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Sample records for cap-independent translation initiation

Cap-independent translation of plant viral RNAs.

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Kneller, Elizabeth L Pettit; Rakotondrafara, Aurélie M; Miller, W Allen

2006-07-01

The RNAs of many plant viruses lack a 5' cap and must be translated by a cap-independent mechanism. Here, we discuss the remarkably diverse cap-independent translation elements that have been identified in members of the Potyviridae, Luteoviridae, and Tombusviridae families, and genus Tobamovirus. Many other plant viruses have uncapped RNAs but their translation control elements are uncharacterized. Cap-independent translation elements of plant viruses differ strikingly from those of animal viruses: they are smaller (translation factors, and speculate on their mechanism of action and their roles in the virus replication cycle. Much remains to be learned about how these elements enable plant viruses to usurp the host translational machinery.
Structural and Functional Diversity of Plant Virus 3'-Cap-Independent Translation Enhancers (3'-CITEs).

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Truniger, Verónica; Miras, Manuel; Aranda, Miguel A

2017-01-01

Most of the positive-strand RNA plant viruses lack the 5'-cap and/or the poly(A)-tail that act synergistically to stimulate canonical translation of cellular mRNAs. However, they have RNA elements in the 5'- or 3'-untranslated regions of their RNAs that are required for their cap-independent translation. Cap-independent translation enhancers (CITEs) have been identified in the genomic 3'-end of viruses belonging to the family Tombusviridae and the genus Luteovirus . Seven classes of 3'-CITEs have been described to date based on their different RNA structures. They generally control the efficient formation of the translation initiation complex by varying mechanisms. Some 3'-CITEs bind eukaryotic translation initiation factors, others ribosomal subunits, bridging these to the 5'-end by different mechanisms, often long-distance RNA-RNA interactions. As previously proposed and recently found in one case in nature, 3'-CITEs are functionally independent elements that are transferable through recombination between viral genomes, leading to potential advantages for virus multiplication. In this review, the knowledge on 3'-CITEs and their functioning is updated. We also suggest that there is local structural conservation in the regions interacting with eIF4E of 3'-CITEs belonging to different classes.
Translation initiation mediated by nuclear cap-binding protein complex.

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Ryu, Incheol; Kim, Yoon Ki

2017-04-01

In mammals, cap-dependent translation of mRNAs is initiated by two distinct mechanisms: cap-binding complex (CBC; a heterodimer of CBP80 and 20)-dependent translation (CT) and eIF4E-dependent translation (ET). Both translation initiation mechanisms share common features in driving cap- dependent translation; nevertheless, they can be distinguished from each other based on their molecular features and biological roles. CT is largely associated with mRNA surveillance such as nonsense-mediated mRNA decay (NMD), whereas ET is predominantly involved in the bulk of protein synthesis. However, several recent studies have demonstrated that CT and ET have similar roles in protein synthesis and mRNA surveillance. In a subset of mRNAs, CT preferentially drives the cap-dependent translation, as ET does, and ET is responsible for mRNA surveillance, as CT does. In this review, we summarize and compare the molecular features of CT and ET with a focus on the emerging roles of CT in translation. [BMB Reports 2017; 50(4): 186-193].
Structural and Functional Diversity of Plant Virus 3′-Cap-Independent Translation Enhancers (3′-CITEs

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Verónica Truniger

2017-11-01

Full Text Available Most of the positive-strand RNA plant viruses lack the 5′-cap and/or the poly(A-tail that act synergistically to stimulate canonical translation of cellular mRNAs. However, they have RNA elements in the 5′- or 3′-untranslated regions of their RNAs that are required for their cap-independent translation. Cap-independent translation enhancers (CITEs have been identified in the genomic 3′-end of viruses belonging to the family Tombusviridae and the genus Luteovirus. Seven classes of 3′-CITEs have been described to date based on their different RNA structures. They generally control the efficient formation of the translation initiation complex by varying mechanisms. Some 3′-CITEs bind eukaryotic translation initiation factors, others ribosomal subunits, bridging these to the 5′-end by different mechanisms, often long-distance RNA–RNA interactions. As previously proposed and recently found in one case in nature, 3′-CITEs are functionally independent elements that are transferable through recombination between viral genomes, leading to potential advantages for virus multiplication. In this review, the knowledge on 3′-CITEs and their functioning is updated. We also suggest that there is local structural conservation in the regions interacting with eIF4E of 3′-CITEs belonging to different classes.
Structural and Functional Diversity of Plant Virus 3′-Cap-Independent Translation Enhancers (3′-CITEs)

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Truniger, Verónica; Miras, Manuel; Aranda, Miguel A.

2017-01-01

Most of the positive-strand RNA plant viruses lack the 5′-cap and/or the poly(A)-tail that act synergistically to stimulate canonical translation of cellular mRNAs. However, they have RNA elements in the 5′- or 3′-untranslated regions of their RNAs that are required for their cap-independent translation. Cap-independent translation enhancers (CITEs) have been identified in the genomic 3′-end of viruses belonging to the family Tombusviridae and the genus Luteovirus. Seven classes of 3′-CITEs have been described to date based on their different RNA structures. They generally control the efficient formation of the translation initiation complex by varying mechanisms. Some 3′-CITEs bind eukaryotic translation initiation factors, others ribosomal subunits, bridging these to the 5′-end by different mechanisms, often long-distance RNA–RNA interactions. As previously proposed and recently found in one case in nature, 3′-CITEs are functionally independent elements that are transferable through recombination between viral genomes, leading to potential advantages for virus multiplication. In this review, the knowledge on 3′-CITEs and their functioning is updated. We also suggest that there is local structural conservation in the regions interacting with eIF4E of 3′-CITEs belonging to different classes. PMID:29238357
Model of cap-dependent translation initiation in sea urchin: a step towards the eukaryotic translation regulation network.

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Bellé, Robert; Prigent, Sylvain; Siegel, Anne; Cormier, Patrick

2010-03-01

The large and rapid increase in the rate of protein synthesis following fertilization of the sea urchin egg has long been a paradigm of translational control, an important component of the regulation of gene expression in cells. This translational up-regulation is linked to physiological changes that occur upon fertilization and is necessary for entry into first cell division cycle. Accumulated knowledge on cap-dependent initiation of translation makes it suited and timely to start integrating the data into a system view of biological functions. Using a programming environment for system biology coupled with model validation (named Biocham), we have built an integrative model for cap-dependent initiation of translation. The model is described by abstract rules. It contains 51 reactions involved in 74 molecular complexes. The model proved to be coherent with existing knowledge by using queries based on computational tree logic (CTL) as well as Boolean simulations. The model could simulate the change in translation occurring at fertilization in the sea urchin model. It could also be coupled with an existing model designed for cell-cycle control. Therefore, the cap-dependent translation initiation model can be considered a first step towards the eukaryotic translation regulation network.
Analysis of the interacting partners eIF4F and 3'-CITE required for Melon necrotic spot virus cap-independent translation.

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Miras, Manuel; Truniger, Verónica; Querol-Audi, Jordi; Aranda, Miguel A

2017-06-01

We have shown previously that the translation of Melon necrotic spot virus (MNSV, family Tombusviridae, genus Carmovirus) RNAs is controlled by a 3'-cap-independent translation enhancer (CITE), which is genetically and functionally dependent on the eukaryotic translation initiation factor (eIF) 4E. Here, we describe structural and functional analyses of the MNSV-Mα5 3'-CITE and its translation initiation factor partner. We first mapped the minimal 3'-CITE (Ma5TE) to a 45-nucleotide sequence, which consists of a stem-loop structure with two internal loops, similar to other I-shaped 3'-CITEs. UV crosslinking, followed by gel retardation assays, indicated that Ma5TE interacts in vitro with the complex formed by eIF4E + eIF4G 980-1159 (eIF4F p20 ), but not with each subunit alone or with eIF4E + eIF4G 1003-1092 , suggesting binding either through interaction with eIF4E following a conformational change induced by its binding to eIF4G 980-1159 , or through a double interaction with eIF4E and eIF4G 980-1159 . Critical residues for this interaction reside in an internal bulge of Ma5TE, so that their mutation abolished binding to eIF4E + eIF4G 1003-1092 and cap-independent translation. We also developed an in vivo system to test the effect of mutations in eIF4E in Ma5TE-driven cap-independent translation, showing that conserved amino acids in a positively charged RNA-binding motif around amino acid position 228, implicated in eIF4E-eIF4G binding or belonging to the cap-recognition pocket, are essential for cap-independent translation controlled by Ma5TE, and thus for the multiplication of MNSV. © 2016 BSPP AND JOHN WILEY & SONS LTD.
Cap-independent translation ensures mTOR expression and function upon protein synthesis inhibition.

