Sample records for chromium 53 target

  1. Reactor target from metal chromium for "pure" high-intensive artificial neutrino source (United States)

    Gavrin, V. N.; Kozlova, Yu. P.; Veretenkin, E. P.; Logachev, A. V.; Logacheva, A. I.; Lednev, I. S.; Okunkova, A. A.


    The paper presents the first results of development of manufacturing technology of metallic chromium targets from highly enriched isotope 50Cr for irradiation in a high flux nuclear reactor to obtain a compact high intensity neutrino source with low content of radionuclide impurities and minimum losses of enriched isotope. The main technological stages are the hydrolysis of chromyl fluoride, the electrochemical reduction of metallic chromium, the hot isostatic pressing of chromium powder and the electrical discharge machining of chromium bars. The technological stages of hot isostatic pressing of chromium powder and of electrical discharge machining of Cr rods have been tested.

  2. Chromium (United States)

    ... Intern Med 1991;115:917-24. Abraham AS, Brooks BA, Eylath U. The effects of chromium supplementation on serum glucose and lipids in patients with and without non-insulin-dependent diabetes. Metabolism 1992;41:768-71. Hermann J, Arquitt A. ...

  3. p53 as a target for the treatment of cancer. (United States)

    Duffy, Michael J; Synnott, Naoise C; McGowan, Patricia M; Crown, John; O'Connor, Darran; Gallagher, William M


    TP53 (p53) is the most frequently mutated gene in cancer, being altered in approximately 50% of human malignancies. In most, if not all, cancers lacking mutation, wild-type (WT) p53 is inactivated by interaction with cellular (MDM2/MDM4) or viral proteins, leading to its degradation. Because of its near universal alteration in cancer, p53 is an attractive target for the development of new targeted therapies for this disease. However, until recently, p53 was widely regarded as ‘‘undruggable’’. This situation has now changed, as several compounds have become available that can restore wild-type properties to mutant p53 (e.g., PRIMA-1 and PRIMA-1MET). Other compounds are available that prevent the binding of MDM2/MDM4 to WT p53, thereby blocking its degradation (e.g., nutlins). Anti-mutant p53 compounds are potentially most useful in cancers with a high prevalence of p53 mutations. These include difficult-totreat tumors such as high grade serous ovarian cancer, triple-negative breast cancer and squamous lung cancer. MDM2/4 antagonists, on the other hand, are likely to be efficacious in malignancies in which MDM2 or MDM4 is overexpressed such as sarcomas, neuroblastomas and specific childhood leukemias. Presently, early clinical trials are ongoing evaluating the anti-mutant p53 agent, PRIMA-1MET, and specific MDM2–p53 nutlin antagonists.

  4. Targeting cancer stem cells with p53 modulators (United States)

    Hayashi, Ryo; Appella, Ettore; Kopelovich, Levy; DeLeo, Albert B.


    Cancer stem cells (CSC) typically over-express aldehyde dehydrogenase (ALDH). Thus, ALDHbright tumor cells represent targets for developing novel cancer prevention/treatment interventions. Loss of p53 function is a common genetic event during cancer development wherein small molecular weight compounds (SMWC) that restore p53 function and reverse tumor growth have been identified. Here, we focused on two widely studied p53 SMWC, CP-31398 and PRIMA-1, to target ALDHbright CSC in human breast, endometrial and pancreas carcinoma cell lines expressing mutant or wild type (WT) p53. CP-31398 and PRIMA-1 significantly reduced CSC content and sphere formation by these cell lines in vitro. In addition, these agents were more effective in vitro against CSC compared to cisplatin and gemcitabine, two often-used chemotherapeutic agents. We also tested a combinatorial treatment in methylcholantrene (MCA)-treated mice consisting of p53 SMWC and p53-based vaccines. Yet using survival end-point analysis, no increased efficacy in the presence of either p53 SMWC alone or with vaccine compared to vaccine alone was observed. These results may be due, in part, to the presence of immune cells, such as activated lymphocytes expressing WT p53 at levels comparable to some tumor cells, wherein further increase of p53 expression by p53 SMWC may alter survival of these immune cells and negatively impact an effective immune response. Continuous exposure of mice to MCA may have also interfered with the action of these p53 SMWC, including potential direct interaction with MCA. Nonetheless, the effect of p53 SMWC on CSC and cancer treatment remains of great interest. PMID:27074569

  5. Methylation levels of P16 and TP53 that are involved in DNA strand breakage of 16HBE cells treated by hexavalent chromium. (United States)

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


    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.

  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


    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...

  7. Expression signature based on TP53 target genes doesn't predict response to TP53-MDM2 inhibitor in wild type TP53 tumors. (United States)

    Sonkin, Dmitriy


    A number of TP53-MDM2 inhibitors are currently under investigation as therapeutic agents in a variety of clinical trials in patients with TP53 wild type tumors. Not all wild type TP53 tumors are sensitive to such inhibitors. In an attempt to improve selection of patients with TP53 wild type tumors, an mRNA expression signature based on 13 TP53 transcriptional target genes was recently developed (Jeay et al. 2015). Careful reanalysis of TP53 status in the study validation data set of cancer cell lines considered to be TP53 wild type detected TP53 inactivating alterations in 23% of cell lines. The subsequent reanalysis of the remaining TP53 wild type cell lines clearly demonstrated that unfortunately the 13-gene signature cannot predict response to TP53-MDM2 inhibitor in TP53 wild type tumors.

  8. Targeting the p53 Pathway in Ewing Sarcoma


    Neilsen, Paul M.; Pishas, Kathleen I.; Callen, David F; Thomas, David M.


    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 downs...

  9. Immunological and Clinical Effects of Vaccines Targeting p53-Overexpressing Malignancies

    NARCIS (Netherlands)

    Vermeij, R.; Leffers, N.; van der Burg, S. H.; Melief, C. J.; Daemen, T.; Nijman, H. W.


    Approximately 50% of human malignancies carry p53 mutations, which makes it a potential antigenic target for cancer immunotherapy. Adoptive transfer with p53-specific cytotoxic T-lymphocytes (CTL) and CD4(+) T-helper cells eradicates p53-overexpressing tumors in mice. Furthermore, p53 antibodies and

  10. Long Noncoding RNA MEG3 Interacts with p53 Protein and Regulates Partial p53 Target Genes in Hepatoma Cells.

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    Juanjuan Zhu

    Full Text Available Maternally Expressed Gene 3 (MEG3 encodes a lncRNA which is suggested to function as a tumor suppressor. Previous studies suggested that MEG3 functioned through activation of p53, however, the functional properties of MEG3 remain obscure and their relevance to human diseases is under continuous investigation. Here, we try to illuminate the relationship of MEG3 and p53, and the consequence in hepatoma cells. We find that transfection of expression construct of MEG3 enhances stability and transcriptional activity of p53. Deletion analysis of MEG3 confirms that full length and intact structure of MEG3 are critical for it to activate p53-mediated transactivation. Interestingly, our results demonstrate for the first time that MEG3 can interact with p53 DNA binding domain and various p53 target genes are deregulated after overexpression of MEG3 in hepatoma cells. Furthermore, results of qRT-PCR have shown that MEG3 RNA is lost or reduced in the majority of HCC samples compared with adjacent non-tumorous samples. Ectopic expression of MEG3 in hepatoma cells significantly inhibits proliferation and induces apoptosis. In conclusion, our data demonstrates that MEG3 functions as a tumor suppressor in hepatoma cells through interacting with p53 protein to activate p53-mediated transcriptional activity and influence the expression of partial p53 target genes.

  11. Targeting the p53 Pathway in Ewing Sarcoma

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    Paul M. Neilsen


    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.

  12. Thick-target PIXE analysis of chromium, copper and arsenic impregnated lumber (United States)

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


    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.

  13. Necdin, a p53-target gene, is an inhibitor of p53-mediated growth arrest.

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    Julie Lafontaine

    Full Text Available In vitro, cellular immortalization and transformation define a model for multistep carcinogenesis and current ongoing challenges include the identification of specific molecular events associated with steps along this oncogenic pathway. Here, using NIH3T3 cells, we identified transcriptionally related events associated with the expression of Polyomavirus Large-T antigen (PyLT, a potent viral oncogene. We propose that a subset of these alterations in gene expression may be related to the early events that contribute to carcinogenesis. The proposed tumor suppressor Necdin, known to be regulated by p53, was within a group of genes that was consistently upregulated in the presence of PyLT. While Necdin is induced following p53 activation with different genotoxic stresses, Necdin induction by PyLT did not involve p53 activation or the Rb-binding site of PyLT. Necdin depletion by shRNA conferred a proliferative advantage to NIH3T3 and PyLT-expressing NIH3T3 (NIHLT cells. In contrast, our results demonstrate that although overexpression of Necdin induced a growth arrest in NIH3T3 and NIHLT cells, a growing population rapidly emerged from these arrested cells. This population no longer showed significant proliferation defects despite high Necdin expression. Moreover, we established that Necdin is a negative regulator of p53-mediated growth arrest induced by nutlin-3, suggesting that Necdin upregulation could contribute to the bypass of a p53-response in p53 wild type tumors. To support this, we characterized Necdin expression in low malignant potential ovarian cancer (LMP where p53 mutations rarely occur. Elevated levels of Necdin expression were observed in LMP when compared to aggressive serous ovarian cancers. We propose that in some contexts, the constitutive expression of Necdin could contribute to cancer promotion by delaying appropriate p53 responses and potentially promote genomic instability.

  14. Zn(II)-curc targets p53 in thyroid cancer cells. (United States)

    Garufi, Alessia; D'Orazi, Valerio; Crispini, Alessandra; D'Orazi, Gabriella


    TP53 mutation is a common event in many cancers, including thyroid carcinoma. Defective p53 activity promotes cancer resistance to therapies and a more malignant phenotype, acquiring oncogenic functions. Rescuing the function of mutant p53 (mutp53) protein is an attractive anticancer therapeutic strategy. Zn(II)-curc is a novel small molecule that has been shown to target mutp53 protein in several cancer cells, but its effect in thyroid cancer cells remains unclear. Here, we investigated whether Zn(II)-curc could affect p53 in thyroid cancer cells with both p53 mutation (R273H) and wild-type p53. Zn(II)-curc induced mutp53H273 downregulation and reactivation of wild-type functions, such as binding to canonical target promoters and target gene transactivation. This latter effect was similar to that induced by PRIMA-1. In addition, Zn(II)-curc triggered p53 target gene expression in wild-type p53-carrying cells. In combination treatments, Zn(II)-curc enhanced the antitumor activity of chemotherapeutic drugs, in both mutant and wild-type-carrying cancer cells. Taken together, our data indicate that Zn(II)-curc promotes the reactivation of p53 in thyroid cancer cells, providing in vitro evidence for a potential therapeutic approach in thyroid cancers.

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

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    Labhart Paul


    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.

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

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    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.

  17. Stimulation of autophagy by the p53 target gene Sestrin2. (United States)

    Maiuri, Maria Chiara; Malik, Shoaib Ahmad; Morselli, Eugenia; Kepp, Oliver; Criollo, Alfredo; Mouchel, Pierre-Luc; Carnuccio, Rosa; Kroemer, Guido


    The oncosuppressor protein p53 regulates autophagy in a dual fashion. The pool of cytoplasmic p53 protein represses autophagy in a transcription-independent fashion, while the pool of nuclear p53 stimulates autophagy through the transactivation of specific genes. Here we report the discovery that Sestrin2, a novel p53 target gene, is involved in the induction of autophagy. Depletion of Sestrin2 by RNA interference reduced the level of autophagy in a panel of p53-sufficient human cancer cell lines responding to distinct autophagy inducers. In quantitative terms, Sestrin2 depletion was as efficient in preventing autophagy induction as was the depletion of Dram, another p53 target gene. Knockout of either Sestrin2 or Dram reduced autophagy elicited by nutrient depletion, rapamycin, lithium or thapsigargin. Moreover, autophagy induction by nutrient depletion or pharmacological stimuli led to an increase in Sestrin2 expression levels in p53-proficient cells. In strict contrast, the depletion of Sestrin2 or Dram failed to affect autophagy in p53-deficient cells and did not modulate the inhibition of baseline autophagy by a cytoplasmic p53 mutant that was reintroduced into p53-deficient cells. We conclude that Sestrin2 acts as a positive regulator of autophagy in p53-proficient cells.

  18. MicroRNA-24 increases hepatocellular carcinoma cell metastasis and invasion by targeting p53: miR-24 targeted p53. (United States)

    Chen, Li; Luo, Liang; Chen, Wei; Xu, Hong-Xu; Chen, Fan; Chen, Lian-Zhou; Zeng, Wen-Tao; Chen, Jing-Song; Huang, Xiao-Hui


    MicroRNA-24 (miR-24), a member of the miRNA family, functions as an oncogene in various types of human cancer. However, the underlying mechanisms of miR-24 involvement in the development and progression of hepatocellular carcinoma (HCC) remain poorly understood. The present study revealed that miRNA-24 down-regulates p53 through binding to the 3'-UTR of p53 mRNA based on a luciferase reporter assay, and that the expression level of miR-24 could affect the invasion of HCC lines via p53. Down-regulation of p53 significantly attenuated the inhibitory effects of miR-24 knockdown on the invasion of HCC cells, suggesting that miR-24 could be a potential target for HCC treatment. Moreover, our results revealed that miR-24 expression was significantly increased in HCC metastatic tumor tissues compared with matched non-metastatic tumor tissues, and that the up-regulation of miR-24 was significantly associated with down-regulation of p53 in the HCC tissues. In conclusion, this study demonstrates that miR-24 functions as an oncogene in HCC, at least partly by promoting cell invasion through down-regulation of p53. Therefore, miR-24 may be a potential therapeutic target for treatment of HCC.

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

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    Jennifer J Jordan


    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.

  20. Long non-coding RNA NEAT1 is a transcriptional target of p53 and modulates p53-induced transactivation and tumor-suppressor function. (United States)

    Idogawa, Masashi; Ohashi, Tomoko; Sasaki, Yasushi; Nakase, Hiroshi; Tokino, Takashi


    p53 is one of the most important tumor suppressor genes and the direct transcriptional targets of p53 must be explored to elucidate its functional mechanisms. Thus far, the p53 targets that have been primarily studied are protein-coding genes. Our previous study revealed that several long non-coding RNAs (lncRNAs) are direct transcriptional targets of p53, and knockdown of specific lncRNAs modulates p53-induced apoptosis. In this study, analysis of next-generation chromatin immunoprecipitation-sequencing (ChIP-seq) data for p53 revealed that the lncRNA NEAT1 is a direct transcriptional target of p53. The suppression of NEAT1 induction by p53 attenuates the inhibitory effect of p53 on cancer cell growth and also modulates gene transactivation, including that of many lncRNAs. Furthermore, low expression of NEAT1 is related to poor prognosis in several cancers. These results indicate that the induction of NEAT1 expression contributes to the tumor-suppressor function of p53 and suggest that p53 and NEAT1 constitute a transcriptional network contributing to various biological functions and tumor suppression. This article is protected by copyright. All rights reserved.

  1. MDM4 is a rational target for treating breast cancers with mutant p53. (United States)

    Miranda, Panimaya Jeffreena; Buckley, Daniel; Raghu, Dinesh; Pang, Jia-Min B; Takano, Elena A; Vijayakumaran, Reshma; Teunisse, Amina Fas; Posner, Atara; Procter, Tahlia; Herold, Marco J; Gamell, Cristina; Marine, Jean-Christophe; Fox, Stephen B; Jochemsen, Aart; Haupt, Sue; Haupt, Ygal


    Mutation of the key tumour suppressor p53 defines a transition in the progression towards aggressive and metastatic breast cancer (BC) with the poorest outcome. Specifically, the p53 mutation frequency exceeds 50% in triple-negative BC. Key regulators of mutant p53 that facilitate its oncogenic functions are potential therapeutic targets. We report here that the MDM4 protein is frequently abundant in the context of mutant p53 in basal-like BC samples. Importantly, we show that MDM4 plays a critical role in the proliferation of these BC cells. We demonstrate that conditional knockdown (KD) of MDM4 provokes growth inhibition across a range of BC subtypes with mutant p53, including luminal, Her2(+) and triple-negative BCs. In vivo, MDM4 was shown to be crucial for the establishment and progression of tumours. This growth inhibition was mediated, at least in part, by the cell cycle inhibitor p27. Depletion of p27 together with MDM4 KD led to recovery of the proliferative capacity of cells that were growth-inhibited by MDM4 KD alone. Consistently, we identified low levels of p27 expression in basal-like tumours corresponding to high levels of MDM4 and p53. This predicts a signature for a subset of tumours that may be amenable to therapies targeted towards MDM4 and mutant p53. The therapeutic potential of MDM4 as a target in BC with mutant p53 was shown in vitro by use of a small-molecule inhibitor. Overall, our study supports MDM4 as a novel therapeutic target for BC expressing mutant p53. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  2. The p53 network as therapeutic target in gastroenteropancreatic neuroendocrine neoplasms. (United States)

    Briest, Franziska; Grabowski, Patricia


    Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogeneous and especially the midgut tumors currently lack effective therapy options. Actionable driver mutations as therapeutic targets are rare. Subtype specific data concerning regulatory mechanisms or epigenetic aberrations are necessary for novel clinical trials. Although the p53 protein itself is rarely mutated in GEP-NENs, epigenetic and regulatory aberrations interfere with the p53 network activity and might function as s target for novel therapeutic approaches. In this review we analyze the current knowledge about the p53 network in GEP-NENs and discuss three possible strategies that include recovering p53 function, enforcing apoptosis by genotoxic stress induction and restoring silenced gene function, based on in vitro, in vivo and clinical data.

  3. Novel Roles for P53 in the Genesis and Targeting of Tetraploid Cancer Cells


    Batzaya Davaadelger; Hong Shen; Maki, Carl G.


    Tetraploid (4N) cells are considered important in cancer because they can display increased tumorigenicity, resistance to conventional therapies, and are believed to be precursors to whole chromosome aneuploidy. It is therefore important to determine how tetraploid cancer cells arise, and how to target them. P53 is a tumor suppressor protein and key regulator of tetraploidy. As part of the "tetraploidy checkpoint", p53 inhibits tetraploid cell proliferation by promoting a G1-arrest in incipie...

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

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    Zhang Xifeng


    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. PRIMA-1Met suppresses colorectal cancer independent of p53 by targeting MEK. (United States)

    Lu, Tao; Zou, Yanmei; Xu, Guogang; Potter, Jane A; Taylor, Garry L; Duan, Qiuhong; Yang, Qin; Xiong, Huihua; Qiu, Hong; Ye, Dawei; Zhang, Peng; Yu, Shiying; Yuan, Xianglin; Zhu, Feng; Wang, Yihua; Xiong, Hua


    PRIMA-1Met is the methylated PRIMA-1 (p53 reactivation and induction of massive apoptosis) and could restore tumor suppressor function of mutant p53 and induce p53 dependent apoptosis in cancer cells harboring mutant p53. However, p53 independent activity of PRIMA-1Met remains elusive. Here we reported that PRIMA-1Met attenuated colorectal cancer cell growth irrespective of p53 status. Kinase profiling revealed that mitogen-activated or extracellular signal-related protein kinase (MEK) might be a potential target of PRIMA-1Met. Pull-down binding and ATP competitive assay showed that PRIMA-1Met directly bound MEK in vitro and in cells. Furthermore, the direct binding sites of PRIMA-1Met were explored by using a computational docking model. Treatment of colorectal cancer cells with PRIMA-1Met inhibited p53-independent phosphorylation of MEK, which in turn impaired anchorage-independent cell growth in vitro. Moreover, PRIMA-1Met suppressed colorectal cancer growth in xenograft mouse model by inhibiting MEK1 activity.Taken together, our findings demonstrate a novel p53-independent activity of PRIMA-1Met to inhibit MEK and suppress colorectal cancer growth.

  6. TP53 Alterations Correlate with Response to VEGF/VEGFR Inhibitors: Implications for Targeted Therapeutics. (United States)

    Wheler, Jennifer J; Janku, Filip; Naing, Aung; Li, Yali; Stephen, Bettzy; Zinner, Ralph; Subbiah, Vivek; Fu, Siqing; Karp, Daniel; Falchook, Gerald S; Tsimberidou, Apostolia M; Piha-Paul, Sarina; Anderson, Roosevelt; Ke, Danxia; Miller, Vincent; Yelensky, Roman; Lee, J Jack; Hong, David; Kurzrock, Razelle


    TP53 tumor-suppressor gene mutations are among the most frequent abnormalities in cancer, affecting approximately 40% of patients. Yet, there is no accepted way to target these alterations in the clinic. At the same time, antagonists of VEGFR or its ligand are best-selling oncology drugs, with multiple, expensive compounds approved. Although only a subset of patients benefit from these antiangiogenesis agents, no relevant biomarker has been identified. Interestingly, TP53 mutations upregulate VEGF-A and VEGFR2. We prospectively enrolled 500 patients, to be interrogated by comprehensive genomic profiling (CGP) (next-generation sequencing, 236 genes), and to be matched, whenever possible, with targeted agents. Herein, we analyze outcomes based on VEGF/VEGFR inhibitor treatment and presence of TP53 mutations. Of the 500 patients, 188 (37.6%; with ≥1 alteration) were treated; 106 (56% of 188) had tumors that harbored TP53 mutations. VEGF/VEGFR inhibitor therapy was independently associated with improvement in all outcome parameters [rate of stable disease (SD) ≥6 months/partial and complete remission (PR/CR); (31% versus 7%; TP53-mutant patients (who received no other molecular-matched agents) treated with versus without VEGF/VEGFR inhibitors), time-to-treatment failure, and overall survival (multivariate analysis: all P ≤ 0.01)] for the patients harboring TP53-mutant cancers, but improvement was not seen in any of these parameters for patients with TP53 wild-type neoplasms. We conclude that TP53 mutations predict sensitivity to VEGF/VEGFR inhibitors in the clinic. TP53 alterations may therefore be a ready biomarker for treatment with antiangiogenesis agents, a finding of seminal importance across the cancer field. Mol Cancer Ther; 15(10); 2475-85. ©2016 AACR.

  7. Novel roles for p53 in the genesis and targeting of tetraploid cancer cells. (United States)

    Davaadelger, Batzaya; Shen, Hong; Maki, Carl G


    Tetraploid (4N) cells are considered important in cancer because they can display increased tumorigenicity, resistance to conventional therapies, and are believed to be precursors to whole chromosome aneuploidy. It is therefore important to determine how tetraploid cancer cells arise, and how to target them. P53 is a tumor suppressor protein and key regulator of tetraploidy. As part of the "tetraploidy checkpoint", p53 inhibits tetraploid cell proliferation by promoting a G1-arrest in incipient tetraploid cells (referred to as a tetraploid G1 arrest). Nutlin-3a is a preclinical drug that stabilizes p53 by blocking the interaction between p53 and MDM2. In the current study, Nutlin-3a promoted a p53-dependent tetraploid G1 arrest in two diploid clones of the HCT116 colon cancer cell line. Both clones underwent endoreduplication after Nutlin removal, giving rise to stable tetraploid clones that showed increased resistance to ionizing radiation (IR) and cisplatin (CP)-induced apoptosis compared to their diploid precursors. These findings demonstrate that transient p53 activation by Nutlin can promote tetraploid cell formation from diploid precursors, and the resulting tetraploid cells are therapy (IR/CP) resistant. Importantly, the tetraploid clones selected after Nutlin treatment expressed approximately twice as much P53 and MDM2 mRNA as diploid precursors, expressed approximately twice as many p53-MDM2 protein complexes (by co-immunoprecipitation), and were more susceptible to p53-dependent apoptosis and growth arrest induced by Nutlin. Based on these findings, we propose that p53 plays novel roles in both the formation and targeting of tetraploid cells. Specifically, we propose that 1) transient p53 activation can promote a tetraploid-G1 arrest and, as a result, may inadvertently promote formation of therapy-resistant tetraploid cells, and 2) therapy-resistant tetraploid cells, by virtue of having higher P53 gene copy number and expressing twice as many p53-MDM2

  8. Stress-responsive sestrins link p53 with redox regulation and mammalian target of rapamycin signaling. (United States)

    Budanov, Andrei V


    The tumor suppressor p53 protects organisms from most types of cancer through multiple mechanisms. The p53 gene encodes a stress-activated transcriptional factor that transcriptionally regulates a large set of genes with versatile functions. These p53-activated genes mitigate consequences of stress regulating cell viability, growth, proliferation, repair, and metabolism. Recently, we described a novel antioxidant function of p53, which is important for its tumor suppressor activity. Among the many antioxidant genes activated by p53, Sestrins (Sesns) are critical for suppression of reactive oxygen species (ROS) and protection from oxidative stress, transformation, and genomic instability. Sestrins can regulate ROS through their direct effect on antioxidant peroxiredoxin proteins and through the AMP-activated protein kinase-target of rapamycin signaling pathway. The AMP-activated protein kinase-target of rapamycin axis is critical for regulation of metabolism and autophagy, two processes associated with ROS production, and deregulation of this pathway increases vulnerability of the organism to stress, aging, and age-related diseases, including cancer. Recently, we have shown that inactivation of Sestrin in fly causes accumulation of age-associated damage. Hence, Sestrins can link p53 with aging and age-related diseases.

  9. 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.

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



    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....

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


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


    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...

  12. Homozygous mdm2 SNP309 cancer cells with compromised transcriptional elongation at p53 target genes are sensitive to induction of p53-independent cell death. (United States)

    Rosso, Melissa; Polotskaia, Alla; Bargonetti, Jill


    A single nucleotide polymorphism (T to G) in the mdm2 P2 promoter, mdm2 SNP309, leads to MDM2 overexpression promoting chemotherapy resistant cancers. Two mdm2 G/G SNP309 cancer cell lines, MANCA and A875, have compromised wild-type p53 that co-localizes with MDM2 on chromatin. We hypothesized that MDM2 in these cells inhibited transcription initiation at the p53 target genes p21 and puma. Surprisingly, following etoposide treatment transcription initiation occurred at the compromised target genes in MANCA and A875 cells similar to the T/T ML-1 cell line. In all cell lines tested there was equally robust recruitment of total and initiated RNA polymerase II (Pol II). We found that knockdown of MDM2 in G/G cells moderately increased expression of subsets of p53 target genes without increasing p53 stability. Importantly, etoposide and actinomycin D treatments increased histone H3K36 trimethylation in T/T, but not G/G cells, suggesting a G/G correlated inhibition of transcription elongation. We therefore tested a chemotherapeutic agent (8-amino-adenosine) that induces p53-independent cell death for higher clinically relevant cytotoxicity. We demonstrated that T/T and G/G mdm2 SNP309 cells were equally sensitive to 8-amino-adenosine induced cell death. In conclusion for cancer cells overexpressing MDM2, targeting MDM2 may be less effective than inducing p53-independent cell death.

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

    Directory of Open Access Journals (Sweden)

    Iva Simeonova


    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.

  14. TRIAD1 Is a Novel Transcriptional Target of p53 and Regulates Nutlin-3a-Induced Cell Death. (United States)

    Lee, Junwoo; An, Sungkwan; Choi, Yeong Min; Jung, Jin Hyuk; Li, Li; Meng, Hong; Dong, Yinmao; Ahn, Kyu Joong; An, In-Sook; Bae, Seunghee


    Nutlin-3a is a non-genotoxic, p53-activating, MDM2 inhibitor being investigated as an anticancer agent. Although Nutlin-3a selectively antagonizes the ubiquitin E3 ligase activity of MDM2, its efficacy is not entirely regulated by MDM2 levels in cancer cells. Here, we report that the cytotoxic effects of Nutlin-3a are regulated by TRIAD1 via a positive feedback loop with p53. We found that Nutlin-3a enhanced TRIAD1 transcription in a p53-dependent manner. Using in silico analysis and promoter luciferase assays, we demonstrated that p53-mediated transcription of TRIAD1 is mediated by a p53 consensus sequence in the TRIAD1 promoter region. Silencing TRIAD1 expression in wild-type p53 (p53(WT) ) cancer cells suppressed Nutlin-3a-mediated p53 activation and p53 target gene expression. These effects were enhanced in TRIAD1-overexpressing p53(WT) cancer cells, but not in p53-deficient cancer cells. Furthermore, TRIAD1 knockdown significantly reduced the growth inhibitory and cytotoxic effects of Nutlin-3a in p53(WT) cancer cells, as demonstrated by cell viability assays, cell cycle analysis, clonogenic growth, and soft-agar colony forming assays. Together, these data indicate that TRIAD1 regulates Nutlin-3a-mediated p53 activation and the cytotoxic activity of Nutlin-3a. J. Cell. Biochem. 9999: 1-8, 2016. © 2016 Wiley Periodicals, Inc.

  15. Identification, validation, and targeting of the mutant p53-PARP-MCM chromatin axis in triple negative breast cancer. (United States)

    Qiu, Wei-Gang; Polotskaia, Alla; Xiao, Gu; Di, Lia; Zhao, Yuhan; Hu, Wenwei; Philip, John; Hendrickson, Ronald C; Bargonetti, Jill


    Over 80% of triple negative breast cancers express mutant p53. Mutant p53 often gains oncogenic function suggesting that triple negative breast cancers may be driven by p53 protein type. To determine the chromatin targets of this gain-of-function mutant p53 we used inducible knockdown of endogenous gain-of-function mtp53 in MDA-MB-468 cells in conjunction with stable isotope labeling with amino acids in cell culture and subcellular fractionation. We sequenced over 70,000 total peptides for each corresponding reciprocal data set and were able to identify 3010 unique cytoplasmic fraction proteins and 3403 unique chromatin fraction proteins. The present proteomics experiment corroborated our previous experiment-based results that poly ADP-ribose polymerase has a positive association with mutant p53 on the chromatin. Here, for the first time we report that the heterohexomeric minichromosome maintenance complex that participates in DNA replication initiation ranked as a high mutant p53-chromatin associated pathway. Enrichment analysis identified the minichromosome maintenance members 2-7. To validate this mutant p53- poly ADP-ribose polymerase-minichromosome maintenance functional axis, we experimentally depleted R273H mutant p53 and found a large reduction of the amount of minichromosome maintenance complex proteins on the chromatin. Furthermore a mutant p53-minichromosome maintenance 2 direct interaction was detected. Overexpressed mutant p53, but not wild type p53, showed a protein-protein interaction with minichromosome maintenance 2 and minichromosome maintenance 4. To target the mutant p53- poly ADP-ribose polymerase-minichromosome maintenance axis we treated cells with the poly ADP-ribose polymerase inhibitor talazoparib and the alkylating agent temozolomide and detected synergistic activation of apoptosis only in the presence of mutant p53. Furthermore when minichromosome maintenance 2-7 activity was inhibited the synergistic activation of apoptosis was blocked

  16. Targeting the ∆133p53 isoform can restore chemosensitivity in 5-fluorouracil-resistant cholangiocarcinoma cells. (United States)

    Nutthasirikul, Nichapavee; Hahnvajanawong, Chariya; Techasen, Anchalee; Limpaiboon, Temduang; Leelayuwat, Chanvit; Chau-In, Siri; Jearanaikoon, Patcharee


    Lack of the normal p53 transactivation domain, ∆133p53 isoform exhibits anti-p53 function. Many studies report the correlation between ∆133p53 expression and poor survival in various cancers, including cholangiocarcinoma (CCA), which is a cancer of the bile ducts. CCA almost always results in short survival times. The relevance of ∆133p53 to drug resistance in CCA is not yet well understood. This study aimed to demonstrate the association between ∆133p53 and 5-fluorouracil (5-FU) resistance in CCA. ∆133p53 protein was highly expressed in CCA patients with poor outcome compared to favorable outcome but was not statistically significant. However, a significant correlation was found between normalized ∆133p53 levels and 5-FU resistance which was defined by an ex vivo histoculture drug response assay (P=0.019). Two stable 5-FU-resistant CCA cell lines, KKU-M139R (IC50 38.8 µM) and KKU-M214R (IC50 39.5 µM), were used as a model to evaluate the role of ∆133p53. Increased ∆133p53 was correlated with 5-FU in a dose-dependent manner. The transient knockdown of ∆133p53 expression can restore drug sensitivity in both resistant CCA cells with 11- to 45-fold reduction of IC50 compared to control. Upon ∆133p53 silencing, apoptotic signaling was enhanced by the upregulation of Bax and downregulation of Bcl-2. Additionally, p21 and p27 were upregulated, resulting in cell cycle arrest at G2. Inhibition of colony formation and prolong doubling time were also observed. Our findings demonstrated that chemosensitivity can be modulated via targeting of ∆133p53 suggesting the potential use of ∆133p53 as a candidate for targeting therapy in CCA.

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


    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

  18. WRAP53 is essential for Cajal body formation and for targeting the survival of motor neuron complex to Cajal bodies. (United States)

    Mahmoudi, Salah; Henriksson, Sofia; Weibrecht, Irene; Smith, Stephen; Söderberg, Ola; Strömblad, Staffan; Wiman, Klas G; Farnebo, Marianne


    The WRAP53 gene gives rise to a p53 antisense transcript that regulates p53. This gene also encodes a protein that directs small Cajal body-specific RNAs to Cajal bodies. Cajal bodies are nuclear organelles involved in diverse functions such as processing ribonucleoproteins important for splicing. Here we identify the WRAP53 protein as an essential factor for Cajal body maintenance and for directing the survival of motor neuron (SMN) complex to Cajal bodies. By RNA interference and immunofluorescence we show that Cajal bodies collapse without WRAP53 and that new Cajal bodies cannot be formed. By immunoprecipitation we find that WRAP53 associates with the Cajal body marker coilin, the splicing regulatory protein SMN, and the nuclear import receptor importinβ, and that WRAP53 is essential for complex formation between SMN-coilin and SMN-importinβ. Furthermore, depletion of WRAP53 leads to accumulation of SMN in the cytoplasm and prevents the SMN complex from reaching Cajal bodies. Thus, WRAP53 mediates the interaction between SMN and associated proteins, which is important for nuclear targeting of SMN and the subsequent localization of the SMN complex to Cajal bodies. Moreover, we detect reduced WRAP53-SMN binding in patients with spinal muscular atrophy, which is the leading genetic cause of infant mortality worldwide, caused by mutations in SMN1. This suggests that loss of WRAP53-mediated SMN trafficking contributes to spinal muscular atrophy.

  19. WRAP53 is essential for Cajal body formation and for targeting the survival of motor neuron complex to Cajal bodies.

    Directory of Open Access Journals (Sweden)

    Salah Mahmoudi

    Full Text Available The WRAP53 gene gives rise to a p53 antisense transcript that regulates p53. This gene also encodes a protein that directs small Cajal body-specific RNAs to Cajal bodies. Cajal bodies are nuclear organelles involved in diverse functions such as processing ribonucleoproteins important for splicing. Here we identify the WRAP53 protein as an essential factor for Cajal body maintenance and for directing the survival of motor neuron (SMN complex to Cajal bodies. By RNA interference and immunofluorescence we show that Cajal bodies collapse without WRAP53 and that new Cajal bodies cannot be formed. By immunoprecipitation we find that WRAP53 associates with the Cajal body marker coilin, the splicing regulatory protein SMN, and the nuclear import receptor importinβ, and that WRAP53 is essential for complex formation between SMN-coilin and SMN-importinβ. Furthermore, depletion of WRAP53 leads to accumulation of SMN in the cytoplasm and prevents the SMN complex from reaching Cajal bodies. Thus, WRAP53 mediates the interaction between SMN and associated proteins, which is important for nuclear targeting of SMN and the subsequent localization of the SMN complex to Cajal bodies. Moreover, we detect reduced WRAP53-SMN binding in patients with spinal muscular atrophy, which is the leading genetic cause of infant mortality worldwide, caused by mutations in SMN1. This suggests that loss of WRAP53-mediated SMN trafficking contributes to spinal muscular atrophy.

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



    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...

  1. Mechanistic validation of a clinical lead stapled peptide that reactivates p53 by dual HDM2 and HDMX targeting. (United States)

    Wachter, F; Morgan, A M; Godes, M; Mourtada, R; Bird, G H; Walensky, L D


    Hydrocarbon-stapled peptides that display key residues of the p53 transactivation domain have emerged as bona fide clinical candidates for reactivating the tumor suppression function of p53 in cancer by dual targeting of the negative regulators HDM2 and HDMX. A recent study questioned the mechanistic specificity of such stapled peptides based on interrogating their capacity to disrupt p53/HDM2 and p53/HDMX complexes in living cells using a new recombinase enhanced bimolecular luciferase complementation platform (ReBiL). Here, we directly evaluate the cellular uptake, intracellular targeting selectivity and p53-dependent cytotoxicity of the clinical prototype ATSP-7041. We find that under standard serum-containing tissue culture conditions, ATSP-7041 achieves intracellular access without membrane disruption, dose-dependently dissociates both p53/HDM2 and p53/HDMX complexes but not an unrelated protein complex in long-term ReBiL experiments, and is selectively cytotoxic to cancer cells bearing wild-type p53 by inducing a surge in p53 protein level. These studies underscore the importance of a thorough stepwise approach, including consideration of the time-dependence of cellular uptake and intracellular distribution, in evaluating and advancing stapled peptides for clinical translation.Oncogene advance online publication, 10 October 2016; doi:10.1038/onc.2016.361.

  2. LC-MS/MS-based targeted proteomics quantitatively detects the interaction between p53 and MDM2 in breast cancer. (United States)

    Zhang, Wen; Zhong, Ting; Chen, Yun


    In breast cancer, p53 could be functionally compromised by interaction with several proteins. Among those proteins, MDM2 serves as a pivotal negative regulator and counteracts p53 activation. Thus, the ability to quantitatively and accurately monitor the changes in level of p53-MDM2 interaction with disease state can enable an improved understanding of this protein-protein interaction (PPI), provide a better insight into cancer development and allow the emergence of advanced treatments. However, rare studies have evaluated the quantitative extent of PPI including p53-MDM2 interaction so far. In this study, a LC-MS/MS-based targeted proteomics assay was developed and coupled with co-immunoprecipitation (Co-IP) for the quantification of p53-MDM2 complex. A p53 antibody with the epitope residing at 156-214 residues achieved the greatest IP efficiency. 321KPLDGEYFTLQIR333 (p53) and 327ENWLPEDK334 (MDM2) were selected as surrogate peptides in the targeted analysis. Stable isotope-labeled synthetic peptides were used as internal standards. An LOQ (limit of quantification) of 2ng/mL was obtained. Then, the assay was applied to quantitatively detect total p53, total MDM2 and p53-MDM2 in breast cells and tissue samples. Western blotting was performed for a comparison. Finally, a quantitative time-course analysis in MCF-7 cells with the treatment of nutlin-3 as a PPI inhibitor was also monitored.

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


    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.

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

  5. p53, SKP2 and DKK3 as MYCN target genes and their potential therapeutic significance

    Directory of Open Access Journals (Sweden)

    Lindi eChen


    Full Text Available Neuroblastoma is the most common extracranial solid tumour of childhood. Despite significant advances, it currently still remains one of the most difficult childhood cancers to cure, with less than 40% of patients with high-risk disease being long-term survivors. MYCN is a proto-oncogene implicated to be directly involved in neuroblastoma development. Amplification of MYCN is associated with rapid tumour progression and poor prognosis. Novel therapeutic strategies which can improve the survival rates whilst reducing the toxicity in these patients are therefore required. Here we discuss genes regulated by MYCN in neuroblastoma, with particular reference to p53, SKP2 and DKK3 and strategies that may be employed to target them.

