Cadmium resistance in tobacco plants expressing the MuSI gene.

Science.gov (United States)

Kim, Young-Nam; Kim, Ji-Seoung; Seo, Sang-Gyu; Lee, Youngwoo; Baek, Seung-Woo; Kim, Il-Sup; Yoon, Ho-Sung; Kim, Kwon-Rae; Kim, Sun-Hyung; Kim, Kye-Hoon

2011-10-01

MuSI, a gene that corresponds to a domain that contains the rubber elongation factor (REF), is highly homologous to many stress-related proteins in plants. Since MuSI is up-regulated in the roots of plants treated with cadmium or copper, the involvement of MuSI in cadmium tolerance was investigated in this study. Escherichia coli cells overexpressing MuSI were more resistant to Cd than wild-type cells transfected with vector alone. MuSI transgenic plants were also more resistant to Cd. MuSI transgenic tobacco plants absorbed less Cd than wild-type plants. Cd translocation from roots to shoots was reduced in the transgenic plants, thereby avoiding Cd toxicity. The number of short trichomes in the leaves of wild-type tobacco plants was increased by Cd treatment, while this was unchanged in MuSI transgenic tobacco. These results suggest that MuSI transgenic tobacco plants have enhanced tolerance to Cd via reduced Cd uptake and/or increased Cd immobilization in the roots, resulting in less Cd translocation to the shoots.

Overexpression of metallothionein in CHO cells and its effect on cell killing by ionizing radiation and alkylating agents

International Nuclear Information System (INIS)

Lohrer, H.; Robson, T.

1989-01-01

Metallothionein protein protects cells from the toxic effects of heavy metal ions. To establish its protective function against ionizing radiation and alkylating agents, a model system was created by transfecting two CHO cell lines (wild-type, K1-2 and X-ray sensitive, xrs-2 subclone Bc11) with the human metallothionein II-A (hMTII-A) gene integrated in a bovine papilloma derived autonomously replicating vector. The isolated transfectants are cadmium-resistant (Cd 1 ), due to the overexpression of the hMTII-A gene. Their steady-state level of hMTII-A mRNA can be increased up to 40-fold after Cd treatment and 20-fold after induction with ionizing radiation. The transfected cell lines proved to be as sensitive as the recipient cell lines to ionizing radiation and bleomycin but the transfectants were significantly more resistant to N-methyl-nitro-nitrosoguanidine (MNNG) and mitomycin C (MMC). These results lead to the conclusion that the MT protein does provide a defence mechanism to protect cells from monofunctional alkylating and cross-linking agents but not from free radicals. (author)

Overexpression of metallothionein in CHO cells and its effect on cell killing by ionizing radiation and alkylating agents

Energy Technology Data Exchange (ETDEWEB)

Lohrer, H.; Robson, T. (Newcastle upon Tyne Univ. (UK). Cancer Research Unit)

1989-12-01

Metallothionein protein protects cells from the toxic effects of heavy metal ions. To establish its protective function against ionizing radiation and alkylating agents, a model system was created by transfecting two CHO cell lines (wild-type, K1-2 and X-ray sensitive, xrs-2 subclone Bc11) with the human metallothionein II-A (hMTII-A) gene integrated in a bovine papilloma derived autonomously replicating vector. The isolated transfectants are cadmium-resistant (Cd{sup 1}), due to the overexpression of the hMTII-A gene. Their steady-state level of hMTII-A mRNA can be increased up to 40-fold after Cd treatment and 20-fold after induction with ionizing radiation. The transfected cell lines proved to be as sensitive as the recipient cell lines to ionizing radiation and bleomycin but the transfectants were significantly more resistant to N-methyl-nitro-nitrosoguanidine (MNNG) and mitomycin C (MMC). These results lead to the conclusion that the MT protein does provide a defence mechanism to protect cells from monofunctional alkylating and cross-linking agents but not from free radicals. (author).

A new homolog of FocA transporters identified in cadmium-resistant Euglena gracilis

International Nuclear Information System (INIS)

Delomenie, Claudine; Foti, Emilie; Floch, Enora; Diderot, Vimala; Porquet, Dominique; Dupuy, Corinne; Bonaly, Jacqueline

2007-01-01

To better understand the cellular mechanism of stress resistance to various pollutants (cadmium, pentachlorophenol), we undertook a survey of the Euglena gracilis transcriptome by mRNA differential display and cDNA cloning. We performed a real-time RT-PCR analysis upon four selected genes. One of them significantly changed its expression level in response to stress treatments: B25 gene was overexpressed in Cd-resistant cells whereas it was down-regulated in PCP-adapted cells. By Race assays we obtained for B25 a 1093 bp cDNA. The deduced protein was identified as a bacterial formate/nitrite transporter (FocA) homolog and the gene was named EgFth. From all the data, we concluded that EgFth overexpression was related to chronic exposure to cadmium

GCKR variants increase triglycerides while protecting from insulin resistance in Chinese children.

Science.gov (United States)

Shen, Yue; Wu, Lijun; Xi, Bo; Liu, Xin; Zhao, Xiaoyuan; Cheng, Hong; Hou, Dongqing; Wang, Xingyu; Mi, Jie

2013-01-01

Variants in gene encoding glucokinase regulator protein (GCKR) were found to have converse effects on triglycerides and glucose metabolic traits. We aimed to investigate the influence of GCKR variants for triglycerides and glucose metabolic traits in Chinese children and adults. We genotyped two GCKR variants rs1260326 and rs1260333 in children and adults, and analyzed the association between two variants and triglycerides, glucose, insulin and HOMA-IR using linear regression model, and estimated the effect on insulin resistance using logistic regression model. Rs1260326 and rs1260333 associated with increased triglycerides in children and adults (ptriglycerides in Chinese children and adults. Triglycerides-increasing alleles of GCKR variants reduce insulin and HOMA-IR index, and protect from insulin resistance in children. Our results suggested GCKR has an effect on development of insulin resistance in Chinese children.

Evolution of simeprevir-resistant variants over time by ultra-deep sequencing in HCV genotype 1b.

Science.gov (United States)

Akuta, Norio; Suzuki, Fumitaka; Sezaki, Hitomi; Suzuki, Yoshiyuki; Hosaka, Tetsuya; Kobayashi, Masahiro; Kobayashi, Mariko; Saitoh, Satoshi; Ikeda, Kenji; Kumada, Hiromitsu

2014-08-01

Using ultra-deep sequencing technology, the present study was designed to investigate the evolution of simeprevir-resistant variants (amino acid substitutions of aa80, aa155, aa156, and aa168 positions in HCV NS3 region) over time. In Toranomon Hospital, 18 Japanese patients infected with HCV genotype 1b, received triple therapy of simeprevir/PEG-IFN/ribavirin (DRAGON or CONCERT study). Sustained virological response rate was 67%, and that was significantly higher in patients with IL28B rs8099917 TT than in those with non-TT. Six patients, who did not achieve sustained virological response, were tested for resistant variants by ultra-deep sequencing, at the baseline, at the time of re-elevation of viral loads, and at 96 weeks after the completion of treatment. Twelve of 18 resistant variants, detected at re-elevation of viral load, were de novo resistant variants. Ten of 12 de novo resistant variants become undetectable over time, and that five of seven resistant variants, detected at baseline, persisted over time. In one patient, variants of Q80R at baseline (0.3%) increased at 96-week after the cessation of treatment (10.2%), and de novo resistant variants of D168E (0.3%) also increased at 96-week after the cessation of treatment (9.7%). In conclusion, the present study indicates that the emergence of simeprevir-resistant variants after the start of treatment could not be predicted at baseline, and the majority of de novo resistant variants become undetectable over time. Further large-scale prospective studies should be performed to investigate the clinical utility in detecting simeprevir-resistant variants. © 2014 Wiley Periodicals, Inc.

Selective extraction-photometric determination of cadmium by basic dyes

Energy Technology Data Exchange (ETDEWEB)

Kish, P P; Balog, J S [Uzhgorodskij Gosudarstvennyj Univ. (Ukrainian SSR)

1979-12-01

Two variants of selective extraction-photometric determination of cadmium with basic dyes have been developed. In the first one, cadmium is extracted as the iodide by a tributyl phosphate solution in benzene from aqueous solutions containing 0.1 M KI (pH 6-10). Then the cadmium is transformed into a coloured ion associate by treatment of the extracts with Malachite Green in the presence of iodide ions. In the second case, the extract is equilibrated with an equeous solutions of Rhodamine B in the presence of KBr. In this variant, the cadmium is transformed into an anionic iodide-bromide complex which reacts with Rhodamine B cations to form an ion associate. Procedures have been developed of selective extraction-photometric determination of cadmium in sulphur, indium-gallium and zinc concentrates, Zn-As-Cd-Se and Zn-As-Cd-Te films, Cd-S-In and Ga-Sb-Cd-Te alloys.

The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line

DEFF Research Database (Denmark)

Xu, Xun; Pan, Shengkai; Liu, Xin

2011-01-01

Chinese hamster ovary (CHO)-derived cell lines are the preferred host cells for the production of therapeutic proteins. Here we present a draft genomic sequence of the CHO-K1 ancestral cell line. The assembly comprises 2.45 Gb of genomic sequence, with 24,383 predicted genes. We associate most....... Homologs of most human glycosylation-associated genes are present in the CHO-K1 genome, although 141 of these homologs are not expressed under exponential growth conditions. Many important viral entry genes are also present in the genome but not expressed, which may explain the unusual viral resistance...... property of CHO cell lines. We discuss how the availability of this genome sequence may facilitate genome-scale science for the optimization of biopharmaceutical protein production....

[The role of Cd-binding proteins and phytochelatins in the formation of cadmium resistance in Nicotiana plumbaginifolia cell lines].

Science.gov (United States)

Fenik, S I; Solodushko, V G; Kaliniak, T B; Blium, Ia B

2007-01-01

Nicotiana plumbaginifolia callus lines with the equal resistance to cadmium have been produced under different selective conditions--either without inhibition of the phytochelatin synthesis (line Cd-R) or in the presence of the inhibitor butionine sulfoximine (line Cd-Ri). The level of phytochelatin synthesis in the line Cd-R five-fold exceeded the control value and in the line Cd-Ri it was twice as much as in the control. It was shown that in the control line mainly three cadmium-binding proteins are expressed of the molecular weihgts 41, 34 and 19 kD. The common feature of the both resistant lines is the expression of the cadmium-binding proteins of 40, 37 and 19 kD. The resistant lines differ with respect to the synthesis of relatively low-molecular cadmium-binding proteins. The proteins of the molecular weights 12.5, 11.5 and 9 kD are expressed in the line Cd-R, while the proteins of 13 and 10 kD are expressed in the line Cd-Ri. It was supposed that both the phytochelatins and the Cd-binding proteins contribute to the resisitance of N. plumbaginifolia callus lines to cadmium and the lack of the phytochelatins can be equilibrated by the changes in the low-molecular Cd-binding protein synthesis.

Elucidation of the CHO Super-Ome (CHO-SO) by Proteoinformatics

DEFF Research Database (Denmark)

Kumar, Amit; Baycin-Hizal, Deniz; Wolozny, Daniel

2015-01-01

-SO), or superome. As a part of this effort, we created a publically accessible web-based tool called GO-CHO to functionally categorize proteins found in CHO-SO and identify enriched molecular functions, biological processes, and cellular components. We also used a tool to evaluate the immunogenicity potential...

Functional heterogeneity and heritability in CHO cell populations.

Science.gov (United States)

Davies, Sarah L; Lovelady, Clare S; Grainger, Rhian K; Racher, Andrew J; Young, Robert J; James, David C

2013-01-01

isolate CHO cell variants with improved functional properties in vitro. Copyright © 2012 Wiley Periodicals, Inc.

Impact of Pathogen Population Heterogeneity and Stress-Resistant Variants on Food Safety.

Science.gov (United States)

Abee, T; Koomen, J; Metselaar, K I; Zwietering, M H; den Besten, H M W

2016-01-01

This review elucidates the state-of-the-art knowledge about pathogen population heterogeneity and describes the genotypic and phenotypic analyses of persister subpopulations and stress-resistant variants. The molecular mechanisms underlying the generation of persister phenotypes and genetic variants are identified. Zooming in on Listeria monocytogenes, a comparative whole-genome sequence analysis of wild types and variants that enabled the identification of mutations in variants obtained after a single exposure to lethal food-relevant stresses is described. Genotypic and phenotypic features are compared to those for persistent strains isolated from food processing environments. Inactivation kinetics, models used for fitting, and the concept of kinetic modeling-based schemes for detection of variants are presented. Furthermore, robustness and fitness parameters of L. monocytogenes wild type and variants are used to model their performance in food chains. Finally, the impact of stress-resistant variants and persistence in food processing environments on food safety is discussed.

Functional characterization of a cadmium resistance operon in Staphylococcus aureus ATCC12600: CadC does not function as a repressor.

Science.gov (United States)

Hoogewerf, Arlene J; Dyk, Lisa A Van; Buit, Tyler S; Roukema, David; Resseguie, Emily; Plaisier, Christina; Le, Nga; Heeringa, Lee; Griend, Douglas A Vander

2015-02-01

Sequencing of a cadmium resistance operon from a Staphylococcus aureus ATCC12600 plasmid revealed that it is identical to a cadCA operon found in MRSA strains. Compared to plasmid-cured and cadC-mutant strains, cadC-positive ATCC12600 cells had increased resistance to cadmium (1 mg ml(-1) cadmium sulfate) and zinc (4 mg ml(-1) zinc sulfate), but not to other metal ions. After growth in media containing 20 µg ml(-1) cadmium sulfate, cadC-mutant cells contained more intracellular cadmium than cadC-positive ATCC12600 cells, suggesting that cadC absence results in impaired cadmium efflux. Electrophoretic mobility shift assays were performed with CadC proteins encoded by the S. aureus ATCC12600 plasmid and by the cadC gene of pI258, which is known to act as a transcriptional repressor and shares only 47% protein sequence identity with ATCC12600 CadC. Mobility shifts occurred when pI258 CadC protein was incubated with the promoter DNA-regions from the pI258 and S. aureus ATCC12600 cadCA operons, but did not occur with S. aureus ATCC12600 CadC protein, indicating that the ATCC12600 CadC protein does not interact with promoter region DNA. This cadCA operon, found in MRSA strains and previously functionally uncharacterized, increases resistance to cadmium and zinc by an efflux mechanism, and CadC does not function as a transcriptional repressor. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cloning and occurrence of czrC, a gene conferring cadmium and zinc resistance in MRSA CC398 Isolates

DEFF Research Database (Denmark)

Cavaco, Lina; Hasman, Henrik; Stegger, Marc

2010-01-01

the genetic determinant causing zinc resistance in CC398 and examine its prevalence in isolates of animal and human origin. Based on the sequence of the staphylococcal cassette chromosome mec (SCCmec) element from methicillin-resistant S. aureus (MRSA) CC398 strain SO385, a putative metal resistance gene......-four percent (n = 23) of the animal isolates and 48% (n = 24) of the human MRSA isolates of CC398 were resistant to zinc chloride and positive for czrC. All 48 MSSA strains from both human and pig origins were found to be susceptible to zinc chloride and negative for czrC. Our findings showed that czr......C is encoding zinc and cadmium resistance in CC398 MRSA isolates, and that it is widespread both in humans and animals. Thus, resistance to heavy metals such as zinc and cadmium may play a role in the coselection of methicillin resistance in S. aureus....

The art of CHO cell engineering: A comprehensive retrospect and future perspectives.

Science.gov (United States)

Fischer, Simon; Handrick, René; Otte, Kerstin

2015-12-01

Chinese hamster ovary (CHO) cells represent the most frequently applied host cell system for industrial manufacturing of recombinant protein therapeutics. CHO cells are capable of producing high quality biologics exhibiting human-like post-translational modifications in gram quantities. However, production processes for biopharmaceuticals using mammalian cells still suffer from cellular limitations such as limited growth, low productivity and stress resistance as well as higher expenses compared to bacterial or yeast based expression systems. Besides bioprocess, media and vector optimizations, advances in host cell engineering technologies comprising introduction, knock-out or post-transcriptional silencing of engineering genes have paved the way for remarkable achievements in CHO cell line development. Furthermore, thorough analysis of cellular pathways and mechanisms important for bioprocessing steadily unravels novel target molecules which might be addressed by functional genomic tools in order to establish superior production cell factories. This review provides a comprehensive summary of the most fundamental achievements in CHO cell engineering over the past three decades. Finally, the authors discuss the potential of novel and innovative methodologies that might contribute to further enhancement of existing CHO based production platforms for biopharmaceutical manufacturing in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

Studies on a morphologically distinct colchicine-resistance variant of Entamoeba sp.

Science.gov (United States)

Injeyan, H; Huebner, E; Meerovitch, E

1979-05-01

Colchicine has a temperature-dependent cytotoxic effect on Entamoeba sp. (Laredo isolate) that is most apparent when the drug is applied during the initiation of cultures at a concentration of 7.5 mM or higher. Continued transfer of cultures in medium containing progressively increasing concentrations of colchicine has resulted in a variant that grows prolifically in the presence of colchicine (7.5 mM) with a generation time comparable to that of the parent stock, Comparison of a number of parameters of the 2 variants revealed that colchicine resistance was accompanied by a change in cell shape, a reduced membrane permeability, which could partially be overcome by the addition of dimethyl sulfoxide (DMSO), and a reduced tolerance to osmotic stress. However, the parent strain and resistant variant were equally susceptible to cycloheximide and puromycin suggesting that the acquired colchicine resistance may not be explained on the basis of an entirely unspecific generalized reduced ability for drug uptake. Colchicine resistance and altered structure were found to be stable over a long period of time. The possible interdependence of these 2 parameters and their relation to cell motility in Entamoeba sp. are discussed.

Antibacterial efficacy of Nisin, Pediocin 34 and Enterocin FH99 against Listeria monocytogenes and cross resistance of its bacteriocin resistant variants to common food preservatives.

Science.gov (United States)

Kaur, G; Singh, T P; Malik, R K

2013-01-01

Antilisterial efficiency of three bacteriocins, viz, Nisin, Pediocin 34 and Enterocin FH99 was tested individually and in combination against Listeria mononcytogenes ATCC 53135. A greater antibacterial effect was observed when the bacteriocins were combined in pairs, indicating that the use of more than one LAB bacteriocin in combination have a higher antibacterial action than when used individually. Variants of Listeria monocytogenes ATCC 53135 resistant to Nisin, Pediocin 34 and Enterocin FH99 were developed. Bacteriocin cross-resistance of wild type and their corresponding resistant variants were assessed and results showed that resistance to a bacteriocin may extend to other bacteriocins within the same class. Resistance to Pediocin 34 conferred cross resistance to Enterocin FH 99 but not to Nisin. Similarly resistance to Enterocin FH99 conferred cross resistance to Pediocin 34 but not to Nisin. Also, the sensitivity of Nisin, Pediocin 34 and Enterocin FH99 resistant variants of Listeria monocytogenes to low pH, salt, sodium nitrite, and potassium sorbate was assayed in broth and compared to the parental wild-type strain. The Nisin, Pediocin 34 and Enterocin FH99 resistant variants did not have intrinsic resistance to low pH, sodium chloride, potassium sorbate, or sodium nitrite. In no case were the bacteriocin resistant Listeria monocytogenes variants examined were more resistant to inhibitors than the parental strains.

Antibacterial efficacy of Nisin, Pediocin 34 and Enterocin FH99 against Listeria monocytogenes and cross resistance of its bacteriocin resistant variants to common food preservatives

Directory of Open Access Journals (Sweden)

G. Kaur

2013-01-01

Full Text Available Antilisterial efficiency of three bacteriocins, viz, Nisin, Pediocin 34 and Enterocin FH99 was tested individually and in combination against Listeria mononcytogenes ATCC 53135. A greater antibacterial effect was observed when the bacteriocins were combined in pairs, indicating that the use of more than one LAB bacteriocin in combination have a higher antibacterial action than when used individually. Variants of Listeria monocytogenes ATCC 53135 resistant to Nisin, Pediocin 34 and Enterocin FH99 were developed. Bacteriocin cross-resistance of wild type and their corresponding resistant variants were assessed and results showed that resistance to a bacteriocin may extend to other bacteriocins within the same class. Resistance to Pediocin 34 conferred cross resistance to Enterocin FH 99 but not to Nisin. Similarly resistance to Enterocin FH99 conferred cross resistance to Pediocin 34 but not to Nisin. Also, the sensitivity of Nisin, Pediocin 34 and Enterocin FH99 resistant variants of Listeria monocytogenes to low pH, salt, sodium nitrite, and potassium sorbate was assayed in broth and compared to the parental wild-type strain. The Nisin, Pediocin 34 and Enterocin FH99 resistant variants did not have intrinsic resistance to low pH, sodium chloride, potassium sorbate, or sodium nitrite. In no case were the bacteriocin resistant Listeria monocytogenes variants examined were more resistant to inhibitors than the parental strains.

Modeling and Validation of the Ecological Behavior of Wild-Type Listeria monocytogenes and Stress-Resistant Variants.

Science.gov (United States)

Metselaar, Karin I; Abee, Tjakko; Zwietering, Marcel H; den Besten, Heidy M W

2016-09-01

Listeria monocytogenes exhibits a heterogeneous response upon stress exposure which can be partially attributed to the presence of stable stress-resistant variants. This study aimed to evaluate the impact of the presence of stress-resistant variants of Listeria monocytogenes and their corresponding trade-offs on population composition under different environmental conditions. A set of stress robustness and growth parameters of the wild type (WT) and an rpsU deletion variant was obtained and used to model their growth behavior under combined mild stress conditions and to model their kinetics under single- and mixed-strain conditions in a simulated food chain. Growth predictions for the WT and the rpsU deletion variant matched the experimental data generally well, although some deviations from the predictions were observed. The data highlighted the influence of the environmental conditions on the ratio between the WT and variant. Prediction of performance in the simulated food chain proved to be challenging. The trend of faster growth and lower stress robustness for the WT than for the rpsU variant in the different steps of the chain was confirmed, but especially for the inactivation steps and the time needed to resume growth after an inactivation step, the experimental data deviated from the model predictions. This report provides insights into the conditions which can select for stress-resistant variants in industrial settings and discusses their potential persistence in food processing environments. Listeria monocytogenes exhibits a heterogeneous stress response which can partially be attributed to the presence of genetic variants. These stress-resistant variants survive better under severe conditions but have, on the other hand, a reduced growth rate. To date, the ecological behavior and potential impact of the presence of stress-resistant variants is not fully understood. In this study, we quantitatively assessed growth and inactivation behavior of wild-type L

Blast resistance of space-induced variants derived from rice cultivar Hanghui 7

International Nuclear Information System (INIS)

Zhang Jingxin; Yang Qiyun; Zhu Xiaoyuan; Wang Hui; Zeng Liexian; Liu Yongzhu; Guo Tao; Chen Zhiqiang

2010-01-01

To screen the resistance lines to rice blast, the blast resistance of SP 3 and SP 4 progenies derived from rice variety Hanghui 7 were evaluated after satellite flight, and the genomic DNA polymorphism of the resistant variants selected from SP 3 was compared with the wild type by microsatellite markers. The results indicated that the SP 3 Variant line H24, which was selected from the 250 space-induced lines ( SP 3 ) with excellent agronomic and economical characters, showed resistance segregation (119R : 108S) against blast isolate GD3286. It was demonstrated that the resistance of H24 might be controlled by two dominant and complementary resistance genes. The resistance of H24 was still segregated in SP 4 , but the resistance spectrum of H24 was 84. 4% in SP 5 , much higher than the wild type, 40. 6%, and H24 especially showed resistant against some blast isolates of broad pathogenic spectrum or specialized pathogenicity; further more, the DNA polymorphism wasn't detected between H24 and its wild type by 229 SSR (simple sequence repeat) markers covering the rice genome equally. (authors)

Coagulation factor VII variants resistant to inhibitory antibodies.

Science.gov (United States)

Branchini, Alessio; Baroni, Marcello; Pfeiffer, Caroline; Batorova, Angelika; Giansily-Blaizot, Muriel; Schved, Jean F; Mariani, Guglielmo; Bernardi, Francesco; Pinotti, Mirko

2014-11-01

Replacement therapy is currently used to prevent and treat bleeding episodes in coagulation factor deficiencies. However, structural differences between the endogenous and therapeutic proteins might increase the risk for immune complications. This study was aimed at identifying factor (F)VII variants resistant to inhibitory antibodies developed after treatment with recombinant activated factor VII (rFVIIa) in a FVII-deficient patient homozygous for the p.A354V-p.P464Hfs mutation, which predicts trace levels of an elongated FVII variant in plasma. We performed fluorescent bead-based binding, ELISA-based competition as well as fluorogenic functional (activated FX and thrombin generation) assays in plasma and with recombinant proteins. We found that antibodies displayed higher affinity for the active than for the zymogen FVII (half-maximal binding at 0.54 ± 0.04 and 0.78 ± 0.07 BU/ml, respectively), and inhibited the coagulation initiation phase with a second-order kinetics. Isotypic analysis showed a polyclonal response with a large predominance of IgG1. We hypothesised that structural differences in the carboxyl-terminus between the inherited FVII and the therapeutic molecules contributed to the immune response. Intriguingly, a naturally-occurring, poorly secreted and 5-residue truncated FVII (FVII-462X) escaped inhibition. Among a series of truncated rFVII molecules, we identified a well-secreted and catalytically competent variant (rFVII-464X) with reduced binding to antibodies (half-maximal binding at 0.198 ± 0.003 BU/ml) as compared to the rFVII-wt (0.032 ± 0.002 BU/ml), which led to a 40-time reduced inhibition in activated FX generation assays. Taken together our results provide a paradigmatic example of mutation-related inhibitory antibodies, strongly support the FVII carboxyl-terminus as their main target and identify inhibitor-resistant FVII variants.

CHO Quasispecies—Implications for Manufacturing Processes

Directory of Open Access Journals (Sweden)

Florian M. Wurm

2013-10-01

Full Text Available Chinese hamster ovary (CHO cells are a source of multi-ton quantities of protein pharmaceuticals. They are, however, immortalized cells, characterized by a high degree of genetic and phenotypic diversity. As is known for any biological system, this diversity is enhanced by selective forces when laboratories (no sharing of gene pools grow cells under (diverse conditions that are practical and useful. CHO cells have been used in culture for more than 50 years, and various lines of cells are available and have been used in manufacturing. This article tries to represent, in a cursory way, the history of CHO cells, particularly the origin and subsequent fate of key cell lines. It is proposed that the name CHO represents many different cell types, based on their inherent genetic diversity and their dynamic rate of genetic change. The continuing remodeling of genomic structure in clonal or non-clonal cell populations, particularly due to the non-standardized culture conditions in hundreds of different labs renders CHO cells a typical case for “quasispecies”. This term was coined for families of related (genomic sequences exposed to high mutation rate environments where a large fraction of offspring is expected to carry one or more mutations. The implications of the quasispecies concept for CHO cells used in protein manufacturing processes are significant. CHO genomics/transcriptomics may provide only limited insights when done on one or two “old” and poorly characterized CHO strains. In contrast, screening of clonal cell lines, derived from a well-defined starting material, possibly within a given academic or industrial environment, may reveal a more narrow diversity of phenotypes with respect to physiological/metabolic activities and, thus, allow more precise and reliable predictions of the potential of a clone for high-yielding manufacturing processes.

Clinical Relevance of Androgen Receptor Splice Variants in Castration-Resistant Prostate Cancer.

Science.gov (United States)

Maughan, Benjamin L; Antonarakis, Emmanuel S

2015-12-01

Metastatic castration-resistant prostate cancer (mCRPC) currently benefits from a wealth of treatment options, yet still remains lethal in the vast majority of patients. It is becoming increasingly understood that this disease entity continues to evolve over time, acquiring additional and diverse resistance mechanisms with each subsequent therapy used. This dynamic relationship between treatment pressure and disease resistance can be challenging for the managing clinician. The recent discovery of alternate splice variants of the androgen receptor (AR) is one potential mechanism of escape in mCRPC, and recognizing this resistance mechanism might be important for optimal treatment selection for our patients. AR-V7 appears to be the most relevant AR splice variant, and early clinical data suggest that it is a negative prognostic marker in mCRPC. Emerging evidence also suggests that detection of AR-V7 may be associated with resistance to novel hormonal therapy (abiraterone and enzalutamide) but may be compatible with sensitivity to taxane chemotherapy (docetaxel and cabazitaxel). Adding to this complexity is the observation that AR-V7 is a dynamic marker whose status may change across time and depending on selective pressures induced by different therapies. Finally, it is possible that AR-V7 may represent a therapeutic target in mCRPC if drugs can be designed that degrade or inhibit AR splice variants or block their transcriptional activity. Several such agents (including galeterone, EPI-506, and bromodomain/BET inhibitors) are now in clinical development.

Cadmium tolerance and antibiotic resistance in Escherichia coli isolated from waste stabilization ponds.

Science.gov (United States)

Patra, Sova; Das, T K; Avila, C; Cabello, V; Castillo, F; Sarkar, D; Lahiri, Susmita; Jana, B B

2012-04-01

The incidence pattern of cadmium tolerance and antibiotics resistance by Escherichia coli was examined periodically from the samples of water, sludge and intestine of fish raised in waste stabilization ponds in a sewage treatment plant. Samples of water and sludge were collected from all the selected ponds and were monitored for total counts of fecal coliform (FC), total coliform (TC) and the population of Escherichia coli, which was also obtained from the intestine of fishes. Total counts of both FC and TC as well as counts of E. coli were markedly reduced from the facultative pond to the last maturation pond. Tolerance limit to cadmium by E. coli tended to decline as the distance of the sewage effluent from the source increased; the effective lethal concentration of cadmium ranged from 0.1 mM in split chamber to 0.05 mM in first maturation pond. E. coli isolated from water, sludge and fish gut were sensitive to seven out of ten antibiotics tested. It appears that holistic functions mediated through the mutualistic growth of micro algae and heterotrophic bacteria in the waste stabilization ponds were responsible for the promotion of water quality and significant reduction of coliform along the sewage effluent gradient.

White matter NAA/Cho and Cho/Cr ratios at MR spectroscopy are predictive of motor outcome in preterm infants.

Science.gov (United States)

Kendall, Giles S; Melbourne, Andrew; Johnson, Samantha; Price, David; Bainbridge, Alan; Gunny, Roxanna; Huertas-Ceballos, Angela; Cady, Ernest B; Ourselin, Sebastian; Marlow, Neil; Robertson, Nicola J

2014-04-01

To determine (a) whether diffuse white matter injury of prematurity is associated with an increased choline (Cho)-to-creatine (Cr) ratio and a reduced N-acetylaspartate (NAA)-to-Cho ratio and whether these measures can be used as biomarkers of outcome and (b) if changes in peak area metabolite ratios at magnetic resonance (MR) spectroscopy are associated with changes in T2 and fractional anisotropy (FA) at MR imaging. The local ethics committee approved this study, and informed parental consent was obtained for each infant. At term-equivalent age, 43 infants born at less than 32 weeks gestation underwent conventional and quantitative diffusion-tensor and T2-weighted MR imaging. Single-voxel point-resolved proton (hydrogen 1) MR spectroscopy was performed from a 2-cm(3) voxel centered in the posterior periventricular white matter. Outcome was evaluated by using Bayley scales at a corrected age of 1 year. Associations were investigated with Pearson product moment or Spearman rank order correlation. Differences in ratios in infants with and infants without impairment were tested by using t tests. NAA/Cho and Cho/Cr ratios correlated with the scaled gross motor score and the composite motor score, independent of gestational age (P NAA/Cho ratio (P NAA/Cho ratio (P NAA/Cho ratio predicted impaired motor outcome at a corrected age of 1 year with a sensitivity of 0.80 (95% confidence interval [CI]: 0.57, 0.94) and a specificity of 0.80 (95% CI: 0.66, 0.88). The combination of Cho/Cr and NAA/Cho ratios measured in the posterior periventricular white matter at term-equivalent age is predictive of motor outcome at 1 year in infants born at less than 32 weeks gestation. RSNA, 2013

Evaluation of persistence of resistant variants with ultra-deep pyrosequencing in chronic hepatitis C patients treated with telaprevir.

Directory of Open Access Journals (Sweden)

Xiomara V Thomas

Full Text Available BACKGROUND & AIMS: Telaprevir, a hepatitis C virus NS3/4A protease inhibitor has significantly improved sustained viral response rates when given in combination with pegylated interferon alfa-2a and ribavirin, compared with current standard of care in hepatitis C virus genotype 1 infected patients. In patients with a failed sustained response, the emergence of drug-resistant variants during treatment has been reported. It is unclear to what extent these variants persist in untreated patients. The aim of this study was to assess using ultra-deep pyrosequencing, whether after 4 years follow-up, the frequency of resistant variants is increased compared to pre-treatment frequencies following 14 days of telaprevir treatment. METHODS: Fifteen patients from 2 previous telaprevir phase 1 clinical studies (VX04-950-101 and VX05-950-103 were included. These patients all received telaprevir monotherapy for 14 days, and 2 patients subsequently received standard of care. Variants at previously well-characterized NS3 protease positions V36, T54, R155 and A156 were assessed at baseline and after a follow-up of 4±1.2 years by ultra-deep pyrosequencing. The prevalence of resistant variants at follow-up was compared to baseline. RESULTS: Resistance associated mutations were detectable at low frequency at baseline. In general, prevalence of resistance mutations at follow-up was not increased compared to baseline. Only one patient had a small, but statistically significant, increase in the number of V36M and T54S variants 4 years after telaprevir-dosing. CONCLUSION: In patients treated for 14 days with telaprevir monotherapy, ultra-deep pyrosequencing indicates that long-term persistence of resistant variants is rare.

Molecular Basis for Necitumumab Inhibition of EGFR Variants Associated with Acquired Cetuximab Resistance.

Science.gov (United States)

Bagchi, Atrish; Haidar, Jaafar N; Eastman, Scott W; Vieth, Michal; Topper, Michael; Iacolina, Michelle D; Walker, Jason M; Forest, Amelie; Shen, Yang; Novosiadly, Ruslan D; Ferguson, Kathryn M

2018-02-01

Acquired resistance to cetuximab, an antibody that targets the EGFR, impacts clinical benefit in head and neck, and colorectal cancers. One of the mechanisms of resistance to cetuximab is the acquisition of mutations that map to the cetuximab epitope on EGFR and prevent drug binding. We find that necitumumab, another FDA-approved EGFR antibody, can bind to EGFR that harbors the most common cetuximab-resistant substitution, S468R (or S492R, depending on the amino acid numbering system). We determined an X-ray crystal structure to 2.8 Å resolution of the necitumumab Fab bound to an S468R variant of EGFR domain III. The arginine is accommodated in a large, preexisting cavity in the necitumumab paratope. We predict that this paratope shape will be permissive to other epitope substitutions, and show that necitumumab binds to most cetuximab- and panitumumab-resistant EGFR variants. We find that a simple computational approach can predict with high success which EGFR epitope substitutions abrogate antibody binding. This computational method will be valuable to determine whether necitumumab will bind to EGFR as new epitope resistance variants are identified. This method could also be useful for rapid evaluation of the effect on binding of alterations in other antibody/antigen interfaces. Together, these data suggest that necitumumab may be active in patients who are resistant to cetuximab or panitumumab through EGFR epitope mutation. Furthermore, our analysis leads us to speculate that antibodies with large paratope cavities may be less susceptible to resistance due to mutations mapping to the antigen epitope. Mol Cancer Ther; 17(2); 521-31. ©2017 AACR . ©2017 American Association for Cancer Research.

Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance

Directory of Open Access Journals (Sweden)

Claire Jackson

2013-01-01

Full Text Available Overexpression of human epidermal growth factor receptor (HER-2 occurs in 20–30% of breast cancers and confers survival and proliferative advantages on the tumour cells making HER-2 an ideal therapeutic target for drugs like Herceptin. Continued delineation of tumour biology has identified splice variants of HER-2, with contrasting roles in tumour cell biology. For example, the splice variant 16HER-2 (results from exon 16 skipping increases transformation of cancer cells and is associated with treatment resistance; conversely, Herstatin (results from intron 8 retention and p100 (results from intron 15 retention inhibit tumour cell proliferation. This review focuses on the potential clinical implications of the expression and coexistence of HER-2 splice variants in cancer cells in relation to breast cancer progression and drug resistance. “Individualised” strategies currently guide breast cancer management; in accordance, HER-2 splice variants may prove valuable as future prognostic and predictive factors, as well as potential therapeutic targets.

Gene mutation, quantitative mutagenesis, and mutagen screening in mammalian cells: study with the CHO/HGPRT system

International Nuclear Information System (INIS)

Hsie, A.W.

1980-01-01

We have employed CHO cells to develop and define a set of stringent conditions for studying mutation induction to TG resistance. Several lines of evidence support the CHO/HGPRT system as a specific-locus mutational assay. The system permits quantification of mutation at the HGPRT locus induced by various physical and chemical mutagens. The quantitative nature of the system provides a basis for the study of structure-function relationships of various classes of chemical mutagens. The intra- and interlaboratory reproducibility of this system suggests its potential for screening environmental agents for mutagenic activity

Cadmium plating replacements

Energy Technology Data Exchange (ETDEWEB)

Nelson, M.J.; Groshart, E.C.

1995-03-01

The Boeing Company has been searching for replacements to cadmium plate. Two alloy plating systems seem close to meeting the needs of a cadmium replacement. The two alloys, zinc-nickel and tin-zinc are from alloy plating baths; both baths are neutral pH. The alloys meet the requirements for salt fog corrosion resistance, and both alloys excel as a paint base. Currently, tests are being performed on standard fasteners to compare zinc-nickel and tin-zinc on threaded hardware where cadmium is heavily used. The Hydrogen embrittlement propensity of the zinc-nickel bath has been tested, and just beginning for the tin-zinc bath. Another area of interest is the electrical properties on aluminum for tin-zinc and will be discussed. The zinc-nickel alloy plating bath is in production in Boeing Commercial Airplane Group for non-critical low strength steels. The outlook is promising that these two coatings will help The Boeing Company significantly reduce its dependence on cadmium plating.

Cadmium resistance in Drosophila: a small cadmium binding substance

International Nuclear Information System (INIS)

Jacobson, K.B.; Williams, M.W.; Richter, L.J.; Holt, S.E.; Hook, G.J.; Knoop, S.M.; Sloop, F.V.; Faust, J.B.

1985-01-01

A small cadmium-binding substance (CdBS) has been observed in adult Drosophila melanogaster that were raised for their entire growth cycle on a diet that contained 0.15 mM CdCl 2 . Induction of CdBS was observed in strains that differed widely in their sensitivity of CdCl 2 . This report describes the induction of CdBS and some of its characteristics. 17 refs., 4 figs., 1 tab

Organisation of Dietary Control for Nutrition-Training Intervention Involving Periodized Carbohydrate (CHO) Availability and Ketogenic Low CHO High Fat (LCHF) Diet.

Science.gov (United States)

Mirtschin, Joanne G; Forbes, Sara F; Cato, Louise E; Heikura, Ida A; Strobel, Nicki; Hall, Rebecca; Burke, Louise M

2018-02-12

We describe the implementation of a 3-week dietary intervention in elite race walkers at the Australian Institute of Sport, with a focus on the resources and strategies needed to accomplish a complex study of this scale. Interventions involved: traditional guidelines of high carbohydrate (CHO) availability for all training sessions (HCHO); a periodized CHO diet which integrated sessions with low CHO and high CHO availability within the same total CHO intake, and a ketogenic low-CHO high-fat diet (LCHF). 7-day menus and recipes were constructed for a communal eating setting to meet nutritional goals as well as individualized food preferences and special needs. Menus also included nutrition support pre, during and post-exercise. Daily monitoring, via observation and food checklists, showed that energy and macronutrient targets were achieved: diets were matched for energy (~14.8 MJ/d) and protein (~2.1 g.kg/d), and achieved desired differences for fat and CHO: HCHO and PCHO: CHO = 8.5 g/kg/d, 60% energy; fat = 20% of energy; LCHF: 0.5 g/kg/d CHO, fat = 78% energy. There were no differences in micronutrient intakes or density between HCHO and PCHO diets; however, the micronutrient density of LCHF was significantly lower. Daily food costs per athlete were similar for each diet (~AUDS$27 ± 10). Successful implementation and monitoring of dietary interventions in sports nutrition research of the scale of the present study require meticulous planning and the expertise of chefs and sports dietitians. Different approaches to sports nutrition support raise practical challenges around cost, micronutrient density, accommodation of special needs and sustainability.

Electro-spark machining of cadmium antimonide

International Nuclear Information System (INIS)

Ivanovskij, V.N.; Stepakhina, K.A.

1975-01-01

Experimental data on electrical erosion of the semiconductor material (cadmium antimonide) alloyed with tellurium are given. The potentialisies and expediency of using the electric-spark method of cutting cadmium antimonide ingots with the resistivity of 1 ohm is discussed. Cutting has been carried out in distilled water and in the air

Comparative genomics and drug resistance of a geographic variant of ST239 methicillin-resistant Staphylococcus aureus emerged in Russia.

Directory of Open Access Journals (Sweden)

Tatsuo Yamamoto

Full Text Available Two distinct classes of methicillin-resistant Staphylococcus aureus (MRSA are spreading in hospitals (as hospital-acquired MRSA, HA-MRSA and in the community (as community-acquired MRSA, CA-MRSA. Multilocus sequence type (ST 239 MRSA, one of the most worldwide-disseminated lineages, has been noted as a representative HA-MRSA. Here, we isolated ST239 MRSA (spa type 3 [t037] and staphylococcal cassette chromosome mec [SCCmec] type III.1.1.1 and its novel variant with ST239/spa351 (t030/SCCmecIII.1.1.4 (SCCmecIII(R not only from hospitals but also from patients with urethritis in the community in Russia. The Russian variant (strain 16K possessed a hybrid genome consisting of CC8 and CC30, similar to the ST239/spa3/SCCmecIII.1.1.1 HA-MRSA (TW20 genome, but with marked diversity. The 16K' CC30 section had SCCmecIII(R carrying the dcs-carrying unit (which corresponded to the SCCmecIVc J3 joining region of ST30 CA-MRSA, lacked SCCmercury, and possessed a novel mobile element structure (MES16K carrying the ccrC-carrying unit (with the recombinase gene ccrC1 allele 3 and drug resistance tranposons. The Russian variant included strains with a high ability to transfer its multiple drug resistance by conjugation; e.g., for strain 16K, the transfer frequency of a chloramphenicol resistance plasmid (p16K-1 with 2.9 kb in size reached 1.4×10(-2, followed by Tn554 conjugative transfer at 3.6×l0(-4. The Russian variant, which has been increasing recently, included divergent strains with different plasmid patterns and pulsed field gel electrophoresis profiles. The data demonstrate the alternative nature of ST239 MRSA as CA-MRSA and also as a drug resistance disseminator, and its micro but dynamic evolution in Russia.

Dicty_cDB: CHO774 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available m cDNA clone 58915 5', mRNA sequence. 42 13 1 DN493309 |DN493309.1 X077H09.3pR Populus wood cDNA library Populus tremula x Popul...CH (Link to library) CHO774 (Link to dictyBase) - - - Contig-U12145-1 - (Link to Or...iginal site) - - CHO774Z 618 - - - - Show CHO774 Library CH (Link to library) Clone ID CHO774 (Link to dicty...osome 3. 42 13 1 CV435371 |CV435371.1 58915.1 Suspension culture Solanum tuberosu...manei cDNA 5, mRNA sequence. 34 2.1 2 AP004054 |AP004054.3 Oryza sativa (japonica culti

Antibacterial efficacy of nisin, pediocin 34 and enterocin FH99 against L. monocytogenes, E. faecium and E. faecalis and bacteriocin cross resistance and antibiotic susceptibility of their bacteriocin resistant variants.

Science.gov (United States)

Kaur, Gurpreet; Singh, Tejinder Pal; Malik, Ravinder Kumar; Bhardwaj, Arun; De, Sachinandan

2014-02-01

The bacteriocin susceptibility of Listeria monocytogenes MTCC 657, Enterococcus faecium DSMZ 20477, E. faecium VRE, and E. faecalis ATCC 29212 and their corresponding bacteriocin resistant variants was assessed. The single and combined effect of nisin and pediocin 34 and enterocin FH99 bacteriocins produced by Pediococcus pentosaceus 34, and E. faecium FH99, respectively, was determined. Pediocin34 proved to be more effective in inhibiting L. monocytogenes MTCC 657. A greater antibacterial effect was observed against E. faecium DSMZ 20477 and E. faecium (VRE) when the a combination of nisin, pediocin 34 and enterocin FH99 were used whereas in case of L. monocytogenes MTCC 657 a combination of pediocin 34 and enterocin FH99 was more effective in reducing the survival of pathogen. Bacteriocin cross-resistance and the antibiotic susceptibility of wild type and their corresponding resistant variants were assessed and results showed that resistance to a bacteriocin may extend to other bacteriocins within the same class and also the acquired resistance to bacteriocins can modify the antibiotic susceptibility/resistance profile of the bacterial species used in the study. According to the hydrophobicity nisin resistant variant of L. monocytogenes was more hydrophobic (p enterocin FH99 resistant variants were less hydrophobic than the wild type strain. Nisin, pediocin 34 and enterocin FH99 resistant variants of E. faecium DSMZ 20477 and E. faecium VRE were less hydrophobic than their wild type counterparts. Nisin resistant E. faecalis ATCC 29212 was less hydrophobic than its wild type counterpart.

Irradiation and corrosion behaviour of cadmium aluminate, a burnable poison for light water reactors

International Nuclear Information System (INIS)

Hattenbach, K.; Ahlf, J.; Hilgendorff, W.; Zimmermann, H.U.

1979-01-01

In quest of a cadmium containing material for use as burnable poison cadmium aluminate seemed promising. Therefore irradiation and corrosion experiments on specimens of cadmium aluminate in a matrix of aluminia were performed. Irradiation at 575 K and fast fluences up to 10 25 m -2 showed the material to have good radiation resistance and low swelling rates. Cadmium pluminate was resistant to corrosion attack in demineralized water of 575K. (orig.) [de

A Study on the Fabrication of Uranium-Cadmium Alloy and its Distillation Behavior

International Nuclear Information System (INIS)

Kim, Ji Yong; Ahn, Do Hee; Kim, Kwang Rag; Paek, Seung Woo; Kim, Si Hyung

2010-01-01

The pyrometallurgical nuclear fuel recycle process, called pyroprocessing, has been known as a promising nuclear fuel recycling technology. Pyroprocessing technology is crucial to advanced nuclear systems due to increased nuclear proliferation resistance and economic efficiency. The basic concept of pyroprocessing is group actinide recovery, which enhances the nuclear proliferation resistance significantly. One of the key steps in pyroprocessing is 'electrowinning' which recovers group actinides with lanthanide from the spent nuclear fuels. In this study, a vertical cadmium distiller was manufactured. The evaporation rate of pure cadmium in vertical cadmium distiller varied from 12.3 to 40.8 g/cm 2 /h within a temperature range of 773 ∼ 923 K and pressure below 0.01 torr. Uranium - cadmium alloy was fabricated by electrolysis using liquid cadmium cathode in a high purity argon atmosphere glove box. The distillation behavior of pure cadmium and cadmium in uranium - cadmium alloy was investigated. The distillation behavior of cadmium from this study could be used to develop an actinide recovery process from a liquid cadmium cathode in a cadmium distiller

A Study on the Fabrication of Uranium-Cadmium Alloy and its Distillation Behavior

Energy Technology Data Exchange (ETDEWEB)

Kim, Ji Yong [University of Science and Technology, Daejeon (Korea, Republic of); Ahn, Do Hee; Kim, Kwang Rag; Paek, Seung Woo; Kim, Si Hyung [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2010-12-15

The pyrometallurgical nuclear fuel recycle process, called pyroprocessing, has been known as a promising nuclear fuel recycling technology. Pyroprocessing technology is crucial to advanced nuclear systems due to increased nuclear proliferation resistance and economic efficiency. The basic concept of pyroprocessing is group actinide recovery, which enhances the nuclear proliferation resistance significantly. One of the key steps in pyroprocessing is 'electrowinning' which recovers group actinides with lanthanide from the spent nuclear fuels. In this study, a vertical cadmium distiller was manufactured. The evaporation rate of pure cadmium in vertical cadmium distiller varied from 12.3 to 40.8 g/cm{sup 2}/h within a temperature range of 773 {approx} 923 K and pressure below 0.01 torr. Uranium - cadmium alloy was fabricated by electrolysis using liquid cadmium cathode in a high purity argon atmosphere glove box. The distillation behavior of pure cadmium and cadmium in uranium - cadmium alloy was investigated. The distillation behavior of cadmium from this study could be used to develop an actinide recovery process from a liquid cadmium cathode in a cadmium distiller.

Variants of β-lactamase KPC-2 that are resistant to inhibition by avibactam.

Science.gov (United States)

Papp-Wallace, Krisztina M; Winkler, Marisa L; Taracila, Magdalena A; Bonomo, Robert A

2015-07-01

KPC-2 is the most prevalent class A carbapenemase in the world. Previously, KPC-2 was shown to hydrolyze the β-lactamase inhibitors clavulanic acid, sulbactam, and tazobactam. In addition, substitutions at amino acid position R220 in the KPC-2 β-lactamase increased resistance to clavulanic acid. A novel bridged diazabicyclooctane (DBO) non-β-lactam β-lactamase inhibitor, avibactam, was shown to inactivate the KPC-2 β-lactamase. To better understand the mechanistic basis for inhibition of KPC-2 by avibactam, we tested the potency of ampicillin-avibactam and ceftazidime-avibactam against engineered variants of the KPC-2 β-lactamase that possessed single amino acid substitutions at important sites (i.e., Ambler positions 69, 130, 234, 220, and 276) that were previously shown to confer inhibitor resistance in TEM and SHV β-lactamases. To this end, we performed susceptibility testing, biochemical assays, and molecular modeling. Escherichia coli DH10B carrying KPC-2 β-lactamase variants with the substitutions S130G, K234R, and R220M demonstrated elevated MICs for only the ampicillin-avibactam combinations (e.g., 512, 64, and 32 mg/liter, respectively, versus the MICs for wild-type KPC-2 at 2 to 8 mg/liter). Steady-state kinetics revealed that the S130G variant of KPC-2 resisted inactivation by avibactam; the k2/K ratio was significantly lowered 4 logs for the S130G variant from the ratio for the wild-type enzyme (21,580 M(-1) s(-1) to 1.2 M(-1) s(-1)). Molecular modeling and molecular dynamics simulations suggested that the mobility of K73 and its ability to activate S70 (i.e., function as a general base) may be impaired in the S130G variant of KPC-2, thereby explaining the slowed acylation. Moreover, we also advance the idea that the protonation of the sulfate nitrogen of avibactam may be slowed in the S130G variant, as S130 is the likely proton donor and another residue, possibly K234, must compensate. Our findings show that residues S130 as well as K234 and R

Misonidazole-glutathione conjugates in CHO cells

International Nuclear Information System (INIS)

Varghese, A.J.; Whitmore, G.F.

1984-01-01

Misonidazole, after reduction to the hydroxylamine derivative, reacts with glutathione (GSH) under physiological conditions. The reaction product has been identified as a mixture of two isomeric conjugates. When water soluble extracts of CHO cells exposed to misonidazole under hypoxic conditions are subjected to HPLC analysis, misonidazole derivatives, having the same chromatographic properties as the GSH-MISO conjugates, were detected. When CHO cells were incubated with misonidazole in the presence of added GSH, a substantial increase in the amount of the conjugate was detected. When extracts of CHO cells exposed to misonidazole under hypoxia were subsequently exposed to GSH, an increased formation of the conjugate was observed. A rearrangement product of the hydroxylamine derivative of misonidazole is postulated as the reactive intermediate responsible for the formation of the conjugate

Murine strain differences and the effects of zinc on cadmium concentrations in tissues after acute cadmium exposure

Energy Technology Data Exchange (ETDEWEB)

King, L.M. [ARS USDA, Germplasm and Gamete Physiology Lab., Beltsville, MD (United States); Anderson, M.B. [Dept. of Anatomy, Tulane Univ. School of Medicine, New Orleans, LA (United States); Sikka, S.C. [Dept. of Urology, Tulane Univ. School of Medicine, New Orleans, LA (United States); George, W.J. [Dept. of Pharmacology, Tulane Univ. School of Medicine, New Orleans, LA (United States)

1998-10-01

The role of strain differences in cadmium tissue distribution was studied using sensitive (129/J) and resistant (A/J) mice. These murine strains have previously been shown to differ in their susceptibility to cadmium-induced testicular toxicity. Cadmium concentration was measured in testis, epididymis, seminal vesicle, liver, and kidney at 24 h after cadmium chloride exposure (4, 10, and 20 {mu}mol/kg CdCl{sub 2}). The 129/J mice exhibited a significant increase in cadmium concentration in testis, epididymis, and seminal vesicle at all cadmium doses used, compared to A/J mice. However, cadmium concentrations in liver and kidney were not different between the strains, at any dose, indicating that cadmium uptake is similar in these organs at 24 h. These murine strains demonstrate similar hepatic and renal cadmium uptake but significantly different cadmium accumulation in the reproductive organs at 24 h. The mechanism of the protective effect of zinc on cadmium toxicity was studied by assessing the impact of zinc acetate (ZnAc) treatment on cadmium concentrations in 129/J mice after 24 h. Zinc pretreatment (250 {mu}mol/kg ZnAc), given 24 h prior to 20 {mu}mol/kg CdCl{sub 2} administration, significantly decreased the amount of cadmium in the testis, epididymis, and seminal vesicle of 129/J mice, and significantly increased the cadmium content of the liver after 24 h. Cadmium levels in the kidney were unaffected at this time. Zinc pretreatment also prevented the cadmium-induced decrease in testicular sperm concentration and epididymal sperm motility seen in 129/J mice. These findings suggest that the differences in the two murine strains may be attributed partly to the differential accumulation of cadmium in murine gonads. This may be caused by strain differences in the specificity of cadmium transport mechanisms. The protective role of zinc in cadmium-induced testicular toxicity in the sensitive strain may be due to an interference in the cadmium uptake by susceptible

Enhanced lysosomal acidification leads to increased chloroquine accumulation in CHO cells expressing the pfmdr1 gene

NARCIS (Netherlands)

van Es, H. H.; Renkema, H.; Aerts, H.; Schurr, E.

1994-01-01

Expression of the pfmdr1-encoded Pgh1 protein of Plasmodium falciparum in CHO cells confers a phenotype of increased sensitivity to chloroquine due to an increased Pgh1-mediated accumulation of this antimalarial. Pgh1 carrying amino acid substitutions associated with chloroquine resistance in P.

Cadmium colours: composition and properties

International Nuclear Information System (INIS)

Paulus, J.; Knuutinen, U.

2004-01-01

The composition and the properties of cadmium aquarelle colours are discussed. The examined colours were 24 different aquarelle cadmium colours from six different manufacturers. The colours ranged from light, bright yellows to dark, deep-red tones. The aim of this research was to find out if the pigments contain cadmium salts: sulphides and/or selenides. This information will help in choosing watercolours in conservation processes. Today, aquarelle colours not containing cadmium pigments are being sold as cadmium colours; thus their properties might be different from actual cadmium colours. The aim of the research was to verify that the colour samples contained cadmium pigments and to estimate their compositions and ageing properties. Element analyses were performed from colour samples using micro-chemical tests and X-ray fluorescence measurements. Thin-layer chromatography was used for analysing gum Arabic as a possible binding medium in the chosen colour samples. Through ageing tests, the resistance of the colour samples to the exposure to light, heat and humidity was studied. Visible-light spectroscopy was used in determining the hues and hue changes of the aquarelle colour samples. The spectrophotometer used the CIE L * a * b * tone colour measuring system. From the colour measurements the changes in the lightness/darkness, the redness, the yellowness and the saturation of the samples were examined. (orig.)

Characterization of cadmium-resistant bacteria and their potential for reducing accumulation of cadmium in rice grains

International Nuclear Information System (INIS)

Lin, Xiaoyan; Mou, Renxiang; Cao, Zhaoyun; Xu, Ping; Wu, Xiaoliang; Zhu, Zhiwei; Chen, Mingxue

2016-01-01

Cadmium (Cd) pollution is a serious widespread environmental problem that not only destroys the microbial ecology of soil and decreases crop production, but also poses a serious risk to human health. Many methods have been used for the remediation of Cd pollution but none of these is totally satisfactory. Microbial remediation strategies have attracted increasing interest since they are environmentally friendly and cost-effective. In the present study, three Cd-resistant bacteria were isolated and evaluated for potential application in Cd bioremediation. Based on their morphological, physiological and biochemical characteristics, together with 16S rDNA gene sequence analyses, bacteria were identified as Stenotrophomonas acidaminiphila (2#), Pseudomonas aeruginosa (9#) and Delftia tsuruhatensis (12#). Pseudomonas aeruginosa showed very high tolerance to metals, especially Cd (2200 mg/L), Zn (1800 mg/L) and Pb (1200 mg/L), and is thought to be a multi-metal-resistant bacterium. Pseudomonas aeruginosa was also sensitive to 13 different antibiotics. The effects of the bacterial strains on the growth of rice plants and their ability to reduce Cd accumulation from Cd-contaminated soils in pot experiments were also evaluated. For Oryza sativa L. A grown in contaminated soil (3 mg/kg Cd), the accumulation of Cd was decreased by 31.2 and 25.5% in brown rice and polished rice, respectively, by strain 9#; Pseudomonas aeruginosa was more effective in reducing Cd accumulation in rice grains than a mixture of strains. For Oryza sativa L. B, a mixture of strains acting synergistically was more effective than a single strain in reducing Cd accumulation; treatment with mixed strains (strains + 3 mg/kg Cd) resulted in 41.3, 35.9, and 32.6% reductions in Cd accumulation in unhulled rice, brown rice and polished rice, respectively. Although different results were obtained for two rice varieties, it can still be concluded that Cd-resistant bacteria are suitable for reducing Cd

Characterization of cadmium-resistant bacteria and their potential for reducing accumulation of cadmium in rice grains

Energy Technology Data Exchange (ETDEWEB)

Lin, Xiaoyan; Mou, Renxiang; Cao, Zhaoyun; Xu, Ping; Wu, Xiaoliang; Zhu, Zhiwei; Chen, Mingxue, E-mail: cmingxue@126.com

2016-11-01

Cadmium (Cd) pollution is a serious widespread environmental problem that not only destroys the microbial ecology of soil and decreases crop production, but also poses a serious risk to human health. Many methods have been used for the remediation of Cd pollution but none of these is totally satisfactory. Microbial remediation strategies have attracted increasing interest since they are environmentally friendly and cost-effective. In the present study, three Cd-resistant bacteria were isolated and evaluated for potential application in Cd bioremediation. Based on their morphological, physiological and biochemical characteristics, together with 16S rDNA gene sequence analyses, bacteria were identified as Stenotrophomonas acidaminiphila (2#), Pseudomonas aeruginosa (9#) and Delftia tsuruhatensis (12#). Pseudomonas aeruginosa showed very high tolerance to metals, especially Cd (2200 mg/L), Zn (1800 mg/L) and Pb (1200 mg/L), and is thought to be a multi-metal-resistant bacterium. Pseudomonas aeruginosa was also sensitive to 13 different antibiotics. The effects of the bacterial strains on the growth of rice plants and their ability to reduce Cd accumulation from Cd-contaminated soils in pot experiments were also evaluated. For Oryza sativa L. A grown in contaminated soil (3 mg/kg Cd), the accumulation of Cd was decreased by 31.2 and 25.5% in brown rice and polished rice, respectively, by strain 9#; Pseudomonas aeruginosa was more effective in reducing Cd accumulation in rice grains than a mixture of strains. For Oryza sativa L. B, a mixture of strains acting synergistically was more effective than a single strain in reducing Cd accumulation; treatment with mixed strains (strains + 3 mg/kg Cd) resulted in 41.3, 35.9, and 32.6% reductions in Cd accumulation in unhulled rice, brown rice and polished rice, respectively. Although different results were obtained for two rice varieties, it can still be concluded that Cd-resistant bacteria are suitable for reducing Cd

Nonradioactive heteroduplex tracking assay for the detection of minority-variant chloroquine-resistant Plasmodium falciparum in Madagascar

Science.gov (United States)

Juliano, Jonathan J; Randrianarivelojosia, Milijaona; Ramarosandratana, Benjamin; Ariey, Frédéric; Mwapasa, Victor; Meshnick, Steven R

2009-01-01

Background Strains of Plasmodium falciparum genetically resistant to chloroquine (CQ) due to the presence of pfcrt 76T appear to have been recently introduced to the island of Madagascar. The prevalence of such resistant genotypes is reported to be low (chloroquine resistant parasites were described in Malawian patients using an isotopic heteroduplex tracking assay (HTA), which can detect pfcrt 76T-bearing P. falciparum minority variants in individual patients that were undetectable by conventional PCR. However, as this assay required a radiolabeled probe, it could not be used in many resource-limited settings. Methods This study describes a digoxigenin (DIG)-labeled chemiluminescent heteroduplex tracking assay (DIG-HTA) to detect pfcrt 76T-bearing minority variant P. falciparum. This assay was compared to restriction fragment length polymorphism (RFLP) analysis and to the isotopic HTA for detection of genetically CQ-resistant parasites in clinical samples. Results Thirty one clinical P. falciparum isolates (15 primary isolates and 16 recurrent isolates) from 17 Malagasy children treated with CQ for uncomplicated malaria were genotyped for the pfcrt K76T mutation. Two (11.7%) of 17 patients harboured genetically CQ-resistant P. falciparum strains after therapy as detected by HTA. RFLP analysis failed to detect any pfcrt K76T-bearing isolates. Conclusion These findings indicate that genetically CQ-resistant P. falciparum are more common than previously thought in Madagascar even though the fitness of the minority variant pfcrt 76T parasites remains unclear. In addition, HTAs for malaria drug resistance alleles are promising tools for the surveillance of anti-malarial resistance. The use of a non-radioactive label allows for the use of HTAs in malaria endemic countries. PMID:19291288

Isolation, identification, characterization, and evaluation of cadmium removal capacity of Enterobacter species.

Science.gov (United States)

Abbas, Syed Zaghum; Rafatullah, Mohd; Ismail, Norli; Lalung, Japareng

2014-12-01

This study focused on the isolation and characterization of high cadmium-resistant bacterial strains, possible exploitation of its cadmium-accumulation and cadmium-induced proteins. Cadmium-resistant bacterial strains designated as RZ1 and RZ2 were isolated from industrial wastewater of Penang, Malaysia. These isolates were identified as Enterobacter mori and Enterobacter sp. WS12 on the basis of phenotypic, biochemical and 16S rDNA sequence based molecular phylogenetic characteristics. Both isolates were Gram negative, cocci, and growing well in Lauria-Bertani broth medium at 35 °C temperature and pH 7.0. Results also indicated that Enterobacter mori and Enterobacter sp. WS12are capable to remove 87.75 and 85.11% of the cadmium from 100 µg ml(-1) concentration, respectively. This study indicates that these strains can be useful as an inexpensive and efficient bioremediation technology to remove and recover the cadmium from wastewater. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Adaptive and cross-protective responses against cadmium and zinc toxicity in cadmium-resistant bacterium isolated from a zinc mine

Directory of Open Access Journals (Sweden)

Benjaphorn Prapagdee

2009-12-01

Full Text Available Cadmium (Cd is a major environmental hazard, which usually is detected in its ionic form of Cd2+. It also causes adverse toxic effects on human health and other living organisms. Cd-resistant bacteria were isolated from Cd-contaminated soils. One isolate, TAK1, was highly resistance level to Cd toxicity. TAK1 was isolated from soil contaminated with a high Cd concentration (204.1 mg.kg-1. The result of 16S rDNA sequence analysis found that the TAK1 showed the similarity to Ralstonia sp. Physiological adaptive and cross-protective responses to Cd and Zn killing were investigated in Ralstonia sp.TAK1. Exposure to a low concentration of Cd induced adaptive resistance to higher concentrations of Cd. In addition, pretreatment of Ralstonia sp.TAK1 with an inducing concentration of Cd conferred cross-protective response against subsequent exposure to the lethal concentrations of Zn. The induced adaptive and cross-protective response Ralstonia sp.TAK1 required newly synthesized protein(s. Cd-induced adaptive and cross-protective responses against Cd and Zn toxicity are the important mechanisms used by Ralstonia sp.TAK1 to survive in the heavy metal contaminated environments. These findings might lead to the use of Ralstonia sp.TAK1 for microbial based remediation in Cd and Zn-contaminated soils.

Glycoengineering of CHO Cells to Improve Product Quality.

Science.gov (United States)

Wang, Qiong; Yin, Bojiao; Chung, Cheng-Yu; Betenbaugh, Michael J

2017-01-01

Chinese hamster ovary (CHO) cells represent the predominant platform in biopharmaceutical industry for the production of recombinant biotherapeutic proteins, especially glycoproteins. These glycoproteins include oligosaccharide or glycan attachments that represent one of the principal components dictating product quality. Especially important are the N-glycan attachments present on many recombinant glycoproteins of commercial interest. Furthermore, altering the glycan composition can be used to modulate the production quality of a recombinant biotherapeutic from CHO and other mammalian hosts. This review first describes the glycosylation network in mammalian cells and compares the glycosylation patterns between CHO and human cells. Next genetic strategies used in CHO cells to modulate the sialylation patterns through overexpression of sialyltransfereases and other glycosyltransferases are summarized. In addition, other approaches to alter sialylation including manipulation of sialic acid biosynthetic pathways and inhibition of sialidases are described. Finally, this review also covers other strategies such as the glycosylation site insertion and manipulation of glycan heterogeneity to produce desired glycoforms for diverse biotechnology applications.

Acquired tolerance in cadmium-adapted lung epithelial cells: Roles of the c-Jun N-terminal kinase signaling pathway and basal level of metallothionein

International Nuclear Information System (INIS)

Lau, Andy T.Y.; Zhang Jian; Chiu, J.-F.

