Comparative analysis of Mycobacterium and related Actinomycetes yields insight into the evolution of Mycobacterium tuberculosis pathogenesis.

Science.gov (United States)

McGuire, Abigail Manson; Weiner, Brian; Park, Sang Tae; Wapinski, Ilan; Raman, Sahadevan; Dolganov, Gregory; Peterson, Matthew; Riley, Robert; Zucker, Jeremy; Abeel, Thomas; White, Jared; Sisk, Peter; Stolte, Christian; Koehrsen, Mike; Yamamoto, Robert T; Iacobelli-Martinez, Milena; Kidd, Matthew J; Maer, Andreia M; Schoolnik, Gary K; Regev, Aviv; Galagan, James

2012-03-28

The sequence of the pathogen Mycobacterium tuberculosis (Mtb) strain H37Rv has been available for over a decade, but the biology of the pathogen remains poorly understood. Genome sequences from other Mtb strains and closely related bacteria present an opportunity to apply the power of comparative genomics to understand the evolution of Mtb pathogenesis. We conducted a comparative analysis using 31 genomes from the Tuberculosis Database (TBDB.org), including 8 strains of Mtb and M. bovis, 11 additional Mycobacteria, 4 Corynebacteria, 2 Streptomyces, Rhodococcus jostii RHA1, Nocardia farcinia, Acidothermus cellulolyticus, Rhodobacter sphaeroides, Propionibacterium acnes, and Bifidobacterium longum. Our results highlight the functional importance of lipid metabolism and its regulation, and reveal variation between the evolutionary profiles of genes implicated in saturated and unsaturated fatty acid metabolism. It also suggests that DNA repair and molybdopterin cofactors are important in pathogenic Mycobacteria. By analyzing sequence conservation and gene expression data, we identify nearly 400 conserved noncoding regions. These include 37 predicted promoter regulatory motifs, of which 14 correspond to previously validated motifs, as well as 50 potential noncoding RNAs, of which we experimentally confirm the expression of four. Our analysis of protein evolution highlights gene families that are associated with the adaptation of environmental Mycobacteria to obligate pathogenesis. These families include fatty acid metabolism, DNA repair, and molybdopterin biosynthesis. Our analysis reinforces recent findings suggesting that small noncoding RNAs are more common in Mycobacteria than previously expected. Our data provide a foundation for understanding the genome and biology of Mtb in a comparative context, and are available online and through TBDB.org.

Comparative analysis of mycobacterium and related actinomycetes yields insight into the evolution of mycobacterium tuberculosis pathogenesis

Directory of Open Access Journals (Sweden)

McGuire Abigail

2012-03-01

Full Text Available Abstract Background The sequence of the pathogen Mycobacterium tuberculosis (Mtb strain H37Rv has been available for over a decade, but the biology of the pathogen remains poorly understood. Genome sequences from other Mtb strains and closely related bacteria present an opportunity to apply the power of comparative genomics to understand the evolution of Mtb pathogenesis. We conducted a comparative analysis using 31 genomes from the Tuberculosis Database (TBDB.org, including 8 strains of Mtb and M. bovis, 11 additional Mycobacteria, 4 Corynebacteria, 2 Streptomyces, Rhodococcus jostii RHA1, Nocardia farcinia, Acidothermus cellulolyticus, Rhodobacter sphaeroides, Propionibacterium acnes, and Bifidobacterium longum. Results Our results highlight the functional importance of lipid metabolism and its regulation, and reveal variation between the evolutionary profiles of genes implicated in saturated and unsaturated fatty acid metabolism. It also suggests that DNA repair and molybdopterin cofactors are important in pathogenic Mycobacteria. By analyzing sequence conservation and gene expression data, we identify nearly 400 conserved noncoding regions. These include 37 predicted promoter regulatory motifs, of which 14 correspond to previously validated motifs, as well as 50 potential noncoding RNAs, of which we experimentally confirm the expression of four. Conclusions Our analysis of protein evolution highlights gene families that are associated with the adaptation of environmental Mycobacteria to obligate pathogenesis. These families include fatty acid metabolism, DNA repair, and molybdopterin biosynthesis. Our analysis reinforces recent findings suggesting that small noncoding RNAs are more common in Mycobacteria than previously expected. Our data provide a foundation for understanding the genome and biology of Mtb in a comparative context, and are available online and through TBDB.org.

Main: 1E1E [RPSD[Archive

Lifescience Database Archive (English)

Full Text Available Mays Molecule: Beta-Glucosidase; Chain: A, B; Engineered: Yes Glycoside Hydrolase 3.2.1.21 (Beta-Glucosidas..., B.Henrissat, A.Esen Crystal Structure Of A Monocotyledon (Maize Zmglu1) Beta-Gl...55-566.|PDB; 1E55; X-ray; A/B=55-566.|PDB; 1E56; X-ray; A/B=55-566.|PDB; 1H49; X-ray; A/B=55-566.|PDB; 1HXJ; X-ray; A/B=60-566.|Mai...ze-2DPAGE; P49235; COLEOPTILE.|MaizeDB; 13870; -.|InterPro

The E1 proteins

International Nuclear Information System (INIS)

Bergvall, Monika; Melendy, Thomas; Archambault, Jacques

2013-01-01

E1, an ATP-dependent DNA helicase, is the only enzyme encoded by papillomaviruses (PVs). It is essential for replication and amplification of the viral episome in the nucleus of infected cells. To do so, E1 assembles into a double-hexamer at the viral origin, unwinds DNA at the origin and ahead of the replication fork and interacts with cellular DNA replication factors. Biochemical and structural studies have revealed the assembly pathway of E1 at the origin and how the enzyme unwinds DNA using a spiral escalator mechanism. E1 is tightly regulated in vivo, in particular by post-translational modifications that restrict its accumulation in the nucleus. Here we review how different functional domains of E1 orchestrate viral DNA replication, with an emphasis on their interactions with substrate DNA, host DNA replication factors and modifying enzymes. These studies have made E1 one of the best characterized helicases and provided unique insights on how PVs usurp different host-cell machineries to replicate and amplify their genome in a tightly controlled manner. - Highlights: • The papillomavirus E1 helicase orchestrates replication of the viral DNA genome. • E1 assembles into a double-hexamer at the viral origin with the help of E2. • E1 interacts with cellular DNA replication factors. • E1 unwinds DNA using a spiral escalator mechanism. • Nuclear accumulation of E1 is regulated by post-translational modifications

Structure of a yeast 40S-eIF1-eIF1A-eIF3-eIF3j initiation complex.

Science.gov (United States)

Aylett, Christopher H S; Boehringer, Daniel; Erzberger, Jan P; Schaefer, Tanja; Ban, Nenad

2015-03-01

Eukaryotic translation initiation requires cooperative assembly of a large protein complex at the 40S ribosomal subunit. We have resolved a budding yeast initiation complex by cryo-EM, allowing placement of prior structures of eIF1, eIF1A, eIF3a, eIF3b and eIF3c. Our structure highlights differences in initiation-complex binding to the ribosome compared to that of mammalian eIF3, demonstrates a direct contact between eIF3j and eIF1A and reveals the network of interactions between eIF3 subunits.

Superactive cellulase formulation using cellobiohydrolase-1 from Penicillium funiculosum

Science.gov (United States)

Adney, William S.; Baker, John O.; Decker, Stephen R.; Chou, Yat-Chen; Himmel, Michael E.; Ding, Shi-You

2012-10-09

Purified cellobiohydrolase I (glycosyl hydrolase family 7 (Cel7A)) enzymes from Penicillium funiculosum demonstrate a high level of specific performance in comparison to other Cel7 family member enzymes when formulated with purified EIcd endoglucanase from A. cellulolyticus and tested on pretreated corn stover. This result is true of the purified native enzyme, as well as recombinantly expressed enzyme, for example, that enzyme expressed in a non-native Aspergillus host. In a specific example, the specific performance of the formulation using purified recombinant Cel7A from Penicillium funiculosum expressed in A. awamori is increased by more than 200% when compared to a formulation using purified Cel7A from Trichoderma reesei.

Superactive cellulase formulation using cellobiohydrolase-1 from Penicillium funiculosum

Science.gov (United States)

Adney, William S.; Baker, John O.; Decker, Stephen R.; Chou, Yat-Chen; Himmel, Michael E.; Ding, Shi-You

2008-11-11

Purified cellobiohydrolase I (glycosyl hydrolase family 7 (Cel7A) enzymes from Penicillium funiculosum demonstrate a high level of specific performance in comparison to other Cel7 family member enzymes when formulated with purified EIcd endoglucanase from A. cellulolyticus and tested on pretreated corn stover. This result is true of the purified native enzyme, as well as recombinantly expressed enzyme, for example, that enzyme expressed in a non-native Aspergillus host. In a specific example, the specific performance of the formulation using purified recombinant Cel7A from Penicillium funiculosum expressed in A. awamori is increased by more than 200% when compared to a formulation using purified Cel7A from Trichoderma reesei.

THE E1 PROTEINS

OpenAIRE

Bergvall, Monika; Melendy, Thomas; Archambault, Jacques

2013-01-01

E1, an ATP-dependent DNA helicase, is the only enzyme encoded by papillomaviruses (PVs). It is essential for replication and amplification of the viral episome in the nucleus of infected cells. To do so, E1 assembles into a double-hexamer at the viral origin, unwinds DNA at the origin and ahead of the replication fork and interacts with cellular DNA replication factors. Biochemical and structural studies have revealed the assembly pathway of E1 at the origin and how the enzyme unwinds DNA usi...

Protein phosphatase PPM1G regulates protein translation and cell growth by dephosphorylating 4E binding protein 1 (4E-BP1).

Science.gov (United States)

Liu, Jianyu; Stevens, Payton D; Eshleman, Nichole E; Gao, Tianyan

2013-08-09

Protein translation initiation is a tightly controlled process responding to nutrient availability and mitogen stimulation. Serving as one of the most important negative regulators of protein translation, 4E binding protein 1 (4E-BP1) binds to translation initiation factor 4E and inhibits cap-dependent translation in a phosphorylation-dependent manner. Although it has been demonstrated previously that the phosphorylation of 4E-BP1 is controlled by mammalian target of rapamycin in the mammalian target of rapamycin complex 1, the mechanism underlying the dephosphorylation of 4E-BP1 remains elusive. Here, we report the identification of PPM1G as the phosphatase of 4E-BP1. A coimmunoprecipitation experiment reveals that PPM1G binds to 4E-BP1 in cells and that purified PPM1G dephosphorylates 4E-BP1 in vitro. Knockdown of PPM1G in 293E and colon cancer HCT116 cells results in an increase in the phosphorylation of 4E-BP1 at both the Thr-37/46 and Ser-65 sites. Furthermore, the time course of 4E-BP1 dephosphorylation induced by amino acid starvation or mammalian target of rapamycin inhibition is slowed down significantly in PPM1G knockdown cells. Functionally, the amount of 4E-BP1 bound to the cap-dependent translation initiation complex is decreased when the expression of PPM1G is depleted. As a result, the rate of cap-dependent translation, cell size, and protein content are increased in PPM1G knockdown cells. Taken together, our study has identified protein phosphatase PPM1G as a novel regulator of cap-dependent protein translation by negatively controlling the phosphorylation of 4E-BP1.

In vitro characterization of gE negative bovine herpesvirus types 1.1 (BHV-1.1 and 1.2a (BHV-1.2a Caracterização in vitro de herpes vírus bovino tipos 1.1 (BHV-1.1 e 1.2a (BHV-1.2a gE negativos

Directory of Open Access Journals (Sweden)

Fernando R. Spilki

2004-09-01

Full Text Available This study aimed the in vitro growth characterization of a previously constructed Brazilian bovine herpesvirus 1.2a with a deletion in the glycoprotein E gene (BHV-1.2a gE-. The plaque sizes, penetration and growth kinetics of the Brazilian BHV-1.2a gE- were studied and compared with the parental virus, as well as with a BHV-1.1 gE- recombinant derived from an European BHV-1.1 strain. No statistical differences were observed between the gE- recombinants and the respective parental viruses penetration assays were performed. When single step growth curves were studied, no statistical differences were observed between gE- and parental viruses. However, it was observed that both gE- viruses were excreted from cells in significantly higher titres at 11 hours post infection in comparison with parental viruses. No statistical differences were observed when plaque sizes of parental viruses or gE- viruses we analyzed separately in each cell type. However, both gE- recombinants displayed a significantly reduced plaque areas on three different cell cultures, in comparison with parental viruses, indicating that the lack of gE had the same effect on both BHV-1 subtypes, manifested by a restricted cell-to-cell spread in infected cells.O presente estudo teve como objetivo a caracterização das propriedades de crescimento in vitro de uma amostra brasileira de herpesvírus bovino tipo 1.2a que apresenta uma deleção no gene que codifica a glicoproteína E (BHV-1.2a gE-. Os tamanhos de placa, cinética de penetração e cinética de multiplicação do vírus BHV-1.2a gE- foram estudados e comparados com o vírus parental, bem como com um vírus BHV-1.1 gE- recombinante, o qual é derivado de uma amostra européia de BHV-1.1. Em termos de cinética de penetração, não foram observadas diferenças significativas quando comparados os vírus gE- com os parentais. A determinação da cinética de multiplicação não demonstrou diferenças significativas entre os

Arterial portography using prostaglandin E1

International Nuclear Information System (INIS)

Seo, Heung Suk; Kim, Hyung Sik; Lee, Seung Chul; Lee, Seung Ro; Hahm, Chang Kok; Kim, Jung Jin; Cho, Suk Shin

1987-01-01

A total of 110 arterial portographies via superior mesenteric artery were performed on 100 patients at Hanyang University Hospital in the past 2 years. There were 20 control portographies and 90 portographies using prostaglandin E 1 Twenty μg prostaglandin E 1 was injected for 30 seconds in the superior mesenteric artery 30 seconds before injection of contrast media. Both control and prostaglandin E 1 portograms were evaluated for quality of opacification and side effects of prostaglandin E 1 were recorded. The results were as follows; 1.The appearance time and optimal opacification time of the portal vein system were obtained approximately 6 seconds earlier in the prostaglandin E 1 portograms than in the control portograms. 2.The incidence of opacification of the intrahepatic portal veins was greater in the prostaglandin E 1 portograms than in the control portograms. 3.The main portal vein and intrahepatic portal veins were more clearly opacified in the prostaglandin... portograms than in the control portograms. 4.The prostaglandin E 1 portograms provided clearer and more detailed opacification of the portal vein system than the control portograms in the same patients. 5.There was a minimal decrease in blood pressure with a concomitant small rise in heart rate and mild abdominal pain following the prostaglandin E 1 injection. The authors found arterial portography using prostaglandin E 1 simple, safe and useful for clear and detailed visualization of the portal vein system

Distinct transcriptomic changes in E14.5 mouse skeletal muscle lacking RYR1 or Cav1.1 converge at E18.5

Science.gov (United States)

Henry, Margit; Rotshteyn, Tamara; Brunn, Anna; Carstov, Mariana; Deckert, Martina; Hescheler, Jürgen; Sachinidis, Agapios; Pfitzer, Gabriele

2018-01-01

In skeletal muscle the coordinated actions of two mechanically coupled Ca2+ channels—the 1,4-dihydropyridine receptor (Cav1.1) and the type 1 ryanodine receptor (RYR1)–underlie the molecular mechanism of rapid cytosolic [Ca2+] increase leading to contraction. While both [Ca2+]i and contractile activity have been implicated in the regulation of myogenesis, less is known about potential specific roles of Cav1.1 and RYR1 in skeletal muscle development. In this study, we analyzed the histology and the transcriptomic changes occurring at E14.5 –the end of primary myogenesis and around the onset of intrauterine limb movement, and at E18.5 –the end of secondary myogenesis, in WT, RYR1-/-, and Cav1.1-/- murine limb skeletal muscle. At E14.5 the muscle histology of both mutants exhibited initial alterations, which became much more severe at E18.5. Immunohistological analysis also revealed higher levels of activated caspase-3 in the Cav1.1-/- muscles at E14.5, indicating an increase in apoptosis. With WT littermates as controls, microarray analyses identified 61 and 97 differentially regulated genes (DEGs) at E14.5, and 493 and 1047 DEGs at E18.5, in RYR1-/- and Cav1.1-/- samples, respectively. Gene enrichment analysis detected no overlap in the affected biological processes and pathways in the two mutants at E14.5, whereas at E18.5 there was a significant overlap of DEGs in both mutants, affecting predominantly processes linked to muscle contraction. Moreover, the E18.5 vs. E14.5 comparison revealed multiple genotype-specific DEGs involved in contraction, cell cycle and miRNA-mediated signaling in WT, neuronal and bone development in RYR1-/-, and lipid metabolism in Cav1.1-/- samples. Taken together, our study reveals discrete changes in the global transcriptome occurring in limb skeletal muscle from E14.5 to E18.5 in WT, RYR1-/- and Cav1.1-/- mice. Our results suggest distinct functional roles for RYR1 and Cav1.1 in skeletal primary and secondary myogenesis. PMID

Molecular docking studies of (1E,3E,5E)-1,6-Bis(substituted phenyl)hexa-1,3,5-triene and 1,4-Bis(substituted trans-styryl)benzene analogs as novel tyrosinase inhibitors.

Science.gov (United States)

Ha, Young Mi; Lee, Hye Jin; Park, Daeui; Jeong, Hyoung Oh; Park, Ji Young; Park, Yun Jung; Lee, Kyung Jin; Lee, Ji Yeon; Moon, Hyung Ryong; Chung, Hae Young

2013-01-01

We simulated the docking of the tertiary structure of mushroom tyrosinase with our compounds. From the structure-tyrosinase inhibitory activity relationship, it is notable that compounds 4, 8 and 11 showed similar or better activity rates than kojic acid which was used as a positive control. Compounds 17, 21, and 23 among benzene analogs that possess the same substituent showed significantly lower tyrosinase inhibitory effects. Therefore, we have confirmed that among the compounds showing better tyrosinase inhibitory effects than kojic acid, the compounds with triene analogs have better tyrosinase inhibitory effect than the compounds with benzene analogs. Docking simulation suggested the mechanism of compounds by several key residues which had possible hydrogen bonding interactions. The pharmacophore model underlined the features of active compounds, 4,4'-((1E,3E,5E)-hexa-1,3,5-triene-1,6-diyl)diphenol, 5,5'-((1E,3E,5E)-hexa-1,3,5-triene-1,6-diyl)bis(2-methoxy-phenol), and 5,5'-((1E,3E,5E)-hexa-1,3,5-triene-1,6-diyl)dibenzene-1,3-diol among triene derivatives which had several hydrogen bond groups on both terminal rings. The soundness of the docking results and the agreement with the pharmacophores suggest that it can be conveniently exploited to design inhibitors with an improved affinity for tyrosinase.

6,6'-(1E,1'E-((1R,2R-1,2-Diphenylethane-1,2-diylbis(azan-1-yl-1-ylidenebis(methan-1-yl-1-ylidenebis(2-tert-butyl-4-((trimethylsilylethynylphenol

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David Díaz Díaz

2013-03-01

Full Text Available Functionalizable salen derivative, 6,6'-(1E,1'E-((1R,2R-1,2-diphenylethane-1,2-diylbis(azan-1-yl-1-ylidenebis(methan-1-yl-1-ylidenebis(2-tert-butyl-4-((trimethylsilyl ethyn-ylphenol (3, was synthesized by condensation between (1R,2R-1,2-diphenylethane-1,2-diamine (2 and 3-tert-butyl-2-hydroxy-5-((trimethylsilylethynyl benzaldehyde (1 under refluxing conditions. The title compound was characterized by 1H-NMR, 13C-NMR, FT-IR, high-resolution mass spectrometry, optical rotation and melting point determination.

The Aryl Hydrocarbon Receptor Binds to E2F1 and Inhibits E2F1-induced Apoptosis

Science.gov (United States)

Marlowe, Jennifer L.; Fan, Yunxia; Chang, Xiaoqing; Peng, Li; Knudsen, Erik S.; Xia, Ying

2008-01-01

Cellular stress by DNA damage induces checkpoint kinase-2 (CHK2)-mediated phosphorylation and stabilization of the E2F1 transcription factor, leading to induction of apoptosis by activation of a subset of proapoptotic E2F1 target genes, including Apaf1 and p73. This report characterizes an interaction between the aryl hydrocarbon (Ah) receptor (AHR), a ligand-activated transcription factor, and E2F1 that results in the attenuation of E2F1-mediated apoptosis. In Ahr−/− fibroblasts stably transfected with a doxycycline-regulated AHR expression vector, inhibition of AHR expression causes a significant elevation of oxidative stress, γH2A.X histone phosphorylation, and E2F1-dependent apoptosis, which can be blocked by small interfering RNA-mediated knockdown of E2F1 expression. In contrast, ligand-dependent AHR activation protects these cells from etoposide-induced cell death. In cells expressing both proteins, AHR and E2F1 interact independently of the retinoblastoma protein (RB), because AHR and E2F1 coimmunoprecipitate from extracts of RB-negative cells. Additionally, chromatin immunoprecipitation assays indicate that AHR and E2F1 bind to the Apaf1 promoter at a region containing a consensus E2F1 binding site but no AHR binding sites. AHR activation represses Apaf1 and TAp73 mRNA induction by a constitutively active CHK2 expression vector. Furthermore, AHR overexpression blocks the transcriptional induction of Apaf1 and p73 and the accumulation of sub-G0/G1 cells resulting from ectopic overexpression of E2F1. These results point to a proproliferative, antiapoptotic function of the Ah receptor that likely plays a role in tumor progression. PMID:18524851

26 CFR 1.642(e)-1 - Depreciation and depletion.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Depreciation and depletion. 1.642(e)-1 Section 1... (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.642(e)-1 Depreciation and depletion. An estate or trust is allowed the deductions for depreciation and depletion, but only to the extent the...

Probability 1/e

Science.gov (United States)

Koo, Reginald; Jones, Martin L.

2011-01-01

Quite a number of interesting problems in probability feature an event with probability equal to 1/e. This article discusses three such problems and attempts to explain why this probability occurs with such frequency.

The yields of 1P and 1D resonances in the He(e,2e)He+ reaction

International Nuclear Information System (INIS)

Lhagva, O.; Badamdamdin, R.; Strakhova, S.I.; Hehnmedeh, L.

1991-01-01

In the first Born approximation the dependence of the yields of the 1 P and 1 D resonances in the He(e,2e)He + reaction on the momentum transfer in the recoil peak region at incident energies E 0 =1000 eV is studied. It is shown that in a certain range of the ejection angle and for the large momentum transfer the yield of the 1 D resonance dominates over the 1 P resonance one. 12 refs.; 4 figs

Raman E sub 1 , E sub 1 + DELTA sub 1 resonance in nonstressed quantum dots of germanium

CERN Document Server

Talochkin, A B; Efanov, A V; Kozhemyako, I G; Shumskij, V N

2001-01-01

The Raman light scattering on the optical phonons in the nonstressed Ge quantum dots, obtained in the GaAs/ZnSe/Ge/ZnSe structures is studied through the molecular-beam epitaxy. The E sub 1 , E sub 1 + DELTA sub 1 resonance energy shift, connected with quantization of the electron and hole states spectrum in the quantum dots is observed. Application of the simplest localization model with an account of the Ge electron states spectrum made it possible to explain the observed peculiarities

E4orf1 Limits the Oncolytic Potential of the E1B-55K Deletion Mutant Adenovirus▿

Science.gov (United States)

Thomas, Michael A.; Broughton, Robin S.; Goodrum, Felicia D.; Ornelles, David A.

2009-01-01

Clinical trials have shown oncolytic adenoviruses to be tumor selective with minimal toxicity toward normal tissue. The virus ONYX-015, in which the gene encoding the early region 1B 55-kDa (E1B-55K) protein is deleted, has been most effective when used in combination with either chemotherapy or radiation therapy. Therefore, improving the oncolytic nature of tumor-selective adenoviruses remains an important objective for improving this form of cancer therapy. Cells infected during the G1 phase of the cell cycle with the E1B-55K deletion mutant virus exhibit a reduced rate of viral late protein synthesis, produce fewer viral progeny, and are less efficiently killed than cells infected during the S phase. Here we demonstrate that the G1 restriction imposed on the E1B-55K deletion mutant virus is due to the viral oncogene encoded by open reading frame 1 of early region 4 (E4orf1). E4orf1 has been reported to signal through the phosphatidylinositol 3′-kinase pathway leading to the activation of Akt, mTOR, and p70 S6K. Evidence presented here shows that E4orf1 may also induce the phosphorylation of Akt and p70 S6K in a manner that depends on Rac1 and its guanine nucleotide exchange factor Tiam1. Accordingly, agents that have been reported to disrupt the Tiam1-Rac1 interaction or to prevent phosphorylation of the ribosomal S6 kinase partially alleviated the E4orf1 restriction to late viral protein synthesis and enhanced tumor cell killing by the E1B-55K mutant virus. These results demonstrate that E4orf1 limits the oncolytic nature of a conditionally replicating adenovirus such as ONYX-015. The therapeutic value of similar oncolytic adenoviruses may be improved by abrogating E4orf1 function. PMID:19129452

E4orf1 limits the oncolytic potential of the E1B-55K deletion mutant adenovirus.

Science.gov (United States)

Thomas, Michael A; Broughton, Robin S; Goodrum, Felicia D; Ornelles, David A

2009-03-01

Clinical trials have shown oncolytic adenoviruses to be tumor selective with minimal toxicity toward normal tissue. The virus ONYX-015, in which the gene encoding the early region 1B 55-kDa (E1B-55K) protein is deleted, has been most effective when used in combination with either chemotherapy or radiation therapy. Therefore, improving the oncolytic nature of tumor-selective adenoviruses remains an important objective for improving this form of cancer therapy. Cells infected during the G(1) phase of the cell cycle with the E1B-55K deletion mutant virus exhibit a reduced rate of viral late protein synthesis, produce fewer viral progeny, and are less efficiently killed than cells infected during the S phase. Here we demonstrate that the G(1) restriction imposed on the E1B-55K deletion mutant virus is due to the viral oncogene encoded by open reading frame 1 of early region 4 (E4orf1). E4orf1 has been reported to signal through the phosphatidylinositol 3'-kinase pathway leading to the activation of Akt, mTOR, and p70 S6K. Evidence presented here shows that E4orf1 may also induce the phosphorylation of Akt and p70 S6K in a manner that depends on Rac1 and its guanine nucleotide exchange factor Tiam1. Accordingly, agents that have been reported to disrupt the Tiam1-Rac1 interaction or to prevent phosphorylation of the ribosomal S6 kinase partially alleviated the E4orf1 restriction to late viral protein synthesis and enhanced tumor cell killing by the E1B-55K mutant virus. These results demonstrate that E4orf1 limits the oncolytic nature of a conditionally replicating adenovirus such as ONYX-015. The therapeutic value of similar oncolytic adenoviruses may be improved by abrogating E4orf1 function.

X-1E on Lakebed

Science.gov (United States)

1955-01-01

The Bell Aircraft Corporation X-1E in 1955 on the Rogers Dry Lakebed near the NACA High-Speed Flight Station, Edwards, California. The X-1E was notable for being shorter, with a thinner wing than the X-1A, -B, and -D. Aerodynamic heating caused the ailerons, rudder, and elevators to remain unpainted throughout the X-1E's flight test program. When the ventral fins were added, they were left unpainted too. On August 31, 1956, the aircraft reached a top speed of 1,480 miles per hour (Mach 2.24). There were four versions of the Bell X-1 rocket-powered research aircraft that flew at the NACA High-Speed Flight Research Station, Edwards, California. The bullet-shaped X-1 aircraft were built by Bell Aircraft Corporation, Buffalo, N.Y. for the U.S. Army Air Forces (after 1947, U.S. Air Force) and the National Advisory Committee for Aeronautics (NACA). The X-1 Program was originally designated the XS-1 for EXperimental Supersonic. The X-1's mission was to investigate the transonic speed range (speeds from just below to just above the speed of sound) and, if possible, to break the 'sound barrier.' Three different X-1s were built and designated: X-1-1, X-1-2 (later modified to become the X-1E), and X-1-3. The basic X-1 aircraft were flown by a large number of different pilots from 1946 to 1951. The X-1 Program not only proved that humans could go beyond the speed of sound, it reinforced the understanding that technological barriers could be overcome. The X-1s pioneered many structural and aerodynamic advances including extremely thin, yet extremely strong wing sections; supersonic fuselage configurations; control system requirements; powerplant compatibility; and cockpit environments. The X-1 aircraft were the first transonic-capable aircraft to use an all-moving stabilizer. The flights of the X-1s opened up a new era in aviation. The first X-1 was air-launched unpowered from a Boeing B-29 Superfortress on January 25, 1946. Powered flights began in December 1946. On October 14

Genetic polymorphism analysis of cytochrome P4502E1 (CYP2E1) in a Chinese Tibetan population

Science.gov (United States)

Wang, Li; Ren, Guoxia; Li, Jingjie; Zhu, Linhao; Niu, Fanglin; Yan, Mengdan; Li, Jing; Yuan, Dongya; Jin, Tianbo

2017-01-01

Abstract Cytochrome P4502E1 (CYP2E1) gene genetic polymorphisms vary markedly in frequency among different ethnic and racial groups. We studied the genotype distributions and allele frequencies of 3 CYP2E1 polymorphisms: CYP2E1∗1A, CYP2E1∗7A, and CYP2E1∗7C by polymerase chain reaction technique in a sample of 100 healthy subjects representing Tibetan population. The frequencies of CYP2E1∗1A, ∗7A, and ∗7C alleles were 0.705, 0.125, and 0.170, respectively. Compared with other populations, we found that the allele frequencies of the variants −352A>G (rs2070672) and −333A>T (rs2070673) in this Tibetan population have significant differences compared with European-American, African-American, Japanese, Korean, and other different geographic areas in Chinese Han population. Furthermore, the results of protein prediction revealed that the variant 6397G>A (rs61710826) could influence the protein structure and function. These findings in this study would be valuable for pharmacogenetics for drug therapy and drug discovery. However, further studies in larger samples are warranted to confirm our results. PMID:29381998

E2F1 regulates cellular growth by mTORC1 signaling.

Directory of Open Access Journals (Sweden)

Sebastian Real

2011-01-01

Full Text Available During cell proliferation, growth must occur to maintain homeostatic cell size. Here we show that E2F1 is capable of inducing growth by regulating mTORC1 activity. The activation of cell growth and mTORC1 by E2F1 is dependent on both E2F1's ability to bind DNA and to regulate gene transcription, demonstrating that a gene induction expression program is required in this process. Unlike E2F1, E2F3 is unable to activate mTORC1, suggesting that growth activity could be restricted to individual E2F members. The effect of E2F1 on the activation of mTORC1 does not depend on Akt. Furthermore, over-expression of TSC2 does not interfere with the effect of E2F1, indicating that the E2F1-induced signal pathway can compensate for the inhibitory effect of TSC2 on Rheb. Immunolocalization studies demonstrate that E2F1 induces the translocation of mTORC1 to the late endosome vesicles, in a mechanism dependent of leucine. E2F1 and leucine, or insulin, together affect the activation of S6K stronger than alone suggesting that they are complementary in activating the signal pathway. From these studies, E2F1 emerges as a key protein that integrates cell division and growth, both of which are essential for cell proliferation.

The B(E2;4^+1->2^+1) / B(E2;2^+1->0^+1) Ratio in Even-Even Nuclei

Science.gov (United States)

Loelius, C.; Sharon, Y. Y.; Zamick, L.; G"Urdal, G.

2009-10-01

We considered 207 even-even nuclei throughout the chart of nuclides for which the NNDC Tables had data on the energies and lifetimes of the 2^+1 and 4^+1 states. Using these data we calculated for each nucleus the electric quadrupole transition strengths B(E2;4^+1->2^+1) and B(E2;2^+1->0^+1), as well as their ratio. The internal conversion coefficients were obtained by using the NNDC HSICC calculator. For each nucleus we plotted the B(E2) ratio against A, N, and Z. We found that for close to 90% of the nuclei considered the ratio had values between 0.5 and 2.5. Most of the outliers had magic numbers of protons or neutrons. Our ratio results were compared with the theoretical predictions for this ratio by different models--10/7 in the rotational model and 2 in the simplest vibrational model. In the rotational regions (for 150 220) the ratios were indeed close to 10/7. For the few nuclei thought to be vibrational the ratios were usually less than 2. Otherwise, we got a wide scatter of ratio values. Hence other models, including the NpNn scheme, must be considered in interpreting these results.

Denton E-beam Evaporator #1

Data.gov (United States)

Federal Laboratory Consortium — Description:CORAL Name: E-Beam Evap 1This is a dual e-beam/thermal evaporator for the deposition of metal and dielectric thin films. Materials available are: Ag, Al,...

Effects of different cellulases on the release of phenolic acids from rice straw during saccharification.

Science.gov (United States)

Xue, Yiyun; Wang, Xiahui; Chen, Xingxuan; Hu, Jiajun; Gao, Min-Tian; Li, Jixiang

2017-06-01

Effects of different cellulases on the release of phenolic acids from rice straw during saccharification were investigated in this study. All cellulases tested increased the contents of phenolic acids during saccharification. However, few free phenolic acids were detected, as they were present in conjugated form after saccharification when the cellulases from Trichoderma reesei, Trichoderma viride and Aspergillus niger were used. On the other hand, phenolic acids were present in free form when the Acremonium cellulolyticus cellulase was used. Assays of enzyme activity showed that, besides high cellulase activity, the A. cellulolyticus cellulase exhibited high feruloyl esterase (FAE) activity. A synergistic interaction between FAE and cellulase led to the increase in free phenolic acids, and thus an increase in antioxidative and antiradical activities of the phenolic acids. Moreover, a cost estimation demonstrated the feasibility of phenolic acids as value-added products to reduce the total production cost of ethanol. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adenovirus E1A/E1B Transformed Amniotic Fluid Cells Support Human Cytomegalovirus Replication

Directory of Open Access Journals (Sweden)

Natascha Krömmelbein

2016-02-01

Full Text Available The human cytomegalovirus (HCMV replicates to high titers in primary human fibroblast cell cultures. A variety of primary human cells and some tumor-derived cell lines do also support permissive HCMV replication, yet at low levels. Cell lines established by transfection of the transforming functions of adenoviruses have been notoriously resistant to HCMV replication and progeny production. Here, we provide first-time evidence that a permanent cell line immortalized by adenovirus type 5 E1A and E1B (CAP is supporting the full HCMV replication cycle and is releasing infectious progeny. The CAP cell line had previously been established from amniotic fluid cells which were likely derived from membranes of the developing fetus. These cells can be grown under serum-free conditions. HCMV efficiently penetrated CAP cells, expressed its immediate-early proteins and dispersed restrictive PML-bodies. Viral DNA replication was initiated and viral progeny became detectable by electron microscopy in CAP cells. Furthermore, infectious virus was released from CAP cells, yet to lower levels compared to fibroblasts. Subviral dense bodies were also secreted from CAP cells. The results show that E1A/E1B expression in transformed cells is not generally repressive to HCMV replication and that CAP cells may be a good substrate for dense body based vaccine production.

Infection with E1B-mutant adenovirus stabilizes p53 but blocks p53 acetylation and activity through E1A

DEFF Research Database (Denmark)

Savelyeva, I.; Dobbelstein, M.

2011-01-01

to the suppression of p21 transcription. Depending on the E1A conserved region 3, E1B-defective adenovirus impaired the ability of the transcription factor Sp1 to bind the p21 promoter. Moreover, the amino terminal region of E1A, binding the acetyl transferases p300 and CREB-binding protein, blocked p53 K382...... accumulation of p53, without obvious defects in p53 localization, phosphorylation, conformation and oligomerization. Nonetheless, p53 completely failed to induce its target genes in this scenario, for example, p21/CDKN1A, Mdm2 and PUMA. Two regions of the E1A gene products independently contributed...... acetylation in infected cells. Mutating either of these E1A regions, in addition to E1B, partially restored p21 mRNA levels. Our findings argue that adenovirus attenuates p53-mediated p21 induction, through at least two E1B-independent mechanisms. Other virus species and cancer cells may employ analogous...

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

E-Peptides Control Bioavailability of IGF-1

Science.gov (United States)

Piszczek, Agnieszka; Perlas, Emarald; Winn, Nadine; Nastasi, Tommaso; Rosenthal, Nadia

2012-01-01

Insulin-like growth factor 1 (IGF-1) is a potent cytoprotective growth factor that has attracted considerable attention as a promising therapeutic agent. Transgenic over-expression of IGF-1 propeptides facilitates protection and repair in a broad range of tissues, although transgenic mice over-expressing IGF-1 propeptides display little or no increase in IGF-1 serum levels, even with high levels of transgene expression. IGF-1 propeptides are encoded by multiple alternatively spliced transcripts including C-terminal extension (E) peptides, which are highly positively charged. In the present study, we use decellularized mouse tissue to show that the E-peptides facilitate in vitro binding of murine IGF-1 to the extracellular matrix (ECM) with varying affinities. This property is independent of IGF-1, since proteins consisting of the E-peptides fused to relaxin, a related member of the insulin superfamily, bound equally avidly to decellularized ECM. Thus, the E-peptides control IGF-1 bioavailability by preventing systemic circulation, offering a potentially powerful way to tether IGF-1 and other therapeutic proteins to the site of synthesis and/or administration. PMID:23251442

A theoretical and (e,2e) experimental investigation into the complete valence electronic structure of (1.1.1) propellane

Energy Technology Data Exchange (ETDEWEB)

Adcock, W.; Clark, C.I. [Flinders Univ. of South Australia, Bedford Park, SA (Australia); Brunger, M.J.; McCarthy, I.E. [Flinders Univ. of South Australia, Bedford Park, SA (Australia). School of Physical Sciences; Michalewicz, M.T. [CSIRO, Carlton, VIC (Australia). Division of Information Technology; Von Niessen, W. [Technische Univ., Braunschweig (Germany). Institute fur Physikalische and Theoretische Chemie; Weigold, E. [Australian National Univ., Canberra, ACT (Australia). Inst. of Advanced Studies; Winkler, D.A. [Commonwealth Scientific and Industrial Research Organisation (CSIRO), Clayton, VIC (Australia). Div. of Chemical Physics

1996-08-01

The first comprehensive electronic structural study of the complete valence shell of [1.1.1] propellane is reported. Binding energy spectra were measured in the energy regime 3.5-46.5 eV over a range of different target electron momentum so that individual orbital momentum profiles could also be determined. These binding energy spectra were collected using an energy dispersive multichannel electron momentum spectrometer at a total energy of 1000 eV, with a coincidence energy resolution of 1.38 eV and a momentum resolution of about 0.1 a.u. The experimental orbital electron momentum profiles are compared with those calculated in the plane wave impulse approximation (PWIA) using both a triple zeta plus polarisation level SCF wavefunction and a further 13 basis sets as calculated using Density Functional Theory (DFT). A critical comparison between the experimental an theoretical momentum distributions (MDs) allows to determine the optimum wavefunction for [1.1.1]propellane. In general, the level of agreement between the experimental and theoretical MDs for the optimum wavefunction for all of the respective valence orbitals was very good. The determination of this wavefunction then allowed to derive the chemically interesting molecular properties of [1.1.1]propellane. These include infrared spectra, bond lengths, bond orders, electron densities and many others. A summary of these results and a comparison of them with the previous results of other workers is presented with the level of agreement typically being good. In particular, the existence of the C1-C3 bridging bond with a bond order of 0.70 was confirmed. 59 refs., 4 tabs., 11 figs.

Search for narrow resonances in e+e- annihilation between 1.85 and 3.1 GeV with the KEDR detector

International Nuclear Information System (INIS)

Anashin, V.V.; Aulchenko, V.M.; Baldin, E.M.; Barladyan, A.K.; Barnyakov, A.Yu.; Barnyakov, M.Yu.; Baru, S.E.; Basok, I.Yu.; Beloborodova, O.L.; Blinov, A.E.; Blinov, V.E.; Bobrov, A.V.; Bobrovnikov, V.S.; Bogomyagkov, A.V.; Bondar, A.E.; Buzykaev, A.R.; Eidelman, S.I.; Grigoriev, D.N.; Glukhovchenko, Yu.M.; Gulevich, V.V.

2011-01-01

We report results of a search for narrow resonances in e + e - annihilation at center-of-mass energies between 1.85 and 3.1 GeV performed with the KEDR detector at the VEPP-4M e + e - collider. The upper limit on the leptonic width of a narrow resonance Γ ee R .Br(R→hadr)<120 eV has been obtained (at 90% C.L.).

Novel (1E,3E,5E-1,6-bis(Substituted phenylhexa-1,3,5-triene Analogs Inhibit Melanogenesis in B16F10 Cells and Zebrafish

Directory of Open Access Journals (Sweden)

Jisun Oh

2018-04-01

Full Text Available The present study aimed to evaluate the anti-melanogenic activity of 1,6-diphenyl-1,3,5-hexatriene and its derivatives in B16F10 murine melanoma cells and zebrafish embryos. Twenty five (1E,3E,5E-1,6-bis(substituted phenylhexa-1,3,5-triene analogs were synthesized and their non-cytotoxic effects were predictively analyzed using three-dimensional quantitative structure-activity relationship approach. Inhibitory activities of these synthetic compounds against melanin synthesis were determined by evaluating melanin content and melanogenic regulatory enzyme expression in B16F10 cells. The anti-melanogenic activity was verified by observing body pigmentation in zebrafishes treated with these compounds. Compound #2, #4, and #6 effectively decreased melanogenesis induced by α-melanocyte-stimulating hormone. In particular, compound #2 remarkably lowered the mRNA and protein expression levels of microphthalmia-associated transcription factor (MITF, tyrosinase (TYR, tyrosinase-related protein 1 (TYRP1, and TYRP2 in B16F10 cells and substantially reduced skin pigmentation in the developed larvae of zebrafish. These findings suggest that compound #2 may be used as an anti-melanogenic agent for cosmetic purpose.

Anomalous behaviors of E1/E2 deep level defects in 6H silicon carbide

International Nuclear Information System (INIS)

Chen, X.D.; Ling, C.C.; Gong, M.; Fung, S.; Beling, C.D.; Brauer, G.; Anwand, W.; Skorupa, W.

2005-01-01

Deep level defects E 1 /E 2 were observed in He-implanted, 0.3 and 1.7 MeV electron-irradiated n-type 6H-SiC. Similar to others' results, the behaviors of E 1 and E 2 (like the peak intensity ratio, the annealing behaviors or the introduction rates) often varied from sample to sample. This anomalous result is not expected of E 1 /E 2 being usually considered arising from the same defect located at the cubic and hexagonal sites respectively. The present study shows that this anomaly is due to another DLTS peak overlapping with the E 1 /E 2 . The activation energy and the capture cross section of this defect are E C -0.31 eV and σ∼8x10 -14 cm 2 , respectively

Adenovirus E4 open reading frame 4-induced dephosphorylation inhibits E1A activation of the E2 promoter and E2F-1-mediated transactivation independently of the retinoblastoma tumor suppressor protein

DEFF Research Database (Denmark)

Mannervik, M; Fan, S; Ström, A C

1999-01-01

of the viral E4 open reading frame 4 (E4-ORF4) protein. This effect does not to require the retinoblastoma protein that previously has been shown to regulate E2F activity. The inhibitory activity of E4-ORF4 appears to be specific because E4-ORF4 had little effect on, for example, E4-ORF6/7 transactivation......Previous studies have shown that the cell cycle-regulated E2F transcription factor is subjected to both positive and negative control by phosphorylation. Here we show that in transient transfection experiments, adenovirus E1A activation of the viral E2 promoter is abrogated by coexpression...... of the E2 promoter. We further show that the repressive effect of E4-ORF4 on E2 transcription works mainly through the E2F DNA-binding sites in the E2 promoter. In agreement with this, we find that E4-ORF4 inhibits E2F-1/DP-1-mediated transactivation. We also show that E4-ORF4 inhibits E2 mRNA expression...