  6. Mutant p53: a novel target for the treatment of patients with triple-negative breast cancer? (United States)

    Synnott, N C; Murray, A; McGowan, P M; Kiely, M; Kiely, P A; O'Donovan, N; O'Connor, D P; Gallagher, W M; Crown, J; Duffy, M J


    The identification and validation of a targeted therapy for patients with triple-negative breast cancer (TNBC) is currently one of the most urgent needs in breast cancer therapeutics. One of the key reasons for the failure to develop a new therapy for this subgroup of breast cancer patients has been the difficulty in identifying a highly prevalent, targetable molecular alteration in these tumors. Recently however, the p53 gene was found to be mutated in approximately 80% of basal/TNBC, raising the possibility that targeting the mutant p53 protein product might be a new approach for the treatment of this form of breast cancer. In this study, we investigated the anti-cancer activity of PRIMA-1 and PRIMA-1(MET) (APR-246), two compounds which were previously reported to reactivate mutant p53 and convert it to a form with wild-type (WT) properties. Using a panel of 18 breast cancer cell lines and 2 immortalized breast cell lines, inhibition of proliferation by PRIMA-1 and PRIMA-1(MET) was found to be cell-line dependent, but independent of cell line molecular subtype. Although response was independent of molecular subtype, p53 mutated cell lines were significantly more sensitive to PRIMA-1(MET) than p53 WT cells (p = 0.029). Furthermore, response (measured as IC50 value) correlated significantly with p53 protein level as measured by ELISA (p = 0.0089, r=-0.57, n = 19). In addition to inhibiting cell proliferation, PRIMA-1(MET) induced apoptosis and inhibited migration in a p53 mutant-dependent manner. Based on our data, we conclude that targeting mutant p53 with PRIMA-1(MET) is a potential new approach for treating p53-mutated breast cancer, including the subgroup with triple-negative (TN) disease.

  7. Repair of Damaged M-Chromium-Aluminum-Yttrium Coatings Targeting Petroleum Industry Applications (United States)

    Farhat, Rabab

    The increase in efficiency of furnace and refinery components in petroleum industries has been the target of many studies. However, the repair technology for damaged pieces is still to be developed. During prolonged service, a degradation of developed coatings occurs as a result of the harsh environment. Therefore, a repair technology, which can extend the life of the coatings, is now under consideration. In this work, electrospark deposition (ESD) has been investigated to understand the solidification behavior and its possibility to repair damaged MCrAlY coatings. Ni-based alloys with different compositions were deposited on Ni substrate using ESD to understand crystal structure of the solidified deposit and the effect of the dissimilar weld composition on dilution. The electrode samples were prepared by spark plasma sintering (SPS). Firstly, different coatings with single and bi-phase microstructure were deposited on pure Ni substrate. Secondly, NiCoCrAlY and CoNiCrAlY were deposited on the damaged spot of the oxidized NiCoCrAlY and CoNiCrAlY respectively. A fine microstructure of metastable phases obtained from each deposit. Also, it was found that an epitaxial growth of NiCoCrAlY and CoNiCrAlY were obtained on the damaged spots. In addition, α-Al 2O3 was obtained on the surface of the deposit after 24hr oxidation at 1000°C.

  8. Identification, validation, and targeting of the mutant p53-PARP-MCM chromatin axis in triple negative breast cancer (United States)

    Qiu, Wei-Gang; Polotskaia, Alla; Xiao, Gu; Di, Lia; Zhao, Yuhan; Hu, Wenwei; Philip, John; Hendrickson, Ronald C.; Bargonetti, Jill


    Over 80% of triple negative breast cancers express mutant p53. Mutant p53 often gains oncogenic function suggesting that triple negative breast cancers may be driven by p53 protein type. To determine the chromatin targets of this gain-of-function mutant p53 we used inducible knockdown of endogenous gain-of-function mtp53 in MDA-MB-468 cells in conjunction with stable isotope labeling with amino acids in cell culture and subcellular fractionation. We sequenced over 70,000 total peptides for each corresponding reciprocal data set and were able to identify 3010 unique cytoplasmic fraction proteins and 3403 unique chromatin fraction proteins. The present proteomics experiment corroborated our previous experiment-based results that poly ADP-ribose polymerase has a positive association with mutant p53 on the chromatin. Here, for the first time we report that the heterohexomeric minichromosome maintenance complex that participates in DNA replication initiation ranked as a high mutant p53-chromatin associated pathway. Enrichment analysis identified the minichromosome maintenance members 2–7. To validate this mutant p53- poly ADP-ribose polymerase-minichromosome maintenance functional axis, we experimentally depleted R273H mutant p53 and found a large reduction of the amount of minichromosome maintenance complex proteins on the chromatin. Furthermore a mutant p53-minichromosome maintenance 2 direct interaction was detected. Overexpressed mutant p53, but not wild type p53, showed a protein-protein interaction with minichromosome maintenance 2 and minichromosome maintenance 4. To target the mutant p53- poly ADP-ribose polymerase-minichromosome maintenance axis we treated cells with the poly ADP-ribose polymerase inhibitor talazoparib and the alkylating agent temozolomide and detected synergistic activation of apoptosis only in the presence of mutant p53. Furthermore when minichromosome maintenance 2–7 activity was inhibited the synergistic activation of apoptosis was

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


    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.

  10. Identification of Semaphorin3B as a Direct Target of p53

    Directory of Open Access Journals (Sweden)

    Kensuke Ochi


    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.

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

    NARCIS (Netherlands)

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


    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

  12. SIRT inhibitors induce cell death and p53 acetylation through targeting both SIRT1 and SIRT2. (United States)

    Peck, Barrie; Chen, Chun-Yuan; Ho, Ka-Kei; Di Fruscia, Paolo; Myatt, Stephen S; Coombes, R Charles; Fuchter, Matthew J; Hsiao, Chwan-Deng; Lam, Eric W-F


    SIRT proteins play an important role in the survival and drug resistance of tumor cells, especially during chemotherapy. In this study, we investigated the potency, specificity, and cellular targets of three SIRT inhibitors, Sirtinol, Salermide, and EX527. Cell proliferative and cell cycle analyses showed that Sirtinol and Salermide, but not EX527, were effective in inducing cell death at concentrations of 50 micromol/L or over in MCF-7 cells. Instead, EX527 caused cell cycle arrest at G(1) at comparable concentrations. In vitro SIRT assays using a p53 peptide substrate showed that all three compounds are potent SIRT1/2 inhibitors, with EX527 having the highest inhibitory activity for SIRT1. Computational docking analysis showed that Sirtinol and Salermide have high degrees of selectivity for SIRT1/2, whereas EX527 has high specificity for SIRT1 but not SIRT2. Consistently, Sirtinol and Salermide, but not EX527, treatment resulted in the in vivo acetylation of the SIRT1/2 target p53 and SIRT2 target tubulin in MCF-7 cells, suggesting that EX527 is ineffective in inhibiting SIRT2 and that p53 mediates the cytotoxic function of Sirtinol and Salermide. Studies using breast carcinoma cell lines and p53-deficient mouse fibroblasts confirmed that p53 is essential for the Sirtinol and Salermide-induced apoptosis. Further, we showed using small interfering RNA that silencing both SIRTs, but not SIRT1 and SIRT2 individually, can induce cell death in MCF-7 cells. Together, our results identify the specificity and cellular targets of these novel inhibitors and suggest that SIRT inhibitors require combined targeting of both SIRT1 and SIRT2 to induce p53 acetylation and cell death. Mol Cancer Ther; 9(4); 844-55. (c)2010 AACR.

  13. The tumor suppressor p53 regulates autophagosomal and lysosomal biogenesis in lung cancer cells by targeting transcription factor EB. (United States)

    Zhang, Zengli; Wang, Hongfeng; Ding, Qifeng; Xing, Yufei; Xu, Delai; Xu, Zhonghua; Zhou, Tong; Qian, Bin; Ji, Chenghong; Pan, Xue; Zhong, Anyuan; Ying, Zheng; Zhou, Caicun; Shi, Minhua


    The cellular protein degradation system, such as proteasomal or autophagy-lysosomal system plays an important role in the pathogenesis of a variety of human diseases including cancer. Transcription factor EB (TFEB) is a master transcriptional factor in the regulation of autophagy-lysosome pathway (ALP), and it has multiple biological functions including protein degradation, cell homeostasis and cell survival. In the present study we show that the tumor suppressor p53 can regulate TFEB nuclear translocation and activity in lung cancer cells. We found p53 deletion or chemical inhibition of p53 using pifithrin-α could promote the translocation of TFEB from cytoplasm to the nucleus, thus increased the TFEB-mediated lysosomal and autophagosomal biogenesis in lung cancer cells. Moreover, re-expression of p53 could decrease the expression levels of TFEB-targeting genes involved in ALP, and knockdown of TFEB could abolish the effect of p53 on the regulation of ALP gene expression. Taken together, our data indicate that p53 affects ALP through regulating TFEB nuclear translocation in lung cancer cells. Importantly, our study reveals a critical link between two keys factors in tumourigenesis and autophagy, and suggests a potential important role of p53-TFEB signaling axis in lung cancer.

  14. Targeting p53-deficient chronic lymphocytic leukemia cells in vitro and in vivo by ROS-mediated mechanism. (United States)

    Liu, Jinyun; Chen, Gang; Pelicano, Helene; Liao, Jianwei; Huang, Jie; Feng, Li; Keating, Michael J; Huang, Peng


    Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries. Loss of p53 function in CLL cells due to chromosome 17p deletion or p53 mutations often leads to a more malignant disease phenotype and is associated with drug resistance and poor clinical outcome. Thus, development of novel therapeutic strategies to effectively target CLL cells with p53 deficiency is clinically important. Here we showed that p53-null CLL cells were highly sensitive to ROS-mediated cell killing due to their intrinsic ROS stress. We further demonstrated that a natural compound phenethyl isothiocyanate (PEITC) was able to effectively kill CLL cells with loss of p53, even under the protection of stromal cells. In p53-defficient CLL cells, PEITC induced a rapid depletion of glutathione and a severe accumulation of ROS, leading to massive leukemia cell death in the stromal microenvironment. The drug-induced cell death was associated with a significant decrease of in MCL-1 survival molecule. We further showed that ROS-mediated cell death was the key mechanism by which PEITC induced cytotoxicity, since such cell death could be prevented by addition of antioxidant NAC. Importantly, in vivo study showed that PEITC was able to induce substantial leukemia cell death in mice. Treatment of CLL mice harboring TCL1-Tg:p53-/- genotype with PEITC significantly prolonged the median survival time of the animals. Our study identifies a vulnerability of p53-null CLL cells with high sensitivity to ROS-generating agents, and suggests that PEITC may potentially be useful for clinical treatment of CLL with 17p deletion and p53 mutations.

  15. Anchoring Intrinsically Disordered Proteins to Multiple Targets: Lessons from N-Terminus of the p53 Protein

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    Yongqi Huang


    Full Text Available Anchor residues, which are deeply buried upon binding, play an important role in protein–protein interactions by providing recognition specificity and facilitating the binding kinetics. Up to now, studies on anchor residues have been focused mainly on ordered proteins. In this study, we investigated anchor residues in intrinsically disordered proteins (IDPs which are flexible in the free state. We identified the anchor residues of the N-terminus of the p53 protein (Glu17–Asn29, abbreviated as p53N which are involved in binding with two different targets (MDM2 and Taz2, and analyzed their side chain conformations in the unbound states. The anchor residues in the unbound p53N were found to frequently sample conformations similar to those observed in the bound complexes (i.e., Phe19, Trp23, and Leu26 in the p53N-MDM2 complex, and Leu22 in the p53N-Taz2 complex. We argue that the bound-like conformations of the anchor residues in the unbound state are important for controlling the specific interactions between IDPs and their targets. Further, we propose a mechanism to account for the binding promiscuity of IDPs in terms of anchor residues and molecular recognition features (MoRFs.

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

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    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.

  17. Targeting GRP75 improves HSP90 inhibitor efficacy by enhancing p53-mediated apoptosis in hepatocellular carcinoma. (United States)

    Guo, Weiwei; Yan, Lichong; Yang, Ling; Liu, Xiaoyu; E, Qiukai; Gao, Peiye; Ye, Xiaofei; Liu, Wen; Zuo, Ji


    Heat shock protein 90 (HSP90) inhibitors are potential drugs for cancer therapy. The inhibition of HSP90 on cancer cell growth largely through degrading client proteins, like Akt and p53, therefore, triggering cancer cell apoptosis. Here, we show that the HSP90 inhibitor 17-AAG can induce the expression of GRP75, a member of heat shock protein 70 (HSP70) family, which, in turn, attenuates the anti-growth effect of HSP90 inhibition on cancer cells. Additionally, 17-AAG enhanced binding of GRP75 and p53, resulting in the retention of p53 in the cytoplasm. Blocking GRP75 with its inhibitor MKT-077 potentiated the anti-tumor effects of 17-AAG by disrupting the formation of GRP75-p53 complexes, thereby facilitating translocation of p53 into the nuclei and leading to the induction of apoptosis-related genes. Finally, dual inhibition of HSP90 and GRP75 was found to significantly inhibit tumor growth in a liver cancer xenograft model. In conclusion, the GRP75 inhibitor MKT-077 enhances 17-AAG-induced apoptosis in HCCs and increases p53-mediated inhibition of tumor growth in vivo. Dual targeting of GRP75 and HSP90 may be a useful strategy for the treatment of HCCs.

  18. Targeting GRP75 improves HSP90 inhibitor efficacy by enhancing p53-mediated apoptosis in hepatocellular carcinoma.

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    Weiwei Guo

    Full Text Available Heat shock protein 90 (HSP90 inhibitors are potential drugs for cancer therapy. The inhibition of HSP90 on cancer cell growth largely through degrading client proteins, like Akt and p53, therefore, triggering cancer cell apoptosis. Here, we show that the HSP90 inhibitor 17-AAG can induce the expression of GRP75, a member of heat shock protein 70 (HSP70 family, which, in turn, attenuates the anti-growth effect of HSP90 inhibition on cancer cells. Additionally, 17-AAG enhanced binding of GRP75 and p53, resulting in the retention of p53 in the cytoplasm. Blocking GRP75 with its inhibitor MKT-077 potentiated the anti-tumor effects of 17-AAG by disrupting the formation of GRP75-p53 complexes, thereby facilitating translocation of p53 into the nuclei and leading to the induction of apoptosis-related genes. Finally, dual inhibition of HSP90 and GRP75 was found to significantly inhibit tumor growth in a liver cancer xenograft model. In conclusion, the GRP75 inhibitor MKT-077 enhances 17-AAG-induced apoptosis in HCCs and increases p53-mediated inhibition of tumor growth in vivo. Dual targeting of GRP75 and HSP90 may be a useful strategy for the treatment of HCCs.

  19. Genomic profiling of murine mammary tumors identifies potential personalized drug targets for p53-deficient mammary cancers

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    Adam D. Pfefferle


    Full Text Available Targeted therapies against basal-like breast tumors, which are typically ‘triple-negative breast cancers (TNBCs’, remain an important unmet clinical need. Somatic TP53 mutations are the most common genetic event in basal-like breast tumors and TNBC. To identify additional drivers and possible drug targets of this subtype, a comparative study between human and murine tumors was performed by utilizing a murine Trp53-null mammary transplant tumor model. We show that two subsets of murine Trp53-null mammary transplant tumors resemble aspects of the human basal-like subtype. DNA-microarray, whole-genome and exome-based sequencing approaches were used to interrogate the secondary genetic aberrations of these tumors, which were then compared to human basal-like tumors to identify conserved somatic genetic features. DNA copy-number variation produced the largest number of conserved candidate personalized drug targets. These candidates were filtered using a DNA-RNA Pearson correlation cut-off and a requirement that the gene was deemed essential in at least 5% of human breast cancer cell lines from an RNA-mediated interference screen database. Five potential personalized drug target genes, which were spontaneously amplified loci in both murine and human basal-like tumors, were identified: Cul4a, Lamp1, Met, Pnpla6 and Tubgcp3. As a proof of concept, inhibition of Met using crizotinib caused Met-amplified murine tumors to initially undergo complete regression. This study identifies Met as a promising drug target in a subset of murine Trp53-null tumors, thus identifying a potential shared driver with a subset of human basal-like breast cancers. Our results also highlight the importance of comparative genomic studies for discovering personalized drug targets and for providing a preclinical model for further investigations of key tumor signaling pathways.

  20. Pharmacological targeting of p53 through RITA is an effective antitumoral strategy for malignant pleural mesothelioma. (United States)

    Di Marzo, Domenico; Forte, Iris Maria; Indovina, Paola; Di Gennaro, Elena; Rizzo, Valeria; Giorgi, Francesca; Mattioli, Eliseo; Iannuzzi, Carmelina Antonella; Budillon, Alfredo; Giordano, Antonio; Pentimalli, Francesca


    Malignant mesothelioma, a very aggressive tumor associated to asbestos exposure, is expected to increase in incidence, and unfortunately, no curative modality exists. Reactivation of p53 is a new attractive antitumoral strategy. p53 is rarely mutated in mesothelioma, but it is inactivated in most tumors by the lack of p14(ARF). Here, we evaluated the feasibility of this approach in pleural mesothelioma by testing RITA and nutlin-3, two molecules able to restore p53 function through a different mechanism, on a panel of mesothelioma cell lines representing the epithelioid (NCI-H28, NCI-H2452, IST-MES 2), biphasic (MSTO-211H), and sarcomatoid (NCI-H2052) histotypes compared with the normal mesothelial HMC-hTERT. RITA triggered robust caspase-dependent apoptosis specifically in epithelioid and biphasic mesothelioma cell lines, both through wild-type and mutant p53, concomitant to p21 downregulation. Conversely, nutlin-3 induced a p21-dependent growth arrest, rather than apoptosis, and was slightly toxic on HMC-hTERT.   Interestingly, we identified a previously undetected point mutation of p53 (p.Arg249Ser) in IST-MES 2, and showed that RITA is also able to reactivate this p53 mutant protein and its apoptotic function. RITA reduced tumor growth in a MSTO-211H-derived xenograft model of mesothelioma and synergized with cisplatin, which is the mainstay of treatment for this tumor. Our data indicate that reactivation of p53 and concomitant p21 downregulation effectively induce cell death in mesothelioma, a tumor characterized by a high intrinsic resistance to apoptosis. Altogether, our findings provide the preclinical framework supporting the use of p53-reactivating agents alone, or in combination regimens, to improve the outcome of patients with mesothelioma.

  1. The Double Role of p53 in Cancer and Autoimmunity and Its Potential as Therapeutic Target. (United States)

    Fierabracci, Alessandra; Pellegrino, Marsha


    p53 is a sequence-specific short-lived transcription factor expressed at low concentrations in various tissues while it is upregulated in damaged, tumoral or inflamed tissue. In normally proliferating cells, p53 protein levels and function are tightly controlled by main regulators, i.e., MDM2 (mouse double minute 2) and MDM4 proteins. p53 plays an important role due to its ability to mediate tumor suppression. In addition to its importance as a tumor suppressor, p53 coordinates diverse cellular responses to stress and damage and plays an emerging role in various physiological processes, including fertility, cell metabolism, mitochondrial respiration, autophagy, cell adhesion, stem cell maintenance and development. Interestingly, it has been recently implicated in the suppression of autoimmune and inflammatory diseases in both mice and humans. In this review based on current knowledge on the functional properties of p53 and its regulatory pathways, we discuss the potential utility of p53 reactivation from a therapeutic perspective in oncology and chronic inflammatory disorders leading to autoimmunity.

  2. Integration of Genomic, Biologic, and Chemical Approaches to Target p53 Loss and Gain-of-Function in Triple Negative Breast Cancer (United States)


    Approaches to Target p53 Loss and Gain-of-Function in Triple Negative Breast Cancer PRINCIPAL INVESTIGATOR: Jennifer A. Pietenpol, Ph.D...Biologic, and Chemical Approaches to Target p53 Loss and Gain-of-Function in Triple Negative Breast Cancer 5a. CONTRACT NUMBER...states resulting from alterations in the p53 signaling pathway in triple negative breast cancer (TNBC). Development of therapies for TNBC is a

  3. P53 in human melanoma fails to regulate target genes associated with apoptosis and the cell cycle and may contribute to proliferation

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    Rizos Helen


    Full Text Available Abstract Background Metastatic melanoma represents a major clinical problem. Its incidence continues to rise in western countries and there are currently no curative treatments. While mutation of the P53 tumour suppressor gene is a common feature of many types of cancer, mutational inactivation of P53 in melanoma is uncommon; however, its function often appears abnormal. Methods In this study whole genome bead arrays were used to examine the transcript expression of P53 target genes in extracts from 82 melanoma metastases and 6 melanoma cell lines, to provide a global assessment of aberrant P53 function. The expression of these genes was also examined in extracts derived from diploid human melanocytes and fibroblasts. Results The results indicated that P53 target transcripts involved in apoptosis were under-expressed in melanoma metastases and melanoma cell lines, while those involved in the cell cycle were over-expressed in melanoma cell lines. There was little difference in the transcript expression of P53 target genes between cell lines with null/mutant P53 compared to those with wild-type P53, suggesting that altered expression in melanoma was not related to P53 status. Similarly, down-regulation of P53 by short-hairpin RNA (shRNA had limited effect on P53 target gene expression in melanoma cells, whereas there were a large number of P53 target genes whose mRNA expression was significantly altered by P53 inhibition in melanocytes. Analysis of whole genome gene expression profiles indicated that the ability of P53 to regulate genes involved in the cell cycle was significantly reduced in melanoma cells. Moreover, inhibition of P53 in melanocytes induced changes in gene expression profiles that were characteristic of melanoma cells and resulted in increased proliferation. Conversely, knockdown of P53 in melanoma cells resulted in decreased proliferation. Conclusions These results indicate that P53 target genes involved in apoptosis and cell

  4. Anomalous altered expressions of downstream gene-targets in TP53-miRNA pathways in head and neck cancer. (United States)

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


    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.

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

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    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.

  6. Rotenone affects p53 transcriptional activity and apoptosis via targeting SIRT1 and H3K9 acetylation in SH-SY5Y cells. (United States)

    Feng, Ya; Liu, Te; Dong, Su-Yan; Guo, Yan-Jie; Jankovic, Joseph; Xu, Huaxi; Wu, Yun-Cheng


    The protein deacetylase SIRT1 has been recognized to exert its protective effect by directly deacetylasing histone and many other transcriptional factors including p53. However, the effect of SIRT1 on p53 expression at the transcriptional level still remains to be elucidated. In this study, we found that rotenone treatment decreased cell viability, induced apoptosis, reduced SIRT1 level, and promoted p53 expression. Pre-treatment with resveratrol, a SIRT1 activator, could attenuate rotenone-induced cell injury and p53 expression, whereas down-regulation of SIRT1 directly increased p53 expression. Moreover, chromatin immunoprecipitation experiments showed that SIRT1 bound to H3K9 within the p53 promoter region, and this binding resulted in decreased H3K9 acetylation and increased H3K9 tri-methylation, thereby inhibiting p53 gene transcription. In conclusion, our data indicate that rotenone promotes p53 transcription and apoptosis through targeting SIRT1 and H3K9. This leads to nigrostriatal degeneration, the main pathogenic mechanism of motor features of Parkinson's disease. SIRT1, a deacetylase enzyme, has neuroprotective effects for Parkinson's disease via targeting various factors. Resveratrol activated SIRT1 can target H3K9 and regulate p53 gene expression at the transcriptional level, thus inhibiting p53 transcription to enhance neuroprotection, alleviating rotenone induced dopaminergic neurodegeneration. We think these findings should provide a new strategy for the treatment of Parkinson's disease.

  7. 11R-P53 and GM-CSF Expressing Oncolytic Adenovirus Target Cancer Stem Cells with Enhanced Synergistic Activity (United States)

    Lv, Sai-qun; Ye, Zhen-long; Liu, Pin-yi; Huang, Yao; Li, Lin-fang; Liu, Hui; Zhu, Hai-li; Jin, Hua-jun; Qian, Qi-jun


    Targeting cancer stem cells with oncolytic virus (OV) holds great potential for thorough elimination of cancer cells. Based on our previous studies, we here established 11R-P53 and mGM-CSF carrying oncolytic adenovirus (OAV) SG655-mGMP and investigated its therapeutic effect on hepatocellular carcinoma stem cells Hep3B-C and teratoma stem cells ECCG5. Firstly, the augmenting effect of 11R in our construct was tested and confirmed by examining the expression of EGFP with Fluorescence and FCM assays after transfecting Hep3B-C and ECCG5 cells with OVA SG7605-EGFP and SG7605-11R-EGFP. Secondly, the expressions of 11R-P53 and GM-CSF in Hep3B-C and ECCG5 cells after transfection with OAV SG655-mGMP were detected by Western blot and Elisa assays, respectively. Thirdly, the enhanced growth inhibitory and augmented apoptosis inducing effects of OAV SG655-mGMP on Hep3B-C and ECCG5 cells were tested with FCM assays by comparing with the control, wild type 5 adenovirus, 11R-P53 carrying OVA in vitro. Lastly, the in vivo therapeutic effect of OAV SG655-mGMP toward ECCG5 cell-formed xenografts was studied by measuring tumor volumes post different treatments with PBS, OAV SG655-11R-P53, OAV SG655-mGM-CSF and OAV SG655-mGMP. Treatment with OAV SG655-mGMP induced significant xenograft growth inhibition, inflammation factor AIF1 expression and immune cells infiltration. Therefore, our OAV SG655-mGMP provides a novel platform to arm OVs to target cancer stem cells.

  8. Safety and Efficacy in Advanced Solid Tumors of a Targeted Nanocomplex Carrying the p53 Gene Used in Combination with Docetaxel: A Phase 1b Study. (United States)

    Pirollo, Kathleen F; Nemunaitis, John; Leung, Po Ki; Nunan, Robert; Adams, Jana; Chang, Esther H


    Loss of p53 suppressor function, through mutations or inactivation of the p53 pathway, occurs in most human cancers. SGT-53 is a liposomal nanocomplex designed for systemic, tumor-targeting delivery of the wt p53 gene. In this nanodelivery system, an anti-transferrin receptor single-chain antibody fragment serves as the targeting moiety. In an initial phase 1 trial in patients with advanced solid tumors, SGT-53 demonstrated tumor-specific targeting, was shown to be well tolerated, and was associated with an antitumor effect in several patients. Our preclinical studies have also demonstrated enhanced antitumor activity with the combination of SGT-53 and docetaxel. Thus, this dose-escalation trial was undertaken to assess the combination of SGT-53 and docetaxel for safety and potential efficacy in 14 advanced cancer patients. Results reveal that the combination of SGT-53 (maximum dose, 3.6 mg DNA/infusion) and docetaxel (75 mg/m(2)/infusion) was well tolerated. Moreover, clinical activity involving 12 evaluable patients was observed. Three of these patients achieved RECIST-verified partial responses with tumor reductions of -47%, -51%, and -79%. Two others had stable disease with significant shrinkage (-25% and -16%). These results support phase 2 testing of SGT-53 in combination with docetaxel.

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

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    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.

  10. The Wnt Target Protein Peter Pan Defines a Novel p53-independent Nucleolar Stress-Response Pathway. (United States)

    Pfister, Astrid S; Keil, Marina; Kühl, Michael


    Proper ribosome formation is a prerequisite for cell growth and proliferation. Failure of this process results in nucleolar stress and p53-mediated apoptosis. The Wnt target Peter Pan (PPAN) is required for 45 S rRNA maturation. So far, the role of PPAN in nucleolar stress response has remained elusive. We demonstrate that PPAN localizes to mitochondria in addition to its nucleolar localization and inhibits the mitochondrial apoptosis pathway in a p53-independent manner. Loss of PPAN induces BAX stabilization, depolarization of mitochondria, and release of cytochrome c, demonstrating its important role as an anti-apoptotic factor. Staurosporine-induced nucleolar stress and apoptosis disrupt nucleolar PPAN localization and induce its accumulation in the cytoplasm. This is accompanied by phosphorylation and subsequent cleavage of PPAN by caspases. Moreover, we show that PPAN is a novel interaction partner of the anti-apoptotic protein nucleophosmin (NPM). PPAN depletion induces NPM and upstream-binding factor (UBF) degradation, which is independent of caspases. In summary, we provide evidence for a novel nucleolar stress-response pathway involving PPAN, NPM, and BAX to guarantee cell survival in a p53-independent manner.


    Energy Technology Data Exchange (ETDEWEB)



    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

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


    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.

  13. Forkhead transcription factor FOXF1 is a novel target gene of the p53 family and regulates cancer cell migration and invasiveness. (United States)

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


    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.

  14. p53 activated by AND gate genetic circuit under radiation and hypoxia for targeted cancer gene therapy. (United States)

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


    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.

  15. Dendritic cells pulsed with alpha-fetoprotein and mutant P53 fused gene induce bi-targeted cytotoxic T lymphocyte response against hepatic carcinoma. (United States)

    Ren, Jun; Jia, Jun; Zhang, Hongmei; Zhang, Liwang; Ma, Bo; Jiang, Hanfang; Di, Lijun; Song, Guohong; Yu, Jing


    Dendritic cell (DC)-based immunotherapy is rapidly emerging as a promising treatment in cancer therapy. We had previously shown that DC pulsed with either defined mRNA of tumor antigen (Ag) such as alpha-fetoprotein (AFP), or total RNA of hepatocellular carcinoma (HCC) could elicit Ag-specific cytotoxic T lymphocyte (CTL) response. Therefore, we suggested a novel DC-based therapeutic method, in which DCs derived from CD34(+) cells enriched peripheral blood mononuclear cells were pulsed with liposome-coated AFP and mutant P53 (mtP53) fused gene pEGFP-C3/AFP-mtP53 to induce bi-targeted specific CTL responses against HCC. Three different genotype HCC cell lines, HepG2 (human histocompatibility leukocyte antigens (HLA) A2 positive, AFP expressing positive, P53 expressing negative), SMMC7721 (HLA A2 positive, neither AFP nor P53 expressing positive), and HMCC97 (HLA A2 positive, both AFP and P53 expressing positive) were selected as targets for CTL responses. An important finding was that DCs pulsed with the liposome-coated fused gene could evoke more intensive bi-targeted Ag-specific CTL responses against HMCC97 than DCs pulsed with either AFP or P53 single gene (P gene of different Ags might induce more extensive multitargeted antitumor immunity.

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

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


    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

  17. 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


    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.

  18. 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


    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

  19. WRAP53 Is Essential for Cajal Body Formation and for Targeting the Survival of Motor Neuron Complex to Cajal Bodies


    Salah Mahmoudi; Sofia Henriksson; Irene Weibrecht; Stephen Smith; Ola Söderberg; Staffan Strömblad; Klas G Wiman; Marianne Farnebo


    The WRAP53 gene gives rise to a p53 antisense transcript that regulates p53. This gene also encodes a protein that directs small Cajal body-specific RNAs to Cajal bodies. Cajal bodies are nuclear organelles involved in diverse functions such as processing ribonucleoproteins important for splicing. Here we identify the WRAP53 protein as an essential factor for Cajal body maintenance and for directing the survival of motor neuron (SMN) complex to Cajal bodies. By RNA interference and immunofluo...

  20. PBK/TOPK interacts with the DBD domain of tumor suppressor p53 and modulates expression of transcriptional targets including p21. (United States)

    Hu, F; Gartenhaus, R B; Eichberg, D; Liu, Z; Fang, H-B; Rapoport, A P


    PBK/TOPK (PDZ-binding kinase, T-LAK-cell-originated protein kinase) is a serine-threonine kinase that is overexpressed in a variety of tumor cells but its role in oncogenesis remains unclear. Here we show, by co-immunoprecipitation experiments and yeast two-hybrid analysis, that PBK/TOPK physically interacts with the tumor suppressor p53 through its DNA-binding (DBD) domain in HCT116 colorectal carcinoma cells that express wild-type p53. PBK also binds to p53 mutants carrying five common point mutations in the DBD domain. The PBK-p53 interaction appears to downmodulate p53 transactivation function as indicated by PBK/TOPK knockdown experiments, which show upregulated expression of the key p53 target gene and cyclin-dependent kinase inhibitor p21 in HCT116 cells, particularly after genotoxic damage from doxorubicin. Furthermore, stable PBK/TOPK knockdown cell lines (derived from HCT116 and MCF-7 cells) showed increased apoptosis, G(2)/M arrest and slower growth as compared to stable empty vector-transfected control cell lines. Gene microarray studies identified additional p53 target genes involved in apoptosis or cell cycling, which were differentially regulated by PBK knockdown. Together, these data suggest that increased levels of PBK/TOPK may contribute to tumor cell development and progression through suppression of p53 function and consequent reductions in the cell-cycle regulatory proteins such as p21. PBK/TOPK may therefore be a valid target for antineoplastic kinase inhibitors to sensitize tumor cells to chemotherapy-induced apoptosis and growth suppression.

  1. Chromium in diet (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 ...

  2. 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.

  3. 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


    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...

  4. Heterogeneous chromium catalysts

    NARCIS (Netherlands)


    The present invention relates to a heterogeneous chromium catalyst system for the polymerisation of ethylene and/or alpha olefins prepared by the steps of: (a) providing a silica-containing support, (b) treating the silica-containing support with a chromium compound to form a chromium-based silica-c

  5. P53 gene could be a new effective therapeutic target in triple-negative breast cancer:a Meta-analysis*

    Institute of Scientific and Technical Information of China (English)

    Fang Guo; Zhaozhe Liu(Co-first author); Hongbo Liu; Xiaodong Xie


    Objective:The aim of this study was to explore the relationship between p53 gene and triple-negative breast cancer (TNBC), and determine that whether p53 gene could be a new ef ective therapeutic target. Methods:We identified studies with quantitative data on the relation of p53 gene and TNBC through searching 12 databases online (Oct. 1999-Oct. 2012) and reviewing the references, which were written in English or Chinese. Summary estimates of odds ratio (OR) was calculated using the fixed-ef ects model or the random-ef ects model as appropriate. Results:We identified 12 eligible stud-ies with 1532 cases of TNBC patients and 6329 controls of non-TNBC patients. The test for homogeneity resulted inχ2=200.16 (P<0.05), it showed significant heterogeneity so that a random ef ect model was applied. Our results showed that the expression of p53 gene could be much stronger in TNBC group than that in non-TNBC group [OR=2.10, 95%confidence interval (CI)=1.21-3.65]. In ethnicity-subgroup analysis, we found that in Caucasian group, the expression of p53 gene were stronger in TNBC group (OR=2.60, 95%CI=1.21-5.57), but there was no statistical significance in Asian group (OR=1.69, 95%CI=0.83-3.45). Conclusion:P53 gene could be an ef ective predictor and a good therapeutic target for TNBC patients in the future, especial y in Caucasian. Further researches focusing on p53 gene would gain a breakthrough in the treatment of TNBC.

  6. Targeted sequencing reveals TP53 as a potential diagnostic biomarker in the post-treatment surveillance of head and neck cancer. (United States)

    van Ginkel, Joost H; de Leng, Wendy W J; de Bree, Remco; van Es, Robert J J; Willems, Stefan M


    Head and neck squamous cell carcinomas (HNSCC) form a large heterogeneous group of tumors and have a relatively poor outcome in advanced cases. Revealing the underlying genetic mutations in HNSCC facilitates the development of diagnostic biomarkers, which might lead to improved diagnosis and post treatment surveillance. We retrospectively analyzed mutational hotspots using targeted next-generation sequencing (NGS) of 239 HNSCC tumor samples in order to examine the mutational profile of HNSCC. Furthermore, we assessed prevalence, co-occurrence, and synonymy of gene mutations in (matched) tumor samples. TP53 was found mutated the most frequent with mutation rates of up to 83% in all tumors, compared to mutation rates of between 0 and 21% of CDKN2A, PIK3CA, HRAS, CDK4, FBXW7 and RB1. Mutational co-occurrence predominantly existed between TP53 and PIK3CA, TP53 and CDKN2A, and HRAS and PIK3CA. Mutational synonymy between primary tumor and associated metastasis and recurrence was present in respectively 88% and 89%. TP53 mutations were concordantly mutated in 95% of metastases and in 91% of recurrences. This indicates TP53 mutations to be highly prevalent and concordant in primary tumors and associated locoregional metastases and recurrences. In turn, this provides ground for further investigating the use of TP53 mutations as diagnostic biomarkers in HNSCC patients.

  7. The pharmacodynamics of the p53-Mdm2 targeting drug Nutlin: the role of gene-switching noise.

    Directory of Open Access Journals (Sweden)

    Krzysztof Puszynski


    Full Text Available In this work we investigate, by means of a computational stochastic model, how tumor cells with wild-type p53 gene respond to the drug Nutlin, an agent that interferes with the Mdm2-mediated p53 regulation. In particular, we show how the stochastic gene-switching controlled by p53 can explain experimental dose-response curves, i.e., the observed inter-cell variability of the cell viability under Nutlin action. The proposed model describes in some detail the regulation network of p53, including the negative feedback loop mediated by Mdm2 and the positive loop mediated by PTEN, as well as the reversible inhibition of Mdm2 caused by Nutlin binding. The fate of the individual cell is assumed to be decided by the rising of nuclear-phosphorylated p53 over a certain threshold. We also performed in silico experiments to evaluate the dose-response curve after a single drug dose delivered in mice, or after its fractionated administration. Our results suggest that dose-splitting may be ineffective at low doses and effective at high doses. This complex behavior can be due to the interplay among the existence of a threshold on the p53 level for its cell activity, the nonlinearity of the relationship between the bolus dose and the peak of active p53, and the relatively fast elimination of the drug.

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

    DEFF Research Database (Denmark)

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


    MicroRNAs (miRNAs) regulate many key cancer-relevant pathways and may themselves possess oncogenic or tumor-suppressor functions. Consequently, miRNA dysregulation has been shown to be a prominent feature in many human cancers. The p53 tumor suppressor acts as a negative regulator of cell...... 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...... 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...

  9. Mir-660 is downregulated in lung cancer patients and its replacement inhibits lung tumorigenesis by targeting MDM2-p53 interaction. (United States)

    Fortunato, O; Boeri, M; Moro, M; Verri, C; Mensah, M; Conte, D; Caleca, L; Roz, L; Pastorino, U; Sozzi, G


    Lung cancer represents the leading cause of cancer-related death in developed countries. Despite the advances in diagnostic and therapeutic techniques, the 5-year survival rate remains low. The research for novel therapies directed to biological targets has modified the therapeutic approach, but the frequent engagement of resistance mechanisms and the substantial costs, limit the ability to reduce lung cancer mortality. MicroRNAs (miRNAs) are small noncoding RNAs with known regulatory functions in cancer initiation and progression. In this study we found that mir-660 expression is downregulated in lung tumors compared with adjacent normal tissues and in plasma samples of lung cancer patients with poor prognosis, suggesting a potential functional role of this miRNA in lung tumorigenesis. Transient and stable overexpression of mir-660 using miRNA mimics reduced migration, invasion, and proliferation properties and increased apoptosis in p53 wild-type lung cancer cells (NCI-H460, LT73, and A549). Furthermore, stable overexpression using lentiviral vectors in NCI-H460 and A549 cells inhibited tumor xenograft growth in immunodeficient mice (95 and 50% reduction compared with control, respectively), whereas the effects of mir-660 overexpression were absent in H1299, a lung cancer cell line lacking p53 locus, both in in vitro and in vivo assays. We identified and validated mouse double minute 2 (MDM2) gene, a key regulator of the expression and function of p53, as a new direct target of mir-660. In addition, mir-660 expression reduced both mRNA and protein expression of MDM2 in all cell lines and stabilized p53 protein levels resulting in an upregulation of p21(WAF1/CIP1) in p53 wild-type cells. Our finding supports that mir-660 acts as a tumor suppressor miRNA and we suggest the replacement of mir-660 as a new therapeutic approach for p53 wild-type lung cancer treatment.

