DARPA Antibody Technology Program. Standardized Test Bed for Antibody Characterization: Characterization of an MS2 ScFv Antibody Produced by Illumina

Science.gov (United States)

2016-08-01

ECBC-TR-1395 DARPA ANTIBODY TECHNOLOGY PROGRAM STANDARDIZED TEST BED FOR... ANTIBODY CHARACTERIZATION: CHARACTERIZATION OF AN MS2 SCFV ANTIBODY PRODUCED BY ILLUMINA Patricia E. Buckley Alena M. Calm Heather Welsh Roy...4. TITLE AND SUBTITLE DARPA Antibody Technology Program Standardized Test Bed for Antibody Characterization: Characterization of an MS2 ScFv

Vidyasagar, Dr Mathukumalli

Indian Academy of Sciences (India)

Elected: 1992 Section: Engineering & Technology ... Address: Cecil & Ida Green Chair of Systems Biology Science, Erik Jonsson School of Engineering & Computer Science, The University of Texas at Dallas, ... Upcoming Refresher Courses.

Racism, empire and sociology

OpenAIRE

Smith, Andrew

2017-01-01

Reviews of Gurminder K Bhambra, Connected Sociologies; Peo Hansen and Stefan Jonsson, Eurafrica: The Untold History of European Integration and Colonialism; Wulf D. Hund, Alana Lentin (eds) Racism and Sociology

Up-regulation of glutathione-related genes, enzyme activities and transport proteins in human cervical cancer cells treated with doxorubicin.

Science.gov (United States)

Drozd, Ewa; Krzysztoń-Russjan, Jolanta; Marczewska, Jadwiga; Drozd, Janina; Bubko, Irena; Bielak, Magda; Lubelska, Katarzyna; Wiktorska, Katarzyna; Chilmonczyk, Zdzisław; Anuszewska, Elżbieta; Gruber-Bzura, Beata

2016-10-01

Doxorubicin (DOX), one of the most effective anticancer drugs, acts in a variety of ways including DNA damage, enzyme inhibition and generation of reactive oxygen species. Glutathione (GSH) and glutathione-related enzymes including: glutathione peroxidase (GPX), glutathione reductase (GSR) and glutathione S-transferases (GST) may play a role in adaptive detoxification processes in response to the oxidative stress, thus contributing to drug resistance phenotype. In this study, we investigated effects of DOX treatment on expression and activity of GSH-related enzymes and multidrug resistance-associated proteins in cultured human cervical cancer cells displaying different resistance against this drug (HeLa and KB-V1). Determination of expression level of genes encoding GST isoforms and MRP proteins (GCS, GPX, GSR, GSTA1-3, GSTM1, GSTP1, ABCC1-3, MGST1-3) was performed using StellARray™ Technology. Enzymatic activities of GPX and GSR were measured using biochemical methods. Expression of MRP1 was examined by immunofluorescence microscopy. This study showed that native expression levels of GSTM1 and GSTA3 were markedly higher in KB-V1 cells (2000-fold and 200-fold) compared to HeLa cells. Resistant cells have also shown significantly elevated expression of GSTA1 and GSTA2 genes (200-fold and 50-fold) as a result of DOX treatment. In HeLa cells, exposure to DOX increased expression of all genes: GSTM1 (7-fold) and GSTA1-3 (550-fold, 150-fold and 300-fold). Exposure to DOX led to the slight increase of GCS expression as well as GPX activity in KB-V1 cells, while in HeLa cells it did not. Expression of ABCC1 (MRP1) was not increased in any of the tested cell lines. Our results indicate that expression of GSTM1 and GSTA1-3 genes is up-regulated by DOX treatment and suggest that activity of these genes may be associated with drug resistance of the tested cells. At the same time, involvement of MRP1 in DOX resistance in the given experimental conditions is unlikely

The virtual GULLIVER project

NARCIS (Netherlands)

Trappl, R.; Nijholt, Antinus; Stuk, M.; Zwiers, Jakob

2002-01-01

In this paper we discuss our virtual reality project Gulliver. This project is part of a more comprehensive project conceived by two artists, Matjaž Štuk and Alena Hudcovicová, called “Gulliver’s Museum of Living Art��?. Our part of the project involves a virtual reality version of Swift’s Gulliver

Enabling virtual communities: Gulliver and Aveiro

NARCIS (Netherlands)

Nijholt, Antinus; Faisal, K.; Sarfraz, M.

2002-01-01

In this paper we discuss two of our projects on virtual realities. First there is the virtual reality project Gulliver. This project is part of a more comprehensive project conceived by two artists, Matjaž Štuk and Alena Hudcovicová, called “Gulliver’s Museum of Living Art��?. Our part of the

Radford McAlester flight paths

Data.gov (United States)

U.S. Environmental Protection Agency — Heights and position of UAS from starting point. This dataset is associated with the following publication: Aurell, J., B. Mitchell, V. Chirayath, J. Jonsson, D....

Odešla Alena Šilhová

Czech Academy of Sciences Publication Activity Database

Boháčová, Ivana; Venclová, Natalie

2008-01-01

Roč. 60, č. 2 (2008), s. 348-348 ISSN 0323-1267 Institutional research plan: CEZ:AV0Z80020508 Keywords : conservation of archaeologicl objects * study of historical materials * methods of conservation Subject RIV: CA - Inorganic Chemistry

Tallinna tulevik - iseorganiseeruv metropol = Future of Tallinn - the self-organising metropolis / Panu Lehtovuori

Index Scriptorium Estoniae

Lehtovuori, Panu, 1968-

2009-01-01

Väljavõtteid Eesti Kunstiakadeemia 6. urbanistika ja linnamaastiku päevadel "Timewide" konverentsil peetud aruteludest Tallinna linnaehitusliku tuleviku teemadel. Arvamust avaldasid Masayo Ave (Jaapan), Tomas Jonsson (Kanada) ja Kalle Komissarov, vestlusringi juhtis Andres Kurg

Iskusstvo bumazhnogo lista / Galina Balashova

Index Scriptorium Estoniae

Balashova, Galina

2006-01-01

Tšehhi Vabariigi suursaatkonna vahendatud tšehhi graafika näitus "10 isiksust tšehhi graafikas" Eesti Rahvusraamatukogus. Tsehhi graafika ajaloost ja töödest näitusel. Esindatud on kunstnikud Eduard Ovèaèek, Kveta Pacovska, Alena Kuèerova, Mikolash Axman, Adolf Born, Ladislav €epelak, Jiri Shalamoun, Lubomir Paeibyl, Jaroslav Kralik ja Jiri Anderle

Endothelial glutathione-S-transferase A4-4 protects against oxidative stress and modulates iNOS expression through NF-κB translocation

International Nuclear Information System (INIS)

Yang Yongzhen; Yang Yusong; Xu Ya; Lick, Scott D.; Awasthi, Yogesh C.; Boor, Paul J.

2008-01-01

Our recent work in endothelial cells and human atherosclerotic plaque showed that overexpression of glutathione-S-tranferases (GSTs) in endothelium protects against oxidative damage from aldehydes such as 4-HNE. Nuclear factor (NF)-κB plays a crucial role during inflammation and immune responses by regulating the expression of inducible genes such as inducible nitric oxide synthase (iNOS). 4-HNE induces apoptosis and affects NF-κB mediated gene expression, but conflicting results on 4-HNE's effect on NF-κB have been reported. We compared the effect of 4-HNE on iNOS and the NF-κB pathway in control mouse pancreatic islet endothelial (MS1) cells and those transfected with mGSTA4, a α-class GST with highest activity toward 4-HNE. When treated with 4-HNE, mGSTA4-transfected cells showed significant upregulation of iNOS and nitric oxide (NO) through (NF)-κB (p65) translocation in comparison with wild-type or vector-transfected cells. Immunohistochemical studies of early human plaques showed lower 4-HNE content and upregulation of iNOS, which we take to indicate that GSTA4-4 induction acts as an enzymatic defense against high levels of 4-HNE, since 4-HNE accumulated in more advanced plaques, when detoxification and exocytotic mechanisms are likely to be overwhelmed. These studies suggest that GSTA4-4 may play an important defensive role against atherogenesis through detoxification of 4-HNE and upregulation of iNOS

Fouling kinetics in microfiltration of protein solutions using different membrane configurations

DEFF Research Database (Denmark)

Jakobsen, Sune; Jonsson, Gunnar Eigil

1997-01-01

Protein fouling in microfiltration has a large impact on the permeate flux and observed retention of the proteins despite the fact that the protein molecule is several times smaller than the average pore size in microfiltration membranes. This is due to adsorption and deposition of protein...... molecules and aggregates. The effect of membrane configuration upon protein fouling was investigated in crossflow filtration with asymmetric membranes either in a normal mode or in a reverse mode. It was observed by Jonsson et al. [1] that beer filtration in a reverse mode results in a smaller decrease...... in the flux compared to beer filtration in a normal mode. Similar results for protein filtration were observed by Bowen et al. [2]. One possible way to avoid fouling is the novel backshock technique (see Jonsson et al. [1]). The effect of backshock on protein filtration was investigated using a hollow fiber...

Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism

Directory of Open Access Journals (Sweden)

Xinmiao Yan

2016-03-01

Full Text Available Pyrrolizidine Alkaloids (PAs are currently one of the most important botanical hepatotoxic ingredients. Glutathion (GSH metabolism is the most reported pathway involved in hepatotoxicity mechanism of PAs. We speculate that, for different PAs, there should be a common mechanism underlying their hepatotoxicity in GSH metabolism. Computational methods were adopted to test our hypothesis in consideration of the limitations of current experimental approaches. Firstly, the potential targets of 22 PAs (from three major PA types in GSH metabolism were identified by reverse docking; Secondly, glutathione S-transferase A1 (GSTA1 and glutathione peroxidase 1 (GPX1 targets pattern was found to be a special characteristic of toxic PAs with stepwise multiple linear regressions; Furthermore, the molecular mechanism underlying the interactions within toxic PAs and these two targets was demonstrated with the ligand-protein interaction analysis; Finally, GSTA1 and GPX1 were proved to be significant nodes in GSH metabolism. Overall, toxic PAs could be identified by GSTA1 and GPX1 targets pattern, which suggests their common hepatotoxicity mechanism: the interfering of detoxication in GSH metabolism. In addition, all the strategies developed here could be extended to studies on toxicity mechanism of other toxins.

Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism.

Science.gov (United States)

Yan, Xinmiao; Kang, Hong; Feng, Jun; Yang, Yiyan; Tang, Kailin; Zhu, Ruixin; Yang, Li; Wang, Zhengtao; Cao, Zhiwei

2016-03-07

Pyrrolizidine Alkaloids (PAs) are currently one of the most important botanical hepatotoxic ingredients. Glutathion (GSH) metabolism is the most reported pathway involved in hepatotoxicity mechanism of PAs. We speculate that, for different PAs, there should be a common mechanism underlying their hepatotoxicity in GSH metabolism. Computational methods were adopted to test our hypothesis in consideration of the limitations of current experimental approaches. Firstly, the potential targets of 22 PAs (from three major PA types) in GSH metabolism were identified by reverse docking; Secondly, glutathione S-transferase A1 (GSTA1) and glutathione peroxidase 1 (GPX1) targets pattern was found to be a special characteristic of toxic PAs with stepwise multiple linear regressions; Furthermore, the molecular mechanism underlying the interactions within toxic PAs and these two targets was demonstrated with the ligand-protein interaction analysis; Finally, GSTA1 and GPX1 were proved to be significant nodes in GSH metabolism. Overall, toxic PAs could be identified by GSTA1 and GPX1 targets pattern, which suggests their common hepatotoxicity mechanism: the interfering of detoxication in GSH metabolism. In addition, all the strategies developed here could be extended to studies on toxicity mechanism of other toxins.

Electronic systems for the organization and planning of school

OpenAIRE

Vodová, Alena

2014-01-01

TITLE: Electronic systems for the organization and planning of school AUTHOR: Alena Vodová DEPARTMENT: The Center of School management SUPERVISOR: Ing. Petr Svoboda Ph.D. ABSTRACT: The bachelor thesis gives comprehensive overview electronic systems for organization and planning of school. Maps of species, describes their function, demonstrates the benefits, modes and applications to use in school. In the research part individuals system compares between them and validates their use in schools...

14 February 2012 - Vice-President of the Senate of the Parliament of the Czech Republic A. Gajduskova signing the guest book with CERN Director-General R. Heuer; visiting ATLAS experimental area with Collaboration Spokesperson F. Gianotti. Ambassador Sequensova to the UN accompanies the Vice-President.

CERN Document Server

Maximilien Brice

2012-01-01

Vice-president of the Senate of the Parliament of the Czech Republic, Alena Gajduskova was welcomed to CERN by Rolf Heuer, CERN’s director-general, on 14 and 15 February. Her time at CERN included the ATLAS Visitor Centre and underground experimental area, the LHC tunnel, the LHC superconducting-magnet test hall and the ALICE underground experimental area. She also heard a presentation on the LHC Computing Grid Project at CERN’s Computer Centre.

Induction of insulin and islet amyloid polypeptide production in pancreatic islet glucagonoma cells by insulin promoter factor 1

DEFF Research Database (Denmark)

Serup, P; Jensen, J; Andersen, F G

1996-01-01

Insulin promoter factor 1 (IPF1), a member of the homeodomain protein family, serves an early role in pancreas formation, as evidenced by the lack of pancreas formation in mice carrying a targeted disruption of the IPF1 gene [Jonsson, J., Carlsson, L., Edlund, T. & Edlund, H. (1994) Nature (London...

Mongolský tanec

OpenAIRE

Fritscherová, Jana

2015-01-01

Tittle: Mongolian dance Author: Jana Fritscherová Supervisor: PhDr. Alena Oberfalzerová, Ph.D. The current work deals with dances on the territory of Mongolia. It focuses in particular on the Biyelgee dance. Interviews from the field research are included in the work to better illustrate the Mongolian way of thinking concerning the concept of the dance. A very important subchapter features dance description, in which selected typed of Mongolian dances are specifically concerned. The work also...

Novel biomarkers of mercury-induced autoimmune dysfunction: a Cross-sectional study in Amazonian Brazil

Science.gov (United States)

Motts, Jonathan A.; Shirley, Devon L.; Silbergeld, Ellen K.; Nyland, Jennifer F.

2014-01-01

Mercury is an ubiquitous environmental contaminant, causing both neurotoxicity and immunotoxicity. Given its ability to amalgamate gold, mercury is frequently used in small-scale artisanal gold mining. We have previously reported that elevated serum titers of antinuclear autoantibodies (ANA) are associated with mercury exposures of miners in gold mining. The goal of this project was to identify novel serum biomarkers of mercury-induced immunotoxicity and autoimmune dysregulation. We conducted an analysis of serum samples from a cross-sectional epidemiological study on miners working in Amazonian Brazil. In proteomic screening analyses, samples were stratified based on mercury concentrations and ANA titer and a subset of serum samples (N=12) were profiled using Immune Response Biomarker Profiling ProtoArray protein microarray for elevated autoantibodies. Of the up-regulated autoantibodies in the mercury-exposed cohort, potential target autoantibodies were selected based on relevance to pro-inflammatory and macrophage activation pathways. ELISAs were developed to test the entire sample cohort (N=371) for serum titers to the highest of these autoantibodies (anti-glutathione S-transferase alpha, GSTA1) identified in the high mercury/high ANA group. We found positive associations between elevated mercury exposure and up-regulated serum titers of 3760 autoantibodies as identified by ProtoArray. Autoantibodies identified as potential novel biomarkers of mercury-induced immunotoxicity include antibodies to the following proteins: GSTA1, tumor necrosis factor ligand superfamily member 13, linker for activation of T cells, signal peptide peptidase like 2B, stimulated by retinoic acid 13, and interferon induced transmembrane protein. ELISA analyses confirmed that mercury-exposed gold miners had significantly higher serum titers of anti-GSTA1 autoantibody [unadjusted odds ratio = 89.6; 95% confidence interval: 27.2, 294.6] compared to emerald miners (referent population

Aktivity žáků konkrétní školy k ochraně životního prostředí

OpenAIRE

Malý, Tomáš

2015-01-01

Title: Activities of pupils of specifis school for enviromental protection Author: Tomáš Malý Department of Pedagogy Supervisor: PhDr. Alena Thorovská Abstract: Theme of this work is project of teaching environmental education in two-year practical school. This essay is outlining some problems with project education and possibilities of pupils of practical school in this area. Intention of this essay is to describe how we can apply environmental education in the form of simple projects which ...

The need for peri-operative supplemental oxygen | Chikungwa ...

African Journals Online (AJOL)

The need for peri-operative supplemental oxygen. M. T. Chikungwa, K. Jonsson. Abstract. (Central African Journal of Medicine: 2002 48 (5-6): 72-73). AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of Use ...

The regional energy integration: the latin-american experiences; L'integration energetique regionale: les experiences latino-americaines

Energy Technology Data Exchange (ETDEWEB)

NONE

2003-07-01

The ways of the regional economic integrations are not identical and generate different repercussions on the markets and the energy industries evolution. The example of the Latin America proposes many various experiences to evaluate the stakes and the limits of each regional integrations. These limits lead to solution researches including indisputable convergencies. The first part of this document presents the genesis of these regional economic integrations experiences in Latina America, to study in the second part the energy consequences of the liberal ALENA and of the more political MERCOSUR. (A.L.B.)

The regional energy integration: the latin-american experiences

International Nuclear Information System (INIS)

2003-01-01

The ways of the regional economic integrations are not identical and generate different repercussions on the markets and the energy industries evolution. The example of the Latin America proposes many various experiences to evaluate the stakes and the limits of each regional integrations. These limits lead to solution researches including indisputable convergencies. The first part of this document presents the genesis of these regional economic integrations experiences in Latina America, to study in the second part the energy consequences of the liberal ALENA and of the more political MERCOSUR. (A.L.B.)

The regional energy integration: the latin-american experiences; L'integration energetique regionale: les experiences latino-americaines

Energy Technology Data Exchange (ETDEWEB)

NONE

2003-07-01

The ways of the regional economic integrations are not identical and generate different repercussions on the markets and the energy industries evolution. The example of the Latin America proposes many various experiences to evaluate the stakes and the limits of each regional integrations. These limits lead to solution researches including indisputable convergencies. The first part of this document presents the genesis of these regional economic integrations experiences in Latina America, to study in the second part the energy consequences of the liberal ALENA and of the more political MERCOSUR. (A.L.B.)

Increased sensitivity of Hep G2 cells toward the cytotoxicity of cisplatin by the treatment of piper betel leaf extract.

Science.gov (United States)

Young, Shun-Chieh; Wang, Chau-Jong; Hsu, Jeng-Dong; Hsu, Jui-Ling; Chou, Fen-Pi

2006-06-01

Piper betel leaves (PBL) are used in Chinese folk medicine for the treatment of various disorders. PBL has the biological capabilities of de-toxication, anti-oxidation and anti-mutation. In this study we first examined the effect of PBL extract on the activity of Glutathione S-transferase (GST) isoforms, and found that it inhibited total GST and the alpha class of GST (GSTA), but not the pi class of GST (GSTP), and the mu class of GST (GSTM), activity in Hep G2 cells. RT-PCR results verified a reduction in the expression of GSTA1. Next, we examined whether PBL extract could increase the sensitivity of Hep G2 cells to anti-cancer drugs. The data showed that the cytotoxicity of cisplatin was significantly enhanced by the presence of PBL extract, accompanied by a reduction in the expression of multidrug resistance protein 2 (MRP2). These effects of PBL extract were compared to its major constitute, eugenol. Although eugenol decreased MRP2 level more effectively than PBL extract, it exhibited less sensitizing effect. In conclusion, we demonstrated that PBL extract was able to increase the sensitivity of Hep G2 cells to cisplatin via at least two mechanisms, reducing the expression of MRP2 and inhibiting the activity of total GST and the expression of GSTA. The data of this study support an application of PBL as an additive to reduce drug resistance.

The Genetic Architecture of Murine Glutathione Transferases.

Directory of Open Access Journals (Sweden)

Lu Lu

Full Text Available Glutathione S-transferase (GST genes play a protective role against oxidative stress and may influence disease risk and drug pharmacokinetics. In this study, massive multiscalar trait profiling across a large population of mice derived from a cross between C57BL/6J (B6 and DBA2/J (D2--the BXD family--was combined with linkage and bioinformatic analyses to characterize mechanisms controlling GST expression and to identify downstream consequences of this variation. Similar to humans, mice show a wide range in expression of GST family members. Variation in the expression of Gsta4, Gstt2, Gstz1, Gsto1, and Mgst3 is modulated by local expression QTLs (eQTLs in several tissues. Higher expression of Gsto1 in brain and liver of BXD strains is strongly associated (P < 0.01 with inheritance of the B6 parental allele whereas higher expression of Gsta4 and Mgst3 in brain and liver, and Gstt2 and Gstz1 in brain is strongly associated with inheritance of the D2 parental allele. Allele-specific assays confirmed that expression of Gsto1, Gsta4, and Mgst3 are modulated by sequence variants within or near each gene locus. We exploited this endogenous variation to identify coexpression networks and downstream targets in mouse and human. Through a combined systems genetics approach, we provide new insight into the biological role of naturally occurring variants in GST genes.

Expression of proliferative and inflammatory markers in a full-thickness human skin equivalent following exposure to the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide

International Nuclear Information System (INIS)

Black, Adrienne T.; Hayden, Patrick J.; Casillas, Robert P.; Heck, Diane E.; Gerecke, Donald R.; Sinko, Patrick J.; Laskin, Debra L.; Laskin, Jeffrey D.

2010-01-01

Sulfur mustard is a potent vesicant that induces inflammation, edema and blistering following dermal exposure. To assess molecular mechanisms mediating these responses, we analyzed the effects of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide, on EpiDerm-FT TM , a commercially available full-thickness human skin equivalent. CEES (100-1000 μM) caused a concentration-dependent increase in pyknotic nuclei and vacuolization in basal keratinocytes; at high concentrations (300-1000 μM), CEES also disrupted keratin filament architecture in the stratum corneum. This was associated with time-dependent increases in expression of proliferating cell nuclear antigen, a marker of cell proliferation, and poly(ADP-ribose) polymerase (PARP) and phosphorylated histone H2AX, markers of DNA damage. Concentration- and time-dependent increases in mRNA and protein expression of eicosanoid biosynthetic enzymes including COX-2, 5-lipoxygenase, microsomal PGE 2 synthases, leukotriene (LT) A 4 hydrolase and LTC 4 synthase were observed in CEES-treated skin equivalents, as well as in antioxidant enzymes, glutathione S-transferases A1-2 (GSTA1-2), GSTA3 and GSTA4. These data demonstrate that CEES induces rapid cellular damage, cytotoxicity and inflammation in full-thickness skin equivalents. These effects are similar to human responses to vesicants in vivo and suggest that the full thickness skin equivalent is a useful in vitro model to characterize the biological effects of mustards and to develop potential therapeutics.

Increased oxidative stress and antioxidant expression in mouse keratinocytes following exposure to paraquat

International Nuclear Information System (INIS)

Black, Adrienne T.; Gray, Joshua P.; Shakarjian, Michael P.; Laskin, Debra L.; Heck, Diane E.; Laskin, Jeffrey D.

2008-01-01

Paraquat (1,1'-dimethyl-4,4'-bipyridinium) is a widely used herbicide known to induce skin toxicity. This is thought to be due to oxidative stress resulting from the generation of cytotoxic reactive oxygen intermediates (ROI) during paraquat redox cycling. The skin contains a diverse array of antioxidant enzymes which protect against oxidative stress including superoxide dismutase (SOD), catalase, glutathione peroxidase-1 (GPx-1), heme oxygenase-1 (HO-1), metallothionein-2 (MT-2), and glutathione-S-transferases (GST). In the present studies we compared paraquat redox cycling in primary cultures of undifferentiated and differentiated mouse keratinocytes and determined if this was associated with oxidative stress and altered expression of antioxidant enzymes. We found that paraquat readily undergoes redox cycling in both undifferentiated and differentiated keratinocytes, generating superoxide anion and hydrogen peroxide as well as increased protein oxidation which was greater in differentiated cells. Paraquat treatment also resulted in increased expression of HO-1, Cu,Zn-SOD, catalase, GSTP1, GSTA3 and GSTA4. However, no major differences in expression of these enzymes were evident between undifferentiated and differentiated cells. In contrast, expression of GSTA1-2 was significantly greater in differentiated relative to undifferentiated cells after paraquat treatment. No changes in expression of MT-2, Mn-SOD, GPx-1, GSTM1 or the microsomal GST's mGST1, mGST2 and mGST3, were observed in response to paraquat. These data demonstrate that paraquat induces oxidative stress in keratinocytes leading to increased expression of antioxidant genes. These intracellular proteins may be important in protecting the skin from paraquat-mediated cytotoxicity

Global deletion of glutathione S-Transferase A4 exacerbates developmental nonalcoholic steatohepatitis

Science.gov (United States)

We established a mouse model of developmental nonalcoholic steatohepatitis (NASH) by feeding a high polyunsaturated fat liquid diet to female glutathione-S-transferase 4-4 (Gsta4-/-)/peroxisome proliferator activated receptor a (Ppara-/-) double knockout 129/SvJ mice for 12 weeks from weaning. We us...

Does maternal exposure to artificial food coloring additives increase oxidative stress in the skin of rats?

Science.gov (United States)

Başak, K; Başak, P Y; Doğuç, D K; Aylak, F; Oğuztüzün, S; Bozer, B M; Gültekin, F

2017-10-01

Glutathione-S-transferase (GST) and cytochrome P450 family 1 subfamily A polypeptide 1 (CYP1A1) metabolize and detoxify carcinogens, drugs, environmental pollutants, and reactive oxygen species. Changes of GST expression in tissues and gene mutations have been reported in association with many neoplastic skin diseases and dermatoses. Widely used artificial food coloring additives (AFCAs) also reported to effect primarily behavioral and cognitive function and cause neoplastic diseases and several inflammatory skin diseases. We aimed to identify the changes in expression of GSTs, CYP1A1, and vascular endothelial growth factor (VEGF) in rat skin which were maternally exposed AFCAs. A rat model was designed to evaluate the effects of maternal exposure of AFCAs on skin in rats. "No observable adverse effect levels" of commonly used AFCAs as a mixture were given to female rats before and during gestation. Immunohistochemical expression of GSTs, CYP1A1, and VEGF was evaluated in their offspring. CYP1A1, glutathione S-transferase pi (GSTP), glutathione S-transferase alpha (GSTA), glutathione S-transferase mu (GSTM), glutathione S-transferase theta (GSTT), and VEGF were expressed by epidermal keratinocytes, dermal fibroblasts, sebaceous glands, hair follicle, and subcutaneous striated muscle in the normal skin. CYP1A1, GSTA, and GSTT were expressed at all microanatomical sites of skin in varying degrees. The expressions of CYP1A1, GSTA, GSTT, and VEGF were decreased significantly, while GSTM expression on sebaceous gland and hair follicle was increased. Maternal exposure of AFCAs apparently effects expression of the CYP1A1, GSTs, and VEGF in the skin. This prominent change of expressions might play role in neoplastic and nonneoplastic skin diseases.

Accounting information and managerial work

OpenAIRE

Matthew Hall

2010-01-01

Despite calls to link management accounting more closely to management (Jonsson, 1998), much is still to be learned about the role of accounting information in managerial work. This lack of progress stems partly from a failure to incorporate in research efforts the findings regarding the nature of managerial work, as well as inadequate attention devoted to the detailed practices through which accounting information is actually used by managers in their work. In this paper I draw on prior rese...

Aircraft Observations for Improved Physical Parameterization for Seasonal Prediction

Science.gov (United States)

2013-09-30

platform is ready for use in air-sea interaction research projects. RELATED PROJECTS None PUBLICATIONS Gerber H., G. Frick, S. Malinowski ... Malinowski , S. P., H. Gerber, I. Jen-LaPlante, M. K. Kopec, W. Kumala, K. Nurowska, P. Y. Chuang, K. E. Haman, D. D. Khelif, S. K. Krueger, and H. H. Jonsson...Haman, K. E., Kopec, M. K., Khelif, D., and Malinowski , S. P.: Modified ultrafast thermometer UFT-M and temperature measurements during Physics of

Désagrarisation de l’économie paysanne et « refonctionnalisation » de la localité rurale au Mexique

OpenAIRE

Léonard, Éric; Palma, Rafael

2017-01-01

Le travail présenté ici se propose d’analyser les modalités de recomposition des espaces ruraux mexicains dans le cadre de la ratification du Traité de libre-échange avec les États-Unis et le Canada (Alena). On assiste ainsi à la recomposition et à la mise en réseau de certains territoires autour des filières de production, conditionnement et mise en marché de produits frais à forte intensité en travail et capital. L’enquête porte plus particulièrement sur la région des Tuxtlas, au sud de l’É...

Polymorphisms in heterocyclic aromatic amines metabolism-related genes are associated with colorectal adenoma risk.

Science.gov (United States)

Eichholzer, Monika; Rohrmann, Sabine; Barbir, Aline; Hermann, Silke; Teucher, Birgit; Kaaks, Rudolf; Linseisen, Jakob

2012-01-01

Colorectal adenoma (CRA) and colorectal cancer (CRC) risks have been linked to the intake of red and processed meat. Heterocyclic aromatic amines (HCA) formed herein during high temperature cooking, are metabolized by a variety of enzymes, and allelic variation in the coding genes could influence individual CRA risk. Associations of polymorphisms in NAT1, NAT2, GSTA1, SULT1A1, CYP1A2, UGT1A7, UGT1A9, GSTP1 genes with colorectal adenoma risk were investigated in a nested case-control study of the EPIC-Heidelberg cohort including 428 cases matched by age, sex and year of recruitment with one or two controls (n=828) with negative colonoscopy per case. Genoyping was preformed with the Sequenom MassArray system and the LightCycler 480. Conditional logistic regression was used to compute odds ratios (OR) and corresponding 95% confidence intervals (CI). For rs15561 (NAT1) and rs1057126 (NAT1), the rarer allel was significantly inversely associated with adenoma risk OR=0.80 (95% CI 0.65-0.97) and (OR=0.81 (95% CI 0.65-0.99) and, respectively). For the combined NAT2 alleles encoding for enzymes with medium (versus slow) activity we also observed a significantly inverse association with adenoma risk (OR=0.75; 95% CI 0.85-0.97). In addition, homozygous carriers of the A allele of rs3957357 (GSTA1), i.e., those with a decreased enzyme activity, had a decreased risk of colorectal adenoma with an OR of 0.68 (95% CI 0.50-0.92; AA versus GG/GA). Polymorphisms in the other tested genes did not modify the risk of colorectal adenomas. In conclusion, polymorphisms in NAT1, NAT2, and GSTA1 are related to colorectal adenoma risk in this German cohort.

Cytotoxic and Antitumor Effects of Curzerene from Curcuma longa.

Science.gov (United States)

Wang, Youdi; Li, Jiahong; Guo, Jiquan; Wang, Qiyou; Zhu, Shuguang; Gao, Siyuan; Yang, Chen; Wei, Min; Pan, Xuediao; Zhu, Wei; Ding, Dongmei; Gao, Ruiping; Zhang, Wei; Wang, Junye; Zang, Linquan

2017-01-01

Curzerene is a sesquiterpene and component used in oriental medicine. It was originally isolated from the traditional Chinese herbal medicine Curcuma rhizomes. In this study, anticancer activity of curzerene was examined in both in vitro and in vivo models. The result of the MTT assay showed that curzerene exhibited antiproliferative effects in SPC-A1 human lung adenocarcinoma cells in a time-dependent and dose-dependent manner. The anticancer IC 50 s were 403.8, 154.8, and 47.0 µM for 24, 48, and 72 hours, respectively. The flow cytometry analysis indicated curzerene arrested the cells in the G2/M cell cycle and promoted or induced apoptosis of SPC-A1 cells. The percentage of cells arrested in the G2/M phase increased from 9.26 % in the control group cells to 17.57 % in the cells treated with the highest dose (100 µM) of curzerene. Western blot and RT-PCR analysis demonstrated that curzerene induced the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Tumor growth was significantly inhibited in SPC-A1 cell-bearing nude mice by using curzerene (135 mg/kg daily), meanwhile, curzerene did not significantly affect body mass and the organs of the mice, which may indicate that curzerene has limited toxicity and side effects in vivo . In conclusion, curzerene could inhibit the proliferation of SPC-A1 human lung adenocarcinoma cells line in both in vitro and in vivo models. Focusing on its relationship with GSTA1, curzerene could induce the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Curzerene might be used as an anti-lung adenocarcinoma drug candidate compound for further development. Georg Thieme Verlag KG Stuttgart · New York.

CERN Expenditure Tracking: an improved financial tool for the LHC era

CERN Multimedia

Maximilien Brice

2002-01-01

In order to face the challenges of the LHC era, and following the recommendations of the External Review Committee, CERN Expenditure Tracking (CET) will soon replace the Budget Holders' Toolkit (BHT) application as a versatile and user-friendly way to view CERN financial data. It will offer significantly more functionality than BHT. Pictured here is the team in Administrative Services division responsible for developing CET. From left to right: (standing) Per Gunnar Jonsson, James Purvis, Mikael Angberg; (seated) Martyn Rankin, David McGlashan.

Enzymatic Detoxication, Conformational Selection, and the Role of Molten Globule Active Sites*

Science.gov (United States)

Honaker, Matthew T.; Acchione, Mauro; Zhang, Wei; Mannervik, Bengt; Atkins, William M.

2013-01-01

The role of conformational ensembles in enzymatic reactions remains unclear. Discussion concerning “induced fit” versus “conformational selection” has, however, ignored detoxication enzymes, which exhibit catalytic promiscuity. These enzymes dominate drug metabolism and determine drug-drug interactions. The detoxication enzyme glutathione transferase A1–1 (GSTA1–1), exploits a molten globule-like active site to achieve remarkable catalytic promiscuity wherein the substrate-free conformational ensemble is broad with barrierless transitions between states. A quantitative index of catalytic promiscuity is used to compare engineered variants of GSTA1–1 and the catalytic promiscuity correlates strongly with characteristics of the thermodynamic partition function, for the substrate-free enzymes. Access to chemically disparate transition states is encoded by the substrate-free conformational ensemble. Pre-steady state catalytic data confirm an extension of the conformational selection model, wherein different substrates select different starting conformations. The kinetic liability of the conformational breadth is minimized by a smooth landscape. We propose that “local” molten globule behavior optimizes detoxication enzymes. PMID:23649628

We won a National award

International Nuclear Information System (INIS)

Meciarova, A.; Cicova, V.