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Marques-Ramos, Ana; Candeias, Marco M; Menezes, Juliane; Lacerda, Rafaela; Willcocks, Margaret; Teixeira, Alexandre; Locker, Nicolas; Romão, Luísa

2017-11-01

The mechanistic/mammalian target of rapamycin (mTOR) is a conserved serine/threonine kinase that integrates cellular signals from the nutrient and energy status to act, namely, on the protein synthesis machinery. While major advances have emerged regarding the regulators and effects of the mTOR signaling pathway, little is known about the regulation of mTOR gene expression. Here, we show that the human mTOR transcript can be translated in a cap-independent manner, and that its 5' untranslated region (UTR) is a highly folded RNA scaffold capable of binding directly to the 40S ribosomal subunit. We further demonstrate that mTOR is able to bypass the cap requirement for translation both in normal and hypoxic conditions. Moreover, our data reveal that the cap-independent translation of mTOR is necessary for its ability to induce cell-cycle progression into S phase. These results suggest a novel regulatory mechanism for mTOR gene expression that integrates the global protein synthesis changes induced by translational inhibitory conditions. © 2017 Marques-Ramos et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.
The nematode eukaryotic translation initiation factor 4E/G complex works with a trans-spliced leader stem-loop to enable efficient translation of trimethylguanosine-capped RNAs.

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Wallace, Adam; Filbin, Megan E; Veo, Bethany; McFarland, Craig; Stepinski, Janusz; Jankowska-Anyszka, Marzena; Darzynkiewicz, Edward; Davis, Richard E

2010-04-01

Eukaryotic mRNA translation begins with recruitment of the 40S ribosome complex to the mRNA 5' end through the eIF4F initiation complex binding to the 5' m(7)G-mRNA cap. Spliced leader (SL) RNA trans splicing adds a trimethylguanosine (TMG) cap and a sequence, the SL, to the 5' end of mRNAs. Efficient translation of TMG-capped mRNAs in nematodes requires the SL sequence. Here we define a core set of nucleotides and a stem-loop within the 22-nucleotide nematode SL that stimulate translation of mRNAs with a TMG cap. The structure and core nucleotides are conserved in other nematode SLs and correspond to regions of SL1 required for early Caenorhabditis elegans development. These SL elements do not facilitate translation of m(7)G-capped RNAs in nematodes or TMG-capped mRNAs in mammalian or plant translation systems. Similar stem-loop structures in phylogenetically diverse SLs are predicted. We show that the nematode eukaryotic translation initiation factor 4E/G (eIF4E/G) complex enables efficient translation of the TMG-SL RNAs in diverse in vitro translation systems. TMG-capped mRNA translation is determined by eIF4E/G interaction with the cap and the SL RNA, although the SL does not increase the affinity of eIF4E/G for capped RNA. These results suggest that the mRNA 5' untranslated region (UTR) can play a positive and novel role in translation initiation through interaction with the eIF4E/G complex in nematodes and raise the issue of whether eIF4E/G-RNA interactions play a role in the translation of other eukaryotic mRNAs.
The 3' untranslated region of tobacco necrosis virus RNA contains a barley yellow dwarf virus-like cap-independent translation element.

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Shen, Ruizhong; Miller, W Allen

2004-05-01

RNAs of many viruses are translated efficiently in the absence of a 5' cap structure. The tobacco necrosis virus (TNV) genome is an uncapped, nonpolyadenylated RNA whose translation mechanism has not been well investigated. Computational analysis predicted a cap-independent translation element (TE) within the 3' untranslated region (3' UTR) of TNV RNA that resembles the TE of barley yellow dwarf virus (BYDV), a luteovirus. Here we report that such a TE does indeed exist in the 3' UTR of TNV strain D. Like the BYDV TE, the TNV TE (i) functions both in vitro and in vivo, (ii) requires additional sequence for cap-independent translation in vivo, (iii) has a similar secondary structure and the conserved sequence CGGAUCCUGGGAAACAGG, (iv) is inactivated by a four-base duplication in this conserved sequence, (v) can function in the 5' UTR, and (vi) when located in its natural 3' location, may form long-distance base pairing with the viral 5' UTR that is conserved and probably required. The TNV TE differs from the BYDV TE by having only three helical domains instead of four. Similar structures were found in all members of the Necrovirus genus of the Tombusviridae family, except satellite tobacco necrosis virus, which harbors a different 3' cap-independent translation domain. The presence of the BYDV-like TE in select genera of different families indicates that phylogenetic distribution of TEs does not follow standard viral taxonomic relationships. We propose a new class of cap-independent TE called BYDV-like TE.
The Nematode Eukaryotic Translation Initiation Factor 4E/G Complex Works with a trans-Spliced Leader Stem-Loop To Enable Efficient Translation of Trimethylguanosine-Capped RNAs ▿ †

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Wallace, Adam; Filbin, Megan E.; Veo, Bethany; McFarland, Craig; Stepinski, Janusz; Jankowska-Anyszka, Marzena; Darzynkiewicz, Edward; Davis, Richard E.

2010-01-01

Eukaryotic mRNA translation begins with recruitment of the 40S ribosome complex to the mRNA 5′ end through the eIF4F initiation complex binding to the 5′ m7G-mRNA cap. Spliced leader (SL) RNA trans splicing adds a trimethylguanosine (TMG) cap and a sequence, the SL, to the 5′ end of mRNAs. Efficient translation of TMG-capped mRNAs in nematodes requires the SL sequence. Here we define a core set of nucleotides and a stem-loop within the 22-nucleotide nematode SL that stimulate translation of mRNAs with a TMG cap. The structure and core nucleotides are conserved in other nematode SLs and correspond to regions of SL1 required for early Caenorhabditis elegans development. These SL elements do not facilitate translation of m7G-capped RNAs in nematodes or TMG-capped mRNAs in mammalian or plant translation systems. Similar stem-loop structures in phylogenetically diverse SLs are predicted. We show that the nematode eukaryotic translation initiation factor 4E/G (eIF4E/G) complex enables efficient translation of the TMG-SL RNAs in diverse in vitro translation systems. TMG-capped mRNA translation is determined by eIF4E/G interaction with the cap and the SL RNA, although the SL does not increase the affinity of eIF4E/G for capped RNA. These results suggest that the mRNA 5′ untranslated region (UTR) can play a positive and novel role in translation initiation through interaction with the eIF4E/G complex in nematodes and raise the issue of whether eIF4E/G-RNA interactions play a role in the translation of other eukaryotic mRNAs. PMID:20154140
The 3′ Untranslated Region of Tobacco Necrosis Virus RNA Contains a Barley Yellow Dwarf Virus-Like Cap-Independent Translation Element

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Shen, Ruizhong; Miller, W. Allen

2004-01-01

RNAs of many viruses are translated efficiently in the absence of a 5′ cap structure. The tobacco necrosis virus (TNV) genome is an uncapped, nonpolyadenylated RNA whose translation mechanism has not been well investigated. Computational analysis predicted a cap-independent translation element (TE) within the 3′ untranslated region (3′ UTR) of TNV RNA that resembles the TE of barley yellow dwarf virus (BYDV), a luteovirus. Here we report that such a TE does indeed exist in the 3′ UTR of TNV strain D. Like the BYDV TE, the TNV TE (i) functions both in vitro and in vivo, (ii) requires additional sequence for cap-independent translation in vivo, (iii) has a similar secondary structure and the conserved sequence CGGAUCCUGGGAAACAGG, (iv) is inactivated by a four-base duplication in this conserved sequence, (v) can function in the 5′ UTR, and (vi) when located in its natural 3′ location, may form long-distance base pairing with the viral 5′ UTR that is conserved and probably required. The TNV TE differs from the BYDV TE by having only three helical domains instead of four. Similar structures were found in all members of the Necrovirus genus of the Tombusviridae family, except satellite tobacco necrosis virus, which harbors a different 3′ cap-independent translation domain. The presence of the BYDV-like TE in select genera of different families indicates that phylogenetic distribution of TEs does not follow standard viral taxonomic relationships. We propose a new class of cap-independent TE called BYDV-like TE. PMID:15078948
HIV-1 transcripts use IRES-initiation under conditions where Cap-dependent translation is restricted by poliovirus 2A protease.

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Raquel Amorim

Full Text Available The 30 different species of mRNAs synthesized during the HIV-1 replication cycle are all capped and polyadenilated. Internal ribosome entry sites have been recognized in the 5' untranslated region of some mRNA species of HIV-1, which would contribute to an alternative mechanism of initiation of mRNA translation. However, the Cap-dependent translation is assumed to be the main mechanism driving the initiation of HIV-1 protein synthesis. In this work, we describe a cell system in which lower to higher levels of transient expression of the poliovirus 2A protease strongly inhibited cellular Cap-dependent translation with no toxic effect to the cells during a 72-hour time frame. In this system, the synthesis of HIV-1 proteins was inhibited in a temporal dose-dependent way. Higher levels of 2A protease expression severely inhibited HIV-1 protein synthesis during the first 24 hours of infection consequently inhibiting viral production and infectivity. Intermediate to lower levels of 2A Protease expression caused the inhibition of viral protein synthesis only during the first 48 hours of viral replication. After this period both protein synthesis and viral release were recovered to the control levels. However, the infectivity of viral progeny was still partially inhibited. These results indicate that two mechanisms of mRNA translation initiation contribute to the synthesis of HIV-1 proteins; during the first 24-48 hours of viral replication HIV-1 protein synthesis is strongly dependent on Cap-initiation, while at later time points IRES-driven translation initiation is sufficient to produce high amounts of viral particles.
Structural plasticity of Barley yellow dwarf virus-like cap-independent translation elements in four genera of plant viral RNAs.