2006-01-01

Cadmium-resistant cells were developed in our laboratory with rat lung epithelial cells (LECs) by stepwise exposure of LECs to cadmium chloride from 1 μM to 20 μM after 20 passages. To investigate the Cd-resistant phenotype in a long-term perspective, cadmium-resistant cells adapted to 20 μM cadmium (Cd R ) were then cultured in the absence of cadmium for various passages [Cd R (-n)]. All these adapted cells were significantly protected from cadmium toxicity as compared to parental cadmium-sensitive LECs (Cd S ). The cadmium-resistant phenotype of adapted cells was relatively stable in the absence of cadmium for as long as 40 passages. Basal mRNA level of metallothionein-1 (MT-1) was dramatically higher in Cd R than in Cd R (-), which may account for the higher Cd-resistance of Cd R than Cd R (-). MT-1 mRNA level decreased drastically in Cd R after cadmium removal, suggesting that the high basal level of MT-1 in Cd R may be only partially responsible for cadmium-resistance. Treatment of cells with high levels of cadmium resulted in decreased phosphorylation of c-Jun N-terminal kinase (JNK1/2) in adapted cells than in sensitive cells and this cadmium-induced JNK activity was blocked by JNK inhibitor II, SP600125. Ro318220, a strong activator of JNK, reverted cadmium-sensitive phenotype in adapted cells. Taken together, our results suggest that during cadmium adaptation, cells develop tolerance to cell death, generally due to perturbation of the JNK signaling pathway and the nonresponsiveness of JNK phosphorylation is critical for the Cd-tolerance in these cells

Cadmium-binding proteins in midgut gland of freshwater crayfish Procambarus clarkii

Energy Technology Data Exchange (ETDEWEB)

Del Ramo, J.; Pastor, A.; Torreblanca, A.; Medina, J.; Diza-Mayans, J.

1989-02-01

Metallothioneins, metal binding proteins, were originally isolated and characterized by Margoshes and Vallee. These proteins have a high affinity for various heavy metals, particularly cadmium and mercury and have extensively been studied in mammals. Metal binding proteins have been observed in a variety of marine invertebrates; however, there is very little information available on metal binding proteins in freshwater invertebrates, and particularly in freshwater crustaceans. Cadmium is an ubiquitous non essential element which possesses high toxicity to aquatic organisms. Cadmium binding proteins observed in invertebrates have similar characteristics to mammalian metallothioneins. In 1978, the American red crayfish appeared in Albufera Lake and the surrounding rice fields (Valencia, Spain). Albufera Lake and the surrounding rice fields waters are subjected to very heavy loads of sewage and toxic industrial residues (including heavy metals) from the many urban and wastewaters in this area. In previous reports the authors studied the toxicity and accumulation of cadmium on Procambarus clarkii of Albufera Lake. This crayfish shows a high resistance to cadmium and a great accumulation rate of this metal in several tissues, including midgut gland. Since Procambarus clarkii shows a high resistance to cadmium, the presence of cadmium binding proteins (Cd-BP) in midgut gland of these crayfish would be expected. This report describes results on the characterization of Cd-BPs obtained from cadmium exposed crayfish Procambarus clarkii, demonstrating their presence in this freshwater crayfish.

Recombination activating activity of XRCC1 analogous genes in X-ray sensitive and resistant CHO cell lines

International Nuclear Information System (INIS)

Golubnitchaya-Labudova, O.; Hoefer, M.; Portele, A.; Vacata, V.; Rink, H.; Lubec, G.

1997-01-01

The XRCC1 gene (X-ray repair cross complementing) complements the DNA repair deficiency of the radiation sensitive Chinese hamster ovary (CHO) mutant cell line EM9 but the mechanism of the correction is not elucidated yet. XRCC1 shows substantial homology to the RAG2 gene (recombination activating gene) and we therefore tried to answer the question, whether structural similarities (sequence of a putative recombination activating domain, aa 332-362 for XRCC1 and aa 286-316 in RAG2) would reflect similar functions of the homologous, putative recombination activating domain. PCR experiments revealed that no sequence homologous to the structural part of human XRCC1 was present in cDNA of CHO. Differential display demonstrated two putative recombination activating in the parental CHO line AA8 and one in the radiosensitive mutant EM9. Southern blot experiments showed the presence of several genes with partial homology to human XRCC1. Recombination studies consisted of expressing amplified target domains within chimeric proteins in recA - bacteria and subsequent detection of recombination events by sequencing the recombinant plasmids. Recombination experiments demonstrated recombination activating activity of all putative recombination activating domains amplified from AA8 and EM9 genomes as reflected by deletions within the inserts of the recombinant plasmids. The recombination activating activity of XRCC1 analogues could explain a mechanism responsible for the correction of the DNA repair defect in EM9. (author)

Simultaneous determination of oxygen and cadmium in cadmium and cadmium compounds

International Nuclear Information System (INIS)

Imaeda, K.; Kuriki, T.; Ohsawa, K.; Ishii, Y.

1977-01-01

Cadmium and its compounds were analysed for oxygen and cadmium by a modification of the Schutze-Unterzaucher method. Oxygen in some compounds such as cadmium oxide, nitrate and sulphate could not be determined by the usual method. The method of adding carbon was employed for the determination of total oxygen. Total oxygen could be determined by the addition of 5 mg of carbon to a sample boat and heating at 950 0 . The determination was also carried out by addition of naphthalene (2 mg). It was found that the cadmium powder and cadmium flake used contained ca. 1 and 0.15% oxygen, respectively. Oxygen and cadmium in cadmium and its compounds were simultaneously determined by the addition of 2 mg of naphthalene. Cadmium was determined colorimetrically by use of glyoxal-bis-(2-hydroxyanil). Oxygen and cadmium in the samples could be determined simultaneously with an average error of -0.02 and -0.22%, respectively. (author)

The Products of the Thermal Decomposition of CH3CHO

Energy Technology Data Exchange (ETDEWEB)

Vasiliou, AnGayle; Piech, Krzysztof M.; Zhang, Xu; Nimlos, Mark R.; Ahmed, Musahid; Golan, Amir; Kostko, Oleg; Osborn, David L.; Daily, John W.; Stanton, John F.; Ellison, G. Barney

2011-04-06

We have used a heated 2 cm x 1 mm SiC microtubular (mu tubular) reactor to decompose acetaldehyde: CH3CHO + DELTA --> products. Thermal decomposition is followed at pressures of 75 - 150 Torr and at temperatures up to 1700 K, conditions that correspond to residence times of roughly 50 - 100 mu sec in the mu tubular reactor. The acetaldehyde decomposition products are identified by two independent techniques: VUV photoionization mass spectroscopy (PIMS) and infrared (IR) absorption spectroscopy after isolation in a cryogenic matrix. Besides CH3CHO, we have studied three isotopologues, CH3CDO, CD3CHO, and CD3CDO. We have identified the thermal decomposition products CH3(PIMS), CO (IR, PIMS), H (PIMS), H2 (PIMS), CH2CO (IR, PIMS), CH2=CHOH (IR, PIMS), H2O (IR, PIMS), and HC=CH (IR, PIMS). Plausible evidence has been found to support the idea that there are at least three different thermal decomposition pathways for CH3CHO: Radical decomposition: CH3CHO + DELTA --> CH3 + [HCO] --> CH3 + H + CO Elimination: CH3CHO + DELTA --> H2 + CH2=C=O. Isomerization/elimination: CH3CHO + DELTA --> [CH2=CH-OH] --> HC=CH + H2O. Both PIMS and IR spectroscopy show compelling evidence for the participation of vinylidene, CH2=C:, as an intermediate in the decomposition of vinyl alchohol: CH2=CH-OH + DELTA --> [CH2=C:] + H2O --> HC=CH + H2O.

Accumulation of MxB/Mx2-resistant HIV-1 Capsid Variants During Expansion of the HIV-1 Epidemic in Human Populations.

Science.gov (United States)

Wei, Wei; Guo, Haoran; Ma, Min; Markham, Richard; Yu, Xiao-Fang

2016-06-01

Recent studies have identified human myxovirus resistance protein 2 (MxB or Mx2) as an interferon induced inhibitor of HIV-1 replication. However, whether HIV-1 can overcome MxB restriction without compromise of viral fitness has been undefined. Here, we have discovered that naturally occurring capsid (CA) variants can render HIV-1 resistant to the activity of MxB without losing viral infectivity or the ability to escape from interferon induction. Moreover, these MxB resistant HIV-1 variants do not lose MxB recognition. Surprisingly, MxB resistant CA variants are most commonly found in the Clade C HIV-1 that is the most rapidly expanding Clade throughout the world. Accumulation of MxB resistant mutations is also observed during HIV-1 spreading in human populations. These findings support a potential role for MxB as a selective force during HIV-1 transmission and evolution. Copyright © 2016. Published by Elsevier B.V.

Identification of a novel vga(E) gene variant that confers resistance to pleuromutilins, lincosamides and streptogramin A antibiotics in staphylococci of porcine origin.

Science.gov (United States)

Li, Jun; Li, Beibei; Wendlandt, Sarah; Schwarz, Stefan; Wang, Yang; Wu, Congming; Ma, Zhiyong; Shen, Jianzhong

2014-04-01

To investigate the genetic basis of pleuromutilin resistance in coagulase-negative staphylococci of porcine origin that do not carry known pleuromutilin resistance genes and to determine the localization and genetic environment of the identified resistance gene. Plasmid DNA of two pleuromutilin-resistant Staphylococcus cohnii and Staphylococcus simulans isolates was transformed into Staphylococcus aureus RN4220. The identified resistance plasmids were sequenced completely. The candidate gene for pleuromutilin resistance was cloned into shuttle vector pAM401. S. aureus RN4220 transformants carrying this recombinant shuttle vector were tested for their MICs. S. cohnii isolate SA-7 and S. simulans isolate SSI1 carried the same plasmid of 5584 bp, designated pSA-7. A variant of the vga(E) gene was detected, which encodes a 524 amino acid ATP-binding cassette protein. The variant gene shared 85.7% nucleotide sequence identity and the variant protein 85.3% amino acid sequence identity with the original vga(E) gene and Vga(E) protein, respectively. The Vga(E) variant conferred cross-resistance to pleuromutilins, lincosamides and streptogramin A antibiotics. Plasmid pSA-7 showed an organization similar to that of the apmA-carrying plasmid pKKS49 from methicillin-resistant S. aureus and the dfrK-carrying plasmid pKKS966 from Staphylococcus hyicus. Sequence comparisons suggested that recombination events may have played a role in the acquisition of this vga(E) variant. A novel vga(E) gene variant was identified, which was located on a small plasmid and was not associated with the transposon Tn6133 [in contrast to the original vga(E) gene]. The plasmid location may enable its further dissemination to other staphylococci and possibly also to other bacteria.

Glycoengineering in CHO cells: Advances in systems biology

DEFF Research Database (Denmark)

Tejwani, Vijay; Andersen, Mikael Rørdam; Nam, Jong Hyun

2018-01-01

are not well understood. A systems biology approach combining different technologies is needed for complete understanding of the molecular processes accounting for this variability and to open up new venues in cell line development. In this review, we describe several advances in genetic manipulation, modeling......For several decades, glycoprotein biologics have been successfully produced from Chinese hamster ovary (CHO) cells. The therapeutic efficacy and potency of glycoprotein biologics are often dictated by their post translational modifications, particularly glycosylation, which unlike protein synthesis....... Recently, CHO cells have also been explored for production of therapeutic glycosaminoglycans (e.g. heparin), which presents similar challenges as producing glycoproteins biologics. Approaches to controlling heterogeneity in CHO cells and directing the biosynthetic process toward desired glycoforms...

Deep sequencing reveals different compositions of mRNA transcribed from the F8 gene in a panel of FVIII-producing CHO cell lines

DEFF Research Database (Denmark)

Kaas, Christian Schrøder; Bolt, Gert; Hansen, Jens J

2015-01-01

orders of magnitude lower than for antibodies. In the present study we investigated CHO DXB11 cells transfected with a plasmid encoding human coagulation factor VIII. Single cell clones were isolated from the pool of transfectants and a panel of 14 clones representing a dynamic range of FVIII...... FVIII productivity. It was found that three MTX resistant, nonproducing clones had different truncations of the F8 transcripts. We find that by using deep sequencing, in contrast to microarray technology, for determining the transcriptome from CHO transfectants, we are able to accurately deduce...

Characterization of cadmium-resistant bacteria and their potential for reducing accumulation of cadmium in rice grains.

Science.gov (United States)

Lin, Xiaoyan; Mou, Renxiang; Cao, Zhaoyun; Xu, Ping; Wu, Xiaoliang; Zhu, Zhiwei; Chen, Mingxue

2016-11-01

Cadmium (Cd) pollution is a serious widespread environmental problem that not only destroys the microbial ecology of soil and decreases crop production, but also poses a serious risk to human health. Many methods have been used for the remediation of Cd pollution but none of these is totally satisfactory. Microbial remediation strategies have attracted increasing interest since they are environmentally friendly and cost-effective. In the present study, three Cd-resistant bacteria were isolated and evaluated for potential application in Cd bioremediation. Based on their morphological, physiological and biochemical characteristics, together with 16S rDNA gene sequence analyses, bacteria were identified as Stenotrophomonas acidaminiphila (2#), Pseudomonas aeruginosa (9#) and Delftia tsuruhatensis (12#). Pseudomonas aeruginosa showed very high tolerance to metals, especially Cd (2200mg/L), Zn (1800mg/L) and Pb (1200mg/L), and is thought to be a multi-metal-resistant bacterium. Pseudomonas aeruginosa was also sensitive to 13 different antibiotics. The effects of the bacterial strains on the growth of rice plants and their ability to reduce Cd accumulation from Cd-contaminated soils in pot experiments were also evaluated. For Oryza sativa L. A grown in contaminated soil (3mg/kg Cd), the accumulation of Cd was decreased by 31.2 and 25.5% in brown rice and polished rice, respectively, by strain 9#; Pseudomonas aeruginosa was more effective in reducing Cd accumulation in rice grains than a mixture of strains. For Oryza sativa L. B, a mixture of strains acting synergistically was more effective than a single strain in reducing Cd accumulation; treatment with mixed strains (strains+3mg/kg Cd) resulted in 41.3, 35.9, and 32.6% reductions in Cd accumulation in unhulled rice, brown rice and polished rice, respectively. Although different results were obtained for two rice varieties, it can still be concluded that Cd-resistant bacteria are suitable for reducing Cd accumulation in

Cadmium ban spurs interest in zinc-nickel coating for corrosive aerospace environments

Energy Technology Data Exchange (ETDEWEB)

Bates, J. (Pure Coatings Inc., West Palm Beach, FL (United States))

1994-02-01

OSHA recently reduced the permissible exposure level for cadmium. The new standard virtually outlaws cadmium production and use, except in the most cost-insensitive applications. Aerospace manufacturers, which use cadmium extensively in coatings applications because of the material's corrosion resistance, are searching for substitutes. The most promising alternative found to date is a zinc-nickel alloy. Tests show that the alloy outperforms cadmium without generating associated toxicity issues. As a result, several major manufacturing and standards organizations have adopted the zinc-nickel compound as a standard cadmium replacement. The basis for revising the cadmium PEL -- which applies to occupational exposure in industrial, agricultural and maritime occupations -- is an official OSHA determination that employees exposed to cadmium under the existing PEL face significant health risks from lung cancer and kidney damage. In one of its principal uses, cadmium is electroplated to steel, where it acts as an anticorrosive agent.

Minor drug-resistant HIV type-1 variants in breast milk and plasma of HIV type-1-infected Ugandan women after nevirapine single-dose prophylaxis.

Science.gov (United States)

Pilger, Daniel; Hauser, Andrea; Kuecherer, Claudia; Mugenyi, Kizito; Kabasinguzi, Rose; Somogyi, Sybille; Harms, Gundel; Kunz, Andrea

2011-01-01

Nevirapine single-dose (NVP-SD) reduces mother-to-child transmission of HIV type-1 (HIV-1), but frequently induces resistance mutations in the HIV-1 genome. Little is known about drug-resistant HIV-1 variants in the breast milk of women who have taken NVP-SD. Blood and breast milk samples of 39 HIV-1-infected Ugandan women were taken 6-12 weeks after NVP-SD intake. Samples were analysed by population sequencing and allele-specific real-time PCR (AS-PCR) with detection limits for NVP-resistant HIV-1 variants (K103N and Y181C) of D n = 5, G n = 2 and C n = 1). A total of 7 (37%) and 10 (53%) women carried NVP-resistant virus in breast milk and plasma, respectively. Overall, 71% (5/7) women with NVP-resistant HIV-1 in breast milk displayed >1 drug-resistant variant. Resistance in breast milk was higher at week 6 (6/13 samples [46%]) compared with week 12 (1/6 samples [17%]). In total, 10 drug-resistant populations harbouring the K103N and/or Y181C mutation were detected in the 19 breast milk samples; 7 (70%) were caused by resistant minorities (< 5% of the total HIV-1 population). In the four women with drug-resistant virus in both plasma and breast milk, the mutation patterns differed between the two compartments. Minor populations of drug-resistant HIV-1 were frequently found in breast milk of Ugandan women after exposure to NVP-SD. Further studies need to explore the role of minor drug-resistant variants in the postnatal transmission of (resistant) HIV-1.

Cadmium carcinogenesis

International Nuclear Information System (INIS)

Waalkes, Michael P.

2003-01-01

Cadmium is a heavy metal of considerable environmental and occupational concern. Cadmium compounds are classified as human carcinogens by several regulatory agencies. The most convincing data that cadmium is carcinogenic in humans comes from studies indicating occupational cadmium exposure is associated with lung cancer. Cadmium exposure has also been linked to human prostate and renal cancer, although this linkage is weaker than for lung cancer. Other target sites of cadmium carcinogenesis in humans, such as liver, pancreas and stomach, are considered equivocal. In animals, cadmium effectively induces cancers at multiple sites and by various routes. Cadmium inhalation in rats induces pulmonary adenocarcinomas, in accord with its role in human lung cancer. Cadmium can induce tumors and/or preneoplastic lesions within the rat prostate after ingestion or injection. At relatively high doses, cadmium induces benign testicular tumors in rats, but these appear to be due to early toxic lesions and loss of testicular function, rather than from a specific carcinogenic effect of cadmium. Like many other metals, cadmium salts will induce mesenchymal tumors at the site of subcutaneous (s.c.) or intramuscular (i.m.) injections, but the human relevance of these is dubious. Other targets of cadmium in rodents include the liver, adrenal, pancreas, pituitary, and hematopoietic system. With the exception of testicular tumors in rodents, the mechanisms of cadmium carcinogenesis are poorly defined. Cadmium can cause any number of molecular lesions that would be relevant to oncogenesis in various cellular model systems. Most studies indicate cadmium is poorly mutagenic and probably acts through indirect or epigenetic mechanisms, potentially including aberrant activation of oncogenes and suppression of apoptosis

Cadmium carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Waalkes, Michael P

2003-12-10

Cadmium is a heavy metal of considerable environmental and occupational concern. Cadmium compounds are classified as human carcinogens by several regulatory agencies. The most convincing data that cadmium is carcinogenic in humans comes from studies indicating occupational cadmium exposure is associated with lung cancer. Cadmium exposure has also been linked to human prostate and renal cancer, although this linkage is weaker than for lung cancer. Other target sites of cadmium carcinogenesis in humans, such as liver, pancreas and stomach, are considered equivocal. In animals, cadmium effectively induces cancers at multiple sites and by various routes. Cadmium inhalation in rats induces pulmonary adenocarcinomas, in accord with its role in human lung cancer. Cadmium can induce tumors and/or preneoplastic lesions within the rat prostate after ingestion or injection. At relatively high doses, cadmium induces benign testicular tumors in rats, but these appear to be due to early toxic lesions and loss of testicular function, rather than from a specific carcinogenic effect of cadmium. Like many other metals, cadmium salts will induce mesenchymal tumors at the site of subcutaneous (s.c.) or intramuscular (i.m.) injections, but the human relevance of these is dubious. Other targets of cadmium in rodents include the liver, adrenal, pancreas, pituitary, and hematopoietic system. With the exception of testicular tumors in rodents, the mechanisms of cadmium carcinogenesis are poorly defined. Cadmium can cause any number of molecular lesions that would be relevant to oncogenesis in various cellular model systems. Most studies indicate cadmium is poorly mutagenic and probably acts through indirect or epigenetic mechanisms, potentially including aberrant activation of oncogenes and suppression of apoptosis.

A Potential Food-Grade Cloning Vector for Streptococcus thermophilus That Uses Cadmium Resistance as the Selectable Marker

OpenAIRE

Wong, Wing Yee; Su, Ping; Allison, Gwen E.; Liu, Chun-Qiang; Dunn, Noel W.

2003-01-01

A potential food-grade cloning vector, pND919, was constructed and transformed into S. thermophilus ST3-1, a plasmid-free strain. The vector contains DNAs from two different food-approved organisms, Streptococcus thermophilus and Lactococcus lactis. The 5.0-kb pND919 is a derivative of the cloning vector pND918 (9.3 kb) and was constructed by deletion of the 4.3-kb region of pND918 which contained DNA from non-food-approved organisms. pND919 carries a heterologous native cadmium resistance se...

Cadmium and Cadmium/Zinc Ratios and Tobacco-Related Morbidities

Science.gov (United States)

Richter, Patricia; Faroon, Obaid; Pappas, R. Steven

2017-01-01

Metals are one of five major categories of carcinogenic or toxic constituents in tobacco and tobacco smoke. Cadmium is highly volatile and a higher percentage of the total tobacco cadmium content is efficiently transferred to mainstream tobacco smoke than many other toxic metals in tobacco. Inhaled cadmium bioaccumulates in the lungs and is distributed beyond the lungs to other tissues, with a total body biological half-life of one to two decades. Chronic cadmium exposure through tobacco use elevates blood and urine cadmium concentrations. Cadmium is a carcinogen, and an inducer of proinflammatory immune responses. Elevated exposure to cadmium is associated with reduced pulmonary function, obstructive lung disease, bronchogenic carcinoma, cardiovascular diseases including myocardial infarction, peripheral arterial disease, prostate cancer, cervical cancer, pancreatic cancer, and various oral pathologies. Cadmium and zinc have a toxicologically inverse relationship. Zinc is an essential element and is reportedly antagonistic to some manifestations of cadmium toxicity. This review summarizes associations between blood, urine, and tissue cadmium concentrations with emphasis on cadmium exposure due to tobacco use and several disease states. Available data about zinc and cadmium/zinc ratios and tobacco-related diseases is summarized from studies reporting smoking status. Collectively, data suggest that blood, urine, and tissue cadmium and cadmium/zinc ratios are often significantly different between smokers and nonsmokers and they are also different in smokers for several diseases and cancers. Additional biomonitoring data such as blood or serum and urine zinc and cadmium levels and cadmium/zinc ratios in smokers may provide further insight into the development and progression of diseases of the lung, cardiovascular system, and possibly other organs. PMID:28961214

Cadmium and Cadmium/Zinc Ratios and Tobacco-Related Morbidities.

Science.gov (United States)

Richter, Patricia; Faroon, Obaid; Pappas, R Steven

2017-09-29

Metals are one of five major categories of carcinogenic or toxic constituents in tobacco and tobacco smoke. Cadmium is highly volatile and a higher percentage of the total tobacco cadmium content is efficiently transferred to mainstream tobacco smoke than many other toxic metals in tobacco. Inhaled cadmium bioaccumulates in the lungs and is distributed beyond the lungs to other tissues, with a total body biological half-life of one to two decades. Chronic cadmium exposure through tobacco use elevates blood and urine cadmium concentrations. Cadmium is a carcinogen, and an inducer of proinflammatory immune responses. Elevated exposure to cadmium is associated with reduced pulmonary function, obstructive lung disease, bronchogenic carcinoma, cardiovascular diseases including myocardial infarction, peripheral arterial disease, prostate cancer, cervical cancer, pancreatic cancer, and various oral pathologies. Cadmium and zinc have a toxicologically inverse relationship. Zinc is an essential element and is reportedly antagonistic to some manifestations of cadmium toxicity. This review summarizes associations between blood, urine, and tissue cadmium concentrations with emphasis on cadmium exposure due to tobacco use and several disease states. Available data about zinc and cadmium/zinc ratios and tobacco-related diseases is summarized from studies reporting smoking status. Collectively, data suggest that blood, urine, and tissue cadmium and cadmium/zinc ratios are often significantly different between smokers and nonsmokers and they are also different in smokers for several diseases and cancers. Additional biomonitoring data such as blood or serum and urine zinc and cadmium levels and cadmium/zinc ratios in smokers may provide further insight into the development and progression of diseases of the lung, cardiovascular system, and possibly other organs.

Effects of copper on CHO cells: cellular requirements and product quality considerations.

Science.gov (United States)

Yuk, Inn H; Russell, Stephen; Tang, Yun; Hsu, Wei-Ting; Mauger, Jacob B; Aulakh, Rigzen P S; Luo, Jun; Gawlitzek, Martin; Joly, John C

2015-01-01

Recent reports highlight the impact of copper on lactate metabolism: CHO cell cultures with higher initial copper levels shift to net lactate consumption and yield lower final lactate and higher titers. These studies investigated the effects of copper on metabolite and transcript profiles, but did not measure in detail the dependences of cell culture performance and product quality on copper concentrations. To more thoroughly map these dependences, we explored the effects of various copper treatments on four recombinant CHO cell lines. In the first cell line, when extracellular copper remained above the limit of detection (LOD), cultures shifted to net lactate consumption and yielded comparable performances irrespective of the differences in copper levels; when extracellular copper dropped below LOD (∼13 nM), cultures failed to shift to net lactate consumption, and yielded significantly lower product titers. Across the four cell lines, the ability to grow and consume lactate seemed to depend on the presence of a minimum level of copper, beyond which there were no further gains in culture performance. Although this minimum cellular copper requirement could not be directly quantified, we estimated its probable range for the first cell line by applying several assumptions. Even when different copper concentrations did not affect cell culture performance, they affected product quality profiles: higher initial copper concentrations increased the basic variants in the recombinant IgG1 products. Therefore, in optimizing chemically defined media, it is important to select a copper concentration that is adequate and achieves desired product quality attributes. © 2014 American Institute of Chemical Engineers.

The role of choline (Cho) in the diagnostics and differentiation of brain tumours with HMRS technique

International Nuclear Information System (INIS)

Sobiecka, B.; Urbanik, A.

2009-01-01

Background: The aim of the research was a comprehensive analysis of Cho concentration and Cho/Cr, NAA/Cho, NAA/Cho+Cr ratios for the purposes of the diagnostics and differentiation of brain tumours (the type of the pathological lesion in patients with brain tumours) with the use of HMRS technique. Material/Methods: The HMRS examinations were performed with the use of the MRI Signa Excite 1.5 T system, in PRESS technique (TR = 1500 ms, TE = 35 ms) and involved 100 patients with brain tumours (age range: 18 to 81 yrs, mean age 50.61). Spectra were taken from three different locations: tumour centre, the tumour edge and contralateral unchanged cerebral tissue. All patients underwent surgery followed by histopathological analysis, on the basis of which two groups were separated (benign tumours, malignant tumours - 50 cases each). Additionally, 30 healthy volunteers in the age of 20 to 79 years (mean age 40.8) were examined. Results: The comparison of the examined patients with the control group revealed significantly higher Cho concentrations in patients with brain tumours. The analysis of Cho concentration was also performed with consideration of the age factor (under and over 60 years of age). Significantly lower mean Cho concentrations were discovered in a group of patients under 60 years of age. The analysis of Cho concentrations and Cho/Cr ratios reveled statistical significance for two factors: voxel location factor and the type of the pathological lesion. The average of Cho concentration and Cho/Cr ratios were higher in the group of patients with malignant tumours. The highest Cho concentrations and Cho/Cr ratios were observed in the tumour centre. The relative NAA/Cho and NAA/Cho+Cr ratios were statistically significant when taking into consideration the voxel location factor only. The results received from contralateral normal cerebral tissue (the internal model) were compared with control group (the external model). Mean values of Cho concentration were

Identification of a novel temperature sensitive promoter in cho cells

Directory of Open Access Journals (Sweden)

Hesse Friedemann

2011-05-01

Full Text Available Abstract Background The Chinese hamster ovary (CHO expression system is the leading production platform for manufacturing biopharmaceuticals for the treatment of numerous human diseases. Efforts to optimize the production process also include the genetic construct encoding the therapeutic gene. Here we report about the successful identification of an endogenous highly active gene promoter obtained from CHO cells which shows conditionally inducible gene expression at reduced temperature. Results Based on CHO microarray expression data abundantly transcribed genes were selected as potential promoter candidates. The S100a6 (calcyclin and its flanking regions were identified from a genomic CHO-K1 lambda-phage library. Computational analyses showed a predicted TSS, a TATA-box and several TFBSs within the 1.5 kb region upstream the ATG start signal. Various constructs were investigated for promoter activity at 37°C and 33°C in transient luciferase reporter gene assays. Most constructs showed expression levels even higher than the SV40 control and on average a more than two-fold increase at lower temperature. We identified the core promoter sequence (222 bp comprising two SP1 sites and could show a further increase in activity by duplication of this minimal sequence. Conclusions This novel CHO promoter permits conditionally high-level gene expression. Upon a shift to 33°C, a two to three-fold increase of basal productivity (already higher than SV40 promoter is achieved. This property is of particular advantage for a process with reduced expression during initial cell growth followed by the production phase at low temperature with a boost in expression. Additionally, production of toxic proteins becomes feasible, since cell metabolism and gene expression do not directly interfere. The CHO S100a6 promoter can be characterized as cold-shock responsive with the potential for improving process performance of mammalian expression systems.

Hepatitis C Virus NS3/4A Protease Inhibitors Incorporating Flexible P2 Quinoxalines Target Drug Resistant Viral Variants.

Science.gov (United States)

Matthew, Ashley N; Zephyr, Jacqueto; Hill, Caitlin J; Jahangir, Muhammad; Newton, Alicia; Petropoulos, Christos J; Huang, Wei; Kurt-Yilmaz, Nese; Schiffer, Celia A; Ali, Akbar

2017-07-13

A substrate envelope-guided design strategy is reported for improving the resistance profile of HCV NS3/4A protease inhibitors. Analogues of 5172-mcP1P3 were designed by incorporating diverse quinoxalines at the P2 position that predominantly interact with the invariant catalytic triad of the protease. Exploration of structure-activity relationships showed that inhibitors with small hydrophobic substituents at the 3-position of P2 quinoxaline maintain better potency against drug resistant variants, likely due to reduced interactions with residues in the S2 subsite. In contrast, inhibitors with larger groups at this position were highly susceptible to mutations at Arg155, Ala156, and Asp168. Excitingly, several inhibitors exhibited exceptional potency profiles with EC 50 values ≤5 nM against major drug resistant HCV variants. These findings support that inhibitors designed to interact with evolutionarily constrained regions of the protease, while avoiding interactions with residues not essential for substrate recognition, are less likely to be susceptible to drug resistance.

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

Science.gov (United States)

Manning, Alisa K.; Hivert, Marie-France; Scott, Robert A.; Grimsby, Jonna L.; Bouatia-Naji, Nabila; Chen, Han; Rybin, Denis; Liu, Ching-Ti; Bielak, Lawrence F.; Prokopenko, Inga; Amin, Najaf; Barnes, Daniel; Cadby, Gemma; Hottenga, Jouke-Jan; Ingelsson, Erik; Jackson, Anne U.; Johnson, Toby; Kanoni, Stavroula; Ladenvall, Claes; Lagou, Vasiliki; Lahti, Jari; Lecoeur, Cecile; Liu, Yongmei; Martinez-Larrad, Maria Teresa; Montasser, May E.; Navarro, Pau; Perry, John R. B.; Rasmussen-Torvik, Laura J.; Salo, Perttu; Sattar, Naveed; Shungin, Dmitry; Strawbridge, Rona J.; Tanaka, Toshiko; van Duijn, Cornelia M.; An, Ping; de Andrade, Mariza; Andrews, Jeanette S.; Aspelund, Thor; Atalay, Mustafa; Aulchenko, Yurii; Balkau, Beverley; Bandinelli, Stefania; Beckmann, Jacques S.; Beilby, John P.; Bellis, Claire; Bergman, Richard N.; Blangero, John; Boban, Mladen; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L.; Boomsma, Dorret I.; Borecki, Ingrid B.; Böttcher, Yvonne; Bouchard, Claude; Brunner, Eric; Budimir, Danijela; Campbell, Harry; Carlson, Olga; Chines, Peter S.; Clarke, Robert; Collins, Francis S.; Corbatón-Anchuelo, Arturo; Couper, David; de Faire, Ulf; Dedoussis, George V; Deloukas, Panos; Dimitriou, Maria; Egan, Josephine M; Eiriksdottir, Gudny; Erdos, Michael R.; Eriksson, Johan G.; Eury, Elodie; Ferrucci, Luigi; Ford, Ian; Forouhi, Nita G.; Fox, Caroline S; Franzosi, Maria Grazia; Franks, Paul W; Frayling, Timothy M; Froguel, Philippe; Galan, Pilar; de Geus, Eco; Gigante, Bruna; Glazer, Nicole L.; Goel, Anuj; Groop, Leif; Gudnason, Vilmundur; Hallmans, Göran; Hamsten, Anders; Hansson, Ola; Harris, Tamara B.; Hayward, Caroline; Heath, Simon; Hercberg, Serge; Hicks, Andrew A.; Hingorani, Aroon; Hofman, Albert; Hui, Jennie; Hung, Joseph; Jarvelin, Marjo Riitta; Jhun, Min A.; Johnson, Paul C.D.; Jukema, J Wouter; Jula, Antti; Kao, W.H.; Kaprio, Jaakko; Kardia, Sharon L. R.; Keinanen-Kiukaanniemi, Sirkka; Kivimaki, Mika; Kolcic, Ivana; Kovacs, Peter; Kumari, Meena; Kuusisto, Johanna; Kyvik, Kirsten Ohm; Laakso, Markku; Lakka, Timo; Lannfelt, Lars; Lathrop, G Mark; Launer, Lenore J.; Leander, Karin; Li, Guo; Lind, Lars; Lindstrom, Jaana; Lobbens, Stéphane; Loos, Ruth J. F.; Luan, Jian’an; Lyssenko, Valeriya; Mägi, Reedik; Magnusson, Patrik K. E.; Marmot, Michael; Meneton, Pierre; Mohlke, Karen L.; Mooser, Vincent; Morken, Mario A.; Miljkovic, Iva; Narisu, Narisu; O’Connell, Jeff; Ong, Ken K.; Oostra, Ben A.; Palmer, Lyle J.; Palotie, Aarno; Pankow, James S.; Peden, John F.; Pedersen, Nancy L.; Pehlic, Marina; Peltonen, Leena; Penninx, Brenda; Pericic, Marijana; Perola, Markus; Perusse, Louis; Peyser, Patricia A; Polasek, Ozren; Pramstaller, Peter P.; Province, Michael A.; Räikkönen, Katri; Rauramaa, Rainer; Rehnberg, Emil; Rice, Ken; Rotter, Jerome I.; Rudan, Igor; Ruokonen, Aimo; Saaristo, Timo; Sabater-Lleal, Maria; Salomaa, Veikko; Savage, David B.; Saxena, Richa; Schwarz, Peter; Seedorf, Udo; Sennblad, Bengt; Serrano-Rios, Manuel; Shuldiner, Alan R.; Sijbrands, Eric J.G.; Siscovick, David S.; Smit, Johannes H.; Small, Kerrin S.; Smith, Nicholas L.; Smith, Albert Vernon; Stančáková, Alena; Stirrups, Kathleen; Stumvoll, Michael; Sun, Yan V.; Swift, Amy J.; Tönjes, Anke; Tuomilehto, Jaakko; Trompet, Stella; Uitterlinden, Andre G.; Uusitupa, Matti; Vikström, Max; Vitart, Veronique; Vohl, Marie-Claude; Voight, Benjamin F.; Vollenweider, Peter; Waeber, Gerard; Waterworth, Dawn M; Watkins, Hugh; Wheeler, Eleanor; Widen, Elisabeth; Wild, Sarah H.; Willems, Sara M.; Willemsen, Gonneke; Wilson, James F.; Witteman, Jacqueline C.M.; Wright, Alan F.; Yaghootkar, Hanieh; Zelenika, Diana; Zemunik, Tatijana; Zgaga, Lina; Wareham, Nicholas J.; McCarthy, Mark I.; Barroso, Ines; Watanabe, Richard M.; Florez, Jose C.; Dupuis, Josée; Meigs, James B.; Langenberg, Claudia

2013-01-01

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction, but contributed little to our understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways may be uncovered by accounting for differences in body mass index (BMI) and potential interaction between BMI and genetic variants. We applied a novel joint meta-analytical approach to test associations with fasting insulin (FI) and glucose (FG) on a genome-wide scale. We present six previously unknown FI loci at P<5×10−8 in combined discovery and follow-up analyses of 52 studies comprising up to 96,496non-diabetic individuals. Risk variants were associated with higher triglyceride and lower HDL cholesterol levels, suggestive of a role for these FI loci in insulin resistance pathways. The localization of these additional loci will aid further characterization of the role of insulin resistance in T2D pathophysiology. PMID:22581228

Synthesis of cadmium tungstate films via sol-gel processing

Energy Technology Data Exchange (ETDEWEB)

Lennstrom, Kirk; Limmer, Steven J.; Cao Guozhong

2003-06-23

Cadmium tungstate is a scintillator material with excellent intrinsic photoluminescent properties. It is highly resistant to gamma radiation, has an almost non-existent afterglow and is highly efficient. Cadmium tungstate is also non-hydroscopic, unlike the more prevalent thallium-doped alkali halide scintillators. In order to create thin films of cadmium tungstate with precise stoichiometric control, a sol-gel processing technique has been applied to produce this material for the first time. In addition to lower processing temperatures, sol-gel-derived cadmium tungstate is cheaper and easier than other technologies, particularly for thin films. Furthermore, it has the potential to produce nanostructured materials with good optical quality. X-Ray diffraction results of sol-gel-derived materials fired at various temperatures imply crystallization of cadmium tungstate without the intermediate formation of either tungsten oxide or cadmium oxide. Scanning electron microscopy analysis shows the formation of nano-sized particles prior to heat treatment, which form meso-sized particles after the heat treatment. Photoluminesce analysis indicates emission of derived films at 480 nm, which agrees with other published data. Finally, the efficiency of derived films was approximately 6%{+-}1.8%.

Low fraction of the 222K PrP variant in the protease-resistant moiety of PrPres in heterozygous scrapie positive goats.

Science.gov (United States)

Mazza, Maria; Guglielmetti, Chiara; Ingravalle, Francesco; Brusadore, Sonia; Langeveld, Jan P M; Ekateriniadou, Loukia V; Andréoletti, Olivier; Casalone, Cristina; Acutis, Pier Luigi

2017-07-01

The presence of lysine (K) at codon 222 has been associated with resistance to classical scrapie in goats, but few scrapie cases have been identified in 222Q/K animals. To investigate the contribution of the 222K variant to PrPres formation in natural and experimental Q/K scrapie cases, we applied an immunoblotting method based on the use of two different monoclonal antibodies, F99/97.6.1 and SAF84, chosen for their different affinities to 222K and 222Q PrP variants. Our finding that PrPres seems to be formed nearly totally by the 222Q variant provides evidence that the 222K PrP variant confers resistance to conversion to PrPres formation and reinforces the view that this mutation has a protective role against classical scrapie in goats.

Network reconstruction of the mouse secretory pathway applied on CHO cell transcriptome data

DEFF Research Database (Denmark)

Lund, Anne Mathilde; Kaas, Christian Schrøder; Brandl, Julian

2017-01-01

, counting 801 different components in mouse. By employing our mouse RECON to the CHO-K1 genome in a comparative genomic approach, we could reconstruct the protein secretory pathway of CHO cells counting 764 CHO components. This RECON furthermore facilitated the development of three alternative methods...... to study protein secretion through graphical visualizations of omics data. We have demonstrated the use of these methods to identify potential new and known targets for engineering improved growth and IgG production, as well as the general observation that CHO cells seem to have less strict transcriptional...... regulation of protein secretion than healthy mouse cells.  Conclusions: The RECON of the secretory pathway represents a strong tool for interpretation of data related to protein secretion as illustrated with transcriptomic data of Chinese Hamster Ovary (CHO) cells, the main platform for mammalian protein...

The apoptosis of CHO cells induced by X-rays

International Nuclear Information System (INIS)

Lu Zhaohong; Zhao Jingyong; Zhu Mingqing; Shi Xijin; Wang Chunlei

2004-01-01

The work is to study the mechanism of toxic effects on reproductive system and apoptosis of Chinese hamster ovary (CHO) cells induced by X-rays. CHO cell was exposed to X-rays 2 to 20 Gy. Apoptosis and morphological changes of the cells were observed by fluorescent microscopy and flow cytometry analyzer with double staining with Annexin V/PI. The apoptosis could be observed at 24, 48 and 72h after the exposure, but it was more obvious 48 and 72 h after the exposure. Rate of the apoptosis increased along with radiation dose were elevated. Some morphological changes, such as irregular agglomerate of chromatins, pycnosis and periphery distribution of nuclei, crescent-moon-like cells, small apoptosis body, were observed. Radiation results DNA damage in the CHO cells, and the damage cannot be repaired, hence the induced cell apoptosis. (authors)

Molecular mechanisms of plasmid-determined mercury and cadmium resistances in bacteria

International Nuclear Information System (INIS)

Nucifora, G.

1989-01-01

The structural basis for induction of the broad spectrum mercurial resistance operon of pDU1358 with inorganic mercury and with phenylmercury acetate was addressed by DNA sequencing analysis (that showed that a major difference occurred in the 3' 29 base pairs of the ital merR gene compared to the merR genes of Tn501 and R100) and by lac-fusion transcription experiments regulated by merR in trans. The lac-fusion results were compared with those from a narrow spectrum operon, and the pDU1358 merR deleted at the 3' end. A hybrid mer operon containing the merR gene from pDU1358 and lacking the merB gene was inducible by both phenylmercury and inorganic Hg 2+ , showing that organomercurial lyase is not needed for induction by organomercurials. A mutant form of pDU1358 merR missing the C-terminal 17 amino acids responded to inorganic Hg 2+ but not to phenylmercury, indicating that the C-terminal region of the MerR protein of the pDU1358 mer operon is required for the recognition of phenylmercury acetate. The down regulation of the mer operon by the merD gene was also measured in trans with complementing mer operons of pDU1358 or R100 or merD - mutants. In the presence of the merD gene, beta-galactosidase activity was lowered by 2 to 4 fold. The merD gene gene product was visualized by autoradiography. The Cd 2+ resistance determinant cadA of S. aureus was investigated. The nucleotide sequence of the DNA fragment containing the cadA determinant revealed two open reading frames the larger one of which is essential for expression of cadmium resistance

Low-abundance HIV drug-resistant viral variants in treatment-experienced persons correlate with historical antiretroviral use.

Science.gov (United States)

Le, Thuy; Chiarella, Jennifer; Simen, Birgitte B; Hanczaruk, Bozena; Egholm, Michael; Landry, Marie L; Dieckhaus, Kevin; Rosen, Marc I; Kozal, Michael J

2009-06-29

It is largely unknown how frequently low-abundance HIV drug-resistant variants at levels under limit of detection of conventional genotyping (<20% of quasi-species) are present in antiretroviral-experienced persons experiencing virologic failure. Further, the clinical implications of low-abundance drug-resistant variants at time of virologic failure are unknown. Plasma samples from 22 antiretroviral-experienced subjects collected at time of virologic failure (viral load 1380 to 304,000 copies/mL) were obtained from a specimen bank (from 2004-2007). The prevalence and profile of drug-resistant mutations were determined using Sanger sequencing and ultra-deep pyrosequencing. Genotypes were interpreted using Stanford HIV database algorithm. Antiretroviral treatment histories were obtained by chart review and correlated with drug-resistant mutations. Low-abundance drug-resistant mutations were detected in all 22 subjects by deep sequencing and only in 3 subjects by Sanger sequencing. In total they accounted for 90 of 247 mutations (36%) detected by deep sequencing; the majority of these (95%) were not detected by standard genotyping. A mean of 4 additional mutations per subject were detected by deep sequencing (p<0.0001, 95%CI: 2.85-5.53). The additional low-abundance drug-resistant mutations increased a subject's genotypic resistance to one or more antiretrovirals in 17 of 22 subjects (77%). When correlated with subjects' antiretroviral treatment histories, the additional low-abundance drug-resistant mutations correlated with the failing antiretroviral drugs in 21% subjects and correlated with historical antiretroviral use in 79% subjects (OR, 13.73; 95% CI, 2.5-74.3, p = 0.0016). Low-abundance HIV drug-resistant mutations in antiretroviral-experienced subjects at time of virologic failure can increase a subject's overall burden of resistance, yet commonly go unrecognized by conventional genotyping. The majority of unrecognized resistant mutations correlate with

Low-abundance HIV drug-resistant viral variants in treatment-experienced persons correlate with historical antiretroviral use.

Directory of Open Access Journals (Sweden)

Thuy Le

Full Text Available BACKGROUND: It is largely unknown how frequently low-abundance HIV drug-resistant variants at levels under limit of detection of conventional genotyping (<20% of quasi-species are present in antiretroviral-experienced persons experiencing virologic failure. Further, the clinical implications of low-abundance drug-resistant variants at time of virologic failure are unknown. METHODOLOGY/PRINCIPAL FINDINGS: Plasma samples from 22 antiretroviral-experienced subjects collected at time of virologic failure (viral load 1380 to 304,000 copies/mL were obtained from a specimen bank (from 2004-2007. The prevalence and profile of drug-resistant mutations were determined using Sanger sequencing and ultra-deep pyrosequencing. Genotypes were interpreted using Stanford HIV database algorithm. Antiretroviral treatment histories were obtained by chart review and correlated with drug-resistant mutations. Low-abundance drug-resistant mutations were detected in all 22 subjects by deep sequencing and only in 3 subjects by Sanger sequencing. In total they accounted for 90 of 247 mutations (36% detected by deep sequencing; the majority of these (95% were not detected by standard genotyping. A mean of 4 additional mutations per subject were detected by deep sequencing (p<0.0001, 95%CI: 2.85-5.53. The additional low-abundance drug-resistant mutations increased a subject's genotypic resistance to one or more antiretrovirals in 17 of 22 subjects (77%. When correlated with subjects' antiretroviral treatment histories, the additional low-abundance drug-resistant mutations correlated with the failing antiretroviral drugs in 21% subjects and correlated with historical antiretroviral use in 79% subjects (OR, 13.73; 95% CI, 2.5-74.3, p = 0.0016. CONCLUSIONS/SIGNIFICANCE: Low-abundance HIV drug-resistant mutations in antiretroviral-experienced subjects at time of virologic failure can increase a subject's overall burden of resistance, yet commonly go unrecognized by conventional

Androgen Receptor Variant AR-V9 Is Coexpressed with AR-V7 in Prostate Cancer Metastases and Predicts Abiraterone Resistance.

Science.gov (United States)

Kohli, Manish; Ho, Yeung; Hillman, David W; Van Etten, Jamie L; Henzler, Christine; Yang, Rendong; Sperger, Jamie M; Li, Yingming; Tseng, Elizabeth; Hon, Ting; Clark, Tyson; Tan, Winston; Carlson, Rachel E; Wang, Liguo; Sicotte, Hugues; Thai, Ho; Jimenez, Rafael; Huang, Haojie; Vedell, Peter T; Eckloff, Bruce W; Quevedo, Jorge F; Pitot, Henry C; Costello, Brian A; Jen, Jin; Wieben, Eric D; Silverstein, Kevin A T; Lang, Joshua M; Wang, Liewei; Dehm, Scott M

2017-08-15

Purpose: Androgen receptor (AR) variant AR-V7 is a ligand-independent transcription factor that promotes prostate cancer resistance to AR-targeted therapies. Accordingly, efforts are under way to develop strategies for monitoring and inhibiting AR-V7 in castration-resistant prostate cancer (CRPC). The purpose of this study was to understand whether other AR variants may be coexpressed with AR-V7 and promote resistance to AR-targeted therapies. Experimental Design: We utilized complementary short- and long-read sequencing of intact AR mRNA isoforms to characterize AR expression in CRPC models. Coexpression of AR-V7 and AR-V9 mRNA in CRPC metastases and circulating tumor cells was assessed by RNA-seq and RT-PCR, respectively. Expression of AR-V9 protein in CRPC models was evaluated with polyclonal antisera. Multivariate analysis was performed to test whether AR variant mRNA expression in metastatic tissues was associated with a 12-week progression-free survival endpoint in a prospective clinical trial of 78 CRPC-stage patients initiating therapy with the androgen synthesis inhibitor, abiraterone acetate. Results: AR-V9 was frequently coexpressed with AR-V7. Both AR variant species were found to share a common 3' terminal cryptic exon, which rendered AR-V9 susceptible to experimental manipulations that were previously thought to target AR-V7 uniquely. AR-V9 promoted ligand-independent growth of prostate cancer cells. High AR-V9 mRNA expression in CRPC metastases was predictive of primary resistance to abiraterone acetate (HR = 4.0; 95% confidence interval, 1.31-12.2; P = 0.02). Conclusions: AR-V9 may be an important component of therapeutic resistance in CRPC. Clin Cancer Res; 23(16); 4704-15. ©2017 AACR . ©2017 American Association for Cancer Research.

MRP proteins as potential mediators of heavy metal resistance in zebrafish cells.

Science.gov (United States)

Long, Yong; Li, Qing; Wang, Youhui; Cui, Zongbin

2011-04-01

Acquired resistance of mammalian cells to heavy metals is closely relevant to enhanced expression of several multidrug resistance-associated proteins (MRP), but it remains unclear whether MRP proteins confer resistance to heavy metals in zebrafish. In this study, we obtained zebrafish (Danio rerio) fibroblast-like ZF4 cells with resistance to toxic heavy metals after chronic cadmium exposure and selection for 6months. These cadmium-resistant cells (ZF4-Cd) were maintained in 5μM cadmium and displayed cross-resistance to cadmium, mercury, arsenite and arsenate. ZF4-Cd cells remained the resistance to heavy metals after protracted culture in cadmium-free medium. In comparison with ZF4-WT cells, ZF4-Cd cells exhibited accelerated rate of cadmium excretion, enhanced activity of MRP-like transport, elevated expression of abcc2, abcc4 and mt2 genes, and increased content of cellular GSH. Inhibition of MRP-like transport activity, GSH biosynthesis and GST activity significantly attenuated the resistance of ZF4-Cd cells to heavy metals. The results indicate that some of MRP transporters are involved in the efflux of heavy metals conjugated with cellular GSH and thus play crucial roles in heavy metal detoxification of zebrafish cells. Copyright © 2010 Elsevier Inc. All rights reserved.

A novel BHLHE41 variant is associated with short sleep and resistance to sleep deprivation in humans.

Science.gov (United States)

Pellegrino, Renata; Kavakli, Ibrahim Halil; Goel, Namni; Cardinale, Christopher J; Dinges, David F; Kuna, Samuel T; Maislin, Greg; Van Dongen, Hans P A; Tufik, Sergio; Hogenesch, John B; Hakonarson, Hakon; Pack, Allan I

2014-08-01

Earlier work described a mutation in DEC2 also known as BHLHE41 (basic helix-loophelix family member e41) as causal in a family of short sleepers, who needed just 6 h sleep per night. We evaluated whether there were other variants of this gene in two well-phenotyped cohorts. Sequencing of the BHLHE41 gene, electroencephalographic data, and delta power analysis and functional studies using cell-based luciferase. We identified new variants of the BHLHE41 gene in two cohorts who had either acute sleep deprivation (n = 200) or chronic partial sleep deprivation (n = 217). One variant, Y362H, at another location in the same exon occurred in one twin in a dizygotic twin pair and was associated with reduced sleep duration, less recovery sleep following sleep deprivation, and fewer performance lapses during sleep deprivation than the homozygous twin. Both twins had almost identical amounts of non rapid eye movement (NREM) sleep. This variant reduced the ability of BHLHE41 to suppress CLOCK/BMAL1 and NPAS2/BMAL1 transactivation in vitro. Another variant in the same exome had no effect on sleep or response to sleep deprivation and no effect on CLOCK/BMAL1 transactivation. Random mutagenesis identified a number of other variants of BHLHE41 that affect its function. There are a number of mutations of BHLHE41. Mutations reduce total sleep while maintaining NREM sleep and provide resistance to the effects of sleep loss. Mutations that affect sleep also modify the normal inhibition of BHLHE41 of CLOCK/BMAL1 transactivation. Thus, clock mechanisms are likely involved in setting sleep length and the magnitude of sleep homeostasis. Pellegrino R, Kavakli IH, Goel N, Cardinale CJ, Dinges DF, Kuna ST, Maislin G, Van Dongen HP, Tufik S, Hogenesch JB, Hakonarson H, Pack AI. A novel BHLHE41 variant is associated with short sleep and resistance to sleep deprivation in humans. SLEEP 2014;37(8):1327-1336.

In vitro selection of rape variants resistant to oxalic acid using haploid stem apexes

International Nuclear Information System (INIS)

Wang Yifei; Huang Jianhua; Lu Ruiju; Sun Yuefang; Zhou Runmei; Zhou Zhijiang; Xie Zhujie; Liu Chenghong

2002-01-01

Mutagenic treatment was made of the haploid stem apexes rape strain '9841' and '9885' with Pingyangmycin. As a result of positive selection with oxalic acid providing selection pressure, variants with significantly higher tolerance to oxalic acid than the original ones were obtained. 3 germplasm with significantly higher resistance to Sclerotinia sclerotiorum than cultivar Hu You 12 were selected from field test

Acromegaly Is More Severe in Patients With AHR or AIP Gene Variants Living in Highly Polluted Areas.

Science.gov (United States)

Cannavo, S; Ragonese, M; Puglisi, S; Romeo, P D; Torre, M L; Alibrandi, A; Scaroni, C; Occhi, G; Ceccato, F; Regazzo, D; De Menis, E; Sartorato, P; Arnaldi, G; Trementino, L; Trimarchi, F; Ferrau, F

2016-04-01

An increased prevalence of acromegaly was found some years ago in a highly polluted area in North-Eastern Sicily, where high concentration of nonmethane hydrocarbons, volatile organic compounds, and cadmium was found. Aryl hydrocarbon receptor (AHR) pathway has a key role in detoxification of these compounds and in tumorigenesis. We correlated the occurrence of AHR and/or AHR-interacting protein (AIP) gene variants with acromegaly severity according to pollution exposition. This was an observational, perspective study conducted over 7 years in four Italian referral centers for pituitary diseases in which 210 patients with acromegaly were enrolled between 2008 and 2015. Genetic screening of patients for AHR and AIP variants. Clinical, biochemical, and radiological data of patients with and without AIP and/or AHR gene variants, living in polluted (high-risk for health, [HR]) or nonpolluted (NP) areas of five Italian regions were evaluated and compared. Among the 23 patients from HR areas, nine showed AHR or AIP variants. Mean IGF-I levels and pituitary tumor diameter were significantly higher in these nine patients (HR/VAR+) than in the other 14 (HR/VAR−) and in the 187 from NP areas (44 NP/VAR+). Somatostatin analogs significantly decreased mean GH and IGF-I levels in patients from NP areas and in HR/VAR− (GH P acromegaly, increased pituitary tumor size, and somatostatin analog resistance in patients living in HR areas.

RNA-Seq Highlights High Clonal Variation in Monoclonal Antibody Producing CHO Cells

DEFF Research Database (Denmark)

Orellana, Camila A.; Marcellin, Esteban; Palfreyman, Robin W.

2018-01-01

The development of next-generation sequencing technologies has opened new opportunities to better characterize complex eukaryotic cells. Chinese hamster ovary (CHO) cells play a primary role in therapeutic protein production, with currently five of the top ten blockbuster drugs produced in CHO......-regulation of genes encoding secreted glycoproteins is found to be the most significant change. The large number of significant differences even between subclones challenges the notion of identifying and manipulating a few key genes to generate high production CHO cell lines....

CHOmine: an integrated data warehouse for CHO systems biology and modeling.

Science.gov (United States)

Gerstl, Matthias P; Hanscho, Michael; Ruckerbauer, David E; Zanghellini, Jürgen; Borth, Nicole

2017-01-01

The last decade has seen a surge in published genome-scale information for Chinese hamster ovary (CHO) cells, which are the main production vehicles for therapeutic proteins. While a single access point is available at www.CHOgenome.org, the primary data is distributed over several databases at different institutions. Currently research is frequently hampered by a plethora of gene names and IDs that vary between published draft genomes and databases making systems biology analyses cumbersome and elaborate. Here we present CHOmine, an integrative data warehouse connecting data from various databases and links to other ones. Furthermore, we introduce CHOmodel, a web based resource that provides access to recently published CHO cell line specific metabolic reconstructions. Both resources allow to query CHO relevant data, find interconnections between different types of data and thus provides a simple, standardized entry point to the world of CHO systems biology. http://www.chogenome.org. © The Author(s) 2017. Published by Oxford University Press.

Widespread extrahippocampal NAA/(Cr+Cho) abnormalities in TLE with and without mesial temporal sclerosis.

Science.gov (United States)

Mueller, Susanne G; Ebel, Andreas; Barakos, Jerome; Scanlon, Cathy; Cheong, Ian; Finlay, Daniel; Garcia, Paul; Weiner, Michael W; Laxer, Kenneth D

2011-04-01

MR spectroscopy has demonstrated extrahippocampal NAA/(Cr+Cho) reductions in medial temporal lobe epilepsy with (TLE-MTS) and without (TLE-no) mesial temporal sclerosis. Because of the limited brain coverage of those previous studies, it was, however, not possible to assess differences in the distribution and extent of these abnormalities between TLE-MTS and TLE-no. This study used a 3D whole brain echoplanar spectroscopic imaging (EPSI) sequence to address the following questions: (1) Do TLE-MTS and TLE-no differ regarding severity and distribution of extrahippocampal NAA/(Cr+Cho) reductions? (2) Do extrahippocampal NAA/(Cr+Cho) reductions provide additional information for focus lateralization? Forty-three subjects (12 TLE-MTS, 13 TLE-no, 18 controls) were studied with 3D EPSI. Statistical parametric mapping (SPM2) was used to identify regions of significantly decreased NAA/(Cr+Cho) in TLE groups and in individual patients. TLE-MTS and TLE-no had widespread extrahippocampal NAA/(Cr+Cho) reductions. NAA/(Cr+Cho) reductions had a bilateral fronto-temporal distribution in TLE-MTS and a more diffuse, less well defined distribution in TLE-no. Extrahippocampal NAA/(Cr+Cho) decreases in the single subject analysis showed a large inter-individual variability and did not provide additional focus lateralizing information. Extrahippocampal NAA/(Cr+Cho) reductions in TLE-MTS and TLE-no are neither focal nor homogeneous. This reduces their value for focus lateralization and suggests a heterogeneous etiology of extrahippocampal spectroscopic metabolic abnormalities in TLE.

The GalNAc-type O-Glycoproteome of CHO Cells Characterized by the SimpleCell Strategy

DEFF Research Database (Denmark)

Zhang, Yang; Halim, Adnan; Narimatsu, Yoshiki

2014-01-01

The Chinese hamster ovary cell (CHO) is the major host cell factory for recombinant production of biological therapeutics primarily because of its “human-like” glycosylation features. CHO is used for production of several O-glycoprotein therapeutics including erythropoietin, coagulation factors......, and chimeric receptor IgG1-Fc-fusion proteins, however, some O-glycoproteins are not produced efficiently in CHO. We have previously shown that the capacity for O-glycosylation of proteins can be one limiting parameter for production of active proteins in CHO. Although the capacity of CHO for biosynthesis...... of glycan structures (glycostructures) on glycoproteins are well established, our knowledge of the capacity of CHO cells for attaching GalNAc-type O-glycans to proteins (glycosites) is minimal. This type of O-glycosylation is one of the most abundant forms of glycosylation, and it is differentially...

HIV-1 Variants and Drug Resistance in Pregnant Women from Bata (Equatorial Guinea): 2012-2013.

Science.gov (United States)

Alvarez, Patricia; Fernández McPhee, Carolina; Prieto, Luis; Martín, Leticia; Obiang, Jacinta; Avedillo, Pedro; Vargas, Antonio; Rojo, Pablo; Benito, Agustín; Ramos, José Tomás; Holguín, África

2016-01-01

This is the first study describing drug resistance mutations (DRM) and HIV-1 variants among infected pregnant women in Equatorial Guinea (GQ), a country with high (6.2%) and increasing HIV prevalence. Dried blood spots (DBS) were collected from November 2012 to December 2013 from 69 HIV-1 infected women participating in a prevention of mother-to-child transmission program in the Hospital Regional of Bata and Primary Health Care Centre María Rafols, Bata, GQ. The transmitted (TDR) or acquired (ADR) antiretroviral drug resistance mutations at partial pol sequence among naive or antiretroviral therapy (ART)-exposed women were defined following WHO or IAS USA 2015 lists, respectively. HIV-1 variants were identified by phylogenetic analyses. A total of 38 of 69 HIV-1 specimens were successfully amplified and sequenced. Thirty (79%) belonged to ART-experienced women: 15 exposed to nucleoside reverse transcriptase inhibitors (NRTI) monotherapy, and 15 to combined ART (cART) as first regimen including two NRTI and one non-NRTI (NNRTI) or one protease inhibitor (PI). The TDR rate was only found for PI (3.4%). The ADR rate was 37.5% for NNRTI, 8.7% for NRTI and absent for PI or NRTI+NNRTI. HIV-1 group M non-B variants caused most (97.4%) infections, mainly (78.9%) recombinants: CRF02_AG (55.2%), CRF22_A101 (10.5%), subtype C (10.5%), unique recombinants (5.3%), and A3, D, F2, G, CRF06_cpx and CRF11_cpx (2.6% each). The high rate of ADR to retrotranscriptase inhibitors (mainly to NNRTIs) observed among pretreated pregnant women reinforces the importance of systematic DRM monitoring in GQ to reduce HIV-1 resistance transmission and to optimize first and second-line ART regimens when DRM are present.

Contribution of HIV minority variants to drug resistance in an integrase strand transfer inhibitor-based therapy

Czech Academy of Sciences Publication Activity Database

Weber, Jan; Gibson, R. M.; Meyer, A. M.; Winner, D.; Robertson, D. L.; Miller, M. D.; Quinones-Mateu, M. E.

2013-01-01

Roč. 18, Suppl. 1 (2013), A66-A66 ISSN 1359-6535. [International Workshop on HIV & Hepatitis Virus Drug Resistance Curative Strategies. 04.06.2013-08.06.2013, Toronto] Institutional support: RVO:61388963 Keywords : HIV minority variants * integrase inhibitor * replicative fitness Subject RIV: CE - Biochemistry

Bacterial bioremediation of aquatic cadmium 11 of area of Pakistan

International Nuclear Information System (INIS)

Mahmood, T.; Malik, S. A.; Javed, M.; Qamar, I.

2005-01-01

Cadmium Cd/sup +2/ pollution arises mainly from contamination of minerals used in agriculture and from industrial process. The usual situation is of large volume of soil and H/sub 2/O that are contaminated with low but significant concentration of Cd/sup +2/. Cadmium is one of the most dangerous heavy metal both to human health and aquatic ecosystem. Microorganisms have developed different strategies to regulate uptake and to detoxify heavy metals viz; by different mechanisms i.e. by adsorption to cell surface, by intercellular accumulation, precipitation, biosynthesis of metallothioneins to volatile compounds. Microcosm experiments in chemostat incubated at 20 deg. C showed that Cadmium Contamination does not greatly affect bacterial communities in cultures contaminated with up to 1mg CdI/sup -1/. acterial productivity remains unchanged and Cadmium- resistant strains arise quickly and in great number. The cadmium accumulation by bacteria depend on the bacterial productivity. The free bacteria can accumulate up to 1200 ppm Cadmium Where as the adhering bacteria concentrate up to 6100 ppm. At a steady state, 11-29% Cadmium is removed from the water phase of cultures. This paper includes Cd (II) removal by Bacteria from waste water of Wah Cantonment Pakistan. (author)

Development of autochthonous microbial consortia for enhanced phytoremediation of salt-marsh sediments contaminated with cadmium.

Science.gov (United States)

Teixeira, Catarina; Almeida, C Marisa R; Nunes da Silva, Marta; Bordalo, Adriano A; Mucha, Ana P

2014-09-15

Microbial assisted phytoremediation is a promising, though yet poorly explored, new remediation technique. The aim of this study was to develop autochthonous microbial consortia resistant to cadmium that could enhance phytoremediation of salt-marsh sediments contaminated with this metal. The microbial consortia were selectively enriched from rhizosediments colonized by Juncus maritimus and Phragmites australis. The obtained consortia presented similar microbial abundance but a fairly different community structure, showing that the microbial community was a function of the sediment from which the consortia were enriched. The effect of the bioaugmentation with the developed consortia on cadmium uptake, and the microbial community structure associated to the different sediments were assessed using a microcosm experiment. Our results showed that the addition of the cadmium resistant microbial consortia increased J. maritimus metal phytostabilization capacity. On the other hand, in P. australis, microbial consortia amendment promoted metal phytoextraction. The addition of the consortia did not alter the bacterial structure present in the sediments at the end of the experiments. This study provides new evidences that the development of autochthonous microbial consortia for enhanced phytoremediation of salt-marsh sediments contaminated with cadmium might be a simple, efficient, and environmental friendly remediation procedure. Development of autochthonous microbial consortia resistant to cadmium that enhanced phytoremediation by salt-marsh plants, without a long term effect on sediment bacterial diversity. Copyright © 2014 Elsevier B.V. All rights reserved.

RNA-seq based expression analysis of the CHO cell protein secretion pathway

DEFF Research Database (Denmark)

Lund, Anne Mathilde; Kaas, Christian Schrøder; Kildegaard, Helene Faustrup

The Chinese hamster ovary (CHO) cell-line is the predominant mammalian industrial cell line being used to produce recombinant therapeutic proteins. Although CHO cells have been used for more than 25 years, the genome sequence was first published in 2011. So far there have been limited studies...... of the cell biology of the CHO cell and the potential of cell line engineering. To elucidate the poorly understood cellular processes that control and limit recombinant protein production and secretion, a system-wide study was initiated to identify possible engineering targets relevant for therapeutic protein...

Effect of Ampicillin, Streptomycin, Penicillin and Tetracycline on Metal Resistant and Non-Resistant Staphylococcus aureus

Directory of Open Access Journals (Sweden)

Dagmar Chudobova

2014-03-01

Full Text Available There is an arising and concerning issue in the field of bacterial resistance, which is confirmed by the number of deaths associated with drug-resistant bacterial infections. The aim of this study was to compare the effects of antibiotics on Staphylococcus aureus non-resistant strain and strains resistant to cadmium or lead ions. Metal resistant strains were created by the gradual addition of 2 mM solution of metal ions (cadmium or lead to the S. aureus culture. An increasing antimicrobial effect of ampicillin, streptomycin, penicillin and tetracycline (0, 10, 25, 50, 75, 150, 225 and 300 µM on the resistant strains was observed using a method of growth curves. A significant growth inhibition (compared to control of cadmium resistant cells was observed in the presence of all the four different antibiotics. On the other hand, the addition of streptomycin and ampicillin did not inhibit the growth of lead resistant strain. Other antibiotics were still toxic to the bacterial cells. Significant differences in the morphology of cell walls were indicated by changes in the cell shape. Our data show that the presence of metal ions in the urban environment may contribute to the development of bacterial strain resistance to other substances including antibiotics, which would have an impact on public health.