2011-01-01

On the occasion of the 43 rd conference for water management in the industry results of the 3 rd competition were announced for the National Business Award for Environment in the Slovak Republic 2011 organized by the Association of Industrial Ecology in Slovakia (ASPEK). The first prize in the category 'product; went to the hands of Slovenske elektrarne representatives for providing the energy self-sufficiency of Tery Chalet, High Tatras, all year round with installing photovoltaic system. 'We have a complex programme of five energies through which we support culture, sports, humanity, education and environmental protection. Hence we try to support constant sustainability of biodiversity,' underlined Alena Meciarova, Manager of Environment at Slovenske elektrarne. (author)

Robust Speech Processing & Recognition: Speaker ID, Language ID, Speech Recognition/Keyword Spotting, Diarization/Co-Channel/Environmental Characterization, Speaker State Assessment

Science.gov (United States)

2015-10-01

Dallas Erik Jonsson School of Engineering & Computer Science EC32 P.O. Box 830688 Richardson, Texas 75083-0688 8. PERFORMING ORGANIZATION REPORT...87 4.3 Whisper Based Processing for ASR ………………………………………….…. 92 5.0 Task 5: SPEAKER STATE ASSESSMENT/ ENVIROMENTAL SNIFFING (SSA/ENVS...Dec. 7-10, 2014 [3] S. Amuda, H. Boril, A. Sangwan, J.H.L. Hansen, T.S. Ibiyemi, “ Engineering analysis and recognition of Nigerian English: An

Functional Characterization and Expression of Molluscan Detoxification Enzymes and Transporters Involved in Dietary Allelochemical Resistance

Science.gov (United States)

2008-06-01

melanogasrer (43), and Homo sapiens (40) (Ding et al. 2003). To date, seven soluble cytosolic GST classes, encoding proteins of approximately 200 amino acids...Fasciola hepatica (P56598), Haliotis discus discus (ABF67506, ABF67507), Haemaphysalis longicornis (AAQ74441), Homo sapiens (NP_665683, AAV38750, NP_000840...MorciTa 2003 Mtilus Mdulis Western blot Jonsson ct al. 2004 CYP2H Mtilus go/lh,-ro/ii Western blot Peters el al. 19 9 0a (Y P2 Mvti/us ’dlis Western blot

A covariant formalism of spin precession with respect to a reference congruence

International Nuclear Information System (INIS)

Jonsson, Rickard

2006-01-01

We derive an effectively three-dimensional relativistic spin precession formalism. The formalism is applicable to any spacetime where an arbitrary timelike reference congruence of worldlines is specified. We employ what we call a stopped spin vector which is the spin vector that we would get if we momentarily make a pure boost of the spin vector to stop it relative to the congruence. Starting from the Fermi transport equation for the standard spin vector we derive a corresponding transport equation for the stopped spin vector. Employing a spacetime transport equation for a vector along a worldline, corresponding to spatial parallel transport with respect to the congruence, we can write down a precession formula for a gyroscope relative to the local spatial geometry defined by the congruence. This general approach has already been pursued by Jantzen et al (see e.g. Jantzen R T, Carini P and Bini D 1992 Ann. Phys. 215 1-50), but the algebraic form of our respective expressions differs. We are also applying the formalism to a novel type of spatial parallel transport introduced in Jonsson (2006 Class. Quantum Grav. 23 1), as well as verifying the validity of the intuitive approach of a forthcoming paper (Jonsson 2006 forthcoming) where gyroscope precession is explained entirely as a double Thomas type of effect. We also present the resulting formalism in explicit three-dimensional form (using the boldface vector notation), and give examples of applications

Influence of using date-specific values when extracting phenological metrics from 8-day composite NDVI data

CSIR Research Space (South Africa)

Bachoo, A

2007-07-01

Full Text Available ): this is the integral under the NDVI curve. Due to the contribution of bare soil to NDVI, a value of 0.1 instead of 0 was used as the minimum NDVI value (zero production). C. Algorithm parameters The parameters specified for the different algorithms were..., “Atmospheric correction of modis data in the visible to middle infrared- First results,” Remote Sensing of Enviroment, vol. 83, pp. 97–111, 2002. [3] P. Jonsson and L. Eklundh, “Seasonality extraction by function fitting to time-series of satellite sensor...

Glutathione S-transferase expression and isoenzyme composition during cell differentiation of Caco-2 cells

International Nuclear Information System (INIS)

Scharmach, E.; Hessel, S.; Niemann, B.; Lampen, A.

2009-01-01

The human colon adenocarcinoma cell line Caco-2 is frequently used to study human intestinal metabolism and transport of xenobiotica. Previous studies have shown that both Caco-2 cells and human colon cells constitutively express the multigene family of detoxifying enzymes glutathione S-transferases (GSTs), particularly GST alpha and GST pi. GSTs may play a fundamental role in the molecular interplay between phase I, II enzymes and ABC-transporters. The gut fermentation product, butyrate, can modulate the potential for detoxification. The aim of this study was to investigate the basal expression of further cytosolic GSTs in Caco-2 cells during cell differentiation. In addition, a comparison was made with expression levels in MCF-7 and HepG2, two other cell types with barrier functions. Finally, the butyrate-mediated modulation of gene and protein expression was determined by real time PCR and western blot analysis. In Caco-2, gene and protein expression levels of GST alpha increased during cell differentiation. High levels of GSTO1 and GSTP1 were constantly expressed. No expression of GSTM5 and GSTT1 was detected. HepG2 expressed GSTO1 and MCF-7 GSTZ1 most intensively. No expression of GSTA5, GSTM5, or GSTP1 was detected in either cell. Incubation of Caco-2 cells with butyrate (5 mM) significantly induced GSTA1 and GSTM2 in proliferating Caco-2 cells. In differentiated cells, butyrate tended to increase GSTO1 and GSTP1. The results of this study show that a differentiation-dependent expression of GSTs in Caco-2 cells may reflect the in vivo situation and indicate the potential of butyrate to modify intestinal metabolism. GSTA1-A4 have been identified as good markers for cell differentiation. The Caco-2 cell line is a useful model for assessing the potential of food-related substances to modulate the GST expression pattern.

Introducing the "TCDD-inducible AhR-Nrf2 gene battery".

Science.gov (United States)

Yeager, Ronnie L; Reisman, Scott A; Aleksunes, Lauren M; Klaassen, Curtis D

2009-10-01

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces genes via the transcription factor aryl hydrocarbon receptor (AhR), including Cyp1a1, NAD(P)H:quinone oxidoreductase 1 (Nqo1), UDP-glucuronosyltransferase 1a6 (Ugt1a6), and glutathione S-transferase a1 (Gsta1). These genes are referred to as the "AhR gene battery." However, Nqo1 is also considered a prototypical target gene of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). In mice, TCDD induction of Nrf2 and Nrf2 target, Nqo1, is dependent on AhR, and thus TCDD induction of drug-processing genes may be routed through an AhR-Nrf2 sequence. There has been speculation that Nrf2 may be involved in the TCDD induction of drug-processing genes; however, the data are not definitive. Therefore, to address whether TCDD induction of Nqo1, Ugts, and Gsts is dependent on Nrf2, we conducted the definitive experiment by administering TCDD (50 mug/kg, ip) to Nrf2-null and wild-type (WT) mice and collecting livers 24 h later to quantify the mRNA of drug-processing genes. TCDD induction of Cyp1a1 and Ugt1a1 was similar in WT and Nrf2-null mice, whereas TCDD induction of Ugt1a5 and 1a9 was blunted in Nrf2-null mice. TCDD induced Nqo1, Ugt1a6, 2b34, 2b35, 2b36, UDP-glucuronic acid-synthesizing gene UDP-glucose dehydrogenase, and Gsta1, m1, m2, m3, m6, p2, t2, and microsomal Gst1 in WT mice but not in Nrf2-null mice. Therefore, the present study demonstrates the novel finding that Nrf2 is required for TCDD induction of classical AhR battery genes Nqo1, Ugt1a6, and Gsta1, as well as most Ugt and Gst isoforms in livers of mice.

Glutathione S-transferase expression and isoenzyme composition during cell differentiation of Caco-2 cells.

Science.gov (United States)

Scharmach, E; Hessel, S; Niemann, B; Lampen, A

2009-11-30

The human colon adenocarcinoma cell line Caco-2 is frequently used to study human intestinal metabolism and transport of xenobiotica. Previous studies have shown that both Caco-2 cells and human colon cells constitutively express the multigene family of detoxifying enzymes glutathione S-transferases (GSTs), particularly GST alpha and GST pi. GSTs may play a fundamental role in the molecular interplay between phase I, II enzymes and ABC-transporters. The gut fermentation product, butyrate, can modulate the potential for detoxification. The aim of this study was to investigate the basal expression of further cytosolic GSTs in Caco-2 cells during cell differentiation. In addition, a comparison was made with expression levels in MCF-7 and HepG2, two other cell types with barrier functions. Finally, the butyrate-mediated modulation of gene and protein expression was determined by real time PCR and western blot analysis. In Caco-2, gene and protein expression levels of GST alpha increased during cell differentiation. High levels of GSTO1 and GSTP1 were constantly expressed. No expression of GSTM5 and GSTT1 was detected. HepG2 expressed GSTO1 and MCF-7 GSTZ1 most intensively. No expression of GSTA5, GSTM5, or GSTP1 was detected in either cell. Incubation of Caco-2 cells with butyrate (5 mM) significantly induced GSTA1 and GSTM2 in proliferating Caco-2 cells. In differentiated cells, butyrate tended to increase GSTO1 and GSTP1. The results of this study show that a differentiation-dependent expression of GSTs in Caco-2 cells may reflect the in vivo situation and indicate the potential of butyrate to modify intestinal metabolism. GSTA1-A4 have been identified as good markers for cell differentiation. The Caco-2 cell line is a useful model for assessing the potential of food-related substances to modulate the GST expression pattern.

Between Russia and Estonia: narratives of place in a new borderland / Alena Pfoser

Index Scriptorium Estoniae

Pfoser, Alena

2014-01-01

Artikkel käsitleb Eesti ja Venemaa piiri läheduses elavaid inimesi – kuidas nad mõtestavad kohta, kus nad elavad, kuidas nad tajuvad viimastel kümnenditel aset leidnud muutusi, millist mõju avaldab neile nõukogulik minevik jne. Aluseks Narvas ja Ivangorodis teostatud etnograafilised välitööd aastatel 2011-2012

Epitopes of MUC1 Tandem Repeats in Cancer as Revealed by Antibody Crystallography: Toward Glycopeptide Signature-Guided Therapy

Directory of Open Access Journals (Sweden)

Dapeng Zhou

2018-05-01

Full Text Available Abnormally O-glycosylated MUC1 tandem repeat glycopeptide epitopes expressed by multiple types of cancer have long been attractive targets for therapy in the race against genetic mutations of tumor cells. Glycopeptide signature-guided therapy might be a more promising avenue than mutation signature-guided therapy. Three O-glycosylated peptide motifs, PDTR, GSTA, and GVTS, exist in a tandem repeat HGVTSAPDTRPAPGSTAPPA, containing five O-glycosylation sites. The exact peptide and sugar residues involved in antibody binding are poorly defined. Co-crystal structures of glycopeptides and respective monoclonal antibodies are very few. Here we review 3 groups of monoclonal antibodies: antibodies which only bind to peptide portion, antibodies which only bind to sugar portion, and antibodies which bind to both peptide and sugar portions. The antigenicity of peptide and sugar portions of glyco-MUC1 tandem repeat were analyzed according to available biochemical and structural data, especially the GSTA and GVTS motifs independent from the most studied PDTR. Tn is focused as a peptide-modifying residue in vaccine design, to induce glycopeptide-binding antibodies with cross reactivity to Tn-related tumor glycans, but not glycans of healthy cells. The unique requirement for the designs of antibody in antibody-drug conjugate, bi-specific antibodies, and chimeric antigen receptors are also discussed.

Protein Carbonylation and Adipocyte Mitochondrial Function*

Science.gov (United States)

Curtis, Jessica M.; Hahn, Wendy S.; Stone, Matthew D.; Inda, Jacob J.; Droullard, David J.; Kuzmicic, Jovan P.; Donoghue, Margaret A.; Long, Eric K.; Armien, Anibal G.; Lavandero, Sergio; Arriaga, Edgar; Griffin, Timothy J.; Bernlohr, David A.

2012-01-01

Carbonylation is the covalent, non-reversible modification of the side chains of cysteine, histidine, and lysine residues by lipid peroxidation end products such as 4-hydroxy- and 4-oxononenal. In adipose tissue the effects of such modifications are associated with increased oxidative stress and metabolic dysregulation centered on mitochondrial energy metabolism. To address the role of protein carbonylation in the pathogenesis of mitochondrial dysfunction, quantitative proteomics was employed to identify specific targets of carbonylation in GSTA4-silenced or overexpressing 3T3-L1 adipocytes. GSTA4-silenced adipocytes displayed elevated carbonylation of several key mitochondrial proteins including the phosphate carrier protein, NADH dehydrogenase 1α subcomplexes 2 and 3, translocase of inner mitochondrial membrane 50, and valyl-tRNA synthetase. Elevated protein carbonylation is accompanied by diminished complex I activity, impaired respiration, increased superoxide production, and a reduction in membrane potential without changes in mitochondrial number, area, or density. Silencing of the phosphate carrier or NADH dehydrogenase 1α subcomplexes 2 or 3 in 3T3-L1 cells results in decreased basal and maximal respiration. These results suggest that protein carbonylation plays a major instigating role in cytokine-dependent mitochondrial dysfunction and may be linked to the development of insulin resistance in the adipocyte. PMID:22822087

Protein carbonylation and adipocyte mitochondrial function.

Science.gov (United States)

Curtis, Jessica M; Hahn, Wendy S; Stone, Matthew D; Inda, Jacob J; Droullard, David J; Kuzmicic, Jovan P; Donoghue, Margaret A; Long, Eric K; Armien, Anibal G; Lavandero, Sergio; Arriaga, Edgar; Griffin, Timothy J; Bernlohr, David A

2012-09-21

Carbonylation is the covalent, non-reversible modification of the side chains of cysteine, histidine, and lysine residues by lipid peroxidation end products such as 4-hydroxy- and 4-oxononenal. In adipose tissue the effects of such modifications are associated with increased oxidative stress and metabolic dysregulation centered on mitochondrial energy metabolism. To address the role of protein carbonylation in the pathogenesis of mitochondrial dysfunction, quantitative proteomics was employed to identify specific targets of carbonylation in GSTA4-silenced or overexpressing 3T3-L1 adipocytes. GSTA4-silenced adipocytes displayed elevated carbonylation of several key mitochondrial proteins including the phosphate carrier protein, NADH dehydrogenase 1α subcomplexes 2 and 3, translocase of inner mitochondrial membrane 50, and valyl-tRNA synthetase. Elevated protein carbonylation is accompanied by diminished complex I activity, impaired respiration, increased superoxide production, and a reduction in membrane potential without changes in mitochondrial number, area, or density. Silencing of the phosphate carrier or NADH dehydrogenase 1α subcomplexes 2 or 3 in 3T3-L1 cells results in decreased basal and maximal respiration. These results suggest that protein carbonylation plays a major instigating role in cytokine-dependent mitochondrial dysfunction and may be linked to the development of insulin resistance in the adipocyte.

Reviews of recent publications

Directory of Open Access Journals (Sweden)

2005-01-01

Full Text Available Chanan, Michael. Cuban Cinema David William Foster Izenberg, Gerald N. Modernism and Masculinity: Mann, Wedekind, Kandisnky through World War I. Aaron J. Cohen Jonsson, Stefan. Subject Without Nation: Robert Musil and the History of Modern Identity. Post-Contemporary Interventions. Albrecht Classen Kaiser, David Aram. Romanticism, Aesthetics and Nationalism. Cambridge Studies in Romanticism 34. Catherine Grimm Lopez de Martinez, Adelaida and Harriet Turner. The Cambridge Companion to the Spanish Novel: From 1600 to the Present. Toni Dorca McCulloh, Mark R. Understanding W.G. Sebald. Peter C. Pfeiffer Peterson, Dale E. Up From Bondage: The Literatures of Russian and African American Soul. Kathleen M. Ahren

The role of a topologically conserved isoleucine in glutathione transferase structure, stability and function

International Nuclear Information System (INIS)

Achilonu, Ikechukwu; Gildenhuys, Samantha; Fisher, Loren; Burke, Jonathan; Fanucchi, Sylvia; Sewell, B. Trevor; Fernandes, Manuel; Dirr, Heini W.

2010-01-01

The role of a topologically conserved isoleucine in the structure of glutathione transferase was investigated by replacing the Ile71 residue in human GSTA1-1 by alanine or valine. The common fold shared by members of the glutathione-transferase (GST) family has a topologically conserved isoleucine residue at the N-terminus of helix 3 which is involved in the packing of helix 3 against two β-strands in domain 1. The role of the isoleucine residue in the structure, function and stability of GST was investigated by replacing the Ile71 residue in human GSTA1-1 by alanine or valine. The X-ray structures of the I71A and I71V mutants resolved at 1.75 and 2.51 Å, respectively, revealed that the mutations do not alter the overall structure of the protein compared with the wild type. Urea-induced equilibrium unfolding studies using circular dichroism and tryptophan fluorescence suggest that the mutation of Ile71 to alanine or valine reduces the stability of the protein. A functional assay with 1-chloro-2,4-dinitrobenzene shows that the mutation does not significantly alter the function of the protein relative to the wild type. Overall, the results suggest that conservation of the topologically conserved Ile71 maintains the structural stability of the protein but does not play a significant role in catalysis and substrate binding

Sulforaphane induces phase II detoxication enzymes in mouse skin and prevents mutagenesis induced by a mustard gas analog

Energy Technology Data Exchange (ETDEWEB)

Abel, E.L. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States); Boulware, S. [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States); Fields, T.; McIvor, E.; Powell, K.L. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States); DiGiovanni, J.; Vasquez, K.M. [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States); MacLeod, M.C., E-mail: mcmacleod@mdanderson.org [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States)

2013-02-01

Mustard gas, used in chemical warfare since 1917, is a mutagenic and carcinogenic agent that produces severe dermal lesions for which there are no effective therapeutics; it is currently seen as a potential terrorist threat to civilian populations. Sulforaphane, found in cruciferous vegetables, is known to induce enzymes that detoxify compounds such as the sulfur mustards that react through electrophilic intermediates. Here, we observe that a single topical treatment with sulforaphane induces mouse epidermal levels of the regulatory subunit of glutamate-cysteine ligase, the rate-limiting enzyme in glutathione biosynthesis, and also increases epidermal levels of reduced glutathione. Furthermore, a glutathione S-transferase, GSTA4, is also induced in mouse skin by sulforaphane. In an in vivo model in which mice are given a single mutagenic application of the sulfur mustard analog 2-(chloroethyl) ethyl sulfide (CEES), we now show that therapeutic treatment with sulforaphane abolishes the CEES-induced increase in mutation frequency in the skin, measured four days after exposure. Sulforaphane, a natural product currently in clinical trials, shows promise as an effective therapeutic against mustard gas. -- Highlights: ► Sulforaphane induces increased levels of glutathione in mouse skin. ► Sulforaphane induces increased levels of GSTA4 in mouse skin. ► Sulforaphane, applied after CEES-treatment, completely abolishes CEES-mutagenesis. ► The therapeutic effect may suggest a long biological half-life for CEES in vivo.

Population stochastic modelling (PSM)--an R package for mixed-effects models based on stochastic differential equations.

Science.gov (United States)

Klim, Søren; Mortensen, Stig Bousgaard; Kristensen, Niels Rode; Overgaard, Rune Viig; Madsen, Henrik

2009-06-01

The extension from ordinary to stochastic differential equations (SDEs) in pharmacokinetic and pharmacodynamic (PK/PD) modelling is an emerging field and has been motivated in a number of articles [N.R. Kristensen, H. Madsen, S.H. Ingwersen, Using stochastic differential equations for PK/PD model development, J. Pharmacokinet. Pharmacodyn. 32 (February(1)) (2005) 109-141; C.W. Tornøe, R.V. Overgaard, H. Agersø, H.A. Nielsen, H. Madsen, E.N. Jonsson, Stochastic differential equations in NONMEM: implementation, application, and comparison with ordinary differential equations, Pharm. Res. 22 (August(8)) (2005) 1247-1258; R.V. Overgaard, N. Jonsson, C.W. Tornøe, H. Madsen, Non-linear mixed-effects models with stochastic differential equations: implementation of an estimation algorithm, J. Pharmacokinet. Pharmacodyn. 32 (February(1)) (2005) 85-107; U. Picchini, S. Ditlevsen, A. De Gaetano, Maximum likelihood estimation of a time-inhomogeneous stochastic differential model of glucose dynamics, Math. Med. Biol. 25 (June(2)) (2008) 141-155]. PK/PD models are traditionally based ordinary differential equations (ODEs) with an observation link that incorporates noise. This state-space formulation only allows for observation noise and not for system noise. Extending to SDEs allows for a Wiener noise component in the system equations. This additional noise component enables handling of autocorrelated residuals originating from natural variation or systematic model error. Autocorrelated residuals are often partly ignored in PK/PD modelling although violating the hypothesis for many standard statistical tests. This article presents a package for the statistical program R that is able to handle SDEs in a mixed-effects setting. The estimation method implemented is the FOCE(1) approximation to the population likelihood which is generated from the individual likelihoods that are approximated using the Extended Kalman Filter's one-step predictions.

Glutathione S-transferase T1, O1 and O2 polymorphisms are associated with survival in muscle invasive bladder cancer patients.

Directory of Open Access Journals (Sweden)

Tatjana I Djukic

Full Text Available OBJECTIVE: To examine the association of six glutathione transferase (GST gene polymorphisms (GSTT1, GSTP1/rs1695, GSTO1/rs4925, GSTO2/rs156697, GSTM1, GSTA1/rs3957357 with the survival of patients with muscle invasive bladder cancer and the genotype modifying effect on chemotherapy. PATIENTS AND METHODS: A total of 105 patients with muscle invasive bladder cancer were included in the study. The follow-up lasted 5 years. The effect of GSTs polymorphisms on predicting mortality was analyzed by the Cox proportional hazard models, while Kaplan-Meier analysis was performed to assess differences in survival. RESULTS: GSTT1 active, GSTO1 Asp140Asp or GSTO2 Asp142Asp genotypes were independent predictors of a higher risk of death among bladder cancer patients (HR = 2.5, P = 0.028; HR = 2.9, P = 0.022; HR = 3.9, P = 0.001; respectively and significantly influenced the overall survival. There was no association between GSTP1, GSTM1 and GSTA1 gene variants with overall mortality. Only GSTO2 polymorphism showed a significant effect on the survival in the subgroup of patients who received chemotherapy (P = 0.006. CONCLUSION: GSTT1 active genotype and GSTO1 Asp140Asp and GSTO2 Asp142Asp genotypes may have a prognostic/pharmacogenomic role in patients with muscle invasive bladder cancer.

Optical geometry across the horizon

International Nuclear Information System (INIS)

Jonsson, Rickard

2006-01-01

In a recent paper (Jonsson and Westman 2006 Class. Quantum Grav. 23 61), a generalization of optical geometry, assuming a non-shearing reference congruence, is discussed. Here we illustrate that this formalism can be applied to (a finite four-volume) of any spherically symmetric spacetime. In particular we apply the formalism, using a non-static reference congruence, to do optical geometry across the horizon of a static black hole. While the resulting geometry in principle is time dependent, we can choose the reference congruence in such a manner that an embedding of the geometry always looks the same. Relative to the embedded geometry the reference points are then moving. We discuss the motion of photons, inertial forces and gyroscope precession in this framework

Type specimens of centipedes (Myriapoda, Chilopoda in the National Museum, Prague (Czech Republic

Directory of Open Access Journals (Sweden)

Petr Dolejš

2015-06-01

Full Text Available The centipede collection in the National Museum in Prague contains type material of 16 taxa (14 species and two subspecies, of which 15 were described by Luděk J. Dobroruka and one by Karl W. Verhoeff: Allothereua wilsonae Dobroruka, 1979; Chinobius alenae Dobroruka, 1980; Lithobius corrigendus Dobroruka, 1988; L. creticus Dobroruka, 1977; L. erythrocephalus mohelensis Dobroruka, 1959; L. evae Dobroruka, 1958; L. magurensis Dobroruka, 1971; L. purkynei Dobroruka, 1957; L. tatricus Dobroruka, 1958; L. tatricus monounguis Dobroruka, 1958; Monotarsobius homolaci Dobroruka, 1971; M. krali Dobroruka, 1979; Pachymerium dilottiae Dobroruka, 1976; P. hanzaki Dobroruka, 1976; Scolopendra aztecorum Verhoeff, 1934 and Strigamia olympica Dobroruka, 1977. Of these 16 taxa, five were described from the Czech Republic, three from Slovakia and eight from other countries (Greece, Iraq, Kyrgyzstan, Mexico, Nepal, Russia and Uzbekistan. The eight taxa described from the Czech and Slovak Republics are now considered as junior synonyms but the eight taxa described from the other countries are still valid.

Plutonium Chemistry in the UREX+ Separation Processes

Energy Technology Data Exchange (ETDEWEB)

ALena Paulenova; George F. Vandegrift, III; Kenneth R. Czerwinski

2009-10-01

The project "Plutonium Chemistry in the UREX+ Separation Processes” is led by Dr. Alena Paulenova of Oregon State University under collaboration with Dr. George Vandegrift of ANL and Dr. Ken Czerwinski of the University of Nevada at Las Vegas. The objective of the project is to examine the chemical speciation of plutonium in UREX+ (uranium/tributylphosphate) extraction processes for advanced fuel technology. Researchers will analyze the change in speciation using existing thermodynamics and kinetic computer codes to examine the speciation of plutonium in aqueous and organic phases. They will examine the different oxidation states of plutonium to find the relative distribution between the aqueous and organic phases under various conditions such as different concentrations of nitric acid, total nitrates, or actinide ions. They will also utilize techniques such as X-ray absorbance spectroscopy and small-angle neutron scattering for determining plutonium and uranium speciation in all separation stages. The project started in April 2005 and is scheduled for completion in March 2008.

The electronic structure of molecules by a many-body approach. Pt. 1

International Nuclear Information System (INIS)

Niessen, W. von; Cederbaum, L.S.; Kraemer, W.P.

1976-01-01

The ionization potentials of benzene are studied by an ab initio many-body approach which includes the effects of electron correlation and reorganization beyond the one-particle approximation. The calculations confirm the assignment of the photoelectron spectrum experimentally proposed by Jonsson and Lindholm: 1esub(1g)(π), 2esub(2g), 1asub(2u)(π), 2esub(1u), 1bsub(2u), 1bsub(1u), 2asub(1g), 1esub(2g) in order of increasing binding energy. To definitely establish the ordering of the ionization potentials in the second band, which has been very controversial, the corresponding vibrational structure has been calculated. A number of one-electron properties are calculated in the one-particle approximation and compared to experimental work and other theoretical calculations. (orig.) [de

Double scaling limit in O(N) vector models in D dimensions

International Nuclear Information System (INIS)

Di Vecchia, P.; Kato, M.; Ohta, N.

1991-03-01

Using the standard 1/N expansion, we study O(N) vector models in D dimensions with an arbitrary potential. We limit ourselves to renormalizable theories. We show that there exists a value of the coupling constant corresponding to a critical point and that a double scaling limit can be performed as in D=0 and in the case of matrix models in D=0,1. For D=1 the theory is renormalizable with an arbitrary potential and we find in general a hierarchy of critical theories labelled by an integer k. The universal partition function obtained in the double scaling limit is constructed. Finally we show that the critical behaviour of those models is the same as a branched polymer model recently constructed by Ambjoern, Durhuus and Jonsson. (orig.)

Inhibition of liver fibrosis by solubilized coenzyme Q10: Role of Nrf2 activation in inhibiting transforming growth factor-β1 expression

International Nuclear Information System (INIS)

Choi, Hoo-Kyun; Pokharel, Yuba Raj; Lim, Sung Chul; Han, Hyo-Kyung; Ryu, Chang Seon; Kim, Sang Kyum; Kwak, Mi Kyong; Kang, Keon Wook

2009-01-01

Coenzyme Q10 (CoQ10), an endogenous antioxidant, is important in oxidative phosphorylation in mitochondria. It has anti-diabetic and anti-cardiovascular disease effects, but its ability to protect against liver fibrosis has not been studied. Here, we assessed the ability of solubilized CoQ10 to improve dimethylnitrosamine (DMN)-induced liver fibrogenesis in mice. DMN treatments for 3 weeks produced a marked liver fibrosis as assessed by histopathological examination and tissue 4-hydroxyproline content. Solubilized CoQ10 (10 and 30 mg/kg) significantly inhibited both the increases in fibrosis score and 4-hydroxyproline content induced by DMN. Reverse transcription-polymerase chain reaction and Western blot analyses revealed that solubilized CoQ10 inhibited increases in the transforming growth factor-β1 (TGF-β1) mRNA and α-smooth muscle actin (α-SMA) protein by DMN. Interestingly, hepatic glutamate-cysteine ligase (GCL) and glutathione S-transferase A2 (GSTA2) were up-regulated in mice treated with CoQ10. Solubilized CoQ10 also up-regulated antioxidant enzymes such as catalytic subunits of GCL and GSTA2 via activating NF-E2 related factor2 (Nrf2)/antioxidant response element (ARE) in H4IIE hepatoma cells. Moreover, CoQ10's inhibition of α-SMA and TGF-β1 expressions disappeared in Nrf2-null MEF cells. In contrast, Nrf2 overexpression significantly decreased the basal expression levels of α-SMA and TGF-β1 in Nrf2-null MEF cells. These results demonstrated that solubilized CoQ10 inhibited DMN-induced liver fibrosis through suppression of TGF-β1 expression via Nrf2/ARE activation.

Targeting the expression of glutathione- and sulfate-dependent detoxification enzymes in HepG2 cells by oxygen in minimal and amino acid enriched medium.

Science.gov (United States)

Usarek, Ewa; Graboń, Wojciech; Kaźmierczak, Beata; Barańczyk-Kuźma, Anna

2016-02-01

Cancer cells exhibit specific metabolism allowing them to survive and proliferate in various oxygen conditions and nutrients' availability. Hepatocytes are highly active metabolically and thus very sensitive to hypoxia. The purpose of the study was to investigate the effect of oxygen on the expression of phase II detoxification enzymes in hepatocellular carcinoma cells (HepG2) cultured in minimal and rich media (with nonessential amino acids and GSH). The cells were cultured at 1% hypoxia, 10% tissue normoxia, and 21% atmospheric normoxia. The total cell count was determined by trypan blue exclusion dye and the expression on mRNA level by RT-PCR. The result indicated that the expression of glutathione-dependent enzymes (GSTA, M, P, and GPX2) was sensitive to oxygen and medium type. At 1% hypoxia the enzyme expression (with the exception of GSTA) was higher in minimal compared to rich medium, whereas at 10% normoxia it was higher in the rich medium. The expression was oxygen-dependent in both types of medium. Among phenol sulfotransferase SULT1A1 was not sensitive to studied factors, whereas the expression of SULT1A3 was depended on oxygen only in minimal medium. It can be concluded that in HepG2 cells, the detoxification by conjugation with glutathione and, to a lower extent with sulfate, may be affected by hypoxia and/or limited nutrients' availability. Besides, because the data obtained at 10% oxygen significantly differ from those at 21%, the comparative studies on hypoxia should be performed in relation to 10% but not 21% oxygen. Copyright © 2015 Elsevier Inc. All rights reserved.

Population stochastic modelling (PSM)-An R package for mixed-effects models based on stochastic differential equations

DEFF Research Database (Denmark)

Klim, Søren; Mortensen, Stig Bousgaard; Kristensen, Niels Rode

2009-01-01

are often partly ignored in PK/PD modelling although violating the hypothesis for many standard statistical tests. This article presents a package for the statistical program R that is able to handle SDEs in a mixed-effects setting. The estimation method implemented is the FOCE1 approximation......The extension from ordinary to stochastic differential equations (SDEs) in pharmacokinetic and pharmacodynamic (PK/PD) modelling is an emerging field and has been motivated in a number of articles [N.R. Kristensen, H. Madsen, S.H. Ingwersen, Using stochastic differential equations for PK/PD model...... development, J. Pharmacokinet. Pharmacodyn. 32 (February(l)) (2005) 109-141; C.W. Tornoe, R.V Overgaard, H. Agerso, H.A. Nielsen, H. Madsen, E.N. Jonsson, Stochastic differential equations in NONMEM: implementation, application, and comparison with ordinary differential equations, Pharm. Res. 22 (August(8...

Butyrate attenuates lipopolysaccharide-induced inflammation in intestinal cells and Crohn's mucosa through modulation of antioxidant defense machinery.

Directory of Open Access Journals (Sweden)

Ilaria Russo

Full Text Available Oxidative stress plays an important role in the pathogenesis of inflammatory bowel disease (IBD, including Crohn's disease (CrD. High levels of Reactive Oxygen Species (ROS induce the activation of the redox-sensitive nuclear transcription factor kappa-B (NF-κB, which in turn triggers the inflammatory mediators. Butyrate decreases pro-inflammatory cytokine expression by the lamina propria mononuclear cells in CrD patients via inhibition of NF-κB activation, but how it reduces inflammation is still unclear. We suggest that butyrate controls ROS mediated NF-κB activation and thus mucosal inflammation in intestinal epithelial cells and in CrD colonic mucosa by triggering intracellular antioxidant defense systems. Intestinal epithelial Caco-2 cells and colonic mucosa from 14 patients with CrD and 12 controls were challenged with or without lipopolysaccaride from Escherichia coli (EC-LPS in presence or absence of butyrate for 4 and 24 h. The effects of butyrate on oxidative stress, p42/44 MAP kinase phosphorylation, p65-NF-κB activation and mucosal inflammation were investigated by real time PCR, western blot and confocal microscopy. Our results suggest that EC-LPS challenge induces a decrease in Gluthation-S-Transferase-alpha (GSTA1/A2 mRNA levels, protein expression and catalytic activity; enhanced levels of ROS induced by EC-LPS challenge mediates p65-NF-κB activation and inflammatory response in Caco-2 cells and in CrD colonic mucosa. Furthermore butyrate treatment was seen to restore GSTA1/A2 mRNA levels, protein expression and catalytic activity and to control NF-κB activation, COX-2, ICAM-1 and the release of pro-inflammatory cytokine. In conclusion, butyrate rescues the redox machinery and controls the intracellular ROS balance thus switching off EC-LPS induced inflammatory response in intestinal epithelial cells and in CrD colonic mucosa.