  10. Maximal killing of lymphoma cells by DNA damage-inducing therapy requires not only the p53 targets Puma and Noxa, but also Bim. (United States)

    Happo, Lina; Cragg, Mark S; Phipson, Belinda; Haga, Jon M; Jansen, Elisa S; Herold, Marco J; Dewson, Grant; Michalak, Ewa M; Vandenberg, Cassandra J; Smyth, Gordon K; Strasser, Andreas; Cory, Suzanne; Scott, Clare L


    DNA-damaging chemotherapy is the backbone of cancer treatment, although it is not clear how such treatments kill tumor cells. In nontransformed lymphoid cells, the combined loss of 2 proapoptotic p53 target genes, Puma and Noxa, induces as much resistance to DNA damage as loss of p53 itself. In Eμ-Myc lymphomas, however, lack of both Puma and Noxa resulted in no greater drug resistance than lack of Puma alone. A third B-cell lymphoma-2 homology domain (BH)3-only gene, Bim, although not a direct p53 target, was up-regulated in Eμ-Myc lymphomas incurring DNA damage, and knockdown of Bim levels markedly increased the drug resistance of Eμ-Myc/Puma(-/-)Noxa(-/-) lymphomas both in vitro and in vivo. Remarkably, c-MYC-driven lymphoma cell lines from Noxa(-/-)Puma(-/-)Bim(-/-) mice were as resistant as those lacking p53. Thus, the combinatorial action of Puma, Noxa, and Bim is critical for optimal apoptotic responses of lymphoma cells to 2 commonly used DNA-damaging chemotherapeutic agents, identifying Bim as an additional biomarker for treatment outcome in the clinic.

  11. miR-125b targets DNMT3b and mediates p53 DNA methylation involving in the vascular smooth muscle cells proliferation induced by homocysteine. (United States)

    Cao, ChengJian; Zhang, HuiPing; Zhao, Li; Zhou, Longxia; Zhang, Minghao; Xu, Hua; Han, Xuebo; Li, Guizhong; Yang, Xiaoling; Jiang, YiDeng


    MicroRNAs (miRNAs) are short non-coding RNA and play crucial roles in a wide array of biological processes, including cell proliferation, differentiation and apoptosis. Our previous studies found that homocysteine(Hcy) can stimulate the proliferation of vascular smooth muscle cells (VSMCs), however, the underlying mechanisms were not fully elucidated. Here, we found proliferation of VSMCs induced by Hcy was of correspondence to the miR-125b expression reduced both in vitro and in the ApoE knockout mice, the hypermethylation of p53, its decreased expression, and DNA (cytosine-5)-methyltransferase 3b (DNMT3b) up-regulated. And, we found DNMT3b is a target of miR-125b, which was verified by the Dual-Luciferase reporter assay and western blotting. Besides, the siRNA interference for DNMT3b significantly decreased the methylation level of p53, which unveiled the causative role of DNMT3b in p53 hypermethylation. miR-125b transfection further confirmed its regulative roles on p53 gene methylation status and the VSMCs proliferation. Our data suggested that a miR-125b-DNMT3b-p53 signal pathway may exist in the VSMCs proliferation induced by Hcy.

  12. MicroRNA-128-2 targets the transcriptional repressor E2F5 enhancing mutant p53 gain of function (United States)

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


    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

  13. 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


    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

  14. Targeted next-generation sequencing of cancer genes identified frequent TP53 and ATRX mutations in leiomyosarcoma. (United States)

    Yang, Ching-Yao; Liau, Jau-Yu; Huang, Wei-Ju; Chang, Yu-Ting; Chang, Ming-Chu; Lee, Jen-Chieh; Tsai, Jia-Huei; Su, Yi-Ning; Hung, Chia-Cheng; Jeng, Yung-Ming


    Leiomyosarcoma is an aggressive soft tissue sarcoma with poor patient survival. The genetic changes of leiomyosarcoma remain to be discovered. In this study, we analyzed the genetic changes of 44 cancer-related genes by using next-generation sequencing in 54 leiomyosarcomas. We identified TP53 mutations in 19 of the 54 tumors (35%) and ATRX mutations in 9 of the 54 tumors (17%). The TP53-mutated leiomyosarcomas were limited to female patients (P = 0.006). All but 2 of the TP53-mutated leiomyosarcomas were located in the uterus (n = 11) or retroperitoneum (n = 6). The ATRX mutations were associated with poorly differentiated leiomyosarcomas (P = 0.028) and the presence of tumor necrosis (P = 0.015). Kaplan-Meier survival analysis showed that patients with ATRX-mutated leiomyosarcomas had worse overall survival than did patients with ATRX-wild-type leiomyosarcomas. All of the ATRX-mutated leiomyosarcomas showed the alternative lengthening of telomere phenotype. The ATRX mutations did not correlate with ATRX protein expression, as detected using immunohistochemistry. In conclusion, we identified loss of function of the p53 and ATRX pathways being the main mechanisms for leiomyosarcomas. The molecular mechanisms may provide new opportunities to treat these aggressive neoplasms.

  15. Stapled peptides in the p53 pathway: computer simulations reveal novel interactions of the staples with the target protein. (United States)

    Joseph, Thomas Leonard; Lane, David; Verma, Chandra S


    Atomistic simulations of a set of stapled peptides derived from the transactivation domain of p53 (designed by Verdine & colleagues, JACS 2007 129:2456) and complexed to MDM2 reveal that the good binders are uniquely characterized by higher helicity and by extensive interactions between the hydrocarbon staples and the MDM2 surface; in contrast the poor binders have reduced helicity and their staples are mostly solvent exposed. Our studies also find that the best binders can also potentially inhibit MDMX with similar affinities, suggesting that such stapled peptides can be evolved for dual inhibition with therapeutic potential.

  16. 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


    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.

  17. Metabonomics applied in exploring the antitumour mechanism of physapubenolide on hepatocellular carcinoma cells by targeting glycolysis through the Akt-p53 pathway (United States)

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


    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

  18. 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


    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.

  19. Synthesis, characterization, and in vitro evaluation of targeted gold nanoshelled poly(d,l-lactide-co-glycolide) nanoparticles carrying anti p53 antibody as a theranostic agent for ultrasound contrast imaging and photothermal therapy. (United States)

    Xu, Li; Wan, Caifeng; Du, Jing; Li, Hongli; Liu, Xuesong; Yang, Hong; Li, Fenghua


    Breast cancer is the leading cause of cancer-related deaths in women and earlier detection can substantially reduce deaths from breast cancer. Polymers with targeted ligands are widely used in the field of molecular ultrasound imaging and targeted tumor therapy. In our study, the nanotheranostic agent was fabricated through filling perfluoropropane (C3F8) into poly(d,l-lactic-co-glycolic acid) nanoparticles (PLGA NPs), followed by the formation of gold nanoshell on the surface, then conjugated with anti p53 antibody which has high specificity with the p53 protein overexpressing in breast cancer. The average diameter of the gold nanoshelled PLGA NPs carrying anti p53 antibody (p53-PLGA@Au NPs) was 247 ± 108.2 nm. The p53-PLGA@Au NPs had well-defined spherical morphology and hollow interiors observed by electron microscope, and had a good photothermal effect under the irradiation of an 808 nm laser. The results of laser scanning confocal microscope (LSCM) and flow cytometer (FCM) indicated the specific targeting of p53-PLGA@Au NPs conjugating with breast cancer MCF-7 cells overexpressing p53 protein in vitro. Also the ultrasound imaging experiments in vitro showed that p53-PLGA@Au NPs were suitable for ultrasound contrast imaging. In conclusion, the p53-PLGA@Au NPs are demonstrated to be novel targeted UCAs and may have potential applications in the early diagnosis and targeted near-infrared (NIR) photothermal therapy of breast cancer in the future.

  20. p53转录非依赖活性介导细胞凋亡%p53:pro-death factor that directly targets mitochondria for triggering apoptosis

    Institute of Scientific and Technical Information of China (English)

    钱呈睿; 葛海良; 王颖



  1. 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


    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

  2. MicroRNA-34a affects chondrocyte apoptosis and proliferation by targeting the SIRT1/p53 signaling pathway during the pathogenesis of osteoarthritis. (United States)

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


    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.

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


    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.

  4. A genome-wide siRNA screen for regulators of tumor suppressor p53 activity in human non-small lung cancer cells identifies components of the RNA splicing machinery as targets for anticancer treatment. (United States)

    Siebring-van Olst, Ellen; Blijlevens, Maxime; de Menezes, Renee X; van der Meulen-Muileman, Ida H; Smit, Egbert F; van Beusechem, Victor W


    Reinstating wild-type tumor suppressor p53 activity could be a valuable option for the treatment of cancer. To contribute to development of new treatment options for non-small cell lung cancer (NSCLC), we performed genome-wide siRNA screens for determinants of p53 activity in NSCLC cells. We identified many genes not previously known to be involved in regulating p53 activity. Silencing p53 pathway inhibitor genes was associated with loss of cell viability. The largest functional gene cluster influencing p53 activity was mRNA splicing. Prominent p53 activation was observed upon silencing of specific spliceosome components, rather than by general inhibition of the spliceosome. Ten genes were validated as inhibitors of p53 activity in multiple NSCLC cell lines: genes encoding the Ras-pathway activator SOS1, the zinc finger protein TSHZ3, the mitochondrial membrane protein COX16 and the spliceosome components SNRPD3, SF3A3, SF3B1, SF3B6, XAB2, CWC22 and HNRNPL. Silencing these genes generally increased p53 levels, with distinct effects on CDKN1A expression, induction of cell cycle arrest and cell death. Silencing spliceosome components was associated with alternative splicing of MDM4 mRNA, which could contribute to activation of p53. In addition, silencing splice factors was particularly effective in killing NSCLC cells, albeit in a p53-independent manner. Interestingly, silencing SNRPD3 and SF3A3 exerted much stronger cytotoxicity to NSCLC cells than to lung fibroblasts, suggesting that these genes could represent useful therapeutic targets. This article is protected by copyright. All rights reserved.

  5. 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


    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

  6. 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:; 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)


    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

  7. The p53 pathway in breast cancer


    Gasco, Milena; Shami, Shukri; Crook, Tim


    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...

  8. Measuring cytotoxicity by bioluminescence imaging outperforms the standard chromium-51 release assay.

    Directory of Open Access Journals (Sweden)

    Mobin A Karimi

    Full Text Available The chromium-release assay developed in 1968 is still the most commonly used method to measure cytotoxicity by T cells and by natural killer cells. Target cells are loaded in vitro with radioactive chromium and lysis is determined by measuring chromium in the supernatant released by dying cells. Since then, alternative methods have been developed using different markers of target cell viability that do not involve radioactivity. Here, we compared and contrasted a bioluminescence (BLI-based cytotoxicity assay to the standard radioactive chromium-release assay using an identical set of effector cells and tumor target cells. For this, we stably transduced several human and murine tumor cell lines to express luciferase. When co-cultured with cytotoxic effector cells, highly reproducible decreases in BLI were seen in an effector to target cell dose-dependent manner. When compared to results obtained from the chromium release assay, the performance of the BLI-based assay was superior, because of its robustness, increased signal-to-noise ratio, and faster kinetics. The reduced/delayed detection of cytotoxicity by the chromium release method was attributable to the association of chromium with structural components of the cell, which are released quickly by detergent solubilization but not by hypotonic lysis. We conclude that the (BLI-based measurement of cytotoxicity offers a superior non-radioactive alternative to the chromium-release assay that is more robust and quicker to perform.

  9. 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


    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.

  10. Measurement of nickel, cobalt and chromium in toy make-up by atomic absorption spectroscopy. (United States)

    Corazza, Monica; Baldo, Federica; Pagnoni, Antonella; Miscioscia, Roberta; Virgili, Annarosa


    Cosmetics should not contain more than 5 ppm of nickel, chromium or cobalt and, in order to minimize the risk of sensitization in very sensitive subjects, the target amount should be as low as 1 ppm. However, there are no published reports on the presence of these metals in toy make-up. This study analysed 52 toy make-ups using atomic absorption spectroscopy. More than 5 ppm of nickel was present in 14/52 (26.9%) samples. Chromium exceeded 5 ppm in 28/52 (53.8%) samples, with values over 1000 ppm in 3 eye shadows. Cobalt was present in amounts over 5 ppm in 5/52 (9.6%) samples. Powdery toy make-up (eye shadows) had the highest levels of metals, and "creamy" toy make-up (lip gloss and lipsticks) the lowest. Toy make-ups are potentially sensitizing items, especially for atopic children, who have a damaged skin barrier that may favour penetration of allergens.

  11. Groundwater contaminant by hexavalent chromium

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

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


    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

  13. On texture formation of chromium electrodeposits

    DEFF Research Database (Denmark)

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


    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...... established that codeposition of Cr2O3 nanoparticles is a general feature of DC chromium electrodeposition....

  14. Evaluating Foraminifera as an Archive for Seawater Chromium Isotopic Composition (United States)

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


    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

  15. p53靶位基因Wig-1——肿瘤与干细胞新的调控因子%p53 Target Gene Wig-1——A Novel Regulator of Tumors and Stem Cells

    Institute of Scientific and Technical Information of China (English)



    Wig-1 is a transcriptional target of the tumor suppressor p53 and encodes an unusual zinc-finger protein involved in posttranscriptional gene regulation. Wig-1 is expressed in almost all cell types investigated so far,with the highest levels in the brain tissue,and is enriched in stem cells as compared with more differentiated cells of the same lineage. Wig-1 binds to both long double-stranded( ds)RNA and short mi-croRNA-like dsRNA. Wig-1 acts in a positive feedback loop that stabilizes p53 mRNA through an AU-rich element ARE )in 3 'untranslated region of p53 gene. Here is to summarize current knowledge about Wig-1 and discuss its possible role in the tumor,non-neoplastic diseases and stem cells regulation,as well as its implications on p53 function.%Wig-1是抑瘤基因p53的转录调节靶位之一,编码与基因转录后水平调节相关的锌指结构蛋白.Wig-1几乎在所有类型细胞中均有表达,在脑组织中表达水平最高,在干细胞中表达水平较分化细胞高.Wig-1可结合长双链RNA(dsRNA),也可结合短的dsRNA,如microRNA.Wig-1通过结合p53基因3′非翻译区的富于AU元件稳定p53基因mRNA,正反馈调节p53基因.在此讨论Wig-1与p53功能的关系,在肿瘤、非肿瘤性疾病以及干细胞调控中的作用.

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


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


    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-...

  17. Targeted Knockdown of the Kinetochore Protein D40/Knl-1 Inhibits Human Cancer in a p53 Status-Independent Manner. (United States)

    Urata, Yuri N; Takeshita, Fumitaka; Tanaka, Hiroki; Ochiya, Takahiro; Takimoto, Masato


    The D40 gene encodes a kinetochore protein that plays an essential role in kinetochore formation during mitosis. Short inhibitory RNA against D40, D40 siRNA, has been shown to deplete the D40 protein in the human cancer cell line HeLa, which harbors wild-type p53, and this activity was followed by the significant inhibition of cell growth and induction of apoptotic cell death. The p53-null cancer cell line, PC-3M-luc, is also sensitive to the significant growth inhibition and cell death induced by D40 siRNA. The growth of PC-3M-luc tumors transplanted into nude mice was inhibited by the systemic administration of D40 siRNA and the atelocollagen complex. Furthermore, D40 siRNA significantly inhibited growth and induced apoptotic cell death in a cell line with a gain-of-function (GOF) mutation in p53, MDA-MB231-luc, and also inhibited the growth of tumors transplanted into mice when administered as a D40 siRNA/atelocollagen complex. These results indicated that D40 siRNA induced apoptotic cell death in human cancer cell lines, and inhibited their growth in vitro and in vivo regardless of p53 status. Therefore, D40 siRNA is a potential candidate anti-cancer reagent.


    Directory of Open Access Journals (Sweden)



    Full Text Available Fasting serum chromium, total cholesterol HDL-cholesterol, LDL-cholesterol, triacytglycerot and blood sugar were determined in fifty two diabetic patients with no other organic diseases anil compared with those obtained from a control group including fourty two healthy volunteers matched for age, sex ami body mass irutex (BMI. Fasting serum chromium and HDL-cholesterol were significantly lower in patients than in controls (p<0.0001 and p<0.001 respectively, but the mean triacytglycerot concentration was significantly higher in patients than in controls (p<002. Mean total cholesterol and LDL-cholesterol values were not significantly different in the two groups. Mean intake of energy, proteins, fats and chromium, estimated by the 24 hr dietary recall method were not significantly different in the two groups. We demonstrated that despite an adequate intake of chromium, the fasting serum chromium was lower in diabetic patients than in control subjects. Chromium deficiency in diabetic patients may act as a contributing factor in aggravating the disease's complications.

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

    Directory of Open Access Journals (Sweden)

    Giovana Vera


    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.

  20. Galvanic cells including cobalt-chromium alloys. (United States)

    Gjerdet, N R


    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.

  1. MicroRNA Control of p53. (United States)

    Liu, Juan; Zhang, Cen; Zhao, Yuhan; Feng, Zhaohui


    Tumor suppressor p53 plays a central role in tumor suppression. As a transcription factor, p53 mainly exerts its tumor suppressive function through transcriptional regulation of many target genes. To maintain the proper function of p53, p53 protein level and activity are exquisitely controlled by a group of positive and negative regulators in cells. Thus, p53, its regulators, and regulated genes form a complicated p53 signaling network. microRNAs (miRNAs) are a group of endogenous small non-coding RNA molecules. miRNAs play an important role in regulation of gene expression by blocking translational protein synthesis and/or degrading target mRNAs. Recent studies have demonstrated that p53 and its network are regulated by miRNAs at multiple levels. Some miRNAs regulate the level and function of p53 through directly targeting p53, whereas some other miRNAs target regulators of p53, such as MDM2 and MDM4, to indirectly regulate the activity and function of p53. On the other hand, p53 also regulates the transcriptional expression and the biogenesis of a group of miRNAs, which contributes to the tumor suppressive function of p53. p53 is the most frequently mutated gene in human cancer. Many tumor-associated mutant p53, which have "gain-of-function" activities in tumorigenesis independently of wild type p53, can regulate the expression of different miRNAs and modulate the biogenesis of specific miRNAs to promote tumorigenesis. These findings have demonstrated that miRNAs are important regulators and mediators of p53 and its signaling pathway, which highlights a pivotal role of miRNAs in the p53 network and cancer. J. Cell. Biochem. 118: 7-14, 2017. © 2016 Wiley Periodicals, Inc.

  2. SHP-2 tyrosine phosphatase inhibits p73-dependent apoptosis and expression of a subset of p53 target genes induced by EGCG



    Green tea polyphenol, epigallocatechin-3-gallate (EGCG) differentially regulates the cellular growth of cancer cells in a p53-dependent manner through apoptosis and/or cell cycle arrest. In an effort to further elucidate the mechanism of differential growth regulation by EGCG, we have investigated the role of the tyrosine phosphatase, SHP-2. Comparing the responses of mouse embryonic fibroblasts (MEFs), expressing either WT or functionally inactive/truncated SHP-2, we find that inactivation o...

  3. p53 isoforms change p53 paradigm



    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.

  4. Chromium at High Pressure (United States)

    Jaramillo, Rafael


    Chromium has long served as the archetype of spin density wave magnetism. Recently, Jaramillo and collaborators have shown that Cr also serves as an archetype of magnetic quantum criticality. Using a combination of x-ray diffraction and electrical transport measurements at high pressures and cryogenic temperatures in a diamond anvil cell, they have demonstrated that the N'eel transition (TN) can be continuously suppressed to zero, with no sign of a concurrent structural transition. The order parameter undergoes a broad regime of exponential suppression, consistent with the weak coupling paradigm, before deviating from a BCS-like ground state within a narrow but accessible quantum critical regime. The quantum criticality is characterized by mean field scaling of TN and non mean field scaling of the transport coefficients, which points to a fluctuation-induced reconstruction of the critical Fermi surface. A comparison between pressure and chemical doping as means to suppress TN sheds light on different routes to the quantum critical point and the relevance of Fermi surface nesting and disorder at this quantum phase transition. The work by Jaramillo et al. is broadly relevant to the study of magnetic quantum criticality in a physically pure and theoretically tractable system that balances elements of weak and strong coupling. [4pt] [1] R. Jaramillo, Y. Feng, J. Wang & T. F. Rosenbaum. Signatures of quantum criticality in pure Cr at high pressure. Proc. Natl. Acad. Sci. USA 107, 13631 (2010). [0pt] [2] R. Jaramillo, Y. Feng, J. C. Lang, Z. Islam, G. Srajer, P. B. Littlewood, D. B. McWhan & T. F. Rosenbaum. Breakdown of the Bardeen-Cooper-Schrieffer ground state at a quantum phase transition. Nature 459, 405 (2009).

  5. Chromium Salen Mediated Alkene Epoxidation

    DEFF Research Database (Denmark)

    Petersen, Kaare Brandt; Norrby, Per-Ola; Daly, Adrian M.;


    The mechanism of alkene epoxidation by chromium(v) oxo salen complexes has been studied by DFT and experimental methods. The reaction is compared to the closely related Mn-catalyzed process in an attempt to understand the dramatic difference in selectivity between the two systems. Overall......, the studies show that the reactions have many similarities, but also a few critical differences. In agreement with experiment, the chromium system requires a change from low- to high-spin in the catalytic cycle, whereas the manganese system can proceed either with spin inversion or entirely on the high......-spin surface. The low-spin addition of metal oxo species to an alkene leads to an intermediate which forms epoxide either with a barrier on the low-spin surface or without a barrier after spin inversion. Supporting evidence for this intermediate was obtained by using vinylcyclopropane traps. The chromium...


    Energy Technology Data Exchange (ETDEWEB)

    McCabe, D; Jeff Pike, J; Bill Wilmarth, B


    A workshop was held on January 23-24, 2007 to discuss the status of processes to leach constituents from High Level Waste (HLW) sludges at the Hanford and Savannah River Sites. The objective of the workshop was to examine the needs and requirements for the HLW flowsheet for each site, discuss the status of knowledge of the leaching processes, communicate the research plans, and identify opportunities for synergy to address knowledge gaps. The purpose of leaching of non-radioactive constituents from the sludge waste is to reduce the burden of material that must be vitrified in the HLW melter systems, resulting in reduced HLW glass waste volume, reduced disposal costs, shorter process schedules, and higher facility throughput rates. The leaching process is estimated to reduce the operating life cycle of SRS by seven years and decrease the number of HLW canisters to be disposed in the Repository by 1000 [Gillam et al., 2006]. Comparably at Hanford, the aluminum and chromium leaching processes are estimated to reduce the operating life cycle of the Waste Treatment Plant by 20 years and decrease the number of canisters to the Repository by 15,000-30,000 [Gilbert, 2007]. These leaching processes will save the Department of Energy (DOE) billions of dollars in clean up and disposal costs. The primary constituents targeted for removal by leaching are aluminum and chromium. It is desirable to have some aluminum in glass to improve its durability; however, too much aluminum can increase the sludge viscosity, glass viscosity, and reduce overall process throughput. Chromium leaching is necessary to prevent formation of crystalline compounds in the glass, but is only needed at Hanford because of differences in the sludge waste chemistry at the two sites. Improving glass formulations to increase tolerance of aluminum and chromium is another approach to decrease HLW glass volume. It is likely that an optimum condition can be found by both performing leaching and improving

  7. p53 Acetylation: Regulation and Consequences



    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...

  8. Chromium Isotopes in Marine Carbonates - an Indicator for Climatic Change? (United States)

    Frei, R.; Gaucher, C.


    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

  9. Environmental biochemistry of chromium. (United States)

    Losi, M E; Amrhein, C; Frankenberger, W T


    Chromium is a d-block transitional element with many industrial uses. It occurs naturally in various crustal materials and is discharged to the environment as industrial waste. Although it can occur in a number of oxidation states, only 3+ and 6+ are found in environmental systems. The environmental behavior of Cr is largely a function of its oxidation state. Hexavalent Cr compounds (mainly chromates and dichromates) are considered toxic to a variety of terrestrial and aquatic organisms and are mobile in soil/water systems, much more so than trivalent Cr compounds. This is largely because of differing chemical properties: Hexavalent Cr compounds are strong oxidizers and highly soluble, while trivalent Cr compounds tend to form relatively inert precipitates at near-neutral pH. The trivalent state is generally considered to be the stable form in equilibrium with most soil/water systems. A diagram of the Cr cycle in soils and water is given in Fig. 6 (Bartlett 1991). This illustration provides a summary of environmentally relevant reactions. Beginning with hexavalent Cr that is released into the environment as industrial waste, there are a number of possible fates, including pollution of soil and surface water and leaching into groundwater, where it may remain stable and, in turn, can be taken up by plants or animals, and adsorption/precipitation, involving soil colloids and/or organic matter. Herein lies much of the environmental concern associated with the hexavalent form. A portion of the Cr(VI) will be reduced to the trivalent form by inorganic electron donors, such as Fe2+ and S2-, or by bioprocesses involving organic matter. Following this conversion, Cr3+ can be expected to precipitate as oxides and hydroxides or to form complexes with numerous ligands. This fraction includes a vast majority of global Cr reserves. Soluble Cr3+ complexes, such as those formed with citrate, can undergo oxidation when they come in contact with manganese dioxide, thus reforming

  10. 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. (United States)

    Gao, Feng; Wang, Wenhui


    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.

  11. DIMP53-1: A novel small-molecule dual inhibitor of p53-MDM2/X interactions with multifunctional p53-dependent anticancer properties. (United States)

    Soares, Joana; Espadinha, Margarida; Raimundo, Liliana; Ramos, Helena; Gomes, Ana Sara; Gomes, Sara; Loureiro, Joana B; Inga, Alberto; Reis, Flávio; Gomes, Célia; Santos, Maria M M; Saraiva, Lucília


    The transcription factor p53 plays a crucial role in cancer development and dissemination, and thus p53-targeted therapies are amongst the most encouraging anticancer strategies. In human cancers with wild-type (wt) p53, its inactivation by interaction with murine double minute (MDM)2 and MDMX is a common event. Simultaneous inhibition of the p53 interaction with both MDMs is crucial to restore the tumor suppressor activity of p53. Here we describe the synthesis of the new tryptophanol-derived oxazoloisoindolinone DIMP53-1 and identify its activity as a dual inhibitor of the p53-MDM2/X interactions using a yeast-based assay. DIMP53-1 caused growth inhibition, mediated by p53 stabilization and upregulation of p53 transcriptional targets involved in cell cycle arrest and apoptosis, in wt p53-expressing tumor cells, including MDM2- or MDMX-overexpressing cells. Importantly, DIMP53-1 abolishes the p53-MDM2/X interactions by binding to p53, in human colon adenocarcinoma HCT116 cells. DIMP53-1 also inhibited the migration and invasion of HCT116 cells, and the migration and tube formation of HMVEC-D endothelial cells. Notably, in human tumor xenograft mice models, DIMP53-1 showed a p53-dependent antitumor activity through induction of apoptosis and inhibition of proliferation and angiogenesis. Finally, no genotoxicity or undesirable toxic effects were observed with DIMP53-1. In conclusion, DIMP53-1 is a novel p53 activator, which potentially binds to p53 inhibiting its interaction with MDM2 and MDMX. Although target-directed, DIMP53-1 has a multifunctional activity, targeting major hallmarks of cancer through its anti-proliferative, pro-apoptotic, anti-angiogenic, anti-invasive and anti-migratory properties. DIMP53-1 is a promising anticancer drug candidate and an encouraging starting point to develop improved derivatives for clinical application.

  12. The use of trivalent chromium bath to obtain a solar selective black chromium coating (United States)

    Survilienė, S.; Češūnienė, A.; Juškėnas, R.; Selskienė, A.; Bučinskienė, D.; Kalinauskas, P.; Juškevičius, K.; Jurevičiūtė, I.


    Black chromium coatings were electrodeposited from a trivalent chromium bath using a ZnO additive as a second main component. Black chromium was electrodeposited on steel and copper plates and substrates plated with bright nickel prior to black chromium electrodeposition. The black chromium coatings were characterized by XRD and SEM. The XRD data suggest that the phase structure of black chromium may be defined as a zinc solid solution in chromium or a chromium solid solution in zinc depending on the chromium/zinc ratio in the deposit. The role of substrate finish was evaluated through the corrosion resistance and reflectance of black chromium. According to corrosion tests the samples plated with bright nickel prior to black chromium deposition have shown the highest corrosion resistance. The electrodeposited black chromium possesses good optical properties for the absorption of solar energy. The absorption coefficient of black chromium was found to be over 0.99 for the samples obtained without the Ni undercoat and below 0.99 for those obtained with the use of Ni undercoat. However, the use of nickel undercoat before black chromium plating is recommended because it remarkably improves the corrosion resistance of samples.

  13. Chromium isotope variations

    DEFF Research Database (Denmark)

    D'Arcy, Joan Mary

    is incorporated into carbonates. Hence, ancient carbonates can potentially record the Cr isotopic composition (δ53Cr ‰) of seawater in the geological past. Reliable application and interpretation of this proxy requires a detailed knowledge about processes that fractionate Cr on the Earth’s surface...... deposited during the Early Ordovician — a time of known redox instability in ancient oceans – exhibit a significant positive Cr isotope excursion of +0.5‰. This excursion is interpreted as the reductive drawn down of dissolved Cr in seawater in response to the development of a proximal anoxic sink......, and the quantification the Cr isotope composition of major Cr fluxes into and out of ocean. This thesis adds to the current knowledge of the Cr isotope system and is divided into two studies. The focus of the first study was to determine what processes control the Cr isotopic compositionof river water and to quantify...

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


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


    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 ...

  15. Lupeol induces p53 and cyclin-B-mediated G2/M arrest and targets apoptosis through activation of caspase in mouse skin. (United States)

    Nigam, Nidhi; Prasad, Sahdeo; George, Jasmine; Shukla, Yogeshwer


    Lupeol, present in fruits and medicinal plants, is a biologically active compound that has been shown to have various pharmacological properties in experimental studies. In the present study, we demonstrated the modulatory effect of lupeol on 7,12-dimethylbenz[a]anthracene (DMBA)-induced alterations on cell proliferation in the skin of Swiss albino mice. Lupeol treatment showed significant (p < 0.05) preventive effects with marked inhibition at 48, 72, and 96 h against DMBA-mediated neoplastic events. Cell-cycle analysis showed that lupeol-induced G2/M-phase arrest (16-37%) until 72 h, and these inhibitory effects were mediated through inhibition of the cyclin-B-regulated signaling pathway involving p53, p21/WAF1, cdc25C, cdc2, and cyclin-B gene expression. Further lupeol-induced apoptosis was observed, as shown by an increased sub-G1 peak (28%) at 96 h, with upregulation of bax and caspase-3 genes and downregulation of anti-apoptotic bcl-2 and survivin genes. Thus, our results indicate that lupeol has novel anti-proliferative and apoptotic potential that may be helpful in designing strategies to fight skin cancer.

  16. Loss of the p53/p63 Target PERP is an Early Event in Oral Carcinogenesis and Correlates with Higher Rate of Local Relapse (United States)

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


    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

  17. 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


    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.

  18. Study on anaerobic treatment of wastewater containing hexavalent chromium. (United States)

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


    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.

  19. Study on anaerobic treatment of wastewater containing hexavalent chromium* (United States)

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


    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

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

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


    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.

  1. Metabolic regulation by p53 family members. (United States)

    Berkers, Celia R; Maddocks, Oliver D K; Cheung, Eric C; Mor, Inbal; Vousden, Karen H


    The function of p53 is best understood in response to genotoxic stress, but increasing evidence suggests that p53 also plays a key role in the regulation of metabolic homeostasis. p53 and its family members directly influence various metabolic pathways, enabling cells to respond to metabolic stress. These functions are likely to be important for restraining the development of cancer but could also have a profound effect on the development of metabolic diseases, including diabetes. A better understanding of the metabolic functions of p53 family members may aid in the identification of therapeutic targets and reveal novel uses for p53-modulating drugs.

  2. 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


    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...

  3. 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: [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)


    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.

  4. p53 Acetylation: Regulation and Consequences

    Directory of Open Access Journals (Sweden)

    Sara M. Reed


    Full Text Available 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.

  5. 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


    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.

  6. Sonoassisted microbial reduction of chromium. (United States)

    Kathiravan, Mathur Nadarajan; Karthick, Ramalingam; Muthu, Naggapan; Muthukumar, Karuppan; Velan, Manickam


    This study presents sonoassisted microbial reduction of hexavalent chromium (Cr(VI)) using Bacillus sp. isolated from tannery effluent contaminated site. The experiments were carried out with free cells in the presence and absence of ultrasound. The optimum pH and temperature for the reduction of Cr(VI) by Bacillus sp. were found to be 7.0 and 37 degrees C, respectively. The Cr(VI) reduction was significantly influenced by the electron donors and among the various electron donors studied, glucose offered maximum reduction. The ultrasound-irradiated reduction of Cr(VI) with Bacillus sp. showed efficient Cr(VI) reduction. The percent reduction was found to increase with an increase in biomass concentration and decrease with an increase in initial concentration. The changes in the functional groups of Bacillus sp., before and after chromium reduction were observed with FTIR spectra. Microbial growth was described with Monod and Andrews model and best fit was observed with Andrews model.

  7. Deconstructing p53 transcriptional networks in tumor suppression. (United States)

    Bieging, Kathryn T; Attardi, Laura D


    p53 is a pivotal tumor suppressor that induces apoptosis, cell-cycle arrest and senescence in response to stress signals. Although p53 transcriptional activation is important for these responses, the mechanisms underlying tumor suppression have been elusive. To date, no single or compound mouse knockout of specific p53 target genes has recapitulated the dramatic tumor predisposition that characterizes p53-null mice. Recently, however, analysis of knock-in mice expressing p53 transactivation domain mutants has revealed a group of primarily novel direct p53 target genes that may mediate tumor suppression in vivo. We present here an overview of well-known p53 target genes and the tumor phenotypes of the cognate knockout mice, and address the recent identification of new p53 transcriptional targets and how they enhance our understanding of p53 transcriptional networks central for tumor suppression.

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

    Lifescience Database Archive (English)

    Full Text Available Trp53 Embryo,Embryonic fibroblast + mm9,

  9. Status quo of p53 in the treatment of tumors. (United States)

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


    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.

  10. Inoculation of chromium white cast iron

    Directory of Open Access Journals (Sweden)

    D. Kopyciński


    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.

  11. 表没食子儿茶素没食子酸酯通过调控P53/miR-34a 抑制鼻咽癌细胞的增殖%Inhibitory role of epigallocatechin-3-gallate in proliferation of human na-sopharyngeal carcinoma cells by targeting P53/miR-34a

    Institute of Scientific and Technical Information of China (English)

    李彬彬; 万郑; 孔霞; 廖丹; 王籽又; 黄国良


    AIM:To study the effect of epigallocatechin-3-gallate (EGCG) on the proliferation of human naso-pharyngeal carcinoma ( NPC) cells, and to explore its mechanism by targeting miR-34a.METHODS: Nasopharyngeal carcinoma CNE-2Z cells were treated with various concentrations of EGCG .The ability of cell proliferation was detected by CCK-8 assay, 5-ethynyl-2-deoxyuridine (EdU) incorporation assay and colony-forming assay.The cell cycle distributions were analyzed by flow cytometry .The protein levels of P53 and Notch1 were detected by Western blot .The expression of miR-34a and Notch1 mRNA was measured by real-time PCR.RESULTS:EGCG effectively inhibited the proliferation and colony formation of CNE-2Z cells in a dose-dependent manner , which was related to its induction of cell cycle arrest at G 0/G1 phase.The expression of P53 and miR-34a in CNE-2Z cells was significantly increased after treated with EGCG , while the expression of Notch1 at mRNA and protein levels was markedly suppressed .CONCLUSION:EGCG induces cell cycle arrest and suppresses cell proliferation by regulating the P 53/miR-34a/Notch1 pathway in NPC cells.%目的:观察表没食子儿茶素没食子酸酯( EGCG )对鼻咽癌细胞增殖的影响,并以微小RNA-34 a (miR-34a)为靶点探讨其作用机制。方法:不同浓度的EGCG处理CNE-2Z细胞,CCK-8法、EdU染色法和平板克隆形成实验检测细胞增殖能力的改变;流式细胞术检测细胞周期分布的改变;Western blot 检测P53和Notch1蛋白水平的变化;real-time PCR检测miR-34a和Notch1 mRNA的表达。结果:EGCG处理后,CNE-2Z细胞的增殖受到明显抑制,克隆形成能力降低,细胞周期阻滞于G0/G1期,呈剂量依赖关系;随着EGCG浓度增高,P53和miR-34a的表达水平明显上调,而其下游Notch1 mRNA和蛋白的表达水平则明显下降。结论:EGCG可能通过调控P53/miR-34a/Notch1通路诱导细胞周期阻滞,抑制鼻咽癌细胞增殖。

  12. The influence of substrate temperature on the tribo- mechanical properties of chromium nitride thin films (United States)

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


    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.

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

    Institute of Scientific and Technical Information of China (English)


    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.

  14. 29 CFR 1915.1026 - Chromium (VI). (United States)


    ... system dysfunction; any history of asthma, dermatitis, skin ulceration, or nasal septum perforation; and... is present or is likely to be present from skin or eye contact with chromium (VI), the employer shall... cleaned in a manner that minimizes skin or eye contact with chromium (VI) and effectively prevents...

  15. 29 CFR 1926.1126 - Chromium (VI). (United States)


    ... system dysfunction; any history of asthma, dermatitis, skin ulceration, or nasal septum perforation; and... is present or is likely to be present from skin or eye contact with chromium (VI), the employer shall... cleaned in a manner that minimizes skin or eye contact with chromium (VI) and effectively prevents...

  16. 29 CFR 1910.1026 - Chromium (VI). (United States)


    ... activity involving chromium cannot release dusts, fumes, or mists of chromium (VI) in concentrations at or... currents that prevent the LEVs from performing efficiently. The use of fans has a similar effect. Industry... and positioning of cross drafts, fans, doors, windows, partitions and process equipment that...

  17. Berberine alters epigenetic modifications, disrupts microtubule network, and modulates HPV-18 E6-E7 oncoproteins by targeting p53 in cervical cancer cell HeLa: a mechanistic study including molecular docking. (United States)

    Saha, Santu Kumar; Khuda-Bukhsh, Anisur Rahman


    Increased evidence of chemo-resistance, toxicity and carcinogenicity necessitates search for alternative approaches for determining next generation cancer therapeutics and targets. We therefore tested the efficacy of plant alkaloid berberine on human papilloma virus (HPV) -18 positive cervical cancer cell HeLa systematically-involving certain cellular, viral and epigenetic factors. We observed disruptions of microtubule network and changes in membrane topology due to berberine influx through confocal and atomic force microscopies (AFM). We examined nuclear uptake, internucleosomal DNA damages, mitochondrial membrane potential (MMP) alterations and cell migration assays to validate possible mode of cell death events. Analytical data on interactions of berberine with pBR322 through fourier transform infrared (FTIR) and gel migration assay strengthen berberine׳s biologically significant DNA binding abilities. We measured cellular uptake, DNA ploidy and DNA strand-breaks through fluorescence activated cell sorting (FACS). To elucidate epigenetic modifications, in support of DNA binding associated processes, if any, we conducted methylation-specific restriction enzyme (RE) assay, methylation specific-PCR (MSP) and expression studies of histone proteins. We also analyzed differential interactions and localization of cellular tumor suppressor p53 and viral oncoproteins HPV-18 E6-E7 through siRNA approach. We further made in-silico approaches to determine possible binding sites of berberine on histone proteins. Overall results indicated cellular uptake of berberine through cell membrane depolarization causing disruption of microtubule networks and its biological DNA binding abilities that probably contributed to epigenetic modifications. Results of modulation in p53 and viral oncoproteins HPV-18 E6-E7 by berberine further proved its potential as a promising chemotherapeutic agent in cervical cancer.

