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Sample records for chromium 53 target

  1. Delta Chromium-53/52 isotopic composition of native and contaminated groundwater, Mojave Desert, USA

    Science.gov (United States)

    Izbicki, John A.; Bullen, Thomas D.; Martin, Peter; Schroth, Brian

    2012-01-01

    Chromium(VI) concentrations in groundwater sampled from three contaminant plumes in aquifers in the Mojave Desert near Hinkley, Topock and El Mirage, California, USA, were as high as 2600, 5800 and 330 μg/L, respectively. δ53/52Cr compositions from more than 50 samples collected within these plumes ranged from near 0‰ to almost 4‰ near the plume margins. Assuming only reductive fractionation of Cr(VI) to Cr(III) within the plume, apparent fractionation factors for δ53/52Cr isotopes ranged from εapp = 0.3 to 0.4 within the Hinkley and Topock plumes, respectively, and only the El Mirage plume had a fractionation factor similar to the laboratory derived value of ε = 3.5. One possible explanation for the difference between field and laboratory fractionation factors at the Hinkley and Topock sites is localized reductive fractionation of Cr(VI) to Cr(III), with subsequent advective mixing of native and contaminated water near the plume margin. Chromium(VI) concentrations and δ53/52Cr isotopic compositions did not uniquely define the source of Cr near the plume margin, or the extent of reductive fractionation within the plume. However, Cr(VI) and δ53/52Cr data contribute to understanding of the interaction between reductive and mixing processes that occur within and near the margins of Cr contamination plumes. Reductive fractionation of Cr(VI) predominates in plumes having higher εapp, these plumes may be suitable for monitored natural attenuation. In contrast, advective mixing predominates in plumes having lower εapp, the highly dispersed margins of these plumes may be difficult to define and manage.

  2. Identification of p53-target genes in Danio rerio

    Science.gov (United States)

    Mandriani, Barbara; Castellana, Stefano; Rinaldi, Carmela; Manzoni, Marta; Venuto, Santina; Rodriguez-Aznar, Eva; Galceran, Juan; Nieto, M. Angela; Borsani, Giuseppe; Monti, Eugenio; Mazza, Tommaso; Merla, Giuseppe; Micale, Lucia

    2016-01-01

    To orchestrate the genomic response to cellular stress signals, p53 recognizes and binds to DNA containing specific and well-characterized p53-responsive elements (REs). Differences in RE sequences can strongly affect the p53 transactivation capacity and occur even between closely related species. Therefore, the identification and characterization of a species-specific p53 Binding sistes (BS) consensus sequence and of the associated target genes may help to provide new insights into the evolution of the p53 regulatory networks across different species. Although p53 functions were studied in a wide range of species, little is known about the p53-mediated transcriptional signature in Danio rerio. Here, we designed and biochemically validated a computational approach to identify novel p53 target genes in Danio rerio genome. Screening all the Danio rerio genome by pattern-matching-based analysis, we found p53 RE-like patterns proximal to 979 annotated Danio rerio genes. Prioritization analysis identified a subset of 134 candidate pattern-related genes, 31 of which have been investigated in further biochemical assays. Our study identified runx1, axin1, traf4a, hspa8, col4a5, necab2, and dnajc9 genes as novel direct p53 targets and 12 additional p53-controlled genes in Danio rerio genome. The proposed combinatorial approach resulted to be highly sensitive and robust for identifying new p53 target genes also in additional animal species. PMID:27581768

  3. Identification of p53-target genes in Danio rerio.

    Science.gov (United States)

    Mandriani, Barbara; Castellana, Stefano; Rinaldi, Carmela; Manzoni, Marta; Venuto, Santina; Rodriguez-Aznar, Eva; Galceran, Juan; Nieto, M Angela; Borsani, Giuseppe; Monti, Eugenio; Mazza, Tommaso; Merla, Giuseppe; Micale, Lucia

    2016-01-01

    To orchestrate the genomic response to cellular stress signals, p53 recognizes and binds to DNA containing specific and well-characterized p53-responsive elements (REs). Differences in RE sequences can strongly affect the p53 transactivation capacity and occur even between closely related species. Therefore, the identification and characterization of a species-specific p53 Binding sistes (BS) consensus sequence and of the associated target genes may help to provide new insights into the evolution of the p53 regulatory networks across different species. Although p53 functions were studied in a wide range of species, little is known about the p53-mediated transcriptional signature in Danio rerio. Here, we designed and biochemically validated a computational approach to identify novel p53 target genes in Danio rerio genome. Screening all the Danio rerio genome by pattern-matching-based analysis, we found p53 RE-like patterns proximal to 979 annotated Danio rerio genes. Prioritization analysis identified a subset of 134 candidate pattern-related genes, 31 of which have been investigated in further biochemical assays. Our study identified runx1, axin1, traf4a, hspa8, col4a5, necab2, and dnajc9 genes as novel direct p53 targets and 12 additional p53-controlled genes in Danio rerio genome. The proposed combinatorial approach resulted to be highly sensitive and robust for identifying new p53 target genes also in additional animal species. PMID:27581768

  4. Targeting p53 and its domains for cancer gene therapy

    OpenAIRE

    Karina Julia Matissek

    2014-01-01

    The tumor suppressor p53 is one of the most frequently mutated proteins in human cancer and has been extensively targeted for cancer therapy. This resulted in wild type p53 gene therapeutic approval for the treatment of head and neck cancer in China. p53 mainly functions as a transcription factor and stimulates a variety of genes involved in the intrinsic and extrinsic apoptotic pathway by binding to p53 responsive elements as a t...

  5. p53 as an intervention target for cancer and aging

    Directory of Open Access Journals (Sweden)

    Paul Hasty

    2013-10-01

    Full Text Available p53 is well known for suppressing tumors but could also affect other aging processes not associated with tumor suppression. As a transcription factor, p53 responds to a variety of stresses to either induce apoptosis (cell death or cell cycle arrest (cell preservation to suppress tumor development. Yet, the effect p53 has on the non-cancer aspects of aging is complicated and not well understood. On one side, p53 could induce cellular senescence or apoptosis to suppress cancer but as an unintended consequence enhance the aging process especially if these responses diminish stem and progenitor cell populations. But on the flip side, p53 could reduce growth and growth-related stress to enable cell survival and ultimately delay the aging process. A better understanding of diverse functions of p53 is essential to elucidate its influences on the aging process and the possibility of targeting p53 or p53 transcriptional targets to treat cancer and ameliorate general aging.

  6. The p53 target Wig-1 regulates p53 mRNA stability through an AU-rich element

    DEFF Research Database (Denmark)

    Vilborg, Anna; Glahder, Jacob-Andreas Harald; Wilhelm, Margareta T;

    2009-01-01

    The p53 target gene Wig-1 encodes a double-stranded-RNA-binding zinc finger protein. We show here that Wig-1 binds to p53 mRNA and stabilizes it through an AU-rich element (ARE) in the 3' UTR of the p53 mRNA. This effect is mirrored by enhanced p53 protein levels in both unstressed cells and cells...... exposed to p53-activating stress agents. Thus, the p53 target Wig-1 is a previously undescribed ARE-regulating protein that acts as a positive feedback regulator of p53, with implications both for the steady-state levels of p53 and for the p53 stress response. Our data reveal a previously undescribed link...... between the tumor suppressor p53 and posttranscriptional gene regulation via AREs in mRNA....

  7. Suicide genes or p53 gene and p53 target genes as targets for cancer gene therapy by ionizing radiation

    International Nuclear Information System (INIS)

    Radiotherapy has some disadvantages due to the severe side-effect on the normal tissues at a curative dose of ionizing radiation (IR). Similarly, as a new developing approach, gene therapy also has some disadvantages, such as lack of specificity for tumors, limited expression of therapeutic gene, potential biological risk. To certain extent, above problems would be solved by the suicide genes or p53 gene and its target genes therapies targeted by ionizing radiation. This strategy not only makes up the disadvantage from radiotherapy or gene therapy alone, but also promotes success rate on the base of lower dose. By present, there have been several vectors measuring up to be reaching clinical trials. This review focused on the development of the cancer gene therapy through suicide genes or p53 and its target genes mediated by IR. (authors)

  8. Methylation levels of P16 and TP53 that are involved in DNA strand breakage of 16HBE cells treated by hexavalent chromium.

    Science.gov (United States)

    Hu, Guiping; Li, Ping; Li, Yang; Wang, Tiancheng; Gao, Xin; Zhang, Wenxiao; Jia, Guang

    2016-05-13

    The correlations between methylation levels of p16 and TP53 with DNA strand breakage treated by hexavalent chromium [Cr(VI)] remain unknown. In this research, Human bronchial epithelial cells (16HBE cells) in vitro and bioinformatics analysis were used to analyze the epigenetic role in DNA damage and potential biomarkers. CCK-8 and single cell gel electrophoresis assay were chosen to detect the cellular biological damage. MALDI-TOF-MS was used to detect the methylation levels of p16 and TP53. qRT-PCR was used to measure their expression levels in different Cr(VI) treatment groups. The transcription factors with target sequences of p16 and TP53 were predicted using various bioinformatics software. The findings showed that the cellular toxicity and DNA strand damage were Cr(VI) concentration dependent. The hypermethylation of CpG1, CpG31 and CpG32 of p16 was observed in Cr(VI) treated groups. There was significant positive correlation between the CpG1 methylation level of p16 and cell damage. In Cr(VI) treated groups, the expression level of p16 was lower than that in control group. The expression level of TP53 increased when the Cr(VI)concentration above 5μM. About p16, there was significant negative correlation between the CpG1 methylation levels with its expression level. A lot of binding sites for transcription factors existed in our focused CpG islands of p16. All the results suggested that the CpG1 methylation level of p16 could be used as a biomarker of epigenetic effect caused by Cr(VI) treatment, which can enhance cell damage by regulating its expression or affecting some transcription factors to combine with their DNA strand sites. PMID:27005777

  9. Cancer-derived p53 mutants suppress p53-target gene expression—potential mechanism for gain of function of mutant p53

    OpenAIRE

    Vikhanskaya, Faina; Lee, Ming Kei; Mazzoletti, Marco; Broggini, Massimo; Sabapathy, Kanaga

    2007-01-01

    Tumour-derived p53 mutants are thought to have acquired ‘gain-of-function’ properties that contribute to oncogenicity. We have tested the hypothesis that p53 mutants suppress p53-target gene expression, leading to enhanced cellular growth. Silencing of mutant p53 expression in several human cell lines was found to lead to the upregulation of wild-type p53-target genes such as p21, gadd45, PERP and PTEN. The expression of these genes was also suppressed in H1299-based isogenic cell lines expre...

  10. Chromium oxide nanoparticle-induced genotoxicity and p53-dependent apoptosis in human lung alveolar cells.

    Science.gov (United States)

    Senapati, Violet Aileen; Jain, Abhishek Kumar; Gupta, Govind Sharan; Pandey, Alok Kumar; Dhawan, Alok

    2015-10-01

    Chromium oxide (Cr2 O3 ) nanoparticles (NPs) are being increasingly used as a catalyst for aromatic compound manufacture, abrading agents and as pigments (e.g., Viridian). Owing to increased applications, it is important to study the biological effects of Cr2 O3 NPs on human health. The lung is one of the main exposure routes to nanomaterials; therefore, the present study was designed to determine the genotoxic and apoptotic effect of Cr2 O3 NPs in human lung epithelial cells (A549). The study also elucidated the molecular mechanism of its toxicity. Cr2 O3 NPs led to DNA damage, which was deduced by comet assay and cytokinesis block micronucleus assay. The damage could be mediated by the increased levels of reactive oxygen species. Further, the oxygen species led to a decrease in mitochondrial membrane potential and an increase in the ratio of BAX/Bcl-2 leading to mitochondria-mediated apoptosis induced by Cr2 O3 NPs, which ultimately leads to cell death. Hence, there is a need of regulations to be imposed in NP usage. The study provided insight into the caspase-dependent mechanistic pathway of apoptosis. PMID:26086747

  11. Tumor protein translationally controlled 1 is a p53 target gene that promotes cell survival

    OpenAIRE

    Chen, Weimin; Wang, Huihui; Tao, Shasha; Zheng, Yi; Wu, Wei; Lian, Fangru; Jaramillo, Melba; Fang, Deyu; Zhang, Donna D.

    2013-01-01

    Tumor suppressor p53 maintains genome stability by differentially activating target genes that control diverse cellular responses, such as the antioxidant response, cell cycle arrest and apoptosis. Despite the fact that many p53 downstream genes have been well characterized, novel p53 target genes are continuously being identified. Here, we report that Tpt1 is a direct target gene of p53. We found that p53 upregulates the transcription of Tpt1 and identified a p53-responsive element in the pr...

  12. Targeting Oncogenic Mutant p53 for Cancer Therapy

    OpenAIRE

    Parrales, Alejandro; Iwakuma, Tomoo

    2015-01-01

    Among genetic alterations in human cancers, mutations in the tumor suppressor p53 gene are the most common, occurring in over 50% of human cancers. The majority of p53 mutations are missense mutations and result in the accumulation of dysfunctional p53 protein in tumors. These mutants frequently have oncogenic gain-of-function activities and exacerbate malignant properties of cancer cells, such as metastasis and drug resistance. Increasing evidence reveals that stabilization of mutant p53 in ...

  13. Targeting the p53 Pathway in Ewing Sarcoma

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    Paul M. Neilsen

    2011-01-01

    Full Text Available The p53 tumour suppressor plays a pivotal role in the prevention of oncogenic transformation. Cancers frequently evade the potent antitumour surveillance mechanisms of p53 through mutation of the TP53 gene, with approximately 50% of all human malignancies expressing dysfunctional, mutated p53 proteins. Interestingly, genetic lesions in the TP53 gene are only observed in 10% of Ewing Sarcomas, with the majority of these sarcomas expressing a functional wild-type p53. In addition, the p53 downstream signaling pathways and DNA-damage cell cycle checkpoints remain functionally intact in these sarcomas. This paper summarizes recent insights into the functional capabilities and regulation of p53 in Ewing Sarcoma, with a particular focus on the cross-talk between p53 and the EWS-FLI1 gene rearrangement frequently associated with this disease. The development of several activators of p53 is discussed, with recent evidence demonstrating the potential of small molecule p53 activators as a promising systemic therapeutic approach for the treatment of Ewing Sarcomas with wild-type p53.

  14. p53 isoform Δ113p53 is a p53 target gene that antagonizes p53 apoptotic activity via BclxL activation in zebrafish

    OpenAIRE

    Chen, Jun; Ng, Sok Meng; Chang, Changqing; Zhang, Zhenhai; Bourdon, Jean-Christophe; Lane, David P.; Peng, Jinrong

    2009-01-01

    p53 is a well-known tumor suppressor and is also involved in processes of organismal aging and developmental control. A recent exciting development in the p53 field is the discovery of various p53 isoforms. One p53 isoform is human Δ133p53 and its zebrafish counterpart Δ113p53. These N-terminal-truncated p53 isoforms are initiated from an alternative p53 promoter, but their expression regulation and physiological significance at the organismal level are not well understood. We show here that ...

  15. Targeting oncogenic mutant p53 for cancer therapy

    OpenAIRE

    Tomoo eIwakuma; Alejandro eParrales

    2015-01-01

    Among genetic alterations in human cancers, mutations in the tumor suppressor p53 gene are the most common, occurring in over 50% of human cancers. The majority of p53 mutations are missense mutations and result in the accumulation of dysfunctional p53 protein in tumors. These mutants frequently have oncogenic gain-of-function (GOF) activities and exacerbate malignant properties of cancer cells, such as metastasis and drug resistance. Increasing evidence reveals that stabilization of mutant p...

  16. Targeting p53 for Novel Anticancer Therapy1

    OpenAIRE

    Wang, Zhen; Sun, Yi

    2010-01-01

    Carcinogenesis is a multistage process, involving oncogene activation and tumor suppressor gene inactivation as well as complex interactions between tumor and host tissues, leading ultimately to an aggressive metastatic phenotype. Among many genetic lesions, mutational inactivation of p53 tumor suppressor, the “guardian of the genome,” is the most frequent event found in 50% of human cancers. p53 plays a critical role in tumor suppression mainly by inducing growth arrest, apoptosis, and senes...

  17. Thick-target PIXE analysis of chromium, copper and arsenic impregnated lumber

    Science.gov (United States)

    Saarela, K.-E.; Harju, L.; Lill, J.-O.; Rajander, J.; Lindroos, A.; Heselius, S.-J.

    1999-04-01

    Chromium, copper and arsenic (CCA) have for decades been used for wood preservation. Of these elements especially arsenic is very toxic. As CCA impregnated wood is still today used for many construction purposes, a monitoring of these metal ions is of great environmental importance. Thick-target PIXE is a powerful method for the determination of trace metals in wood. The TTPIXE method enabled study of variations of the elemental concentrations in lumber treated with CCA impregnation solution. Distribution patterns were obtained for both naturally occurring elements and elements introduced in the treatment process. During the impregnation process a desorption of e.g. alkali metal ions takes place from the wood. The sensitivity of the method is improved by dry ashing of the samples prior to PIXE analysis. The TTPIXE method was calibrated and validated using international certified reference materials (CRM) based on wood material.

  18. 50 CFR 648.53 - Target total allowable catch, DAS allocations, and individual fishing quotas.

    Science.gov (United States)

    2010-10-01

    ... allocations, and individual fishing quotas. 648.53 Section 648.53 Wildlife and Fisheries FISHERY CONSERVATION... Target total allowable catch, DAS allocations, and individual fishing quotas. (a) Target total allowable... include the TAC for all scallop vessels fishing in open areas and Sea Scallop Access Areas, but...

  19. NGF-mediated transcriptional targets of p53 in PC12 neuronal differentiation

    Directory of Open Access Journals (Sweden)

    Labhart Paul

    2007-05-01

    Full Text Available Abstract Background p53 is recognized as a critical regulator of the cell cycle and apoptosis. Mounting evidence also suggests a role for p53 in differentiation of cells including neuronal precursors. We studied the transcriptional role of p53 during nerve growth factor-induced differentiation of the PC12 line into neuron-like cells. We hypothesized that p53 contributed to PC12 differentiation through the regulation of gene targets distinct from its known transcriptional targets for apoptosis or DNA repair. Results Using a genome-wide chromatin immunoprecipitation cloning technique, we identified and validated 14 novel p53-regulated genes following NGF treatment. The data show p53 protein was transcriptionally activated and contributed to NGF-mediated neurite outgrowth during differentiation of PC12 cells. Furthermore, we describe stimulus-specific regulation of a subset of these target genes by p53. The most salient differentiation-relevant target genes included wnt7b involved in dendritic extension and the tfcp2l4/grhl3 grainyhead homolog implicated in ectodermal development. Additional targets included brk, sdk2, sesn3, txnl2, dusp5, pon3, lect1, pkcbpb15 and other genes. Conclusion Within the PC12 neuronal context, putative p53-occupied genomic loci spanned the entire Rattus norvegicus genome upon NGF treatment. We conclude that receptor-mediated p53 transcriptional activity is involved in PC12 differentiation and may suggest a contributory role for p53 in neuronal development.

  20. Inactivation and inducible oncogenic mutation of p53 in gene targeted pigs.

    Directory of Open Access Journals (Sweden)

    Simon Leuchs

    Full Text Available Mutation of the tumor suppressor p53 plays a major role in human carcinogenesis. Here we describe gene-targeted porcine mesenchymal stem cells (MSCs and live pigs carrying a latent TP53(R167H mutant allele, orthologous to oncogenic human mutant TP53(R175H and mouse Trp53(R172H, that can be activated by Cre recombination. MSCs carrying the latent TP53(R167H mutant allele were analyzed in vitro. Homozygous cells were p53 deficient, and on continued culture exhibited more rapid proliferation, anchorage independent growth, and resistance to the apoptosis-inducing chemotherapeutic drug doxorubicin, all characteristic of cellular transformation. Cre mediated recombination activated the latent TP53(R167H allele as predicted, and in homozygous cells expressed mutant p53-R167H protein at a level ten-fold greater than wild-type MSCs, consistent with the elevated levels found in human cancer cells. Gene targeted MSCs were used for nuclear transfer and fifteen viable piglets were produced carrying the latent TP53(R167H mutant allele in heterozygous form. These animals will allow study of p53 deficiency and expression of mutant p53-R167H to model human germline, or spontaneous somatic p53 mutation. This work represents the first inactivation and mutation of the gatekeeper tumor suppressor gene TP53 in a non-rodent mammal.

  1. Progress in the chemistry of chromium(V) doping agents used in polarized target materials

    Energy Technology Data Exchange (ETDEWEB)

    Krumpolc, M. (Illinois Univ., Chicago, IL (USA)); Hill, D. (Argonne National Lab., IL (USA)); Struhrmann, H.B. (Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany, F.R.). Hamburger Synchrotronstrahlungslabor)

    1990-01-01

    We wish to report progress in two areas of the chromium (V)-based doping agents: Two commonly used chromium (V) complexes, I and II, have been synthesized in perdeuterated form (i.e., all hydrogens replaced by deuterium). They are sodium bis(2-ethyl-2-deuteroxy-butyrato)oxochromate(V)monodeuterate, IV, (acronym EDBA-Cr(V)), and sodium bis(2-deuteroxy-2-methylpropionato)oxochromate(V), III, (acronym DMPA-Cr(V)). A synthetic route leading to the preparation of stable, chromium(III)-free solutions of chromium(V) in diols (1,2-ethanediol/ethylene glycol/and 1,2-propanediol/propylene glycol/) has been outlined.

  2. Isolation and characterization of DUSP11, a novel p53 target gene

    DEFF Research Database (Denmark)

    Caprara, Greta; Zamponi, Raffaella; Melixetian, Marina;

    2009-01-01

    ABSTRACT p53 regulates the expression of genes involved in cell cycle control, apoptosis and DNA damage repair. Here we demonstrate that DUSP11 (Dual Specificity Phosphatase 11), a member of the Protein Tyrosine Phosphatase family that binds to RNA-RNP complexes and RNA splicing factors, is a p53...... target gene. Consistent with this, the expression of DUSP11 is induced in a p53-dependent manner after treatment with DNA damaging agents. Chromatin immunoprecipitation analysis showed that p53 binds to 2 putative p53 DNA binding sites in the promoter region of DUSP11. Colony formation and proliferation...... (Src-Associated protein in Mitotic cells) binds to DUSP11 in vitro and in vivo. Taken together these results suggest that DUSP11 contributes to p53-dependent inhibition of cell proliferation and that it might be involved in regulating RNA splicing through SAM68....

  3. Noncanonical DNA motifs as transactivation targets by wild type and mutant p53.

    Directory of Open Access Journals (Sweden)

    Jennifer J Jordan

    2008-06-01

    Full Text Available Sequence-specific binding by the human p53 master regulator is critical to its tumor suppressor activity in response to environmental stresses. p53 binds as a tetramer to two decameric half-sites separated by 0-13 nucleotides (nt, originally defined by the consensus RRRCWWGYYY (n = 0-13 RRRCWWGYYY. To better understand the role of sequence, organization, and level of p53 on transactivation at target response elements (REs by wild type (WT and mutant p53, we deconstructed the functional p53 canonical consensus sequence using budding yeast and human cell systems. Contrary to early reports on binding in vitro, small increases in distance between decamer half-sites greatly reduces p53 transactivation, as demonstrated for the natural TIGER RE. This was confirmed with human cell extracts using a newly developed, semi-in vitro microsphere binding assay. These results contrast with the synergistic increase in transactivation from a pair of weak, full-site REs in the MDM2 promoter that are separated by an evolutionary conserved 17 bp spacer. Surprisingly, there can be substantial transactivation at noncanonical (1/2-(a single decamer and (3/4-sites, some of which were originally classified as biologically relevant canonical consensus sequences including PIDD and Apaf-1. p53 family members p63 and p73 yielded similar results. Efficient transactivation from noncanonical elements requires tetrameric p53, and the presence of the carboxy terminal, non-specific DNA binding domain enhanced transactivation from noncanonical sequences. Our findings demonstrate that RE sequence, organization, and level of p53 can strongly impact p53-mediated transactivation, thereby changing the view of what constitutes a functional p53 target. Importantly, inclusion of (1/2- and (3/4-site REs greatly expands the p53 master regulatory network.

  4. FATS is a transcriptional target of p53 and associated with antitumor activity

    Directory of Open Access Journals (Sweden)

    Zhang Xifeng

    2010-09-01

    Full Text Available Abstract Frequent mutations of p53 in human cancers exemplify its crucial role as a tumor suppressor transcription factor, and p21, a transcriptional target of p53, plays a central role in surveillance of cell-cycle checkpoints. Our previous study has shown that FATS stabilize p21 to preserve genome integrity. In this study we identified a novel transcript variant of FATS (GenBank: GQ499374 through screening a cDNA library from mouse testis, which uncovered the promoter region of mouse FATS. Mouse FATS was highly expressed in testis. The p53-responsive elements existed in proximal region of both mouse and human FATS promoters. Functional study indicated that the transcription of FATS gene was activated by p53, whereas such effect was abolished by site-directed mutagenesis in the p53-RE of FATS promoter. Furthermore, the expression of FATS increased upon DNA damage in a p53-dependent manner. FATS expression was silent or downregulated in human cancers, and overexpression of FATS suppressed tumorigenicity in vivo independently of p53. Our results reveal FATS as a p53-regulated gene to monitor genomic stability.

  5. Evaluation of sgRNA target sites for CRISPR-mediated repression of TP53.

    Directory of Open Access Journals (Sweden)

    Ingrid E B Lawhorn

    Full Text Available The CRISPR (clustered regularly interspaced short palindromic repeats platform has been developed as a general method to direct proteins of interest to gene targets. While the native CRISPR system delivers a nuclease that cleaves and potentially mutates target genes, researchers have recently employed catalytically inactive CRISPR-associated 9 nuclease (dCas9 in order to target and repress genes without DNA cleavage or mutagenesis. With the intent of improving repression efficiency in mammalian cells, researchers have also fused dCas9 with a KRAB repressor domain. Here, we evaluated different genomic sgRNA targeting sites for repression of TP53. The sites spanned a 200-kb distance, which included the promoter, transcript sequence, and regions flanking the endogenous human TP53 gene. We showed that repression up to 86% can be achieved with dCas9 alone (i.e., without use of the KRAB domain by targeting the complex to sites near the TP53 transcriptional start site. This work demonstrates that efficient transcriptional repression of endogenous human genes can be achieved by the targeted delivery of dCas9. Yet, the efficiency of repression strongly depends on the choice of the sgRNA target site.

  6. USP7 Enforces Heterochromatinization of p53 Target Promoters by Protecting SUV39H1 from MDM2-Mediated Degradation

    OpenAIRE

    Sathish Kumar Mungamuri; Rui F. Qiao; Shen Yao; James J. Manfredi; Wei Gu; Stuart A. Aaronson

    2016-01-01

    The H3K9me3 repressive histone conformation of p53 target promoters is abrogated in response to p53 activation by MDM2-mediated SUV39H1 degradation. Here, we present evidence that the USP7 deubiquitinase protects SUV39H1 from MDM2-mediated ubiquitination in the absence of p53 stimulus. USP7 occupies p53 target promoters in unstressed conditions, a process that is abrogated with p53 activation associated with loss of the H3K9me3 mark on these same promoters. Mechanistically, USP7 forms a trime...

  7. SPATA18, a Spermatogenesis-Associated Gene, Is a Novel Transcriptional Target of p53 and p63▿

    OpenAIRE

    Bornstein, Chamutal; Brosh, Ran; Molchadsky, Alina; Madar, Shalom; Kogan-Sakin, Ira; Goldstein, Ido; Chakravarti, Deepavali; Flores, Elsa R.; Goldfinger, Naomi; Sarig, Rachel; Rotter, Varda

    2011-01-01

    The transcription factor p53 functions not only to suppress tumorigenesis but also to maintain normal development and homeostasis. Although p53 was implicated in different aspects of fertility, including spermatogenesis and implantation, the mechanism underlying p53 involvement in spermatogenesis is poorly resolved. In this study we describe the identification of a spermatogenesis-associated gene, SPATA18, as a novel p53 transcriptional target and show that SPATA18 transcription is induced by...

  8. Detection of p53 overexpression in routinely paraffin-embedded tissue of human carcinomas using a novel target unmasking fluid.

    OpenAIRE

    van den Berg, F M; Baas, I O; Polak, M. M.; Offerhaus, G. J.

    1993-01-01

    With the aid of a newly developed target unmasking fluid (TUF), p53 overexpression was visualized by immunohistochemistry on recent and archival paraffin-embedded tissue samples of colon, stomach, and pancreas neoplasms. Using monoclonal anti-p53 antibody pAb1801 as well as polyclonal antiserum to p53 CM1, TUF-mediated immunohistochemistry was fully concordant for p53 overexpression in paraffin-embedded carcinoma samples compared with freshly frozen tissue from the same tumors. Thus, prognost...

  9. Apaf-1 is a transcriptional target for E2F and p53

    DEFF Research Database (Denmark)

    Moroni, M C; Hickman, E S; Lazzerini Denchi, E;

    2001-01-01

    Loss of function of the retinoblastoma protein, pRB, leads to lack of differentiation, hyperproliferation and apoptosis. Inactivation of pRB results in deregulated E2F activity, which in turn induces entry to S-phase and apoptosis. Induction of apoptosis by either the loss of pRB...... between the deregulation of the pRB pathway and apoptosis. Furthermore, because the pRB pathway is functionally inactivated in most cancers, the identification of Apaf-1 as a transcriptional target for E2F might explain the increased sensitivity of tumour cells to chemotherapy. We also show that......, independently of the pRB pathway, Apaf-1 is a direct transcriptional target of p53, suggesting that p53 might sensitize cells to apoptosis by increasing Apaf-1 levels....

  10. Ranked prediction of p53 targets using hidden variable dynamic modeling

    OpenAIRE

    Barenco, M.; Tomescu, D; Brewer, D; Callard, R.; Stark, J.(Laboratoire de Physique Subatomique et de Cosmologie, Université Grenoble-Alpes, CNRS/IN2P3, Grenoble, France); Hubank, M.

    2006-01-01

    Full exploitation of microarray data requires hidden information that cannot be extracted using current analysis methodologies. We present a new approach, hidden variable dynamic modeling (HVDM), which derives the hidden profile of a transcription factor from time series microarray data, and generates a ranked list of predicted targets. We applied HVDM to the p53 network, validating predictions experimentally using small interfering RNA. HVDM can be applied in many systems biology contexts to...

  11. Fuzzy tandem repeats containing p53 response elements may define species-specific p53 target genes.

    Directory of Open Access Journals (Sweden)

    Iva Simeonova

    2012-06-01

    Full Text Available Evolutionary forces that shape regulatory networks remain poorly understood. In mammals, the Rb pathway is a classic example of species-specific gene regulation, as a germline mutation in one Rb allele promotes retinoblastoma in humans, but not in mice. Here we show that p53 transactivates the Retinoblastoma-like 2 (Rbl2 gene to produce p130 in murine, but not human, cells. We found intronic fuzzy tandem repeats containing perfect p53 response elements to be important for this regulation. We next identified two other murine genes regulated by p53 via fuzzy tandem repeats: Ncoa1 and Klhl26. The repeats are poorly conserved in evolution, and the p53-dependent regulation of the murine genes is lost in humans. Our results indicate a role for the rapid evolution of tandem repeats in shaping differences in p53 regulatory networks between mammalian species.

  12. p53 gene targeting by homologous recombination in fish ES cells.

    Directory of Open Access Journals (Sweden)

    Yan Yan

    Full Text Available BACKGROUND: Gene targeting (GT provides a powerful tool for the generation of precise genetic alterations in embryonic stem (ES cells to elucidate gene function and create animal models for human diseases. This technology has, however, been limited to mouse and rat. We have previously established ES cell lines and procedures for gene transfer and selection for homologous recombination (HR events in the fish medaka (Oryzias latipes. METHODOLOGY AND PRINCIPAL FINDINGS: Here we report HR-mediated GT in this organism. We designed a GT vector to disrupt the tumor suppressor gene p53 (also known as tp53. We show that all the three medaka ES cell lines, MES1∼MES3, are highly proficient for HR, as they produced detectable HR without drug selection. Furthermore, the positive-negative selection (PNS procedure enhanced HR by ∼12 folds. Out of 39 PNS-resistant colonies analyzed, 19 (48.7% were positive for GT by PCR genotyping. When 11 of the PCR-positive colonies were further analyzed, 6 (54.5% were found to be bona fide homologous recombinants by Southern blot analysis, sequencing and fluorescent in situ hybridization. This produces a high efficiency of up to 26.6% for p53 GT under PNS conditions. We show that p53 disruption and long-term propagation under drug selection conditions do not compromise the pluripotency, as p53-targeted ES cells retained stable growth, undifferentiated phenotype, pluripotency gene expression profile and differentiation potential in vitro and in vivo. CONCLUSIONS: Our results demonstrate that medaka ES cells are proficient for HR-mediated GT, offering a first model organism of lower vertebrates towards the development of full ES cell-based GT technology.

  13. APAF1 is a key transcriptional target for p53 in the regulation of neuronal cell death

    DEFF Research Database (Denmark)

    Fortin, A; Cregan, S P; MacLaurin, J G;

    2001-01-01

    p53 is a transcriptional activator which has been implicated as a key regulator of neuronal cell death after acute injury. We have shown previously that p53-mediated neuronal cell death involves a Bax-dependent activation of caspase 3; however, the transcriptional targets involved in the regulation...... of this process have not been identified. In the present study, we demonstrate that p53 directly upregulates Apaf1 transcription as a critical step in the induction of neuronal cell death. Using DNA microarray analysis of total RNA isolated from neurons undergoing p53-induced apoptosis a 5-6-fold upregulation...... of Apaf1 mRNA was detected. Induction of neuronal cell death by camptothecin, a DNA-damaging agent that functions through a p53-dependent mechanism, resulted in increased Apaf1 mRNA in p53-positive, but not p53-deficient neurons. In both in vitro and in vivo neuronal cell death processes of p53-induced...

  14. Antisense oligonucleotide targeting p53 increased apoptosis of MCF-7 cells induced by ionizing radiation

    Institute of Scientific and Technical Information of China (English)

    Li-cheng DAI; Xiang WANG; Xing YAO; Li-shan MIN; Fu-chu QIAN; Jian-fang HE

    2006-01-01

    Aim: To investigate the effect of antisense compounds (AS) targeting human p53 mRNA on radiosensitivity of MCF-7 cells. Methods: Western blotting and RT-PCR were used to analyze the protein content and mRNA level. Additionally, cell proliferation, cell cycle and cell apoptosis were all analyzed in irradiated or sham-irradiated cells. Results: Among the five antisense compounds (AS), AS3 was identified to efficiently inhibit p53 mRNA level and protein content. Interestingly, ASS transfer has little effect on cell proliferation in DU-145 cells (mutant p53) after ionizing radiation (IR). In contrast, a marked increase of cell apoptosis and growth inhibition were observed in MCF-7 cells (wild-type p53), suggesting that AS3 can increase radiosensitivity of MCF-7 cells. Additionally, it was also observed that the transfection of AS3 decreased the fraction of G1 phase cells, and increased the proportion of S phase cells compared to untreated cells 24 h after IR in MCF-7 cell lines. Conclusion: AS3 transfection increases MCF-7 cell apoptosis induced by 5 Gy-radiation, and this mechanism may be closely associated with abrogation of G1 phase arrest.

  15. SPATA18, a Spermatogenesis-Associated Gene, Is a Novel Transcriptional Target of p53 and p63▿

    Science.gov (United States)

    Bornstein, Chamutal; Brosh, Ran; Molchadsky, Alina; Madar, Shalom; Kogan-Sakin, Ira; Goldstein, Ido; Chakravarti, Deepavali; Flores, Elsa R.; Goldfinger, Naomi; Sarig, Rachel; Rotter, Varda

    2011-01-01

    The transcription factor p53 functions not only to suppress tumorigenesis but also to maintain normal development and homeostasis. Although p53 was implicated in different aspects of fertility, including spermatogenesis and implantation, the mechanism underlying p53 involvement in spermatogenesis is poorly resolved. In this study we describe the identification of a spermatogenesis-associated gene, SPATA18, as a novel p53 transcriptional target and show that SPATA18 transcription is induced by p53 in a variety of cell types of both human and mouse origin. p53 binds a consensus DNA motif that resides within the first intron of SPATA18. We describe the spatiotemporal expression patterns of SPATA18 in mouse seminiferous tubules and suggest that SPATA18 transcription is regulated in vivo by p53. We also demonstrate the induction of SPATA18 by p63 and suggest that p63 can compensate for the loss of p53 activity in vivo. Our data not only enrich the known collection of p53 targets but may also provide insights on spermatogenesis defects that are associated with p53 deficiency. PMID:21300779

  16. Targeting the MDM2/MDM4 interaction interface as a promising approach for p53 reactivation therapy.

    Science.gov (United States)

    Pellegrino, Marsha; Mancini, Francesca; Lucà, Rossella; Coletti, Alice; Giacchè, Nicola; Manni, Isabella; Arisi, Ivan; Florenzano, Fulvio; Teveroni, Emanuela; Buttarelli, Marianna; Fici, Laura; Brandi, Rossella; Bruno, Tiziana; Fanciulli, Maurizio; D'Onofrio, Mara; Piaggio, Giulia; Pellicciari, Roberto; Pontecorvi, Alfredo; Marine, Jean Christophe; Macchiarulo, Antonio; Moretti, Fabiola

    2015-11-01

    Restoration of wild-type p53 tumor suppressor function has emerged as an attractive anticancer strategy. Therapeutics targeting the two p53-negative regulators, MDM2 and MDM4, have been developed, but most agents selectively target the ability of only one of these molecules to interact with p53, leaving the other free to operate. Therefore, we developed a method that targets the activity of MDM2 and MDM4 simultaneously based on recent studies indicating that formation of MDM2/MDM4 heterodimer complexes are required for efficient inactivation of p53 function. Using computational and mutagenesis analyses of the heterodimer binding interface, we identified a peptide that mimics the MDM4 C-terminus, competes with endogenous MDM4 for MDM2 binding, and activates p53 function. This peptide induces p53-dependent apoptosis in vitro and reduces tumor growth in vivo. Interestingly, interfering with the MDM2/MDM4 heterodimer specifically activates a p53-dependent oxidative stress response. Consistently, distinct subcellular pools of MDM2/MDM4 complexes were differentially sensitive to the peptide; nuclear MDM2/MDM4 complexes were particularly highly susceptible to the peptide-displacement activity. Taken together, these data identify the MDM2/MDM4 interaction interface as a valuable molecular target for therapeutic reactivation of p53 oncosuppressive function. PMID:26359458

  17. Translational approaches targeting the p53 pathway for anti-cancer therapy

    OpenAIRE

    Essmann, Frank; Schulze-Osthoff, Klaus

    2012-01-01

    The p53 tumour suppressor blocks cancer development by triggering apoptosis or cellular senescence in response to oncogenic stress or DNA damage. Consequently, the p53 signalling pathway is virtually always inactivated in human cancer cells. This unifying feature has commenced tremendous efforts to develop p53-based anti-cancer therapies. Different strategies exist that are adapted to the mechanisms of p53 inactivation. In p53-mutated tumours, delivery of wild-type p53 by adenovirus-based gen...

  18. Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease.

    Science.gov (United States)

    Hill, Rebecca M; Kuijper, Sanne; Lindsey, Janet C; Petrie, Kevin; Schwalbe, Ed C; Barker, Karen; Boult, Jessica K R; Williamson, Daniel; Ahmad, Zai; Hallsworth, Albert; Ryan, Sarra L; Poon, Evon; Robinson, Simon P; Ruddle, Ruth; Raynaud, Florence I; Howell, Louise; Kwok, Colin; Joshi, Abhijit; Nicholson, Sarah Leigh; Crosier, Stephen; Ellison, David W; Wharton, Stephen B; Robson, Keith; Michalski, Antony; Hargrave, Darren; Jacques, Thomas S; Pizer, Barry; Bailey, Simon; Swartling, Fredrik J; Weiss, William A; Chesler, Louis; Clifford, Steven C

    2015-01-12

    We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 function in this model produced aggressive tumors that mimicked characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity and genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53-MYC interactions at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically. PMID:25533335

  19. Release of targeted p53 from the mitochondrion as an early signal during mitochondrial dysfunction

    Science.gov (United States)

    Increased accumulation of p53 tumor suppressor protein is an early response to low-level stressors. To investigate the fate of mitochondrial-sequestered p53, mouse embryonic fibroblast cells (MEFs) on a p53-deficient genetic background were transfected with p53-EGFP fusion protei...

  20. Posttranscriptional Regulation of p53 and Its Targets by RNA-Binding Proteins

    OpenAIRE

    Zhang, Jin; Chen, Xinbin

    2008-01-01

    p53 tumor suppressor plays a pivotal role in maintaining genomic integrity and preventing cancer development. The importance of p53 in tumor suppression is illustrated by the observation that about 50% human tumor cells have a dysfunctional p53 pathway. Although it has been well accepted that the activity of p53 is mainly controlled through post-translational modifications, recent studies have revealed that posttranscriptional regulations of p53 by various RNA-binding proteins also play a cru...

  1. Targeting of p300/CREB binding protein coactivators by simian virus 40 is mediated through p53.

    Science.gov (United States)

    Borger, Darrell R; DeCaprio, James A

    2006-05-01

    The primary transforming functions of simian virus 40 large T antigen (SV40 LT) are conferred primarily through the binding and inactivation of p53 and the retinoblastoma family members. Normal p53 function requires an association with the CREB binding protein (CBP)/p300 coactivators, and a ternary complex containing SV40 LT, p53, and CBP/p300 has been identified previously. In this report, we have evaluated a secondary function of p53 bound to the SV40 LT complex in mediating the binding of human CBP/p300. We demonstrate that p53 associated with SV40 LT was posttranslationally modified in a manner consistent with the binding of CBP/p300. Furthermore, expression of SV40 LT induced the proportion of p53 phosphorylated on S15. An essential function for p53 in bridging the interaction between SV40 LT and CBP/p300 was identified through the reconstitution of the SV40 LT-CBP/p300 complex upon p53 reexpression in p53-null cells. In addition, the SV40 LT-CBP/p300 complex was disrupted through RNA interference-mediated depletion of endogenous p53. We also demonstrate that SV40 LT was acetylated in a p300- and p53-dependent manner, at least in part through the CH3 domain of p300. Therefore, the binding of p53 serves to modify SV40 LT by targeting CBP and p300 binding to direct the acetylation of SV40 LT. PMID:16611888

  2. Evodiamine selectively targets cancer stem-like cells through the p53-p21-Rb pathway.

    Science.gov (United States)

    Han, Seula; Woo, Jong Kyu; Jung, Yuchae; Jeong, Dawoon; Kang, Minsook; Yoo, Young-Ji; Lee, Hani; Oh, Seung Hyun; Ryu, Jae-Ha; Kim, Woo-Young

    2016-01-22

    In spite of the recent improvements, the resistance to chemotherapy/radiotherapy followed by relapse is the main hurdle for the successful treatment of breast cancer, a leading cause of death in women. A small population of breast cancer cells that have stem-like characteristics (cancer stem-like cells; CSLC) may contribute to this resistance and relapse. Here, we report on a component of a traditional Chinese medicine, evodiamine, which selectively targets CSLC of breast cancer cell lines MCF7 and MDAMB 231 at a concentration that does show a little or no cytotoxic effect on bulk cancer cells. While evodiamine caused the accumulation of bulk cancer cells at the G2/M phase, it did not hold CSLC in a specific cell cycle phase but instead, selectively killed CSLC. This was not due to the culture of CSLC in suspension or without FBS. A proteomic analysis and western blotting revealed that evodiamine changed the expression of cell cycle regulating molecules more efficiently in CSLC cells than in bulk cancer cells. Surprisingly, evodiamine selectively activated p53 and p21 and decreased inactive Rb, the master molecules in G1/S checkpoint. These data collectively suggest a novel mechanism involving CSLC-specific targeting by evodiamine and its possible use to the therapy of breast cancer.

  3. Identification of Semaphorin3B as a Direct Target of p53

    Directory of Open Access Journals (Sweden)

    Kensuke Ochi

    2002-01-01

    Full Text Available A cDNA microarray analysis indicated that Semaphorin3B. (20Sema3B, a gene whose product is involved in axon guidance and axonal repulsion, is inducible by p53. Introduction of exogenous p53 into a glioblastoma cell line lacking wild-type p53. (20U373MG dramatically induced expression of Sema3B mRNA. An electrophoretic mobility shift assay and a reporter assay confirmed that a potential p53 binding site present in the promoter region had p53-dependent transcriptional activity. Expression of endogenous Sema3B was induced in response to genotoxic stresses caused by adriamycin treatment or UV irradiation in a p53-dependent manner. Ectopic expression of Sema3B in p53-defective cells reduced the number of colonies in colony formation assays. These results suggest that Sema3B might play some role in regulating cell growth as a mediator of p53 tumor- suppressor activity.

  4. miR-339-5p regulates the p53 tumor-suppressor pathway by targeting MDM2

    DEFF Research Database (Denmark)

    Jansson, M D; Djodji Damas, Nkerorema; Lees, M;

    2014-01-01

    proliferation in response to stress and represents the most commonly lost and mutated gene in human cancers. The function of p53 is inhibited by the MDM2 oncoprotein. Using a high-throughput screening approach, we identified miR-339-5p as a regulator of the p53 pathway. We demonstrate that this regulation...... occurs via the ability of miR-339-5p to target directly the 3'-untranslated region of MDM2 mRNA, reducing MDM2 expression and thus promoting p53 function. Consequently, overexpression of miR-339-5p positively impacts on p53-governed cellular responses such as proliferation arrest and senescence, whereas...... inhibition of miR-339-5p function perturbs the p53 response in cancer cells, allowing an increased proliferation rate. In addition, miR-339-5p expression is downregulated in tumors harboring wild-type TP53, suggesting that reduction of miR-339-5p level helps to suppress the p53 response in p53-competent...

  5. Translational regulation of p53 as a potential tumor therapy target

    NARCIS (Netherlands)

    B. Schumacher (Björn); A. Gartner (Anton)

    2006-01-01

    textabstractThe tumor suppressor p53 is a central player in apoptosis induction in response to oncogenic stimuli and DNA damage. As activation of p53 has been suggested as a prime strategy for future tumor therapy, inhibition of negative regulators of p53 activity would be a similarly desirable stra

  6. Regulation of p53-targeting microRNAs by polycyclic aromatic hydrocarbons: Implications in the etiology of multiple myeloma.

    Science.gov (United States)

    Gordon, Michael W; Yan, Fang; Zhong, Xiaoming; Mazumder, Pranab Behari; Xu-Monette, Zijun Y; Zou, Dehui; Young, Ken H; Ramos, Kenneth S; Li, Yong

    2015-10-01

    Multiple myeloma (MM) is a common and deadly cancer of blood plasma cells. A unique feature of MM is the extremely low somatic mutation rate of the p53 tumor suppressor gene, in sharp contrast with about half of all human cancers where this gene is frequently mutated. Eleven miRNAs have been reported to repress p53 through direct interaction with the 3' untranslated region. The expression of nine of them is higher in MM plasma cells than in healthy donor counterparts, suggesting that miRNA overexpression is responsible for p53 inactivation in MM. Here, we report that the environmental carcinogen benzo[a]pyrene (BaP) upregulated the expression of seven p53-targeting miRNAs (miR-25, miR-15a, miR-16, miR-92, miR-125b, miR-141, and miR-200a), while 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD) upregulated two of them (miR-25 and miR-92) in MM cells. The miR-25 promoter was activated by both BaP and TCDD, and this response was mediated by the aryl hydrocarbon receptor (AhR). We screened 727 compounds that inhibit MM cell survival and down-regulate the expression of p53-targeting miRNAs. We found that (-)-epigallocatechin-3-gallate (EGCG), a constituent of green tea and a major component of the botanical drug Polyphenon® E, reduced the expression of four p53-targeting miRNAs, including miR-25, miR-92, miR-141, and miR-200a. Collectively, these data implicate polycyclic aromatic hydrocarbons and AhR in the regulation of p53-targeting miRNAs in MM and identify a potential therapeutic and preventive agent to combat this deadly disease. PMID:24798859

  7. p53-induced microRNA-1246 inhibits the cell growth of human hepatocellular carcinoma cells by targeting NFIB.

    Science.gov (United States)

    Zhang, Quan; Cao, Li-Ye; Cheng, Shu-Jie; Zhang, Ai-Min; Jin, Xiao-Shi; Li, Yong

    2015-03-01

    In recent years, miR-1246 has been identified as a transcriptional target of p53 in Down syndrome and may provide a new p53-miR-1246-DYRK1A-NFAT pathway in cancer. The present study aimed to explore the role of miR-1246 in the tumorigenesis of human hepatocellular carcinoma (HCC). We found that wild-type p53 regulated the expression of miR-1246 in HCC cell lines, and alteration of miR-1246 modulated cell proliferation, colony formation ability and apoptosis. The nuclear factor I/B (NFIB), an oncogene, was identified as a direct target gene of miR-1246 using a fluorescent reporter assay. Overexpression of NFIB abolished the regulation of cell apoptosis caused by miR-1246 in HepG2 cells. This finding suggests that miR-1246 is regulated by p53 and suppresses the growth of human HCC by targeting NFIB. Here, we propose a new p53-miR-1246-NFIB pathway in HCC. PMID:25591821

  8. p53 targets simian virus 40 large T antigen for acetylation by CBP.

    Science.gov (United States)

    Poulin, Danielle L; Kung, Andrew L; DeCaprio, James A

    2004-08-01

    Simian virus 40 (SV40) large T antigen (T Ag) interacts with the tumor suppressor p53 and the transcriptional coactivators CBP and p300. Binding of these cellular proteins in a ternary complex has been implicated in T Ag-mediated transformation. It has been suggested that the ability of CBP/p300 to modulate p53 function underlies p53's regulation of cell proliferation and tumorigenesis. In this study, we provide further evidence that CBP activity may be mediated through its synergistic action with p53. We demonstrate that SV40 T Ag is acetylated in vivo in a p53-dependent manner and T Ag acetylation is largely mediated by CBP. The acetylation of T Ag is dependent on its interaction with p53 and on p53's interaction with CBP. We have mapped the site of acetylation on T Ag to the C-terminal lysine residue 697. This acetylation site is conserved between the T antigens of the human polyomaviruses JC and BK, which are also known to interact with p53. We show that both JC and BK T antigens are also acetylated at corresponding sites in vivo. While other proteins are known to be acetylated by CBP/p300, none are known to depend on p53 for acetylation. T Ag acetylation may provide a regulatory mechanism for T Ag binding to a cellular factor or play a role in another aspect of T Ag function. PMID:15254196

  9. ISG20L1 is a p53 family target gene that modulates genotoxic stress-induced autophagy

    Directory of Open Access Journals (Sweden)

    Johnson Kimberly N

    2010-04-01

    Full Text Available Abstract Background Autophagy is characterized by the sequestration of cytoplasm and organelles into multimembrane vesicles and subsequent degradation by the cell's lysosomal system. It is linked to many physiological functions in human cells including stress response, protein degradation, organelle turnover, caspase-independent cell death and tumor suppression. Malignant transformation is frequently associated with deregulation of autophagy and several tumor suppressors can modulate autophagic processes. The tumor suppressor p53 can induce autophagy after metabolic or genotoxic stress through transcriptionally-dependent and -independent mechanisms. In this study we expand on the former mechanism by functionally characterizing a p53 family target gene, ISG20L1 under conditions of genotoxic stress. Results We identified a p53 target gene, ISG20L1, and show that transcription of the gene can be regulated by all three p53 family members (p53, p63, and p73. We generated an antibody to ISG20L1 and found that it localizes to the nucleolar and perinucleolar regions of the nucleus and its protein levels increase in a p53- and p73-dependent manner after various forms of genotoxic stress. When ectopically expressed in epithelial cancer-derived cell lines, ISG20L1 expression decreased clonogenic survival without a concomitant elevation in apoptosis and this effect was partially rescued in cells that were ATG5 deficient. Knockdown of ISG20L1 did not alter 5-FU induced apoptosis as assessed by PARP and caspase-3 cleavage, sub-G1 content, and DNA laddering. Thus, we investigated the role of ISG20L1 in autophagy, a process commonly associated with type II cell death, and found that ISG20L1 knockdown decreased levels of autophagic vacuoles and LC3-II after genotoxic stress as assessed by electron microscopy, biochemical, and immunohistochemical measurements of LC3-II. Conclusions Our identification of ISG20L1 as a p53 family target and discovery that modulation

  10. Physical exercise regulates p53 activity targeting SCO2 and increases mitochondrial COX biogenesis in cardiac muscle with age.

    Directory of Open Access Journals (Sweden)

    Zhengtang Qi

    Full Text Available The purpose of this study was to outline the timelines of mitochondrial function, oxidative stress and cytochrome c oxidase complex (COX biogenesis in cardiac muscle with age, and to evaluate whether and how these age-related changes were attenuated by exercise. ICR/CD-1 mice were treated with pifithrin-μ (PFTμ, sacrificed and studied at different ages; ICR/CD-1 mice at younger or older ages were randomized to endurance treadmill running and sedentary conditions. The results showed that mRNA expression of p53 and its protein levels in mitochondria increased with age in cardiac muscle, accompanied by increased mitochondrial oxidative stress, reduced expression of COX subunits and assembly proteins, and decreased expression of most markers in mitochondrial biogenesis. Most of these age-related changes including p53 activity targeting cytochrome oxidase deficient homolog 2 (SCO2, p53 translocation to mitochondria and COX biogenesis were attenuated by exercise in older mice. PFTμ, an inhibitor blocking p53 translocation to mitochondria, increased COX biogenesis in older mice, but not in young mice. Our data suggest that physical exercise attenuates age-related changes in mitochondrial COX biogenesis and p53 activity targeting SCO2 and mitochondria, and thereby induces antisenescent and protective effects in cardiac muscle.

  11. Resuscitation of wild-type p53 expression by disrupting ceramide glycosylation: a novel approach to target mutant p53 tumors

    OpenAIRE

    Liu, Yong-Yu

    2011-01-01

    Mutant p53 is frequently detected in cancers lose of its ability in tumor suppression and gain of function in promoting tumor progression. Restoration of p53 functions by replacement of wild-type p53 and inhibition of its degradation or increment of its transcriptional activity has been applied in prevention and treatment of cancers. Recent evidence indicates that disrupting ceramide glycosylation can resuscitate wild-type p53 expression and p53-dependent apoptosis in mutant p53 tumors. Actin...

  12. p53 Targets Simian Virus 40 Large T Antigen for Acetylation by CBP

    OpenAIRE

    Poulin, Danielle L.; Kung, Andrew L.; DeCaprio, James A.

    2004-01-01

    Simian virus 40 (SV40) large T antigen (T Ag) interacts with the tumor suppressor p53 and the transcriptional coactivators CBP and p300. Binding of these cellular proteins in a ternary complex has been implicated in T Ag-mediated transformation. It has been suggested that the ability of CBP/p300 to modulate p53 function underlies p53's regulation of cell proliferation and tumorigenesis. In this study, we provide further evidence that CBP activity may be mediated through its synergistic action...

  13. Suppression of Id2, a member of the inhibitor of differentiation family and a target of mutant p53, is required for mutant p53 gain of function

    OpenAIRE

    Yan, Wensheng; Liu, Gang; Scoumanne, Ariane; Chen, Xinbin

    2008-01-01

    Over-expression of mutant p53 is a common theme in human tumors, suggesting a tumor-promoting gain of function for mutant p53. To elucidate whether and how mutant p53 acquires its gain of function, mutant p53 is inducibly knocked down in SW480 colon cancer cell line, which contains mutant p53(R273H/P309S), and MIA-PaCa-2 pancreatic cancer cell line, which contains mutant p53(R248W). We found that knockdown of mutant p53 markedly inhibits cell proliferation. In addition, knockdown of mutant p5...

  14. IGFBP7 is a p53 target gene inactivated in human lung cancer by DNA hypermethylation.

    Science.gov (United States)

    Chen, Yuan; Cui, Tiantian; Knösel, Thomas; Yang, Linlin; Zöller, Kristin; Petersen, Iver

    2011-07-01

    Insulin-like growth factor binding protein 7 (IGFBP7) was considered a tumor suppressor gene in lung cancer. However, the mechanism responsible for the downregulation of this gene has not yet been fully understood. In this study, we analyzed the epigenetic inactivation of IGFBP7 expression in human lung cancer. We found that 14 out of 16 lung cancer cell lines showed decreased expression of IGFBP7 compared to control cells by real-time RT-PCR, and 42 out of 90 patients (46.7%) with primary lung tumor exhibited negative staining of IGFBP7 by immunohistochemistry analysis. The IGFBP7 expression could be restored by demethylation agent 5-aza-2'-deoxycytidine (DAC) in 7 cancer cell lines. Methylation status of IGFBP7 was further evaluated by bisulfite sequencing (BS) and methylation-specific-PCR (MSP). It turned out that low expression of IGFBP7 was associated with DNA methylation in lung cancer cell lines and in primary lung tumors (P=0.019). To explore the regulatory role of p53 on IGFBP7, we transfected a wild type p53 expression vector into lung cancer cell lines H1299, H2228, and H82. Forced expression of p53 increased IGFBP7 expression only in H82 harboring no IGFBP7 methylation, while transfection in combination with DAC induced the expression of IGFBP7 in H1299 and H2228, in which IGFBP7 was methylated. Additionally, treatment with p53 inducer adriamycin (ADR) alone or in combination with DAC increased the expression of IGFBP7 in the 3 cell lines. Our data suggest that IGFBP7 is inactivated in lung cancer by DNA hypermethylation in both lung cancer cell lines and primary lung tumors, and IGFBP7 might be regulated by p53 in lung cancer cells. PMID:21095038

  15. Anomalous altered expressions of downstream gene-targets in TP53-miRNA pathways in head and neck cancer.

    Science.gov (United States)

    Mitra, Sanga; Mukherjee, Nupur; Das, Smarajit; Das, Pijush; Panda, Chinmay Kumar; Chakrabarti, Jayprokas

    2014-01-01

    The prevalence of head and neck squamous cell carcinoma, HNSCC, continues to grow. Change in the expression of TP53 in HNSCC affects its downstream miRNAs and their gene targets, anomalously altering the expressions of the five genes, MEIS1, AGTR1, DTL, TYMS and BAK1. These expression alterations follow the repression of TP53 that upregulates miRNA-107, miRNA- 215, miRNA-34 b/c and miRNA-125b, but downregulates miRNA-155. The above five so far unreported genes are the targets of these miRNAs. Meta-analyses of microarray and RNA-Seq data followed by qRT-PCR validation unravel these new ones in HNSCC. The regulatory roles of TP53 on miRNA-155 and miRNA-125b differentiate the expressions of AGTR1 and BAK1in HNSCC vis-à-vis other carcinogenesis. Expression changes alter cell cycle regulation, angiogenic and blood cell formation, and apoptotic modes in affliction. Pathway analyses establish the resulting systems-level functional and mechanistic insights into the etiology of HNSCC.

  16. A novel anticancer therapy that simultaneously targets aberrant p53 and Notch activities in tumors.

    Directory of Open Access Journals (Sweden)

    Yuting Yao

    Full Text Available Notch signaling pathway plays an important role in tumorigenesis by maintaining the activity of self-renewal of cancer stem cells, and therefore, it is hypothesized that interference of Notch signaling may inhibit tumor formation and progression. H101 is a recombinant oncolytic adenovirus that is cytolytic in cells lacking intact p53, but it is unable to eradicate caner stem cells. In this study, we tested a new strategy of tumor gene therapy by combining a Notch1-siRNA with H101 oncolytic adenovirus. In HeLa-S3 tumor cells, the combined therapy blocked the Notch pathway and induced apoptosis in tumors that are p53-inactive. In nude mice bearing xenograft tumors derived from HeLa-S3 cells, the combination of H101/Notch1-siRNA therapies inhibited tumor growth. Moreover, Notch1-siRNA increased Hexon gene expression at both the transcriptional and the translational levels, and promoted H101 replication in tumors, thereby enhancing the oncolytic activity of H101. These data demonstrate the feasibility to combine H101 p53-targted oncolysis and anti-Notch siRNA activities as a novel anti-cancer therapy.

  17. Dual targeted therapy with p53 siRNA and Epigallocatechingallate in a triple negative breast cancer cell model.

    Directory of Open Access Journals (Sweden)

    Cornelia Braicu

    Full Text Available Triple-negative breast cancer (TNBC is a highly aggressive phenotype that is resistant to standard therapy. Thus, the development of alternative therapeutic strategies for TNBC is essential. The purpose of our in vitro study was to evaluate the impact of p53 gene silencing in conjunction with the administration of a natural compound, epigallocatechingallate (EGCG. RT2Profiler PCR Array technology was used to evaluate the impact of dual treatment on the main genes involved in apoptosis in the Hs578T cell culture model of TNBC. Gene expression analysis revealed 28 genes were significantly altered (16 upregulated and 12 downregulated in response to combined p53 siRNA and EGCG treatment. Further analysis revealed that p53 siRNA and EGCG dual therapy leads to the activation of pro-apoptotic genes and the inhibition of pro-survival genes, autophagy, and cell network formation. These results indicate that this dual therapy targets both the apoptotic and angiogenic pathways, which may improve treatment effectiveness for tumors resistant to conventional treatment.

  18. Targeting RING domains of Mdm2-MdmX E3 complex activates apoptotic arm of the p53 pathway in leukemia/lymphoma cells.

    Science.gov (United States)

    Wu, W; Xu, C; Ling, X; Fan, C; Buckley, B P; Chernov, M V; Ellis, L; Li, F; Muñoz, I G; Wang, X

    2015-12-31

    Reactivation of tumor-suppressor p53 for targeted cancer therapy is an attractive strategy for cancers bearing wild-type (WT) p53. Targeting the Mdm2-p53 interface or MdmX ((MDM4), mouse double minute 4)-p53 interface or both has been a focus in the field. However, targeting the E3 ligase activity of Mdm2-MdmX really interesting new gene (RING)-RING interaction as a novel anticancer strategy has never been explored. In this report, we describe the identification and characterization of small molecule inhibitors targeting Mdm2-MdmX RING-RING interaction as a new class of E3 ligase inhibitors. With a fluorescence resonance energy transfer-based E3 activity assay in high-throughput screening of a chemical library, we identified inhibitors (designated as MMRis (Mdm2-MdmX RING domain inhibitors)) that specifically inhibit Mdm2-MdmX E3 ligase activity toward Mdm2 and p53 substrates. MMRi6 and its analog MMRi64 are capable of disrupting Mdm2-MdmX interactions in vitro and activating p53 in cells. In leukemia cells, MMRi64 potently induces downregulation of Mdm2 and MdmX. In contrast to Nutlin3a, MMRi64 only induces the expression of pro-apoptotic gene PUMA (p53 upregulated modulator of apoptosis) with minimal induction of growth-arresting gene p21. Consequently, MMRi64 selectively induces the apoptotic arm of the p53 pathway in leukemia/lymphoma cells. Owing to the distinct mechanisms of action of MMRi64 and Nutlin3a, their combination synergistically induces p53 and apoptosis. Taken together, this study reveals that Mdm2-MdmX has a critical role in apoptotic response of the p53 pathway and MMRi64 may serve as a new pharmacological tool for p53 studies and a platform for cancer drug development.

  19. Forkhead transcription factor FOXF1 is a novel target gene of the p53 family and regulates cancer cell migration and invasiveness.

    Science.gov (United States)

    Tamura, M; Sasaki, Y; Koyama, R; Takeda, K; Idogawa, M; Tokino, T

    2014-10-01

    p53 is an established tumor suppressor that can activate the transcription of multiple target genes. Recent evidence suggests that p53 may contribute to the regulation of cell invasion and migration. In this study, we show that the forkhead box transcription factor FOXF1 is a novel target of the p53 family because FOXF1 is upregulated by p53, TAp73 and TAp63. We show that FOXF1 is induced upon DNA damage in a p53-dependent manner. Furthermore, we identified a response element located within the FOXF1 gene that is responsive to wild-type p53, TAp73β and TAp63γ. The ectopic expression of FOXF1 inhibited cancer cell invasion and migration, whereas the inactivation of FOXF1 stimulated cell invasion and migration. We also show that FOXF1 regulates the transcriptional activity of E-cadherin (CDH1) by acting on its FOXF1 consensus binding site located upstream of the E-cadherin gene. Collectively, our results show that FOXF1 is a p53 family target gene, and our data suggest that FOXF1 and p53 form a portion of a regulatory transcriptional network that appears to have an important role in cancer cell invasion and migration.

  20. RESULTS FROM RECENT SCIENCE AND TECHNOLOGY INVESTIGATIONS TARGETING CHROMIUM IN THE 100D AREA HANFORD SITE WASHINGTON USA

    Energy Technology Data Exchange (ETDEWEB)

    PETERSEN SW; THOMPSON KM; TONKIN MJ

    2009-12-03

    Sodium dichromate was used in Hanford's 100D Area during the reactor operations period of 1950 to 1964 to retard corrosion in the reactor cooling systems. Some of the sodium dichromate was released to the environment by spills and/or leaks from pipelines used to deliver the chemical to water treatment plants in the area. As a result, hexavalent chromium [Cr(VI)] has migrated through the vadose zone to the groundwater and contaminated nearly 1 km{sup 2} of groundwater to above the drinking water standard of 48 {micro}g/L. Three technology tests have recently been completed in this area to characterize the source area of the plumes and evaluate alternative methods to remove Cr(VI) from groundwater. These are (1) refine the source area of the southern plume; (2) test electrocoagulation as an alternative groundwater treatment technology; and (3) test the ability to repair a permeable reactive barrier by injecting micron or nanometer-size zero-valent iron (ZVI). The projects were funded by the US Department of Energy as part of a program to interject new technologies and accelerate active cleanup. Groundwater monitoring over the past 10 years has shown that Cr(VI) concentrations in the southern plume have not significantly diminished, strongly indicating a continuing source. Eleven groundwater wells were installed in 2007 and 2008 near a suspected source area and monitored for Cr(VI) and groundwater levels. Interpretation of these data has led to refinement of the source area location to an area of less than 1 hectare (ha, 2.5 acres). Vadose zone soil samples collected during drilling did not discover significant concentrations of Cr(VI), indicating the source is localized, with a narrow wetted path from the surface to the water table. Electrocoagulation was evaluated through a pilot-scale treatability test. Over 8 million liters of groundwater were treated to Cr(VI) concentrations of {le}20 {micro}g/L. The test determined that this technology has the potential to

  1. p53 activated by AND gate genetic circuit under radiation and hypoxia for targeted cancer gene therapy.