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Wang, Zhaohui; Kraft, Jelena J; Hui, Alice Y; Miller, W Allen

2010-06-20

The 3' untranslated regions (UTRs) of many plant viral RNAs contain cap-independent translation elements (3' CITEs). Among the 3' CITEs, the Barley yellow dwarf virus (BYDV)-like translation elements (BTEs) form a structurally variable and widely distributed group. Viruses in three genera were known to harbor 3' BTEs, defined by the presence of a 17-nt consensus sequence. To understand BTE function, knowledge of phylogenetically conserved structure is essential, yet the secondary structure has been determined only for the BYDV BTE. Here we show that Rose spring dwarf-associated luteovirus, and two viruses in a fourth genus, Umbravirus, contain functional BTEs, despite deviating in the 17nt consensus sequence. Structure probing by selective 2'-hydroxyl acylation and primer extension (SHAPE) revealed conserved and highly variable structures in BTEs in all four genera. We conclude that BTEs tolerate striking evolutionary plasticity in structure, while retaining the ability to stimulate cap-independent translation. Copyright (c) 2010 Elsevier Inc. All rights reserved.
Cap-independent translation mechanism of red clover necrotic mosaic virus RNA2 differs from that of RNA1 and is linked to RNA replication.

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Mizumoto, Hiroyuki; Iwakawa, Hiro-Oki; Kaido, Masanori; Mise, Kazuyuki; Okuno, Tetsuro

2006-04-01

The genome of Red clover necrotic mosaic virus (RCNMV) in the genus Dianthovirus is divided into two RNA molecules of RNA1 and RNA2, which have no cap structure at the 5' end and no poly(A) tail at the 3' end. The 3' untranslated region (3' UTR) of RCNMV RNA1 contains an essential RNA element (3'TE-DR1), which is required for cap-independent translation. In this study, we investigated a cap-independent translational mechanism of RNA2 using a firefly luciferase (Luc) gene expression assay system in cowpea protoplasts and a cell-free lysate (BYL) prepared from evacuolated tobacco BY2 protoplasts. We were unable to detect cis-acting RNA sequences in RNA2 that can replace the function of a cap structure, such as the 3'TE-DR1 of RNA1. However, the uncapped reporter RNA2, RNA2-Luc, in which the Luc open reading frame (ORF) was inserted between the 5' UTR and the movement protein ORF, was effectively translated in the presence of p27 and p88 in protoplasts in which RNA2-Luc was replicated. Time course experiments in protoplasts showed that the translational activity of RNA2-Luc did not reflect the amount of RNA2. Mutations in cis-acting RNA replication elements of RNA2 abolished the cap-independent translational activity of RNA2-Luc, suggesting that the translational activity of RNA2-Luc is coupled to RNA replication. Our results show that the translational mechanism differs between two segmented genomic RNAs of RCNMV. We present a model in which only RNA2 that is generated de novo through the viral RNA replication machinery functions as mRNA for translation.
The utrophin A 5'-UTR drives cap-independent translation exclusively in skeletal muscles of transgenic mice and interacts with eEF1A2.

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Miura, P; Coriati, A; Bélanger, G; De Repentigny, Y; Lee, J; Kothary, R; Holcik, M; Jasmin, B J

2010-04-01

The molecular mechanisms regulating expression of utrophin A are of therapeutic interest since upregulating its expression at the sarcolemma can compensate for the lack of dystrophin in animal models of Duchenne Muscular Dystrophy (DMD). The 5'-UTR of utrophin A has been previously shown to drive cap-independent internal ribosome entry site (IRES)-mediated translation in response to muscle regeneration and glucocorticoid treatment. To determine whether the utrophin A IRES displays tissue specific activity, we generated transgenic mice harboring control (CMV/betaGAL/CAT) or utrophin A 5'-UTR (CMV/betaGAL/UtrA/CAT) bicistronic reporter transgenes. Examination of multiple tissues from two CMV/betaGAL/UtrA/CAT lines revealed that the utrophin A 5'-UTR drives cap-independent translation of the reporter gene exclusively in skeletal muscles and no other examined tissues. This expression pattern suggested that skeletal muscle-specific factors are involved in IRES-mediated translation of utrophin A. We performed RNA-affinity chromatography experiments combined with mass spectrometry to identify trans-factors that bind the utrophin A 5'-UTR and identified eukaryotic elongation factor 1A2 (eEF1A2). UV-crosslinking experiments confirmed the specificity of this interaction. Regions of the utrophin A 5'-UTR that bound eEF1A2 also mediated cap-independent translation in C2C12 muscle cells. Cultured cells lacking eEF1A2 had reduced IRES activity compared with cells overexpressing eEF1A2. Together, these results suggest an important role for eEF1A2 in driving cap-independent translation of utrophin A in skeletal muscle. The trans-factors and signaling pathways driving skeletal-muscle specific IRES-mediated translation of utrophin A could provide unique targets for developing pharmacological-based DMD therapies.
Translation initiation on mRNAs bound by nuclear cap-binding protein complex CBP80/20 requires interaction between CBP80/20-dependent translation initiation factor and eukaryotic translation initiation factor 3g.

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Choe, Junho; Oh, Nara; Park, Sungjin; Lee, Ye Kyung; Song, Ok-Kyu; Locker, Nicolas; Chi, Sung-Gil; Kim, Yoon Ki

2012-05-25

In the cytoplasm of mammalian cells, either cap-binding proteins 80 and 20 (CBP80/20) or eukaryotic translation initiation factor (eIF) 4E can direct the initiation of translation. Although the recruitment of ribosomes to mRNAs during eIF4E-dependent translation (ET) is well characterized, the molecular mechanism for CBP80/20-dependent translation (CT) remains obscure. Here, we show that CBP80/20-dependent translation initiation factor (CTIF), which has been shown to be preferentially involved in CT but not ET, specifically interacts with eIF3g, a component of the eIF3 complex involved in ribosome recruitment. By interacting with eIF3g, CTIF serves as an adaptor protein to bridge the CBP80/20 and the eIF3 complex, leading to efficient ribosome recruitment during CT. Accordingly, down-regulation of CTIF using a small interfering RNA causes a redistribution of CBP80 from polysome fractions to subpolysome fractions, without significant consequence to eIF4E distribution. In addition, down-regulation of eIF3g inhibits the efficiency of nonsense-mediated mRNA decay, which is tightly coupled to CT but not to ET. Moreover, the artificial tethering of CTIF to an intercistronic region of dicistronic mRNA results in translation of the downstream cistron in an eIF3-dependent manner. These findings support the idea that CT mechanistically differs from ET.
Regulation of protein translation initiation in response to ionizing radiation

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Trivigno, Donatella; Bornes, Laura; Huber, Stephan M; Rudner, Justine

2013-01-01

Proliferating tumor cells require continuous protein synthesis. De novo synthesis of most proteins is regulated through cap-dependent translation. Cellular stress such as ionizing radiation (IR) blocks cap-dependent translation resulting in shut-down of global protein translation which saves resources and energy needed for the stress response. At the same time, levels of proteins required for stress response are maintained or even increased. The study aimed to analyze the regulation of signaling pathways controlling protein translation in response to IR and the impact on Mcl-1, an anti-apoptotic and radioprotective protein, which levels rapidly decline upon IR. Protein levels and processing were analyzed by Western blot. The assembly of the translational pre-initiation complex was examined by Immunoprecipitation and pull-down experiments with 7-methyl GTP agarose. To analyze IR-induced cell death, dissipation of the mitochondrial membrane potential and DNA fragmentation were determined by flow cytometry. Protein levels of the different initiation factors were down-regulated using RNA interference approach. IR induced caspase-dependent cleavage of the translational initiation factors eIF4G1, eIF3A, and eIF4B resulting in disassembly of the cap-dependent initiation complex. In addition, DAP5-dependent initiation complex that regulates IRES-dependent translation was disassembled in response to IR. Moreover, IR resulted in dephosphorylation of 4EBP1, an inhibitor of cap-dependent translation upstream of caspase activation. However, knock-down of eIF4G1, eIF4B, DAP5, or 4EBP1 did not affect IR-induced decline of the anti-apoptotic protein Mcl-1. Our data shows that cap-dependent translation is regulated at several levels in response to IR. However, the experiments indicate that IR-induced Mcl-1 decline is not a consequence of translational inhibition in Jurkat cells
Regulation of protein translation initiation in response to ionizing radiation

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Trivigno Donatella

2013-02-01

Full Text Available Abstract Background Proliferating tumor cells require continuous protein synthesis. De novo synthesis of most proteins is regulated through cap-dependent translation. Cellular stress such as ionizing radiation (IR blocks cap-dependent translation resulting in shut-down of global protein translation which saves resources and energy needed for the stress response. At the same time, levels of proteins required for stress response are maintained or even increased. The study aimed to analyze the regulation of signaling pathways controlling protein translation in response to IR and the impact on Mcl-1, an anti-apoptotic and radioprotective protein, which levels rapidly decline upon IR. Methods Protein levels and processing were analyzed by Western blot. The assembly of the translational pre-initiation complex was examined by Immunoprecipitation and pull-down experiments with 7-methyl GTP agarose. To analyze IR-induced cell death, dissipation of the mitochondrial membrane potential and DNA fragmentation were determined by flow cytometry. Protein levels of the different initiation factors were down-regulated using RNA interference approach. Results IR induced caspase-dependent cleavage of the translational initiation factors eIF4G1, eIF3A, and eIF4B resulting in disassembly of the cap-dependent initiation complex. In addition, DAP5-dependent initiation complex that regulates IRES-dependent translation was disassembled in response to IR. Moreover, IR resulted in dephosphorylation of 4EBP1, an inhibitor of cap-dependent translation upstream of caspase activation. However, knock-down of eIF4G1, eIF4B, DAP5, or 4EBP1 did not affect IR-induced decline of the anti-apoptotic protein Mcl-1. Conclusion Our data shows that cap-dependent translation is regulated at several levels in response to IR. However, the experiments indicate that IR-induced Mcl-1 decline is not a consequence of translational inhibition in Jurkat cells.
Opposite responses of rabbit and human globin mRNAs to translational inhibition by cap analogues

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Shakin, S.H.; Liebhaber, S.A.

