Expression of ABCG2 and Bmi-1 in oral potentially malignant lesions and oral squamous cell carcinoma

International Nuclear Information System (INIS)

Dalley, Andrew J; Pitty, Luke P; Major, Aidan G; AbdulMajeed, Ahmad A; Farah, Camile S

2014-01-01

Early diagnosis is vital for effective treatment of oral squamous cell carcinoma (OSCC). The optimal time for clinical intervention is prior to malignancy when patients present with oral potentially malignant lesions such as leukoplakia or erythroplakia. Transformation rates for oral dysplasia vary greatly and more rigorous methods are needed to predict the malignant potential of oral lesions. We hypothesized that the expression of two putative stem cell markers, ABCG2 and Bmi-1, would correlate with disease severity for non diseased, potentially malignant and OSCC specimens and cell lines derived from an equivalent range of tissues. We compared immunoreactive protein and relative gene expression of ABCG2 and Bmi-1 in eight cell lines derived from source tissues ranging in disease severity from normal (OKF6-TERT2) through mild and moderate/severe dysplasia (DOK, POE-9n) to OSCC (PE/CA-PJ15, SCC04, SCC25, SCC09, SCC15). We also analyzed immunoreactive protein expression of ABCG2 and Bmi-1 in 189 tissue samples with the same range of disease severity. A trend between oral lesion severity to ABCG2 and Bmi-1 immunostain intensity was observed. Flow cytometry of oral cell lines confirmed this trend and gave good correlation with RT-PCR results for ABCG2 (r = 0.919, P = 0.001; Pearson) but not Bmi-1 (r = −0.311). The results provide evidence of increased density of ABCG2 and Bmi-1-positive populations in malignant and oral potentially malignant lesions and derived cell lines, but that intragroup variability within IHC, flow cytometry, and RT-PCR results compromise the diagnostic potential of these techniques for discriminating oral dysplasia from normal tissue or OSCC

Brain and Testis Accumulation of Regorafenib is Restricted by Breast Cancer Resistance Protein (BCRP/ABCG2) and P-glycoprotein (P-GP/ABCB1).

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Kort, Anita; Durmus, Selvi; Sparidans, Rolf W; Wagenaar, Els; Beijnen, Jos H; Schinkel, Alfred H

2015-07-01

Regorafenib is a novel multikinase inhibitor, currently approved for the treatment of metastasized colorectal cancer and advanced gastrointestinal stromal tumors. We investigated whether regorafenib is a substrate for the multidrug efflux transporters ABCG2 and ABCB1 and whether oral availability, brain and testis accumulation of regorafenib and its active metabolites are influenced by these transporters. We used in vitro transport assays to assess human (h)ABCB1- or hABCG2- or murine (m)Abcg2-mediated active transport at high and low concentrations of regorafenib. To study the single and combined roles of Abcg2 and Abcb1a/1b in oral regorafenib disposition and the impact of Cyp3a-mediated metabolism, we used appropriate knockout mouse strains. Regorafenib was transported well by mAbcg2 and hABCG2 and modestly by hABCB1 in vitro. Abcg2 and to a lesser extent Abcb1a/1b limited brain and testis accumulation of regorafenib and metabolite M2 (brain only) in mice. Regorafenib oral availability was not increased in Abcg2(-/-);Abcb1a/1b(-/-) mice. Up till 2 h, metabolite M5 was undetectable in plasma and organs. Brain and testis accumulation of regorafenib and brain accumulation of metabolite M2 are restricted by Abcg2 and Abcb1a/1b. Inhibition of these transporters may be of clinical relevance for patients with brain (micro)metastases positioned behind an intact blood-brain barrier.

Novel understanding of ABC transporters ABCB1/MDR/P-glycoprotein, ABCC2/MRP2, and ABCG2/BCRP in colorectal pathophysiology

DEFF Research Database (Denmark)

Andersen, Vibeke; Svenningsen, Katrine; Knudsen, Lina Almind

2015-01-01

transporter proteins, inflammatory bowel disease, ulcerative, colitis, Crohns disease, colorectal cancer, colitis, intestinal inflammation, intestinal carcinogenesis, ABCB1/P-glycoprotein (P-gp/CD243/MDR1), ABCC2/multidrug resistance protein 2 (MRP2) and ABCG2/breast cancer resistance protein (BCRP), Abcb1....../Mdr1a, abcc2/Mrp2, abcg2/Bcrp, knock-out mice, tight junction, membrane lipid function. RESULTS: Recently, human studies reported that changes in the levels of ABC transporters were early events in the adenoma-carcinoma sequence leading to CRC. A link between ABCB1, high fat diet and gut microbes...

Effect of polymorphisms in the ABCG2, LEPR and SCD1 genes on ...

African Journals Online (AJOL)

Sahand Rayaneh

2016-06-24

Jun 24, 2016 ... Abstract. This study was performed to investigate the association between polymorphisms in the ABCG2 (ATP- binding cassette sub-family G member 2), LEPR (leptin receptor) and SCD1 (stearoyl-coenzyme A desaturase 1) genes and milk production traits in Holstein dairy cows in Iran. The analysis was ...

Transcriptome Comparative Profiling of Barley eibi1 Mutant Reveals Pleiotropic Effects of HvABCG31 Gene on Cuticle Biogenesis and Stress Responsive Pathways

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Eviatar Nevo

2013-10-01

Full Text Available Wild barley eibi1 mutant with HvABCG31 gene mutation has low capacity to retain leaf water, a phenotype associated with reduced cutin deposition and a thin cuticle. To better understand how such a mutant plant survives, we performed a genome-wide gene expression analysis. The leaf transcriptomes between the near-isogenic lines eibi1 and the wild type were compared using the 22-k Barley1 Affymetrix microarray. We found that the pleiotropic effect of the single gene HvABCG31 mutation was linked to the co-regulation of metabolic processes and stress-related system. The cuticle development involved cytochrome P450 family members and fatty acid metabolism pathways were significantly up-regulated by the HvABCG31 mutation, which might be anticipated to reduce the levels of cutin monomers or wax and display conspicuous cuticle defects. The candidate genes for responses to stress were induced by eibi1 mutant through activating the jasmonate pathway. The down-regulation of co-expressed enzyme genes responsible for DNA methylation and histone deacetylation also suggested that HvABCG31 mutation may affect the epigenetic regulation for barley development. Comparison of transcriptomic profiling of barley under biotic and abiotic stresses revealed that the functions of HvABCG31 gene to high-water loss rate might be different from other osmotic stresses of gene mutations in barley. The transcriptional profiling of the HvABCG31 mutation provided candidate genes for further investigation of the physiological and developmental changes caused by the mutant.

Cellular Cholesterol Regulates Ubiquitination and Degradation of the Cholesterol Export Proteins ABCA1 and ABCG1*

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Hsieh, Victar; Kim, Mi-Jurng; Gelissen, Ingrid C.; Brown, Andrew J.; Sandoval, Cecilia; Hallab, Jeannette C.; Kockx, Maaike; Traini, Mathew; Jessup, Wendy; Kritharides, Leonard

2014-01-01

The objective of this study was to examine the influence of cholesterol in post-translational control of ABCA1 and ABCG1 protein expression. Using CHO cell lines stably expressing human ABCA1 or ABCG1, we observed that the abundance of these proteins is increased by cell cholesterol loading. The response to increased cholesterol is rapid, is independent of transcription, and appears to be specific for these membrane proteins. The effect is mediated through cholesterol-dependent inhibition of transporter protein degradation. Cell cholesterol loading similarly regulates degradation of endogenously expressed ABCA1 and ABCG1 in human THP-1 macrophages. Turnover of ABCA1 and ABCG1 is strongly inhibited by proteasomal inhibitors and is unresponsive to inhibitors of lysosomal proteolysis. Furthermore, cell cholesterol loading inhibits ubiquitination of ABCA1 and ABCG1. Our findings provide evidence for a rapid, cholesterol-dependent, post-translational control of ABCA1 and ABCG1 protein levels, mediated through a specific and sterol-sensitive mechanism for suppression of transporter protein ubiquitination, which in turn decreases proteasomal degradation. This provides a mechanism for acute fine-tuning of cholesterol transporter activity in response to fluctuations in cell cholesterol levels, in addition to the longer term cholesterol-dependent transcriptional regulation of these genes. PMID:24500716

Hedgehog Pathway Inhibitor HhAntag691 Is a Potent Inhibitor of ABCG2/BCRP and ABCB1/Pgp

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Yimao Zhang

2009-01-01

Full Text Available HhAntag691 (GDC-0449, a low-molecular weight inhibitor of the tumor-promoting hedgehog (Hh signaling pathway, has been used to treat medulloblastoma in animal models and has recently entered clinical trials for a variety of solid tumors. Here, we show that HhAntag691 inhibits multiple ATP-binding cassette (ABC transporters. ATP-binding cassette transporters are within a family of membrane proteins, the overexpression of which is associated with multidrug resistance, a major impediment to successful cancer treatment. HhAntag691 is a potent inhibitor of two ABC transporters, ABCG2/BCRP and ABCB1/Pgp, and is a mild inhibitor of ABCC1/MRP1. In ABCG2-overexpressing HEK293 cells, HhAntag691 increased retention of the fluorescent ABCG2 substrate BODIPY-prazosin and resensitized these cells to mitoxantrone, an antineoplastic ABCG2 substrate. In Madin-Darby canine kidney II cells engineered to overexpress Pgp or MRP1, HhAntag691 increased the retention of calcein-AM and resensitized them to colchicine. HhAntag691 also resensitized human non-small cell lung carcinoma cells NCI-H460/par and NCI-H460/MX20, which overexpress ABCG2 in response to mitoxantrone, to mitoxantrone, and to topotecan or SN-38. The IC50 values of HhAntag691 for inhibition of ABCG2 and Pgp were ∼1.4 and ∼3.0 µM, respectively. Because ABC transporters are highly expressed at the blood-brain barrier and on many tumor cells, they contribute significantly to treatment failure of many types of cancer, particularly of those within the neuraxis. In addition to its effect on Hh signaling, the ability of HhAntag691 and related compounds to inhibit two key ABC transporters could contribute to their effectiveness in treating malignancies.

DGAT1 and ABCG2 polymorphism in Indian cattle (Bos indicus and buffalo (Bubalus bubalis breeds

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Mishra Bina

2006-11-01

Full Text Available Abstract Background Indian cattle (Bos indicus and riverine buffalo (Bubalus bubalis give a poor yield of milk but it has a high fat and protein percentage compared to taurine cattle. The identification of QTLs (Quantitative Trait Loci on BTA14 and BTA6 and its subsequent fine mapping has led to identification of two non conservative mutations affecting milk production and composition. Our objective was to estimate the frequency of K232A (DGAT1 – diacylglycerol – acyltransferase 1 and Y581S (ABCG2 – ATP binding cassette sub family G member 2 polymorphisms in diverse cattle and buffalo breeds of India having large variation in terms of milk production. Results We screened the reported missense mutations in six cattle and five buffalo breeds. The DGAT1K and ABCG2Y alleles were found to be fixed in Indian cattle and buffalo breeds studied. Conclusion This study provides an indirect evidence that all the Indian cattle and buffalo breeds have fixed alleles with respect to DGAT1 and ABCG2 genes reported to be responsible for higher milk fat yield, higher fat and protein percent.

Novel understanding of ABC transporters ABCB1/MDR/P-glycoprotein, ABCC2/MRP2, and ABCG2/BCRP in colorectal pathophysiology

DEFF Research Database (Denmark)

Andersen, Vibeke; Svenningsen, Katrine; Almind Knudsen, Lina

2015-01-01

AIM: To evaluate ATP-binding cassette (ABC) transporters in colonic pathophysiology as they had recently been related to colorectal cancer (CRC) development. METHODS: Literature search was conducted on PubMed using combinations of the following terms: ABC transporters, ATP binding cassette...... with glucocorticoids. The evidence for the involvement of ABCC2 and ABCG2 in colonic pathophysiology was weak. CONCLUSION: ABCB1, diet, and gut microbes mutually interact in colonic inflammation, a well-known risk factor for CRC. Further insight may be translated into preventive and treatment strategies....... transporter proteins, inflammatory bowel disease, ulcerative, colitis, Crohns disease, colorectal cancer, colitis, intestinal inflammation, intestinal carcinogenesis, ABCB1/P-glycoprotein (P-gp/CD243/MDR1), ABCC2/multidrug resistance protein 2 (MRP2) and ABCG2/breast cancer resistance protein (BCRP), Abcb1...

DNA methylation of loci within ABCG1 and PHOSPHO1 in blood DNA is associated with future type 2 diabetes risk

DEFF Research Database (Denmark)

Dayeh, Tasnim; Tuomi, Tiinamaija; Almgren, Peter

2016-01-01

Identification of subjects with a high risk of developing type 2 diabetes (T2D) is fundamental for prevention of the disease. Consequently, it is essential to search for new biomarkers that can improve the prediction of T2D. The aim of this study was to examine whether 5 DNA methylation loci...... muscle from diabetic vs. non-diabetic subjects. DNA methylation at the ABCG1 locus cg06500161 in blood DNA was associated with an increased risk for future T2D (OR = 1.09, 95% CI = 1.02-1.16, P-value = 0.007, Q-value = 0.018), while DNA methylation at the PHOSPHO1 locus cg02650017 in blood DNA...... was associated with a decreased risk for future T2D (OR = 0.85, 95% CI = 0.75-0.95, P-value = 0.006, Q-value = 0.018) after adjustment for age, gender, fasting glucose, and family relation. Furthermore, the level of DNA methylation at the ABCG1 locus cg06500161 in blood DNA correlated positively with BMI, HbA1c...

Lentivirus-ABCG1 instillation reduces lipid accumulation and improves lung compliance in GM-CSF knock-out mice

International Nuclear Information System (INIS)

Malur, Anagha; Huizar, Isham; Wells, Greg; Barna, Barbara P.; Malur, Achut G.; Thomassen, Mary Jane

2011-01-01

but improved significantly after lenti-ABCG1 treatment. Data demonstrate that in vivo instillation of lenti-ABCG1 in GM-CSF KO mice is sufficient to restore pulmonary homeostasis by: (1) upregulating ABCG1; (2) reducing intra and extracellular lipids; and (3) improving lung function. Results suggest that the ABCG1 lipid transporter is the key downstream target of GM-CSF-induced PPARγ necessary for surfactant catabolism.

Lentivirus-ABCG1 instillation reduces lipid accumulation and improves lung compliance in GM-CSF knock-out mice

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Malur, Anagha; Huizar, Isham [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Wells, Greg [Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States); Barna, Barbara P. [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Malur, Achut G. [Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States); Thomassen, Mary Jane, E-mail: thomassenm@ecu.edu [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States)

2011-11-18

analysis of bronchoalveolar lavage fluid. Lung compliance was diminished in untreated GMCSF KO mice but improved significantly after lenti-ABCG1 treatment. Data demonstrate that in vivo instillation of lenti-ABCG1 in GM-CSF KO mice is sufficient to restore pulmonary homeostasis by: (1) upregulating ABCG1; (2) reducing intra and extracellular lipids; and (3) improving lung function. Results suggest that the ABCG1 lipid transporter is the key downstream target of GM-CSF-induced PPAR{gamma} necessary for surfactant catabolism.

Upregulated miR-132 in Lgr5+ gastric cancer stem cell-like cells contributes to cisplatin-resistance via SIRT1/CREB/ABCG2 signaling pathway.

Science.gov (United States)

Zhang, Lanfang; Guo, Xiaohe; Zhang, Dezhong; Fan, Yingying; Qin, Lei; Dong, Shuping; Zhang, Lanfang

2017-09-01

Cisplatin resistance has long been a major problem that restricts its use. A novel paradigm in tumor biology suggests that gastric tumor chemo-resistance is driven by gastric cancer stem cell-like (GCSCs). Growing evidence has indicated that microRNAs (miRNAs) contributes to chemo-resistance in gastric cancer (GC). Here, Lgr5 + cells derived from gastric cancer cell lines displayed stem cell-like features. Flow cytometry demonstrated the presence of a variable fraction of Lgr5 in 19 out of 20 GC specimens. By comparing the miRNA expression profiles of Lgr5 + GCSCs and Lrg5 - cells, we established the upregulation of miR-132 in Lgr5 + GCSCs. The enhanced miR-132 expression correlated chemo-resistance in GC patients. Kaplan-Meier survival curve showed that patients with low miR-132 expression survived obviously longer. Functional assays results indicated that miR-132 promoted cisplatin resistance in Lgr5 + GCSCs in vitro and in vivo. Further dual-luciferase reporter gene assays revealed that SIRT1 was the direct target of miR-132. The expression of miR-132 was inversely correlated with SIRT1 in gastric cancer specimens. Furthermore, through PCR array we discovered ABCG2 was one of the downstream targets of SIRT1. Overexpression of SIRT1 down-regulated ABCG2 expression by promoting the de-acetylation of the transcription factor CREB. CREB was further activated ABCG2 via binding to the promoter of ABCG2 to induce transcription. Thus, we concluded that miR-132 regulated SIRT1/CREB/ABCG2 signaling pathway contributing to the cisplatin resistance and might serve as a novel therapeutic target against gastric cancer. © 2017 Wiley Periodicals, Inc.

Cholesterol Transporters ABCA1 and ABCG1 Gene Expression in Peripheral Blood Mononuclear Cells in Patients with Metabolic Syndrome

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Zahra Tavoosi

2015-01-01

Full Text Available ABCA1 and ABCG1 genes encode the cholesterol transporter proteins that play a key role in cholesterol and phospholipids homeostasis. This study was aimed at evaluating and comparing ABCA1 and ABCG1 genes expression in metabolic syndrome patients and healthy individuals. This case-control study was performed on 36 patients with metabolic syndrome and the same number of healthy individuals in Hamadan (west of Iran during 2013-2014. Total RNA was extracted from mononuclear cells and purified using RNeasy Mini Kit column. The expression of ABCA1 and ABCG1 genes was performed by qRT-PCR. Lipid profile and fasting blood glucose were measured using colorimetric procedures. ABCG1 expression in metabolic syndrome patients was significantly lower (about 75% compared to that of control group, while for ABCA1 expression, there was no significant difference between the two studied groups. Comparison of other parameters such as HDL-C, FBS, BMI, waist circumference, and systolic and diastolic blood pressure between metabolic syndrome patients and healthy individuals showed significant differences (P<0.05. Decrease in ABCG1 expression in metabolic syndrome patients compared to healthy individuals suggests that hyperglycemia, related metabolites, and hyperlipidemia over the transporter capacity resulted in decreased expression of ABCG1. Absence of a significant change in ABCA1 gene expression between two groups can indicate a different regulation mechanism for ABCA1 expression.

AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment

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Ming Lei

2016-02-01

Full Text Available The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata.

E1AF degradation by a ubiquitin-proteasome pathway

International Nuclear Information System (INIS)

Takahashi, Akiko; Higashino, Fumihiro; Aoyagi, Mariko; Yoshida, Koichi; Itoh, Miyuki; Kobayashi, Masanobu; Totsuka, Yasunori; Kohgo, Takao; Shindoh, Masanobu

2005-01-01

E1AF is a member of the ETS family of transcription factors. In mammary tumors, overexpression of E1AF is associated with tumorigenesis, but E1AF protein has hardly been detected and its degradation mechanism is not yet clear. Here we show that E1AF protein is stabilized by treatment with the 26S protease inhibitor MG132. We found that E1AF was modified by ubiquitin through the C-terminal region and ubiquitinated E1AF aggregated in nuclear dots, and that the inhibition of proteasome-activated transcription from E1AF target promoters. These results suggest that E1AF is degraded via the ubiquitin-proteasome pathway, which has some effect on E1AF function

Icotinib antagonizes ABCG2-mediated multidrug resistance, but not the pemetrexed resistance mediated by thymidylate synthase and ABCG2.

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Wang, De-Shen; Patel, Atish; Shukla, Suneet; Zhang, Yun-Kai; Wang, Yi-Jun; Kathawala, Rishil J; Robey, Robert W; Zhang, Li; Yang, Dong-Hua; Talele, Tanaji T; Bates, Susan E; Ambudkar, Suresh V; Xu, Rui-Hua; Chen, Zhe-Sheng

2014-06-30

ABCG2 is a potential biomarker causing multidrug resistance (MDR) in Non-Small Cell Lung Cancer (NSCLC). We conducted this study to investigate whether Icotinib, a small-molecule inhibitor of EGFR tyrosine kinase, could interact with ABCG2 transporter in NSCLC. Our results showed that Icotinib reversed ABCG2-mediated MDR by antagonizing the drug efflux function of ABCG2. Icotinib stimulated the ATPase activity in a concentration-dependent manner and inhibited the photolabeling of ABCG2 with [125I]-Iodoarylazidoprazosin, demonstrating that it interacts at the drug-binding pocket. Homology modeling predicted the binding conformation of Icotinib at Asn629 centroid-based grid of ABCG2. However, Icotinib at reversal concentration did not affect the expression levels of AKT and ABCG2. Furthermore, a combination of Icotinib and topotecan exhibited significant synergistic anticancer activity against NCI-H460/MX20 tumor xenografts. However, the inhibition of transport activity of ABCG2 was insufficient to overcome pemetrexed resistance in NCI-H460/MX20 cells, which was due to the co-upregulated thymidylate synthase (TS) and ABCG2 expression. This is the first report to show that the up-regulation of TS in ABCG2-overexpressing cell line NCI-H460/MX20 may play a role of resistance to pemetrexate. Our findings suggested different possible strategies of overcoming the resistance of topotecan and pemetrexed in the NSCLC patients.

Activation of Liver X Receptor Decreases Atherosclerosis in Ldlr−/− mice in the Absence of ABCA1 and ABCG1 in Myeloid Cells

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Kappus, Mojdeh S.; Murphy, Andrew J.; Abramowicz, Sandra; Ntonga, Vusisizwe; Welch, Carrie L.; Tall, Alan R.; Westerterp, Marit

2014-01-01

Objective Liver X Receptor (LXR) activators decrease atherosclerosis in mice. LXR activators (1) directly up-regulate genes involved in reverse cholesterol transport (RCT) and (2) exert anti-inflammatory effects mediated by transrepression of NFκB target genes. We investigated whether myeloid cell deficiency of ATP-binding cassette transporters A1 and G1 (ABCA1/G1), principal targets of LXR that promote macrophage cholesterol efflux and initiate RCT, would abolish the beneficial effects of LXR activation on atherosclerosis. Approach and Results LXR activator T0901317 (T0) substantially reduced inflammatory gene expression in macrophages lacking ABCA1/G1. Ldlr−/− mice were transplanted with Abca1−/−Abcg1−/− or wild-type bone marrow (BM) and fed a Western-type diet (WTD) for 6 weeks with or without T0 supplementation. Abca1/g1 BM deficiency increased atherosclerotic lesion complexity and inflammatory cell infiltration into the adventitia and myocardium. T0 markedly decreased lesion area, complexity and inflammatory cell infiltration in the Abca1−/−Abcg1−/− BM transplanted mice. To investigate whether this was due to macrophage Abca1/g1 deficiency, Ldlr−/− mice were transplanted with LysmCreAbca1fl/flAbcg1fl/fl or Abca1fl/flAbcg1fl/fl BM and fed WTD with or without the more specific LXR agonist GW3965 for 12 weeks. GW3965 decreased lesion size in both groups and the decrease was more prominent in the LysmCreAbca1fl/flAbcg1fl/fl group. Conclusions The results suggest that anti-inflammatory effects of LXR activators are of key importance to their anti-atherosclerotic effects in vivo independent of cholesterol efflux pathways mediated by macrophage ABCA1/G1. This has implications for the development of LXR activators that lack adverse effects on lipogenic genes while maintaining the ability to trans-repress inflammatory genes. PMID:24311381

Generation of an ABCG2GFPn-puro transgenic line - A tool to study ABCG2 expression in mice

International Nuclear Information System (INIS)

Orford, Michael; Mean, Richard; Lapathitis, George; Genethliou, Nicholas; Panayiotou, Elena; Panayi, Helen; Malas, Stavros

2009-01-01

The ATP-binding cassette (ABC) transporter 2 (ABCG2) is expressed by stem cells in many organs and in stem cells of solid tumors. These cells are isolated based on the side population (SP) phenotype, a Hoechst 3342 dye efflux property believed to be conferred by ABCG2. Because of the limitations of this approach we generated transgenic mice that express Nuclear GFP (GFPn) coupled to the Puromycin-resistance gene, under the control of ABCG2 promoter/enhancer sequences. We show that ABCG2 is expressed in neural progenitors of the developing forebrain and spinal cord and in embryonic and adult endothelial cells of the brain. Using the neurosphere assay, we isolated tripotent ABCG2-expressing neural stem cells from embryonic mouse brain. This transgenic line is a powerful tool for studying the expression of ABCG2 in many tissues and for performing functional studies in different experimental settings.

Cognition, learning behaviour and hippocampal synaptic plasticity are not disrupted in mice over-expressing the cholesterol transporter ABCG1

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Eadie Brennan D

2009-02-01

Full Text Available Abstract Background Cognitive deficits are a hallmark feature of both Down Syndrome (DS and Alzheimer's Disease (AD. Extra copies of the genes on chromosome 21 may also play an important role in the accelerated onset of AD in DS individuals. Growing evidence suggests an important function for cholesterol in the pathogenesis of AD, particularly in APP metabolism and production of Aβ peptides. The ATP-Binding Cassette-G1 (ABCG1 transporter is located on chromosome 21, and participates in the maintenance of tissue cholesterol homeostasis. Results To assess the role of ABCG1 in DS-related cognition, we evaluated the cognitive performance of mice selectively over-expressing the ABCG1 gene from its endogenous regulatory signals. Both wild-type and ABCG1 transgenic mice performed equivalently on several behavioral tests, including measures of anxiety, as well as on reference and working memory tasks. No deficits in hippocampal CA1 synaptic plasticity as determined with electrophysiological studies were apparent in mice over-expressing ABCG1. Conclusion These findings indicate that although ABCG1 may play a role in maintaining cellular or tissue cholesterol homeostasis, it is unlikely that excess ABCG1 expression contributes to the cognitive deficits in DS individuals.

Contrasting roles of the ABCG2 Q141K variant in prostate cancer

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Sobek, Kathryn M. [Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Cummings, Jessica L. [Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Bacich, Dean J. [Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Department of Urology, University of Texas Health Science Center, San Antonio, TX (United States); O’Keefe, Denise S., E-mail: OKeefeD@uthscsa.edu [Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Department of Urology, University of Texas Health Science Center, San Antonio, TX (United States)

2017-05-01

ABCG2 is a membrane transport protein that effluxes growth-promoting molecules, such as folates and dihydrotestosterone, as well as chemotherapeutic agents. Therefore it is important to determine how variants of ABCG2 affect the transporter function in order to determine whether modified treatment regimens may be necessary for patients harboring ABCG2 variants. Previous studies have demonstrated an association between the ABCG2 Q141K variant and overall survival after a prostate cancer diagnosis. We report here that in patients with recurrent prostate cancer, those who carry the ABCG2 Q141K variant had a significantly shorter time to PSA recurrence post-prostatectomy than patients homozygous for wild-type ABCG2 (P=0.01). Transport studies showed that wild-type ABCG2 was able to efflux more folic acid than the Q141K variant (P<0.002), suggesting that retained tumoral folate contributes to the decreased time to PSA recurrence in the Q141K variant patients. In a seemingly conflicting study, it was previously reported that docetaxel-treated Q141K variant prostate cancer patients have a longer survival time. We found this may be due to less efficient docetaxel efflux in cells with the Q141K variant versus wild-type ABCG2. In human prostate cancer tissues, confocal microscopy revealed that all genotypes had a mixture of cytoplasmic and plasma membrane staining, with noticeably less staining in the two homozygous KK patients. In conclusion, the Q141K variant plays contrasting roles in prostate cancer: 1) by decreasing folate efflux, increased intracellular folate levels result in enhanced tumor cell proliferation and therefore time to recurrence decreases; and 2) in patients treated with docetaxel, by decreasing its efflux, intratumoral docetaxel levels and tumor cell drug sensitivity increase and therefore patient survival time increases. Taken together, these data suggest that a patient's ABCG2 genotype may be important when determining a personalized treatment

Association between ABCG1 polymorphism rs1893590 and high-density lipoprotein (HDL) in an asymptomatic Brazilian population.

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Zago, V H S; Scherrer, D Z; Parra, E S; Panzoldo, N B; Alexandre, F; Nakandakare, E R; Quintão, E C R; de Faria, E C

2015-03-01

ATP binding cassette transporter G1 (ABCG1) promotes lipidation of nascent high-density lipoprotein (HDL) particles, acting as an intracellular transporter. SNP rs1893590 (c.-204A > C) of ABCG1 gene has been previously studied and reported as functional over plasma HDL-C and lipoprotein lipase activity. This study aimed to investigate the relationships of SNP rs1893590 with plasma lipids and lipoproteins in a large Brazilian population. Were selected 654 asymptomatic and normolipidemic volunteers from both genders. Clinical and anthropometrical data were taken and blood samples were drawn after 12 h fasting. Plasma lipids and lipoproteins, as well as HDL particle size and volume were determined. Genomic DNA was isolated for SNP rs1893590 detection by TaqMan(®) OpenArray(®) Real-Time PCR Plataform (Applied Biosystems). Mann-Whitney U, Chi square and two-way ANOVA were the used statistical tests. No significant differences were found in the comparison analyses between the allele groups for all studied parameters. Conversely, significant interactions were observed between SNP and age over plasma HDL-C, were volunteers under 60 years with AA genotype had increased HDL-C (p = 0.048). Similar results were observed in the group with body mass index (BMI) m(2), where volunteers with AA genotype had higher HDL-C levels (p = 0.0034), plus an increased HDL particle size (p = 0.01). These findings indicate that SNP rs1893590 of ABCG1 has a significant impact over HDL-C under asymptomatic clinical conditions in an age and BMI dependent way.

CORRELATION BETWEEN CHEMOTHERAPY RESPONSE AND EXPRESSION PROFILES OF TRANSMEMBRANE PROTEINS: P-GLYCOPROTEIN (ABCB1, MRP2 (ABCC2, BCRP (ABCG2 IN PATIENTS WITH INVASIVE BREAST CANCER

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К. Yu. Khristenko

2016-01-01

Full Text Available Overexpression of ABC drug transporters can cause multidrug resistance (MDR in cancer cells, which is a major obstacle in the success of cancer chemotherapy. Our study revealed a correlation between the expression of invasive breast cancer resistance-associated proteins, such as P-glycoprotein (ABCB1, MRP2 (ABCC2, BCRP (ABCG2 in tumor cells and pathologic response to neoadjuvant chemotherapy. The response to neoadjuvant chemotherapy was shown to be associated with a lack of BCRP expression in tumor cells. The pathologic tumor response was correlated with the presence of positive MRP2 expression and the expression level of P-glycoprotein in cells of invasive breast cancer. 

Generation of an ABCG2{sup GFPn-puro} transgenic line - A tool to study ABCG2 expression in mice

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Orford, Michael; Mean, Richard; Lapathitis, George; Genethliou, Nicholas; Panayiotou, Elena; Panayi, Helen [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios 2370, Nicosia (Cyprus); Malas, Stavros, E-mail: smalas@cing.ac.cy [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios 2370, Nicosia (Cyprus); Department of Biological Sciences, University of Cyprus, P.O. Box 20537, 1678 Nicosia (Cyprus)

2009-06-26

The ATP-binding cassette (ABC) transporter 2 (ABCG2) is expressed by stem cells in many organs and in stem cells of solid tumors. These cells are isolated based on the side population (SP) phenotype, a Hoechst 3342 dye efflux property believed to be conferred by ABCG2. Because of the limitations of this approach we generated transgenic mice that express Nuclear GFP (GFPn) coupled to the Puromycin-resistance gene, under the control of ABCG2 promoter/enhancer sequences. We show that ABCG2 is expressed in neural progenitors of the developing forebrain and spinal cord and in embryonic and adult endothelial cells of the brain. Using the neurosphere assay, we isolated tripotent ABCG2-expressing neural stem cells from embryonic mouse brain. This transgenic line is a powerful tool for studying the expression of ABCG2 in many tissues and for performing functional studies in different experimental settings.

The Human ABCG1 Transporter Mobilizes Plasma Membrane and Late Endosomal Non-Sphingomyelin-Associated-Cholesterol for Efflux and Esterification

Directory of Open Access Journals (Sweden)

Edward B. Neufeld

2014-12-01

Full Text Available We have previously shown that GFP-tagged human ABCG1 on the plasma membrane (PM and in late endosomes (LE mobilizes sterol on both sides of the membrane lipid bilayer, thereby increasing cellular cholesterol efflux to lipid surfaces. In the present study, we examined ABCG1-induced changes in membrane cholesterol distribution, organization, and mobility. ABCG1-GFP expression increased the amount of mobile, non-sphingomyelin(SM-associated cholesterol at the PM and LE, but not the amount of SM-associated-cholesterol or SM. ABCG1-mobilized non-SM-associated-cholesterol rapidly cycled between the PM and LE and effluxed from the PM to extracellular acceptors, or, relocated to intracellular sites of esterification. ABCG1 increased detergent-soluble pools of PM and LE cholesterol, generated detergent-resistant, non-SM-associated PM cholesterol, and increased resistance to both amphotericin B-induced (cholesterol-mediated and lysenin-induced (SM-mediated cytolysis, consistent with altered organization of both PM cholesterol and SM. ABCG1 itself resided in detergent-soluble membrane domains. We propose that PM and LE ABCG1 residing at the phase boundary between ordered (Lo and disordered (Ld membrane lipid domains alters SM and cholesterol organization thereby increasing cholesterol flux between Lo and Ld, and hence, the amount of cholesterol available for removal by acceptors on either side of the membrane bilayer for either efflux or esterification.

Expression and Significance of Stem Cell Markers CK19, Notch3, CD133, P75NTR, STRO-1 and ABCG2 in Pulmonary Squamous Carcinomas

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Xuyong LIN, , , , ,

2009-04-01

Full Text Available Background and objective Increasing reports showed that some tumor stem cells were selfrenewal and multi-lineage differentiated in tumors, similar to the normal stem cells in human body. The aim of this study is to observe the expression of stem cell markers in lung squamous carcinoma tissues. Methods Fifty-four lung cancer specimens from surgery were analyzed for CK19, Notch3, CD133, P75NTR, STRO-1 and ABCG2 expression by using S-P immunohistochemistry. In addition, ten normal lung tissue samples were included as control. Results CK19, Notch3, CD133 and ABCG2 were expressed in 54 Lung cancer tissues, without expression of P75NTR and STRO-1. The expressionrate of CK19, Notch3, CD133 and ABCG2 was 66.67% (36/54, 87.04% (47/54, 50% (27/54, and 61.11% (33/54 respectively. The levels of expression of Notch3, CD133 and ABCG2 were significantly lower in high differentiation group than those in moderate and low differentiation group (P <0.05. The levels of expression of CK19, CD133 and ABCG2 were significantly higher in lymph node metastasis group than those in non-metastasis group (P <0.05. The percentage of total positive cells of four stem cell markers in serial tissue sections was lower than 2%. Conclusion There was expression ofsome stem cell markers in pulmonary squamous carcinomas, and there was relationship between expression degree withdifferentiation degree and lymph node metastasis.

A preliminary study of the relationship between promoter methylation of the ABCG1, GALNT2 and HMGCR genes and coronary heart disease.