    Science.gov (United States)

    Ding, Miao; Li, Rong; He, Rong; Wang, Xingyong; Yi, Qijian; Wang, Weidong

    2015-09-01

    Radio-activated gene therapy has been developed as a novel therapeutic strategy against cancer; however, expression of therapeutic gene in peritumoral tissues will result in unacceptable toxicity to normal cells. To restrict gene expression in targeted tumor mass, we used hypoxia and radiation tolerance features of tumor cells to develop a synthetic AND gate genetic circuit through connecting radiation sensitivity promoter cArG6 , heat shock response elements SNF1, HSF1 and HSE4 with retroviral vector plxsn. Their construction and dynamic activity process were identified through downstream enhanced green fluorescent protein and wtp53 expression in non-small cell lung cancer A549 cells and in a nude mice model. The result showed that AND gate genetic circuit could be activated by lower required radiation dose (6 Gy) and after activated, AND gate could induce significant apoptosis effects and growth inhibition of cancer cells in vitro and in vivo. The radiation- and hypoxia-activated AND gate genetic circuit, which could lead to more powerful target tumoricidal activity represented a promising strategy for both targeted and effective gene therapy of human lung adenocarcinoma and low dose activation character of the AND gate genetic circuit implied that this model could be further exploited to decrease side-effects of clinical radiation therapy.

  2. Isochoric heating of reduced-mass targets in short pulse laser experiments at 0.53 μm

    Science.gov (United States)

    Baton, Sophie; Audebert, Patrick; Koenig, Michel; Perez, Frederic; Chahid, Makhlad; Rousseaux, Christophe; Gremillet, Laurent; Lefebvre, Erik; Rassuchine, Jenny; Cowan, Tom; Gaillard, Sandrine; Shepperd, Ronnie; Flippo, Kirk

    2008-11-01

    Recent works have shown the possibility to heat isochorically mass limited targets by using the electron refluxing. We report on experiment performed at the 100 TW LULI laser facility dedicated to the study of fast electron transport in multilayer reduced mass targets. The targets were composed of 0.2V/5Cu/5Al μm and varied from 300 to 50 μm in diameter. They were irradiated by a 300 ps laser pulse at 1.057 μm and 0.53 μm that delivered I˜2x10^19 W/cm^2 and I˜10^19 W/cm^2 respectively to form a warm dense plasma. Emission from the rear side was observed using K-alpha spectroscopy and imaging diagnostics. Spectra including the Al and Cu-K-alpha, and Al He-like emissions show changes as a function of total mass. The data obtained from all diagnostics (K-alpha spectroscopy and imagers on the rear side and the transverse side) show a different behavior depending on the incident wavelength.

  3. Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks.

    Science.gov (United States)

    Fischer, Martin; Grossmann, Patrick; Padi, Megha; DeCaprio, James A

    2016-07-27

    Cell cycle (CC) and TP53 regulatory networks are frequently deregulated in cancer. While numerous genome-wide studies of TP53 and CC-regulated genes have been performed, significant variation between studies has made it difficult to assess regulation of any given gene of interest. To overcome the limitation of individual studies, we developed a meta-analysis approach to identify high confidence target genes that reflect their frequency of identification in independent datasets. Gene regulatory networks were generated by comparing differential expression of TP53 and CC-regulated genes with chromatin immunoprecipitation studies for TP53, RB1, E2F, DREAM, B-MYB, FOXM1 and MuvB. RNA-seq data from p21-null cells revealed that gene downregulation by TP53 generally requires p21 (CDKN1A). Genes downregulated by TP53 were also identified as CC genes bound by the DREAM complex. The transcription factors RB, E2F1 and E2F7 bind to a subset of DREAM target genes that function in G1/S of the CC while B-MYB, FOXM1 and MuvB control G2/M gene expression. Our approach yields high confidence ranked target gene maps for TP53, DREAM, MMB-FOXM1 and RB-E2F and enables prediction and distinction of CC regulation. A web-based atlas at www.targetgenereg.org enables assessing the regulation of any human gene of interest. PMID:27280975

  4. Repression of p53-target gene Bbc3/PUMA by MYSM1 is essential for the survival of hematopoietic multipotent progenitors and contributes to stem cell maintenance.

    Science.gov (United States)

    Belle, J I; Petrov, J C; Langlais, D; Robert, F; Cencic, R; Shen, S; Pelletier, J; Gros, P; Nijnik, A

    2016-05-01

    p53 is a central mediator of cellular stress responses, and its precise regulation is essential for the normal progression of hematopoiesis. MYSM1 is an epigenetic regulator essential for the maintenance of hematopoietic stem cell (HSC) function, hematopoietic progenitor survival, and lymphocyte development. We recently demonstrated that all developmental and hematopoietic phenotypes of Mysm1 deficiency are p53-mediated and rescued in the Mysm1(-/-)p53(-/-) mouse model. However, the mechanisms triggering p53 activation in Mysm1(-/-) HSPCs, and the pathways downstream of p53 driving different aspects of the Mysm1(-/-) phenotype remain unknown. Here we show the transcriptional activation of p53 stress responses in Mysm1(-/-) HSPCs. Mechanistically, we find that the MYSM1 protein associates with p53 and colocalizes to promoters of classical p53-target genes Bbc3/PUMA (p53 upregulated modulator of apoptosis) and Cdkn1a/p21. Furthermore, it antagonizes their p53-driven expression by modulating local histone modifications (H3K27ac and H3K4me3) and p53 recruitment. Using double-knockout mouse models, we establish that PUMA, but not p21, is an important mediator of p53-driven Mysm1(-/-) hematopoietic dysfunction. Specifically, Mysm1(-/-)Puma(-/-) mice show full rescue of multipotent progenitor (MPP) viability, partial rescue of HSC quiescence and function, but persistent lymphopenia. Through transcriptome analysis of Mysm1(-/-)Puma(-/-) MPPs, we demonstrate strong upregulation of other p53-induced mediators of apoptosis and cell-cycle arrest. The full viability of Mysm1(-/-)Puma(-/-) MPPs, despite strong upregulation of many other pro-apoptotic mediators, establishes PUMA as the essential non-redundant effector of p53-induced MPP apoptosis. Furthermore, we identify potential mediators of p53-dependent but PUMA-independent Mysm1(-/-)hematopoietic deficiency phenotypes. Overall, our study provides novel insight into the cell-type-specific roles of p53 and its downstream

  5. Conserved regulation of p53 network dosage by microRNA-125b occurs through evolving miRNA-target gene pairs.

    Directory of Open Access Journals (Sweden)

    Minh T N Le

    2011-09-01

    Full Text Available MicroRNAs regulate networks of genes to orchestrate cellular functions. MiR-125b, the vertebrate homologue of the Caenorhabditis elegans microRNA lin-4, has been implicated in the regulation of neural and hematopoietic stem cell homeostasis, analogous to how lin-4 regulates stem cells in C. elegans. Depending on the cell context, miR-125b has been proposed to regulate both apoptosis and proliferation. Because the p53 network is a central regulator of both apoptosis and proliferation, the dual roles of miR-125b raise the question of what genes in the p53 network might be regulated by miR-125b. By using a gain- and loss-of-function screen for miR-125b targets in humans, mice, and zebrafish and by validating these targets with the luciferase assay and a novel miRNA pull-down assay, we demonstrate that miR-125b directly represses 20 novel targets in the p53 network. These targets include both apoptosis regulators like Bak1, Igfbp3, Itch, Puma, Prkra, Tp53inp1, Tp53, Zac1, and also cell-cycle regulators like cyclin C, Cdc25c, Cdkn2c, Edn1, Ppp1ca, Sel1l, in the p53 network. We found that, although each miRNA-target pair was seldom conserved, miR-125b regulation of the p53 pathway is conserved at the network level. Our results lead us to propose that miR-125b buffers and fine-tunes p53 network activity by regulating the dose of both proliferative and apoptotic regulators, with implications for tissue stem cell homeostasis and oncogenesis.

  6. Potential therapeutic targets for oral cancer: ADM, TP53, EGFR, LYN, CTLA4, SKIL, CTGF, CD70.

    Directory of Open Access Journals (Sweden)

    Saurabh Bundela

    Full Text Available In India, oral cancer has consistently ranked among top three causes of cancer-related deaths, and it has emerged as a top cause for the cancer-related deaths among men. Lack of effective therapeutic options is one of the main challenges in clinical management of oral cancer patients. We interrogated large pool of samples from oral cancer gene expression studies to identify potential therapeutic targets that are involved in multiple cancer hallmark events. Therapeutic strategies directed towards such targets can be expected to effectively control cancer cells. Datasets from different gene expression studies were integrated by removing batch-effects and was used for downstream analyses, including differential expression analysis. Dependency network analysis was done to identify genes that undergo marked topological changes in oral cancer samples when compared with control samples. Causal reasoning analysis was carried out to identify significant hypotheses, which can explain gene expression profiles observed in oral cancer samples. Text-mining based approach was used to detect cancer hallmarks associated with genes significantly expressed in oral cancer. In all, 2365 genes were detected to be differentially expressed genes, which includes some of the highly differentially expressed genes like matrix metalloproteinases (MMP-1/3/10/13, chemokine (C-X-C motif ligands (IL8, CXCL-10/-11, PTHLH, SERPINE1, NELL2, S100A7A, MAL, CRNN, TGM3, CLCA4, keratins (KRT-3/4/13/76/78, SERPINB11 and serine peptidase inhibitors (SPINK-5/7. XIST, TCEAL2, NRAS and FGFR2 are some of the important genes detected by dependency and causal network analysis. Literature mining analysis annotated 1014 genes, out of which 841 genes were statistically significantly annotated. The integration of output of various analyses, resulted in the list of potential therapeutic targets for oral cancer, which included targets such as ADM, TP53, EGFR, LYN, CTLA4, SKIL, CTGF and CD70.

  7. Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks

    OpenAIRE

    Fischer, Martin; Grossmann, Patrick; Padi, Megha; DeCaprio, James A.

    2016-01-01

    Cell cycle (CC) and TP53 regulatory networks are frequently deregulated in cancer. While numerous genome-wide studies of TP53 and CC-regulated genes have been performed, significant variation between studies has made it difficult to assess regulation of any given gene of interest. To overcome the limitation of individual studies, we developed a meta-analysis approach to identify high confidence target genes that reflect their frequency of identification in independent datasets. Gene regulator...

  8. 筛选 p53靶向药物的细胞模型的构建%Establishing reporter Cell lines as a model system for p 53-targeted drug screening

    Institute of Scientific and Technical Information of China (English)

    胡琳珊; 张海波; 童英; 张渝君

    2013-01-01

    为了筛选可以恢复肿瘤细胞中p53功能的小分子,作者用表达野生型p53的人类直肠癌细胞HCT116建立了一株能够应答激活p53信号通路的荧光素酶报告基因的稳定细胞系,同时用表达野生型p53的人类骨肉瘤细胞U2-O S建立了一株能够应答激活p53信号通路的mCherry红色荧光蛋白报告基因的稳定细胞系。为了检测筛选p53靶向药物的有效性,利用三种已知的以p53为靶点的小分子药物(cisplatin ,doxorubicin以及Nutlin-3)处理这两种稳定细胞系,结果显示 p53信号通路在这两个稳定细胞系中均能够被激活。为了探索小分子RN A作为恢复p53功能的靶标药物,并进一步验证这两种细胞模型用于药物筛选的可行性,分别检测了MDM2和MDMX的5个不同shRNA 。通过比较HCT116稳定细胞的荧光素酶活性和U2-OS稳定细胞中荧光蛋白的荧光强度,我们筛选出了有效沉默MDM2或MDMX的shRNA 。数据表明,这两种细胞模型不仅可用作筛选激活p53的小分子化合物的平台,而且可用于筛选激活p53信号通路的小分子RNA 。%To screen for small molecules that could restore the functions of p53 in tumor cells ,a HCT116 reporter cell line (derived from human colorectal carcinoma carrying the wild type p53 gene) stably expressing luciferase under the control of promoter that containing a p53-responsive element , and a U2-OS reporter cell line (derived from human osteosarcoma carrying the wild type p53 gene) stably expressing mCherry red fluorescent protein under the control of promoter that also containing a p53-responsive element have been established . To validate these two stable reporter cell lines for p53-targeted drug screening , three known p53-targeted small molecules , Cisplatin , Doxorubicin and Nutlin-3 have been used to examine these cells ,the results shown that p53 signal pathway was able to be activated in both stable reporter cell lines . To exploring

  9. Expression of the p53 target Wig-1 is associated with HPV status and patient survival in cervical carcinoma.

    Directory of Open Access Journals (Sweden)

    Li-Di Xu

    Full Text Available The p53 target gene WIG-1 (ZMAT3 is located in chromosomal region 3q26, that is frequently amplified in human tumors, including cervical cancer. We have examined the status of WIG-1 and the encoded Wig-1 protein in cervical carcinoma cell lines and tumor tissue samples. Our analysis of eight cervical cancer lines (Ca Ski, ME-180, MS751, SiHa, SW756, C-4I, C-33A, and HT-3 by spectral karyotype, comparative genomic hybridization and Southern blotting revealed WIG-1 is not the primary target for chromosome 3 gains. However, WIG-1/Wig-1 were readily expressed and WIG-1 mRNA expression was higher in the two HPV-negative cervical cell lines (C33-A, HT-3 than in HPV-positive lines. We then assessed Wig-1 expression by immunohistochemistry in 38 cervical tumor samples. We found higher nuclear Wig-1 expression levels in HPV-negative compared to HPV positive cases (p = 0.002 and in adenocarcinomas as compared to squamous cell lesions (p<0.0001. Cases with moderate nuclear Wig-1 staining and positive cytoplasmic Wig-1 staining showed longer survival than patients with strong nuclear and negative cytoplasmic staining (p = 0.042. Nuclear Wig-1 expression levels were positively associated with age at diagnosis (p = 0.023 and histologic grade (p = 0.034. These results are consistent with a growth-promoting and/or anti-cell death function of nuclear Wig-1 and suggest that Wig-1 expression can serve as a prognostic marker in cervical carcinoma.

  10. Hexavalent chromium targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent caspase-3 activation in L-02 hepatocytes.

    Science.gov (United States)

    Xiao, Fang; Li, Yanhong; Dai, Lu; Deng, Yuanyuan; Zou, Yue; Li, Peng; Yang, Yuan; Zhong, Caigao

    2012-09-01

    Hexavalent chromium [Cr(VI)], which is used for various industrial applications, such as leather tanning and chroming, can cause a number of human diseases including inflammation and cancer. Cr(VI) exposure leads to severe damage to the liver, but the mechanisms involved in Cr(VI)-mediated toxicity in the liver are unclear. The present study provides evidence that Cr(VI) enhances reactive oxygen species (ROS) accumulation by inhibiting the mitochondrial respiratory chain complex (MRCC) I. Cr(VI) did not affect the expression levels of antioxidative proteins such as superoxide dismutase (SOD), catalase and thioredoxin (Trx), indicating that the antioxidative system was not involved in Cr(VI)-induced ROS accumulation. We found that ROS mediated caspase-3 activation partially depends on the downregulation of the heat shock protein (HSP) 70 and 90. In order to confirm our hypothesis that ROS plays a key role in Cr(VI)-mediated cytotoxicity, we used N-acetylcysteine (NAC) to inhibit the accumulation of ROS. NAC successfully blocked the inhibition of HSP70 and HSP90 as well as the activation of caspase-3, suggesting that ROS is essential in Cr(VI)-induced caspase-3 activation. By applying different MRCC substrates as electron donors, we also confirmed that Cr(VI) could accept the electrons leaked from MRCC I and the reduction occurs at MRCC I. In conclusion, the present study demonstrates that Cr(VI) induces ROS-dependent caspase-3 activation by inhibiting MRCC I activity, and MRCC I has been identified as a new target and a new mechanism for the apoptosis-inducing activity displayed by Cr(VI). PMID:22710416

  11. Combined MYC and P53 Defects Emerge at Medulloblastoma Relapse and Define Rapidly Progressive, Therapeutically Targetable Disease

    OpenAIRE

    Hill, Rebecca M.; Kuijper, Sanne; Lindsey, Janet C.; Petrie, Kevin; Schwalbe, Ed C.; Barker, Karen; Boult, Jessica K. R.; Williamson, Daniel; Ahmad, Zai; Hallsworth, Albert; Ryan, Sarra L.; Poon, Evon; Simon P Robinson; Ruddle, Ruth; Raynaud, Florence I.

    2015-01-01

    Summary We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 functi...

  12. Targeting of p300/CREB Binding Protein Coactivators by Simian Virus 40 Is Mediated through p53

    OpenAIRE

    Borger, Darrell R.; DeCaprio, James A.

    2006-01-01

    The primary transforming functions of simian virus 40 large T antigen (SV40 LT) are conferred primarily through the binding and inactivation of p53 and the retinoblastoma family members. Normal p53 function requires an association with the CREB binding protein (CBP)/p300 coactivators, and a ternary complex containing SV40 LT, p53, and CBP/p300 has been identified previously. In this report, we have evaluated a secondary function of p53 bound to the SV40 LT complex in mediating the binding of ...

  13. ARGUS disk-target experiments at 1.06 μm, 0.53 μm, 0.35 μm

    International Nuclear Information System (INIS)

    We report on ARGUS wavelength scaling experiments on disk targets at 1.06 μm, 0.53 μm, and 0.35 μm. Measurements were made of absorption, stimulated Brillouin and Raman scattering, and 3/2 harmonic light

  14. Antifolates targeting purine synthesis allow entry of tumor cells into S phase regardless of p53 function.

    Science.gov (United States)

    Bronder, Julie L; Moran, Richard G

    2002-09-15

    The class of folate antimetabolites typified by (6R)-dideazatetrahydrofolate (lometrexol, DDATHF) are specific inhibitors of de novo purine synthesis because of potent inhibition of glycinamide ribonucleotide formyltransferase (GART) but do not induce detectable levels of DNA strand breaks. As such, they are a test case of the concept that ribonucleotide depletion can be sensed by p53, resulting in a G(1) cell cycle block. The GART inhibitors have been proposed previously to be cytotoxic in tumor cells lacking p53 function but only cytostatic in p53 wild-type tumor cells. We have investigated this concept. Cell cycle progression into and through S phase was slowed by DDATHF, but both p53 +/+ and -/- human colon carcinoma cells entered and completed one S phase in the presence of drug. This inability of p53 to initiate a G(1) arrest after DDATHF treatment was mirrored by an independence of the cytotoxicity of DDATHF on p53 function. We conclude that carcinoma cells are killed equally well by DDATHF and related compounds whether or not the p53 pathway is intact and that the utility of GART inhibitors would not be limited to p53-negative tumors. PMID:12234990

  15. A novel drug discovery strategy: Mechanistic investigation of an enantiomeric antitumor agent targeting dual p53 and NF-κB pathways

    Science.gov (United States)

    Shin, Woo Shik; Wu, Yuelin; Li, Jin; Yao, Jianzhong; Dong, Guoqiang; Zhang, Wen; Sham, Yuk Yin; Miao, Zhenyuan; Zhang, Wannian

    2014-01-01

    The p53 and nuclear factor κB (NF-κB) pathways play crucial roles in human cancer development. Simultaneous targeting of both pathways is an attractive therapeutic strategy against cancer. In this study, we report an antitumor molecule that bears a pyrrolo[3,4-c]pyrazole scaffold and functions as an enantiomeric inhibitor against both the p53-MDM2 interaction and the NF-κB activation. It is a first-in-class enantiomeric inhibitor with dual efficacy for cancer therapy. Synergistic effect was observed in vitro and in vivo. Docking and molecular dynamics simulation studies further provided insights into the nature of stereoselectivity. PMID:25350970

  16. Mortalin-p53 interaction in cancer cells is stress dependent and constitutes a selective target for cancer therapy

    OpenAIRE

    Lu, W-J; Lee, N. P.; Kaul, S C; Lan, F.; Poon, R T P; Wadhwa, R; Luk, J M

    2011-01-01

    Stress protein mortalin is a multifunctional protein and is highly expressed in cancers. It has been shown to interact with tumor suppressor protein-p53 (both wild and mutant types) and inactivates its transcriptional activation and apoptotic functions in cancer cells. In the present study, we found that, unlike most of the cancer cells, HepG2 hepatoma lacked mortalin-p53 interaction. We demonstrate that the mortalin-p53 interaction exists in cancer cells that are either physiologically stres...

  17. Chromium in diet

    Science.gov (United States)

    The best source of chromium is brewer's yeast. However, many people do not use brewer's yeast because it causes bloating ( abdominal distention ) and nausea . Other good sources of chromium include ...

  18. Redox-responsive targeted gelatin nanoparticles for delivery of combination wt-p53 expressing plasmid DNA and gemcitabine in the treatment of pancreatic cancer

    International Nuclear Information System (INIS)

    Pancreatic adenocarcinoma is one of the most dreaded cancers with very low survival rate and poor prognosis to the existing frontline chemotherapeutic drugs. Gene therapy in combination with a cytotoxic agent could be a promising approach to circumvent the limitations of previously attempted therapeutic interventions. We have developed a redox-responsive thiolated gelatin based nanoparticle system that efficiently delivers its payload in the presence of glutathione-mediated reducing intra-cellular environment and could be successfully used for site-specific wt-p53 expressing plasmid DNA as well as gemcitabine delivery by targeting epidermal growth factor receptor (EGFR). Efficacy studies were performed in subcutaneous human adenocarcinoma bearing SCID beige mice along with molecular level p53 plasmid and apoptotic marker expression by PCR and western blot for all study groups. Efficacy studies demonstrate an improved in vivo targeting efficiency resulting in increased transfection efficiency and tumor growth suppression. In all the treatment groups, the targeted nanoparticles showed better anti-tumor activity than their non-targeted as well as non-encapsulated, naked therapeutic agent counterparts (50.1, 61.7 and 77.3% tumor regression by p53 plasmid alone, gemcitabine alone and in combination respectively). Molecular analysis revealed a higher mRNA expression of transfected p53 gene, its corresponding protein and that the tumor cell death in all treatment groups was due to the induction of apoptotic pathways. Gene/drug combination treatment significantly improves the therapeutic performance of the delivery system compared to the gene or drug alone treated groups. Anti-tumor activity of the thiolated gelatin loaded wt-p53 plasmid or gemcitabine-based therapy was attributed to their ability to induce cell apoptosis, which was confirmed by a marked increase in mRNA level of proapoptotic transcription factors, as well as, protein apoptotic biomarker expression and

  19. Chromium and Genomic Stability

    OpenAIRE

    Wise, Sandra S.; Wise, John Pierce

    2011-01-01

    Many metals serve as micronutrients which protect against genomic instability. Chromium is most abundant in its trivalent and hexavalent forms. Trivalent chromium has historically been considered an essential element, though recent data indicate that while it can have pharmacological effects and value, it is not essential. There are no data indicating that trivalent chromium promotes genomic stability and, instead may promote genomic instability. Hexavalent chromium is widely accepted as high...

  20. miR-214 promotes apoptosis and sensitizes breast cancer cells to doxorubicin by targeting the RFWD2-p53 cascade.

    Science.gov (United States)

    Zhang, Jiaxuan; Su, Beibei; Gong, Chen; Xi, Qingsongg; Chao, Tengfei

    2016-09-01

    miR-214 is involved in numerous physiological and pathological processes including tumorigenesis. However, the function of miR-214 in the development and treatment of breast cancer remains elusive. In this study, we report that miR-214 is strikingly down-regulated in breast cancer cell lines and clinical samples, particularly, in the doxorubicin resistant tumor tissues. Remarkably, restoration of miR-214 expression induces apoptosis and sensitizes the MCF7 cells sustaining wild-type p53, but not the p53 null MDA-MB-157 cells, to doxorubicin. Furthermore, we reveal that miR-214 directly down-regulates the expression of RFWD2, also known as COP1, an E3 ligase targeting the tumor suppressor p53 for proteasomal degradation. In addition, RFWD2 protein levels are reversely correlated with miR-214 expression levels in breast cancer tissues. Moreover, ectopic expression of RFWD2 markedly abolishes miR-214-triggered apoptosis of MCF7 cells. In conclusion, miR-214 functions as a tumor suppressor by regulating the RFWD2-p53 cascade, thus delivery of miR-214 analogs could be a potential adjunct therapy in breast cancer harboring wild type p53. PMID:27422604

  1. MicroRNA-128-2 targets the transcriptional repressor E2F5 enhancing mutant p53 gain of function

    Science.gov (United States)

    Donzelli, S; Fontemaggi, G; Fazi, F; Di Agostino, S; Padula, F; Biagioni, F; Muti, P; Strano, S; Blandino, G

    2012-01-01

    p53 mutations have profound effects on non-small-cell lung cancer (NSCLC) resistance to chemotherapeutic treatments. Mutant p53 proteins are usually expressed at high levels in tumors, where they exert oncogenic functions. Here we show that p53R175H, a hotspot p53 mutant, induces microRNA (miRNA)-128-2 expression. Mutant p53 binds to the putative promoter of miR128-2 host gene, ARPP21, determining a concomitant induction of ARPP21 mRNA and miR-128-2. miR-128-2 expression in lung cancer cells inhibits apoptosis and confers increased resistance to cisplatin, doxorubicin and 5-fluorouracyl treatments. At the molecular level, miR-128-2 post-transcriptionally targets E2F5 and leads to the abrogation of its repressive activity on p21waf1 transcription. p21waf1 protein localizes to the cytoplasmic compartment, where it exerts an anti-apoptotic effect by preventing pro-caspase-3 cleavage. This study emphasizes miRNA-128-2 role as a master regulator in NSCLC chemoresistance. PMID:22193543

  2. p300 and p53 levels determine activation of HIF-1 downstream targets in invasive breast cancer

    NARCIS (Netherlands)

    Vleugel, M.M.; Shvarts, D.; Wall, E. van der; Diest, P.J. van

    2006-01-01

    In previous studies, we noted that overexpression of hypoxia-inducible factor (HIF)–1a in breast cancer, especially the diffuse form, does not always lead to functional activation of its downstream genes. Transcriptional activity of HIF-1 may be repressed by p53 through competition for transcription

  3. Application of CellDesigner to the Selection of Anticancer Drug Targets: Test Case using P53

    OpenAIRE

    Isea, Raul; Hoebeke, Johan; Mayo, Rafael; Alvarez, Fernando; Holmes, David S.

    2013-01-01

    Cancer is a disease involving many genes, consequently it has been difficult to design anticancer drugs that are efficacious over a broad range of cancers. The robustness of cellular responses to gene knockout and the need to reduce undesirable side effects also contribute to the problem of effective anti-cancer drug design. To promote the successful selection of drug targets, each potential target should be subjected to a systems biology scrutiny to locate effective and specific targets whil...

  4. Chromium Enrichment on P11 Ferritic Steel by Pack Cementation

    Directory of Open Access Journals (Sweden)

    Fauzi F. A.

    2016-01-01

    Full Text Available The future thermal power plant is expected to operate at higher temperature to improve its efficiency and to reduce greenhouse gas emission. This target requires better corrosion properties of ferritic steels, which commonly used as materials for superheater and reheater of boiler tubes. In this work, chromium enrichment on the surface of ferritic steel is studied. The deposited chromium is expected to become a reservoir for the formation of chromia protective layer. Chromium was deposited on the substrate of steel by pack cementation process for two hours at the temperature of 850ºC, 950ºC and 1050ºC, respectively. XRD analysis indicated that chromium was successfully deposited at all temperatures. Somehow, SEM cross sectional image showed that continuous layer of chromium was not continuously formed at 850oC. Therefore, this research clarify that chromium enrichment by pack cementation may be conducted at the temperature above 950°C.

  5. Targeting p53-MDM2 negative feedback loops for treatment of cancer%针对p53-鼠双微体基因负反馈环的肿瘤治疗

    Institute of Scientific and Technical Information of China (English)

    吴学元; 马巍

    2009-01-01

    MDM2 controls p53 function through inhibiting p53-mediated transcriptional activity and promoting p53 degradation.Over-expression of MDM2 inactivates p53 and induces wide-type p53 cells malignant transformation.So inhibition of the p53-MDM2 interaction with synthetic molecules should therefore lead to both the nuclear accumulation and the activation of p53 followed by the death of the tumor cells from apoptosis.Inhibitors of the p53-MDM2 interaction might be attractive new anticancer agents that could be used to activate wild-type p53 in tumors.%鼠双微体基因(MDM2)通过抑制p53介导的转录活性和促进p53降解来控制p53的功能.MDM2过度表达引起p53失活,导致p53野生细胞恶性转化.人工合成抑制p53-MDM2蛋白复合体相互作用的小分子可促使p53核内积聚、活化p53,从而诱导肿瘤细胞的死亡.针对p53-MDM2相互作用的抑制剂可成为治疗p53野生型肿瘤系的新型抗癌药物.

  6. Astemizole-Histamine induces Beclin-1-independent autophagy by targeting p53-dependent crosstalk between autophagy and apoptosis.

    Science.gov (United States)

    Jakhar, Rekha; Paul, Souren; Bhardwaj, Monika; Kang, Sun Chul

    2016-03-01

    Apoptosis and autophagy are genetically regulated, evolutionarily conserved processes that can jointly seal cancer cell fates, and numerous death stimuli are capable of activating either pathway. Although crosstalk between apoptosis and autophagy is quite complex and sometimes contradictory, it remains a key factor determining the outcomes of death-related pathologies such as cancer. In the present study, exposure of MCF-7 breast cancer cells to HIS and the H1 receptor antagonist AST both alone and together with HIS (AST-HIS) led to generation of intracellular ROS, which induced massive cellular vacuolization through dilation of the ER and mitochondria. Consequently, apoptosis by Bax translocation, cytochrome c release, and caspase activation were triggered. In addition, AST-HIS caused ER stress-induced autophagy in MCF-7 cells, as evidenced by an increased LC3-II/LC3-I ratio, with surprisingly no changes in Beclin-1 expression. Non-canonical autophagy was induced via p53 phosphorylation, which increased p53-p62 interactions to enhance Beclin-1-independent autophagy as evidenced by immunocytochemistry and immunoprecipitation. In the absence of Beclin-1, enhanced autophagy further activated apoptosis through caspase induction. In conclusion, these findings indicate that AST-HIS-induced apoptosis and autophagy can be regulated by ROS-mediated signaling pathways. PMID:26739061

  7. Characterization of dual PTEN and p53-targeting microRNAs identifies microRNA-638/Dnm2 as a two-hit oncogenic locus

    OpenAIRE

    Yvonne Tay; Shen Mynn Tan; Florian A. Karreth; Judy Lieberman; Pier Paolo Pandolfi

    2014-01-01

    Tumor suppressor genes (TSGs) are often concomitantly lost or mutated in human cancers and have been shown to act synergistically to promote tumorigenesis. In addition to genomic alterations, posttranscriptional regulation by microRNAs (miRNAs) represents another mechanism by which TSG expression is dysregulated in cancers. Although miRNAs that target critical TSGs such as PTEN or p53 have been identified, little is known about miRNAs that concomitantly regulate both these key TSGs. In this s...

  8. Metabonomics applied in exploring the antitumour mechanism of physapubenolide on hepatocellular carcinoma cells by targeting glycolysis through the Akt-p53 pathway

    Science.gov (United States)

    Ma, Ting; Fan, Bo-Yi; Zhang, Chao; Zhao, Hui-Jun; Han, Chao; Gao, Cai-Yun; Luo, Jian-Guang; Kong, Ling-Yi

    2016-01-01

    Metabolomics can be used to identify potential markers and discover new targets for future therapeutic interventions. Here, we developed a novel application of the metabonomics method based on gas chromatography-mass spectrometry (GC/MS) analysis and principal component analysis (PCA) for rapidly exploring the anticancer mechanism of physapubenolide (PB), a cytotoxic withanolide isolated from Physalis species. PB inhibited the proliferation of hepatocellular carcinoma cells in vitro and in vivo, accompanied by apoptosis-related biochemical events, including the cleavage of caspase-3/7/9 and PARP. Metabolic profiling analysis revealed that PB disturbed the metabolic pattern and significantly decreased lactate production. This suggests that the suppression of glycolysis plays an important role in the anti-tumour effects induced by PB, which is further supported by the decreased expression of glycolysis-related genes and proteins. Furthermore, the increased level of p53 and decreased expression of p-Akt were observed, and the attenuated glycolysis and enhanced apoptosis were reversed in the presence of Akt cDNA or p53 siRNA. These results confirm that PB exhibits anti-cancer activities through the Akt-p53 pathway. Our study not only reports for the first time the anti-tumour mechanism of PB, but also suggests that PB is a promising therapeutic agent for use in cancer treatments and that metabolomic approaches provide a new strategy to effectively explore the molecular mechanisms of promising anticancer compounds. PMID:27416811

  9. CDK1 Inhibition Targets the p53-NOXA-MCL1 Axis, Selectively Kills Embryonic Stem Cells, and Prevents Teratoma Formation

    Directory of Open Access Journals (Sweden)

    Noelle E. Huskey

    2015-03-01

    Full Text Available Embryonic stem cells (ESCs have adopted an accelerated cell-cycle program with shortened gap phases and precocious expression of cell-cycle regulatory proteins, including cyclins and cyclin-dependent kinases (CDKs. We examined the effect of CDK inhibition on the pathways regulating proliferation and survival of ESCs. We found that inhibiting cyclin-dependent kinase 1 (CDK1 leads to activation of the DNA damage response, nuclear p53 stabilization, activation of a subset of p53 target genes including NOXA, and negative regulation of the anti-apoptotic protein MCL1 in human and mouse ESCs, but not differentiated cells. We demonstrate that MCL1 is highly expressed in ESCs and loss of MCL1 leads to ESC death. Finally, we show that clinically relevant CDK1 inhibitors prevent formation of ESC-derived tumors and induce necrosis in established ESC-derived tumors. Our data demonstrate that ES cells are uniquely sensitive to CDK1 inhibition via a p53/NOXA/MCL1 pathway.

  10. Substoichiometric extraction of chromium

    International Nuclear Information System (INIS)

    Substoichiometric extraction of chromium with tetraphenylarsonium chloride (TPACl), tri-n-octylamine (TNOA), diethylammonium diethyldithiocarbamate (DDDC) and ammonium pyrrolidinedithiocarbamate (APDC) was examined in detail. Chromium can be extracted substoichiometrically in a pH range, which is 1.1-2.6 for the TPACl compound, 0.6-2.3 for the TNOA compound, 5.1-6.4 for the DDDC chelate and 3.9-4.9 for the APDC chelate. Chromium in high-purity calcium carbonate, Orchard Leaves (NBS SRM-1571) and Brewers Yeast (NBS SRM-1569) was determined by neutron activation analysis combined with substoichiometric extraction by DDDC and APDC. The values of 2.0+-0.02 ppm and 2.6+-0.2 ppm were obtained for Brewers Yeast and Orchard Leaves, respectively. These values were in good agreement with those reported by NBS. The reaction mechanism and the reaction ratio between hexavalent chromium and dithiocarbamate are also discussed. (author)

  11. The carcinogenicity of chromium

    OpenAIRE

    Norseth, Tor

    1981-01-01

    The carcinogenicity of chromium compounds is reviewed with specific attention to the gaps in knowledge for risk estimation and research needs. The most important problems at present are whether trivalent chromium compounds cause cancer, and whether there is a difference in cancer causing effects between the soluble and the slightly soluble hexavalent compounds in the practical exposure situation. Dose estimates for risk estimation based on epidemiological investigations are also lacking. Pres...

  12. Tumor protein 53-induced nuclear protein 1 (TP53INP1 enhances p53 function and represses tumorigenesis

    Directory of Open Access Journals (Sweden)

    Jeyran eShahbazi

    2013-05-01

    Full Text Available Tumor protein 53-induced nuclear protein 1 (TP53INP1 is a stress-induced p53 target gene whose expression is modulated by transcription factors such as p53, p73 and E2F1. TP53INP1 gene encodes two isoforms of TP53INP1 proteins, TP53INP1α and TP53INP1β, both of which appear to be key elements in p53 function. When associated with homeodomain-interacting protein kinase-2 (HIPK2, TP53INP1 phosphorylates p53 protein at Serine 46, enhances p53 protein stability and its transcriptional activity, leading to transcriptional activation of p53 target genes such as p21, PIG-3 and MDM2, cell growth arrest and apoptosis upon DNA damage stress. The anti-proliferative and pro-apoptotic activities of TP53INP1 indicate that TP53INP1 has an important role in cellular homeostasis and DNA damage response. Deficiency in TP53INP1 expression results in increased tumorigenesis; while TP53INP1 expression is repressed during early stages of cancer by factors such as miR-155. This review aims to summarize the roles of TP53INP1 in blocking tumor progression through p53-dependant and p53-independent pathways, as well as the elements which repress TP53INP1 expression, hence highlighting its potential as a therapeutic target in cancer treatment.

  13. Interventional targeting administration of Ad-p53 combined with ultrasound irradiation in rabbit models of hepatic VX2 tumors%介入导入Ad-p53基因联合超声辐照治疗兔VX2肝癌

    Institute of Scientific and Technical Information of China (English)

    齐劲松; 杨瑞民; 赵鹏; 张铭秋; 崔红凯

    2013-01-01

    Objective To observe the effect of interventional targeting administration of Ad-p53 combined with ultrasound irradiation in rabbit models of hepatic VX2 tumors, as well as its impact on VEGF and MMP2. Methods Forty-two Chinchilla rabbits were collected and VX2 cancer cells were injected into the left lobe of liver on the observation in rabbits. The growth of cancer was monitored by ultrasound. Thirty rabbit models were successfully made and divided into 3 groups (each n=10) randomly. Fourteen days after transplantation of cancer cells, Ad-p53 was administrated through hepatic artery (in Ad-p53 group) or combined with ultrasound wave irradiation (in Ad-p53 + US group), while the same amount of saline was given for rabbits in control group. Three days later, the tumor size was observed with ultrasound, and then all rabbits were sacrificed, the serum VEGF level was measured by ELISA, the hepatic tissue expression of p53, MMP2 and VEGF were detected respectively by immunohistochemistry, and expression level of wild type p53 was measured using Western blot. Results No difference of tumor size was found between 3 groups before therapy. All tumor sizes increased, but the tumors in Ad-p53 + US group were relatively smaller. The efficiency of Ad-p53 transfection was improved in Ad-p53 group compared with control group, which was the highest in Ad-p53 + US group. Furthermore, the serum VEGF level decreased in Ad-p53 + US group, so did the expression of MMP2 and VEGF in Ad-p53 group and Ad-p53 + US group, more obviously in Ad-p53 + US group. Conclusion Ad-p53 can suppress the growth of hepatic VX2 tumors in rabbit models. The therapeutic efficacy of Ad-p53 can be improved by interventional targeting administration combining with ultrasound irradiation.%目的 探讨介入导向下联合超声辐照对兔VX2肝癌模型Ad-p53转染效率及该基因对VEGF、MMP2的影响.方法 青紫蓝兔42只,直视下手术,将VX2肿瘤细胞种植于肝左叶,以超声检测

  14. Obtaining decorative chromium plating from trivalent chromium solutions

    OpenAIRE

    Óscar Javier Suárez García

    2010-01-01

    The present work was aimed at a qualitative evaluation, in the laboratory, of different alternatives for assembling and operating a trivalent chromium bath for decorative chromium plating. Different chromium concentration solutions and different complexing agents were used. The initial result of this analysis was that chloride, formate and acetate solutions produced the best results. Solution preparation conditions were evaluated: temperature, chromium III complex formation time and also ...

  15. MicroRNA-34a affects chondrocyte apoptosis and proliferation by targeting the SIRT1/p53 signaling pathway during the pathogenesis of osteoarthritis.

    Science.gov (United States)

    Yan, Shiju; Wang, Meng; Zhao, Jian; Zhang, Hongtao; Zhou, Chengpei; Jin, Lei; Zhang, Yinglong; Qiu, Xiuchun; Ma, Baoan; Fan, Qingyu

    2016-07-01

    Osteoarthritis (OA) is the most prevalent degenerative joint disease with multifactorial etiology caused by risk factors such as ageing, obesity and trauma. Previously, it was reported that the inhibition of microRNA-34a (miR-34a) may reduce rat chondrocyte apoptosis induced by IL-1β, whereas the molecular mechanism and the role of miR-34a in human chondrocyte as well as in OA progression remains to be determined. In the current study, using MTT, luciferase reporter assays and western blot analysis we identified that miR-34a was upregulated while silent information regulator 1 (SIRT1) was inhibited in chondrocytes from 12 OA patients compared with healthy chondrocytes from 10 trauma amputees. Overexpression of miR-34a promoted apoptosis and inhibited cell proliferation in human chondrocytes. Transfection with miR-34a mimic inhibited SIRT1 expression, which attenuated the deacetylation of p53, leading to the upregulation of Bax and downregulation of Bcl-2. Furthermore, results from the western blot analysis and luciferase reporter assay demonstrated that SIRT1 was directly regulated by miR-34a in human chondrocytes. A rat model of OA was induced through anterior cruciate ligament transection and medial meniscus resection (ACLT+MMx). The results showed that the intra‑articular injection of lentiviral vector encoding anti-miR‑34a sequence effectively ameliorated the progression of OA. The results suggest that miR-34a has a crucial role in the pathogenesis of OA through direct regulation of the SIRT1/p53 signaling pathway and serves as a potential therapeutic target of OA.

  16. HPV E6/p53 mediated down-regulation of miR-34a inhibits Warburg effect through targeting LDHA in cervical cancer.

    Science.gov (United States)

    Zhang, Rong; Su, Jing; Xue, Song-Lin; Yang, Hui; Ju, Li-Li; Ji, Ying; Wu, Kai-Hua; Zhang, Yan-Wei; Zhang, Ye-Xin; Hu, Jian-Fang; Yu, Min-Min

    2016-01-01

    MicroRNAs (miRNA) play crucial roles in regulating cell proliferation, differentiation and developmental timing. Aberrantly expressed miRNAs have recently emerged as key regulators of metabolism. However, little is known about its role in tumor metabolism of cervical cancer. In this study, we determined the oncogenic effects of miRNAs on Warburg effect, a metabolic phenotype that allows cancer cells to utilize glucose even under aerobic conditions. A gain-of-function study was performed in 12 down-regulated miRNAs that frequently reported in cervical cancer. We found that miR-34a plays a suppressive role in Warburg effect as evidenced by decreased lactate production and glucose consumption. Knockdown of oncoprotein E6 expression of human papillomavirus in SiHa and HeLa cells by siRNAs lead to an increased protein level of p53, decreased level of miR-34a, as well as reduced Warburg effect. Subsequently, lactate dehydrogenase A (LDHA), which catalyzes the last key step in glycolysis, was identified as a direct target of miR-34a. Silencing of LDHA or introduction of miR-34a significantly attenuated colony formation ability and invasive capacity of SiHa and HeLa cells, and these effects were fully compromised by reintroduction of LDHA. In conclusion, our findings demonstrated that deregulated miR-34a/LDHA axis induced by HPV E6/p53 signaling facilitates tumor growth and invasion through regulating Warburg effect in cervical cancer, and provided new insights into the mechanism by which miR-34a contributes to the development and progression of cervical cancer.

  17. The analytical biochemistry of chromium.

    OpenAIRE

    Katz, S A

    1991-01-01

    The essentiality and carcinogenicity of chromium depend on its chemical form. Oxidation state and solubility are particularly important in determining the biological effects of chromium compounds. For this reason, total chromium measurements are of little value in assessing its nutritional benefits or its toxicological hazards. Aqueous sodium carbonate-sodium hydroxide solutions have been successfully used for extracting hexavalent chromium from a variety of environmental and biological matri...

  18. Chromium in potatoes

    International Nuclear Information System (INIS)

    Chromium concentration in potatoes was determined, and tubes were labeled either intrinsically or extrinsically with radioactive chromate (51Cr). A labeled chromium complex was isolated from preparations of raw, baked, or fried potatoes and chromatographed on gel permeation media. Potato pulp and peel contained 1.63 and 2.70 μg of Cr/g tissue, respectively. There was no correlation between the two, nor did they respond similarly to changes of variety or locations. No significant differences were apparent in relative migration of the isolated complexes except between raw and cooked extrinsically labeled preparations

  19. Dynamics of p53 and NF-κB regulation in response to DNA damage and identification of target proteins suitable for therapeutic intervention

    Directory of Open Access Journals (Sweden)

    Poltz Rainer

    2012-09-01

    Full Text Available Abstract Background The genome is continuously attacked by a variety of agents that cause DNA damage. Recognition of DNA lesions activates the cellular DNA damage response (DDR, which comprises a network of signal transduction pathways to maintain genome integrity. In response to severe DNA damage, cells undergo apoptosis to avoid transformation into tumour cells, or alternatively, the cells enter permanent cell cycle arrest, called senescence. Most tumour cells have defects in pathways leading to DNA repair or apoptosis. In addition, apoptosis could be counteracted by nuclear factor kappa B (NF-κB, the main anti-apoptotic transcription factor in the DDR. Despite the high clinical relevance, the interplay of the DDR pathways is poorly understood. For therapeutic purposes DNA damage signalling processes are induced to induce apoptosis in tumour cells. However, the efficiency of radio- and chemotherapy is strongly hampered by cell survival pathways in tumour cells. In this study logical modelling was performed to facilitate understanding of the complexity of the signal transduction networks in the DDR and to provide cancer treatment options. Results Our comprehensive discrete logical model provided new insights into the dynamics of the DDR in human epithelial tumours. We identified new mechanisms by which the cell regulates the dynamics of the activation of the tumour suppressor p53 and NF-κB. Simulating therapeutic intervention by agents causing DNA single-strand breaks (SSBs or DNA double-strand breaks (DSBs we identified candidate target proteins for sensitization of carcinomas to therapeutic intervention. Further, we enlightened the DDR in different genetic diseases, and by failure mode analysis we defined molecular defects putatively contributing to carcinogenesis. Conclusion By logic modelling we identified candidate target proteins that could be suitable for radio- and chemotherapy, and contributes to the design of more effective

  20. The p53 pathway in breast cancer

    OpenAIRE

    Gasco, Milena; Shami, Shukri; Crook, Tim

    2002-01-01

    p53 mutation remains the most common genetic change identified in human neoplasia. In breast cancer, p53 mutation is associated with more aggressive disease and worse overall survival. The frequency of mutation in p53 is, however, lower in breast cancer than in other solid tumours. Changes, both genetic and epigenetic, have been identified in regulators of p53 activity and in some downstream transcriptional targets of p53 in breast cancers that express wild-type p53. Molecular pathological an...

  1. Radiochemical Study on the Separation of Chromium-51 from the Irradiated Target by Using Commercial and/or Synthesized Ion Exchanger

    International Nuclear Information System (INIS)

    This work involves the following steps:1- Preparation of Triton X-100 Cerium(IV) Phosphate (TX-100CeP) as a surface active ion exchanger or organometallic molecules. 2- Characterization of the TX-100CeP by different methods (i.e. IR, TGA/DTA X-ray diffraction, X-ray fluorescence and elemental analysis). 3- Development a method for separation and quantification of Cr(III) and Cr(VI) by using high pressure liquid chromatography (HPLC). 4- Separation of 51Cr(III) from Cr(VI) in the target of K2CrO4 on TX-100CeP and Permutit as a commercial ion exchanger. 5- Quality control on the separated 51Cr(III).

  2. Expression of p53 Target Genes in the Early Phase of Long-Term Potentiation in the Rat Hippocampal CA1 Area

    Science.gov (United States)

    Pustylnyak, Vladimir O.; Lisachev, Pavel D.; Shtark, Mark B.

    2015-01-01

    Gene expression plays an important role in the mechanisms of long-term potentiation (LTP), which is a widely accepted experimental model of synaptic plasticity. We have studied the expression of at least 50 genes that are transcriptionally regulated by p53, as well as other genes that are related to p53-dependent processes, in the early phase of LTP. Within 30 min after Schaffer collaterals (SC) tetanization, increases in the mRNA and protein levels of Bax, which are upregulated by p53, and a decrease in the mRNA and protein levels of Bcl2, which are downregulated by p53, were observed. The inhibition of Mdm2 by nutlin-3 increased the basal p53 protein level and rescued its tetanization-induced depletion, which suggested the involvement of Mdm2 in the control over p53 during LTP. Furthermore, nutlin-3 caused an increase in the basal expression of Bax and a decrease in the basal expression of Bcl2, whereas tetanization-induced changes in their expression were occluded. These results support the hypothesis that p53 may be involved in transcriptional regulation during the early phase of LTP. We hope that the presented data may aid in the understanding of the contribution of p53 and related genes in the processes that are associated with synaptic plasticity. PMID:25767724

  3. Expression of p53 Target Genes in the Early Phase of Long-Term Potentiation in the Rat Hippocampal CA1 Area

    Directory of Open Access Journals (Sweden)

    Vladimir O. Pustylnyak

    2015-01-01

    Full Text Available Gene expression plays an important role in the mechanisms of long-term potentiation (LTP, which is a widely accepted experimental model of synaptic plasticity. We have studied the expression of at least 50 genes that are transcriptionally regulated by p53, as well as other genes that are related to p53-dependent processes, in the early phase of LTP. Within 30 min after Schaffer collaterals (SC tetanization, increases in the mRNA and protein levels of Bax, which are upregulated by p53, and a decrease in the mRNA and protein levels of Bcl2, which are downregulated by p53, were observed. The inhibition of Mdm2 by nutlin-3 increased the basal p53 protein level and rescued its tetanization-induced depletion, which suggested the involvement of Mdm2 in the control over p53 during LTP. Furthermore, nutlin-3 caused an increase in the basal expression of Bax and a decrease in the basal expression of Bcl2, whereas tetanization-induced changes in their expression were occluded. These results support the hypothesis that p53 may be involved in transcriptional regulation during the early phase of LTP. We hope that the presented data may aid in the understanding of the contribution of p53 and related genes in the processes that are associated with synaptic plasticity.

  4. The fate of chromium during tropical weathering

    DEFF Research Database (Denmark)

    Berger, Alfons; Frei, Robert

    2014-01-01

    We performed a mineral, geochemical and Cr–Sr–Pb isotope study on a laterite profile developed on ca. 540 Ma old tonalitic bedrock in Madagascar with special emphasis on the behavior of chromium during tropical weathering. The observed strong depletions of Ca, Si, and P, and enrichment of Fe and Al...... of the soil profile relative to stage one altered saprolite. This gain in Cr is accompanied by decreasing δ53Cr values and can be explained by partial immobilization (possibly by adsorption/coprecipitation on/with Fe-oxy-hydroxides) of mobile Cr(III) during upward transport in the weathering profile....... The negatively fractionated δ53Cr values measured in the weathering profile relative to the unaltered tonalitic bedrock characterized by a high temperature magmatic inventory Cr isotope signature are consistent with loss of a positively fractionated Cr(VI) pool formed during weathering. The predicted existence...

  5. Chromium, chromium isotopes and selected trace elements, western Mojave Desert, USA

    Energy Technology Data Exchange (ETDEWEB)

    Izbicki, John A. [U.S. Geological Survey, 4165 Spruance Road, Suite O, San Diego, CA 92123 (United States)], E-mail: jaizbick@usgs.gov; Ball, James W. [U.S. Geological Survey, 3215 Marine Street, Boulder, Colorado, CO 80303 (United States); Bullen, Thomas D. [U.S. Geological Survey, 345 Middlefield Road, Building 15, McKelvey Building, MS-420, Menlo Park, CA 94025 (United States); Sutley, Stephen J. [Denver Federal Center, P.O. Box 25046, MS-964, Denver, CO 80225-0046 (United States)

    2008-05-15

    Chromium(VI) concentrations in excess of the California Maximum Contaminant Level (MCL) of 50 {mu}g/L occur naturally in alkaline, oxic ground-water in alluvial aquifers in the western Mojave Desert, southern California. The highest concentrations were measured in aquifers eroded from mafic rock, but Cr(VI) as high as 27 {mu}g/L was measured in aquifers eroded from granitic rock. Chromium(VI) concentrations did not exceed 5 {mu}g/L at pH < 7.5 regardless of geology. {delta}{sup 53}Cr values in native ground-water ranged from 0.7 to 5.1 per mille and values were fractionated relative to the average {delta}{sup 53}Cr composition of 0 per mille in the earth's crust. Positive {delta}{sup 53}Cr values of 1.2 and 2.3 per mille were measured in ground-water recharge areas having low Cr concentrations, consistent with the addition of Cr(VI) that was fractionated on mineral surfaces prior to entering solution. {delta}{sup 53}Cr values, although variable, did not consistently increase or decrease with increasing Cr concentrations as ground-water flowed down gradient through more oxic portions of the aquifer. However, increasing {delta}{sup 53}Cr values were observed as dissolved O{sub 2} concentrations decreased, and Cr(VI) was reduced to Cr(III), and subsequently removed from solution. As a result, the highest {delta}{sup 53}Cr values were measured in water from deep wells, and wells in discharge areas near dry lakes at the downgradient end of long flow paths through alluvial aquifers. {delta}{sup 53}Cr values at an industrial site overlying mafic alluvium having high natural background Cr(VI) concentrations ranged from -0.1 to 3.2 per mille . Near zero {delta}{sup 53}Cr values at the site were the result of anthropogenic Cr. However, mixing with native ground-water and fractionation of Cr within the plume increased {delta}{sup 53}Cr values at the site. Although {delta}{sup 53}Cr was not necessarily diagnostic of anthropogenic Cr, it was possible to identify the extent

  6. Deficiency in p53 is required for doxorubicin induced transcriptional activation of NF-κB target genes in human breast cancer

    Science.gov (United States)

    Dalmases, Alba; González, Irene; Menendez, Silvia; Arpí, Oriol; Corominas, Josep Maria; Servitja, Sonia; Tusquets, Ignasi; Chamizo, Cristina; Rincón, Raúl; Espinosa, Lluis; Bigas, Anna; Eroles, Pilar; Furriol, Jessica; Lluch, Anna; Rovira, Ana; Albanell, Joan; Rojo, Federico

    2014-01-01

    NF-κB has been linked to doxorubicin resistance in breast cancer patients. NF-κB nuclear translocation and DNA binding in doxorubicin treated-breast cancer cells have been extensively examined; however its functional relevance at transcriptional level on NF-κB -dependent genes and the biological consequences are unclear. We studied NF-κB -dependent gene expression induced by doxorubicin in breast cancer cells and fresh human cancer specimens with different genetic backgrounds focusing on their p53 status. NF-κB -dependent signature of doxorubicin was identified by gene expression microarrays in breast cancer cells treated with doxorubicin and the IKKβ-inhibitor MLN120B, and confirmed ex vivo in human cancer samples. The association with p53 was functionally validated. Finally, NF-κB activation and p53 status was determined in a cohort of breast cancer patients treated with adjuvant doxorubicin-based chemotherapy. Doxorubicin treatment in the p53-mutated MDA-MB-231 cells resulted in NF NF-κB driven-gene transcription signature. Modulation of genes related with invasion, metastasis and chemoresistance (ICAM-1, CXCL1, TNFAIP3, IL8) were confirmed in additional doxorubicin-treated cell lines and fresh primary human breast tumors. In both systems, p53-defcient background correlated with the activation of the NF-κB -dependent signature. Furthermore, restoration of p53WT in the mutant p53 MDA-MB-231 cells impaired NF-κB driven transcription induced by doxorubicin. Moreover, a p53 deficient background and nuclear NF-κB /p65 in breast cancer patients correlated with reduced disease free-survival. This study supports that p53 deficiency is necessary for a doxorubicin driven NF-κB -response that limits doxorubicin cytotoxicity in breast cancer and is linked to an aggressive clinical behavior. PMID:24344116

  7. Ferrous sulphate mono and heptahydrate reduction of hexavalent chromium in cement: effectiveness and storability

    OpenAIRE

    Valverde, J. L.; Lobato, J.; I. Fernández; Marijuán, L.; Pérez-Mohedano, S.; Talero, R.

    2005-01-01

    In Community legislation, substances containing hexavalent chromium are classified as carcinogenic, mutagenic and sensitizing. In cement, hexavalent chromium intensifies sensitization and may set off severe allergic reactions in workers in routine contact with the product, whether in the factory or on construction sites. The allergic or contact dermatitis causes is a very painful disease that may lead to permanent worker disability. According to Directive 2003/53/EC of the European Parliament...

  8. p53 down-regulates SARS coronavirus replication and is targeted by the SARS-unique domain and PLpro via E3 ubiquitin ligase RCHY1.

    Science.gov (United States)

    Ma-Lauer, Yue; Carbajo-Lozoya, Javier; Hein, Marco Y; Müller, Marcel A; Deng, Wen; Lei, Jian; Meyer, Benjamin; Kusov, Yuri; von Brunn, Brigitte; Bairad, Dev Raj; Hünten, Sabine; Drosten, Christian; Hermeking, Heiko; Leonhardt, Heinrich; Mann, Matthias; Hilgenfeld, Rolf; von Brunn, Albrecht

    2016-08-30

    Highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) has developed strategies to inhibit host immune recognition. We identify cellular E3 ubiquitin ligase ring-finger and CHY zinc-finger domain-containing 1 (RCHY1) as an interacting partner of the viral SARS-unique domain (SUD) and papain-like protease (PL(pro)), and, as a consequence, the involvement of cellular p53 as antagonist of coronaviral replication. Residues 95-144 of RCHY1 and 389-652 of SUD (SUD-NM) subdomains are crucial for interaction. Association with SUD increases the stability of RCHY1 and augments RCHY1-mediated ubiquitination as well as degradation of p53. The calcium/calmodulin-dependent protein kinase II delta (CAMK2D), which normally influences RCHY1 stability by phosphorylation, also binds to SUD. In vivo phosphorylation shows that SUD does not regulate phosphorylation of RCHY1 via CAMK2D. Similarly to SUD, the PL(pro)s from SARS-CoV, MERS-CoV, and HCoV-NL63 physically interact with and stabilize RCHY1, and thus trigger degradation of endogenous p53. The SARS-CoV papain-like protease is encoded next to SUD within nonstructural protein 3. A SUD-PL(pro) fusion interacts with RCHY1 more intensively and causes stronger p53 degradation than SARS-CoV PL(pro) alone. We show that p53 inhibits replication of infectious SARS-CoV as well as of replicons and human coronavirus NL63. Hence, human coronaviruses antagonize the viral inhibitor p53 via stabilizing RCHY1 and promoting RCHY1-mediated p53 degradation. SUD functions as an enhancer to strengthen interaction between RCHY1 and nonstructural protein 3, leading to a further increase in in p53 degradation. The significance of these findings is that down-regulation of p53 as a major player in antiviral innate immunity provides a long-sought explanation for delayed activities of respective genes. PMID:27519799

  9. Global genomic profiling reveals an extensive p53-regulated autophagy program contributing to key p53 responses

    OpenAIRE

    Kenzelmann Broz, Daniela; Spano Mello, Stephano; Bieging, Kathryn T.; Jiang, Dadi; Rachel L Dusek; Brady, Colleen A.; Sidow, Arend; Attardi, Laura D.

    2013-01-01

    To gain new insights into p53 biology, Kenzelmann Broz et al. used high-throughput sequencing to analyze global p53 transcriptional networks in primary mouse embryo fibroblasts in response to DNA damage. This approach identified autophagy genes as direct p53 target genes. p53-induced autophagy was important for both p53-dependent apoptosis and transformation suppression by p53. These data highlight an intimate connection between p53 and autophagy and suggest that autophagy contributes to p53-...

  10. Groundwater contaminant by hexavalent chromium

    Energy Technology Data Exchange (ETDEWEB)

    Parsons, C. [Univ. of Texas, Austin, TX (United States)

    1995-11-01

    Oxidation of trivalent chromium to hexavalent chromium has been investigated as a function of total manganese in soils as well as various incubation conditions. Chromium and manganese contents were analyzed by atomic absorption (graphite furnace and flame emission respectively) following acid digestion. Total hexavalent chromium generation capacity was determined by addition of 0.001 M CrCL3, incubation, and analysis by s-diphenyl carbazide. Samples were then leached with CaSO{sub 4} and MgSO{sub 4} and incubated in various environments (oven, freeze-drier, field moist, ultrafreeze) to test for geogenic generation of Cr(IV). The degree of geogenic generation of hexavalent chromium was compared with total Mn and Cr content as well as hexavalent generational capacity.

  11. Chromium trace determination in inorganic, organic and aqueous samples with isotope dilution mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Goetz, A.; Heumann, K.G.

    1988-06-01

    It is shown that chromium traces in different inorganic, organic and aqueous samples can be determined over a wide concentration range with isotope dilution mass spectrometry. Electrolytic or chromatographic isolation steps are added to a system of sample preparation units for oligo-element determinations to analyse chromium besides other heavy metals. The isotope ratio /sup 52/Cr//sup 53/Cr is measured in a thermal quadrupole mass spectrometer using a single-filament ion source with additions of silica gel and boric acid. In water samples, which contain humic substances, chromium concentrations of a few ng/g and less can be determined with relative standard deviations of about 1% and better. A differentiation is possible into the total chromium content and into chromium species which carry out isotope exchange reactions and those which are inert for an isotope exchange reaction. The chromium concentrations of four standard reference materials (two plants BCR 60 and 61, one tissue BCR 278, one sewage sludge BCR 144), which are not certified for chromium, are determined to be 29.4 ..mu..g/g, 534 ..mu..g/g, 0.78 ..mu..g/g, and 466.1 ..mu..g/g, respectively. In three different sediments total chromium concentrations between 100 ..mu..g/g and 180 ..mu..g/g are analysed with relative standard deviations of 0.6%-1.2%.

  12. Evaluating Foraminifera as an Archive for Seawater Chromium Isotopic Composition

    Science.gov (United States)

    Wang, X.; Planavsky, N.; Hull, P. M.; Tripati, A.; Reinhard, C.; Zou, H.; Elder, L. E.; Henehan, M. J.

    2015-12-01

    In recent years there has been growing interest in using chromium isotopes (δ53Cr) as a proxy to investigate the redox evolution of Earth's ocean-atmosphere system throughout geological history. Potential archives for seawater δ53Cr that have been identified to date include iron formations and organic-rich siliciclastic sediments. However, these types of sediments are not common and they are discontinuous over geologic time. As a result, alternative types of archives are needed. Here we evaluate the utility of foraminifera tests as a recorder of seawater δ53Cr. Core-tops used were from different ocean basins. Mono-specific samples of Globigerinoides sacculifer, Orbulina universa, Pulleniatina obliquiloculata, Globoratalia crassula-crassaformis, Globoratalia truncatulinoides, and Globigerinella siphonifera were isolated to investigate inter-species isotope fractionation. Chromium concentrations were measured by isotope dilution method to be 0.1-0.3 μg/g. The δ53Cr values of these species range from 0.2‰ to 2.4‰, with an analytical uncertainty of 0.3‰ (95% confidence). Despite the high analytical uncertainty due to the extremely low levels of Cr present, there is still large detectable variation in foraminiferal δ53Cr values, which overlap presently available seawater values (Bonnand et al., 2013; Scheiderich et al., 2015). Possible explanations for such variations in foraminiferal δ53Cr values include heterogeneity of seawater δ53Cr in the modern oceans, and/or photobiochemical redox cycling of Cr in the surface oceans. Therefore, care should be taken when using foraminifera to reconstruct past seawater δ53Cr values. ReferencesBonnand, P., James, R., Parkinson, I., Connelly, D., Fairchild, I., 2013. The chromium isotopic composition of seawater and marine carbonates. Earth and Planetary Science Letters, 382: 10-20. Scheiderich, K., Amini, M., Holmden, C., Francois, R., 2015. Global variability of chromium isotopes in seawater demonstrated by Pacific

  13. On texture formation of chromium electrodeposits

    DEFF Research Database (Denmark)

    Nielsen, Christian Bergenstof; Leisner, Peter; Horsewell, Andy

    1998-01-01

    The microstructure, texture and hardness of electrodeposited hard, direct current (DC) chromium and pulsed reversed chromium has been investigated. These investigations suggest that the growth and texture of hard chromium is controlled by inhibition processes and reactions. Further, it has been e...... established that codeposition of Cr2O3 nanoparticles is a general feature of DC chromium electrodeposition....

  14. The p53 target gene desmocollin 3 acts as a novel tumor suppressor through inhibiting EGFR/ERK pathway in human lung cancer.