Structural models of the membrane anchors of envelope glycoproteins E1 and E2 from pestiviruses

International Nuclear Information System (INIS)

Wang, Jimin; Li, Yue; Modis, Yorgo

2014-01-01

The membrane anchors of viral envelope proteins play essential roles in cell entry. Recent crystal structures of the ectodomain of envelope protein E2 from a pestivirus suggest that E2 belongs to a novel structural class of membrane fusion machinery. Based on geometric constraints from the E2 structures, we generated atomic models of the E1 and E2 membrane anchors using computational approaches. The E1 anchor contains two amphipathic perimembrane helices and one transmembrane helix; the E2 anchor contains a short helical hairpin stabilized in the membrane by an arginine residue, similar to flaviviruses. A pair of histidine residues in the E2 ectodomain may participate in pH sensing. The proposed atomic models point to Cys987 in E2 as the site of disulfide bond linkage with E1 to form E1–E2 heterodimers. The membrane anchor models provide structural constraints for the disulfide bonding pattern and overall backbone conformation of the E1 ectodomain. - Highlights: • Structures of pestivirus E2 proteins impose constraints on E1, E2 membrane anchors. • Atomic models of the E1 and E2 membrane anchors were generated in silico. • A “snorkeling” arginine completes the short helical hairpin in the E2 membrane anchor. • Roles in pH sensing and E1–E2 disulfide bond formation are proposed for E1 residues. • Implications for E1 ectodomain structure and disulfide bonding pattern are discussed

Structural models of the membrane anchors of envelope glycoproteins E1 and E2 from pestiviruses

Energy Technology Data Exchange (ETDEWEB)

Wang, Jimin, E-mail: jimin.wang@yale.edu; Li, Yue; Modis, Yorgo, E-mail: yorgo.modis@yale.edu

2014-04-15

The membrane anchors of viral envelope proteins play essential roles in cell entry. Recent crystal structures of the ectodomain of envelope protein E2 from a pestivirus suggest that E2 belongs to a novel structural class of membrane fusion machinery. Based on geometric constraints from the E2 structures, we generated atomic models of the E1 and E2 membrane anchors using computational approaches. The E1 anchor contains two amphipathic perimembrane helices and one transmembrane helix; the E2 anchor contains a short helical hairpin stabilized in the membrane by an arginine residue, similar to flaviviruses. A pair of histidine residues in the E2 ectodomain may participate in pH sensing. The proposed atomic models point to Cys987 in E2 as the site of disulfide bond linkage with E1 to form E1–E2 heterodimers. The membrane anchor models provide structural constraints for the disulfide bonding pattern and overall backbone conformation of the E1 ectodomain. - Highlights: • Structures of pestivirus E2 proteins impose constraints on E1, E2 membrane anchors. • Atomic models of the E1 and E2 membrane anchors were generated in silico. • A “snorkeling” arginine completes the short helical hairpin in the E2 membrane anchor. • Roles in pH sensing and E1–E2 disulfide bond formation are proposed for E1 residues. • Implications for E1 ectodomain structure and disulfide bonding pattern are discussed.

26 CFR 31.3231(e)-1 - Compensation.

Science.gov (United States)

2010-04-01

.... (a) Definition—(1) The term compensation has the same meaning as the term wages in section 3121(a... regarding the inclusion of fringe benefits in compensation, see § 31.3121(a)-1T. (6) Split-dollar life... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Compensation. 31.3231(e)-1 Section 31.3231(e)-1...

Metaloproteinases 1 e 7 e câncer colorretal Metalloproteinases 1 and 7 and colorectal cancer

Directory of Open Access Journals (Sweden)

Mário Jucá

2008-09-01

Full Text Available A metaloproteinase-1 (MMP-1 e a metaloproteinase-7 (MMP-7 são proteinases da matriz extracelular (MEC, zinco-dependentes, envolvidas no processo inicial da carcinogênese por permitirem a invasão tumoral na célula e promover o processo de metastatização. O polimorfismo dessas proteinases tem sido estudado recentemente com o objetivo de validar susa expressão e/ou atividade como marcador prognóstico. Evidências cumulativas revelam importante papel das MMP's 1 e 7 em diferentes fases da carcinogênese. A MMP-1 tem ação direta sobre a principal proteína da MEC, que é o colágeno do tecido intersticial conectivo. Sua expressão aumentada neste tecido pode indicar alto potencial de disseminação tumoral em diferentes tipos de câncer, incluindo o colorretal. A associação deste aumento da expressão também parece ser verdadeira para a MMP-7.The metalloproteinase-1 (MMP-1 and metalloproteinase-7 (MMP-7 are proteinases of the extracellular matrix (MEC, zinc-dependent, involved in the initial process of carcinogenesis, allowing the invasion by the tumor cell and promoting the process of metastasis. The polymorphism of these proteinases has been studied recently in order to validate its expression and / or activity as a marker prognosis. Evidence shows cumulative important role of MMPs 1 and 7 in different stages of carcinogenesis. The MMP-1 is direct action on the main protein of the MEC, which is the collagen of interstitial connective tissue. Its increased expression in this tissue may indicate high potential for spread in different tumor types of cancer, including colorectal. The association of this increase of expression also appears to be true for MMP-7.

Analysis list: E2f1 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available E2f1 Blood,Liver + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f1.1....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f1.5.tsv http://dbarchive.biosciencedbc.jp/kyus...hu-u/mm9/target/E2f1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/E2f1.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/E2f1.Liver.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Liver.gml ...

Functional processing and secretion of Chikungunya virus E1 and E2 glycoproteins in insect cells

Directory of Open Access Journals (Sweden)

Goldbach Rob W

2011-07-01

Full Text Available Abstract Background Chikungunya virus (CHIKV is a mosquito-borne, arthrogenic Alphavirus that causes large epidemics in Africa, South-East Asia and India. Recently, CHIKV has been transmitted to humans in Southern Europe by invading and now established Asian tiger mosquitoes. To study the processing of envelope proteins E1 and E2 and to develop a CHIKV subunit vaccine, C-terminally his-tagged E1 and E2 envelope glycoproteins were produced at high levels in insect cells with baculovirus vectors using their native signal peptides located in CHIKV 6K and E3, respectively. Results Expression in the presence of either tunicamycin or furin inhibitor showed that a substantial portion of recombinant intracellular E1 and precursor E3E2 was glycosylated, but that a smaller fraction of E3E2 was processed by furin into mature E3 and E2. Deletion of the C-terminal transmembrane domains of E1 and E2 enabled secretion of furin-cleaved, fully processed E1 and E2 subunits, which could then be efficiently purified from cell culture fluid via metal affinity chromatography. Confocal laser scanning microscopy on living baculovirus-infected Sf21 cells revealed that full-length E1 and E2 translocated to the plasma membrane, suggesting similar posttranslational processing of E1 and E2, as in a natural CHIKV infection. Baculovirus-directed expression of E1 displayed fusogenic activity as concluded from syncytia formation. CHIKV-E2 was able to induce neutralizing antibodies in rabbits. Conclusions Chikungunya virus glycoproteins could be functionally expressed at high levels in insect cells and are properly glycosylated and cleaved by furin. The ability of purified, secreted CHIKV-E2 to induce neutralizing antibodies in rabbits underscores the potential use of E2 in a subunit vaccine to prevent CHIKV infections.

Catarata e diabetes mellitus tipo 1

OpenAIRE

Pizzol,Melissa Manfroi Dal; Esteves,Jorge Freita; Sccoco,Caio Augusto; Roggia,Murilo Felix; Rosa,Carolina Maurente da; Lambert,José Humberto Franco; Canani,Luís Henrique

2008-01-01

OBJETIVO: Avaliar a prevalência de catarata e seus fatores de risco em uma população portadora de diabetes mellitus tipo 1 (DM1). MÉTODOS: Estudo de casos e controles de um banco de dados de 181 pacientes (362 olhos) com diagnóstico de diabetes mellitus tipo 1. Os pacientes foram classificados como casos quando apresentavam diagnóstico de catarata. As variáveis estudadas foram a presença ou não de retinopatia diabética, tratamento com panfotocoagulação, presença de hipertensão arterial sistêm...

Paleomagnetic study of areas B1, C1 and E2

International Nuclear Information System (INIS)

Barton, C.; Sopher, C.

1982-01-01

Sediments from all three areas retain a stable primary remanence with a small viscous overprint which can be removed by AF cleaning. This marginally reduces the scatter in NRM data and improves the constraints on some reversal boundaries. Excellent reversal stratigraphies exist in all cores, particularly within area E2, with the exception of core B1-43P. This core is normally magnetized throughout and has a larger viscous component than other cores. Sedimentation rates are slower during the Brunhes epoch in all cores except C1-32P and C1-33P. Cores C1-34P and E2-46P have almost constant sedimentation rates throughout. The abnormally low average sedimentation rate during the Brunhes in core C1-35P suggest a loss of up to 2m of sediment, either during coring or by in situ erosion. Overall sedimentation rates are highest in area B1, lowest in area E2, and show least variation between cores in area E2. There is no general correlation between lithology and the paleomagnetic record. Ash layers and horizons with abnormally low water contents sometimes coincide with spikes in the paleomagnetic records

Data of evolutionary structure change: 1E14L-1PCRM [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 1E14L-1PCRM 1E14 1PCR L M -ALLSFERKYRVPGGT-----LVGGNLFD----FWVGP-...entryChain> 1PCR M 1PCRM...dbChain>M 1PCRM YGLSFAAPLKE 1PCR M 1PCRM IADRG-----TAAER M 1PCRM TVVDN----WYVWG

Structural models of the membrane anchors of envelope glycoproteins E1 and E2 from pestiviruses

Science.gov (United States)

Wang, Jimin; Li, Yue; Modis, Yorgo

2014-01-01

The membrane anchors of viral envelope proteins play essential roles in cell entry. Recent crystal structures of the ectodomain of envelope protein E2 from a pestivirus suggest that E2 belongs to a novel structural class of membrane fusion machinery. Based on geometric constraints from the E2 structures, we generated atomic models of the E1 and E2 membrane anchors using computational approaches. The E1 anchor contains two amphipathic perimembrane helices and one transmembrane helix; the E2 anchor contains a short helical hairpin stabilized in the membrane by an arginine residue, similar to flaviviruses. A pair of histidine residues in the E2 ectodomain may participate in pH sensing. The proposed atomic models point to Cys987 in E2 as the site of disulfide bond linkage with E1 to form E1–E2 heterodimers. The membrane anchor models provide structural constraints for the disulfide bonding pattern and overall backbone conformation of the E1 ectodomain. PMID:24725935

e +e- modes and U(1) spontaneous chiral symmetry breaking

International Nuclear Information System (INIS)

Steininger, K.

1992-01-01

In this paper, motivated by evidence for a chiral phase transition in strong coupling lattice QED, the authors calculate the two-particle spectrum of the broken QED phase. This is done in the framework of a Nambu and Jona-Lasinio model with U(1) symmetry including chiral symmetry and symmetry breaking properties of QED. The second order chiral phase transition behavior in our model and in lattice QED are in excellent agreement. The authors then present a detailed analysis of the spectra of the e + e - modes in the broken phase. The authors examine whether these modes have any possible relationship to the narrow e + e - resonances found in soft heavy ion collisions at GSL. The authors' answer is negative

Synthesis and structural study on (1E,2E,1'E,2'E)-3,3'-bis[(4-bromophenyl)-3,3'-(4-methy-1,2-phenylene diimine)] acetaldehyde dioxime: A combined experimental and theoretical study

Science.gov (United States)

Topal, T.; Kart, H. H.; Tunay Taşlı, P.; Karapınar, E.

2015-06-01

Tetradentate (1E,2E,1'E,2'E)-3,3'-bis[(4-bromophenyl)-3,3'-(4-methy-1,2-phenylene diimine)] acetaldehyde dioxime which possess N4 donor sets derived from the condensation of isonitroso- p-bromoacetophenone and 3,4-diaminotoluene are synthesized and characterized. The characterization of tetradentate Schiff base ligand has been deduced from LC-MS, FTIR, 13C and 1H NMR spectra and elemental analysis. Furthermore, the molecular geometry, infrared and NMR spectra of the title molecule in the ground state have been calculated by using the quantum chemical computational methods such as density functional theory (DFT) and ab initio Hartree-Fock (HF) methods with the 6-31G(d) and 6-311G(d) basis sets. The computed bond lengths and bond angles by using the both methods show the good agreement with each other. Moreover, the vibrational frequencies have been calculated and the scaled values have been compared with the experimental FTIR spectroscopic data. Assignments of the vibrational modes are made on the basis of potential energy distribution (PED) calculated from by using VEDA program. The correlations between the observed and calculated frequencies are in good agreement with each other as well as the correlation of the NMR data.

CYP2E1 Metabolism of Styrene Involves Allostery

Science.gov (United States)

Hartman, Jessica H.; Boysen, Gunnar

2012-01-01

We are the first to report allosterism during styrene oxidation by recombinant CYP2E1 and human liver microsomes. At low styrene concentrations, oxidation is inefficient because of weak binding to CYP2E1 (Ks = 830 μM). A second styrene molecule then binds CYP2E1 with higher affinity (Kss = 110 μM) and significantly improves oxidation to achieve a kcat of 6.3 nmol · min−1 · nmol CYP2E1−1. The transition between these metabolic cycles coincides with reported styrene concentrations in blood from exposed workers; thus, this CYP2E1 mechanism may be relevant in vivo. Scaled modeling of the in vitro-positive allosteric mechanism for styrene metabolism to its in vivo clearance led to significant deviations from the traditional model based on Michaelis-Menten kinetics. Low styrene levels were notably much less toxic than generally assumed. We interrogated the allosteric mechanism using the CYP2E1-specific inhibitor and drug 4-methylpyrazole, which we have shown binds two CYP2E1 sites. From the current studies, styrene was a positive allosteric effector on 4-methylpyrazole binding, based on a 10-fold increase in 4-methylpyrazole binding affinity from Ki 0.51 to Ksi 0.043 μM. The inhibitor was a negative allosteric effector on styrene oxidation, because kcat decreased 6-fold to 0.98 nmol · min−1 · nmol CYP2E1−1. Consequently, mixtures of styrene and other molecules can induce allosteric effects on binding and metabolism by CYP2E1 and thus mitigate the efficiency of their metabolism and corresponding effects on human health. Taken together, our elucidation of mechanisms for these allosteric reactions provides a powerful tool for further investigating the complexities of CYP2E1 metabolism of drugs and pollutants. PMID:22807108

CDH1 regulates E2F1 degradation in response to differentiation signals in keratinocytes.

Science.gov (United States)

Singh, Randeep K; Dagnino, Lina

2017-01-17

The E2F1 transcription factor plays key roles in skin homeostasis. In the epidermis, E2F1 expression is essential for normal proliferation of undifferentiated keratinocytes, regeneration after injury and DNA repair following UV radiation-induced photodamage. Abnormal E2F1 expression promotes nonmelanoma skin carcinoma. In addition, E2F1 must be downregulated for proper keratinocyte differentiation, but the relevant mechanisms involved remain poorly understood. We show that differentiation signals induce a series of post-translational modifications in E2F1 that are jointly required for its downregulation. Analysis of the structural determinants that govern these processes revealed a central role for S403 and T433. In particular, substitution of these two amino acid residues with non-phosphorylatable alanine (E2F1 ST/A) interferes with E2F1 nuclear export, K11- and K48-linked polyubiquitylation and degradation in differentiated keratinocytes. In contrast, replacement of S403 and T433 with phosphomimetic aspartic acid to generate a pseudophosphorylated E2F1 mutant protein (E2F1 ST/D) generates a protein that is regulated in a manner indistinguishable from that of wild type E2F1. Cdh1 is an activating cofactor that interacts with the anaphase-promoting complex/cyclosome (APC/C) ubiquitin E3 ligase, promoting proteasomal degradation of various substrates. We found that Cdh1 associates with E2F1 in keratinocytes. Inhibition or RNAi-mediated silencing of Cdh1 prevents E2F1 degradation in response to differentiation signals. Our results reveal novel regulatory mechanisms that jointly modulate post-translational modifications and downregulation of E2F1, which are necessary for proper epidermal keratinocyte differentiation.

Identities of the deep level defects E1/E2 in 6H silicon carbide

International Nuclear Information System (INIS)

Ling, C.C.; Chen, X.D.; Beling, C.D.; Fung, S.; Lam, T.W.; Lam, C.H.; Gong, M.; Weng, H.M.; Hang, D.S.

2004-01-01

E 1 /E 2 (E C -0.36/0.44 eV) are deep level donors generally found in ion-implanted, electron and neutron irradiated n-type 6H-SiC materials. Their configurations are controversial and have been related to a negatively charged carbon vacancy, a divacancy or a V Si -complex. With positron lifetime technique, we have identified V Si and V C V Si in the Lely grown n-type 6H-SiC sample, with V Si annealed out at 650 C. Concentration of V C V Si persists at 1400 C annealing and significantly decreased after the 1600 C annealing. Considering the deep level transient spectroscopic (DLTS) results on the neutron irradiated n-type SiC epi sample that E 1 /E 2 completely disappeared after the 1400 C annealing, E 1 /E 2 is not the V C V Si defect. With positron annihilation techniques, A. A. Rempel et al (2002) have shown the energy dependence of vacancy generated by electron irradiation. With low irradiation energy of 0.3MeV, only V C was generated and at higher energy (0.5MeV), Si vacancy was detected. With focus to find the minimum energy for generating E 1 /E 2 , we have performed DLTS studies on n-type epi 6H-SiC materials irradiated by electrons with varying energies. Our results suggest that E 1 /E 2 have microstructure related to a carbon vacancy or a carbon interstitial. (orig.)

Separation of the longitudinal and transverse cross sections in the 1H(e,e(prime) K+)Λ and 1H(e,e(prime) K+)Σ0 reactions

International Nuclear Information System (INIS)

Mohring, R.M.; Abbott, David; Ahmidouch, Abdellah; Amatuni, Thomas; Pawel Ambrozewicz; Tatiana Angelescu; Christopher Armstrong; John Arrington; Ketevi Assamagan; Steven Avery; Kevin Bailey; Kevin Beard; S Beedoe; Elizabeth Beise; Herbert Breuer; Roger Carlini; Jinseok Cha; C. Chang; Nicholas Chant; Evaristo Cisbani; Glenn Collins; William Cummings; Samuel Danagoulian; Raffaele De Leo; Fraser Duncan; James Dunne; Dipangkar Dutta; T Eden; Rolf Ent; Laurent Eyraud; Lars Ewell; John Finn; H. Terry Fortune; Valera Frolov; Salvatore Frullani; Christophe Furget; Franco Garibaldi; David Gaskell; Donald Geesaman; Paul Gueye; Kenneth Gustafsson; Jens-Ole Hansen; Mark Harvey; Wendy Hinton; Ed Hungerford; Mauro Iodice; Ceasar Jackson; Cynthia Keppel; Wooyoung Kim; Kouichi Kino; Douglas Koltenuk; Serge Kox; Laird Kramer; Antonio Leone; Allison Lung; David Mack; Richard Madey; M Maeda; Stanislaw Majewski; Pete Markowitz; T Mart; C Martoff; David Meekins; A. Mihul; Joseph Mitchell; Hamlet Mkrtchyan; Sekazi Mtingwa; Maria-Ioana Niculescu; R. Perrino; David Potterveld; John Price; Brian Raue; Jean Sebastien Real; Joerg Reinhold; Philip Roos; Teijiro Saito; Geoff Savage; Reyad Sawafta; Ralph Segel; Stepan Stepanyan; Paul Stoler; Vardan Tadevosyan; Liguang Tang; Liliana Teodorescu; Tatsuo Terasawa; Hiroaki Tsubota; Guido Urciuoli; Jochen Volmer; William Vulcan; T. Welch; Robert Williams; Stephen Wood; Chen Yan; Benjamin Zeidman

2003-01-01

We report measurements of cross sections for the reaction 1 H(e,e(prime) K + )Y, for both the Λ and Σ 0 hyperon states, at an invariant mass of W = 1.84 GeV and four-momentum transfers 0.5 2 2 . Data were taken for three values of virtual photon polarization ε, allowing the decomposition of the cross sections into longitudinal and transverse components. The Λ data are a revised analysis of prior work, whereas the Σ 0 results have not been previously reported

Structure of a Glomulin-RBX1-CUL1 complex: inhibition of a RING E3 ligase through masking of its E2-binding surface

Science.gov (United States)

Duda, David M.; Olszewski, Jennifer L.; Tron, Adriana E.; Hammel, Michal; Lambert, Lester J.; Waddell, M. Brett; Mittag, Tanja; DeCaprio, James A.; Schulman, Brenda A.

2012-01-01

Summary The ~300 human Cullin-RING ligases (CRLs) are multisubunit E3s in which a RING protein, either RBX1 or RBX2, recruits an E2 to catalyze ubiquitination. RBX1-containing CRLs also can bind Glomulin (GLMN), which binds RBX1’s RING domain, regulates the RBX1-CUL1-containing SCFFBW7 complex, and is disrupted in the disease Glomuvenous Malformation. Here we report the crystal structure of a complex between GLMN, RBX1, and a fragment of CUL1. Structural and biochemical analyses reveal that GLMN adopts a HEAT-like repeat fold that tightly binds the E2-interacting surface of RBX1, inhibiting CRL-mediated chain formation by the E2 CDC34. The structure explains the basis for GLMN’s selectivity toward RBX1 over RBX2, and how disease-associated mutations disrupt GLMN-RBX1 interactions. Our study reveals a mechanism for RING E3 ligase regulation whereby an inhibitor blocks E2 access, and raises the possibility that other E3s are likewise controlled by cellular proteins that mask E2-binding surfaces to mediate inhibition. PMID:22748924

HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines

International Nuclear Information System (INIS)

Calmon, Marilia Freitas; Sichero, Laura; Boccardo, Enrique; Villa, Luisa Lina; Rahal, Paula

2016-01-01

Annexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes and in cells transduced with shRNA targeting E6AP. We observed that ANXA1 protein expression increased in HPV-16-positive tumor cells, in keratinocytes expressing HPV-16 E6wt (wild-type) or E6/E7 and C33 cells expressing HPV-16 E6wt. ANXA1 protein expression decreased in cells transfected with E6 Dicer-substrate RNAs (DsiRNA) and C33 cells cotransduced with HPV-16 E6wt and E6AP shRNA. Moreover, colony number and proliferation rate decreased in HPV16-positive cells transduced with ANXA1 shRNA. We observed that in cells infected with HPV16, the E6 binds to E6AP to degrade p53 and upregulate ANXA1. We suggest that ANXA1 may play a role in HPV-mediated carcinogenesis. - Highlights: • ANXA1 upregulation requires the presence of E6 and E6AP and is dependent on E6 integrity. • E6 binds to E6AP to degrade p53 and upregulate ANXA1 in cells infected with HPV16. • ANXA1 plays a role in cell proliferation in HPV-positive cervical cells.

HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines

Energy Technology Data Exchange (ETDEWEB)

Calmon, Marilia Freitas [Department of Biology, Institute of Bioscience, Language and Exact Science, São Paulo State University, São Jose do Rio Preto (Brazil); Sichero, Laura [Molecular Biology Laboratory, Centre for Translational Research in Oncology, Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo (Brazil); Boccardo, Enrique [Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo., São Paulo (Brazil); Villa, Luisa Lina [Department of Radiology and Oncology, Faculdade de Medicina, Universidade de São Paulo, São Paulo (Brazil); Rahal, Paula, E-mail: rahalp@yahoo.com.br [Department of Biology, Institute of Bioscience, Language and Exact Science, São Paulo State University, São Jose do Rio Preto (Brazil)

2016-09-15

Annexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes and in cells transduced with shRNA targeting E6AP. We observed that ANXA1 protein expression increased in HPV-16-positive tumor cells, in keratinocytes expressing HPV-16 E6wt (wild-type) or E6/E7 and C33 cells expressing HPV-16 E6wt. ANXA1 protein expression decreased in cells transfected with E6 Dicer-substrate RNAs (DsiRNA) and C33 cells cotransduced with HPV-16 E6wt and E6AP shRNA. Moreover, colony number and proliferation rate decreased in HPV16-positive cells transduced with ANXA1 shRNA. We observed that in cells infected with HPV16, the E6 binds to E6AP to degrade p53 and upregulate ANXA1. We suggest that ANXA1 may play a role in HPV-mediated carcinogenesis. - Highlights: • ANXA1 upregulation requires the presence of E6 and E6AP and is dependent on E6 integrity. • E6 binds to E6AP to degrade p53 and upregulate ANXA1 in cells infected with HPV16. • ANXA1 plays a role in cell proliferation in HPV-positive cervical cells.

The nuclear receptor NR2E1/TLX controls senescence

Science.gov (United States)

Krusche, Benjamin; Pemberton, Helen; Alonso, Marta M.; Chandler, Hollie; Brookes, Sharon; Parrinello, Simona; Peters, Gordon; Gil, Jesús

2014-01-01

The nuclear receptor NR2E1 (also known as TLX or tailless) controls the self-renewal of neural stem cells (NSCs) and has been implied as an oncogene which initiates brain tumours including glioblastomas. Despite NR2E1 regulating targets like p21CIP1 or PTEN we still lack a full explanation for its role in NSC self-renewal and tumorigenesis. We know that Polycomb repressive complexes (PRC) also control stem cell self-renewal and tumorigenesis, but so far, no formal connection has been established between NR2E1 and PRCs. In a screen for transcription factors regulating the expression of the Polycomb protein CBX7, we identified NR2E1 as one of its more prominent regulators. NR2E1 binds at the CBX7 promoter, inducing its expression. Notably CBX7 represses NR2E1 as part of a regulatory loop. Ectopic NR2E1 expression inhibits cellular senescence, extending cellular lifespan in fibroblasts via CBX7-mediated regulation of p16INK4a and direct repression of p21CIP1. In addition NR2E1 expression also counteracts oncogene-induced senescence (OIS). The importance of NR2E1 to restrain senescence is highlighted through the process of knocking down its expression, which causes premature senescence in human fibroblasts and epithelial cells. We also confirmed that NR2E1 regulates CBX7 and restrains senescence in NSCs. Finally, we observed that the expression of NR2E1 directly correlates with that of CBX7 in human glioblastoma multiforme. Overall we identified control of senescence and regulation of Polycomb action as two possible mechanisms that can join those so far invoked to explain the role of NR2E1 in control of NSC self-renewal and cancer. PMID:25328137

The nuclear receptor NR2E1/TLX controls senescence.

Science.gov (United States)

O'Loghlen, Ana; Martin, Nadine; Krusche, Benjamin; Pemberton, Helen; Alonso, Marta M; Chandler, Hollie; Brookes, Sharon; Parrinello, Simona; Peters, Gordon; Gil, Jesús

2015-07-30

The nuclear receptor NR2E1 (also known as TLX or tailless) controls the self-renewal of neural stem cells (NSCs) and has been implied as an oncogene which initiates brain tumors including glioblastomas. Despite NR2E1 regulating targets like p21(CIP1) or PTEN we still lack a full explanation for its role in NSC self-renewal and tumorigenesis. We know that polycomb repressive complexes also control stem cell self-renewal and tumorigenesis, but so far, no formal connection has been established between NR2E1 and PRCs. In a screen for transcription factors regulating the expression of the polycomb protein CBX7, we identified NR2E1 as one of its more prominent regulators. NR2E1 binds at the CBX7 promoter, inducing its expression. Notably CBX7 represses NR2E1 as part of a regulatory loop. Ectopic NR2E1 expression inhibits cellular senescence, extending cellular lifespan in fibroblasts via CBX7-mediated regulation of p16(INK4a) and direct repression of p21(CIP1). In addition NR2E1 expression also counteracts oncogene-induced senescence. The importance of NR2E1 to restrain senescence is highlighted through the process of knocking down its expression, which causes premature senescence in human fibroblasts and epithelial cells. We also confirmed that NR2E1 regulates CBX7 and restrains senescence in NSCs. Finally, we observed that the expression of NR2E1 directly correlates with that of CBX7 in human glioblastoma multiforme. Overall we identified control of senescence and regulation of polycomb action as two possible mechanisms that can join those so far invoked to explain the role of NR2E1 in control of NSC self-renewal and cancer.

Radiative rates for E1, E2, M1 and M2 transitions in Fe X

International Nuclear Information System (INIS)

Aggarwal, K.M.; Keenan, F.P.

2004-01-01

Energies of the 54 levels belonging to the (1s 2 2s 2 2p 6 ) 3s 2 3p 5 , 3s3p 6 , 3s 2 3p 4 3d and 3s3p 5 3d configurations of Fe X have been calculated using the GRASP code of Dyall and colleagues (1989). Additionally, radiative rates, oscillator strengths, and line strengths are calculated for all electric dipole (E1), magnetic dipole (M1), electric quadrupole (E2), and magnetic quadrupole (M2) transitions among these levels. Comparisons are made with results available in the literature, and the accuracy of the data is assessed. Our energy levels are estimated to be accurate to better than 3%, whereas results for other parameters are probably accurate to better than 20% . Additionally, the agreement between measured and calculated lifetimes is better than 10%. (authors)

Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform.

Science.gov (United States)

Gabitzsch, Elizabeth S; Balint-Junior, Joseph P; Xu, Younong; Balcaitis, Stephanie; Sanders-Beer, Brigitte; Karl, Julie; Weinhold, Kent J; Paessler, Slobodan; Jones, Frank R

2012-11-26

Anti-vector immunity mitigates immune responses induced by recombinant adenovirus vector vaccines, limiting their prime-boost capabilities. We have developed a novel gene delivery and expression platform (Ad5 [E1-, E2b-]) that induces immune responses despite pre-existing and/or developed concomitant Ad5 immunity. In the present study, we evaluated if this new Ad5 platform could overcome the adverse condition of pre-existing Ad5 immunity to induce effective immune responses in prime-boost immunization regimens against two different infectious diseases in the same animal. Ad5 immune rhesus macaques (RM) were immunized multiple times with the Ad5 [E1-, E2b-] platform expressing antigens from simian immunodeficiency virus (SIV). Immunized RM developed cell-mediated immunity against SIV antigens Gag, Pol, Nef and Env as well as antibody against Env. Vaccinated and vector control RMs were challenged intra-rectally with homologous SIVmac239. During a 7-week follow-up, there was perturbation of SIV load in some immunized RM. At 7 weeks post-challenge, eight immunized animals (53%) did not have detectable SIV, compared to two RM controls (13%) (Pnow hyper immune to Ad5, were then vaccinated with the same Ad5 [E1-, E2b-] platform expressing H1N1 influenza hemagglutinin (HA). Thirty days post Ad5 [E1-, E2b-]-HA vaccination, significant levels of influenza neutralizing antibody were induced in all animals that increased after an Ad5 [E1-, E2b-]-HA homologous boost. These data demonstrate the versatility of this new vector platform to immunize against two separate disease targets in the same animal despite the presence of immunity against the delivery platform, permitting homologous repeat immunizations with an Ad5 gene delivery platform. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Changes of biological behavioral of E. coli K1 after ppk1 gene deletion].

Science.gov (United States)

Peng, Liang; Pan, Jiayun; Luo, Su; Yang, Zhenghui; Huang, Mufang; Cao, Hong

2014-06-01

To study the changes in biological behaviors of meningitis E. coli K1 strain E44 after deletion of polyphosphate kinase 1 (ppk1) gene and explore the role of ppk1 in the pathogenesis of E. coli K1-induced meningitis. The wild-type strain E. coli K1 and ppk1 deletion mutant were exposed to heat at 56 degrees celsius; for 6 min, and their survival rates were determined. The adhesion and invasion of the bacteria to human brain microvascular endothelial cells (HBMECs) were observed using electron microscopy and quantitative tests. HBMECs were co-incubated with wild-type strain or ppk1 deletion mutant, and the cytoskeleton rearrangement was observed under laser scanning confocal microscope. The survival rate of the ppk1 deletion mutant was significantly lower than that of the wild-type strain after heat exposure. The ppk1 deletion mutant also showed lowered cell adhesion and invasion abilities and weakened ability to induce cytoskeleton rearrangement in HBMECs. ppk1 gene is important for E.coli K1 for heat resistance, cell adhesion and invasion, and for inducing cytoskeletal rearrangement in HBMECs.

1. What is E-Commerce?

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 5; Issue 10. Electronic Commerce - What is E-Commerce? V Rajaraman. Series Article Volume 5 Issue 10 October 2000 pp 13-23 ... Author Affiliations. V Rajaraman1. IBM Professor of Information Technology, JNCASR, Bangalore 560 064, India.

Production of β-xylosidase from Trichoderma asperellum KIF125 and its application in efficient hydrolysis of pretreated rice straw with fungal cellulase.

Science.gov (United States)

Inoue, Hiroyuki; Kitao, Chiaki; Yano, Shinichi; Sawayama, Shigeki

2016-11-01

On-site cellulase and hemicellulase production is a promising way to reduce enzyme cost in the commercialization of the lignocellulose-to-ethanol process. A hemicellulase-producing fungal strain suitable for on-site enzyme production was selected from cultures prepared using wet disc-milling rice straw (WDM-RS) and identified as Trichoderma asperellum KIF125. KIF125 hemicellulase showed uniquely high abundance of β-xylosidase in the xylanolytic enzyme system compared to other fungal hemicellulase preparations. Supplementation of Talaromyces cellulolyticus cellulase with KIF125 hemicellulase was more effective than that with the hemicellulases from other fungal sources in reducing the total enzyme loading for the improvement of xylose yield in the hydrolysis of ball-milling RS, due to its high β-xylosidase dominance. β-Xylosidase in KIF125 hemicellulase was purified and classified as a glycosyl hydrolase family 3 enzyme with relatively high specificity for xylobiose. The production of KIF125 β-xylosidase in the fermentor was estimated as 118 U/g-WDM-RS (2350 U/L culture) at 48 h. These results demonstrate that KIF125 is promising as a practical hemicellulase source to combine with on-site cellulase production using T. cellulolyticus.

Oncolytic Replication of E1b-Deleted Adenoviruses

Directory of Open Access Journals (Sweden)

Pei-Hsin Cheng

2015-11-01

Full Text Available Various viruses have been studied and developed for oncolytic virotherapies. In virotherapy, a relatively small amount of viruses used in an intratumoral injection preferentially replicate in and lyse cancer cells, leading to the release of amplified viral particles that spread the infection to the surrounding tumor cells and reduce the tumor mass. Adenoviruses (Ads are most commonly used for oncolytic virotherapy due to their infection efficacy, high titer production, safety, easy genetic modification, and well-studied replication characteristics. Ads with deletion of E1b55K preferentially replicate in and destroy cancer cells and have been used in multiple clinical trials. H101, one of the E1b55K-deleted Ads, has been used for the treatment of late-stage cancers as the first approved virotherapy agent. However, the mechanism of selective replication of E1b-deleted Ads in cancer cells is still not well characterized. This review will focus on three potential molecular mechanisms of oncolytic replication of E1b55K-deleted Ads. These mechanisms are based upon the functions of the viral E1B55K protein that are associated with p53 inhibition, late viralmRNAexport, and cell cycle disruption.

Dynamical (e,2e) studies of tetrahydropyran and 1,4-dioxane

Energy Technology Data Exchange (ETDEWEB)

Builth-Williams, J. D.; Chiari, L.; Jones, D. B., E-mail: darryl.jones@flinders.edu.au, E-mail: michael.brunger@flinders.edu.au [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Silva, G. B. da [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Universidade Federal de Mato Grosso, Barra do Garças, MT 78600-000 (Brazil); Chaluvadi, Hari; Madison, D. H. [Department of Physics, Missouri University of Science and Technology, Rolla, Missouri 65409 (United States); Brunger, M. J., E-mail: darryl.jones@flinders.edu.au, E-mail: michael.brunger@flinders.edu.au [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Institute of Mathematical Sciences, University of Malaya, 50603 Kuala Lumpur (Malaysia)

2014-06-07

We present experimental and theoretical results for the electron-impact ionization of the highest occupied molecular orbitals of tetrahydropyran and 1,4-dioxane. Using an (e,2e) technique in asymmetric coplanar kinematics, angular distributions of the slow ejected electron, with an energy of 20 eV, are measured when incident electrons at 250 eV ionize the target and scatter through an angle of either −10° or −15°. The data are compared with calculations performed at the molecular 3-body distorted wave level. Fair agreement between the theoretical model and the experimental measurements was observed. The similar structures for these targets provide key insights for assessing the limitations of the theoretical calculations. This study in turn facilitates an improved understanding of the dynamics in the ionization process.

The tumor suppressor gene hypermethylated in cancer 1 is transcriptionally regulated by E2F1

DEFF Research Database (Denmark)

Jenal, Mathias; Trinh, Emmanuelle; Britschgi, Christian

2009-01-01

to the HIC1 promoter was shown by chromatin immunoprecipitation assays in human TIG3 fibroblasts expressing tamoxifen-activated E2F1. In agreement, activation of E2F1 in TIG3-E2F1 cells markedly increased HIC1 expression. Interestingly, expression of E2F1 in the p53(-/-) hepatocellular carcinoma cell line...

Complete replication-competent adenovirus 11p vectors with E1 or E3 insertions show improved heat stability

Energy Technology Data Exchange (ETDEWEB)

Mei, Ya-Fang, E-mail: ya-fang.mei@umu.se [Department of Clinical Microbiology and Virology, Umeå University, SE-901 85 Umeå (Sweden); Wu, Haidong, E-mail: haidong.wu@umu.se [Department of Clinical Microbiology and Virology, Umeå University, SE-901 85 Umeå (Sweden); Hultenby, Kjell, E-mail: kjell.hultenby@ki.se [Division of Clinical Research Centre, Department of Laboratory Medicine, Karolinska Institute, SE-14186 Stockholm (Sweden); Silver, Jim, E-mail: jim.silver@umu.se [Department of Clinical Microbiology and Virology, Umeå University, SE-901 85 Umeå (Sweden)

2016-10-15

Conventional adenovirus vectors harboring E1 or E3 deletions followed by the insertion of an exogenous gene show considerably reduced virion stability. Here, we report strategies to generate complete replication-competent Ad11p(RCAd11p) vectors that overcome the above disadvantage. A GFP cassette was successfully introduced either upstream of E1A or in the E3A region. The resulting vectors showed high expression levels of the hexon and E1genes and also strongly induced the cytopathic effect in targeted cells. When harboring oversized genomes, the RCAd11pE1 and RCAd11pE3 vectors showed significantly improved heat stability in comparison to Ad11pwt;of the three, RCAd11pE3 was the most tolerant to heat treatment. Electron microscopy showed that RCAd11pE3, RCAd11pE1, Ad11pwt, and Ad11pE1 Delmanifested dominant, moderate, minimum, or no full virus particles after heat treatment at 47 °C for 5 h. Our results demonstrated that both genome size and the insertion site in the viral genome affect virion stability. -- Highlights: •Replicating adenovirus 11p GFP vectors at the E1 or E3 region were generated. •RCAd11pE3 and RCAd11pE1 vectors manifested significantly improved heat stability. •RCAd11pE3 and RCAd11pE1 showed more full viral particles than Ad11pwt after heating. •We demonstrated that both genome size and the insertion site affect virion stability.

Complete replication-competent adenovirus 11p vectors with E1 or E3 insertions show improved heat stability

International Nuclear Information System (INIS)

Mei, Ya-Fang; Wu, Haidong; Hultenby, Kjell; Silver, Jim

2016-01-01

Conventional adenovirus vectors harboring E1 or E3 deletions followed by the insertion of an exogenous gene show considerably reduced virion stability. Here, we report strategies to generate complete replication-competent Ad11p(RCAd11p) vectors that overcome the above disadvantage. A GFP cassette was successfully introduced either upstream of E1A or in the E3A region. The resulting vectors showed high expression levels of the hexon and E1genes and also strongly induced the cytopathic effect in targeted cells. When harboring oversized genomes, the RCAd11pE1 and RCAd11pE3 vectors showed significantly improved heat stability in comparison to Ad11pwt;of the three, RCAd11pE3 was the most tolerant to heat treatment. Electron microscopy showed that RCAd11pE3, RCAd11pE1, Ad11pwt, and Ad11pE1 Delmanifested dominant, moderate, minimum, or no full virus particles after heat treatment at 47 °C for 5 h. Our results demonstrated that both genome size and the insertion site in the viral genome affect virion stability. -- Highlights: •Replicating adenovirus 11p GFP vectors at the E1 or E3 region were generated. •RCAd11pE3 and RCAd11pE1 vectors manifested significantly improved heat stability. •RCAd11pE3 and RCAd11pE1 showed more full viral particles than Ad11pwt after heating. •We demonstrated that both genome size and the insertion site affect virion stability.

E-ELT M1 test facility

Science.gov (United States)

Dimmler, M.; Marrero, J.; Leveque, S.; Barriga, P.; Sedghi, B.; Mueller, M.

2012-09-01

During the advanced design phase of the European Extremely Large Telescope (E-ELT) several critical components have been prototyped. During the last year some of them have been tested in dedicated test stands. In particular, a representative section of the E-ELT primary mirror has been assembled with 2 active and 2 passive segments. This test stand is equipped with complete prototype segment subunits, i.e. including support mechanisms, glass segments, edge sensors, position actuators as well as additional metrology for monitoring. The purpose is to test various procedures such as calibration, alignment and handling and to study control strategies. In addition the achievable component and subsystem performances are evaluated, and interface issues are identified. In this paper an overview of the activities related to the E-ELT M1 Test Facility will be given. Experiences and test results are presented.

The Implementation of E1 Clock Recovery

Directory of Open Access Journals (Sweden)

Wang Ziyu

2016-01-01

Full Text Available Clock transform and recovery is of significant importance in microwave TDM service, and it is always extracted from the E1 line data stream in most cases. However, intrinsically uncertain delay and jitter caused by packet transmission of E1 data information, may lead to the indexes of the data recovery clock exceed the clock performance template. Through analysis of the E1 clock indexes and measuring methods, this paper proposes a new clock recovery method. The method employs two buffers, the first RAM is used as a buffer to deduct excess information, and the second FIFO is used as a buffer to recovery the clock and data. The first buffer has a feedback from the second one, and is able to actively respond to changes in the data link and requests from the second one. The test results validate the effectiveness of the method, and the corresponding scheme is also valuable for the other communication systems.

4E-BP1 regulates the differentiation of white adipose tissue.

Science.gov (United States)

Tsukiyama-Kohara, Kyoko; Katsume, Asao; Kimura, Kazuhiro; Saito, Masayuki; Kohara, Michinori

2013-07-01

4E Binding protein 1 (4E-BP1) suppresses translation initiation. The absence of 4E-BP1 drastically reduces the amount of adipose tissue in mice. To address the role of 4E-BP1 in adipocyte differentiation, we characterized 4E-BP1(-/-) mice in this study. The lack of 4E-BP1 decreased the amount of white adipose tissue and increased the amount of brown adipose tissue. In 4E-BP1(-/-) MEF cells, PPARγ coactivator 1 alpha (PGC-1α) expression increased and exogenous 4E-BP1 expression suppressed PGC-1α expression. The level of 4E-BP1 expression was higher in white adipocytes than in brown adipocytes and showed significantly greater up-regulation in white adipocytes than in brown adipocytes during preadipocyte differentiation into mature adipocytes. The amount of PGC-1α was consistently higher in HB cells (a brown preadipocyte cell line) than in HW cells (a white preadipocyte cell line) during differentiation. Moreover, the ectopic over-expression of 4E-BP1 suppressed PGC-1α expression in white adipocytes, but not in brown adipocytes. Thus, the results of our study indicate that 4E-BP1 may suppress brown adipocyte differentiation and PGC-1α expression in white adipose tissues. © 2013 The Authors Genes to Cells © 2013 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

Association of papillomavirus E6 proteins with either MAML1 or E6AP clusters E6 proteins by structure, function, and evolutionary relatedness.

Directory of Open Access Journals (Sweden)

Nicole Brimer

2017-12-01

Full Text Available Papillomavirus E6 proteins bind to LXXLL peptide motifs displayed on targeted cellular proteins. Alpha genus HPV E6 proteins associate with the cellular ubiquitin ligase E6AP (UBE3A, by binding to an LXXLL peptide (ELTLQELLGEE displayed by E6AP, thereby stimulating E6AP ubiquitin ligase activity. Beta, Gamma, and Delta genera E6 proteins bind a similar LXXLL peptide (WMSDLDDLLGS on the cellular transcriptional co-activator MAML1 and thereby repress Notch signaling. We expressed 45 different animal and human E6 proteins from diverse papillomavirus genera to ascertain the overall preference of E6 proteins for E6AP or MAML1. E6 proteins from all HPV genera except Alpha preferentially interacted with MAML1 over E6AP. Among animal papillomaviruses, E6 proteins from certain ungulate (SsPV1 from pigs and cetacean (porpoises and dolphins hosts functionally resembled Alpha genus HPV by binding and targeting the degradation of E6AP. Beta genus HPV E6 proteins functionally clustered with Delta, Pi, Tau, Gamma, Chi, Mu, Lambda, Iota, Dyokappa, Rho, and Dyolambda E6 proteins to bind and repress MAML1. None of the tested E6 proteins physically and functionally interacted with both MAML1 and E6AP, indicating an evolutionary split. Further, interaction of an E6 protein was insufficient to activate degradation of E6AP, indicating that E6 proteins that target E6AP co-evolved to separately acquire both binding and triggering of ubiquitin ligase activation. E6 proteins with similar biological function clustered together in phylogenetic trees and shared structural features. This suggests that the divergence of E6 proteins from either MAML1 or E6AP binding preference is a major event in papillomavirus evolution.