Directory of Open Access Journals (Sweden)

Ping Peng

Full Text Available To investigate the association of ABCG1, GALNT2 and HMGCR genes promoter DNA methylation with coronary heart disease (CHD and explore the interaction between their methylation status and the CHD patients' clinical characteristics in Han Chinese population.Methylation-specific polymerase chain reaction (MSP technology was used to examine the role of the aberrant gene promoter methylation in CHD in Han Chinese population. A total of 85 CHD patients and 54 participants without CHD confirmed by angiography were recruited. 82.8% of the participants with ABCG1 gene promoter hypermethylation have CHD, while only 17.4% of the participants without hypermethylation have it. The average age of the participants with GALNT2 gene promoter hypermethylation is 62.10 ± 8.21, while that of the participants without hypermethylation is 57.28 ± 9.87; in the former group, 75.4% of the participants have CHD, compared to only 50% in the latter group. As for the HMGCR gene, the average age of the participants with promoter hypermethylation is 63.24 ± 8.10 and that of the participants without hypermethylation is 57.79 ± 9.55; its promoter hypermethylation is likely to be related to smoking. Our results indicated a significant statistical association of promoter methylation of the ABCG1 gene with increased risk of CHD (OR = 19.966; 95% CI, 7.319-54.468; P*<0.001; P*: adjusted for age, gender, smoking, lipid level, hypertension, and diabetes. Similar results were obtained for that of the GALNT2 gene (OR = 2.978; 95% CI, 1.335-6.646; P* = 0.008, but not of HMGCR gene (OR = 1.388; 95% CI, 0.572-3.371; P*  = 0.469.The present work provides evidence to support the association of promoter DNA methylation status with the risk profile of CHD. Our data indicates that promoter DNA hypermethylation of the ABCG1 and GALNT2 genes, but not the HMGCR gene, is associated with an increased risk of CHD. CHD, smoking and aging are likely to be the important factors influencing DNA

Degradation of AF1Q by chaperone-mediated autophagy

International Nuclear Information System (INIS)

Li, Peng; Ji, Min; Lu, Fei; Zhang, Jingru; Li, Huanjie; Cui, Taixing; Li Wang, Xing; Tang, Dongqi; Ji, Chunyan

2014-01-01

AF1Q, a mixed lineage leukemia gene fusion partner, is identified as a poor prognostic biomarker for pediatric acute myeloid leukemia (AML), adult AML with normal cytogenetic and adult myelodysplastic syndrome. AF1Q is highly regulated during hematopoietic progenitor differentiation and development but its regulatory mechanism has not been defined clearly. In the present study, we used pharmacological and genetic approaches to influence chaperone-mediated autophagy (CMA) and explored the degradation mechanism of AF1Q. Pharmacological inhibitors of lysosomal degradation, such as chloroquine, increased AF1Q levels, whereas activators of CMA, including 6-aminonicotinamide and nutrient starvation, decreased AF1Q levels. AF1Q interacts with HSPA8 and LAMP-2A, which are core components of the CMA machinery. Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. Using an amino acid deletion AF1Q mutation plasmid, we identified that AF1Q had a KFERQ-like motif which was recognized by HSPA8 for CMA-dependent proteolysis. In conclusion, we demonstrate for the first time that AF1Q can be degraded in lysosomes by CMA. - Highlights: • Chaperone-mediated autophagy (CMA) is involved in the degradation of AF1Q. • Macroautophagy does not contribute to the AF1Q degradation. • AF1Q has a KFERQ-like motif that is recognized by CMA core components

Degradation of AF1Q by chaperone-mediated autophagy

Energy Technology Data Exchange (ETDEWEB)

Li, Peng; Ji, Min; Lu, Fei; Zhang, Jingru [Department of Hematology, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan 250012 (China); Li, Huanjie; Cui, Taixing; Li Wang, Xing [Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan 250012 (China); Tang, Dongqi, E-mail: tangdq@sdu.edu.cn [Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan 250012 (China); Center for Stem Cell and Regenerative Medicine, The Second Hospital of Shandong University, Jinan 250033 (China); Ji, Chunyan, E-mail: jichunyan@sdu.edu.cn [Department of Hematology, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan 250012 (China)

2014-09-10

AF1Q, a mixed lineage leukemia gene fusion partner, is identified as a poor prognostic biomarker for pediatric acute myeloid leukemia (AML), adult AML with normal cytogenetic and adult myelodysplastic syndrome. AF1Q is highly regulated during hematopoietic progenitor differentiation and development but its regulatory mechanism has not been defined clearly. In the present study, we used pharmacological and genetic approaches to influence chaperone-mediated autophagy (CMA) and explored the degradation mechanism of AF1Q. Pharmacological inhibitors of lysosomal degradation, such as chloroquine, increased AF1Q levels, whereas activators of CMA, including 6-aminonicotinamide and nutrient starvation, decreased AF1Q levels. AF1Q interacts with HSPA8 and LAMP-2A, which are core components of the CMA machinery. Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. Using an amino acid deletion AF1Q mutation plasmid, we identified that AF1Q had a KFERQ-like motif which was recognized by HSPA8 for CMA-dependent proteolysis. In conclusion, we demonstrate for the first time that AF1Q can be degraded in lysosomes by CMA. - Highlights: • Chaperone-mediated autophagy (CMA) is involved in the degradation of AF1Q. • Macroautophagy does not contribute to the AF1Q degradation. • AF1Q has a KFERQ-like motif that is recognized by CMA core components.

Population-specific association between ABCG2 variants and tophaceous disease in people with gout.

Science.gov (United States)

He, Wendy; Phipps-Green, Amanda; Stamp, Lisa K; Merriman, Tony R; Dalbeth, Nicola

2017-03-07

Tophi contribute to musculoskeletal disability, joint damage and poor health-related quality of life in people with gout. The aim of this study was to examine the role of SLC2A9 and ABCG2 variants in tophaceous disease in people with gout. Participants (n = 1778) with gout fulfilling the 1977 American Rheumatism Association (ARA) classification criteria, who were recruited from primary and secondary care, attended a detailed study visit. The presence of palpable tophi was recorded. SLC2A9 rs11942223, ABCG2 rs2231142 and ABCG2 rs10011796 were genotyped. Data were analysed according to tophus status. Compared to participants without tophi, those with tophi were older, had longer disease duration and higher serum creatinine, and were more likely to be of Māori or Pacific (Polynesian) ancestry. SLC2A9 rs11942223 was not associated with tophi. However, the risk alleles for both ABCG2 single nucleotide polymorphisms (SNPs) were present more frequently in those with tophi (OR (95% CI) 1.24 (1.02-1.51) for rs2231142 and 1.33 (1.01-1.74) for rs10011796, p gout.

ABCG2-mediated suppression of chlorin e6 accumulation and photodynamic therapy efficiency in glioblastoma cell lines can be reversed by KO143.

Science.gov (United States)

Abdel Gaber, Sara A; Müller, Patricia; Zimmermann, Wolfgang; Hüttenberger, Dirk; Wittig, Rainer; Abdel Kader, Mahmoud H; Stepp, Herbert

2018-01-01

Photodynamic therapy (PDT) of malignant brain tumors is a promising adjunct to standard treatment, especially if tumor stem cells thought to be responsible for tumor progression and therapy resistance were also susceptible to this kind of treatment. However, some photosensitizers have been reported to be substrates of ABCG2, one of the membrane transporters mediating resistance to chemotherapy. Here we investigate, whether inhibition of ABCG2 can restore sensitivity to photosensitizer chlorin e6-mediated PDT. Accumulation of chlorin e6 in wild type U87 and doxycycline-inducible U251 glioblastoma cells with or without induction of ABCG2 expression or ABCG2 inhibition by KO143 was analyzed using flow cytometry. In U251 cells, ABCG2 was inducible by doxycycline after stable transfection with a tet-on expression plasmid. Tumor sphere cultivation under low attachment conditions was used to enrich for cells with stem cell-like properties. PDT was done on monolayer cell cultures by irradiation with laser light at 665nm. Elevated levels of ABCG2 in U87 cells grown as tumor spheres or in U251 cells after ABCG2 induction led to a 6-fold lower accumulation of chlorin e6 and the light dose needed to reduce cell viability by 50% (LD50) was 2.5 to 4-fold higher. Both accumulation and PDT response can be restored by KO143, an efficient non-toxic inhibitor of ABCG2. Glioblastoma stem cells might escape phototoxic destruction by ABCG2-mediated reduction of photosensitizer accumulation. Inhibition of ABCG2 during photosensitizer accumulation and irradiation promises to restore full susceptibility of this crucial tumor cell population to photodynamic treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of residues in ABCG2 affecting protein trafficking and drug transport, using co-evolutionary analysis of ABCG sequences.

Science.gov (United States)

Haider, Ameena J; Cox, Megan H; Jones, Natalie; Goode, Alice J; Bridge, Katherine S; Wong, Kelvin; Briggs, Deborah; Kerr, Ian D

2015-07-17

ABCG2 is an ABC (ATP-binding cassette) transporter with a physiological role in urate transport in the kidney and is also implicated in multi-drug efflux from a number of organs in the body. The trafficking of the protein and the mechanism by which it recognizes and transports diverse drugs are important areas of research. In the current study, we have made a series of single amino acid mutations in ABCG2 on the basis of sequence analysis. Mutant isoforms were characterized for cell surface expression and function. One mutant (I573A) showed disrupted glycosylation and reduced trafficking kinetics. In contrast with many ABC transporter folding mutations which appear to be 'rescued' by chemical chaperones or low temperature incubation, the I573A mutation was not enriched at the cell surface by either treatment, with the majority of the protein being retained in the endoplasmic reticulum (ER). Two other mutations (P485A and M549A) showed distinct effects on transport of ABCG2 substrates reinforcing the role of TM helix 3 in drug recognition and transport and indicating the presence of intracellular coupling regions in ABCG2. © 2015 Authors.

Development of imatinib and dasatinib resistance: dynamics of expression of drug transporters ABCB1, ABCC1, ABCG2, MVP, and SLC22A1.

Science.gov (United States)

Gromicho, Marta; Dinis, Joana; Magalhães, Marta; Fernandes, Alexandra R; Tavares, Purificação; Laires, António; Rueff, José; Rodrigues, António Sebastião

2011-10-01

About 20% of patients with chronic myeloid leukemia (CML) do not respond to treatment with imatinib either initially or because of acquired resistance. To study the development of CML drug resistance, an in vitro experimental system comprising cell lines with different resistance levels was established by exposing K562 cells to increasing concentrations of imatinib and dasatinib anticancer agents. The mRNA levels of BCR- ABL1 and of genes involved in drug transport or redistribution (ABCB1, ABCC1, ABCC3, ABCG2, MVP, and SLC22A1) were measured and the ABL1 kinase domain sequenced. Results excluded BCR- ABL1 overexpression and mutations as relevant resistance mechanisms. Most studied transporters were overexpressed in the majority of resistant cell lines. Their expression pattern was dynamic: varying with resistance level and chronic drug exposure. Studied efflux transporters may have an important role at the initial stages of resistance, but after prolonged exposure and for higher doses of drugs other mechanisms might take place.

Implications of ABCG2 Expression on Irinotecan Treatment of Colorectal Cancer Patients

DEFF Research Database (Denmark)

Nielsen, Dorte Lisbet; Palshof, Jesper Andreas; Bruenner, Nils

2017-01-01

Background: One of the main chemotherapeutic drugs used on a routine basis in patients with metastatic colorectal cancer ((m)CRC) is the topoisomerase-1 inhibitor, irinotecan. However, its usefulness is limited by the pre-existing or inevitable development of resistance. The ATP-binding cassette...... to irinotecan treatment in CRC patients. Results: Few studies have evaluated the association between ABCG2 gene or protein expression and prognosis in CRC patients. Discordant results were reported. The discrepancies might be explained by the use of different criteria for interpretation of results...... (ABC) transporter ABCG2/breast cancer resistance protein (BRCP) through its function in xenobiotic clearance might play an important role in irinotecan resistance. With a goal to evaluate the clinical significance of ABCG2 measurements, we here review the current literature on ABCG2 in relation...

Dicty_cDB: Contig-U03802-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available T-2KB Trichosurus... 48 3e-11 4 ( DY894715 ) CeleSEQ14351 Cunninghamella elegans pBluescript (... 58 4e-11 3... letters Score E Sequences producing significant alignments: (bits) Value Contig-U03802-1 (Contig-U... letters Searching..................................................done Score E Sequences producing significant al...1... 62 4e-05 1 ( EJ306703 ) 1095390099376 Global-Ocean-Sampling_GS-27-01-01-1... 62 4e-05 1 ( CP000238 ) Baumannia cicadellinicola... AY241394 |pid:none) Melopsittacus undulatus Mn superox... 244 2e-63 AF329270_1( AF329270 |pid:none) Gallus gallus manganes

Vector coherent state representations of SO5 contains SU2 + SU2 contains U1 + U1 and SO5 contains U1 + U1

International Nuclear Information System (INIS)

Pan Feng

1991-01-01

VCS representations of SO 5 contains SU 2 + SU 2 contains U 1 + U 1 and SO 5 contains U 1 + U 1 are discussed. Reduced matrix elements for SO 5 contains SU 2 + SU 2 are derived. The multiplicity of a weight for SO 5 is determined by using the K-matrix technique

Constitutive androstane receptor upregulates Abcb1 and Abcg2 at the blood-brain barrier after CITCO activation.

Science.gov (United States)

Lemmen, Julia; Tozakidis, Iasson E P; Bele, Prachee; Galla, Hans-Joachim

2013-03-21

ATP-driven efflux transporters are considered to be the major hurdle in the treatment of central nervous system (CNS) diseases. Abcb1 (P-glycoprotein) and Abcg2 (breast cancer resistance protein/brain multidrug resistance protein) belong to the best known ABC-transporters. These ABC-transporters limit the permeability of the blood-brain barrier and protect the brain against toxic compounds in the blood but on the other hand they also reduce the efficacy of CNS pharmacotherapy. Even after 40 years of extensive research, the regulatory mechanisms of these efflux transporters are still not completely understood. To unravel the efflux transporter regulation, we analyzed the effect of the nuclear receptor CAR (constitutive androstane receptor) on the expression of Abcb1 and Abcg2 in primary cultures of porcine brain capillary endothelial cells (PBCEC). CAR is a xenobiotic-activated transcription factor, which is, like the other important nuclear receptor pregnane X receptor (PXR), highly expressed in barrier tissue and known to be a positive regulator of ABC-transporters. We demonstrate that activation of porcine CAR by the human CAR (hCAR) ligand CITCO (6-(4-chlorophenyl)-imidazo[2,1-b]thiazole-5-carbaldehyde) leads to an up-regulation of both transporters, whereas the mouse-specific CAR ligand TCPOBOP (1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene) had no effect on transporter expression. The stimulation of PBCEC with CITCO caused a significant up-regulation of both efflux-transporters on RNA-level, protein level and transport level. Furthermore the additional application of a CAR inhibitor significantly decreased the transporter expression to control niveau. In conclusion our data prove CAR activation only by the human ligand CITCO leading to an increased ABC-transporter expression and transport activity. Copyright © 2013 Elsevier B.V. All rights reserved.

Lack of ABCG2 shortens latency of BRCA1-deficient mammary tumors and this is not affected by genistein or resveratrol

NARCIS (Netherlands)

Zander, Serge A. L.; Kersbergen, Ariena; Sol, Wendy; Gonggrijp, Maaike; van de Wetering, Koen; Jonkers, Jos; Borst, Piet; Rottenberg, Sven

2012-01-01

In addition to their role in drug resistance, the ATP-binding cassette (ABC) transporters ABCG2 and ABCB1 have been suggested to protect cells from a broad range of substances that may foster tumorigenesis. Phytoestrogens or their metabolites are substrates of these transporters and the influence of

Lack of biliary lipid excretion in the little skate, Raja erinacea, indicates the absence of functional Mdr2, Abcg5, and Abcg8 transporters

NARCIS (Netherlands)

Elferink, Ronald P. J. Oude; Ottenhoff, Roelof; Fricker, Gert; Seward, David J.; Ballatori, Nazzareno; Boyer, James

2004-01-01

The ABC transporters bile salt export pump ( BSEP; encoded by the ABCB11 gene), MDR3 P-glycoprotein (ABCB4), and sterolin 1 and 2 (ABCG5 and ABCG8) are crucial for the excretion of bile salt, phospholipid, and cholesterol, respectively, into the bile of mammals. The current paradigm is that

Functional non-synonymous variants of ABCG2 and gout risk.

Science.gov (United States)

Stiburkova, Blanka; Pavelcova, Katerina; Zavada, Jakub; Petru, Lenka; Simek, Pavel; Cepek, Pavel; Pavlikova, Marketa; Matsuo, Hirotaka; Merriman, Tony R; Pavelka, Karel

2017-11-01

Common dysfunctional variants of ATP binding cassette subfamily G member 2 (Junior blood group) (ABCG2), a high-capacity urate transporter gene, that result in decreased urate excretion are major causes of hyperuricemia and gout. In the present study, our objective was to determine the frequency and effect on gout of common and rare non-synonymous and other functional allelic variants in the ABCG2 gene. The main cohort recruited from the Czech Republic consisted of 145 gout patients; 115 normouricaemic controls were used for comparison. We amplified, directly sequenced and analysed 15 ABCG2 exons. The associations between genetic variants and clinical phenotype were analysed using the t-test, Fisher's exact test and a logistic and linear regression approach. Data from a New Zealand Polynesian sample set and the UK Biobank were included for the p.V12M analysis. In the ABCG2 gene, 18 intronic (one dysfunctional splicing) and 11 exonic variants were detected: 9 were non-synonymous (2 common, 7 rare including 1 novel), namely p.V12M, p.Q141K, p.R147W, p.T153M, p.F373C, p.T434M, p.S476P, p.D620N and p.K360del. The p.Q141K (rs2231142) variant had a significantly higher minor allele frequency (0.23) in the gout patients compared with the European-origin population (0.09) and was significantly more common among gout patients than among normouricaemic controls (odds ratio = 3.26, P gout (42 vs 48 years, P = 0.0143) and a greater likelihood of a familial history of gout (41% vs 27%, odds ratio = 1.96, P = 0.053). In a meta-analysis p.V12M exerted a protective effect from gout (P gout. Non-synonymous allelic variants of ABCG2 had a significant effect on earlier onset of gout and the presence of a familial gout history. ABCG2 should thus be considered a common and significant risk factor for gout. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Dicty_cDB: Contig-U11323-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available AF134321 |pid:none) Dissostichus mawsoni clone Dm7m ch... 84 3e-14 AM747721_702( ...S101... 81 2e-13 U58944_1( U58944 |pid:none) Dissostichus mawsoni AFGP antifreeze g... 81 2e-13 AM182501_1( ...017194_2467( AE017194 |pid:none) Bacillus cereus ATCC 10987, com... 75 1e-11 U43149_1( U43149 |pid:none) Dissostichus mawson

Rice Stomatal Closure Requires Guard Cell Plasma Membrane ATP-Binding Cassette Transporter RCN1/OsABCG5.

Science.gov (United States)

Matsuda, Shuichi; Takano, Sho; Sato, Moeko; Furukawa, Kaoru; Nagasawa, Hidetaka; Yoshikawa, Shoko; Kasuga, Jun; Tokuji, Yoshihiko; Yazaki, Kazufumi; Nakazono, Mikio; Takamure, Itsuro; Kato, Kiyoaki

2016-03-07

Water stress is one of the major environmental stresses that affect agricultural production worldwide. Water loss from plants occurs primarily through stomatal pores. Here, we report that an Oryza sativa half-size ATP-binding cassette (ABC) subfamily G protein, RCN1/OsABCG5, is involved in stomatal closure mediated by phytohormone abscisic acid (ABA) accumulation in guard cells. We found that the GFP-RCN1/OsABCG5-fusion protein was localized at the plasma membrane in guard cells. The percentage of guard cell pairs containing both ABA and GFP-RCN1/OsABCG5 increased after exogenous ABA treatment, whereas they were co-localized in guard cell pairs regardless of whether exogenous ABA was applied. ABA application resulted in a smaller increase in the percentage of guard cell pairs containing ABA in rcn1 mutant (A684P) and RCN1-RNAi than in wild-type plants. Furthermore, polyethylene glycol (drought stress)-inducible ABA accumulation in guard cells did not occur in rcn1 mutants. Stomata closure mediated by exogenous ABA application was strongly reduced in rcn1 mutants. Finally, rcn1 mutant plants had more rapid water loss from detached leaves than the wild-type plants. These results indicate that in response to drought stress, RCN1/OsABCG5 is involved in accumulation of ABA in guard cells, which is indispensable for stomatal closure. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

The multidrug transporter ABCG2 (BCRP) is inhibited by plant-derived cannabinoids.

Science.gov (United States)

Holland, M L; Lau, D T T; Allen, J D; Arnold, J C

2007-11-01

Cannabinoids are used therapeutically for the palliation of the adverse side effects associated with cancer chemotherapy. However, cannabinoids also inhibit both the activity and expression of the multidrug transporter, P-glycoprotein in vitro. Here we address the interaction of cannabinol (CBN), cannabidiol (CBD) and delta 9-tetrahydrocannabinol (THC) with the related multidrug transporter, ABCG2. Cannabinoid inhibition of Abcg2/ABCG2 was assessed using flow cytometric analysis of substrate accumulation and ATPase activity assays. The cytotoxicity and chemosensitization by cannabinoids was determined with cell viability assays. Expression of cannabinoid and vanilloid receptors was assessed using reverse transcriptase polymerase chain reaction, and cannabinoid modulation of ABCG2 expression was examined using immunoblotting. CBN, CBD and THC increased the intracellular accumulation of the Abcg2/ABCG2 substrate, mitoxantrone, in an over-expressing cell line. The THC metabolite, (-)-11-nor-9-carboxy-delta 9-THC was much less potent. The plant cannabinoids inhibited both basal and substrate stimulated ATPase activity of human ABCG2. Cannabinoid cytotoxicity occurred in the absence of known cannabinoid cell surface receptors, and only at concentrations higher than those required for Abcg2/ABCG2 inhibition. Sub-toxic concentrations of the cannabinoids resensitized the overexpressing cell line to the cytotoxic effect of Abcg2/ABCG2 substrates, mitoxantrone and topotecan. This occurred in the absence of any effect on ABCG2 expression. Cannabinoids are novel Abcg2/ABCG2 inhibitors, reversing the Abcg2-mediated multidrug-resistant phenotype in vitro. This finding may have implications for the co-administration of cannabinoids with pharmaceuticals that are ABCG2 substrates.

Breast cancer resistance protein (Bcrp1/Abcg2) limits net intestinal uptake of quercetin in rats by facilitating apical efflux of glucuronides

NARCIS (Netherlands)

Sesink, A.L.A.; Arts, I.C.W.; Boer, de V.C.J.; Breedveld, P.; Schellens, J.H.M.; Hollman, P.C.H.; Russel, F.G.M.

2005-01-01

The intestinal absorption of the flavonoid quercetin in rats is limited by the secretion of glucuronidated metabolites back into the gut lumen. The objective of this study was to determine the role of the intestinal efflux transporters breast cancer resistance protein (Bcrp1)/Abcg2 and multidrug

Breast cancer resistance protein (Bcrp1/Abcg2) limits net intestinal uptake of quercetin in rats by facilitating apical efflux of glucuronides.

NARCIS (Netherlands)

Sesink, A.L.; Arts, I.C.; Boer, V.C. de; Breedveld, P.; Schellens, J.H.; Hollman, P.C.H.; Russel, F.G.M.

2005-01-01

The intestinal absorption of the flavonoid quercetin in rats is limited by the secretion of glucuronidated metabolites back into the gut lumen. The objective of this study was to determine the role of the intestinal efflux transporters breast cancer resistance protein (Bcrp1)/Abcg2 and multidrug

Deficiency of ABCA1 and ABCG1 in Macrophages Increases Inflammation and Accelerates Atherosclerosis in Mice

Science.gov (United States)

Westerterp, Marit; Murphy, Andrew J.; Wang, Mi; Pagler, Tamara A.; Vengrenyuk, Yuliya; Kappus, Mojdeh S.; Gorman, Darren J.; Nagareddy, Prabhakara R.; Zhu, Xuewei; Abramowicz, Sandra; Parks, John S.; Welch, Carrie; Fisher, Edward A.; Wang, Nan; Yvan-Charvet, Laurent; Tall, Alan R.

2013-01-01

Rationale Plasma HDL levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is due to the ability of HDL to promote cholesterol efflux from macrophage foam cells, direct experimental support for this hypothesis is lacking. Objective To assess the role of macrophage cholesterol efflux pathways in atherogenesis. Methods and Results We developed MAC-ABCDKO mice with efficient deletion of the ATP Binding Cassette Transporters A1 and G1 (ABCA1 and ABCG1) in macrophages but not in hematopoietic stem or progenitor populations. MAC-ABCDKO bone marrow (BM) was transplanted into Ldlr-/- recipients. On the chow diet, these mice had similar plasma cholesterol and blood monocyte levels but increased atherosclerosis compared to controls. On the Western type diet (WTD), MAC-ABCDKO BM transplanted Ldlr-/- mice had disproportionate atherosclerosis, considering they also had lower VLDL/LDL cholesterol levels than controls. ABCA1/G1 deficient macrophages in lesions showed increased inflammatory gene expression. Unexpectedly, WTD-fed MAC-ABCDKO BM transplanted Ldlr-/- mice displayed monocytosis and neutrophilia in the absence of HSPC proliferation. Mechanistic studies revealed increased expression of M-CSF and G-CSF in splenic macrophage foam cells, driving BM monocyte and neutrophil production. Conclusion These studies 1) show that macrophage deficiency of ABCA1/G1 is pro-atherogenic likely by promoting plaque inflammation and 2) uncover a novel positive feedback loop in which cholesterol-laden splenic macrophages signal BM progenitors to produce monocytes, with suppression by macrophage cholesterol efflux pathways. PMID:23572498

Crystallization and preliminary X-ray analysis of a U2AF65 variant in complex with a polypyrimidine-tract analogue by use of protein engineering

International Nuclear Information System (INIS)

Sickmier, E. Allen; Frato, Katherine E.; Kielkopf, Clara L.

2006-01-01

A complex of the essential splicing factor U2AF 65 and a deoxyuridine oligonucleotide has been crystallized by modification of an interdomain linker. The large subunit of the essential pre-mRNA splicing factor U2 auxiliary factor (U2AF 65 ) binds the polypyrimidine tract near the 3′ splice site of pre-mRNA introns and directs the association of the U2 small nuclear ribonucleoprotein particle (U2 snRNP) of the spliceosome with the pre-mRNA. Protein engineering, in which the flexible linker region connecting tandem RNA-recognition motifs (RRMs) within the U2AF 65 RNA-binding domain was partially deleted, allowed successful crystallization of the protein–nucleic acid complex. Cocrystals of a U2AF 65 variant with a deoxyuridine dodecamer diffract X-rays to 2.9 Å resolution and contain one complex per asymmetric unit

Cloning and characterization of two duplicated interleukin-17A/F2 genes in common carp (Cyprinus carpio L.): Transcripts expression and bioactivity of recombinant IL-17A/F2.

Science.gov (United States)

Li, Hongxia; Yu, Juhua; Li, Jianlin; Tang, Yongkai; Yu, Fan; Zhou, Jie; Yu, Wenjuan

2016-04-01

Interleukin-17 (IL-17) plays an important role in inflammation and host defense in mammals. In this study, we identified two duplicated IL-17A/F2 genes in the common carp (Cyprinus carpio) (ccIL-17A/F2a and ccIL-17A/F2b), putative encoded proteins contain 140 amino acids (aa) with conserved IL-17 family motifs. Expression analysis revealed high constitutive expression of ccIL-17A/F2s in mucosal tissues, including gill, skin and intestine, their expression could be induced by Aeromonas hydrophila, suggesting a potential role in mucosal immunity. Recombinant ccIL-17A/F2a protein (rccIL-17A/F2a) produced in Escherichia coli could induce the expression of proinflammatory cytokines (IL-1β) and the antimicrobial peptides S100A1, S100A10a and S100A10b in the primary kidney in a dose- and time-dependent manner. Above findings suggest that ccIL-17A/F2 plays an important role in both proinflammatory and innate immunity. Two duplicated ccIL-17A/F2s showed different expression level with ccIL-17A/F2a higher than b, comparison of two 5' regulatory regions indicated the length from anticipated promoter to transcriptional start site (TSS) and putative transcription factor binding site (TFBS) were different. Promoter activity of ccIL-17A/F2a was 2.5 times of ccIL-17A/F2b which consistent with expression results of two genes. These suggest mutations in 5'regulatory region contributed to the differentiation of duplicated genes. To our knowledge, this is the first report to analyze 5'regulatory region of piscine IL-17 family genes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Role of Abcg2 During Mouse Embroyonic Stem Cell Diffferentiation

Science.gov (United States)

Role of Abcg2 During Mouse Embryonic Stem Cell Differentiation. Abcg2 is a multidrug resistance ATP-binding cassette (ABC) transporter whose activity may be considered a hallmark of stem cell plasticity. The role of Abcg2 during early embryogenesis, however, is unclear. Studies...

Genome-Wide Identification and Expression Profiling of ATP-Binding Cassette (ABC) Transporter Gene Family in Pineapple (Ananas comosus (L.) Merr.) Reveal the Role of AcABCG38 in Pollen Development.

Science.gov (United States)

Chen, Piaojuan; Li, Yi; Zhao, Lihua; Hou, Zhimin; Yan, Maokai; Hu, Bingyan; Liu, Yanhui; Azam, Syed Muhammad; Zhang, Ziyan; Rahman, Zia Ur; Liu, Liping; Qin, Yuan

2017-01-01

Pineapple ( Ananas comosus L .) cultivation commonly relies on asexual reproduction which is easily impeded by many factors in agriculture production. Sexual reproduction might be a novel approach to improve the pineapple planting. However, genes controlling pineapple sexual reproduction are still remain elusive. In different organisms a conserved superfamily proteins known as ATP binding cassette (ABC) participate in various biological processes. Whereas, till today the ABC gene family has not been identified in pineapple. Here 100 ABC genes were identified in the pineapple genome and grouped into eight subfamilies (5 ABCAs , 20 ABCB s, 16 ABCCs , 2 ABCDs , one ABCEs , 5 ABCFs , 42 ABCGs and 9 ABCIs ). Gene expression profiling revealed the dynamic expression pattern of ABC gene family in various tissues and different developmental stages. AcABCA5, AcABCB6, AcABCC4 , AcABCC7 , AcABCC9 , AcABCG26 , AcABCG38 and AcABCG42 exhibited preferential expression in ovule and stamen. Over-expression of AcABCG38 in the Arabidopsis double mutant abcg1-2abcg16-2 partially restored its pollen abortion defects, indicating that AcABCG38 plays important roles in pollen development. Our study on ABC gene family in pineapple provides useful information for developing sexual pineapple plantation which could be utilized to improve pineapple agricultural production.

Localization of tritiated 1-(2, 4-dichlorobenzyl)-1H-indazole-3-carboxylic acid ([3H] AF 1890) in rat testis using freeze-drying autoradiography

International Nuclear Information System (INIS)

Hilderbrandt-Stark, H.E.; Mills, J.W.; Fawcett, D.W.

1982-01-01

Tritiated 1-(2, 4-dichlorobenzyl)- 1 H-indazole-3-carboxylic acid ([ 3 H]AF 1890) was localized within rat testis using freeze-drying autoradiographic techniques. Ligated seminiferous tubule preparations were exposed in vitro to 80 microCi of [ 3 H]AF 1890 in the absence or presence of excess unlabeled AF 1890 for 30 min at 31 degrees C. Autoradiographs showed a generalized distribution of silver grains over the seminiferous epithelium, in the tubular lumen, and in the interstitial spaces. In addition, clusters of grains were concentrated over the seminiferous epithelium in regions of spermatid heads and tails and in the basal portion of the Sertoli cell cytoplasm, and over Leydig cells in the interstitial space. The generalized distribution was reduced and the grain clusters eliminated by incubation in an excess of unlabeled AF 1890. [ 3 H]inulin was used to assess the effectiveness of the tubular ligation because inulin does not normally penetrate the blood-testis barrier. This extracellular marker was not localized in the tubular lumen or in the seminiferous epithelium. Therefore, the labeling observed with [ 3 H]AF 1890 indicates that this compound crosses the blood-testis barrier

A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole

Directory of Open Access Journals (Sweden)

Bianca Zingales

2015-05-01

Full Text Available Benznidazole (BZ is one of the two drugs used for Chagas disease treatment. Nevertheless therapeutic failures of BZ have been reported, which were mostly attributed to variable drug susceptibility among Trypanosoma cruzi strains. ATP-binding cassette (ABC transporters are involved in a variety of translocation processes and some members have been implicated in drug resistance. Here we report the characterisation of the first T. cruzi ABCG transporter gene, named TcABCG1, which is over-expressed in parasite strains naturally resistant to BZ. Comparison of TcABCG1 gene sequence of two TcI BZ-resistant strains with CL Brener BZ-susceptible strain showed several single nucleotide polymorphisms, which determined 11 amino acid changes. CL Brener transfected with TcI transporter genes showed 40-47% increased resistance to BZ, whereas no statistical significant increment in drug resistance was observed when CL Brener was transfected with the homologous gene. Only in the parasites transfected with TcI genes there was 2-2.6-fold increased abundance of TcABCG1 transporter protein. The analysis in wild type strains also suggests that the level of TcABCG1 transporter is related to BZ natural resistance. The characteristics of untranslated regions of TcABCG1 genes of BZ-susceptible and resistant strains were investigated by computational tools.

Structural Basis for Polypyrimidine Tract Recognition by the Essential Pre-mRNA Splicing Factor U2AF65

International Nuclear Information System (INIS)

Sickmier, E.; Frato, K.; Shen, H.; Paranawithana, S.; Green, M.; Kielkopf, C.

2006-01-01

The essential pre-mRNA splicing factor, U2AF 65 , guides the early stages of splice site choice by recognizing a polypyrimidine (Py)-tract consensus sequence near the 3'-splice site. Since Py-tracts are relatively poorly conserved in higher eukaryotes, U2AF 65 is faced with the problem of specifying uridine-rich sequences, yet tolerating a variety of nucleotide substitutions found in natural Py-tracts. To better understand these apparently contradictory RNA binding characteristics, the X-ray structure of the U2AF 65 RNA binding domain bound to a Py-tract composed of seven uridines has been determined at 2.5Angstroms resolution. Specific hydrogen bonds between U2AF 65 and the uracil bases provide an explanation for polyuridine recognition. Flexible sidechains and bound water molecules form the majority of the base contacts, and potentially could rearrange when the U2AF 65 structure adapts to different Py-tract sequences. The energetic importance of conserved residues for Py-tract binding is established by analysis of site-directed mutant U2AF 65 proteins using surface plasmon resonance

The naphthoquinones, vitamin K3 and its structural analog plumbagin, are substrates of the multidrug resistance-linked ABC drug transporter ABCG2

Science.gov (United States)

Shukla, Suneet; Wu, Chung-Pu; Nandigama, Krishnamachary; Ambudkar, Suresh V.

2008-01-01

Vitamin K3 (Menadione; 2-methyl-1,4-naphthoquinone) is a structural precursor of vitamins K1 and K2 which are essential for blood clotting. The naturally occurring structural analog of this vitamin, plumbagin (5-hydroxy-menadione), is known to modulate cellular proliferation, apoptosis, carcinogenesis, and radioresistance. We, here, report that both vitamin K3 and plumbagin are substrates of the multidrug resistance-linked ATP binding cassette (ABC) drug transporter, ABCG2. Vitamin K3 and plumbagin specifically inhibited the ABCG2-mediated efflux of mitoxantrone, but did not have any effect on the ABCB1-mediated efflux of rhodamine 123. This inhibition of ABCG2 function was due to their interaction at the substrate-binding site(s). They inhibited the binding of [125I]-Iodoarylazidoprazosin (IAAP), a substrate of ABCG2, to this transporter in a concentration-dependent manner with IC50 values of 7.3 and 22.6 μM, respectively, but had no effect on the binding of this photoaffinity analog to ABCB1. Both compounds stimulated ABCG2-mediated ATP hydrolysis and also inhibited the mitoxantrone-stimulated ATPase activity of this transporter, but did not have any significant effect on the ATPase activity of ABCB1. In a cytotoxicity assay, ABCG2-expressing HEK cells were 2.8- and 2.3-fold resistant to plumbagin and vitamin K3, respectively, compared to the control cells, suggesting that they are substrates of this transporter. Collectively, these data demonstrate for the first time that vitamin K3 is a substrate of the ABCG2 transporter. Thus, ABCG2 may have a role in the regulation of vitamin K3 levels in the body. In addition, vitamin K3 and its structural derivative, plumbagin, could potentially be used to modulate ABCG2 function. PMID:18065489

ABCG2/BCRP decreases the transfer of a food-born chemical carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in perfused term human placenta.

Science.gov (United States)

Myllynen, Päivi; Kummu, Maria; Kangas, Tiina; Ilves, Mika; Immonen, Elina; Rysä, Jaana; Pirilä, Rauna; Lastumäki, Anni; Vähäkangas, Kirsi H

2008-10-15

We have studied the role of ATP binding cassette (ABC) transporters in fetal exposure to carcinogens using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) a known substrate for ABC transporters as a model compound. In perfusion of human term placenta, transfer of (14)C-PhIP (2 microM) through the placenta resulted in fetal-to-maternal concentration ratio (FM ratio) of 0.72+/-0.09 at 6 h. The specific ABCG2 inhibitor KO143 increased the transfer of (14)C-PhIP from maternal to fetal circulation (FM ratio 0.90+/-0.08 at 6 h, p<0.05) while the ABCC1/ABCC2 inhibitor probenecid had no effect (FM ratio at 6 h 0.75+/-0.10, p=0.84). There was a negative correlation between the expression of ABCG2 protein in perfused tissue and the FM ratio of (14)C-PhIP (R=-0.81, p<0.01) at the end of the perfusion. The expression of ABCC2 protein did not correlate with FM ratio of PhIP (R: -0.11, p=0.76). In addition, PhIP induced the expression of ABC transporters in BeWo cells at mRNA level. In conclusion, our data indicates that ABCG2 decreases placental transfer of (14)C-PhIP in perfused human placenta. Also, PhIP may modify ABC transporter expression in choriocarcinoma cells.

Functional characterization of the copper transcription factor AfMac1 from Aspergillus fumigatus.