    Science.gov (United States)

    Cui, Tiantian; Chen, Yuan; Yang, Linlin; Knösel, Thomas; Huber, Otmar; Pacyna-Gengelbach, Manuela; Petersen, Iver

    2012-12-01

    Desmosomes are intercellular junctions that confer strong cell-cell adhesion. Altered expression of desmocollin 3 (DSC3), a member of the desmosomal cadherin family, was found in various cancers; however, its functional involvement in carcinogenesis has not yet been elucidated. Expression/localization of DSC3 was analyzed by real-time reverse transcription-PCR, western blotting, immunofluorescence and immunohistochemistry. Methylation status of DSC3 was examined by demethylation tests, methylation-specific PCR and bisulfite sequencing. It turned out that downregulation of DSC3 in lung cancer cells was associated with DNA hypermethylation. In primary lung tumors, DSC3 was a potential diagnostic marker for lung squamous cell carcinoma, and DSC3 DNA hypermethylation was correlated with poor clinical outcome. To investigate the effect of the tumor suppressor gene p53 on DSC3, transient transfection with a wild-type p53-expression vector was performed. Overexpression of p53 resulted in an increased expression of DSC3 in a DSC3-unmethylated lung cancer cell line H2170, but not in H1299, a DSC3-methylated cell line. However, combination of p53 transfection with demethylation agent 5-aza-2'-deoxycytidine treatment led to increased expression of DSC3 in H1299 cells. Furthermore, functional studies after stable transfection of a DSC3 expression vector showed that ectopic expression of DSC3 inhibited cell proliferation, anchorage-independent growth, migration, as well as invasion, and most interestingly led to reduced phosphorylation levels of extracellular signal-regulated kinase1/2. Taken together, our data suggested that DSC3 acts as a novel tumor suppressor gene through inhibition of epidermal growth factor receptor/extracellular signal-regulated kinase signaling in lung cancer cells. PMID:22941060

  15. The tumor suppressor p53 regulates its own transcription.

    OpenAIRE

    Deffie, A; H. Wu; Reinke, V.; Lozano, G.

    1993-01-01

    The ability of p53 to suppress transformation correlates with its ability to activate transcription. To identify targets of p53 transactivation, we examined the p53 promoter itself. Northern (RNA) analysis and transient transfection experiments showed that p53 transcriptionally regulated itself. A functionally inactive mutant p53 could not regulate the p53 promoter. Deletion analysis of the p53 promoter delineated sequences between +22 and +67 as being critical for regulation. Electrophoretic...

  16. Chromium isotope variations

    DEFF Research Database (Denmark)

    D'Arcy, Joan Mary

    fractionate during oxidative weathering of the continents. High river water δ53Cr values (+1.6‰) indicate that dissolved Cr has been back-reduced either in the weathering profile or during river transport. The main conclusion from this study is that δ53Cr value for continental runoff is not uniform....... The positive excursion does not correlated with other redox proxies (carbon and sulphur stable isotopes profiles from the Lower Ordovician), suggesting that Cr isotopes behave non-conservatively and are more sensitive to changes in local redox conditions. These results demonstrate that Cr isotope composition...

  17. The fluorescent two-hybrid assay to screen for protein-protein interaction inhibitors in live cells: targeting the interaction of p53 with Mdm2 and Mdm4.

    Science.gov (United States)

    Yurlova, Larisa; Derks, Maarten; Buchfellner, Andrea; Hickson, Ian; Janssen, Marc; Morrison, Denise; Stansfield, Ian; Brown, Christopher J; Ghadessy, Farid J; Lane, David P; Rothbauer, Ulrich; Zolghadr, Kourosh; Krausz, Eberhard

    2014-04-01

    Protein-protein interactions (PPIs) are attractive but challenging targets for drug discovery. To overcome numerous limitations of the currently available cell-based PPI assays, we have recently established a fully reversible microscopy-assisted fluorescent two-hybrid (F2H) assay. The F2H assay offers a fast and straightforward readout: an interaction-dependent co-localization of two distinguishable fluorescent signals at a defined spot in the nucleus of mammalian cells. We developed two reversible F2H assays for the interactions between the tumor suppressor p53 and its negative regulators, Mdm2 and Mdm4. We then performed a pilot F2H screen with a subset of compounds, including small molecules (such as Nutlin-3) and stapled peptides. We identified five cell-penetrating compounds as potent p53-Mdm2 inhibitors. However, none exhibited intracellular activity on p53-Mdm4. Live cell data generated by the F2H assays enable the characterization of stapled peptides based on their ability to penetrate cells and disrupt p53-Mdm2 interaction as well as p53-Mdm4 interaction. Here, we show that the F2H assays enable side-by-side analysis of substances' dual Mdm2-Mdm4 activity. In addition, they are suitable for testing various types of compounds (e.g., small molecules and peptidic inhibitors) and concurrently provide initial data on cellular toxicity. Furthermore, F2H assays readily allow real-time visualization of PPI dynamics in living cells. PMID:24476585

  18. Chromium reduction in Pseudomonas putida.

    OpenAIRE

    Ishibashi, Y.; Cervantes, C; Silver, S

    1990-01-01

    Reduction of hexavalent chromium (chromate) to less-toxic trivalent chromium was studied by using cell suspensions and cell-free supernatant fluids from Pseudomonas putida PRS2000. Chromate reductase activity was associated with soluble protein and not with the membrane fraction. The crude enzyme activity was heat labile and showed a Km of 40 microM CrO4(2-). Neither sulfate nor nitrate affected chromate reduction either in vitro or with intact cells.

  19. Small-molecule modulators of p53 family signaling and antitumor effects in p53-deficient human colon tumor xenografts

    OpenAIRE

    Wang, Wenge; Kim, Seok-Hyun; El-Deiry, Wafik S

    2006-01-01

    p53 deficiency is common in almost all human tumors and contributes to an aggressive chemo- or radiotherapy-resistant phenotype, therefore providing a target for drug development. Molecular targeting to restore wild-type p53 activity has been attempted in drug development and has led to the identification of CP-31398, PRIMA1, and the Nutlins. However, strategies targeting p53-activated transcriptional responses or p53 family member expression in p53-deficient tumors have yet to be explored. H...

  20. p53 isoforms change p53 paradigm

    OpenAIRE

    Bourdon, JC

    2014-01-01

    Although p53 defines cellular responses to cancer treatment it is not clear how p53 can be used to control cell fate outcome. Data demonstrate that so-called p53 does not exist as a single protein, but is in fact a group of p53 protein isoforms whose expression can be manipulated to control the cellular response to treatment.

  1. Arginine methylation regulates the p53 response

    DEFF Research Database (Denmark)

    Jansson, Martin; Durant, Stephen T; Cho, Er-Chieh;

    2008-01-01

    on the p53 response. We show that the protein arginine methyltransferase (PRMT) 5, as a co-factor in a DNA damage responsive co-activator complex that interacts with p53, is responsible for methylating p53. Arginine methylation is regulated during the p53 response and affects the target gene specificity......Activation of the p53 tumour suppressor protein in response to DNA damage leads to apoptosis or cell-cycle arrest. Enzymatic modifications are widely believed to affect and regulate p53 activity. We describe here a level of post-translational control that has an important functional consequence...

  2. p53 Acetylation: Regulation and Consequences

    OpenAIRE

    Reed, Sara M.; Quelle, Dawn E.

    2014-01-01

    Post-translational modifications of p53 are critical in modulating its tumor suppressive functions. Ubiquitylation, for example, plays a major role in dictating p53 stability, subcellular localization and transcriptional vs. non-transcriptional activities. Less is known about p53 acetylation. It has been shown to govern p53 transcriptional activity, selection of growth inhibitory vs. apoptotic gene targets, and biological outcomes in response to diverse cellular insults. Yet recent in vivo ev...

  3. Ecotoxicological tests with cadmium and chromium using postlarvae of silverside Odontesthes (Austromenidia regia regia Hildebrand

    Directory of Open Access Journals (Sweden)

    Giovana Vera

    2014-06-01

    Full Text Available In the present paper, the mean effective concentrations (EC50% of cadmium (Cd+2 and chromium (Cr+6 using postlarvae of the silverside fish Odontesthes (Austromenidia regia regia were determined. The postlarvae were exposed to different concentrations of the metals, between 0,142 and 1,208 mg.L–1 of cadmium and between 0,53 and 33,74 mg.L–1 of chromium. The mean effective concentrations (EC50% obtained were 0,648 mg.L–1 of cadmium (at 96 h and 2,68 mg.L–1 of chromium (at 96 h. Comparatively, cadmium is more toxic than chromium, and silverside is more tolerant than other organisms.

  4. Galvanic cells including cobalt-chromium alloys.

    Science.gov (United States)

    Gjerdet, N R

    1980-01-01

    Galvanic cells may be created when dentures made of cobalt-chromium alloys are placed on teeth with metallic restorations. The power of such cells was evaluated in an in vitro galvanic using amalgams, gold alloy, and nickel-chromium alloys. The amalgams and one of the nickel-chromium alloys revealed high corrosion currents when placed in contact with cobalt-chromium alloy, the conventional amalgam showing the highest values. The gold alloy and another nickel-chromium alloy exhibited low corrosion currents and they were noble with respect to cobalt-chromium.

  5. Hydrogen permeation through chromium

    International Nuclear Information System (INIS)

    Steady state and non-steady state measurements of hydrogen permeation through metallic chromium are reported. The experiments have been conducted by use of hydrogen and deuterium within a pressure range of 10-8 - 1 bar and temperatures between 600 - 8000C. Numerical values for the physical quantities permeability, diffusion constant and solubility could be derived. At an upstream pressure above around 10-3 bar classical Sieverts-low was found (permeation rate proportional √p) with activation energies Qsub(perm) = 65 kJoule/mole, Qsub(Diff) = 4-8 kJoule/mole, Qsub(Sol) = 57-61 kJoule/mole for the respective processes involved. The isotopic effect between H and D of the permeabilities could be represented by a factor of 1,5 independence on temperature. All non steady-state measurements could be approximated reasonably well by classical diffusion kinetics. Below up-stream pressures of approx.= 10-7 bar the kinetics was no longer diffusion controlled, the dependence on up-stream pressure changed from √p -> p, the activation energy for permetation increased to 127 kJoule/mole and the isotopic factor resulted in about 2-3. (orig.)

  6. MicroRNA-96 promotes the proliferation of colorectal cancer cells and targets tumor protein p53 inducible nuclear protein 1, forkhead box protein O1 (FOXO1) and FOXO3a.

    Science.gov (United States)

    Gao, Feng; Wang, Wenhui

    2015-02-01

    MicroRNAs (miRNAs) are a conserved class of small, endogenous, non protein-coding RNA molecules that are capable of regulating gene expression at post-transcriptional levels and are involved in diverse cellular processes, including cancer pathogenesis. It has previously been reported that miRNA-96 (miR-96) is overexpressed in human colorectal cancer (CRC). However, the underlying mechanism of miR-96 regulation in CRC remains to be elucidated. In the present study, miR-96 was confirmed to be upregulated in CRC tissues by reverse transcription quantitative polymerase chain reaction. MTT assay, colony formation assay and cell cycle analysis revealed that miR-96 overexpression led to increased tumor cell viability, colony formation ability and cell cycle progression. By contrast, inhibition of miR-96 resulted in the suppression of cell proliferation. It was also demonstrated that miR-96 reduced the messenger RNA and protein expression levels of tumor protein p53 inducible nuclear protein 1 (TP53INP1), forkhead box protein O1 (FOXO1) and FOXO3a, which are closely associated with cell proliferation. A luciferase reporter assay indicated that miR-96 inhibited luciferase intensity controlled by the 3'UTRs of TP53INP1, FOXO1 and FOXO3a. In conclusion, the results of the present study demonstrated that miR-96 contributed to CRC cell growth and that TP53INP1, FOXO1 and FOXO3a were direct targets of miR-96, suggesting that miR-96 may have the potential to be used in the development of miRNA‑based therapies for CRC patients.

  7. Characterisation of exposure to total and hexavalent chromium of welders using biological monitoring.

    NARCIS (Netherlands)

    Scheepers, P.T.J.; Heussen, G.A.; Peer, P.G.M.; Verbist, K.; Anzion, R.; Willems, J.

    2008-01-01

    Inhalation exposure to total and hexavalent chromium (TCr and HCr) was assessed by personal air sampling and biological monitoring in 53 welders and 20 references. Median inhalation exposure levels of TCr were 1.3, 6.0, and 5.4 microg/m(3) for welders of mild steel (MS, <5% alloys), high alloy st

  8. p53 regulates the transcription of its Delta133p53 isoform through specific response elements contained within the TP53 P2 internal promoter.

    Science.gov (United States)

    Marcel, V; Vijayakumar, V; Fernández-Cuesta, L; Hafsi, H; Sagne, C; Hautefeuille, A; Olivier, M; Hainaut, P

    2010-05-01

    The tumor suppressor p53 protein is activated by genotoxic stress and regulates genes involved in senescence, apoptosis and cell-cycle arrest. Nine p53 isoforms have been described that may modulate suppressive functions of the canonical p53 protein. Among them, Delta133p53 lacks the 132 proximal residues and has been shown to modulate p53-induced apoptosis and cell-cycle arrest. Delta133p53 is expressed from a specific mRNA, p53I4, driven by an alternative promoter P2 located between intron 1 and exon 5 of TP53 gene. Here, we report that the P2 promoter is regulated in a p53-dependent manner. Delta133p53 expression is increased in response to DNA damage by doxorubicin in p53 wild-type cell lines, but not in p53-mutated cells. Chromatin immunoprecipitation and luciferase assays using P2 promoter deletion constructs indicate that p53 binds functional response elements located within the P2 promoter. We also show that Delta133p53 does not bind specifically to p53 consensus DNA sequence in vitro, but competes with wild-type p53 in specific DNA-binding assays. Finally, we report that Delta133p53 counteracts p53-dependent growth suppression in clonogenic assays. These observations indicate that Delta133p53 is a novel target of p53 that may participate in a negative feedback loop controlling p53 function. PMID:20190805

  9. Loss of the p53/p63 Target PERP is an Early Event in Oral Carcinogenesis and Correlates with Higher Rate of Local Relapse

    Science.gov (United States)

    Kong, Christina S.; Cao, Hongbin; Kwok, Shirley; Nguyen, Catherine M.; Jordan, Richard C.; Beaudry, Veronica G.; Attardi, Laura D.; Le, Quynh-Thu

    2012-01-01

    BACKGROUND PERP is a p53/p63 regulated gene encoding a desmosomal protein that plays a critical role in cell-cell adhesion and tumor suppression. STUDY DESIGN We evaluated PERP expression in different grades of oral dysplasia (34 cases) and at different stages of invasive squamous cell carcinoma (SCC), and correlated the latter with clinical outcome. A tissue microarray (TMA) consisting of non-dysplastic mucosa, carcinoma in situ, SCC and nodal metastases from 33 patients with HPV-negative SCC was stained for PERP and E-cadherin. RESULTS Complete loss of PERP expression was associated with worse local control in patients with SCC. The 5-year local control rate was 91% for patients with partial PERP loss versus 31% for those with complete loss (p = 0.01). CONCLUSIONS This is the first study to show that loss of PERP expression correlates with the transition to SCC and with increased local relapse in patients with oral cavity SCC. PMID:23217540

  10. Laser propagation in a gas-filled target with 0.53 and 0.35 μm at various electron densities on Nova

    International Nuclear Information System (INIS)

    Thin-walled gas-filled targets have been irradiated with the Nova laser in order to measure laser propagation into a gas to form a plasma with electron density ranging from 0.05--0.25 nc. The targets consist of a thin (0.6--1.0 μm) polyimide skin that is stretched across the two faces of a washer, and then inflated to hold 1 atmosphere of gas. The experiments were done with ≤ 1 atmosphere of neopentane (3 mg/cm3). Additional shots were done to propagate a Nova beam into a preformed plasma by using two opposing beams with a relative delay. Peak laser irradiance on the target was varied from 3 x 1014 to 6 x 1015 W/cm2. The beam propagation into the gas was measured from streaked and gated x-ray images taken normal to the direction of laser propagation. Plasma temperature was measured spectroscopically with dopants in the gas-fill mixture. The effect of phase plates and SSD on beam propagation into the gas were studied using an f/4 and an f/8 laser beam on Nova. Lateral heat flow was also measured from the gated x-ray imaging. The propagation of the laser burn-front is compared to LASNEX calculations. A mm-scale plasma is created at approximately 1--1.5 keV with 2--3 kJ of laser energy delivered to the target in a 1 ns square-profile pulse

  11. Chromium Isotopes in Marine Carbonates - an Indicator for Climatic Change?

    Science.gov (United States)

    Frei, R.; Gaucher, C.

    2010-12-01

    Chromium (Cr) stable isotopes experience an increased interest as a tracer of Cr (VI) reduction in groundwater and thus showed their potential as a monitor of remediation of anthropogenic and natural contamination in water (Berna et al., 2009; Izbicki et al., 2008). Chromium stable isotopes in Fe-rich chemical sediments (BIFs and Fe-cherts) have recently also been used as a tracer for Earth's atmospheric oxygenation through time (Frei et al., 2009). We have applied the Cr isotope system to organic-rich carbonates from a late Ediacaran succession in Uruguay (Polanco Formation), from which we have previously analyzed BIFs with extremely fractionated (δ53Cr up to 5.0 ‰) Cr isotope signatures that are part of an underlying deep water clastic sediment (shale-dominated) sequence (Yerbal Formation) deposited in a glacio-marine environment (Gaucher et al.,2004). δ53Cr values of organic rich carbonates correlate with positive and negative carbon isotope excursions (δ13C PDB between -3 and +3 ‰) and with systematic changes in strontium isotope compositions, commonly interpreted as to reflect fluctuations in organic (photosynthetic algae) production related to fluctuations in atmospheric oxygen and weathering intensities, respectively. Slightly positively fractioned δ53Cr values (up to +0.25‰), paralleling positive (δ13C PDB and 87Sr/86Sr ratio excursions would thereby trace elevated atmospheric oxygen levels/pulses possibly related to glacier retreat/melting stages that caused bioproductivity to increase. While the causal link between these multiple isotopic tracers and the mechanisms of Cr stripping into carbonates has to be further investigated in detail, the first indications from this study point to a potentially promising use of stable Cr isotopes in organic-rich carbonates to monitor fluctuations of atmospheric oxygen, particularly over the Neoproterozoic and Phanerozoic ice age periods. E.C. Berna et al. (2010) Cr stable isotopes as indicators of Cr

  12. miR-29c-3p promotes senescence of human mesenchymal stem cells by targeting CNOT6 through p53-p21 and p16-pRB pathways.

    Science.gov (United States)

    Shang, Jin; Yao, Yuan; Fan, Xin; Shangguan, Lei; Li, Jie; Liu, Huan; Zhou, Yue

    2016-04-01

    Mesenchymal stem cells (MSCs) are important seed cells for tissue engineering and are promising targets for cell-based therapies. However, the replicative senescence of MSCs during in vitro culture limits their research and clinical applications. The molecular mechanisms underlying the replicative senescence of MSCs are not fully understood. Evidence suggests that miRNAs play important roles in replicative senescence. A microarray analysis found that the miR-29c-3p level was significantly increased during the MSC senescence process. In our study, we investigated the roles of miR-29c-3p in senescence of MSCs. We cultured MSCs for long periods of time, up and down-regulated the miR-29c-3p expression in MSCs, and examined the senescent phenotype changes. The over-expression of miR-29c-3p led to enhanced senescence-associated-β-galactosidase (SA-β-gal) staining, senescence associated secretory phenotype (SASP), senescence associated heterochromatic foci (SAHF), reduced proliferation ability, retarded osteogenic differentiation and corresponding changes in senescence markers, whereas the miR-29c-3p down-regulation had the opposite results. Dual-luciferase reporter assays demonstrated that CNOT6 is the target gene of miR-29c-3p. Knockdown of CNOT6 confirmed its inhibitory effects on the senescence of MSCs. In addition, Western blot results showed that both the p53-p21 and the p16-pRB pathways were activated during the miR-29c-3p-induced senescence of MSCs. In conclusion, our results demonstrate that miR-29c-3p promotes the senescence of MSCs by targeting CNOT6 through p53-p21 and p16-pRB pathways and highlight the contribution of post-transcriptional regulation to stem cell senescence.

  13. Chromium(III) -- chromium(VI) interconversions in seawater

    NARCIS (Netherlands)

    Weijden, C.H. van der; Reith, M.

    1982-01-01

    The stable form of dissolved chromium in oxygenated seawater is Cr(VI). But Cr(III)-species are also present at an analytically significant level. It is shown that Cr(III) is oxidized only slowly by dissolved oxygen, and that manganese oxide is a strong catalyst for such oxidation. However, the low

  14. p53 Acetylation: Regulation and Consequences

    Energy Technology Data Exchange (ETDEWEB)

    Reed, Sara M. [Department of Pharmacology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Medical Scientist Training Program, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Quelle, Dawn E., E-mail: dawn-quelle@uiowa.edu [Department of Pharmacology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Medical Scientist Training Program, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Department of Pathology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States)

    2014-12-23

    Post-translational modifications of p53 are critical in modulating its tumor suppressive functions. Ubiquitylation, for example, plays a major role in dictating p53 stability, subcellular localization and transcriptional vs. non-transcriptional activities. Less is known about p53 acetylation. It has been shown to govern p53 transcriptional activity, selection of growth inhibitory vs. apoptotic gene targets, and biological outcomes in response to diverse cellular insults. Yet recent in vivo evidence from mouse models questions the importance of p53 acetylation (at least at certain sites) as well as canonical p53 functions (cell cycle arrest, senescence and apoptosis) to tumor suppression. This review discusses the cumulative findings regarding p53 acetylation, with a focus on the acetyltransferases that modify p53 and the mechanisms regulating their activity. We also evaluate what is known regarding the influence of other post-translational modifications of p53 on its acetylation, and conclude with the current outlook on how p53 acetylation affects tumor suppression. Due to redundancies in p53 control and growing understanding that individual modifications largely fine-tune p53 activity rather than switch it on or off, many questions still remain about the physiological importance of p53 acetylation to its role in preventing cancer.

  15. Co-targeting hexokinase 2-mediated Warburg effect and ULK1-dependent autophagy suppresses tumor growth of PTEN- and TP53-deficiency-driven castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2016-05-01

    Full Text Available Currently, no therapeutic options exist for castration-resistant prostate cancer (CRPC patients who have developed resistance to the second generation anti-androgen receptor (AR axis therapy. Here we report that co-deletion of Pten and p53 in murine prostate epithelium, often observed in human CRPC, leads to AR-independent CRPC and thus confers de novo resistance to second generation androgen deprivation therapy (ADT in multiple independent yet complementary preclinical mouse models. In contrast, mechanism-driven co-targeting hexokinase 2 (HK2-mediated Warburg effect with 2-deoxyglucose (2-DG and ULK1-dependent autophagy with chloroquine (CQ selectively kills cancer cells through intrinsic apoptosis to cause tumor regression in xenograft, leads to a near-complete tumor suppression and remarkably extends survival in Pten−/p53-deficiency-driven CRPC mouse model. Mechanistically, 2-DG causes AMPK phosphorylation, which in turn inhibits mTORC1-S6K1 translation signaling to preferentially block anti-apoptotic protein MCL-l synthesis to prime mitochondria-dependent apoptosis while simultaneously activates ULK1-driven autophagy for cell survival to counteract the apoptotic action of anti-Warburg effect. Accordingly, inhibition of autophagy with CQ sensitizes cancer cells to apoptosis upon 2-DG challenge. Given that 2-DG is recommended for phase II clinical trials for prostate cancer and CQ has been clinically used as an anti-malaria drug for many decades, the preclinical results from our proof-of-principle studies in vivo are imminently translatable to clinical trials to evaluate the therapeutic efficacy by the combination modality for a subset of currently incurable CRPC harboring PTEN and TP53 mutations.

  16. Study on anaerobic treatment of wastewater containing hexavalent chromium*

    OpenAIRE

    Xu, Yan-Bin; Xiao, Hua-hua; Sun, Shui-yu

    2005-01-01

    A self-made anaerobic bio-filter bed which was inoculated with special sludge showed high efficiency in removing hexavalent chromium. When pump flow was 47 ml/min and CODCr of wastewater was about 140 mg/L, it took 4 h to decrease the Cr6+ concentrations from about 60 mg/L to under 0.5 mg/L, compared with 14 h without carbon source addition. Cr6+ concentrations ranged from 64.66 mg/L to 75.53 mg/L, the system efficiency was excellent. When Cr6+ concentration reached 95.47 mg/L, the treatment ...

  17. Opto-electronic properties of chromium doped indium-tin-oxide films deposited at room temperature

    International Nuclear Information System (INIS)

    Indium-tin-oxide (ITO) doped chromium films were deposited on Corning 7059 glass prepared by radio frequency (RF) magnetron sputtering under various levels of sputtering power for the chromium target. Experimental results show that the surface roughness slightly decreases by co-sputtering Cr. The pure ITO films deposited at room temperature were amorphous-like. At 15 W of chromium target power, the structure of ITO: Cr film mainly consists of (2 2 2) crystallization plane, with minority of (2 1 1), (4 4 0), (6 6 2) crystallization planes. The carrier concentration of the ITO films increases with increasing the doping of chromium, however the mobility of the carrier decreases. When the sputtering power of the chromium target is at 7.5 W, there has a maximum carrier mobility of 27.3 cm2 V -1 s -1, minimum carrier concentration of 2.47 x 1020 cm-3, and lowest resistivity of 7.32 x 10-4 Ω cm. The transmittance of all the chromium doped ITO films at the 300-800 nm wavelength region in this experiment can reach up to 70-85%. In addition, the blue shift of UV-Vis spectrum is not observed with the increase of carrier concentration

  18. Status quo of p53 in the treatment of tumors.

    Science.gov (United States)

    Guan, Yong-Song; He, Qing; Zou, Qing

    2016-10-01

    The p53 gene is pivotal for oncogenesis in a combination of mutations in oncogenes and antioncogenes. The ubiquitous loss of the p53 pathway in human cancers has generated considerable interest in developing p53-targeted cancer therapies, but current ideas and approaches targeting p53 are conflicting. Current researches focus on cancer-selective drugs with therapeutic strategies that both activate and inhibit p53. As p53 is ubiquitously lost in human cancers, the strategy of exogenous p53 addition is reasonable. However, p53 acts not equally in all cell types; thus, individualized p53 therapy is the direction of future research. To clarify the controversies on p53 for improvement of future antitumor studies, the review focuses on the available technological protocols, including their advantages and limitations in terms of future therapeutic use of p53 in the management of tumors.

  19. Analysis list: Trp53 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Trp53 Embryo,Embryonic fibroblast + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Trp53....1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Trp53.5.tsv http://dbarchive.bi...osciencedbc.jp/kyushu-u/mm9/target/Trp53.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Trp53.Em...bryo.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Trp53.Embryonic_fibr

  20. Determination of chromium combined with DNA, RNA and protein in chromium-rich brewer's yeast

    International Nuclear Information System (INIS)

    The contents of chromium in the DNA, RNA and protein fractions separated from chromium-rich and normal brewer's yeast were determined with the neutron activation analysis in order to study the combination of Cr with DNA, RNA and protein in chromium-rich brewer's yeast. The results showed that the extracting rats and concentrations of DNA, RNA and protein had no significant difference in two types of yeast, but the chromium contents of DNA, RNA and protein in the chromium-rich yeast were significantly higher than those in the normal. In addition, the content of chromium in DNA was much higher than that in RNA and protein, which indicated that the inorganic chromium compounds entered into the yeast cell, during the yeast cultivation in the culture medium containing chromium were converted into organic chromium compounds combined with DNA, RNA and protein

  1. Study on anaerobic treatment of wastewater containing hexavalent chromium.

    Science.gov (United States)

    Xu, Yan-bin; Xiao, Hua-hua; Sun, Shui-yu

    2005-06-01

    A self-made anaerobic bio-filter bed which was inoculated with special sludge showed high efficiency in removing hexavalent chromium. When pump flow was 47 ml/min and COD(Cr) of wastewater was about 140 mg/L, it took 4 h to decrease the Cr6+ concentrations from about 60 mg/L to under 0.5 mg/L, compared with 14 h without carbon source addition. Cr6+ concentrations ranged from 64.66 mg/L to 75.53 mg/L, the system efficiency was excellent. When Cr6+ concentration reached 95.47 mg/L, the treatment time was prolonged to 7.5 h. Compared with the contrast system, the system with trace metals showed clear superiority in that the Cr6+ removal rate increased by 21.26%. Some analyses also showed that hexavalent chromium could probably be bio-reduced to trivalent chromium, and that as a result, the chrome hydroxide sediment was formed on the surface of microorganisms.

  2. Study on anaerobic treatment of wastewater containing hexavalent chromium*

    Science.gov (United States)

    Xu, Yan-bin; Xiao, Hua-hua; Sun, Shui-yu

    2005-01-01

    A self-made anaerobic bio-filter bed which was inoculated with special sludge showed high efficiency in removing hexavalent chromium. When pump flow was 47 ml/min and CODCr of wastewater was about 140 mg/L, it took 4 h to decrease the Cr6+ concentrations from about 60 mg/L to under 0.5 mg/L, compared with 14 h without carbon source addition. Cr6+ concentrations ranged from 64.66 mg/L to 75.53 mg/L, the system efficiency was excellent. When Cr6+ concentration reached 95.47 mg/L, the treatment time was prolonged to 7.5 h. Compared with the contrast system, the system with trace metals showed clear superiority in that the Cr6+ removal rate increased by 21.26%. Some analyses also showed that hexavalent chromium could probably be bio-reduced to trivalent chromium, and that as a result, the chrome hydroxide sediment was formed on the surface of microorganisms. PMID:15909347

  3. Study on anaerobic treatment of wastewater containing hexavalent chromium

    Institute of Scientific and Technical Information of China (English)

    XU Yan-bin; XIAO Hua-hua; SUN Shui-yu

    2005-01-01

    A self-made anaerobic bio-filter bed which was inoculated with special sludge showed high efficiency in removing hexavalent chromium. When pump flow was 47 ml/min and CODCr ofwastewater was about 140 mg/L, it took 4 h to decrease the Cr6+ concentrations from about 60 mg/L to under 0.5 mg/L, compared with 14 h without carbon source addition. Cr6+ concentrations ranged from 64.66 mg/L to 75.53 mg/L, the system efficiency was excellent. When Cr6+ concentration reached 95.47 mg/L,the treatment time was prolonged to 7.5 h. Compared with the contrast system, the system with trace metals showed clear superiority in that the Cr6+ removal rate increased by 21.26%. Some analyses also showed that hexavalent chromium could probably be bio-reduced to trivalent chromium, and that as a result, the chrome hydroxide sediment was formed on the surface of microorganisms.

  4. Synthesis of chromium containing pigments from chromium galvanic sludges.

    Science.gov (United States)

    Andreola, F; Barbieri, L; Bondioli, F; Cannio, M; Ferrari, A M; Lancellotti, I

    2008-08-15

    In this work the screening results of the scientific activity conducted on laboratory scale to valorise chromium(III) contained in the galvanic sludge as chromium precursor for ceramic pigments are reported. The valorisation of this waste as a secondary raw material (SRM) is obtained by achievement of thermal and chemical stable crystal structures able to color ceramic material. Two different pigments pink CaCr(0.04)Sn(0.97)SiO(5) and green Ca(3)Cr(2)(SiO(4))(3) were synthesized by solid-state reactions using dried Cr sludge as chromium oxide precursor. The obtained pigments were characterized by X-ray diffraction and SEM analysis. Furthermore the color developed in a suitable ceramic glaze was investigated in comparison with the color developed by the pigments prepared from pure Cr(2)O(3). The characterization carried out corroborates the thermal and chemical stability of the synthesized pigments and, especially for the Cr-Sn pink pigment, the powders develop an intense color that is very similar to the color developed by the pigments obtained starting from pure Cr(2)O(3). PMID:18289775

  5. Synthesis of chromium containing pigments from chromium galvanic sludges

    Energy Technology Data Exchange (ETDEWEB)

    Andreola, F.; Barbieri, L. [Dipartimento di Ingegneria dei Materiali e dell' Ambiente, Universita di Modena e Reggio Emilia, Via Vignolese 905, 41100 Modena (Italy); Bondioli, F. [Dipartimento di Ingegneria dei Materiali e dell' Ambiente, Universita di Modena e Reggio Emilia, Via Vignolese 905, 41100 Modena (Italy)], E-mail: bondioli.federica@unimore.it; Cannio, M. [Dipartimento di Ingegneria dei Materiali e dell' Ambiente, Universita di Modena e Reggio Emilia, Via Vignolese 905, 41100 Modena (Italy); Ferrari, A.M. [Dipartimento di Scienza e Metodi dell' Ingegneria, Universita di Modena e Reggio Emilia, Viale Amendola 2, 42100 Reggio Emilia (Italy); Lancellotti, I. [Dipartimento di Ingegneria dei Materiali e dell' Ambiente, Universita di Modena e Reggio Emilia, Via Vignolese 905, 41100 Modena (Italy)

    2008-08-15

    In this work the screening results of the scientific activity conducted on laboratory scale to valorise chromium(III) contained in the galvanic sludge as chromium precursor for ceramic pigments are reported. The valorisation of this waste as a secondary raw material (SRM) is obtained by achievement of thermal and chemical stable crystal structures able to color ceramic material. Two different pigments pink CaCr{sub 0.04}Sn{sub 0.97}SiO{sub 5} and green Ca{sub 3}Cr{sub 2}(SiO{sub 4}){sub 3} were synthesized by solid-state reactions using dried Cr sludge as chromium oxide precursor. The obtained pigments were characterized by X-ray diffraction and SEM analysis. Furthermore the color developed in a suitable ceramic glaze was investigated in comparison with the color developed by the pigments prepared from pure Cr{sub 2}O{sub 3}. The characterization carried out corroborates the thermal and chemical stability of the synthesized pigments and, especially for the Cr-Sn pink pigment, the powders develop an intense color that is very similar to the color developed by the pigments obtained starting from pure Cr{sub 2}O{sub 3}.

  6. Tissues and urinary chromium concentrations in rats fed high-chromium diets

    International Nuclear Information System (INIS)

    Complete text of publication follows. Chromium is an essential trace elements and enhances the function of insulin as a form of chromodulin. In the subjects with a certain type of diabetics, 200 to 1,000 μg/d of chromium is administered to reduced the symptoms of diabetics. However, although there are not any health-promotive effects of chromium-administration in healthy subjects, various types of chromium supplements are commercially available in many countries; the adverse effects caused by an excessive chromium intake are feared. In the present study, to clarify the tolerable upper limit of chromium, tissue and urinary chromium concentrations, liver function and iron status were examined in rats fed high-chromium diets. Thirty-six male 4-weeks Wistar rats were divided into six groups and fed casein-based diets containing 1, 10 or 100 μg/g of chromium as chromium chloride (CrCl3) or chromium picolinate (CrPic) for 4 weeks. After the feeding, chromium concentrations in liver, kidney, small intestine and tibia were determined by inductively coupled plasma-mass spectrometry. In addition, urine samples were collected on 3rd to 4th week and their chromium concentrations were also determined. Chromium concentrations in liver, kidney, small intestine and tibia were elevated with increase of dietary chromium concentration. Urinary chromium excretion was also elevated with the increase of dietary chromium and the rate of urinary chromium excretion was less than 2% to dietary chromium intake in all the experimental groups. In the administration of 100 μg/g of chromium, rats given CrCl3 showed significantly higher tibia chromium concentration and lower urinary chromium excretion than those given CrPic. There were not any differences in iron status among the experimental groups. Activities of serum aspartate aminotransferase and alanine aminotransferase in rats fed diet containing 100 μg/g of chromium as CrPic were significantly higher than those in rats fed other diets.

  7. Soils contaminated with hexavalent chromium

    OpenAIRE

    Fonseca, Bruna Catarina da Silva

    2011-01-01

    Tese de doutoramento em Engenharia Química e Biológica The interest in environmental soil science has been growing in the last years due to the continuous degradation of this major natural resource. With this in mind, and because chromium and lead are two of the most toxic heavy metals frequently detected as soil contaminants in the Portuguese territory, the study and development of few remediation techniques and the indissociable description of the sorption and migration of...

  8. Simultaneous determination of chromium(III) and chromium(VI) in aqueous solutions by ion chromatography and chemiluminescence detection

    DEFF Research Database (Denmark)

    Gammelgaard, Bente; Jøns, O; Nielsen, B

    1992-01-01

    A method for the simultaneous determination of chromium(iii) and chromium(vi) in a flow system based on chemiluminescence was developed. A Dionex cation-exchange guard column was used to separate chromium(iii) from chromium(vi), and chromium(vi) was reduced by potassium sulfite, whereupon both sp...

  9. Controlling the Mdm2-Mdmx-p53 Circuit

    OpenAIRE

    Waning, David L.; Lehman, Jason A.; Batuello, Christopher N.; Mayo, Lindsey D.

    2010-01-01

    The p53 tumor suppressor is a key protein in maintaining the integrity of the genome by inducing either cell cycle arrest or apoptosis following cellular stress signals. Two human family members, Mdm2 and Mdmx, are primarily responsible for inactivating p53 transcription and targeting p53 protein for ubiquitin-mediated degradation. In response to genotoxic stress, post-translational modifications to p53, Mdm2 and Mdmx stabilize and activate p53. The role that phosphorylation of these molecule...

  10. α-Mangostin-encapsulated PLGA nanoparticles inhibit pancreatic carcinogenesis by targeting cancer stem cells in human, and transgenic (KrasG12D, and KrasG12D/tp53R270H) mice

    Science.gov (United States)

    Verma, Raj Kumar; Yu, Wei; Shrivastava, Anju; Shankar, Sharmila; Srivastava, Rakesh K.

    2016-01-01

    Activation of sonic hedgehog (Shh) in cancer stem cell (CSC) has been demonstrated with aggressiveness of pancreatic cancer. In order to enhance the biological activity of α-mangostin, we formulated mangostin-encapsulated PLGA nanoparticles (Mang-NPs) and examined the molecular mechanisms by which they inhibit human and KC mice (PdxCre;LSL-KrasG12D) pancreatic CSC characteristics in vitro, and pancreatic carcinogenesis in KPC (PdxCre;LSLKrasG12D;LSL-Trp53R172H) mice. Mang-NPs inhibited human and KrasG12D mice pancreatic CSC characteristics in vitro. Mang-NPs also inhibited EMT by up-regulating E-cadherin and inhibiting N-cadherin and transcription factors Slug, and pluripotency maintaining factors Nanog, c-Myc, and Oct4. Furthermore, Mang-NPs inhibited the components of Shh pathway and Gli targets. In vivo, Mang-NPs inhibited the progression of pancreatic intraneoplasia to pancreatic ductal adenocarcinoma and liver metastasis in KPC mice. The inhibitory effects of Mang-NPs on carcinogenesis in KPC mice were associated with downregulation of pluripotency maintaining factors (c-Myc, Nanog and Oct4), stem cell markers (CD24 and CD133), components of Shh pathway (Gli1, Gli2, Patched1/2, and Smoothened), Gli targets (Bcl-2, XIAP and Cyclin D1), and EMT markers and transcription factors (N-cadherin, Slug, Snail and Zeb1), and upregulation of E-cadherin. Overall, our data suggest that Mang-NPs can inhibit pancreatic cancer growth, development and metastasis by targeting Shh pathway. PMID:27624879

  11. Inoculation of chromium white cast iron

    Directory of Open Access Journals (Sweden)

    D. Kopyciński

    2009-01-01

    Full Text Available It has been proved that an addition of boron carbide introduced as an inoculant to the chromium white cast iron changes the structureof castings. Castings after inoculation revealed a different structure with numerous grains. Primary precipitates of chromium carbide also appeared, reducing the mechanical properties of as-cast parts. Properly established heat treatment regime makes chromium iron castings regain their, originally high, mechanical properties.

  12. REMOVAL OF HEXAVALENT CHROMIUM FROM DRINKING WATER

    OpenAIRE

    A. R. Asgari ، F. Vaezi ، S. Nasseri ، O. Dördelmann ، A. H. Mahvi ، E. Dehghani Fard

    2008-01-01

    Removal of chromium can be accomplished by various methods but none of them is cost-effective in meeting drinking water standards. For this study, granular ferric hydroxide was used as adsorbent for removal of hexavalent chromium. Besides, the effects of changing contact time, pH and concentrations of competitive anions were determined for different amounts of granular ferric hydroxide. It was found that granular ferric hydroxide has a high capacity for adsorption of hexavalent chromium from ...

  13. Analysis list: lin-53 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available lin-53 Larvae + ce10 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/lin-53....1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/lin-53.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/lin...-53.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/lin-53.Larvae.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/Larvae.gml ...

  14. Permeation of chromium salts through human skin in vitro

    DEFF Research Database (Denmark)

    Gammelgaard, Bente; Fullerton, A; Avnstorp, C;

    1992-01-01

    of the dichromate solution. Chromium skin levels increased with increasing concentrations of applied chromium salts up to 0.034 M Cr. The amount of chromium in recipient phase and skin layers increased with increasing pH when the applied solution contained potassium dichromate. This was ascribed to a decreased skin...... barrier function of the skin. The amount of chromium found in all skin layers after application of chromium chloride decreased with increasing pH due to lower solubility of the salt. The % of chromium found in the recipient phase as chromium(VI) increased with increasing total chromium concentration...... indicating a limited reduction ability of the skin in vitro....

  15. Chromium in aqueous nitrate plutonium process streams: Corrosion of 316 stainless steel and chromium speciation

    International Nuclear Information System (INIS)

    This study was undertaken to determine if chromium(+6) could exist in plutonium process solutions under normal operating conditions. Four individual reactions were studied: the rate of dissolution of stainless steel, which is the principal source of chromium in process solutions; the rate of oxidation of chromium(+3) to chromium(+6) by nitric acid; and the reduction of chromium(+6) back to chromium(+3) by reaction with stainless steel and with oxalic acid. The stainless steel corrosion rate was found to increase with increasing nitric acid concentration, increasing hydrofluoric acid concentration, and increasing temperature. Oxidation of chromium(+3) to chromium(+6) was negligible at room temperature and only became significant in hot concentrated nitric acid. The rate of reduction of chromium(+6) back to chromium(+3) by reaction with stainless steel or oxalic acid was found to be much greater than the rate of the reverse oxidation reaction. Based on these findings and taking into account normal operating conditions, it was determined that although there would be considerable chromium in plutonium process streams it would rarely be found in the (+6) oxidation state and would not exist in the (+6) state in the final process waste solutions

  16. The influence of substrate temperature on the tribo- mechanical properties of chromium nitride thin films

    Science.gov (United States)

    Merie, V. V.; Negrea, G.; Modi, E.

    2016-08-01

    Different nitrides such as titanium nitride, chromium nitride and so on are used in a widespread range of applications such as cutting tools, medical implants, and microelectromechanical devices and all that due to their mechanical, physical and chemical properties. The aim of this study is to obtain chromium nitride thin films and to characterize them by atomic force microscopy investigations. The chromium nitride thin films were deposited by reactive magnetron sputtering on silicon substrates. During the deposition process, the discharge current, the argon and nitrogen flows, the pressure inside the chamber and the deposition time were kept constant. A chromium target with a purity of 99.95 % was used. Some of the films were deposited after a chromium buffer layer was previously deposited on the silicon substrate. The deposition was carried out when substrate temperature was at room temperature, at 300 and 500°C respectively. Once the films were deposited, atomic force microscopy investigations were performed in order to emphasize the influence of the substrate temperature on the topographical, mechanical and tribological characteristics. The results pointed out an important influence of the substrate temperature on topographical, mechanical and tribological properties of the investigated chromium nitride thin films.

  17. Electrodeposition of chromium from trivalent chromium urea bath containing sulfate and chloride

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The reduction of Cr( Ⅲ) to Cr( Ⅱ ) on copper electrode in trivalent chromium urea bath containing chromium sulfate and chromium chloride as chromium source has been investigated by potentiodynamic sweep. The transfer coefficient α for reduction of Cr( Ⅲ ) to Cr( Ⅱ ) on copper electrode was calculated as 0.46. The reduction is a quasi-reversible process. J-t responses at different potential steps showed that the generation and adsorption characteristics of carboxylate bridged oligomer are relevant to cathode potential. The interface behavior between electrode and solution for Cr( Ⅲ ) complex is a critical factor influencing sustained electrode position of chromium. The hypotheses of the electro-inducing polymerization of Cr( Ⅲ ) was proposed. The potential scope in which sustained chromium deposits can be prepared is from- 1.3 V to- 1.7 V (vs SCE) in the urea bath. Bright chromium deposits with thickness of 30 μm can be prepared in the bath.

  18. Alkane dehydrogenation over supported chromium oxide catalysts

    NARCIS (Netherlands)

    Weckhuysen, B.M.; Schoonheydt, R.A.

    1999-01-01

    The dehydrogenation of alkanes over supported chromium oxide catalysts in the absence of oxygen is of high interest for the industrial production of propene and isobutene. In this review, a critical overview is given of the current knowledge nowadays available about chromium-based dehydrogenation ca

  19. Toxicity of depleted uranium complexes is independent of p53 activity

    OpenAIRE

    Heintze, Ellie; Aguilera, Camille; Davis, Malia; Fricker, Avery; Li, Qiang; Martinez, Jesse; Matthew J. Gage

    2010-01-01

    The p53 tumor suppressor protein is one of the key checkpoints in cellular response to a variety of stress mechanisms, including exposure to various toxic metal complexes. Previous studies have demonstrated that arsenic and chromium complexes are able to activate p53, but there is a dearth of data investigating whether uranium complexes exhibit similar effects. The use of depleted uranium (DU) has increased in recent years, raising concern about DU’s potential carcinogenic effects. Previous s...

  20. [Bioremediation of chromium (VI) contaminated site by reduction and microbial stabilization of chromium].

    Science.gov (United States)

    Zheng, Jia-Chuan; Zhang, Jian-Rong; Liu, Xi-Wen; Xu, Qian; Shi, Wei-Lin

    2014-10-01

    Chromium (VI) contaminated soil samples were collected from a chemical plant in Suzhou. Firstly, the reduced soil was prepared by adding reagent (Stone-sulfure reagent) into polluted soil to transfer most chromium (VI) into chromium (III), then a nutrient solution was introduced into the reduced soil, and the stabilized soil was obtained after 60 days culturing. The chromium (VI) content of the three kinds of soil was analyzed. The results showed that the chromium (VI) content in toxicity characteristic leaching liquid (TCLL) dropped by 96. 8% (from 8.26 mg · L(-1) to 0.26 mg · L(-1)), and the total chromium content dropped by 95.7% (from 14.66 mg · L(-1) to 0.63 mg · L(-1)) after bioremediation in 5% nutrient solution. Additionally, the durability of chromium stabilization was tested by potassium permanganate oxidation and sterilization of microbe-treated soil. After oxidation, the chromium (VI) content in TCLL of the reduced soil was increased from 8.26 mg · L(-1) to 14.68 mg · L(-1). However, the content after bioremediation was decreased to 2.68 mg · L(-1). The results of sterilization demonstrated that the death of microbe had no significant effect on the stabilization of chromium. Consequently, the research in this paper demonstrated the feasibility of bioremediation of chromium (VI) polluted soil through reduction followed by stabilization/soilidification, and provided a technique with low cost but high efficiency.

  1. Low-chromium reduced-activation chromium-tungsten steels

    Energy Technology Data Exchange (ETDEWEB)

    Klueh, R.L.; Alexander, D.J.; Maziasz, P.J. [Oak Ridge National Lab., TN (United States)

    1996-10-01

    Bainitic microstructures formed during continuous cooling can differ from classical upper and lower bainite formed during isothermal transformation. Two types of non-classical bainite were observed depending on the cooling rate: carbide-free acicular bainite at rapid cooling rates and granular bainite at slower cooling rates. The Charpy impact toughness of the acicular ferrite was found to be considerably better than for the granular bainite. It was postulated that alloying to improve the hardenability of the steel would promote the formation of acicular bainite, just as increasing the cooling rate does. To test this, chromium and tungsten were added to the 2 1/4Cr-2W and 2 1/4Cr-2WV steel compositions to increase their hardenability, and the microstructures and mechanical properties were examined.

  2. Bainitic chromium-tungsten steels with 3 pct chromium

    International Nuclear Information System (INIS)

    Previous work on 3Cr-1.5MoV (nominally Fe-3Cr-2.5Mo-0.25V-0.1C), 2.25Cr-2W (Fe-2.25Cr-2W-0.1C), and 2.25Cr-2WV (Fe-2.25Cr-2W-0.25V-0.1C) steels indicated that the impact toughness of these steels depended on the microstructure of the bainite formed during continuous cooling from the austenization temperature. Microstructures formed during continuous cooling can differ from classical upper and lower bainite formed during isothermal transformation. Two types of nonclassical microstructures were observed depending on the cooling rate: carbide-free acicular bainite at rapid cooling rates and granular bainite at slower cooling rates. The Charpy impact toughness of the acicular ferrite was considerably better than for the granular bainite. It was postulated that alloying to improve the hardenability of the steel would promote the formation of acicular bainite, just as increasing the cooling rate does. To test this, chromium and tungsten were added to the 2.25Cr-2W and 2.25Cr-2WV steel compositions to increase their hardenability. Charpy testing indicated that the new 3Cr-W and 3Cr-WV steels had improved impact toughness, as demonstrated by lower ductile-brittle transition temperatures and higher upper-shelf energies. This improvement occurred with less tempering than was necessary to achieve similar toughness for the 2.25Cr steels and for high-chromium (9 to 12 pct Cr) Cr-W and Cr-Mo steels

  3. Chromium Isotopes Record Fluctuations in Precambrian Biospheric Oxygenation

    Science.gov (United States)

    Frei, R.; Gaucher, C.; Poulton, S. W.; Canfield, D. E.

    2009-12-01

    There is a direct relationship between life, oxygen, and the surface chemistry of the Earth. Geochemical data suggest that oxygenation of the Earth's atmosphere occurred in two broad steps, near the beginning and the end of the Proterozoic Eon (2500 to 542 million years ago), but the details of this history are unclear. The geochemical behaviour of chromium (Cr) is highly sensitive to the redox state of the surface environment as oxidative weathering processes produce the oxidised hexavalent [Cr(VI)] form. Oxidation of reduced trivaltent [Cr(III)] chromium on land is accompanied by an isotopic fractionation, leading to enrichment of the mobile hexavalent form in the heavier isotope. The fractionated Cr isotope signature is then tranfered by riverine transport to the sea. Here, we use Cr stable isotopes from banded iron formations (BIFs) to track the presence of Cr(VI) in Precambrian oceans, providing a time-resolved picture of the oxygenation history of Earth’s atmosphere-hydrosphere system. Fractionated Cr isotopes indicate the accumulation of Cr(VI) in ocean surface waters ~2.8 to 2.6 billion years (Gyr) ago and a likely transient elevation in atmospheric and surface ocean oxygen prior to the first great rise of oxygen 2.45-2.2 Gyr ago (the Great Oxidation Event; GOE). In contrast, Cr isotopes in ~1.88 Gyr old BIFs are not fractionated, indicating a major decline in atmospheric oxygen and demonstrating that the GOE did not lead to a unidirectional stepwise increase in atmospheric oxygen. In the late Neoproterozoic, ~800 to 542 million years (Myr) ago, we observe strong positive fractionations in Cr isotopes (δ53Cr up to +4.9 ‰) providing independent support for increased surface oxygenation at this time. This may have stimulated rapid evolution of macroscopic multicellular life. Our chromium isotope data thus provide new insights into the oxygenation history of the Earth, and highlight its use as a powerful redox tracer in aquatic systems.

  4. Chromium

    Science.gov (United States)

    ... 6+), a toxic form that results from industrial pollution. This fact sheet focuses exclusively on trivalent (3+) ... 1 medium 1 Banana, 1 medium 1 Green beans, ½ cup 1 What are recommended intakes of ...

  5. Reproductive toxicological aspects of chromium in males

    International Nuclear Information System (INIS)

    To expand our present understanding of the effects of chromium on male fertility a number of studies were designed to achieve this through the use of chromium intoxicated experimental animals and through investigation of sexual hormones and sperm quality in welders. Also in view of the lack of an experimental model for effects of noxious substance on the epididymal spermatozoa the main objectives of the series of studies reviewed here were: A. To establish a model for evaluation of epididymal sperm count and motility in the rat. B. To investigate and compare the effects of tri- and hexavalent chromium on epididymal spermatozoa. Further to describe the effects of low-dose long-time exposure of rats to the most toxicological interesting chromium oxidative state - hexavalent chromium. C. By the use of autoradiography and γ-countinuing to expand the present knowledge on the distribution of chromium in the body with special reference to the male reproductive organs. D. To describe the effects of exposure to hexavalent chromium in welding fume on levels of sexual hormones and semen parameters in welders. (EG)

  6. Analysis list: TP53 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available encedbc.jp/kyushu-u/hg19/target/TP53.1.tsv http://dbarchive.biosciencedbc.jp/kyushu...-u/hg19/target/TP53.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/TP53.10.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/TP53.Blood.tsv,http://dbarchive.bioscienced...bc.jp/kyushu-u/hg19/colo/TP53.Bone.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/TP53.Breast.tsv,http://dbarchive.bioscien...cedbc.jp/kyushu-u/hg19/colo/TP53.Digestive_tract.tsv,http://dbarchive.biosciencedbc

  7. Synthesis of Chromium (Ⅲ) 5-aminosalicylate

    Institute of Scientific and Technical Information of China (English)

    LI Wei; HAO Er-jun; JIANG Yu-qin

    2004-01-01

    As we all known that diabetes is a chronic disease with major health consequences.Research has revealed that the occurrence of diabetes have great thing to do with the chromium deficient. Almost 40 years after the first report of glucose tolerance factor(GTF) [1], no conclusive evidence for an isolable ,biologically active form of chromium exited. Three materials have been proposed to be the biologically active form of chromium: "glucose tolerance factor", chromium Picolinate and low-molecular-weight chromium-binding substance (LWMCr) [2] . So there is potential for the design of new chromium drugs .5-Aminosalicylic acid (5-ASA) is identified as an active component in the therapy of inflammatory bowel disease (IBD) such as Crohn's disease and ulcerative colitis . The therapeutic action of 5-ASA is believed to be coupled to its ability to act as a free radical scavenger [3-4],acting locally on the inflamed colonic mucosa [5-7]. However, the clinical use of 5-ASA is limited, since orally administered 5-ASA is rapidly and completely absorbed from the upper gastrointestinal tract and therefore the local therapeutic effects of 5-ASA in the colon is hardly expected.In this paper, we report the synthesis of chromium(Ⅲ)5-aminosalicylate from 5-ASA and CrCl3. 6H2O.The synthesis route is as follow:The complex has been characterized by elemental analysis, IR spectra, X-ray powder diffractionand TG-DTA . They indicate that the structure is tris(5-ASA) Chromium . Experiments show that thecomplex has a good activity for supplement tiny dietary chromium, lowering blood glucose levels,lowering serum lipid levels and in creasing lean body mass .

  8. Characteristics of chromium-allergic dermatitis patients prior to regulatory intervention for chromium in leather

    DEFF Research Database (Denmark)

    Bregnbak, David; Thyssen, Jacob P; Zachariae, Claus;

    2014-01-01

    BACKGROUND: Chromium-tanned leather articles currently constitute the most important cause of contact allergy to chromium in Denmark. A regulation on the content of hexavalent chromium in leather was adopted in November 2013 by the EU member states. OBJECTIVES: To characterize patients...... with chromium allergy and their disease, to serve as a baseline for future studies on the potential effect of the new regulation on chromium in leather. METHODS: A questionnaire case-control study was performed on 155 dermatitis patients with positive patch test reactions to potassium dichromate and a matched...... control group of 621 dermatitis patients. Comparisons were made by use of a χ(2) -test and the Mann-Whitney U-test. Logistic regression analyses were used to test for associations. RESULTS: Sixty-six per cent of chromium-allergic patients had a positive history of contact dermatitis caused by leather...

  9. Chromium in leather footwear-risk assessment of chromium allergy and dermatitis

    DEFF Research Database (Denmark)

    Thyssen, Jacob P; Strandesen, Maria; Poulsen, Pia B;

    2012-01-01

    Background. Chromium-tanned leather footwear, which releases >3 ppm hexavalent Cr(VI), may pose a risk of sensitizing and eliciting allergic dermatitis. Objectives. To determine the content and potential release of chromium in leather footwear and to discuss the prevention of chromium contact...... allergy and dermatitis. Methods. Sixty pairs of leather shoes, sandals and boots (20 children's, 20 men's, and 20 women's) were purchased in Copenhagen and examined with X-ray fluorescence spectroscopy. Chromium was extracted according to the International Standard, ISO 17075. The detection level for Cr......(VI) was 3 ppm. Results. Chromium was identified in 95% of leather footwear products, the median content being 1.7% (range 0-3.3%). No association with store category or footwear category was found. A tendency for there to be a higher chromium content in footwear with high prices was shown (p(trend) = 0...

  10. Quaternary structure of the specific p53–DNA complex reveals the mechanism of p53 mutant dominance

    OpenAIRE

    Aramayo, Ricardo; Sherman, Michael B.; Brownless, Kathryne; Lurz, Rudi; Okorokov, Andrei L.; Orlova, Elena V

    2011-01-01

    The p53 tumour suppressor is a transcriptional activator that controls cell fate in response to various stresses. p53 can initiate cell cycle arrest, senescence and/or apoptosis via transactivation of p53 target genes, thus preventing cancer onset. Mutations that impair p53 usually occur in the core domain and negate the p53 sequence-specific DNA binding. Moreover, these mutations exhibit a dominant negative effect on the remaining wild-type p53. Here, we report the cryo electron microscopy s...

  11. Potentiometry: A Chromium (III) -- EDTA Complex

    Science.gov (United States)

    Hoppe, J. I.; Howell, P. J.

    1975-01-01

    Describes an experiment that involves the preparation of a chromium (III)-EDTA compound, a study of its infrared spectrum, and the potentiometric determination of two successive acid dissociation constants. (Author/GS)

  12. AEROSOL BEHAVIOR IN CHROMIUM WASTE INCINERATION

    Institute of Scientific and Technical Information of China (English)

    Suyuan Yu

    2003-01-01

    Cr2O3 is considered as the dominant incineration product during the combustion disposal of chromium waste. A hydrogen/air diffusion flame was employed to simulate the industrial process of incineration. Cr2O3 aerosols were generated inside the flame by the gas phase reaction of chromium and oxygen. Chromium came from the rapid decomposition of chromium hexacarbonyl (Cr(CO)6) at room temperature and was carried into the combustion chamber by hydrogen. Aerosol and clusters can then be easily formed in the flame by nucleation and coagulation. A two dimensional Discrete-Sectional Model (DSM) was adopted to calculate the Cr2O3 aerosol behavior. The experimental measurement method was Dynamic Light Scattering. The numerically predicted results agreed well with those of the experimental measurement. Both results show that the Cr2O3 aerosol size reached about 70 nanometers at the flame top.

  13. Localized Corrosion of Chromium Coated Steel

    NARCIS (Netherlands)

    Zhang, X.; Beentjes, P.; Mol, A.; Terryn, H.

    2006-01-01

    In this paper, we report on the studies of the local corrosion behaviour of chromium-coated ultra low carbon steel in NaCl solution using polarization, electrochemical impedance spectroscopy (EIS) and SVET.

  14. The chromium isotope composition of reducing and oxic marine sediments

    Science.gov (United States)

    Gueguen, Bleuenn; Reinhard, Christopher T.; Algeo, Thomas J.; Peterson, Larry C.; Nielsen, Sune G.; Wang, Xiangli; Rowe, Harry; Planavsky, Noah J.

    2016-07-01

    The chromium (Cr) isotope composition of marine sediments has the potential to provide new insights into the evolution of Earth-surface redox conditions. There are significant but poorly constrained isotope fractionations associated with oxidative subaerial weathering and riverine transport, the major source of seawater Cr, and with partial Cr reduction during burial in marine sediments, the major sink for seawater Cr. A more comprehensive understanding of these processes is needed to establish global Cr isotope mass balance and to gauge the utility of Cr isotopes as a paleoredox proxy. For these purposes, we investigated the Cr isotope composition of reducing sediments from the upwelling zone of the Peru Margin and the deep Cariaco Basin. Chromium is present in marine sediments in both detrital and authigenic phases, and to estimate the isotopic composition of the authigenic fraction, we measured δ53Cr on a weakly acid-leached fraction in addition to the bulk sediment. In an effort to examine potential variability in the Cr isotope composition of the detrital fraction, we also measured δ53Cr on a variety of oxic marine sediments that contain minimal authigenic Cr. The average δ53Cr value of the oxic sediments examined here is -0.05 ± 0.10‰ (2σ, n = 25), which is within the range of δ53Cr values characteristic of the bulk silicate Earth. This implies that uncertainty in estimates of authigenic δ53Cr values based on bulk sediment analyses is mainly linked to estimation of the ratio of Cr in detrital versus authigenic phases, rather than to the Cr-isotopic composition of the detrital pool. Leaches of Cariaco Basin sediments have an average δ53Cr value of +0.38 ± 0.10‰ (2σ, n = 7), which shows no dependency on sample location within the basin and is close to that of Atlantic deepwater Cr (∼+0.5‰). This suggests that authigenic Cr in anoxic sediments may reliably reflect the first-order Cr isotope composition of deepwaters. For Peru Margin samples

  15. Synthesis and Characterization of Chromium Oxide Nanoparticles

    OpenAIRE

    Vivek Sheel Jaswal; Avnish Kumar Arora; Joginder Singh; Mayank Kinger; Vishnu Dev Gupta

    2014-01-01

    Chromium oxide nanoparticles (NPs)have been rapidly synthesized by precipitation method using ammomia as precipitating agent and are characterized by using X-ray Diffraction (XRD), Thermo Gravimetric Analysis (TGA), UV-Visible absorption (UV), Infrared Spectoscopy (IR), Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). XRD studies show that chromium oxide NP is formed as Cr2O3 and it has hexagonal structure. The shape and particle size of the synthesized Cr2O3 NP...

  16. miR-605 joins p53 network to form a p53:miR-605:Mdm2 positive feedback loop in response to stress

    OpenAIRE

    Xiao, Jiening; Lin, Huixian; Luo, Xiaobin; Luo, Xiaoyan; Wang, Zhiguo

    2011-01-01

    Mdm2, a transcriptional target of p53, promotes p53 degradation in a well-established negative feedback loop. Here, microRNA miR-605 is found to break this loop: being induced by p53 in response to stress, and downregulating Mdm2 to promote robust p53 expression.

  17. Standard Specification for Low-Carbon Nickel-Chromium-Molybdenum, Low-Carbon Nickel-Molybdenum-Chromium, Low-Carbon Nickel-Molybdenum-Chromium-Tantalum, Low-Carbon Nickel-Chromium-Molybdenum-Copper, and Low-Carbon Nickel-Chromium-Molybdenum-Tungsten Alloy Rod

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2015-01-01

    Standard Specification for Low-Carbon Nickel-Chromium-Molybdenum, Low-Carbon Nickel-Molybdenum-Chromium, Low-Carbon Nickel-Molybdenum-Chromium-Tantalum, Low-Carbon Nickel-Chromium-Molybdenum-Copper, and Low-Carbon Nickel-Chromium-Molybdenum-Tungsten Alloy Rod

  18. Standard Specification for Low-Carbon Nickel-Chromium-Molybdenum, Low-Carbon Nickel-Chromium-Molybdenum-Copper, Low-Carbon Nickel-Chromium-Molybdenum-Tantalum, Low-Carbon Nickel-Chromium-Molybdenum-Tungsten, and Low-Carbon Nickel-Molybdenum-Chromium Alloy Plate, Sheet, and Strip

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2015-01-01

    Standard Specification for Low-Carbon Nickel-Chromium-Molybdenum, Low-Carbon Nickel-Chromium-Molybdenum-Copper, Low-Carbon Nickel-Chromium-Molybdenum-Tantalum, Low-Carbon Nickel-Chromium-Molybdenum-Tungsten, and Low-Carbon Nickel-Molybdenum-Chromium Alloy Plate, Sheet, and Strip

  19. Bioremediation of chromium solutions and chromium containing wastewaters.

    Science.gov (United States)

    Malaviya, Piyush; Singh, Asha

    2016-08-01

    Cr(VI) represents a serious threat to human health, living resources and ecological system as it is persistent, carcinogenic and toxic, whereas, Cr(III), another stable oxidation state of Cr, is less toxic and can be readily precipitated out of solution. The conventional methods of Cr(VI) removal from wastewaters comprise of chemical reduction followed by chemical precipitation. However, these methods utilize large amounts of chemicals and generate toxic sludge. This necessitates the need for devising an eco-technological strategy that would use the untapped potential of the biological world for remediation of Cr(VI) containing wastewaters. Among several viable approaches, biotransformation of Cr(VI) to relatively non-toxic Cr(III) by chromium resistant bacteria offers an economical- and environment-friendly option for its detoxification. Various studies on use of Cr(VI) tolerant viable bacterial isolates for treatment of Cr(VI) containing solutions and wastewater have been reported. Therefore, a detailed account of mechanisms and processes involved in bioreduction of Cr(VI) from solutions and wastewaters by bacterial isolates are the focus of this review article in addition to a discussion on toxicity of Cr(VI) on bacterial strains and various factors affecting Cr(VI) bioreduction. PMID:25358056

  20. Direct access to macroporous chromium nitride and chromium titanium nitride with inverse opal structure.

    Science.gov (United States)

    Zhao, Weitian; DiSalvo, Francis J

    2015-03-21

    We report a facile synthesis of single-phase, nanocrystalline macroporous chromium nitride and chromium titanium nitride with an inverse opal morphology. The material is characterized using XRD, SEM, HR-TEM/STEM, TGA and XPS. Interconversion of macroporous CrN to Cr2O3 and back to CrN while retaining the inverse opal morphology is also demonstrated.