Simultaneous Cocirculation of Both European Varicella-Zoster Virus Genotypes (E1 and E2) in Mexico City▿

Science.gov (United States)

Rodríguez-Castillo, Araceli; Vaughan, Gilberto; Ramírez-González, José Ernesto; Escobar-Gutiérrez, Alejandro

2010-01-01

Full-length genome analysis of varicella-zoster virus (VZV) has shown that viral strains can be classified into seven different genotypes: European (E), Mosaic (M), and Japanese (J), and the E and M genotypes can be further subclassified into E1, E2, and M1 through 4, respectively. The distribution of the main VZV genotypes in Mexico was described earlier, demonstrating the predominance of E genotype, although other genotypes (M1 and M4) were also identified. However, no information regarding the circulation of either E genotype in the country is available. In the present study, we confirm the presence of both E1 and E2 genotypes in the country and explore the possibility of coinfection as the triggering factor for increased virulence among severe cases. A total of 61 different European VZV isolates collected in the Mexico City metropolitan area from 2005 to 2006 were typed by using a PCR method based on genotype-specific primer amplification. Fifty isolates belonged to the E1 genotype, and the eleven remaining samples were classified as E2 genotypes. No coinfection with both E genotypes was identified among these specimens. We provide here new information on the distribution of VZV genotypes circulating in Mexico City. PMID:20220168

DESIGN PACKAGE 1E SYSTEM SAFETY ANALYSIS

Energy Technology Data Exchange (ETDEWEB)

M. Salem

1995-06-23

The purpose of this analysis is to systematically identify and evaluate hazards related to the Yucca Mountain Project Exploratory Studies Facility (ESF) Design Package 1E, Surface Facilities, (for a list of design items included in the package 1E system safety analysis see section 3). This process is an integral part of the systems engineering process; whereby safety is considered during planning, design, testing, and construction. A largely qualitative approach was used since a radiological System Safety Analysis is not required. The risk assessment in this analysis characterizes the accident scenarios associated with the Design Package 1E structures/systems/components(S/S/Cs) in terms of relative risk and includes recommendations for mitigating all identified risks. The priority for recommending and implementing mitigation control features is: (1) Incorporate measures to reduce risks and hazards into the structure/system/component design, (2) add safety devices and capabilities to the designs that reduce risk, (3) provide devices that detect and warn personnel of hazardous conditions, and (4) develop procedures and conduct training to increase worker awareness of potential hazards, on methods to reduce exposure to hazards, and on the actions required to avoid accidents or correct hazardous conditions.

Neutronics and thermohydraulics of the reactor C.E.N.E. Pt. 1

International Nuclear Information System (INIS)

Caro, R.; Ahnert, C.; Esteban Naudin, A.; Martinez Fanegas, R.; Minguez, E.; Rovira, A.

1976-01-01

The analysis of neutronics (both statics and kinetics), of the 10 Mwt swimming pool reactor C.E.N.E. is included. A short description of the theoretical model used, along with the theoretical versus experimental cheking, carried out, whenever possible, with the reactors JEN-1 and JEN-2 of Junta de Energia Nuclear, is given in each of these chapters. (author) [es

Sites of disruption within E1 and E2 genes of HPV16 and association with cervical dysplasia.

Science.gov (United States)

Tsakogiannis, D; Gortsilas, P; Kyriakopoulou, Z; Ruether, I G A; Dimitriou, T G; Orfanoudakis, G; Markoulatos, P

2015-11-01

Integration of HPV16 DNA into the host chromosome usually disrupts the E1 and/or E2 genes. The present study investigated the disruption of E1, E2 genes in a total of eighty four HPV16-positive precancerous and cervical cancer specimens derived from Greek women (seventeen paraffin-embedded cervical biopsies and sixty seven Thin Prep samples). Complete E2 and E1 genes were amplified using three and nine overlapping primer sets respectively, in order to define the sites of disruption. Extensive mapping analysis revealed that disruption/deletion events within E2 gene occurred in high grade and cervical cancer samples (x(2) test, P disruption was documented among low grade cervical intraepithelial neoplasias. In addition, disruptions within the E1 gene occur both in high and low grade cervical intraepithelial neoplasia. This leads to the assumption that in low grade cervical intraepithelial neoplasias only E1 gene disruption was involved (Fisher's exact test, P disruption of E1 gene was located between nucleotides 1059 and 1323, while the most prevalent deleted region of the E2 gene was located between nucleotides 3172 and 3649 (E2 hinge region). Therefore, it is proposed that each population has its own profile of frequencies and sites of disruptions and extensive mapping analysis of E1 and E2 genes is mandatory in order to determine suitable markers for HPV16 DNA integration analysis in distinct populations. © 2015 Wiley Periodicals, Inc.

Simultaneous Cocirculation of Both European Varicella-Zoster Virus Genotypes (E1 and E2) in Mexico City▿

OpenAIRE

Rodríguez-Castillo, Araceli; Vaughan, Gilberto; Ramírez-González, José Ernesto; Escobar-Gutiérrez, Alejandro

2010-01-01

Full-length genome analysis of varicella-zoster virus (VZV) has shown that viral strains can be classified into seven different genotypes: European (E), Mosaic (M), and Japanese (J), and the E and M genotypes can be further subclassified into E1, E2, and M1 through 4, respectively. The distribution of the main VZV genotypes in Mexico was described earlier, demonstrating the predominance of E genotype, although other genotypes (M1 and M4) were also identified. However, no information regarding...

Diabetes and exocrine pancreatic insufficiency in E2F1/E2F2 double-mutant mice.

Science.gov (United States)

Iglesias, Ainhoa; Murga, Matilde; Laresgoiti, Usua; Skoudy, Anouchka; Bernales, Irantzu; Fullaondo, Asier; Moreno, Bernardino; Lloreta, José; Field, Seth J; Real, Francisco X; Zubiaga, Ana M

2004-05-01

E2F transcription factors are thought to be key regulators of cell growth control. Here we use mutant mouse strains to investigate the function of E2F1 and E2F2 in vivo. E2F1/E2F2 compound-mutant mice develop nonautoimmune insulin-deficient diabetes and exocrine pancreatic dysfunction characterized by endocrine and exocrine cell dysplasia, a reduction in the number and size of acini and islets, and their replacement by ductal structures and adipose tissue. Mutant pancreatic cells exhibit increased rates of DNA replication but also of apoptosis, resulting in severe pancreatic atrophy. The expression of genes involved in DNA replication and cell cycle control was upregulated in the E2F1/E2F2 compound-mutant pancreas, suggesting that their expression is repressed by E2F1/E2F2 activities and that the inappropriate cell cycle found in the mutant pancreas is likely the result of the deregulated expression of these genes. Interestingly, the expression of ductal cell and adipocyte differentiation marker genes was also upregulated, whereas expression of pancreatic cell marker genes were downregulated. These results suggest that E2F1/E2F2 activity negatively controls growth of mature pancreatic cells and is necessary for the maintenance of differentiated pancreatic phenotypes in the adult.

Heterodimerization of the transcription factors E2F-1 and DP-1 is required for binding to the adenovirus E4 (ORF6/7) protein

DEFF Research Database (Denmark)

Helin, K; Harlow, E

1994-01-01

Adenovirus infection leads to E1A-dependent activation of the transcription factor E2F. E2F has recently been identified in complexes with cellular proteins such as the retinoblastoma protein (pRB) and the two pRB family members p107 and p130. E1A dissociates E2F from these cellular proteins...

Hepatitis C Virus E1 and E2 Proteins Used as Separate Immunogens Induce Neutralizing Antibodies with Additive Properties.

Directory of Open Access Journals (Sweden)

Elodie Beaumont

Full Text Available Various strategies involving the use of hepatitis C virus (HCV E1 and E2 envelope glycoproteins as immunogens have been developed for prophylactic vaccination against HCV. However, the ideal mode of processing and presenting these immunogens for effective vaccination has yet to be determined. We used our recently described vaccine candidate based on full-length HCV E1 or E2 glycoproteins fused to the heterologous hepatitis B virus S envelope protein to compare the use of the E1 and E2 proteins as separate immunogens with their use as the E1E2 heterodimer, in terms of immunogenetic potential and the capacity to induce neutralizing antibodies. The specific anti-E1 and anti-E2 antibody responses induced in animals immunized with vaccine particles harboring the heterodimer were profoundly impaired with respect to those in animals immunized with particles harboring E1 and E2 separately. Moreover, the anti-E1 and anti-E2 antibodies had additive neutralizing properties that increase the cross-neutralization of heterologous strains of various HCV genotypes, highlighting the importance of including both E1 and E2 in the vaccine for an effective vaccination strategy. Our study has important implications for the optimization of HCV vaccination strategies based on HCV envelope proteins, regardless of the platform used to present these proteins to the immune system.

Cyclin E/Cdk2, P/CAF, and E1A regulate the transactivation of the c-myc promoter by FOXM1

International Nuclear Information System (INIS)

Wierstra, Inken; Alves, Juergen

2008-01-01

FOXM1c transactivates the c-myc promoter by binding directly to its TATA-boxes. The present study demonstrates that the transactivation of the c-myc promoter by FOXM1c is enhanced by the key proliferation signal cyclin E/Cdk2, but repressed by P/CAF and the adenoviral oncoprotein E1A. Furthermore, FOXM1c interacts with the coactivator and histone acetyltransferase P/CAF. This study shows that, on the c-myc-P1 TATA-box, FOXM1c does not function simply as normal transcription factor just binding to an unusual site. Moreover, the inhibitory N-terminus of FOXM1c does not inhibit its transrepression domain or its EDA. Others reported that a cyclin/Cdk-binding LXL-motif of the splice variant FoxM1b is required for its interaction with Cdk2, Cdk1, and p27, its phosphorylation by Cdk1 and its activation by Cdc25B. In contrast, we now demonstrate that this LXL-motif is not required for the activation of FOXM1c by cyclin D1/Cdk4, cyclin E/Cdk and cyclin A/Cdk2 or for the repression of FOXM1c by p27

A recombinant E1-deleted porcine adenovirus-3 as an expression vector

International Nuclear Information System (INIS)

Zakhartchouk, Alexander; Zhou Yan; Tikoo, Suresh Kumar

2003-01-01

Replication-defective E1-deleted porcine adenoviruses (PAVs) are attractive vectors for vaccination. As a prerequisite for generating PAV-3 vectors containing complete deletion of E1, we transfected VIDO R1 cells (fetal porcine retina cells transformed with E1 region of human adenovirus 5) with a construct containing PAV-3 E1B large coding sequences under the control of HCMV promoter. A cell line named VR1BL could be isolated that expressed E1B large of PAV-3 and also complemented PAV214 (E1A+E1B small deleted). The VR1BL cells could be efficiently transfected with DNA and allowed the rescue and propagation of recombinant PAV507 containing a triple stop codon inserted in the E1B large coding sequence. In addition, recombinant PAV227 containing complete deletion of E1 (E1A+E1B small + E1B large ) could be successfully rescued using VR1BL cell line. Recombinant PAV227 replicated as efficiently as wild-type in VR1BL cells but not in VIDO R1 cells, suggesting that E1B large was essential for replication of PAV-3. Next, we constructed recombinant PAV219 by inserting green fluorescent (GFP) protein gene flanked by a promoter and a poly(A) in the E1 region of the PAV227 genome. We demonstrated that PAV219 was able to transduce and direct expression of GFP in some human cell lines

Adenovirus type 5 E1A and E6 proteins of low-risk cutaneous beta-human papillomaviruses suppress cell transformation through interaction with FOXK1/K2 transcription factors.

Science.gov (United States)

Komorek, Jessica; Kuppuswamy, Mohan; Subramanian, T; Vijayalingam, S; Lomonosova, Elena; Zhao, Ling-Jun; Mymryk, Joe S; Schmitt, Kimberly; Chinnadurai, G

2010-03-01

The adenovirus (Adv) oncoprotein E1A stimulates cell proliferation and inhibits differentiation. These activities are primarily linked to the N-terminal region (exon 1) of E1A, which interacts with multiple cellular protein complexes. The C terminus (exon 2) of E1A antagonizes these processes, mediated in part through interaction with C-terminal binding proteins 1 and 2 (CtBP1/2). To identify additional cellular E1A targets that are involved in the modulation of E1A C-terminus-mediated activities, we undertook tandem affinity purification of E1A-associated proteins. Through mass spectrometric analysis, we identified several known E1A-interacting proteins as well as novel E1A targets, such as the forkhead transcription factors, FOXK1/K2. We identified a Ser/Thr-containing sequence motif in E1A that mediated interaction with FOXK1/K2. We demonstrated that the E6 proteins of two beta-human papillomaviruses (HPV14 and HPV21) associated with epidermodysplasia verruciformis also interacted with FOXK1/K2 through a motif similar to that of E1A. The E1A mutants deficient in interaction with FOXK1/K2 induced enhanced cell proliferation and oncogenic transformation. The hypertransforming activity of the mutant E1A was suppressed by HPV21 E6. An E1A-E6 chimeric protein containing the Ser/Thr domain of the E6 protein in E1A interacted efficiently with FOXK1/K2 and inhibited cell transformation. Our results suggest that targeting FOXK1/K2 may be a common mechanism for certain beta-HPVs and Adv5. E1A exon 2 mutants deficient in interaction with the dual-specificity kinases DYRK1A/1B and their cofactor HAN11 also induced increased cell proliferation and transformation. Our results suggest that the E1A C-terminal region may suppress cell proliferation and oncogenic transformation through interaction with three different cellular protein complexes: FOXK1/K2, DYRK(1A/1B)/HAN11, and CtBP1/2.

Melanocortin 1 Receptor Deficiency Promotes Atherosclerosis in Apolipoprotein E-/- Mice.

Science.gov (United States)

Rinne, Petteri; Kadiri, James J; Velasco-Delgado, Mauricio; Nuutinen, Salla; Viitala, Miro; Hollmén, Maija; Rami, Martina; Savontaus, Eriika; Steffens, Sabine

2018-02-01

The MC1-R (melanocortin 1 receptor) is expressed by monocytes and macrophages where it mediates anti-inflammatory actions. MC1-R also protects against macrophage foam cell formation primarily by promoting cholesterol efflux through the ABCA1 (ATP-binding cassette transporter subfamily A member 1) and ABCG1 (ATP-binding cassette transporter subfamily G member 1). In this study, we aimed to investigate whether global deficiency in MC1-R signaling affects the development of atherosclerosis. Apoe -/- (apolipoprotein E deficient) mice were crossed with recessive yellow (Mc1r e/e ) mice carrying dysfunctional MC1-R and fed a high-fat diet to induce atherosclerosis. Apoe -/- Mc1r e/e mice developed significantly larger atherosclerotic lesions in the aortic sinus and in the whole aorta compared with Apoe -/- controls. In terms of plaque composition, MC1-R deficiency was associated with less collagen and smooth muscle cells and increased necrotic core, indicative of more vulnerable lesions. These changes were accompanied by reduced Abca1 and Abcg1 expression in the aorta. Furthermore, Apoe -/- Mc1r e/e mice showed a defect in bile acid metabolism that aggravated high-fat diet-induced hypercholesterolemia and hepatic lipid accumulation. Flow cytometric analysis of leukocyte profile revealed that dysfunctional MC1-R enhanced arterial accumulation of classical Ly6C high monocytes and macrophages, effects that were evident in mice fed a normal chow diet but not under high-fat diet conditions. In support of enhanced arterial recruitment of Ly6C high monocytes, these cells had increased expression of L-selectin and P-selectin glycoprotein ligand 1. The present study highlights the importance of MC1-R in the development of atherosclerosis. Deficiency in MC1-R signaling exacerbates atherosclerosis by disturbing cholesterol handling and by increasing arterial monocyte accumulation. © 2017 The Authors.

eCD4-Ig variants that more potently neutralize HIV-1.

Science.gov (United States)

Fetzer, Ina; Gardner, Matthew R; Davis-Gardner, Meredith E; Prasad, Neha R; Alfant, Barnett; Weber, Jesse A; Farzan, Michael

2018-03-28

The HIV-1 entry inhibitor eCD4-Ig is a fusion of CD4-Ig and a coreceptor-mimetic peptide. eCD4-Ig is markedly more potent than CD4-Ig, with neutralization efficiencies approaching those of HIV-1 broadly neutralizing antibodies (bNAbs). However, unlike bNAbs, eCD4-Ig neutralizes all HIV-1, HIV-2 and SIV isolates that it has been tested against, suggesting that it may be useful in clinical settings where antibody escape is a concern. Here we characterize three new eCD4-Ig variants, each with different architectures and each utilizing D1.22, a stabilized form of CD4 domain 1. These variants were 10- to 20-fold more potent than our original eCD4-Ig variant, with a construct bearing four D1.22 domains (eD1.22-HL-Ig) exhibiting the greatest potency. However, this variant mediated less efficient antibody-dependent cell-mediated cytotoxicity (ADCC) activity than eCD4-Ig itself or several other eCD4-Ig variants, including the smallest variant (eD1.22-Ig). A variant with the same architecture as original eCD4-Ig (eD1.22-D2-Ig) showed modestly higher thermal stability and best prevented promotion of infection of CCR5-positive, CD4-negative cells. All three variants, and eCD4-Ig itself, mediated more efficient shedding of the HIV-1 envelope glycoprotein gp120 than did CD4-Ig. Finally, we show that only three D1.22 mutations contributed to the potency of eD1.22-D2-Ig, and that introduction of these changes into eCD4-Ig resulted in a variant 9-fold more potent than eCD4-Ig and 2-fold more potent than eD1.22-D2-Ig. These studies will assist in developing eCD4-Ig variants with properties optimized for prophylaxis, therapy, and cure applications. IMPORTANCE HIV-1 bNAbs have properties different from antiretroviral compounds. Specifically, antibodies can enlist immune effector cells to eliminate infected cells, whereas antiretroviral compounds simply interfere with various steps in the viral lifecycle. Unfortunately, HIV-1 is adept at evading antibody recognition, limiting the

Dosage-dependent copy number gains in E2f1 and E2f3 drive hepatocellular carcinoma.

Science.gov (United States)

Kent, Lindsey N; Bae, Sooin; Tsai, Shih-Yin; Tang, Xing; Srivastava, Arunima; Koivisto, Christopher; Martin, Chelsea K; Ridolfi, Elisa; Miller, Grace C; Zorko, Sarah M; Plevris, Emilia; Hadjiyannis, Yannis; Perez, Miguel; Nolan, Eric; Kladney, Raleigh; Westendorp, Bart; de Bruin, Alain; Fernandez, Soledad; Rosol, Thomas J; Pohar, Kamal S; Pipas, James M; Leone, Gustavo

2017-03-01

Disruption of the retinoblastoma (RB) tumor suppressor pathway, either through genetic mutation of upstream regulatory components or mutation of RB1 itself, is believed to be a required event in cancer. However, genetic alterations in the RB-regulated E2F family of transcription factors are infrequent, casting doubt on a direct role for E2Fs in driving cancer. In this work, a mutation analysis of human cancer revealed subtle but impactful copy number gains in E2F1 and E2F3 in hepatocellular carcinoma (HCC). Using a series of loss- and gain-of-function alleles to dial E2F transcriptional output, we have shown that copy number gains in E2f1 or E2f3b resulted in dosage-dependent spontaneous HCC in mice without the involvement of additional organs. Conversely, germ-line loss of E2f1 or E2f3b, but not E2f3a, protected mice against HCC. Combinatorial mapping of chromatin occupancy and transcriptome profiling identified an E2F1- and E2F3B-driven transcriptional program that was associated with development and progression of HCC. These findings demonstrate a direct and cell-autonomous role for E2F activators in human cancer.

The BPS spectrum of the 4d {N}=2 SCFT's H 1, H 2, D 4, E 6, E 7, E 8

Science.gov (United States)

Cecotti, Sergio; Del Zotto, Michele

2013-06-01

Extending results of 1112.3984, we show that all rank 1 {N}=2 SCFT's in the sequence H 1, H 2, D 4 E 6, E 7, E 8 have canonical finite BPS chambers containing precisely 2 h(F) = 12(∆ - 1) hypermultiplets. The BPS spectrum of the canonical BPS chambers saturates the conformal central charge c, and satisfies some intriguing numerology.

The cognition-enhancing activity of E1R, a novel positive allosteric modulator of sigma-1 receptors

Science.gov (United States)

Zvejniece, L; Vavers, E; Svalbe, B; Vilskersts, R; Domracheva, I; Vorona, M; Veinberg, G; Misane, I; Stonans, I; Kalvinsh, I; Dambrova, M

2014-01-01

Background and Purpose Here, we describe the in vitro and in vivo effects of (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide (E1R), a novel positive allosteric modulator of sigma-1 receptors. Experimental Approach E1R was tested for sigma receptor binding activity in a [3H](+)-pentazocine assay, in bradykinin (BK)-induced intracellular Ca2+ concentration ([Ca2+]i) assays and in an electrically stimulated rat vas deferens model. E1R's effects on cognitive function were tested using passive avoidance (PA) and Y-maze tests in mice. A selective sigma-1 receptor antagonist (NE-100), was used to study the involvement of the sigma-1 receptor in the effects of E1R. The open-field test was used to detect the effects of E1R on locomotion. Key Results Pretreatment with E1R enhanced the selective sigma-1 receptor agonist PRE-084's stimulating effect during a model study employing electrically stimulated rat vasa deferentia and an assay measuring the BK-induced [Ca2+]i increase. Pretreatment with E1R facilitated PA retention in a dose-related manner. Furthermore, E1R alleviated the scopolamine-induced cognitive impairment during the PA and Y-maze tests in mice. The in vivo and in vitro effects of E1R were blocked by treatment with the selective sigma-1 receptor antagonist NE-100. E1R did not affect locomotor activity. Conclusion and Implications E1R is a novel 4,5-disubstituted derivative of piracetam that enhances cognition and demonstrates efficacy against scopolamine-induced cholinergic dysfunction in mice. These effects are attributed to its positive modulatory action on the sigma-1 receptor and this activity may be relevant when developing new drugs for treating cognitive symptoms related to neurodegenerative diseases. PMID:24490863

Procedure for qualify class 1E equipment for nuclear power generating stations; Kvalifikacija elektroopreme za stjecanje klase 1E u nuklearnim elektranama

Energy Technology Data Exchange (ETDEWEB)

Smiljanic, D [' Rade Koncar' Institut, Zagreb (Yugoslavia)

1983-07-01

This paper describes the basic requirements for qualifying Class 1E equipment and systems that are to be used in nuclear power generating stations. The requirements presented include the principles, procedures and methods of qualification. The qualification requirements will confirm the adequacy of the equipment design under normal, abnormal, design basis event, post design basis event and containment test conditions for the performance of Class 1 E functions. The presented methods of qualification are in accordance with IEEE Standards and other standards (IEC, JUS, DIN, etc,), and have the primary role to provide guidance for demonstrating the qualification of Class 1E equipment produced by 'Rade Koncar'.(author)

An inhibitory switch derepressed by pbx, hox, and Meis/Prep1 partners regulates DNA-binding by pbx1 and E2a-pbx1 and is dispensable for myeloid immortalization by E2a-pbx1.

Science.gov (United States)

Calvo, K R; Knoepfler, P; McGrath, S; Kamps, M P

1999-12-23

The Pbx/Exd family of homeodomain (HD) proteins contribute to the transcriptional and developmental roles of other Hox and Meis/Prep1/Hth HD proteins through heterodimer formation. E2a-Pbx1 is an oncogenic derrivative of Pbx1 produced by the t(1;19) translocation in pediatric pre-B cell acute lymphoblastic leukemia. E2a-Pbx1 heterodimerizes with Hox but not with Meis/Prep1 proteins, produces acute myeloid leukemia in mice, and blocks differentiation of cultured murine myeloid progenitors. Here, we characterize negative and positive regulatory sequences that flank the Pbx1 HD and determine their importance for myeloid immortalization by E2a-Pbx1. A 25 residue predicted alpha helix preceding the Pbx1 HD bound the HD and prevented both its binding to DNA and its ability to heterodimerize with Hox proteins. Addition of 39 residues N-terminal to this inhibitory helix exposed a Pbx dimerization interface that orchestrated cooperative DNA-binding of E2a-Pbx1 and all Pbx proteins as homodimers and heterdimers. Sequences inhibiting DNA-binding and mediating Pbx dimerization coincided with those reported to have nuclear export function. An additional 103 residues N-terminal to the Pbx dimerization interface restored heterodimerization with Hox and Meis1/Prep1 proteins. This negative switch domain - comprised of the inhibitory helix and N-terminal regions required for its partner-mediated derepression - was dispensable for myeloid immortalization by E2a-Pbx1. While stabilizing the heterodimer, the 310 helix C-terminal to the Pbx1 HD was also dispensable for the ability of E2a-Pbx1 to heterodimerize with Hox proteins and immortalize myeloblasts. Retention of myeloid immortalization by E2a-Pbx1 proteins lacking all Pbx1 sequences N- or C-terminal to the HD indicates that Hox proteins, or a yet undefined factor that binds the Pbx1 HD and derepresses DNA-binding by the HD, cooperate with E2a-Pbx1 in myeloid immortalization.

Acetaldehyde and parkinsonism: role of CYP450 2E1

Directory of Open Access Journals (Sweden)

Francesca eVaglini

2013-06-01

Full Text Available The present review update the relationship between acetaldehyde and parkinsonism with a specific focus on the role of P450 system and CYP 2E1 isozyme particularly.We have indicated that acetaldehyde is able to enhance the parkinsonism induced in mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a neurotoxin able to damage the nigrostriatal dopaminergic pathway. Similarly diethyldithiocarbamate, the main metabolite of disulfiram, a drug widely used to control alcoholism, diallylsulfide and phenylisothiocyanate also markedly enhance the toxin-related parkinsonism. All these compounds are substrate/inhibitors of CYP450 2E1 isozyme. The presence of CYP 2E1 has been detected in the dopamine neurons of rodent Substantia Nigra, but a precise function of the enzyme has not been elucidated yet. By treating CYP 2E1 knockout mice with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, the Substantia Nigra induced lesion was significantly reduced when compared with the lesion observed in wild-type animals. Several in vivo and in vitro studies led to the conclusion that CYP 2E1 may enhance the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in mice by increasing free radical production inside the dopaminergic neurons. Acetaldehyde is a good substrate for CYP 2E1 enzyme as the other substrate-inhibitors and by this way may facilitate the susceptibility of dopaminergic neurons to toxic events. The literature suggests that ethanol and/or disulfiram may be responsible for toxic parkinsonism in human and it indicates that basal ganglia are the major targets of disulfiram toxicity. A very recent study reports that there are a decreased methylation of the CYP 2E1 gene and increased expression of CYP 2E1 mRNA in Parkinson’s Disease patient brains. This study suggests that epigenetic variants of this cytochrome contribute to the susceptibility, thus confirming multiples lines of evidence which indicate a link between environmental toxins and

Evidence supporting a role for TopBP1 and Brd4 in the initiation but not continuation of human papillomavirus 16 E1/E2-mediated DNA replication.

Science.gov (United States)

Gauson, Elaine J; Donaldson, Mary M; Dornan, Edward S; Wang, Xu; Bristol, Molly; Bodily, Jason M; Morgan, Iain M

2015-05-01

To replicate the double-stranded human papillomavirus 16 (HPV16) DNA genome, viral proteins E1 and E2 associate with the viral origin of replication, and E2 can also regulate transcription from adjacent promoters. E2 interacts with host proteins in order to regulate both transcription and replication; TopBP1 and Brd4 are cellular proteins that interact with HPV16 E2. Previous work with E2 mutants demonstrated the Brd4 requirement for the transactivation properties of E2, while TopBP1 is required for DNA replication induced by E2 from the viral origin of replication in association with E1. More-recent studies have also implicated Brd4 in the regulation of DNA replication by E2 and E1. Here, we demonstrate that both TopBP1 and Brd4 are present at the viral origin of replication and that interaction with E2 is required for optimal initiation of DNA replication. Both cellular proteins are present in E1-E2-containing nuclear foci, and the viral origin of replication is required for the efficient formation of these foci. Short hairpin RNA (shRNA) against either TopBP1 or Brd4 destroys the E1-E2 nuclear bodies but has no effect on E1-E2-mediated levels of DNA replication. An E2 mutation in the context of the complete HPV16 genome that compromises Brd4 interaction fails to efficiently establish episomes in primary human keratinocytes. Overall, the results suggest that interactions between TopBP1 and E2 and between Brd4 and E2 are required to correctly initiate DNA replication but are not required for continuing DNA replication, which may be mediated by alternative processes such as rolling circle amplification and/or homologous recombination. Human papillomavirus 16 (HPV16) is causative in many human cancers, including cervical and head and neck cancers, and is responsible for the annual deaths of hundreds of thousands of people worldwide. The current vaccine will save lives in future generations, but antivirals targeting HPV16 are required for the alleviation of disease

Sulfation of fulvestrant by human liver cytosols and recombinant SULT1A1 and SULT1E1

Directory of Open Access Journals (Sweden)

Edavana VK

2011-11-01

Full Text Available Vineetha Koroth Edavana1, Xinfeng Yu1, Ishwori B Dhakal1, Suzanne Williams1, Baitang Ning2, Ian T Cook3, David Caldwell1, Charles N Falany3, Susan Kadlubar11Division of Medical Genetics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 2Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR, USA; 3Department of Pharmacology, University of Alabama, Birmingham, AL, USAAbstract: Fulvestrant (Faslodex™ is a pure antiestrogen that is approved to treat hormone receptor-positive metastatic breast cancer in postmenopausal women. Previous studies have demonstrated that fulvestrant metabolism in humans involves cytochromes P450 and UDP-glucuronosyltransferases (UGTs. To date, fulvestrant sulfation has not been characterized. This study examined fulvestrant sulfation with nine recombinant sulfotransferases and found that only SULT1A1 and SULT1E1 displayed catalytic activity toward this substrate, with Km of 4.2 ± 0.99 and 0.2 ± 0.16 µM, respectively. In vitro assays of 104 human liver cytosols revealed marked individual variability that was highly correlated with β-naphthol sulfation (SULT1A1 diagnostic substrate; r = 0.98, P < 0.0001, but not with 17ß-estradiol sulfation (SULT1E1 diagnostic substrate; r = 0.16, P = 0.10. Fulvestrant sulfation was correlated with both SULT1A1*1/2 genotype (P value = 0.023 and copy number (P < 0.0001. These studies suggest that factors influencing SULT1A1/1E1 tissue expression and/or enzymatic activity could influence the efficacy of fulvestrant therapy.Keywords: fulvestrant, sulfotransferase, genotype, copy number

PENGEMBANGAN PORTAL E-LEARNING SMK NEGERI 1 MANGGIS

Directory of Open Access Journals (Sweden)

Luh Joni Erawati Dewi

2013-08-01

Full Text Available Portal E-learning SMK Negeri 1 Manggis adalah sebuah sistem yang dibuat untuk membantu serta mendukung proses pembelajaran baik pemberian materi maupun tugas secara online. Dengan adanya portal e-learning ini diharapkan dapat meningkatkan kadar interaksi pembelajaran antara peserta didik dengan guru karena memungkinkan terjadinya interaksi pembelajaran dari mana dan kapan saja. Selain itu, melatih siswa lebih mandiri dan aktif dalam mendapatkan ilmu pengetahuan, serta mempermudah penyimpanan materi pembelajaran. Perancangan sistem ini digambarkan dengan menggunakan DFD (data flow diagram dan diimplementasikan dengan menggunakan Adobe Dreamwaver sebagai editor, Adobe Photoshop  sebagi pengelola design, PHP sebagai script programing, dan MYSQL sebagai pengolah basis data.   Kata-kata kunci: portal, e-learning, SMK Negeri 1 Manggis

Polimorfismos GSTT1 e GSTM1 em indivíduos tabagistas com carcinoma espinocelular de cabeça e pescoço GSTT1 and GSTM1 polymorphism in cigarette smokers with head and neck squamous cell carcinoma

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Joice Matos Biselli

2006-10-01

Full Text Available A variabilidade em genes relacionados aos processos de ativação e detoxificação de carcinógenos pode interferir na suscetibilidade ao câncer. OBJETIVO: Investigar a relação entre os polimorfismos GSTT1 e GSTM1 nulos e o risco para o carcinoma espinocelular de cabeça e pescoço em indivíduos tabagistas. MATERIAL E MÉTODO: Este estudo caso-controle foi realizado na Faculdade de Medicina de São José do Rio Preto, Brasil. Foram avaliadas as freqüências dos genótipos nulos GSTT1 e GSTM1 por PCR multiplex em 60 pacientes com carcinoma espinocelular de cabeça e pescoço e 60 indivíduos sem a doença. RESULTADOS: A cavidade oral foi o sítio de tumor mais freqüente. O genótipo GSTT1 nulo foi encontrado em 33,3% dos pacientes e em 23,3% dos indivíduos controles (p=0,311. Os grupos caso e controle apresentaram freqüências do genótipo GSTM1 nulo de 35% e 48,3%, respectivamente (p=0,582. Não foram encontradas associações entre o hábito etilista e genótipos nulos GSTT1 e GSTM1 em ambos os grupos (valores de p>0,05. O gênero masculino e o hábito etilista foram prevalentes em ambos os grupos. CONCLUSÃO: Neste estudo não foi possível estabelecer uma correlação entre os genótipos nulos GSTT1 e GSTM1 e o carcinoma espinocelular de cabeça e pescoço em indivíduos tabagistas.Gene variability related to carcinogen activation and detoxification may interfere with susceptibility to head and neck cancer. AIM: To investigate the relation between GSTT1 and GSTM1 null polymorphisms and the risk of head and neck squamous cell carcinoma in cigarette smokers. MATERIAL AND METHOD: A case-control study conducted at the Sao Jose do Rio Preto Medical School, Brazil. GSTM1 and GSTT1 null genotype frequencies were evaluated by multiplex PCR in 45 cigarette smokers with head and neck squamous cell carcinomas and 45 cigarette smokers without this disease. RESULTS: The oral cavity was the most prevalent tumor site for squamous cell carcinoma

Helicity description of e+e- → qanti qg and e+e- → Qanti Q(1--) → ggg on and off the Z0: quark, gluon and beam polarization effects

International Nuclear Information System (INIS)

Schiller, D.H.; Koerner, J.G.

1981-07-01

We develop the helicity description for the processes e + e - → qanti qg and e + e - → Qanti Q(1 -- ) → ggg(γgg) in the purely electromagnetic case, in the γ-Z 0 interference region and on the Z 0 -pole. We present complete differential cross section formulas including beam, quark and gluon polarization effects. We also treat the corresponding processes e + e - → qanti qS and e + e - → Qanti Q(1 -- ) → SSS(γSS) involving scalar gluons. (orig.)

168/E online for UA1

CERN Multimedia

1983-01-01

Five 168/E processors and associated specialized interface hardware made an importartant contribution to the UA1 experiment. The processors provided an online event display facility, and also flagged candidate events. See Annual Report 1983 p. 75, and photo 8305815X, 8395813X. This photo shows the team including DD personnel and UA1 members. On the foreground left, is Michel Demoulin. On the background, 3rd from left, is Adolfo Fucci, last Sergio Cittolin.

Synthesis of (E-2,4-Dinitro-N-((2E,4E-4-phenyl-5-(pyrrolidin-1-ylpenta-2,4-dienylideneaniline

Directory of Open Access Journals (Sweden)

Mostafa Fesanghari

2009-07-01

Full Text Available (E-2,4-Dinitro-N-((2E,4E-4-phenyl-5-(pyrrolidin-1-ylpenta-2,4-dienylidene aniline dye was prepared in one pot by reaction of premade N-2,4-dinitrophenyl-3-phenylpyridinium chloride (DNPPC and pyrrolidine in absolute MeOH.

Physicochemical and biological characterization of 1E10 Anti-Idiotype vaccine

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Machado Yoan J

2011-11-01

Full Text Available Abstract Background 1E10 monoclonal antibody is a murine anti-idiotypic antibody that mimics N-glycolyl-GM3 gangliosides. This antibody has been tested as an anti-idiotypic cancer vaccine, adjuvated in Al(OH3, in several clinical trials for melanoma, breast, and lung cancer. During early clinical development this mAb was obtained in vivo from mice ascites fluid. Currently, the production process of 1E10 is being transferred from the in vivo to a bioreactor-based method. Results Here, we present a comprehensive molecular and immunological characterization of 1E10 produced by the two different production processes in order to determine the impact of the manufacturing process in vaccine performance. We observed differences in glycosylation pattern, charge heterogeneity and structural stability between in vivo-produced 1E10 and bioreactor-obtained 1E10. Interestingly, these modifications had no significant impact on the immune responses elicited in two different animal models. Conclusions Changes in 1E10 primary structure like glycosylation; asparagine deamidation and oxidation affected 1E10 structural stability but did not affect the immune response elicited in mice and chickens when compared to 1E10 produced in mice.

Nonsafety loads on glass 1E power sources, revisited

International Nuclear Information System (INIS)

Lewin, J.

1980-01-01

The supply of some nonsafety loads from class 1E power sources is allowed by industry standards (IEEE Standards 308 and 384) and by US Nuclear Regulatory Commission Regulatory Guides 1.32 and 1.75. This has been questioned as a possible source of degradation of the class 1E system, and this power deals with assessment of the effects of this practice on the reliability of the power supply for engineered safety features (ESF) systems

Human CYP2E1 mediates the formation of glycidamide from acrylamide

Energy Technology Data Exchange (ETDEWEB)

Settels, Eva; Appel, Klaus E. [Federal Institute for Risk Assessment, Center for Experimental Toxicology, Berlin (Germany); Bernauer, Ulrike; Gundert-Remy, Ursula [Federal Institute for Risk Assessment, Department of Safety of Substances and Preparations, Berlin (Germany); Palavinskas, Richard; Klaffke, Horst S. [Federal Institute for Risk Assessment, Center for Analytical Chemistry, Berlin (Germany)

2008-10-15

Regarding the cancer risk assessment of acrylamide (AA) it is of basic interest to know, as to what amount of the absorbed AA is metabolized to glycidamide (GA) in humans, compared to what has been observed in laboratory animals. GA is suspected of being the ultimate carcinogenic metabolite of AA. From experiments with CYP2E1-deficient mice it can be concluded that AA is metabolized to GA primarily by CYP2E1. We therefore examined whether CYP2E1 is involved in GA formation in non-rodent species with the focus on humans by using human CYP2E1 supersomes trademark, marmoset and human liver microsomes and in addition, genetically engineered V79 cells expressing human CYP2E1 (V79h2E1 cells). Special emphasis was placed on the analytical detection of GA, which was performed by gas chromatography/mass spectrometry. The results show that AA is metabolized to GA in human CYP2E1 supersomes trademark, in marmoset and human liver microsomes as well as in V79h2E1 cells. The activity of GA formation is highest in supersomes trademark; in human liver it is somewhat higher than in marmoset liver. A monoclonal CYP2E1 human selective antibody (MAB-2E1) and diethyldithiocarbamate (DDC) were used as specific inhibitors of CYP2E1. The generation of GA could be inhibited by MAB-2E1 to about 80% in V79h2E1 cells and to about 90% in human and marmoset liver microsomes. Also DDC led to an inhibition of about 95%. In conclusion, AA is metabolized to GA by human CYP2E1. Overall, the present work describes (1) the application and refinement of a sensitive methodology in order to determine low amounts of GA, (2) the applicability of genetically modified V79 cell lines in order to investigate specific questions concerning metabolism and (3) the involvement, for the first time, of human CYP2E1 in the formation of GA from AA. Further studies will compare the activities of GA formation in genetically engineered V79 cells expressing CYP2E1 from different species. (orig.)

Search in s channel for production of 1--2 MeV/c2 long-lived e+e- resonances

International Nuclear Information System (INIS)

Henderson, S.D.; Asoka-Kumar, P.; Greenberg, J.S.; Lynn, K.G.; McCorkle, S.; McDonough, J.; Phlips, B.F.; Weber, M.

1992-01-01

The search for s-channel production of light neutral particles coupled to e + e- has been extended by more than 3 orders of magnitude in lifetime beyond the region which is accessible to elastic e + e- scattering. The whole mass range 1500 approx-lt M X 0 approx-lt 1860 keV/c 2 suggested by the observation of anomalous e + e- pairs in heavy-ion collisions has been investigated. These measurements find no evidence for e + e- states within lifetime ranges (90% C.L.) of 1.4x10 -12 approx-lt τ approx-lt 4x10 -10 sec (J=0) and 1.4x10 -12 approx-lt τ approx-lt 6x10 -10 sec (J=1), assuming that the state does not break up by interacting within the target

E-selectina soluble en una población infanto-juvenil con diabetes tipo 1 Soluble E- selectin in children and adolescents with type 1 diabetes

Directory of Open Access Journals (Sweden)

Teresita del R. Carrizo

2008-06-01

Full Text Available El estado de hiperglucemia crónica en los pacientes diabéticos produce una agresión al endotelio vascular, conduciendo al desarrollo prematuro de ateroesclerosis. El objetivo de este trabajo fue determinar niveles de E-selectina soluble (sE-S en una población infanto-juvenil con diabetes tipo1 (DT1 y su relación con el control glucémico y el perfil lipídico. Se estudiaron 30 pacientes con DT1 (16 mujeres y 14 varones, de edades comprendidas entre 6 y 15 años, comparados con 20 sujetos controles. Se determinaron: sE-S, glucemia en ayunas, hemoglobina glicosilada (HbA1c, colesterol total (CT, HDL-C, LDL-C, no HDL-C y triglicéridos (TG. Los niveles de sE-S fueron 66% más altos en los diabéticos que en los sujetos controles (p = 0.0001. Los pacientes fueron agrupados en: diabéticos con buen control glucémico (DBCG, HbA1c 8%. La concentración de sE-S en DPCG y en DBCG fue: 111.3 ± 40.5 vs. 68.0 ± 11.3 ng/ml, respectivamente p = 0.02. En los diabéticos la incidencia de valores no deseables en el perfil lipídico fue: CT: 50%; HDL-C 14%; LDL-C 52%, no HDL-C 26.7% y TG 14%. La sE-S se correlacionó mejor con HbA1c (r = 0.53, p = 0.0001 que con la glucemia en ayunas (r = 0.36, p = 0.008 y CT (r = 0.36, p = 0.009. De los resultados obtenidos se sugiere que la sE-S es un marcador temprano de disfunción endotelial y de probable riesgo de aterosclerosis en pacientes infanto-juveniles con DT1.The chronic hyperglycemic state in diabetic patients produces an aggression to the vascular endothelium leading to a premature development of atherosclerosis. The objective of this paper was to determine the soluble E-selectin (sE-S levels in children with type 1 diabetes (DT1 and its relationship with glycemic control and lipid profile. Thirty patients with DT1, (16 girls and 14 boys, age between 6 and 15 years were studied, whose data were compared with 20 control subjects. In both groups sE-S was determined as well as fasting glycemia, glycosylated

E1A-dependent trans-activation of the human MYC promoter is mediated by the E2F factor

International Nuclear Information System (INIS)

Hiebert, S.W.; Lipp, M.; Nevins, J.R.

1989-01-01

E2F is a cellular transcription factor that binds to two sites in the adenovirus E2 promoter. Previous experiments have implicated E2F in the E1A-dependent transactivation of the E2 gene since levels of active E2F increase markedly during adenovirus infection in parallel with the increase in E2 transcription, and an E2F binding site can confer E1A inducibility to a heterologous promoter. Here the authors show that E2F binds to two sequence elements within the P2 promoter of the human MYC gene which are within a region that is critical for promoter activity. The MYC promoter can be trans-activated in an E1A-dependent manner and site-directed mutagenesis demonstrates that these E2F elements are essential for trans-activation. Finally, they also find that adenovirus infection of quiescent cells results in a stimulation of the endogenous MYC gene. They conclude that the activation of the E2F factor, which is likely responsible for the activation of viral E2 transcription, is also responsible for the E1A-dependent induction of MYC transcription

Characterization of hepatitis C virus recombinants with chimeric E1/E2 envelope proteins and identification of single amino acids in the E2 stem region important for entry

DEFF Research Database (Denmark)

Carlsen, Thomas H R; Scheel, Troels K H; Ramirez, Santseharay

2013-01-01

The hepatitis C virus (HCV) envelope proteins E1 and E2 play a key role in host cell entry and represent important targets for vaccine and drug development. Here, we characterized HCV recombinants with chimeric E1/E2 complexes in vitro. Using genotype 1a/2a JFH1-based recombinants expressing 1a....../release. Studies of E1/E2 heterodimerization showed no differences in intracellular E1/E2 interaction for chimeric constructs with or without E2 stem region mutations. Interestingly, the E2 stem region mutations allowed efficient entry, which was verified in 1a-E1/1b-E2 HCV pseudoparticle assays. A CD81 inhibition...