Induction of cancer chemopreventive enzymes by coffee is mediated by transcription factor Nrf2. Evidence that the coffee-specific diterpenes cafestol and kahweol confer protection against acrolein

International Nuclear Information System (INIS)

Higgins, Larry G.; Cavin, Christophe; Itoh, Ken; Yamamoto, Masayuki; Hayes, John D.

2008-01-01

Mice fed diets containing 3% or 6% coffee for 5 days had increased levels of mRNA for NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase class Alpha 1 (GSTA1) of between 4- and 20-fold in the liver and small intestine. Mice fed 6% coffee also had increased amounts of mRNA for UDP-glucuronosyl transferase 1A6 (UGT1A6) and the glutamate cysteine ligase catalytic (GCLC) subunit of between 3- and 10-fold in the small intestine. Up-regulation of these mRNAs was significantly greater in mice possessing Nrf2 (NF-E2 p45 subunit-related factor 2) than those lacking the transcription factor. Basal levels of mRNAs for NQO1, GSTA1, UGT1A6 and GCLC were lower in tissues from nrf2 -/- mice than from nrf2 +/+ mice, but modest induction occurred in the mutant animals. Treatment of mouse embryonic fibroblasts (MEFs) from nrf2 +/+ mice with either coffee or the coffee-specific diterpenes cafestol and kahweol (C + K) increased NQO1 mRNA up to 9-fold. MEFs from nrf2 -/- mice expressed less NQO1 mRNA than did wild-type MEFs, but NQO1 was induced modestly by coffee or C + K in the mutant fibroblasts. Transfection of MEFs with nqo1-luciferase reporter constructs showed that induction by C + K was mediated primarily by Nrf2 and required the presence of an antioxidant response element in the 5'-upstream region of the gene. Luciferase reporter activity did not increase following treatment of MEFs with 100 μmol/l furan, suggesting that this ring structure within C + K is insufficient for gene induction. Priming of nrf2 +/+ MEFs, but not nrf2 -/- MEFs, with C + K conferred 2-fold resistance towards acrolein

Torze kolenních extenzorových svalů během izometrických cvičení a ruská elektrická stimulace po zranění kolenních vazů Knee extensor muscles' torque during isometric exercises and russian electrical stimulation following a knee ligament injury

Directory of Open Access Journals (Sweden)

Maciej Płaszewski

2007-02-01

Full Text Available Dobrovolné izometrické cvičení (VOL i neuromuskulární elektrická stimulace (NMES jsou metody rozvoje statické svalové síly. Používají se v programech pro rozvoj síly u zdravých svalů a také pro zotavování svalové funkce za určitých ortopedických podmínek. Obě metody se používají pro zpomalování svalové atrofie a ztráty síly v důsledku imobilizace kolena po zranění (Eriksson & Häggmark, 1979; Ingemann-Hansen & Halkjær-Kristensen, 1985; Johnson, 1988; Wigerstad-Lossing, Tromby, Jonsson, Morelli, Peterson, & Rentröm, 1988. NMES může vyvolat záškuby nebo tetanické svalové kontrakce, a to v závislosti na frekvenci proudových impulsů. Během tetanické stimulace jsou hlavními rysy nácvikových režimů: 1 cyklus zapnutí/vypnutí (pracovní cyklus, tvořený dobou kontrakce a dobou uvolnění; 2 počet kontrakcí; 3 intenzita kontrakcí (dána proudovou amplitudou nebo tolerancí subjektu. Voluntary isometric exercise (VOL and neuromuscular electrical stimulation (NMES are both methods of static muscle strength and girth training. They are applied in strength training programs to healthy muscle as well as for muscle function recovery under certain orthopaedic conditions. Both methods are used to retard muscle atrophy and strength loss resulting from post injury knee immobilization (Eriksson & Häggmark, 1979; Ingemann-Hansen & Halkjær-Kristensen, 1985; Johnson, 1988; Wigerstad-Lossing, Tromby, Jonsson, Morelli, Peterson, & Rentröm, 1988. NMES can elicit twitch or tetanic muscle contractions, determined by current pulse frequency. During tetanic stimulation, the main features of training regimes are: 1 on/off cycle (or duty cycle, made up of the time of contraction plus rest time; 2 the number of contractions; 3 the intensity of contractions (determined by the current amplitude and/or the subject’s tolerance.

CERN Sells its Electronic Document Handling System

CERN Multimedia

2001-01-01

The EDH team. Left to right: Derek Mathieson, Rotislav Titov, Per Gunnar Jonsson, Ivica Dobrovicova, James Purvis. Missing from the photo is Jurgen De Jonghe. In a 1 MCHF deal announced this week, the British company Transacsys bought the rights to CERN's Electronic Document Handling (EDH) system, which has revolutionised the Laboratory's administrative procedures over the last decade. Under the deal, CERN and Transacsys will collaborate on developing EDH over the coming 12 months. CERN will provide manpower and expertise and will retain the rights to use EDH, which will also be available freely to other particle physics laboratories. This development is an excellent example of the active technology transfer policy CERN is currently pursuing. The negotiations were carried out through a fruitful collaboration between AS and ETT Divisions, following the recommendations of the Technology Advisory Board, and with the help of SPL Division. EDH was born in 1991 when John Ferguson and Achille Petrilli of AS Divisi...

Frequency Response Analysis of Hydroelectric Power Plants with Influence From a Non-Linearized Frictional Damping and the Turbine Characteristics

Directory of Open Access Journals (Sweden)

H. Brekke

1985-01-01

Full Text Available The main purpose of the dissertation has been to establish a complete stability analysis of a hydroelectric power plant. The most important part in this study has been to establish a theory for the damping of oscillatory flow in tunnels and pipes. The influence of the turbine characteristics is also important and has been included by differentiation of the turbine equation. The partial derivative values can be found by means of the characteristic diagram of the turbine. Special attention is paid to establishing an empirical friction function for tunnels with rough walls. The author has based his theory on experimental tests carried out for damping of sea waves on rough beds, and the friction factor is a function of both frequency, amplitudes, cross section area and roughness of the wall (Jonsson 1978. Further, the damping of oscillations in shafts leading to tunnels taking into account the mean velocity in the tunnel has been established.

Evaluation of INL Supplied MOOSE/OSPREY Model: Modeling Water Adsorption on Type 3A Molecular Sieve

Energy Technology Data Exchange (ETDEWEB)

Pompilio, L. M. [Syracuse University; DePaoli, D. W. [ORNL; Spencer, B. B. [ORNL

2014-08-29

The purpose of this study was to evaluate Idaho National Lab’s Multiphysics Object-Oriented Simulation Environment (MOOSE) software in modeling the adsorption of water onto type 3A molecular sieve (3AMS). MOOSE can be thought-of as a computing framework within which applications modeling specific coupled-phenomena can be developed and run. The application titled Off-gas SeParation and REcoverY (OSPREY) has been developed to model gas sorption in packed columns. The sorbate breakthrough curve calculated by MOOSE/OSPREY was compared to results previously obtained in the deep bed hydration tests conducted at Oak Ridge National Laboratory. The coding framework permits selection of various options, when they exist, for modeling a process. For example, the OSPREY module includes options to model the adsorption equilibrium with a Langmuir model or a generalized statistical thermodynamic adsorption (GSTA) model. The vapor solid equilibria and the operating conditions of the process (e.g., gas phase concentration) are required to calculate the concentration gradient driving the mass transfer between phases. Both the Langmuir and GSTA models were tested in this evaluation. Input variables were either known from experimental conditions, or were available (e.g., density) or were estimated (e.g., thermal conductivity of sorbent) from the literature. Variables were considered independent of time, i.e., rather than having a mass transfer coefficient that varied with time or position in the bed, the parameter was set to remain constant. The calculated results did not coincide with data from laboratory tests. The model accurately estimated the number of bed volumes processed for the given operating parameters, but breakthrough times were not accurately predicted, varying 50% or more from the data. The shape of the breakthrough curves also differed from the experimental data, indicating a much wider sorption band. Model modifications are needed to improve its utility and

Factors Affecting the Adoption of Gamified Smart Tourism Applications: An Integrative Approach

Directory of Open Access Journals (Sweden)

Changsok Yoo

2017-11-01

Full Text Available Considering that the core concerns in sustainability are threats to the survival of humankind and the ecosystems that humans depend on, changing the consumption and production behaviors of individuals and society is inevitable. However, people are reluctant to change their own behavior in support of sustainability goals. This tendency seems to be especially strong in tourism because the main value of tourism is hedonic utility. Thus, the tourism industry is now introducing gamification and smart tourism to shift tourist behavior toward sustainability, but most of studies and practices only focus on the performance and application of gamification without considering customer adoption patterns and perceptions during the process. This study empirically investigated what factors affect the adoption of smart tourism applications that incorporate game elements, using the Google Maps tourist guide program. As an initial approach, we incorporated diverse theoretical approaches: perceived usefulness; perceived ease of use; perceived enjoyment from technology acceptance model; information and interaction motivations from the uses and gratifications theory; the network effect; distributive justice; flow as responses to the game characteristics of smart tourism applications; and information privacy concerns as a negative factor for diffusion. The result showed that hedonic characteristics of the gamified smart tourism application (GSTA are strong in adoption. Perceived enjoyment had a significant influence on the intention to use, but information quality, related to cognitive experience, did not. The flow and perceived distributive justice associated with the game content were not significant, but the interaction motivation was significant in the research model. The results of this study show that individuals regard a GSTA as a low-level game tool. Also, it is important to preoccupy the smart tourism application market in terms of marketing strategy because

Antioxidant role of glutathione S-transferases: 4-Hydroxynonenal, a key molecule in stress-mediated signaling.

Science.gov (United States)

Singhal, Sharad S; Singh, Sharda P; Singhal, Preeti; Horne, David; Singhal, Jyotsana; Awasthi, Sanjay

2015-12-15

4-Hydroxy-2-trans-nonenal (4HNE), one of the major end products of lipid peroxidation (LPO), has been shown to induce apoptosis in a variety of cell lines. It appears to modulate signaling processes in more than one way because it has been suggested to have a role in signaling for differentiation and proliferation. It has been known that glutathione S-transferases (GSTs) can reduce lipid hydroperoxides through their Se-independent glutathione-peroxidase activity and that these enzymes can also detoxify LPO end-products such as 4HNE. Available evidence from earlier studies together with results of recent studies in our laboratories strongly suggests that LPO products, particularly hydroperoxides and 4HNE, are involved in the mechanisms of stress-mediated signaling and that it can be modulated by the alpha-class GSTs through the regulation of the intracellular concentrations of 4HNE. We demonstrate that 4HNE induced apoptosis in various cell lines is accompanied with c-Jun-N-terminal kinase (JNK) and caspase-3 activation. Cells exposed to mild, transient heat or oxidative stress acquire the capacity to exclude intracellular 4HNE at a faster rate by inducing GSTA4-4 which conjugates 4HNE to glutathione (GSH), and RLIP76 which mediates the ATP-dependent transport of the GSH-conjugate of 4HNE (GS-HNE). The balance between formation and exclusion promotes different cellular processes - higher concentrations of 4HNE promote apoptosis; whereas, lower concentrations promote proliferation. In this article, we provide a brief summary of the cellular effects of 4HNE, followed by a review of its GST-catalyzed detoxification, with an emphasis on the structural attributes that play an important role in the interactions with alpha-class GSTA4-4. Taken together, 4HNE is a key signaling molecule and that GSTs being determinants of its intracellular concentrations, can regulate stress-mediated signaling, are reviewed in this article. Copyright © 2015 Elsevier Inc. All rights

Dissociation of water and Acetic acid on PbS from first principles

Science.gov (United States)

Satta, Alessandra; Ruggerone, Paolo; de Giudici, Giovanni

2008-03-01

The adsorption of complex molecules at mineral surfaces are crucial ingredients for understanding the mechanisms that rule the interaction between minerals and the biosphere and for predicting both the stability and the reactivity of minerals. The present work focuses mainly on the early stages of different adsorption reactions occurring at both the cleavage surface and a high-index vicinal surface of galena (PbS). We have studied the dissociation mechanism of water and acetic acid on the galena surfaces by means of ab initio calculations within the framework of the density functional theory in the generalized gradient approximation and of pseudopotential approach. The calculated adsorption energies of the molecules indicate the stepped surface as the most reactive, as expected. The free energy surface during the reaction process has been explored via metadynamics[1]. The optimized configurations of both reactants and products obtained, were then used to accurately calculate the dissociation energy via the Nudge Elastic Band method[2]. [1] A. Laio and M. Parrinello, PNAS 99, 12562 (2002). [2] G. Mills and H. Jonsson, Phys. Rev. Lett. 72, 1124 (1994).

An improved financial tool to replace BHT

CERN Multimedia

2002-01-01

In November, the BHT tool used to control financial data will be replaced by an improved and more powerful system, called CET for CERN Expenditure Tracking. The team in charge of CET. From left to right, sitting, Martyn Rankin, David McGlashan, standing, Per Gunnar Jonsson, James Purvis and Mikael Angberg. After 10 years of BHT at CERN, in order to face the challenges of the LHC era, and following the recommendations of the External Review Committee, the BHT application will be replaced by an improved and more powerful expenditure tracking tool called CET for CERN Expenditure Tracking. For those who are not familiar with it, the BHT, Budget Holders Toolkit, is a utility that provides a way to view CERN financial data. It is available for users who have access to at least one budget code. The new CET represents a tool that not only allows powerful analysis of the past, but also assists in forecasting the future. CET will offer significantly more functionality than BHT, including extended contract analysis, ...

Sorption Modeling and Verification for Off-Gas Treatment

Energy Technology Data Exchange (ETDEWEB)

Tavlarides, Lawrence L. [Syracuse Univ., NY (United States); Lin, Ronghong [Syracuse Univ., NY (United States); Nan, Yue [Syracuse Univ., NY (United States); Yiacoumi, Sotira [Georgia Inst. of Technology, Atlanta, GA (United States); Tsouris, Costas [Georgia Inst. of Technology, Atlanta, GA (United States); Ladshaw, Austin [Georgia Inst. of Technology, Atlanta, GA (United States); Sharma, Ketki [Georgia Inst. of Technology, Atlanta, GA (United States); Gabitto, Jorge [Prairie View A & M Univ., Prairie View, TX (United States); DePaoli, David [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2015-04-29

The project has made progress toward developing a comprehensive modeling capability for the capture of target species in off gas evolved during the reprocessing of nuclear fuel. The effort has integrated experimentation, model development, and computer code development for adsorption and absorption processes. For adsorption, a modeling library has been initiated to include (a) equilibrium models for uptake of off-gas components by adsorbents, (b) mass transfer models to describe mass transfer to a particle, diffusion through the pores of the particle and adsorption on the active sites of the particle, and (c) interconnection of these models to fixed bed adsorption modeling which includes advection through the bed. For single-component equilibria, a Generalized Statistical Thermodynamic Adsorption (GSTA) code was developed to represent experimental data from a broad range of isotherm types; this is equivalent to a Langmuir isotherm in the two-parameter case, and was demonstrated for Kr on INL-engineered sorbent HZ PAN, water sorption on molecular sieve A sorbent material (MS3A), and Kr and Xe capture on metal-organic framework (MOF) materials. The GSTA isotherm was extended to multicomponent systems through application of a modified spreading pressure surface activity model and generalized predictive adsorbed solution theory; the result is the capability to estimate multicomponent adsorption equilibria from single-component isotherms. This advance, which enhances the capability to simulate systems related to off-gas treatment, has been demonstrated for a range of real-gas systems in the literature and is ready for testing with data currently being collected for multicomponent systems of interest, including iodine and water on MS3A. A diffusion kinetic model for sorbent pellets involving pore and surface diffusion as well as external mass transfer has been established, and a methodology was developed for determining unknown diffusivity parameters from transient

Sorption Modeling and Verification for Off-Gas Treatment

International Nuclear Information System (INIS)

Tavlarides, Lawrence L.; Lin, Ronghong; Nan, Yue; Yiacoumi, Sotira; Tsouris, Costas; Ladshaw, Austin; Sharma, Ketki; Gabitto, Jorge; DePaoli, David

2015-01-01

The project has made progress toward developing a comprehensive modeling capability for the capture of target species in off gas evolved during the reprocessing of nuclear fuel. The effort has integrated experimentation, model development, and computer code development for adsorption and absorption processes. For adsorption, a modeling library has been initiated to include (a) equilibrium models for uptake of off-gas components by adsorbents, (b) mass transfer models to describe mass transfer to a particle, diffusion through the pores of the particle and adsorption on the active sites of the particle, and (c) interconnection of these models to fixed bed adsorption modeling which includes advection through the bed. For single-component equilibria, a Generalized Statistical Thermodynamic Adsorption (GSTA) code was developed to represent experimental data from a broad range of isotherm types; this is equivalent to a Langmuir isotherm in the two-parameter case, and was demonstrated for Kr on INL-engineered sorbent HZ PAN, water sorption on molecular sieve A sorbent material (MS3A), and Kr and Xe capture on metal-organic framework (MOF) materials. The GSTA isotherm was extended to multicomponent systems through application of a modified spreading pressure surface activity model and generalized predictive adsorbed solution theory; the result is the capability to estimate multicomponent adsorption equilibria from single-component isotherms. This advance, which enhances the capability to simulate systems related to off-gas treatment, has been demonstrated for a range of real-gas systems in the literature and is ready for testing with data currently being collected for multicomponent systems of interest, including iodine and water on MS3A. A diffusion kinetic model for sorbent pellets involving pore and surface diffusion as well as external mass transfer has been established, and a methodology was developed for determining unknown diffusivity parameters from transient

Comparative gene expression of intestinal metabolizing enzymes.

Science.gov (United States)

Shin, Ho-Chul; Kim, Hye-Ryoung; Cho, Hee-Jung; Yi, Hee; Cho, Soo-Min; Lee, Dong-Goo; Abd El-Aty, A M; Kim, Jin-Suk; Sun, Duxin; Amidon, Gordon L

2009-11-01

The purpose of this study was to compare the expression profiles of drug-metabolizing enzymes in the intestine of mouse, rat and human. Total RNA was isolated from the duodenum and the mRNA expression was measured using Affymetrix GeneChip oligonucleotide arrays. Detected genes from the intestine of mouse, rat and human were ca. 60% of 22690 sequences, 40% of 8739 and 47% of 12559, respectively. Total genes of metabolizing enzymes subjected in this study were 95, 33 and 68 genes in mouse, rat and human, respectively. Of phase I enzymes, the mouse exhibited abundant gene expressions for Cyp3a25, Cyp4v3, Cyp2d26, followed by Cyp2b20, Cyp2c65 and Cyp4f14, whereas, the rat showed higher expression profiles of Cyp3a9, Cyp2b19, Cyp4f1, Cyp17a1, Cyp2d18, Cyp27a1 and Cyp4f6. However, the highly expressed P450 enzymes were CYP3A4, CYP3A5, CYP4F3, CYP2C18, CYP2C9, CYP2D6, CYP3A7, CYP11B1 and CYP2B6 in the human. For phase II enzymes, glucuronosyltransferase Ugt1a6, glutathione S-transferases Gstp1, Gstm3 and Gsta2, sulfotransferase Sult1b1 and acyltransferase Dgat1 were highly expressed in the mouse. The rat revealed predominant expression of glucuronosyltransferases Ugt1a1 and Ugt1a7, sulfotransferase Sult1b1, acetyltransferase Dlat and acyltransferase Dgat1. On the other hand, in human, glucuronosyltransferases UGT2B15 and UGT2B17, glutathione S-transferases MGST3, GSTP1, GSTA2 and GSTM4, sulfotransferases ST1A3 and SULT1A2, acetyltransferases SAT1 and CRAT, and acyltransferase AGPAT2 were dominantly detected. Therefore, current data indicated substantial interspecies differences in the pattern of intestinal gene expression both for P450 enzymes and phase II drug-metabolizing enzymes. This genomic database is expected to improve our understanding of interspecies variations in estimating intestinal prehepatic clearance of oral drugs.

Modulation of keratinocyte expression of antioxidants by 4-hydroxynonenal, a lipid peroxidation end product

Energy Technology Data Exchange (ETDEWEB)

Zheng, Ruijin [Pharmacology and Toxicology and Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ (United States); Heck, Diane E. [Environmental Health Science, New York Medical College, Valhalla, NY (United States); Mishin, Vladimir; Black, Adrienne T. [Pharmacology and Toxicology and Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ (United States); Shakarjian, Michael P. [Environmental Health Science, New York Medical College, Valhalla, NY (United States); Kong, Ah-Ng Tony; Laskin, Debra L. [Pharmacology and Toxicology and Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ (United States); Laskin, Jeffrey D., E-mail: jlaskin@eohsi.rutgers.edu [Environmental and Occupational Medicine, Rutgers University-Robert Wood Johnson Medical School, Piscataway, NJ (United States)

2014-03-01

4-Hydroxynonenal (4-HNE) is a lipid peroxidation end product generated in response to oxidative stress in the skin. Keratinocytes contain an array of antioxidant enzymes which protect against oxidative stress. In these studies, we characterized 4-HNE-induced changes in antioxidant expression in mouse keratinocytes. Treatment of primary mouse keratinocytes and PAM 212 keratinocytes with 4-HNE increased mRNA expression for heme oxygenase-1 (HO-1), catalase, NADPH:quinone oxidoreductase (NQO1) and glutathione S-transferase (GST) A1-2, GSTA3 and GSTA4. In both cell types, HO-1 was the most sensitive, increasing 86–98 fold within 6 h. Further characterization of the effects of 4-HNE on HO-1 demonstrated concentration- and time-dependent increases in mRNA and protein expression which were maximum after 6 h with 30 μM. 4-HNE stimulated keratinocyte Erk1/2, JNK and p38 MAP kinases, as well as PI3 kinase. Inhibition of these enzymes suppressed 4-HNE-induced HO-1 mRNA and protein expression. 4-HNE also activated Nrf2 by inducing its translocation to the nucleus. 4-HNE was markedly less effective in inducing HO-1 mRNA and protein in keratinocytes from Nrf2 −/− mice, when compared to wild type mice, indicating that Nrf2 also regulates 4-HNE-induced signaling. Western blot analysis of caveolar membrane fractions isolated by sucrose density centrifugation demonstrated that 4-HNE-induced HO-1 is localized in keratinocyte caveolae. Treatment of the cells with methyl-β-cyclodextrin, which disrupts caveolar structure, suppressed 4-HNE-induced HO-1. These findings indicate that 4-HNE modulates expression of antioxidant enzymes in keratinocytes, and that this can occur by different mechanisms. Changes in expression of keratinocyte antioxidants may be important in protecting the skin from oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a reactive aldehyde. • 4-HNE induces antioxidant proteins in mouse keratinocytes. • Induction of

Differential gene expression profiling of endometrium during the mid-luteal phase of the estrous cycle between a repeat breeder (RB) and non-RB cows.

Science.gov (United States)

Hayashi, Ken-Go; Hosoe, Misa; Kizaki, Keiichiro; Fujii, Shiori; Kanahara, Hiroko; Takahashi, Toru; Sakumoto, Ryosuke

2017-03-23

Repeat breeding directly affects reproductive efficiency in cattle due to an increase in services per conception and calving interval. This study aimed to investigate whether changes in endometrial gene expression profile are involved in repeat breeding in cows. Differential gene expression profiles of the endometrium were investigated during the mid-luteal phase of the estrous cycle between repeat breeder (RB) and non-RB cows using microarray analysis. The caruncular (CAR) and intercaruncular (ICAR) endometrium of both ipsilateral and contralateral uterine horns to the corpus luteum were collected from RB (inseminated at least three times but not pregnant) and non-RB cows on Day 15 of the estrous cycle (4 cows/group). Global gene expression profiles of these endometrial samples were analyzed with a 15 K custom-made oligo-microarray for cattle. Immunohistochemistry was performed to investigate the cellular localization of proteins of three identified transcripts in the endometrium. Microarray analysis revealed that 405 and 397 genes were differentially expressed in the CAR and ICAR of the ipsilateral uterine horn of RB, respectively when compared with non-RB cows. In the contralateral uterine horn, 443 and 257 differentially expressed genes were identified in the CAR and ICAR of RB, respectively when compared with non-RB cows. Gene ontology analysis revealed that genes involved in development and morphogenesis were mainly up-regulated in the CAR of RB cows. In the ICAR of both the ipsilateral and contralateral uterine horns, genes related to the metabolic process were predominantly enriched in the RB cows when compared with non-RB cows. In the analysis of the whole uterus (combining the data above four endometrial compartments), RB cows showed up-regulation of 37 genes including PRSS2, GSTA3 and PIPOX and down-regulation of 39 genes including CHGA, KRT35 and THBS4 when compared with non-RB cows. Immunohistochemistry revealed that CHGA, GSTA3 and PRSS2 proteins

Naturally occurring genetic variability in expression of Gsta4 is associated with differential survival of axotomized rat motoneurons

DEFF Research Database (Denmark)

Mikael, Ström; Al Nimer, Faiez; Lindblom, Rickard

2012-01-01

A large number of molecular pathways have been implicated in the degeneration of axotomized motoneurons. We previously have demonstrated substantial differences in the survival rate of axotomized motoneurons across different rat strains. Identification of genetic differences underlying such natur...

Curcumin inhibits development and cell adhesion in Dictyostelium discoideum: Implications for YakA signaling and GST enzyme function

Energy Technology Data Exchange (ETDEWEB)

Garige, Mamatha; Walters, Eric, E-mail: ewalters@howard.edu

2015-11-13

The molecular basis for nutraceutical properties of the polyphenol curcumin (Curcuma longa, Turmeric) is complex, affecting multiple factors that regulate cell signaling and homeostasis. Here, we report the effect of curcumin on cellular and developmental mechanisms in the eukaryotic model, Dictyostelium discoideum. Dictyostelium proliferation was inhibited in the presence of curcumin, which also suppressed the prestarvation marker, discoidin I, members of the yakA-mediated developmental signaling pathway, and expression of the extracellular matrix/cell adhesion proteins (DdCAD and csA). This resulted in delayed chemotaxis, adhesion, and development of the organism. In contrast to the inhibitory effects on developmental genes, curcumin induced gstA gene expression, overall GST activity, and generated production of reactive oxygen species. These studies expand our knowledge of developmental and biochemical signaling influenced by curcumin, and lends greater consideration of GST enzyme function in eukaryotic cell signaling, development, and differentiation.

Curcumin inhibits development and cell adhesion in Dictyostelium discoideum: Implications for YakA signaling and GST enzyme function

International Nuclear Information System (INIS)

Garige, Mamatha; Walters, Eric

2015-01-01

The molecular basis for nutraceutical properties of the polyphenol curcumin (Curcuma longa, Turmeric) is complex, affecting multiple factors that regulate cell signaling and homeostasis. Here, we report the effect of curcumin on cellular and developmental mechanisms in the eukaryotic model, Dictyostelium discoideum. Dictyostelium proliferation was inhibited in the presence of curcumin, which also suppressed the prestarvation marker, discoidin I, members of the yakA-mediated developmental signaling pathway, and expression of the extracellular matrix/cell adhesion proteins (DdCAD and csA). This resulted in delayed chemotaxis, adhesion, and development of the organism. In contrast to the inhibitory effects on developmental genes, curcumin induced gstA gene expression, overall GST activity, and generated production of reactive oxygen species. These studies expand our knowledge of developmental and biochemical signaling influenced by curcumin, and lends greater consideration of GST enzyme function in eukaryotic cell signaling, development, and differentiation.

Research document no. 20. The constitutionalizing of the international legal regime of the petroleum investments and the world market reconstruction

International Nuclear Information System (INIS)

Noel, P.

2000-09-01

We analyse the new international legal regime for upstream petroleum investments and ''state contracts'' in general. In striking contrast to the ''New international economic order'' and ''Permanent sovereignty over natural resources'' ideologies of the 1960 and 1970, the emerging regime promotes the sanctification of contractual economic rights; the strict definition of State sovereign prerogatives, and the severe limitation of their conditions of exercise; the internationalization of the settlement of disputes through direct firm-State arbitration; the integration of national territories in a competitive, transparent, non-discriminative global market for investment. We demonstrate that it is rooted in the principles of liberal constitutionalism, hence promoting the internationalization of the Rule of Law. Such a legal regime is conducive to the expansion of the market for petroleum rights, as it restores the institutional conditions for credible commitment by the State. It will also accelerate the trend toward the ''commoditization'' of hydrocarbon resources. Bilateral investments treaties (especially the United States BIT program) as well as multilateral/regional instruments both general (draft MAI, MIGA, MERCOSUR, ALENA) and energy-specific (Energy Charter Treaty) are analysed as the main pillars and diffusion mechanisms of the new regime. A final paragraph indicates the way forward: the evaluation of the impact of this new legal regime on the world oil supply curve, especially as it eventually reaches - or not - some of the lowest-cost, biggest-resources countries. (author)

Scale-dependency of the global mean surface temperature trend and its implication for the recent hiatus of global warming.

Science.gov (United States)

Lin, Yong; Franzke, Christian L E

2015-08-11

Studies of the global mean surface temperature trend are typically conducted at a single (usually annual or decadal) time scale. The used scale does not necessarily correspond to the intrinsic scales of the natural temperature variability. This scale mismatch complicates the separation of externally forced temperature trends from natural temperature fluctuations. The hiatus of global warming since 1999 has been claimed to show that human activities play only a minor role in global warming. Most likely this claim is wrong due to the inadequate consideration of the scale-dependency in the global surface temperature (GST) evolution. Here we show that the variability and trend of the global mean surface temperature anomalies (GSTA) from January 1850 to December 2013, which incorporate both land and sea surface data, is scale-dependent and that the recent hiatus of global warming is mainly related to natural long-term oscillations. These results provide a possible explanation of the recent hiatus of global warming and suggest that the hiatus is only temporary.

Association of 5' end neuregulin-1 (NRG1) gene variation with subcortical medial frontal microstructure in humans.

Science.gov (United States)

Winterer, Georg; Konrad, Andreas; Vucurevic, Goran; Musso, Francesco; Stoeter, Peter; Dahmen, Norbert

2008-04-01

Animal data suggest that the gene neuregulin-1 (NRG1) is involved in neuronal myelination. A haplotype (deCODE) in the 5' end region of the gene was described to double the risk for schizophrenia in an Icelandic population (Stefansson, H., Sigurdsson, E., Steinthorsdottir, V., Bjornsdottir, S., Sigmundsson, T., Ghosh, S., Brynjolfsson, J., Gunnarsdottir, S., Ivarsson, O., Chou, T.T., Hjaltason, O., Birgisdottir, B., Jonsson, H., Gudnadottir, V.G., Gudmundsdottir, E., Bjornsson, A., Ingvarsson, B., Ingason, A., Sigfusson, S., Hardardottir, H., Harvey, R.P., Lai, D., Zhou, M., Brunner, D., Mutel, V., Gonzalo, A., Lemke, G., Sainz, J., Johannesson, G., Andresson, T., Gudbjartsson, D., Manolescu, A., Frigge, M.L., Gurney, M.E., Kong, A., Gulcher, J.R., Petursson, H., Stefansson, K. 2002. Neuregulin-1 and susceptibility to schizophrenia. Am. J. Hum. Genet. 71, 877-892). Of note, there is now increasing evidence of disturbed myelination in this illness--particularly in subcortical frontal lobe white matter (Konrad, A., Winterer, G. 2008. Disturbed structural connectivity in schizophrenia--primary factor in pathology or epiphenomenon? Schiz. Bull. [Electronic publication ahead of print]). Therefore, we investigated with diffusion tensor imaging (DTI) the impact of a tagging single nucleotide polymorphism (SNP) from the deCODE haplotype, i.e., SNP8NRG221533, on fractional anisotropy (FA), which reflects structural integrity of white matter. SNP8NRG221533 was selected because it gave the single best uncorrected association with schizophrenia in the original report by Stefansson et al. (Stefansson, H., Sigurdsson, E., Steinthorsdottir, V., Bjornsdottir, S., Sigmundsson, T., Ghosh, S., Brynjolfsson, J., Gunnarsdottir, S., Ivarsson, O., Chou, T.T., Hjaltason, O., Birgisdottir, B., Jonsson, H., Gudnadottir, V.G., Gudmundsdottir, E., Bjornsson, A., Ingvarsson, B., Ingason, A., Sigfusson, S., Hardardottir, H., Harvey, R.P., Lai, D., Zhou, M., Brunner, D., Mutel, V., Gonzalo, A

Nrf2 protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced oxidative injury and steatohepatitis

International Nuclear Information System (INIS)

Lu Hong; Cui Wei; Klaassen, Curtis D.