Science.gov (United States)

Park, Yong-Sung; Kim, Tae-Hyoung; Yun, Cheol-Won

2017-07-03

Although copper functions as a cofactor in many physiological processes, copper overload leads to harmful effects in living cells. Thus, copper homeostasis is tightly regulated. However, detailed copper metabolic pathways have not yet been identified in filamentous fungi. In this report, we investigated the copper transcription factor AfMac1 ( A spergillus f umigatus Mac1 homolog) and identified its regulatory mechanism in A. fumigatus AfMac1 has domains homologous to the DNA-binding and copper-binding domains of Mac1 from Saccharomyces cerevisiae , and AfMac1 efficiently complemented Mac1 in S. cerevisiae Expression of Afmac1 resulted in CTR1 up-regulation, and mutation of the DNA-binding domain of Afmac1 failed to activate CTR1 expression in S. cerevisiae The Afmac1 deletion strain of A. fumigatus failed to grow in copper-limited media, and its growth was restored by introducing ctrC We found that AfMac1 specifically bound to the promoter region of ctrC based on EMSA. The AfMac1-binding motif 5'-TGTGCTCA-3' was identified from the promoter region of ctrC , and the addition of mutant ctrC lacking the AfMac1-binding motif failed to up-regulate ctrC in A. fumigatus Furthermore, deletion of Afmac1 significantly reduced strain virulence and activated conidial killing activity by neutrophils and macrophages. Taken together, these results suggest that AfMac1 is a copper transcription factor that regulates cellular copper homeostasis in A. fumigatus . © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Dicty_cDB: Contig-U12802-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available cobacter cetorum strain MIT-0... 38 0.23 AF237484_1( AF237484 |pid:none) Dirofilaria immitis intermed...87 ( O97594 ) RecName: Full=Structural maintenance of chromosomes pro... 36 0.87 U00680_1( U00680 |pid:none) Brugia malayi intermed...1305( CP000879 |pid:none) Petrotoga mobilis SJ95, complet... 38 0.30 (Q9BZF9) RecName: Full=Uveal autoantigen with coiled...ns BAC clone RP11-764E7 from 2, complet... 34 0.79 6 ( FK620261 ) 454GmaGlobSeed354893 Soybean Seed...ditis elegans clone Y71H2X, *** SEQUENCI... 38 4.5 7 ( AC146972 ) Medicago truncatula clone mth2-128d9, compl

Unexpected Binding Mode of a Potent Indeno[1,2-b]indole-Type Inhibitor of Protein Kinase CK2 Revealed by Complex Structures with the Catalytic Subunit CK2α and Its Paralog CK2α′

Directory of Open Access Journals (Sweden)

Jennifer Hochscherf

2017-12-01

Full Text Available Protein kinase CK2, a member of the eukaryotic protein kinase superfamily, is associated with cancer and other human pathologies and thus an attractive drug target. The indeno[1,2-b]indole scaffold is a novel lead structure to develop ATP-competitive CK2 inhibitors. Some indeno[1,2-b]indole-based CK2 inhibitors additionally obstruct ABCG2, an ABC half transporter overexpressed in breast cancer and co-responsible for drug efflux and resistance. Comprehensive derivatization studies revealed substitutions of the indeno[1,2-b]indole framework that boost either the CK2 or the ABCG2 selectivity or even support the dual inhibition potential. The best indeno[1,2-b]indole-based CK2 inhibitor described yet (IC50 = 25 nM is 5-isopropyl-4-(3-methylbut-2-enyl-oxy-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione (4p. Herein, we demonstrate the membrane permeability of 4p and describe co-crystal structures of 4p with CK2α and CK2α′, the paralogs of human CK2 catalytic subunit. As expected, 4p occupies the narrow, hydrophobic ATP site of CK2α/CK2α′, but surprisingly with a unique orientation: its hydrophobic substituents point towards the solvent while its two oxo groups are hydrogen-bonded to a hidden water molecule. An equivalent water molecule was found in many CK2α structures, but never as a critical mediator of ligand binding. This unexpected binding mode is independent of the interdomain hinge/helix αD region conformation and of the salt content in the crystallization medium.

Exact solutions of sl-boson system in U(2l + 1) reversible O(2l + 2) transitional region

CERN Document Server

Zhang Xin

2002-01-01

Exact eigen-energies and the corresponding wavefunctions of the interacting sl-boson system in U(2l + 1) reversible O(2l +2) transitional region are obtained by using an algebraic Bethe Ansatz with the infinite dimensional Lie algebraic technique. Numerical algorithm for solving the Bethe Ansatz equations by using mathematical package is also outlined

The naphthoquinones, vitamin K3 and its structural analogue plumbagin, are substrates of the multidrug resistance linked ATP binding cassette drug transporter ABCG2.

Science.gov (United States)

Shukla, Suneet; Wu, Chung-Pu; Nandigama, Krishnamachary; Ambudkar, Suresh V

2007-12-01

Vitamin K3 (menadione; 2-methyl-1,4-naphthoquinone) is a structural precursor of vitamins K1 and K2, which are essential for blood clotting. The naturally occurring structural analogue of this vitamin, plumbagin (5-hydroxy-menadione), is known to modulate cellular proliferation, apoptosis, carcinogenesis, and radioresistance. We here report that both vitamin K3 and plumbagin are substrates of the multidrug resistance-linked ATP binding cassette drug transporter, ABCG2. Vitamin K3 and plumbagin specifically inhibited the ABCG2-mediated efflux of mitoxantrone but did not have any effect on the ABCB1-mediated efflux of rhodamine 123. This inhibition of ABCG2 function was due to their interaction at the substrate-binding site(s). Vitamin K3 and plumbagin inhibited the binding of [(125)I]iodoarylazidoprazosin, a substrate of ABCG2, to this transporter in a concentration-dependent manner with IC(50) values of 7.3 and 22.6 micromol/L, respectively, but had no effect on the binding of the photoaffinity analogue to ABCB1. Both compounds stimulated ABCG2-mediated ATP hydrolysis and also inhibited the mitoxantrone-stimulated ATPase activity of the ABCG2 transporter, but did not have any significant effect on the ATPase activity of ABCB1. In a cytotoxicity assay, ABCG2-expressing HEK cells were 2.8- and 2.3-fold resistant to plumbagin and vitamin K3, respectively, compared with the control cells, suggesting that they are substrates of this transporter. Collectively, these data show for the first time that vitamin K3 is a substrate of the ABCG2 transporter. Thus, ABCG2 may have a role in the regulation of vitamin K3 levels in the body. In addition, vitamin K3 and its structural derivative, plumbagin, could potentially be used to modulate ABCG2 function.

Lack of Abcg1 results in decreased plasma HDL cholesterol levels and increased biliary cholesterol secretion in mice fed a high cholesterol diet

NARCIS (Netherlands)

Wiersma, Harmen; Nijstad, Niels; de Boer, Jan Freark; Out, Ruud; Hogewerf, Wytse; Van Berkel, Theo J.; Kuipers, Folkert; Tietge, Uwe J. F.

Objective: The ATP Binding Cassette transporter G1 (ABCG1) has been implicated in cholesterol efflux towards HDL and reverse cholesterol transport (RCT). Biliary cholesterol secretion is considered as an important step in RCT. The aim of the present study was to determine the consequences of Abcg1

Tema 1: Programmering af robotenheder i grundskolen

Directory of Open Access Journals (Sweden)

Stine Ejsing-Duun

2016-01-01

Full Text Available I denne artikel undersøger vi potentialerne for at lære matematik gennem programmering af robotter. Vi foreslår en model med tre indbyrdes afhængige læringspotentialer, som programmering fordrer. Det omfatter elevens evne til at; (1 tænke i algoritmer, (2 producere viden og artefakter gennem brug af matematik og (3 foretage abstraktion og indkapsling. Programmering er blevet en del af grundskolens læringsmål i flere lande. I Danmark er programmering et læringsmål i forenklede fælles mål for Fysik/Kemi og desuden en del af den nationale undervisningsvejledning for matematik. En analyse af potentialerne i at anvende programmering i forbindelse med disse fag er derfor væsentlig. I denne artikel fokuserer vi på samspillet mellem matematik og programmering gennem litteraturstudier og analyse af empiriske situationer fra undervisning i programmering af LEGO Mindstorms. Teoretisk anvendes den instrumentelle tilgang til teknologi i matematikundervisning. Analysen viser en række måder, hvorpå didaktisk opmærksomhed på epistemisk forhandling kan understøtte læring af matematik gennem programmering.

Dicty_cDB: Contig-U05302-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available F275295 |AF275295.1 Eretmocerus queenslandensis clone 262Q c... 38 0.26 2 AF27529...4 |AF275294.1 Eretmocerus queenslandensis clone 171Q c... 38 0.26 2 AF275293 |AF275293.1 Eretmocerus queensland...ensis clone 168Qb ... 38 0.26 2 AF275292 |AF275292.1 Eretmocerus queenslandensis clone 168Qa ... 38 0.26 ...2 AF275291 |AF275291.1 Eretmocerus queenslandensis clone 165Qb ... 38 0.26 2 AF275290 |AF275290.1 Eretmocerus queensland...ensis clone 165Qa ... 38 0.26 2 AF275289 |AF275289.1 Eretmocerus queensland

ABCG2 inhibition as a therapeutic approach for overcoming ...

Indian Academy of Sciences (India)

2016-02-16

Feb 16, 2016 ... Breast cancer resistance protein (BCRP, ABCP or MXR)/ATP-binding cassette subfamily G member 2 (ABCG2) was characterized as a multidrug resistance efflux transporter in 1998. ABCG2 physiologically acts as a part of a self- defence mechanism for the organism; it enhances eliminating of toxic ...

ABCG2 Inhibition as a Therapeutic Approach for Overcoming ...

Indian Academy of Sciences (India)

Breast cancer resistance protein (BCRP, ABCP or MXR) / ATP-binding cassette subfamily G member 2 (ABCG2) was characterized as a multidrug resistance efflux transporter in 1998. ABCG2 physiologically acts as a part of a self-defense mechanism for the organism; it enhances eliminating of toxic xenobiotic substances ...

Vibrationally resolved photoionization of the 1σg and 1σu shells of N2 molecule

International Nuclear Information System (INIS)

Semenov, S K; Cherepkov, N A; Matsumoto, M; Fujiwara, K; Ueda, K; Kukk, E; Tahara, F; Sunami, T; Yoshida, H; Tanaka, T; Nakagawa, K; Kitajima, M; Tanaka, H; De Fanis, A

2006-01-01

Theoretical and experimental study of vibrationally resolved partial photoionization cross sections and angular asymmetry parameter β for the 1σ g and 1σ u shells of N 2 molecule in the region of the σ* shape resonance is reported. The measurements were made at the synchrotron radiation facility SPring-8 in Japan. The calculations in the random phase approximation have been performed using the relaxed core Hartree-Fock wavefunctions with the fractional charge of the ion core equal to 0.7. With its help, the role of interchannel coupling between the closely spaced 1σ g and 1σ u shells was studied. The experiment demonstrates the existence of a correlational maximum in the 1σ u shell photoionization cross section induced by the σ* shape resonance in the 1σ g shell. This maximum reveals itself even more clearly in the angular asymmetry parameter β for the v' = 0 and v' = 1 vibrational states of the ion. The calculation in the random phase approximation gives a consistent interpretation of the experimental data

Functional polymorphisms of the ABCG2 gene are associated with gout disease in the Chinese Han male population.

Science.gov (United States)

Zhou, Danqiu; Liu, Yunqing; Zhang, Xinju; Gu, Xiaoye; Wang, Hua; Luo, Xinhua; Zhang, Jin; Zou, Hejian; Guan, Ming

2014-05-22

Gout is a common type of arthritis that is characterized by hyperuricemia, tophi and joint inflammation. Genetic variations in the ABCG2 gene have been reported to influence serum uric acid levels and to participate in the pathogenesis of gout, but no further data have been reported in the Han Chinese population. Peripheral blood DNA was isolated from 352 male patients with gout and 350 gout-free normal male controls. High-resolution melting analysis and Sanger sequencing were performed to identify the genetic polymorphisms V12M, Q141K and Q126X in the ABCG2 gene. Genotype and haplotype analyses were utilized to determine the disease odds ratios (ORs). A prediction model for gout risk using ABCG2 protein function was established based on the genotype combination of Q126X and Q141K. For Q141K, the A allele frequency was 49.6% in the gout patients and 30.9% in the controls (OR 2.20, 95% confidence interval (CI): 1.77-2.74, p=8.99×10⁻¹³). Regarding Q126X, the T allele frequency was 4.7% in the gout patients and 1.7% in the controls (OR 2.91, 95% CI: 1.49-5.68, p=1.57×10⁻³). The A allele frequency for V12M was lower (18.3%) in the gout patients than in the controls (29%) (OR 0.55, 95% CI 0.43-0.71, p=2.55×10⁻⁶). In the order of V12M, Q126X and Q141K, the GCA and GTC haplotypes indicated increased disease risk (OR=2.30 and 2.71, respectively). Patients with mild to severe ABCG2 dysfunction accounted for 78.4% of gout cases. The ABCG2 126X and 141K alleles are associated with an increased risk of gout, whereas 12M has a protective effect on gout susceptibility in the Han Chinese population. ABCG2 dysfunction can be used to evaluate gout risk.

Inhibition of breast cancer resistance protein (ABCG2 in human myeloid dendritic cells induces potent tolerogenic functions during LPS stimulation.

Directory of Open Access Journals (Sweden)

Jun-O Jin

Full Text Available Breast cancer resistance protein (ABCG2, a member of the ATP-binding cassette transporters has been identified as a major determinant of multidrug resistance (MDR in cancer cells, but ABC transporter inhibition has limited therapeutic value in vivo. In this research, we demonstrated that inhibition of efflux transporters ABCG2 induced the generation of tolerogenic DCs from human peripheral blood myeloid DCs (mDCs. ABCG2 expression was present in mDCs and was further increased by LPS stimulation. Treatment of CD1c+ mDCs with an ABCG2 inhibitor, Ko143, during LPS stimulation caused increased production of IL-10 and decreased production of pro-inflammatory cytokines and decreased expression of CD83 and CD86. Moreover, inhibition of ABCG2 in monocyte-derived DCs (MDDCs abrogated the up-regulation of co-stimulatory molecules and production of pro-inflammatory cytokines in these cells in response to LPS. Furthermore, CD1c+ mDCs stimulated with LPS plus Ko143 inhibited the proliferation of allogeneic and superantigen-specific syngenic CD4+ T cells and promoted expansion of CD25+FOXP3+ regulatory T (Treg cells in an IL-10-dependent fashion. These tolerogenic effects of ABCG2 inhibition could be abolished by ERK inhibition. Thus, we demonstrated that inhibition of ABCG2 in LPS-stimulated mDCs can potently induce tolerogenic potentials in these cells, providing crucial new information that could lead to development of better strategies to combat MDR cancer.

Overcoming Multidrug Resistance via Photodestruction of ABCG2-Rich Extracellular Vesicles Sequestering Photosensitive Chemotherapeutics

Science.gov (United States)

Goler-Baron, Vicky; Assaraf, Yehuda G.

2012-01-01

Multidrug resistance (MDR) remains a dominant impediment to curative cancer chemotherapy. Efflux transporters of the ATP-binding cassette (ABC) superfamily including ABCG2, ABCB1 and ABCC1 mediate MDR to multiple structurally and functionally distinct antitumor agents. Recently we identified a novel mechanism of MDR in which ABCG2-rich extracellular vesicles (EVs) form in between attached neighbor breast cancer cells and highly concentrate various chemotherapeutics in an ABCG2-dependent manner, thereby sequestering them away from their intracellular targets. Hence, development of novel strategies to overcome MDR modalities is a major goal of cancer research. Towards this end, we here developed a novel approach to selectively target and kill MDR cancer cells. We show that illumination of EVs that accumulated photosensitive cytotoxic drugs including imidazoacridinones (IAs) and topotecan resulted in intravesicular formation of reactive oxygen species (ROS) and severe damage to the EVs membrane that is shared by EVs-forming cells, thereby leading to tumor cell lysis and the overcoming of MDR. Furthermore, consistent with the weak base nature of IAs, MDR cells that are devoid of EVs but contained an increased number of lysosomes, highly accumulated IAs in lysosomes and upon photosensitization were efficiently killed via ROS-dependent lysosomal rupture. Combining targeted lysis of IAs-loaded EVs and lysosomes elicited a synergistic cytotoxic effect resulting in MDR reversal. In contrast, topotecan, a bona fide transport substrate of ABCG2, accumulated exclusively in EVs of MDR cells but was neither detected in lysosomes of normal breast epithelial cells nor in non-MDR breast cancer cells. This exclusive accumulation in EVs enhanced the selectivity of the cytotoxic effect exerted by photodynamic therapy to MDR cells without harming normal cells. Moreover, lysosomal alkalinization with bafilomycin A1 abrogated lysosomal accumulation of IAs, consequently preventing

High ABCC2 and Low ABCG2 Gene Expression Are Early Events in the Colorectal Adenoma-Carcinoma Sequence

DEFF Research Database (Denmark)

Andersen, Vibeke; Vogel, Lotte K.; Kopp, Tine Iskov

2015-01-01

Development of colorectal cancer (CRC) may result from a dysfunctional interplay between diet, gut microbes and the immune system. The ABC transport proteins ABCB1 (P-glycoprotein, Multidrug resistance protein 1, MDR1), ABCC2 (MRP2) and ABCG2 (BCRP) are involved in transport of various compounds...

ABCG2 in peptic ulcer: gene expression and mutation analysis.

Science.gov (United States)

Salagacka-Kubiak, Aleksandra; Żebrowska, Marta; Wosiak, Agnieszka; Balcerczak, Mariusz; Mirowski, Marek; Balcerczak, Ewa

2016-08-01

The aim of this study was to evaluate the participation of polymorphism at position C421A and mRNA expression of the ABCG2 gene in the development of peptic ulcers, which is a very common and severe disease. ABCG2, encoded by the ABCG2 gene, has been found inter alia in the gastrointestinal tract, where it plays a protective role eliminating xenobiotics from cells into the extracellular environment. The materials for the study were biopsies of gastric mucosa taken during a routine endoscopy. For genotyping by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) at position C421A, DNA was isolated from 201 samples, while for the mRNA expression level by real-time PCR, RNA was isolated from 60 patients. The control group of healthy individuals consisted of 97 blood donors. The dominant genotype in the group of peptic ulcer patients and healthy individuals was homozygous CC. No statistically significant differences between healthy individuals and the whole group of peptic ulcer patients and, likewise, between the subgroups of peptic ulcer patients (infected and uninfected with Helicobacter pylori) were found. ABCG2 expression relative to GAPDH expression was found in 38 of the 60 gastric mucosa samples. The expression level of the gene varies greatly among cases. The statistically significant differences between the intensity (p = 0.0375) of H. pylori infection and ABCG2 gene expression have been shown. It was observed that the more intense the infection, the higher the level of ABCG2 expression.

Purification and characterization of a novel endo-β-1,4-glucanases , AfEG22, from the giant snail, Achatina fulica frussac.

Science.gov (United States)

Teng, Yigang; Yin, Qiuyu; ding, Ming; Zhao, Fukun

2010-10-01

In this study, we confirmed that at least three endo-β-1,4-glucanases existed in the digestive juice of the giant snail, Achatina fulica ferussac, by Congo red staining assay. One of these enzymes, a novel endo-β-1,4-glucanase (AfEG22), was purified 29.5-fold by gel filtration, anion exchange, and hydrophobic interaction chromatography. The carboxymethyl cellulose (CMC) hydrolytic activity of the purified enzyme was 12.3 U/mg protein. The molecular mass of AfEG22 was 22081 Da determined by MALDI-TOF. N-terminal amino acid sequencing revealed a sequence of EQRCTNQGGILKYYNT, which did not have significant homology with any proteins in BLAST database. The optimal pH and temperature for hydrolytic activity toward CMC were pH 4.0 and 50°C, respectively. AfEG22 was stable between pH 3.0 and pH 12.0 when incubated at 4°C for 3 h or at 37°C for 1 h. The enzyme remained more than 80% activity between pH 4.5 and pH 7.0 after incubation at 50°C for 1 h. AfEG22 possessed excellent thermostability as more than 70% activity was remained after incubation at 60°C for 3 h. Substrate specific analysis revealed that AfEG22 was a typical endo-β-1,4-glucanase. This is the first time to report a novel endo-β-1,4-glucanase with high stability from the digestive juice of A. fulica.

Ligand binding reduces SUMOylation of the peroxisome proliferator-activated receptor γ (PPARγ activation function 1 (AF1 domain.

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Rolf Diezko

Full Text Available Peroxisome proliferator-activated receptor gamma (PPARγ is a ligand-activated nuclear receptor regulating adipogenesis, glucose homeostasis and inflammatory responses. The activity of PPARγ is controlled by post-translational modifications including SUMOylation and phosphorylation that affects its biological and molecular functions. Several important aspects of PPARγ SUMOylation including SUMO isoform-specificity and the impact of ligand binding on SUMOylation remain unresolved or contradictory. Here, we present a comprehensive study of PPARγ1 SUMOylation. We show that PPARγ1 can be modified by SUMO1 and SUMO2. Mutational analyses revealed that SUMOylation occurs exclusively within the N-terminal activation function 1 (AF1 domain predominantly at lysines 33 and 77. Ligand binding to the C-terminal ligand-binding domain (LBD of PPARγ1 reduces SUMOylation of lysine 33 but not of lysine 77. SUMOylation of lysine 33 and lysine 77 represses basal and ligand-induced activation by PPARγ1. We further show that lysine 365 within the LBD is not a target for SUMOylation as suggested in a previous report, but it is essential for full LBD activity. Our results suggest that PPARγ ligands negatively affect SUMOylation by interdomain communication between the C-terminal LBD and the N-terminal AF1 domain. The ability of the LBD to regulate the AF1 domain may have important implications for the evaluation and mechanism of action of therapeutic ligands that bind PPARγ.

Dicty_cDB: Contig-U11778-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 43 2e-32 AF093214_1( AF093214 |pid:none) Hirtodrosophila pictiventris xanth... 14... 8e-30 AF543143_1( AF543143 |pid:none) Drosophila nannoptera strain 2 xan... 134 8e-30 AF058984_1( AF058984 |pid:none) Scaptodrosophi...la lebanonensis xant... 134 8e-30 AF543107_1( AF543107 |pid:none) Drosophila eremop

U(1) x SU(2) Chern-Simons gauge theory of underdoped cuprate superconductors

International Nuclear Information System (INIS)

Marchetti, P.A.; Su Zhao-Bin; Yu Lu

1998-05-01

The Chern-Simons bosonization with U(1)xSU(2) gauge field is applied to the 2-D t-J model in the limit t>>J, to study the normal state properties of underdoped cuprate superconductors. We prove the existence of an upper bound on the partition function for holons in a spinon background, and we find the optimal spinon configuration saturating the upper bound on average - a coexisting flux phase and s+id-like RVB state. After neglecting the feedback of holon fluctuations on the U(1) field B and spinon fluctuations on the SU(2) field V, the holon field is a fermion and the spinon field is a hard-core boson. Within this approximation we show that the B field produces a π flux phase for the holons, converting them into Dirac-like fermions, while the V field, taking into account the feedback of holons produces a gap for the spinons vanishing in the zero doping limit. The nonlinear σ-model with a mass term describes the crossover from the short-ranged antiferromagnetic (AF) state in doped samples to long range AF order in reference compounds. Moreover, we derive a low-energy effective action in terms of spinons holons and a self-generated U(1) gauge field. Neglecting the gauge fluctuations, the holons are described by the Fermi liquid theory with a Fermi surface consisting of 4 ''half-pockets'' centered at (+-π/2,+-π/2) and one reproduces the results for the electron spectral function obtained in the mean field approximation, in agreement with the photoemission data on underdoped cuprates. The gauge fluctuations are not confining due to coupling to holons, but nevertheless yield an attractive interaction between spinons and holons leading to a bound state with electron quantum numbers. The renormalisation effects due to gauge fluctuations give rise to non-Fermi liquid behaviour for the composite electron, in certain temperature range showing the linear in T resistivity. This formalism provides a new interpretation of the spin gap in the underdoped superconductors

Correlation of HIF-2α, ABCG2 and OCT-4 with chemotherapy resistance in human gastric cancer

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Hong-mei ZHANG

2015-11-01

Full Text Available Objective　To investigate the correlation of HIF-2α, ABCG2 and OCT-4 with chemotherapy resistant gastric cancer in humans. Methods　Fifty-two patients who were confirmed to have advanced gastric cancer with the aid of electronic endoscopy and pathology in the Department of Gastroenterology, Affiliated Hospital of Weifang Medical College, were enrolled in the study. According to the effect of FOL-FOX4 chemotherapy that these patients had experienced, they were divided into three groups: CR+PR (complete remission+partial remission group, SD (stable disease group and PD (progressive disease group. The expression levels of HIF-2α, ABCG2, and OCT-4 mRNA and protein were assessed in different groups by using RT-PCR and immunocytochemistry. Results　Two patients achieved CR , 19 achieved PR , 25 showed SD, and 6 showed PD. In other words, CR+PR were seen in 21 patients (40.4%, SD in 25(48.1%, PD in 6(11.5%. In CR+PR group, the expression levels of HIF-2α, ABCG2 and OCT4 mRNA and protein were low, but the above mentioned expressions were significantly increased in SD group and PD group. The expression levels of HIF-2α, ABCG2 and Oct-4 mRNA and protein were highest in the PD group, lower in the SD group, and lowest in the CR + PR groups (all P<0.05. Conclusions　The expression of the markers HIF-2α, ABCG2 and OCT4 in human tumor tissues is related to the effect of chemotherapy for gastric cancer. A high expression of tumor markers is perhaps the main reason for low efficacy of chemotherapy due to drug resistance. DOI: 10.11855/j.issn.0577-7402.2015.10.09

Bose-Fermi U(6/2j+1) supersymmetries and high-spin anomalies

International Nuclear Information System (INIS)

Morrison, I.; Jarvis, P.D.

1985-01-01

A supersymmetric extension of the interacting boson model (IBM) is constructed to describe high-spin anomalies in both even- and odd-mass spectra of the Hg, Pt region (190<=A<=200). Supergroup chains such as U(6/2j+1)containsOsp(6/2j+1)containsO(6)xSp(2j+1)... or U(6/2j+1)containsU(5/2j+1)xU(1)containsOsp(5/2j+1)... incorporate a single j-shell fermion in addition to the usual 's' and 'd' bosons (L=0 and L=2). The orthosympletic supergroup reflects the strong pairing force in the subspace of the fermion intruder level. The model agrees favourably with experiment and microscopic calculation. (orig.)

Expression of Potential Cancer Stem Cell Marker ABCG2 is Associated with Malignant Behaviors of Hepatocellular Carcinoma

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Guang Zhang

2013-01-01

Full Text Available Background. Despite improvement in treatment, the prognosis of hepatocellular carcinoma (HCC remains disastrous. Cancer stem cells (CSCs may be responsible for cancer malignant behaviors. ATP-binding cassette, subfamily G, member 2 (ABCG2 is widely expressed in both normal and cancer stem cells and may play an important role in cancer malignant behaviors. Methods. The expression of ABCG2 in HCC tissues and SMMC-7721 cells was examined, and the relevance of ABCG2 expression with clinical characteristics was analyzed. ABCG2+ and ABCG2− cells were sorted, and the potential of tumorigenicity was determined. Expression level of ABCG2 was manipulated by RNA interference and overexpression. Malignant behaviors including proliferation, drug resistance, migration, and invasion were studied in vitro. Results. Expression of ABCG2 was found in a minor group of cells in HCC tissues and cell lines. ABCG2 expression showed tendencies of association with unfavorable prognosis factors. ABCG2 positive cells showed a superior tumorigenicity. Upregulation of ABCG2 enhanced the capacity of proliferation, doxorubicin resistance, migration, and invasion potential, while downregulation of ABCG2 significantly decreased these malignant behaviors. Conclusion. Our results indicate that ABCG2 is a potential CSC marker for HCC. Its expression level has a close relationship with tumorigenicity, proliferation, drug resistance, and metastasis ability.

Non(anti)commutative N = (1,1/2) supersymmetric U(1) gauge theory

International Nuclear Information System (INIS)

Araki, Takeo; Ito, Katsushi; Ohtsuka, Akihisa

2005-01-01

We study a reduction of deformation parameters in non(anti)commutative N = 2 harmonic superspace to those in non(anti)commutative N = 1 superspace. By this reduction we obtain the exact gauge and supersymmetry transformations in the Wess-Zumino gauge of non(anti)commutative N = 2 supersymmetric U(1) gauge theory defined in the deformed harmonic superspace. We also find that the action with the first order correction in the deformation parameter reduces to the one in the N = 1 superspace by some field redefinition. We construct deformed N = (1,1/2) supersymmetry in N = 2 supersymmetric U(1) gauge theory in non(anti)commutative N = 1 superspace

Dicty_cDB: Contig-U12164-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available : (bits) Value AF325215_2( AF325215 |pid:none) Lymphocytic choriomeningitis virus... 39 0.27 AE014187_324( A...alciparum 3D7 chromo... 37 1.4 EU480452_2( EU480452 |pid:none) Lymphocytic choriomeningitis... virus... 36 1.8 AF325214_2( AF325214 |pid:none) Lymphocytic choriomeningitis virus... 36 2.3 ( P0...n BCN5; &A30481(A30481;S03779)... 35 5.1 Y16308_1( Y16308 |pid:none) Lymphocytic choriomeningitis...4188_497( AE014188 |pid:none) Plasmodium falciparum 3D7 chromo... 34 8.8 >AF325215_2( AF325215 |pid:none) Lymphocytic choriomeningiti

The Receptor-Binding Domain in the VP1u Region of Parvovirus B19.

Science.gov (United States)

Leisi, Remo; Di Tommaso, Chiarina; Kempf, Christoph; Ros, Carlos

2016-02-24

Parvovirus B19 (B19V) is known as the human pathogen causing the mild childhood disease erythema infectiosum. B19V shows an extraordinary narrow tissue tropism for erythroid progenitor cells in the bone marrow, which is determined by a highly restricted uptake. We have previously shown that the specific internalization is mediated by the interaction of the viral protein 1 unique region (VP1u) with a yet unknown cellular receptor. To locate the receptor-binding domain (RBD) within the VP1u, we analyzed the effect of truncations and mutations on the internalization capacity of the recombinant protein into UT7/Epo cells. Here we report that the N-terminal amino acids 5-80 of the VP1u are necessary and sufficient for cellular binding and internalization; thus, this N-terminal region represents the RBD required for B19V uptake. Using site-directed mutagenesis, we further identified a cluster of important amino acids playing a critical role in VP1u internalization. In silico predictions and experimental results suggest that the RBD is structured as a rigid fold of three α-helices. Finally, we found that dimerization of the VP1u leads to a considerably enhanced cellular binding and internalization. Taken together, we identified the RBD that mediates B19V uptake and mapped functional and structural motifs within this sequence. The findings reveal insights into the uptake process of B19V, which contribute to understand the pathogenesis of the infection and the neutralization of the virus by the immune system.

Expressions of ABCG2, CD133, and Podoplanin in Salivary Adenoid Cystic Carcinoma

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Wuwei Li

2014-01-01

Full Text Available Adenoid cystic carcinoma (ACC is one of the most common salivary gland malignant tumors with a high risk of recurrence and metastasis. Current studies on cancer stem cells (CSCs have verified that CSCs are the driving force behind tumor initiation and progression, suggesting that new cancer therapies may be established by effectively targeting and killing the CSCs. The primary goal of this study is to investigate the expression patterns of ABCG2, CD133, and podoplanin in ACC of minor salivary glands by immunohistochemistry analysis. We found that ABCG2 was weakly expressed in normal looking salivary gland tissues. A significant upregulation of ABCG2 expression in ACC was observed with a similar expression pattern of Ki-67. CD133 was detected in apical membrane of epithelial cells and podoplanin was expressed positively in myoepithelial cells of both normal looking tissue and ACC. However, no significant difference was found of the expression pattern of CD133 and podoplanin between normal looking tissues and ACC. Our observations suggest that CSCs may exist in quiescent cells with ABCG2 positive staining, which are surrounded by cells with positive expression of ABCG2 and Ki-67 in ACC, and costaining with ABCG2 and Ki-67 may help predict the location of CSCs.

Dicty_cDB: Contig-U16480-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 64 2e-08 AF021822_1( AF021822 |pid:none) Scaptodrosophila lebanonensis supe... 64 2e-08 DQ088819_1( DQ08881...ocheilonema viteae mRNA for ... 59 5e-07 AF021824_1( AF021824 |pid:none) Hirtodrosophila pictiventris super.

Dicty_cDB: Contig-U16444-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 001503 |pid:none) Burkholderia glumae BGR1 chromos... 130 5e-30 AF511570_1( AF511570 |pid:none) Uncultured soil...) Pseudomonas syringae pv. phaseo... 80 2e-13 AF511571_1( AF511571 |pid:none) Uncultured soil bacterium clon...00390 |pid:none) Mesorhizobium sp. BNC1, complete... 57 3e-09 AF511572_1( AF511572 |pid:none) Uncultured soil

Dicty_cDB: Contig-U05966-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available PCC 73102, c... 56 1e-11 AF079138_3( AF079138 |pid:none) Streptomyces venezuelae methymycin... 55 2e-11 AF15...) Gloeobacter violaceus PCC 7421 ... 65 2e-11 AF015823_1( AF015823 |pid:none) Streptomyces venezuelae venA g

Determination of co-metabolism for 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (DDT) degradation with enzymes from Trametes versicolor U97.

Science.gov (United States)

Sari, Ajeng Arum; Tachibana, Sanro; Itoh, Kazutaka

2012-08-01

Trametes versicolor U97 isolated from nature degraded 73% of the 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (DDT) in a malt extract liquid medium after a 40-d incubation period. This paper presents a kinetic study of microbial growth using the Monod equation. T. versicolor U97 degraded DDT during an exponential growth phase, using glucose as a carbon source for growth. The growth of T. versicolor U97 was not affected by DDT. DDT was degraded by T. versicolor U97 only when the secondary metabolism coincided with the production of several enzymes. Furthermore, modeling of several inhibitors using the partial least squares function in Minitab 15, revealed lignin peroxidase (98.7 U/l) plays a role in the degradation of DDT. T. versicolor U97 produced several metabolites included a single-ring aromatic compound, 4-chlorobenzoic acid. Copyright © 2012 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Down-regulation of ABCG2, a urate exporter, by parathyroid hormone enhances urate accumulation in secondary hyperparathyroidism.

Science.gov (United States)

Sugimoto, Ryusei; Watanabe, Hiroshi; Ikegami, Komei; Enoki, Yuki; Imafuku, Tadashi; Sakaguchi, Yoshiaki; Murata, Michiya; Nishida, Kento; Miyamura, Shigeyuki; Ishima, Yu; Tanaka, Motoko; Matsushita, Kazutaka; Komaba, Hirotaka; Fukagawa, Masafumi; Otagiri, Masaki; Maruyama, Toru

2017-03-01

Hyperuricemia occurs with increasing frequency among patients with hyperparathyroidism. However, the molecular mechanism by which the serum parathyroid hormone (PTH) affects serum urate levels remains unknown. This was studied in uremic rats with secondary hyperparathyroidism where serum urate levels were found to be increased and urate excretion in the intestine and kidney decreased, presumably due to down-regulation of the expression of the urate exporter ABCG2 in intestinal and renal epithelial membranes. These effects were prevented by administration of the calcimimetic cinacalcet, a PTH suppressor, suggesting that PTH may down-regulate ABCG2 expression. This was directly tested in intestinal Caco-2 cells where the expression of ABCG2 on the plasma membrane was down-regulated by PTH (1-34) while its mRNA level remained unchanged. Interestingly, an inactive PTH derivative (13-34) had no effect, suggesting that a posttranscriptional regulatory system acts through the PTH receptor to regulate ABCG2 plasma membrane expression. As found in an animal study, additional clinical investigations showed that treatment with cinacalcet resulted in significant reductions in serum urate levels together with decreases in PTH levels in patients with secondary hyperparathyroidism undergoing dialysis. Thus, PTH down-regulates ABCG2 expression on the plasma membrane to suppress intestinal and renal urate excretion, and the effects of PTH can be prevented by cinacalcet treatment. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Dicty_cDB: Contig-U10497-1 [Dicty_cDB

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Full Text Available ce 9 from Patent WO0234921. ... 79 2e-13 AF511570_1( AF511570 |pid:none) Uncultured soil bacterium clone 57....000542_2092( CP000542 |pid:none) Verminephrobacter eiseniae EF01... 58 4e-07 AF511571_1( AF511571 |pid:none) Uncultured soil... Pseudomonas fluorescens Pf0-1, ... 51 7e-05 AF511572_1( AF511572 |pid:none) Uncultured soil bacterium clone

Structural basis of small-molecule inhibition of human multidrug transporter ABCG2

DEFF Research Database (Denmark)

Jackson, Scott M; Manolaridis, Ioannis; Kowal, Julia

2018-01-01

requires high-resolution structural insight. Here, we present cryo-EM structures of human ABCG2 bound to synthetic derivatives of the fumitremorgin C-related inhibitor Ko143 or the multidrug resistance modulator tariquidar. Both compounds are bound to the central, inward-facing cavity of ABCG2, blocking...

Dicty_cDB: Contig-U15137-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available ne) Phalaenopsis sp. 'KCbutterfly' put... 65 2e-09 ( O22655 ) RecName: Full=Profi... AF049936_1( AF049936 |pid:none) Petunia x hybrida PGPS/NH20 (PGPS/... 65 2e-09 AF126263_1( AF126263 |pid:no

Path integral for coherent states of the dynamical U2 group and U2/1 supergroup

International Nuclear Information System (INIS)

Kochetov, E.A.

1992-01-01

A part-integral formulation in the representation of coherent states for the unitary U 2 group and U 2/1 supergroup is introduced. U 2 and U 2/1 path integrals are shown to be defined on the coset spaces U 2 /U 1 xU 1 and U 2/1 /U 1/1 xU 1 , respectively. These coset appears as curved classical phase spaces. Partition functions are expressed as path integrals over these spaces. In the case when U 2 and U 2/1 are the dynamical groups, the corresponding path integrals are evaluated with the help of linear fractional transformations that appear as the group (supergroup) action in the coset space (superspace). Possible applications for quantum models are discussed. 9 refs

Structure and function of ABCG2-rich extracellular vesicles mediating multidrug resistance.