In situ activation of benzyl alcohols with XtalFluor-E: formation of 1,1-diarylmethanes and 1,1,1-triarylmethanes through Friedel-Crafts benzylation.

Science.gov (United States)

Desroches, Justine; Champagne, Pier Alexandre; Benhassine, Yasmine; Paquin, Jean-François

2015-02-28

The Friedel-Crafts benzylation of arenes using benzyl alcohols activated in situ with XtalFluor-E is described. A wide range of 1,1-diarylmethanes and 1,1,1-triarylmethanes were prepared under experimentally simple and mild conditions, without the need for a transition metal or a strong Lewis acid. Notably, the reactivity observed demonstrates the potential of XtalFluor-E to induce C-OH bond ionization and SN1 reactivity of benzylic alcohols.

On polarization parameters of spin-1 particles and anomalous couplings in e"+e"- → ZZ/Zγ

International Nuclear Information System (INIS)

Rahaman, Rafiqul; Singh, Ritesh K.

2016-01-01

We study the anomalous trilinear gauge couplings of Z and γ using a complete set of polarization asymmetries for the Z boson in e"+e"- → ZZ/Zγ processes with unpolarized initial beams. We use these polarization asymmetries, along with the cross section, to obtain a simultaneous limit on all the anomalous couplings using the Markov Chain Monte Carlo (MCMC) method. For an e"+e"- collider running at 500 GeV center-of-mass energy and 100 fb"-"1 of integrated luminosity the simultaneous limits on the anomalous couplings are 1-3 x 10"-"3. (orig.)

B1 Cell IgE Impedes Mast Cell-Mediated Enhancement of Parasite Expulsion through B2 IgE Blockade

Directory of Open Access Journals (Sweden)

Rebecca K. Martin

2018-02-01

Full Text Available Helminth infection is known for generating large amounts of poly-specific IgE. Here we demonstrate that innate-like B1 cells are responsible for this IgE production during infection with the nematode parasites Nippostrongylus brasiliensis and Heligmosomoides polygyrus bakeri. In vitro analysis of B1 cell immunoglobulin class switch recombination to IgE demonstrated a requirement for anti-CD40 and IL-4 that was further enhanced when IL-5 was added or when the B1 source was helminth infected mice. An IL-25-induced upregulation of IgE in B1 cells was also demonstrated. In T cell-reconstituted RAG1−/− mice, N. brasiliensis clearance was enhanced with the addition of B2 cells in an IgE-dependent manner. This enhanced clearance was impeded by reconstitution with IgE sufficient B1 cells. Mucosal mast cells mediated the B2 cell enhancement of clearance in the absence of B1 cells. The data support B1 cell IgE secretion as a regulatory response exploited by the helminth.

Neutronic analysis of the 1D and 1E banks reflux detection system

Energy Technology Data Exchange (ETDEWEB)

Blanchard, A.

1999-12-21

Two H Canyon neutron monitoring systems for early detection of postulated abnormal reflux conditions in the Second Uranium Cycle 1E and 1D Mixer-Settle Banks have been designed and built. Monte Carlo neutron transport simulations using the general purpose, general geometry, n-particle MCNP code have been performed to model expected response of the monitoring systems to varying conditions.The confirmatory studies documented herein conclude that the 1E and 1D neutron monitoring systems are able to achieve adequate neutron count rates for various neutron source and detector configurations, thereby eliminating excessive integration count time. Neutron count rate sensitivity studies are also performed. Conversely, the transport studies concluded that the neutron count rates are statistically insensitive to nitric acid content in the aqueous region and to the transition region length. These studies conclude that the 1E and 1D neutron monitoring systems are able to predict the postulated reflux conditions for all examined perturbations in the neutron source and detector configurations. In the cases examined, the relative change in the neutron count rates due to postulated transitions from normal {sup 235}U concentration levels to reflux levels remain satisfactory detectable.

Neutronic analysis of the 1D and 1E banks reflux detection system

International Nuclear Information System (INIS)

Blanchard, A.

1999-01-01

Two H Canyon neutron monitoring systems for early detection of postulated abnormal reflux conditions in the Second Uranium Cycle 1E and 1D Mixer-Settle Banks have been designed and built. Monte Carlo neutron transport simulations using the general purpose, general geometry, n-particle MCNP code have been performed to model expected response of the monitoring systems to varying conditions.The confirmatory studies documented herein conclude that the 1E and 1D neutron monitoring systems are able to achieve adequate neutron count rates for various neutron source and detector configurations, thereby eliminating excessive integration count time. Neutron count rate sensitivity studies are also performed. Conversely, the transport studies concluded that the neutron count rates are statistically insensitive to nitric acid content in the aqueous region and to the transition region length. These studies conclude that the 1E and 1D neutron monitoring systems are able to predict the postulated reflux conditions for all examined perturbations in the neutron source and detector configurations. In the cases examined, the relative change in the neutron count rates due to postulated transitions from normal 235 U concentration levels to reflux levels remain satisfactory detectable

E2F-1-Induced p53-independent apoptosis in transgenic mice

DEFF Research Database (Denmark)

Holmberg, Christian Henrik; Helin, K.; Sehested, M.

1998-01-01

The E2F transcription factors are key targets for the retinoblastoma protein, pRB. By inactivation of E2Fs, pRB prevents progression to the S phase. To test proliferative functions of E2F, we generated transgenic mice expressing human E2F-1 and/or human DP-1. When the hydroxymethyl glutaryl...... involving increased apoptosis in the germinal epithelium. This effect was potentiated by simultaneous overexpression of DP-1. Testicular atrophy as a result of overexpression of E2F-1 and DP-1 is independent of functional p53, since p53-nullizygous transgenic mice overexpressing E2F-1 and DP-1 also suffered...

Regulation of eukaryotic elongation factor 1 alpha (eEF1A) by dynamic lysine methylation

DEFF Research Database (Denmark)

Jakobsson, Magnus E; Małecki, Jędrzej; Falnes, Pål Ø

2018-01-01

Lysine methylation is a frequent post-translational protein modification, which has been intensively studied in the case of histone proteins. Lysine methylations are also found on many non-histone proteins, and one prominent example is eukaryotic elongation factor 1 alpha (eEF1A). Besides its...... essential role in the protein synthesis machinery, a number of non-canonical functions have also been described for eEF1A, such as regulation of the actin cytoskeleton and the promotion of viral replication. The functional significance of the extensive lysine methylations on eEF1A, as well as the identity...

RIGOROUS PHOTOGRAMMETRIC PROCESSING OF CHANG'E-1 AND CHANG'E-2 STEREO IMAGERY FOR LUNAR TOPOGRAPHIC MAPPING

OpenAIRE

K. Di; Y. Liu; B. Liu; M. Peng

2012-01-01

Chang'E-1(CE-1) and Chang'E-2(CE-2) are the two lunar orbiters of China's lunar exploration program. Topographic mapping using CE-1 and CE-2 images is of great importance for scientific research as well as for preparation of landing and surface operation of Chang'E-3 lunar rover. In this research, we developed rigorous sensor models of CE-1 and CE-2 CCD cameras based on push-broom imaging principle with interior and exterior orientation parameters. Based on the rigorous sensor model, the 3D c...

Identification and analysis of e{sup +}e{sup -}-pairs in C+C collisions at 1 AGeV; Identifikation und Analyse von e{sup +}e{sup -}-Paaren in C+C Stoessen bei 1 AGeV

Energy Technology Data Exchange (ETDEWEB)

Christ, T.

2007-10-22

The object of this thesis is the analysis of the data that have be recorded with HADES for the system {sup 12}C+{sup 12}C at a beam energy of E=1 AGeV. Within this work a probabilistic algorithm for efficient e{sup +}/e{sup -} identification and hadron suppression has been developed and integrated into the HADES analysis software. The method has been tested with extensive simulations and achieves an identification efficiency above 95% for momenta below p=600 MeV/c. Hadronic background in the e{sup +}/e{sup -}-sample up to p=600 MeV/c is reduced to less than 2%. For larger momenta the contamination with charged pions remains below 5%, for protons at polar angles below 44 it does not exceed 14%. After combination of the identified e{sup +}/e{sup -}-trajectories into pairs und subtraction of the combinatorial background there remains a physics signal of 47687{+-}1528 e{sup +}e{sup -}-pairs, for which distributions of invariant mass, transverse momentum and rapidity are determined. The signal-to-background ratio S/B for pair masses between 80 und 450 MeV/c{sup 2} is between 0.2 und 1. By applying further cuts upon the pair-sample the background induced by leptons from conversion processes is reduced substantially. After all cuts 11000{+-}432 e{sup +}e{sup -}-pairs remain. For M{sub e{sup +}}{sub e{sup -}} > 200 MeV/c{sup 2} S/B rises exponentially from about 2 to values of up to 10. The systematic error of the analysis for pairs with masses below 150 MeV/c{sup 2} is determined to be 17.5%, for higher masses a value of 23% is found. For transverse momentum and rapidity one finds below (above) M{sub e{sup +}}{sub e{sup -}}=150 MeV/c{sup 2} systematic errors of 17.5% (21.4%) and 15.3% (33.5%) respectively. Together with e{sup +}e{sup -} multiplicities published by HADES for the system {sup 12}C+{sup 12}C at E=2 AGeV the excitation function of the excess-multiplicity is determined from the measurement results. (orig.)

IgE epitopes of intact and digested Ara h 1

DEFF Research Database (Denmark)

Bøgh, Katrine Lindholm; Nielsen, H.; Madsen, Charlotte Bernhard

2012-01-01

epitopes have been suggested to be of great importance. ObjectiveThe aim of this study was to identify IgE specific epitopes of intact and digested Ara h 1, and to compare epitope patterns between humans and rats. MethodsSera from five peanut allergic patients and five Brown Norway rats were used...... to identify intact and digested Ara h 1-specific IgE epitopes by competitive immunoscreening of a phage-displayed random hepta-mer peptide library using polyclonal IgE from the individual sera. The resulting peptide sequences were mapped on the surface of a three-dimensional structure of the Ara h 1 molecule...... to mimic epitopes using a computer-based algorithm. ResultsPatients as well as rats were shown to have individual IgE epitope patterns. All epitope mimics were conformational and found to cluster into three different areas of the Ara h 1 molecule. Five epitope motifs were identified by patient IgE, which...

Análise comparativa entre galectinas-1 humana e de camundongo sob os aspectos biológico e molecular

OpenAIRE

Amanda Cristina Trabuco

2013-01-01

A galectina-1 (Gal-1) é uma lectina homodimérica multifuncional capaz de reconhecer e se ligar a beta-galactosídeos por meio de um domínio denominado carbohydrate recognition domain (CRD). A Gal-1 humana (Gal-1h) e a Gal-1 de camundongo (Gal-1c) mantêm 88,15% de homologia e, apesar de não existirem mutações em aminoácidos-chave do CRD, há substituições próximas a esses resíduos. Considerando as implicações dessas diferenças em estrutura e função, e que é comum a utilização de modelos murinos ...

UA1 experience with 3081/E systems

International Nuclear Information System (INIS)

Sphicas, P.A.

1987-01-01

A Harvard/MIT collaboration has built, with support from CERN, a 3081/E farm of two processors in Cambridge, MA. The farm was completed in the beginning of 1986. It has since been used for UA1 data analysis and two full production runs have been completed so far. The system will be upgraded in the near future: the number of 3081/E's will be increased to five, and a new IBM-VME interface developed at CERN will be installed. Similar farms have either already been built (CERN, 5 emulators) or have received approval (ROME, 2 emulators). They will also be used for production and analysis of UA1 data. An overview of the status, performance and future of these systems will be given. (orig.)

Pressure-induced magnetic collapse and metallization of TlF e1.6S e2

Science.gov (United States)

Naumov, P. G.; Filsinger, K.; Shylin, S. I.; Barkalov, O. I.; Ksenofontov, V.; Qi, Y.; Palasyuk, T.; Schnelle, W.; Medvedev, S. A.; Greenblatt, M.; Felser, C.

2017-08-01

The crystal structure, magnetic ordering, and electrical resistivity of TlF e1.6S e2 were studied at high pressures. Below ˜7 GPa , TlF e1.6S e2 is an antiferromagnetically ordered semiconductor with a ThC r2S i2 -type structure. The insulator-to-metal transformation observed at a pressure of ˜7 GPa is accompanied by a loss of magnetic ordering and an isostructural phase transition. In the pressure range ˜7.5 -11 GPa a remarkable downturn in resistivity, which resembles a superconducting transition, is observed below 15 K. We discuss this feature as the possible onset of superconductivity originating from a phase separation in a small fraction of the sample in the vicinity of the magnetic transition.

Epicteto: Diatribes 1.29 e 1.30 - uma síntese da filosofia epictetiana das Diatribes

Directory of Open Access Journals (Sweden)

Aldo Dinucci

2015-04-01

Full Text Available As diatribes 1.29 e 1.30 encerram o livro primeiro das Diatribes de Epicteto e nos oferecem uma síntese da filosofia de Epicteto. Em 1.29.1, Epicteto nos diz que a essência (ousia do bem do ser humano “é uma capacidade de escolha de certa qualidade”, isto é, a escolha disposta de certa maneira. Por essa definição, todas as demais coisas que se encontram fora do âmbito da escolha e, consequentemente, do bem humano são somente materiais para a escolha (1.29.2, a partir dos quais ela construirá seu próprio bem ou seu próprio mal. Temos aí posta de outra forma a distinção entre coisas sob nosso encargo e coisas que não estão sob nosso encargo (eph’hemin kai ouk eph’hemin, sobre qual Epicteto trata detidamente em diatribe 1.1 e no primeiro capítulo do Encheirídion

40 CFR 721.4575 - L-aspartic acid, N,N′- [(1E) - 1,2 - ethenediylbis[(3-sulfo-4, 1-phenylene)imino [6-(phenylamino...

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false L-aspartic acid, N,Nâ²- [(1E) - 1,2... Substances § 721.4575 L-aspartic acid, N,N′- [(1E) - 1,2 - ethenediylbis[(3-sulfo-4, 1-phenylene)imino [6... uses subject to reporting. (1) The chemical substance identified as l-aspartic acid, N,N′- [(1E) - 1,2...

Efficacy of a gE-deleted, bovine herpesvirus 1 (BoHV-1 inactivated vaccine Eficácia de uma vacina inativada, gE-deletada, contra o herpesvírus bovino tipo 1 (BoHV-1

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Alessandra D. Silva

2009-07-01

Full Text Available Bovine herpesvirus type 1 (BoHV-1 is recognized as a major cause of economic losses in cattle. Vaccination has been widely applied to minimize losses induced by BoHV-1 infections. We have previously reported the development of a differential BoHV-1 vaccine, based on a recombinant glycoprotein E (gE-deleted virus (265gE-. In present paper the efficacy of such recombinant was evaluated as an inactivated vaccine. Five BoHV-1 seronegative calves were vaccinated intramuscularly on day 0 and boostered 30 days later with an inactivated, oil adjuvanted vaccine containing an antigenic mass equivalent to 10(7.0 fifty per cent cell culture infectious doses (CCID50 of 265gE-. Three calves were kept as non vaccinated controls. On day 60 post vaccination both vaccinated and controls were challenged with the virulent parental strain. No clinical signs or adverse effects were seen after or during vaccination. After challenge, 2/5 vaccinated calves showed mild clinical signs of infection, whereas all non vaccinated controls displayed intense rhinotracheitis and shed virus for longer and to higher titres than vaccinated calves. Serological responses were detected in all vaccinated animals after the second dose of vaccine, but not on control calves. Following corticosteroid administration in attempting to induce reactivation of the latent infection, no clinical signs were observed in vaccinated calves, whereas non vaccinated controls showed clinical signs of respiratory disease. In view of its immunogenicity and protective effect upon challenge with a virulent BoHV-1, the oil adjuvanted preparation with the inactivated 265gE- recombinant was shown to be suitable for use as a vaccine.O Herpesvírus bovino tipo 1 (BoHV-1 é reconhecido como um importante agente de perdas econômicas em bovinos. Vacinação tem sido amplamente empregada para minimizar as perdas conseqüentes a infecções com o BoHV-1. Reportamos previamente o desenvolvimento de uma vacina

Incidência de fumonisina B1, aflatoxinas B1, B2, G1 e G2, ocratoxina A e zearalenona em produtos de milho Occurrence of fumonisin B1, aflatoxins B1, B2, G1, and G2, ochratoxin A and zearalenone in corn products

Directory of Open Access Journals (Sweden)

Luciane Mie Kawashima

2006-09-01

Full Text Available Levantamentos de ocorrência de micotoxinas em alimentos foram realizados nas últimas duas décadas nas regiões Sudeste e Sul do Brasil. Levantamentos em alimentos comercializados em outras regiões têm-se limitado a aflatoxinas em amendoim e castanhas do Brasil. O presente trabalho pesquisou a presença de fumonisina B1, aflatoxinas B1, B2, G1 e G2, ocratoxina A e zearalenona em 74 amostras de produtos a base de milho adquiridas no comércio da cidade de Recife, PE, durante o período de 1999 a 2001. Fumonisina B1 foi determinada por cromatografia líquida de alta eficiência com detecção por fluorescência e as demais toxinas foram determinadas por cromatografia em camada delgada. Fumonisina B1 foi encontrada em 94,6% das amostras em concentrações variando de 20 a 8600 µg/kg. Apenas 5 amostras continham aflatoxina B1 e o teor máximo encontrado foi 20 µg/kg. Duas amostras ultrapassaram o limite de 20 µg/kg para a somatória das aflatoxinas B1, B2, G1 e G2 (farinha de milho pré-cozida com 21,5 µg/kg e quirera (xerém com 23,3 µg/kg. As aflatoxinas G1 e G2, ocratoxina A e zearalenona não foram detectadas em nenhuma das amostras. Todas as amostras contaminadas com aflatoxinas também apresentaram fumonisina B1.Research concerning the presence of mycotoxin in food has been conducted in the Southwest and South regions of Brazil over the last two decades. Research in other regions has been limited to aflatoxin in peanuts and Brazil nuts. The aim of this work is to study the presence of fumonisin B1, aflatoxins B1, B2, G1, and G2, ochratoxin A and zearalenone in 74 samples of corn products acquired in shops and food markets in the city of Recife (PE from 1999 to 2001. Fumonisin B1 was determined by high performance liquid chromatography and fluorescence was detected. The other toxins were determined by thin layer chromatography. Fumonisin B1 was found in 94.6% of the samples in levels from 20 to 8600 µg/kg. Only 5 samples contained

E2F1-mediated transcriptional inhibition of the plasminogen activator inhibitor type 1 gene

DEFF Research Database (Denmark)

Koziczak, M; Müller, H; Helin, K

2001-01-01

but independent of binding to pocket-binding proteins, suggesting a novel mechanism for E2F-mediated negative gene regulation [Koziczak, M., Krek, W. & Nagamine, Y. (2000) Mol. Cell. Biol. 20, 2014-2022]. However, it remains to be seen whether endogenous E2F can exert a similar effect. We report here that down....... These results all indicate that endogenous E2F can directly repress the PAI-1 gene. DNase I hypersensitive-site analysis of the PAI-1 promoter suggested the involvement of conformation changes in chromatin structure of the PAI-1 promoter. 5' deletion analysis of the PAI-1 promoter showed that multiple sites...

Rac1 activation inhibits E-cadherin-mediated adherens junctions via binding to IQGAP1 in pancreatic carcinoma cells

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Giehl Klaudia

2009-09-01

Full Text Available Abstract Background Monomeric GTPases of the Rho family control a variety of cellular functions including actin cytoskeleton organisation, cell migration and cell adhesion. Defects in these regulatory processes are involved in tumour progression and metastasis. The development of metastatic carcinoma is accompanied by deregulation of adherens junctions, which are composed of E-cadherin/β- and α-catenin complexes. Results Here, we show that the activity of the monomeric GTPase Rac1 contributes to inhibition of E-cadherin-mediated cell-cell adhesion in pancreatic carcinoma cells. Stable expression of constitutively active Rac1(V12 reduced the amount of E-cadherin on protein level in PANC-1 pancreatic carcinoma cells, whereas expression of dominant negative Rac1(N17 resulted in an increased amount of E-cadherin. Extraction of proteins associated with the actin cytoskeleton as well as coimmunoprecipitation analyses demonstrated markedly decreased amounts of E-cadherin/catenin complexes in Rac1(V12-expressing cells, but increased amounts of functional E-cadherin/catenin complexes in cells expressing Rac1(N17. Cell aggregation and migration assays revealed, that cells containing less E-cadherin due to expression of Rac1(V12, exhibited reduced cell-cell adhesion and increased cell motility. The Rac/Cdc42 effector protein IQGAP1 has been implicated in regulating cell-cell adhesion. Coimmunoprecipitation studies showed a decrease in the association between IQGAP1 and β-catenin in Rac1(V12-expressing PANC-1 cells and an association of IQGAP1 with Rac1(V12. Elevated association of IQGAP1 with the E-cadherin adhesion complex via β-catenin correlated with increased intercellular adhesion of PANC-1 cells. Conclusion These results indicate that active Rac1 destabilises E-cadherin-mediated cell-cell adhesion in pancreatic carcinoma cells by interacting with IQGAP1 which is associated with a disassembly of E-cadherin-mediated adherens junctions. Inhibition

E4orf1 Enhances Glucose Uptake Independent of Proximal Insulin Signaling.

Science.gov (United States)

Na, Ha-Na; Hegde, Vijay; Dubuisson, Olga; Dhurandhar, Nikhil V

2016-01-01

Impaired proximal insulin signaling is often present in diabetes. Hence, approaches to enhance glucose disposal independent of proximal insulin signaling are desirable. Evidence indicates that Adenovirus-derived E4orf1 protein may offer such an approach. This study determined if E4orf1 improves insulin sensitivity and downregulates proximal insulin signaling in vivo and enhances cellular glucose uptake independent of proximal insulin signaling in vitro. High fat fed mice were injected with a retrovirus plasmid expressing E4orf1, or a null vector. E4orf1 significantly improved insulin sensitivity in response to a glucose load. Yet, their proximal insulin signaling in fat depots was impaired, as indicated by reduced tyrosine phosphorylation of insulin receptor (IR), and significantly increased abundance of ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1). In 3T3-L1 pre-adipocytes E4orf1 expression impaired proximal insulin signaling. Whereas, treatment with rosiglitazone reduced ENPP1 abundance. Unaffected by IR-KD (insulin receptor knockdown) with siRNA, E4orf1 significantly up-regulated distal insulin signaling pathway and enhanced cellular glucose uptake. In vivo, E4orf1 impairs proximal insulin signaling in fat depots yet improves glycemic control. This is probably explained by the ability of E4orf1 to promote cellular glucose uptake independent of proximal insulin signaling. E4orf1 may provide a therapeutic template to enhance glucose disposal in the presence of impaired proximal insulin signaling.

E4orf1 Enhances Glucose Uptake Independent of Proximal Insulin Signaling.

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Ha-Na Na

Full Text Available Impaired proximal insulin signaling is often present in diabetes. Hence, approaches to enhance glucose disposal independent of proximal insulin signaling are desirable. Evidence indicates that Adenovirus-derived E4orf1 protein may offer such an approach. This study determined if E4orf1 improves insulin sensitivity and downregulates proximal insulin signaling in vivo and enhances cellular glucose uptake independent of proximal insulin signaling in vitro. High fat fed mice were injected with a retrovirus plasmid expressing E4orf1, or a null vector. E4orf1 significantly improved insulin sensitivity in response to a glucose load. Yet, their proximal insulin signaling in fat depots was impaired, as indicated by reduced tyrosine phosphorylation of insulin receptor (IR, and significantly increased abundance of ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1. In 3T3-L1 pre-adipocytes E4orf1 expression impaired proximal insulin signaling. Whereas, treatment with rosiglitazone reduced ENPP1 abundance. Unaffected by IR-KD (insulin receptor knockdown with siRNA, E4orf1 significantly up-regulated distal insulin signaling pathway and enhanced cellular glucose uptake. In vivo, E4orf1 impairs proximal insulin signaling in fat depots yet improves glycemic control. This is probably explained by the ability of E4orf1 to promote cellular glucose uptake independent of proximal insulin signaling. E4orf1 may provide a therapeutic template to enhance glucose disposal in the presence of impaired proximal insulin signaling.

Rates of E1, E2, M1, and M2 transitions in Ni II

Science.gov (United States)

Cassidy, C. M.; Hibbert, A.; Ramsbottom, C. A.

2016-03-01

Aims: We present rates for all E1, E2, M1, and M2 transitions among the 295 fine-structure levels of the configurations 3d9, 3d84s, 3d74s2, 3d84p, and 3d74s4p, determined through an extensive configuration interaction calculation. Methods: The CIV3 code developed by Hibbert and coworkers is used to determine for these levels configuration interaction wave functions with relativistic effects introduced through the Breit-Pauli approximation. Results: Two different sets of calculations have been undertaken with different 3d and 4d functions to ascertain the effect of such variation. The main body of the text includes a representative selection of data, chosen so that key points can be discussed. Some analysis to assess the accuracy of the present data has been undertaken, including comparison with earlier calculations and the more limited range of experimental determinations. The full set of transition data is given in the supplementary material as it is very extensive. Conclusions: We believe that the present transition data are the best currently available. Full Table 4 and Tables 5-8 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/587/A107

Structural and electrochemical studies of TiO2 complexes with (4,4'-((1E,1'E)-(2,5-bis(octyloxy)-1,4-phenylene)bis(ethene-2,1-diyl))bis-(E)-N-(2,5-bis(octyloxy)benzylidene)) imine derivative bases towards organic devices.

Science.gov (United States)

Rozycka, Anna; Iwan, Agnieszka; Bogdanowicz, Krzysztof Artur; Filapek, Michal; Górska, Natalia; Hreniak, Agnieszka; Marzec, Monika

2018-06-12

Three (4,4'-((1E,1'E)-(2,5-bis(octyloxy)-1,4-phenylene)bis(ethene-2,1-diyl))bis-(E)-N-(2,5-bis(octyloxy)benzylidene)) imine derivatives were synthesized via a condensation reaction with p-toluenesulfonic acid as a catalyst. The effects of the end groups and vinylene (-HC[double bond, length as m-dash]CH-) moieties on the structural, thermal, optical, electrochemical and photovoltaic properties of imines were investigated to check the influence of TiO2 on the imine properties. The thermal behavior of imines and their complexes with TiO2 was widely investigated using FT-IR, XRD, DSC and POM methods in order to determine the order type in the imine structure. All imines present the highest occupied molecular orbital (HOMO) levels of about -5.39 eV (SAI1 and SAI2) and -5.27 eV (SAI3) and the lowest unoccupied molecular orbital (LUMO) levels at about -3.17 eV. The difference of the end groups in the imines in each case did not affect redox properties. Generally, both oxidation and reduction are easier after TiO2 addition and it also changes the HOMO-LUMO levels of imines. Moreover, changes in the characteristic bands for imines in the region 1500-1700 cm-1 observed as a drastic decrease of intensity or even disappearance of bands in the imine : TiO2 mixture suggest the formation of a complex (C[double bond, length as m-dash]N)-TiO2. Organic devices with the configuration of ITO/TiO2/SAIx (or SAIx : TiO2)/Au were fabricated and investigated in the presence and absence of visible light irradiation with an intensity of 93 mW cm-2. In all imines and complexes with TiO2, the generation of the photocurrent indicates their use as photodiodes and the best result was observed for SAI3 : TiO2 complexes.

Research of quality control during development of NPP DCS 1E classified software

International Nuclear Information System (INIS)

Shi Weihua; Lu Zhenguo; Xie Qi

2012-01-01

The Nuclear safety depends on right behavior of 1E software, which is a important part of 1E DCS system. Nowadays, user focus on good function of 1E system, but pay little attention to quality control of 1E software. In fact, it's declared in IEC61513 and IEC60880 that 1E software should under strict quality control during all stages of development. This article is related to the practice of 1E DCS system quality control and explores the QC surveillance for 1E software from the user's point of view. (authors)

E3B1/ABI-1 Isoforms Are Down-Regulated in Cancers of Human Gastrointestinal Tract

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Rafia A. Baba

2012-01-01

Full Text Available The expression of E3B1/ABI-1 protein and its role in cancer progression and prognosis are largely unknown in the majority of solid tumors. In this study, we examined the expression pattern of E3B1/ABI-1 protein in histologically confirmed cases of esophageal (squamous cell carcinoma and adenocarcinoma, gastro-esophageal junction, colorectal cancers and corresponding normal tissues freshly resected from a cohort of 135 patients, by Western Blotting and Immunofluorescence Staining. The protein is present in its phosphorylated form in cells and tissues. Depending on the extent of phosphorylation it is either present in hyper-phosphorylated (M. Wt. 72 kDa form or in hypo-phosphorylated form (M. Wt. 68 kDa and 65 kDa. A thorough analysis revealed that expression of E3B1/ABI-1 protein is significantly decreased in esophageal, gastro-esophageal junction and colorectal carcinomas irrespective of age, gender, dietary and smoking habits of the patients. The decrease in expression of E3B1/ABI-1 was consistently observed for all the three isoforms. However, the decrease in the expression of isoforms varied with different forms of cancers. Down-regulation of E3B1/ABI-1 expression in human carcinomas may play a critical role in tumor progression and in determining disease prognosis.

Three closely related (2E,2′E-3,3′-(1,4-phenylenebis[1-(methoxyphenylprop-2-en-1-ones]: supramolecular assemblies in one dimension mediated by hydrogen bonding and C—H...π interactions

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Aijia Sim

2017-06-01

Full Text Available In the title compounds, (2E,2′E-3,3′-(1,4-phenylenebis[1-(2-methoxyphenylprop-2-en-1-one], C26H22O4 (I, (2E,2′E-3,3′-(1,4-phenylenebis[1-(3-methoxyphenylprop-2-en-1-one], C26H22O4 (II and (2E,2′E-3,3′-(1,4-phenylenebis[1-(3,4-dimethoxyphenylprop-2-en-1-one], C28H26O6 (III, the asymmetric unit consists of a half-molecule, completed by crystallographic inversion symmetry. The dihedral angles between the central and terminal benzene rings are 56.98 (8, 7.74 (7 and 7.73 (7° for (I, (II and (III, respectively. In the crystal of (I, molecules are linked by pairs of C—H...π interactions into chains running parallel to [101]. The packing for (II and (III, features inversion dimers linked by pairs of C—H...O hydrogen bonds, forming R22(16 and R22(14 ring motifs, respectively, as parts of [201] and [101] chains, respectively.

26 CFR 31.3302(e)-1 - Successor employer.

Science.gov (United States)

2010-04-01

..., acquired by the taxpayer. Example. In April 1961 the X Partnership terminated after selling all of its... under section 3302(e). (d) Cross-references. See paragraph (b) of § 31.3306(b)(1)-1 for examples of the...

Search for high-mass e+e- resonances in pp collisions at sqrt[s]=1.96 TeV.

Science.gov (United States)

Aaltonen, T; Adelman, J; Akimoto, T; Albrow, M G; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Apresyan, A; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzurri, P; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Beecher, D; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Beringer, J; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burke, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Calancha, C; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Chwalek, T; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Compostella, G; Convery, M E; Conway, J; Cordelli, M; Cortiana, G; Cox, C A; Cox, D J; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Dagenhart, D; Datta, M; Davies, T; de Barbaro, P; De Cecco, S; Deisher, A; De Lorenzo, G; Dell'Orso, M; Deluca, C; Demortier, L; Deng, J; Deninno, M; Derwent, P F; di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Elagin, A; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Frank, M J; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garberson, F; Garcia, J E; Garfinkel, A F; Genser, K; Gerberich, H; Gerdes, D; Gessler, A; Giagu, S; Giakoumopoulou, V; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C M; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Han, B-Y; Han, J Y; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hays, C; Heck, M; Heijboer, A; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hewamanage, S; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jayatilaka, B; Jeon, E J; Jha, M K; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Kar, D; Karchin, P E; Kato, Y; Kephart, R; Keung, J; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, H W; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kreps, M; Kroll, J; Krop, D; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhr, T; Kulkarni, N P; Kurata, M; Kusakabe, Y; Kwang, S; Laasanen, A T; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, E; Lee, H S; Lee, S W; Leone, S; Lewis, J D; Lin, C-S; Linacre, J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, C; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lovas, L; Lucchesi, D; Luci, C; Lueck, J; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Macqueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis-Katsikakis, A; Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Mathis, M; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzione, A; Merkel, P; Mesropian, C; Miao, T; Miladinovic, N; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moggi, N; Moon, C S; Moore, R; Morello, M J; Morlok, J; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Nett, J; Neu, C; Neubauer, M S; Neubauer, S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Griso, S Pagan; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Peiffer, T; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Pianori, E; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Pueschel, E; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Rekovic, V; Renton, P; Renz, M; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rodriguez, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Safonov, A; Sakumoto, W K; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savoy-Navarro, A; Schlabach, P; Schmidt, A; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sforza, F; Sfyrla, A; Shalhout, S Z; Shears, T; Shepard, P F; Shimojima, M; Shiraishi, S; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spreitzer, T; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Strycker, G L; Stuart, D; Suh, J S; Sukhanov, A; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thompson, G A; Thomson, E; Tipton, P; Ttito-Guzmán, P; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Tourneur, S; Trovato, M; Tsai, S-Y; Tu, Y; Turini, N; Ukegawa, F; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Veszpremi, V; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Volobouev, I; Volpi, G; Wagner, P; Wagner, R G; Wagner, R L; Wagner, W; Wagner-Kuhr, J; Wakisaka, T; Wallny, R; Wang, C; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Weinelt, J; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Wilbur, S; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Würthwein, F; Wynne, S M; Xie, S; Yagil, A; Yamamoto, K; Yamaoka, J; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zhang, X; Zheng, Y; Zucchelli, S

2009-01-23

A search for high-mass resonances in the e+e- final state is presented based on 2.5 fb(-1) of sqrt[s]=1.96 TeV pp collision data from the CDF II detector at the Fermilab Tevatron. The largest excess over the standard model prediction is at an e+e- invariant mass of 240 GeV/c2. The probability of observing such an excess arising from fluctuations in the standard model anywhere in the mass range of 150-1000 GeV/c2 is 0.6% (equivalent to 2.5sigma). We exclude the standard model coupling Z' and the Randall-Sundrum graviton for k/MPl=0.1 with masses below 963 and 848 GeV/c2 at the 95% credibility level, respectively.

Forbidden Raman scattering processes. I. General considerations and E1--M1 scattering

International Nuclear Information System (INIS)

Harney, R.C.

1979-01-01

The generalized theory of forbidden Raman scattering processes is developed in terms of the multipole expansion of the electromagnetic interaction Hamiltonian. Using the general expressions, the theory of electric dipole--magnetic dipole (E1--M1) Raman scattering is derived in detail. The 1 S 0 → 3 P 1 E1--M1 Raman scattering cross section in atomic magnesium is calculated for two applicable laser wavelengths using published f-value data. Since resonantly enhanced cross sections larger than 10 -29 cm 2 /sr are predicted it should be possible to experimentally observe this scattering phenomenon. In addition, by measuring the frequency dependence of the cross section near resonance, it may be possible to directly determine the relative magnitudes of the Axp and AxA contributions to the scattering cross section. Finally, possible applications of the effect in atomic and molecular physics are discussed

Shell effects on the E1 moments of Ra-Th nuclei

International Nuclear Information System (INIS)

Leander, G.A.

1984-01-01

Large systematic shell effects on intrinsic E1 moments are found, which should modulate any E1 moment induced by β 3 deformation. The calculated shell effects can explain an emerging trend for E1 data in Ra-Th nuclei, if and only if the gross β 3 -induced polarization of finite nuclear matter goes in the same direction as the lightning rod effect. 16 references

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...

A novel technique with enhanced detection and quantitation of HPV-16 E1- and E2-mediated DNA replication

International Nuclear Information System (INIS)

Taylor, Ewan R.; Morgan, Iain M.

2003-01-01

Transient DNA replication assays to detect papillomavirus E1/E2-mediated DNA replication have depended upon Southern blotting. This technique is hazardous (radioactive), labour intensive, semiquantitative, and physically limited in the number of samples that can be processed at any one time. We have overcome these problems by developing a real-time PCR protocol for the detection of E1/E2-mediated transient DNA replication. The results demonstrate detection of replication at levels not seen using Southern blotting demonstrating enhanced sensitivity. This technique is also, by definition, highly quantitative. Therefore, the real-time PCR technique is the optimal method for the detection of E1/E2-mediated DNA replication

Thermal decomposition of vinyl- and allylsilane platinum(II complexes and platinum(II catalysed synthesis of (E,(E-1,4-diphenyl-1,3-butadiene

Directory of Open Access Journals (Sweden)

Paul P. Mebe

2008-12-01

Full Text Available Thermal stabilities of Pt(II complexes: K[PtCl3(CH2=CHSiMe3], K[PtCl3(CH2=CHCH2SiMe3], K[(acacPtCl(CH2=CHSiMe3] and [PtCl(CH2=CHCH2SiMe3]2, were examined. All complexes were found to be stable at room temperature but they decomposed without melting above about 90 oC. The allylsilane complex decomposed above about 125 oE,(E-1,4-diphenyl-1,3-butadiene was stereoselectively synthesised in good yield from (E-β-styrylsilane in the presence of Zeise’s salt.

Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation

DEFF Research Database (Denmark)

Helin, K; Wu, C L; Fattaey, A R

1993-01-01

the hypophosphorylated form of the retinoblastoma protein (pRB). The other protein, murine DP-1, was purified from an E2F DNA-affinity column, and it was subsequently shown to bind the consensus E2F DNA-binding site. To study a possible interaction between E2F-1 and DP-1, we have now isolated a cDNA for the human...

The deoxyhypusine synthase mutant dys1-1 reveals the association of eIF5A and Asc1 with cell wall integrity.

Directory of Open Access Journals (Sweden)

Fabio Carrilho Galvão

Full Text Available The putative eukaryotic translation initiation factor 5A (eIF5A is a highly conserved protein among archaea and eukaryotes that has recently been implicated in the elongation step of translation. eIF5A undergoes an essential and conserved posttranslational modification at a specific lysine to generate the residue hypusine. The enzymes deoxyhypusine synthase (Dys1 and deoxyhypusine hydroxylase (Lia1 catalyze this two-step modification process. Although several Saccharomyces cerevisiae eIF5A mutants have importantly contributed to the study of eIF5A function, no conditional mutant of Dys1 has been described so far. In this study, we generated and characterized the dys1-1 mutant, which showed a strong depletion of mutated Dys1 protein, resulting in more than 2-fold decrease in hypusine levels relative to the wild type. The dys1-1 mutant demonstrated a defect in total protein synthesis, a defect in polysome profile indicative of a translation elongation defect and a reduced association of eIF5A with polysomes. The growth phenotype of dys1-1 mutant is severe, growing only in the presence of 1 M sorbitol, an osmotic stabilizer. Although this phenotype is characteristic of Pkc1 cell wall integrity mutants, the sorbitol requirement from dys1-1 is not associated with cell lysis. We observed that the dys1-1 genetically interacts with the sole yeast protein kinase C (Pkc1 and Asc1, a component of the 40S ribosomal subunit. The dys1-1 mutant was synthetically lethal in combination with asc1Δ and overexpression of TIF51A (eIF5A or DYS1 is toxic for an asc1Δ strain. Moreover, eIF5A is more associated with translating ribosomes in the absence of Asc1 in the cell. Finally, analysis of the sensitivity to cell wall-perturbing compounds revealed a more similar behavior of the dys1-1 and asc1Δ mutants in comparison with the pkc1Δ mutant. These data suggest a correlated role for eIF5A and Asc1 in coordinating the translational control of a subset of m

The Japanese Mutant Aβ (ΔE22-Aβ1–39) Forms Fibrils Instantaneously, with Low-Thioflavin T Fluorescence: Seeding of Wild-Type Aβ1-40 into Atypical Fibrils by ΔE22-Aβ1-39

Science.gov (United States)

Cloe, Adam L.; Orgel, Joseph P.R.O.; Sachleben, Joseph R.; Tycko, Robert; Meredith, Stephen C.

2012-01-01

The ΔE693 (Japanese) mutation of the β-amyloid precursor protein leads to production of ΔE22-Aβ peptides such as ΔE22-Aβ1–39. Despite reports that these peptides do not form fibrils, here we show that, on the contrary, the peptide forms fibrils essentially instantaneously. The fibrils are typical amyloid fibrils in all respects except that they cause only low levels of thioflavin T (ThT) fluorescence, which, however, develops with no lag phase. The fibrils bind ThT, but with a lower affinity and a smaller number of binding sites than wild-type (WT) Aβ1–40. Fluorescence depolarization confirms extremely rapid aggregation of ΔE22-Aβ1–39. Size exclusion chromatography (SEC) indicates very low concentrations of soluble monomer and oligomer, but only in the presence of some organic solvent, e.g., 2% (v/v) DMSO. The critical concentration is approximately 1 order of magnitude lower for ΔE22-Aβ1–39 than for WTAβ1–40. Several lines of evidence point to an altered structure for ΔE22-Aβ1–39 compared to that of WT Aβ1–40 fibrils. In addition to differences in ThT binding and fluorescence, PITHIRDS-CT solid-state nuclear magnetic resonance (NMR) measurements of ΔE22-Aβ1–39 are not compatible with the parallel in-register β-sheet generally observed for WT Aβ1–40 fibrils. X-ray fibril diffraction showed different D spacings: 4.7 and 10.4 Å for WT Aβ1–40 and 4.7 and 9.6 Å for ΔE22-Aβ1–39. Equimolar mixtures of ΔE22-Aβ1–39 and WT Aβ1–40 also produced fibrils extremely rapidly, and by the criteria of ThT fluorescence and electron microscopic appearance, they were the same as fibrils made from pure ΔE22-Aβ1–39. X-ray diffraction of fibrils formed from 1:1 molar mixtures of ΔE22-Aβ1–39 and WT Aβ1–40 showed the same D spacings as fibrils of the pure mutant peptide, not the wild-type peptide. These findings are consistent with extremely rapid nucleation by ΔE22-Aβ1–39, followed by fibril extension by WT Aβ1–40, and

Total qualification of class 1E electric equipment

International Nuclear Information System (INIS)

Chauvin, G.

1982-09-01

For nuclear power plant projects in France, Framatome and its partners Electricite de France (EDF) and the Commissariat a l'Energie Atomique (CEA) have responded to the present qualification context by implementing a wide-ranging qualification program to acquire significant organizational and practical experience. The following sections detail Framatome's approach to the activities of an organization mandated to provide a complete spectrum of qualification services. Thorough implementation of a Class 1E electric equipment qualification program by the competent organization or qualifier entails completion of three consecutive steps: 1) program preparation, 2) program implementation, and 3) analysis of test results and conclusion. The qualifier assumes extensive responsibility for each of these steps. The following sections present test facilities used in France to conduct a total qualification program for Class 1E electric equipment

E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells.

Science.gov (United States)

Castillo, Daniela S; Campalans, Anna; Belluscio, Laura M; Carcagno, Abel L; Radicella, J Pablo; Cánepa, Eduardo T; Pregi, Nicolás

2015-01-01

E2F transcription factors regulate a wide range of biological processes, including the cellular response to DNA damage. In the present study, we examined whether E2F family members are transcriptionally induced following treatment with several genotoxic agents, and have a role on the cell DNA damage response. We show a novel mechanism, conserved among diverse species, in which E2F1 and E2F2, the latter specifically in neuronal cells, are transcriptionally induced after DNA damage. This upregulation leads to increased E2F1 and E2F2 protein levels as a consequence of de novo protein synthesis. Ectopic expression of these E2Fs in neuronal cells reduces the level of DNA damage following genotoxic treatment, while ablation of E2F1 and E2F2 leads to the accumulation of DNA lesions and increased apoptotic response. Cell viability and DNA repair capability in response to DNA damage induction are also reduced by the E2F1 and E2F2 deficiencies. Finally, E2F1 and E2F2 accumulate at sites of oxidative and UV-induced DNA damage, and interact with γH2AX DNA repair factor. As previously reported for E2F1, E2F2 promotes Rad51 foci formation, interacts with GCN5 acetyltransferase and induces histone acetylation following genotoxic insult. The results presented here unveil a new mechanism involving E2F1 and E2F2 in the maintenance of genomic stability in response to DNA damage in neuronal cells.