  1. Diminishing Chromium Use on Combined Chromium-Gambier Tanning Process Upon the Characteristics of Tanned Leather

    Directory of Open Access Journals (Sweden)

    A. Kasim

    2014-04-01

    Full Text Available The research was aimed to investigate the influence of minimizing chromium use on combined chromium-gambier process upon the characteristics of tanned leather. At the first stage of tanning process, chromium was used and in the second stage it was replaced by gambier. The raw material used was dried saline-preserved goat skin. The treatments applied on the tanning process were the different concentrations of chromium ranging from the highest level of 6% to the lowest level of 1% which was then re-tanned by using 8% concentration of gambier. The examination parameters included chemical and physical properties as well as visual investigation on the tanned leather in accordance with SNI-06-0463-1989-A. The result showed that the tanning process by using 2% chromium in the first step and 8% gambier in the second step was a treatment combination producing tanned leather that met the standard. The examination on tanned leather resulted from such treatment showed 56.33% rawhide, 17.45% of bound tannin, 31.22% of tanning level, tensile strength 386.30 kg/cm2, flexibility 31.91%, leather width 1.3 mm, density 0.75 g/cm3, the leather was quite elastic with light brownish color. In conclusion, minimizing the use of chromium in the combined tanning process of chromium and gambier can be implemented to the lowest of 2% chromium concentration and 8% gambier in the first and second step, respectively.

  2. Tumor suppressor p53 and its gain-of-function mutants in cancer

    OpenAIRE

    Liu, Juan; Zhang, Cen; Feng, Zhaohui

    2013-01-01

    Tumor suppressor p53 plays a pivotal role in tumor suppression. p53 is the most frequently mutated gene in cancer. As a transcription factor, p53 mainly exerts its role in tumor suppression through transcriptional regulation of its downstream target genes. Thus, p53 and its target genes form a complex p53 signaling pathway to regulate a wide variety of biological processes to prevent tumorigenesis. Recent studies have revealed that in addition to apoptosis, cell cycle arrest and senescence, p...

  3. Urodele p53 tolerates amino acid changes found in p53 variants linked to human cancer

    Directory of Open Access Journals (Sweden)

    Villiard Éric

    2007-09-01

    Full Text Available Abstract Background Urodele amphibians like the axolotl are unique among vertebrates in their ability to regenerate and their resistance to develop cancers. It is unknown whether these traits are linked at the molecular level. Results Blocking p53 signaling in axolotls using the p53 inhibitor, pifithrin-α, inhibited limb regeneration and the expression of p53 target genes such as Mdm2 and Gadd45, suggesting a link between tumor suppression and regeneration. To understand this relationship we cloned the p53 gene from axolotl. When comparing its sequence with p53 from other organisms, and more specifically human we observed multiple amino acids changes found in human tumors. Phylogenetic analysis of p53 protein sequences from various species is in general agreement with standard vertebrate phylogeny; however, both mice-like rodents and teleost fishes are fast evolving. This leads to long branch attraction resulting in an artefactual basal emergence of these groups in the phylogenetic tree. It is tempting to assume a correlation between certain life style traits (e.g. lifespan and the evolutionary rate of the corresponding p53 sequences. Functional assays of the axolotl p53 in human or axolotl cells using p53 promoter reporters demonstrated a temperature sensitivity (ts, which was further confirmed by performing colony assays at 37°C. In addition, axolotl p53 was capable of efficient transactivation at the Hmd2 promoter but has moderate activity at the p21 promoter. Endogenous axolotl p53 was activated following UV irradiation (100 j/m2 or treatment with an alkylating agent as measured using serine 15 phosphorylation and the expression of the endogenous p53 target Gadd45. Conclusion Urodele p53 may play a role in regeneration and has evolved to contain multiple amino acid changes predicted to render the human protein defective in tumor suppression. Some of these mutations were probably selected to maintain p53 activity at low temperature. However

  4. Lateral stress evolution in chromium sulfide cermets with varying excess chromium

    Science.gov (United States)

    Petel, O. E.; Appleby-Thomas, G. J.; Wood, D. C.; Capozzi, A.; Nabavi, A.; Goroshin, S.; Frost, D. L.; Hazell, P. J.

    2016-04-01

    The shock response of chromium sulfide-chromium, a cermet of potential interest as a matrix material for ballistic applications, has been investigated at two molar ratios. Using a combustion synthesis technique allowed for control of the molar ratio of the material, which was investigated under near-stoichiometric (cermet) and excess chromium (interpenetrating composite) conditions, representing chromium:sulfur molar ratios of 1.15:1 and 4:1, respectively. The compacts were investigated via the plate-impact technique, which allowed the material to be loaded under a one-dimensional state of strain. Embedded manganin stress gauges were employed to monitor the temporal evolution of longitudinal and lateral components of stress in both materials. Comparison of these two components has allowed assessment of the variation of material shear strength both with impact pressure/strain-rate and time for the two molar ratio conditions. The two materials exhibited identical material strength despite variations in their excess chromium contents.

  5. Chemical Variations on the p53 Reactivation Theme

    Directory of Open Access Journals (Sweden)

    Carlos J. A. Ribeiro

    2016-05-01

    Full Text Available Among the tumor suppressor genes, p53 is one of the most studied. It is widely regarded as the “guardian of the genome”, playing a major role in carcinogenesis. In fact, direct inactivation of the TP53 gene occurs in more than 50% of malignancies, and in tumors that retain wild-type p53 status, its function is usually inactivated by overexpression of negative regulators (e.g., MDM2 and MDMX. Hence, restoring p53 function in cancer cells represents a valuable anticancer approach. In this review, we will present an updated overview of the most relevant small molecules developed to restore p53 function in cancer cells through inhibition of the p53-MDMs interaction, or direct targeting of wild-type p53 or mutated p53. In addition, optimization approaches used for the development of small molecules that have entered clinical trials will be presented.

  6. p53CP, a putative p53 competing protein that specifically binds to the consensus p53 DNA binding sites: A third member of the p53 family?

    OpenAIRE

    Bian, Junhui; Sun, Yi

    1997-01-01

    p53 tumor suppressor protein negatively regulates cell growth, mainly through the transactivation of its downstream target genes. As a sequence-specific DNA binding transcription factor, p53 specifically binds to a 20-bp consensus motif 5′-PuPuPuC(A/T) (T/A)GPyPyPyPuPuPuC(A/T)(T/A)GPyPyPy-3′. We have now identified, partially purified, and characterized an additional ≈40-kDa nuclear protein, p53CP (p53 competing protein), that specifically binds to the consensus p53 binding sites found in sev...

  7. The leukemic oncoprotein NPM1-RARA inhibits TP53 activity.

    Science.gov (United States)

    Swaney, Erin M; Chattopadhyay, Anuja; Abecassis, Irina; Rush, Elizabeth A; Redner, Robert L

    2016-08-01

    The variant acute promyelocytic leukemia (APL) translocation t(5;17)(q35;q21) fuses the N-terminus of nucleophosmin (NPM1) to the retinoic acid receptor alpha (RARA). We found that ectopic NPM1-RARA expression decreased TP53 protein levels in target cells. NPM1-RARA impaired TP53-dependent transcription. Cells expressing NPM1-RARA were more resistant to apoptotic stimuli. This work identifies the TP53 tumor suppressor as a novel target through which NPM1-RARA impacts leukemogenesis, and confirms the importance of impairment of TP53 in establishment of the APL phenotype. PMID:26754533

  8. Ten-Year Comparison of Oxidized Zirconium and Cobalt-Chromium Femoral Components in Total Knee Arthroplasty

    Science.gov (United States)

    Roe, Justin; Vioreanu, Mihai; Salmon, Lucy; Waller, Alison; Pinczewski, Leo

    2016-01-01

    Objective: The purpose of this study was to determine if oxidized zirconium femoral components had better outcomes than cobalt-chromium in vivo at medium and long term and if the use of oxidized zirconium components had clinical adverse effects. Methods: Forty consecutive patients (eighty knees) underwent simultaneous bilateral cruciate-retaining total knee arthroplasty for primary osteoarthritis from January 2002 to December 2003. For each patient, the knees were randomized to receive the oxidized zirconium femoral component, with the contralateral knee receiving the cobalt-chromium component. Outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index, Knee Injury and Osteoarthritis Outcome Score, Knee Society score, and British Orthopaedic Association patient satisfaction scale. Radiographic outcomes include the Knee Society total knee arthroplasty roentgenographic evaluation and scoring system and measurement of radiographic wear. Patients and assessors were blinded to the treatment groups and results. Results: There were no significant differences in clinical, subjective, and radiographic outcomes between the two implants at ten years postoperatively. Ten years following surgery, 36% of the patients preferred the cobalt-chromium knee compared with 11% who preferred the oxidized zirconium knee (p = 0.02) and 53% had no preference. Conclusions: Ten-year outcomes after total knee arthroplasty with oxidized zirconium and cobalt-chromium femoral components showed no significant differences in clinical, subjective, and radiographic outcomes. Patients had no preference or preferred the cobalt chromium prosthesis to the oxidized zirconium prosthesis. There were no adverse effects associated with the use of oxidized zirconium femoral implants.

  9. Serum chromium levels in gestational diabetes mellitus

    Directory of Open Access Journals (Sweden)

    P G Sundararaman

    2012-01-01

    Full Text Available Objective: To measure serum chromium level in women with gestational diabetes mellitus (GDM from Chennai, South India. Materials and Methods: Thirty women with gestational diabetes, 60 age matched controls. Inclusion criteria: Gestational age 22-28 weeks, age group 20-35 years. Exclusion Criteria: Gestational age beyond 28 weeks, malnutrition or presence of infection. Serum chromium was measured using inductive couple plasma emission spectrometer. Results: Serum chromium levels of women with GDM, 1.59+/-0.02 ng/ml (range: 0.16-4.0 ng/ml were lower than in controls (4.58+/-0.62 ng/ml; range 0.82-5.33 ng/ml (P < 0.001. However, there were no significant differences among cases and controls when subdivided by parity. Conclusions: Women with GDM from a South Indian city had lower levels of serum chromium compared to pregnant women without GDM. Studies may be done whether chromium supplementation is useful in this group of women.

  10. Flashlamp-pumped lasing of chromium-doped GSG garnet

    International Nuclear Information System (INIS)

    The implications for the practical use of chromium:GSGG in lamp-pumped tunable lasers are discussed in this paper. The authors report here some major improvements in the performance of the flashlamp-pumped chromium:GSGG laser

  11. Chromium isotope uptake in carbonates

    DEFF Research Database (Denmark)

    Rodler, Alexandra

    composition of contemporaneous seawater. Marine carbonates are ubiquitous throughout Earth’s rock record rendering them a particularly interesting archive for constraining past changes in ocean chemistry. This thesis includes an investigation of the fractionation behavior of Cr isotopesduring coprecipitation.......The redox changes of past surface environments can be explored using the Cr isotope composition of ancient marine carbonates, where a marginal offset compared to contemporaneous seawater δ53Cr is expected and the degree of contamination and later diagenetic alteration can be evaluated. Improved...

  12. Cellular adaptation to hypoxia and p53 transcription regulation

    Institute of Scientific and Technical Information of China (English)

    Yang ZHAO; Xue-qun CHEN; Ji-zeng DU

    2009-01-01

    Tumor suppressor p53 is the most frequently mutated gene in human tumors. Meanwhile, under stress conditions, p53 also acts as a transcription factor, regulating the expression of a series of target genes to maintain the integrity of genome. The target genes of p53 can be classified into genes regulating cell cycle arrest, genes involved in apoptosis, and genes inhibiting angiogenesis. p53 protein contains a transactivation domain, a sequence-specific DNA binding domain, a tetramerization domain, a non-specific DNA binding domain that recognizes damaged DNA, and a later identified proline-rich domain. Under stress, p53 proteins accumulate and are activated through two mechanisms. One, involving ataxia telangiectasia-mutated protein (ATM), is that the interaction between p53 and its down-regulation factor murine double minute 2 (MDM2) decreases, leading to p53 phosphorylation on Ser15, as determined by the post-translational mechanism; the other holds that p53 increases and is activated through the binding of ribosomal protein L26 (RPL26) or nucleolin to p53 mRNA 5' untranslated region (UTR), regulating p53 translation. Under hypoxia, p53 decreases transactivation and increases transrepression. The mutations outside the DNA binding domain of p53 also contribute to tumor progress, so further studies on p53 should also be focused on this direction. The subterranean blind mole rat Spalax in Israel is a good model for hypoxia-adaptation. The p53 of Spalax mutated in residue 172 and residue 207 from arginine to lysine, conferring it the ability to survive hypoxic conditions. This model indicates that p53 acts as a master gene of diversity formation during evolution.

  13. Determination of chromium combined with DNA, RNA and proteins in chromium-rich brewer's yeast by NAA

    International Nuclear Information System (INIS)

    The content of chromium in the DNA, RNA and protein fractions separated from chromium-rich and normal brewer's yeast was determined by neutron activation analysis (NAA). Our results show that the extracted relative amounts and concentrations of DNA, RNA and proteins have no significant difference for two types of yeast, but the chromium content in DNA, RNA and proteins fractions extracted from the chromium-rich yeast are substantially higher than those from the normal. In addition, the concentration of chromium in DNA is much higher than that in RNA and proteins. It is evident that the inorganic chromium compounds can enter the yeast cell during the yeast cultivation in the chromium-containing culture medium and are converted into organic chromium species, which are combined with DNA, RNA and proteins. (author)

  14. Hexavalent and trivalent chromium in leather: What should be done?

    Science.gov (United States)

    Moretto, Angelo

    2015-11-01

    Trivalent chromium compounds are used for leather tanning, and chromium may be released during use of leather goods. In certain instances, small amounts of hexavalent chromium can be formed and released. Both trivalent and hexavalent chromium can elicit allergic skin reaction in chromium sensitised subjects, the latter being significantly more potent. Induction of sensitisation only occurs after exposure to hexavalent chromium. A minority of subjects are sensitised to chromium, and in a fraction of these subjects allergic skin reaction have been described after wearing leather shoes or, less frequently, other leather goods. The evidence that in all these cases the reaction is related to hexavalent chromium is not always strong. The content of hexavalent chromium in leather is regulated in European Union, but rate of release rather than content is relevant for allergic skin reaction. The role of trivalent chromium appear much less relevant if at all. Modern tanning procedure do not pose significant risk due to either hexavalent or trivalent chromium. Dismissing bad quality and worn-off leather goods is relevant in reducing or eliminating the skin reaction. It should also be pointed out that shoe components or substances other than chromium in leather may cause allergic/irritative skin reactions.

  15. Chromium allergy and dermatitis: prevalence and main findings

    DEFF Research Database (Denmark)

    Bregnbak, David; Johansen, Jeanne D.; Jellesen, Morten Stendahl;

    2015-01-01

    The history of chromium as an allergen goes back more than a century, and includesan interventional success with national legislation that led to significant changes inthe epidemiology of chromium allergy in construction workers. The 2015 EU Leather Regulation once again put a focus on chromium...

  16. Thermodynamic properties of chromium bearing slags and minerals. A review

    Energy Technology Data Exchange (ETDEWEB)

    Xiao Yanping; Holappa, L.

    1996-12-31

    In this report, the thermodynamic properties of chromium bearing slags and minerals were reviewed based on the available information in the literature. It includes the analysing methods for oxidation state of chromium in slags, oxidation state of chromium and activities of chromium oxides in slags and minerals. The phase diagrams of chromium oxide systems and chromium distributions between slag and metal phases are also covered ill this review. Concerning the analysing methods, it was found that most of the available approaches are limited to iron free slag systems and the sample preparation is very sensitive to the analysing results. In silicate slags under reducing atmosphere, divalent and trivalent chromium co-exist in the slags. It is agreed that the fraction of divalent chromium to total chromium increases with higher temperature, lower slag basicity and oxygen potential. For the slags under oxidising atmosphere, trivalent, pentavalent and hexavalent states were reported to be stable. The activities of CrO and CrO{sub 1.5} were concluded to have positive deviation from ideal solution. Slag basicity has a positive effect and temperature has a negative effect on the activities of chromium oxides. The phase diagrams of the Cr-O, binary, and ternary chromium containing oxide systems have been examined systematically. The analysis shows that the data on the quaternary and quinary systems are insufficient, and require further investigation. The most important features of the chromium containing silicate slags are the large miscibility gaps and the stability of the chromite spinel. (orig.) (76 refs.)

  17. 21 CFR 73.1015 - Chromium-cobalt-aluminum oxide.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Chromium-cobalt-aluminum oxide. 73.1015 Section 73... LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1015 Chromium-cobalt-aluminum oxide. (a) Identity. The color additive chromium-cobalt-aluminum oxide is a blue-green pigment obtained by calcining...

  18. Hexavalent and trivalent chromium in leather: What should be done?

    Science.gov (United States)

    Moretto, Angelo

    2015-11-01

    Trivalent chromium compounds are used for leather tanning, and chromium may be released during use of leather goods. In certain instances, small amounts of hexavalent chromium can be formed and released. Both trivalent and hexavalent chromium can elicit allergic skin reaction in chromium sensitised subjects, the latter being significantly more potent. Induction of sensitisation only occurs after exposure to hexavalent chromium. A minority of subjects are sensitised to chromium, and in a fraction of these subjects allergic skin reaction have been described after wearing leather shoes or, less frequently, other leather goods. The evidence that in all these cases the reaction is related to hexavalent chromium is not always strong. The content of hexavalent chromium in leather is regulated in European Union, but rate of release rather than content is relevant for allergic skin reaction. The role of trivalent chromium appear much less relevant if at all. Modern tanning procedure do not pose significant risk due to either hexavalent or trivalent chromium. Dismissing bad quality and worn-off leather goods is relevant in reducing or eliminating the skin reaction. It should also be pointed out that shoe components or substances other than chromium in leather may cause allergic/irritative skin reactions. PMID:26361854

  19. Collisional properties of trapped cold chromium atoms

    CERN Document Server

    Pavlovich, Z; Côté, R; Sadeghpour, H R; Pavlovic, Zoran; Roos, Bjoern O.; Côté, Robin

    2004-01-01

    We report on calculations of the elastic cross section and thermalization rate for collision between two maximally spin-polarized chromium atoms in the cold and ultracold regimes, relevant to buffer-gas and magneto-optical cooling of chromium atoms. We calculate ab initio potential energy curves for Cr2 and the van der Waals coefficient C6, and construct interaction potentials between two colliding Cr atoms. We explore the effect of shape resonances on elastic cross section, and find that they dramatically affect the thermalization rate. Our calculated value for the s-wave scattering length is compared in magnitude with a recent measurement at ultracold temperatures.

  20. Studying chromium biosorption using arabica coffee leaves

    Directory of Open Access Journals (Sweden)

    Luis Carlos Florez García

    2010-05-01

    Full Text Available This work was aimed at providing an alternative for removing heavy metals such as chromium from waste water (effluent from the leather industry and galvanoplasty (coating with a thin layer of metal by electrochemical means, using coffee leaves as bio- mass. Using arabica coffee (Castle variety leaves led to 82% chromium removal efficiency for 1,000 mg/L synthetic dissolutions in 4 pH dissolution operating conditions, 0 rpm agitation, 0.149 mm diameter biomass particle size and 0.85 g/ml biomass / dissolution volume ratio.

  1. Strategies for chromium bioremediation of tannery effluent.

    Science.gov (United States)

    Garg, Satyendra Kumar; Tripathi, Manikant; Srinath, Thiruneelakantan

    2012-01-01

    Bioremediation offers the possibility of using living organisms (bacteria, fungi, algae,or plants), but primarily microorganisms, to degrade or remove environmental contaminants, and transform them into nontoxic or less-toxic forms. The major advantages of bioremediation over conventional physicochemical and biological treatment methods include low cost, good efficiency, minimization of chemicals, reduced quantity of secondary sludge, regeneration of cell biomass, and the possibility of recover-ing pollutant metals. Leather industries, which extensively employ chromium compounds in the tanning process, discharge spent-chromium-laden effluent into nearby water bodies. Worldwide, chromium is known to be one of the most common inorganic contaminants of groundwater at pollutant hazardous sites. Hexavalent chromium poses a health risk to all forms of life. Bioremediation of chromium extant in tannery waste involves different strategies that include biosorption, bioaccumulation,bioreduction, and immobilization of biomaterial(s). Biosorption is a nondirected physiochemical interaction that occurs between metal species and the cellular components of biological species. It is metabolism-dependent when living biomass is employed, and metabolism-independent in dead cell biomass. Dead cell biomass is much more effective than living cell biomass at biosorping heavy metals, including chromium. Bioaccumulation is a metabolically active process in living organisms that works through adsorption, intracellular accumulation, and bioprecipitation mechanisms. In bioreduction processes, microorganisms alter the oxidation/reduction state of toxic metals through direct or indirect biological and chemical process(es).Bioreduction of Cr6+ to Cr3+ not only decreases the chromium toxicity to living organisms, but also helps precipitate chromium at a neutral pH for further physical removal,thus offering promise as a bioremediation strategy. However, biosorption, bioaccumulation, and

  2. Standard Specification for Nickel-Chromium-Molybdenum-Columbium Alloy (UNS N06625), Nickel-Chromium-Molybdenum-Silicon Alloy (UNS N06219), and Nickel-Chromium-Molybdenum-Tungsten Alloy (UNS N06650) Rod and Bar

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2014-01-01

    Standard Specification for Nickel-Chromium-Molybdenum-Columbium Alloy (UNS N06625), Nickel-Chromium-Molybdenum-Silicon Alloy (UNS N06219), and Nickel-Chromium-Molybdenum-Tungsten Alloy (UNS N06650) Rod and Bar

  3. Fluctuations in Precambrian atmospheric oxygenation recorded by chromium isotopes

    Science.gov (United States)

    Frei, Robert; Gaucher, Claudio; Poulton, Simon W.; Canfield, Don E.

    2009-09-01

    Geochemical data suggest that oxygenation of the Earth's atmosphere occurred in two broad steps. The first rise in atmospheric oxygen is thought to have occurred between ~2.45 and 2.2Gyr ago, leading to a significant increase in atmospheric oxygen concentrations and concomitant oxygenation of the shallow surface ocean. The second increase in atmospheric oxygen appears to have taken place in distinct stages during the late Neoproterozoic era (~800-542Myr ago), ultimately leading to oxygenation of the deep ocean ~580Myr ago, but details of the evolution of atmospheric oxygenation remain uncertain. Here we use chromium (Cr) stable isotopes from banded iron formations (BIFs) to track the presence of Cr(VI) in Precambrian oceans, providing a time-resolved picture of the oxygenation history of the Earth's atmosphere-hydrosphere system. The geochemical behaviour of Cr is highly sensitive to the redox state of the surface environment because oxidative weathering processes produce the oxidized hexavalent [Cr(VI)] form. Oxidation of reduced trivalent [Cr(III)] chromium on land is accompanied by an isotopic fractionation, leading to enrichment of the mobile hexavalent form in the heavier isotope. Our fractionated Cr isotope data indicate the accumulation of Cr(VI) in ocean surface waters ~2.8 to 2.6Gyr ago and a likely transient elevation in atmospheric and surface ocean oxygenation before the first great rise of oxygen 2.45-2.2Gyr ago (the Great Oxidation Event). In ~1.88-Gyr-old BIFs we find that Cr isotopes are not fractionated, indicating a decline in atmospheric oxygen. Our findings suggest that the Great Oxidation Event did not lead to a unidirectional stepwise increase in atmospheric oxygen. In the late Neoproterozoic, we observe strong positive fractionations in Cr isotopes (δ53Cr up to +4.9‰), providing independent support for increased surface oxygenation at that time, which may have stimulated rapid evolution of macroscopic multicellular life.

  4. The isotopic composition of authigenic chromium in anoxic marine sediments: A case study from the Cariaco Basin

    OpenAIRE

    Reinhard, Christopher T.; Planavsky, Noah J.; Wang, Xiangli; Fischer, Woodward W.; Johnson, Thomas M.; Lyons, Timothy W.

    2014-01-01

    Chromium (Cr) isotopes are an emerging proxy for tracking redox processes at the Earth's surface. However, there has been limited exploration of the Cr isotope record of modern and recent marine sediments. The basic inorganic chemistry of Cr suggests that anoxic marine basins should factor prominently in the global Cr cycle and that sediments deposited within anoxic basins may offer a valuable Cr isotope archive throughout Earth's history. Here, we present δ^(53)Cr data from sediments of the ...

  5. Small-Molecule Inhibitors of the MDM2-p53 Protein-Protein Interaction to Reactivate p53 Function: A Novel Approach for Cancer Therapy

    OpenAIRE

    Shangary, Sanjeev; Wang, Shaomeng

    2009-01-01

    Tumor suppressor p53 is an attractive cancer therapeutic target because it can be functionally activated to eradicate tumors. Direct gene alterations in p53 or interaction between p53 and MDM2 proteins are two alternative mechanisms for the inactivation of p53 function. Designing small molecules to block the MDM2-p53 interaction and reactivate the p53 function is a promising therapeutic strategy for the treatment of cancers retaining wild-type p53. This review will highlight recent advances i...

  6. EVI1 targets ΔNp63 and upregulates the cyclin dependent kinase inhibitor p21 independent of p53 to delay cell cycle progression and cell proliferation in colon cancer cells.

    Science.gov (United States)

    Nayak, Kasturi Bala; Kuila, Nivedita; Das Mohapatra, Alok; Panda, Aditya K; Chakraborty, Soumen

    2013-08-01

    Several lines of evidence suggest that specific transcriptional events are involved in cell cycle, proliferation and differentiation processes; however, their deregulation by proto-oncogenes are involved in the development of leukemia and tumors. One such proto-oncogene is ecotropic viral integration site I which can differentially effect cell cycle progression and proliferation, in cell types of different origin. Our data for the first time shows that ecotropic viral integration site I binds to ΔNp63 promoter element directly and down regulates its expression. Down regulation of ΔNp63 induces the expression of p21 in HT-29 cells and also in colon carcinoma cells that do not express p53 including patient samples expressing low level of p53, that eventually delay cell cycle progression at G0/G1 phase. Concomitant silencing of ecotropic viral integration site I from the cells or introduction of ΔNp63 to the cells significantly rescued this phenotype, indicating the growth defect induced by ΔNp63 deficiency to be, at least in part, attributable to ecotropic viral integration site I function. The mutual regulation between ecotropic viral integration site I and ΔNp63 may constitute a novel axis which might affect the downstream pathways in cells that do not express functional p53.

  7. The effect of chronic chromium exposure on the health of Chinook salmon (Oncorhynchus tshawytscha)

    Energy Technology Data Exchange (ETDEWEB)

    Farag, Aida M. [United States Geological Survey, Columbia Environmental Research Center, Jackson Field Research Station, P.O. Box 1089, Jackson, WY 83001 (United States)]. E-mail: aida_farag@usgs.gov; May, Thomas [United States Geological Survey, Columbia Environmental Research Center, Columbia, MO 65201 (United States); Marty, Gary D. [Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, 1 Shields Ave., Davis, CA 95616-8732 (United States); Easton, Michael [International EcoGen Inc., 2015 McLallen Court, North Vancouver, BC, Canada V7P 3H6 (Canada); Harper, David D. [United States Geological Survey, Columbia Environmental Research Center, Jackson Field Research Station, P.O. Box 1089, Jackson, WY 83001 (United States); Little, Edward E. [United States Geological Survey, Columbia Environmental Research Center, Columbia, MO 65201 (United States); Cleveland, Laverne [United States Geological Survey, Columbia Environmental Research Center, Columbia, MO 65201 (United States)

    2006-03-10

    This study was designed to determine fish health impairment of Chinook salmon (Oncorhynchus tshawytscha) exposed to chromium. Juvenile Chinook salmon were exposed to aqueous chromium concentrations (0-266 {mu}g l{sup -1}) that have been documented in porewater from bottom sediments and in well waters near salmon spawning areas in the Columbia River in the northwestern United States. After Chinook salmon parr were exposed to 24 and 54 {mu}g Cr l{sup -1} for 105 days, neither growth nor survival of parr was affected. On day 105, concentrations were increased from 24 to 120 {mu}g Cr l{sup -1} and from 54 to 266 {mu}g Cr l{sup -1} until the end of the experiment on day 134. Weight of parr was decreased in the 24/120 {mu}g Cr l{sup -1} treatment, and survival was decreased in the 54/266 {mu}g Cr l{sup -1} treatment. Fish health was significantly impaired in both the 24/120 and 54/266 {mu}g Cr l{sup -1} treatments. The kidney is the target organ during chromium exposures through the water column. The kidneys of fish exposed to the greatest concentrations of chromium had gross and microscopic lesions (e.g. necrosis of cells lining kidney tububules) and products of lipid peroxidation were elevated. These changes were associated with elevated concentrations of chromium in the kidney, and reduced growth and survival. Also, variations in DNA in the blood were associated with pathological changes in the kidney and spleen. These changes suggest that chromium accumulates and enters the lipid peroxidation pathway where fatty acid damage and DNA damage (expressed as chromosome changes) occur to cause cell death and tissue damage. While most of the physiological malfunctions occurred following parr exposures to concentrations {>=}120 {mu}g Cr l{sup -1}, nuclear DNA damage followed exposures to 24 {mu}g Cr l{sup -1}, which was the smallest concentration tested. The abnormalities measured during this study are particularly important because they are associated with impaired growth

  8. Electrodeposition of black chromium thin films from trivalent chromium-ionic liquid solution

    OpenAIRE

    Eugénio, S.; Vilar, Rui; C. M. Rangel; Baskaran, I.

    2009-01-01

    In the present study, black chromium thin films were electrodeposited from a solution of 1-butyl-3- methylimidazolium tetrafluoroborate ([BMIm][BF4] ionic liquid containing trivalent chromium (Cr(III)). Homogeneous and well adherent coatings have been obtained on nickel, copper and stainless steel substrates. The nucleation and growth of the films were investigated by cyclic voltammetry and current-density/time transient techniques. SEM/EDS, XPS and XRD were used to study the morphology, chem...

  9. Reduction of Hexavalent Chromium by Viable Cells of Chromium Resistant Bacteria Isolated from Chromite Mining Environment

    OpenAIRE

    Satarupa Dey; Baishali Pandit; A. K. Paul

    2014-01-01

    Environmental contamination of hexavalent chromium [Cr(VI)] is of serious concern for its toxicity as well as mutagenic and carcinogenic effects. Bacterial chromate reduction is a cost-effective technology for detoxification as well as removal of Cr(VI) from polluted environment. Chromium resistant and reducing bacteria, belonging to Arthrobacter, Pseudomonas, and Corynebacterium isolated from chromite mine overburden and seepage samples of Orissa, India, were found to tolerate 12–18 mM Cr(VI...

  10. Reduction of Chromium-VI by Chromium Resistant Lactobacilli: A Prospective Bacterium for Bioremediation

    OpenAIRE

    Mishra, Ritesh; Sinha, Vartika; Kannan, Ambrose; Upreti, Raj K.

    2012-01-01

    Chromium is a toxic heavy metal, which primarily exists in two inorganic forms, Cr (VI) and Cr (III). Highly soluble hexavalent chromium is carcinogenic due to its oxidizing nature. It is well established that the intestinal bacteria including Lactobacilli have regulatory effect on intestinal homeostasis and a breakdown in the relationship between intestinal cells and bacteria results in the manifestation of gastrointestinal (GI) disorders. In this study Cr (VI) resistance was developed in La...

  11. P53 family and cellular stress responses in cancer

    Directory of Open Access Journals (Sweden)

    Johanna ePflaum

    2014-10-01

    Full Text Available p53 is an important tumor suppressor gene, which is stimulated by cellular stress like ionizing radiation, hypoxia, carcinogens and oxidative stress. Upon activation p53 leads to cell cycle arrest and promotes DNA repair or induces apoptosis via several pathways. p63 and p73 are structural homologs of p53 that can act similarly to the protein but also hold functions distinct from p53. Today more than forty different isoforms of the p53 family members are known. They result from transcription via different promoters and alternative splicing. Some isoforms have carcinogenic properties and mediate resistance to chemotherapy. Therefore, expression patterns of the p53 family genes can offer prognostic information in several malignant tumors. Furthermore, the p53 family constitutes a potential target for cancer therapy. Small molecules (e.g. Nutlins, RITA, PRIMA-1, and MIRA-1 among others have been objects of intense research interest in recent years. They restore pro-apoptotic wild-type p53 function and were shown to break chemotherapeutic resistance. Due to p53 family interactions small molecules also influence p63 and p73 activity. Thus, the members of the p53 family are key players in the cellular stress response in cancer and are expected to grow in importance as therapeutic targets.

  12. The electronic structure of antiferromagnetic chromium

    DEFF Research Database (Denmark)

    Skriver, Hans Lomholt

    1981-01-01

    The author has used the local spin density formalism to perform self-consistent calculations of the electronic structure of chromium in the non-magnetic and commensurate antiferromagnetic phases, as a function of the lattice parameter. A change of a few per cent in the atomic radius brings...

  13. Flashlamp-pumped lasing of chromium: GSGG

    International Nuclear Information System (INIS)

    Lasing action in chromium-doped gadolinium scandium gallium garnet (Cr:GSGG) is well established for both CW/sup (1)/ and flashlamp/sup (2)/ pumping. This paper describes an investigation of flashlamp-pumped Cr:GSGG lasers and indicates some of the factors which limit performance

  14. Defect structure of electrodeposited chromium layers

    CERN Document Server

    Marek, T; Vertes, A; El-Sharif, M; McDougall, J; Chisolm, C U

    2000-01-01

    Positron annihilation spectroscopy was applied to study the effects of pre-treatment and composition of substrates on the quality and defect structure of electrodeposited thick chromium coatings. The results show that both parameters are important, and a scenario is proposed why the mechanically polished substrate gives more defective film than the electro polished one.

  15. 29 CFR 1910.1026 - Chromium (VI).

    Science.gov (United States)

    2010-07-01

    ... Enhancements In Lieu of LEV Retrofitting • Eductors. Many chemical baths are currently mixed via air agitation... requirements of the Hazard Communication Standard, 29 CFR 1910.1200. (3) Cleaning and replacement. (i) The... CFR 1910.141. Where skin contact with chromium (VI) occurs, the employer shall provide...

  16. Biological groundwater treatment for chromium removal at low hexavalent chromium concentrations.

    Science.gov (United States)

    Mamais, Daniel; Noutsopoulos, Constantinos; Kavallari, Ioanna; Nyktari, Eleni; Kaldis, Apostolos; Panousi, Eleni; Nikitopoulos, George; Antoniou, Kornilia; Nasioka, Maria

    2016-06-01

    The objective of this work is to develop and evaluate biological groundwater treatment systems that will achieve hexavalent chromium reduction and total chromium removal from groundwater at hexavalent chromium (Cr(VI)) groundwater concentrations in the 0-200 μg/L range. Three lab-scale units operated, as sequencing batch reactors (SBR) under aerobic, anaerobic and anaerobic-aerobic conditions. All systems received groundwater with a Cr(VI) content of 200 μg/L. In order to support biological growth, groundwater was supplemented with milk, liquid cheese whey or a mixture of sugar and milk to achieve a COD concentration of 200 mg/L. The results demonstrate that a fully anaerobic system or an anaerobic-aerobic system dosed with simple or complex external organic carbon sources can lead to practically complete Cr(VI) reduction to Cr(III). The temperature dependency of maximum Cr(VI) removal rates can be described by the Arrhenius relationship. Total chromium removal in the biological treatment systems was not complete because a significant portion of Cr(III) remained in solution. An integrated system comprising of an anaerobic SBR followed by a sand filter achieved more than 95% total chromium removal thus resulting in average effluent total and dissolved chromium concentrations of 7 μg/L and 3 μg/L, respectively. PMID:26971177

  17. Chromium(III) and chromium(VI) surface treated galvanized steel for outdoor constructions: environmental aspects.

    Science.gov (United States)

    Lindström, David; Hedberg, Yolanda; Odnevall Wallinder, Inger

    2010-06-01

    The long-term degradation of chromium(III) (Zn-Cr(III)) and chromium(VI)-based (Zn-Cr(VI)) surface treatments on galvanized steel and their capacities to hinder the release of zinc induced by atmospheric corrosion at nonsheltered urban and marine exposure conditions for 2 years are investigated. Compared to bare zinc sheet, both surface treatments revealed high corrosion protection abilities and capacities to hinder the release of zinc, still evident after 2 years of exposure. The zinc barrier properties of the thinner Zn-Cr(VI) (10 nm) treatment were during the first 100 days of urban exposure slightly improved compared with Zn-Cr(III) (35 nm). However, their long-term protection capacities were inverse. Released concentrations of total chromium correspond to annual release rates less than 0.000032 (Zn-Cr(III)) and 0.00014 g Cr m(-2) yr(-1) (Zn-Cr(VI)) after 1 year of urban exposure. Aging by indoor storage of the surface treatments prior to outdoor exposure reduced the released Cr concentrations from the surface treatments. No Cr(VI) was released from the aged surfaces but from the freshly exposed Zn-Cr(VI). Marine exposure conditions resulted in a faster reduction of chromate to chromium(III)oxide compared with urban conditions, and a significantly lower amount of both chromium(III) and chromium(VI) released from Zn-Cr(VI) at the marine site compared with the urban site. PMID:20462267

  18. Abrasion Resistance of as-Cast High-Chromium Cast Iron

    Directory of Open Access Journals (Sweden)

    Pokusová Marcela

    2014-12-01

    Full Text Available High chromium cast irons are widely used as abrasion resistant materials. Their properties and wear resistance depend on carbides and on the nature of the matrix supporting these carbides. The paper presents test results of irons which contain (in wt.% 18-22 Cr and 2-5 C, and is alloyed by 1.7 Mo + 5 Ni + 2 Mn to improve the toughness. Tests showed as-cast irons with mostly austenitic matrix achieved hardness 36-53 HRC but their relative abrasion-resistance was higher than the tool steel STN 19436 heat treated on hardness 60 HRC.

  19. A Kinetic Model of Chromium in a Flame

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Chromium has been identified as a carcinogenic metal.Incineration is the useful method for disposal of toxic chromium hazard waste and a chromium kinetic model in a flame is very important to study chromium oxidation.Chromium chemical kinetics over a range of temperatures of a hydrogen/air flame is proposed.Nine chromium compounds and fifty-eight reversible chemical reactions were considered The forward reaction rates are calculated based on the molecular collision approach for unknown ones and Arrhenius's Law for known ones.The backward reaction rates were calculated according to forward reaction rates, the equilibrium constants and chemical thermodynamics.It is verified by several equilibrium cases and is tested by a hydrogen/air diffusion flame.The results show that the kinetic model could be used in cases in which the chromium kinetics play an important role in a flame

  20. P53 family members modulate the expression of PRODH, but not PRODH2, via intronic p53 response elements.

    Directory of Open Access Journals (Sweden)

    Ivan Raimondi

    Full Text Available The tumor suppressor p53 was previously shown to markedly up-regulate the expression of the PRODH gene, encoding the proline dehydrogenase (PRODH enzyme, which catalyzes the first step in proline degradation. Also PRODH2, which degrades 4-hydroxy-L-proline, a product of protein (e.g. collagen catabolism, was recently described as a p53 target. Here, we confirmed p53-dependent induction of endogenous PRODH in response to genotoxic damage in cell lines of different histological origin. We established that over-expression of TAp73β or TAp63β is sufficient to induce PRODH expression in p53-null cells and that PRODH expression parallels the modulation of endogenous p73 by genotoxic drugs in several cell lines. The p53, p63, and p73-dependent transcriptional activation was linked to specific intronic response elements (REs, among those predicted by bioinformatics tools and experimentally validated by a yeast-based transactivation assay. p53 occupancy measurements were validated in HCT116 and MCF7 human cell lines. Conversely, PRODH2 was not responsive to p63 nor p73 and, at best, could be considered a weak p53 target. In fact, minimal levels of PRODH2 transcript induction by genotoxic stress was observed exclusively in one of four p53 wild-type cell lines tested. Consistently, all predicted p53 REs in PRODH2 were poor matches to the p53 RE consensus and showed very weak responsiveness, only to p53, in the functional assay. Taken together, our results highlight that PRODH, but not PRODH2, expression is under the control of p53 family members, specifically p53 and p73. This supports a deeper link between proteins of the p53-family and metabolic pathways, as PRODH modulates the balance of proline and glutamate levels and those of their derivative alpha-keto-glutarate (α-KG under normal and pathological (tumor conditions.

  1. Designing cobalt chromium removable partial dentures for patients with shortened dental arches: a pilot survey.

    Science.gov (United States)

    Nassani, M Z; Devlin, H; Tarakji, B; McCord, J F

    2011-08-01

    The aim of this survey was to investigate the quality of prescription for the fabrication of cobalt chromium removable partial dentures (RPDs) that are used to extend the shortened dental arches (SDAs). A survey of four commercial dental laboratories located in northern England was conducted. The target of this survey was cobalt chromium RPDs that were requested to restore SDAs comprising the anterior teeth and 2-4 premolars. Dentists' prescriptions were scrutinised, and a special data collection form was completed accordingly. A total of 94 dentists' prescriptions and associated SDA casts were examined. Almost all the requested cobalt chromium RPDs were clasp-retained RPDs (97%). Scrutinising the 91 prescriptions for clasp-retained cobalt chromium RPDs showed that dentists' prescriptions did not have any instructions about the design of the partial denture in a considerable proportion of the cases (32%). Teeth to be clasped were identified clearly in 45% of the prescriptions. A majority of the dentists (64%) failed to provide any instructions about the design of the rests to be placed on the most posterior premolar abutment teeth. A considerable proportion of the dentists delegated the task of selecting the type of the major connector to the dental technician (41%). Only 21 (23%) of the examined casts had clearly defined rest seat preparation. The outcome of this pilot survey shows inadequate quality of prescription in designing RPDs for patients with SDAs. This finding has an ethical and clinical bearing and does not fit with current legal guidelines relevant to designing RPDs. PMID:21175736

  2. Expression of TP53 isoforms p53β or p53γ enhances chemosensitivity in TP53(null cell lines.

    Directory of Open Access Journals (Sweden)

    Elisabeth Silden

    Full Text Available The carboxy-terminal truncated p53 alternative spliced isoforms, p53β and p53γ, are expressed at disparate levels in cancer and are suggested to influence treatment response and therapy outcome. However, their functional role in cancer remains to be elucidated. We investigated their individual functionality in the p53(null background of cell lines H1299 and SAOS-2 by stable retroviral transduction or transient transfection. Expression status of p53β and p53γ protein was found to correlate with increased response to camptothecin and doxorubicin chemotherapy. Decreased DNA synthesis and clonogenicity in p53β and p53γ congenic H1299 was accompanied by increased p21((CIP1/WAF1, Bax and Mdm2 proteins. Chemotherapy induced p53 isoform degradation, most prominent for p53γ. The proteasome inhibitor bortezomib substantially increased basal p53γ protein level, while the level of p53β protein was unaffected. Treatment with dicoumarol, a putative blocker of the proteasome-related NAD(PH quinone oxidoreductase NQO1, effectively attenuated basal p53γ protein level in spite of bortezomib treatment. Although in vitro proliferation and clonogenicity assays indicated a weak suppressive effect by p53β and p53γ expression, studies of in vivo subcutaneous H1299 tumor growth demonstrated a significantly increased growth by expression of either p53 isoforms. This study suggests that p53β and p53γ share functionality in chemosensitizing and tumor growth enhancement but comprise distinct regulation at the protein level.

  3. Expression of TP53 isoforms p53β or p53γ enhances chemosensitivity in TP53(null) cell lines.

    Science.gov (United States)

    Silden, Elisabeth; Hjelle, Sigrun M; Wergeland, Line; Sulen, André; Andresen, Vibeke; Bourdon, Jean-Christophe; Micklem, David R; McCormack, Emmet; Gjertsen, Bjørn Tore

    2013-01-01

    The carboxy-terminal truncated p53 alternative spliced isoforms, p53β and p53γ, are expressed at disparate levels in cancer and are suggested to influence treatment response and therapy outcome. However, their functional role in cancer remains to be elucidated. We investigated their individual functionality in the p53(null) background of cell lines H1299 and SAOS-2 by stable retroviral transduction or transient transfection. Expression status of p53β and p53γ protein was found to correlate with increased response to camptothecin and doxorubicin chemotherapy. Decreased DNA synthesis and clonogenicity in p53β and p53γ congenic H1299 was accompanied by increased p21((CIP1/WAF1)), Bax and Mdm2 proteins. Chemotherapy induced p53 isoform degradation, most prominent for p53γ. The proteasome inhibitor bortezomib substantially increased basal p53γ protein level, while the level of p53β protein was unaffected. Treatment with dicoumarol, a putative blocker of the proteasome-related NAD(P)H quinone oxidoreductase NQO1, effectively attenuated basal p53γ protein level in spite of bortezomib treatment. Although in vitro proliferation and clonogenicity assays indicated a weak suppressive effect by p53β and p53γ expression, studies of in vivo subcutaneous H1299 tumor growth demonstrated a significantly increased growth by expression of either p53 isoforms. This study suggests that p53β and p53γ share functionality in chemosensitizing and tumor growth enhancement but comprise distinct regulation at the protein level. PMID:23409163

  4. Xenogeneic human p53 DNA vaccination by electroporation breaks immune tolerance to control murine tumors expressing mouse p53.

    Directory of Open Access Journals (Sweden)

    Ruey-Shyang Soong

    Full Text Available The pivotal role of p53 as a tumor suppressor protein is illustrated by the fact that this protein is found mutated in more than 50% of human cancers. In most cases, mutations in p53 greatly increase the otherwise short half-life of this protein in normal tissue and cause it to accumulate in the cytoplasm of tumors. The overexpression of mutated p53 in tumor cells makes p53 a potentially desirable target for the development of cancer immunotherapy. However, p53 protein represents an endogenous tumor-associated antigen (TAA. Immunization against a self-antigen is challenging because an antigen-specific immune response likely generates only low affinity antigen-specific CD8(+ T-cells. This represents a bottleneck of tumor immunotherapy when targeting endogenous TAAs expressed by tumors. The objective of the current study is to develop a safe cancer immunotherapy using a naked DNA vaccine. The vaccine employs a xenogeneic p53 gene to break immune tolerance resulting in a potent therapeutic antitumor effect against tumors expressing mutated p53. Our study assessed the therapeutic antitumor effect after immunization with DNA encoding human p53 (hp53 or mouse p53 (mp53. Mice immunized with xenogeneic full length hp53 DNA plasmid intramuscularly followed by electroporation were protected against challenge with murine colon cancer MC38 while those immunized with mp53 DNA were not. In a therapeutic model, established MC38 tumors were also well controlled by treatment with hp53 DNA therapy in tumor bearing mice compared to mp53 DNA. Mice vaccinated with hp53 DNA plasmid also exhibited an increase in mp53-specific CD8(+ T-cell precursors compared to vaccination with mp53 DNA. Antibody depletion experiments also demonstrated that CD8(+ T-cells play crucial roles in the antitumor effects. This study showed intramuscular vaccination with xenogeneic p53 DNA vaccine followed by electroporation is capable of inducing potent antitumor effects against tumors

  5. OTUD5 regulates p53 stability by deubiquitinating p53.

    Directory of Open Access Journals (Sweden)

    Judong Luo

    Full Text Available BACKGROUND: The p53 tumour suppressor protein is a transcription factor that prevents oncogenic progression by activating the expression of apoptosis and cell-cycle arrest genes in stressed cells. The stability of p53 is tightly regulated by ubiquitin-dependent degradation, driven mainly by its negative regulators ubiquitin ligase MDM2. PRINCIPAL FINDINGS: In this study, we have identified OTUD5 as a DUB that interacts with and deubiquitinates p53. OTUD5 forms a direct complex with p53 and controls level of ubiquitination. The function of OTUD5 is required to allow the rapid activation of p53-dependent transcription and a p53-dependent apoptosis in response to DNA damage stress. CONCLUSIONS: As a novel deubiquitinating enzyme for p53, OTUD5 is required for the stabilization and the activation of a p53 response.

  6. Expression of TP53 Isoforms p53β or p53γ Enhances Chemosensitivity in TP53null Cell Lines

    OpenAIRE

    Elisabeth Silden; Hjelle, Sigrun M; Line Wergeland; André Sulen; Vibeke Andresen; Jean-Christophe Bourdon; Micklem, David R; Emmet McCormack; Bjørn Tore Gjertsen

    2013-01-01

    The carboxy-terminal truncated p53 alternative spliced isoforms, p53β and p53γ, are expressed at disparate levels in cancer and are suggested to influence treatment response and therapy outcome. However, their functional role in cancer remains to be elucidated. We investigated their individual functionality in the p53(null) background of cell lines H1299 and SAOS-2 by stable retroviral transduction or transient transfection. Expression status of p53β and p53γ protein was found to correlate wi...

  7. Expression of TP53 Isoforms p53β or p53γ Enhances Chemosensitivity in TP53null Cell Lines

    OpenAIRE

    Silden, Elisabeth; Hjelle, Sigrun M; Wergeland, Line; Sulen, André; Andresen, Vibeke; Bourdon, Jean-Christophe; Micklem, David R.; McCormack, Emmet; Gjertsen, Bjørn Tore

    2013-01-01

    The carboxy-terminal truncated p53 alternative spliced isoforms, p53β and p53γ, are expressed at disparate levels in cancer and are suggested to influence treatment response and therapy outcome. However, their functional role in cancer remains to be elucidated. We investigated their individual functionality in the p53null background of cell lines H1299 and SAOS-2 by stable retroviral transduction or transient transfection. Expression status of p53β and p53γ protein was found to correlate with...

  8. Tumor suppressor p53 meets microRNAs

    Institute of Scientific and Technical Information of China (English)

    Zhaohui Feng; Cen Zhang; Rui Wu; Wenwei Hu

    2011-01-01

    Tumor suppressor p53 plays a central role in tumor prevention. As a transcription factor, p53 mainly exerts its function through transcription regulation of its target genes to initiate various cellular responses. To maintain its proper function, p53 is tightly regulated by a wide variety of regulators in cells. Thus, p53, its regulators and regulated genes form a complex p53 network which is composed of hundreds of genes and their products. microRNAs (miRNAs) are a class of endogenously expressed, small non-coding RNA molecules which play a key role in regulation of gene expression at the post-transcriptional level. Recent studies have demonstrated that miRNAs interact with p53 and its network at multiple levels. p53 regulates the transcription expression and the maturation of a group of miRNAs. On the other hand, miRNAs can regulate the activity and function of p53 through direct repression of p53 or its regulators in cells. These findings have demonstrated that miRNAs are important components in the p53 network, and also added another layer of complexity to the p53 network.

  9. CHROMIUM INDUCED CYTOTOXICITY IN BLACKGRAM (VIGNA MUNGO L.

    Directory of Open Access Journals (Sweden)

    A. Chidambaram ، P. Sundaramoorthy ، A. Murugan ، K. Sankar Ganesh ، L. Baskaran

    2009-01-01

    Full Text Available Chromium is known to be highly toxic to biological systems. This study was designed to determine the mutagenic effects of different concentrations (0, 10, 25, 50, 100 and 200 mg/L of hexavalent chromium on root tip cells of blackgram (Vigna mungo L. Hepper. The blackgram seeds were equi-spacially arranged in sterilized petriplates lined with filter paper and they were treated with different concentrations of chromium solution. In germination studies, the morphological growth parameters such as germination percentage, root length, shoot length fresh weight and dry weight of blackgram seedlings were decreased with increasing dose of chromium concentrations. No germination of blackgram seeds was recorded at 300mg/l chromium concentration. Chromosome aberration assay was used to determine the mitotic indices and rate of chromosome aberration in blackgram root tip cells due to chromium treatment. The results showed that the mitotic indices were complicated due to different concentrations of chromium. However, the increase in chromium concentration has led to a gradual increase in the percentage of chromosomal aberration and mitotic index. The chromosome length, absolute chromosome length and average chromosome lengths were gradually found to decrease. There was no considerable change in 2n number of chromosome with the increase in chromium concentrations. It is concluded that the hexavalent chromium has significant mutagenic effect on the root tip cells of blackgram.

  10. Chromium supplementation improved post-stroke brain infarction and hyperglycemia.

    Science.gov (United States)

    Chen, Wen-Ying; Mao, Frank Chiahung; Liu, Chia-Hsin; Kuan, Yu-Hsiang; Lai, Nai-Wei; Wu, Chih-Cheng; Chen, Chun-Jung

    2016-04-01

    Hyperglycemia is common after acute stroke and is associated with a worse outcome of stroke. Thus, a better understanding of stress hyperglycemia is helpful to the prevention and therapeutic treatment of stroke. Chromium is an essential nutrient required for optimal insulin activity and normal carbohydrate and lipid metabolism. Beyond its nutritional effects, dietary supplement of chromium causes beneficial outcomes against several diseases, in particular diabetes-associated complications. In this study, we investigated whether post-stroke hyperglycemia involved chromium dynamic mobilization in a rat model of permanent focal cerebral ischemia and whether dietary supplement of chromium improved post-stroke injury and alterations. Stroke rats developed brain infarction, hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance. Post-stroke hyperglycemia was accompanied by elevated secretion of counter-regulatory hormones including glucagon, corticosterone, and norepinephrine, decreased insulin signaling in skeletal muscles, and increased hepatic gluconeogenesis. Correlation studies revealed that counter-regulatory hormone secretion showed a positive correlation with chromium loss and blood glucose increased together with chromium loss. Daily chromium supplementation increased tissue chromium levels, attenuated brain infarction, improved hyperglycemia, and decreased plasma levels of glucagon and corticosterone in stroke rats. Our findings suggest that stroke rats show disturbance of tissue chromium homeostasis with a net loss through urinary excretion and chromium mobilization and loss might be an alternative mechanism responsible for post-stroke hyperglycemia. PMID:26477944

  11. Comparative assessment of the apoptotic potential of silver nanoparticles synthesized by Bacillus tequilensis and Calocybe indica in MDA-MB-231 human breast cancer cells: targeting p53 for anticancer therapy

    Directory of Open Access Journals (Sweden)

    Gurunathan S

    2015-06-01

    Full Text Available Sangiliyandi Gurunathan, Jung Hyun Park, Jae Woong Han, Jin-Hoi KimDepartment of Animal Biotechnology, Konkuk University, Seoul, Republic of KoreaBackground: Recently, the use of nanotechnology has been expanding very rapidly in diverse areas of research, such as consumer products, energy, materials, and medicine. This is especially true in the area of nanomedicine, due to physicochemical properties, such as mechanical, chemical, magnetic, optical, and electrical properties, compared with bulk materials. The first goal of this study was to produce silver nanoparticles (AgNPs using two different biological resources as reducing agents, Bacillus tequilensis and Calocybe indica. The second goal was to investigate the apoptotic potential of the as-prepared AgNPs in breast cancer cells. The final goal was to investigate the role of p53 in the cellular response elicited by AgNPs.Methods: The synthesis and characterization of AgNPs were assessed by various analytical techniques, including ultraviolet-visible (UV-vis spectroscopy, X-ray diffraction (XRD, Fourier transform infrared (FTIR spectroscopy, dynamic light scattering (DLS, and transmission electron microscopy (TEM. The apoptotic efficiency of AgNPs was confirmed using a series of assays, including cell viability, leakage of lactate dehydrogenase (LDH, production of reactive oxygen species (ROS, DNA fragmentation, mitochondrial membrane potential, and Western blot.Results: The absorption spectrum of the yellow AgNPs showed the presence of nanoparticles. XRD and FTIR spectroscopy results confirmed the crystal structure and biomolecules involved in the synthesis of AgNPs. The AgNPs derived from bacteria and fungi showed distinguishable shapes, with an average size of 20 nm. Cell viability assays suggested a dose-dependent toxic effect of AgNPs, which was confirmed by leakage of LDH, activation of ROS, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL-positive cells in MDA

  12. Improvement on simultaneous determination of chromium species in aqueous solution by ion chromatography and chemiluminescence detection

    DEFF Research Database (Denmark)

    Gammelgaard, Bente; Liao, Y.P.; Jons, O.

    1997-01-01

    A sensitive method for the simultaneous determination of chromium(III) and chromium(VI) was chromatography and chemiluminescence detection. Two Dionex ion-exchange guard columns in series, CG5 and AG7, were used to separate chromium(III) from chromium(VI). Chromium(VI) was reduced by potassium su...

  13. A novel synthetic C-1 analogue of 7-deoxypancratistatin induces apoptosis in p53 positive and negative human colorectal cancer cells by targeting the mitochondria: enhancement of activity by tamoxifen.

    Science.gov (United States)

    Ma, Dennis; Tremblay, Phillip; Mahngar, Kevinjeet; Akbari-Asl, Pardis; Collins, Jonathan; Hudlicky, Tomas; McNulty, James; Pandey, Siyaram

    2012-06-01

    The natural compound pancratistatin (PST), isolated from the Hymenocallis littoralis plant, specifically induces apoptosis in many cancer cell lines. Unlike many other chemotherapeutics, PST is not genotoxic and has minimal adverse effects on non-cancerous cells. However, its availability for preclinical and clinical work is limited due to its low availability in its natural source and difficulties in its chemical synthesis. Several synthetic analogues of 7-deoxypancratistatin with different modifications at C-1 were synthesized and screened for apoptosis inducing activity in human colorectal cancer (CRC) cells. We found that a C-1 acetoxymethyl derivative of 7-deoxypancratistatin, JC-TH-acetate-4 (JCTH-4), was effective in inducing apoptosis in both p53 positive (HCT 116) and p53 negative (HT-29) human CRC cell lines, demonstrating similar efficacy to that of natural PST. JCTH-4 was able to decrease mitochondrial membrane potential (MMP), increase levels of reactive oxygen species in isolated mitochondria, cause release of the apoptogenic factor cytochrome c (Cyto c) from isolated mitochondria, and induce autophagy in HCT 116 and HT-29 cells. Interestingly, when JCTH-4 was administered with tamoxifen (TAM), there was an enhanced effect in apoptosis induction, reactive oxygen species (ROS) production and Cyto c release by isolated mitochondria, and autophagic induction by CRC cells. Minimal toxicity was exhibited by a normal human fetal fibroblast (NFF) and a normal colon fibroblast (CCD-18Co) cell line. Hence, JCTH-4 is a novel compound capable of selectively inducing apoptosis and autophagy in CRC cells alone and in combination with TAM and may serve as a safer and more effective alternative to current cancer therapies. PMID:21494837

  14. High chromium martensitic stainless linepipes

    Energy Technology Data Exchange (ETDEWEB)

    Asahi, H.; Muraki, T.; Inoue, H.; Tamehiro, H. [Nippon Steel Corp., Futtsu, Chiba (Japan). Steel Research Labs.

    1996-12-01

    Effects of chemical compositions on major properties of high Cr martensitic stainless steels with low C content for linepipe were investigated. Cr to CO{sub 2}-corrosion, Ni and N to low temperature toughness in HAZ and Mo to SSC resistances were clarified to be major governing factors. Three steels with different targeted performs which were developed based on the fundamental study results were easily arc-welded without pre-heating and showed good performance for both the base metal and heat affected zone of the weld. Galvanic corrosion in welded portion and hydrogen embrittlement under cathodic protection condition were also found not to be a serious problem.

  15. Production of basic chromium sulfate by using recovered chromium from ashes of thermally treated leather.

    Science.gov (United States)

    Dettmer, Aline; Nunes, Keila Guerra Pacheco; Gutterres, Mariliz; Marcílio, Nilson Romeu

    2010-04-15

    Leather wastes tanned with chromium are generated during the production process of leather, hence the wastes from hand crafted goods and footwear industries are a serious environmental problem. The thermal treatment of leather wastes can be one of the treatment options because the wastes are rich in chromium and can be used as a raw material for sodium chromate production and further to obtain several chromium compounds. The objective of this study was to utilize the chromium from leather wastes via basic chromium sulfate production to be subsequently applied in a hide tanning. The obtained results have shown that this is the first successful attempt to achieve desired base properties of the product. The result was achieved when the following conditions were applied: a molar ratio between sodium sulfite and sodium dichromate equal to 6; reaction time equal to 5 min before addition of sulfuric acid; pH of sodium dichromate solution equal to 2. Summarizing, there is an opportunity to utilize the dangerous wastes and reused them in the production scheme by minimizing or annulling the environmental impact and to attend a sustainable process development concept.

  16. Production of basic chromium sulfate by using recovered chromium from ashes of thermally treated leather.

    Science.gov (United States)

    Dettmer, Aline; Nunes, Keila Guerra Pacheco; Gutterres, Mariliz; Marcílio, Nilson Romeu

    2010-04-15

    Leather wastes tanned with chromium are generated during the production process of leather, hence the wastes from hand crafted goods and footwear industries are a serious environmental problem. The thermal treatment of leather wastes can be one of the treatment options because the wastes are rich in chromium and can be used as a raw material for sodium chromate production and further to obtain several chromium compounds. The objective of this study was to utilize the chromium from leather wastes via basic chromium sulfate production to be subsequently applied in a hide tanning. The obtained results have shown that this is the first successful attempt to achieve desired base properties of the product. The result was achieved when the following conditions were applied: a molar ratio between sodium sulfite and sodium dichromate equal to 6; reaction time equal to 5 min before addition of sulfuric acid; pH of sodium dichromate solution equal to 2. Summarizing, there is an opportunity to utilize the dangerous wastes and reused them in the production scheme by minimizing or annulling the environmental impact and to attend a sustainable process development concept. PMID:20031309

  17. Femtosecond laser surface structuring and oxidation of chromium thin coatings: Black chromium

    International Nuclear Information System (INIS)

    Highlights: • Oxidation of the chromium thin film to chromium oxide by femtosecond laser with a fundamental wavelength of 1064 nm. • Solar absorber from chromium oxide that low percentage reflectance. • Femtosecond laser oxidation, with a de-focused laser. • Chromium oxide formation by femtosecond laser in normal ambient. - Abstract: In view of their potential applications as selective solar absorbers, chromium coatings on float glass substrates were nano/micro structured by femtosecond laser in air. Raman and X-rays diffraction investigations confirmed the formation of an ultra-porous α-Cr2O3 layer at the surface; higher is the input laser power, enhanced is the crystallinity of the α-Cr2O3 layer. The α-Cr2O3 layer with the Cr underneath it in addition to the photo-induced porosity acted as a classical ceramic–metal nano-composite making the reflectance to decrease significantly within the spectral range of 190–1100 nm. The average reflectance decreased from 70 to 2%

  18. Femtosecond laser surface structuring and oxidation of chromium thin coatings: Black chromium

    Energy Technology Data Exchange (ETDEWEB)

    Kotsedi, L., E-mail: Kotsedi@tlabs.ac.za [UNESCO-UNISA Africa Chair in Nanosciences-Nanotechnology, College of Graduate Studies, University of South Africa, Muckleneuk Ridge, P.O. Box 392, Pretoria (South Africa); Nanosciences African Network (NANOAFNET), iThemba LABS-National Research Foundation, 1 Old Faure Road, Somerset West 7129, P.O. Box 722, Somerset West, Western Cape (South Africa); Nuru, Z.Y. [UNESCO-UNISA Africa Chair in Nanosciences-Nanotechnology, College of Graduate Studies, University of South Africa, Muckleneuk Ridge, P.O. Box 392, Pretoria (South Africa); Nanosciences African Network (NANOAFNET), iThemba LABS-National Research Foundation, 1 Old Faure Road, Somerset West 7129, P.O. Box 722, Somerset West, Western Cape (South Africa); Mthunzi, P. [National Laser Centre, Council for Scientific and Industrial Research, 0001 Pretoria (South Africa); Muller, T.F.G. [University of the Western Cape, Physics Department, Bellville, 7535 Cape Town (South Africa); Eaton, S.M. [Physics Department, Politecnico di Milano, Piazza Leonardo Da Vinci, 32, 20133 Milano (Italy); Julies, B. [University of the Western Cape, Physics Department, Bellville, 7535 Cape Town (South Africa); Manikandan, E. [UNESCO-UNISA Africa Chair in Nanosciences-Nanotechnology, College of Graduate Studies, University of South Africa, Muckleneuk Ridge, P.O. Box 392, Pretoria (South Africa); Nanosciences African Network (NANOAFNET), iThemba LABS-National Research Foundation, 1 Old Faure Road, Somerset West 7129, P.O. Box 722, Somerset West, Western Cape (South Africa); Ramponi, R. [Physics Department, Politecnico di Milano, Piazza Leonardo Da Vinci, 32, 20133 Milano (Italy); Maaza, M. [UNESCO-UNISA Africa Chair in Nanosciences-Nanotechnology, College of Graduate Studies, University of South Africa, Muckleneuk Ridge, P.O. Box 392, Pretoria (South Africa); Nanosciences African Network (NANOAFNET), iThemba LABS-National Research Foundation, 1 Old Faure Road, Somerset West 7129, P.O. Box 722, Somerset West, Western Cape (South Africa)

    2014-12-01

    Highlights: • Oxidation of the chromium thin film to chromium oxide by femtosecond laser with a fundamental wavelength of 1064 nm. • Solar absorber from chromium oxide that low percentage reflectance. • Femtosecond laser oxidation, with a de-focused laser. • Chromium oxide formation by femtosecond laser in normal ambient. - Abstract: In view of their potential applications as selective solar absorbers, chromium coatings on float glass substrates were nano/micro structured by femtosecond laser in air. Raman and X-rays diffraction investigations confirmed the formation of an ultra-porous α-Cr{sub 2}O{sub 3} layer at the surface; higher is the input laser power, enhanced is the crystallinity of the α-Cr{sub 2}O{sub 3} layer. The α-Cr{sub 2}O{sub 3} layer with the Cr underneath it in addition to the photo-induced porosity acted as a classical ceramic–metal nano-composite making the reflectance to decrease significantly within the spectral range of 190–1100 nm. The average reflectance decreased from 70 to 2%.