Effect of Ampicillin, Streptomycin, Penicillin and Tetracycline on Metal Resistant and Non-Resistant Staphylococcus aureus

Science.gov (United States)

Chudobova, Dagmar; Dostalova, Simona; Blazkova, Iva; Michalek, Petr; Ruttkay-Nedecky, Branislav; Sklenar, Matej; Nejdl, Lukas; Kudr, Jiri; Gumulec, Jaromir; Tmejova, Katerina; Konecna, Marie; Vaculovicova, Marketa; Hynek, David; Masarik, Michal; Kynicky, Jindrich; Kizek, Rene; Adam, Vojtech

2014-01-01

There is an arising and concerning issue in the field of bacterial resistance, which is confirmed by the number of deaths associated with drug-resistant bacterial infections. The aim of this study was to compare the effects of antibiotics on Staphylococcus aureus non-resistant strain and strains resistant to cadmium or lead ions. Metal resistant strains were created by the gradual addition of 2 mM solution of metal ions (cadmium or lead) to the S. aureus culture. An increasing antimicrobial effect of ampicillin, streptomycin, penicillin and tetracycline (0, 10, 25, 50, 75, 150, 225 and 300 µM) on the resistant strains was observed using a method of growth curves. A significant growth inhibition (compared to control) of cadmium resistant cells was observed in the presence of all the four different antibiotics. On the other hand, the addition of streptomycin and ampicillin did not inhibit the growth of lead resistant strain. Other antibiotics were still toxic to the bacterial cells. Significant differences in the morphology of cell walls were indicated by changes in the cell shape. Our data show that the presence of metal ions in the urban environment may contribute to the development of bacterial strain resistance to other substances including antibiotics, which would have an impact on public health. PMID:24651395

Effects of preoperative feeding with a whey protein plus carbohydrate drink on the acute phase response and insulin resistance. A randomized trial

Directory of Open Access Journals (Sweden)

Dock-Nascimento Diana B

2011-06-01

Full Text Available Abstract Background Prolonged preoperative fasting increases insulin resistance and current evidence recommends carbohydrate (CHO drinks 2 hours before surgery. Our hypothesis is that the addition of whey protein to a CHO-based drink not only reduces the inflammatory response but also diminish insulin resistance. Methods Seventeen patients scheduled to cholecystectomy or inguinal herniorraphy were randomized and given 474 ml and 237 ml of water (CO group or a drink containing CHO and milk whey protein (CHO-P group respectively, 6 and 3 hours before operation. Blood samples were collected before surgery and 24 hours afterwards for biochemical assays. The endpoints of the study were the insulin resistance (IR, the prognostic inflammatory and nutritional index (PINI and the C-reactive protein (CRP/albumin ratio. A 5% level for significance was established. Results There were no anesthetic or postoperative complications. The post-operative IR was lower in the CHO-P group when compared with the CO group (2.75 ± 0.72 vs 5.74 ± 1.16; p = 0.03. There was no difference between the two groups in relation to the PINI. The CHO-P group showed a decrease in the both CRP elevation and CRP/albumin ratio (p Conclusions Shortening the pre-operative fasting using CHO and whey protein is safe and reduces insulin resistance and postoperative acute phase response in elective moderate operations. Trial registration ClinicalTrail.gov NCT01354249

CRISPR/Cas9-mediated genome engineering of CHO cell factories: application and perspectives

DEFF Research Database (Denmark)

Lee, Jae Seong; Grav, Lise Marie; Lewis, Nathan E.

2015-01-01

repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system enables rapid,easy and efficient engineering of mammalian genomes. It has a wide range of applications frommodification of individual genes to genome-wide screening or regulation of genes. Facile genomeediting using CRISPR/Cas9 empowers...... researchers in the CHO community to elucidate the mechanisticbasis behind high level production of proteins and product quality attributes of interest. Inthis review, we describe the basis of CRISPR/Cas9-mediated genome editing and its applicationfor development of next generation CHO cell factories while...... highlighting both future perspectivesand challenges. As one of the main drivers for the CHO systems biology era, genome engineeringwith CRISPR/Cas9 will pave the way for rational design of CHO cell factories....

A proteomic study of cMyc improvement of CHO culture

Directory of Open Access Journals (Sweden)

Dunn Michael J

2010-03-01

Full Text Available Abstract Background The biopharmaceutical industry requires cell lines to have an optimal proliferation rate and a high integral viable cell number resulting in a maximum volumetric recombinant protein product titre. Nutrient feeding has been shown to boost cell number and productivity in fed-batch culture, but cell line engineering is another route one may take to increase these parameters in the bioreactor. The use of CHO-K1 cells with a c-myc plasmid allowing for over-expressing c-Myc (designated cMycCHO gives a higher integral viable cell number. In this study the differential protein expression in cMycCHO is investigated using two-dimensional gel electrophoresis (2-DE followed by image analysis to determine the extent of the effect c-Myc has on the cell and the proteins involved to give the new phenotype. Results Over 100 proteins that were differentially expressed in cMycCHO cells were detected with high statistical confidence, of which 41 were subsequently identified by tandem mass spectrometry (LC-MS/MS. Further analysis revealed proteins involved in a variety of pathways. Some examples of changes in protein expression include: an increase in nucleolin, involved in proliferation and known to aid in stabilising anti-apoptotic protein mRNA levels, the cytoskeleton and mitochondrial morphology (vimentin, protein biosysnthesis (eIF6 and energy metabolism (ATP synthetase, and a decreased regulation of all proteins, indentified, involved in matrix and cell to cell adhesion. Conclusion These results indicate several proteins involved in proliferation and adhesion that could be useful for future approaches to improve proliferation and decrease adhesion of CHO cell lines which are difficult to adapt to suspension culture.

Role of salicylic acid in resistance to cadmium stress in plants.

Science.gov (United States)

Liu, Zhouping; Ding, Yanfei; Wang, Feijuan; Ye, Yaoyao; Zhu, Cheng

2016-04-01

We review and introduce the importance of salicylic acid in plants under cadmium stress, and provide insights into potential regulatory mechanisms for alleviating cadmium toxicity. Cadmium (Cd) is a widespread and potentially toxic environmental pollutant, originating mainly from rapid industrial processes, the application of fertilizers, manures and sewage sludge, and urban activities. It is easily taken up by plants, resulting in obvious toxicity symptoms, including growth retardation, leaf chlorosis, leaf and root necrosis, altered structures and ultrastructures, inhibition of photosynthesis, and cell death. Therefore, alleviating Cd toxicity in plants is a major aim of plant research. Salicylic acid (SA) is a ubiquitous plant phenolic compound that has been used in many plant species to alleviate Cd toxicity by regulating plant growth, reducing Cd uptake and distribution in plants, protecting membrane integrity and stability, scavenging reactive oxygen species and enhancing antioxidant defense system, improving photosynthetic capacity. Furthermore, SA functions as a signaling molecule involved in the expression of several important genes. Significant amounts of research have focused on understanding SA functions and signaling in plants under Cd stress, but several questions still remain unanswered. In this article, the influence of SA on Cd-induced stress in plants and the potential regulation mechanism for alleviating Cd toxicity are reviewed.

The emerging CHO systems biology era: harnessing the ‘omics revolution for biotechnology

DEFF Research Database (Denmark)

Kildegaard, Helene Faustrup; Baycin-Hizal, Deniz; Lewis, Nathan

2013-01-01

into mathematical models that describe CHO phenotypes will provide crucial biotechnology insights. As ‘omics technologies and computational systems biology mature, genome-scale approaches will lead to major innovations in cell line development and metabolic engineering, thereby improving protein production......Chinese hamster ovary (CHO) cells are the primary factories for biopharmaceuticals because of their capacity to correctly fold and post-translationally modify recombinant proteins compatible with humans. New opportunities are arising to enhance these cell factories, especially since the CHO-K1 cell...

Isolation, identification and cadmium adsorption of a high cadmium ...

African Journals Online (AJOL)

GREGORY

2010-09-27

Sep 27, 2010 ... 1School of Minerals Processing and Bioengineering, Central South University, Changsha, ... Cadmium is a non-essential ... (1994) reported that cadmium might interact ... uptake of cadmium, lead and mercury (Svecova et al.,.

Development of autochthonous microbial consortia for enhanced phytoremediation of salt-marsh sediments contaminated with cadmium

International Nuclear Information System (INIS)

Teixeira, Catarina; Almeida, C. Marisa R.; Nunes da Silva, Marta; Bordalo, Adriano A.; Mucha, Ana P.

2014-01-01

Microbial assisted phytoremediation is a promising, though yet poorly explored, new remediation technique. The aim of this study was to develop autochthonous microbial consortia resistant to cadmium that could enhance phytoremediation of salt-marsh sediments contaminated with this metal. The microbial consortia were selectively enriched from rhizosediments colonized by Juncus maritimus and Phragmites australis. The obtained consortia presented similar microbial abundance but a fairly different community structure, showing that the microbial community was a function of the sediment from which the consortia were enriched. The effect of the bioaugmentation with the developed consortia on cadmium uptake, and the microbial community structure associated to the different sediments were assessed using a microcosm experiment. Our results showed that the addition of the cadmium resistant microbial consortia increased J. maritimus metal phytostabilization capacity. On the other hand, in P. australis, microbial consortia amendment promoted metal phytoextraction. The addition of the consortia did not alter the bacterial structure present in the sediments at the end of the experiments. This study provides new evidences that the development of autochthonous microbial consortia for enhanced phytoremediation of salt-marsh sediments contaminated with cadmium might be a simple, efficient, and environmental friendly remediation procedure. Capsule abstract: Development of autochthonous microbial consortia resistant to cadmium that enhanced phytoremediation by salt-marsh plants, without a long term effect on sediment bacterial diversity. - Highlights: • Cd resistant microbial consortia were developed and applied to salt-marsh sediments. • In Phragmites australis the consortia amendment promoted metal phytoextraction. • The consortia addition increased Juncus maritimus phytostabilization capacity. • No long term changes on the rhizosediment bacterial structure were observed

Development of autochthonous microbial consortia for enhanced phytoremediation of salt-marsh sediments contaminated with cadmium

Energy Technology Data Exchange (ETDEWEB)

Teixeira, Catarina [Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Universidade do Porto, Rua dos Bragas, 289, 4050-123 Porto (Portugal); Laboratório de Hidrobiologia e Ecologia, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto (Portugal); Almeida, C. Marisa R.; Nunes da Silva, Marta [Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Universidade do Porto, Rua dos Bragas, 289, 4050-123 Porto (Portugal); Bordalo, Adriano A. [Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Universidade do Porto, Rua dos Bragas, 289, 4050-123 Porto (Portugal); Laboratório de Hidrobiologia e Ecologia, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto (Portugal); Mucha, Ana P., E-mail: amucha@ciimar.up.pt [Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Universidade do Porto, Rua dos Bragas, 289, 4050-123 Porto (Portugal)

2014-09-15

Microbial assisted phytoremediation is a promising, though yet poorly explored, new remediation technique. The aim of this study was to develop autochthonous microbial consortia resistant to cadmium that could enhance phytoremediation of salt-marsh sediments contaminated with this metal. The microbial consortia were selectively enriched from rhizosediments colonized by Juncus maritimus and Phragmites australis. The obtained consortia presented similar microbial abundance but a fairly different community structure, showing that the microbial community was a function of the sediment from which the consortia were enriched. The effect of the bioaugmentation with the developed consortia on cadmium uptake, and the microbial community structure associated to the different sediments were assessed using a microcosm experiment. Our results showed that the addition of the cadmium resistant microbial consortia increased J. maritimus metal phytostabilization capacity. On the other hand, in P. australis, microbial consortia amendment promoted metal phytoextraction. The addition of the consortia did not alter the bacterial structure present in the sediments at the end of the experiments. This study provides new evidences that the development of autochthonous microbial consortia for enhanced phytoremediation of salt-marsh sediments contaminated with cadmium might be a simple, efficient, and environmental friendly remediation procedure. Capsule abstract: Development of autochthonous microbial consortia resistant to cadmium that enhanced phytoremediation by salt-marsh plants, without a long term effect on sediment bacterial diversity. - Highlights: • Cd resistant microbial consortia were developed and applied to salt-marsh sediments. • In Phragmites australis the consortia amendment promoted metal phytoextraction. • The consortia addition increased Juncus maritimus phytostabilization capacity. • No long term changes on the rhizosediment bacterial structure were observed.

Sequencing the CHO DXB11 genome reveals regional variations in genomic stability and haploidy

DEFF Research Database (Denmark)

Kaas, Christian Schrøder; Kristensen, Claus; Betenbaugh, Michael J.

2015-01-01

Background: The DHFR negative CHO DXB11 cell line (also known as DUX-B11 and DUKX) was historically the first CHO cell line to be used for large scale production of heterologous proteins and is still used for production of a number of complex proteins.  Results: Here we present the genomic sequence...... of the CHO DXB11 genome sequenced to a depth of 33x. Overall a significant genomic drift was seen favoring GC -> AT point mutations in line with the chemical mutagenesis strategy used for generation of the cell line. The sequencing depth for each gene in the genome revealed distinct peaks at sequencing...... in eight additional analyzed CHO genomes (15-20% haploidy) but not in the genome of the Chinese hamster. The dhfr gene is confirmed to be haploid in CHO DXB11; transcriptionally active and the remaining allele contains a G410C point mutation causing a Thr137Arg missense mutation. We find similar to 2...

Metaphase chromosome and nucleoid differences between CHO-K1 and its radiosensitive derivative xrs-5

International Nuclear Information System (INIS)

Schwartz, J.L.; Stephens, J.; Vaughan, A.T.M.

1992-05-01

The Chinese hamster ovary (CHO) cell line xrs-5 is a radiation-sensitive mutant isolated from CHO-K1 cells. The radiation sensitivity is associated with a defect in DNA double-strand break rejoining. Chromatin structure also appears altered in xrs-5 cells compared to the parental CHO-K1 cells. Metaphase chromosomes from xrs-5 are more condensed in appearance than CHO-K1 chromosomes. The overcondensed look is not the result of colcemid sensitivity. Electron microscopy studies suggest that xrs-5 metaphase chromosomes have larger loops of chromatin extending out from the chromosome core. There are also differences between CHO-K1 and xrs-5 cells in the size and fluorescence pattern of ethidium bromide-stained nucleoid preparations. These results suggest that there is a fundamental difference between CHO-K1 and xrs-5 in either the organization of the supercoiled loops of DNA attached to the nuclear matrix or in the nature of the proteins that attach the DNA to the matrix. These alterations in chromosome structure may underlie, in part, the radiation sensitivity of xrs-5 cells

Metaphase chromosome and nucleoid differences between CHO-K1 and its radiosensitive derivative xrs-5

International Nuclear Information System (INIS)

Schwartz, J.L.; Stephens, J.; Vaughan, A.T.M.

1993-01-01

The Chinese hamster ovary (CHO) cell line xrs-5 is a radiation-sensitive mutant isolated from CHO-K1 cells. The radiosensitivity is associated with a defect in DNA double-strand break rejoining. Chromatin structure also appears altered in xrs-5 cells compared with the parental CHO-K1 cells. Metaphase chromosomes form xrs-5 are more condensed in appearance than CHO-K1 chromosomes. The overcondensed look is not the result of colcemid sensitivity. Electron microscopy studies suggest that xrs-5 metaphase chromosomes have larger loops of chromatin extending out from the chromosome core. There are also differences between CHO-K1 and xrs-5 cells in the size and fluorescence pattern of ethidium bromide-stained nucleoid preparations. These results suggest that there is a fundamental difference between CHO-K1 and xrs-5 in either the organization of the supercoiled loops of DNA attached to the nuclear matrix or in the nature of the proteins that attach the DNA to the matrix. These alterations in chromosome structure may underlie, in part the radiation sensitivity of xrs-5 cells. (Author)

ASC-J9 Suppresses Castration-Resistant Prostate Cancer Growth through Degradation of Full-length and Splice Variant Androgen Receptors

Directory of Open Access Journals (Sweden)

Shinichi Yamashita

2012-01-01

Full Text Available Early studies suggested androgen receptor (AR splice variants might contribute to the progression of prostate cancer (PCa into castration resistance. However, the therapeutic strategy to target these AR splice variants still remains unresolved. Through tissue survey of tumors from the same patients before and after castration resistance, we found that the expression of AR3, a major AR splice variant that lacks the AR ligand-binding domain, was substantially increased after castration resistance development. The currently used antiandrogen, Casodex, showed little growth suppression in CWR22Rv1 cells. Importantly, we found that AR degradation enhancer ASC-J9 could degrade both full-length (fAR and AR3 in CWR22Rv1 cells as well as in C4-2 and C81 cells with addition of AR3. The consequences of such degradation of both fAR and AR3 might then result in the inhibition of AR transcriptional activity and cell growth in vitro. More importantly, suppression of AR3 specifically by short-hairpin AR3 or degradation of AR3 by ASC-J9 resulted in suppression of AR transcriptional activity and cell growth in CWR22Rv1-fARKD (fAR knockdown cells in which DHT failed to induce, suggesting the importance of targeting AR3. Finally, we demonstrated the in vivo therapeutic effects of ASC-J9 by showing the inhibition of PCa growth using the xenografted model of CWR22Rv1 cells orthotopically implanted into castrated nude mice with undetectable serum testosterone. These results suggested that targeting both fAR- and AR3-mediated PCa growth by ASC-J9 may represent the novel therapeutic approach to suppress castration-resistant PCa. Successful clinical trials targeting both fAR and AR3 may help us to battle castration-resistant PCa in the future.

Analysis of Hepatitis C Virus Genotype 1b Resistance Variants in Japanese Patients Treated with Paritaprevir-Ritonavir and Ombitasvir.

Science.gov (United States)

Krishnan, Preethi; Schnell, Gretja; Tripathi, Rakesh; Beyer, Jill; Reisch, Thomas; Zhang, Xinyan; Setze, Carolyn; Rodrigues, Lino; Burroughs, Margaret; Redman, Rebecca; Chayama, Kazuaki; Kumada, Hiromitsu; Collins, Christine; Pilot-Matias, Tami

2016-02-01

Treatment of HCV genotype 1b (GT1b)-infected Japanese patients with paritaprevir (NS3/4A inhibitor boosted with ritonavir) and ombitasvir (NS5A inhibitor) in studies M12-536 and GIFT-I demonstrated high sustained virologic response (SVR) rates. The virologic failure rate was 3% (13/436) across the two studies. Analyses were conducted to evaluate the impact of baseline resistance-associated variants (RAVs) on treatment outcome and the emergence and persistence of RAVs in patients experiencing virologic failure. Baseline paritaprevir resistance-conferring variants in NS3 were infrequent, while Y93H in NS5A was the most prevalent ombitasvir resistance-conferring variant at baseline. A comparison of baseline prevalence of polymorphisms in Japanese and western patients showed that Q80L and S122G in NS3 and L28M, R30Q, and Y93H in NS5A were significantly more prevalent in Japanese patients. In the GIFT-I study, the prevalence of Y93H in NS5A varied between 13% and 21% depending on the deep-sequencing detection threshold. Among patients with Y93H comprising 40% of their preexisting viral population, the 24-week SVR (SVR24) rates were >99% (276/277), 93% (38/41), and 76% (25/33), respectively, indicating that the prevalence of Y93H within a patient's viral population is a good predictor of treatment response. The predominant RAVs at the time of virologic failure were D168A/V in NS3 and Y93H alone or in combination with other variants in NS5A. While levels of NS3 RAVs declined over time, NS5A RAVs persisted through posttreatment week 48. Results from these analyses are informative in understanding the resistance profile of an ombitasvir- plus paritaprevir/ritonavir-based regimen in Japanese GT1b-infected patients. Copyright © 2016 Krishnan et al.

Novel pathways for ameliorating the fitness cost of gentamicin resistant small colony variants

DEFF Research Database (Denmark)

Vestergaard, Martin; Paulander, Wilhelm Erik Axel; Leng, Bingfeng

2016-01-01

Small colony variants (SCVs) of the human pathogen Staphylococcus aureus are associated with persistent infections. Phenotypically, SCVs are characterized by slow growth and they can arise upon interruption of the electron transport chain that consequently reduce membrane potential and thereby...... limit uptake of aminoglycosides (e.g., gentamicin). In this study, we have examined the pathways by which the fitness cost of SCVs can be ameliorated. Five gentamicin resistant SCVs derived from S. aureus JE2 were independently selected on agar plates supplemented with gentamicin. The SCVs carried...... mutations in the menaquinone and hemin biosynthesis pathways, which caused a significant reduction in exponential growth rates relative to wild type (WT; 0.59-0.72) and reduced membrane potentials. Fifty independent lineages of the low-fitness, resistant mutants were serially passaged for up to 500...

Mechanisms of oxygen radiosensitization in CHO cells

International Nuclear Information System (INIS)

Whillans, D.W.

1981-01-01

A model is presented for repair and fixation pathways when CHO cells are irradiated in the presence of O 2 . This analysis predicts that an increase in the repair path such as has been postulated for addition of a radioprotective sulfhydryl should increase OER/sub max/ in porportion to k prime, the new repair rate constant and also increase K with k prime. Any radiosensitizer which mimics the action of O 2 simply increases k prime 2 , so that the OER/sub max/ decreases at 1/k prime 2 but K increases as k prime 2 . These predictions have been tested in mammalian CHO cells making use of a Clark-type oxygen probe with defined conditions to ensure that O 2 is not depleted by radiation or cellular consumption, and so O 2 levels are known with accuracy. In a complementary study, the technique of rapid-mixing was used to measure the rate of development of O 2 sensitization in these same cells. By a variation of this rapid-mixing approach, the rate of diffusion into these cells has also been measured independently. Neither the dependence of OER on O 2 concentration nor the development of radiosensitivity with time of incubation in O 2 gives evidence in CHO cells for two components of sensitization indicative of two sites or two mechanisms of action, as seen in some V79 sublines. 13 references, 4 figures

The vapour pressures over saturated aqueous solutions of cadmium chloride, cadmium bromide, cadmium iodide, cadmium nitrate, and cadmium sulphate

International Nuclear Information System (INIS)

Apelblat, Alexander; Korin, Eli

2007-01-01

Vapour pressures of water over saturated solutions of cadmium salts (chloride, bromide, iodide, nitrate, and sulphate) were determined over the temperature range 280 K to 322 K and compared with the literature data. The vapour pressures determined were used to obtain the water activities, osmotic coefficients and the molar enthalpies of vaporization in the (cadmium salt + water) systems

The vapour pressures over saturated aqueous solutions of cadmium chloride, cadmium bromide, cadmium iodide, cadmium nitrate, and cadmium sulphate

Energy Technology Data Exchange (ETDEWEB)

Apelblat, Alexander [Department of Chemical Engineering, Ben Gurion University of the Negev, P.O. Box 653, Beer Sheva 84105 (Israel)]. E-mail: apelblat@bgu.ac.il; Korin, Eli [Department of Chemical Engineering, Ben Gurion University of the Negev, P.O. Box 653, Beer Sheva 84105 (Israel)

2007-07-15

Vapour pressures of water over saturated solutions of cadmium salts (chloride, bromide, iodide, nitrate, and sulphate) were determined over the temperature range 280 K to 322 K and compared with the literature data. The vapour pressures determined were used to obtain the water activities, osmotic coefficients and the molar enthalpies of vaporization in the (cadmium salt + water) systems.

[Investigation of urinary cadmium reference of general population in two rural high background areas of soil cadmium and non-cadmium-polluted in China].

Science.gov (United States)

Han, Jingxiu; Li, Qiujuan; Yao, Dancheng; Zheng, Jiangang; Zhang, Wenli; Shang, Qi

2014-09-01

To study the reference of urinary. cadmium of the general population in rural high background areas of soil cadmium and non-cadmium contaminated in China. In rural high background areas of soil cadmium and non-cadmium contaminated, randomly selected non-occupational-cadmium exposed population 1134 people (male 519, female 615) with each gender and age groups, questionnaire surveyed and collected random urine. Urinary cadmium and urinary creatinine (Cr) concentration were tested, excluding urinary Cr 3 g/L. Analyze the impact factors of urinary cadmium and calculated 95% quantile (P,95 ) of urinary cadmium after correction by urinary Cr. Female median urinary cadmium was significantly higher than men, male smokers median urinary cadmium was significantly higher than male non-smokers (P 30 year-old. According to gender, and 15 -30, 30 years old, analysis the upper limit of cadmium in urine. The 95% upper limit of urinary cadmium of 30 year-old female (12.24 microg/gCr) was significantly higher than other populations ( population exceeded the upper limit (5 microg/gCr) of the occupational cadmium poisoning diagnostic criteria in China (GBZ 17-2002). In the two rural high background areas of soil cadmium and non-cadmium polluted , urinary cadmium reference of non-cadmium-occupational-exposed male is <9.0 microg/gCr, and female <13.0 microg/gCr.

Complete genome sequence of Vibrio anguillarum phage CHOED successfully used for phage therapy in aquaculture

DEFF Research Database (Denmark)

Romero, Jaime; Higuera, Gastón; Gajardo, Felipe

2014-01-01

Vibrio anguillarum phage CHOED was isolated from Chilean mussels. It is a virulent phage showing effective inhibition of V. anguillarum. CHOED has potential in phage therapy, because it can protect fish from vibriosis in fish farms. Here, we announce the completely sequenced genome of V....... anguillarum phage CHOED....

SB-224289 Antagonizes the Antifungal Mechanism of the Marine Depsipeptide Papuamide A.

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Chelsi D Cassilly

Full Text Available In order to expand the repertoire of antifungal compounds a novel, high-throughput phenotypic drug screen targeting fungal phosphatidylserine (PS synthase (Cho1p was developed based on antagonism of the toxin papuamide A (Pap-A. Pap-A is a cyclic depsipeptide that binds to PS in the membrane of wild-type Candida albicans, and permeabilizes its plasma membrane, ultimately causing cell death. Organisms with a homozygous deletion of the CHO1 gene (cho1ΔΔ do not produce PS and are able to survive in the presence of Pap-A. Using this phenotype (i.e. resistance to Pap-A as an indicator of Cho1p inhibition, we screened over 5,600 small molecules for Pap-A resistance and identified SB-224289 as a positive hit. SB-224289, previously reported as a selective human 5-HT1B receptor antagonist, also confers resistance to the similar toxin theopapuamide (TPap-A, but not to other cytotoxic depsipeptides tested. Structurally similar molecules and truncated variants of SB-224289 do not confer resistance to Pap-A, suggesting that the toxin-blocking ability of SB-224289 is very specific. Further biochemical characterization revealed that SB-224289 does not inhibit Cho1p, indicating that Pap-A resistance is conferred by another undetermined mechanism. Although the mode of resistance is unclear, interaction between SB-224289 and Pap-A or TPap-A suggests this screening assay could be adapted for discovering other compounds which could antagonize the effects of other environmentally- or medically-relevant depsipeptide toxins.

Organo-Zintl-based superatoms: [Ge9(CHO)3] and [Ge9(CHO)

Science.gov (United States)

Reddy, G. Naaresh; Jena, Puru; Giri, Santanab

2017-10-01

A systematic study, based on density functional theory and different hybrid functionals for exchange-correlation potential, shows that the electron affinities of organo-zintl clusters [Ge9(R)n] [R = CHO; n = 1, 3] are close to that of chlorine (3.6 eV) and iodine (3.0 eV). A detailed study of the molecular orbitals of these complexes, when compared to those of Al13-, Cl- and I-, confirm that they behave as superatoms, mimicking the chemistry of halogens. This study expands the scope of superatoms by including a new class of pseudo-halogens based on ligated organo-Zintl ions.

Characterization and radiation response of a heat-resistant variant of V79 cells

International Nuclear Information System (INIS)

Campbell, S.D.; Kruuv, J.; Lepock, J.R.

1983-01-01

A thermoresistant variant of the established cell line V79-S171-W1 was isolated after treatment with nitrosoguanidine and repeated heat treatments at 42.6 to 43 degrees C, and showed an enhanced ability to survive at 42.6, 43.5, and 44.5 degrees C. The rates of inactivation of the normal and heat-resistant lines differed by approximately a factor of 2 over this temperature range. This level of thermoresistance was stable for the first 80 doublings, but was lost by 120 doublings. This may have been due to a reversion to the normal V79 line since there was no continuous selection pressure and the thermoresistant variant, which was designated at HR7, had a longer average doubling time. Transient thermotolerance was induced in both the V79 and HR7 cells by a 10-min exposure to 44.5 degrees C. After 3 hr incubation at 37 degrees C, both cell lines had an identical sensitivity to further exposure to 44.5 degrees C. Thus the long-term thermoresistance of the HR7 cells may be due to a permanent induction of a low level of thermotolerance. The (ionizing) radiation survival curves and the ability to repair sublethal radiation damage were identical for the thermoresistant variant and the parent cell line

Enhanced Cadmium (Cd Phytoextraction from Contaminated Soil using Cd-Resistant Bacterium

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Kunchaya Setkit

2014-01-01

Full Text Available A cadmium (Cd-resistant bacterium, Micrococcus sp. MU1, is able to produce indole-3-acetic acid and promotes root elongation and plant growth. The potential of this bacterium on enhancement of Cd uptake and bioaccumulation of Cd in Helianthus annuus L. planted in Cd-contaminated soil was evaluated in greenhouse condition. The results showed that Micrococcus sp. MU1promoted the growth of H. annuus L. by increasing the root length, stem height, dry biomass, root to shoot ratio and also significantly increased Cd accumulation in the root and above-ground tissues of H. annuus L. compared to uninoculated control. Re-inoculation with Micrococcus sp. MU1in contaminated soil helped in promoting plant growth and Cd phytoextraction throughout the cultivation period. In addition, phytoextraction coefficient and translocation factor (TF of H. annuus L. inoculated with Micrococcus sp. MU1were higher than that of uninoculated control and TF continuously increased with time. Our results suggested that Micrococcus sp. MU1 has an ability to enhance plant growth and Cd uptake in H. annuus L. Synergistic interaction between Micrococcus sp. MU1 and H. annuus L. could be further applied for Cd phytoextraction in polluted areas.

CHO glyco-engineering using CRISPR/Cas9 multiplexing for protein production with homogeneous N-glycan profiles

DEFF Research Database (Denmark)

Amann, Thomas; Hansen, Anders Holmgaard; Pristovsek, Nusa

Combining the chinese hamster ovary (CHO) - K1 draft genome1,2, identified CHO glycosyltransferases3 and the power of multiplexing gene knock-outs with CRISPR/Cas94 via co-transfection of Cas9 and one single guiding RNA (sgRNA) per target, we generated 20 Rituximab expressing CHO-S cell lines...

Strong CH/O interactions between polycyclic aromatic hydrocarbons and water: Influence of aromatic system size.

Science.gov (United States)

Veljković, Dušan Ž

2018-03-01

Energies of CH/O interactions between water molecule and polycyclic aromatic hydrocarbons with a different number of aromatic rings were calculated using ab initio calculations at MP2/cc-PVTZ level. Results show that an additional aromatic ring in structure of polycyclic aromatic hydrocarbons significantly strengthens CH/O interactions. Calculated interaction energies in optimized structures of the most stable tetracene/water complex is -2.27 kcal/mol, anthracene/water is -2.13 kcal/mol and naphthalene/water is -1.97 kcal/mol. These interactions are stronger than CH/O contacts in benzene/water complex (-1.44 kcal/mol) while CH/O contacts in tetracene/water complex are even stronger than CH/O contacts in pyridine/water complexes (-2.21 kcal/mol). Electrostatic potential maps for different polycyclic aromatic hydrocarbons were calculated and used to explain trends in the energies of interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

Dynamic of cadmium accumulation in the internal organs of rats after exposure to cadmium chloride and cadmium sulphide nanoparticules of various sizes

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Apykhtina O.L.

2017-06-01

Full Text Available The article presents the results of study of cadmium accumulation in the internal organs of Wistar rats after prolonged intraperitoneal administration of cadmium chloride and cadmium sulphide nanoparticles of 4-6 nm and 9-11 nm in size in a dose of 0.08 mg /kg/day calculated as cadmium. Toxic effects were evaluated after 30 injections (1.5 months, 60 injections (3 months, and 1.5 months after the exposure has been ceased. The results of the study showed that the most intensive accumulation of cadmium was observed in the kidneys and liver of experimental animals, which is due to the peculiarities of the toxicokinetics and the route of administration of cadmium compounds. In the kidneys, spleen and thymus of animals exposed to cadmium sulphide nanoparticles, a greater concentration of cadmium than in the organs of animals exposed to cadmium chloride was found. Cadmium accumulated more intensively in the spleen after exposure to larger nanoparticles, than in the kidneys and thymus. In the liver, heart, aorta and brain significant accumulation was observed after cadmium chloride exposure.

Cadmium and renal cancer

International Nuclear Information System (INIS)

Il'yasova, Dora; Schwartz, Gary G.

2005-01-01

Background: Rates of renal cancer have increased steadily during the past two decades, and these increases are not explicable solely by advances in imaging modalities. Cadmium, a widespread environmental pollutant, is a carcinogen that accumulates in the kidney cortex and is a cause of end-stage renal disease. Several observations suggest that cadmium may be a cause of renal cancer. Methods: We performed a systematic review of the literature on cadmium and renal cancer using MEDLINE for the years 1966-2003. We reviewed seven epidemiological and eleven clinical studies. Results: Despite different methodologies, three large epidemiologic studies indicate that occupational exposure to cadmium is associated with increased risk renal cancer, with odds ratios varying from 1.2 to 5.0. Six of seven studies that compared the cadmium content of kidneys from patients with kidney cancer to that of patients without kidney cancer found lower concentrations of cadmium in renal cancer tissues. Conclusions: Exposure to cadmium appears to be associated with renal cancer, although this conclusion is tempered by the inability of studies to assess cumulative cadmium exposure from all sources including smoking and diet. The paradoxical findings of lower cadmium content in kidney tissues from patients with renal cancer may be caused by dilution of cadmium in rapidly dividing cells. This and other methodological problems limit the interpretation of studies of cadmium in clinical samples. Whether cadmium is a cause of renal cancer may be answered more definitively by future studies that employ biomarkers of cadmium exposure, such as cadmium levels in blood and urine

Couinaud's classification v.s. Cho's classification. Their feasibility in the right hepatic lobe

International Nuclear Information System (INIS)

Shioyama, Yasukazu; Ikeda, Hiroaki; Sato, Motohito; Yoshimi, Fuyo; Kishi, Kazushi; Sato, Morio; Kimura, Masashi

2008-01-01

The objective of this study was to investigate if the new classification system proposed by Cho is feasible to clinical usage comparing with the classical Couinaud's one. One hundred consecutive cases of abdominal CT were studied using a 64 or an 8 slice multislice CT and created three dimensional portal vein images for analysis by the Workstation. We applied both Cho's classification and the classical Couinaud's one for each cases according to their definitions. Three diagnostic radiologists assessed their feasibility as category one (unable to classify) to five (clear to classify with total suit with the original classification criteria). And in each cases, we tried to judge whether Cho's or the classical Couinaud' classification could more easily transmit anatomical information. Analyzers could classified portal veins clearly (category 5) in 77 to 80% of cases and clearly (category 5) or almost clearly (category 4) in 86-93% along with both classifications. In the feasibility of classification, there was no statistically significant difference between two classifications. In 15 cases we felt that using Couinaud's classification is more convenient for us to transmit anatomical information to physicians than using Cho's one, because in these cases we noticed two large portal veins ramify from right main portal vein cranialy and caudaly and then we could not classify P5 as a branch of antero-ventral segment (AVS). Conversely in 17 cases we felt Cho's classification is more convenient because we could not divide right posterior branch as P6 and P7 and in these cases the right posterior portal vein ramified to several small branches. The anterior fissure vein was clearly noticed in only 60 cases. Comparing the classical Couinaud's classification and Cho's one in feasility of classification, there was no statistically significant difference. We propose we routinely report hepatic anatomy with the classical Couinauds classification and in the preoperative cases we

Preparation and characterization of polyaniline-cadmium sulfide nanocomposite for gas sensor application

Science.gov (United States)

Al-Jawad, Selma M. H.; Rafic, Sewench N.; Muhsen, Mustafa M.

2017-09-01

Polyaniline (PANI) was prepared by chemical oxidative polymerization of aniline monomers as emeraldine salt form. By the same method, polyaniline-cadmium sulfide nanocomposites were synthesized in the presence of different percentages (10-50 wt.%) of cadmium sulfide (CdS) which was prepared by using sol-gel method. The optical band gap was decrease with increasing of CdS concentration, that is obtained from UV-VIS measurements. From SEM and AFM, there is uniform distribution for cadmium sulfide nanoparticles in the PANI matrix. The electrical measurements of nanocomposites exhibit the effect of crystallite size and the high resistivity of CdS on the resistivity of nanocomposites. Emeraldine salt PANI, CdS and PANI-CdS nanocomposites were investigated as gas sensors. From this investigation, the sensitivity of PANI-CdS for NO2 gas increase with the increasing of operation temperature and the optimum sensitivity was obtained at 200∘C. The sensitivity of nanocomposites at best temperature (200∘C) was increased and faster response time with the increasing of CdS contents.

The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line

DEFF Research Database (Denmark)

Xu, Xun; Pan, Shengkai; Liu, Xin

2011-01-01

Chinese hamster ovary (CHO)-derived cell lines are the preferred host cells for the production of therapeutic proteins. Here we present a draft genomic sequence of the CHO-K1 ancestral cell line. The assembly comprises 2.45 Gb of genomic sequence, with 24,383 predicted genes. We associate most of...

Thermal radiosensitization in heat- and radiation-sensitive mutants of CHO cells

International Nuclear Information System (INIS)

Kampinga, H.H.; Kanon, B.; Konings, A.W.T.; Stackhouse, M.A.; Bedford, J.S.

1993-01-01

In the current study, the extent of hyperthermic radiosensitization in a new γ-radiation-sensitive cell line, irs-20, recently isolated by Stackhouse and Bedford (1991) and a heat-sensitive mutant hs-36 (Harvey and Bedford 1988) was compared with the radiosensitization of their mutual parent CHO 10B12 cell line. The irs-20 and CHO 10B12 cells have comparable heat (43.5 o C) sensitivities, whereas hs-36 and CHO 10B12 show a similar sensitivity to γ- and X-rays. Radiosensitization due to pre-exposure to 43.5 o C heating of plateau phase cultures was found for all three cell lines, even after relatively mild heat treatment killing <20% of cells. Experiments using CHEF electrophoresis confirmed the dsb repair deficiency of the irs-20 cells (Stackhouse and Bedford 1992) and showed that heat inhibited dsb repair in all three cell lines. (Author)

Repair-deficient xeroderma pigmentosum cells made UV light resistant by fusion with X-ray-inactivated Chinese hamster cells

International Nuclear Information System (INIS)

Karentz, D.; Cleaver, J.E.

1986-01-01

Xeroderma pigmentosum (XP) is an autosomal recessive human disease, characterized by an extreme sensitivity to sunlight, caused by the inability of cells to repair UV light-induced damage to DNA. Cell fusion was used to transfer fragments of Chinese hamster ovary (CHO) chromosomes into XP cells. The hybrid cells exhibited UV resistance and DNA repair characteristics comparable to those expressed by CHO cells, and their DNA had greater homology with CHO DNA than did the DNA from XP cells. Control experiments consisted of fusion of irradiated and unirradiated XP cells and repeated exposure of unfused XP cells to UV doses used for hybrid selection. These treatments did not result in an increase in UV resistance, repair capability, or homology with CHO DNA. The hybrid cell lines do not, therefore, appear to be XP revertants. The establishment of these stable hybrid cell lines is an initial step toward identifying and cloning CHO DNA repair genes that complement the XP defect in human cells. The method should also be applicable to cloning genes for other diseases, such as ataxia-telangiectasia and Fanconi's anemia

Cadmium accumulation by Axonopus compressus (Sw.) P. Beauv and Cyperus rotundas Linn growing in cadmium solution and cadmium-zinc contaminated soil

OpenAIRE

Paitip Thiravetyan; Vibol Sao; Woranan Nakbanpote

2007-01-01

This research investigated the phyto-remediation potentials of Cyperus rotundas Linn (Nutgrass) and Axonopus compressus (Sw.) P. Beauv (Carpetgrass) for cadmium removal from cadmium solution andcadmium-zinc contaminated soil. Plants growth in the solution showed that cadmium decreased the relative growth rate of both grasses. However, the amount of cadmium accumulated in shoot and root was increasedwith the increase in cadmium concentration and exposure time. Growth in fertile soil mixed with...

Stable Human Hepatoma Cell Lines for Efficient Regulated Expression of Nucleoside/Nucleotide Analog Resistant and Vaccine Escape Hepatitis B Virus Variants and Woolly Monkey Hepatitis B Virus.

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Xin Cheng

Full Text Available Hepatitis B virus (HBV causes acute and chronic hepatitis B (CHB. Due to its error-prone replication via reverse transcription, HBV can rapidly evolve variants that escape vaccination and/or become resistant to CHB treatment with nucleoside/nucleotide analogs (NAs. This is particularly problematic for the first generation NAs lamivudine and adefovir. Though now superseded by more potent NAs, both are still widely used. Furthermore, resistance against the older NAs can contribute to cross-resistance against more advanced NAs. For lack of feasible HBV infection systems, the biology of such variants is not well understood. From the recent discovery of Na+-taurocholate cotransporting polypeptide (NTCP as an HBV receptor new in vitro infection systems are emerging, yet access to the required large amounts of virions, in particular variants, remains a limiting factor. Stably HBV producing cell lines address both issues by allowing to study intracellular viral replication and as a permanent source of defined virions. Accordingly, we generated a panel of new tetracycline regulated TetOFF HepG2 hepatoma cell lines which produce six lamivudine and adefovir resistance-associated and two vaccine escape variants of HBV as well as the model virus woolly monkey HBV (WMHBV. The cell line-borne viruses reproduced the expected NA resistance profiles and all were equally sensitive against a non-NA drug. The new cell lines should be valuable to investigate under standardized conditions HBV resistance and cross-resistance. With titers of secreted virions reaching >3 x 10(7 viral genome equivalents per ml they should also facilitate exploitation of the new in vitro infection systems.

Cadmium accumulation by Axonopus compressus (Sw. P. Beauv and Cyperus rotundas Linn growing in cadmium solution and cadmium-zinc contaminated soil

Directory of Open Access Journals (Sweden)

Paitip Thiravetyan

2007-05-01

Full Text Available This research investigated the phyto-remediation potentials of Cyperus rotundas Linn (Nutgrass and Axonopus compressus (Sw. P. Beauv (Carpetgrass for cadmium removal from cadmium solution andcadmium-zinc contaminated soil. Plants growth in the solution showed that cadmium decreased the relative growth rate of both grasses. However, the amount of cadmium accumulated in shoot and root was increasedwith the increase in cadmium concentration and exposure time. Growth in fertile soil mixed with Cd-contaminated zinc silicate residue (65% Si, 19% Ca, 2% Zn, 1% Mg and 0.03% Cd at the ratio of 50:50 (w/wfor 30 days showed that C. rotundas Linn accumulated cadmium in root and shoot to 2,178 and 1,144 mg kg-1 dry weight, respectively. A. compressus (Sw. P. Beauv accumulated cadmium in root and shoot to 1,965and 669 mg kg-1 dry weight, respectively. Scanning electron microscope connected to energy-dispersive X-ray spectroscopy suggested that the mechanism of cadmium accumulation by both grasses involved thecadmium precipitation in the stable form of cadmium silicate, which indicated that C. rotundas Linn and A. compressus (Sw. P. Beauv could be grown to prevent soil erosion and to remediate cadmium-contaminatedsoil.

Postnatal Expression of V2 Vasopressin Receptor Splice Variants in the Rat Cerebellum

Science.gov (United States)

Vargas, Karina J.; Sarmiento, José M.; Ehrenfeld, Pamela; Añazco, Carolina C.; Villanueva, Carolina I.; Carmona, Pamela L.; Brenet, Marianne; Navarro, Javier; Müller-Esterl, Werner; Figueroa, Carlos D.; González, Carlos B.

2010-01-01

The V2 vasopressin receptor gene contains an alternative splice site in exon-3, which leads to the generation of two splice variants (V2a and V2b) first identified in the kidney. The open reading frame of the alternatively spliced V2b transcripten codes a truncated receptor, showing the same amino acid sequence as the canonical V2a receptor up to the 6th transmembrane segment, but displaying a distinct sequence to the corresponding 7th transmembrane segment and C-terminal domain relative to the V2a receptor. Here, we demonstrate the postnatal expression of V2a and V2b variants in the rat cerebellum. Most importantly, we showed by in situ hybridization and immunocytochemistry that both V2 splice variants were preferentially expressed in Purkinje cells, from early to late postnatal development. In addition, both variants were transiently expressed in the neuroblastic external granule cells and Bergmann fibers. These results indicate that the cellular distributions of both splice variants are developmentally regulated, and suggest that the transient expression of the V2 receptor is involved in the mechanisms of cerebellar cytodifferentiation by AVP. Finally, transfected CHO-K1 .expressing similar amounts of both V2 splice variants, as that found in the cerebellum, showed a significant reduction in the surface expression of V2a receptors, suggesting that the differential expression of the V2 splice variants regulate the vasopressin signaling in the cerebellum. PMID:19281786

Cholesterol oxidase (ChoE) is not important in the virulence of Rhodococcus equi.

Science.gov (United States)

Pei, Yanlong; Dupont, Chris; Sydor, Tobias; Haas, Albert; Prescott, John F

2006-12-20

To analyze further the role in virulence of the prominent cholesterol oxidase (ChoE) of Rhodococcus equi, an allelic exchange choE mutant from strain 103+ was constructed and assessed for virulence in macrophages, in mice, and in foals. There was no difference between the mutant and parent strain in cytotoxic activity for macrophages or in intra-macrophage multiplication. No evidence of attenuation was obtained in macrophages and in mice, but there was slight attenuation apparent in four intra-bronchially infected foals compared to infection of four foals with the virulent parent strain, based on a delayed rise in temperature of the choE-mutant infected foals. However, bacterial colony counts in the lung 2 weeks after infection were not significantly different, although there was a slight but non-significant (P=0.12) difference in lung:body weight ratio of the choE mutant versus virulent parent infected foals (mean 2.67+/-0.25% compared to 4.58+/-0.96%). We conclude that the cholesterol oxidase is not important for the virulence of R. equi.

Radiation response of drug-resistant variants of a human breast cancer cell line

International Nuclear Information System (INIS)

Lehnert, S.; Greene, D.; Batist, G.

1989-01-01

The radiation response of drug-resistant variants of the human tumor breast cancer cell line MCF-7 has been investigated. Two sublines, one resistant to adriamycin (ADRR) and the other to melphalan (MLNR), have been selected by exposure to stepwise increasing concentrations of the respective drugs. ADRR cells are 200-fold resistant to adriamycin and cross-resistant to a number of other drugs and are characterized by the presence of elevated levels of selenium-dependent glutathione peroxidase and glutathione-S-transferase. MLNR cells are fourfold resistant to melphalan and cross-resistant to some other drugs. The only mechanism of drug resistance established for MLNR cells to date is an enhancement of DNA excision repair processes. While the spectrum of drug resistance and the underlying mechanisms differ for the two sublines, their response to radiation is qualitatively similar. Radiation survival curves for ADRR and MLNR cells differ from that for wild-type cells in a complex manner with, for the linear-quadratic model, a decrease in the size of alpha and an increase in the size of beta. There is a concomitant decrease in the size of the alpha/beta ratio which is greater for ADRR cells than for MLNR cells. Analysis of results using the multitarget model gave values of D0 of 1.48, 1.43, and 1.67 Gy for MCF-7 cells are not a consequence of cell kinetic differences between these sublines. Results of split-dose experiments indicated that for both drug-resistant sublines the extent of sublethal damage repair reflected the width of the shoulder on the single-dose survival curve. For MCF-7 cells in the stationary phase of growth, the drug-resistant sublines did not show cross-resistance to radiation; however, delayed subculture following irradiation of stationary-phase cultures increased survival to a greater extent for ADRR and MLNR cells than for wild-type cells

Cadmium, an environmental poison

Energy Technology Data Exchange (ETDEWEB)

Oestergaard, A K

1974-04-15

In recent years, industrial employment of cadmium has increased considerably. Cadmium is now present in the environment and has caused acute and chronic poisoning. Inhalation of cadmium vapor or dust causes pulmonary damage while the kidney is the critical organ in absorption of cadmium. The element accumulates in the kidney and causes tubular damage or 200 ppm in the renal cortex. In animal experiments, cadmium may cause raised blood pressure, sterility and malignant tumors. On account of the pronounced tendency of cadmium to accumulate and its toxicity, it is important to trace sources and to reduce exposure of the population. 62 references.

Cadmium and the kidney.

OpenAIRE

Friberg, L

1984-01-01

The paper is a review of certain aspects of importance of cadmium and the kidney regarding the assessment of risks and understanding of mechanisms of action. The review discusses the following topics: history and etiology of cadmium-induced kidney dysfunction and related disorders; cadmium metabolism, metallothionein and kidney dysfunction; cadmium in urine as indicator of body burden, exposure and kidney dysfunction; cadmium levels in kidney and liver as indicators of kidney dysfunction; cha...

Cadmium

NARCIS (Netherlands)

Meulenbelt, Jan

2017-01-01

Together with zinc and mercury, cadmium belongs to group IIb of the periodic table. It can be found in rocks, soil, water, coal, zinc ore, lead ore, and copper ore. In the environment, cadmium is present predominantly as the oxide or as the chloride, sulfide, or sulfate salt. It has no recognizable

Cadmium Bio sorption by Some Bacterial Isolates and Their Mutants Induced by gamma Radiation

International Nuclear Information System (INIS)

Tawfik, Z.S.; Elsonbaty, S.M.; Abdalla, N.M.

1999-01-01

Cadmium bio sorption by bacterial cells is recognized as a potential alternative to existing recovery technologies. Bacterial strains under investigation were isolated from air surrounding gamma industrial facility Co 60 source of the NCRRT, Cairo. The effect of different concentrations of cadmium on the growth was determined for the spore forming bacteria B.coagulans, B.megaterium, B.pumilus, B.pantothenticus, and also for Staphylo coccus aureus, the reference standard strain used in these study for comparison was B.subtilis MERK 10646. The results indicated that, B.pantothenticus was the most tolerant isolate, and it can resist up to 400 ppm. Cadmium capacity for B.subtilis parent strain was increased through the influence of different doses of gamma radiation, selected mutant of B.subtilis show enhanced level of cadmium accumulation. The effect of environmental parameters as ph, temperature and also the effect of biomass factor on cadmium uptake by B.pantothenticus and B.subtilis (m) was traced

Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission.

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Andrea Hauser

Full Text Available Pregnant HIV-infected women were screened for the development of HIV-1 drug resistance after implementation of a triple-antiretroviral transmission prophylaxis as recommended by the WHO in 2006. The study offered the opportunity to compare amplicon-based 454 ultra-deep sequencing (UDS and allele-specific real-time PCR (ASPCR for the detection of drug-resistant minor variants in the HIV-1 reverse transcriptase (RT.Plasma samples from 34 Tanzanian women were previously analysed by ASPCR for key resistance mutations in the viral RT selected by AZT, 3TC, and NVP (K70R, K103N, Y181C, M184V, T215Y/F. In this study, the RT region of the same samples was investigated by amplicon-based UDS for resistance mutations using the 454 GS FLX System.Drug-resistant HIV-variants were identified in 69% (20/29 of women by UDS and in 45% (13/29 by ASPCR. The absolute number of resistance mutations identified by UDS was twice that identified by ASPCR (45 vs 24. By UDS 14 of 24 ASPCR-detected resistance mutations were identified at the same position. The overall concordance between UDS and ASPCR was 61.0% (25/41. The proportions of variants quantified by UDS were approximately 2-3 times lower than by ASPCR. Amplicon generation from samples with viral loads below 20,000 copies/ml failed more frequently by UDS compared to ASPCR (limit of detection = 650 copies/ml, resulting in missing or insufficient sequence coverage.Both methods can provide useful information about drug-resistant minor HIV-1 variants. ASPCR has a higher sensitivity than UDS, but is restricted to single resistance mutations. In contrast, UDS is limited by its requirement for high viral loads to achieve sufficient sequence coverage, but the sequence information reveals the complete resistance patterns within the genomic region analysed. Improvements to the UDS limit of detection are in progress, and UDS could then facilitate monitoring of drug-resistant minor variants in the HIV-1 quasispecies.

Biosorption of Cadmium from Aqueous Solutions Using A local ...

African Journals Online (AJOL)

Cadmium (Cd) (II) resistant strain of a marine fungus, named Aspergillus cristatus was isolated from heavy metals polluted area in the Mediterranean Sea, Alexandria, Egypt during autumn, 2009. It could tolerate up to 100 mg l–1. Optimization of culture conditions for production of fungal biomass fortifying maximum Cd (II) ...

Flux of Cadmium through Euphausiids

International Nuclear Information System (INIS)

Benayoun, G.; Fowler, S.W.; Oregioni, B.

1976-01-01

Flux of the heavy metal cadmium through the euphausiid Meganyctiphanes norvegica was examined. Radiotracer experiments showed that cadmium can be accumulated either directly from water or through the food chain. When comparing equilibrium cadmium concentration factors based on stable element measurements with those obtained from radiotracer experiments, it is evident that exchange between cadmium in the water and that in euphausiid tissue is a relatively slow process, indicating that, in the long term, ingestion of cadmium will probably be the more important route for the accumulation of this metal. Approximately 10% of cadmium ingested by euphausiids was incorporated into internal tissues when the food source was radioactive Artemia. After 1 month cadmium, accumulated directly from water, was found to be most concentrated in the viscera with lesser amounts in eyes, exoskeleton and muscle, respectively. Use of a simple model, based on the assumption that cadmium taken in by the organism must equal cadmium released plus that accumulated in tissue, allowed assessment of the relative importance of various metabolic parameters in controlling the cadmium flux through euphausiids. Fecal pellets, due to their relatively high rate of production and high cadmium content, accounted for 84% of the total cadmium flux through M. norvegica. Comparisons of stable cadmium concentrations in natural euphausiid food and the organism's resultant fecal pellets indicate that the cadmium concentration in ingested material was increased nearly 5-fold during its passage through the euphausiid. From comparisons of all routes by which cadmium can be released from M. norvegica to the water column, it is concluded that fecal pellet deposition represents the principal mechanism effecting the downward vertical transport of cadmium by this species. (author)

Enhancement of Human Prolactin Synthesis by Sodium Butyrate Addition to Serum-Free CHO Cell Culture

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Herbert Rodrigues Goulart

2010-01-01

Full Text Available Sodium butyrate (NaBu has been used as a productivity enhancer for the synthesis of recombinant proteins in Chinese hamster ovary (CHO cells. Thus, the influence of NaBu on the production of recombinant human prolactin (hPRL from CHO cells was investigated for the first time. CHO cell cultures were submitted to a treatment with different concentrations of NaBu (0.25 to 4 mM. Quantitative and qualitative analyses by reverse-phase high-performance liquid chromatography (RP-HPLC and Western blot or SDS-PAGE, carried out directly on CHO-conditioned medium, showed that the highest hPRL expression was obtained with 1 mM NaBu. In vitro biological assays based on noble rat lymphoma (Nb2 and mouse pro-B lymphoma (Ba/F3-LLP cells were carried out on purified hPRL. Its bioactivity in the presence of NaBu was not apparently different from that of the First International Reference Reagent of recombinant hPRL (WHO 97/714. Our results show that NaBu increased the synthesis of recombinant hPRL in CHO cells, apparently without compromising either its structure or function.

Calcium enhances cadmium tolerance and decreases cadmium ...

African Journals Online (AJOL)

We aimed at characterizing mechanisms controlling cadmium accumulation in lettuce, which is a food crop showing one of the highest capacities to accumulate this toxic compound. In this study, plants from three lettuce varieties were grown for eight days on media supplemented or not with cadmium (15 μM CdCl2) and ...

Comprehensive characterization of glutamine synthetase-mediated selection for the establishment of recombinant CHO cells producing monoclonal antibodies

DEFF Research Database (Denmark)

Noh, Soo Min; Shin, Seunghyeon; Min Lee, Gyun

2018-01-01

To characterize a glutamine synthetase (GS)-based selection system, monoclonal antibody (mAb) producing recombinant CHO cell clones were generated by a single round of selection at various methionine sulfoximine (MSX) concentrations (0, 25, and 50 μM) using two different host cell lines (CHO-K1...... and GS-knockout CHO). Regardless of the host cell lines used, the clones selected at 50 μM MSX had the lowest average specific growth rate and the highest average specific production rates of toxic metabolic wastes, lactate and ammonia. Unlike CHO-K1, high producing clones could be generated...... in the absence of MSX using GS-knockout CHO with an improved selection stringency. Regardless of the host cell lines used, the clones selected at various MSX concentrations showed no significant difference in the GS, heavy chain, and light chain gene copies (P > 0.05). Furthermore, there was no correlation...

A Naturally Occurring Domestic Cat APOBEC3 Variant Confers Resistance to Feline Immunodeficiency Virus Infection.

Science.gov (United States)

Yoshikawa, Rokusuke; Izumi, Taisuke; Yamada, Eri; Nakano, Yusuke; Misawa, Naoko; Ren, Fengrong; Carpenter, Michael A; Ikeda, Terumasa; Münk, Carsten; Harris, Reuben S; Miyazawa, Takayuki; Koyanagi, Yoshio; Sato, Kei

2016-01-01

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) DNA cytosine deaminases can be incorporated into progeny virions and inhibit lentiviral replication. On the other hand, viral infectivity factor (Vif) of lentiviruses antagonizes A3-mediated antiviral activities by degrading A3 proteins. It is known that domestic cat (Felis catus) APOBEC3Z3 (A3Z3), the ortholog of human APOBEC3H, potently suppresses the infectivity of vif-defective feline immunodeficiency virus (FIV). Although a recent report has shown that domestic cat encodes 7 haplotypes (hap I to hap VII) of A3Z3, the relevance of A3Z3 polymorphism in domestic cats with FIV Vif has not yet been addressed. In this study, we demonstrated that these feline A3Z3 variants suppress vif-defective FIV infectivity. We also revealed that codon 65 of feline A3Z3 is a positively selected site and that A3Z3 hap V is subject to positive selection during evolution. It is particularly noteworthy that feline A3Z3 hap V is resistant to FIV Vif-mediated degradation and still inhibits vif-proficient viral infection. Moreover, the side chain size, but not the hydrophobicity, of the amino acid at position 65 determines the resistance to FIV Vif-mediated degradation. Furthermore, phylogenetic analyses have led to the inference that feline A3Z3 hap V emerged approximately 60,000 years ago. Taken together, these findings suggest that feline A3Z3 hap V may have been selected for escape from an ancestral FIV. This is the first evidence for an evolutionary "arms race" between the domestic cat and its cognate lentivirus. Gene diversity and selective pressure are intriguing topics in the field of evolutionary biology. A direct interaction between a cellular protein and a viral protein can precipitate an evolutionary arms race between host and virus. One example is primate APOBEC3G, which potently restricts the replication of primate lentiviruses (e.g., human immunodeficiency virus type 1 [HIV-1] and simian

Production of high purity granular metals: cadmium, zinc, lead

Directory of Open Access Journals (Sweden)

Shcherban A. P.

2017-04-01

Full Text Available Cadmium, zinc and lead are constituent components of many semiconductor compounds. The obtained high purity distillates and ingots are large-size elements, which is not always convenient to use, and thus require additional grinding, which does not always allow maintaining the purity of the original materials. For the growth of semiconductor and scintillation single crystals it is advisable to use "friable" granular high-purity distillates, which can be processed without the risk of contamination. For example, the European low-background experiment LUCIFER required more than 20 kg of high-purity granulated zinc, which was agreed to be supplied by NSC KIPT. This task was then extended to cadmium and lead. Motivated by these tasks, the authors of this paper propose complex processes of deep refining of cadmium, zinc and lead by vacuum distillation. A device producing granules has been developed. The process of granulation of high-purity metals is explored. The purity of produced granules for cadmium and zinc is >99,9999, and >99,9995% for lead granules. To prevent oxidation of metal granules during exposition to air, chemical methods of surface passivation were used. Organic solvent based on dimethylformamide used as a coolant improves the resistance of granules to atmospheric corrosion during the granulation of high purity Cd, Zn and Pb.

Interaction between lactose and cadmium chloride in aqueous solutions as seen by diffusion coefficients measurements

International Nuclear Information System (INIS)

Verissimo, Luis M.P.; Gomes, Joselaine C.S.; Romero, Carmen; Esteso, Miguel A.; Sobral, Abilio J.F.N.; Ribeiro, Ana C.F.

2013-01-01

Highlights: ► Diffusion coefficients of aqueous systems containing lactose and cadmium chloride. ► Influence of the lactose on the diffusion of cadmium chloride. ► Interactions between Cd 2+ and lactose. -- Abstract: Diffusion coefficients of an aqueous system containing cadmium chloride 0.100 mol · dm −3 and lactose at different concentrations at 25 °C have been measured, using a conductimetric cell and an automatic apparatus to follow diffusion. The cell relies on an open-ended capillary method and a conductimetric technique is used to follow the diffusion process by measuring the resistance of a solution inside the capillaries, at recorded times. From these results and by ab initio calculations, it was possible to obtain a better understanding of the effect of lactose on transport of cadmium chloride in aqueous solutions

Supplementation of Nucleosides During Selection can Reduce Sequence Variant Levels in CHO Cells Using GS/MSX Selection System.

Science.gov (United States)

Tang, Danming; Lam, Cynthia; Louie, Salina; Hoi, Kam Hon; Shaw, David; Yim, Mandy; Snedecor, Brad; Misaghi, Shahram

2018-01-01

In the process of generating stable monoclonal antibody (mAb) producing cell lines, reagents such as methotrexate (MTX) or methionine sulfoximine (MSX) are often used. However, using such selection reagent(s) increases the possibility of having higher occurrence of sequence variants in the expressed antibody molecules due to the effects of MTX or MSX on de novo nucleotide synthesis. Since MSX inhibits glutamine synthase (GS) and results in both amino acid and nucleoside starvation, it is questioned whether supplementing nucleosides into the media could lower sequence variant levels without affecting titer. The results show that the supplementation of nucleosides to the media during MSX selection decreased genomic DNA mutagenesis rates in the selected cells, probably by reducing nucleotide mis-incorporation into the DNA. Furthermore, addition of nucleosides enhance clone recovery post selection and does not affect antibody expression. It is further observed that nucleoside supplements lowered DNA mutagenesis rates only at the initial stage of the clone selection and do not have any effect on DNA mutagenesis rates after stable cell lines are established. Therefore, the data suggests that addition of nucleosides during early stages of MSX selection can lower sequence variant levels without affecting titer or clone stability in antibody expression. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Targeted transgene insertion into the CHO cell genome using Cre recombinase-incorporating integrase-defective retroviral vectors.

Science.gov (United States)

Kawabe, Yoshinori; Shimomura, Takuya; Huang, Shuohao; Imanishi, Suguru; Ito, Akira; Kamihira, Masamichi

2016-07-01

Retroviral vectors have served as efficient gene delivery tools in various biotechnology fields. However, viral DNA is randomly inserted into the genome, which can cause problems, such as insertional mutagenesis and gene silencing. Previously, we reported a site-specific gene integration system, in which a transgene is integrated into a predetermined chromosomal locus of Chinese hamster ovary (CHO) cells using integrase-defective retroviral vectors (IDRVs) and Cre recombinase. In this system, a Cre expression plasmid is transfected into founder cells before retroviral transduction. In practical applications of site-specific gene modification such as for hard-to-transfect cells or for in vivo gene delivery, both the transgene and the Cre protein into retroviral virions should be encapsulate. Here, we generated novel hybrid IDRVs in which viral genome and enzymatically active Cre can be delivered (Cre-IDRVs). Cre-IDRVs encoding marker genes, neomycin resistance and enhanced green fluorescent protein (EGFP), flanked by wild-type and mutated loxP sites were produced using an expression plasmid for a chimeric protein of Cre and retroviral gag-pol. After analyzing the incorporation of the Cre protein into retroviral virions by Western blotting, the Cre-IDRV was infected into founder CHO cells, in which marker genes (hygromycin resistance and red fluorescent protein) flanked with corresponding loxP sites are introduced into the genome. G418-resistant colonies expressing GFP appeared and the site-specific integration of the transgene into the expected chromosomal site was confirmed by PCR and sequencing of amplicons. Moreover, when Cre-IDRV carried a gene expression unit for a recombinant antibody, the recombinant cells in which the antibody expression cassette was integrated in a site-specific manner were generated and the cells produced the recombinant antibody. This method may provide a promising tool to perform site-specific gene modification according to Cre

Effects of cadmium electrode properties on nickel-cadmium cell performance

International Nuclear Information System (INIS)

Zimmerman, A.H.

1986-01-01

Tests have been conducted on a number of nickel-cadmium cells that have exhibited a variety of performance problems, ranging from high voltages and pressures during overcharge to low capacity. The performance problems that have been specifically linked to the cadmium electrode are primarily related to two areas, poor sinter and the buildup of excessive pressure during overcharge. A number of specific nickel-cadmium cell and cadmium electrode characterists have been studied in this work to determine what the effects of poor sinter are, and to determine what factors are important in causing excessive pressures during overcharge in cells that otherwise appear normal. Several of the tests appear suitable for screening cells and electrodes for such problems

HCV Drug Resistance Challenges in Japan: The Role of Pre-Existing Variants and Emerging Resistant Strains in Direct Acting Antiviral Therapy

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Kazuaki Chayama

2015-10-01

Full Text Available Sustained virological response (SVR rates have increased dramatically following the approval of direct acting antiviral (DAA therapies. While individual DAAs have a low barrier to resistance, most patients can be successfully treated using DAA combination therapy. However, DAAs are vulnerable to drug resistance, and resistance-associated variants (RAVs may occur naturally prior to DAA therapy or may emerge following drug exposure. While most RAVs are quickly lost in the absence of DAAs, compensatory mutations may reinforce fitness. However, the presence of RAVs does not necessarily preclude successful treatment. Although developments in hepatitis C virus (HCV therapy in Asia have largely paralleled those in the United States, Japan’s July 2014 approval of asunaprevir plus daclatasvir combination therapy as the first all-oral interferon-free therapy was not repeated in the United States. Instead, two different combination therapies were approved: sofosbuvir/ledipasvir and paritaprevir/ritonavir/ombitasvir/dasabuvir. This divergence in treatment approaches may lead to differences in resistance challenges faced by Japan and the US. However, the recent approval of sofosbuvir plus ledipasvir in Japan and the recent submissions of petitions for approval of paritaprevir/ritonavir plus ombitasvir suggest a trend towards a new consensus on emerging DAA regimens.