2011-01-01

Previous studies demonstrate that Nrf2, a master regulator of antioxidative responses, is essential in mediating induction of many antioxidative enzymes by acute activation of the AhR. However, the role of Nrf2 in protecting against oxidative stress and DNA damage induced by sustained activation of the AhR remains unknown and was investigated herein. Tissue and blood samples were collected from wild-type (WT) and Nrf2-null mice 21 days after administration of a low-toxic dose (10 μg/kg ip) of TCDD. Only Nrf2-null mice lost body weight after TCDD treatment; however, blood levels of ALT were not markedly changed in either genotype, indicating a lack of extensive necrosis. Compared to livers of TCDD-treated WT mice, livers of TCDD-treated Nrf2-null mice had: 1) degenerated hepatocytes, lobular inflammation, marked fat accumulation, and higher mRNA expression of inflammatory and fibrotic genes; 2) depletion of glutathione, elevation in lipid peroxidation and marker of DNA damage; 3) attenuated induction of phase-II enzymes Nqo1, Gsta1/2, and Ugt2b35 mRNAs, but higher induction of cytoprotective Ho-1, Prdx1, Trxr1, Gclc, and Epxh1 mRNAs; 4) higher mRNA expression of Fgf21 and triglyceride-synthesis genes, but down-regulation of bile-acid-synthesis genes and cholesterol-efflux transporters; and 5) trend of induction/activation of c-jun and NF-kB. Additionally, TCDD-treated Nrf2-null mice had impaired adipogenesis in white adipose tissue. In conclusion, Nrf2 protects livers of mice against oxidative stress, DNA damage, and steatohepatitis induced by TCDD-mediated sustained activation of the AhR. The aggravated hepatosteatosis in TCDD-treated Nrf2-null mice is due to increased lipogenesis in liver and impaired lipogenesis in white adipose tissue. - Highlights: → TCDD causes hepatosteatosis and induction of Nrf2-target genes in wild-type mice. → TCDD causes weight loss, oxidative injury, and steatohepatitis in Nrf2-null mice. → Livers of TCDD-treated Nrf2-null mice

Antioxidant role of glutathione S-transferases: 4-Hydroxynonenal, a key molecule in stress-mediated signaling

International Nuclear Information System (INIS)

Singhal, Sharad S.; Singh, Sharda P.; Singhal, Preeti; Horne, David; Singhal, Jyotsana; Awasthi, Sanjay

2015-01-01

4-Hydroxy-2-trans-nonenal (4HNE), one of the major end products of lipid peroxidation (LPO), has been shown to induce apoptosis in a variety of cell lines. It appears to modulate signaling processes in more than one way because it has been suggested to have a role in signaling for differentiation and proliferation. It has been known that glutathione S-transferases (GSTs) can reduce lipid hydroperoxides through their Se-independent glutathione-peroxidase activity and that these enzymes can also detoxify LPO end-products such as 4HNE. Available evidence from earlier studies together with results of recent studies in our laboratories strongly suggests that LPO products, particularly hydroperoxides and 4HNE, are involved in the mechanisms of stress-mediated signaling and that it can be modulated by the alpha-class GSTs through the regulation of the intracellular concentrations of 4HNE. We demonstrate that 4HNE induced apoptosis in various cell lines is accompanied with c-Jun-N-terminal kinase (JNK) and caspase-3 activation. Cells exposed to mild, transient heat or oxidative stress acquire the capacity to exclude intracellular 4HNE at a faster rate by inducing GSTA4-4 which conjugates 4HNE to glutathione (GSH), and RLIP76 which mediates the ATP-dependent transport of the GSH-conjugate of 4HNE (GS-HNE). The balance between formation and exclusion promotes different cellular processes — higher concentrations of 4HNE promote apoptosis; whereas, lower concentrations promote proliferation. In this article, we provide a brief summary of the cellular effects of 4HNE, followed by a review of its GST-catalyzed detoxification, with an emphasis on the structural attributes that play an important role in the interactions with alpha-class GSTA4-4. Taken together, 4HNE is a key signaling molecule and that GSTs being determinants of its intracellular concentrations, can regulate stress-mediated signaling, are reviewed in this article. - Highlights: • GSTs are the major

Research document no. 20. The constitutionalizing of the international legal regime of the petroleum investments and the world market reconstruction; Cahier de recherche no. 20. La constitutionalisation du regime juridique international des investissements petroliers et la (re)construction du marche mondial

Energy Technology Data Exchange (ETDEWEB)

Noel, P

2000-09-01

We analyse the new international legal regime for upstream petroleum investments and ''state contracts'' in general. In striking contrast to the ''New international economic order'' and ''Permanent sovereignty over natural resources'' ideologies of the 1960 and 1970, the emerging regime promotes the sanctification of contractual economic rights; the strict definition of State sovereign prerogatives, and the severe limitation of their conditions of exercise; the internationalization of the settlement of disputes through direct firm-State arbitration; the integration of national territories in a competitive, transparent, non-discriminative global market for investment. We demonstrate that it is rooted in the principles of liberal constitutionalism, hence promoting the internationalization of the Rule of Law. Such a legal regime is conducive to the expansion of the market for petroleum rights, as it restores the institutional conditions for credible commitment by the State. It will also accelerate the trend toward the ''commoditization'' of hydrocarbon resources. Bilateral investments treaties (especially the United States BIT program) as well as multilateral/regional instruments both general (draft MAI, MIGA, MERCOSUR, ALENA) and energy-specific (Energy Charter Treaty) are analysed as the main pillars and diffusion mechanisms of the new regime. A final paragraph indicates the way forward: the evaluation of the impact of this new legal regime on the world oil supply curve, especially as it eventually reaches - or not - some of the lowest-cost, biggest-resources countries. (author)

Análisis observacional de la construcción de las secuencias ofensivas que acaban en lanzamiento en baloncesto de categoría infantil

Directory of Open Access Journals (Sweden)

Daniel Lapresa Ajamil

2014-01-01

Full Text Available El presente trabajo analiza la construcción de las secuencias ofensivas que acaban en lanzamiento de uno de los mejores equipos españoles de baloncesto en categoría infantil (Real Madrid. A partir de los datos obtenidos mediante el instrumento de observación SOBL-2, elaborado ad hoc por Fernández, Camerino, Anguera y Jonsson (2009, se ha realizado un análisis estadístico descriptivo e inferencial –mediante el programa SPSS, versión 19.0– y otro en busca de patrones temporales –mediante el software Theme, versión 5.0–, que nos han permitido caracterizar la construcción de las secuencias ofensivas –eficaces e ineficaces– que acaban en lanzamiento. Además, la comparación de estas secuencias con las propias del baloncesto de élite ha evidenciado las dificultades y/o limitaciones que posee el jugador de baloncesto de esta edad bajo las actuales premisas de juego correspondientes a la categoría infantil. Los resultados sugieren la conveniencia de adaptar el juego de baloncesto en categoría infantil a partir de la manifiesta dificultad que encuentran los jugadores para mostrarse competentes en lanzamientos exteriores.

Scale-dependency of the global mean surface temperature trend and its implication for the recent hiatus of global warming

Science.gov (United States)

Lin, Yong; Franzke, Christian L. E.

2015-01-01

Studies of the global mean surface temperature trend are typically conducted at a single (usually annual or decadal) time scale. The used scale does not necessarily correspond to the intrinsic scales of the natural temperature variability. This scale mismatch complicates the separation of externally forced temperature trends from natural temperature fluctuations. The hiatus of global warming since 1999 has been claimed to show that human activities play only a minor role in global warming. Most likely this claim is wrong due to the inadequate consideration of the scale-dependency in the global surface temperature (GST) evolution. Here we show that the variability and trend of the global mean surface temperature anomalies (GSTA) from January 1850 to December 2013, which incorporate both land and sea surface data, is scale-dependent and that the recent hiatus of global warming is mainly related to natural long-term oscillations. These results provide a possible explanation of the recent hiatus of global warming and suggest that the hiatus is only temporary. PMID:26259555

The Role of Genotypes That Modify the Toxicity of Chemical Mutagens in the Risk for Myeloproliferative Neoplasms

Directory of Open Access Journals (Sweden)

Carol Ann Gross-Davis

2015-02-01

Full Text Available Background: The etiology of myeloproliferative neoplasms (MPN (polycythemia vera; essential thrombocythemia; primary myelofibrosis is unknown, however they are associated with a somatic mutation—JAK2 V617F—suggesting a potential role for environmental mutagens. Methods: We conducted a population-based case-control study in three rural Pennsylvania counties of persons born 1921–1968 and residing in the area between 2000–2008. Twenty seven MPN cases and 292 controls were recruited through random digit dialing. Subjects were genotyped and odds ratios estimated for a select set of polymorphisms in environmentally sensitive genes that might implicate specific environmental mutagens if found to be associated with a disease. Results: The presence of NAT2 slow acetylator genotype, and CYP1A2, GSTA1, and GSTM3 variants were associated with an average 3–5 fold increased risk. Conclusions: Exposures, such as to aromatic compounds, whose toxicity is modified by genotypes associated with outcome in our analysis may play a role in the environmental etiology of MPNs.

Electromyographic analysis of an eccentric calf muscle exercise in persons with and without Achilles tendinopathy.

Science.gov (United States)

Reid, Duncan; McNair, Peter J; Johnson, Shelley; Potts, Geoff; Witvrouw, Erik; Mahieu, Nele

2012-08-01

To compare surface electromyographic (EMG) activity of the gastrocnemius and soleus muscles between persons with and without Achilles tendinopathy (AT) during an eccentric muscle exercise in different knee joint positions. Repeated measures design. Research laboratory. Participants (n = 18) diagnosed with AT and 18 control subjects were recruited. Gastrocnemius and soleus muscle activity was examined by surface (EMG) during extended and flexed knee joint conditions while performing the eccentric training technique. The EMG data were expressed as a percentage of a maximum voluntary contraction (MVC). EMG activity was notably higher (mean difference: 10%, effect size: 0.59) in those subjects with AT. Irrespective of the presence of AT, there was a significant interaction effect between muscle and joint position. The gastrocnemius muscle was significantly more active in the extended knee condition and soleus muscle activity was unchanged across joint positions. The results indicated that the presence of AT influenced calf muscle activity levels during performance of the eccentric exercise. There were differences in muscle activity during the extended and flexed knee conditions. This result does support performing Alfredson, Pietila, Jonsson, and Lorentzon (1998) eccentric exercise in an extended knee position but the specific effects of the knee flexed position on the Achilles tendon during eccentric exercise have yet to be determined, particularly in those with AT. Copyright © 2011 Elsevier Ltd. All rights reserved.

Feeding soy or fish meal to Alaskan reindeer (Rangifer tarandus tarandus – effects on animal performance and meat quality

Directory of Open Access Journals (Sweden)

Greg Finstad

2009-01-01

ökning ingick 14 renar (8 kastrerade sarvar (härkaroch 6 vajor för att jämföra effekter av två olika renfoder (baserade på korn, hö och soja- (SBM eller fiskmjöl (WFM som proteintillskott med avseende på tillväxt, foderutnyttjande och köttkvalitet. Köttprover från naturbetande renar (n=4; 2 härkar och 2 vajor från Seward Peninsula inkluderades i studien för att representera kvaliteten på traditionellt producerat renkött från Alaska. Inga signifikanta skillnader i tillväxt observerades, varken mellan SBM- och WFM-grupperna eller mellan härkar och vajor. Foderutnyttjandet var dock signifikant bättre hos WFM-renarna. Slaktutbytet var högst för renarna i SBM-gruppen, däremot rapporterades inga skillnader i levandevikt, slaktkroppsegenskaper, pH-värde och temperatur i ytterfilén, skärmotstånd, färg eller vattenhållande förmåga i köttet när de tre grupperna av renar jämfördes (SBM, WFM och naturbetande djur. Köttet från de naturbetande renarna hade det signifikant högsta innehållet av både omega-3-fettsyror och av fleromättade fettsyror. Kött från SBM-renarna hade det högsta innehållet av triglycerider och det lägsta innehållet av fosfolipider jämfört med de andra två grupperna. Den tränade smakpanelen kunde inte hitta några skillnader i sensoriska egenskaper hos köttet från renarna i de tre olika grupperna. I en konsumentundersökning rapporterades kommentarer om olika ”vilt-relaterade” bismaker i kött från naturbetande renar (24% av konsumenterna och från WFM-gruppen (15% av konsumenterna, men inga ”fisk-liknande” bismaker i köttet kunde påvisas. Att byta ut sojamjöl mot fiskmjöl som proteintillskott i renfoder hade inga negativa effekter på renarnas tillväxt, foderutnyttjande eller på renköttets kvalitet.

Collateral sensitivity to cisplatin in KB-8-5-11 drug-resistant cancer cells.

Science.gov (United States)

Doherty, Ben; Lawlor, Denise; Gillet, Jean-Pierre; Gottesman, Michael; O'Leary, John J; Stordal, Britta

2014-01-01

KB-8-5-11 cells are a drug-resistant cervical cell model that overexpresses ABCB1 (P-glycoprotein). KB-8-5-11 has become sensitive to non-ABCB1 substrate cisplatin. Understanding the mechanism of collateral sensitivity to cisplatin may lead to biomarker discovery for platinum sensitivity in patients with cancer. A Taqman low-density array was used to characterize the expression of 380 genes previously associated with chemoresistance. Identified pathways were further analyzed using cytotoxicity assays, metabolomics and western blots. KB-8-5-11 cells were sensitive to CuSO4 and the glutathione inhibitor buthionine sulphoximine. Expression of ATPase, Cu(2+) transporting alpha (ATP7A) and ATP7B were decreased at the protein and gene levels respectively in KB-8-5-11. KB-8-5-11 had decreased gene expression of glutathione S-transferase pi 1 (GSTP1), GSTA4 and GSTK1. Cisplatin treatment significantly lowered total cellular glutathione in parental KB-3-1 cells. Glutathione also tended to be lower in KB-8-5-11 cells compared to KB-3-1 cells. KB-8-5-11 cells have alterations in their copper transporters and glutathione metabolism, contributing to their cisplatin-sensitive phenotype.

Medizinbibliotheken: Information

Directory of Open Access Journals (Sweden)

Bauer, Bruno

2014-12-01

Full Text Available [english] The focus of the current issue 3/2014 of GMS Medizin – Bibliothek – Information is the annual conference 2014 of the German Medical Libraries Association in Mannheim. The motto of the conference was “Medical libraries: Information”. The authors in this issue are Michaele Adam (Bibliometrics 2.0 – Altmetrics in Medicine, Bruno Bauer (Open access cooperation in Austria: Open Access Network Austria and Austria – recent developments since 2012, Fabian Gail & Ulrich Korwitz (Market and strategy – results of the ZB MED market study, Sabine Gehrlein (Library goes Anatomy: Anatomical teaching media at Heidelberg University Library, Kaja Scheliga (Opening science: New publication forms in science, Ulrike Ostrzinski (The four types of social media user in the academic and research community. Results of a nationwide study, Sandra Pfob & Alena Ittner (First aid for library use on PC: webinars increase library visits, reach everyone, save costs, Simone Waldboth (Integration of e-learning in the lecture “Information Literacy” at the Provincial College for Health-Care Professions Claudiana, Maike Piegler (The pick up box of the library of the Hamburg medical association – a way to bring scientific information to medical specialists and Christoph Wehrmüller & Heidrun Janka (Medical : Information – Annual meeting 2014 of the German MLA, September 22 to 24 in Mannheim.Furthermore this focus issue features articles from Bruno Bauer (: transformation strategies for subscription-based journaleport on the 8 Open Access Days at Cologne, September 8–9 2014, Eike Hentschel (German MLA News; Pioneer projects in medical libraries 2014: Introduction of the winners; Pioneer projects in medical libraries 2015 – Announcement and Franz J. Kühnen (Klaus Gerber 1934–2014.

Backset-stationary and during car driving.

Science.gov (United States)

Jonsson, Bertil; Stenlund, Hans; Björnstig, Ulf

2008-12-01

The aim of the study was to measure and analyze backset, defined as the horizontal distance between the back of the occupant's head and a point located on the ventral/top aspect of the sewn rim of the head restraint, with the car stationary and during driving, in the driver's position in a modern car. A population of 65 subjects, 35 males and 30 females, was studied in a Volvo V70 car, model year 2007. The subjects were studied in the driver's position, in a self-selected posture. Stationary backset was measured with the technique described by Jonsson et al. (2007) and backset during driving with video analysis. Descriptive data were calculated, and variability and correlation analyses were performed. A t-test was used to test differences of means. Significance level was set to 0.05. In comparison to stationary backset, mean backset during driving was 43 mm greater in males and 41 mm greater in females. Driving backset was 44 mm larger in males than in females. Driving backset was moderately correlated (0.37-0.43) to stature, seated height, and seat back angle in males and moderately correlated (0.44-0.52) to hip width, waist circumference, and weight in females. The overall intraclass correlation coefficient for backset during driving was 0.81 (CI: 0.75-0.86). These results may be of use in designing future updates of test protocols/routines for geometric backset, such as RCAR and RCAR-IIWPG.

Photothrombosis-induced infarction of the mouse cerebral cortex is not affected by the Nrf2-activator sulforaphane.

Directory of Open Access Journals (Sweden)

Michelle J Porritt

Full Text Available Sulforaphane-induced activation of the transcription factor NF-E2 related factor 2 (Nrf2 or the gene Nfe2l2 and subsequent induction of the phase II antioxidant system has previously been shown to exert neuroprotective action in a transient model of focal cerebral ischemia. However, its ability to attenuate functional and cellular deficits after permanent focal cerebral ischemia is not clear. We assessed the neuroprotective effects of sulforaphane in the photothrombotic model of permanent focal cerebral ischemia. Sulforaphane was administered (5 or 50 mg/kg, i.p. after ischemic onset either as a single dose or as daily doses for 3 days. Sulforaphane increased transcription of Nrf2, Hmox1, GCLC and GSTA4 mRNA in the brain confirming activation of the Nrf2 system. Single or repeated administration of sulforaphane had no effect on the infarct volume, nor did it reduce the number of activated glial cells or proliferating cells when analyzed 24 and 72 h after stroke. Motor-function as assessed by beam-walking, cylinder-test, and adhesive test, did not improve after sulforaphane treatment. The results show that sulforaphane treatment initiated after photothrombosis-induced permanent cerebral ischemia does not interfere with key cellular mechanisms underlying tissue damage.

Photothrombosis-induced infarction of the mouse cerebral cortex is not affected by the Nrf2-activator sulforaphane.

Science.gov (United States)

Porritt, Michelle J; Andersson, Helene C; Hou, Linda; Nilsson, Åsa; Pekna, Marcela; Pekny, Milos; Nilsson, Michael

2012-01-01

Sulforaphane-induced activation of the transcription factor NF-E2 related factor 2 (Nrf2 or the gene Nfe2l2) and subsequent induction of the phase II antioxidant system has previously been shown to exert neuroprotective action in a transient model of focal cerebral ischemia. However, its ability to attenuate functional and cellular deficits after permanent focal cerebral ischemia is not clear. We assessed the neuroprotective effects of sulforaphane in the photothrombotic model of permanent focal cerebral ischemia. Sulforaphane was administered (5 or 50 mg/kg, i.p.) after ischemic onset either as a single dose or as daily doses for 3 days. Sulforaphane increased transcription of Nrf2, Hmox1, GCLC and GSTA4 mRNA in the brain confirming activation of the Nrf2 system. Single or repeated administration of sulforaphane had no effect on the infarct volume, nor did it reduce the number of activated glial cells or proliferating cells when analyzed 24 and 72 h after stroke. Motor-function as assessed by beam-walking, cylinder-test, and adhesive test, did not improve after sulforaphane treatment. The results show that sulforaphane treatment initiated after photothrombosis-induced permanent cerebral ischemia does not interfere with key cellular mechanisms underlying tissue damage.

Early experiences of planning stereotactic radiosurgery using 3D printed models of eyes with uveal melanomas

Directory of Open Access Journals (Sweden)

Furdová A

2017-01-01

Full Text Available Alena Furdová,1 Miron Sramka,2 Andrej Thurzo,3 Adriana Furdová3 1Department of Ophthalmology, Faculty of Medicine, Comenius University, 2Department of Stereotactic Radiosurgery, St Elisabeth Cancer Inst and St Elisabeth University College of Health and Social Work, 3Department of Simulation and Virtual Medical Education, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic Objective: The objective of this study was to determine the use of 3D printed model of an eye with intraocular tumor for linear accelerator-based stereotactic radiosurgery.Methods: The software for segmentation (3D Slicer created virtual 3D model of eye globe with tumorous mass based on tissue density from computed tomography and magnetic resonance imaging data. A virtual model was then processed in the slicing software (Simplify3D® and printed on 3D printer using fused deposition modeling technology. The material that was used for printing was polylactic acid.Results: In 2015, stereotactic planning scheme was optimized with the help of 3D printed model of the patient’s eye with intraocular tumor. In the period 2001–2015, a group of 150 patients with uveal melanoma (139 choroidal melanoma and 11 ciliary body melanoma were treated. The median tumor volume was 0.5 cm3 (0.2–1.6 cm3. The radiation dose was 35.0 Gy by 99% of dose volume histogram.Conclusion: The 3D printed model of eye with tumor was helpful in planning the process to achieve the optimal scheme for irradiation which requires high accuracy of defining the targeted tumor mass and critical structures. Keywords: 3D printing, uveal melanoma, stereotactic radiosurgery, linear accelerator, intraocular tumor, stereotactic planning scheme

Conference Report: Drug Metabolism Discussion Group Short Meeting: microsampling--the next big thing. Alderley Park, Macclesfield, UK, 14 March 2012.

Science.gov (United States)

Jackson-Addie, Kirsty; Woods, Karen; Muir, Allan; Smith, Christopher; Higton, David

2012-12-01

On behalf of the Drug Metabolism Discussion Group, Regulatory Bioanalysis AstraZeneca (UK) recently organized and hosted an extremely successful Drug Metabolism Discussion Group Short Meeting on 'microsampling--the next big thing'. This attracted over 140 delegates and a strong line up of presenters of respected scientists within the field. This meeting focused on the impact of taking a reduced sample (5-20 µl) from an animal, or later in the clinic, particularly neonates. The agenda covered the spectrum of microsampling, from capillary plasma microsampling, as championed by Ove Jonsson and Kristian Königsson, through to dried blood spots. The day was split up in to three sections, the morning concentrating on the sampling aspects from animals. A highlight of the first section was the 'poster blitz' where four poster presenters gave a quick overview of their work. This introduced the poster session and created a good atmosphere for general debate between the delegates. The mid-session saw the bioanalytical challenges discussed from the discovery to the preclinical stage. To encourage interaction between the presenters and the audience, a panel discussion was used that led to interesting insights into study design from toxicological and bioanalytical viewpoints. The final session was left to clinical aspects of microsampling and a particularly interesting presentation from Hitesh Pandya from the Pediatric Respiratory Medicine Department (University of Leicester, Leicester, UK). An eloquent and hard-hitting presentation put into perspective the importance of advancements in this field that enables sample to be taken in a noninvasive manner. The meeting was well received with excellent feedback from all concerned.

Research and Development Program in Reactor Diagnostics and Monitoring with Neutron Noise Methods, Stage 16

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Pazsit, Imre; Dykin, Victor; Jonsson, Anders; Demaziere, Christophe (Chalmers Univ. of Technology, Dept. of Nuclear Engineering, Goeteborg (Sweden))

2010-12-15

This report gives an account of the work performed by the Dept. of Nuclear Engineering, Chalmers Univ. of Technology, in the frame of a research contract with the Swedish Radiation Safety Authority (SSM), contract No. SSM 2009/2093. The present report is based on work performed by Imre Pazsit, Victor Dykin, Anders Jonsson and Christophe Demaziere, with Imre Pazsit being the project leader. This report describes the results obtained during Stage 16 of a long-term research and development program concerning the development of diagnostics and monitoring methods for nuclear reactors. The long-term goals are elaborated in more detail in e.g. the Final Reports of Stage 1 and 2 (SKI Report 95:14 and 96:50, Pazsit et al. 1995, 1996). Results up to Stage 15 were reported in (Pazsit et al. 1995, 1996, 1997, 1998, 1999, 2000, 2001, 2003a, 2003b; Demaziere et al, 2004; Sunde et al, 2006; Pazsit et al. 2008, 2009). A brief proposal for the continuation of this program in Stage 17 is also given at the end of the report. The program executed in Stage 16 consists of four parts as follows: - An overview of the present status of experience with BWR stability; - An investigation of the significance of the properties of the noise source for BWR instability; - Study of the dynamics of molten salt systems: construction of the adjoint and calculating the space dependent noise induced by propagating perturbations in the fuel; - A specific study of some novel methods of analysis of non-linear and non-stationary processes

Inertial forces and the foundations of optical geometry

International Nuclear Information System (INIS)

Jonsson, Rickard

2006-01-01

Assuming a general timelike congruence of worldlines as a reference frame, we derive a covariant general formalism of inertial forces in general relativity. Inspired by the works of Abramowicz et al (see e.g. Abramowicz and Lasota 1997 Class. Quantum Grav. 14 A23-30), we also study conformal rescalings of spacetime and investigate how these affect the inertial force formalism. While many ways of describing spatial curvature of a trajectory have been discussed in papers prior to this, one particular prescription (which differs from the standard projected curvature when the reference congruence is shearing), appears novel. For the particular case of a hypersurface-forming congruence, using a suitable rescaling of spacetime, we show that a geodesic photon always follows a line that is spatially straight with respect to the new curvature measure. This fact is intimately connected to Fermat's principle, and allows for a certain generalization of the optical geometry as will be further pursued in a companion paper (Jonsson and Westman 2006 Class. Quantum Grav. 23 61). For the particular case when the shear tensor vanishes, we present the inertial force equation in a three-dimensional form (using the bold-face vector notation), and note how similar it is to its Newtonian counterpart. From the spatial curvature measures that we introduce, we derive corresponding covariant differentiations of a vector defined along a spacetime trajectory. This allows us to connect the formalism of this paper to that of Jantzen and co-workers (see e.g. Bini et al 1997 Int. J. Mod. Phys. D 6 143-98)

The effect of nonlinearity in CO2 heating rates on the attribution of stratospheric ozone and temperature changes

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T. G. Shepherd

2009-11-01

Full Text Available An analysis of the attribution of past and future changes in stratospheric ozone and temperature to anthropogenic forcings is presented. The analysis is an extension of the study of Shepherd and Jonsson (2008 who analyzed chemistry-climate simulations from the Canadian Middle Atmosphere Model (CMAM and attributed both past and future changes to changes in the external forcings, i.e. the abundances of ozone-depleting substances (ODS and well-mixed greenhouse gases. The current study is based on a new CMAM dataset and includes two important changes. First, we account for the nonlinear radiative response to changes in CO2. It is shown that over centennial time scales the radiative response in the upper stratosphere to CO2 changes is significantly nonlinear and that failure to account for this effect leads to a significant error in the attribution. To our knowledge this nonlinearity has not been considered before in attribution analysis, including multiple linear regression studies. For the regression analysis presented here the nonlinearity was taken into account by using CO2 heating rate, rather than CO2 abundance, as the explanatory variable. This approach yields considerable corrections to the results of the previous study and can be recommended to other researchers. Second, an error in the way the CO2 forcing changes are implemented in the CMAM was corrected, which significantly affects the results for the recent past. As the radiation scheme, based on Fomichev et al. (1998, is used in several other models we provide some description of the problem and how it was fixed.

Research and Development Program in Reactor Diagnostics and Monitoring with Neutron Noise Methods, Stage 16

International Nuclear Information System (INIS)

Pazsit, Imre; Dykin, Victor; Jonsson, Anders; Demaziere, Christophe

2010-12-01

This report gives an account of the work performed by the Dept. of Nuclear Engineering, Chalmers Univ. of Technology, in the frame of a research contract with the Swedish Radiation Safety Authority (SSM), contract No. SSM 2009/2093. The present report is based on work performed by Imre Pazsit, Victor Dykin, Anders Jonsson and Christophe Demaziere, with Imre Pazsit being the project leader. This report describes the results obtained during Stage 16 of a long-term research and development program concerning the development of diagnostics and monitoring methods for nuclear reactors. The long-term goals are elaborated in more detail in e.g. the Final Reports of Stage 1 and 2 (SKI Report 95:14 and 96:50, Pazsit et al. 1995, 1996). Results up to Stage 15 were reported in (Pazsit et al. 1995, 1996, 1997, 1998, 1999, 2000, 2001, 2003a, 2003b; Demaziere et al, 2004; Sunde et al, 2006; Pazsit et al. 2008, 2009). A brief proposal for the continuation of this program in Stage 17 is also given at the end of the report. The program executed in Stage 16 consists of four parts as follows: - An overview of the present status of experience with BWR stability; - An investigation of the significance of the properties of the noise source for BWR instability; - Study of the dynamics of molten salt systems: construction of the adjoint and calculating the space dependent noise induced by propagating perturbations in the fuel; - A specific study of some novel methods of analysis of non-linear and non-stationary processes

Generalizing optical geometry

International Nuclear Information System (INIS)

Jonsson, Rickard; Westman, Hans

2006-01-01

We show that by employing the standard projected curvature as a measure of spatial curvature, we can make a certain generalization of optical geometry (Abramowicz M A and Lasota J-P 1997 Class. Quantum Grav. A 14 23-30). This generalization applies to any spacetime that admits a hypersurface orthogonal shearfree congruence of worldlines. This is a somewhat larger class of spacetimes than the conformally static spacetimes assumed in standard optical geometry. In the generalized optical geometry, which in the generic case is time dependent, photons move with unit speed along spatial geodesics and the sideways force experienced by a particle following a spatially straight line is independent of the velocity. Also gyroscopes moving along spatial geodesics do not precess (relative to the forward direction). Gyroscopes that follow a curved spatial trajectory precess according to a very simple law of three-rotation. We also present an inertial force formalism in coordinate representation for this generalization. Furthermore, we show that by employing a new sense of spatial curvature (Jonsson R 2006 Class. Quantum Grav. 23 1)) closely connected to Fermat's principle, we can make a more extensive generalization of optical geometry that applies to arbitrary spacetimes. In general this optical geometry will be time dependent, but still geodesic photons move with unit speed and follow lines that are spatially straight in the new sense. Also, the sideways experienced (comoving) force on a test particle following a line that is straight in the new sense will be independent of the velocity

Sediment Sources and Transport Pathway Identification Based on Grain-Size Distributions on the SW Coast of Portugal

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Xiaoqin Du

2015-01-01

Full Text Available Espichel-Sines is an embayed coast in SW Portugal, consisting of two capes at both extremities, a tidal inlet and associated ebb tidal delta, a barrier spit, sandy beaches, sea cliffs, and a submarine canyon. Beach berm, backshore, near shore and inner shelf sediment samples were taken. Samples were analyzed for their grain-size compositions. This study ranks the hypothetical sediment sources influences on the sediment distributions in the study area using the multivariate Empirical Orthogonal Function (EOF techniques. Transport pathways in this study were independently identified using the grain size trend analysis (GSTA technique to verify the EOF findings. The results show that the cliff-erosion sediment is composed of pebbles and sand and is the most important sediment source for the entire embayment. The sediment at the inlet mouth is a mixture of pebbles, sand, silt, and clay, which is a minor sediment source that only has local influence. The overall grain-size distributions on the shelf are dominated by the sand except for the high mud content around the tidal delta front in the northern embayment. Sediment transport patterns on the inner shelf at the landward and north sides of the canyon head are landward and northward along the barrier spit, respectively. On the south side of the canyon head, the prevailing sediment transport is seaward. Sediment transport occurs in both directions along the shore.

Targeting Glutathione-S Transferase Enzymes in Musculoskeletal Sarcomas: A Promising Therapeutic Strategy

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Michela Pasello

2011-01-01

Full Text Available Recent studies have indicated that targeting glutathione-S-transferase (GST isoenzymes may be a promising novel strategy to improve the efficacy of conventional chemotherapy in the three most common musculoskeletal tumours: osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma. By using a panel of 15 drug-sensitive and drug-resistant human osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma cell lines, the efficay of the GST-targeting agent 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthiohexanol (NBDHEX has been assessed and related to GST isoenzymes expression (namely GSTP1, GSTA1, GSTM1, and MGST. NBDHEX showed a relevant in vitro activity on all cell lines, including the drug-resistant ones and those with higher GSTs levels. The in vitro activity of NBDHEX was mostly related to cytostatic effects, with a less evident apoptotic induction. NBDHEX positively interacted with doxorubicin, vincristine, cisplatin but showed antagonistic effects with methotrexate. In vivo studies confirmed the cytostatic efficay of NBDHEX and its positive interaction with vincristine in Ewing's sarcoma cells, and also indicated a positive effect against the metastatisation of osteosarcoma cells. The whole body of evidence found in this study indicated that targeting GSTs in osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma may be an interesting new therapeutic option, which can be considered for patients who are scarcely responsive to conventional regimens.

Collision probability in two-dimensional lattice by ray-trace method and its applications to cell calculations

International Nuclear Information System (INIS)

Tsuchihashi, Keichiro

1985-03-01

A series of formulations to evaluate collision probability for multi-region cells expressed by either of three one-dimensional coordinate systems (plane, sphere and cylinder) or by the general two-dimensional cylindrical coordinate system is presented. They are expressed in a suitable form to have a common numerical process named ''Ray-Trace'' method. Applications of the collision probability method to two optional treatments for the resonance absorption are presented. One is a modified table-look-up method based on the intermediate resonance approximation, and the other is a rigorous method to calculate the resonance absorption in a multi-region cell in which nearly continuous energy spectra of the resonance neutron range can be solved and interaction effect between different resonance nuclides can be evaluated. Two works on resonance absorption in a doubly heterogeneous system with grain structure are presented. First, the effect of a random distribution of particles embedded in graphite diluent on the resonance integral is studied. Next, the ''Accretion'' method proposed by Leslie and Jonsson to define the collision probability in a doubly heterogeneous system is applied to evaluate the resonance absorption in coated particles dispersed in fuel pellet of the HTGR. Several optional models are proposed to define the collision rates in the medium with the microscopic heterogeneity. By making use of the collision probability method developed by the present study, the JAERI thermal reactor standard nuclear design code system SRAC has been developed. Results of several benchmark tests for the SRAC are presented. The analyses of critical experiments of the SHE, DCA, and FNR show good agreement of critical masses with their experimental values. (J.P.N.)

Isoenzyme-specific up-regulation of glutathione transferase and aldo-keto reductase mRNA expression by dietary quercetin in rat liver.

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Odbayar, Tseye-Oidov; Kimura, Toshinori; Tsushida, Tojiro; Ide, Takashi

2009-05-01

The impact of quercetin on the mRNA expression of hepatic enzymes involved in drug metabolism was evaluated with a DNA microarray and real-time PCR. Male Sprague-Dawley rats were fed an experimental diet containing either 0, 2.5, 5, 10, or 20 g/kg of quercetin for 15 days. The DNA microarray analysis of the gene expression profile in pooled RNA samples from rats fed diets containing 0, 5, and 20 g/kg of quercetin revealed genes of some isoenzymes of glutathione transferase (Gst) and aldo-keto reductase (Akr) to be activated by this flavonoid. Real-time PCR conducted with RNA samples from individual rats fed varying amounts of quercetin together with the microarray analysis showed that quercetin caused marked dose-dependent increases in the mRNA expression of Gsta3, Gstp1, and Gstt3. Some moderate increases were also noted in the mRNA expression of isoenzymes belonging to the Gstm class. Quercetin also dose-dependently increased the mRNA expression of Akr1b8 and Akr7a3. However, it did not affect the parameters of the other Gst and Akr isoenzymes. It is apparent that quercetin increases the mRNA expression of Gst and Akr involved in drug metabolism in an isoenzyme-specific manner. Inasmuch as Gst and Akr isoenzymes up-regulated in their gene expression are involved in the prevention and attenuation of cancer development, this consequence may account for the chemopreventive propensity of quercetin.

