following liver-targeted delivery of adeno-associated virus (AAV) vector carrying the hIFN-beta transgene. This prevented engraftment of subcutaneous human gliomas, and orthotopic, localized (intrarenal) and disseminated (primarily pulmonary) human renal cell carcinomas; and caused regression of established tumors at these sites. In a syngeneic, immunocompetent model of melanoma, AAV IFN-beta treatment limited subcutaneous tumor growth and prevented disseminated disease. A significant decrease in mean intratumoral vessel density was demonstrated in hIFN-beta-treated tumors, suggesting that in addition to a direct tumoricidal effect, the antitumor efficacy of AAV IFN-beta in this study was due to its ability to inhibit angiogenesis.
Animals↗
cisRED: a database system for genome-scale computational discovery of regulatory elements.
We describe cisRED, a database for conserved regulatory elements that are identified and ranked by a genome-scale computational system (www.cisred.org). The database and high-throughput predictive pipeline are designed to address diverse target genomes in the context of rapidly evolving data resources and tools. Motifs are predicted in promoter regions using multiple discovery methods applied to sequence sets that include corresponding sequence regions from vertebrates. We estimate motif significance by applying discovery and post-processing methods to randomized sequence sets that are adaptively derived from target sequence sets, retain motifs with p-values below a threshold and identify groups of similar motifs and co-occurring motif patterns. The database offers information on atomic motifs, motif groups and patterns. It is web-accessible, and can be queried directly, downloaded or installed locally.
Animals↗
Inhibition of telomerase enhances apoptosis induced by sodium butyrate via mitochondrial pathway.
Telomerase activation represents an early step in carcinogenesis. Increased telomerase activity in cervical cancer suggests a potential target for the development of novel therapeutic drugs. The aim of this study is to investigate the impact of telomerase activity on the biological features of HeLa cells and the possible mechanisms of enhanced apoptosis rate induced by sodium butyrate after telomerase inhibition. We introduced vectors encoding dominate negative (DN)-hTERT, wild-type (WT)-hTERT, or a control vector expressing only a drug-resistance marker into HeLa cells. Thus we assessed the biological effects of telomerase activity on telomere length, cell proliferation, chemosensitivity and radiosensitivity. In order to understand the mechanisms in which DN-hTERT enhances the apoptosis induced by sodium butyrate, we detected the release status of cytochrome c and apoptosis inducing factor (AIF) from mitochondria. Ectopic expression of DN-hTERT resulted in inhibition of telomerase activity, reduction of telomere length, decreased colony formation ability, and loss of tumorigenicity in nude mice. Moreover, DN-hTERT transfected HeLa cells with shortened telomeres were more susceptible to multiple chemotherapeutic agents and radiation. WT-hTERT transfected HeLa cells with longer telomeres exhibited resistance to radiation and chemotherapeutic agents. Our data demonstrate that elevated release level of cytochrome c and AIF from mitochondria might contribute to the enhanced apoptosis in DN-hTERT transfected HeLa cells after treatment with sodium butyrate. Inhibition of telomerase might serve as a promising adjunctive therapy combined with conventional therapy in cervical cancer.
Animals↗
Inhibition of ovarian cancer metastasis by adeno-associated virus-mediated gene transfer of nm23H1 in an orthotopic implantation model.
Ovarian cancer is one of the most threatening malignant tumors in females due to the frequent occurrence of metastasis that precedes diagnosis. The present study explored the possibility of preventing ovarian cancer metastasis by promoting nm23H1 expression through adeno-associated virus (AAV)-mediated gene transfer. A cell line of high metastatic potential, SW626-M4, was derived by in vivo selection and used to establish an ovarian cancer metastasis model in the mouse. Liver metastasis and animal survival time were measured after transfer of a recombinant adeno-associated viral vector expressing nm23H1 (AAV-nm23H1) into the aforementioned model. Intraperitoneal injection of AAV-nm23H1 into this orthotopic implantation model of ovarian cancer resulted in (1) expression of the exogenous gene in more than 95% of tumor cells in situ in nude mice; (2) a 60% reduction in the number of animals developing liver metastases; and (3) a 35-day prolongation of median survival time compared with the untreated host group. In conclusion, the results support the feasibility of induction of nm23H1 expression through gene transfer as a therapeutic strategy for preventing metastases and prolonging host survival time, and indicate that AAV vectors deserve attention in the design of future gene therapy approaches to achieving long-term expression of curative genes in vivo.
Adenocarcinoma↗
Application of nano-indenter for investigation of the properties of the elytra cuticle of the dung beetle (Copris ochus Motschulsky).