Perforate on CHO cell membranes induced by electromagnetic ...

African Journals Online (AJOL)

STORAGESEVER

2009-06-17

Jun 17, 2009 ... Key words: Electromagnetic pulse (EMP), atomic force microscope, CHO cell, cell membrane. INTRODUCTION .... of perforation ranges from 390 to 660 nm and the depth is. 392.95 nm. ... cell membrane perforations increased when both the field intensity and ..... Melatonin and a spin-trap compound block.

11C-CHO PET in optimization of target volume delineation and treatment regimens in postoperative radiotherapy for brain gliomas

International Nuclear Information System (INIS)

Li Fangming; Nie Qing; Wang Ruimin; Chang, Susan M.; Zhao Wenrui; Zhu Qi; Liang Yingkui; Yang Ping; Zhang Jun; Jia Haiwei; Fang Henghu

2012-01-01

Objective: We explored the clinical values of 11 C-choline ( 11 C-CHO) PET in optimization of target volume delineation and treatment regimens in postoperative radiotherapy for brain gliomas. Methods: Sixteen patients with the pathological confirmation of the diagnosis of gliomas prior to receiving radiotherapy (postoperative) were included, and on whom both MRI and CHO PET scans were performed at the same position for comparison of residual tumors with the two techniques. 11 C-CHO was used as the tracer in the PET scan. A plain T1-weighted, T2-weighted and contrast-enhanced T1-weighted imaging scans were performed in the MRI scan sequence. The gliomas' residual tumor volume was defined as the area with CHO-PET high-affinity uptake and metabolism (V CHO ) and one with MRI T1-weighted imaging high signal intensity (V Gd ), and was determined by a group of experienced professionals and clinicians. Results: (1) In CHO-PET images, the tumor target volume, i.e., the highly metabolic area with a high concentration of isotopes (SUV 1.016–4.21) and the corresponding contralateral normal brain tissues (SUV0.1–0.62), was well contrasted, and the boundary between lesions and surrounding normal brain tissues was better defined compared with MRI and 18 F-FDG PET images. (2) For patients with brain gliomas of WHO Grade II, the SUV was 1.016–2.5; for those with WHO Grades III and IV, SUVs were >26–4.2. (3) Both CHO PET and MRI were positive for 10 patients and negative for 2 patients. The residual tumor consistency between these two studies was 75%. Four of the 10 CHO-PET-positive patients were negative on MRI scans. The maximum distance between V Gd and V CHO margins was 1.8 cm. (4) The gross tumor volumes (GTVs) and the ensuing treatment regimens were changed for 31.3% (5/16) of patients based on the CHO-PET high-affinity uptake and metabolism, in which the change rate was 80% (4/5), 14.3 % (1/7) and 0% (0/4) for patients with WHO Grade II III, and IV gliomas

Molecular basis of cadmium toxicity

Energy Technology Data Exchange (ETDEWEB)

Nath, R; Prasad, R; Palinal, V K; Chopra, R K

1984-01-01

Cadmium has been shown to manifest its toxicity in human and animals by mainly accumulating in almost all of the organs. The kidney is the main target organ where it is concentrated mainly in the cortex. Environmental exposure of cadmium occurs via food, occupational industries, terrestrial and aquatic ecosystem. At molecular level, cadmium interferes with the utilization of essential metals e.g. Ca, Zn, Se, Cr and Fe and deficiencies of these essential metals including protein and vitamins, exaggerate cadmium toxicity, due to its increased absorption through the gut and greater retention in different organs as metallothionein (Cd-Mt). Cadmium transport, across the intestinal and renal brush border membrane vesicles, is carrier mediated and it competes with zinc and calcium. It has been postulated that cadmium shares the same transport system. Cadmium inhibits protein synthesis, carbohydrate metabolism and drug metabolizing enzymes in liver of animals. Chronic environmental exposure of cadmium produces hypertension in experimental animals. Functional changes accompanying cadmium nephropathy include low molecular weight proteinuria which is of tubular origin associated with excess excretion of proteins such as beta 2 microglobulin, metallothionein and high molecular weight proteinuria of glomerular origin (excretion of proteins such as albumin IgG, transferrin etc.). Recent data has shown that metallothionein is more nephrotoxic to animals. Cadmium is also toxic to central nervous system. It causes an alterations of cellular functions in lungs. Cadmium affects both humoral and cell mediated immune response in animals. Cadmium induces metallothionein in liver and kidney but under certain nutritional deficiencies like protein-calorie malnutrition and calcium deficiency, enhanced induction and greater accumulation of cadmium metallothionein has been observed.

Cross-cultural adaptation of the CHO-KLAT for boys with hemophilia in rural and urban china

Directory of Open Access Journals (Sweden)

Wu Runhui

2012-09-01

Full Text Available Abstract Background Quality of life (QoL is increasingly recognized as an important outcome measure in clinical trials. The Canadian Hemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT shows promise for use in China. Objective To adapt the CHO-KLAT version 2.0 for use in clinical trials in China. Methods Forward and back translations of the CHO-KLAT2.0 were completed in 2008. Between October 2009 and June 2010, a series of 3 focus groups were held with 20 boys and 31 parents in rural and urban China to elicit additional concepts, important to their QoL, for the Chinese CHO-KLAT2.0. All of the items identified by boys and parents were reviewed by a group of experts, resulting in a Chinese version of the CHO-KLAT2.0. This version underwent a detailed cognitive debriefing process between October 2010 and June 2011. Thirteen patient-parent pairs participated in this cognitive debriefing process until a stable and clearly understood Chinese version of the CHO-KLAT2.0 was obtained. Results The initial back translation of the Chinese CHO-KLAT2.0 was slightly discrepant from the original English version on 12 items. These were all successfully adjudicated. The focus groups identified 9 new items that formed an add-on Socio-Economic Context (SEC module for China. Linguistic improvements were made after the 2nd, 5th, 7th and 13th cognitive debriefings pairs and affected a total of 18 items. The result was a 35 item CHO-KLAT2.0 and a SEC module in Simplified Chinese, both of which have good content validity. Conclusion This detailed process proved to be extremely valuable in ensuring the items were accurately interpreted by Chinese boys with hemophilia ages ≤18 years. The need for the additional SEC module highlighted the different context that currently exists in China with regard to hemophilia care as compared to many Western countries, and will be important in tracking progress within both rural and urban China over time. Changes based on the

miR-2861 as novel HDAC5 inhibitor in CHO cells enhances productivity while maintaining product quality.

Science.gov (United States)

Fischer, Simon; Paul, Albert Jesuran; Wagner, Andreas; Mathias, Sven; Geiss, Melanie; Schandock, Franziska; Domnowski, Martin; Zimmermann, Jörg; Handrick, René; Hesse, Friedemann; Otte, Kerstin

2015-10-01

Histone deacetylase (HDAC) inhibitors have been exploited for years to improve recombinant protein expression in mammalian production cells. However, global HDAC inhibition is associated with negative effects on various cellular processes. microRNAs (miRNAs) have been shown to regulate gene expression in almost all eukaryotic cell types by controlling entire cellular pathways. Since miRNAs recently have gained much attention as next-generation cell engineering tool to improve Chinese hamster ovary (CHO) cell factories, we were interested if miRNAs are able to specifically repress HDAC expression in CHO cells to circumvent limitations of unspecific HDAC inhibition. We discovered a novel miRNA in CHO cells, miR-2861, which was shown to enhance productivity in various recombinant CHO cell lines. Furthermore, we demonstrate that miR-2861 might post-transcriptionally regulate HDAC5 in CHO cells. Intriguingly, siRNA-mediated HDAC5 suppression could be demonstrated to phenocopy pro-productive effects of miR-2861 in CHO cells. This supports the notion that miRNA-induced inhibition of HDAC5 may contribute to productivity enhancing effects of miR-2861. Furthermore, since product quality is fundamental to safety and functionality of biologics, we examined the effect of HDAC inhibition on critical product quality attributes. In contrast to unspecific HDAC inhibition using VPA, enforced expression of miR-2861 did not negatively influence antibody aggregation or N-glycosylation. Our findings highlight the superiority of miRNA-mediated inhibition of specific HDACs and present miR-2861 as novel cell engineering tool for improving CHO manufacturing cells. © 2015 Wiley Periodicals, Inc.

Effects of inoculation of biosurfactant-producing Bacillus sp. J119 on plant growth and cadmium uptake in a cadmium-amended soil

International Nuclear Information System (INIS)

Sheng Xiafang; He Linyan; Wang Qingya; Ye Hesong; Jiang Chunyu

2008-01-01

A biosurfactant-producing Bacillus sp. J119 isolated from heavy metal contaminated soils was investigated for its effects on the plant growth-promoting characteristics and heavy metal and antibiotic resistance. A pot experiment was conducted for investigating the capability of the biosurfactant-producing bacterial strain Bacillus sp. J119 to promote the plant growth and cadmium uptake of rape, maize, sudangrass and tomato in soil artificially contaminated with different levels of cadmium (Cd) (0 and 50 mg kg -1 ). The strain was found to exhibit different multiple heavy metal (Pb, Cd, Cu, Ni and Zn) and antibiotic (kanamycin, streptomycin, ampicillin, tetracycline and rifampin) resistance characteristics. The strain had the capacity to produce indole acetic acid (IAA) and siderophores. Cd treatment did not significantly decreased growth of tomato, maize and rape plants, but Cd treatment significantly decreased growth of sudangrass (p -1 , increase in above-ground tissue Cd content varied from 39 to 70% in live bacterium-inoculated plants compared to dead bacterium-inoculated control. In addition, among the inoculated plants, tomato was the greatest Cd accumulator. The bacterial strain was also able to colonize and develop in the rhizosphere soils after root inoculation

Cadmium-containing waste and recycling possibilities

International Nuclear Information System (INIS)

Wiegand, V.; Rauhut, A.

1981-01-01

To begin with, the processes of cadmium production from zinc ores in smelting plants or from intermediates of other metal works are described. A considerable amount of the cadmium is obtained in the recycling process in zinc, lead, and copper works. The way of the cadmium-containing intermediaries, processing, enrichment, and disposal of cadmium waste are described. Uses of cadmium and its compounds are mentioned, and cadmium consumption in the years 1973-1977 in West Germany is presented in a table. Further chapters discuss the production and the way of waste during production and processing of cadmium-containing products, the problem of cadmium in household refuse and waste incineration plants, and the problem of cadmium emissions. (IHOE) [de

Multi-omic profiling of EPO-producing CHO cell panel reveals metabolic adaptation to heterologous protein production

DEFF Research Database (Denmark)

Ley, Daniel; Kazemi Seresht, Ali; Engmark, Mikael

The Chinese hamster ovary (CHO) cell line is the predominant mammalian cell factory for production of therapeutic glycoproteins. In this work, we aimed to study bottlenecks in the secretory pathway associated with the production of human erythropoietin (EPO) in CHO cells. In connection to this, we...... discovered indications of metabolic adaptation of the amino acid catabolism in favor of heterologous protein production. We established a panel of stably EPO expressing CHO-K1 clones spanning a 25-fold productivity range and characterized the clones in batch and chemostat cultures. For this, we employed...... a multi-omic physiological characterization including metabolic foot printing of amino acids, metabolite fingerprinting of glycolytic intermediates, NAD(P)H-/NAD(P)+ and adenosine nucleotide phosphates. We used qPCR, qRT-PCR, western blots and Affymetrix CHO microarrays to assess EPO gene copy numbers...

The prevalence of the pre-existing hepatitis C viral variants and the evolution of drug resistance in patients treated with the NS3-4a serine protease inhibitor telaprevir

Energy Technology Data Exchange (ETDEWEB)

Rong, Libin [Los Alamos National Laboratory; Ribeiro, Ruy M [Los Alamos National Laboratory; Perelson, Alan S [Los Alamos National Laboratory

2008-01-01

Telaprevir (VX-950), a novel hepatitis C virus (HCV) NS3-4A serine protease inhibitor, has demonstrated substantial antiviral activity in patients infected with HCV genotype 1. Some patients experience viral breakthrough, which has been shown to be associated with emergence of telaprevir-resistant HCV variants during treatment. The exact mechanisms underlying the rapid selection of drug resistant viral variants during dosing are not fully understood. In this paper, we develop a two-strain model to study the pre-treatment prevalence of the mutant virus and derive an analytical solution of the mutant frequency after administration of the protease inhibitor. Our analysis suggests that the rapid increase of the mutant frequency during therapy is not due to mutant growth but rather due to the rapid and profound loss of wild-type virus, which uncovers the pre-existing mutant variants. We examine the effects of backward mutation and hepatocyte proliferation on the pre-existence of the mutant virus and the competition between wild-type and drug resistant virus during therapy. We then extend the simple model to a general model with multiple viral strains. Mutations during therapy do not play a significant role in the dynamics of various viral strains, although they are capable of generating low levels of HCV variants that would otherwise be completely suppressed because of fitness disadvantages. Hepatocyte proliferation may not affect the pretreatment frequency of mutant variants, but is able to influence the quasispecies dynamics during therapy. It is the relative fitness of each mutant strain compared with wild-type that determines which strain(s) will dominate the virus population. The study provides a theoretical framework for exploring the prevalence of pre-existing mutant variants and the evolution of drug resistance during treatment with other protease inhibitors or HCV polymerase inhibitors.

Accelerated and Rational Design of Improved CHO Cell Factories

DEFF Research Database (Denmark)

Grav, Lise Marie

Recombinant production of therapeutic proteins provides huge benefits to human health and promises solutions to some of the most devastating and currently untreatable diseases in healthcare. Key to the development of new therapeutic proteins is to optimize and engineer living cells, namely cell...... of a number of novel tools is reported that aim to accelerate the construction of production cell lines for therapeutic proteins with optimal phenotypic attributes for industrial processes. Chinese hamster ovary (CHO) cells are the predominant production host for therapeutic proteins, and are the cell factory...... of interest in this thesis. The core of the thesis is revolved around the development and application of genome editing techniques that enable us to precisely engineer the genome of CHO cells by either rendering specific-targeted genes unfunctional or inserting new genes in precise genomic locations...

Bioreactor scale up and protein product quality characterization of piggyBac transposon derived CHO pools.

Science.gov (United States)

Rajendra, Yashas; Balasubramanian, Sowmya; Peery, Robert B; Swartling, James R; McCracken, Neil A; Norris, Dawn L; Frye, Christopher C; Barnard, Gavin C

2017-03-01

Chinese hamster ovary (CHO) cells remain the most popular host for the production of biopharmaceutical drugs, particularly monoclonal antibodies (mAbs), bispecific antibodies, and Fc-fusion proteins. Creating and characterizing the stable CHO clonally-derived cell lines (CDCLs) needed to manufacture these therapeutic proteins is a lengthy and laborious process. Therefore, CHO pools have increasingly been used to rapidly produce protein to support and enable preclinical drug development. We recently described the generation of CHO pools yielding mAb titers as high as 7.6 g/L in a 16 day bioprocess using piggyBac transposon-mediated gene integration. In this study, we wanted to understand why the piggyBac pool titers were significantly higher (2-10 fold) than the control CHO pools. Higher titers were the result of a combination of increased average gene copy number, significantly higher messenger RNA levels and the homogeneity (i.e. less diverse population distribution) of the piggyBac pools, relative to the control pools. In order to validate the use of piggyBac pools to support preclinical drug development, we then performed an in-depth product quality analysis of purified protein. The product quality of protein obtained from the piggyBac pools was very similar to the product quality profile of protein obtained from the control pools. Finally, we demonstrated the scalability of these pools from shake flasks to 36L bioreactors. Overall, these results suggest that gram quantities of therapeutic protein can be rapidly obtained from piggyBac CHO pools without significantly changing product quality attributes. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:534-540, 2017. © 2017 American Institute of Chemical Engineers.

Perforate on CHO cell membranes induced by electromagnetic ...

African Journals Online (AJOL)

Atomic force microscopy (AFM) has been used to visualize the morphological change on the surface of Chinese hamster ovary (CHO) cell membranes before and after electromagnetic pulses (EMP) irradiation. The results show that there were different sizes and shapes of membrane perforate (width ranging from 0.39 - 0.66 ...

Engineered CHO cells for production of diverse, homogeneous glycoproteins

DEFF Research Database (Denmark)

Yang, Zhang; Wang, Shengjun; Halim, Adnan

2015-01-01

Production of glycoprotein therapeutics in Chinese hamster ovary (CHO) cells is limited by the cells' generic capacity for N-glycosylation, and production of glycoproteins with desirable homogeneous glycoforms remains a challenge. We conducted a comprehensive knockout screen of glycosyltransferas...

The roles of variants in human multidrug resistance (MDR1 gene and their haplotypes on antiepileptic drugs response: a meta-analysis of 57 studies.

Directory of Open Access Journals (Sweden)

Hui Li

Full Text Available Previous studies reported the associations between the ATP-binding cassette sub-family B member 1 (ABCB1, also known as MDR1 polymorphisms and their haplotypes with risk of response to antiepileptic drugs in epilepsy, however, the results were inconclusive.The Pubmed, Embase, Web of Science, CNKI and Chinese Biomedicine databases were searched up to July 15, 2014. Pooled odds ratios (ORs and 95% confidence intervals (CIs were calculated using a fixed-effects or random-effects model based on heterogeneity tests. Meta-regression and Galbraith plot analysis were carried out to explore the possible heterogeneity.A total of 57 studies involving 12407 patients (6083 drug-resistant and 6324 drug-responsive patients with epilepsy were included in the pooled-analysis. For all three polymorphisms (C3435T, G2677T/A, and C1236T, we observed a wide spectrum of minor allele frequencies across different ethnicities. A significantly decreased risk of AEDs resistance was observed in Caucasian patients with T allele of C3435T variant, which was still significant after adjusted by multiple testing corrections (T vs C: OR=0.83, 95%CI=0.71-0.96, p=0.01. However, no significant association was observed between the other two variants and AEDs resistance. Of their haplotypes in ABCB1 gene (all studies were in Indians and Asians, no significant association was observed with AEDs resistance. Moreover, sensitivity and Cumulative analysis showed that the results of this meta-analysis were stable.In summary, this meta-analysis demonstrated that effect of C3435T variant on risk of AEDs resistance was ethnicity-dependent, which was significant in Caucasians. Additionally, further studies in different ethnic groups are warranted to clarify possible roles of haplotypes in ABCB1 gene in AEDs resistance, especially in Caucasians.

Nrf2 activation prevents cadmium-induced acute liver injury

International Nuclear Information System (INIS)

Wu, Kai C.; Liu, Jie J.; Klaassen, Curtis D.

2012-01-01

resistant to cadmium-induced liver injury. ► Cadmium increased ROS in hepatocytes isolated from Nrf2-null and wild-type mice. ► Mt-1 and Mt‐2 were induced over 200-fold in both Nrf2-null and Nrf2-enhanced mice. ► Gclc, Gpx2, and Srxn-1 were induced in Nrf2-enhanced mice, not in Nrf2-null mice.

Nrf2 activation prevents cadmium-induced acute liver injury

Energy Technology Data Exchange (ETDEWEB)

Wu, Kai C. [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Liu, Jie J. [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Klaassen, Curtis D., E-mail: cklaasse@kumc.edu [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States)

2012-08-15

were resistant to cadmium-induced liver injury. ► Cadmium increased ROS in hepatocytes isolated from Nrf2-null and wild-type mice. ► Mt-1 and Mt‐2 were induced over 200-fold in both Nrf2-null and Nrf2-enhanced mice. ► Gclc, Gpx2, and Srxn-1 were induced in Nrf2-enhanced mice, not in Nrf2-null mice.

Methods for modeling chinese hamster ovary (cho) cell metabolism

DEFF Research Database (Denmark)

2015-01-01

Embodiments of the present invention generally relate to the computational analysis and characterization biological networks at the cellular level in Chinese Hamster Ovary (CHO) cells. Based on computational methods utilizing a hamster reference genome, the invention provides methods for identify...

Cadmium in Sweden - environmental risks

Energy Technology Data Exchange (ETDEWEB)

Parkman, H; Iverfeldt, Aa [Swedish Environmental Research Inst. (Sweden); Borg, H; Lithner, G [Stockholm Univ. (Sweden). Inst. for Applied Environmental Research

1998-03-01

This report aims at assessing possible effects of cadmium in the Swedish environment. Swedish soils and soft freshwater systems are, due to a generally poor buffering capacity, severely affected by acidification. In addition, the low salinity in the Baltic Sea imply a naturally poor organism structure, with some important organisms living close to their limit of physiological tolerance. Cadmium in soils is mobilized at low pH, and the availability and toxicity of cadmium in marine systems are enhanced at low salinity. The Swedish environment is therefore extra vulnerable to cadmium pollution. The average concentrations of cadmium in the forest mor layers, agricultural soils, and fresh-waters in Sweden are enhanced compared to `back-ground concentrations`, with a general increasing trend from the north to the south-west, indicating strong impact of atmospheric deposition of cadmium originating from the central parts of Europe. In Swedish sea water, total cadmium concentrations, and the fraction of bio-available `free` cadmium, generally increases with decreasing salinity. Decreased emissions of cadmium to the environment have led to decreasing atmospheric deposition during the last decade. The net accumulation of cadmium in the forest mor layer has stopped, and even started to decrease. In northern Sweden, this is due to the decreased deposition, but in southern Sweden the main reason is increased leakage of cadmium from the topsoil as a consequence of acidification. As a result, cadmium in the Swedish environments is undergoing an extended redistribution between different soil compartments, and from the soils to the aquatic systems. 90 refs, 23 figs, 2 tabs. With 3 page summary in Swedish

Determination of cadmium selenide nonstoichiometry

International Nuclear Information System (INIS)

Brezhnev, V.Yu.; Kharif, Ya.L.; Kovtunenko, P.V.

1986-01-01

Physicochemical method of determination of cadmium selenide nonstoichiometry is developed. The method nature consists in the fact, that under definite conditions dissolved cadmium is extracted from crystals to a vapor phase and then is determined in it using the photocolorimetric method. Cadmium solubility in CdSe crystal is calculated from known CdSe mass and amount of separated cadmium. The lower boundary of determined contents constitutes 1x10 -5 % mol at sample of cadmium selenide 10 g

Comprehensive characterization of glutamine synthetase-mediated selection for the establishment of recombinant CHO cells producing monoclonal antibodies.

Science.gov (United States)

Noh, Soo Min; Shin, Seunghyeon; Lee, Gyun Min

2018-03-29

To characterize a glutamine synthetase (GS)-based selection system, monoclonal antibody (mAb) producing recombinant CHO cell clones were generated by a single round of selection at various methionine sulfoximine (MSX) concentrations (0, 25, and 50 μM) using two different host cell lines (CHO-K1 and GS-knockout CHO). Regardless of the host cell lines used, the clones selected at 50 μM MSX had the lowest average specific growth rate and the highest average specific production rates of toxic metabolic wastes, lactate and ammonia. Unlike CHO-K1, high producing clones could be generated in the absence of MSX using GS-knockout CHO with an improved selection stringency. Regardless of the host cell lines used, the clones selected at various MSX concentrations showed no significant difference in the GS, heavy chain, and light chain gene copies (P > 0.05). Furthermore, there was no correlation between the specific mAb productivity and these three gene copies (R 2  ≤ 0.012). Taken together, GS-mediated gene amplification does not occur in a single round of selection at a MSX concentration up to 50 μM. The use of the GS-knockout CHO host cell line facilitates the rapid generation of high producing clones with reduced production of lactate and ammonia in the absence of MSX.

Enhancement of cadmium bioremediation by endophytic bacterium Bacillus sp. L14 using industrially used metabolic inhibitors (DCC or DNP)

International Nuclear Information System (INIS)

Luo Shenglian; Xiao Xiao; Xi Qiang; Wan Yong; Chen Liang; Zeng Guangming; Liu Chengbin; Guo Hanjun; Chen Jueliang

2011-01-01

Bioremediations of cadmium by endophytic bacterium (EB) L14 (Bacillus sp.) in the presence of industrially used metabolic inhibitors (DCC or DNP) were investigated. In the presence of DCC or DNP, the biomass population of EB L14 was greatly inhibited. However, the cadmium removal of EB L14 increased from 73.6% (in the absence of DCC or DNP) to 93.7% and 80.8%, respectively. The analysis of total and intracellular cadmium concentrations during 24 h of incubation indicated that this enhanced cadmium removal was the inhibition effect of DCC or DNP on the cations export resistance system of EB L14. This unique property strongly indicated the superiority of this endophyte for practical application in cadmium bioremediation in the presence of industrially used metabolic inhibitors.

Effect of dietary carbohydrate on non-specific immune response, hepatic antioxidative abilities and disease resistance of juvenile golden pompano (Trachinotus ovatus).

Science.gov (United States)

Zhou, Chuanpeng; Ge, Xianping; Lin, Heizhao; Niu, Jin

2014-12-01

The present study was conducted to investigate the effects of dietary carbohydrate (CHO) levels on non-specific immune responses, hepatic antioxidative status and disease resistance of juvenile golden pompano. Fish were fed six isonitrogenous and isoenergetic diets containing various CHO levels for 8 weeks. After the feeding trial, fish were challenged by Vibrio harveyi and survival rate was recorded for the next 12 days. Plasma total protein and albumin content, respiratory burst activity, alkaline phosphatase, slightly increased with dietary starch level from 0% to 16.8%, but significantly decreased at dietary starch levels of 16.8%-28%. Plasma lysozyme, complement 3 and complement 4 levels increased with increasing dietary carbohydrate up to 11.2% and then declined (P 0.05) with those of the other treatments. After challenge, fish fed 11.2% and 16.8% dietary CHO showed higher survival rate than that of fish in 0% CHO group (P 0.05). The results of this study suggest that ingestion of 11.2-16.8% dietary CHO can enhance the non-specific immune responses, increase the hepatic antioxidant abilities, and improve resistance to V. harveyi infection of juvenile golden pompano. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of the cadmium ion source on the structural and optical properties of chemical bath deposited CdS thin films

Energy Technology Data Exchange (ETDEWEB)

Rami, M.; Benamar, E.; Fahoume, M.; Chraibi, F.; Ennaoui, A. [University Mohamed V, Laboratory of Materials Physics, Dept., Faculty of Sciences, Rabat (Morocco)

1999-06-01

The chemical bath deposition (CBD) technique has been successfully used to deposit cadmium sulphide from cadmium chloride and cadmium acetate as the cadmium ion source and thiourea as the sulphur source on both glass microscope slide and indium tin oxide coated glass substrates. Various properties of the films such as surface morphology, crystallinity, optical properties and resistivity have been investigated. XRD patterns reveal that the CdS films deposited from cadmium chloride have an hexagonal structure. Their preferential orientation changes from (002) to (100) with the thermal annealing. Films deposited from cadmium acetate are amorphous but improve their crystallinity with annealing. SEM analysis shows that the grains of the as deposited films are randomly shaped and appear to be bigger in the case of the CdS prepared from cadmium chloride. The optical transmission of the layers are in the 70-80% range for wavelength above the band gap absorption which makes them more appropriate as window material in heterojunction solar cells. (authors)

GRL-09510, a Unique P2-Crown-Tetrahydrofuranylurethane -Containing HIV-1 Protease Inhibitor, Maintains Its Favorable Antiviral Activity against Highly-Drug-Resistant HIV-1 Variants in vitro

Energy Technology Data Exchange (ETDEWEB)

Amano, Masayuki; Miguel Salcedo-Gómez, Pedro; Yedidi, Ravikiran S.; Delino, Nicole S.; Nakata, Hirotomo; Venkateswara Rao, Kalapala; Ghosh, Arun K.; Mitsuya, Hiroaki

2017-09-25

We report that GRL-09510, a novel HIV-1 protease inhibitor (PI) containing a newly-generated P2-crown-tetrahydrofuranylurethane (Crwn-THF), a P2'-methoxybenzene, and a sulfonamide isostere, is highly active against laboratory and primary clinical HIV-1 isolates (EC50: 0.0014–0.0028 μM) with minimal cytotoxicity (CC50: 39.0 μM). Similarly, GRL-09510 efficiently blocked the replication of HIV-1NL4-3 variants, which were capable of propagating at high-concentrations of atazanavir, lopinavir, and amprenavir (APV). GRL-09510 was also potent against multi-drug-resistant clinical HIV-1 variants and HIV-2ROD. Under the selection condition, where HIV-1NL4-3 rapidly acquired significant resistance to APV, an integrase inhibitor raltegravir, and a GRL-09510 congener (GRL-09610), no variants highly resistant against GRL-09510 emerged over long-term in vitro passage of the virus. Crystallographic analysis demonstrated that the Crwn-THF moiety of GRL-09510 forms strong hydrogen-bond-interactions with HIV-1 protease (PR) active-site amino acids and is bulkier with a larger contact surface, making greater van der Waals contacts with PR than the bis-THF moiety of darunavir. The present data demonstrate that GRL-09510 has favorable features for treating patients infected with wild-type and/or multi-drug-resistant HIV-1 variants, that the newly generated P2-Crwn-THF moiety confers highly desirable anti-HIV-1 potency. The use of the novel Crwn-THF moiety sheds lights in the design of novel PIs.

Relation between dietary cadmium intake and biomarkers of cadmium exposure in premenopausal women accounting for body iron stores

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Julin Bettina

2011-12-01

Full Text Available Abstract Background Cadmium is a widespread environmental pollutant with adverse effects on kidneys and bone, but with insufficiently elucidated public health consequences such as risk of end-stage renal diseases, fractures and cancer. Urinary cadmium is considered a valid biomarker of lifetime kidney accumulation from overall cadmium exposure and thus used in the assessment of cadmium-induced health effects. We aimed to assess the relationship between dietary cadmium intake assessed by analyses of duplicate food portions and cadmium concentrations in urine and blood, taking the toxicokinetics of cadmium into consideration. Methods In a sample of 57 non-smoking Swedish women aged 20-50 years, we assessed Pearson's correlation coefficients between: 1 Dietary intake of cadmium assessed by analyses of cadmium in duplicate food portions collected during four consecutive days and cadmium concentrations in urine, 2 Partial correlations between the duplicate food portions and urinary and blood cadmium concentrations, respectively, and 3 Model-predicted urinary cadmium concentration predicted from the dietary intake using a one-compartment toxicokinetic model (with individual data on age, weight and gastrointestinal cadmium absorption and urinary cadmium concentration. Results The mean concentration of cadmium in urine was 0.18 (+/- s.d.0.12 μg/g creatinine and the model-predicted urinary cadmium concentration was 0.19 (+/- s.d.0.15 μg/g creatinine. The partial Pearson correlations between analyzed dietary cadmium intake and urinary cadmium or blood concentrations were r = 0.43 and 0.42, respectively. The correlation between diet and urinary cadmium increased to r = 0.54 when using a one-compartment model with individual gastrointestinal cadmium absorption coefficients based on the women's iron status. Conclusions Our results indicate that measured dietary cadmium intake can reasonably well predict biomarkers of both long-term kidney accumulation

[Investigation of urinary cadmium characteristics of the general population in three non-cadmium-polluted rural areas in China].

Science.gov (United States)

Han, Jingxiu; Hu, Ji; Sun, Hong; Jing, Qiqing; Wang, Xiaofeng; Lou, Xiaoming; Ding, Zhen; Chen, Xiaodong; Zhang, Wenli; Shang, Qi

2014-11-01

To investigate the characteristics of urinary cadmium of the non-occupational-cadmium-exposed population in non-cadmium contaminated rural area in China. Randomly selected non-occupational cadmium exposed population 2548 people (male 1290, female 1258) with each gender and age groups, questionnaire surveyed and collected random urine. Urinary cadmium and urinary creatinine (Cr) concentration were tested, excluding urinary Cr 3 g/L. Analyze the impact factors of urinary cadmium and calculated 95% quantile (P95) of urinary cadmium after correction by urinary Cr. Urinary cadmium increased with age and showed an upward trend. The urinary cadmium of the population of ≥ 30 years old was significantly higher than that of populations (China (GB Z17-2002). The urinary cadmium reference value of non-occupational-cadmium-exposed populations is China, but for smoking women over 30 year-old it needs more research to explore.

Improving the efficiency of CHO cell line generation using glutamine synthetase gene knockout cells.

Science.gov (United States)

Fan, Lianchun; Kadura, Ibrahim; Krebs, Lara E; Hatfield, Christopher C; Shaw, Margaret M; Frye, Christopher C

2012-04-01

Although Chinese hamster ovary (CHO) cells, with their unique characteristics, have become a major workhorse for the manufacture of therapeutic recombinant proteins, one of the major challenges in CHO cell line generation (CLG) is how to efficiently identify those rare, high-producing clones among a large population of low- and non-productive clones. It is not unusual that several hundred individual clones need to be screened for the identification of a commercial clonal cell line with acceptable productivity and growth profile making the cell line appropriate for commercial application. This inefficiency makes the process of CLG both time consuming and laborious. Currently, there are two main CHO expression systems, dihydrofolate reductase (DHFR)-based methotrexate (MTX) selection and glutamine synthetase (GS)-based methionine sulfoximine (MSX) selection, that have been in wide industrial use. Since selection of recombinant cell lines in the GS-CHO system is based on the balance between the expression of the GS gene introduced by the expression plasmid and the addition of the GS inhibitor, L-MSX, the expression of GS from the endogenous GS gene in parental CHOK1SV cells will likely interfere with the selection process. To study endogenous GS expression's potential impact on selection efficiency, GS-knockout CHOK1SV cell lines were generated using the zinc finger nuclease (ZFN) technology designed to specifically target the endogenous CHO GS gene. The high efficiency (∼2%) of bi-allelic modification on the CHO GS gene supports the unique advantages of the ZFN technology, especially in CHO cells. GS enzyme function disruption was confirmed by the observation of glutamine-dependent growth of all GS-knockout cell lines. Full evaluation of the GS-knockout cell lines in a standard industrial cell culture process was performed. Bulk culture productivity improved two- to three-fold through the use of GS-knockout cells as parent cells. The selection stringency was

Collapsing variant of focal segmental glomerulosclerosis in children = Variante colapsante de la glomeruloesclerosis focal y segmentaria en niños

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Jonh Fredy Nieto Ríos

2013-10-01

Full Text Available Focal segmental glomerulosclerosis (FSGS collapsing variant refers to a renal lesion that may be idiopathic or associated to some factors, characterized by glomerular collapse leading to cortico-resistant nephrotic syndrome and chronic progressive renal failure. This glomerulopathy has been scarcely studied in children, but in this age group most cases are idiopathic. In this paper we present a report of 6 cases of collapsing variant of FSGS in children no associated to HIV, which were resistant to immunosuppressive management and with a high mortality

N-Glycosylation optimization of recombinant antibodies in CHO cell through process and metabolic engineering

DEFF Research Database (Denmark)

Fan, Yuzhou

, analysis, control and optimization of N-glycosylation were thoroughly reviewed. In particular, how to control and optimize N-glycosylation in CHO cells was exclusively studied. The main focus of this PhD project is to find effective approaches of modulating N-glycosylation of CHO-derived recombinant...... galactose as feed additives, changing process parameters such as seeding density and cultivation duration are all demonstrated to be effective. The causal explanation of their impact on glycosylation can be various, including product, metabolism, proteome and physiology-associated mechanism. In the middle...... part of the thesis, both literature reviews and experimental applications were provided to demonstrate how to use omics data and implement systems biology to understand biological activities, especially N-glycosylation in CHO cells. In the last part of the thesis, the second strategy that apply genetic...

Adriamycin resistance, heat resistance and radiation response in Chinese hamster fibroblasts

International Nuclear Information System (INIS)

Wallner, K.; Li, G.

1985-01-01

Previous investigators have demonstrated synergistic interaction between hyperthermia and radiation or Adriamycin (ADR), using cell lines that are sensitive to heat or ADR alone. The authors investigated the effect of heat, radiation or ADR on Chinese hamster fibroblasts (HA-1), their heat resistant variants and their ADR resistant variants. Heat for ADR resistance did not confer cross resistance to radiation. Cells resistant to heat did show cross resistance to ADR. While cells selected for ADR resistance were not cross resistant to heat, they did not exhibit drug potentiation by hyperthermia, characteristic of ADR sensitive cells. Cytofluorometric measurement showed decreased ADR uptake in both heat and ADR resistant cells. The possibility of cross resistance between heat and ADR should be considered when designing combined modality trials

Low fraction of the 222K PrP variant in the protease-resistant moiety of PrPres in heterozygous scrapie positive goats

OpenAIRE

Mazza, Maria; Guglielmetti, Chiara; Ingravalle, Francesco; Brusadore, Sonia; Langeveld, Jan P. M.; Ekateriniadou, Loukia V.; Andréoletti, Olivier; Casalone, Cristina; Acutis, Pier Luigi

2017-01-01

The presence of lysine (K) at codon 222 has been associated with resistance to classical scrapie in goats, but few scrapie cases have been identified in 222Q/K animals. To investigate the contribution of the 222K variant to PrPres formation in natural and experimental Q/K scrapie cases, we applied an immunoblotting method based on the use of two different monoclonal antibodies, F99/97.6.1 and SAF84, chosen for their different affinities to 222K and 222Q PrP variants. Our finding that PrPres s...

Cadmium induces Ca2+ mediated, calpain-1/caspase-3-dependent apoptosis in primary cultured rat proximal tubular cells.

Science.gov (United States)

Wang, Hong; Zhai, Nianhui; Chen, Ying; Xu, Haibin; Huang, Kehe

2017-07-01

Calcium, as a ubiquitous second messenger, governs a large array of cellular processes and is necessary for cell survival. More recently, it was observed that the cytosolic Ca 2+ concentration ([Ca 2+ ] c ) elevation could induce apoptosis in primary cultured rat proximal tubular (rPT) cells exposed to cadmium (Cd), but the concrete mechanism is still unclear. This study was designed to investigate the signal pathway involved in [Ca 2+ ] c elevation-mediated apoptosis. The results confirmed the elevation of [Ca 2+ ] c by confocal microscopy and enhancement of the apoptosis by Hoechst 33258 staining and flow cytometer when rPT cells were exposed to Cd for 12h. Then we demonstrated that Cd enhanced the protein levels of active calpain-1 and caspase-3 in rPT cells. Pretreatment with a cytosolic Ca 2+ chelator, 1,2-Bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM), markedly blocked the up-regulation of active calpain-1 and caspase-3 and inhibited the apoptosis induced by Cd. Further, rPT cells were pretreated with a cell-permeable selective calpain-1 inhibitor, 3-(4-iodophenyl)-2-mercapto-(Z)-2-propenoic acid (PD150606) and caspase-3 inhibitor, N-Acetyl-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO), respectively. PD150606 significantly attenuated the up-regulation of active caspase-3 and the apoptosis induced by Cd. As expected, inhibition of active caspase-3 by Ac-DEVD-CHO decreased the apoptosis induced by Cd. Taken together, it could be concluded that [Ca 2+ ] c elevation did act as a pro-apoptotic signal in Cd-induced cytotoxicity of rPT cells, triggered calpain-1 and caspase-3 activation in turn, and induced apoptosis of rPT cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Reduction of Cadmium Uptake of Rice Plants Using Soil Amendments in High Cadmium Contaminated Soil: A Pot Experiment

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Dian Siswanto

2013-05-01

Full Text Available The aims of this study were to investigate the effect of agricultural residues on reducing cadmium uptake in rice plants. The rice plants growing on no cadmium/free cadmium soils (N, Cd soils (Cds, and Cd soils each amended with 1% w/w of coir pith (CP, coir pith modified with sodium hydroxide (CPm and corncob (CC under high cadmium contaminated soil with an average 145 mg Cd kg-1 soil were investigated. The results showed that the cumulative transpiration of rice grown in various treatments under high cadmium contaminated soil followed the order: Cds > CPm ≥ CP ≥ CC. These transpirations directly influenced cadmium accumulation in shoots and husks of rice plants. The CC and CP seemed to work to reduce the cadmium uptake by rice plants indicated by accumulated cadmium in the husk that were 2.47 and 7.38 mg Cd kg-1 dry weight, respectively. Overall, transpiration tended to drive cadmium accumulation in plants for rice grown in high cadmium contaminated soil. The more that plants uptake cadmium, the lower cadmium that remains in the soil.

Endocytosis of a functionally enhanced GFP-tagged transferrin receptor in CHO cells.

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Qi He

Full Text Available The endocytosis of transferrin receptor (TfR has served as a model to study the receptor-targeted cargo delivery system for cancer therapy for many years. To accurately evaluate and optically measure this TfR targeting delivery in vitro, a CHO cell line with enhanced green fluorescent protein (EGFP-tagged human TfR was established. A chimera of the hTfR and EGFP was engineered by fusing EGFP to the amino terminus of hTfR. Data were provided to demonstrate that hTfR-EGFP chimera was predominantly localized on the plasma membrane with some intracellular fluorescent structures on CHO cells and the EGFP moiety did not affect the endocytosis property of hTfR. Receptor internalization occurred similarly to that of HepG2 cells expressing wild-type hTfR. The internalization percentage of this chimeric receptor was about 81 ± 3% of wild type. Time-dependent co-localization of hTfR-EGFP and PE-conjugated anti-hTfR mAb in living cells demonstrated the trafficking of mAb-receptor complexes through the endosomes followed by segregation of part of the mAb and receptor at the late stages of endocytosis. The CHO-hTfR cells preferentially took up anti-hTfR mAb conjugated nanoparticles. This CHO-hTfR cell line makes it feasible for accurate evaluation and visualization of intracellular trafficking of therapeutic agents conjugated with transferrin or Abs targeting the hTfRs.

Zinc and cadmium monosalicylates

International Nuclear Information System (INIS)

Kharitonov, Yu.Ya.; Tujebakhova, Z.K.

1984-01-01

Zinc and cadmium monosalicylates of the composition MSal, where M-Zn or Cd, Sal - twice deprotonated residue of salicylic acid O-HOC 6 H 4 COOH (H 2 Sal), are singled out and characterized. When studying thermograms, thermogravigrams, IR absorption spectra, roentgenograms of cadmium salicylate compounds (Cd(OC 6 H 4 COO) and products of their thepmal transformations, the processes of thermal decomposition of the compounds have been characterized. The process of cadmium monosalicylate decomposition takes place in one stage. Complete loss of salicylate acido group occurs in the range of 320-460 deg. At this decomposition stage cadmium oxide is formed. A supposition is made that cadmium complex has tetrahedral configuration, at that, each salicylate group plays the role of tetradentate-bridge ligand. The compound evidently has a polymer structure

Cadmium-sensitive electrode based on tetracetone derivatives of p-tert-butylcalix[8]arene

Energy Technology Data Exchange (ETDEWEB)

Dernane, C. [Université de Jijel, Laboratoire de Matériaux: Elaborations-Propriétés-Applications, BP 98, Ouled Aissa, 18000 Jijel (Algeria); Zazoua, A., E-mail: azazoua@yahoo.fr [Université de Jijel, Laboratoire de Matériaux: Elaborations-Propriétés-Applications, BP 98, Ouled Aissa, 18000 Jijel (Algeria); Kazane, I. [Université de Jijel, Laboratoire de Matériaux: Elaborations-Propriétés-Applications, BP 98, Ouled Aissa, 18000 Jijel (Algeria); Jaffrezic-Renault, N. [Université de Lyon, LSA-UMR 5180 CNRS, Université Claude Bernard Lyon 1, 69622 Villeurbanne cedex (France)

2013-10-15

The performance of a cadmium-sensitive electrode based on the tetracetone derivatives of p-tert butylcalix[8]arene was investigated. The ion-sensitivity of the calix[8]arene was examined via cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), X-ray photoelectron spectrometry, UV/Vis spectroscopy and FT-IR spectroscopy. The sensitive membrane containing the active ionophore was cast onto the surface of a gold electrode. The electrode exhibited a linear relationship between the charge transfer resistance (R{sub ct}) and the logarithm of the detected ion concentration. The cathodic peak at a potential of 0.56 V increased linearly as the Cd{sup 2+} ion concentration increased. The detection limit of the device reached 10{sup −7} M with high sensitivity toward cadmium. - Highlights: • The performances of cadmium-sensitive electrode were investigated. • The sensitive membrane was casted on the surface of a gold electrode. • The electrode showed a linear relationship between the R{sub ct} and the ion concentration. • The detection limit of the device was 10{sup −7} M with high sensitivity toward cadmium.

An unexpected caffeine-enhanced survival in x-ray-sensitive variant cells

International Nuclear Information System (INIS)

Utsumi, Hiroshi

1985-01-01

The sensitivity of normal Chinese hamster cell lines, V79 and CHO, mouse cell lines, L5178Y and L, and human HeLa cells to the killing effect of x-ray is enhanced with addition of caffeine following x-ray irradiation in a dose-dependent fashion. However, the survival rate of variant cell (V79-AL162/S-10) increased with addition of low concentration of caffeine (caffeine-enhanced survival phenomenon). Therefore, the effects of protein synthesis-inhibiting agents, such as cycloheximide and puromycin, on caffeine-enhanced survival phenomenon were examined. This phenomenon was completely abolished by the inhibitory agents, but not abolished by DNA synthesis-damaging agents, such as excess thymidine and aphidicolin. DNA-damaging physiochemical factors, such as neutrons, U.V., methyl methanesulfonate and mitomycin C, were examined in relation to variant cells' sensitivity and caffeine-enhanced survival phenomenon. V79-AL162/S-10 cells showed high sensitivity to the killing effect of mitomycin C, but their survival rate returned to the rate of normal V79-B310H cells with addition of caffeine. (Namekawa, K.)

Cadmium in blood and hypertension

Energy Technology Data Exchange (ETDEWEB)

Eum, Ki-Do; Lee, Mi-Sun [Department of Environmental Health, Graduate School of Public Health and Institute of Health and Environment, Seoul National University, Seoul (Korea, Republic of); Paek, Domyung [Department of Environmental Health, Graduate School of Public Health and Institute of Health and Environment, Seoul National University, Seoul (Korea, Republic of)], E-mail: paekdm@snu.ac.kr

2008-12-15

Objectives:: This study is to examine the effect of cadmium exposure on blood pressure in Korean general population. Methods:: The study population consisted of 958 men and 944 women who participated in the 2005 Korean National Health and Nutrition Examination Survey (KNHANES), in which blood pressure and blood cadmium were measured from each participant. Results:: The mean blood cadmium level was 1.67 {mu}g/L (median level 1.55). The prevalence of hypertension was 26.2%. The blood cadmium level was significantly higher among those subjects with hypertension than those without (mean level 1.77 versus 1.64 {mu}g/dL). After adjusting for covariates, the odds ratio of hypertension comparing the highest to the lowest tertile of cadmium in blood was 1.51 (95% confidence interval 1.13 to 2.05), and a dose-response relationship was observed. Systolic, diastolic, and mean arterial blood pressure were all positively associated with blood cadmium level, and this effect of cadmium on blood pressure was markedly stronger when the kidney function was reduced. Conclusions:: Cadmium exposures at the current level may have increased the blood pressure of Korean general population.

Cadmium in blood and hypertension

International Nuclear Information System (INIS)

Eum, Ki-Do; Lee, Mi-Sun; Paek, Domyung

2008-01-01

Objectives:: This study is to examine the effect of cadmium exposure on blood pressure in Korean general population. Methods:: The study population consisted of 958 men and 944 women who participated in the 2005 Korean National Health and Nutrition Examination Survey (KNHANES), in which blood pressure and blood cadmium were measured from each participant. Results:: The mean blood cadmium level was 1.67 μg/L (median level 1.55). The prevalence of hypertension was 26.2%. The blood cadmium level was significantly higher among those subjects with hypertension than those without (mean level 1.77 versus 1.64 μg/dL). After adjusting for covariates, the odds ratio of hypertension comparing the highest to the lowest tertile of cadmium in blood was 1.51 (95% confidence interval 1.13 to 2.05), and a dose-response relationship was observed. Systolic, diastolic, and mean arterial blood pressure were all positively associated with blood cadmium level, and this effect of cadmium on blood pressure was markedly stronger when the kidney function was reduced. Conclusions:: Cadmium exposures at the current level may have increased the blood pressure of Korean general population

Genetic association analysis of ATP binding cassette protein family reveals a novel association of ABCB1 genetic variants with epilepsy risk, but not with drug-resistance.

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Shabeesh Balan

Full Text Available Epilepsy constitutes a heterogeneous group of disorders that is characterized by recurrent unprovoked seizures due to widely different etiologies. Multidrug resistance remains a major issue in clinical epileptology, where one third of patients with epilepsy continue to have seizures. Role of efflux transporters in multidrug resistant epilepsy has been attributed to drug-resistant epilepsy although, with discrepant observation in genetic studies. These discrepancies could be attributed to variety of factors such as variable definition of the anti-epileptic drug (AED-resistance, variable epilepsy phenotypes and ethnicities among the studies. In the present study we inquired the role of multidrug transporters ABCB1 and ABCG2 variants in determining AED-resistance and susceptibility to epilepsy in three well-characterized cohorts comprising of mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS (prototype for AED-resistant epilepsy; juvenile myoclonic epilepsy (JME (prototype for AED-responsive epilepsy; and healthy non-epileptic controls, in 738 subjects of Malayalam speaking south Indian ancestry. ABCB1 and ABCG2 variants were not found to be associated with drug resistance when AED-resistant and AED-responsive cohorts were compared. However, a significant association was observed between ABCB1 (C3435T rs1045642 and risk of having epilepsy (MTLE-HS and JME pooled cohort; genotypic p-value = 0.0002; allelic p-value = 0.004. This association was seen persistent with MTLE-HS (genotypic p-value = 0.0008; allelic p-value = 0.004 and also with JME (genotypic p-value = 0.01; allelic p-value = 0.05 cohort individually. In-silico functional prediction indicated that ABCB1 rs1045642 has a deleterious impact on protein coding function and in splicing regulation. We conclude that the ABCB1 and ABCG2 variants do not confer to AED-resistance in the study population. However, ABCB1 rs1045642 increases vulnerability to epilepsy with greater tendency

Cadmium induces cadmium-tolerant gene expression in the filamentous fungus Trichoderma harzianum.

Science.gov (United States)

Cacciola, Santa O; Puglisi, Ivana; Faedda, Roberto; Sanzaro, Vincenzo; Pane, Antonella; Lo Piero, Angela R; Evoli, Maria; Petrone, Goffredo

2015-11-01

The filamentous fungus Trichoderma harzianum, strain IMI 393899, was able to grow in the presence of the heavy metals cadmium and mercury. The main objective of this research was to study the molecular mechanisms underlying the tolerance of the fungus T. harzianum to cadmium. The suppression subtractive hybridization (SSH) method was used for the characterization of the genes of T. harzianum implicated in cadmium tolerance compared with those expressed in the response to the stress induced by mercury. Finally, the effects of cadmium exposure were also validated by measuring the expression levels of the putative genes coding for a glucose transporter, a plasma membrane ATPase, a Cd(2+)/Zn(2+) transporter protein and a two-component system sensor histidine kinase YcbA, by real-time-PCR. By using the aforementioned SSH strategy, it was possible to identify 108 differentially expressed genes of the strain IMI 393899 of T. harzianum grown in a mineral substrate with the addition of cadmium. The expressed sequence tags identified by SSH technique were encoding different genes that may be involved in different biological processes, including those associated to primary and secondary metabolism, intracellular transport, transcription factors, cell defence, signal transduction, DNA metabolism, cell growth and protein synthesis. Finally, the results show that in the mechanism of tolerance to cadmium a possible signal transduction pathway could activate a Cd(2+)/Zn(2+) transporter protein and/or a plasma membrane ATPase that could be involved in the compartmentalization of cadmium inside the cell.

Preparation and study of the properties of indium phosphide thin films impregnated with cadmium and zinc

International Nuclear Information System (INIS)

Moutinho, H.R.

1984-01-01

Indium phosphide thin films were deposited by vacuum evaporation of indium and phosphorous, using the three-temperature method. The effects of the introduction of cadmium and zinc, group II impurities, on the properties of these films were studied. The introduction of cadmium was achieved by coevaporation of this element during the film deposition. The introduction of zinc was done by diffusion of this element in intrinsic films. Analyses of these films were carried out by the study of the composition, morphology, structure, optical properties and electrical properties. The introduction of cadmium led to the reduction of grain size and increase in the bandgap and in certain cases, even change in morphology. Phases of CdP2 and β-CdP2 were detected and the resistivity increased by some orders of magnitude. The introduction of zinc did not change the morphology, crystalline structure and bandgap. However, a new energy level corresponding to the zinc acceptor level was found and the resistivity increased by some orders of magnitude. (Author) [pt

Isolation of Burkholderia cepacia JB12 from lead- and cadmium-contaminated soil and its potential in promoting phytoremediation with tall fescue and red clover.

Science.gov (United States)

Jin, Zhong Min; Sha, Wei; Zhang, Yan Fu; Zhao, Jing; Ji, Hongyang

2013-07-01

Phytoremediation combined with suitable microorganisms and biodegradable chelating agents can be a means of reclaiming lands contaminated by toxic heavy metals. We investigated the ability of a lead- and cadmium-resistant bacterial strain (JB12) and the biodegradable chelator ethylenediamine-N,N'-disuccinic acid (EDDS) to improve absorption of these metals from soil by tall fescue and red clover. Strain JB12 was isolated from contaminated soil samples, analysed for lead and cadmium resistance, and identified as Burkholderia cepacia. Tall fescue and red clover were grown in pots to which we added JB12, (S,S)-EDDS, combined JB12 and EDDS, or water only. Compared with untreated plants, the biomass of plants treated with JB12 was significantly increased. Concentrations of lead and cadmium in JB12-treated plants increased significantly, with few exceptions. Plants treated with EDDS responded variably, but in those treated with combined EDDS and JB12, heavy metal concentrations increased significantly in tall fescue and in the aboveground parts of red clover. We conclude that JB12 is resistant to lead and cadmium. Its application to the soil improved the net uptake of these heavy metals by experimental plants. The potential for viable phytoremediation of lead- and cadmium-polluted soils with tall fescue and red clover combined with JB12 was further enhanced by the addition of EDDS.

Effects of cadmium and mycorrhizal fungi on growth, fitness, and cadmium accumulation in flax (Linum usitatissimum; Linaceae).

Science.gov (United States)

Hancock, Laura M S; Ernst, Charlotte L; Charneskie, Rebecca; Ruane, Lauren G

2012-09-01

Agricultural soils have become contaminated with a variety of heavy metals, including cadmium. The degree to which soil contaminants affect plants may depend on symbiotic relationships between plant roots and soil microorganisms. We examined (1) whether mycorrhizal fungi counteract the potentially negative effects of cadmium on the growth and fitness of flax (Linum usitatissimum) and (2) whether mycorrhizal fungi affect the accumulation of cadmium within plant parts. Two flax cultivars (Linott and Omega) were grown in three soil cadmium environments (0, 5, and 15 ppm). Within each cadmium environment, plants were grown in either the presence or absence of mycorrhizal fungi. Upon senescence, we measured growth and fitness and quantified the concentration of cadmium within plants. Soil cadmium significantly decreased plant fitness, but did not affect plant growth. Mycorrhizal fungi, which were able to colonize roots of plants growing in all cadmium levels, significantly increased plant growth and fitness. Although mycorrhizal fungi counteracted the negative effects of cadmium on fruit and seed production, they also enhanced the concentration of cadmium within roots, fruits, and seeds. The degree to which soil cadmium affects plant fitness and the accumulation of cadmium within plants depended on the ability of plants to form symbiotic relationships with mycorrhizal fungi. The use of mycorrhizal fungi in contaminated agricultural soils may offset the negative effects of metals on the quantity of seeds produced, but exacerbate the accumulation of these metals in our food supply.

The Thr92Ala deiodinase type 2 (DIO2) variant is not associated with type 2 diabetes or indices of insulin resistance in the old order of Amish.

Science.gov (United States)

Mentuccia, Daniela; Thomas, Matthew J; Coppotelli, Giuseppe; Reinhart, Laurie J; Mitchell, Braxton D; Shuldiner, Alan R; Celi, Francesco S

2005-11-01

A common polymorphism of the type 2 deiodinase gene (Thr92Ala DIO2) was found to be associated with insulin resistance in a mixed Caucasian population. The aim of this study was to investigate the association of the Thr92Ala DIO2 variant to indices of insulin resistance in the Old Order Amish. A genotype-phenotype association study was performed at the research clinic in Strasburg, Pennsylvania, and the molecular genetics laboratory at the University of Maryland, Baltimore, Maryland, and the National Institutes of Health, Bethesda, Maryland. A total of 1,268 subjects participated in the Amish Family Diabetes Study. An association among the Thr92Ala DIO2 variant and type 2 diabetes, indices of insulin resistance (HOMA-IR), insulin secretion, free thyroid hormones, and thyrotropin (TSH) was found. No association was found among the Thr92Ala DIO2 variant and type 2 diabetes, impaired glucose tolerance, or body mass index (BMI) in the Amish. In nondiabetics (n = 747), the Ala92 allele tended to be associated with decreased rather then increased insulin secretion. No differences were observed in thyroid hormones or TSH. Contrary to prior findings, the Thr92Ala DIO2 variant tends to be associated with increased rather then decreased insulin sensitivity in the Amish. These findings could be secondary to a different genetic background or to environmental factors specific for this population.

Optimization of cell line development in the GS-CHO expression system using a high-throughput, single cell-based clone selection system.

Science.gov (United States)

Nakamura, Tsuyoshi; Omasa, Takeshi

2015-09-01

Therapeutic antibodies are commonly produced by high-expressing, clonal and recombinant Chinese hamster ovary (CHO) cell lines. Currently, CHO cells dominate as a commercial production host because of their ease of use, established regulatory track record, and safety profile. CHO-K1SV is a suspension, protein-free-adapted CHO-K1-derived cell line employing the glutamine synthetase (GS) gene expression system (GS-CHO expression system). The selection of high-producing mammalian cell lines is a crucial step in process development for the production of therapeutic antibodies. In general, cloning by the limiting dilution method is used to isolate high-producing monoclonal CHO cells. However, the limiting dilution method is time consuming and has a low probability of monoclonality. To minimize the duration and increase the probability of obtaining high-producing clones with high monoclonality, an automated single cell-based clone selector, the ClonePix FL system, is available. In this study, we applied the high-throughput ClonePix FL system for cell line development using CHO-K1SV cells and investigated efficient conditions for single cell-based clone selection. CHO-K1SV cell growth at the pre-picking stage was improved by optimizing the formulation of semi-solid medium. The efficiency of picking and cell growth at the post-picking stage was improved by optimization of the plating time without decreasing the diversity of clones. The conditions for selection, including the medium formulation, were the most important factors for the single cell-based clone selection system to construct a high-producing CHO cell line. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Relationship of radiation sensitivity and aberrant DNA synthesis in repair deficient CHO cells

International Nuclear Information System (INIS)

Newman, C.N.; Hagler, H.; Miller, J.H.

1986-11-01

Comparison of alkaline sucrose gradient profiles of pulse-labeled DNA from a normal CHO cell line and its radiation-sensitive mutant, xrs-5, reveals significant differences in the replicon elongation/maturation process in these two cells. During a one hr period of growth subsequent to labeling, the molecular weight of pulse-labeled DNA from the mutant cell increases considerably more rapidly than that of the parent cell. For xrs-5, the presence of 2 mM deoxycytidine (CdR) in the culture medium reduces the replication rate to one approaching that of the parent cell growing in the standard medium. Corresponding uv resistance of the mutant likewise increases to nearly that of the parent cell line. These results suggest that the locus conferring radiation sensitivity to xrs-5 affects the DNA replisome complex and that replicative activity and radiation sensitivity are jointly modulated by CdR. 19 refs., 4 figs

Silver nanoparticle induced cytotoxicity, oxidative stress, and DNA damage in CHO cells

Energy Technology Data Exchange (ETDEWEB)

Awasthi, Kumud Kant [University of Rajasthan, Department of Zoology (India); Awasthi, Anjali; Kumar, Narender; Roy, Partha [Indian Institute of Technology Roorkee, Department of Biotechnology (India); Awasthi, Kamlendra, E-mail: kamlendra.awasthi@gmail.com [Malaviya National Institute of Technology, Department of Physics (India); John, P. J., E-mail: placheriljohn@yahoo.com [University of Rajasthan, Department of Zoology (India)

2013-09-15

Silver nanoparticles (Ag NPs) are being used increasingly in wound dressings, catheters, and in various household products due to their antimicrobial activity. The present study reports the toxicity evaluation of synthesized and well characterized Ag NPs using Chinese hamster ovary (CHO) cells. The UV-Vis spectroscopy reveals the formation of silver nanoparticles by exhibiting the typical surface plasmon absorption maxima at 408-410 nm. Transmission electron microscopy (TEM) reveals that the average diameter of silver nanoparticles is about 5.0 {+-} 1.0 nm and that they have spherical shape. Cell visibility and cell viability percentage show dose-dependent cellular toxicity of Ag NPs. The half maximal inhibitory concentration (IC{sub 50}) for CHO cells is 68.0 {+-} 2.65 {mu}g/ml after 24 h Ag NPs exposure. Toxicity evaluations, including cellular morphology, mitochondrial function (MTT assay), reactive oxygen species (ROS), and DNA fragmentation assay (Ladder pattern) were assessed in unexposed CHO cells (control) and the cells exposed to Ag NPs concentrations of 15, 30, and 60 {mu}g/ml for 24 h. The findings may assist in the designing of Ag NPs for various applications and provide insights into their toxicity.

Expression of an "Arabidopsis" Ca(2+)/H(+) antiporter CAX1 variant in petunia enhances cadmium tolerance and accumulation

Science.gov (United States)

Phytoremediation is a cost-effective and minimally invasive technology to cleanse soils contaminated with heavy metals. However, few plant species are suitable for phytoremediation of metals such as cadmium (Cd). Genetic engineering offers a powerful tool to generate plants that can hyperaccumulate ...

Cadmium Alternatives

Science.gov (United States)

2012-08-01

carcinogenic, leachable Trivalent and non- chrome passivates generally struggle with conductivity Major Differences in Trivalent vs. Hexavalent Passivates...for Change Cadmium passivated with hexavalent chromium has been in use for many decades Cadmium is toxic, and is classified as a priority...Executive Orders 13514 & 13423 DoD initiatives – Young memo (April 2009) DFAR restricting use of hexavalent chromium Allows the use of hexavalent

Association mapping to discover significant marker-trait associations for resistance against fusarium wilt variant 2 in pigeonpea [Cajanus cajan (L.) Millspaugh] using SSR markers.

Science.gov (United States)

Patil, Prakash G; Dubey, Jyotirmay; Bohra, Abhishek; Mishra, R K; Saabale, P R; Das, Alok; Rathore, Meenal; Singh, N P

2017-08-01

Pigeonpea production is severely constrained by wilt disease caused by Fusarium udum. In the current study, we discover the putative genomic regions that control resistance response to variant 2 of fusarium wilt using association mapping approach. The association panel comprised of 89 diverse pigeonpea genotypes including seven varieties, three landraces and 79 germplasm lines. The panel was screened rigorously for 3 consecutive years (2013-14, 2014-15 and 2015-2016) against variant 2 in a wilt-sick field. A total of 65 pigeonpea specific hypervariable SSR markers (HASSRs) were screened representing seven linkage groups and 29 scaffolds of the pigeonpea genome. A total of 181 alleles were detected, with average values of gene diversity and polymorphism information content (PIC) of 0.55 and 0.47, respectively. Further analysis using model based (STRUCTURE) and distance based (clustering) approaches separated the entire pigeonpea collection into two distinct subgroups (K = 2). The marker trait associations (MTAs) were established based on three-year wilt incidence data and SSR dataset using a unified mixed linear model. Consequently, six SSR markers were identified, which were significantly associated with wilt resistance and explained up to 6% phenotypic variance (PV) across the years. Among these SSRs, HASSR18 was found to be the most stable and significant, accounting for 5-6% PV across the years. To the best of our knowledge, this is the first report of identification of favourable alleles for resistance to variant 2 of Fusarium udum in pigeonpea using association mapping. The SSR markers identified here will greatly facilitate marker assisted resistance breeding against fusarium wilt in pigeonpea.

Cadmium exposure in the Swedish environment

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-03-01

This report gives a thorough description of cadmium in the Swedish environment. It comprises three parts: Cadmium in Sweden - environmental risks;, Cadmium in goods - contribution to environmental exposure;, and Cadmium in fertilizers, soil, crops and foods - the Swedish situation. Separate abstracts have been prepared for all three parts

Androgen receptor variant-7: an important predictive biomarker in castrate resistant prostate cancer

Directory of Open Access Journals (Sweden)

Oliver Sartor

2015-06-01

Full Text Available The recent manuscript in New England Journal of Medicine by Antonarakis et al. [1] has important clinical implications. This study evaluates mRNA expression of a particular androgen receptor splice variant-7 (AR-V7, in circulating tumor cells (CTCs from metastatic castrate-resistant prostate cancer (mCRPC patients receiving enzalutamide or abiraterone. The findings were striking, none of the 18 patients with detectable AR-V7 in CTCs had prostate-specific antigen (PSA responses. Further, the median time to PSA progression after enzalutamide or abiraterone treatment was only 1.3-1.4 months in AR-V7-positive patients as compared to 5.3-6.1 months in AR-V7 negative patients. AR-V7 in CTCs was also associated with shorter survival.

Rapid protein production from stable CHO cell pools using plasmid vector and the cumate gene-switch.