The Amelioration of N-Acetyl-p-Benzoquinone Imine Toxicity by Ginsenoside Rg3: The Role of Nrf2-Mediated Detoxification and Mrp1/Mrp3 Transports

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Sang Il Gum

2013-01-01

Full Text Available Previously, we found that Korean red ginseng suppressed acetaminophen (APAP-induced hepatotoxicity via alteration of its metabolic profile involving GSTA2 induction and that ginsenoside Rg3 was a major component of this gene induction. In the present study, therefore, we assessed the protective effect of Rg3 against N-acetyl-p-benzoquinone imine (NAPQI, a toxic metabolic intermediate of APAP. Excess NAPQI resulted in GSH depletion with increases in the ALT and AST activities in H4IIE cells. Rg3 pretreatment reversed GSH depletion by NAPQI. Rg3 resulted in increased mRNA levels of the catalytic and modulatory subunit of glutamate cysteine ligase (GCL, the rate-limiting steps in GSH synthesis and subsequently increased GSH content. Rg3 increased levels of nuclear Nrf2, an essential transcriptional factor of these genes. The knockdown or knockout of the Nrf2 gene abrogated the inductions of mRNA and protein by Rg3. Abolishment of the reversal of GSH depletion by Rg3 against NAPQI was observed in Nrf2-deficient cells. Rg3 induced multidrug resistance-associated protein (Mrp 1 and Mrp3 mRNA levels, but not in Nrf2-deficient cells. Taken together, these results demonstrate that Rg3 is efficacious in protecting hepatocytes against NAPQI insult, due to GSH repletion and coordinated gene regulations of GSH synthesis and Mrp family genes by Nrf2.

Microarray analysis of altered gene expression in murine fibroblasts transformed by nickel(II) to nickel(II)-resistant malignant phenotype

International Nuclear Information System (INIS)

Kowara, Renata; Karaczyn, Aldona; Cheng, Robert Y.S.; Salnikow, Konstantin; Kasprzak, Kazimierz S.

2005-01-01

B200 cells are Ni(II)-transformed mouse BALB/c-3T3 fibroblasts displaying a malignant phenotype and increased resistance to Ni(II) toxicity. In an attempt to find genes whose expression has been altered by the transformation, the Atlas Mouse Stress/Toxicology cDNA Expression Array (Clontech Laboratories, Inc., Palo Alto, CA) was used to analyze the levels of gene expression in both parental and Ni(II)-transformed cells. Comparison of the results revealed a significant up- or downregulation of the expression of 62 of the 588 genes present in the array (approximately 10.5%) in B200 cells. These genes were assigned to different functional groups, including transcription factors and oncogenes (9/14; fractions in parentheses denote the number of up-regulated versus the total number of genes assigned to this group), stress and DNA damage response genes (11/12), growth factors and hormone receptors (6/9), metabolism (7/7), cell adhesion (2/7), cell cycle (3/6), apoptosis (3/4), and cell proliferation (2/3). Among those genes, overexpression of beta-catenin and its downstream targets c-myc and cyclin D1, together with upregulated cyclin G, points at the malignant character of B200 cells. While the increased expression of glutathione (GSH) synthetase, glutathione-S-transferase A4 (GSTA4), and glutathione-S-transferase theta (GSTT), together with high level of several genes responding to oxidative stress, suggests the enforcement of antioxidant defenses in Ni-transformed cells

Influence of production system, age an sex on carcass parameters and some biochemical meat quality characteristics of reindeer (Rangifer tarandus tarandus L.

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Sabine Sampels

2005-03-01

studie var att jämföra lipidklassammansättningen och IMF i relation till slaktkroppens vikt, form och mängden putsfett och att undersöka hur dessa parametrar påverkas av renarnas kön, ålder och olika typer av foder (bete och pellets. Fem grupper renar ingick i studien (totalt 38 djur. Två grupper kalvar utfodrades med två sorters pellets med olika fettsammansättning under två månader före slakt. Den ena gruppen fick normala pellets (CPD (Renfor Bas medan den andra gruppen fick pellets som hade en tillsats av linfrökaka (LPD för att öka mängden n-3 fettsyror i fodret. Dessutom ingick tre grupper betesdjur i studien: vajor, sarvar och kalvar. Utfodring med pellets gav slaktkroppar med bättre klassning, högre slaktvikter och mer putsfett jämfört med slaktkroppar från betande kalvar. Vajorna hade de högsta och betande kalvar de lägsta slaktvikterna, minst putsfett och lägst halt av IMF. Utfodringen med pellets gav ingen signifikant skillnad i IMF mellan betande och utfodrade renkalvar. Vi fann ingen skillnad i lipidklassammansättning mellan de två utfodrade kalvgrupperna, men köttet från de betande kalvarna hade en högre halt av fosfolipider. Vi kunde också identifiera och kvantifiera squalen som en komponent i intramuskulärt fett i renkött.

Control of the heart rate of rat embryos during the organogenic period

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Ritchie HE

2016-11-01

Full Text Available Helen E Ritchie,1 Carolina Ragnerstam,2 Elin Gustafsson,2 Johanna M Jonsson,2 William S Webster2 1Discipline of Biomedical Science, Sydney Medical School, University of Sydney, Lidcombe, 2Department of Anatomy and Histology, Sydney Medical School, University of Sydney, Sydney, NSW, Australia Abstract: The aim of this study was to gain insight into whether the first trimester embryo could control its own heart rate (HR in response to hypoxia. The gestational day 13 rat embryo is a good model for the human embryo at 5–6 weeks gestation, as the heart is comparable in development and, like the human embryo, has no functional autonomic nerve supply at this stage. Utilizing a whole-embryo culture technique, we examined the effects of different pharmacological agents on HR under normoxic (95% oxygen and hypoxic (20% oxygen conditions. Oxygen concentrations ≤60% caused a concentration-dependent decrease in HR from normal levels of ~210 bpm. An adenosine agonist, AMP-activated protein kinase (AMPK activator and KATP channel opener all caused bradycardia in normoxic conditions; however, putative antagonists for these systems failed to prevent or ameliorate hypoxia-induced bradycardia. This suggests that the activation of one or more of these systems is not the primary cause of the observed hypoxia-induced bradycardia. Inhibition of oxidative phosphorylation also decreased HR in normoxic conditions, highlighting the importance of ATP levels. The β-blocker metoprolol caused a concentration-dependent reduction in HR supporting reports that β1-adrenergic receptors are present in the early rat embryonic heart. The cAMP inducer colforsin induced a positive chronotropic effect in both normoxic and hypoxic conditions. Overall, the embryonic HR at this stage of development is responsive to the level of oxygenation, probably as a consequence of its influence on ATP production. Keywords: embryonic heart rate, embryo, bradycardia, in vitro, ATP, hypoxia

Calibration of Recoil-In-Vacuum attenuations from first principles: comparison with recent experimental data on Fe isotopes

International Nuclear Information System (INIS)

Stone, Nicholas James; Stone, Jirina Rikovska; Stuchbery, Andrew E.; Jonsson, Per

2015-01-01

Precession of aligned nuclear spin systems in ions recoiling from the target into vacuum (RIV) with consequent attenuation of angular distributions of emitted radiation is, in principle, a versatile method for measurement of g-factors of nuclear excited states of lifetimes in the pico-second range (Stone et al., Phys. Rev. Lett., 94, 192501, 2005 and Stuchbery and Stone, Phys. Rev. C, 76, 034307, 2007). Calibration of the observed attenuations has been achieved in favourable cases through comparison with measurements on states having previously known g-factors and lifetimes. The general lack of suitable states with known g-factors has limited application of the RIV method. This paper concerns the present status of efforts to describe the states of excited ions recoiling into vacuum in detail so that the average interaction can be estimated with useful precision from a-priori theory. The calculations use the GRASP2K package (Froese-Fischer et al. 1997 and Jonsson, Comp. Phys. Comm., 177, 597, 2007 & 184, 2197, 2013) to obtain, for each recoiling ion change state, the individual possible electronic states, their configurations, lifetimes and hyperfine interactions. It is assumed that all possible ionic states are produced, up to a chosen excitation energy. This energy is selected to approximate the energy at which all states have lifetimes far shorter than the nuclear state of interest. It is further assumed that the ionic state total electron angular momenta are randomly oriented in space. The first estimates of the average attenuation of emission distributions, as a function of the product g τ of the nuclear state g-factor and mean lifetime, used an averaged precession frequency obtained neglecting transitions between electronic states. Improved calculations, which include such transitions, are described

Increased accumulation of 4-hydroxynonenal adducts in female GSTA4/PPAR alpha double knockout mice enhance steatosis and inflammation in a model of pediatric nonalcoholic fatty liver disease

Science.gov (United States)

Hepatocellular injury resulting from increased lipid peroxidation products and oxidative stress is considered a potential mechanism driving the progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitsis (NASH). To test the significance of lipid peroxidation and protein...

Caloric restriction and intermittent fasting alter hepatic lipid droplet proteome and diacylglycerol species and prevent diabetes in NZO mice.

Science.gov (United States)

Baumeier, Christian; Kaiser, Daniel; Heeren, Jörg; Scheja, Ludger; John, Clara; Weise, Christoph; Eravci, Murat; Lagerpusch, Merit; Schulze, Gunnar; Joost, Hans-Georg; Schwenk, Robert Wolfgang; Schürmann, Annette

2015-05-01

Caloric restriction and intermittent fasting are known to improve glucose homeostasis and insulin resistance in several species including humans. The aim of this study was to unravel potential mechanisms by which these interventions improve insulin sensitivity and protect from type 2 diabetes. Diabetes-susceptible New Zealand Obese mice were either 10% calorie restricted (CR) or fasted every other day (IF), and compared to ad libitum (AL) fed control mice. AL mice showed a diabetes prevalence of 43%, whereas mice under CR and IF were completely protected against hyperglycemia. Proteomic analysis of hepatic lipid droplets revealed significantly higher levels of PSMD9 (co-activator Bridge-1), MIF (macrophage migration inhibitor factor), TCEB2 (transcription elongation factor B (SIII), polypeptide 2), ACY1 (aminoacylase 1) and FABP5 (fatty acid binding protein 5), and a marked reduction of GSTA3 (glutathione S-transferase alpha 3) in samples of CR and IF mice. In addition, accumulation of diacylglycerols (DAGs) was significantly reduced in livers of IF mice (P=0.045) while CR mice showed a similar tendency (P=0.062). In particular, 9 DAG species were significantly reduced in response to IF, of which DAG-40:4 and DAG-40:7 also showed significant effects after CR. This was associated with a decreased PKCε activation and might explain the improved insulin sensitivity. In conclusion, our data indicate that protection against diabetes upon caloric restriction and intermittent fasting associates with a modulation of lipid droplet protein composition and reduction of intracellular DAG species. Copyright © 2015. Published by Elsevier B.V.

Maternal obesity and tobacco use modify the impact of genetic variants on the occurrence of conotruncal heart defects.

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Tang, Xinyu; Nick, Todd G; Cleves, Mario A; Erickson, Stephen W; Li, Ming; Li, Jingyun; MacLeod, Stewart L; Hobbs, Charlotte A

2014-01-01

Conotruncal heart defects (CTDs) are among the most severe birth defects worldwide. Studies of CTDs indicate both lifestyle behaviors and genetic variation contribute to the risk of CTDs. Based on a hybrid design using data from 616 case-parental and 1645 control-parental triads recruited for the National Birth Defects Prevention Study between 1997 and 2008, we investigated whether the occurrence of CTDs is associated with interactions between 921 maternal and/or fetal single nucleotide polymorphisms (SNPs) and maternal obesity and tobacco use. The maternal genotypes of the variants in the glutamate-cysteine ligase, catalytic subunit (GCLC) gene and the fetal genotypes of the variants in the glutathione S-transferase alpha 3 (GSTA3) gene were associated with an elevated risk of CTDs among obese mothers. The risk of delivering infants with CTDs among obese mothers carrying AC genotype for a variant in the GCLC gene (rs6458939) was 2.00 times the risk among those carrying CC genotype (95% confidence interval: 1.41, 2.38). The maternal genotypes of several variants in the glutathione-S-transferase (GST) family of genes and the fetal genotypes of the variants in the GCLC gene interacted with tobacco exposures to increase the risk of CTDs. Our study suggests that the genetic basis underlying susceptibility of the developing heart to the adverse effects of maternal obesity and tobacco use involve both maternal and embryonic genetic variants. These results may provide insights into the underlying pathophysiology of CTDs, and ultimately lead to novel prevention strategies.

Comparative Response of the Hepatic Transcriptomes of Domesticated and Wild Turkey to Aflatoxin B1

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Kent M. Reed

2018-01-01

Full Text Available The food-borne mycotoxin aflatoxin B1 (AFB1 poses a significant risk to poultry, which are highly susceptible to its hepatotoxic effects. Domesticated turkeys (Meleagris gallopavo are especially sensitive, whereas wild turkeys (M. g. silvestris are more resistant. AFB1 toxicity entails bioactivation by hepatic cytochrome P450s to the electrophilic exo-AFB1-8,9-epoxide (AFBO. Domesticated turkeys lack functional hepatic GST-mediated detoxification of AFBO, and this is largely responsible for the differences in resistance between turkey types. This study was designed to characterize transcriptional changes induced in turkey livers by AFB1, and to contrast the response of domesticated (susceptible and wild (more resistant birds. Gene expression responses to AFB1 were examined using RNA-sequencing. Statistically significant differences in gene expression were observed among treatment groups and between turkey types. Expression analysis identified 4621 genes with significant differential expression (DE in AFB1-treated birds compared to controls. Characterization of DE transcripts revealed genes dis-regulated in response to toxic insult with significant association of Phase I and Phase II genes and others important in cellular regulation, modulation of apoptosis, and inflammatory responses. Constitutive expression of GSTA3 was significantly higher in wild birds and was significantly higher in AFB1-treated birds when compared to controls for both genetic groups. This pattern was also observed by qRT-PCR in other wild and domesticated turkey strains. Results of this study emphasize the differential response of these genetically distinct birds, and identify genes and pathways that are differentially altered in aflatoxicosis.

The hepatotoxicity of multi-walled carbon nanotubes in mice

Science.gov (United States)

Ji, Zongfei; Zhang, Danying; Li, Ling; Shen, Xizhong; Deng, Xiaoyong; Dong, Ling; Wu, Minhong; Liu, Yuanfang

2009-11-01

The hepatotoxicity of two types of multi-walled carbon nanotubes (MWCNTs), acid-oxidized MWCNTs (O-MWCNTs) and Tween-80-dispersed MWCNTs (T-MWCNTs), were investigated with Kunming mice exposed to 10 and 60 mg kg-1 by intravenous injection for 15 and 60 d. Compared with the PBS group, the body-weight gain of the mice decreased and the level of total bilirubin and aspartate aminotransferase increased in the MWCNT-exposed group with a significant dose-effect relationship, while tumor necrosis factor alpha level did not show significant statistical change within 60 d. Spotty necrosis, inflammatory cell infiltration in portal region, hepatocyte mitochondria swelling and lysis were observed with a significant dose-effect relationship in the MWCNT groups. Liver damage of the T-MWCNT group was more severe than that of the O-MWCNT group according to the Roenigk classification system. Furthermore, T-MWCNTs induce slight liver oxidative damage in mice at 15 d, which was recovered at 60 d. Part of the gene expressions of mouse liver in the MWCNT groups changed compared to the PBS group, including GPCRs (G protein-coupled receptors), cholesterol biosynthesis, metabolism by cytochrome P450, natural-killer-cell-mediated cytotoxicity, TNF- α, NF-κB signaling pathway, etc. In the P450 pathway, the gene expressions of Gsta2 (down-regulated), Cyp2B19 (up-regulated) and Cyp2C50 (down-regulated) had significant changes in the MWCNT groups. These results show that a high dose of T-MWCNTs can induce hepatic toxicity in mice while O-MWCNTs seem to have less toxicity.

Clonal adaptation of cancer cells in flatfish liver to environmental contamination by changes in expression off P-gp related MXR, CYP450, GST-A and G6PDH activity

NARCIS (Netherlands)

Kohler, A.; Lauritzen, B.; Bahns, S.; George, S. G.; Forlin, L.; van Noorden, C. J. F.

1998-01-01

Progression from eosinophilic foci to persistent basophilic foci and carcinomas was observed in pollution-induced hepatocellular carcinogenesis in European flounder (Platichthys flesus L.) in a similar sequence as in chemically induced liver cancer in mammals. Image analysis was used to quantify

Antioxidant mechanism of black garlic extract involving nuclear factor erythroid 2-like factor 2 pathway.

Science.gov (United States)

Ha, Ae Wha; Kim, Woo Kyoung

2017-06-01

Although studies have revealed that black garlic is a potent antioxidant, its antioxidant mechanism remains unclear. The objective of this study was to determine black garlic's antioxidant activities and possible antioxidant mechanisms related to nuclear factor erythroid 2-like factor 2 (Nrf2)-Keap1 complex. After four weeks of feeding rats with a normal fat diet (NF), a high-fat diet (HF), a high-fat diet with 0.5% black garlic extract (HF+BGE 0.5), a high-fat diet with 1.0% black garlic extract (HF+BGE 1.0), or a high-fat diet with 1.5% black garlic extract (HF+BGE 1.5), plasma concentrations of glucose, insulin,homeostatic model assessment of insulin resistance (HOMA-IR) were determined. As oxidative stress indices, plasma concentrations of thiobarbituric acid reactive substances (TBARS) and 8-isoprostaglandin F2α (8-iso-PGF) were determined. To measure antioxidant capacities, plasma total antioxidant capacity (TAC) and activities of antioxidant enzymes in plasma and liver were determined. The mRNA expression levels of antioxidant related proteins such as Nrf2, NAD(P)H: quinone-oxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1), glutathione reductase (GR), and glutathione S-transferase alpha 2 (GSTA2) were examined. Plasma glucose level, plasma insulin level, and HOMA-IR in black garlic supplemented groups were significantly ( P concentration and TAC in the HF+BGE 1.5 group were significantly decreased compared to those of the HF group. The activities of catalase and glutathione peroxidase were significantly ( P antioxidant systems in rats fed with black garlic extract were related to mRNA expression levels of Nrf2 related genes.

Activation of p62-keap1-Nrf2 antioxidant pathway in the early stage of acetaminophen-induced acute liver injury in mice.

Science.gov (United States)

Shen, Zhenyu; Wang, Yu; Su, Zhenhui; Kou, Ruirui; Xie, Keqin; Song, Fuyong

2018-02-25

Acetaminophen (APAP) overdose can cause severe liver failure even death. Nearly half of drug-induced liver injury is attributed to APAP in the US and many European countries. Oxidative stress has been validated as a critical event involved in APAP-induced liver failure. p62/SQSTM1, a selective autophagy adaptor protein, is reported to regulate Nrf2-ARE antioxidant pathway in response to oxidative stress. However, the exact role of p62-keap1-Nrf2 antioxidant pathway in APAP-induced hepatotoxicity remains unknown. In the present study, the dose-response and time-course model in C57/BL6 mice were established by intraperitoneal injection of APAP. The results of serum alanine/aspartate aminotransferases (ALT/AST) and histological examination demonstrated that APAP overdose resulted in the severe liver injury. In the meantime, the levels of p62, phospho-p62 and nuclear Nrf2 were significantly increased by APAP in mice liver, suggesting an activation of p62-keap1-Nrf2 pathway. In addition, the expression of GSTA1 mRNA was increased in a dose-dependent manner, while the mRNA levels of HO-1 and GCLC were decreased with the increase of APAP dose. Our further investigation found that expression of HO-1 and GCLC peaked at 3 h∼6 h, and then were decreased gradually. Taken together, these results indicated that p62-keap1-Nrf2 antioxidant pathway was primarily activated in the early stage of APAP hepatotoxicity, which might play a protective role in the process of APAP-induced acute liver injury. Copyright © 2018 Elsevier B.V. All rights reserved.

Cranberry juice concentrate does not significantly decrease the incidence of acquired bacteriuria in female hip fracture patients receiving urine catheter: a double-blind randomized trial

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Gunnarsson AK

2017-01-01

Full Text Available Anna-Karin Gunnarsson,1 Lena Gunningberg,2 Sune Larsson,1 Kenneth B Jonsson1 1Institution of Surgical Sciences, Uppsala University, Uppsala, Sweden; 2Institution of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden Background: Urinary tract infection (UTI is a common complication among patients with hip fractures. Receiving an indwelling urinary catheter is a risk factor for developing UTIs. Treatment of symptomatic UTIs with antibiotics is expensive and can result in the development of antimicrobial resistance. Cranberries are thought to prevent UTI. There is no previous research on this potential effect in patients with hip fracture who receive urinary catheters. Aim: The aim of this study is to investigate whether intake of cranberry juice concentrate preoperatively decreases the incidence of postoperative UTIs in hip fracture patients that received a urinary catheter. Design: This study employed a randomized, placebo-controlled double-blind trial. Method: Female patients, aged 60 years and older, with hip fracture (n=227 were randomized to receive cranberry or placebo capsules daily, from admission, until 5 days postoperatively. Urine cultures were obtained at admission, 5 and 14 days postoperatively. In addition, Euro Qual five Dimensions assessments were performed and patients were screened for UTI symptoms. Result: In the intention-to-treat analysis, there was no difference between the groups in the proportion of patients with hospital-acquired postoperative positive urine cultures at any time point. When limiting the analysis to patients that ingested at least 80% of the prescribed capsules, 13 of 33 (39% in the placebo group and 13 of 47 (28% in the cranberry group (P=0.270 had a positive urine culture at 5 days postoperatively. However, this difference was not statistically significant (P=0.270. Conclusion: Cranberry concentrate does not seem to effectively prevent UTIs in female patients with hip fracture and

Prenatal Phthalate Exposures and Anogenital Distance in Swedish Boys

Science.gov (United States)

Carlstedt, Fredrik; Jönsson, Bo AG.; Lindh, Christian H.; Jensen, Tina K.; Bodin, Anna; Jonsson, Carin; Janson, Staffan; Swan, Shanna H.

2014-01-01

Background: Phthalates are used as plasticizers in soft polyvinyl chloride (PVC) and in a large number of consumer products. Because of reported health risks, diisononyl phthalate (DiNP) has been introduced as a replacement for di(2-ethylhexyl) phthalate (DEHP) in soft PVC. This raises concerns because animal data suggest that DiNP may have antiandrogenic properties similar to those of DEHP. The anogenital distance (AGD)—the distance from the anus to the genitals—has been used to assess reproductive toxicity. Objective: The objective of this study was to examine the associations between prenatal phthalate exposure and AGD in Swedish infants. Methods: AGD was measured in 196 boys at 21 months of age, and first-trimester urine was analyzed for 10 phthalate metabolites of DEP (diethyl phthalate), DBP (dibutyl phthalate), DEHP, BBzP (benzylbutyl phthalate), as well as DiNP and creatinine. Data on covariates were collected by questionnaires. Results: The most significant associations were found between the shorter of two AGD measures (anoscrotal distance; AGDas) and DiNP metabolites and strongest for oh-MMeOP [mono-(4-methyl-7-hydroxyloctyl) phthalate] and oxo-MMeOP [mono-(2-ethyl-5-oxohexyl) phthalate]. However, the AGDas reduction was small (4%) in relation to more than an interquartile range increase in DiNP exposure. Conclusions: These findings call into question the safety of substituting DiNP for DEHP in soft PVC, particularly because a shorter male AGD has been shown to relate to male genital birth defects in children and impaired reproductive function in adult males and the fact that human levels of DiNP are increasing globally. Citation: Bornehag CG, Carlstedt F, Jönsson BA, Lindh CH, Jensen TK, Bodin A, Jonsson C, Janson S, Swan SH. 2015. Prenatal phthalate exposures and anogenital distance in Swedish boys. Environ Health Perspect 123:101–107; http://dx.doi.org/10.1289/ehp.1408163 PMID:25353625

Broken Promises? NAFTA, Immigration, and ‘Shadow’ Regionalism Promesses Rompues ? L’ALENA, l’immigration et le régionalisme informel ¿Promesas incumplidas? El TLCAN, la inmigración y el regionalismo informal

Directory of Open Access Journals (Sweden)

Fanny Lauby

2011-08-01

Full Text Available The reduction of immigration was never an official objective of the North American Free Trade Agreement. Yet, it was generally supposed to be one of its long-term consequences. Fifteen years later, Mexican immigration to the United States has in fact increased. The agreement has failed to reduce the attractiveness of the U.S. labor market for Mexican workers and to provide sustainable alternatives to immigration. Over the same period of time, American politicians and the American media have consistently embraced a narrative in which immigration control has become a matter of national security. A paradox has emerged from these two conflicting trends. While the measures taken by the federal government have failed to prevent unauthorized migrants from entering the country, they have also encouraged them to stay longer in the U.S. by making border-crossings too risky. The 1990s therefore witnessed a significant growth of the undocumented population of the United States. This paper analyzes the emergence of a “shadow” regional system between Mexico and the U.S., driven by immigrants themselves, as well as those who profit from undocumented immigration, rather than by institutional actors. This shadow integration is the product of two types of flows: people moving north of the border and, increasingly, remittances moving south. Remittances in turn reinforce immigration trends since they perpetuate the expectations of immigrants. This article examines the development of this parallel form of integration that has taken place at the same time as the implementation of the trade agreement, beyond the control of the Mexican and American governments.La réduction des flux d’immigration n’a jamais été un objectif officiel de l’Accord de Libre Échange Nord Américain. Cependant, elle a souvent été envisagée comme une conséquence à long terme de sa mise en place. Quinze ans plus tard, l’immigration vers les États-Unis en provenance du Mexique s’est en réalité accélérée. L’accord n’a pas pu réduire l’attractivité du marché du travail américain pour les travailleurs mexicains et produire une alternative durable à l’immigration. Au cours de la même période, les hommes politiques et les médias américains ont adopté l’idée selon laquelle le contrôle de l’immigration serait devenu un problème de sécurité nationale. Un paradoxe a émergé de ces deux tendances conflictuelles. Alors que les mesures prises par le gouvernement fédéral n’ont pu prévenir l’afflux d’immigrés sans papiers, elles ont en revanche accru la durée de séjour de ces derniers en accroissant les risques liés à la traversée de la frontière. Dès lors, les années 1990 ont connu une augmentation significative de la population sans papiers des États-Unis. Cet article analyse l’émergence d’un système régional d’intégration entre le Mexique et les États-Unis, impulsé par les immigrés eux-mêmes, ainsi que par ceux qui profitent de l’immigration irrégulière, plutôt que par les acteurs institutionnels. Cette intégration informelle est le produit de deux types de mouvement : celui des migrants vers le nord de la frontière et, de plus en plus, celui de leurs transferts de fonds vers le sud. Ces transferts alimentent à leur tour les flux d’immigration, puisqu’ils perpétuent les attentes des immigrés. Cet article examine le développement de cette forme parallèle d’intégration qui s’est déroulé au même moment que la mise en place de l’accord de libre-échange, au-delà du contrôle des gouvernements mexicain et américain.La reducción de los flujos de inmigración nunca fue un objetivo oficial del Tratado de Libre Comercio de América del Norte. Sin embargo, ha sido considerada, muchas veces, como una consecuencia a largo plazo de la ejecución de dicho tratado. En realidad, quince años después, la inmigración desde México hacia los Estados Unidos ha aumentado. El tratado no ha podido reducir el poder atractivo del mercado laboral norte americano en los trabajadores mejicanos ni proponer tampoco una alternativa sostenible a la inmigración. Durante el mismo periodo, los hombres políticos y los medios de comunicación norteamericanos adoptaron la idea según la cual la inmigración se hubiera convertido en un problema de seguridad nacional. Una paradoja surgió de estas dos tendencias conflictuales. No sólo las medidas que tomó el gobierno federal no pudieron prevenir la afluencia de inmigrantes indocumentados, sino que también aumentaron a la vez la duración de su estancia fuera del país y los riesgos de la travesía de la frontera. Por consiguiente hubo, en los años 1990, un aumento significativo de la población indocumentada en los Estados Unidos.Este artículo analiza la emergencia de un sistema regional de integración informal entre México y los Estados Unidos, movido por los mismos inmigrantes, así como por los que sacan provecho de la inmigración irregular, y no por los protagonistas institucionales. Esta integración informal es el resultado de dos tipos de movimientos: el de los migrantes hacia el norte de la frontera y, cada vez más, el de las remesas hacia el sur. Estas remesas alimentan también los flujos de inmigración, puesto que perpetúan las expectativas de los inmigrantes.  Este artículo examina el desarrollo de esta forma paralela de integración que apareció con la ejecución del tratado de libre comercio, fuera del control de los gobiernos mexicano y norteamericano.

Short-term calorie restriction feminizes the mRNA profiles of drug metabolizing enzymes and transporters in livers of mice.

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Fu, Zidong Donna; Klaassen, Curtis D

2014-01-01

Calorie restriction (CR) is one of the most effective anti-aging interventions in mammals. A modern theory suggests that aging results from a decline in detoxification capabilities and thus accumulation of damaged macromolecules. The present study aimed to determine how short-term CR alters mRNA profiles of genes that encode metabolism and detoxification machinery in the liver. Male C57BL/6 mice were fed CR (0, 15, 30, or 40%) diets for one month, followed by mRNA quantification of 98 xenobiotic processing genes (XPGs) in the liver, including 7 uptake transporters, 39 phase-I enzymes, 37 phase-II enzymes, 10 efflux transporters, and 5 transcription factors. In general, 15% CR did not alter mRNAs of most XPGs, whereas 30 and 40% CR altered over half of the XPGs (32 increased and 29 decreased). CR up-regulated some phase-I enzymes (fold increase), such as Cyp4a14 (12), Por (2.3), Nqo1 (1.4), Fmo2 (5.4), and Fmo3 (346), and numerous number of phase-II enzymes, such as Sult1a1 (1.2), Sult1d1 (2.0), Sult1e1 (33), Sult3a1 (2.2), Gsta4 (1.3), Gstm2 (1.3), Gstm3 (1.7), and Mgst3 (2.2). CR feminized the mRNA profiles of 32 XPGs in livers of male mice. For instance, CR decreased the male-predominantly expressed Oatp1a1 (97%) and increased the female-predominantly expressed Oatp1a4 (11). In conclusion, short-term CR alters the mRNA levels of over half of the 98 XPGs quantified in livers of male mice, and over half of these alterations appear to be due to feminization of the liver. Copyright © 2013 Elsevier Inc. All rights reserved.

The presence of carbon nanostructures in bakery products induces metabolic stress in human mesenchymal stem cells through CYP1A and p53 gene expression.

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Al-Hadi, Ahmed M; Periasamy, Vaiyapuri Subbarayan; Athinarayanan, Jegan; Alshatwi, Ali A

2016-01-01

Ingredients commonly present in processed foods are excellent substrates for chemical reactions during modern thermal cooking or processing, which could possibly result in deteriorative carbonization changes mediated by a variety of thermal reactions. Spontaneous self-assembling complexation or polymerization of partially combusted lipids, proteins, and other food macromolecules with synthetic food additives during high temperature food processing or baking (200-250 °C) would result in the formation of carbon nanostructures (CNs). These unknown nanostructures may produce adverse physiological effects or potential health risks. The present work aimed to identify and characterize the nanostructures from the crusts of bread. Furthermore, a toxicological risk assessment of these nanostructures was conducted using human mesenchymal stem cells (hMSCs) as a model for cellular uptake and metabolic oxidative stress, with special reference to induced adipogenesis. CNs isolated from bread crusts were characterized using transmission electron microscopy. The in vitro risk assessment of the CNs was carried out in hMSCs using an MTT assay, cell morphological assessment, a reactive oxygen species assay, a mitochondrial trans-membrane potential assay, cell cycle progression assessment and gene expression analysis. Our results revealed that bread crusts contain CNs, which may form during the bread-making process. The in vitro results indicate that carbon nanostructures have moderately toxic effects in the hMSCs at a high dose (400 μg/mL). The mitochondrial trans-membrane potentials and intracellular ROS levels of the hMSCs were altered at this dose. The levels of the mRNA transcripts of metabolic stress-responsive genes such as CAT, GSR, GSTA4, CYP1A and p53 were significantly altered in response to CNs. Copyright © 2015 Elsevier B.V. All rights reserved.

Grapefruit juice intake does not enhance but rather protects against aflatoxin B1-induced liver DNA damage through a reduction in hepatic CYP3A activity.

Science.gov (United States)

Miyata, Masaaki; Takano, Hiroki; Guo, Lian Q; Nagata, Kiyoshi; Yamazoe, Yasushi

2004-02-01

Influence of grapefruit juice intake on aflatoxin B1 (AFB1)-induced liver DNA damage was examined using a Comet assay in F344 rats given 5 mg/kg AFB1 by gavage. Rats allowed free access to grapefruit juice for 5 days prior to AFB1 administration resulted in clearly reduced DNA damage in liver, to 65% of the level in rats that did not receive grapefruit juice. Furthermore, rats treated with grapefruit juice extract (100 mg/kg per os) for 5 days prior to AFB1 treatment also reduced the DNA damage to 74% of the level in rats that did not receive grapefruit juice. No significant differences in the portal blood and liver concentrations of AFB1 were observed between grapefruit juice intake rats and the controls. In an Ames assay with AFB1 using Salmonella typhimurium TA98, lower numbers of revertant colonies were detected with hepatic microsomes prepared from rats administered grapefruit juice, compared with those from control rats. Microsomal testosterone 6beta-hydroxylation was also lower with rats given grapefruit juice than with control rats. Immunoblot analyses showed a significant decrease in hepatic CYP3A content, but not CYP1A and CYP2C content, in microsomes of grapefruit juice-treated rats than in non-treated rats. No significant difference in hepatic glutathione S-transferase (GST) activity and glutathione content was observed in the two groups. GSTA5 protein was not detected in hepatic cytosol of the two groups. In microsomal systems, grapefruit juice extract inhibited AFB1-induced mutagenesis in the presence of a microsomal activation system from livers of humans as well as rats. These results suggest that grapefruit juice intake suppresses AFB1-induced liver DNA damage through inactivation of the metabolic activation potency for AFB1 in rat liver.