Autophagy Protects against CYP2E1/Chronic Ethanol-Induced Hepatotoxicity

Directory of Open Access Journals (Sweden)

Yongke Lu

2015-10-01

Full Text Available Autophagy is an intracellular pathway by which lysosomes degrade and recycle long-lived proteins and cellular organelles. The effects of ethanol on autophagy are complex but recent studies have shown that autophagy serves a protective function against ethanol-induced liver injury. Autophagy was found to also be protective against CYP2E1-dependent toxicity in vitro in HepG2 cells which express CYP2E1 and in vivo in an acute alcohol/CYPE1-dependent liver injury model. The goal of the current report was to extend the previous in vitro and acute in vivo experiments to a chronic ethanol model to evaluate whether autophagy is also protective against CYP2E1-dependent liver injury in a chronic ethanol-fed mouse model. Wild type (WT, CYP2E1 knockout (KO or CYP2E1 humanized transgenic knockin (KI, mice were fed an ethanol liquid diet or control dextrose diet for four weeks. In the last week, some mice received either saline or 3-methyladenine (3-MA, an inhibitor of autophagy, or rapamycin, which stimulates autophagy. Inhibition of autophagy by 3-MA potentiated the ethanol-induced increases in serum transaminase and triglyceride levels in the WT and KI mice but not KO mice, while rapamycin prevented the ethanol liver injury. Treatment with 3-MA enhanced the ethanol-induced fat accumulation in WT mice and caused necrosis in the KI mice; little or no effect was found in the ethanol-fed KO mice or any of the dextrose-fed mice. 3-MA treatment further lowered the ethanol-decrease in hepatic GSH levels and further increased formation of TBARS in WT and KI mice, whereas rapamycin blunted these effects of ethanol. Neither 3-MA nor rapamycin treatment affected CYP2E1 catalytic activity or content or the induction CYP2E1 by ethanol. The 3-MA treatment decreased levels of Beclin-1 and Atg 7 but increased levels of p62 in the ethanol-fed WT and KI mice whereas rapamycin had the opposite effects, validating inhibition and stimulation of autophagy, respectively. These

Structure, dynamics, and interaction of Mycobacterium tuberculosis (Mtb DprE1 and DprE2 examined by molecular modeling, simulation, and electrostatic studies.

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Isha Bhutani

Full Text Available The enzymes decaprenylphosphoryl-β-D-ribose oxidase (DprE1 and decaprenylphosphoryl-β-D-ribose-2-epimerase (DprE2 catalyze epimerization of decaprenylphosporyl ribose (DPR todecaprenylphosporyl arabinose (DPA and are critical for the survival of Mtb. Crystal structures of DprE1 so far reported display significant disordered regions and no structural information is known for DprE2. We used homology modeling, protein threading, molecular docking and dynamics studies to investigate the structural and dynamic features of Mtb DprE1 and DprE2 and DprE1-DprE2 complex. A three-dimensional model for DprE2 was generated using the threading approach coupled with ab initio modeling. A 50 ns simulation of DprE1 and DprE2 revealed the overall stability of the structures. Principal Component Analysis (PCA demonstrated the convergence of sampling in both DprE1 and DprE2. In DprE1, residues in the 269-330 area showed considerable fluctuation in agreement with the regions of disorder observed in the reported crystal structures. In DprE2, large fluctuations were detected in residues 95-113, 146-157, and 197-226. The study combined docking and MD simulation studies to map and characterize the key residues involved in DprE1-DprE2 interaction. A 60 ns MD simulation for DprE1-DprE2 complex was also performed. Analysis of data revealed that the docked complex is stabilized by H-bonding, hydrophobic and ionic interactions. The key residues of DprE1 involved in DprE1-DprE2 interactions belong to the disordered region. We also examined the docked complex of DprE1-BTZ043 to investigate the binding pocket of DprE1 and its interactions with the inhibitor BTZ043. In summary, we hypothesize that DprE1-DprE2 interaction is crucial for the synthesis of DPA and DprE1-DprE2 complex may be a new therapeutic target amenable to pharmacological validation. The findings have important implications in tuberculosis (TB drug discovery and will facilitate drug development efforts against

26 CFR 31.3402(e)-1 - Included and excluded wages.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Included and excluded wages. 31.3402(e)-1... SOURCE Collection of Income Tax at Source § 31.3402(e)-1 Included and excluded wages. (a) If a portion of... not more than 31 consecutive days constitutes wages, and the remainder does not constitute wages, all...

Photon radiation in e+e-→hadrons at low energies with carlomat3.1

International Nuclear Information System (INIS)

Jegerlehner, Fred; Humboldt-Universitaet, Berlin; Kolodziej, Karol

2017-01-01

We present a sample of results for the cross sections of several processes of low energetic e + e - annihilation into final states containing pions accompanied by one or two photons, or a light lepton pair. The results, which have been obtained with a new version of a multipurpose Monte Carlo program carlomat, labelled 3.1, demonstrate new capabilities of the program which, among others, include a possibility of taking into account either the initial or final state radiation separately, or both at a time, and a possibility of inclusion of the electromagnetic charged pion form factor for processes with charged pion pairs. We also discuss some problems related to the U(1) electromagnetic gauge invariance.

In vitro characterization of the NAD+ synthetase NadE1 from Herbaspirillum seropedicae.

Science.gov (United States)

Laskoski, Kerly; Santos, Adrian R S; Bonatto, Ana C; Pedrosa, Fábio O; Souza, Emanuel M; Huergo, Luciano F

2016-05-01

Nicotinamide adenine dinucleotide synthetase enzyme (NadE) catalyzes the amination of nicotinic acid adenine dinucleotide (NaAD) to form NAD(+). This reaction represents the last step in the majority of the NAD(+) biosynthetic routes described to date. NadE enzymes typically use either glutamine or ammonium as amine nitrogen donor, and the reaction is energetically driven by ATP hydrolysis. Given the key role of NAD(+) in bacterial metabolism, NadE has attracted considerable interest as a potential target for the development of novel antibiotics. The plant-associative nitrogen-fixing bacteria Herbaspirillum seropedicae encodes two putative NadE, namely nadE1 and nadE2. The nadE1 gene is linked to glnB encoding the signal transduction protein GlnB. Here we report the purification and in vitro characterization of H. seropedicae NadE1. Gel filtration chromatography analysis suggests that NadE1 is an octamer. The NadE1 activity was assayed in vitro, and the Michaelis-Menten constants for substrates NaAD, ATP, glutamine and ammonium were determined. Enzyme kinetic and in vitro substrate competition assays indicate that H. seropedicae NadE1 uses glutamine as a preferential nitrogen donor.

Proteomic analysis of trichloroethylene-induced alterations in expression, distribution, and interactions of SET/TAF-Iα and two SET/TAF-Iα-binding proteins, eEF1A1 and eEF1A2, in hepatic L-02 cells

Energy Technology Data Exchange (ETDEWEB)

Hong, Wen-Xu; Yang, Liang; Chen, Moutong; Yang, Xifei; Ren, Xiaohu; Fang, Shisong; Ye, Jinbo; Huang, Haiyan; Peng, Chaoqiong; Zhou, Li; Huang, Xinfeng; Yang, Fan; Wu, Desheng; Zhuang, Zhixiong; Liu, Jianjun, E-mail: bio-research@hotmail.com

2012-09-01

Emerging evidence indicates that trichloroethylene (TCE) exposure causes severe hepatotoxicity. However, the mechanisms of TCE hepatotoxicity remain unclear. Recently, we reported that TCE exposure up-regulated the expression of the oncoprotein SET/TAF-Iα and SET knockdown attenuated TCE-induced cytotoxicity in hepatic L-02 cells. To decipher the function of SET/TAF-Iα and its contributions to TCE-induced hepatotoxicity, we employed a proteomic analysis of SET/TAF-Iα with tandem affinity purification to identify SET/TAF-Iα-binding proteins. We identified 42 novel Gene Ontology co-annotated SET/TAF-Iα-binding proteins. The identifications of two of these proteins (eEF1A1, elongation factor 1-alpha 1; eEF1A2, elongation factor 1-alpha 2) were confirmed by Western blot analysis and co-immunoprecipitation (Co-IP). Furthermore, we analyzed the effects of TCE on the expression, distribution and interactions of eEF1A1, eEF1A2 and SET in L-02 cells. Western blot analysis reveals a significant up-regulation of eEF1A1, eEF1A2 and two isoforms of SET, and immunocytochemical analysis reveals that eEF1A1 and SET is redistributed by TCE. SET is redistributed from the nucleus to the cytoplasm, while eFE1A1 is translocated from the cytoplasm to the nucleus. Moreover, we find by Co-IP that TCE exposure significantly increases the interaction of SET with eEF1A2. Our data not only provide insights into the physiological functions of SET/TAF-Iα and complement the SET interaction networks, but also demonstrate that TCE exposure induces alterations in the expression, distribution and interactions of SET and its binding partners. These alterations may constitute the mechanisms of TCE cytotoxicity. -- Highlights: ► Identify 62 SET/TAF-Iα-associated proteins in human L-02 cells ► Trichloroethylene (TCE) alters the interaction of SET with eEF1A1 and eEF1A2. ► TCE induces the translocation and up-regulation of SET. ► TCE induces the translocation and up-regulation of eEF1A.

Proteomic analysis of trichloroethylene-induced alterations in expression, distribution, and interactions of SET/TAF-Iα and two SET/TAF-Iα-binding proteins, eEF1A1 and eEF1A2, in hepatic L-02 cells

International Nuclear Information System (INIS)

Hong, Wen-Xu; Yang, Liang; Chen, Moutong; Yang, Xifei; Ren, Xiaohu; Fang, Shisong; Ye, Jinbo; Huang, Haiyan; Peng, Chaoqiong; Zhou, Li; Huang, Xinfeng; Yang, Fan; Wu, Desheng; Zhuang, Zhixiong; Liu, Jianjun

2012-01-01

Emerging evidence indicates that trichloroethylene (TCE) exposure causes severe hepatotoxicity. However, the mechanisms of TCE hepatotoxicity remain unclear. Recently, we reported that TCE exposure up-regulated the expression of the oncoprotein SET/TAF-Iα and SET knockdown attenuated TCE-induced cytotoxicity in hepatic L-02 cells. To decipher the function of SET/TAF-Iα and its contributions to TCE-induced hepatotoxicity, we employed a proteomic analysis of SET/TAF-Iα with tandem affinity purification to identify SET/TAF-Iα-binding proteins. We identified 42 novel Gene Ontology co-annotated SET/TAF-Iα-binding proteins. The identifications of two of these proteins (eEF1A1, elongation factor 1-alpha 1; eEF1A2, elongation factor 1-alpha 2) were confirmed by Western blot analysis and co-immunoprecipitation (Co-IP). Furthermore, we analyzed the effects of TCE on the expression, distribution and interactions of eEF1A1, eEF1A2 and SET in L-02 cells. Western blot analysis reveals a significant up-regulation of eEF1A1, eEF1A2 and two isoforms of SET, and immunocytochemical analysis reveals that eEF1A1 and SET is redistributed by TCE. SET is redistributed from the nucleus to the cytoplasm, while eFE1A1 is translocated from the cytoplasm to the nucleus. Moreover, we find by Co-IP that TCE exposure significantly increases the interaction of SET with eEF1A2. Our data not only provide insights into the physiological functions of SET/TAF-Iα and complement the SET interaction networks, but also demonstrate that TCE exposure induces alterations in the expression, distribution and interactions of SET and its binding partners. These alterations may constitute the mechanisms of TCE cytotoxicity. -- Highlights: ► Identify 62 SET/TAF-Iα-associated proteins in human L-02 cells ► Trichloroethylene (TCE) alters the interaction of SET with eEF1A1 and eEF1A2. ► TCE induces the translocation and up-regulation of SET. ► TCE induces the translocation and up-regulation of eEF1A.

Production of recombinant proteins GST L1, E6 and E7 tag HPV 16 ...

African Journals Online (AJOL)

In the present work recombinant proteins were produced for used in LUMINEX in order to undergo serological study of Tunisian female population. HPV types 16 L1, E6 and E7 sequences fused to their 3'-end to a sequence encoding the terminal undecapeptide of the SV40 large T-antigen (tag) were isolated from plasmids ...

Main: 1.00E+55 [RPSD[Archive

Lifescience Database Archive (English)

Full Text Available Zea Mays Molecule: Beta-Glucosidase; Chain: A, B; Engineered: Yes Glycoside Hydrolase 3.2.1.21 (Beta-Glucos...lucosidases Is Revealed By Crystal Structures Of Mutant Maize Beta -Glucosidase- Dimboa, -Dimboaglc, And -Dh...ntion Of The Anomeric Configuration, Inactive Mutant E191d, Complex With Dhurrin SWS:BGLC_MAI...; A/B=55-566.|PDB; 1HXJ; X-ray; A/B=60-566.|Maize-2DPAGE; P49235; COLEOPTILE.|MaizeDB; 13870; -.|InterPro; I

O vírus Influenza H1N1 e os trabalhadores da suinocultura: uma revisão

Directory of Open Access Journals (Sweden)

Neidimila Aparecida Silveira Oliveira

Full Text Available Considerando-se o grande impacto midiático e populacional da recente epidemia pelo vírus Influenza H1N1, em função do seu risco potencial de alta letalidade, decidimos realizar esta revisão, de forma a melhor compreender as relações entre a exposição aos suínos e a possível contaminação laboral. A influenza, também conhecida como gripe, é uma doença viral adquirida através do contato humano com animais domesticados. Os suínos são importantes hospedeiros do vírus Influenza H1N1 (swine-like Influenza A e susceptíveis às infecções por vírus Influenza de origem aviária e humana. Os suínos possuem importante papel na transmissão viral entre espécies e na epidemiologia da influenza humana. A epidemia por Influenza A H1N1/2009 representou um grande desafio para as autoridades públicas e setores privados da saúde, no que se refere às medidas de planejamento e execução de ações de prevenção e tratamento. Estima-se que 89 milhões de pessoas tenham sido contaminadas por este vírus, com até 403 mil casos de hospitalização e 18.300 óbitos até abril de 2010. Embora estejamos em período pós-pandemia, acredita-se que o vírus H1N1 tenha atualmente um comportamento semelhante ao vírus de gripe sazonal, causando focos infecciosos localizados e com níveis ainda significativos de transmissão. Destaca-se a preocupação com a saúde dos trabalhadores diretamente ligados à suinocultura, já que essa atividade produtiva apresenta uma situação de risco aos trabalhadores envolvidos e também à comunidade.

E-VPMS 1.0: Enhanced Vehicle Parking Monitoring System

Directory of Open Access Journals (Sweden)

Shian Lim Yeu

2018-01-01

Full Text Available Due to lack of vehicle parking slot in front of Block Q, Faculty of Electrical and Electronic Engineering (FKEE, UTHM, the enhanced vehicle parking monitoring system (E-VPMS 1.0 is developed to identify parking slots available in the parking area as well as to detect double parking problem. Once this system is implemented, time consume for searching available parking slots as well as double parking problem that may cause unwanted accident can be reduced. In the development of E-VPMS 1.0 system, whole system are designed and developed in three different phases; which are video processing phase, login and registration phase, and webview development phase. In video processing phase, video sources are processed through few video processing function. In login and registration phase, series of webpage function have been created that accessible in both smartphone and laptop. While, in webview development phase, webview function have been developed and through this function, content of E-VPMS 1.0 system can be displayed directly via web browser for both smartphone and laptop. Through E-VPMS 1.0, availability parking slots can be checked by registered user through input recorded video before entering the specific parking area. Other than that, performance analysis in terms of numbers of registered user and parking slot availability at different situations such as during peak event or normal event can be managed and controlled by admin through visualisation data method.

Vitamin E δ-tocotrienol induces p27(Kip1-dependent cell-cycle arrest in pancreatic cancer cells via an E2F-1-dependent mechanism.

Directory of Open Access Journals (Sweden)

Pamela J Hodul

Full Text Available Vitamin E δ-tocotrienol has been shown to have antitumor activity, but the precise molecular mechanism by which it inhibits the proliferation of cancer cells remains unclear. Here, we demonstrated that δ-tocotrienol exerted significant cell growth inhibition pancreatic ductal cancer (PDCA cells without affecting normal human pancreatic ductal epithelial cell growth. We also showed that δ-tocotrienol-induced growth inhibition occurred concomitantly with G(1 cell-cycle arrest and increased p27(Kip1 nuclear accumulation. This finding is significant considering that loss of nuclear p27(Kip1 expression is a well-established adverse prognostic factor in PDCA. Furthermore, δ-tocotrienol inactivated RAF-MEK-ERK signaling, a pathway known to suppress p27(Kip1 expression. To determine whether p27(Kip1 induction is required for δ-tocotrienol inhibition of PDCA cell proliferation, we stably silenced the CDKN1B gene, encoding p27(Kip1, in MIAPaCa-2 PDCA cells and demonstrated that p27(Kip1 silencing suppressed cell-cycle arrest induced by δ-tocotrienol. Furthermore, δ-tocotrienol induced p27(Kip1 mRNA expression but not its protein degradation. p27(Kip1 gene promoter activity was induced by δ-tocotrienol through the promoter's E2F-1 binding site, and this activity was attenuated by E2F-1 depletion using E2F-1 small interfering RNA. Finally, decreased proliferation, mediated by Ki67 and p27(Kip1 expression by δ-tocotrienol, was confirmed in vivo in a nude mouse xenograft pancreatic cancer model. Our findings reveal a new mechanism, dependent on p27(Kip1 induction, by which δ-tocotrienol can inhibit proliferation in PDCA cells, providing a new rationale for p27(Kip1 as a biomarker for δ-tocotrienol efficacy in pancreatic cancer prevention and therapy.

Observation of e+e-→ϕ χc 1 and ϕ χc 2 at √{s }=4.600 GeV

Science.gov (United States)

Ablikim, M.; Achasov, M. N.; Ahmed, S.; Albrecht, M.; Amoroso, A.; An, F. F.; An, Q.; Bai, J. Z.; Bai, Y.; Bakina, O.; Baldini Ferroli, R.; Ban, Y.; Bennett, D. W.; Bennett, J. V.; Berger, N.; Bertani, M.; Bettoni, D.; Bian, J. M.; Bianchi, F.; Boger, E.; Boyko, I.; Briere, R. A.; Cai, H.; Cai, X.; Cakir, O.; Calcaterra, A.; Cao, G. F.; Cetin, S. A.; Chai, J.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, J. C.; Chen, M. L.; Chen, P. L.; Chen, S. J.; Chen, X. R.; Chen, Y. B.; Chu, X. K.; Cibinetto, G.; Dai, H. L.; Dai, J. P.; Dbeyssi, A.; Dedovich, D.; Deng, Z. Y.; Denig, A.; Denysenko, I.; Destefanis, M.; de Mori, F.; Ding, Y.; Dong, C.; Dong, J.; Dong, L. Y.; Dong, M. Y.; Dou, Z. L.; Du, S. X.; Duan, P. F.; Fang, J.; Fang, S. S.; Fang, Y.; Farinelli, R.; Fava, L.; Fegan, S.; Feldbauer, F.; Felici, G.; Feng, C. Q.; Fioravanti, E.; Fritsch, M.; Fu, C. D.; Gao, Q.; Gao, X. L.; Gao, Y.; Gao, Y. G.; Gao, Z.; Garzia, I.; Goetzen, K.; Gong, L.; Gong, W. X.; Gradl, W.; Greco, M.; Gu, M. H.; Gu, Y. T.; Guo, A. Q.; Guo, R. P.; Guo, Y. P.; Haddadi, Z.; Han, S.; Hao, X. Q.; Harris, F. A.; He, K. L.; He, X. Q.; Heinsius, F. H.; Held, T.; Heng, Y. K.; Holtmann, T.; Hou, Z. L.; Hu, H. M.; Hu, T.; Hu, Y.; Huang, G. S.; Huang, J. S.; Huang, X. T.; Huang, X. Z.; Huang, Z. L.; Hussain, T.; Ikegami Andersson, W.; Ji, Q.; Ji, Q. P.; Ji, X. B.; Ji, X. L.; Jiang, X. S.; Jiang, X. Y.; Jiao, J. B.; Jiao, Z.; Jin, D. P.; Jin, S.; Jin, Y.; Johansson, T.; Julin, A.; Kalantar-Nayestanaki, N.; Kang, X. L.; Kang, X. S.; Kavatsyuk, M.; Ke, B. C.; Khan, T.; Khoukaz, A.; Kiese, P.; Kliemt, R.; Koch, L.; Kolcu, O. B.; Kopf, B.; Kornicer, M.; Kuemmel, M.; Kuessner, M.; Kuhlmann, M.; Kupsc, A.; Kühn, W.; Lange, J. S.; Lara, M.; Larin, P.; Lavezzi, L.; Leithoff, H.; Leng, C.; Li, C.; Li, Cheng; Li, D. M.; Li, F.; Li, F. Y.; Li, G.; Li, H. B.; Li, H. J.; Li, J. C.; Li, Jin; Li, K. J.; Li, Kang; Li, Ke; Li, Lei; Li, P. L.; Li, P. R.; Li, Q. Y.; Li, W. D.; Li, W. G.; Li, X. L.; Li, X. N.; Li, X. Q.; Li, Z. B.; Liang, H.; Liang, Y. F.; Liang, Y. T.; Liao, G. R.; Lin, D. X.; Liu, B.; Liu, B. J.; Liu, C. X.; Liu, D.; Liu, F. H.; Liu, Fang; Liu, Feng; Liu, H. B.; Liu, H. M.; Liu, Huanhuan; Liu, Huihui; Liu, J. B.; Liu, J. P.; Liu, J. Y.; Liu, K.; Liu, K. Y.; Liu, Ke; Liu, L. D.; Liu, P. L.; Liu, Q.; Liu, S. B.; Liu, X.; Liu, Y. B.; Liu, Z. A.; Liu, Zhiqing; Long, Y. F.; Lou, X. C.; Lu, H. J.; Lu, J. G.; Lu, Y.; Lu, Y. P.; Luo, C. L.; Luo, M. X.; Luo, X. L.; Lyu, X. R.; Ma, F. C.; Ma, H. L.; Ma, L. L.; Ma, M. M.; Ma, Q. M.; Ma, T.; Ma, X. N.; Ma, X. Y.; Ma, Y. M.; Maas, F. E.; Maggiora, M.; Malik, Q. A.; Mao, Y. J.; Mao, Z. P.; Marcello, S.; Meng, Z. X.; Messchendorp, J. G.; Mezzadri, G.; Min, J.; Min, T. J.; Mitchell, R. E.; Mo, X. H.; Mo, Y. J.; Morales Morales, C.; Muchnoi, N. Yu.; Muramatsu, H.; Musiol, P.; Mustafa, A.; Nefedov, Y.; Nerling, F.; Nikolaev, I. B.; Ning, Z.; Nisar, S.; Niu, S. L.; Niu, X. Y.; Olsen, S. L.; Ouyang, Q.; Pacetti, S.; Pan, Y.; Papenbrock, M.; Patteri, P.; Pelizaeus, M.; Pellegrino, J.; Peng, H. P.; Peters, K.; Pettersson, J.; Ping, J. L.; Ping, R. G.; Pitka, A.; Poling, R.; Prasad, V.; Qi, H. R.; Qi, M.; Qian, S.; Qiao, C. F.; Qin, N.; Qin, X. S.; Qin, Z. H.; Qiu, J. F.; Rashid, K. H.; Redmer, C. F.; Richter, M.; Ripka, M.; Rolo, M.; Rong, G.; Rosner, Ch.; Sarantsev, A.; Savrié, M.; Schnier, C.; Schoenning, K.; Shan, W.; Shao, M.; Shen, C. P.; Shen, P. X.; Shen, X. Y.; Sheng, H. Y.; Song, J. J.; Song, W. M.; Song, X. Y.; Sosio, S.; Sowa, C.; Spataro, S.; Sun, G. X.; Sun, J. F.; Sun, L.; Sun, S. S.; Sun, X. H.; Sun, Y. J.; Sun, Y. K.; Sun, Y. Z.; Sun, Z. J.; Sun, Z. T.; Tang, C. J.; Tang, G. Y.; Tang, X.; Tapan, I.; Tiemens, M.; Tsednee, B.; Uman, I.; Varner, G. S.; Wang, B.; Wang, B. L.; Wang, D.; Wang, D. Y.; Wang, Dan; Wang, K.; Wang, L. L.; Wang, L. S.; Wang, M.; Wang, Meng; Wang, P.; Wang, P. L.; Wang, W. P.; Wang, X. F.; Wang, Y.; Wang, Y. D.; Wang, Y. F.; Wang, Y. Q.; Wang, Z.; Wang, Z. G.; Wang, Z. Y.; Wang, Zongyuan; Weber, T.; Wei, D. H.; Weidenkaff, P.; Wen, S. P.; Wiedner, U.; Wolke, M.; Wu, L. H.; Wu, L. J.; Wu, Z.; Xia, L.; Xia, Y.; Xiao, D.; Xiao, H.; Xiao, Y. J.; Xiao, Z. J.; Xie, Y. G.; Xie, Y. H.; Xiong, X. A.; Xiu, Q. L.; Xu, G. F.; Xu, J. J.; Xu, L.; Xu, Q. J.; Xu, Q. N.; Xu, X. P.; Yan, L.; Yan, W. B.; Yan, W. C.; Yan, Y. H.; Yang, H. J.; Yang, H. X.; Yang, L.; Yang, Y. H.; Yang, Y. X.; Ye, M.; Ye, M. H.; Yin, J. H.; You, Z. Y.; Yu, B. X.; Yu, C. X.; Yu, J. S.; Yuan, C. Z.; Yuan, Y.; Yuncu, A.; Zafar, A. A.; Zeng, Y.; Zeng, Z.; Zhang, B. X.; Zhang, B. Y.; Zhang, C. C.; Zhang, D. H.; Zhang, H. H.; Zhang, H. Y.; Zhang, J.; Zhang, J. L.; Zhang, J. Q.; Zhang, J. W.; Zhang, J. Y.; Zhang, J. Z.; Zhang, K.; Zhang, L.; Zhang, S. Q.; Zhang, X. Y.; Zhang, Y. H.; Zhang, Y. T.; Zhang, Yang; Zhang, Yao; Zhang, Yu; Zhang, Z. H.; Zhang, Z. P.; Zhang, Z. Y.; Zhao, G.; Zhao, J. W.; Zhao, J. Y.; Zhao, J. Z.; Zhao, Lei; Zhao, Ling; Zhao, M. G.; Zhao, Q.; Zhao, S. J.; Zhao, T. C.; Zhao, Y. B.; Zhao, Z. G.; Zhemchugov, A.; Zheng, B.; Zheng, J. P.; Zheng, W. J.; Zheng, Y. H.; Zhong, B.; Zhou, L.; Zhou, X.; Zhou, X. K.; Zhou, X. R.; Zhou, X. Y.; Zhou, Y. X.; Zhu, J.; Zhu, J.; Zhu, K.; Zhu, K. J.; Zhu, S.; Zhu, S. H.; Zhu, X. L.; Zhu, Y. C.; Zhu, Y. S.; Zhu, Z. A.; Zhuang, J.; Zou, B. S.; Zou, J. H.; Besiii Collaboration

2018-02-01

Using a data sample collected with the BESIII detector operating at the BEPCII storage ring at a center-of-mass energy of √{s }=4.600 GeV , we search for the production of e+e-→ϕ χc 0 ,1 ,2 . A search is also performed for the charmonium-like state X (4140 ) in the radiative transition e+e-→γ X (4140 ) with X (4140 ) subsequently decaying into ϕ J /ψ . The processes e+e-→ϕ χc 1 and ϕ χc 2 are observed for the first time, each with a statistical significance of more than 10 σ , and the Born cross sections are measured to be (4. 2-1.0+1.7±0.3 ) and (6. 7-1.7+3.4±0.5 ) pb , respectively, where the first uncertainties are statistical and the second systematic. No significant signals are observed for e+e-→ϕ χc 0 and e+e-→γ X (4140 ) and upper limits on the Born cross sections at 90% C.L. are provided at √{s }=4.600 GeV .

Editorial L&E, v.7, n.1, 2013.

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Rede Conpadre

2013-02-01

Full Text Available Editorial L&E, v.7, n.1, 2013 L’architettura, in quanto bene d’uso, è da considerarsi come un’opera aperta, destinata a venire, nel corso della sua esistenza, modificata, trasformata, integrata per poter continuare ad essere utilizzata e fruita. Le architetture che sono state oggetto di dismissione, a seguito del venir meno delle motivazioni (funzioni per le quali esse erano state realizzate, sono, più di altre, destinate a subire tali trasformazioni. Sono, infatti, architetture ormai deboli e fragili, nella maggior parte dei casi considerate prive di valore o quasi, che proprio in virtù di queste considerazioni vengono abbandonate e/o distrutte, decretandone irrimediabilmente la scomparsa. Il patrimonio industriale dismesso rientra a pieno titolo in tale categoria di manufatti architettonici e, purtroppo, nel corso del tempo, è stato sottoposto a qualsivoglia tipo di manomissione, ivi compresa la demolizione. Si tratta però di un patrimonio che, a ben guardare, risulta ancora ricco di qualità e di potenzialità che potrebbe/dovrebbe essere adeguatamente valorizzato attraverso lo studio e la messa a punto di soluzioni che consentano di massimizzare la permanenza, pur prestando attenzione al problema della sostenibilità degli interventi sia in fase di realizzazione degli stessi, sia in fase di utilizzo dei beni sottoposti ai necessari e appropriati interventi di rifunzionalizzazione. Solo in questo modo tale patrimonio può cessare di rappresentare un “problema” per i proprietari, pubblici o privati che siano, per divenire una risorsa – architettonica, culturale e, perché no, anche materiale – garantendone la permanenza nel tempo – magari trasformata, sicuramente arricchita da nuove tracce – e la trasmissione alle future generazioni. Manuela Mattone

Editorial L&E, v.8, n.1, 2014

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Rede Conpadre

2014-02-01

Full Text Available A Revista Labor & Engenho chega ao seu oitavo ano (quinto com periodicidade trimestral apresentando aos leitores uma atualização do seu layout — que permanece o mesmo, porém com o design levemente modificado a fim de otimizar o corpo do texto e ressaltar no cabeçalho o nome por extenso e a sigla [L&E] da Revista. Também o design das bandeiras correspondentes às diferentes nacionalidades representadas por cada autor da Revista receberam um toque especial a fim de promover um certo destaque. As modificações, embora sutis, contribuem para a consolidação do caráter internacional da Revista Labor & Engenho [ISSN: 2176-8846]. O número 1 do volume 8 (2014 traz 7 artigos: 4 de autores brasileiros (dentre os quais, 3 em português, 1 em inglês; 2 de autores argentinos (em espanhol; e 1 de autor mexicano (em espanhol. Dentre os artigos brasileiros encontram-se representantes de instituições dos estados de São Paulo, Minas Gerais, Espírito Santo, e Rio Grande do Sul. Os artigos argentinos, assim como o artigo mexicano, apresentam aspectos regionais distintos que contribuem para a consolidação da Revista L&E como uma publicação relevante para quem quer que se interesse pelos temas de Trabalho [Labor] & Genialidade [Engenho], Patrimônio & Desenvolvimento Regional, ou Paisagem & Engenharia, ou ainda, Ordenamento Territorial & Sustentabilidade. O primeiro artigo deste número trata das relações existentes entre os meios urbano e rural, a partir de uma análise sobre os padrões de consumo, comportamento e tipo de ocupação no interior de Minas Gerais. O estudo realizado permitiu inferir sobre a necessidade de se incrementar pesquisas sobre o meio rural e as pequenas cidades no Brasil, a fim de conhecer melhor esses espaços e o sistema urbano brasileiro (SOARES; SIOLARI; DIAS, 2014. E já que estamos focados na paisagem rural de Minas Gerais, então a leitura do próximo artigo mostra-se pertinente e instigante. Apresenta-se uma

Functional immunoglobulin E cross-reactivity between Pas n 1 of Bahia grass pollen and other group 1 grass pollen allergens.

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Davies, J M; Dang, T D; Voskamp, A; Drew, A C; Biondo, M; Phung, M; Upham, J W; Rolland, J M; O'Hehir, R E

2011-02-01

Grass pollens are major triggers of allergic rhinitis and asthma, but the immunological relationships between pollen allergens of the subtropical Bahia grass, Paspalum notatum, and temperate grasses are unresolved. To assess serum IgE cross-reactivity between subtropical P. notatum and temperate Lolium perenne (Ryegrass) pollen allergens. Serum IgE reactivities of grass pollen-allergic patients with P. notatum, L. perenne and Cynodon dactylon (Bermuda grass) pollen extracts and their respective purified group 1 allergens, Pas n 1, Lol p 1 and Cyn d 1, were compared by immunoblotting, ELISA and basophil activation. In a cohort of 51 patients from a temperate region, a high frequency of IgE reactivity with each grass pollen was detected, but reactivity with L. perenne pollen was substantially greater than with P. notatum and C. dactylon pollen. Similarly, serum IgE reactivity with Lol p 1 was greater than with Pas n 1 or Cyn d 1. For seven of eight sera studied in detail, asymmetric serum IgE cross-reactivity was observed; L. perenne pollen inhibited IgE reactivity with P. notatum pollen but not the converse, and IgE reactivity with Pas n 1 was inhibited by Lol p 1 but IgE reactivity with Lol p 1 was not inhibited by Pas n 1 or Cyn d 1. Importantly, P. notatum pollen and Pas n 1 activated basophils in grass pollen-allergic patients from a temperate region, although stimulation was greater by pollen of L. perenne than P. notatum or C. dactylon, and by Lol p 1 than Pas n 1 or Cyn d 1. In contrast, a cohort of 47 patients from a subtropical region showed similar IgE reactivity with P. notatum and L. perenne pollen, and reciprocal cross-inhibition of IgE reactivity between L. perenne and P. notatum. Pollen allergens of the subtropical P. notatum, including Pas n 1, show clinically relevant IgE cross-reactivity with pollen allergens of L. perenne but also species-specific IgE reactivity. © 2011 Blackwell Publishing Ltd.

17 CFR 240.14e-1 - Unlawful tender offer practices.

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2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Unlawful tender offer... Securities Exchange Act of 1934 Regulation 14e § 240.14e-1 Unlawful tender offer practices. As a means... section 14(e) of the Act, no person who makes a tender offer shall: (a) Hold such tender offer open for...

e-Cadherin in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinson Disease

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Samuela Cataldi

2016-01-01

Full Text Available Today a large number of studies are focused on clarifying the complexity and diversity of the pathogenetic mechanisms inducing Parkinson disease. We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, a neurotoxin that induces Parkinson disease, to evaluate the change of midbrain structure and the behavior of the anti-inflammatory factor e-cadherin, interleukin-6, tyrosine hydroxylase, phosphatase and tensin homolog, and caveolin-1. The results showed a strong expression of e-cadherin, variation of length and thickness of the heavy neurofilaments, increase of interleukin-6, and reduction of tyrosine hydroxylase known to be expression of dopamine cell loss, reduction of phosphatase and tensin homolog described to impair responses to dopamine, and reduction of caveolin-1 known to be expression of epithelial-mesenchymal transition and fibrosis. The possibility that the overexpression of the e-cadherin might be implicated in the anti-inflammatory reaction to MPTP treatment by influencing the behavior of the other analyzed molecules is discussed.

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

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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.

Protein tyrosine phosphatase 1B (PTP1B) is dispensable for IgE-mediated cutaneous reaction in vivo.

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Yang, Ting; Xie, Zhongping; Li, Hua; Yue, Lei; Pang, Zheng; MacNeil, Adam J; Tremblay, Michel L; Tang, Jin-Tian; Lin, Tong-Jun

2016-01-01

Mast cells play a critical role in allergic reactions. The cross-linking of FcεRI-bound IgE with multivalent antigen initiates a cascade of signaling events leading to mast cell activation. It has been well-recognized that cross linking of FcεRI mediates tyrosine phosphorylation. However, the mechanism involved in tyrosine dephosphorylation in mast cells is less clear. Here we demonstrated that protein tyrosine phosphatase 1B (PTP1B)-deficient mast cells showed increased IgE-mediated phosphorylation of the signal transducer and activator of transcription 5 (STAT5) and enhanced production of CCL9 (MIP-1γ) and IL-6 in IgE-mediated mast cells activation in vitro. However, IgE-mediated calcium mobilization, β-hexaosaminidase release (degranulation), and phosphorylation of IκB and MAP kinases were not affected by PTP1B deficiency. Furthermore, PTP1B deficient mice showed normal IgE-dependent passive cutaneous anaphylaxis and late phase cutaneous reactions in vivo. Thus, PTP1B specifically regulates IgE-mediated STAT5 pathway, but is redundant in influencing mast cell function in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

PED/PEA-15 inhibits hydrogen peroxide-induced apoptosis in Ins-1E pancreatic beta-cells via PLD-1.

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Francesca Fiory

Full Text Available The small scaffold protein PED/PEA-15 is involved in several different physiologic and pathologic processes, such as cell proliferation and survival, diabetes and cancer. PED/PEA-15 exerts an anti-apoptotic function due to its ability to interfere with both extrinsic and intrinsic apoptotic pathways in different cell types. Recent evidence shows that mice overexpressing PED/PEA-15 present larger pancreatic islets and increased beta-cells mass. In the present work we investigated PED/PEA-15 role in hydrogen peroxide-induced apoptosis in Ins-1E beta-cells. In pancreatic islets isolated from Tg(PED/PEA-15 mice hydrogen peroxide-induced DNA fragmentation was lower compared to WT islets. TUNEL analysis showed that PED/PEA-15 overexpression increases the viability of Ins-1E beta-cells and enhances their resistance to apoptosis induced by hydrogen peroxide exposure. The activity of caspase-3 and the cleavage of PARP-1 were markedly reduced in Ins-1E cells overexpressing PED/PEA-15 (Ins-1E(PED/PEA-15. In parallel, we observed a decrease of the mRNA levels of pro-apoptotic genes Bcl-xS and Bad. In contrast, the expression of the anti-apoptotic gene Bcl-xL was enhanced. Accordingly, DNA fragmentation was higher in control cells compared to Ins-1E(PED/PEA-15 cells. Interestingly, the preincubation with propranolol, an inhibitor of the pathway of PLD-1, a known interactor of PED/PEA-15, responsible for its deleterious effects on glucose tolerance, abolishes the antiapoptotic effects of PED/PEA-15 overexpression in Ins-1E beta-cells. The same results have been obtained by inhibiting PED/PEA-15 interaction with PLD-1 in Ins-1E(PED/PEA-15. These results show that PED/PEA-15 overexpression is sufficient to block hydrogen peroxide-induced apoptosis in Ins-1E cells through a PLD-1 mediated mechanism.

Aberrant signature methylome by DNMT1 hot spot mutation in hereditary sensory and autonomic neuropathy 1E.

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Sun, Zhifu; Wu, Yanhong; Ordog, Tamas; Baheti, Saurabh; Nie, Jinfu; Duan, Xiaohui; Hojo, Kaori; Kocher, Jean-Pierre; Dyck, Peter J; Klein, Christopher J

2014-08-01

DNA methyltransferase 1 (DNMT1) is essential for DNA methylation, gene regulation and chromatin stability. We previously discovered DNMT1 mutations cause hereditary sensory and autonomic neuropathy type 1 with dementia and hearing loss (HSAN1E; OMIM 614116). HSAN1E is the first adult-onset neurodegenerative disorder caused by a defect in a methyltransferase gene. HSAN1E patients appear clinically normal until young adulthood, then begin developing the characteristic symptoms involving central and peripheral nervous systems. Some HSAN1E patients also develop narcolepsy and it has recently been suggested that HSAN1E is allelic to autosomal dominant cerebellar ataxia, deafness, with narcolepsy (ADCA-DN; OMIM 604121), which is also caused by mutations in DNMT1. A hotspot mutation Y495C within the targeting sequence domain of DNMT1 has been identified among HSAN1E patients. The mutant DNMT1 protein shows premature degradation and reduced DNA methyltransferase activity. Herein, we investigate genome-wide DNA methylation at single-base resolution through whole-genome bisulfite sequencing of germline DNA in 3 pairs of HSAN1E patients and their gender- and age-matched siblings. Over 1 billion 75-bp single-end reads were generated for each sample. In the 3 affected siblings, overall methylation loss was consistently found in all chromosomes with X and 18 being most affected. Paired sample analysis identified 564,218 differentially methylated CpG sites (DMCs; P<0.05), of which 300 134 were intergenic and 264 084 genic CpGs. Hypomethylation was predominant in both genic and intergenic regions, including promoters, exons, most CpG islands, L1, L2, Alu, and satellite repeats and simple repeat sequences. In some CpG islands, hypermethylated CpGs outnumbered hypomethylated CpGs. In 201 imprinted genes, there were more DMCs than in non-imprinted genes and most were hypomethylated. Differentially methylated region (DMR) analysis identified 5649 hypomethylated and 1872

Proteomic analysis of trichloroethylene-induced alterations in expression, distribution, and interactions of SET/TAF-Iα and two SET/TAF-Iα-binding proteins, eEF1A1 and eEF1A2, in hepatic L-02 cells.

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Hong, Wen-Xu; Yang, Liang; Chen, Moutong; Yang, Xifei; Ren, Xiaohu; Fang, Shisong; Ye, Jinbo; Huang, Haiyan; Peng, Chaoqiong; Zhou, Li; Huang, Xinfeng; Yang, Fan; Wu, Desheng; Zhuang, Zhixiong; Liu, Jianjun

2012-09-01

Emerging evidence indicates that trichloroethylene (TCE) exposure causes severe hepatotoxicity. However, the mechanisms of TCE hepatotoxicity remain unclear. Recently, we reported that TCE exposure up-regulated the expression of the oncoprotein SET/TAF-Iα and SET knockdown attenuated TCE-induced cytotoxicity in hepatic L-02 cells. To decipher the function of SET/TAF-Iα and its contributions to TCE-induced hepatotoxicity, we employed a proteomic analysis of SET/TAF-Iα with tandem affinity purification to identify SET/TAF-Iα-binding proteins. We identified 42 novel Gene Ontology co-annotated SET/TAF-Iα-binding proteins. The identifications of two of these proteins (eEF1A1, elongation factor 1-alpha 1; eEF1A2, elongation factor 1-alpha 2) were confirmed by Western blot analysis and co-immunoprecipitation (Co-IP). Furthermore, we analyzed the effects of TCE on the expression, distribution and interactions of eEF1A1, eEF1A2 and SET in L-02 cells. Western blot analysis reveals a significant up-regulation of eEF1A1, eEF1A2 and two isoforms of SET, and immunocytochemical analysis reveals that eEF1A1 and SET is redistributed by TCE. SET is redistributed from the nucleus to the cytoplasm, while eFE1A1 is translocated from the cytoplasm to the nucleus. Moreover, we find by Co-IP that TCE exposure significantly increases the interaction of SET with eEF1A2. Our data not only provide insights into the physiological functions of SET/TAF-Iα and complement the SET interaction networks, but also demonstrate that TCE exposure induces alterations in the expression, distribution and interactions of SET and its binding partners. These alterations may constitute the mechanisms of TCE cytotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

Differences in total and allergen specific IgE during pregnancy compared with 1 month and 1 year post partum.

