TopBP1 associates with NBS1 and is involved in homologous recombination repair

International Nuclear Information System (INIS)

Morishima, Ken-ichi; Sakamoto, Shuichi; Kobayashi, Junya; Izumi, Hideki; Suda, Tetsuji; Matsumoto, Yoshiyuki; Tauchi, Hiroshi; Ide, Hiroshi; Komatsu, Kenshi; Matsuura, Shinya

2007-01-01

TopBP1 is involved in DNA replication and DNA damage checkpoint. Recent studies have demonstrated that TopBP1 is a direct positive effecter of ATR. However, it is not known how TopBP1 recognizes damaged DNA. Here, we show that TopBP1 formed nuclear foci after exposure to ionizing radiation, but such TopBP1 foci were abolished in Nijmegen breakage syndrome cells. We also show that TopBP1 physically associated with NBS1 in vivo. These results suggested that NBS1 might regulate TopBP1 recruitment to the sites of DNA damage. TopBP1-depleted cells showed hypersensitivity to Mitomycin C and ionizing radiation, an increased frequency of sister-chromatid exchange level, and a reduced frequency of DNA double-strand break induced homologous recombination repair. Together, these results suggested that TopBP1 might be a mediator of DNA damage signaling from NBS1 to ATR and promote homologous recombination repair

Homology modeling of Homo sapiens lipoic acid synthase: Substrate docking and insights on its binding mode.

Science.gov (United States)

Krishnamoorthy, Ezhilarasi; Hassan, Sameer; Hanna, Luke Elizabeth; Padmalayam, Indira; Rajaram, Rama; Viswanathan, Vijay

2017-05-07

Lipoic acid synthase (LIAS) is an iron-sulfur cluster mitochondrial enzyme which catalyzes the final step in the de novo pathway for the biosynthesis of lipoic acid, a potent antioxidant. Recently there has been significant interest in its role in metabolic diseases and its deficiency in LIAS expression has been linked to conditions such as diabetes, atherosclerosis and neonatal-onset epilepsy, suggesting a strong inverse correlation between LIAS reduction and disease status. In this study we use a bioinformatics approach to predict its structure, which would be helpful to understanding its role. A homology model for LIAS protein was generated using X-ray crystallographic structure of Thermosynechococcus elongatus BP-1 (PDB ID: 4U0P). The predicted structure has 93% of the residues in the most favour region of Ramachandran plot. The active site of LIAS protein was mapped and docked with S-Adenosyl Methionine (SAM) using GOLD software. The LIAS-SAM complex was further refined using molecular dynamics simulation within the subsite 1 and subsite 3 of the active site. To the best of our knowledge, this is the first study to report a reliable homology model of LIAS protein. This study will facilitate a better understanding mode of action of the enzyme-substrate complex for future studies in designing drugs that can target LIAS protein. Copyright © 2017 Elsevier Ltd. All rights reserved.

ORF Alignment: NC_004113 [GENIUS II[Archive

Lifescience Database Archive (English)

Full Text Available ... elongatus BP-1] ... Length = 211 ... Query: 1 ... MATLEFLTFPDPAIAADHTLLLLHGWGANAADLISLGPLLAPHAQIYAAEAPF...PHPYVAQ 60 ... MATLEFLTFPDPAIAADHTLLLLHGWGANAADLISLGPLLAPHAQIYAAEAPFPHPYVA...Q Sbjct: 1 ... MATLEFLTFPDPAIAADHTLLLLHGWGANAADLISLGPLLAPHAQIYAAEAPFPHPYVAQ 60 ... Query: 121 AVGLRLPLAGLLVFSGYLV

Evaluation of fungal- and photo-degradation as potential treatments for the removal of sunscreens BP3 and BP1

International Nuclear Information System (INIS)

Gago-Ferrero, Pablo; Badia-Fabregat, Marina; Olivares, Alba; Piña, Benjamin; Blánquez, Paqui; Vicent, Teresa; Caminal, Gloria; Díaz-Cruz, M. Silvia

2012-01-01

Photodecomposition might be regarded as one of the most important abiotic factors affecting the fate of UV absorbing compounds in the environment and photocatalysis has been suggested as an effective method to degrade organic pollutants. However, UV filters transformation appears to be a complex process, barely addressed to date. The white rot fungus Trametes versicolor is considered as a promising alternative to conventional aerobic bacterial degradation, as it is able to metabolise a wide range of xenobiotics. This study focused on both degradation processes of two widely used UV filters, benzophenone-3 (BP3) and benzophenone-1 (BP1). Fungal treatment resulted in the degradation of more than 99% for both sunscreens in less than 24 h, whereas photodegradation was very inefficient, especially for BP3, which remained unaltered upon 24 h of simulated sunlight irradiation. Analysis of metabolic compounds generated showed BP1 as a minor by-product of BP3 degradation by T. versicolor while the main intermediate metabolites were glycoconjugate derivatives. BP1 and BP3 showed a weak, but significant estrogenic activity (EC50 values of 0.058 mg/L and 12.5 mg/L, respectively) when tested by recombinant yeast assay (RYA), being BP1 200-folds more estrogenic than BP3. Estrogenic activity was eliminated during T. versicolor degradation of both compounds, showing that none of the resulting metabolites possessed significant estrogenic activity at the concentrations produced. These results demonstrate the suitability of this method to degrade both sunscreen agents and to eliminate estrogenic activity. - Highlights: ► Fungus T. versicolor is able to degrade totally BP3 and BP1 in few hours in a fluidised bed bioreactor. ► BP3 is not degraded under simulated sunlight. ► Glycoconjugates have been identified as the main intermediate metabolites. ► Decrease in endocrine activity was found in both photodegradation and biodegradation.

Evaluation of fungal- and photo-degradation as potential treatments for the removal of sunscreens BP3 and BP1

Energy Technology Data Exchange (ETDEWEB)

Gago-Ferrero, Pablo, E-mail: pablo.gago@idaea.csic.es [Departament de Quimica Ambiental, IDAEA-CSIC, C/ Jordi Girona 18-26, 08034 Barcelona (Spain); Badia-Fabregat, Marina, E-mail: marina.badia@uab.cat [Departament d' Enginyeria Quimica, Escola d' Enginyeria, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona (Spain); Olivares, Alba, E-mail: esalba.olivares@idaea.csic.es [Departament de Quimica Ambiental, IDAEA-CSIC, C/ Jordi Girona 18-26, 08034 Barcelona (Spain); Pina, Benjamin, E-mail: benjami.pina@idaea.csic.es [Departament de Quimica Ambiental, IDAEA-CSIC, C/ Jordi Girona 18-26, 08034 Barcelona (Spain); Blanquez, Paqui, E-mail: paqui.blanquez@uab.cat [Departament d' Enginyeria Quimica, Escola d' Enginyeria, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona (Spain); Vicent, Teresa, E-mail: teresa.vicent@uab.cat [Departament d' Enginyeria Quimica, Escola d' Enginyeria, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona (Spain); Caminal, Gloria, E-mail: gloria.caminal@uab.cat [Unitat de Biocatalisi Aplicada associada al IQAC (CSIC-UAB). Escola d' Enginyeria, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona (Spain); Diaz-Cruz, M. Silvia, E-mail: silvia.diaz@idaea.csic.es [Departament de Quimica Ambiental, IDAEA-CSIC, C/ Jordi Girona 18-26, 08034 Barcelona (Spain); and others

2012-06-15

Photodecomposition might be regarded as one of the most important abiotic factors affecting the fate of UV absorbing compounds in the environment and photocatalysis has been suggested as an effective method to degrade organic pollutants. However, UV filters transformation appears to be a complex process, barely addressed to date. The white rot fungus Trametes versicolor is considered as a promising alternative to conventional aerobic bacterial degradation, as it is able to metabolise a wide range of xenobiotics. This study focused on both degradation processes of two widely used UV filters, benzophenone-3 (BP3) and benzophenone-1 (BP1). Fungal treatment resulted in the degradation of more than 99% for both sunscreens in less than 24 h, whereas photodegradation was very inefficient, especially for BP3, which remained unaltered upon 24 h of simulated sunlight irradiation. Analysis of metabolic compounds generated showed BP1 as a minor by-product of BP3 degradation by T. versicolor while the main intermediate metabolites were glycoconjugate derivatives. BP1 and BP3 showed a weak, but significant estrogenic activity (EC50 values of 0.058 mg/L and 12.5 mg/L, respectively) when tested by recombinant yeast assay (RYA), being BP1 200-folds more estrogenic than BP3. Estrogenic activity was eliminated during T. versicolor degradation of both compounds, showing that none of the resulting metabolites possessed significant estrogenic activity at the concentrations produced. These results demonstrate the suitability of this method to degrade both sunscreen agents and to eliminate estrogenic activity. - Highlights: Black-Right-Pointing-Pointer Fungus T. versicolor is able to degrade totally BP3 and BP1 in few hours in a fluidised bed bioreactor. Black-Right-Pointing-Pointer BP3 is not degraded under simulated sunlight. Black-Right-Pointing-Pointer Glycoconjugates have been identified as the main intermediate metabolites. Black-Right-Pointing-Pointer Decrease in endocrine activity

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.

BP1 Homeoprotein Enhances Metastatic Potential in ER-negative Breast Cancer

Science.gov (United States)

Fu, Yebo; Lian, Yi; Kim, Kyung Soon; Zhang, Lei; Hindle, A. Katharine; Brody, Fred; Siegel, Robert S.; McCaffrey, Timothy A.; Fu, Sidney W.

2010-01-01

Tumor invasion and metastasis remain a major cause of mortality in breast cancer patients. It was reported that BP1, a homeobox isoform of DLX4, is overexpressed in 80% of breast cancer patients and in 100% of estrogen receptor negative (ER-) tumors. The prevalence of BP1 positive cells and the intensity of BP1 immunoreactivity increased with the extent of ductal proliferation and tumorigenesis. These findings imply that BP1 may play an important role in ER- breast cancer. We sought to determine the effects and mechanisms of BP1 on cell proliferation and metastasis using ER- Hs578T cells as a model. Cells were transfected with either pcDNA3.2 plasmid containing BP1 gene, or pcDNA3.2 vector, then selected and cloned. Overexpression of BP1 increased cell proliferation rate by 2-5 fold (p=2.0. Of those genes, 49 were up-regulated and 22 were down-regulated. Significant pathways were identified involving cell proliferation and metastasis. These data demonstrated that overexpression of BP1 significantly enhanced cell proliferation and metastatic potential in ER- Hs578T cells. Further analysis with more ER- cell lines and patient samples is warranted to establish BP1 as a therapeutic target for ER- breast cancer. PMID:20842225

Effects of Irregular Bimetallic Nanostructures on the Optical Properties of Photosystem I from Thermosynechococcus elongatus

Directory of Open Access Journals (Sweden)

Imran Ashraf

2015-07-01

Full Text Available The fluorescence of photosystem I (PSI trimers in proximity to bimetallic plasmonic nanostructures have been explored by single-molecule spectroscopy (SMS at cryogenic temperature (1.6 K. PSI serves as a model for biological multichromophore-coupled systems with high potential for biotechnological applications. Plasmonic nanostructures are fabricated by thermal annealing of thin metallic films. The fluorescence of PSI has been intensified due to the coupling with plasmonic nanostructures. Enhancement factors up to 22.9 and 5.1 are observed for individual PSI complexes coupled to Au/Au and Ag/Au samples, respectively. Additionally, a wavelength dependence of fluorescence enhancement is observed, which can be explained by the multichromophoric composition of PSI.

BP1 Homeoprotein Enhances Metastatic Potential in Er-Negative Breast Cancer

Directory of Open Access Journals (Sweden)

Yebo Fu, Yi Lian, Kyung Soon Kim, Lei Zhang, A. Katharine Hindle, Fred Brody, Robert S. Siegel, Timothy A. McCaffrey, Sidney W. Fu

2010-01-01

Full Text Available Tumor invasion and metastasis remain a major cause of mortality in breast cancer patients. It was reported that BP1, a homeobox isoform of DLX4, is overexpressed in 80% of breast cancer patients and in 100% of estrogen receptor negative (ER- tumors. The prevalence of BP1 positive cells and the intensity of BP1 immunoreactivity increased with the extent of ductal proliferation and tumorigenesis. These findings imply that BP1 may play an important role in ER- breast cancer. I sought to determine the effects and mechanisms of BP1 on cell proliferation and metastasis using ER- Hs578T cells as a model. Cells were transfected with either pcDNA3.2 plasmid containing BP1 gene, or pcDNA3.2 vector, then selected and cloned. Overexpression of BP1 increased cell proliferation rate by 2-5 fold (p<0.005, and enhanced the in vitro invasive activity by 25-65 fold (p<0.001. Microarray experiments were performed to identify differentially expressed genes when BP1 is overexpressed. The gene expression profile of the transfected cell lines were compared, resulting in 71 differentially expressed genes with a fold-change of >=2.0. Of those genes, 49 were up-regulated and 22 were down-regulated. Significant pathways were identified involving cell proliferation and metastasis. These data demonstrated that overexpression of BP1 significantly enhanced cell proliferation and metastatic potential in ER- Hs578T cells. Further analysis with more ER- cell lines and patient samples is warranted to establish BP1 as a therapeutic target.

The distribution of exocrine glands in Lepeophtheirus salmonis and Caligus elongatus (Copepoda: Caligidae)

NARCIS (Netherlands)

Bell, S.; Bron, J.E.; Sommerville, C.

2000-01-01

The morphology, function and distribution of exocrine glands of copepods have rarely been studied in detail and almost nothing is known about them in the sea lice species L. salmonis and C. elongatus. This study utilised a novel application of a light-microscopy staining technique to reveal a

Mass spectroscopic phosphoprotein mapping of Ral binding protein 1 (RalBP1/Rip1/RLIP76)

International Nuclear Information System (INIS)

Herlevsen, Mikael C.; Theodorescu, Dan

2007-01-01

RalBP1, a multifunctional protein implicated in cancer cell proliferation, radiation and chemoresistance, and ligand dependent receptor internalization, is upregulated in bladder cancer and is a downstream effector of RalB, a GTPase associated with metastasis. RalBP1 can be regulated by phosphorylation by protein kinase C (PKC). No studies have comprehensively mapped RalBP1 phosphorylation sites or whether RalB affects these. We identified 14 phosphorylation sites of RalBP1 in human bladder carcinoma UMUC-3 and embryonic kidney derived 293T cells. The phosphorylated residues are concentrated at the N-terminus. Ten of the first 100 amino acids of the primary structure were phosphorylated. Nine were serine residues, and one a threonine. We evaluated the effect of RalB overexpression on RalBP1 phosphorylation and found the largest change in phosphorylation status at S463 and S645. Further characterization of these sites will provide novel insights on RalBP1 biology, its functional relationship to RalB and possible avenues for therapeutic intervention

Nuclear Enterprises portable dose rate meter type PDR4 and external probes types BP1/1, BP8 and GP9

International Nuclear Information System (INIS)

Burgess, P.H.; Iles, W.J.

1979-08-01

The performance characteristics of Nuclear Enterprises Portable Dose Rate Meter Type PDR4 are evaluated under the headings: general description, facilities and controls, radiation characteristics, electrical characteristics, environmental characteristics, mechanical characteristics, the manual, summary of performance, and conclusions. Results of an investigation of the radiation characteristics of the external probes Type BP1/1, Type BP8, and Type GP9 are also detailed. (U.K.)

CacyBP/SIP binds ERK1/2 and affects transcriptional activity of Elk-1

International Nuclear Information System (INIS)

Kilanczyk, Ewa; Filipek, Slawomir; Jastrzebska, Beata; Filipek, Anna

2009-01-01

In this work we showed for the first time that mouse CacyBP/SIP interacts with extracellular signal regulated kinases 1 and 2 (ERK1/2). We also established that a calcium binding protein, S100A6, competes for this interaction. Moreover, the E217K mutant of CacyBP/SIP does not bind significantly to ERK1/2 although it retains the ability to interact with S100A6. Molecular modeling shows that the E217K mutation in the 189-219 CacyBP/SIP fragment markedly changes its electrostatic potential, suggesting that the binding with ERK1/2 might have an electrostatic character. We also demonstrate that CacyBP/SIP-ERK1/2 interaction inhibits phosphorylation of the Elk-1 transcription factor in vitro and in the nuclear fraction of NB2a cells. Altogether, our data suggest that the binding of CacyBP/SIP with ERK1/2 might regulate Elk-1 phosphorylation/transcriptional activity and that S100A6 might further modulate this effect via Ca 2+ -dependent interaction with CacyBP/SIP and competition with ERK1/2.

AMP-activated protein kinase phosphorylates CtBP1 and down-regulates its activity

Energy Technology Data Exchange (ETDEWEB)

Kim, Jae-Hwan; Choi, Soo-Youn; Kang, Byung-Hee; Lee, Soon-Min [National Creative Research Center for Epigenome Reprogramming Network, Departments of Biomedical Sciences and Biochemistry and Molecular Biology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Park, Hyung Soon; Kang, Gum-Yong; Bang, Joo Young [Center for Biomedical Mass Spectrometry, Diatech Korea Co., Ltd., Seoul (Korea, Republic of); Cho, Eun-Jung [National Research Laboratory for Chromatin Dynamics, College of Pharmacy, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Youn, Hong-Duk, E-mail: hdyoun@snu.ac.kr [National Creative Research Center for Epigenome Reprogramming Network, Departments of Biomedical Sciences and Biochemistry and Molecular Biology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence and Technology, Seoul National University, Seoul (Korea, Republic of)

2013-02-01

Highlights: ► AMPK phosphorylates CtBP1 on serine 158. ► AMPK-mediated phosphorylation of CtBP1 causes the ubiquitination and nuclear export of CtBP1. ► AMPK downregulates the CtBP1-mediated repression of Bax transcription. -- Abstract: CtBP is a transcriptional repressor which plays a significant role in the regulation of cell proliferation and tumor progression. It was reported that glucose withdrawal causes induction of Bax due to the dissociation of CtBP from the Bax promoter. However, the precise mechanism involved in the regulation of CtBP still remains unclear. In this study, we found that an activated AMP-activated protein kinase (AMPK) phosphorylates CtBP1 on Ser-158 upon metabolic stresses. Moreover, AMPK-mediated phosphorylation of CtBP1 (S158) attenuates the repressive function of CtBP1. We also confirmed that triggering activation of AMPK by various factors resulted in an increase of Bax gene expression. These findings provide connections of AMPK with CtBP1-mediated regulation of Bax expression for cell death under metabolic stresses.

Preliminary Geological Findings on the BP-1 Simulant

Science.gov (United States)

Stoeser, D. B.; Rickman, D. L.; Wilson, S.

2010-01-01

A waste material from an aggregate producing quarry has been used to make an inexpensive lunar simulant called BP-1. The feedstock is the Black Point lava flow in northern Arizona. Although this is part of the San Francisco volcanic field, which is also the source of the JSC-1 series feedstock, BP-1 and JSC-1 are distinct. Chemically, the Black Point flow is an amygdaloidal nepheline-bearing basalt. The amygdules are filled with secondary minerals containing opaline silica, calcium carbonate, and ferric iron minerals. X-ray diffraction (XRD) detected approximately 3% quartz, which is in line with tests done by the Kennedy Space Center Industrial Hygiene Office. Users of this material should use appropriate protective equipment. XRD also showed the presence of significant halite and some bassanite. Both are interpreted to be evaporative residues due to recycling of wash water at the quarry. The size distribution of BP-1 may be superior to some other simulants for some applications.

BP1, an Isoform of DLX4 Homeoprotein, Negatively Regulates BRCA1 in Sporadic Breast Cancer

Science.gov (United States)

Kluk, Brian J.; Fu, Yebo; Formolo, Trina A.; Zhang, Lei; Hindle, Anne K.; Man, Yan-gao; Siegel, Robert S.; Berg, Patricia E.; Deng, Chuxia; McCaffrey, Timothy A.; Fu, Sidney W.

2010-01-01

Introduction: Several lines of evidence point to an important role for BP1, an isoform of DLX4 homeobox gene, in breast carcinogenesis and progression. BRCA1 is a well-known player in the etiology of breast cancer. While familial breast cancer is often marked by BRCA1 mutation and subsequent loss of heterozygosity, sporadic breast cancers exhibit reduced expression of wild type BRCA1, and loss of BRCA1 expression may result in tumor development and progression. Methods: The Cister algorithm and Genomatix program were used to identify potential BP1 binding sites in BRCA1 gene. Real-time PCR, Western blot and immunohistochemistry analysis were performed to verify the expression of BRCA1 and BP1 in cell lines and breast cancer tissues. Double-stranded siRNA transfection was carried out for silencing BP1 expression. ChIP and EMSA were used to confirm that BP1 specifically binds to BRCA1. Results: A putative BP1 binding site was identified in the first intron of BRCA1, which was confirmed by chromatin immunoprecipiation and electrophoresis mobility shift assay. BP1 and BRCA1 expression were inversely correlated in breast cancer cell lines and tissues, suggesting that BP1 may suppress BRCA1 transcription through consensus sequence binding. Conclusions: BP1 homeoprotein represses BRCA1 expression through direct binding to its first intron, which is consistent with a previous study which identified a novel transcriptional repressor element located more than 500 base pairs into the first intron of BRCA1, suggesting that the first intron plays an important role in the negative regulation of BRCA1. Although further functional studies are necessary to confirm its repressor activity towards BRCA1, the elucidation of the role of BP1 in breast tumorigenesis holds great promise in establishing BP1 as a novel target for drug therapy. PMID:20877436

Phase 1 remedial investigation report for 200-BP-1 operable unit

International Nuclear Information System (INIS)

1993-09-01

The US Department of Energy (DOE) Hanford Site, in Washington State is organized into numerically designated operational areas including the 100, 200, 300, 400, 600, and 1100 Areas. The US Environmental Protection Agency (EPA), in November 1989 included the 200 Areas of the Hanford Site on the National Priority List (NPL) under the Comprehensive Environmental Response, Compensation and Liability Act of 1980 (CERCLA). Inclusion on the NPL initiated the remedial investigation (RD process for the 200-BP-1 operable unit. These efforts are being addressed through the Hanford Federal Facility Agreement and Consent Order (Ecology et al. 1989) which was negotiated and approved by the DOE, the EPA, and the State of Washington Department of Ecology (Ecology) in May 1989. This agreement, known as the Tri-Party Agreement, governs all CERCLA efforts at Hanford. In March of 1990, the Department of Energy, Richland Operations (DOE-RL) issued a Remedial Investigation/Feasibility Study (RI/FS) work plan (DOE-RL 1990a) for the 200-BP-1 operable unit. The work plan initiated the first phase of site characterization activities associated with the 200-BP-1 operable unit. The purpose of the 200-BP-1 operable unit RI is to gather and develop the necessary information to adequately understand the risks to human health and the environment posed by the site and to support the development and analysis of remedial alternatives during the FS. The RI analysis will, in turn, be used by Tri-Party Agreement signatories to make a risk-management-based selection of remedies for the releases of hazardous substances that have occurred from the 200-BP-1 operable unit

TopBP1-mediated DNA processing during mitosis.

Science.gov (United States)

Gallina, Irene; Christiansen, Signe Korbo; Pedersen, Rune Troelsgaard; Lisby, Michael; Oestergaard, Vibe H

2016-01-01

Maintenance of genome integrity is crucial to avoid cancer and other genetic diseases. Thus faced with DNA damage, cells mount a DNA damage response to avoid genome instability. The DNA damage response is partially inhibited during mitosis presumably to avoid erroneous processing of the segregating chromosomes. Yet our recent study shows that TopBP1-mediated DNA processing during mitosis is highly important to reduce transmission of DNA damage to daughter cells. (1) Here we provide an overview of the DNA damage response and DNA repair during mitosis. One role of TopBP1 during mitosis is to stimulate unscheduled DNA synthesis at underreplicated regions. We speculated that such genomic regions are likely to hold stalled replication forks or post-replicative gaps, which become the substrate for DNA synthesis upon entry into mitosis. Thus, we addressed whether the translesion pathways for fork restart or post-replicative gap filling are required for unscheduled DNA synthesis in mitosis. Using genetics in the avian DT40 cell line, we provide evidence that unscheduled DNA synthesis in mitosis does not require the translesion synthesis scaffold factor Rev1 or PCNA ubiquitylation at K164, which serve to recruit translesion polymerases to stalled forks. In line with this finding, translesion polymerase η foci do not colocalize with TopBP1 or FANCD2 in mitosis. Taken together, we conclude that TopBP1 promotes unscheduled DNA synthesis in mitosis independently of the examined translesion polymerases.

TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells

DEFF Research Database (Denmark)

Pedersen, Rune Troelsgaard; Kruse, Thomas; Nilsson, Jakob

2015-01-01

mitotic entry. In early mitosis, TopBP1 marks sites of and promotes unscheduled DNA synthesis. Moreover, TopBP1 is required for focus formation of the structure-selective nuclease and scaffold protein SLX4 in mitosis. Persistent TopBP1 foci transition into 53BP1 nuclear bodies (NBs) in G1 and precise...... temporal depletion of TopBP1 just before mitotic entry induced formation of 53BP1 NBs in the next cell cycle, showing that TopBP1 acts to reduce transmission of DNA damage to G1 daughter cells. Based on these results, we propose that TopBP1 maintains genome integrity in mitosis by controlling chromatin...

Phase 1 remedial investigation report for 200-BP-1 operable unit. Volume 1

Energy Technology Data Exchange (ETDEWEB)

1993-09-01

The US Department of Energy (DOE) Hanford Site, in Washington State is organized into numerically designated operational areas including the 100, 200, 300, 400, 600, and 1100 Areas. The US Environmental Protection Agency (EPA), in November 1989 included the 200 Areas of the Hanford Site on the National Priority List (NPL) under the Comprehensive Environmental Response, Compensation and Liability Act of 1980 (CERCLA). Inclusion on the NPL initiated the remedial investigation (RD process for the 200-BP-1 operable unit. These efforts are being addressed through the Hanford Federal Facility Agreement and Consent Order (Ecology et al. 1989) which was negotiated and approved by the DOE, the EPA, and the State of Washington Department of Ecology (Ecology) in May 1989. This agreement, known as the Tri-Party Agreement, governs all CERCLA efforts at Hanford. In March of 1990, the Department of Energy, Richland Operations (DOE-RL) issued a Remedial Investigation/Feasibility Study (RI/FS) work plan (DOE-RL 1990a) for the 200-BP-1 operable unit. The work plan initiated the first phase of site characterization activities associated with the 200-BP-1 operable unit. The purpose of the 200-BP-1 operable unit RI is to gather and develop the necessary information to adequately understand the risks to human health and the environment posed by the site and to support the development and analysis of remedial alternatives during the FS. The RI analysis will, in turn, be used by Tri-Party Agreement signatories to make a risk-management-based selection of remedies for the releases of hazardous substances that have occurred from the 200-BP-1 operable unit.

[Clinical significance of NS1-BP expression in esophageal squamous cell carcinoma].

Science.gov (United States)

Ren, K; Qian, D; Wang, Y W; Pang, Q S; Zhang, W C; Yuan, Z Y; Wang, P

2018-01-23

Objective: To investigate the clinical significance of NS1-BP expression in patients with esophageal squamous cell carcinoma (ESCC), and to study the roles of NS1-BP in proliferation and apoptosis of ESCC cells. Methods: A total of 98 tumor tissues and 30 adjacent normal tissues from 98 ESCC patients were used as study group and control group, and these samples were collected in Sun Yat-Sen University Cancer Center between 2002 and 2008. In addition, 46 ESCC tissues which were collected in Cancer Institute and Hospital of Tianjin Medical University were used as validation group. Expression of mucosal NS1-BP was detected by immunohistochemistry. Kaplan-Meier curve and log-rank test were used to analyze the survival rate. Multivariate Cox proportional hazard model was used to analyze the prognostic factors. Furthermore, NS1-BP was over expressed or knocked down in ESCC cells by transient transfection. Protein levels of c-Myc were detected by western blot. Cell viability and apoptosis was analyzed by MTT assay and flow cytometry. Results: Among all of tested samples, NS1-BP were down-regulated in 9 out of 30 non-tumorous normal esophageal tissues (30.0%) and 85 out of 144 ESCC tissues (59.0%), respectively, showing a statistically significant difference ( P =0.012). In the study group, three-year disease-free survival rate of NS1-BP high expression group (53.2%) was significantly higher than that of NS1-BP low expression group (27.6%; P =0.009). In the validation group, the three-year disease-free survival rates were 57.8% and 25.5% in NS1-BP high and low levels groups, respectively, showing a similar results ( P =0.016). Importantly, multivariate analyses showed that low expression of NS1-BP was an independent predictor for chemoradiotherapy sensitivity and shorter disease-free survival time in ESCC patients( P <0.05 for all). Furthermore, overexpressed NS1-BP in TE-1 cells repressed c-Myc expression, inhibited cell proliferation and promoted apoptosis. In contrast

Photosystem II Water Oxidation: Mechanism, Efficiency and Flux in Diverse Oxygenic Phototrophs

Energy Technology Data Exchange (ETDEWEB)

Dismukes, Gerard Charles [Rutgers Univ., Piscataway, NJ (United States); Ananyev, Gennady [Rutgers Univ., Piscataway, NJ (United States); Gates, Colin [Rutgers Univ., Piscataway, NJ (United States)

2018-01-09

In one year, we pursued four aims: 1) extend the VZAD model to allow analysis of PSII chlorophyll fluorescence emission as modulated by interaction with the WOC (partial success); 2) compare the solar energy conversion efficiencies of PSII-WOCs from intact cells, isolated thylakoid membranes and PSII core complexes and crystals from cyanobacterium Thermosynechococcus elongatus (collaboration with Lawrence Berkeley National Laboratory; some success after changing collaborator); 3) determine whether PSIIs can store light energy by pumping protons across the thylakoid membrane (PSII-cyclic electron flow) and how it is regulated within the green alga Chlorella ohadii (collaboration with the Hebrew University of Jerusalem; some success); and 4) genetically replace the native PSII-D1 protein subunit from a higher plant with two cyanobacterial D1 isoforms to test whether their functional advantages in growth and photoprotection can be transferred (collaboration with Rutgers University; success).

Microdeletion/microduplication of proximal 15q11.2 between BP1 and BP2: a susceptibility region for neurological dysfunction including developmental and language delay.

Science.gov (United States)

Burnside, Rachel D; Pasion, Romela; Mikhail, Fady M; Carroll, Andrew J; Robin, Nathaniel H; Youngs, Erin L; Gadi, Inder K; Keitges, Elizabeth; Jaswaney, Vikram L; Papenhausen, Peter R; Potluri, Venkateswara R; Risheg, Hiba; Rush, Brooke; Smith, Janice L; Schwartz, Stuart; Tepperberg, James H; Butler, Merlin G

2011-10-01

The proximal long arm of chromosome 15 has segmental duplications located at breakpoints BP1-BP5 that mediate the generation of NAHR-related microdeletions and microduplications. The classical Prader-Willi/Angelman syndrome deletion is flanked by either of the proximal BP1 or BP2 breakpoints and the distal BP3 breakpoint. The larger Type I deletions are flanked by BP1 and BP3 in both Prader-Willi and Angelman syndrome subjects. Those with this deletion are reported to have a more severe phenotype than individuals with either Type II deletions (BP2-BP3) or uniparental disomy 15. The BP1-BP2 region spans approximately 500 kb and contains four evolutionarily conserved genes that are not imprinted. Reports of mutations or disturbed expression of these genes appear to impact behavioral and neurological function in affected individuals. Recently, reports of deletions and duplications flanked by BP1 and BP2 suggest an association with speech and motor delays, behavioral problems, seizures, and autism. We present a large cohort of subjects with copy number alteration of BP1 to BP2 with common phenotypic features. These include autism, developmental delay, motor and language delays, and behavioral problems, which were present in both cytogenetic groups. Parental studies demonstrated phenotypically normal carriers in several instances, and mildly affected carriers in others, complicating phenotypic association and/or causality. Possible explanations for these results include reduced penetrance, altered gene dosage on a particular genetic background, or a susceptibility region as reported for other areas of the genome implicated in autism and behavior disturbances.

Metabolic engineering of cyanobacteria for photosynthetic 3-hydroxypropionic acid production from CO2 using Synechococcus elongatus PCC 7942.

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Lan, Ethan I; Chuang, Derrick S; Shen, Claire R; Lee, Annabel M; Ro, Soo Y; Liao, James C

2015-09-01

Photosynthetic conversion of CO2 to chemicals using cyanobacteria is an attractive approach for direct recycling of CO2 to useful products. 3-Hydroxypropionic acid (3 HP) is a valuable chemical for the synthesis of polymers and serves as a precursor to many other chemicals such as acrylic acid. 3 HP is naturally produced through glycerol metabolism. However, cyanobacteria do not possess pathways for synthesizing glycerol and converting glycerol to 3 HP. Furthermore, the latter pathway requires coenzyme B12, or an oxygen sensitive, coenzyme B12-independent enzyme. These characteristics present major challenges for production of 3 HP using cyanobacteria. To overcome such difficulties, we constructed two alternative pathways in Synechococcus elongatus PCC 7942: a malonyl-CoA dependent pathway and a β-alanine dependent pathway. Expression of the malonyl-CoA dependent pathway genes (malonyl-CoA reductase and malonate semialdehyde reductase) enabled S. elongatus to synthesize 3 HP to a final titer of 665 mg/L. β-Alanine dependent pathway expressing S. elongatus produced 3H P to final titer of 186 mg/L. These results demonstrated the feasibility of converting CO2 into 3 HP using cyanobacteria. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Characterization of a cancer cell line that expresses a splicing variant form of 53BP1: Separation of checkpoint and repair functions in 53BP1

International Nuclear Information System (INIS)

Iwabuchi, Kuniyoshi; Matsui, Tadashi; Hashimoto, Mitsumasa; Matsumoto, Yoshihisa; Kurihara, Takayuki; Date, Takayasu

2008-01-01

53BP1 plays important roles in checkpoint signaling and repair for DNA double-strand breaks. We found that a colon cancer cell line, SW48, expressed a splicing variant form of 53BP1, which lacks the residues corresponding to exons 10 and 11. Activation of ATM and phosphorylation of ATM and ATR targets occurred in SW48 cells in response to X-irradiation, and these X-ray-induced responses were not enhanced by expression of full-length 53BP1 in SW48 cells, indicating that this splicing variant fully activates the major checkpoint signaling in SW48 cells. In contrast, the expression of full-length 53BP1 in SW48 cells promoted the repair of X-ray-induced DNA damage, evidenced by faster disappearance of X-ray-induced γ-H2AX foci, a marker for DNA damage, and less residual chromosomal aberrations after X-irradiation. We conclude that the two major roles of 53BP1, the checkpoint signaling and repair for DNA damage, can be functionally separated

ALS mutant SOD1 interacts with G3BP1 and affects stress granule dynamics.

Science.gov (United States)

Gal, Jozsef; Kuang, Lisha; Barnett, Kelly R; Zhu, Brian Z; Shissler, Susannah C; Korotkov, Konstantin V; Hayward, Lawrence J; Kasarskis, Edward J; Zhu, Haining

2016-10-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Mutations in Cu/Zn superoxide dismutase (SOD1) are responsible for approximately 20 % of the familial ALS cases. ALS-causing SOD1 mutants display a gain-of-toxicity phenotype, but the nature of this toxicity is still not fully understood. The Ras GTPase-activating protein-binding protein G3BP1 plays a critical role in stress granule dynamics. Alterations in the dynamics of stress granules have been reported in several other forms of ALS unrelated to SOD1. To our surprise, the mutant G93A SOD1 transgenic mice exhibited pathological cytoplasmic inclusions that co-localized with G3BP1-positive granules in spinal cord motor neurons. The co-localization was also observed in fibroblast cells derived from familial ALS patient carrying SOD1 mutation L144F. Mutant SOD1, unlike wild-type SOD1, interacted with G3BP1 in an RNA-independent manner. Moreover, the interaction is specific for G3BP1 since mutant SOD1 showed little interaction with four other RNA-binding proteins implicated in ALS. The RNA-binding RRM domain of G3BP1 and two particular phenylalanine residues (F380 and F382) are critical for this interaction. Mutant SOD1 delayed the formation of G3BP1- and TIA1-positive stress granules in response to hyperosmolar shock and arsenite treatment in N2A cells. In summary, the aberrant mutant SOD1-G3BP1 interaction affects stress granule dynamics, suggesting a potential link between pathogenic SOD1 mutations and RNA metabolism alterations in ALS.

Carbon-free production of 2-deoxy-scyllo-inosose (DOI) in cyanobacterium Synechococcus elongatus PCC 7942.

Science.gov (United States)

Watanabe, Satoru; Ozawa, Hiroaki; Kato, Hiroaki; Nimura-Matsune, Kaori; Hirayama, Toshifumi; Kudo, Fumitaka; Eguchi, Tadashi; Kakinuma, Katsumi; Yoshikawa, Hirofumi

2018-01-01

Owing to their photosynthetic capabilities, there is increasing interest in utilizing cyanobacteria to convert solar energy into biomass. 2-Deoxy-scyllo-inosose (DOI) is a valuable starting material for the benzene-free synthesis of catechol and other benzenoids. DOI synthase (DOIS) is responsible for the formation of DOI from d-glucose-6-phosphate (G6P) in the biosynthesis of 2-deoxystreptamine-containing aminoglycoside antibiotics such as neomycin and butirosin. DOI fermentation using a recombinant Escherichia coli strain has been reported, although a carbon source is necessary for high-yield DOI production. We constructed DOI-producing cyanobacteria toward carbon-free and sustainable DOI production. A DOIS gene derived from the butirosin producer strain Bacillus circulans (btrC) was introduced and expressed in the cyanobacterium Synechococcus elongatus PCC 7942. We ultimately succeeded in producing 400 mg/L of DOI in S. elongatus without using a carbon source. DOI production by cyanobacteria represents a novel and efficient approach for producing benzenoids from G6P synthesized by photosynthesis.

TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells

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Pedersen, Rune Troelsgaard; Kruse, Thomas; Nilsson, Jakob

2015-01-01

Genome integrity is critically dependent on timely DNA replication and accurate chromosome segregation. Replication stress delays replication into G2/M, which in turn impairs proper chromosome segregation and inflicts DNA damage on the daughter cells. Here we show that TopBP1 forms foci upon mitotic entry. In early mitosis, TopBP1 marks sites of and promotes unscheduled DNA synthesis. Moreover, TopBP1 is required for focus formation of the structure-selective nuclease and scaffold protein SLX4 in mitosis. Persistent TopBP1 foci transition into 53BP1 nuclear bodies (NBs) in G1 and precise temporal depletion of TopBP1 just before mitotic entry induced formation of 53BP1 NBs in the next cell cycle, showing that TopBP1 acts to reduce transmission of DNA damage to G1 daughter cells. Based on these results, we propose that TopBP1 maintains genome integrity in mitosis by controlling chromatin recruitment of SLX4 and by facilitating unscheduled DNA synthesis. PMID:26283799

Age validation and variation in growth, mortality and population structure of Liza argentea and Myxus elongatus (Mugilidae) in two temperate Australian estuaries.

Science.gov (United States)

Kendall, B W; Gray, C A; Bucher, D

2009-12-01

This study investigated variation in the rates of growth and mortality, and age and fork-length (L(F)) compositions of two exploited species of Mugilidae, Liza argentea and Myxus elongatus, in two south-east Australian estuaries (Lake Macquarie and St Georges Basin). An ageing protocol was developed by counting opaque growth zones on sectioned otoliths which was validated by periodically examining the otoliths of captive-reared young-of-the-year fishes, and marginal increment analysis of wild fishes. The maximum recorded age was 17 years for L. argentea and 12 years for M. elongatus, which is greater than generally observed in other species of mugilids. Growth models of each species significantly differed between sexes and, except for male L. argentea, between estuaries. Fishes from Lake Macquarie generally had a greater mean L(F) at age than those from St Georges Basin and females of both species generally attained a greater maximum L(F) and age than males. Gillnet catches of L. argentea were of similar L(F) and age compositions in both estuaries, whereas the age composition of catches of M. elongatus in Lake Macquarie contained a greater proportion of younger fish. Estimates of total, natural and fishing mortality were greater for M. elongatus than L. argentea across both estuaries, and estimates of total mortality were greatest for both species in Lake Macquarie. The data indicate that neither species has been overfished in these estuaries.

Commensal microbiota contributes to chronic endocarditis in TAX1BP1 deficient mice.

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Satoko Nakano

Full Text Available Tax1-binding protein 1 (Tax1bp1 negatively regulates NF-κB by editing the ubiquitylation of target molecules by its catalytic partner A20. Genetically engineered TAX1BP1-deficient (KO mice develop age-dependent inflammatory constitutions in multiple organs manifested as valvulitis or dermatitis and succumb to premature death. Laser capture dissection and gene expression microarray analysis on the mitral valves of TAX1BP1-KO mice (8 and 16 week old revealed 588 gene transcription alterations from the wild type. SAA3 (serum amyloid A3, CHI3L1, HP, IL1B and SPP1/OPN were induced 1,180-, 361-, 187-, 122- and 101-fold respectively. WIF1 (Wnt inhibitory factor 1 exhibited 11-fold reduction. Intense Saa3 staining and significant I-κBα reduction were reconfirmed and massive infiltration of inflammatory lymphocytes and edema formation were seen in the area. Antibiotics-induced 'germ free' status or the additional MyD88 deficiency significantly ameliorated TAX1BP1-KO mice's inflammatory lesions. These pathological conditions, as we named 'pseudo-infective endocarditis' were boosted by the commensal microbiota who are usually harmless by their nature. This experimental outcome raises a novel mechanistic linkage between endothelial inflammation caused by the ubiquitin remodeling immune regulators and fatal cardiac dysfunction.

Using a Microfluidic Gradient Generator to Characterize BG-11 Medium for the Growth of Cyanobacteria Synechococcus elongatus PCC7942

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Chih-Chun Yang

2015-11-01

Full Text Available The photosynthetic cyanobacterium Synechococcus elongatus PCC7942 has recently gained great attention for its ability to directly convert CO2 into renewable chemicals upon genetic engineering. Thus, it is of great interest to increase the growth speed and lower the medium requirement for cultivating this cyanobacterium. The cultivation medium of Synechococcus elongatus PCC7942 has been developed, which consists of many inorganic and metal ingredients with a specific composition, known as the BG-11 medium. In this work, we analyzed the concentration effect of each ingredient and identified the absolutely essential components in BG-11 medium for cyanobacteria growth using the concentration gradient generator chip (CGGC fabricated by MEMS technology. As shown by our results, removal of the individual component sodium nitrate, potassium phosphate, or magnesium sulfate from the BG-11 medium led to severe growth inhibition of Synechococcus elongatus PCC7942. Contrary to our expectation, increasing concentration of the crucial ingredients showed either insignificant or negative impact on cell growth. Overall, standard growth could be achieved without supplementation of ethylenediaminetetraacetic acid (EDTA disodium, sodium carbonate, or sodium citrate to the culture medium. Further improvement of the CGGC-based microfluidic system based on this preliminary study may broaden its application range to analyze more complicated correlations.

Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication

International Nuclear Information System (INIS)

Kanginakudru, Sriramana; DeSmet, Marsha; Thomas, Yanique; Morgan, Iain M.; Androphy, Elliot J.

2015-01-01

The evolutionarily conserved DNA topoisomerase II beta-binding protein 1 (TopBP1) functions in DNA replication, DNA damage response, and cell survival. We analyzed the role of TopBP1 in human and bovine papillomavirus genome replication. Consistent with prior reports, TopBP1 co-localized in discrete nuclear foci and was in complex with papillomavirus E2 protein. Similar to E2, TopBP1 is recruited to the region of the viral origin of replication during G1/S and early S phase. TopBP1 knockdown increased, while over-expression decreased transient virus replication, without affecting cell cycle. Similarly, using cell lines harboring HPV-16 or HPV-31 genome, TopBP1 knockdown increased while over-expression reduced viral copy number relative to genomic DNA. We propose a model in which TopBP1 serves dual roles in viral replication: it is essential for initiation of replication yet it restricts viral copy number. - Highlights: • Protein interaction study confirmed In-situ interaction between TopBP1 and E2. • TopBP1 present at papillomavirus ori in G1/S and early S phase of cell cycle. • TopBP1 knockdown increased, over-expression reduced virus replication. • TopBP1 protein level change did not influence cell survival or cell cycle. • TopBP1 displaced from papillomavirus ori after initiation of replication

Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication

Energy Technology Data Exchange (ETDEWEB)

Kanginakudru, Sriramana, E-mail: skangina@iu.edu [Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN (United States); DeSmet, Marsha, E-mail: mdesmet@iupui.edu [Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN (United States); Thomas, Yanique, E-mail: ysthomas@umail.iu.edu [Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN (United States); Morgan, Iain M., E-mail: immorgan@vcu.edu [VCU Philips Institute for Oral Health Research, Virginia Commonwealth University, Richmond, Virginia (United States); Androphy, Elliot J., E-mail: eandro@iu.edu [Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN (United States); Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN (United States)

2015-04-15

The evolutionarily conserved DNA topoisomerase II beta-binding protein 1 (TopBP1) functions in DNA replication, DNA damage response, and cell survival. We analyzed the role of TopBP1 in human and bovine papillomavirus genome replication. Consistent with prior reports, TopBP1 co-localized in discrete nuclear foci and was in complex with papillomavirus E2 protein. Similar to E2, TopBP1 is recruited to the region of the viral origin of replication during G1/S and early S phase. TopBP1 knockdown increased, while over-expression decreased transient virus replication, without affecting cell cycle. Similarly, using cell lines harboring HPV-16 or HPV-31 genome, TopBP1 knockdown increased while over-expression reduced viral copy number relative to genomic DNA. We propose a model in which TopBP1 serves dual roles in viral replication: it is essential for initiation of replication yet it restricts viral copy number. - Highlights: • Protein interaction study confirmed In-situ interaction between TopBP1 and E2. • TopBP1 present at papillomavirus ori in G1/S and early S phase of cell cycle. • TopBP1 knockdown increased, over-expression reduced virus replication. • TopBP1 protein level change did not influence cell survival or cell cycle. • TopBP1 displaced from papillomavirus ori after initiation of replication.

Inhibition of HIF-1{alpha} activity by BP-1 ameliorates adjuvant induced arthritis in rats

Energy Technology Data Exchange (ETDEWEB)

Shankar, J. [Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago (United States); Thippegowda, P.B., E-mail: btprabha@uic.edu [Department of Pharmacology, (M/C 868), College of Medicine, University of Illinois at Chicago, 835 S. Wolcott Ave., Chicago, IL 60612 (United States); Kanum, S.A. [Department of Chemistry, Yuvaraj' s College, University of Mysore, Mysore (India)

2009-09-18

Rheumatoid arthritis (RA) is a chronic inflammatory, angiogenic disease. Inflamed synovitis is a hallmark of RA which is hypoxic in nature. Vascular endothelial growth factor (VEGF), one of the key regulators of angiogenesis, is overexpressed in the pathogenesis of RA. VEGF expression is regulated by hypoxia-inducible factor-1{alpha} (HIF-1{alpha}), a master regulator of homeostasis which plays a pivotal role in hypoxia-induced angiogenesis. In this study we show that synthetic benzophenone analogue, 2-benzoyl-phenoxy acetamide (BP-1) can act as a novel anti-arthritic agent in an experimental adjuvant induced arthritis (AIA) rat model by targeting VEGF and HIF-1{alpha}. BP-1 administered hypoxic endothelial cells and arthritic animals clearly showed down regulation of VEGF expression. Further, BP-1 inhibits nuclear translocation of HIF-1{alpha}, which in turn suppresses transcription of the VEGF gene. These results suggest a further possible clinical application of the BP-1 derivative as an anti-arthritic agent in association with conventional chemotherapeutic agents.

RanBP3 influences interactions between CRM1 and its nuclear protein export substrates

OpenAIRE

Englmeier, Ludwig; Fornerod, Maarten; Bischoff, F. Ralf; Petosa, Carlo; Mattaj, Iain W.; Kutay, Ulrike

2001-01-01

We investigated the role of RanBP3, a nuclear member of the Ran-binding protein 1 family, in CRM1-mediated protein export in higher eukaryotes. RanBP3 interacts directly with CRM1 and also forms a trimeric complex with CRM1 and RanGTP. However, RanBP3 does not bind to CRM1 like an export substrate. Instead, it can stabilize CRM1–export substrate interaction. Nuclear RanBP3 stimulates CRM1-dependent protein export in permeabilized cells. These data indicate that RanBP3 functions by a novel mec...

Integration of DNA barcoding for the initial recordings of Lessepsian fishes: a case study of the Indo-Pacific slender ponyfish Equulites elongatus.

Science.gov (United States)

Sakinan, S; Karahan, A; Ok, M

2017-03-01

In this study, the DNA barcode of a regional Lessepsian sighting of the slender ponyfish Equulites elongatus is integrated with morphometric and meristic descriptors as a case study to address further identification problems in the Mediterranean Sea. The study also aims to contribute to the regional mitochondrial cytochrome oxidase I information pool, to support other potential uses. The initial sighting of E. elongatus from the north-eastern Mediterranean coast of Turkey is provided from a trawl survey on 3 June 2015, where 76 specimens were captured during a 15 min tow. © 2016 The Fisheries Society of the British Isles.

Hsp70 cochaperones HspBP1 and BAG-1M differentially regulate steroid hormone receptor function.