Directory of Open Access Journals (Sweden)

Vicky Goler-Baron

2011-01-01

Full Text Available Multidrug resistance (MDR is a major impediment to curative cancer chemotherapy. The ATP-Binding Cassette transporters ABCG2, ABCB1 and ABCC2 form a unique defense network against multiple structurally and functionally distinct chemotherapeutics, thereby resulting in MDR. Thus, deciphering novel mechanisms of MDR and their overcoming is a major goal of cancer research. Recently we have shown that overexpression of ABCG2 in the membrane of novel extracellular vesicles (EVs in breast cancer cells results in mitoxantrone resistance due to its dramatic sequestration in EVs. However, nothing is known about EVs structure, biogenesis and their ability to concentrate multiple antitumor agents. To this end, we here found that EVs are structural and functional homologues of bile canaliculi, are apically localized, sealed structures reinforced by an actin-based cytoskeleton and secluded from the extracellular milieu by the tight junction proteins occludin and ZO-1. Apart from ABCG2, ABCB1 and ABCC2 were also selectively targeted to the membrane of EVs. Moreover, Ezrin-Radixin-Moesin protein complex selectively localized to the border of the EVs membrane, suggesting a key role for the tethering of MDR pumps to the actin cytoskeleton. The ability of EVs to concentrate and sequester different antitumor drugs was also explored. Taking advantage of the endogenous fluorescence of anticancer drugs, we found that EVs-forming breast cancer cells display high level resistance to topotecan, imidazoacridinones and methotrexate via efficient intravesicular drug concentration hence sequestering them away from their cellular targets. Thus, we identified a new modality of anticancer drug compartmentalization and resistance in which multiple chemotherapeutics are actively pumped from the cytoplasm and highly concentrated within the lumen of EVs via a network of MDR transporters differentially targeted to the EVs membrane. We propose a composite model for the structure and

Dicty_cDB: Contig-U13870-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available yces hygroscopicus strain ... 86 3e-15 AF015823_1( AF015823 |pid:none) Streptomyces venezuelae venA gene,......e-13 AF079138_6( AF079138 |pid:none) Streptomyces venezuelae methymycin... 77 1e-...one) Mycobacterium bovis subsp. bovis... 73 2e-11 AF079138_3( AF079138 |pid:none) Streptomyces venezuelae me

Assessment of ABCG2-mediated transport of pesticides across the rabbit placenta barrier using a novel MDCKII in vitro model

International Nuclear Information System (INIS)

Halwachs, Sandra; Schäfer, Ingo; Kneuer, Carsten; Seibel, Peter; Honscha, Walther

2016-01-01

In humans, the ATP-binding cassette efflux transporter ABCG2 contributes to the fetoprotective barrier function of the placenta, potentially limiting the toxicity of transporter substrates to the fetus. During testing of chemicals including pesticides, developmental toxicity studies are performed in rabbit. Despite its toxicological relevance, ABCG2-mediated transport of pesticides in rabbit placenta has not been yet elucidated. We therefore generated polarized MDCK II cells expressing the ABCG2 transporter from rabbit placenta (rbABCG2) and evaluated interaction of the efflux transporter with selected insecticides, fungicides, and herbicides. The Hoechst H33342 accumulation assay indicated that 13 widely used pesticidal active substances including azoxystrobin, carbendazim, chlorpyrifos, chlormequat, diflufenican, dimethoate, dimethomorph, dithianon, ioxynil, methiocarb, propamocarb, rimsulfuron and toclofos-methyl may be rbABCG2 inhibitors and/or substrates. No such evidence was obtained for chlorpyrifos-methyl, epoxiconazole, glyphosate, imazalil and thiacloprid. Moreover, chlorpyrifos (CPF), dimethomorph, tolclofos-methyl and rimsulfuron showed concentration-dependent inhibition of H33342 excretion in rbABCG2-transduced MDCKII cells. To further evaluate the role of rbABCG2 in pesticide transport across the placenta barrier, we generated polarized MDCKII-rbABCG2 monolayers. Confocal microscopy confirmed correct localization of rbABCG2 protein in the apical plasma membrane. In transepithelial flux studies, we showed the time-dependent preferential basolateral to apical (B > A) directed transport of [ 14 C] CPF across polarized MDCKII-rbABCG2 monolayers which was significantly inhibited by the ABCG2 inhibitor fumitremorgin C (FTC). Using this novel in vitro cell culture model, we altogether showed functional secretory activity of the ABCG2 transporter from rabbit placenta and identified several pesticides like the insecticide CPF as potential rbABCG2 substrates

Assessment of ABCG2-mediated transport of pesticides across the rabbit placenta barrier using a novel MDCKII in vitro model

Energy Technology Data Exchange (ETDEWEB)

Halwachs, Sandra [Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Universität Leipzig, Leipzig (Germany); Schäfer, Ingo [Molecular Cell Therapy, Center for Biotechnology and Biomedicine, Faculty of Medicine, Universität Leipzig, Leipzig (Germany); Kneuer, Carsten [Federal Institute for Risk Assessment (BfR), Pesticide Safety, Max-Dohrn-Straße 8-10, D-10589 Berlin (Germany); Seibel, Peter [Molecular Cell Therapy, Center for Biotechnology and Biomedicine, Faculty of Medicine, Universität Leipzig, Leipzig (Germany); Honscha, Walther, E-mail: honscha@vetmed.uni-leipzig.de [Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Universität Leipzig, Leipzig (Germany)

2016-08-15

In humans, the ATP-binding cassette efflux transporter ABCG2 contributes to the fetoprotective barrier function of the placenta, potentially limiting the toxicity of transporter substrates to the fetus. During testing of chemicals including pesticides, developmental toxicity studies are performed in rabbit. Despite its toxicological relevance, ABCG2-mediated transport of pesticides in rabbit placenta has not been yet elucidated. We therefore generated polarized MDCK II cells expressing the ABCG2 transporter from rabbit placenta (rbABCG2) and evaluated interaction of the efflux transporter with selected insecticides, fungicides, and herbicides. The Hoechst H33342 accumulation assay indicated that 13 widely used pesticidal active substances including azoxystrobin, carbendazim, chlorpyrifos, chlormequat, diflufenican, dimethoate, dimethomorph, dithianon, ioxynil, methiocarb, propamocarb, rimsulfuron and toclofos-methyl may be rbABCG2 inhibitors and/or substrates. No such evidence was obtained for chlorpyrifos-methyl, epoxiconazole, glyphosate, imazalil and thiacloprid. Moreover, chlorpyrifos (CPF), dimethomorph, tolclofos-methyl and rimsulfuron showed concentration-dependent inhibition of H33342 excretion in rbABCG2-transduced MDCKII cells. To further evaluate the role of rbABCG2 in pesticide transport across the placenta barrier, we generated polarized MDCKII-rbABCG2 monolayers. Confocal microscopy confirmed correct localization of rbABCG2 protein in the apical plasma membrane. In transepithelial flux studies, we showed the time-dependent preferential basolateral to apical (B > A) directed transport of [{sup 14}C] CPF across polarized MDCKII-rbABCG2 monolayers which was significantly inhibited by the ABCG2 inhibitor fumitremorgin C (FTC). Using this novel in vitro cell culture model, we altogether showed functional secretory activity of the ABCG2 transporter from rabbit placenta and identified several pesticides like the insecticide CPF as potential rbABCG2

Abcg5/Abcg8-independent pathways contribute to hepatobiliary cholesterol secretion in mice

NARCIS (Netherlands)

Plosch, Torsten; van der Veen, Jelske N.; Havinga, Rick; Huijkman, Nicolette C. A.; Bloks, Vincent W.; Kuipers, Folkert

The ATP-binding cassette (ABC) half-transporters ABCG5 and ABCG8 heterodimerize into a functional complex that mediates the secretion of plant sterols and cholesterol by hepatocytes into bile and their apical efflux from enterocytes. We addressed the putative rate-controlling role of Abcg5/Abcg8 in

Effect of ABCG2/BCRP Expression on Efflux and Uptake of Gefitinib in NSCLC Cell Lines.

Directory of Open Access Journals (Sweden)

Maricla Galetti

Full Text Available BCRP/ABCG2 emerged as an important multidrug resistance protein, because it confers resistance to several classes of cancer chemotherapeutic agents and to a number of novel molecularly-targeted therapeutics such as tyrosine kinase inhibitors. Gefitinib is an orally active, selective EGFR tyrosine kinase inhibitor used in the treatment of patients with advanced non small cell lung cancer (NSCLC carrying activating EGFR mutations. Membrane transporters may affect the distribution and accumulation of gefitinib in tumour cells; in particular a reduced intracellular level of the drug may result from poor uptake, enhanced efflux or increased metabolism.The present study, performed in a panel of NSCLC cell lines expressing different ABCG2 plasma membrane levels, was designed to investigate the effect of the efflux transporter ABCG2 on intracellular gefitinib accumulation, by dissecting the contribution of uptake and efflux processes.Our findings indicate that gefitinib, in lung cancer cells, inhibits ABCG2 activity, as previously reported. In addition, we suggest that ABCG2 silencing or overexpression affects intracellular gefitinib content by modulating the uptake rather than the efflux. Similarly, overexpression of ABCG2 affected the expression of a number of drug transporters, altering the functional activities of nutrient and drug transport systems, in particular inhibiting MPP, glucose and glutamine uptake.Therefore, we conclude that gefitinib is an inhibitor but not a substrate for ABCG2 and that ABCG2 overexpression may modulate the expression and activity of other transporters involved in the uptake of different substrates into the cells.

Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells

DEFF Research Database (Denmark)

Ozvegy, C.; Litman, Thomas; Szakacs, G.

2001-01-01

ABCG2 (also called MXR (3), BCRP (4), or ABCP (5) is a recently-identified ABC half-transporter, which causes multidrug resistance in cancer. Here we report that the expression of the ABCG2 protein in Sf9 insect cells resulted in a high-capacity, vanadate-sensitive ATPase activity in isolated...

ROLE OF ATP BINDING CASSETTE SUB-FAMILY MEMBER 2 (ABCG2) IN MOUSE EMBRYONIC STEM CELL DEVELOPMENT.

Science.gov (United States)

ATP binding cassette sub-family member 2 (ABCG2), is a member of the ABC transporter superfamily and a principal xenobiotic transporter. ABCG2 is also highly expressed in certain stem cell populations where it is thought to be related to stem cell plasticity, although the role o...

Dicty_cDB: Contig-U11746-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available F459463_1( AF459463 |pid:none) Uncultured environmental landfill ... 125 2e-27 (Q043I0) RecName: Full=Format...ne) Uncultured environmental landfill ... 115 3e-24 (Q04FS6) RecName: Full=Formate--tetrahydrofolate ligase;...me: Full=Formate--tetrahydrofolate ligase; ... 110 6e-23 AF459459_1( AF459459 |pid:none) Uncultured environmental landfill...none) Uncultured bacterium gene for puta... 105 3e-21 AF459462_1( AF459462 |pid:none) Uncultured environmental landfill

Study of infrared emission spectroscopy for the B1Δg–A1Πu and B′1Σg+–A1Πu systems of C2

International Nuclear Information System (INIS)

Chen, Wang; Kawaguchi, Kentarou; Tang, Jian; Bernath, Peter F.

2016-01-01

Thirteen bands for the B 1 Δ g –A 1 Π u system and eleven bands for the B ′1 Σ g + –A 1 Π u system of C 2 were identified in the Fourier transform infrared emission spectra of hydrocarbon discharges. The B ′1 Σ g + v = 4 and the B 1 Δ g v = 6, 7, and 8 vibrational levels involved in nine bands were studied for the first time. A direct global analysis with Dunham parameters was carried out satisfactorily for the B 1 Δ g –A 1 Π u system except for a small perturbation in the B 1 Δ g v = 6 level. The calculated rovibrational term energies up to B 1 Δ g v = 12 showed that the level crossing between the B 1 Δ g and d 3 Π g states is responsible for many of the prominent perturbations in the Swan system observed previously. Nineteen forbidden transitions of the B 1 Δ g –a 3 Π u transition were identified and the off-diagonal spin-orbit interaction constant A dB between d 3 Π g and B 1 Δ g was derived as 8.3(1) cm −1 . For the B ′1 Σ g + –A 1 Π u system, only individual band analyses for each vibrational level in the B′ 1 Σ g + state could be done satisfactorily and Dunham parameters obtained from these effective parameters showed that the anharmonic vibrational constant ω e x e is anomalously small (nearly zero). Inspection of the RKR (Rydberg-Klein-Rees) potential curves for the B ′1 Σ g + and X 1 Σ g + states revealed that an avoided crossing or nearly avoided crossing may occur around 30 000 cm −1 , which is responsible for the anomalous molecular constants in these two states

Dicty_cDB: Contig-U16120-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available lasmodium falciparum strain SEN16 from Senegal C... 32 1.5 3 ( AF134666 ) Plasmodium falciparum strain IVC3 ...patent US 7365185. 30 2.6 5 ( AF134680 ) Plasmodium falciparum strain SEN23 from Senegal C... 32 2.6 4 ( AF1...atus clone R3-12D17, WOR... 38 2.6 9 ( AF134678 ) Plasmodium falciparum strain SEN12 from Senegal...rain EQG2 from Equatorial... 32 3.0 4 ( AF134687 ) Plasmodium falciparum strain SEN13 from Senegal C... 32 3...lciparum strain SEN10 from Senegal C... 32 3.7 3 ( AC174290 ) Medicago truncatula clone mth2-52e11, complete

Dicty_cDB: Contig-U13293-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 093214_1( AF093214 |pid:none) Hirtodrosophila pictiventris xanth... 206 6e-52 FB7...23 |pid:none) Sequence 7019 from Patent WO200903... 191 2e-47 AF058984_1( AF058984 |pid:none) Scaptodrosophila

Dicty_cDB: Contig-U12133-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available mplicated in... 40 1.0 2 ( AX683150 ) Sequence 124 from Patent EP1279744. 40 1.0 2 ( L27127 ) Drosophila melanogaster imitation...none) Trypanosoma brucei chromosome 2 cl... 122 5e-30 AF292095_1( AF292095 |pid:none) Xenopus laevis imitation

Activity of ABCG2 Is Regulated by Its Expression and Localization in DHT and Cyclopamine-Treated Breast Cancer Cells.

Science.gov (United States)

Chua, Vivian Y L; Larma, Irma; Harvey, Jennet; Thomas, Marc A; Bentel, Jacqueline M

2016-10-01

Elevated expression of the efflux transporter, ATP-binding cassette subfamily G isoform 2 (ABCG2) on the plasma membrane of cancer cells contributes to the development of drug resistance and is a key characteristic of cancer stem cells. In this study, gene expression analysis identified that treatment of the MCF-7 and T-47D breast cancer cell lines with the androgen, 5α-dihydrotestosterone (DHT), and the Hedgehog signaling inhibitor, cyclopamine downregulated ABCG2 mRNA levels. In MCF-7 cells, and in Hoechst 33342(lo) /CD44(hi) /CD24(lo) breast cancer stem-like cells isolated from MCF-7 cultures, ABCG2 was accumulated in cell-to-cell junction complexes and in large cytoplasmic aggresome-like vesicles. DHT treatments, which decreased cellular ABCG2 protein levels, led to diminished ABCG2 localization in both cell-to-cell junction complexes and in cytoplasmic vesicles. In contrast, cyclopamine, which did not alter ABCG2 protein levels, induced accumulation of ABCG2 in cytoplasmic vesicles, reducing its localization in cell-to-cell junction complexes. The reduced localization of ABCG2 at the plasma membrane of MCF-7 cells was associated with decreased efflux of the ABCG2 substrate, mitoxantrone, and increased sensitivity of cyclopamine-treated cultures to the cytotoxic effects of mitoxantrone. Together, these findings indicate that DHT and cyclopamine reduce ABCG2 activity in breast cancer cells by distinct mechanisms, providing evidence to advocate the adjunct use of analogous pharmaceutics to increase or prolong the efficacy of breast cancer treatments. J. Cell. Biochem. 117: 2249-2259, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Dicty_cDB: Contig-U02161-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 467571094 Global-Ocean-Sampling_GS-31-01-01-1... 30 7.4 4 ( AC155803 ) Medicago truncatula clone mth2-103j6, compl...01349 |pid:none) Methylobacterium nodulans ORS 2... 52 4e-05 AF129085_1( AF129085 |pid:none) Homo sapiens carboxy term...00928. 34 0.23 10 ( EJ664173 ) 1092955035499 Global-Ocean-Sampling_GS-30-02-01-1... 48 0.27 2 ( EJ677170 ) 1...092955092857 Global-Ocean-Sampling_GS-30-02-01-1... 48 0.27 2 ( AF063866 ) Melanoplus sanguinipes entomopoxvirus, compl..., WORKING D... 38 0.47 7 ( EJ269942 ) 1095353004341 Global-Ocean-Sampling_GS-27-0

Dicty_cDB: Contig-U16421-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available _1( AF155058 |pid:none) Israeli tick typhus rickettsia pro... 38 3.2 CP000698_305...rotein PS 12... 39 2.4 DQ097084_1( DQ097084 |pid:none) Rickettsia mongolotimonae isolate ... 38 3.2 AF155058

Magnetic and crystallographic properties of Gd(Cu/sub 1-x/Ni/sub x/)2 and Gd(Cu/sub 1-x/Al/sub x/)2 intermetallic compounds

International Nuclear Information System (INIS)

Borombaev, M.K.; Levitin, R.Z.; Markosyan, A.S.; Snegirev, V.V.

1986-01-01

Magnetization, paramagnetic susceptibility, and temperature dependence of lattice parameters of Gd(Cu/sub 1-x/Ni/sub x/) 2 (0 2 (0 2 -type structure have been studied in a wide range of temperatures. Below the ordering temperature anomalies in thermal expansion along the crystallographic axes a, b, and c enabled to distinguish between various types of magnetic arrangements. The Gd(Cu/sub 1-x/Ni/sub x/) 2 system has two types of antiferromagnetic phases: AF1 (0 = 0.13 the system orders ferromagnetically. In the Gd(Cu/sub 1-x/Al/sub x/) 2 system two magnetic phases AF1 and AF3 occur in the concentration regions 0 <= x <= 0.035 and 0.04 <= x <= 0.07, respectively. The obtained results are discussed in terms of the RKKY model via the changing conduction electron concentration. (author)

ATP binding cassette G1-dependent cholesterol efflux during inflammation.

Science.gov (United States)

de Beer, Maria C; Ji, Ailing; Jahangiri, Anisa; Vaughan, Ashley M; de Beer, Frederick C; van der Westhuyzen, Deneys R; Webb, Nancy R

2011-02-01

ATP binding cassette transporter G1 (ABCG1) mediates the transport of cellular cholesterol to HDL, and it plays a key role in maintaining macrophage cholesterol homeostasis. During inflammation, HDL undergoes substantial remodeling, acquiring lipid changes and serum amyloid A (SAA) as a major apolipoprotein. In the current study, we investigated whether remodeling of HDL that occurs during acute inflammation impacts ABCG1-dependent efflux. Our data indicate that lipid free SAA acts similarly to apolipoprotein A-I (apoA-I) in mediating sequential efflux from ABCA1 and ABCG1. Compared with normal mouse HDL, acute phase (AP) mouse HDL containing SAA exhibited a modest but significant 17% increase in ABCG1-dependent efflux. Interestingly, AP HDL isolated from mice lacking SAA (SAAKO mice) was even more effective in promoting ABCG1 efflux. Hydrolysis with Group IIA secretory phospholipase A(2) (sPLA(2)-IIA) significantly reduced the ability of AP HDL from SAAKO mice to serve as a substrate for ABCG1-mediated cholesterol transfer, indicating that phospholipid (PL) enrichment, and not the presence of SAA, is responsible for alterations in efflux. AP human HDL, which is not PL-enriched, was somewhat less effective in mediating ABCG1-dependent efflux compared with normal human HDL. Our data indicate that inflammatory remodeling of HDL impacts ABCG1-dependent efflux independent of SAA.

SU(2) x U(1) x U'(1) models which are slightly different from the Weinberg-Salam model

International Nuclear Information System (INIS)

Gao, C.; Wu, D.

1981-01-01

We discuss SU(2) x U(1) x U'(1) models by a uniform formula which is convenient for their comparison with the standard Weinberg-Salam model. As examples, we give three interesting models which are based on different grand unification models. In one model, U'(1) does not contribute to the electromagnetic interaction; in the other two, both U(1) and U'(1) do contribute to the electromagnetic interaction. Also, the first two models can approach the standard Weinberg-Salam model as close as one wants; but the third model has limitations on it

Dicty_cDB: Contig-U03221-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available e) Botryotinia fuckeliana polyketide ... 53 2e-05 AF079138_6( AF079138 |pid:none) Streptomyces venezuelae me...id:none) Saccharopolyspora erythraea NRR... 52 5e-05 AF079138_3( AF079138 |pid:none) Streptomyces venezuelae...Gibberella moniliformis polyketide... 51 8e-05 AF015823_1( AF015823 |pid:none) Streptomyces venezuelae venA

Dicty_cDB: Contig-U14994-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 93 |pid:none) Borrelia hermsii putative lipoprot... 37 2.3 EF583007_1( EF583007 |pid:none) Simian rotavirus ...sid protein VP2; &L33364_1(L333... 36 6.6 AF474406_1( AF474406 |pid:none) Simian rotavirus SA11 C13 inner ca

Heat shock protein 27-derived atheroprotection involves reverse cholesterol transport that is dependent on GM-CSF to maintain ABCA1 and ABCG1 expression in ApoE-/- mice.

Science.gov (United States)

Pulakazhi Venu, Vivek Krishna; Adijiang, Ayinuer; Seibert, Tara; Chen, Yong-Xiang; Shi, Chunhua; Batulan, Zarah; O'Brien, Edward R

2017-06-01

Recently, we demonstrated that heat shock protein (HSP)-27 is protective against the development of experimental atherosclerosis, reducing plaque cholesterol content by more than 30%. Moreover, elevated HSP-27 levels are predictive of relative freedom from clinical cardiovascular events. HSP-27 signaling occurs via the activation of NF-κB, which induces a marked up-regulation in expression of granulocyte-monocyte colony-stimulating factor (GM-CSF), a cytokine that is known to alter ABC transporters involved in reverse cholesterol transport (RCT). Therefore, we hypothesized that HSP-27-derived GM-CSF has a potent role in impeding plaque formation by promoting macrophage RCT and sought to better characterize this pathway. Treatment of THP-1 cells, RAW-Blue cells, and primary macrophages with recombinant HSP-27 resulted in NF-κB activation via TLR-4 and was inhibited by various pharmacologic blockers of this pathway. Moreover, HSP-27-induced upregulation of GM-CSF expression was dependent on TLR-4 signaling. Recombinant (r)HSP-27 treatment of ApoE -/- female (but not male) mice for 4 wk yielded reductions in plaque area and cholesterol clefts of 33 and 47%, respectively, with no effect on GM-CSF -/- ApoE -/- mice. With 12 wk of rHSP-27 treatment, both female and male mice showed reductions in plaque burden (55 and 42%, respectively) and a 60% reduction in necrotic core area but no treatment effect in GM-CSF -/- ApoE -/- mice. In vitro functional studies revealed that HSP-27 enhanced the expression of ABCA1 and ABCG1, as well as facilitated cholesterol efflux in vitro by ∼10%. These novel findings establish a paradigm for HSP-27-mediated RCT and set the stage for the development of HSP-27 atheroprotective therapeutics.-Pulakazhi Venu, V. K., Adijiang, A., Seibert, T., Chen, Y.-X., Shi, C., Batulan, Z., O'Brien, E. R. Heat shock protein 27-derived atheroprotection involves reverse cholesterol transport that is dependent on GM-CSF to maintain ABCA1 and ABCG1

Localization of the ABCG2 mitoxantrone resistance-associated protein in normal tissues

DEFF Research Database (Denmark)

Fetsch, Patricia A; Abati, Andrea; Litman, Thomas

2006-01-01

was consistently found in alveolar pneumocytes, sebaceous glands, transitional epithelium of bladder, interstitial cells of testes, prostate epithelium, endocervical cells of uterus, squamous epithelium of cervix, small and large intestinal mucosa/epithelial cells, islet and acinar cells of pancreas, zona...... ABCG2 have a significant secretory function. These data suggest a dual function for ABCG2 in some tissues: the excretion of toxins and xenobiotics including anti-cancer agents and a potential, as-yet undefined role in the secretion of endogenous substrates....

ABCG2 inhibition as a therapeutic approach for overcoming

Indian Academy of Sciences (India)

2016-02-16

Feb 16, 2016 ... the permeability of multi-protein channel complexes. (receptors) .... ABCG2 overexpression is likely to be the cause of high- ... with low or absent function. ..... derivatives, is a water-soluble topoisomerase I inhibitor that.

Identification of intra- and intermolecular disulfide bridges in the multidrug resistance transporter ABCG2

DEFF Research Database (Denmark)

Henriksen, Ulla Birk; Fog, Jacob U; Litman, Thomas

2005-01-01

cysteines predicted to be on the extracellular face of ABCG2. Upon mutation of Cys-592 or Cys-608 to alanine (C592A and C608A), ABCG2 migrated as a dimer in SDS-PAGE under non-reducing conditions; however, mutation of Cys-603 to Ala (C603A) caused the transporter to migrate as a single monomeric band....... Despite this change, C603A displayed efficient membrane targeting and preserved transport function. Because the transporter migrated as a dimer in SDS-PAGE, when only Cys-603 was present (C592A-C608A), the data suggest that Cys-603 forms a symmetrical intermolecular disulfide bridge in the ABCG2 homodimer...

Dicty_cDB: Contig-U14921-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 498 e-139 AF399172_1( AF399172 |pid:none) Eutintinnus pectinis clone Epec99a... 497 e-139 AF399156_1( AF399...AF399175_1( AF399175 |pid:none) Eutintinnus pectinis clone Epec99a... 496 e-138 AF399137_1( AF399137 |pid:no

Double resonance spectroscopy of the D1Πu+ and B′′ B-bar 1Σu+ states near the third dissociation threshold of H2

International Nuclear Information System (INIS)

Ekey, R C; Cordova, A E; Duan, W; Chartrand, A M; McCormack, E F

2013-01-01

Double-resonance laser spectroscopy via the E,F 1 Σ g + ,v ′ =6,J ′ state was used to probe the energy region below the third dissociation limit of molecular hydrogen. Resonantly enhanced multi-photon ionization spectra were recorded by detecting ion production as a function of energy using a time-of-flight mass spectrometer. Energies and line widths for the v = 14–17 levels of the D 1 Π u + state of H 2 are reported and compared to experimental data obtained by using VUV synchrotron light excitation (Dickenson et al 2010 J. Chem. Phys. 133 144317) and fully ab initio non-adiabatic calculations of D 1 Π u + state energies and line widths (Glass-Maujean et al 2012 Phys. Rev. A 86 052507). Several high vibrational levels of the B ′′ B-bar 1 Σ u + state were also observed in this region. Term energies and rotational constants for the v = 67–69 vibrational levels are reported and compared to highly accurate ro-vibrational energy level predictions from fully ab initio non-adiabatic calculations of the first six 1 Σ u + levels of H 2 (Wolniewicz et al 2006 J. Mol. Spectrosc. 238 118). While additional observed transitions can be assigned to other states, several unassigned features in the spectra highlight the need for a fully integrated theoretical treatment of dissociation and ionization to understand the complex pattern of highly vibrationally excited states expected in this region. (paper)

The ABCG2 gene Q141K polymorphism contributes to an increased risk of gout: a meta-analysis of 2185 cases.

Science.gov (United States)

Qiu, Ya; Liu, Hua; Qing, Yufeng; Yang, Min; Tan, Xiaoyao; Zhao, Mingcai; Lin, Monica; Zhou, Jingguo

2014-09-01

Individual genetic association studies examining the relationship between the ABCG2 gene polymorphisms and gout have yielded inconsistent results. This study aims to evaluate the association between the ABCG2 gene variants and gout using meta-analysis. Relevant studies were identified by searching databases extensively. The odds ratio (OR) was calculated using a random-effect or fixed-effect model. A Q statistic was used to evaluate homogeneity, and Egger's test and funnel plot were used to assess publication bias. Subgroup analyses on ethnicities and sex were also performed. A total of 7 studies, including 2185 gout patients and 8028 controls from 5 countries or regions, were included and identified for the current meta-analysis. It was found that the A allele or AA genotype of the ABCG2 Q141K polymorphism (rs2231142) had an increased risk of gout in the general population (A allele, p gout (p gout.

A gene-wide investigation on polymorphisms in the ABCG2/BRCP transporter and susceptibility to colorectal cancer

Czech Academy of Sciences Publication Activity Database

Campa, D.; Pardini, Barbara; Naccarati, Alessio; Vodičková, Ludmila; Novotný, J.; Försti, A.; Hemminki, K.; Barale, R.; Vodička, Pavel; Canzian, F.

2008-01-01

Roč. 645, 1-2 (2008), s. 56-60 ISSN 0027-5107 R&D Projects: GA ČR GA310/07/1430 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50390703 Keywords : ABCG2 * Transporter * Colorectal cancer Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.198, year: 2008

Celecoxib sensitizes imatinib-resistant K562 cells to imatinib by inhibiting MRP1-5, ABCA2 and ABCG2 transporters via Wnt and Ras signaling pathways.

Science.gov (United States)

Dharmapuri, Gangappa; Doneti, Ravinder; Philip, Gundala Harold; Kalle, Arunasree M

2015-07-01

Imatinib mesylate, a tyrosine kinase inhibitor, is very effective in the treatment of chronic myeloid leukemia (CML). However, development of resistance to imatinib therapy is also a very common mechanism observed with long-term administration of the drug. Our previous studies have highlighted the role of cyclooxygenase-2 (COX-2) in regulating the expression of multidrug resistant protein-1 (MDR1), P-gp, in imatinib-resistant K562 cells (IR-K562) via PGE2-cAMP-PKC-NF-κB pathway and inhibition of COX-2 by celecoxib, a COX-2 specific inhibitor, inhibits this pathway and reverses the drug resistance. Studies have identified that not only MDR1 but other ATP-binding cassette transport proteins (ABC transporters) are involved in the development of imatinib resistance. Here, we tried to study the role of COX-2 in the regulation of other ABC transporters such as MRP1, MRP2, MRP3, ABCA2 and ABCG2 that have been already implicated in imatinib resistance development. The results of the study clearly indicated that overexpression of COX-2 lead to upregulation of MRP family proteins in IR-K562 cells and celecoxib down-regulated the ABC transporters through Wnt and MEK signaling pathways. The study signifies that celecoxib in combination with the imatinib can be a good alternate treatment strategy for the reversal of imatinib resistance. Copyright © 2015 Elsevier Ltd. All rights reserved.

THE BEATLES 2.1

DEFF Research Database (Denmark)

Nielsen, Steen Kaargaard

2010-01-01

Blog-essay publiceret på følgende web-adresse: www.avlyt.dk/2010/04/the-beatles-2-1-om-emis-forvaltning-af-the-fab-fours-lydværk-og-værklyd......Blog-essay publiceret på følgende web-adresse: www.avlyt.dk/2010/04/the-beatles-2-1-om-emis-forvaltning-af-the-fab-fours-lydværk-og-værklyd...

Dicty_cDB: Contig-U03971-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 52 2e-05 FJ771006_1( FJ771006 |pid:none) HIV-1 isolate 02BR082 from Brazil,... 52 2e-05 AY352275_1( AY35227...Y727522_1( AY727522 |pid:none) HIV-1 isolate 04BR013 from Brazil ... 51 3e-05 AF516184_1( AF516184 |pid:none...pid:none) HIV-1 isolate 110PA from Brazil, c... 50 4e-05 DQ792987_1( DQ792987 |pi

Rev1 Recruits Ung to Switch Regions and Enhances dU Glycosylation for Immunoglobulin Class Switch DNA Recombination

Directory of Open Access Journals (Sweden)

Hong Zan

2012-11-01

Full Text Available By diversifying the biological effector functions of antibodies, class switch DNA recombination (CSR plays a critical role in the maturation of the immune response. It is initiated by activation-induced cytidine deaminase (AID-mediated deoxycytosine deamination, yielding deoxyuridine (dU, and dU glycosylation by uracil DNA glycosylase (Ung in antibody switch (S region DNA. Here we showed that the translesion DNA synthesis polymerase Rev1 directly interacted with Ung and targeted in an AID-dependent and Ung-independent fashion the S regions undergoing CSR. Rev1−/− Ung+/+ B cells reduced Ung recruitment to S regions, DNA-dU glycosylation, and CSR. Together with an S region spectrum of mutations similar to that of Rev1+/+ Ung−/− B cells, this suggests that Rev1 operates in the same pathway as Ung, as emphasized by further decreased CSR in Rev1−/− Msh2−/− B cells. Rescue of CSR in Rev1−/− B cells by a catalytically inactive Rev1 mutant shows that the important role of Rev1 in CSR is mediated by Rev1’s scaffolding function, not its enzymatic function.

Transmembrane Domain Single-Nucleotide Polymorphisms Impair Expression and Transport Activity of ABC Transporter ABCG2

NARCIS (Netherlands)

Sjostedt, N.; Heuvel, J.J.M.W. van den; Koenderink, J.B.; Kidron, H.

2017-01-01

PURPOSE: To study the function and expression of nine naturally occurring single-nucleotide polymorphisms (G406R, F431L, S441N, P480L, F489L, M515R, L525R, A528T and T542A) that are predicted to reside in the transmembrane regions of the ABC transporter ABCG2. METHODS: The transport activity of the

Registrering og Benchmarking af Modus 2 Forskning

DEFF Research Database (Denmark)

Duus, Henrik Johannsen; Jørgensen, Jens E.

2004-01-01

Fremvæksten af modus 2 forskning stiller krav om en revurdering af højere læreanstalters evaluerings- og meriteringspraksis. Den endimensionale prioritering af modus 1 forskning såvel som dennes ligeså endimensionale evaluering via publikationer må afvises som utidssvarende. Som en konsekvens her...

Structural diversity and evolution of the N-terminal isoform-specific region of ecdysone receptor-A and -B1 isoforms in insects

Directory of Open Access Journals (Sweden)

Kubo Takeo

2010-02-01

Full Text Available Abstract Background The ecdysone receptor (EcR regulates various cellular responses to ecdysteroids during insect development. Insects have multiple EcR isoforms with different N-terminal A/B domains that contain the isoform-specific activation function (AF-1 region. Although distinct physiologic functions of the EcR isoforms have been characterized in higher holometabolous insects, they remain unclear in basal direct-developing insects, in which only A isoform has been identified. To examine the structural basis of the EcR isoform-specific AF-1 regions, we performed a comprehensive structural comparison of the isoform-specific region of the EcR-A and -B1 isoforms in insects. Results The EcR isoforms were newly identified in 51 species of insects and non-insect arthropods, including direct-developing ametabolous and hemimetabolous insects. The comprehensive structural comparison revealed that the isoform-specific region of each EcR isoform contained evolutionally conserved microdomain structures and insect subgroup-specific structural modifications. The A isoform-specific region generally contained four conserved microdomains, including the SUMOylation motif and the nuclear localization signal, whereas the B1 isoform-specific region contained three conserved microdomains, including an acidic activator domain-like motif. In addition, the EcR-B1 isoform of holometabolous insects had a novel microdomain at the N-terminal end. Conclusions Given that the nuclear receptor AF-1 is involved in cofactor recruitment and transcriptional regulation, the microdomain structures identified in the isoform-specific A/B domains might function as signature motifs and/or as targets for cofactor proteins that play essential roles in the EcR isoform-specific AF-1 regions. Moreover, the novel microdomain in the isoform-specific region of the holometabolous insect EcR-B1 isoform suggests that the holometabolous insect EcR-B1 acquired additional transcriptional

Duality invariance of non-anticommutative N = 1/2 supersymmetric U(1) gauge theory

International Nuclear Information System (INIS)

Dayi, Oemer F.; Kelleyane, Lara T.; Uelker, Kayhan

2005-01-01

A parent action is introduced to formulate (S-) dual of non-anticommutative N = 1/2 supersymmetric U(1) gauge theory. Partition function for parent action in phase space is utilized to establish the equivalence of partition functions of the theories which this parent action produces. Thus, duality invariance of non-anticommutative N = 1/2 supersymmetric U(1) gauge theory follows. The results which we obtained are valid at tree level or equivalently at the first order in the nonanticommutativity parameter C μν

Dicty_cDB: Contig-U01385-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available DRAF... 46 2.0 1 ( EJ296094 ) 1095388038537 Global-Ocean-Sampling_GS-27-01-01-1... 46 2.0 1 ( CB895163 ) EST647955 HOGA Med...067741 |pid:none) Homo sapiens proteasome (prosome, ... 35 2.7 AF323913_1( AF323913 |pid:none) Neurospora crassa interm...094293 ) 1092962025663 Global-Ocean-Sampling_GS-31-01-01-1... 36 1.4 2 ( CU570868 ) M.truncatula DNA sequenc...:none) Leishmania major strain Friedlin... 37 0.94 CP001213_467( CP001213 |pid:none) Bifidobacterium animali...icago truncatula clone mth2-165c4, complete se... 46 2.0 1 ( AC150776 ) Medicago truncatula c

ABCG2/BCRP decreases the transfer of a food-born chemical carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in perfused term human placenta

International Nuclear Information System (INIS)

Myllynen, Paeivi; Kummu, Maria; Kangas, Tiina; Ilves, Mika; Immonen, Elina; Rysae, Jaana; Pirilae, Rauna; Lastumaeki, Anni; Vaehaekangas, Kirsi H.

2008-01-01

We have studied the role of ATP binding cassette (ABC) transporters in fetal exposure to carcinogens using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) a known substrate for ABC transporters as a model compound. In perfusion of human term placenta, transfer of 14 C-PhIP (2 μM) through the placenta resulted in fetal-to-maternal concentration ratio (FM ratio) of 0.72 ± 0.09 at 6 h. The specific ABCG2 inhibitor KO143 increased the transfer of 14 C-PhIP from maternal to fetal circulation (FM ratio 0.90 ± 0.08 at 6 h, p 14 C-PhIP (R = - 0.81, p 14 C-PhIP in perfused human placenta. Also, PhIP may modify ABC transporter expression in choriocarinoma cells

Dicty_cDB: Contig-U08887-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 1 FN317772_1( FN317772 |pid:none) Schistosoma japonicum isolate Anhu... 72 6e-11 X98769_1( X98769 |pid:none) Megaselia scala...ris mRNA for Sex-lethal... 71 1e-10 AJ000546_1( AJ000546 |pid:none) Megaselia scala...a cruzi RNA-binding prot... 67 2e-09 AF110846_1( AF110846 |pid:none) Megaselia scalaris sex-lethal homo... 6

Hvornår har 1.000 landbrug 90 pct. af landbrugsjorden?