Effect of dietary restriction and subsequent re-alimentation on the transcriptional profile of bovine jejunal epithelium.

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Keogh, Kate; Waters, Sinead M; Cormican, Paul; Kelly, Alan K; Kenny, David A

2018-01-01

Compensatory growth (CG), an accelerated growth phenomenon which occurs following a period of dietary restriction is utilised worldwide in animal production systems as a management practise to lower feed costs. The objective of this study was to evaluate the contribution of jejunal epithelial to CG in cattle through transcriptional profiling following a period of dietary restriction as well as subsequent re-alimentation induced CG. Sixty Holstein Friesian bulls were separated into two groups; RES and ADLIB, with 30 animals in each. RES animals were offered a restricted diet for 125 days (Period 1) followed by ad libitum feeding for 55 days (Period 2). ADLIB animals had ad libitum access to feed across both periods 1 and 2. At the end of each period, 15 animals from each treatment group were slaughtered, jejunal epithelium collected and RNAseq analysis performed. Animals that were previously diet restricted underwent CG, gaining 1.8 times the rate of their non-restricted counterparts. Twenty-four genes were differentially expressed in RES compared to ADLIB animals at the end of Period 1, with only one gene, GSTA1, differentially expressed between the two groups at the end of Period 2. When analysed within treatment (RES, Period 2 v Period 1), 31 genes were differentially expressed between diet restricted and animals undergoing CG. Dietary restriction and subsequent re-alimentation were associated with altered expression of genes involved in digestion and metabolism as well as those involved in cellular division and growth. Compensatory growth was also associated with greater expression of genes involved in cellular protection and detoxification in jejunal epithelium. This study highlights some of the molecular mechanisms regulating the response to dietary restriction and subsequent re-alimentation induced CG in cattle; however the gene expression results suggest that most of the CG in jejunal epithelium had occurred by day 55 of re-alimentation.

Performance of a novel keratinocyte-based reporter cell line to screen skin sensitizers in vitro

International Nuclear Information System (INIS)

Emter, Roger; Ellis, Graham; Natsch, Andreas

2010-01-01

In vitro tests are needed to replace animal tests to screen for the skin sensitization potential of chemicals. Skin sensitizers are electrophilic molecules and the Nrf2-electrophile-sensing pathway comprising the repressor protein Keap1, the transcription factor Nrf2 and the antioxidant response element (ARE) is emerging as a toxicity pathway induced by skin sensitizers. Previously, we screened a large set of chemicals in the reporter cell line AREc32, which contains an eight-fold repeat of the rat GSTA2 ARE-sequence upstream of a luciferase reporter gene in the human breast cancer cell line MCF7. This approach was now further developed to bring it closer to the conditions in the human skin and to propose a fully standardized assay. To this end, a luciferase reporter gene under control of a single copy of the ARE-element of the human AKR1C2 gene was stably inserted into HaCaT keratinocytes. A standard operating procedure was developed whereby chemicals are routinely tested at 12 concentrations in triplicate for significant induction of gene activity. We report results from this novel assay on (i) a list of reference chemicals published by ECVAM, (ii) the ICCVAM list of chemicals for validation of alternative endpoints in the LLNA and (iii) on a more general list of 67 chemicals derived from the ICCVAM database. For comparison, peptide reactivity data are presented for the same chemicals. The results indicate a good predictive value of this approach for hazard identification. Its technical simplicity, the high-throughput format and the good predictivity may make this assay a candidate for rapid validation to meet the tight deadline to replace animal tests for skin sensitization by 2013 set by the European authorities.

Presence of nanosilica (E551) in commercial food products: TNF-mediated oxidative stress and altered cell cycle progression in human lung fibroblast cells.

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Athinarayanan, Jegan; Periasamy, Vaiyapuri Subbarayan; Alsaif, Mohammed A; Al-Warthan, Abdulrahman A; Alshatwi, Ali A

2014-04-01

Silica (E551) is commonly used as an anti-caking agent in food products. The morphology and the dimension of the added silica particles are not, however, usually stated on the food product label. The food industry has adapted nanotechnology using engineered nanoparticles to improve the quality of their products. However, there has been increased debate regarding the health and safety concerns related to the use of engineered nanoparticles in consumer products. In this study, we investigated the morphology and dimensions of silica (E551) particles in food. The silica content of commercial food products was determined using inductively coupled plasma optical emission spectrometry. The result indicates that 2.74-14. 45 μg/g silica was found in commercial food products; however, the daily dietary intake in increase causes adverse effects on human health. E551 was isolated from food products and the morphology, particle size, crystalline nature, and purity of the silica particles were analyzed using XRD, FTIR, TEM, EDX and DLS. The results of these analyses confirmed the presence of spherical silica nanoparticles (of amorphous nature) in food, approximately 10-50 nm in size. The effects of E551 on human lung fibroblast cell viability, intracellular ROS levels, cell cycle phase, and the expression levels of metabolic stress-responsive genes (CAT, GSTA4, TNF, CYP1A, POR, SOD1, GSTM3, GPX1, and GSR1) were studied. The results suggest that E551 induces a dose-dependent cytotoxicity and changes in ROS levels and alters the gene expression and cell cycle. Treatment with a high concentration of E551 caused significant cytotoxic effects on WI-38 cells. These findings have implications for the use of these nanoparticles in the food industry.

Evaluation of 309 environmental chemicals using a mouse embryonic stem cell adherent cell differentiation and cytotoxicity assay.

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Kelly J Chandler

Full Text Available The vast landscape of environmental chemicals has motivated the need for alternative methods to traditional whole-animal bioassays in toxicity testing. Embryonic stem (ES cells provide an in vitro model of embryonic development and an alternative method for assessing developmental toxicity. Here, we evaluated 309 environmental chemicals, mostly food-use pesticides, from the ToxCast™ chemical library using a mouse ES cell platform. ES cells were cultured in the absence of pluripotency factors to promote spontaneous differentiation and in the presence of DMSO-solubilized chemicals at different concentrations to test the effects of exposure on differentiation and cytotoxicity. Cardiomyocyte differentiation (α,β myosin heavy chain; MYH6/MYH7 and cytotoxicity (DRAQ5™/Sapphire700™ were measured by In-Cell Western™ analysis. Half-maximal activity concentration (AC₅₀ values for differentiation and cytotoxicity endpoints were determined, with 18% of the chemical library showing significant activity on either endpoint. Mining these effects against the ToxCast Phase I assays (∼500 revealed significant associations for a subset of chemicals (26 that perturbed transcription-based activities and impaired ES cell differentiation. Increased transcriptional activity of several critical developmental genes including BMPR2, PAX6 and OCT1 were strongly associated with decreased ES cell differentiation. Multiple genes involved in reactive oxygen species signaling pathways (NRF2, ABCG2, GSTA2, HIF1A were strongly associated with decreased ES cell differentiation as well. A multivariate model built from these data revealed alterations in ABCG2 transporter was a strong predictor of impaired ES cell differentiation. Taken together, these results provide an initial characterization of metabolic and regulatory pathways by which some environmental chemicals may act to disrupt ES cell growth and differentiation.

Cytoprotective role of the fatty acid binding protein 4 against oxidative and endoplasmic reticulum stress in 3T3-L1 adipocytes

Directory of Open Access Journals (Sweden)

Kazuaki Kajimoto

2014-01-01

Full Text Available The fatty acid binding protein 4 (FABP4, one of the most abundant proteins in adipocytes, has been reported to have a proinflammatory function in macrophages. However, the physiological role of FABP4, which is constitutively expressed in adipocytes, has not been fully elucidated. Previously, we demonstrated that FABP4 was involved in the regulation of interleukin-6 (IL-6 and vascular endothelial growth factor (VEGF production in 3T3-L1 adipocytes. In this study, we examined the effects of FABP4 silencing on the oxidative and endoplasmic reticulum (ER stress in 3T3-L1 adipocytes. We found that the cellular reactive oxygen species (ROS and 8-nitro-cyclic GMP levels were significantly elevated in the differentiated 3T3-L1 adipocytes transfected with a small interfering RNA (siRNA against Fabp4, although the intracellular levels or enzyme activities of antioxidants including reduced glutathione (GSH, superoxide dismutase (SOD and glutathione S-transferase A4 (GSTA4 were not altered. An in vitro evaluation using the recombinant protein revealed that FABP4 itself functions as a scavenger protein against hydrogen peroxide (H2O2. FABP4-knockdown resulted in a significant lowering of cell viability of 3T3-L1 adipocytes against H2O2 treatment. Moreover, four kinds of markers related to the ER stress response including the endoplasmic reticulum to nucleus signaling 1 (Ern1, the signal sequence receptor α (Ssr1, the ORM1-like 3 (Ormdl3, and the spliced X-box binding protein 1 (Xbp1s, were all elevated as the result of the knockdown of FABP4. Consequently, FABP4 might have a new role as an antioxidant protein against H2O2 and contribute to cytoprotection against oxidative and ER stress in adipocytes.

Construction of a subtractive library from hexavalent chromium treated winter flounder (Pseudopleuronectes americanus) reveals alterations in non-selenium glutathione peroxidases

International Nuclear Information System (INIS)

Chapman, Laura M.; Roling, Jonathan A.; Bingham, Lacey K.; Herald, Matt R.; Baldwin, William S.

2004-01-01

Chromium is released during several industrial processes and has accumulated in some estuarine areas. Its effects on mammals have been widely studied, but relatively little information is available on its effects on fish. Gene expression changes are useful biomarkers that can provide information about toxicant exposure and effects, as well as the health of an organism and its ability to adapt to its surroundings. Therefore, we investigated the effects of Cr(VI) on gene expression in the sediment dwelling fish, winter flounder (Pseudopleuronectes americanus). Winter flounder ranging from 300 to 360 g were injected i.p. with Cr(VI) as chromium oxide at 25 μg/kg chromium in 0.15N KCl. Twenty-four hours following injections, winter flounder were euthanized with MS-222 and the livers were excised. Half of the livers were used to make cytosol and the other half were used to isolate mRNA for subtractive hybridization. Subtractive clones obtained were spotted onto nylon filters, which revealed several genes with potentially altered expression due to Cr(VI), including an α class GST, 1-Cys peroxiredoxin (a non-selenium glutathione peroxidase), a P-450 2X subfamily member, two elongation factors (EF-1 gamma and EF-2), and complement component C3. Semi-quantitative RT-PCR was performed and confirmed that Cr(VI) down-regulated complement component C3, an EST, and two potential glutathione peroxidases, GSTA3 and 1-Cys peroxiredoxin. In addition, cytosolic GSH peroxidase activity was reduced, and silver stained SDS-PAGE gels from glutathione-affinity purified cytosol demonstrated that a 27.1 kDa GSH-binding protein was down-regulated greater than 50%. Taken together, Cr(VI) significantly altered the expression of several genes including two potential glutathione peroxidases in winter flounder

Slides with no attached paper

International Nuclear Information System (INIS)

Warin, Dominique; Wallenius, Janne; Ouzounian, Gerald; Wikberg, Peter; Todd, Terry A.; Kormilitsyn, Mikhael V.; Osipenko, Alexander G.; Mayorshin, A.A.; McLachlan, Fiona; Nash, Ken L.; Nilsson, M.; Grimes, T.; Braley, J.C.; TAKESHITA, Kenji; Babain, Vasiliy A.; Spendlikova, I.; Distler, P.; John, J.; Sebesta, F.; VU, Trong-Hung; SIMONIN, Jean-Pierre; PAULENOVA, Alena; PRECEK, Martin; HARTIG, Kyle; KNAPP, Nathan; Vidick, Geoffrey; Bouslimani, Nouri; Desreux, Jean F.; Lewis, F.W.; Hudson, M.J.; Harwood, L.M.; Nunez, Ana; Nagarajan, K.; Vasudeva Rao, P.R.; Raj, Baldev; Ignatiev, Victor; Surenkov, Alexander; Pouchon, Manuel A.; Skarnemark, Gunnar; Allard, Stefan; Ekberg, Christian; Retegan, Teodora; Nordlund, Anders; John, Jan; Maershin, Alexander; Zakirov, R.; Panov, A.; Toropov, Andrey

2010-01-01

This document brings together the different presentations (slides) given at the workshop but with no attached paper. These slides refer to the following presentations: - Presentation of ITN (Instituto Tecnologico e Nuclear); - Minor Actinide Partitioning (Dominique Warin); - Transmutation (Janne Wallenius); - Radioactive Waste Management, IGD-TP (Gerald Ouzounian); - Present status of the Swedish nuclear waste management programme (Peter Wikberg); - The U.S. Fuel Cycle Research and Development Program - Separations Research and Development (Terry Todd); - Strategies and national programs of closed fuel cycles - Russian Expert Vision (Mikhael Kormilitsyn) - Extraction Studies Of Potential Solvent Formulations For The GANEX Process (Fiona MacLachlan); - Investigations of The Fundamental Chemistry of the TALSPEAK Process (Ken Nash); - Extraction Separation of Trivalent Minor Actinides and Lanthanides by Hexa-dentate Nitrogen-donor Extractant, TPEN, and its Analogs (Kenji Takeshita); - Fluorinated Diluents for HLW Processing - technological point of view (Vasiliy Babain); - Extraction properties of some new pyridine molecules and search for better diluents (Irena Spendlikova); - Kinetics of extraction of Eu 3+ ion by TODGA and CyMe 4 -BTBP studied using the RMC technique (Trong Hung Vu); - Redox Chemistry of Neptunium in Solutions of Nitric Acid (Alena Paulenova); - NMR applied to actinide ions and their complexes. In search of covalency effects (Geoffrey Vidick); - Towards 'Stability Rules' for Radiolysis of bis-DGA compounds (Ana Nunez); - Pyroprocess Research Activities at IGCAR, Kalpakkam, India (K. Nagarajan); - Critical issues of nuclear energy systems employing molten salt fluorides: from ISTC No. 1606 to No. 3749 (1. year of project activity) and MARS/EVOL cooperation (Victor Ignatiev); - Conversion processes: Internal Gelation and the Sphere-pac concept (Manuel Pouchon); - A Combined Nuclear Technology and Nuclear Chemistry Master. A Unique

An analysis of fat-related and fiber-related behavior in men and women with type 2 diabetes mellitus: key findings for clinical practice

Directory of Open Access Journals (Sweden)

Hendrychova T

2013-09-01

Full Text Available Tereza Hendrychova,1 Magda Vytrisalova,1 Jiri Vlcek,1 Alena Smahelova,2 Ales Antonin Kubena1 1Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Czech Republic; 2Diabetology Centre, Department of Gerontology and Metabolism, University Hospital and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Czech Republic Background: Despite the efforts of health care providers, adherence of patients with type 2 diabetes to the recommended diet is poor. The aim of this study was to describe the eating habits with emphasis on fat and fiber-related behavior (FFB as well as the relationship between FFB behavior and parameters of diabetes control in men and women with type 2 diabetes mellitus. Methods: The subjects in this observational cross-sectional study were 200 patients (54.5% male, mean age 66.2 ± 10.1 years, mean Diabetes Control and Complications Trial [DDCT] glycosylated hemoglobin [HbA1c] 7.6% ± 1.7% recruited from diabetes outpatient clinics in the Czech Republic. The subjects filled out the Fat- and Fiber-related Diet Behavior Questionnaire. The most recent patient data on diabetes control and drug therapy were derived from patient medical records. Results: Patients tend to modify the dishes they are used to, rather than remove them completely from their diet and replace them by other types of foods. It is easier to perform healthier fat-related behaviors than fiber-related ones. Women scored significantly better than men on the fat-related diet habits summary scale (P = 0.002, as well as on "modify meat" (P = 0.001 and "substitute specially manufactured low-fat foods" (P = 0.045 subscales. A better score on the fat-related diet habits summary scale was significantly associated with higher HbA1c (ρ = -0.248; P = 0.027 and higher waist circumference (ρ = -0.254; P = 0.024 in women. Conclusion: Type 2 diabetes patients are likely to vary in their FFB behavior, and

Fat- and fiber-related diet behavior among type 2 diabetes patients from distinct regions

Directory of Open Access Journals (Sweden)

Hendrychova T

2015-02-01

Full Text Available Tereza Hendrychova,1 Magda Vytrisalova,1 Abdullah Alwarafi,2 Jurjen Duintjer Tebbens,3,4 Helena Vankatova,1 Sandra Leal,5 Ales Antonin Kubena,1 Alena Smahelova,6 Jiri Vlcek1 1Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Hradec Králové, Czech Republic; 2Faculty of Dentistry, Ibb University, Ibb, Yemen; 3Department of Biophysics and Physical Chemics, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Hradec Králové, Czech Republic; 4Institute of Computer Science, Academy of Sciences of the Czech Republic, Prague, Czech Republic; 5Department of Clinical Pharmacy, El Rio Community Health Center, Tucson, AZ, USA; 6Diabetes Center, Department of Gerontology and Metabolism, University Hospital and Faculty of Medicine in Hradec Králové, Charles University in Prague, Hradec Králové, Czech Republic Purpose: Diet and eating habits are of key importance in patients with type 2 diabetes mellitus (T2DM. The purpose of this comparative study was to analyze fat- and fiber-related behavior (FFB in patients with T2DM from distinct cultural areas. Patients and methods: Observational study was carried out in the Czech Republic (CR (n=200, the US (n=207, and Yemen (n=200. Patients completed the Fat- and Fiber-related Diet Behavior Questionnaire (FFBQ. Results: Differences in all aspects of FFB among countries were found (P<0.05. The best fat-related behavior reported was from patients from the CR. Patients from the US showed the worst fat-related behavior in total. On the other hand, patients from the US reported the best fiber-related behavior. Patients from Yemen reached the worst scores in all fat-related domains. Patients from all studied countries reported the best results in the “modify meat” and “avoid fat as flavoring” and the worst in the “substitute high fiber” subscales. Conclusion: Professionals involved in the diet education of T2DM patients

Adherence in adults with type 1 diabetes mellitus correlates with treatment satisfaction but not with adverse events

Directory of Open Access Journals (Sweden)

Hendrychova T

2013-09-01

Full Text Available Tereza Hendrychova,1 Magda Vytrisalova,1 Alena Smahelova,2 Jiri Vlcek,1 Ales Antonin Kubena1 1Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Hradec Králové, Czech Republic; 2Diabetes Center, Department of Gerontology and Metabolism, University Hospital and Faculty of Medicine in Hradec Králové, Charles University in Prague, Hradec Králové, Czech Republic Purpose: Diabetes self-care and self-monitoring adherence has a positive effect on the metabolic control of the disease. The aim of this study was to analyze the adherence to self-care recommendations and to identify its correlates in adults with type 1 diabetes mellitus. Patients and methods: One hundred and eleven patients with type 1 diabetes were enrolled in an observational cross-sectional study conducted at the Diabetes Center of the University Hospital in Hradec Králové, Czech Republic. Diabetes self-care adherence was measured by the Self Care Inventory-Revised, and treatment satisfaction by the Diabetes Treatment Satisfaction Questionnaire-status version. Additional data were collected from self-administered questionnaires and medical records. The Mann–Whitney test, Spearman correlations, and multiple linear regressions were used in the statistical analysis. Results: The mean age of patients was 42.4 years; 59.5% of them were females and 53.2% of all patients used an insulin pump. The mean glycosylated hemoglobin (HbA1c was 66.2 ± 15.3 mmol/mol and the mean insulin dosage was 0.6 ± 0.3 IU insulin/kg/day. The number of hypoglycemic episodes (including severe that patients had in the last month before taking the survey was 3.6 ± 3.2. Self-care adherence was associated with treatment satisfaction (0.495; P = 0.004 along with frequency of self-monitoring of before meal blood glucose (0.267; P = 0.003. It was not associated with the incidence of hypoglycemic events or any other insulin therapy-related problems

Targeting myeloid-derived suppressor cells augments antitumor activity against lung cancer

Directory of Open Access Journals (Sweden)

Srivastava MK

2012-10-01

Full Text Available Minu K Srivastava,1,2 Li Zhu,1,2 Marni Harris-White,2 Min Huang,1–3 Maie St John,1,3 Jay M Lee,1,3 Ravi Salgia,4 Robert B Cameron,1,3,5 Robert Strieter,6 Steven Dubinett,1–3 Sherven Sharma1–31Department of Medicine, UCLA Lung Cancer Research Program, David Geffen School of Medicine at UCLA, Los Angeles, CA, 2Molecular Gene Medicine Laboratory, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, 3Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, 4Department of Medicine, University of Chicago, Chicago, IL, 5Department of Surgery, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, 6Department of Medicine, University of Virginia, Charlottesville, VA, USAAbstract: Lung cancer evades host immune surveillance by dysregulating inflammation. Tumors and their surrounding stromata produce growth factors, cytokines, and chemokines that recruit, expand, and/or activate myeloid-derived suppressor cells (MDSCs. MDSCs regulate immune responses and are frequently found in malignancy. In this review the authors discuss tumor-MDSC interactions that suppress host antitumor activities and the authors' recent findings regarding MDSC depletion that led to improved therapeutic vaccination responses against lung cancer. Despite the identification of a repertoire of tumor antigens, hurdles persist for immune-based anticancer therapies. It is likely that combined therapies that address the multiple immune deficits in cancer patients will be required for effective therapy. MDSCs play a major role in the suppression of T-cell activation and they sustain tumor growth, proliferation, and metastases. Regulation of MDSC recruitment, differentiation or expansion, and inhibition of the MDSC suppressive function with pharmacologic agents will be useful in the control of cancer growth and progression. Pharmacologic agents that regulate MDSCs may be more effective when combined with

Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis

Directory of Open Access Journals (Sweden)

Cuffari C

2016-02-01

Full Text Available Carmen Cuffari,1 David Pierce,2 Bartosz Korczowski,3 Krzysztof Fyderek,4 Heather Van Heusen,5 Stuart Hossack,6 Hong Wan,5 Alena YZ Edwards,7 Patrick Martin5 1Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Shire, Basingstoke, UK; 3Medical College, University of Rzeszów, Rzeszów, Poland; 4University Children’s Hospital of Cracow, Cracow, Poland; 5Shire, Wayne, PA, USA; 6Covance Clinical Research Unit Limited, Leeds, UK; 7ICON Early Phase Services, Marlow, Buckinghamshire, UK Background: Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA use in pediatric ulcerative colitis (UC.Aim: To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC.Methods: Participants (5–17 years of age; 18–82 kg, stratified by weight with UC received multimatrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day for 7 days. Blood samples were collected pre-dose on days 5 and 6. On days 7 and 8, blood and urine samples were collected and safety was evaluated. 5-ASA and Ac-5-ASA plasma and urine concentrations were analyzed by non-compartmental methods and used to develop a population pharmacokinetic model.Results: Fifty-two subjects (21 [30 mg/kg]; 22 [60 mg/kg]; 9 [100 mg/kg] were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose-proportional increase between 30 and 60 mg/kg/day cohorts. For 30, 60, and 100 mg/kg/day doses, mean percentages of 5-ASA absorbed were 29.4%, 27.0%, and 22.1%, respectively. Simulated steady-state exposures and variabilities for 5-ASA and Ac-5-ASA (coefficient of variation approximately 50% and 40%–45%, respectively were similar to those observed previously in adults at comparable doses. Treatment-emergent adverse events were

Interference with Activator Protein-2 transcription factors leads to induction of apoptosis and an increase in chemo- and radiation- sensitivity in breast cancer cells

LENUS (Irish Health Repository)

Thewes, Verena

2010-05-11

Abstract Background Activator Protein-2 (AP-2) transcription factors are critically involved in a variety of fundamental cellular processes such as proliferation, differentiation and apoptosis and have also been implicated in carcinogenesis. Expression of the family members AP-2α and AP-2γ is particularly well documented in malignancies of the female breast. Despite increasing evaluation of single AP-2 isoforms in mammary tumors the functional role of concerted expression of multiple AP-2 isoforms in breast cancer remains to be elucidated. AP-2 proteins can form homo- or heterodimers, and there is growing evidence that the net effect whether a cell will proliferate, undergo apoptosis or differentiate is partly dependent on the balance between different AP-2 isoforms. Methods We simultaneously interfered with all AP-2 isoforms expressed in ErbB-2-positive murine N202.1A breast cancer cells by conditionally over-expressing a dominant-negative AP-2 mutant. Results We show that interference with AP-2 protein function lead to reduced cell number, induced apoptosis and increased chemo- and radiation-sensitivity. Analysis of global gene expression changes upon interference with AP-2 proteins identified 139 modulated genes (90 up-regulated, 49 down-regulated) compared with control cells. Gene Ontology (GO) investigations for these genes revealed Cell Death and Cell Adhesion and Migration as the main functional categories including 25 and 12 genes, respectively. By using information obtained from Ingenuity Pathway Analysis Systems we were able to present proven or potential connections between AP-2 regulated genes involved in cell death and response to chemo- and radiation therapy, (i.e. Ctgf, Nrp1, Tnfaip3, Gsta3) and AP-2 and other main apoptosis players and to create a unique network. Conclusions Expression of AP-2 transcription factors in breast cancer cells supports proliferation and contributes to chemo- and radiation-resistance of tumor cells by impairing the

Integrating multi-disciplinary field and laboratory methods to investigate the response and recovery of beach-dune systems in Ireland to extreme events

Science.gov (United States)

Farrell, E.; Lynch, K.; Wilkes Orozco, S.; Castro Camba, G.; Scullion, A.

2017-12-01

This two year field monitoring project examines the response and recovery of 1.2km of a coastal beach-dune system in the west coast of Ireland (The Maharees, Brandon Bay, Co. Kerry) to storms. The results from this project initiated a larger scale study to assess the long term evolution of Brandon Bay (12km) and patterns of meso-scale rotation. On a bay scale historic shoreline analyses were completed using historic Ordnance Survey maps, aerial photography, and DGPS surveys inputted to the Digital Shoreline Analysis System. These were coupled with a GSTA-wavemeter experiment that collected 410 sediment samples along the beach and nearshore to identify preferred sediment transport pathways along the bay. On a local scale (1.2km) geomorphological changes of the beach and nearshore were monitored using repeated monthly DGPS surveys and drone technology. Topographical data were correlated with atmospheric data obtained from a locally installed automatic weather station, oceanographic data from secondary sources, and photogrammetry using a camera installed at the site collecting pictures every 10 minutes during daylight hours. Changes in surface elevation landward of the foredune from aeolian processes were measured using five pin transects across the dune. The contribution of local blowout dynamics were measured using drone imagery and structure-from-motion technology. The results establish that the average shoreline recession along the 1.2 km site is 72 m during the past 115 years. The topographic surveys illustrate that natural beach building processes initiate system recovery post storms including elevated foreshores and backshores and nearshore sand bar migration across the entire 1.2 km stretch of coastline. In parallel with the scientific work, the local community have mobilized and are working closely with the lead scientists to implement short term coastal management strategies such as signage, information booklets, sand trap fencing, walkways, wooden

Effects of naturally occurring coumarins on hepatic drug-metabolizing enzymes inmice

International Nuclear Information System (INIS)

Kleiner, Heather E.; Xia, Xiaojun; Sonoda, Junichiro; Zhang, Jun; Pontius, Elizabeth; Abey, Jane; Evans, Ronald M.; Moore, David D.; DiGiovanni, John

2008-01-01

Cytochromes P450 (P450s) and glutathione S-transferases (GSTs) constitute two important enzyme families involved in carcinogen metabolism. Generally, P450s play activation or detoxifying roles while GSTs act primarily as detoxifying enzymes. We previously demonstrated that oral administration of the linear furanocoumarins, isopimpinellin and imperatorin, modulated P450 and GST activities in various tissues of mice. The purpose of the present study was to compare a broader range of naturally occurring coumarins (simple coumarins, and furanocoumarins of the linear and angular type) for their abilities to modulate hepatic drug-metabolizing enzymes when administered orally to mice. We now report that all of the different coumarins tested (coumarin, limettin, auraptene, angelicin, bergamottin, imperatorin and isopimpinellin) induced hepatic GST activities, whereas the linear furanocoumarins possessed the greatest abilities to induce hepatic P450 activities, in particular P450 2B and 3A. In both cases, this corresponded to an increase in protein expression of the enzymes. Induction of P4502B10, 3A11, and 2C9 by xenobiotics often is a result of activation of the pregnane X receptor (PXR) and/or constitutive androstane receptor (CAR). Using a pregnane X receptor reporter system, our results demonstrated that isopimpinellin activated both PXR and its human ortholog SXR by recruiting coactivator SRC-1 in transfected cells. In CAR transfection assays, isopimpinellin counteracted the inhibitory effect of androstanol on full-length mCAR, a Gal4-mCAR ligand-binding domain fusion, and restored coactivator binding. Orally administered isopimpinellin induced hepatic mRNA expression of Cyp2b10, Cyp3a11, and GSTa in CAR(+/+) wild-type mice. In contrast, the induction of Cyp2b10 mRNA by isopimpinellin was attenuated in the CAR(-/-) mice, suggesting that isopimpinellin induces Cyp2b10 via the CAR receptor. Overall, the current data indicate that naturally occurring coumarins have

Short-term calorie restriction feminizes the mRNA profiles of drug metabolizing enzymes and transporters in livers of mice

International Nuclear Information System (INIS)

Fu, Zidong Donna; Klaassen, Curtis D.

2014-01-01

Calorie restriction (CR) is one of the most effective anti-aging interventions in mammals. A modern theory suggests that aging results from a decline in detoxification capabilities and thus accumulation of damaged macromolecules. The present study aimed to determine how short-term CR alters mRNA profiles of genes that encode metabolism and detoxification machinery in the liver. Male C57BL/6 mice were fed CR (0, 15, 30, or 40%) diets for one month, followed by mRNA quantification of 98 xenobiotic processing genes (XPGs) in the liver, including 7 uptake transporters, 39 phase-I enzymes, 37 phase-II enzymes, 10 efflux transporters, and 5 transcription factors. In general, 15% CR did not alter mRNAs of most XPGs, whereas 30 and 40% CR altered over half of the XPGs (32 increased and 29 decreased). CR up-regulated some phase-I enzymes (fold increase), such as Cyp4a14 (12), Por (2.3), Nqo1 (1.4), Fmo2 (5.4), and Fmo3 (346), and numerous number of phase-II enzymes, such as Sult1a1 (1.2), Sult1d1 (2.0), Sult1e1 (33), Sult3a1 (2.2), Gsta4 (1.3), Gstm2 (1.3), Gstm3 (1.7), and Mgst3 (2.2). CR feminized the mRNA profiles of 32 XPGs in livers of male mice. For instance, CR decreased the male-predominantly expressed Oatp1a1 (97%) and increased the female-predominantly expressed Oatp1a4 (11). In conclusion, short-term CR alters the mRNA levels of over half of the 98 XPGs quantified in livers of male mice, and over half of these alterations appear to be due to feminization of the liver. - Highlights: • Utilized a graded CR model in male mice • The mRNA profiles of xenobiotic processing genes (XPGs) in liver were investigated. • CR up-regulates many phase-II enzymes. • CR tends to feminize the mRNA profiles of XPGs

Interference with Activator Protein-2 transcription factors leads to induction of apoptosis and an increase in chemo- and radiation-sensitivity in breast cancer cells

International Nuclear Information System (INIS)

Thewes, Verena; Orso, Francesca; Jäger, Richard; Eckert, Dawid; Schäfer, Sabine; Kirfel, Gregor; Garbe, Stephan; Taverna, Daniela; Schorle, Hubert

2010-01-01

Activator Protein-2 (AP-2) transcription factors are critically involved in a variety of fundamental cellular processes such as proliferation, differentiation and apoptosis and have also been implicated in carcinogenesis. Expression of the family members AP-2α and AP-2γ is particularly well documented in malignancies of the female breast. Despite increasing evaluation of single AP-2 isoforms in mammary tumors the functional role of concerted expression of multiple AP-2 isoforms in breast cancer remains to be elucidated. AP-2 proteins can form homo- or heterodimers, and there is growing evidence that the net effect whether a cell will proliferate, undergo apoptosis or differentiate is partly dependent on the balance between different AP-2 isoforms. We simultaneously interfered with all AP-2 isoforms expressed in ErbB-2-positive murine N202.1A breast cancer cells by conditionally over-expressing a dominant-negative AP-2 mutant. We show that interference with AP-2 protein function lead to reduced cell number, induced apoptosis and increased chemo- and radiation-sensitivity. Analysis of global gene expression changes upon interference with AP-2 proteins identified 139 modulated genes (90 up-regulated, 49 down-regulated) compared with control cells. Gene Ontology (GO) investigations for these genes revealed Cell Death and Cell Adhesion and Migration as the main functional categories including 25 and 12 genes, respectively. By using information obtained from Ingenuity Pathway Analysis Systems we were able to present proven or potential connections between AP-2 regulated genes involved in cell death and response to chemo- and radiation therapy, (i.e. Ctgf, Nrp1, Tnfaip3, Gsta3) and AP-2 and other main apoptosis players and to create a unique network. Expression of AP-2 transcription factors in breast cancer cells supports proliferation and contributes to chemo- and radiation-resistance of tumor cells by impairing the ability to induce apoptosis. Therefore, interference

Genome-wide discovery of drug-dependent human liver regulatory elements.