  19. Synthesis and Characterization of Chromium Oxide Nanoparticles

    Directory of Open Access Journals (Sweden)

    Vivek Sheel Jaswal

    2014-06-01

    Full Text Available Chromium oxide nanoparticles (NPshave been rapidly synthesized by precipitation method using ammomia as precipitating agent and are characterized by using X-ray Diffraction (XRD, Thermo Gravimetric Analysis (TGA, UV-Visible absorption (UV, Infrared Spectoscopy (IR, Scanning Electron Microscopy (SEM and Transmission Electron Microscopy (TEM. XRD studies show that chromium oxide NP is formed as Cr2O3 and it has hexagonal structure. The shape and particle size of the synthesized Cr2O3 NPs is determined by SEM and TEM. The images showed that the size of NPs of Cr2O3 varied from 20 nm to 70 nm with average crystalline size 45 nm. UV-Visible absorption and IR spectoscopy confirm the formation of nanosized Cr2O3. TGA verifies that the Cr2O3 NPs are thermally stable upto 1000 °C.

  20. Chromium isotope composition of reducing and anoxic sediments from the Peru Margin and Cariaco Basin

    Science.gov (United States)

    Gueguen, B.; Planavsky, N.; Wang, X.; Algeo, T. J.; Peterson, L. C.; Reinhard, C. T.

    2014-12-01

    Chromium isotope systematics in marine sediments are now being used as a new redox proxy of the modern and ancient Earth's surface. Chromium is primarily delivered to the oceans by riverine inputs through weathering of Cr(III)-rich minerals present in the continental crust and oxidation of insoluble Cr(III) to soluble Cr(VI) species. Since oxidation-reduction reactions fractionate Cr isotopes whereby oxidized Cr(VI) species are preferentially enriched in heavy Cr isotopes, the Cr isotope composition of marine sediments may be useful tracers of redox conditions at the Earth's surface through geological time. Chromium is quantitatively removed in organic-rich sediments where reducing conditions prevail and promote reduction of Cr(VI) to Cr(III), and thus, these sediments should capture the ambient seawater Cr isotope composition. However, the isotopic composition of modern organic-rich sediments is poorly documented so far, and this step is essential for further modeling the global oceanic Cr isotope mass balance and assessing the effects of sedimentation and post-depositional processes on the marine Cr isotopes archive. In this study, we have characterized modern marine organic-rich sediments for their Cr isotope composition (δ53/52Cr) from two different settings, the Peru margin upwelling zone and the anoxic Cariaco Basin (Venezuela). Chromium isotopes were measured on a MC-ICP-MS (Nu Plasma) using a double-spike correction method. The authigenic fraction of shallow samples from the Peru margin sedimentary sequence with a high Total Organic Carbon (TOC) content (>10 wt%) yield an average δ53/52Crauthigenic value of +0.67 ±0.05 ‰ (2sd). However, although this value is close to the seawater value (Atlantic Ocean) and to Cariaco basin sediments (~ +0.6 ‰), reducing sediments from the Peru margin are on average isotopically slightly heavier, especially in samples having a low authigenic fraction and a low TOC content (δ53/52Crauthigenic values up to +1.30

  1. CHROMIUM(II) AMIDES - SYNTHESIS AND STRUCTURES

    NARCIS (Netherlands)

    EDEMA, JJH; GAMBAROTTA, S; MEETSMA, A; SPEK, AL; SMEETS, WJJ; CHIANG, MY

    1993-01-01

    A novel class of mono- and di-meric chromium(II) amides has been prepared and characterized. Reaction of [CrCl2(thf)2] (thf = tetrahydrofuran) with 2 equivalents of M(NR2) (R = C6H11, Pr(i), Ph, or phenothiazinyl; M = Li or Na) allowed the formation of the homoleptic amides [{Cr(mu-NR2)(NR2)}2] (R =

  2. Stainless chromium-nickel steels. Chapter I

    International Nuclear Information System (INIS)

    The chemical composition is tabulated of 90 chromium-nickel stainless steels and alloys given in volume %. The values are also given of the corrosion resistance of the steels and alloys. The tables show data on the surface condition or the methods of material working, types and chemical composition of the medium where corrosion resistance tests were carried out, temperature, pressure, time of tests, corrosion rates, corrosion types, and literature references. A total of 35 references is given. (J.B.)

  3. Elementary surface processes during reactive magnetron sputtering of chromium

    Energy Technology Data Exchange (ETDEWEB)

    Monje, Sascha; Corbella, Carles, E-mail: carles.corbella@rub.de; Keudell, Achim von [Research Group Reactive Plasmas, Ruhr-University Bochum, Universitystr. 150, 44801 Bochum (Germany)

    2015-10-07

    The elementary surface processes occurring on chromium targets exposed to reactive plasmas have been mimicked in beam experiments by using quantified fluxes of Ar ions (400–800 eV) and oxygen atoms and molecules. For this, quartz crystal microbalances were previously coated with Cr thin films by means of high-power pulsed magnetron sputtering. The measured growth and etching rates were fitted by flux balance equations, which provided sputter yields of around 0.05 for the compound phase and a sticking coefficient of O{sub 2} of 0.38 on the bare Cr surface. Further fitted parameters were the oxygen implantation efficiency and the density of oxidation sites at the surface. The increase in site density with a factor 4 at early phases of reactive sputtering is identified as a relevant mechanism of Cr oxidation. This ion-enhanced oxygen uptake can be attributed to Cr surface roughening and knock-on implantation of oxygen atoms deeper into the target. This work, besides providing fundamental data to control oxidation state of Cr targets, shows that the extended Berg's model constitutes a robust set of rate equations suitable to describe reactive magnetron sputtering of metals.

  4. Dimensionally Controlled Lithiation of Chromium Oxide

    Energy Technology Data Exchange (ETDEWEB)

    Fister, Tim T. [Argonne National Lab. (ANL), Argonne, IL (United States); Hu, Xianyi [Northwestern Univ., Evanston, IL (United States); Esbenshade, Jennifer [Univ. of Illinois, Urbana-Champaign, IL (United States); Chen, Xiao [Northwestern Univ., Evanston, IL (United States); Wu, Jinsong [Northwestern Univ., Evanston, IL (United States); Dravid, Vinayak [Northwestern Univ., Evanston, IL (United States); Bedzyk, Michael [Northwestern Univ., Evanston, IL (United States); Long, Brandon [Argonne National Lab. (ANL), Argonne, IL (United States); Gewirth, Andrew A. [Univ. of Illinois, Urbana-Champaign, IL (United States); Shi, Bing [Argonne National Lab. (ANL), Argonne, IL (United States); Schlepütz, Christian M. [Argonne National Lab. (ANL), Argonne, IL (United States); Fenter, Paul [Argonne National Lab. (ANL), Argonne, IL (United States)

    2016-01-12

    Oxide conversion reactions are an alternative approach for high capacity lithium ion batteries but are known to suffer from structural irreversibility associated with the phase separation and reconstitution of reduced metal species and Li2O. In particular, the morphology of the reduced metal species is thought to play a critical role in the electrochemical properties of a conversion material. Here we use a model electrode with alternating layers of chromium and chromium oxide to better understand and control these phase changes in real-time and at molecular length scales. Despite lacking crystallinity at the atomic scale, this superstructure is observed (with X-ray reflectivity, XR) to lithiate and delithiate in a purely one-dimensional manner, preserving the layered structure. The XR data show that the metal layers act as nucleation sites for the reduction of chromium in the conversion reaction. Irreversibility during delithiation is due to the formation of a ternary phase, LiCrO2, which can be further delithiated at higher potentials. The results reveal that the combination of confining lithiation to nanoscale sheets of Li2O and the availability of reaction sites in the metal layers in the layered structure is a strategy for improving the reversibility and mass transport properties that can be used in a wide range of conversion materials.

  5. Chromium--a material for fusion technology

    International Nuclear Information System (INIS)

    Due to their low neutron-induced radioactivity chromium based materials are considered to be candidates for structure materials in fusion technology. In this paper investigations are presented of unirradiated chromium with a purity of 99.96% (DUCROPUR) and a dispersion strengthened chromium alloy Cr5Fe1Y2O3 (DUCROLLOY). Both materials have been produced in a powder metallurgical route. Mechanical tests of smooth and pre-cracked specimens have been performed in a wide temperature range. Below 280 deg. C the fracture toughness values of DUCROPUR are very low (1/2), above the transition temperature they exceed 500 MPa m1/2. Large plastic deformations have been observed. DUCROLLOY does not indicate such a significant increase of fracture toughness in the tested temperature range. But above 400 deg. C large plastic deformations can be obtained in bending samples, too. The fatigue crack propagation behaviour of DUCROPUR at 300 deg. C is similar to that of a ductile metal

  6. Effect of polyethylene glycol on electrochemically deposited trivalent chromium layers

    Institute of Scientific and Technical Information of China (English)

    Joo-Yul LEE; Man KIM; Sik-Chol KWON

    2009-01-01

    The structural characteristics of the trivalent chromium deposits and their interfacial behavior in the plating solution with and without polyethylene glycol molecules were observed by using various electrochemical methods such as cyclic voltammetry, open circuit potential transition, electrochemical impedance spectroscopy, scanning electron microscopy and X-ray photoelectron spectrometry. It is shown that the polyethylene glycol molecules make the reductive current density lower in the trivalent chromium plating system and promote a hydrogen evolution reaction through their adsorption on the electrode surface. And the trivalent chromium layer formed from the polyethylene glycol-containing solution has somewhat higher density of cracks on its surface and results in a lower film resistance, lower polarization resistance, and higher capacitance in a corrosive atmosphere. It is also revealed that the formation of chromium carbide layer is facilitated in the presence of polyethylene glycol, which means easier electrochemical codeposition of chromium and carbon, not single chromium deposition.

  7. New technology for comprehensive utilization of aluminum-chromium residue from chromium salts production

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-bin; QI Tian-gui; JIANG Xin-min; ZHOU Qiu-sheng; LIU Gui-hua; PENG Zhi-hong; HAN Deng-lun; ZHANG Zhong-yuan; YANG Kun-shan

    2008-01-01

    Colloidal aluminum-chromium residue(ACR) was mass-produced in chromate production process, and the large energy consumption and high recovery cost existed in traditional methods of utilizing such ACR. To overcome those problems, a new comprehensive method was proposed to deal with the ACR, and was proven valid in industry. In the new process, the chromate was separated firstly from the colloidal ACR by ripening and washing with additives, by which more than 95% hexavalent chromium was recovered. The chromium-free aluminum residue(CFAR), after properly dispersed, was digested at 120-130 ℃ and more than 90% alumina can be recovered. And then the pregnant aluminate solution obtained from digestion was seeded to precipitate aluminum hydroxide. This new method can successfully recover both alumina and sodium chromate, and thus realize the comprehensive utilization of ACR from chromate industry.

  8. Analysis of molybdenum, chromium, vanadium and iron by polarographic techniques

    International Nuclear Information System (INIS)

    The application of direct current Tast polarograph, differential pulse polarography and phase-selective alternative current Tast polarography to the problem of determining molybdenum, chromium, vanadium and iron in various supporting electrolytes is reported. The effect of the supporting electrolyte on the wave/peak potential and sensitivity of the metal ion have been examined. The polarographic methods were applied for simultaneous determination of chromium (3)/chromium (6), vanadium (4), vanadium (5) and iron (2)/iron (3) in different supporting electrolytes

  9. A REVIEW OF BIOSORPTION OF CHROMIUM IONS BY MICROORGANISMS

    OpenAIRE

    Inga Zinicovscaia

    2012-01-01

    Due to its widespread industrial use, chromium has become a serious pollutant in diverse environmental settings. The main source of chromium pollution including the Republic o Moldova is industry. It is a great need to develop new eco-friendly methods of chromium removal. Biosorption of heavy metals is a most promising technology involved in the removal of toxic metals from industrial waste streams and natural waters. This article is an extended abstract of a communication presented at the...

  10. CHROMIUM INDUCED CYTOTOXICITY IN BLACKGRAM (VIGNA MUNGO L.)

    OpenAIRE

    A. Chidambaram ، P. Sundaramoorthy ، A. Murugan ، K. Sankar Ganesh ، L. Baskaran

    2009-01-01

    Chromium is known to be highly toxic to biological systems. This study was designed to determine the mutagenic effects of different concentrations (0, 10, 25, 50, 100 and 200 mg/L) of hexavalent chromium on root tip cells of blackgram (Vigna mungo L. Hepper). The blackgram seeds were equi-spacially arranged in sterilized petriplates lined with filter paper and they were treated with different concentrations of chromium solution. In germination studies, the morphological growth parameters such...

  11. Processes affecting the remediation of chromium-contaminated sites.

    OpenAIRE

    Palmer, C.D.; Wittbrodt, P R

    1991-01-01

    The remediation of chromium-contaminated sites requires knowledge of the processes that control the migration and transformation of chromium. Advection, dispersion, and diffusion are physical processes affecting the rate at which contaminants can migrate in the subsurface. Heterogeneity is an important factor that affects the contribution of each of these mechanisms to the migration of chromium-laden waters. Redox reactions, chemical speciation, adsorption/desorption phenomena, and precipitat...

  12. Production of a chromium Bose-Einstein condensate

    OpenAIRE

    Griesmaier, Axel; Stuhler, Jürgen; Pfau, Tilman

    2005-01-01

    The recent achievement of Bose-Einstein condensation of chromium atoms [1] has opened longed-for experimental access to a degenerate quantum gas with long-range and anisotropic interaction. Due to the large magnetic moment of chromium atoms of 6 {$\\mu$}B, in contrast to other Bose- Einstein condensates (BECs), magnetic dipole-dipole interaction plays an important role in a chromium BEC. Many new physical properties of degenerate gases arising from these magnetic forces have been predicted in ...

  13. Increase of chromium utilization in stainless steel melting

    International Nuclear Information System (INIS)

    The processes of deoxidizing when melting stainless 18-10 steels in electric are furnaces by the method of remelting with wastes are investigated. The dependences of amount of reduced chromium on silicon consumption are made more precise. It is shown that it is useful to apply aluminium for deoxidation of acid high-chromium slags. Based on the data on pilot melts the extent to which aluminium can be used as a reducing agent for chromium is estimated. 3 refs., 2 figs

  14. Full p53 transcriptional activation potential is dispensable for tumor suppression in diverse lineages.

    Science.gov (United States)

    Jiang, Dadi; Brady, Colleen A; Johnson, Thomas M; Lee, Eunice Y; Park, Eunice J; Scott, Matthew P; Attardi, Laura D

    2011-10-11

    Over half of all human cancers, of a wide variety of types, sustain mutations in the p53 tumor suppressor gene. Although p53 limits tumorigenesis through the induction of apoptosis or cell cycle arrest, its molecular mechanism of action in tumor suppression has been elusive. The best-characterized p53 activity in vitro is as a transcriptional activator, but the identification of numerous additional p53 biochemical activities in vitro has made it unclear which mechanism accounts for tumor suppression. Here, we assess the importance of transcriptional activation for p53 tumor suppression function in vivo in several tissues, using a knock-in mouse strain expressing a p53 mutant compromised for transcriptional activation, p53(25,26). p53(25,26) is severely impaired for the transactivation of numerous classical p53 target genes, including p21, Noxa, and Puma, but it retains the ability to activate a small subset of p53 target genes, including Bax. Surprisingly, p53(25,26) can nonetheless suppress tumor growth in cancers derived from the epithelial, mesenchymal, central nervous system, and lymphoid lineages. Therefore, full transactivation of most p53 target genes is dispensable for p53 tumor suppressor function in a range of tissue types. In contrast, a transcriptional activation mutant that is completely defective for transactivation, p53(25,26,53,54), fails to suppress tumor development. These findings demonstrate that transcriptional activation is indeed broadly critical for p53 tumor suppressor function, although this requirement reflects the limited transcriptional activity observed with p53(25,26) rather than robust transactivation of a full complement of p53 target genes.

  15. Nuclear accumulation and activation of p53 in embryonic stem cells after DNA damage

    Directory of Open Access Journals (Sweden)

    Rolletschek Alexandra

    2009-06-01

    Full Text Available Abstract Background P53 is a key tumor suppressor protein. In response to DNA damage, p53 accumulates to high levels in differentiated cells and activates target genes that initiate cell cycle arrest and apoptosis. Since stem cells provide the proliferative cell pool within organisms, an efficient DNA damage response is crucial. Results In proliferating embryonic stem cells, p53 is localized predominantly in the cytoplasm. DNA damage-induced nuclear accumulation of p53 in embryonic stem cells activates transcription of the target genes mdm2, p21, puma and noxa. We observed bi-phasic kinetics for nuclear accumulation of p53 after ionizing radiation. During the first wave of nuclear accumulation, p53 levels were increased and the p53 target genes mdm2, p21 and puma were transcribed. Transcription of noxa correlated with the second wave of nuclear accumulation. Transcriptional activation of p53 target genes resulted in an increased amount of proteins with the exception of p21. While p21 transcripts were efficiently translated in 3T3 cells, we failed to see an increase in p21 protein levels after IR in embryonal stem cells. Conclusion In embryonic stem cells where (anti-proliferative p53 activity is not necessary, or even unfavorable, p53 is retained in the cytoplasm and prevented from activating its target genes. However, if its activity is beneficial or required, p53 is allowed to accumulate in the nucleus and activates its target genes, even in embryonic stem cells.

  16. Absence of tumor suppressor tumor protein 53-induced nuclear protein 1 (TP53INP1) sensitizes mouse thymocytes and embryonic fibroblasts to redox-driven apoptosis.

    Science.gov (United States)

    N'guessan, Prudence; Pouyet, Laurent; Gosset, Gaëlle; Hamlaoui, Sonia; Seillier, Marion; Cano, Carla E; Seux, Mylène; Stocker, Pierre; Culcasi, Marcel; Iovanna, Juan L; Dusetti, Nelson J; Pietri, Sylvia; Carrier, Alice

    2011-09-15

    The p53-transcriptional target TP53INP1 is a potent stress-response protein promoting p53 activity. We previously showed that ectopic overexpression of TP53INP1 facilitates cell cycle arrest as well as cell death. Here we report a study investigating cell death in mice deficient for TP53INP1. Surprisingly, we found enhanced stress-induced apoptosis in TP53INP1-deficient cells. This observation is underpinned in different cell types in vivo (thymocytes) and in vitro (thymocytes and MEFs), following different types of injury inducing either p53-dependent or -independent cell death. Nevertheless, absence of TP53INP1 is unable to overcome impaired cell death of p53-deficient thymocytes. Stress-induced ROS production is enhanced in the absence of TP53INP1, and antioxidant NAC complementation abolishes increased sensitivity to apoptosis of TP53INP1-deficient cells. Furthermore, antioxidant defenses are defective in TP53INP1-deficient mice in correlation with ROS dysregulation. Finally, we show that autophagy is reduced in TP53INP1-deficient cells both at the basal level and upon stress. Altogether, these data show that impaired ROS regulation in TP53INP1-deficient cells is responsible for their sensitivity to induced apoptosis. In addition, they suggest that this sensitivity could rely on a defect of autophagy. Therefore, these data emphasize the role of TP53INP1 in protection against cell injury.

  17. Optical-scattering measurements from 1.06-μm, 0.53-μm, and 0.35-μm laser-heated disk targets

    International Nuclear Information System (INIS)

    A discussion is presented on scattered light measurements relevant to three of the important parametric instabilities which occur in high intensity laser plasma interactions: stimulated Brillouin scattering (SBS), the two plasmon decay instability (2-ω/sub pe/), and stimulated Raman scattering (SRS). Most of these experiments were carried out on the ARGUS facility. Its configuration is described for the multiple wavelength experiments, all of which were conducted with one beam illumination of flat disk targets

  18. Chromium depletion from stainless steels during vacuum annealing

    International Nuclear Information System (INIS)

    The behaviour of chromium during selective evaporation by high temperature vacuum annealing has been investigated by means of energy dispersive X-ray analysis and by neutron activation analysis. It was established that the rate of chromium loss from austenitic stainless steels 316 and 321 is controlled by chromium inter-diffusion rather than tracer diffusion in the alloy. Two important parameters in selective removal of chromium from alloy steels are the variation in the chromium surface concentration with time and the depletion profile in the alloy. The present work gives support for the model in which loss of chromium is dependent on its diffusivity in the alloy and on an interface transfer coefficient. The results showed that the surface concentration of chromium decreased with increasing vacuum annealing time. The chromium depletion profile in the metal was in accord with the previous derived model, apart from an anomalous near surface region. Here the higher resolution of a neutron activation technique indicated a region within approximately 2 microns of the surface where the chromium concentration decreased more steeply than expected. (author)

  19. Stabilization and solidification of chromium-contaminated soil

    Energy Technology Data Exchange (ETDEWEB)

    Cherne, C.A.; Thomson, B.M. [Univ. of New Mexico, Albuquerque, NM (United States). Civil Engineering Dept.; Conway, R. [Sandia National Labs., Albuquerque, NM (United States)

    1997-11-01

    Chromium-contaminated soil is a common environmental problem in the United States as a result of numerous industrial processes involving chromium. Hexavalent chromium [Cr(VI)] is the species of most concern because of its toxicity and mobility in groundwater. One method of diminishing the environmental impact of chromium is to reduce it to a trivalent oxidation state [Cr(III)], in which it is relatively insoluble and nontoxic. This study investigated a stabilization and solidification process to minimize the chromium concentration in the Toxicity Characteristic Leaching Procedure (TCLP) extract and to produce a solidified waste form with a compressive strength in the range of 150 to 300 pounds per square inch (psi). To minimize the chromium in the TCLP extract, the chromium had to be reduced to the trivalent oxidation state. The average used in this study was an alluvium contaminated with chromic and sulfuric acid solutions. The chromium concentration in the in the in situ soil was 1212 milligrams per kilogram (mg/kg) total chromium and 275 mg/kg Cr(VI). The effectiveness of iron, ferrous sulfate to reduce Cr(VI) was tested in batch experiments.

  20. Defect transformation in GSGG crystals during chromium ion activation

    International Nuclear Information System (INIS)

    Absorption and induced absorption spectra, dose dependence of induced absorption, thermoluminescence of GSGG crystals, nominally pure and activated with chromium and neodymium ions in different concentrations, are investigated. It is shown that it is chromium ion presence in large concentration that decreases the induced coloration in GSGG crystals after γ-irradiation at 300 K. Optimum concentration of chromium ions for the minimum of induced coloration are found. The mechanism of decrease of induced coloration consisting in Fermi level displacement by chromium ion activation is established. Defect concentration and localization and recombination possibilities of electrons and holes in GSGG crystals are estimated by computer simulation

  1. Tribological Characteristics of Chromium-active Carbon Electroplated Composite Coatings

    Institute of Scientific and Technical Information of China (English)

    GUKa-fi; HUAMeng; Yi-min

    2004-01-01

    A process of chromium electroplating using a standard bath with additives and active carbon particles was reported, and the tribological behaviors of the composite coatings using the pin-on-disk tester and the table wear tester were i nvestig(aed. Experimental results indicate that the electroplated chromium-active carbon composite coatings exhibited the low friction coefficient anti excellent anti-wear properties whets coffered with the normal chromium electroplated ones. The formation of active carbon particles within the chromium matrices can be explained by SEM analysis and the mechanis of wear resistance of the composite coatings were studied.

  2. Method of trivalent chromium concentration determination by atomic spectrometry

    Science.gov (United States)

    Reheulishvili, Aleksandre N.; Tsibakhashvili, Neli Ya.

    2006-12-12

    A method is disclosed for determining the concentration of trivalent chromium Cr(III) in a sample. The addition of perchloric acid has been found to increase the atomic chromium spectrometric signal due to Cr(III), while leaving the signal due to hexavalent chromium Cr(VI) unchanged. This enables determination of the Cr(III) concentration without pre-concentration or pre-separation from chromium of other valences. The Cr(III) concentration may be measured using atomic absorption spectrometry, atomic emission spectrometry or atomic fluorescence spectrometry.

  3. Influence of Chelating Agents on Chromium Fate in Sediment

    Institute of Scientific and Technical Information of China (English)

    WANGXIAOCHANG; SUNJINHE; 等

    1996-01-01

    A laboratory investigation on reaction between chelating agents and chromium was conducted to evaluate the effect of chelating agents on the adsorption and desorption of chromium in sediment.The amount of adsorbed chromium(VI) in sediment decreased slightly by 5%-10% because of addition of chelating agents.Chelating agents inhibited the removal of Cr(Ⅲ)by sediment from solutions and the inhibiting effect was in the order:citric acid>tartaric acid>EDTA,Salicylic acid.No effect of chelating agents on desorption of chromium in sediment was observed.

  4. Ferrous sulphate mono and heptahydrate reduction of hexavalent chromium in cement: effectiveness and storability

    Directory of Open Access Journals (Sweden)

    Valverde, J. L.

    2005-09-01

    Full Text Available In Community legislation, substances containing hexavalent chromium are classified as carcinogenic, mutagenic and sensitizing. In cement, hexavalent chromium intensifies sensitization and may set off severe allergic reactions in workers in routine contact with the product, whether in the factory or on construction sites. The allergic or contact dermatitis causes is a very painful disease that may lead to permanent worker disability. According to Directive 2003/53/EC of the European Parliament and the Council, Governments of all member countries will be required to prohibit the marketing and use, as of 17 January 2005, of any cement or cement preparation containing more than 2 ppm of chromium (VI. Hexavalent chromium can be reduced with ferrous sulphate to trivalent chromium, which is water-insoluble and therefore innocuous to the skin. The present paper reports the effects of adding ferrous sulphate mono- or heptahydrate to a commercial cement and the storage time of the mix on the concentration of hexavalent chromium. The salts studied were found to effectively reduce hexavalent chromium in cement for at least three months.

    Las sustancias que contienen cromo hexavalente están clasificadas en la legislación comunitaria como sustancias carcinogénicas, mutagénicas y sensibilizantes. El cromo hexavalente del cemento potencia la sensibilización y provoca graves reacciones alérgicas que sufren bastante a menudo los trabajadores que lo manipulan habitualmente, ya sea en fábrica o en el sector de la construcción. La dermatitis alérgica o de contacto que produce es muy dolorosa y puede dejar a los trabajadores en estado de discapacidad. La Directiva 2003/53/CE del Parlamento Europeo y del Consejo, exige a los Gobiernos de los países miembros, que a partir del 17 de enero de 2005, prohiban el uso y la comercialización de todos aquellos cementos y preparados que contengan cemento, cuyo contenido en cromo (VI soluble, una vez hidratados

  5. Fluctuations in Precambrian atmospheric oxygenation recorded by chromium isotopes.

    Science.gov (United States)

    Frei, Robert; Gaucher, Claudio; Poulton, Simon W; Canfield, Don E

    2009-09-10

    Geochemical data suggest that oxygenation of the Earth's atmosphere occurred in two broad steps. The first rise in atmospheric oxygen is thought to have occurred between approximately 2.45 and 2.2 Gyr ago, leading to a significant increase in atmospheric oxygen concentrations and concomitant oxygenation of the shallow surface ocean. The second increase in atmospheric oxygen appears to have taken place in distinct stages during the late Neoproterozoic era ( approximately 800-542 Myr ago), ultimately leading to oxygenation of the deep ocean approximately 580 Myr ago, but details of the evolution of atmospheric oxygenation remain uncertain. Here we use chromium (Cr) stable isotopes from banded iron formations (BIFs) to track the presence of Cr(VI) in Precambrian oceans, providing a time-resolved picture of the oxygenation history of the Earth's atmosphere-hydrosphere system. The geochemical behaviour of Cr is highly sensitive to the redox state of the surface environment because oxidative weathering processes produce the oxidized hexavalent [Cr(VI)] form. Oxidation of reduced trivalent [Cr(III)] chromium on land is accompanied by an isotopic fractionation, leading to enrichment of the mobile hexavalent form in the heavier isotope. Our fractionated Cr isotope data indicate the accumulation of Cr(VI) in ocean surface waters approximately 2.8 to 2.6 Gyr ago and a likely transient elevation in atmospheric and surface ocean oxygenation before the first great rise of oxygen 2.45-2.2 Gyr ago (the Great Oxidation Event). In approximately 1.88-Gyr-old BIFs we find that Cr isotopes are not fractionated, indicating a decline in atmospheric oxygen. Our findings suggest that the Great Oxidation Event did not lead to a unidirectional stepwise increase in atmospheric oxygen. In the late Neoproterozoic, we observe strong positive fractionations in Cr isotopes (delta(53)Cr up to +4.9 per thousand), providing independent support for increased surface oxygenation at that time, which may

  6. Trans-splicing repair of mutant p53 suppresses the growth of hepatocellular carcinoma cells in vitro and in vivo

    OpenAIRE

    Xingxing He; Fang Liu; Jingjun Yan; Yunan Zhang; Junwei Yan; Haitao Shang; Qian Dou; Qiu Zhao; Yuhu Song

    2015-01-01

    Reactivation of wild-type p53 (wt-p53) function is an attractive therapeutic approach to p53-defective cancers. An ideal p53-based gene therapy should restore wt-p53 production and reduces mutant p53 transcripts simultaneously. In this study, we described an alternative strategy named as trans-splicing that repaired mutant p53 transcripts in hepatocellular carcinoma (HCC) cells. The plasmids which encoded a pre-trans-splicing molecule (PTM) targeting intron 6 of p53 were constructed and then ...

  7. Mdm2 is required for survival of hematopoietic stem cells/progenitors via dampening of ROS-induced p53 activity

    Science.gov (United States)

    Mdm2 is an E3 ubiquitin ligase that targets p53 for degradation. p53(515C) (encoding p53R172P) is a hypomorphic allele of p53 that rescues the embryonic lethality of Mdm2(-/-) mice. Mdm2(-/-) p53(515C/515C) mice, however, die by postnatal day 13 resulting from hematopoietic failure. Hematopoietic st...

  8. p53 gene in treatment of hepatic carcinoma:Status quo

    Institute of Scientific and Technical Information of China (English)

    Yong-Song Guan; Zi La; Lin Yang; Qing He; Ping Li

    2007-01-01

    Hepatocellular carcinoma(HCC)is one of the 10 most common cancers worldwide.There is no ideal treatment for HCC yet and many researchers are trying to improve the effects of treatment by changing therapeutic strategies.As the majority of human cancers seem to exhibit either abnormal p53 gene or disrupted p53 gene activation pathways,intervention to restore wild-type p53 (wt-p53)activities is an attractive anti-cancer therapy including HCC.Abnormalities of p53 are also considered a predisposition factor for hepatocarcinogenesis.p53 is frequently mutated in HCC.Most HCCs have defects in the p53-mediated apoptotic pathway although they carry wt-p53.High expression of p53 in vivo may exert therapeutic effects on HCC in two aspects:(1)High expression of exogenous p53 protein induces apoptosis of tumor cells by inhibiting proliferation of cells through several biologic pathways and(2)Exogenous p53 renders HCC more sensitive to some chemotherapeutic agents.Several approaches have been designed for the treatment of HCC via the p53 pathway by restoring the tumor suppression function from inactivation,rescuing the mutated p53 gene from instability,or delivering therapeutic exogenous p53.Products with p53 status as the target have been studied extensively in vitro and in vivo.This review elaborates some therapeutic mechanisms and advances in using recombinant human adenovirus p53 and oncolytic virus products for the treatment of HCC.

  9. p53 isoforms regulate astrocyte-mediated neuroprotection and neurodegeneration.

    Science.gov (United States)

    Turnquist, C; Horikawa, I; Foran, E; Major, E O; Vojtesek, B; Lane, D P; Lu, X; Harris, B T; Harris, C C

    2016-09-01

    Bidirectional interactions between astrocytes and neurons have physiological roles in the central nervous system and an altered state or dysfunction of such interactions may be associated with neurodegenerative diseases, such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Astrocytes exert structural, metabolic and functional effects on neurons, which can be either neurotoxic or neuroprotective. Their neurotoxic effect is mediated via the senescence-associated secretory phenotype (SASP) involving pro-inflammatory cytokines (e.g., IL-6), while their neuroprotective effect is attributed to neurotrophic growth factors (e.g., NGF). We here demonstrate that the p53 isoforms Δ133p53 and p53β are expressed in astrocytes and regulate their toxic and protective effects on neurons. Primary human astrocytes undergoing cellular senescence upon serial passaging in vitro showed diminished expression of Δ133p53 and increased p53β, which were attributed to the autophagic degradation and the SRSF3-mediated alternative RNA splicing, respectively. Early-passage astrocytes with Δ133p53 knockdown or p53β overexpression were induced to show SASP and to exert neurotoxicity in co-culture with neurons. Restored expression of Δ133p53 in near-senescent, otherwise neurotoxic astrocytes conferred them with neuroprotective activity through repression of SASP and induction of neurotrophic growth factors. Brain tissues from AD and ALS patients possessed increased numbers of senescent astrocytes and, like senescent astrocytes in vitro, showed decreased Δ133p53 and increased p53β expression, supporting that our in vitro findings recapitulate in vivo pathology of these neurodegenerative diseases. Our finding that Δ133p53 enhances the neuroprotective function of aged and senescent astrocytes suggests that the p53 isoforms and their regulatory mechanisms are potential targets for therapeutic intervention in neurodegenerative diseases. PMID:27104929

  10. Alpha-emitting isotopes and chromium in a coastal California aquifer

    International Nuclear Information System (INIS)

    Highlights: • Alluvium in Piedra de Lumbre basin higher radionuclides likely from natural Th. • Natural uranium decay-chain isotopes, including Ra, present in marine deposits. • Marine deposits also contain low concentrations of chromium. • Radionuclides and chromium concentrations lower in alluvium in the Las Flores basin. - Abstract: The unadjusted 72-h gross alpha activities in water from two wells completed in marine and alluvial deposits in a coastal southern California aquifer 40 km north of San Diego were 15 and 25 picoCuries per liter (pCi/L). Although activities were below the Maximum Contaminant Level (MCL) of 15 pCi/L, when adjusted for uranium activity; there is concern that new wells in the area may exceed MCLs, or that future regulations may limit water use from the wells. Coupled well-bore flow and depth-dependent water-quality data collected from the wells in 2011 (with analyses for isotopes within the uranium, actinium, and thorium decay-chains) show gross alpha activity in marine deposits is associated with decay of naturally-occurring 238U and its daughter 234U. Radon activities in marine deposits were as high as 2230 pCi/L. In contrast, gross alpha activities in overlying alluvium within the Piedra de Lumbre watershed, eroded from the nearby San Onofre Hills, were associated with decay of 232Th, including its daughter 224Ra. Radon activities in alluvium from Piedra de Lumbre of 450 pCi/L were lower than in marine deposits. Chromium VI concentrations in marine deposits were less than the California MCL of 10 μg/L (effective July 1, 2014) but δ53Cr compositions were near zero and within reported ranges for anthropogenic chromium. Alluvial deposits from the nearby Las Flores watershed, which drains a larger area having diverse geology, has low alpha activities and chromium as a result of geologic and geochemical conditions and may be more promising for future water-supply development

  11. IRIS Toxicological Review of Hexavalent Chromium (2010 External Review Draft)

    Science.gov (United States)

    [UPDATE] New Schedule for IRIS Hexavalent Chromium Assessment In Feb 2012, EPA developed a new schedule for completing the IRIS hexavalent chromium assessment. Based on the recommendations of the external peer review panel, which met in May 2011 to review the dra...

  12. Chromium and Polyphenols From Cinnamon Improve Insulin Sensitivity

    Science.gov (United States)

    Naturally occurring compounds that have been shown to improve insulin sensitivity include chromium and polyphenols found in cinnamon. These compounds also have similar effects on insulin signaling and glucose control. The signs of chromium deficiency are similar to those for the metabolic syndrome ...

  13. Safety, absorption, and antioxidant effects of chromium histidine

    Science.gov (United States)

    Supplemental chromium has been shown to be involved in the alleviation of the metabolic syndrome, glucose intolerance, polycystic ovary syndrome, depression, excess body fat, and gestational, steroid-induced, and type 2 diabetes. Chromium amino acid complexes that contained histidine displayed cons...

  14. Toxicity and adaptation of Dictyosphaerium chlorelloides to extreme chromium contamination.

    Science.gov (United States)

    Sánchez-Fortún, Sebastián; López-Rodas, Victoria; Navarro, Macarena; Marvá, Fernando; D'ors, Ana; Rouco, Mónica; Haigh-Florez, David; Costas, Eduardo

    2009-09-01

    Metals are often spilled by industries into inland water environments, with adverse consequences. Numerous papers have reported that heavy metals produce massive destruction of algae. Nevertheless, algal populations seem to become tolerant when they have had previous exposures to heavy metals. Because the mechanisms allowing heavy metal tolerance of algae are not yet known, the present study analyzed the effect of hexavalent chromium on growth and photosynthetic performance of Dictyosphaerium chlorelloides, stressing on the adaptation mechanisms to chromium contamination. Growth and photosynthetic performance of algal cells were inhibited by Cr(VI) at 10 mg/L, and the 72-h median inhibition concentration was established as 1.64 and 1.54 mg/L, respectively. However, after further incubation for a three month period in an environment with 25 mg/L of chromium, some rare, chromium-resistant cells occasionally were found. A Luria-Delbrück fluctuation analysis was performed to distinguish between resistant algae arising from rare, spontaneous mutations and resistant algae arising from physiological adaptation and other adaptive mechanisms. Resistant cells arose only by spontaneous mutations before the addition of chromium, with a rate of 1.77 x 10(-6) mutants per cell division. From a practical point of view, the use of both chromium-sensitive and chromium-resistant genotypes could make possible a specific algal biosensor for chromium. PMID:19323601

  15. Residual Chromium in Leather by Instrumental Neutron Activation Analysis

    Directory of Open Access Journals (Sweden)

    S. Okoh

    2012-01-01

    Full Text Available Problem statement: Most tanning processes employ the use of chromium sulphate. For chromium tanned leather, finished products may contain high amount of residual chromium. This may pose some health hazards, since chromium is known to be toxic at elevated concentration. This justifies the need for the study. Approach: Various samples of leather were collected from a tannery, a leather crafts market, a leather dump site and from local tanners all in Kano, Nigeria in 2009. The samples were irradiated for 6 h in the inner site of the Nigerian Research Reactor (NIRR-1 at a flux of 5×1011 ncm-2 sec-1. Results: After evaluating the spectrum, the mean results for chromium in the samples were determined as 2.33±0.3, 2.23±0.3 and 2.93±0.4% for samples from the tannery, leather crafts market and leather dump sites respectively. Chromium concentration in samples collected from local tanners who use tannins from Acacia nilotica as tanning agent was below the detection limit of Instrumental Neutron Activation Analysis (INAA technique used in the study. Conclusion: Although, the concentrations of chromium in the analysed samples were not much higher than what were obtained in literature, they may be enough to sensitize the population that is allergic to chromium.

  16. Effects of p53 knockout on ochratoxin A-induced genotoxicity in p53-deficient gpt delta mice.

    Science.gov (United States)

    Hibi, Daisuke; Kijima, Aki; Suzuki, Yuta; Ishii, Yuji; Jin, Meilan; Sugita-Konishi, Yoshiko; Yanai, Tokuma; Nishikawa, Akiyoshi; Umemura, Takashi

    2013-02-01

    Ochratoxin A (OTA) is a mycotoxin produced by fungal species and is carcinogenic targeting the S3 segment of the renal proximal tubules in rodents. We previously reported that exposure of gpt delta rats to OTA induced both mutations in the red/gam gene (Spi(-)), suggesting large deletion mutations, and fluctuations in genes transcribed by p53 in the kidneys, which were associated with DNA double-strand break (DSB) repair, particularly homologous recombination (HR) repair. In the present study, to investigate the effects of p53 knockout on OTA-induced mutagenicity, apoptosis, and karyomegaly in renal tubular cells, p53-proficient and p53-deficient gpt delta mice were given 1 and 5mg/kg of OTA for 4 weeks. Significant increases in Spi(-) mutant frequencies (MFs) were observed in the kidneys of p53-deficient gpt delta mice given 5 mg/kg of OTA, but not in the kidneys of p53-proficient gpt delta mice given the same dose. There were no changes in gpt MFs in both genotypes of mice treated with OTA. Western blotting analysis demonstrated that p53 protein levels in the kidneys of p53-proficient mice given OTA were significantly increased compared with the control. Incidences of apoptosis and karyomegaly in not only the outer stripe of outer medulla but also the cortex were significantly higher in p53-deficient at 5mg/kg than in p53-proficient gpt delta mice at same dose, which had no change in the cortex, the inner stripe of outer stripe, and the inner medulla. Given that p53 regulates HR repair in DSBs, these results suggest that OTA may promote large deletion mutations in the process of HR repair for DSBs. Additionally, the lower incidence of karyomegaly and apoptosis found in the p53-proficient gpt delta mice suggests that these phenomena may arise from OTA-induced DNA damage.

  17. CHROMIUM BIOACCUMULATION FROM COMPOSTS AND VERMICOMPOSTS BASED ON TANNERY SLUDGES

    Directory of Open Access Journals (Sweden)

    Krzysztof GONDEK

    2008-07-01

    Full Text Available Storage of waste substances is not indifferent to ecological equilibrium in the environment therefore should not be the ultimate way to limit waste arduousness. Therefore, the conducted investigations aimed to determine the effect of tannery composts and vermicomposts loaded with chromium on this element bioaccumulation in earthworm bodies and biomass of selected plants. Chromium in composts and vermicomposts based on tannery sludges occurred in small quantities and easily soluble compounds. Chromium concentrations in redworm biomass points to this metal accumulation in Eisenia fetida body tissues. This element content in redworm biomass was signifi cantly positively correlated with its content in composts. Chromium content in plants was diversifi ed and on treatments was generally smaller than on mineral treatment or farmyard manure. Chromium absorbed by plants was stored mainly in the root systems, and over the norm content of this element found in vermicomposts did not cause its excessive accumulation in plant biomass.

  18. Bioleaching of chromium from tannery sludge by indigenous Acidithiobacillus thiooxidans.

    Science.gov (United States)

    Wang, Yuan-Shan; Pan, Zhi-Yan; Lang, Jian-Min; Xu, Jian-Miao; Zheng, Yu-Guo

    2007-08-17

    Chromium in tannery sludge will cause serious environmental problems and is toxic to organisms. The acidophilic sulfur-oxidizing Acidithiobacillus thiooxidans can leach heavy metals form urban and industrial wastes. This study examined the ability of an indigenous sulfur-oxidizing A. thiooxidans to leach chromium from tannery sludge. The results showed that the pH of sludge mixture inoculated with the indigenous A. thiooxidans decreased to around 2.0 after 4 days. After 6 days incubation in shaking flasks at 30 degrees C and 160 rpm, up to 99% of chromium was solubilized from tannery sludge. When treated in a 2-l bubble column bioreactor for 5 days at 30 degrees C and aeration of 0.5 vvm, 99.7% of chromium was leached from tannery sludge. The results demonstrated that chromium in tannery sludge can be efficiently leached by the indigenous A. thiooxidans.

  19. Biosorption potency of Aspergillus niger for removal of chromium (VI).

    Science.gov (United States)

    Srivastava, Shaili; Thakur, Indu Shekhar

    2006-09-01

    Aspergillus niger isolated from soil and effluent of leather tanning mills had higher activity to remove chromium. The potency of Aspergillus niger was evaluated in shake flask culture by absorption of chromium at pH 6 and temperature 30 degrees C. The results of the study indicated removal of more than 75% chromium by Aspergillus niger determined by diphenylcarbazide colorimetric assay and atomic absorption spectrophotometry after 7 days. Study of microbial Cr(VI) reduction and identification of reduction intermediates has been hindered by the lack of analytical techniques that can identify the oxidation state with subcellular spatial resolution. Therefore, removal of chromium was further substantiated by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX), which indicated an accumulation of chromium in the fungal mycelium. PMID:16874547

  20. Escape from p53-mediated tumor surveillance in neuroblastoma: switching off the p14(ARF)-MDM2-p53 axis.

    Science.gov (United States)

    Van Maerken, T; Vandesompele, J; Rihani, A; De Paepe, A; Speleman, F

    2009-12-01

    A primary failsafe program against unrestrained proliferation and oncogenesis is provided by the p53 tumor suppressor protein, inactivation of which is considered as a hallmark of cancer. Intriguingly, mutations of the TP53 gene are rarely encountered in neuroblastoma tumors, suggesting that alternative p53-inactivating lesions account for escape from p53 control in this childhood malignancy. Several recent studies have shed light on the mechanisms by which neuroblastoma cells circumvent the p53-driven antitumor barrier. We review here these mechanisms for evasion of p53-mediated growth control and conclude that deregulation of the p14(ARF)-MDM2-p53 axis seems to be the principal mode of p53 inactivation in neuroblastoma, opening new perspectives for targeted therapeutic intervention. PMID:19779493

  1. Nuclear accumulation and activation of p53 in embryonic stem cells after DNA damage

    OpenAIRE

    Rolletschek Alexandra; Solozobova Valeriya; Blattner Christine

    2009-01-01

    Abstract Background P53 is a key tumor suppressor protein. In response to DNA damage, p53 accumulates to high levels in differentiated cells and activates target genes that initiate cell cycle arrest and apoptosis. Since stem cells provide the proliferative cell pool within organisms, an efficient DNA damage response is crucial. Results In proliferating embryonic stem cells, p53 is localized predominantly in the cytoplasm. DNA damage-induced nuclear accumulation of p53 in embryonic stem cells...

  2. p53 aerobics: the major tumor suppressor fuels your workout.

    Science.gov (United States)

    Kruse, Jan-Philipp; Gu, Wei

    2006-07-01

    In addition to its role as the central regulator of the cellular stress response, p53 can regulate aerobic respiration via the novel transcriptional target SCO2, a critical regulator of the cytochrome c oxidase complex (Matoba et al., 2006). Loss of p53 results in decreased oxygen consumption and aerobic respiration and promotes a switch to glycolysis, thereby reducing endurance during physical exercise. PMID:16814724

  3. P53 Mdm2 Inhibitors

    NARCIS (Netherlands)

    Khoury, Kareem; Doemling, Alex

    2012-01-01

    The protein-protein interaction (PPI) between p53 and its negative regulator MDM2 comprises one of the most important and intensely studied PPI's involved in preventing the initiation of cancer. The interaction between p53 and MDM2 is conformation-based and is tightly regulated on multiple levels. D

  4. p53 in stem cells

    Institute of Scientific and Technical Information of China (English)

    Valeriya; Solozobova; Christine; Blattner

    2011-01-01

    p53 is well known as a "guardian of the genome" for differentiated cells,in which it induces cell cycle arrest and cell death after DNA damage and thus contributes to the maintenance of genomic stability.In addition to this tumor suppressor function for differentiated cells,p53 also plays an important role in stem cells.In this cell type,p53 not only ensures genomic integrity after genotoxic insults but also controls their proliferation and differentiation.Additionally,p53 provides an effective barrier for the generation of pluripotent stem celllike cells from terminally differentiated cells.In this review,we summarize our current knowledge about p53 activities in embryonic,adult and induced pluripotent stem cells.

  5. Stochastic modeling of p53-regulated apoptosis upon radiation damage

    CERN Document Server

    Bhatt, Divesh; Bahar, Ivet

    2011-01-01

    We develop and study the evolution of a model of radiation induced apoptosis in cells using stochastic simulations, and identified key protein targets for effective mitigation of radiation damage. We identified several key proteins associated with cellular apoptosis using an extensive literature survey. In particular, we focus on the p53 transcription dependent and p53 transcription independent pathways for mitochondrial apoptosis. Our model reproduces known p53 oscillations following radiation damage. The key, experimentally testable hypotheses that we generate are - inhibition of PUMA is an effective strategy for mitigation of radiation damage if the treatment is administered immediately, at later stages following radiation damage, inhibition of tBid is more effective.

  6. CN Bimodality at Low Metallicity: The Globular Cluster M53

    OpenAIRE

    Martell, Sarah L.; Smith, Graeme H.; Briley, Michael M.

    2007-01-01

    We present low resolution UV-blue spectroscopic observations of red giant stars in the globular cluster M53 ([Fe/H]=-1.84), obtained to study primordial abundance variations and deep mixing via the CN and CH absorption bands. The metallicity of M53 makes it an attractive target: a bimodal distribution of 3883 angstrom CN bandstrength is common in moderate- and high-metallicity globular clusters ([Fe/H] > -1.6) but unusual in those of lower metallicity ([Fe/H] < -2.0). We find that M53 is an i...

  7. The effect of adenovirus expressing wild-type p53 on 5-fiuorouracil chemosensitivity is related to p53 status in pancreatic cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Sven Eisold; Michael Linnebacher; Eduard Ryschich; Dalibor Antolovic; Ulf Hinz; Ernst Klar; Jan Schmidt

    2004-01-01

    AIM: There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU).Therefore the objective of this study was to determine the combined effects of adenovirus-mediated wild-type (wt) p53gene transfer and 5-FU chemotherapy on pancreatic cancer cells with different p53 gene status.METHODS: Human pancreatic cancer cell lines Capan-1p53mut,Capan-2p53wt, FAMPACp53mut, PANC1p53mut, and rat pancreatic cancer cell lines ASp53wt and DSL6Ap53null were used for in vitro studies. Following infection with different ratios of Adp53-particles (MOI) in combination with 5-FU, proliferation of tumor cells and apoptosis were quantified by cell proliferation assay (WST-1) and FACS (PI-staining). In addition, DSL6A syngeneic pancreatic tumor cells were inoculated subcutaneously in to Lewis rats for in vivo studies.Tumor size, apoptosis (TUNEL) and survival were determined.RESULTS: Ad-p53 gene transfer combined with 5-FU significantly inhibited tumor cell proliferation and substantially enhanced apoptosis in all four cell lines with an alteration in the p53 gene compared to those two cell lines containing wt-p53. In vivo experiments showed the most effective tumor regression in animals treated with Ad-p53 plus 5-FU. Both in vitro and in vivo analyses revealed that a sublethal dose of Ad-p53 augmented the apoptotic response induced by 5-FU.CONCLUSION: Our results suggest that Ad-p53 may synergistically enhance 5-FU-chemosensitivity most strikingly in pancreatic cancer cells lacking p53 function. These findings illustrate that the anticancer efficacy of this combination treatment is dependent on the p53 gene status of the target tumor cells.

  8. Evaluation of chromium, nickel, iron and manganese content in wheat, flour, bran and selected baked products

    Directory of Open Access Journals (Sweden)

    Bawiec Piotr

    2014-06-01

    Full Text Available Considering the nutritional values, breadstuff plays a big part in covering human nourishment needs and constitutes a base of all day diet. Moreover, bread is an excellent source of numerous vitamins and minerals the abundance of which depends on the degree of grinding. Thus, it seems to be very important to know the composition and level of bio-elements. That is why the main target of this study was to evaluate the concentration of selected trace elements: chromium (Cr, nickel (Ni, iron (Fe and manganese (Mn in wheat grain, wheat bran, different wheat and rye flour types and variety of breadstuff also with addition of grains and seeds from different bakeries and mills. Another task was to analyze if the technological process has an influence on secondary despoil of bread goods with heavy metal elements. The analyzed trace elements were measured with a precise and accurate atomic absorption spectrophotometric method (AAS and the results were expressed in mg/kg of selected sample. Obtained results show that bread and grain products are a good source of trace elements like chromium, nickel, iron and manganese. However, the higher levels of chromium and nickel in bread goods could rather be an effect of impurity caused by a technological process in mill and bakeries.

  9. Selenium protection from cadmium and chromium poisoning

    International Nuclear Information System (INIS)

    The interaction of selenium with cadmium and chromium was studied in 168 chicken-broilers (DWCxWR) divided into four equal groups. Eight-week old control animals received an intravenous dose of /sup 115m/Cd Chloride 370 KBq/Kg (Group I), or 51Cr Chloride 370 KBq/Kg (Group II). The kinetics of these isotopes were studied by scintillation spectrometry (NaI/TI) carried out for whole blood, plasma, plasma proteins, urine, feces and homogenates of all organs at various time intervals. Animals in Groups III and IV received eight subcutaneous doses of sodium selenate (5ug) at 8-week intervals prior to /sup 115m/Cd or 51Cr. The kinetics of these elements were studied as in the previous two groups. It was found that selenium affected those kinetics in two ways: (a) by increasing the excretion of Cd by 11 +/- 3% (P < 0.001) and that of Cr by 7 +/- 1% (P < 0.001); and (b) by favoring redistribution of those elements, with significant (P < 0.001) reductions in liver, endocrine glands and kidney and increases (P < 0.01) in bone. The study suggests that selenium protects the animals' vital organs from environmental pollutants, such as cadmium and chromium

  10. Identification, clonong and characterization of the p53 induced gene human wig-1

    OpenAIRE

    Hellborg, Fredrik

    2004-01-01

    The tumor suppressor p53 is a transcription factor that responds to various kinds of cellular stress. In respons to the sensed stress it is able to induces cell cycle arrest and apoptosis. In order to achieve these effects it transactivates target genes. Thus knowledge about p53 target genes and their function is vital for the understandnig of this important tumor suppressor. We previously identified a novel p53-induced mouse gene, wig-1, that encodes a 290 amino acid zin...

  11. Psychoneuroimmunology and natural killer cells: the chromium release whole blood assay.

    Science.gov (United States)

    Fletcher, Mary Ann; Barnes, Zachary; Broderick, Gordon; Klimas, Nancy G

    2012-01-01

    Natural killer (NK) cells are an essential component of innate immunity. These lymphocytes are also sensitive barometers of the effects of endogenous and exogenous stressors on the immune system. This chapter will describe a chromium ((51)Cr) release bioassay designed to measure the target cell killing capacity of NK cells (NKCC). Key features of the cytotoxicity assay are that it is done with whole blood and that numbers of effector cells are determined for each sample by flow cytometry and lymphocyte count. Effector cells are defined as CD3-CD56+ lymphocytes. Target cells are the K562 eyrthroleukemia cell line. Killing capacity is defined as number of target cells killed per effector cell, at an effector cell/target cell ratio of 1:1 during a 4 h in vitro assay.

  12. p53 acetylation enhances Taxol-induced apoptosis in human cancer cells.

    Science.gov (United States)

    Kim, Jae Hyeong; Yoon, Eun-Kyung; Chung, Hye-Jin; Park, Seong-Yeol; Hong, Kyeong-Man; Lee, Chang-Hun; Lee, Yeon-Su; Choi, Kyungho; Yang, Young; Kim, Kyungtae; Kim, In-Hoo

    2013-01-01

    Microtubule inhibitors (MTIs) such as Taxol have been used for treating various malignant tumors. Although MTIs have been known to induce cell death through mitotic arrest, other mechanisms can operate in MTI-induced cell death. Especially, the role of p53 in this process has been controversial for a long time. Here we investigated the function of p53 in Taxol-induced apoptosis using p53 wild type and p53 null cancer cell lines. p53 was upregulated upon Taxol treatment in p53 wild type cells and deletion of p53 diminished Taxol-induced apoptosis. p53 target proteins including MDM2, p21, BAX, and β-isoform of PUMA were also upregulated by Taxol in p53 wild type cells. Conversely, when the wild type p53 was re-introduced into two different p53 null cancer cell lines, Taxol-induced apoptosis was enhanced. Among post-translational modifications that affect p53 stability and function, p53 acetylation, rather than phosphorylation, increased significantly in Taxol-treated cells. When acetylation was enhanced by anti-Sirt1 siRNA or an HDAC inhibitor, Taxol-induced apoptosis was enhanced, which was not observed in p53 null cells. When an acetylation-defective mutant of p53 was re-introduced to p53 null cells, apoptosis was partially reduced compared to the re-introduction of the wild type p53. Thus, p53 plays a pro-apoptotic role in Taxol-induced apoptosis and acetylation of p53 contributes to this pro-apoptotic function in response to Taxol in several human cancer cell lines, suggesting that enhancing acetylation of p53 could have potential implication for increasing the sensitivity of cancer cells to Taxol.

  13. Gene expression profiles resulting from stable loss of p53 mirrors its role in tissue differentiation.

    Directory of Open Access Journals (Sweden)

    Oliver Couture

    Full Text Available The tumor suppressor gene p53 is involved in a variety of cellular activities such as cellular stress responses, cell cycle regulation and differentiation. In our previous studies we have shown p53's transcription activating role to be important in osteoblast differentiation. There is still a debate in the literature as to whether p53 inhibits or promotes differentiation. We have found p53 heterozygous mice to show a p53 dependency on some bone marker gene expression that is absent in knockout mice. Mice heterozygous for p53 also show a higher incidence of osteosarcomas than p53 knockout mice. This suggests that p53 is able to modify the environment within osteoblasts. In this study we compare changes in gene expression resulting after either a transient or stable reduction in p53. Accordingly we reduced p53 levels transiently and stably in C2C12 cells, which are capable of both myoblast and osteoblast differentiation, and compared the changes in gene expression of candidate genes regulated by the p53 pathway. Using a PCR array to assay for p53 target genes, we have found different expression profiles when comparing stable versus transient knockdown of p53. As expected, several genes with profound changes after transient p53 loss were related to apoptosis and cell cycle regulation. In contrast, stable p53 loss produced a greater change in MyoD and other transcription factors with tissue specific roles, suggesting that long term loss of p53 affects tissue homeostasis to a greater degree than changes resulting from acute loss of p53. These differences in gene expression were validated by measuring promoter activity of different pathway specific genes involved in differentiation. These studies suggest that an important role for p53 is context dependent, with a stable reduction in p53 expression affecting normal tissue physiology more than acute loss of p53.

  14. Standard Specification for Pressure Consolidated Powder Metallurgy Iron-Nickel-Chromium-Molybdenum (UNS N08367), Nickel-Chromium-Molybdenum-Columbium (Nb) (UNS N06625), Nickel-Chromium-Iron Alloys (UNS N06600 and N06690), and Nickel-Chromium-Iron-Columbium-Molybdenum (UNS N07718) Alloy Pipe Flanges, Fittings, Valves, and Parts

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2015-01-01

    Standard Specification for Pressure Consolidated Powder Metallurgy Iron-Nickel-Chromium-Molybdenum (UNS N08367), Nickel-Chromium-Molybdenum-Columbium (Nb) (UNS N06625), Nickel-Chromium-Iron Alloys (UNS N06600 and N06690), and Nickel-Chromium-Iron-Columbium-Molybdenum (UNS N07718) Alloy Pipe Flanges, Fittings, Valves, and Parts

  15. 75 FR 65067 - National Emission Standards for Hazardous Air Pollutant Emissions: Hard and Decorative Chromium...

    Science.gov (United States)

    2010-10-21

    ... Decorative Chromium Electroplating and Chromium Anodizing Tanks; Group I Polymers and Resins; Marine Tank...: Hard and Decorative Chromium Electroplating and Chromium Anodizing Tanks; Group I Polymers and Resins... Tanks. Group I Polymers and Resins Production.. Scott Throwe, (202) 564-7013,...

  16. Alpha-emitting isotopes and chromium in a coastal California aquifer

    Science.gov (United States)

    Densmore, Jill N.; Izbicki, John A.; Murtaugh, Joseph M.; Swarzenski, Peter W.; Bullen, Thomas D.

    2014-01-01

    The unadjusted 72-h gross alpha activities in water from two wells completed in marine and alluvial deposits in a coastal southern California aquifer 40 km north of San Diego were 15 and 25 picoCuries per liter (pCi/L). Although activities were below the Maximum Contaminant Level (MCL) of 15 pCi/L, when adjusted for uranium activity; there is concern that new wells in the area may exceed MCLs, or that future regulations may limit water use from the wells. Coupled well-bore flow and depth-dependent water-quality data collected from the wells in 2011 (with analyses for isotopes within the uranium, actinium, and thorium decay-chains) show gross alpha activity in marine deposits is associated with decay of naturally-occurring 238U and its daughter 234U. Radon activities in marine deposits were as high as 2230 pCi/L. In contrast, gross alpha activities in overlying alluvium within the Piedra de Lumbre watershed, eroded from the nearby San Onofre Hills, were associated with decay of 232Th, including its daughter 224Ra. Radon activities in alluvium from Piedra de Lumbre of 450 pCi/L were lower than in marine deposits. Chromium VI concentrations in marine deposits were less than the California MCL of 10 μg/L (effective July 1, 2014) but δ53Cr compositions were near zero and within reported ranges for anthropogenic chromium. Alluvial deposits from the nearby Las Flores watershed, which drains a larger area having diverse geology, has low alpha activities and chromium as a result of geologic and geochemical conditions and may be more promising for future water-supply development.

  17. Chromium-induced membrane damage: protective role of ascorbic acid

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Importance of chromium as environmental toxicant is largely due to impact on the body to produce cellular toxicity. The impact of chromium and their supplementation with ascorbic acid was studied on plasma membrane of liver and kidney in male Wistar rats (80 - 100gbody weight). It has been observed that the intoxication with chromium ( i. p. ) at the dose of 0.8 mg/100g body weight per day for a period of 28 days causes significant increase in the level of cholesterol and decrease in the level of phospbolipid of both liver and kidney. The alkaline pbosphatase, total ATPase and Na + -K + -ATPase activities were significantly decreased in both liver and kidney after chromium treatment,except total ATPase activity of kidney. It is suggested that chromium exposure at the present dose and duration induce for the alterations of structure and function of both liver and kidney plasma membrane. Ascorbic acid ( i.p. at the dose of 0.5 mg,/100g body weight per day for period of 28 days) supplementation can reduce these structural changes in the plasma membrane of liver and kidney. But the functional changes can not be completely replenished by the ascorbic acid supplementation in response to chromium exposure. So it is also suggested that ascorbic acid (nutritional antioxidant) is useful free radical scavenger to restrain the chromium-induced membrane damage.

  18. Bioavailability of a potato chromium complex to the laboratory rat

    International Nuclear Information System (INIS)

    Research objectives were to study the effect of food source, preparation method and chemical form on bioavailability of chromium. Chromium concentration in potatoes was determined and tubers labeled either intrinsically or extrinsically with radioactive chromate. A labeled chromium complexes was isolated from preparations of raw, baked or fried potatoes and chromatographed on gel permeation media. Availability of the potato chromium complex to the rat was examined in three feeding studies. Animals were dosed with radioactive extrinsically or intrinsically labeled potato extract or with chromate. A labeled chromium complex was isolated from gastrointestinal contents of rats and chromatographed. Potato pulp and peel contained 1.63 and 2.70 μg Cr/g tissue respectively. True and apparent absorption from extrinsically labeled feedings were 33.4 +/- 4.7 and 29.8 +/- 11.2% respectively, and no differences existed between absorption from raw and cooked potatoes. Absorption from the extrinsic labeled potatoes differed significantly from absorption of inorganic chromatium. Apparent absorption of raw (11.1 +/- 7.9%) and cooked (-0.7 +/- 2.8%) intrinsically labeled feedings differed significantly. Absorption of inorganic chromium was 17.8% (true) and 11.5% (apparent). Examination of the chromium complex isolated from gastrointestinal tract contents showed enlargement of the complex in the stomach after consumption

  19. Stabilization of chromium salt in ordinary portland cement

    Indian Academy of Sciences (India)

    Damir Barbir; Pero Dabić; Petar Krolo

    2012-12-01

    Ordinary Portland cement (OPC) samples containing the chromium salt have been investigated using differential microcalorimetry, conductometry and Fourier transform infrared spectroscopic analysis. The effect of chromium on OPC hydration was evaluated by continuous observing of early hydration. The microcalorimetrical results show that with increasing the share of chromium salt, heat maximums assume lower values and the occurrence of the maximum registered in the earlier hydration times. Conductometrical measurements show that with increasing addition of chromium salt, curve did not show any specific shape, immediate drop in specific conductivity is noticed and the maximum is reached earlier. This coincides with microcalorimetrical results. It can be concluded that the addition of chromium does not affect the mechanism of the hydration process, but it does affect the kinetic parameters and dynamics of the cement hydration process. It was found that chromium salt addition to the cement–water system is acceptable up to 2 wt.%. According to standard EN 196-3 for OPC, the beginning of binding time should occur after 60 minutes. Increased amount of chromium over 2 wt.% significantly accelerate the beginning of binding time and for the system it is not acceptable.

  20. Chromium speciation in rainwater: temporal variability and atmospheric deposition

    Energy Technology Data Exchange (ETDEWEB)

    Kieber, R.J.; Willey, J.D.; Zvalaren, S.D. [University of North Carolina at Wilmington, Wilmington, NC (United States). Dept. of Chemistry

    2002-12-15

    Chromium is released into the atmosphere by a variety of anthropogenic activities which include steel manufacturing, leather tanning, wood presentation and fossil fuel combustion. The concentrations of the various chromium species were determined in 89 rainwater samples collected in Wilmington, NC from October 1, 1999 to December 31, 2001. Volume weighted annual average concentrations of Cr{sub total}, particulate Cr, Cr(III)(aq), and Cr(VI)(aq) were 4.6, 2.2, 0.8 and 1.2 nM, respectively. There was distinct seasonal and diurnal variability in the concentrations of the various chromium species. Chromium emissions to the global atmosphere by both natural and anthropogenic sources are estimated to be 2.2 x 10{sup 9} mol/yr. Using rainwater concentration data along with other published rainwater Cr concentrations and an estimate for total global annual rain, the total global flux of chromium removed from the atmosphere via wet deposition is 2.1 x 10{sup 9} mol/yr. This represents complete removal of Cr and indicates that essentially all chromium released into the global atmosphere is removed via rain. About half this chromium is dissolved with roughly equal concentrations of toxic Cr(VI) and relatively harmless Cr(III) species. 48 refs., 4 figs., 3 tabs.

  1. Workshop on effects of chromium coating on Nb3Sn superconductor strand: Proceedings

    International Nuclear Information System (INIS)

    This report discusses the following topics: Chromium coating on superconductor strand -- an overview; technology of chromium plating; comparison of wires plated by different platers; search for chromium in copper; strand manufactures' presentations; chromium plating at the Lawrence Livermore National Laboratory; a first look at a chromium plating process development project tailored for T.P.X. and I.T.E.R. strand; and influence of chromium diffusion and related phenomena on the reference ratios of bare and chromium plated Nb3Sn strand

  2. Workshop on effects of chromium coating on Nb{sub 3}Sn superconductor strand: Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    1994-04-12

    This report discusses the following topics: Chromium coating on superconductor strand -- an overview; technology of chromium plating; comparison of wires plated by different platers; search for chromium in copper; strand manufactures` presentations; chromium plating at the Lawrence Livermore National Laboratory; a first look at a chromium plating process development project tailored for T.P.X. and I.T.E.R. strand; and influence of chromium diffusion and related phenomena on the reference ratios of bare and chromium plated Nb{sub 3}Sn strand.