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Regina T Knapp

Full Text Available Hsp70 binding protein 1 (HspBP1 and Bcl2-associated athanogene 1 (BAG-1, the functional orthologous nucleotide exchange factors of the heat shock protein 70 kilodalton (Hsc70/Hsp70 chaperones, catalyze the release of ADP from Hsp70 while inducing different conformational changes of the ATPase domain of Hsp70. An appropriate exchange rate of ADP/ATP is crucial for chaperone-dependent protein folding processes. Among Hsp70 client proteins are steroid receptors such as the glucocorticoid receptor (GR, the mineralocorticoid receptor (MR, and the androgen receptor (AR. BAG-1 diversely affects steroid receptor activity, while to date the influence of HspBP1 on steroid receptor function is mostly unknown. Here, we compared the influence of HspBP1 and BAG-1M on Hsp70-mediated steroid receptor folding complexes and steroid receptor activity. Coimmunoprecipitation studies indicated preferential binding of Hsp40 and the steroid receptors to BAG-1M as compared to HspBP1. Furthermore, Hsp70 binding to the ligand-binding domain of GR was reduced in the presence of HspBP1 but not in the presence of BAG-1M as shown by pull-down assays. Reporter gene experiments revealed an inhibitory effect on GR, MR, and AR at a wide range of HspBP1 protein levels and at hormone concentrations at or approaching saturation. BAG-1M exhibited a transition from stimulatory effects at low BAG-1M levels to inhibitory effects at higher BAG-1M levels. Overall, BAG-1M and HspBP1 had differential impacts on the dynamic composition of steroid receptor folding complexes and on receptor function with important implications for steroid receptor physiology.

Anatomy and systematics of Anodontites Elongatus (Swainson from Amazon and Parana Basins, Brazil (Mollusca, Bivalvia, Unionoida, Mycetopodidae

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Luiz Ricardo L Simone

1997-12-01

Full Text Available The anatomy of Anodontiies elongatus (Swainson, 1823, a rare species restricted to the Amazon and Parana Basins, is described by first time, showing a group of conchological and anatomical characters exclusive of this species that may be analyzed to identify it. Diagnosis of A. elongatus: shell long antero-posteriorly, umbones prominent, periostracum opaque and smooth, two posterior radial striae; middle fold of mantle edge veiy tall; gill long antero-posteriorly and short dorso-ventrally, extending about a half of it total length beyond visceral mass; palps proportionally small, several furrows in its outer surface; stomach without esophageal transversal ridjp, dorsal hood and gastric shield poorly developed, major typhlosole entering in ddd , posterior pouch of sa³ very-long; style sac reduced, without crystalline style; distal region of intestine and rectum with a well developed typhlosole, "T" in section, other intestinal regions without folds; gonad gonochoristic.

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.

Two new species of the Liolaemus elongatus-kriegi complex (Iguania, Liolaemidae) from Andean highlands of southern Chile

Science.gov (United States)

Troncoso-Palacios, Jaime; Díaz, Hugo A.; Esquerré, Damien; Urra, Felix A.

2015-01-01

Abstract The elongatus-kriegi complex is one of the most diverse clades of the Liolaemus (sensu stricto) subgenus of lizards. There are currently 29 species recognized in this group distributed between Chile and Argentina. Based on molecular evidence, there seem to be five main clades nested within this complex: the elongatus, leopardinus, kriegi, petrophilus and punmahuida clades. Liolaemus buergeri and Liolaemus kriegi, both of the kriegi clade, were believed to inhabit the surroundings of the Laja Lagoon, in the Biobío Region of Chile. Moreover, this Chilean population of Liolaemus kriegi was recently recognized as an undescribed taxon called “Liolaemus sp. A” based on molecular phylogenetics. In this work, we studied these two populations of the Laja Lagoon and provided the morphological diagnosis to describe them as two new species: Liolaemus scorialis sp. n. and Liolaemus zabalai sp. n., previously considered Liolaemus buergeri and “Liolaemus kriegi/Liolaemus sp. A” respectively. Additionally, we identified another population of Liolaemus scorialis in the vicinity of La Mula Lagoon in the Araucanía Region of Chile. Liolaemus scorialis differs from almost all of the species of the elongatus-kriegi complex by its considerably smaller size. Nevertheless, without molecular data we cannot assign it to any particular subclade. Liolaemus zabalai belongs to the kriegi clade based on published molecular phylogenies. Finally, we provide some natural history data on both species and we document for the first time the presence of Liolaemus neuquensis in Chile from a museum specimen from La Mula Lagoon. PMID:25987873

Correlation of expression of BP1, a homeobox gene, with estrogen receptor status in breast cancer

International Nuclear Information System (INIS)

Fu, Sidney W; Poola, Indira; Stephan, Dietrich A; Berg, Patricia E; Schwartz, Arnold; Stevenson, Holly; Pinzone, Joseph J; Davenport, Gregory J; Orenstein, Jan M; Gutierrez, Peter; Simmens, Samuel J; Abraham, Jessy

2003-01-01

BP1 is a novel homeobox gene cloned in our laboratory. Our previous studies in leukemia demonstrated that BP1 has oncogenic properties, including as a modulator of cell survival. Here BP1 expression was examined in breast cancer, and the relationship between BP1 expression and clinicopathological data was determined. Total RNA was isolated from cell lines, tumors, and matched normal adjacent tissue or tissue from autopsy. Reverse transcription polymerase chain reaction was performed to evaluate BP1 expression. Statistical analysis was accomplished with SAS. Analysis of 46 invasive ductal breast tumors demonstrated BP1 expression in 80% of them, compared with a lack of expression in six normal breast tissues and low-level expression in one normal breast tissue. Remarkably, 100% of tumors that were negative for the estrogen receptor (ER) were BP1-positive, whereas 73% of ER-positive tumors expressed BP1 (P = 0.03). BP1 expression was also associated with race: 89% of the tumors of African American women were BP1-positive, whereas 57% of those from Caucasian women expressed BP1 (P = 0.04). However, there was no significant difference in BP1 expression between grades I, II, and III tumors. Interestingly, BP1 mRNA expression was correlated with the ability of malignant cell lines to cause breast cancer in mice. Because BP1 is expressed abnormally in breast tumors, it could provide a useful target for therapy, particularly in patients with ER-negative tumors. The frequent expression of BP1 in all tumor grades suggests that activation of BP1 is an early event

G3BP1, G3BP2 and CAPRIN1 are required for translation of interferon stimulated mRNAs and are targeted by a dengue virus non-coding RNA.

Science.gov (United States)

Bidet, Katell; Dadlani, Dhivya; Garcia-Blanco, Mariano A

2014-07-01

Viral RNA-host protein interactions are critical for replication of flaviviruses, a genus of positive-strand RNA viruses comprising major vector-borne human pathogens including dengue viruses (DENV). We examined three conserved host RNA-binding proteins (RBPs) G3BP1, G3BP2 and CAPRIN1 in dengue virus (DENV-2) infection and found them to be novel regulators of the interferon (IFN) response against DENV-2. The three RBPs were required for the accumulation of the protein products of several interferon stimulated genes (ISGs), and for efficient translation of PKR and IFITM2 mRNAs. This identifies G3BP1, G3BP2 and CAPRIN1 as novel regulators of the antiviral state. Their antiviral activity was antagonized by the abundant DENV-2 non-coding subgenomic flaviviral RNA (sfRNA), which bound to G3BP1, G3BP2 and CAPRIN1, inhibited their activity and lead to profound inhibition of ISG mRNA translation. This work describes a new and unexpected level of regulation for interferon stimulated gene expression and presents the first mechanism of action for an sfRNA as a molecular sponge of anti-viral effectors in human cells.

G3BP1, G3BP2 and CAPRIN1 are required for translation of interferon stimulated mRNAs and are targeted by a dengue virus non-coding RNA.

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Katell Bidet

2014-07-01

Full Text Available Viral RNA-host protein interactions are critical for replication of flaviviruses, a genus of positive-strand RNA viruses comprising major vector-borne human pathogens including dengue viruses (DENV. We examined three conserved host RNA-binding proteins (RBPs G3BP1, G3BP2 and CAPRIN1 in dengue virus (DENV-2 infection and found them to be novel regulators of the interferon (IFN response against DENV-2. The three RBPs were required for the accumulation of the protein products of several interferon stimulated genes (ISGs, and for efficient translation of PKR and IFITM2 mRNAs. This identifies G3BP1, G3BP2 and CAPRIN1 as novel regulators of the antiviral state. Their antiviral activity was antagonized by the abundant DENV-2 non-coding subgenomic flaviviral RNA (sfRNA, which bound to G3BP1, G3BP2 and CAPRIN1, inhibited their activity and lead to profound inhibition of ISG mRNA translation. This work describes a new and unexpected level of regulation for interferon stimulated gene expression and presents the first mechanism of action for an sfRNA as a molecular sponge of anti-viral effectors in human cells.

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

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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.

Lamin A/C-dependent interaction with 53BP1 promotes cellular responses to DNA damage

DEFF Research Database (Denmark)

Gibbs-Seymour, Ian; Markiewicz, Ewa; Bekker-Jensen, Simon

2015-01-01

Lamins A/C have been implicated in DNA damage response pathways. We show that the DNA repair protein 53BP1 is a lamin A/C binding protein. In undamaged human dermal fibroblasts (HDF), 53BP1 is a nucleoskeleton protein. 53BP1 binds to lamins A/C via its Tudor domain, and this is abrogated by DNA...... damage. Lamins A/C regulate 53BP1 levels and consequently lamin A/C-null HDF display a 53BP1 null-like phenotype. Our data favour a model in which lamins A/C maintain a nucleoplasmic pool of 53BP1 in order to facilitate its rapid recruitment to sites of DNA damage and could explain why an absence...

FDG goes BP

International Nuclear Information System (INIS)

Chan, J.G.

2000-01-01

Full text: A monograph for Fluorodeoxyglucose F-18 Injection (FDG) was first released in Supplement 1 of the United States Pharmacopoeia 1990 (USP 90) on 1 November 1989 to become effective on 1 January 1990. As this was the only monograph available until recently it served as the applicable standard to be followed. The Therapeutic Goods Act states that the British Pharmacopoeia (BP) is the precedent to be followed in Australia and implies that if a monograph exists for a finished product then this needs to be applied to achieve a certain standard of quality. If the monograph does not exist in the BP then other pharmacopoeia monographs can be sourced starting with the European Pharmacopoeia (Ph Eur) then the USP. A monograph for FDG first appeared in the Ph Eur in a 1999 Supplement (effective 1 January 1999 and now included in the Ph Eur 2000) and then in the BP 1999 (effective 1 December 1999). The Commonwealth Government Gazette (Notice 48, 1/12/99) published that the BP 99 was adopted on the 1st December 1999. Since then manufacturers have been required to comply with the monograph for FDG in the BP 99. This presentation looks at the content of the BP 99 monograph and compares it with that in the USP. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

Structural basis for the differential effects of CaBP1 and calmodulin on CaV1.2 calcium-dependent inactivation

Science.gov (United States)

Findeisen, Felix; Minor, Daniel L.

2010-01-01

Calcium-binding protein 1 (CaBP1), a calmodulin (CaM) homolog, endows certain voltage-gated calcium channels (CaVs) with unusual properties. CaBP1 inhibits CaV1.2 calcium-dependent inactivation (CDI) and introduces calcium-dependent facilitation (CDF). Here, we show that the ability of CaBP1 to inhibit CaV1.2 CDI and induce CDF arises from interaction between the CaBP1 N-lobe and interlobe linker residue Glu94. Unlike CaM, where functional EF hands are essential for channel modulation, CDI inhibition does not require functional CaBP1 EF-hands. Furthermore, CaBP1-mediated CDF has different molecular requirements than CaM-mediated CDF. Overall, the data show that CaBP1 comprises two structural modules having separate functions: similar to CaM, the CaBP1 C-lobe serves as a high-affinity anchor that binds the CaV1.2 IQ domain at a site that overlaps with the Ca2+/CaM C-lobe site, whereas the N-lobe/linker module houses the elements required for channel modulation. Discovery of this division provides the framework for understanding how CaBP1 regulates CaVs. PMID:21134641

Structural basis for the differential effects of CaBP1 and calmodulin on Ca(V)1.2 calcium-dependent inactivation.

Science.gov (United States)

Findeisen, Felix; Minor, Daniel L

2010-12-08

Calcium-binding protein 1 (CaBP1), a calmodulin (CaM) homolog, endows certain voltage-gated calcium channels (Ca(V)s) with unusual properties. CaBP1 inhibits Ca(V)1.2 calcium-dependent inactivation (CDI) and introduces calcium-dependent facilitation (CDF). Here, we show that the ability of CaBP1 to inhibit Ca(V)1.2 CDI and induce CDF arises from interaction between the CaBP1 N-lobe and interlobe linker residue Glu94. Unlike CaM, where functional EF hands are essential for channel modulation, CDI inhibition does not require functional CaBP1 EF hands. Furthermore, CaBP1-mediated CDF has different molecular requirements than CaM-mediated CDF. Overall, the data show that CaBP1 comprises two structural modules having separate functions: similar to CaM, the CaBP1 C-lobe serves as a high-affinity anchor that binds the Ca(V)1.2 IQ domain at a site that overlaps with the Ca²+/CaM C-lobe site, whereas the N-lobe/linker module houses the elements required for channel modulation. Discovery of this division provides the framework for understanding how CaBP1 regulates Ca(V)s. Copyright © 2010 Elsevier Ltd. All rights reserved.

BRCA1-associated exclusion of 53BP1 from DNA damage sites underlies temporal control of DNA repair

Science.gov (United States)

Chapman, J. Ross; Sossick, Alex J.; Boulton, Simon J.; Jackson, Stephen P.

2012-01-01

Summary Following irradiation, numerous DNA-damage-responsive proteins rapidly redistribute into microscopically visible subnuclear aggregates, termed ionising-radiation-induced foci (IRIF). How the enrichment of proteins on damaged chromatin actually relates to DNA repair remains unclear. Here, we use super-resolution microscopy to examine the spatial distribution of BRCA1 and 53BP1 proteins within single IRIF at subdiffraction-limit resolution, yielding an unprecedented increase in detail that was not previously apparent by conventional microscopy. Consistent with a role for 53BP1 in promoting DNA double-strand break repair by non-homologous end joining, 53BP1 enrichment in IRIF is most prominent in the G0/G1 cell cycle phases, where it is enriched in dense globular structures. By contrast, as cells transition through S phase, the recruitment of BRCA1 into the core of IRIF is associated with an exclusion of 53BP1 to the focal periphery, leading to an overall reduction of 53BP1 occupancy at DNA damage sites. Our data suggest that the BRCA1-associated IRIF core corresponds to chromatin regions associated with repair by homologous recombination, and the enrichment of BRCA1 in IRIF represents a temporal switch in the DNA repair program. We propose that BRCA1 antagonises 53BP1-dependent DNA repair in S phase by inhibiting its interaction with chromatin proximal to damage sites. Furthermore, the genomic instability exhibited by BRCA1-deficient cells might result from a failure to efficiently exclude 53BP1 from such regions during S phase. PMID:22553214

Mutant p53 perturbs DNA replication checkpoint control through TopBP1 and Treslin.

Science.gov (United States)

Liu, Kang; Lin, Fang-Tsyr; Graves, Joshua D; Lee, Yu-Ju; Lin, Weei-Chin

2017-05-09

Accumulating evidence supports the gain-of-function of mutant forms of p53 (mutp53s). However, whether mutp53 directly perturbs the DNA replication checkpoint remains unclear. Previously, we have demonstrated that TopBP1 forms a complex with mutp53s and mediates their gain-of-function through NF-Y and p63/p73. Akt phosphorylates TopBP1 and induces its oligomerization, which inhibits its ATR-activating function. Here we show that various contact and conformational mutp53s bypass Akt to induce TopBP1 oligomerization and attenuate ATR checkpoint response during replication stress. The effect on ATR response caused by mutp53 can be exploited in a synthetic lethality strategy, as depletion of another ATR activator, DNA2, in mutp53-R273H-expressing cancer cells renders cells hypersensitive to cisplatin. Expression of mutp53-R273H also makes cancer cells more sensitive to DNA2 depletion or DNA2 inhibitors. In addition to ATR-activating function during replication stress, TopBP1 interacts with Treslin in a Cdk-dependent manner to initiate DNA replication during normal growth. We find that mutp53 also interferes with TopBP1 replication function. Several contact, but not conformational, mutp53s enhance the interaction between TopBP1 and Treslin and promote DNA replication despite the presence of a Cdk2 inhibitor. Together, these data uncover two distinct mechanisms by which mutp53 enhances DNA replication: ( i ) Both contact and conformational mutp53s can bind TopBP1 and attenuate the checkpoint response to replication stress, and ( ii ) during normal growth, contact (but not conformational) mutp53s can override the Cdk2 requirement to promote replication by facilitating the TopBP1/Treslin interaction.

Seasonal changes in food quantity and quality of the common North Sea copepods Temora longicornis and Pseudocalanus elongatus: a bioassay approach

DEFF Research Database (Denmark)

Koski, Marja; Dutz, Jörg; Klein Breteler, W.

2010-01-01

We evaluated the food quantity and quality over a seasonal cycle for the development and egg production of the common North Sea copepods Temora longicornis and Pseudocalanus elongatus, using a bioassay approach. Seston was sampled from December to October from a well-mixed water column of the Mar......We evaluated the food quantity and quality over a seasonal cycle for the development and egg production of the common North Sea copepods Temora longicornis and Pseudocalanus elongatus, using a bioassay approach. Seston was sampled from December to October from a well-mixed water column...... with the seston from the spring bloom in March-April. The juveniles of both species were able to complete their development only in spring experiments. A multiple regression analyses and comparison to a good-quality standard food of the same concentration suggested that, in an annual scale, the egg production...

TopBP1/Dpb11 binds DNA anaphase bridges to prevent genome instability.

Science.gov (United States)

Germann, Susanne M; Schramke, Vera; Pedersen, Rune Troelsgaard; Gallina, Irene; Eckert-Boulet, Nadine; Oestergaard, Vibe H; Lisby, Michael

2014-01-06

DNA anaphase bridges are a potential source of genome instability that may lead to chromosome breakage or nondisjunction during mitosis. Two classes of anaphase bridges can be distinguished: DAPI-positive chromatin bridges and DAPI-negative ultrafine DNA bridges (UFBs). Here, we establish budding yeast Saccharomyces cerevisiae and the avian DT40 cell line as model systems for studying DNA anaphase bridges and show that TopBP1/Dpb11 plays an evolutionarily conserved role in their metabolism. Together with the single-stranded DNA binding protein RPA, TopBP1/Dpb11 binds to UFBs, and depletion of TopBP1/Dpb11 led to an accumulation of chromatin bridges. Importantly, the NoCut checkpoint that delays progression from anaphase to abscission in yeast was activated by both UFBs and chromatin bridges independently of Dpb11, and disruption of the NoCut checkpoint in Dpb11-depleted cells led to genome instability. In conclusion, we propose that TopBP1/Dpb11 prevents accumulation of anaphase bridges via stimulation of the Mec1/ATR kinase and suppression of homologous recombination.

Quantitative analysis of the interplay between hsc70 and its co-chaperone HspBP1

Directory of Open Access Journals (Sweden)

Hicham Mahboubi

2015-12-01

Full Text Available Background. Chaperones and their co-factors are components of a cellular network; they collaborate to maintain proteostasis under normal and harmful conditions. In particular, hsp70 family members and their co-chaperones are essential to repair damaged proteins. Co-chaperones are present in different subcellular compartments, where they modulate chaperone activities.Methods and Results. Our studies assessed the relationship between hsc70 and its co-factor HspBP1 in human cancer cells. HspBP1 promotes nucleotide exchange on hsc70, but has also chaperone-independent functions. We characterized the interplay between hsc70 and HspBP1 by quantitative confocal microscopy combined with automated image analyses and statistical evaluation. Stress and the recovery from insult changed significantly the subcellular distribution of hsc70, but had little effect on HspBP1. Single-cell measurements and regression analysis revealed that the links between the chaperone and its co-factor relied on (i the physiological state of the cell and (ii the subcellular compartment. As such, we identified a linear relationship and strong correlation between hsc70 and HspBP1 distribution in control and heat-shocked cells; this correlation changed in a compartment-specific fashion during the recovery from stress. Furthermore, we uncovered significant stress-induced changes in the colocalization between hsc70 and HspBP1 in the nucleus and cytoplasm.Discussion. Our quantitative approach defined novel properties of the co-chaperone HspBP1 as they relate to its interplay with hsc70. We propose that changes in cell physiology promote chaperone redistribution and thereby stimulate chaperone-independent functions of HspBP1.

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.

BP reactivity to public speaking in stage 1 hypertension: influence of different task scenarios.

Science.gov (United States)

Palatini, Paolo; Bratti, Paolo; Palomba, Daniela; Bonso, Elisa; Saladini, Francesca; Benetti, Elisabetta; Casiglia, Edoardo

2011-10-01

To investigate the blood pressure (BP) reaction to public speaking performed according to different emotionally distressing scenarios in stage 1 hypertension. METHODS. We assessed 64 hypertensive and 30 normotensive subjects. They performed three speech tasks with neutral, anger and anxiety scenarios. BP was assessed with the Finometer beat-to-beat non-invasive recording system throughout the test procedure. For all types of speech, the systolic BP response was greater in the hypertensive than the normotensive subjects (all p public speaking is increased in stage 1 hypertension. A speech with anxiety or anger scenario elicits a greater diastolic BP reaction than tasks with neutral content.

TopBP1/Dpb11 binds DNA anaphase bridges to prevent genome instability

DEFF Research Database (Denmark)

Germann, Susanne Manuela; Schramke, Vera; Pedersen, Rune Troelsgaard

2014-01-01

yeast Saccharomyces cerevisiae and the avian DT40 cell line as model systems for studying DNA anaphase bridges and show that TopBP1/Dpb11 plays an evolutionarily conserved role in their metabolism. Together with the single-stranded DNA binding protein RPA, TopBP1/Dpb11 binds to UFBs, and depletion...

A new species of Leporinus Agassiz, 1829 from the upper Rio Paraná basin (Characiformes, Anostomidae with redescription of L. elongatus Valenciennes, 1850 and L. obtusidens (Valenciennes, 1837

Directory of Open Access Journals (Sweden)

Heraldo A. Britski

2012-01-01

Full Text Available Leporinus obtusidens Valenciennes, 1837 and L. elongatus Valenciennes, 1850 are redescribed based on the type specimens, including those of their junior synonyms, and recently collected specimens. Leporinus obtusidens is considered to be widespread, occuring in the river drainages of La Plata, São Francisco, and Parnaíba. Leporinus aguapeiensis Campos, 1945, described from the upper Rio Paraná, and L. silvestrii Boulenger, 1902, described from the Rio Paraguay, are considered junior synonyms of L. obtusidens. Leporinus elongatus is endemic to the Rio Jequitinhonha and Rio Pardo, two eastern Brazilian river basins, and the locality cited for the lectotype, Rio São Fransico, likely to be erroneous. Leporinus crassilabris Borodin, 1929, and L. crassilabris breviceps Borodin, 1929, both described from the Rio Jequitinhonha, are considered junior synynoms of L. elongatus. A new species of Leporinus, endemic to the upper Rio Paraná, very similar and sometimes mistaken with L. obtusidens, is formally described. In addition, comments on Leporinus pachyurus Valenciennes, 1850 and on L. bimaculatus Castelnau, 1855 are provided, and a lectotype for L. bimaculatus is selected.

A cell cycle-dependent regulatory circuit composed of 53BP1-RIF1 and BRCA1-CtIP controls DNA repair pathway choice.

Science.gov (United States)

Escribano-Díaz, Cristina; Orthwein, Alexandre; Fradet-Turcotte, Amélie; Xing, Mengtan; Young, Jordan T F; Tkáč, Ján; Cook, Michael A; Rosebrock, Adam P; Munro, Meagan; Canny, Marella D; Xu, Dongyi; Durocher, Daniel

2013-03-07

DNA double-strand break (DSB) repair pathway choice is governed by the opposing activities of 53BP1 and BRCA1. 53BP1 stimulates nonhomologous end joining (NHEJ), whereas BRCA1 promotes end resection and homologous recombination (HR). Here we show that 53BP1 is an inhibitor of BRCA1 accumulation at DSB sites, specifically in the G1 phase of the cell cycle. ATM-dependent phosphorylation of 53BP1 physically recruits RIF1 to DSB sites, and we identify RIF1 as the critical effector of 53BP1 during DSB repair. Remarkably, RIF1 accumulation at DSB sites is strongly antagonized by BRCA1 and its interacting partner CtIP. Lastly, we show that depletion of RIF1 is able to restore end resection and RAD51 loading in BRCA1-depleted cells. This work therefore identifies a cell cycle-regulated circuit, underpinned by RIF1 and BRCA1, that governs DSB repair pathway choice to ensure that NHEJ dominates in G1 and HR is favored from S phase onward. Copyright © 2013 Elsevier Inc. All rights reserved.

Spatial genetic structure and mitochondrial DNA phylogeography of Argentinean populations of the grasshopper Dichroplus elongatus.

Directory of Open Access Journals (Sweden)

Natalia Rosetti

Full Text Available Many grasshopper species are considered of agronomical importance because they cause damage to pastures and crops. Comprehension of pest population dynamics requires a clear understanding of the genetic diversity and spatial structure of populations. In this study we report on patterns of genetic variation in the South American grasshopper Dichroplus elongatus which is an agricultural pest of crops and forage grasses of great economic significance in Argentina. We use Direct Amplification of Minisatellite Regions (DAMD and partial sequences of the cytochrome oxydase 1 (COI mitochondrial gene to investigate intraspecific structure, demographic history and gene flow patterns in twenty Argentinean populations of this species belonging to different geographic and biogeographic regions. DAMD data suggest that, although genetic drift and migration occur within and between populations, measurable relatedness among neighbouring populations declines with distance and dispersal over distances greater than 200 km is not typical, whereas effective gene flow may occur for populations separated by less than 100 km. Landscape analysis was useful to detect genetic discontinuities associated with environmental heterogeneity reflecting the changing agroecosystem. The COI results indicate the existence of strong genetic differentiation between two groups of populations located at both margins of the Paraná River which became separated during climate oscillations of the Middle Pleistocene, suggesting a significant restriction in effective dispersion mediated by females and large scale geographic differentiation. The number of migrants between populations estimated through mitochondrial and DAMD markers suggest that gene flow is low prompting a non-homogeneous spatial structure and justifying the variation through space. Moreover, the genetic analysis of both markers allows us to conclude that males appear to disperse more than females, reducing the chance of the

Morphology, chemistry and function of the postpharyngeal gland in the South American digger wasps Trachypus boharti and Trachypus elongatus.

Directory of Open Access Journals (Sweden)

Gudrun Herzner

Full Text Available Microbes pose severe threats to animals as competitors or pathogens and strongly affect the evolution of life history traits like parental care. Females of the European beewolf Philanthus triangulum, a solitary digger wasp, provision their offspring with paralyzed honeybees and embalm them with the secretion from large postpharyngeal glands (PPG that contain mainly unsaturated hydrocarbons. This coating changes the physico-chemical properties of the prey surface, causes a reduction of water condensation and retards growth of mold fungi. Here we examined the closely related South American genus Trachypus, which shows a life-history similar to Philanthus. We investigated whether Trachypus spp. also possess PPGs and embalm larval provisions. Using histological methods and 3D reconstructions we show that Trachypus boharti and T. elongatus possess PPGs that are similar to P. triangulum but somewhat smaller. The ultrastructure of the gland epithelium suggests that the gland content is at least partly sequestered from the hemolymph. Chemical analyses using gas chromatography / mass spectrometry revealed that both the cuticle and PPGs of Trachypus contain mainly unsaturated long-chain hydrocarbons. The gland of T. boharti additionally contains long-chain ketones. The hydrocarbons from the PPG of T. elongatus occurred on prey bees excavated from nests in the field but not on conspecific control bees. While the embalming only slightly elevated the amount of hydrocarbons on prey bees, the proportion of unsaturated hydrocarbons, which is crucial for the antifungal effect, was significantly increased. The Trachypus species under study possess PPGs that are very similar to the PPG of P. triangulum with regard to morphology, ultrastructure and chemistry. Moreover, we provide clear evidence that T. elongatus females embalm their prey, presumably as a means of prey preservation. The observed differences among Trachypus and Philanthus in gland size and prey

Impact of histone H4 lysine 20 methylation on 53BP1 responses to chromosomal double strand breaks.

Directory of Open Access Journals (Sweden)

Andrea J Hartlerode

Full Text Available Recruitment of 53BP1 to chromatin flanking double strand breaks (DSBs requires γH2AX/MDC1/RNF8-dependent ubiquitination of chromatin and interaction of 53BP1 with histone H4 methylated on lysine 20 (H4K20me. Several histone methyltransferases have been implicated in 53BP1 recruitment, but their quantitative contributions to the 53BP1 response are unclear. We have developed a multi-photon laser (MPL system to target DSBs to subfemtoliter nuclear volumes and used this to mathematically model DSB response kinetics of MDC1 and of 53BP1. In contrast to MDC1, which revealed first order kinetics, the 53BP1 MPL-DSB response is best fitted by a Gompertz growth function. The 53BP1 MPL response shows the expected dependency on MDC1 and RNF8. We determined the impact of altered H4K20 methylation on 53BP1 MPL response kinetics in mouse embryonic fibroblasts (MEFs lacking key H4K20 histone methyltransferases. This revealed no major requirement for the known H4K20 dimethylases Suv4-20h1 and Suv4-20h2 in 53BP1 recruitment or DSB repair function, but a key role for the H4K20 monomethylase, PR-SET7. The histone methyltransferase MMSET/WHSC1 has recently been implicated in 53BP1 DSB recruitment. We found that WHSC1 homozygous mutant MEFs reveal an alteration in balance of H4K20 methylation patterns; however, 53BP1 DSB responses in these cells appear normal.

ATM signaling and 53BP1

International Nuclear Information System (INIS)

Zgheib, Omar; Huyen, Yentram; DiTullio, Richard A.; Snyder, Andrew; Venere, Monica; Stavridi, Elena S.; Halazonetis, Thanos D.

2005-01-01

The ATM (mutated in Ataxia-Telangiectasia) protein kinase is an important player in signaling the presence of DNA double strand breaks (DSBs) in higher eukaryotes. Recent studies suggest that ATM monitors the presence of DNA DSBs indirectly, through DNA DSB-induced changes in chromatin structure. One of the proteins that sense these chromatin structure changes is 53BP1, a DNA damage checkpoint protein conserved in all eukaryotes and the putative ortholog of the S. cerevisiae RAD9 protein. We review here the mechanisms by which ATM is activated in response to DNA DSBs, as well as key ATM substrates that control cell cycle progression, apoptosis and DNA repair

53BP1 loss suppresses the radiosensitizing effect of icotinib hydrochloride in colorectal cancer cells.

Science.gov (United States)

Huang, Ai; Yao, Jing; Liu, Tao; Lin, Zhenyu; Zhang, Sheng; Zhang, Tao; Ma, Hong

2018-04-01

This study aimed to investigate the influence of the expression of P53-binding protein 1 (53BP1), a key component in DNA damage repair pathways, on the radiosensitizing effect of icotinib hydrochloride in colorectal cancer and to elucidate the mechanisms underlying this influence. Real-time RT-PCR and Western blotting were performed to verify the gene-knockout effect of 53BP1 small hairpin RNA (ShRNA), and colony formation assay was employed to investigate the influence of 53BP1 downregulation on the radiosensitizing effect of icotinib hydrochloride in HCT116 cells. Cell apoptosis, cell cycle distributions, and histone H2AX (γ-H2AX) fluorescence foci after 53BP1 knockdown were evaluated. Relative protein expression in the ataxia telangiectasia mutated kinase (ATM)-checkpoint kinase-2 (CHK2)-P53 pathway was measured by Western blot analysis to unravel the molecular mechanisms linking the pathway to the above phenomena. Icotinib hydrochloride increased the radiosensitivity of HCT116 cells; however, this effect was suppressed by the downregulation of 53BP1 expression, a change that inhibited cell apoptosis, increased the percentage of HCT116 cells arrested in S-phase and inhibited the protein expression of key molecules in the ATM-CHK2-P53 apoptotic pathway. Our studies confirmed that the loss of 53BP1 serves as a negative regulator of the radiosensitizing effect of icotinib in part by suppressing the ATM-CHK2-P53 apoptotic pathway.

Remedial investigation for the 200-BP-1 operable unit, Hanford Site, Richland, Washington

International Nuclear Information System (INIS)

Buckmaster, M.A.

1991-01-01

The Hanford Site, Richland, Washington, contains over 1500 identified waste sites that will be characterized and remediated over the next 30 years. In support of the ''Hanford Federal Facility Agreement and Consent Order,'' the US Department of Energy has initiated a remedial investigation/feasibility study (RI/FS) at the 200-BP-1 operable unit. The 200-BP-1 RI is the first Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) investigation on the Hanford Site that involves drilling into highly radioactive and chemically contaminated soils. The initial phase of the site characterization is oriented toward determining the nature and extent of any contamination present in the vicinity of the 200-BP-1 operable unit. The major focus of the Phase I RI is the drilling and sampling of 10 inactive waste disposal units which received low level radioactive liquid waste

AcEST: BP914061 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000039_D09 599 Adiantum capillus-veneris mRNA. clone: YMU001_000039_D09. BP91406...1 CL1730Contig1 Show BP914061 Clone id YMU001_000039_D09 Library YMU01 Length 599 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000039_D09. Accession BP914061 Tissue type prothallium Developmental stag... a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP914061|Adia...database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP914061|Adiantum capillus-veneris mRNA, c

AcEST: BP918013 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000108_F01 490 Adiantum capillus-veneris mRNA. clone: YMU001_000108_F01. BP918013 - Show BP91801...is mRNA. clone: YMU001_000108_F01. Accession BP918013 Tissue type prothallium Developmental stage - Contig I...protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP91801...idylinositol-4-phosphate 5-kinase 1 OS=Oryza sativa subsp. japonica GN=PIPK1 PE=2 SV=2 Length = 801 Score = ..., Gapped BLAST and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP91801

Association of 3BP2 with SHP-1 regulates SHP-1-mediated production of TNF-α in RBL-2H3 cells.

Science.gov (United States)

Chihara, Kazuyasu; Nakashima, Kenji; Takeuchi, Kenji; Sada, Kiyonao

2011-12-01

Adaptor protein 3BP2, a c-Abl Src homology 3 (SH3) domain-binding protein, is tyrosine phosphorylated and positively regulates mast cell signal transduction after the aggregation of the high affinity IgE receptor (FcεRI). Overexpression of the Src homology 2 (SH2) domain of 3BP2 results in the dramatic suppression of antigen-induced degranulation in rat basophilic leukemia RBL-2H3 cells. Previously, a linker for activation of T cells (LAT) was identified as one of the 3BP2 SH2 domain-binding protein. In this report, to further understand the functions of 3BP2 in FcεRI-mediated activation of mast cell, we explored the protein that associates with the SH2 domain of 3BP2 and found that SH2 domain-containing phosphatase-1 (SHP-1) inducibly interacts with the SH2 domain of 3BP2 after the aggregation of FcεRI. The phosphorylation of Tyr(564) in the carboxy (C)-terminal tail region of SHP-1 is required for the direct interaction of SHP-1 to the SH2 domain of 3BP2. The expression of the mutant form of SHP-1 which was unable to interact with 3BP2 resulted in the significant reduction in SHP-1-mediated tumor necrosis factor-α (TNF-α) production without any effects on the degranulation in antigen-stimulated RBL-2H3 cells. These findings suggest that 3BP2 directly interacts with Tyr(564) -phosphorylated form of SHP-1 and positively regulates the function of SHP-1 in FcεRI-mediated signaling in mast cells. © 2011 The Authors. Journal compilation © 2011 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.

The Arabidopsis homolog of human G3BP1 is a key regulator of stomatal and apoplastic immunity

KAUST Repository

Abulfaraj, Aala A.; Mariappan, Kiruthiga; Bigeard, Jean; Manickam, Prabhu; Blilou, Ikram; Guo, Xiujie; Al-Babili, Salim; Pflieger, Delphine; Hirt, Heribert; Rayapuram, Naganand

2018-01-01

Mammalian Ras-GTPase–activating protein SH3-domain–binding proteins (G3BPs) are a highly conserved family of RNA-binding proteins that link kinase receptor-mediated signaling to RNA metabolism. Mammalian G3BP1 is a multifunctional protein that functions in viral immunity. Here, we show that the Arabidopsis thaliana homolog of human G3BP1 negatively regulates plant immunity. Arabidopsis g3bp1 mutants showed enhanced resistance to the virulent bacterial pathogen Pseudomonas syringae pv. tomato. Pathogen resistance was mediated in Atg3bp1 mutants by altered stomatal and apoplastic immunity. Atg3bp1 mutants restricted pathogen entry into stomates showing insensitivity to bacterial coronatine–mediated stomatal reopening. AtG3BP1 was identified as a negative regulator of defense responses, which correlated with moderate up-regulation of salicylic acid biosynthesis and signaling without growth penalty.

The Arabidopsis homolog of human G3BP1 is a key regulator of stomatal and apoplastic immunity

KAUST Repository

Abulfaraj, Aala Abdulaziz Hussien

2018-05-31

Mammalian Ras-GTPase–activating protein SH3-domain–binding proteins (G3BPs) are a highly conserved family of RNA-binding proteins that link kinase receptor-mediated signaling to RNA metabolism. Mammalian G3BP1 is a multifunctional protein that functions in viral immunity. Here, we show that the Arabidopsis thaliana homolog of human G3BP1 negatively regulates plant immunity. Arabidopsis g3bp1 mutants showed enhanced resistance to the virulent bacterial pathogen Pseudomonas syringae pv. tomato. Pathogen resistance was mediated in Atg3bp1 mutants by altered stomatal and apoplastic immunity. Atg3bp1 mutants restricted pathogen entry into stomates showing insensitivity to bacterial coronatine–mediated stomatal reopening. AtG3BP1 was identified as a negative regulator of defense responses, which correlated with moderate up-regulation of salicylic acid biosynthesis and signaling without growth penalty.

Proportionate Dwarfism in Mice Lacking Heterochromatin Protein 1 Binding Protein 3 (HP1BP3) Is Associated With Alterations in the Endocrine IGF-1 Pathway.

Science.gov (United States)

Garfinkel, Benjamin P; Arad, Shiri; Le, Phuong T; Bustin, Michael; Rosen, Clifford J; Gabet, Yankel; Orly, Joseph

2015-12-01

Heterochromatin protein 1 binding protein 3 (HP1BP3) is a recently described histone H1-related protein with roles in chromatin structure and transcriptional regulation. To explore the potential physiological role of HP1BP3, we have previously described an Hp1bp3(-/-) mouse model with reduced postnatal viability and growth. We now find that these mice are proportionate dwarfs, with reduction in body weight, body length, and organ weight. In addition to their small size, microcomputed tomography analysis showed that Hp1bp3(-/-) mice present a dramatic impairment of their bone development and structure. By 3 weeks of age, mice of both sexes have severely impaired cortical and trabecular bone, and these defects persist into adulthood and beyond. Primary cultures of both osteoblasts and osteoclasts from Hp1bp3(-/-) bone marrow and splenocytes, respectively, showed normal differentiation and function, strongly suggesting that the impaired bone accrual is due to noncell autonomous systemic cues in vivo. One major endocrine pathway regulating both body growth and bone acquisition is the IGF regulatory system, composed of IGF-1, the IGF receptors, and the IGF-binding proteins (IGFBPs). At 3 weeks of age, Hp1bp3(-/-) mice exhibited a 60% reduction in circulating IGF-1 and a 4-fold increase in the levels of IGFBP-1 and IGFBP-2. These alterations were reflected in similar changes in the hepatic transcripts of the Igf1, Igfbp1, and Igfbp2 genes. Collectively, these results suggest that HP1BP3 plays a key role in normal growth and bone development by regulating transcription of endocrine IGF-1 components.

AcEST: BP920991 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000144_C04 521 Adiantum capillus-veneris mRNA. clone: YMU001_000144_C04. BP92099...1 CL3173Contig1 Show BP920991 Clone id YMU001_000144_C04 Library YMU01 Length 521 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000144_C04. Accession BP920991 Tissue type prothallium Developmental stag...s. 25:3389-3402. Query= BP920991|Adiantum capillus-veneris mRNA, clone: YMU001_000144_C04. (521 letters) Dat...ucleic Acids Res. 25:3389-3402. Query= BP920991|Adiantum capillus-veneris mRNA, clone: YMU001_000144_C04. (5

Proportionate Dwarfism in Mice Lacking Heterochromatin Protein 1 Binding Protein 3 (HP1BP3) Is Associated With Alterations in the Endocrine IGF-1 Pathway

OpenAIRE

Garfinkel, Benjamin P.; Arad, Shiri; Le, Phuong T.; Bustin, Michael; Rosen, Clifford J.; Gabet, Yankel; Orly, Joseph

2015-01-01

Heterochromatin protein 1 binding protein 3 (HP1BP3) is a recently described histone H1-related protein with roles in chromatin structure and transcriptional regulation. To explore the potential physiological role of HP1BP3, we have previously described an Hp1bp3?/? mouse model with reduced postnatal viability and growth. We now find that these mice are proportionate dwarfs, with reduction in body weight, body length, and organ weight. In addition to their small size, microcomputed tomography...

S6K1 and 4E-BP1 are independent regulated and control cellular growth in bladder cancer.

Directory of Open Access Journals (Sweden)

Roman Nawroth

Full Text Available Aberrant activation and mutation status of proteins in the phosphatidylinositol-3-kinase (PI3K/Akt/mammalian target of rapamycin (mTOR and the mitogen activated protein kinase (MAPK signaling pathways have been linked to tumorigenesis in various tumors including urothelial carcinoma (UC. However, anti-tumor therapy with small molecule inhibitors against mTOR turned out to be less successful than expected. We characterized the molecular mechanism of this pathway in urothelial carcinoma by interfering with different molecular components using small chemical inhibitors and siRNA technology and analyzed effects on the molecular activation status, cell growth, proliferation and apoptosis. In a majority of tested cell lines constitutive activation of the PI3K was observed. Manipulation of mTOR or Akt expression or activity only regulated phosphorylation of S6K1 but not 4E-BP1. Instead, we provide evidence for an alternative mTOR independent but PI3K dependent regulation of 4E-BP1. Only the simultaneous inhibition of both S6K1 and 4E-BP1 suppressed cell growth efficiently. Crosstalk between PI3K and the MAPK signaling pathway is mediated via PI3K and indirect by S6K1 activity. Inhibition of MEK1/2 results in activation of Akt but not mTOR/S6K1 or 4E-BP1. Our data suggest that 4E-BP1 is a potential new target molecule and stratification marker for anti cancer therapy in UC and support the consideration of a multi-targeting approach against PI3K, mTORC1/2 and MAPK.

GEMC1 is a TopBP1 interacting protein required for chromosomal DNA replication

Science.gov (United States)

Balestrini, Alessia; Cosentino, Claudia; Errico, Alessia; Garner, Elizabeth; Costanzo, Vincenzo

2010-01-01

Many factors required for chromosomal DNA replication have been identified in unicellular eukaryotes. However, DNA replication in complex multicellular organisms is poorly understood. Here, we report the identification of GEMC1, a novel vertebrate protein required for chromosomal DNA replication. GEMC1 is highly conserved in vertebrates and is preferentially expressed in proliferating cells. Using Xenopus egg extract we show that Xenopus GEMC1 (xGEMC1) binds to checkpoint and replication factor TopBP1, which promotes xGEMC1 binding to chromatin during pre-replication complex (pre-RC) formation. We demonstrate that xGEMC1 directly interacts with replication factors such as Cdc45 and Cdk2-CyclinE by which it is heavily phosphorylated. Phosphorylated xGEMC1 stimulates initiation of DNA replication whereas depletion of xGEMC1 prevents DNA replication onset due to impairment of Cdc45 loading onto chromatin. Likewise, inhibition of GEMC1 expression by morpholino and siRNA oligos prevents DNA replication in embryonic and somatic vertebrate cells. These data suggest that GEMC1 promotes initiation of chromosomal DNA replication in higher eukaryotes by mediating TopBP1 and Cdk2 dependent recruitment of Cdc45 onto replication origins. PMID:20383140

AcEST: BP918012 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000108_E12 547 Adiantum capillus-veneris mRNA. clone: YMU001_000108_E12. BP918012 - Show BP91801...is mRNA. clone: YMU001_000108_E12. Accession BP918012 Tissue type prothallium Developmental stage - Contig I...grams, Nucleic Acids Res. 25:3389-3402. Query= BP918012|Adiantum capillus-veneris mRNA, clone: YMU001_000108...ms, Nucleic Acids Res. 25:3389-3402. Query= BP918012|Adiantum capillus-veneris mRNA, clone: YMU001_000108_E1

Increased 4E-BP1 Expression Protects against Diet-Induced Obesity and Insulin Resistance in Male Mice

Directory of Open Access Journals (Sweden)

Shih-Yin Tsai

2016-08-01

Full Text Available Obesity is a major risk factor driving the global type II diabetes pandemic. However, the molecular factors linking obesity to disease remain to be elucidated. Gender differences are apparent in humans and are also observed in murine models. Here, we link these differences to expression of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1, which, upon HFD feeding, becomes significantly reduced in the skeletal muscle and adipose tissue of male but not female mice. Strikingly, restoring 4E-BP1 expression in male mice protects them against HFD-induced obesity and insulin resistance. Male 4E-BP1 transgenic mice also exhibit reduced white adipose tissue accumulation accompanied by decreased circulating levels of leptin and triglycerides. Importantly, transgenic 4E-BP1 male mice are also protected from aging-induced obesity and metabolic decline on a normal diet. These results demonstrate that 4E-BP1 is a gender-specific suppressor of obesity that regulates insulin sensitivity and energy metabolism.

AcEST: BP912406 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000018_F09 348 Adiantum capillus-veneris mRNA. clone: YMU001_000018_F09. BP912406... CL1894Contig1 Show BP912406 Clone id YMU001_000018_F09 Library YMU01 Length 348 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000018_F09. Accession BP912406 Tissue type prothallium Developmental stag...in database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP912406|Adiantum capillus-veneris mRNA...n of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP912406

AcEST: BP917406 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000100_D10 492 Adiantum capillus-veneris mRNA. clone: YMU001_000100_D10. BP917406... CL2033Contig1 Show BP917406 Clone id YMU001_000100_D10 Library YMU01 Length 492 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000100_D10. Accession BP917406 Tissue type prothallium Developmental stag...of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP917406...Nucleic Acids Res. 25:3389-3402. Query= BP917406|Adiantum capillus-veneris mRNA,

AcEST: BP916801 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000091_G06 127 Adiantum capillus-veneris mRNA. clone: YMU001_000091_G06. BP916801... CL2168Contig1 Show BP916801 Clone id YMU001_000091_G06 Library YMU01 Length 127 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000091_G06. Accession BP916801 Tissue type prothallium Developmental stag...ds Res. 25:3389-3402. Query= BP916801|Adiantum capillus-veneris mRNA, clone: YMU0...a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP916801

AcEST: BP913801 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000035_D11 562 Adiantum capillus-veneris mRNA. clone: YMU001_000035_D11. BP913801... CL482Contig1 Show BP913801 Clone id YMU001_000035_D11 Library YMU01 Length 562 Definition Adiantum cap...illus-veneris mRNA. clone: YMU001_000035_D11. Accession BP913801 Tissue type prothallium Developmental stage...tabase search programs, Nucleic Acids Res. 25:3389-3402. Query= BP913801|Adiantum...earch programs, Nucleic Acids Res. 25:3389-3402. Query= BP913801|Adiantum capillus-veneris mRNA, clone: YMU0

AcEST: BP920801 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000141_G10 454 Adiantum capillus-veneris mRNA. clone: YMU001_000141_G10. BP920801... CL819Contig1 Show BP920801 Clone id YMU001_000141_G10 Library YMU01 Length 454 Definition Adiantum cap...illus-veneris mRNA. clone: YMU001_000141_G10. Accession BP920801 Tissue type prothallium Developmental stage... Acids Res. 25:3389-3402. Query= BP920801|Adiantum capillus-veneris mRNA, clone: ...ion of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP920801|Adiantum capillus-

AcEST: BP912122 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000015_D04 544 Adiantum capillus-veneris mRNA. clone: YMU001_000015_D04. BP91212...2 CL3363Contig1 Show BP912122 Clone id YMU001_000015_D04 Library YMU01 Length 544 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000015_D04. Accession BP912122 Tissue type prothallium Developmental stag...obium aromaticivorans (strain DSM 12444) Align length 58 Score (bit) 33.1 E-value 0.89 Report BLASTX 2.2.19 ...w generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP912122|Adiantum

GEMC1 is a TopBP1-interacting protein required for chromosomal DNA replication.

Science.gov (United States)

Balestrini, Alessia; Cosentino, Claudia; Errico, Alessia; Garner, Elizabeth; Costanzo, Vincenzo

2010-05-01

Many of the factors required for chromosomal DNA replication have been identified in unicellular eukaryotes. However, DNA replication is poorly understood in multicellular organisms. Here, we report the identification of GEMC1 (geminin coiled-coil containing protein 1), a novel vertebrate protein required for chromosomal DNA replication. GEMC1 is highly conserved in vertebrates and is preferentially expressed in proliferating cells. Using Xenopus laevis egg extract we show that Xenopus GEMC1 (xGEMC1) binds to the checkpoint and replication factor TopBP1, which promotes binding of xGEMC1 to chromatin during pre-replication complex (pre-RC) formation. We demonstrate that xGEMC1 interacts directly with replication factors such as Cdc45 and the kinase Cdk2-CyclinE, through which it is heavily phosphorylated. Phosphorylated xGEMC1 stimulates initiation of DNA replication, whereas depletion of xGEMC1 prevents the onset of DNA replication owing to the impairment of Cdc45 loading onto chromatin. Similarly, inhibition of GEMC1 expression with morpholino and siRNA oligos prevents DNA replication in embryonic and somatic vertebrate cells. These data suggest that GEMC1 promotes initiation of chromosomal DNA replication in multicellular organisms by mediating TopBP1- and Cdk2-dependent recruitment of Cdc45 onto replication origins.