  18. p53 regulates the cardiac transcriptome (United States)

    Mak, Tak W.; Hauck, Ludger; Grothe, Daniela; Billia, Filio


    The tumor suppressor Trp53 (p53) inhibits cell growth after acute stress by regulating gene transcription. The mammalian genome contains hundreds of p53-binding sites. However, whether p53 participates in the regulation of cardiac tissue homeostasis under normal conditions is not known. To examine the physiologic role of p53 in adult cardiomyocytes in vivo, Cre-loxP–mediated conditional gene targeting in adult mice was used. Genome-wide transcriptome analyses of conditional heart-specific p53 knockout mice were performed. Genome-wide annotation and pathway analyses of >5,000 differentially expressed transcripts identified many p53-regulated gene clusters. Correlative analyses identified >20 gene sets containing more than 1,000 genes relevant to cardiac architecture and function. These transcriptomic changes orchestrate cardiac architecture, excitation-contraction coupling, mitochondrial biogenesis, and oxidative phosphorylation capacity. Interestingly, the gene expression signature in p53-deficient hearts confers resistance to acute biomechanical stress. The data presented here demonstrate a role for p53, a previously unrecognized master regulator of the cardiac transcriptome. The complex contributions of p53 define a biological paradigm for the p53 regulator network in the heart under physiological conditions. PMID:28193895

  19. TP53 dysfunction in diffuse large B-cell lymphoma. (United States)

    Lu, Ting-Xun; Young, Ken H; Xu, Wei; Li, Jian-Yong


    The aberrations of TP53 gene and dysregulation of the TP53 pathway are important in the pathogenesis of many human cancers, including malignant lymphomas, especially for diffuse large B cell lymphoma (DLBCL). By regulating many downstream target genes or molecules, TP53 governs major defenses against tumor growth and promotes cellular DNA repair, apoptosis, autophagy, cell cycle arrest, signaling, transcription, immune or inflammatory responses and metabolism. Dysfunction of TP53, including microRNA regulations, copy number alterations of TP53 pathway and TP53 itself, dysregulation of TP53 regulators, and somatic mutations by abnormal TP53 function modes, play an important role in lymphoma generation, progression and invasion. The role of TP53 in DLBCL has been widely explored recently. In this review, we summarized recent advances on different mechanisms of TP53 in DLBCL and new therapeutic approaches to overcome TP53 inactivation.

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

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


    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. Compliance of a cobalt chromium coronary stent alloy – the COVIS trial

    Directory of Open Access Journals (Sweden)

    Schwinger Robert HG


    Full Text Available Abstract Background Cobalt chromium coronary stents are increasingly being used in percutaneous coronary interventions. There are, however, no reliable data about the characteristics of unfolding and visibility of this stent alloy in vivo. The aim of this study is to compare cobalt chromium coronary stents with conventional stainless steel stents using intracoronary ultrasound. Methods Twenty de novo native coronary stenoses ≤ 20 mm in length (target vessel reference diameter ≥ 2.5 and ≤ 4.0 mm received under sequential intracoronary ultrasound either a cobalt chromium stent (Multi-Link Vision®; n = 10 or a stainless steel stent (Multi-Link Zeta®; n = 10. Results For optimal unfolding, the cobalt chromium stent requires a higher balloon deployment pressure (13.90 ± 2.03 atm than the stainless steel stent (11.50 ± 2.12 atm. Furthermore, the achieved target vessel diameter of the cobalt chromium stent (Visibility-Index QCA/IVUS Multi-Link Vision®1.13 / Multi-Link Zeta® 1.04 is more easily overrated by Quantitative Coronary Analysis. Conclusion These data indicate that stent material-specific recommendations for optimal implantation pressure and different stent material with an equal design should both be considered in interpreting QCA-analysis.

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

    Lifescience Database Archive (English)

    Full Text Available lin-53 Larvae + ce10 ...

  3. 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)


    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.

  4. Chromium Isotopes Record Fluctuations in Precambrian Biospheric Oxygenation (United States)

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


    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.

  5. Synthesis of Chromium (Ⅲ) 5-aminosalicylate

    Institute of Scientific and Technical Information of China (English)

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


    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 .

  6. 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;


    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...

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

    DEFF Research Database (Denmark)

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


    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...

  8. Leaching of chromium from chromium contaminated soil: Speciation study and geochemical modeling

    Directory of Open Access Journals (Sweden)

    Anđelković Darko H.


    Full Text Available Distribution of chromium between soil and leachate was monitored. A natural process of percolating rainwater through the soil was simulated in the laboratory conditions and studied with column leaching extraction. Migration of chromium in the soil is conditioned by the level of chromium soil contamination, the soil organic matter content, and rainwater acidity. Chromium (III and chromium(VI were determined by spectrophotometric method with diphenilcarbazide in acidic media. Comparing the results of chromium speciation in leachate obtained by experimental model systems and geochemical modelling calculations using Visual MINTEQ model, a correlation was observed regarding the influence of the tested parameters. Leachate solutions showed that the concentration of Cr depended on the organic matter content. The influence of pH and soil organic matter content is in compliance after its definition through experimental and theoretical way. The computer model - Stockholm Humic Model used to evaluate the leaching results corresponded rather well with the measured values.

  9. Chromium increases pancreatic metallothionein in the rat. (United States)

    Solis-Heredia, M J; Quintanilla-Vega, B; Sierra-Santoyo, A; Hernández, J M; Brambila, E; Cebrián, M E; Albores, A


    The ability of chromium (Cr) salts to increase metallothionein (MT) levels in rat liver, kidney and pancreas, and its relationship with the presence of toxic effects are reported here. Rats were injected subcutaneously with 0, 10, 20, 30, 40, or 50 mg K2Cr2O7/kg and sacrificed 24 h later. Total Cr accumulation followed a dose-dependent pattern, levels in kidney being higher than those in liver or pancreas, suggesting different tissue bioavailabilities and accumulation patterns. Cr(IV) administration resulted in a tissue-specific MT induction: pancreas and liver showed five- and 3.5-fold MT increases, respectively; no increase was observed in the kidney. A positive correlation was observed between zinc and MT concentrations in liver, and between total Cr and MT concentrations in pancreas. Serum alpha-amylase activity showed a dose-dependent increase starting from 20 mg/kg, whereas serum glucose levels increased at doses higher than 30 mg/kg. Serum aspartate aminotransferase and alanine aminotransferase activities were increased in a dose-dependent manner, from 20 and 30 mg/kg, respectively. Our results showed that treatment with Cr(VI) can induce MT synthesis in pancreas and suggests a subsequent binding of Cr to MT. Also, pancreas is a target organ for Cr toxicity, and the usefulness of alpha-amylase activity as a sensitive biomarker of Cr toxicity in human exposed populations merits further study.

  10. 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......Chromium (Cr) is a redox sensitive element potentially capable of tracing fine-scale fluctuations of the oxygenation of Earth’s early surface environments and seawater. The Cr isotope composition of carbonates could perhaps be used as paleo-redox proxy to elucidate changes in the geological past...... related to the rise of oxygen and the evolution of the biosphere. However, before the Cr isotopesystem can be applied to faithfully delineate paleo-environmental changes, careful assessment of the signal robustness and a thorough understanding of the Cr cycle in Earth system processes is necessary...

  11. Chromium (VI) adsorption on boehmite

    Energy Technology Data Exchange (ETDEWEB)

    Granados-Correa, F. [Instituto Nacional de Investigaciones Nucleares, Apartado Postal 18-1027 Col., Escandon, Delegacion Miguel Hidalgo, C.P. 11801 Mexico, D.F. (Mexico)], E-mail:; Jimenez-Becerril, J. [Instituto Nacional de Investigaciones Nucleares, Apartado Postal 18-1027 Col., Escandon, Delegacion Miguel Hidalgo, C.P. 11801 Mexico, D.F. (Mexico)


    Boehmite was synthesized and characterized in order to study the adsorption behavior and the removal of Cr(VI) ions from aqueous solutions as a function of contact time, initial pH solution, amount of adsorbent and initial metal ion concentration, using batch technique. Adsorption data of Cr(VI) on the boehmite were analyzed according to Freundlich, Langmuir and Dubinin-Radushkevich (D-R) adsorption models. Thermodynamic parameters for the adsorption system were determinated at 293, 303, 313 and 323 K temperatures. The kinetic values and thermodynamic parameters from the adsorption process show that the Cr(VI) ions adsorption on boehmite is an endothermic and spontaneous process. These results show that the boehmite could be considered as a potential adsorbent for chromium ions in aqueous solutions.

  12. Mechanical properties of metal-ceramic systems from nickel-chromium and cobalt-chromium alloys

    Directory of Open Access Journals (Sweden)

    Mirković Nemanja


    Full Text Available Background/Aim. Metal-ceramic bond strength and alloys' elastic modulus clearly determine the potential of alloy application, because the ceramic integrity during mastication depends on these two characteristics. The aim of this study was to evaluate metal-ceramic bond strength and elastic modulus of cobalt-chromium alloys in making porcelainfused- to-metal restorations, regarding the application of the most frequent nickel-chromium alloy. Methods. The research was performed as an experimental study. Six metalceramic samples were made from nickel-chromium alloy (Wiron 99 and cobalt-chromium alloy (Wirobond C, according to the manufactures manuals and instructions from ISO 9693: 1996. Three-point bending test was performed up to the ceramic fracture. The fracture load was measured on an universal testing machine (Zwick, type 1464, with cross-head speed of 0,05mm/min. Results. The results of this study confirmed the significant differences between the metal-ceramic bond strength (p < 0.01 and elastic modulus (p < 0.001 of nickel-chromium and cobalt-chromium alloys, where cobalt-chromium alloys showed higher values for both tested parameters. Conclusion. Cobalt-chromium metal-ceramic alloys can successfully replace nickel-chromium alloys, especially for fabrication of long-span metal-ceramic bridges due to the great flexural strength.


    Institute of Scientific and Technical Information of China (English)

    Suyuan Yu


    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.

  14. Localized Corrosion of Chromium Coated Steel

    NARCIS (Netherlands)

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


    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.


    Directory of Open Access Journals (Sweden)

    M. Ghiasseddin


    Full Text Available Hazards of soluable hexa and trivalent chromium have been documented by many investigators. But there was no information regarding safety of about 5000 workers at exposure risk to chromium in 600 primitive electroplating work shops of Tehran. During this study more than 70% of work shops were inactive due to some of their own problems. Out of active plants those that were relatively more cooperative 43 manual and 3 semi automatic were investigated for chromium concentration both by personal and environmental Sampling. The Samples were analyzed by AAS and cholormetry. In 30% of personal and 40% of environmental samples both total and Cr+6 were higher than ACGIH’S TLV. In one of semiautomatic plant Cr=6 was as high as 0.71 mg/m.3.Regarding injuries, following observations were made: Nasal wound 85%, skin irritation 73% , Dermatitis 35% and some other chromium related injuries including 2 cases of Septum perforations.

  16. Potentiometry: A Chromium (III) -- EDTA Complex (United States)

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


    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)

  17. 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


    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

  18. 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


    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

  19. Permeation of chromium salts through human skin in vitro

    DEFF Research Database (Denmark)

    Gammelgaard, Bente; Fullerton, A; Avnstorp, C


    Chromium permeation studies were performed on full thickness human skin in diffusion cells. All samples were analysed for the total chromium content by graphite furnace Zeeman-corrected atomic absorption spectrometry. Some samples were analysed by an ion chromatographic method permitting...... the simultaneous determination of Cr(VI) and Cr(III) as well. The amounts of chromium found in all skin layers were significantly higher when potassium dichromate was applied to the skin compared with chromium chloride or chromium nitrate. Chromium could only be detected in the recipient phase after application...... 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...

  20. The structures of complexes of Chromium(III with cystine and ethylglycine

    Directory of Open Access Journals (Sweden)

    Lina A. Chernushenko


    Full Text Available It has been investigated the electronic spectra of complex compounds of chromium(III with amino acids as bidentate coordinated in compound (I and as monodentate coordinated in compound (II in solution. Three-ethyl glycinate and three-cystinate have the octahedral structure. Two bands of transition were observed in the visible part of the spectrum 4Т1g¬4A2g  and 4Т2g¬4A2g, one band of transition was observed in UV- spectrum, 4Т1g(Р¬4A2g. It was submitted the results of calculations of crystal field parameters: Dq = 1790 cm-1, В = 560.57 cm-1 and b = 0.54 for compound (I, Dq = 1786 cm-1, В = 504.53sm-1 and b = 0.49 for compound (II. The computer three-dimensional models of structure of such chromium(III complexes as three-cystinate chromium (III and three-chromium glycinate were created. Quantum-chemical modeling programs Chemcraft and WinGAMESS were used. Angles and bond lengths were calculated.

  1. The chromium isotope composition of reducing and oxic marine sediments (United States)

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


    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

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

    Lifescience Database Archive (English)

    Full Text Available,,,,http://dbarchive.biosciencedbc

  3. Direct access to macroporous chromium nitride and chromium titanium nitride with inverse opal structure. (United States)

    Zhao, Weitian; DiSalvo, Francis J


    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.

  4. The Key Technique of Manufacture of Dense Chromium Sesquioxide Refractories

    Institute of Scientific and Technical Information of China (English)

    LIMaoqiang; ZHANGShuying; 等


    Dense chromium sesquioxide refractories have widely been used in the kilns for making alkai-free and anti-alkali glass fibers due to their excellent re-sistance to molten glasses.Densifications of chromium sesquioxide during sintering can be blocked by evaporation of chromium trioxide derived from oxidation at high temperature,In this paper the mech-anism of sintering chromium oxide and the process-ing technique for making dense chromium sesquiox-ide refractories are discussed .A process in laboratory scale for making dense chromium sesquioxide bricks is demonstrated.

  5. Mdm2 RING mutation enhances p53 transcriptional activity and p53-p300 interaction.

    Directory of Open Access Journals (Sweden)

    Hilary V Clegg

    Full Text Available The p53 transcription factor and tumor suppressor is regulated primarily by the E3 ubiquitin ligase Mdm2, which ubiquitinates p53 to target it for proteasomal degradation. Aside from its ubiquitin ligase function, Mdm2 has been believed to be capable of suppressing p53's transcriptional activity by binding with and masking the transactivation domain of p53. The ability of Mdm2 to restrain p53 activity by binding alone, without ubiquitination, was challenged by a 2007 study using a knockin mouse harboring a single cysteine-to-alanine point mutation (C462A in Mdm2's RING domain. Mouse embryonic fibroblasts with this mutation, which abrogates Mdm2's E3 ubiquitin ligase activity without affecting its ability to bind with p53, were unable to suppress p53 activity. In this study, we utilized the Mdm2(C462A mouse model to characterize in further detail the role of Mdm2's RING domain in the control of p53. Here, we show in vivo that the Mdm2(C462A protein not only fails to suppress p53, but compared to the complete absence of Mdm2, Mdm2(C462A actually enhances p53 transcriptional activity toward p53 target genes p21/CDKN1A, MDM2, BAX, NOXA, and 14-3-3σ. In addition, we found that Mdm2(C462A facilitates the interaction between p53 and the acetyltransferase CBP/p300, and it fails to heterodimerize with its homolog and sister regulator of p53, Mdmx, suggesting that a fully intact RING domain is required for Mdm2's inhibition of the p300-p53 interaction and for its interaction with Mdmx. These findings help us to better understand the complex regulation of the Mdm2-p53 pathway and have important implications for chemotherapeutic agents targeting Mdm2, as they suggest that inhibition of Mdm2's E3 ubiquitin ligase activity may be sufficient for increasing p53 activity in vivo, without the need to block Mdm2-p53 binding.

  6. 53Mn-53Cr dating of fayalite formation in the CV3 chondrite Mokoia: evidence for asteroidal alteration. (United States)

    Hutcheon, I D; Krot, A N; Keil, K; Phinney, D L; Scott, E R


    Fayalite grains in chondrules in the oxidized, aqueously altered CV3 chondrite Mokoia have large excesses of radiogenic chromium-53. These excesses indicate the in situ decay of short-lived manganese-53 (half-life = 3.7 million years) and define an initial 53Mn/55Mn ratio of 2.32 (+/-0.18) x 10(-6). This ratio is comparable to values for carbonates in CI and CM chondrites and for several classes of differentiated meteorites. Mokoia fayalites formed 7 to 16 million years after Allende calcium-aluminum-rich inclusions, during hydrothermal activity on a geologically active asteroid after chondritic components had ceased forming in the solar nebula.

  7. Synthesis of a new complex Chromium (Ⅲ) 2-mercaptonicotinate

    Institute of Scientific and Technical Information of China (English)

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


    Chromium is an essential trace element for mammals[1-3].Diabetes is a chronic disease with major health consequence. Studies show 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)[4]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)[5]So there is potential for the design of new chromium drugs[6].Chromium compounds have been used in medicine for centuries and there is potential for the design of new chromium drugs.2-Mercaptonicotinic acid(MN) displays the interesting biological activity. Chromium( Ⅲ )2-mercaptonicotinate is a common and effective biologically active form of Chromium. The test of biological activity indicated that may be useful in treating of diabetes. In this paper, we reported the The synthesis route is as follow:The structure of the complex has been characterized by IR, elemental analysis, MS,atomic absorption spectroscopy, X-ray powder diffraction and TG-DTA analysis.They indicate that the structure of Chromium 2-mercaptonicotinate.HPLC is used for determination of the purity. Studies show that the complex has a good biological activity for supplement tiny dietary chromium,lowering blood glucose levels, lowering serum lipid levels and increasing lean body mass.

  8. TP53 — EDRN Public Portal (United States)

    TP53, also widely known as p53, acts as a tumor suppressor in many tumor types, responding to diverse cellular stresses to regulate target genes that induce cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. It is involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. p53 protein is expressed at low level in normal cells and at a high level in a variety of transformed cell lines, where it's believed to contribute to transformation and malignancy. p53 is a DNA-binding protein containing transcription activation, DNA-binding, and oligomerization domains. It is postulated to bind to a p53-binding site and activate expression of downstream genes that inhibit growth and/or invasion, and thus function as a tumor suppressor. Mutants of p53 that frequently occur in a number of different human cancers fail to bind the consensus DNA binding site, and hence cause the loss of tumor suppressor activity. Multiple p53 variants due to alternative promoters and multiple alternative splicing have been found. These variants encode distinct isoforms, which can regulate p53 transcriptional activity.

  9. Reactivation of mutant p53 by capsaicin, the major constituent of peppers



    Background Mutations in the p53 oncosuppressor gene are highly frequent in human cancers. These alterations are mainly point mutations in the DNA binding domain of p53 and disable p53 from transactivating target genes devoted to anticancer activity. Mutant p53 proteins are usually more stable than wild-type p53 and may not only impair wild-type p53 activity but also acquire pro-oncogenic functions. Therefore, targeting mutant p53 to clear the hyperstable proteins or change p53 conformation to...

  10. Serum chromium levels in gestational diabetes mellitus

    Directory of Open Access Journals (Sweden)

    P G Sundararaman


    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.

  11. Surface Chemistry and Spectroscopy of Chromium in Inorganic Oxides

    NARCIS (Netherlands)

    Weckhuysen, B.M.; Wachs, I.E.; Schoonheydt, R.A.


    Focuses on the surface chemistry and spectroscopy of chromium in inorganic oxides. Characterization of the molecular structures of chromium; Mechanics of hydrogenation-dehydrogenation reactions; Mobility and reactivity on oxidic surfaces.

  12. Optimized p53 immunohistochemistry is an accurate predictor of TP53 mutation in ovarian carcinoma. (United States)

    Köbel, Martin; Piskorz, Anna M; Lee, Sandra; Lui, Shuhong; LePage, Cecile; Marass, Francesco; Rosenfeld, Nitzan; Mes Masson, Anne-Marie; Brenton, James D


    TP53 mutations are ubiquitous in high-grade serous ovarian carcinomas (HGSOC), and the presence of TP53 mutation discriminates between high and low-grade serous carcinomas and is now an important biomarker for clinical trials targeting mutant p53. p53 immunohistochemistry (IHC) is widely used as a surrogate for TP53 mutation but its accuracy has not been established. The objective of this study was to test whether improved methods for p53 IHC could reliably predict TP53 mutations independently identified by next generation sequencing (NGS). Four clinical p53 IHC assays and tagged-amplicon NGS for TP53 were performed on 171 HGSOC and 80 endometrioid carcinomas (EC). p53 expression was scored as overexpression (OE), complete absence (CA), cytoplasmic (CY) or wild type (WT). p53 IHC was evaluated as a binary classifier where any abnormal staining predicted deleterious TP53 mutation and as a ternary classifier where OE, CA or WT staining predicted gain-of-function (GOF or nonsynonymous), loss-of-function (LOF including stopgain, indel, splicing) or no detectable TP53 mutations (NDM), respectively. Deleterious TP53 mutations were detected in 169/171 (99%) HGSOC and 7/80 (8.8%) EC. The overall accuracy for the best performing IHC assay for binary and ternary prediction was 0.94 and 0.91 respectively, which improved to 0.97 (sensitivity 0.96, specificity 1.00) and 0.95 after secondary analysis of discordant cases. The sensitivity for predicting LOF mutations was lower at 0.76 because p53 IHC detected mutant p53 protein in 13 HGSOC with LOF mutations. CY staining associated with LOF was seen in 4 (2.3%) of HGSOC. Optimized p53 IHC can approach 100% specificity for the presence of TP53 mutation and its high negative predictive value is clinically useful as it can exclude the possibility of a low-grade serous tumour. 4.1% of HGSOC cases have detectable WT staining while harboring a TP53 LOF mutation, which limits sensitivity for binary prediction of mutation to 96%.

  13. Residual Chromium in Leather by Instrumental Neutron Activation Analysis


    S. Okoh; I. O. Okunade; D. J. Adeyemo; Ahmed, Y A; A. A. Audu; E. Amali


    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 irrad...

  14. Hexavalent and trivalent chromium in leather: What should be done? (United States)

    Moretto, Angelo


    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. 21 CFR 73.1015 - Chromium-cobalt-aluminum oxide. (United States)


    ... 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...

  16. p53 protein aggregation promotes platinum resistance in ovarian cancer. (United States)

    Yang-Hartwich, Y; Soteras, M G; Lin, Z P; Holmberg, J; Sumi, N; Craveiro, V; Liang, M; Romanoff, E; Bingham, J; Garofalo, F; Alvero, A; Mor, G


    High-grade serous ovarian carcinoma (HGSOC), the most lethal gynecological cancer, often leads to chemoresistant diseases. The p53 protein is a key transcriptional factor regulating cellular homeostasis. A majority of HGSOCs have inactive p53 because of genetic mutations. However, genetic mutation is not the only cause of p53 inactivation. The aggregation of p53 protein has been discovered in different types of cancers and may be responsible for impairing the normal transcriptional activation and pro-apoptotic functions of p53. We demonstrated that in a unique population of HGSOC cancer cells with cancer stem cell properties, p53 protein aggregation is associated with p53 inactivation and platinum resistance. When these cancer stem cells differentiated into their chemosensitive progeny, they lost tumor-initiating capacity and p53 aggregates. In addition to the association of p53 aggregation and chemoresistance in HGSOC cells, we further demonstrated that the overexpression of a p53-positive regulator, p14ARF, inhibited MDM2-mediated p53 degradation and led to the imbalance of p53 turnover that promoted the formation of p53 aggregates. With in vitro and in vivo models, we demonstrated that the inhibition of p14ARF could suppress p53 aggregation and sensitize cancer cells to platinum treatment. Moreover, by two-dimensional gel electrophoresis and mass spectrometry we discovered that the aggregated p53 may function uniquely by interacting with proteins that are critical for cancer cell survival and tumor progression. Our findings help us understand the poor chemoresponse of a subset of HGSOC patients and suggest p53 aggregation as a new marker for chemoresistance. Our findings also suggest that inhibiting p53 aggregation can reactivate p53 pro-apoptotic function. Therefore, p53 aggregation is a potential therapeutic target for reversing chemoresistance. This is paramount for improving ovarian cancer patients' responses to chemotherapy, and thus increasing their

  17. 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


    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

  18. TP53 dysfunction in CLL: Implications for prognosis and treatment. (United States)

    Te Raa, Gera D; Kater, Arnon P


    Despite the availability of novel targeted agents, TP53 defects remain the most important adverse prognostic factor in chronic lymphocytic leukemia (CLL). Detection of deletion of TP53 locus (17p deletion) by fluorescent in situ hybridization (FISH) has become standard and performed prior to every line of treatment as the incidence dramatically increases as relapses occur. As monoallelic mutations of TP53 equally affect outcome, novel methods are being developed to improve detection of TP53 defects and include next-generation sequencing (NGS) and functional assays. TP53 defects highly affect outcome of immunochemotherapy but also alter response durations of tyrosine kinase inhibitors. Although BCR-targeting agents and Bcl-2-inhibitos have achieved durable responses in some patients with TP53 defects, long-term follow-up is currently lacking. In this review biological and clinical consequences of TP53 dysfunction as well as applicability of currently available methods to detect TP53 defects are described. In addition, proposed novel therapeutic strategies specifically for patients with TP53 dysfunction are discussed. In summary, the only curative treatment option for TP53-defective CLL is still allogeneic hematopoietic stem cell transplantation. Other treatment strategies such as rationale combinations of agents with different (TP53 independent) targets, including kinase inhibitors and inhibitors of anti-apoptotic molecules but also immunomodulatory agents need to be further explored.

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



    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...

  20. Studying chromium biosorption using arabica coffee leaves

    Directory of Open Access Journals (Sweden)

    Luis Carlos Florez García


    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. New mixed aluminium–chromium diarsenate

    Directory of Open Access Journals (Sweden)

    Mohamad Alem Bouhassine


    Full Text Available Potassium chromium aluminium diarsenate, KCr1/4Al3/4As2O7, was prepared by solid-state reaction. The structure consists of (Cr1/4/Al3/4O6 octahedra and As2O7 diarsenate groups sharing corners to build up a three-dimensional anionic framework. The potassium cations are located in wide channels running along the c-axis direction. The crystal structure is isostructural with the triclinic AIMIIIX2O7 (AI = alkali metal; MIII = Al, Cr, Fe; X = As, P compounds. However, the MIII octahedrally coordinated site is 25% partially occupied by chromium and 75% by aluminium.

  2. Strategies for chromium bioremediation of tannery effluent. (United States)

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


    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

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

    Directory of Open Access Journals (Sweden)

    Villiard Éric


    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. Fluctuations in Precambrian atmospheric oxygenation recorded by chromium isotopes (United States)

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


    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.

  5. Chemical Variations on the p53 Reactivation Theme

    Directory of Open Access Journals (Sweden)

    Carlos J. A. Ribeiro


    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. 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:; 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)


    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

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


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


    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 ...

  8. Chromium allergy and dermatitis: prevalence and main findings

    DEFF Research Database (Denmark)

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


    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...... allergy, emphasizing that the investigation of chromium allergy is still far from complete. Our review article on chromium focuses on the allergen’s chemical properties, its potential exposure sources, and the allergen’s interaction with the skin, and also provides an overview of the regulations...

  9. Tumor suppressor p53 meets microRNAs



    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 expr...

  10. Chromium supplementation in patients with type 2 diabetes and high risk of type 2 diabetes: a meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Ismael San Mauro Martín

    Full Text Available Introduction: Chromium is an essential trace mineral for carbohydrate and lipid metabolism, which is currently prescribed to control diabetes mellitus. Results of previous systematic reviews and meta-analyses of chromium supplementation and metabolic profiles in diabetes have been inconsistent. Aim: The objective of this meta-analysis was to assess the effects on metabolic profiles and safety of chromium supplementation in type 2 diabetes mellitus and cholesterol. Methods: Literature searches in PubMed, Scopus and Web of Science were made by use of related terms-keywords and randomized clinical trials during the period of 2000-2014. Results: Thirteen trials fulfilled the inclusion criteria and were included in this systematic review. Total doses of Cr supplementation and brewer's yeast ranged from 42 to 1,000 µg/day, and duration of supplementation ranged from 30 to 120 days. The analysis indicated that there was a significant effect of chromium supplementation in diabetics on fasting plasma glucose with a weighted average effect size of -29.26 mg/dL, p = 0.01, CI 95% = -52.4 to -6.09; and on total cholesterol with a weighted average effect size of -6.7 mg/dL, p = 0.01, CI 95% = -11.88 to -1.53. Conclusions: The available evidence suggests favourable effects of chromium supplementation on glycaemic control in patients with diabetes. Chromium supplementation may additionally improve total cholesterol levels.

  11. Pharmacokinetic Modeling of Trivalent and Hexavalent Chromium Based on Ingestion and Inhalation of Soluble Chromium Compounds. (United States)


    be largely Cr(III) although some Cr(VI) exposure probably also occurs. Stainless-steel welders are exposed to nickel as well as to chromium compounds...welders are equivocal with respect to involvement of chromium, particularly since nickel in some chemical forms is an established lung carcinogen (Stern...microglobulin (Lindberg and Vesterberg, 1983), retinol-binding protein (Franchini and Mutti , 1988), B-glucuronidase ( Mutti et al., 1979), and kidney brush border

  12. Biological groundwater treatment for chromium removal at low hexavalent chromium concentrations. (United States)

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


    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.

  13. The electronic structure of antiferromagnetic chromium

    DEFF Research Database (Denmark)

    Skriver, Hans Lomholt


    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...

  14. A Kinetic Model of Chromium in a Flame

    Institute of Scientific and Technical Information of China (English)


    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

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

    Directory of Open Access Journals (Sweden)

    Pokusová Marcela


    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.

  16. 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


    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.

  17. 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. (United States)

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


    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.

  18. 77 FR 6627 - National Emission Standards for Hazardous Air Pollutant Emissions: Hard and Decorative Chromium... (United States)


    ... aluminum to provide resistance to corrosion. The chromium anodizing process is used to coat aircraft parts... Hazardous Air Pollutant Emissions: Hard and Decorative Chromium Electroplating and Chromium Anodizing Tanks... Pollutant Emissions: Hard and Decorative Chromium Electroplating and Chromium Anodizing Tanks; and...


    Directory of Open Access Journals (Sweden)

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


    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.

  20. Structural plasticity of methyllysine recognition by the tandem Tudor domain of 53BP1 (United States)

    Tong, Qiong; Cui, Gaofeng; Botuyan, Maria Victoria; Rothbart, Scott B.; Hayashi, Ryo; Musselman, Catherine A.; Singh, Namit; Appella, Ettore; Strahl, Brian D.; Mer, Georges; Kutateladze, Tatiana G.


    SUMMARY p53 is dynamically regulated through various posttranslational modifications (PTMs), which differentially modulate its function and stability. The dimethylated marks p53K370me2 and p53K382me2 are associated with p53 activation or stabilization and both are recognized by the tandem Tudor domain (TTD) of 53BP1, a p53 co-factor. Here we detail the molecular mechanisms for the recognition of p53K370me2 and p53K382me2 by 53BP1. The solution structures of TTD in complex with the p53K370me2 and p53K382me2 peptides show a remarkable plasticity of 53BP1 in accommodating these diverse dimethyllysine-containing sequences. We demonstrate that dimeric TTDs are capable of interacting with the two PTMs on a single p53K370me2K382me2 peptide, greatly strengthening the 53BP1-p53 interaction. Analysis of binding affinities of TTD toward methylated p53 and histones reveals strong preference of 53BP1 for p53K382me2, H4K20me2, and H3K36me2 and suggests a possible role of multivalent contacts of 53BP1 in p53 targeting to and accumulation at the sites of DNA damage. PMID:25579814

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

    Energy Technology Data Exchange (ETDEWEB)

    Kotsedi, L., E-mail: [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)


    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%.

  2. Production of basic chromium sulfate by using recovered chromium from ashes of thermally treated leather. (United States)

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


    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.

  3. Interactions of chromium with microorganisms and plants. (United States)

    Cervantes, C; Campos-García, J; Devars, S; Gutiérrez-Corona, F; Loza-Tavera, H; Torres-Guzmán, J C; Moreno-Sánchez, R


    Chromium is a highly toxic non-essential metal for microorganisms and plants. Due to its widespread industrial use, chromium (Cr) has become a serious pollutant in diverse environmental settings. The hexavalent form of the metal, Cr(VI), is considered a more toxic species than the relatively innocuous and less mobile Cr(III) form. The presence of Cr in the environment has selected microbial and plant variants able to tolerate high levels of Cr compounds. The diverse Cr-resistance mechanisms displayed by microorganisms, and probably by plants, include biosorption, diminished accumulation, precipitation, reduction of Cr(VI) to Cr(III), and chromate efflux. Some of these systems have been proposed as potential biotechnological tools for the bioremediation of Cr pollution. In this review we summarize the interactions of bacteria, algae, fungi and plants with Cr and its compounds.

  4. Chromium isotope composition of reducing and anoxic sediments from the Peru Margin and Cariaco Basin (United States)

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


    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

  5. 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


    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.

  6. Speciation and recovery of chromium from chromite ore processing residues. (United States)

    Sreeram, K J; Ramasami, T


    The processing of chromite ore is associated with the generation of large quantities of solid wastes containing chromium, which have been disposed of as landfill for many years. The mobilization and operational speciation of chromium contained in soils contaminated with metal salts are important in terms of the environment. Several methods have been employed for the extraction and recovery of solid wastes. Chromium contained in contaminated soils and solid wastes can be categorized as exchangeable, oxidizable, carbonate-bound, reducible and residual. The results from this study indicate a need for efficient leaching methodologies in chromite ore processing plants to decrease the non-detrital fractions of chromium in the residue. Aggressive methodologies are required to recover chromium from the detrital fractions. The potential benefits of employing sodium peroxide for the complete recovery of chromium from chromite residue have been demonstrated, and the need to ensure the safety of the process has been emphasized.

  7. Chromium Toxicity: Reductive Enzymes in Humans. (United States)


    internal organs (e.g. lungs, liver, kidneys) [24,27,64], pulmonary fibrosis and chronic bronchitis [2], skin ulcers and allergic dermatitis [2], and...cross the skin [2] and are readily transported across cell membranes [18] via an anion carrier [6]. Cr compounds are also mutagenic [67], and the bulk of...reduced nicotinamide adenine dinucleotide phosphate-cytochrome P450 oxidoreductase- dependent chromium(VI) reduction. Analyst 120:935-938. 42. Miura, A

  8. 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.

  9. Elementary surface processes during reactive magnetron sputtering of chromium

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  10. 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)


    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.

  11. 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.

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


    Palmer, C.D.; Wittbrodt, P R


    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...

  13. 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


    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.

  14. 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.

  15. Tumor suppressor p53 meets microRNAs

    Institute of Scientific and Technical Information of China (English)

    Zhaohui Feng; Cen Zhang; Rui Wu; Wenwei Hu


    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.

  16. 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)


    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.

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

    Institute of Scientific and Technical Information of China (English)

    GUKa-fi; HUAMeng; Yi-min


    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.



  19. Chromium recycling of tannery waste through microbial fermentation. (United States)

    Katsifas, E A; Giannoutsou, E; Lambraki, M; Barla, M; Karagouni, A D


    An Aspergillus carbonarius isolate, selected from an established microbial culture collection, was used to study the biodegradation of chromium shavings in solid-state fermentation experiments. Approximately 97% liquefaction of the tannery waste was achieved and the liquid obtained from long-term experiments was used to recover chromium. The resulting alkaline chromium sulfate solution was useful in tanning procedures. A proteinaceous liquid was also obtained which has potential applications as a fertilizer or animal feed additive and has several other industrial uses. The A. carbonarius strain proved to be a very useful tool in tannery waste-treatment processes and chromium recovery in the tanning industries.

  20. Influence of Chelating Agents on Chromium Fate in Sediment

    Institute of Scientific and Technical Information of China (English)



    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.

  1. Cost-Efficient and Sustainable Deployment of Renewable Energy Sources towards the 20% Target by 2020, and beyond. D5.3. Key recommendations from the RES4LESS roadmap

    Energy Technology Data Exchange (ETDEWEB)

    Dalla Longa, F. [ECN Policy Studies, Amsterdam (Netherlands); Raimundo, C. [IT Power, Bristol, Avon (United Kingdom)


    In its Directive 2009/28/EC the European Commission (EC) set an ambitious 20% target on the final consumption of energy from renewable sources (RES) in 2020 (European Commission, 2009). This EU-level target is divided into different domestic targets for each single Member State (MS). The MS-level targets do not always reflect the domestic RES potentials, creating a situation where certain MSs will have to deploy very expensive technologies in order to meet their target, while other countries are expected to reach their target at lower costs and even produce a RES surplus. In order to promote a more balanced distribution of costs, the Directive allows MSs to establish cooperation mechanisms. Three types of cooperation mechanisms are defined: a MS could buy the RES-credits associated with the surplus potential of other MSs via statistical transfers, could finance additional RES deployment in other MSs by engaging in joint projects, or could share (part of) its RES potential with other MSs by establishing joint support schemes.

  2. p53 gene therapy using RNA interference. (United States)

    Berindan-Neagoe, I; Balacescu, O; Burz, C; Braicu, C; Balacescu, L; Tudoran, O; Cristea, V; Irimie, A


    p53 gene, discovered almost 35 years ago, keeps the main role in cell cycle control, apoptosis pathways and transcription. p53 gene is found mutated in more than 50% of all human cancers in different locations. Many structures from viral to non viral were designed to incorporate and deliver in appropriate conditions forms of p53 gene or its transcripts, systemically to target tumor cells and to eliminate them through apoptosis or to restore the normal tumor suppressor gene role. Each delivery system presents advantages and low performance in relation to immune system recognition and acceptance. One of the major discoveries in the last years, silencing of RNA, represents a powerful tool for inhibiting post transcriptional control of gene expression. According to several studies, the RNA silencing technology for p53 transcripts together with other carriers or transporters at nano level can be used for creating new therapeutic models. RNA interference for p53 uses different double-stranded (ds) molecules like short interfering (si) RNA and, despite the difficulty of introducing them into mammalian cells due to immune system response, it can be exploited in cancer therapy.

  3. Induction of p53-Specific Immunity by a p53 Synthetic Long Peptide Vaccine in Patients Treated for Metastatic Colorectal Cancer

    NARCIS (Netherlands)

    Speetjens, Frank M.; Kuppen, PeterJ. K.; Welters, Marij. J. P.; Essahsah, Farah; van den Brink, Anne Marie E. G. Voet; Lantrua, M. Graziella Kallenberg; Valentijn, A. Rob P. M.; Oostendorp, Jaap; Fathers, Lorraine M.; Nijman, Hans W.; Drijfhout, Jan W.; van de Velde, Cornelis J. H.; Melief, Cornelis J. M.; van der Burg, Sjoerd H.


    Purpose: The tumor-associated self-antigen p53 is commonly overexpressed in cancer, including colorectal cancer, and can serve as a target for immunotherapy. The safety and immunogenicity of a p53 synthetic long peptide (p53-SLP) vaccine were investigated in patients treated for metastatic colorecta

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

    Directory of Open Access Journals (Sweden)

    Valverde, J. L.


    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. Recognition of Local DNA Structures by p53 Protein. (United States)

    Brázda, Václav; Coufal, Jan


    p53 plays critical roles in regulating cell cycle, apoptosis, senescence and metabolism and is commonly mutated in human cancer. These roles are achieved by interaction with other proteins, but particularly by interaction with DNA. As a transcription factor, p53 is well known to bind consensus target sequences in linear B-DNA. Recent findings indicate that p53 binds with higher affinity to target sequences that form cruciform DNA structure. Moreover, p53 binds very tightly to non-B DNA structures and local DNA structures are increasingly recognized to influence the activity of wild-type and mutant p53. Apart from cruciform structures, p53 binds to quadruplex DNA, triplex DNA, DNA loops, bulged DNA and hemicatenane DNA. In this review, we describe local DNA structures and summarize information about interactions of p53 with these structural DNA motifs. These recent data provide important insights into the complexity of the p53 pathway and the functional consequences of wild-type and mutant p53 activation in normal and tumor cells.

  6. 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


    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

  7. Fluctuations in Precambrian atmospheric oxygenation recorded by chromium isotopes. (United States)

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


    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

  8. P53 tumor suppression network in cancer epigenetics. (United States)

    Mishra, Alok; Brat, Daniel J; Verma, Mukesh


    The tumor suppressor p53 is one of the most complex and widely studied genes in cancer biology. In spite of the vast on literature the transcriptional regulation of p53, aspects of its especially epigenetic regulation are not completely understood. This chapter presents a concise overview of p53-related epigenetic events involved in oncogenesis and tumor suppression. We limit the scope to epigenetic modifications of the p53 promoter per se as well as its well-established downstream targets. The indirect role of p53 affecting the epigenetic machinery of cancer cells via specific proteins and transcription factors is discussed. Current concepts of p53-related cancer epigenetics offer myriad avenues for cancer therapies. Challenges in the field are also discussed.