The nanomechanical properties of the multilayer elytra cuticle of the dung beetle (Copris ochus Motschulsky) were investigated in the vertical and transverse directions using a nano-indenter. The reduced modulus Ev and hardness Hv of the surface cuticle in the vertical direction obtained by nano-indentation were 3.54+/-0.12 GPa and 0.20+/-0.01 GP, respectively. The nano-indentation result showed that the reduced modulus E(t) and hardness Ht of each layer were gradually reduced from the outer layer to the inner layer in the transverse direction. Ev was less than the largest Et presented at the outer layer (7.06+/-0.54 GPa). It was supposedly formed as a result of the composite effect of the multilayer. Without consideration of the anisotropy of chitin, an experimental model was proposed to describe the nanomechanical properties of the elytra cuticle.
Animals↗
A new naphthaquinone derivative from Chirita eburnea.
A new compound, methyl 3-(4'-hydroxyphenethylamino)-1,4-dihydro-1,4-dioxonaphthalene-2-carboxylate (1) was isolated from Chirita eburnea. Its structure was elucidated on the basis of 1D NMR, 2D NMR and MS analysis.
Carboxylic Acids↗
Application of I(125) brachytherapy combined artificial joint prosthesis in malignant osteo- and soft-tissue sarcoma.
OBJECTIVES: The aim of this study was to evaluate the brachytherapy effectiveness of I(125) seeds combined with artificial prosthesis in malignant sarcoma therapy. METHODS: The combination of I(125) seeds and artificial prosthesis was implanted to replace tumor section for three clinical cases-2 malignant osteosarcoma patients and 1 malignant soft-tissue tumor patient- through the direct operation. RESULTS: Approximately 14-18 months after the operation, the results of our post-operational investigation showed that the tumor tissues of 3 patients had been completely removed. The limb functions recovered well. The brachytherapy of the combination of I(125) seeds and artificial prosthesis in malignant tumor improved the curative effect. No tumor existed, and no infection occurred. CONCLUSIONS: It was demonstrated that this method was safe and easy. No side-effect was observed after the implantation of I(125) seeds. The brachytherapy was proven to be a potential method for patients who were at high risk to recrudesce the malignant osteosarcoma of tumors after the tumor excision.
Adolescent↗
Global analysis of heat shock response in Desulfovibrio vulgaris Hildenborough.
Desulfovibrio vulgaris Hildenborough belongs to a class of sulfate-reducing bacteria (SRB) and is found ubiquitously in nature. Given the importance of SRB-mediated reduction for bioremediation of metal ion contaminants, ongoing research on D. vulgaris has been in the direction of elucidating regulatory mechanisms for this organism under a variety of stress conditions. This work presents a global view of this organism's response to elevated growth temperature using whole-cell transcriptomics and proteomics tools. Transcriptional response (1.7-fold change or greater; Z >/= 1.5) ranged from 1,135 genes at 15 min to 1,463 genes at 120 min for a temperature up-shift of 13 degrees C from a growth temperature of 37 degrees C for this organism and suggested both direct and indirect modes of heat sensing. Clusters of orthologous group categories that were significantly affected included posttranslational modifications; protein turnover and chaperones (up-regulated); energy production and conversion (down-regulated), nucleotide transport, metabolism (down-regulated), and translation; ribosomal structure; and biogenesis (down-regulated). Analysis of the genome sequence revealed the presence of features of both negative and positive regulation which included the CIRCE element and promoter sequences corresponding to the alternate sigma factors sigma(32) and sigma(54). While mechanisms of heat shock control for some genes appeared to coincide with those established for Escherichia coli and Bacillus subtilis, the presence of unique control schemes for several other genes was also evident. Analysis of protein expression levels using differential in-gel electrophoresis suggested good agreement with transcriptional profiles of several heat shock proteins, including DnaK (DVU0811), HtpG (DVU2643), HtrA (DVU1468), and AhpC (DVU2247). The proteomics study also suggested the possibility of posttranslational modifications in the chaperones DnaK, AhpC, GroES (DVU1977), and GroEL (DVU1976) and also several periplasmic ABC transporters.
Bacterial Proteins↗
Fabrication and characteristics of bioactive sodium titanate/titania graded film on NiTi shape memory alloy.
A bioactive sodium titanate/titania graded film was formed in situ on NiTi shape memory alloy (SMA) by oxidizing in H(2)O(2) solution and subsequent NaOH treatment and characterized by scanning electron microscopy, Raman spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy (XPS). The bioactivity of the film was investigated using a simulated body fluid (SBF) soaking test. A titania (TiO(2)) layer was first found on NiTi substrate after oxidized in H(2)O(2) solution, and then a porous sodium titanate (Na(2)TiO(3))/titania film with many Ti--OH groups and a trace of Ni(2)O(3) was formed by the reaction of partial TiO(2) phase with NaOH solution. After immersion in SBF for 12 h, apatite was observed to nucleate and grow on the film. With longer soaking time, more apatite appeared on its surface but our control experiments didn't reveal any apatite formation on the chemically polished NiTi SMA, which indicates the bioactivity of NiTi implants could be improved by the formation of the bioactive film. Moreover, XPS depth profiles of O, Ni, Ti, and Na show the bioactive film possesses a smooth graded interface structure to NiTi substrate, which is in favor of sufficient mechanical stability of apatite layer by subsequent deposition in SBF.