1987-01-01

The translational efficiency of an mRNA may be determined at the step of translational initiation by the efficiency of its interaction with the cap binding protein complex. To further investigate the role of these interactions in translational control, the authors compare in vitro the relative sensitivities of rabbit and human α- and β-globin mRNAs to translational inhibition by cap analogues. They find that rabbit β-globin mRNA is more resistant to translational inhibition by cap analogues than rabbit α-globin mRNA, while in contrast, human β-globin mRNA is more sensitive to cap analogue inhibition than human α- and β-globin mRNAs is unexpected as direct in vivo and in vitro comparisons of polysome profiles reveal parallel translational handling of the α- and β-globin mRNAs from these two species. This discordance between the relative translational sensitivities of these mRNAs to cap analogues and their relative ribosome loading activities suggests that cap-dependent events may not be rate limiting in steady-state globin translation

Induction of viral, 7-methyl-guanosine cap-independent translation and oncolysis by mitogen-activated protein kinase-interacting kinase-mediated effects on the serine/arginine-rich protein kinase.

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Brown, Michael C; Bryant, Jeffrey D; Dobrikova, Elena Y; Shveygert, Mayya; Bradrick, Shelton S; Chandramohan, Vidyalakshmi; Bigner, Darell D; Gromeier, Matthias

2014-11-01

Protein synthesis, the most energy-consuming process in cells, responds to changing physiologic priorities, e.g., upon mitogen- or stress-induced adaptations signaled through the mitogen-activated protein kinases (MAPKs). The prevailing status of protein synthesis machinery is a viral pathogenesis factor, particularly for plus-strand RNA viruses, where immediate translation of incoming viral RNAs shapes host-virus interactions. In this study, we unraveled signaling pathways centered on the ERK1/2 and p38α MAPK-interacting kinases MNK1/2 and their role in controlling 7-methyl-guanosine (m(7)G) "cap"-independent translation at enterovirus type 1 internal ribosomal entry sites (IRESs). Activation of Raf-MEK-ERK1/2 signals induced viral IRES-mediated translation in a manner dependent on MNK1/2. This effect was not due to MNK's known functions as eukaryotic initiation factor (eIF) 4G binding partner or eIF4E(S209) kinase. Rather, MNK catalytic activity enabled viral IRES-mediated translation/host cell cytotoxicity through negative regulation of the Ser/Arg (SR)-rich protein kinase (SRPK). Our investigations suggest that SRPK activity is a major determinant of type 1 IRES competency, host cell cytotoxicity, and viral proliferation in infected cells. We are targeting unfettered enterovirus IRES activity in cancer with PVSRIPO, the type 1 live-attenuated poliovirus (PV) (Sabin) vaccine containing a human rhinovirus type 2 (HRV2) IRES. A phase I clinical trial of PVSRIPO with intratumoral inoculation in patients with recurrent glioblastoma (GBM) is showing early promise. Viral translation proficiency in infected GBM cells is a core requirement for the antineoplastic efficacy of PVSRIPO. Therefore, it is critically important to understand the mechanisms controlling viral cap-independent translation in infected host cells. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Modulation of translation-initiation in CHO-K1 cells by rapamycin-induced heterodimerization of engineered eIF4G fusion proteins.

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Schlatter, Stefan; Senn, Claudia; Fussenegger, Martin

2003-07-20

Translation-initiation is a predominant checkpoint in mammalian cells which controls protein synthesis and fine-tunes the flow of information from gene to protein. In eukaryotes, translation-initiation is typically initiated at a 7-methyl-guanylic acid cap posttranscriptionally linked to the 5' end of mRNAs. Alternative cap-independent translation-initiation involves 5' untranslated regions (UTR) known as internal ribosome entry sites, which adopt a particular secondary structure. Translation-initiating ribosome assembly at cap or IRES elements is mediated by a multiprotein complex of which the initiation factor 4F (eIF4F) consisting of eIF4A (helicase), eIF4E (cap-binding protein), and eIF4G is a major constituent. eIF4G is a key target of picornaviral protease 2A, which cleaves this initiation factor into eIF4G(Delta) and (Delta)eIF4G to redirect the cellular translation machinery exclusively to its own IRES-containing transcripts. We have designed a novel translation control system (TCS) for conditional as well as adjustable translation of cap- and IRES-dependent transgene mRNAs in mammalian cells. eIF4G(Delta) and (Delta)eIF4G were fused C- and N-terminally to the FK506-binding protein (FKBP) and the FKBP-rapamycin-binding domain (FRB) of the human FKBP-rapamycin-associated protein (FRAP), respectively. Rapamycin-induced heterodimerization of eIF4G(Delta)-FKBP and FRB-(Delta)eIF4G fusion proteins reconstituted a functional chimeric elongation factor 4G in a dose-dependent manner. Rigorous quantitative expression analysis of cap- and IRES-dependent SEAP- (human placental secreted alkaline phosphatase) and luc- (Photinus pyralis luciferase) encoding reporter constructs confirmed adjustable translation control and revealed increased production of desired proteins in response to dimerization-induced heterologous eIF4G in Chinese hamster ovary (CHO-K1) cells. Copyright 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 210-225, 2003.
4EGI-1 represses cap-dependent translation and regulates genome-wide translation in malignant pleural mesothelioma.

Science.gov (United States)

De, Arpita; Jacobson, Blake A; Peterson, Mark S; Jay-Dixon, Joe; Kratzke, Marian G; Sadiq, Ahad A; Patel, Manish R; Kratzke, Robert A

2018-04-01

Deregulation of cap-dependent translation has been implicated in the malignant transformation of numerous human tissues. 4EGI-1, a novel small-molecule inhibitor of cap-dependent translation, disrupts formation of the eukaryotic initiation factor 4F (eIF4F) complex. The effects of 4EGI-1-mediated inhibition of translation initiation in malignant pleural mesothelioma (MPM) were examined. 4EGI-1 preferentially inhibited cell viability and induced apoptosis in MPM cells compared to normal mesothelial (LP9) cells. This effect was associated with hypophosphorylation of 4E-binding protein 1 (4E-BP1) and decreased protein levels of the cancer-related genes, c-myc and osteopontin. 4EGI-1 showed enhanced cytotoxicity in combination with pemetrexed or gemcitabine. Translatome-wide polysome microarray analysis revealed a large cohort of genes that were translationally regulated upon treatment with 4EGI-1. The 4EGI-1-regulated translatome was negatively correlated to a previously published translatome regulated by eIF4E overexpression in human mammary epithelial cells, which is in agreement with the notion that 4EGI-1 inhibits the eIF4F complex. These data indicate that inhibition of the eIF4F complex by 4EGI-1 or similar translation inhibitors could be a strategy for treating mesothelioma. Genome wide translational profiling identified a large cohort of promising target genes that should be further evaluated for their potential significance in the treatment of MPM.
Alternate capping mechanisms for transcription of spring viremia of carp virus: evidence for independent mRNA initiation.

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Gupta, K C; Roy, P

1980-01-01

Two alternate mechanisms of mRNA capping for spring viremia of carp virus have been observed. Under normal reaction conditions, a ppG residue of the capping GTP is transferred to a pA moiety of the 5' termini of mRNA transcripts. However, in reaction conditions where GppNHp is used instead of GTP, an alternate capping mechanism occurs whereby a pG residue of the capping GTP is transferred to a ppA moiety of the transcripts. The first mechanism is identical to that described previously for vesicular stomatitis virus (G. Abraham, D. P. Rhodes, and A. K. Banerjee, Nature [London] 255:37-40, 1975; A. K. Banerjee, S. A. Moyer, and D. P. Rhodes, Virology 61:547-558, 1974), and thus appears to be a conserved function during the evolution of rhabdoviruses. The alternate mechanism of capping indicates not only that capping can take place by two procedures, but also that the substrate termini have di- or triphosphate 5' ends, indicating that they are probably independently initiated. An analog of ATP, AppNHp, has been found to completely inhibit the initiation of transcription by spring viremia of carp virus, suggesting that a cleavage between the beta and gamma phosphates of ATP is essential for the initiation of transcription. However, in the presence of GppNHp, uncapped (ppAp and pppAp), capped (GpppAp), and capped methylated (m7GpppAmpAp and GpppAmpAp) transcripts are detected. Size analyses of oligodeoxythymidylic acid-cellulose-bound transcripts resolved by formamide gel electrophoresis demonstrated that full-size mRNA transcripts are synthesized as well as larger RNA species. The presence of GppNHp and S-adenosylhomocysteine in reaction mixtures did not have any effect on the type of unmethylated transcription products. Our results favor a transcription model postulated previously (D. H. L. Bishop, in H. Fraenkel-Conrat and R. R. Wagner, ed., Comprehensive Virology, vol. 10, Plenum Press, New York, 1977; D. H. L. Bishop and A. Flamand, in D. C. Burke and W. C. Russell
A proposed vestigial translation initiation motif in VP1 of hepatitis A virus.