Directory of Open Access Journals (Sweden)

Robin P Smith

2014-10-01

Full Text Available Inter-individual variation in gene regulatory elements is hypothesized to play a causative role in adverse drug reactions and reduced drug activity. However, relatively little is known about the location and function of drug-dependent elements. To uncover drug-associated elements in a genome-wide manner, we performed RNA-seq and ChIP-seq using antibodies against the pregnane X receptor (PXR and three active regulatory marks (p300, H3K4me1, H3K27ac on primary human hepatocytes treated with rifampin or vehicle control. Rifampin and PXR were chosen since they are part of the CYP3A4 pathway, which is known to account for the metabolism of more than 50% of all prescribed drugs. We selected 227 proximal promoters for genes with rifampin-dependent expression or nearby PXR/p300 occupancy sites and assayed their ability to induce luciferase in rifampin-treated HepG2 cells, finding only 10 (4.4% that exhibited drug-dependent activity. As this result suggested a role for distal enhancer modules, we searched more broadly to identify 1,297 genomic regions bearing a conditional PXR occupancy as well as all three active regulatory marks. These regions are enriched near genes that function in the metabolism of xenobiotics, specifically members of the cytochrome P450 family. We performed enhancer assays in rifampin-treated HepG2 cells for 42 of these sequences as well as 7 sequences that overlap linkage-disequilibrium blocks defined by lead SNPs from pharmacogenomic GWAS studies, revealing 15/42 and 4/7 to be functional enhancers, respectively. A common African haplotype in one of these enhancers in the GSTA locus was found to exhibit potential rifampin hypersensitivity. Combined, our results further suggest that enhancers are the predominant targets of rifampin-induced PXR activation, provide a genome-wide catalog of PXR targets and serve as a model for the identification of drug-responsive regulatory elements.

Flavin-containing monooxygenase 3 (FMO3) role in busulphan metabolic pathway

Science.gov (United States)

Terelius, Ylva; Abedi-Valugerdi, Manuchehr; Naughton, Seán; Saghafian, Maryam; Moshfegh, Ali; Mattsson, Jonas; Potácová, Zuzana; Hassan, Moustapha

2017-01-01

Busulphan (Bu) is an alkylating agent used in the conditioning regimen prior to hematopoietic stem cell transplantation (HSCT). Bu is extensively metabolized in the liver via conjugations with glutathione to form the intermediate metabolite (sulfonium ion) which subsequently is degraded to tetrahydrothiophene (THT). THT was reported to be oxidized forming THT-1-oxide that is further oxidized to sulfolane and finally 3-hydroxysulfolane. However, the underlying mechanisms for the formation of these metabolites remain poorly understood. In the present study, we performed in vitro and in vivo investigations to elucidate the involvement of flavin-containing monooxygenase-3 (FMO3) and cytochrome P450 enzymes (CYPs) in Bu metabolic pathway. Rapid clearance of THT was observed when incubated with human liver microsomes. Furthermore, among different recombinant microsomal enzymes, the highest intrinsic clearance for THT was obtained via FMO3 followed by several CYPs including 2B6, 2C8, 2C9, 2C19, 2E1 and 3A4. In Bu- or THT-treated mice, inhibition of FMO3 by phenylthiourea significantly suppressed the clearance of both Bu and THT. Moreover, the simultaneous administration of a high dose of THT (200μmol/kg) to Bu-treated mice reduced the clearance of Bu. Consistently, in patients undergoing HSCT, repeated administration of Bu resulted in a significant up-regulation of FMO3 and glutathione-S-transfrase -1 (GSTA1) genes. Finally, in a Bu-treated patient, additional treatment with voriconazole (an antimycotic drug known as an FMO3-substrate) significantly altered the Bu clearance. In conclusion, we demonstrate for the first time that FMO3 along with CYPs contribute a major part in busulphan metabolic pathway and certainly can affect its kinetics. The present results have high clinical impact. Furthermore, these findings might be important for reducing the treatment-related toxicity of Bu, through avoiding interaction with other concomitant used drugs during conditioning and

Short-term calorie restriction feminizes the mRNA profiles of drug metabolizing enzymes and transporters in livers of mice

Energy Technology Data Exchange (ETDEWEB)

Fu, Zidong Donna [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Klaassen, Curtis D., E-mail: cklaasse@kumc.edu [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66160 (United States)

2014-01-01

Calorie restriction (CR) is one of the most effective anti-aging interventions in mammals. A modern theory suggests that aging results from a decline in detoxification capabilities and thus accumulation of damaged macromolecules. The present study aimed to determine how short-term CR alters mRNA profiles of genes that encode metabolism and detoxification machinery in the liver. Male C57BL/6 mice were fed CR (0, 15, 30, or 40%) diets for one month, followed by mRNA quantification of 98 xenobiotic processing genes (XPGs) in the liver, including 7 uptake transporters, 39 phase-I enzymes, 37 phase-II enzymes, 10 efflux transporters, and 5 transcription factors. In general, 15% CR did not alter mRNAs of most XPGs, whereas 30 and 40% CR altered over half of the XPGs (32 increased and 29 decreased). CR up-regulated some phase-I enzymes (fold increase), such as Cyp4a14 (12), Por (2.3), Nqo1 (1.4), Fmo2 (5.4), and Fmo3 (346), and numerous number of phase-II enzymes, such as Sult1a1 (1.2), Sult1d1 (2.0), Sult1e1 (33), Sult3a1 (2.2), Gsta4 (1.3), Gstm2 (1.3), Gstm3 (1.7), and Mgst3 (2.2). CR feminized the mRNA profiles of 32 XPGs in livers of male mice. For instance, CR decreased the male-predominantly expressed Oatp1a1 (97%) and increased the female-predominantly expressed Oatp1a4 (11). In conclusion, short-term CR alters the mRNA levels of over half of the 98 XPGs quantified in livers of male mice, and over half of these alterations appear to be due to feminization of the liver. - Highlights: • Utilized a graded CR model in male mice • The mRNA profiles of xenobiotic processing genes (XPGs) in liver were investigated. • CR up-regulates many phase-II enzymes. • CR tends to feminize the mRNA profiles of XPGs.

Young women selling sex online – narratives on regulating feelings

Directory of Open Access Journals (Sweden)

Jonsson LS

2015-02-01

Full Text Available Linda S Jonsson,1 Carl Göran Svedin,1 Margareta Hydén2 1Division of Child and Adolescent Psychiatry, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; 2Department of Social and Welfare Studies, Linköping University, Norrköping, Sweden Abstract: The current study concerns young women’s life stories of their experiences selling sex online before the age of 18. The aim was to gain an understanding of young women’s perceptions of the reasons they started, continued, and stopped selling sex. The study included interviews with 15 young women between the ages of 15 and 25 (M=18.9. Thematic analysis was used to identify similarities and differences in the narratives. Three themes and eight sub-themes were identified in relation to different stages in their lives in the sex trade. The themes were organized into three parts, each with its own storyline: “Entering – adverse life experiences”; traumatic events: feeling different and being excluded. “Immersion – using the body as a tool for regulating feelings”; being seen: being touched: being in control: affect regulation and self-harming. “Exiting – change or die”; living close to death: the process of quitting. The informants all had stable social lives in the sense that they had roofs over their heads, food to eat, and no substance-abuse issues. None had a third party who arranged the sexual contacts and none were currently trafficked. They described how their experiences of traumatic events and of feeling different and excluded had led them into the sex trade. Selling sex functioned as a way to be seen, to handle traumatic events, and to regulate feelings. Professionals working with young people who sell sex online need to understand the complex web of mixed feelings and emotional needs that can play a role in selling sex. Young people selling sex might need guidance in relationship building as well as help

Piper betle induces phase I & II genes through Nrf2/ARE signaling pathway in mouse embryonic fibroblasts derived from wild type and Nrf2 knockout cells.

Science.gov (United States)

Wan Hasan, Wan Nuraini; Kwak, Mi-Kyoung; Makpol, Suzana; Wan Ngah, Wan Zurinah; Mohd Yusof, Yasmin Anum

2014-02-23

Nuclear factor-erythroid 2 p45 related factor 2 (Nrf2) is a primary transcription factor, protecting cells from oxidative stress by regulating a number of antioxidants and phase II detoxifying enzymes. Dietary components such as sulforaphane in broccoli and quercetin in onions have been shown to be inducers of Nrf2. Piper betle (PB) grows well in tropical climate and the leaves are used in a number of traditional remedies for the treatment of stomach ailments and infections among Asians. The aim of this study was to elucidate the effect of Piper betle (PB) leaves extract in Nrf2 signaling pathway by using 2 types of cells; mouse embryonic fibroblasts (MEFs) derived from wild-type (WT) and Nrf2 knockout (N0) mice. WT and N0 cells were treated with 5 and 10 μg/ml of PB for 10 and 12-h for the determination of nuclear translocation of Nrf2 protein. Luciferase reporter gene activity was performed to evaluate the antioxidant response element (ARE)-induction by PB. Real-time PCR and Western blot were conducted on both WT and N0 cells after PB treatment for the determination of antioxidant enzymes [superoxide dismutase (SOD1) and heme-oxygenase (HO-1)], phase I oxidoreductase enzymes [ quinone oxidoreductase (NQO1)] and phase II detoxifying enzyme [glutathione S-transferase (GST)]. Nuclear translocation of Nrf2 by PB in WT cells was better after 10 h incubation compared to 12 h. Real time PCR and Western blot analysis showed increased expressions of Nrf2, NQO1 and GSTA1 genes with corresponding increases in glutathione, NQO1 and HO-1 proteins in WT cells. Reporter gene ARE was stimulated by PB as shown by ARE/luciferase assay. Interestingly, PB induced SOD1 gene and protein expressions in N0 cells but not in WT cells. The results of this study confirmed that PB activated Nrf2-ARE signaling pathway which subsequently induced some phase I oxidoreductase, phase II detoxifying and antioxidant genes expression via ARE reporter gene involved in the Nrf2 pathway with the

Fimasartan, a Novel Angiotensin-Receptor Blocker, Protects against Renal Inflammation and Fibrosis in Mice with Unilateral Ureteral Obstruction: the Possible Role of Nrf2

Science.gov (United States)

Kim, Soojeong; Kim, Sung Jun; Yoon, Hye Eun; Chung, Sungjin; Choi, Bum Soon; Park, Cheol Whee; Shin, Seok Joon

2015-01-01

Objectives: A newly developed angiotensin II receptor blocker, fimasartan, is effective in lowering blood pressure through its action on the renin-angiotensin system. Renal interstitial fibrosis, believed to be due to oxidative injury, is an end-stage process in the progression of chronic kidney disease. Nuclear factor erythroid 2-related factor 2 (Nrf2) is known to regulate cellular oxidative stress and induce expression of antioxidant genes. In this study we investigated the role of Nrf2 in fimasartan-mediated antioxidant effects in mice with renal fibrosis induced by unilateral ureteral obstruction (UUO). Materials and Methods: UUO was induced surgically in mice, followed by either no treatment with fimasartan or the intraperitoneal administration of fimasartan (3 mg/kg/day). On day 7, we evaluated the changes in the renin-angiotensin system (RAS) and the expression of Nrf2 and its downstream antioxidant genes, as well as renal inflammation, apoptosis, and fibrosis in the obstructed kidneys. The effect of fimasartan on the Nrf2 pathway was also investigated in HK-2 cells stimulated by tumor necrosis factor-α. Results: The mice with surgically induced UUO showed increased renal inflammation and fibrosis as evidenced by histopathologic findings and total collagen content in the kidney. These effects were attenuated in the obstructed kidneys of the fimasartan-treated mice. Fimasartan treatment inhibited RAS activation and the expression of Nox1, Nox2, and Nox4. In contrast, fimasartan upregulated the renal expression of Nrf2 and its downstream signaling molecules (such as NQO1; HO-1; GSTa2 and GSTm3). Furthermore, it increased the expression of antioxidant enzymes, including CuSOD, MnSOD, and catalase. The fimasartan-treated mice had significantly less apoptosis on TUNEL staining, with decreased levels of pro-apoptotic protein and increased levels of anti-apoptotic protein. In the HK-2 cells, fimasartan treatment inhibited RAS activation, decreased expression of

Patterns of dioxin-altered mRNA expression in livers of dioxin-sensitive versus dioxin-resistant rats

Energy Technology Data Exchange (ETDEWEB)

Franc, Monique A. [University of Toronto, Department of Pharmacology and Toxicology, Medical Sciences Building, Toronto, ON (Canada); Johnson and Johnson Pharmaceutical Research and Development, Department of Pharmacogenomics, 1000 Route 202 South, P.O. Box 300, Raritan, NJ (United States); Moffat, Ivy D.; Boutros, Paul C.; Okey, Allan B. [University of Toronto, Department of Pharmacology and Toxicology, Medical Sciences Building, Toronto, ON (Canada); Tuomisto, Jouni T.; Tuomisto, Jouko [National Public Health Institute, Department of Environmental Health, Centre for Environmental Health Risk Analysis, Kuopio (Finland); Pohjanvirta, Raimo [University of Helsinki, Department of Food and Environmental Hygiene, Faculty of Veterinary Medicine, Helsinki (Finland)

2008-11-15

Dioxins exert their major toxicologic effects by binding to the aryl hydrocarbon receptor (AHR) and altering gene transcription. Numerous dioxin-responsive genes previously were identified both by conventional biochemical and molecular techniques and by recent mRNA expression microarray studies. However, of the large set of dioxin-responsive genes the specific genes whose dysregulation leads to death remain unknown. To identify specific genes that may be involved in dioxin lethality we compared changes in liver mRNA levels following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in three strains/lines of dioxin-sensitive rats with changes in three dioxin-resistant rat strains/lines. The three dioxin-resistant strains/lines all harbor a large deletion in the transactivation domain of the aryl hydrocarbon receptor (AHR). Despite this deletion, many genes exhibited a ''Type-I'' response - that is, their responses were similar in dioxin-sensitive and dioxin-resistant rats. Several genes that previously were well established as being dioxin-responsive or under AHR regulation emerged as Type-I responses (e.g. CYP1A1, CYP1A2, CYP1B1 and Gsta3). In contrast, a relatively small number of genes exhibited a Type-II response - defined as a difference in responsiveness between dioxin-sensitive and dioxin-resistant rat strains. Type-II genes include: malic enzyme 1, ubiquitin C, cathepsin L, S-adenosylhomocysteine hydrolase and ferritin light chain 1. In silico searches revealed that AH response elements are conserved in the 5'-flanking regions of several genes that respond to TCDD in both the Type-I and Type-II categories. The vast majority of changes in mRNA levels in response to 100 {mu}g/kg TCDD were strain-specific; over 75% of the dioxin-responsive clones were affected in only one of the six strains/lines. Selected genes were assessed by quantitative RT-PCR in dose-response and time-course experiments and responses of some genes were

Nrf2-inducing anti-oxidation stress response in the rat liver--new beneficial effect of lansoprazole.

Science.gov (United States)

Yamashita, Yasunobu; Ueyama, Takashi; Nishi, Toshio; Yamamoto, Yuta; Kawakoshi, Akatsuki; Sunami, Shogo; Iguchi, Mikitaka; Tamai, Hideyuki; Ueda, Kazuki; Ito, Takao; Tsuruo, Yoshihiro; Ichinose, Masao

2014-01-01

Lansoprazole is a potent anti-gastric ulcer drug that inhibits gastric proton pump activity. We identified a novel function for lansoprazole, as an inducer of anti-oxidative stress responses in the liver. Gastric administration of lansoprazole (10-100 mg/kg) to male Wistar rats produced a dose-dependent increase in hepatic mRNA levels of nuclear factor, erythroid-derived 2, -like 2 (Nrf2), a redox-sensitive transcription factor, at 3 h and Nrf2 immunoreactivity (IR) in whole hepatic lysates at 6 h. Conversely, the levels of Kelch-like ECH-associated protein (Keap1), which sequesters Nrf2 in the cytoplasm under un-stimulated conditions, were unchanged. Translocation of Nrf2 into the nuclei of hepatocytes was observed using western blotting and immunohistochemistry. Expression of mRNAs for Nrf2-dependent antioxidant and phase II enzymes, such as heme oxygenase 1 (HO-1), NAD (P) H dehydrogenase, quinone 1 (Nqo1), glutathione S-transferase A2 (Gsta2), UDP glucuronosyltransferase 1 family polypeptide A6 (Ugt1a6), were dose-dependently up-regulated at 3 h. Furthermore, the levels of HO-1 IR were dose-dependently increased in hepatocytes at 6 h. Subcutaneous administration of lansoprazole (30 mg/kg/day) for 7 successive days resulted in up-regulation and nuclear translocation of Nrf2 IR in hepatocytes and up-regulation of HO-1 IR in the liver. Pretreatment with lansoprazole attenuated thioacetamide (500 mg/kg)-induced acute hepatic damage via both HO-1-dependent and -independent pathways. Up-stream networks related to Nrf2 expression were investigated using microarray analysis, followed by data mining with Ingenuity Pathway Analysis. Up-regulation of the aryl hydrocarbon receptor (AhR)-cytochrome P450, family 1, subfamily a, polypeptide 1 (Cyp1a1) pathway was associated with up-regulation of Nrf2 mRNA. In conclusion, lansoprazole might have an alternative indication in the prevention and treatment of oxidative hepatic damage through the induction of both phase I and phase

Nrf2-Inducing Anti-Oxidation Stress Response in the Rat Liver - New Beneficial Effect of Lansoprazole

Science.gov (United States)

Yamashita, Yasunobu; Ueyama, Takashi; Nishi, Toshio; Yamamoto, Yuta; Kawakoshi, Akatsuki; Sunami, Shogo; Iguchi, Mikitaka; Tamai, Hideyuki; Ueda, Kazuki; Ito, Takao; Tsuruo, Yoshihiro; Ichinose, Masao

2014-01-01

Lansoprazole is a potent anti-gastric ulcer drug that inhibits gastric proton pump activity. We identified a novel function for lansoprazole, as an inducer of anti-oxidative stress responses in the liver. Gastric administration of lansoprazole (10–100 mg/kg) to male Wistar rats produced a dose-dependent increase in hepatic mRNA levels of nuclear factor, erythroid-derived 2, -like 2 (Nrf2), a redox-sensitive transcription factor, at 3 h and Nrf2 immunoreactivity (IR) in whole hepatic lysates at 6 h. Conversely, the levels of Kelch-like ECH-associated protein (Keap1), which sequesters Nrf2 in the cytoplasm under un-stimulated conditions, were unchanged. Translocation of Nrf2 into the nuclei of hepatocytes was observed using western blotting and immunohistochemistry. Expression of mRNAs for Nrf2-dependent antioxidant and phase II enzymes, such as heme oxygenase 1 (HO-1), NAD (P) H dehydrogenase, quinone 1 (Nqo1), glutathione S-transferase A2 (Gsta2), UDP glucuronosyltransferase 1 family polypeptide A6 (Ugt1a6), were dose-dependently up-regulated at 3 h. Furthermore, the levels of HO-1 IR were dose-dependently increased in hepatocytes at 6 h. Subcutaneous administration of lansoprazole (30 mg/kg/day) for 7 successive days resulted in up-regulation and nuclear translocation of Nrf2 IR in hepatocytes and up-regulation of HO-1 IR in the liver. Pretreatment with lansoprazole attenuated thioacetamide (500 mg/kg)-induced acute hepatic damage via both HO-1-dependent and -independent pathways. Up-stream networks related to Nrf2 expression were investigated using microarray analysis, followed by data mining with Ingenuity Pathway Analysis. Up-regulation of the aryl hydrocarbon receptor (AhR)-cytochrome P450, family 1, subfamily a, polypeptide 1 (Cyp1a1) pathway was associated with up-regulation of Nrf2 mRNA. In conclusion, lansoprazole might have an alternative indication in the prevention and treatment of oxidative hepatic damage through the induction of both phase I and

Comparative liver accumulation of dioxin-like compounds in sheep and cattle: Possible role of AhR-mediated xenobiotic metabolizing enzymes.

Science.gov (United States)

Girolami, F; Spalenza, V; Benedetto, A; Manzini, L; Badino, P; Abete, M C; Nebbia, C

2016-11-15

PCDDs, PCDFs, and PCBs are persistent organic pollutants (POPs) that accumulate in animal products and may pose serious health problems. Those able to bind the aryl hydrocarbon receptor (AhR), eliciting a plethora of toxic responses, are defined dioxin-like (DL) compounds, while the remainders are called non-DL (NDL). An EFSA opinion has highlighted the tendency of ovine liver to specifically accumulate DL-compounds to a greater extent than any other farmed ruminant species. To examine the possible role in such an accumulation of xenobiotic metabolizing enzymes (XME) involved in DL-compound biotransformation, liver samples were collected from ewes and cows reared in an area known for low dioxin contamination. A related paper reported that sheep livers had about 5-fold higher DL-compound concentrations than cattle livers, while the content of the six marker NDL-PCBs did not differ between species. Specimens from the same animals were subjected to gene expression analysis for AhR, AhR nuclear translocator (ARNT) and AhR-dependent oxidative and conjugative pathways; XME protein expression and activities were also investigated. Both AhR and ARNT mRNA levels were about 2-fold lower in ovine samples and the same occurred for CYP1A1 and CYP1A2, being approximately 3- and 9-fold less expressed in sheep compared to cattle, while CYP1B1 could be detectable in cattle only. The results of the immunoblotting and catalytic activity (most notably EROD) measurements of the CYP1A family enzymes were in line with the gene expression data. By contrast, phase II enzyme expression and activities in sheep were higher (UGT1A) or similar (GSTA1, NQO1) to those recorded in cattle. The overall low expression of CYP1 family enzymes in the sheep is in line with the observed liver accumulation of DL-compounds and is expected to affect the kinetics and the dynamics of other POPs such as many polycyclic aromatic hydrocarbons, as well as of toxins (e.g. aflatoxins) or drugs (e.g. benzimidazole

Protective role for ovarian glutathione S-transferase isoform pi during 7,12-dimethylbenz[a]anthracene-induced ovotoxicity

Energy Technology Data Exchange (ETDEWEB)

Bhattacharya, Poulomi, E-mail: poulomib@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

2012-04-15

7,12-Dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles at all developmental stages. This study investigated a role for the glutathione S-transferase (Gst) isoforms alpha (a), mu (m) and pi (p) and the transcription factors, Ahr and Nrf2, during DMBA-induced ovotoxicity, and their regulation by phosphatidylinositol-3 kinase (PI3K) signaling. Negative regulation of JNK by GSTP during DMBA exposure was also studied. Post-natal day (PND) 4 Fischer 344 rat ovaries were exposed to vehicle control (1% DMSO) ± DMBA (1 μM) or vehicle control (1% DMSO) ± LY294002 (PI3K inhibitor; 20 μM) for 1, 2, 4, or 6 days. Total RNA or protein was isolated, followed by RT-PCR or Western blotting to determine mRNA or protein level, respectively. Immunoprecipitation using an anti-GSTP antibody was performed to determine interaction between GSTP and JNK, followed by Western blotting to determine JNK and p-c-Jun protein level. DMBA had no impact on Gsta, Gstm or Nrf2 mRNA level, but increased Gstp mRNA and protein after 2 days. Ahr mRNA and protein increased after 2 and 4 days of DMBA exposure, respectively and DMBA increased NRF2 protein level after 4 days. JNK bound to GSTP was increased during DMBA exposure, with a concomitant decrease in unbound JNK and p-c-Jun. Ahr and Gstp mRNA were decreased (2 days) and increased (4 days) by PI3K inhibition, while Gstm mRNA increased (P < 0.05) after both time points, and there was no effect on Nrf2 mRNA. PI3K inhibition increased AHR, NRF2 and GSTP protein level. These findings support involvement of ovarian GSTP during DMBA exposure, and indicate a regulatory role for the PI3K signaling pathway on ovarian xenobiotic metabolism gene expression. -- Highlights: ► Ovarian GSTP is activated in response to DMBA exposure. ► AhR and Nrf2 transcription factors are up-regulated by DMBA. ► PI3K signaling regulates Ahr, Nrf2 and Gstp expression. ► GSTP negatively regulates ovarian JNK in response to DMBA exposure.

Esamojo laiko formantas -st- išvestiniuose lietuvių kalbos veiksmažodžiuose

Directory of Open Access Journals (Sweden)

Jurgis Pakerys

2011-12-01

the electronic edition of “Lietuvių kalbos žodynas” (http://www.lkz.lt and arranged according to suffixes.The class of verbs in ‑auti has 8 formations which are based on the stems in ‑sta: blė́stauti ‘to burn lightly, to be burning down’ : blė́sta ‘burns down’, nubostauti ‘to ask for something in a bothersome way’ : nubósta ‘gets bored, becomes boring’, nerimstauti ‘to be bored, to wander’ : nerìmsta ‘is not calm’, nirštauti ‘to be (slightly angry’ : nir̃šta ‘is angry, rages’, pýkstauti ‘to be angry’ : pỹksta ‘is angry’, širstauti ‘to rage’ : šir̃sta ‘rages’, trókštauti ‘to desire’ : trókšta ‘desires’, vargstáuti ‘to live in trouble, to have difficulties’ : var̃gsta ‘lives in poverty, takes trouble’.The class in ‑enti provides 3 examples: birsténti ‘to scatter, to strew (slightly’ : (dialectal bìrsta ‘pours out (intr.’ (therefore, the formation is causative, blėsténti ‘to burn slightly, to go out’ : blė́sta ‘burns down’, rūksténti ‘to emit smoke little by little’ : rū̃ksta ‘emits smoke’.The formations in ‑ėti based on the stems in ‑sta are the following: drįstė́ti, ‑ė́ja ‘to dare’ : drį̃sta ‘dares’, numirštė́ti, ‑ė́ja ‘to die (about animals’ : numìršta ‘dies’, plū́stėti, plū́sta ‘to talk nonsense’ : plū́sta ‘talks nonsense’, rūkstė́ti, ‑ė́ja ‘to emit smoke’ : rū̃ksta ‘emits smoke’, smilkstė́ti, smil̃ksta ‘to burn without fire, to smoulder’ : smil̃ksta ‘smoulders’, spurstė́ti, spùrsta ‘to flounder’ : spùrsta ‘flounders’, várgstėti, ‑ėja ‘to live in trouble, to have difficulties’ : var̃gst‑a ‘lives in poverty, takes trouble’. It is possible that in some cases the verbs were not really derived, but rather reshaped according to the model of tekė́ti, tẽka (the inflectional stems in ‑st‑(a became lexical, e. g. t�

Testing an aflatoxin B1 gene signature in rat archival tissues.

Science.gov (United States)

Merrick, B Alex; Auerbach, Scott S; Stockton, Patricia S; Foley, Julie F; Malarkey, David E; Sills, Robert C; Irwin, Richard D; Tice, Raymond R

2012-05-21

Archival tissues from laboratory studies represent a unique opportunity to explore the relationship between genomic changes and agent-induced disease. In this study, we evaluated the applicability of qPCR for detecting genomic changes in formalin-fixed, paraffin-embedded (FFPE) tissues by determining if a subset of 14 genes from a 90-gene signature derived from microarray data and associated with eventual tumor development could be detected in archival liver, kidney, and lung of rats exposed to aflatoxin B1 (AFB1) for 90 days in feed at 1 ppm. These tissues originated from the same rats used in the microarray study. The 14 genes evaluated were Adam8, Cdh13, Ddit4l, Mybl2, Akr7a3, Akr7a2, Fhit, Wwox, Abcb1b, Abcc3, Cxcl1, Gsta5, Grin2c, and the C8orf46 homologue. The qPCR FFPE liver results were compared to the original liver microarray data and to qPCR results using RNA from fresh frozen liver. Archival liver paraffin blocks yielded 30 to 50 μg of degraded RNA that ranged in size from 0.1 to 4 kB. qPCR results from FFPE and fresh frozen liver samples were positively correlated (p ≤ 0.05) by regression analysis and showed good agreement in direction and proportion of change with microarray data for 11 of 14 genes. All 14 transcripts could be amplified from FFPE kidney RNA except the glutamate receptor gene Grin2c; however, only Abcb1b was significantly upregulated from control. Abundant constitutive transcripts, S18 and β-actin, could be amplified from lung FFPE samples, but the narrow RNA size range (25-500 bp length) prevented consistent detection of target transcripts. Overall, a discrete gene signature derived from prior transcript profiling and representing cell cycle progression, DNA damage response, and xenosensor and detoxication pathways was successfully applied to archival liver and kidney by qPCR and indicated that gene expression changes in response to subchronic AFB1 exposure occurred predominantly in the liver, the primary target for AFB1-induced

IncobotulinumtoxinA in aesthetics: Russian multidisciplinary expert consensus recommendations

Directory of Open Access Journals (Sweden)

Yutskovskaya Y

2015-06-01

Full Text Available Yana Yutskovskaya,1 Elena Gubanova,2 Irina Khrustaleva,3 Vasiliy Atamanov,4 Anastasiya Saybel,5 Elena Parsagashvili,6 Irina Dmitrieva,7 Elena Sanchez,8 Natalia Lapatina,9 Tatiana Korolkova,10 Alena Saromytskaya,11 Elena Goltsova,12 Elmira Satardinova13 1Department of Dermatovenereology and Cosmetology, Pacific State Medical University, Vladivostock, 2Department of Skin and Venereal Diseases, Postgraduate Medical Institute, Moscow National University of Food Production, Moscow, 3Department of Plastic Surgery, IP Pavlov Medical State University, St Petersburg, 4Department of Reconstructive and Plastic Surgery, SN Fedorova, Federal State Institution, Novosibirsk, 5Clinic Ideal, Laser Technologies Center, Moscow, 6Aestima-clinic, 7Clinic “Academy”, St Petersburg, 8Eklan Medical Center of Cosmetological Correction, 9Clinic of Aesthetic Medicine and Plastic Surgery, Moscow, 10Department of Cosmetology, II Mechnikov North-Western State Medical University, St Petersburg, 11Plastic Surgery Clinic, Center of Aesthetic Medicine and Beauty Cosmetology, 12“Neo-Clinic,” Tyumen, 13Botulinum Toxin Therapy Department, Diagnostic Center of the Irkutsk State Medical Academy of Postgraduate Education, Irkutsk, Russia Background: Although there are various international consensus recommendations on the use of botulinum neurotoxin type A (BoNT/A in facial aesthetics, there are no global or Russian guidelines on the optimal dose of incobotulinumtoxinA, free from complexing proteins, within specific aesthetic indications. This article reports the outcomes of two expert consensus meetings, conducted to review and analyze efficacy and tolerability data for incobotulinumtoxinA in various facial aesthetic indications and to give expert consensus recommendations to ensure best clinical practice among Russian clinicians. Methods: Thirteen dermatology and/or plastic surgery experts attended meetings held in Paris, France (November 2013, and Moscow, Russia (March 2014

Colloid transport in model fracture filling materials

Science.gov (United States)

Wold, S.; Garcia-Garcia, S.; Jonsson, M.

2010-12-01

Colloid transport in model fracture filling materials Susanna Wold*, Sandra García-García and Mats Jonsson KTH Chemical Science and Engineering Royal Institute of Technology, SE-100 44 Stockholm, Sweden *Corresponding author: E-mail: wold@kth.se Phone: +46 8 790 6295 In colloid transport in water-bearing fractures, the retardation depends on interactions with the fracture surface by sorption or filtration. These mechanisms are difficult to separate. A rougher surface will give a larger area available for sorption, and also when a particle is physically hindered, it approaches the surface and enables further sorption. Sorption can be explained by electrostatics were the strongest sorption on minerals always is observed at pH below pHpzc (Filby et al., 2008). The adhesion of colloids to mineral surfaces is related to the surface roughness according to a recent study (Darbha et al., 2010). There is a large variation in the characteristics of water-bearing fractures in bedrock in terms of aperture distribution, flow velocity, surface roughness, mineral distributions, presence of fracture filling material, and biological and organic material, which is hard to implement in modeling. The aim of this work was to study the transport of negatively charged colloids in model fracture filling material in relation to flow, porosity, mineral type, colloid size, and surface charge distribution. In addition, the impact on transport of colloids of mixing model fracture filling materials with different retention and immobilization capacities, determined by batch sorption experiments, was investigated. The transport of Na-montmorillonite colloids and well-defined negatively charged latex microspheres of 50, 100, and 200 nm diameter were studied in either columns containing quartz or quartz mixed with biotite. The ionic strength in the solution was exclusively 0.001 and pH 6 or 8.5. The flow rates used were 0.002, 0.03, and 0.6 mL min-1. Sorption of the colloids on the model fracture

DISTRIBUIÇÃO E TRANSPORTE DE SEDIMENTOS COSTEIROS. EXEMPLOS EM ARRAIAL DO CABO, RJ

Directory of Open Access Journals (Sweden)

Paula Motta

2018-04-01

Full Text Available O trabalho discute temas relacionados à distribuição de sedimentos costeiros, parâmetros granulométricos e modelos bidimensionais de transporte de sedimentos. Parte-se da hipótese de que a disposição dos materiais na superfície de fundo das enseadas permite o diagnóstico de processos associados à hidrodinâmica marinha e sua participação no controle do transporte e distribuição dos sedimentos costeiros. O objetivo central é então caracterizar a textura superficial do depósito costeiro e apresentar correlações entre os parâmetros estatísticos que permitam o diagnóstico de processos relacionados à distribuição e ao transporte dos sedimentos no sistema praia-antepraia. Como área de pesquisa, foram selecionadas três enseadas no município de Arraial do Cabo (RJ. As etapas metodológicas partiram da definição de uma malha amostral, coleta de 96 amostras de sedimentos em profundidades entre 1 e 23 metros, seguido por análises granulométricas em laboratório, determinação de parâmetros estatísticos e cálculo do modelo de tendências de transporte de sedimentos (GSTA. Os resultados apontam a ocorrência majoritária de areias finas (41,6% e médias (17,7% moderadamente bem selecionadas como o principal depósito nas enseadas, no entanto, além dos depósitos palimpsestos, núcleos de deposição de areias grossas (14,6% e muito grossas (8,3% e, por outro lado, areias muito finas (5,2% e siltes (6,2% também foram identificados e discutidos à luz de sua significância ambiental. Quanto ao modelo de transporte, o melhor ajuste (65% foi feito com o padrão FB, que indica sedimentos mais finos e mais bem selecionados na direção do transporte. Conclui-se que os depósitos palimpsestos são responsáveis pelo abastecimento da praia emersa e que os esforços de interpretação dos parâmetros estatísticos e a geração de resultados de transporte de sedimentos a partir de modelos não hidrodinâmicos geram informa

Low-pH concrete plug for sealing the KBS-3V deposition tunnels

International Nuclear Information System (INIS)

Malm, Richard

2012-01-01

on being watertight, which also affects the design of the concrete plug. In the spent fuel repository, low-pH concrete should be used instead of conventional concrete. The reason for this is to the largest extent to reduce the negative effect that basic materials could have on the function of the bentonite clay. For this purpose, a new low-pH concrete recipe has been developed and this changes the conditions for using reinforcement, cooling and grouting compared to the use of conventional concrete. The report shows the possibilities to use an unreinforced plug made of low-pH concrete as a resistance in the deposition tunnels. Today, some parameters are unknown and some data may be classified as uncertain, primarily regarding the long-term properties of the low-pH concrete material and the bentonite clay. It will take several years until all questions can be answered and a full-scale test is vital to validate the assumptions and the performed numerical simulations. The report should therefore be considered based on that data and conclusions will be studied further and be experimentally verified under realistic and controlled conditions. The project group consists of: Patrik Gatter (VPC), Richard Malm (VPC), Lennart Boergesson (Clay Technology AB), Lars-Olof Dahlstroem (NCC-Teknik), Jonas Magnusson (NCC-Teknik), Christina Claeson-Jonsson (NCC-Teknik), Morgan Johansson (Reinertsen), Rikard Karlzen (SKB), Paer Grahm (SKB), Sten Palmer (Sten Palmer Engineering AB) and Hans Wimelius (NCC AB)

Low-pH concrete plug for sealing the KBS-3V deposition tunnels

Energy Technology Data Exchange (ETDEWEB)

Malm, Richard (Vattenfall Power Consultant AB (Sweden))

2012-01-15

requirement on being watertight, which also affects the design of the concrete plug. In the spent fuel repository, low-pH concrete should be used instead of conventional concrete. The reason for this is to the largest extent to reduce the negative effect that basic materials could have on the function of the bentonite clay. For this purpose, a new low-pH concrete recipe has been developed and this changes the conditions for using reinforcement, cooling and grouting compared to the use of conventional concrete. The report shows the possibilities to use an unreinforced plug made of low-pH concrete as a resistance in the deposition tunnels. Today, some parameters are unknown and some data may be classified as uncertain, primarily regarding the long-term properties of the low-pH concrete material and the bentonite clay. It will take several years until all questions can be answered and a full-scale test is vital to validate the assumptions and the performed numerical simulations. The report should therefore be considered based on that data and conclusions will be studied further and be experimentally verified under realistic and controlled conditions. The project group consists of: Patrik Gatter (VPC), Richard Malm (VPC), Lennart Boergesson (Clay Technology AB), Lars-Olof Dahlstroem (NCC-Teknik), Jonas Magnusson (NCC-Teknik), Christina Claeson-Jonsson (NCC-Teknik), Morgan Johansson (Reinertsen), Rikard Karlzen (SKB), Paer Grahm (SKB), Sten Palmer (Sten Palmer Engineering AB) and Hans Wimelius (NCC AB)

Gas stunning with CO2 affected meat color, lipid peroxidation, oxidative stress, and gene expression of mitogen-activated protein kinases, glutathione S-transferases, and Cu/Zn-superoxide dismutase in the skeletal muscles of broilers.