AcEST: BP920140 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000133_E03 489 Adiantum capillus-veneris mRNA. clone: YMU001_000133_E03. BP92014...0 CL2574Contig1 Show BP920140 Clone id YMU001_000133_E03 Library YMU01 Length 489 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000133_E03. Accession BP920140 Tissue type prothallium Developmental stag... database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP920140|Adian... and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP92014

AcEST: BP920143 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000133_E07 533 Adiantum capillus-veneris mRNA. clone: YMU001_000133_E07. BP92014...3 CL2377Contig1 Show BP920143 Clone id YMU001_000133_E07 Library YMU01 Length 533 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000133_E07. Accession BP920143 Tissue type prothallium Developmental stag...ms, Nucleic Acids Res. 25:3389-3402. Query= BP920143|Adiantum capillus-veneris mRNA, clone: YMU001_000133_E0...tabase search programs, Nucleic Acids Res. 25:3389-3402. Query= BP920143|Adiantum

AcEST: BP920146 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000133_E12 401 Adiantum capillus-veneris mRNA. clone: YMU001_000133_E12. BP92014...6 CL388Contig1 Show BP920146 Clone id YMU001_000133_E12 Library YMU01 Length 401 Definition Adiantum cap...illus-veneris mRNA. clone: YMU001_000133_E12. Accession BP920146 Tissue type prothallium Developmental stage...generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP920146|Adiantum ca...rams, Nucleic Acids Res. 25:3389-3402. Query= BP920146|Adiantum capillus-veneris mRNA, clone: YMU001_000133_

AcEST: BP920148 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000133_F02 429 Adiantum capillus-veneris mRNA. clone: YMU001_000133_F02. BP92014...8 CL3819Contig1 Show BP920148 Clone id YMU001_000133_F02 Library YMU01 Length 429 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000133_F02. Accession BP920148 Tissue type prothallium Developmental stag...rograms, Nucleic Acids Res. 25:3389-3402. Query= BP920148|Adiantum capillus-vener...ed BLAST and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP92014

AcEST: BP920149 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000133_F03 624 Adiantum capillus-veneris mRNA. clone: YMU001_000133_F03. BP92014...9 CL2860Contig1 Show BP920149 Clone id YMU001_000133_F03 Library YMU01 Length 624 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000133_F03. Accession BP920149 Tissue type prothallium Developmental stag...ic Acids Res. 25:3389-3402. Query= BP920149|Adiantum capillus-veneris mRNA, clone: YMU001_000133_F03. (624 l...n of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP92014

AcEST: BP914065 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000039_E01 548 Adiantum capillus-veneris mRNA. clone: YMU001_000039_E01. BP91406...5 CL604Contig1 Show BP914065 Clone id YMU001_000039_E01 Library YMU01 Length 548 Definition Adiantum cap...illus-veneris mRNA. clone: YMU001_000039_E01. Accession BP914065 Tissue type prothallium Developmental stage...earch programs, Nucleic Acids Res. 25:3389-3402. Query= BP914065|Adiantum capillus-veneris mRNA, clone: YMU0...cids Res. 25:3389-3402. Query= BP914065|Adiantum capillus-veneris mRNA, clone: YMU001_000039_E01. (548 lette

AcEST: BP914069 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000039_E05 368 Adiantum capillus-veneris mRNA. clone: YMU001_000039_E05. BP91406...9 CL2761Contig1 Show BP914069 Clone id YMU001_000039_E05 Library YMU01 Length 368 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000039_E05. Accession BP914069 Tissue type prothallium Developmental stag...rograms, Nucleic Acids Res. 25:3389-3402. Query= BP914069|Adiantum capillus-veneris mRNA, clone: YMU001_0000...rch programs, Nucleic Acids Res. 25:3389-3402. Query= BP914069|Adiantum capillus-veneris mRNA, clone: YMU001

AcEST: BP914064 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000039_D12 560 Adiantum capillus-veneris mRNA. clone: YMU001_000039_D12. BP91406...4 CL532Contig1 Show BP914064 Clone id YMU001_000039_D12 Library YMU01 Length 560 Definition Adiantum cap...illus-veneris mRNA. clone: YMU001_000039_D12. Accession BP914064 Tissue type prothallium Developmental stage...f protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP914064|Adiantum capillus-vener...: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP914064|Adi

AcEST: BP916406 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000087_D01 556 Adiantum capillus-veneris mRNA. clone: YMU001_000087_D01. BP916406... CL1913Contig1 Show BP916406 Clone id YMU001_000087_D01 Library YMU01 Length 556 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000087_D01. Accession BP916406 Tissue type prothallium Developmental stag...ration of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP916406|Adiantum capill...database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP916406|Adiantum capillus-veneris mRNA, c

AcEST: BP914406 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000058_E09 562 Adiantum capillus-veneris mRNA. clone: YMU001_000058_E09. BP914406... CL513Contig1 Show BP914406 Clone id YMU001_000058_E09 Library YMU01 Length 562 Definition Adiantum cap...illus-veneris mRNA. clone: YMU001_000058_E09. Accession BP914406 Tissue type prothallium Developmental stage...tion of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP914406|Adiantum capillus...PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP914406

AcEST: BP914060 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000039_D08 539 Adiantum capillus-veneris mRNA. clone: YMU001_000039_D08. BP91406...0 CL1835Contig1 Show BP914060 Clone id YMU001_000039_D08 Library YMU01 Length 539 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000039_D08. Accession BP914060 Tissue type prothallium Developmental stag...rotein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP914060|Adiantum capillus-veneris ...Acids Res. 25:3389-3402. Query= BP914060|Adiantum capillus-veneris mRNA, clone: YMU001_000039_D08. (539 lett

AcEST: BP920998 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000144_D03 529 Adiantum capillus-veneris mRNA. clone: YMU001_000144_D03. BP92099...8 CL1935Contig1 Show BP920998 Clone id YMU001_000144_D03 Library YMU01 Length 529 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000144_D03. Accession BP920998 Tissue type prothallium Developmental stag...abase search programs, Nucleic Acids Res. 25:3389-3402. Query= BP920998|Adiantum capillus-veneris mRNA, clon... of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP920998|Adiantum capillus-ven

AcEST: BP920999 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000144_D04 588 Adiantum capillus-veneris mRNA. clone: YMU001_000144_D04. BP92099...9 CL317Contig1 Show BP920999 Clone id YMU001_000144_D04 Library YMU01 Length 588 Definition Adiantum cap...illus-veneris mRNA. clone: YMU001_000144_D04. Accession BP920999 Tissue type prothallium Developmental stage...nd PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP92099... and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP92099

AcEST: BP920996 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000144_D01 496 Adiantum capillus-veneris mRNA. clone: YMU001_000144_D01. BP92099...6 CL262Contig1 Show BP920996 Clone id YMU001_000144_D01 Library YMU01 Length 496 Definition Adiantum cap...illus-veneris mRNA. clone: YMU001_000144_D01. Accession BP920996 Tissue type prothallium Developmental stage...n of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP92099...n of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP920996|Adiantum capillus-ve

AcEST: BP920993 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000144_C06 517 Adiantum capillus-veneris mRNA. clone: YMU001_000144_C06. BP92099...3 CL547Contig1 Show BP920993 Clone id YMU001_000144_C06 Library YMU01 Length 517 Definition Adiantum cap...illus-veneris mRNA. clone: YMU001_000144_C06. Accession BP920993 Tissue type prothallium Developmental stage...rograms, Nucleic Acids Res. 25:3389-3402. Query= BP920993|Adiantum capillus-veneris mRNA, clone: YMU001_0001...w generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP920993|Adiantum

AcEST: BP920992 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000144_C05 525 Adiantum capillus-veneris mRNA. clone: YMU001_000144_C05. BP92099...2 CL2523Contig1 Show BP920992 Clone id YMU001_000144_C05 Library YMU01 Length 525 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000144_C05. Accession BP920992 Tissue type prothallium Developmental stag...Acids Res. 25:3389-3402. Query= BP920992|Adiantum capillus-veneris mRNA, clone: YMU001_000144_C05. (525 lett...ograms, Nucleic Acids Res. 25:3389-3402. Query= BP920992|Adiantum capillus-veneris mRNA, clone: YMU001_00014

AcEST: BP919801 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000129_C11 513 Adiantum capillus-veneris mRNA. clone: YMU001_000129_C11. BP919801... CL1Contig3 Show BP919801 Clone id YMU001_000129_C11 Library YMU01 Length 513 Definition Adiantum capil...lus-veneris mRNA. clone: YMU001_000129_C11. Accession BP919801 Tissue type prothallium Developmental stage -...es. 25:3389-3402. Query= BP919801|Adiantum capillus-veneris mRNA, clone: YMU001_000129_C11. (435 letters) Da...eration of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP919801|Adiantum capil

AcEST: BP914801 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000063_A07 396 Adiantum capillus-veneris mRNA. clone: YMU001_000063_A07. BP914801... CL1121Contig1 Show BP914801 Clone id YMU001_000063_A07 Library YMU01 Length 396 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000063_A07. Accession BP914801 Tissue type prothallium Developmental stag...ped BLAST and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP914801...ase search programs, Nucleic Acids Res. 25:3389-3402. Query= BP914801|Adiantum capillus-veneris mRNA, clone:

Association between interleukin 1 receptor antagonist gene 86-bp VNTR polymorphism and sepsis: a meta-analysis.

Science.gov (United States)

Fang, Fang; Pan, Jian; Li, Yiping; Xu, Lixiao; Su, Guanghao; Li, Gang; Wang, Jian

2015-01-01

Many studies have focused on the relationship between interleukin 1 receptor antagonist (IL1RN) gene 86-bp VNTR polymorphism and sepsis, but the results remain inconsistent. Thus, a meta-analysis was carried out to derive a more precise estimation of the association between IL1RN 86-bp VNTR polymorphism and risk of sepsis and sepsis-related mortality. Relevant publications were searched in several widely used databases and six eligible studies were included in the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between IL1RN 86-bp VNTR polymorphism and risk of sepsis and sepsis-related mortality. Significant associations between IL1RN 86-bp VNTR polymorphism and sepsis risk were observed in both overall meta-analysis for L2 versus 22 (OR=0.75, 95% CI=0.59-0.94) and severe sepsis subgroup for LL+L2 versus 22 (OR=0.67, 95% CI=0.47-0.93). L stands for long alleles containing three to six repeats; 2 stands for short allele containing two repeats. However, no significant sepsis mortality variation was detected for all genetic models. According to the results of our meta-analysis, the IL1RN 86-bp VNTR polymorphism probably associates with sepsis risk but not with sepsis-related mortality. Copyright © 2014. Published by Elsevier Inc.

Feasibility study report for the 200-BP-1 operable unit

Energy Technology Data Exchange (ETDEWEB)

1993-06-01

This feasibility study examines a range of alternatives and provides recommendations for selecting a preferred alternative for remediating contamination at the 200-BP-1 operable unit. The 200-BP-1 operable unit is located in the center of the Hanford Site along the northern boundary of the 200 East Area. The 241-BY Tank Farm is located immediately to the south of the operable unit. 200-BP-1 is a source operable unit with contaminated soils associated primarily with nine inactive cribs (known as the 216-B cribs). These cribs were used for disposal of low-level radioactive liquid waste from U Plant uranium recovery operations, and waste storage tank condensate from the adjacent 241-BY Tank Farm. The cribs used for disposal of U Plant waste were in operation from 1955--1965, and the cribs used for disposal of tank condensate were in operation from 1965--1975. In addition to the cribs, four unplanned releases of radioactive materials have occurred within the operable unit. Contaminated surface soils associated with the unplanned releases have been consolidated over the cribs and covered with clean soil to reduce contaminant migration and exposure. Discharge of wastes to the cribs has resulted in soil and groundwater contamination. The groundwater is being addressed as part of the 200 East Aggregate Area, groundwater operable unit. Contaminated soils at the site can be categorized by the types of contaminants, their distribution in the soil column, and the risk posed by the various potential exposure pathways. Below the clean soil cover, the near surface soils contain low-levels of contamination with cesium-137, radium-226, strontium-90, thorium-228, and uranium. The lifetime incremental cancer risk associated with these soils if they were exposed at the surface is 9{times}10{sup {minus}5}.

Feasibility study report for the 200-BP-1 operable unit

International Nuclear Information System (INIS)

1993-06-01

This feasibility study examines a range of alternatives and provides recommendations for selecting a preferred alternative for remediating contamination at the 200-BP-1 operable unit. The 200-BP-1 operable unit is located in the center of the Hanford Site along the northern boundary of the 200 East Area. The 241-BY Tank Farm is located immediately to the south of the operable unit. 200-BP-1 is a source operable unit with contaminated soils associated primarily with nine inactive cribs (known as the 216-B cribs). These cribs were used for disposal of low-level radioactive liquid waste from U Plant uranium recovery operations, and waste storage tank condensate from the adjacent 241-BY Tank Farm. The cribs used for disposal of U Plant waste were in operation from 1955--1965, and the cribs used for disposal of tank condensate were in operation from 1965--1975. In addition to the cribs, four unplanned releases of radioactive materials have occurred within the operable unit. Contaminated surface soils associated with the unplanned releases have been consolidated over the cribs and covered with clean soil to reduce contaminant migration and exposure. Discharge of wastes to the cribs has resulted in soil and groundwater contamination. The groundwater is being addressed as part of the 200 East Aggregate Area, groundwater operable unit. Contaminated soils at the site can be categorized by the types of contaminants, their distribution in the soil column, and the risk posed by the various potential exposure pathways. Below the clean soil cover, the near surface soils contain low-levels of contamination with cesium-137, radium-226, strontium-90, thorium-228, and uranium. The lifetime incremental cancer risk associated with these soils if they were exposed at the surface is 9x10 -5

Feasibility study report for the 200-BP-1 operable unit

International Nuclear Information System (INIS)

1994-01-01

This feasibility study (FS) examines a range of alternatives and provides recommendations for selecting a preferred altemative for remediating contamination at the 200-BP-1 operable unit. The 200-BP-1 operable unit is located in the center of the Hanford Site along the northern boundary of the 200 East Area. The 241-BY Tank Farm is located immediately to the south of the operable unit. 200-BP-1 is a source operable unit with contaminated soils associated primarily with nine inactive cribs (known as the 216-B cribs). These cribs were used for disposal of low-level radioactive liquid waste from U Plant uranium recovery operations, and waste storage tank condensate from the adjacent 241-BY Tank Farm. The cribs used for disposal of U Plant waste were in operation from 1955--1965, and the cribs used for disposal of tank condensate were in operation from 1965-1975. In addition to the cribs, four unplanned releases of radioactive materials have occurred within the operable unit. Contaminated surface soils associated with the unplanned releases have been consolidated over the cribs and covered with clean soil to reduce contaminant migration and exposure. Discharge of wastes to the cribs has resulted in soil and groundwater contamination. The groundwater is being addressed as part of the 200 East Aggregate Area groundwater operable unit. Contaminated soils at the site can be categorized by the types of contaminants, their distribution in the soil column, and the risk posed by the various potential exposure pathways. Below the clean soil cover, the near surface soils contain low-:levels of contamination with cesium-137, radium-226, strontium-90, thorium-228 and uranium. The lifetime incremental cancer risk associated with these soils if they were exposed at the surface is 9 x 10 5

AcEST: BP920994 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000144_C10 322 Adiantum capillus-veneris mRNA. clone: YMU001_000144_C10. BP92099...4 CL2871Contig1 Show BP920994 Clone id YMU001_000144_C10 Library YMU01 Length 322 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000144_C10. Accession BP920994 Tissue type prothallium Developmental stag...), Gapped BLAST and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP92099...ped BLAST and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP92099

AcEST: BP920990 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000144_C03 445 Adiantum capillus-veneris mRNA. clone: YMU001_000144_C03. BP92099...0 CL4123Contig1 Show BP920990 Clone id YMU001_000144_C03 Library YMU01 Length 445 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000144_C03. Accession BP920990 Tissue type prothallium Developmental stag...97), Gapped BLAST and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP9209...LAST and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP92099

AcEST: BP918016 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000108_F04 434 Adiantum capillus-veneris mRNA. clone: YMU001_000108_F04. BP91801...6 CL3779Contig1 Show BP918016 Clone id YMU001_000108_F04 Library YMU01 Length 434 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000108_F04. Accession BP918016 Tissue type prothallium Developmental stag..., Gapped BLAST and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP91801...ic Acids Res. 25:3389-3402. Query= BP918016|Adiantum capillus-veneris mRNA, clone: YMU001_000108_F04. (434 l

Acute Toxicity and Ecological Risk Assessment of Benzophenone-3 (BP-3 and Benzophenone-4 (BP-4 in Ultraviolet (UV-Filters

Directory of Open Access Journals (Sweden)

Yang Du

2017-11-01

Full Text Available Ultraviolet (UV-absorbing chemicals (UV filters are used in personal care products for the protection of human skin and hair from damage by UV radiation. Although these substances are released into the environment in the production and consumption processes, little is known about their ecotoxicology effects. The acute toxicity and potential ecological risk of UV filters benzophenone-3 (BP-3 and benzophenone-4 (BP-4 on Chlorella vulgaris, Daphnia magna, and Brachydanio rerio were analyzed in the present study. The EC50 values (96 h of BP-3 and BP-4 on C. vulgaris were 2.98 and 201.00 mg/L, respectively. The 48 h-LC50 of BP-3 and BP-4 on D. magna were 1.09 and 47.47 mg/L, respectively. The 96 h-LC50 of BP-3 and BP-4 on B. rerio were 3.89 and 633.00 mg/L, respectively. The toxicity of a mixture of BP-3 and BP-4 on C. vulgaris, D. magna, and B. rerio all showed antagonistic effects. The induced predicted no-effect concentrations of BP-3 and BP-4 by the assessment factor method were 1.80 × 10−3 and 0.47 mg/L, respectively, by assessment factor (AF method, which were both lower than the concentrations detected in the environment at present, verifying that BP-3 and BP-4 remain low-risk chemicals to the aquatic ecosystem.

53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress

DEFF Research Database (Denmark)

Lukas, Claudia; Savic, Velibor; Bekker-Jensen, Simon

2011-01-01

stress increases the frequency of chromosomal lesions that are transmitted to daughter cells. Throughout G1, these lesions are sequestered in nuclear compartments marked by p53-binding protein 1 (53BP1) and other chromatin-associated genome caretakers. We show that the number of such 53BP1 nuclear bodies...... increases after genetic ablation of BLM, a DNA helicase associated with dissolution of entangled DNA. Conversely, 53BP1 nuclear bodies are partially suppressed by knocking down SMC2, a condensin subunit required for mechanical stability of mitotic chromosomes. Finally, we provide evidence that 53BP1 nuclear...... bodies shield chromosomal fragile sites sequestered in these compartments against erosion. Together, these data indicate that restoration of DNA or chromatin integrity at loci prone to replication problems requires mitotic transmission to the next cell generations....

AcEST: BP912212 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000016_D11 457 Adiantum capillus-veneris mRNA. clone: YMU001_000016_D11. BP912212... CL1085Contig1 Show BP912212 Clone id YMU001_000016_D11 Library YMU01 Length 457 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000016_D11. Accession BP912212 Tissue type prothallium Developmental stag...f protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP912212...|Adiantum capillus-veneris mRNA, clone: YMU001_000016_D11. (457 letters) Database: uniprot_sprot.fasta 412

AcEST: BP912312 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000017_F01 489 Adiantum capillus-veneris mRNA. clone: YMU001_000017_F01. BP912312... CL1779Contig1 Show BP912312 Clone id YMU001_000017_F01 Library YMU01 Length 489 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000017_F01. Accession BP912312 Tissue type prothallium Developmental stag...on of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP912312...|Adiantum capillus-veneris mRNA, clone: YMU001_000017_F01. (489 letters) Database: uniprot_sprot.fasta 412

AcEST: BP912128 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000015_D10 477 Adiantum capillus-veneris mRNA. clone: YMU001_000015_D10. BP91212...8 CL2328Contig1 Show BP912128 Clone id YMU001_000015_D10 Library YMU01 Length 477 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000015_D10. Accession BP912128 Tissue type prothallium Developmental stag... protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP91212...8|Adiantum capillus-veneris mRNA, clone: YMU001_000015_D10. (461 letters) Database: uniprot_sprot.fasta 412

AcEST: BP912912 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000024_C05 413 Adiantum capillus-veneris mRNA. clone: YMU001_000024_C05. BP912912... CL1433Contig1 Show BP912912 Clone id YMU001_000024_C05 Library YMU01 Length 413 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000024_C05. Accession BP912912 Tissue type prothallium Developmental stag... of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP912912|Adiantum capillus-ven...eris mRNA, clone: YMU001_000024_C05. (413 letters) Database: uniprot_sprot.fasta 412

AcEST: BP919999 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000131_G09 554 Adiantum capillus-veneris mRNA. clone: YMU001_000131_G09. BP919999... CL2968Contig1 Show BP919999 Clone id YMU001_000131_G09 Library YMU01 Length 554 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000131_G09. Accession BP919999 Tissue type prothallium Developmental stag...b Miller, and David J. Lipman (1997), Gapped BLAST and PSI-BLAST: a new generatio...n of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP919999|Adiantum capillus-ve

AcEST: BP920997 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000144_D02 534 Adiantum capillus-veneris mRNA. clone: YMU001_000144_D02. BP92099...7 CL10Contig1 Show BP920997 Clone id YMU001_000144_D02 Library YMU01 Length 534 Definition Adiantum capi...llus-veneris mRNA. clone: YMU001_000144_D02. Accession BP920997 Tissue type prothallium Developmental stage ...a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP920997|Adian...BLAST: a new generation of protein database search programs, Nucleic Acids Res. 2

Interaction of CtBP with adenovirus E1A suppresses immortalization of primary epithelial cells and enhances virus replication during productive infection.

Science.gov (United States)

Subramanian, T; Zhao, Ling-Jun; Chinnadurai, G

2013-09-01

Adenovirus E1A induces cell proliferation, oncogenic transformation and promotes viral replication through interaction with p300/CBP, TRRAP/p400 multi-protein complex and the retinoblastoma (pRb) family proteins through distinct domains in the E1A N-terminal region. The C-terminal region of E1A suppresses E1A/Ras co-transformation and interacts with FOXK1/K2, DYRK1A/1B/HAN11 and CtBP1/2 (CtBP) protein complexes. To specifically dissect the role of CtBP interaction with E1A, we engineered a mutation (DL→AS) within the CtBP-binding motif, PLDLS, and investigated the effect of the mutation on immortalization and Ras cooperative transformation of primary cells and viral replication. Our results suggest that CtBP-E1A interaction suppresses immortalization and Ras co-operative transformation of primary rodent epithelial cells without significantly influencing the tumorigenic activities of transformed cells in immunodeficient and immunocompetent animals. During productive infection, CtBP-E1A interaction enhances viral replication in human cells. Between the two CtBP family proteins, CtBP2 appears to restrict viral replication more than CtBP1 in human cells. Copyright © 2013 Elsevier Inc. All rights reserved.

Identification and characterization of a carboxysomal γ-carbonic anhydrase from the cyanobacterium Nostoc sp. PCC 7120.

Science.gov (United States)

de Araujo, Charlotte; Arefeen, Dewan; Tadesse, Yohannes; Long, Benedict M; Price, G Dean; Rowlett, Roger S; Kimber, Matthew S; Espie, George S

2014-09-01

Carboxysomes are proteinaceous microcompartments that encapsulate carbonic anhydrase (CA) and ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco); carboxysomes, therefore, catalyze reversible HCO3 (-) dehydration and the subsequent fixation of CO2. The N- and C-terminal domains of the β-carboxysome scaffold protein CcmM participate in a network of protein-protein interactions that are essential for carboxysome biogenesis, organization, and function. The N-terminal domain of CcmM in the thermophile Thermosynechococcus elongatus BP-1 is also a catalytically active, redox regulated γ-CA. To experimentally determine if CcmM from a mesophilic cyanobacterium is active, we cloned, expressed and purified recombinant, full-length CcmM from Nostoc sp. PCC 7120 as well as the N-terminal 209 amino acid γ-CA-like domain. Both recombinant proteins displayed ethoxyzolamide-sensitive CA activity in mass spectrometric assays, as did the carboxysome-enriched TP fraction. NstCcmM209 was characterized as a moderately active and efficient γ-CA with a k cat of 2.0 × 10(4) s(-1) and k cat/K m of 4.1 × 10(6) M(-1) s(-1) at 25 °C and pH 8, a pH optimum between 8 and 9.5 and a temperature optimum spanning 25-35 °C. NstCcmM209 also catalyzed the hydrolysis of the CO2 analog carbonyl sulfide. Circular dichroism and intrinsic tryptophan fluorescence analysis demonstrated that NstCcmM209 was progressively and irreversibly denatured above 50 °C. NstCcmM209 activity was inhibited by the reducing agent tris(hydroxymethyl)phosphine, an effect that was fully reversed by a molar excess of diamide, a thiol oxidizing agent, consistent with oxidative activation being a universal regulatory mechanism of CcmM orthologs. Immunogold electron microscopy and Western blot analysis of TP pellets indicated that Rubisco and CcmM co-localize and are concentrated in Nostoc sp. PCC 7120 carboxysomes.

Pod-1/Capsulin shows a sex- and stage-dependent expression pattern in the mouse gonad development and represses expression of Ad4BP/SF-1.

Science.gov (United States)

Tamura, M; Kanno, Y; Chuma, S; Saito, T; Nakatsuji, N

2001-04-01

Mammalian sex-determination and differentiation are controlled by several genes, such as Sry, Sox-9, Dax-1 and Mullerian inhibiting substance (MIS), but their upstream and downstream genes are largely unknown. Ad4BP/SF-1, encoding a zinc finger transcription factor, plays important roles in gonadogenesis. Disruption of this gene caused disappearance of the urogenital system including the gonad. Ad4BP/SF-1, however, is also involved in the sex differentiation of the gonad at later stages, such as the regulation of steroid hormones and MIS. Pod-1/Capsulin, a member of basic helix-loop-helix transcription factors, is expressed in a pattern closely related but mostly complimentary to that of the Ad4BP/SF-1 expression in the developing gonad. In the co-transfection experiment using cultured cells, overexpression of Pod-1/Capsulin repressed expression of a reporter gene that carried the upstream regulatory region of the Ad4BP/SF-1 gene. Furthermore, forced expression of Pod-1/Capsulin repressed expression of Ad4BP/SF-1 in the Leydig cell-derived I-10 cells. These results suggest that Pod-1/Capsulin may play important roles in the development and sex differentiation of the mammalian gonad via transcriptional regulation of Ad4BP/SF-1.

AcEST: BP913636 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000032_E04 520 Adiantum capillus-veneris mRNA. clone: YMU001_000032_E04. BP913636... CL2643Contig1 Show BP913636 Clone id YMU001_000032_E04 Library YMU01 Length 520 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000032_E04. Accession BP913636 Tissue type prothallium Developmental stag...ograms, Nucleic Acids Res. 25:3389-3402. Query= BP913636|Adiantum capillus-veneris mRNA, clone: YMU001_00003...tative phospholipid-transporting ATPase ... 149 8e-36 sp|Q9LNQ4|ALA4_ARATH Putati

AcEST: BP912124 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000015_D06 531 Adiantum capillus-veneris mRNA. clone: YMU001_000015_D06. BP91212...4 CL2988Contig1 Show BP912124 Clone id YMU001_000015_D06 Library YMU01 Length 531 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000015_D06. Accession BP912124 Tissue type prothallium Developmental stag...n database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP912124|Adiantum capillus-veneris mRNA,... clone: YMU001_000015_D06. (531 letters) Database: uniprot_sprot.fasta 412,525 sequences; 148,809,765 total

AcEST: BP912125 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000015_D07 558 Adiantum capillus-veneris mRNA. clone: YMU001_000015_D07. BP912125 - Show BP91212...is mRNA. clone: YMU001_000015_D07. Accession BP912125 Tissue type prothallium Developmental stage - Contig I...ein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP912125|Adiantum capillus-veneris mRN...A, clone: YMU001_000015_D07. (558 letters) Database: uniprot_sprot.fasta 412,525 sequences; 148,809,765 tota...copeptide repeat-containing protein At1g08070 OS=Arabidopsis thaliana GN=PCMP-H12

AcEST: BP912120 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000015_D01 500 Adiantum capillus-veneris mRNA. clone: YMU001_000015_D01. BP912120 - Show BP91212...is mRNA. clone: YMU001_000015_D01. Accession BP912120 Tissue type prothallium Developmental stage - Contig I...elated Pol polyprotein from transposon TNT 1-94 OS=Nicotiana tabacum Align length 130 Score (bit) 124.0 E-va...: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP91212...0|Adiantum capillus-veneris mRNA, clone: YMU001_000015_D01. (500 letters) Database: uniprot_sprot.fasta 412

AcEST: BP912126 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000015_D08 484 Adiantum capillus-veneris mRNA. clone: YMU001_000015_D08. BP912126 CL412...4Contig1 Show BP912126 Clone id YMU001_000015_D08 Library YMU01 Length 484 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000015_D08. Accession BP912126 Tissue type prothallium Developmental stage - Contig ID CL412...-BLAST: a new generation of protein database search programs, Nucleic Acids Res. ...25:3389-3402. Query= BP912126|Adiantum capillus-veneris mRNA, clone: YMU001_000015_D08. (484 letters) Databa

AcEST: BP912812 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000023_B07 575 Adiantum capillus-veneris mRNA. clone: YMU001_000023_B07. BP912812... CL2610Contig1 Show BP912812 Clone id YMU001_000023_B07 Library YMU01 Length 575 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000023_B07. Accession BP912812 Tissue type prothallium Developmental stag... new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP912812|Adiant...um capillus-veneris mRNA, clone: YMU001_000023_B07. (575 letters) Database: uniprot_sprot.fasta 412,525 sequ

AcEST: BP912412 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000018_G03 551 Adiantum capillus-veneris mRNA. clone: YMU001_000018_G03. BP912412... CL4248Contig1 Show BP912412 Clone id YMU001_000018_G03 Library YMU01 Length 551 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000018_G03. Accession BP912412 Tissue type prothallium Developmental stag...tein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP912412|Adiantum capillus-veneris mR...NA, clone: YMU001_000018_G03. (551 letters) Database: uniprot_sprot.fasta 412,525 sequences; 148,809,765 tot

AcEST: BP912012 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000012_A06 542 Adiantum capillus-veneris mRNA. clone: YMU001_000012_A06. BP912012... CL2421Contig1 Show BP912012 Clone id YMU001_000012_A06 Library YMU01 Length 542 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000012_A06. Accession BP912012 Tissue type prothallium Developmental stag...rams, Nucleic Acids Res. 25:3389-3402. Query= BP912012|Adiantum capillus-veneris ...mRNA, clone: YMU001_000012_A06. (542 letters) Database: uniprot_sprot.fasta 412,525 sequences; 148,809,765 t

AcEST: BP912123 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000015_D05 496 Adiantum capillus-veneris mRNA. clone: YMU001_000015_D05. BP91212...3 CL498Contig1 Show BP912123 Clone id YMU001_000015_D05 Library YMU01 Length 496 Definition Adiantum cap...illus-veneris mRNA. clone: YMU001_000015_D05. Accession BP912123 Tissue type prothallium Developmental stage...n of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP91212...3|Adiantum capillus-veneris mRNA, clone: YMU001_000015_D05. (478 letters) Database: uniprot_sprot.fasta 412

AcEST: BP912512 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000019_D01 513 Adiantum capillus-veneris mRNA. clone: YMU001_000019_D01. BP912512... CL17Contig1 Show BP912512 Clone id YMU001_000019_D01 Library YMU01 Length 513 Definition Adiantum capi...llus-veneris mRNA. clone: YMU001_000019_D01. Accession BP912512 Tissue type prothallium Developmental stage ...earch programs, Nucleic Acids Res. 25:3389-3402. Query= BP912512|Adiantum capillus-veneris mRNA, clone: YMU0...01_000019_D01. (489 letters) Database: uniprot_sprot.fasta 412,525 sequences; 148,809,765 total letters Sear

AcEST: BP912129 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000015_D11 268 Adiantum capillus-veneris mRNA. clone: YMU001_000015_D11. BP91212...9 CL691Contig1 Show BP912129 Clone id YMU001_000015_D11 Library YMU01 Length 268 Definition Adiantum cap...illus-veneris mRNA. clone: YMU001_000015_D11. Accession BP912129 Tissue type prothallium Developmental stage...tabase search programs, Nucleic Acids Res. 25:3389-3402. Query= BP912129|Adiantum capillus-veneris mRNA, clo...ne: YMU001_000015_D11. (268 letters) Database: uniprot_sprot.fasta 412,525 sequences; 148,809,765 total lett

AcEST: BP917373 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000100_A08 270 Adiantum capillus-veneris mRNA. clone: YMU001_000100_A08. BP917373 CL2373...Contig1 Show BP917373 Clone id YMU001_000100_A08 Library YMU01 Length 270 Definition Adiantum ca...pillus-veneris mRNA. clone: YMU001_000100_A08. Accession BP917373 Tissue type prothallium Developmental stage - Contig ID CL2373...search programs, Nucleic Acids Res. 25:3389-3402. Query= BP917373|Adiantum capillus-veneris mRNA, clone: YMU...EGAVKHVGVLSS 206 K+ GC+S G SRHGES V KE H SS Sbjct: 473 KKEKGCSSPGSSRHGESHKGVSHTPI

Integrative device and process of oxidization, degassing, acidity adjustment of 1BP from APOR process

Energy Technology Data Exchange (ETDEWEB)

Zuo, Chen; Zheng, Weifang, E-mail: wfazh@ciae.ac.cn; Yan, Taihong; He, Hui; Li, Gaoliang; Chang, Shangwen; Li, Chuanbo; Yuan, Zhongwei

2016-02-15

Graphical abstract: Previous (left) and present (right) device of oxidation, degassing, acidity adjustment of 1BP. - Highlights: • We designed an integrative device and process. • The utilization efficiency of N{sub 2}O{sub 4} is increased significantly. • Our work results in considerable simplification of the device. • Process parameters are determined by experiments. - Abstract: Device and process of oxidization, degassing, acidity adjustment of 1BP (The Pu production feed from U/Pu separation section) from APOR process (Advanced Purex Process based on Organic Reductants) were improved through rational design and experiments. The device was simplified and the process parameters, such as feed position and flow ratio, were determined by experiments. Based on this new device and process, the reductants N,N-dimethylhydroxylamine (DMHAN) and methylhydrazine (MMH) in 1BP solution could be oxidized with much less N{sub 2}O{sub 4} consumption.

The Functional Role of TopBP1 in DNA Maintenance at Mitosis

DEFF Research Database (Denmark)

Pedersen, Rune Troelsgaard

When cells traverse mitosis, genome integrity of the emerging daughter cells is dependent on replication of the entire genome during the preceding S-phase and accurate chromosome segregation in mitosis. Replication stress may cause cells to enter mitosis with underreplicated loci, consisting...... can lead to anaphase bridges that impair accurate chromosome segregation. The recent decade featured many advances in our understanding of how cells cope with underreplicated loci in mitosis. A major advance was the description of ultra-fine anaphase bridges (UFBs), a class of anaphase bridges...... established Saccharomyces cerevisiae as a model organism to study anaphase bridges, and we identified Dpb11/TopBP1 as a novel UFB-associated protein in yeast and avian DT40 cells, respectively. TopBP1 localized to confined areas on replication-stress induced UFBs. Upon onset of mitosis we observed a burst...

AcEST: BP913939 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000038_B01 468 Adiantum capillus-veneris mRNA. clone: YMU001_000038_B01. BP913939 - Show BP913939...is mRNA. clone: YMU001_000038_B01. Accession BP913939 Tissue type prothallium Developmental stage - Contig I...Nucleic Acids Res. 25:3389-3402. Query= BP913939|Adiantum capillus-veneris mRNA, ... F member 3... 86 9e-17 sp|Q66H39|ABCF3_RAT ATP-binding cassette sub-family F member 3 O... 85 1e-16 sp|Q5R9...aracterized ABC transporter ATP-binding... 56 6e-08 sp|P63390|YHES_ECO57 Uncharacterized ABC transporter ATP

AcEST: BP912127 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000015_D09 582 Adiantum capillus-veneris mRNA. clone: YMU001_000015_D09. BP912127 - Show BP91212...is mRNA. clone: YMU001_000015_D09. Accession BP912127 Tissue type prothallium Developmental stage - Contig I...n database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP912127|Adiantum capillus-veneris mRNA,... clone: YMU001_000015_D09. (582 letters) Database: uniprot_sprot.fasta 412,525 sequences; 148,809,765 total ...p|P42825|DNAJ2_ARATH Chaperone protein dnaJ 2 OS=Arabidopsis th... 79 2e-14 sp|Q09912|PSI1_SCHPO Protein psi

Regulation of 4E-BP1 activity in the mammalian oocyte

Czech Academy of Sciences Publication Activity Database

Jansová, Denisa; Končická, Markéta; Tětková, Anna; Černá, Renata; Malík, Radek; del Llano, Edgar; Kubelka, Michal; Šušor, Andrej

2017-01-01

Roč. 16, č. 10 (2017), s. 927-939 ISSN 1538-4101 R&D Projects: GA ČR GA13-12291S; GA ČR GA15-22765S; GA MŠk EF15_003/0000460 Institutional support: RVO:67985904 ; RVO:68378050 Keywords : 4E-BP1 * CDK1 * cumulus cells Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 3.530, year: 2016

Interaction of CtBP with adenovirus E1A suppresses immortalization of primary epithelial cells and enhances virus replication during productive infection

Energy Technology Data Exchange (ETDEWEB)

Subramanian, T.; Zhao, Ling-jun; Chinnadurai, G., E-mail: chinnag@slu.edu

2013-09-01

Adenovirus E1A induces cell proliferation, oncogenic transformation and promotes viral replication through interaction with p300/CBP, TRRAP/p400 multi-protein complex and the retinoblastoma (pRb) family proteins through distinct domains in the E1A N-terminal region. The C-terminal region of E1A suppresses E1A/Ras co-transformation and interacts with FOXK1/K2, DYRK1A/1B/HAN11 and CtBP1/2 (CtBP) protein complexes. To specifically dissect the role of CtBP interaction with E1A, we engineered a mutation (DL→AS) within the CtBP-binding motif, PLDLS, and investigated the effect of the mutation on immortalization and Ras cooperative transformation of primary cells and viral replication. Our results suggest that CtBP–E1A interaction suppresses immortalization and Ras co-operative transformation of primary rodent epithelial cells without significantly influencing the tumorigenic activities of transformed cells in immunodeficient and immunocompetent animals. During productive infection, CtBP–E1A interaction enhances viral replication in human cells. Between the two CtBP family proteins, CtBP2 appears to restrict viral replication more than CtBP1 in human cells. - Highlights: • Adenovirus E1A C-terminal region suppresses E1A/Ras co-transformation. • This E1A region binds with FOXK, DYRK1/HAN11 and CtBP cellular protein complexes. • We found that E1A–CtBP interaction suppresses immortalization and transformation. • The interaction enhances viral replication in human cells.

Assembly of human C-terminal binding protein (CtBP) into tetramers.

Science.gov (United States)

Bellesis, Andrew G; Jecrois, Anne M; Hayes, Janelle A; Schiffer, Celia A; Royer, William E

2018-06-08

C-terminal binding protein 1 (CtBP1) and CtBP2 are transcriptional coregulators that repress numerous cellular processes, such as apoptosis, by binding transcription factors and recruiting chromatin-remodeling enzymes to gene promoters. The NAD(H)-linked oligomerization of human CtBP is coupled to its co-transcriptional activity, which is implicated in cancer progression. However, the biologically relevant level of CtBP assembly has not been firmly established; nor has the stereochemical arrangement of the subunits above that of a dimer. Here, multi-angle light scattering (MALS) data established the NAD + - and NADH-dependent assembly of CtBP1 and CtBP2 into tetramers. An examination of subunit interactions within CtBP1 and CtBP2 crystal lattices revealed that both share a very similar tetrameric arrangement resulting from assembly of two dimeric pairs, with specific interactions probably being sensitive to NAD(H) binding. Creating a series of mutants of both CtBP1 and CtBP2, we tested the hypothesis that the crystallographically observed interdimer pairing stabilizes the solution tetramer. MALS data confirmed that these mutants disrupt both CtBP1 and CtBP2 tetramers, with the dimer generally remaining intact, providing the first stereochemical models for tetrameric assemblies of CtBP1 and CtBP2. The crystal structure of a subtle destabilizing mutant suggested that small structural perturbations of the hinge region linking the substrate- and NAD-binding domains are sufficient to weaken the CtBP1 tetramer. These results strongly suggest that the tetramer is important in CtBP function, and the series of CtBP mutants reported here can be used to investigate the physiological role of the tetramer. © 2018 Bellesis et al.

BP volume reduction equipment

International Nuclear Information System (INIS)

Kitamura, Yoshinori; Muroo, Yoji; Hamanaka, Isao

2003-01-01

A new type of burnable poison (BP) volume reduction system is currently being developed. Many BP rods, a subcomponent of spent fuel assemblies are discharged from nuclear power reactors. This new system reduces the overall volume of BP rods. The main system consists of BP rod cutting equipment, equipment for the recovery of BP cut pieces, and special transport equipment for the cut rods. The equipment is all operated by hydraulic press cylinders in water to reduce operator exposure to radioactivity. (author)

Interaction of HmC1q with leech microglial cells: involvement of C1qBP-related molecule in the induction of cell chemotaxis

Directory of Open Access Journals (Sweden)

Tahtouh Muriel

2012-02-01

Full Text Available Abstract Background In invertebrates, the medicinal leech is considered to be an interesting and appropriate model to study neuroimmune mechanisms. Indeed, this non-vertebrate animal can restore normal function of its central nervous system (CNS after injury. Microglia accumulation at the damage site has been shown to be required for axon sprouting and for efficient regeneration. We characterized HmC1q as a novel chemotactic factor for leech microglial cell recruitment. In mammals, a C1q-binding protein (C1qBP alias gC1qR, which interacts with the globular head of C1q, has been reported to participate in C1q-mediated chemotaxis of blood immune cells. In this study, we evaluated the chemotactic activities of a recombinant form of HmC1q and its interaction with a newly characterized leech C1qBP that acts as its potential ligand. Methods Recombinant HmC1q (rHmC1q was produced in the yeast Pichia pastoris. Chemotaxis assays were performed to investigate rHmC1q-dependent microglia migration. The involvement of a C1qBP-related molecule in this chemotaxis mechanism was assessed by flow cytometry and with affinity purification experiments. The cellular localization of C1qBP mRNA and protein in leech was investigated using immunohistochemistry and in situ hybridization techniques. Results rHmC1q-stimulated microglia migrate in a dose-dependent manner. This rHmC1q-induced chemotaxis was reduced when cells were preincubated with either anti-HmC1q or anti-human C1qBP antibodies. A C1qBP-related molecule was characterized in leech microglia. Conclusions A previous study showed that recruitment of microglia is observed after HmC1q release at the cut end of axons. Here, we demonstrate that rHmC1q-dependent chemotaxis might be driven via a HmC1q-binding protein located on the microglial cell surface. Taken together, these results highlight the importance of the interaction between C1q and C1qBP in microglial activation leading to nerve repair in the medicinal

Interaction of HmC1q with leech microglial cells: involvement of C1qBP-related molecule in the induction of cell chemotaxis.

Science.gov (United States)

Tahtouh, Muriel; Garçon-Bocquet, Annelise; Croq, Françoise; Vizioli, Jacopo; Sautière, Pierre-Eric; Van Camp, Christelle; Salzet, Michel; Nagnan-le Meillour, Patricia; Pestel, Joël; Lefebvre, Christophe

2012-02-22

In invertebrates, the medicinal leech is considered to be an interesting and appropriate model to study neuroimmune mechanisms. Indeed, this non-vertebrate animal can restore normal function of its central nervous system (CNS) after injury. Microglia accumulation at the damage site has been shown to be required for axon sprouting and for efficient regeneration. We characterized HmC1q as a novel chemotactic factor for leech microglial cell recruitment. In mammals, a C1q-binding protein (C1qBP alias gC1qR), which interacts with the globular head of C1q, has been reported to participate in C1q-mediated chemotaxis of blood immune cells. In this study, we evaluated the chemotactic activities of a recombinant form of HmC1q and its interaction with a newly characterized leech C1qBP that acts as its potential ligand. Recombinant HmC1q (rHmC1q) was produced in the yeast Pichia pastoris. Chemotaxis assays were performed to investigate rHmC1q-dependent microglia migration. The involvement of a C1qBP-related molecule in this chemotaxis mechanism was assessed by flow cytometry and with affinity purification experiments. The cellular localization of C1qBP mRNA and protein in leech was investigated using immunohistochemistry and in situ hybridization techniques. rHmC1q-stimulated microglia migrate in a dose-dependent manner. This rHmC1q-induced chemotaxis was reduced when cells were preincubated with either anti-HmC1q or anti-human C1qBP antibodies. A C1qBP-related molecule was characterized in leech microglia. A previous study showed that recruitment of microglia is observed after HmC1q release at the cut end of axons. Here, we demonstrate that rHmC1q-dependent chemotaxis might be driven via a HmC1q-binding protein located on the microglial cell surface. Taken together, these results highlight the importance of the interaction between C1q and C1qBP in microglial activation leading to nerve repair in the medicinal leech.

Structures of the Mycobacterium tuberculosis GlpX protein (class II fructose-1,6-bisphosphatase): implications for the active oligomeric state, catalytic mechanism and citrate inhibition.

Science.gov (United States)

Wolf, Nina M; Gutka, Hiten J; Movahedzadeh, Farahnaz; Abad-Zapatero, Celerino

2018-04-01

The crystal structures of native class II fructose-1,6-bisphosphatase (FBPaseII) from Mycobacterium tuberculosis at 2.6 Å resolution and two active-site protein variants are presented. The variants were complexed with the reaction product fructose 6-phosphate (F6P). The Thr84Ala mutant is inactive, while the Thr84Ser mutant has a lower catalytic activity. The structures reveal the presence of a 222 tetramer, similar to those described for fructose-1,6/sedoheptulose-1,7-bisphosphatase from Synechocystis (strain 6803) as well as the equivalent enzyme from Thermosynechococcus elongatus. This homotetramer corresponds to a homologous oligomer that is present but not described in the crystal structure of FBPaseII from Escherichia coli and is probably conserved in all FBPaseIIs. The constellation of amino-acid residues in the active site of FBPaseII from M. tuberculosis (MtFBPaseII) is conserved and is analogous to that described previously for the E. coli enzyme. Moreover, the structure of the active site of the partially active (Thr84Ser) variant and the analysis of the kinetics are consistent with the previously proposed catalytic mechanism. The presence of metabolites in the crystallization medium (for example citrate and malonate) and in the corresponding crystal structures of MtFBPaseII, combined with their observed inhibitory effect, could suggest the existence of an uncharacterized inhibition of this class of enzymes besides the allosteric inhibition by adenosine monophosphate observed for the Synechocystis enzyme. The structural and functional insights derived from the structure of MtFBPaseII will provide critical information for the design of lead inhibitors, which will be used to validate this target for future chemical intervention.

Pathway-Enriched Gene Signature Associated with 53BP1 Response to PARP Inhibition in Triple-Negative Breast Cancer.

Science.gov (United States)

Hassan, Saima; Esch, Amanda; Liby, Tiera; Gray, Joe W; Heiser, Laura M

2017-12-01

Effective treatment of patients with triple-negative (ER-negative, PR-negative, HER2-negative) breast cancer remains a challenge. Although PARP inhibitors are being evaluated in clinical trials, biomarkers are needed to identify patients who will most benefit from anti-PARP therapy. We determined the responses of three PARP inhibitors (veliparib, olaparib, and talazoparib) in a panel of eight triple-negative breast cancer cell lines. Therapeutic responses and cellular phenotypes were elucidated using high-content imaging and quantitative immunofluorescence to assess markers of DNA damage (53BP1) and apoptosis (cleaved PARP). We determined the pharmacodynamic changes as percentage of cells positive for 53BP1, mean number of 53BP1 foci per cell, and percentage of cells positive for cleaved PARP. Inspired by traditional dose-response measures of cell viability, an EC 50 value was calculated for each cellular phenotype and each PARP inhibitor. The EC 50 values for both 53BP1 metrics strongly correlated with IC 50 values for each PARP inhibitor. Pathway enrichment analysis identified a set of DNA repair and cell cycle-associated genes that were associated with 53BP1 response following PARP inhibition. The overall accuracy of our 63 gene set in predicting response to olaparib in seven breast cancer patient-derived xenograft tumors was 86%. In triple-negative breast cancer patients who had not received anti-PARP therapy, the predicted response rate of our gene signature was 45%. These results indicate that 53BP1 is a biomarker of response to anti-PARP therapy in the laboratory, and our DNA damage response gene signature may be used to identify patients who are most likely to respond to PARP inhibition. Mol Cancer Ther; 16(12); 2892-901. ©2017 AACR . ©2017 American Association for Cancer Research.