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Kang, Jeong-Ah; Funkhouser, Ann W

2002-07-01

The internal ribosome entry site (IRES) of picornaviruses has a 3' polypyrimidine tract (PPT) 16-24 bases upstream of an AUG triplet (PPT/AUG motif). This motif is critical in determining the efficiency of cap-independent translation. HAV has a conserved PPT/AUG motif consisting of a nine base sequence (AGGUUUUUC) 23 bases upstream of the preferred AUG start codon. This HAV-specific PPT/AUG motif is repeated and conserved in VP1 of HAV, but not of other picornaviruses. We proposed that the PPT/AUG motif in the open reading frame initiated translation and/or had an impact on the life cycle of the virus. In vitro translation of mutant bicistronic mRNAs and growth in cell culture of mutant viruses provided no evidence that the VP1 PPT/AUG motif had any impact on either translation or growth. HAV differs from other picornaviruses in its inefficient growth in cell culture. Since the HAV-specific PPT/AUG motif is found in only 1 in 300,000 reported viral sequences outside the hepatovirus genus, this motif may be a vestigial translation initiation element and may have played a role in determining the unusual phenotype of HAV.
Switch from cap- to factorless IRES-dependent 0 and +1 frame translation during cellular stress and dicistrovirus infection.

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Qing S Wang

Full Text Available Internal ribosome entry sites (IRES are utilized by a subset of cellular and viral mRNAs to initiate translation during cellular stress and virus infection when canonical cap-dependent translation is compromised. The intergenic region (IGR IRES of the Dicistroviridae uses a streamlined mechanism in which it can directly recruit the ribosome in the absence of initiation factors and initiates translation using a non-AUG codon. A subset of IGR IRESs including that from the honey bee viruses can also direct translation of an overlapping +1 frame gene. In this study, we systematically examined cellular conditions that lead to IGR IRES-mediated 0 and +1 frame translation in Drosophila S2 cells. Towards this, a novel bicistronic reporter that exploits the 2A "stop-go" peptide was developed to allow the detection of IRES-mediated translation in vivo. Both 0 and +1 frame translation by the IGR IRES are stimulated under a number of cellular stresses and in S2 cells infected by cricket paralysis virus, demonstrating a switch from cap-dependent to IRES-dependent translation. The regulation of the IGR IRES mechanism ensures that both 0 frame viral structural proteins and +1 frame ORFx protein are optimally expressed during virus infection.
Inhibition of Ribosome Recruitment Induces Stress Granule Formation Independently of Eukaryotic Initiation Factor 2α Phosphorylation

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Mazroui, Rachid; Sukarieh, Rami; Bordeleau, Marie-Eve; Kaufman, Randal J.; Northcote, Peter; Tanaka, Junichi; Gallouzi, Imed

2006-01-01

Cytoplasmic aggregates known as stress granules (SGs) arise as a consequence of cellular stress and contain stalled translation preinitiation complexes. These foci are thought to serve as sites of mRNA storage or triage during the cell stress response. SG formation has been shown to require induction of eukaryotic initiation factor (eIF)2α phosphorylation. Herein, we investigate the potential role of other initiation factors in this process and demonstrate that interfering with eIF4A activity, an RNA helicase required for the ribosome recruitment phase of translation initiation, induces SG formation and that this event is not dependent on eIF2α phosphorylation. We also show that inhibition of eIF4A activity does not impair the ability of eIF2α to be phosphorylated under stress conditions. Furthermore, we observed SG assembly upon inhibition of cap-dependent translation after poliovirus infection. We propose that SG modeling can occur via both eIF2α phosphorylation-dependent and -independent pathways that target translation initiation. PMID:16870703
Inhibition of ribosome recruitment induces stress granule formation independently of eukaryotic initiation factor 2alpha phosphorylation.

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Mazroui, Rachid; Sukarieh, Rami; Bordeleau, Marie-Eve; Kaufman, Randal J; Northcote, Peter; Tanaka, Junichi; Gallouzi, Imed; Pelletier, Jerry

2006-10-01

Cytoplasmic aggregates known as stress granules (SGs) arise as a consequence of cellular stress and contain stalled translation preinitiation complexes. These foci are thought to serve as sites of mRNA storage or triage during the cell stress response. SG formation has been shown to require induction of eukaryotic initiation factor (eIF)2alpha phosphorylation. Herein, we investigate the potential role of other initiation factors in this process and demonstrate that interfering with eIF4A activity, an RNA helicase required for the ribosome recruitment phase of translation initiation, induces SG formation and that this event is not dependent on eIF2alpha phosphorylation. We also show that inhibition of eIF4A activity does not impair the ability of eIF2alpha to be phosphorylated under stress conditions. Furthermore, we observed SG assembly upon inhibition of cap-dependent translation after poliovirus infection. We propose that SG modeling can occur via both eIF2alpha phosphorylation-dependent and -independent pathways that target translation initiation.
Human cytomegalovirus TRS1 protein associates with the 7-methylguanosine mRNA cap and facilitates translation.

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Ziehr, Benjamin; Lenarcic, Erik; Vincent, Heather A; Cecil, Chad; Garcia, Benjamin; Shenk, Thomas; Moorman, Nathaniel J

2015-06-01

Viruses rely on the host translation machinery for the synthesis of viral proteins. Human cells have evolved sensors that recognize viral RNAs and inhibit mRNA translation in order to limit virus replication. Understanding how viruses manipulate the host translation machinery to gain access to ribosomes and disable the antiviral response is therefore a critical aspect of the host/pathogen interface. In this study, we used a proteomics approach to identify human cytomegalovirus (HCMV) proteins that might contribute to viral mRNA translation. The HCMV TRS1 protein (pTRS1) associated with the 7-methylguanosine mRNA cap, increased the total level of protein synthesis, and colocalized with mRNAs undergoing translation initiation during infection. pTRS1 stimulated translation of a nonviral reporter gene and increased the translation of a reporter containing an HCMV 5' untranslated region (5'UTR) to a greater extent. The preferential effect of pTRS1 on translation of an mRNA containing a viral 5'UTR required the pTRS1 RNA and double-stranded RNA-dependent protein kinase (PKR)-binding domains, and was likely the result of PKR inhibition. However, pTRS1 also stimulated the total level of protein synthesis and translation directed by an HCMV 5'UTR in cells lacking PKR. Thus our results demonstrate that pTRS1 stimulates translation through both PKR-dependent and PKR-independent mechanisms. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Promotion of Viral IRES-Mediated Translation Initiation under Mild Hypothermia.

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Maria Licursi

Full Text Available Internal ribosome entry site (IRES-mediated translation is an essential replication step for certain viruses. As IRES-mediated translation is regulated differently from cap-dependent translation under various cellular conditions, we sought to investigate whether temperature influences efficiency of viral IRES-mediated translation initiation by using bicistronic reporter constructs containing an IRES element of encephalomyocarditis virus (EMCV, foot-and-mouth disease virus (FMDV, hepatitis C virus (HCV, human rhinovirus (HRV or poliovirus (PV. Under mild hypothermic conditions (30 and 35°C, we observed increases in the efficiency of translation initiation by HCV and HRV IRES elements compared to translation initiation at 37°C. The promotion of HRV IRES activity was observed as early as 2 hours after exposure to mild hypothermia. We also confirmed the promotion of translation initiation by HRV IRES under mild hypothermia in multiple cell lines. The expression levels and locations of polypyrimidine tract-binding protein (PTB and upstream of N-Ras (unr, the IRES trans-acting factors (ITAFs of HCV and HRV IRES elements, were not modulated by the temperature shift from 37°C to 30°C. Taken together, this study demonstrates that efficiency of translation initiation by some viral IRES elements is temperature dependent.
5'-3' RNA-RNA interaction facilitates cap- and poly(A) tail-independent translation of tomato bushy stunt virus mrna: a potential common mechanism for tombusviridae.