  9. Development of analytical procedures for determination of total chromium by quadrupole ICP-MS and high-resolution ICP-MS, and hexavalent chromium by HPLC-ICP-MS, in different materials used in the automotive industry. (United States)

    Séby, F; Gagean, M; Garraud, H; Castetbon, A; Donard, O F X


    A European directive was recently adopted limiting the use of hazardous substances such as Pb, Hg, Cd, and Cr(VI) in vehicle manufacturing. From July 2003 a maximum of 2 g Cr(VI) will be authorised per vehicle in corrosion-preventing coatings of key components. As no standardised procedures are available to check if produced vehicles are in agreement with this directive, the objective of this work was to develop analytical procedures for total chromium and Cr(VI) determination in these materials. The first step of this study was to optimise digestion procedures for total chromium determination in plastic and metallic materials by inductively coupled plasma mass spectrometry (ICP-MS). High resolution (HR) ICP-MS was used to examine the influence of polyatomic interferences on the detection of the (52)Cr(+) and (53)Cr(+) isotopes. If there was strong interference with m/ z 52 for plastic materials, it was possible to use quadrupole ICP-MS for m/ z 53 if digestions were performed with HNO(3)+H(2)O(2). This mixture was also necessary for digestion of chromium from metallic materials. Extraction procedures in alkaline medium (NH(4)(+)/NH(3) buffer solution at pH 8.9) assisted by sonication were developed for determining Cr(VI) in four different corrosion-preventing coatings by HPLC-ICP-MS. After optimisation and validation with the only solid reference material certified for its Cr(VI) content (BCR 545; welding dusts), the efficiency of this extraction procedure for screw coatings was compared with that described in the EN ISO 3613 standard generally used in routine laboratories. For coatings comprising zinc and aluminium passivated in depth with chromium oxides the extraction procedure developed herein enabled determination of higher Cr(VI) concentrations. This was also observed for the screw covered with a chromium passivant layer on zinc-nickel. For coating comprising a chromium passivant layer on alkaline zinc the standardized extraction procedure was more efficient

  10. Diffusion of hexavalent chromium in chromium-containing slag as affected by microbial detoxification. (United States)

    Wang, Yunyan; Yang, Zhihui; Chai, Liyuan; Zhao, Kun


    An electrochemical method was used to determine the diffusion coefficient of chromium(VI) in chromium-containing slag. A slag plate was prepared from the original slag or the detoxified slag by Achromobacter sp. CH-1. The results revealed that the apparent diffusion coefficient of Cr(VI) was 4.4 x 10(-9)m(2)s(-1) in original slag and 2.62 x 10(-8)m(2)s(-1) in detoxified slag. The results implied that detoxification of chromium-containing slag by Achromobacter sp. CH-1 could enhance Cr(VI) release. Meanwhile, the results of laboratory experiment showed that the residual total Cr(VI) in slag decreased from an initial value of 6.8 mg g(-1) to 0.338 mg g(-1) at the end of the detoxification process. The Cr(VI) released from slag was also reduced by Achromobacter sp. CH-1 strain since water soluble Cr(VI) in the leachate was not detected after 4 days. Therefore, Achromobacter sp. CH-1 has potential application for the bio-detoxification of chromium-containing slag.

  11. Safety, absorption, and antioxidant effects of chromium histidine (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...

  12. Mechanisms of bacterial resistance to chromium compounds. (United States)

    Ramírez-Díaz, Martha I; Díaz-Pérez, César; Vargas, Eréndira; Riveros-Rosas, Héctor; Campos-García, Jesús; Cervantes, Carlos


    Chromium is a non-essential and well-known toxic metal for microorganisms and plants. The widespread industrial use of this heavy metal has caused it to be considered as a serious environmental pollutant. Chromium exists in nature as two main species, the trivalent form, Cr(III), which is relatively innocuous, and the hexavalent form, Cr(VI), considered a more toxic species. At the intracellular level, however, Cr(III) seems to be responsible for most toxic effects of chromium. Cr(VI) is usually present as the oxyanion chromate. Inhibition of sulfate membrane transport and oxidative damage to biomolecules are associated with the toxic effects of chromate in bacteria. Several bacterial mechanisms of resistance to chromate have been reported. The best characterized mechanisms comprise efflux of chromate ions from the cell cytoplasm and reduction of Cr(VI) to Cr(III). Chromate efflux by the ChrA transporter has been established in Pseudomonas aeruginosa and Cupriavidus metallidurans (formerly Alcaligenes eutrophus) and consists of an energy-dependent process driven by the membrane potential. The CHR protein family, which includes putative ChrA orthologs, currently contains about 135 sequences from all three domains of life. Chromate reduction is carried out by chromate reductases from diverse bacterial species generating Cr(III) that may be detoxified by other mechanisms. Most characterized enzymes belong to the widespread NAD(P)H-dependent flavoprotein family of reductases. Several examples of bacterial systems protecting from the oxidative stress caused by chromate have been described. Other mechanisms of bacterial resistance to chromate involve the expression of components of the machinery for repair of DNA damage, and systems related to the homeostasis of iron and sulfur.

  13. Observational Approach to Chromium Site Remediation - 13266

    Energy Technology Data Exchange (ETDEWEB)

    Scott Myers, R. [Washington Closure Hanford, 2620 Fermi, Richland, Washington 99354 (United States)


    Production reactors at the U.S. Department of Energy's (DOE) Hanford Site in Richland, Washington, required massive quantities of water for reactor cooling and material processing. To reduce corrosion and the build-up of scale in pipelines and cooling systems, sodium dichromate was added to the water feedstock. Spills and other releases at the makeup facilities, as well as leaks from miles of pipelines, have led to numerous areas with chromium-contaminated soil and groundwater, threatening fish populations in the nearby Columbia River. Pump-and-treat systems have been installed to remove chromium from the groundwater, but significant contamination remain in the soil column and poses a continuing threat to groundwater and the Columbia River. Washington Closure Hanford, DOE, and regulators are working on a team approach that implements the observational approach, a strategy for effectively dealing with the uncertainties inherent in subsurface conditions. Remediation of large, complex waste sites at a federal facility is a daunting effort. It is particularly difficult to perform the work in an environment of rapid response to changing field and contamination conditions. The observational approach, developed by geotechnical engineers to accommodate the inherent uncertainties in subsurface conditions, is a powerful and appropriate method for site remediation. It offers a structured means of quickly moving into full remediation and responding to the variations and changing conditions inherent in waste site cleanups. A number of significant factors, however, complicate the application of the observational approach for chromium site remediation. Conceptual models of contamination and site conditions are difficult to establish and get consensus on. Mid-stream revisions to the design of large excavations are time-consuming and costly. And regulatory constraints and contract performance incentives can be impediments to the flexible responses required under the

  14. Atom Lithography with a Chromium Atomic Beam

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wen-Tao; LI Tong-Bao


    @@ Direct write atom lithography is a new technique in which resonant light is used to pattern an atomic beam and the nanostructures are formed when the atoms deposit on the substrate. We design an experiment setup to fabricate chromium nanolines by depositing an atomic beam of 52 Cr through an off-resonant laser standing wave with the wavelength of 425.55 nm onto a silicon substrate. The resulting nanolines exhibit a period of 215 ± 3 nm with height of 1 nm.

  15. The fate of chromium during tropical weathering

    DEFF Research Database (Denmark)

    Berger, Alfons; Frei, Robert


    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......, in the soil, relative to bedrock and underlying saprolite, are the characteristic features pertinent to laterites. The enrichment of Fe in topsoil horizon can be correlated with enrichment of P, and the redox sensitive elements Mn and Cr, and indicates redistribution of these elements related to oxidation...

  16. Bioleaching of chromium from tannery sludge by indigenous Acidithiobacillus thiooxidans. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Rolletschek Alexandra


    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.

  18. Full p53 transcriptional activation potential is dispensable for tumor suppression in diverse lineages. (United States)

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


    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.

  19. Positive effect of Mdm2 on p53 expression explains excitability of p53 in response to DNA damage. (United States)

    Eliaš, Ján


    Most of the existing biological models consider Mdm2 as a dominant negative regulator of p53 appearing in several negative feedback loops. However, in addition to targeting p53 for degradation, Mdm2 in tight cooperation with MdmX can control expression levels of p53 through enhanced induction of p53 synthesis in response to DNA damage. Whilst ATM-dependent phosphorylation of p53 is not observed to be important in this enhanced synthesis, ATM-dependent phosphorylation of Mdm2 (as well as MdmX) is essential for its dual role, which is accompanied with widely oscillating p53. In the light of these new observations we formulate a novel molecular mechanism which, in silico, is capable of triggering p53 oscillations. The mechanism that is based on Mdm2's dual regulation of p53 can provide mechanistic insights into an excitability of the p53 network, thus it contributes to understanding of variability of p53 dynamics in response to single and double strand breaks.

  20. HDAC6 deacetylates p53 at lysines 381/382 and differentially coordinates p53-induced apoptosis. (United States)

    Ryu, Hyun-Wook; Shin, Dong-Hee; Lee, Dong Hoon; Choi, Junjeong; Han, Gyoonhee; Lee, Kang Young; Kwon, So Hee


    HDAC6-selective inhibitors represent promising new cancer therapeutic agents, but their precise mechanisms of action are not well understood. In particular, p53's role in HDAC6 inhibitor-induced effects has not been fully elucidated. In this study, we show that an HDAC6-selective inhibitor, A452, increased wild-type p53 levels by destabilizing MDM2, but decreased mutant p53 by inducing MDM2 and inhibiting Hsp90-mutant p53 complex formation. Interestingly, HDAC6 levels inversely correlated with p53 acetylation at lysines 381/382 associated with p53 functional activation. A452 blocked HDAC6 nuclear localization, resulting in increased levels of acetylated p53 at Lys381/382. HDAC6 bound to the C-terminal region of p53 via its deacetylase domain. A452 disrupted the HDAC6-Hsp90 chaperone machinery via Hsp90 acetylation and degradation. Furthermore, it chemosensitized cancer cells to the Hsp90 inhibitor 17-AAG. Overall, silencing of HDAC6 showed similar effects. These findings suggest that the anticancer action of HDAC6 inhibitors requires p53 and Hsp90 and targeting of HDAC6 may represent a new therapeutic strategy for cancers regardless of p53's mutation status.

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


    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.

  2. The Theory for the Mechanism of Chromium Plating: The Theory for the Physical Characteristics of Chromium Plate (United States)


    deposits arc pro- duced as the coll potential is successively raised. The sulfato ion "hus has an extremely important effect in the chromium plating...and sulfato iDU in the bath wore then used in an attempt to obtain more satisfactory hexagonal chromium deposits. The data obtained are summarUod

  3. Ligand dependent restoration of human TLR3 signaling and death in p53 mutant cells. (United States)

    Menendez, Daniel; Lowe, Julie M; Snipe, Joyce; Resnick, Michael A


    Diversity within the p53 transcriptional network can arise from a matrix of changes that include target response element sequences and p53 expression level variations. We previously found that wild type p53 (WT p53) can regulate expression of most innate immune-related Toll-like-receptor genes (TLRs) in human cells, thereby affecting immune responses. Since many tumor-associated p53 mutants exhibit change-of-spectrum transactivation from various p53 targets, we examined the ability of twenty-five p53 mutants to activate endogenous expression of the TLR gene family in p53 null human cancer cell lines following transfection with p53 mutant expression vectors. While many mutants retained the ability to drive TLR expression at WT levels, others exhibited null, limited, or change-of-spectrum transactivation of TLR genes. Using TLR3 signaling as a model, we show that some cancer-associated p53 mutants amplify cytokine, chemokine and apoptotic responses after stimulation by the cognate ligand poly(I:C). Furthermore, restoration of WT p53 activity for loss-of-function p53 mutants by the p53 reactivating drug RITA restored p53 regulation of TLR3 gene expression and enhanced DNA damage-induced apoptosis via TLR3 signaling. Overall, our findings have many implications for understanding the impact of WT and mutant p53 in immunological responses and cancer therapy.

  4. Negative auto-regulators trap p53 in their web. (United States)

    Zhou, Xiang; Cao, Bo; Lu, Hua


    The transcriptional factor p53 activates the expression of a myriad of target genes involving a complicated signalling network, resulting in various cellular outcomes, such as growth arrest, senescence, apoptosis, and metabolic changes, and leading to consequent suppression of tumour growth and progression. Because of the profoundly adverse effect of p53 on growth and proliferation of cancer cells, several feedback mechanisms have been employed by the cells to constrain p53 activity. Two major antagonists MDM2 and MDMX (the long forms) are transcriptionally induced by p53, but in return block p53 activity, forming a negative feedback circuit and rendering chemoresistance of several cancer cells. However, they are not alone, as cancer cells also employ other proteins encoded by p53 target genes to inhibit p53 activity at transcriptional, translational, and posttranslational levels. This essay is thus composed to review a recent progress in understanding the mechanisms for how cancer cells hijack the p53 autoregulation by these proteins for their growth advantage and to discuss the clinical implications of these autoregulatory loops.

  5. Dissolution of chromium in sulfuric acid

    Directory of Open Access Journals (Sweden)

    J. P. POPIC


    Full Text Available By combining electrochemical corrosion rate measurements and spectrophotometric analysis of the electrolyte it was shown that at room temperature chromium dissolves in deaerated 0.1 M Na2SO4 + H2SO4 (pH 1 solution as Cr(II and Cr(III ions in he ratio Cr(II : Cr(III @ 7 : 1. This process was stable over 4 h without any detectable change. The total corrosion rate of chromium calculated from the analytical data is about 12 times higher, than that determined electrochemically by cathodic Tafel line extrapolation to the corrosion potential. This finding was confirmed by applying the weight-loss method for the determination of the corrosion rate. This enormous difference between these experimentally determined corrosion rates can be explained by the rather fast, “anomalous” dissolution process proposed by Kolotyrkin and coworkers (chemical reaction of Cr with H2O molecules occurring simultaneously with the electrochemical corrosion process.

  6. Psychoneuroimmunology and natural killer cells: the chromium release whole blood assay. (United States)

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


    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.

  7. Electrochemical modification of chromium surfaces using 4-nitro- and4-fluorobenzenediazonium salts

    DEFF Research Database (Denmark)

    Hinge, Mogens; Cecatto, Marcel; Kingshott, Peter;


    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......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...

  8. 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


    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

  9. Small-Molecule NSC59984 Restores p53 Pathway Signaling and Antitumor Effects against Colorectal Cancer via p73 Activation and Degradation of Mutant p53. (United States)

    Zhang, Shengliang; Zhou, Lanlan; Hong, Bo; van den Heuvel, A Pieter J; Prabhu, Varun V; Warfel, Noel A; Kline, Christina Leah B; Dicker, David T; Kopelovich, Levy; El-Deiry, Wafik S


    The tumor-suppressor p53 prevents cancer development via initiating cell-cycle arrest, cell death, repair, or antiangiogenesis processes. Over 50% of human cancers harbor cancer-causing mutant p53. p53 mutations not only abrogate its tumor-suppressor function, but also endow mutant p53 with a gain of function (GOF), creating a proto-oncogene that contributes to tumorigenesis, tumor progression, and chemo- or radiotherapy resistance. Thus, targeting mutant p53 to restore a wild-type p53 signaling pathway provides an attractive strategy for cancer therapy. We demonstrate that small-molecule NSC59984 not only restores wild-type p53 signaling, but also depletes mutant p53 GOF. NSC59984 induces mutant p53 protein degradation via MDM2 and the ubiquitin-proteasome pathway. NSC59984 restores wild-type p53 signaling via p73 activation, specifically in mutant p53-expressing colorectal cancer cells. At therapeutic doses, NSC59984 induces p73-dependent cell death in cancer cells with minimal genotoxicity and without evident toxicity toward normal cells. NSC59984 synergizes with CPT11 to induce cell death in mutant p53-expressing colorectal cancer cells and inhibits mutant p53-associated colon tumor xenograft growth in a p73-dependent manner in vivo. We hypothesize that specific targeting of mutant p53 may be essential for anticancer strategies that involve the stimulation of p73 in order to efficiently restore tumor suppression. Taken together, our data identify NSC59984 as a promising lead compound for anticancer therapy that acts by targeting GOF-mutant p53 and stimulates p73 to restore the p53 pathway signaling.

  10. The Mechanism of p53 Rescue by SUSP4. (United States)

    Kim, Do-Hyoung; Lee, Chewook; Lee, Si-Hyung; Kim, Kyung-Tae; Han, Joan J; Cha, Eun-Ji; Lim, Ji-Eun; Cho, Ye-Jin; Hong, Seung-Hee; Han, Kyou-Hoon


    p53 is an important tumor-suppressor protein deactivation of which by mdm2 results in cancers. A SUMO-specific protease 4 (SUSP4) was shown to rescue p53 from mdm2-mediated deactivation, but the mechanism is unknown. The discovery by NMR spectroscopy of a "p53 rescue motif" in SUSP4 that disrupts p53-mdm2 binding is presented. This 29-residue motif is pre-populated with two transient helices connected by a hydrophobic linker. The helix at the C-terminus binds to the well-known p53-binding pocket in mdm2 whereas the N-terminal helix serves as an affinity enhancer. The hydrophobic linker binds to a previously unidentified hydrophobic crevice in mdm2. Overall, SUSP4 appears to use two synergizing modules, the p53 rescue motif described here and a globular-structured SUMO-binding catalytic domain, to stabilize p53. A p53 rescue motif peptide exhibits an anti-tumor activity in cancer cell lines expressing wild-type p53. A pre-structures motif in the intrinsically disordered proteins is thus important for target recognition.

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

    Energy Technology Data Exchange (ETDEWEB)


    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.

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

  13. Magnetite nanoparticle (NP) uptake by wheat plants and its effect on cadmium and chromium toxicological behavior

    Energy Technology Data Exchange (ETDEWEB)

    López-Luna, J., E-mail: [Instituto de Estudios Ambientales, Universidad de la Sierra Juárez, Ixtlán de Juárez 68725, Oaxaca (Mexico); Silva-Silva, M.J. [Instituto de Estudios Ambientales, Universidad de la Sierra Juárez, Ixtlán de Juárez 68725, Oaxaca (Mexico); Martinez-Vargas, S. [Facultad de Ingeniería, Universidad Autónoma del Carmen, Ciudad del Carmen 24115, Campeche (Mexico); Mijangos-Ricardez, O.F. [Instituto de Estudios Ambientales, Universidad de la Sierra Juárez, Ixtlán de Juárez 68725, Oaxaca (Mexico); González-Chávez, M.C. [Colegio de Postgraduados en Ciencias Agrícolas, Carr. México–Texcoco km 36.5, Montecillo 56230, Estado de México (Mexico); Solís-Domínguez, F.A. [Facultad de Ingeniería, Universidad Autónoma de Baja California, Mexicali 21280, Baja California Norte (Mexico); Cuevas-Díaz, M.C. [Facultad de Ciencias Químicas, Universidad Veracruzana, Coatzacoalcos 96535, Veracruz (Mexico)


    The aim of this work was to assess the uptake of citrate-coated magnetite nanoparticles (NPs) by wheat plants and its effect on the bioaccumulation and toxicity of individual and joint Cd{sup 2+} and Cr{sup 6+} levels. Seven-day assays were conducted using quartz sand as the plant growth substrate. The endpoints measured were seed germination, root and shoot lengths, and heavy metal accumulation. Magnetite exhibited very low toxicity, regardless of the wheat seedling NP uptake and distribution into roots and shoots. The seed germination and shoot length were not sensitive enough, while the root length was a more sensitive toxicity endpoint. The root length of wheat seedlings exposed to individual metals decreased by 50% at 2.67 mg Cd{sup 2+} kg{sup −1} and 5.53 mg Cr{sup 6+} kg{sup −1}. However, when magnetite NPs (1000 mg kg{sup −1}) were added, the root length of the plants increased by 25 and 50%. Cd{sup 2+} and Cr{sup 6+} showed similar and noninteractive joint action, but strongly impaired the wheat seedlings. In contrast, an interactive infra-additive or antagonistic effect was observed upon adding magnetite NPs. Thus, cadmium and chromium accumulation in vegetable tissues was considerately diminished and the toxicity alleviated. - Highlights: • We assessed the effect of nanomagnetite on heavy metal toxicity in wheat plants. • Citrate-coated magnetite nanoparticles (NPs) exerted very low toxicity to plants. • Cadmium was more toxic than chromium and toxicity was mitigated by magnetite NPs. • Cadmium and chromium had a similar and noninteractive joint action on plants. • Metals showed an interactive infra-additive joint effect by adding magnetite NPs.

  14. Alpha-emitting isotopes and chromium in a coastal California aquifer (United States)

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


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, H.K.


    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 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.

  16. Chromium Content in the Human Hip Joint Tissues

    Institute of Scientific and Technical Information of China (English)

    Barbara Brodziak-Dopiera; Jerzy Kwapuliski; Krzysztof Sobczyk; Danuta Wiechua


    Objective Chromium has many important functions in the human body. For the osseous tissue, its role has not been clearly defined. This study was aimed at determining chromium content in hip joint tissues. Methods A total of 91 hip joint samples were taken in this study, including 66 from females and 25 from males. The sample tissues were separated according to their anatomical parts. The chromium content was determined by the AAS method. The statistical analysis was performed with U Mann-Whitney's non-parametric test, P≤0.05. Results The overall chromium content in tissues of the hip joint in the study subjects was as follows:5.73 µg/g in the articular cartilage, 5.33 µg/g in the cortical bone, 17.86 µg/g in the cancellous bone, 5.95 µg/g in the fragment of the cancellous bone from the intertrochanteric region, and 1.28 µg/g in the joint capsule. The chromium contents were observed in 2 group patients, it was 7.04 µg/g in people with osteoarthritis and 12.59 µg/g in people with fractures. Conclusion The observed chromium content was highest in the cancellous bone and the lowest in the joint capsule. Chromium content was significantly different between the people with hip joint osteoarthritis and the people with femoral neck fractures.

  17. Mode of occurrence of chromium in four US coals (United States)

    Huggins, Frank E.; Shah, N.; Huffman, G.P.; Kolker, A.; Crowley, S.; Palmer, C.A.; Finkelman, R.B.


    The mode of occurrence of chromium in three US bituminous coals and one US subbituminous has been examined using both X-ray absorption fine structure (XAFS) spectroscopy and a selective leaching protocol supplemented by scanning electron microscopy (SEM) and electron microprobe measurements. A synthesis of results from both methods indicates that chromium occurs principally in two forms in the bituminous coals: the major occurrence of chromium is associated with the macerals and is not readily leached by any reagent, whereas a second, lesser occurrence, which is leachable in hydrofluoric acid (HF), is associated with the clay mineral, illite. The former occurrence is believed to be a small particle oxyhydroxide phase (CrO(OH)). One coal also contained a small fraction (<5%) of the chromium in the form of a chromian magnetite, and the leaching protocol indicated the possibility of a similar small fraction of chromium in sulfide form in all three coals. There was little agreement between the two techniques on the mode of occurrence of chromium in the subbituminous coal; however, only a limited number of subbituminous coals have been analyzed by either technique. The chromium in all four coals was trivalent as no evidence was found for the Cr6+ oxidation state in any coal.

  18. Removal of chromium from tannery effluents by adsorption. (United States)

    Fadali, O A; Magdy, Y H; Daifullah, A A M; Ebrahiem, E E; Nassar, M M


    Tannery effluent is characterized not only by heavy loads but also with toxic heavy metals especially chromium ions. Chromium is considered an important source of contamination due to large volume of exhaust liquid discharged and solid sludge produced. Details on adsorption studies were carried out using synthetic chromium salts (chromium chloride) as adsorbate, and cement kiln dust (a waste from white cement industry) as adsorbent. Equilibrium isotherms have been determined for the adsorption of chromium ions on cement kiln dust. Kinetic study provided that the adsorption process is diffusion controlled. The experimental results have been fitted using Freundlich, Langmuir, and Redlich Peterson isotherms. The maximum adsorption capacity of cement kiln dust was found to be 33 mg/g. Industrial tannery effluent (22-mg/L chromium and COD 952 mg/L) was also treated by cement dust. The treated effluent (using 20 g cement dust per 1 L) contains only 0.6 mg/L chromium and COD 200 mg/L.

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

    Institute of Scientific and Technical Information of China (English)


    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.

  20. Stabilization of chromium salt in ordinary portland cement

    Indian Academy of Sciences (India)

    Damir Barbir; Pero Dabić; Petar Krolo


    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.

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

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


    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.

  2. 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


    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.

  3. p53 isoform Δ113p53/Δ133p53 promotes DNA double-strand break repair to protect cell from death and senescence in response to DNA damage. (United States)

    Gong, Lu; Gong, Hongjian; Pan, Xiao; Chang, Changqing; Ou, Zhao; Ye, Shengfan; Yin, Le; Yang, Lina; Tao, Ting; Zhang, Zhenhai; Liu, Cong; Lane, David P; Peng, Jinrong; Chen, Jun


    The inhibitory role of p53 in DNA double-strand break (DSB) repair seems contradictory to its tumor-suppressing property. The p53 isoform Δ113p53/Δ133p53 is a p53 target gene that antagonizes p53 apoptotic activity. However, information on its functions in DNA damage repair is lacking. Here we report that Δ113p53 expression is strongly induced by γ-irradiation, but not by UV-irradiation or heat shock treatment. Strikingly, Δ113p53 promotes DNA DSB repair pathways, including homologous recombination, non-homologous end joining and single-strand annealing. To study the biological significance of Δ113p53 in promoting DNA DSB repair, we generated a zebrafish Δ113p53(M/M) mutant via the transcription activator-like effector nuclease technique and found that the mutant is more sensitive to γ-irradiation. The human ortholog, Δ133p53, is also only induced by γ-irradiation and functions to promote DNA DSB repair. Δ133p53-knockdown cells were arrested at the G2 phase at the later stage in response to γ-irradiation due to a high level of unrepaired DNA DSBs, which finally led to cell senescence. Furthermore, Δ113p53/Δ133p53 promotes DNA DSB repair via upregulating the transcription of repair genes rad51, lig4 and rad52 by binding to a novel type of p53-responsive element in their promoters. Our results demonstrate that Δ113p53/Δ133p53 is an evolutionally conserved pro-survival factor for DNA damage stress by preventing apoptosis and promoting DNA DSB repair to inhibit cell senescence. Our data also suggest that the induction of Δ133p53 expression in normal cells or tissues provides an important tolerance marker for cancer patients to radiotherapy.

  4. p53 prevents neurodegeneration by regulating synaptic genes. (United States)

    Merlo, Paola; Frost, Bess; Peng, Shouyong; Yang, Yawei J; Park, Peter J; Feany, Mel


    DNA damage has been implicated in neurodegenerative disorders, including Alzheimer's disease and other tauopathies, but the consequences of genotoxic stress to postmitotic neurons are poorly understood. Here we demonstrate that p53, a key mediator of the DNA damage response, plays a neuroprotective role in a Drosophila model of tauopathy. Further, through a whole-genome ChIP-chip analysis, we identify genes controlled by p53 in postmitotic neurons. We genetically validate a specific pathway, synaptic function, in p53-mediated neuroprotection. We then demonstrate that the control of synaptic genes by p53 is conserved in mammals. Collectively, our results implicate synaptic function as a central target in p53-dependent protection from neurodegeneration.

  5. Spectroscopic analysis of chromium bioremediation products (United States)

    Varadharajan, C.; Nico, P. S.; Yang, L.; Marcus, M. A.; Steefel, C.; Larsen, J. T.; Beller, H. R.; Brodie, E. L.


    Remediation of chromium contamination frequently involves reducing the toxic and soluble hexavalent form, Cr(VI), to the relatively harmless and mostly immobile trivalent state, Cr(III). The objective of this study is to identify the biogeochemical reactions that control in situ chromium reduction in the presence of different dominant electron acceptors, i.e., NO3-, Fe(III), and SO42-. It was hypothesized that indirect, abiotic reduction of Cr(VI) by reduced metabolic products [Fe(II) and sulfides] would dominate over direct enzymatic reduction by denitrifying, iron-reducing, or sulfate-reducing bacteria. It is further hypothesized that the enzymatic reduction of Cr(VI) would produce relatively pure chromium hydroxide precipitates, whereas indirect reduction would result in mixed Cr-Fe hydroxide solid phases. Flow-through columns containing homogenized sediments from the 100H site at Hanford, WA were subjected to nitrate-, sulfate- or iron-reducing conditions in the presence of 5 µM Cr(VI) and 5 mM lactate. Cr(VI) was depleted in the effluent solutions from the nitrate- and sulfate-reducing columns; however only a small amount of Cr(VI) was removed under iron-reducing conditions. Preliminary analysis of micro X-ray absorption spectra indicate that the untreated and iron-reducing column sediments contained pre-existing Cr in the form of primary minerals, e.g. chromite and/or Cr-bearing micas. However, there was an increase in the relative abundance of mixed-phase Cr-Fe hydroxides, i.e., Cr1-xFex(OH)3 in the nitrate- and sulfate-treated columns. A possible explanation for the observations is that the production of Fe(II) was enhanced under the nitrate- and sulfate- reducing conditions, and was most likely sulfide-driven in the latter case. The Fe(II) was subsequently available for reduction of Cr(VI) resulting in the mixed-phase precipitates. The results from the spectroscopic analysis support the hypothesis that Fe(II)-mediated Cr reduction prevails over direct

  6. Mutagenic and carcinogenic actions of chromium and its compounds. (United States)

    Mamyrbaev, Arstan Abdramanovich; Dzharkenov, Timur Agataevich; Imangazina, Zina Amangalievna; Satybaldieva, Umit Abulkhairovna


    Numerous experimental observations have been made on microorganisms and culture of the cells of mammals as well as the accounting of the chromosomal aberrations in the bone marrow cells of the mammals and of human cells displayed that the chromium and its compounds possess a pronounced mutagenic effect. Translocation test, induction record of DNA damage and repair systems in the mammalian and human cells with greater precision proves the presence of the mutagenic effect of the chromium and its compounds, which in turn is dependent on dose and time of this metal intoxication. Chromium and its compounds have pronounced mutagenic effect, on increased admission to organism of mammals and protozoa.

  7. Microbial biotechnology for remediation of aquatic habitats polluted with chromium


    Viorica Coşier; I. Valentin Petrescu-Mag


    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 mutage...

  8. Microbial Diversity of Chromium-Contaminated Soils and Characterization of Six Chromium-Removing Bacteria (United States)

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


    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.

  9. [Blood and urine chromium: compared values between chromium exposed workers and common people]. (United States)

    Provenzani, A; Verso, M G; Picciotto, D


    Aim of present study is the valutation and quantification of chromium in blood and urine. We compared 3 groups of persons formed by building workers, in particular masons, because cement contains potassium chromate that is dangerous for health, and by common people: urban population and outside the town population. In fact, exposure to CrVI risk is high for people who live near chromate industries. We maked a medical examination, blood and instrumental tests, chromium measuring in blood (recent exposure indicator) and urine (recent and previous indicator). Then we used statistical methods to estimate obtained values of blood and urine chromium among professional exposed people and common people. At the end we think that preventive measures in working environment reduced exposure to CrVI but environmental exposure (for example road dust from catalytic converter erosion, from brake lining erosion, cement dust and tobacco smoke), in the last years, has increased. So there are no difference between urban population and outside the town population and there are also no difference with professional exposed people for work prevention according to law in force, that let down professional risk using safe limits.

  10. Seawater and Chromium Isotopes - a Link to Atmospheric Weathering on Land? (United States)

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


    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 (<0.23 μm) of the heavily suspend-loaded creeks and rivers with likely negatively fractionated (δ53Cr values reflecting the weathered soils. Samples from along the Paraná River, including a sample from the estuary, are all positively fractionated (δ53Cr 0 +0.12 - +0.45 ‰) and closely approach the first values measured by us for contemporaneous seawater (δ53Cr = +0.2 - +0.5 ‰). Our results indicate that

  11. 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


    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.

  12. Effects of p53 knockout on ochratoxin A-induced genotoxicity in p53-deficient gpt delta mice. (United States)

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


    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.

  13. P53 Mdm2 Inhibitors

    NARCIS (Netherlands)

    Khoury, Kareem; Doemling, Alex


    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

  14. ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage


    Chen, Lihong; Gilkes, Daniele M.; Pan, Yu; Lane, William S; Chen, Jiandong


    The p53 tumor suppressor is activated after DNA damage to maintain genomic stability and prevent transformation. Rapid activation of p53 by ionizing radiation is dependent on signaling by the ATM kinase. MDM2 and MDMX are important p53 regulators and logical targets for stress signals. We found that DNA damage induces ATM-dependent phosphorylation and degradation of MDMX. Phosphorylated MDMX is selectively bound and degraded by MDM2 preceding p53 accumulation and activation. Reduction of MDMX...

  15. p53 Downregulates Its Activating Vaccinia-Related Kinase 1, Forming a New Autoregulatory Loop



    The stable accumulation of p53 is detrimental to the cell because it blocks cell growth and division. Therefore, increases in p53 levels are tightly regulated, mainly by its transcriptional target, mdm2, that downregulates p53. Elucidation of new signaling pathways requires the characterization of the members and the nature of their connection. Vaccinia-related kinase 1 (VRK1) contributes to p53 stabilization by partly interfering with its mdm2-mediated degradation, among other mechanisms; th...

  16. Possible adverse effect of chromium in occupational exposure of tannery workers. (United States)

    Kornhauser, Carlos; Wróbel, Katarzyna; Wróbel, Kazimierz; Malacara, Juan Manuel; Nava, Laura Eugenia; Gómez, Leobardo; González, Rita


    Our aim was to investigate the adverse effects of occupational exposure to trivalent chromium. We measured chromium and iron levels in serum and urine and hemoglobin levels in tannery workers and unexposed persons. We studied three groups of subjects. Group 1 included 15 non-smoking male tannery workers highly exposed to chromium from tanning and retanning departments. Group 2 included 14 non-smoking male tannery workers with moderate chromium exposure from dying, drying and finishing departments. Group 3 included 11 healthy, non-smoking male subjects without direct chromium exposure. Higher serum chromium levels were observed in groups 1 and 2 with respect to group 3 (mean values respectively: 0.43; 0.25 and 0.13 microg x l(-1)). Urine chromium levels in group 1 were higher than those in controls (mean values: 1.78 and 1.35 microg x l(-1)). In group 1 an inverse association was found between serum chromium and urine iron (-0.524), urine chromium and hemoglobin (-0.594) and between the urine chromium to iron ratio and hemoglobin (-0.693, p<0.05). The results suggest a chromium adverse effect on iron metabolism, possibly associated with excessive body chromium accumulation. In conclusion, chromium urine test could be recommended for diagnosis of chromium adverse effect on iron metabolism. Further studies are needed to quantify the relationship between urine chromium and hemoglobin metabolism.

  17. 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


    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.

  18. p53 in stem cells

    Institute of Scientific and Technical Information of China (English)

    Valeriya; Solozobova; Christine; Blattner


    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.

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

    CERN Document Server

    Bhatt, Divesh; Bahar, Ivet


    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.

  20. 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


    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.

  1. Reverting p53 activation after recovery of cellular stress to resume with cell cycle progression. (United States)

    Lazo, Pedro A


    The activation of p53 in response to different types of cellular stress induces several protective reactions including cell cycle arrest, senescence or cell death. These protective effects are a consequence of the activation of p53 by specific phosphorylation performed by several kinases. The reversion of the cell cycle arrest, induced by p53, is a consequence of the phosphorylated and activated p53, which triggers its own downregulation and that of its positive regulators. The different down-regulatory processes have a sequential and temporal order of events. The mechanisms implicated in p53 down-regulation include phosphatases, deacetylases, and protein degradation by the proteasome or autophagy, which also affect different p53 protein targets and functions. The necessary first step is the dephosphorylation of p53 to make it available for interaction with mdm2 ubiquitin-ligase, which requires the activation of phosphatases targeting both p53 and p53-activating kinases. In addition, deacetylation of p53 is required to make lysine residues accessible to ubiquitin ligases. The combined action of these downregulatory mechanisms brings p53 protein back to its basal levels, and cell cycle progression can resume if cells have overcome the stress or damage situation. The specific targeting of these down-regulatory mechanisms can be exploited for therapeutic purposes in cancers harbouring wild-type p53.

  2. Human Immunodeficiency Virus Type 1 Nef Binds to Tumor Suppressor p53 and Protects Cells against p53-Mediated Apoptosis



    The nef gene product of human immunodeficiency virus type 1 (HIV-1) is important for the induction of AIDS, and key to its function is its ability to manipulate T-cell function by targeting cellular signal transduction proteins. We reported that Nef coprecipitates a multiprotein complex from cells which contains tumor suppressor protein p53. We now show that Nef interacts directly with p53. Binding assays showed that an N-terminal, 57-residue fragment of Nef (Nef 1-57) contains the p53-bindin...

  3. p53 and mitochondrial dysfunction: novel insight of neurodegenerative diseases. (United States)

    Dai, Chun-Qiu; Luo, Ting-Ting; Luo, Shi-Cheng; Wang, Jia-Qi; Wang, Sheng-Ming; Bai, Yun-Hu; Yang, Yan-Ling; Wang, Ya-Yun


    Mitochondria are organelles responsible for vital cell functions. p53 is a transcription factor that regulates the DNA stability and cell growth normality. Recent studies revealed that p53 can influence mitochondrial function changing from normal condition to abnormal condition under different stress levels. In normal state, p53 can maintain mitochondrial respiration through transactivation of SCO2. When stress stimuli presents, SCO2 overexpresses and leads to ROS generation. ROS promotes p53 inducing MALM (Mieap-induced accumulation of lysosome-like organelles within mitochondria) to repair dysfunctional mitochondria and MIV (Mieap-induced vacuole) to accomplish damaged mitochondria degradation. If stress or damage is irreversible, p53 will translocate to mitochondria, leading into apoptosis or necrosis. Neurodegenerative diseases including Parkinson's disease, Huntington's disease and Alzheimer's disease are still lack of clear explanations of mechanisms, but more studies have revealed the functional relationship between mitochondria and p53 towards the pathological development of these diseases. In this review, we discuss that p53 plays the vital role in the function of mitochondria in the aspect of pathological change metabolism. We also analyze these diseases with novel targeted treating molecules which are related to p53 and mitochondria, hoping to present novel therapies in future clinic.

  4. Thermodynamic Equilibrium Diagrams of Sulphur-Chromium System

    Institute of Scientific and Technical Information of China (English)


    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.

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

    Directory of Open Access Journals (Sweden)

    J. Suchoń


    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.


    Energy Technology Data Exchange (ETDEWEB)



    {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

  7. Chromium Ions Improve Moisure Resistance of Epoxy Resins (United States)

    St. Clair, A. K.; St. Clair, T. L.; Stoakley, D. M.; Singh, J. J.; Sprinkle, D. R.


    Broad spectrum of thermosetting epoxy resins used on commercial and military aircraft, primarily as composite matrices and adhesives. In new technique, chromium-ion containing epoxy with improved resistance to moisture produced where chromium ions believed to prevent absorption of water molecules by coordinating themselves to hydroxyl groups on epoxy chain. Anticipated that improved epoxy formulation useful as composite matrix resin, adhesive, or casting resin for applications on commercial and advanced aircraft. Improvement made without sacrifice in mechanical properties of polymer.

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


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


    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...

  9. 40 CFR Appendix Xii to Part 266 - Nickel or Chromium-Bearing Materials that may be Processed in Exempt Nickel-Chromium Recovery... (United States)


    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Nickel or Chromium-Bearing Materials that may be Processed in Exempt Nickel-Chromium Recovery Furnaces XII Appendix XII to Part 266... FACILITIES Pt. 266, App. XII Appendix XII to Part 266—Nickel or Chromium-Bearing Materials that may...

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


    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.

  11. 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.