Science.gov (United States)

Poulain, Adeline; Perret, Sylvie; Malenfant, Félix; Mullick, Alaka; Massie, Bernard; Durocher, Yves

2017-08-10

To rapidly produce large amounts of recombinant proteins, the generation of stable Chinese Hamster Ovary (CHO) cell pools represents a useful alternative to large-scale transient gene expression (TGE). We have developed a cell line (CHO BRI/rcTA ) allowing the inducible expression of recombinant proteins, based on the cumate gene switch. After the identification of optimal plasmid DNA topology (supercoiled vs linearized plasmid) for PEIpro™ mediated transfection and of optimal conditions for methionine sulfoximine (MSX) selection, we were able to generate CHO BRI/rcTA pools producing high levels of recombinant proteins. Volumetric productivities of up to 900mg/L were reproducibly achieved for a Fc fusion protein and up to 350mg/L for an antibody after 14days post-induction in non-optimized fed-batch cultures. In addition, we show that CHO pool volumetric productivities are not affected by a freeze-thaw cycle or following maintenance in culture for over one month in the presence of MSX. Finally, we demonstrate that volumetric protein production with the CR5 cumate-inducible promoter is three- to four-fold higher than with the human CMV or hybrid EF1α-HTLV constitutive promoters. These results suggest that the cumate-inducible CHO BRI/rcTA stable pool platform is a powerful and robust system for the rapid production of gram amounts of recombinant proteins. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Improving the representation of modal choice into bottom-up optimization energy system models - The MoCho-TIMES model

DEFF Research Database (Denmark)

Tattini, Jacopo; Ramea, Kalai; Gargiulo, Maurizio

2018-01-01

and mathematical expressions required to develop the approach. This study develops MoCho-TIMES in the standalone transportation sector of TIMES-DK, the integrated energy system model for Denmark. The model is tested for the Business as Usual scenario and for four alternative scenarios that imply diverse......This study presents MoCho-TIMES, an original methodology for incorporating modal choice into energy-economy-environment-engineering (E4) system models. MoCho-TIMES addresses the scarce ability of E4 models to realistically depict behaviour in transport and allows for modal shift towards transit...

Effects of Different Dietary Cadmium Levels on Growth and Tissue Cadmium Content in Juvenile Parrotfish,

Directory of Open Access Journals (Sweden)

Okorie E. Okorie

2014-01-01

Full Text Available This feeding trial was carried out to evaluate the effects of different dietary cadmium levels on growth and tissue cadmium content in juvenile parrotfish, Oplegnathus fasciatus, using cadmium chloride (CdCl2 as the cadmium source. Fifteen fish averaging 5.5±0.06 g (mean±SD were randomly distributed into each of twenty one rectangular fiber tanks of 30 L capacity. Each tank was then randomly assigned to one of three replicates of seven diets containing 0.30 (C0, 21.0 (C21, 40.7 (C41, 83.5 (C83, 162 (C162, 1,387 (C1,387 and 2,743 (C2,743 mg cadmium/kg diet. At the end of sixteen weeks of feeding trial, weight gain (WG, specific growth rate (SGR and feed efficiency (FE of fish fed C21 were significantly higher than those of fish fed C83, C162, C1,387 and C2,743 (p<0.05. Weight gain, SGR and FE of fish fed C0, C21 and C41 were significantly higher than those of fish fed C162, C1,387 and C2,743. Protein efficiency ratio of fish fed C0, C21 and C41 were significantly higher than those of fish fed C1,387 and C2,743. Average survival of fish fed C0, C21, C41 and C162 were significantly higher than that of fish fed C2,743. Tissue cadmium concentrations increased with cadmium content of diets. Cadmium accumulated the most in liver, followed by gill and then muscle. Muscle, gill and liver cadmium concentrations of fish fed C0, C21, C41 and C83 were significantly lower than those of fish fed C162, C1,387 and C2,743. Based on the ANOVA results of growth performance and tissue cadmium concentrations the safe dietary cadmium level could be lower than 40.7 mg Cd/kg diet while the toxic level could be higher than 162 mg Cd/kg diet.

Effects of ingesting protein with various forms of carbohydrate following resistance-exercise on substrate availability and markers of anabolism, catabolism, and immunity

Directory of Open Access Journals (Sweden)

Greenwood Michael

2007-11-01

Full Text Available Abstract Background Ingestion of carbohydrate (CHO and protein (PRO following intense exercise has been reported to increase insulin levels, optimize glycogen resynthesis, enhance PRO synthesis, and lessen the immuno-suppressive effects of intense exercise. Since different forms of CHO have varying glycemic effects, the purpose of this study was to determine whether the type of CHO ingested with PRO following resistance-exercise affects blood glucose availability and insulin levels, markers of anabolism and catabolism, and/or general immune markers. Methods 40 resistance-trained subjects performed a standardized resistance training workout and then ingested in a double blind and randomized manner 40 g of whey PRO with 120 g of sucrose (S, honey powder (H, or maltodextrin (M. A non-supplemented control group (C was also evaluated. Blood samples were collected prior to and following exercise as well as 30, 60, 90, and 120 min after ingestion of the supplements. Data were analyzed by repeated measures ANOVA or ANCOVA using baseline values as a covariate if necessary. Results Glucose concentration 30 min following ingestion showed the H group (7.12 ± 0.2 mmol/L to be greater than S (5.53 ± 0.6 mmol/L; p uIU/mL, H (150.1 ± 25.39 uIU/mL, and M (154.8 ± 18.9 uIU/mL were greater than C (8.7 ± 2.9 uIU/mL as was AUC with no significant differences observed among types of CHO. No significant group × time effects were observed among groups in testosterone, cortisol, the ratio of testosterone to cortisol, muscle and liver enzymes, or general markers of immunity. Conclusion CHO and PRO ingestion following exercise significantly influences glucose and insulin concentrations. Although some trends were observed suggesting that H maintained blood glucose levels to a better degree, no significant differences were observed among types of CHO ingested on insulin levels. These findings suggest that each of these forms of CHO can serve as effective sources of

Synthesis of human prolactin in Chinese hamster ovary (CHO) cells

International Nuclear Information System (INIS)

Soares, Carlos Roberto Jorge

2000-01-01

Three different eukaryotic expression vectors, based on the same selectable gene marker (dhfr), have been used for dhf- CHO cells transfection to rapidly isolate stable cell lines capable of secreting high levels of recombinant human prolactin (rec-hPRL). Two vectors, one codifying a human prolactin (p658-hPRL) and the other a tag-prolactin (p658-tagPRL), contain the complete hepatitis B virus-X (HBV-X) gene coding for a viral transactivator and a sequence derived from the granulocyte-macrophage colony-stimulating factor (GM-CSF) that mediates selective dhfr mRNA degradation. These vectors have the advantage of rapidly obtaining stable cell lines without methotrexate amplification. The highest secretion obtained by these vectors was of approximately 10 μg hPRU10 6 cells/day. The other vector (pEDdc-hPRL) is based on a dicistronic expression system, containing an internal ribosome entry site isolated from the encephalomyocarditis (EMC) virus. This vector before amplification provided secretion levels at least 10 fold lower than that obtained with the other two vectors. However, after three steps of methotrexate amplification, it provided some clones able to secrete up to 30 μg hPRU10 6 cells/day. This is the first report describing the production and purification of rec-hPRL from CHO cells, obtaining secretion levels with both vectors higher than those reported so far for this hormone in other eukaryotic systems. CHO-derived rec-hPRL contained approximately 10 % of the glycosylated form, a value that is consistent with results reported for hPRL purified from the pituitary or from transformed murine C-127 cells. CHO-derived rec-hPRL was purified with good yield, obtaining also a good resolution between non-glycosylated and glycosylated prolactin. The latter, when its potency was determined via an in vitro bioassay, presented a 47 % lower bioactivity. A qualitative and quantitative analysis of these forms was also possible thanks to the setting up of a reversed

Exogenous Melatonin Confers Cadmium Tolerance by Counterbalancing the Hydrogen Peroxide Homeostasis in Wheat Seedlings

Directory of Open Access Journals (Sweden)

Jun Ni

2018-03-01

Full Text Available Melatonin has emerged as a research highlight regarding its important role in regulating plant growth and the adaptation to the environmental stresses. In this study, we investigated how melatonin prevented the cadmium toxicity to wheat seedlings. The results demonstrated that cadmium induced the expression of melatonin biosynthesis-related genes and cause a significant increase of endogenous melatonin level. Melatonin treatment drastically alleviated the cadmium toxicity, resulting in increased plant height, biomass accumulation, and root growth. Cadmium and senescence treatment significantly increased the endogenous level of hydrogen peroxide, which was strictly counterbalanced by melatonin. Furthermore, melatonin treatment caused a significant increase of GSH (reduced glutathione content and the GSH/GSSG (oxidized glutathione ratio. The activities of two key antioxidant enzymes, ascorbate peroxidase (APX and superoxide dismutase (SOD, but not catalase (CAT and peroxidase (POD, were specifically improved by melatonin. Additionally, melatonin not only promoted the primary root growth, but also drastically enhanced the capacity of the seedling roots to degrade the exogenous hydrogen peroxide. These results suggested that melatonin played a key role in maintaining the hydrogen peroxide homeostasis, via regulation of the antioxidant systems. Conclusively, this study revealed a crucial protective role of melatonin in the regulation of cadmium resistance in wheat.

Exogenous Melatonin Confers Cadmium Tolerance by Counterbalancing the Hydrogen Peroxide Homeostasis in Wheat Seedlings.

Science.gov (United States)

Ni, Jun; Wang, Qiaojian; Shah, Faheem Afzal; Liu, Wenbo; Wang, Dongdong; Huang, Shengwei; Fu, Songling; Wu, Lifang

2018-03-30

Melatonin has emerged as a research highlight regarding its important role in regulating plant growth and the adaptation to the environmental stresses. In this study, we investigated how melatonin prevented the cadmium toxicity to wheat seedlings. The results demonstrated that cadmium induced the expression of melatonin biosynthesis-related genes and cause a significant increase of endogenous melatonin level. Melatonin treatment drastically alleviated the cadmium toxicity, resulting in increased plant height, biomass accumulation, and root growth. Cadmium and senescence treatment significantly increased the endogenous level of hydrogen peroxide, which was strictly counterbalanced by melatonin. Furthermore, melatonin treatment caused a significant increase of GSH (reduced glutathione) content and the GSH/GSSG (oxidized glutathione) ratio. The activities of two key antioxidant enzymes, ascorbate peroxidase (APX) and superoxide dismutase (SOD), but not catalase (CAT) and peroxidase (POD), were specifically improved by melatonin. Additionally, melatonin not only promoted the primary root growth, but also drastically enhanced the capacity of the seedling roots to degrade the exogenous hydrogen peroxide. These results suggested that melatonin played a key role in maintaining the hydrogen peroxide homeostasis, via regulation of the antioxidant systems. Conclusively, this study revealed a crucial protective role of melatonin in the regulation of cadmium resistance in wheat.

Precision control of recombinant gene transcription for CHO cell synthetic biology.

Science.gov (United States)

Brown, Adam J; James, David C

2016-01-01

The next generation of mammalian cell factories for biopharmaceutical production will be genetically engineered to possess both generic and product-specific manufacturing capabilities that may not exist naturally. Introduction of entirely new combinations of synthetic functions (e.g. novel metabolic or stress-response pathways), and retro-engineering of existing functional cell modules will drive disruptive change in cellular manufacturing performance. However, before we can apply the core concepts underpinning synthetic biology (design, build, test) to CHO cell engineering we must first develop practical and robust enabling technologies. Fundamentally, we will require the ability to precisely control the relative stoichiometry of numerous functional components we simultaneously introduce into the host cell factory. In this review we discuss how this can be achieved by design of engineered promoters that enable concerted control of recombinant gene transcription. We describe the specific mechanisms of transcriptional regulation that affect promoter function during bioproduction processes, and detail the highly-specific promoter design criteria that are required in the context of CHO cell engineering. The relative applicability of diverse promoter development strategies are discussed, including re-engineering of natural sequences, design of synthetic transcription factor-based systems, and construction of synthetic promoters. This review highlights the potential of promoter engineering to achieve precision transcriptional control for CHO cell synthetic biology. Copyright © 2015. Published by Elsevier Inc.

Method for reducing ammonium and lactate production in cho cells

DEFF Research Database (Denmark)

2018-01-01

The present invention relates to modified producer cells for improved production of therapeutic proteins. Specifically, the inventors have found that removing genes involved in amino acid catabolism in Chinese Hamster Ovary (CHO) cells improves the cell growth and viability and likely also...

Site-specific integration in CHO cells mediated by CRISPR/Cas9 and homology-directed DNA repair pathway

DEFF Research Database (Denmark)

Lee, Jae Seong; Beuchert Kallehauge, Thomas; Pedersen, Lasse Ebdrup

2015-01-01

gene integration into site-specific loci in CHO cells using CRISPR/Cas9 genome editing system and compatible donor plasmid harboring a gene of interest (GOI) and short homology arms. This strategy has enabled precise insertion of a 3.7-kb gene expression cassette at defined loci in CHO cells following...

Effects of carbohydrate and branched-chain amino acid beverage ingestion during acute upper body resistance exercise on performance and postexercise hormone response.

Science.gov (United States)

Smith, JohnEric W; Krings, Ben M; Shepherd, Brandon D; Waldman, Hunter S; Basham, Steven A; McAllister, Matthew J

2018-05-01

The purpose of this investigation was to examine the individual and combined effects of ingesting carbohydrates (CHO) and branched-chain amino acids (BCAA) during high-volume upper body resistance exercise (RE) on markers of catabolism and performance. Thirteen resistance-trained males completed 4 experimental trials with supplementation, ingesting beverages containing CHO, BCAA, CHO+BCAA, or placebo (PLA) in a randomized, double-blind design. The beverages were ingested in 118-mL servings 6 times during an ∼60-min RE session consisting of bench press, bent-over row, incline press, and close-grip row. Each RE was performed with 5 sets of repetitions at 65% 1-repetition maximum until volitional fatigue. Blood samples were collected at baseline, immediately postexercise, and 60 min postexercise to assess glucose and insulin. Cortisol was assessed immediately and at 60 min postexercise. No significant performance benefits were observed for any RE. CHO+BCAA (152.4 ± 71.4 ng/mL) resulted in the lowest cortisol levels, which was lower than BCAA and PLA (193.7 ± 88.5, 182.8 ± 67.5 ng/mL, p BCAA and PLA (3.7 ± 2.0, 3.5 ± 1.8 mU/L, p BCAA (4.3 ± 2.5 mU/L, p = 0.339). There was no treatment effect for glucose, but glucose significantly increased from baseline to immediately postexercise and significantly decreased at 60 min postexercise. Ingesting beverages containing CHO with or without BCAA during upper body resistance exercise may promote a more favorable postexercise less catabolic environment.

Mechanisms of cadmium induced genomic instability

Energy Technology Data Exchange (ETDEWEB)

Filipic, Metka, E-mail: metka.filipic@nib.si [National Institute of Biology, Department for Genetic Toxicology and Cancer Biology, Ljubljana (Slovenia)

2012-05-01

Cadmium is an ubiquitous environmental contaminant that represents hazard to humans and wildlife. It is found in the air, soil and water and, due to its extremely long half-life, accumulates in plants and animals. The main source of cadmium exposure for non-smoking human population is food. Cadmium is primarily toxic to the kidney, but has been also classified as carcinogenic to humans by several regulatory agencies. Current evidence suggests that exposure to cadmium induces genomic instability through complex and multifactorial mechanisms. Cadmium dose not induce direct DNA damage, however it induces increase in reactive oxygen species (ROS) formation, which in turn induce DNA damage and can also interfere with cell signalling. More important seems to be cadmium interaction with DNA repair mechanisms, cell cycle checkpoints and apoptosis as well as with epigenetic mechanisms of gene expression control. Cadmium mediated inhibition of DNA repair mechanisms and apoptosis leads to accumulation of cells with unrepaired DNA damage, which in turn increases the mutation rate and thus genomic instability. This increases the probability of developing not only cancer but also other diseases associated with genomic instability. In the in vitro experiments cadmium induced effects leading to genomic instability have been observed at low concentrations that were comparable to those observed in target organs and tissues of humans that were non-occupationally exposed to cadmium. Therefore, further studies aiming to clarify the relevance of these observations for human health risks due to cadmium exposure are needed.

Mechanisms of cadmium induced genomic instability

International Nuclear Information System (INIS)

Filipič, Metka

2012-01-01

Cadmium is an ubiquitous environmental contaminant that represents hazard to humans and wildlife. It is found in the air, soil and water and, due to its extremely long half-life, accumulates in plants and animals. The main source of cadmium exposure for non-smoking human population is food. Cadmium is primarily toxic to the kidney, but has been also classified as carcinogenic to humans by several regulatory agencies. Current evidence suggests that exposure to cadmium induces genomic instability through complex and multifactorial mechanisms. Cadmium dose not induce direct DNA damage, however it induces increase in reactive oxygen species (ROS) formation, which in turn induce DNA damage and can also interfere with cell signalling. More important seems to be cadmium interaction with DNA repair mechanisms, cell cycle checkpoints and apoptosis as well as with epigenetic mechanisms of gene expression control. Cadmium mediated inhibition of DNA repair mechanisms and apoptosis leads to accumulation of cells with unrepaired DNA damage, which in turn increases the mutation rate and thus genomic instability. This increases the probability of developing not only cancer but also other diseases associated with genomic instability. In the in vitro experiments cadmium induced effects leading to genomic instability have been observed at low concentrations that were comparable to those observed in target organs and tissues of humans that were non-occupationally exposed to cadmium. Therefore, further studies aiming to clarify the relevance of these observations for human health risks due to cadmium exposure are needed.

Metabolite profiling of CHO cells: Molecular reflections of bioprocessing effectiveness

NARCIS (Netherlands)

Sellick, C.A.; Croxford, A.S.; Maqsood, A.R.; Stephens, G.M.; Westerhoff, H.V.; Goodacre, R.; Dickson, A.J.

2015-01-01

Whilst development of medium and feeds has provided major advances in recombinant protein production in CHO cells, the fundamental understanding is limited. We have applied metabolite profiling with established robust (GC-MS) analytics to define the molecular loci by which two yield-enhancing feeds

Cadmium in the biofuel system

International Nuclear Information System (INIS)

Aabyhammar, T.; Fahlin, M.; Holmroos, S.

1993-12-01

Removal of biofuel depletes the soil of important nutrients. Investigations are being made of possibilities to return most of these nutrients by spreading the ashes remaining after combustion in the forest or on field. Return of ashes implies that both beneficial and harmful substances are returned. This study has been conducted to illustrate that the return of cadmium implies the greatest risk for negative influences. The occurrence, utilization, emissions and effects of cadmium are discussed. The behaviour of cadmium in soil is discussed in detail. Flows and quantities of cadmium in Swedish society are reviewed. Flows and quantities of both total and plant available cadmium in the entire forest and arable areas of Sweden are given. A scenario for a bioenergy system of max 100 TWh is discussed. The cadmium flow in different biofuels and forest raw products, and anticipated amounts of ashes and cadmium concentrations, are calculated. Power production from biofuels is surveyed. Possibilities to clean ashes have been examined in laboratory experiments. Ashes and trace elements occurring as a result of the gasification of biofuels are reviewed. Strategies for handling ashes are discussed. Proposals on continued inputs in both the biological and technical sciences are made. 146 refs, 23 figs, 38 tabs

Pertussis serology: assessment of IgG anti-PT ELISA for replacement of the CHO cell assay*

Science.gov (United States)

DALBY, TINE; SØRENSEN, CHARLOTTE; PETERSEN, JESPER WESTPHAL; KROGFELT, KAREN ANGELIKI

2010-01-01

Dalby T, Sørensen C, Petersen JW, Krogfelt KA. Pertussis serology: assessment of IgG anti-PT ELISA for replacement of the CHO cell assay. APMIS 2010; 118: 968–72. Two types of serological assays are commonly used for the assessment of pertussis vaccine-induced antibodies; the Chinese hamster ovary cell (CHO cell) assay and the immunoglobulin G (IgG) anti pertussis toxin (PT) enzyme-linked immunosorbent assay (IgG anti-PT ELISA). Recently, both the techniques have been modified to improve performance with sera with interfering activity (CHO cell assay) or with heat-treated sera (IgG anti-PT ELISA). These two improved techniques were compared by the analysis of 100 individual serum samples from a previous clinical trial and 213 sera from a longitudinal serum collection from 20 Danish adults recently vaccinated with the Danish acellular pertussis vaccine. The comparison showed a significant linear correlation between the results of the two assays with a p-value of ELISA can be used as a replacement for the often troublesome and time-consuming CHO cell assay for the measurement of vaccine-induced human antibodies to PT. PMID:21091778

Osteopontin splice variants are differential predictors of breast cancer treatment responses

OpenAIRE

Zduniak, Krzysztof; Agrawal, Anil; Agrawal, Siddarth; Hossain, Md Monir; Ziolkowski, Piotr; Weber, Georg F.

2016-01-01

Background Osteopontin is a marker for breast cancer progression, which in previous studies has also been associated with resistance to certain anti-cancer therapies. It is not known which splice variants may mediate treatment resistance. Methods Here we analyze the association of osteopontin variant expression before treatment, differentiated according to immunohistochemistry with antibodies to exon 4 and to the osteopontin-c splice junction respectively, with the ensuing therapy responses i...

Prevalence of NS5B resistance-associated variants in treatment-naïve Asian patients with chronic hepatitis C.

Science.gov (United States)

Yang, Song; Xing, Huichun; Feng, Shenghu; Ju, Wei; Liu, Shunai; Wang, Xiaomei; Ou, Weini; Cheng, Jun; Pan, Calvin Q

2018-02-01

There is little information on the association between baseline non-structural protein (NS) 5b resistance-associated variants (RAVs) and treatment failure in hepatitis C patients. This study examined the frequencies of natural hepatitis C virus (HCV) NS5B resistance-associated variants (RAVs) in an Asian cohort. Samples from Asian HCV patients enrolled between October 2009 and September 2014 were analyzed for NS5B RAVs within the region from amino acid 230 to 371. Serum samples were tested by PCR genotyping, with sequence alignment performed using the neighbor-joining method. NS5B was detected by Sanger sequencing followed by Geno2pheno analysis. NS5B RAVs were detected in 80.52% (1199/1489) of patients; 68.4% (1019/1489) and 79.7% (1186/1489) were associated with resistance to sofosbuvir (SOF) and dasabuvir (DSV), respectively. These RAVs were present in 95% (1004/1058) of genotype 1b patients. When genotypes 1b and 2a were compared, SOF-associated RAVs were detected at a higher frequency in genotype 1b (94.8% [1004/1058] vs. 2.9% [9/309]; χ 2 = 1054.433, P C316H/N was more common in genotype 1b (94.7% [1002/1058] vs. 0% [0/309]; χ 2 = 1096.014, P C316Y/H/N/W was higher in genotype 1b (94.7% [1002/1058] vs. 0% [0/309]; χ 2 = 1096.014, P < 0.001). In conclusion, baseline SOF and DSV RAVs are common in Asian HCV patients and predominantly occur in genotype 1b.

ARP2, a novel pro-apoptotic protein expressed in epithelial prostate cancer LNCaP cells and epithelial ovary CHO transformed cells.

Science.gov (United States)

Mas-Oliva, Jaime; Navarro-Vidal, Enrique; Tapia-Vieyra, Juana Virginia

2014-01-01

Neoplastic epithelial cells generate the most aggressive types of cancers such as those located in the lung, breast, colon, prostate and ovary. During advanced stages of prostate cancer, epithelial cells are associated to the appearance of androgen-independent tumors, an apoptotic-resistant phenotype that ultimately overgrows and promotes metastatic events. We have previously identified and electrophysiologically characterized a novel Ca(2+)-permeable channel activated during apoptosis in the androgen-independent prostate epithelial cancer cell line, LNCaP. In addition, we reported for the first time the cloning and characterization of this channel-like molecule named apoptosis regulated protein 2 (ARP2) associated to a lethal influx of Ca(2+) in Xenopus oocytes. In the present study, LNCaP cells and Chinese hamster ovary cells (CHO cell line) transfected with arp2-cDNA are induced to undergo apoptosis showing an important impact on cell viability and activation of caspases 3 and 7 when compared to serum deprived grown cells and ionomycin treated cells. The subcellular localization of ARP2 in CHO cells undergoing apoptosis was studied using confocal microscopy. While apoptosis progresses, ARP2 initially localized in the peri-nuclear region of cells migrates with time towards the plasma membrane region. Based on the present results and those of our previous studies, the fact that ARP2 constitutes a novel cation channel is supported. Therefore, ARP2 becomes a valuable target to modulate the influx and concentration of calcium in the cytoplasm of epithelial cancer cells showing an apoptotic-resistant phenotype during the onset of an apoptotic event.

Staphylococcus aureus small colony variants are resistant to the antimicrobial peptide lactoferricin B.

Science.gov (United States)

Samuelsen, Orjan; Haukland, Hanne Husom; Kahl, Barbara C; von Eiff, Christof; Proctor, Richard A; Ulvatne, Hilde; Sandvik, Kjersti; Vorland, Lars H

2005-12-01

To determine whether Staphylococcus aureus small colony variants (SCVs) are resistant to the antimicrobial peptide lactoferricin B. To assess if deficiency in transmembrane potential, a common characteristic of SCVs that are haemin- or menadione-auxotrophs, affects the uptake of the peptide into the bacterial cytoplasm. A broth microdilution technique was used for susceptibility testing to determine the MIC of lactoferricin B for SCVs with three different auxotrophisms (haemin, menadione or thymidine) and their isogenic parent strains. Both clinical isolates and genetically defined mutants were used. The internalization of lactoferricin B in a hemB mutant and the respective parent strain was studied using transmission electron microscopy and immunogold labelling. All SCVs showed reduced susceptibility to lactoferricin B irrespective of their auxotrophy compared with their isogenic parent strains. The MIC for all SCVs was >256 mg/L, whereas the MICs for the parent strains ranged from 16-256 mg/L. Surprisingly, the hemB mutant contained significantly more lactoferricin B intracellularly than the respective parent strain. The resistance mechanism of SCVs towards the antimicrobial peptide lactoferricin B is presumably caused by the metabolic changes present in SCVs rather than by a changed transmembrane potential of SCVs or reduced uptake of the peptide.

Genetic complexity of fusidic acid-resistant small colony variants (SCV in Staphylococcus aureus.

Directory of Open Access Journals (Sweden)

Jonas Lannergård

Full Text Available FusE mutants are fusidic acid-resistant small colony variants (SCVs of Staphylococcus aureus that can be selected with aminoglycosides. All FusE SCVs have mutations in rplF, encoding ribosomal protein L6. However, individual FusE mutants including some with the same mutation in rplF display auxotrophy for either hemin or menadione, suggesting that additional mutations are involved. Here we show that FusE SCVs can be divided into three genetic sub-groups and that some carry an additional mutation, in one of the genes required for hemin biosynthesis, or in one of the genes required for menadione biosynthesis. Reversion analysis and genome sequencing support the hypothesis that these combinations of mutations in the rplF, hem, and/or men genes can account for the SCV and auxotrophic phenotypes of FusE mutants.

One-step generation of triple knockout CHO cell lines using CRISPR/Cas9 and fluorescent enrichment

DEFF Research Database (Denmark)

Grav, Lise Marie; Lee, Jae Seong; Thomsen, Signe Gerling

2015-01-01

The CRISPR/Cas9 genome editing technology has previously been shown to be a highly efficient tool for generating gene disruptions in CHO cells. In this study we further demonstrate the applicability and efficiency of CRISPR/Cas9 genome editing by disrupting FUT8, BAK and BAX simultaneously....... Taken together, multiplexing with CRISPR/Cas9 can accelerate genome engineering efforts in CHO cells even further....

Uptake and distribution of cadmium in corn

International Nuclear Information System (INIS)

Peel, J.W.; Vetter, R.J.; Christian, J.E.; Kessler, W.V.; McFee, W.W.

1978-01-01

The uptake and distribution of cadmium in corn (Zea mays) treated at various time intervals after planting and sampled at various times after treatment were measured. Cadmium was found to accumulate in all parts sampled. As shown in field studies, stems and leaves generally concentrated more cadmium than did husks, cobs, kernels, silks, or tassels. Samples of stems and leaves from corn treated 23 days after planting and sampled 5 days later exhibited higher concentrations of cadmium than samples taken 25, 45, 65, or 85 days after treatment. Concentrations generally decreased with time. Greenhouse studies showed that corn exposed to cadmium for the longest period of time accumulated the greatest total cadmium. The highest cadmium concentrations were found in the base or lowest leaves sampled 45 days after planting; this suggests a useful technique for quick screening corn crops for cadmium pollution

Alcohol vapor sensing by cadmium-doped zinc oxide thick films based chemical sensor

Science.gov (United States)

Zargar, R. A.; Arora, M.; Chackrabarti, S.; Ahmad, S.; Kumar, J.; Hafiz, A. K.

2016-04-01

Cadmium-doped zinc oxide nanoparticles were derived by simple chemical co-precipitation route using zinc acetate dihydrate and cadmium acetate dihydrate as precursor materials. The thick films were casted from chemical co-precipitation route prepared nanoparticles by economic facile screen printing method. The structural, morphological, optical and electrical properties of the film were characterized relevant to alcohol vapor sensing application by powder XRD, SEM, UV-VIS and DC conductivity techniques. The response and sensitivity of alcohol (ethanol) vapor sensor are obtained from the recovery curves at optimum working temperature range from 20∘C to 50∘C. The result shows that maximum sensitivity of the sensor is observed at 25∘C operating temperature. On varying alcohol vapor concentration, minor variation in resistance has been observed. The sensing mechanism of sensor has been described in terms of physical adsorption and chemical absorption of alcohol vapors on cadmium-doped zinc oxide film surface and inside film lattice network through weak hydrogen bonding, respectively.

Biological indicators of cadmium exposure and toxicity

Energy Technology Data Exchange (ETDEWEB)

Shaikh, Z A; Smith, L M

1986-01-01

The increasing environmental and occupational exposure of populations to cadmium creates the need for biological indicators of cadmium exposure and toxicity. The advantages and disadvantages of monitoring blood cadmium, urinary, fecal, hair, and tissue cadmium, serum creatine, beta 2-microglobulin, alpha 1-anti-trypsin and other proteins, and urinary amino acids, enzymes, total proteins, glucose, beta 2-microglobulin, retinol-binding protein, lysozyme, and metallothionein are discussed. It is concluded that urinary cadmium, metallothionein and beta 2-microglubulin may be used together to assess cadmium exposure and toxicity. 66 references.

Task-based detectability comparison of exponential transformation of free-response operating characteristic (EFROC) curve and channelized Hotelling observer (CHO)

Science.gov (United States)

Khobragade, P.; Fan, Jiahua; Rupcich, Franco; Crotty, Dominic J.; Gilat Schmidt, Taly

2016-03-01

This study quantitatively evaluated the performance of the exponential transformation of the free-response operating characteristic curve (EFROC) metric, with the Channelized Hotelling Observer (CHO) as a reference. The CHO has been used for image quality assessment of reconstruction algorithms and imaging systems and often it is applied to study the signal-location-known cases. The CHO also requires a large set of images to estimate the covariance matrix. In terms of clinical applications, this assumption and requirement may be unrealistic. The newly developed location-unknown EFROC detectability metric is estimated from the confidence scores reported by a model observer. Unlike the CHO, EFROC does not require a channelization step and is a non-parametric detectability metric. There are few quantitative studies available on application of the EFROC metric, most of which are based on simulation data. This study investigated the EFROC metric using experimental CT data. A phantom with four low contrast objects: 3mm (14 HU), 5mm (7HU), 7mm (5 HU) and 10 mm (3 HU) was scanned at dose levels ranging from 25 mAs to 270 mAs and reconstructed using filtered backprojection. The area under the curve values for CHO (AUC) and EFROC (AFE) were plotted with respect to different dose levels. The number of images required to estimate the non-parametric AFE metric was calculated for varying tasks and found to be less than the number of images required for parametric CHO estimation. The AFE metric was found to be more sensitive to changes in dose than the CHO metric. This increased sensitivity and the assumption of unknown signal location may be useful for investigating and optimizing CT imaging methods. Future work is required to validate the AFE metric against human observers.

Yeast PAH1-encoded phosphatidate phosphatase controls the expression of CHO1-encoded phosphatidylserine synthase for membrane phospholipid synthesis.

Science.gov (United States)

Han, Gil-Soo; Carman, George M

2017-08-11

The PAH1 -encoded phosphatidate phosphatase (PAP), which catalyzes the committed step for the synthesis of triacylglycerol in Saccharomyces cerevisiae , exerts a negative regulatory effect on the level of phosphatidate used for the de novo synthesis of membrane phospholipids. This raises the question whether PAP thereby affects the expression and activity of enzymes involved in phospholipid synthesis. Here, we examined the PAP-mediated regulation of CHO1 -encoded phosphatidylserine synthase (PSS), which catalyzes the committed step for the synthesis of major phospholipids via the CDP-diacylglycerol pathway. The lack of PAP in the pah1 Δ mutant highly elevated PSS activity, exhibiting a growth-dependent up-regulation from the exponential to the stationary phase of growth. Immunoblot analysis showed that the elevation of PSS activity results from an increase in the level of the enzyme encoded by CHO1 Truncation analysis and site-directed mutagenesis of the CHO1 promoter indicated that Cho1 expression in the pah1 Δ mutant is induced through the inositol-sensitive upstream activation sequence (UAS INO ), a cis -acting element for the phosphatidate-controlled Henry (Ino2-Ino4/Opi1) regulatory circuit. The abrogation of Cho1 induction and PSS activity by a CHO1 UAS INO mutation suppressed pah1 Δ effects on lipid synthesis, nuclear/endoplasmic reticulum membrane morphology, and lipid droplet formation, but not on growth at elevated temperature. Loss of the DGK1 -encoded diacylglycerol kinase, which converts diacylglycerol to phosphatidate, partially suppressed the pah1 Δ-mediated induction of Cho1 and PSS activity. Collectively, these data showed that PAP activity controls the expression of PSS for membrane phospholipid synthesis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Direct examination of cadmium bonding in rat tissues dosed with mine wastes and cadmium-containing solutions

International Nuclear Information System (INIS)

Diacomanolis, V.; Ng, J. C.; Sadler, R.; Harris, H. H.; Nomura, M.; Noller, B. N.

2010-01-01

Direct examination by XANES and EXAFS of metal bonding in tissue can be demonstrated by examining cadmium uptake and bonding in animal tissue maintained at cryogenic temperatures. XANES at the K-edge of cadmium were collected at the Photon Factory Advanced Ring (PF-AR), NW10A beam line at KEK-Tsukuba-Japan. Rats fed with 1g mine waste containing 8-400 mg/kg cadmium per 200g body weight (b.w.) or dosed by oral gavage with either cadmium chloride solution alone (at 6 mg/kg b.w.) or in combination with other salts (As, Cu or Zn), 5 days/week for 6 weeks, had 0.1-7.5 and 8-86 mg/kg cadmium in the liver or kidney, respectively. Rats given intraperitoneally (ip) or intravenously (iv) 1-4 times with 1 mg/kg b.w. cadmium solution had 30-120 mg/kg cadmium in the liver or kidney. Tissues from rats were kept and transferred at cryogenic temperature and XANES were recorded at 20 K. The spectra for rat liver samples suggested conjugation of cadmium with glutathione or association with the sulfide bond (Cd-S) of proteins and peptides. EXAFS of rat liver fed by Cd and Zn solutions showed that Cd was clearly bound to S ligands with an inter-atomic distance of 2.54 A ring for Cd-S that was similar to cadmium sulfide with an inter-atomic distance of 2.52 A ring for Cd-S. Liver or kidney of rats fed with mine wastes did not give an edge in the XANES spectra indicating little uptake of cadmium by the animals. Longer and higher dosing regimen may be required in order to observe the same Cd-S bond in the rat tissue from mine wastes, including confirmation by EXAFS.

Overcoming imatinib resistance using Src inhibitor CGP76030, Abl inhibitor nilotinib and Abl/Lyn inhibitor INNO-406 in newly established K562 variants with BCR-ABL gene amplification.

Science.gov (United States)

Morinaga, Koji; Yamauchi, Takahiro; Kimura, Shinya; Maekawa, Taira; Ueda, Takanori

2008-06-01

Because imatinib (IM) resistance in chronic myeloid leukemia is primarily caused by the re-establishment of Abl kinase, new inhibitors may be efficacious. We evaluated 3 new agents against 2 new K562 variants, IM-R1 and IM-R2 cells, which were developed having 7- and 27-fold greater IM resistance, respectively, than the parental K562 cells. Both variants possessed BCR-ABL gene amplification along with elevated levels of its transcript and protein. Greater BCR-ABL gene amplification was observed in IM-R2 cells than in IM-R1 cells, which was consistent with the higher mRNA and protein levels of Bcr-Abl, and ultimately correlated with the greater IM resistance in IM-R2 cells. No mutation in the Abl kinase domain was detected in either variant. Despite the absence of Lyn overexpression, the Src kinase inhibitor CGP76030 showed positive cooperability with IM in inhibiting cell growth of not only K562 cells but also these 2 variants. This might be because of the augmented inhibition of Erk1/2 phosphorylation. The new Abl kinase inhibitor nilotinib was 10-fold more potent than IM in inhibiting the growth of K562 cells. Nilotinib inhibited the growth of IM-R1 and IM-R2 cells as potently as K562 cells. The combination of nilotinib with CGP76030 showed little additivity, because the potency of nilotinib masked the efficacy of CGP76030. The new dual Abl/Lyn inhibitor INNO-406 (formerly NS-187) was slightly more potent than nilotinib in inhibiting the growth of all 3 cell lines. Because BCR-ABL gene amplification occurs in blast crisis, these inhibitors might overcome IM resistance in such patients' leukemia. (c) 2008 Wiley-Liss, Inc.

Gas phase UV and IR absorption spectra of CxF2x+1CHO (x=1-4)

DEFF Research Database (Denmark)

Hashikawa, Y; Kawasaki, M; Waterland, RL

2004-01-01

The UV and IR spectra of CxF2x+1 CHO (x = 1-4) were investigated using computational and experimental techniques. CxF2x+1CHO (x = 1-4) have broad UV absorption features centered at 300-310 nm. The maximum absorption cross-section increases significantly and shifts slightly to the red with increased...

Thermotolerance and thermosensitization in CHO and R1H cells: a comparative study

International Nuclear Information System (INIS)

Dikomey, E.; Eickhoff, J.; Jung, H.

1984-01-01

In CHO and R1H cells thermotolerance was induced by a pre-incubation at 40 0 C, by an acute heat shock at 43 0 C followed by a time interval at 37 0 C, and during continuous heating at 42 0 C. Thermotolerance, which was tested at 43 0 , primarily causes an increase in D 0 of the heat-response curve. The degree of maximum thermotolerance was found to be generally more pronounced in CHO than in R1H cells, but the time interval at 37 0 C, as well as at 40 0 C, to reach this maximum level was the same in both cell lines. CHO and R1H cells could be sensitized to 40 0 C by a pre-treatment at 43 0 C. When compared for the same survival rate after pre-treatment at 43 0 C alone the degree of thermosensitization was about the same in both cell lines. In either cell line thermosensitization was found to be suppressed when cells were made thermotolerant by a previous incubation at 40 0 C for 16 hours. (author)

Kinetics of the Br2-CH3CHO Photochemical Chain Reaction

Science.gov (United States)

Nicovich, J. M.; Shackelford, C. J.; Wine, P. H.

1997-01-01

Time-resolved resonance fluorescence spectroscopy was employed in conjunction with laser flash photolysis of Br2 to study the kinetics of the two elementary steps in the photochemical chain reaction nBr2 + nCH3CHO + hv yields nCH3CBrO + nHBr. In the temperature range 255-400 K, the rate coefficient for the reaction Br((sup 2)P(sub 3/2)) + CH3CHO yields CH3CO + HBr is given by the Arrhenius expression k(sub 6)(T) = (1.51 +/- 0.20) x 10(exp -11) exp(-(364 +/- 41)/T)cu cm/(molecule.s). At 298 K, the reaction CH3CO + Br2 yields CH3CBrO + Br proceeds at a near gas kinetic rate, k(sub 7)(298 K) = (1.08 +/- 0.38) x 10(exp -10)cu cm/(molecule.s).

Identification of potential molecular markers of ionizing radiation-induced mutations at the hprt locus in CHO cells

International Nuclear Information System (INIS)

Schwartz, J.L.; Sun, J.; Porter, R.C.

1995-01-01

Using multiplex polymerase chain reaction-based exon deletion analysis, we have analyzed mutations at the hprt locus from independent CHO cell mutants isolated from untreated, 60 Co x-ray-, and 212 Bi-exposed CHO-K1 cello and its radiation-sensitive derivative, xrs-5. In the 71 spontaneous CHO-K1 mutants analyzed, 78% showed no change in exon number or size, 20% showed loss of 1-8 exons (partial deletion), and 3% showed loss of all nine hprt exons (total deletion). Exposure of CHO-K1 cells to 6 Gy of γ rays (10% survival) produced 45% of the 20 mutants analyzed showing partial deletion, and 30% showing total deletion. Exposure to an equitoxic dose of a radiation from 212 Bi, a 220 Rn daughter, resulted in a spectrum similar to the γ-ray spectrum in that more than 75% of the 49 mutants analyzed were deletions. The α-radiation, however, tended to produce larger intragenic deletions that γ radiation. Of the 87 spontaneous xrs-5 mutants analyzed for deletions 44% showed partial deletion, and 14% showed total deletion. Exposure to α radiation (10% survival) resulted in a deletion spectrum similar to that seen in CHO-K1 cells. Of the 49 mutants analyzed, 43% showed no change in exon number or size, 16% showed partial deletion, and 41% showed total deletion. While the defect in xrs-5 has a profound effect on spontaneous mutation spectra, it does not appear to affect α-induced mutation spectra

A yigP mutant strain is a small colony variant of E. coli and shows pleiotropic antibiotic resistance.

Science.gov (United States)

Xia, Hui; Tang, Qiongwei; Song, Jie; Ye, Jiang; Wu, Haizhen; Zhang, Huizhan

2017-12-01

Small colony variants (SCVs) are a commonly observed subpopulation of bacteria that have a small colony size and distinctive biochemical characteristics. SCVs are more resistant than the wild type to some antibiotics and usually cause persistent infections in the clinic. SCV studies have been very active during the past 2 decades, especially Staphylococcus aureus SCVs. However, fewer studies on Escherichia coli SCVs exist, so we studied an E. coli SCV during an experiment involving the deletion of the yigP locus. PCR and DNA sequencing revealed that the SCV was attributable to a defect in the yigP function. Furthermore, we investigated the antibiotic resistance profile of the E. coli SCV and it showed increased erythromycin, kanamycin, and d-cycloserine resistance, but collateral sensitivity to ampicillin, polymyxin, chloramphenicol, tetracycline, rifampin, and nalidixic acid. We tried to determine the association between yigP and the pleiotropic antibiotic resistance of the SCV by analyzing biofilm formation, cellular morphology, and coenzyme Q (Q 8 ) production. Our results indicated that impaired Q 8 biosynthesis was the primary factor that contributed to the increased resistance and collateral sensitivity of the SCV. This study offers a novel genetic basis for E. coli SCVs and an insight into the development of alternative antimicrobial strategies for clinical therapy.

Cadmium toxcity in the pregnant rat

International Nuclear Information System (INIS)

Martin, P.G.; Hitchcock, B.B.; King, J.F.

1978-01-01

Iron-deficient and normal pregnant rats were assigned to groups that either received a dose of cadmium (0.025, 0.050, or 0.100 mmole) plus 8 μCi of /sup 115m/Cd on day 18 of gestation or served as a nondosed group. Animals were either sacrificed 3 days after the dosing or allowed to litter (nondosed and 0.100 mmole cadmium groups only); pups and dams were sacrificed at 14 days of age. Viability of iron-deficient dams and fetuses and pups from iron-deficient dams was affected by the 0.100 mmole cadmium dose to a greater degree than was that in comparable normal animals. Although calculated amounts of cadmium deposited in the dam's liver, kidney, blood, tibia, and fetuses were greater in iron-deficient than in normal animals at all doses, differences were not significant except in the amount of cadmium accumulated in the placenta at the highest cadmium doses. Total deposition in the placentas/litter was similar for normal and iron-deficient groups at each dose level. The decreased viability may have been due to the dam's decreased food intake; blockage of nutrients, especially minerals, by cadmium--protein complexes in the placenta; or hormonal interruptions of pregnancy by steroid--cadmium complexes

Cadmium - a case of mistaken identity

Energy Technology Data Exchange (ETDEWEB)

Taylor, D

1984-05-01

New evidence is presented which describes the impact of cadmium in the environment. Cadmium is a persistent material, although its compounds may undergo a range of chemical changes in the environment. In soluble form cadmium and its compounds are toxic at relatively low concentrations to aquatic animals although their bioconcentrations in such animals is in general low, and there is no evidence of biomagnification. In insoluble form cadmium and its compounds are relatively non-toxic to aquatic animals and are unlikely to be bioconcentrated. As such, cadmium is similar to most other heavy metals. Recent studies indicate that cadmium is not implicated in Itai-Itai disease and does not appear to cause hypertension or cancer. In addition, the accepted critical level in the kidney may have been underestimated. Thus, the hazard to man appears to be considerably less than the original estimates. In view of these data, there seems little justification in treating cadmium in any way differently from the other metals and hence no reason for retaining it on the Black List of the international conventions. 19 references.

Structural, electrical and optical studies of SILAR deposited cadmium oxide thin films: Annealing effect

International Nuclear Information System (INIS)

Salunkhe, R.R.; Dhawale, D.S.; Gujar, T.P.; Lokhande, C.D.

2009-01-01

Successive ionic layer adsorption and reaction (SILAR) method has been successfully employed for the deposition of cadmium oxide (CdO) thin films. The films were annealed at 623 K for 2 h in an air and changes in the structural, electrical and optical properties were studied. From the X-ray diffraction patterns, it was found that after annealing, H 2 O vapors from as-deposited Cd(O 2 ) 0.88 (OH) 0.24 were removed and pure cubic cadmium oxide was obtained. The as-deposited film consists of nanocrystalline grains of average diameter about 20-30 nm with uniform coverage of the substrate surface, whereas for the annealed film randomly oriented morphology with slight increase in the crystallite size has been observed. The electrical resistivity showed the semiconducting nature with room temperature electrical resistivity decreased from 10 -2 to 10 -3 Ω cm after annealing. The decrease in the band gap energy from 3.3 to 2.7 eV was observed after the annealing

Health hazards of environmental cadmium pollution

Energy Technology Data Exchange (ETDEWEB)

Nordberg, G F

1974-01-01

Cadmium, a metal widely used in industrial processes, has been recognized to be a highly toxic and dangerous environmental pollutant. In this study the author describes the sources and occurrence of cadmium, and the intake by human beings. He states that present standards for daily intake do not allow sufficient safety margins. The fate and known effects of cadmium in human beings are summarized; some effects associated with cadmium are renal (kidney) damage, anemia, hypertension, and liver damage. Cadmium was identified as the main cause of the Itai-Itai disease in Japan, and epidemiological studies from various areas of Japan are presented. 64 references, 9 figures, 5 tables.

Resistant starch intake at breakfast affects postprandial responses in type 2 diabetics and enhances the glucose-dependent insulinotropic polypeptide--insulin relationship following a second meal.

Science.gov (United States)

MacNeil, Stacey; Rebry, Rachel M; Tetlow, Ian J; Emes, Michael J; McKeown, Bruce; Graham, Terry E

2013-12-01

Resistant starch (RS) consumption can modulate postprandial metabolic responses, but its effects on carbohydrate (CHO) handling in type 2 diabetics (T2D) are unclear. It was hypothesized that a bagel high in RS would improve glucose and insulin homeostasis following the 1st meal, regardless of the amount of available CHO, and that in association with incretins, the effects would carry over to a 2nd meal. Using a randomized crossover design, 12 T2D ingested four different bagel treatments (their 1st meal) determined by available CHO and the weight or amount of bagel consumed: treatment A, without RS (50 g of available CHO); treatment B, with RS (same total CHO as in A); treatment C, with RS (same available CHO as in A); and treatment D, with the same RS as in B and available CHO as in A and C. A standard 2nd meal was ingested 3 h later. Following the first meal, B elicited a lower glucose incremental area under the curve (iAUC) than C (P portion of the available CHO, while ingesting more RS influenced the GIP-insulin axis following the 2nd meal.

A potential food-grade cloning vector for Streptococcus thermophilus that uses cadmium resistance as the selectable marker.

Science.gov (United States)

Wong, Wing Yee; Su, Ping; Allison, Gwen E; Liu, Chun-Qiang; Dunn, Noel W

2003-10-01

A potential food-grade cloning vector, pND919, was constructed and transformed into S. thermophilus ST3-1, a plasmid-free strain. The vector contains DNAs from two different food-approved organisms, Streptococcus thermophilus and Lactococcus lactis. The 5.0-kb pND919 is a derivative of the cloning vector pND918 (9.3 kb) and was constructed by deletion of the 4.3-kb region of pND918 which contained DNA from non-food-approved organisms. pND919 carries a heterologous native cadmium resistance selectable marker from L. lactis M71 and expresses the Cd(r) phenotype in S. thermophilus transformants. With the S. thermophilus replicon derived from the shuttle vector pND913, pND919 is able to replicate in the two S. thermophilus industrial strains tested, ST3-1 and ST4-1. Its relatively high retention rate in S. thermophilus further indicates its usefulness as a potential food-grade cloning vector. To our knowledge, this is the first report of a replicative potential food-grade vector for the industrially important organism S. thermophilus.

Cadmium removal by Lemna minor and Spirodela polyrhiza.

Science.gov (United States)

Chaudhuri, Devaleena; Majumder, Arunabha; Misra, Amal K; Bandyopadhyay, Kaushik

2014-01-01

The present study investigates the ability of two genus of duckweed (Lemna minor and Spirodela polyrhiza) to phytoremediate cadmium from aqueous solution. Duckweed was exposed to six different cadmium concentrations, such as, 0.5,1.0,1.5, 2.0, 2.5, and 3.0 mg/L and the experiment was continued for 22 days. Water samples were collected periodically for estimation of residual cadmium content in aqueous solution. At the end of treatment period plant samples were collected and accumulated cadmium content was measured. Cadmium toxicity was observed through relative growth factor and changes in chlorophyll content Experimental results showed that Lemna minor and Spirodela polyrhiza were capable of removing 42-78% and 52-75% cadmium from media depending upon initial cadmium concentrations. Cadmium was removed following pseudo second order kinetic model Maximum cadmium accumulation in Lemna minor was 4734.56 mg/kg at 2 mg/L initial cadmium concentration and 7711.00 mg/kg in Spirodela polyrhiza at 3 mg/L initial cadmium concentration at the end of treatment period. Conversely in both cases maximum bioconcentration factor obtained at lowest initial cadmium concentrations, i.e., 0.5 mg/L, were 3295.61 and 4752.00 for Lemna minor and Spirodela polyrhiza respectively. The present study revealed that both Lemna minor and Spirodela polyrhiza was potential cadmium accumulator.

Cadmium Exposure is Associated with the Prevalence of Dyslipidemia

Directory of Open Access Journals (Sweden)

Zhou Zhou

2016-11-01

Full Text Available Background: Cadmium is a widespread environmental and occupational pollutant that accumulates in human body with a biological half-life exceeding 10 years. Cadmium exposure has been demonstrated to increase rates of cardiovascular diseases. Whether occupational cadmium exposure is associated with the increase in the prevalence of dyslipidemia and hence contributes to the risk of cardiovascular diseases is still equivocal. To test the hypothesis that exposure to cadmium is related to the prevalence of dyslipidemia, we examined the associations between blood cadmium concentration and the prevalence of dyslipidemia in workers occupationally exposed to cadmium in China. Methods: A cross-sectional survey on demographic data, blood cadmium level and lipid profile in cadmium exposed workers from seven cadmium smelting factories in central and southwestern China was conducted. We measured blood cadmium concentration and lipid components of 1489 cadmium exposed workers. The prevalence of dyslipidemia was compared across blood cadmium quartiles. Associations between the blood cadmium concentrations and the prevalence of dyslipidemia were assessed using confounder adjusted linear and logistic regressions. Results: The blood cadmium concentration was 3.61±0.84µg/L ( mean ±SD. The prevalence of dyslipidemia in this occupational population was 66.3%. Mean blood cadmium concentration of workers with dyslipedemia was significantly higher than that of workers without dyslipidemia (p Conclusion: Elevated blood cadmium concentration is associated with prevalence of dyslipidemia. Cadmium exposure could alter lipid metabolism in humans. It is imperative to control cadmium exposure of occupational population in cadmium related industries and reduce adverse health effects.

Defect control in room temperature deposited cadmium sulfide thin films by pulsed laser deposition

International Nuclear Information System (INIS)

Hernandez-Como, N.; Martinez-Landeros, V.; Mejia, I.; Aguirre-Tostado, F.S.; Nascimento, C.D.; Azevedo, G. de M; Krug, C.; Quevedo-Lopez, M.A.

2014-01-01

The control of defects in cadmium sulfide thin films and its impact on the resulting CdS optical and electrical characteristics are studied. Sulfur vacancies and cadmium interstitial concentrations in the CdS films are controlled using the ambient pressure during pulsed laser deposition. CdS film resistivities ranging from 10 −1 to 10 4 Ω-cm are achieved. Hall Effect measurements show that the carrier concentration ranges from 10 19 to 10 13 cm −3 and is responsible for the observed resistivity variation. Hall mobility varies from 2 to 12 cm 2 /V-s for the same pressure regime. Although the energy bandgap remains unaffected (∼ 2.42 eV), the optical transmittance is reduced due to the increase of defects in the CdS films. Rutherford back scattering spectroscopy shows the dependence of the CdS films stoichiometry with deposition pressure. The presence of CdS defects is attributed to more energetic species reaching the substrate, inducing surface damage in the CdS films during pulsed laser deposition. - Highlights: • CdS thin films deposited by pulsed laser deposition at room temperature. • The optical, electrical and structural properties were evaluated. • Carrier concentration ranged from 10 19 to 10 13 cm −3 . • The chemical composition was studied by Rutherford back scattering. • The density of sulfur vacancies and cadmium interstitial was varied

Glycoprofiling effects of media additives on IgG produced by CHO cells in fed-batch bioreactors

DEFF Research Database (Denmark)

Kildegaard, Helene Faustrup; Fan, Yuzhou; Wagtberg Sen, Jette

2016-01-01

Therapeutic monoclonal antibodies (mAbs) are mainly produced by heterogonous expression in Chinese hamster ovary (CHO) cells. The glycosylation profile of the mAbs has major impact on the efficacy and safety of the drug and is therefore an important parameter to control during production. In this......Therapeutic monoclonal antibodies (mAbs) are mainly produced by heterogonous expression in Chinese hamster ovary (CHO) cells. The glycosylation profile of the mAbs has major impact on the efficacy and safety of the drug and is therefore an important parameter to control during production....... In this study, the effect on IgG N-glycosylation from feeding CHO cells with eight glycosylation precursors during cultivation was investigated. The study was conducted in fed-batch mode in bioreactors with biological replicates to obtain highly controlled and comparable conditions. We assessed charge...

Metal resistance sequences and transgenic plants

Science.gov (United States)

Meagher, Richard Brian; Summers, Anne O.; Rugh, Clayton L.

1999-10-12

The present invention provides nucleic acid sequences encoding a metal ion resistance protein, which are expressible in plant cells. The metal resistance protein provides for the enzymatic reduction of metal ions including but not limited to divalent Cu, divalent mercury, trivalent gold, divalent cadmium, lead ions and monovalent silver ions. Transgenic plants which express these coding sequences exhibit increased resistance to metal ions in the environment as compared with plants which have not been so genetically modified. Transgenic plants with improved resistance to organometals including alkylmercury compounds, among others, are provided by the further inclusion of plant-expressible organometal lyase coding sequences, as specifically exemplified by the plant-expressible merB coding sequence. Furthermore, these transgenic plants which have been genetically modified to express the metal resistance coding sequences of the present invention can participate in the bioremediation of metal contamination via the enzymatic reduction of metal ions. Transgenic plants resistant to organometals can further mediate remediation of organic metal compounds, for example, alkylmetal compounds including but not limited to methyl mercury, methyl lead compounds, methyl cadmium and methyl arsenic compounds, in the environment by causing the freeing of mercuric or other metal ions and the reduction of the ionic mercury or other metal ions to the less toxic elemental mercury or other metals.

Antimicrobial drug resistance in Staphylococcus aureus isolated from cattle in Brazil.

Science.gov (United States)

Pereira, M S; Siqueira-Júnior, J P

1995-06-01

Isolates of Staphylococcus aureus obtained from apparently healthy cattle in the State of Paraiba, Brazil were characterized in relation to resistance to 21 antimicrobial agents. Among the 46 isolates obtained, resistance to penicillin was most frequent, followed by resistance to cadmium, streptomycin, arsenate, tetracycline, mercury, erythromycin and kanamycin/neomycin. All isolates were susceptible to fusidic acid, ethidium bromide, cetrimide, chloramphenicol, benzalkonium chloride, doxycycline, gentamicin, methicillin, minocycline, novobiocin, rifamycin, tylosin and vancomycin. Only six isolates were susceptible to all the drugs tested. With respect to the antibiotics, multi-resistant isolates were uncommon. These results are probably a consequence of the peculiarities of local drug usage pressures. In relation to metal ions, resistance to mercury was rare while resistance to arsenate was relatively frequent, which contrasts with the situation for human Staph. aureus strains. After treatment with ethidium bromide, elimination of resistance to penicillin, tetracycline, streptomycin, erythromycin and cadmium was observed, which was consistent with the genetic determinants being plasmid-borne.

Cadmium Exposure is Associated with the Prevalence of Dyslipidemia.

Science.gov (United States)

Zhou, Zhou; Lu, Yong-Hui; Pi, Hui-Feng; Gao, Peng; Li, Min; Zhang, Lei; Pei, Li-Ping; Mei, Xiang; Liu, Lin; Zhao, Qi; Qin, Qi-Zhong; Chen, Yu; Jiang, Yue-Ming; Zhang, Zhao-Hui; Yu, Zheng-Ping

2016-01-01

Cadmium is a widespread environmental and occupational pollutant that accumulates in human body with a biological half-life exceeding 10 years. Cadmium exposure has been demonstrated to increase rates of cardiovascular diseases. Whether occupational cadmium exposure is associated with the increase in the prevalence of dyslipidemia and hence contributes to the risk of cardiovascular diseases is still equivocal. To test the hypothesis that exposure to cadmium is related to the prevalence of dyslipidemia, we examined the associations between blood cadmium concentration and the prevalence of dyslipidemia in workers occupationally exposed to cadmium in China. A cross-sectional survey on demographic data, blood cadmium level and lipid profile in cadmium exposed workers from seven cadmium smelting factories in central and southwestern China was conducted. We measured blood cadmium concentration and lipid components of 1489 cadmium exposed workers. The prevalence of dyslipidemia was compared across blood cadmium quartiles. Associations between the blood cadmium concentrations and the prevalence of dyslipidemia were assessed using confounder adjusted linear and logistic regressions. The blood cadmium concentration was 3.61±0.84µg/L ( mean ±SD). The prevalence of dyslipidemia in this occupational population was 66.3%. Mean blood cadmium concentration of workers with dyslipedemia was significantly higher than that of workers without dyslipidemia (p dyslipidemia increased dose-dependently with elevations in blood cadmium concentrations (p for trend dyslipidemia across the increasing blood cadmium quartiles were 1.21(1.16-1.55), 1.56(1.11-1.87), 1.79(1.26-2.25) respectively (referencing to 1.00; p for trend dyslipidemia remained unchanged (all p for trend dyslipidemia. Cadmium exposure could alter lipid metabolism in humans. It is imperative to control cadmium exposure of occupational population in cadmium related industries and reduce adverse health effects. © 2016 The

Noninvasive Detection of AR-FL/AR-V7 as a Predictive Biomarker for Therapeutic Resistance in Men with Metastatic Castration-Resistant Prostate Cancer

Science.gov (United States)

2017-10-01

acknowledged federal support) 5. Antonarakis ES, Armstrong AJ, Dehm SM, Luo J. Androgen receptor variant-driven prostate cancer : clinical implications...Resistant Prostate Cancer abstract Purpose A splice variant of the androgen receptor , AR-V7, confers resistance to AR-targeted therapies (ATTs) but not...androgen receptor ; AR-V7, androgen receptor splice variant 7; mCRPC, metastatic castration-resistant prostate cancer ; n/N, number of patients in that

Electromagnetic field pretreatment of Sinapis alba seeds improved cadmium phytoextraction.

Science.gov (United States)

Bulak, Piotr; Lata, Lesia; Plak, Andrzej; Wiącek, Dariusz; Strobel, Wacław; Walkiewicz, Anna; Pietruszewski, Stanisław; Bieganowski, Andrzej

2018-03-21

It was hypothesized that electromagnetic field (EMF) pretreatment of white mustard (Sinapis alba L.) seeds could increase the accumulation of non-essential, pollutant heavy metals such as cadmium (Cd) in shoots. Seeds of white mustard were treated with either 60 or 120 mT of alternating EMF (50 Hz) for 1 minute and then grown in a Petri dish in the presence of Cd, in comparison to the control (seeds grown without EMF pretreatment). Biomass production and content of calcium (Ca) and Cd in seedling shoots were measured. The Cd content in shoots from the EMF-treated seeds was higher in both variants than in the control (by 73% and 78%, respectively; p phytoextraction, but more research is needed.

Reviews of the environmental effects of pollutants: IV. Cadmium

International Nuclear Information System (INIS)

Hammons, A.S.; Huff, J.E.; Braunstein, H.M.; Drury, J.S.; Shriner, C.R.; Lewis, E.B.; Whitfield, B.L.; Towill, L.E.

1978-06-01

This report is a comprehensive, multidisciplinary review of the health and environmental effects of cadmium and specific cadmium derivatives. More than 500 references are cited. The cadmium body burden in animals and humans results mainly from the diet. In the United States, the normal intake of cadmium for adult humans is estimated at about 50 μg per day. Tobacco smoke is a significant additional source of cadmium exposure. The kidneys and liver together contain about 50% of the total cadmium body burden. Acute cadmium poisoning is primarily an occupational problem, generally from inhalation of cadmium fumes or dusts. In the general population, incidents of acute poisoning by inhaled or ingested cadmium or its compounds are relatively rare. The kidney is the primary target organ for toxicity from prolonged low-level exposure to cadmium. No causal relationship has been established between cadmium exposure and human cancer, although a possible link between cadmium and prostate cancer has been indicated. Cadmium has been shown to be teratogenic in rats, hamsters, and mice, but no such effects have been proven in humans. Cadmium has been reported to increase the frequency of chromosomal aberrations in cultured Chinese hamster ovary cells and in human peripheral leukocytes. The major concern about environmental cadmium is the potential effects on the general population. There is no substantial evidence of hazard from current levels of cadmium in air, water, or food. However, because cadmium is a cumulative poison and because present intake provides a relatively small safety margin, there are adequate reasons for concern over possible future increases in background levels

Reviews of the environmental effects of pollutants: IV. Cadmium

Energy Technology Data Exchange (ETDEWEB)

Hammons, A.S.; Huff, J.E.; Braunstein, H.M.; Drury, J.S.; Shriner, C.R.; Lewis, E.B.; Whitfield, B.L.; Towill, L.E.

1978-06-01

This report is a comprehensive, multidisciplinary review of the health and environmental effects of cadmium and specific cadmium derivatives. More than 500 references are cited. The cadmium body burden in animals and humans results mainly from the diet. In the United States, the normal intake of cadmium for adult humans is estimated at about 50 ..mu..g per day. Tobacco smoke is a significant additional source of cadmium exposure. The kidneys and liver together contain about 50% of the total cadmium body burden. Acute cadmium poisoning is primarily an occupational problem, generally from inhalation of cadmium fumes or dusts. In the general population, incidents of acute poisoning by inhaled or ingested cadmium or its compounds are relatively rare. The kidney is the primary target organ for toxicity from prolonged low-level exposure to cadmium. No causal relationship has been established between cadmium exposure and human cancer, although a possible link between cadmium and prostate cancer has been indicated. Cadmium has been shown to be teratogenic in rats, hamsters, and mice, but no such effects have been proven in humans. Cadmium has been reported to increase the frequency of chromosomal aberrations in cultured Chinese hamster ovary cells and in human peripheral leukocytes. The major concern about environmental cadmium is the potential effects on the general population. There is no substantial evidence of hazard from current levels of cadmium in air, water, or food. However, because cadmium is a cumulative poison and because present intake provides a relatively small safety margin, there are adequate reasons for concern over possible future increases in background levels.

Cadmium-induced fetal toxicity in the rat

International Nuclear Information System (INIS)

Levin, A.A.

1980-01-01

Cadmium, a heavy metal environment contaminant, induces fetal death and placental necrosis in the Wistar rat. This study investigated fetal, maternal, and placental responses to cadmium intoxication. Subcutaneous injection of CdCl 2 to dams on day 18 of pregnancy produced a high incidence of fetal death (75%) and placental necrosis. Death in the fetus was produced despite limited fetal accumulations of cadmium. Distribution studies using 109 Cd-labeled CdCl 2 demonstrated that less than 0.1% of the injected dose was associated with the fetus. To determine if fetuses were sensitive to these low levels of cadmium, direct injections of CdCl 2 into fetuses were performed in utero. Direct injections produced fetal accumulations 8-fold greater than those following maternal injections. The 8-fold greater fetal accumulations following direct injection were associated with only a 12% fetal mortality compared to the 75% mortality following maternal injections. The data indicated that the fetal toxicity of cadmium following maternal injections was not the result of direct effects of cadmium on the fetus. In conclusion, cadmium-induced fetal death was not the result of direct effects of cadmium on the fetus but may have been induced by placental cellular injury resulting from high accumulations of cadmium in the placenta. A vascular response to placental injury, leading to decreased utero-placental bood flow and cadmium-induced alterations in trophoblastic function, resulted in fetal death

Cadmium in Salix. A study to show the capacity of Salix to remove cadmium from farmland

International Nuclear Information System (INIS)

Oestman, G.