Biocompatible Materials↗
Saturation of the magnetic response of split-ring resonators at optical frequencies.
We investigate numerically the limits of the resonant magnetic response with a negative effective permeability mu(eff) for single-ring multicut split-ring resonator (SRR) designs up to optical frequencies. We find the breakdown of linear scaling due to the free electron kinetic energy for frequencies above approximately 100 THz. Above the linear scaling regime, the resonance frequency saturates, while the amplitude of the resonant permeability decreases, ultimately ceasing to reach negative value. The highest resonance frequency at which mu(eff) < 0 increases with the number of cuts in the SRR. A LC circuit model provides explanation of the numerical data.
Journal Article↗
Changes in bacterial community structure correlate with initial operating conditions of a field-scale denitrifying fluidized bed reactor.
High levels of nitrate are present in groundwater migrating from the former waste disposal ponds at the Y-12 National Security Complex in Oak Ridge, TN. A field-scale denitrifying fluidized bed reactor (FBR) was designed, constructed, and operated with ethanol as an electron donor for the removal of nitrate. After inoculation, biofilms developed on the granular activated carbon particles. Changes in the bacterial community of the FBR were evaluated with clone libraries (n = 500 partial sequences) of the small-subunit rRNA gene for samples taken over a 4-month start-up period. Early phases of start-up operation were characterized by a period of selection, followed by low diversity and predominance by Azoarcus-like sequences. Possible explanations were high pH and nutrient limitations. After amelioration of these conditions, diversification increased rapidly, with the appearance of Dechloromonas, Pseudomonas, and Hydrogenophaga sequences. Changes in NO3, SO4, and pH also likely contributed to shifts in community composition. The detection of sulfate-reducing-bacteria-like sequences closely related to Desulfovibrio and Desulfuromonas in the FBR have important implications for downstream applications at the field site.
Bacteria↗
Loss of PKD1 and loss of Bcl-2 elicit polycystic kidney disease through distinct mechanisms.
We have recently demonstrated that ablation of one or both alleles of the proapoptotic gene Bim prevents the polycystic kidney disease (PKD) that develops in mice deficient for the prosurvival protein Bcl-2. The aim of the present study was to investigate whether loss of Bim or Bcl-2 could influence the disease in the PKD1del34/del34 mutant mice, a model of autosomal dominant PKD. PKD1del34/del34 mice were intercrossed with Bim-deficient mice and Bcl-2+/- mice to generate double mutants. Loss of Bim does not prevent the development of PKD in PKD1del34/del34 mice. On the C57BL/6 genetic background, most older PKD1del34/+ mice do not develop PKD, but present with liver cysts. Surprisingly, loss of Bim completely prevented liver cysts formation in PKD1del34/+ mice. Loss of one Bcl-2 allele did not influence the PKD1del34 phenotype significantly. We conclude that loss of PKD1 and loss of Bcl-2 elicit PKD through distinct mechanisms.
Animals↗
A coarse graining approach to determine nucleic acid structures from small angle neutron scattering profiles in solution.
We present a theoretical method to calculate the small angle neutron scattering profile of nucleic acid structures in solution. Our approach is sensitive to the sequence and the structure of the nucleic acid. In order to test our approach, we apply this method to the calculation of the experimental scattered intensity of the decamer d(CCAACGTTGG)2 in H2O. This sequence was specifically chosen for this study as it is believed to adopt a canonical B-form structure in 0.3 M NaCl. We find that not only will our methodology reproduce the experimental scattered intensity for this sequence, but our method will also discriminate between B-, A- and Z-form DNA. By studying the scattering profile of this structure in 0.5 and 1.0 M NaCl, we are also able to identify tetraplex and other similar oligomers formation and to model the complex using the experimental scattering data in conjunction with our methodology.
Base Sequence↗
Conformational changes in single-strand DNA as a function of temperature by SANS.