DEFF Research Database (Denmark)

Hansen, Henning Otte

2017-01-01

relativt lige i forhold til resten af EU. De 1.000 største landbrug driver ca. 22 pct. af landbrugsjorden, og andelen er stigende. Selv om strukturudviklingen ser ud til at fortsætte upåvirket af de økonomiske og markedsmæssige forhold, kan man identificere en række forhold, som er drivkræfter bag...... strukturudviklingen. De senere års liberalisering af landbrugsloven har sandsynligvis været med til fremme strukturudviklingen yderligere, og også fjernelsen af EU‘s mælkekvoter ser ud til at have genskabt den hidtidige udvikling. Om strukturudviklingen er en fordel eller en ulempe kan ikke afgøres entydigt, idet...

Dicty_cDB: Contig-U05006-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available AE017355_2391( AE017355 |pid:none) Bacillus thuringiensis serovar ... 33 3.8 DQ194420_1( DQ194420 |pid:none) Maori...ne) Kikihia sp. 'aotea east' cytochrom... 33 6.6 AF313507_1( AF313507 |pid:none) Maoricicada cassiope cytoch...toc... 33 6.6 DQ194397_1( DQ194397 |pid:none) Maoricicada nigra nigra voucher M.... 33 6.6 AF205156_1( AF205...otermes brevis voucher BYU IG... 33 6.6 DQ194417_1( DQ194417 |pid:none) Maoricicada oromelaena voucher M.o..... 6.6 DQ194392_1( DQ194392 |pid:none) Maoricicada otagoensis maceweni vo... 33 6.6 AF205144_1( AF205144 |pid:

Dicty_cDB: Contig-U08145-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available . 50 1e-04 AF021822_1( AF021822 |pid:none) Scaptodrosophila lebanonensis supe... ...emonia viridis copper/zinc super... 49 6e-04 AF021824_1( AF021824 |pid:none) Hirtodrosophila pictiventris su

Regional alternative transportation evaluation report - region 1

Science.gov (United States)

2011-01-21

The U.S. Fish and Wildlife Service (FWS) and the U.S. Department of Transportation (DOT) Volpe Center (Volpe Center) conducted a regional alternative transportation evaluation (RATE) in Region 1, which is comprised of Oregon, Idaho, Washington, and H...

Antibody validation and scoring guidelines for ABCG2 immunohistochemical staining in formalin-fixed paraffin-embedded colon cancer tissue

DEFF Research Database (Denmark)

Cederbye, Camilla Natasha; Palshof, Jesper Andreas; Hansen, Tine Plato

2016-01-01

cancer (CRC), probably because of the use of different antibodies and scoring approaches. In this study, we systematically studied six commercially available anti-ABCG2 antibodies, using cell lines with up-regulation of ABCG2, and selected one antibody for validation in CRC tissue. Furthermore, we...... sections, especially when more than one core was used. In conclusion, here, we provide validated results to guide future studies on the associations between ABCG2 immunoreactivity in tumor cells and the benefits of chemotherapeutic treatment in patients with CRC...

IND-2, a pyrimido[1″,2″:1,5]pyrazolo[3,4-b]quinoline derivative, circumvents multi-drug resistance and causes apoptosis in colon cancer cells.

Science.gov (United States)

Karthikeyan, Chandrabose; Lee, Crystal; Moore, Joshua; Mittal, Roopali; Suswam, Esther A; Abbott, Kodye L; Pondugula, Satyanarayana R; Manne, Upender; Narayanan, Narayanan K; Trivedi, Piyush; Tiwari, Amit K

2015-02-01

Naturally occurring condensed quinolines have anticancer properties. In efforts to find active analogues, we designed and synthesized eight polycyclic heterocycles with a pyrimido[1″,2″:1,5]pyrazolo[3,4-b]quinoline framework (IND series). The compounds were evaluated for activity against colon (HCT-116 and S1-MI-80), prostate (PC3 and DU-145), breast (MCF-7 and MDAMB-231), ovarian (ov2008 and A2780), and hepatocellular (HepG2) cancer cells and against non-cancerous Madin Darby canine kidney (MDCK), mouse embryonic fibroblast (NIH/3T3), and human embryonic kidney cells (HEK293). IND-2, a 4-chloro-2-methyl pyrimido[1″,2″:1,5]pyrazolo[3,4-b]quinoline, exhibited more than ten-fold selectivity and potent cytotoxic activity against colon cancer cells relative to the other cancer and non-cancer cells. With five additional colon cancer cell lines (HT-29, HCT-15, LS-180, LS-174, and LoVo), IND-2 had similar cytotoxicity and selectivity, and sub-micromolar concentrations caused changes in the morphology of HCT-116 and HCT-15 cells. IND-2 did not activate the transactivating function of the pregnane X receptor (PXR), indicating that it does not induce PXR-regulated ABCB1 or ABCG2 transporters. Indeed, IND-2 was not a substrate of ABCB1 or ABCG2, and it induced cytotoxicity in HEK293 cells overexpressing ABCB1 or ABCG2 to the same extent as in normal HEK293 cells. IND-2 was cytotoxic to resistant colon carcinoma S1-MI-80 cells, approximately three- and five-fold more than SN-38 and topotecan, respectively. In HCT-116 colon cancer cells, IND-2 produced concentration-dependent changes in mitochondrial membrane potential, leading to apoptosis, and sub-micromolar concentrations caused chromosomal DNA fragmentation. These findings suggest that, by increasing apoptosis, IND-2 has potential therapeutic efficacy for colorectal cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

VG2 URA TRAJECTORY DERIVED SUMM U1 COORDS 48SEC V1.0

Data.gov (United States)

National Aeronautics and Space Administration — This dataset contains Voyager 2 spacecraft position vectors relative to Uranus in minus U1 coordinates. The U1 or Uranus West Longitude System coordinate system is a...

Dicty_cDB: Contig-U06984-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available tigen NY-CO-7 (NY-C... 36 0.56 AF129085_1( AF129085 |pid:none) Homo sapiens carboxy terminus of H... 36 0.56... DNA Entam... 44 5.1 1 ( EK423693 ) 1095515647805 Global-Ocean-Sampling_GS-31-01-...2962047198 Global-Ocean-Sampling_GS-31-01-01-1... 34 8.3 2 ( AC117108 ) Rattus norvegicus clone CH230-240I5,...SEQUENC... 30 8.6 2 ( EK533234 ) 1095516016996 Global-Ocean-Sampling_GS-32-01-01-1... 40 8.9 2 ( AC106212 ) ...Rattus norvegicus clone CH230-42I19, *** SEQUENCI... 30 9.0 2 ( ER390099 ) 1094428835918 Global-Ocean-Sampli

Dicty_cDB: Contig-U15623-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available F079138_3( AF079138 |pid:none) Streptomyces venezuelae methymycin... 32 0.026 CT573213_2489( CT573213 |pid:n...) Streptomyces griseus subsp. gris... 44 0.030 AF015823_1( AF015823 |pid:none) Streptomyces venezuelae venA ...d:none) Leptosphaeria maculans HDX1 (HDX1)... 36 0.058 AF079138_6( AF079138 |pid:none) Streptomyces venezuela

Dicty_cDB: Contig-U13747-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Simonyella variegata isolate AFTOL... 146 5e-34 DQ986817_1( DQ986817 |pid:none) Lecanora...chinus voucher TSJ... 141 1e-32 DQ782829_1( DQ782829 |pid:none) Lecanora hybocarpa isolate AFTOL-I... 141 1e...DQ447888_1( DQ447888 |pid:none) Cheimonophyllum candidissimum isol... 140 3e-32 EF105431_1( EF105431 |pid:none) Lecanora...2_1( EF105432 |pid:none) Lecanora sulphurea RNA polymerase ... 136 6e-31 AF389538_1( AF389538 |pid:none) Ino

Multixenobiotic resistance in Mytilus edulis: Molecular and functional characterization of an ABCG2- type transporter in hemocytes and gills.

Science.gov (United States)

Ben Cheikh, Yosra; Xuereb, Benoit; Boulangé-Lecomte, Céline; Le Foll, Frank

2018-02-01

Among the cellular protection arsenal, ABC transporters play an important role in xenobiotic efflux in marine organisms. Two pumps belonging to B and C subfamily has been identified in Mytilus edulis. In this study, we investigated the presence of the third major subtype ABCG2/BCRP protein in mussel tissues. Transcript was expressed in hemocytes and with higher level in gills. Molecular characterization revealed that mussel ABCG2 transporter shares the sequence and organizational structure with mammalian and molluscan orthologs. Overall identity of the predicted amino acid sequence with corresponding homologs from other organisms was between 49% and 98%. Moreover, protein efflux activity was demonstrated using a combination of fluorescent allocrites and specific inhibitors. The accumulation of bodipy prazosin and pheophorbide A was heterogeneous in gills and hemocytes. Most of the used blockers enhanced probe accumulation at different levels, most significantly for bodipy prazosin. Moreover, Mrp classical blocker MK571 showed a polyspecificity. In conclusion, our data demonstrate that several ABC transporters contribute to MXR phenotype in the blue mussel including ABCG2 that forms an active pump in hemocytes and gills. Efforts are needed to distinguish between the different members and to explore their single function and specificity towards allocrites and chemosensitizers. Copyright © 2017 Elsevier B.V. All rights reserved.

Dicty_cDB: Contig-U06400-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available . pom... 36 0.72 AF489463_2( AF489463 |pid:none) Orussus terminalis NADH dehydrogen... 36 0.94 CP001229_564(...K566108 ) 1095521042507 Global-Ocean-Sampling_GS-32-01-01-1... 34 1.0 2 ( CU469464 ) Candidatus Phytopl...tus clone R3-3117D16, W... 46 1.4 1 ( EJ362356 ) 1092963691825 Global-Ocean-Sampling_GS-28-01-01-1... 46 1.4...SE... 44 5.7 1 ( EK340302 ) 1095467059309 Global-Ocean-Sampling_GS-31-01-01-1... 44 5.7 1 ( EK314173 ) 10954...62407059 Global-Ocean-Sampling_GS-31-01-01-1... 44 5.7 1 ( EK262899 ) 1095462187822 Global-Ocean-Sampling_GS

Dicty_cDB: Contig-U08834-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available .. 40 0.012 11 ( AM422018 ) Candidatus Phytoplasma australiense complete genome. 36 0.012 19 ( AC005308 ) Pl...tig VV78X172452.29, whole genom... 42 0.081 3 ( FL645023 ) TS46-F4 Reticulitermes flavipes symbiont library ...AF053733 |pid:none) Expression vector pPK113, complete... 206 2e-51 T51932( T51932 ) kinesin [imported...*** f... 38 0.018 6 ( ER570718 ) 1093015791013 Global-Ocean-Sampling_GS-36-01-01-2... 46 0.018 3 ( DY888602 ...ulans strain w501 ki... 189 1e-46 AF319546_1( AF319546 |pid:none) Trypanosoma brucei C-term

PDK2 and ABCG2 genes polymorphisms are correlated with blood glucose levels and uric acid in Tibetan gout patients.

Science.gov (United States)

Ren, Y C; Jin, T B; Sun, X D; Geng, T T; Zhang, M X; Wang, L; Feng, T; Kang, L L; Chen, C

2016-02-11

Previous studies have shown that the PDK2 and ABCG2 genes play important roles in many aspects of gout development in European populations. However, a detailed genotype-phenotype analysis was not performed. The aim of the present study was to investigate the potential association between variants in these two genes and metabolism-related quantitative phenotypes relevant to gout in a Chinese Tibetan population. In total, 316 Chinese Tibetan gout patients were recruited from rheumatology outpatient clinics and 6 single nucleotide polymorphisms in PDK2 and ABCG2 were genotyped, which were possible etiologic variants as identified in the HapMap Chinese Han Beijing population. A significant difference in blood glucose levels was detected between different genotypes of rs2728109 (P = 0.005) in the PDK2 gene. We also detected a significant difference in the mean serum uric levels between different genotypes of rs3114018 (P = 0.004) in the ABCG2 gene. All P values remained significant after Bonferroni's correction for multiple testing. Our data demonstrate potential roles for PDK2 and ABCG2 polymorphisms in the metabolic phenotypes of Tibetan gout patients, which may provide new insights into the etiology of gout. Further studies are required to confirm these findings.

Purification and biochemical characterization of NpABCG5/NpPDR5, a plant pleiotropic drug resistance transporter expressed in Nicotiana tabacum BY-2 suspension cells.

Science.gov (United States)

Toussaint, Frédéric; Pierman, Baptiste; Bertin, Aurélie; Lévy, Daniel; Boutry, Marc

2017-05-04

Pleiotropic drug resistance (PDR) transporters belong to the ABCG subfamily of ATP-binding cassette (ABC) transporters and are involved in the transport of various molecules across plasma membranes. During evolution, PDR genes appeared independently in fungi and in plants from a duplication of a half-size ABC gene. The enzymatic properties of purified PDR transporters from yeast have been characterized. This is not the case for any plant PDR transporter, or, incidentally, for any purified plant ABC transporter. Yet, plant PDR transporters play important roles in plant physiology such as hormone signaling or resistance to pathogens or herbivores. Here, we describe the expression, purification, enzymatic characterization and 2D analysis by electron microscopy of NpABCG5/NpPDR5 from Nicotiana plumbaginifolia , which has been shown to be involved in the plant defense against herbivores. We constitutively expressed NpABCG5/NpPDR5, provided with a His-tag in a homologous system: suspension cells from Nicotiana tabacum (Bright Yellow 2 line). NpABCG5/NpPDR5 was targeted to the plasma membrane and was solubilized by dodecyl maltoside and purified by Ni-affinity chromatography. The ATP-hydrolyzing specific activity (27 nmol min -1  mg -1 ) was stimulated seven-fold in the presence of 0.1% asolectin. Electron microscopy analysis indicated that NpABCG5/NpPDR5 is monomeric and with dimensions shorter than those of known ABC transporters. Enzymatic data (optimal pH and sensitivity to inhibitors) confirmed that plant and fungal PDR transporters have different properties. These data also show that N. tabacum suspension cells are a convenient host for the purification and biochemical characterization of ABC transporters. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Interaction of the EGFR inhibitors gefitinib, vandetanib, pelitinib and neratinib with the ABCG2 multidrug transporter: implications for the emergence and reversal of cancer drug resistance.

Science.gov (United States)

Hegedüs, Csilla; Truta-Feles, Krisztina; Antalffy, Géza; Várady, György; Német, Katalin; Ozvegy-Laczka, Csilla; Kéri, György; Orfi, László; Szakács, Gergely; Settleman, Jeffrey; Váradi, András; Sarkadi, Balázs

2012-08-01

Human ABCG2 is a plasma membrane glycoprotein that provides physiological protection against xenobiotics. ABCG2 also significantly influences biodistribution of drugs through pharmacological tissue barriers and confers multidrug resistance to cancer cells. Moreover, ABCG2 is the molecular determinant of the side population that is characteristically enriched in normal and cancer stem cells. Numerous tumors depend on unregulated EGFR signaling, thus inhibition of this receptor by small molecular weight inhibitors such as gefitinib, and the novel second generation agents vandetanib, pelitinib and neratinib, is a promising therapeutic option. In the present study, we provide detailed biochemical characterization regarding the interaction of these EGFR inhibitors with ABCG2. We show that ABCG2 confers resistance to gefitinib and pelitinib, whereas the intracellular action of vandetanib and neratinib is unaltered by the presence of the transporter. At higher concentrations, however, all these EGFR inhibitors inhibit ABCG2 function, thereby promoting accumulation of ABCG2 substrate drugs. We also report enhanced expression of ABCG2 in gefitinib-resistant non-small cell lung cancer cells, suggesting potential clinical relevance of ABCG2 in acquired drug resistance. Since ABCG2 has important impact on both the pharmacological properties and anti-cancer efficiencies of drugs, our results regarding the novel EGFR inhibitors should provide useful information about their therapeutic applicability against ABCG2-expressing cancer cells depending on EGFR signaling. In addition, the finding that these EGFR inhibitors efficiently block ABCG2 function may help to design novel drug-combination therapeutic strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

Dicty_cDB: Contig-U12284-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available nogaster LD14594 fu... 185 3e-45 AF107797_1( AF107797 |pid:none) Capronia mansonii DNA-dependent RN... 185 3...1( AF107798 |pid:none) Capronia pilosella DNA-dependent R... 120 9e-26 AJ634168_1( AJ634168 |pid:none) Silen..._1( AY699223 |pid:none) Musa velutina RNA polymerase II se... 120 9e-26 AF107798_

Photoassociation spectroscopy of 87Rb2 (5s1/2+5p1/2)0u+ long-range molecular states: Coupling with the (5s1/2+5p3/2)0u+ series analyzed using the Lu-Fano approach

International Nuclear Information System (INIS)

Jelassi, H.; Viaris de Lesegno, B.; Pruvost, L.

2006-01-01

We report on photoassociation of cold 87 Rb atoms providing the spectroscopy of (5s 1/2 +5p 1/2 )0 u + long-range molecular states, in the energy range of [-12.5, -0.7 cm -1 ] below the dissociation limit. A Lu-Fano approach coupled to the LeRoy-Bernstein formula is used to analyze the data. The Lu-Fano graph exhibits the coupling of the molecular series with the (5s 1/2 +5p 3/2 )0 u + one, which is due to spin effects in the molecule. A two-channel model involving an improved LeRoy-Bernstein formula allows us to characterize the molecular series, to localize (5s 1/2 +5p 3/2 )0 u + levels, to evaluate the coupling, and to predict the energy and width of the first predissociated level of (5s 1/2 +5p 3/2 )0 u + series. An experimental spectrum confirms the prediction

Dicty_cDB: Contig-U14443-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 314998_1( AK314998 |pid:none) Homo sapiens cDNA, FLJ95925, highl... 36 3.6 AY092033_1( AY092033 |pid:none) Homo sapiens NALP3 interm... EK187609 ) 1095460006975 Global-Ocean-Sampling_GS-31-01-01-1... 36 2.5 3 ( AC168354 ) Strongylocentrotus pu... 9 ( EJ184534 ) 1092344144110 Global-Ocean-Sampling_GS-27-01-01-1... 34 2.6 3 ( BX571898 ) Zebrafish DNA seq... |pid:none) Leishmania major strain Friedlin,... 57 2e-06 AM494972_448( AM494972 |pid:none) Leishmania brazilie...1( AK304700 |pid:none) Homo sapiens cDNA FLJ54257 complet... 47 0.002 AF165215_1( AF165215 |pid:none) Gallus gallus Sk-tropomoduli

Dicty_cDB: Contig-U15121-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 242194_1( AF242194 |pid:none) Drosophila melanogaster brakeless-... 37 0.78 AE014298_2663( AE014298 |pid:non...an pneumovirus strain Mn-1a att... 37 1.0 AF238858_1( AF238858 |pid:none) Drosophila melanogaster brakeless

Dicty_cDB: Contig-U04495-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Full=Seryl-tRNA synthetase; EC=6.1.1.... 38 0.097 AF101063_1( AF101063 |pid:none) Hirudo medicinalis intermed...9 |pid:none) Haemopis marmorata neuronal intermedia... 40 0.033 (Q2JXL1) RecName:..... 36 5.2 3 ( AC222582 ) Bos taurus clone CH240-445A18, WORKING DRAFT SEQU... 38 5.5 3 ( EJ360574 ) 1092963685063 Global-Ocean-Sampli...eptomyces natalensis Pho regulo... 32 6.9 AJ575294_1( AJ575294 |pid:none) Ciona intestinali...a gladiata maturase K (matK) gene, compl... 48 0.28 1 ( AY034204 ) Wolffiella oblonga maturase K (matK) gene, compl

Detailed CO(J = 1-0, 2-1, and 3-2) observations toward an H II region RCW 32 in the Vela Molecular Ridge

Science.gov (United States)

Enokiya, Rei; Sano, Hidetoshi; Hayashi, Katsuhiro; Tachihara, Kengo; Torii, Kazufumi; Yamamoto, Hiroaki; Hattori, Yusuke; Hasegawa, Yutaka; Ohama, Akio; Kimura, Kimihiro; Ogawa, Hideo; Fukui, Yasuo

2018-05-01

We performed CO(J = 1-0, 2-1, and 3-2) observations toward an H II region RCW 32 in the Vela Molecular Ridge. The CO gas distribution associated with the H II region was revealed for the first time at a high resolution of 22″. The results revealed three distinct velocity components which show correspondence with the optical dark lanes and/or Hα distribution. Two of the components show complementary spatial distribution which suggests collisional interaction between them at a relative velocity of ˜ 4 km s-1. Based on these results, we present a hypothesis that a cloud-cloud collision determined the cloud distribution and triggered formation of the exciting star ionizing RCW 32. The collision time scale is estimated from the cloud size and the velocity separation to be ˜2 Myr and the collision terminated ˜1 Myr ago, which is consistent with the age of the exciting star and the associated cluster. By combing the previous works on the H II regions in the Vela Molecular Ridge, we argue that the majority (at least four) of the H II regions in the Ridge were formed by triggering of cloud-cloud collision.

Dicty_cDB: Contig-U12111-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available ces producing significant alignments: (bits) Value AF096896_1( AF096896 |pid:none) Drosophila melanogaster pushove... CR318658 |pid:none) Zebrafish DNA sequence from clone ... 34 7.9 >AF096896_1( AF096896 |pid:none) Drosophila melanogaster pushove

SLC22A1-ABCB1 haplotype profiles predict imatinib pharmacokinetics in Asian patients with chronic myeloid leukemia.

Directory of Open Access Journals (Sweden)

Onkar Singh

Full Text Available OBJECTIVE: This study aimed to explore the influence of SLC22A1, PXR, ABCG2, ABCB1 and CYP3A5 3 genetic polymorphisms on imatinib mesylate (IM pharmacokinetics in Asian patients with chronic myeloid leukemia (CML. PATIENTS AND METHODS: Healthy subjects belonging to three Asian populations (Chinese, Malay, Indian; n = 70 each and CML patients (n = 38 were enrolled in a prospective pharmacogenetics study. Imatinib trough (C(0h and clearance (CL were determined in the patients at steady state. Haplowalk method was applied to infer the haplotypes and generalized linear model (GLM to estimate haplotypic effects on IM pharmacokinetics. Association of haplotype copy numbers with IM pharmacokinetics was defined by Mann-Whitney U test. RESULTS: Global haplotype score statistics revealed a SLC22A1 sub-haplotypic region encompassing three polymorphisms (rs3798168, rs628031 and IVS7+850C>T, to be significantly associated with IM clearance (p = 0.013. Haplotype-specific GLM estimated that the haplotypes AGT and CGC were both associated with 22% decrease in clearance compared to CAC [CL (10(-2 L/hr/mg: CAC vs AGT: 4.03 vs 3.16, p = 0.017; CAC vs CGC: 4.03 vs 3.15, p = 0.017]. Patients harboring 2 copies of AGT or CGC haplotypes had 33.4% lower clearance and 50% higher C(0h than patients carrying 0 or 1 copy [CL (10(-2 L/hr/mg: 2.19 vs 3.29, p = 0.026; C(0h (10(-6 1/ml: 4.76 vs 3.17, p = 0.013, respectively]. Further subgroup analysis revealed SLC22A1 and ABCB1 haplotypic combinations to be significantly associated with clearance and C(0h (p = 0.002 and 0.009, respectively. CONCLUSION: This exploratory study suggests that SLC22A1-ABCB1 haplotypes may influence IM pharmacokinetics in Asian CML patients.

Symmetry breaking of u(6/2j+1) supersymmetric models

International Nuclear Information System (INIS)

Baake, M.; Reinicke, P.

1985-09-01

In this paper, we present the group theory of models with broken u(6/2j+1) supersymmetry described by the chain u(6/2j+1) contains usub(B)(6) x usub(F)(2j+1) contains usub(B)(6) x spsub(F)(2j+1) contains ... contains sosub(B)(3) x susub(F)(2) contains susub(B+F)(2) which has recently been suggested for application to nuclear physics. We present all invariants that are needed for the construction of the general Hamiltonian for this model. (orig.)

U (1 ) -symmetric infinite projected entangled-pair states study of the spin-1/2 square J1-J2 Heisenberg model

Science.gov (United States)

Haghshenas, R.; Sheng, D. N.

2018-05-01

We develop an improved variant of U (1 ) -symmetric infinite projected entangled-pair states (iPEPS) ansatz to investigate the ground-state phase diagram of the spin-1 /2 square J1-J2 Heisenberg model. In order to improve the accuracy of the ansatz, we discuss a simple strategy to select automatically relevant symmetric sectors and also introduce an optimization method to treat second-neighbor interactions more efficiently. We show that variational ground-state energies of the model obtained by the U (1 ) -symmetric iPEPS ansatz (for a fixed bond dimension D ) set a better upper bound, improving previous tensor-network-based results. By studying the finite-D scaling of the magnetically order parameter, we find a Néel phase for J2/J1place at J2c2/J1=0.610 (2 ) to the conventional Stripe phase. We compare our results with earlier DMRG and PEPS studies and suggest future directions for resolving remaining issues.

Dicty_cDB: Contig-U12991-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available ( AF272150 ) Dictyostelium discoideum deliriumA (dlrA) gene, c... 2022 0.0 3 ( BJ...39594 ) TT1EP48TV Tetrahymena thermophila SB210 cDNA libr... 38 10.0 2 >( AF272150 ) Dictyostelium discoideum delirium

Spectroscopic constants and potential energy curve of the iodine weakly bound 1u state correlating with the I(2P1/2) + I(2P1/2) dissociation limit

International Nuclear Information System (INIS)

Akopyan, M E; Baturo, V V; Lukashov, S S; Poretsky, S A; Pravilov, A M

2015-01-01

The stepwise three-step three-color laser population of the I 2 (β1 g , ν β , J β ) rovibronic states via the B0 u + , ν B , J B rovibronic states and rovibronic levels of the 1 u (bb) and 0 g + (bb) states mixed by hyperfine interaction is used for determination of rovibronic level energies of the weakly bound I 2 (1 u (bb)) state. Dunham coefficients of the state, Y i0 (i = 0–3), Y i1 (i = 0–2), Y 02 and Y 12 for the v 1 u  = 1–5, 8, 10, 15 and J 1 u  ≈ 9–87 ranges, the dissociation energy of the state, D e , and equilibrium I–I distance, R e , as well as the potential energy curve are determined. There are aperiodicities in the excitation spectrum corresponding to the β, ν β  = 23, J β  ← 1 u (bb), ν 1u  = 4, 5, J 1u progressions in the I 2  + Rg = He, Ar mixture, namely, a great number of lines which do not coincide with the R or P line progressions. Their positions conflict with the ΔJ-even selection rule. Furthermore, they do not correspond to the ΔJ-odd progression. (paper)

Short communication: The gain-of-function Y581S polymorphism of the ABCG2 transporter increases secretion into milk of danofloxacin at the therapeutic dose for mastitis treatment.

Science.gov (United States)

Otero, J A; Barrera, B; de la Fuente, A; Prieto, J G; Marqués, M; Álvarez, A I; Merino, G

2015-01-01

The ATP-binding cassette transporter ABCG2 restricts the exposure of certain drugs and natural compounds in different tissues and organs. Its expression in the mammary gland is induced during lactation and is responsible for the active secretion of many compounds into milk, including antimicrobial agents. This particular function of ABCG2 may affect drug efficacy against mastitis and the potential presence of drug residues in the milk. Previous in vitro and in vivo studies showed increased transport of several compounds, including fluoroquinolones, by the bovine ABCG2 Y581S polymorphism. Our main purpose was to study the potential effect of this bovine ABCG2 polymorphism on the secretion into milk of the antimicrobial danofloxacin administered at the therapeutic dose of 6mg/kg used for mastitis treatment. In addition, the effect of this polymorphism on the relative mRNA and protein levels of ABCG2 by quantitative real-time PCR and Western blot were studied. Danofloxacin 18% (6mg/kg) was administered to 6 Y/Y homozygous and 5 Y/S heterozygous cows. Danofloxacin levels in milk and milk-to-plasma concentration ratios were almost 1.5- and 2-fold higher, respectively, in Y/S cows compared with the Y/Y cows, showing a higher capacity of this variant to transport danofloxacin into milk. Furthermore, the higher activity of this polymorphism is not linked to higher ABCG2 mRNA or protein levels. These results demonstrate the relevant effect of the Y581S polymorphism of the bovine ABCG2 transporter in the secretion into milk of danofloxacin after administration of 6mg/kg, with potentially important consequences for mastitis treatment and for milk residue handling. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Dicty_cDB: Contig-U16536-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available .. 410 e-110 1 ( AF307748 ) Tn10 delivery vector pHV1249 transposase, CAT, er... 410 e-110 1 ( CT025605 ) Mo... CU928144 |pid:none) Escherichia fergusonii str. ATCC ... 143 1e-32 AF307748_1( AF307748 |pid:none) Tn10 delivery

ɛ '/ ɛ anomaly and neutron EDM in SU(2) L × SU(2) R × U(1) B- L model with charge symmetry

Science.gov (United States)

Haba, Naoyuki; Umeeda, Hiroyuki; Yamada, Toshifumi

2018-05-01

The Standard Model prediction for ɛ '/ ɛ based on recent lattice QCD results exhibits a tension with the experimental data. We solve this tension through W R + gauge boson exchange in the SU(2) L × SU(2) R × U(1) B- L model with `charge symmetry', whose theoretical motivation is to attribute the chiral structure of the Standard Model to the spontaneous breaking of SU(2) R × U(1) B- L gauge group and charge symmetry. We show that {M_W}{_R}study a correlation between ɛ ' /ɛ and the neutron EDM. We confirm that the model can solve the ɛ ' /ɛ anomaly without conflicting the current bound on the neutron EDM, and further reveal that almost all parameter regions in which the ɛ ' /ɛ anomaly is explained will be covered by future neutron EDM searches, which leads us to anticipate the discovery of the neutron EDM.

Dicty_cDB: Contig-U13443-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available lignments: (bits) Value N ( AF305060 ) Dictyostelium discoideum Wiscott-Aldrich syndrome... 529 0.0 10 ( BJ3... AF305060 ) Dictyostelium discoideum Wiscott-Aldrich syndrome protein (wasA) gene...icant alignments: (bits) Value AF305060_1( AF305060 |pid:none) Dictyostelium discoideum Wiscott...0_1( AF305060 |pid:none) Dictyostelium discoideum Wiscott-Aldrich syndrome protein (wasA) gene, complete cds

Gastrin regulates ABCG2 to promote the migration, invasion and side populations in pancreatic cancer cells via activation of NF-κB signaling

Energy Technology Data Exchange (ETDEWEB)

Wang, Juan; Xin, Beibei; Wang, Hui; He, Xiaodan [School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071 (China); Wei, Wei; Zhang, Ti [Tianjin Medical University Cancer Institute and Hospital, Huanhu West Road, Tianjin 300060 (China); Shen, Xiaohong, E-mail: zebal2014@163.com [School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071 (China)

2016-08-01

Gastrin is absent in most normal adult pancreatic tissues but is highly expressed in pancreatic cancer tissues. Although Gastrin expression was reported to be associated with tumor proliferation in human pancreatic cancer, studies on the relationship between Gastrin and tumor metastasis in pancreatic cancer are rare. In this study, we performed an analysis to determine the effects of Gastrin on modulating the side populations, cell proportion and tumor cell metastatic potential and invasion activity and explored its mechanisms in pancreatic cancer. We indicated that Gastrin and ABCG2 were widely expressed in pancreatic cancer cell lines and overexpressed in cancer tissues. Gastrin induced ABCG2 expression, and this effect was mediated by NF-κB activation. Gastrin regulated the SP proportion of BxPC-3 cells via modulating ABCG2 expression. Through the regulation of the functions of NF-κB/ABCG2, Gastrin functionally promoted the migration and invasion in pancreatic cancer cell. The present study indicated that Gastrin induced ABCG2 expression by activating NF-κB and thereby modulated the SP proportion, tumor cell metastatic potential and invasion activity in pancreatic cancer. Gastrin could serve as an effective therapeutic target for the metastasis of pancreatic cancer. - Highlights: • Gastrin induces ABCG2 expression mediated by NF-κB activation. • Gastrin regulates NF-κB's function that binds to the ABCG2 promoter in BxPC-3 cells. • Gastrin promotes the SP proportion in BxPC-3 cells by modulating ABCG2 expression via activation of NF-κB molecule. • Gastrin induces an increase in migration and invasion potential in pancreatic cancer cell by regulating NF-κB/ABCG2 signaling.

Genome-wide Identification and Expression Analysis of Half-size ABCG Genes in Malus × domestica

Directory of Open Access Journals (Sweden)

Juanjuan MA

2018-03-01

Full Text Available Half-size adenosine triphosphate-binding cassette transporter subgroup G (ABCG genes play crucial roles in regulating the movements of a variety of substrates and have been well studied in several plants. However, half-size ABCGs have not been characterized in detail in apple (Malus × domestica Borkh.. Here, we performed a genome-wide identification and expression analysis of the half-size ABCG gene family in apple. A total of 46 apple half-size ABCGs were identified and divided into six clusters according to the phylogenetic analysis. A gene structural analysis showed that most half-size ABCGs in the same cluster shared a similar exon–intron organization. A gene duplication analysis showed that segmental, tandem and whole-genome duplications could account for the expansion of half-size ABCG transporters in M. domestica. Moreover, a promoter scan, digital expression analysis and RNA-seq revealed that MdABCG21 may be involved in root's cytokinin transport and that ABCG17 may be involved in the lateral bud development of M. spectabilis ‘Bly114’ by mediating cytokinin transport. The data presented here lay the foundation for further investigations into the biological and physiological processes and functions of half-size ABCG genes in apple. Keywords: apple, ABCG gene, duplication, gene expression

11 CFR 101.1 - Candidate designations (2 U.S.C. 432(e)(1)).

Science.gov (United States)

2010-01-01

... 11 Federal Elections 1 2010-01-01 2010-01-01 false Candidate designations (2 U.S.C. 432(e)(1)). 101.1 Section 101.1 Federal Elections FEDERAL ELECTION COMMISSION GENERAL CANDIDATE STATUS AND... and address, party affiliation, and office sought, the District and State in which Federal office is...

Endothelial ATP-binding cassette G1 in mouse endothelium protects against hemodynamic-induced atherosclerosis

Energy Technology Data Exchange (ETDEWEB)

Xue, Shanshan [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Department of Pediatrics, Baodi District People’s Hospital of Tianjin City, Tianjin, 301800 (China); Wang, Jiaxing [Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 (China); Zhang, Xu; Shi, Ying; Li, Bochuan; Bao, Qiankun [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Pang, Wei [Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 (China); Ai, Ding [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Zhu, Yi [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 (China); He, Jinlong, E-mail: hejinlong@tmu.edu.cn [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China)

2016-08-19

Activated vascular endothelium inflammation under persistent hyperlipidemia is the initial step of atherogenesis. ATP-binding cassette G1 (ABCG1) is a crucial factor maintaining sterol and lipid homeostasis by transporting cholesterol efflux to high-density lipoprotein. In this study, we investigated the protective effects of ABCG1 in endothelial inflammation activation during early-stage atherogenesis in mice and the underlying mechanisms. Endothelial cell (EC)-specific ABCG1 transgenic (EC-ABCG1-Tg) mice were generated and cross-bred with low-density lipoprotein receptor–deficient (Ldlr{sup −/−}) mice. After a 4-week Western-type diet, the mice were sacrificed for assessing atherosclerosis. Human umbilical vein ECs were treated with different flows, and ABCG1 was adenovirally overexpressed to investigate the mechanism in vitro. Compared with Ldlr{sup −/−} mouse aortas, EC-ABCG1-Tg/Ldlr{sup −/−} aortas showed decreased early-stage lesions. Furthermore, the lesion area in the EC-ABCG1-Tg/Ldlr{sup −/−} mouse aortic arch but not thoracic aorta was significantly reduced, which suggests a protective role of ABCG1 under atheroprone flow. In vitro, overexpression of ABCG1 attenuated EC activation caused by oscillatory shear stress. Overexpression of ABCG1 blunted cholesterol-activated ECs in vitro. In exploring the mechanisms of ABCG1 attenuating endothelial inflammation, we found that ABCG1 inhibited oscillatory flow-activated nuclear factor kappa B and NLRP3 inflammasome in ECs. ABCG1 may play a protective role in early-stage atherosclerosis by reducing endothelial activation induced by oscillatory shear stress via suppressing the inflammatory response. - Highlights: • EC-ABCG1-Tg mice in a Ldlr{sup −/−} background showed decreased atherosclerosis. • Overexpression of ABCG1 in ECs decreased OSS-induced EC activation. • NLRP3 and NF-κB might be an underlying mechanism of ABCG1 protective role.

Dicty_cDB: Contig-U10778-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 75_1( AF399175 |pid:none) Eutintinnus pectinis clone Epec99a... 246 e-123 AM168471_1( AM168471 |pid:none) Di...one) Mallomonas papillosa clone H9 alph... 256 e-122 AF399172_1( AF399172 |pid:none) Eutintinnus pectinis cl

CIR, a corepressor of CBF1, binds to PAP-1 and effects alternative splicing

International Nuclear Information System (INIS)

Maita, Hiroshi; Kitaura, Hirotake; Ariga, Hiroyoshi; Iguchi-Ariga, Sanae M.M.