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Fabian, Marc R; White, K Andrew

2004-07-09

Tomato bushy stunt virus (TBSV) is the prototypical member of the genus Tombusvirus in the family Tombusviridae. The (+)-strand RNA genome of TBSV lacks both a 5' cap and a 3' poly(A) tail and instead contains a 3'-terminal RNA sequence that acts as a cap-independent translational enhancer (3' CITE). In this study, we have determined the RNA secondary structure of the translation-specific central segment of the 3' CITE, termed region 3.5 (R3.5). MFOLD structural modeling combined with solution structure mapping and comparative sequence analysis indicate that R3.5 adopts a branched structure that contains three major helices. Deletion and substitution studies revealed that two of these extended stem-loop (SL) structures are essential for 3' CITE activity in vivo. In particular, the terminal loop of one of these SLs, SL-B, was found to be critical for translation. Compensatory mutational analysis showed that SL-B functions by base pairing with another SL, SL3, in the 5' untranslated region of the TBSV genome. Thus, efficient translation of TBSV mRNA in vivo requires a 5'-3' RNA-RNA interaction that effectively circularizes the message. Similar types of interactions are also predicted to occur in TBSV subgenomic mRNAs between their 5' untranslated regions and the 3' CITE, and both genomic and subgenomic 5'-3' interactions are well conserved in all members of the genus Tombusvirus. In addition, a survey of other genera in Tombusviridae revealed the potential for similar 5'-3' RNA-RNA-based interactions in their viral mRNAs, suggesting that this mechanism extends throughout this large virus family.
MCT-1 protein interacts with the cap complex and modulates messenger RNA translational profiles

DEFF Research Database (Denmark)

Reinert, Line; Shi, B; Nandi, S

2006-01-01

MCT-1 is an oncogene that was initially identified in a human T cell lymphoma and has been shown to induce cell proliferation as well as activate survival-related pathways. MCT-1 contains the PUA domain, a recently described RNA-binding domain that is found in several tRNA and rRNA modification...... enzymes. Here, we established that MCT-1 protein interacts with the cap complex through its PUA domain and recruits the density-regulated protein (DENR/DRP), containing the SUI1 translation initiation domain. Through the use of microarray analysis on polysome-associated mRNAs, we showed that up......-regulation of MCT-1 was able to modulate the translation profiles of BCL2L2, TFDP1, MRE11A, cyclin D1, and E2F1 mRNAs, despite equivalent levels of mRNAs in the cytoplasm. Our data establish a role for MCT-1 in translational regulation, and support a linkage between translational control and oncogenesis....
Deregulation of cap-dependent mRNA translation increases tumour radiosensitivity through reduction of the hypoxic fraction

NARCIS (Netherlands)

Rouschop, K.M.; Dubois, L.; Schaaf, M.B.; Beucken, T. van den; Lieuwes, N.; Keulers, T.G.; Savelkouls, K.G.; Bussink, J.; Kogel, A.J. van der; Koritzinsky, M.; Wouters, B.G.

2011-01-01

BACKGROUND AND PURPOSE: Tumour hypoxia is an important limiting factor in the successful treatment of cancer. Adaptation to hypoxia includes inhibition of mTOR, causing scavenging of eukaryotic initiation factor 4E (eIF4E), the rate-limiting factor for cap-dependent translation. The aim of this
Back to basics: the untreated rabbit reticulocyte lysate as a competitive system to recapitulate cap/poly(A) synergy and the selective advantage of IRES-driven translation.

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Soto Rifo, Ricardo; Ricci, Emiliano P; Décimo, Didier; Moncorgé, Olivier; Ohlmann, Théophile

2007-01-01

Translation of most eukaryotic mRNAs involves the synergistic action between the 5' cap structure and the 3' poly(A) tail at the initiation step. The poly(A) tail has also been shown to stimulate translation of picornavirus internal ribosome entry sites (IRES)-directed translation. These effects have been attributed principally to interactions between eIF4G and poly(A)-binding protein (PABP) but also to the participation of PABP in other steps during translation initiation. As the rabbit reticulocyte lysate (RRL) does not recapitulate this cap/poly(A) synergy, several systems based on cellular cell-free extracts have been developed to study the effects of poly(A) tail in vitro but they generally exhibit low translational efficiency. Here, we describe that the non-nuclease-treated RRL (untreated RRL) is able to recapitulate the effects of poly(A) tail on translation in vitro. In this system, translation of a capped/polyadenylated RNA was specifically inhibited by either Paip2 or poly(rA), whereas translation directed by HCV IRES remained unaffected. Moreover, cleavage of eIF4G by FMDV L protease strongly stimulated translation directed by the EMCV IRES, thus recapitulating the competitive advantage that the proteolytic processing of eIF4G confers to IRES-driven RNAs.
Cap-proximal nucleotides via differential eIF4E binding and alternative promoter usage mediate translational response to energy stress.

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Tamarkin-Ben-Harush, Ana; Vasseur, Jean-Jacques; Debart, Françoise; Ulitsky, Igor; Dikstein, Rivka

2017-02-08

Transcription start-site (TSS) selection and alternative promoter (AP) usage contribute to gene expression complexity but little is known about their impact on translation. Here we performed TSS mapping of the translatome following energy stress. Assessing the contribution of cap-proximal TSS nucleotides, we found dramatic effect on translation only upon stress. As eIF4E levels were reduced, we determined its binding to capped-RNAs with different initiating nucleotides and found the lowest affinity to 5'cytidine in correlation with the translational stress-response. In addition, the number of differentially translated APs was elevated following stress. These include novel glucose starvation-induced downstream transcripts for the translation regulators eIF4A and Pabp, which are also translationally-induced despite general translational inhibition. The resultant eIF4A protein is N-terminally truncated and acts as eIF4A inhibitor. The induced Pabp isoform has shorter 5'UTR removing an auto-inhibitory element. Our findings uncovered several levels of coordination of transcription and translation responses to energy stress.
Inhibition of translation by 7-methyl guanosine (m7G) nucleotide cap analogs with derivatized 5'-monophosphates

International Nuclear Information System (INIS)

Tahara, S.M.; Darzynkiewicz, E.; Ekiel, I.

1986-01-01

Recognition of the 5'-m 7 GpppN (cap) structure of eukaryote mRNA is an important step of translation initiation as shown by the potent inhibitory effect of m 7 G nucleotides on this process. A comparison of cap analogs as competitive inhibitors of initiation has allowed the authors to map probable protein-ligand contact points between the cap and cognate cap binding proteins (CBPs). Recently, several new derivatives of m 7 GMP (1) with modified phosphates were synthesized: m 7 G 5'-phosphite (2), m 7 G 5'-phosphoramidate (3), m 7 G 5'-methylphosphonate (4), and m 7 G 5'-phosphate-O-methyl ester (5). In addition, 7,8-dimethyl GMP (6) and 7-methyl 8-amino GMP (7) were synthesized. 6 and7 are primarily syn and anti respectively, relative to the glycosidic bond as shown by solution NMR studies. Inhibition by analogs on total translation in reticulocyte lysate and binding of mRNA to rabbit reticulocyte ribosomes was found to be: 1 = 3 > 5 > 4 > 2. The inhibitory activity of 3 was unexpected since it is isosteric with 4, however it suggested that electron configuration and/or the ability to form a hydrogen bond between protein and the phosphate moiety might be important for ligand binding. 7 was more inhibitory than 6. The latter two are isosteric therefore differences in electron delocalization and/or syn-anti conformation are likely to be the reason(s) for the observed difference
Regulation of cap-dependent translation initiation in the early stage porcine parthenotes

Czech Academy of Sciences Publication Activity Database

Šušor, Andrej; Jelínková, Lucie; Karabínová, Pavla; Torner, H.; Tomek, W.; Kovářová, Hana; Kubelka, Michal

2008-01-01

Roč. 75, č. 12 (2008), s. 1716-1725 ISSN 1040-452X R&D Projects: GA ČR GA524/04/0104; GA ČR GA524/07/1087 Institutional research plan: CEZ:AV0Z50450515 Keywords : meiosis * translation initiation * porcine parthenotes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.287, year: 2008
HIV-1 Replication and the Cellular Eukaryotic Translation Apparatus

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Santiago Guerrero

2015-01-01

Full Text Available Eukaryotic translation is a complex process composed of three main steps: initiation, elongation, and termination. During infections by RNA- and DNA-viruses, the eukaryotic translation machinery is used to assure optimal viral protein synthesis. Human immunodeficiency virus type I (HIV-1 uses several non-canonical pathways to translate its own proteins, such as leaky scanning, frameshifting, shunt, and cap-independent mechanisms. Moreover, HIV-1 modulates the host translation machinery by targeting key translation factors and overcomes different cellular obstacles that affect protein translation. In this review, we describe how HIV-1 proteins target several components of the eukaryotic translation machinery, which consequently improves viral translation and replication.
The triplet repeats of the Sin Nombre hantavirus 5' untranslated region are sufficient in cis for nucleocapsid-mediated translation initiation.

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Mir, Mohammad A; Panganiban, Antonito T

2010-09-01

Hantavirus nucleocapsid protein (N) can replace the cellular cap-binding complex, eukaryotic initiation factor 4F (eIF4F), to mediate translation initiation. Although N can augment translation initiation of nonviral mRNA, initiation of viral mRNA by N is superior. All members of the Bunyaviridae family, including the species of the hantavirus genus, express either three or four primary mRNAs from their tripartite negative-sense genomes. The 5' ends of the mRNAs contain nonviral heterologous oligonucleotides that originate from endonucleolytic cleavage of cellular mRNA during the process of cap snatching. In the hantaviruses these caps terminate with a 3' G residue followed by nucleotides arising from the viral template. Further, the 5' untranslated region (UTR) of viral mRNA uniformly contains, near the 5' end, either two or three copies of the triplet repeat sequence, UAGUAG or UAGUAGUAG. Through analysis of a panel of mutants with mutations in the viral UTR, we found that the sequence GUAGUAG is sufficient for preferential N-mediated translation initiation and for high-affinity binding of N to the UTR. This heptanucleotide sequence is present in viral mRNA containing either two or three copies of the triplet repeat.
Exaggerated Cap-Dependent Translation as a Mechanism for Corticostriatal Dysfunction in Fragile X Syndrome Model Mice

Science.gov (United States)

2017-11-01

AWARD NUMBER: W81XWH-15-1-0361 TITLE: “Exaggerated Cap-Dependent Translation as a Mechanism for Corticostriatal Dysfunction in Fragile X...Annual 3. DATES COVERED 19Oct2016 - 18Oct2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER “Exaggerated Cap-Dependent Translation as a Mechanism for... translation inhibitors. Our specific tasks are centered on a proteomic study of FXS striatal synapses by using a transgenic mouse model that allows to

Functional 5' UTR mRNA structures in eukaryotic translation regulation and how to find them.