Mechanism of Androgen Receptor Corepression by CKβBP2/CRIF1, a Multifunctional Transcription Factor Coregulator Expressed in Prostate Cancer

OpenAIRE

Tan, Jiann-an; Bai, Suxia; Grossman, Gail; Titus, Mark A.; Ford, O. Harris; Pop, Elena A.; Smith, Gary J.; Mohler, James L.; Wilson, Elizabeth M.; French, Frank S.

2013-01-01

The transcription factor coregulator Casein kinase IIβbinding protein 2 or CR6-interacting factor 1 (CKβBP2/CRIF1) binds the androgen receptor (AR) in prostate cancer cells and in response to dihydrotestosterone localizes with AR on the prostate-specific antigen gene enhancer, but does not bind DNA suggesting CKβBP2/CRIF1 localization in chromatin is determined by AR. In this study we show also that CKβBP2/CRIF1 inhibits wild-type AR and AR N-terminal transcriptional activity, binds to the AR...

The Transcriptomes of Xiphinema index and Longidorus elongatus Suggest Independent Acquisition of Some Plant Parasitism Genes by Horizontal Gene Transfer in Early-Branching Nematodes

Science.gov (United States)

Danchin, Etienne G.J.; Perfus-Barbeoch, Laetitia; Rancurel, Corinne; Thorpe, Peter; Da Rocha, Martine; Bajew, Simon; Neilson, Roy; Sokolova (Guzeeva), Elena; Da Silva, Corinne; Guy, Julie; Labadie, Karine; Esmenjaud, Daniel; Helder, Johannes; Jones, John T.

2017-01-01

Nematodes have evolved the ability to parasitize plants on at least four independent occasions, with plant parasites present in Clades 1, 2, 10 and 12 of the phylum. In the case of Clades 10 and 12, horizontal gene transfer of plant cell wall degrading enzymes from bacteria and fungi has been implicated in the evolution of plant parasitism. We have used ribonucleic acid sequencing (RNAseq) to generate reference transcriptomes for two economically important nematode species, Xiphinema index and Longidorus elongatus, representative of two genera within the early-branching Clade 2 of the phylum Nematoda. We used a transcriptome-wide analysis to identify putative horizontal gene transfer events. This represents the first in-depth transcriptome analysis from any plant-parasitic nematode of this clade. For each species, we assembled ~30 million Illumina reads into a reference transcriptome. We identified 62 and 104 transcripts, from X. index and L. elongatus, respectively, that were putatively acquired via horizontal gene transfer. By cross-referencing horizontal gene transfer prediction with a phylum-wide analysis of Pfam domains, we identified Clade 2-specific events. Of these, a GH12 cellulase from X. index was analysed phylogenetically and biochemically, revealing a likely bacterial origin and canonical enzymatic function. Horizontal gene transfer was previously shown to be a phenomenon that has contributed to the evolution of plant parasitism among nematodes. Our findings underline the importance and the extensiveness of this phenomenon in the evolution of plant-parasitic life styles in this speciose and widespread animal phylum. PMID:29065523

The Transcriptomes of Xiphinema index and Longidorus elongatus Suggest Independent Acquisition of Some Plant Parasitism Genes by Horizontal Gene Transfer in Early-Branching Nematodes.

Science.gov (United States)

Danchin, Etienne G J; Perfus-Barbeoch, Laetitia; Rancurel, Corinne; Thorpe, Peter; Da Rocha, Martine; Bajew, Simon; Neilson, Roy; Guzeeva, Elena Sokolova; Da Silva, Corinne; Guy, Julie; Labadie, Karine; Esmenjaud, Daniel; Helder, Johannes; Jones, John T; den Akker, Sebastian Eves-van

2017-10-23

Nematodes have evolved the ability to parasitize plants on at least four independent occasions, with plant parasites present in Clades 1, 2, 10 and 12 of the phylum. In the case of Clades 10 and 12, horizontal gene transfer of plant cell wall degrading enzymes from bacteria and fungi has been implicated in the evolution of plant parasitism. We have used ribonucleic acid sequencing (RNAseq) to generate reference transcriptomes for two economically important nematode species, Xiphinema index and Longidorus elongatus , representative of two genera within the early-branching Clade 2 of the phylum Nematoda. We used a transcriptome-wide analysis to identify putative horizontal gene transfer events. This represents the first in-depth transcriptome analysis from any plant-parasitic nematode of this clade. For each species, we assembled ~30 million Illumina reads into a reference transcriptome. We identified 62 and 104 transcripts, from X. index and L. elongatus , respectively, that were putatively acquired via horizontal gene transfer. By cross-referencing horizontal gene transfer prediction with a phylum-wide analysis of Pfam domains, we identified Clade 2-specific events. Of these, a GH12 cellulase from X. index was analysed phylogenetically and biochemically, revealing a likely bacterial origin and canonical enzymatic function. Horizontal gene transfer was previously shown to be a phenomenon that has contributed to the evolution of plant parasitism among nematodes. Our findings underline the importance and the extensiveness of this phenomenon in the evolution of plant-parasitic life styles in this speciose and widespread animal phylum.

The Transcriptomes of Xiphinema index and Longidorus elongatus Suggest Independent Acquisition of Some Plant Parasitism Genes by Horizontal Gene Transfer in Early-Branching Nematodes

Directory of Open Access Journals (Sweden)

Etienne G.J. Danchin

2017-10-01

Full Text Available Nematodes have evolved the ability to parasitize plants on at least four independent occasions, with plant parasites present in Clades 1, 2, 10 and 12 of the phylum. In the case of Clades 10 and 12, horizontal gene transfer of plant cell wall degrading enzymes from bacteria and fungi has been implicated in the evolution of plant parasitism. We have used ribonucleic acid sequencing (RNAseq to generate reference transcriptomes for two economically important nematode species, Xiphinema index and Longidorus elongatus, representative of two genera within the early-branching Clade 2 of the phylum Nematoda. We used a transcriptome-wide analysis to identify putative horizontal gene transfer events. This represents the first in-depth transcriptome analysis from any plant-parasitic nematode of this clade. For each species, we assembled ~30 million Illumina reads into a reference transcriptome. We identified 62 and 104 transcripts, from X. index and L. elongatus, respectively, that were putatively acquired via horizontal gene transfer. By cross-referencing horizontal gene transfer prediction with a phylum-wide analysis of Pfam domains, we identified Clade 2-specific events. Of these, a GH12 cellulase from X. index was analysed phylogenetically and biochemically, revealing a likely bacterial origin and canonical enzymatic function. Horizontal gene transfer was previously shown to be a phenomenon that has contributed to the evolution of plant parasitism among nematodes. Our findings underline the importance and the extensiveness of this phenomenon in the evolution of plant-parasitic life styles in this speciose and widespread animal phylum.

A Damage-Independent Role for 53BP1 that Impacts Break Order and Igh Architecture during Class Switch Recombination

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Pedro P. Rocha

2016-06-01

Full Text Available During class switch recombination (CSR, B cells replace the Igh Cμ or δ exons with another downstream constant region exon (CH, altering the antibody isotype. CSR occurs through the introduction of AID-mediated double-strand breaks (DSBs in switch regions and subsequent ligation of broken ends. Here, we developed an assay to investigate the dynamics of DSB formation in individual cells. We demonstrate that the upstream switch region Sμ is first targeted during recombination and that the mechanism underlying this control relies on 53BP1. Surprisingly, regulation of break order occurs through residual binding of 53BP1 to chromatin before the introduction of damage and independent of its established role in DNA repair. Using chromosome conformation capture, we show that 53BP1 mediates changes in chromatin architecture that affect break order. Finally, our results explain how changes in Igh architecture in the absence of 53BP1 could promote inversional rearrangements that compromise CSR.

Dpb11/TopBP1 contributes to genomicstability via homologous recombinationand checkpoint signaling

DEFF Research Database (Denmark)

Germann, Susanne Manuela

for recruitment. Also, the chicken homologue TopBP1 colocalizes with RPA1 as well as Rad51 when DNA damage is induced. Previously, dpb11 mutants have been shown to be sensitive to DNA-damaging agents that cause DSBs, DNA alkylation and stalled replication forks. Interestingly, we found the point mutants dpb11-PF...

Is Monoglucosyldiacylglycerol a Precursor to Monogalactosyldiacylglycerol in All Cyanobacteria?

Science.gov (United States)

Sato, Naoki

2015-10-01

Monogalactosyldiacylglycerol (MGDG) is ubiquitous in the photosynthetic membranes of cyanobacteria and chloroplasts. It is synthesized by galactosylation of diacylglycerol (DAG) in the chloroplasts, whereas it is produced by epimerization of monoglucosyldiacylglycerol (GlcDG) in at least several cyanobacteria that have been analyzed such as Synechocystis sp. PCC 6803. A previous study, however, showed that the mgdE gene encoding the epimerase is absent in some cyanobacteria such as Gloeobacter violaceus, Thermosynechococcus elongatus and Acaryochloris marina. In addition, the N-terminal 'fatty acid hydroxylase' domain is lacking in the MgdE protein of Prochlorococcus marinus. These problems may cast doubt upon the general (or exclusive) role of MgdE in the epimerization of GlcDG to MGDG in cyanobacteria. In addition, GlcDG is usually present at a very low level, and the structural determination of endogenous GlcDG has not been accomplished with cyanobacterial samples. In this study, I determined the structure of GlcDG from Anabaena variabilis by (1)H- and (13)C-nuclear magnetic resonance (NMR) spectroscopy. I then showed that G. violaceus, T. elongatus, A. marina and P. marinus contain GlcDG. In all cases, GlcDG consisted of fewer unsaturated molecular species than MGDG, providing further evidence that GlcDG is a precursor to MGDG. The conversion of GlcDG to MGDG was also demonstrated by radiolabeling and chase experiments in G. violaceus and P. marinus. These results demonstrate that all the analyzed cyanobacteria contain GlcDG, which is converted to MGDG, and suggest that an alternative epimerase is required for MGDG synthesis in these cyanobacteria. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The strontium inorganic mutant of the water oxidizing center (CaMn4O5) of PSII improves WOC efficiency but slows electron flux through the terminal acceptors.

Science.gov (United States)

Gates, Colin; Ananyev, Gennady; Dismukes, G Charles

2016-09-01

Herein we extend prior studies of biosynthetic strontium replacement of calcium in PSII-WOC core particles to characterize whole cells. Previous studies of Thermosynechococcus elongatus found a lower rate of light-saturated O2 from isolated PSII-WOC(Sr) cores and 5-8× slower rate of oxygen release. We find similar properties in whole cells, and show it is due to a 20% larger Arrhenius activation barrier for O2 evolution. Cellular adaptation to the sluggish PSII-WOC(Sr) cycle occurs in which flux through the QAQB acceptor gate becomes limiting for turnover rate in vivo. Benzoquinone derivatives that bind to QB site remove this kinetic chokepoint yielding 31% greater O2 quantum yield (QY) of PSII-WOC(Sr) vs. PSII-WOC(Ca). QY and efficiency of the WOC(Sr) catalytic cycle are greatly improved at low light flux, due to fewer misses and backward transitions and 3-fold longer lifetime of the unstable S3 state, attributed to greater thermodynamic stabilization of the WOC(Sr) relative to the photoactive tyrosine YZ. More linear and less cyclic electron flow through PSII occurs per PSII-WOC(Sr). The organismal response to the more active PSII centers in Sr-grown cells at 45°C is to lower the number of active PSII-WOC per Chl, producing comparable oxygen and energy per cell. We conclude that redox and protonic energy fluxes created by PSII are primary determinants for optimal growth rate of T. elongatus. We further conclude that the (Sr-favored) intermediate-spin S=5/2 form of the S2 state is the active form in the catalytic cycle relative to the low-spin S=1/2 form. Copyright © 2016 Elsevier B.V. All rights reserved.

The predictive value of 53BP1 and BRCA1 mRNA expression in advanced non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy

Science.gov (United States)

Bonanno, Laura; Costa, Carlota; Majem, Margarita; Sanchez, Jose Javier; Gimenez-Capitan, Ana; Rodriguez, Ignacio; Vergenegre, Alain; Massuti, Bartomeu; Favaretto, Adolfo; Rugge, Massimo; Pallares, Cinta; Taron, Miquel; Rosell, Rafael

2013-01-01

Platinum-based chemotherapy is the standard first-line treatment for non-oncogene-addicted non-small cell lung cancers (NSCLCs) and the analysis of multiple DNA repair genes could improve current models for predicting chemosensitivity. We investigated the potential predictive role of components of the 53BP1 pathway in conjunction with BRCA1. The mRNA expression of BRCA1, MDC1, CASPASE3, UBC13, RNF8, 53BP1, PIAS4, UBC9 and MMSET was analyzed by real-time PCR in 115 advanced NSCLC patients treated with first-line platinum-based chemotherapy. Patients expressing low levels of both BRCA1 and 53BP1 obtained a median progression-free survival of 10.3 months and overall survival of 19.3 months, while among those with low BRCA1 and high 53BP1 progression-free survival was 5.9 months (P <0.0001) and overall survival was 8.2 months (P=0.001). The expression of 53BP1 refines BRCA1-based predictive modeling to identify patients most likely to benefit from platinum-based chemotherapy. PMID:24197907

Validation of the Welch Allyn SureBP (inflation) and StepBP (deflation) algorithms by AAMI standard testing and BHS data analysis.

Science.gov (United States)

Alpert, Bruce S

2011-04-01

We evaluated two new Welch Allyn automated blood pressure (BP) algorithms. The first, SureBP, estimates BP during cuff inflation; the second, StepBP, does so during deflation. We followed the American National Standards Institute/Association for the Advancement of Medical Instrumentation SP10:2006 standard for testing and data analysis. The data were also analyzed using the British Hypertension Society analysis strategy. We tested children, adolescents, and adults. The requirements of the American National Standards Institute/Association for the Advancement of Medical Instrumentation SP10:2006 standard were fulfilled with respect to BP levels, arm sizes, and ages. Association for the Advancement of Medical Instrumentation SP10 Method 1 data analysis was used. The mean±standard deviation for the device readings compared with auscultation by paired, trained, blinded observers in the SureBP mode were -2.14±7.44 mmHg for systolic BP (SBP) and -0.55±5.98 mmHg for diastolic BP (DBP). In the StepBP mode, the differences were -3.61±6.30 mmHg for SBP and -2.03±5.30 mmHg for DBP. Both algorithms achieved an A grade for both SBP and DBP by British Hypertension Society analysis. The SureBP inflation-based algorithm will be available in many new-generation Welch Allyn monitors. Its use will reduce the time it takes to estimate BP in critical patient care circumstances. The device will not need to inflate to excessive suprasystolic BPs to obtain the SBP values. Deflation is rapid once SBP has been determined, thus reducing the total time of cuff inflation and reducing patient discomfort. If the SureBP fails to obtain a BP value, the StepBP algorithm is activated to estimate BP by traditional deflation methodology.

CacyBP/SIP promotes the proliferation of colon cancer cells.

Directory of Open Access Journals (Sweden)

Huihong Zhai

Full Text Available CacyBP/SIP is a component of the ubiquitin pathway and is overexpressed in several transformed tumor tissues, including colon cancer, which is one of the most common cancers worldwide. It is unknown whether CacyBP/SIP promotes the proliferation of colon cancer cells. This study examined the expression level, subcellular localization, and binding activity of CacyBP/SIP in human colon cancer cells in the presence and absence of the hormone gastrin. We found that CacyBP/SIP was expressed in a high percentage of colon cancer cells, but not in normal colonic surface epithelium. CacyBP/SIP promoted the cell proliferation of colon cancer cells under both basal and gastrin stimulated conditions as shown by knockdown studies. Gastrin stimulation triggered the translocation of CacyBP/SIP to the nucleus, and enhanced interaction between CacyBP/SIP and SKP1, a key component of ubiquitination pathway which further mediated the proteasome-dependent degradation of p27kip1 protein. The gastrin induced reduction in p27kip1 was prevented when cells were treated with the proteasome inhibitor MG132. These results suggest that CacyBP/SIP may be promoting growth of colon cancer cells by enhancing ubiquitin-mediated degradation of p27kip1.

The study of desiccation-tolerance in drying leaves of the desiccation-tolerant grass Sporobolus elongatus and the desiccation-sensitive grass Sporobolus pyramidalis.

Science.gov (United States)

Ghasempour, Hamid Reza; Kianian, Jahanbakheshe

2007-03-01

Hydrated leaves of the resurrection grass Sporobolus elongatus are not desiccation tolerant (DT), but moderate to severe drought stress can induce their DT with the leaves remain attach to drying intact plants. In vivo protein synthesis was studied with SDS-page of extracts of leaves of intact drying plants of S. elongatus (a desiccation-Tolerant grass (DT)) and S. pyramidalis (a desiccation-sensitive species (DS)). Free proline increased in drying leaves. Soluble sugar contents also increased with drying but were less than fully hydrated leaves at 8% RWC. Total protein also showed an increase with an exception at 8% RWC which showed a decrease. SDS-page of extracts of drying leaves of both DT and DS plants were studied as relative water contents (RWC) decreased. In first phase, DT species at 58% RWC (80-51% RWC range), two proteins increased in contents. In the second phase, at 8% (35-4% RWC range) two new bands increased and two bands decreased. In leaves of DS species some bands decreased as drying progressed. Also, as drying advanced free proline increased in DT species. Total protein increased as drying increased but at 8% RWC decreased. All data of results are consistent with current views about studied factors and their roles during drying and induction of desiccation tolerance in DT plants.

Functional interaction between type III-secreted protein IncA of Chlamydophila psittaci and human G3BP1.

Science.gov (United States)

Borth, Nicole; Litsche, Katrin; Franke, Claudia; Sachse, Konrad; Saluz, Hans Peter; Hänel, Frank

2011-01-31

Chlamydophila (Cp.) psittaci, the causative agent of psittacosis in birds and humans, is the most important zoonotic pathogen of the family Chlamydiaceae. These obligate intracellular bacteria are distinguished by a unique biphasic developmental cycle, which includes proliferation in a membrane-bound compartment termed inclusion. All Chlamydiaceae spp. possess a coding capacity for core components of a Type III secretion apparatus, which mediates specific delivery of anti-host effector proteins either into the chlamydial inclusion membrane or into the cytoplasm of target eukaryotic cells. Here we describe the interaction between Type III-secreted protein IncA of Cp. psittaci and host protein G3BP1 in a yeast two-hybrid system. In GST-pull down and co-immunoprecipitation experiments both in vitro and in vivo interaction between full-length IncA and G3BP1 were shown. Using fluorescence microscopy, the localization of G3BP1 near the inclusion membrane of Cp. psittaci-infected Hep-2 cells was demonstrated. Notably, infection of Hep-2 cells with Cp. psittaci and overexpression of IncA in HEK293 cells led to a decrease in c-Myc protein concentration. This effect could be ascribed to the interaction between IncA and G3BP1 since overexpression of an IncA mutant construct disabled to interact with G3BP1 failed to reduce c-Myc concentration. We hypothesize that lowering the host cell c-Myc protein concentration may be part of a strategy employed by Cp. psittaci to avoid apoptosis and scale down host cell proliferation.

A novel 5-bp deletion in Clarin 1 in a family with Usher syndrome.

Science.gov (United States)

Akoury, Elie; El Zir, Elie; Mansour, Ahmad; Mégarbané, André; Majewski, Jacek; Slim, Rima

2011-11-01

To identify the genetic defect in a Lebanese family with two sibs diagnosed with Usher Syndrome. Exome capture and sequencing were performed on DNA from one affected member using Agilent in solution bead capture, followed by Illumina sequencing. This analysis revealed the presence of a novel homozygous 5-bp deletion, in Clarin 1 (CLRN1), a known gene responsible for Usher syndrome type III. The deletion is inherited from both parents and segregates with the disease phenotype in the family. The 5-bp deletion, c.301_305delGTCAT, p.Val101SerfsX27, is predicted to result in a frameshift and protein truncation after 27 amino acids. Sequencing all the coding regions of the CLRN1 gene in the proband did not reveal any other mutation or variant. Here we describe a novel deletion in CLRN1. Our data support previously reported intra familial variability in the clinical features of Usher syndrome type I and III.

Structural insights into the light-driven auto-assembly process of the water-oxidizing Mn4CaO5-cluster in photosystem II.

Science.gov (United States)

Zhang, Miao; Bommer, Martin; Chatterjee, Ruchira; Hussein, Rana; Yano, Junko; Dau, Holger; Kern, Jan; Dobbek, Holger; Zouni, Athina

2017-07-18

In plants, algae and cyanobacteria, Photosystem II (PSII) catalyzes the light-driven splitting of water at a protein-bound Mn 4 CaO 5 -cluster, the water-oxidizing complex (WOC). In the photosynthetic organisms, the light-driven formation of the WOC from dissolved metal ions is a key process because it is essential in both initial activation and continuous repair of PSII. Structural information is required for understanding of this chaperone-free metal-cluster assembly. For the first time, we obtained a structure of PSII from Thermosynechococcus elongatus without the Mn 4 CaO 5 -cluster. Surprisingly, cluster-removal leaves the positions of all coordinating amino acid residues and most nearby water molecules largely unaffected, resulting in a pre-organized ligand shell for kinetically competent and error-free photo-assembly of the Mn 4 CaO 5 -cluster. First experiments initiating (i) partial disassembly and (ii) partial re-assembly after complete depletion of the Mn 4 CaO 5 -cluster agree with a specific bi-manganese cluster, likely a di-µ-oxo bridged pair of Mn(III) ions, as an assembly intermediate.

A Damage-Independent Role for 53BP1 that Impacts Break Order and Igh Architecture during Class Switch Recombination.

Science.gov (United States)

Rocha, Pedro P; Raviram, Ramya; Fu, Yi; Kim, JungHyun; Luo, Vincent M; Aljoufi, Arafat; Swanzey, Emily; Pasquarella, Alessandra; Balestrini, Alessia; Miraldi, Emily R; Bonneau, Richard; Petrini, John; Schotta, Gunnar; Skok, Jane A

2016-06-28

During class switch recombination (CSR), B cells replace the Igh Cμ or δ exons with another downstream constant region exon (CH), altering the antibody isotype. CSR occurs through the introduction of AID-mediated double-strand breaks (DSBs) in switch regions and subsequent ligation of broken ends. Here, we developed an assay to investigate the dynamics of DSB formation in individual cells. We demonstrate that the upstream switch region Sμ is first targeted during recombination and that the mechanism underlying this control relies on 53BP1. Surprisingly, regulation of break order occurs through residual binding of 53BP1 to chromatin before the introduction of damage and independent of its established role in DNA repair. Using chromosome conformation capture, we show that 53BP1 mediates changes in chromatin architecture that affect break order. Finally, our results explain how changes in Igh architecture in the absence of 53BP1 could promote inversional rearrangements that compromise CSR. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Radiosensitivity in breast cancer assessed by the histone γ-H2AX and 53BP1 foci

International Nuclear Information System (INIS)

Djuzenova, Cholpon S; Elsner, Ines; Katzer, Astrid; Worschech, Eike; Distel, Luitpold V; Flentje, Michael; Polat, Bülent

2013-01-01

High expression of constitutive histone γ-H2AX, a sensitive marker of DNA damage, might be indicative of defective DNA repair pathway or genomic instability. 53BP1 (p53-binding protein 1) is a conserved checkpoint protein with properties of a DNA double-strand breaks sensor. This study explores the relationship between the clinical radiosensitivity of tumor patients and the expression/induction of γ-H2AX and 53BP1 in vitro. Using immunostaining, we assessed spontaneous and radiation-induced foci of γ-H2AX and 53 BP1 in peripheral blood mononuclear cells derived from unselected breast cancer (BC) patients (n=57) undergoing radiotherapy (RT). Cells from apparently healthy donors (n=12) served as references. Non-irradiated cells from controls and unselected BC patients exhibited similar baseline levels of DNA damage assessed by γ-H2AX and 53BP1 foci. At the same time, the γ-H2AX assay of in vitro irradiated cells revealed significant differences between the control group and the group of unselected BC patients with respect to the initial (0.5 Gy, 30 min) and residual (2 Gy, 24 h post-radiation) DNA damage. The numbers of 53BP1 foci analyzed in 35 BC patients were significantly higher than in controls only in case of residual DNA damage. A weak correlation was found between residual foci of both proteins tested. In addition, cells from cancer patients with an adverse acute skin reaction (grade 3) to RT showed significantly increased radiation-induced γ-H2AX foci and their protracted disappearance compared to the group of BC patients with normal skin reaction (grade 0–1). The mean number of γ-H2AX foci after 5 clinical fractions was significantly higher than that before RT, especially in clinically radiosensitive patients. The γ-H2AX assay may have potential for screening individual radiosensitivity of breast cancer patients.

Induction of metallothionein(s) in organ-cultured duodenum: relationship to 1α,25-(OH)2-D3-induced CaBP synthesis

International Nuclear Information System (INIS)

Corradino, R.A.; Fullmer, C.S.; Frelier, E.; Maxwell, S.

1979-01-01

The embryonic chick duodenum contains no vitamin D-induced, calcium-binding protein (CaBP). However, when maintained in organ culture, the duodenum responds to 1α,25-(OH) 2 -D 3 in the culture medium by de novo synthesis of CaBP. Studies with this system have provided evidence that CaBP is directly involved in calcium transport at least at the mucosal surface. The present paper extends previous observations on the effects of the extremely toxic environmental pollutant, cadmium. Cadmium was found to inhibit 1α,25-(OH) 2 -D 3 -mediated responses in the organ-cultured duodenum, i.e., CaBP biosynthesis and 45 Ca uptake at the mucosal surface. Cadmium also stimulated concomitent production of a specific metallothionein (MT). Zinc had similar actions in inhibiting CaBP and stimulating Mt biosynthesis

A 50 bp deletion in the SOD1 promoter lowers enzyme expression but is not associated with ALS in Sweden.

Science.gov (United States)

Ingre, Caroline; Wuolikainen, Anna; Marklund, Stefan L; Birve, Anna; Press, Rayomand; Andersen, Peter M

2016-01-01

Mutations in the superoxide dismutase (SOD1) gene have been linked to amyotrophic lateral sclerosis (ALS). A 50 base pair (bp) deletion of SOD1 has been suggested to reduce transcription and to be associated with later disease onset in ALS. This study was aimed to reveal if the 50 bp deletion influenced SOD1 enzymatic activity, occurrence and phenotype of the disease in a Swedish ALS/control cohort. Blood samples from 512 Swedish ALS patients and 354 Swedish controls without coding SOD1 mutations were analysed for the 50 bp deletion allele. The enzymatic activity of SOD1 in erythrocytes was analysed and genotype-phenotype correlations were assessed. Results demonstrated that the genotype frequencies of the 50 bp deletion were all found to be in Hardy-Weinberg equilibrium. No significant differences were found for age of onset, disease duration or site of onset. SOD1 enzymatic activity showed a statistically significant decreasing trend in the control group, in which the allele was associated with a 5% reduction in SOD1 activity. The results suggest that the 50 bp deletion has a moderate reducing effect on SOD1 synthesis. No modulating effects, however, were found on ALS onset, phenotype and survival in the Swedish population.

Association of a Chromosomal Rearrangement Event with Mouse Posterior Polymorphous Corneal Dystrophy and Alterations in Csrp2bp, Dzank1, and Ovol2 Gene Expression.

Directory of Open Access Journals (Sweden)

Anna L Shen

Full Text Available We have previously described a mouse model of human posterior polymorphous corneal dystrophy (PPCD and localized the causative mutation to a 6.2 Mbp region of chromosome 2, termed Ppcd1. We now show that the gene rearrangement linked to mouse Ppcd1 is a 3.9 Mbp chromosomal inversion flanked by 81 Kbp and 542 bp deletions. This recombination event leads to deletion of Csrp2bp Exons 8 through 11, Dzank1 Exons 20 and 21, and the pseudogene Znf133. In addition, we identified translocation of novel downstream sequences to positions adjacent to Csrp2bp Exon 7 and Dzank1 Exon 20. Twelve novel fusion transcripts involving Csrp2bp or Dzank1 linked to downstream sequences have been identified. Eight are expressed at detectable levels in PPCD1 but not wildtype eyes. Upregulation of two Csrp2bp fusion transcripts, as well as upregulation of the adjacent gene, Ovol2, was observed. Absence of the PPCD1 phenotype in animals haploinsufficient for Csrp2bp or both Csrp2bp and Dzank1 rules out haploinsufficiency of these genes as a cause of mouse PPCD1. Complementation experiments confirm that PPCD1 embryonic lethality is due to disruption of Csrp2bp expression. The ocular expression pattern of Csrp2bp is consistent with a role for this protein in corneal development and pathogenesis of PPCD1.

Crystal structures of the human G3BP1 NTF2-like domain visualize FxFG Nup Repeat Specificity

DEFF Research Database (Denmark)

Vognsen, Tina Reinholdt; Möller, Ingvar Rúnar; Kristensen, Ole

2013-01-01

Ras GTPase Activating Protein SH3 Domain Binding Protein (G3BP) is a potential anti-cancer drug target implicated in several cellular functions. We have used protein crystallography to solve crystal structures of the human G3BP1 NTF2-like domain both alone and in complex with an FxFG Nup repeat...... peptide. Despite high structural similarity, the FxFG binding site is located between two alpha helices in the G3BP1 NTF2-like domain and not at the dimer interface as observed for nuclear transport factor 2. ITC studies showed specificity towards the FxFG motif but not FG and GLFG motifs. The unliganded...

BP's emissions trading system

International Nuclear Information System (INIS)

Victor, David G.; House, Joshua C.

2006-01-01

Between 1998 and 2001, BP reduced its emissions of greenhouse gases by more than 10%. BP's success in cutting emissions is often equated with its use of an apparently market-based emissions trading program. However no independent study has ever examined the rules and operation of BP's system and the incentives acting on managers to reduce emissions. We use interviews with key managers and with traders in several critical business units to explore the bound of BP's success with emissions trading. No money actually changed hands when permits were traded, and the main effect of the program was to create awareness of money-saving emission controls rather than strong price incentives. We show that the trading system did not operate like a 'textbook' cap and trade scheme. Rather, the BP system operated much like a 'safety valve' trading system, where managers let the market function until the cost of doing so surpassed what the company was willing to tolerate

Low p53 Binding Protein 1 (53BP1) Expression Is Associated With Increased Local Recurrence in Breast Cancer Patients Treated With Breast-Conserving Surgery and Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Neboori, Hanmanth J.R. [Department of Radiation Oncology, Cancer Institute of New Jersey and University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ (United States); Haffty, Bruce G., E-mail: hafftybg@umdnj.edu [Department of Radiation Oncology, The Cancer Institute of New Jersey and University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ (United States); Wu Hao [Department of Radiation Oncology, Cancer Institute of New Jersey and University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ (United States); Yang Qifeng [Department of Breast Surgery, Qilu Hospital, Shandong University, Ji' nan (China); Aly, Amal [Division of Medical Oncology, The Cancer Institute of New Jersey and University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ (United States); Goyal, Sharad; Schiff, Devora [Department of Radiation Oncology, Cancer Institute of New Jersey and University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ (United States); Moran, Meena S. [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT (United States); Golhar, Ryan [Department of Radiation Oncology, Cancer Institute of New Jersey and University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ (United States); Chen Chunxia; Moore, Dirk [Department of Biostatistics, The Cancer Institute of New Jersey and University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ (United States); and others

2012-08-01

Purpose: To investigate whether the expression of p53 binding protein 1 (53BP1) has prognostic significance in a cohort of early-stage breast cancer patients treated with breast-conserving surgery and radiotherapy (BCS+RT). Methods and Materials: A tissue microarray of early-stage breast cancer treated with BCS+RT from a cohort of 514 women was assayed for 53BP1, estrogen receptor, progesterone receptor, and HER2 expression by immunohistochemistry. Through log-rank tests and univariate and multivariate models, the staining profile of each tumor was correlated with clinical endpoints, including ipsilateral breast recurrence-free survival (IBRFS), distant metastasis-free survival (DMFS), cause-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS). Results: Of the 477 (93%) evaluable tumors, 63 (13%) were scored as low. Low expression of 53BP1 was associated with worse outcomes for all endpoints studied, including 10-year IBRFS (76.8% vs. 90.5%; P=.01), OS (66.4% vs. 81.7%; P=.02), CSS (66.0% vs. 87.4%; P<.01), DMFS (55.9% vs. 87.0%; P<.01), and RFS (45.2% vs. 80.6%; P<.01). Multivariate analysis incorporating various clinico-pathologic markers and 53BP1 expression found that 53BP1 expression was again an independent predictor of all endpoints (IBRFS: P=.0254; OS: P=.0094; CSS: P=.0033; DMFS: P=.0006; RFS: P=.0002). Low 53BP1 expression was also found to correlate with triple-negative (TN) phenotype (P<.01). Furthermore, in subset analysis of all TN breast cancer, negative 53BP1 expression trended for lower IBRFS (72.3% vs. 93.9%; P=.0361) and was significant for worse DMFS (48.2% vs. 86.8%; P=.0035) and RFS (37.8% vs. 83.7%; P=.0014). Conclusion: Our data indicate that low 53BP1 expression is an independent prognostic indicator for local relapse among other endpoints in early-stage breast cancer and TN breast cancer patients treated with BCS+RT. These results should be verified in larger cohorts of patients to validate their clinical

Low p53 Binding Protein 1 (53BP1) Expression Is Associated With Increased Local Recurrence in Breast Cancer Patients Treated With Breast-Conserving Surgery and Radiotherapy

International Nuclear Information System (INIS)

Neboori, Hanmanth J.R.; Haffty, Bruce G.; Wu Hao; Yang Qifeng; Aly, Amal; Goyal, Sharad; Schiff, Devora; Moran, Meena S.; Golhar, Ryan; Chen Chunxia; Moore, Dirk

2012-01-01

Purpose: To investigate whether the expression of p53 binding protein 1 (53BP1) has prognostic significance in a cohort of early-stage breast cancer patients treated with breast-conserving surgery and radiotherapy (BCS+RT). Methods and Materials: A tissue microarray of early-stage breast cancer treated with BCS+RT from a cohort of 514 women was assayed for 53BP1, estrogen receptor, progesterone receptor, and HER2 expression by immunohistochemistry. Through log–rank tests and univariate and multivariate models, the staining profile of each tumor was correlated with clinical endpoints, including ipsilateral breast recurrence–free survival (IBRFS), distant metastasis–free survival (DMFS), cause-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS). Results: Of the 477 (93%) evaluable tumors, 63 (13%) were scored as low. Low expression of 53BP1 was associated with worse outcomes for all endpoints studied, including 10-year IBRFS (76.8% vs. 90.5%; P=.01), OS (66.4% vs. 81.7%; P=.02), CSS (66.0% vs. 87.4%; P<.01), DMFS (55.9% vs. 87.0%; P<.01), and RFS (45.2% vs. 80.6%; P<.01). Multivariate analysis incorporating various clinico-pathologic markers and 53BP1 expression found that 53BP1 expression was again an independent predictor of all endpoints (IBRFS: P=.0254; OS: P=.0094; CSS: P=.0033; DMFS: P=.0006; RFS: P=.0002). Low 53BP1 expression was also found to correlate with triple-negative (TN) phenotype (P<.01). Furthermore, in subset analysis of all TN breast cancer, negative 53BP1 expression trended for lower IBRFS (72.3% vs. 93.9%; P=.0361) and was significant for worse DMFS (48.2% vs. 86.8%; P=.0035) and RFS (37.8% vs. 83.7%; P=.0014). Conclusion: Our data indicate that low 53BP1 expression is an independent prognostic indicator for local relapse among other endpoints in early-stage breast cancer and TN breast cancer patients treated with BCS+RT. These results should be verified in larger cohorts of patients to validate their

InterProScan Result: BP184018 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP184018 BP184018_2_ORF2 4FEA411FDBEADEDD PANTHER PTHR21347 CLEFT LIP AND PALATE ASSOCIATED TRANSME...MBRANE PROTEIN-RELATED 6.1e-73 T IPR008429 Cleft lip and palate transmembrane 1 ...

Distribución geográfica, prevalencia e intensidad de las infecciones de Gregarina ronderosi (Eugregarinorida: Gregarinidae en Dichroplus elongatus (Orthoptera: Acrididae

Directory of Open Access Journals (Sweden)

Christian Bardi

2016-01-01

Full Text Available regarina ronderosi es un parásito obligado del tracto digestivo del acrídido plaga Dichroplus elongatus y una de las únicas dos eugregarinas de acrídidos argentinos descriptas con su ciclo de vida completo. Dada la falta de conocimiento acerca de aspectos epizootiológicos fundamentales de las infecci- ones causadas por eugregarinas en acrídidos de Argentina, el objetivo de esta contribución es iniciar el registro de la distribución geográfica de G. ronderosi en la región Pampeana, su prevalencia natural y la intensidad de las infecciones en condiciones naturales. Para ello, se colectaron ejemplares de D. elongatus (2008 – 2012 en distintos puntos de la región Pampeana. Se obtuvieron y analizaron un total de 4084 ejemplares provenientes de cuarenta y dos localidades. La prevalen- cia promedio de G. ronderosi para el total de localidades con presencia (diecisiete localidades fue de 29,7 ± EE 6,6% (n = 1071. El total de individuos infectados (n = 396 fue categorizado respecto de la intensidad de las infecciones: tres (0,8% presentaron infecciones muy fuertes, ochenta (20% fuerte, doscientos diez (53% moderadas y ciento tres (26% infecciones leves. Se ha ampliado la distribución ge- ográfica conocida, se han registrado prevalencias elevadas que sugieren la ocur - rencia de epizootias y se han registrado por primera vez en condiciones naturales infecciones de G. ronderosi categorizadas como Fuertes y Muy Fuertes.

AcEST: BP918406 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000113_B06 468 Adiantum capillus-veneris mRNA. clone: YMU001_000113_B06. BP918406 - Show BP918406...is mRNA. clone: YMU001_000113_B06. Accession BP918406 Tissue type prothallium Developmental stage - Contig I...programs, Nucleic Acids Res. 25:3389-3402. Query= BP918406|Adiantum capillus-vene...ams, Nucleic Acids Res. 25:3389-3402. Query= BP918406|Adiantum capillus-veneris m

AcEST: BP918011 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000108_E11 519 Adiantum capillus-veneris mRNA. clone: YMU001_000108_E11. BP918011 - Show BP91801...is mRNA. clone: YMU001_000108_E11. Accession BP918011 Tissue type prothallium Developmental stage - Contig I...database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP918011|Adiant...se search programs, Nucleic Acids Res. 25:3389-3402. Query= BP918011|Adiantum cap

Vascular Type 1A Angiotensin II Receptors Control BP by Regulating Renal Blood Flow and Urinary Sodium Excretion.

Science.gov (United States)

Sparks, Matthew A; Stegbauer, Johannes; Chen, Daian; Gomez, Jose A; Griffiths, Robert C; Azad, Hooman A; Herrera, Marcela; Gurley, Susan B; Coffman, Thomas M

2015-12-01

Inappropriate activation of the type 1A angiotensin (AT1A) receptor contributes to the pathogenesis of hypertension and its associated complications. To define the role for actions of vascular AT1A receptors in BP regulation and hypertension pathogenesis, we generated mice with cell-specific deletion of AT1A receptors in smooth muscle cells (SMKO mice) using Loxp technology and Cre transgenes with robust expression in both conductance and resistance arteries. We found that elimination of AT1A receptors from vascular smooth muscle cells (VSMCs) caused a modest (approximately 7 mmHg) yet significant reduction in baseline BP and exaggerated sodium sensitivity in mice. Additionally, the severity of angiotensin II (Ang II)-dependent hypertension was dramatically attenuated in SMKO mice, and this protection against hypertension was associated with enhanced urinary excretion of sodium. Despite the lower BP, acute vasoconstrictor responses to Ang II in the systemic vasculature were largely preserved (approximately 80% of control levels) in SMKO mice because of exaggerated activity of the sympathetic nervous system rather than residual actions of AT1B receptors. In contrast, Ang II-dependent responses in the renal circulation were almost completely eliminated in SMKO mice (approximately 5%-10% of control levels). These findings suggest that direct actions of AT1A receptors in VSMCs are essential for regulation of renal blood flow by Ang II and highlight the capacity of Ang II-dependent vascular responses in the kidney to effect natriuresis and BP control. Copyright © 2015 by the American Society of Nephrology.

Instrument evaluation no. 16. Nuclear enterprises portable doserate meter type PDR4 and external probes types BP1/1, BP8 and GP9

International Nuclear Information System (INIS)

Burgess, P.H.; Iles, W.J.

1979-08-01

The various radiations encountered in radiological protection cover a wide range of energies and radiation measurements have to be carried out under an equally broad spectrum of environmental conditions. This report is one of a series intended to give information on the performance characteristics of radiological protection instruments, to assist in the selection of appropriate instruments for a given purpose, to interpret the results obtained with such instruments, and, in particular, to know the likely sources and magnitude of errors that might be associated with measurements in the field. The radiation, electrical and environmental characteristics of radiation protection instruments are considered together with those aspects of the construction which make an instrument convenient for routine use. To provide consistent criteria for instrument performance, the range of tests performed on any particular class of instrument, the test methods and the criteria of acceptable performance are based broadly on the appropriate Recommendations of the International Electrotechnical Commission. The radiations in the tests are, in general, selected from the range of reference radiations for instrument calibration being drawn up by the International Standards Organisation. Normally, each report deals with the capabilities and limitations of one model of instrument and no direct comparison with other instruments intended for similar purposes is made, since the significance of particular performance characteristics largely depends on the radiations and environmental conditions in which the instrument is to be used. The results quoted here have all been obtained from tests on instruments in routine production, with the appropriate measurements being made by the NRPB. This report presents the evaluation of Nuclear Enterprises Portable Doserate Meter Type PDR4 and External Probes Types BP1/1, BP8 and GP9

Polymer-Based Black Phosphorus (bP) Hybrid Materials by in Situ Radical Polymerization: An Effective Tool To Exfoliate bP and Stabilize bP Nanoflakes

Science.gov (United States)

2018-01-01

Black phosphorus (bP) has been recently investigated for next generation nanoelectronic multifunctional devices. However, the intrinsic instability of exfoliated bP (the bP nanoflakes) toward both moisture and air has so far overshadowed its practical implementation. In order to contribute to fill this gap, we report here the preparation of new hybrid polymer-based materials where bP nanoflakes (bPn) exhibit a significantly improved stability. The new materials have been prepared by different synthetic paths including: (i) the mixing of conventionally liquid-phase exfoliated bP (in dimethyl sulfoxide, DMSO) with poly(methyl methacrylate) (PMMA) solution; (ii) the direct exfoliation of bP in a polymeric solution; (iii) the in situ radical polymerization after exfoliating bP in the liquid monomer (methyl methacrylate, MMA). This last methodology concerns the preparation of stable suspensions of bPn–MMA by sonication-assisted liquid-phase exfoliation (LPE) of bP in the presence of MMA followed by radical polymerization. The hybrids characteristics have been compared in order to evaluate the bP dispersion and the effectiveness of the bPn interfacial interactions with polymer chains aimed at their long-term environmental stabilization. The passivation of the bPn is particularly effective when the hybrid material is prepared by in situ polymerization. By using this synthetic methodology, the nanoflakes, even if with a gradient of dispersion (size of aggregates), preserve their chemical structure from oxidation (as proved by both Raman and 31P-solid state NMR studies) and are particularly stable to air and UV light exposure. The feasibility of this approach, capable of efficiently exfoliating bP while protecting the bPn, has been then verified by using different vinyl monomers (styrene and N-vinylpyrrolidone), thus obtaining hybrids where the nanoflakes are embedded in polymer matrices with a variety of intriguing thermal, mechanical, and solubility characteristics.

AcEST: BP911801 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000009_C12 487 Adiantum capillus-veneris mRNA. clone: YMU001_000009_C12. BP911801 - Show BP911801...is mRNA. clone: YMU001_000009_C12. Accession BP911801 Tissue type prothallium Developmental stage - Contig I...generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP911801.... 25:3389-3402. Query= BP911801|Adiantum capillus-veneris mRNA, clone: YMU001_000

Photoautotrophic production of polyhydroxyalkanoates in a synthetic mixed culture of Synechococcus elongatus cscB and Pseudomonas putida cscAB.

Science.gov (United States)

Löwe, Hannes; Hobmeier, Karina; Moos, Manuel; Kremling, Andreas; Pflüger-Grau, Katharina

2017-01-01

One of the major challenges for the present and future generations is to find suitable substitutes for the fossil resources we rely on today. Cyanobacterial carbohydrates have been discussed as an emerging renewable feedstock in industrial biotechnology for the production of fuels and chemicals, showing promising production rates when compared to crop-based feedstock. However, intrinsic capacities of cyanobacteria to produce biotechnological compounds are limited and yields are low. Here, we present an approach to circumvent these problems by employing a synthetic bacterial co-culture for the carbon-neutral production of polyhydroxyalkanoates (PHAs) from CO 2 . The co-culture consists of two bio - modules : Bio - module I , in which the cyanobacterial strain Synechococcus elongatus cscB fixes CO 2 , converts it to sucrose, and exports it into the culture supernatant; and bio - module II , where this sugar serves as C-source for Pseudomonas putida cscAB and is converted to PHAs that are accumulated in the cytoplasm. By applying a nitrogen-limited process, we achieved a maximal PHA production rate of 23.8 mg/(L day) and a maximal titer of 156 mg/L. We will discuss the present shortcomings of the process and show the potential for future improvement. These results demonstrate the feasibility of mixed cultures of S. elongatus cscB and P. putida cscAB for PHA production, making room for the cornucopia of possible products that are described for P. putida . The construction of more efficient sucrose-utilizing P. putida phenotypes and the optimization of process conditions will increase yields and productivities and eventually close the gap in the contemporary process. In the long term, the co-culture may serve as a platform process, in which P. putida is used as a chassis for the implementation of synthetic metabolic pathways for biotechnological production of value-added products.

Flow cytometric evaluation of the effects of 3-bromopyruvate (3BP) and dichloracetate (DCA) on THP-1 cells: a multiparameter analysis

NARCIS (Netherlands)

Verhoeven, H.A.; Griensven, van L.J.L.D.

2012-01-01

Two human leukemia cells K562 and THP-1, the breast cancer lines MCF-7 and ZR-75-1, and the melanoma line MDA-MB-435S were compared by flowcytometry for their behaviour at increasing levels of 3BP. K562 and THP-1 responded to 3BP by membrane depolarization and increased ROS; MCF-7 and ZR-75-1 showed

AcEST: BP920145 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000133_E11 274 Adiantum capillus-veneris mRNA. clone: YMU001_000133_E11. BP920145 - Show BP92014...is mRNA. clone: YMU001_000133_E11. Accession BP920145 Tissue type prothallium Developmental stage - Contig I..., Nucleic Acids Res. 25:3389-3402. Query= BP920145|Adiantum capillus-veneris mRNA, clone: YMU001_000133_E11.... database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP920145|Adian

AcEST: BP920142 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000133_E05 486 Adiantum capillus-veneris mRNA. clone: YMU001_000133_E05. BP920142 - Show BP92014...is mRNA. clone: YMU001_000133_E05. Accession BP920142 Tissue type prothallium Developmental stage - Contig I...rotein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP920142|Adiantum capillus-veneris ...rograms, Nucleic Acids Res. 25:3389-3402. Query= BP920142|Adiantum capillus-veneris mRNA, clone: YMU001_0001

AcEST: BP919406 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000124_G04 562 Adiantum capillus-veneris mRNA. clone: YMU001_000124_G04. BP919406 - Show BP919406...is mRNA. clone: YMU001_000124_G04. Accession BP919406 Tissue type prothallium Developmental stage - Contig I...ion of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP919406|Adiantum capillus-...ucleic Acids Res. 25:3389-3402. Query= BP919406|Adiantum capillus-veneris mRNA, c

AcEST: BP921000 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000144_D05 407 Adiantum capillus-veneris mRNA. clone: YMU001_000144_D05. BP921000 - Show BP921000...is mRNA. clone: YMU001_000144_D05. Accession BP921000 Tissue type prothallium Developmental stage - Contig I...eneration of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP921000|Adiantum cap...ein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP921000|Adiantum capillus-veneris mRN

AcEST: BP920995 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000144_C12 350 Adiantum capillus-veneris mRNA. clone: YMU001_000144_C12. BP920995 - Show BP92099...is mRNA. clone: YMU001_000144_C12. Accession BP920995 Tissue type prothallium Developmental stage - Contig I...-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP92099...ew generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP92099

AcEST: BP918015 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000108_F03 437 Adiantum capillus-veneris mRNA. clone: YMU001_000108_F03. BP918015 - Show BP91801...is mRNA. clone: YMU001_000108_F03. Accession BP918015 Tissue type prothallium Developmental stage - Contig I.... 25:3389-3402. Query= BP918015|Adiantum capillus-veneris mRNA, clone: YMU001_000108_F03. (437 letters) Data...eration of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP91801

AcEST: BP918018 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000108_F06 436 Adiantum capillus-veneris mRNA. clone: YMU001_000108_F06. BP918018 - Show BP91801...is mRNA. clone: YMU001_000108_F06. Accession BP918018 Tissue type prothallium Developmental stage - Contig I...cids Res. 25:3389-3402. Query= BP918018|Adiantum capillus-veneris mRNA, clone: YM...and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP91801

AcEST: BP912801 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000023_A07 527 Adiantum capillus-veneris mRNA. clone: YMU001_000023_A07. BP912801 - Show BP912801...is mRNA. clone: YMU001_000023_A07. Accession BP912801 Tissue type prothallium Developmental stage - Contig I...w generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP912801...es. 25:3389-3402. Query= BP912801|Adiantum capillus-veneris mRNA, clone: YMU001_0

Recruitment kinetics of DNA repair proteins Mdc1 and Rad52 but not 53BP1 depend on damage complexity.