  12. Coupling of Nanoporous Chromium, Aluminium-Containing Silicates with an Ionic Liquid for the Transformation of Glucose into 5-(Hydroxymethyl-2-furaldehyde

    Directory of Open Access Journals (Sweden)

    Anabela A. Valente


    Full Text Available Micro/mesoporous chromium, aluminium-containing silicates of the type TUD-1 (Al-TUD-1, Cr-TUD-1, CrAl-TUD-1 and zeolite BEA, Cr-BEA, and related composites BEA/TUD-1 and Cr-BEA/TUD-1, were prepared, characterised, and tested as solid acids coupled with the ionic liquid (IL 1-butyl-3-methylimidazolium chloride ([bmim]Cl as solvent, in the transformation of d-glucose into 5-(hydroxymethyl-2-furaldehyde (Hmf, at 120 °C. The chromium-containing catalytic systems lead to considerably higher Hmf yields in comparison to the related systems without chromium. The IL is a favourable solvent for this target reaction (in terms of Hmf yields reached compared to water or dimethylsulfoxide. A detailed study on the stabilities of the nanoporous solid acids in the IL medium is presented.

  13. Aspirin acetylates wild type and mutant p53 in colon cancer cells: identification of aspirin acetylated sites on recombinant p53. (United States)

    Ai, Guoqiang; Dachineni, Rakesh; Kumar, D Ramesh; Marimuthu, Srinivasan; Alfonso, Lloyd F; Bhat, G Jayarama


    Aspirin's ability to inhibit cell proliferation and induce apoptosis in cancer cell lines is considered to be an important mechanism for its anti-cancer effects. We previously demonstrated that aspirin acetylated the tumor suppressor protein p53 at lysine 382 in MDA-MB-231 human breast cancer cells. Here, we extended these observations to human colon cancer cells, HCT 116 harboring wild type p53, and HT-29 containing mutant p53. We demonstrate that aspirin induced acetylation of p53 in both cell lines in a concentration-dependent manner. Aspirin-acetylated p53 was localized to the nucleus. In both cell lines, aspirin induced p21(CIP1). Aspirin also acetylated recombinant p53 (rp53) in vitro suggesting that it occurs through a non-enzymatic chemical reaction. Mass spectrometry analysis and immunoblotting identified 10 acetylated lysines on rp53, and molecular modeling showed that all lysines targeted by aspirin are surface exposed. Five of these lysines are localized to the DNA-binding domain, four to the nuclear localization signal domain, and one to the C-terminal regulatory domain. Our results suggest that aspirin's anti-cancer effect may involve acetylation and activation of wild type and mutant p53 and induction of target gene expression. This is the first report attempting to characterize p53 acetylation sites targeted by aspirin.

  14. 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: [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)


    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.

  15. CH-53K Heavy Lift Replacement Helicopter (CH-53K) (United States)


    Engineering Development Model ( EDM ) October 27, 2015 which commenced the CH-53K Systems Development and Demonstration Test Program. Currently two of...the four required test EDMs are in a test flight status. There are no significant software-related issues with this program at this time. CH-53K...cost variance is due to Test & Evaluation for Gearbox Engineering Support for Engineering Design Model ( EDM ) 1 First Flight and for Ground Test Vehicle

  16. Lime enhanced chromium removal in advanced integrated wastewater pond system. (United States)

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


    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.

  17. 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;


    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...

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

    Markiewicz, Barbara; Komorowicz, Izabela; Barałkiewicz, Danuta


    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.

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

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


    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

  20. [Chromium content in foods and dietary intake estimation in the Northwest of Mexico]. (United States)

    Grijalva Haro, M I; Ballesteros Vázquez, M N; Cabrera Pacheco, R M


    Chromium is an indispensable nutrient for the carbohydrates and lipids metabolism. In this study the chromium content in the twenty main foods of the diet from Northwestern Mexico was determined, as well as the daily mean intake which was estimated based on the food intake basket of this region. Chromium content was analyzed by atomic absorption spectrophotometry using the graphite furnace technique and previous digestion of foods in microwave oven. The chromium mean intake was estimated considering the chromium daily mean intake for person per day and the chromium content of the foods analyzed in this study. The range chromium content in the foods analyzed was between 0.0004 and 0.1641 microgram/g dry weight. White cheese showed the highest chromium content followed by pasta soup, wheat tortilla, bread and meat. The main foods chromium contributors in the diet were: wheat tortilla (20%), white cheese (11%), corn tortilla (11%), pasta soup (10%), milk (10%), meat (9%) and white bread (8%). The daily chromium intake was 30.43 +/- 1.6 micrograms/d. Chromium values obtained in the food analyzed are considered low. Moreover, chromium intake obtained from the diet is not enough to meet the safety and adequate daily chromium intake. Therefore, the population from the Northwestern Mexico has a suboptimal dietary chromium intake.

  1. A positive feedback loop of p53/miR-19/TP53INP1 modulates pancreatic cancer cell proliferation and apoptosis. (United States)

    Wang, Xiaofang; Wang, Lei; Mo, Qingjiang; Jia, Ankui; Dong, Yuqian; Wang, Guoqiang


    Pancreatic cancer is a common malignancy whose prognosis and treatment of pancreatic cancer is extremely poor, with only 20% of patients reaching two years of survival. Previous findings have shown that the tumor suppressor p53 is involved in the development of various types of cancer, including pancreatic cancer. Additionally, p53 is able to activate TP53INP1 transcription by regulating several phenotypes of cancer cells. Using gain and loss-of-function assays, the aim of the present study was to examine the relationships between miR-19a/b and cancer development as well as potential underlying mechanisms. The results showed that miR-19a/b identified a positive feedback regulation of p53/TP53INP1 axis. Additionally, p53 upregulated the TP53INP1 level in pancreatic cancer cells. However, overexpressed miR-19a/b partially restored the TP53 function in the pancreatic cancer cells while miR-19a/b downregulated TP53INP1 protein by directly targeting 3'UTR of its mRNA at the post-transcriptional level. In addition, the patient tissues identified that the miR-19a/b level in pancreatic cancer tissues was conversely correlated with TP53 and TP53INP1 expression. The results provide evidence for revealing the molecular mechanism involved in the development of pancreatic cancer and may be useful in the identification of new therapeutic targets for pancreatic cancer.

  2. Gain of cellular adaptation due to prolonged p53 impairment leads to functional switchover from p53 to p73 during DNA damage in acute myeloid leukemia cells. (United States)

    Chakraborty, Juni; Banerjee, Shuvomoy; Ray, Pallab; Hossain, Dewan Md Sakib; Bhattacharyya, Sankar; Adhikary, Arghya; Chattopadhyay, Sreya; Das, Tanya; Sa, Gaurisankar


    Tumor suppressor p53 plays the central role in regulating apoptosis in response to genotoxic stress. From an evolutionary perspective, the activity of p53 has to be backed up by other protein(s) in case of any functional impairment of this protein, to trigger DNA damage-induced apoptosis in cancer cells. We adopted multiple experimental approaches to demonstrate that in p53-impaired cancer cells, DNA damage caused accumulation of p53 paralogue p73 via Chk-1 that strongly impacted Bax expression and p53-independent apoptosis. On the contrary, when p53 function was restored by ectopic expression, Chk-2 induced p53 accumulation that in turn overshadowed p73 activity, suggesting an antagonistic interaction between p53 family members. To understand such interaction better, p53-expressing cells were impaired differentially for p53 activity. In wild-type p53-expressing cancer cells that were silenced for p53 for several generations, p73 was activated, whereas no such trend was observed when p53 was transiently silenced. Prolonged p53 interference, even in functional p53 settings, therefore, leads to the "gain of cellular adaptation" in a way that alters the cellular microenvironment in favor of p73 activation by altering p73-regulatory proteins, e.g. Chk1 activation and dominant negative p73 down-regulation. These findings not only unveil a hitherto unexplained mechanism underlying the functional switchover from p53 to p73, but also validate p73 as a promising and potential target for cancer therapy in the absence of functional p53.

  3. 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: [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: [Department of pathology, The Chinese University of Hong Kong, Hong Kong (China)


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Morris, Suzanne M. [Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079 (United States)], E-mail:; Akerman, Gregory S. [Toxicology Branch, Health Effects Division (7509P), US Environmental Protection Agency, 1200 Pennsylvania Avenue, NW, Washington, DC 20460 (United States); Desai, Varsha G. [Division of Systems Toxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079 (United States); Tsai, Chen-an [Biostatistics Center and Department of Public Health, China Medical University, Taichung, 40402, Taiwan (China); Tolleson, William H.; Melchior, William B. [Division of Biochemical Toxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079 (United States); Lin, Chien-Ju [Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079 (United States); Fuscoe, James C. [Division of Systems Toxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079 (United States); Casciano, Daniel A. [Dan Casciano and Associates, 47 Marcella Drive, Little Rock, AR 72233 (United States); Chen, James J. [Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079 (United States)


    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{sup -/-} and p53{sup +/-} mice. Six male mice from each genotype (p53{sup +/+}, p53{sup +/-}, and p53{sup -/-}) 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{sup +/+} and p53{sup +/-} or between p53{sup +/+} and p53{sup -/-} at the level of p {<=} 0.05. Both genes with increased expression and decreased expression were identified in p53{sup +/-} and in p53{sup -/-} mice. Most notable in the gene list derived from the p53{sup +/-} mice was the significant reduction in p53 mRNA. In the p53{sup -/-} 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.

  5. Chromium-chromium interaction in a binuclear mixed-valent Cr(I)-Cr(II) complex. (United States)

    Alzamly, Ahmed; Gorelsky, Serge I; Gambarotta, Sandro; Korobkov, Ilia; Le Roy, Jennifer; Murugesu, Muralee


    A mixed-valent Cr(I)-Cr(II) binuclear complex, {κ(1),κ(2),κ(3)-N,P,P-cyclo[(Ph)PCH2N(CH2Ph)CH2]}2(CrCl2)[Cr(μ-Cl)(AlClMe2)]·4toluene (1), of a P2N2 cyclic ligand was obtained upon treatment of the chromium precursor with alkylaluminum. Complex 1 was accessible from either its trivalent or divalent precursors, and density functional theory calculations revealed the presence of only σ- and π-orbital interactions in the Cr-Cr bond.

  6. KSHV latent protein LANA2 inhibits sumo2 modification of p53 (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


    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


    Directory of Open Access Journals (Sweden)

    C. C. Lima


    Full Text Available The present study evaluated the growth of nursling Nelore calves supplemented with chromium during creep feeding. The study was conducted using 131 Nelore calves with an average age of 60 days and average adjusted initial weight of 75 kg; considering that all calves were accompanied by their mothers. Therefore, the experimental groups were defined as T1: 35 males supplemented with chromium; T2: 34 males without chromium, T3: 30 females supplemented with chromium and T4: 32 females supplemented without chromium. The experimental period lasted from 60 days of age to 210 days (weaning, the animals were kept in two pickets of Panicum maximum cv. Mombasa provided with troughs for the creep feeding system, which permitted calves exclusive access to the concentrate formula based on 75% of TDN and 20% of crude protein, with 35% of soybean meal, 63% of corn and 2% of mineral nucleus containing 10 mg of chromium chelate for each kg of the product. The data were subjected to the analysis of variance, using the software R (R Development Core Team, 2013. In the evaluation of the live weight at 150 days of age, no significant difference was found in the use of chromium in males and females (regardless of sex. However, in the analysis between sexes, females’ live weights were lower than males’ live weight (p = 0.04, being 131.1 kg and 138.1 kg respectively. In the evaluation of live weight at 210 days there was no significant difference between males and females (p = 0.07, but there was a difference (p = 0.03 in the use of chrome in the evaluated treatments. So, it could be concluded that the creep feeding system with chrome chelate supplementation promoted an improvement in male and females calves’ growth for average daily weight gain and weaning weight, with a positive influence on the weight of cows.

  8. Nitridation of chromium powder in ammonia atmosphere

    Institute of Scientific and Technical Information of China (English)

    Ling Li; Qiang Zhen; Rong Li


    CrN powder was synthesized by nitriding Cr metal in ammonia gas flow, and its chemical reaction mechanism and nitridation process were studied. Through thermodynamic calculations, the Cr−N−O predominance diagrams were constructed for different tempera-tures. Chromium nitride formed at 700−1200°C under relatively higher nitrogen and lower oxygen partial pressures. Phases in the products were then investigated using X-ray diffraction (XRD), and the Cr2N content varied with reaction temperature and holding time. The results indicate that the Cr metal powder nitridation process can be explained by a diffusion model. Further, Cr2N formed as an intermediate product because of an incomplete reaction, which was observed by high-resolution transmission electron microscopy (HRTEM). After nitriding at 1000°C for 20 h, CrN powder with an average grain size of 63 nm was obtained, and the obtained sample was analyzed by using a scanning electron microscope (SEM).

  9. Can elevated chromium induce somatopsychic responses? (United States)

    Lovrincevic, I; Leung, F Y; Alfieri, M A; Grace, D M


    The possible somatopsychological effects of chromium (Cr) was investigated in a population of patients, from a surgical ward of our hospital, who required total parenteral nutrition (TPN) solutions, and who became exposed to various amounts of this metal from this treatment. The study involved a questionnaire as well as biochemical tests which included serum Cr and other selected trace metals. The renal status for all eligible patients was within normal parameters. The patient population varied in age, pathology, surgical treatment, and duration on TPN. The results showed that every patient who received TPN had an increased serum Cr level; some increases were up to 50-fold above the normal reference level for serum Cr. Although statistical analysis failed to show any significant statistical relationship between an increased serum Cr and the investigated somatopsychological disturbances, this effect cannot be ruled out since one case did show all the dream disturbances. Considering these cases, the action of sedative medications that may suppress the effects of Cr, cannot be ruled out. As Cr(III) may be potentially genotoxic at high concentrations, infusion of this metal over long time periods should be avoided. Supplementation of Cr in TPN solutions appears to be unnecessary for short-term TPN because this metal is a known contaminant of these solutions. Efforts are required to find TPN nutrients with low or no Cr contamination.

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

    Directory of Open Access Journals (Sweden)

    Mousumi Sen


    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.

  11. Specific killing of P53 mutated tumor cell lines by a cross-reactive human HLA-A2-restricted P53-specific CTL line

    DEFF Research Database (Denmark)

    Würtzen, P A; Pedersen, L O; Poulsen, H S;


    53(65-73) and p53(187-197) peptides was obtained in the T-cell lines. Interestingly, cold target inhibition experiments demonstrated that the simultaneous recognition of the 2 peptides was the result of cross-reactivity, which was confirmed by killing experiments at the clonal CTL level. Furthermore...

  12. 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: [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan (China)


    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.

  13. The regulation of the p53/MDM2 feedback loop by microRNAs



    Tumor suppressor p53 and its signaling pathway play a central role in tumor prevention. The E3 ubiquitin ligase MDM2, which is a direct p53 transcriptional target and also the most critical negative regulator of p53, forms an autoregulatory negative feedback loop with p53 in the cell to tightly regulate the levels and activity of p53. MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that play a critical role in the post-translational regulation of gene expression. Recent st...

  14. Application of artificial neural network (ANN in Biosorption modeling of Chromium (VI from aqueous solutions

    Directory of Open Access Journals (Sweden)

    F Mohammadi


    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

  15. Spectroscopic study for a chromium-adsorbed montmorillonite (United States)

    Nurtay, Maidina ·; Tuersun, Maierdan ·; Cai, Yuanfeng; Açıkgöz, Muhammed; Wang, Hongtao; Pan, Yuguan; Zhang, Xiaoke; Ma, Xiaomei


    Samples of purified montmorillonite with trace amounts of quartz were subjected to different concentrations of chromium sulphate solutions for one week to allow cation exchange. The chromium-bearing montmorillonites were verified and tested using powder X-ray diffractometry (XRD), X-ray fluorescence spectrometry, electron spin resonance (ESR) spectrometry and Fourier transformation infrared (FTIR) spectroscopy to explore the occupation sites of the chromium. The ESR spectra recorded before and after the chromium exchange show clear differences: a strong and broad resonance with two shoulders at the lower magnetic field side was present to start, and its intensity as well as that of the ferric iron resonance, increased with the concentration of added chromium. The signals introduced by the chromium, for example at g = 1.975 and 2.510 etc., suggested that the chromium had several occupational sites. The ESR peak with g = 2.510 in the second derivative spectrum suggested that Cr3+ was weakly bounded to TOT with the form of [Cr(H2O)3]3+ in hexagonal cavities. This was verified by comparing the FTIR spectra of the pure and modified montmorillonite. The main resonance centred at g = 1.975 indicated that the majority of Cr3+ occupied the interlayer region as [Cr(H2O)6]3+. The substitution of Ca2 + by Cr3+ also greatly affected the vibration of the hydrogens associate to water, ranged from 3500 to 2600 cm-1 in FTIR. Furthermore, the presence of two diffraction lines in the XRD results (specifically those with d-values of 1.5171 and 1.2673 nm) and the calculations of the size of the interlayer space suggested the presence of two types of montmorillonite with different hydration cations in the sample exposed to 0.2 M chromium sulphate. The two diffraction lines were assigned to [Cr(H2O)6]3+ and [Cr(H2O)3O3]3+, respectively. This also suggested that the species of hydration cation was constrained by the concentration of the chromium solution.

  16. A possible role for chromium(III) in genotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Snow, E.T. (New York Univ. Medical Center, Tuxedo (United States))


    Chromium is found in the environment in two major forms: reduced Cr{sup III} and Cr{sup VI}, or chromate. Chromate, the most biologically active species, is readily taken up by living cells and reduced intracellularly, via reactive intermediates, to stable Cr{sup III} species. Cr{sup III}, the most abundant form of chromium in the environment, does not readily cross cell membranes and is relatively inactive in vivo. However, intracellular Cr{sup III} can react slowly with both nucleic acids and proteins and can be genotoxic. The authors have investigated the genotoxicity of Cr{sup III} in vitro using a DNA replication assay and in vivo by CaCl{sub 2}-mediated transfection of chromium-treated DNA into Escherichia coli. These results suggest that Cr{sup III} alters the interaction between the DNA template and the polymerase such that the binding strength of the DNA polymerase is increased and the fidelity of DNA replication is decreased. These interactions may contribute to the mutagenicity of chromium ions in vivo and suggest that Cr{sup III} can contribute to chromium-mediated carcinogenesis.

  17. 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)


    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.

  18. Enhancement of chromium uptake in tanning using oxazolidine. (United States)

    Sundarapandiyan, S; Brutto, Patrick E; Siddhartha, G; Ramesh, R; Ramanaiah, B; Saravanan, P; Mandal, A B


    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.

  19. Bioaccumulation and biosorption of chromium by Aspergillus niger MTCC 2594. (United States)

    Sandana Mala, John Geraldine; Unni Nair, Balachandran; Puvanakrishnan, Rengarajulu


    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.

  20. Microbial exudate promoted dissolution and transformation of chromium containing minerals (United States)

    Saad, E. M.; Sun, J.; Tang, Y.


    Because of its utility in many industrial processes, chromium has become the second most common metal contaminant in the United States. The two most common oxidation states of chromium in nature are Cr(III), which is highly immobile, and Cr(VI), which is highly mobile and toxic. In both natural and engineered environments, the most common remediation of Cr(VI) is through reduction, which results in chromium sequestration in the low solubility mixed Cr(III)-Fe(III) (oxy)hydroxide phases. Consequently, the stability of these minerals must be examined to assess the fate of chromium in the subsurface. We examined the dissolution of mixed Cr(III)-Fe(III) (oxy)hydroxides in the presence of common microbial exudates, including the siderophore desferrioxamine B (DFOB; a common organic ligand secreted by most microbes with high affinity for ferric iron and other trivalent metal ions) and oxalate (a common organic acid produced by microbes). The solids exhibited incongruent dissolution with preferential leaching of Fe from the solid phase. Over time, this leads to a more Cr rich mineral, which is known to be more soluble than the corresponding mixed mineral phase. We are currently investigating the structure of the reacted mineral phases and soluble Cr(III) species, as well as the potential oxidation and remobilization of the soluble Cr species. Results from this study will provide insights regarding the long term transport and fate of chromium in the natural environment in the presence of microbial activities.

  1. p53 and its isoforms in cancer



    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...

  2. Effective bioleaching of chromium in tannery sludge with an enriched sulfur-oxidizing bacterial community. (United States)

    Zeng, Jing; Gou, Min; Tang, Yue-Qin; Li, Guo-Ying; Sun, Zhao-Yong; Kida, Kenji


    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.

  3. Development of a coprecipitation system for the speciation/preconcentration of chromium in tap waters

    Energy Technology Data Exchange (ETDEWEB)

    Karatepe, Aslihan, E-mail: [Nevsehir University, Faculty of Science and Arts, Department of Chemistry, 50000 Nevsehir (Turkey); Korkmaz, Esra [Bozok University, Faculty of Science and Arts, Department of Chemistry, Yozgat (Turkey); Soylak, Mustafa [Erciyes University, Faculty of Science and Arts, Chemistry Department, 38039 Kayseri (Turkey); Elci, Latif [Pamukkale University, Faculty of Science and Arts, Department of Chemistry, 20020 Denizli (Turkey)


    A method for the speciation of chromium(III), chromium(VI) and determination of total chromium based on coprecipitation of chromium(III) with dysprosium hydroxide has been investigated and applied to tap water samples. Chromium(III) was quantitatively recovered by the presented method, while the recovery values for chromium(VI) was below 10%. The influences of analytical parameters including amount of dysprosium(III), pH, centrifugation speed and sample volume for the quantitative precipitation were examined. No interferic effects were observed from alkali, earth alkali and some transition metals for the analyte ions. The detection limits (k = 3, N = 15) were 0.65 {mu}g/L for chromium(III) and 0.78 {mu}g/L for chromium(VI). The validation of the presented method was checked by the analysis of certified reference materials.

  4. Process for improving moisture resistance of epoxy resins by addition of chromium ions (United States)

    St.clair, A. K.; Stoakley, D. M.; St.clair, T. L.; Singh, J. J. (Inventor)


    A process for improving the moisture resistance properties of epoxidized TGMDA and DGEBA resin system by chemically incorporating chromium ions is described. The addition of chromium ions is believed to prevent the absorption of water molecules.


    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...

  6. In vitro binding properties of tumor suppressor p53 with PUMA and NOXA. (United States)

    Park, So Young; Jeong, Mi Suk; Jang, Se Bok


    The p53-upregulated modulator of apoptosis (Puma) and Noxa, are direct targets in p53-mediated apoptosis localized to the mitochondria. Tumor suppressor p53 induces apoptosis by transcriptional induction of Puma and Noxa, which encode proapoptotic BH3-only member Bcl-1 family proteins. However, at a molecular level, the mechanism of action of Puma and Noxa proteins remain poorly defined. In addition, there have been no reports on whether or not p53 directly interacts with Puma and Noxa, in vitro. Here, we provide evidence indicating that the DNA binding domain (DBD) of p53 directly interacted with the BH3 domains of human PUMA and NOXA. Our studies revealed that PUMA has a weak affinity for p53, but NOXA has significant affinity for p53. In this study, we developed a molecular docking model using homology modeling based on the structures of truncated p53, PUMA and NOXA. In addition, we investigated whether or not six mutants of p53 (K101A, T102A, L111A, D186A, G199A and S227A) were able to bind to PUMA and NOXA. Four structure-based mutations (T102A, L111A, D186A and G199A) disrupted the p53-PUMA/NOXA interaction. Our study suggested that these four mutations lowered the stability of the p53 DBD domain and induced aggregation of structurally destabilized p53, and thus disrupted the p53-PUMA/NOXA interaction.

  7. Reduction of chromium oxide from slags

    Directory of Open Access Journals (Sweden)

    Gutiérrez-Paredes, J.


    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

  8. Effects of irradiation on chromium's behavior in ferritic/martensitic FeCr alloy

    Institute of Scientific and Technical Information of China (English)

    Xinfu HE; Wen YANG; Zhehao QU; Sheng FAN


    The effects of irradiation on chromium performance under different temperatures in Fe-20at%Cr were modeled by modified Marlowe code. Chromium precipitation was observed in FeCr alloy after irradiation; interstitial Chromium atoms are the preferred formation of mixed FeCr dumbbells in the direction ofand; interstitial chromium atoms congregated on {111} and {110} plane. The results are compared with experiment observations and are useful to understanding the irradiation performances of FeCr alloy.

  9. A study of the process of desorption of hexavalent chromium

    Directory of Open Access Journals (Sweden)

    W.B. Amorim


    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.

  10. Bioabsorption of chromium from retan chrome liquor by cyanobacteria. (United States)

    Pandi, M; Shashirekha, V; Swamy, Mahadeswara


    The bioaccumulation of chromium from retan chrome liquor by Spirulina fusiformis was investigated under laboratory as well as field conditions. At the optimal conditions, metal ion uptake increased with initial metal ion concentration up to 300mg/l. The effect on various physico-chemical parameters like total solids (TS), total dissolved solids (TDS), total suspended solids (TSS), chlorides, sulphates, phenols, biochemical oxygen demand (BOD) and chemical oxygen demand (COD) and biochemical studies related to biomass, chlorophyll-a and protein were also carried out. The present study indicates that S. fusiformis is very effective in removal of chromium (93-99%) besides removing other toxicants from retan chrome liquor. The sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and FTIR studies indicate the interaction/complexation between Cr and alga. The mechanism involved in bioaccumulation of chromium is also discussed. The process when upgraded can be applied for detoxification of tannery effluents.

  11. Extraction of Chromium from Carbon Ferrochromium Residual Wastes (United States)

    Lazarevskiy, P. P.; Gizatulin, R. A.; Romanenko, Yu E.; Valuev, D. V.; Valueva, A. V.; Serikbol, A.


    This work reports the problem of processing residual wastes after producing carbon ferrochrome by recycling dust using a hydrometallurgical method with the purpose of extracting the basic component - chromium, The X-ray diffraction analysis results, chemical and granulometric compositions of dust from the carbon ferrochrome production are given, The method for the production of chemical-enrichment concentrate (CEC) by processing ferrous dust is described, with obtaining a middling product - sodium mono-chromate with its further reduction to chromium hydroxide, followed by autoclave leaching, and resulting in the production of chemically enriched chrome concentrate, The plant used for autoclave leaching and filtering is schematically depicted, The smelting process of metallic chromium using the ladle aluminothermic method is described,

  12. Studies of removal of chromium by model constructed wetland

    Directory of Open Access Journals (Sweden)

    C. Mant


    Full Text Available Chromium is a pollutant present in tannery wastewater, its removal is necessary for protection of the environment. Penisetum purpureum, Brancharia decumbens and Phragmites australis were grown hydroponically in experimental gravel beds to determine their potential for the phytoremediation of solutions containing 10 and 20 mg Cr dm-3. These concentrations, similar to tannery wastewater after initial physico-chemical treatment were used with the aim of developing an economic secondary treatment to protect the environment. All the systems achieved removal efficiencies of 97 - 99.6% within 24 hours. P. purpureum and B. decumbens removed 78.1% and 68.5% respectively within the first hour. Both P. purpureum and B. decumbens were tolerant of the concentrations of chromium applied, but P. purpureum showed the greatest potential because its faster growth and larger biomass achieved a much greater chromium removal over the whole length of time of the experiment.

  13. 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)


    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}).

  14. Chromium Resistant Bacteria: Impact on Plant Growth in Soil Microcosm

    Directory of Open Access Journals (Sweden)

    Sayel Hanane


    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.

  15. Genome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhancers controlled by a lncRNA

    NARCIS (Netherlands)

    Léveillé, Nicolas; Melo, Carlos A; Rooijers, Koos; Díaz-Lagares, Angel; Melo, Sonia A; Korkmaz, Gozde; Lopes, Rui; Akbari Moqadam, Farhad; Maia, Ana R; Wijchers, Patrick J; Geeven, Geert; den Boer, Monique L; Kalluri, Raghu; de Laat, Wouter; Esteller, Manel; Agami, Reuven


    p53 binds enhancers to regulate key target genes. Here, we globally mapped p53-regulated enhancers by looking at enhancer RNA (eRNA) production. Intriguingly, while many p53-induced enhancers contained p53-binding sites, most did not. As long non-coding RNAs (lncRNAs) are prominent regulators of chr

  16. Genome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhancers controlled by a lncRNA

    NARCIS (Netherlands)

    N. Léveillé (Nicolas); C.A. Melo (Carlos); K. Rooijers (Koos); A. Díaz-Lagares (Angel); S.A. Melo (Sonia A.); G. Korkmaz (Gozde); R. Lopes (Rui); F.A. Moqadam; A.R.R. Maia (Ana); P.J. Wijchers (Patrick); G. Geeven (Geert); M.L. den Boer (Monique); R. Kalluri (Raghu); W.L. de Laat (Wouter); M. Esteller (Manel); R. Agami (Reuven)


    textabstractp53 binds enhancers to regulate key target genes. Here, we globally mapped p53-regulated enhancers by looking at enhancer RNA (eRNA) production. Intriguingly, while many p53-induced enhancers contained p53-binding sites, most did not. As long non-coding RNAs (lncRNAs) are prominent regul

  17. 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.


    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......, the stabilities of reductant and luminol solutions were studied. The linear range of the calibration curve for chromium(III) and chromium(VI) was 1-400 mu g l(-1). The detection limit was 0.12 mu g l(-1) for chromium(III) and 0.09 mu g l(-1) for chromium(VI), respectively. The precision at the 20 mu g l(-1) level...... was 1.4% for chromium(III) and 2.5% for chromium(VI), respectively. The accuracy of the chromium(III) determination was determined by analysis of the NIST standard reference material 1643c, Trace elements in water with the result 19.1 +/- 1.0 mu g Cr(III) l(-1) (certified value 19.0 +/- 0.6 mu g Cr...

  18. 21 CFR 73.3110a - Chromium-cobalt-aluminum oxide. (United States)


    ... 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....

  19. Chromium isotopes in siliciclastic sediments and sedimentary rocks as a proxy for Earth surface redox (United States)

    Reinhard, C. T.; Planavsky, N. J.; Wang, X.; Owens, J. D.; Johnson, T. M.; Fischer, W. W.; Lyons, T. W.


    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

  20. Processes controlling the chromium isotopic composition of river water: Constraints from basaltic river catchments (United States)

    D'Arcy, Joan; Babechuk, Michael G.; Døssing, Lasse Nørbye; Gaucher, Claudio; Frei, Robert


    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

  1. Experimental study on 830 MPa grade pipeline steel containing chromium

    Institute of Scientific and Technical Information of China (English)

    Yi Ren; Shuai Zhang; Shuang Wang; Wen-yue Liu


    The diversity of microstructure and properties of 830 Mpa grade pipeline steel containing chromium was investigated by optical microscope and transmission electron microscopy. The main microstructures were multiple configurations, containing lath bainite and granule bainite. Mechanical properties test results showed that the yield strength and tensile strength improved with in-creasing chromium content. The toughness and elongation decreased at the same time, so temper process was introduced. Appling proper temper parameters, the values of toughness and elongation were improved dramatically, and the strength decreased slightly.

  2. Fractionation behavior of chromium isotopes during coprecipitation with calcium carbonate

    DEFF Research Database (Denmark)

    Rodler, Alexandra; Sánchez-Pastor, Nuria; Fernández-Díaz, Lurdes;


    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 paleoenviro......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...

  3. Use of chitosan for chromium removal from exhausted tanning baths. (United States)

    Cesaro, Raffaele; Fabbricino, Massimiliano; Lanzetta, Rosa; Mancino, Anna; Naviglio, Biagio; Parrilli, Michelangelo; Sartorio, Roberto; Tomaselli, Michele; Tortora, Gelsomina


    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. Primary and secondary crystallization of modified hypoeutectic chromium cast iron

    Directory of Open Access Journals (Sweden)

    A. Studnicki


    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.

  5. Urinary levels of nickel and chromium associated with dental restoration by nickel-chromium based alloys. (United States)

    Chen, Bo; Xia, Gang; Cao, Xin-Ming; Wang, Jue; Xu, Bi-Yao; Huang, Pu; Chen, Yue; Jiang, Qing-Wu


    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.

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

    Directory of Open Access Journals (Sweden)

    B. Dheeba


    Full Text Available 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.

  7. Spatial distribution of chromium in soils contaminated by chromium-containing slag

    Institute of Scientific and Technical Information of China (English)

    HUANG Shun-hong; PENG Bing; YANG Zhi-hui; CHAI Li-yuan; XU You-ze; SU Chang-qing


    To evaluate the metal chromium (Cr) contamination of soil at a chromium-containing slag site by ferrochromium production, the contaminated sites, under slag heap, in the vicinity of slag heap and arable soils near the outlet of sewer channel, and unpolluted site 5 km away from one ferroalloy plant in Hunan Province, China, were selected. The concentrations of total Cr and water soluble Cr in bulk soil samples and profile depth samples were determined. The results show that the soils in the vicinity of slag heap have the highest total Cr content followed by the soils under the slag heap and near the outlet of sewer channel of the factory. The mean concentrations of total Cr in the top soils at above three contaminated locations exceed the critical level of Secondary Environmental Quality Standard for Soil in China by 3.5, 5.4 and 1.8 times. In most Cr polluted soils, total Cr has a relative accumulation in soil depth of 40-60 cm, but this trend is not found in unpolluted soils. The average concentrations of water soluble Cr (Ⅵ) in top soils under slag heap and in the vicinity of slag heap are 176.9 times and 52.7 times higher than that in the uncontaminated soils, respectively. However, water soluble Cr (Ⅵ) contents in soils near sewer channel are all low and the values are close to that in the uncontaminated soils. Although water soluble Cr (Ⅵ) content in soil profiles decreases with soil depths, it in soils under slag heap maintains a high level even at a depth of 100-150 cm. The results imply that the transportation of Cr (Ⅵ) can result in a potential risk of groundwater system in this area.

  8. The expanding regulatory universe of p53 in gastrointestinal cancer. (United States)

    Fesler, Andrew; Zhang, Ning; Ju, Jingfang


    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.

  9. TP53 Mutations in Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Akira Mogi


    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.

  10. Suppression of p53 activity through the cooperative action of Ski and histone deacetylase SIRT1. (United States)

    Inoue, Yasumichi; Iemura, Shun-ichiro; Natsume, Tohru; Miyazawa, Keiji; Imamura, Takeshi


    Ski was originally identified as an oncogene based on the fact that Ski overexpression transformed chicken and quail embryo fibroblasts. Consistent with these proposed oncogenic roles, Ski is overexpressed in various human tumors. However, whether and how Ski functions in mammalian tumorigenesis has not been fully investigated. Here, we show that Ski interacts with p53 and attenuates the biological functions of p53. Ski overexpression attenuated p53-dependent transactivation, whereas Ski knockdown enhanced the transcriptional activity of p53. Interestingly, Ski bound to the histone deacetylase SIRT1 and stabilized p53-SIRT1 interaction to promote p53 deacetylation, which subsequently decreased the DNA binding activity of p53. Consistent with the ability of Ski to inactivate p53, overexpressing Ski desensitized cells to genotoxic drugs and Nutlin-3, a small-molecule antagonist of Mdm2 that stabilizes p53 and activates the p53 pathway, whereas knocking down Ski increased the cellular sensitivity to these agents. These results indicate that Ski negatively regulates p53 and suggest that the p53-Ski-SIRT1 axis is an attractive target for cancer therapy.

  11. Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53 (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


    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

  12. Specific TP53 Mutants Overrepresented in Ovarian Cancer Impact CNV, TP53 Activity, Responses to Nutlin-3a, and Cell Survival

    Directory of Open Access Journals (Sweden)

    Lisa K. Mullany


    Full Text Available Evolutionary Action analyses of The Cancer Gene Atlas data sets show that many specific p53 missense and gain-of-function mutations are selectively overrepresented and functional in high-grade serous ovarian cancer (HGSC. As homozygous alleles, p53 mutants are differentially associated with specific loss of heterozygosity (R273; chromosome 17; copy number variation (R175H; chromosome 9; and up-stream, cancer-related regulatory pathways. The expression of immune-related cytokines was selectively related to p53 status, showing for the first time that specific p53 mutants impact, and are related to, the immune subtype of ovarian cancer. Although the majority (31% of HGSCs exhibit loss of heterozygosity, a significant number (24% maintain a wild-type (WT allele and represent another HGSC subtype that is not well defined. Using human and mouse cell lines, we show that specific p53 mutants differentially alter endogenous WT p53 activity; target gene expression; and responses to nutlin-3a, a small molecular that activates WT p53 leading to apoptosis, providing “proof of principle” that ovarian cancer cells expressing WT and mutant alleles represent a distinct ovarian cancer subtype. We also show that siRNA knock down of endogenous p53 in cells expressing homozygous mutant alleles causes apoptosis, whereas cells expressing WT p53 (or are heterozygous for WT and mutant p53 alleles are highly resistant. Therefore, despite different gene regulatory pathways associated with specific p53 mutants, silencing mutant p53 might be a suitable, powerful, global strategy for blocking ovarian cancer growth in those tumors that rely on mutant p53 functions for survival. Knowing p53 mutational status in HGSC should permit new strategies tailored to control this disease.

  13. Homozygous and Heterozygous p53 Knockout Rats Develop Metastasizing Sarcomas with High Frequency (United States)

    van Boxtel, Ruben; Kuiper, Raoul V.; Toonen, Pim W.; van Heesch, Sebastiaan; Hermsen, Roel; de Bruin, Alain; Cuppen, Edwin


    The TP53 tumor suppressor gene is mutated in the majority of human cancers. Inactivation of p53 in a variety of animal models results in early-onset tumorigenesis, reflecting the importance of p53 as a gatekeeper tumor suppressor. We generated a mutant Tp53 allele in the rat using a target-selected mutagenesis approach. Here, we report that homozygosity for this allele results in complete loss of p53 function. Homozygous mutant rats predominantly develop sarcomas with an onset of 4 months of age with a high occurrence of pulmonary metastases. Heterozygous rats develop sarcomas starting at 8 months of age. Molecular analysis revealed that these tumors exhibit a loss-of-heterozygosity of the wild-type Tp53 allele. These unique features make this rat highly complementary to other rodent p53 knockout models and a versatile tool for investigating tumorigenesis processes as well as genotoxic studies. PMID:21854749

  14. Physiological, biochemical and histometric responses of Nile tilapia (Oreochromis niloticus L.) by dietary organic chromium (chromium picolinate) supplementation



    Chromium has been recognized as a new and important micro-nutrient, essential for both human and animal nutrition. This study was conducted to evaluate the appropriateness and/or the use of safety level of dietary chromium picolinate (Cr-Pic), and its effects on the physiological responses, the histometric characteristics, and the chemical analysis of dorsal muscles of mono-sex Nile tilapia, Oreochromis niloticus. A total of 420 fingerlings (28.00 ± 0.96 g) were randomly distributed into 21 f...

  15. The isotopic composition of authigenic chromium in anoxic marine sediments: A case study from the Cariaco Basin (United States)

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


    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.

  16. Chromium(VI) release from leather and metals can be detected with a diphenylcarbazide spot test

    DEFF Research Database (Denmark)

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


    Along with chromium, nickel and cobalt are the clinically most important metal allergens. However, unlike for nickel and cobalt, there is no validated colorimetric spot test that detects chromium. Such a test could help both clinicians and their patients with chromium dermatitis to identify culprit...... at 0.5 ppm without interference from other pure metals, alloys, or leather. A market survey using the test showed no chromium(VI) release from work tools (0/100). However, chromium(VI) release from metal screws (7/60), one earring (1/50), leather shoes (4/100) and leather gloves (6/11) was observed. We...

  17. The oxidation and reduction of chromium of stainless steels in an eletric arc furnace

    Directory of Open Access Journals (Sweden)

    B. Arh


    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.