2005-01-01

We have reported that PAP-1, a product of a causative gene for autosomal retinitis pigmentosa, plays a role in splicing. In this study, CIR, a protein originally identified as a CBF1-interacting protein and reported to act as a transcriptional corepressor, was identified as a PAP-1 binding protein and its function as a splicing factor was investigated. In addition to a basic lysine and acidic serine-rich (BA) domain and a zinc knuckle-like motif, CIR has an arginine/serine dipeptide repeat (RS) domain in its C terminal region. The RS domain has been reported to be present in the superfamily of SR proteins, which are involved in splicing reactions. We generated CIR mutants with deletions of each BA and RS domain and studied their subcellular localizations and interactions with PAP-1 and other SR proteins, including SC35, SF2/ASF, and U2AF 35 . CIR was found to interact with U2AF 35 through the BA domain, with SC35 and SF2/ASF through the RS domain, and with PAP-1 outside the BA domain in vivo and in vitro. CIR was found to be colocalized with SC35 and PAP-1 in nuclear speckles. Then the effect of CIR on splicing was investigated using the E1a minigene as a reporter in HeLa cells. Ectopic expression of CIR with the E1a minigene changed the ratio of spliced isoforms of E1a that were produced by alternative selection of 5'-splice sites. These results indicate that CIR is a member of the family of SR-related proteins and that CIR plays a role in splicing regulation

Monoclonal Antibodies Directed toward the Hepatitis C Virus Glycoprotein E2 Detect Antigenic Differences Modulated by the N-Terminal Hypervariable Region 1 (HVR1), HVR2, and Intergenotypic Variable Region.

Science.gov (United States)

Alhammad, Yousef; Gu, Jun; Boo, Irene; Harrison, David; McCaffrey, Kathleen; Vietheer, Patricia T; Edwards, Stirling; Quinn, Charles; Coulibaly, Fásseli; Poumbourios, Pantelis; Drummer, Heidi E

2015-12-01

Hepatitis C virus (HCV) envelope glycoproteins E1 and E2 form a heterodimer and mediate receptor interactions and viral fusion. Both E1 and E2 are targets of the neutralizing antibody (NAb) response and are candidates for the production of vaccines that generate humoral immunity. Previous studies demonstrated that N-terminal hypervariable region 1 (HVR1) can modulate the neutralization potential of monoclonal antibodies (MAbs), but no information is available on the influence of HVR2 or the intergenotypic variable region (igVR) on antigenicity. In this study, we examined how the variable regions influence the antigenicity of the receptor binding domain of E2 spanning HCV polyprotein residues 384 to 661 (E2661) using a panel of MAbs raised against E2661 and E2661 lacking HVR1, HVR2, and the igVR (Δ123) and well-characterized MAbs isolated from infected humans. We show for a subset of both neutralizing and nonneutralizing MAbs that all three variable regions decrease the ability of MAbs to bind E2661 and reduce the ability of MAbs to inhibit E2-CD81 interactions. In addition, we describe a new MAb directed toward the region spanning residues 411 to 428 of E2 (MAb24) that demonstrates broad neutralization against all 7 genotypes of HCV. The ability of MAb24 to inhibit E2-CD81 interactions is strongly influenced by the three variable regions. Our data suggest that HVR1, HVR2, and the igVR modulate exposure of epitopes on the core domain of E2 and their ability to prevent E2-CD81 interactions. These studies suggest that the function of HVR2 and the igVR is to modulate antibody recognition of glycoprotein E2 and may contribute to immune evasion. This study reveals conformational and antigenic differences between the Δ123 and intact E2661 glycoproteins and provides new structural and functional data about the three variable regions and their role in occluding neutralizing and nonneutralizing epitopes on the E2 core domain. The variable regions may therefore function to

Magnetic properties of U(Ni1-xCux)2Si2 solid solutions in the vicinity of x = 0.50 studied by neutron diffraction and AC-susceptibility

International Nuclear Information System (INIS)

Kuznietz, M.; Andre, G.; Bouree, F.; Pinto, H.; Ettedgui, H.; Melamud, M.

1993-01-01

The magnetic properties of two U(Ni 1-x Cu x ) 2 Si 2 solid in the vicinity of x = 0.50 (denoted I and II) have been studied by neutron diffraction and ac-susceptibility. Both materials have ThCr 2 Si 2 -type crystallographic structure. AC-susceptibility shows antiferromagnetic transitions at T N 150±5 K in UNiCuSi 2 (I) and 155±5 K in UNiCuSi 2 (II), followed by several transitions with ferrimagnetic (F) character at lower temperatures. Apart from the transitions to AF-I structure at T N =150K and 152K none of the F transitions is observed by neutron diffraction. Short-range magnetic order, involving several consecutive ferromagnetic planes or ferrimagnetic groups of planes in the AF-I phase, detected by ac-susceptibility and not by neutron diffraction in both materials and therefore significant to x ∼ 0.50, is proposed to explain the unusual susceptibility. (Author)

Dicty_cDB: Contig-U15766-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available AF250284 ) Amsacta moorei entomopoxvirus, complete genome. 34 2.6 17 ( CW609064 ) OA_ABa0149O20.f OA_ABa Oryza australie...6 8.9 7 ( CT561949 ) A BAC library has been constructed from cultivar ... 30 9.0 4 ( EK214431 ) 1095460111787 Global-Ocean-Sampli...277657 ) CITBI-E1-2518H21.TF CITBI-E1 Homo sapiens genomic... 46 9.2 1 ( EJ243648 ) 1095333029509 Global-Ocean-Sampli...cf*pnhlvqei*ckpfvp*wlrrqklnvpqrklikrpnki ypi*nmpyvnkf*qklkdsltilimfpmplvhpfynskrfhrqfqyfningqvlhhwmlq synn*m... AF538053 ) Monosiga brevicollis mitochondrion, complete genome. 34 0.10 12 ( EJ982583 ) 1093022164217 Global-Ocean-Sampli

Mutations of the central tyrosines of putative cholesterol recognition amino acid consensus (CRAC) sequences modify folding, activity, and sterol-sensing of the human ABCG2 multidrug transporter.

Science.gov (United States)

Gál, Zita; Hegedüs, Csilla; Szakács, Gergely; Váradi, András; Sarkadi, Balázs; Özvegy-Laczka, Csilla

2015-02-01

Human ABCG2 is a plasma membrane glycoprotein causing multidrug resistance in cancer. Membrane cholesterol and bile acids are efficient regulators of ABCG2 function, while the molecular nature of the sterol-sensing sites has not been elucidated. The cholesterol recognition amino acid consensus (CRAC, L/V-(X)(1-5)-Y-(X)(1-5)-R/K) sequence is one of the conserved motifs involved in cholesterol binding in several proteins. We have identified five potential CRAC motifs in the transmembrane domain of the human ABCG2 protein. In order to define their roles in sterol-sensing, the central tyrosines of these CRACs (Y413, 459, 469, 570 and 645) were mutated to S or F and the mutants were expressed both in insect and mammalian cells. We found that mutation in Y459 prevented protein expression; the Y469S and Y645S mutants lost their activity; while the Y570S, Y469F, and Y645F mutants retained function as well as cholesterol and bile acid sensitivity. We found that in the case of the Y413S mutant, drug transport was efficient, while modulation of the ATPase activity by cholesterol and bile acids was significantly altered. We suggest that the Y413 residue within a putative CRAC motif has a role in sterol-sensing and the ATPase/drug transport coupling in the ABCG2 multidrug transporter. Copyright © 2014. Published by Elsevier B.V.

Characterization of Sugarcane Mosaic Virus Scmv1 and Scmv2 Resistance Regions by Regional Association Analysis in Maize.

Directory of Open Access Journals (Sweden)

Pengfei Leng

Full Text Available Sugarcane Mosaic Virus (SCMV causes one of the most severe virus diseases in maize worldwide, resulting in reduced grain and forage yield in susceptible cultivars. In this study, two association panels consisting of 94 inbred lines each, from China and the U.S., were characterized for resistance to two isolates: SCMV-Seehausen and SCMV-BJ. The population structure of both association panels was analyzed using 3072 single nucleotide polymorphism (SNP markers. The Chinese and the U.S. panel were both subdivided into two sub-populations, the latter comprised of Stiff Stalk Synthetic (SS lines and Non Stiff Stalk Synthetic (NSS. The relative kinships were calculated using informative 2947 SNPs with minor allele frequency ≥ 5% and missing data ≤ 20% for the Chinese panel and 2841 SNPs with the same characteristics were used for the U.S. panel. The Scmv1 region was genotyped using 7 single sequence repeat (SSR and sequence-tagged site (STS markers, and 12 SSR markers were used for the Scmv2 region in the U.S. panel, while 5 of them were used for the Chinese panel. For all traits, a MLM (Mix Linear Model controlling both population structure and relative kinship (Q + K was used for association analysis. Three markers Trx-1, STS-11, and STS-12 located in the Scmv1 region were strongly associated (P = 0.001 with SCMV resistance, and explained more than 16.0%, 10.6%, and 19.7% of phenotypic variation, respectively. 207FG003 located in the Scmv2 region was significantly associated (P = 0.001 with SCMV resistance, and explained around 18.5% of phenotypic variation.

Dicty_cDB: Contig-U16119-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available ing pro... 80 9e-14 AB241248_1( AB241248 |pid:none) Symbiotic protist of Reticuliterme... 80 9e-14 BT033192_...3 AB241247_1( AB241247 |pid:none) Symbiotic protist of Reticuliterme... 80 1e-13 ( P90726 ) RecName: Full=Ra.... 79 4e-13 AB241241_1( AB241241 |pid:none) Symbiotic protist of Reticuliterme... 79 4e-13 CP000909_1207( CP0...e 2... 82 4e-14 AF461434_1( AF461434 |pid:none) Babesia gibsoni small GTP binding ... 82 4e-14 AB241242_1( AB241242 |pid:none) Symbio...tic protist of Reticuliterme... 82 4e-14 GN106155_1( GN1

Dicty_cDB: Contig-U06052-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 22_1( AF021822 |pid:none) Scaptodrosophila lebanonensis supe... 58 5e-07 ( P93407 ) RecName: Full=Superoxide...tase [Cu-Zn]; EC... 55 5e-06 AF021824_1( AF021824 |pid:none) Hirtodrosophila pictiventris super... 55 5e-06

Dicty_cDB: Contig-U11124-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available P000388_1017( CP000388 |pid:none) Pseudoalteromonas atlantica T6c... 112 4e-23 FM992689_561( FM992689 |pid:none) Candida dubliniensi...8e-46 AY310275_1( AY310275 |pid:none) Uroblaniulus canadensis voucher Pa... 187 8e-46 AY310266_1( AY310266 |pid:none) Lamyctes..... 157 1e-36 AY310255_1( AY310255 |pid:none) Docodesmus trinidadensis voucher D... 156 2e-36 AY305524_1( AY3................done Score E Sequences producing significant alignments: (bits) Value N ( BJ427602 ) Dictyostelium disc...AF248644_1( AF248644 |pid:none) Filobasidiella neoformans var. neo... 191 7e-47 BC059523_1( BC059523 |pid:none) Danio rerio si

U.2010 B.1; Fagforeningers kontrol af virksomheders løn- og arbejdsvilkår

DEFF Research Database (Denmark)

Lind, Martin Gräs

2010-01-01

Artiklen behandler spørgsmålet, om og i hvilket omfang fagforeninger har ret til at kontrollere især overenskomstforpligtede arbejdsgivere. Det stigende antal udenlandske arbejdstagere på det danske arbejdsmarked har medført øget fokus på og behov for kontrolførelse af overenskomstens bestemmelse......, bl.a. for at sikre mod illegal beskæftigelse, omgåelse af overenskomsterne og social dumping....

7 CFR 51.2541 - U.S. Fancy, U.S. Extra No. 1, U.S. No. 1 And U.S. Select Grades.

Science.gov (United States)

2010-01-01

... PRODUCTS 1,2 (INSPECTION, CERTIFICATION, AND STANDARDS) United States Standards for Grades of Pistachio.... Fancy,” “U.S. Extra No. 1,” “U.S. No. 1,” and “U.S. Select” consists of pistachio nuts in the shell...

Membrane Separation of 2-Ethyl Hexyl Amine/1-Decene

KAUST Repository

Bawareth, Bander

2012-01-01

in this environment with reasonable and stable separation factor. This paper shows that Teflon AF 2400 and cellulose acetate produced interesting results in 1-decene/2-EHA separation. The separation factor of Teflon AF 2400 is 3 with a stable permeance of 1.1x10-2 L

Dicty_cDB: Contig-U14682-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available nslandica notch mRN... 39 1.4 AF533016_1( AF533016 |pid:none) Salmo salar hyperosmo.... 39 1.4 AK289553_1( AK289553 |pid:none) Homo sapiens cDNA FLJ76207 complet... 39 1.4 EU273942_1( EU273942 |pid:none) Amphimedon quee

Analyse af IPCC delrapport 2 - Effekter, klimatilpasning og sårbarhed

DEFF Research Database (Denmark)

Christensen, Jens Hesselbjerg; Arnbjerg-Nielsen, Karsten; Grindsted, Aslak

. Med afsæt i denne delrapport er der udarbejdet en dansk analyse, der nærmere beskriver effekterne af et ændret klima i Danmark suppleret med den seneste danske forskning udført af det danske Center for Regional Changes in the Earth System (CRES). ”Analyse af IPCC delrapport 2 – Effekter...

Dicty_cDB: Contig-U15007-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available ezuelae desosamine... 52 6e-05 AF055579_5( AF055579 |pid:none) Streptomyces antibio...94 |pid:none) Bradyrhizobium sp. BTAi1, compl... 52 5e-05 AF079762_6( AF079762 |pid:none) Streptomyces ven

Synthesis of (R)-5-(Di[2,3-3H2]propylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one-([3H]U-86170) and (R)-5-([2,3-3H2]propylamino)-5,6-dihydro-4H-imidazo(4,5,1-ij) quinolin-2(1H)-one ([3H]U-91356)

International Nuclear Information System (INIS)

Moon, M.W.; Hsi, R.S.P.

1992-01-01

(R)-5-(diallylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (12b) was prepared in 9% overall yield from 3-aminoquinoline. Reaction of 12b in ethyl acetate with tritium gas in presence of a 5% platinum on carbon catalyst afforded a mixture of (R)-5-(di[2,3- 3 H 2 ]propylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]-quinolin-2(1H)-one ([ 3 H]U-86170, 69 Ci/mmol) and (R)-5-([2,3- 3 H 2 ]-propylamino)5,6-dihydro-4H-imidazo-[4,5,1-ij]quinolin-2(1H)-one ( [ 3 H]U-91356, 34 Ci/mmol) which was separated by preparative reverse-phase chromatography. U-86170 and U-91356 are potent dopamine D2 agonists. The labelled compounds are useful for drug disposition studies. [ 3 H]U-86170 is also useful as a dopamine D2 agonist radioligand for receptor binding studies. (author)

The naphthoquinones, vitamin K3 and its structural analog plumbagin, are substrates of the multidrug resistance-linked ABC drug transporter ABCG2

OpenAIRE

Shukla, Suneet; Wu, Chung-Pu; Nandigama, Krishnamachary; Ambudkar, Suresh V.

2007-01-01

Vitamin K3 (Menadione; 2-methyl-1,4-naphthoquinone) is a structural precursor of vitamins K1 and K2 which are essential for blood clotting. The naturally occurring structural analog of this vitamin, plumbagin (5-hydroxy-menadione), is known to modulate cellular proliferation, apoptosis, carcinogenesis, and radioresistance. We, here, report that both vitamin K3 and plumbagin are substrates of the multidrug resistance-linked ATP binding cassette (ABC) drug transporter, ABCG2. Vitamin K3 and plu...

U1 Adaptor Oligonucleotides Targeting BCL2 and GRM1 Suppress Growth of Human Melanoma Xenografts In Vivo

Directory of Open Access Journals (Sweden)

Rafal Goraczniak

2013-01-01

Full Text Available U1 Adaptor is a recently discovered oligonucleotide-based gene-silencing technology with a unique mechanism of action that targets nuclear pre-mRNA processing. U1 Adaptors have two distinct functional domains, both of which must be present on the same oligonucleotide to exert their gene-silencing function. Here, we present the first in vivo use of U1 Adaptors by targeting two different human genes implicated in melanomagenesis, B-cell lymphoma 2 (BCL2 and metabotropic glutamate receptor 1 (GRM1, in a human melanoma cell xenograft mouse model system. Using a newly developed dendrimer delivery system, anti-BCL2 U1 Adaptors were very potent and suppressed tumor growth at doses as low as 34 µg/kg with twice weekly intravenous (iv administration. Anti-GRM1 U1 Adaptors suppressed tumor xenograft growth with similar potency. Mechanism of action was demonstrated by showing target gene suppression in tumors and by observing that negative control U1 Adaptors with just one functional domain show no tumor suppression activity. The anti-BCL2 and anti-GRM1 treatments were equally effective against cell lines harboring either wild-type or a mutant V600E B-RAF allele, the most common mutation in melanoma. Treatment of normal immune-competent mice (C57BL6 indicated no organ toxicity or immune stimulation. These proof-of-concept studies represent an in-depth (over 800 mice in ~108 treatment groups validation that U1 Adaptors are a highly potent gene-silencing therapeutic and open the way for their further development to treat other human diseases.

Underground storage tank 291-D1U1: Closure plan

Energy Technology Data Exchange (ETDEWEB)

Mancieri, S.; Giuntoli, N.

1993-09-01

The 291-D1U1 tank system was installed in 1983 on the north side of Building 291. It supplies diesel fuel to the Building 291 emergency generator and air compressor. The emergency generator and air compressor are located southwest and southeast, respectively, of the tank (see Appendix B, Figure 2). The tank system consists of a single-walled, 2,000- gallon, fiberglass tank and a fuel pump system, fill pipe, vent pipe, electrical conduit, and fuel supply and return piping. The area to be excavated is paved with asphalt and concrete. It is not known whether a concrete anchor pad is associated with this tank. Additionally, this closure plan assumes that the diesel tank is below the fill pad. The emergency generator and air compressor for Building 291 and its associated UST, 291-D1U1, are currently in use. The generator and air compressor will be supplied by a temporary above-ground fuel tank prior to the removal of 291-D1U1. An above-ground fuel tank will be installed as a permanent replacement for 291-D1U1. The system was registered with the State Water Resources Control Board on June 27, 1984, as 291-41D and has subsequently been renamed 291-D1U1. Figure 1 (see Appendix B) shows the location of the 291-D1U1 tank system in relation to the Lawrence Livermore National Laboratory (LLNL). Figure 2 (see Appendix B) shows the 291-D1U1 tank system in relation to Building 291. Figure 3 (see Appendix B) shows a plan view of the 291-D1U1 tank system.

Tank 241-U-102, Grab Samples 2U-99-1, 2U-99-2 and 2U-99-3 Analytical Results for the Final Report

International Nuclear Information System (INIS)

STEEN, F.H.

1999-01-01

This document is the final report for tank 241-U-102 grab samples. Five grab samples were collected from riser 13 on May 26, 1999 and received by the 222-S laboratory on May 26 and May 27, 1999. Samples 2U-99-3 and 2U-99-4 were submitted to the Process Chemistry Laboratory for special studies. Samples 2U-99-1, 2U-99-2 and 2U-99-5 were submitted to the laboratory for analyses. Analyses were performed in accordance with the Compatibility Grab Sampling and Analysis Plan for Fiscal year 1999 (TSAP) (Sasaki, 1999) and the Data Quality Objectives for Tank Farms Waste Compatibility Program (DQO) (Fowler 1995, Mulkey and Miller 1998). The analytical results are presented in the data summary report. None of the subsamples submitted for differential scanning calorimetry (DSC), total organic carbon (TOC) and plutonium 239 (Pu239) analyses exceeded the notification limits as stated in TSAP

Dicty_cDB: Contig-U03036-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available DQ379469 ) Concholepas concholepas microsatellite Cc1H2 sequ... 50 0.17 1 ( AF10...e DKEY-65O14 in l... 50 0.17 1 ( AC118018 ) Mus musculus chromosome 17, clone RP23-458D20, co... 50 0.17 1 (

Cichorium intybus L. promotes intestinal uric acid excretion by modulating ABCG2 in experimental hyperuricemia.

Science.gov (United States)

Wang, Yu; Lin, Zhijian; Zhang, Bing; Nie, Anzheng; Bian, Meng

2017-01-01

Excessive production and/or reduced excretion of uric acid could lead to hyperuricemia, which could be a major cause of disability. Hyperuricemia has received increasing attention in the last few decades due to its global prevalence. Cichorium intybus L., commonly known as chicory, is a perennial herb of the asteraceae family. It was previously shown to exert potent hypouricemic effects linked with decreasing uric acid formation in the liver by down-regulating the activity of xanthine oxidase, and increasing uric acid excretion by up-regulating the renal OAT3 mRNA expression. The present study aimed to evaluate its extra-renal excretion and possible molecular mechanism underlying the transporter responsible for intestinal uric acid excretion in vivo. Chicory was administered intragastrically to hyperuricemic rats induced by drinking 10% fructose water. The uricosuric effect was evaluated by determining the serum uric acid level as well as the intestinal uric acid excretion by HPLC. The location and expression levels of ATP-binding cassette transporter, sub-family G, member 2 (ABCG2) in jejunum and ileum were analyzed. The administration of chicory decreased the serum uric acid level significantly and increased the intestinal uric acid excretion obviously in hyperuricemic rats induced by 10% fructose drinking. Staining showed that ABCG2 was expressed in the apical membrane of the epithelium and glands of the jejunum and ileum in rats. Further examination showed that chicory enhanced the mRNA and protein expressions of ABCG2 markedly in a dose-dependent manner in jejunum and ileum. These findings indicate that chicory increases uric acid excretion by intestines, which may be related to the stimulation of intestinal uric acid excretion via down-regulating the mRNA and protein expressions of ABCG2.

Supersymmetric U boson and the old U(1) problem

International Nuclear Information System (INIS)

Kim, B.R.

1983-01-01

In the supersymmetric SU(3)xSU(2)xU(1)xUsup(')(1) model the new gauge group Usup(')(1) enforces the introduction of mirror fermions. In this note we address the inverse question. If one starts with SU(3)xSU(2)xU(1) including mirror fermions, what physical arguments other than the supersymmetric require the introduction of a new gauge group Usup(')(1). It turns out that the old U(1) problem is closely related with this question. Further we give an estimate for the upper bound for the parameter of the supersymmetric U boson r and x. (orig.)

Dicty_cDB: Contig-U08441-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available ... 64 5e-09 AF049900_1( AF049900 |pid:none) Lycopersicon esculentum gibberelli... 64 5e-09 AY622311_1( AY622311 |pid:none) Rhodotoru...la glutinis thymine dioxy... 64 5e-09 AB010953_1( AB0109

Dicty_cDB: Contig-U11302-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available .. 304 e-140 EU128481_1( EU128481 |pid:none) Tanichthys albonubes beta-actin mR... 304 e-140 AF368030_1( AF3...actin gene... 307 e-139 EU128482_1( EU128482 |pid:none) Tanichthys albonubes beta

Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP.

Directory of Open Access Journals (Sweden)

Helena Hernández

2009-09-01

Full Text Available Most human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post-translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle. Using mass spectrometry we investigate the composition and dynamics of the native human U1 snRNP and compare native and recombinant complexes to isolate the effects of various subunits and isoforms on the overall stability. Our data reveal differential incorporation of four protein isoforms and dynamic interactions of subunits U1-A, U1-C and Sm-B/B'. Results also show that unstructured post-translationally modified C-terminal tails are responsible for the dynamics of Sm-B/B' and U1-C and that their interactions with the Sm core are controlled by binding to different U1-70k isoforms and their phosphorylation status in vivo. These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function.

Beta1 integrin inhibits apoptosis induced by cyclic stretch in annulus fibrosus cells via ERK1/2 MAPK pathway.

Science.gov (United States)

Zhang, Kai; Ding, Wei; Sun, Wei; Sun, Xiao-jiang; Xie, You-zhuan; Zhao, Chang-qing; Zhao, Jie

2016-01-01

Low back pain is associated with intervertebral disc degeneration (IVDD) due to cellular loss through apoptosis. Mechanical factors play an important role in maintaining the survival of the annulus fibrosus (AF) cells and the deposition of extracellular matrix. However, the mechanisms that excessive mechanical forces lead to AF cell apoptosis are not clear. The present study was to look for how AF cells sense mechanical changes. In vivo experiments, the involvement of mechanoreceptors in apoptosis was examined by RT-PCR and/or immunoblotting in the lumbar spine of rats subjected to unbalanced dynamic and static forces. In vitro experiments, we investigated apoptotic signaling pathways in untransfected and transfected AF cells with the lentivirus vector for rat β1 integrin overexpression after cyclic stretch. Apoptosis in AF cells was assessed using flow cytometry, Hoechst 33258 nuclear staining. Western blotting was used to analyze expression of β1 integrin and caspase-3 and ERK1/2 MAPK signaling molecules. In the rat IVDD model, unbalanced dynamic and static forces induced apoptosis of disc cells, which corresponded to decreased expression of β1 integrin. Cyclic stretch-induced apoptosis in rat AF cells correlated with the activation of caspase-3 and with decreased levels of β1 integrin and the phosphorylation levels of ERK1/2 activation level. However, the overexpression of β1 integrin in AF cells ameliorated cyclic stretch-induced apoptosis and decreased caspase-3 activation. Furthermore, ERK1/2-specific inhibitor promotes apoptosis in vector β1-infected AF cells. These results suggest that the disruption of β1 integrin signaling may underlie disc cell apoptosis induced by mechanical stress. Further work is necessary to fully elucidate the pathophysiological mechanisms that underlie IVDD caused by unbalanced dynamic and static forces.

Structure and Lamb shift of 2s1/2-2p3/2 levels in lithiumlike U89+ through neonlike U82+

International Nuclear Information System (INIS)

Beiersdorfer, P.; Knapp, D.; Marrs, R.E.; Elliott, S.R.; Chen, M.H.

1993-01-01

The first Doppler-shift-free crystal-spectrometer measurement of stationary highly stripped uranium ions from a high-energy electron beam ion trap is presented. Thirteen 2s 1/2- 2p 3/2 transitions in eight ionization states bteween Li-like U 89+ and Ne-like U 82+ are identified and measured with an accuracy as high as 37 ppm, providing benchmarks for testing relativistic correlation and quantum electrodynamic effects in highly charged multielectron ions. A value of 47.39±0.35 eV is found for the 2s 1/2 Lamb shift in Li-like U 89+ , in excellent agreement with theory

Structure and lamb shift of 2s1/2-2p3/2 levels in lithiumlike U89+ through neonlike U82+

International Nuclear Information System (INIS)

Beiersdorfer, P.; Knapp, D.; Marrs, R.E.; Elliott, S.; Chen, M.H.

1993-01-01

The first Doppler-shift-free crystal- spectrometer measurements from stationary highly stripped uranium ions are presented. Eleven 2s 1/2 -2p 3/2 transitions in eight ionization stages between Li-like U 89+ and Ne-like U 82+ are identified and measured with an accuracy as high as 45 ppm, providing benchmarks for testing relativistic correlation and quantum electrodynamical effects in highly charged multi-electron ions. A value of 47.38 ± 0.35 eV is found for the 2s 1/2 Lamb shift in Li-like U 89+ , in excellent agreement with the theoretical value of 47.58 eV

Interaction with the 5D3 monoclonal antibody is regulated by intramolecular rearrangements but not by covalent dimer formation of the human ABCG2 multidrug transporter

DEFF Research Database (Denmark)

Özvegy-Laczka, Csilla; Laczkó, Rozália; Hegedűs, Csilla

2008-01-01

D3 monoclonal antibody shows a function-dependent reactivity to an extracellular epitope of the ABCG2 transporter. In the current experiments we have further characterized the 5D3-ABCG2 interaction. The effect of chemical cross-linking and the modulation of extracellular S-S bridges...... on the transporter function and 5D3 reactivity of ABCG2 were investigated in depth. We found that several protein cross-linkers greatly increased 5D3 labeling in ABCG2 expressing HEK cells; however, there was no correlation between covalent dimer formation, the inhibition of transport activity, and the increase in 5...

3D nuclear organization of telomeres in the Hodgkin cell lines U-HO1 and U-HO1-PTPN1: PTPN1 expression prevents the formation of very short telomeres including "t-stumps"

Directory of Open Access Journals (Sweden)

Lemieux Bruno

2010-12-01

Full Text Available Abstract Background In cancer cells the three-dimensional (3D telomere organization of interphase nuclei into a telomeric disk is heavily distorted and aggregates are found. In Hodgkin's lymphoma quantitative FISH (3D Q-FISH reveals a major impact of nuclear telomere dynamics during the transition form mononuclear Hodgkin (H to diagnostic multinuclear Reed-Sternberg (RS cells. In vitro and in vivo formation of RS-cells is associated with the increase of very short telomeres including "t-stumps", telomere loss, telomeric aggregate formation and the generation of "ghost nuclei". Results Here we analyze the 3D telomere dynamics by Q-FISH in the novel Hodgkin cell line U-HO1 and its non-receptor protein-tyrosine phosphatase N1 (PTPN1 stable transfectant U-HO1-PTPN1, derived from a primary refractory Hodgkin's lymphoma. Both cell lines show equally high telomerase activity but U-HO1-PTPN differs from U-HO1 by a three times longer doubling time, low STAT5A expression, accumulation of RS-cells (p As expected, multinuclear U-HO1-RS-cells and multinuclear U-HO1-PTPN1-RS-cells differ from their mononuclear H-precursors by their nuclear volume (p Conclusion Abundant RS-cells without additional very short telomeres including "t-stumps", high rate of apoptosis, but low STAT5A expression, are hallmarks of the U-HO1-PTPN1 cell line. These characteristics are independent of telomerase activity. Thus, PTPN1 induced dephosphorylation of STAT5 with consecutive lack of Akt/PKB activation and cellular arrest in G2, promoting induction of apoptosis, appears as a possible pathogenetic mechanism deserving further experimental investigation.

Observation of the HH 1 and 2 region with IRAS

International Nuclear Information System (INIS)

Pravdo, S.H.; Chester, T.J.

1987-01-01

Infrared Astronomical Satellite (IRAS) observations of the region in Orion containing HH 1 and 2 reveal for the first time the large-scale distribution of newly formed stars. New infrared sources discovered in these observations are discussed, and attempts are made to untangle the complex infrared morphology of this field. A major finding of this study is that HH 1 is near the peak of an intense and broad plateau of 60 and 100 micron emission that spatially corresponds well with the boundaries of a previously detected molecular cloud. Other findings include the detection of an emitting circum-HH object dust complex around HH 2, 25 micron emission associated with the putative HH 1 and 2 exciting source discovered with the VLA, a new luminous far-infrared source, and numerous infrared source complexes, some in blank optical fields and others in fields containing optical emission-line stars. 37 references

Dicty_cDB: Contig-U02828-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available EU080666_1( EU080666 |pid:none) Phytophthora cuyabensis isolate PD... 73 3e-12 AF240877_1( AF240877 |pid:no...a isola... 73 3e-12 EU080373_1( EU080373 |pid:none) Phytophthora cuyabensis isolate PD... 73 3e-12 EU369017_

Development of a model for functional studies of ABCG2 (breast cancer resistance protein) efflux employing a standard BeWo clone (B24).

Science.gov (United States)

Crowe, Andrew; Keelan, Jeffrey A

2012-10-01

Human choriocarcinoma-derived BeWo cells express high levels of breast cancer resistance protein (BCRP/ABCG2) with no functional P-glycoprotein (P-gp) (ABCB1) activity, making them a potential model to study bidirectional ABCG2-mediated drug transport. However, the original BeWo clone (B24) available to researchers does not form confluent monolayers with tight junctions required by the model. Our aim was to adapt culture conditions to attempt to generate confluent BeWo monolayers for drug transport studies using the standard B24 clone. BeWo cells (B24; American Type Culture collection [ATCC]) were cultured in six-well plates or polycarbonate millicell inserts in a number of media formulations, growth supplements, and basement membrane substitutes. Cells were examined for confluence by microscopy, and transepithelial electrical resistance (TEER) was measured daily; monolayer permeability was assessed when TEER had stabilized. Optimal growth rates were achieved in culture conditions consisting of Medium 199 (M199) supplemented with epidermal growth factor (EGF; 20 ng/mL), vitamin supplements, and 10% fetal calf serum (FCS) with collagen coating. A TEER of 170 Ω in 0.6 cm(2) inserts was achieved 2 weeks after seeding under optimal conditions. The cell-impermeable diffusion marker 5(6) carboxy-2,7dichlorodihydrofluorescein (C-DCDHF) had a permeability coefficient of 3.5×10(-6) cm/s, indicative of minimal paracellular permeability. ABCG2 expression, as determined by immunoblotting, remained unaffected by confluency. In conclusion, we describe culture conditions for the B24 BeWo clone that facilitate the formation of monolayers with tighter junctions and reduced paracellular transport compared to previously published models. These growth conditions provide a good model of ABCG2-mediated drug transport in a human placental cell line.

EBV-Negative Monomorphic B-Cell Posttransplant Lymphoproliferative Disorder with Marked Morphologic Pleomorphism and Pathogenic Mutations in ASXL1, BCOR, CDKN2A, NF1, and TP53.

Science.gov (United States)

Bogusz, Agata M

2017-01-01

Posttransplant lymphoproliferative disorders (PTLDs) are a diverse group of lymphoid or plasmacytic proliferations frequently driven by Epstein-Barr virus (EBV). EBV-negative PTLDs appear to represent a distinct entity. This report describes an unusual case of a 33-year-old woman that developed a monomorphic EBV-negative PTLD consistent with diffuse large B-cell lymphoma (DLBCL) 13 years after heart-lung transplant. Histological examination revealed marked pleomorphism of the malignant cells including nodular areas reminiscent of classical Hodgkin lymphoma (cHL) with abundant large, bizarre Hodgkin-like cells. By immunostaining, the malignant cells were immunoreactive for CD45, CD20, CD79a, PAX5, BCL6, MUM1, and p53 and negative for CD15, CD30, latent membrane protein 1 (LMP1), and EBV-encoded RNA (EBER). Flow cytometry demonstrated lambda light chain restricted CD5 and CD10 negative B-cells. Fluorescence in situ hybridization studies (FISH) were negative for cMYC , BCL2, and BCL6 rearrangements but showed deletion of TP53 and monosomy of chromosome 17. Next-generation sequencing studies (NGS) revealed numerous genetic alterations including 6 pathogenic mutations in ASXL1, BCOR, CDKN2A, NF1, and TP53 (x2) genes and 30 variants of unknown significance (VOUS) in ABL1, ASXL1, ATM, BCOR, BCORL1, BRNIP3, CDH2, CDKN2A, DNMT3A, ETV6, EZH2, FBXW7, KIT, NF1, RUNX1, SETPB1, SF1, SMC1A, STAG2, TET2, TP53, and U2AF2.

EBV-Negative Monomorphic B-Cell Posttransplant Lymphoproliferative Disorder with Marked Morphologic Pleomorphism and Pathogenic Mutations in ASXL1, BCOR, CDKN2A, NF1, and TP53

Directory of Open Access Journals (Sweden)

Agata M. Bogusz

2017-01-01

Full Text Available Posttransplant lymphoproliferative disorders (PTLDs are a diverse group of lymphoid or plasmacytic proliferations frequently driven by Epstein-Barr virus (EBV. EBV-negative PTLDs appear to represent a distinct entity. This report describes an unusual case of a 33-year-old woman that developed a monomorphic EBV-negative PTLD consistent with diffuse large B-cell lymphoma (DLBCL 13 years after heart-lung transplant. Histological examination revealed marked pleomorphism of the malignant cells including nodular areas reminiscent of classical Hodgkin lymphoma (cHL with abundant large, bizarre Hodgkin-like cells. By immunostaining, the malignant cells were immunoreactive for CD45, CD20, CD79a, PAX5, BCL6, MUM1, and p53 and negative for CD15, CD30, latent membrane protein 1 (LMP1, and EBV-encoded RNA (EBER. Flow cytometry demonstrated lambda light chain restricted CD5 and CD10 negative B-cells. Fluorescence in situ hybridization studies (FISH were negative for cMYC, BCL2, and BCL6 rearrangements but showed deletion of TP53 and monosomy of chromosome 17. Next-generation sequencing studies (NGS revealed numerous genetic alterations including 6 pathogenic mutations in ASXL1, BCOR, CDKN2A, NF1, and TP53(x2 genes and 30 variants of unknown significance (VOUS in ABL1, ASXL1, ATM, BCOR, BCORL1, BRNIP3, CDH2, CDKN2A, DNMT3A, ETV6, EZH2, FBXW7, KIT, NF1, RUNX1, SETPB1, SF1, SMC1A, STAG2, TET2, TP53, and U2AF2.

En procesorienteret miljøvurdering af F&U

DEFF Research Database (Denmark)

Lyhne, Ivar

Miljøperformance af fremtidens energiteknologier defineres i høj grad i de tidlige F&U aktiviteter. Energinet.dk har i flere år miljøvurderet ForskEL-programmet og i dette projekt forbedres systemets nytte ved at muliggøre øgede krav til programmets samlede performance og følge op på projekternes...

U(1) x U(1) x U(1) symmetry of the Kimura 3ST model and phylogenetic branching processes

International Nuclear Information System (INIS)

Bashford, J D; Jarvis, P D; Sumner, J G; Steel, M A

2004-01-01

An analysis of the Kimura 3ST model of DNA sequence evolution is given on the basis of its continuous Lie symmetries. The rate matrix commutes with a U(1) x U(1) x U(1) phase subgroup of the group GL(4) of 4 x 4 invertible complex matrices acting on a linear space spanned by the four nucleic acid base letters. The diagonal 'branching operator' representing speciation is defined, and shown to intertwine the U(1) x U(1) x U(1) action. Using the intertwining property, a general formula for the probability density on the leaves of a binary tree under the Kimura model is derived, which is shown to be equivalent to established phylogenetic spectral transform methods. (letter to the editor)

Additive composite ABCG2, SLC2A9 and SLC22A12 scores of high-risk alleles with alcohol use modulate gout risk.