Directory of Open Access Journals (Sweden)

Volker Hable

Full Text Available The recruitment kinetics of double-strand break (DSB signaling and repair proteins Mdc1, 53BP1 and Rad52 into radiation-induced foci was studied by live-cell fluorescence microscopy after ion microirradiation. To investigate the influence of damage density and complexity on recruitment kinetics, which cannot be done by UV laser irradiation used in former studies, we utilized 43 MeV carbon ions with high linear energy transfer per ion (LET = 370 keV/µm to create a large fraction of clustered DSBs, thus forming complex DNA damage, and 20 MeV protons with low LET (LET = 2.6 keV/µm to create mainly isolated DSBs. Kinetics for all three proteins was characterized by a time lag period T(0 after irradiation, during which no foci are formed. Subsequently, the proteins accumulate into foci with characteristic mean recruitment times τ(1. Mdc1 accumulates faster (T(0 = 17 ± 2 s, τ(1 = 98 ± 11 s than 53BP1 (T(0 = 77 ± 7 s, τ(1 = 310 ± 60 s after high LET irradiation. However, recruitment of Mdc1 slows down (T(0 = 73 ± 16 s, τ(1 = 1050 ± 270 s after low LET irradiation. The recruitment kinetics of Rad52 is slower than that of Mdc1, but exhibits the same dependence on LET. In contrast, the mean recruitment time τ(1 of 53BP1 remains almost constant when varying LET. Comparison to literature data on Mdc1 recruitment after UV laser irradiation shows that this rather resembles recruitment after high than low LET ionizing radiation. So this work shows that damage quality has a large influence on repair processes and has to be considered when comparing different studies.

AcEST: BP914068 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000039_E04 420 Adiantum capillus-veneris mRNA. clone: YMU001_000039_E04. BP914068 - Show BP91406...is mRNA. clone: YMU001_000039_E04. Accession BP914068 Tissue type prothallium Developmental stage - Contig I...PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP91406...se search programs, Nucleic Acids Res. 25:3389-3402. Query= BP914068|Adiantum capillus-veneris mRNA, clone:

AcEST: BP915406 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000071_B11 433 Adiantum capillus-veneris mRNA. clone: YMU001_000071_B11. BP915406 - Show BP915406...is mRNA. clone: YMU001_000071_B11. Accession BP915406 Tissue type prothallium Developmental stage - Contig I...Acids Res. 25:3389-3402. Query= BP915406|Adiantum capillus-veneris mRNA, clone: Y...leic Acids Res. 25:3389-3402. Query= BP915406|Adiantum capillus-veneris mRNA, clone: YMU001_000071_B11. (433

AcEST: BP912099 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000015_B05 315 Adiantum capillus-veneris mRNA. clone: YMU001_000015_B05. BP912099 - Show BP912099...is mRNA. clone: YMU001_000015_B05. Accession BP912099 Tissue type prothallium Developmental stage - Contig I...BLAST and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP912099...of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP912099|Adiantum capillus-vene

AcEST: BP918801 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000117_F03 542 Adiantum capillus-veneris mRNA. clone: YMU001_000117_F03. BP918801 - Show BP918801...is mRNA. clone: YMU001_000117_F03. Accession BP918801 Tissue type prothallium Developmental stage - Contig I...earch programs, Nucleic Acids Res. 25:3389-3402. Query= BP918801|Adiantum capillus-veneris mRNA, clone: YMU0...generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP918801|Adiantum ca

AcEST: BP917801 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000105_F04 280 Adiantum capillus-veneris mRNA. clone: YMU001_000105_F04. BP917801 - Show BP917801...is mRNA. clone: YMU001_000105_F04. Accession BP917801 Tissue type prothallium Developmental stage - Contig I...n of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP917801|Adiantum capillus-ve... Nucleic Acids Res. 25:3389-3402. Query= BP917801|Adiantum capillus-veneris mRNA, clone: YMU001_000105_F04.

AcEST: BP918017 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000108_F05 267 Adiantum capillus-veneris mRNA. clone: YMU001_000108_F05. BP918017 - Show BP91801...is mRNA. clone: YMU001_000108_F05. Accession BP918017 Tissue type prothallium Developmental stage - Contig I...otein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP918017|Adiantum capillus-veneris m...cleic Acids Res. 25:3389-3402. Query= BP918017|Adiantum capillus-veneris mRNA, clone: YMU001_000108_F05. (26

AcEST: BP915801 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000077_B02 555 Adiantum capillus-veneris mRNA. clone: YMU001_000077_B02. BP915801 - Show BP915801...is mRNA. clone: YMU001_000077_B02. Accession BP915801 Tissue type prothallium Developmental stage - Contig I... Nucleic Acids Res. 25:3389-3402. Query= BP915801|Adiantum capillus-veneris mRNA, clone: YMU001_000077_B02. ...ST: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP915801|A

Dpb11/TopBP1 plays distinct roles in DNA replication, checkpoint response and homologous recombination

DEFF Research Database (Denmark)

Germann, Susanne Manuela; Østergaard, Vibe Hallundbæk; Haas, Caroline

2011-01-01

DPB11/TopBP1 is an essential evolutionarily conserved gene involved in initiation of DNA replication and checkpoint signaling. Here, we show that Saccharomyces cerevisiae Dpb11 forms nuclear foci that localize to sites of DNA damage in G1, S and G2 phase, a recruitment that is conserved for its...... and Tel1, and of the checkpoint mediator Rad9. In a site-directed mutagenesis screen, we identify a separation-of-function mutant, dpb11-PF, that is sensitive to DSB-inducing agents yet remains proficient for DNA replication and the S-phase checkpoint at the permissive temperature. The dpb11-PF mutant...... homologue TopBP1 in Gallus gallus. Damage-induced Dpb11 foci are distinct from Sld3 replication initiation foci. Further, Dpb11 foci are dependent on the checkpoint proteins Mec3 (9-1-1 complex) and Rad24, and require the C-terminal domain of Dpb11. Dpb11 foci are independent of the checkpoint kinases Mec1...

An 8bp indel in exon 1 of Ghrelin gene associated with chicken growth.

Science.gov (United States)

Fang, Meixia; Nie, Qinghua; Luo, Chenglong; Zhang, Dexiang; Zhang, Xiquan

2007-04-01

Ghrelin, acts as the endogenous ligand for growth hormone secretagogues receptor (GHS-R), is a novel growth hormone (GH) releasing peptide with reported effects on food intake in chickens. In this study, an 8 bp indel polymorphism in exon 1 of the chicken Ghrelin (cGHRL) gene was genotyped in a F(2) designed full-sib population to analyze its associations with chicken growth and carcass traits. Later, mRNA level in the proventriculus was determined by real-time PCR to reveal the expression feature of cGHRL gene. Result showed that this 8 bp indel was significantly associated with body weight at the age of 28 days (BW28) and 56 days (BW56), eviscerated weight (EW) and leg muscle weight (LMW) (PGhrelin on chicken growth were indicated by this study.

Proximate composition, mineral content and fatty acid profile of two marine fishes from Cameroonian coast: Pseudotolithus typus (Bleeker, 1863 and Pseudotolithus elongatus (Bowdich, 1825

Directory of Open Access Journals (Sweden)

J.M. Njinkoue

2016-10-01

Full Text Available Background: Knowledge of chemical composition of fish from Cameroon is poor. The genera Pseudotolithus are nutritionally and economically important in Cameroon. Thus the knowledge on their chemical composition could help in functional food elaboration. Purpose: In this study, Proximate composition, fatty acid profiles and mineral composition were determined in two fish species, Pseudotolithus typus and Pseudotolithus elongatus from Cameroonian coasts. Basic procedure: AOAC standard method was used. Fatty acids were identified by GC/MS as N-acylpyrolidides. Mineral compositions were determined by atomic absorption spectrophotometry for Ca, Na, K, Mg, Fe, Zn, Cu, Mn, and by UV spectrophotometry for phosphorus (P. Main finding: Results indicated that chemical composition was not similar in the two fish species. Results also showed that water is the main constituent in the edible parts and in the bones with 76.17% to 78.24% and 51.21% to 55.28% respectively. Pseudotolithus typus and Pseudotolithus elongatus were good sources of proteins with 16.17% and 13.4% respectively. All the fish analyzed for fat were lean with fat contents less than 0.5%. These species of fish were poor in ω6PUFA and were rich in ω3PUFA with about one third of total fatty acids. The main ω3 fatty acids were eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. The most abundant main elements were the potassium in the edible parts (1.39% and calcium in the bones (18.26%. The most abundant trace elements were Zn and Fe in the edible parts and in the bones. Principal conclusion: The Na/K ratio values and ω3 fatty acids contents suggest that consumption of these two fish species could be recommended to prevent cardiovascular diseases. Keywords: Proximal composition, Mineral content, Fatty acid profiles, Pseudotolithus typus, Pseudotolithus elongates

A biallelic 36-bp insertion in PIBF1 is associated with Joubert syndrome.

Science.gov (United States)

Hebbar, Malavika; Kanthi, Anil; Shukla, Anju; Bielas, Stephanie; Girisha, Katta M

2018-04-25

Biallelic pathogenic variants in PIBF1 have been identified as one of the genetic etiologies of Joubert syndrome. We report a two-year-old girl with global developmental delay, facial dysmorphism, hypotonia, enlarged cystic kidneys, molar tooth sign, and thinning of corpus callosum. A novel homozygous 36-bp insertion in PIBF1 (c.1181_1182ins36) was identified by exome sequencing as the likely cause of her condition. This is the second publication demonstrating the cause and effect relationship between PIBF1 and Joubert syndrome.

AcEST: BP920147 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000133_F01 365 Adiantum capillus-veneris mRNA. clone: YMU001_000133_F01. BP920147 - Show BP92014...is mRNA. clone: YMU001_000133_F01. Accession BP920147 Tissue type prothallium Developmental stage - Contig I...ch programs, Nucleic Acids Res. 25:3389-3402. Query= BP920147|Adiantum capillus-veneris mRNA, clone: YMU001_...97), Gapped BLAST and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP9201

AcEST: BP920144 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000133_E09 265 Adiantum capillus-veneris mRNA. clone: YMU001_000133_E09. BP920144 - Show BP92014...is mRNA. clone: YMU001_000133_E09. Accession BP920144 Tissue type prothallium Developmental stage - Contig I...rch programs, Nucleic Acids Res. 25:3389-3402. Query= BP920144|Adiantum capillus-veneris mRNA, clone: YMU001...LAST and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP92014

AcEST: BP920141 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000133_E04 528 Adiantum capillus-veneris mRNA. clone: YMU001_000133_E04. BP920141 - Show BP92014...is mRNA. clone: YMU001_000133_E04. Accession BP920141 Tissue type prothallium Developmental stage - Contig I...cids Res. 25:3389-3402. Query= BP920141|Adiantum capillus-veneris mRNA, clone: YMU001_000133_E04. (528 lette...cleic Acids Res. 25:3389-3402. Query= BP920141|Adiantum capillus-veneris mRNA, clone: YMU001_000133_E04. (52

AcEST: BP913406 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000029_H06 570 Adiantum capillus-veneris mRNA. clone: YMU001_000029_H06. BP913406 - Show BP913406...is mRNA. clone: YMU001_000029_H06. Accession BP913406 Tissue type prothallium Developmental stage - Contig I...arch programs, Nucleic Acids Res. 25:3389-3402. Query= BP913406|Adiantum capillus-veneris mRNA, clone: YMU00...eration of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP913406|Adiantum capil...LDVTRGLVNGARGVVVAFES--GKHG---------------LPH 406 Query: 387 VRFACNRAEIVIGPDRQTVESGGMQVARRIQVPLILAWALSVHKCQGM

Phosphatase control of 4E-BP1 phosphorylation state is central for glycolytic regulation of retinal protein synthesis.

Science.gov (United States)

Gardner, Thomas W; Abcouwer, Steven F; Losiewicz, Mandy K; Fort, Patrice E

2015-09-15

Control of protein synthesis in insulin-responsive tissues has been well characterized, but relatively little is known about how this process is regulated in nervous tissues. The retina exhibits a relatively high protein synthesis rate, coinciding with high basal Akt and metabolic activities, with the majority of retinal ATP being derived from aerobic glycolysis. We examined the dependency of retinal protein synthesis on the Akt-mTOR signaling and glycolysis using ex vivo rat retinas. Akt inhibitors significantly reduced retinal protein synthesis but did not affect glycolytic lactate production. Surprisingly, the glycolytic inhibitor 2-deoxyglucose (2-DG) markedly inhibited Akt1 and Akt3 activities, as well as protein synthesis. The effects of 2-DG, and 2-fluorodeoxyglucose (2-FDG) on retinal protein synthesis correlated with inhibition of lactate production and diminished ATP content, with all these effects reversed by provision of d-mannose. 2-DG treatment was not associated with increased AMPK, eEF2, or eIF2α phosphorylation; instead, it caused rapid dephosphorylation of 4E-BP1. 2-DG reduced total mTOR activity by 25%, but surprisingly, it did not reduce mTORC1 activity, as indicated by unaltered raptor-associated mTOR autophosphorylation and ribosomal protein S6 phosphorylation. Dephosphorylation of 4E-BP1 was largely prevented by inhibition of PP1/PP2A phosphatases with okadaic acid and calyculin A, and inhibition of PPM1 phosphatases with cadmium. Thus, inhibition of retinal glycolysis diminished Akt and protein synthesis coinciding with accelerated dephosphorylation of 4E-BP1 independently of mTORC1. These results demonstrate a novel mechanism regulating protein synthesis in the retina involving an mTORC1-independent and phosphatase-dependent regulation of 4E-BP1. Copyright © 2015 the American Physiological Society.

Profile of NF-κBp(65/NFκBp50) among prostate specific antigen sera levels in prostatic pathologies.

Science.gov (United States)

Bouraoui, Y; Ben Jemaa, A; Rodriguez, G; Ben Rais, N; Fraile, B; Paniagua, R; Sellemi, S; Royuela, M; Oueslati, R

2012-10-01

The aim of this work was to characterise the immunoexpression of NF-κB (p50/p65) in human prostatic pathologies and to study its profiles of activation among sera prostate specific antigen antigen (PSA) according the three groups: 0-4ng/mL, 4-20ng/mL and >20ng/mL. Twenty-four men with benign prostate hyperplasia (BPH); 19 men with prostate cancer (PC) and five men with normal prostates (NP). Immunohistochemical and western blot analysis was performed. Serum levels of PSA were assayed by immulite autoanalyser. In BPH and PC samples, immunoexpressions were observed for NF-κBp65 and NF-κBp50; while in NP samples, only were detected NF-κBp50. PC samples showed immunoreactions to NF-κBp65 and NF-κBp50 more intense (respectively 24.18±0.67 and 28.23±2.01) than that observed in BPH samples (respectively18.46±2.04 and 18.66±1.59) with special localisation in the nucleus. Different profiles of NF-κBp65 immunoexpressions were observed and BPH patients with sera PSA levels between 0-4ng/mL presented a significant weak percentage compared to BPH patients with sera PSA levels between 4-20ng/mL and >20ng/mL. No immunoreactions to NF-κBp65 were observed in PC patients with sera PSA levels between 4-20ng/mL. The sensibility of both NF-κB and PSA to inflammation allowed confirming the relationship between these two molecules and its involvement in prostatic diseases progression (inflammatory and neoplasic). Copyright © 2011 Elsevier Masson SAS. All rights reserved.

53BP1 and USP28 mediate p53-dependent cell cycle arrest in response to centrosome loss and prolonged mitosis.

Science.gov (United States)

Fong, Chii Shyang; Mazo, Gregory; Das, Tuhin; Goodman, Joshua; Kim, Minhee; O'Rourke, Brian P; Izquierdo, Denisse; Tsou, Meng-Fu Bryan

2016-07-02

Mitosis occurs efficiently, but when it is disturbed or delayed, p53-dependent cell death or senescence is often triggered after mitotic exit. To characterize this process, we conducted CRISPR-mediated loss-of-function screens using a cell-based assay in which mitosis is consistently disturbed by centrosome loss. We identified 53BP1 and USP28 as essential components acting upstream of p53, evoking p21-dependent cell cycle arrest in response not only to centrosome loss, but also to other distinct defects causing prolonged mitosis. Intriguingly, 53BP1 mediates p53 activation independently of its DNA repair activity, but requiring its interacting protein USP28 that can directly deubiquitinate p53 in vitro and ectopically stabilize p53 in vivo. Moreover, 53BP1 can transduce prolonged mitosis to cell cycle arrest independently of the spindle assembly checkpoint (SAC), suggesting that while SAC protects mitotic accuracy by slowing down mitosis, 53BP1 and USP28 function in parallel to select against disturbed or delayed mitosis, promoting mitotic efficiency.

Low-dose ionizing irradiation triggers a 53BP1 response to DNA double strand breaks in mouse spermatogonial stem cells.

Science.gov (United States)

Le, Wei; Qi, Lixin; Li, Jiaxuan; Wu, DengIong; Xu, Jun; Zhang, Jinfu

2016-01-01

The present study aims to examine the effect of low-dose ionizing irradiation on DNA double strand breaks (DSB) in mouse spermatogonial stem cells (SSCs) and reveal the underlying pathways for the DNA repair for DSB in SSCs. Eighteen one-month-old mice were divided into 6 groups and sacrificed separately at 45 minutes, 2 hours, 24 hours, 48 hours, and 72 hours after 0.1Gy X-ray irradiation (mice without receiving ionizing irradiation served as control). After perfusion fixation, testes were removed, sectioned, and followed by staining of γH2AX, 53BP1, Caspase 3, and promyelocytic leukemia zinc-finger (PLZF) for analysis among the different groups. The staining was observed by immunofluorescence visualized by confocal laser scanning. After low-dose irradiation, only 53BP1, but not Caspase3 or γH2AX was upregulated in PLZF positive SSCs within 45 minutes. The expression level of 53BP1 gradually decreased 24 hours after irradiation. Moreover, low-dose irradiation had no effect on the cell number and apoptotic status of SSCs. However other spermatogenic cells highly expressed γH2AX shortly after irradiation which was dramatically reduced following the events of DNA repair. It appears that low-dose ionizing irradiation may cause the DNA DSB of mouse spermatogenic cells. 53BP1, but not γH2AX, is involved in the DNA repair for DSB in SSCs. Our data indicates that 53BP1 plays an important role in the pathophysiological repair of DNA DSB in SSCs. This may open a new avenue to understanding the mechanisms of DNA repair of SSCs and male infertility.

InterProScan Result: BP124291 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP124291 BP124291_5_ORF1 92B626ADD33C8436 PFAM PF00067 p450 1.8e-09 T IPR001128 Cytochrome P450 Molecular... Function: monooxygenase activity (GO:0004497)|Molecular Function: iron ion binding (GO:0005506)|Molecular... Function: electron carrier activity (GO:0009055)|Molecular Function: heme binding (GO:0020037) ...

InterProScan Result: BP123442 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP123442 BP123442_1_ORF1 331440C6CA592A17 PRINTS PR00385 P450 6.3e-05 T IPR001128 Cytochrome P450 Molecular... Function: monooxygenase activity (GO:0004497)|Molecular Function: iron ion binding (GO:0005506)|Molecular... Function: electron carrier activity (GO:0009055)|Molecular Function: heme binding (GO:0020037) ...

Apo-states of calmodulin and CaBP1 control CaV1 voltage-gated calcium channel function through direct competition for the IQ domain

Science.gov (United States)

Findeisen, Felix; Rumpf, Christine; Minor, Daniel L.

2013-01-01

In neurons, binding of calmodulin (CaM) or calcium-binding protein 1 (CaBP1) to the CaV1 (L-type) voltage-gated calcium channel IQ domain endows the channel with diametrically opposed properties. CaM causes calcium-dependent inactivation (CDI) and limits calcium entry, whereas CaBP1 blocks CDI and allows sustained calcium influx. Here, we combine isothermal titration calorimetry (ITC) with cell-based functional measurements and mathematical modeling to show that these calcium sensors behave in a competitive manner that is explained quantitatively by their apo-state binding affinities for the IQ domain. This competition can be completely blocked by covalent tethering of CaM to the channel. Further, we show that Ca2+/CaM has a sub-picomolar affinity for the IQ domain that is achieved without drastic alteration of calcium binding properties. The observation that the apo-forms of CaM and CaBP1 compete with each other demonstrates a simple mechanism for direct modulation of CaV1 function and suggests a means by which excitable cells may dynamically tune CaV activity. PMID:23811053

Apo states of calmodulin and CaBP1 control CaV1 voltage-gated calcium channel function through direct competition for the IQ domain.

Science.gov (United States)

Findeisen, Felix; Rumpf, Christine H; Minor, Daniel L

2013-09-09

In neurons, binding of calmodulin (CaM) or calcium-binding protein 1 (CaBP1) to the CaV1 (L-type) voltage-gated calcium channel IQ domain endows the channel with diametrically opposed properties. CaM causes calcium-dependent inactivation and limits calcium entry, whereas CaBP1 blocks calcium-dependent inactivation (CDI) and allows sustained calcium influx. Here, we combine isothermal titration calorimetry with cell-based functional measurements and mathematical modeling to show that these calcium sensors behave in a competitive manner that is explained quantitatively by their apo-state binding affinities for the IQ domain. This competition can be completely blocked by covalent tethering of CaM to the channel. Further, we show that Ca(2+)/CaM has a sub-picomolar affinity for the IQ domain that is achieved without drastic alteration of calcium-binding properties. The observation that the apo forms of CaM and CaBP1 compete with each other demonstrates a simple mechanism for direct modulation of CaV1 function and suggests a means by which excitable cells may dynamically tune CaV activity. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

A perillyl alcohol-conjugated analog of 3-bromopyruvate without cellular uptake dependency on monocarboxylate transporter 1 and with activity in 3-BP-resistant tumor cells.

Science.gov (United States)

Chen, Thomas C; Yu, Jiali; Nouri Nigjeh, Eslam; Wang, Weijun; Myint, Phyo Thazin; Zandi, Ebrahim; Hofman, Florence M; Schönthal, Axel H

2017-08-01

The anticancer agent 3-bromopyruvate (3-BP) is viewed as a glycolytic inhibitor that preferentially kills glycolytic cancer cells through energy depletion. However, its cytotoxic activity is dependent on cellular drug import through transmembrane monocarboxylate transporter 1 (MCT-1), which restricts its anticancer potential to MCT-1-positive tumor cells. We created and characterized an MCT-1-independent analog of 3-BP, called NEO218. NEO218 was synthesized by covalently conjugating 3-BP to perillyl alcohol (POH), a natural monoterpene. The responses of various tumor cell lines to treatment with either compound were characterized in the presence or absence of supplemental pyruvate or antioxidants N-acetyl-cysteine (NAC) and glutathione (GSH). Drug effects on glyceraldehyde 3-phosphate dehydrogenase (GAPDH) enzyme activity were investigated by mass spectrometric analysis. The development of 3-BP resistance was investigated in MCT-1-positive HCT116 colon carcinoma cells in vitro. Our results show that NEO218: (i) pyruvylated GAPDH on all 4 of its cysteine residues and shut down enzymatic activity; (ii) severely lowered cellular ATP content below life-sustaining levels, and (iii) triggered rapid necrosis. Intriguingly, supplemental antioxidants effectively prevented cytotoxic activity of NEO218 as well as 3-BP, but supplemental pyruvate powerfully protected cells only from 3-BP, not from NEO218. Unlike 3-BP, NEO218 exerted its potent cytotoxic activity irrespective of cellular MCT-1 status. Treatment of HCT116 cells with 3-BP resulted in prompt development of resistance, based on the emergence of MCT-1-negative cells. This was not the case with NEO218, and highly 3-BP-resistant cells remained exquisitely sensitive to NEO218. Thus, our study identifies a mechanism by which tumor cells develop rapid resistance to 3-BP, and presents NEO218 as a superior agent not subject to this cellular defense. Furthermore, our results offer alternative interpretations of previously

Hepatitis C virus core protein targets 4E-BP1 expression and phosphorylation and potentiates Myc-induced liver carcinogenesis in transgenic mice.

Science.gov (United States)

Abdallah, Cosette; Lejamtel, Charlène; Benzoubir, Nassima; Battaglia, Serena; Sidahmed-Adrar, Nazha; Desterke, Christophe; Lemasson, Matthieu; Rosenberg, Arielle R; Samuel, Didier; Bréchot, Christian; Pflieger, Delphine; Le Naour, François; Bourgeade, Marie-Françoise

2017-08-22

Hepatitis C virus (HCV) is a leading cause of liver diseases including the development of hepatocellular carcinoma (HCC). Particularly, core protein has been involved in HCV-related liver pathologies. However, the impact of HCV core on signaling pathways supporting the genesis of HCC remains largely elusive. To decipher the host cell signaling pathways involved in the oncogenic potential of HCV core, a global quantitative phosphoproteomic approach was carried out. This study shed light on novel differentially phosphorylated proteins, in particular several components involved in translation. Among the eukaryotic initiation factors that govern the translational machinery, 4E-BP1 represents a master regulator of protein synthesis that is associated with the development and progression of cancers due to its ability to increase protein expression of oncogenic pathways. Enhanced levels of 4E-BP1 in non-modified and phosphorylated forms were validated in human hepatoma cells and in mouse primary hepatocytes expressing HCV core, in the livers of HCV core transgenic mice as well as in HCV-infected human primary hepatocytes. The contribution of HCV core in carcinogenesis and the status of 4E-BP1 expression and phosphorylation were studied in HCV core/Myc double transgenic mice. HCV core increased the levels of 4E-BP1 expression and phosphorylation and significantly accelerated the onset of Myc-induced tumorigenesis in these double transgenic mice. These results reveal a novel function of HCV core in liver carcinogenesis potentiation. They position 4E-BP1 as a tumor-specific target of HCV core and support the involvement of the 4E-BP1/eIF4E axis in hepatocarcinogenesis.

The 160 bp insertion in the promoter of Rht-B1i plays a vital role in increasing wheat height

Directory of Open Access Journals (Sweden)

Xueyuan eLou

2016-03-01

Full Text Available The extensive use of two alleles (Rht-B1b and Rht-D1b at the Rht-1 locus in wheat allowed dramatic increases in yields, triggering the so-called Green Revolution. Here, we found that a new natural allelic variation (Rht-B1i containing a single missense SNP (A614G in the coding region significantly increased plant height against the genetic background of both Rht-D1a (11.68% and Rht-D1b (7.89%. To elucidate the molecular mechanism of Rht-B1i, we investigated the promoter region. Sequence analysis showed that the Rht-B1i promoter could be divided into two classes depending on the presence or absence of a specific 160 bp insertion: Rht-B1i-1 (with the 160 bp insertion and Rht-B1i-2 (without the 160 bp insertion. The promoter of Rht-B1i-1 contained 32 more possible cis-acting elements than Rht-B1a, including a unique auxin response element AUXREPSIAA4. Quantitative RT-PCR analysis indicated that the 160 bp insertion is likely to promote the transcription of the Rht-B1i-1 gene. The coleoptile lengths of wheat varieties treated with IAA, GA3, and IAA/GA3, combined with the histochemical staining of transgenic Arabidopsis containing the Rht-B1i-1 promoter, showed that the height-increasing effect of Rht-B1i-1 may be due to the synergistic action of IAA and GA3. These results augment our understanding of the regulatory mechanisms of Rht-1 in wheat and provide new genetic resources for wheat improvement.

BP's driving safety strategy

Energy Technology Data Exchange (ETDEWEB)

Herman, B. [BP Canada Energy Company, Calgary, AB (Canada)

2006-07-01

This presentation focused on why it is important to drive safely. It addressed driver fatigue as well as BP's global driving standard. The Standard applies to all BP employees and contractors that drive any vehicle on BP business and consists of 10 mandatory elements focusing on safety of the driver, the safety of the journey, and the safety of the vehicle. The driving standards focus on several themes, including skill and competency of the driver, safety of the journey, and safety of the vehicle. Fatigue causes more than 20 per cent of motorway accidents and is the most frequent cause of accidental death of truck drivers. The presentation also discussed vehicle data recorders, driving immersion, and Driving Safety Program results. Journey management, driver training, vehicle inspections and policies, and statistics on vehicle incidents were also provided. The presentation revealed that a lack of pre-trip journey management, inadequate training or recall of training, and not following safe driving practices were major contributors to incident occurrences. It also revealed that traveling on gravel or ice and avoiding wildlife were factors in many vehicle incidents. 1 tab., 1 fig.

AcEST: BP918019 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000108_F08 47 Adiantum capillus-veneris mRNA. clone: YMU001_000108_F08. BP918019 - Show BP91801... mRNA. clone: YMU001_000108_F08. Accession BP918019 Tissue type prothallium Developmental stage - Contig ID

InterProScan Result: BP116799 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP116799 BP116799_1_ORF2 D3F3F8C61868AD4C PANTHER PTHR11792 ARRESTIN 3.5e-15 T IPR000698 Arrestin Biological... Process: signal transduction (GO:0007165)|Biological Process: sensory perception (GO:0007600) ...

InterProScan Result: BP116799 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP116799 BP116799_1_ORF2 D3F3F8C61868AD4C PRINTS PR00309 ARRESTIN 6e-17 T IPR000698 Arrestin Biological... Process: signal transduction (GO:0007165)|Biological Process: sensory perception (GO:0007600) ...

Nucleoporin NUP153 guards genome integrity by promoting nuclear import of 53BP1

Czech Academy of Sciences Publication Activity Database

Moudrý, Pavel; Lukas, C.; Macůrek, Libor; Neumann, B.; Heriche, J.K.; Pepperkok, R.; Ellenberg, J.; Hodný, Zdeněk; Lukas, J.; Bartek, Jiří

2012-01-01

Roč. 19, č. 5 (2012), s. 798-807 ISSN 1350-9047 R&D Projects: GA ČR GA301/08/0353; GA ČR GAP301/10/1525; GA ČR GPP305/10/P420 Grant - others:7.RP EU(XE) CZ.1.05/2.1.00/01.0030 Institutional research plan: CEZ:AV0Z50520514 Keywords : DNA damage response * NUP153 * 53BP1 nuclear import Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.371, year: 2012

Purification, characterization and stability of barley grain peroxidase BP1, a new type of plant peroxidase

DEFF Research Database (Denmark)

Rasmussen, Christine B; Henriksen, Anette; Abelskov, A. Katrine

1997-01-01

peroxidase isoenzyme C (HRP C). However, when measuring the specific activity of BP 1 at pH 4.0 in the presence of 1 mM CaCl2, the enzyme was as competent as HRP C at neutral pH towards a variety of substrates (mM mg(-1) min(-1)): coniferyl alcohol (930+/-48), caffeic acid (795+/-53), ABTS (2,2(1)-azino...

AcEST: BP912612 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000020_H07 512 Adiantum capillus-veneris mRNA. clone: YMU001_000020_H07. BP912612 - Show BP912612... Clone id YMU001_000020_H07 Library YMU01 Length 512 Definition Adiantum capillus-vener...is mRNA. clone: YMU001_000020_H07. Accession BP912612 Tissue type prothallium Developmental stage - Contig I...se search programs, Nucleic Acids Res. 25:3389-3402. Query= BP912612|Adiantum cap...illus-veneris mRNA, clone: YMU001_000020_H07. (512 letters) Database: uniprot_sprot.fasta 412,525 sequences;

AcEST: BP912712 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000022_A07 476 Adiantum capillus-veneris mRNA. clone: YMU001_000022_A07. BP912712 - Show BP912712...is mRNA. clone: YMU001_000022_A07. Accession BP912712 Tissue type prothallium Developmental stage - Contig I...cleic Acids Res. 25:3389-3402. Query= BP912712|Adiantum capillus-veneris mRNA, cl...one: YMU001_000022_A07. (476 letters) Database: uniprot_sprot.fasta 412,525 sequences; 148,809,765 total let...8%), Positives = 39/69 (56%), Gaps = 4/69 (5%) Frame = +3 Query: 123 TSRRKSNHDQY--LPNYKVGTVHLLLGVKDQHLVSKIDI

CtBP1/BARS Gly172 → Glu mutant structure: Impairing NAD(H)-binding and dimerization

International Nuclear Information System (INIS)

Nardini, Marco; Valente, Carmen; Ricagno, Stefano; Luini, Alberto; Corda, Daniela; Bolognesi, Martino

2009-01-01

C-terminal binding proteins (CtBPs) are multi-functional proteins involved in nuclear transcriptional co-repression, Golgi membrane fission, and synaptic ribbon formation. Binding of NAD(H) to CtBPs promotes dimerization. CtBP dimers act as a scaffold for multimeric protein complex formation, thus bridging transcriptional repressors and their targets in the nucleus. Based on size-exclusion chromatography experiments and on the crystal structure of the NAD(H)-free G172E CtBP mutant, we show here that absence of NAD(H) induces flexibility/backbone conformational changes at the dimerization interface and at the CtBP interdomain region. The results presented shed first light on the correlation between NAD(H)-binding and functional CtBP dimerization.

ppGpp Controls Global Gene Expression in Light and in Darkness in S. elongatus

Directory of Open Access Journals (Sweden)

Anna M. Puszynska

2017-12-01

Full Text Available The bacterial and plant stringent response involves production of the signaling molecules guanosine tetraphosphate and guanosine pentaphosphate ((pppGpp, leading to global reorganization of gene expression. The function of the stringent response has been well characterized in stress conditions, but its regulatory role during unstressed growth is less studied. Here, we demonstrate that (pppGpp-deficient strains of S. elongatus have globally deregulated biosynthetic capacity, with increased transcription rate, translation rate, and cell size in unstressed conditions in light and impaired viability in darkness. Synthetic restoration of basal guanosine tetraphosphate (ppGpp levels is sufficient to recover transcriptional balance and appropriate cell size in light and to rescue viability in light/dark conditions, but it is insufficient to enable efficient dark-induced transcriptional shutdown. Our work underscores the importance of basal ppGpp signaling for regulation of cyanobacterial physiology in the absence of stress and for viability in energy-limiting conditions, highlighting that basal (pppGpp level is essential in cyanobacteria in the environmental light/dark cycle.

Alcohol-tolerant mutants of cyanobacterium Synechococcus elongatus PCC 7942 obtained by single-cell mutant screening system.

Science.gov (United States)

Arai, Sayuri; Hayashihara, Kayoko; Kanamoto, Yuki; Shimizu, Kazunori; Hirokawa, Yasutaka; Hanai, Taizo; Murakami, Akio; Honda, Hiroyuki

2017-08-01

Enhancement of alcohol tolerance in microorganisms is an important strategy for improving bioalcohol productivity. Although cyanobacteria can be used as a promising biocatalyst to produce various alcohols directly from CO 2 , low productivity, and low tolerance against alcohols are the main issues to be resolved. Nevertheless, to date, a mutant with increasing alcohol tolerance has rarely been reported. In this study, we attempted to select isopropanol (IPA)-tolerant mutants of Synechococcus elongatus PCC 7942 using UV-C-induced random mutagenesis, followed by enrichment of the tolerant candidates in medium containing 10 g/L IPA and screening of the cells with a high growth rate in the single cell culture system in liquid medium containing 10 g/L IPA. We successfully acquired the most tolerant strain, SY1043, which maintains the ability to grow in medium containing 30 g/L IPA. The photosynthetic oxygen-evolving activities of SY1043 were almost same in cells after 72 h incubation under light with or without 10 g/L IPA, while the activity of the wild-type was remarkably decreased after the incubation with IPA. SY1043 also showed higher tolerance to ethanol, 1-butanol, isobutanol, and 1-pentanol than the wild type. These results suggest that SY1043 would be a promising candidate to improve alcohol production using cyanobacteria. Biotechnol. Bioeng. 2017;114: 1771-1778. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

AcEST: BP921212 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000147_A09 361 Adiantum capillus-veneris mRNA. clone: YMU001_000147_A09. BP921212 - Show BP921212...is mRNA. clone: YMU001_000147_A09. Accession BP921212 Tissue type prothallium Developmental stage - Contig I...protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP921212|Adiantum capillus-veneris... mRNA, clone: YMU001_000147_A09. (361 letters) Database: uniprot_sprot.fasta 412,...itol-4,5-bisphosphate 3-ki... 30 2.9 sp|O14338|YB33_SCHPO Uncharacterized serine-rich protein C2F12.0... 29

Serum levels of IGF-1 and IGF-BP3 are associated with event-free survival in adult Ewing sarcoma patients treated with chemotherapy

Directory of Open Access Journals (Sweden)

de Groot S

2017-06-01

Full Text Available Stefanie de Groot,1 Hans Gelderblom,1 Marta Fiocco,2,3 Judith VMG Bovée,4 Jacobus JM van der Hoeven,1 Hanno Pijl,5 Judith R Kroep1 1Department of Medical Oncology, 2Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, 3Mathematical Department, Leiden University, 4Department of Pathology, 5Department of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands Background: Activation of the insulin-like growth factor 1 (IGF-1 pathway is involved in cell growth and proliferation and is associated with tumorigenesis, tumor progression, and therapy resistance in solid tumors. We examined whether variability in serum levels of IGF-1, IGF-2, and IGF-binding protein 3 (IGF-BP3 can predict event-free survival (EFS and overall survival (OS in Ewing sarcoma patients treated with chemotherapy.Patients and methods: Serum levels of IGF-1, IGF-2, and IGF-BP3 of 22 patients with localized or metastasized Ewing sarcoma treated with six cycles of vincristine/ifosfamide/doxorubicin/etoposide (VIDE chemotherapy were recorded. Baseline levels were compared with presixth cycle levels using paired t-tests and were tested for associations with EFS and OS. Continuous variables were dichotomized according to the Contal and O’Quigley procedure. Survival analyses were performed using Cox regression analysis.Results: High baseline IGF-1 and IGF-BP3 serum levels were associated with EFS (hazard ratio [HR] 0.075, 95% confidence interval [CI] 0.009–0.602 and HR 0.090, 95% CI 0.011–0.712, respectively in univariate and multivariate analyses (HR 0.063, 95% CI 0.007–0.590 and HR 0.057, 95% CI 0.005–0.585, respectively. OS was improved, but this was not statistically significant. IGF-BP3 and IGF-2 serum levels increased during treatment with VIDE chemotherapy (P=0.055 and P=0.023, respectively.Conclusion: High circulating serum levels of IGF-1 and IGF-BP3 and the molar ratio of IGF-1:IGF-BP3 serum levels were associated

InterProScan Result: BP117067 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP117067 BP117067_1_ORF2 D483359C05197373 PFAM PF00067 p450 6e-05 T IPR001128 Cytochrome P450 Molecular... Function: monooxygenase activity (GO:0004497)|Molecular Function: iron ion binding (GO:0005506)|Molecular... Function: electron carrier activity (GO:0009055)|Molecular Function: heme binding (GO:0020037) ...

AcEST: BP912112 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU001_000015_C08 546 Adiantum capillus-veneris mRNA. clone: YMU001_000015_C08. BP912112 - Show BP912112...is mRNA. clone: YMU001_000015_C08. Accession BP912112 Tissue type prothallium Developmental stage - Contig I...Arabidopsis thaliana Align length 171 Score (bit) 121.0 E-value 3.0e-27 Report BLASTX 2.2.19 [Nov-02-2008] R... protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= BP912112|Adiantum capillus-veneri...s mRNA, clone: YMU001_000015_C08. (546 letters) Database: uniprot_sprot.fasta 412,525 sequences; 148,809,765

RanBP2 modulates Cox11 and hexokinase I activities and haploinsufficiency of RanBP2 causes deficits in glucose metabolism.

Directory of Open Access Journals (Sweden)

Azamat Aslanukov

2006-10-01

Full Text Available The Ran-binding protein 2 (RanBP2 is a large multimodular and pleiotropic protein. Several molecular partners with distinct functions interacting specifically with selective modules of RanBP2 have been identified. Yet, the significance of these interactions with RanBP2 and the genetic and physiological role(s of RanBP2 in a whole-animal model remain elusive. Here, we report the identification of two novel partners of RanBP2 and a novel physiological role of RanBP2 in a mouse model. RanBP2 associates in vitro and in vivo and colocalizes with the mitochondrial metallochaperone, Cox11, and the pacemaker of glycolysis, hexokinase type I (HKI via its leucine-rich domain. The leucine-rich domain of RanBP2 also exhibits strong chaperone activity toward intermediate and mature folding species of Cox11 supporting a chaperone role of RanBP2 in the cytosol during Cox11 biogenesis. Cox11 partially colocalizes with HKI, thus supporting additional and distinct roles in cell function. Cox11 is a strong inhibitor of HKI, and RanBP2 suppresses the inhibitory activity of Cox11 over HKI. To probe the physiological role of RanBP2 and its role in HKI function, a mouse model harboring a genetically disrupted RanBP2 locus was generated. RanBP2(-/- are embryonically lethal, and haploinsufficiency of RanBP2 in an inbred strain causes a pronounced decrease of HKI and ATP levels selectively in the central nervous system. Inbred RanBP2(+/- mice also exhibit deficits in growth rates and glucose catabolism without impairment of glucose uptake and gluconeogenesis. These phenotypes are accompanied by a decrease in the electrophysiological responses of photosensory and postreceptoral neurons. Hence, RanBP2 and its partners emerge as critical modulators of neuronal HKI, glucose catabolism, energy homeostasis, and targets for metabolic, aging disorders and allied neuropathies.

RanBP2 modulates Cox11 and hexokinase I activities and haploinsufficiency of RanBP2 causes deficits in glucose metabolism.

Science.gov (United States)

Aslanukov, Azamat; Bhowmick, Reshma; Guruju, Mallikarjuna; Oswald, John; Raz, Dorit; Bush, Ronald A; Sieving, Paul A; Lu, Xinrong; Bock, Cheryl B; Ferreira, Paulo A

2006-10-01

The Ran-binding protein 2 (RanBP2) is a large multimodular and pleiotropic protein. Several molecular partners with distinct functions interacting specifically with selective modules of RanBP2 have been identified. Yet, the significance of these interactions with RanBP2 and the genetic and physiological role(s) of RanBP2 in a whole-animal model remain elusive. Here, we report the identification of two novel partners of RanBP2 and a novel physiological role of RanBP2 in a mouse model. RanBP2 associates in vitro and in vivo and colocalizes with the mitochondrial metallochaperone, Cox11, and the pacemaker of glycolysis, hexokinase type I (HKI) via its leucine-rich domain. The leucine-rich domain of RanBP2 also exhibits strong chaperone activity toward intermediate and mature folding species of Cox11 supporting a chaperone role of RanBP2 in the cytosol during Cox11 biogenesis. Cox11 partially colocalizes with HKI, thus supporting additional and distinct roles in cell function. Cox11 is a strong inhibitor of HKI, and RanBP2 suppresses the inhibitory activity of Cox11 over HKI. To probe the physiological role of RanBP2 and its role in HKI function, a mouse model harboring a genetically disrupted RanBP2 locus was generated. RanBP2(-/-) are embryonically lethal, and haploinsufficiency of RanBP2 in an inbred strain causes a pronounced decrease of HKI and ATP levels selectively in the central nervous system. Inbred RanBP2(+/-) mice also exhibit deficits in growth rates and glucose catabolism without impairment of glucose uptake and gluconeogenesis. These phenotypes are accompanied by a decrease in the electrophysiological responses of photosensory and postreceptoral neurons. Hence, RanBP2 and its partners emerge as critical modulators of neuronal HKI, glucose catabolism, energy homeostasis, and targets for metabolic, aging disorders and allied neuropathies.

Inhibition of 53BP1: Potential for Restoring Homologous Recombination In Ovarian Cancer Cells

Science.gov (United States)

2017-08-01

likely that this approach will be useful to other scientists in the DNA damage response field who wish to probe how other proteins recognize...Regulation of 53BP1 recruitment to DNA damage sites. This is an invited Extra View article to be published in the journal Nucleus. Federal support will...2 and 3. Funding Support: Mayo Clinic Name: James Thompson, Ph.D. Project Role: Research Scientist Researcher Identifier (e.g

Diversidade genética de três estoques de piapara (Leporinus elongatus, utilizando RAPD = Genetic diversity of three stocks of piapara (Leporinus elongatus, using RAPD

Directory of Open Access Journals (Sweden)

Patrícia Cristina Gomes

2008-04-01

Full Text Available Recentemente a produção aquícola brasileira tem apresentado grandeprogresso. Dentre as espécies nativas cultivadas no Brasil, a piapara (Leporinus elongatus tem sido amplamente preconizada. Com objetivo de avaliar os programas de repovoamento, foram analisadas a variabilidade e a divergência genética de três estoques de piapara com a técnica de RAPD (Random Amplified Polymorphic. O primeiro estoque pertence à Estação de Aquicultura e Hidrologia da Duke Energy International (A; o segundo, à piscicultura de Rolândia (B e o terceiro, ao Programa de Repovoamento dos Rios do Paraná (C. Os dezprimers para RAPD utilizados produziram 105 fragmentos polimórficos, conferindo um polimorfismo de 98,1% para os três estoques avaliados. A porcentagem de locos polimórficos e índice de Shannon foi superior para o estoque A. Porém, todos valores foram elevados, indicando alta diversidade intrapopulacional. Os valores de Gst indicam que houvebaixa diferenciação genética entre os estoques A x B e moderada diferenciação entre os demais. O Nm foi maior entre os estoques A x B. A distância genética e o dendrograma indicam que os estoques A x B são menos distantes geneticamente.Latelly, aquiculture production in Brazil has made great strides. Among the native species cultivated in Brazil, piapara (Leporinus elogatus has been widely praised. With the objective of evaluating restocking programs, the variability and genetic divergence ofthree piapara stocks were analyzed using the RAPD (Random Amplified Polymorphic DNA technique. The first stock belongs to the Aquiculture and Hydrology Station of Duke Energy International (A; the second one belongs to a fish farm in the city of Rolândia(B; and the third to the River Restocking Program of Paraná (C. The ten primers used for RAPD produced 105 polymorphic loci, conferring a polymorphism of 98.1% for the three evaluated stocks. Polymorphic loci percentage and Shannon index were higher for stock A

Positive effects on hematological and biochemical imbalances in patients with metastatic breast cancer stage IV, of BP-C1, a new anticancer substance

Directory of Open Access Journals (Sweden)

Lindkær-Jensen S

2015-03-01

Full Text Available Steen Lindkær-Jensen,1 Stig Larsen,2 Nina Habib-Lindkær-Jensen,1 Hans E Fagertun3 1Department of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College, London, UK; 2Center of Epidemiology and Biostatistics, Faculty of Veterinary Medicine, University of Life Science, Oslo, Norway; 3Meddoc Research AS, Skjetten, Norway Abstract: A benzene-poly-carboxylic acid complex with cis-diammineplatinum(II dihydrocholride, BP-C1 is currently used in clinical trials in treating metastatic breast cancer. BP-C1 controls tumor growth with a few mild side-effects, improving quality of life.Methods: The data consisted of prospectively collected laboratory results from 47 patients in two controlled clinical trials of daily intramuscular injections of BP-C1 for 32 days. Study I was performed as an open, nonrandomized, Phase I dose–response, multicenter study with a three-level, between-patient, response surface pathway design. The second study was a randomized, double-blind, and placebo-controlled, multicenter study with a stratified semi-crossover design.Results: Hemoglobin (Hb and hematocrit (Hct increased significantly (P<0.01 during BP-C1 treatment, while red blood cell (RBC count increased but not significantly. The most pronounced increase in Hb, RBC, Hct, and white blood cell (WBC was in anemic patients (P≤0.01. WBC count and neutrophils increased significantly (P=0.01 in the overall data. WBCs and neutrophils (P<0.01, eosinophils (P=0.05 and monocytes (P<0.01 increased significantly and markedly in patients with lowest baseline levels. Additionally, low levels of thrombocytes significantly increased. No changes in liver parameters, amylase, glucose, creatinine, or albumin, were detected except for albumin in the subgroup with low baseline levels, where levels increased significantly (P=0.04. An increase in K+, Ca2+, and PO43- was most pronounced in patients with low baseline levels (P≤0.02. A similar pattern detected for Mg2+, prothrombin

Binding of complement proteins C1q and C4bp to serum amyloid P component (SAP) in solid contra liquid phase

DEFF Research Database (Denmark)

Sørensen, Inge Juul; Nielsen, EH; Andersen, Ove

1996-01-01

Serum amyloid P component (SAP), a member of the conserved pentraxin family of plasma proteins, binds calcium dependently to its ligands. The authors investigated SAPs interaction with the complement proteins C4b binding protein (C4bp) and C1q by ELISA, immunoelectrophoresis and electron microscopy....... Binding of these proteins to SAP was demonstrated when SAP was immobilized using F(ab')2 anti-SAP, but not when SAP reacted with these proteins in liquid phase; thus the binding to human SAP was markedly phase state dependent. Presaturation of solid phase SAP with heparin, which binds SAP with high...... affinity, did not interfere with the subsequent binding of C4bp or C1q to SAP. In contrast, collagen I and IV showed partial competition with the binding of C1q to SAP. Using fresh serum, immobilized native SAP bound C4bp whereas binding of C1q/C1 could not be demonstrated. Altogether the results indicate...

Intensive Versus Standard Blood Pressure Control in SPRINT-Eligible Participants of ACCORD-BP.