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Leppek, Kathrin; Das, Rhiju; Barna, Maria

2018-03-01

RNA molecules can fold into intricate shapes that can provide an additional layer of control of gene expression beyond that of their sequence. In this Review, we discuss the current mechanistic understanding of structures in 5' untranslated regions (UTRs) of eukaryotic mRNAs and the emerging methodologies used to explore them. These structures may regulate cap-dependent translation initiation through helicase-mediated remodelling of RNA structures and higher-order RNA interactions, as well as cap-independent translation initiation through internal ribosome entry sites (IRESs), mRNA modifications and other specialized translation pathways. We discuss known 5' UTR RNA structures and how new structure probing technologies coupled with prospective validation, particularly compensatory mutagenesis, are likely to identify classes of structured RNA elements that shape post-transcriptional control of gene expression and the development of multicellular organisms.
A Point Mutation in the Exon Junction Complex Factor Y14 Disrupts Its Function in mRNA Cap Binding and Translation Enhancement*

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Chuang, Tzu-Wei; Lee, Kuo-Ming; Lou, Yuan-Chao; Lu, Chia-Chen; Tarn, Woan-Yuh

2016-01-01

Eukaryotic mRNA biogenesis involves a series of interconnected steps mediated by RNA-binding proteins. The exon junction complex core protein Y14 is required for nonsense-mediated mRNA decay (NMD) and promotes translation. Moreover, Y14 binds the cap structure of mRNAs and inhibits the activity of the decapping enzyme Dcp2. In this report, we show that an evolutionarily conserved tryptophan residue (Trp-73) of Y14 is critical for its binding to the mRNA cap structure. A Trp-73 mutant (W73V) bound weakly to mRNAs and failed to protect them from degradation. However, this mutant could still interact with the NMD and mRNA degradation factors and retained partial NMD activity. In addition, we found that the W73V mutant could not interact with translation initiation factors. Overexpression of W73V suppressed reporter mRNA translation in vitro and in vivo and reduced the level of a set of nascent proteins. These results reveal a residue of Y14 that confers cap-binding activity and is essential for Y14-mediated enhancement of translation. Finally, we demonstrated that Y14 may selectively and differentially modulate protein biosynthesis. PMID:26887951
A Point Mutation in the Exon Junction Complex Factor Y14 Disrupts Its Function in mRNA Cap Binding and Translation Enhancement.

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Chuang, Tzu-Wei; Lee, Kuo-Ming; Lou, Yuan-Chao; Lu, Chia-Chen; Tarn, Woan-Yuh

2016-04-15

Eukaryotic mRNA biogenesis involves a series of interconnected steps mediated by RNA-binding proteins. The exon junction complex core protein Y14 is required for nonsense-mediated mRNA decay (NMD) and promotes translation. Moreover, Y14 binds the cap structure of mRNAs and inhibits the activity of the decapping enzyme Dcp2. In this report, we show that an evolutionarily conserved tryptophan residue (Trp-73) of Y14 is critical for its binding to the mRNA cap structure. A Trp-73 mutant (W73V) bound weakly to mRNAs and failed to protect them from degradation. However, this mutant could still interact with the NMD and mRNA degradation factors and retained partial NMD activity. In addition, we found that the W73V mutant could not interact with translation initiation factors. Overexpression of W73V suppressed reporter mRNA translation in vitro and in vivo and reduced the level of a set of nascent proteins. These results reveal a residue of Y14 that confers cap-binding activity and is essential for Y14-mediated enhancement of translation. Finally, we demonstrated that Y14 may selectively and differentially modulate protein biosynthesis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Evolutionary Conservation and Diversification of the Translation Initiation Apparatus in Trypanosomatids

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Alexandra Zinoviev

2012-01-01

Full Text Available Trypanosomatids are ancient eukaryotic parasites that migrate between insect vectors and mammalian hosts, causing a range of diseases in humans and domestic animals. Trypanosomatids feature a multitude of unusual molecular features, including polycistronic transcription and subsequent processing by trans-splicing and polyadenylation. Regulation of protein coding genes is posttranscriptional and thus, translation regulation is fundamental for activating the developmental program of gene expression. The spliced-leader RNA is attached to all mRNAs. It contains an unusual hypermethylated cap-4 structure in its 5 end. The cap-binding complex, eIF4F, has gone through evolutionary changes in accordance with the requirement to bind cap-4. The eIF4F components in trypanosomatids are highly diverged from their orthologs in higher eukaryotes, and their potential functions are discussed. The cap-binding activity in all eukaryotes is a target for regulation and plays a similar role in trypanosomatids. Recent studies revealed a novel eIF4E-interacting protein, involved in directing stage-specific and stress-induced translation pathways. Translation regulation during stress also follows unusual regulatory cues, as the increased translation of Hsp83 following heat stress is driven by a defined element in the 3 UTR, unlike higher eukaryotes. Overall, the environmental switches experienced by trypanosomatids during their life cycle seem to affect their translational machinery in unique ways.
The Triticum Mosaic Virus 5' Leader Binds to Both eIF4G and eIFiso4G for Translation.

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Robyn Roberts

Full Text Available We recently identified a remarkably strong (739 nt-long IRES-like element in the 5' untranslated region (UTR of Triticum mosaic virus (TriMV, Potyviridae. Here, we define the components of the cap-binding translation initiation complex that are required for TriMV translation. Using bio-layer interferometry and affinity capture of the native translation apparatus, we reveal that the viral translation element has a ten-fold greater affinity for the large subunit eIF4G/eIFiso4G than to the cap binding protein eIF4E/eIFiso4E. This data supports a translation mechanism that is largely dependent on eIF4G and its isoform. The binding of both scaffold isoforms requires an eight base-pair-long hairpin structure located 270 nucleotides upstream of the translation initiation site, which we have previously shown to be crucial for IRES activity. Despite a weak binding affinity to the mRNA, eIFiso4G alone or in combination with eIFiso4E supports TriMV translation in a cap-binding factor-depleted wheat germ extract. Notably, TriMV 5' UTR-mediated translation is dependent upon eIF4A helicase activity, as the addition of the eIF4A inhibitor hippuristanol inhibits 5' UTR-mediated translation. This inhibition is reversible with the addition of recombinant wheat eIF4A. These results and previous observations demonstrate a key role of eIF4G and eIF4A in this unique mechanism of cap-independent-translation. This work provides new insights into the lesser studied translation mechanisms of plant virus-mediated internal translation initiation.
Functional 5′ UTR mRNA structures in eukaryotic translation regulation and how to find them

Science.gov (United States)

Leppek, Kathrin; Das, Rhiju; Barna, Maria

2017-01-01

RNA molecules can fold into intricate shapes that can provide an additional layer of control of gene expression beyond that of their sequence. In this Review, we discuss the current mechanistic understanding of structures in 5′ untranslated regions (UTRs) of eukaryotic mRNAs and the emerging methodologies used to explore them. These structures may regulate cap-dependent translation initiation through helicase-mediated remodelling of RNA structures and higher-order RNA interactions, as well as cap-independent translation initiation through internal ribosome entry sites (IRESs), mRNA modifications and other specialized translation pathways. We discuss known 5′ UTR RNA structures and how new structure probing technologies coupled with prospective validation, particularly compensatory mutagenesis, are likely to identify classes of structured RNA elements that shape post-transcriptional control of gene expression and the development of multicellular organisms. PMID:29165424
The 5'-poly(A leader of poxvirus mRNA confers a translational advantage that can be achieved in cells with impaired cap-dependent translation.

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Pragyesh Dhungel

2017-08-01

Full Text Available The poly(A leader at the 5'-untranslated region (5'-UTR is an unusually striking feature of all poxvirus mRNAs transcribed after viral DNA replication (post-replicative mRNAs. These poly(A leaders are non-templated and of heterogeneous lengths; and their function during poxvirus infection remains a long-standing question. Here, we discovered that a 5'-poly(A leader conferred a selective translational advantage to mRNA in poxvirus-infected cells. A constitutive and uninterrupted 5'-poly(A leader with 12 residues was optimal. Because the most frequent lengths of the 5'-poly(A leaders are 8-12 residues, the result suggests that the poly(A leader has been evolutionarily optimized to boost poxvirus protein production. A 5'-poly(A leader also could increase protein production in the bacteriophage T7 promoter-based expression system of vaccinia virus, the prototypic member of poxviruses. Interestingly, although vaccinia virus post-replicative mRNAs do have 5'- methylated guanosine caps and can use cap-dependent translation, in vaccinia virus-infected cells, mRNA with a 5'-poly(A leader could also be efficiently translated in cells with impaired cap-dependent translation. However, the translation was not mediated through an internal ribosome entry site (IRES. These results point to a fundamental mechanism poxvirus uses to efficiently translate its post-replicative mRNAs.
Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms.