1994-01-01

The aim of this report has been to show the ability of Salix to take up cadmium and how the uptake varies between different types of soil. The information that the results are based on has been obtained from analyses of soil and Salix. The samples were taken at five sites in the district around Lake Maelaren. Two or three stands were taken at each place. The factors studied were the pH, the organic matter content, and the concentration of cadmium in the soil. Salix has a good ability, relative to other crops, to remove cadmium from arable land. The cadmium uptake is 35 times higher with Salix than with straw or energy grass. Salix uptake of cadmium varies between 3 and 14% of the cadmium content in the soil that is accessible to plants. The present annual increase of cadmium in arable land is 1 g/ha, whereas the removal in a Salix plantation is 21 g Cd/ha, yr at an annual growth of 10 tonnes DM. If the Cd uptake is the same each year, then a total of 420 g Cd/ha is removed when Salix is grown over a 20-year period. This is a very large part of the topsoil's total cadmium content, which is 550 g/ha on average in Sweden. The investigation reveals no clear relationship between the Cd concentration in Salix and the concentration of Cd in the soil, the organic matter content or the pH. 22 refs, 4 figs, 2 tabs

Use of cadmium in solution in the EL 4 reactor moderator irreversible fixing of cadmium on the metallic surfaces; Utilisation du cadmium en solution dans le moderateur du reacteur EL 4 - fixation irreversible du cadmium sur les surfaces metalliques

Energy Technology Data Exchange (ETDEWEB)

Croix, O; Paoli, O; Lecomte, J; Dolle, L; Gallic, Y [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1964-07-01

In the framework of research into the poisoning of the EL-4 reactor by cadmium sulphate, measurements have been made by two different methods of the residual amounts of cadmium liable to be fixed irreversibly on the surfaces in contact with the heavy water. A marked influence of the pH has been noticed. The mechanism of the irreversible fixing is compatible with the hypothesis of an ion-exchange in the surface oxide layer. In a sufficiently wide range of pH the cadmium thus fixed causes very little residual poisoning. The stability of the cadmium sulphate solutions is however rather low in the conditions of poisoning. (authors) [French] Dans le cadre des etudes sur l'empoisonnement du reacteur EL-4 par le sulfate de cadmium, les quantites residuelles de cadmium susceptibles de se fixer irreversiblement sur les parois que mouillerait l'eau lourde, ont ete mesurees experimentalement par deux methodes differentes. On observe une influence nette du pH. Le mecanisme de la fixation irreversible est compatible avec l'hypothese d'un echange d'ions dans la pellicule d'oxyde superficielle. Dans des limites suffisamment larges de pH, la cadmium ainsi fixe n'occasionne pas d'empoisonnement residuel important. La stabilite des solutions de sulfate de cadmium dans les conditions de l'empoisonnement est cependant mediocre. (auteurs)

Cadmium incorporation by the marine copepod Pseudodiaptomus coronatus

International Nuclear Information System (INIS)

Sick, L.V.; Baptist, G.J.

1979-01-01

Pseudodiaptomus coronatus, after exposure to phytoplankton and cadmium in concentrations like those in temperate, coastal environments, incorporated 109 Cd at higher rates from ambient water than from phytoplankton food. When ambient stable cadmium concentrations were increased from 0.03 to 1.00 μg.liter -1 , cadmium concentration by phytoplankton cells increased and the rate of cell ingestion by P. coronatus decreased. This inverse relation between the accumulation of cadmium in phytoplankton cells and the animal's ingestion rate resulted in relatively small net increases in the cadmium accumulated from phytoplankton by copepods. Rates of stable cadmium ingestion for P. coronatus ranged from 0.18 to 0.38 ng.mg animal dry wt -1 .h -1 , depending on the initial algal cell density and the ambient cadmium concentration. For cadmium concentrations of 0.03 to 1.00 μg.liter -1 , percentage assimilation efficiencies ranged from 13.20 to 68.40. Both rates of cadmium ingestion and assimilation efficiencies were higher than published values for carnivorous zooplankton

Monitoring of BHT-quinone and BHT-CHO in the gas of capsules of Asclepias physocarpa.

Science.gov (United States)

Ma, Bing-Ji; Peng, Hua; Liu, Ji-Kai

2006-01-01

Three volatile components, namely benzoic acid ethyl ester (1), 2,6-di-tert-butyl-p-benzoquinone (BHT-quinone) (2), and 3,5-di-tert-butyl-4-hydroxybenzaldehyde (BHT-CHO) (3), were detected from the gas in the capsules of Asclepias physocarpa by means of GC/MS analysis. BHT-quinone and BHT-CHO as organic pollutants are the degradation products of the antioxidant 2,6-di-tert-butyl-4-methylphenol (BHT). Ground water, lake water and/or rain water are a source of BHT metabolites in the plant Asclepias physocarpa.

Structure and properties of YBa2Cu3O7-δ superconductor doped with bulk cadmium oxide

Directory of Open Access Journals (Sweden)

A Echresh

2010-09-01

Full Text Available In this paper, the Y1-xCdxBa2Cu3O7-δ superconductor with x=0, 0.05, 0.1, 0.15, 0.2, 0.3, 0.4, 0.5 are prepared using the solid state method and the structure, electrical resistance, critical current density and critical temperature of it, have been studied. The results show that these doping do not affect so much on the structure and lattice parameters. The electrical resistance of samples increased with doping. A little amount of doping cadmium improve critical current density such that the sample x=0.1 has a maximum critical current density among the samples. The critical temperature with doping cadmium up to x=0.2 has little fluctuation and its variation can be ignored, but by increasing up to x=0.5 the critical temperature decreases gradually.

Whey Protein Supplementation Enhances Whole Body Protein Metabolism and Performance Recovery after Resistance Exercise: A Double-Blind Crossover Study.

Science.gov (United States)

West, Daniel W D; Abou Sawan, Sidney; Mazzulla, Michael; Williamson, Eric; Moore, Daniel R

2017-07-11

No study has concurrently measured changes in free-living whole body protein metabolism and exercise performance during recovery from an acute bout of resistance exercise. We aimed to determine if whey protein ingestion enhances whole body net protein balance and recovery of exercise performance during overnight (10 h) and 24 h recovery after whole body resistance exercise in trained men. In a double-blind crossover design, 12 trained men (76 ± 8 kg, 24 ± 4 years old, 14% ± 5% body fat; means ± standard deviation (SD)) performed resistance exercise in the evening prior to consuming either 25 g of whey protein (PRO; MuscleTech 100% Whey) or an energy-matched placebo (CHO) immediately post-exercise (0 h), and again the following morning (~10 h of recovery). A third randomized trial, completed by the same participants, involving no exercise and no supplement served as a rested control trial (Rest). Participants ingested [ 15 N]glycine to determine whole body protein kinetics and net protein balance over 10 and 24 h of recovery. Performance was assessed pre-exercise and at 0, 10, and 24 h of recovery using a battery of tests. Net protein balance tended to improve in PRO ( P = 0.064; effect size (ES) = 0.61, PRO vs. CHO) during overnight recovery. Over 24 h, net balance was enhanced in PRO ( P = 0.036) but not in CHO ( P = 0.84; ES = 0.69, PRO vs. CHO), which was mediated primarily by a reduction in protein breakdown (PRO protein supplementation improved MVC (ES = 0.76), REP (ES = 0.44), and peak power (ES = 0.55). In conclusion, whey protein supplementation enhances whole body anabolism, and may improve acute recovery of exercise performance after a strenuous bout of resistance exercise.

A global RNA-seq-driven analysis of CHO host and production cell lines reveals distinct differential expression patterns of genes contributing to recombinant antibody glycosylation.

Science.gov (United States)

Könitzer, Jennifer D; Müller, Markus M; Leparc, Germán; Pauers, Martin; Bechmann, Jan; Schulz, Patrick; Schaub, Jochen; Enenkel, Barbara; Hildebrandt, Tobias; Hampel, Martin; Tolstrup, Anne B

2015-09-01

Boehringer Ingelheim uses two CHO-DG44 lines for manufacturing biotherapeutics, BI-HEX-1 and BI-HEX-2, which produce distinct cell type-specific antibody glycosylation patterns. A recently established CHO-K1 descended host, BI-HEX-K1, generates antibodies with glycosylation profiles differing from CHO-DG44. Manufacturing process development is significantly influenced by these unique profiles. To investigate the underlying glycosylation related gene expression, we leveraged our CHO host and production cell RNA-seqtranscriptomics and product quality database together with the CHO-K1 genome. We observed that each BI-HEX host and antibody producing cell line has a unique gene expression fingerprint. CHO-DG44 cells only transcribe Fut10, Gfpt2 and ST8Sia6 when expressing antibodies. BI-HEX-K1 cells express ST8Sia6 at host cell level. We detected a link between BI-HEX-1/BI-HEX-2 antibody galactosylation and mannosylation and the gene expression of the B4galt gene family and genes controlling mannose processing. Furthermore, we found major differences between the CHO-DG44 and CHO-K1 lineages in the expression of sialyl transferases and enzymes synthesizing sialic acid precursors, providing a rationale for the lack of immunogenic NeuGc/NGNA synthesis in CHO. Our study highlights the value of systems biotechnology to understand glycoprotein synthesis and product glycoprofiles. Such data improve future production clone selection and process development strategies for better steering of biotherapeutic product quality. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An association between urinary cadmium and urinary stone disease in persons living in cadmium-contaminated villages in northwestern Thailand: A population study

International Nuclear Information System (INIS)

Swaddiwudhipong, Witaya; Mahasakpan, Pranee; Limpatanachote, Pisit; Krintratun, Somyot

2011-01-01

Excessive urinary calcium excretion is the major risk of urinary stone formation. Very few population studies have been performed to determine the relationship between environmental cadmium exposure and urinary stone disease. This population-based study examined an association between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and prevalence of urinary stones in persons aged 15 years and older, who lived in the 12 cadmium-contaminated villages in the Mae Sot District, Tak Province, northwestern Thailand. A total of 6748 persons were interviewed and screened for urinary cadmium and urinary stone disease in 2009. To test a correlation between urinary excretion of cadmium and calcium, we measured urinary calcium content in 1492 persons, who lived in 3 villages randomly selected from the 12 contaminated villages. The rate of urinary stones significantly increased from 4.3% among persons in the lowest quartile of urinary cadmium to 11.3% in the highest quartile. An increase in stone prevalence with increasing urinary cadmium levels was similarly observed in both genders. Multiple logistic regression analysis revealed a positive association between urinary cadmium levels and stone prevalence, after adjusting for other co-variables. The urinary calcium excretion significantly increased with increasing urinary cadmium levels in both genders, after adjusting for other co-variables. Elevated calciuria induced by cadmium might increase the risk of urinary stone formation in this environmentally exposed population. - Research highlights: → Excessive calciuria is the major risk of urinary stone formation. → We examine cadmium-exposed persons for urinary cadmium, calcium, and stones. → The rate of urinary stones increases with increasing urinary cadmium. → Urinary calcium excretion increases with increasing urinary cadmium. → Elevated calciuria induced by cadmium may increase the risk of urinary stones.

The fatty acid profile of rainbow trout liver cells modulates their tolerance to methylmercury and cadmium

International Nuclear Information System (INIS)

Ferain, Aline; Bonnineau, Chloé; Neefs, Ineke; Rees, Jean François; Larondelle, Yvan; Schamphelaere, Karel A.C.De; Debier, Cathy

2016-01-01

Highlights: • The phospholipid composition of rainbow trout liver cells was successfully changed. • Cell phospholipids influenced methylmercury (MeHg) and cadmium (Cd) toxicity. • Cells enriched in 18:3n-3, 20:5n-3 or 22:5n-6 were more resistant to MeHg and Cd. • Cell enrichment in 22:6n-3 increased resistance to Cd but not MeHg. - Abstract: The polyunsaturated fatty acid (PUFA) composition of fish tissues, which generally reflects that of the diet, affects various cellular properties such as membrane structure and fluidity, energy metabolism and susceptibility to oxidative stress. Since these cellular parameters can play an important role in the cellular response to organic and inorganic pollutants, a variation of the PUFA supply might modify the toxicity induced by such xenobiotics. In this work, we investigated whether the cellular fatty acid profile has an impact on the in vitro cell sensitivity to two environmental pollutants: methylmercury and cadmium. Firstly, the fatty acid composition of the rainbow trout liver cell line RTL-W1 was modified by enriching the growth medium with either alpha-linolenic acid (ALA, 18:3n-3), eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), linoleic acid (LA, 18:2n-6), arachidonic acid (AA, 20:4n-6) or docosapentaenoic acid (DPA, 22:5n-6). These modified cells and their control (no PUFA enrichment) were then challenged for 24 h with increasing concentrations of methylmercury or cadmium. We observed that (i) the phospholipid composition of the RTL-W1 cells was profoundly modulated by changing the PUFA content of the growth medium: major modifications were a high incorporation of the supplemented PUFA in the cellular phospholipids, the appearance of direct elongation and desaturation metabolites in the cellular phospholipids as well as a change in the gross phospholipid composition (PUFA and monounsaturated fatty acid (MUFA) levels and n-3/n-6 ratio); (ii) ALA, EPA and DPA enrichment significantly

The fatty acid profile of rainbow trout liver cells modulates their tolerance to methylmercury and cadmium

Energy Technology Data Exchange (ETDEWEB)

Ferain, Aline, E-mail: aline.ferain@uclouvain.be [Institute of Life Sciences, Université catholique de Louvain, Place Croix du Sud 2/L7.05.08, B-1348 Louvain-la-Neuve (Belgium); Bonnineau, Chloé [Institute of Life Sciences, Université catholique de Louvain, Place Croix du Sud 2/L7.05.08, B-1348 Louvain-la-Neuve (Belgium); Irstea, UR MALY, Centre de Lyon-Villeurbanne, rue de la Doua 5/32108, F-69616 Villeurbanne (France); Neefs, Ineke; Rees, Jean François; Larondelle, Yvan [Institute of Life Sciences, Université catholique de Louvain, Place Croix du Sud 2/L7.05.08, B-1348 Louvain-la-Neuve (Belgium); Schamphelaere, Karel A.C.De [Laboratory of Environmental Toxicology and Aquatic Ecology, Environmental Toxicology Unit, Ghent University, J. Plateaustraat 22, B-9000 Ghent (Belgium); Debier, Cathy [Institute of Life Sciences, Université catholique de Louvain, Place Croix du Sud 2/L7.05.08, B-1348 Louvain-la-Neuve (Belgium)

2016-08-15

Highlights: • The phospholipid composition of rainbow trout liver cells was successfully changed. • Cell phospholipids influenced methylmercury (MeHg) and cadmium (Cd) toxicity. • Cells enriched in 18:3n-3, 20:5n-3 or 22:5n-6 were more resistant to MeHg and Cd. • Cell enrichment in 22:6n-3 increased resistance to Cd but not MeHg. - Abstract: The polyunsaturated fatty acid (PUFA) composition of fish tissues, which generally reflects that of the diet, affects various cellular properties such as membrane structure and fluidity, energy metabolism and susceptibility to oxidative stress. Since these cellular parameters can play an important role in the cellular response to organic and inorganic pollutants, a variation of the PUFA supply might modify the toxicity induced by such xenobiotics. In this work, we investigated whether the cellular fatty acid profile has an impact on the in vitro cell sensitivity to two environmental pollutants: methylmercury and cadmium. Firstly, the fatty acid composition of the rainbow trout liver cell line RTL-W1 was modified by enriching the growth medium with either alpha-linolenic acid (ALA, 18:3n-3), eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), linoleic acid (LA, 18:2n-6), arachidonic acid (AA, 20:4n-6) or docosapentaenoic acid (DPA, 22:5n-6). These modified cells and their control (no PUFA enrichment) were then challenged for 24 h with increasing concentrations of methylmercury or cadmium. We observed that (i) the phospholipid composition of the RTL-W1 cells was profoundly modulated by changing the PUFA content of the growth medium: major modifications were a high incorporation of the supplemented PUFA in the cellular phospholipids, the appearance of direct elongation and desaturation metabolites in the cellular phospholipids as well as a change in the gross phospholipid composition (PUFA and monounsaturated fatty acid (MUFA) levels and n-3/n-6 ratio); (ii) ALA, EPA and DPA enrichment significantly

PROTEINS OF POTATOES IN RELATION TO THE CONTENT OF CADMIUM IN THEIR TUBERS

Directory of Open Access Journals (Sweden)

Judita Bystrická

2010-11-01

Full Text Available In the work the influence of cadmium in soil on the range of cumulating in tubers of potatoes and in proteins of potatoes grown under model conditions of pot trial experiment and under the real conditions of locality Imeľ in Danube Lowland was surveyed. Under conditions of pot trial the increased contents in tubers positively correlated with contents of cadmium applied into soil; the highest content of Cd was assessed in variety Junior (from 0.211 mg.kg-1 FM in 1st variant to 0.715 mg.kg-1 FM in 4th variant. The influence of increased content of Cd was manifested statistically significant in the content of proteins also in the content of Cd in protein fractions (1st var. 0.026 (Asterix – 0.045 (Agria mg.kg-1 FM; 2nd var. 0.047 (Livera – 0.085 (Asterix mg.kg-1 FM; 3rd var. 0.06 (Livera – 0.117 (Junior mg.kg-1 FM; 4th var. 0.068 (Livera – 0.142 (Asterix mg.kg-1 FM. Contents of Cd in potatoes from locality Imeľ did not exceed the value 0.1 mg.kg-1 FM defined in PK SR. The average contents of proteins were in range from 1.19 % (Victoria to 1.489 % (Adora, the average content of Cd cumulated in proteins was the highest in variety Vivaldi (1.317 μg.kg-1 FM. Positive correlation was confirmed between the content of Cd in potato tubers and in proteins only in Livera variety. doi:10.5219/74

A Novel Nonsense Variant in Nav1.5 Cofactor MOG1 Eliminates Its Sodium Current Increasing Effect and May Increase the Risk of Arrhythmias

DEFF Research Database (Denmark)

Olesen, Morten S; Jensen, Niels F; Holst, Anders G

2011-01-01

at a lower frequency (1.8% vs 0.4%, P = 0.078). Electrophysiological investigation showed that the p.E61X variant completely eliminates the sodium current-increasing effect of MOG1 and thereby causes loss of function in the sodium current. When mimicking heterozygosity by coexpression of Nav1.5 with wild......BACKGROUND: The protein MOG1 is a cofactor of the cardiac sodium channel, Nav1.5. Overexpression of MOG1 in Nav1.5-expressing cells increases sodium current markedly. Mutations in the genes encoding Nav1.5 and its accessory proteins have been associated with cardiac arrhythmias of significant...... and 23 were patients with Brugada syndrome. The effect of one variant was investigated functionally by patch-clamping CHO-K1 cells coexpressing Nav1.5 with MOG1. RESULTS: We uncovered a novel heterozygous nonsense variant, c.181G>T (p.E61X), that, however, was also present in control subjects, albeit...

Discovery and characterization of antibody variants using mass spectrometry-based comparative analysis for biosimilar candidates of monoclonal antibody drugs.

Science.gov (United States)

Li, Wenhua; Yang, Bin; Zhou, Dongmei; Xu, Jun; Ke, Zhi; Suen, Wen-Chen

2016-07-01

Liquid chromatography mass spectrometry (LC-MS) is the most commonly used technique for the characterization of antibody variants. MAb-X and mAb-Y are two approved IgG1 subtype monoclonal antibody drugs recombinantly produced in Chinese hamster ovary (CHO) cells. We report here that two unexpected and rare antibody variants have been discovered during cell culture process development of biosimilars for these two approved drugs through intact mass analysis. We then used comprehensive mass spectrometry-based comparative analysis including reduced light, heavy chains, and domain-specific mass as well as peptide mapping analysis to fully characterize the observed antibody variants. The "middle-up" mass comparative analysis demonstrated that the antibody variant from mAb-X biosimilar candidate was caused by mass variation of antibody crystalline fragment (Fc), whereas a different variant with mass variation in antibody antigen-binding fragment (Fab) from mAb-Y biosimilar candidate was identified. Endoproteinase Lys-C digested peptide mapping and tandem mass spectrometry analysis further revealed that a leucine to glutamine change in N-terminal 402 site of heavy chain was responsible for the generation of mAb-X antibody variant. Lys-C and trypsin coupled non-reduced and reduced peptide mapping comparative analysis showed that the formation of the light-heavy interchain trisulfide bond resulted in the mAb-Y antibody variant. These two cases confirmed that mass spectrometry-based comparative analysis plays a critical role for the characterization of monoclonal antibody variants, and biosimilar developers should start with a comprehensive structural assessment and comparative analysis to decrease the risk of the process development for biosimilars. Copyright © 2016 Elsevier B.V. All rights reserved.

Whey protein consumption after resistance exercise reduces energy intake at a post-exercise meal.

Science.gov (United States)

Monteyne, Alistair; Martin, Alex; Jackson, Liam; Corrigan, Nick; Stringer, Ellen; Newey, Jack; Rumbold, Penny L S; Stevenson, Emma J; James, Lewis J

2018-03-01

Protein consumption after resistance exercise potentiates muscle protein synthesis, but its effects on subsequent appetite in this context are unknown. This study examined appetite and energy intake following consumption of protein- and carbohydrate-containing drinks after resistance exercise. After familiarisation, 15 resistance training males (age 21 ± 1 years, body mass 78.0 ± 11.9 kg, stature 1.78 ± 0.07 m) completed two randomised, double-blind trials, consisting of lower-body resistance exercise, followed by consumption of a whey protein (PRO 23.9 ± 3.6 g protein) or dextrose (CHO 26.5 ± 3.8 g carbohydrate) drink in the 5 min post-exercise. An ad libitum meal was served 60 min later, with subjective appetite measured throughout. Drinks were flavoured and matched for energy content and volume. The PRO drink provided 0.3 g/kg body mass protein. Ad libitum energy intake (PRO 3742 ± 994 kJ; CHO 4172 ± 1132 kJ; P = 0.007) and mean eating rate (PRO 339 ± 102 kJ/min; CHO 405 ± 154 kJ/min; P = 0.009) were lower during PRO. The change in eating rate was associated with the change in energy intake (R = 0.661, P = 0.007). No interaction effects were observed for subjective measures of appetite. The PRO drink was perceived as creamier and thicker, and less pleasant, sweet and refreshing (P consumption after resistance exercise reduces subsequent energy intake, and this might be partially mediated by a reduced eating rate. Whilst this reduced energy intake is unlikely to impair hypertrophy, it may be of value in supporting an energy deficit for weight loss.

Interaction of insulin-like growth factor-I and insulin resistance-related genetic variants with lifestyle factors on postmenopausal breast cancer risk.

Science.gov (United States)

Jung, Su Yon; Ho, Gloria; Rohan, Thomas; Strickler, Howard; Bea, Jennifer; Papp, Jeanette; Sobel, Eric; Zhang, Zuo-Feng; Crandall, Carolyn

2017-07-01

Genetic variants and traits in metabolic signaling pathways may interact with obesity, physical activity, and exogenous estrogen (E), influencing postmenopausal breast cancer risk, but these inter-related pathways are incompletely understood. We used 75 single-nucleotide polymorphisms (SNPs) in genes related to insulin-like growth factor-I (IGF-I)/insulin resistance (IR) traits and signaling pathways, and data from 1003 postmenopausal women in Women's Health Initiative Observation ancillary studies. Stratifying via obesity and lifestyle modifiers, we assessed the role of IGF-I/IR traits (fasting IGF-I, IGF-binding protein 3, insulin, glucose, and homeostatic model assessment-insulin resistance) in breast cancer risk as a mediator or influencing factor. Seven SNPs in IGF-I and INS genes were associated with breast cancer risk. These associations differed between non-obese/active and obese/inactive women and between exogenous E non-users and users. The mediation effects of IGF-I/IR traits on the relationship between these SNPs and cancer differed between strata, but only roughly 35% of the cancer risk due to the SNPs was mediated by traits. Similarly, carriers of 20 SNPs in PIK3R1, AKT1/2, and MAPK1 genes (signaling pathways-genetic variants) had different associations with breast cancer between strata, and the proportion of the SNP-cancer relationship explained by traits varied 45-50% between the strata. Our findings suggest that IGF-I/IR genetic variants interact with obesity and lifestyle factors, altering cancer risk partially through pathways other than IGF-I/IR traits. Unraveling gene-phenotype-lifestyle interactions will provide data on potential genetic targets in clinical trials for cancer prevention and intervention strategies to reduce breast cancer risk.

Expression and fast preparation of biologically active recombinant human coagulation factor VII in CHO-K1 cells.

Science.gov (United States)

Xiao, W; Li, C Q; Xiao, X P; Lin, F Z

2013-12-16

Human coagulation factor VII (FVII) plays an important role in the blood coagulation process and exists in micro amounts in human plasma; therefore, any attempt at the large-scale production of FVII in significant quantities is challenging. The purpose of this study was to express and obtain biologically active recombinant FVII (rFVII) from Chinese hamster ovary K1 (CHO-K1) cells. The full-length FVII cDNA was isolated from a HepG2 cell line and then subcloned in pcDNA3.1 to construct an expression vector, pcDNA-FVII. CHO-K1 cells were transfected with 1 µg pcDNA-FVII. The cell line that stably expressed secretory FVII was screened using 900 µg/mL G418. The FVII copy number in CHO-K1 cells was detected by quantitative polymerase chain reaction (qPCR). The rFVII was purified in ligand affinity chromatography medium. The purified protein was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis. The biological activity of the purified FVII protein was determined by a prothrombin time assay. Three cell lines that permanently expressed rFVII were screened. The qPCR results demonstrated that each CHO-K1 cell harbored two FVII DNA copies. The SDS-PAGE and Western blot analysis showed that the purified protein was about 50 kDa. The purity of the target protein was 95%. The prothrombin time assay indicated that the FVII-specific activity of rFVII was 2573 ± 75 IU/mg. This method enabled the fast preparation of high-purity rFVII from CHO-K1 cells, and the purified protein had good biological activity.

Antigen Loss Variants: Catching Hold of Escaping Foes.

Science.gov (United States)

Vyas, Maulik; Müller, Rolf; Pogge von Strandmann, Elke

2017-01-01

Since mid-1990s, the field of cancer immunotherapy has seen steady growth and selected immunotherapies are now a routine and preferred therapeutic option of certain malignancies. Both active and passive cancer immunotherapies exploit the fact that tumor cells express specific antigens on the cell surface, thereby mounting an immune response specifically against malignant cells. It is well established that cancer cells typically lose surface antigens following natural or therapy-induced selective pressure and these antigen-loss variants are often the population that causes therapy-resistant relapse. CD19 and CD20 antigen loss in acute lymphocytic leukemia and chronic lymphocytic leukemia, respectively, and lineage switching in leukemia associated with mixed lineage leukemia (MLL) gene rearrangements are well-documented evidences in this regard. Although increasing number of novel immunotherapies are being developed, majority of these do not address the control of antigen loss variants. Here, we review the occurrence of antigen loss variants in leukemia and discuss the therapeutic strategies to tackle the same. We also present an approach of dual-targeting immunoligand effectively retargeting NK cells against antigen loss variants in MLL-associated leukemia. Novel immunotherapies simultaneously targeting more than one tumor antigen certainly hold promise to completely eradicate tumor and prevent therapy-resistant relapses.

Whey Protein Supplementation Enhances Whole Body Protein Metabolism and Performance Recovery after Resistance Exercise: A Double-Blind Crossover Study

Directory of Open Access Journals (Sweden)

Daniel W. D. West

2017-07-01

Full Text Available No study has concurrently measured changes in free-living whole body protein metabolism and exercise performance during recovery from an acute bout of resistance exercise. We aimed to determine if whey protein ingestion enhances whole body net protein balance and recovery of exercise performance during overnight (10 h and 24 h recovery after whole body resistance exercise in trained men. In a double-blind crossover design, 12 trained men (76 ± 8 kg, 24 ± 4 years old, 14% ± 5% body fat; means ± standard deviation (SD performed resistance exercise in the evening prior to consuming either 25 g of whey protein (PRO; MuscleTech 100% Whey or an energy-matched placebo (CHO immediately post-exercise (0 h, and again the following morning (~10 h of recovery. A third randomized trial, completed by the same participants, involving no exercise and no supplement served as a rested control trial (Rest. Participants ingested [15N]glycine to determine whole body protein kinetics and net protein balance over 10 and 24 h of recovery. Performance was assessed pre-exercise and at 0, 10, and 24 h of recovery using a battery of tests. Net protein balance tended to improve in PRO (P = 0.064; effect size (ES = 0.61, PRO vs. CHO during overnight recovery. Over 24 h, net balance was enhanced in PRO (P = 0.036 but not in CHO (P = 0.84; ES = 0.69, PRO vs. CHO, which was mediated primarily by a reduction in protein breakdown (PRO < CHO; P < 0.01. Exercise decreased repetitions to failure (REP, maximal strength (MVC, peak and mean power, and countermovement jump performance (CMJ at 0 h (all P < 0.05 vs. Pre. At 10 h, there were small-to-moderate effects for enhanced recovery of the MVC (ES = 0.56, mean power (ES = 0.49, and CMJ variables (ES: 0.27–0.49 in PRO. At 24 h, protein supplementation improved MVC (ES = 0.76, REP (ES = 0.44, and peak power (ES = 0.55. In conclusion, whey protein supplementation enhances whole body anabolism, and may improve acute recovery of

Molecular and cellular mechanisms of cadmium carcinogenesis

International Nuclear Information System (INIS)

Waisberg, Michael; Joseph, Pius; Hale, Beverley; Beyersmann, Detmar

2003-01-01

Cadmium is a heavy metal, which is widely used in industry, affecting human health through occupational and environmental exposure. In mammals, it exerts multiple toxic effects and has been classified as a human carcinogen by the International Agency for Research on Cancer. Cadmium affects cell proliferation, differentiation, apoptosis and other cellular activities. Cd 2+ does not catalyze Fenton-type reactions because it does not accept or donate electrons under physiological conditions, and it is only weakly genotoxic. Hence, indirect mechanisms are implicated in the carcinogenicity of cadmium. In this review multiple mechanisms are discussed, such as modulation of gene expression and signal transduction, interference with enzymes of the cellular antioxidant system and generation of reactive oxygen species (ROS), inhibition of DNA repair and DNA methylation, role in apoptosis and disruption of E-cadherin-mediated cell-cell adhesion. Cadmium affects both gene transcription and translation. The major mechanisms of gene induction by cadmium known so far are modulation of cellular signal transduction pathways by enhancement of protein phosphorylation and activation of transcription and translation factors. Cadmium interferes with antioxidant defense mechanisms and stimulates the production of reactive oxygen species, which may act as signaling molecules in the induction of gene expression and apoptosis. The inhibition of DNA repair processes by cadmium represents a mechanism by which cadmium enhances the genotoxicity of other agents and may contribute to the tumor initiation by this metal. The disruption of E-cadherin-mediated cell-cell adhesion by cadmium probably further stimulates the development of tumors. It becomes clear that there exist multiple mechanisms which contribute to the carcinogenicity of cadmium, although the relative weights of these contributions are difficult to estimate

Defect control in room temperature deposited cadmium sulfide thin films by pulsed laser deposition

Energy Technology Data Exchange (ETDEWEB)

Hernandez-Como, N. [Department of Materials Science and Engineering, University of Texas at Dallas, Richardson, TX, 75080 (United States); Martinez-Landeros, V. [Department of Materials Science and Engineering, University of Texas at Dallas, Richardson, TX, 75080 (United States); Centro de Investigación en Materiales Avanzados, Monterrey, Nuevo Leon, 66600, México (Mexico); Mejia, I. [Department of Materials Science and Engineering, University of Texas at Dallas, Richardson, TX, 75080 (United States); Aguirre-Tostado, F.S. [Centro de Investigación en Materiales Avanzados, Monterrey, Nuevo Leon, 66600, México (Mexico); Nascimento, C.D.; Azevedo, G. de M; Krug, C. [Instituto de Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, 91509-900 (Brazil); Quevedo-Lopez, M.A., E-mail: mquevedo@utdallas.edu [Department of Materials Science and Engineering, University of Texas at Dallas, Richardson, TX, 75080 (United States)

2014-01-01

The control of defects in cadmium sulfide thin films and its impact on the resulting CdS optical and electrical characteristics are studied. Sulfur vacancies and cadmium interstitial concentrations in the CdS films are controlled using the ambient pressure during pulsed laser deposition. CdS film resistivities ranging from 10{sup −1} to 10{sup 4} Ω-cm are achieved. Hall Effect measurements show that the carrier concentration ranges from 10{sup 19} to 10{sup 13} cm{sup −3} and is responsible for the observed resistivity variation. Hall mobility varies from 2 to 12 cm{sup 2}/V-s for the same pressure regime. Although the energy bandgap remains unaffected (∼ 2.42 eV), the optical transmittance is reduced due to the increase of defects in the CdS films. Rutherford back scattering spectroscopy shows the dependence of the CdS films stoichiometry with deposition pressure. The presence of CdS defects is attributed to more energetic species reaching the substrate, inducing surface damage in the CdS films during pulsed laser deposition. - Highlights: • CdS thin films deposited by pulsed laser deposition at room temperature. • The optical, electrical and structural properties were evaluated. • Carrier concentration ranged from 10{sup 19} to 10{sup 13} cm{sup −3}. • The chemical composition was studied by Rutherford back scattering. • The density of sulfur vacancies and cadmium interstitial was varied.

Cadmium in the bioenergy system - a synthesis

International Nuclear Information System (INIS)

Ahlfont, K.

1997-12-01

Cadmium is a toxic metal without any known positive biological effects. Both emissions and atmospheric deposition of cadmium have decreased radically in Sweden during recent years. In Sweden, about 150 tonnes of cadmium was supplied to the technosphere in 1990, mostly originating from NiCd batteries. More than 100 tonnes of cadmium accumulated in the technosphere. Mankind takes up cadmium from water, food and particulate atmospheric pollution. Even small amounts may be injurious in the long-term since the half-life in the kidneys is 30 years. Cadmium in biofuel and ashes are generally a cause of discussion. Ashes from biofuel constitute a nutrient resource that should be returned to the soil. A possible risk with spreading ashes is the spreading of heavy metals, and then foremost cadmium, which is among the heavy metals that forest soils are considered to tolerate the least. Several studies on cadmium in the bioenergy system have been made, both within the Research Programme for Recycling of Wood-ash, and within Vattenfall's Bioenergy Project. The present report is intended to provide a picture of the current state of knowledge and to review plans for the future With a 3 page summary in English. 51 refs, 1 fig, 3 tabs

Association of urinary cadmium and myocardial infarction

International Nuclear Information System (INIS)

Everett, Charles J.; Frithsen, Ivar L.

2008-01-01

We conducted a cross-sectional analysis of individuals 45-79 years old in the National Health and Nutrition Examination Survey III (1988-1994) (NHANES III). Myocardial infarction was determined by electrocardiogram (ECG). Our sample included 4912 participants, which when weighted represented 52,234,055 Americans. We performed adjusted logistic regressions with the Framingham risk score, pack-years of smoking, race-ethnicity, and family history of heart attack, and diabetes as covariates. Urinary cadmium ≥0.88 μg/g creatinine had an odds ratio of 1.86 (95% CI 1.26-2.75) compared to urinary cadmium <0.43 μg/g creatinine. This result supports the hypothesis that cadmium is associated with coronary heart disease. When logistic regressions were done by gender, women, but not men, showed a significant association of urinary cadmium with myocardial infarction. Women with urinary cadmium ≥0.88 μg/g creatinine had an odds ratio of 1.80 (95% CI 1.06-3.04) compared to urinary cadmium <0.43 μg/g creatinine. When the analysis was restricted to never smokers (N=2187) urinary cadmium ≥0.88 μg/g creatinine had an odds ratio of 1.85 (95% CI 1.10-3.14) compared to urinary cadmium <0.43 μg/g creatinine

Cadmium action in synapses in the brain

International Nuclear Information System (INIS)

Minami, Akira; Takeda, Atsushi; Nishibaba, Daisuke; Tekefuta, Sachiyo; Oku, Naoto

2001-01-01

Chronic exposure to cadmium causes central nervous system disorders, e.g., olfactory dysfunction. To clarify cadmium toxicity in synaptic neurotransmission in the brain, the movement and action of cadmium in the synapses was examined using in vivo microdialysis. One and 24 h after injection of 109 CdCl 2 into the amygdala of rats, 109 Cd release into the extracellular space was facilitated by stimulation with high K + , suggesting that cadmium taken up in amygdalar neurons is released into the synaptic clefts in a calcium- and impulse-dependent manner. To examine the action of cadmium in the synapses, the amygdala was perfused with artificial cerebrospinal fluid containing 10-30 μM CdCl 2 . The release of excitatory neurotransmitters, i.e., glutamate and aspartate, into the extracellular space was decreased during perfusion with cadmium, while the release of inhibitory neurotransmitters, i.e., glycine and γ-amino butyric acid (GABA), into the extracellular space was increased during the period. These results suggest that cadmium released from the amygdalar neuron terminals affects the degree and balance of excitation-inhibition in synaptic neurotransmission. (author)

Standard specification for nuclear-grade silver-indium-cadmium alloy

CERN Document Server

American Society for Testing and Materials. Philadelphia

2003-01-01

1.1 This specification covers silver-indium-cadmium alloy for use as a control material in light-water nuclear reactors. 1.2 The scope of this specification excludes the use of this material in applications where material strength of this alloy is a prime requisite. Also, this material must be protected from the primary water by a corrosion and wear resistant cladding. 1.3 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.

Prevalence of Smqnr and plasmid-mediated quinolone resistance determinants in clinical isolates of Stenotrophomonas maltophilia from Japan: novel variants of Smqnr

Directory of Open Access Journals (Sweden)

H. Kanamori

2015-09-01

Full Text Available Stenotrophomonas maltophilia is an important pathogen in healthcare-associated infections. S. maltophilia may contain Smqnr, a quinolone resistance gene encoding the pentapeptide repeat protein, which confers low-level quinolone resistance upon expression in a heterologous host. We investigated the prevalence of Smqnr and plasmid-mediated quinolone resistance (PMQR determinants in S. maltophilia isolates from Japan. A total of 181 consecutive and nonduplicate clinical isolates of S. maltophilia were collected from four areas of Japan. The antimicrobial susceptibility profiles for these strains were determined. PCR was conducted for Smqnr and PMQR genes, including qnrA, qnrB, qnrC, qnrS, aac(6′-Ib and qepA. PCR products for Smqnr and aac(6′-Ib were sequenced. For the S. maltophilia isolates containing Smqnr, pulsed-field gel electrophoresis (PFGE was performed using XbaI. Resistance rates to ceftazidime, levofloxacin, trimethoprim–sulfamethoxazole, chloramphenicol and minocycline were 67.4%, 6.1%, 17.7%, 8.8% and 0%, respectively. The minimum inhibitory concentration required to inhibit the growth of 50% and 90% of organisms were 0.5 and 2 mg/L for moxifloxacin but 1 and 4 mg/L for levofloxacin, respectively. Smqnr was detected in 104 of the 181 S. maltophilia isolates (57.5%, and the most frequent was Smqnr6, followed by Smqnr8 and Smqnr11. Eleven novel variants from Smqnr48 to Smqnr58 were detected. The 24 Smqnr-containing S. maltophilia isolates were typed by PFGE and divided into 21 unique types. Nine S. maltophilia isolates (5.0% carried aac(6′-Ib-cr. No qnr or qepA genes were detected. This study describes a high prevalence of Smqnr and novel variants of Smqnr among S. maltophilia from Japan. Continuous antimicrobial surveillance and further molecular epidemiological studies on quinolone resistance in S. maltophilia are needed.

Distribution of cadmium between calcium carbonate and solution, 2

International Nuclear Information System (INIS)

Kitano, Yasushi; Kanamori, Nobuko; Fujiyoshi, Ryoko

1978-01-01

The distribution coefficient of cadmium between calcite and solution has been measured in the calcium bicarbonate solution containing cadmium and chloride ions, which forms complexes with cadmium ions. It has been confirmed experimentally that cadmium carbonate is present as a solid solution between calcitic calcium carbonate and cadmium carbonate in the carbonate precipitate formed in the solution system. However, the constant value of the thermodynamic distribution coefficient of cadmium between calcite and solution has not been obtained experimentally in the calcium bicarbonate solution containing cadmium and chloride ions. It may have been caused by the very specific behavior of cadmium ions, but the exact reason remains unsolved and must be studied. (Kobatake, H.)

Correlations of urinary cadmium with hypertension and diabetes in persons living in cadmium-contaminated villages in northwestern Thailand: A population study

Energy Technology Data Exchange (ETDEWEB)

Swaddiwudhipong, Witaya, E-mail: swaddi@hotmail.com [Department of Community and Social Medicine, Mae Sot General Hospital, Tak 63110 (Thailand); Mahasakpan, Pranee [Department of Community and Social Medicine, Mae Sot General Hospital, Tak 63110 (Thailand); Limpatanachote, Pisit; Krintratun, Somyot [Department of Internal Medicine, Mae Sot General Hospital, Tak (Thailand)

2010-08-15

Risk for hypertension and diabetes has not been conclusively found to be a result of cadmium exposure. A population-based study was conducted in 2009 to examine the correlations of urinary cadmium, a good biomarker of long-term cadmium exposure, with hypertension and diabetes in persons aged 35 years and older who lived in the 12 cadmium-contaminated rural villages in northwestern Thailand. A total of 5273 persons were interviewed and screened for urinary cadmium, hypertension, and diabetes. The geometric mean level of urinary cadmium for women (2.4{+-}2.3 {mu}g/g creatinine) was significantly greater than that for men (2.0{+-}2.2 {mu}g/g creatinine). Hypertension was presented in 29.8% of the study population and diabetes was detected in 6.6%. The prevalence of hypertension significantly increased from 25.0% among persons in the lowest tertile of urinary cadmium to 35.0% in the highest tertile. In women, the rate of hypertension significantly increased with increasing urinary cadmium levels in both ever and never smokers, after adjusting for age, alcohol consumption, body mass index, and diabetes. In men, such association was less significantly found in never smokers. The study revealed no significant association between urinary cadmium and diabetes in either gender. Our study supports the hypothesis that environmental exposure to cadmium may increase the risk of hypertension. Risk for diabetes in relation to cadmium exposure remains uncertain in this exposed population.

Correlations of urinary cadmium with hypertension and diabetes in persons living in cadmium-contaminated villages in northwestern Thailand: A population study

International Nuclear Information System (INIS)

Swaddiwudhipong, Witaya; Mahasakpan, Pranee; Limpatanachote, Pisit; Krintratun, Somyot

2010-01-01

Risk for hypertension and diabetes has not been conclusively found to be a result of cadmium exposure. A population-based study was conducted in 2009 to examine the correlations of urinary cadmium, a good biomarker of long-term cadmium exposure, with hypertension and diabetes in persons aged 35 years and older who lived in the 12 cadmium-contaminated rural villages in northwestern Thailand. A total of 5273 persons were interviewed and screened for urinary cadmium, hypertension, and diabetes. The geometric mean level of urinary cadmium for women (2.4±2.3 μg/g creatinine) was significantly greater than that for men (2.0±2.2 μg/g creatinine). Hypertension was presented in 29.8% of the study population and diabetes was detected in 6.6%. The prevalence of hypertension significantly increased from 25.0% among persons in the lowest tertile of urinary cadmium to 35.0% in the highest tertile. In women, the rate of hypertension significantly increased with increasing urinary cadmium levels in both ever and never smokers, after adjusting for age, alcohol consumption, body mass index, and diabetes. In men, such association was less significantly found in never smokers. The study revealed no significant association between urinary cadmium and diabetes in either gender. Our study supports the hypothesis that environmental exposure to cadmium may increase the risk of hypertension. Risk for diabetes in relation to cadmium exposure remains uncertain in this exposed population.

Tubulin posttranslational modifications induced by cadmium in the sponge Clathrina clathrus

Energy Technology Data Exchange (ETDEWEB)

Ledda, F.D., E-mail: f.ledda@hotmail.it [Dipartimento di Scienze della Terra, dell’Ambiente e della Vita (DISTAV), Università di Genova, Corso Europa 26, I-16132 Genova (Italy); Dipartimento di Scienze della Natura e del Territorio (DIPNET), Università di Sassari, Via Muroni 25, I-07100 Sassari (Italy); Ramoino, P. [Dipartimento di Scienze della Terra, dell’Ambiente e della Vita (DISTAV), Università di Genova, Corso Europa 26, I-16132 Genova (Italy); Ravera, S. [Dipartimento di Farmacia (DIFAR), Viale Cembrano 4, I-16147 Genova (Italy); Perino, E. [Dipartimento di Scienze della Terra, dell’Ambiente e della Vita (DISTAV), Università di Genova, Corso Europa 26, I-16132 Genova (Italy); Bianchini, P. [Istituto Italiano di Tecnologia (IIT), Dipartimento di Nanofisica, Via Morego 30, I-16163 Genova (Italy); Diaspro, A. [Istituto Italiano di Tecnologia (IIT), Dipartimento di Nanofisica, Via Morego 30, I-16163 Genova (Italy); Dipartimento di Fisica (DIFI), Università di Genova, Via Dodecaneso 33, I-16146 Genova (Italy); Gallus, L.; Pronzato, R. [Dipartimento di Scienze della Terra, dell’Ambiente e della Vita (DISTAV), Università di Genova, Corso Europa 26, I-16132 Genova (Italy); Manconi, R. [Dipartimento di Scienze della Natura e del Territorio (DIPNET), Università di Sassari, Via Muroni 25, I-07100 Sassari (Italy)

2013-09-15

Highlights: •The effect of Cd{sup 2+} on Clathrina clathrus microtubule network was studied. •Cd{sup 2+} exposure increases acetylated and detyrosinated α-tubulin levels. •Microtubules enriched in acetylated/detyrosinated α-tubulin were resistant to cold. •Clathrina clathrus exposed to Cd{sup 2+} showed cytoplasmic microtubules with an enhanced stability. -- Abstract: As sessile filter feeders, sponges are exposed to environmental stress due to pollutants of both anthropogenic and natural origins and are able to accumulate harmful substances. Thus, sponges are considered a good tool for the biomonitoring of coastal areas. In this study, we used biochemical and immunocytochemical analyses to provide new data on the cadmium-related changes in sponge cells. In particular, we analyzed the effects of different concentrations of cadmium on the microtubule network in the calcisponge Clathrina clathrus. Quantitative densitometry of the immunoblots showed that, while the levels of α- and β-tubulin remained relatively constant in C. clathrus when exposed to 1 and 5 μM CdCl{sub 2}, there were progressive shifts in the levels of some tubulin isoforms. Exposure for 24 h to sublethal concentrations of cadmium reduced the level of tyrosinated α-tubulin and enhanced the levels of acetylated and detyrosinated α-tubulin relative to the levels in controls. Confocal microscopy analysis of immunolabeled tissue sections showed that the inhibitory effect of cadmium was associated with a decrease in the labeling of the cells with a monoclonal antibody that recognizes tyrosinated α-tubulin. By contrast, the reactivity with a monoclonal antibody that recognizes acetylated α-tubulin and with a polyclonal antibody specific for detyrosinated α-tubulin was enhanced at the same time points. Because the acetylation and detyrosination of α-tubulin occur on stable microtubules, the marked enhancement of α-tubulin acetylation and detyrosination in Cd{sup 2+}-treated cells

Modelling of cadmium fluxes on energy crop land

International Nuclear Information System (INIS)

Palm, V.

1992-04-01

The flux of cadmium on energy crop land is investigated. Three mechanisms are accounted for; Uptake by plant, transport with water, and sorption to soil. Sorption is described with Freundlich isotherms. The system is simulated mathematically in order to estimate the sensitivity and importance of different parameters on the cadmium flow and sorption. The water flux through the soil and the uptake by plants are simulated with a hydrological model, SOIL. The simulated time period is two years. The parameters describing root distribution and evaporation due to crop are taken from measurements on energy crop (Salix). The resulting water flux, water content in the soil profile and the water uptake into roots, for each day and soil compartment, are used in the cadmium sorption simulation. In the cadmium sorption simulation the flux and equilibrium chemistry of cadmium is calculated. It is shown that the amount of cadmium that accumulates in the plant, and the depth to which the applied cadmium reaches depends strongly on the constants in the sorption isotherm. With an application of 10 mg Cd/m 2 in the given range of Freundlich equations, the simulations gave a plant uptake of between 0 and 30 % of the applied cadmium in two years. At higher concentrations, where cadmium sorption can be described by nonlinear isotherms, more cadmium is present in soil water and is generally more bioavailable. 25 refs

Zinc-induced protection against cadmium

Energy Technology Data Exchange (ETDEWEB)

Early, J.L.; Schnell, R.C.

1978-02-01

Pretreatment of male rats with cadmium acetate potentiates the duration of hexobarbital hypnosis and inhibits the rate of hepatic microsomal drug metabolism. Pretreatment of rats with zinc acetate protects against these alterations in drug action elicited by cadmium.

Real-time quantitative PCR for retrovirus-like particle quantification in CHO cell culture.

Science.gov (United States)

de Wit, C; Fautz, C; Xu, Y

2000-09-01

Chinese hamster ovary (CHO) cells have been widely used to manufacture recombinant proteins intended for human therapeutic uses. Retrovirus-like particles, which are apparently defective and non-infectious, have been detected in all CHO cells by electron microscopy (EM). To assure viral safety of CHO cell-derived biologicals, quantification of retrovirus-like particles in production cell culture and demonstration of sufficient elimination of such retrovirus-like particles by the down-stream purification process are required for product market registration worldwide. EM, with a detection limit of 1x10(6) particles/ml, is the standard retrovirus-like particle quantification method. The whole process, which requires a large amount of sample (3-6 litres), is labour intensive, time consuming, expensive, and subject to significant assay variability. In this paper, a novel real-time quantitative PCR assay (TaqMan assay) has been developed for the quantification of retrovirus-like particles. Each retrovirus particle contains two copies of the viral genomic particle RNA (pRNA) molecule. Therefore, quantification of retrovirus particles can be achieved by quantifying the pRNA copy number, i.e. every two copies of retroviral pRNA is equivalent to one retrovirus-like particle. The TaqMan assay takes advantage of the 5'-->3' exonuclease activity of Taq DNA polymerase and utilizes the PRISM 7700 Sequence Detection System of PE Applied Biosystems (Foster City, CA, U.S.A.) for automated pRNA quantification through a dual-labelled fluorogenic probe. The TaqMan quantification technique is highly comparable to the EM analysis. In addition, it offers significant advantages over the EM analysis, such as a higher sensitivity of less than 600 particles/ml, greater accuracy and reliability, higher sample throughput, more flexibility and lower cost. Therefore, the TaqMan assay should be used as a substitute for EM analysis for retrovirus-like particle quantification in CHO cell

Analysis and metabolic engineering of lipid-linked oligosaccharides in glycosylation-deficient CHO cells

International Nuclear Information System (INIS)

Jones, Meredith B.; Tomiya, Noboru; Betenbaugh, Michael J.; Krag, Sharon S.

2010-01-01

Glycosylation-deficient Chinese Hamster Ovary (CHO) cell lines can be used to expand our understanding of N-glycosylation pathways and to study Congenital Disorders of Glycosylation, diseases caused by defects in the synthesis of N-glycans. The mammalian N-glycosylation pathway involves the step-wise assembly of sugars onto a dolichol phosphate (P-Dol) carrier, forming a lipid-linked oligosaccharide (LLO), followed by the transfer of the completed oligosaccharide onto the protein of interest. In order to better understand how deficiencies in this pathway affect the availability of the completed LLO donor for use in N-glycosylation, we used a non-radioactive, HPLC-based assay to examine the intermediates in the LLO synthesis pathway for CHO-K1 cells and for three different glycosylation-deficient CHO cell lines. B4-2-1 cells, which have a mutation in the dolichol phosphate-mannose synthase (DPM2) gene, accumulated LLO with the structure Man 5 GlcNAc 2 -P-P-Dol, while MI8-5 cells, which lack glucosyltransferase I (ALG6) activity, accumulated Man 9 GlcNAc 2 -P-P-Dol. CHO-K1 and MI5-4 cells both produced primarily the complete LLO, Glc 3 Man 9 GlcNAc 2 -P-P-Dol, though the relative quantity was lower in MI5-4. MI5-4 cells have reduced hexokinase activity which could affect the availability of many of the substrates required for LLO synthesis and, consequently, impair production of the final LLO donor. Increasing hexokinase activity by overexpressing hexokinase II in MI5-4 caused a decrease in the relative quantities of the incomplete LLO intermediates from Man 5 GlcNAc 2 -PP-Dol through Glc 1 Man 9 GlcNAc 2 -PP-Dol, and an increase in the relative quantity of the final LLO donor, Glc 3 Man 9 GlcNAc 2 -P-P-Dol. This study suggests that metabolic engineering may be a useful strategy for improving LLO availability for use in N-glycosylation.

Analysis and metabolic engineering of lipid-linked oligosaccharides in glycosylation-deficient CHO cells

Energy Technology Data Exchange (ETDEWEB)

Jones, Meredith B., E-mail: mbauman7@jhu.edu [Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 North Charles Street, Maryland Hall 221, Baltimore, MD 21218 (United States); Tomiya, Noboru, E-mail: ntomiya1@jhu.edu [Department of Biology, Johns Hopkins University, 3400 North Charles Street, Mudd Hall 104A, Baltimore, MD 21218 (United States); Betenbaugh, Michael J., E-mail: beten@jhu.edu [Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 North Charles Street, Maryland Hall 221, Baltimore, MD 21218 (United States); Krag, Sharon S., E-mail: skrag@jhsph.edu [Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205 (United States)

2010-04-23

Glycosylation-deficient Chinese Hamster Ovary (CHO) cell lines can be used to expand our understanding of N-glycosylation pathways and to study Congenital Disorders of Glycosylation, diseases caused by defects in the synthesis of N-glycans. The mammalian N-glycosylation pathway involves the step-wise assembly of sugars onto a dolichol phosphate (P-Dol) carrier, forming a lipid-linked oligosaccharide (LLO), followed by the transfer of the completed oligosaccharide onto the protein of interest. In order to better understand how deficiencies in this pathway affect the availability of the completed LLO donor for use in N-glycosylation, we used a non-radioactive, HPLC-based assay to examine the intermediates in the LLO synthesis pathway for CHO-K1 cells and for three different glycosylation-deficient CHO cell lines. B4-2-1 cells, which have a mutation in the dolichol phosphate-mannose synthase (DPM2) gene, accumulated LLO with the structure Man{sub 5}GlcNAc{sub 2}-P-P-Dol, while MI8-5 cells, which lack glucosyltransferase I (ALG6) activity, accumulated Man{sub 9}GlcNAc{sub 2}-P-P-Dol. CHO-K1 and MI5-4 cells both produced primarily the complete LLO, Glc{sub 3}Man{sub 9}GlcNAc{sub 2}-P-P-Dol, though the relative quantity was lower in MI5-4. MI5-4 cells have reduced hexokinase activity which could affect the availability of many of the substrates required for LLO synthesis and, consequently, impair production of the final LLO donor. Increasing hexokinase activity by overexpressing hexokinase II in MI5-4 caused a decrease in the relative quantities of the incomplete LLO intermediates from Man{sub 5}GlcNAc{sub 2}-PP-Dol through Glc{sub 1}Man{sub 9}GlcNAc{sub 2}-PP-Dol, and an increase in the relative quantity of the final LLO donor, Glc{sub 3}Man{sub 9}GlcNAc{sub 2}-P-P-Dol. This study suggests that metabolic engineering may be a useful strategy for improving LLO availability for use in N-glycosylation.

Large silver-cadmium technology program

Science.gov (United States)

Charlip, S.; Lerner, S.

1971-01-01

The effects of varying cell design on operation factors on the electrochemical performance of sealed, silver-cadmium cells were determined. A factorial experiment was conducted for all test cells constructed with organic separators. Three operating factors were evaluated: temperature, depth of discharge, and charge rate. The six construction factors considered were separator, absorber, electrolyte quantity, cadmium electrode type, cadmium-to-silver ratio, and auxiliary electrode. Test cells of 4 ampere-hour capacity were fabricated and cycled. The best performing cells, on a 94 minute orbit, at 40% depth of discharge, were those containing silver-treated fibrous sausage casings as the separator, and Teflon-ated, pressed cadmium electrodes. Cycling data of cells with inorganic separators (Astroset) are given. Best performance was shown by cells with nonwoven nylon absorbers. Rigid inorganic separators provided the best barrier to silver migration.

Effect of 7 days of exercise on exogenous carbohydrate oxidation and insulin resistance in children with obesity.

Science.gov (United States)

Chu, Lisa; Morrison, Katherine M; Riddell, Michael C; Raha, Sandeep; Timmons, Brian W

2018-07-01

The capacity to match carbohydrate (CHO) oxidation with CHO availability (deemed metabolic flexibility (MetFlex)) may be important for type 2 diabetes prevention. In adults, impaired MetFlex is associated with insulin resistance (IR), which can be improved with as little as 7 days of exercise. Whether this occurs similarly in children is unknown. We hypothesized that 7 consecutive days of exercise would improve MetFlex and IR in children with obesity. Twelve children (8 boys, 4 girls) completed 2 study visits before (PRE) and 2 study visits after (POST) exercise training. At visit 1, fasting blood was collected, and anthropometry and maximal oxygen uptake were assessed. At visit 2, a 13 C-enriched CHO drink was ingested before exercise (3 × 20 min) at ∼59% maximal oxygen uptake. Exogenous CHO oxidative efficiency, used as a surrogate measurement of MetFlex, was calculated from breath samples. During training, participants alternated between continuous and high-intensity interval cycling sessions at home under supervision. In spite of good training adherence, there was no improvement in MetFlex (PRE: 20.7% ± 1.8%, POST: 18.9% ± 4.9%, p = 0.22) or homeostasis model assessment of insulin resistance (PRE: 8.7 ± 4.6, POST: 8.1 ± 6.0, p = 0.51). Future research should investigate exercise volume, sex, and pubertal effects on the early responsiveness of MetFlex to exercise therapy.

Isolation and characterization of variant clones of Chinese hamster cells after treatment with irradiated 5-iodouridine

International Nuclear Information System (INIS)

Kuroda, Y.; Yokoiyama, A.; Kada, T.

1975-01-01

Variant clones were isolated from cultured Chinese hamster Don cells after treatment with irradiated 5-iodouridine. The following characters of a primary variant clone, C-11 and a secondary variant clone, C-24 were compared with those of the original clone C-1: colony-forming activity, growth rate in the presence of irradiated and unirradiated 5-iodouridine, distribution of chromosome numbers and cell cohesion. The variant clones C-11 and C-24 were partially resistant to unirradiated 5-iodouridine at lower concentration and C-24 cells were slightly resistant to short-term treatment with irradiated 5-iodouridine. Unlike clones C-1 and C-11, the variant clone C-24 showed no lag phase on growth in 5-iodouridine medium. The modal numbers of the chromosomes of all three clones were 22, like that of normal Chinese hamster diploid cells. Of the three clones, the variant C-24 cells showed the least mutual cohesion and the original C-1 cells showed the most. The possibility that an alteration in cellular membrane might be related to an increase in the resistance to radiosensitizing agents was discussed

Immunochromatographic assay of cadmium levels in oysters.

Science.gov (United States)

Nishi, Kosuke; Kim, In-Hae; Itai, Takaaki; Sugahara, Takuya; Takeyama, Haruko; Ohkawa, Hideo

2012-08-15

Oysters are one of foodstuffs containing a relatively high amount of cadmium. Here we report on establishment of an immunochromatographic assay (ICA) method of cadmium levels in oysters. Cadmium was extracted with 0.l mol L(-1) HCl from oysters and cleaned up from other metals by the use of an anion-exchange column. The behavior of five metals Mn, Fe, Cu, Zn, and Cd was monitored at each step of extraction and clean-up procedure for the ICA method in an inductively coupled plasma-mass spectrometry (ICP-MS) analysis. The results revealed that a simple extraction method with the HCl solution was efficient enough to extract almost all of cadmium from oysters. Clean-up with an anion-exchange column presented almost no loss of cadmium adsorbed on the column and an efficient removal of metals other than cadmium. When a spiked recovery test was performed in the ICA method, the recovery ranged from 98% to 112% with relative standard deviations between 5.9% and 9.2%. The measured values of cadmium in various oyster samples in the ICA method were favorably correlated with those in ICP-MS analysis (r(2)=0.97). Overall results indicate that the ICA method established in the present study is an adequate and reliable detection method for cadmium levels in oysters. Copyright © 2012 Elsevier B.V. All rights reserved.

Mechanism of Nisin, Pediocin 34, and Enterocin FH99 Resistance in Listeria monocytogenes.

Science.gov (United States)

Kaur, Gurpreet; Singh, Tejinder Pal; Malik, Ravinder Kumar; Bhardwaj, Arun

2012-03-01

Nisin-, pediocin 34-, and enterocin FH99-resistant variants of Listeria monocytogenes ATCC 53135 were developed. In an attempt to clarify the possible mechanisms underlying bacteriocin resistance in L. monocytogenes ATCC 53135, sensitivity of the resistant strains of L. monocytogenes ATCC 53135 to nisin, pediocin 34, and enterocin FH99 in the absence and presence of different divalent cations was assessed, and the results showed that the addition of divalent cations significantly reduced the inhibitory activity of nisin, pediocin 34, and enterocin FH99 against resistant variants of L. monocytogenes ATCC 53135. The addition of EDTA, however, restored this activity suggesting that the divalent cations seem to affect the initial electrostatic interaction between the positively charged bacteriocin and the negatively charged phospholipids of the membrane. Nisin-, pediocin 34-, and enterocin-resistant variants of L. monocytogenes ATCC 53135 were more resistant to lysozyme as compared to the wild-type strain both in the presence as well as absence of nisin, pediocin 34, and enterocin FH99. Ultra structural profiles of bacteriocin-sensitive L. monocytogenes and its bacteriocin-resistant counterparts revealed that the cells of wild-type strain of L. monocytogenes were maximally in pairs or short chains, whereas, its nisin-, pediocin 34-, and enterocin FH99-resistant variants tend to form aggregates. Results indicated that without a cell wall, the acquired nisin, pediocin 34, and enterocin FH99 resistance of the variants was lost. Although the bacteriocin-resistant variants appeared to lose their acquired resistance toward nisin, pediocin 34, and enterocin FH99, the protoplasts of the resistant variants appeared to be more resistant to bacteriocins than the protoplasts of their wild-type counterparts.

Engineer medium and feed for modulating N-glycosylation of recombinant protein production in CHO cell culture

DEFF Research Database (Denmark)

Fan, Yuzhou; Kildegaard, Helene Faustrup; Andersen, Mikael Rørdam

2017-01-01

Chinese hamster ovary (CHO) cells have become the primary expression system for the production of complex recombinant proteins due to their long-term success in industrial scale production and generating appropriate protein N-glycans similar to that of humans. Control and optimization of protein N......-glycosylation is crucial, as the structure of N-glycans can largely influence both biological and physicochemical properties of recombinant proteins. Protein N-glycosylation in CHO cell culture can be controlled and tuned by engineering medium, feed, culture process, as well as genetic elements of the cell...

Cadmium action in synapses in the brain

Energy Technology Data Exchange (ETDEWEB)

Minami, Akira; Takeda, Atsushi; Nishibaba, Daisuke; Tekefuta, Sachiyo; Oku, Naoto [Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka (Japan)

2001-05-01

Chronic exposure to cadmium causes central nervous system disorders, e.g., olfactory dysfunction. To clarify cadmium toxicity in synaptic neurotransmission in the brain, the movement and action of cadmium in the synapses was examined using in vivo microdialysis. One and 24 h after injection of {sup 109}CdCl{sub 2} into the amygdala of rats, {sup 109}Cd release into the extracellular space was facilitated by stimulation with high K{sup +}, suggesting that cadmium taken up in amygdalar neurons is released into the synaptic clefts in a calcium- and impulse-dependent manner. To examine the action of cadmium in the synapses, the amygdala was perfused with artificial cerebrospinal fluid containing 10-30 {mu}M CdCl{sub 2}. The release of excitatory neurotransmitters, i.e., glutamate and aspartate, into the extracellular space was decreased during perfusion with cadmium, while the release of inhibitory neurotransmitters, i.e., glycine and {gamma}-amino butyric acid (GABA), into the extracellular space was increased during the period. These results suggest that cadmium released from the amygdalar neuron terminals affects the degree and balance of excitation-inhibition in synaptic neurotransmission. (author)

Role of Androgen Receptor Variants in Prostate Cancer: Report from the 2017 Mission Androgen Receptor Variants Meeting.

Science.gov (United States)

Luo, Jun; Attard, Gerhardt; Balk, Steven P; Bevan, Charlotte; Burnstein, Kerry; Cato, Laura; Cherkasov, Artem; De Bono, Johann S; Dong, Yan; Gao, Allen C; Gleave, Martin; Heemers, Hannelore; Kanayama, Mayuko; Kittler, Ralf; Lang, Joshua M; Lee, Richard J; Logothetis, Christopher J; Matusik, Robert; Plymate, Stephen; Sawyers, Charles L; Selth, Luke A; Soule, Howard; Tilley, Wayne; Weigel, Nancy L; Zoubeidi, Amina; Dehm, Scott M; Raj, Ganesh V

2018-05-01

Although a number of studies have demonstrated the importance of constitutively active androgen receptor variants (AR-Vs) in prostate cancer, questions still remain about the precise role of AR-Vs in the progression of castration-resistant prostate cancer (CRPC). Key stakeholders and opinion leaders in prostate cancer convened on May 11, 2017 in Boston to establish the current state of the field of AR-Vs. The meeting "Mission Androgen Receptor Variants" was the second of its kind sponsored by the Prostate Cancer Foundation (PCF). This invitation-only event was attended by international leaders in the field and representatives from sponsoring organizations (PCF and industry sponsors). Eighteen faculty members gave short presentations, which were followed by in-depth discussions. Discussions focused on three thematic topics: (1) potential of AR-Vs as biomarkers of therapeutic resistance; (2) role of AR-Vs as functionally active CRPC progression drivers; and (3) utility of AR-Vs as therapeutic targets in CRPC. The three meeting organizers synthesized this meeting report, which is intended to summarize major data discussed at the meeting and identify key questions as well as strategies for addressing these questions. There was a critical consensus that further study of the AR-Vs is an important research focus in CRPC. Contrasting views and emphasis, each supported by data, were presented at the meeting, discussed among the participants, and synthesized in this report. This article highlights the state of knowledge and outlines the most pressing questions that need to be addressed to advance the AR-V field. Although further investigation is needed to delineate the role of androgen receptor (AR) variants in metastatic castration-resistant prostate cancer, advances in measurement science have enabled development of blood-based tests for treatment selection. Detection of AR variants (eg, AR-V7) identified a patient population with poor outcomes to existing AR

Critical review of animal carcinogenesis by cadmium and its inorganic compounds

International Nuclear Information System (INIS)

Maximilien, R.; Dero, B.