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Perry, Lee M; Ownby, Dennis R; Wegienka, Ganesa R; Peterson, Edward L; Woodcroft, Kimberly J; Joseph, Christine L; Johnson, Christine C

2009-10-01

Pregnancy alters the function of many body systems, including the immune system. However, little is known regarding the effect of pregnancy on maternal IgE levels or atopy. To determine whether pregnancy consistently influences serum levels of total or allergen specific IgE. Blood samples were obtained from 764 women during the third trimester of pregnancy and 1 month post partum. A third sample was obtained from 106 of these women 1 year post partum. Samples were analyzed for total and specific IgE to 8 regionally common allergens using a commercially available system. Sensitization was defined as an allergen specific IgE level of 0.35 kU of allergen per liter or higher to any allergen. Total IgE increased significantly post partum, both at 1 month (40.36 vs 35.37 IU/mL intrapartum; P = .001) and at 1 year (44.97 vs 37.00 IU/mL intrapartum; P = .005). Allergen specific IgE decreased significantly at 1 month for cat, dog, ragweed, timothy grass, and egg (P = .001 to P = .02) but not for dust mite, cockroach, or Alternaria (P = .15 to P = .90). Similar patterns of change in total and specific IgE were seen at 1 year. However, on average, only 3.5% of participants changed sensitization status to the individual allergens studied during the 1 year of observation. Compared with intrapartum levels, total IgE levels increased significantly at 1 month and 1 year post partum. Conversely, at the same time points, IgE levels specific for common allergens significantly declined to most but not all allergens. Few women changed their sensitization status over 1 year.

Microsomal prostaglandin E synthase-1 in rheumatic diseases

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Marina eKorotkova

2011-01-01

Full Text Available Microsomal prostaglandin E synthase-1 (mPGES-1 is a well recognized target for the development of novel anti-inflammatory drugs that can reduce symptoms of inflammation in rheumatic diseases and other inflammatory conditions. In this review, we focus on mPGES-1 in rheumatic diseases with the aim to cover the most recent advances in the understanding of mPGES-1 in rheumatoid arthritis, osteoarthritis and inflammatory myopathies. Novel findings regarding regulation of mPGES1 cell expression as well as enzyme inhibitors are also summarized.

Vaccination with Eimeria tenella elongation factor-1α recombinant protein induces protective immunity against E. tenella and E. maxima infections.

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Lin, Rui-Qing; Lillehoj, Hyun S; Lee, Seung Kyoo; Oh, Sungtaek; Panebra, Alfredo; Lillehoj, Erik P

2017-08-30

Avian coccidiosis is caused by multiple species of the apicomplexan protozoan, Eimeria, and is one of the most economically devastating enteric diseases for the poultry industry worldwide. Host immunity to Eimeria infection, however, is relatively species-specific. The ability to immunize chickens against different species of Eimeria using a single vaccine will have a major beneficial impact on commercial poultry production. In this paper, we describe the molecular cloning, purification, and vaccination efficacy of a novel Eimeria vaccine candidate, elongation factor-1α (EF-1α). One day-old broiler chickens were given two subcutaneous immunizations one week apart with E. coli-expressed E. tenella recombinant (r)EF-1α protein and evaluated for protection against challenge infection with E. tenella or E. maxima. rEF-1α-vaccinated chickens exhibited increased body weight gains, decreased fecal oocyst output, and greater serum anti-EF-1α antibody levels following challenge infection with either E. tenella or E. maxima compared with unimmunized controls. Vaccination with EF-1α may represent a new approach to inducing cross-protective immunity against avian coccidiosis in the field. Published by Elsevier B.V.

E2F1 transcription is induced by genotoxic stress through ATM/ATR activation.

Science.gov (United States)

Carcagno, Abel L; Ogara, María F; Sonzogni, Silvina V; Marazita, Mariela C; Sirkin, Pablo F; Ceruti, Julieta M; Cánepa, Eduardo T

2009-05-01

E2F1, a member of the E2F family of transcription factors, plays a critical role in controlling both cell cycle progression and apoptotic cell death in response to DNA damage and oncogene activation. Following genotoxic stresses, E2F1 protein is stabilized by phosphorylation and acetylation driven to its accumulation. The aim of the present work was to examine whether the increase in E2F1 protein levels observed after DNA damage is only a reflection of an increase in E2F1 protein stability or is also the consequence of enhanced transcription of the E2F1 gene. The data presented here demonstrates that UV light and other genotoxics induce the transcription of E2F1 gene in an ATM/ATR dependent manner, which results in increasing E2F1 mRNA and protein levels. After genotoxic stress, transcription of cyclin E, an E2F1 target gene, was significantly induced. This induction was the result of two well-differentiated effects, one of them dependent on de novo protein synthesis and the other on the protein stabilization. Our results strongly support a transcriptional effect of DNA damaging agents on E2F1 expression. The results presented herein uncover a new mechanism involving E2F1 in response to genotoxic stress.

Chimeras of Bet v 1 and Api g 1 reveal heterogeneous IgE responses in patients with birch pollen allergy.

Science.gov (United States)

Gepp, Barbara; Lengger, Nina; Bublin, Merima; Hemmer, Wolfgang; Breiteneder, Heimo; Radauer, Christian

2014-07-01

Characterization of IgE-binding epitopes of allergens and determination of their patient-specific relevance is crucial for the diagnosis and treatment of allergy. We sought to assess the contribution of specific surface areas of the major birch pollen allergen Bet v 1.0101 to binding IgE of individual patients. Four distinct areas of Bet v 1 representing in total 81% of its surface were grafted onto the scaffold of its homolog, Api g 1.0101, to yield the chimeras Api-Bet-1 to Api-Bet-4. The chimeras were expressed in Escherichia coli and purified. IgE binding of 64 sera from Bet v 1-sensitized subjects with birch pollen allergy was determined by using direct ELISA. Specificity was assessed by means of inhibition ELISA. rApi g 1.0101, Api-Bet-1, Api-Bet-2, Api-Bet-3, and Api-Bet-4 bound IgE from 44%, 89%, 80%, 78%, and 48% of the patients, respectively. By comparing the amount of IgE binding to the chimeras and to rApi g 1.0101, 81%, 70%, 75%, and 45% of the patients showed significantly enhanced IgE binding to Api-Bet-1, Api-Bet-2, Api-Bet-3, and Api-Bet-4, respectively. The minority (8%) of the sera revealed enhanced IgE binding exclusively to a single chimera, whereas 31% showed increased IgE binding to all 4 chimeras compared with rApi g 1.0101. The chimeras inhibited up to 70% of IgE binding to rBet v 1.0101, confirming the specific IgE recognition of the grafted regions. The Bet v 1-specific IgE response is polyclonal, and epitopes are spread across the entire Bet v 1 surface. Furthermore, the IgE recognition profile of Bet v 1 is highly patient specific. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

Measurements of sigma (e+e-→μ+-μ-+) in the energy range 1.2-3.0 GeV

International Nuclear Information System (INIS)

Alles-Borelli, V.; Bernardini, M.; Bollini, D.; Giusti, P.; Massam, T.; Monari, L.; Palmonari, F.; Valenti, G.; Zichichi, A.

1975-01-01

The analysis of 1466 events of the type e + e - →μ +- μ -+ , in the time-like range from 1.44 to 9.00 GeV 2 , shows that the absolute value of the cross-section and its energy dependence follow QED expectations within (+- 3.2%) and (+- 1.2%), respectively. (Auth.)

B1 Cell IgE Impedes Mast Cell-Mediated Enhancement of Parasite Expulsion through B2 IgE Blockade

OpenAIRE

Rebecca K. Martin; Sheela R. Damle; Yolander A. Valentine; Matthew P. Zellner; Briana N. James; Joseph C. Lownik; Andrea J. Luker; Elijah H. Davis; Martha M. DeMeules; Laura M. Khandjian; Fred D. Finkelman; Joseph F. Urban, Jr.; Daniel H. Conrad

2018-01-01

Helminth infection is known for generating large amounts of poly-specific IgE. Here we demonstrate that innate-like B1 cells are responsible for this IgE production during infection with the nematode parasites Nippostrongylus brasiliensis and Heligmosomoides polygyrus bakeri. In vitro analysis of B1 cell immunoglobulin class switch recombination to IgE demonstrated a requirement for anti-CD40 and IL-4 that was further enhanced when IL-5 was added or when the B1 source was helminth infected mi...

Identification of an ovine atadenovirus gene whose product activates the viral E2 promoter: possible involvement of E2F-1

International Nuclear Information System (INIS)

Kuemin, Daniel; Hofmann, Christian; Uckert, Wolfgang; Both, Gerald W.; Loeser, Peter

2004-01-01

Activation of the adenoviral E2 promoter is an early step in adenovirus gene expression. For members of the mast- and aviadenoviruses, this requires induction of the cellular transcription factor E2F by virally encoded gene products such as E1A, E4orf6/7 and orf22/GAM-1. The newly recognized genus atadenovirus, of which the ovine isolate OAdV is the prototype, lacks any sequence homology to those genes. To find a possible link between E2 promoter activation and OAdV gene expression, we utilized a screening method to search for genes within the OAdV genome that were capable of stimulating the viral E2 promoter. One such gene, E43, was identified within the proposed E4 region toward the right-hand end of the OAdV genome. The E43 gene product was also found to be capable of stimulating E2F-1-dependent gene expression. A closer inspection of the E2 promoter revealed the presence of a non-palindromic E2F binding site within the OAdV E2 promoter. Mutation of this site markedly reduced both E2F-1- and E43-dependent promoter activation. Moreover, a direct protein-protein interaction of the E43 gene product with E2F, but not with the retinoblastoma protein pRb, suggested a possible cooperation between these two proteins in activating the E2 promoter. The importance of the E43 gene product for virus replication is also underlined by the finding that an OAdV recombinant with a functionally inactivated E43 gene showed severely inhibited virus growth

Structural model of the hUbA1-UbcH10 quaternary complex: in silico and experimental analysis of the protein-protein interactions between E1, E2 and ubiquitin.

Directory of Open Access Journals (Sweden)

Stefania Correale

Full Text Available UbcH10 is a component of the Ubiquitin Conjugation Enzymes (Ubc; E2 involved in the ubiquitination cascade controlling the cell cycle progression, whereby ubiquitin, activated by E1, is transferred through E2 to the target protein with the involvement of E3 enzymes. In this work we propose the first three dimensional model of the tetrameric complex formed by the human UbA1 (E1, two ubiquitin molecules and UbcH10 (E2, leading to the transthiolation reaction. The 3D model was built up by using an experimentally guided incremental docking strategy that combined homology modeling, protein-protein docking and refinement by means of molecular dynamics simulations. The structural features of the in silico model allowed us to identify the regions that mediate the recognition between the interacting proteins, revealing the active role of the ubiquitin crosslinked to E1 in the complex formation. Finally, the role of these regions involved in the E1-E2 binding was validated by designing short peptides that specifically interfere with the binding of UbcH10, thus supporting the reliability of the proposed model and representing valuable scaffolds for the design of peptidomimetic compounds that can bind selectively to Ubcs and inhibit the ubiquitylation process in pathological disorders.

Production of thermostable glucoamylase by newly isolated Aspergillus flavus A 1.1 and Thermomyces lanuginosus A 13.37 Produção e glucoamilase por Aspergillus flavus A1.1 e Thermomyces lanuginosus A13.37

Directory of Open Access Journals (Sweden)

Eleni Gomes

2005-03-01

isolados a partir de amostras de solo agrícola, tubérculos e de material em compostagem, duas foram selecionadas em função da capacidade de crescer em meio líquido contendo amido como única fonte de carbono, a 45ºC, e produzir consideráveis quantidades de glucoamilase. Essas linhagens, identificadas como Aspergillus flavus A1.1 e Thermomyces lanuginosus A13.37, foram utilizadas para desenvolvimento de experimentos para avaliar os efeitos do tipo de amido (milho e mandioca, do pH inicial do meio de cultura (4,0; 5,0 e 6,0 e da temperatura de incubação (40 e 45ºC, em um modelo fatorial (2x3x2, sobre a produção da glucoamilase. O tipo de amido usado como fonte de carbono para o cultivo dos fungos influenciou significativamente a produção de glucoamilase por A. flavus, sendo obtida uma maior quantidade da enzima em meio contendo amido de mandioca do que em meio com amido de milho. A produção da enzima por T. lanuginosus também foi maior em meio contendo amido de mandioca, porém, a diferença não foi estatisticamente significativa. As atividades enzimáticas sobre amido (0,3%, maltose (0,3% ou sobre mistura de 0,3% de amido com 0,1% de maltose, indicaram que as enzimas de Aspergillus hidrolisaram, preferencialmente, o amido, embora tenham mostrado atividade considerável sobre a maltose. A maior liberação de glicose a partir da mistura de substratos sugeriu que o fungo em questão possa secretar dois tipos diferentes de enzimas. Enzimas produzidas por T. lanuginosus hidrolisaram o amido e a maltose e não liberaram maiores teores de glicose quando o substrato constou de mistura de amido e maltose. As enzimas de Aspergillus e Thermomyces apresentaram elevada temperatura ótima de atividade (65 e 70ºC, respectivamente com boa termoestabilidade na ausência de substrato (manutenção de 50% da atividade por 5 e 8h respectivamente, além de estabilidade em ampla faixa de pH. Os resultados apresentados indicam uma importante fonte alternativa de glucoamilase

E3B1, a human homologue of the mouse gene product Abi-1, sensitizes activation of Rap1 in response to epidermal growth factor

International Nuclear Information System (INIS)

Jenei, Veronika; Andersson, Tommy; Jakus, Judit; Dib, Karim

2005-01-01

E3B1, a human homologue of the mouse gene product Abi-1, has been implicated in growth-factor-mediated regulation of the small GTPases p21 Ras and Rac. E3b1 is a regulator of Rac because it can form a complex with Sos-1 and eps8, and such a Sos-1-e3B1-eps8 complex serves as a guanine nucleotide exchange factor for Rac. In the present study, we found that overexpression of e3B1 in NIH3T3/EGFR cells sensitized EGF-induced activation of Rac1, whereas it had no impact on EGF-induced activation of p21 Ras . Remarkably, we found that EGF-induced activation of the p21 Ras -related GTPase Rap1 was also sensitized in NIH3T3/EGFR-e3B1 cells. Thus, in NIH3T3/EGFR-e3B1 cells, maximal EGF-induced activation of Rap1 occurs with a dose of EGF much lower than in NIH3T3/EGFR cells. We also report that overexpression of e3B1 in NIH3T3/EGFR cells renders EGF-induced activation of Rap1 completely dependent on Src tyrosine kinases but not on c-Abl. However, EGF-induced tyrosine phosphorylation of the Rap GEF C3G occurred regardless of whether e3B1 was overexpressed or not, and this did not involve Src tyrosine kinases. Accordingly, we propose that overexpression of e3B1 in NIH3T3/EGFR cells leads to mobilization of Src tyrosine kinases that participate in EGF-induced activation of Rap1 and inhibition of cell proliferation

Data of evolutionary structure change: 1RAAA-3GD5E [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 1RAAA-3GD5E 1RAA 3GD5 A E ANPLYQKHIISINDLSRDDLNLVLATAAKLKANPQPELL...LRDPFEAARGAHILYTDVWTHRLQLFEQYQINAAL------------LNC--AAAEAIVLHCLPAHRGEEITDEVMEGPRS...ID> 0 1RAA A 1RAAA 1RAA A 1RAAA1RAA A 1RAAA TEFSGNVPVLN

E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1)

DEFF Research Database (Denmark)

Hsu, Jerry Y; Reimann, Julie D R; Sørensen, Claus S

2002-01-01

. At the G1-S transition, hEmi1 is transcriptionally induced by the E2F transcription factor, much like cyclin A. hEmi1 overexpression accelerates S phase entry and can override a G1 block caused by overexpression of Cdh1 or the E2F-inhibitor p105 retinoblastoma protein (pRb). Depleting cells of hEmi1...

Lettuce and rhizosphere microbiome responses to growth promoting Pseudomonas species under field conditions.

Science.gov (United States)

Cipriano, Matheus A P; Lupatini, Manoeli; Lopes-Santos, Lucilene; da Silva, Márcio J; Roesch, Luiz F W; Destéfano, Suzete A L; Freitas, Sueli S; Kuramae, Eiko E

2016-12-01

Plant growth promoting rhizobacteria are well described and recommended for several crops worldwide. However, one of the most common problems in research into them is the difficulty in obtaining reproducible results. Furthermore, few studies have evaluated plant growth promotion and soil microbial community composition resulting from bacterial inoculation under field conditions. Here we evaluated the effect of 54 Pseudomonas strains on lettuce (Lactuca sativa) growth. The 12 most promising strains were phylogenetically and physiologically characterized for plant growth-promoting traits, including phosphate solubilization, hormone production and antagonism to pathogen compounds, and their effect on plant growth under farm field conditions. Additionally, the impact of beneficial strains on the rhizospheric bacterial community was evaluated for inoculated plants. The strains IAC-RBcr4 and IAC-RBru1, with different plant growth promoting traits, improved lettuce plant biomass yields up to 30%. These two strains also impacted rhizosphere bacterial groups including Isosphaera and Pirellula (phylum Planctomycetes) and Acidothermus, Pseudolabrys and Singusphaera (phylum Actinobacteria). This is the first study to demonstrate consistent results for the effects of Pseudomonas strains on lettuce growth promotion for seedlings and plants grown under tropical field conditions. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Modulation of thyroid hormone receptor transactivation by the early region 1A (E1A-like inhibitor of differentiation 1 (EID1

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Diana Vargas

2008-01-01

Full Text Available Transcriptional activation (TA mediated by the effect of thyroid hormones on target genes requires co-activator proteins such as the early region 1A (E1A associated 300 kDa binding protein (p300 and the cAMP response element binding protein (CREB binding protein (CBP, known as the p300/CBP complex, which acetylate histones 3 and 4 to allow transcriptional machinery access to the target gene promoter. Little is known on the role of p300 in thyroid hormone receptor (TR mediated TA but the E1A-like inhibitor of differentiation 1 (EID1, an inhibitor of p300 histone acetyltransferase (HAT, is a functional homolog of E1A and may inhibit myogenic differentiation factor D (MyoD transcriptional activity and reduces muscle cell differentiation. We evaluated the influence of EID1 on TR-mediated transcriptional activity using transfection and mammalian two-hybrid studies to show that EID1 may partially reduces TA activity of the TR receptor, probably due to p300 blockage since EID1 mutants cannot reduce TR-mediated TA. The EID1 does not affect the function of p160 co-activator proteins (160 kDa proteins of steroid receptor co-activators and is functionally independent of co-repressor proteins or TR binding. Summarizing, EID1 reduces TR-mediated transcriptional activity by blocking p300 and may play an important role in thyroid receptor activity in muscle and other tissues.

E2F1-mediated human POMC expression in ectopic Cushing's syndrome.

Science.gov (United States)

Araki, Takako; Liu, Ning-Ai; Tone, Yukiko; Cuevas-Ramos, Daniel; Heltsley, Roy; Tone, Masahide; Melmed, Shlomo

2016-11-01

Cushing's syndrome is caused by excessive adrenocorticotropic hormone (ACTH) secretion derived from pituitary corticotroph tumors (Cushing disease) or from non-pituitary tumors (ectopic Cushing's syndrome). Hypercortisolemic features of ectopic Cushing's syndrome are severe, and no definitive treatment for paraneoplastic ACTH excess is available. We aimed to identify subcellular therapeutic targets by elucidating transcriptional regulation of the human ACTH precursor POMC (proopiomelanocortin) and ACTH production in non-pituitary tumor cells and in cell lines derived from patients with ectopic Cushing's syndrome. We show that ectopic hPOMC transcription proceeds independently of pituitary-specific Tpit/Pitx1 and demonstrate a novel E2F1-mediated transcriptional mechanism regulating hPOMC We identify an E2F1 cluster binding to the proximal hPOMC promoter region (-42 to +68), with DNA-binding activity determined by the phosphorylation at Ser-337. hPOMC mRNA expression in cancer cells was upregulated (up to 40-fold) by the co-expression of E2F1 and its heterodimer partner DP1. Direct and indirect inhibitors of E2F1 activity suppressed hPOMC gene expression and ACTH by modifying E2F1 DNA-binding activity in ectopic Cushing's cell lines and primary tumor cells, and also suppressed paraneoplastic ACTH and cortisol levels in xenografted mice. E2F1-mediated hPOMC transcription is a potential target for suppressing ACTH production in ectopic Cushing's syndrome. © 2016 Society for Endocrinology.

Use of Saccharomyces cerevisiae yeasts in the chemo selective bioreduction of (1E,4E)-1,5-bis(4-methoxyphenyl)-1,4-pentadien-3-one in biphasic system

International Nuclear Information System (INIS)

Schaefer, Cesar A.; Silva, Vanessa D.; Nascimento, Maria da G.; Stambuk, Boris U.

2013-01-01

This work describes the chemoselective bioreduction of (1E,4E)-1,5-bis(4-methoxyphenyl)- 1,4-pentadien-3-one (1) mediated by baker’s yeast (BY, Saccharomyces cerevisiae cells) in an aqueous/organic solvent biphasic system. The biotransformation of this compound was chemoselective and formed only the corresponding saturated ketone 1,5-bis(4-methoxyphenyl)- 3-pentanone (2). The influence of various factors which may alter the bioreduction of 1, such as the type and percentage of co-solvents, use of six different S. cerevisiae yeast samples (four commercial and two industrial), variations in the substrate and yeast concentrations, temperature, pH and volume of aqueous and organic phases, was investigated. The best reaction conditions were 66.7 g L −1 of Fleischmann BY, 8.3 × 10 −3 mol L −1 of substrate, pH 6.5 at 35 deg C in the presence of 2.5% (v/v) of N,N-dimethyl sulfoxide (DMSO) as an additive and a V aq /V org ratio of 70/30. Under these conditions, the product 2 was recovered in conversions of 82% in 5 h reaction. (author)

Use of Saccharomyces cerevisiae yeasts in the chemo selective bioreduction of (1E,4E)-1,5-bis(4-methoxyphenyl)-1,4-pentadien-3-one in biphasic system

Energy Technology Data Exchange (ETDEWEB)

Schaefer, Cesar A.; Silva, Vanessa D.; Nascimento, Maria da G., E-mail: maria.nascimento@ufsc.br [Departamento de Quimica, Universidade Federal de Santa Catarina, Florianopolis-SC (Brazil); Stambuk, Boris U. [Departamento de Bioquimica, Universidade Federal de Santa Catarina, Florianopolis-SC (Brazil)

2013-07-15

This work describes the chemoselective bioreduction of (1E,4E)-1,5-bis(4-methoxyphenyl)- 1,4-pentadien-3-one (1) mediated by baker's yeast (BY, Saccharomyces cerevisiae cells) in an aqueous/organic solvent biphasic system. The biotransformation of this compound was chemoselective and formed only the corresponding saturated ketone 1,5-bis(4-methoxyphenyl)- 3-pentanone (2). The influence of various factors which may alter the bioreduction of 1, such as the type and percentage of co-solvents, use of six different S. cerevisiae yeast samples (four commercial and two industrial), variations in the substrate and yeast concentrations, temperature, pH and volume of aqueous and organic phases, was investigated. The best reaction conditions were 66.7 g L{sup -1} of Fleischmann BY, 8.3 Multiplication-Sign 10{sup -3} mol L{sup -1} of substrate, pH 6.5 at 35 deg C in the presence of 2.5% (v/v) of N,N-dimethyl sulfoxide (DMSO) as an additive and a V{sub aq}/V{sub org} ratio of 70/30. Under these conditions, the product 2 was recovered in conversions of 82% in 5 h reaction. (author)

DNA Damage Reduces the Quality, but Not the Quantity of Human Papillomavirus 16 E1 and E2 DNA Replication.

Science.gov (United States)

Bristol, Molly L; Wang, Xu; Smith, Nathan W; Son, Minkyeong P; Evans, Michael R; Morgan, Iain M

2016-06-22

Human papillomaviruses (HPVs) are causative agents in almost all cervical carcinomas. HPVs are also causative agents in head and neck cancer, the cases of which are increasing rapidly. Viral replication activates the DNA damage response (DDR) pathway; associated proteins are recruited to replication foci, and this pathway may serve to allow for viral genome amplification. Likewise, HPV genome double-strand breaks (DSBs) could be produced during replication and could lead to linearization and viral integration. Many studies have shown that viral integration into the host genome results in unregulated expression of the viral oncogenes, E6 and E7, promoting HPV-induced carcinogenesis. Previously, we have demonstrated that DNA-damaging agents, such as etoposide, or knocking down viral replication partner proteins, such as topoisomerase II β binding protein I (TopBP1), does not reduce the level of DNA replication. Here, we investigated whether these treatments alter the quality of DNA replication by HPV16 E1 and E2. We confirm that knockdown of TopBP1 or treatment with etoposide does not reduce total levels of E1/E2-mediated DNA replication; however, the quality of replication is significantly reduced. The results demonstrate that E1 and E2 continue to replicate under genomically-stressed conditions and that this replication is mutagenic. This mutagenesis would promote the formation of substrates for integration of the viral genome into that of the host, a hallmark of cervical cancer.

DNA Damage Reduces the Quality, but Not the Quantity of Human Papillomavirus 16 E1 and E2 DNA Replication

Directory of Open Access Journals (Sweden)

Molly L. Bristol

2016-06-01

Full Text Available Human papillomaviruses (HPVs are causative agents in almost all cervical carcinomas. HPVs are also causative agents in head and neck cancer, the cases of which are increasing rapidly. Viral replication activates the DNA damage response (DDR pathway; associated proteins are recruited to replication foci, and this pathway may serve to allow for viral genome amplification. Likewise, HPV genome double-strand breaks (DSBs could be produced during replication and could lead to linearization and viral integration. Many studies have shown that viral integration into the host genome results in unregulated expression of the viral oncogenes, E6 and E7, promoting HPV-induced carcinogenesis. Previously, we have demonstrated that DNA-damaging agents, such as etoposide, or knocking down viral replication partner proteins, such as topoisomerase II β binding protein I (TopBP1, does not reduce the level of DNA replication. Here, we investigated whether these treatments alter the quality of DNA replication by HPV16 E1 and E2. We confirm that knockdown of TopBP1 or treatment with etoposide does not reduce total levels of E1/E2-mediated DNA replication; however, the quality of replication is significantly reduced. The results demonstrate that E1 and E2 continue to replicate under genomically-stressed conditions and that this replication is mutagenic. This mutagenesis would promote the formation of substrates for integration of the viral genome into that of the host, a hallmark of cervical cancer.

DOE-2 supplement: Version 2.1E

Energy Technology Data Exchange (ETDEWEB)

Winkelmann, F.C.; Birdsall, B.E.; Buhl, W.F.; Ellington, K.L.; Erdem, A.E. [Lawrence Berkeley Lab., CA (United States); Hirsch, J.J.; Gates, S. [Hirsch (James J.) and Associates, Camarillo, CA (United States)

1993-11-01

This publication updates the DOE-2 Supplement form version 2.1D to version to 2.1E. It contains detailed discussions and instructions for using the features and enhancements introduced into the 2.1B, 2.1C, 2.1D, and 2.1E versions of the program. The building description section contains information on input functions in loads and systems, hourly report frequencies, saving files of hourly output for post processing, sharing hourly report data among program modules, the metric option, and input macros and general library features. The loads section contains information on sunspaces, sunspace modeling, window management and solar radiation, daylighting, trombe walls, fixed shades, fins and overhangs, shade schedules, self shades, heat distribution from lights, the Sherman-Grimsrud infiltrations method. terrain and height modification to wind speed, floor multipliers and interior wall types, improved exterior infrared radiation loss calculation, improved outside air film conductance calculation, window library, window frames, and switchable glazing. The systems section contains information on energy end use and meters, powered induction units, a packaged variable volume -- variable temperature system, a residential variable volume -- variable temperature system, air source heat pump enhancements, water loop heat pump enhancements, variable speed electric heat pump, gas heat pumps, hot water heaters, evaporative cooling, total gas solid-desiccant systems, add on desiccant cooling, water cooled condensers, evaporative precoolers outside air economizer control, optimum fan start, heat recovery from refrigerated case work, night ventilation, baseboard heating, moisture balance calculations, a residential natural ventilation algorithm, improved cooling coil model, system sizing and independent cooling and heating sizing ratios. The plant section contains information on energy meters, gas fired absorption chillers, engine driven compressor chillers, and ice energy storage.

Níveis das vitaminas A e E em dietas de frangos de corte de 1 a 42 dias de idade Levels of vitamins A and E on diets of broilers from 1 to 42 days

Directory of Open Access Journals (Sweden)

Geni Salete de Toledo

2006-04-01

Full Text Available O presente estudo foi conduzido no Setor de Avicultura do Departamento de Zootecnia da Universidade Federal de Santa Maria. Através deste experimento objetivou-se, avaliar uma possível relação entre diferentes níveis das vitaminas A (Retinol e E (Tocoferol, e o efeito destes níveis no desempenho de frangos de corte nas fases de 1-21 e de 1-42 dias de idade. Foram utilizados 990 pintos de corte de um dia de idade, machos, da linhagem Ross. O trabalho foi composto de nove tratamentos, com cinco repetições de 22 aves cada. O delineamento experimental foi em blocos dirigidos, em um fatorial de 32 (3 níveis vs. 2 vitaminas. Os níveis utilizados das vitaminas A e E por kg de dieta foram 5.000; 10.000 e 15.000UI e 10; 20 e 30mg respectivamente. Os parâmetros avaliados foram: consumo alimentar, peso corporal, conversão alimentar e mortalidade. O consumo de ração, o peso corporal e a conversão alimentar não foram afetados pelo aumento ou diminuição dos níveis médios das vitaminas estudadas. Baseados nestes resultados, conclui-se que as vitaminas A e E no nível baixo ou seja 50% abaixo dos níveis utilizados nas agro-industrias do sul do país, não deprimem o crescimento dos frangos quando comparados com os níveis médio e alto, o que pode levar a uma diminuição nos custos de produção.This experimental research was conducted at the Poultry Section of the Animal Science Department at the Federal University of Santa Maria. The objective of this work was to evaluate the interactions between different levels of vitamins A (Retinol and E (tocoferol, and their effect on broilers performance in two periods: 1-21 and 1-42 days of age. A total of 990 ROSS day-old male chicks were set. The trial was composed by 9 treatments, with 5 replicates of 22 birds each. An experimental design in blocks was employed in a factorial 32 (three levels of two vitamins. The levels of vitamins A and E were 5,000; 10,000 and 15,000UI and 10; 20 and 30mg kg

(1E,2E-1,2-Bis(2,2-diphenylhydrazin-1-ylideneethane

Directory of Open Access Journals (Sweden)

Angel Mendoza

2010-09-01

Full Text Available In the crystal structure of the title compound, C26H22N4, the molecule is located on an inversion centre and shows an E configuration with respect to each C=N bond. The dihedral angle between the phenyl rings in the diphenylhydrazone group is 83.69 (11°. These two rings make dihedral angles of 30.53 (15 and 84.53 (16° with the central N—N=C—C=N—N dihydrazonoethane plane. Intermolecular C—H...π interactions are observed.

Data of evolutionary structure change: 1RAAA-3E2PM [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 1RAAA-3E2PM 1RAA 3E2P A M ANPLYQKHIISINDLSRDDLNLVLATAAKLKANPQ----... 1RAA A 1RAAA KANPQ----PELLK 1 1RAA A 1RAAA... 345 ILE CA 291 1RAA A 1RAAA...dbChain> 1RAAA TEFSGNVPVLN HHHH

Transcriptional regulation of human RANK ligand gene expression by E2F1

International Nuclear Information System (INIS)

Hu Yan; Sun Meng; Nadiminty, Nagalakshmi; Lou Wei; Pinder, Elaine; Gao, Allen C.

2008-01-01

Receptor activator of nuclear factor kappa B ligand (RANKL) is a critical osteoclastogenic factor involved in the regulation of bone resorption, immune function, the development of mammary gland and cardiovascular system. To understand the transcriptional regulation of RANKL, we amplified and characterized a 1890 bp 5'-flanking sequence of human RANKL gene (-1782 bp to +108 bp relative to the transcription start site). Using a series of deletion mutations of the 1890 bp RANKL promoter, we identified a 72 bp region (-172 to -100 bp) mediating RANKL basal transcriptional activity. Sequence analysis revealed a putative E2F binding site within this 72 bp region in the human RANKL promoter. Overexpression of E2F1 increased RANKL promoter activity, while down-regulation of E2F1 expression by small interfering RNA decreased RANKL promoter activity. RT-PCR and enzyme linked immunosorbent assays (ELISA) further demonstrated that E2F1 induced the expression of RANKL. Electrophoretic gel mobility shift assays (EMSA) and antibody competition assays confirmed that E2F1 proteins bind to the consensus E2F binding site in the RANKL promoter. Mutation of the E2F consensus binding site in the RANKL promoter profoundly reduced the basal promoter activity and abolished the transcriptional modulation of RANKL by E2F1. These results suggest that E2F1 plays an important role in regulating RANKL transcription through binding to the E2F consensus binding site

Apolipoprotein E levels in cerebrospinal fluid and the effects of ABCA1 polymorphisms

Directory of Open Access Journals (Sweden)

Mayo Kevin

2007-04-01

Full Text Available Abstract Background Animal studies suggest that brain apolipoprotein E (apoE levels influence amyloid-β (Aβ deposition and thus risk for Alzheimer's disease (AD. We have previously demonstrated that deletion of the ATP-binding cassette A1 transporter (ABCA1 in mice causes dramatic reductions in brain and cerebrospinal fluid (CSF apoE levels and lipidation. To examine whether polymorphisms in ABCA1 affect CSF apoE levels in humans, we measured apoE in CSF taken from 168 subjects who were 43 to 91 years old and were either cognitively normal or who had mild AD. We then genotyped the subjects for ten previously identified ABCA1 single nucleotide polymorphisms (SNPs. Results In all subjects, the mean CSF apoE level was 9.09 μg/ml with a standard deviation of 2.70 μg/ml. Levels of apoE in CSF samples taken from the same individual two weeks apart were strongly correlated (r2 = 0.93, p APOE genotype, gender or race. Average apoE levels increased with age by ~0.5 μg/ml per 10 years (r2 = 0.05, p = 0.003. We found no significant associations between CSF apoE levels and the ten ABCA1 SNPs we genotyped. Moreover, in a separate sample of 1225 AD cases and 1431 controls, we found no association between the ABCA1 SNP rs2230806 and AD as has been previously reported. Conclusion We found that CSF apoE levels vary widely between individuals, but are stable within individuals over a two-week interval. AD status, APOE genotype, gender and race do not affect CSF apoE levels, but average CSF apoE levels increase with age. Given the lack of association between CSF apoE levels and genotypes for the ABCA1 SNPs we examined, either these SNPs do not affect ABCA1 function or if they do, they do not have strong effects in the CNS. Finally, we find no evidence for an association between the ABCA1 SNP rs2230806 and AD in a large sample set.

Transcriptome of E. coli K1 bound to human brain microvascular endothelial cells

OpenAIRE

Xie, Yi; Parthasarathy, Geetha; Di Cello, Francescopaolo; Teng, Ching-Hao; Paul-Satyaseela, Maneesh; Kim, Kwang Sik

2007-01-01

Escherichia coli K1 is the most common Gram-negative organism causing neonatal meningitis. Binding to human brain microvascdular endothelial cells (HBMEC) is an essential step for E. coli K1 traversal of the blood-brain barrier. In this study, we examined expression profiles of E. coli K1 strain RS218 during its binding to HBMEC. Comparison of HBMEC-bound E. coli K1 with collagen-bound E. coli revealed more than one hundred genes whose expression patterns were significantly changed in HBMEC-b...

Modulation of the E2F1-driven cancer cell fate by the DNA damage response machinery and potential novel E2F1 targets in osteosarcomas

DEFF Research Database (Denmark)

Liontos, Michalis; Niforou, Katerina; Velimezi, Georgia

2009-01-01

Osteosarcoma is the most common primary bone cancer. Mutations of the RB gene represent the most frequent molecular defect in this malignancy. A major consequence of this alteration is that the activity of the key cell cycle regulator E2F1 is unleashed from the inhibitory effects of pRb. Studies...... in a clinical setting of human primary osteosarcomas and in E2F1-inducible osteosarcoma cell line models that are wild-type and deficient for p53. Collectively, our data demonstrated that high E2F1 levels exerted a growth-suppressing effect that relied on the integrity of the DNA damage response network...

Identification and characterization of multiple conserved nuclear localization signals within adenovirus E1A

Energy Technology Data Exchange (ETDEWEB)

Marshall, Kris S.; Cohen, Michael J.; Fonseca, Greg J.; Todorovic, Biljana; King, Cason R. [Department of Microbiology and Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada); Yousef, Ahmed F. [Department of Chemical and Environmental Engineering, Masdar Institute, Abu Dhabi (United Arab Emirates); Zhang, Zhiying [College of Animal Science and Technologies, Northwest A and F University, Yangling, Shaanxi 712100 (China); Mymryk, Joe S., E-mail: jmymryk@uwo.ca [Department of Microbiology and Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada); Department of Oncology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada)

2014-04-15

The human adenovirus 5 (HAdV-5) E1A protein has a well defined canonical nuclear localization signal (NLS) located at its C-terminus. We used a genetic assay in the yeast Saccharomyces cerevisiae to demonstrate that the canonical NLS is present and functional in the E1A proteins of each of the six HAdV species. This assay also detects a previously described non-canonical NLS within conserved region 3 and a novel active NLS within the N-terminal/conserved region 1 portion of HAdV-5 E1A. These activities were also present in the E1A proteins of each of the other five HAdV species. These results demonstrate that, despite substantial differences in primary sequence, HAdV E1A proteins are remarkably consistent in that they contain one canonical and two non-canonical NLSs. By utilizing independent mechanisms, these multiple NLSs ensure nuclear localization of E1A in the infected cell. - Highlights: • HAdV E1A uses multiple mechanisms for nuclear import. • We identified an additional non-canonical NLS in the N-terminal/CR1 portion of E1A. • The new NLS does not contact importin-alpha directly. • All NLSs are functionally conserved in the E1A proteins of all 6 HAdV species.

Religiosidade, juventude e sexualidade: entre a autonomia e a rigidez1

Science.gov (United States)

Silva, Cristiane Gonçalves da; Santos, Alessandro Oliveira; Licciardi, Daniele Carli; Paiva, Vera; Parker, Richard

2009-01-01

Esse artigo descreve como jovens religiosos e autoridades religiosas de sua comunidade compreendem a sexualidade, considerando suas experiências pessoais e como membros de comunidades religiosas. A análise pretende contribuir para que políticas públicas dedicadas à promoção da saúde sexual da juventude considerem a religiosidade, no contexto de um estado laico e da promoção do direito à prevenção. Foram realizadas 26 entrevistas abertas e semidirigidas em diferentes comunidades da região metropolitana da cidade de São Paulo (comunidades católicas, da umbanda, do candomblé e de diferentes denominações evangélicas) sobre iniciação sexual, casamento, gravidez, contracepção e prevenção das DST/Aids, homossexualidade, aborto e direitos humanos. Observou-se como jovens e autoridades religiosas convivem com a tensão entre tradição e modernidade e os distintos discursos sobre a sexualidade. Como sujeitos religiosos (do discurso religioso) e sujeitos sexuais (de discursos sobre sexualidade), devem ser incorporados pelos programas como sujeitos de direito nos termos de sua religiosidade. PMID:21886456

Observation of unexpectedly small E1 moments in sup 224 Ra

Energy Technology Data Exchange (ETDEWEB)

Poynter, R.J.; Butler, P.A.; Clarkson, N.; Hoare, T.H.; Jones, G.D.; White, C.A. (Liverpool Univ. (UK). Oliver Lodge Lab.); Cline, D. (Rochester Univ., NY (USA). Nuclear Structure Research Lab.); Connell, K.A.; Cunningham, R.A.; Simpson, J. (Science and Engineering Research Council, Daresbury (UK). Daresbury Lab.); Goettig, L. (Warsaw Univ. (Poland). Inst. Fizyki Doswiadczalnej); Hughes, J.R.; Jarvis, N.S.; Mullins, S.M.; Wadsworth, R.; Watson, D.L. (York Univ. (UK). Dept. of Physics); Juutinen, S. (Jyvaeskylae Univ. (Finland). Dept. of Physics); Pass, C.N. (Oxford Univ. (UK). Dept. of Nuclear Physics)

1989-12-14

The {alpha}-decay of {sup 228}Th and the reaction {sup 226}Ra({sup 58}Ni, {sup 60}Ni){sup 224}Ra have been employed to populate states in {sup 224}Ra up to I{sup {pi}}=12{sup +}. Values of the intrinsic electric dipole moment vertical strokeQ{sub 1}vertical stroke have been deduced from the observed B(E1)/B(E2) branching ratios. These values are < or approx.0.1 e fm for spins up to I{sup {pi}}=9{sup -}, and are thus smaller than those in {sup 218,220}Ra or {sup 226}Ra. The behaviour of Q{sub 1} suggests that shell effects are important in this mass region, although theoretical calculations which include these effects do not reproduce the observed pattern. (orig.).

The full-length E1-circumflexE4 protein of human papillomavirus type 18 modulates differentiation-dependent viral DNA amplification and late gene expression

International Nuclear Information System (INIS)

Wilson, Regina; Ryan, Gordon B.; Knight, Gillian L.; Laimins, Laimonis A.; Roberts, Sally

2007-01-01

Activation of the productive phase of the human papillomavirus (HPV) life cycle in differentiated keratinocytes is coincident with high-level expression of E1-circumflexE4 protein. To determine the role of E1-circumflexE4 in the HPV replication cycle, we constructed HPV18 mutant genomes in which expression of the full-length E1-circumflexE4 protein was abrogated. Undifferentiated keratinocytes containing mutant genomes showed enhanced proliferation when compared to cells containing wildtype genomes, but there were no differences in maintenance of viral episomes. Following differentiation, cells with mutant genomes exhibited reduced levels of viral DNA amplification and late gene expression, compared to wildtype genome-containing cells. This indicates that HPV18 E1-circumflexE4 plays an important role in regulating HPV late functions, and it may also function in the early phase of the replication cycle. Our finding that full-length HPV18 E1-circumflexE4 protein plays a significant role in promoting viral genome amplification concurs with a similar report with HPV31, but is in contrast to an HPV11 study where viral DNA amplification was not dependent on full-length E1-circumflexE4 expression, and to HPV16 where only C-terminal truncations in E1-circumflexE4 abrogated vegetative genome replication. This suggests that type-specific differences exist between various E1-circumflexE4 proteins

Induction of DNA synthesis and apoptosis are separable functions of E2F-1

DEFF Research Database (Denmark)

Phillips, A C; Bates, S; Ryan, K M

1997-01-01

The family of E2F transcription factors have an essential role in mediating cell cycle progression, and recently, one of the E2F protein family, E2F-1, has been shown to participate in the induction of apoptosis. Cooperation between E2F and the p53 tumor suppressor protein in this apoptotic...... response had led to the suggestion that cell cycle progression induced by E2F-1 expression provides an apoptotic signal when placed in conflict with an arrest to cell cycle progression, such as provided by p53. We show here that although apoptosis is clearly enhanced by p53, E2F-1 can induce significant...... apoptosis in the absence of p53. Furthermore, this apoptotic function of E2F-1 is separable from the ability to accelerate entry into DNA synthesis. Analysis of E2F-1 mutants indicates that although DNA-binding is required, transcriptional transactivation is not necessary for the induction of apoptosis by E...

Neurite outgrowth mediated by translation elongation factor eEF1A1: a target for antiplatelet agent cilostazol.

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Kenji Hashimoto

Full Text Available Cilostazol, a type-3 phosphodiesterase (PDE3 inhibitor, has become widely used as an antiplatelet drug worldwide. A recent second Cilostazol Stroke Prevention Study demonstrated that cilostazol is superior to aspirin for prevention of stroke after an ischemic stroke. However, its precise mechanisms of action remain to be determined. Here, we report that cilostazol, but not the PDE3 inhibitors cilostamide and milrinone, significantly potentiated nerve growth factor (NGF-induced neurite outgrowth in PC12 cells. Furthermore, specific inhibitors for the endoplasmic reticulum protein inositol 1,4,5-triphosphate (IP(3 receptors and several common signaling pathways (PLC-γ, PI3K, Akt, p38 MAPK, and c-Jun N-terminal kinase (JNK, and the Ras/Raf/ERK/MAPK significantly blocked the potentiation of NGF-induced neurite outgrowth by cilostazol. Using a proteomics analysis, we identified that levels of eukaryotic translation elongation factor eEF1A1 protein were significantly increased by treatment with cilostazol, but not cilostamide, in PC12 cells. Moreover, the potentiating effects of cilostazol on NGF-induced neurite outgrowth were significantly antagonized by treatment with eEF1A1 RNAi, but not the negative control of eEF1A1. These findings suggest that eEF1A1 and several common cellular signaling pathways might play a role in the mechanism of cilostazol-induced neurite outgrowth. Therefore, agents that can increase the eEF1A1 protein may have therapeutic relevance in diverse conditions with altered neurite outgrowth.