Science.gov (United States)

Xu, Lei; Zhang, Haijun; Yue, Hongyuan; Wu, Shugeng; Yang, Haiming; Wang, Zhiyue; Qi, Guanghai

2018-01-01

Meat color and lipid peroxidation are important traits related to meat quality. CO 2 concentration is a critical factor that can affect meat quality in the commercial use of gas stunning (GS). However, the effect and mechanism of CO 2 stunning on meat color and lipid peroxidation during long-term storage remain poorly studied. We aimed to study the effects of GS methods, especially CO 2 concentration, on meat color and meat lipid peroxidation in broilers during long-term storage at 4 °C and to explore the potential mechanism of meat color change via lipid peroxidation and the inner lipid peroxide scavenging system. Eighteen broilers were sacrificed after exposure to one of the following gas mixtures for 90 s: 40% CO 2  + 21% O 2  + 39% N 2 (G40%), 79% CO 2  + 21% O 2 (G79%), or no stunning (0% CO 2 , control). Meat color, serum variables, enzyme activities, and the gene expression of mitogen-activated protein kinase ( MAPK ), nuclear factor-erythroid 2-related factor 2 ( Nrf2 ), glutathione S-transferase ( GST ) and superoxide dismutase ( SOD ) were determined. The concentrations of serum triiodothyronine (T3, P  = 0.03) and the ratio of serum free triiodothyronine/free thyroxine (FT3/FT4, P  meat and the TBARS 3 d in thigh meat ( P  meat ( r  = - 0.63, P  meat and in the thigh meat ( r  = - 0.57, P  = 0.01; and r  = - 0.53, P  = 0.03 respectively). Compared with the control group, Lightness (L*) 1 d ( P =  0.03) and L* 9 d ( P meat of both the G40% and G79% groups. The values of yellowness (b*) 3 d ( P =  0.01), b* 6 d ( P meat were lower in both the G40% and G79% groups than in the control group. In the breast muscle, the mRNA levels of c-Jun N-terminal kinase 2 ( JNK2, P  = 0.03), GSTT1 ( P  = 0.04), and SOD1 ( P  = 0.05) were decreased, and the mRNA levels of JNK1 ( P  = 0.07), Nrf2 ( P  = 0.09), and GSTA3 ( P  = 0.06) were slightly lower in both the G40% and G79% groups

Book Reviews

Directory of Open Access Journals (Sweden)

Redactie KITLV

2008-12-01

Melaka and Enyan anak Usen, Iban art; Sexual selection and severed heads: weaving, sculpture, tattooing and other arts of the Iban of Borneo (Viktor T. King John Roosa; Pretext for mass murder; The September 30th Movement and Suharto’s coup d’état in Indonesia (Gerry van Klinken Vladimir Braginsky; The heritage of traditional Malay literature; A historical survey of genres, writings and literary views (Dick van der Meij Joel Robbins, Holly Wardlow (eds; The making of global and local modernities in Melanesia; Humiliation, transformation and the nature of cultural change (Toon van Meijl Kwee Hui Kian; The political economy of Java’s northeast coast c. 1740-1800; Elite synergy (Luc Nagtegaal Charles A. Coppel (ed.; Violent conflicts in Indonesia; Analysis, representation, resolution (Gerben Nooteboom Tom Therik; Wehali: the female land; Traditions of a Timorese ritual centre (Dianne van Oosterhout Patricio N. Abinales, Donna J. Amoroso; State and society in the Philippines (Portia L. Reyes Han ten Brummelhuis; King of the waters; Homan van der Heide and the origin of modern irrigation in Siam (Jeroen Rikkerink Hotze Lont; Juggling money; Financial self-help organizations and social security in Yogyakarta (Dirk Steinwand Henk Maier; We are playing relatives; A survey of Malay writing (Maya Sutedja-Liem Hjorleifur Jonsson; Mien relations; Mountain people and state control in Thailand (Nicholas Tapp Lee Hock Guan (ed.; Civil society in Southeast Asia (Bryan S. Turner Jan Mrázek; Phenomenology of a puppet theatre; Contemplations on the art of Javanese wayang kulit (Sarah Weiss Janet Steele; Wars within; The story of Tempo, an independent magazine in Soeharto’s Indonesia (Robert Wessing REVIEW ESSAY Sean Turnell; Burma today Kyaw Yin Hlaing, Robert Taylor, Tin Maung Maung Than (eds; Myanmar; Beyond politics to societal imperatives Monique Skidmore (ed.; Burma at the turn of the 21st century Mya Than; Myanmar in ASEAN

EDITORIAL: World Year of Physics 2005 Focus on Photoemission and Electronic Structure

Science.gov (United States)

2005-04-01

, ultra-precise clocks and, at some point, maybe true nanomachines. Focus on Nano-electromechanical Systems Contents Thermomechanical noise limits on parametric sensing with nanomechanical resonators A Cleland Dynamics of a nanomechanical resonator coupled to a superconducting single-electron transistor M Blencowe, J Imbers and A Armour Simple models suffice for the single dot quantum shuttle A Donarini, T Novotny and A-P Jauho Quantum nano-electromechanics with electrons, quasiparticles and Cooper pairs: effective bath descriptions and strong feedback effects A Clerk and S Bennett Nuclear wave function interference in single-molecule electron transport M R Wegewijs and K C Nowack Self-excitation in nanoelectromechanical charge shuttles below the field emission regime F Rüting, A Erbe and C Weiss Formation of micro-tubes from strained SiGe/Si heterostructures H Qin, N Shaji, N E Merrill, H S Kim, R C Toonen, R H Blick, M M Roberts, D Savage, M G Lagally and G Celler Spin-controlled nanoelectromechanics in magnetic NEM-SET systems L Y Gorelik, D Fedorets, R I Shekhter and M Jonson Coupling between electronic transport and longitudinal phonons in suspended nanotubes S Sapmaz, P Jarillo-Herrero, Ya M Blanter and H van der Zant Phonon-assisted tunneling in interacting suspended single wall carbon nanotubes W Izumida and M Grifoni Theoretical and experimental investigations of three-terminal carbon nanotube relays S Axelsson, E E B Campbell, L M Jonsson, J M Kinaret, S W Lee, Y W Park and M Sveningsson Quantum dots in Si/SiGe 2DEGs with Schottky top-gated leads K A Slinker, K L M Lewis, C C Haselby, S Goswami, L J Klein, J O Chu, S N Coppersmith and R Joynt VHF, UHF and microwave frequency nanomechanical resonators X M H Huang, X L Feng, C A Zorman, M Mehregany and M Roukes Robert H Blick, University of Wisconsin at Madison, USA Milena Grifoni, Universität Regensburg, Germany

Effects of forest fertilization on nitrate and crude protein content in some important reindeer forage species

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Gustaf Åhman

1984-05-01

after three years. Fertilization caused a drastic development of hair-grass. This resulted in the formation of a carpet of dead leaves and straw in the autumn (picture 3 - 5.Skogsgödslingens inverkan på nitrat- och råproteininnehållet i några viktiga renbetesväxter.Abstract in Swedish / Sammanfattning: Vid gödsling av skogsmark som betas av ren år det möjligt att renen kan få i sig ammoniumnitrat, dels genom att äta av gödselkorn som ligger på marken eller via dricksvatten. Den kan också f å i sig nitrat som upptagits och lagrats i betesväxter. Den sistnämnda faktorn belyses i denna rapport. Dessutom redovisas resultat av undersökningar gallande gödslingens inverkan på betesväxternas råproteinhalt. Undersokningen genomfordes på två forsoksområden, den ena av torr ristyp och den andra av frisk ristyp. Områdena var belägna 10 respektive 15 km nordväst om Lycksele. Tre olika gödselgivor (75, 150 och 250 kg N/ha av ammoniumnitrat och en giva (150 kg N/ha av urea testades. Spridningen av godsei skedde vid två tillfällen, i juni och i juli. Fôr undersokning av gödslingens påverkan på nitrat- och råproteinhalterna i några vanliga renbetesväxter togs prov av renlav, ljung, kråkris, lingonris, blåbårsris och kruståtel vid olika tidpunkter efter gödsling. Någon nämnvärd kontaminering av nitrat i lav kunde vi inte finna. Det högsta registrerade vårdet låg på 0,013 % nitrat-N i torrsubstans (tabell 1. Accumuleringen av nitrat i barris och kruståtel var också låg (tabell 2. De högsta värdena (0,05 % erhölls i ljung. Koncentrationerna låg klart under den nivå som kan bedömas vara skadlig fôr renen. Gödslingen gav ett mycket tydligt utslag på råproteinhalten i betesvåxterna. Detta gällde i synnerhet kruståtel. Fyra veckor efter gödsling med 150 kg N/ha hade råproteinhalten mer än fördubblats och låg på ca 20 % i torrsubstans (figur 2 och 3. Effekten av gödsling på råproteinhalten i den vissnade kruståteln p

Effects of reindeer density on vascular plant diversity on North Scandinavian mountains

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Johan Olofsson

2005-04-01

studerade hur renbete påverkar kärlväxtflorans artrikedom och diversitet på dolomitpåverkade lågalpina lokaler i de artrikaste delarna av norra Fennoskandien. Vi inventerade 8 lokaler med olika rentätheter. Två lokaler ligger inom Malla Nationalpark, där renar har varit förbjudna sedan 1981 och starkt begränsade sedan 1950-talet. De sex andra lokalerna ligger i andra artrika områden med samma dolomitdominerade berggrund, men är betade av renar. Rentätheterna vid de studerade lokalerna varierar från helt obefintligt till bland de högsta rentätheter man kan finna i Fennoskandien. Inventeringen utfördes genom att systematiskt undersöka fyra 2 m x 10 m stora ytor i varje lokal i en habitattyp som är speciellt rik i ovanliga kärlväxter (fjällsippehed-lågörtsäng komplex. Varje yta delades upp i 20 småytor (1 m x 1 m, och en total artlista upprättades för var och en av dessa småytor. Den första axeln i DCA (detrended correspondence analyses analysen korrelerade med rentätheten. Det visar att renar påverkar sammansättningen av växtsamhället. Ingen av de vanliga måtten på biodiversitet (artrikedom eller Shannon-Wiener diversitetsindex var korrelerade med rentätheten. Trots detta, var tätheterna av Ca-gynnade växter och arter rödlistade i Finland positivt korrelerade med rentätheten. Trots att renarna inte påverkade totala artrikedommen, kan de vara betydelsefulla för regionala biodiversiteten eftersom de gynnar ovanliga och hotade arter. De vanliga måtten på biodiversitet har begränsat värde för bevarandebiologiska frågeställningar, eftersom de är lika känsliga för ovanliga och vanliga arter.

Selected Abstracts of the 2nd Congress of joint European Neonatal Societies (jENS 2017; Venice (Italy; October 31-November 4, 2017; Session "Neonatal Infectious Diseases/Immunology"

Directory of Open Access Journals (Sweden)

--- Various Authors

2017-10-01

.F. Virupachi, R.A. KhanABS 18. CHARACTERIZATION OF RESISTANCE PLASMIDS DURING A NOSOCOMIAL EPE-OUTBREAK USING OPTICAL DNA MAPPING • S.K. Bikkarolla, V. Nordberg, M.H. Kabir, V. Müller, T. Ambjörnsson, C.G. Giske, L. Navér, L. Sandegren, F. WesterlundABS 19. NEONATAL INTESTINAL COLONIZATION WITH ESBL-PRODUCING ENTEROBACTERIACEAE – A 5 YEAR FOLLOW UP STUDY • V. Nordberg, K. Jonsson, C.G. Giske, A. Iversen, O. Aspevall, B. Jonsson, A. Camporeale, M. Norman, L. NavérABS 20. DNA VIRUSES: THEIR ROLE IN ACUTE RESPIRATORY INFECTIONS IN NEONATAL UNIT IN TUNISIA • I. Brini, N. Hannachi, A. Guerrero, B. Hetzer, W. Borena, S. Nouri Merchaoui, H. Sboui, D. Von Laer, J. Boukadida, H. StoiberABS 21. OUTCOMES OF CONGENITAL CYTOMEGALOVIRUS DISEASE FOLLOWING MATERNAL PRIMARY AND NON-PRIMARY INFECTION • A. Giannattasio, S. Cenni, D. De Martino, T. Ferrara, L. Capasso, E. Capone, P. Di Costanzo, F. RaimondiABS 22. LONG TERM FOLLOW UP OF HEARING DISORDERS IN PATIENTS WITH CONGENITAL CYTOMEGALOVIRUS INFECTION • A. Giannattasio, R. Alfani, P. Di Costanzo, D. Bruzzese, L. Bucci, M.R. Augurio, L. Capasso, F. RaimondiABS 23. REVIEW OF ADVERSE VACCINE REACTIONS IN AN IRISH NEONATAL UNIT • C. Fox, E. GordonABS 24. DOES DURATION OF BLOOD CULTURE REPORTING IMPACT ON THE CARE OF NEONATES AT RISK OF EARLY ONSET NEONATAL SEPSIS? • L. Woodgate, C. Chetcuti GanadoABS 25. A CANDIDA TROPICALIS OUTBREAK DURING EL NIÑO IN A NEONATAL INTENSIVE CARE UNIT IN SOUTHERN PHILIPPINES • C. Masilungan, R. Aunal, J. PeraltaABS 26. CONGENITAL CYTOMEGALOVIRUS INFECTION – NEONATAL ASPECT • S. Stefanovic, V. Stefanovic, V. StefanovicABS 27. DIAGNOSTIC VALUE OF SERUM AMYLOID A IN NEONATAL BACTERIAL INFECTIONS AND ASSOCIATIONS WITH CIRCULATING HIGH DENSITY LIPOPROTEIN (HDL AND CYTOKINE LEVELS • V. Bourika, E. Hantzi, A. Margeli, I. Papassotiriou, T. SiahanidouABS 28. CONGENITAL TUBERCULOSIS AS A RESULT OF DISSEMINATED MATERNAL DISEASE. IS CORRECT THE ACTUAL MANAGEMENT? • A.B. Escobar Izquierdo, G. Ucl

Reindeer meat – is it always tender, tasty and healthy?

Directory of Open Access Journals (Sweden)

Eva Wiklund

2007-04-01

PUFA och särskilt de sk. omega-3 PUFA. En tränad smakpanel bedömde att kött från renar som utfodrats med kommersiellt renfoder smakade mer lever och sött och hade mindre bismaker (som t.ex. gräs, vilt och ren jämfört med kött från naturbetande renar. I en konsumentundersökning av samma typer av renkött föredrog 50 procent av konsumenterna beteskött och 50 procent föredrog kött från utfodrade renar.Den senaste forskningen har studerat nya foderblandningar där ingredienser som linfrö och fiskmjöl har utvärderats. Linfrökaka som tillsats i renpellets gav köttet en fettsammansättning som påminde om den i kött från naturbetande renar, d.v.s. köttet innehöll mer PUFA än kött från renar som utfodrats med normala pellets. I försök där fiskmjöl har använts som proteintillskott i renfoder visades ett bra foderutnyttjande och god tillväxt hos renarna och inga negativa effekter på renköttets smak kunde påvisas varken av en tränad smakpanel eller vid en konsumentundersökning. Fettsammansättningen i köttet påverkades marginellt av tillsatsen av fiskmjöl jämfört med normalfodret baserat på sojaprotein. Kött från kontrollgruppen av naturbetande renar hade det signifikant högsta innehållet av PUFA. Kunskapen om de olika faktorer som påverkar renköttets kvalitet har ökat påtagligt under de senaste 25 åren, men fortfarande saknas en del fakta när det gäller sambanden mellan produktionssystem, slakthantering och köttkvalitet.

Blood composition of the reindeer. I. Haematology

Directory of Open Access Journals (Sweden)

Mauri Nieminen

1981-05-01

Cl-losning av 0,71% och var total vid 0,37%. De relativa proportionerna av neutrofil-, eosinofil- och basofilgranulocyter samt av agranulåra lymfocyter var respektive 52, 5, 2, 42 och 2%. Renarnas kalvning sker utan synbar blodning. Hos gravida renkor sjånk mångden av roda blodkroppar såsom hemomglobin och hematokrit. Den under den forstå tiden av kalvarnas amning forekommande relativa anemin beror emellertid på jårnbrist och eventuellt också på splittring av de fetala erotrocyterna. Hos fritt betande vuxna renkor var foljande vården som hogst under sommaren och hosten och sjonk under vintern: medelkroppsvikt (50-70 kg, mångden av roda blodkroppar (8-11 x 1012/l, hemoglobin (118-185 g/l, hematrokrit (42-51%, vita blodkroppar (6-10 x 109/l, erytrocytsånkan och serumjårnhalt (23-54 micromol/l. De lågsta medelvården mattes tidigt på våren hos fastande renkor. Kroppsvikten och blodets hematologiska vården var hoga hos sådana renkor, vilka om vintern matats med ensilage eller melasse.  

The 15th Biannual National Congress of the South African Society of Psychiatrists, 10-14 August 2008, Fancourt, George, W Cape

Directory of Open Access Journals (Sweden)

Eugene Allers

2008-08-01

and body Oye Gureje 15. Child and adolescent psychopharmacology: Current trends and complexities S M Hawkridge 16. Integrating mental illness, suicide and religion Volker Hitzeroth 17. Cost of acute inpatient mental health care in a 72-hour assessment uniy A B R Janse van Rensburg, W Jassat 18. Management of Schizophrenia according to South African standard treatment guidelines A B R Janse van Rensburg 19. Structural brain imaging in the clinical management of psychiatric illness F Y Jeenah 20. ADHD: Change in symptoms from child to adulthood S A Jeeva, A Turgay 21. HIV-Positive psychiatric patients in antiretrovirals G Jonsson, F Y Jeenah, M Y H Moosa 22. A one year review of patients admitted to tertiary HIV/Neuropsychiatry beds in the Western Cape John Joska, Paul Carey, Ian Lewis, Paul Magni, Don Wilson, Dan J Stein 23. Star'd - Critical review and treatment implications Andre Joubert 24. Options for treatment-resistent depression: Lessons from Star'd; an interactive session Andre Joubert 25. My brain made me do it: How Neuroscience may change the insanity defence Sean Kaliski 26. Child andadolescent mental health services in four African countries Sharon Kleintjies, Alan Flisher, Victoruia Campbell-Hall, Arvin Bhana, Phillippa Bird, Victor Doku, Natalie, Drew, Michelle Funk, Andrew Green, Fred Kigozi, Crick Lund, Angela Ofori-Atta, Mayeh Omar, Inge Petersen, Mental Health and Poverty Research Programme Consortium 27. Individualistic theories of risk behaviour Liezl Kramer, Volker Hitzeroth 28. Development and implementation of mental health poliy and law in South Africa: What is the impact of stigma? Ritsuko Kakuma, Sharon Kleintjes, Crick Lund, Alan J Flisher, Paula Goering, MHaPP Research Programme Consortium 29. Factors contributing to community reintegration of long-term mental health crae users of Weskoppies Hospital Carri Lewis, Christa Kruger 30. Mental health and poverty: A systematic review of the research in low- and middle-income countries Crick Lund

Persistent Neck and Shoulder Pains among Computer Office Workers: A Longitudinal Study

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Farideh Sadeghian

2012-11-01

S, Gray A. Prevalence and impact of musculoskeletal disorders in New Zealand nurses, postal workers and office workers. Aust N Z J Public Health 2009;33(5:437-41. 14. Eltayeb S, Staal JB, Hassan A, de Bie RA. Work Related Risk Factors for Neck, Shoulder and Arms Complaints: A Cohort Study Among Dutch Computer Office Workers. J Occup Rehabil 2009;19(4:315-22. 15. Lassen CF, Mikkelsen S, Kryger AI, Anders JH. Risk factors for persistent elbow, forearm and hand pain among computer workers. Scand J Work Environ Health 2005;31(2:122-31. 16. Coggon D. Occupational medicine at a turning point. Occup Environ Med 2005;62(5:281-3. 17. Kuorinka I, Jonsson B, Kilbom A, Vinterberg H, Biering-Sørensen F, Andersson G, et al. Standardised Nordic questionnaires for the analysis of musculoskeletal symptoms. Appl Ergon 1987;18(3:233-7. 18. Iwakiri K, Mori I, Sotoyama M, Horiguchi K, Ochiai T, Jonai H, et al. [Survey on visual and musculoskeletal symptoms in VDT workers]. Sangyo Eiseigaku Zasshi 2004;46(6:201-12. (Full Text in Japanese 19. Choobineh A, Nouri E, Arjmandzadeh A, Mohamadbaigi A. Musculoskeletal Disorders among Bank Computer Operators. Iran Occup Health 2006;3(3,4:12-7. 20. Tornqvist EW, Kilbom Å, Vingård E, Alfredsson L, Hagberg M, Theorell T, et al. The influence on seeking care because of neck and shoulder disorders from work-related exposures. Epidemiology 2001;12(5:537-45. 21. Andersen JH, Kaergaard A, Frost P, Thomsen JF, Bonde JP, Fallentin N, et al. Physical, psychosocial, and individual risk factors for neck shoulder pain with pressure tenderness in the muscles among workers performing monotonous, repetitive work. Spine 2002;27(6:660-7. 22. Kaergaard A, Andersen JH. Musculoskeletal disorders of theneck and shoulders in female sewing machine operators: prevalence, incidence, and prognosis. Occup Environ Med. 2000;57(8:528-34. 23. Miranda H, Viikari-Juntura E, Martikainen R, Riihimäki H. A prospective study on knee pain and its risk factors. Osteoarthritis

Blood composition of the reindeer . II. Blood chemistry

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Mauri Nieminen

1983-05-01

uppnådde nivån hos en vuxen ren vid 5 månaders ålder (respektive medeltal 5,1 g/1, 0,4 mmol/1, 2,7 mmol. Halterna av kolesterol, fettsyra, myristinsyra och palmitinsyra var hogre i kalvarnas serum, emedan halterna av stearinsyra och oljesyra var lagre ån hos vajor. Under de forstå levnadsdygnen producerar kalven katekolaminer i rikliga mångder. Dåremot år serumdopamid - B - hydroxylas-aktiviteten ganska låg. En fritt betande vajas blodsockerhalt (3,4 - 4,6 mmol/1, totalåggvitehalt i serum (63 - 87 g/1, albuminhalt (39 - 43 g/1, globulinhalt (23 - 44 g/1, urea (5,7- 9 mmol/1, totala lipidhalt (2,7 - 5,2 g/1, triglyceridhalt (0,17-0,33 mmol/1, fettsyrehalt (0,89 - 1,54 g/1, kalciumhalt (2,2 - 2,6 mmol/1, fosforhalt (1,6 - 2,2 mmol/1, magnesiumhalt (0,8 - 1,2 mmol/1 och kopparhalt (6,7 - 17 Jmol/l var hogst under sommaren och hosten emedan de sjonk under vintern. De lågsta halterna mattes hos u-tsvultna vajor på våren. Den hoga ureahalten i serum samt CPK-, LDH- och SAP-aktiviteterna återspeglar åggviteåmnens och våvnaders upplosning i kroppen. Årstiderna och nåringen inverkade varken på halterna av T4 kreatinin, natrium eller klorid i serum. De hoga siffrorna for kroppsvikt och blodets kemiska varden mattes hos vajor som under vintersåsongen matats med pressfoder och melassflis.

Selected Abstracts of the 2nd Congress of joint European Neonatal Societies (jENS 2017; Venice (Italy; October 31-November 4, 2017; Session "Quality Improvement, Parents Centered Care"

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--- Various Authors

2017-10-01

ASSESSMENT IN A NEONATAL UNIT FOLLOWING A PLAN TO IMPROVE PATIENT SAFETY • M. Arriaga-Redondo, A. Rodriguez-Sanchez de la Blanca, E. Sanz-Lopez, A. Diaz-Redondo, R. Gregorio-Hernandez, P. Chimenti-Camacho, M. Sanchez-LunaABS 56. SHORT AND LONG TERM OUTCOMES RELATED TO UMBILICAL VENOUS CATHETER PLACEMENT IN PRETERM INFANTS • L. Arques, R. del Rio, C. Balcells, E. Inarejos, V. Aldecoa-Bilbao, I. Iglesias-PlatasABS 57. ACHIEVING NORMOTHERMIA IN INFANTS ADMITTED TO THE NEONATOLOGY DE­PARTMENT – A QUALITY IMPROVEMENT PROJ­ECT AT THE KAROLINSKA UNIVERSITY HOSPITAL • K. Jonsson, A. Gudmundsdottir, A. Chakhunashvili, A.-S. Ingman, C. Branvik-Ingelsson, E. Wilson, I. Edqvist, M. Viberg, B. Hallberg, M. BreindahlABS 58. PERSONALITY TRAITS AND STYLES OF COPING WITH STRESS AMONG MIDWIVES • B. Zych, W. Blaz, M. Muster, M. Mazur-Magoła, G. RabaABS 59. EVALUATING MATERNAL CLOSENESS AND SEPARATION IN NICU. GUIDELINES FOR THE CREATION OF PERINATAL CENTERS • A. Karkani, K. Konstadinidi, M. Theodoraki, S. Gancheva, M. PapadopoulouABS 60. CURRENT PARENT FEEDBACK RESPONSE RATES AND FEEDBACK METHODS IN NEONATAL TRANSPORT SERVICE ACROSS THE UK • P. Bhat, D. Winderbank-Scott, C. Garland, L. Watts, C. Leach, A. Frame, G. Bullimore, C. LawnABS 61. ENHANCING NEONATAL AND PARENTAL OUTCOMES THROUGH THE OPTIMIZATION OF EVIDENCE-BASED NURSING PRACTICES • M. Aita, S. Semenic, N. Feeley, L. Haiek, M. Héon, A. Larone Juneau, K. Levasseur, G. Roch, L. Talbot

The 12th Edition of the Scientific Days of the National Institute for Infectious Diseases “Prof. Dr. Matei Bals” and the 12th National Infectious Diseases Conference

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Cristian-Mihail Niculae

2016-11-01

-Kezdi, Cristina Gîrbovan, Andrea Incze, Anca Meda Georgescu A54 LPS serum levels and correlation with immunological, virological and clinical outcome in HIV infected patients Simona Alexandra Iacob, Diana Gabriela Iacob, Eugenia Panaitescu, Monica Luminos, Manole Cojocaru A55 LL37 human cathelicidin serum levels are positively correlated with IFN gamma and alanine aminotransferase level in HCV infection Simona Alexandra Iacob, Diana Gabriela Iacob, Monica Luminos A56 Early diagnosis of pulmonary tuberculosis in a non-compliant HIV/AIDS late presenter patient Vochita Laurențiu, Vochita Andreia, Opreanu Radu, Trinca Bogdan, Rosca Ovidiu, Marincu Iosif A57 Evolution of antiretroviral regimens in naϊve patients in 2016 Ramona Zamfir, Alina Angelescu, Alena Andreea Popa, Raluca Jipa, Ruxandra Moroti, Adriana Hristea, Liana Gavriliu, Șerban Benea, Elisabeta Benea A58 The unfavorable risk factors for HIV infected persons with positive blood cultures hospitalized at the National Institute for Infectious Diseases “Prof. Dr. Matei Balș” in 2015 Alena-Andreea Popa, Georgeta Ducu, Daniela Camburu, Alina Cozma, Manuela Podani, Roxana Dumitriu, Liana Gavriliu, Șerban Benea, Elisabeta Benea A59 Epidemiological aspects of HIV infection in Oltenia region Andreea Cristina Stoian, Florentina Dumitrescu, Augustin Cupșa, Lucian Giubelan, Irina Niculescu, Loredana Ionescu, Livia Dragonu A60 HIV risk behaviors and prevalence among patients in methadone maintenance therapy (MMT from Arena center, Bucharest Adrian Octavian Abagiu, Loredana Nicoleta Stoica, Catrinel Blaga, Archontis Koulosousas, Roxana Ștefănescu, Alice Atomoaie, Florentina Paraschiv, Florin Matache Duna A61 Therapeutic options in a case of severe psoriasis associated with both HIV infection and hepatitis C virus previously treated with fumaric acid esters Rodica Olteanu, Roxana Ion, Alexandra Zota, Isra Ennour Jaballah, Lara Mahfoud, Georgeta Preda, Magda Constantin A62 Prevalence of autoantibodies against gangliosides in

Selected Abstracts of the 1st Congress of joint European Neonatal Societies (jENS 2015; Budapest (Hungary; September 16-20, 2015; Session “Pulmonology”

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Various Authors

2015-09-01

. Lopriore, A.B. te PasABS 7. CORRELATION AND INTERCHANGEABILITY OF VENOUS AND CAPILLARY BLOOD GASES FOR MONITORING GAS EXCHANGE IN THE NEONATAL INTENSIVE CARE UNIT • R. Tan, S. Pauws, M van Biemen, E. Lopriore, A. te PasABS 8. ALTERATION OF TONIC GABAERGIC INHIBITION ON CONTROL OF BREATHING IN 12 DAYS OLD RATS CHRONICALLY TREATED WITH CAFFEINE • N. Uppari, V. Joseph, A. BairamABS 9. DIAPHRAGMATIC FUNCTION BEFORE AND AFTER APPLICATION OF EXTERNAL INSPIRATORY LOADING IN PRETERM AND TERM INFANTS • G. Dimitriou, S. Fouzas, A. Vervenioti, P. PelekoudaABS 10. PROGESTERONE DECREASES VENTILATION AND ENHANCES APNEA IN DEVELOPING RATS CHRONICALLY TREATED WITH CAFFEINE • N. Uppari, V. Joseph, A. BairamABS 11. A RANDOMISED FEASIBILITY TRIAL AND IN-VITRO PERFORMANCE OF A NEW SYSTEM FOR RESPIRATORY SUPPORT DURING INITIAL STABILISATION OF PRETERM INFANTS • S. Donaldsson, T. Drevhammar, L. Taittonen, S. Klemming, B. JonssonABS 12. USE OF A RESUSCITATION TRAINING APP SIGNIFICANTLY IMPROVES HEART RATE ASSESSMENT DURING NEWBORN SIMULATION • S. Coleman, C. Henry, E. Murphy, P. Blanchfield, M. Ismat, P. Okhiria, C. Tamakloe, D. SharkeyABS 13. DOES THE BAG-VALVE-MASK VENTILATION TECHNIQUE (2-FINGER VS. 5-FINGER-TECHNIQUE OR THE GLOVE SIZE OF HEALTH CARE PROVIDERS AFFECT TIDAL VOLUME DURING SIMULATED NEONATAL RESUSCITATION? • H. Kilbertus, B. Urlesberger, B. SchwabergerABS 14. ACCURACY OF CURRENT AVAILABLE NEONATAL RESPIRATORY FUNCTION MONITORS DURING NEONATAL RESUSCITATION • C. Verbeek, H.A. van Zanten, J.J. van Vonderen, E.W. van Zwet, S.B. Hooper, A.B. te PasABS 15. OROPHARYNGEAL AIRWAY TO ASSIST VENTILATION OF PRETERM INFANTS IN THE DELIVERY ROOM • C. Kamlin, G. Schmoelzer, J. Dawson, L. McGrory, J O’Shea, P. DavisABS 16. RESPIRATORY MORBIDITY OF PRETERM INFANTS WITH AND WITHOUT BRONCHOPULMONARY DYSPLASIA, AFTER DISCHARGE, IN THE FIRST 2 YEARS OF LIFE • E. Mulder, M. Rijken, L. de Smet, E. Lopriore, A. te PasABS 17. 10 YEAR OUTCOMES OF CONGENITAL DIAPHRAGMATIC HERNIA IN