Science.gov (United States)

Tu, Hung-Pin; Chung, Chia-Min; Min-Shan Ko, Albert; Lee, Su-Shin; Lai, Han-Ming; Lee, Chien-Hung; Huang, Chung-Ming; Liu, Chiu-Shong; Ko, Ying-Chin

2016-09-01

The aim of the present study was to evaluate the contribution of urate transporter genes and alcohol use to the risk of gout/tophi. Eight variants of ABCG2, SLC2A9, SLC22A12, SLC22A11 and SLC17A3 were genotyped in male individuals in a case-control study with 157 gout (33% tophi), 106 asymptomatic hyperuricaemia and 295 control subjects from Taiwan. The multilocus profiles of the genetic risk scores for urate gene variants were used to evaluate the risk of asymptomatic hyperuricaemia, gout and tophi. ABCG2 Q141K (T), SLC2A9 rs1014290 (A) and SLC22A12 rs475688 (C) under an additive model and alcohol use independently predicted the risk of gout (respective odds ratio for each factor=2.48, 2.03, 1.95 and 2.48). The additive composite Q141K, rs1014290 and rs475688 scores of high-risk alleles were associated with gout risk (Pgout and tophi risk (P for interaction=0.0452, 0.0033). The synergistic effect of genetic urate score 5-6 and alcohol use indicates that these combined factors correlate with gout and tophi occurrence.

Dicty_cDB: Contig-U16312-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available nslandica notch mRN... 70 4e-10 AB001327_1( AB001327 |pid:none) Halocynthia roretzi... 4e-10 AF247637_1( AF247637 |pid:none) Mus musculus LDLR dan mRNA, comple... 70 4e-10 EU273942_1( EU273942 |pid:none) Amphimedon quee

SU(3)_C× SU(2)_L× U(1)_Y( × U(1)_X ) as a symmetry of division algebraic ladder operators

Science.gov (United States)

Furey, C.

2018-05-01

We demonstrate a model which captures certain attractive features of SU(5) theory, while providing a possible escape from proton decay. In this paper we show how ladder operators arise from the division algebras R, C, H, and O. From the SU( n) symmetry of these ladder operators, we then demonstrate a model which has much structural similarity to Georgi and Glashow's SU(5) grand unified theory. However, in this case, the transitions leading to proton decay are expected to be blocked, given that they coincide with presumably forbidden transformations which would incorrectly mix distinct algebraic actions. As a result, we find that we are left with G_{sm} = SU(3)_C× SU(2)_L× U(1)_Y / Z_6. Finally, we point out that if U( n) ladder symmetries are used in place of SU( n), it may then be possible to find this same G_{sm}=SU(3)_C× SU(2)_L× U(1)_Y / Z_6, together with an extra U(1)_X symmetry, related to B-L.

Topological ferrimagnetic behaviours of coordination polymers containing manganese(II) chains with mixed azide and carboxylate bridges and alternating F/AF/AF'/AF'/AF interactions.

Science.gov (United States)

Wang, Yan-Qin; Liu, Hou-Ting; Qi, Yan; Gao, En-Qing

2014-08-21

Two Mn(ii) complexes with azide and a new zwitterionic tetracarboxylate ligand 1,2,4,5-tetrakis(4-carboxylatopyridinium-1-methylene)benzene (L(1)), {[Mn5(L(1))2(N3)8(OH)2]·12H2O}n () and {[Mn5(L(1))2(N3)8(H2O)2](ClO4)2·6H2O}n (), have been synthesized and characterized crystallographically and magnetically. and contain similar alternating chains constructed by azide and carboxylate bridges. The independent sets of bridges alternate in an ABCCB sequence between adjacent Mn(ii) ions: (EO-N3)2 double bridges (EO = end-on) (denoted as A), [(EO-N3)(OCO)2] triple bridges (denoted as B) and [(EO-N3)(OCO)] double bridges (denoted as C). The alternating chains are interlinked into 2D coordination networks by the tetrapyridinium spacers. Magnetic studies demonstrate that the magnetic coupling through the double EO azide bridges is ferromagnetic and that through mixed azide/carboxylate bridges is antiferromagnetic. The unprecedented F/AF/AF'/AF'/AF coupling sequence along the chain dictates an uncompensated ground spin state (S = 5/2 per Mn5 unit) and leads to one-dimensional topological ferrimagnetism, which features a minimum in the χT versus T plot.

Dicty_cDB: Contig-U06144-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available pid:none) Homo sapiens infertility-related s... 54 9e-06 AK057482_1( AK057482 |pid:none) Homo sapiens cDNA F... 7e-06 BC149464_1( BC149464 |pid:none) Bos taurus FK506 binding protein l... 54 7e-06 AF311312_1( AF311312 |

Influx of extracellular Zn(2+) into the hippocampal CA1 neurons is required for cognitive performance via long-term potentiation.

Science.gov (United States)

Takeda, A; Suzuki, M; Tempaku, M; Ohashi, K; Tamano, H

2015-09-24

Physiological significance of synaptic Zn(2+) signaling was examined in the CA1 of young rats. In vivo CA1 long-term potentiation (LTP) was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. In vivo CA1 LTP was inhibited under perfusion with CaEDTA and ZnAF-2DA, extracellular and intracellular Zn(2+) chelators, respectively, suggesting that the influx of extracellular Zn(2+) is required for in vivo CA1 LTP induction. The increase in intracellular Zn(2+) was chelated with intracellular ZnAF-2 in the CA1 1h after local injection of ZnAF-2DA into the CA1, suggesting that intracellular Zn(2+) signaling induced during learning is blocked with intracellular ZnAF-2 when the learning was performed 1h after ZnAF-2DA injection. Object recognition was affected when training of object recognition test was performed 1h after ZnAF-2DA injection. These data suggest that intracellular Zn(2+) signaling in the CA1 is required for object recognition memory via LTP. Surprisingly, in vivo CA1 LTP was affected under perfusion with 0.1-1μM ZnCl2, unlike the previous data that in vitro CA1 LTP was enhanced in the presence of 1-5μM ZnCl2. The influx of extracellular Zn(2+) into CA1 pyramidal cells has bidirectional action in CA1 LTP. The present study indicates that the degree of extracellular Zn(2+) influx into CA1 neurons is critical for LTP and cognitive performance. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Thermodynamic study of (alkyl esters+{alpha},{omega}-alkyl dihalides) V. H{sub m}{sup E}andV{sub m}{sup E} for 25 binary mixtures {l_brace}xC{sub u-1}H{sub 2u-1}CO{sub 2}CH{sub 3}+(1-x){alpha},{omega}-ClCH{sub 2}(CH{sub 2}){sub v-2}CH{sub 2}Cl{r_brace}, where u=1 to 5, {alpha}=1 and v={omega}=2 to 6

Energy Technology Data Exchange (ETDEWEB)

Ortega, J. [Laboratorio de Termodinamica y Fisicoquimica de Fluidos, Parque Cientifico-Tecnologico, Campus Universitario de Tafira, Universidad de Las Palmas de Gran Canaria, 35071 Las Palmas de Gran Canaria, Canary Islands (Spain)]. E-mail: jortega@dip.ulpgc.es; Marrero, E. [Laboratorio de Termodinamica y Fisicoquimica de Fluidos, Parque Cientifico-Tecnologico, Campus Universitario de Tafira, Universidad de Las Palmas de Gran Canaria, 35071 Las Palmas de Gran Canaria, Canary Islands (Spain)

2007-05-15

The experimental data of excess molar enthalpies H{sub m}{sup E} and excess molar volumes V{sub m}{sup E} are presented for a set of 25 binary mixtures comprised of the first five methyl esters C{sub u-1}H{sub 2u-1}COOCH{sub 3} (u=1 to 5) and five {alpha},{omega}-dichloroalkanes, ClCH{sub 2}(CH{sub 2}){sub v-2}CH{sub 2}Cl (v=2 to 6), obtained at a temperature of 298.15K and atmospheric pressure. Except for the mixtures with u=1 and v=2 to 6, which are all endothermic and with u=5 and v=2 to 6, which are all exothermic, the others present net endo/exothermic effects and these mixing effects evolve quasiregularly, from endothermic to exothermic, depending on the dichloroalkane present. However, the V{sub m}{sup E} are positive in most mixtures except for those corresponding to u=4,5 and v=5,6, which present contraction effects. These results indicate a set of specific interactions with simultaneous effects for V{sub m}{sup E} of expansion/contraction and for exothermic/endothermic H{sub m}{sup E} for this set of mixtures. The change in V{sub m}{sup E} with the chain length of the compounds is irregular. To achieve a good application of the UNIFAC model using the version of Dang and Tassios, parameters of the ester (G)/dichloride (G') interaction were calculated again, making a distinction, during its application, dependent on the acid part of the ester u. Hence, interaction parameters are presented as a function of u, and of the dichloroalkane chain length v. The most appropriate general expression was of the type:a{sub G/G{sup '}}={phi}(u,v)={sigma}sub(i=0)sup(n)a{sub i-1}u{sup i-1}+{sigma}sub(i=0= )sup(n)b{sub i-1}v{sup i-1}and with this proposal good estimations of enthalpies were obtained with the UNIFAC model.

Sensitivity of MLL-rearranged AML cells to all-trans retinoic acid is associated with the level of H3K4me2 in the RARα promoter region

International Nuclear Information System (INIS)

Sakamoto, K; Imamura, T; Yano, M; Yoshida, H; Fujiki, A; Hirashima, Y; Hosoi, H

2014-01-01

All-trans retinoic acid (ATRA) is well established as differentiation therapy for acute promyelocytic leukemia (APL) in which the PML–RARα (promyelocytic leukemia-retinoic acid receptor α) fusion protein causes blockade of the retinoic acid (RA) pathway; however, in types of acute myeloid leukemia (AML) other than APL, the mechanism of RA pathway inactivation is not fully understood. This study revealed the potential mechanism of high ATRA sensitivity of mixed-lineage leukemia (MLL)-AF9-positive AML compared with MLL-AF4/5q31-positive AML. Treatment with ATRA induced significant myeloid differentiation accompanied by upregulation of RARα, C/EBPα, C/EBPε and PU.1 in MLL-AF9-positive but not in MLL-AF4/5q31-positive cells. Combining ATRA with cytarabine had a synergistic antileukemic effect in MLL-AF9-positive cells in vitro. The level of dimethyl histone H3 lysine 4 (H3K4me2) in the RARα gene-promoter region, PU.1 upstream regulatory region (URE) and RUNX1+24/+25 intronic enhancer was higher in MLL-AF9-positive cells than in MLL-AF4-positive cells, and inhibiting lysine-specific demethylase 1, which acts as a histone demethylase inhibitor, reactivated ATRA sensitivity in MLL-AF4-positive cells. These findings suggest that the level of H3K4me2 in the RARα gene-promoter region, PU.1 URE and RUNX1 intronic enhancer is determined by the MLL-fusion partner. Our findings provide insight into the mechanisms of ATRA sensitivity in AML and novel treatment strategies for ATRA-resistant AML

Dicty_cDB: Contig-U16336-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 90 |pid:none) Thulinius stephaniae clone Thul63f... 42 0.16 CP001325_660( CP00132.... 44 0.055 AF486293_1( AF486293 |pid:none) Giardia intestinalis alpha adaptin... 43 0.072 EU020990_1( EU0209

Påvisning af PCV2

DEFF Research Database (Denmark)

Neumann, Katrine; Buse, Katja Strøm; Hjulsager, Charlotte Kristiane

2018-01-01

Mængden af PCV2-virus i poolede serumprøver kan anvendes til at finde grise med meget PCV2-virus, hvorimod mængden af PCV2-virus i spyt og fæces er velegnede til at vurdere tilstedeværelsen af eller tidspunktet for en begyndende PCV2-infektion...

Påvisning af PCV2

DEFF Research Database (Denmark)

Neumann, Katrine; Buse, Katja Strøm; Hjulsager, Charlotte Kristiane

Mængden af PCV2-virus i poolede serumprøver kan anvendes til at finde grise med meget PCV2-virus, hvorimod mængden af PCV2-virus i spyt og fæces er velegnede til at vurdere tilstedeværelsen af eller tidspunktet for en begyndende PCV2-infektion...

Dicty_cDB: Contig-U14926-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 1426 ) RecName: Full=Actin; &ATAXE(A29877;A54526;S33463) &M16... 340 8e-92 EU128481_1( EU128481 |pid:none) Tanichthys albonube...957_1( AF200957 |pid:none) Rhynchocypris oxycephalus beta-act... 339 2e-91 EU128482_1( EU128482 |pid:none) Tanichthys albonube

Dicty_cDB: Contig-U14689-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available e-137 ( P68541 ) RecName: Full=ATP synthase subunit alpha, mitochondrial... 489 e-137 EU281005_1( EU281005 |pid:none) Hydnora...7705 |pid:none) Orontium aquaticum ATPase alpha su... 486 e-136 AF503356_1( AF503356 |pid:none) Hydnora

Dicty_cDB: Contig-U15667-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 80732 |pid:none) Anabas testudineus cyclin B mRNA, ... 50 3e-04 AF086634_1( AF086...B... 50 3e-04 AM920436_191( AM920436 |pid:none) Penicillium chrysogenum Wisconsi... 50 3e-04 EU780732_1( EU7

Dicty_cDB: Contig-U14029-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 256 7e-67 AF542024_1( AF542024 |pid:none) Griffithsia japonica GTP-binding p... 256 9e-67 AB241242_1( AB241242 |pid:none) Symbiotic... protist of Reticuliterme... 249 7e-65 AB241241_1( AB241241 |pid:none) Symbiotic pro... |pid:none) Plasmodium knowlesi strain H chr... 239 9e-62 AB241243_1( AB241243 |pid:none) Symbiotic

Effekt evaluering af Svangre-Føde Journal i Region Nordjylland

DEFF Research Database (Denmark)

Barlach, Anders

Formål: Evalueringen beskæftiger sig med effekt data opsamlet under anvendelse af den eksisterende papir journal og CSC Clinical Suite Svangre-føde Journal hos de gravide der mødte frem på fødegangen på Ålborg Sygehus før og under pilot implementeringen i maj 2011, og på fødegangen Hjørring Sygehus...... specifikationer og prototyper der også tager stilling til en organiseringen af målinger med henblik på evaluering. Den teoretiske gennemgang efterfølges af den konkrete fremstilling af måle- og evalueringsdesign af Svangre-føde journalen i Region Nordjylland. Resultaterne er genstand for en statistisk...

Study of infrared emission spectroscopy for the B{sup 1}Δ{sub g}–A{sup 1}Π{sub u} and B{sup ′1}Σ{sub g}{sup +}–A{sup 1}Π{sub u} systems of C{sub 2}

Energy Technology Data Exchange (ETDEWEB)

Chen, Wang, E-mail: sc19321@s.okayama-u.ac.jp, E-mail: okakent@okayama-u.ac.jp, E-mail: pbernath@odu.edu; Kawaguchi, Kentarou, E-mail: sc19321@s.okayama-u.ac.jp, E-mail: okakent@okayama-u.ac.jp, E-mail: pbernath@odu.edu; Tang, Jian, E-mail: jtang@okayama-u.ac.jp [Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, 700-8530, Okayama (Japan); Bernath, Peter F., E-mail: sc19321@s.okayama-u.ac.jp, E-mail: okakent@okayama-u.ac.jp, E-mail: pbernath@odu.edu [Department of Chemistry and Biochemistry, Old Dominion University, 4541 Hampton Boulevard, Norfolk, Virginia 23529-0126 (United States)

2016-02-14

Thirteen bands for the B{sup 1}Δ{sub g}–A{sup 1}Π{sub u} system and eleven bands for the B{sup ′1}Σ{sub g}{sup +}–A{sup 1}Π{sub u} system of C{sub 2} were identified in the Fourier transform infrared emission spectra of hydrocarbon discharges. The B{sup ′1}Σ{sub g}{sup +} v = 4 and the B{sup 1}Δ{sub g} v = 6, 7, and 8 vibrational levels involved in nine bands were studied for the first time. A direct global analysis with Dunham parameters was carried out satisfactorily for the B{sup 1}Δ{sub g}–A{sup 1}Π{sub u} system except for a small perturbation in the B{sup 1}Δ{sub g} v = 6 level. The calculated rovibrational term energies up to B{sup 1}Δ{sub g} v = 12 showed that the level crossing between the B{sup 1}Δ{sub g} and d{sup 3}Π{sub g} states is responsible for many of the prominent perturbations in the Swan system observed previously. Nineteen forbidden transitions of the B{sup 1}Δ{sub g}–a{sup 3}Π{sub u} transition were identified and the off-diagonal spin-orbit interaction constant A{sub dB} between d{sup 3}Π{sub g} and B{sup 1}Δ{sub g} was derived as 8.3(1) cm{sup −1}. For the B{sup ′1}Σ{sub g}{sup +}–A{sup 1}Π{sub u} system, only individual band analyses for each vibrational level in the B′{sup 1}Σ{sub g}{sup +} state could be done satisfactorily and Dunham parameters obtained from these effective parameters showed that the anharmonic vibrational constant ω{sub e}x{sub e} is anomalously small (nearly zero). Inspection of the RKR (Rydberg-Klein-Rees) potential curves for the B{sup ′1}Σ{sub g}{sup +} and X{sup 1}Σ{sub g}{sup +} states revealed that an avoided crossing or nearly avoided crossing may occur around 30 000 cm{sup −1}, which is responsible for the anomalous molecular constants in these two states.

Field-aligned current signatures in the near-tail region. 2. Coupling between the region 1 and region 2 systems

International Nuclear Information System (INIS)

Ohtani, S.; Kokubun, S.; Nakamura, R.; Elphic, R.C.; Russell, C.T.; Baker, D.N.

1990-01-01

The development of the substorm-associated current system in the near-tail region is examined in the light of both experiment and theory. First, the March 28, 1979, event is examined intensively by using ground magnetometer data and satellite magnetic field and energetic particle data. The comparison of field-aligned current signatures at geosynchronous altitude and in the near-tail region indicates that the development of the region 1 system is not merely the enhancement in current intensity of the pre-existing system. This finding is consistent with the so-called current wedge model, in which the tail current is converted into a pair of field-aligned currents with the region 1 polarity at substorm onsets. Detailed inspection, however, suggests that the region 2 system is as important as the region 1 system. Statistical properties of the azimuthal magnetic component at synchronous orbit indicate that the deviation during disturbed periods is larger than expected from the enhancement of the region 1 current. These individual and statistical studies suggest that the region 2 system tends to develop in the synchronous region and that the coupling between the region 1 and the region 2 systems is important. The current closure in the magnetosphere is discussed from a viewpoint of the macroscopic behavior of plasma. It is suggested that the dawnside and the duskside region 2 currents are closed in the magnetosphere by the curvature current during the growth phase and by the magnetic gradient current during the expansion phase. The field-aligned currents of the region 1 and the region 2 systems are closed in the ionosphere by the Pedersen current. Consequently, the energy is dissipated as the Joule heating and this energy must be supplied from the magnetosphere. Therefore, the counter part of the Pedersen current, which closes the region 1 and the region 2 currents in magnetosphere, must be the dynamo current

Low-temperature structural transition in the quasi-one-dimensional spin-1/2 compound L i2C u2O (SO4) 2

Science.gov (United States)

Rousse, G.; Rodríguez-Carvajal, J.; Giacobbe, C.; Sun, M.; Vaccarelli, O.; Radtke, G.

2017-04-01

A thorough structural exploration has been made on the quasi-one-dimensional S =1 /2 compound L i2C u2O (SO4) 2 by neutron and synchrotron x-ray diffraction. It reveals the occurrence of a structural transition at 125 K, characterized by a lowering of symmetry from P 42/m to P 1 ¯ , which is possibly driven by an exchange striction mechanism. This transition involves a dimerization of some Cu in the edge-sharing tetrahedral Cu chains. A symmetry mode analysis indicates that one representation, Γ3+Γ4+ , dominates the structural transition. Interestingly, no intermediate structure with P 112 /m symmetry is observed experimentally. Lastly, temperature dependent magnetic susceptibility measurements and neutron diffraction reveal that the magnetic ground state of this compound is a spin-singlet with a spin gap, characterized by the absence of long-range magnetic order down to 1.7 K.

Exploring the supersymmetric U(1 ) B -L×U(1 ) R model with dark matter, muon g - 2 , and Z' mass limits

Science.gov (United States)

Frank, Mariana; Özdal, Özer

2018-01-01

We study the low scale predictions of the supersymmetric standard model extended by U (1 )B -L×U (1 )R symmetry, obtained from S O (10 ) breaking via a left-right supersymmetric model, imposing universal boundary conditions. Two singlet Higgs fields are responsible for the radiative U (1 )B -L×U (1 )R symmetry breaking, and a singlet fermion S is introduced to generate neutrino masses through an inverse seesaw mechanism. The lightest neutralino or sneutrino emerge as dark matter candidates, with different low scale implications. We find that the composition of the neutralino lightest supersymmetric particle (LSP) changes considerably depending on the neutralino LSP mass, from roughly half U (1 )R bino, half minimal supersymmetric model (MSSM) bino, to a singlet higgsino, or completely dominated by the MSSM higgsino. The sneutrino LSP is statistically much less likely, and when it occurs it is a 50-50 mixture of right-handed sneutrino and the scalar S ˜. Most of the solutions consistent with the relic density constraint survive the XENON 1T exclusion curve for both LSP cases. We compare the two scenarios and investigate parameter space points and find consistency with the muon anomalous magnetic moment only at the edge of a 2 σ deviation from the measured value. However, we find that the sneutrino LSP solutions could be ruled out completely by the strict reinforcement of the recent Z' mass bounds. We finally discuss collider prospects for testing the model.

Mild hydrothermal crystal growth of new uranium(IV) fluorides, Na3.13Mg1.43U6F30 and Na2.50Mn1.75U6F30: Structures, optical and magnetic properties

Science.gov (United States)

Yeon, Jeongho; Smith, Mark D.; Tapp, Joshua; Möller, Angela; zur Loye, Hans-Conrad

2016-04-01

Two new uranium(IV) fluorides, Na3.13Mg1.43U6F30 (1) and Na2.50Mn1.75U6F30 (2), were synthesized through an in situ mild hydrothermal route, and were structurally characterized by single crystal X-ray diffraction. The compounds exhibit complex crystal structures composed of corner- or edge-shared UF9 and MF6 (M=Mg, Mn) polyhedra, forming hexagonal channels in the three-dimensional framework, in which ordered or disordered divalent metal and sodium atoms reside. The large hexagonal voids contain the nearly regular M(II)F6 octahedra and sodium ions, whereas the small hexagonal cavities include M(II) and sodium ions on a mixed-occupied site. Magnetic susceptibility measurements yielded effective magnetic moments of 8.36 and 11.6 μB for 1 and 2, respectively, confirming the presence and oxidation states of U(IV) and Mn(II). The large negative Weiss constants indicate the spin gap between a triplet and a singlet state in the U(IV). Magnetization data as a function of applied fields revealed that 2 exhibits paramagnetic behavior due to the nonmagnetic singlet ground state of U(IV) at low temperature. UV-vis diffuse reflectance and X-ray photoelectron spectroscopy data were also analyzed.

11 CFR 105.1 - Place of filing; House candidates and their authorized committees (2 U.S.C. 432(g)(1)).

Science.gov (United States)

2010-01-01

... 11 Federal Elections 1 2010-01-01 2010-01-01 false Place of filing; House candidates and their authorized committees (2 U.S.C. 432(g)(1)). 105.1 Section 105.1 Federal Elections FEDERAL ELECTION COMMISSION GENERAL DOCUMENT FILING (2 U.S.C. 432(g)) § 105.1 Place of filing; House candidates and their authorized...

Effects of miR-33a-5P on ABCA1/G1-mediated cholesterol efflux under inflammatory stress in THP-1 macrophages.

Directory of Open Access Journals (Sweden)

Min Mao

Full Text Available The present study is to investigate whether inflammatory cytokines inhibit ABCA1/ABCG1-mediated cholesterol efflux by regulating miR-33a-5P in THP-1 macrophages. We used interleukin-6 and tumor necrosis factor-alpha in the presence or absence of native low density lipoprotein (LDL to stimulate THP-1 macrophages. THP-1 macrophages were infected by either control lentivirus vectors or lentivirus encoding miR-33a-5P or antisense miR-33a-5P. The effects of inflammatory cytokines, miR-33a-5P and antisense miR-33a-5P on intracellular lipids accumulation and intracellular cholesterol contents were assessed by oil red O staining and quantitative intracellular cholesterol assay. ApoA-I-mediated cholesterol efflux was examined using the fluorescent sterol (BODIPY-cholesterol. The gene and protein expressions of the molecules involved in cholesterol trafficking were examined using quantitative real-time polymerase chain reaction and Western blotting. Inflammatory cytokines or miR-33a-5P increased intracellular lipid accumulation and decreased apoA-I-mediated cholesterol efflux via decreasing the expression of ABCA1 and ABCG1 in the absence or presence of LDL in THP-1 macrophages. However, antisense miR-33a-5P reversed the effects of inflammatory cytokines on intracellular lipid accumulation, cholesterol efflux, and the expression of miR-33a-5P, ABCA1 and ABCG1 in the absence or presence of LDL in THP-1 macrophages. This study indicated that inflammatory cytokines inhibited ABCA1/ABCG1-mediated cholesterol efflux by up-regulating miR-33a-5P in THP-1 macrophages.

Zero Action on Perfect Crystals for U_q(G_2^{(1}

Directory of Open Access Journals (Sweden)

Kailash C. Misra

2010-03-01

Full Text Available The actions of 0-Kashiwara operators on the U_q(G_2^{(1}-crystal B_l in [Yamane S., J. Algebra 210 (1998, 440-486] are made explicit by using a similarity technique from that of a U_q'(D_4^{(3}-crystal. It is shown that {B_l}_{l ≥ 1} forms a coherent family of perfect crystals.

Paramagnetic properties of the (U1-xTbx)Co2Ge2 solid solutions

International Nuclear Information System (INIS)

Kuznietz, Moshe; Pinto, Haim; Ettedgui, Hanania

1995-01-01

Polycrystalline (U 1-x Tb x )Co 2 Ge 2 solid solutions have the ThCr 2 Si 2 -type crystal structure and order antiferromagnetically. AC-susceptibility at 80-295 K yields paramagnetic Curie temperatures θ=-350±50, -15±5, -50±15, -12±5, and -80±5 K, and effective magnetic moments μ eff =4.5, 5.9, 7.3, 8.5, and 12.0 (±0.5)μ B , for samples with x=0, 0.25, 0.50, 0.75 and 1, respectively. The high μ eff values are related to occurrence of paramagnetic moments on U, Tb and Co, of which only U and Tb moments order magnetically. ((orig.))

Dicty_cDB: Contig-U01734-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available ementina cDNA 5'... 32 4.4 2 ( DQ988057 ) Sepia pharaonis GofC1 16S ribosomal RNA gene, par... 32 4.6 2 ( DQ180983 ) Idiopteron bipla...giatum voucher UPOL 000M44 large ... 32 4.6 2 ( AF466309

Activation of liver X receptor decreases atherosclerosis in Ldlr⁻/⁻ mice in the absence of ATP-binding cassette transporters A1 and G1 in myeloid cells.

Science.gov (United States)

Kappus, Mojdeh S; Murphy, Andrew J; Abramowicz, Sandra; Ntonga, Vusisizwe; Welch, Carrie L; Tall, Alan R; Westerterp, Marit

2014-02-01

Liver X receptor (LXR) activators decrease atherosclerosis in mice. LXR activators (1) directly upregulate genes involved in reverse cholesterol transport and (2) exert anti-inflammatory effects mediated by transrepression of nuclear factor-κB target genes. We investigated whether myeloid cell deficiency of ATP-binding cassette transporters A1 and G1 (ABCA1/G1), principal targets of LXR that promote macrophage cholesterol efflux and initiate reverse cholesterol transport, would abolish the beneficial effects of LXR activation on atherosclerosis. LXR activator T0901317 substantially reduced inflammatory gene expression in macrophages lacking ABCA1/G1. Ldlr(-/-) mice were transplanted with Abca1(-/-)Abcg1(-/-) or wild-type bone marrow (BM) and fed a Western-type diet for 6 weeks with or without T0901317 supplementation. Abca1/g1 BM deficiency increased atherosclerotic lesion complexity and inflammatory cell infiltration into the adventitia and myocardium. T0901317 markedly decreased lesion area, complexity, and inflammatory cell infiltration in the Abca1(-/-)Abcg1(-/-) BM-transplanted mice. To investigate whether this was because of macrophage Abca1/g1 deficiency, Ldlr(-/-) mice were transplanted with LysmCreAbca1(fl/fl)Abcg1(fl/fl) or Abca1(fl/fl)Abcg1(fl/fl) BM and fed Western-type diet with or without the more specific LXR agonist GW3965 for 12 weeks. GW3965 decreased lesion size in both groups, and the decrease was more prominent in the LysmCreAbca1(fl/fl)Abcg1(fl/fl) group. The results suggest that anti-inflammatory effects of LXR activators are of key importance to their antiatherosclerotic effects in vivo independent of cholesterol efflux pathways mediated by macrophage ABCA1/G1. This has implications for the development of LXR activators that lack adverse effects on lipogenic genes while maintaining the ability to transrepress inflammatory genes.

Dicty_cDB: Contig-U04090-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 2e-38 AB241243_1( AB241243 |pid:none) Symbiotic protist of Reticuliterme... 162 2...1( CR932504 |pid:none) Paramecium tetraurelia, Small GTPa... 159 8e-38 AB241242_1( AB241242 |pid:none) Symbiotic...romosome 3 ... 156 7e-37 AB241241_1( AB241241 |pid:none) Symbiotic protist of Reticuliterme... 156 7e-37 AF0..... 156 7e-37 AB241245_1( AB241245 |pid:none) Symbiotic protist of Reticuliterme... 156 9e-37 BT038097_1( BT0

Expression and function of Kv1.1 potassium channels in human atria from patients with atrial fibrillation.

Science.gov (United States)

Glasscock, Edward; Voigt, Niels; McCauley, Mark D; Sun, Qiang; Li, Na; Chiang, David Y; Zhou, Xiao-Bo; Molina, Cristina E; Thomas, Dierk; Schmidt, Constanze; Skapura, Darlene G; Noebels, Jeffrey L; Dobrev, Dobromir; Wehrens, Xander H T

2015-09-01

Voltage-gated Kv1.1 channels encoded by the Kcna1 gene are traditionally regarded as being neural-specific with no known expression or intrinsic functional role in the heart. However, recent studies in mice reveal low-level Kv1.1 expression in heart and cardiac abnormalities associated with Kv1.1-deficiency suggesting that the channel may have a previously unrecognized cardiac role. Therefore, this study tests the hypothesis that Kv1.1 channels are associated with arrhythmogenesis and contribute to intrinsic cardiac function. In intra-atrial burst pacing experiments, Kcna1-null mice exhibited increased susceptibility to atrial fibrillation (AF). The atria of Kcna1-null mice showed minimal Kv1 family ion channel remodeling and fibrosis as measured by qRT-PCR and Masson's trichrome histology, respectively. Using RT-PCR, immunocytochemistry, and immunoblotting, KCNA1 mRNA and protein were detected in isolated mouse cardiomyocytes and human atria for the first time. Patients with chronic AF (cAF) showed no changes in KCNA1 mRNA levels relative to controls; however, they exhibited increases in atrial Kv1.1 protein levels, not seen in paroxysmal AF patients. Patch-clamp recordings of isolated human atrial myocytes revealed significant dendrotoxin-K (DTX-K)-sensitive outward current components that were significantly increased in cAF patients, reflecting a contribution by Kv1.1 channels. The concomitant increases in Kv1.1 protein and DTX-K-sensitive currents in atria of cAF patients suggest that the channel contributes to the pathological mechanisms of persistent AF. These findings provide evidence of an intrinsic cardiac role of Kv1.1 channels and indicate that they may contribute to atrial repolarization and AF susceptibility.

Dicty_cDB: Contig-U12744-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available i voucher ufs ... 105 1e-21 AY310255_1( AY310255 |pid:none) Docodesmus trinidadensis voucher...4173 |pid:none) Leptofauchea chiloensis elongation... 96 1e-18 EF033524_1( EF033524 |pid:none) Balbiania investiens...AY391422_1( AY391422 |pid:none) Danio rerio eukaryotic translation... 93 7e-18 BC089730_1( BC089730 |pid:none) Xenopus tropical...e-20 FM992689_285( FM992689 |pid:none) Candida dubliniensis CD36 chromo... 102 1e-20 AF240835_1( AF240835 |p...ia uvarioides elongation... 96 7e-19 DQ357217_1( DQ357217 |pid:none) Leishmania braziliensi

Norepinephrine-Induced Adrenergic Activation Strikingly Increased the Atrial Fibrillation Duration through β1- and α1-Adrenergic Receptor-Mediated Signaling in Mice.

Directory of Open Access Journals (Sweden)

Kenji Suita

Full Text Available Atrial fibrillation (AF is the most common arrhythmias among old people. It causes serious long-term health problems affecting the quality of life. It has been suggested that the autonomic nervous system is involved in the onset and maintenance of AF in human. However, investigation of its pathogenesis and potential treatment has been hampered by the lack of suitable AF models in experimental animals.Our aim was to establish a long-lasting AF model in mice. We also investigated the role of adrenergic receptor (AR subtypes, which may be involved in the onset and duration of AF.Trans-esophageal atrial burst pacing in mice could induce AF, as previously shown, but with only a short duration (29.0 ± 8.1 sec. We found that adrenergic activation by intraperitoneal norepinephrine (NE injection strikingly increased the AF duration. It increased the duration to more than 10 minutes, i.e., by more than 20-fold (656.2 ± 104.8 sec; P<0.001. In this model, a prior injection of a specific β1-AR blocker metoprolol and an α1-AR blocker prazosin both significantly attenuated NE-induced elongation of AF. To further explore the mechanisms underlying these receptors' effects on AF, we assessed the SR Ca(2+ leak, a major trigger of AF, and consequent spontaneous SR Ca(2+ release (SCR in atrial myocytes. Consistent with the results of our in-vivo experiments, both metoprolol and prazosin significantly inhibited the NE-induced SR Ca(2+ leak and SCR. These findings suggest that both β1-AR and α1-AR may play important roles in the development of AF.We have established a long-lasting AF model in mice induced by adrenergic activation, which will be valuable in future AF study using experimental animals, such as transgenic mice. We also revealed the important role of β1- and α1-AR-mediated signaling in the development of AF through in-vivo and in-vitro experiments.

Theoretical study of intermolecular energy transfer involving electronically excited molecules: He(1S) + H2(B 1Σ/sub u/+)

International Nuclear Information System (INIS)

Grimes, R.M.

1986-11-01

To further understanding of gas phase collision dynamics involving electronically-excited molecules, a fully quantum mechanical study of He + H 2 (B 1 Σ/sub u/ + ) was undertaken. Iterative natural orbital configuration interaction (CI) calculations were performed to obtain the interaction potential between He and H 2 (B 1 Σ/sub u/ + ). The potential energy surface (PES) is highly anisotropic and has a van der Waals well of about 0.03 eV for C/sub 2v/ approach. Avoided PES crossings occur with He + H 2 (E,F 1 Σ/sub g/ + ) and with He + H 2 (X 1 Σ/sub g/ + ) and cause a local maximum and a deep minimum in the He + H 2 (B 1 Σ/sub u/ + ) PES, respectively. The crossing with He + H 2 (X 1 Σ/sub g/ + ) provides a mechanism for fluorescence quenching. The computed CI energies were combined with previous multi-reference double excitation CI calculations and fit with analytic functions for convenience in scattering calculations. Accurate dipole polarizabilities and quadrupole moment of H 2 (B 1 Σ/sub u/ + ) were computed for use in the multipole expansion, which is the analytic form of the long-range PES. 129 refs., 28 figs., 35 tabs

Evaluering af ordning med psykologbehandling af personer med let til moderat depression

DEFF Research Database (Denmark)

Fjeldsted, Rita; Christensen, Kaj Sparle

Herværende rapport evaluerer den pr. 1.4.2008 indførte ordning med mulighed for henvisning til psykologbehandling med 60 % tilskud for patienter med let til moderat depression. Evalueringen har betjent sig af flere gensidigt supplerende metoder: spørgeskemaundersøgelser overfor patienter, psykolo......Herværende rapport evaluerer den pr. 1.4.2008 indførte ordning med mulighed for henvisning til psykologbehandling med 60 % tilskud for patienter med let til moderat depression. Evalueringen har betjent sig af flere gensidigt supplerende metoder: spørgeskemaundersøgelser overfor patienter...... tidligere evaluering af forsøgsordning af psykologbehandling af depression i perioden 2005-06. 18.419 personer i alderen 18-37 år blev henvist til psykolog i den undersøgte ordning i perioden 1.2.2009 – 31.1.2010, svarende til en henvisningshyppighed på 1,6 % af baggrundsbefolkningen i samme aldersgruppe....... Ordningen giver mulighed for én rehenvisning, og 9 % blev rehenvist i perioden. Spørgeskemaresultater viser, at kun 33 % af de henviste falder ind under henvisningskriteriet ” let til moderat depression” på tidspunktet for opstart af psykologbehandling, 39 % har ingen tegn på depression, og 28 % har svær...

Missile Liquid Propellant Systems Maintenance. AFS 445X1.