E4orf1: a novel ligand that improves glucose disposal in cell culture.

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Emily J Dhurandhar

Full Text Available Reducing dietary fat intake and excess adiposity, the cornerstones of behavioral treatment of insulin resistance (IR, are marginally successful over the long term. Ad36, a human adenovirus, offers a template to improve IR, independent of dietary fat intake or adiposity. Ad36 increases cellular glucose uptake via a Ras-mediated activation of phosphatidyl inositol 3-kinase(PI3K, and improves hyperglycemia in mice, despite a high-fat diet and without reducing adiposity. Ex-vivo studies suggest that Ad36 improves hyperglycemia in mice by increasing glucose uptake by adipose tissue and skeletal muscle, and by reducing hepatic glucose output. It is impractical to use Ad36 for therapeutic action. Instead, we investigated if the E4orf1 protein of Ad36, mediates its anti-hyperglycemic action. Such a candidate protein may offer an attractive template for therapeutic development. Experiment-1 determined that Ad36 'requires' E4orf1 protein to up-regulate cellular glucose uptake. Ad36 significantly increased glucose uptake in 3T3-L1 preadipocytes, which was abrogated by knocking down E4orf1 with siRNA. Experiment-2 identified E4orf1 as 'sufficient' to up-regulate glucose uptake. 3T3-L1 cells that inducibly express E4orf1, increased glucose uptake in an induction-dependent manner, compared to null vector control cells. E4orf1 up-regulated PI3K pathway and increased abundance of Ras--the obligatory molecule in Ad36-induced glucose uptake. Experiment-3: Signaling studies of cells transiently transfected with E4orf1 or a null vector, revealed that E4orf1 may activate Ras/PI3K pathway by binding to Drosophila discs-large (Dlg1 protein. E4orf1 activated total Ras and, particularly the H-Ras isoform. By mutating the PDZ domain binding motif (PBM of E4orf1, Experiment-4 showed that E4orf1 requires its PBM to increase Ras activation or glucose uptake. Experiment-5: In-vitro, a transient transfection by E4orf1 significantly increased glucose uptake in preadipocytes

E4orf1: a novel ligand that improves glucose disposal in cell culture.

Science.gov (United States)

Dhurandhar, Emily J; Dubuisson, Olga; Mashtalir, Nazar; Krishnapuram, Rashmi; Hegde, Vijay; Dhurandhar, Nikhil V

2011-01-01

Reducing dietary fat intake and excess adiposity, the cornerstones of behavioral treatment of insulin resistance (IR), are marginally successful over the long term. Ad36, a human adenovirus, offers a template to improve IR, independent of dietary fat intake or adiposity. Ad36 increases cellular glucose uptake via a Ras-mediated activation of phosphatidyl inositol 3-kinase(PI3K), and improves hyperglycemia in mice, despite a high-fat diet and without reducing adiposity. Ex-vivo studies suggest that Ad36 improves hyperglycemia in mice by increasing glucose uptake by adipose tissue and skeletal muscle, and by reducing hepatic glucose output. It is impractical to use Ad36 for therapeutic action. Instead, we investigated if the E4orf1 protein of Ad36, mediates its anti-hyperglycemic action. Such a candidate protein may offer an attractive template for therapeutic development. Experiment-1 determined that Ad36 'requires' E4orf1 protein to up-regulate cellular glucose uptake. Ad36 significantly increased glucose uptake in 3T3-L1 preadipocytes, which was abrogated by knocking down E4orf1 with siRNA. Experiment-2 identified E4orf1 as 'sufficient' to up-regulate glucose uptake. 3T3-L1 cells that inducibly express E4orf1, increased glucose uptake in an induction-dependent manner, compared to null vector control cells. E4orf1 up-regulated PI3K pathway and increased abundance of Ras--the obligatory molecule in Ad36-induced glucose uptake. Experiment-3: Signaling studies of cells transiently transfected with E4orf1 or a null vector, revealed that E4orf1 may activate Ras/PI3K pathway by binding to Drosophila discs-large (Dlg1) protein. E4orf1 activated total Ras and, particularly the H-Ras isoform. By mutating the PDZ domain binding motif (PBM) of E4orf1, Experiment-4 showed that E4orf1 requires its PBM to increase Ras activation or glucose uptake. Experiment-5: In-vitro, a transient transfection by E4orf1 significantly increased glucose uptake in preadipocytes, adipocytes, or

Biotransformation of (±)-4,8-dimethylcyclodeca-3(E),7(E)-dien-1β-ol and (+)-Hedycaryol by Cichorium intybus.

NARCIS (Netherlands)

Piet, Dennis P.; Minnaard, Adriaan J.; Heyden, Karel A. van der; Franssen, Maurice C.R.; Wijnberg, Joannes B.P.A.; Groot, Aede de

1995-01-01

The biotransformation of the synthetic (E,E)-1,5-cyclodecadienol 5 and (+)-hedycaryol (11) by a root suspension of fresh chicory has been investigated. Incubation of 5 with a root suspension gave a 2 : 1 mixture of the epimeric eudesmanediols 7a and 7b whereas 11 was selectively converted into

The Frequency of Cytochrome P450 2E1 Polymorphisms in Black South Africans

Directory of Open Access Journals (Sweden)

Paul K. Chelule

2006-01-01

Full Text Available Polymorphisms in the promoter region of the Cytochrome P4502E1 (CYP2E1 gene reportedly modify the metabolic activity of CYP2E1 enzyme, and have been associated with increased susceptibility to squamous cell carcinoma (SCC of the oesophagus in high prevalence areas such as China. To assess the frequency of these polymorphisms in Black South Africans, a population with a high incidence of oesophageal SCC, this study examined genomic DNA from 331 subjects for restriction fragment length polymorphisms in the CYP2E1 (RsaI and PstI digestion. The frequency of the CYP2E1 c1/c1 and c1/c3 genotypes was 95% and 5% respectively. The frequency of the CYP2E1 allele distribution was found to be markedly different between Chinese and South African populations; hence it is important to place racial differences into consideration when proposing allelic variants as genetic markers for cancer.

The eEF1A proteins: at the crossroads of oncogenesis, apoptosis and viral infections.

Directory of Open Access Journals (Sweden)

Georges eHerbein

2015-04-01

Full Text Available Eukaryotic translation elongation factors 1 alpha, eEF1A1 and eEF1A2, are not only translation factors, but also pleiotropic proteins that are highly expressed in human tumors, including breast cancer, ovarian cancer and lung cancer. eEF1A1 modulates cytoskeleton, exhibits chaperone-like activity and also controls cell proliferation and cell death. By contrast eEF1A2 protein favors oncogenesis as shown by the fact that overexpression of eEF1A2 leads to cellular transformation and gives rise to tumors in nude mice. The eEF1A2 protein stimulates the phospholipid signaling and activates the Akt-dependent cell migration and actin remodeling that ultimately favors tumorigenesis. By contrast, inactivation of eEF1A proteins leads to immunodeficiency, neural and muscular defects, and favors apoptosis. Finally, eEF1A proteins interact with several viral proteins resulting in enhanced viral replication, decreased apoptosis and increased cellular transformation. This review summarizes the recent findings on eEF1A proteins indicating that eEF1A proteins play a critical role in numerous human diseases through enhancement of oncogenesis, blockade of apoptosis and increased viral pathogenesis.

Fragment E1 labeled with I-123 in the detection of venous thrombosis

International Nuclear Information System (INIS)

Knight, L.C.; Maurer, A.H.; Robbins, P.S.; Malmud, L.S.; Budzynski, A.Z.

1985-01-01

Fragment E1, which has been shown to have specific binding affinity for thrombi in an animal model, was investigated in humans for its safety and ability to bind to venous thrombi. Human Fragment E1 was labeled with I-123 and administered intravenously to patients with proved or suspected deep vein thrombosis. The vascular distribution of radioactivity was documented by obtaining gamma camera images of the patients' legs for 30 minutes following administration of I-123-Fragment E1. All patients (n = 5) with documented venous thrombi had rapid localization of labeled Fragment E1 in the area of thrombus. Patients without evidence of thrombi (n = 5) showed no focal localization, although two of these patients showed diffuse uptake along the length of the veins, due to superficial phlebitis. Analysis of blood samples in four patients indicated that disappearance of Fragment E1 from the circulation was more rapid in individuals with thrombosis (t 1/2 = 20 min) than in individuals without thrombosis (t 1/2 = 90 min), and a radiolabeled species of high molecular weight was found in patients with thrombosis but was absent from patients without thrombosis. These early results suggest that radiolabeled Fragment E1 is a safe and potentially valuable agent for the rapid detection of venous thrombosis

Resposta de testes de hipersensibilidade tardia utilizando PPD e outros antígenos em crianças e adolescentes saudáveis e infectados pelo HIV-1 e vacinados com BCG

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Natalia Moriya Xavier da Costa

2011-10-01

Full Text Available INTRODUÇÃO: A contagem de células CD4+ representa marcador da resposta imune celular em pacientes infectados pelo HIV-1. Testes cutâneos de hipersensibilidade tardia (DTH podem ser empregados para avaliar in vivo respostas celulares a antígenos comuns. MÉTODOS: DTH para derivado proteico purificado de tuberculina (PPD, esporotriquina, tricofitina, candidina e estreptoquinase/estreptodornase foram realizados. Foram testados crianças/adolescentes infectados pelo HIV-1 (n=36 e indivíduos saudáveis (n=56, soronegativos para HIV-1/HIV-2 pareados por sexo-idade, todos com cicatriz vacinal por BCG. Teste exato de Fisher foi aplicado (p<0,05. RESULTADOS: Entre as crianças/adolescentes infectados pelo HIV-1, mediana de idade=8,1 anos; 20/36 eram do sexo masculino; 35 casos de transmissão vertical; 34 casos de AIDS sob terapia antirretroviral; mediana de carga viral = 3.04lc10 cópias/ml; mediana de contagem de células CD4+ = 701 células/μl. Entre os infectados e saudáveis a reatividade DTH a pelo menos um dos antígenos foi, respectivamente, 25% (9/36 e 87,5% (49/56 (p<0,001. Reatividade à candidina predominou nos infectados (8/36, 22% e ao PPD nos indivíduos saudáveis (40/56, 71,4%. A reatividade ao PPD entre infectados foi de 8,3% (p<0,01. A mediana da induração ao PPD foi 2,5mm (variação: 2-5mm entre infectados e 6,0mm (variação: 3-15mm entre os saudáveis. Não observamos correlação entre positividade ao PPD e idade. No grupo de infectados, não observamos correlação entre contagens de células CD4+ e reatividade ao DTH. CONCLUSÕES: Respostas DTH significativamente diminuídas, incluindo a reatividade ao PPD foram observadas em crianças/adolescentes infectados pelo HIV-1 comparadas com controles saudáveis, provavelmente refletindo doença avançada e supressão da imunidade mediada por células T.

EXPOSE-E: an ESA astrobiology mission 1.5 years in space.

Science.gov (United States)

Rabbow, Elke; Rettberg, Petra; Barczyk, Simon; Bohmeier, Maria; Parpart, André; Panitz, Corinna; Horneck, Gerda; von Heise-Rotenburg, Ralf; Hoppenbrouwers, Tom; Willnecker, Rainer; Baglioni, Pietro; Demets, René; Dettmann, Jan; Reitz, Guenther

2012-05-01

The multi-user facility EXPOSE-E was designed by the European Space Agency to enable astrobiology research in space (low-Earth orbit). On 7 February 2008, EXPOSE-E was carried to the International Space Station (ISS) on the European Technology Exposure Facility (EuTEF) platform in the cargo bay of Space Shuttle STS-122 Atlantis. The facility was installed at the starboard cone of the Columbus module by extravehicular activity, where it remained in space for 1.5 years. EXPOSE-E was returned to Earth with STS-128 Discovery on 12 September 2009 for subsequent sample analysis. EXPOSE-E provided accommodation in three exposure trays for a variety of astrobiological test samples that were exposed to selected space conditions: either to space vacuum, solar electromagnetic radiation at >110 nm and cosmic radiation (trays 1 and 3) or to simulated martian surface conditions (tray 2). Data on UV radiation, cosmic radiation, and temperature were measured every 10 s and downlinked by telemetry. A parallel mission ground reference (MGR) experiment was performed on ground with a parallel set of hardware and samples under simulated space conditions. EXPOSE-E performed a successful 1.5-year mission in space.

IPCC IS92 Emissions Scenarios (A, B, C, D, E, F) Dataset Version 1.1

Data.gov (United States)

National Aeronautics and Space Administration — The Intergovernmental Panel on Climate Change (IPCC) IS92 Emissions Scenarios (A, B, C, D, E, F) Dataset Version 1.1 consists of six global and regional greenhouse...

Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2.

Science.gov (United States)

Le Bacquer, Olivier; Petroulakis, Emmanuel; Paglialunga, Sabina; Poulin, Francis; Richard, Denis; Cianflone, Katherine; Sonenberg, Nahum

2007-02-01

The most common pathology associated with obesity is insulin resistance, which results in the onset of type 2 diabetes mellitus. Several studies have implicated the mammalian target of rapamycin (mTOR) signaling pathway in obesity. Eukaryotic translation initiation factor 4E-binding (eIF4E-binding) proteins (4E-BPs), which repress translation by binding to eIF4E, are downstream effectors of mTOR. We report that the combined disruption of 4E-BP1 and 4E-BP2 in mice increased their sensitivity to diet-induced obesity. Increased adiposity was explained at least in part by accelerated adipogenesis driven by increased expression of CCAAT/enhancer-binding protein delta (C/EBPdelta), C/EBPalpha, and PPARgamma coupled with reduced energy expenditure, reduced lipolysis, and greater fatty acid reesterification in the adipose tissue of 4E-BP1 and 4E-BP2 double KO mice. Increased insulin resistance in 4E-BP1 and 4E-BP2 double KO mice was associated with increased ribosomal protein S6 kinase (S6K) activity and impairment of Akt signaling in muscle, liver, and adipose tissue. These data clearly demonstrate the role of 4E-BPs as a metabolic brake in the development of obesity and reinforce the idea that deregulated mTOR signaling is associated with the development of the metabolic syndrome.

Prototyping the E-ELT M1 local control system communication infrastructure

Science.gov (United States)

Argomedo, J.; Kornweibel, N.; Grudzien, T.; Dimmler, M.; Andolfato, L.; Barriga, P.

2016-08-01

The primary mirror of the E-ELT is composed of 798 hexagonal segments of about 1.45 meters across. Each segment can be moved in piston and tip-tilt using three position actuators. Inductive edge sensors are used to provide feedback for global reconstruction of the mirror shape. The E-ELT M1 Local Control System will provide a deterministic infrastructure for collecting edge sensor and actuators readings and distribute the new position actuators references while at the same time providing failure detection, isolation and notification, synchronization, monitoring and configuration management. The present paper describes the prototyping activities carried out to verify the feasibility of the E-ELT M1 local control system communication architecture design and assess its performance and potential limitations.

Differences in E-Cadherin and Syndecan-1 Expression in Different Types of Ameloblastomas

Science.gov (United States)

López-Verdín, Sandra; Pereira-Prado, Vanesa

2018-01-01

Ameloblastomas are a group of benign, locally aggressive, recurrent tumors characterized by their slow and infiltrative growth. E-Cadherin and syndecan-1 are cell adhesion molecules related to the behavior of various tumors, including ameloblastomas. Ninety-nine ameloblastoma samples were studied; the expression of E-cadherin and syndecan-1 were evaluated by immunohistochemistry. E-Cadherin and epithelial syndecan-1 were more highly expressed in intraluminal/luminal unicystic ameloblastoma than in mural unicystic ameloblastoma and solid/multicystic ameloblastoma, whereas the stromal expression of syndecan-1 was higher in mural unicystic ameloblastoma and solid/multicystic ameloblastoma. Synchronicity was observed between E-cadherin and epithelial syndecan-1; the expression was correlated with intensity in all cases. There was a strong association between expression and tumor size and recurrence. The evaluation of the expression of E-cadherin and syndecan-1 are important for determining the potential aggressiveness of ameloblastoma variants. Future studies are required to understand how the expression of these markers is related to tumor aggressiveness.

Calcein represses human papillomavirus 16 E1-E2 mediated DNA replication via blocking their binding to the viral origin of replication.

Science.gov (United States)

Das, Dipon; Smith, Nathan W; Wang, Xu; Richardson, Stacie L; Hartman, Matthew C T; Morgan, Iain M

2017-08-01

Human papillomaviruses are causative agents in several human diseases ranging from genital warts to ano-genital and oropharyngeal cancers. Currently only symptoms of HPV induced disease are treated; there are no antivirals available that directly target the viral life cycle. Previously, we determined that the cellular protein TopBP1 interacts with the HPV16 replication/transcription factor E2. This E2-TopBP1 interaction is essential for optimal E1-E2 DNA replication and for the viral life cycle. The drug calcein disrupts the interaction of TopBP1 with itself and other host proteins to promote cell death. Here we demonstrate that calcein blocks HPV16 E1-E2 DNA replication via blocking the viral replication complex forming at the origin of replication. This occurs at non-toxic levels of calcein and demonstrates specificity as it does not block the ability of E2 to regulate transcription. We propose that calcein or derivatives could be developed as an anti-HPV therapeutic. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-term trends in the ionospheric E and F1 regions

Directory of Open Access Journals (Sweden)

J. Bremer

2008-05-01

Full Text Available Ground based ionosonde measurements are the most essential source of information about long-term variations in the ionospheric E and F1 regions. Data of such observations have been derived at many different ionospheric stations all over the world some for more than 50 years. The standard parameters foE, h'E, and foF1 are used for trend analyses in this paper. Two main problems have to be considered in these analyses. Firstly, the data series have to be homogeneous, i.e. the observations should not be disturbed by artificial steps due to technical reasons or changes in the evaluation algorithm. Secondly, the strong solar and geomagnetic influences upon the ionospheric data have carefully to be removed by an appropriate regression analysis. Otherwise the small trends in the different ionospheric parameters cannot be detected.

The trends derived at individual stations differ markedly, however their dependence on geographic or geomagnetic latitude is only small. Nevertheless, the mean global trends estimated from the trends at the different stations show some general behaviour (positive trends in foE and foF1, negative trend in h'E which can at least qualitatively be explained by an increasing atmospheric greenhouse effect (increase of CO₂ content and other greenhouse gases and decreasing ozone values. The positive foE trend is also in qualitative agreement with rocket mass spectrometer observations of ion densities in the E region. First indications could be found that the changing ozone trend at mid-latitudes (before about 1979, between 1979 until 1995, and after about 1995 modifies the estimated mean foE trend.

Induction of mesenchymal cell phenotypes in lung epithelial cells by adenovirus E1A.

Science.gov (United States)

Behzad, A R; Morimoto, K; Gosselink, J; Green, J; Hogg, J C; Hayashi, S

2006-12-01

Epithelial-mesenchymal transformation is now recognised as an important feature of tissue remodelling. The present report concerns the role of adenovirus infection in inducing this transformation in an animal model of chronic obstructive pulmonary disease. Guinea pig primary peripheral lung epithelial cells (PLECs) transfected with adenovirus E1A (E1A-PLECs) were compared to guinea pig normal lung fibroblasts (NLFs) transfected with E1A (E1A-NLFs). These cells were characterised by PCR, immunocytochemistry, electron microscopy, and Western and Northern blot analyses. Electrophoretic mobility shift assays were performed in order to examine nuclear factor (NF)-kappaB and activator protein (AP)-1 binding activities. E1A-PLECs and E1A-NLFs positive for E1A DNA, mRNA and protein expressed cytokeratin and vimentin but not smooth muscle alpha-actin. Both exhibited cuboidal morphology and junctional complexes, but did not contain lamellar bodies or express surfactant protein A, B or C mRNAs. These two cell types differed, however, in their NF-kappaB and AP-1 binding after lipopolysaccharide stimulation, possibly due to differences in the expression of the subunits that comprise these transcriptional complexes. E1A transfection results in the transformation of peripheral lung epithelial cells and normal lung fibroblasts to a phenotype intermediate between that of the two primary cells. It is postulated that this intermediate phenotype may play a major role in the remodelling of the airways in chronic obstructive pulmonary disease associated with persistence of adenovirus E1A DNA.

Mitotic protein kinase CDK1 phosphorylation of mRNA translation regulator 4E-BP1 Ser83 may contribute to cell transformation

Energy Technology Data Exchange (ETDEWEB)

Velasquez, Celestino; Cheng, Erdong; Shuda, Masahiro; Lee-Oesterreich, Paula J.; Pogge von Strandmann, Lisa; Gritsenko, Marina A.; Jacobs, Jon M.; Moore, Patrick S.; Chang, Yuan

2016-07-11

mTOR-directed 4E-BP1 phosphorylation promotes cap-dependent translation and tumorigen-esis. During mitosis, CDK1 substitutes for mTOR and fully phosphorylates 4E-BP1 at canoni-cal as well a non-canonical S83 site resulting in a mitosis-specific hyperphosphorylated δ isoform. Colocalization studies with a phospho-S83 specific antibody indicate that 4E-BP1 S83 phosphorylation accumulates at centrosomes during prophase, peaks at metaphase, and decreases through telophase. While S83 phosphorylation of 4E-BP1 does not affect in vitro cap-dependent translation, nor eIF4G/4E-BP1 cap-binding, expression of an alanine substitution mutant 4E-BP1.S83A partially reverses rodent cell transformation induced by Merkel cell polyomavirus (MCV) small T (sT) antigen viral oncoprotein. In contrast to inhibitory mTOR 4E-BP1 phosphorylation, these findings suggest that mitotic CDK1-directed phosphorylation of δ-4E-BP1 may yield a gain-of-function, distinct from translation regulation, that may be important in tumorigenesis and mitotic centrosome function.

Endothelin-1 overexpression exacerbates atherosclerosis and induces aortic aneurysms in apolipoprotein E knockout mice.

Science.gov (United States)

Li, Melissa W; Mian, Muhammad Oneeb Rehman; Barhoumi, Tlili; Rehman, Asia; Mann, Koren; Paradis, Pierre; Schiffrin, Ernesto L

2013-10-01

Endothelin (ET)-1 plays a role in vascular reactive oxygen species production and inflammation. ET-1 has been implicated in human atherosclerosis and abdominal aortic aneurysm (AAA) development. ET-1 overexpression exacerbates high-fat diet-induced atherosclerosis in apolipoprotein E(-/-) (Apoe(-/-)) mice. ET-1-induced reactive oxygen species and inflammation may contribute to atherosclerosis progression and AAA development. Eight-week-old male wild-type mice, transgenic mice overexpressing ET-1 selectively in endothelium (eET-1), Apoe(-/-) mice, and eET-1/Apoe(-/-) mice were fed high-fat diet for 8 weeks. eET-1/Apoe(-/-) had a 45% reduction in plasma high-density lipoprotein (P<0.05) and presented ≥ 2-fold more aortic atherosclerotic lesions compared with Apoe(-/-) (P<0.01). AAAs were detected only in eET-1/Apoe(-/-) (8/21; P<0.05). Reactive oxygen species production was increased ≥ 2-fold in perivascular fat, media, or atherosclerotic lesions in the ascending aorta and AAAs of eET-1/Apoe(-/-) compared with Apoe(-/-) (P<0.05). Monocyte/macrophage infiltration was enhanced ≥ 2.5-fold in perivascular fat of ascending aorta and AAAs in eET-1/Apoe(-/-) compared with Apoe(-/-) (P<0.05). CD4(+) T cells were detected almost exclusively in perivascular fat (3/6) and atherosclerotic lesions (5/6) in ascending aorta of eET-1/Apoe(-/-) (P<0.05). The percentage of spleen proinflammatory Ly-6C(hi) monocytes was enhanced 26% by ET-1 overexpression in Apoe(-/-) (P<0.05), and matrix metalloproteinase-2 was increased 2-fold in plaques of eET-1/Apoe(-/-) (P<0.05) compared with Apoe(-/-). ET-1 plays a role in progression of atherosclerosis and AAA formation by decreasing high-density lipoprotein, and increasing oxidative stress, inflammatory cell infiltration, and matrix metalloproteinase-2 in perivascular fat, vascular wall, and atherosclerotic lesions.

Repair of ultraviolet-light damaged ColE1 factor carrying Escherichia coli genes for guanine synthesis

International Nuclear Information System (INIS)

Kibe, A.; Shimada, K.; Tagaki, Y.

1979-01-01

Hybrid ColE1 plasmids called ColE1-cos lambda-guaA or ColE1-cos lambda-gal can be efficiently transduced into various E.coli K-12 cells through packaging into lambda phage particles. Using these plasmids, repair of ultraviolet-light (UV) damaged ColE1 DNAs was studied in various UV sensitive E.coli K-12 mutants. The host mutations uvrA and uvrB markedly reduced host-cell reactivation of UV-irradiated ColE1-cos lambda-guaA. Pre-existing hybrid ColE1 plasmids had no effect on the frequency of lambda phage-mediated transduction of another differentially marked hybrid ColE1 DNAs. ColE1-cos lambda-guaA and ColE1-cos lambda-gal DNAs could temporarily but not stably co-exist in E.coli K-12 recA cells. The presence of ColE1-cos lambda-gal in uvrB cells promoted the repair of super-infected UV-irradiated ColE1-cos lambda-guaA about 7-fold. The same ColE1-cos lambda-gal plasmid in a uvrB recA double mutant did not have this promoting effect. These results indicate that the effect of resident hybrid ColE1 plasmids is manifested by the host recA + gene function(s) and suggest that ColE1 plasmit itself provides no recA + -like functions. (orig.) [de

Repair of ultraviolet-light damaged ColE1 factor carrying Escherichia coli genes for guanine synthesis

Energy Technology Data Exchange (ETDEWEB)

Kibe, A; Shimada, K; Tagaki, Y [Kyushu Univ., Fukuoka (Japan). Dept. of Biochemistry

1979-01-01

Hybrid ColE1 plasmids called ColE1-cos lambda-guaA or ColE1-cos lambda-gal can be efficiently transduced into various E.coli K-12 cells through packaging into lambda phage particles. Using these plasmids, repair of ultraviolet-light (UV) damaged ColE1 DNAs was studied in various UV sensitive E.coli K-12 mutants. The host mutations uvrA and uvrB markedly reduced host-cell reactivation of UV-irradiated ColE1-cos lambda-guaA. Pre-existing hybrid ColE1 plasmids had no effect on the frequency of lambda phage-mediated transduction of another differentially marked hybrid ColE1 DNAs. ColE1-cos lambda-guaA and ColE1-cos lambda-gal DNAs could temporarily but not stably co-exist in E.coli K-12 recA cells. The presence of ColE1-cos lambda-gal in uvrB cells promoted the repair of super-infected UV-irradiated ColE1-cos lambda-guaA about 7-fold. The same ColE1-cos lambda-gal plasmid in a uvrB recA double mutant did not have this promoting effect. These results indicate that the effect of resident hybrid ColE1 plasmids is manifested by the host recA/sup +/ gene function(s) and suggest that ColE1 plasmit itself provides no recA/sup +/-like functions.

(E-1-(2-Aminophenyl-3-(4-chlorophenylprop-2-en-1-one

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Rodrigo Abonia

2016-10-01

Full Text Available The title chalcone (E-1-(2-aminophenyl-3-(4-chlorophenylprop-2-en-1-one was prepared with an excellent yield from a Claisen–Schmidt condensation reaction between o-aminoacetophenone and p-chlorobenzaldehyde. This product will be used as a key precursor for the development of an alternative route for the total synthesis of dubamine and graveoline alkaloids. Single crystals of the title compound suitable for X-ray diffraction were grown via slow evaporation in ethanol at room temperature. A complete crystallographic study was performed in depth to unequivocally confirm its structure and determine some interesting supramolecular properties. The crystal structure of the title o-aminochalcone, C15H12ClNO, shows two molecules per asymmetric unit (Z′ = 2 and adopts an E configuration about the C=C double bond. In the title compound, the mean plane of the non-H atoms of the central chalcone fragment C—C(O—C—C—C is as follows: [r.m.s. deviation = 0.0130 Å for A-B and 0.0043 for C-D molecules]. In the crystal, molecules are linked by N—H...N and C—H...O, hydrogen bonds forming edge-fused R66(46 rings parallel to (100. Additionally, N—H...O hydrogen bonds generate a three-dimensional network.

Tetraaquatetrakis{μ3-3,3′-[(E,E-ethane-1,2-diylbis(nitrilomethylidyne]benzene-1,2-diolato}octazinc(II N,N-dimethylformamide hexasolvate

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Lan-Sun Zheng

2009-12-01

Full Text Available The asymmetric unit of the title compound [Zn8(C16H12N2O44(H2O4]·6C3H7NO, consists of eight ZnII cations, four tetravalent anionic ligands, L4− (L4− = 3,3′-(1E,1′E-(ethane-1,2-diylbis(azan-1-yl-1-ylidenebis(methan-1-yl-1-ylidenedibenzene-1,2-bis(olate, four coordinated water molecules and six N,N-dimethylformamide solvate molecules. The coordination complex comprises an octanuclear ZnII unit with its ZnII centers coordinated in two discrete distorted square-pyramidal geometries. Four ZnII atoms each coordinate to two nitrogen atoms and two phenolate oxygen atoms from an individual L4− ligand and one coordinated water molecule. The other four ZnII atoms each bind to five phenolate oxygen atoms from three different L4− ligands. In the crystal structure, the ZnII complex unit, coordinated water molecules and dimethylformamide solvate molecules are linked via O—H...O and C—H...O hydrogen bonds. Molecules are connected by additional intermolecular O—H...O and C—H...O hydrogen bonds, forming an extensive three dimensional framework.

Overexpression of Myo1e in mouse podocytes enhances cellular endocytosis, migration, and adhesion.

Science.gov (United States)

Jin, Xia; Wang, Wenjing; Mao, Jianhua; Shen, Huijun; Fu, Haidong; Wang, Xia; Gu, Weizhong; Liu, Aimin; Yu, Huimin; Shu, Qiang; Du, Lizhong

2014-02-01

Podocytes are a terminally differentiated and highly specialized cell type in the glomerulus that forms a crucial component of the glomerular filtration barrier. Recently, Myo1e was identified in the podocytes of glomeruli. Myo1e podocyte-specific knockout mice exhibit proteinuria, podocyte foot process effacement, glomerular basement membrane disorganization, signs of chronic renal injury, and kidney inflammation. After overexpression of Myo1e in a conditionally immortalized mouse podocyte cell line (MPC5), podocyte migration was evaluated via transwell assay, endocytosis was evaluated using FITC-transferrin, and adhesion was evaluated using a detachment assay after puromycin aminonucleoside treatment. Myo1e overexpression significantly increased the adherence of podocytes. ANOVA analysis indicated significant differences for cell adhesion between the overexpression and control groups (overexpression vs. control, t = 11.3199, P = 0.005; overexpression vs. negative control, t = 12.0570, P = 0.0006). Overexpression of Myo1e inhibited puromycin aminonucleoside-induced podocyte detachment, and the number of cells remaining on the bottom of the culture plate increased. Cell migration was enhanced in Myo1e-overexpressing podocytes in the transwell migration assay. Internalization of FITC-transferrin also increased in Myo1e-overexpressing podocytes relative to control cells. Overexpression of Myo1e can enhance podocyte migration ability, endocytosis, and attachment to the glomerular basement membrane. Restoration of Myo1e expression in podocytes may therefore strengthen their functional integrity against environmental and mechanical injury. © 2013 Wiley Periodicals, Inc.

User requirements Massive Point Clouds for eSciences (WP1)

NARCIS (Netherlands)

Suijker, P.M.; Alkemade, I.; Kodde, M.P.; Nonhebel, A.E.

2014-01-01

This report is a milestone in work package 1 (WP1) of the project Massive point clouds for eSciences. In WP1 the basic functionalities needed for a new Point Cloud Spatial Database Management System are identified. This is achieved by (1) literature research, (2) discussions with the project

Methodology to assay CYP2E1 mixed function oxidase catalytic activity and its induction

Directory of Open Access Journals (Sweden)

Arthur I. Cederbaum

2014-01-01

Full Text Available The cytochrome P450 mixed function oxidase enzymes are the major catalysts involved in drug metabolism. There are many forms of P450. CYP2E1 metabolizes many toxicologically important compounds including ethanol and is active in generating reactive oxygen species. Since several of the contributions in the common theme series “Role of CYP2E1 and Oxidative/Nitrosative Stress in the Hepatotoxic Actions of Alcohol” discuss CYP2E1, this methodology review describes assays on how CYP2E1 catalytic activity and its induction by ethanol and other inducers can be measured using substrate probes such as the oxidation of para-nitrophenol to para-nitrocatechol and the oxidation of ethanol to acetaldehyde. Approaches to validate that a particular reaction e.g. oxidation of a drug or toxin is catalyzed by CYP2E1 or that induction of that reaction is due to induction of CYP2E1 are important and specific examples using inhibitors of CYP2E1, anti-CYP2E1 IgG or CYP2E1 knockout and knockin mice will be discussed.

Effect of resveratrol on 17beta-estradiol sulfation by human hepatic and jejunal S9 and recombinant sulfotransferase 1E1.

Science.gov (United States)

Furimsky, Anna M; Green, Carol E; Sharp, Lewanne E Hunt; Catz, Paul; Adjei, Araba A; Parman, Toufan; Kapetanovic, Izet M; Weinshilboum, Richard M; Iyer, Lalitha V

2008-01-01

The purpose of this study was to investigate the sulfation of resveratrol (3,5,4'-trihydroxystilbene) and its potential to exhibit drug-drug interactions via sulfation. The possible interaction of resveratrol with 17beta-estradiol (E2), a major estrogen hormone and prototypic substrate for sulfate conjugation, was studied. Resveratrol and E2 are both known to undergo sulfate conjugation catalyzed by human sulfotransferases (SULTs). Resveratrol is a phytoestrogen with mixed estrogen agonist/antagonist properties that is being developed as a chemopreventive agent. The sulfate conjugation of E2 and resveratrol were studied individually using S9 fractions from human liver and jejunum as well as recombinant human SULT isoforms. The sulfation of E2 (3-20 nM) was then investigated in the presence of various concentrations (0, 0.5, 1, and 2 microM) of resveratrol using the two S9 preparations as well as recombinant SULT1E1, the major isoform responsible for E2 sulfation. Resveratrol inhibited E2 sulfation with estimated K(i) values of 1.1 microM (liver), 0.6 microM (jejunum), and 2.3 microM (SULT1E1), concentrations that could be pharmacologically relevant. The results suggest that these phytoestrogens can potentially alter the homeostasis of estrogen levels. These findings also imply that resveratrol may inhibit the metabolism of other estrogen analogs or therapeutic agents such as ethinylestradiol or dietary components that are also substrates for SULT1E1.

Anik-E1 and E2 satellite failures of January 1994 revisited

Science.gov (United States)

Lam, H.-L.; Boteler, D. H.; Burlton, B.; Evans, J.

2012-10-01

The consecutive failures of the geosynchronous Anik-E1 communication satellite on January 20, 1994, and Anik-E2 about nine hours later on January 21 (both incidents occurred on January 20 local time) received considerable publicity because the malfunctions of the satellites disrupted television and computer data transmissions across Canada, as well as telephone services to remote northern communities for hours. This often-cited event is revisited here with materials not covered before. Using publicly available information, Anik-E failure details, media coverage, recovery effort and cost incurred are first presented. This is then followed by scrutiny of space weather conditions pertinent to the occurrences of the Anik-E upsets. We trace the space weather episode's inception on the Sun, propagation through interplanetary medium, and manifestation in magnetic field variations as well as in energetic electron flux increases, and its eventual impact on the Anik-Es. The genesis of the energetic electron enhancements that have been blamed for the satellite malfunctions is thus traceable via high-speed solar wind stream with Alfven wave fluctuations to a longitudinally wide coronal hole on the Sun. Furthermore, strong magnetic pulsations preceding electron flux peaks indicate Pc5 ULF (Ultra Low Frequency) waves as a probable acceleration mechanism for the energetic electron flux enhancement that resulted in the internal charging of the Anik-Es. The magnetic fluctuations may even be possible triggers for the subsequent discharge that caused the satellites to malfunction. This incident illustrates that satellite operators should be on alert for elevated high-energy electron environment that is above established thresholds, as specifications in satellite design may not render a satellite immune from internal charging.

Expression of tung tree diacylglycerol acyltransferase 1 in E. coli

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Klasson K Thomas

2011-07-01

Full Text Available Abstract Background Diacylglycerol acyltransferases (DGATs catalyze the final and rate-limiting step of triacylglycerol (TAG biosynthesis in eukaryotic organisms. Database search has identified at least 59 DGAT1 sequences from 48 organisms, but the expression of any DGAT1 as a full-length protein in E. coli had not been reported because DGAT1s are integral membrane proteins and difficult to express and purify. The objective of this study was to establish a procedure for expressing full-length DGAT1 in E. coli. Results An expression plasmid containing the open reading frame for tung tree (Vernicia fordii DGAT1 fused to maltose binding protein and poly-histidine affinity tags was constructed and expressed in E. coli BL21(DE3. Immunoblotting showed that the recombinant DGAT1 (rDGAT1 was expressed, but mostly targeted to the membranes and insoluble fractions. Extensive degradation also occurred. Nonetheless, the fusion protein was partially purified from the soluble fraction by Ni-NTA and amylose resin affinity chromatography. Multiple proteins co-purified with DGAT1 fusion protein. These fractions appeared yellow in color and contained fatty acids. The rDGAT1 was solubilized from the insoluble fraction by seven detergents and urea, with SDS and Triton X-100 being the most effective detergents. The solubilized rDGAT1 was partially purified by Ni-NTA affinity chromatography. PreScission protease digestion confirmed the identity of rDGAT1 and showed extensive precipitation following Ni-NTA affinity purification. Conclusions This study reports the first procedure for expressing full-length DGAT1 from any species using a bacterial expression system. The results suggest that recombinant DGAT1 is degraded extensively from the carboxyl terminus and associated with other proteins, lipids, and membranes.

Therapeutic Strategies Against Cyclin E1 Amplified Ovarian Cancers

Science.gov (United States)

2017-10-01

13-14 ( References ) 1. INTRODUCTION: Approximately 20% of high grade serous ovarian cancers harbor Cyclin E1 (CCNE1) amplification and are associated... Harvard Medical School and was named Director of Translational Research in the Gynecologic Oncology Program at Dana-Farber Cancer Institute. How...on HDAC6 activity. Nat Cell Biol 19:962-973. PMID: 28737768. PMC5541905. Books or other non-periodical, one-time publications. “Nothing to Report

E2F-1 induces melanoma cell apoptosis via PUMA up-regulation and Bax translocation

International Nuclear Information System (INIS)

Hao, Hongying; Dong, Yanbin; Bowling, Maria T; Gomez-Gutierrez, Jorge G; Zhou, H Sam; McMasters, Kelly M

2007-01-01

PUMA is a pro-apoptotic Bcl-2 family member that has been shown to be involved in apoptosis in many cell types. We sought to ascertain whether induction of PUMA plays a crucial role in E2F-1-induced apoptosis in melanoma cells. PUMA gene and protein expression levels were detected by real-time PCR and Western blot in SK-MEL-2 and HCT116 cell lines after Ad-E2F-1 infection. Activation of the PUMA promoter by E2F-1 overexpression was detected by dual luciferase reporter assay. E2F-1-induced Bax translocation was shown by immunocytochemistry. The induction of caspase-9 activity was measured by caspase-9 colorimetric assay kit. Up-regulation of the PUMA gene and protein by E2F-1 overexpression was detected by real-time PCR and Western blot analysis in the SK-MEL-2 melanoma cell line. In support of this finding, we found six putative E2F-1 binding sites within the PUMA promoter. Subsequent dual luciferase reporter assay showed that E2F-1 expression could increase the PUMA gene promoter activity 9.3 fold in SK-MEL-2 cells. The role of PUMA in E2F-1-induced apoptosis was further investigated in a PUMA knockout cell line. Cell viability assay showed that the HCT116 PUMA-/- cell line was more resistant to Ad-E2F-1-mediated cell death than the HCT116 PUMA+/+ cell line. Moreover, a 2.2-fold induction of the PUMA promoter was also noted in the HCT116 PUMA+/+ colon cancer cell line after Ad-E2F-1 infection. Overexpression of a truncated E2F-1 protein that lacks the transactivation domain failed to up-regulate PUMA promoter, suggesting that PUMA may be a transcriptional target of E2F-1. E2F-1-induced cancer cell apoptosis was accompanied by Bax translocation from the cytosol to mitochondria and the induction of caspase-9 activity, suggesting that E2F-1-induced apoptosis is mediated by PUMA through the cytochrome C/Apaf-1-dependent pathway. Our studies strongly demonstrated that E2F-1 induces melanoma cell apoptosis via PUMA up-regulation and Bax translocation. The signaling

Synthesis of 6-Substituted 2-Pyrones Starting from Renewable Resources: Total Synthesis of Sibirinone, (E)-6-(Pent-1-en-1-yl)-2H-pyran-2-one, and (E)-6-(Hept-1-en-1-yl)-2H-pyran-2-one.

Science.gov (United States)

Dobler, Daniel; Reiser, Oliver

2016-11-04

An atom-economic reaction sequence to 6-substituted 2-pyrones was developed starting from furfuryl alcohol, a renewable resource made from bran or bagasse, and aldehydes, utilizing a thermal rearrangement of cyclopentadienone epoxides as key step. Derivatives bearing a hydroxyalkyl side chain could be enzymatically resolved, providing access to enantiomerically pure 2-pyrones, or converted to alkenyl-substituted 2-pyrones such as naturally occurring sibirinone, (E)-6-(pent-1-en-1-yl)-2H-pyran-2-one, and (E)-6-(hept-1-en-1-yl)-2H-pyran-2-one.

Rigorous Photogrammetric Processing of CHANG'E-1 and CHANG'E-2 Stereo Imagery for Lunar Topographic Mapping

Science.gov (United States)

Di, K.; Liu, Y.; Liu, B.; Peng, M.

2012-07-01

Chang'E-1(CE-1) and Chang'E-2(CE-2) are the two lunar orbiters of China's lunar exploration program. Topographic mapping using CE-1 and CE-2 images is of great importance for scientific research as well as for preparation of landing and surface operation of Chang'E-3 lunar rover. In this research, we developed rigorous sensor models of CE-1 and CE-2 CCD cameras based on push-broom imaging principle with interior and exterior orientation parameters. Based on the rigorous sensor model, the 3D coordinate of a ground point in lunar body-fixed (LBF) coordinate system can be calculated by space intersection from the image coordinates of con-jugate points in stereo images, and the image coordinates can be calculated from 3D coordinates by back-projection. Due to uncer-tainties of the orbit and the camera, the back-projected image points are different from the measured points. In order to reduce these inconsistencies and improve precision, we proposed two methods to refine the rigorous sensor model: 1) refining EOPs by correcting the attitude angle bias, 2) refining the interior orientation model by calibration of the relative position of the two linear CCD arrays. Experimental results show that the mean back-projection residuals of CE-1 images are reduced to better than 1/100 pixel by method 1 and the mean back-projection residuals of CE-2 images are reduced from over 20 pixels to 0.02 pixel by method 2. Consequently, high precision DEM (Digital Elevation Model) and DOM (Digital Ortho Map) are automatically generated.

Photon radiation in e{sup +}e{sup -}→hadrons at low energies with carlomat3.1

Energy Technology Data Exchange (ETDEWEB)

Jegerlehner, Fred [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Humboldt-Universitaet, Berlin (Germany). Inst. fuer Physik; Kolodziej, Karol [Univ. of Silesia, Katowice (Poland). Inst. of Physics

2017-04-25

We present a sample of results for the cross sections of several processes of low energetic e{sup +}e{sup -} annihilation into final states containing pions accompanied by one or two photons, or a light lepton pair. The results, which have been obtained with a new version of a multipurpose Monte Carlo program carlomat, labelled 3.1, demonstrate new capabilities of the program which, among others, include a possibility of taking into account either the initial or final state radiation separately, or both at a time, and a possibility of inclusion of the electromagnetic charged pion form factor for processes with charged pion pairs. We also discuss some problems related to the U(1) electromagnetic gauge invariance.