  18. PIN1 in hepatocellular carcinoma is associated with TP53 gene status. (United States)

    Bae, Jun Sang; Noh, Sang Jae; Kim, Kyoung Min; Jang, Kyu Yun; Park, Ho Sung; Chung, Myoung Ja; Park, Byung-Hyun; Moon, Woo Sung


    Phosphorylation of proteins on serine/threonine residues that precede proline (pSer/Thr-Pro) is specifically catalyzed by the peptidyl-prolyl cis-trans isomerase PIN1. PIN1-mediated prolyl-isomerization induces cell cycle arrest and growth inhibition through the regulation of target proteins, including TP53. We examined whether PIN1 acts in a different manner according to TP53 gene status in hepatocellular carcinoma (HCC). We investigated the expression of PIN1 and TP53 proteins in 119 HCC tissue samples. We also analyzed PIN1 expression in combination with TP53 gene mutation and its correlation with the clinical outcome. In addition, we used synthetic small interfering RNA to silence PIN1 gene expression in TP53 wild-type and TP53 mutant HCC cell lines, and then evaluated cell proliferation, migration and invasion. Expression of PIN1 was strongly associated with expression of TP53 protein or TP53 mutation of HCC samples. PIN1 and TP53 expression in TP53 mutant HCC cell lines was higher than that in TP53 wild-type HCC cell lines. Silencing of PIN1 in HLE cells containing mutant TP53 significantly decreased cell proliferation, migration and invasion. In contrast to PIN1 silencing in HLE cells, PIN1 silencing in HepG2 cells containing functional wild-type TP53 resulted in enhanced tumor cell proliferation. HCC patients bearing PIN1 expression with wild-type TP53 were predicted to demonstrate favorable relapse-free survival. Our results suggest that PIN1 plays a role in cancer cell proliferation, migration and invasion in a different manner according to the TP53 gene mutation status in HCC. In particular, interaction of PIN1 with mutant TP53 can act as a tumor promoter and increase its oncogenic activities in HCC.

  19. Systems-level analysis of the regulation and function of p53 dynamics in cancer (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.

  20. Chromium(VI) transport and fate in unsaturated zone and aquifer: 3D Sandbox results. (United States)

    Zhao, Xingmin; Sobecky, Patricia A; Zhao, Lanpo; Crawford, Patrice; Li, Mingtang


    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).

  1. 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.


    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

  2. STS-53 Launch and Landing (United States)


    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. 75 FR 67100 - Superalloy Degassed Chromium From Japan (United States)


    ... 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...

  4. 76 FR 8773 - Superalloy Degassed Chromium From Japan (United States)


    ... 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,...

  5. Effects of chromium picolinate supplementation in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Niladê Rosinski Rocha


    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.

  6. Cobalt chromium stents versus stainless steel stents in diabetic patients

    Directory of Open Access Journals (Sweden)

    Mahmoud Ahmed Tantawy


    Conclusions: We concluded that no significant statistical difference was found between the two stents (cobalt-chromium alloy bare metal stent versus conventional bare metal stainless steel stent in diabetic patients regarding (initial procedural success, in-hospital complications, the incidence of ISR at follow up, event-free survival at follow up.

  7. Intestinal absorption of chromium as affected by wheat bran

    Energy Technology Data Exchange (ETDEWEB)

    Keim, K.S.; Holloway, C.L.; Hegsted, M.


    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 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.

  8. Domestic Production Issues in Chromium and Platinum-Group Metals (United States)


    Protection Agency. OPA 87-005. Washington: Government Printing Office, May 1987. 16. Foley, Jeffrey Y. and James C. Barker . Chromite Deposits Along...Mining, Metallurgical, and Petroleum Engineers, 1976. 52. Stowe, Clive W. Evolution of Chromium Ore Fields. New York: Van Nostrand Reinhold Company

  9. Spin-wave and critical neutron scattering from chromium

    DEFF Research Database (Denmark)

    Als-Nielsen, Jens Aage; Axe, J.D.; Shirane, G.


    Chromium and its dilute alloys are unique examples of magnetism caused by itinerant electrons. The magnetic excitations have been studied by inelastic neutron scattering using a high-resolution triple-axis spectrometer. Spin-wave peaks in q scans at constant energy transfer ℏω could, in general, ...

  10. New alloys to conserve critical elements. [replacing chromium in steels (United States)

    Stephens, J. R.


    Previous studies and surveys on availability of domestic reserves have shown that chromium is a most critical element within the U.S. metal industry. More precisely, the bulk of chromium is consumed in the production of stainless steels, specifically Type 304 stainless steel (304SS) which contains 18% Cr. The present paper deals with means of reducing chromium in commercial stainless steels by substituting more abundant or less expensive elements with the intent of maintaining the properties of 304SS. The discussion focuses on some of the oxidation and corrosion properties of new substitute stainless steels with only 12% Cr, which represents a potential saving of 33% of the chromium consumed in the production of 304SS. The alloying elements substituted for Cr in 304SS are selected according to their potential for protective oxide formation during high-temperature oxidation; these are Al, Si, Ti, Y, and misch metal which is 99.7% rare-earth metals containing 50 to 55% cerium. Other alloying elements to impart corrosion resistance are Mn, Mo, and V.

  11. Microbial biotechnology for remediation of aquatic habitats polluted with chromium

    Directory of Open Access Journals (Sweden)

    Viorica Coşier


    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.

  12. Oxidation resistant, thoria-dispersed nickel-chromium-aluminum alloy (United States)

    Baranow, S.; Klingler, L. J.


    Modified thoria-dispersed nickel-chromium alloy has been developed that exhibits greatly improved resistance to high-temperature oxidation. Additions of aluminum have been made to change nature of protective oxide scale entirely and to essentially inhibit oxidation at temperatures up to 1260 C.


    Directory of Open Access Journals (Sweden)

    Aniruddha Roy


    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.


    Directory of Open Access Journals (Sweden)

    V. V. Netrebko


    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.

  15. 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


    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.

  16. Preparation and Characterization of Plasma-Sprayed Ultrafine Chromium Oxide Coatings

    Institute of Scientific and Technical Information of China (English)

    LIN Feng; JIANG Xianliang; YU Yueguang; ZENG Keli; REN Xianjing; LI Zhenduo


    Ultrafine chromium oxide coatings were prepared by plasma spraying with ultrafine feedstock. Processing parameters of plasma spraying were optimized. Optical microscope (OM) was used to observe the microstructure of the ultrafine chromium oxide coatings. Scanning electron microscopy (SEM) was used to observe the morphology and particle size of ultrafine powder feedstock as well as to examine the microstructure of the chromium oxide coating. In addition, hardness and bonding strength of the ultrafine chromium oxide coatings were measured.The results showed that the optimized plasma spraying parameters were suitable for ultrafine chromium oxide coating and the properties and microstructure of the optimized ultrafine chromium oxide coating were superior compared to conventional chromium oxide wear resistant coatings.

  17. Investigations on the fracture toughness of austempered ductile iron alloyed with chromium

    Energy Technology Data Exchange (ETDEWEB)

    Rao, P. Prasad; Putatunda, Susil K


    An investigation was carried out to examine the influence of chromium content on the plane strain fracture toughness of austempered ductile iron (ADI). ADIs containing 0, 0.3 and 0.5 wt.% chromium were austempered over a range of temperatures to produce different microstructures. The microstructures were characterized by optical microscopy and X-ray diffraction. Plane strain fracture toughness of all these materials was determined and correlated with microstructure and chromium content. The chromium content was found to influence the fracture toughness through its influence on the processing window. Since the chromium addition shifts the processing window to shorter durations, the higher chromium alloys at higher austempering temperatures tend to fall outside of the processing window, resulting in less than optimum microstructure and inferior fracture toughness. A small chromium addition of 0.3 wt.% was found to be beneficial for the fracture toughness of ADI.

  18. Ailanthus Altissima and Phragmites Australis for chromium removal from a contaminated soil. (United States)

    Ranieri, Ezio; Fratino, Umberto; Petrella, Andrea; Torretta, Vincenzo; Rada, Elena Cristina


    The comparative effectiveness for hexavalent chromium removal from irrigation water, using two selected plant species (Phragmites australis and Ailanthus altissima) planted in soil contaminated with hexavalent chromium, has been studied in the present work. Total chromium removal from water was ranging from 55 % (Phragmites) to 61 % (Ailanthus). After 360 days, the contaminated soil dropped from 70 (initial) to 36 and 41 mg Cr/kg (dry soil), for Phragmites and Ailanthus, respectively. Phragmites accumulated the highest amount of chromium in the roots (1910 mg Cr/kg(dry tissue)), compared with 358 mg Cr/kg(dry tissue) for Ailanthus roots. Most of chromium was found in trivalent form in all plant tissues. Ailanthus had the lowest affinity for Cr(VI) reduction in the root tissues. Phragmites indicated the highest chromium translocation potential, from roots to stems. Both plant species showed good potentialities to be used in phytoremediation installations for chromium removal.

  19. 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


    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.

  20. Laboratory scale studies on removal of chromium from industrial wastes

    Institute of Scientific and Technical Information of China (English)


    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.

  1. Arsenic and chromium topsoil levels and cancer mortality in Spain. (United States)

    Núñez, Olivier; Fernández-Navarro, Pablo; Martín-Méndez, Iván; Bel-Lan, Alejandro; Locutura, Juan F; López-Abente, Gonzalo


    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.

  2. 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


    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.

  3. 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;


    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...

  4. Raman spectroscopy of supported chromium oxide catalysts : determination of chromium-oxygen bond distances and bond orders

    NARCIS (Netherlands)

    Weckhuysen, B.M.; Wachs, I.E.


    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

  5. Wild-type p53 binds to MYC promoter G-quadruplex (United States)

    Petr, Marek; Helma, Robert; Polášková, Alena; Krejčí, Aneta; Dvořáková, Zuzana; Kejnovská, Iva; Navrátilová, Lucie; Adámik, Matej; Vorlíčková, Michaela; Brázdová, Marie


    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

  6. ID4 regulates transcriptional activity of wild type and mutant p53 via K373 acetylation. (United States)

    Morton, Derrick J; Patel, Divya; Joshi, Jugal; Hunt, Aisha; Knowell, Ashley E; Chaudhary, Jaideep


    Given that mutated p53 (50% of all human cancers) is over-expressed in many cancers, restoration of mutant p53 to its wild type biological function has been sought after as cancer therapy. The conformational flexibility has allowed to restore the normal biological function of mutant p53 by short peptides and small molecule compounds. Recently, studies have focused on physiological mechanisms such as acetylation of lysine residues to rescue the wild type activity of mutant p53. Using p53 null prostate cancer cell line we show that ID4 dependent acetylation promotes mutant p53 DNA-binding capabilities to its wild type consensus sequence, thus regulating p53-dependent target genes leading to subsequent cell cycle arrest and apoptosis. Specifically, by using wild type, mutant (P223L, V274F, R175H, R273H), acetylation mimics (K320Q and K373Q) and non-acetylation mimics (K320R and K373R) of p53, we identify that ID4 promotes acetylation of K373 and to a lesser extent K320, in turn restoring p53-dependent biological activities. Together, our data provides a molecular understanding of ID4 dependent acetylation that suggests a strategy of enhancing p53 acetylation at sites K373 and K320 that may serve as a viable mechanism of physiological restoration of mutant p53 to its wild type biological function.

  7. Wild-type p53 binds to MYC promoter G-quadruplex. (United States)

    Petr, Marek; Helma, Robert; Polášková, Alena; Krejčí, Aneta; Dvořáková, Zuzana; Kejnovská, Iva; Navrátilová, Lucie; Adámik, Matej; Vorlíčková, Michaela; Brázdová, Marie


    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.

  8. 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


    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....

  9. [TP53 mutations and molecular epidemiology]. (United States)

    Otsuka, Kazunori; Ishioka, Chikashi


    Tumor suppressor p53 protein is activated by a variety of cellular stresses through several pathways and transactivates its downstream genes, including regulators of cell cycle, apoptosis and DNA repair. The loss of p53 function by TP53 gene mutations therefore fails to activate these genes and is thought to be a critical cause of carcinogenesis and/or tumor progression. TP53 is one of the most frequently mutated genes in human cancer. TP53 mutations are found in about 50% of human cancers, although the frequency of TP53 mutations differs among tumor types. However, the degree of functional disorder of mutant p53 varies according to the type of TP53 mutation. And the effects of p53 on cancer formation and/or progression are influenced by the degree of p53 dysfunction. So it is important to analyze the effects of TP53 mutations carefully according to the oncogenicity of each mutation from the molecular epidemiological point of view. Here, together with some cautions needed for analyzing and interpreting the significance of TP53 gene mutations, we present some examples of the identified specific mutation spectrum and the correlation between the prognosis and TP53 mutation in some cancers.

  10. 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


    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

  11. p53 gene mutations, p53 protein accumulation and compartmentalization in colorectal adenocarcinoma.



    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...

  12. Conversion of Fibroblasts to Neural Cells by p53 Depletion

    Directory of Open Access Journals (Sweden)

    Di Zhou


    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.

  13. A computational investigation of boron-doped chromium and chromium clusters by density functional theory

    Institute of Scientific and Technical Information of China (English)


    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.

  14. 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


    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.

  15. 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


    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.)

  16. Chromium(VI) but not chromium(III) species decrease mitoxantrone affinity to DNA. (United States)

    Nowicka, Anna M; Stojek, Zbigniew; Hepel, Maria


    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.

  17. Hot Corrosion Behavior of High-Chromium, High-Carbon Cast Irons in NaCl-KCl Molten Salts

    Directory of Open Access Journals (Sweden)

    S. Vuelvas-Rayo


    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.

  18. Chromium isotopes in carbonates — A tracer for climate change and for reconstructing the redox state of ancient seawater

    DEFF Research Database (Denmark)

    Frei, Robert; Gaucher, Claudio; Døssing, Lasse Nørbye


    Strontium and carbon isotopes of marine carbonates are routinely applied for chemostratigraphic cross correlations of time-equivalent sedimentary sequences and for calibration of the compositional evolution of seawater throughout Earth's history, mainly for the purpose of reconstructing ancient.......708, and lower 147Sm/144Nd values of ~0.11, a source which is strongly affected by continentally derived input. Chromium isotopes provide a powerful tool for reconstructing the redox state of ancient seawater since positive values indicate that, at least locally, Neoproterozoic shallow ocean waters were......, glaciation acts as an amplifier of d53Cr signals. These signals in marine carbonates are a sensitive tracer for redox processes in the ocean and/or on land and have the potential to contribute significantly, in combination with the other commonly used isotopic tracers, to the reconstruction of climatic...

  19. Maximum availability and mineralogical control of chromium released from AOD slag. (United States)

    Li, Junguo; Liu, Bao; Zeng, Yanan; Wang, Ziming; Gao, Zhiyuan


    AOD (argon oxygen decarburization) slag is the by-product in the stainless steel refining process. Chromium existing in AOD slag can leach out and probably poses a serious threat to the environment. To assess the leaching toxicity of chromium released from AOD slag, the temperature-dependent maximum availability leaching test was performed. To determine the controlling mineralogical phases of chromium released from AOD slag, a Visual MINTEQ simulation was established based on Vminteq30 and the FactSage 7.0 database. The leaching tests indicated that the leaching availability of chromium was slight and mainly consisted of trivalent chromium. Aging of AOD slag under the atmosphere can oxidize trivalent chromium to hexavalent chromium, which could be leached out by rainwater. According to the simulation, the chromium concentration in leachates was controlled by the freely soluble pseudo-binary phases in the pH = 7.0 leaching process and controlled by the Cr2O3 phase in the pH = 4.0 leaching process. Chromium concentrations were underestimated when the controlling phases were determined to be FeCr2O4 and MgCr2O4. Facilitating the generation of the insoluble spinel-like phases during the cooling and disposal process of the molten slag could be an effective approach to decreasing the leaching concentration of chromium and its environmental risk.

  20. Finished leather waste chromium acid extraction and anaerobic biodegradation of the products. (United States)

    Ferreira, Maria J; Almeida, Manuel F; Pinho, Sílvia C; Santos, Isabel C


    Due to the amounts of chromium in the leachate resulting from leather leaching tests, chromium sulfate tanned leather wastes are very often considered hazardous wastes. To overcome this problem, one option could be recovering the chromium and, consequently, lowering its content in the leather scrap. With this objective, chromium leather scrap was leached with sulfuric acid solutions at low temperature also aiming at maximizing chromium removal with minimum attack of the leather matrix. The effects of leather scrap dimension, sulfuric acid and sodium sulfate concentration in the solutions, as well as extraction time and temperature on chromium recovery were studied, and, additionally, organic matrix degradation was evaluated. The best conditions found for chromium recovery were leather scrap conditioning using 25mL of concentrated H(2)SO(4)/L solution at 293 or 313K during 3 or 6days. Under such conditions, 30-60+/-5% of chromium was recovered and as low as 3-6+/-1% of the leather total organic carbon (TOC) was dissolved. Using such treatment, the leather scrap area and volume are reduced and the residue is a more brittle material showing enhanced anaerobic biodegradability. Although good recovery results were achieved, due to the fact that the amount of chromium in eluate exceeded the threshold value this waste was still hazardous. Thus, it needs to be methodically washed in order to remove all the chromium de-linked from collagen.

  1. Revisiting p53 for cancer-specific chemo- and radiotherapy: ten years after. (United States)

    Beckta, Jason M; Ahmad, Syed Farhan; Yang, Hu; Valerie, Kristoffer


    Despite intense studies, highly effective therapeutic strategies against cancer have not yet been fully exploited, because few true cancer-specific targets have been identified. Most modalities, perhaps with the exception of radiation therapy, target proliferating cells, which are also abundant in normal tissues. Thus, most current cancer treatments have significant side effects. More than 10 years ago, the tumor suppressor p53 was first explored as a cancer-specific target. At the time, the approach was to introduce a normal p53 gene into mutant p53 (mp53) tumor cells to induce cell cycle arrest and apoptosis. However, this strategy did not hold up and mostly failed in subsequent clinical studies. Recent research developments have now returned p53 to the limelight. Several studies have reported that mutant or null p53 tumor cells undergo apoptosis more easily than genetically matched, normal p53 counterparts when inhibiting a specific stress kinase in combination with standard chemotherapy or when exposed to an ataxia-telangiectasia mutated (ATM) kinase inhibitor and radiation, thus achieving true cancer specificity in animal tumor models. This short review highlights several of these recent studies, discusses possible mechanism(s) for mp53-mediated "synthetic lethality," and the implications for cancer therapy.

  2. Black and green pigments based on chromium-cobalt spinels

    Energy Technology Data Exchange (ETDEWEB)

    Eliziario, Sayonara A., E-mail: [Departamento de Fisico-Quimica, Instituto de Quimica, UNESP - Univ Estadual Paulista, Araraquara, SP (Brazil); Departamento de Quimica, CCEN, Universidade Federal da Paraiba, Campus I, Joao Pessoa, PB (Brazil); Andrade, Jeferson M. de [Departamento de Quimica, CCEN, Universidade Federal da Paraiba, Campus I, Joao Pessoa, PB (Brazil); Lima, Severino J.G. [Departamento de Engenharia Mecanica, CT, Universidade Federal da Paraiba, Campus I, Joao Pessoa, PB (Brazil); Paskocimas, Carlos A. [Universidade Federal do Rio Grande do Norte, CT, Natal, RN (Brazil); Soledade, Luiz E.B. [Departamento de Quimica, CCEN, Universidade Federal da Paraiba, Campus I, Joao Pessoa, PB (Brazil); Hammer, P.; Longo, E. [Departamento de Fisico-Quimica, Instituto de Quimica, UNESP - Univ Estadual Paulista, Araraquara, SP (Brazil); Souza, Antonio G.; Santos, Ieda M.G. [Departamento de Quimica, CCEN, Universidade Federal da Paraiba, Campus I, Joao Pessoa, PB (Brazil)


    Highlights: {yields} Co(Co{sub 2-x}Cr{sub x})O{sub 4} powders with different chromium concentrations (x = 0, 0.25 and 1) were prepared by the polymeric precursor method. {yields} Co(CoCr)O{sub 4} and Co(Co{sub 1.75}Cr{sub 0.25})O{sub 4} displayed a dark color and CoCr{sub 2}O{sub 4} was green. {yields} The colors were related to the different oxidation states of Cr and Co. {yields} Cobalt enrichment result in an increasing presence of Co(III) and a decrease amount of Cr(VI). - Abstract: Chromium and cobalt oxides are widely used in the manufacture of industrial pigments. In this work, the Co(Co{sub 2-x}Cr{sub x})O{sub 4} powders with different chromium concentrations (x = 0, 0.25 and 1) were synthesized by the polymeric precursor method, heat treatment between 600 and 1000 deg. C. These powders were characterized by X-ray diffraction, infrared spectroscopy, colorimetry, UV-vis absorption and X-ray photoelectron spectroscopies. Even with the addition of chromium, the XRD patterns revealed that all powders crystallize in a single spinel cubic structure. The spinels with higher cobalt amount, Co(CoCr)O{sub 4} and Co(Co{sub 1.75}Cr{sub 0.25})O{sub 4}, displayed a dark color, without the Co{sup 3+} reduction observed in Co{sub 3}O{sub 4} between 900 and 950 deg. C. The spinel with higher chromium amount, CoCr{sub 2}O{sub 4}, was green. The colors were directly related to the occupation of tetrahedral and octahedral sites by the chromophores, as well as to the different oxidation states of chromium and cobalt. The different optical band gap values estimated from UV-vis spectra suggested the existence of intermediary energy levels within the band gap. X-ray photoelectron spectroscopy confirmed an increasing presence of Co(III) and a decreasing amount of Cr(VI) with cobalt enrichment.

  3. 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.

  4. 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


    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.

  5. Pharmacological reactivation of p53 as a strategy to treat cancer. (United States)

    Zawacka-Pankau, J; Selivanova, G


    It has been confirmed through studies using the technique of unbiased sequencing that the TP53 tumour suppressor is the most frequently inactivated gene in cancer. This finding, together with results from earlier studies, provides compelling evidence for the idea that p53 ablation is required for the development and maintenance of tumours. Genetic reconstitution of the function of p53 leads to the suppression of established tumours as shown in mouse models. This strongly supports the notion that p53 reactivation by small molecules could provide an efficient strategy to treat cancer. In this review, we summarize recent advances in the development of small molecules that restore the function of mutant p53 by different mechanisms, including stabilization of its folding by Apr-246, which is currently being tested in a Phase II clinical trial. We discuss several classes of compounds that reactivate wild-type p53, such as Mdm2 inhibitors, which are currently undergoing clinical testing, MdmX inhibitors and molecules targeting factors upstream of Mdm2/X or p53 itself. Finally, we consider the clinical applications of compounds targeting p53 and the p53 pathway.

  6. p53 mediates the suppression of cancer cell invasion by inducing LIMA1/EPLIN. (United States)

    Ohashi, Tomoko; Idogawa, Masashi; Sasaki, Yasushi; Tokino, Takashi


    The tumor suppressor gene p53 is frequently mutated in human cancer. p53 executes various functions, such as apoptosis induction and cell cycle arrest, by modulating transcriptional regulation. In this study, LIM domain and Actin-binding protein 1 (LIMA1) was identified as a target of the p53 family using a cDNA microarray. We also evaluated genome-wide occupancy of the p53 protein by performing chromatin immunoprecipitation-sequencing (ChIP-seq) and identified two p53 response elements in the LIMA1 gene. LIMA1 protein levels were increased by treatment with nutlin-3a, a small molecule that activates endogenous p53. In addition, LIMA1 expression was significantly downregulated in cancers compared with normal tissues. Knockdown of LIMA1 significantly enhanced cancer cell invasion and partially inhibited p53-induced suppression of cell invasion. Furthermore, low expression of LIMA1 in cancer patients correlated with decreased survival and poor prognosis. Thus, p53-induced LIMA1 inhibits cell invasion, and the downregulation of LIMA1 caused by p53 mutation results in decreased survival in cancer patients. Collectively, this study reveals the molecular mechanism of LIMA1 downregulation in various cancers and suggests that LIMA1 may be a novel prognostic predictor and a therapeutic target for cancer.

  7. Pharmacological activation of wild-type p53 in the therapy of leukemia. (United States)

    Kojima, Kensuke; Ishizawa, Jo; Andreeff, Michael


    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.

  8. Chromium Isotopic Fractionation During Biogeochemical Cr (IV) Reduction in Hanford Sediment Column Experiments with Native Aquifer Microbial Communities (United States)

    Qin, L.; Christensen, J. N.; Brown, S. T.; Yang, L.; Conrad, M. E.; Sonnenthal, E. L.; Beller, H. R.


    Hexavalent Chromium contamination in groundwater within the DOE complex, including the Hanford 100D and 100H sites has been a long-standing issue. It has been established that certain bacteria (including denitrifying and sulfate-reducing bacteria) harbor enzymes that catalyze Cr(VI) reduction to relatively nontoxic Cr(III). Microbial reduction of Cr(VI) also occurs indirectly by products of microbial respiration, such as sulfide and Fe(II). Chromium isotopes can be fractionated during Cr(VI) reduction and provides a potential basis for characterizing and discriminating between different microbial metabolic and geochemical pathways associated with Cr(VI) reductive immobilization. Addition of electron donor to contaminated groundwater systems to create conditions favorable for reductive metal immobilization has become a widely utilized remediation practice. We conducted a series of small-scale column experiments with homogenized material from the Hanford 100H aquifer to examine the effects of differing electron acceptors on local microbial communities. All columns have a continuous inflow of solutions with constant concentrations of Cr(VI), lactate (electron donor), and the appropriate electron acceptor (e.g. nitrate or sulfate). The Cr isotopic composition in the effluent was measured using a 50-54 double-spike technique and a Triton TIMS. Cr concentration measurements showed that the greatest Cr(VI) reduction occurred in the sulfate columns. Our preliminary Cr isotopic data show that under these conditions the delta 53Cr value increased from close to 0 to 4 per mil while the Cr concentration decreased from 260 ppb to 30 ppb in the effluent. This yields an apparent fractionation factor of 0.9979 (2.1 per mil). A decrease in Cr concentration from 260 ppb to 190 ppb in a nitrate-reducing column was accompanied by an increase of 1 per mil in delta 53Cr. Further Cr isotopic data will be presented and the effects of differing flow rates and electron acceptors will be

  9. 7 CFR 982.53 - Substandard hazelnuts. (United States)


    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Substandard hazelnuts. 982.53 Section 982.53... Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE HAZELNUTS GROWN IN OREGON AND WASHINGTON Order Regulating Handling Control of Distribution § 982.53 Substandard hazelnuts. The Board...

  10. 47 CFR 53.211 - Audit planning. (United States)


    ... 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....

  11. 7 CFR 1794.53 - Environmental report. (United States)


    ... 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...

  12. 15 CFR 400.53 - Information. (United States)


    ... 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 request submission of any information, including business proprietary information, and written argument necessary...

  13. 14 CFR 63.53 - Knowledge requirements. (United States)


    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Knowledge requirements. 63.53 Section 63.53 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN CERTIFICATION: FLIGHT CREWMEMBERS OTHER THAN PILOTS Flight Navigators § 63.53 Knowledge requirements. (a)...

  14. 33 CFR 53.9 - Responsibilities. (United States)


    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Responsibilities. 53.9 Section 53.9 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PERSONNEL COAST GUARD WHISTLEBLOWER PROTECTION § 53.9 Responsibilities. (a) The Inspector General, Department of Homeland...

  15. 19 CFR 151.53 - Sample lockers. (United States)


    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Sample lockers. 151.53 Section 151.53 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY... Materials § 151.53 Sample lockers. A suitable place or containers shall be provided for the safekeeping...

  16. 29 CFR 1926.53 - Ionizing radiation. (United States)


    ... 29 Labor 8 2010-07-01 2010-07-01 false Ionizing radiation. 1926.53 Section 1926.53 Labor... § 1926.53 Ionizing radiation. (a) In construction and related activities involving the use of sources of ionizing radiation, the pertinent provisions of the Nuclear Regulatory Commission's Standards...

  17. 42 CFR 53.113 - Community service. (United States)


    ... 42 Public Health 1 2010-10-01 2010-10-01 false Community service. 53.113 Section 53.113 Public... To Pay; Community Service; Nondiscrimination. § 53.113 Community service. (a) Applicability. The... community service assurance. (b) Definitions. As used in this section: (1) The term community...

  18. 27 CFR 53.1 - Introduction. (United States)


    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Introduction. 53.1 Section... THE TREASURY (CONTINUED) FIREARMS MANUFACTURERS EXCISE TAXES-FIREARMS AND AMMUNITION Introduction § 53.1 Introduction. The regulations in this part (part 53, subchapter C, chapter I, title 27, Code...

  19. 14 CFR 1260.53 - Incremental funding. (United States)


    ... 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...

  20. 33 CFR 401.53 - Obstructing navigation. (United States)


    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Obstructing navigation. 401.53 Section 401.53 Navigation and Navigable Waters SAINT LAWRENCE SEAWAY DEVELOPMENT CORPORATION, DEPARTMENT OF TRANSPORTATION SEAWAY REGULATIONS AND RULES Regulations Seaway Navigation § 401.53...

  1. 7 CFR 550.53 - Financial reporting. (United States)


    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Financial reporting. 550.53 Section 550.53 Agriculture... Reports and Records § 550.53 Financial reporting. Financial Status Report. (a) Each REE Agency shall.... A financial status report shall consist of the following information: (1) The name and address...

  2. 14 CFR 460.53 - Security. (United States)


    ... 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...

  3. 28 CFR 32.53 - Review. (United States)


    ... 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—...

  4. 29 CFR 1918.53 - Cargo winches. (United States)


    ... 29 Labor 7 2010-07-01 2010-07-01 false Cargo winches. 1918.53 Section 1918.53 Labor Regulations...) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Vessel's Cargo Handling Gear § 1918.53 Cargo winches. (a...) There shall be no load other than the fall and cargo hook assembly on the winch when changing gears on...

  5. 45 CFR 702.53 - Closed meetings. (United States)


    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Closed meetings. 702.53 Section 702.53 Public..., REPORTS, AND MEETINGS OF THE COMMISSION Meetings § 702.53 Closed meetings. (a) The Commission may close a portion or portions of a meeting and withhold information pertaining to such meeting when it...

  6. 47 CFR 53.209 - Biennial audit. (United States)


    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Biennial audit. 53.209 Section 53.209... PROVISIONS CONCERNING BELL OPERATING COMPANIES Separate Affiliate; Safeguards § 53.209 Biennial audit. (a) A... obtain and pay for a Federal/State joint audit every two years conducted by an independent auditor...

  7. 10 CFR 34.53 - Posting. (United States)


    ... 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...

  8. 32 CFR 643.53 - Consideration. (United States)


    ... 32 National Defense 4 2010-07-01 2010-07-01 true Consideration. 643.53 Section 643.53 National... Leases § 643.53 Consideration. (a) Unless otherwise authorized by this regulation or directed by the SA, the consideration for a lease of real estate will be the appraised fair market rental value....

  9. 14 CFR 23.53 - Takeoff performance. (United States)


    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Takeoff performance. 23.53 Section 23.53... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Flight Performance § 23.53 Takeoff performance. (a) For normal, utility, and acrobatic category airplanes, the takeoff distance must...

  10. 10 CFR 30.53 - Tests. (United States)


    ... 10 Energy 1 2010-01-01 2010-01-01 false Tests. 30.53 Section 30.53 Energy NUCLEAR REGULATORY..., Tests, and Reports § 30.53 Tests. Each licensee shall perform, or permit the Commission to perform, such tests as the Commission deems appropriate or necessary for the administration of the regulations in...

  11. Genome-wide analysis of the human p53 transcriptional network unveils a lncRNA tumour suppressor signature. (United States)

    Sánchez, Yolanda; Segura, Victor; Marín-Béjar, Oskar; Athie, Alejandro; Marchese, Francesco P; González, Jovanna; Bujanda, Luis; Guo, Shuling; Matheu, Ander; Huarte, Maite


    Despite the inarguable relevance of p53 in cancer, genome-wide studies relating endogenous p53 activity to the expression of lncRNAs in human cells are still missing. Here, by integrating RNA-seq with p53 ChIP-seq analyses of a human cancer cell line under DNA damage, we define a high-confidence set of 18 lncRNAs that are p53 transcriptional targets. We demonstrate that two of the p53-regulated lncRNAs are required for the efficient binding of p53 to some of its target genes, modulating the p53 transcriptional network and contributing to apoptosis induction by DNA damage. We also show that the expression of p53-lncRNAs is lowered in colorectal cancer samples, constituting a tumour suppressor signature with high diagnostic power. Thus, p53-regulated lncRNAs establish a positive regulatory feedback loop that enhances p53 tumour suppressor activity. Furthermore, the signature defined by p53-regulated lncRNAs supports their potential use in the clinic as biomarkers and therapeutic targets.

  12. Regulation of the p53 response and its relationship to cancer. (United States)

    Meek, David W


    p53 has been studied intensively as a major tumour suppressor that detects oncogenic events in cancer cells and eliminates them through senescence (a permanent non-proliferative state) or apoptosis. Consistent with this role, p53 activity is compromised in a high proportion of all cancer types, either through mutation of the TP53 gene (encoding p53) or changes in the status of p53 modulators. p53 has additional roles, which may overlap with its tumour-suppressive capacity, in processes including the DNA damage response, metabolism, aging, stem cell differentiation and fertility. Moreover, many mutant p53 proteins, termed 'gain-of-function' (GOF), acquire new activities that help drive cancer aggression. p53 is regulated mainly through protein turnover and operates within a negative-feedback loop with its transcriptional target, MDM2 (murine double minute 2), an E3 ubiquitin ligase which mediates the ubiquitylation and proteasomal degradation of p53. Induction of p53 is achieved largely through uncoupling the p53-MDM2 interaction, leading to elevated p53 levels. Various stress stimuli acting on p53 (such as hyperproliferation and DNA damage) use different, but overlapping, mechanisms to achieve this. Additionally, p53 activity is regulated through critical context-specific or fine-tuning events, mediated primarily through post-translational mechanisms, particularly multi-site phosphorylation and acetylation. In the present review, I broadly examine these events, highlighting their regulatory contributions, their ability to integrate signals from cellular events towards providing most appropriate response to stress conditions and their importance for tumour suppression. These are fascinating aspects of molecular oncology that hold the key to understanding the molecular pathology of cancer and the routes by which it may be tackled therapeutically.

  13. Uncovering the role of p53 splice variants in human malignancy: a clinical perspective

    Directory of Open Access Journals (Sweden)

    Surget S


    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

  14. Gene p53 mutations, protein p53, and anti-p53 antibodies as biomarkers of cancer process. (United States)

    Lutz, Waldemar; Nowakowska-Swirta, Ewa


    The finding that gene mutations and changes in their expression form the basis of cancer processes, has prompted molecular epidemiologists to use biomarkers for detecting damaged genes or proteins synthesized under their control in easily available cellular material or systemic liquids. Mutations in the suppressor gen p53 are thought to be essential for cancer development. This gen is one of the most important regulators of transcription, cellular cycle, DNA repair and apoptosis detected till now. Inactivation of gene p53 leads to uncontrolled cell divisions, and further to transformation of normal cells into the carcinous ones. Observations that mutations in gene p53 appear under conditions of occupational and environmental exposures to chemical and physical carcinogens, such as vinyl chloride, radon, or aflatoxin B1, have proved to be of enormous importance for the occupational and environmental health. Changes in expression of gene p53, and also its mutations, cause variations of cellular protein p53 concentration. Higher cellular protein p53 levels are associated with increased protein transfer to the extracellular liquid and to blood. It has been observed that increased blood serum protein p53 concentrations may have a prognostic value in early diagnosis of lung cancer. The results of a number of studies confirm that accumulation of a mutated form of protein p53, and presumably also large quantities of wild forms of that protein in the cells, may be a factor that triggers the production of anti-p53 antibodies. Statistical analysis showed that anti-p53 antibodies can be regarded as a specific biomarker of cancer process. The prevalence of anti-p53 antibodies correlated with the degree of cancer malignancy. The increased incidence of anti-p53 antibodies was also associated with higher frequency of mutations in gene p53. There are some reports confirming that anti-p53 antibodies emerging in blood serum in the subclinical phase of cancer development may be

  15. Gene Expression Profiling Identifies Important Genes Affected by R2 Compound Disrupting FAK and P53 Complex

    Directory of Open Access Journals (Sweden)

    Vita M. Golubovskaya


    Full Text Available Focal Adhesion Kinase (FAK is a non-receptor kinase that plays an important role in many cellular processes: adhesion, proliferation, invasion, angiogenesis, metastasis and survival. Recently, we have shown that Roslin 2 or R2 (1-benzyl-15,3,5,7-tetraazatricyclo[,7~]decane compound disrupts FAK and p53 proteins, activates p53 transcriptional activity, and blocks tumor growth. In this report we performed a microarray gene expression analysis of R2-treated HCT116 p53+/+ and p53−/− cells and detected 1484 genes that were significantly up- or down-regulated (p < 0.05 in HCT116 p53+/+ cells but not in p53−/− cells. Among up-regulated genes in HCT p53+/+ cells we detected critical p53 targets: Mdm-2, Noxa-1, and RIP1. Among down-regulated genes, Met, PLK2, KIF14, BIRC2 and other genes were identified. In addition, a combination of R2 compound with M13 compound that disrupts FAK and Mmd-2 complex or R2 and Nutlin-1 that disrupts Mdm-2 and p53 decreased clonogenicity of HCT116 p53+/+ colon cancer cells more significantly than each agent alone in a p53-dependent manner. Thus, the report detects gene expression profile in response to R2 treatment and demonstrates that the combination of drugs targeting FAK, Mdm-2, and p53 can be a novel therapy approach.

  16. Removal of Chromium with The Complexing Agents from Industrial Effluents

    Directory of Open Access Journals (Sweden)

    J. L. Prameena Sheeja


    Full Text Available Human activities and consequent developments have brought about the spectre of an overwhelming degradation of all facets of the natural environment-physical, chemical, biological and social. Environmental pollution, especially by chemicals, is one of the most significant factors in the degradation of the biosphere components. Among all chemical contaminants, heavy metals are believed to be of special ecological, biological and health significance. Unlike organic pollutants, the majority of which are susceptible to biological degradation, metal ions do not degrade into harmless end products. Chemical precipitation is a simple and economical method, and hence, has been widely used. The reduction of chromium (VI to chromium (III can be done with the help of ferrous sulphate. The precipitation was carried out in the presence and absence of complexing agents such as ammonium chloride, tartrate and citrate.

  17. Internal Friction In The PFN Ceramics With Chromium Dopand


    Zachariasz R.; Bochenek D.; Bruś B.


    An aim of this work was to determine an influence of an admixture, the chromium (for x from 0.01 to 0.06), on the mechanical properties of the PFN ceramics. The ceramics with chemical composition Pb(Fe0.5−xCrxNb0.5)O3 was synthesized in two steps from simple oxides PbO, Fe2O3, Nb2O5, Cr2O3. The first stage was based on obtaining the FeNbO4 from the Fe2O3 and Nb2O5 simple oxides. At this stage an admixture in a form the Cr2O3 chromium oxide was added to the solution. In the second stage the Pb...

  18. Tumor suppressor protein C53 antagonizes checkpoint kinases to promote cyclin-dependent kinase 1 activation. (United States)

    Jiang, Hai; Wu, Jianchun; He, Chen; Yang, Wending; Li, Honglin


    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-kappaB 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 Cdk1 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 Chk1 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.

  19. 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


    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.

  20. Immunomodulatory Function of the Tumor Suppressor p53 in Host Immune Response and the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Yan Cui


    Full Text Available The tumor suppressor p53 is the most frequently mutated gene in human cancers. Most of the mutations are missense leading to loss of p53 function in inducing apoptosis and senescence. In addition to these autonomous effects of p53 inactivation/dysfunction on tumorigenesis, compelling evidence suggests that p53 mutation/inactivation also leads to gain-of-function or activation of non-autonomous pathways, which either directly or indirectly promote tumorigenesis. Experimental and clinical results suggest that p53 dysfunction fuels pro-tumor inflammation and serves as an immunological gain-of-function driver of tumorigenesis via skewing immune landscape of the tumor microenvironment (TME. It is now increasingly appreciated that p53 dysfunction in various cellular compartments of the TME leads to immunosuppression and immune evasion. Although our understanding of the cellular and molecular processes that link p53 activity to host immune regulation is still incomplete, it is clear that activating/reactivating the p53 pathway in the TME also represents a compelling immunological strategy to reverse immunosuppression and enhance antitumor immunity. Here, we review our current understanding of the potential cellular and molecular mechanisms by which p53 participates in immune regulation and discuss how targeting the p53 pathway can be exploited to alter the immunological landscape of tumors for maximizing therapeutic outcome.