Science.gov (United States)

1981-06-01

4 bf~~ II It - S .. Ui0 j lt 1 1 I I . ,. 1111 ,w I,,,Q , . S0 111 S01111 1 1 60 1 I ’m 041 w0 UI I It I 45w IV taZ& 󈨔 4140 A, : :wt xi Z Z 1 ww .1...0 6 0 a 0- Jewe ~ l .8 2~ I- sca4 a - 0 I,01 04 ~ ~ ~ P .A0 3~ W 40 * 2 U £ WIa -00 1 t - 0 a* d . 0 ~ 4 A- aiSI so a-- r.a 0W 01 P - At0 i4 Im a-I

Mild hydrothermal crystal growth of new uranium(IV) fluorides, Na{sub 3.13}Mg{sub 1.43}U{sub 6}F{sub 30} and Na{sub 2.50}Mn{sub 1.75}U{sub 6}F{sub 30}: Structures, optical and magnetic properties

Energy Technology Data Exchange (ETDEWEB)

Yeon, Jeongho; Smith, Mark D. [Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208 (United States); Tapp, Joshua; Möller, Angela [Department of Chemistry and Texas Center for Superconductivity, University of Houston, Houston, TX 77204 (United States); Loye, Hans-Conrad zur, E-mail: zurloye@mailbox.sc.edu [Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208 (United States)

2016-04-15

Two new uranium(IV) fluorides, Na{sub 3.13}Mg{sub 1.43}U{sub 6}F{sub 30} (1) and Na{sub 2.50}Mn{sub 1.75}U{sub 6}F{sub 30} (2), were synthesized through an in situ mild hydrothermal route, and were structurally characterized by single crystal X-ray diffraction. The compounds exhibit complex crystal structures composed of corner- or edge-shared UF{sub 9} and MF{sub 6} (M=Mg, Mn) polyhedra, forming hexagonal channels in the three-dimensional framework, in which ordered or disordered divalent metal and sodium atoms reside. The large hexagonal voids contain the nearly regular M(II)F{sub 6} octahedra and sodium ions, whereas the small hexagonal cavities include M(II) and sodium ions on a mixed-occupied site. Magnetic susceptibility measurements yielded effective magnetic moments of 8.36 and 11.6 µ{sub B} for 1 and 2, respectively, confirming the presence and oxidation states of U(IV) and Mn(II). The large negative Weiss constants indicate the spin gap between a triplet and a singlet state in the U(IV). Magnetization data as a function of applied fields revealed that 2 exhibits paramagnetic behavior due to the nonmagnetic singlet ground state of U(IV) at low temperature. UV–vis diffuse reflectance and X-ray photoelectron spectroscopy data were also analyzed. - Graphical abstract: Two new quaternary U(IV) fluorides, Na{sub 3.13}Mg{sub 1.43}U{sub 6}F{sub 30} and Na{sub 2.50}Mn{sub 1.75}U{sub 6}F{sub 30}, were crystallized via an in situ reduction step of U(VI) to U(IV) under mild hydrothermal conditions. The compounds show complex crystal structures based on the 3-D building block of U{sub 6}F{sub 30}. Magnetic property measurements revealed that the U(IV) exhibits a nonmagnetic singlet ground state at low temperature with a spin gap. - Highlights: • Na{sub 3.13}Mg{sub 1.43}U{sub 6}F{sub 30} and Na{sub 2.50}Mn{sub 1.75}U{sub 6}F{sub 30} have been synthesized and characterized. • The U(IV) fluorides exhibit complex three-dimensional crystal structures. • The

6 belysninger af vejledning

DEFF Research Database (Denmark)

Toft, Helle Mary; Jessing, Carla Tønder; Nymann, Anette

Artiklerne belyser vejledning af unge og vejledning af voksne. I relation til unge drejer det sig om: 1. vejledning af unge med vanskeligheder i forhold til uddannelse - her unge med særlige vejledningsbehov, og mentorordninger for unge, og 2. vejledning af unge i ungdomsuddannelser og i erhvervs...

Dicty_cDB: Contig-U02523-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available lorococcus marinus str. NATL2A, complete gen... 48 0.82 1 ( AF211148 ) Carsonella ruddii natural-host Russelliana interm...:none) Leishmania major strain Friedlin... 75 4e-12 CP000384_4494( CP000384 |pid:none) Mycobacterium sp. MCS, compl...elaginella moellendorffii mixe... 34 0.16 2 ( GD178393 ) EST04602 Watermelon fruit normalization and subtr...... 50 0.21 1 ( EJ643566 ) 1093012125502 Global-Ocean-Sampling_GS-29-01-01-1... 34 ...e, co... 48 0.82 1 ( EK325308 ) 1095467004903 Global-Ocean-Sampling_GS-31-01-01-1

Identification of Tumor Antigen AF20 as Glycosylated Transferrin Receptor 1 in Complex with Heat Shock Protein 90 and/or Transporting ATPase.

Directory of Open Access Journals (Sweden)

Jason M Shapiro

Full Text Available We previously isolated AF20, a murine monoclonal antibody that recognizes a cell surface glycoprotein of approximately 90-110 kDa. The AF20 antigen is specifically expressed in human hepatoma and colon cancer cell lines, and thus could serve as a cancer biomarker. To uncover the molecular identity of the AF20 antigen, a combination of ion-exchange chromatography, immunoprecipitation, and SDS-polyacrylamide gel electrophoresis was employed to purify the AF20 antigen followed by trypsin digestion and mass spectrometry. Surprisingly, three host proteins were thus purified from human hepatoma and colon cancer cell lines: transferrin receptor 1 (TFR1, heat shock protein 90 (HSP90, and Na+/K+ ATPase or Mg++ ATPase. Co-immunoprecipitation followed by Western blot analysis confirmed interaction among the three proteins. However, only the cDNA encoding TFR1 conferred strong cell surface staining by the AF20 antibody following its transient transfection into a cell line lacking endogenous AF20. In support of the molecular identity of AF20 as TFR1, diferric but not iron-free transferrin could prevent AF20 antigen-antibody interaction during immunoprecipitation. Moreover, very similar patterns of AF20 and TFR1 overexpression was documented in colon cancer tissues. In conclusion, AF20 is glycosylated TFR1. This finding could explain the molecular structure of AF20, its cell surface localization, as well as overexpression in cancer cells. Glycosylated TFR1 should serve as a usefulness target for anti-cancer therapy, or a vehicle for delivery of anti-tumor drugs with high affinity and specificity. The biological significance of the complex formation between TFR1, HSP90, and/or transporting ATPase warrants further investigation.

U.S. Forest Service Region 1 Lake Chemistry, NADP, and IMPROVE air quality data analysis

Science.gov (United States)

Jill Grenon; Mark Story

2009-01-01

This report was developed to address the need for comprehensive analysis of U.S. Forest Service (USFS) Region 1 air quality monitoring data. The monitoring data includes Phase 3 (long-term data) lakes, National Atmospheric Deposition Program (NADP), and Interagency Monitoring of Protected Visual Environments (IMPROVE). Annual and seasonal data for the periods of record...

Metabolic Interactions of Purine Derivatives with Human ABC Transporter ABCG2: Genetic Testing to Assess Gout Risk.

Science.gov (United States)

Ishikawa, Toshihisa; Aw, Wanping; Kaneko, Kiyoko

2013-11-04

In mammals, excess purine nucleosides are removed from the body by breakdown in the liver and excretion from the kidneys. Uric acid is the end product of purine metabolism in humans. Two-thirds of uric acid in the human body is normally excreted through the kidney, whereas one-third undergoes uricolysis (decomposition of uric acid) in the gut. Elevated serum uric acid levels result in gout and could be a risk factor for cardiovascular disease and diabetes. Recent studies have shown that human ATP-binding cassette transporter ABCG2 plays a role of renal excretion of uric acid. Two non-synonymous single nucleotide polymorphisms (SNPs), i.e., 421C>A (major) and 376C>T (minor), in the ABCG2 gene result in impaired transport activity, owing to ubiquitination-mediated proteosomal degradation and truncation of ABCG2, respectively. These genetic polymorphisms are associated with hyperuricemia and gout. Allele frequencies of those SNPs are significantly higher in Asian populations than they are in African and Caucasian populations. A rapid and isothermal genotyping method has been developed to detect the SNP 421C>A, where one drop of peripheral blood is sufficient for the detection. Development of simple genotyping methods would serve to improve prevention and early therapeutic intervention for high-risk individuals in personalized healthcare.

Overweight and obesity in patients with atrial fibrillation: Sex differences in 1-year outcomes in the EORP-AF General Pilot Registry.

Science.gov (United States)

Boriani, Giuseppe; Laroche, Cécile; Diemberger, Igor; Fantecchi, Elisa; Meeder, Joan; Kurpesa, Malgorzata; Baluta, Monica Mariana; Proietti, Marco; Tavazzi, Luigi; Maggioni, Aldo P; Lip, Gregory Y H

2018-04-01

The impact of overweight and obesity on outcomes in "real world" patients with atrial fibrillation (AF) is not fully defined. Second, sex differences in AF outcomes may also exist. The aim was to investigate outcomes at 1 year follow-up for AF patients enrolled in the EORP-AF Registry, according to BMI (kg/m 2 ), comparing patients with normal BMI (18.5 to obesity (≥ 30 kg/m 2 ), in relation to sex differences. Among 2,540 EORP AF patients (38.9% female; median age 69) with 1 year follow-up data available, 720 (28.3%) had a normal BMI, 1,084 (42.7%) were overweight, and 736 (29.0%) were obese. Obese patients were younger and with more prevalent diabetes mellitus and hypertension (P different according to BMI among female patients (9.3% normal BMI, 5.3% overweight, and 4.3 % obese, P = 0.023), but not among male patients (P = 0.748). The composite outcome of thromboembolic events and death was also significantly different, being lower in obese females (P = 0.035). Among male patients, bleeding events were significantly more frequent in obese subjects (P = 0.035). On multivariable Cox analysis, BMI was not independently associated with all-cause mortality. Among AF patients, overweight and obesity are common and associated with better outcomes in females (a finding previously reported as "obesity paradox"), while no significant differences in outcomes are detected among male patients. Final multivariable model found that increasing BMI was not associated with increased risk of all-cause death; conversely, age and comorbidities persisted as major determinants. © 2018 Wiley Periodicals, Inc.

Biomarker screening of oral cancer cell lines revealed sub-populations of CD133-, CD44-, CD24- and ALDH1- positive cancer stem cells

Directory of Open Access Journals (Sweden)

Kendall K

2013-05-01

Full Text Available Head and neck squamous cell carcinoma (HNSCC ranks sixth worldwide for cancer-related mortality. For the past several decades the mainstay of treatment for HNSCC has been surgery and external beam radiation, although more recent trials combining chemotherapy and radiation have demonstrated improvements. However, cancer recurrence and treatment failures continue to occur in a significant percentage of patients. Recent advances in tumor biology have led to the discovery that many cancers, including HNSCC, may contain subpopulations of cells with stem cell-like properties that may explain relapse and recurrence. The objective of this study was to screen existing oral cancer cell lines for biomarkers specific for cells with stem cell-like properties. RNA was isolated for RT-PCR screening using primers for specific mRNA of the biomarkers: CD44, CD24, CD133, NANOG, Nestin, ALDH1, and ABCG2 in CAL27, SCC25 and SCC15 cells. This analysis revealed that some oral cancer cell lines (CAL27 and SCC25 may contain small subpopulations of adhesion- and contact-independent cells (AiDC that also express tumor stem cell markers, including CD44, CD133, and CD24. In addition, CAL27 cells also expressed the intracellular tumor stem cell markers, ALDH1 and ABCG2. Isolation and culture of the adhesion- and contact-independent cells from CAL27 and SCC25 populations revealed differential proliferation rates and more robust inhibition by the MEK inhibitor PD98059, as well as the chemotherapeutic agents Cisplatin and Paclitaxel, within the AiDC CAL27 cells. At least one oral cancer cell line (CAL27 contained subpopulations of cells that express specific biomarkers associated with tumor stem cells which were morphologically and phenotypically distinct from other cells within this cell line.

In vivo binding, pharmacokinetics and metabolism of the selective M2 muscarinic antagonists [3H]AF-DX 116 and [3H]AF-DX 384 in the anesthetized rat

International Nuclear Information System (INIS)

Mickala, Patrick; Boutin, Herve; Bellanger, Cecile; Chevalier, Cyril; MacKenzie, Eric T.; Dauphin, Francois

1996-01-01

The pharmacokinetics, in vivo binding and metabolism of two M 2 muscarinic receptor antagonists, [ 3 H]AF-DX 116 and [ 3 H]AF-DX 384, were studied in anesthetized rats, which received either the tracer alone or following a saturating injection of atropine. Both radioligands were cleared from the circulation with distribution half-lives of 17 and 14 sec and elimination half-lives of 17 and 40 min for [ 3 H]AF-DX 116 and [ 3 H]AF-DX 384, respectively. A radioactive distribution, predominant in peripheral organs when compared to brain, was found at each time studied after tracer injection. Atropine-displaceable tracer uptake was evidenced at 20-40 min in brain (31%), submandibular glands (26%), spleen (37%) and notably heart (55%) for [ 3 H]AF-DX 116 but only in heart (50%) for [ 3 H]AF-DX 384 at 10-20 min. Regional brain sampling revealed a relatively uniform distribution of [ 3 H]AF-DX 384 and a -45% atropine saturation effect (i.e., specific binding) in the thalamus 20 min after injection. Sequential thin-layer chromatographic studies performed on tissue extracts demonstrated the rapid appearance of labeled metabolites of both radiotracers in brain (but less so in liver) and especially in cardiac tissues, where almost 70% of total radioactivity still corresponded to authentic tracer 40 min after injection. Thus, based on their low blood-brain barrier permeability and the high presence of labeled metabolites in the central nervous system, AF-DX 116 and AF-DX 384 might be more helpful in the study of M 2 muscarinic receptors present in heart rather than brain. Labeled with positron emittors, these M 2 antagonists might be applicable to the pathophysiological study of disease states, such as cardiomyopathies

Evaluation of the regional lung function revealed in radioaerosol scintigram of chronic obstructive pulmonary disease, 1

International Nuclear Information System (INIS)

Suzuki, Teruyasu

1980-01-01

We classified the findings of radioaerosol inhalation scintigrams of patients with various stages of obstructive pulmonary disease (COPD) into 4 grades, according to the extent of peripheral irregularity and central hot spot formation; Stage I represents normal homogeneous distribution, stage II represents peripheral irregularity, stage III represents additional hot spot formation and stage IV represents further regional defect. This aerosol grading criteria was then compared with routine and specific lung function tests. The aerosol grading criterion correlated well with FEV sub(1.0)% which is a good indicator of the severity of COPD. The central hot spot formation correlated well with FEV sub(1.0)% and respiratory resistance (R.p.) determined by the oscillation method, both of which are good indicators of abnormality in central airway resistance. Peripheral irregularity correlated well with: 1) flows at 50%VC and 25%VC in a maximum forced expiratory flow volume curve; 2) closing volume (CV/VC%); 3) delta N 2 %/l in N 2 single washout test; and 4) the regional delay of 133 Xe washout process, all of which are sensitive indicators of small airway disease. It is therefore reasonable to conclude that the radioaerosol scintigram reveals the regional lung function both in terms of airway resistance (R) and compliance (C). This criterion was useful in quantitatively evaluating the regional ventilation distribution of COPD and the therapeutic effect on bronchial asthma. The mechanism of aerosol praticle deposition related to characteristic central hot spot formation accompanied with peripheral irregularity in a radioaerosol scintigram of COPD, needs further exploration concerning the aerodynamic behavior of aerosol particles in the airways both during inspiration and expiration. (author)

Dicty_cDB: Contig-U16150-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 1 ( AF333962 ) Staphylococcus aureus transcription termination f... 56 0.006 1 ( EJ636634 ) 1093000601508 Global-Ocean-Sampli...7e-06 2 ( BI503955 ) BB170032B20H11.5 Bee Brain Normalized/Subtracted ... 48 7e-06 2 ( EJ528186 ) 1092955203016 Global-Ocean-Sampli... 62 9e-05 2 ( EK235668 ) 1095460199019 Global-Ocean-Sampling_GS-31-01-01-1... 54 9e-05 2 ( EF583994 ) Uncultured...ng_GS-27-01-01-1... 62 1e-04 1 ( DC238926 ) Hodotermopsis sjoestedti cDNA clone: MY0813AHsBod... 62 1... ) EST_lsal_evj_798759 lsalevj mixed_tissue_mixed_st... 36 0.001 4 ( EK080244 ) 1092961100325 Global-Ocean-Sampli

S =1/2 ferromagnetic-antiferromagnetic alternating Heisenberg chain in a zinc-verdazyl complex

Science.gov (United States)

Yamaguchi, Hironori; Shinpuku, Yasuhiro; Shimokawa, Tokuro; Iwase, Kenji; Ono, Toshio; Kono, Yohei; Kittaka, Shunichiro; Sakakibara, Toshiro; Hosokoshi, Yuko

2015-02-01

We successfully synthesized the zinc-verdazyl complex [Zn(hfac)2].(o -Py -V ) [hfac = 1,1,1,5,5,5-hexafluoroacetylacetonate; o -Py-V = 3-(2-pyridyl)-1,5-diphenylverdazyl], which is an ideal model compound with an S = 1/2 ferromagnetic-antiferromagnetic alternating Heisenberg chain (F-AF AHC). Ab initio molecular-orbital (MO) calculations indicate that two dominant interactions JF and JAF form the S = 1/2 F-AF AHC in this compound. The magnetic susceptibility and magnetic specific heat of the compound exhibit thermally activated behavior below approximately 1 K. Furthermore, its magnetization curve is observed up to the saturation field and directly indicates a zero-field excitation gap of 0.5 T. These experimental results provide evidence for the existence of a Haldane gap. We successfully explain the results in terms of the S = 1/2 F-AF AHC through quantum Monte Carlo calculations with | JAF/JF|=0.22 . The ab initio MO calculations also indicate a weak AF interchain interaction J' and that the coupled F-AF AHCs form a honeycomb lattice. The J' dependence of the Haldane gap is calculated, and the actual value of J' is determined to be less than 0.01 | JF| .

The U(1)-Higgs model: critical behaviour in the confining-Higgs region

International Nuclear Information System (INIS)

Alonso, J.L.; Azcoiti, V.; Campos, I.; Ciria, J.C.; Cruz, A.; Iniguez, D.; Lesmes, F.; Piedrafita, C.; Rivero, A.; Tarancon, A.; Badoni, D.; Fernandez, L.A.; Munoz Sudupe, A.; Ruiz-Lorenzo, J.J.; Gonzalez-Arroyo, A.; Martinez, P.; Pech, J.; Tellez, P.

1993-01-01

We study numerically the critical properties of the U(1)-Higgs lattice model, with fixed Higgs modulus, in the region of small gauge coupling where the Higgs and confining phases merge. We find evidence for a first-order transition line that ends in a second-order point. By means of a rotation in parameter space we introduce thermodynamic magnitudes and critical exponents in close resemblance with simple models that show analogous critical behaviour. The measured data allow us to fit the critical exponents finding values in agreement with the mean-field prediction. The location of the critical point and the slope of the first-order line are accurately measured. (orig.)

Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta

Energy Technology Data Exchange (ETDEWEB)

He, Rui-Qing; Tang, Xiao-Feng; Zhang, Bao-Li [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Shanghai Institute of Hypertension, Shanghai (China); Li, Xiao-Dong [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Shanghai Institute of Hypertension, Shanghai (China); Hong, Mo-Na [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Shanghai Institute of Hypertension, Shanghai (China); Chen, Qi-Zhi [Shanghai Institute of Hypertension, Shanghai (China); Han, Wei-Qing, E-mail: whan020@gmail.com [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Shanghai Institute of Hypertension, Shanghai (China); Gao, Ping-Jin, E-mail: gaopingjin@sibs.ac.cn [State Key Laboratory of Medical Genetics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (China); Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Shanghai Institute of Hypertension, Shanghai (China)

2016-04-29

Adventitial fibroblasts (AFs) can be activated by angiotensin II (Ang II) and exert pro-fibrotic and pro-inflammatory effects in vascular remodeling. Protease-activated receptor (PAR) 1 and 2 play a significant role in fibrogenic and inflammatory diseases. The present study hypothesized that PAR1 and PAR2 are involved in Ang II-induced AF activation and contribute to adventitial remodeling. We found that direct activation of PAR1 and PAR2 with PAR1-AP and PAR2-AP led to AF activation, including proliferation and differentiation of AFs, extracellular matrix synthesis, as well as production of pro-fibrotic cytokine TGF-β and pro-inflammatory cytokines IL-6 and MCP-1. Furthermore, PAR1 and PAR2 mediated Ang II-induced AF activation, since both PAR1 and PAR2 antagonists inhibited Ang II-induced proliferation, migration, differentiation, extracellular matrix synthesis and production of pro-fibrotic and pro-inflammatory cytokines in AFs. Finally, mechanistic study showed that Ang II, via Ang II type I receptor (AT1R), upregulated both PAR1 and PAR2 expression, and transactivated PAR1 and PAR2, as denoted by internalization of both proteins. In conclusion, our results suggest that PAR1 and PAR2 play a critical role in Ang II-induced AF activation, and this may contribute to adventitia-related pathological changes. - Highlights: • Direct activation of PAR1 and PAR2 led to adventitial fibroblast (AF) activation. • PAR1 and PAR2 antagonists attenuated Ang II-induced AF activation. • Ang II induced the upregulation and transactivation of PAR1/PAR2 in AFs.

Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta

International Nuclear Information System (INIS)

He, Rui-Qing; Tang, Xiao-Feng; Zhang, Bao-Li; Li, Xiao-Dong; Hong, Mo-Na; Chen, Qi-Zhi; Han, Wei-Qing; Gao, Ping-Jin

2016-01-01

Adventitial fibroblasts (AFs) can be activated by angiotensin II (Ang II) and exert pro-fibrotic and pro-inflammatory effects in vascular remodeling. Protease-activated receptor (PAR) 1 and 2 play a significant role in fibrogenic and inflammatory diseases. The present study hypothesized that PAR1 and PAR2 are involved in Ang II-induced AF activation and contribute to adventitial remodeling. We found that direct activation of PAR1 and PAR2 with PAR1-AP and PAR2-AP led to AF activation, including proliferation and differentiation of AFs, extracellular matrix synthesis, as well as production of pro-fibrotic cytokine TGF-β and pro-inflammatory cytokines IL-6 and MCP-1. Furthermore, PAR1 and PAR2 mediated Ang II-induced AF activation, since both PAR1 and PAR2 antagonists inhibited Ang II-induced proliferation, migration, differentiation, extracellular matrix synthesis and production of pro-fibrotic and pro-inflammatory cytokines in AFs. Finally, mechanistic study showed that Ang II, via Ang II type I receptor (AT1R), upregulated both PAR1 and PAR2 expression, and transactivated PAR1 and PAR2, as denoted by internalization of both proteins. In conclusion, our results suggest that PAR1 and PAR2 play a critical role in Ang II-induced AF activation, and this may contribute to adventitia-related pathological changes. - Highlights: • Direct activation of PAR1 and PAR2 led to adventitial fibroblast (AF) activation. • PAR1 and PAR2 antagonists attenuated Ang II-induced AF activation. • Ang II induced the upregulation and transactivation of PAR1/PAR2 in AFs.

Dicty_cDB: Contig-U14298-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available um botulinum Ba4 str. 6... 34 7.0 AF078128_1( AF078128 |pid:none) Plasmodium knowlesi from Malaysia ... 34 7...ne) Plasmodium knowlesi from Malaysia ... 34 7.0 AL844508_86( AL844508 |pid:none)

First-principles study on cubic pyrochlore iridates Y2Ir2O7 and Pr2Ir2O7

International Nuclear Information System (INIS)

Ishii, Fumiyuki; Mizuta, Yo Pierre; Kato, Takehiro; Ozaki, Taisuke; Weng Hongming; Onoda, Shigeki

2015-01-01

Fully relativistic first-principles electronic structure calculations based on a noncollinear local spin density approximation (LSDA) are performed for pyrochlore iridates Y 2 Ir 2 O 7 and Pr 2 Ir 2 O 7 . The all-in, all-out antiferromagnetic (AF) order is stablized by the on-site Coulomb repulsion U > U c in the LSDA+U scheme, with U c ∼ 1.1 eV and 1.3 eV for Y 2 Ir 2 O 7 and Pr 2 Ir 2 O 7 , respectively. AF semimetals with and without Weyl points and then a topologically trivial AF insulator successively appear with further increasing U. For U = 1.3 eV, Y 2 Ir 2 O 7 is a topologically trivial narrow-gap AF insulator having an ordered local magnetic moment ∼0.5μ B /Ir, while Pr 2 Ir 2 O 7 is barely a paramagnetic semimetal with electron and hole concentrations of 0.016/Ir, in overall agreements with experiments. With decreasing oxygen position parameter x describing the trigonal compression of IrO 6 octahedra, Pr 2 Ir 2 O 7 is driven through a non-Fermi-liquid semimetal having only an isolated Fermi point of Γ 8 + , showing a quadratic band touching, to a Z 2 topological insulator. (author)

Effect of Long-Term Dietary Arginyl-Fructose (AF on Hyperglycemia and HbA1c in Diabetic db/db Mice

Directory of Open Access Journals (Sweden)

Kwang-Hyoung Lee

2014-05-01

Full Text Available We have previously reported that Amadori compounds exert anti-diabetic effects by lowering sucrose-induced hyperglycemia in normal Sprague-Dawley rats. In the present study we extended our recent findings to evaluate whether α-glucosidase inhibitor arginyl-fructose (AF lowers blood glucose level in diabetic db/db mice, a genetic model for type 2 diabetes. The db/db mice were randomly assigned to high-carbohydrate diets (66.1% corn starch with and without AF (4% in the diet for 6 weeks. Changes in body weight, blood glucose level, and food intake were measured daily for 42 days. Dietary supplementation of AF resulted in a significant decrease of blood glucose level (p < 0.001 and body weight (p < 0.001. The level of HbA1c, a better indicator of plasma glucose concentration over prolonged periods of time, was also significantly decreased for 6-week period (p < 0.001. Dietary treatment of acarbose® (0.04% in diet, a positive control, also significantly alleviated the level of blood glucose, HbA1c, and body weight. These results indicate that AF Maillard reaction product improves postprandial hyperglycemia by suppressing glucose absorption as well as decreasing HbA1c level.

Antigenicity analysis of human parvovirus B19-VP1u protein in the induction of anti-phospholipid syndrome.

Science.gov (United States)

Lin, Chun-Yu; Chiu, Chun-Ching; Cheng, Ju; Lin, Chia-Yun; Shi, Ya-Fang; Tsai, Chun-Chou; Tzang, Bor-Show; Hsu, Tsai-Ching

2018-01-01

Mounting evidence suggests a connection between human parvovirus B19 (B19) and autoimmune diseases, and especially an association between the B19-VP1 unique region (VP1u) and anti-phospholipid syndrome (APS). However, little is known about the antigenicity of B19-VP1u in the induction of APS-like syndrome. To elucidate the antigenicity of B19-VP1u in the induction of APS, N-terminal truncated B19-VP1u (tVP1u) proteins were prepared to immunize Balb/c mice to generate antibodies against B19-tVP1u proteins. The secreted phospholipase A2 (sPLA2) activities and binding specificity of mice anti-B19-tVP1u antibodies with cardiolipin (CL) and beta-2-glycoprotein I (β2GPI) were evaluated by performing immunoblot, ELISA and absorption experiments. A mice model of passively induced APS was adopted. Although sPLA2 activities were identified in all B19-tVP1u proteins, only amino acid residues 61-227 B19-tVP1u exhibited a higher sPLA2 activity. Autoantibodies against CL and β2GPI exhibited binding activities with all B19-tVP1u proteins. IgG that was purified from mice that had been immunized with amino acid residues 21-227 to 121-227 B19-tVP1u proteins exhibited significantly higher binding activity with CL. IgG that was purified from mice that had been immunized with amino acid residues 21-227, 31-227, 82-227 and 91-227 B19-tVP1u proteins exhibited significantly higher binding activity with β2GPI. Accordingly, significantly higher binding inhibition of CL was detected in the presence of amino acid residues 61-227 and 101-227 B19-tVP1u. Significantly higher binding inhibition of β2GPI was detected in the presence of amino acid residues 21-227, 31-227, 82-227 and 91-227 B19-tVP1u. The mice that received amino acid residues 31-227 or 61-227 anti-tB19-VP1u IgG revealed significant thrombocytopenia and those that received amino acid residues 21-227, 31-227, 61-227, 71-227, 82-227, 91-227, 101-227 or 114-227 anti-tB19-VP1u IgG exhibited significantly prolonged aPTT. These

Synthesis of aryl-1H-1,2,3-triazoles via 1,3-dipolar cycloaddition

Directory of Open Access Journals (Sweden)

Wagner O. Valença

2012-06-01

Full Text Available A series of Aryl-1H-1,2,3-triazoles were prepared from the reaction between aril-azide (1 with 1.5 equiv. of terminal alkynes (2a-o. The reactions carried out at room temperature and in the presence of CuI (10 mol% in acetonitrile. The compounds (3a-o were obtained in moderate-to-good yields (50-94%. In general, not was observed significant inductive effect on the reactivity of the alkynes (2a-f. The alcohol alkynes (2i-k showed moderate yields 50-72%. On the other hand, the reaction with alkyl alkynes (2m,n furnished the compounds (3m and (3n in excellent yields of 89% and 90%, respectively.

Dicty_cDB: Contig-U16093-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U16093-1 gap included 1020 2 4899973 4899063 MINUS 29 31 U16093 7 0 0 0 0 2 ...18 0 0 0 0 0 2 0 Show Contig-U16093-1 Contig ID Contig-U16093-1 Contig update 2004. 6.11 Contig sequence >Contig-U16093-1 (Contig...-U16093-1Q) /CSM_Contig/Contig-U16093-1Q.Seq.d TTTTTTTTTTTTTTTTTAATTTTTTTTTTTCATAAAACTT...AAAATTAAATT Gap gap included Contig length 1020 Chromosome number (1..6, M) 2 Chr...pdate 2004. 6.23 Homology vs CSM-cDNA Query= Contig-U16093-1 (Contig-U16093-1Q) /CSM_Contig/Contig-U16093-1Q

Dicty_cDB: Contig-U16203-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available clone SSJ205. 125 5e-30 2 ( AF506014 ) Human rotavirus A strain RMC100 nonstructural pro... 58 0.001 1 ( CP...071 1 ( L04534 ) Rotavirus non-structural protein (NS35) gene, compl... 52 0.071 1 ( EU708963 ) Feline rotavirus...in B3458 segment 7, complete sequ... 52 0.071 1 ( EF672622 ) Human rotavirus A strain Wi61 non-structural pr...ot... 52 0.071 1 ( EF672601 ) Human rotavirus A strain P non-structural protein... 52 0.071 1 ( EF672594 ) Human rotavirus...e, complete cds. 52 0.071 1 ( AB022770 ) Human rotavirus A mRNA for NSP2, complet

Dissociative properties of 1,1,1,2-tetrafluoroethane obtained by computational chemistry

Science.gov (United States)

Hayashi, Toshio; Ishikawa, Kenji; Sekine, Makoto; Hori, Masaru

2018-06-01

The electronic properties and dissociative channels of the alternative to the CCl2F2 (CFC-12) refrigerant, 1,1,1,2-tetrafluoroethane (HFC-134a) with a low global warming potential (GWP, 1430), were revealed by computational chemistry. The results show that CF3 + and CHF2 + ions are mainly produced by ionization. The CF3CH2 + ion is produced by ion pair formation and by direct ionization in the energy region higher than approximately 15 eV, but also in small amounts by the ionization of the dissociated CF3CH2 radical. This information is useful for etching process engineers in leading-edge semiconductor manufacturing.

CYP1A1, CYP1A2, SULT1A1 AND SULT1E1 ALLELIC POLYMORPHISM IN CASE OF GENITAL ENDOMETRIOSIS

Directory of Open Access Journals (Sweden)

Konstantin Sergeevich Kublinskiy

2016-02-01

Up-to-date molecular and genetic analyses reveal that women predisposed to genital endometriosis possess Allele G and Genotypes AG and GG of the polymorphic option A-4889G of the CYP1A1 gene and Allele A and Genotypes CA and AA of the polymorphic option C-734A of the CYP1A2 gene. The polymorphism of the promoter regions of the SULT1A1 (G-638A and SULT1E1 (C-174T genes is not associated with genital endometriosis in women.

Suppression of multiple bioactivities of interleukin-1 and interleukin-2 production by U937 conditioned medium

International Nuclear Information System (INIS)

Wiblin, R.T.; Edmonds, K.; Ellner, J.J.

1986-01-01

The human macrophage-like cell line U937 spontaneously produces a factor which blocks interleukin-1 (IL-1) activity for mouse thymocytes but not mitosis of T-lymphoblastoid cells. The authors examined the effects of U937 conditioned medium (CM) on other IL-1 activities and on interleukin-2 (IL-2) production. U937 was cultured at 5 x 10 6 /ml in RPMI-1640 at 37 0 C for 5 days. The resulting CM inhibited the mitogenic response of C3H/HeJ mouse thymocytes to an IL-1 standard, with an inhibitory of activity of 6.64 U/ml (1 U = reciprocal dilution producing 50% inhibition of maximal response). Similarly, CM inhibited (10.12 U/ml) the fibroblast stimulation promoter activity of IL-1. The effect of CM on IL-2 production was assessed in a direct assay in which IL-2 production by γ-irradiated (12,000 rads) MLA-144 lymphosarcoma cells was assayed as 3 H-thymidine incorporation in CTLL-20 cells. The suppressive activity of CM was 4.95 U/ml; CM did not interfere with the response of CTLL-20 to IL-2. These studies establish that U937 produces factors with multiple, related biological activities; U937 CM blocks IL-2 dependent (thymocyte mitogenesis) and IL-2 independent (fibroblast proliferation) IL-1 activities and interferes with production of, but not response to, IL-2. U937 is an excellent model to study growth inhibitory properties of mononuclear phagocytes

Modellering af kviksølvs globale spredning - 1. rejsebrev fra Harvard

DEFF Research Database (Denmark)

Sørensen, Anne Lærke; Skov, Henrik; Glasius, Marianne

2008-01-01

Spredning af kviksølv via atmosfæren er et globalt problem. Kviksølv har en lang levetid i atmosfæren og deponerer derfor langt fra den oprindelige kilde. Herefter kan det bioakkumulere, hvilket især sker i den akvatiske fødekæde (figur 1). Gennem bioakkumulationen ender kviksølv i det øverste le...

Dicty_cDB: Contig-U03848-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available 6_443( CR382136 |pid:none) Debaryomyces hansenii strain CBS... 278 6e-73 AY122629_1( AY122629 |pid:none) Cryptobia salmositica...ta strain Ankara... 458 e-127 CP001071_1966( CP001071 |pid:none) Akkermansia muciniphila A...5270_34( CT005270 |pid:none) Leishmania major strain Friedlin,... 317 1e-84 AF384808_1( AF384808 |pid:none) Cryptococcus neoformans...c... 305 6e-81 FM992694_186( FM992694 |pid:none) Candida dubliniensi... AM494970 |pid:none) Leishmania braziliensis chromosom... 205 7e-51 AY651251_1( AY651251 |pid:none) Ichthyobodo neca

Factors predisposing to coma and delirium: fentanyl and midazolam exposure; CYP3A5, ABCB1, and ABCG2 genetic polymorphisms; and inflammatory factors.

Science.gov (United States)

Skrobik, Yoanna; Leger, Caroline; Cossette, Mariève; Michaud, Veronique; Turgeon, Jacques

2013-04-01

Delirium and sedative-induced coma are described as incremental manifestations of cerebral dysfunction. Both may be associated with sedative or opiate doses and pharmacokinetic or pharmacogenetic variables, such as drug plasma levels (exposure), drug metabolism, and/or their transport across the blood-brain barrier. To compare biological and drug treatment characteristics in patients with coma and/or delirium while in the ICU. In 99 patients receiving IV fentanyl, midazolam, or both, we evaluated drug doses, covariates likely to influence drug effects (age, body mass index, and renal and hepatic dysfunction); delirium risk factors; concomitant administration of CYP3A and P-glycoprotein substrates/inhibitors; ABCB1, ABCG2, and CYP3A5 genetic polymorphisms; and fentanyl and midazolam plasma levels. Delirium and coma were evaluated daily. In patients with only coma (n=15), only delirium (n=7), and neither ever (n=14), we measured plasma levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-1RA, IL-6, IL-8, IL-10, IL-17,macrophage inflammatory protein-1β, and monocyte chemotactic protein-1. Time to first coma was associated with fentanyl and midazolam doses (p=0.03 and p=0.01, respectively). The number of days in coma was associated with the number of days of coadministration of CYP3A inhibitors (r=0.30; p=0.006). Plasma levels of fentanyl were higher in patients with clinical coma (3.7±4.7 vs. 2.0±1.8 ng/mL, p=0.0001) as were midazolam plasma levels (1050±2232 vs. 168±249 ng/mL, p=0.0001). Delirium occurrence was unrelated to midazolam administration, cumulative doses, or serum levels. Days with delirium were associated with days of coadministration of P-glycoprotein inhibitor (r=0.35; p=0.0004). Delirious patients had higher levels of the inflammatory mediator IL-6 than comatose patients (129.3 vs. 35.0 pg/mL, p=0.05). Coma is associated with fentanyl and midazolam exposure; delirium is unrelated to midazolam and may be linked to inflammatory status

Dicty_cDB: Contig-U13455-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available Contig-U13455-1 no gap 750 2 945431 946181 PLUS 2 2 U13455 0 0 0 0 0 0 1 0 0 1 0 0 0 0 Show Contig...-U13455-1 Contig ID Contig-U13455-1 Contig update 2002.12.18 Contig sequence >Contig-U13455-1 (Contig...-U13455-1Q) /CSM_Contig/Contig-U13455-1Q.Seq.d TAATTCCAACAACATCAACAAATTCAACAACAATTACAAATGCAACAACA TA...CAATAATAATAATAATAACAATAACAATAATAATAA Gap no gap Contig length 750 Chromosome number (1..6, M) 2 Chromosome l...KMLEYIQKNPSATRPSCIQVVQQPSSKVVWKNRRLDTPFKVKVDLKAASAMA GTNLTTASVITIGIVTDHKGKLQIDSVENFTEAFNGQGLAVFQGLKMTKGTWGKE

Tissue expression pattern of ABCG transporter indicates functional roles in reproduction of Toxocara canis.

Science.gov (United States)