1990-01-01

Animal carcinogenic biassays relative to 6 inorganic cadmium substances (cadmium metal, cadmium oxide, cadmium sulfide, cadmium sulfate, cadmium chloride and cadmium acetate) are reviewed (speciation). Critical evaluation of literature data on carcinogenicity has been performed by making reference to E.C. guidelines of good laboratory practice. There are few data on routes relevant for human risk assessment: experiments on inhalation demonstrate lung carcinogenicity of cadmium oxide, cadmium sulfide, cadmium sulfate and cadmium chloride in rats but not in mice nor in hamsters; no carcinogenic effects of cadmium compounds are observed following oral administration. For routes of less or no relevance for human risk assessment, some results are clearly positive: subcutaneous injection induces cancers in situ (various cadmium compounds), testicular tumours (cadmium sulfate and cadmium chloride) and prostatic tumours (cadmium chloride) but such effects are not observed using relevant malignancies in rats. With respect to other no relevant routes (intraperitoneal, intrarenal...) tumours are incidentally produced in situ, but not in remote organs. Numerous studies fail to demonstrate cadmium carcinogenicity, but methodologically acceptable negative ones are very limited in number. Accordingly strain dependent effects and dose effect relationship could not be thoroughly assessed

Growth of cadmium oxide whiskers on cadmium sulphide single crystals with copper as growth activator

Energy Technology Data Exchange (ETDEWEB)

Koparanova, N.; Simov, S. (Bylgarska Akademiya na Naukite, Sofia. Inst. po Fizika na Tvyrdoto Tyalo); Genchev, D. (Bylgarska Akademiya na Naukite, Sofia. Inst. za Yadrena Izsledvaniya i Yadrena Energetika); Metchenov, G. (Research Inst. of Criminalistics and Criminology, Sofia (Bulgaria))

1985-02-01

Some results on the growth and morphology of cadmium oxide whiskers, obtained on cadmium sulphide single crystals with copper as a growth activator, are presented in this work. Cadmium oxide whiskers have been obtained on brace 112-bar0 brace faces of cadmium sulphide plates with a copper layer deposited in advance. The whiskers grew during the annealing of the plates in a weak stream of technically pure argon at temperatures 670 to 730 deg C for 15 min to 3.5 h. Details about the procedure have been given elsewhere. The composition and morphology of the whiskers have been studied by an X-ray microanalyser JEOL 35 DDS and a scanning electron microscope JEOL, JSM 35. The optical microscopic observations have shown that after annealing, a gray-black granular layer is formed on the cadmium sulphide single crystals and this layer can easily be separated from the crystal substrate. Under the granular layer the crystal is heavily damaged. The whiskers grow on the granular layer and they are coloured yellow-brown or red-brown. The maximum whisker length attains several hundreds of micrometres and in some cases up to 1 mm or more.

Growth of cadmium oxide whiskers on cadmium sulphide single crystals with copper as growth activator

International Nuclear Information System (INIS)

Koparanova, N.; Simov, S.

1985-01-01

Some results on the growth and morphology of cadmium oxide whiskers, obtained on cadmium sulphide single crystals with copper as a growth activator, are presented in this work. Cadmium oxide whiskers have been obtained on brace 112-bar0 brace faces of cadmium sulphide plates with a copper layer deposited in advance. The whiskers grew during the annealing of the plates in a weak stream of technically pure argon at temperatures 670 to 730 deg C for 15 min to 3.5 h. Details about the procedure have been given elsewhere. The composition and morphology of the whiskers have been studied by an X-ray microanalyser JEOL 35 DDS and a scanning electron microscope JEOL, JSM 35. The optical microscopic observations have shown that after annealing, a gray-black granular layer is formed on the cadmium sulphide single crystals and this layer can easily be separated from the crystal substrate. Under the granular layer the crystal is heavily damaged. The whiskers grow on the granular layer and they are coloured yellow-brown or red-brown. The maximum whisker length attains several hundreds of micrometres and in some cases up to 1 mm or more. (author)

Structural and electrical properties of nickel substituted cadmium ferrite

Science.gov (United States)

Chethan, B.; Raj Prakash, H. G.; Vijayakumari, S. C.; Ravikiran, Y. T.

2018-05-01

Spinal nano-sized Cadmium ferrite (CD) and Nickel substituted cadmium ferrite (NSCF) were fabricated by sol-gel auto combustion method. The formation of spinal structure of ferrite materials was confirmed by X-ray diffraction (XRD) analysis. The crystallites size of CF and NSCF as determined by Scherrer's formula were found to be 24.73 nm and 17.70 nm respectively. comparative study of Fourier transform infrared spectroscopy (FTIR) of CF and NSCF revealed tetrahedral absorption bands shifted slightly towards higher frequency where as octahedral bands shifted towards lower frequency side confirming interfacial interaction between Ni and CF. The AC conductivity (σ), loss tangent (tan δ) and complex plane impedance plots for both CF and NSCF are determined at various frequencies ranging from 50 kHz to 5 MHz and comparatively analyzed. The increase in AC conductivity of the NSCF nano particles as compared to CF was explained in the light of hopping model. The impedance measurement of NSCF show presence of a semi-circle corresponding to the grain boundary resistance and hence shows that the conductivity takes place largely through grain boundaries.

C-terminal KDEL-modified cystatin C is retained in transfected CHO cells

DEFF Research Database (Denmark)

Johansen, Teit Eliot; Vogel, Charlotte Katrine; Schwartz, Thue W.

1990-01-01

The significance of a C-terminal tetrapeptide, Lys-Asp-Glu-Leu (KDEL), as a retention signal for the endoplasmatic reticulum was studied using cystatin C, a general thiol protease inhibitor, as the reporter protein. Clones of CHO cells were analyzed after stable transfection with eukaryotic...

Cadmium accumulation and growth responses of a poplar (Populus deltoids x Populus nigra) in cadmium contaminated purple soil and alluvial soil

Energy Technology Data Exchange (ETDEWEB)

Wu Fuzhong [Faculty of Forestry, Sichuan Agricultural University, 625014, Ya' an (China); Yang Wanqin, E-mail: scyangwq@163.com [Faculty of Forestry, Sichuan Agricultural University, 625014, Ya' an (China); Zhang Jian; Zhou Liqiang [Faculty of Forestry, Sichuan Agricultural University, 625014, Ya' an (China)

2010-05-15

To characterize the phytoextraction efficiency of a hybrid poplar (Populus deltoids x Populus nigra) in cadmium contaminated purple soil and alluvial soil, a pot experiment in field was carried out in Sichuan basin, western China. After one growing period, the poplar accumulated the highest of 541.98 {+-} 19.22 and 576.75 {+-} 40.55 {mu}g cadmium per plant with 110.77 {+-} 12.68 and 202.54 {+-} 19.12 g dry mass in these contaminated purple soil and alluvial soil, respectively. Higher phytoextraction efficiency with higher cadmium concentration in tissues was observed in poplar growing in purple soil than that in alluvial soil at relative lower soil cadmium concentration. The poplar growing in alluvial soil had relative higher tolerance ability with lower reduction rates of morphological and growth characters than that in purple soil, suggesting that the poplar growing in alluvial soil might display the higher phytoextraction ability when cadmium contamination level increased. Even so, the poplars exhibited obvious cadmium transport from root to shoot in both soils regardless of cadmium contamination levels. It implies that this examined poplar can extract more cadmium than some hyperaccumulators. The results indicated that metal phytoextraction using the poplar can be applied to clean up soils moderately contaminated by cadmium in these purple soil and alluvial soil.

Emergence of rifampicin, tigecycline, and colistin-resistant Acinetobacter baumannii in Iran; spreading of MDR strains of novel International Clone variants.

Science.gov (United States)

Bahador, Abbas; Taheri, Mohammad; Pourakbari, Babak; Hashemizadeh, Zahra; Rostami, Hossein; Mansoori, Noormohamad; Raoofian, Reza

2013-10-01

Multidrug-resistant Acinetobacter baumannii infections are serious challenges for clinicians because of A. baumannii propensity to acquire resistance to a wide spectrum of antimicrobial agents. In this study, 91 A. baumannii isolates from patients in tertiary intensive care units of three university hospitals in the north, central, and south of Iran were selected and tested for susceptibility to 22 antimicrobials; amplified restriction fragment polymorphism and multiplex polymerase chain reaction methods were used to determine genetic relationships and International Clone (IC) of A. baumannii isolates, respectively. Twenty-four genotypes were identified in A. baumannii isolates. About 91.2% of isolates categorized into 4 distinct clusters; one was more heterogeneous and observed across the three locations. A considerable number of the isolates (27.5%) belonged to the novel IC variant, sequence group 7 (SG7), which was geographically widespread in three locations. The drug resistance pattern showed that 14.2%, 20%, and 77% of the A. baumannii isolates were resistant to colistin, tigecycline, and rifampicin, respectively. Nine percent of isolates (8) showed simultaneous resistance to colistin, rifampicin, and tigecycline. Interestingly, all of them were susceptible to ampicillin-sulbactam and/or tobramycin. According to our results, SG7 could be considered as a pan-Iranian clone.

Remediation of cadmium by Indian mustard (Brassica juncea L. from cadmium contaminated soil: a phytoextraction study

Directory of Open Access Journals (Sweden)

Rajeev Kumar Bhadkariya

2014-05-01

Full Text Available Cadmium is a toxic metal for living organisms and an environmental contaminant. Soils in many parts of the world are slightly too moderately contaminated by Cd due to long term use and disposal of Cd-contaminated wastes. Cost effective technologies are needed to remove cadmium from the contaminated sites. Soil phytoextraction is engineering based, low cost and socially accepted developing technology that uses plants to clean up contaminants in soils. This technology can be adopted as a remediation of cadmium from Cd-contaminated soils with the help of Brassica juncea plant. The objective of this work was to evaluate the cadmium (Cd accumulate and the tolerance of Brassica juncea. The Cd accumulates in all parts of plants (roots, stems and leaves. It was found that accumulating efficiency increased with the increase in the concentration of applied cadmium metal solution. Maximum accumulation of cadmium was found in roots than stem and leaves. Phytoextraction coefficient and translocation factor were highest to show the validity of the Brassica juncea species for hyperaccumulation of the Cd metal. These results suggested that Brassica juncea has a high ability to tolerate and accumulate Cd, so it might be a promising plant to be used for phytoextraction of Cd contaminated soil. DOI: http://dx.doi.org/10.3126/ije.v3i2.10533 International Journal of the Environment Vol.3(2 2014: 229-237

Influence of protein deficiency on cadmium toxicity in rats

Energy Technology Data Exchange (ETDEWEB)

Tewari, P C; Jain, V K; Ashquin, M; Tandon, S K

1986-07-01

The effects of a low protein diet on the body uptake and retention of cadmium, levels of essential trace elements, and cadmium-induced biochemical alterations in liver and kidneys of the rat were investigated. Low dietary protein disturbs cadmium induced alterations in carbohydrate metabolism, essential trace elements metabolism and offsets the hepatic and renal process of cadmium detoxification. Protein malnutrition enhances the susceptibility to cadmium intoxication.

Cadmium-related mortality and long-term secular trends in the cadmium body burden of an environmentally exposed population.

Science.gov (United States)

Nawrot, Tim S; Van Hecke, Etienne; Thijs, Lutgarde; Richart, Tom; Kuznetsova, Tatiana; Jin, Yu; Vangronsveld, Jaco; Roels, Harry A; Staessen, Jan A

2008-12-01

Few population studies have reported on the long-term changes in the internal cadmium dose and simultaneously occurring mortality. We monitored blood cadmium (BCd), 24-hr urinary cadmium (UCd), and mortality in an environmentally exposed population. Starting from 1985, we followed BCd (until 2003), UCd (until 1996), and mortality (until 2007) among 476 and 480 subjects, randomly recruited from low- exposure areas (LEA) and high-exposure areas (HEA). The last cadmium-producing plant in the HEA closed in 2002. From 1985-1989 to 1991-1996, BCd decreased by 40.3% and 18.9% in the LEA and HEA, respectively (p fashion without threshold.

Bioavailability of cadmium from linseed and cocoa

DEFF Research Database (Denmark)

Hansen, Max; Sloth, Jens Jørgen; Rasmussen, Rie Romme

In Denmark and EU the exposure of cadmium from food is at a level that is relatively close to the Tolerable Daily Intake (TDI). This report describes an investigation of the bioavailability of cadmium in selected food items known to contain high levels of cadmium. The purpose was to provide data...

Phytoremediation of cadmium and nickel by Spirodela polyrhiza

International Nuclear Information System (INIS)

Chaudhuri, Devaleena; Goswami, Chandrima; Chatterjee, Sumon; Majumder, Arunabha; Mishra, A.K.; Bandyopadhyay, Kaushik

2011-01-01

Heavy metal pollution in surface and groundwater has considerably increased in the last few years. It is essential to have an effective removal mechanism of these toxic metals. Current research includes the need to develop environment friendly and cost effective technologies for removing heavy metals from water. In several studies cadmium and nickel have been considerably removed using phytoremediation. The removal efficiency of cadmium and nickel by Spirodela polyrhiza, common duckweed has been examined in the present study for 3 different concentrations of cadmium (1, 2 and 3 mg/L) and nickel (4, 5 and 6 mg/L). Two sets of experiments for cadmium and nickel were conducted separately. Effect of metal toxicity on Spirodela polyrhiza was evaluated in terms of relative growth factor and cadmium was found to be more toxic than nickel. Under experimental condition BCF value for cadmium removal was more than >1000 in all the 3 concentrations of cadmium. But the BCF value was found to be more than > 1000 only when input nickel concentration was 4 mg/L during phytoremediation process. Experimental results suggest that Spirodela polyrhiza has the potential of accumulating cadmium and nickel from aqueous solution at lower metal concentration. (author)

29 CFR 1926.1127 - Cadmium.

Science.gov (United States)

2010-07-01

... occupational exposure to cadmium as follows: (1) Reassess the employee's work practices and personal hygiene... employee's work practices and personal hygiene; the employee's respirator use, if any; the employee's...; assuring that all employees exposed to air cadmium levels above the PEL wear appropriate personal...

Urinary N-acetyl-beta -D-glucosaminidase and its isoenzymes A & B in workers exposed to cadmium at cadmium plating

Directory of Open Access Journals (Sweden)

Rajan BK

2007-07-01

Full Text Available Abstract Objective The present study was carried out to determine the effect of cadmium exposure on Urinary N-acetyl-beta -D-glucosaminidase and its isoenzymes A and B in workers exposed at cadmium plating. Methods 50 subjects using cadmium during cadmium plating formed the study group. An equal number of age-sex matched subjects working in administrative section formed the control group. Urinary cadmium levels were determined by using a flameless atomic absorption spectrophotometer. Urinary N-acetyl-beta -D-glucosaminidase and its isoenzymes A and B were determined by using spectrophotmetric method. Results A significant increase of urinary total N-acetyl-beta -D-glucosaminidase and its isoenzymes A and B profiles were noted in study as compared to controls. The levels of urinary N-acetyl-beta -D-glucosaminidase and its isoenzymes A and B profiles were positively and significantly correlated with cadmium levels in urine. Multiple regression analysis was used to assess the effect of urinary cadmium or life style confounding factors (age, BMI, smoking and alcohol consumption on urinary N-acetyl-beta -D-glucosaminidase and its isoenzymes A and B. The analysis showed that the study subjects who had urine cadmium levels greater than 5 μg/g of creatinine, work duration >15 years, smoking and body mass index variables were significantly associated with urinary total N-acetyl-beta -D-glucosaminidase but not on isoenzymes A&B. Conclusion The results presented in this study shows that the increased levels of urinary N-acetyl-beta -D-glucosaminidase observed in cadmium-exposed workers could be used as biomarkers for suggesting preventive measure.

Prevalence of naturally occurring protease inhibitor resistance-associated variants in hemodialysis and renal transplant patients with hepatitis C virus infection.

Science.gov (United States)

Tavares, Rita C F; Feldner, Ana C C A; Pinho, João R R; Uehara, Silvia N O; Emori, Christini T; Carvalho-Filho, Roberto J; Silva, Ivonete S S; Santana, Rúbia A F; de Castro, Vanessa F D; Castoli, Gregório T F; Cristovão, Charliana U; Ferraz, Maria L C G

2017-07-01

Background NS3 protease inhibitors (PIs) were the first direct antiviral agents used for the treatment of hepatitis C virus. The combination of second-wave PIs with other direct antiviral agents enabled the use of interferon-free regimens for chronic kidney disease patients on dialysis and renal transplant (RTx) recipients, populations in which the use of interferon and ribavirin is limited. However, the occurrence of PI resistance-associated variants (RAVs), both baseline and induced by therapy, has resulted in the failure of many treatment strategies. Methods The aim of this study was to estimate the prevalence of PI RAVs and of the Q80K polymorphism in chronic kidney disease patients on hemodialysis and RTx recipients. Direct sequencing of the NS3 protease was performed in 67 patients (32 hemodialysis and 35 RTx).Results RAVs to PIs were detected in 18% of the patients: V55A (9%), V36L (1.5%), T54S (1.5%), S122N (1.5%), I170L (1.5%), and M175L (1.5%). Only 1.5% of the patients carried the Q80K polymorphism. The frequency of these mutations was more than two times higher in patients infected with GT1a (25%) than GT1b (9.7%) (P=0.1). The mutations were detected in 20% of treatment-naive patients and in 15.6% of peginterferon/ribavirin-experienced patients (P=0.64). Furthermore, no mutation that would confer high resistance to PIs was detected.Conclusion The Q80K polymorphism was rare in the population studied. The occurrence of RAVs was common, with predominance in GT1a. However, the variants observed were those associated with a low level of resistance to PIs, facilitating the use of these drugs in this special group of patients.

Response of Saccharomyces cerevisiae to cadmium stress

International Nuclear Information System (INIS)

Moreira, Luciana Mara Costa; Ribeiro, Frederico Haddad; Neves, Maria Jose; Porto, Barbara Abranches Araujo; Amaral, Angela M.; Menezes, Maria Angela B.C.; Rosa, Carlos Augusto

2009-01-01

The intensification of industrial activity has been greatly contributing with the increase of heavy metals in the environment. Among these heavy metals, cadmium becomes a serious pervasive environmental pollutant. The cadmium is a heavy metal with no biological function, very toxic and carcinogenic at low concentrations. The toxicity of cadmium and several other metals can be mainly attributed to the multiplicity of coordination complexes and clusters that they can form. Some aspects of the cellular response to cadmium were extensively investigated in the yeast Saccharomyces cerevisiae. The primary site of interaction between many toxic metals and microbial cells is the plasma membrane. Plasma-membrane permeabilisation has been reported in a variety of microorganisms following cadmium exposure, and is considered one mechanism of cadmium toxicity in the yeast. In this work, using the yeast strain S. cerevisiae W303-WT, we have investigated the relationships between Cd uptake and release of cellular metal ions (K + and Na + ) using neutron activation technique. The neutron activation was an easy, rapid and suitable technique for doing these metal determinations on yeast cells; was observed the change in morphology of the strains during the process of Cd accumulation, these alterations were observed by Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM) during incorporation of cadmium. (author)

Response of Saccharomyces cerevisiae to cadmium stress

Energy Technology Data Exchange (ETDEWEB)

Moreira, Luciana Mara Costa; Ribeiro, Frederico Haddad; Neves, Maria Jose [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Lab. de Radiobiologia], e-mail: luamatu@uol.com.br; Porto, Barbara Abranches Araujo; Amaral, Angela M.; Menezes, Maria Angela B.C. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Lab. de Ativacao Neutronica], e-mail: menezes@cdtn.br; Rosa, Carlos Augusto [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Microbiologia], e-mail: carlrosa@icb.ufmg

2009-07-01

The intensification of industrial activity has been greatly contributing with the increase of heavy metals in the environment. Among these heavy metals, cadmium becomes a serious pervasive environmental pollutant. The cadmium is a heavy metal with no biological function, very toxic and carcinogenic at low concentrations. The toxicity of cadmium and several other metals can be mainly attributed to the multiplicity of coordination complexes and clusters that they can form. Some aspects of the cellular response to cadmium were extensively investigated in the yeast Saccharomyces cerevisiae. The primary site of interaction between many toxic metals and microbial cells is the plasma membrane. Plasma-membrane permeabilisation has been reported in a variety of microorganisms following cadmium exposure, and is considered one mechanism of cadmium toxicity in the yeast. In this work, using the yeast strain S. cerevisiae W303-WT, we have investigated the relationships between Cd uptake and release of cellular metal ions (K{sup +} and Na{sup +}) using neutron activation technique. The neutron activation was an easy, rapid and suitable technique for doing these metal determinations on yeast cells; was observed the change in morphology of the strains during the process of Cd accumulation, these alterations were observed by Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM) during incorporation of cadmium. (author)

Epidemiological approach to cadmium pollution in Japan

Energy Technology Data Exchange (ETDEWEB)

Shigematsu, I.

1984-04-01

The study of health problems due to cadmium pollution in Japan originated from an endemic episode of Itai-itai disease in a rural area in north-central Japan after World War II. The disease was defined as osteomalacia with tubular changes in the kidney and considered to be associated with excess intake of cadmium. This episode motivated the Japanese Government to conduct health examinations on the general population in cadmium-polluted and non-polluted areas throughout the country since 1969. Although Itai-itai disease-like bone changes were rarely found, these studies revealed a higher prevalence of renal tubular dysfunction among elderly people in the cadmium-polluted areas. No significant difference was noted in cancer mortality, but mortality from cardiovascular diseases and all causes tended to be lower in cadmium-polluted areas. Clinical and pathological studies in man as well as experiments on primates have recently been made to elucidate the pathogenesis of Itai-itai disease and the health effects of cadmium. The lack of knowledge on the ecological and biological complex of cadmium resulted in the impediment of studies on this problem. The lesson from this experience is that basic research is essential for promoting the study of pollutants such as heavy metals, though pollution problems usually require urgent solutions.

Sources of cadmium exposure among healthy premenopausal women

Energy Technology Data Exchange (ETDEWEB)

Adams, Scott V., E-mail: sadams@fhcrc.org [Fred Hutchinson Cancer Research Center, PO Box 19024, M4-B402, Seattle, WA 98109 (United States); Department of Epidemiology, University of Washington, Box 357236, Seattle, WA 98195 (United States); Newcomb, Polly A. [Fred Hutchinson Cancer Research Center, PO Box 19024, M4-B402, Seattle, WA 98109 (United States); Department of Epidemiology, University of Washington, Box 357236, Seattle, WA 98195 (United States); Shafer, Martin M. [Environmental Chemistry and Technology Program, University of Wisconsin and Wisconsin State Laboratory of Hygiene, Madison, WI (United States); Atkinson, Charlotte [Department of Oral and Dental Science, Bristol Dental School, Bristol (United Kingdom); Bowles, Erin J. Aiello [Group Health Research Institute, Seattle, WA (United States); Newton, Katherine M. [Department of Epidemiology, University of Washington, Box 357236, Seattle, WA 98195 (United States); Group Health Research Institute, Seattle, WA (United States); Lampe, Johanna W. [Fred Hutchinson Cancer Research Center, PO Box 19024, M4-B402, Seattle, WA 98109 (United States); Department of Epidemiology, University of Washington, Box 357236, Seattle, WA 98195 (United States)

2011-04-01

Background: Cadmium, a persistent and widespread environmental pollutant, has been associated with kidney function impairment and several diseases. Cigarettes are the dominant source of cadmium exposure among smokers; the primary source of cadmium in non-smokers is food. We investigated sources of cadmium exposure in a sample of healthy women. Methods: In a cross-sectional study, 191 premenopausal women completed a health questionnaire and a food frequency questionnaire. The cadmium content of spot urine samples was measured with inductively-coupled plasma mass spectrometry and normalized to urine creatinine content. Multivariable linear regression was used to estimate the strength of association between smoking habits and, among non-smokers, usual foods consumed and urinary cadmium, adjusted for age, race, multivitamin and supplement use, education, estimated total energy intake, and parity. Results: Geometric mean urine creatinine-normalized cadmium concentration (uCd) of women with any history of cigarette smoking was 0.43 {mu}g/g (95% confidence interval (CI): 0.38-0.48 {mu}g/g) and 0.30 {mu}g/g (0.27-0.33 {mu}g/g) among never-smokers, and increased with pack-years of smoking. Analysis of dietary data among women with no reported history of smoking suggested that regular consumption of eggs, hot cereals, organ meats, tofu, vegetable soups, leafy greens, green salad, and yams was associated with uCd. Consumption of tofu products showed the most robust association with uCd; each weekly serving of tofu was associated with a 22% (95% CI: 11-33%) increase in uCd. Thus, uCd was estimated to be 0.11 {mu}g/g (95% CI: 0.06-0.15 {mu}g/g) higher among women who consumed any tofu than among those who consumed none. Conclusions: Cigarette smoking is likely the most important source of cadmium exposure among smokers. Among non-smokers, consumption of specific foods, notably tofu, is associated with increased urine cadmium concentration. - Research highlights: {yields

Sources of cadmium exposure among healthy premenopausal women

International Nuclear Information System (INIS)

Adams, Scott V.; Newcomb, Polly A.; Shafer, Martin M.; Atkinson, Charlotte; Bowles, Erin J. Aiello; Newton, Katherine M.; Lampe, Johanna W.

2011-01-01

Background: Cadmium, a persistent and widespread environmental pollutant, has been associated with kidney function impairment and several diseases. Cigarettes are the dominant source of cadmium exposure among smokers; the primary source of cadmium in non-smokers is food. We investigated sources of cadmium exposure in a sample of healthy women. Methods: In a cross-sectional study, 191 premenopausal women completed a health questionnaire and a food frequency questionnaire. The cadmium content of spot urine samples was measured with inductively-coupled plasma mass spectrometry and normalized to urine creatinine content. Multivariable linear regression was used to estimate the strength of association between smoking habits and, among non-smokers, usual foods consumed and urinary cadmium, adjusted for age, race, multivitamin and supplement use, education, estimated total energy intake, and parity. Results: Geometric mean urine creatinine-normalized cadmium concentration (uCd) of women with any history of cigarette smoking was 0.43 μg/g (95% confidence interval (CI): 0.38-0.48 μg/g) and 0.30 μg/g (0.27-0.33 μg/g) among never-smokers, and increased with pack-years of smoking. Analysis of dietary data among women with no reported history of smoking suggested that regular consumption of eggs, hot cereals, organ meats, tofu, vegetable soups, leafy greens, green salad, and yams was associated with uCd. Consumption of tofu products showed the most robust association with uCd; each weekly serving of tofu was associated with a 22% (95% CI: 11-33%) increase in uCd. Thus, uCd was estimated to be 0.11 μg/g (95% CI: 0.06-0.15 μg/g) higher among women who consumed any tofu than among those who consumed none. Conclusions: Cigarette smoking is likely the most important source of cadmium exposure among smokers. Among non-smokers, consumption of specific foods, notably tofu, is associated with increased urine cadmium concentration. - Research highlights: →Urine cadmium, usual

Separation of cadmium from solutions containing high concentration of zinc ions

International Nuclear Information System (INIS)

Sharma, K.D.; Bhutani, A.K.; Parvathisem, P.

1984-01-01

In hydrometallurgical process of extracting cadmium as a byproduct, zinc dust is added for separation of cadmium as cadimum sponge. High amounts of zinc are quite often noticed in the cadmium electrolyte subjected for electrowinning of the metal. This leads to poor quality of cadmium deposit and lower current efficiencies. Study of cadmium sponge cementation process revealed that zinc dust may be added to an acidic cadmium solution for precipitation of cadmium sponge without neutralization of the free acidity present in the system. This fact is utilized for obtaining a high cadmium sponge with 75-80 per cent cadmium and 5-10 per cent zinc with 98 per cent recovery of cadmium from the solution as sponge. The suggested process is confirmed in a cadmium production plant producing 11.0 MT of cadmium per month. (author)

Fuel conditioning facility electrorefiner cadmium vapor trap operation

International Nuclear Information System (INIS)

Vaden, D. E.

1998-01-01

Processing sodium-bonded spent nuclear fuel at the Fuel Conditioning Facility at Argonne National Laboratory-West involves an electrometallurgical process employing a molten LiCl-KCl salt covering a pool of molten cadmium. Previous research has shown that the cadmium dissolves in the salt as a gas, diffuses through the salt layer and vaporizes at the salt surface. This cadmium vapor condenses on cool surfaces, causing equipment operation and handling problems. Using a cadmium vapor trap to condense the cadmium vapors and reflux them back to the electrorefiner has mitigated equipment problems and improved electrorefiner operations

Effect of cadmium salts on some growth and metabolic activities of selected fungi from the rhizosphere of Glycine max and Zea mays

Energy Technology Data Exchange (ETDEWEB)

Naguib, M.I.; Ali, M.I.; Haikal, N.Z.; Sharaf, E.F. (Cairo Univ. (Egypt))

1986-12-01

Six fungi, isolated from the rhizosphere of Glycine max and Zea Mays, were selected for their variable resistance to soil application of cadmium nitrate and cadmium sulfate, at the range of 100-1000 ppm concentration. These were (a) Aspergillus terreus and Rhizopus oryzae; (b) Paecilomyces divaricata, Curvularia tetramera; (c) Fusarium oxysporum and (d) Cladosporium herbarum. Fifty ppm cadmium salts exerted no effect on spore germination of R. oryzae, F. oxysporum or C. tetramera, stimulated A. terreus and P. divaricata and suppressed C. herbarum. 100 ppm dose exerted variable effects dependent on the organism and/or accompanying anion. 1000 ppm cadmium arrested spore germination of all the tested fungi except F. oxysporum where marked suppression were observed. Cadmium arrested growth of C. herbarum and P. divaricata at 50 ppm, initiated that of A. terreus, C. tetramera and F. oxysporum but seemed without effect on R. oryzae. Larger doses seemed to be inhibitory to all organisms, R. oryzae being least affected. Results show that nitrogen secretion was not a function of tolerance of the fungi to cadmium applied to the soil but was largely controlled by the effect of cadmium on the permeability of the cells of each individual fungus. Cadmium seemed to stimulate nitrogen metabolism of Aspergillus and Fusarium, had little or no effect on that of Rhizopus but suppressed that of Curvularia. Most accumulated nitrogen was in the form of amino and other soluble nitrogen. Cadmium inhibited the incorporation of absorbed phosphorus into energy-rich compounds. This was concomitant with the failure of amino acid incorporation into proteins.

Enzyme activities and antibiotic susceptibility of colonial variants of Bacillus subtilis and Bacillus licheniformis.

OpenAIRE

Carlisle, G E; Falkinham, J O

1989-01-01

A nonmucoid colonial variant of a mucoid Bacillus subtilis strain produced less amylase activity and a transparent colonial variant of a B. licheniformis strain produced less protease activity compared with their parents. Antibiotic susceptibility patterns of the colonial variants differed, and increased resistance to beta-lactam antibiotics was correlated with increased production of extracellular beta-lactamase.

Cadmium accumulation and growth responses of a poplar (Populus deltoids x Populus nigra) in cadmium contaminated purple soil and alluvial soil

International Nuclear Information System (INIS)

Wu Fuzhong; Yang Wanqin; Zhang Jian; Zhou Liqiang

2010-01-01

To characterize the phytoextraction efficiency of a hybrid poplar (Populus deltoids x Populus nigra) in cadmium contaminated purple soil and alluvial soil, a pot experiment in field was carried out in Sichuan basin, western China. After one growing period, the poplar accumulated the highest of 541.98 ± 19.22 and 576.75 ± 40.55 μg cadmium per plant with 110.77 ± 12.68 and 202.54 ± 19.12 g dry mass in these contaminated purple soil and alluvial soil, respectively. Higher phytoextraction efficiency with higher cadmium concentration in tissues was observed in poplar growing in purple soil than that in alluvial soil at relative lower soil cadmium concentration. The poplar growing in alluvial soil had relative higher tolerance ability with lower reduction rates of morphological and growth characters than that in purple soil, suggesting that the poplar growing in alluvial soil might display the higher phytoextraction ability when cadmium contamination level increased. Even so, the poplars exhibited obvious cadmium transport from root to shoot in both soils regardless of cadmium contamination levels. It implies that this examined poplar can extract more cadmium than some hyperaccumulators. The results indicated that metal phytoextraction using the poplar can be applied to clean up soils moderately contaminated by cadmium in these purple soil and alluvial soil.

Fed-batch CHO cell culture for lab-scale antibody production

DEFF Research Database (Denmark)

Fan, Yuzhou; Ley, Daniel; Andersen, Mikael Rørdam

2017-01-01

Fed-batch culture is the most commonly used upstream process in industry today for recombinant monoclonal antibody production using Chinese hamster ovary cells. Developing and optimizing this process in the lab is crucial for establishing process knowledge, which enable rapid and predictable tech......-transfer to manufacturing scale. In this chapter, we will describe stepwise how to carry out fed-batch CHO cell culture for lab-scale antibody production....

2-Aminoanthracene, 5-fluorouracil, colchicine, benzo[a]pyrene, cadmium chloride and cytosine arabinoside tested in the in vitro mammalian cell micronucleus test (MNvit) in Chinese hamster ovary (CHO) cells at Covance Laboratories, Harrogate UK in support of OECD draft Test Guideline 487.

Science.gov (United States)

Whitwell, James; Fowler, Paul; Allars, Sarah; Jenner, Karen; Lloyd, Melvyn; Wood, Debbie; Smith, Katie; Young, Jamie; Jeffrey, Laura; Kirkland, David

2010-10-29

The reference genotoxic agents 2-aminoanthracene (a metabolism dependent weak clastogen), 5-fluorouracil (a nucleoside analogue, characterised by a steep dose response profile), colchicine (an aneugen that inhibits tubulin polymerisation), benzo[a]pyrene (a polycyclic aromatic hydrocarbon requiring metabolic activation), cadmium chloride (an inorganic carcinogen), and cytosine arabinoside (a nucleoside analogue that inhibits the gap-filling step of excision repair) were tested in the in vitro micronucleus assay using the Chinese hamster ovary (CHO) cell line at Covance Laboratories, Harrogate, UK. All chemicals were treated in the absence and presence of cytokinesis block (via addition of cytochalasin B) with this work forming part of a collaborative evaluation of the toxicity measures recommended in the draft OECD Test Guideline 487 on the In vitro Mammalian Cell Micronucleus Test (MNvit). The toxicity measures used, detecting a possible combination of both cytostasis and cell death (though not cell death directly), were relative population doubling, relative increase in cell counts and relative cell counts for treatments in the absence of cytokinesis block, and replication index in the presence of cytokinesis block. All of the chemicals tested either gave marked positive increases in the percentage of micronucleated cells with and without cytokinesis block, or did not induce micronuclei at concentrations giving approximately 50-60% toxicity (cytostasis and cell death) or less by all of the toxicity measures used. The outcome from this series of tests supports the use of relative increase in cell counts and relative population doubling, as well as relative cell counts, as appropriate measures of cytotoxicity for the non-cytokinesis blocked in vitro micronucleus assay. Copyright © 2010 Elsevier B.V. All rights reserved.

Use of cadmium sulphide to measure integrated dose in short-time irradiation

International Nuclear Information System (INIS)

Nimnual, S.

1975-01-01

An experiment was made to measure the dose from a short burst of X-rays in the order of 1 second or less by means of the cadmium sulphide photoconductive cell. If protected from light, the CdS cell has a very high resistance such that it does not discharge a capacitor appreciably. But during irradiation, the resistance decreases temporarily and an amount of charge will leak from the capacitor through the Ca S cell. The result to this experiment shows that the principle works very well but it is necessary to add another fixed high resistance of about 10 7 ohms into the circuit in order to get results independent of the dose-rate. The equipment used in this experiment can measure a dose as low as 6 m R

Cadmium inhibits repair of UV-, methyl methanesulfonate- and N-methyl-N-nitrosourea-induced DNA damage in Chinese hamster ovary cells

International Nuclear Information System (INIS)

Fatur, Tanja; Lah, Tamara T.; Filipic, Metka

2003-01-01

The co-genotoxic effects of cadmium are well recognized and it is assumed that most of these effects are due to the inhibition of DNA repair. We used the comet assay to analyze the effect of low, non-toxic concentrations of CdCl 2 on DNA damage and repair-induced in Chinese hamster ovary (CHO) cells by UV-radiation, by methyl methanesulfonate (MMS) and by N-methyl-N-nitrosourea (MNU). The UV-induced DNA lesions revealed by the comet assay are single-strand breaks which are the intermediates formed during nucleotide excision repair (NER). In cells exposed to UV-irradiation alone the formation of DNA strand breaks was rapid, followed by a fast rejoining phase during the first 60 min after irradiation. In UV-irradiated cells pre-exposed to CdCl 2 , the formation of DNA strand breaks was significantly slower, indicating that cadmium inhibited DNA damage recognition and/or excision. Methyl methanesulfonate and N-methyl-N-nitrosourea directly alkylate nitrogen and oxygen atoms of DNA bases. The lesions revealed by the comet assay are mainly breaks at apurinic/apyrimidinic (AP) sites and breaks formed as intermediates during base excision repair (BER). In MMS treated cells the initial level of DNA strand breaks did not change during the first hour of recovery; thereafter repair was detected. In cells pre-exposed to CdCl 2 the MMS-induced DNA strand breaks accumulated during the first 2 h of recovery, indicating that AP sites and/or DNA strand breaks were formed but that further steps of BER were blocked. In MNU treated cells the maximal level of DNA strand breaks was detected immediately after the treatment and the breaks were repaired rapidly. In CdCl 2 pre-treated cells the formation of MNU-induced DNA single-strand breaks was not affected, while the repair was slower, indicating inhibition of polymerization and/or the ligation step of BER. Cadmium thus affects the repair of UV-, MMS- and MNU-induced DNA damage, providing further evidence, that inhibition of DNA repair

Cadmium verification measurements of HFIR shroud assembly 22

International Nuclear Information System (INIS)

Chapman, J.A.; Schultz, F.J.

1994-04-01

This report discusses radiation-based nondestructive examination methods which have been used to successfully verify the presence of cadmium in High Flux Isotope Reactor (HFIR) spent-fuel shroud assembly number 22 (SA22). These measurements show, in part, that SA22 is certified to meet the criticality safety specifications for a proposed reconfiguration of the HFIR spent-fuel storage array. Measurement of the unique 558.6-keV gamma-ray from neutron radiative capture on cadmium provided conclusive evidence for the presence of cadmium in the outer shroud of the assembly. Cadmium verification in the center post and outer shroud was performed by measuring the degree of neutron transmission in SA22 relative to two calibration shroud assemblies. Each measurement was performed at a single location on the center post and outer shroud. These measurements do not provide information on the spatial distribution or uniformity of cadmium within an assembly. Separate measurements using analog and digital radiography were performed to (a) globally map the continuity of cadmium internal mass, and (b) locally determine the thickness of cadmium. Radiography results will be reported elsewhere. The measurements reported here should not be used to infer the thickness of cadmium in either the center post or outer shroud of an assembly

Dual effect of insulin resistance and cadmium on human granulosa cells - In vitro study

Energy Technology Data Exchange (ETDEWEB)

Belani, Muskaan, E-mail: muskaanbelani@gmail.com [Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara 390 002, Gujarat, India. (India); Shah, Preeti, E-mail: preeti.shah@novaivifertility.com [Nova IVI Fertility, Behind Xavier' s Ladies Hostel, 108, Swastik Society Rd., Navrangpura, Ahmedabad 390009, Gujarat, India. (India); Banker, Manish, E-mail: manish.banker@novaivifertility.com [Nova IVI Fertility, Behind Xavier' s Ladies Hostel, 108, Swastik Society Rd., Navrangpura, Ahmedabad 390009, Gujarat, India. (India); Gupta, Sarita, E-mail: saritagupta9@gmail.com [Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara 390 002, Gujarat, India. (India)

2016-12-15

Combined exposure of cadmium (Cd) and insulin resistance (IR) might be responsible for subfertility. In the present study, we investigated the effects of Cd in vitro in IR human granulosa cells. Isolated human granulosa cells from control and polycystic ovary syndrome (PCOS) follicular fluid samples were confirmed for IR by decrease in protein expression of insulin receptor-β. Control and IR human granulosa cells were then incubated with or without 32 μM Cd. The combined effect of IR with 32 μM Cd in granulosa cells demonstrated significant decrease in expression of StAR, CYP11A1, CYP19A1, 17β-HSD, 3β-HSD, FSH-R and LH-R. Decrease was also observed in progesterone and estradiol concentrations as compared to control. Additionally, increase in protein expression of cleaved PARP-F2, active caspase-3 and a positive staining for Annexin V and PI indicated apoptosis as the mode of increased cell death ultimately leading to decreased steroidogenesis, as observed through the combined exposure. Taken together the results suggest decrease in steroidogenesis ultimately leading to abnormal development of the follicle thus compromising fertility at the level of preconception. - Highlights: • Protein expression of INSR-β in granulosa cells to differentiate PCOS-IR and NIR • Cd and IR together decrease steroidogenesis in human granulosa cells in vitro. • Cd and IR increase human granulosa cell death by increase in apoptosis. • Environment and life style are set to hamper pregnancies at preconception level.

Dual effect of insulin resistance and cadmium on human granulosa cells - In vitro study

International Nuclear Information System (INIS)

Belani, Muskaan; Shah, Preeti; Banker, Manish; Gupta, Sarita

2016-01-01

Combined exposure of cadmium (Cd) and insulin resistance (IR) might be responsible for subfertility. In the present study, we investigated the effects of Cd in vitro in IR human granulosa cells. Isolated human granulosa cells from control and polycystic ovary syndrome (PCOS) follicular fluid samples were confirmed for IR by decrease in protein expression of insulin receptor-β. Control and IR human granulosa cells were then incubated with or without 32 μM Cd. The combined effect of IR with 32 μM Cd in granulosa cells demonstrated significant decrease in expression of StAR, CYP11A1, CYP19A1, 17β-HSD, 3β-HSD, FSH-R and LH-R. Decrease was also observed in progesterone and estradiol concentrations as compared to control. Additionally, increase in protein expression of cleaved PARP-F2, active caspase-3 and a positive staining for Annexin V and PI indicated apoptosis as the mode of increased cell death ultimately leading to decreased steroidogenesis, as observed through the combined exposure. Taken together the results suggest decrease in steroidogenesis ultimately leading to abnormal development of the follicle thus compromising fertility at the level of preconception. - Highlights: • Protein expression of INSR-β in granulosa cells to differentiate PCOS-IR and NIR • Cd and IR together decrease steroidogenesis in human granulosa cells in vitro. • Cd and IR increase human granulosa cell death by increase in apoptosis. • Environment and life style are set to hamper pregnancies at preconception level.

Minimizing transfusion requirements for children undergoing craniosynostosis repair: the CHoR protocol.

Science.gov (United States)

Vega, Rafael A; Lyon, Camila; Kierce, Jeannette F; Tye, Gary W; Ritter, Ann M; Rhodes, Jennifer L

2014-08-01

Children with craniosynostosis may require cranial vault remodeling to prevent or relieve elevated intracranial pressure and to correct the underlying craniofacial abnormalities. The procedure is typically associated with significant blood loss and high transfusion rates. The risks associated with transfusions are well documented and include transmission of infectious agents, bacterial contamination, acute hemolytic reactions, transfusion-related lung injury, and transfusion-related immune modulation. This study presents the Children's Hospital of Richmond (CHoR) protocol, which was developed to reduce the rate of blood transfusion in infants undergoing primary craniosynostosis repair. A retrospective chart review of pediatric patients treated between January 2003 and Febuary 2012 was performed. The CHoR protocol was instituted in November 2008, with the following 3 components; 1) the use of preoperative erythropoietin and iron therapy, 2) the use of an intraoperative blood recycling device, and 3) acceptance of a lower level of hemoglobin as a trigger for transfusion (protocol implementation served as controls. A total of 60 children were included in the study, 32 of whom were treated with the CHoR protocol. The control (C) and protocol (P) groups were comparable with respect to patient age (7 vs 8.4 months, p = 0.145). Recombinant erythropoietin effectively raised the mean preoperative hemoglobin level in the P group (12 vs 9.7 g/dl, p protocol that includes preoperative administration of recombinant erythropoietin, intraoperative autologous blood recycling, and accepting a lower transfusion trigger significantly decreased transfusion utilization (p < 0.001). A decreased length of stay (p < 0.001) was seen, although the authors did not investigate whether composite transfusion complication reductions led to better outcomes.

Effects of cadmium on the biochemical composition of the freshwater crayfish Procambarus clarkii (Girard, 1852)

Energy Technology Data Exchange (ETDEWEB)

Torreblanca, A.; Del Ramo, J.; Diaz-Mayans, J. (Univ. of Valencia (Spain))

1991-12-01

Lake Albufera of Valencia (Spain) and the surrounding rice field waters are subjected to very heavy loads of sewage and toxic residues. Among these residues include heavy metals which have been deposited from the many urban and waste waters in this area. The American red crayfish, Procambarus clarkii from Albufera Lake has high resistance to heavy metals. The authors have also found that P. clarkii shows a high capacity for cadmium accumulation in experimental conditions and natural conditions since crayfish collected in this area contained considerable amounts of cadmium in several tissues even after 15 days of depuration in clean water. Since the physiological changes that take place when organisms are exposed to sublethal levels of stress could include rate of feeding as well as respiration and excretion, the net result could be a change in energy available for growth and reproduction. In this work, the authors have studied the biochemical energy composition of hepatopancreas, muscle and gills of P. clarkii after short term sublethal exposure to cadmium.

Engineering CHO cells with an oncogenic KIT improves cells growth, resilience to stress, and productivity.

Science.gov (United States)

Mahameed, Mohamed; Tirosh, Boaz

2017-11-01

An optimized biomanufacturing process in mammalian cells is contingent on the ability of the producing cells to reach high viable cell densities. In addition, at the peak of growth, cells need to continue producing the biological entity at a consistent quality. Thus, engineering cells with robust growth performance and resilience to variable stress conditions is highly desirable. The tyrosine kinase receptor, KIT, plays a key role in cell differentiation and the survival of several immune cell types. Its oncogenic mutant, D816V, endows cells with high proliferation capacity, and resistance to kinase inhibitors. Importantly, this onco-KIT mutant when introduced into various cell types is arrested in the endoplasmic reticulum in a constitutively active form. Here, we investigated the effect of oncogenic D816V KIT on the performance of CHO-K1 cells under conventional tissue culture growth settings and when adapted, to shaking conditions. The onco-KIT promoted global protein synthesis, elevated the expression of a secretable transgene, enhanced proliferation, and improved the overall titers of a model glycoprotein. Moreover, the expression of the onco-KIT endowed the cells with a remarkable resistance to various stress conditions. Our data suggest that the introduction of onco-KIT can serve as a strategy for improving glycoprotein biomanufacturing. Biotechnol. Bioeng. 2017;114: 2560-2570. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Liquid scintillation counting analysis of cadmium-109

International Nuclear Information System (INIS)

Robinson, M.K.; Barfuss, D.W.

1991-01-01

Recently the authors have used radiolabled cadmium-109 to measure the transport of inorganic cadmium in renal proximal tubules. An anomaly discovered in the liquid scintillation counting analysis of Cd-109 which is not attributable to normal decay; it consists of a significant decrease in the measured count rate of small amounts of sample. The objective is to determine whether the buffer solution used in the membrane transport studies is causing precipitation of the cadmium or whether cadmium is being adsorbed by the glass. It was important to determine whether the procedure could be modified to correct this problem. The problem does not appear to be related to the use of the buffer or to adsorption of Cd onto glass. Correction based on using triated L-glucose in all of these experiments and calculating a correction factor for the concentration of cadmium

Effects of diethyldithiocarbamate on the toxicokinetics of cadmium chloride in mice

DEFF Research Database (Denmark)

Andersen, O; Nielsen, J B

1989-01-01

Diethyldithiocarbamate (DDC) efficiently alleviates the acute toxicity of injected cadmium chloride, but enhances the acute toxicity of orally administered cadmium chloride. Further, DDC induces extensive changes in organ distribution of cadmium, and mobilizes aged cadmium depots. The present study...... investigates effects of DDC on the toxicokinetics of cadmium at lower doses of cadmium than those used in previous studies. During single exposure to subtoxic oral doses of cadmium chloride DDC enhanced intestinal cadmium absorption, both after intraperitoneal and oral administration of DDC. In such acute...... exposure experiments orally administered DDC only slightly changed the relative organ distribution of absorbed cadmium, while intraperitoneal administration of DDC induced extensive changes in organ preference of absorbed cadmium. The relative hepatic and testicular deposition was reduced, while...

Relation of the Allelic Variants of Multidrug Resistance Gene to Agranulocytosis Associated With Clozapine.

Science.gov (United States)

Anıl Yağcioğlu, A Elif; Yoca, Gökhan; Ayhan, Yavuz; Karaca, R Özgür; Çevik, Lokman; Müderrisoğlu, Ahmet; Göktaş, Mustafa T; Eni, Nurhayat; Yazıcı, M Kâzım; Bozkurt, Atilla; Babaoğlu, Melih O

2016-06-01

Clozapine use is associated with leukopenia and more rarely agranulocytosis, which may be lethal. The drug and its metabolites are proposed to interact with the multidrug resistance transporter (ABCB1/MDR1) gene product, P-glycoprotein (P-gp). Among various P-glycoprotein genetic polymorphisms, nucleotide changes in exons 26 (C3435T), 21 (G2677T), and 12 (C1236T) have been implicated for changes in pharmacokinetics and pharmacodynamics of many substrate drugs. In this study, we aimed to investigate the association between these specific ABCB1 polymorphisms and clozapine-associated agranulocytosis (CAA). Ten patients with a history of CAA and 91 control patients without a history of CAA, despite 10 years of continuous clozapine use, were included. Patient recruitment and blood sample collection were conducted at the Hacettepe University Faculty of Medicine, Department of Psychiatry, in collaboration with the members of the Schizophrenia and Other Psychotic Disorders Section of the Psychiatric Association of Turkey, working in various psychiatry clinics. After DNA extraction from peripheral blood lymphocytes, genotyping was performed using polymerase chain reaction and endonuclease digestion. Patients with CAA had shorter duration of clozapine use but did not show any significant difference in other clinical, sociodemographic characteristics and in genotypic or allelic distributions of ABCB1 variants and haplotypes compared with control patients. Among the 10 patients with CAA, none carried the ABCB1 all-variant haplotype (TT-TT-TT), whereas the frequency of this haplotype was approximately 12% among the controls. Larger sample size studies and thorough genetic analyses may reveal both genetic risk and protective factors for this serious adverse event.

Selection of chemically defined media for CHO cell fed-batch culture processes

NARCIS (Netherlands)

Pan, X.; Streefland, M.; Dalm, C.; Wijffels, R.H.; Martens, D.E.

2017-01-01

Two CHO cell clones derived from the same parental CHOBC cell line and producing the same monoclonal antibody (BC-G, a low producing clone; BC-P, a high producing clone) were tested in four basal media in all possible combinations with three feeds (=12 conditions) in fed-batch cultures.
Higher

Cadmium affects the social behaviour of rainbow trout, Oncorhynchus mykiss

International Nuclear Information System (INIS)

Sloman, Katherine A.; Scott, Graham R.; Diao Zhongyu; Rouleau, Claude; Wood, Chris M.; McDonald, D. Gord

2003-01-01

The present study investigated both the effects of cadmium on the social interactions of rainbow trout and the differential accumulation of waterborne cadmium among social ranks of fish. Fish exposed to waterborne cadmium concentrations of 2 μg l -1 for 24 h, followed by a 1, 2 or 3 day depuration period in clean water, had a decreased ability to compete with non-exposed fish. However, the competitive ability of exposed fish given a 5 day depuration period was not significantly impaired. Cadmium accumulated in the olfactory apparatus of fish exposed to waterborne cadmium for 24 h and decreased significantly only after 5 days depuration in clean water. Among groups of ten fish held in stream tanks, where all fish were exposed to cadmium, there were significant effects on social behaviour and growth rate. Dominance hierarchies formed faster among fish exposed to cadmium than among control fish, and overall growth rates were higher in the cadmium treatment. In groups of ten fish, social status also affected tissue accumulation of cadmium during waterborne exposure, with dominant fish accumulating more cadmium at the gill. In conclusion, exposure to low levels of cadmium, affects the social behaviour of fish, in part due to accumulation in the olfactory apparatus, and dominant fish accumulate more gill cadmium than subordinates during chronic waterborne exposure

Cadmium in milk and mammary gland in rats and mice

International Nuclear Information System (INIS)

Petersson Grawe, K.; Oskarsson, A.

2000-01-01

The purpose of the present investigation was to study the uptake of cadmium in mammary tissue, effects on milk secretion and composition, and lactational transport of cadmium to the sucklings. Cadmium exposure during lactation resulted in retention of cadmium in the mammary tissue in mice and rats. The uptake of cadmium in the mammary tissue was rapid, as shown in lactating mice by whole-body autoradiography 4 h after an intravenous injection of a tracer dose of 109 CdCl 2 . Retention of cadmium in kidneys of suckling pups was observed in the autoradiograms at 7 days after exposure of the dams. Lactating rats were intravenously infused with 109 CdCl 2 in 0.9% saline via osmotic minipumps from day 3 to day 16 after parturition. The cadmium dose given was 0, 8.8, 62 and 300 μg Cd/kg body wt. per day. Plasma and milk were collected at day 10 and 16 after parturition. Plasma cadmium levels in dams increased from day 10 to day 16. Cadmium levels were higher in milk than in plasma, with milk/plasma ratios varying from 2 to 6. Zinc levels in milk were positively correlated to cadmium levels in milk (r 2 =0.26; P=0.03). In milk, 109 Cd was distributed in fat (46-52%), casein fraction (40-46%), and whey fraction (6-8%). There was a high correlation between cadmium concentrations in pups' kidney and cadmium concentrations in dam's milk (r 2 =0.98; P 109 Cd was bound to metallothionein in mammary tissue. The fraction of radiolabelled cadmium bound to metallothionein increased in a dose-dependent manner in both the liver (88-98%) and mammary tissue (57-80%). The present results indicate a low transfer of cadmium to the suckling pup, which might be due to binding of cadmium to metallothionein in the mammary tissue. However, during the susceptible developmental period even a low cadmium exposure may be of concern. (orig.)

Effects of Aluminium Sulfate on Cadmium Accumulation in Rice

International Nuclear Information System (INIS)

Khamvarn, Vararas; Boontanon, Narin; Prapagdee, Benjaphorn; Kumsopa, Acharaporn; Boonsirichai, Kanokporn

2011-06-01

Full text: Cadmium accumulation in Pathum Thani 1 and Suphan Buri 60 rice cultivars was investigated upon treatment with aluminium sulfate as a precipitant. Rice was grown hydroponically in a medium containing 4 ppm cadmium nitrate with or without 4 ppm aluminium sulfate. Root, stem with leaves and grain samples were collected and analyzed for cadmium content using atomic absorption spectroscopy and inductively coupled plasma atomic emission spectroscopy. Without the addition of aluminium sulfate, Pathum Thani 1 and Suphan Buri 60 accumulated 24.71∫ 3.14 ppm and 34.43 ∫ 4.51 ppm (dry weight of whole plant) of cadmium, respectively. With aluminium sulfate, cadmium accumulation increased to 40.66 ∫ 2.47 ppm and 62.94 ∫ 10.69 ppm, respectively. The addition of aluminium sulfate to the planting medium did not reduce cadmium accumulation but caused the rice to accumulate more cadmium especially in the shoots and grains. This observation might serve as the basis for future research on the management of agricultural areas that are contaminated with cadmium and aluminium

Biological monitoring results for cadmium exposed workers.

Science.gov (United States)

McDiarmid, M A; Freeman, C S; Grossman, E A; Martonik, J

1996-11-01

As part of a settlement agreement with the Occupational Safety and Health Administration (OSHA) involving exposure to cadmium (Cd), a battery production facility provided medical surveillance data to OSHA for review. Measurements of cadmium in blood, cadmium in urine, and beta 2-microglobulin in urine were obtained for more than 100 workers over an 18-month period. Some airborne Cd exposure data were also made available. Two subpopulations of this cohort were of primary interest in evaluating compliance with the medical surveillance provisions of the Cadmium Standard. These were a group of 16 workers medically removed from cadmium exposure due to elevations in some biological parameter, and a group of platemakers. Platemaking had presented a particularly high exposure opportunity and had recently undergone engineering interventions to minimize exposure. The effect on three biological monitoring parameters of medical removal protection in the first group and engineering controls in platemakers is reported. Results reveal that both medical removal from cadmium exposures and exposure abatement through the use of engineering and work practice controls generally result in declines in biological monitoring parameters of exposed workers. Implications for the success of interventions are discussed.

Cadmium resistance of endophytic bacteria and rizosféricas bacteria isolated from Oriza sativa in Colombia

Directory of Open Access Journals (Sweden)

Nataly Ayubb T

2017-12-01

Full Text Available The present study had as objective to evaluate in vitro the resistance of endophytic bacteria and rizospheric bacteria to different concentrations of Cadmium.This bacteria were isolated fron different tissues of commercial rice varieties and from bacteria isolated from the rhizosphere in rice plantations of the Nechí (Antioquía and Achí (Bolivar.  Plant growth promotion was evaluated in vitro by nitrogen fixation, phosphate solubilization and siderophores production of endophytic bacteria. Of each tissue isolated from rice plants was carried out isolation in culture medium for endophytic bacteria, and the soil samples were serially diluted in peptone water. Each sample was determined the population density by counting in CFU / g of tissue and morphotypes were separated by shape, color, size and appearance in culture media. Significant differences were observed for density population of bacteria with respect to tissue, with higher values in root (4x1011 g/root, followed of the stem (3x1010g/etem, leaf (5x109 g/ leaf, flag leaf (3x109 g/ flag leaf and with less density in panicle (4x108 g/panicle. The results of the identification with kit API were confirmed the presence of endophytic bacteria Burkholderia cepaceae and rizospheric bacteria Pseudomona fluorescens With the ability to tolerate different concentrations of Cd, fix nitrogen, solubilize phosphates and produce siderophores.

Environmental exposure to cadmium and renal function of elderly women living in cadmium-polluted areas of West-Germany

Energy Technology Data Exchange (ETDEWEB)

Ewers, U.; Brockhaus, A.; Dolgner, R.; Freier, I.; Jermann, E.; Hahn, R.; Schlipkoeter, H.W.; Bernard, A.

1985-12-01

An epidemiological study was carried out to assess whether or not environmental pollution by cadmium as found in cadmium-polluted areas of the Federal Republic auf Germany is associated with an increased prevalence of biological signs of kidney dysfunction in population groups non-occupationally exposed to heavy metals. The study was run in two industrial areas known to be highly polluted by cadmium and other toxic heavy metals, viz. Stolberg and Duisburg. Duesseldorf was selected as a reference area. As a study population we selected 65- and 66-year-old women who had spent the major part of their lives in one of these areas. The average levels of cadmium in blood and urine showed significant differences in exposure to cadmium in the order Stolberg > Duisburg > Duesseldorf. Serum creatinine levels were, on average, significantly higher in the Stolberg group than in the Duisburg and Duesseldorf groups. With respect to other biological findings (total proteinuria, tubular proteinuria, albuminuria, aminoaciduria, phosphaturia, serum complement) no significant differences between the study populations were noted. It cannot be excluded, however, that in the Stolberg group there is a synergism of ageing and cadmium with respect to the age related decline of the glomerular filtration rate.

Effect of pregnancy on cadmium-treated rats

Energy Technology Data Exchange (ETDEWEB)

Takizama, Y. (Akita Univ. School of Medicine, Japan); Nakamura, I.; Kurayama, R.; Hirasawa, F.; Kawai, K.

1982-01-01

It is well known that itai-itai disease with the osteopathy is broken out among multiparas, 40 years of age and up Japanese residents. In this paper we described an experimental study of effect of pregnancy on cadmium treated rats. Female mature rats were administered drinking water containing 50 and 200 ppm cadmium as CdCl/sub 2/. During 180 days of the experiment, three times of pregnancy were succesful, though slight depression of body weight gain was noticed in the 200 ppm group. The cadmium was accumulated in the kidneys, liver and bone proportionally to the amount of cadmium administered. No significant change was recognized in serum calcium, phosphorus and alkaline phosphatase levels after 180 days. Though cadmium 200 ppm treated rats showed slight histological lesions in the proximal convoluted tubules of the kidney, there appeared to be no osteomalacia including excess formation of osteoid tissue.

Specific features of the photoconductivity of semi-insulating cadmium telluride

Energy Technology Data Exchange (ETDEWEB)

Golubyatnikov, V. A.; Grigor’ev, F. I.; Lysenko, A. P., E-mail: aplysenko@hse.ru; Strogankova, N. I.; Shadov, M. B. [National Research University Higher School of Economics, Moscow Institute of Electronics and Mathematics (Russian Federation); Belov, A. G. [OAO GIREDMET State Research and Design Institute of the Rare-Metal Industry (Russian Federation)

2014-12-15

The effect of local illumination providing a high level of free-carrier injection on the conductivity of a sample of semi-insulating cadmium telluride and on the properties of ohmic contacts to the sample is studied. It is found that, irrespective of the illumination region, the contact resistance of ohmic contacts decreases and the concentration of majority carriers in the sample grows in proportion to the illumination intensity. It is shown that inherent heterogeneities in crystals of semi-insulating semiconductors can be studied by scanning with a light probe.

Proton MRS detects Metabolic Changes in Hormone Sensitive and Resistant Human Prostate Cancer Model CWR22 and CWR22r

Science.gov (United States)

Le, H. Carl; Lupu, Mihaela; Kotedia, Khushali; Rosen, Neal; Solit, David; Koutcher, Jason A.

2010-01-01

17-Allylamino, 17-Demethoxygeldanamycin (17-AAG), an effective inhibitor of the heat shock protein hsp90, preferentially inhibiting tumor hsp90 compared to hsp90 from normal cells (1), has shown promising results against several cancers, including hormone resistant prostate cancer. Levels of several oncogenic proteins critical to tumor growth and progression, such as AR (androgen receptor) and HER2/neu, were reduced 4 hours post 17-AAG treatment. Post treatment metabolic changes have also been observed in several tumor cell lines. In this study total choline (t-cho) distributions in hormone sensitive CWR22 and hormone resistant CWR22r prostate cancer xenograft tumors in mice were measured before, 4 hours and 48 hours after a single bolus 17-AAG treatment at 100 mg/kg using proton MRS. Our results show that tumor t-cho levels declined 4 hours after the treatment for CWR22 (P = 0.001) and 48 hours post treatment for CWR22r (P=0.003). Metabolic changes, in particular of t-cho intensity detected by 1H MRSI, are consistent with the observed immunohistochemistry changes, tumor growth inhibition for CWR22r (P=0.01 at 14 days post treatment) and a constant PSA level versus increasing PSA for control CWR22 (P=0.01). Metabolic changes in t-cho by proton MRSI can be used as an early biomarker of response for advanced stage prostate cancer in targeted therapy such as 17-AAG. PMID:19780165

Accumulation of cadmium in livers and kidneys in Greenlanders

International Nuclear Information System (INIS)

Johansen, Poul; Mulvad, Gert; Pedersen, Henning Sloth; Hansen, Jens C.; Riget, Frank

2006-01-01

In the Arctic, the traditional diet exposes its people to a very high intake of cadmium because it is highly concentrated in the liver and kidneys of commonly eaten marine mammals. In one study in Greenland, the cadmium intake was estimated to 182 μg/day/person in the fall and 346 in the spring. To determine whether the cadmium is accumulated in humans, we analyzed autopsy samples of liver and kidneys from 95 ethnic Greenlanders (aged 19-89) who died from a wide range of causes. The cadmium concentration in liver (overall mean 1.97 μg/g wet wt) appeared to be unrelated to any particular age group, whereas the concentrations in the kidneys peaked in Greenlanders between 40 and 50 years of age (peak concentration 22.3 μg/g wet wt). Despite the high cadmium levels in the typical Greenlander diet, we found that the cadmium concentrations in livers and kidneys were comparable to those reported from Denmark, Sweden, Australia and Great Britain. Furthermore, even though the mean cadmium intake from the diet was estimated to be 13-25 times higher in Greenlanders than in Danes, we found similar cadmium levels in the kidneys of both. Seal livers and kidneys are the main source of cadmium in the diet of Greenlanders, but these tissues are not eaten in Denmark. Thus, our results suggest that the accumulation of cadmium from Greenlander's marine diet is very low

Accumulation of cadmium in livers and kidneys in Greenlanders

Energy Technology Data Exchange (ETDEWEB)

Johansen, Poul [National Environmental Research Institute, Frederiksborgvej 399, DK-4000 Roskilde (Denmark)]. E-mail: poj@dmu.dk; Mulvad, Gert [Primary Health Care Center, DK-3900 Nuuk, Greenland (Denmark); Centre for Arctic Environmental Medicine, University of Aarhus, Universitetsparken, DK-8000 Aarhus C (Denmark); Pedersen, Henning Sloth [Primary Health Care Center, DK-3900 Nuuk, Greenland (Denmark); Centre for Arctic Environmental Medicine, University of Aarhus, Universitetsparken, DK-8000 Aarhus C (Denmark); Hansen, Jens C. [Centre for Arctic Environmental Medicine, University of Aarhus, Universitetsparken, DK-8000 Aarhus C (Denmark); Riget, Frank [National Environmental Research Institute, Frederiksborgvej 399, DK-4000 Roskilde (Denmark)

2006-12-15

In the Arctic, the traditional diet exposes its people to a very high intake of cadmium because it is highly concentrated in the liver and kidneys of commonly eaten marine mammals. In one study in Greenland, the cadmium intake was estimated to 182 {mu}g/day/person in the fall and 346 in the spring. To determine whether the cadmium is accumulated in humans, we analyzed autopsy samples of liver and kidneys from 95 ethnic Greenlanders (aged 19-89) who died from a wide range of causes. The cadmium concentration in liver (overall mean 1.97 {mu}g/g wet wt) appeared to be unrelated to any particular age group, whereas the concentrations in the kidneys peaked in Greenlanders between 40 and 50 years of age (peak concentration 22.3 {mu}g/g wet wt). Despite the high cadmium levels in the typical Greenlander diet, we found that the cadmium concentrations in livers and kidneys were comparable to those reported from Denmark, Sweden, Australia and Great Britain. Furthermore, even though the mean cadmium intake from the diet was estimated to be 13-25 times higher in Greenlanders than in Danes, we found similar cadmium levels in the kidneys of both. Seal livers and kidneys are the main source of cadmium in the diet of Greenlanders, but these tissues are not eaten in Denmark. Thus, our results suggest that the accumulation of cadmium from Greenlander's marine diet is very low.