  3. Detection of highly toxic elements (lead and chromium) in commercially available eyeliner (kohl) using laser induced break down spectroscopy

    Science.gov (United States)

    Gondal, M. A.; Dastageer, M. A.; Al-Adel, F. F.; Naqvi, A. A.; Habibullah, Y. B.

    2015-12-01

    A sensitive laser induced breakdown spectroscopic system was developed and optimized for using it as a sensor for the detection of trace levels of lead and chromium present in the cosmetic eyeliner (kohl) of different price ranges (brands) available in the local market. Kohl is widely used in developing countries for babies as well adults for beautification as well eyes protection. The atomic transition lines at 405.7 nm and 425.4 nm were used as the marker lines for the detection of lead and chromium respectively. The detection system was optimized by finding the appropriate gate delay between the laser excitation and the data acquisition system and also by achieving optically thin plasma near the target by establishing the local thermodynamic equilibrium condition. The detection system was calibrated for these two hazardous elements and the kohl samples under investigation showed 8-15 ppm by mass of lead and 4-9 ppm by mass of Chromium, which are higher than the safe permissible levels of these elements. The limits of detection of the LIBS system for lead and chromium were found to be 1 and 2 ppm respectively.

  4. Fertilizers and Mixed Crop Cultivation of Chromium Tolerant and Sensitive Plants under Chromium Toxicity

    OpenAIRE

    B. Dheeba; Sampathkumar, P; Kannan, K.

    2015-01-01

    Zea mays (maize) and Vigna radiata (green gram) are found to be the chromium (Cr) tolerant and sensitive plants, respectively. In the present paper, we investigate the reduction of the toxicity of Cr in the sensitive plants by the mixed crop cultivation in the field using various amendments. Further, the potassium dichromate was used as the source of hexavalent Cr. The results indicated that Cr adversely affects both the growth and yield of plants. The soil properties vary with Cr and differe...

  5. Microbial Diversity of Chromium-Contaminated Soils and Characterization of Six Chromium-Removing Bacteria

    Science.gov (United States)

    He, Zhiguo; Hu, Yuting; Yin, Zhen; Hu, Yuehua; Zhong, Hui

    2016-06-01

    Three soil samples obtained from different sites adjacent to a chromium slag heap in a steel alloy factory were taken to examine the effect of chromium contamination on soil bacterial diversity as determined by construction of 16S rDNA clone libraries and sequencing of selected clones based on restriction fragment length polymorphism (RFLP) analysis. Results revealed that Betaproteobacteria, Gammaproteobacteria, Firmicutes, and Alphaproteobacteria occurred in all three soil samples, although the three samples differed in their total diversity. Sample 1 had the highest microbial diversity covering 12 different classes, while Sample 3 had the lowest microbial diversity. Strains of six different species were successfully isolated, one of which was identified as Zobellella denitrificans. To our knowledge, this is the first report of a strain belonging to the genus Zobellella able to resist and reduce chromium. Among all isolates studied, Bacillus odysseyi YH2 exhibited the highest Cr(VI)-reducing capability, with a total removal of 23.5 % of an initial Cr(VI) concentration of 350 mg L-1.

  6. A REVIEW OF BIOSORPTION OF CHROMIUM IONS BY MICROORGANISMS

    Directory of Open Access Journals (Sweden)

    Inga Zinicovscaia

    2012-12-01

    Full Text Available Due to its widespread industrial use, chromium has become a serious pollutant in diverse environmental settings. The main source of chromium pollution including the Republic o Moldova is industry. It is a great need to develop new eco-friendly methods of chromium removal. Biosorption of heavy metals is a most promising technology involved in the removal of toxic metals from industrial waste streams and natural waters. This article is an extended abstract of a communication presented at the Conference Ecological Chemistry 2012

  7. Both p53-PUMA/NOXA-Bax-mitochondrion and p53-p21cip1 pathways are involved in the CDglyTK-mediated tumor cell suppression

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Zhendong, E-mail: zdyu@hotmail.com [Department of Clinical laboratory, Peking University Shenzhen Hospital, Guangdong (China); Wang, Hao [Department of pathology, The Chinese University of Hong Kong, Hong Kong (China); Zhang, Libin; Tang, Aifa; Zhai, Qinna; Wen, Jianxiang; Yao, Li [Department of Clinical laboratory, Peking University Shenzhen Hospital, Guangdong (China); Li, Pengfei, E-mail: lipengfei@cuhk.edu.hk [Department of pathology, The Chinese University of Hong Kong, Hong Kong (China)

    2009-09-04

    CDglyTK fusion suicide gene has been well characterized to effectively kill tumor cells. However, the exact mechanism and downstream target genes are not fully understood. In our study, we found that CDglyTK/prodrug treatment works more efficiently in p53 wild-type (HONE1) cells than in p53 mutant (CNE1) cells. We then used adenovirus-mediated gene delivery system to either knockdown or overexpress p53 and its target genes in these cells. Consistent results showed that both p53-PUMA/NOXA/Bcl2-Bax and p53-p21 pathways contribute to the CDglyTK induced tumor cell suppression. Our work for the first time addressed the role of p53 related genes in the CDglyTK/prodrug system.

  8. Both p53-PUMA/NOXA-Bax-mitochondrion and p53-p21cip1 pathways are involved in the CDglyTK-mediated tumor cell suppression

    International Nuclear Information System (INIS)

    CDglyTK fusion suicide gene has been well characterized to effectively kill tumor cells. However, the exact mechanism and downstream target genes are not fully understood. In our study, we found that CDglyTK/prodrug treatment works more efficiently in p53 wild-type (HONE1) cells than in p53 mutant (CNE1) cells. We then used adenovirus-mediated gene delivery system to either knockdown or overexpress p53 and its target genes in these cells. Consistent results showed that both p53-PUMA/NOXA/Bcl2-Bax and p53-p21 pathways contribute to the CDglyTK induced tumor cell suppression. Our work for the first time addressed the role of p53 related genes in the CDglyTK/prodrug system.

  9. Effect of p53 genotype on gene expression profiles in murine liver

    International Nuclear Information System (INIS)

    The tumor suppressor protein p53 is a key regulatory element in the cell and is regarded as the 'guardian of the genome'. Much of the present knowledge of p53 function has come from studies of transgenic mice in which the p53 gene has undergone a targeted deletion. In order to provide additional insight into the impact on the cellular regulatory networks associated with the loss of this gene, microarray technology was utilized to assess gene expression in tissues from both the p53-/- and p53+/- mice. Six male mice from each genotype (p53+/+, p53+/-, and p53-/-) were humanely killed and the tissues processed for microarray analysis. The initial studies have been performed in the liver for which the Dunnett test revealed 1406 genes to be differentially expressed between p53+/+ and p53+/- or between p53+/+ and p53-/- at the level of p ≤ 0.05. Both genes with increased expression and decreased expression were identified in p53+/- and in p53-/- mice. Most notable in the gene list derived from the p53+/- mice was the significant reduction in p53 mRNA. In the p53-/- mice, not only was there reduced expression of the p53 genes on the array, but genes associated with DNA repair, apoptosis, and cell proliferation were differentially expressed, as expected. However, altered expression was noted for many genes in the Cdc42-GTPase pathways that influence cell proliferation. This may indicate that alternate pathways are brought into play in the unperturbed liver when loss or reduction in p53 levels occurs

  10. The inherent instability of mutant p53 is alleviated by Mdm2 or p16INK4a loss

    OpenAIRE

    Terzian, Tamara; Suh, Young-Ah; Iwakuma, Tomoo; Post, Sean M.; Neumann, Manja; Lang, Gene A.; Van Pelt, Carolyn S.; Lozano, Guillermina

    2008-01-01

    The p53 tumor suppressor is often disrupted in human cancers by the acquisition of missense mutations. We generated mice with a missense mutation at codon 172 that mimics the p53R175H hot spot mutation in human cancer. p53 homozygous mutant mice have unstable mutant p53 in normal cells and stabilize mutant p53 in some but not all tumors. To investigate the significance of these data, we examined the regulation of mutant p53 stability by Mdm2, an E3 ubiquitin ligase that targets p53 for degrad...

  11. Thermal incorporation behavior during the reduction and stabilization of chromium wastes

    OpenAIRE

    Yang, Jun; 楊駿

    2015-01-01

    The possibility of employing periclase to stabilize chromium in chromium wastes into spinel-based ceramics through thermal method was investigated by heating mixture of simulated chromium waste and magnesium oxide. Different types of magnesium oxide precursors were introduced to incorporate chromium oxide into magnesiochromite (MgCr2O4) ranging from 550 ºC to 1350 ºC. Magnesium oxide precursors of both types can effectively incorporate chromium oxide but via different mechanisms. Three main f...

  12. Effects of Supplemental Dietary Chromium on Yield and Nutrient Digestibility of Laying Hens Under Low Temperature

    OpenAIRE

    ŞAHİN, Kazım; ERTAŞ, O. Nihat; GÜLER, Talat; ÇİFTÇİ, Mehmet

    2001-01-01

    This study was conducted to determine the effects of chromium picolinate (CrPi) added into diet containing 710.3 ppb chromium on yield and nutrient digestibility of laying hens at low temperature. Forty-six-week-old laying hens were randomly assigned to four groups of 30 hens per group. Treatment groups were fed different supplemental dietary chromium levels. Thus, hens were fed diets with no supplemental chromium (Control Group), 100 ppb of supplemental chromium (100 Group), 200 ppb of s...

  13. Evaluation of chromium in red blood cells as an indicator of exposure to hexavalent chromium: An in vitro study.

    Science.gov (United States)

    Devoy, Jérôme; Géhin, Antoine; Müller, Samuel; Melczer, Mathieu; Remy, Aurélie; Antoine, Guillaume; Sponne, Isabelle

    2016-07-25

    Chromium(VI) compounds are classified as carcinogenic to humans. Whereas chromium measurements in urine and whole blood (i.e., including plasma) are indicative of recent exposure, chromium in red blood cells (RBC) is attributable specifically to Cr(VI) exposure. Before recommending Cr in RBC as a biological indicator of Cr(VI) exposure, in-vitro studies must be undertaken to assess its reliability. The present study examines the relationship between the chromium added to a blood sample and that subsequently found in the RBC. After incubation of total blood with chromium, RBC were isolated, counted and their viability assessed. Direct analysis of chromium in RBC was conducted using Atomic Absorption Spectrometry. Hexavalent, but not trivalent Cr, was seen to accumulate in the RBC and we found a strong correlation between the Cr(VI) concentration added to a blood sample and the amount of Cr in RBC. This relationship appears to be independent of the chemical properties of the human blood samples (e.g., different blood donors or different reducing capacities). Even though in-vivo studies are still needed to integrate our understanding of Cr(VI) toxicokinetics, our findings reinforce the idea that a single determination of the chromium concentration in RBC would enable biomonitoring of critical cases of Cr(VI) exposure. PMID:27178267

  14. Chromium accumulation, microorganism population and enzyme activities in soils around chromium-containing slag heap of steel alloy factory

    Institute of Scientific and Technical Information of China (English)

    HUANG Shun-hong; PENG Bing; YANG Zhi-hui; CHAI Li-yuan; ZHOU Li-cheng

    2009-01-01

    The environmental risk of chromium pollution is pronounced in soils adjacent to chromate industry. It is important to investigate the functioning of soil microorganisms in ecosystems exposed to long-term contamination by chromium. 45 soil samples obtained from different places of the slag heap in a steel alloy factory were analyzed for chromium contamination level and its effect on soil microorganisms and enzyme activities. The results show that the average concentrations of total Cr in the soil under the slag heap, adjacent to the slag heap and outside the factory exceed the threshold of Secondary Environmental Quality Standard for Soil in China by 354%, 540% and 184%, respectively, and are 15, 21 and 9 times higher than the local background value, respectively. Elevated chromium loadings result in changes in the activity of the soil microbe, as indicated by the negative correlations between soil microbial population and chromium contents. Dehydrogenase activity is greatly depressed by chromium in the soil. The results imply that dehydrogenase activity can be used as an indicator for the chromium pollution level in the area of the steel alloy factory.

  15. Oxazoloisoindolinones with in vitro antitumor activity selectively activate a p53-pathway through potential inhibition of the p53-MDM2 interaction.

    Science.gov (United States)

    Soares, Joana; Pereira, Nuno A L; Monteiro, Ângelo; Leão, Mariana; Bessa, Cláudia; Dos Santos, Daniel J V A; Raimundo, Liliana; Queiroz, Glória; Bisio, Alessandra; Inga, Alberto; Pereira, Clara; Santos, Maria M M; Saraiva, Lucília

    2015-01-23

    One of the most appealing targets for anticancer treatment is the p53 tumor suppressor protein. In half of human cancers, this protein is inactivated due to endogenous negative regulators such as MDM2. Actually, restoring the p53 activity, particularly through the inhibition of its interaction with MDM2, is considered a valuable therapeutic strategy against cancers with a wild-type p53 status. In this work, we report the synthesis of nine enantiopure phenylalaninol-derived oxazolopyrrolidone lactams and the evaluation of their biological effects as p53-MDM2 interaction inhibitors. Using a yeast-based screening assay, two oxazoloisoindolinones, compounds 1b and 3a, were identified as potential p53-MDM2 interaction inhibitors. The molecular mechanism of oxazoloisoindolinone 3a was further validated in human colon adenocarcinoma HCT116 cells with wild-type p53 (HCT116 p53(+/+)) and in its isogenic derivative without p53 (HCT116 p53(-/-)). Indeed, using these cells, we demonstrated that oxazoloisoindolinone 3a exhibited a p53-dependent in vitro antitumor activity through induction of G0/G1-phase cell cycle arrest and apoptosis. The selective activation of a p53-apoptotic pathway by oxazoloisoindolinone 3a was further supported by the occurrence of PARP cleavage only in p53-expressing HCT116 cells. Moreover, oxazoloisoindolinone 3a led to p53 protein stabilization and to the up-regulation of p53 transcriptional activity with increased expression levels of several p53 target genes, as p21(WAF1/CIP1), MDM2, BAX and PUMA, in p53(+/+) but not in p53(-/-) HCT116 cells. Additionally, the ability of oxazoloisoindolinone 3a to block the p53-MDM2 interaction in HCT116 p53(+/+) cells was confirmed by co-immunoprecipitation. Finally, the molecular docking analysis of the interactions between the synthesized compounds and MDM2 revealed that oxazoloisoindolinone 3a binds to MDM2. Altogether, this work adds, for the first time, the oxazoloisoindolinone scaffold to the list of

  16. Interlaboratory comparison survey of the determination of chromium, manganese, iron, titanium in dust and arsenic, cadmium, cobalt and chromium in urine

    International Nuclear Information System (INIS)

    This report describes an intercomparison survey based on the Danish External Quality Assessment Scheme (DEQAS). The study was carried out in 1998 for 10 laboratories in a research project on assessment of levels and health effects of airborne particulate matter in mining, metal refining and metal working industries using nuclear and related analytical techniques. The project was co-ordinated by the IAEA. Eight laboratories measured chromium (Cr), manganese (Mn), iron (Fe) and titanium (Ti) in welding fume dust loaded on filters. Six laboratories measured arsenic (As), four laboratories measured cadmium (Cd), five laboratories measured cobalt (Co) and four laboratories measured chromium (Cr) in urine. The target values of the quality control materials were traceable to certified reference materials with respect to Cr in welding fume and As, Cd, Co and Cr in urine. For Mn, Fe and Ti in welding fume the target values were established based on values from reference laboratories and consensus values from several DEQAS rounds. For evaluating the analytical performance the z-score and En number were calculated as recommended in ISO 45. The judgement of laboratories according to the performance scores revealed that few laboratories could maintain an ideal z-score below 3 and an ideal En number below 1. Nearly all participants had a high precision in the reported results. This is a good basis for improvements. The deviations from the target values appear to be systematic, because the deviations for Mn, Fe, Ti in welding dust as well as for As, Cd, Co and Cr in urine were a linear function of the target values (ISO 5725 evaluation). The cause for this bias is unknown at present and might not be the same for all participants. It is necessary to look further into the cause for this bias. Therefore, validation of the methodologies and regularly use of certified reference materials are highly recommended. (author)

  17. Effects of Chromium(VI) and Chromium(III) on Desulfovibrio vulgaris Cells

    Energy Technology Data Exchange (ETDEWEB)

    M.E. Clark; A. Klonowska; S.B. Thieman; B. Giles; J.D. Wall; and M.W. Fields

    2007-04-19

    Desulfovibrio vulgaris ATCC 29579 is a well studied sulfate reducer that has known capabilities of reducing heavy metals and radionuclides, like chromium and uranium. Cultures grown in a defined medium (i.e. LS4D) had a lag period of approximately 40 h when exposed to 50 μMof Cr(VI). Substrate analysis revealed that although chromium is reduced within the first 5 h, growth does not resume for another 35 h. During this time, small amounts of lactate are still utilized but the reduction of sulfate does not occur. Sulfate reduction occurs concurrently with the accumulation of acetate approximately 40 h after inoculation, when growth resumes. Similar amounts of hydrogen are produced during this time compared to hydrogen production by cells not exposed to Cr(VI); therefore an accumulation of hydrogen cannot account for the utilization of lactate. There is a significant decrease in the carbohydrate to protein ratio at approximately 25 h, and this result indicated that lactate is not converted to glycogen. Most probable number analysis indicated that cell viability decreased steadily after inoculation and reached approximately 6 x 104 cells/ml 20 h post-chromium exposure. Regeneration of reducing conditions during chromium exposure does not induce growth and in fact may make the growth conditions even more unfavorable. This result suggested that an increase in Eh was not solely responsible for the decline in viability. Cell pellets collected 10 h after chromium-exposure were unable to resume growth when suspended into fresh medium. Supernatants from these pellets were able to support cell growth upon re- inoculation. D. vulgaris cells treated with a non-dose dependent addition of ascorbate at the same time of Cr(VI) addition did not enter a lag period. Ascorbate added 3 h post-Cr(VI) exposure did not prevent the growth lag. These results indicated that Desulfovibrio utilized lactate to reduce Cr(VI) without the reduction of sulfate, that the decline in cell viability and

  18. Scientific Opinion on ChromoPrecise® cellular bound chromium yeast added for nutritional purposes as a source of chromium in food supplements and the bioavailability of chromium from this source

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS

    2012-11-01

    Full Text Available The Panel on Food Additives and Nutrient Sources added to Food (ANS provides a scientific opinion re-evaluating the safety of ChromoPrecise® cellular bound chromium yeast added for nutritional purposes as a source of chromium in food supplements and the bioavailability of chromium from this source. ChromoPrecise® is a yeast preparation with an enriched trivalent chromium content, obtained by culture of Saccharomyces cerevisiae in the presence of chromium chloride. A daily intake of 100 µg chromium(III. There are limited data on the nature and identity of the organic chromium(III compounds contained in chromium-enriched yeast and on their toxicokinetic and toxicodynamic behaviour in the body. Overall, the Panel concluded that the bioavailability in man of chromium from chromium-enriched yeast is potentially up to approximately ten times higher than that of chromium from chromium chloride. A NOAEL of 2500 mg/kg bw/day ChromoPrecise® was identified in a 90-day feeding study in rats; no evidence of adverse effects of chromium yeasts were reported in other animal studies investigating the effects of dietary supplementation with chromium yeast. ChromoPrecise® chromium yeast was non-genotoxic in a range of in vitro genotoxicity studies. Although no information was available on the chronic toxicity, carcinogenicity or reproductive toxicity of ChromoPrecise® chromium yeast, the ANS Panel has previously concluded that trivalent chromium is not carcinogenic, and limited data on other chromium yeasts provide no evidence of an effect on reproductive endpoints. No adverse effects have been reported in clinical efficacy trials with chromium yeasts. The Panel concluded that the use of ChromoPrecise® chromium yeast in food supplements is not of concern, despite the lack of data on the nature and identity of the organic chromium(III compounds contained in the product, provided that the intake does not exceed 250 μg/day, as recommended by the WHO.

  19. KSHV latent protein LANA2 inhibits sumo2 modification of p53

    Science.gov (United States)

    Laura, Marcos-Villar; de la Cruz-Herrera, Carlos F; Ferreirós, Alba; Baz-Martínez, Maite; Lang, Valerie; Vidal, Anxo; Muñoz-Fontela, Cesar; Rodríguez, Manuel S; Collado, Manuel; Rivas, Carmen

    2015-01-01

    Tumor suppressor p53 plays a crucial antiviral role and targeting of p53 by viral proteins is a common mechanism involved in virus oncogenesis. The activity of p53 is tightly regulated at the post-translational levels through a myriad of modifications. Among them, modification of p53 by SUMO has been associated with the onset of cellular senescence. Kaposi´s sarcoma-associated herpesvirus (KSHV) expresses several proteins targeting p53, including the latent protein LANA2 that regulates polyubiquitylation and phosphorylation of p53. Here we show that LANA2 also inhibits the modification of p53 by SUMO2. Furthermore, we show that the reduction of p53-SUMO2 conjugation by LANA2, as well as the p53-LANA2 interaction, both require the SUMOylation of the viral protein and its interaction with SUMO or SUMOylated proteins in a non-covalent manner. Finally, we show that the control of p53-SUMO2 conjugation by LANA2 correlates with its ability to inhibit SUMO2- and type I interferon-induced senescence. These results highlight the importance of p53 SUMOylation in the control of virus infection and suggest that viral oncoproteins could contribute to viral infection and cell transformation by abrogating p53 SUMOylation. PMID:25607652

  20. Influenza A Viruses Control Expression of Proviral Human p53 Isoforms p53β and Δ133p53α

    OpenAIRE

    Terrier, Olivier; Marcel, Virginie; Cartet, Gaëlle; Lane, David P; Lina, Bruno; Rosa-Calatrava, Manuel; Bourdon, Jean-Christophe

    2012-01-01

    Previous studies have described the role of p53 isoforms, including p53β and Δ133p53α, in the modulation of the activity of full-length p53, which regulates cell fate. In the context of influenza virus infection, an interplay between influenza viruses and p53 has been described, with p53 being involved in the antiviral response. However, the role of physiological p53 isoforms has never been explored in this context. Here, we demonstrate that p53 isoforms play a role in influenza A virus infec...

  1. CN Bimodality at Low Metallicity: The Globular Cluster M53

    CERN Document Server

    Martell, Sarah L; Briley, Michael M

    2007-01-01

    We present low resolution UV-blue spectroscopic observations of red giant stars in the globular cluster M53 ([Fe/H]=-1.84), obtained to study primordial abundance variations and deep mixing via the CN and CH absorption bands. The metallicity of M53 makes it an attractive target: a bimodal distribution of 3883 angstrom CN bandstrength is common in moderate- and high-metallicity globular clusters ([Fe/H] > -1.6) but unusual in those of lower metallicity ([Fe/H] < -2.0). We find that M53 is an intermediate case, and has a broad but not strongly bimodal distribution of CN bandstrength, with CN and CH bandstrengths anticorrelated in the less-evolved stars. Like many other globular clusters, M53 also exhibits a general decline in CH bandstrength and [C/Fe] abundance with rising luminosity on the red giant branch.

  2. Seawater and Chromium Isotopes - a Link to Atmospheric Weathering on Land?

    Science.gov (United States)

    Frei, R.; Poire, D.; Gaucher, C.

    2013-12-01

    The chromium (Cr) isotope system is currently being developed as a sensitive tracer to record redox fluctuations in seawater, via assessing, in first instance, the record contained in marine chemical sediments (carbonates, banded iron formations). Understanding of the cycling of Cr is vital in this respect, if the ultimate goal is to somehow establish a link between seawater signatures and processes which mobilize Cr from the continents into riverine systems, and finally into seawater. We have investigated the transport pathway of Cr in Misiones (Argentina), a subtropical region, where weathering of Cretaceous flood basalts of the Paraná province is extensive, leading to deep laterite weathering profiles, and where respective riverine catchments can be sampled and followed into the Paraná River and onwards until its delta in the Atlantic Ocean. The Rio Paraná with its tributaries creates a massive watershed that spreads throughout much of the south central part of the South American continent. The studied weathering profiles in the province of Misiones show up to 30% loss of chromium, accompanied by negatively fractionated (average (δ53Cr ~-0.35 ‰) weathering products (bulk soils), and this is compatible with the expected atmospheric oxidation of trivalent Cr(III) and mobilization of portions of the respective hexavalent Cr(VI) pool into the riverine systems. The isotopic composition of total Cr in the different catchments varies (δ53Cr = -0.23 to +0.31 ‰). Lowering of the isotope compositions is attributed to the extremely finely suspended load (isotopic composition of surface seawater potentially reflects the presence of oxidative weathering conditions on land. To which degree the isotopic composition can be related to the intensity of such weathering, and ultimately to atmospheric oxygen levels, is unclear and awaits further more detailed investigations. Our study emphasizes a great potential in the analyses of chemically precipitated sediments in the

  3. Contingency plans for chromium utilization. Publication NMAB-335

    International Nuclear Information System (INIS)

    The United States depends entirely on foreign sources for the critical material, chromium, making it very vulnerable to supply disruptions. This vulnerability results because chromium is essential for the fabrication of corrosion-resisting steels and high-temperature, oxidation-resisting alloys in applications that are vital to the nation's technological well-being; because no substitutes are known for these materials in those applications; and because the known, substantial deposits of chromite ore are only in a few geographical locations that could become inaccessible to the United States as a result of political actions. The effectiveness of programs such as stockpiling, conservation, and research and development for substitutes to reduce the impact of disruption of imports of chromite and ferrochromium are discussed. Alternatives for decreasing chromium consumption also are identified for chromium-containing materials in the areas of design, processing, and substitution

  4. Fabrication of high rate chromium getter sources for fusion applications

    International Nuclear Information System (INIS)

    Design and fabrication techniques are described for the manufacture of large-capacity chromium getter sources, analogous to the commercially available titanium getter source known as Ti-Ball, manufactured by Varian Associates

  5. IRIS Toxicological Review of Hexavalent Chromium (Peer Review Plan)

    Science.gov (United States)

    EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of hexavalent chromium that will appear on the Integrated Risk Information System (IRIS) database.

  6. Chromium and Polyphenols from Cinnamon and Insulin Sensitivity

    Science.gov (United States)

    Factors that improve insulin sensitivity usually lead to improvements in risk factors associated with the metabolic syndrome, diabetes, and cardiovascular diseases. Naturally occurring bioactive compounds that have been shown to improve insulin sensitivity include chromium and polyphenols found in ...

  7. The diffusion of chromium in a duplex alloy steel

    International Nuclear Information System (INIS)

    Diffusion of chromium in a duplex stainless steel containing approximately 8% ferrite has been investigated in the temperature range 600 to 10000C using the standard serial sectioning technique. The resulting concentration profiles exhibited up to four distinct regions. The two main regions are attributed to volume diffusion in the austenite and ferrite phases, the other zones being due to short circuiting paths. Volume diffusion in the austenite phase is in good agreement with chromium diffusion in Type 316 steel. The chromium diffusion coefficient in the ferrite phase of approximate composition 25 wt % Cr, 5 wt % Ni is given by: Dsub(α) = (6.0(+11,-3)) x 10-6 exp - ((212+-5)/RT) m2s-1 the activation energy being expressed in kJ.mol-1. Little evidence was found for enhanced chromium diffusion along austenite/ferrite interface boundaries. (author)

  8. Chromium isotope inventory of Cr(VI)-polluted groundwaters at four industrial sites in Central Europe

    Science.gov (United States)

    Novak, Martin; Martinkova, Eva; Chrastny, Vladislav; Stepanova, Marketa; Curik, Jan; Szurmanova, Zdenka; Cron, Marcel; Tylcer, Jiri; Sebek, Ondrej

    2016-04-01

    Chromium is one of the most toxic elements, especially in its dissolved Cr(VI) form. In the Czech Republic (Central Europe), massive contamination of groundwater has been reported at more than 200 industrial operations. Under suitable conditions, i.e., low Eh, and high availability of reductive agents, Cr(VI) in groundwater may be spontaneously reduced to solid, largely non-toxic Cr(III). This process is associated with a Cr isotope fractionation, with the residual liquid Cr(VI) becoming enriched in the heavier isotope 53Cr. At industrial operations that have been closed and/or where no further leakage of Cr(VI) occurs, the contaminated groundwater plume may be viewed as a closed system. At such sites, an increasing degree of Cr(VI) reduction should result in an increasing del53/52Cr value of the residual liquid. Here we present del53/52Cr systematics at four contaminated Czech sites, focusing on groundwaters. At two of the four sites (Zlate Hory, Loucna) we were also able to analyze the source of contamination. Chromium in the electroplating solutes was isotopically relatively light, with del53/52Cr values 4.0 per mil (mean of +1.7 per mil); at Letnany, del53/52Cr ranged between +2.0 and +4.5 per mil (mean of +3.2 per mil); and at Velesin, del53/52Cr ranged between +0.5 and +4.5 per mil (mean of +2.7 per mil). Cr(VI) reduction may proceed at Zlate Hory and Loucna, where del53/52Cr(VI) values in groundwater were on average higher than those of the contamination source. At these two sites, our Cr isotope data are not consistent with the existing estimates of the amount of dissolved and precipitated Cr: The pool size of solid Cr(III) in the soil was estimated at 6600 and 500 kg at Zlate Hory and Loucna, respectively. At the same time, the pool size of dissolved Cr(VI) was estimated at 50 and 1.2 kg at Zlate Hory and Loucna, respectively. It follows that, at both sites, less than 1 % of the entire Cr that had leaked into the aquifer an a liquid form remained in the

  9. p53 modulates the AMPK inhibitor compound C induced apoptosis in human skin cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Shi-Wei [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Wu, Chun-Ying [Division of Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wang, Yen-Ting [Department of Medical Research and Education, Cheng Hsin General Hospital, Taipei, Taiwan (China); Kao, Jun-Kai [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Department of Pediatrics, Children' s Hospital, Changhua Christian Hospital, Changhua, Taiwan (China); Lin, Chi-Chen; Chang, Chia-Che; Mu, Szu-Wei; Chen, Yu-Yu [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Chiu, Husan-Wen [Institute of Biotechnology, National Cheng-Kung University, Tainan, Taiwan (China); Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan (China); Chang, Chuan-Hsun [Department of Surgical Oncology, Cheng Hsin General Hospital, Taipei, Taiwan (China); Department of Nutrition Therapy, Cheng Hsin General Hospital, Taipei, Taiwan (China); School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan (China); Liang, Shu-Mei [Institute of Biotechnology, National Cheng-Kung University, Tainan, Taiwan (China); Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan (China); Chen, Yi-Ju [Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Huang, Jau-Ling [Department of Bioscience Technology, Chang Jung Christian University, Tainan, Taiwan (China); Shieh, Jeng-Jer, E-mail: shiehjj@vghtc.gov.tw [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan (China)

    2013-02-15

    Compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), has been reported to cause apoptotic cell death in myeloma, breast cancer cells and glioma cells. In this study, we have demonstrated that compound C not only induced autophagy in all tested skin cancer cell lines but also caused more apoptosis in p53 wildtype skin cancer cells than in p53-mutant skin cancer cells. Compound C can induce upregulation, phosphorylation and nuclear translocalization of the p53 protein and upregulate expression of p53 target genes in wildtype p53-expressing skin basal cell carcinoma (BCC) cells. The changes of p53 status were dependent on DNA damage which was caused by compound C induced reactive oxygen species (ROS) generation and associated with activated ataxia-telangiectasia mutated (ATM) protein. Using the wildtype p53-expressing BCC cells versus stable p53-knockdown BCC sublines, we present evidence that p53-knockdown cancer cells were much less sensitive to compound C treatment with significant G2/M cell cycle arrest and attenuated the compound C-induced apoptosis but not autophagy. The compound C induced G2/M arrest in p53-knockdown BCC cells was associated with the sustained inactive Tyr15 phosphor-Cdc2 expression. Overall, our results established that compound C-induced apoptosis in skin cancer cells was dependent on the cell's p53 status. - Highlights: ► Compound C caused more apoptosis in p53 wildtype than p53-mutant skin cancer cells. ► Compound C can upregulate p53 expression and induce p53 activation. ► Compound C induced p53 effects were dependent on ROS induced DNA damage pathway. ► p53-knockdown attenuated compound C-induced apoptosis but not autophagy. ► Compound C-induced apoptosis in skin cancer cells was dependent on p53 status.

  10. p53 modulates the AMPK inhibitor compound C induced apoptosis in human skin cancer cells

    International Nuclear Information System (INIS)

    Compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), has been reported to cause apoptotic cell death in myeloma, breast cancer cells and glioma cells. In this study, we have demonstrated that compound C not only induced autophagy in all tested skin cancer cell lines but also caused more apoptosis in p53 wildtype skin cancer cells than in p53-mutant skin cancer cells. Compound C can induce upregulation, phosphorylation and nuclear translocalization of the p53 protein and upregulate expression of p53 target genes in wildtype p53-expressing skin basal cell carcinoma (BCC) cells. The changes of p53 status were dependent on DNA damage which was caused by compound C induced reactive oxygen species (ROS) generation and associated with activated ataxia-telangiectasia mutated (ATM) protein. Using the wildtype p53-expressing BCC cells versus stable p53-knockdown BCC sublines, we present evidence that p53-knockdown cancer cells were much less sensitive to compound C treatment with significant G2/M cell cycle arrest and attenuated the compound C-induced apoptosis but not autophagy. The compound C induced G2/M arrest in p53-knockdown BCC cells was associated with the sustained inactive Tyr15 phosphor-Cdc2 expression. Overall, our results established that compound C-induced apoptosis in skin cancer cells was dependent on the cell's p53 status. - Highlights: ► Compound C caused more apoptosis in p53 wildtype than p53-mutant skin cancer cells. ► Compound C can upregulate p53 expression and induce p53 activation. ► Compound C induced p53 effects were dependent on ROS induced DNA damage pathway. ► p53-knockdown attenuated compound C-induced apoptosis but not autophagy. ► Compound C-induced apoptosis in skin cancer cells was dependent on p53 status

  11. Biosorption of Chromium (VI) from Aqueous Solutions onto Fungal Biomass

    OpenAIRE

    Ismael Acosta R.; Xöchitl Rodríguez; Conrado Gutiérrez; Ma. de Guadalupe Moctezuma

    2004-01-01

    The biosorption of chromium (VI) on eighteen different natural biosorbents: Natural sediment, chitosan, chitin, Aspergillus flavus I-V, Aspergillus fumigatus I-ll, Helmintosporium sp, Cladosporium sp, Mucor rouxii mutant, M. rouxii IM-80, Mucor sp-I and 2, Candida albicans and Cryptococcus neoformans was studied in this work. It was found that the biomass of C. neoformans, natural sediment, Helmintosporium sp and chitosan was more efficient to remove chromium (VI) (determined spectrophotometr...

  12. Stereology of carbide phase in modified hypereutectic chromium cast iron

    Directory of Open Access Journals (Sweden)

    J. Suchoń

    2010-04-01

    Full Text Available In paper are presented results of studies of carbide phase stereology modified hypereutectic wear resistance chromium cast iron which contains carbon about 3,5% and chromium about 25%. Three substances were applied to the modification: boron carbide (B4C, ferroniobium (FeNb and mixture of ferroniobium and rare-earth (RE. The measurements of geometrical features of carbides were conducted on microsection taken from castings wich were cooled with various velocities.

  13. Thermodynamic Equilibrium Diagrams of Sulphur-Chromium System

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The chemical and electrochemical equilibria in the presence of gaseous phase were investigated. Many substances, which consisted of sulphur and chromium, were considered. Various thermodynamic equilibria were calculated in different pressures. Calculation results were shown as log p―1/T and E―T diagrams. These diagrams may be used to study the corrosion of chromium in sulphur-containing circumstances. The diagrams are also used to thermodynami-cally determine the existence area of various substances and so on.

  14. Stereology of carbide phase in modified hypereutectic chromium cast iron

    OpenAIRE

    J. Suchoń; A. Studnicki; M. Przybył

    2010-01-01

    In paper are presented results of studies of carbide phase stereology modified hypereutectic wear resistance chromium cast iron which contains carbon about 3,5% and chromium about 25%. Three substances were applied to the modification: boron carbide (B4C), ferroniobium (FeNb) and mixture of ferroniobium and rare-earth (RE). The measurements of geometrical features of carbides were conducted on microsection taken from castings wich were cooled with various velocities.

  15. SCIENCE AND TECHNOLOGY ACTIVITIES FOR CHROMIUM IN THE 100 AREAS

    Energy Technology Data Exchange (ETDEWEB)

    PETERSEN SW

    2009-07-02

    {sm_bullet} Primary Objective: Protect the Columbia River - Focus is control and treatment of contamination at or near the shoreline, which is influenced by bank storage {sm_bullet} Secondary Objective: Reduce hexavalent chromium to <48 parts per billion (ppb) in aquifer (drinking water standard) - Large plumes with isolated areas of high chromium concentrations (> 40,000 ppb), - Unknown source location(s); probably originating in reactor operation areas

  16. Genetic Predisposition for Dermal Problems in Hexavalent Chromium Exposed Population

    OpenAIRE

    Priti Sharma; Vipin Bihari; Agarwal, Sudhir K.; Goel, Sudhir K.

    2012-01-01

    We studied the effect of genetic susceptibility on hexavalent chromium induced dermal adversities. The health status of population was examined from the areas of Kanpur (India) having the elevated hexavalent chromium levels in groundwater. Blood samples were collected for DNA isolation to conduct polymorphic determination of genes, namely: NQO1 (C609T), hOGG1 (C1245G), GSTT1, and GSTM1 (deletion). Symptomatic exposed subjects (n = 38) were compared with asymptomatic exposed subjects (n = 108)...

  17. Performance of chromium nitride based coatings under plastic processing conditions

    OpenAIRE

    Cunha, l.; Andritschky, M.; Pischow, K.; Wang, Z.(Institute of High Energy Physics, Beijing, China); Zarychta, A.; Miranda, A. S.; A.M. Cunha

    2000-01-01

    Chromium nitride based coatings were produced in the form of monolithic and multilayer coatings, by DC and RF reactive magnetron sputtering. These coatings were deposited onto stainless steel and tool steel substrates. Chromium nitride coatings have;proved to be wear and corrosion resistant. The combination of these characteristics was necessary to protect surfaces during plastic processing. In order to select the best coatings, some mechanical and tribological tests were performed. Har...

  18. DANGER OF HEXAVALENT CHROMIUM AND STRATEGY FOR THE REMEDITATION

    OpenAIRE

    Aniruddha Roy; Ayan Das; Nirmal Paul

    2013-01-01

    Some metals as micronutrients have a major role in the life and growth process of plants and animals. However, certain forms of some metals may also act as toxic material even in relatively small quantities. Chromium is such a metal, whose concentration above a certain limit may cause a serious problem to the health of living organisms. Chromium (Cr) may occur in several chemical forms in organic and inorganic systems. In biological systems only Cr (III) and Cr (VI) are signifi...

  19. Chromium reduction from slag on electromelting of stainless steel

    International Nuclear Information System (INIS)

    Specific features of chromium reduction from the slag on electromelting of stainless steel type Kh18N10T according to one- or two-slag procedure were studied. It was shown that one-slag melting technology allows double decrease of chromium losses in the form of incompletely reduced oxides. This occurs due to additional chemical reactions between metal and slag on their combined pouring into the ladle. 1 ref.; 3 figs

  20. Stability of p53 homologs.

    Directory of Open Access Journals (Sweden)

    Tobias Brandt

    Full Text Available Most proteins have not evolved for maximal thermal stability. Some are only marginally stable, as for example, the DNA-binding domains of p53 and its homologs, whose kinetic and thermodynamic stabilities are strongly correlated. Here, we applied high-throughput methods using a real-time PCR thermocycler to study the stability of several full-length orthologs and paralogs of the p53 family of transcription factors, which have diverse functions, ranging from tumour suppression to control of developmental processes. From isothermal denaturation fluorimetry and differential scanning fluorimetry, we found that full-length proteins showed the same correlation between kinetic and thermodynamic stability as their isolated DNA-binding domains. The stabilities of the full-length p53 orthologs were marginal and correlated with the temperature of their organism, paralleling the stability of the isolated DNA-binding domains. Additionally, the paralogs p63 and p73 were significantly more stable and long-lived than p53. The short half-life of p53 orthologs and the greater persistence of the paralogs may be biologically relevant.

  1. Application of biomarkers in Epaulet grouper (Epinephelus stoliczkae) to assess chromium pollution in the Chabahar Bay and Gulf of Oman

    Energy Technology Data Exchange (ETDEWEB)

    Sadeghi, Parvin, E-mail: parvin.sadeghi@gmail.com [Marine Biology Department, Marine Science Faculty, Chabahar Maritime University, Chabahar (Iran, Islamic Republic of); Kazerouni, Faranak [Department of Laboratory Medicine, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Savari, Ahmad; Movahedinia, Abdolali; Safahieh, Alireza [Marine Biology Department, Marine and Oceanic Science Faculty, Khorramshahr University of Marine Science and Technology, Khorramshahr (Iran, Islamic Republic of); Ajdari, Daniel [Iranian Fisheries Research Organization, Tehran (Iran, Islamic Republic of)

    2015-06-15

    In the present study plasma levels of erythropoietin (EPO) hormone and kidney histological changes were assessed as biomarkers to evaluate the chromium pollution in Epaulet grouper (Epinephelus stoliczkae) obtained from different areas in Chabahar Bay and Gulf of Oman. Chemical analyses included the evaluation of chromium in the fish kidney tissue and sediment. The highest and lowest concentrations of chromium were measured in the kidney of fish and sediment collected from Konarak (47.53 ± 1.23 and 110 ± 1.4 μg g{sup –1}) and the mouth of Chabahar Bay (3.43 ± 1.31 and 13.5 ± 3.23 μg g{sup –1}), respectively. There was significant difference (P < 0.05) of EPO plasma levels between Konarak, Beris and Ramin stations with the mouth of Chabahar Bay as the cleanest station. Reduction of Bowman's space, occlusion of the tubule lumen, leukocytes infiltration, melanomacrophage centers aggregation, nuclear vacuolation, nuclei hypertrophy of tubule cells, necrosis of the tubules, lifting of the tubular basement membrane and dilatation of glomerular capillaries were the most alterations observed in the kidney. The HAI values of Epaulet grouper from Konarak, Beris and Ramin stations were significantly higher than other stations (P < 0.05). It was concluded that selected biomarkers as a first investigation could be useful tools to environmental biomonitoring programs. - Highlights: • Plasma EPO level and kidney HAI were assessed as Cr biomarkers in E. stoliczkae. • Chromium was measured in the sediment and kidney of E. stoliczkae in the Gulf of Oman. • Highest Cr concentration was in the sediment and E. stoliczkae kidney from Konarak. • The analyzed biomarkers in E. stoliczkae are suitable to monitor Cr pollution.

  2. Application of biomarkers in Epaulet grouper (Epinephelus stoliczkae) to assess chromium pollution in the Chabahar Bay and Gulf of Oman

    International Nuclear Information System (INIS)

    In the present study plasma levels of erythropoietin (EPO) hormone and kidney histological changes were assessed as biomarkers to evaluate the chromium pollution in Epaulet grouper (Epinephelus stoliczkae) obtained from different areas in Chabahar Bay and Gulf of Oman. Chemical analyses included the evaluation of chromium in the fish kidney tissue and sediment. The highest and lowest concentrations of chromium were measured in the kidney of fish and sediment collected from Konarak (47.53 ± 1.23 and 110 ± 1.4 μg g–1) and the mouth of Chabahar Bay (3.43 ± 1.31 and 13.5 ± 3.23 μg g–1), respectively. There was significant difference (P < 0.05) of EPO plasma levels between Konarak, Beris and Ramin stations with the mouth of Chabahar Bay as the cleanest station. Reduction of Bowman's space, occlusion of the tubule lumen, leukocytes infiltration, melanomacrophage centers aggregation, nuclear vacuolation, nuclei hypertrophy of tubule cells, necrosis of the tubules, lifting of the tubular basement membrane and dilatation of glomerular capillaries were the most alterations observed in the kidney. The HAI values of Epaulet grouper from Konarak, Beris and Ramin stations were significantly higher than other stations (P < 0.05). It was concluded that selected biomarkers as a first investigation could be useful tools to environmental biomonitoring programs. - Highlights: • Plasma EPO level and kidney HAI were assessed as Cr biomarkers in E. stoliczkae. • Chromium was measured in the sediment and kidney of E. stoliczkae in the Gulf of Oman. • Highest Cr concentration was in the sediment and E. stoliczkae kidney from Konarak. • The analyzed biomarkers in E. stoliczkae are suitable to monitor Cr pollution

  3. Removal of Chromium and Lead from Industrial Wastewater Using

    Directory of Open Access Journals (Sweden)

    Mohamed Hilal

    2013-04-01

    Full Text Available In this research an attempt is made on the ability of aerobic treatment of synthetic solutions containing lead and chromium using effective microorganisms within the reactor. To achieve the desired objectives of the research, synthetic aqueous solutions of lead and chromium was used in the concentration of chromium and lead ions of 5, 10,50 and 100 mg / l .The work was done at constant pH equal to 4.5 and temperature of 30 ± 1 º C. Effective microorganisms solutions was added to the reactor at Vol.% of 1/50 ,1/100 ,1/500 and 1/1000, with retention time was 24 hours to measure the heavy metals concentration the atomic absorption device was used. The experimental results showed that each 1mg / l of lead and chromium ions need 24 mg of effective microorganisms to achieve removal of 92.0% and 82.60% for lead and chromium respectively. Increasing the concentration of effective microorganisms increases the surface of adsorption and thus increasing the removal efficiency. It is found that the microorganisms activity occur in the first five hours of processing and about 94% of adsorption capacity of biomass will take place. It is also found the selectivity of microorganisms to lead ions is higher than for chromium ions.

  4. Evaluating trivalent chromium toxicity on wild terrestrial and wetland plants.

    Science.gov (United States)

    Lukina, A O; Boutin, C; Rowland, O; Carpenter, D J

    2016-11-01

    Elevated chromium levels in soil from mining can impact the environment, including plants. Mining of chromium is concentrated in South Africa, several Asian countries, and potentially in Northern Ontario, Canada, raising concerns since chromium toxicity to wild plants is poorly understood. In the first experiment, concentration-response tests were conducted to evaluate effects of chromium on terrestrial and wetland plants. Following established guidelines using artificial soil, seeds of 32 species were exposed to chromium (Cr(3+)) at concentrations simulating contamination (0-1000 mg kg(-1)). This study found that low levels of chromium (250 mg kg(-1)) adversely affected the germination of 22% of species (33% of all families), while higher levels (500 and 1000 mg kg(-1)) affected 69% and 94% of species, respectively, from 89% of the families. Secondly, effects on seedbanks were studied using soil collected in Northern Ontario and exposed to Cr(3+) at equivalent concentrations (0-1000 mg kg(-1)). Effects were less severe in the seedbank study with significant differences only observed at 1000 mg kg(-1). Seeds exposed to Cr(3+) during stratification were greatly affected. Seed size was a contributing factor as was possibly the seed coat barrier. This study represents an initial step in understanding Cr(3+) toxicity on wild plants and could form the basis for future risk assessments. PMID:27543852

  5. Lime enhanced chromium removal in advanced integrated wastewater pond system.

    Science.gov (United States)

    Tadesse, I; Isoaho, S A; Green, F B; Puhakka, J A

    2006-03-01

    The removal of trivalent chromium from a combined tannery effluent in horizontal settling tanks and subsequent Advanced Integrated Wastewater Pond System (AIWPS) reactors was investigated. The raw combined effluent from Modjo tannery had pH in the range of 11.2-12. At this pH, a trivalent chromium removal of 46-72% was obtained in the horizontal settling tanks after a one-day detention time. Trivalent chromium precipitated as chromium hydroxide, Cr(OH)3. 58-95% Cr(III) was removed in the advanced facultative pond (AFP) where the water column pH of 7.2-8.4 was close to pH 8, which is the optimum precipitation pH for trivalent chromium. Chromium removals in the secondary facultative pond (SFP) and maturation pond (MP) were 30-50% and 6-16%, respectively. With Cr(III) concentration of 0.2-0.8 mg/l in the final treated effluent, the AIWPS preceded by horizontal settling tanks produced effluent that could easily meet most of the current Cr(III) discharge limits to receive water bodies.

  6. p53 and its isoforms in cancer

    OpenAIRE

    Bourdon, J-C

    2007-01-01

    p53, p63 and p73 are members of the p53 gene family involved in development, differentiation and response to cellular stress. p53 gene is a transcription factor essential for the prevention of cancer formation. The p53 pathway is ubiquitously lost in human cancer either by p53 gene mutation (60% of cancers) or by lost of cell signalling upstream and downstream of p53 in the remaining cancers expressing WTp53 gene. As p53 pathway inactivation is a common denominator to all cancers, the underst...

  7. Restoring wtp53 activity in HIPK2 depleted MCF7 cells by modulating metallothionein and zinc.

    Science.gov (United States)

    Puca, Rosa; Nardinocchi, Lavinia; Bossi, Gianluca; Sacchi, Ada; Rechavi, Gideon; Givol, David; D'Orazi, Gabriella

    2009-01-01

    The maintenance of p53 transactivation activity is important for p53 apoptotic function. We have shown that stable knockdown of HIPK2 induces p53 misfolding with inhibition of p53 target gene transcription. In this study we established a lentiviral-based system for doxycyclin (Dox)-induced conditional interference of HIPK2 expression to evaluate the molecular mechanisms involved in p53 deregulation. We found that HIPK2 knockdown induced metallothionein 2A (MT2A) upregulation as assessed by RT-PCR analysis, increased promoter acetylation, and increased promoter luciferase activity. The MT2A upregulation correlated with resistance to Adriamycin (ADR)-driven apoptosis and with p53 inhibition. Thus, acute knockdown of HIPK2 (HIPK2i) induced misfolded p53 protein in MCF7 breast cancer cells and inhibited p53 DNA-binding and transcription activities in response to ADR treatment. Previous works show that MT may modulate p53 activity through zinc exchange. Here, we found that inhibition of MT2A expression by siRNA in the HIPK2i cells restored p53 transcription activity. Similarly zinc supplementation to HIPK2i cells restored p53 transcription activity and drug-induced apoptosis. These data support the notion that MT2A is involved in p53 deregulation and strengthen the possibility that combination of chemotherapy and zinc might be useful to treat tumors with inactive wtp53. PMID:18996371

  8. Accurate quantification of total chromium and its speciation form Cr(VI) in water by ICP-DRC-IDMS and HPLC/ICP-DRC-IDMS.

    Science.gov (United States)

    Markiewicz, Barbara; Komorowicz, Izabela; Barałkiewicz, Danuta

    2016-05-15

    Two analytical procedures have been developed for the determination of total chromium (TCr) and its highly toxic species, i.e. Cr(VI) in water samples using the following methods: inductively coupled plasma dynamic reaction cell isotope dilution mass spectrometry (ICP-DRC-IDMS) and high performance liquid chromatography inductively coupled plasma dynamic reaction cell isotope dilution mass spectrometry (HPLC/ICP-DRC-IDMS). Spectral interferences, predominantly occurring in chromium determination, were removed using a dynamic reaction cell (DRC). The presented procedures facilitate the quantification of trace amounts - below 1 µg L(-1) of TCr and individual Cr species - in various water matrices including drinking water and still bottled water with different mineral composition. Special attention has been paid to the adequate preparation of isotopically enriched (53)Cr(VI) standard solution in order to avoid artifacts in chromium speciation. Both procedures were fully validated as well as establishing the traceability and estimation of the uncertainty of measurement were carried out. Application of all of the above mentioned elements and of the isotope dilution technique, which provides the highest quality of metrological traceability, allowed to obtain reliable and high quality results of chromium determination in water samples. Additionally, the comparison of two methods: HPLC/ICP-DRC-MS and HPLC/ICP-DRC-IDMS for Cr(VI) determination, was submitted basing on the validation parameters. As a result, the lower values for these parameters were obtained using the second method. PMID:26992546

  9. Experimental skin deposition of chromium on the hands following handling of samples of leather and metal

    DEFF Research Database (Denmark)

    Bregnbak, David; Thyssen, Jacob P.; Jellesen, Morten Stendahl;

    2016-01-01

    Background: Chromium is an important skin sensitizer. Exposure to it has been regulated in cement, and recently in leather. Studies on the deposition of chromium ions on the skin as a result of handling different chromium-containing materials are sparse, but could improve the risk assessment...... of contact sensitization and allergic contact dermatitis caused by chromium. Objectives: To determine whether the handling of chromium-containing samples of leather and metal results in the deposition of chromium onto the skin. Methods: Five healthy volunteers participated. For 30 min, they handled samples...... of leather and metal known to contain and release chromium. Skin deposition of chromium was assessed with the acid wipe sampling technique. Results: Acid wipe sampling of the participants' fingers showed chromium deposition on the skin in all participants who had been exposed to leather (range 0.01–0.20 µg...

  10. USE OF TWO DIGESTION METHODS IN THE EVALUATION OF CHROMIUM CONTENT IN CATTLE'S MEAT SUPPLEMENTED WITH CHROMIUM CHELATES

    OpenAIRE

    R. L. T. Andrade; P.S.A. Moreira; R. Arruda; F. J. Lourenço; C. Palhari, F. F. Faria, V. B. Arevalo; Faria, F. F.; V. B. Arevalo

    2015-01-01

    The present study aimed to analyze the chromium content in beef using two digestion methods. There were used samples from 24 18-month-old male cattle, and twelve of them were supplemented and twelve were not supplemented with chromium chelate. These samples were evaluated by atomic absorption spectroscopy, previously submitted to digestion method using nitric acid (65%) with hydrogen peroxide (35%) and to digestion method, using solution of nitric perchloric acid in the proportion 3:1. Immedi...

  11. Activation of bentonite to remove the chromium from waste water produced by panning industry, and studying the chromium recovery efficiency

    International Nuclear Information System (INIS)

    The fast development of tanning industry led to an increase in environmental problems resulting from discharging its wastes to the surrounding environment. Thus solving this problem became one of the most important aims that the researchers work on. The chromium content of the industrial water wastes of the tanning industry considered as the main pollutant for the environment. The Aleppo Bentonite is used in early research to remove the chromium from the industrial waste water.The current research aims to find a method to activate the Aleppo Bentonite in order to increase the effective removal of chromium from the industrial waste water which is produced by tanning industry, as well as to specify the optimal conditions for chromium recovery.This study used the Aleppo Bentonite, whose origin is Tal Ajar-Aleppo to study the activation aspects using Sulfuric Acid, Hydrochloric Acid and Nitric Acid, in addition to study the recovery aspects using the same acids and hydrogen peroxide and to specify the optimal conditions for chromium recovery through applying some experiments based on three main factors: concentration, settling time and temperature.It was observed from the applied experiments that it is possible to recover chromium from Bentonite efficiently up to (80% - 90%) by treating the Bentonite with hydrogen peroxide(33% concentration) at room temperature, or by treating it with hydrogen peroxide(8.25% concentration) at 75oC, while the settling time factor proved that full recovery of chromium is obtained during the first hour, and increasing the time factor does not affect the efficiency of chromium recovery. (author)

  12. P53-specific T cell responses in patients with malignant and benign ovarian tumors : Implications for p53 based immunotherapy

    NARCIS (Netherlands)

    Lambeck, Annechien; Leffers, Ninke; Hoogeboom, Baukje-Nynke; Sluiter, Wim; Hamming, Ineke; Klip, Harry; ten Hoor, Klaske; Esajas, Martha; van Oven, Magda; Drijfhout, Jan-Wouter; Platteel, Inge; Offringa, Rienk; Hollema, Harry; Melief, Kees; van der Burg, Sjoerd; van der Zee, Ate; Daemen, Toos; Nijman, Hans

    2007-01-01

    Despite intensive treatment, 70% of the ovarian cancer patients will develop recurrent disease, emphasizing the need for new approaches such as immunotherapy. A promising antigenic target for immunotherapy in ovarian cancer is the frequently overexpressed p53 protein. The aim of the study was to eva

  13. The emerging role of p53 in exercise metabolism.

    Science.gov (United States)

    Bartlett, Jonathan D; Close, Graeme L; Drust, Barry; Morton, James P

    2014-03-01

    of reduced carbohydrate availability in association with enhanced upstream signalling through 5'adenosine monophosphate-activated protein kinase but not p38 mitogen-activated protein kinase. In this way, undertaking regular exercise in carbohydrate restricted states may therefore be a practical approach to achieve the physiological benefits of consistent p53 signalling. Although our knowledge of p53 in exercise metabolism has advanced considerably, much of our current understanding of p53 regulation and associated targets is derived from various non-muscle cells and tissues. As such, many fundamental questions remain unanswered in contracting skeletal muscle. Detailed studies concerning the time-course of p53 activation (including additional post-translational modifications and subsequent subcellular translocation), as well as the effects of exercise modality (endurance versus resistance), intensity, duration, fibre type, age, training status and nutrient availability, must now be performed so that we can optimise exercise prescription guidelines to strategically target p53 signalling. The emerging role of p53 in skeletal muscle metabolism therefore represents a novel and exciting research area for exercise and muscle physiologists. PMID:24264057

  14. Low energy spin excitations in chromium metal

    Energy Technology Data Exchange (ETDEWEB)

    Pynn, R. [Los Alamos National Lab., NM (United States); Azuah, R.T. [Hahn-Meitner-Inst., Berlin (Germany); Stirling, W.G. [Univ. of Liverpool (United Kingdom). Dept. of Physics; Kulda, J. [Inst. Laue Langevin, Grenoble (France)

    1997-12-31

    Neutron scattering experiments with full polarization analysis have been performed with a single crystal of chromium to study the low-energy spin fluctuations in the transverse spin density wave (TSDW) state. A number of remarkable results have been found. Inelastic scattering observed close to the TSDW satellite positions at (1 {+-} {delta},0,0) does not behave as expected for magnon scattering. In particular, the scattering corresponds to almost equally strong magnetization fluctuations both parallel and perpendicular to the ordered moments of the TSDW phase. As the Neel temperature is approached from below, scattering at the commensurate wavevector (1,0,0) increases in intensity as a result of critical scattering at silent satellites (1,0, {+-} {delta}) being included within the spectrometer resolution function. This effect, first observed by Sternlieb et al, does not account for all of the inelastic scattering around the (1,0,0) position, however, Rather, there are further collective excitations, apparently emanating from the TSDW satellites, which correspond to magnetic fluctuations parallel to the ordered TSDW moments. These branches have a group velocity that is close to that of (1,0,0) longitudinal acoustic (LA) phonons, but assigning their origin to magneto-elastic scattering raises other unanswered questions.

  15. Effects of cobalt-chromium everolimus eluting stents or bare metal stent on fatal and non-fatal cardiovascular events

    DEFF Research Database (Denmark)

    Valgimigli, Marco; Sabaté, Manel; Kaiser, Christoph;

    2014-01-01

    eluting stents with bare metal stents were selected. The principal investigators whose trials met the inclusion criteria provided data for individual patients. PRIMARY OUTCOMES: The primary outcome was cardiac mortality. Secondary endpoints were myocardial infarction, definite stent thrombosis, definite......OBJECTIVES: To examine the safety and effectiveness of cobalt-chromium everolimus eluting stents compared with bare metal stents. DESIGN: Individual patient data meta-analysis of randomised controlled trials. Cox proportional regression models stratified by trial, containing random effects, were...... or probable stent thrombosis, target vessel revascularisation, and all cause death. RESULTS: The search yielded five randomised controlled trials, comprising 4896 participants. Compared with patients receiving bare metal stents, participants receiving cobalt-chromium everolimus eluting stents had...

  16. TP53 Mutations in Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Akira Mogi

    2011-01-01

    Full Text Available The tumor suppressor gene TP53 is frequently mutated in human cancers. Abnormality of the TP53 gene is one of the most significant events in lung cancers and plays an important role in the tumorigenesis of lung epithelial cells. Human lung cancers are classified into two major types, small cell lung cancer (SCLC and nonsmall cell lung cancer (NSCLC. The latter accounts for approximately 80% of all primary lung cancers, and the incidence of NSCLC is increasing yearly. Most clinical studies suggest that NSCLC with TP53 alterations carries a worse prognosis and may be relatively more resistant to chemotherapy and radiation. A deep understanding of the role of TP53 in lung carcinogenesis may lead to a more reasonably targeted clinical approach, which should be exploited to enhance the survival rates of patients with lung cancer. This paper will focus on the role of TP53 in the molecular pathogenesis, epidemiology, and therapeutic strategies of TP53 mutation in NSCLC.

  17. The expanding regulatory universe of p53 in gastrointestinal cancer.

    Science.gov (United States)

    Fesler, Andrew; Zhang, Ning; Ju, Jingfang

    2016-01-01

    Tumor suppresser gene TP53 is one of the most frequently deleted or mutated genes in gastrointestinal cancers. As a transcription factor, p53 regulates a number of important protein coding genes to control cell cycle, cell death, DNA damage/repair, stemness, differentiation and other key cellular functions. In addition, p53 is also able to activate the expression of a number of small non-coding microRNAs (miRNAs) through direct binding to the promoter region of these miRNAs.  Many miRNAs have been identified to be potential tumor suppressors by regulating key effecter target mRNAs. Our understanding of the regulatory network of p53 has recently expanded to include long non-coding RNAs (lncRNAs). Like miRNA, lncRNAs have been found to play important roles in cancer biology.  With our increased understanding of the important functions of these non-coding RNAs and their relationship with p53, we are gaining exciting new insights into the biology and function of cells in response to various growth environment changes. In this review we summarize the current understanding of the ever expanding involvement of non-coding RNAs in the p53 regulatory network and its implications for our understanding of gastrointestinal cancer.

  18. Hexavalent Chromium Reduction and Its Distribution in the Cell and Medium by Chromium Resistant Fusarium solani

    Directory of Open Access Journals (Sweden)

    Mousumi Sen

    2013-01-01

    Full Text Available In the present work, batch biosorption of Cr(VI was studied using the fungal strain isolated from soil. The fungal strain was characterized as Fusarium solani. The total Cr distribution in the biomass (fungus and in the media obtained from the experiment conducted at 500 mg l -1 initial Cr(VI concentration and pH 5.0. The results indicated both intracellular and extracellular accumulation and enzymatic reduction of Cr(VI and this was supported by the Transmission Electron Microscopic (TEM observation at the same Cr(VI concentration and pH value. Chromium elution from Fusarium solani containing Cr was then tried out using a number of chromium eluting reagents and a maximum Cr could be eluted using 0.5N sodium hydroxide solution without destructing the biomass structure. The total Cr was recovered by pH adjustment from both biomass and media was found to be 44% of the initial Cr(VI concentration (500 mg l-1.

  19. Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53

    Science.gov (United States)

    Martinez-Zapien, Denise; Ruiz, Francesc Xavier; Poirson, Juline; Mitschler, André; Ramirez-Ramos, Juan; Forster, Anne; Cousido-Siah, Alexandra; Masson, Murielle; Pol, Scott Vande; Podjarny, Alberto; Travé, Gilles; Zanier, Katia

    2015-01-01

    Summary The p53 pro-apoptotic tumor suppressor is mutated or functionally altered in most cancers. In epithelial tumors induced by “high-risk” mucosal Human Papillomaviruses (hrm-HPVs), including human cervical carcinoma and a growing number of head-and-neck cancers 1, p53 is degraded by the viral oncoprotein E6 2. In this process, E6 binds to a short LxxLL consensus sequence within the cellular ubiquitin ligase E6AP 3. Subsequently, the E6/E6AP heterodimer recruits and degrades p53 4. Neither E6 nor E6AP are separately able to recruit p53 3,5, and the precise mode of assembly of E6, E6AP and p53 is unknown. Here, we solved the crystal structure of a ternary complex comprising full-length HPV16 E6, the LxxLL motif of E6AP and the core domain of p53. The LxxLL motif of E6AP renders the conformation of E6 competent for interaction with p53 by structuring a p53-binding cleft on E6. Mutagenesis of critical positions at the E6-p53 interface disrupts p53 degradation. The E6-binding site of p53 is distal from previously described DNA- and protein-binding surfaces of the core domain. This suggests that, in principle, E6 may avoid competition with cellular factors by targeting both free and bound p53 molecules. The E6/E6AP/p53 complex represents a prototype of viral hijacking of both the ubiquitin-mediated protein degradation pathway and the p53 tumor suppressor pathway. The present structure provides a framework for the design of inhibitory therapeutic strategies against HPV-mediated oncogenesis. PMID:26789255

  20. Transcriptional Activation by Wild-Type But Not Transforming Mutants of the p53 Anti-Oncogene

    OpenAIRE

    Raycroft, Loretta; Wu, Hongyun; Lozano, Guillermina

    1990-01-01

    The protein encoded by the wild-type p53 proto-oncogene has been shown to suppress transformation, whereas certain mutations that alter p53 become transformation competent. Fusion proteins between p53 and the GAL4 DNA binding domain were made to anchor p53 to a DNA target sequence and to allow measurement of transcriptional activation of a reporter plasmid. The wild-type p53 stimulated transcription in this assay, but two transforming mutations in p53 were unable to act as transcriptional act...

  1. Acetylation Is Indispensable for p53 Activation

    OpenAIRE

    Tang, Yi; Zhao, Wenhui; Chen, Yue; Zhao, Yingming; Gu, Wei

    2008-01-01

    The activation of the tumor suppressor p53 facilitates the cellular response to genotoxic stress; however, the p53 response can only be executed if its interaction with its inhibitor Mdm2 is abolished. There have been conflicting reports on the question of whether p53 posttranslational modifications, such as phosphorylation or acetylation, are essential or only play a subtle, fine-tuning role in the p53 response. Thus, it remains unclear whether p53 modification is absolutely required for its...