Small-angle neutron scattering (SANS) measurements were performed on a solution of single-strand DNA, 5'-ATGCTGATGC-3', in sodium phosphate buffer solution at 10 degrees C temperature increments from 25 degrees C to 80 degrees C. Cylindrical, helical, and random coil shape models were fitted to the SANS measurements at each temperature. All the shapes exhibited an expansion in the diameter direction causing a slightly shortened pitch from 25 degrees C to 43 degrees C, an expansion in the pitch direction with a slight decrease in the diameter from 43 degrees C to 53 degrees C, and finally a dramatic increase in the pitch and diameter from 53 degrees C to 80 degrees C. Differential scanning calorimeter scans of the sequence in solution exhibited a reversible two-state transition profile with a transition temperature of 47.5 +/- 0.5 degrees C, the midpoint of the conformational changes observed in the SANS measurements, and a calorimetric transition enthalpy of 60 +/- 3 kJ mol(-1) that indicates a broad transition as is observed in the SANS measurements. A transition temperature of 47 +/- 1 degrees C was also obtained from ultraviolet optical density measurements of strand melting scans of the single-strand DNA. This transition corresponds to unstacking of the bases of the sequence and is responsible for the thermodynamic discrepancy between its binding stability to its complementary sequence determined directly at ambient temperatures and determined from extrapolated values of the melting of the duplex at high temperature.
Algorithms↗
Interfacial failure of a dental cement composite bonded to glass substrates.
OBJECTIVES: To measure the interfacial fracture toughness and investigate failure mechanisms of dental cements bound to soda-lime glasses elastically equivalent to dental ceramics, as loading angle changes from 0 to 20 degrees . METHODS: Two half-circle glass discs received surface treatment were bound using dental cement (3M RelyXTM ARC BLBL) to make Brazil-nut sandwich specimens for interfacial toughness testing. Before bonding the two half-circle glass disks, 8% hydrofluoric acid (HF) was applied on the surfaces to bond for 2 min, washed thoroughly for 1 min under tap water and air dried. The surfaces were further treated using silane primer Monobond-s (Vivadent, Liechtenstein) for 60s and air dried. Interfacial toughness as a function of mode mixity was measured using an Instron testing machine by changing loading angels from 0 to 20 degrees . The interfacial fracture surfaces were examined using SEM and EDX to determine the failure modes when loading angles change. RESULTS: Interfacial toughness increases from approximately 1 to 8 J/m/m when loading angle increases from 0 to approximately 20 degrees . Increasing deformation and fracture in dental cement occur when loading angle increases. SIGNIFICANCES: Increasing interfacial toughness can be attributed to more deformation and fracture of dental cement when loading angle increases. Brazil-nut sandwich samples are shown to provide a promising alternative method to evaluate bond strength and interfacial failure for dental restoration. Research was supported by NIH (NYU/PHS No. F5262-07).
Acid Etching, Dental↗
Q2 dependence of the neutron spin structure function g2(n) at low Q2.
We present the first measurement of the Q2 dependence of the neutron spin structure function g2(n) at five kinematic points covering 0.57 (GeV/c)2 < or = Q2 < or = 1.34 (GeV/c)2 at x approximately = 0.2. Though the naive quark-parton model predicts g2 = 0, nonzero values occur in more realistic models of the nucleon which include quark-gluon correlations, finite quark masses, or orbital angular momentum. When scattering from a noninteracting quark, g2(n) can be predicted using next-to-leading order fits to world data for g1(n). Deviations from this prediction provide an opportunity to examine QCD dynamics in nucleon structure. Our results show a positive deviation from this prediction at lower Q2, indicating that contributions such as quark-gluon interactions may be important. Precision data obtained for g1(n) are consistent with next-to-leading order fits to world data.
Journal Article↗
Genome-wide expression profiling of human blood reveals biomarkers for Huntington's disease.
Huntington's disease (HD) is an autosomal dominant disorder caused by an expansion of glutamine repeats in ubiquitously distributed huntingtin protein. Recent studies have shown that mutant huntingtin interferes with the function of widely expressed transcription factors, suggesting that gene expression may be altered in a variety of tissues in HD, including peripheral blood. Affymetrix and Amersham Biosciences oligonucleotide microarrays were used to analyze global gene expression in blood samples of HD patients and matched controls. We identified 322 mRNAs that showed significantly altered expression in HD blood samples, compared with controls (P < 0.0005), on two different microarray platforms. A subset of up-regulated mRNAs selected from this group was able to distinguish controls, presymptomatic individuals carrying the HD mutation, and symptomatic HD patients. In addition, early presymptomatic subjects showed gene expression profiles similar to those of controls, whereas late presymptomatic subjects showed altered expression that resembled that of symptomatic HD patients. These elevated mRNAs were significantly reduced in HD patients involved in a dose-finding study of the histone deacetylase inhibitor sodium phenylbutyrate. Furthermore, expression of the marker genes was significantly up-regulated in postmortem HD caudate, suggesting that alterations in blood mRNAs may reflect disease mechanisms observed in HD brain. In conclusion, we identified changes in blood mRNAs that clearly distinguish HD patients from controls. These alterations in mRNA expression correlate with disease progression and response to experimental treatment. Such markers may provide clues to the state of HD and may be of predictive value in clinical trials.
Adult↗