Science.gov (United States)

Buckley, Leo F; Dixon, Dave L; Wohlford, George F; Wijesinghe, Dayanjan S; Baker, William L; Van Tassell, Benjamin W

2017-12-01

We sought to determine the effect of intensive blood pressure (BP) control on cardiovascular outcomes in participants with type 2 diabetes mellitus (T2DM) and additional risk factors for cardiovascular disease (CVD). This study was a post hoc, multivariate, subgroup analysis of ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure) participants. Participants were eligible for the analysis if they were in the standard glucose control arm of ACCORD-BP and also had the additional CVD risk factors required for SPRINT (Systolic Blood Pressure Intervention Trial) eligibility. We used a Cox proportional hazards regression model to compare the effect of intensive versus standard BP control on CVD outcomes. The "SPRINT-eligible" ACCORD-BP participants were pooled with SPRINT participants to determine whether the effects of intensive BP control interacted with T2DM. The mean baseline Framingham 10-year CVD risk scores were 14.5% and 14.8%, respectively, in the intensive and standard BP control groups. The mean achieved systolic BP values were 120 and 134 mmHg in the intensive and standard BP control groups ( P control reduced the composite of CVD death, nonfatal myocardial infarction (MI), nonfatal stroke, any revascularization, and heart failure (hazard ratio 0.79; 95% CI 0.65-0.96; P = 0.02). Intensive BP control also reduced CVD death, nonfatal MI, and nonfatal stroke (hazard ratio 0.69; 95% CI 0.51-0.93; P = 0.01). Treatment-related adverse events occurred more frequently in participants receiving intensive BP control (4.1% vs. 2.1%; P = 0.003). The effect of intensive BP control on CVD outcomes did not differ between patients with and without T2DM ( P > 0.62). Intensive BP control reduced CVD outcomes in a cohort of participants with T2DM and additional CVD risk factors. © 2017 by the American Diabetes Association.

Lentiviral Vpx accessory factor targets VprBP/DCAF1 substrate adaptor for cullin 4 E3 ubiquitin ligase to enable macrophage infection.

Directory of Open Access Journals (Sweden)

Smita Srivastava

2008-05-01

Full Text Available Vpx is a small virion-associated adaptor protein encoded by viruses of the HIV-2/SIVsm lineage of primate lentiviruses that enables these viruses to transduce monocyte-derived cells. This probably reflects the ability of Vpx to overcome an as yet uncharacterized block to an early event in the virus life cycle in these cells, but the underlying mechanism has remained elusive. Using biochemical and proteomic approaches, we have found that Vpx protein of the pathogenic SIVmac 239 strain associates with a ternary protein complex comprising DDB1 and VprBP subunits of Cullin 4-based E3 ubiquitin ligase, and DDA1, which has been implicated in the regulation of E3 catalytic activity, and that Vpx participates in the Cullin 4 E3 complex comprising VprBP. We further demonstrate that the ability of SIVmac as well as HIV-2 Vpx to interact with VprBP and its associated Cullin 4 complex is required for efficient reverse transcription of SIVmac RNA genome in primary macrophages. Strikingly, macrophages in which VprBP levels are depleted by RNA interference resist SIVmac infection. Thus, our observations reveal that Vpx interacts with both catalytic and regulatory components of the ubiquitin proteasome system and demonstrate that these interactions are critical for Vpx ability to enable efficient SIVmac replication in primary macrophages. Furthermore, they identify VprBP/DCAF1 substrate receptor for Cullin 4 E3 ubiquitin ligase and its associated protein complex as immediate downstream effector of Vpx for this function. Together, our findings suggest a model in which Vpx usurps VprBP-associated Cullin 4 ubiquitin ligase to enable efficient reverse transcription and thereby overcome a block to lentivirus replication in monocyte-derived cells, and thus provide novel insights into the underlying molecular mechanism.

Expression of the Transcription Factor E4BP4 in Human Basophils

DEFF Research Database (Denmark)

Jensen, Bettina Margrethe; Gohr, Maria; Poulsen, Lars Kærgaard

2014-01-01

Rationale The cytokine IL-3 plays an important role for human basophil development, function and survival. IL-3 is also reported to induce the expression of the transcription factor E4BP4, but it is not known whether E4BP4 is expressed in basophils and influences basophil responsiveness. The aim...... by Alcian blue. RNA was extracted (0.005-0.02 µg RNA from 0.5 - 1 x 106 cells), and the corresponding cDNA analyzed by real-time PCR where E4BP4 expression was calculated as 2-(CT(E4BP4) - CT(β-actin)). E4BP4 protein expression was visualized in basophil lysates (107 cells/ml) by Western blot followed...... the transcription factor E4BP4 which might have an impact on basophil histamine release....

BP-C1 in the treatment of patients with stage IV breast cancer: a randomized, double-blind, placebo-controlled multicenter study and an additional open-label treatment phase

Directory of Open Access Journals (Sweden)

Larsen S

2014-11-01

Full Text Available Stig Larsen,1 Kritiya Butthongkomvong,2 Alexey Manikhas,3 Ekaterina Trishkina,4 Elena Poddubuskaya,5 Marina Matrosova,6 Vichien Srimuninnimit,7 Steen Lindkær-Jensen81Department of Controlled Clinical Trials and Biostatistics, Centre for Epidemiology and Biostatistics, University of Life Science, Oslo, Norway; 2Udonthani Cancer Hospital, Udonthani, Thailand; 3Department of Oncology, City Clinical Oncology, Dispensary, St Petersburg, Russia; 4Department of Oncology, Leningrad Regional Oncology Centre, St Petersburg, Russia; 5Department of Oncology, Unit of Russian Academy of Medical Science, Moscow, Russia; 6Department of Oncology, N Novgorod Regional Oncology Dispensary, Novgorod, Russia; 7Division of Medical Oncology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 8Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, UKAbstract: The aims were to compare the efficacy and tolerability of a new benzene-poly-carboxylic acids complex with cis-diammineplatinum (II dichloride (BP-C1 versus placebo and to investigate the long-term tolerability of BP-C1 in the treatment of patients with metastatic breast cancer.Material and methods: A randomized, double-blind, placebo-controlled multicenter study was performed with a semi-crossover design. Patients allocated to placebo switched to BP-C1 after 32 days of treatment. Patients who completed 32 days of BP-C1 treatment were offered the opportunity to continue on BP-C1 for an additional 32 days in an open-label extension. Patients were then followed up for another 28 days. Thirty patients were given daily intramuscular injections of 0.035 mg/kg of body weight BP-C1 or placebo for 32 days. Biochemistry, hematology, National Cancer Institute Common Terminology Criteria for Adverse Events (CTC-NCI, European Organisation for Research and Treatment of Cancer quality of life questionnaire (QOL-C30 and the breast-cancer–specific BR23 data were recorded at

EST Table: BP121749 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP121749 ceN-5256 10/09/28 100 %/172 aa ref|NP_001036831.1| saposin-related [Bombyx...|GB16561-PA 10/09/10 44 %/178 aa gi|91077504|ref|XP_966852.1| PREDICTED: similar to saposin isoform 1 [Tribolium castaneum] FS791050 ceN- ...

EST Table: BP121763 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP121763 ceN-5273 10/09/28 99 %/184 aa ref|NP_001036831.1| saposin-related [Bombyx ...GB16561-PA 10/09/10 43 %/192 aa gi|91077504|ref|XP_966852.1| PREDICTED: similar to saposin isoform 1 [Tribolium castaneum] FS791050 ceN- ...

mTORC1 Targets the Translational Repressor 4E-BP2, but Not S6 Kinase 1/2, to Regulate Neural Stem Cell Self-Renewal In Vivo

Directory of Open Access Journals (Sweden)

Nathaniel W. Hartman

2013-10-01

Full Text Available The mammalian target of rapamycin complex 1 (mTORC1 integrates signals important for cell growth, and its dysregulation in neural stem cells (NSCs is implicated in several neurological disorders associated with abnormal neurogenesis and brain size. However, the function of mTORC1 on NSC self-renewal and the downstream regulatory mechanisms are ill defined. Here, we found that genetically decreasing mTORC1 activity in neonatal NSCs prevented their differentiation, resulting in reduced lineage expansion and aborted neuron production. Constitutive activation of the translational repressor 4E-BP1, which blocked cap-dependent translation, had similar effects and prevented hyperactive mTORC1 induction of NSC differentiation and promoted self-renewal. Although 4E-BP2 knockdown promoted NSC differentiation, p70 S6 kinase 1 and 2 (S6K1/S6K2 knockdown did not affect NSC differentiation but reduced NSC soma size and prevented hyperactive mTORC1-induced increase in soma size. These data demonstrate a crucial role of mTORC1 and 4E-BP for switching on and off cap-dependent translation in NSC differentiation.

Tunneling in BP-MoS2 heterostructure

Science.gov (United States)

Liu, Xiaochi; Qu, Deshun; Kim, Changsik; Ahmed, Faisal; Yoo, Won Jong

Tunnel field effect transistor (TFET) is considered to be a leading option for achieving SS mV/dec. In this work, black phosphorus (BP) and molybdenum disulfide (MoS2) heterojunction devices are fabricated. We find that thin BP flake and MoS2 form normal p-n junctions, tunneling phenomena can be observed when BP thickness increases to certain level. PEO:CsClO4 is applied on the surface of the device together with a side gate electrode patterned together with source and drain electrodes. The Fermi level of MoS2 on top of BP layer can be modulated by the side gating, and this enables to vary the MoS2-BP tunnel diode property from off-state to on-state. Since tunneling is the working mechanism of MoS2-BP junction, and PEO:CsClO4\\ possesses ultra high dielectric constant and small equivalent oxide thickness (EOT), a low SS of 55 mV/dec is obtained from MoS2-BP TFET. This work was supported by the Global Research Laboratory and Global Frontier R&D Programs at the Center for Hybrid Interface Materials, both funded by the Ministry of Science, ICT & Future Planning via the National Research Foundation of Korea (NRF).

BP, Cardiovascular Disease, and Death in the Folic Acid for Vascular Outcome Reduction in Transplantation Trial

Science.gov (United States)

John, Alin; Weir, Matthew R.; Smith, Stephen R.; Hunsicker, Lawrence; Kasiske, Bertram L.; Kusek, John W.; Bostom, Andrew; Ivanova, Anastasia; Levey, Andrew S.; Solomon, Scott; Pesavento, Todd; Weiner, Daniel E.

2014-01-01

The optimal BP level in kidney transplant recipients remains uncertain. This post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial cohort assessed associations of BP with a pooled cardiovascular disease (CVD) outcome and with all-cause mortality. In 3474 prevalent kidney transplant patients, mean age was 52±9 years, 63% were men, 76% were white, 20% had a history of CVD, 40% had a history of diabetes mellitus, and the median time since transplant was 4.1 years (25th to 75th percentiles, 1.7–7.4); mean systolic BP was 136±20 mmHg and mean diastolic BP was 79±12 mmHg. There were 497 CVD events and 406 deaths. After adjustment for demographic and transplant characteristics and CVD risk factors, each 20-mmHg increase in baseline systolic BP associated with a 32% increase in subsequent CVD risk (hazard ratio [HR], 1.32; 95% confidence interval [95% CI], 1.19 to 1.46) and a 13% increase in mortality risk (HR, 1.13; 95% CI, 1.01 to 1.27). Similarly, after adjustment, at diastolic BP levels70 mmHg, there was no significant relationship between diastolic BP and outcomes. Higher systolic BP strongly and independently associated with increased risk of CVD and all-cause mortality, without evidence of a J shape, whereas only lower levels of diastolic BP associated with increased risk of CVD and death in this trial. PMID:24627349

EST Table: BP117517 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP117517 ce--0464 10/09/28 63 %/173 aa ref|XP_002092422.1| GE14184 [Drosophila yakuba] gb|EDW92134.1| GE14...184 [Drosophila yakuba] 10/08/28 63 %/173 aa FBpp0259194|DyakGE14184-PA 10/08/28 35 %

Direct Binding to Replication Protein A (RPA)-coated Single-stranded DNA Allows Recruitment of the ATR Activator TopBP1 to Sites of DNA Damage*

Science.gov (United States)

Acevedo, Julyana; Yan, Shan; Michael, W. Matthew

2016-01-01

A critical event for the ability of cells to tolerate DNA damage and replication stress is activation of the ATR kinase. ATR activation is dependent on the BRCT (BRCA1 C terminus) repeat-containing protein TopBP1. Previous work has shown that recruitment of TopBP1 to sites of DNA damage and stalled replication forks is necessary for downstream events in ATR activation; however, the mechanism for this recruitment was not known. Here, we use protein binding assays and functional studies in Xenopus egg extracts to show that TopBP1 makes a direct interaction, via its BRCT2 domain, with RPA-coated single-stranded DNA. We identify a point mutant that abrogates this interaction and show that this mutant fails to accumulate at sites of DNA damage and that the mutant cannot activate ATR. These data thus supply a mechanism for how the critical ATR activator, TopBP1, senses DNA damage and stalled replication forks to initiate assembly of checkpoint signaling complexes. PMID:27129245

Oxygen-dependent acetylation and dimerization of the corepressor CtBP2 in neural stem cells

International Nuclear Information System (INIS)

Karaca, Esra; Lewicki, Jakub; Hermanson, Ola

2015-01-01

The transcriptional corepressor CtBP2 is essential for proper development of the nervous system. The factor exerts its repression by interacting in complexes with chromatin-modifying factors such as histone deacetylases (HDAC) 1/2 and the histone demethylase LSD1/KDM1. Notably, the histone acetyl transferase p300 acetylates CtBP2 and this is an important regulatory event of the activity and subcellular localization of the protein. We recently demonstrated an essential role for CtBPs as sensors of microenvironmental oxygen levels influencing the differentiation potential of neural stem cells (NSCs), but it is not known whether oxygen levels influence the acetylation levels of CtBP factors. Here we show by using proximity ligation assay (PLA) that CtBP2 acetylation levels increased significantly in undifferentiated, proliferating NSCs under hypoxic conditions. CtBP2 interacted with the class III HDAC Sirt1 but this interaction was unaltered in hypoxic conditions, and treatment with the Sirt1 inhibitor Ex527 did not result in any significant change in total CtBP2 acetylation levels. Instead, we revealed a significant decrease in PLA signal representing CtBP2 dimerization in NSCs under hypoxic conditions, negatively correlating with the acetylation levels. Our results suggest that microenvironmental oxygen levels influence the dimerization and acetylation levels, and thereby the activity, of CtBP2 in proliferating NSCs

Oxygen-dependent acetylation and dimerization of the corepressor CtBP2 in neural stem cells

Energy Technology Data Exchange (ETDEWEB)

Karaca, Esra; Lewicki, Jakub; Hermanson, Ola, E-mail: Ola.Hermanson@ki.se

2015-03-01

The transcriptional corepressor CtBP2 is essential for proper development of the nervous system. The factor exerts its repression by interacting in complexes with chromatin-modifying factors such as histone deacetylases (HDAC) 1/2 and the histone demethylase LSD1/KDM1. Notably, the histone acetyl transferase p300 acetylates CtBP2 and this is an important regulatory event of the activity and subcellular localization of the protein. We recently demonstrated an essential role for CtBPs as sensors of microenvironmental oxygen levels influencing the differentiation potential of neural stem cells (NSCs), but it is not known whether oxygen levels influence the acetylation levels of CtBP factors. Here we show by using proximity ligation assay (PLA) that CtBP2 acetylation levels increased significantly in undifferentiated, proliferating NSCs under hypoxic conditions. CtBP2 interacted with the class III HDAC Sirt1 but this interaction was unaltered in hypoxic conditions, and treatment with the Sirt1 inhibitor Ex527 did not result in any significant change in total CtBP2 acetylation levels. Instead, we revealed a significant decrease in PLA signal representing CtBP2 dimerization in NSCs under hypoxic conditions, negatively correlating with the acetylation levels. Our results suggest that microenvironmental oxygen levels influence the dimerization and acetylation levels, and thereby the activity, of CtBP2 in proliferating NSCs.

Role of G3BP1 in glucocorticoid receptor-mediated microRNA-15b and microRNA-23a biogenesis in endothelial cells

KAUST Repository

Kwok, Hoi-Hin

2017-05-18

MicroRNAs (miRNAs) are a family of non-coding RNAs that play crucial roles in regulating various normal cellular responses. Recent studies revealed that the canonical miRNA biogenesis pathway is subject to sophisticated regulation. Hormonal control of miRNA biogenesis by androgen and estrogen has been demonstrated, but the direct effects of the glucocorticoid receptor (GR) on miRNA biogenesis are unknown. This study revealed the role of GR in miRNA maturation. We showed that two GR agonists, dexamethasone and ginsenoside-Rg1 rapidly suppressed the expression of mature miR-15b, miR-23a, and miR-214 in human endothelial cells. RNA pulldown coupled with proteomic analysis identified GTPase-activating protein (SH3 domain) binding protein 1 (G3BP1) as one of the RNA-binding proteins mediating GR-regulated miRNA maturation. Activated GR induced phosphorylation of v-AKT Murine Thymoma Viral Oncogene Homologue (AKT) kinase, which in turn phosphorylated and promoted nuclear translocation of G3BP1. The nuclear G3BP1 bound to the G3BP1 consensus sequence located on primary miR-15b~16-2 and miR-23a~27a~24-2 to inhibit their maturation. The findings from this study have advanced our understanding of the non-genomic effects of GR in the vascular system.

EST Table: BP124521 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP124521 epV32477 10/09/28 59 %/164 aa dbj|BAA86911.1| homologue of Sarcophaga 26,29kDa proteinase [Periplan...eta americana] 10/08/29 55 %/163 aa FBpp0160847|DmojGI11630-PA 10/08/28 n.h 10/09/1

EST Table: BP123885 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP123885 epV31590 10/09/28 57 %/174 aa dbj|BAA86911.1| homologue of Sarcophaga 26,29kDa proteinase [Periplan...eta americana] 10/08/29 55 %/163 aa FBpp0160847|DmojGI11630-PA 10/08/28 n.h 10/09/1

EST Table: BP125106 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP125106 fbpv0387 10/09/28 58 %/165 aa dbj|BAA86911.1| homologue of Sarcophaga 26,29kDa proteinase [Periplan...eta americana] 10/08/29 56 %/165 aa FBpp0212871|DsimGD14469-PA 10/08/28 n.h 10/09/1

EST Table: BP125521 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP125521 fbpv0944 10/09/28 59 %/165 aa dbj|BAA86911.1| homologue of Sarcophaga 26,29kDa proteinase [Periplan...eta americana] 10/08/29 56 %/164 aa FBpp0160847|DmojGI11630-PA 10/08/28 n.h 10/09/1

EST Table: BP125005 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP125005 fbpv0197 10/09/28 58 %/185 aa dbj|BAA86911.1| homologue of Sarcophaga 26,29kDa proteinase [Periplan...eta americana] 10/08/29 58 %/173 aa FBpp0160847|DmojGI11630-PA 10/08/28 n.h 10/09/1

Sleep-time BP: prognostic marker of type 2 diabetes and therapeutic target for prevention.

Science.gov (United States)

Hermida, Ramón C; Ayala, Diana E; Mojón, Artemio; Fernández, José R

2016-02-01

We investigated the prognostic value of clinic and ambulatory BP (ABP) to predict new-onset diabetes and whether risk reduction is related to the progressive decrease of clinic BP or awake or asleep ABP. We prospectively evaluated 2,656 individuals without diabetes, 1,292 men and 1,364 women, 50.6 ± 14.3 years of age, with baseline BP ranging from normotension to hypertension according to ABP criteria. At baseline and annually (more frequently if hypertension treatment was adjusted based on ABP) thereafter, ABP and physical activity (wrist actigraphy) were simultaneously monitored for 48 h to accurately derive the awake and asleep BP means. During a 5.9-year median follow-up, 190 participants developed type 2 diabetes. The asleep systolic ABP mean was the most significant predictor of new-onset diabetes in a Cox proportional-hazard model adjusted for age, waist circumference, glucose, chronic kidney disease (CKD) and hypertension treatment. Daytime clinic BP and awake or 48 h ABP mean had no predictive value when corrected by the asleep ABP mean. Analyses of BP changes during follow-up revealed a 30% reduction in the risk of new-onset diabetes per 1-SD decrease in asleep systolic ABP mean, independent of changes in clinic BP or awake or 48 h ABP means. Sleep-time BP is a highly significant independent prognostic marker for new-onset diabetes. Alteration in sleep-time BP regulation seems to precede, rather than follow, the development of new-onset diabetes. Most important, lowering asleep BP, a novel therapeutic target requiring ABP evaluation, could be a significant method for reducing new-onset diabetes risk.

BP180 dysfunction triggers spontaneous skin inflammation in mice.

Science.gov (United States)

Zhang, Yang; Hwang, Bin-Jin; Liu, Zhen; Li, Ning; Lough, Kendall; Williams, Scott E; Chen, Jinbo; Burette, Susan W; Diaz, Luis A; Su, Maureen A; Xiao, Shengxiang; Liu, Zhi

2018-06-04

BP180, also known as collagen XVII, is a hemidesmosomal component and plays a key role in maintaining skin dermal/epidermal adhesion. Dysfunction of BP180, either through genetic mutations in junctional epidermolysis bullosa (JEB) or autoantibody insult in bullous pemphigoid (BP), leads to subepidermal blistering accompanied by skin inflammation. However, whether BP180 is involved in skin inflammation remains unknown. To address this question, we generated a BP180-dysfunctional mouse strain and found that mice lacking functional BP180 (termed Δ NC16A ) developed spontaneous skin inflammatory disease, characterized by severe itch, defective skin barrier, infiltrating immune cells, elevated serum IgE levels, and increased expression of thymic stromal lymphopoietin (TSLP). Severe itch is independent of adaptive immunity and histamine, but dependent on increased expression of TSLP by keratinocytes. In addition, a high TSLP expression is detected in BP patients. Our data provide direct evidence showing that BP180 regulates skin inflammation independently of adaptive immunity, and BP180 dysfunction leads to a TSLP-mediated itch. The newly developed mouse strain could be a model for elucidation of disease mechanisms and development of novel therapeutic strategies for skin inflammation and BP180-related skin conditions.

BP - bisnis põhjas? / Erik Aru

Index Scriptorium Estoniae

Aru, Erik

2010-01-01

Seoses Mehhiko lahe naftareostusega ootab BP-d kuni 21 mld. dollari suurune trahv, kahjude hüvitamiseks peab BP müüma osa oma varast. Ekspertide hinnangul tähendavad Mehhiko lahe sündmused suuri muutusi kogu naftaäris

Purification, crystallization and preliminary X-ray diffraction of the G3BP1 NTF2-like domain

DEFF Research Database (Denmark)

Vognsen, Tina; Möller, Ingvar Rúnar; Kristensen, Ole

2011-01-01

The nuclear transport factor 2-like (NTF2-like) domain of human G3BP1 was subcloned, overexpressed in Escherichia coli and purified. Crystals were obtained using the hanging-drop vapour-diffusion method. Diffraction data were collected to 3.6 Å resolution using synchrotron radiation. The crystals...

Drosophila Longevity Assurance Conferred by Reduced Insulin Receptor Substrate Chico Partially Requires d4eBP.

Directory of Open Access Journals (Sweden)

Hua Bai

Full Text Available Mutations of the insulin/IGF signaling (IIS pathway extend Drosophila lifespan. Based on genetic epistasis analyses, this longevity assurance is attributed to downstream effects of the FOXO transcription factor. However, as reported FOXO accounts for only a portion of the observed longevity benefit, suggesting there are additional outputs of IIS to mediate aging. One candidate is target of rapamycin complex 1 (TORC1. Reduced TORC1 activity is reported to slow aging, whereas reduced IIS is reported to repress TORC1 activity. The eukaryotic translation initiation factor 4E binding protein (4E-BP is repressed by TORC1, and activated 4E-BP is reported to increase Drosophila lifespan. Here we use genetic epistasis analyses to test whether longevity assurance mutants of chico, the Drosophila insulin receptor substrate homolog, require Drosophila d4eBP to slow aging. In chico heterozygotes, which are robustly long-lived, d4eBP is required but not sufficient to slow aging. Remarkably, d4eBP is not required or sufficient for chico homozygotes to extend longevity. Likewise, chico heterozygote females partially require d4eBP to preserve age-dependent locomotion, and both chico genotypes require d4eBP to improve stress-resistance. Reproduction and most measures of growth affected by either chico genotype are always independent of d4eBP. In females, chico heterozygotes paradoxically produce more rather than less phosphorylated 4E-BP (p4E-BP. Altered IRS function within the IIS pathway of Drosophila appears to have partial, conditional capacity to regulate aging through an unconventional interaction with 4E-BP.

Effects of interleukin-1 receptor antagonist (IL-1Ra) gene 86 bp VNTR polymorphism on recurrent pregnancy loss: a case-control study.

Science.gov (United States)

Hajizadeh, Yasamin Sayed; Emami, Elina; Nottagh, Marina; Amini, Zahra; Maroufi, Nazila Fathi; Azimian, Saba Haj; Isazadeh, Alireza

2017-05-26

Objective Recurrent pregnancy loss (RPL) is a heterogeneous disease which is defined as two or more consecutive fetal losses during early pregnancy. Interleukin-1 receptor antagonist (IL-1Ra) is a anti-inflammatory cytokine, which inhibits IL-1 activity by binding to its receptors. The aim of this study was to investigate the association between RPL and IL-1Ra intron 2 polymorphism (86 bp VNTR) in Iranian women. Materials and methods In this case control study, genetic polymorphism was studied in 140 RPL patients and 140 healthy women as controls. Genomic DNA was extracted from the blood samples and polymorphism analysis was performed using the polymerase chain reaction (PCR) method. Finally, the data obtained were analyzed by statistical software. Results We found an increased frequency of the IL-1Ra 1/1 genotype in the case group compared to the control group. Whereas, the frequency of IL-1Ra genotype 1/2 was higher in control group than in the case group. However, we did not observe an association between IL-1Ra 86 bp VNTR polymorphism in intron 2 and RPL patients (p > 0.05). Conclusion IL-1Ra VNTR polymorphism may not be a genetic factor for RPL. However, investigation of IL-1Ra polymorphism was recommended in other populations and patients with recurrent pregnancy loss.

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

Multivalent display of the antimicrobial peptides BP100 and BP143

Directory of Open Access Journals (Sweden)

Imma Güell

2012-12-01

Full Text Available Carbohydrates are considered as promising templates for the display of multiple copies of antimicrobial peptides. Herein, we describe the design and synthesis of chimeric structures containing two or four copies of the antimicrobial peptides KKLFKKILKYL-NH2 (BP100 and KKLfKKILKYL-NH2 (BP143 attached to the carbohydrate template cyclodithioerythritol (cDTE or α-D-galactopyranoside (Galp. The synthesis involved the preparation of the corresponding peptide aldehyde followed by coupling to an aminooxy-functionalized carbohydrate template. After purification, the multivalent display systems were obtained in high purities (90–98% and in good yields (42–64%. These compounds were tested against plant and human pathogenic bacteria and screened for their cytotoxicity on eukaryotic cells. They showed lower MIC values than the parent peptides against the bacteria analyzed. In particular, the carbopeptides derived from cDTE and Galp, which contained two or four copies of BP100, respectively, were 2- to 8-fold more active than the monomeric peptide against the phytopathogenic bacteria. These results suggest that preassembling antimicrobial peptides to multimeric structures is not always associated with a significant improvement of the activity. In contrast, the carbopeptides synthesized were active against human red blood cells pointing out that peptide preassembly is critical for the hemolytic activity. Notably, peptide preassembly resulted in an enhanced bactericidal effect.

EST Table: BP182610 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP182610 NRPG0829 10/09/28 35 %/122 aa ref|XP_967620.1| PREDICTED: similar to anopheles stephen...nl|Amel|GB19565-PA 10/09/10 35 %/122 aa gi|91093471|ref|XP_967620.1| PREDICTED: similar to anopheles stephensi ubiquitin, putative [Tribolium castaneum] FS914988 NRPG ...

The fission yeast minichromosome maintenance (MCM)-binding protein (MCM-BP), Mcb1, regulates MCM function during prereplicative complex formation in DNA replication.

Science.gov (United States)

Santosa, Venny; Martha, Sabrina; Hirose, Noriaki; Tanaka, Katsunori

2013-03-08

The minichromosome maintenance (MCM) complex is a replicative helicase, which is essential for chromosome DNA replication. In recent years, the identification of a novel MCM-binding protein (MCM-BP) in most eukaryotes has led to numerous studies investigating its function and its relationship to the MCM complex. However, the mechanisms by which MCM-BP functions and associates with MCM complexes are not well understood; in addition, the functional role of MCM-BP remains controversial and may vary between model organisms. The present study aims to elucidate the nature and biological function of the MCM-BP ortholog, Mcb1, in fission yeast. The Mcb1 protein continuously interacts with MCM proteins during the cell cycle in vivo and can interact with any individual MCM subunit in vitro. To understand the detailed characteristics of mcb1(+), two temperature-sensitive mcb1 gene mutants (mcb1(ts)) were isolated. Extensive genetic analysis showed that the mcb1(ts) mutants were suppressed by a mcm5(+) multicopy plasmid and displayed synthetic defects with many S-phase-related gene mutants. Moreover, cyclin-dependent kinase modulation by Cig2 repression or Rum1 overproduction suppressed the mcb1(ts) mutants, suggesting the involvement of Mcb1 in pre-RC formation during DNA replication. These data are consistent with the observation that Mcm7 loading onto replication origins is reduced and S-phase progression is delayed in mcb1(ts) mutants. Furthermore, the mcb1(ts) mutation led to the redistribution of MCM subunits to the cytoplasm, and this redistribution was dependent on an active nuclear export system. These results strongly suggest that Mcb1 promotes efficient pre-RC formation during DNA replication by regulating the MCM complex.

The Fission Yeast Minichromosome Maintenance (MCM)-binding Protein (MCM-BP), Mcb1, Regulates MCM Function during Prereplicative Complex Formation in DNA Replication*

Science.gov (United States)

Santosa, Venny; Martha, Sabrina; Hirose, Noriaki; Tanaka, Katsunori

2013-01-01

The minichromosome maintenance (MCM) complex is a replicative helicase, which is essential for chromosome DNA replication. In recent years, the identification of a novel MCM-binding protein (MCM-BP) in most eukaryotes has led to numerous studies investigating its function and its relationship to the MCM complex. However, the mechanisms by which MCM-BP functions and associates with MCM complexes are not well understood; in addition, the functional role of MCM-BP remains controversial and may vary between model organisms. The present study aims to elucidate the nature and biological function of the MCM-BP ortholog, Mcb1, in fission yeast. The Mcb1 protein continuously interacts with MCM proteins during the cell cycle in vivo and can interact with any individual MCM subunit in vitro. To understand the detailed characteristics of mcb1+, two temperature-sensitive mcb1 gene mutants (mcb1ts) were isolated. Extensive genetic analysis showed that the mcb1ts mutants were suppressed by a mcm5+ multicopy plasmid and displayed synthetic defects with many S-phase-related gene mutants. Moreover, cyclin-dependent kinase modulation by Cig2 repression or Rum1 overproduction suppressed the mcb1ts mutants, suggesting the involvement of Mcb1 in pre-RC formation during DNA replication. These data are consistent with the observation that Mcm7 loading onto replication origins is reduced and S-phase progression is delayed in mcb1ts mutants. Furthermore, the mcb1ts mutation led to the redistribution of MCM subunits to the cytoplasm, and this redistribution was dependent on an active nuclear export system. These results strongly suggest that Mcb1 promotes efficient pre-RC formation during DNA replication by regulating the MCM complex. PMID:23322785

EST Table: BP121050 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP121050 ceN-4078 10/09/28 35 %/122 aa ref|XP_967620.1| PREDICTED: similar to anopheles stephen...nl|Amel|GB19565-PA 10/09/10 35 %/122 aa gi|91093471|ref|XP_967620.1| PREDICTED: similar to anopheles stephensi ubiquitin, putative [Tribolium castaneum] FS914988 ceN- ...

Overexpressed CacyBP/SIP leads to the suppression of growth in renal cell carcinoma

International Nuclear Information System (INIS)

Sun, Shiren; Ning, Xiaoxuan; Liu, Jie; Liu, Lili; Chen, Yu; Han, Shuang; Zhang, Yanqi; Liang, Jie; Wu, Kaichun; Fan, Daiming

2007-01-01

Calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP), a target protein of S100, has been identified as a component of a novel ubiquitinylation complex leading to β-catenin degradation, which was found to be related to the malignant phenotypes of gastric cancer. However, the roles of CacyBP/SIP in renal cell carcinoma still remain unclear. In the present study, we had analyzed the expression of the CacyBP/SIP protein in human renal cancer cells and clinical tissue samples. The possible roles of CacyBP/SIP in regulating the malignant phenotype of renal cancer cells were also investigated. The results demonstrated that the expression of CacyBP/SIP was markedly down-regulated in renal cell carcinoma tissues and cell lines. Ectopic overexpression of CacyBP/SIP in A498 cells inhibited the proliferation of this cell and delayed cell cycle progression significantly, which might be related to the down-regulation of Cyclin D1 through reducing β-catenin protein. CacyBP/SIP also suppressed colony formation in soft agar and its tumorigenicity in nude mice. Taken together, our work showed that CacyBP/SIP, as a novel down-regulated gene in renal cell carcinoma, suppressed proliferation and tumorigenesis of renal cancer cells

BP report of the business year 1979

Energy Technology Data Exchange (ETDEWEB)

1980-01-01

The paper presents a survey about the development of the energy- and petroleum market during the year 1979. A commentary of the German BP A.G. and its activities is given here: personnel- and management policy, exploration, supply, refining and distribution, investigation, and development. After a survey about the business situation of the German BP A.G. the detailed annual balance sheets of 1979 of the German BP and of the whole enterprise are given.

200-BP-5 operable unit treatability test report

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-04-01

The 200-BP-5 Operable Unit was established in response to recommendations presented in the 200 East Groundwater Aggregate Area Management Study Report (AAMSR) (DOE-RL 1993a). Recognizing different approaches to remediation, the groundwater AAMSR recommended separating groundwater from source and vadose zone operable units and subdividing 200 East Area groundwater into two operable units. The division between the 200-BP-5 and 200-PO-1 Operable Units was based principally on source operable unit boundaries and distribution of groundwater plumes derived from either B Plant or Plutonium/Uranium Extraction (PUREX) Plant liquid waste disposal sites.

200-BP-5 operable unit treatability test report

International Nuclear Information System (INIS)

1996-04-01

The 200-BP-5 Operable Unit was established in response to recommendations presented in the 200 East Groundwater Aggregate Area Management Study Report (AAMSR) (DOE-RL 1993a). Recognizing different approaches to remediation, the groundwater AAMSR recommended separating groundwater from source and vadose zone operable units and subdividing 200 East Area groundwater into two operable units. The division between the 200-BP-5 and 200-PO-1 Operable Units was based principally on source operable unit boundaries and distribution of groundwater plumes derived from either B Plant or Plutonium/Uranium Extraction (PUREX) Plant liquid waste disposal sites

Face recognition based on improved BP neural network

Directory of Open Access Journals (Sweden)

Yue Gaili

2017-01-01

Full Text Available In order to improve the recognition rate of face recognition, face recognition algorithm based on histogram equalization, PCA and BP neural network is proposed. First, the face image is preprocessed by histogram equalization. Then, the classical PCA algorithm is used to extract the features of the histogram equalization image, and extract the principal component of the image. And then train the BP neural network using the trained training samples. This improved BP neural network weight adjustment method is used to train the network because the conventional BP algorithm has the disadvantages of slow convergence, easy to fall into local minima and training process. Finally, the BP neural network with the test sample input is trained to classify and identify the face images, and the recognition rate is obtained. Through the use of ORL database face image simulation experiment, the analysis results show that the improved BP neural network face recognition method can effectively improve the recognition rate of face recognition.

CRISPR/Cas9 mediated targeted mutagenesis of the fast growing cyanobacterium Synechococcus elongatus UTEX 2973.

Science.gov (United States)

Wendt, Kristen E; Ungerer, Justin; Cobb, Ryan E; Zhao, Huimin; Pakrasi, Himadri B

2016-06-23

As autotrophic prokaryotes, cyanobacteria are ideal chassis organisms for sustainable production of various useful compounds. The newly characterized cyanobacterium Synechococcus elongatus UTEX 2973 is a promising candidate for serving as a microbial cell factory because of its unusually rapid growth rate. Here, we seek to develop a genetic toolkit that enables extensive genomic engineering of Synechococcus 2973 by implementing a CRISPR/Cas9 editing system. We targeted the nblA gene because of its important role in biological response to nitrogen deprivation conditions. First, we determined that the Streptococcus pyogenes Cas9 enzyme is toxic in cyanobacteria, and conjugational transfer of stable, replicating constructs containing the cas9 gene resulted in lethality. However, after switching to a vector that permitted transient expression of the cas9 gene, we achieved markerless editing in 100 % of cyanobacterial exconjugants after the first patch. Moreover, we could readily cure the organisms of antibiotic resistance, resulting in a markerless deletion strain. High expression levels of the Cas9 protein in Synechococcus 2973 appear to be toxic and result in cell death. However, introduction of a CRISPR/Cas9 genome editing system on a plasmid backbone that leads to transient cas9 expression allowed for efficient markerless genome editing in a wild type genetic background.

Modelling Pseudocalanus elongatus stage-structured population dynamics embedded in a water column ecosystem model for the northern North Sea

Science.gov (United States)

Moll, Andreas; Stegert, Christoph

2007-01-01

This paper outlines an approach to couple a structured zooplankton population model with state variables for eggs, nauplii, two copepodites stages and adults adapted to Pseudocalanus elongatus into the complex marine ecosystem model ECOHAM2 with 13 state variables resolving the carbon and nitrogen cycle. Different temperature and food scenarios derived from laboratory culture studies were examined to improve the process parameterisation for copepod stage dependent development processes. To study annual cycles under realistic weather and hydrographic conditions, the coupled ecosystem-zooplankton model is applied to a water column in the northern North Sea. The main ecosystem state variables were validated against observed monthly mean values. Then vertical profiles of selected state variables were compared to the physical forcing to study differences between zooplankton as one biomass state variable or partitioned into five population state variables. Simulated generation times are more affected by temperature than food conditions except during the spring phytoplankton bloom. Up to six generations within the annual cycle can be discerned in the simulation.

5-bp Classical Satellite DNA Loci from Chromosome-1 Instability in Cervical Neoplasia Detected by DNA Breakage Detection/Fluorescence in Situ Hybridization (DBD-FISH

Directory of Open Access Journals (Sweden)

Jaime Gosálvez

2013-02-01

Full Text Available We aimed to evaluate the association between the progressive stages of cervical neoplasia and DNA damage in 5-bp classical satellite DNA sequences from chromosome-1 in cervical epithelium and in peripheral blood lymphocytes using DNA breakage detection/fluorescence in situ hybridization (DBD-FISH. A hospital-based unmatched case-control study was conducted in 2011 with a sample of 30 women grouped according to disease stage and selected according to histological diagnosis; 10 with low-grade squamous intraepithelial lesions (LG-SIL, 10 with high-grade SIL (HG-SIL, and 10 with no cervical lesions, from the Unidad Medica de Alta Especialidad of The Mexican Social Security Institute, IMSS, Mexico. Specific chromosome damage levels in 5-bp classical satellite DNA sequences from chromosome-1 were evaluated in cervical epithelium and peripheral blood lymphocytes using the DBD-FISH technique. Whole-genome DNA hybridization was used as a reference for the level of damage. Results of Kruskal-Wallis test showed a significant increase according to neoplastic development in both tissues. The instability of 5-bp classical satellite DNA sequences from chromosome-1 was evidenced using chromosome-orientation FISH. In conclusion, we suggest that the progression to malignant transformation involves an increase in the instability of 5-bp classical satellite DNA sequences from chromosome-1.

5-bp Classical Satellite DNA Loci from Chromosome-1 Instability in Cervical Neoplasia Detected by DNA Breakage Detection/Fluorescence in Situ Hybridization (DBD-FISH).

Science.gov (United States)

Cortés-Gutiérrez, Elva I; Ortíz-Hernández, Brenda L; Dávila-Rodríguez, Martha I; Cerda-Flores, Ricardo M; Fernández, José Luis; López-Fernández, Carmen; Gosálvez, Jaime

2013-02-19

We aimed to evaluate the association between the progressive stages of cervical neoplasia and DNA damage in 5-bp classical satellite DNA sequences from chromosome-1 in cervical epithelium and in peripheral blood lymphocytes using DNA breakage detection/fluorescence in situ hybridization (DBD-FISH). A hospital-based unmatched case-control study was conducted in 2011 with a sample of 30 women grouped according to disease stage and selected according to histological diagnosis; 10 with low-grade squamous intraepithelial lesions (LG-SIL), 10 with high-grade SIL (HG-SIL), and 10 with no cervical lesions, from the Unidad Medica de Alta Especialidad of The Mexican Social Security Institute, IMSS, Mexico. Specific chromosome damage levels in 5-bp classical satellite DNA sequences from chromosome-1 were evaluated in cervical epithelium and peripheral blood lymphocytes using the DBD-FISH technique. Whole-genome DNA hybridization was used as a reference for the level of damage. Results of Kruskal-Wallis test showed a significant increase according to neoplastic development in both tissues. The instability of 5-bp classical satellite DNA sequences from chromosome-1 was evidenced using chromosome-orientation FISH. In conclusion, we suggest that the progression to malignant transformation involves an increase in the instability of 5-bp classical satellite DNA sequences from chromosome-1.

BP Canada Energy Company : climate change action plan update 1999-2000

International Nuclear Information System (INIS)

2001-10-01

An aggressive, world-wide target for a 10 per cent reduction of greenhouse gas emissions was set by BP p.l.c. and BP Canada Energy Company has supported this endeavour. Six major areas have been identified as offering potential solutions to the problem of climate change: the control of greenhouse gases, the conservation of energy, the introduction of new technologies, the promotion of flexible market instruments, the participation in the policy process, and an investment in research. This document reviewed the efforts expanded to date in those areas. It was noted that a deliberate shift was made by BP leadership from oil to natural gas production, releasing much less carbon dioxide in the atmosphere when burned. A brief overview of the operations of BP Canada Energy Company was provided in chapter 1, followed by the philosophy concerning greenhouse gases in chapter 2. In chapter 3, the topic of BP's global emissions trading system was discussed. The current and projected greenhouse gas emissions were looked at in chapter 4, while chapter 5 dealt with setting global targets, with specific emphasis on Canadian targets. In chapter 6 , the emphasis was placed on BP's emission reduction initiatives. In chapter 7, the question of raising awareness was examined. 7 tabs., 7 figs

COPS5 (Jab1) protein increases β site processing of amyloid precursor protein and amyloid β peptide generation by stabilizing RanBP9 protein levels.

Science.gov (United States)

Wang, Hongjie; Dey, Debleena; Carrera, Ivan; Minond, Dmitriy; Bianchi, Elisabetta; Xu, Shaohua; Lakshmana, Madepalli K

2013-09-13

Increased processing of amyloid precursor protein (APP) and accumulation of neurotoxic amyloid β peptide (Aβ) in the brain is central to the pathogenesis of Alzheimer's disease (AD). Therefore, the identification of molecules that regulate Aβ generation is crucial for future therapeutic approaches for AD. We demonstrated previously that RanBP9 regulates Aβ generation in a number of cell lines and primary neuronal cultures by forming tripartite protein complexes with APP, low-density lipoprotein-related protein, and BACE1, consequently leading to increased amyloid plaque burden in the brain. RanBP9 is a scaffold protein that exists and functions in multiprotein complexes. To identify other proteins that may bind RanBP9 and regulate Aβ levels, we used a two-hybrid analysis against a human brain cDNA library and identified COPS5 as a novel RanBP9-interacting protein. This interaction was confirmed by coimmunoprecipitation experiments in both neuronal and non-neuronal cells and mouse brain. Colocalization of COPS5 and RanBP9 in the same subcellular compartments further supported the interaction of both proteins. Furthermore, like RanBP9, COPS5 robustly increased Aβ generation, followed by increased soluble APP-β (sAPP-β) and decreased soluble-APP-α (sAPP-α) levels. Most importantly, down-regulation of COPS5 by siRNAs reduced Aβ generation, implying that endogenous COPS5 regulates Aβ generation. Finally, COPS5 levels were increased significantly in AD brains and APΔE9 transgenic mice, and overexpression of COPS5 strongly increased RanBP9 protein levels by increasing its half-life. Taken together, these results suggest that COPS5 increases Aβ generation by increasing RanBP9 levels. Thus, COPS5 is a novel RanBP9-binding protein that increases APP processing and Aβ generation by stabilizing RanBP9 protein levels.

EST Table: BP182659 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP182659 NRPG0886 10/09/28 51 %/153 aa ref|XP_001659582.1| xaa-pro dipeptidase pepd/pepq(e.coli...) [Aedes aegypti] gb|EAT39285.1| xaa-pro dipeptidase pepd/pepq(e.coli) [Aedes aegypti] 10/08/29 ...33738|ref|XP_971576.2| PREDICTED: similar to xaa-pro dipeptidase pepd/pepq(e.coli) [Tribolium castaneum] FS768084 NRPG ...

EST Table: BP182152 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP182152 NRPG0186 10/09/28 87 %/125 aa ref|NP_001098702.1| nanos-like protein [Bomb...yx mori] gb|ABS17681.1| nanos-like protein [Bombyx mori] 10/08/29 low homology 10/08/28 n.h 10/09/10 low homology 10/09/10 low homology 10/09/10 low homology NM_001105232 NRPG ...

Bursopentin (BP5 protects dendritic cells from lipopolysaccharide-induced oxidative stress for immunosuppression.

Directory of Open Access Journals (Sweden)

Tao Qin

Full Text Available Dendritic cells (DCs play a vital role in the regulation of immune-mediated inflammatory diseases. Thus, DCs have been regarded as a major target for the development of immunomodulators. However, oxidative stress could disturb inflammatory regulation in DCs. Here, we examined the effect of bursopentine (BP5, a novel pentapeptide isolated from chicken bursa of fabricius, on the protection of DCs against oxidative stress for immunosuppression. BP5 showed potent protective effects against the lipopolysaccharide (LPS-induced oxidative stress in DCs, including nitric oxide, reactive oxygen species and lipid peroxidation. Furthermore, BP5 elevated the level of cellular reductive status through increasing the reduced glutathione (GSH and the GSH/GSSG ratio. Concomitant with these, the activities of several antioxidative redox enzymes, including glutathione peroxidase (GPx, catalase (CAT and superoxide dismutase (SOD, were obviously enhanced. BP5 also suppressed submucosal DC maturation in the LPS-stimulated intestinal epithelial cells (ECs/DCs coculture system. Finally, we found that heme oxygenase 1 (HO-1 was remarkably upregulated by BP5 in the LPS-induced DCs, and played an important role in the suppression of oxidative stress and DC maturation. These results suggested that BP5 could protect the LPS-activated DCs against oxidative stress and have potential applications in DC-related inflammatory responses.

Effect of 2,4-dihydroxybenzophenone (BP1) on early life-stage development of the marine copepod Acartia tonsa at different temperatures and salinities

DEFF Research Database (Denmark)

Kusk, Kresten Ole; Avdolli, Manola; Wollenberger, Leah

2011-01-01

a copepodite stage (DT(½) ) at the different conditions were calculated. The DT(½) values decreased from 296 h at 15°C to 89 h at 25°C and were also affected by salinity (126 h at 15‰ and 167 h at 30‰), whereas the light:dark regime and culture density influenced development only to a minor extent. BP1......Benzophenone (BP)-type ultraviolet (UV) filters are widely used in cosmetic and sunscreen products and can enter the aquatic environment. Therefore, we investigated the subchronic toxicity of 2,4-dihydroxybenzophenone (BP1) on the marine calanoid copepod Acartia tonsa in an early life......-stage development study. Since developmental endpoints depend on environmental conditions, a preceding study of A. tonsa development was performed at three temperatures, four salinities, four light:dark regimes, six food densities, and four culture densities. Times elapsed until 50% of the population had reached...

Study on MPGA-BP of Gravity Dam Deformation Prediction

Directory of Open Access Journals (Sweden)

Xiaoyu Wang

2017-01-01

Full Text Available Displacement is an important physical quantity of hydraulic structures deformation monitoring, and its prediction accuracy is the premise of ensuring the safe operation. Most existing metaheuristic methods have three problems: (1 falling into local minimum easily, (2 slowing convergence, and (3 the initial value’s sensitivity. Resolving these three problems and improving the prediction accuracy necessitate the application of genetic algorithm-based backpropagation (GA-BP neural network and multiple population genetic algorithm (MPGA. A hybrid multiple population genetic algorithm backpropagation (MPGA-BP neural network algorithm is put forward to optimize deformation prediction from periodic monitoring surveys of hydraulic structures. This hybrid model is employed for analyzing the displacement of a gravity dam in China. The results show the proposed model is superior to an ordinary BP neural network and statistical regression model in the aspect of global search, convergence speed, and prediction accuracy.

Loss of PINK1 attenuates HIF-1α induction by preventing 4E-BP1-dependent switch in protein translation under hypoxia.

Science.gov (United States)

Lin, William; Wadlington, Natasha L; Chen, Linan; Zhuang, Xiaoxi; Brorson, James R; Kang, Un Jung

2014-02-19

Parkinson's disease (PD) has multiple proposed etiologies with implication of abnormalities in cellular homeostasis ranging from proteostasis to mitochondrial dynamics to energy metabolism. PINK1 mutations are associated with familial PD and here we discover a novel PINK1 mechanism in cellular stress response. Using hypoxia as a physiological trigger of oxidative stress and disruption in energy metabolism, we demonstrate that PINK1(-/-) mouse cells exhibited significantly reduced induction of HIF-1α protein, HIF-1α transcriptional activity, and hypoxia-responsive gene upregulation. Loss of PINK1 impairs both hypoxia-induced 4E-BP1 dephosphorylation and increase in the ratio of internal ribosomal entry site (IRES)-dependent to cap-dependent translation. These data suggest that PINK1 mediates adaptive responses by activating IRES-dependent translation, and the impairments in translation and the HIF-1α pathway may contribute to PINK1-associated PD pathogenesis that manifests under cellular stress.