  2. Regulation of Mutant p53 Protein Expression

    OpenAIRE

    Vijayakumaran, Reshma; Tan, Kah Hin; Miranda, Panimaya Jeffreena; Haupt, Sue; Haupt, Ygal

    2015-01-01

    For several decades, p53 has been detected in cancer biopsies by virtue of its high protein expression level which is considered indicative of mutation. Surprisingly, however, mouse genetic studies revealed that mutant p53 is inherently labile, similar to its wild type (wt) counterpart. Consistently, in response to stress conditions, both wt and mutant p53 accumulate in cells. While wt p53 returns to basal level following recovery from stress, mutant p53 remains stable. In part, this can be e...

  3. Electron transfer. 75. Reduction of carboxylato-bound chromium(V) with vanadium(IV). Intervention of chromium(IV)

    International Nuclear Information System (INIS)

    The chelated (carboxylato)chromium(V) anion bis(2-hydroxy-2-ethylbutyrato)oxochromate(V) (I), [(Lig)2Cr(O)]-, reacts with oxovanadium(IV) to form a strongly absorbing species (lambda/sub max/ = 515 nm; epsilon = 1.7 x 103 M-1) in the presence of 2-hydroxy-2-ethylbutyric acid buffers (pH 2-4). EPR data support 1:1 stoichiometry with VO2+ in deficiency, indicating the formation of a chromium(IV) species by reduction. With excess VO2+ a chromium(III) product was obtained. Spectral and ion-exchange properties of this product correspond to those observed for the titanium(III) and iron(II) reductions of chromium(V) and are consistent with the formulation of the product as a bis(hydroxycarboxylate) chelate of (H2O)2Cr/sup III/. With excess vanadium(IV), the reaction exhibits triphasic kinetics. The remaining step of the reaction is the reduction of the chromium(IV) intermediate with VO2+. Rates for all steps increase with decreasing [H+] and level off at low [H+]. The limiting rate constants for the formation of the chromium(IV) intermediate by the (Lig)3Cr(O)2- and (Lig)2Cr(O)- pathways are 2.8 x 103 and 2.2 x 102 M-1s-1. The bimolecular limiting rate constant for the reduction of chromium(IV) is computed to be 7.7 x 102 M-1 s-1. 33 references, 7 tables

  4. Application of artificial neural network (ANN in Biosorption modeling of Chromium (VI from aqueous solutions

    Directory of Open Access Journals (Sweden)

    F Mohammadi

    2016-03-01

    Full Text Available Background and Objectives: In this work, biosorption of hexavalent chromium from aqueous solution with excess municipal sludge was studied. Moreover, the performance of neural networks to predict the biosorption rate was investigated. Materials and Methods: The effect of operational parameters including initial metal concentration, initial pH, agitation speed, adsorbent dosage, and agitation time on the biosorption of chromium was assessed in a batch system. A part of the experimental results was modeled using Feed-Forward Back propagation Neural Network (FFBP-ANN. Another part of the test results was simulated to assess the model accuracy. Transfer function in the hidden layers and output layers and the number of neurons in the hidden layers were optimized. Results: The maximum removal of chromium obtained from batch studies was more than 96% in 90 mg/L initial concentration, pH 2, agitation speed 200 rpm and adsorbent dosage 4 g/L. Maximum biosorption capacity was 41.69 mg/g. Biosorption data of Cr(VI are described well by Freundlich isotherm model and adsorption kinetic followed pseudo-second order model.  Tangent sigmoid function determined was the most appropriate transfer function in the hidden and output layer. The optimal number of neurons in hidden layers was 13. Predictions of model showed excellent correlation (R=0.984 with the target vector. Simulations performed by the developed neural network model showed good agreement with experimental results. Conclusion: Overall, it can be concluded that excess municipal sludge performs well for the removal of Cr ions from aqueous solution as a biological and low cost biosorbent. FFBP-ANN is an appropriate technique for modeling, estimating, and prediction of biosorption process If the Levenberg-Marquardt training function, tangent sigmoid transfer function in the hidden and output layers and the number of neurons is between 1.6 to 1.8 times the input data, proper predication results could be

  5. Low-chromium reduced-activation ferritic steels for fusion

    Energy Technology Data Exchange (ETDEWEB)

    Klueh, R.L.; Alexander, D.J.; Kenik, E.A. [Oak Ridge National Laboratory, TN (United States)

    1996-04-01

    Development of reduced-activation ferritic steels has concentrated on high-chromium (8-10 wt% Cr) steels. However, there are advantages for a low-chromium steel, and initial ORNL studies on reduced-activation steels were on compositions with 2.25 to 12% Cr. Those studies showed an Fe-2.25Cr-2W-0.25V-0.1C (2 1/4Cr-2WV) steel to have the highest strenglth of the steels studied. Although this steel had the best strength, Charpy impact properties were inferior to those of an Fe-9Cr-2W-0.25V-0.07Ta-0.1C (9Cr-2WVTa) and an Fe-2.25Cr-2W-0.1C (2 1/4Cr-2W) steel. Therefore, further development of the low-chromium Cr-W steels was required. These results indicate that it is possible to develop low-chromium reduced-activation ferritic steels that have tensile and impact properties as good or better than those of high-chromium (7-9% Cr) steels. Further improvement of properties should be possible by optimizing the composition.

  6. Bioaccumulation and biosorption of chromium by Aspergillus niger MTCC 2594.

    Science.gov (United States)

    Sandana Mala, John Geraldine; Unni Nair, Balachandran; Puvanakrishnan, Rengarajulu

    2006-06-01

    Chromium toxicity is of prime concern due to chrome tanning processes in the leather sector. Chrome tanning results in the discharge of toxic levels of chromium causing pollution hazards. Chromium levels of Cr(III) and Cr(VI) were high above permissible limits in chrome samples after chrome tanning. The potential of Aspergillus niger MTCC 2594 to accumulate chromium as well as its biosorption capacity is investigated in this study. Bioaccumulation of Cr(III) and Cr(VI) in the spent chrome liquor has resulted in a 75-78% reduction of the initial Cr content in 24-36 h. A. niger biomass is found to be very effective in the biosorption of Cr(III) and Cr(VI) in spent chrome liquor. Maximum adsorption of 83% for biosorption of Cr(III) at 48 h and 79% of Cr(VI) at 36 h in spent chrome liquor is observed. The biosorption characteristics fit well with Langmuir and Freundlich isotherms and the adsorption parameters are evaluated. The biosorption of Cr also follows Lagergren kinetics. A. niger biomass is effectively used for the biosorption of chromium with 79-83% Cr removal in 36-48 h.

  7. Chromium propionate enhances adipogenic differentiation of bovine intramuscular adipocytes

    Directory of Open Access Journals (Sweden)

    Rebecca eTokach

    2015-09-01

    Full Text Available In vitro experiments were performed to determine the effects of increasing concentrations of chromium propionate on mRNA and protein abundance of different enzymes and receptors. Intramuscular and subcutaneous preadipocytes and bovine satellite cells were isolated from the longissimus muscle to determine the effect of treatment on glucose transporter type 4 (GLUT4 and peroxisome proliferator-activated receptor γ mRNA and GLUT4 protein abundance. Preadipocyte cultures were treated with differentiation media plus either sodium propionate or different concentrations of chromium propionate (CrPro for 96, 120, and 144 h before harvest. This study indicated adipogenesis of the bovine intramuscular adipocytes were more sensitive to the treatment of chromium propionate as compared to subcutaneous adipocytes. Enhancement of adenosine monophosphate-activated protein kinase and GLUT4 mRNA by CrPro treatment may enhance glucose uptake in intramuscular adipocytes. Chromium propionate decreased GLUT4 protein levels in muscle cell cultures suggesting those cells have increased efficiency of glucose uptake due to exposure to increased levels of CrPro. In contrast, each of the two adipogenic lines had opposing responses to the CrPro. It appeared that CrPro had the most stimulative effect of GLUT4 response in the intramuscular adipocytes as compared to subcutaneous adipocytes. These findings indicated opportunities to potentially augment marbling in beef cattle fed chromium propionate during the finishing phase.

  8. Anthropogenic chromium emissions in china from 1990 to 2009.

    Science.gov (United States)

    Cheng, Hongguang; Zhou, Tan; Li, Qian; Lu, Lu; Lin, Chunye

    2014-01-01

    An inventory of chromium emission into the atmosphere and water from anthropogenic activities in China was compiled for 1990 through to 2009. We estimate that the total emission of chromium to the atmosphere is about 1.92×10⁵ t. Coal and oil combustion were the two leading sources of chromium emission to the atmosphere in China, while the contribution of them showed opposite annual growth trend. In total, nearly 1.34×10⁴ t of chromium was discharged to water, mainly from six industrial categories in 20 years. Among them, the metal fabrication industry and the leather tanning sector were the dominant sources of chromium emissions, accounting for approximately 68.0% and 20.0% of the total emissions and representing increases of 15.6% and 10.3% annually, respectively. The spatial trends of Cr emissions show significant variation based on emissions from 2005 to 2009. The emission to the atmosphere was heaviest in Hebei, Shandong, Guangdong, Zhejiang and Shanxi, whose annual emissions reached more than 1000t for the high level of coal and oil consumption. In terms of emission to water, the largest contributors were Guangdong, Jiangsu, Shandong and Zhejiang, where most of the leather production and metal manufacturing occur and these four regions accounted for nearly 47.4% of the total emission to water. PMID:24505309

  9. Anthropogenic chromium emissions in china from 1990 to 2009.

    Directory of Open Access Journals (Sweden)

    Hongguang Cheng

    Full Text Available An inventory of chromium emission into the atmosphere and water from anthropogenic activities in China was compiled for 1990 through to 2009. We estimate that the total emission of chromium to the atmosphere is about 1.92×10⁵ t. Coal and oil combustion were the two leading sources of chromium emission to the atmosphere in China, while the contribution of them showed opposite annual growth trend. In total, nearly 1.34×10⁴ t of chromium was discharged to water, mainly from six industrial categories in 20 years. Among them, the metal fabrication industry and the leather tanning sector were the dominant sources of chromium emissions, accounting for approximately 68.0% and 20.0% of the total emissions and representing increases of 15.6% and 10.3% annually, respectively. The spatial trends of Cr emissions show significant variation based on emissions from 2005 to 2009. The emission to the atmosphere was heaviest in Hebei, Shandong, Guangdong, Zhejiang and Shanxi, whose annual emissions reached more than 1000t for the high level of coal and oil consumption. In terms of emission to water, the largest contributors were Guangdong, Jiangsu, Shandong and Zhejiang, where most of the leather production and metal manufacturing occur and these four regions accounted for nearly 47.4% of the total emission to water.

  10. Enhancement of chromium uptake in tanning using oxazolidine.

    Science.gov (United States)

    Sundarapandiyan, S; Brutto, Patrick E; Siddhartha, G; Ramesh, R; Ramanaiah, B; Saravanan, P; Mandal, A B

    2011-06-15

    Monocyclic and bicyclic oxazolidines were offered at three different junctures of chrome tanning process viz. prior to BCS offer, along with BCS and after basification. It was found that oxazolidine when offered after basification brought about better chromium uptake and reduction of chromium load in the wastewater. Offer of oxazolidine was also varied. Increase in offer of oxazolidine from 0.25% to 1% was found to enhance the chromium uptake and decrease the chromium load in wastewater. But the increase in uptake was not proportionate to the increase in oxazolidine offer more than 0.75%. Offer of 1% Zoldine ZA 78 (monocyclic oxazolidine) and Zoldine ZE (bicyclic oxazolidine) after basification brought about 63.4% and 73.1% enhancement in chrome content in leather compared to control where oxazolidine was not offered. The tone of the wetblue was found to be altered moderately. However this did not call for any process adjustments in wet-finishing. The oxazolidine treated leathers were found to be immensely fuller and tighter. It was found experimentally that offer of 1% of oxazolidine facilitated reduction in the offer of syntans administered for filling and grain tightening by around 46%. Oxazolidine could bring about significant reduction in cost of chemicals apart from resulting environmental benefits due to enhancement of chromium uptake during tanning. PMID:21536383

  11. Systems-level analysis of the regulation and function of p53 dynamics in cancer

    Science.gov (United States)

    Batchelor, Eric

    Living cells use complex signaling pathways to detect environmental stimuli and generate appropriate responses. As methods for quantifying intracellular signaling have improved, several signaling pathways have been found to transmit information using signals that pulse in time. The transcription factor p53 is a key tumor suppressor and stress-response regulator that exhibits pulsatile dynamics. In response to DNA double-strand breaks, the concentration of p53 in the cell nucleus increases in pulses with a fixed amplitude, duration, and period; the mean number of pulses increases with DNA damage. p53 regulates the expression of over 100 target genes involved in a range of cellular stress responses including apoptosis, cell cycle arrest, and changes in metabolism. p53 pulsing directly impacts p53 function: altering p53 dynamics by pharmacologically inhibiting p53 degradation changes patterns of target gene expression and cell fate. While p53 pulsing serves an important signaling function, it is less clear what it accomplishes mechanistically. Here we will describe our recent efforts to determine the impact of p53 pulsing on the dynamics and coordination of target gene expression.

  12. The Behaviour of Chromium Isotopes during the Oxidative Weathering of Ultramafic Rocks

    DEFF Research Database (Denmark)

    Paulukat, Cora Stefanie; Døssing, Lasse Nørbye; Mondal, Sisir K.;

    The chromium isotope system has been proven to be a redox-sensitve proxy in ancient and modern environmental studies (e.g. [1], [2]). In this study we investigated Cr isotope fractionation during soil formation from Archean (3.1-3.3 Ga) ultramafic rocks, intruded into metamorphic rocks of the Iron...... Ore Group in the southern Singhbhum Craton (Orissa, India)[3]. A modern weathering profile was logged in an active open cast chromite mine (Sukinda valley). The Cr isotope data of samples from the weathering profile are fractionaed. While the least weathered horizons at the base of the profile reflect...... mantle inventory values (-0.124±0.101‰ [4]), the δ53Cr values from the more weathered upper part of the profile are as low as -1.28±0.08‰, indicative of the loss of an isotopically heavy (53Cr enriched) fraction to the runoff. Mass-balance calculations show that the highly weathered horizons...

  13. Reduction of chromium oxide from slags

    Directory of Open Access Journals (Sweden)

    Gutiérrez-Paredes, J.

    2005-12-01

    Full Text Available Experimental and theoretical work were performed to estimate the effect of slag basicity and amount of reducing agents on the reduction of chromium oxide from the slag which interacted with molten steel at 1,600 °C. The slag system contained CaO, MgO, SiO2, CaF2 and Cr2O3 together with Fe-alloys (Fe-Si and Fe-Si-Mg. The CaF2 and MgO contents in the slags were 10 mass % each; Cr2O3 was 25%. The amount of the ferroalloys ranged from 12.5 to 50 g per 100 g of slag. The (CaO+MgO/SiO2 ratio was held at 1 and 2. The Cr yield was determined using both Fe-alloys as reducing agents. Some estimations were made to determine the theoretical effect of temperature, slag basicity, (CaO+MgO/SiO2, and amount of reducing agents in the slag on the chromium recovery. The FACT (Facility for the Analysis of Chemical Thermodynamics computational package is used to determine the equilibrium between the slag and molten steel.

    En el presente trabajo se realiza un estudio teórico y experimental para determinar el efecto de la basicidad de la escoria y la cantidad de agentes reductores sobre la reducción de óxidos de cromo contenidos en la escoria, la cual está en contacto con acero líquido a 1.600 °C. La escoria se prepara con los reactivos CaO, MgO, SiO2, CaF2 y ferroaleaciones (Fe-Si y Fe-Si-Mg. Los contenidos de CaF2 y MgO en la escoria son de 10 %, cada uno, y el de Cr2O3 es 25 %. La cantidad de la ferroaleación varía de 12,5 a 50 g por cada 100 g de escoria. La relación (CaO+MgO/SiO2 tiene los valores de 1 y 2. Se determina la eficiencia de recuperación de cromo empleando los dos tipos de ferroaleaciones. Se realizaron cálculos para determinar el efecto teórico de la temperatura, la basicidad de la escoria, (CaO+MgO/SiO2, y la cantidad de agentes reductores sobre la reducci

  14. A defect in the p53 response pathway induced by de novo purine synthesis inhibition.

    Science.gov (United States)

    Bronder, Julie L; Moran, Richard G

    2003-12-01

    p53 is believed to sense cellular ribonucleotide depletion in the absence of DNA strand breaks and to respond by imposition of a p21-dependent G1 cell cycle arrest. We now report that the p53-dependent G1 checkpoint is blocked in human carcinoma cell lines after inhibition of de novo purine synthesis by folate analogs inhibitory to glycinamide ribonucleotide formyltransferase (GART). p53 accumulated in HCT116, MCF7, or A549 carcinoma cells upon GART inhibition, but, surprisingly, transcription of several p53 targets, including p21cip1/waf1, was impaired. The mechanism of this defect was examined. The p53 accumulating in these cells was nuclear but was not phosphorylated at serines 6, 15, and 20, nor was it acetylated at lysines 373 or 382. The DDATHF-stabilized p53 bound to the p21 promoter in vitro and in vivo but did not activate histone acetylation over the p53 binding sites in the p21 promoter that is an integral part of the transcriptional response mediated by the DNA damage pathway. We concluded that the robust initial response of the p53 pathway to GART inhibitors is not transcriptionally propagated to target genes due to a defect in p53 post-translational modifications and a failure to open chromatin structure despite promoter binding of this unmodified p53. PMID:14517211

  15. Antigen-specific immunotherapy in ovarian cancer and p53 as tumor antigen

    NARCIS (Netherlands)

    Vermeij, Renee; Leffers, Ninke; Melief, Cornelis J.; Daemen, Toos; Nijman, Hans W.

    2012-01-01

    This review discusses the results of different immunization strategies, identifies possible drawbacks in study design and provides potential solutions for augmentation of clinical efficacy. A potential target for cancer immunotherapy is p53, as approximately 50% of ovarian cancer cells carry p53 mut

  16. Electrochemical modification of chromium surfaces using 4-nitro- and4-fluorobenzenediazonium salts

    DEFF Research Database (Denmark)

    Hinge, Mogens; Cecatto, Marcel; Kingshott, Peter;

    2009-01-01

    Chromium surfaces can be electrografted with organic surface films using 4-nitro- or 4-fluorobenzenediazonium salts, despite the fact that the surfaces are covered with a protective chromium oxide layer...

  17. FORMATION AND DESTRUCTION OF HEXAVALENT CHROMIUM IN A LABORATORY SWIRL FLAME INCINERATOR

    Science.gov (United States)

    The partitioning of chromium (Cr) in combustion systems was investigated theoretically and experimentally. Theoretical predictions were based on chemical equilibrium and suggested that hexavalent chromium [Cr(VI)] was favored by the presence of chlorine (Cl) and diminished by the...

  18. Effective bioleaching of chromium in tannery sludge with an enriched sulfur-oxidizing bacterial community.

    Science.gov (United States)

    Zeng, Jing; Gou, Min; Tang, Yue-Qin; Li, Guo-Ying; Sun, Zhao-Yong; Kida, Kenji

    2016-10-01

    In this study, a sulfur-oxidizing community was enriched from activated sludge generated in tannery wastewater treatment plants. Bioleaching of tannery sludge containing 0.9-1.2% chromium was investigated to evaluate the effectiveness of the enriched community, the effect of chromium binding forms on bioleaching efficiency, and the dominant microbes contributing to chromium bioleaching. Sludge samples inoculated with the enriched community presented 79.9-96.8% of chromium leaching efficiencies, much higher than those without the enriched community. High bioleaching efficiencies of over 95% were achieved for chromium in reducible fraction, while 60.9-97.9% were observed for chromium in oxidizable and residual fractions. Acidithiobacillus thiooxidans, the predominant bacteria in the enriched community, played an important role in bioleaching, whereas some indigenous heterotrophic species in sludge might have had a supporting role. The results indicated that A. thiooxidans-dominant enriched microbial community had high chromium bioleaching efficiency, and chromium binding forms affected the bioleaching performance.

  19. CHROMIUM ELECTROANALYSIS AT SCREEN PRINTED ELECTRODE MODIFIED BY THIN FILMS OF NICKEL

    Science.gov (United States)

    A rapid and potentially cost-effective electrochemical method is reported for analysis of chromium (VI) and Chromium(III) using a nickel modified screen printed carbon ink electrode. Electrochemical characteristics of nickel modified electrode as well voltammetric behavior f...

  20. p53 isoforms, Δ133p53 and p53β, are endogenous regulators of replicative cellular senescence

    OpenAIRE

    Fujita, Kaori; Mondal, Abdul M.; Horikawa, Izumi; Nguyen, Giang H.; Kumamoto, Kensuke; Sohn, Jane J.; Bowman, Elise D.; Mathe, Ewy A.; Schetter, Aaron J.; Pine, Sharon R.; Ji, Helen; Vojtesek, Borivoj; Bourdon, Jean-Christophe; Lane, David P; Harris, Curtis C.

    2009-01-01

    The finite proliferative potential of normal human cells leads to replicative cellular senescence, which is a critical barrier to tumour progression in vivo1–3. We show that human p53 isoforms (Δ133p53 and p53β)4 constitute an endogenous regulatory mechanism for p53-mediated replicative senescence. Induced p53β and diminished Δ133p53 were associated with replicative senescence, but not oncogene-induced senescence, in normal human fibroblasts. The replicatively senescent fibroblasts also expre...

  1. Processes controlling the chromium isotopic composition of river water: Constraints from basaltic river catchments

    Science.gov (United States)

    D'Arcy, Joan; Babechuk, Michael G.; Døssing, Lasse Nørbye; Gaucher, Claudio; Frei, Robert

    2016-08-01

    We report chromium (Cr) isotope compositions and concentrations (and additional geochemical and physicochemical data) of bedrock, soils and river waters from two geographically distinct basaltic river catchments, the Uruguay River catchment (Uruguay) and the Glenariff River catchment (Northern Ireland, United Kingdom), to investigate the processes that control Cr mobilisation and fractionation during weathering and riverine transport to the sea. Our results show that the Cr isotope compositions of soils are a function of the modal abundance and weathering rates of Cr-bearing minerals. The accumulation of weathering resistant Cr-spinels in the soils of Northern Ireland results in soils which are enriched in Cr and have δ53Cr values within the range of local bedrock (δ53Cr value of -0.21 ± 0.12‰, 2σ, n = 4). By contrast, the more easily weathered Cr-silicates in the bedrock of Uruguay results in greater Cr loss from the soil and a depletion in the heavy isotopes of Cr (with average δ53Cr value of -0.32 ± 0.04‰, 2σ, n = 4) relative to the local bedrock (δ53Cr value of -0.22 ± 0.08‰, 2σ, n = 4). The river waters in both catchments are predominantly enriched in the heavy 53Cr isotope relative to bedrock, although the range and average river water δ53Cr values differ significantly between each. The Uruguay rivers exhibit a restricted range in δ53Cr values, with a mean of +0.08 ± 0.06‰ (2σ, n = 5) that represents a positive fractionation of +0.2‰ relative to bedrock, and is best explained by the unidirectional formation of Cr(VI) during weathering that has not been significantly modified by back-reduction to Cr(III). By contrast, the Glenariff stream and river waters (Northern Ireland) exhibit a wide range in δ53Cr values from -0.17 ± 0.3‰ (2σ, n = 4) to +1.68 ± 0.3‰ (n = 1) that appears to reflect the variable redox conditions of the catchment. In general, the values with the lowest 53Cr enrichment have higher Cr concentrations, the lowest

  2. STS-53 Launch and Landing

    Science.gov (United States)

    1992-01-01

    Footage of various stages of the STS-53 Discovery launch is shown, including shots of the crew at breakfast, getting suited up, and departing to board the Orbiter. The launch is seen from many vantage points, as is the landing. On-orbit activities show the crew performing several medical experiments, such as taking a picture of the retina and measuring the pressure on the eyeball. One crewmember demonstrates how to use the rowing machine in an antigravity environment.

  3. Chromium isotopes in siliciclastic sediments and sedimentary rocks as a proxy for Earth surface redox

    Science.gov (United States)

    Reinhard, C. T.; Planavsky, N. J.; Wang, X.; Owens, J. D.; Johnson, T. M.; Fischer, W. W.; Lyons, T. W.

    2013-12-01

    Chromium (Cr) isotopes are an emerging and potentially promising proxy for tracking redox processes at Earth's surface. However, recent efforts to reconstruct the Cr isotope record through time have primarily focused on sporadically deposited iron-rich chemical sediments, with large temporal gaps and limited capacity to explore the Cr isotope record relative to modern and recent marine processes. However, the basic inorganic chemistry of Cr suggests that anoxic marine basins factor prominently in the global Cr cycle, and that likewise sediments deposited within anoxic basins may offer an unexplored Cr isotope archive throughout Earth's history. We present authigenic δ53Cr data from sediments of the Cariaco Basin, Venezuela--a ';type' environment on the modern Earth for large, perennially anoxic basins with relatively strong hydrological connections to the global ocean. Combined with currently available constraints on the δ53Cr composition of modern Atlantic seawater, these data are consistent with the hypothesis that anoxic marine basins can serve as a chemical archive of the first-order features of seawater δ53Cr variation. We employ a simple quantitative model to explore the implications of this hypothesis for global Cr isotope mass balance and the possible utility of authigenic δ53Cr in anoxically deposited siliciclastic sediments and sedimentary rocks as a global paleoredox proxy. Our focus is a basic analysis of the primary controls on seawater δ53Cr as related to both the marine redox landscape and the processes involved in the weathering and aqueous-particulate transport of Cr at Earth's surface. As a case study, we provide analysis of new bulk δ53Cr data through a Cretaceous Oceanic Anoxic Event (OAE-2), which shows a well-defined ~1.0‰ negative excursion during the event coupled with evidence for a drawdown of the marine Cr reservoir. We present a conceptual model to explain these observations, and interpret this shift to suggest a shutdown of

  4. Scientific Opinion on chromium(III lactate tri-hydrate as a source of chromium added for nutritional purposes to foodstuff

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS

    2012-10-01

    Full Text Available

    The Panel on Food Additives and Nutrient Sources added to Food provides a scientific opinion on the safety and bioavailability of chromium(III lactate tri-hydrate as a source of chromium(III added for nutritional purposes to foodstuffs. The safety of chromium itself, in terms of the amounts that may be consumed, is outside the remit of this Panel. No new data have been provided as regards the safety and bioavailability of chromium from chromium(III lactate tri-hydrate. The Panel concurs with its earlier views stating that no evidence was provided supporting the bioavailability of chromium from chromium(III lactate tri-hydrate. Chromium(III lactate tri-hydrate is claimed to be freely soluble in water, however, chromium(III lactate tri-hydrate exists as a weak complex that may influence the bioavailability of chromium(III in the gastrointestinal tract. The Panel re-iterates that because of the complex chemistry of chromium(III lactate tri-hydrate in aqueous solutions and its limited solubility at pH >5, the bioavailability of chromium(III from chromium(III lactate tri-hydrate is low. Based on a conservative exposure estimate, the Panel calculated the combined intake of chromium(III from supplements and from foods fortified with chromium(III lactate tri-hydrate, for both adults and children, to be approximately 240 μg chromium(III/day, which is below the value of 250 µg/day established by the WHO for supplemental intake of chromium that should not be exceeded. The Panel noted that the use of chromium(III lactate tri-hydrate in the form of a premix with lactose, added to foods, would result in an exposure at the mean for adults of approximately 7-37 mg lactose/day (0.12-0.62 μg lactose/kg bw/day and to 36-192 μg lactate/day (0.60-3.20 μg/kg bw/day. Given that subjects with lactose maldigestion will tolerate up to 12 g of lactose with no or minor symptoms, these levels are not of safety concern.

  5. Biosorption of hexavalent chromium in a tannery industry wastewater using fungi species

    OpenAIRE

    Sivakumar, D.

    2016-01-01

    The isolated fungi species of different kinds from chromium contaminated soil sites located in Nagalkeni, Chennai were used for reducing chromium(VI) in a tannery industry wastewater of Nagalkeni, Chennai.  The experiments were conducted to know biosorption potential of isolated fungi species for removing chromium(VI) in a tannery industry wastewater against the different pH, fungi biomass and chromium(VI) concentration (dilution ratio).  The results of this study indicated that the order of ...

  6. Investigation of hexavalent chromium removal from Synthetic wastewater by using Peaganum

    OpenAIRE

    Ali Akbar Taghizadeh; Maryam khodadadi; Taher Shahriary; Hadighe Dorri; mahla zaferanieh; rasoul khosravi

    2012-01-01

    Background and Aim: Discharge of industrial wastewater containing hexavalent chromium into the environment can have harmful effects to the types of organisms. So, chromium should remove before discharging to the environment with an effective method. The purpose of this study of is hexavalent chromium removed with Peganum harmala granular seeds(PGS).   Materials and Methods: In this experimental study, The removal of hexavalent chromium with using PGS, with changes in time, pH, adsorbent dose,...

  7. Influence of chromium, oxygen, carbon and nitrogen on iron viscosity

    International Nuclear Information System (INIS)

    Kinetic viscosity of 70 beforehand melted iron samples with additions of chromium (up to 2%) and carbon (up to 1%) has been investigated. Different conditions of melting brought about differences in oxygen and nitrogen contents. Viscosity of most samples has been determined in the 1550-1650 deg C temperature range. It is stated that small additions to pure iron of each of the investigated elements (O, Cr, C, N) decrease its viscosity. Combined effect of these additions on viscosity is inadditive. Simultaneous introduction of oxygen and carbon may result in increase of melt viscosity. The same fact is observed at combined introduction of chromium and nitrogen. Simultaneous introduction of other impurities-chromium with oxygen or carbon, nitrogen with oxygen causes amplification of their individual effect. Reasons for the observed regularities result from changes in energies of interparticle interactions in the melt and therefore rebuilding of structure of its short-range order

  8. A study of the process of desorption of hexavalent chromium

    Directory of Open Access Journals (Sweden)

    W.B. Amorim

    2003-09-01

    Full Text Available In this work the process of desorption of hexavalent chromium, a toxic metal ion, from the marine algae Sargassum sp, following biosorption experiments 2³ factorial design was studied. A technique was applied to three eluents: HCl, H2SO4 and EDTA. Three factors of importance were evaluated: concentration of eluent, the ratio between mass of biosorbent and volume of eluent (S/L and process time. A statistical analysis of the experimental results showed that the three variables evaluated are significant for all three eluents. The models for chromium desorption were validated, as the results agreed well with the observed values. Through use of the response surface methodology, a factorial design based optimization technique; it was possible to identify the most suitable eluent and the interval of values for the process variables that resulted in the most significant desorption of chromium, which is relevant information for work aiming at process optimization.

  9. Structural and magnetic properties of chromium doped zinc ferrite

    International Nuclear Information System (INIS)

    Zinc chromium ferrites with chemical formula ZnCrxFe2−xO4 (x = 0.0, 0.2, 0.4, 0.6, 0.8, 1.0) were prepared by Sol - Gel technique. The structural as well as magnetic properties of the synthesized samples have been studied and reported here. The structural characterizations of the samples were analyzed by using X – Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscope (SEM), and Transmission Electron Microscope (TEM). The single phase spinel cubic structure of all the prepared samples was tested by XRD and FTIR. The particle size was observed to decrease from 18.636 nm to 6.125 nm by chromium doping and induced a tensile strain in all the zinc chromium mixed ferrites. The magnetic properties of few samples (x = 0.0, 0.4, 1.0) were investigated using Vibrating Sample Magnetometer (VSM)

  10. Chromium Resistant Bacteria: Impact on Plant Growth in Soil Microcosm

    Directory of Open Access Journals (Sweden)

    Sayel Hanane

    2014-07-01

    Full Text Available Three chromium resistant bacterial strains, Pseudomonas fluorescens PF28, Enterobacter amnigenus EA31 and Enterococcus gallinarum S34 isolated from tannery waste contaminated soil were used in this study. All strains could resist a high concentration of K2Cr2O7 that is up to 300 mg/L. The effect of these strains on clover plants (Trifolium campestre in the presence of two chromium salts CrCl3 and K2Cr2O7 was studied in soil microcosm. Application of chromium salts adversely affected seed germination, root and shoot length. Bacterial inoculation improved the growth parameters under chromate stress when compared with non inoculated respective controls. There was observed more than 50% reduction of Cr(VI in inoculated soil microcosms, as compared to the uninoculated soil under the same conditions. The results obtained in this study are significant for the bioremediation of chromate pollution.

  11. Electron magnetic resonance investigation of chromium diffusion in yttria powders

    Energy Technology Data Exchange (ETDEWEB)

    Biasi, R.S. de, E-mail: rsbiasi@ime.eb.b [Secao de Engenharia Mecanica e de Materiais, Instituto Militar de Engenharia, Pr. General Tiburcio, 80, 22290-270 Rio de Janeiro, RJ (Brazil); Grillo, M.L.N., E-mail: mluciag@uerj.b [Instituto de Fisica, Universidade do Estado do Rio de Janeiro, 20550-013 Rio de Janeiro, RJ (Brazil)

    2010-03-01

    The electron magnetic resonance (EMR) technique was used to investigate the diffusion of chromium in yttria (Y{sub 2}O{sub 3}) powders. The EMR absorption intensity was measured for several annealing times and three different temperatures of isothermal annealing: 1273, 1323 and 1373 K. The activation temperature for diffusion, calculated from the experimental data using a theoretical model based on the Fick equation, was found to be E{sub A}=342+-5 kJ mol{sup -1}. This value is larger than the activation energy for the diffusion of chromium in rutile (TiO{sub 2}), periclase (MgO) and cobalt monoxide (CoO) and smaller than the activation energy for the diffusion of chromium in chrysoberyl (BeAl{sub 2}O{sub 4}).

  12. Chromium accumulation by the hyperaccumulator plant Leersia hexandra Swartz.

    Science.gov (United States)

    Zhang, Xue-Hong; Liu, Jie; Huang, Hai-Tao; Chen, Jun; Zhu, Yi-Nian; Wang, Dun-Qiu

    2007-04-01

    Leersia hexandra Swartz (Gramineae), which occurs in Southern China, has been found to be a new chromium hyperaccumulator by means of field survey and pot-culture experiment. The field survey showed that this species had an extraordinary accumulation capacity for chromium. The maximum Cr concentration in the dry leaf matter was 2978 mg kg(-1) on the side of a pond near an electroplating factory. The average concentration of chromium in the leaves was 18.86 times as that in the pond sediment, and 297.41 times as that in the pond water. Under conditions of the nutrient solution culture, it was found that L. hexandra had a high tolerance and accumulation capacity to Cr(III) and Cr(VI). Under 60 mg l(-1) Cr(III) and 10 mg l(-1) Cr(VI) treatment, there was no significant decrease of biomass in the leaves of L. hexandra (p>0.05). The highest bioaccumulation coefficients of the leaves for Cr(III) and Cr(VI) were 486.8 and 72.1, respectively. However, L. hexandra had a higher accumulation capacity for Cr(III) than for Cr(VI). At the Cr(III) concentration of 10 mg l(-1) in the culture solution, the concentration of chromium in leaves was 4868 mg kg(-1), while at the same Cr(VI) concentration, the concentration of chromium in leaves was only 597 mg kg(-1). These results confirmed that L. hexandra is a chromium hyperaccumulator which grows rapidly with a great tolerance to Cr and broad ecological amplitude. This species could provide a new plant resource that explores the mechanism of Cr hyperaccumulation, and has potential for usage in the phytoremediation of Cr-contaminated soil and water. PMID:17207838

  13. 21 CFR 73.3110a - Chromium-cobalt-aluminum oxide.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Chromium-cobalt-aluminum oxide. 73.3110a Section... LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Medical Devices § 73.3110a Chromium-cobalt-aluminum oxide. (a) Identity. The color additive chromium-cobalt-aluminum oxide (Pigment Blue 36) (CAS Reg....

  14. 75 FR 60454 - Draft Toxicological Review of Hexavalent Chromium: In Support of Summary Information on the...

    Science.gov (United States)

    2010-09-30

    ... AGENCY Draft Toxicological Review of Hexavalent Chromium: In Support of Summary Information on the..., ``Toxicological Review of Hexavalent Chromium: In Support of Summary Information on the Integrated Risk..., 2010. The listening session on the draft assessment for hexavalent chromium will be held on November...

  15. 76 FR 20349 - Draft Toxicological Review of Hexavalent Chromium: In Support of Summary Information on the...

    Science.gov (United States)

    2011-04-12

    ... AGENCY Draft Toxicological Review of Hexavalent Chromium: In Support of Summary Information on the..., ``Toxicological Review of Hexavalent Chromium: In Support of Summary Information on the Integrated Risk... workshop on the draft assessment for Hexavalent Chromium will be held on May 12, 2011, beginning at 8:30...

  16. 77 FR 61431 - Hexavalent Chromium Standards; Extension of the Office of Management and Budget's (OMB) Approval...

    Science.gov (United States)

    2012-10-09

    ... Occupational Safety and Health Administration Hexavalent Chromium Standards; Extension of the Office of...) approval of the information collection requirements specified in the Hexavalent Chromium Standards for... requirements specified in the Hexavalent Chromium (Cr(VI)) Standards for General Industry (29 CFR...

  17. Speciation dependent radiotracer studies on chromium preconcentration using iron doped calcium alginate biopolymer

    International Nuclear Information System (INIS)

    The work aims to study the differential attitude of Ca-alginate (CA) and Fe-doped calcium alginate (Fe-CA) and towards Cr(III) and Cr (IV) so that, depending on the oxidation state of chromium effluent, environmentally sustainable methodologies can be prescribed for removal of chromium. Throughout the experiment 51Cr has been used as the precursor of stable chromium

  18. Evaluation of flexural bond strength of porcelain to used nickel-chromium alloy in various percentages

    Directory of Open Access Journals (Sweden)

    VNV Madhav

    2012-01-01

    Fresh nickel-chromium alloy shows the greatest porcelain adherence.There is no significant change in bond strength of ceramic to alloy with up to 75% of used nickel-chromium alloy.At least 25%- of new alloy should be added when recycled nickel-chromium alloy is being used for metal ceramic restorations.

  19. Wild-type p53 binds to MYC promoter G-quadruplex

    Science.gov (United States)

    Petr, Marek; Helma, Robert; Polášková, Alena; Krejčí, Aneta; Dvořáková, Zuzana; Kejnovská, Iva; Navrátilová, Lucie; Adámik, Matej; Vorlíčková, Michaela; Brázdová, Marie

    2016-01-01

    G-quadruplexes are four-stranded nucleic acid structures that are implicated in the regulation of transcription, translation and replication. Genome regions enriched in putative G-quadruplex motifs include telomeres and gene promoters. Tumour suppressor p53 plays a critical role in regulatory pathways leading to cell cycle arrest, DNA repair and apoptosis. In addition to transcriptional regulation mediated via sequence-specific DNA binding, p53 can selectively bind various non-B DNA structures. In the present study, wild-type p53 (wtp53) binding to G-quadruplex formed by MYC promoter nuclease hypersensitive element (NHE) III1 region was investigated. Wtp53 binding to MYC G-quadruplex is comparable to interaction with specific p53 consensus sequence (p53CON). Apart from the full-length wtp53, its isolated C-terminal region (aa 320–393) as well, is capable of high-affinity MYC G-quadruplex binding, suggesting its critical role in this type of interaction. Moreover, wtp53 binds to MYC promoter region containing putative G-quadruplex motif in two wtp53-expressing cell lines. The results suggest that wtp53 binding to G-quadruplexes can take part in transcriptional regulation of its target genes. PMID:27634752

  20. Fertilizers and Mixed Crop Cultivation of Chromium Tolerant and Sensitive Plants under Chromium Toxicity.

    Science.gov (United States)

    Dheeba, B; Sampathkumar, P; Kannan, K

    2015-01-01

    Zea mays (maize) and Vigna radiata (green gram) are found to be the chromium (Cr) tolerant and sensitive plants, respectively. In the present paper, we investigate the reduction of the toxicity of Cr in the sensitive plants by the mixed crop cultivation in the field using various amendments. Further, the potassium dichromate was used as the source of hexavalent Cr. The results indicated that Cr adversely affects both the growth and yield of plants. The soil properties vary with Cr and different fertilizer amendments and the yield of both plants were affected by Cr. We conclude that metal accumulation of seeds of green gram was higher than corn and the application of single fertilizer either farm yard manure (FYM) or nitrogen, phosphorous, and potassium (NPK) enhances the growth and yield of both the tolerant and sensitive plants in the mixed crop cultivations. PMID:25709647

  1. Urinary levels of nickel and chromium associated with dental restoration by nickel-chromium based alloys.

    Science.gov (United States)

    Chen, Bo; Xia, Gang; Cao, Xin-Ming; Wang, Jue; Xu, Bi-Yao; Huang, Pu; Chen, Yue; Jiang, Qing-Wu

    2013-03-01

    This paper aims to investigate if the dental restoration of nickel-chromium based alloy (Ni-Cr) leads to the enhanced excretions of Ni and Cr in urine. Seven hundred and ninety-five patients in a dental hospital had single or multiple Ni-Cr alloy restoration recently and 198 controls were recruited to collect information on dental restoration by questionnaire and clinical examination. Urinary concentrations of Ni and Cr from each subject were measure by graphite furnace atomic absorption spectrometry. Compared to the control group, the urinary level of Ni was significantly higher in the patient group of dental restoration. Potential short- and long-term effects of Ni-Cr alloy restoration need to be investigated.

  2. Primary and secondary crystallization of modified hypoeutectic chromium cast iron

    Directory of Open Access Journals (Sweden)

    A. Studnicki

    2010-04-01

    Full Text Available The paper presents investigations of crystallization of modified hypoeutectic wear resistant chromium cast iron which contains carbon about 2% and chromium on three levels (12%, 18% and 25%. Three substances were applied to the modification ( boron carbide (B4C, ferroniobium (FeNb and mixture of ferroniobium and mischmetal (RE. The investigations of crystallization were conducted the DTA method in DTA-C and DTA-Is testers. The influence on the course of the process of primary and secondary crystallization was observed.

  3. Use of chitosan for chromium removal from exhausted tanning baths.

    Science.gov (United States)

    Cesaro, Raffaele; Fabbricino, Massimiliano; Lanzetta, Rosa; Mancino, Anna; Naviglio, Biagio; Parrilli, Michelangelo; Sartorio, Roberto; Tomaselli, Michele; Tortora, Gelsomina

    2008-01-01

    A novel approach, based on chitosan heavy-metal sequestrating ability, is proposed for chromium(III) removal from spent tanning liquor. Experimental results, obtained at lab-scale using real wastewater, are presented and discussed. Resulting efficiencies are extremely high, and strongly dependent on chitosan dose and pH value. Comparative analyses with other polysaccharides is also carried out showing that amine groups are more efficient than carboxyl and sulphate ones. Chromium recovery from sorption complexes and chitosan regeneration is finally proposed to optimize the whole process.

  4. Concentration profiles and electrochemical properties of chromium and nickel implanted iron

    International Nuclear Information System (INIS)

    The concentration profiles of chromium and nickel implanted in pure iron were measured with a secondary ion mass analyzer. The electrochemical properties of implanted iron were investigated by means of a cyclic voltammetry in 0.5 M acetate buffer solution (pH = 5.0 +- 0.1). Chromium, nickel and argon ion implantations have been carried out with doses of 1 x 1016 -- 1 x 1017 ions/cm2 at an energy of 150 keV. The target temperature during ion implantation rised to --1800C from room temperature by the heating effect of ion beam itself. The profile of Cr implanted in pure iron has two peaks; the first peak near the surface and the second peak near the depth predicted by the range theory. However, the first peak was not found in the specimen 1 st-implanted with Ni. The electrochemical properties of Cr implanted iron approach to that of Fe-18% Cr bulk alloy (SUS 430), as the dose increases. The polarization curve of Cr implanted iron with 1 x 1017 ions/cm2 is almost the same as that of SUS 430. The polarization curve of Ni and Cr implanted iron is similar to that of Fe-18%Cr-8%Ni bulk alloy (SUS 304) after annealing at --3000C for 20 min. These results show that Cr and Ni implanted surface layer is useful for the improvement of corrosion resistance of iron. (author)

  5. Inhibition of GSK3B bypass drug resistance of p53-null colon carcinomas by enabling necroptosis in response to chemotherapy

    DEFF Research Database (Denmark)

    Grassilli, Emanuela; Narloch, Robert; Federzoni, Elena;

    2013-01-01

    Evasion from chemotherapy-induced apoptosis due to p53 loss strongly contributes to drug resistance. Identification of specific targets for the treatment of drug-resistant p53-null tumors would therefore increase the effectiveness of cancer therapy.......Evasion from chemotherapy-induced apoptosis due to p53 loss strongly contributes to drug resistance. Identification of specific targets for the treatment of drug-resistant p53-null tumors would therefore increase the effectiveness of cancer therapy....

  6. The isotopic composition of authigenic chromium in anoxic marine sediments: A case study from the Cariaco Basin

    Science.gov (United States)

    Reinhard, Christopher T.; Planavsky, Noah J.; Wang, Xiangli; Fischer, Woodward W.; Johnson, Thomas M.; Lyons, Timothy W.

    2014-12-01

    Chromium (Cr) isotopes are an emerging proxy for tracking redox processes at the Earth's surface. However, there has been limited exploration of the Cr isotope record of modern and recent marine sediments. The basic inorganic chemistry of Cr suggests that anoxic marine basins should factor prominently in the global Cr cycle and that sediments deposited within anoxic basins may offer a valuable Cr isotope archive throughout Earth's history. Here, we present δ53Cr data from sediments of the Cariaco Basin, Venezuela-a 'type' environment for large, perennially anoxic basins with a relatively strong hydrological connection to the global oceans. We document a marked positive shift in bulk δ53Cr values following the termination of the Last Glacial Maximum, followed by relative stasis. Based on a suite of independent redox proxies, this transition marks a switch from oxic to persistently anoxic and sulfidic (euxinic) depositional conditions within the basin. We find good agreement between two independent approaches toward estimating the δ53Cr composition of authigenic Cr in euxinic Cariaco Basin sediments and that these estimates are very similar to the δ53Cr composition of modern open Atlantic Ocean seawater. These data, together with considerations of reaction kinetics and mass balance within the Cariaco Basin, are consistent with the hypothesis that anoxic marine settings can serve as a chemical archive of first-order trends in seawater δ53Cr composition. Additionally, the Cariaco Basin data suggest that there has been secular stability in the average δ53Cr value of Atlantic seawater over the last ∼15 kyr.

  7. microRNAs与TP53基因调控网络研究进展%Advances in microRNAs and TP53 Gene Regulatory Network

    Institute of Scientific and Technical Information of China (English)

    龚朝建; 黄宏斌; 徐柯; 梁芳; 李小玲; 熊炜; 曾朝阳; 李桂源

    2012-01-01

    TP53基因(编码p53蛋白)作为一个重要的抑瘤基因,通过调控一系列信号转导通路广泛参与了多种恶性肿瘤的发生发展,一直是肿瘤分子生物学研究领域的热点.最近的研究发现,microRNAs(miRNAs)参与了TP53的信号通路,它们之间存在着复杂的调控网络.一方面,p53通过调控一些miRNAs的转录及转录后成熟,促进细胞周期阻滞、诱导细胞凋亡和衰老,抑制肿瘤发生.另一方面,许多miRNAs,如miR-25、miR-30d、miR-125b和miR-504等可直接调控p53的表达与活性,参与TP53信号通路的调节,还有一些miRNAs则通过调节p53上下游基因,发挥重要的生物学功能.其中,最具有代表性的是miR-34家族,它们受p53直接调控并参与TP53信号通路,通过靶向抑制多个TP53信号通路关键分子的表达,发挥抑瘤作用.此外,它们还可以通过抑制沉默信息调节子,增强p53的活性,反馈调节TP53信号通路.miRNAs与TP53之间调控网络的研究,是对TP53抑瘤机制的重要补充.%The tumor suppressor TP53 gene, which encodes p53 protein, is a hotspot of all time in molecular oncology. p53 suppresses tumor initiation and progression through its regulation of many downstream genes. Recent studies have revealed that microRNAs (miRNAs) interact with the p53 pathway and form a complex regulatory network. On one hand, p53 promotes cell cycle arrest and induces cell apoptosis and senescence to suppress tumorigenesis by regulating the transcription and post-transcriptional maturation of multiple miRNAs. On the other hand, many miRNAs fine-tune the p53 pathway through regulation of TP53 and its upstream regulators or downstream effectors. The miR-34s family, directly transactivated by p53 represents a large number of p53-regulated miRNAs. They exert their tumor suppressing function via targeted inhibition of multiple key molecules in the p53 pathway. Furthermore, miR-34s enhance p53 activity through a feedback loop by inhibiting silent

  8. NEK9-dependent proliferation of cancer cells lacking functional p53

    OpenAIRE

    Daisuke Kurioka; Fumitaka Takeshita; Koji Tsuta; Hiromi Sakamoto; Shun-ichi Watanabe; Kenji Matsumoto; Masatoshi Watanabe; Hitoshi Nakagama; Takahiro Ochiya; Jun Yokota; Takashi Kohno; Naoto Tsuchiya

    2014-01-01

    Dysfunction of the p53 network is a major cause of cancer development, and selective elimination of p53-inactivated cancer cells therefore represents an ideal therapeutic strategy. In this study, we performed a microRNA target screen that identified NEK9 (NIMA-related kinase 9) as a crucial regulator of cell-cycle progression in p53-inactivated cancer cells. NEK9 depletion selectively inhibited proliferation in p53-deficient cancer cells both in vitro and in vivo. The resultant cell-cycle arr...

  9. p53 gene mutations, p53 protein accumulation and compartmentalization in colorectal adenocarcinoma.

    OpenAIRE

    Bosari, S.; Viale, G.; Roncalli, M; Graziani, D.; Borsani, G; Lee, A. K.; Coggi, G.

    1995-01-01

    p53 accumulation may occur in the nucleus and/or cytoplasm of neoplastic cells. Cytoplasmic accumulation has been reported to be an unfavorable, but not established, prognostic indicator in colorectal cancer. Different types of p53 intracellular compartmentalization could depend either on p53 gene mutations or on the interaction with p53 protein ligands. The purposes of our study were (1) to assess whether the different patterns of p53 accumulation are selectively associated with p53 mutation...

  10. Conversion of Fibroblasts to Neural Cells by p53 Depletion

    Directory of Open Access Journals (Sweden)

    Di Zhou

    2014-12-01

    Full Text Available Conversion from fibroblasts to neurons has recently been successfully induced. However, the underlying mechanisms are poorly understood. Here, we find that depletion of p53 alone converts fibroblasts into all three major neural lineages. The induced neuronal cells express multiple neuron-specific proteins and generate action potentials and transmitter-receptor-mediated currents. Surprisingly, depletion does not affect the well-known tumorigenic p53 target, p21. Instead, knockdown of p53 upregulates neurogenic transcription factors, which in turn boosts fibroblast-neuron conversion. p53 binds the promoter of the neurogenic transcription factor Neurod2 and regulates its expression during fibroblast-neuron conversion. Furthermore, our method provides a high efficiency of conversion in late-passage fibroblasts. Genome-wide transcriptional analysis shows that the p53-deficiency-induced neurons exhibit an expression profile different from parental fibroblasts and similar to control-induced neurons. The results may help to understand and improve neural conversion mechanisms to develop robust neuron-replacement therapy strategies.

  11. Constant rate of p53 tetramerization in response to DNA damage controls the p53 response

    OpenAIRE

    Gaglia, Giorgio; Lahav, Galit

    2014-01-01

    The dynamics of the tumor suppressor protein p53 have been previously investigated in single cells using fluorescently tagged p53. Such approach reports on the total abundance of p53 but does not provide a measure for functional p53. We used fluorescent protein-fragment complementation assay (PCA) to quantify in single cells the dynamics of p53 tetramers, the functional units of p53. We found that while total p53 increases proportionally to the input strength, p53 tetramers are formed in cell...

  12. hSSB1 regulates both the stability and the transcriptional activity of p53

    Institute of Scientific and Technical Information of China (English)

    Shuangbing Xu; Yuanzhong Wu; Qiong Chen; Jingying Cao; Kaishun Hu; Jianjun Tang; Yi Sang

    2013-01-01

    The tumor suppressor p53 is essential for several cellular processes that are involved in the response to diverse genotoxic stress,including cell cycle arrest,DNA repair,apoptosis and senescence.Studies of the regulation of p53 have mostly focused on its stability and transactivation; however,new regulatory molecules for p53 have also been frequently identified.Here,we report that human ssDNA binding protein SSB1 (hSSB1),a novel DNA damageassociated protein,can interact with p53 and protect p53 from ubiquitin-mediated degradation.Furthermore,hSSB1 also associates with the acetyltransferase p300 and is required for efficient transcriptional activation of the p53 target gene p21 by affecting the acetylation of p53 at lysine382.Functionally,the hSSB1 knockdown-induced abrogation of the G2/M checkpoint is partially dependent on p53 or p300.Collectively,our results indicate that hSSB1 may regulate DNA damage checkpoints by positively modulating p53 and its downstream target p21.

  13. Pharmacological activation of wild-type p53 in the therapy of leukemia.

    Science.gov (United States)

    Kojima, Kensuke; Ishizawa, Jo; Andreeff, Michael

    2016-09-01

    The tumor suppressor p53 is inactivated by mutations in the majority of human solid tumors. Conversely, p53 mutations are rare in leukemias and are only observed in a small fraction of the patient population, predominately in patients with complex karyotype acute myeloid leukemia or hypodiploid acute lymphoblastic leukemia. However, the loss of p53 function in leukemic cells is often caused by abnormalities in p53-regulatory proteins, including overexpression of MDM2/MDMX, deletion of CDKN2A/ARF, and alterations in ATM. For example, MDM2 inhibits p53-mediated transcription, promotes its nuclear export, and induces proteasome-dependent degradation. The MDM2 homolog MDMX is another direct regulator of p53 that inhibits p53-mediated transcription. Several small-molecule inhibitors and stapled peptides targeting MDM2 and MDMX have been developed and have recently entered clinical trials. The clinical trial results of the first clinically used MDM2 inhibitor, RG7112, illustrated promising p53 activation and apoptosis induction in leukemia cells as proof of concept. Side effects of RG7112 were most prominent in suppression of thrombopoiesis and gastrointestinal symptoms in leukemia patients. Predictive biomarkers for response to MDM2 inhibitors have been proposed, but they require further validation both in vitro and in vivo so that the accumulated knowledge concerning pathological p53 dysregulation in leukemia and novel molecular-targeted strategies to overcome this dysregulation can be translated safely and efficiently into novel clinical therapeutics.

  14. p53 Represses the Oncogenic Sno-MiR-28 Derived from a SnoRNA.

    Directory of Open Access Journals (Sweden)

    Feng Yu

    Full Text Available p53 is a master tumour repressor that participates in vast regulatory networks, including feedback loops involving microRNAs (miRNAs that regulate p53 and that themselves are direct p53 transcriptional targets. We show here that a group of polycistronic miRNA-like non-coding RNAs derived from small nucleolar RNAs (sno-miRNAs are transcriptionally repressed by p53 through their host gene, SNHG1. The most abundant of these, sno-miR-28, directly targets the p53-stabilizing gene, TAF9B. Collectively, p53, SNHG1, sno-miR-28 and TAF9B form a regulatory loop which affects p53 stability and downstream p53-regulated pathways. In addition, SNHG1, SNORD28 and sno-miR-28 are all significantly upregulated in breast tumours and the overexpression of sno-miR-28 promotes breast epithelial cell proliferation. This research has broadened our knowledge of the crosstalk between small non-coding RNA pathways and roles of sno-miRNAs in p53 regulation.

  15. Pharmacological activation of wild-type p53 in the therapy of leukemia.

    Science.gov (United States)

    Kojima, Kensuke; Ishizawa, Jo; Andreeff, Michael

    2016-09-01

    The tumor suppressor p53 is inactivated by mutations in the majority of human solid tumors. Conversely, p53 mutations are rare in leukemias and are only observed in a small fraction of the patient population, predominately in patients with complex karyotype acute myeloid leukemia or hypodiploid acute lymphoblastic leukemia. However, the loss of p53 function in leukemic cells is often caused by abnormalities in p53-regulatory proteins, including overexpression of MDM2/MDMX, deletion of CDKN2A/ARF, and alterations in ATM. For example, MDM2 inhibits p53-mediated transcription, promotes its nuclear export, and induces proteasome-dependent degradation. The MDM2 homolog MDMX is another direct regulator of p53 that inhibits p53-mediated transcription. Several small-molecule inhibitors and stapled peptides targeting MDM2 and MDMX have been developed and have recently entered clinical trials. The clinical trial results of the first clinically used MDM2 inhibitor, RG7112, illustrated promising p53 activation and apoptosis induction in leukemia cells as proof of concept. Side effects of RG7112 were most prominent in suppression of thrombopoiesis and gastrointestinal symptoms in leukemia patients. Predictive biomarkers for response to MDM2 inhibitors have been proposed, but they require further validation both in vitro and in vivo so that the accumulated knowledge concerning pathological p53 dysregulation in leukemia and novel molecular-targeted strategies to overcome this dysregulation can be translated safely and efficiently into novel clinical therapeutics. PMID:27327543

  16. The combined status of ATM and p53 link tumor development with therapeutic response

    DEFF Research Database (Denmark)

    Jiang, Hai; Reinhardt, H Christian; Bartkova, Jirina;

    2009-01-01

    commonly used by tumors to bypass early neoplastic checkpoints ultimately determine chemotherapeutic response and generate tumor-specific vulnerabilities that can be exploited with targeted therapies. Specifically, evaluation of the combined status of ATM and p53, two commonly mutated tumor suppressor...... genes, can help to predict the clinical response to genotoxic chemotherapies. We show that in p53-deficient settings, suppression of ATM dramatically sensitizes tumors to DNA-damaging chemotherapy, whereas, conversely, in the presence of functional p53, suppression of ATM or its downstream target Chk2...

  17. Non-p53 p53RE binding protein, a human transcription factor functionally analogous to P53

    OpenAIRE

    Zeng, Xiaoya; Levine, Arnold J.; Lu, Hua

    1998-01-01

    The transactivation activity of the p53 tumor suppressor protein is critical for regulating cell growth and apoptosis. We describe the identification of a transcription factor that is functionally similar to p53 and contains the same DNA binding and transcription activities specific for the p53 responsive DNA element (p53RE). This protein was highly purified through chromatography from HeLa cell extracts. The purified protein was able to bind specifically to the p53RE derived from a p21waf1 p...

  18. The oxidation and reduction of chromium of stainless steels in an eletric arc furnace

    Directory of Open Access Journals (Sweden)

    B. Arh

    2011-07-01

    Full Text Available The oxidation of chromium during the elaboration of stainless steels occurs with oxygen in solution blown inthe melt and with oxides in the slag. A higher content of silicon in the furnace charge decreases the extent of oxidation of chromium, however, the efficient reduction of chromium from the slag is of essential importance for a minimal loss of chromium. In this survey, the theory of the oxidation of chromium, its reduction from the slag and the conditions for the formation of foaming slag are discussed.

  19. 28 CFR 32.53 - Review.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Review. 32.53 Section 32.53 Judicial... BENEFIT CLAIMS Director Appeals and Reviews § 32.53 Review. (a) Upon the filing of the approval (under subpart E of this part) of a claim, the Director shall review the same. (b) The Director may review—...

  20. 33 CFR 53.9 - Responsibilities.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Responsibilities. 53.9 Section 53... WHISTLEBLOWER PROTECTION § 53.9 Responsibilities. (a) The Inspector General, Department of Homeland Security... matter. (b) The Board shall, in accordance with its regulations (33 CFR part 52): (1) Consider under 10...

  1. 33 CFR 110.53 - Niantic, Conn.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Niantic, Conn. 110.53 Section 110.53 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.53 Niantic, Conn. Beginning on the shoreline at latitude...

  2. 14 CFR 1260.53 - Incremental funding.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Incremental funding. 1260.53 Section 1260.53 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.53 Incremental funding. Incremental Funding October 2000...

  3. 7 CFR 3430.53 - Program income.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Program income. 3430.53 Section 3430.53 Agriculture...-GENERAL AWARD ADMINISTRATIVE PROVISIONS Post-Award and Closeout § 3430.53 Program income. (a) General... for program income related to projects financed in whole or in part with Federal funds. (b)...

  4. 7 CFR 15a.53 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Recruitment. 15a.53 Section 15a.53 Agriculture Office... Activities Prohibited § 15a.53 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient...

  5. 45 CFR 86.53 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Recruitment. 86.53 Section 86.53 Public Welfare... in Employment in Education Programs or Activities Prohibited § 86.53 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the...

  6. 10 CFR 34.53 - Posting.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Posting. 34.53 Section 34.53 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Radiation Safety Requirements § 34.53 Posting. All areas in which industrial radiography is...

  7. 15 CFR 400.53 - Information.

    Science.gov (United States)

    2010-01-01

    ... information. Disclosure of public information will be governed by 15 CFR part 4. Public information in the... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Information. 400.53 Section 400.53..., Record and Information § 400.53 Information. (a) Request for information. The Board may...

  8. 7 CFR 1794.53 - Environmental report.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Environmental report. 1794.53 Section 1794.53... AGRICULTURE (CONTINUED) ENVIRONMENTAL POLICIES AND PROCEDURES Procedure for Environmental Assessments With Scoping § 1794.53 Environmental report. (a) After scoping procedures have been completed, RUS...

  9. 40 CFR 230.53 - Aesthetics.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Aesthetics. 230.53 Section 230.53... Characteristics § 230.53 Aesthetics. (a) Aesthetics associated with the aquatic ecosystem consist of the perception of beauty by one or a combination of the senses of sight, hearing, touch, and smell. Aesthetics...

  10. 10 CFR 75.53 - Criminal penalties.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Criminal penalties. 75.53 Section 75.53 Energy NUCLEAR... Enforcement § 75.53 Criminal penalties. (a) Section 223 of the Atomic Energy Act of 1954, as amended, provides for criminal sanctions for willful violation of, or conspiracy to violate, any regulation issued...

  11. 47 CFR 53.211 - Audit planning.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Audit planning. 53.211 Section 53.211 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) SPECIAL PROVISIONS CONCERNING BELL OPERATING COMPANIES Separate Affiliate; Safeguards § 53.211 Audit planning....

  12. 9 CFR 3.53 - Primary enclosures.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Primary enclosures. 3.53 Section 3.53... Facilities and Operating Standards § 3.53 Primary enclosures. All primary enclosures for rabbits shall conform to the following requirements: (a) General. (1) Primary enclosures shall be structurally sound...

  13. 14 CFR 460.53 - Security.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Security. 460.53 Section 460.53 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF....53 Security. An operator must implement security requirements to prevent any space flight...

  14. Uncovering the role of p53 splice variants in human malignancy: a clinical perspective

    Directory of Open Access Journals (Sweden)

    Surget S

    2013-12-01

    Full Text Available Sylvanie Surget,1,2 Marie P Khoury,1,2 Jean-Christophe Bourdon1,21Dundee Cancer Centre, 2Jacqui Wood Cancer Centre, Ninewells Hospital, University of Dundee, Dundee, UKAbstract: Thirty-five years of research on p53 gave rise to more than 68,000 articles and reviews, but did not allow the uncovering of all the mysteries that this major tumor suppressor holds. How p53 handles the different signals to decide the appropriate cell fate in response to a stress and its implication in tumorigenesis and cancer progression remains unclear. Nevertheless, the uncovering of p53 isoforms has opened new perspectives in the cancer research field. Indeed, the human TP53 gene encodes not only one but at least twelve p53 protein isoforms, which are produced in normal tissues through alternative initiation of translation, usage of alternative promoters, and alternative splicing. In recent years, it became obvious that the different p53 isoforms play an important role in regulating cell fate in response to different stresses in normal cells by differentially regulating gene expression. In cancer cells, abnormal expression of p53 isoforms contributes actively to cancer formation and progression, regardless of TP53 mutation status. They can also be associated with response to treatment, depending on the cell context. The determination of p53 isoform expression and p53 mutation status helps to define different subtypes within a particular cancer type, which would have different responses to treatment. Thus, the understanding of the regulation of p53 isoform expression and their biological activities in relation to the cellular context would constitute an important step toward the improvement of the diagnostic, prognostic, and predictive values of p53 in cancer treatment. This review aims to summarize the involvement of p53 isoforms in cancer and to highlight novel potential therapeutic targets.Keywords: p53, isoforms, p63, p73, alternative splicing, cancer

  15. Friction and wear behavior of chromium carbide coatings

    International Nuclear Information System (INIS)

    Chromium carbides, tungsten carbide, and chromium oxide have been tested and evaluated as coatings to protect high-temperature gas-cooled reactor (HTGR) steam generator and other HTGR components from adhesion, galling associated with sliding wear or from fretting. Tests were performed in commercially-pure helium and in helium doped with various gaseous impurities (H2, H2O, CH4, CO) to simulate the primary coolant of an HTGR. Several types of chromium carbide coatings including Cr3C2, Cr7C3, and Cr23C6, were tested for wear resistance and resistance to long-term spalling. Tungsten carbide and chromium oxide coatings were tested in sliding wear tests. Cr23C6-NiCr coatings showed the best performance (from 400 to 8160C) whether they were applied by detonation gun or plasma gun spraying methods. The presence of the Cr23C6-NiCr coatings did not affect the creep rupture properties of Alloy 800H substrates at temperatures up to 7600C. Low-cycle fatigue life of similar specimens at 5930C was reduced to 10 to 20% when tested in the 1 to 0.6% strain range

  16. Porosity of detonation coatings on the base of chromium carbide

    International Nuclear Information System (INIS)

    Porosity of detonation coatings on the base of chromium carbide is estimated by the hydrostatic weighing. The open porosity value dependence on the distance of spraying, depth of the charge, ratio and volume of the detonator barrie filing with gas components is established. Pore distribution in the cross section of a specimen tested for porosity is studied by the methods of metallographic analysis

  17. Intestinal absorption of chromium as affected by wheat bran

    Energy Technology Data Exchange (ETDEWEB)

    Keim, K.S.; Holloway, C.L.; Hegsted, M.