  1. Immunomodulatory Function of the Tumor Suppressor p53 in Host Immune Response and the Tumor Microenvironment (United States)

    Cui, Yan; Guo, Gang


    The tumor suppressor p53 is the most frequently mutated gene in human cancers. Most of the mutations are missense leading to loss of p53 function in inducing apoptosis and senescence. In addition to these autonomous effects of p53 inactivation/dysfunction on tumorigenesis, compelling evidence suggests that p53 mutation/inactivation also leads to gain-of-function or activation of non-autonomous pathways, which either directly or indirectly promote tumorigenesis. Experimental and clinical results suggest that p53 dysfunction fuels pro-tumor inflammation and serves as an immunological gain-of-function driver of tumorigenesis via skewing immune landscape of the tumor microenvironment (TME). It is now increasingly appreciated that p53 dysfunction in various cellular compartments of the TME leads to immunosuppression and immune evasion. Although our understanding of the cellular and molecular processes that link p53 activity to host immune regulation is still incomplete, it is clear that activating/reactivating the p53 pathway in the TME also represents a compelling immunological strategy to reverse immunosuppression and enhance antitumor immunity. Here, we review our current understanding of the potential cellular and molecular mechanisms by which p53 participates in immune regulation and discuss how targeting the p53 pathway can be exploited to alter the immunological landscape of tumors for maximizing therapeutic outcome. PMID:27869779

  2. JMJD6 promotes colon carcinogenesis through negative regulation of p53 by hydroxylation.

    Directory of Open Access Journals (Sweden)

    Feng Wang


    Full Text Available Jumonji domain-containing 6 (JMJD6 is a member of the Jumonji C domain-containing family of proteins. Compared to other members of the family, the cellular activity of JMJD6 is still not clearly defined and its biological function is still largely unexplored. Here we report that JMJD6 is physically associated with the tumor suppressor p53. We demonstrated that JMJD6 acts as an α-ketoglutarate- and Fe(II-dependent lysyl hydroxylase to catalyze p53 hydroxylation. We found that p53 indeed exists as a hydroxylated protein in vivo and that the hydroxylation occurs mainly on lysine 382 of p53. We showed that JMJD6 antagonizes p53 acetylation, promotes the association of p53 with its negative regulator MDMX, and represses transcriptional activity of p53. Depletion of JMJD6 enhances p53 transcriptional activity, arrests cells in the G1 phase, promotes cell apoptosis, and sensitizes cells to DNA damaging agent-induced cell death. Importantly, knockdown of JMJD6 represses p53-dependent colon cell proliferation and tumorigenesis in vivo, and significantly, the expression of JMJD6 is markedly up-regulated in various types of human cancer especially in colon cancer, and high nuclear JMJD6 protein is strongly correlated with aggressive clinical behaviors of colon adenocarcinomas. Our results reveal a novel posttranslational modification for p53 and support the pursuit of JMJD6 as a potential biomarker for colon cancer aggressiveness and a potential target for colon cancer intervention.

  3. Immunomodulatory Function of the Tumor Suppressor p53 in Host Immune Response and the Tumor Microenvironment. (United States)

    Cui, Yan; Guo, Gang


    The tumor suppressor p53 is the most frequently mutated gene in human cancers. Most of the mutations are missense leading to loss of p53 function in inducing apoptosis and senescence. In addition to these autonomous effects of p53 inactivation/dysfunction on tumorigenesis, compelling evidence suggests that p53 mutation/inactivation also leads to gain-of-function or activation of non-autonomous pathways, which either directly or indirectly promote tumorigenesis. Experimental and clinical results suggest that p53 dysfunction fuels pro-tumor inflammation and serves as an immunological gain-of-function driver of tumorigenesis via skewing immune landscape of the tumor microenvironment (TME). It is now increasingly appreciated that p53 dysfunction in various cellular compartments of the TME leads to immunosuppression and immune evasion. Although our understanding of the cellular and molecular processes that link p53 activity to host immune regulation is still incomplete, it is clear that activating/reactivating the p53 pathway in the TME also represents a compelling immunological strategy to reverse immunosuppression and enhance antitumor immunity. Here, we review our current understanding of the potential cellular and molecular mechanisms by which p53 participates in immune regulation and discuss how targeting the p53 pathway can be exploited to alter the immunological landscape of tumors for maximizing therapeutic outcome.

  4. Genistein induces apoptosis by stabilizing intracellular p53 protein through an APE1-mediated pathway. (United States)

    Zhu, Jianwu; Zhang, Chong; Qing, Yi; Cheng, Yi; Jiang, Xiaolin; Li, Mengxia; Yang, Zhenzhou; Wang, Dong


    Genistein (GEN) has been previously shown to have a proapoptotic effect on cancer cells through a p53-dependent pathway, the mechanism of which remains unclear. One of its intracellular targets, APE1, protects against apoptosis under genotoxic stress and interacts with p53. In this current study, we explored the mechanism of the proapoptotic effect of GEN by examining the APE1-p53 protein-protein interaction. We initially showed that the p53 protein level was elevated in GEN-treated human non-small lung cancer A549 cells and cervical cancer HeLa cells. By examining both protein synthesis and degradation, we found that GEN enhances p53 intracellular stability by interfering with the interaction of APE1 and p53, which provided a plausible explanation for how GEN initiates apoptosis. Furthermore, we found that the interaction between APE1 and p53 is important for the degradation of p53 and is dependent on the redox domain of APE1 by utilizing the redox domain mutant APE1 C65A. Our data suggest that the degradation of wild-type p53 is blocked when the redox domain of APE1 is masked or interrupted. Based on this evidence, we hereby report a novel mechanism of p53 degradation through an APE1-mediated, redox-dependent pathway.

  5. Interactions of the p53 protein family in cellular stress response in gastrointestinal tumors. (United States)

    Vilgelm, Anna E; Washington, Mary K; Wei, Jinxiong; Chen, Heidi; Prassolov, Vladimir S; Zaika, Alexander I


    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.

  6. Preparation of Silica Modified with 2-Mercaptoimidazole and its SorptionProperties of Chromium(III

    Directory of Open Access Journals (Sweden)

    Harry Budiman


    Full Text Available Modified silica gel was prepared to remove the heavy metal of chromium(III from water sample. Silica gel was used as supporting material and the 2-mercaptoimidazole was immobilized onto surface silica so that the silica would have selective properties to adsorb the heavy metal chromium(III through the formation of coordination compound between the 2-mercaptoimidazole and chromium(III. The characterization of modified silica gel was carried out by analyzing the Fourier Transform Infrared Spectrum of this material in order to ensure the immobilization of 2-mercaptoimidazole onto the surface. The effect of pH solution, initial concentration of chromium(III, and interaction time were investigated in batch mode to find the adsorption properties of chromium(III onto modified silica. The condition optimum of these parameters was applied to determine the removal percentage of chromium(III in water sample using the modified silica gel

  7. Determination of Chromium(III) Picolinate Using High Performance Liquid Chromatography-Ultraviolet Spectrophotometry

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Il; Woo, Dong Jin; Kang, Dae Kyung [EASY BIO System, Inc, Chonan (Korea, Republic of); Lee, Myung Hee [Pollin, Inc, Seoul (Korea, Republic of); Woo, Gun Jo [Korea Food and Drug Administration, Seoul (Korea, Republic of); Cha, Ki Won [Inha University, Incheon (Korea, Republic of)


    Cr-(pic){sub 3} has been widely used as food additives, drugs, and feed additives. Accordingly, its determination method should be established. In the present paper, we have studied the determination method of chromium(III) picolinate accurately using ESI-MS on-lined with HPLC. Chromium(III) picolinate in feed products was determined successfully. Chromium(III) is very well known as an essential mineral. It is suggested as a cofactor in the maintenance of both normal lipid and carbohydrate metabolism by assisting the action of insulin on a cell membrane. According to the National Research Council, the daily recommended intake of chromium(III) is 50-200 μg. Several organic chromium(III) complexes have been reported to have significantly higher absorption and tissue incorporation activity than inorganic salts such as chromium(III) chloride.

  8. Biological monitoring of occupational exposure to different chromium compounds at various valency states

    Energy Technology Data Exchange (ETDEWEB)

    Mutti, A.; Pedroni, C.; Arfini, G.; Franchini, I.; Minoia, C.; Micoli, G.; Baldi, C.


    Chromium concentrations in the air were measured in seven different workroom environments, where exposure to water soluble hexavalent or trivalent compounds was expected. Urinary excretion of chromium was measured before and after the same arbitrarily chosen working day. End-of-shift urinary chromium and its increase above pre-exposure levels were closely related to the concentration of water soluble chromium (VI) in the air. The values corresponding to 50 micrograms m-3 in the air, which is the current threshold limit value in most countries, were 29.8 and 12.2 micrograms g-1 of creatinine, respectively. Urinary chromium in workers exposed to water insoluble chromates or to water soluble chromic (III) sulphate was definitely higher than that observed in subjects not occupationally exposed to chromium compounds, but it cannot be recommended as short-term exposure test for evaluation of the job-related hazard.

  9. Bioconcentration of chromium in edible mushrooms: influence of environmental and genetic factors. (United States)

    García, M A; Alonso, J; Melgar, M J


    Chromium concentrations were determined in 167 samples of wild edible mushrooms, collected from three different sites (urban, traffic and pastureland areas) in Lugo (NW Spain). The hymenophore (H) and the rest of the fruiting body (RFB) were analysed separately. The analyses were performed using inductively coupled plasma optical emission spectrometry (ICP-OES). The highest mean chromium levels (mg/kg dry weight) of 3.5 and 8.0, 4.5 and 6.2, and 6.2 and 4.3 were found in Lycoperdon utriforme, Coprinus comatus and Agaricus campestris in H and RFB, respectively. The highest concentrations of chromium were observed in terrestrial saprophytic species in relation to mycorrhizal species. With respect to the underlying substrates, chromium concentration was lowest in the pastureland area (24.6 mg/kg dw). All mushroom species were bioexclusors of chromium (BCFmushrooms harvested from the areas investigated poses no toxicological risk to human health due to chromium.

  10. Innovative soil treatment process design for removal of trivalent chromium

    Energy Technology Data Exchange (ETDEWEB)

    Stallings, J.H. [Air Force, Wright-Patterson AFB, OH (United States). Aeronautical Systems Center; Durkin, M.E. [Hughes Missile Systems Co., Tucson, AZ (United States)


    A soil treatment process has been developed as part of a US Air Force environmental compliance project at Air Force Plant 44, Tucson, AZ for treating soil contaminated with heavy metals including trivalent chromium, cadmium, copper, and nickel. The process was designed to treat a total of 133,000 tons of soil in a 400 ton per day facility. Features of the soil treatment process include physical treatment and separation, and a chemical treatment process of the remaining fines using a hypochlorite leach allowing chromium to be solubilized at a high pH. After treating, fines are washed in three stage countercurrent thickeners and chromium hydroxide cake is recovered as a final produce from the leach solution. Treatability studies were conducted, laboratory and a pilot plant was built. Process design criteria and flow sheet, material balances, as well as preliminary equipment selection and sizing for the facility have been completed. Facility was designed for the removal of Cr at a concentration of an average of 1230 mg/kg from the soil and meeting a risk based clean-closure limit of 400 mg/kg of Cr. Capital costs for the 400 tpd plant were estimated at 9.6 million with an operating and maintenance cost of $54 per ton As process is most economic for large quantities of soil with relatively low concentrations of contaminants, it was not used in final closure when the estimated volume of contaminated soil removed dropped to 65,000 tons and concentration of chromium increased up to 4000 mg/kg. However, the process could have application in situations where economics and location warrant.

  11. Chromium speciation in solid matrices and regulation: a review

    Energy Technology Data Exchange (ETDEWEB)

    Unceta, N. [University of the Basque Country, Department of Analytical Chemistry, Faculty of Pharmacy, Vitoria-Gasteiz (Spain); Seby, F. [Ultra Traces Analyses Aquitaine (UT2A), Helioparc Pau-Pyrenees, Pau (France); Malherbe, J.; Donard, O.F.X. [Universite de Pau et des Pays de l' Adour, Helioparc Pau-Pyrenees, Laboratoire de Chimie Analytique Bio-Inorganique et Environnement, IPREM, UMR CNRS 5254, Pau (France)


    In recent years, the extensive use of chromium in industrial processes has led to the promotion of several directives and recommendations by the European Union, that try to limit and regulate the presence of Cr(VI) in the environment and to protect industrial workers using chromium and end-users of manufactured products. As a consequence, new standard methods and analytical procedures have been published at the EU level for Cr(VI) determination in soil, sludge, sediment, and similar waste materials, workplace atmospheres, cement, packaging materials, industrially produced samples, and corrosion-protection layers on some components of vehicles and electrical and electronic equipment. The objective of this article is to summarize the different directives and recommendations and to critically review the currently existing standard methods and the methods published in the literature for chromium speciation in the above mentioned solid matrices, putting the emphasis on the different extraction procedures which have been developed for each matrix. Particular attention has been paid to Cr(III) and Cr(VI) inter-conversions that can occur during extraction and efforts to minimize these unwanted reactions. Although the use of NaOH-Na{sub 2}CO{sub 3} solutions with hot plate extraction seems to be the more widespread procedure, species transformation can still occur and several studies suggest that speciated isotope-dilution mass spectrometry (SIDMS) could be a suitable tool for correction of these interconversions. Besides, recent studies have proved the role of Cr(III) in chromium toxicology. As a consequence, the authors suggest an update of standard methods in the near future. (orig.)

  12. Technology Demonstration of the Zero Emissions Chromium Electroplating System (United States)


    blanket technology for electroplating tanks. When no liquid blanket is used, evaporation of water, especially during warm weather conditions, requires...0.007 0.004 0.002 Tank 12A had noticeable blobs floating on the surface and also at the interfacial layer of PRD fluid and the chromium acid solution...Tank 12B did not have any such blobs . All the parts removed after plating looked fairly good. There were no visible streaks, water breaks, etc. The

  13. Recovery of Chromium from Waste Taning Liquors by Magnesium Oxide

    Directory of Open Access Journals (Sweden)

    Mahmood M. Barbooti


    Full Text Available This is a case study of AL-Za’afaraniya tanning factory, 15 km to the south of Baghdad, to spot light on simple chemical treatment of the discharged water to solve the environmental problems associated with its chromium content management. The treatment was extended to the recovery and reuse of chromium. Chromium was precipitated by the addition of magnesium oxide which also aid as a neutralizer for the acidic effluent. The laboratory treatment was carried out to find the optimum conditions. The wastewater samples were taken from the outline area of the tannery. Box-Wilson method was adopted to find useful relationships between the operating variables (temperature, mixing period and magnesium oxide dose and the pH and chromium content of effluent. The experimental data were successfully fitted to second order polynomial mathematical models for the treatment. The most favorable operating conditions for the treatment were: temperature, 30 ºC; mixing period, 50 min and magnesium oxide concentration, 3000 mg/L. On using the optimum conditions a mathematical model simulating the operation for the treatment was obtained as follows:Cr = 6.0848 – 0.001839 X11 – 0.105334 X12 – 0.041038 X13pH = 10.29086 – 0.001223 X11 – 0.140043 X12 – 0.00953 X13Experimentally Cr concentration was decreased to about (0.5 mg/L in wastewater after raising the pH value to (7.35 by adding magnesium oxide.


    Directory of Open Access Journals (Sweden)

    V. M. Ilyushenko


    Full Text Available The article presents the results of the tests on the wear resistance of chromium cast irons of different compositions obtained in sand forms. It has been shown that increase of the wear resistance and mechanical properties of the cast iron is possible to obtain using the casting in metal molds. A further increase in wear resistance of parts produced in metal molds is possible by changing the technological parameters of casting and alloying by titanium.

  15. Evidence of weak ferromagnetism in chromium(III) oxide particles

    Energy Technology Data Exchange (ETDEWEB)

    Vazquez-Vazquez, Carlos E-mail:; Banobre-Lopez, Manuel; Lopez-Quintela, M.A.; Hueso, L.E.; Rivas, J


    The low temperature (4chromium(III) oxide particles have been studied. A clear evidence of the presence of weak ferromagnetism is observed below 250 K. The magnetisation curves as a function of the applied field show coercive fields due to the canted antiferromagnetism of the particles. Around 55 K a maximum is observed in the zero-field-cooled curves; this maximum can be assumed as a blocking temperature, similarly to ultrafine ferromagnetic particles.

  16. Magnetite nanoparticle (NP) uptake by wheat plants and its effect on cadmium and chromium toxicological behavior. (United States)

    López-Luna, J; Silva-Silva, M J; Martinez-Vargas, S; Mijangos-Ricardez, O F; González-Chávez, M C; Solís-Domínguez, F A; Cuevas-Díaz, M C


    The aim of this work was to assess the uptake of citrate-coated magnetite nanoparticles (NPs) by wheat plants and its effect on the bioaccumulation and toxicity of individual and joint Cd(2+) and Cr(6+) levels. Seven-day assays were conducted using quartz sand as the plant growth substrate. The endpoints measured were seed germination, root and shoot lengths, and heavy metal accumulation. Magnetite exhibited very low toxicity, regardless of the wheat seedling NP uptake and distribution into roots and shoots. The seed germination and shoot length were not sensitive enough, while the root length was a more sensitive toxicity endpoint. The root length of wheat seedlings exposed to individual metals decreased by 50% at 2.67mgCd(2)(+)kg(-1) and 5.53mgCr(6+)kg(-1). However, when magnetite NPs (1000mgkg(-1)) were added, the root length of the plants increased by 25 and 50%. Cd(2+) and Cr(6+) showed similar and noninteractive joint action, but strongly impaired the wheat seedlings. In contrast, an interactive infra-additive or antagonistic effect was observed upon adding magnetite NPs. Thus, cadmium and chromium accumulation in vegetable tissues was considerately diminished and the toxicity alleviated.

  17. Chromium related degradation of solid oxide fuel cells; Chrom-bezogene Degradation von Festoxid-Brennstoffzellen

    Energy Technology Data Exchange (ETDEWEB)

    Neumann, Anita


    Solid Oxide Fuel Cells (SOFCs) offer a high potential for application as an auxiliary power unit (APU) for heavy goods vehicles as well as combined heat and power (CHP) systems. SOFCs are especially attractive due to their high efficiencies and the use of different fuel types. However, optimization in terms of long term stability and costs are still necessary. This work characterized the degradation of SOFCs with lanthanum strontium manganite (LSM) cathodes under chromium influence. Galvanostatic cell tests were carried out at 800 C with operation times from 250 - 3000 h and variation of the chromium source and current density. The current densities of j = 0 (A)/(cm{sup 2}), j = 0,3 (A)/(cm{sup 2}) and j = 0,5 (A)/(cm{sup 2}) were applied. The high temperature ferritic alloy Crofer22APU was used as a chromium source. Variation of the chromium source was realized by coating the Crofer22APU insert with the chromium retention layer Mn{sub 3}O{sub 4} and the cathode contact layer LCC10. Cell degradation was analyzed with regard to cell voltage, current density and area specific resistance (ASR). Microstructural alterations of the cathode as well as chromium content and distribution across the cell were investigated after completion of the cell tests. For cells with a chromium source present and operation with a nonzero current density, the course of cell degradation was divided into three phases: a run-in, weak linear degradation and strong linear degradation. A decrease of the chromium release rate by means of different coatings stretched the course of degradation along the timescale. Strong degradation, which is characterized by a significant increase in ASR as well as a decrease of current density at the operating point, was only observed when a chromium source in the setup was comb ined with operation of the cell with a non-zero current density. Operation of the cell with a chromium source but no current density caused a degradation of current density at the

  18. Adsorptive stripping voltammetric determination of chromium in gallium. (United States)

    Palrecha, M M; Mathur, P K


    The electroanalytical chemistry of trace metals has progressed strongly with the development of cathodic stripping voltammetry (CSV) preceded by adsorption collection of organic metal complexes. A sensitive method for the determination of trace amount of chromium in gallium is described. Gallium is dissolved in sodium hydroxide containing hydrogen peroxide. The method is based on the catalytic activity of nitrate ions on the reduction of Cr(III)TTHA (triethylene tetramine-N,N,N',N'',N''',N'''-hexaacetic acid) complex. The sensitivity of this method is further improved by adsorption preconcentration of Cr(III)TTHA complex at a hanging mercury drop electrode (HMDE). The Cr(III) formed at the electrode surface by the reduction of Cr(VI), which is present in the bulk solution, is immediately complexed by TTHA. The adsorbed complex is then reduced at a peak potential of - 1.26 V, and the peak height of Cr(III) reduction is measured. The determination limit was restricted by the amount of chromium present in the reagent blank solution. The method is suitable for the determination of chromium at level as low as 0.2 mug g(-1) (with about 50 mg of sample) and a relative standard deviation of 15%.

  19. The chromium site in doped glassy lithium tetraborate

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, T.D. [Department of Engineering Physics, Air Force Institute of Technology, 2950 Hobson Way, Wright Patterson Air Force Base, OH 45433 (United States); Echeverria, E.; Beniwal, Sumit [Department of Physics and Astronomy, 855 North 16th Street, Theodore Jorgensen Hall, University of Nebraska-Lincoln, Lincoln, NE 68588-0299 (United States); Adamiv, V.T.; Burak, Ya. V.; Enders, Axel [Institute of Physical Optics, 23 Dragomanov Street, Lviv 79005 (Ukraine); Petrosky, J.C.; McClory, J.W. [Department of Engineering Physics, Air Force Institute of Technology, 2950 Hobson Way, Wright Patterson Air Force Base, OH 45433 (United States); Dowben, P.A., E-mail: [Department of Physics and Astronomy, 855 North 16th Street, Theodore Jorgensen Hall, University of Nebraska-Lincoln, Lincoln, NE 68588-0299 (United States)


    Using extended X-ray absorption fine structure (EXAFS) spectroscopy, we find that Cr substitutes primarily in the Li{sup +} site as a dopant in lithium tetraborate Li{sub 2}B{sub 4}O{sub 7} glasses, in this case 98.4Li{sub 2}B{sub 4}O{sub 7}–1.6Cr{sub 2}O{sub 3} or nominally Li{sub 1.98}Cr{sub 0.025}B{sub 4}O{sub 7}. This strong preference for a single site is nonetheless accompanied by site distortions and some site disorder, helping explain the optical properties of chromium doped Li{sub 2}B{sub 4}O{sub 7} glasses. The resulting O coordination shell has a contraction of the Cr–O bond lengths as compared to the Li–O bond lengths. There is also an increase in the O coordination number. - Graphical abstract: Lithium tetraborate: labeled are the B1 and B2 sites, where the latter correspond to BO{sub 3} and BO{sub 4} structures respectively. - Highlights: • Adoption of the Li + site for chromium dopants in lithium tetraborate identified. • Increased oxygen coordination for glass over the crystalline lithium tetraborate. • Distortions about the doping chromium characterized. • Local bond order is preserved in spite of the glassy nature.

  20. Chromium and manganese interactions in streptozocin-diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Davis, M.L.; Jarrett, C.R.; Adeleye, B.O.; Stoecker, B.J. (Oklahoma State Univ., Stillwater (United States))


    Weanling male rats were fed casein-based diets low in chromium and manganese ({minus}Cr-MN) or supplemented with 1 ppm chromium as chromium chloride (+Cr) and/or 55 ppm manganese as manganous carbonate in a factorial design. After 7 weeks on the experimental diets, half of the rats in each group were injected on 2 consecutive days with 55 mg/kg streptozocin (STZ) in citrate buffer pH 4. Four weeks after injection, serum glucose in the diabetic group supplement with both Cr and Mn was not different from non-diabetic animals; however, diabetic animals in {minus}Cr groups or in the +Cr-Mn group had significantly elevated serum glucose. Serum insulin was reduced by STZ. A significant interaction between Mn and diabetes affected serum cortisol concentrations. More new tissue was formed on a polyvinyl sponge inserted under the skin in +Mn animals. In this study, the STZ animals were more sensitive than the control animals to dietary Cr and Mn concentrations.

  1. Magnesium, zinc, and chromium nutriture and physical activity. (United States)

    Lukaski, H C


    Magnesium, zinc, and chromium are mineral elements required in modest amounts to maintain health and optimal physiologic function. For physically active persons, adequate amounts of these micronutrients are needed in the diet to ensure the capacity for increased energy expenditure and work performance. Most physically active individuals consume diets that provide amounts of magnesium and zinc sufficient to meet population standards. Women tend to consume less of these minerals than is recommended, in part because they eat less food than men. Inadequate intakes of magnesium and zinc have been reported for participants in activities requiring restriction of body weight. Dietary chromium is difficult to estimate because of a lack of appropriate reference databases. Acute, intense activity results in short-term increases in both urine and sweat losses of minerals that apparently diminish during recovery in the days after exercise. Supplemental magnesium and zinc apparently improve strength and muscle metabolism. However, evidence is lacking as to whether these observations relate to impaired nutritional status or a pharmacologic effect. Chromium supplementation of young men and women does not promote muscle accretion, fat loss, or gains in strength. Physically active individuals with concerns about meeting guidelines for nutrient intake should be counseled to select and consume foods with high nutrient densities rather than to rely on nutritional supplements. The indiscriminate use of mineral supplements can adversely affect physiologic function and impair health.

  2. Fabrication of chitosan-magnetite nanocomposite strip for chromium removal (United States)

    Sureshkumar, Vaishnavi; Kiruba Daniel, S. C. G.; Ruckmani, K.; Sivakumar, M.


    Environmental pollution caused by heavy metals is a serious threat. In the present work, removal of chromium was carried out using chitosan-magnetite nanocomposite strip. Magnetite nanoparticles (Fe3O4) were synthesized using chemical co-precipitation method at 80 °C. The nanoparticles were characterized using UV-visible spectroscopy, fourier transform infrared spectroscopy, X-ray diffraction spectrometer, atomic force microscope, dynamic light scattering and vibrating sample magnetometer, which confirm the size, shape, crystalline nature and magnetic behaviour of nanoparticles. Atomic force microscope revealed that the particle size was 15-30 nm and spherical in shape. The magnetite nanoparticles were mixed with chitosan solution to form hybrid nanocomposite. Chitosan strip was casted with and without nanoparticle. The affinity of hybrid nanocomposite for chromium was studied using K2Cr2O7 (potassium dichromate) solution as the heavy metal solution containing Cr(VI) ions. Adsorption tests were carried out using chitosan strip and hybrid nanocomposite strip at different time intervals. Amount of chromium adsorbed by chitosan strip and chitosan-magnetite nanocomposite strip from aqueous solution was evaluated using UV-visible spectroscopy. The results confirm that the heavy metal removal efficiency of chitosan-magnetite nanocomposite strip is 92.33 %, which is higher when compared to chitosan strip, which is 29.39 %.

  3. Foam separation of chromium (Ⅵ) from aqueous solution

    Institute of Scientific and Technical Information of China (English)

    JIAO Cai-shan; DING Yan


    Removal of chromium (Ⅵ) dissolved in water by intermittent foam separation was implemented with cetyl trimethy-ammonium bromide as surfactant. The influence of various factors on removal efficiency was systematically studied. The removal efficiency has a maximum value near pH 4.0; thus, most experiments were carried out at pH 4.0. The orthogonal experiment was conducted to confirm the optimal operating parameters. The orthogonal experimental results show that when the liquid feed concentration is 10 mg/L, the pH value of feed solution is 4.00, air flow rates 0.9 L/min, surfactant dosage is 300 mg/L, the maximum removal efficiency of chromium (Ⅵ) reaches 97.80%, and condense multiple reaches 1711. The kinetic test indicates that the foam separation of chromium is a first-order process. The equivalent rate constant calculated from the slope is 0.406 4, and the equivalent rate equation is obtained.

  4. Fabrication of Carbon Nanotube - Chromium Carbide Composite Through Laser Sintering (United States)

    Liu, Ze; Gao, Yibo; Liang, Fei; Wu, Benxin; Gou, Jihua; Detrois, Martin; Tin, Sammy; Yin, Ming; Nash, Philip; Tang, Xiaoduan; Wang, Xinwei


    Ceramics often have high hardness and strength, and good wear and corrosion resistance, and hence have many important applications, which, however, are often limited by their poor fracture toughness. Carbon nanotubes (CNTs) may enhance ceramic fracture toughness, but hot pressing (which is one typical approach of fabricating CNT-ceramic composites) is difficult to apply for applications that require localized heat input, such as fabricating composites as surface coatings. Laser beam may realize localized material sintering with little thermal effect on the surrounding regions. However, for the typical ceramics for hard coating applications (as listed in Ref.[1]), previous work on laser sintering of CNT-ceramic composites with mechanical property characterizations has been very limited. In this paper, research work has been reported on the fabrication and characterization of CNT-ceramic composites through laser sintering of mixtures of CNTs and chromium carbide powders. Under the studied conditions, it has been found that laser-sintered composites have a much higher hardness than that for plasma-sprayed composites reported in the literature. It has also been found that the composites obtained by laser sintering of CNTs and chromium carbide powder mixtures have a fracture toughness that is ~23 % higher than the material obtained by laser sintering of chromium carbide powders without CNTs.

  5. Response of soil catalase activity to chromium contamination

    Institute of Scientific and Technical Information of China (English)

    Zofia St(e)pniewska; Agnieszka Woli(n)ska; Joanna Ziomek


    The impact of chromium (III) and (VI) forms on soil catalase activity is presented.The Orthic Podzol, Haplic Phaeozem and Mollic Gleysol from different depths were used in the experiment.The soil samples were amended with solution of Cr(III) using CrCl3, and with Cr(VI) using K2Cr2O7 in the concentration range from 0 to 20 mg/kg, whereas the samples without the addition of chromium served as control.Catalase activity was assayed by one of the commonly used spectrophotometric methods.As it is demonstrated in the experiment, both Cr(III) and Cr(VI) forms have ability to reduce soil catalase activity.A chromium dose of 20 mg/kg caused the inhibition of catalase activity and the corresponding contamination levels ranged from 75% to 92% for Cr(III) and 68% to 76% for Cr(VI), with relation to the control.Catalase activity reached maximum in the soil material from surface layers (0-25 cm), typically characterized by the highest content of organic matter creating favorable conditions for microorganisms.

  6. Achieving Zero Stress in Iridium, Chromium, and Nickle Thin Films (United States)

    Broadway, David M.; Weimer, Jeffrey; Gurgew, Danielle; Lis, Tomasz; Ramsey, Brian D.; O'Dell, Stephen L.; Ames, A.; Bruni, R.


    We examine a method for achieving zero intrinsic stress in thin films of iridium, chromium, and nickel deposited by magnetron sputter deposition. The examination of the stress in these materials is motivated by efforts to advance the optical performance of light-weight x-ray space telescopes into the regime of sub-arc second resolution that rely on control of the film stress to values within 10-100 MPa. A characteristic feature of the intrinsic stress behavior in chromium and nickel is their sensitivity to the magnitude and sign of the intrinsic stress with argon gas pressure, including the existence of a critical pressure that results in zero film stress. This critical pressure scales linearly with the film's density. While the effect of stress reversal with argon pressure has been previously reported by Hoffman and others for nickel and chromium, we have discovered a similar behavior for iridium. Additionally, we have identified zero stress in iridium shortly after island coalescence. This feature of film growth is used for achieving a total internal stress of -2.89 MPa for a 15.8 nm thick iridium film. The surface roughness of this low-stress film was examined using scanning probe microscopy (SPM) and x-ray reflectivity (XRR) at CuKa and these results presented and discussed.

  7. 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;


    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...

  8. Simultaneously Recovering High-Purity Chromium and Removing Organic Pollutants from Tannery Effluent


    Jie Zong; Yan-Chun Li; Kang Hu


    Chromium pollution is a serious issue because of carcinogenic toxicities of the pollutants and low recovery rate of chromium because of the presence of organic, such as protein and fat. In this work, high recovery rate and high purity of the chromium ion were successfully prepared by the way of acid enzyme, flocculant, and Fenton oxidation. The experiments were characterized by TG, TOC, UV-VIS, and SEM. In the work, the tannery waste chrome liquor was used as experimental material. The result...

  9. Adsorption of Chromium(VI) from Aqueous Solutions by Coffee Polyphenol-Formaldehyde/Acetaldehyde Resins



    Removal of chromium(VI) from wastewater is essential as it is toxic. Thus, removal of chromium(VI) was performed using coffee polyphenol-formaldehyde/acetaldehyde resins as adsorbents. Adsorbent resins were prepared by condensation of decaffeinated coffee powder with formaldehyde/acetaldehyde and used for the removal of Cr(VI) ions from aqueous solutions. A simple and sensitive solid phase extraction procedure was applied for the determination of chromium at trace levels by spectroscopic meth...

  10. 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)



    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.

  11. 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.


    Directory of Open Access Journals (Sweden)

    R. L. T. de Andrade


    Full Text Available 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. Immediately after the slaughter, the carcasses were sent to sanitary maturation. After 24 hours, samples between 12th and 13th rib in the muscle Longissimus Thoracis were taken. For evaluation, it was used completely randomized design (Die and analysis of variance (ANOVA at 5% of significance level. The results didn't evidenced any significant difference (p>0,05 between the (cromo content, regardless the supplementation. The same happened with the digestion methods used.

  13. Advantages and Disadvantages of Chromium Salt%铬盐功过论(续)

    Institute of Scientific and Technical Information of China (English)



    对铬及其对人类的利害关系进行了详细的论述,包括铬与人体健康,铬在畜禽业中的应用,富铬农副产品的应用,铬鞣剂的不可取代性等。%Chromium as well as its advantages and disadvantages were introduced in detail,including chromium and human health,application in Livestock and Poultry Industry,Rich chromium agricultural and sideline products,Irreplaceable performance of chromium tanning agent,etc.

  14. Advantages and Disadvantages of Chromium Salt%铬盐功过论

    Institute of Scientific and Technical Information of China (English)



    Chromium as well as its advantages and disadvantages were introduced in detail, including chromium and human health, application in Livestock and Poultry Industry, Rich chromium agricultural and sideline products, Irreplaceable performance of chromium tanning agent, etc.%对铬及其对人类的利害关系进行了详细的论述,包括铬与人体健康,铬在畜禽业中的应用,富铬农副产品的应用,铬鞣剂的不可取代性等。

  15. Determination of total chromium in tanned leather samples used in car industry. (United States)

    Zeiner, Michaela; Rezić, Iva; Ujević, Darko; Steffan, Ilse


    Despite the high competition of synthetic fibers leather is nowadays still widely used for many applications. In order to ensure a sufficient stability of the skin matrix against many factors, such as microbial degradation, heat and sweat, a tanning process is indispensable. Using chromium (III) for this purpose offers a multitude of advantages, thus this way of tanning is widely applied. During the use of chromium tanned leather as clothing material as well as for decoration/covering purposes, chromium is extracted from the leather and may then cause nocuous effects to human skin, e.g. allergic reactions. Thus the knowledge of the total chromium content of leather samples expected to come into prolonged touch with human skin is very important. In car industry leather is used as cover for seats, steering wheel and gearshift lever The chromium contents often chromium tanned leather samples used in car industry were determined. First all samples were dried at 65 degrees C overnight and then cut in small pieces using a ceramic knife, weighed and analyzed by inductively coupled plasma--optical emission spectrometry (ICP-OES) after acidic microwave assisted digestion. The total chromium amounts found were in the range from 19 mg/g up to 32 mg/g. The extraction yield of chromium from leather samples in sweat is approximately 2-7%. Thus especially during long journeys in summer chromium can be extracted in amounts which may cause nocuous effects for example on the palm of the hands or on the back.

  16. The regeneration and recycle of chromium etching solutions using concentrator cell membrane technology. (United States)

    Chaudhary, Abdul J; Ganguli, Bijita; Grimes, Susan M


    The regeneration of chromium (VI) and the recovery of etched copper from chromium etching solutions by electrodialysis is improved by the addition of a concentrator cell in the catholyte chamber. The concentrator media used are ion-exchange resins or activated carbon cloth. The maximum percentages for the regeneration of chromium and recovery of copper in these systems is however less than 80% and 90% respectively because of the competition between the processes of oxidation of Cr(III) and electrodeposition of copper. A novel combination of electrolysis with electrodialysis and concentrator cell technology is developed that achieves 92% chromium regeneration and 90% copper recovery.

  17. Chromium status and glucose tolerance in Saudi men with and without coronary artery disease. (United States)

    Alissa, Eman M; Bahjri, Suhad M; Ahmed, Waqar H; Al-Ama, Nabeel; Ferns, Gordon A A


    Chromium deficiency is associated with impaired glucose tolerance (IGT) and dyslipidemia. Hence, the objective of the current study was to investigate chromium status among Saudi men with and without established cardiovascular disease (CVD) and its relationship to glucose tolerance, lipid profile and other established CVD risk factors. We measured serum and urine chromium concentrations, fasted lipid profile, plasma glucose, and serum lipid peroxide in 130 Saudi men with an established history of myocardial infarction and 130 age-matched controls without established CVD. Patients with established CVD had higher serum triglycerides (p < 0.05) and plasma glucose (p < 0.0001) and lower serum and urinary chromium concentrations (p < 0.0001) than controls. Serum chromium was inversely correlated with plasma glucose among cases and controls (r = -0.189, p < 0.05 and r = -0.354, p < 0.00001, respectively). Plasma glucose (OR 1.127, CI 1.0-1.269, p < 0.05), serum chromium (OR 0.99, CI 0.985-0.995, p < 0.0001), and urinary chromium (OR 0.988, CI 0.981-0.995, p < 0.001) were independently associated with the presence of established coronary disease applying this model. While chromium metabolism appears to be altered in individuals with CVD, it is unclear whether chromium supplementation would be effective in CVD prevention among patients with IGT. This would need to be tested in long-term outcome trials.

  18. The risk implications of the distribution of chromium forms in environmental media

    Energy Technology Data Exchange (ETDEWEB)

    Mahoney, L.A.; Petroff, D.M.; Batey, J.C. [Eckenfelder Inc., Nashville, TN (United States)


    Chromium exhibits multiple oxidation (valence) states, ranging from ({minus}2) to (+6). Under natural conditions, however, chromium typically exists in the Cr(III) (trivalent) and/or Cr(VI) (hexavalent) form, with the hexavalent form exhibiting higher solubility and much greater toxicity than the trivalent form. Due to the large differences in toxicity, the distribution of chromium oxidation states (Cr(III) and Cr(VI)) in site media is potentially of great importance to the calculation of site risk levels, and thus ultimately to cleanup activities. Despite its importance, chromium oxidation states are often not available for media samples collected at waste sites. Typical assumptions regarding the chromium distribution in site media are presented. Actual chromium distribution data from media from baseline investigations of several waste sites are also presented for groundwater, surface water, and soil and compared in terms of background chromium levels and the nature of site wastes. The differences in toxicity of Cr(III) and Cr(VI) are briefly discussed. Risk estimates and risk-based cleanup levels generated using different assumptions for the distribution of chromium in site media for a selected example site are then given. These risk-based cleanup levels are compared to various state regulatory limits, MCLs, and Practical Quantitation Limits (PQLs) for chromium.

  19. The prevalence of chromium allergy in Denmark is currently increasing as a result of leather exposure

    DEFF Research Database (Denmark)

    Thyssen, J P; Jensen, P; Carlsen, B C;


    previously been demonstrated among Danish construction workers. OBJECTIVES: To investigate the development of chromium allergy among patients with dermatitis tested between 1985 and 2007 in Denmark. Furthermore, to determine causative exposures in patients with chromium allergy. PATIENTS AND METHODS......: A retrospective analysis of patch test data was performed (n = 16,228) and charts from patients with chromium allergy were reviewed. Comparisons were made using a chi(2) test. Logistic regression analyses were used to test for associations. RESULTS: The prevalence of chromium allergy decreased significantly from...

  20. Clinical utility of recombinant adenoviral human p53 gene therapy: current perspectives

    Directory of Open Access Journals (Sweden)

    Chen GX


    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