EST Table: BP183868 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP183868 P5PG0462 10/09/28 50 %/126 aa ref|XP_001659582.1| xaa-pro dipeptidase pepd/pepq(e.coli...) [Aedes aegypti] gb|EAT39285.1| xaa-pro dipeptidase pepd/pepq(e.coli) [Aedes aegypti] 10/08/29 ...33738|ref|XP_971576.2| PREDICTED: similar to xaa-pro dipeptidase pepd/pepq(e.coli) [Tribolium castaneum] FS768084 P5PG ...

EST Table: BP126151 [KAIKOcDNA[Archive

Lifescience Database Archive (English)

Full Text Available BP126151 ps4M0084 10/09/28 52 %/232 aa ref|XP_001659582.1| xaa-pro dipeptidase pepd/pepq(e.coli...) [Aedes aegypti] gb|EAT39285.1| xaa-pro dipeptidase pepd/pepq(e.coli) [Aedes aegypti] 10/08/29 ...33738|ref|XP_971576.2| PREDICTED: similar to xaa-pro dipeptidase pepd/pepq(e.coli) [Tribolium castaneum] FS768084 ps4M ...

A 40-bp VNTR polymorphism in the 3'-untranslated region of DAT1/SLC6A3 is associated with ADHD but not with alcoholism.

Science.gov (United States)

Šerý, Omar; Paclt, Ivo; Drtílková, Ivana; Theiner, Pavel; Kopečková, Marta; Zvolský, Petr; Balcar, Vladimir J

2015-06-11

ADHD and alcoholism are psychiatric diseases with pathophysiology related to dopamine system. DAT1 belongs to the SLC6 family of transporters and is involved in the regulation of extracellular dopamine levels. A 40 bp variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region of DAT1/SLC6A3 gene was previously reported to be associated with various phenotypes involving disturbed regulation of dopaminergic neurotransmission. A total of 1312 subjects were included and genotyped for 40 bp VNTR polymorphism of DAT1/SLC6A3 gene in this study (441 alcoholics, 400 non-alcoholic controls, 218 ADHD children and 253 non ADHD children). Using miRBase software, we have performed a computer analysis of VNTR part of DAT1 gene for presence of miRNA binding sites. We have found significant relationships between ADHD and the 40 bp VNTR polymorphisms of DAT1/SLC6A3 gene (P VNTR polymorphism of DAT1/SLC6A3 gene has been detected. We have found an association between 40 bp VNTR polymorphism of DAT1/SLC6A3 gene and ADHD in the Czech population; in a broad agreement with studies in other population samples. Furthermore, we detected rare genotypes 8/10, 7/10 and 10/11 present in ADHD boys only and identified miRNAs that should be looked at as potential novel targets in the research on ADHD.

miR-644a Inhibits Cellular Proliferation and Invasion via Suppression of CtBP1 in Gastric Cancer Cells.

Science.gov (United States)

Li, Yingchao; Yan, Xiaoni; Ren, Li; Li, Yang

2018-01-19

Epithelial-mesenchymal transition (EMT) is one of the most important mechanisms in the metastasis of various cancers, including gastric cancer (GC). In this study, we explored the putative significance of miR-644a and its role in EMT-mediated metastasis of GC. We first detected the expression of miR-644a in a cohort of 107 GC tissues using quantitative RT-PCR. The expression of miR-644a was suppressed in GC tissues and was associated with a later clinical stage and tumor metastasis. Restoring the expression of miR-644a could significantly suppress the migration and invasion of HGC-27 and SGC-7901 cells, which might be correlated to its suppressive effect on the EMT process. We also found that carboxyl-terminal-binding protein 1 (CtBP1) was a putative target gene of miR-644a in GC and might be involved in the suppressive effect. Collectively, through targeting CtBP1-mediated suppression of the EMT process, miR-644a might suppress the tumor metastasis of GC cells.

Localized Movement and Levels of 53BP1 Protein Are Changed by gamma-irradiation in PML Deficient Cells

Czech Academy of Sciences Publication Activity Database

Legartová, Soňa; Sehnalová, Petra; Malyšková, B.; Kuntziger, T.; Collas, P.; Cmarko, D.; Raška, I.; Sorokin, D.V.; Kozubek, Stanislav; Bártová, Eva

2016-01-01

Roč. 117, č. 11 (2016), s. 2583-2596 ISSN 0730-2312 R&D Projects: GA ČR GBP302/12/G157; GA ČR GA13-07822S; GA MŠk 7F14369 Institutional support: RVO:68081707 Keywords : DNA REPAIR * 53BP1 PROTEIN * PML BODIES Subject RIV: BO - Biophysics Impact factor: 3.085, year: 2016

Detection of DNA Double Strand Breaks by γH2AX Does Not Result in 53bp1 Recruitment in Mouse Retinal Tissues

Directory of Open Access Journals (Sweden)

Brigitte Müller

2018-05-01

Full Text Available Gene editing is an attractive potential treatment of inherited retinopathies. However, it often relies on endogenous DNA repair. Retinal DNA repair is incompletely characterized in humans and animal models. We investigated recruitment of the double stranded break (DSB repair complex of γH2AX and 53bp1 in both developing and mature mouse neuroretinas. We evaluated the immunofluorescent retinal expression of these proteins during development (P07-P30 in normal and retinal degeneration models, as well as in potassium bromate induced DSB repair in normal adult (3 months retinal explants. The two murine retinopathy models used had different mutations in Pde6b: the severe rd1 and the milder rd10 models. Compared to normal adult retina, we found increased numbers of γH2AX positive foci in all retinal neurons of the developing retina in both model and control retinas, as well as in wild type untreated retinal explant cultures. In contrast, the 53bp1 staining of the retina differed both in amount and character between cell types at all ages and in all model systems. There was strong pan nuclear staining in ganglion, amacrine, and horizontal cells, and cone photoreceptors, which was attenuated. Rod photoreceptors did not stain unequivocally. In all samples, 53bp1 stained foci only rarely occurred. Co-localization of 53bp1 and γH2AX staining was a very rare event (< 1% of γH2AX foci in the ONL and < 3% in the INL, suggesting the potential for alternate DSB sensing and repair proteins in the murine retina. At a minimum, murine retinal DSB repair does not appear to follow canonical pathways, and our findings suggests further investigation is warranted.

200-BP-1 Prototype Hanford Barrier -- 15 Years of Performance Monitoring

Energy Technology Data Exchange (ETDEWEB)

Ward, Anderson L.; Draper, Kathryn E.; Link, Steven O.; Clayton, Ray E.

2011-09-30

Monitoring is an essential component of engineered barrier system design and operation. A composite capacitive cover, including a capillary break and an evapotranspiration (ET) barrier at the Hanford Site, is generating data that can be used to help resolve these issues. The prototype Hanford barrier was constructed over the 216-B-57 Crib in 1994 to evaluate surface-barrier constructability, construction costs, and physical and hydrologic performance at the field scale. The barrier has been routinely monitored between November 1994 and September 1998 as part of a Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA) treatability test of barrier performance for the 200 BP 1 Operable Unit. Since FY 1998, monitoring has focused on a more limited set of key water balance, stability, and biotic parameters. In FY 2009, data collection was focused on: (1) water-balance monitoring, consisting of precipitation, runoff, soil moisture storage, and drainage measurements with evapotranspiration calculated by difference; (2) stability monitoring, consisting of asphalt-layer-settlement, basalt-side-slope-stability, and surface-elevation measurements; (3) vegetation dynamics; and (4) animal use. September 2009 marked 15 years since the start of monitoring and the collection of performance data. This report describes the results of monitoring activities during the period October 1, 2008, through September 30, 2009, and summarizes the 15 years of performance data collected from September 1994 through September 2009.

A central role for R7bp in the regulation of itch sensation.

Science.gov (United States)

Pandey, Mritunjay; Zhang, Jian-Hua; Mishra, Santosh K; Adikaram, Poorni R; Harris, Benjamin; Kahler, John F; Loshakov, Anna; Sholevar, Roxanne; Genis, Allison; Kittock, Claire; Kabat, Juraj; Ganesan, Sundar; Neubig, Richard R; Hoon, Mark A; Simonds, William F

2017-05-01

Itch is a protective sensation producing a desire to scratch. Pathologic itch can be a chronic symptom of illnesses such as uremia, cholestatic liver disease, neuropathies and dermatitis, however current therapeutic options are limited. Many types of cell surface receptors, including those present on cells in the skin, on sensory neurons and on neurons in the spinal cord, have been implicated in itch signaling. The role of G protein signaling in the regulation of pruriception is poorly understood. We identify here 2 G protein signaling components whose mutation impairs itch sensation. R7bp (a.k.a. Rgs7bp) is a palmitoylated membrane anchoring protein expressed in neurons that facilitates Gαi/o -directed GTPase activating protein activity mediated by the Gβ5/R7-RGS complex. Knockout of R7bp diminishes scratching responses to multiple cutaneously applied and intrathecally-administered pruritogens in mice. Knock-in to mice of a GTPase activating protein-insensitive mutant of Gαo (Gnao1 G184S/+) produces a similar pruriceptive phenotype. The pruriceptive defect in R7bp knockout mice was rescued in double knockout mice also lacking Oprk1, encoding the G protein-coupled kappa-opioid receptor whose activation is known to inhibit itch sensation. In a model of atopic dermatitis (eczema), R7bp knockout mice showed diminished scratching behavior and enhanced sensitivity to kappa opioid agonists. Taken together, our results indicate that R7bp is a key regulator of itch sensation and suggest the potential targeting of R7bp-dependent GTPase activating protein activity as a novel therapeutic strategy for pathological itch.

DNA damage response mediators MDC1 and 53BP1: constitutive activation and aberrant loss in breast and lung cancer, but not in testicular germ cell tumours

Czech Academy of Sciences Publication Activity Database

Bartkova, J.; Hořejší, Zuzana; Sehested, M.; Nesland, J.M.; Rajpert-De Meyts, E.; Skakkebaek, N.E.; Stucki, M.; Jackson, S.; Lukas, J.; Bartek, Jiří

2007-01-01

Roč. 26, č. 53 (2007), s. 7414-7422 ISSN 0950-9232 Institutional research plan: CEZ:AV0Z50520514 Keywords : DNA damage response * cancer * MDC1 and 53BP1 defects * tumour suppressors Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.440, year: 2007

The prenyl-binding protein PrBP/δ: a chaperone participating in intracellular trafficking.

Science.gov (United States)

Zhang, Houbin; Constantine, Ryan; Frederick, Jeanne M; Baehr, Wolfgang

2012-12-15

Expressed ubiquitously, PrBP/δ functions as chaperone/co-factor in the transport of a subset of prenylated proteins. PrBP/δ features an immunoglobulin-like β-sandwich fold for lipid binding, and interacts with diverse partners. PrBP/δ binds both C-terminal C15 and C20 prenyl side chains of phototransduction polypeptides and small GTP-binding (G) proteins of the Ras superfamily. PrBP/δ also interacts with the small GTPases, ARL2 and ARL3, which act as release factors (GDFs) for prenylated cargo. Targeted deletion of the mouse Pde6d gene encoding PrBP/δ resulted in impeded trafficking to the outer segments of GRK1 and cone PDE6 which are predicted to be farnesylated and geranylgeranylated, respectively. Rod and cone transducin trafficking was largely unaffected. These trafficking defects produce progressive cone-rod dystrophy in the Pde6d(-/-) mouse. Copyright © 2012 Elsevier Ltd. All rights reserved.

Air Sampling Data for BP Spill/Deepwater Horizon

Data.gov (United States)

U.S. Environmental Protection Agency — The Deepwater Horizon oil spill (also referred to as the BP oil spill) began on 20 April 2010 in the Gulf of Mexico on the BP-operated Macondo Prospect. Following...

Waste Sampling Data for BP Spill/Deepwater Horizon

Data.gov (United States)

U.S. Environmental Protection Agency — The Deepwater Horizon oil spill (also referred to as the BP oil spill) began on 20 April 2010 in the Gulf of Mexico on the BP-operated Macondo Prospect. Following...

Air Monitoring Data for BP Spill/Deepwater Horizon

Data.gov (United States)

U.S. Environmental Protection Agency — The Deepwater Horizon oil spill (also referred to as the BP oil spill) began on 20 April 2010 in the Gulf of Mexico on the BP-operated Macondo Prospect. Following...

Water Sampling Data for BP Spill/Deepwater Horizon

Data.gov (United States)

U.S. Environmental Protection Agency — The Deepwater Horizon oil spill (also referred to as the BP oil spill) began on 20 April 2010 in the Gulf of Mexico on the BP-operated Macondo Prospect. Following...

Sediment Sampling Data for BP Spill/Deepwater Horizon

Data.gov (United States)

U.S. Environmental Protection Agency — The Deepwater Horizon oil spill (also referred to as the BP oil spill) began on 20 April 2010 in the Gulf of Mexico on the BP-operated Macondo Prospect. Following...

76 FR 69712 - Application To Export Electric Energy; BP Energy Company

Science.gov (United States)

2011-11-09

... DEPARTMENT OF ENERGY [OE Docket No. EA-315-A] Application To Export Electric Energy; BP Energy.... SUMMARY: BP Energy Company (BP Energy) has applied to renew its authority to transmit electric energy from... BP Energy to transmit electric energy from the United States to Canada as a power marketer for a five...

Nocturnal Hypertension and Altered Night-Day BP Profile and Atherosclerosis in Renal Transplant Patients.

Science.gov (United States)

Mallamaci, Francesca; Tripepi, Rocco; Leonardis, Daniela; Mafrica, Angela; Versace, Maria Carmela; Provenzano, Fabio; Tripepi, Giovanni; Zoccali, Carmine

2016-10-01

The clinical relevance of ambulatory blood pressure monitoring (ABPM) for risk stratification in renal transplant patients still remains poorly defined. We investigated the association between clinic and ABPM with an established biomarker of atherosclerosis (intima-media thickness [IMT] by echo-color Doppler) in a large, inclusive survey (n = 172) in renal transplant patients at a single institution. Forty-two patients (24%) were classified as hypertensive by ABPM criteria and 29 (17%) by clinic blood pressure (BP) criteria. Average daytime and nighttime BP was 126 ± 12/78 ± 9 mm Hg and 123 ± 13/74 ± 10 mm Hg, respectively. Forty-five patients (26%) were classified as hypertensive by the daytime criterion (>135/85 mm Hg) and a much higher proportion (n = 119, 69%) by the nighttime criterion (>120/70 mm Hg). Sixty-two patients (36%) had a night-day ratio of 1 or greater, indicating clear-cut nondipping. The average nighttime systolic BP (r = 0.24, P = 0.001) and the night-day systolic BP ratio (r = 0.23, P = 0.002) were directly related to IMT, and these associations were much more robust than the 24-hour systolic BP-IMT relationship (r = 0.16, P = 0.04). Average daytime BP and clinic B were unrelated to IMT. In a multiple regression analysis adjusting for confounders, the night-day systolic BP ratio maintained an independent association with IMT (β = 0.14, P = 0.04). In renal transplant patients, the prevalence of nocturnal hypertension by far exceeds the prevalence of hypertension as assessed by clinic, daytime, and 24-hour ABPM. Nighttime systolic BP and the night-day ratio but no other BP metrics are independently associated with IMT. Blood pressure during nighttime may provide unique information for the assessment of cardiovascular risk attributable to BP burden in renal transplant patients.

Note: Primer Amysat 001; Fragment size is 211bp

Indian Academy of Sciences (India)

Renuka

Bhandara : Lanes 1–14 represent different strains of Bhandara Ecorace. Note: Primer Amysat 001; Fragment size is 211bp. Fig. 1. SSR profiles generated from genomic DNA of 16 strains from different individuals of (A.L, D. TV, D. BV, Modal, Sukinda, Raily, Bhandara) ecoraces of tasar silk worm, Antheraea mylitta using the.

Tyrosine phosphorylation of 3BP2 is indispensable for the interaction with VAV3 in chicken DT40 cells

Energy Technology Data Exchange (ETDEWEB)

Chihara, Kazuyasu [Division of Genome Science and Microbiology, Department of Pathological Sciences, Faculty of Medical Sciences, Fukui 910-1193 (Japan); Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193 (Japan); Kimura, Yukihiro [Division of Genome Science and Microbiology, Department of Pathological Sciences, Faculty of Medical Sciences, Fukui 910-1193 (Japan); Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Sciences, Fukui 910-1193 (Japan); Honjoh, Chisato [Division of Genome Science and Microbiology, Department of Pathological Sciences, Faculty of Medical Sciences, Fukui 910-1193 (Japan); Third Department of Internal Medicine, Faculty of Medical Sciences, Fukui 910-1193 (Japan); Yamauchi, Shota; Takeuchi, Kenji [Division of Genome Science and Microbiology, Department of Pathological Sciences, Faculty of Medical Sciences, Fukui 910-1193 (Japan); Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193 (Japan); Sada, Kiyonao, E-mail: ksada@u-fukui.ac.jp [Division of Genome Science and Microbiology, Department of Pathological Sciences, Faculty of Medical Sciences, Fukui 910-1193 (Japan); Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193 (Japan)

2014-03-10

Adaptor protein c-Abl SH3 domain-binding protein-2 (3BP2) is known to play regulatory roles in immunoreceptor-mediated signal transduction. We have previously demonstrated that Tyr{sup 174}, Tyr{sup 183} and Tyr{sup 446} in mouse 3BP2 are predominantly phosphorylated by Syk, and the phosphorylation of Tyr{sup 183} and the Src homology 2 (SH2) domain of mouse 3BP2 are critical for B cell receptor (BCR)-induced activation of nuclear factor of activated T cells (NFAT) in human B cells. In this report, we have shown that Syk, but not Abl family protein-tyrosine kinases, is critical for BCR-mediated tyrosine phosphorylation of 3BP2 in chicken DT40 cells. Mutational analysis showed that Tyr{sup 174}, Tyr{sup 183} and Tyr{sup 426} of chicken 3BP2 are the major phosphorylation sites by Syk and the SH2 domain of 3BP2 is critical for tyrosine phosphorylation. In addition, phosphorylation of Tyr{sup 426} is required for the inducible interaction with the SH2 domain of Vav3. Moreover, the expression of the mutant form of 3BP2 in which Tyr{sup 426} was substituted to Phe resulted in the reduction in BCR-mediated Rac1 activation, when compared with the case of wild-type. Altogether, these data suggest that 3BP2 is involved in the activation of Rac1 through the regulation of Vav3 by Syk-dependent phosphorylation of Tyr{sup 426} following BCR stimulation. - Highlights: • 3BP2 is phosphorylated by Syk, but not Abl family kinases in BCR signaling. • Tyr183 and Tyr426 in chicken 3BP2 are the major phosphorylation sites by Syk. • The SH2 domain of 3BP2 is critical for tyrosine phosphorylation of 3BP2. • Phosphorylation of Tyr426 in 3BP2 is required for the inducible binding with Vav3. • 3BP2 is involved in the regulation of BCR-mediated Rac1 activation.

Tyrosine phosphorylation of 3BP2 is indispensable for the interaction with VAV3 in chicken DT40 cells

International Nuclear Information System (INIS)

Chihara, Kazuyasu; Kimura, Yukihiro; Honjoh, Chisato; Yamauchi, Shota; Takeuchi, Kenji; Sada, Kiyonao

2014-01-01

Adaptor protein c-Abl SH3 domain-binding protein-2 (3BP2) is known to play regulatory roles in immunoreceptor-mediated signal transduction. We have previously demonstrated that Tyr 174 , Tyr 183 and Tyr 446 in mouse 3BP2 are predominantly phosphorylated by Syk, and the phosphorylation of Tyr 183 and the Src homology 2 (SH2) domain of mouse 3BP2 are critical for B cell receptor (BCR)-induced activation of nuclear factor of activated T cells (NFAT) in human B cells. In this report, we have shown that Syk, but not Abl family protein-tyrosine kinases, is critical for BCR-mediated tyrosine phosphorylation of 3BP2 in chicken DT40 cells. Mutational analysis showed that Tyr 174 , Tyr 183 and Tyr 426 of chicken 3BP2 are the major phosphorylation sites by Syk and the SH2 domain of 3BP2 is critical for tyrosine phosphorylation. In addition, phosphorylation of Tyr 426 is required for the inducible interaction with the SH2 domain of Vav3. Moreover, the expression of the mutant form of 3BP2 in which Tyr 426 was substituted to Phe resulted in the reduction in BCR-mediated Rac1 activation, when compared with the case of wild-type. Altogether, these data suggest that 3BP2 is involved in the activation of Rac1 through the regulation of Vav3 by Syk-dependent phosphorylation of Tyr 426 following BCR stimulation. - Highlights: • 3BP2 is phosphorylated by Syk, but not Abl family kinases in BCR signaling. • Tyr183 and Tyr426 in chicken 3BP2 are the major phosphorylation sites by Syk. • The SH2 domain of 3BP2 is critical for tyrosine phosphorylation of 3BP2. • Phosphorylation of Tyr426 in 3BP2 is required for the inducible binding with Vav3. • 3BP2 is involved in the regulation of BCR-mediated Rac1 activation

Isolation, one-step affinity purification, and characterization of a polyextremotolerant laccase from the halophilic bacterium Aquisalibacillus elongatus and its application in the delignification of sugar beet pulp.

Science.gov (United States)

Rezaei, Shahla; Shahverdi, Ahmad Reza; Faramarzi, Mohammad Ali

2017-04-01

The aim of the present work was to study the ability of a halophilic bacterial laccase to efficient delignification in extreme conditions. Here, a highly stable extracellular laccase showing ligninolytic activity from halophilic Aquisalibacillus elongatus is described. The laccase production was strongly influenced by NaCl and CuSO 4 and under optimal conditions reached 4.8UmL -1 . The monomeric enzyme of 75kDa was purified by a synthetic affinity column with 68.2% yield and 99.8-fold purification. The enzyme showed some valuable features viz. stability against a wide range of organic solvents, salts, metals, inhibitors, and surfactants and specificity to a wide spectrum of substrates diverse in structure and redox potential. It retained more than 50% of the original activity at 25-75°C and pH 5.0-10.0. Furthermore, the enzyme was found to be effective in the delignification of sugar beet pulp in an ionic liquid that makes it useful for industrial applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

BP/Mobil. Joint-venture directions for use

International Nuclear Information System (INIS)

Anon.

1997-01-01

This paper analyzes the economical reasons which have led BP and Mobil companies to join their forces in 1996. Thanks to their complementarity and to their European implantation, the two companies could win the first or second position in petroleum products marketing in 8 European countries. The cumulated petrol sales and the number of petrol stations of the BP/Mobil joint venture are the highest in Europe (800 petrol stations in France). (J.S.)

IGF2BP2 alternative variants associated with glutamic acid decarboxylase antibodies negative diabetes in Malaysian subjects.

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Sameer D Salem

Full Text Available BACKGROUND: The association of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2 common variants (rs4402960 and rs1470579 with type 2 diabetes (T2D has been performed in different populations. The aim of this study was to evaluate the association of alternative variants of IGF2BP2; rs6777038, rs16860234 and rs7651090 with glutamic acid decarboxylase antibodies (GADA negative diabetes in Malaysian Subjects. METHODS/PRINCIPAL FINDINGS: IGF2BP2; rs6777038, rs16860234 and rs7651090 single nucleotide polymorphisms (SNPs were genotyped in 1107 GADA negative diabetic patients and 620 control subjects of Asian from Malaysia. The additive genetic model adjusted for age, race, gender and BMI showed that alternative variants; rs6777038, rs16860234 and rs7651090 of IGF2BP2 associated with GADA negative diabetes (OR = 1.21; 1.36; 1.35, P = 0.03; 0.0004; 0.0002, respectively. In addition, the CCG haplotype and diplotype CCG-TCG increased the risk of diabetes (OR = 1.51, P = 0.01; OR = 2.36, P = 0.009, respectively. CONCLUSIONS/SIGNIFICANCE: IGF2BP2 alternative variants were associated with GADA negative diabetes. The IGF2BP2 haplotypes and diplotypes increased the risk of diabetes in Malaysian subject.

Surface Water Sampling Data for BP Spill/Deepwater Horizon

Data.gov (United States)

U.S. Environmental Protection Agency — The Deepwater Horizon oil spill (also referred to as the BP oil spill) began on 20 April 2010 in the Gulf of Mexico on the BP-operated Macondo Prospect. Following...

Molecular modeling and computational simulation of the photosystem-II reaction center to address isoproturon resistance in Phalaris minor.

Science.gov (United States)

Singh, Durg Vijay; Agarwal, Shikha; Kesharwani, Rajesh Kumar; Misra, Krishna

2012-08-01

Isoproturon is the only herbicide that can control Phalaris minor, a competitive weed of wheat that developed resistance in 1992. Resistance against isoproturon was reported to be due to a mutation in the psbA gene that encodes the isoproturon-binding D1 protein. Previously in our laboratory, a triazole derivative of isoproturon (TDI) was synthesized and found to be active against both susceptible and resistant biotypes at 0.5 kg/ha but has shown poor specificity. In the present study, both susceptible D1((S)), resistant D1((R)) and D2 proteins of the PS-II reaction center of P. minor have been modeled and simulated, selecting the crystal structure of PS-II from Thermosynechococcus elongatus (2AXT.pdb) as template. Loop regions were refined, and the complete reaction center D1/D2 was simulated with GROMACS in lipid (1-palmitoyl-2-oleoylglycero-3-phosphoglycerol, POPG) environment along with ligands and cofactor. Both S and R models were energy minimized using steepest decent equilibrated with isotropic pressure coupling and temperature coupling using a Berendsen protocol, and subjected to 1,000 ps of MD simulation. As a result of MD simulation, the best model obtained in lipid environment had five chlorophylls, two plastoquinones, two phenophytins and a bicarbonate ion along with cofactor Fe and oxygen evolving center (OEC). The triazole derivative of isoproturon was used as lead molecule for docking. The best worked out conformation of TDI was chosen for receptor-based de novo ligand design. In silico designed molecules were screened and, as a result, only those molecules that show higher docking and binding energies in comparison to isoproturon and its triazole derivative were proposed for synthesis in order to get more potent, non-resistant and more selective TDI analogs.

NFκBP65 transcription factor modulates resistance to doxorubicin through ABC transporters in breast cancer.

Science.gov (United States)

Velaei, Kobra; Samadi, Nasser; Soltani, Sina; Barazvan, Balal; Soleimani Rad, Jafar

2017-07-01

Shedding light on chemoresistance biology of breast cancer could contribute to enhance the clinical outcome. Intrinsic or acquired resistance to chemotherapy is a major problem in breast cancer treatment. The NFκB pathway by siRNAP65 and JSH-23 as a translocational inhibitor of NFκBP65 in the doxorubicin-resistant MCF-7 (MCF-7/Dox) and MCF-7 cells was blocked. Then, the ABC transporter expression and function were assessed by real-time qRT-PCR and flow cytometry, respectively. Induction of apoptosis was evaluated after inhibition of the NFΚB pathway as well. Our study underlined the upregulation of NFκBP65 and anti-apoptotic Bcl-2 and downregulation of pro-apoptotic Bax in the MCF-7/Dox cells compared with control MCF-7 cells. Here, we showed that interplay between nuclear factor kappa B P65 (NFkBP65) as a transcriptional regulator and ABC transporters in the MCF-7/Dox cancer cells. We found that inhibition of the elevated expression of NFκBP65 in the resistant breast cancer, whether translocational inhibition or silencing by siRNA, decreased the expression and function of MDR1 and MRP1 efflux pumps. Furthermore, the blockade of NFκBP65 promoted apoptosis via modulating Bcl-2 and BAX expression. After inhibition of the NFκBP65 signaling pathway, elevated baseline expression of survival Bcl-2 gene in the resistant breast cells significantly decreased. Suppression of the NFκB pathway has a profound dual impact on promoting the intrinsic apoptotic pathway and reducing ABC transporter function and expression, which are some of the chemoresistance features. It was speculated that the NFκB pathway directly acts on doxorubicin-induced MDR1 and MRP1 expression in MCF-7/Dox cells.

4977-bp mitochondrial DNA deletion in infertile patients with varicocele.

Science.gov (United States)

Gashti, N G; Salehi, Z; Madani, A H; Dalivandan, S T

2014-04-01

Varicocele is the abnormal inflexion and distension of veins of the pampiniform plexus within spermatic cord and is one of the amendable causes of male infertility. It can increase reactive oxygen species (ROS) production in semen and cause oxidative stress. The purpose of this study was to analyse spermatozoa mtDNA 4977-bp deletion in infertile men with varicocele. To detect 4977-bp deletion in spermatozoa mtDNA, semen samples of 60 infertile patients with clinical varicocele and 90 normal men from northern Iran were prepared. After extraction of spermatozoa total DNA, Gap polymerase chain reaction (Gap PCR) was performed. 4977-bp deletion was observed in 81.66% of patients with varicocele, while approximately 15.55% of controls had this deletion. As spermatozoa from patients with varicocele had a high frequency of occurrence of 4977-bp deletion in mtDNA [OR = 24.18, 95% confidence interval (CI) = 10.15-57.57, P deletion in spermatozoa and cause infertility in north Iranian men. However, to determine the relation between sperm mtDNA 4977-bp deletion and varicocele-induced infertility, larger population-based studies are needed. It is concluded that there is an association between sperm mtDNA 4977-bp deletion and varicocele-induced infertility in the population studied. © 2013 Blackwell Verlag GmbH.

The MCM-associated protein MCM-BP is important for human nuclear morphology.

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Jagannathan, Madhav; Sakwe, Amos M; Nguyen, Tin; Frappier, Lori

2012-01-01

Mini-chromosome maintenance complex-binding protein (MCM-BP) was discovered as a protein that is strongly associated with human MCM proteins, known to be crucial for DNA replication in providing DNA helicase activity. The Xenopus MCM-BP homologue appears to play a role in unloading MCM complexes from chromatin after DNA synthesis; however, the importance of MCM-BP and its functional contribution to human cells has been unclear. Here we show that depletion of MCM-BP by sustained expression of short hairpin RNA (shRNA) results in highly abnormal nuclear morphology and centrosome amplification. The abnormal nuclear morphology was not seen with depletion of other MCM proteins and was rescued with shRNA-resistant MCM-BP. MCM-BP depletion was also found to result in transient activation of the G2 checkpoint, slowed progression through G2 and increased replication protein A foci, indicative of replication stress. In addition, MCM-BP depletion led to increased cellular levels of MCM proteins throughout the cell cycle including soluble MCM pools. The results suggest that MCM-BP makes multiple contributions to human cells that are not limited to unloading of the MCM complex.

76 FR 69713 - Application To Export Electric Energy; BP Energy Company

Science.gov (United States)

2011-11-09

... DEPARTMENT OF ENERGY [OE Docket No. EA-314-A] Application To Export Electric Energy; BP Energy.... SUMMARY: BP Energy Company (BP Energy) has applied to renew its authority to transmit electric energy from... electric energy from the United States to Mexico as a power marketer for a five-year term using existing...

Investigating the Role of the Arabidopsis Homologue of the Human G3BP in RNA Metabolism, Cellular Stress Responses and Innate Immunity

KAUST Repository

Abulfaraj, Aala A.

2018-04-01

Mitogen-activated protein kinases (MAPKs) belong to the most conserved signaling pathways and are found in all eukaryotes, including humans where they play important roles in various diseases and cancer. Stimulation of this signal transduction pathway by microbe-associated molecular patterns (MAMP) results in a multitude of events to regulate innate immune responses in Arabidopsis thaliana stimulating large-scale changes in gene expression. Starting from a phosphoproteomic screen in Arabidopsis thaliana wild type and mpk3, mpk4 and mpk6 mutants following microbe-associated molecular pattern (MAMP) treatment, several novel chromatin-associated proteins were identified that are differentially phosphorylated by stress-induced protein kinases. Arabidopsis Ras GTPase-activating protein SH3-domain-binding protein (AtG3BP-1) is a downstream putative substrate of the MAMP-stimulated MAPK pathway that is phosphorylated by MPK3, 4 and 6 in in vitro kinase assays. AtG3BP1 belongs to a highly conserved family of RNA-binding proteins in eukaryotes that link kinase receptormediated signaling to RNA metabolism. Here, we report the characterization of the Arabidopsis homolog of human G3BP1 in plant innate immunity. AtG3BP1 negatively regulates plant immunity and defense immune responses. Atg3bp1 mutant lines show constitutive stomata closure, expression of a number of key defense marker genes, and accumulate salicylic acid but not jasmonic acid. Furthermore, Atg3bp1 plants exhibit enhanced resistance to the biotrophic pathogen Pseudomonas syringae pv. tomato. Pathogen resistance was mediated by stomatal and apoplastic immunity in Atg3bp1. More generally, our data reinforce that AtG3BP1 is a key mediator of plant defense responses and transient expression of AtG3BP1 delivered striking disease resistance in the absence of yield penalty, highlighting a potential application of this gene in crop protection.

200-BP-11 operable unit and 216-B-3 main pond work/closure plan, Hanford Site, Richland, Washington. Volume 1: Field investigation and sampling strategy

International Nuclear Information System (INIS)

1994-09-01

This document coordinates a Resource Conservation and Recovery Act (RCRA) past-practice work plan for the 200-BP-11 Operable Unit and a RCRA closure/postclosure plan for the 216-B-3 Main Pond and 216-B-3-3 Ditch [treatment, storage, and/or disposal (TSD) unit]. Both RCRA TSD and past-practice waste management units are contained within the 200-BP-11 Operable Unit. The 200-BP-11 Operable Unit is a source operable unit located on the east side of the B Plant Source Aggregate Area in the 200 East Area of the Hanford Site. The operable unit lies just east of the 200 East Area perimeter fence and encompass approximately 476 hectares (1,175 acres). Source operable units include waste management units that are potential sources of radioactive and/or hazardous substance contamination. Source waste management units are categorized in the Hanford Federal Facility Agreement and Consent Order as either RCRA TSD, RCRA past-practice, or Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) past-practice. As listed below and in the Tri-Party Agreement, the 200-BP-11 Operable Unit contains five RCRA past-practice and five RCRA TSD waste management units. Additionally, for RCRA TSD permitting purposes, the RCRA TSD waste management units are subdivided into two RCRA TSD units

IGF2BP3 as a potential tissue marker for the diagnosis of esophageal high-grade intraepithelial neoplasia

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Zhang JJ

2017-08-01

Full Text Available Jingjing Zhang,1,* Qing Ji,2,* Chunhua Jiao,3,* Lihua Ren,4 Ye Zhao,4 Yanfang Chen,4 Ruihua Shi,4 Yadong Feng4 1State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 2Department of Emergency, Jingjiang People’s Hospital, Jingjiang, 3Department of Gastroenterology, First Affiliated Hospital with Nanjing Medical University, 4Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China *These authors contributed equally to this work Background: The clinical significance of insulin-like growth factor-II mRNA-binding protein-3 (IGF2BP3 in esophageal high-grade intraepithelial neoplasia (HGIN is not clear. This study was designed to characterize the expression of IGF2BP3 in HGIN. Patients and methods: IGF2BP3 expression was evaluated by Western blot analyses in 12 cases and by immunohistochemistry (IHC in 112 cases. The associations between IGF2BP3 expression in HGIN and the clinicopathological parameters were examined. Results: Moderate to strong IGF2BP3 expression was present in HGIN samples. Using IHC, it was found that IGF2BP3 was positive in 68 (60.71% cases. Intense IHC of IGF2BP3 in HGIN was associated with a deeper lesion depth, and the lesion depth was the only predictor of the positive expression of IGF2BP3. Conclusion: Our results suggested that IGF2BP3 may be a supplementary tissue marker for preoperative diagnosis of HGIN. Keywords: esophageal squamous cell carcinoma, precancerous lesion, immunohistochemistry detection, early diagnosis

Post glacial mass movements in Western Norway with special emphasis on the 2000 - 2200 BP and 2800 - 3200 BP periods - final report

International Nuclear Information System (INIS)

Boee, Reidulv; Lepland, Aivo; Blikra, Lars Harald; Longva, Oddvar; Soenstegaard, Eivind

2002-01-01

The Ormen Lange Gas Field was discovered in the Norwegian Sea outside the Moere og Romsdal in 1997. The development of this field which is located in the area of the Storegga Slide, requires safety assessment. The project aims to collect and compile data on slides, avalanches and gravitational faults that may have resulted from large earthquakes or tsunamis in the north west of Western Norway. A major task in the present project has been to investigate the spatial extent and interpret the origin of a postulated mass movement event ca. 2000 years ago and to evaluate its causes, climate variations, a tsunami (possibly caused by an earthquake affecting the offshore area), and earthquake only affecting parts of Western Norway or a combination of an earthquake and a tsunami. Several other mass movements, including the Storegga Slide tsunami deposits and pre-Storegga Slide slide and debris flow deposits have been studied both in the fjord and the lake sediments. Five of the 16 investigated fjords (Dalsfjorden, Foerdefjorden, Syvdsfjorden, Voldafjorden, Oerstadfjorden) provide evidence for a 2000 - 2200 years BP (calendar years before present, i.e. 1950) event. Previous investigations show no indication of a large shelf edge slide in the Storegga area, that may have created a tsunami at that time, nor are any mass movement deposits found on land or in the investigated lakes. This suggests that the 2000 - 2200 BP debris flows and turbidites were most likely related to one or more earthquakes on land or close to the coast and not an offshore mega slide generated tsunami. The Storegga Slide (8200 BP) tsunami deposits are observed in cores over most of the investigated area, both in the deep fjords and in lakes. Striking similarity between major slide and debris flow deposits at the 2000 - 2200 BP and ca. 11000 - 11700 BP stratigraphic levels suggest a common triggering mechanism, probably earthquakes with epicentres in the Sunnfjord Sunnmoere region. A period of debris flows

Gadolinium-enhanced cardiac MR exams of human subjects are associated with significant increases in the DNA repair marker 53BP1, but not the damage marker γH2AX.

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Jennifer S McDonald

Full Text Available Magnetic resonance imaging is considered low risk, yet recent studies have raised a concern of potential damage to DNA in peripheral blood leukocytes. This prospective Institutional Review Board-approved study examined potential double-strand DNA damage by analyzing changes in the DNA damage and repair markers γH2AX and 53BP1 in patients who underwent a 1.5 T gadolinium-enhanced cardiac magnetic resonance (MR exam. Sixty patients were enrolled (median age 55 years, 39 males. Patients with history of malignancy or who were receiving chemotherapy, radiation therapy, or steroids were excluded. MR sequence data were recorded and blood samples obtained immediately before and after MR exposure. An automated immunofluorescence assay quantified γH2AX or 53BP1 foci number in isolated peripheral blood mononuclear cells. Changes in foci number were analyzed using the Wilcoxon signed-rank test. Clinical and MR procedural characteristics were compared between patients who had a >10% increase in γH2AX or 53BP1 foci numbers and patients who did not. The number of γH2AX foci did not significantly change following cardiac MR (median foci per cell pre-MR = 0.11, post-MR = 0.11, p = .90, but the number of 53BP1 foci significantly increased following MR (median foci per cell pre-MR = 0.46, post-MR = 0.54, p = .0140. Clinical and MR characteristics did not differ significantly between patients who had at least a 10% increase in foci per cell and those who did not. We conclude that MR exposure leads to a small (median 25% increase in 53BP1 foci, however the clinical relevance of this increase is unknown and may be attributable to normal variation instead of MR exposure.

Bc→BP,BV Decays with the QCD Factorization Approach

International Nuclear Information System (INIS)

Chang, Qin; Wang, Na; Sun, Junfeng; Yang, Yueling

2015-01-01

We studied the nonleptonic B c →BP, BV decays with the QCD factorization approach. It is found that the Cabibbo favored processes of B c →B s π, B s ρ, B u K - are the promising decay channels with branching ratio larger than 1%, which should be observed earlier by the LHCb collaboration

Gear Fault Diagnosis Based on BP Neural Network

Science.gov (United States)

Huang, Yongsheng; Huang, Ruoshi

2018-03-01

Gear transmission is more complex, widely used in machinery fields, which form of fault has some nonlinear characteristics. This paper uses BP neural network to train the gear of four typical failure modes, and achieves satisfactory results. Tested by using test data, test results have an agreement with the actual results. The results show that the BP neural network can effectively solve the complex state of gear fault in the gear fault diagnosis.

Persistence of gamma-H2AX and 53BP1 foci in proliferating and nonproliferating human mammary epithelial cells after exposure to gamma-rays or iron ions

Energy Technology Data Exchange (ETDEWEB)

Groesser, Torsten; Chang, Hang; Fontenay, Gerald; Chen, James; Costes, Sylvain V.; Barcellos-Hoff, Mary Helen; Parvin, Bahram; Rydberg, Bjorn

2010-12-22

To investigate {gamma}-H2AX (phosphorylated histone H2AX) and 53BP1 (tumour protein 53 binding protein No. 1) foci formation and removal in proliferating and non-proliferating human mammary epithelial cells (HMEC) after exposure to sparsely and densely ionizing radiation under different cell culture conditions. HMEC cells were grown either as monolayers (2D) or in extracellular matrix to allow the formation of acinar structures in vitro (3D). Foci numbers were quantified by image analysis at various time points after exposure. Our results reveal that in non-proliferating cells under 2D and 3D cell culture conditions, iron-ion induced {gamma}-H2AX foci were still present at 72 h after exposure, although 53BP1 foci returned to control levels at 48 h. In contrast in proliferating HMEC, both {gamma}-H2AX and 53BP1 foci decreased to control levels during the 24-48 h time interval after irradiation under 2D conditions. Foci numbers decreased faster after {gamma}-ray irradiation and returned to control levels by 12 h regardless of marker, cell proliferation status, and cell culture condition. Conclusions: The disappearance of radiation induced {gamma}-H2AX and 53BP1 foci in HMEC have different dynamics that depend on radiation quality and proliferation status. Notably, the general patterns do not depend on the cell culture condition (2D versus 3D). We speculate that the persistent {gamma}-H2AX foci in iron-ion irradiated non-proliferating cells could be due to limited availability of double strand break (DSB) repair pathways in G0/G1-phase, or that repair of complex DSB requires replication or chromatin remodeling.

A new BP Fourier algorithm and its application in English teaching evaluation

Science.gov (United States)

Pei, Xuehui; Pei, Guixin

2017-08-01

BP neural network algorithm has wide adaptability and accuracy when used in complicated system evaluation, but its calculation defects such as slow convergence have limited its practical application. The paper tries to speed up the calculation convergence of BP neural network algorithm with Fourier basis functions and presents a new BP Fourier algorithm for complicated system evaluation. First, shortages and working principle of BP algorithm are analyzed for subsequent targeted improvement; Second, the presented BP Fourier algorithm adopts Fourier basis functions to simplify calculation structure, designs new calculation transfer function between input and output layers, and conducts theoretical analysis to prove the efficiency of the presented algorithm; Finally, the presented algorithm is used in evaluating university English teaching and the application results shows that the presented BP Fourier algorithm has better performance in calculation efficiency and evaluation accuracy and can be used in evaluating complicated system practically.

The human element of right-sizing. BP experiences

International Nuclear Information System (INIS)

Hollis, J.W.

1994-01-01

BP (British Petroleum) Exploration has been engaged in a world-wide repositioning exercise to improve its business performance. Despite a 40% fall in average oil price, the profitability and revenues have both grown, while the workforce has more than halved. BP is now able to test itself against price assumptions as low as $ 14 a barrel and make as good a return as it was near to $ 20. The paper discusses such a process of repositioning

The human element of right-sizing. BP experiences

Energy Technology Data Exchange (ETDEWEB)

Hollis, J W [BP Norge (Norway)

1994-12-31

BP (British Petroleum) Exploration has been engaged in a world-wide repositioning exercise to improve its business performance. Despite a 40% fall in average oil price, the profitability and revenues have both grown, while the workforce has more than halved. BP is now able to test itself against price assumptions as low as $ 14 a barrel and make as good a return as it was near to $ 20. The paper discusses such a process of repositioning

Construction and confirmation of the plasmid of human mitochondrial DNA 4977 bp deletion induced by ionizing radiation

International Nuclear Information System (INIS)

Chen Xiaosui; Zhou Lijun; Wang Yuxiao; Qu Jia; Feng Jiangbing; Lu Xue; Chen Deqing; Liu Qingjie

2006-01-01

Objective: To construct a stable plasmid that spanning deleted human mitochondrial DNA (mtDNA) 4977 bp induced by ionizing radiation and another one for control DNA fragment, in order to use in the human mitochondrial genome study in the future. Methods: The peripheral blood, which had no mtDNA 4977 bp deletion found in previous study, was exposed to 10 Gy 60 Co γ-rays in vitro. The total cell DNA was extracted and PCR was carried out: a nest-PCR of three-round PCR was used for the mtDNA 4977 bp deletion and one- round regular PCR was used for the control ND1 gene. The PCR products were used for transfection by electroporation and the positive clones were obtained after screening. The plasmid DNA was isolated and sequenced after enzymatic digestion and purification. The sequence result was BLASTed with the human mitochondrial genome. Results: The sizes of PCR products for the flanked 4977 bp deletion and the ND1 gene were similar with those predicted according to GeneBank. The sequences for the positive clones were above 99 per cent homologous with the human mitochondrial genome after BLASTed. Conclusion: The plasmids for deleted human mtDNA 4977 bp and control DNA fragment have been constructed successfully, and they could be used in the quality and quantity studies on human mtDNA 4977 bp deletion. (authors)

Stress-induced and cue-induced craving for alcohol in heavy drinkers: Preliminary evidence of genetic moderation by the OPRM1 and CRH-BP genes.

Science.gov (United States)

Ray, Lara A

2011-01-01

Neurobiological theories of addiction have highlighted disruption in stress pathways as a central feature of addictive disorders, and pharmacological treatments targeting stress mechanisms hold great promise. This study examines genetic determinants of stress-induced and cue-induced craving in heavy drinkers by testing single-nucleotide polymorphisms (SNPs) of the corticotrophin-releasing hormone binding protein (CRH-BP) gene and the mu-opioid receptor (OPRM1) gene. This study combines guided imagery stress exposure and in vivo alcohol cue exposure in a sample of 64 (23 women) non-treatment-seeking heavy drinkers. Analyses, uncorrected for multiple comparisons, revealed that a tag SNP of the CRH-BP gene (rs10055255) moderated stress-induced craving in this sample. The same SNP predicted greater affective responses to the stress manipulation, including greater levels of subjective tension and negative mood. The Asp40 allele of the OPRM1 was associated with greater cue-induced alcohol craving following the neutral imagery condition. These initial results extend recent preclinical and clinical findings implicating the CRH-BP in stress-related alcoholism and confirm the role of the Asp40 allele of the OPRM1 gene in reward-driven alcohol phenotypes. Human laboratory models of stress and cue-induced craving may be useful in pharmacotherapy development targeting dysregulation of stress systems. Larger studies are needed to validate these preliminary findings, which should also be extended to clinical samples. Copyright © 2010 by the Research Society on Alcoholism.

884 Cal.BP and all that

International Nuclear Information System (INIS)

Switsur, Roy

1986-01-01

A history of the development of the technique of radiocarbon dating highlights the two problems with this method. The first is calibration; the radiocarbon calendar is not linear. However two independent experiments to provide high precision measurements in tree rings have resulted in a high precision calibration curve. The second is how to denote radiocarbon ages and calibrated dates, as this depends on how the dendrochronology time scale used in the calibration is transferred to the actual calendar. If the zero of the dendroscale is transferred from the origin of the Christian calendar to AD 1950, radiocarbon ages are designated CAL BP (BP = before present). There is an alternative method which results in CAL AD and CAL BC. A suggestion for a standard notation is made to avoid the confusion of two systems. (U.K.)

BP teatas harvast edusammust / Hendrik Vosman

Index Scriptorium Estoniae

Vosman, Hendrik

2010-01-01

Naftakompanii BP teatas, et suudab Mehhiko lahest päevas kinni püüda sinna lekkinud 10 000 barrelit naftat. Tegu on ajutise lahendusega, lõplikult peaks naftavoo peatama merepõhja puuritavad nn. asenduskaevud

A New Open-framework Iron Borophosphate from Ionic Liquids: KFe[BP2O8(OH

Directory of Open Access Journals (Sweden)

Guangmei Wang

2011-04-01

Full Text Available A new open-framework iron borophosphate, KFe[BP2O8(OH], has been obtained by ionothermal synthesis from KH2PO4, FeCl3∙4H2O, H3BO3 and [C4mpyr]Br (1-butyl-1-methylpyrrolidinium bromide. Single-crystal X-ray diffraction analysis shows that KFe[BP2O8(OH] (monoclinic, P21/c, a = 9.372(2 Å , b = 8.146(2Å , c = 9.587(2 Å, β = 101.18(3°, V = 718.0(2Å3 and Z = 4 has a three-dimensional (3-D framework structure composed by {Fe(IIIO5(OH} octahedra as well as {BO3(OH} and {PO4} tetrahedra. As anionic structural sub-unit, KFe[BP2O8(OH], contains an infinite open-branched {[BP2O8(OH]4-} chain which is formed by alternating {BO3(OH} and {PO4} tetrahedra. {Fe(IIIO5(OH} octahedra share common O corners with five phosphate tetrahedra and the OH corner links to the hydrogen borate group to give a 3D framework. The negative charges of the inorganic framework are balanced by K+ ions.

Effect of CPAP Withdrawal on BP in OSA: Data from Three Randomized Controlled Trials.