    1986-03-01

    This study was designed to investigate the influence of dietary fiber, as found in wheat bran, on the absorption of chromium. Twenty male Sprague-Dawley rats were divided into two groups of 10. The control was fed a semi-purified diet containing casein, methionine, cornstarch, sucrose, corn oil, mineral and vitamin mix, and choline bitartrate. The experimental group was fed the same diet but with soft red winter wheat bran added to a level of 35% of the diet at the expense of sucrose. To determine chromium absorption and uptake by selected tissues, rats were fasted for 24 hr, fed 5 g of the respective diet, 2 hr later intubated with 100..mu..Ci of Cr-51of sacrificed 24 hr later. The rats wee housed in metabolic cages after the Cr-51 intubation. The addition of wheat brand to the diet did not significantly affect chromium absorption as measured by percent dose of Cr-51 in the 24 hr urine. The percent dose in the control group was 0.68 +/- 0.20% (mean +/- SEM) and in the experimental group 0.63 +/- 0.24% (mean +/-SEM) (N.S.). The cr-51 uptake of liver, spleen, jejunum, and blood was not statistically different between groups. These results indicate that dietary fiber as found in wheat bran does not impair intestinal absorption of chromium.

  18. Microbial biotechnology for remediation of aquatic habitats polluted with chromium

    Directory of Open Access Journals (Sweden)

    Viorica Coşier

    2008-12-01

    Full Text Available Chromium may occur in nine different forms of oxidation ranging from ?II to +VI, with forms II, III and VI as the most commonly encountered. In Cluj county, chromium pollution dates well back in time and has caused important dysfunction to the mechanical-biological wastewater purification station of the city of Cluj (Coşier & Diţă 1996. The purpose of this study was to develop one microbial method able to reduce hexavalent chromium (mobile, permeable to cell membrane, carcinogenic and mutagenic (Ishikawa et al 1994 to the trivalent form (insoluble and an essential element for humans (Song et al 2006. Different sources of chromium-reducing bacteria and many sources of carbon and energy added to the Kvasnikov mineral basal medium (Komori et al 1990 with increasing amount of chromate (200- 1000 mg/l were tested. Two bacterial strains, able to reduce even 1000 mg chromate/l, were isolated in pure culture. For one of these bacterial strains, we determined the optimum conditions for the reduction of Cr (VI.

  19. 75 FR 67100 - Superalloy Degassed Chromium From Japan

    Science.gov (United States)

    2010-11-01

    ... superalloy degassed chromium from Japan (70 FR 76030). The Commission is conducting a review to determine..., subparts A, D, E, and F (19 CFR part 207), as most recently amended at 74 FR 2847 (January 16, 2009). \\1... rule 201.15(b)(19 CFR 201.15(b)), 73 FR 24609 (May 5, 2008). This advice was developed in...

  20. 76 FR 8773 - Superalloy Degassed Chromium From Japan

    Science.gov (United States)

    2011-02-15

    ... applicable deadline.'' (75 FR 80457). Accordingly, pursuant to section 751(c) of the Tariff Act of 1930 (19 U... COMMISSION Superalloy Degassed Chromium From Japan AGENCY: United States International Trade Commission... Japan would be likely to lead to continuation or recurrence of material injury. On December 22,...

  1. Intestinal absorption of chromium as affected by wheat bran

    International Nuclear Information System (INIS)

    This study was designed to investigate the influence of dietary fiber, as found in wheat bran, on the absorption of chromium. Twenty male Sprague-Dawley rats were divided into two groups of 10. The control was fed a semi-purified diet containing casein, methionine, cornstarch, sucrose, corn oil, mineral and vitamin mix, and choline bitartrate. The experimental group was fed the same diet but with soft red winter wheat bran added to a level of 35% of the diet at the expense of sucrose. To determine chromium absorption and uptake by selected tissues, rats were fasted for 24 hr, fed 5 g of the respective diet, 2 hr later intubated with 100μCi of Cr-51of sacrificed 24 hr later. The rats wee housed in metabolic cages after the Cr-51 intubation. The addition of wheat brand to the diet did not significantly affect chromium absorption as measured by percent dose of Cr-51 in the 24 hr urine. The percent dose in the control group was 0.68 +/- 0.20% (mean +/- SEM) and in the experimental group 0.63 +/- 0.24% (mean +/-SEM) (N.S.). The cr-51 uptake of liver, spleen, jejunum, and blood was not statistically different between groups. These results indicate that dietary fiber as found in wheat bran does not impair intestinal absorption of chromium

  2. Invariant coefficients of diffusion in iron-chromium-nickel system

    Energy Technology Data Exchange (ETDEWEB)

    Mokrov, A.P.; Akimov, V.K.; Golubev, V.G.

    1984-02-01

    The temperature and concentration dependences of the Dsub(c) coefficients in the ..gamma..-phase of iron-chromium-nickel system are determined. It is proposed to described mutual diffusion in multicomponent systems using invariant, i.e. independent of the choice of solvent, coefficients of diffusion. The assumption that their temperature dependence follows the Arrhenius law is confirmed by the experiment.

  3. Invariant coefficients of diffusion in iron-chromium-nickel system

    International Nuclear Information System (INIS)

    The temperature and concentration dependences of the Dsub(c) coefficients in the γ-phase of iron-chromium-nickel system are determined. It is proposed to described mutual diffusion in mul-- ticomponent systems using invariant, i. e. independent of the choice of solvent, coefficients of diffusion. The assumption that their temperature dependence follows the Arrhenius law is confirmed by the experiment

  4. Differents remediation methodos for lead, chromium and cadmium contaminated soils

    International Nuclear Information System (INIS)

    The usage of phosphates in the remediation of plots contaminated with heavy metals appears to be a good strategy to lessen the danger of these metals. This study analyses the effect of the mobilization of: Lead, chromium and cadmium by utilizing diverse forms of phosphates in contaminated soils of three different origins with ph modification and without it

  5. IRIS TOXICOLOGICAL REVIEW OF HEXAVALENT CHROMIUM (INTERAGENCY SCIENCE CONSULTATION DRAFT)

    Science.gov (United States)

    On Septemeber 30, 2010, the draft Toxicological Review of Hexavalent Chromium and the charge to external peer reviewers were released for external peer review and public comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agenc...

  6. Chromium isotope fractionation during coprecipitation with calcium carbonate

    DEFF Research Database (Denmark)

    Rodler, Alexandra; Sánchez-Pastor, Nuria; Fernández-Díaz, Lurdes;

    The chromium (Cr) isotopic composition of carbonates can potentially be used as a paleoclimate proxy to elucidate past fluctuations of oxygen contents in atmosphere and hydrosphere. The use of Cr isotopes to track paleoenvironmental changes, for example related to the rise of oxygen during...

  7. Fractionation behavior of chromium isotopes during coprecipitation with calcium carbonate

    DEFF Research Database (Denmark)

    Rodler, Alexandra; Sánchez-Pastor, Nuria; Fernández-Díaz, Lurdes;

    2015-01-01

    Interest in chromium (Cr) isotope incorporation into carbonates arises from the observation that Cr isotopic composition of carbonates could be used as a paleoclimate proxy to elucidate past fluctuations of oxygen contents in atmosphere and hydrosphere. The use of Cr isotopes to track...

  8. Discovery of Chromium, Manganese, Nickel, and Copper Isotopes

    OpenAIRE

    Garofali, K.; Robinson, R; Thoennessen, M

    2010-01-01

    Twenty-seven chromium, twenty-five manganese, thirty-one nickel and twenty-six copper isotopes have so far been observed and the discovery of these isotopes is discussed. For each isotope a brief synopsis of the first refereed publication, including the production and identification method, is presented.

  9. Chromium stable isotope fractionation in modern biogeochemical cycling

    DEFF Research Database (Denmark)

    Paulukat, Cora Stefanie

    Chromium (Cr) is, due to its redox-sensitive properties, a powerful tracer for redox processes in environmental studies. Changes in its preferred oxidation state (III and VI) are accompanied by Crisotope fractionation. The Cr-isotope system is a promising tool to reconstruct the evolution of free...

  10. FEATURES OF CHROMIUM DOPING OF WEAR-RESISTANT CAST IRON

    Directory of Open Access Journals (Sweden)

    V. V. Netrebko

    2013-01-01

    Full Text Available The aim of this work analysis of the influence of chromium on the process of carbide formation, changes in chemical composition of the metal substrate in the areas adjacent to the carbides and at the hardness of iron while economy nickel and manganesealloying.

  11. Production performance of quails given chromium organic in ration

    Directory of Open Access Journals (Sweden)

    Deden Sudrajat

    2014-12-01

    Full Text Available Egg production of quails depends on quality of ration. Nutrient manipulation by chromiun inclusion in ration is a possible way to improve production. It is known that chromium mineral in form of GTF in blood has a role not only in enhancement of glucose entering cells through improvement of insulin activity but also in metabolism of lipid and synthesis of protein and elimination of heat stress to improve egg production. This study aimed at assessing egg production of quails fed ration containing chromium-yeast. Sixty-four quails aged 40 days were used. A completely randomized design with 4 treatments and 4 replication was applied in this study. Treatment consisted of commercial ration + Cr 0 ppm (R1, commercial ration + Cr 0.5 ppm (R2, commercial ration + Cr 1 ppm (R3, and commercial ration+ Cr 1.5 ppm (R4. Measurements were taken on feed intake, egg weight, egg mass production, hen day, feed conversion rate, egg index, and egg shell thickness. Results showed that A ration containing organic chromium as much as 1,5 ppm did not affect feed intake, egg production, egg weight, and eggshell thickness, however lowered feed conversion rate by up to 32.25% from that of control. Supplementation of 0,5 ppm chromium in the ration lowered the value of eggs index in the fourth week.

  12. Chromium toxicity to nitrifying bacteria: implications to wastewater treatment

    Science.gov (United States)

    Chromium, a heavy metal that enters wastewater treatment plants (WWTPs) through industrial discharges, can be toxic to microorganisms carrying out important processes within biological wastewater treatment systems. The effect of Cr(III) and Cr(VI) on ammonia dependent specific ox...

  13. DANGER OF HEXAVALENT CHROMIUM AND STRATEGY FOR THE REMEDITATION

    Directory of Open Access Journals (Sweden)

    Aniruddha Roy

    2013-02-01

    Full Text Available Some metals as micronutrients have a major role in the life and growth process of plants and animals. However, certain forms of some metals may also act as toxic material even in relatively small quantities. Chromium is such a metal, whose concentration above a certain limit may cause a serious problem to the health of living organisms. Chromium (Cr may occur in several chemical forms in organic and inorganic systems. In biological systems only Cr (III and Cr (VI are significant. Among these two states, trivalent chromium (Cr-III is considered as an essential component, while hexavalent Chromium (Cr-VI in biological system has been detected as responsible for so many diseases, even some specific forms of cancer. This paper intends to present the adverse effect of Cr(VI on environment as well as on human beings and also try to find a way out to dissolve the problem by a newly developed efficient and cost effective technique.

  14. Effects of chromium picolinate supplementation in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Niladê Rosinski Rocha

    2014-10-01

    Full Text Available The effects of chromium picolinate in Type 2 diabetic patients are investigated.  Seventeen Type 2 diabetic patients were randomly divided into two groups. The experimental group received fiber-rich hypocaloric diet and chromium picolinate whereas the control group received fiber-rich hypocaloric diet and placebo. The chromium picolinate was offered twice a day at the dose of 100 μg. Anthropometric data such as blood pressure, fasting glycemia and glycated hemoglobin (HbA1c were measured and these parameters were evaluated again after 90 days. No difference was reported in rates of body weight, waist, hip, body mass index, blood pressure and fasting glycemia (Control vs. Experimental groups after treatment. However, a decrease (p = 0.0405 of HbA1c occurred in the experimental group when the pre- and post-treatment rates were compared. HbA1c data showed that chromium picolinate improved the glycemic control in Type 2 diabetes.

  15. Estrogen receptor prevents p53-dependent apoptosis in breast cancer

    OpenAIRE

    Bailey, Shannon T.; Shin, Hyunjin; Westerling, Thomas; Liu, Xiaole Shirley; Brown, Myles

    2012-01-01

    More than two-thirds of breast cancers express the estrogen receptor (ER) and depend on estrogen for growth and survival. Therapies targeting ER function, including aromatase inhibitors that block the production of estrogens and ER antagonists that alter ER transcriptional activity, play a central role in the treatment of ER+ breast cancers of all stages. In contrast to ER− breast cancers, which frequently harbor mutations in the p53 tumor suppressor, ER+ breast cancers are predominantly wild...

  16. Chromium(VI) transport and fate in unsaturated zone and aquifer: 3D Sandbox results.

    Science.gov (United States)

    Zhao, Xingmin; Sobecky, Patricia A; Zhao, Lanpo; Crawford, Patrice; Li, Mingtang

    2016-04-01

    The simulation of Cr(VI) behavior in an unsaturated zone and aquifer, using a 3D experimental set-up were performed to illustrate the distribution, transport and transformation of Cr(VI), and further to reveal the potential harm of Cr(VI) after entering the groundwater. The result indicated that chromium(VI) was transported in the vertical direction, meanwhile, was transported in the horizontal direction under the influence of groundwater flow. The direction and distance away from the pollution source zone had great effect on the chromium(VI) concentration. At the sampling sites near the pollution source zone, there was a sudden increase of chromium(VI) concentration. The concentration of chromium(III) concentration in some random effluent samples was not detected. Chromium had not only transported but also had fraction and specie transformation in the unsaturated zone and aquifer. The relative concentration of residue fraction chromium was decreased with time. The content of Fe-Mn oxide fraction chromium was increased with time. The relative content of exchangeable and carbonate-bound fraction chromium was lower and the content variations were not obvious. Chromium(VI) (91-98%) was first reduced to chromium(III) rapidly. The oxidation reaction occurred later and the relative content of chromium(VI) was increased again. The presence of manganese oxides under favorable soil conditions can promote the reoxidation of Cr(III) to Cr(VI).

  17. Structure and morphology studies of chromium film at elevated temperature in hypersonic environment

    Indian Academy of Sciences (India)

    G M Hegde; V Kulkarni; M Nagaboopathy; K P J Reddy

    2012-06-01

    This paper presents the after shock heated structural and morphological studies of chromium film coated on hypersonic test model as a passive drag reduction element. The structural changes and the composition of phases of chromium due to shock heating (2850 K) are characterized using X-ray diffraction studies. Surface morphology changes of chromium coating have been studied using scanning electron microscopy (SEM) before and after shock heating. Significant amount of chromium ablation and sublimation from the model surface is noticed from SEM micrographs. Traces of randomly oriented chromium oxides formed along the coated surface confirm surface reaction of chromium with oxygen present behind the shock. Large traces of amorphous chromium oxide phases are also observed.

  18. Determination of Chromium in Beef Heifers Nellore Supplemented with Chelate Chrome

    Directory of Open Access Journals (Sweden)

    P.S.A Moreira

    2013-11-01

    Full Text Available The objective of this work was to determine the amount of total chromium in beef heifers supplemented with chelated chromium in the rearing and finishing. We used 80 Nelore heifers at 12 months of age with mineral supplementation associated or not to chelate chromium, with average live weight of 220 kg. Were selected 36 heifer seach experimental group for analysis of meat samples. For the determination of chromium residue in the muscle tissue of the sample was1.5 g digested in a mixture of 5 ml 65% nitric acid and 1 ml of 30% hydrogen peroxide at 120° C for 12 hours block microdigestor. The total content of chromium was determined by spectrophotometry of atomic absorption flame. The experimental design was completely randomized and the results were analyzed by analysis of variance (ANOVA at 5% significance. It is concluded that the inclusion of chromium in the chelate heifers mineral supplementation increased the chromium content in the meat

  19. Contribution of photoelectron spectrometry and infrared spectrometry to the study of various oxidised forms of chromium

    International Nuclear Information System (INIS)

    Securate knowledge of internal surface of primary coolant circuits of PWR is required for an estimation of dissolution of used materials and for estimation of decontamination efficiency. The binding energies of various electron levels of chromium were determined by photoelectron spectrometry (ESCA), both for the metal and for certain compounds. Because of the intensities of the signals obtained the 2 p 3/2 level alone can be used for analytical purposes. Owing to a possible interference between this level due to hexavalent chromium and a satellite peak caused by trivalent chromium the method is not able to show up small amounts of chromium VI in chromium III. Simultaneous detection of the hexavalent and trivalent forms was achieved by infrared spectrometry. The problem of revealing traces of chromium VI in surface layers of trivalent chromium oxide has thus been solved

  20. The p53-dependent radioadaptive response

    Science.gov (United States)

    Ohnishi, Takeo

    We already reported that conditioning exposures at low doses, or at low dose-rates, lowered radiation-induced p53-dependent apoptosis in cultured cells in vitro and in the spleens of mice in vivo. In this study, the aim was to characterize the p53-dependent radioadaptive response at the molecular level. We used wild-type (wt) p53 and mutated (m) p53 containing cells derived from the human lung cancer H1299 cell line, which is p53-null. Cellular radiation sensitivities were determined with a colony-forming assay. The accumulation of p53, Hdm2, and iNOS was analyzed with Western blotting. The quantification of chromosomal aberrations was estimated by scoring dicentrics per cell. In wtp53 cells, it was demonstrated that the lack of p53 accumulation was coupled with the activation of Hdm2 after low dose irradiation (0.02 Gy). Although NO radicals were only minimally induced in wtp53 cells irradiated with a challenging irradiation (6 Gy) alone, NO radicals were seen to increase about 2-4 fold after challenging irradiation following a priming irradiation (0.02 Gy). Under similar irradiation conditions with a priming and challenging irradiation in wtp53 cells, induction of radioresistance and a depression of chromosomal aberrations were observed only in the absence of Pifithrin-α (a p53 inhibitor), RITA or Nutlin-3 (p53-Hdm2 interaction inhibitors), aminoguanidine (an iNOS inhibitor) and c-PTIO (an NO radical scavenger). On the other hand, in p53 dysfunctional cells, a radioadaptive response was not observed in the presence or absence of those inhibitors. Moreover, radioresistance developed when wtp53 cells were treated with ISDN (an NO generating agent) alone. These findings suggest that NO radicals are an initiator of the radioadaptive response acting through the activation of Hdm2 and the depression of p53 accumulations.

  1. Bioaccumulation and depuration of chromium in the selected organs and whole body tissues of freshwater fish Cirrhinus mrigala individually and in binary solutions with nickel

    Institute of Scientific and Technical Information of China (English)

    PL. RM. Palaniappan; S. Karthikeyan

    2009-01-01

    Contamination of aquatic ecosystems with heavy metals has been receiving increased worldwide attention due to their harmful effects on human health and other organisms in the environment.Most of the studies dealing with toxic effects of metals deal with single metal species, while the aquatic organisms are typically exposed to mixtures of metals.Hence, in order to provide data supporting the usefulness of freshwater fish as indicators of heavy metal pollution, it has been proposed in the present study to investigate the bioaccumulation and depuration of chromium in the selected organs of freshwater fingerlings Cirrhinus mrigala, individually and in binary solutions with nickel.The results show that the kidney is a target organ for chromium accumulation, which implies that it is also the "critical" organ for toxic symptoms.The results further show that accumulation of nickel in all the tissues of C.mrigala is higher than that of chromium.In addition, the metal accumulations of the binary mixtures of chromium and nickel are substantially higher than those of the individual metals, indicating synergistic interactions between the two metals.Theoretically the simplest explanation for an additive joint action of toxicants in a mixture is that they act in a qualitatively similar way.The observed data suggest that C.mrigala could be suitable monitoring organisms to study the bioavailability of water-bound metals in freshwater habitats.

  2. Laboratory scale studies on removal of chromium from industrial wastes

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Chromium being one of the major toxic pollutants is discharged from electroplating and chrome tanning processes and is also found in the effluents of dyes, paint pigments, manufacturing units etc. Chromium exists in aqueous systems in both trivalent (Cr 3+) and hexavalent (Cr 6+) forms. The hexavalent form is carcinogenic and toxic to aquatic life, whereas Cr3+ is however comparatively less toxic. This study was undertaken to investigate the total chromium removal from industrial effluents by chemical means in order to achieve the Pakistan NEQS level of 1 mg/L by the methods of reduction and precipitation. The study was conducted in four phases.In phase I, the optimum pH and cost effective reducing agent among the four popular commercial chemicals was selected. As a result, pH of 2 was found to be most suitable and sodium meta bisulfate was found to be the most cost effective reducing agent respectively. Phase II showed that lower dose of sodium meta bisulfate was sufficient to obtain 100 % efficiency in reducing Cr6+ to Cr3+, and it was noted that reaction time had no significance in the whole process. A design curve for reduction process was established which can act as a tool for treatment of industrial effluents.Phase III studies indicated the best pH was 8.5 for precipitation of Cr 3+ to chromium hydroxide by using lime. An efficiency of 100 % was achievable and a settling time of 30 minutes produced clear effluent. Finally in Phase IV actual waste samples from chrome tanning and electroplating industries, when precipitated at pH of 12 gave 100 % efficiency at a settling time of 30 minutes and confirmed that chemical means of reduction and precipitation is a feasible and viable solution for treating chromium wastes from industries.

  3. Arsenic and chromium topsoil levels and cancer mortality in Spain.

    Science.gov (United States)

    Núñez, Olivier; Fernández-Navarro, Pablo; Martín-Méndez, Iván; Bel-Lan, Alejandro; Locutura, Juan F; López-Abente, Gonzalo

    2016-09-01

    Spatio-temporal cancer mortality studies in Spain have revealed patterns for some tumours which display a distribution that is similar across the sexes and persists over time. Such characteristics would be common to tumours that shared risk factors, including the chemical soil composition. The objective of the present study is to assess the association between levels of chromium and arsenic in soil and the cancer mortality. This is an ecological cancer mortality study at municipal level, covering 861,440 cancer deaths in 7917 Spanish mainland towns from 1999 to 2008. Chromium and arsenic topsoil levels (partial extraction) were determined by ICP-MS at 13,317 sampling points. To estimate the effect of these concentrations on mortality, we fitted Besag, York and Mollié models, which included, as explanatory variables, each town's chromium and arsenic soil levels, estimated by kriging. In addition, we also fitted geostatistical-spatial models including sample locations and town centroids (non-aligned data), using the integrated nested Laplace approximation (INLA) and stochastic partial differential equations (SPDE). All results were adjusted for socio-demographic variables and proximity to industrial emissions. The results showed a statistical association in men and women alike, between arsenic soil levels and mortality due to cancers of the stomach, pancreas, lung and brain and non-Hodgkin's lymphomas (NHL). Among men, an association was observed with cancers of the prostate, buccal cavity and pharynx, oesophagus, colorectal and kidney. Chromium topsoil levels were associated with mortality among women alone, in cancers of the upper gastrointestinal tract, breast and NHL. Our results suggest that chronic exposure arising from low levels of arsenic and chromium in topsoil could be a potential risk factor for developing cancer.

  4. Sorption of chromium in soils of the Cerrado Goias, Brazil

    Directory of Open Access Journals (Sweden)

    Welershon José de Castro

    2010-08-01

    Full Text Available Land application of tannery sludge, which usually contain high levels of chromium, and considerable amounts of organic matter, macronutrients and micronutrients may contribute to the improvement of soil fertility and plant nutrition, and constitutes a form of disposal residue in the environment. The objective of this work was to determine the sorption isotherms of metal chromium (Cr+3 in a Ultisol, Oxisol Typic Acrustox, Quartzipsamment and Kandic Oxisol, identify soil classes that are prone to chromium mobility, and characterize the potential of agricultural soils of Goiás that are subject to groundwater contamination by the potentially toxic metal. For the establishment of sorption isotherms, solutions were prepared at 1:10 in volume. Air dried samples of 5.0 cm3 of each class of soil were placed in triplicates in beakers of 250.0 cm3. A solution containing 50.0 cm3 of the potentially toxic metal was added to solution. The solutions were prepared in CaCl2.(2H2O (0.01 mol.L-1 as electrolyte support and employing the basic chromium sulphate as a source of metal. Adjustments were made to the polynomial regression between the concentrations of potentially toxic levels of metal contaminants in the solution depending on the concentration of metal in the filtered solution after equilibrium. The Quartzipsamment showed lower retention compared to other classes of soils. Therefore it is more vulnerable to groundwater contamination if industrial wastes containing trivalent chromium are used as fertilizer.

  5. Aggregation tendencies in the p53 family are modulated by backbone hydrogen bonds.

    Science.gov (United States)

    Cino, Elio A; Soares, Iaci N; Pedrote, Murilo M; de Oliveira, Guilherme A P; Silva, Jerson L

    2016-01-01

    The p53 family of proteins is comprised of p53, p63 and p73. Because the p53 DNA binding domain (DBD) is naturally unstable and possesses an amyloidogenic sequence, it is prone to form amyloid fibrils, causing loss of functions. To develop p53 therapies, it is necessary to understand the molecular basis of p53 instability and aggregation. Light scattering, thioflavin T (ThT) and high hydrostatic pressure (HHP) assays showed that p53 DBD aggregates faster and to a greater extent than p63 and p73 DBDs, and was more susceptible to denaturation. The aggregation tendencies of p53, p63, and p73 DBDs were strongly correlated with their thermal stabilities. Molecular Dynamics (MD) simulations indicated specific regions of structural heterogeneity unique to p53, which may be promoted by elevated incidence of exposed backbone hydrogen bonds (BHBs). The results indicate regions of structural vulnerability in the p53 DBD, suggesting new targetable sites for modulating p53 stability and aggregation, a potential approach to cancer therapy. PMID:27600721

  6. Tumor suppressor protein C53 antagonizes checkpoint kinases to promote cyclin-dependent kinase 1 activation

    Institute of Scientific and Technical Information of China (English)

    Hai Jiang; Jianchun Wu; Chen He; Wending Yang; Honglin Li

    2009-01-01

    Cyclin-dependent kinase 1 (Cdk1)/cyclin B1 complex is the driving force for mitotic entry, and its activation is tightly regulated by the G2/M checkpoint. We originally reported that a novel protein C53 (also known as Cdk5rap3 and LZAP) potentiates DNA damage-induced cell death by modulating the G2/M checkpoint. More recently, Wang et al. (2007) found that C53/LZAP may function as a tumor suppressor by way of inhibiting NF-kB signaling. We report here the identification of C53 protein as a novel regulator of Cdk1 activation. We found that knockdown of C53 protein causes delayed Cdkl activation and mitotic entry. During DNA damage response, activation of checkpoint kinase 1 and 2 (Chk1 and Chk2) is partially inhibited by C53 overexpression. Intriguingly, we found that C53 interacts with Chkl and antagonizes its function. Moreover, a portion of C53 protein is localized at the centrosome, and centrosome-targeting C53 potently promotes local Cdk1 activation. Taken together, our results strongly suggest that C53 is a novel negative regulator of checkpoint response. By counteracting Chk1, C53 promotes Cdk1 activation and mitotic entry in both unperturbed cell-cycle progression and DNA damage response.

  7. Aggregation tendencies in the p53 family are modulated by backbone hydrogen bonds

    Science.gov (United States)

    Cino, Elio A.; Soares, Iaci N.; Pedrote, Murilo M.; de Oliveira, Guilherme A. P.; Silva, Jerson L.

    2016-01-01

    The p53 family of proteins is comprised of p53, p63 and p73. Because the p53 DNA binding domain (DBD) is naturally unstable and possesses an amyloidogenic sequence, it is prone to form amyloid fibrils, causing loss of functions. To develop p53 therapies, it is necessary to understand the molecular basis of p53 instability and aggregation. Light scattering, thioflavin T (ThT) and high hydrostatic pressure (HHP) assays showed that p53 DBD aggregates faster and to a greater extent than p63 and p73 DBDs, and was more susceptible to denaturation. The aggregation tendencies of p53, p63, and p73 DBDs were strongly correlated with their thermal stabilities. Molecular Dynamics (MD) simulations indicated specific regions of structural heterogeneity unique to p53, which may be promoted by elevated incidence of exposed backbone hydrogen bonds (BHBs). The results indicate regions of structural vulnerability in the p53 DBD, suggesting new targetable sites for modulating p53 stability and aggregation, a potential approach to cancer therapy. PMID:27600721

  8. Aggregation tendencies in the p53 family are modulated by backbone hydrogen bonds

    Science.gov (United States)

    Cino, Elio A.; Soares, Iaci N.; Pedrote, Murilo M.; de Oliveira, Guilherme A. P.; Silva, Jerson L.

    2016-09-01

    The p53 family of proteins is comprised of p53, p63 and p73. Because the p53 DNA binding domain (DBD) is naturally unstable and possesses an amyloidogenic sequence, it is prone to form amyloid fibrils, causing loss of functions. To develop p53 therapies, it is necessary to understand the molecular basis of p53 instability and aggregation. Light scattering, thioflavin T (ThT) and high hydrostatic pressure (HHP) assays showed that p53 DBD aggregates faster and to a greater extent than p63 and p73 DBDs, and was more susceptible to denaturation. The aggregation tendencies of p53, p63, and p73 DBDs were strongly correlated with their thermal stabilities. Molecular Dynamics (MD) simulations indicated specific regions of structural heterogeneity unique to p53, which may be promoted by elevated incidence of exposed backbone hydrogen bonds (BHBs). The results indicate regions of structural vulnerability in the p53 DBD, suggesting new targetable sites for modulating p53 stability and aggregation, a potential approach to cancer therapy.

  9. Interactions of the p53 protein family in cellular stress response in gastrointestinal tumors.

    Science.gov (United States)

    Vilgelm, Anna E; Washington, Mary K; Wei, Jinxiong; Chen, Heidi; Prassolov, Vladimir S; Zaika, Alexander I

    2010-03-01

    p53, p63, and p73 are members of the p53 protein family involved in regulation of cell cycle, apoptosis, differentiation, and other critical cellular processes. Here, we investigated the contribution of the entire p53 family in chemotherapeutic drug response in gastrointestinal tumors. Real-time PCR and immunohistochemistry revealed complexity and variability of expression profiles of the p53 protein family. Using colon and esophageal cancer cells, we found that the integral transcription activity of the entire p53 family, as measured by the reporter analysis, associated with response to drug treatment in studied cells. We also found that p53 and p73, as well as p63 and p73, bind simultaneously to the promoters of p53 target genes. Taken together, our results support the view that the p53 protein family functions as an interacting network of proteins and show that cellular responses to chemotherapeutic drug treatment are determined by the total activity of the entire p53 family rather than p53 alone.

  10. Allele Specific p53 Mutant Reactivation

    OpenAIRE

    Yu, Xin; Vazquez, Alexei; Levine, Arnold J.; Carpizo, Darren R.

    2012-01-01

    Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Using the NCI anticancer drug screen data, we identified two compounds from the thiosemicarbazone family that manifest increased growth inhibitory activity in mutant p53 cells, particularly for the p53R175 mutant. Mechanistic studies reveal that NSC319726 restores WT structure and function to the p53R175 mutant. This compound kills p53R172H knock-in mice with extensive apoptosis and inhibits xenograft tu...

  11. Raman spectroscopy of supported chromium oxide catalysts : determination of chromium-oxygen bond distances and bond orders

    NARCIS (Netherlands)

    Weckhuysen, B.M.; Wachs, I.E.

    1996-01-01

    An empirical correlation is described for relating Raman stretching frequencies of chromium—oxygen (Cr—O) bonds to their bond lengths in chromium oxide reference compounds. An exponential fit of crystallographically determined Cr—O bond lengths to Cr—O Raman symmetric stretching frequencies (800–130

  12. Reduction of hexavalent chromium by ferrous iron: A process of chromium isotope fractionation and its relevance to natural environments

    DEFF Research Database (Denmark)

    Døssing, Lasse Nørbye; Dideriksen, Knud; Stipp, Susan Louise Svane;

    2011-01-01

    Stable chromium (Cr) isotopes can be used as a tracer for changing redox conditions in modern marine systems and in the geological record. We have investigated isotope fractionation during reduction of Cr(VI)aq by Fe(II)aq. Reduction of Cr(VI)aq by Fe(II)aq in batch experiments leads to significant...

  13. Chromium- and copper-induced inhibition of photosynthesis in Euglena gracilis analysed on the single-cell level by fluorescence kinetic microscopy

    OpenAIRE

    Rocchetta, Iara; Küpper, Hendrik

    2009-01-01

    Here. we investigated effects of copper (Cu) and chromium (Cr) toxicity on two contrasting strains of Euglena gracilis, with and without chloroplasts, grown in culture media promoting either phototrophic or heterotrophic growth. This led to insights into Cr/Cu toxicity mechanisms and into the regulation of phototrophic vs heterotrophic metabolism.Our data strongly suggest that in Cu2+ and Cr6+ stressed Euglena photosynthesis is the primary target of damage. In the applied light conditions, th...

  14. Interplay among p53, MDM2, and MDMX and Progress in Related Studies%p53与MDM2及MDMX 的相互作用和研究进展

    Institute of Scientific and Technical Information of China (English)

    李小龙

    2012-01-01

    p53是重要的抑癌基因,在细胞周期阻滞、DNA损伤修复及细胞凋亡等生物过程中发挥重要作用,并已成为潜在的肿瘤治疗靶点.MDM2(Mdm2 p53 binding protein homolog)及MDMX(Mdm4 p53 binding protein homolog)是p53的主要抑制因子,两者相互协同并通过不同的信号途径抑制p53的活性.MDM2是p53的E3连接酶,介导p53的泛素化从而降低p53的稳定性.MDMX则主要通过与p53的转录活性区结合,抑制p53对其下游基因的转录活性,但并不介导p53的降解.MDM2与MDMX通过不同机制协同对p53产生抑制作用,其具体分子过程及作用机制繁多且复杂.本文就p53、MDM2及MDMX的相互作用及各蛋白的功能进行综述.%P53 is one of the most important tumor suppressors. The resukts from functional analysis revealed that p53 is a potent stress responder that regulates cell-cycle arrest, DNA repair, cell senescence, and apoptosis. P53 is also recognized as a potential therapy target. MDM2 and MDMX are two major p53 suppressors, which can both inhibit p53 activity via different mechanisms. MDM2 is an E3 ligase of p53, which can promote p53 ubiquitination and can regulate p53 degradation and stabilization. MDMX does not have E3 ligase activity, but can directly bind to the N terminus of p53 and can inhibit p53 transactivation. Studies have shown that MDM2 and MDMX could work together to regulate p53 activity in a more complicated mechanism. The present work reviews the interplay among p53, MDM2, and MDMX.

  15. Updates on p53: modulation of p53 degradation as a therapeutic approach

    OpenAIRE

    Dey, A; Verma, C S; LANE, D. P.

    2008-01-01

    The p53 pathway is aberrant in most human tumours with over 50% expressing mutant p53 proteins. The pathway is critically controlled by protein degradation. Here, we discuss the latest developments in the search for small molecules that can modulate p53 pathway protein stability and restore p53 activity for cancer therapy.

  16. Cellular functions of p53 and p53 gene family members p63 and p73

    Directory of Open Access Journals (Sweden)

    Nadir Koçak

    2011-12-01

    Full Text Available p53 is a transcription factor that regulates multiple cellular processes that are also important in cellular fates such as cell cycle arrest or programmed cell death. Induction of growth arrest or cell death by p53 prevents the replication of damaged DNA and proliferation of genetically abnormal cells. Therefore, inactivation of p53 by mutation or deletion is also important in ensuring the cellular homeostasis. However, studies showed that p53 deficient mice and cells such as Saos-2 cells are maintaining their life. This situation suggests that p53-related proteins might compensate the functions of p53 in p53 deficient organisms. The identification of two p53-related proteins, p63 and p73 revealed the transcription of p53 responsive genes in p53 deficient organisms. Both p63 and p73 proteins have high homology with the p53 protein and share some of the functions of p53. In contrast to p53, p63 and p73 rarely mutated in human cancers. Here we studied to summarize the current information about the p53 and other p53-related proteins, p63 and p73 that are included into the p53 gene family.

  17. p53 transactivation and the impact of mutations, cofactors and small molecules using a simplified yeast-based screening system.

    Directory of Open Access Journals (Sweden)

    Virginia Andreotti

    Full Text Available BACKGROUND: The p53 tumor suppressor, which is altered in most cancers, is a sequence-specific transcription factor that is able to modulate the expression of many target genes and influence a variety of cellular pathways. Inactivation of the p53 pathway in cancer frequently occurs through the expression of mutant p53 protein. In tumors that retain wild type p53, the pathway can be altered by upstream modulators, particularly the p53 negative regulators MDM2 and MDM4. METHODOLOGY/PRINCIPAL FINDINGS: Given the many factors that might influence p53 function, including expression levels, mutations, cofactor proteins and small molecules, we expanded our previously described yeast-based system to provide the opportunity for efficient investigation of their individual and combined impacts in a miniaturized format. The system integrates i variable expression of p53 proteins under the finely tunable GAL1,10 promoter, ii single copy, chromosomally located p53-responsive and control luminescence reporters, iii enhanced chemical uptake using modified ABC-transporters, iv small-volume formats for treatment and dual-luciferase assays, and v opportunities to co-express p53 with other cofactor proteins. This robust system can distinguish different levels of expression of WT and mutant p53 as well as interactions with MDM2 or 53BP1. CONCLUSIONS/SIGNIFICANCE: We found that the small molecules Nutlin and RITA could both relieve the MDM2-dependent inhibition of WT p53 transactivation function, while only RITA could impact p53/53BP1 functional interactions. PRIMA-1 was ineffective in modifying the transactivation capacity of WT p53 and missense p53 mutations. This dual-luciferase assay can, therefore, provide a high-throughput assessment tool for investigating a matrix of factors that can influence the p53 network, including the effectiveness of newly developed small molecules, on WT and tumor-associated p53 mutants as well as interacting proteins.

  18. The Histone Lysine Demethylase JMJD3/KDM6B Is Recruited to p53 Bound Promoters and Enhancer Elements in a p53 Dependent Manner

    DEFF Research Database (Denmark)

    Williams, Kristine; Christensen, Jesper; Rappsilber, Juri;

    2014-01-01

    find that the interaction is dependent on the p53 tetramerization domain. Following DNA damage, JMJD3 is transcriptionally upregulated and by performing genome-wide mapping of JMJD3, we demonstrate that it binds genes involved in basic cellular processes, as well as genes regulating cell cycle......, response to stress and apoptosis. Moreover, we find that JMJD3 binding sites show significant overlap with p53 bound promoters and enhancer elements. The binding of JMJD3 to p53 target sites is increased in response to DNA damage, and we demonstrate that the recruitment of JMJD3 to these sites is dependent...

  19. Disruption of focal adhesion kinase and p53 interaction with small molecule compound R2 reactivated p53 and blocked tumor growth

    OpenAIRE

    Golubovskaya, Vita M.; Ho, Baotran; Zheng, Min; Magis, Andrew; Ostrov, David; Morrison, Carl; Cance, William G.

    2013-01-01

    Background Focal Adhesion Kinase (FAK) is a 125 kDa non-receptor kinase that plays a major role in cancer cell survival and metastasis. Methods We performed computer modeling of the p53 peptide containing the site of interaction with FAK, predicted the peptide structure and docked it into the three-dimensional structure of the N-terminal domain of FAK involved in the complex with p53. We screened small molecule compounds that targeted the site of the FAK-p53 interaction and identified compoun...

  20. Activated carbon adsorption for chromium treatment and recovery; Adsorbimento di cromo su carboni attivi a scopo di recupero e decontaminazione

    Energy Technology Data Exchange (ETDEWEB)

    Baroncelli, F.; Castelli, S.; De Francesco, M. [ENEA, Casaccia (Italy). Area Energia e Innovazione

    1994-05-01

    The capability of actived carbon systems to adsorb chromium from wastewater of galvanic industry is valued. Batch tests and column tests are carried out with good results. An activated carbon with acidic surface oxides can adsorb both chromate and chromium (III); chromate is reduced in situ and then adsorbed as chromium (III). Chromium can be desorbed from carbon by an acid or basic treatment obtaining respectively chromium (III) or chromate solutions. Carbon can be regenerated many times without evident signs of deterioration.

  1. The effect of dietary supplementation with different forms and levels of organic chromium on broilers meat quality

    OpenAIRE

    Keleman Svetlana P.; Kevrešan Slavko E.; Supić Boriša; Perić Lidija; Strugar Vladimir

    2006-01-01

    This paper deals with the effect of supplementation with the three different preparations of organic chromium complexes: the ethylenediaminetetraacetic acid complex with chromium; chromium (III)­lysine and chromium picolinate, on broilers meat quality. In every preparation supplementing broilers diet chromium was present at the three different levels: 0.2; 0.4 and 0.6 mg/kg. The meat quality was monitored with respect to the following parameters: the contents of fat, protein, minerals and wat...

  2. Expression screening using a Medaka cDNA library identifies evolutionarily conserved regulators of the p53/Mdm2 pathway

    OpenAIRE

    P. Zhang; Kratz, A.S.; M. Salama; Elabd, S.; Heinrich, T; Wittbrodt, J.; Blattner, C.; G Davidson

    2015-01-01

    Background The p53 tumor suppressor protein is mainly regulated by alterations in the half-life of the protein, resulting in significant differences in p53 protein levels in cells. The major regulator of this process is Mdm2, which ubiquitinates p53 and targets it for proteasomal degradation. This process can be enhanced or reduced by proteins that associate with p53 or Mdm2 and several proteins have been identified with such an activity. Furthermore, additional ubiquitin ligases for p53 have...

  3. Tumor suppressor p53: analysis of wild-type and mutant p53 complexes.

    OpenAIRE

    Milner, J; Medcalf, E A; Cook, A. C.

    1991-01-01

    It has been suggested that the dominant effect of mutant p53 on tumor progression may reflect the mutant protein binding to wild-type p53, with inactivation of suppressor function. To date, evidence for wild-type/mutant p53 complexes involves p53 from different species. To investigate wild-type/mutant p53 complexes in relation to natural tumor progression, we sought to identify intraspecific complexes, using murine p53. The mutant phenotype p53-246(0) was used because this phenotype is immuno...

  4. Effect of recasting on the thickness of metal-ceramic interface of nickel-chromium and cobalt-chromium alloys

    Directory of Open Access Journals (Sweden)

    Mirković Nemanja

    2008-01-01

    Full Text Available Introduction/Aim. This research was done to establish recasting effects of nickel-chromium and cobalt-chromium alloys on the thickness of their metal-ceramic interface in making fixed partial dentures. Metal-ceramic interface determines their functional integrity and prevents damages on ceramics during mastication. Investigation of metal-ceramic samples is supposed to show if base metal alloys for metalceramics are successfully recycled without any risk of reduction of metal-ceramic interface thickness. Methods. The research was performed as an experimental study. Per six metal-ceramic samples of nickel-chromium alloy (Wiron99 and cobalt-chromium alloy (Wirobond C were made each. Alloy residues were recycled through twelve casting generations with the addition of 50% of new alloy on the occasion of every recasting. Analysis Energy Dispersive X-ray (EDX (Oxford Instruments and Scanning Electon Microscop (SEM analysis (JEOL were used to determine thickness of metal-ceramic interface together with PC Software for quantification of visual information's (KVI POPOVAC. Results. Results of this research introduced significant differences between thickness of metal-ceramic interface in every examined recycle generation. Recasting had negative effect on thickness of metal-ceramic interface of the examined alloys. This research showed almost linear reduction of elastic modulus up to the 12th generation of recycling. Conclusion. Recasting of nickel-chromium and cobaltchromium alloys is not recommended because of reduced thickness of metal-ceramic interface of these alloys. Instead of recycling, the alloy residues should be returned to the manufacturers.

  5. Bioadsorption and bioaccumulation of chromium trivalent in Cr(III)-tolerant microalgae: a mechanisms for chromium resistance.

    Science.gov (United States)

    Pereira, M; Bartolomé, M C; Sánchez-Fortún, S

    2013-10-01

    Anthropogenic activity constantly releases heavy metals into the environment. The heavy metal chromium has a wide industrial use and exists in two stable oxidation states: trivalent and hexavalent. While hexavalent chromium uptake in plant cells has been reported that an active process by carrying essential anions, the cation Cr(III) appears to be taken up inactively. Dictyosphaerium chlorelloides (Dc1M), an unicellular green alga is a well-studied cell biological model organism. The present study was carried out to investigate the toxic effect of chromium exposures on wild-type Cr(III)-sensitive (Dc1M(wt)) and Cr(III)-tolerant (Dc1M(Cr(III)R30)) strains of these green algae, and to determine the potential mechanism of chromium resistance. Using cell growth as endpoint to determine Cr(III)-sensitivity, the IC₅₀(₇₂) values obtained show significant differences of sensitivity between wild type and Cr(III)-tolerant cells. Scanning electron microscopy (SEM) showed significant morphological differences between both strains, such as decrease in cell size or reducing the coefficient of form; and transmission electron microscopy (TEM) revealed ultrastructural changes such as increased vacuolization and cell wall thickening in the Cr(III)-tolerant strain with respect to the wild-type strain. Energy dispersive X-ray analysis (SEM/XEDS) revealed that Cr(III)-tolerant D. chlorelloides cells are able to accumulate considerable amounts of chromium distributed in cell wall (bioadsorption) as well as in cytoplasm, vacuoles, and chloroplast (bio-accumulation). Morphological changes of Cr(III)-tolerant D. chlorelloides cells and the presence of these electron-dense bodies in their cell structures can be understood as a Cr(III) detoxification mechanism. PMID:23810518

  6. Hot Corrosion Behavior of High-Chromium, High-Carbon Cast Irons in NaCl-KCl Molten Salts

    Directory of Open Access Journals (Sweden)

    S. Vuelvas-Rayo

    2012-01-01

    Full Text Available A study on the corrosion behavior of a series of experimental high-chromium (18.53–30.48 wt.%, high-carbon (3.82–5.17% cast irons in NaCl-KCl (1 : 1 M at 670°C has been evaluated by using weight loss technique and compared with a 304-type stainless steel. It was found that all castings had a higher corrosion rate than conventional 304SS and that the addition of Cr increased the degradation rate of the cast irons. Additionally, corrosion rate increased by increasing the C contents up to 4.29%, but it decreased with a further increase in its contents. Results are discussed in terms of consumption of the Cr2O3 layer by the melt.

  7. Microstructure and surface properties of chromium-doped diamond-like carbon thin films fabricated by high power pulsed magnetron sputtering

    International Nuclear Information System (INIS)

    High power pulsed magnetron sputtering (HPPMS) has attracted much interest due to the large plasma density and high ionization rate of sputtered materials. It is expected to produce a highly ionized C flux from a graphite target but unfortunately, the ionization rate of carbon is still very small and the discharge on a solid carbon target is unstable as well. In this work, a stable discharged chromium target is used in the preparation of chromium-doped diamond-like carbon (Cr-DLC) films in HPPMS in reactive C2H2 gas, but the unstable graphite. The chromium concentration in the Cr-DLC films is limited by surface poisoning due to reactive gas. Less than 2% of Cr is incorporated into the DLC films at C2H2 flow rate of 5 sccm or higher. However, as a result of the high ionization rate of the reactive gas in HPPMS, intense ion bombardment of the substrate is realized. The films show a smooth surface and a dense structure with a large sp3 concentration. As the C2H2 flow increase, the sp3 fraction increase and the sp3 to sp2 ratio increase to 0.75 at a C2H2 flow rate of 10 sccm. Compared to the substrate, the Cr-DLC films have lower friction and exhibit excellent corrosion resistance.

  8. The heme–p53 interaction: Linking iron metabolism to p53 signaling and tumorigenesis

    OpenAIRE

    Shen, Jia; Sheng, Xiangpeng; Chang, ZeNan; Wu, Qian; Xie, Dong; Wang, Fudi; HU, Ronggui

    2014-01-01

    Recently, we reported that heme binds to tumor suppressor p53 protein (TP53, best known as p53) and promotes its nuclear export and cytosolic degradation, whereas iron chelation stabilizes p53 protein and suppresses tumors in a p53-dependent manner. This not only provides mechanistic insights into tumorigenesis associated with iron excess, but also helps guide the administration of chemotherapy based on iron deprivation in the clinic.

  9. Chromium(VI) but not chromium(III) species decrease mitoxantrone affinity to DNA.

    Science.gov (United States)

    Nowicka, Anna M; Stojek, Zbigniew; Hepel, Maria

    2013-01-31

    Binding of mitoxantrone (MXT) to double-stranded DNA has been investigated as a model drug-DNA binding system to evaluate the effects of various forms of chromium on the binding properties. We have found that Cr(III), which binds strongly to DNA, does not affect the MXT affinity to DNA. In contrast, Cr(VI), in the form of chromate ions CrO(4)(2-), decreases the MXT affinity to DNA despite electrostatic repulsions with phosphate-deoxyribose chains of DNA. The MXT-DNA binding constant was found to decrease from (1.96 ± 0.005) × 10(5) to (0.77 ± 0.018) × 10(5) M(-1) for Cr(VI) concentration changing from 0 to 30 μM. The influence of Cr(VI) on MXT-DNA binding has been attributed to the oxidation of guanine residue, thus interrupting the intercalation of MXT into the DNA double helix at the preferential CpG intercalation site. This supposition is corroborated by the observed increase in the MXT binding site size from 2 bp (base pairs) to 4-6 bp in the presence of Cr(VI). The measurements of the MXT-DNA binding constant and the MXT binding site size on a DNA molecule have been carried out using spectroscopic, voltammetric, and nanogravimetric techniques, providing useful information on the mechanism of the interactions.

  10. Urinary levels of nickel and chromium associated with dental restoration by nickel-chromium based alloys

    Institute of Scientific and Technical Information of China (English)

    Bo Chen; Gang Xia; Xin-Ming Cao; Jue Wang; Bi-Yao Xu; Pu Huang; Yue Chen; Qing-Wu Jiang

    2013-01-01

    This paper aims to investigate if the dental restoration of nickel-chromium based alloy (Ni-Cr) leads to the enhanced excretions of Ni and Cr in urine. Seven hundred and ninety-five patients in a dental hospital had single or multiple Ni-Cr alloy restoration recently and 198 controls were recruited to collect information on dental restoration by questionnaire and clinical examination. Urinary concentrations of Ni and Cr from each subject were measure by graphite furnace atomic absorption spectrometry. Compared to the control group, the urinary level of Ni was significantly higher in the patient group of 〈 1 month of the restoration duration, among which higher Ni excretions were found in those with either a higher number of teeth replaced by dental alloys or a higher index of metal crown not covered with the porcelain. Urinary levels of Cr were significantly higher in the three patient groups of 〈1, 1 to 〈3 and 3 to 〈6 months, especially in those with a higher metal crown exposure index. Linear curve estimations showed better relationships between urinary Ni and Cr in patients within 6-month groups. Our data suggested significant increased excretions of urinary Ni and Cr after dental restoration. Potential short- and long-term effects of Ni-Cr alloy restoration need to be investigated.

  11. A computational investigation of boron-doped chromium and chromium clusters by density functional theory

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The geometries,stabilities and electronic properties of Crn and CrnB(n=2-9) clusters have been systematically investigated by density functional theory.The results suggest that the lowest energy structures for CrnB clusters can be obtained by substituting one Cr atom in Crn+1 clusters with B atom.The geometries of CrnB clusters are similar to that of Crn+1 clusters except for local structural distortion.The second-order difference and fragmentation energy show Cr4,Cr6,Cr8,Cr3B,Cr5B and Cr8B cluster are the most stable among these studied clusters.The impurity B increases the stabilities of chromium cluster.When B is doped on the Crn clusters,cluster geometry does dominate positive role in enhancing their stability.The doped B atom does not change the coupling way of the Cr site in Crn clusters,but breaks the symmetry and the Cr atoms are no longer equivalent.The doped B atom increases the total magnetic moments of Crn in most cases.

  12. A metastable chromium carbide powder obtained by carburization of a metastable chromium oxide

    Energy Technology Data Exchange (ETDEWEB)

    Loubiere, S. [Univ. Paul-Sabatier, Toulouse (France). Lab. de Chimie des Materiaux Inorganique; Laurent, C. [Univ. Paul-Sabatier, Toulouse (France). Lab. de Chimie des Materiaux Inorganique; Bonino, J.P. [Univ. Paul-Sabatier, Toulouse (France). Lab. de Chimie des Materiaux Inorganique; Rousset, A. [Univ. Paul-Sabatier, Toulouse (France). Lab. de Chimie des Materiaux Inorganique

    1996-10-15

    A metastable Cr{sub 3}C{sub 2-x} carbide powder is prepared by carburization of a metastable chromium oxide in H{sub 2}-CH{sub 4} atmosphere under the appropriate conditions (temperature, dwell time and CH{sub 4} content). A very high specific surface area (greater than 210 m{sup 2} g{sup -1}) of the starting oxide is necessary to avoid the formation of the sole stable Cr{sub 3}C{sub 2} phase. The transformation from the stable Cr{sub 3}C{sub 2} to the metastable Cr{sub 3}C{sub 2-x} is observed for the first time. The driving force could be an epitaxial effect between Cr{sub 3}C{sub 2-x} and the surrounding graphite layer. This is consistent with the observation that the formation of graphite layers by CH{sub 4} cracking is easier in the Cr{sub 3}C{sub 2-x}-containing powders. (orig.)

  13. TP53inp1 Gene Is Implicated in Early Radiation Response in Human Fibroblast Cells

    Directory of Open Access Journals (Sweden)

    Nikolett Sándor

    2015-10-01

    Full Text Available Tumor protein 53-induced nuclear protein-1 (TP53inp1 is expressed by activation via p53 and p73. The purpose of our study was to investigate the role of TP53inp1 in response of fibroblasts to ionizing radiation. γ-Ray radiation dose-dependently induces the expression of TP53inp1 in human immortalized fibroblast (F11hT cells. Stable silencing of TP53inp1 was done via lentiviral transfection of shRNA in F11hT cells. After irradiation the clonogenic survival of TP53inp1 knockdown (F11hT-shTP cells was compared to cells transfected with non-targeting (NT shRNA. Radiation-induced senescence was measured by SA-β-Gal staining and autophagy was detected by Acridine Orange dye and microtubule-associated protein-1 light chain 3 (LC3B immunostaining. The expression of TP53inp1, GDF-15, and CDKN1A and alterations in radiation induced mitochondrial DNA deletions were evaluated by qPCR. TP53inp1 was required for radiation (IR induced maximal elevation of CDKN1A and GDF-15 expressions. Mitochondrial DNA deletions were increased and autophagy was deregulated following irradiation in the absence of TP53inp1. Finally, we showed that silencing of TP53inp1 enhances the radiation sensitivity of fibroblast cells. These data suggest functional roles for TP53inp1 in radiation-induced autophagy and survival. Taken together, we suppose that silencing of TP53inp1 leads radiation induced autophagy impairment and induces accumulation of damaged mitochondria in primary human fibroblasts.

  14. P53 dependent and independent apoptosis induced by lidamycin in human colorectal cancer cells.

    Science.gov (United States)

    Chen, Lihui; Jiang, Jianming; Cheng, Chunlei; Yang, Ajing; He, Qiyang; Li, Diandong; Wang, Zhen

    2007-06-01

    Enediyne compound is one class of antibiotics with very potent anti-cancer activity. However, the role of p53 in enediyne antibiotic-induced cell killing remains elusive. Here we reported the involvement of p53 signaling pathway in apoptosis induction by lidamycin (LDM), a member of the enediyne antibiotic family. We found that LDM at low drug concentration of 10 nmol/L induces apoptotic cell death much more effectively in human colorectal cancer cells with wild type p53 than those with mutant or deleted p53. p53 is functionally activated as an early event in response to low dose LDM that precedes the significant apoptosis induction. The primarily activation of mitochondria as well as the activation of p53 transcriptional targets such as Puma, Bad and Bax in HCT116 p53 wild type cells further demonstrates the key role of p53 in mediating the compound-induced apoptosis. This is further supported by the observation that the absence of Bax or Puma decreases apoptosis dramatically while Bcl-2 overexpression confers partially resistance after drug treatment. Activation of p53 signaling pathway leads to activation of caspases and caspases inhibitor VAD-fmk completely blocks low dose LDM induced apoptosis through the inhibition of mitochondria pathway. In contrast, LDM at higher concentration causes rapid apoptosis through more direct DNA damaging mechanism that is independent of activation of p53 and caspases and cannot be blocked by caspase inhibitor. Taken together, LDM induces apoptosis in a p53-dependent manner when given at low doses, but in a p53-independent manner when given at high doses. This dosage-dependent regimen can be applied to cancer clinic based upon the p53 status of cancer patients. PMID:17534142

  15. Clinical utility of recombinant adenoviral human p53 gene therapy: current perspectives

    Directory of Open Access Journals (Sweden)

    Chen GX

    2014-10-01

    Full Text Available Guang-xia Chen,1,* Shu Zhang,2–4,* Xiao-hua He,1 Shi-yu Liu,1 Chao Ma,2–4 Xiao-Ping Zou2–4 1Department of Gastroenterology, First People’s Hospital of Xuzhou, Xuzhou, Jiangsu Province, People’s Republic of China; 2Department of Gastroenterology, Drum Tower Hospital, 3Medical School of Nanjing University, 4Jiangsu Clinical Medical Center of Digestive Disease, Nanjing, People’s Republic of China *These authors have contributed equally to the paperAbstract: Gene therapy has promised to be a highly effective antitumor treatment by introducing a tumor suppressor gene or the abrogation of an oncogene. Among the potential therapeutic transgenes, the tumor suppressor gene p53 serves as an attractive target. Restoration of wild-type p53 function in tumors can be achieved by introduction of an intact complementary deoxyribonucleic acid copy of the p53 gene using a suitable viral vector, in most cases an adenoviral vector (Adp53. Preclinical in vitro and in vivo studies have shown that Adp53 triggers a dramatic tumor regression response in various cancers. These viruses are engineered to lack certain early proteins and are thus replication defective, including Gendicine, SCH-58500, and Advexin. Several types of tumor-specific p53-expressing conditionally replicating adenovirus vectors (known as replication-competent CRAdp53 vectors have been developed, such as ONYX 015, AdDelta24-p53, SG600-p53, OBP-702, and H101. Various clinical trials have been conducted to investigate the safety and efficiency of these adenoviral vectors. In this review we will talk about the biological mechanisms, clinical utility, and therapeutic potentials of the replication-deficient Adp53-based and replication-competent CRAdp53-based gene therapy.Keywords: adenovirus, Adp53, CRAdp53

  16. Genome-scale functional analysis of the human genes modulating p53 activity by regulating MDM2 expression in a p53-independent manner.

    Science.gov (United States)

    Kim, Dong Min; Choi, Seung-Hyun; Yeom, Young Il; Min, Sang-Hyun; Kim, Il-Chul

    2016-09-16

    MDM2, a critical negative regulator of p53, is often overexpressed in leukemia, but few p53 mutations are found, suggesting that p53-independent MDM2 expression occurs due to alterations in MDM2 upstream regulators. In this study, a high MDM2 transcription level was observed (41.17%) regardless of p53 expression in patient with acute myeloid leukemia (AML). Therefore, we performed genome-scale functional screening of the human genes modulating MDM2 expression in a p53-independent manner. We searched co-expression profiles of genes showing a positive or negative pattern with MDM2 expression in a DNA microarray database, selected1089 links, and composed a screening library of 368 genes. Using MDM2 P1 and P2 promoter-reporter systems, we screened clones regulating MDM2 transcriptions in a p53-independent manner by overexpression. Nine clones from the screening library showed enhanced MDM2 promoter activity and MDM2 expression in p53-deficient HCT116 cells. Among them, six clones, including NTRK2, GNA15, SFRS2, EIF5A, ELAVL1, and YWHAB mediated MAPK signaling for expressing MDM2. These results indicate that p53-independent upregulation of MDM2 by increasing selected clones may lead to oncogenesis in AML and that MDM2-modulating genes are novel potential targets for AML treatment. PMID:27524244

  17. The novel fusion proteins, GnRH-p53 and GnRHIII-p53, expression and their anti-tumor effect.

    Directory of Open Access Journals (Sweden)

    Peiyuan Jia

    Full Text Available p53, one of the most well studied tumor suppressor factor, is responsible to a variety of damage owing to the induction of apoptosis and cell cycle arrest in the tumor cells. More than 50% of human tumors contain mutation or deletion of p53. Gonadotrophin-releasing hormone (GnRH, as the ligand of Gonadotrophin-releasing hormone receptor (GnRH-R, was used to deliver p53 into tumor cells. The p53 fusion proteins GnRH-p53 and GnRH iii-p53 were expressed and their targeted anti-tumor effects were determined. GnRH mediates its fusion proteins transformation into cancer cells. The intracellular delivery of p53 fusion proteins exerted the inhibition of the growth of H1299 cells in vitro and the reduction of tumor volume in vivo. Their anti-tumor effect was functioned by the apoptosis and cell cycle arrest induced by p53. Hence, the fusion protein could be a novel protein drug for anti-tumor therapy.

  18. Genome-scale functional analysis of the human genes modulating p53 activity by regulating MDM2 expression in a p53-independent manner.

    Science.gov (United States)

    Kim, Dong Min; Choi, Seung-Hyun; Yeom, Young Il; Min, Sang-Hyun; Kim, Il-Chul

    2016-09-16

    MDM2, a critical negative regulator of p53, is often overexpressed in leukemia, but few p53 mutations are found, suggesting that p53-independent MDM2 expression occurs due to alterations in MDM2 upstream regulators. In this study, a high MDM2 transcription level was observed (41.17%) regardless of p53 expression in patient with acute myeloid leukemia (AML). Therefore, we performed genome-scale functional screening of the human genes modulating MDM2 expression in a p53-independent manner. We searched co-expression profiles of genes showing a positive or negative pattern with MDM2 expression in a DNA microarray database, selected1089 links, and composed a screening library of 368 genes. Using MDM2 P1 and P2 promoter-reporter systems, we screened clones regulating MDM2 transcriptions in a p53-independent manner by overexpression. Nine clones from the screening library showed enhanced MDM2 promoter activity and MDM2 expression in p53-deficient HCT116 cells. Among them, six clones, including NTRK2, GNA15, SFRS2, EIF5A, ELAVL1, and YWHAB mediated MAPK signaling for expressing MDM2. These results indicate that p53-independent upregulation of MDM2 by increasing selected clones may lead to oncogenesis in AML and that MDM2-modulating genes are novel potential targets for AML treatment.

  19. p53 contributes to T cell homeostasis through the induction of pro-apoptotic SAP.

    Science.gov (United States)

    Madapura, Harsha S; Salamon, Daniel; Wiman, Klas G; Lain, Sonia; Klein, George; Klein, Eva; Nagy, Noémi

    2012-12-15

    Lack of functional SAP protein, due to gene deletion or mutation, is the cause of X-linked lymphoproliferative disease (XLP), characterized by functionally impaired T and NK cells and a high risk of lymphoma development. We have demonstrated earlier that SAP has a pro-apoptotic function in T and B cells. Deficiency of this function might contribute to the pathogenesis of XLP. We have also shown that SAP is a target of p53 in B cell lines. In the present study, we show that activated primary T cells express p53, which induces SAP expression. p53 is functional as a transcription factor in activated T cells and induces the expression of p21, PUMA and MDM2. PARP cleavage in the late phase of activation indicates that T cells expressing high levels of SAP undergo apoptosis. Modifying p53 levels using Nutlin-3, which specifically dissociates the MDM2-p53 interaction, was sufficient to upregulate SAP expression, indicating that SAP is a target of p53 in T cells. We also demonstrated p53's role as a transcription factor for SAP in activated T cells by ChIP assays. Our result suggests that p53 contributes to T cell homeostasis through the induction of the pro-apoptotic SAP. A high level of SAP is necessary for the activation-induced cell death that is pivotal in termination of the T cell response.

  20. DNA-mediated oxidation of p53.

    Science.gov (United States)

    Schaefer, Kathryn N; Barton, Jacqueline K

    2014-06-01

    Transcription factor p53 is the most commonly altered gene in human cancer. As a redox-active protein in direct contact with DNA, p53 can directly sense oxidative stress through DNA-mediated charge transport. Electron hole transport occurs over long distances through the π-stacked bases and leads to the oxidative dissociation of p53. The extent of protein dissociation depends upon the redox potential of the DNA in direct contact with each p53 monomer. The DNA sequence dependence of p53 oxidative dissociation was examined by electrophoretic mobility shift assays using oligonucleotides containing both synthetic and human p53 consensus sequences with an appended photooxidant, anthraquinone. Greater p53 dissociation is observed from sequences containing low-redox potential purine regions, particularly guanine triplets. Using denaturing polyacrylamide gel electrophoresis of irradiated anthraquinone-modified DNA, the DNA damage sites corresponding to sites of preferred electron hole localization were determined. The resulting DNA damage preferentially localizes to guanine doublets and triplets. Oxidative DNA damage is inhibited in the presence of p53, but only at sites in direct contact with p53. From these data, predictions about the sensitivity of human p53-binding sites to oxidative stress as well as possible biological implications have been made. On the basis of our data, the guanine pattern within the purine region of each p53-binding site determines the response of p53 to DNA oxidation, yielding for some sequences the oxidative dissociation of p53 from a distance and thereby providing another potential role for DNA charge transport chemistry within the cell. PMID:24853816