Photon radiation in e{sup +}e{sup -} → hadrons at low energies with carlomat3.1

Energy Technology Data Exchange (ETDEWEB)

Jegerlehner, Fred [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Institut fuer Physik, Humboldt-Universitaet zu Berlin, Berlin (Germany); Kolodziej, Karol [Institute of Physics, University of Silesia, Katowice (Poland)

2017-04-15

We present a sample of results for the cross sections of several processes of low energetic e{sup +}e{sup -} annihilation into final states containing pions accompanied by one or two photons, or a light lepton pair. The results, which have been obtained with a new version of a multipurpose Monte Carlo program carlomat, labelled 3.1, demonstrate new capabilities of the program which, among others, include a possibility of taking into account either the initial or final state radiation separately, or both at a time, and a possibility of inclusion of the electromagnetic charged pion form factor for processes with charged pion pairs. We also discuss some problems related to the U(1) electromagnetic gauge invariance. (orig.)

Expressão dos genes que codificam as proteínas anexina-1 e galectina-1 nos pólipos rinossinusais e sua modulação pelo glicocorticoide

OpenAIRE

Fernandes,Atílio Maximino; Babeto,Erica; Rahal,Paula; Provazzi,Paola Jocelan Scarin; Hidalgo,Claudia Augusta; Anselmo-Lima,Wilma T

2010-01-01

A fisiopatologia da polipose rinossinusal não é totalmente compreendida, apesar de várias hipóteses em relação ao seu processo inflamatório. OBJETIVOS: Estudo prospectivo da expressão dos genes das proteínas, anexina-1 e a galectina-1, que têm ação anti-inflamatória, e sua modulação pelo glicocorticoide. MATERIAL E MÉTODOS: Onze pacientes portadores de polipose rinossinusal tiveram biopsiados seus pólipos em dois momentos: na ausência de glicocorticoide sistêmico, e na sua presença. Nas duas ...

Monoclonal antibodies directed to E1 glycoprotein of rubella virus

International Nuclear Information System (INIS)

Umino, Y.; Sato, A.; Katow, S.; Matsuno, T.; Sugiura, A.

1985-01-01

We have prepared four monoclonal antibodies to rubella virus E1 glycoprotein. Three nonoverlapping antigenic sites were delineated on E1 protein by competitive binding assays. Antibodies binding to one site were characterized by high hemagglutination inhibition (HI) titer but poor neutralizing activity. The addition of antiglobulin conferred neutralizing activity. Antibodies directed to two other antigenic sites had modest hemolysis inhibition but little or no HI and neutralizing activities. The addition of antiglobulin markedly augmented HI activity but had little effect on neutralizing activity. Epitopes defined by three antibodies were conserved among four rubella virus strains examined. (Author)

(E-3-(4-Bromophenyl-1-(3,4-dichlorophenylprop-2-en-1-one

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Rajni Kant

2009-04-01

Full Text Available The molecule of the title compound, C15H9BrCl2O, is shown to be the E isomer, with the 3,4-dichlorobenzoyl and p-bromophenyl substituents in trans positions with respect to the chalcone olefin bond. The molecule is non-planar, the two aromatic rings forming a dihedral angle of 49.58 (1°.

Expression of CYP2E1 in human nasopharynx and its metabolic effect in vitro.

Science.gov (United States)

Hou, De-Fu; Wang, Shui-Liang; He, Zhi-Min; Yang, Fang; Chen, Zhu-Chu

2007-04-01

It was evident that nitrosamines can act directly on target tissue and result in carcinogenesis. As has been shown, the carcinogenic activity of nitrosamines relied on its bioactivation by Cytochrome P450 2E1 (CYP2E1). In this study, we investigated the expression of CYP2E1 in Nasopharyngeal carcinoma (NPC) cells, embryonic nasopharyngeal epithelial tissue (ENET) specimens, and NPC biopsies by RT-PCR analysis. CYP2E1 was expressed in all NPC cell lines (6/6, including 7429) and ENET (6/6), and 80% of NPC biopsie (8/10). The fact that Human nasopharynx expresses CYP2E1 suggests that CYP2E1 may play an important role in the course of NPC by indirect carcinogens nitrosamines. To further evaluate the function of CYP2E1, the CYP2E1 was stably expressed in the cell line NIH 3T3/rtTA under a tetracycline-controlled transactivator. The expression of CYP2E1 was tightly regulated in a dose-dependent manner by Doxycycline (Dox) When the catalytic activity of CYP2E1 was assayed, the result showed that the generation of 6-hydroxychlorzoxazone (6-OH-CZ) from chlorzoxazone (CZ) was dose- and time-dependent on Dox addition to the medium. In the presence of 1 microg/ml Dox, the CZ 6-hydroxylase activity of the cell line was found to be 0.986 +/- 0.034 nmol/10(6) cells/h. The metabolic activation of Tet/3T3/2E1-6 cells was also assayed by N,N'-dinitrosopiperazine (DNP) cytotoxicity, and the viability of Tet/3T3/2E1-6 cells treated with Dox was lower than that of untreated cells with a significant difference between them in 80 and 160 microg/ml DNP (P ( 0.05, t test. This cell line will be useful not only to assess the metabolic characteristics of CYP2E1, but also will be useful to investigate the role of CYP2E1 in metabolic activation of carcinogenic nitrosamines in vitro.

PDH-E1alpha dephosphorylation and activation in human skeletal muscle during exercise

DEFF Research Database (Denmark)

Pilegaard, Henriette; Birk, Jesper Bratz; Sacchetti, Massimo

2006-01-01

. Phosphorylation had returned to resting levels at 3 h of exercise only in the control trial. Thus, an inverse association between PDH-E1a phosphorylation and PDHa activity exists. Short-term elevation in plasma FFA at rest increases PDH-E1a phosphorylation, but exercise overrules this effect of FFA on PDH-E1a...... extensor exercise at moderate intensity. During the 4-h resting period, activity of PDH in the active form (PDHa) did not change in either trial, yet phosphorylation of PDH-E1a site 1 (PDH-P1) and site 2 (PDH-P2) was elevated in the intralipid compared with the control trial. PDHa activity increased during...... exercise similarly in the two trials. After 3 h of exercise, PDHa activity remained elevated in the intralipid trial but returned to resting levels in the control trial. Accordingly, in both trials PDH-P1 and PDH-P2 decreased during exercise, and the decrease was more marked during intralipid infusion...

Direct and indirect targets of the E2A-PBX1 leukemia-specific fusion protein.

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Christofer Diakos

Full Text Available E2A-PBX1 is expressed as a result of the t(1;19 chromosomal translocation in nearly 5% of cases of childhood acute lymphoblastic leukemia. The E2A-PBX1 chimeric transcription factor contains the N-terminal transactivation domain of E2A (TCF3 fused to the C-terminal DNA-binding homeodomain of PBX1. While there is no doubt of its oncogenic potential, the mechanisms of E2A-PBX1-mediated pre-B cell transformation and the nature of direct E2A-PBX1 target genes and pathways remain largely unknown. Herein we used chromatin immunoprecipitation assays (ChIP-chip to identify direct targets of E2A-PBX1, and we used gene expression arrays of siRNA E2A-PBX1-silenced cells to evaluate changes in expression induced by the fusion protein. Combined ChIP-chip and expression data analysis gave rise to direct and functional targets of E2A-PBX1. Further we observe that the set of ChIP-chip identified E2A-PBX1 targets show a collective down-regulation trend in the E2A-PBX1 silenced samples compared to controls suggesting an activating role of this fusion transcription factor. Our data suggest that the expression of the E2A-PBX1 fusion gene interferes with key regulatory pathways and functions of hematopoietic biology. Among these are members of the WNT and apoptosis/cell cycle control pathways, and thus may comprise an essential driving force for the propagation and maintenance of the leukemic phenotype. These findings may also provide evidence of potentially attractive therapeutic targets.

Direct and indirect targets of the E2A-PBX1 leukemia-specific fusion protein.

Science.gov (United States)

Diakos, Christofer; Xiao, Yuanyuan; Zheng, Shichun; Kager, Leo; Dworzak, Michael; Wiemels, Joseph L

2014-01-01

E2A-PBX1 is expressed as a result of the t(1;19) chromosomal translocation in nearly 5% of cases of childhood acute lymphoblastic leukemia. The E2A-PBX1 chimeric transcription factor contains the N-terminal transactivation domain of E2A (TCF3) fused to the C-terminal DNA-binding homeodomain of PBX1. While there is no doubt of its oncogenic potential, the mechanisms of E2A-PBX1-mediated pre-B cell transformation and the nature of direct E2A-PBX1 target genes and pathways remain largely unknown. Herein we used chromatin immunoprecipitation assays (ChIP-chip) to identify direct targets of E2A-PBX1, and we used gene expression arrays of siRNA E2A-PBX1-silenced cells to evaluate changes in expression induced by the fusion protein. Combined ChIP-chip and expression data analysis gave rise to direct and functional targets of E2A-PBX1. Further we observe that the set of ChIP-chip identified E2A-PBX1 targets show a collective down-regulation trend in the E2A-PBX1 silenced samples compared to controls suggesting an activating role of this fusion transcription factor. Our data suggest that the expression of the E2A-PBX1 fusion gene interferes with key regulatory pathways and functions of hematopoietic biology. Among these are members of the WNT and apoptosis/cell cycle control pathways, and thus may comprise an essential driving force for the propagation and maintenance of the leukemic phenotype. These findings may also provide evidence of potentially attractive therapeutic targets.

Comunicações e Artigos Completos do 1º Encontro Internacional de Pesquisadores em Desporto, Psicologia e Saúde

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1º EIPEPS

2012-05-01

Full Text Available Este suplemento reúne as comunicações e artigos completos do 1º Encontro Internacional de Pesquisadores em Desporto, Psicologia e Saúde, que se realizou na cidade de Montes Claros, Brasil, entre os dias 12 e 16 de outubro de 2011.Este evento reuniu profissionais e estudantes das ciências da saúde, esporte e lazer, de vários países (Brasil, Portugal, USA, Chile e Moçambique, abrangendo as seguintes áreas temáticas: Ciências da Saúde, Gestão em Lazer, Atividade Física relacionada à Saúde, Educação relacionada à Saúde e Psicologia do Exercício e Saúde.

Design and optimization of N-acylhydrazone pyrimidine derivatives as E. coli PDHc E1 inhibitors: Structure-activity relationship analysis, biological evaluation and molecular docking study.

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He, Haifeng; Xia, Hongying; Xia, Qin; Ren, Yanliang; He, Hongwu

2017-10-15

By targeting the thiamin diphosphate (ThDP) binding site of Escherichia coli (E. coli) pyruvate dehydrogenase multienzyme complex E1 (PDHc E1), a series of novel 'open-chain' classes of ThDP analogs A, B, and C with N-acylhydrazone moieties was designed and synthesized to explore their activities against E. coli PHDc E1 in vitro and their inhibitory activity against microbial diseases were further evaluated in vivo. As a result, A1-23 exhibited moderate to potent inhibitory activities against E. coli PDHc E1 (IC 50 =0.15-23.55μM). The potent inhibitors A13, A14, A15, C2, had strong inhibitory activities with IC 50 values of 0.60, 0.15, 0.39 and 0.34μM against E. coli PDHc E1 and with good enzyme-selective inhibition between microorganisms and mammals. Especially, the most powerful inhibitor A14 could 99.37% control Xanthimonas oryzae pv. Oryzae. Furthermore, the binding features of compound A14 within E. coli PDHc E1 were investigated to provide useful insights for the further construction of new inhibitor by molecular docking, site-directed mutagenesis, and enzymatic assays. The results indicated that A14 had most powerful inhibition against E. coli PDHc E1 due to the establishment of stronger interaction with Glu571, Met194, Glu522, Leu264 and Phe602 at active site of E.coli PDHc E1. It could be used as a lead compound for further optimization, and may have potential as a new microbicide. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lysosomal-associated transmembrane protein 5 (LAPTM5 is a molecular partner of CD1e.

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Catherine Angénieux

Full Text Available The CD1e protein participates in the presentation of lipid antigens in dendritic cells. Its transmembrane precursor is transported to lysosomes where it is cleaved into an active soluble form. In the presence of bafilomycin, which inhibits vacuolar ATPase and consequently the acidification of endosomal compartments, CD1e associates with a 27 kD protein. In this work, we identified this molecular partner as LAPTM5. The latter protein and CD1e colocalize in trans-Golgi and late endosomal compartments. The quantity of LAPTM5/CD1e complexes increases when the cells are treated with bafilomycin, probably due to the protection of LAPTM5 from lysosomal proteases. Moreover, we could demonstrate that LAPTM5/CD1e association occurs under physiological conditions. Although LAPTM5 was previously shown to act as a platform recruiting ubiquitin ligases and facilitating the transport of receptors to lysosomes, we found no evidence that LATPM5 controls either CD1e ubiquitination or the generation of soluble lysosomal CD1e proteins. Notwithstanding these last observations, the interaction of LAPTM5 with CD1e and their colocalization in antigen processing compartments both suggest that LAPTM5 might influence the role of CD1e in the presentation of lipid antigens.

Deficiency of cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 accelerates atherogenesis in apolipoprotein E-deficient mice

International Nuclear Information System (INIS)

Akyuerek, Levent M.; Boehm, Manfred; Olive, Michelle; Zhou, Alex-Xianghua; San, Hong; Nabel, Elizabeth G.

2010-01-01

Cyclin-dependent kinase inhibitors, p21 Cip1 and p27 Kip1 , are upregulated during vascular cell proliferation and negatively regulate growth of vascular cells. We hypothesized that absence of either p21 Cip1 or p27 Kip1 in apolipoprotein E (apoE)-deficiency may increase atherosclerotic plaque formation. Compared to apoE -/- aortae, both apoE -/- /p21 -/- and apoE -/- /p27 -/- aortae exhibited significantly more atherosclerotic plaque following a high-cholesterol regimen. This increase was particularly observed in the abdominal aortic regions. Deficiency of p27 Kip1 accelerated plaque formation significantly more than p21 -/- in apoE -/- mice. This increased plaque formation was in parallel with increased intima/media area ratios. Deficiency of p21 Cip1 and p27 Kip1 accelerates atherogenesis in apoE -/- mice. These findings have significant implications for our understanding of the molecular basis of atherosclerosis associated with excessive proliferation of vascular cells.

HLA Class I-Mediated HIV-1 Control in Vietnamese Infected with HIV-1 Subtype A/E.

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Chikata, Takayuki; Tran, Giang Van; Murakoshi, Hayato; Akahoshi, Tomohiro; Qi, Ying; Naranbhai, Vivek; Kuse, Nozomi; Tamura, Yoshiko; Koyanagi, Madoka; Sakai, Sachiko; Nguyen, Dung Hoai; Nguyen, Dung Thi; Nguyen, Ha Thu; Nguyen, Trung Vu; Oka, Shinichi; Martin, Maureen P; Carrington, Mary; Sakai, Keiko; Nguyen, Kinh Van; Takiguchi, Masafumi

2018-03-01

HIV-1-specific cytotoxic T cells (CTLs) play an important role in the control of HIV-1 subtype B or C infection. However, the role of CTLs in HIV-1 subtype A/E infection still remains unclear. Here we investigated the association of HLA class I alleles with clinical outcomes in treatment-naive Vietnamese infected with subtype A/E virus. We found that HLA-C*12:02 was significantly associated with lower plasma viral loads (pVL) and higher CD4 counts and that the HLA-A*29:01-B*07:05-C*15:05 haplotype was significantly associated with higher pVL and lower CD4 counts than those for individuals without these respective genotypes. Nine Pol and three Nef mutations were associated with at least one HLA allele in the HLA-A*29:01-B*07:05-C*15:05 haplotype, with a strong negative correlation between the number of HLA-associated Pol mutations and CD4 count as well as a positive correlation with pVL for individuals with these HLA alleles. The results suggest that the accumulation of mutations selected by CTLs restricted by these HLA alleles affects HIV control. IMPORTANCE Most previous studies on HLA association with disease progression after HIV-1 infection have been performed on cohorts infected with HIV-1 subtypes B and C, whereas few such population-based studies have been reported for cohorts infected with the Asian subtype A/E virus. In this study, we analyzed the association of HLA class I alleles with clinical outcomes for 536 HIV-1 subtype A/E-infected Vietnamese individuals. We found that HLA-C*12:02 is protective, while the HLA haplotype HLA-A*29:01-B*07:05-C*15:05 is deleterious. The individuals with HIV-1 mutations associated with at least one of the HLA alleles in the deleterious HLA haplotype had higher plasma viral loads and lower CD4 counts than those of individuals without the mutations, suggesting that viral adaptation and escape from HLA-mediated immune control occurred. The present study identifies a protective allele and a deleterious haplotype for HIV-1

Spectroscopy of virtual photons in Ar+KCl collisions at E{sub kin}=1.76 AGeV; Spektroskopie virtueller Photonen in Ar+KCl Stoessen bei E{sub kin}=1,76 AGeV

Energy Technology Data Exchange (ETDEWEB)

Jurkovic, Martin

2010-01-14

The objective of this thesis is the analysis of virtual photon emission originating from the decays of the short lived hadrons produced in Ar+KCl collisions at E{sub kin}=1.76 AGeV. The measured observables were the reconstructed e{sup +}e{sup -} pairs and their kinematic distributions. The data were recorded with the HADES spectrometer assembled at GSI Helmholtzzentrum fuer Schwerionenforschung GmbH in Darmstadt, Germany. Due to the considerably higher combinatorial background originating from the {gamma}-conversion as compared to that from light collision systems (p+p,C+C) investigated so far with HADES, a new method for identification and suppression of conversion electrons using the signal pattern in the RICH-detector was studied. An improvement of signal to background ratio (S/B) reaching 30% was achieved. For the procedure of calculating the e{sup +}/e{sup -} track efficiencies a detailed study of RICH detector signals was performed, leading to an overall improved description of ring observables in the simulation. In total, 32545pm 385 e{sup +}e{sup -} signal pairs with an opening angle {alpha}{sub ee} > 15 and 0.1 < p{sub e} < 1.1 GeV/c were identified, with 7402{+-}222 pairs in the so-called {eta} mass region (0.15 < M{sub ee} < 0.55 GeV/c{sup 2}) and 253{+-}25 for masses M{sub ee} > 0.55 GeV/c{sup 2}. A clear signal from direct {omega} decay with S/B {proportional_to}1 was identified for the first time in the SIS18 energy regime. The extraction of the {omega} yield per produced {pi}{sup 0} results in N({omega})/N({pi}{sup 0}) {approx} (4,5 {+-} 2,5(stat) {+-} 2(sys)) .10{sup -8}. The e{sup +}e{sup -} production in the {eta} mass region was compared to the expected {eta} Dalitz decay {eta}{yields}{gamma}e{sup +}e{sup -} contribution. The measured e{sup +}e{sup -} yield is higher by a factor F = 3.4{+-}0.2(stat){+-}0.6(sys){+-}0.9({eta}) as compared to the {eta} production. The excitation function of the extra e{sup +}/e{sup -} sources shows similar energy

Comparison of methods by TLC and HPTLC for determination of aflatoxin M1 in milk and B1 in eggs Comparação de metodologia para análise de aflatoxina M1 em leite e aflatoxina B1 em ovos por CCD e CCDAE

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V. M. Scussel

2003-12-01

Full Text Available Milk and egg matrixes were assayed for aflatoxin M1 (AFM1 and B1 (AFB1 respectively, by AOAC official and modified methods with detection and quantification by thin layer chromatography (TLC and high performance thin layer chromatography (HPTLC. The modified methods: Blanc followed by Romer, showed to be most appropriate for AFM1 analysis in milk. Both methods reduced emulsion formation, produced cleaner extracts, no streaking spots, precision and accuracy improved, especially when quantification was performed by HPTLC. The use of ternary mixture in the Blanc Method was advantageous as the solvent could extract AFM1 directly from the first stage (extraction, leaving other compounds in the binary mixture layer, avoiding emulsion formation, thus reducing toxin loss. The relative standard deviation (RSD% values were low, 16 and 7% when TLC and HPTLC were used, with a mean recovery of 94 and 97%, respectively. As far as egg matrix and final extract are concerned, both methods evaluated for AFB1 need further studies. Although that matrix leads to emulsion with consequent loss of toxin, the Romer modified presented a reasonable clean extract (mean recovery of 92 and 96% for TLC and HPTLC, respectively. Most of the methods studied did not performed as expected mainly due to the matrixes high content of triglicerides (rich on saturated fatty acids, cholesterol, carotene and proteins. Although nowadays most methodology for AFM1 is based on HPLC, TLC determination (Blanc and Romer modified for AFM1 and AFB1 is particularly recommended to those, inexperienced in food and feed mycotoxins analysis and especially who cannot afford to purchase sophisticated (HPLC,HPTLC instrumentation.Aflatoxinas M1 (AFM1 e B1 (AFB1 foram analisadas em leite e ovos respectivamente, por diferentes métodos oficiais da AOAC e modificações usando detecção por cromatografia em camada delgada (CCD e CCD de alta eficiência (CCDAE. Os métodos modificados: Blanc e Romer

40 CFR 180.1126 - Codlure, (E,E)-8,10-Dodecadien-1-ol; exemption from the requirement of a tolerance.

Science.gov (United States)

2010-07-01

... RESIDUES IN FOOD Exemptions From Tolerances § 180.1126 Codlure, (E,E)-8,10-Dodecadien-1-ol; exemption from... construction that they are readily recognized post-application. (2) The dispensers must be applied discretely...

Expression of plasmid-based shRNA against the E1 and nsP1 genes effectively silenced Chikungunya virus replication.

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Shirley Lam

Full Text Available BACKGROUND: Chikungunya virus (CHIKV is a re-emerging alphavirus that causes chikungunya fever and persistent arthralgia in humans. Currently, there is no effective vaccine or antiviral against CHIKV infection. Therefore, this study evaluates whether RNA interference which targets at viral genomic level may be a novel antiviral strategy to inhibit the medically important CHIKV infection. METHODS: Plasmid-based small hairpin RNA (shRNA was investigated for its efficacy in inhibiting CHIKV replication. Three shRNAs designed against CHIKV Capsid, E1 and nsP1 genes were transfected to establish stable shRNA-expressing cell clones. Following infection of stable shRNA cells clones with CHIKV at M.O.I. 1, viral plaque assay, Western blotting and transmission electron microscopy were performed. The in vivo efficacy of shRNA against CHIKV replication was also evaluated in a suckling murine model of CHIKV infection. RESULTS: Cell clones expressing shRNAs against CHIKV E1 and nsP1 genes displayed significant inhibition of infectious CHIKV production, while shRNA Capsid demonstrated a modest inhibitory effect as compared to scrambled shRNA cell clones and non-transfected cell controls. Western blot analysis of CHIKV E2 protein expression and transmission electron microscopy of shRNA E1 and nsP1 cell clones collectively demonstrated similar inhibitory trends against CHIKV replication. shRNA E1 showed non cell-type specific anti-CHIKV effects and broad-spectrum silencing against different geographical strains of CHIKV. Furthermore, shRNA E1 clones did not exert any inhibition against Dengue virus and Sindbis virus replication, thus indicating the high specificity of shRNA against CHIKV replication. Moreover, no shRNA-resistant CHIKV mutant was generated after 50 passages of CHIKV in the stable cell clones. More importantly, strong and sustained anti-CHIKV protection was conferred in suckling mice pre-treated with shRNA E1. CONCLUSION: Taken together, these

MicroRNA-16 Modulates HuR Regulation of Cyclin E1 in Breast Cancer Cells

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Xun Guo

2015-03-01

Full Text Available RNA binding protein (RBPs and microRNAs (miRNAs or miRs are post-transcriptional regulators of gene expression that are implicated in development of cancers. Although their individual roles have been studied, the crosstalk between RBPs and miRNAs is under intense investigation. Here, we show that in breast cancer cells, cyclin E1 upregulation by the RBP HuR is through specific binding to regions in the cyclin E1 mRNA 3' untranslated region (3'UTR containing U-rich elements. Similarly, miR-16 represses cyclin E1, dependent on its cognate binding sites in the cyclin E1 3'UTR. Evidence in the literature indicates that HuR can regulate miRNA expression and recruit or dissociate RNA-induced silencing complexes (RISC. Despite this, miR-16 and HuR do not affect the other’s expression level or binding to the cyclin E1 3'UTR. While HuR overexpression partially blocks miR-16 repression of a reporter mRNA containing the cyclin E1 3'UTR, it does not block miR-16 repression of endogenous cyclin E1 mRNA. In contrast, miR-16 blocks HuR-mediated upregulation of cyclin E1. Overall our results suggest that miR-16 can override HuR upregulation of cyclin E1 without affecting HuR expression or association with the cyclin E1 mRNA.

The effect of lycopene on the total cytochrome P450, CYP1A2 and CYP2E1

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Melva Louisa

2009-12-01

Full Text Available Aim: Some carotenoids such as canthaxantin, astaxanthin and beta apo-8’-carotenal were reported to have modulatoryeffect on the cytochrome P450. The present study was conducted to investigate the effects of lycopene, a nonprovitamin A carotenoid, on microsomal cytochrome P450, CYP1A2 and CYP2E1.Methods: Total cytochrome P450 levels, CYP1A2 and CYP2E1-catalyzed reactions (acetanilide 4-hydroxylation and p-nitrophenol hydroxylation were studied in the liver microsomes of male Sprague Dawley rats. Microsomes were prepared using differential centrifugation combined with calcium aggregation method. Lycopene was orally administered in the dosages of 0, 25, 50 or 100 mg/kgBW/day for 14 days in a repeated fashion. Data were analyzed using ANOVA test.Results: Total cytochrome P450 level and acetanilide 4-hydroxylase activity were unaffected by any of the treatments. The CYP2E1 probe enzyme (p-nitrophenol hydroxylase was significantly reduced by repeated administration of 100mg/ kgBW/day lycopene (7.88 + 2.04 vs 12.26 + 2.77 n mol/min/mg prot.Conclusion: The present results suggest that lycopene does not affect the total cytochrome P450 or CYP1A2 activity but it inhibits the activity of CYP2E1 (p-nitrophenol hydroxylase in the rat. (Med J Indones 2009; 18: 233-8Keywords: lycopene, cytochrome P450, CYP1A2, CYP2E1

75 FR 53861 - Airworthiness Directives; Robert E. Rust, Jr. Model DeHavilland DH.C1 Chipmunk 21, DH.C1 Chipmunk...

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2010-09-02

... Airworthiness Directives; Robert E. Rust, Jr. Model DeHavilland DH.C1 Chipmunk 21, DH.C1 Chipmunk 22, and DH.C1...). ACTION: Final rule. SUMMARY: We are adopting a new airworthiness directive (AD) for all Robert E. Rust... CFR part 39) to include an AD that would apply to all Robert E. Rust, Jr. Models DeHavilland DH.C1...

Novel CYP2E1 haplotype identified in a South African cohort

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Laura J. Heathfield

2014-09-01

Full Text Available Alcohol abuse accounts for approximately 2.5 million deaths annually and is the third highest risk factor for disease and disability. Alcohol is metabolised by polymorphic enzymes and the status of an individual with respect to alcohol metabolising enzymes may have forensic relevance in post-mortems. Baseline frequencies of gene variants involved in alcohol metabolism need to be established to aid the identification of suitable population-specific polymorphisms to genotype during molecular autopsies. The principal alcohol metabolising enzymes include alcohol dehydrogenase (ADH, aldehyde dehydrogenase (ALDH and cytochrome P450 2E1 (CYP2E1. Six single nucleotide polymorphisms (SNPs – rs1229984G>A and rs2066702C>T in ADH1B, rs671G>A in ALDH2, and rs3813867G>C, rs2031920C>T and rs6413432T>A in CYP2E1 – were genotyped in 150 individuals from four South African populations: Xhosa, Zulu, South African white and South African coloured. Allele frequencies for each SNP in the four population groups were 0–10% for rs1229984A, 2–12% for rs2066702T, 0–2% for rs671A, 1–4% for rs3813867C, 0–1% for rs2031920T and 3–15% for rs6413432A. Haplotype analysis revealed a novel combination of three SNPs in CYP2E1 whose effects on alcohol metabolism need further investigation. Establishment of baseline frequencies adds to our knowledge of genetic variation in alcohol metabolising enzymes and additional research is required to determine the functional significance of this novel CYP2E1 haplotype.

Low energy electron irradiation induced deep level defects in 6H-SiC: The implication for the microstructure of the deep levels E1/E2

International Nuclear Information System (INIS)

Chen, X.D.; Fung, S.; Beling, C.D.; Lui, M.K.; Ling, C.C.; Yang, C.L.; Ge, W.K.; Wang, J.N.; Gong, M.

2004-01-01

N-type 6H-SiC samples irradiated with electrons having energies of E e =0.2, 0.3, 0.5, and 1.7 were studied by deep level transient technique. No deep level was detected at below 0.2 MeV irradiation energy while for E e ≥0.3 MeV, deep levels ED1, E 1 /E 2 , and E i appeared. By considering the minimum energy required to displace the C atom or the Si atom in the SiC lattice, it is concluded that generation of the deep levels E 1 /E 2 , as well as ED1 and E i , involves the displacement of the C atom in the SiC lattice

RIGOROUS PHOTOGRAMMETRIC PROCESSING OF CHANG'E-1 AND CHANG'E-2 STEREO IMAGERY FOR LUNAR TOPOGRAPHIC MAPPING

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K. Di

2012-07-01

Full Text Available Chang'E-1(CE-1 and Chang'E-2(CE-2 are the two lunar orbiters of China's lunar exploration program. Topographic mapping using CE-1 and CE-2 images is of great importance for scientific research as well as for preparation of landing and surface operation of Chang'E-3 lunar rover. In this research, we developed rigorous sensor models of CE-1 and CE-2 CCD cameras based on push-broom imaging principle with interior and exterior orientation parameters. Based on the rigorous sensor model, the 3D coordinate of a ground point in lunar body-fixed (LBF coordinate system can be calculated by space intersection from the image coordinates of con-jugate points in stereo images, and the image coordinates can be calculated from 3D coordinates by back-projection. Due to uncer-tainties of the orbit and the camera, the back-projected image points are different from the measured points. In order to reduce these inconsistencies and improve precision, we proposed two methods to refine the rigorous sensor model: 1 refining EOPs by correcting the attitude angle bias, 2 refining the interior orientation model by calibration of the relative position of the two linear CCD arrays. Experimental results show that the mean back-projection residuals of CE-1 images are reduced to better than 1/100 pixel by method 1 and the mean back-projection residuals of CE-2 images are reduced from over 20 pixels to 0.02 pixel by method 2. Consequently, high precision DEM (Digital Elevation Model and DOM (Digital Ortho Map are automatically generated.

26 CFR 1.404(e)-1A - Contributions on behalf of a self-employed individual to or under a qualified pension, annuity...

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2010-04-01

... individual to or under a qualified pension, annuity, or profit-sharing plan. 1.404(e)-1A Section 1.404(e)-1A...) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.404(e)-1A Contributions on behalf of a self-employed individual to or under a qualified pension, annuity, or profit-sharing plan. (a) In...

STABILITAS EPIGALOKATEKIN GALAT DALAM KRIM EKSTRAK TEH HIJAU DENGAN VARIASI KONSENTRASI ANTIOKSIDAN VITAMIN C 1% DAN VITAMIN E 1%

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Nining Sugihartini

2016-11-01

Full Text Available Epigallocatechingallate (EGCG in green tea extract has activity as an anti-inflammatory agent. On the other hand the stability of EGCG is poor because of the oxidation. The aim of this study was to determine the influence of Vitamine C and Vitamine E in formulation of green tea extract cream to the stabiliy of EGCG. The green tea extract was obtained from the extraction process by infundation followed by fractination with ethyl acetate as the solvent. The three formulas were compiled in similar composition with the concentration of vitamine C 1% (FI, Vitamine E 1% (FII and there was no Vitamine C and Vitamine E (FIII as a control. The EGCG level was determinated by TLC-densitometry methode. The stability parameter was determinated by calculated of the Q10 of each formula. The result of this study showed that the parameter of t90 of EGCG with Vitamine C 1%, Vitamine E 1% and control addition were 0.0108 hours, 0.0087 hours, 0.0084 hours, respectively. Stability of EGCG in green tea leaf extract cream with addition of the vitamin C 1% was higher than it stability with the addition of vitamin E 1%. The concentration of Vitamin C 1% was the optimum concentration as antioxidant in formulation of green tea extract cream.

Estaquia caulinar herbácea e semilenhosa de Drimys brasiliensis1

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Luciele Milani Zem

Full Text Available Drimys brasiliensis conhecida como cataia, é uma espécie arbórea nativa da Mata Atlântica. Tem importância fitoquímica, fitoterapêutica, aromática e econômica, utilizada na fabricação de licores, condimentos, dentre outros. É considerada uma espécie de difícil multiplicação via sementes, apresentando dormência por imaturidade embrionária. Assim, objetivou-se estudar a propagação vegetativa por meio da indução do enraizamento de estacas herbáceas e semilenhosas submetidas a diferentes concentrações de ácido indolbutírico (IBA, coletadas em duas épocas do ano (junho/2011 e dezembro/2011. Foram utilizados os tratamentos: testemunha (100% água, 0 (50% água e 50% álcool; 1.500; 3.000 e 6.000 mg L-1IBA (em solução hidroalcoólica 50% para o inverno e, no verão, os mesmos tratamentos, exceto 0 mg L-1IBA. Foi conduzido um experimento em delineamento inteiramente casualizado, em esquema fatorial de 5 concentrações x 2 tipos de estacas em junho/2011; e outro experimento com 4 concentrações x 2 épocas de coleta (estacas de junho/2011 e estacas de dezembro/2011 Após 120 dias em casa de vegetação, avaliou-se a porcentagem de estacas enraizadas, número de raízes/estaca, comprimento médio de raízes/estaca, porcentagem estacas vivas, com calos, mortas, com novas brotações e que mantiveram as folhas iniciais. A aplicação de IBA não influenciou nenhuma das variáveis estudadas. Estacas herbáceas apresentaram melhor enraizamento (46,75% quando comparadas às semilenhosas (34,44%. A coleta realizada em dezembro/2011 apresentou maior número de raízes/estaca (5,47 porém maior mortalidade (29,05% que em junho/2011 (4,25 e 12,19%, respectivamente. Sendo assim, para o enraizamento de cataia é indicada a utilização de estacas caulinares herbáceas, coletadas em épocas frias.

Apolipoprotein E and presenilin-1 genotypes in Huntington's disease.

Science.gov (United States)

Panas, M; Avramopoulos, D; Karadima, G; Petersen, M B; Vassilopoulos, D

1999-07-01

Huntington's disease (HD) is an autosomal dominant degenerative disease of the central nervous system manifested by involuntary movements (chorea), psychiatric manifestations, and cognitive impairment with a variable age at onset. This variability is mainly attributed to genetic factors. The so-called aging genes [e.g., those for apolipoprotein E (APOE) and presenilin-1 (PS-1) have been implicated in determining the age at onset of Alzheimer's disease, a disease sharing common clinical features with HD. In 60 unrelated patients suffering from HD (mean age at onset 40.1 years, range 20-65) we determined number of CAG repeats and the distribution of the APOE alleles (epsilon2, epsilon3, epsilon4) and PS-1 alleles. The results showed that: (a) The age at onset was higher in the group of patients with the epsilon4 allele (51.6 vs. 38.0 P<0.002), (b) The correlation between the age at onset and the number of CAG repeats was strong in patients with the epsilon3/epsilon3 genotype while it was not detected in patients with epsilon3/epsilon4 genotype. (c) No correlation was found between age at onset and PS-1 alleles. In conclusion, APOE seems to be a significant factor influencing the age at onset of Huntington's disease.

Unequal distribution of RT-PCR artifacts along the E1-E2 region of Hepatitis C virus.

Science.gov (United States)

Domingo-Calap, Pilar; Sentandreu, Vicente; Bracho, Maria Alma; González-Candelas, Fernando; Moya, Andrés; Sanjuán, Rafael

2009-10-01

Although viral variability studies have focused traditionally on consensus sequences, the relevance of molecular clone sequences for studying viral evolution at the intra-host level is being increasingly recognized. However, for this approach to be reliable, RT-PCR artifacts do not have to contribute excessively to the observed variability. Molecular clone sequences were obtained from an in vitro transcript to estimate the maximum error rate associated to RT-PCR for the Hepatitis C virus (HCV) E1-E2 region. On average, the frequency of RT-PCR errors was one order of magnitude lower than the level of intra-host genetic variability observed in samples from an HCV outbreak. However, RT-PCR errors were not distributed evenly along the E1-E2 region and were concentrated heavily in the hypervariable region 2 (HVR 2). Although it is concluded that RT-PCR molecular clone sequences are reliable, these results warn against extrapolation of RT-PCR error rates to different genome regions. The data suggest that the RNA sequence context or secondary structure can determine the fidelity of in vitro transcription or reverse transcription. Potentially, these factors might also modify the fidelity of the viral polymerase.

Plasmid ColE1 as a Molecular Vehicle for Cloning and Amplification of DNA

Science.gov (United States)

Hershfield, Vickers; Boyer, Herbert W.; Yanofsky, Charles; Lovett, Michael A.; Helinski, Donald R.

1974-01-01

DNA fragments obtained from EcoRI endonuclease digestion of bacteriophage ϕ80pt190 (trp+) and the plasmid ColE1 were covalently joined with polynucleotide ligase. Transformation of Escherichia coli trp- strains to tryptophan independence with the recombined DNA selected for reconstituted ColE1 plasmids containing the tryptophan operon and the ϕ80 immunity region. Similarly, an EcoRI endonuclease generated fragment of plasmid pSC105 DNA containing the genetic determinant of kanamycin resistance was inserted into the ColE1 plasmid and recovered in E. coli. The plasmids containing the trp operon (ColE1-trp) and the kanamycin resistance gene were maintained under logarithmic growth conditions at a level of 25-30 copies per cell and accumulate to the extent of several hundred copies per cell in the presence of chloramphenicol. Cells carrying the ColE1-trp plasmid determined the production of highly elevated levels of trp operon-specific mRNA and tryptophan biosynthetic enzymes. Images PMID:4610576

p21/Cyclin E pathway modulates anticlastogenic function of Bmi-1 in cancer cells

Science.gov (United States)

Deng, Wen; Zhou, Yuan; Tiwari, Agnes FY; Su, Hang; Yang, Jie; Zhu, Dandan; Lau, Victoria Ming Yi; Hau, Pok Man; Yip, Yim Ling; Cheung, Annie LM; Guan, Xin-Yuan; Tsao, Sai Wah

2015-01-01

Apart from regulating stem cell self-renewal, embryonic development and proliferation, Bmi-1 has been recently reported to be critical in the maintenance of genome integrity. In searching for novel mechanisms underlying the anticlastogenic function of Bmi-1, we observed, for the first time, that Bmi-1 positively regulates p21 expression. We extended the finding that Bmi-1 deficiency induced chromosome breaks in multiple cancer cell models. Interestingly, we further demonstrated that knockdown of cyclin E or ectopic overexpression of p21 rescued Bmi-1 deficiency-induced chromosome breaks. We therefore conclude that p21/cyclin E pathway is crucial in modulating the anticlastogenic function of Bmi-1. As it is well established that the overexpression of cyclin E potently induces genome instability and p21 suppresses the function of cyclin E, the novel and important implication from our findings is that Bmi-1 plays an important role in limiting genomic instability in cylin E-overexpressing cancer cells by positive regulation of p21. PMID:25131797

Mapping the human translation elongation factor eEF1H complex using the yeast two-hybrid system

DEFF Research Database (Denmark)

Mansilla, Francisco; Friis, Irene; Jadidi, Mandana

2002-01-01

In eukaryotes, the eukaryotic translation elongation factor eEF1A responsible for transporting amino-acylated tRNA to the ribosome forms a higher-order complex, eEF1H, with its guanine-nucleotide-exchange factor eEF1B. In metazoans, eEF1B consists of three subunits: eEF1B alpha, eEF1B eta and eEF1B...... of in vitro experiments have been proposed for the macromolecular organization of the eEF1H complex. However, these models differ in various aspects. This might be due to the difficulties of handling, particularly the eEF1B beta and eEF1B gamma subunits in vitro. Here, the human eEF1H complex is for the first...... gamma:eEF1B beta, where the last was observed using a three-hybrid approach. Surprisingly, eEF1A2 showed no or only little affinity for the guanine-nucleotide-exchange factors. Truncated versions of the subunits of eEF1B were used to orientate these subunits within the resulting model. The model unit...

Heating, Ventilation, Air Conditioning, and Refrigeration (HVAC/R), AFSC 3E1X1. OSSN 2368

National Research Council Canada - National Science Library

1999-01-01

Survey Coverage: The Heating, Ventilation, Air Conditioning, and Refrigeration (HVAC/R) career ladder, AFSC 3E1X1, was surveyed to gather data needed to guide the development and evaluation of training...

Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication In Vivo.

Science.gov (United States)

Bergvall, Monika; Gagnon, David; Titolo, Steve; Lehoux, Michaël; D'Abramo, Claudia M; Melendy, Thomas; Archambault, Jacques

2016-01-06

The papillomavirus (PV) E1 helicase contains a conserved C-terminal domain (CTD), located next to its ATP-binding site, whose function in vivo is still poorly understood. The CTD is comprised of an alpha helix followed by an acidic region (AR) and a C-terminal extension termed the C-tail. Recent biochemical studies on bovine papillomavirus 1 (BPV1) E1 showed that the AR and C-tail regulate the oligomerization of the protein into a double hexamer at the origin. In this study, we assessed the importance of the CTD of human papillomavirus 11 (HPV11) E1 in vivo, using a cell-based DNA replication assay. Our results indicate that combined deletion of the AR and C-tail drastically reduces DNA replication, by 85%, and that further truncation into the alpha-helical region compromises the structural integrity of the E1 helicase domain and its interaction with E2. Surprisingly, removal of the C-tail alone or mutation of highly conserved residues within the domain still allows significant levels of DNA replication (55%). This is in contrast to the absolute requirement for the C-tail reported for BPV1 E1 in vitro and confirmed here in vivo. Characterization of chimeric proteins in which the AR and C-tail from HPV11 E1 were replaced by those of BPV1 indicated that while the function of the AR is transferable, that of the C-tail is not. Collectively, these findings define the contribution of the three CTD subdomains to the DNA replication activity of E1 in vivo and suggest that the function of the C-tail has evolved in a PV type-specific manner. While much is known about hexameric DNA helicases from superfamily 3, the papillomavirus E1 helicase contains a unique C-terminal domain (CTD) adjacent to its ATP-binding site. We show here that this CTD is important for the DNA replication activity of HPV11 E1 in vivo and that it can be divided into three functional subdomains that roughly correspond to the three conserved regions of the CTD: an alpha helix, needed for the structural

Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication In Vivo

Science.gov (United States)

Bergvall, Monika; Gagnon, David; Titolo, Steve; Lehoux, Michaël; D'Abramo, Claudia M.

2016-01-01

ABSTRACT The papillomavirus (PV) E1 helicase contains a conserved C-terminal domain (CTD), located next to its ATP-binding site, whose function in vivo is still poorly understood. The CTD is comprised of an alpha helix followed by an acidic region (AR) and a C-terminal extension termed the C-tail. Recent biochemical studies on bovine papillomavirus 1 (BPV1) E1 showed that the AR and C-tail regulate the oligomerization of the protein into a double hexamer at the origin. In this study, we assessed the importance of the CTD of human papillomavirus 11 (HPV11) E1 in vivo, using a cell-based DNA replication assay. Our results indicate that combined deletion of the AR and C-tail drastically reduces DNA replication, by 85%, and that further truncation into the alpha-helical region compromises the structural integrity of the E1 helicase domain and its interaction with E2. Surprisingly, removal of the C-tail alone or mutation of highly conserved residues within the domain still allows significant levels of DNA replication (55%). This is in contrast to the absolute requirement for the C-tail reported for BPV1 E1 in vitro and confirmed here in vivo. Characterization of chimeric proteins in which the AR and C-tail from HPV11 E1 were replaced by those of BPV1 indicated that while the function of the AR is transferable, that of the C-tail is not. Collectively, these findings define the contribution of the three CTD subdomains to the DNA replication activity of E1 in vivo and suggest that the function of the C-tail has evolved in a PV type-specific manner. IMPORTANCE While much is known about hexameric DNA helicases from superfamily 3, the papillomavirus E1 helicase contains a unique C-terminal domain (CTD) adjacent to its ATP-binding site. We show here that this CTD is important for the DNA replication activity of HPV11 E1 in vivo and that it can be divided into three functional subdomains that roughly correspond to the three conserved regions of the CTD: an alpha helix, needed