Science.gov (United States)

Schwarz, Esther I; Schlatzer, Christian; Rossi, Valentina A; Stradling, John R; Kohler, Malcolm

2016-12-01

Based on meta-analyses, the BP-lowering effect of CPAP therapy in patients with OSA is reported to be approximately 2 to 3 mm Hg. This figure is derived from heterogeneous trials, which are often limited by poor CPAP adherence, and thus the treatment effect may possibly be underestimated. We analyzed morning BP data from three randomized controlled CPAP withdrawal trials, which included only patients with optimal CPAP compliance. Within the three trials, 149 patients with OSA who were receiving CPAP were randomized to continue therapeutic CPAP (n = 65) or to withdraw CPAP (n = 84) for 2 weeks. Morning BP was measured at home before and after sleep studies in the hospital. CPAP withdrawal was associated with a return of OSA (apnea-hypopnea index [AHI] at a baseline of 2.8/h and at follow-up of 33.2/h). Office systolic BP (SBP) increased in the CPAP withdrawal group compared with the CPAP continuation group by +5.4 mm Hg (95% CI, 1.8-8.9 mm Hg; P = .003) and in the home SBP group by +9.0 mm Hg (95% CI, 5.7-12.3 mm Hg; P CPAP withdrawal results in a clinically relevant increase in BP, which is considerably higher than in conventional CPAP trials; it is also underestimated when office BP is used. Greater OSA severity is associated with a higher BP rise in response to CPAP withdrawal. ClinicalTrials.gov; No.: NCT01332175 and NCT01797653) URL: www.clinicaltrials.gov and ISRCTN registry (ISRCTN 93153804) URL: http://www.isrctn.com/. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC

Directory of Open Access Journals (Sweden)

Hanane Ennajdaoui

2016-05-01

Full Text Available Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3 expression correlates with malignancy, but its role(s in pathogenesis remains enigmatic. We interrogated the IGF2BP3-RNA interaction network in pancreatic ductal adenocarcinoma (PDAC cells. Using a combination of genome-wide approaches, we have identified 164 direct mRNA targets of IGF2BP3. These transcripts encode proteins enriched for functions such as cell migration, proliferation, and adhesion. Loss of IGF2BP3 reduced PDAC cell invasiveness and remodeled focal adhesion junctions. Individual nucleotide resolution crosslinking immunoprecipitation (iCLIP revealed significant overlap of IGF2BP3 and microRNA (miRNA binding sites. IGF2BP3 promotes association of the RNA-induced silencing complex (RISC with specific transcripts. Our results show that IGF2BP3 influences a malignancy-associated RNA regulon by modulating miRNA-mRNA interactions.

IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC.

Science.gov (United States)

Ennajdaoui, Hanane; Howard, Jonathan M; Sterne-Weiler, Timothy; Jahanbani, Fereshteh; Coyne, Doyle J; Uren, Philip J; Dargyte, Marija; Katzman, Sol; Draper, Jolene M; Wallace, Andrew; Cazarez, Oscar; Burns, Suzanne C; Qiao, Mei; Hinck, Lindsay; Smith, Andrew D; Toloue, Masoud M; Blencowe, Benjamin J; Penalva, Luiz O F; Sanford, Jeremy R

2016-05-31

Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) expression correlates with malignancy, but its role(s) in pathogenesis remains enigmatic. We interrogated the IGF2BP3-RNA interaction network in pancreatic ductal adenocarcinoma (PDAC) cells. Using a combination of genome-wide approaches, we have identified 164 direct mRNA targets of IGF2BP3. These transcripts encode proteins enriched for functions such as cell migration, proliferation, and adhesion. Loss of IGF2BP3 reduced PDAC cell invasiveness and remodeled focal adhesion junctions. Individual nucleotide resolution crosslinking immunoprecipitation (iCLIP) revealed significant overlap of IGF2BP3 and microRNA (miRNA) binding sites. IGF2BP3 promotes association of the RNA-induced silencing complex (RISC) with specific transcripts. Our results show that IGF2BP3 influences a malignancy-associated RNA regulon by modulating miRNA-mRNA interactions. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGF BP-3 and the hypertensive disorders of pregnancy.

LENUS (Irish Health Repository)

Cooley, Sharon M

2012-02-01

OBJECTIVE: To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational hypertension and pre-eclampsia (PET). METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a University teaching hospital in London. Statistical analysis was performed using commercial software (SPSS for Windows, version 6.1, SPSS, Chicago, IL), with P < 0.05 as significant. Maternal IGF 1, IGF 2 and IGF BP-3 were assessed on maternal blood at booking. Blood pressure was checked at each visit in conjunction with urine analysis. The Davey & MacGillivray 1988 classification system was used in making the diagnosis of PET. RESULTS: There was no significant correlation between maternal IGF-1 or IGFBP-3 levels and gestational hypertension or PET. However, a significant positive correlation does exist between maternal IGF-2 levels and PET. CONCLUSIONS: Maternal IGF-2 has a significant positive correlation with PET.

Conformational Dynamics of apo-GlnBP Revealed by Experimental and Computational Analysis

KAUST Repository

Feng, Yitao

2016-10-13

The glutamine binding protein (GlnBP) binds l-glutamine and cooperates with its cognate transporters during glutamine uptake. Crystal structure analysis has revealed an open and a closed conformation for apo- and holo-GlnBP, respectively. However, the detailed conformational dynamics have remained unclear. Herein, we combined NMR spectroscopy, MD simulations, and single-molecule FRET techniques to decipher the conformational dynamics of apo-GlnBP. The NMR residual dipolar couplings of apo-GlnBP were in good agreement with a MD-derived structure ensemble consisting of four metastable states. The open and closed conformations are the two major states. This four-state model was further validated by smFRET experiments and suggests the conformational selection mechanism in ligand recognition of GlnBP. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Fault Diagnosis of Power System Based on Improved Genetic Optimized BP-NN

Directory of Open Access Journals (Sweden)

Yuan Pu

2015-01-01

Full Text Available BP neural network (Back-Propagation Neural Network, BP-NN is one of the most widely neural network models and is applied to fault diagnosis of power system currently. BP neural network has good self-learning and adaptive ability and generalization ability, but the operation process is easy to fall into local minima. Genetic algorithm has global optimization features, and crossover is the most important operation of the Genetic Algorithm. In this paper, we can modify the crossover of traditional Genetic Algorithm, using improved genetic algorithm optimized BP neural network training initial weights and thresholds, to avoid the problem of BP neural network fall into local minima. The results of analysis by an example, the method can efficiently diagnose network fault location, and improve fault-tolerance and grid fault diagnosis effect.

Conformational Dynamics of apo-GlnBP Revealed by Experimental and Computational Analysis

KAUST Repository

Feng, Yitao; Zhang, Lu; Wu, Shaowen; Liu, Zhijun; Gao, Xin; Zhang, Xu; Liu, Maili; Liu, Jianwei; Huang, Xuhui; Wang, Wenning

2016-01-01

The glutamine binding protein (GlnBP) binds l-glutamine and cooperates with its cognate transporters during glutamine uptake. Crystal structure analysis has revealed an open and a closed conformation for apo- and holo-GlnBP, respectively. However, the detailed conformational dynamics have remained unclear. Herein, we combined NMR spectroscopy, MD simulations, and single-molecule FRET techniques to decipher the conformational dynamics of apo-GlnBP. The NMR residual dipolar couplings of apo-GlnBP were in good agreement with a MD-derived structure ensemble consisting of four metastable states. The open and closed conformations are the two major states. This four-state model was further validated by smFRET experiments and suggests the conformational selection mechanism in ligand recognition of GlnBP. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Comparison of Akt/mTOR/4E-BP1 pathway signal activation and mutations of PIK3CA in Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative carcinomas.

Science.gov (United States)

Iwasaki, Takeshi; Matsushita, Michiko; Nonaka, Daisuke; Kuwamoto, Satoshi; Kato, Masako; Murakami, Ichiro; Nagata, Keiko; Nakajima, Hideki; Sano, Shigetoshi; Hayashi, Kazuhiko

2015-02-01

Merkel cell polyomavirus (MCPyV) integrates monoclonally into the genomes of approximately 80% of Merkel cell carcinomas (MCCs), affecting their clinicopathological features. The molecular mechanisms underlying MCC development after MCPyV infection remain unclear. We investigated the association of MCPyV infection with activation of the Akt/mammalian target of rapamycin (mTOR)/4E-binding protein 1 (4E-BP1) signaling pathway in MCCs to elucidate the role of these signal transductions and to identify molecular targets for treatment. We analyzed the molecular and pathological characteristics of 41 MCPyV-positive and 27 MCPyV-negative MCCs. Expression of mTOR, TSC1, and TSC2 messenger RNA was significantly higher in MCPyV-negative MCCs, and Akt (T308) phosphorylation also was significantly higher (92% vs 66%; P = .019), whereas 4E-BP1 (S65 and T70) phosphorylation was common in both MCC types (92%-100%). The expression rates of most other tested signals were high (60%-100%) and not significantly correlated with MCPyV large T antigen expression. PIK3CA mutations were observed more frequently in MCPyV-positive MCCs (6/36 [17%] vs 2/20 [10%]). These results suggest that protein expression (activation) of most Akt/mTOR/4E-BP1 pathway signals was not significantly different in MCPyV-positive and MCPyV-negative MCCs, although these 2 types may differ in tumorigenesis, and MCPyV-negative MCCs showed significantly more frequent p-Akt (T308) activation. Therefore, certain Akt/mTOR/4E-BP1 pathway signals could be novel therapeutic targets for MCC regardless of MCPyV infection status. Copyright © 2015 Elsevier Inc. All rights reserved.

Crystal structure of the G3BP2 NTF2-like domain in complex with a canonical FGDF motif peptide

DEFF Research Database (Denmark)

Kristensen, Ole

2015-01-01

-terminal domains of the G3BP1 and Rasputin proteins. Recently, a subset of G3BP interacting proteins was recognized to share a common sequence motif, FGDF. The most studied binding partners, USP10 and viral nsP3, interfere with essential G3BP functions related to assembly of cellular stress granules. Reported...

Tyrosine phosphorylation of 3BP2 is indispensable for the interaction with VAV3 in chicken DT40 cells.

Science.gov (United States)

Chihara, Kazuyasu; Kimura, Yukihiro; Honjoh, Chisato; Yamauchi, Shota; Takeuchi, Kenji; Sada, Kiyonao

2014-03-10

Adaptor protein c-Abl SH3 domain-binding protein-2 (3BP2) is known to play regulatory roles in immunoreceptor-mediated signal transduction. We have previously demonstrated that Tyr(174), Tyr(183) and Tyr(446) in mouse 3BP2 are predominantly phosphorylated by Syk, and the phosphorylation of Tyr(183) and the Src homology 2 (SH2) domain of mouse 3BP2 are critical for B cell receptor (BCR)-induced activation of nuclear factor of activated T cells (NFAT) in human B cells. In this report, we have shown that Syk, but not Abl family protein-tyrosine kinases, is critical for BCR-mediated tyrosine phosphorylation of 3BP2 in chicken DT40 cells. Mutational analysis showed that Tyr(174), Tyr(183) and Tyr(426) of chicken 3BP2 are the major phosphorylation sites by Syk and the SH2 domain of 3BP2 is critical for tyrosine phosphorylation. In addition, phosphorylation of Tyr(426) is required for the inducible interaction with the SH2 domain of Vav3. Moreover, the expression of the mutant form of 3BP2 in which Tyr(426) was substituted to Phe resulted in the reduction in BCR-mediated Rac1 activation, when compared with the case of wild-type. Altogether, these data suggest that 3BP2 is involved in the activation of Rac1 through the regulation of Vav3 by Syk-dependent phosphorylation of Tyr(426) following BCR stimulation. Copyright © 2014 Elsevier Inc. All rights reserved.

Mechanistic insights into the role of prenyl-binding protein PrBP/δ in membrane dissociation of phosphodiesterase 6

KAUST Repository

Qureshi, Bilal M.

2018-01-02

Isoprenylated proteins are associated with membranes and their inter-compartmental distribution is regulated by solubilization factors, which incorporate lipid moieties in hydrophobic cavities and thereby facilitate free diffusion during trafficking. Here we report the crystal structure of a solubilization factor, the prenyl-binding protein (PrBP/δ), at 1.81 Å resolution in its ligand-free apo-form. Apo-PrBP/δ harbors a preshaped, deep hydrophobic cavity, capacitating apo-PrBP/δ to readily bind its prenylated cargo. To investigate the molecular mechanism of cargo solubilization we analyzed the PrBP/δ-induced membrane dissociation of rod photoreceptor phosphodiesterase (PDE6). The results suggest that PrBP/δ exclusively interacts with the soluble fraction of PDE6. Depletion of soluble species in turn leads to dissociation of membrane-bound PDE6, as both are in equilibrium. This

Mechanistic insights into the role of prenyl-binding protein PrBP/δ in membrane dissociation of phosphodiesterase 6

KAUST Repository

Qureshi, Bilal M.; Schmidt, Andrea; Behrmann, Elmar; Bü rger, Jö rg; Mielke, Thorsten; Spahn, Christian M. T.; Heck, Martin; Scheerer, Patrick

2018-01-01

Isoprenylated proteins are associated with membranes and their inter-compartmental distribution is regulated by solubilization factors, which incorporate lipid moieties in hydrophobic cavities and thereby facilitate free diffusion during trafficking. Here we report the crystal structure of a solubilization factor, the prenyl-binding protein (PrBP/δ), at 1.81 Å resolution in its ligand-free apo-form. Apo-PrBP/δ harbors a preshaped, deep hydrophobic cavity, capacitating apo-PrBP/δ to readily bind its prenylated cargo. To investigate the molecular mechanism of cargo solubilization we analyzed the PrBP/δ-induced membrane dissociation of rod photoreceptor phosphodiesterase (PDE6). The results suggest that PrBP/δ exclusively interacts with the soluble fraction of PDE6. Depletion of soluble species in turn leads to dissociation of membrane-bound PDE6, as both are in equilibrium. This

BP pääseb lekkest kuiva nahaga / Heiki Suurkask

Index Scriptorium Estoniae

Suurkask, Heiki, 1972-

2010-01-01

BP saab peagi valmis tagavara-naftapuuraugu, lekkinud puuraugule õnnestus peale valada betoonkiht. Autor märgib, et tegelikult ei saa USA võimud ühtegi edusammu naftalekke peatamisel selgelt oma nimele kirjutada ning ainsaks kaotajaks selles lekkes peale looduse ja kalurite paistab olevat ameti kaotav BP juht Tony Hatward

200-BP-5 operable unit Technical Baseline report

International Nuclear Information System (INIS)

Jacques, I.D.; Kent, S.K.

1991-10-01

This report supports development of a remedial investigation/feasibility study work plan for the 200-BP-5 operable unit. The report summarizes baseline information for waste sites and unplanned release sites located in the 200-BP-5 operable unit. The sites were investigated by the Technical Baseline Section of the Environmental Engineering Group, Westinghouse Hanford Company (Westinghouse Hanford). The investigation consisted of review and evaluation of current and historical Hanford Site reports, drawings, and photographs, and was supplemented with recent inspections of the Hanford Site and employee interviews. No field investigations or sampling were conducted

Advertising as Insurance or Commitment? Evidence from the BP Oil Spill

OpenAIRE

Lint Barrage; Eric Chyn; Justine Hastings

2014-01-01

This paper explores how advertising impacts the consumer response to news about unobserved product quality. Specifically, we estimate how British Petroleum’s (BP) 2000-2008 “Beyond Petroleum” advertising campaign affected the impact of the 2010 BP oil spill. We find that BP station margins declined by 4.2 cents per gallon, and volumes declined by 3.6 percent after the spill. However, pre-spill advertising significantly dampened the price response in the short-run, and reduced the fraction of ...

Association mapping of the high-grade myopia MYP3 locus reveals novel candidates UHRF1BP1L, PTPRR, and PPFIA2

DEFF Research Database (Denmark)

Hawthorne, Felicia; Feng, Sheng; Metlapally, Ravikanth

2013-01-01

PURPOSE: Myopia, or nearsightedness, is a common ocular genetic disease for which over 20 candidate genomic loci have been identified. The high-grade myopia locus, MYP3, has been reported on chromosome 12q21-23 by four independent linkage studies. METHODS: We performed a genetic association study...... statistically significant SNPs rs4764971, also found by qualitative testing (P = 3.1 × 10(-6)); rs7134216, in the 3' untranslated region (UTR) of DEPDC4 (P = 5.4 × 10(-7)); and rs17306116, an intronic SNP within PPFIA2 (P Independently conducted whole genome expression array analyses identified...... protein tyrosine phosphatase genes PTPRR and PPFIA2, which are in the same gene family, as differentially expressed in normal rapidly growing fetal relative to normal adult ocular tissue (confirmed by RT-qPCR). CONCLUSIONS: In an independent high-grade myopia cohort, an intronic SNP in UHRF1BP1L, rs...

Interactions of the human MCM-BP protein with MCM complex components and Dbf4.

Directory of Open Access Journals (Sweden)

Tin Nguyen

Full Text Available MCM-BP was discovered as a protein that co-purified from human cells with MCM proteins 3 through 7; results which were recapitulated in frogs, yeast and plants. Evidence in all of these organisms supports an important role for MCM-BP in DNA replication, including contributions to MCM complex unloading. However the mechanisms by which MCM-BP functions and associates with MCM complexes are not well understood. Here we show that human MCM-BP is capable of interacting with individual MCM proteins 2 through 7 when co-expressed in insect cells and can greatly increase the recovery of some recombinant MCM proteins. Glycerol gradient sedimentation analysis indicated that MCM-BP interacts most strongly with MCM4 and MCM7. Similar gradient analyses of human cell lysates showed that only a small amount of MCM-BP overlapped with the migration of MCM complexes and that MCM complexes were disrupted by exogenous MCM-BP. In addition, large complexes containing MCM-BP and MCM proteins were detected at mid to late S phase, suggesting that the formation of specific MCM-BP complexes is cell cycle regulated. We also identified an interaction between MCM-BP and the Dbf4 regulatory component of the DDK kinase in both yeast 2-hybrid and insect cell co-expression assays, and this interaction was verified by co-immunoprecipitation of endogenous proteins from human cells. In vitro kinase assays showed that MCM-BP was not a substrate for DDK but could inhibit DDK phosphorylation of MCM4,6,7 within MCM4,6,7 or MCM2-7 complexes, with little effect on DDK phosphorylation of MCM2. Since DDK is known to activate DNA replication through phosphorylation of these MCM proteins, our results suggest that MCM-BP may affect DNA replication in part by regulating MCM phosphorylation by DDK.

Interactions of the human MCM-BP protein with MCM complex components and Dbf4.

Science.gov (United States)

Nguyen, Tin; Jagannathan, Madhav; Shire, Kathy; Frappier, Lori

2012-01-01

MCM-BP was discovered as a protein that co-purified from human cells with MCM proteins 3 through 7; results which were recapitulated in frogs, yeast and plants. Evidence in all of these organisms supports an important role for MCM-BP in DNA replication, including contributions to MCM complex unloading. However the mechanisms by which MCM-BP functions and associates with MCM complexes are not well understood. Here we show that human MCM-BP is capable of interacting with individual MCM proteins 2 through 7 when co-expressed in insect cells and can greatly increase the recovery of some recombinant MCM proteins. Glycerol gradient sedimentation analysis indicated that MCM-BP interacts most strongly with MCM4 and MCM7. Similar gradient analyses of human cell lysates showed that only a small amount of MCM-BP overlapped with the migration of MCM complexes and that MCM complexes were disrupted by exogenous MCM-BP. In addition, large complexes containing MCM-BP and MCM proteins were detected at mid to late S phase, suggesting that the formation of specific MCM-BP complexes is cell cycle regulated. We also identified an interaction between MCM-BP and the Dbf4 regulatory component of the DDK kinase in both yeast 2-hybrid and insect cell co-expression assays, and this interaction was verified by co-immunoprecipitation of endogenous proteins from human cells. In vitro kinase assays showed that MCM-BP was not a substrate for DDK but could inhibit DDK phosphorylation of MCM4,6,7 within MCM4,6,7 or MCM2-7 complexes, with little effect on DDK phosphorylation of MCM2. Since DDK is known to activate DNA replication through phosphorylation of these MCM proteins, our results suggest that MCM-BP may affect DNA replication in part by regulating MCM phosphorylation by DDK.

Validation of the Samsung SBM-100A and Microlife BP 3BU1-5 wrist blood pressure measuring devices in adults according to the International Protocol.

Science.gov (United States)

Altunkan, Sekip; Ilman, Nevzat; Altunkan, Erkan

2007-04-01

A variety of automatic blood measurement devices with diverse features have been introduced to the medical markets recently. Among these devices, models that measure at the wrist have become increasingly popular in self measurements. The objective of this study was to evaluate the accuracy of the Samsung SBM-100A and Microlife BP 3BU1-5 wrist blood pressure devices against the mercury sphygmomanometer in adults according to the International Protocol criteria. Fifty-four patients over 30 years of age were studied and classified based on the International Protocol range. Blood pressure measurements at the wrist with the Samsung SBM-100A and Microlife BP 3BU1-5 were compared with the results obtained by two trained observers using a mercury sphygmomanometer. Nine sequential blood pressure measurements were taken. A total of 33 participants with randomly distributed arm circumferences were selected for both of the validation studies. During each validation study, 99 measurements were obtained for comparison from 33 participants. The first phase was performed on 15 participants and if the device passed this phase, 18 more participants were selected. Mean discrepancies and standard deviations of the device-sphygmomanometer were 0.9+/-9.2 and -2.7+/-9.3 mmHg for systolic blood pressure and -1.4+/-8.0 mmHg and 1.4+/-5.7 for diastolic blood pressure in the Samsung and Microlife study groups, respectively. The Samsung SBM-100A passed Phase 1 in 15 participants. Despite the fact that Microlife BP 3BU1-5 passed Phase 1 for diastolic pressure, it failed according to the systolic pressure criteria. Eighteen patients were added and Phase 2 was continued, in which Samsung SBM-100A failed to meet the criteria of Phases 2.1 and 2.2 for adults in systolic and diastolic blood pressure. It was found that the Microlife BP 3BU1-5 does not meet the criteria of either of Phases 2.1 and 2.2 for systolic blood pressure and Phase 2.2 for diastolic blood pressure. In this study, Samsung SBM

Bp'S Baku-Tbilisi-Ceyhan pipeline: the new corporate colonialism.

Science.gov (United States)

Marriott, James; Muttitt, Greg

2006-01-01

An international campaign was waged questioning the benefits of BP's Baku-Tbilisi-Ceyhan pipeline in an effort to avoid a "zone of sacrifice" there. This article is an offshoot of that effort and explains the contemporary struggle over the pipeline project. The authors describe the project's background and evaluate the actual and potential impacts of the project in which they consider eight areas. They also assess BP's capacity to confront resistance to the pipeline.

Contrasting Pathology of the Stress Granule Proteins TIA-1 and G3BP in Tauopathies

Science.gov (United States)

Vanderweyde, Tara; Yu, Haung; Varnum, Megan; Liu-Yesucevitz, Liqun; Citro, Allison; Ikezu, Tsuneya; Duff, Karen; Wolozin, Benjamin

2012-01-01

Stress induces aggregation of RNA-binding proteins to form inclusions, termed stress granules (SGs). Recent evidence suggests that SG proteins also colocalize with neuropathological structures, but whether this occurs in Alzheimer’s disease is unknown. We examined the relationship between SG proteins and neuropathology in brain tissue from P301L Tau transgenic mice, as well as in cases of Alzheimer’s disease and FTDP-17. The pattern of SG pathology differs dramatically based on the RNA-binding protein examined. SGs positive for T-cell intracellular antigen-1 (TIA-1) or tristetraprolin (TTP) initially do not colocalize with tau pathology, but then merge with tau inclusions as disease severity increases. In contrast, G3BP (ras GAP-binding protein) identifies a novel type of molecular pathology that shows increasing accumulation in neurons with increasing disease severity, but often is not associated with classic markers of tau pathology. TIA-1 and TTP both bind phospho-tau, and TIA-1 overexpression induces formation of inclusions containing phospho-tau. These data suggest that SG formation might stimulate tau pathophysiology. Thus, study of RNA-binding proteins and SG biology highlights novel pathways interacting with the pathophysiology of AD, providing potentially new avenues for identifying diseased neurons and potentially novel mechanisms regulating tau biology. PMID:22699908

Studies of the viral binding proteins of shrimp BP53, a receptor of white spot syndrome virus.

Science.gov (United States)

Li, Chen; Gao, Xiao-Xiao; Huang, Jie; Liang, Yan

2016-02-01

The specific binding between viral attachment proteins (VAPs) of a virus and its cellular receptors on host cells mediates virus entry into host cells, which triggers subsequent viral infections. Previous studies indicate that F1 ATP synthase β subunit (named BP53), is found on the surface of shrimp cells and involved in white spot syndrome virus (WSSV) infection by functioning as a potential viral receptor. Herein, in a far-western blotting assay, three WSSV proteins with molecular weights of 28 kDa, 37 kDa, and >50 kDa were found to interact with BP53. The 28 kDa and 37 kDa proteins were identified as the envelope protein VP28 and VP37 of WSSV respectively, which could be recognized by the polyclonal antibodies. Enzyme-linked immunosorbent binding assays revealed that VP37 contributed to almost 80% of the binding capability for BP53 compared with the same amount of total WSSV protein. The relationship between BP53 and its complementary interacting protein, VP37, was visualized using a co-localization assay. Bound VP37 on the cell surface co-localized with BP53 and shared a similar subcellular location on the outer surface of shrimp cells. Pearson's correlation coefficients reached to 0.67 ± 0.05 and the Mander's overlap coefficients reached 0.70 ± 0.05, which indicated a strong relationship between the localization of BP53 and bound rVP37. This provides evidence for an interaction between BP53 and VP37 obtained at the molecular and cellular levels, supporting the hypothesis that BP53 serves as a receptor for WSSV by binding to VP37. The identification of the viral binding proteins of shrimp BP53 is helpful for better understanding the pathogenic mechanisms of WSSV to infect shrimp at the cellular level. Copyright © 2016 Elsevier Inc. All rights reserved.

Identification of transcripts regulated by CUG-BP, Elav-like family member 1 (CELF1 in primary embryonic cardiomyocytes by RNA-seq

Directory of Open Access Journals (Sweden)

Yotam Blech-Hermoni

2015-12-01

Full Text Available CUG-BP, Elav-like family member 1 (CELF1 is a multi-functional RNA binding protein that regulates pre-mRNA alternative splicing in the nucleus, as well as polyadenylation status, mRNA stability, and translation in the cytoplasm [1]. Dysregulation of CELF1 has been implicated in cardiomyopathies in myotonic dystrophy type 1 and diabetes [2–5], but the targets of CELF1 regulation in the heart have not been systematically investigated. We previously demonstrated that in the developing heart CELF1 expression is restricted to the myocardium and peaks during embryogenesis [6–8]. To identify transcripts regulated by CELF1 in the embryonic myocardium, RNA-seq was used to compare the transcriptome of primary embryonic cardiomyocytes following siRNA-mediated knockdown of CELF1 to that of controls. Raw data files of the RNA-seq reads have been deposited in NCBI's Gene Expression Omnibus [9] under the GEO Series accession number GSE67360. These data can be used to identify transcripts whose levels or alternative processing (i.e., alternative splicing or polyadenylation site usage are regulated by CELF1, and should provide insight into the pathways and processes modulated by this important RNA binding protein during normal heart development and during cardiac pathogenesis.

Microwaves from GSM mobile telephones affect 53BP1 and gamma-H2AX foci in human lymphocytes from hypersensitive and healthy persons.

Science.gov (United States)

Markovà, Eva; Hillert, Lena; Malmgren, Lars; Persson, Bertil R R; Belyaev, Igor Y

2005-09-01

The data on biologic effects of nonthermal microwaves (MWs) from mobile telephones are diverse, and these effects are presently ignored by safety standards of the International Commission for Non-Ionizing Radiation Protection (ICNIRP). In the present study, we investigated effects of MWs of Global System for Mobile Communication (GSM) at different carrier frequencies on human lymphocytes from healthy persons and from persons reporting hypersensitivity to electromagnetic fields (EMFs). We measured the changes in chromatin conformation, which are indicative of stress response and genotoxic effects, by the method of anomalous viscosity time dependence, and we analyzed tumor suppressor p53-binding protein 1 (53BP1) and phosphorylated histone H2AX (gamma-H2AX), which have been shown to colocalize in distinct foci with DNA double-strand breaks (DSBs), using immunofluorescence confocal laser microscopy. We found that MWs from GSM mobile telephones affect chromatin conformation and 53BP1/gamma-H2AX foci similar to heat shock. For the first time, we report here that effects of MWs from mobile telephones on human lymphocytes are dependent on carrier frequency. On average, the same response was observed in lymphocytes from hypersensitive and healthy subjects.

Drosophila C-terminal binding protein, dCtBP is required for sensory organ prepattern and sharpens proneural transcriptional activity of the GATA factor Pnr.

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Biryukova, Inna; Heitzler, Pascal

2008-11-01

The peripheral nervous system is required for animals to detect and to relay environmental stimuli to central nervous system for the information processing. In Drosophila, the precise spatial and temporal expression of two proneural genes achaete (ac) and scute (sc), is necessary for development of the sensory organs. Here we present an evidence that the transcription co-repressor, dCtBP acts as a negative regulator of sensory organ prepattern. Loss of dCtBP function mutant exhibits ectopic sensory organs, while overexpression of dCtBP results in a dramatic loss of sensory organs. These phenotypes are correlated with mis-emerging of sensory organ precursors and perturbated expression of proneural transcription activator Ac. Mammalian CtBP-1 was identified via interaction with the consensus motif PXDLSX(K/R) of adenovirus E1A oncoprotein. We demonstrated that dCtBP binds directly to PLDLS motif of Drosophila Friend of GATA-1 protein, U-shaped and sharpens the adult sensory organ development. Moreover, we found that dCtBP mediates multivalent interaction with the GATA transcriptional activator Pannier and acts as a direct co-repressor of the Pannier-mediated activation of proneural genes. We demonstrated that Pannier genetically interacts with dCtBP-interacting protein HDAC1, suggesting that the dCtBP-dependent regulation of Pannier activity could utilize a repressive mechanism involving alteration of local chromatine structure.

Radiosensitivity evaluation of Human tumor cell lines by detecting 4977bp deletion in mitochondrial DNA

International Nuclear Information System (INIS)

Zhang Yipei

2009-01-01

Objective: To explore the feasibility of determining radiosensitivity of human tumor cell lines in vitro using the assay of mtDNA4977bp deletion. Methods: Three human tumor cell lines were selected in this study, HepG 2 , EC-9706 and MCF-7. The surviving fraction(SF), the ratio of mtDNA4977bp deletion and DNA damage were detected by MTT assay and nested PCR technique respectively. Results: MTT assay: The SF of HepG 2 and EC-9706 after irradiated by 2, 4and 8Gy was lower significantly than that of MCF-7, which showed that the radiosensitivity of HepG 2 and EC-9706 was higher than that of MCF-7. But there was no statistical difference of SF between HepG 2 and EC-9706. PCR method:The differences on mtDNA 4977bp deletion in mitochondrial DNA among HepG 2 , EC-9706 and MCF-7 were not significant after 1Gy and 4Gy γ-ray irradiation. The ratio of 4977bp deletion in mitochondrial DNA of HepG 2 and EC-9706 increased while that of MCF-7 decreased after 8Gy irradiation. The ratio of mtDNA 4977bp deletion of HepG 2 and EC-9706 was higher significantly than that of MCF-7, which implies that the radiosensitivity of HepG 2 and EC-9706 was higher than that of MCF -7. Conclusion: As a new biological marker, mtDNA4977bp deletion may be hopeful to evaluate the radiosensitivity of tumor cells more objectively and exactly. (authors)

Crystal structures of Lymnaea stagnalis AChBP in complex with neonicotinoid insecticides imidacloprid and clothianidin.

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Ihara, Makoto; Okajima, Toshihide; Yamashita, Atsuko; Oda, Takuma; Hirata, Koichi; Nishiwaki, Hisashi; Morimoto, Takako; Akamatsu, Miki; Ashikawa, Yuji; Kuroda, Shun'ichi; Mega, Ryosuke; Kuramitsu, Seiki; Sattelle, David B; Matsuda, Kazuhiko

2008-06-01

Neonicotinoid insecticides, which act on nicotinic acetylcholine receptors (nAChRs) in a variety of ways, have extremely low mammalian toxicity, yet the molecular basis of such actions is poorly understood. To elucidate the molecular basis for nAChR-neonicotinoid interactions, a surrogate protein, acetylcholine binding protein from Lymnaea stagnalis (Ls-AChBP) was crystallized in complex with neonicotinoid insecticides imidacloprid (IMI) or clothianidin (CTD). The crystal structures suggested that the guanidine moiety of IMI and CTD stacks with Tyr185, while the nitro group of IMI but not of CTD makes a hydrogen bond with Gln55. IMI showed higher binding affinity for Ls-AChBP than that of CTD, consistent with weaker CH-pi interactions in the Ls-AChBP-CTD complex than in the Ls-AChBP-IMI complex and the lack of the nitro group-Gln55 hydrogen bond in CTD. Yet, the NH at position 1 of CTD makes a hydrogen bond with the backbone carbonyl of Trp143, offering an explanation for the diverse actions of neonicotinoids on nAChRs.

Dietary patterns, nutrition knowledge and lifestyle: associations with blood pressure in a sample of Australian adults (the Food BP study).

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Khalesi, S; Sharma, S; Irwin, C; Sun, J

2016-10-01

This study examined the association between dietary patterns, nutrition knowledge and lifestyle with blood pressure (BP) in a sample of Australian adults. Adults with normal and high BP were included in a cross-sectional study. Dietary intake data was collected using a Food Frequency Questionnaire. Nutrition knowledge and lifestyle surveys were included in the questionnaire. Dietary patterns were extracted using factor analysis followed by cluster analysis. Associations were analysed using logistic regression. Four hundred and seven participants were included. Three dietary patterns were identified: Western; Snack and alcohol; and Balanced. Participants with high BP had a higher intake of Western and a lower intake of Balanced dietary pattern. A significant and higher frequency of discretionary foods and oils consumption, as well as lower nutrition knowledge score and activity frequency, were observed in the high BP group. Regression analysis indicated that the intake of Western and Snack and alcohol dietary patterns increases the likelihood of having high BP by 2.40 (95% confidence interval (CI): 1.28-4.49) and 2.76 (95% CI: 1.52-5.00), respectively, when nutrition knowledge and lifestyle were controlled for as moderator variables. The likelihood of high BP was not associated with nutrition knowledge, but increased with physical inactivity. This study indicates that poor dietary patterns and inactivity are associated with increases in the likelihood of high BP, and the association is not influenced by nutrition knowledge. These findings indicate the importance of developing public health strategies with an emphasis on improving the dietary patterns of individuals to prevent and control high BP in Australian adults.

Genetic analysis of plant endophytic Pseudomonas putida BP25 and chemo-profiling of its antimicrobial volatile organic compounds.

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Sheoran, Neelam; Valiya Nadakkakath, Agisha; Munjal, Vibhuti; Kundu, Aditi; Subaharan, Kesavan; Venugopal, Vibina; Rajamma, Suseelabhai; Eapen, Santhosh J; Kumar, Aundy

2015-04-01

Black pepper associated bacterium BP25 was isolated from root endosphere of apparently healthy cultivar Panniyur-5 that protected black pepper against Phytophthora capsici and Radopholus similis - the major production constraints. The bacterium was characterized and mechanisms of its antagonistic action against major pathogens are elucidated. The polyphasic phenotypic analysis revealed its identity as Pseudomonas putida. Multi locus sequence typing revealed that the bacterium shared gene sequences with several other isolates representing diverse habitats. Tissue localization assays exploiting green fluorescence protein expression clearly indicated that PpBP25 endophytically colonized not only its host plant - black pepper, but also other distantly related plants such as ginger and arabidopsis. PpBP25 colonies could be enumerated from internal tissues of plants four weeks post inoculation indicated its stable establishment and persistence in the plant system. The bacterium inhibited broad range of pathogens such as Phytophthora capsici, Pythium myriotylum, Giberella moniliformis, Rhizoctonia solani, Athelia rolfsii, Colletotrichum gloeosporioides and plant parasitic nematode, Radopholus similis by its volatile substances. GC/MS based chemical profiling revealed presence of Heneicosane; Tetratetracontane; Pyrrolo [1,2-a] pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl); Tetracosyl heptafluorobutyrate; 1-3-Eicosene, (E)-; 1-Heneicosanol; Octadecyl trifluoroacetate and 1-Pentadecene in PpBP25 metabolite. Dynamic head space GC/MS analysis of airborne volatiles indicated the presence of aromatic compounds such as 1-Undecene;Disulfide dimethyl; Pyrazine, methyl-Pyrazine, 2,5-dimethyl-; Isoamyl alcohol; Pyrazine, methyl-; Dimethyl trisulfide, etc. The work paved way for profiling of broad spectrum antimicrobial VOCs in endophytic PpBP25 for crop protection. Copyright © 2015 Elsevier GmbH. All rights reserved.

BP Investment Exceeds $4 Bln in china

Institute of Scientific and Technical Information of China (English)

Wang Ping

2008-01-01

@@ British Petroleum (BP) recently signed a series of agreements with China including those in clean energy and wind power generation, during British Prime Minister Gordon Brown's visit to China in mid-January.

Effect of turmeric and curcumin on BP-DNA adducts.

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Mukundan, M A; Chacko, M C; Annapurna, V V; Krishnaswamy, K

1993-03-01

Many human cancers that are widely prevalent today can be prevented through modifications in life-styles, of which diet appears to be an important agent. Several dietary constituents modulate the process of carcinogenesis and prevent genotoxicity. Many plant constituents including turmeric appear to be potent antimutagens and antioxidants. Therefore the modulatory effects of turmeric and curcumin on the levels of benzo[a]pyrene induced DNA adducts in the livers of rats were studied by the newly developed 32P-postlabelling assay method. Turmeric when fed at 0.1, 0.5 and 3% and the active principle of turmeric (curcumin) when fed at a level of 0.03% in the diet for 4 weeks significantly reduced the level of BP-DNA adducts including the major adduct dG-N2-BP, formed within 24 h in response to a single i.p. injection of benzo[a]pyrene. The significance of these effects in terms of the potential anticarcinogenic effects of turmeric is discussed. Further, these results strengthen the various other biological effects of turmeric which have direct relevance to anticarcinogenesis and chemoprevention.

A genetic-demographic approach reveals a gender-specific association of SLC6A3/DAT1 40 bp-VNTR with life-expectancy.

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Hadi, Fazal; Dato, Serena; Carpi, Francesco M; Prontera, Paolo; Crucianelli, Francesca; Renda, Federica; Passarino, Giuseppe; Napolioni, Valerio

2015-06-01

Several recent lines of evidence are proving an important role for dopamine in the aging process and in the determination of life span. Components of the dopaminergic system may represent good candidates for longevity studies. Herein, we tested the possible association of the functional SLC6A3/DAT1 40-bp VNTR with life-expectancy in a healthy population of Central Italy (N = 993) by applying a genetic-demographic approach that takes into account the demographic information and different survival rates between sexes for modeling the survival of specific allele carriers in the population. Male carriers of S*/S* genotype showed a lower survival chance across most of the lifespan respect to the survival of DAT1*L-carriers (P = 0.021). The same analyses gave non-significant results in females. Several studies already reported significant sex differences in dopamine metabolism and its related biological pathways. Thus, we can hypothesize that the SLC6A3/DAT1 40 bp-VNTR may affect life expectancy in a sex-specific way. Moreover, it is conceivable that DAT1 S*/S* carriers, who are prone to assume "risk" type behaviors, may be dropped out of the "healthy" population by a sort of "demographic selection".

Primary quantitative analysis of the mtDNA4977bp deletion induced by lonizing radiation in human peripheral blood u-sing real-time PCR

International Nuclear Information System (INIS)

Duan Zhikai; Liu Jiangong; Guo Wanlong; Zhang Shuxian

2011-01-01

Objective: To observe the influence of mtDNA4977bp deletion induced by different dose of γ ray in human peripheral blood in order to explore the feasibility of mtDNA4977bp deletion as biodosimeter. Methods: Human peripheral blood samples were collected from three healthy donors and irradiated by γ ray, MtDNA4977bp deletion was detected by real-time PCR. Results: It indicated that that from the range of 0 ∼ 8 Gy, the relationship between mtDNA4977bp deletion and irradiation dose represents certain curvilinear correlation (Y=1.2693+1.0660X+0.0198X 2 ). Conclusion: We find that γ ray has influence on the mtDNA4977bp deletion, so it may be an important biodosmeter in future. (authors)

Association of Autoantibodies to BP180 with Disease Activity in Greek Patients with Bullous Pemphigoid

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Aikaterini Patsatsi

2012-01-01

Full Text Available 39 bullous pemphigoid (BP patients were studied to assess the clinical significance of anti-BP180 and anti-BP230 circulating autoantibodies of BP and correlate their titers with the clinical scores of the BP Disease Area Index (BPDAI and the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS as well as with the intensity of pruritus measured by the BPDAI pruritus component. All parameters were evaluated by the time of diagnosis (baseline, month 3, and month 6. Titers of anti-BP180 autoantibodies were strongly correlated with BPDAI (, and ABSIS (, values, as well as with BPDAI component for the intensity of pruritus (, at baseline. At month 3, titers of anti-BP180 autoantibodies were strongly correlated with BPDAI (, and ABSIS (, values, as well as with the BPDAI component for the intensity of pruritus (, . At month 6, titers of anti-BP180 autoantibodies were strongly correlated with BPDAI (, and ABSIS (, values, as well as with the BPDAI component for the intensity of pruritus (, . There was no statistically significant correlation between titers of anti-BP230 autoantibodies and the BPDAI, ABSIS, and BPDAI component for the intensity of pruritus at the same time points.

CHANDRA X-RAY DETECTION OF THE ENIGMATIC FIELD STAR BP Psc

International Nuclear Information System (INIS)

Kastner, Joel H.; Montez, Rodolfo; Rodriguez, David; Zuckerman, B.; Perrin, Marshall D.; Grosso, Nicolas; Forveille, Thierry; Graham, James R.

2010-01-01

BP Psc is a remarkable emission-line field star that is orbited by a dusty disk and drives a parsec-scale system of jets. We report the detection by the Chandra X-ray Observatory of a weak X-ray point source coincident with the centroids of optical/IR and submillimeter continuum emission at BP Psc. As the star's photosphere is obscured throughout the visible and near-infrared, the Chandra X-ray source likely represents the first detection of BP Psc itself. The X-rays most likely originate with magnetic activity at BP Psc and hence can be attributed either to a stellar corona or to star-disk interactions. The log of the ratio of X-ray to bolometric luminosity, log(L X /L bol ), lies in the range -5.8 to -4.2. This is smaller than log(L X /L bol ) ratios typical of low-mass, pre-main sequence stars, but is well within the log(L X /L bol ) range observed for rapidly rotating (FK Com-type) G giant stars. Hence, the Chandra results favor an exotic model wherein the disk/jet system of BP Psc is the result of its very recently engulfing a companion star or a giant planet, as the primary star ascended the giant branch.

BP Oil Company's approach to risk management

International Nuclear Information System (INIS)

Fryman, C.E.

1996-01-01

The oil and chemical industries face major challenges in deciding how to handle the numerous recommendations coming from various audits, reviews and studies conducted in the functional areas of personnel health and safety, loss prevention, and environmental protection. And, the number of recommendations continues to grow with time, as regulations and normal business requirements are met. BP Oil has developed a methodology for risk ranking the events leading to specific recommendations and then determining the cost-effectiveness of the recommendations in reducing the risk. The author completed successful pilot tests of this methodology at two of BP Oil's petroleum refineries, examining the recommendations from process hazards analyses and studies completed over the past few years. The methodology has since been implemented throughout their petroleum refining, distribution, transportation, and retail business streams

Inverse Solutionof BP Neural Network for Laser Ｒemelting Parameters

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LIU Li-jun

2017-06-01

Full Text Available Aim at highly nonlinear mapping relationship between the laser processing parameters and the melting cell body’s transverse size，a method of reverse engineering laser melting parameters by back － propagation ( BP neural network was put forward． The model was constructed by BP neural network，and the prediction error was reduced to less than 3% after training for many times． The DIEVAＲ die steel was melted by reverse engineering laser parameters，and the results show that the error was 1． 33% between the transverse dimensions of the melting cell body and the expected，the expected precision can be met well． Thermal fatigue property of the melted and non － melted DIEVAＲ die steel has been studied． The analysis about cracks growth presents that thermal fatigue property of DIEVAＲ die steel melted by the reverse engineering parameters has been greatly improved． The melting cell body could block crack effectively．

Validation of the A&D BP UB-542 wrist device for home blood pressure measurement according to the European Society of Hypertension International Protocol revision 2010.

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Saladini, Francesca; Benetti, Elisabetta; Fania, Claudio; Palatini, Paolo

2013-08-01

The objective of this study was to determine the accuracy of the A&D BP UB-542 wrist device for home blood pressure (BP) measurement according to the International Protocol of the European Society of Hypertension (ESH). Device evaluation was carried out in 33 patients. The mean age was 50.9±10.1 years, the mean systolic BP was 141.6±22.8 mmHg (range 92 : 189), the mean diastolic BP was 89.2±11.4 mmHg (range 62 : 120), the mean arm circumference was 28.8±3.2 cm (range 23-35), and the mean wrist circumference was 17.1±1.4 cm (range 14-19.5). The protocol requirements were followed precisely. The device passed all requirements, fulfilling the standards of the protocol. On average, the device overestimated the systolic BP by 1.8±7.2 mmHg and diastolic BP by 1.6±5.7 mmHg. These data show that the A&D BP UB-542 wrist device met the requirements for validation by the International Protocol and can be recommended for clinical use in the adult population.

Prediction of BP Reactivity to Talking Using Hybrid Soft Computing Approaches

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Gurmanik Kaur

2014-01-01

Full Text Available High blood pressure (BP is associated with an increased risk of cardiovascular diseases. Therefore, optimal precision in measurement of BP is appropriate in clinical and research studies. In this work, anthropometric characteristics including age, height, weight, body mass index (BMI, and arm circumference (AC were used as independent predictor variables for the prediction of BP reactivity to talking. Principal component analysis (PCA was fused with artificial neural network (ANN, adaptive neurofuzzy inference system (ANFIS, and least square-support vector machine (LS-SVM model to remove the multicollinearity effect among anthropometric predictor variables. The statistical tests in terms of coefficient of determination (R2, root mean square error (RMSE, and mean absolute percentage error (MAPE revealed that PCA based LS-SVM (PCA-LS-SVM model produced a more efficient prediction of BP reactivity as compared to other models. This assessment presents the importance and advantages posed by PCA fused prediction models for prediction of biological variables.

Prediction of BP reactivity to talking using hybrid soft computing approaches.

Science.gov (United States)

Kaur, Gurmanik; Arora, Ajat Shatru; Jain, Vijender Kumar

2014-01-01

High blood pressure (BP) is associated with an increased risk of cardiovascular diseases. Therefore, optimal precision in measurement of BP is appropriate in clinical and research studies. In this work, anthropometric characteristics including age, height, weight, body mass index (BMI), and arm circumference (AC) were used as independent predictor variables for the prediction of BP reactivity to talking. Principal component analysis (PCA) was fused with artificial neural network (ANN), adaptive neurofuzzy inference system (ANFIS), and least square-support vector machine (LS-SVM) model to remove the multicollinearity effect among anthropometric predictor variables. The statistical tests in terms of coefficient of determination (R (2)), root mean square error (RMSE), and mean absolute percentage error (MAPE) revealed that PCA based LS-SVM (PCA-LS-SVM) model produced a more efficient prediction of BP reactivity as compared to other models. This assessment presents the importance and advantages posed by PCA fused prediction models for prediction of biological variables.

A minireview of E4BP4/NFIL3 in heart failure.

Science.gov (United States)

Velmurugan, Bharath Kumar; Chang, Ruey-Lin; Marthandam Asokan, Shibu; Chang, Chih-Fen; Day, Cecilia-Hsuan; Lin, Yueh-Min; Lin, Yuan-Chuan; Kuo, Wei-Wen; Huang, Chih-Yang

2018-06-01

Heart failure (HF) remains a major cause of morbidity and mortality worldwide. The primary cause identified for HF is impaired left ventricular myocardial function, and clinical manifestations may lead to severe conditions like pulmonary congestion, splanchnic congestion, and peripheral edema. Development of new therapeutic strategies remains the need of the hour for controlling the problem of HF worldwide. Deeper insights into the molecular mechanisms involved in etiopathology of HF indicate the significant role of calcium signaling, autocrine signaling pathways, and insulin-like growth factor-1 signaling that regulates the physiologic functions of heart growth and development such as contraction, metabolism, hypertrophy, cytokine signaling, and apoptosis. In view of these facts, a transcription factor (TF) regulating the myriad of these signaling pathways may prove as a lead candidate for development of therapeutics. Adenovirus E4 promoter-binding protein (E4BP4), also known as nuclear-factor, interleukin 3 regulated (NFIL3), a type of basic leucine zipper TF, is known to regulate the signaling processes involved in the functioning of heart. The current review discusses about the expression, structure, and functional role of E4BP4 in signaling processes with emphasis on calcium signaling mechanisms, autocrine signaling, and insulin-like growth factor II receptor-mediated processes regulated by E4BP4 that may regulate the pathogenesis of HF. We propose that E4BP4, being the critical component for the regulation of the above signaling processes, may serve as a novel therapeutic target for HF, and scientific investigations are merited in this direction. © 2018 Wiley Periodicals, Inc.