Combinatorial treatment with lithium chloride enhances recombinant antibody production in transiently transfected CHO and HEK293E cells

DEFF Research Database (Denmark)

Kim, Che Lin; Kwang Ha, Tae; Min Lee, Gyun

2016-01-01

Lithium chloride (LiCl), which induces cell cycle arrest at G2/M phase, is known as a specific production rate (qp)-enhancing additive in recombinant Chinese hamster ovary (CHO) cell culture. To determine the potential of LiCl as a chemical additive that enhances transient gene expression (TGE), Li......Cl was added to the CHO-NK and human embryonic kidney 293E (HEK293E) cell cultures before and/or after transfection with polyethylenimine as a transfection reagent. The effect of this addition on transfection efficiency (pre-treatment) and qp enhancement during TGE (post-treatment) was examined. For the TGE...... of monoclonal antibody (mAb) in CHO-NK cells, pretreatment alone with 10 mM LiCl and post-treatment alone with 5 mM LiCl resulted in 1.2- and 3.4-fold increase of maximum mAb concentration (MMC), respectively, compared with the TGE without LiCl treatment. Furthermore, combinatorial treatment with LiCl (10 m...

Randomized Controlled Trial of Hospital-Based Hygiene and Water Treatment Intervention (CHoBI7) to Reduce Cholera.

Science.gov (United States)

George, Christine Marie; Monira, Shirajum; Sack, David A; Rashid, Mahamud-ur; Saif-Ur-Rahman, K M; Mahmud, Toslim; Rahman, Zillur; Mustafiz, Munshi; Bhuyian, Sazzadul Islam; Winch, Peter J; Leontsini, Elli; Perin, Jamie; Begum, Farzana; Zohura, Fatema; Biswas, Shwapon; Parvin, Tahmina; Zhang, Xiaotong; Jung, Danielle; Sack, R Bradley; Alam, Munirul

2016-02-01

The risk for cholera infection is >100 times higher for household contacts of cholera patients during the week after the index patient seeks hospital care than it is for the general population. To initiate a standard of care for this high-risk population, we developed Cholera-Hospital-Based-Intervention-for-7-Days (CHoBI7), which promotes hand washing with soap and treatment of water. To test CHoBI7, we conducted a randomized controlled trial among 219 intervention household contacts of 82 cholera patients and 220 control contacts of 83 cholera patients in Dhaka, Bangladesh, during 2013-2014. Intervention contacts had significantly fewer symptomatic Vibrio cholerae infections than did control contacts and 47% fewer overall V. cholerae infections. Intervention households had no stored drinking water with V. cholerae and 14 times higher odds of hand washing with soap at key events during structured observation on surveillance days 5, 6, or 7. CHoBI7 presents a promising approach for controlling cholera among highly susceptible household contacts of cholera patients.

Coprecipitation of cadmium with calcite

International Nuclear Information System (INIS)

Fujino, Osamu; Kumagai, Tetsu; Shigematsu, Tsunenobu; Matsui, Masakazu

1976-01-01

The distribution of cadmium between precipitates of calcite and saturated aqueous solution was measured at 25 0 C to understand the distribution of cadmium in the bivalves. Calcite was precipitated from calcium bicarbonate solution by the gradual release of carbon dioxide. The cadmium ions were coprecipitated in calcite, obeying the logarithmic distribution law. The apparent distribution coefficient was decreased as α, α'-dipyridyl increased, but the true distribution coefficient was found to be an almost constant value, 560. This value is fairly close to the ratio of solubility product constants K sub(calcite)/K sub(CdCO 3 ), 890. This suggests that the deviation of the present solid solution from ideality is not very large. (auth.)

Adhesion and migration of CHO cells on micropatterned single layer graphene

Science.gov (United States)

Keshavan, S.; Oropesa-Nuñez, R.; Diaspro, A.; Canale, C.; Dante, S.

2017-06-01

Cell patterning technology on single layer graphene (SLG) is a fairly new field that can find applications in tissue engineering and biomaterial/biosensors development. Recently, we have developed a simple and effective approach for the fabrication of patterned SLG substrates by laser micromachining, and we have successfully applied it for the obtainment of geometrically ordered neural networks. Here, we exploit the same approach to investigate the generalization of the cell response to the surface cues of the fabricated substrates and, contextually, to quantify cell adhesion on the different areas of the patterns. To attain this goal, we tested Chinese hamster ovary (CHO) cells on PDL-coated micropatterned SLG substrates and quantified the adhesion by using single cell force spectroscopy (SCFS). Our results indicate higher cell adhesion on PDL-SLG, and, consequently, an initial CHO cell accumulation on the graphene areas, confirming the neuronal behaviour observed previously; interestingly, at later time point in culture, cell migration was observed towards the adjacent SLG ablated regions, which resulted more favourable for cell proliferation. Therefore, our findings indicate that the mechanism of interaction with the surface cues offered by the micropatterned substrates is strictly cell-type dependent.

Microparticle-mediated transfer of the viral receptors CAR and CD46, and the CFTR channel in a CHO cell model confers new functions to target cells.

Directory of Open Access Journals (Sweden)

Gaëlle Gonzalez

Full Text Available Cell microparticles (MPs released in the extracellular milieu can embark plasma membrane and intracellular components which are specific of their cellular origin, and transfer them to target cells. The MP-mediated, cell-to-cell transfer of three human membrane glycoproteins of different degrees of complexity was investigated in the present study, using a CHO cell model system. We first tested the delivery of CAR and CD46, two monospanins which act as adenovirus receptors, to target CHO cells. CHO cells lack CAR and CD46, high affinity receptors for human adenovirus serotype 5 (HAdV5, and serotype 35 (HAdV35, respectively. We found that MPs derived from CHO cells (MP-donor cells constitutively expressing CAR (MP-CAR or CD46 (MP-CD46 were able to transfer CAR and CD46 to target CHO cells, and conferred selective permissiveness to HAdV5 and HAdV35. In addition, target CHO cells incubated with MP-CD46 acquired the CD46-associated function in complement regulation. We also explored the MP-mediated delivery of a dodecaspanin membrane glycoprotein, the CFTR to target CHO cells. CFTR functions as a chloride channel in human cells and is implicated in the genetic disease cystic fibrosis. Target CHO cells incubated with MPs produced by CHO cells constitutively expressing GFP-tagged CFTR (MP-GFP-CFTR were found to gain a new cellular function, the chloride channel activity associated to CFTR. Time-course analysis of the appearance of GFP-CFTR in target cells suggested that MPs could achieve the delivery of CFTR to target cells via two mechanisms: the transfer of mature, membrane-inserted CFTR glycoprotein, and the transfer of CFTR-encoding mRNA. These results confirmed that cell-derived MPs represent a new class of promising therapeutic vehicles for the delivery of bioactive macromolecules, proteins or mRNAs, the latter exerting the desired therapeutic effect in target cells via de novo synthesis of their encoded proteins.

Photolysis of CH₃CHO at 248 nm: evidence of triple fragmentation from primary quantum yield of CH₃ and HCO radicals and H atoms.

Science.gov (United States)

Morajkar, Pranay; Bossolasco, Adriana; Schoemaecker, Coralie; Fittschen, Christa

2014-06-07

Radical quantum yields have been measured following the 248 nm photolysis of acetaldehyde, CH3CHO. HCO radical and H atom yields have been quantified by time resolved continuous wave Cavity Ring Down Spectroscopy in the near infrared following their conversion to HO2 radicals by reaction with O2. The CH3 radical yield has been determined using the same technique following their conversion into CH3O2. Absolute yields have been deduced for HCO radicals and H atoms through fitting of time resolved HO2 profiles, obtained under various O2 concentrations, to a complex model, while the CH3 yield has been determined relative to the CH3 yield from 248 nm photolysis of CH3I. Time resolved HO2 profiles under very low O2 concentrations suggest that another unknown HO2 forming reaction path exists in this reaction system besides the conversion of HCO radicals and H atoms by reaction with O2. HO2 profiles can be well reproduced under a large range of experimental conditions with the following quantum yields: CH3CHO + hν(248nm) → CH3CHO*, CH3CHO* → CH3 + HCO ϕ(1a) = 0.125 ± 0.03, CH3CHO* → CH3 + H + CO ϕ(1e) = 0.205 ± 0.04, CH3CHO*[Formula: see text]CH3CO + HO2 ϕ(1f) = 0.07 ± 0.01. The CH3O2 quantum yield has been determined in separate experiments as ϕ(CH₃) = 0.33 ± 0.03 and is in excellent agreement with the CH3 yields derived from the HO2 measurements considering that the triple fragmentation (R1e) is an important reaction path in the 248 nm photolysis of CH3CHO. From arithmetic considerations taking into account the HO2 and CH3 measurements we deduce a remaining quantum yield for the molecular pathway: CH3CHO* → CH4 + CO ϕ(1b) = 0.6. All experiments can be consistently explained with absence of the formerly considered pathway: CH3CHO* → CH3CO + H ϕ(1c) = 0.

Chlorination leaching of cadmium

International Nuclear Information System (INIS)

Lach, E.; Pajak, I.; Bojanowska, A.

1978-01-01

The results of the investigations on chlorination leaching of cadmium from dust coming from dry dust collector of sinter belt, that is leaching with water saturated with gaseous chlorine and leaching with solutions of ammonium chloride and sodium chloride were given. The optimum conditions for these processes were established. It was found, that the method of leaching in the presence of gaseous chlorine is more effective, as it allows to report into the solution over 90% cadmium contained in dust. Owing to technical difficulties, environmental protection and safety conditions more advantageous seems to be the use as leaching agent of the ammonium chloride solutions. When applying 20% NH 4 Cl and temperature of 60 0 C, the time of 2 hours and the ratio of solid to liquid of 1:5, 70% cadmium contained in the dust can be reported into the solution. (auth.)

Synthesis of cadmium chalcogenide nanotubes at room temperature

KAUST Repository

Pan, Jun; Qian, Yitai

2012-01-01

Cadmium chalcogenide (CdE, E=S, Se, Te) polycrystalline nanotubes have been synthesized from precursor of CdS/cadmium thiolate complex at room temperature. The precursor was hydrothermally synthesized at 180 °C using thioglycolic acid (TGA) and cadmium acetate as starting materials. The transformation from the rod-like precursor of CdS/cadmium thiolate complex to CdS, CdSe and CdTe nanotubes were performed under constant stirring at room temperature in aqueous solution containing S 2-, Se 2- and Te 2-, respectively. The nanotube diameter can be controlled from 150 to 400 nm related to the dimension of templates. The XRD patterns show the cadmium chalcogenide nanotubes all corresponding to face-centered cubic structure. © 2012 Elsevier B.V. All rights reserved.

Synthesis of cadmium chalcogenide nanotubes at room temperature

KAUST Repository

Pan, Jun

2012-10-01

Cadmium chalcogenide (CdE, E=S, Se, Te) polycrystalline nanotubes have been synthesized from precursor of CdS/cadmium thiolate complex at room temperature. The precursor was hydrothermally synthesized at 180 °C using thioglycolic acid (TGA) and cadmium acetate as starting materials. The transformation from the rod-like precursor of CdS/cadmium thiolate complex to CdS, CdSe and CdTe nanotubes were performed under constant stirring at room temperature in aqueous solution containing S 2-, Se 2- and Te 2-, respectively. The nanotube diameter can be controlled from 150 to 400 nm related to the dimension of templates. The XRD patterns show the cadmium chalcogenide nanotubes all corresponding to face-centered cubic structure. © 2012 Elsevier B.V. All rights reserved.

Photolysis of CH3CHO at 248 nm: Evidence of triple fragmentation from primary quantum yield of CH3 and HCO radicals and H atoms

Science.gov (United States)

Morajkar, Pranay; Bossolasco, Adriana; Schoemaecker, Coralie; Fittschen, Christa

2014-06-01

Radical quantum yields have been measured following the 248 nm photolysis of acetaldehyde, CH3CHO. HCO radical and H atom yields have been quantified by time resolved continuous wave Cavity Ring Down Spectroscopy in the near infrared following their conversion to HO2 radicals by reaction with O2. The CH3 radical yield has been determined using the same technique following their conversion into CH3O2. Absolute yields have been deduced for HCO radicals and H atoms through fitting of time resolved HO2 profiles, obtained under various O2 concentrations, to a complex model, while the CH3 yield has been determined relative to the CH3 yield from 248 nm photolysis of CH3I. Time resolved HO2 profiles under very low O2 concentrations suggest that another unknown HO2 forming reaction path exists in this reaction system besides the conversion of HCO radicals and H atoms by reaction with O2. HO2 profiles can be well reproduced under a large range of experimental conditions with the following quantum yields: CH3CHO + hν248nm → CH3CHO*, CH3CHO* → CH3 + HCO ϕ1a = 0.125 ± 0.03, CH3CHO* → CH3 + H + CO ϕ1e = 0.205 ± 0.04, CH3CHO*{to 2pc{rArrfill}}limits^{o2}CH3CO + HO2 ϕ1f = 0.07 ± 0.01. The CH3O2 quantum yield has been determined in separate experiments as φ_{CH3} = 0.33 ± 0.03 and is in excellent agreement with the CH3 yields derived from the HO2 measurements considering that the triple fragmentation (R1e) is an important reaction path in the 248 nm photolysis of CH3CHO. From arithmetic considerations taking into account the HO2 and CH3 measurements we deduce a remaining quantum yield for the molecular pathway: CH3CHO* → CH4 + CO ϕ1b = 0.6. All experiments can be consistently explained with absence of the formerly considered pathway: CH3CHO* → CH3CO + H ϕ1c = 0.

Cadmium inhibits neurogenesis in zebrafish embryonic brain development

Energy Technology Data Exchange (ETDEWEB)

Chow, Elly Suk Hen [Division of Biology, California Institute of Technology, 1200 California Boulevard, Pasadena, CA 91125 (United States); Hui, Michelle Nga Yu; Lin Chunchi [Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong (China); Cheng Shukhan [Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong (China)], E-mail: bhcheng@cityu.edu.hk

2008-05-01

Cadmium is a non-essential heavy metal found abundantly in the environment. Children of women exposed to cadmium during pregnancy display lower motor and perceptual abilities. High cadmium body burden in children is also related to impaired intelligence and lowered school achievement. However, little is known about the molecular and cellular basis of developmental neurotoxicity in the sensitive early life stages of animals. In this study, we explore neurological deficits caused by cadmium during early embryonic stages in zebrafish by examining regionalization of the neural tube, pattern formation and cell fate determination, commitment of proneural genes and induction of neurogenesis. We show that cadmium-treated embryos developed a smaller head with unclear boundaries between the brain subdivisions, particularly in the mid-hindbrain region. Embryos display normal anterior to posterior regionalization; however, the commitment of neural progenitor cells was affected by cadmium. We observe prominent reductions in the expression of several proneuronal genes including ngn1 in cell clusters, zash1a in the developing optic tectum, and zash1b in the telencephalon and tectum. Cadmium-treated embryos also have fewer differentiated neurons and glia in the facial sensory ganglia as indicated by decreased zn-12 expression. Also, a lower transcription level of neurogenic genes, ngn1 and neuroD, is observed in neurons. Our data suggest that cadmium-induced neurotoxicity can be caused by impaired neurogenesis, resulting in markedly reduced neuronal differentiation and axonogenesis.

Cadmium inhibits neurogenesis in zebrafish embryonic brain development

International Nuclear Information System (INIS)

Chow, Elly Suk Hen; Hui, Michelle Nga Yu; Lin Chunchi; Cheng Shukhan

2008-01-01

Cadmium is a non-essential heavy metal found abundantly in the environment. Children of women exposed to cadmium during pregnancy display lower motor and perceptual abilities. High cadmium body burden in children is also related to impaired intelligence and lowered school achievement. However, little is known about the molecular and cellular basis of developmental neurotoxicity in the sensitive early life stages of animals. In this study, we explore neurological deficits caused by cadmium during early embryonic stages in zebrafish by examining regionalization of the neural tube, pattern formation and cell fate determination, commitment of proneural genes and induction of neurogenesis. We show that cadmium-treated embryos developed a smaller head with unclear boundaries between the brain subdivisions, particularly in the mid-hindbrain region. Embryos display normal anterior to posterior regionalization; however, the commitment of neural progenitor cells was affected by cadmium. We observe prominent reductions in the expression of several proneuronal genes including ngn1 in cell clusters, zash1a in the developing optic tectum, and zash1b in the telencephalon and tectum. Cadmium-treated embryos also have fewer differentiated neurons and glia in the facial sensory ganglia as indicated by decreased zn-12 expression. Also, a lower transcription level of neurogenic genes, ngn1 and neuroD, is observed in neurons. Our data suggest that cadmium-induced neurotoxicity can be caused by impaired neurogenesis, resulting in markedly reduced neuronal differentiation and axonogenesis

Diets high in resistant starch increase plasma levels of trimethylamine-N-oxide, a gut microbiome metabolite associated with CVD risk

Energy Technology Data Exchange (ETDEWEB)

Bergeron, Nathalie; Williams, Paul T.; Lamendella, Regina; Faghihnia, Nastaran; Grube, Alyssa; Li, Xinmin; Wang, Zeneng; Knight, Rob; Jansson, Janet K.; Hazen, Stanley L.; Krauss, Ronald M.

2016-12-20

Production of trimethylamine-N-oxide (TMAO), a biomarker of CVD risk, is dependent on intestinal microbiota, but little is known of dietary conditions promoting changes in gut microbial communities. Resistant starches (RS) alter the human microbiota. We sought to determine whether diets varying in RS and carbohydrate (CHO) content affect plasma TMAO levels. We also assessed postprandial glucose and insulin responses and plasma lipid changes to diets high and low in RS. In a cross-over trial, fifty-two men and women consumed a 2-week baseline diet (41 percentage of energy (%E) CHO, 40 % fat, 19 % protein), followed by 2-week high- and low-RS diets separated by 2-week washouts. RS diets were assigned at random within the context of higher (51–53 %E)v. lower CHO (39–40 %E) intake. Measurements were obtained in the fasting state and, for glucose and insulin, during a meal test matching the composition of the assigned diet. With lower CHO intake, plasma TMAO, carnitine, betaine andγ-butyrobetaine concentrations were higher after the high-v. low-RS diet (P<0·01 each). These metabolites were not differentially affected by highv. low RS when CHO intake was high. Although the high-RS meal reduced postprandial insulin and glucose responses when CHO intake was low (P<0·01 each), RS did not affect fasting lipids, lipoproteins, glucose or insulin irrespective of dietary CHO content. In conclusion, a lower-CHO diet high in RS was associated with higher plasma TMAO levels. These findings, together with the absence of change in fasting lipids, suggest that short-term high-RS diets do not improve markers of cardiometabolic health.

Modification of cadmium pigments for colouring of polyolefins

International Nuclear Information System (INIS)

Kalinskaya, T.V.; Livshits, I.M.

1976-01-01

Modification conditions are studied of cadmium pigments, obtained by different methods, aliphatic acids(C 5 , C 8 and C 17 ). It is found, that cadmium pigments can adsorb acids with the number of atoms of carbon not less than 8. Stearic acid adsorption on lemon cadmium pigment taken as an example has shown the efficiency of pigment modification influence on its dispersancy in non-polar medium. Modification of yellow cadmium pigments of stearic acid makes possible to obtain pigment output forms ensuring a good particle distribution during polyolefine colouring

Osteopontin splice variants are differential predictors of breast cancer treatment responses.

Science.gov (United States)

Zduniak, Krzysztof; Agrawal, Anil; Agrawal, Siddarth; Hossain, Md Monir; Ziolkowski, Piotr; Weber, Georg F

2016-07-11

Osteopontin is a marker for breast cancer progression, which in previous studies has also been associated with resistance to certain anti-cancer therapies. It is not known which splice variants may mediate treatment resistance. Here we analyze the association of osteopontin variant expression before treatment, differentiated according to immunohistochemistry with antibodies to exon 4 and to the osteopontin-c splice junction respectively, with the ensuing therapy responses in 119 Polish breast cancer patients who presented between 1995 and 2008. We found from Cox hazard models, logrank test and Wilcoxon test that osteopontin exon 4 was associated with a favorable response to tamoxifen, but a poor response to chemotherapy with CMF (cyclophosphamide, methotrexate, fluorouracil). Osteopontin-c is prognostic, but falls short of being a significant predictor for sensitivity to treatment. The addition of osteopontin splice variant immunohistochemistry to standard pathology work-ups has the potential to aid decision making in breast cancer treatment.

Osteopontin splice variants are differential predictors of breast cancer treatment responses

International Nuclear Information System (INIS)

Zduniak, Krzysztof; Agrawal, Anil; Agrawal, Siddarth; Hossain, Md Monir; Ziolkowski, Piotr; Weber, Georg F.

2016-01-01

Osteopontin is a marker for breast cancer progression, which in previous studies has also been associated with resistance to certain anti-cancer therapies. It is not known which splice variants may mediate treatment resistance. Here we analyze the association of osteopontin variant expression before treatment, differentiated according to immunohistochemistry with antibodies to exon 4 and to the osteopontin-c splice junction respectively, with the ensuing therapy responses in 119 Polish breast cancer patients who presented between 1995 and 2008. We found from Cox hazard models, logrank test and Wilcoxon test that osteopontin exon 4 was associated with a favorable response to tamoxifen, but a poor response to chemotherapy with CMF (cyclophosphamide, methotrexate, fluorouracil). Osteopontin-c is prognostic, but falls short of being a significant predictor for sensitivity to treatment. The addition of osteopontin splice variant immunohistochemistry to standard pathology work-ups has the potential to aid decision making in breast cancer treatment

In vitro and in vivo evaluation of Weissella cibaria and Lactobacillus plantarum for their protective effect against cadmium and lead toxicities.

Science.gov (United States)

Ojekunle, O; Banwo, K; Sanni, A I

2017-05-01

Thirty-two lactic acid bacteria (LAB) isolates were obtained from fermenting cassava mash and wara (African soft cheese) and screened for their resistance to cadmium and lead toxicities at 550-1050 mg l -1 and probiotic potentials. Four LAB strains that tolerated the heavy metals at 1050 mg l -1 were selected for antioxidative capacities, tolerance to acid, bile salts and simulated gastric and intestinal tract and safety status. The results revealed that Weissella cibaria WD2 and Lactobacillus plantarum CaD1 exhibited comparatively higher antioxidative capacities, survived in simulated gastric and intestinal transit, tolerated acid and bile salt and possessed safety status. The two strains were employed for the in vivo studies, which was monitored in male albino Wistar rats using skim milk as a carrier for the cultures over a period of 28 days. The rats given the cultures of W. cibaria WD2 and L. plantarum CaD1 in addition with the administration of heavy metals had improved renal and hepatic impairment, while damage was observed in rats fed with cadmium and lead only. Weissella cibaria WD2 and L. plantarum CaD1 demonstrated probiotic potentials and safety status. These strains can be used to effectively amend hepatic and renal histopathological alterations in rats caused by ingestion of cadmium and lead. This present study highlights the presence of lactic acid bacteria (LAB) from traditional fermented foods that were cadmium and lead resistant and possessed probiotic potentials. Weissella cibaria WD2 and Lactobacillus plantarum CaD1 selected for the in vivo studies ameliorated the build-up of cadmium and lead in the organs of the animals. This indicated that good cadmium and lead binding and probiotic lactic acid bacteria can be used to prevent exposure to these heavy metals. © 2017 The Society for Applied Microbiology.

Cadmium release from a reprocessing electrorefiner falling over

Energy Technology Data Exchange (ETDEWEB)

Solbrig, Charles W., E-mail: Charles.solbrig@inl.gov [Batelle Energy Alliance, Idaho National Laboratory, PO Box 2528, Idaho Falls, ID 83404 (United States); Pope, Chad L. [Batelle Energy Alliance, Idaho National Laboratory, PO Box 2528, Idaho Falls, ID 83404 (United States)

2013-02-15

Highlights: ► We model an accident in a nuclear fuel processing facility caused by an earthquake. ► The earthquake causes the argon cell to breach and the electrorefiner to tip over. ► Cadmium is spilled and a cathode falls on the cadmium and starts to burn. ► Cadmium can be transported to people in the building, the site, and the public. ► The results show negligible doses to all persons except in one low probability case. -- Abstract: The possible biological consequences of a release of cadmium due to a design basis earthquake in the Idaho Nuclear Laboratory's nuclear fuel reprocessing cell are evaluated. The facility is designed to withstand the design basis earthquake except for some non-seismically qualified feedthroughs. The earthquake is hypothesized to breach these feedthroughs (allowing air into the argon atmosphere processing cell) and cause the MK-IV electrorefiner (ER) in the cell to tip over or split and spill its contents of fission product laden salt and cadmium. In addition, the uranium dendrite product cathode is assumed to fall on the cadmium and burn. The heat from the burning cathode results in release of cadmium vapor into the cell atmosphere. Ingestion and inhalation of a sufficient concentration of cadmium for a critical time period can cause irreversible health effects or death. The release of the small quantity of fission products, analyzed elsewhere, results in negligible doses. Analysis reported here shows there is no danger to the general public by the cadmium release or to on-site workers except in one low probability case. This one case requires a fivefold failure where the safety exhaust system fails just after the 4% oxygen concentration combustion limit in the cell is reached. Failure of the SES allows oscillatory inflow and outflow (and hence cadmium outflow) from the cell due to gravity. The dose to a worker in the basement exceeds the mortality limit in this one event if the worker does not leave the basement.

Cadmium release from a reprocessing electrorefiner falling over

International Nuclear Information System (INIS)

Solbrig, Charles W.; Pope, Chad L.

2013-01-01

Highlights: ► We model an accident in a nuclear fuel processing facility caused by an earthquake. ► The earthquake causes the argon cell to breach and the electrorefiner to tip over. ► Cadmium is spilled and a cathode falls on the cadmium and starts to burn. ► Cadmium can be transported to people in the building, the site, and the public. ► The results show negligible doses to all persons except in one low probability case. -- Abstract: The possible biological consequences of a release of cadmium due to a design basis earthquake in the Idaho Nuclear Laboratory's nuclear fuel reprocessing cell are evaluated. The facility is designed to withstand the design basis earthquake except for some non-seismically qualified feedthroughs. The earthquake is hypothesized to breach these feedthroughs (allowing air into the argon atmosphere processing cell) and cause the MK-IV electrorefiner (ER) in the cell to tip over or split and spill its contents of fission product laden salt and cadmium. In addition, the uranium dendrite product cathode is assumed to fall on the cadmium and burn. The heat from the burning cathode results in release of cadmium vapor into the cell atmosphere. Ingestion and inhalation of a sufficient concentration of cadmium for a critical time period can cause irreversible health effects or death. The release of the small quantity of fission products, analyzed elsewhere, results in negligible doses. Analysis reported here shows there is no danger to the general public by the cadmium release or to on-site workers except in one low probability case. This one case requires a fivefold failure where the safety exhaust system fails just after the 4% oxygen concentration combustion limit in the cell is reached. Failure of the SES allows oscillatory inflow and outflow (and hence cadmium outflow) from the cell due to gravity. The dose to a worker in the basement exceeds the mortality limit in this one event if the worker does not leave the basement

Blood cadmium by race/hispanic origin: The role of smoking

Energy Technology Data Exchange (ETDEWEB)

Aoki, Yutaka, E-mail: yaoki@cdc.gov [Centers for Disease Control and Prevention, National Center for Health Statistics, Division of Health and Nutrition Examination Surveys, 3311 Toledo Rd, Hyattsville, MD 20782 (United States); Yee, Jennifer [Centers for Disease Control and Prevention, National Center for Health Statistics, Division of Health and Nutrition Examination Surveys, 3311 Toledo Rd, Hyattsville, MD 20782 (United States); Centers for Disease Control and Prevention, Center for Surveillance, Epidemiology, and Laboratory Services, Division of Scientific Education and Professional Development, Epidemiology Elective Program, MS E-92, 1600 Clifton Rd, NE, Atlanta, GA 30329 (United States); Georgetown University Medical Center, Department of Family Medicine, 4000 Reservoir Road, N.W., Washington D.C 20057 (United States); Mortensen, Mary E. [Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, MS F-20, 4770 Buford Highway, Atlanta, GA 30341 (United States)

2017-05-15

Background: There have been increasing concerns over health effects of low level exposure to cadmium, especially those on bones and kidneys. Objective: To explore how age-adjusted geometric means of blood cadmium in adults varied by race/Hispanic origin, sex, and smoking status among U.S. adults and the extent to which the difference in blood cadmium by race/Hispanic origin and sex may be explained by intensity of smoking, a known major source of cadmium exposure. Methods: Our sample included 7,368 adults from National Health and Nutrition Examination Survey (NHANES) 2011–2014. With direct age adjustment, geometric means of blood cadmium and number of cigarettes smoked per day were estimated for subgroups defined by race/Hispanic origin, smoking status, and sex using interval regression, which allows mean estimation in the presence of left- and right-censoring. Results: Among never and former smoking men and women, blood cadmium tended to be higher for non-Hispanic Asian adults than adults of other race/Hispanic origin. Among current smokers, who generally had higher blood cadmium than never and former smokers, non-Hispanic white, black, and Asian adults had similarly elevated blood cadmium compared to Hispanic adults. A separate analysis revealed that non-Hispanic white adults tended to have the highest smoking intensity regardless of sex, than adults of the other race/Hispanic origin groups. Conclusions: The observed pattern provided evidence for smoking as a major source of cadmium exposure, yet factors other than smoking also appeared to contribute to higher blood cadmium of non-Hispanic Asian adults. - Highlights: • Among never and former smoking adults, Asians have the highest blood cadmium. • White adults tend to have the highest smoking intensity, but not blood cadmium. • Women overall have higher levels of blood cadmium than men regardless of smoking. • Non-smoking sources of exposure likely contribute to Asians’ higher blood cadmium.

Blood cadmium by race/hispanic origin: The role of smoking

International Nuclear Information System (INIS)

Aoki, Yutaka; Yee, Jennifer; Mortensen, Mary E.

2017-01-01

Background: There have been increasing concerns over health effects of low level exposure to cadmium, especially those on bones and kidneys. Objective: To explore how age-adjusted geometric means of blood cadmium in adults varied by race/Hispanic origin, sex, and smoking status among U.S. adults and the extent to which the difference in blood cadmium by race/Hispanic origin and sex may be explained by intensity of smoking, a known major source of cadmium exposure. Methods: Our sample included 7,368 adults from National Health and Nutrition Examination Survey (NHANES) 2011–2014. With direct age adjustment, geometric means of blood cadmium and number of cigarettes smoked per day were estimated for subgroups defined by race/Hispanic origin, smoking status, and sex using interval regression, which allows mean estimation in the presence of left- and right-censoring. Results: Among never and former smoking men and women, blood cadmium tended to be higher for non-Hispanic Asian adults than adults of other race/Hispanic origin. Among current smokers, who generally had higher blood cadmium than never and former smokers, non-Hispanic white, black, and Asian adults had similarly elevated blood cadmium compared to Hispanic adults. A separate analysis revealed that non-Hispanic white adults tended to have the highest smoking intensity regardless of sex, than adults of the other race/Hispanic origin groups. Conclusions: The observed pattern provided evidence for smoking as a major source of cadmium exposure, yet factors other than smoking also appeared to contribute to higher blood cadmium of non-Hispanic Asian adults. - Highlights: • Among never and former smoking adults, Asians have the highest blood cadmium. • White adults tend to have the highest smoking intensity, but not blood cadmium. • Women overall have higher levels of blood cadmium than men regardless of smoking. • Non-smoking sources of exposure likely contribute to Asians’ higher blood cadmium.

Oral cadmium chloride intoxication in mice

DEFF Research Database (Denmark)

Andersen, O; Nielsen, J B; Svendsen, P

1988-01-01

Diethyldithiocarbamate (DDC) is known to alleviate acute toxicity due to injection of cadmium salts. However, when cadmium chloride was administered by the oral route, DDC enhanced rather than alleviated the acute toxicity; both oral and intraperitoneal (i.p.) administration of DDC had this effect...

Lead and cadmium content of spices

Energy Technology Data Exchange (ETDEWEB)

Bielig, H J; Dreyer, H; Askar, A

1977-02-02

The lead and cadmium content of various spices was determined by flameless atomic absorption (AAS). With the exception of one sample, the lead content was lower than 5 ppm, averaging a value of 2,2 ppm Pb. Thus, the maximum permissible level of 5 ppm Pb as recommended by different DIN standards, is not exceeded. The cadmium content was - except for one sample - lower than 0,5 ppm averaging a value of 0,23 ppm Cd. It can be assumed, that by spicing our dishes, the ingestion of lead and cadmium stays at a low level.

Cadmium decontamination using in-house resin

International Nuclear Information System (INIS)

Pal, Sangita; Thalor, K.L; Prabhakar, S.; Srivastava, V.K.; Goswami, J.L.; Tewari, P.K.; Dhanpal, Pranav; Goswami, J.L.

2010-01-01

A selective and strong in-house chelator has been studied w.r.t. basic parameters like concentration, time, and elution. De-contamination of cadmium, mercury, chromium, lead etc by using high uptake values fro cadmium ions proves its selectivity with high elution ratio ensures further decontamination of run-off water during natural calamities. In three step cascade use the concentration of original cadmium solution (500 ppm) decocted to safe disposable attribute. This polymeric ligand exchanger displayed outlet effluent concentration to 1 ppm and less than 200 ppb when treated for inlet feed concentration of 50 ppm and 500 ppm respectively. (author)

New process to discharge negative cadmium electrodes for Ni/Cd batteries

International Nuclear Information System (INIS)

Stiker, B.; Vignaud, R.

1984-01-01

The new process relates to the chemical oxidation (whether partial or total) of cadmium metal negative electrodes, as used in alkaline nickel-cadmium or silver-cadmium batteries. This process concerns all cadmium electrodes but more particularly the electrodeposited cadmium electrode developed by the company LES PILES WONDER and described in this publication

Genetic variants and traits related to insulin-like growth factor-I and insulin resistance and their interaction with lifestyles on postmenopausal colorectal cancer risk.

Directory of Open Access Journals (Sweden)

Su Yon Jung

Full Text Available Genetic variants and traits in metabolic signaling pathways may interact with lifestyle factors such as obesity, physical activity, and exogenous estrogen (E, influencing postmenopausal colorectal cancer (CRC risk, but these interrelated pathways are not fully understood. In this case-cohort study, we examined 33 single-nucleotide polymorphisms (SNPs in genes related to insulin-like growth factor-I (IGF-I/ insulin resistance (IR traits and signaling pathways, using data from 704 postmenopausal women in Women's Health Initiative Observation ancillary studies. Stratifying by the lifestyle modifiers, we assessed the effects of IGF-I/IR traits (fasting total and free IGF-I, IGF binding protein-3, insulin, glucose, and homeostatic model assessment-insulin resistance on CRC risk as a mediator or influencing factor. Six SNPs in the INS, IGF-I, and IGFBP3 genes were associated with CRC risk, and those associations differed between non-obese/active and obese/inactive women and between E nonusers and users. Roughly 30% of the cancer risk due to the SNP was mediated by IGF-I/IR traits. Likewise, carriers of 11 SNPs in the IRS1 and AKT1/2 genes (signaling pathway-related genetic variants had different associations with CRC risk between strata, and the proportion of the SNP-cancer association explained by traits varied from 30% to 50%. Our findings suggest that IGF-I/IR genetic variants interact with obesity, physical activity, and exogenous E, altering postmenopausal CRC risk, through IGF-I/IR traits, but also through different pathways. Unraveling gene-phenotype-lifestyle interactions will provide data on potential genetic targets in clinical trials for cancer prevention and intervention strategies to reduce CRC risk.

Calcium enhances cadmium tolerance and decreases cadmium ...

African Journals Online (AJOL)

Yomi

2012-04-26

Apr 26, 2012 ... concentrations alleviated the toxic effect of cadmium on the growth and water status of lettuce plants. The three lettuce varieties ... electroplating, in batteries, in electrical conductors, in the manufacture of alloys ..... Handbook on the Toxicology of Metals, Third edition, Salt Lake City, UT: Acad. Press. Österås ...

Synthesis and Characterization of Mercaptoacetic Acid Capped Cadmium Sulphide Quantum Dots.

Science.gov (United States)

Wageh, S; Maize, Mai; Donia, A M; Al-Ghamdi, Ahmed A; Umar, Ahmad

2015-12-01

This paper reports the facile synthesis and detailed characterization of mercaptoacetic acid capped cadmium sulphide (CdS) quantum dots using various cadmium precursors. The mercaptoacetic acid capped CdS quantum dots were prepared by facile and simple wet chemical method and characterized by several techniques such as energy dispersive spectroscopy (EDS), X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy, UV-vis. spectroscopy, photoluminescence spectroscopy, high-resolution transmission microscopy (HRTEM) and thremogravimetric analysis. The EDS studies revealed that the prepared quantum dots possess higher atomic percentage of sulfur compared to cadmium due to the coordination of thiolate to the quantum dots surfaces. The X-ray and absorption analyses exhibited that the size of quantum dots prepared by cadmium acetate is larger than the quantum dots prepared by cadmium chloride and cadmium nitrate. The increase in size can be attributed to the low stability constant of cadmium acetate in comparison with cadmium chloride and cadmium nitrate. The FTIR and thermogravimetric analysis showed that the nature of capping molecule on the surface of quantum dots are different depending on the cadmium precursors which affect the emission from CdS quantum dots. Photoemission spectroscopy revealed that the emission of quantum dots prepared by cadmium acetate has high intensity band edge emission along with low intensity trapping state emission. However the CdS quantum dots prepared by cadmium chloride and cadmium nitrate produced only trapping state emissions.

Endocrine-Therapy-Resistant ESR1 Variants Revealed by Genomic Characterization of Breast-Cancer-Derived Xenografts

Directory of Open Access Journals (Sweden)

Shunqiang Li

2013-09-01

Full Text Available To characterize patient-derived xenografts (PDXs for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation.

Cadmium uptake in oyster isognomon alatus under laboratory condition

International Nuclear Information System (INIS)

Katayon Saed; Ahmad Ismail; Missri Kusnan; Hishamuddin Omar

1999-01-01

The uptake of cadmium in Flat tree oyster Isognomon alatus was investigated under controlled laboratory conditions for two weeks. Oysters were exposed to 100 μg 1'-1 cadmium and the accumulation of cadmium in the tissues was measured for every two days. Soft tissues of oyster were digested in concentrated acid and cadmium concentrations were determined by using Atomic Absorption Spectrophotometer. The accumulation of cadmium in the soft tissues of oysters was increased during the first six days from 0.73 μg g- 1 to 10.77 μg g'-1, and remaining constant for four days at average level of 10.96 μg g'-1. The Cl concentrations was increased to 32.70 μg g'-1 until the end of experiment. There was no sign of cadmium accumulation approaching saturation for the period of exposure. (author)

Effect of cadmium on myocardial contractility and calcium fluxes

International Nuclear Information System (INIS)

Pilati, C.F.

1979-01-01

The effect of cadmium on myocardial mechanical performance and calcium fluxes was studied in kitten isometric papillary muscles and in isovolumic Langendorff-perfused rabbit hearts. Therefore, it is concluded that cadmium-induced decreases in contractility are not primarily the result of cadmium interference with ATP metabolic processes. Furthermore, these results imply that cadmium causes no structural alterations of the contractile proteins. These data suggest that cadmium may be competing with the calcium needed for excitation-contraction coupling. During experiments using radioisotopic calcium, a statistically significant cellular influx of calcium was observed following the onset of 100 μM Cd ++ perfusion of isolated, Langendorff-prepared rabbit hearts

Cadmium chronic administration to lactating ewes. Reproductive performance, cadmium tissue accumulation and placental transfer

Energy Technology Data Exchange (ETDEWEB)

Floris, B.; Bomboi, G.; Sechi, P.; Marongiu, M. L. [Sassari Univ., Sassari (Italy). Dipt. di Biologia Animale; Pirino, S. [Sassari Univ., Sassari (Italy). Ist. di Patologia Generale, Anatomia Patologica e Clinica Ostetrico-chirurgica Veterinaria

2000-12-01

20 lactating ewes were allotted to two groups: 10 subjects received orally 100 mg/day of CdCl{sub 2} for 108 consecutive days, and the remaining 10 acted as control. Reproductive performance in ewes and cadmium tissue accumulation, both in ewes and their lambs, were investigated. The results showed that in ewes: 1) the regular cadmium intestinal intake negatively influences all reproductive parameters; 2) cadmium is particularly accumulated in kidney and liver, bur also in mammary gland, although at distinctly lower level; 3) chronic administration does not increase cadmium placental transfer in lactating pregnant subjects. [Italian] 20 pecore in lattazione sono state suddivise in 2 gruppi: 10 soggetti ricevettero per os 100 mg/giorno di CdCl{sub 2} per 108 giorni consecutivi, e i restanti 10 funsero da controllo. Sono stati studiati i parametri riproduttivi delle pecore e l'accumulo di cadmio nei tessuti, sia delle pecore che dei loro agnelli. I risultati hanno mostrato che negli ovini: 1) il regolare assorbimento intestinale di cadmio influenza negativamente tutti i parametri riproduttivi; 2) il cadmio viene accumulato principalmente nei reni e nel fegato, ma anche dalla ghiandola mammaria, sebbene in misura nettamente inferiore; 3) la somministrazione cronica di cadmio nei soggetti gravidi non incrementa il suo passaggio transplacentare.

Cadmium Exposure is Associated with the Prevalence of Dyslipidemia

OpenAIRE

Zhou Zhou; Yong-hui Lu; Hui-feng Pi; Peng Gao; Min Li; Lei Zhang; Li-ping Pei; Xiang Mei; Lin Liu; Qi Zhao; Qi-Zhong Qin; Yu Chen; Yue-ming Jiang; Zhao-hui Zhang; Zheng-ping Yu

2016-01-01

Background: Cadmium is a widespread environmental and occupational pollutant that accumulates in human body with a biological half-life exceeding 10 years. Cadmium exposure has been demonstrated to increase rates of cardiovascular diseases. Whether occupational cadmium exposure is associated with the increase in the prevalence of dyslipidemia and hence contributes to the risk of cardiovascular diseases is still equivocal. To test the hypothesis that exposure to cadmium is related to the preva...

Stabilization of cadmium electrode properties when introducing surfactants

International Nuclear Information System (INIS)

Alekseeva, M.E.; Mansurov, F.Kh.; Nikol'skij, V.A.

1995-01-01

The results of tests of both separate cadmium electrodes and silver-cadmium accumulators, depending on introduction of surfactants (polyethylene oxide - PO - and its derivatives), have been considered. The influence of PO on the course of electrochemical reaction on cadmium is pronounced in facilitation of anodic process. In case of PO introduction in the amount of 1 % instead of sodium lignosulfonate (2 %) into accumulators with silver-cadmium electrodes, the electrode potential is stabilized, while the accumulator capacity increases. The time period of the accumulation maintenance in the charged state increases 2-3 fold (1-1,5 years). 5 refs.; 4 figs.; 2 tabs

Cadmium exposure and health risks: Recent findings

Energy Technology Data Exchange (ETDEWEB)

Elinder, C.G. [Huddinge Hospital (Sweden). Dept. of Renal Medicine; Jaerup, L. [Stockholm City Council (Sweden). Dept. of Environmental Health

1996-08-01

Environmental and/or occupational exposure to cadmium give rise to a tubular kidney dysfunction which may proceed to more generalized renal damage and bone disease if exposure has been high and prolonged. Recent scientific work shows that early renal effects develop at lower levels of exposure than previously anticipated. Previous risk assessments for cadmium were mainly based on studies on healthy male workers. The general population, however, also include particularly susceptible groups such as elderly and individuals with illnesses (e.g. diabetes) that may predispose to cadmium-induced health effects. A significant proportion of the general population displays early signs of toxicity already at urinary cadmium concentrations around 3 nmol mmol{sup -1} creatinine. In addition to early tubular effects, cadmium may exert direct or indirect effects on mineral metabolism and the mineralization of the skeleton at relatively low levels of exposure. This may have important health implications, as poor and easily fractured bone is a major problem among the elderly in all industrialized countries. 41 refs, 4 figs

An experimental study of the retention of zinc, zinc-cadmium mixture and zinc-65 in the presence of cadmium in Anguilla anguilla (L.)

International Nuclear Information System (INIS)

Pally, Monique; Foulquier, Luc

1976-07-01

Zinc uptake was studied in eels in fresh water, using stable zinc, a zinc-cadmium mixture, and zinc 65 in the presence of small amounts of cadmium. The zinc content in the eel began to increase after 45 days only, and reached approximately 85 ppm after 76 days in water initially containing 5ppm of zinc. At the conclusion of the experiment (76 days), the body organs could be classified in decreasing order in zinc content (in ppm): kidneys (152), skeleton (133), skin (129), muscles (89), head (80), gills (78), digestive tract (77), liver (63) spleen-heart-air bladder (32), and mucus (15). A comparison of experimental results obtained with the zinc-cadmium mixture and cadmium alone showed that zinc decreased the cadmium content of all organs except the gills. The presence of cadmium in water did not inhibit zinc uptake. As cadmium content in water increased, then zinc content in the digestive tract and the kidneys decreased and in all cases remained lower than when zinc alone was present. In the presence of cadmium the percentage of zinc in the kidneys was always lower than the value obtained for zinc alone, and that of the digestive tract did not increase. Contamination of eels treated with 18 and 50ppb of cadmium for 29 days, then contaminated by zinc-65 (5μCi/l) while maintaining the same low cadmium content, showed no significant difference in zinc 65 uptake in the two groups. The same applied to the body organs, and particularly the digestive tract and kidneys, where the highest activity levels were observed. By weight, muscles represented approximately 30% of the total contamination after 45 days [fr

Boron-doped cadmium oxide composite structures and their electrochemical measurements

Energy Technology Data Exchange (ETDEWEB)

Lokhande, B.J., E-mail: bjlokhande@yahoo.com [Lab of Smart Mtrls Supercapacitive and Energy Studies, School of Physical Sciences, Solapur University, Solapur 413255, Maharashtra (India); Ambare, R.C. [Lab of Smart Mtrls Supercapacitive and Energy Studies, School of Physical Sciences, Solapur University, Solapur 413255, Maharashtra (India); Mane, R.S. [School of Physical Sciences, Swami Ramanand Teerth Marathwada University, Nanded 431606 (India); Bharadwaj, S.R. [Chemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India)

2013-08-01

Graphical abstract: Conducting nano-fibrous 3% boron doped cadmium oxide thin films were prepared by SILAR and its super capacitive properties were studied. - Highlights: • Samples are of nanofibrous nature. • All samples shows pseudocapacitive behavior. • 3% B doped CdO shows good specific capacitance. • 3% B doped CdO shows maximum 74.93% efficiency at 14 mA/cm{sup 2}. • 3% B doped CdO shows 0.8 Ω internal resistance. - Abstract: Boron-doped and undoped cadmium oxide composite nanostructures in thin film form were prepared onto stainless steel substrates by a successive ionic layer adsorption and reaction method using aqueous solutions of cadmium nitrate, boric acid and 1% H{sub 2}O{sub 2}. As-deposited films were annealed at 623 K for 1 h. The X-ray diffraction study shows crystalline behavior for both doped and undoped films with a porous topography and nano-wires type architecture, as observed in SEM image. Wettability test confirms the hydrophilic surface with 58° contact angle value. Estimated band gap energy is around 1.9 eV. Electrochemical behavior of the deposited films is attempted in 1 M KOH electrolyte using cyclic voltammetry (CV), electrochemical impedance spectroscopy and galvanostatic charge–discharge tests. Maximum values of the specific capacitance, specific energy and specific power obtained for 3% B doped CdO film at 2 mV/s scan rate are 20.05 F/g, 1.22 Wh/kg and 3.25 kW/kg, respectively.

Polarographic studies on the nature of cadmium in scallop, oyster, and lobster

Energy Technology Data Exchange (ETDEWEB)

Chou, C L; Uthe, J F; Zook, E G

1978-04-01

Free and bound forms of cadmium were determined in raw shellfish by use of differential pulse polarography and atomic absorption spectrophotometry. Free cadmium is defined by its polarographic peak potential of -0.62 +- 0.02 V (saturated calomel electrode) in solvent washed ammonium sulfate extracts. Bound cadmium was determined by subtracting the free cadmium from the total cadmium present in the meat. Both scallop (various species) and American lobster (Homarus americanus) muscle tissues contain no free cadmium. Oyster (various species), on the other hand, had a considerable percentage (approximately 50%) of its total cadmium present as free cadmium, a phenomena as yet unexplained. The detection limit for free cadmium is approximately 0.05 ..mu..g/g raw tissue.

Investigation of the interactions of critical scale-up parameters (pH, pO2 and pCO2) on CHO batch performance and critical quality attributes.

Science.gov (United States)

Brunner, Matthias; Fricke, Jens; Kroll, Paul; Herwig, Christoph

2017-02-01

Understanding process parameter interactions and their effects on mammalian cell cultivations is an essential requirement for robust process scale-up. Furthermore, knowledge of the relationship between the process parameters and the product critical quality attributes (CQAs) is necessary to satisfy quality by design guidelines. So far, mainly the effect of single parameters on CQAs was investigated. Here, we present a comprehensive study to investigate the interactions of scale-up relevant parameters as pH, pO 2 and pCO 2 on CHO cell physiology, process performance and CQAs, which was based on design of experiments and extended product quality analytics. The study used a novel control strategy in which process parameters were decoupled from each other, and thus allowed their individual control at defined set points. Besides having identified the impact of single parameters on process performance and product quality, further significant interaction effects of process parameters on specific cell growth, specific productivity and amino acid metabolism could be derived using this method. Concerning single parameter effects, several monoclonal antibody (mAb) charge variants were affected by process pCO 2 and pH. N-glycosylation analysis showed positive correlations between mAb sialylation and high pH values as well as a relationship between high mannose variants and process pH. This study additionally revealed several interaction effects as process pH and pCO 2 interactions on mAb charge variants and N-glycosylation pattern. Hence, through our process control strategy and multivariate investigation, novel significant process parameter interactions and single effects were identified which have to be taken into account especially for process scale-up.

Study on thermal annealing of cadmium zinc telluride (CZT) crystals

International Nuclear Information System (INIS)

Yang, G.; Bolotnikov, A.E.; Fochuk, P.M.; Camarda, G.S.; Cui, Y.; Hossain, A.; Kim, K.; Horace, J.; McCall, B.; Gul, R.; Xu, L.; Kopach, O.V.; James, R.B.

2010-01-01

Cadmium Zinc Telluride (CZT) has attracted increasing interest with its promising potential as a room-temperature nuclear-radiation-detector material. However, different defects in CZT crystals, especially Te inclusions and dislocations, can degrade the performance of CZT detectors. Post-growth annealing is a good approach potentially to eliminate the deleterious influence of these defects. At Brookhaven National Laboratory (BNL), we built up different facilities for investigating post-growth annealing of CZT. Here, we report our latest experimental results. Cd-vapor annealing reduces the density of Te inclusions, while large temperature gradient promotes the migration of small-size Te inclusions. Simultaneously, the annealing lowers the density of dislocations. However, only-Cd-vapor annealing decreases the resistivity, possibly reflecting the introduction of extra Cd in the lattice. Subsequent Te-vapor annealing is needed to ensure the recovery of the resistivity after removing the Te inclusions.

Cadmium affects retinogenesis during zebrafish embryonic development

International Nuclear Information System (INIS)

Hen Chow, Elly Suk; Yu Hui, Michelle Nga; Cheng, Chi Wa; Cheng, Shuk Han

2009-01-01

Ocular malformations are commonly observed in embryos of aquatic species after exposure to toxicants. Using zebrafish embryos as the model organism, we showed that cadmium exposure from sphere stage (4 hpf) to end of segmentation stage (24 hpf) induced microphthalmia in cadmium-treated embryos. Embryos with eye defects were then assessed for visual abilities. Cadmium-exposed embryos were behaviorally blind, showing hyperpigmentation and loss of camouflage response to light. We investigated the cellular basis of the formation of the small eyes phenotype and the induction of blindness by studying retina development and retinotectal projections. Retinal progenitors were found in cadmium-treated embryos albeit in smaller numbers. The number of retinal ganglion cells (RGC), the first class of retinal cells to differentiate during retinogenesis, was reduced, while photoreceptor cells, the last batch of retinal neurons to differentiate, were absent. Cadmium also affected the propagation of neurons in neurogenic waves. The neurons remained in the ventronasal area and failed to spread across the retina. Drastically reduced RGC axons and disrupted optic stalk showed that the optic nerves did not extend from the retina beyond the chiasm into the tectum. Our data suggested that impairment in neuronal differentiation of the retina, disruption in RGC axon formation and absence of cone photoreceptors were the causes of microphthalmia and visual impairment in cadmium-treated embryos

Human health effects of exposure to cadmium

Energy Technology Data Exchange (ETDEWEB)

Hallenbeck, W.H.

1986-01-01

The health effects of human exposure to cadmium are discussed with emphases on intake, absorption, body burden, and excretion; osteomalacia in Japan; hypertension; and proteinuria, emphysema, osteomalacia, and cancer in workers. Elevated blood pressure has not been observed as a result of excessive exposures to cadmium in Japan or the workplace. Renal tubular dysfunction and consequent proteinuria is generally accepted as the main effect following long-term, low-level exposure to cadmium. Studies of workers show that proteinuria may develop after the first year of exposure or many years after the last exposure. Proteinuria and deterioration of renal function may continue even after cessation of exposure. The immediate health significance of low-level proteinuria is still under debate. However, there is evidence that long-term renal tubular dysfunction may lead to abnormalities of calcium metabolism and osteomalacia. The few autopsy and cross-sectional studies of workers do not permit conclusions to be drawn regarding the relationship between cadmium exposure and emphysema. Retrospective and historical-prospective studies are needed to settle this important question. No conclusive evidence has been published regarding cadmium-induced cancer in humans. However, there is sufficient evidence to regard cadmium as a suspect renal and prostate carcinogen. Because of equivocal results and the absence of dose-response relationships, the studies reviewed should be used with caution in making regulatory decisions and low-dose risk assessments. 62 references.

Human health effects of exposure to cadmium

Energy Technology Data Exchange (ETDEWEB)

Hallenbeck, W.H.

1984-02-15

The health effects of human exposure to cadmium are discussed with emphasis on intake, absorption, body burden, and excretion; osteomalacia in Japan; hypertension; and proteinuria, emphysema, osteomalacia, and cancer in workers. Elevated blood pressure has not been observed as a result of excessive exposures to cadmium in Japan or the workplace. Renal tubular dysfunction and consequent proteinuria is generally accepted as the main effect following long-term, low-level exposure to cadmium. Studies of workers show that proteinuria may develop after the first year of exposure or many years after the last exposure. Proteinuria and deterioration of renal function may continue even after cessation of exposure. The immediate health significance of low-level proteinuria is still under debate. However, there is evidence that long-term renal tubular dysfunction may lead to abnormalities of calcium metabolism and osteomalacia. The few autopsy and cross-sectional studies of workers do not permit conclusions to be drawn regarding the relationship between cadmium exposure and emphysema. Retrospective and historical-prospective studies are needed to settle this important question. No conclusive evidence has been published regarding cadmium-induced cancer in humans. However, there is sufficient evidence to regard cadmium as a suspect renal and prostate carcinogen. Because of equivocal results and the absence of dose-response relationships, the studies reviewed should be used with caution in making regulatory decisions and low-dose risk assessments.

[Physiological response and bioaccumulation of Panax notoginseng to cadmium under hydroponic].

Science.gov (United States)

Li, Zi-wei; Yang, Ye; Cui, Xiu-ming; Liao, Pei-ran; Ge, Jin; Wang, Cheng-xiao; Yang, Xiao-yan; Liu, Da-hui

2015-08-01

The physiological response and bioaccumulation of 2-year-old Panax notoginseng to cadmium stress was investigated under a hydroponic experiment with different cadmium concentrations (0, 2.5, 5, 10 μmol · L(-1)). Result showed that low concentration (2.5 μmol · L(-1)) of cadmium could stimulate the activities of SOD, POD, APX in P. notoginseng, while high concentration (10 μmol · L(-1)) treatment made activities of antioxidant enzyme descended obviously. But, no matter how high the concentration of cadmium was, the activities of CAT were inhibited. The Pn, Tr, Gs in P. notoginseng decreased gradually with the increase of cadmium concentration, however Ci showed a trend from rise to decline. The enrichment coefficients of different parts in P. notoginseng ranked in the order of hair root > root > rhizome > leaf > stem, and all enrichment coefficients decreased with the increase of concentration of cadmium treatments; while the cadmium content in different parts of P. notoginseng and the transport coefficients rose. To sum up, cadmium could affect antioxidant enzyme system and photosynthetic system of P. notoginseng; P. notoginseng had the ability of cadmium enrichment, so we should plant it in suitable place reduce for reducing the absorption of cadmium; and choose medicinal parts properly to lessen cadmium intake.

Cadmium exposure induces hematuria in Korean adults

Energy Technology Data Exchange (ETDEWEB)

Han, Seung Seok [Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Kim, Myounghee, E-mail: dkkim73@gmail.com [Department of Dental Hygiene, College of Health Science, Eulji University, Gyeonggi-do 461-713 (Korea, Republic of); Lee, Su Mi [Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Lee, Jung Pyo [Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul 156-707 (Korea, Republic of); Kim, Sejoong [Department of Internal Medicine, Seoul National University Bundang Hospital, Gyeonggi-do 463-707 (Korea, Republic of); Joo, Kwon Wook [Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Lim, Chun Soo [Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul 156-707 (Korea, Republic of); Kim, Yon Su; Kim, Dong Ki [Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of)

2013-07-15

Introduction: Toxic heavy metals have adverse effects on human health. However, the risk of hematuria caused by heavy metal exposure has not been evaluated. Methods: Data from 4701 Korean adults were obtained in the Korean National Health and Nutritional Examination Survey (2008–2010). Blood levels of the toxic heavy metals cadmium, lead, and mercury were measured. Hematuria was defined as a result of ≥+1 on a urine dipstick test. The odds ratios (ORs) for hematuria were measured according to the blood heavy metal levels after adjusting for multiple variables. Results: Individuals with blood cadmium levels in the 3rd and 4th quartiles had a greater OR for hematuria than those in the 1st quartile group: 3rd quartile, 1.35 (1.019–1.777; P=0.037); 4th quartile, 1.52 (1.140–2.017; P=0.004). When blood cadmium was considered as a log-transformed continuous variable, the correlation between blood cadmium and hematuria was significant: OR, 1.97 (1.224–3.160; P{sub trend}=0.005). In contrast, no significant correlations between hematuria and blood lead or mercury were found in the multivariate analyses. Discussion: The present study shows that high cadmium exposure is associated with a risk of hematuria. -- Highlights: • A high level of blood cadmium is associated with a high risk of hematuria. • This correlation is independent of several confounding factors. • Blood levels of lead and mercury are not associated with risk of hematuria. • This is the first study on the correlation between cadmium exposure and hematuria risk.

A study on complex formation of cadmium(II) ions, 8

International Nuclear Information System (INIS)

Matsui, Haruo; Hirabayashi, Yoshihiro

1984-01-01

In the potentiometric titration of the solution containing a cadmium(II) ion and an amino acid, white precipitates often appear in the test solution, and they disturb the emf measurements. Such precipitates were formes in the solutions, pH ranging 7.5--8.5, during the course of titrations of the test solutions containing cadmium(II) ion and amino acid such as glycine, α-alanine. 2-aminobutanoic acid, 3-aminobutanoic acid, 4-aminobutanoic acid, 2-aminopentanoic acid, 5-aminopentanoic acid, 2-aminohexanoic acid, 6-aminohexanoic acid, aspartic acid, glutamic acid, asparagine, or glutamine. The identification of the precipitates obtained from the solutions containing cadmium(II) ion and L-aspartic acid, 4-aminobutanoic acid, or 6-aminohexanoic acid were carried out by both of elemental analysis and the infrared spectroscopy. These results indicated that the precipitate obtained from the solution containing cadmium(II) ion and L-aspartic acid was 1:1 cadmium(II)-L-aspartic acid complex and did not contain any cadmium(II) hydroxide, and other two precipitates were mostly cadmium(II) hydroxide and contained a little cadmium(II)-amino acid complexes. (author)

Modeling cadmium in the feed chain and cattle organs

NARCIS (Netherlands)

Fels-Klerx, van der H.J.; Romkens, P.F.A.M.; Franz, E.; Raamsdonk, van L.W.D.

2011-01-01

The objectives of this study were to estimate cadmium contamination levels in different scenarios related to soil characteristics and assumptions regarding cadmium accumulation in the animal tissues, using quantitative supply chain modeling. The model takes into account soil cadmium levels, soil pH,

Antiviral therapy of hepatitis C in 2014: do we need resistance testing?

Science.gov (United States)

Schneider, Maximilian David; Sarrazin, Christoph

2014-05-01

The treatment of chronic hepatitis C has fundamentally changed since the approval of the first direct-acting antivirals (DAA) in 2011. In addition to telaprevir and boceprevir, in 2014 two new NS3 protease inhibitors (simeprevir and faldaprevir), one non-nucleoside polymerase inhibitor (sofosbuvir) and one NS5a replication complex inhibitor (daclatasvir) have expanded the treatment options for chronic hepatitis C. Resistance-associated variants (RAV) are naturally produced during the HCV life cycle. The frequency of RAVs within HCV quasispecies mainly depends on their replicational fitness. Variants conferring resistance to nucleos(t)ide analogues have not been detected, and the majority of NS3 protease-resistant variants are present at low frequencies (0.1-3%) before initiation of DAA-based therapies. However, the Q80K variant conferring resistance to simeprevir has been observed in 9-48% of untreated HCV genotype 1a-infected patients, leading to reduced SVR rates. Resistant variants are detectable in the majority of patients with treatment failure to NS3 protease inhibitor- or NS5a inhibitor-based antiviral therapy. Long-term follow-up studies by population-based sequence analysis have shown the disappearance of resistant variants in the majority of patients, with median times to loss of mutations of 4-64weeks. For the nucleotide analogue sofosbuvir, the emergence of the S282T resistant variant has been observed only in single patients, with reversion to wild-type within several weeks. Data are sparse on retreatment of patients with the same DAA or the same class of DAAs. However, retreatment with a different class of DAAs after failure of NS3 protease inhibitor-based therapy has been successful in small studies. This article forms part of a symposium in Antiviral Research on "Hepatitis C: next steps toward global eradication." Copyright © 2014 Elsevier B.V. All rights reserved.

Combined 5-FU and ChoKα inhibitors as a new alternative therapy of colorectal cancer: evidence in human tumor-derived cell lines and mouse xenografts.

Directory of Open Access Journals (Sweden)

Ana de la Cueva

Full Text Available Colorectal cancer (CRC is the third major cause of cancer related deaths in the world. 5-fluorouracil (5-FU is widely used for the treatment of colorectal cancer but as a single-agent renders low response rates. Choline kinase alpha (ChoKα, an enzyme that plays a role in cell proliferation and transformation, has been reported overexpressed in many different tumors, including colorectal tumors. ChoKα inhibitors have recently entered clinical trials as a novel antitumor strategy.ChoKα specific inhibitors, MN58b and TCD-717, have demonstrated a potent antitumoral activity both in vitro and in vivo against several tumor-derived cell line xenografts including CRC-derived cell lines. The effect of ChoKα inhibitors in combination with 5-FU as a new alternative for the treatment of colon tumors has been investigated both in vitro in CRC-tumour derived cell lines, and in vivo in mouse xenografts models. The effects on thymidilate synthase (TS and thymidine kinase (TK1 levels, two enzymes known to play an essential role in the mechanism of action of 5-FU, were analyzed by western blotting and quantitative PCR analysis. The combination of 5-FU with ChoKα inhibitors resulted in a synergistic effect in vitro in three different human colon cancer cell lines, and in vivo against human colon xenografts in nude mice. ChoKα inhibitors modulate the expression levels of TS and TK1 through inhibition of E2F production, providing a rational for its mechanism of action.Our data suggest that both drugs in combination display a synergistic antitumoral effect due to ChoKα inhibitors-driven modulation of the metabolization of 5-FU. The clinical relevance of these findings is strongly supported since TCD-717 has recently entered Phase I clinical trials against solid tumors.

Effect of cadmium on electron and energy transfer reactions in corn mitochondria

Energy Technology Data Exchange (ETDEWEB)

Miller, R J; Bittell, J E; Koeppe, D E

1973-01-01

The effects of cadmium on isolated corn shoot mitochondria were determined. In the absence of phosphate cadmium stimulated the oxidation of exogenous NADH optimally at 0.025 mM, but was inhibitory at 0.1 mM and above. The presence of phosphate negated the cadmium stimulation of exogenous NADH oxidation and permitted inhibitions only at higher cadmium concentrations. Succinate or malate + pyruvate oxidation in the absence of phosphate was inhibited to a greater extent by cadmium than when phosphate was present. ADP/O and respiratory control ratios were reduced by cadmium but generally were less sensitive to cadmium than state 4 or minus phosphate respiration. The data suggest that the site of cadmium effect is likely to be early in electron transport. Cadmium had a pronounced effect on mitochondrial swelling under either passive or active conditions. When succinate or exogenous NADH were being oxidized swelling occurred at 0.05 mM cadmium, but with malate + pyruvate the cadmium concentration had to exceed 1.0 mM. Phosphate (2 mM) prevented the swelling. Dithiothreitol, a SH group protector, prevented any effect of cadmium on swelling or respiration which suggests that sulfhydryl groups are likely involved in the cadmium-membrane interaction.

Cadmium Removal from Aqueous Solutions by Ground Pine Cone

Directory of Open Access Journals (Sweden)

H Izanloo, S Nasseri

2005-01-01

Full Text Available A study on the removal of cadmium ions from aqueous solutions by pine cone was conducted in batch conditions. Kinetic data and equilibrium removal isotherms were obtained. The influence of different experimental parameters such as contact time, initial concentration of cadmium, pine cone mass and particle size, and temperature on the kinetics of cadmium removal was studied. Results showed that the main parameters that played an important role in removal phenomenon were initial cadmium concentration, particle size and pine cone mass. The necessary time to reach equilibrium was between 4 and 7 hours based on the initial concentration of cadmium. The capacity of cadmium adsorption at equilibrium increased with the decrease of pine cone particle size. The capacity of cadmium adsorption at equilibrium by pine cone increased with the quantity of pine cone introduced (1–4 g/L. Temperature in the range of 20-30°C showed a restricted effect on the removal kinetics (13.56 mg/g at 20°C and a low capacity of adsorption about 11.48 mg/g at 30°C. The process followed pseudo second-order kinetics. The cadmium uptake of pine cone was quantitatively evaluated using adsorption isotherms. Results indicated that the Langmuir model gave a better fit to the experimental data in comparison with the Freundlich equation.

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