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Kahvejian, Avak; Svitkin, Yuri V; Sukarieh, Rami; M'Boutchou, Marie-Noël; Sonenberg, Nahum

2005-01-01

Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5'-end of the mRNA to promote the recruitment of the ribosome. Although the 3' poly(A) tail of eukaryotic mRNAs and its major bound protein, the poly(A)-binding protein (PABP), have been studied extensively, their mechanism of action in translation is not well understood and is confounded by differences between in vivo and in vitro systems. Here, we provide direct evidence for the involvement of PABP in key steps of the translation initiation pathway. Using a new technique to deplete PABP from mammalian cell extracts, we show that extracts lacking PABP exhibit dramatically reduced rates of translation, reduced efficiency of 48S and 80S ribosome initiation complex formation, and impaired interaction of eIF4E with the mRNA cap structure. Supplementing PABP-depleted extracts with wild-type PABP completely rectified these deficiencies, whereas a mutant of PABP, M161A, which is incapable of interacting with eIF4G, failed to restore translation. In addition, a stronger inhibition (approximately twofold) of 80S as compared to 48S ribosome complex formation (approximately 65% vs. approximately 35%, respectively) by PABP depletion suggests that PABP plays a direct role in 60S subunit joining. PABP can thus be considered a canonical translation initiation factor, integral to initiation complex formation at the 5'-end of mRNA.
Identifying intrinsic and extrinsic determinants that regulate internal initiation of translation mediated by the FMR1 5' leader

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Timmerman Stephanie

2008-10-01

Full Text Available Abstract Background Regulating synthesis of the Fragile X gene (FMR1 product, FMRP alters neural plasticity potentially through its role in the microRNA pathway. Cap-dependent translation of the FMR1 mRNA, a process requiring ribosomal scanning through the 5' leader, is likely impeded by the extensive secondary structure generated by the high guanosine/cytosine nucleotide content including the CGG triplet nucleotide repeats in the 5' leader. An alternative mechanism to initiate translation – internal initiation often utilizes secondary structure to recruit the translational machinery. Consequently, studies were undertaken to confirm and extend a previous observation that the FMR1 5' leader contains an internal ribosomal entry site (IRES. Results Cellular transfection of a dicistronic DNA construct containing the FMR1 5' leader inserted into the intercistronic region yielded significant translation of the second cistron, but the FMR1 5' leader was also found to contain a cryptic promoter possibly confounding interpretation of these results. However, transfection of dicistronic and monocistronic RNA ex vivo or in vitro confirmed that the FMR1 5' leader contains an IRES. Moreover, inhibiting cap-dependent translation ex vivo did not affect the expression level of endogenous FMRP indicating a role for IRES-dependent translation of FMR1 mRNA. Analysis of the FMR1 5' leader revealed that the CGG repeats and the 5' end of the leader were vital for internal initiation. Functionally, exposure to potassium chloride or intracellular acidification and addition of polyinosinic:polycytidylic acid as mimics of neural activity and double stranded RNA, respectively, differentially affected FMR1 IRES activity. Conclusion Our results indicate that multiple stimuli influence IRES-dependent translation of the FMR1 mRNA and suggest a functional role for the CGG nucleotide repeats.
Viral Genome-Linked Protein (VPg Is Essential for Translation Initiation of Rabbit Hemorrhagic Disease Virus (RHDV.

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Jie Zhu

Full Text Available Rabbit hemorrhagic disease virus (RHDV, the causative agent of rabbit hemorrhagic disease, is an important member of the caliciviridae family. Currently, no suitable tissue culture system is available for proliferating RHDV, limiting the study of the pathogenesis of RHDV. In addition, the mechanisms underlying RHDV translation and replication are largely unknown compared with other caliciviridae viruses. The RHDV replicon recently constructed in our laboratory provides an appropriate model to study the pathogenesis of RHDV without in vitro RHDV propagation and culture. Using this RHDV replicon, we demonstrated that the viral genome-linked protein (VPg is essential for RHDV translation in RK-13 cells for the first time. In addition, we showed that VPg interacts with eukaryotic initiation factor 4E (eIF4E in vivo and in vitro and that eIF4E silencing inhibits RHDV translation, suggesting the interaction between VPg and eIF4E is involved in RHDV translation. Our results support the hypothesis that VPg serves as a novel cap substitute during the initiation of RHDV translation.
IRES-dependent translational control during virus-induced endoplasmic reticulum stress and apoptosis

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Paul eHanson

2012-03-01

Full Text Available Many virus infections and stresses can induce endoplasmic reticulum (ER stress response, a host self defense mechanism against viral invasion and stress. During this event, viral and cellular gene expression is actively regulated and often encounters a switching of the translation initiation from cap-dependent to IRES (internal ribosome entry sites-dependent. This switching is largely dependent on the mRNA structure of the 5’untranslated region (5’UTR and on the particular stress stimuli. Picornviruses and some other viruses contain an IRES within their 5’UTR of viral genome and employ an IRES-driven mechanism for translation initiation. Recently, a growing number of cellular genes involved in growth control, cell cycle progression and apoptosis were also found to contain one or more IRES within their long highly structured 5’UTRs. These genes initiate translation usually by a cap-dependent mechanism under normal physiological conditions; however, in certain environments, such as infection, starvation and heat shock they shift translation initiation to an IRES-dependent modality. Although the molecular mechanism is not entirely understood, a number of studies have revealed that several cellular biochemical processes are responsible for the switching of translation initiation to IRES-dependent. These include the cleavage of translation initiation factors by viral and/or host proteases, phosphorylation (inactivation of host factors for translation initiation, over-production of homologous proteins of cap-binding protein eIF4E, suppression of cap-binding protein eIF4E expression by specific microRNA, activation of enzymes for mRNA decapping, as well as others. Here, we summarize the recent advances in our understanding of the molecular mechanisms for the switching of translation initiation, particularly for the proteins involved in cell survival and apoptosis in the ER stress pathways during viral infections.
Modifying the 5'-Cap for Click Reactions of Eukaryotic mRNA and To Tune Translation Efficiency in Living Cells.

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Holstein, Josephin M; Anhäuser, Lea; Rentmeister, Andrea

2016-08-26

The 5'-cap is a hallmark of eukaryotic mRNAs and plays fundamental roles in RNA metabolism, ranging from quality control to export and translation. Modifying the 5'-cap may thus enable modulation of the underlying processes and investigation or tuning of several biological functions. A straightforward approach is presented for the efficient production of a range of N7-modified caps based on the highly promiscuous methyltransferase Ecm1. We show that these, as well as N(2) -modified 5'-caps, can be used to tune translation of the respective mRNAs both in vitro and in cells. Appropriate modifications allow subsequent bioorthogonal chemistry, as demonstrated by intracellular live-cell labeling of a target mRNA. The efficient and versatile N7 manipulation of the mRNA cap makes mRNAs amenable to both modulation of their biological function and intracellular labeling, and represents a valuable addition to the chemical biology toolbox. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Dengue virus-induced regulation of the host cell translational machinery

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C.S.A. Villas-Bôas

2009-11-01

Full Text Available Dengue virus (DV-induced changes in the host cell protein synthesis machinery are not well understood. We investigated the transcriptional changes related to initiation of protein synthesis. The human hepatoma cell line, HepG2, was infected with DV serotype 2 for 1 h at a multiplicity of infection of one. RNA was extracted after 6, 24 and 48 h. Microarray results showed that 36.5% of the translation factors related to initiation of protein synthesis had significant differential expression (Z-score ≥ ±2.0. Confirmation was obtained by quantitative real-time reverse transcription-PCR. Of the genes involved in the activation of mRNA for cap-dependent translation (eIF4 factors, eIF4A, eIF4G1 and eIF4B were up-regulated while the negative regulator of translation eIF4E-BP3 was down-regulated. This activation was transient since at 24 h post-infection levels were not significantly different from control cells. However, at 48 h post-infection, eIF4A, eIF4E, eIF4G1, eIF4G3, eIF4B, and eIF4E-BP3 were down-regulated, suggesting that cap-dependent translation could be inhibited during the progression of infection. To test this hypothesis, phosphorylation of p70S6K and 4E-BP1, which induce cap-dependent protein synthesis, was assayed. Both proteins remained phosphorylated when assayed at 6 h after infection, while infection induced dephosphorylation of p70S6K and 4E-BP1 at 24 and 48 h of infection, respectively. Taken together, these results provide biological evidence suggesting that in HepG2 cells DV sustains activation of the cap-dependent machinery at early stages of infection, but progression of infection switches protein synthesis to a cap-independent process.
Translation initiation complex eIF4F is a therapeutic target for dual mTOR kinase inhibitors in non-Hodgkin lymphoma

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Stenson, Mary J.; Maurer, Matthew J.; Wellik, Linda E.; Link, Brian; Hege, Kristen; Dogan, Ahmet; Sotomayor, Eduardo; Witzig, Thomas; Gupta, Mamta

2015-01-01

Deregulated mRNA translation has been implicated in disease development and in part is controlled by a eukaryotic initiation complex eIF4F (composed of eIF4E, eIF4G and eIF4A). We demonstrate here that the cap bound fraction from lymphoma cells was enriched with eIF4G and eIF4E indicating that lymphoma cells exist in an activated translational state. Moreover, 77% (110/142) of diffuse large B cell lymphoma tumors expressed eIF4E and this was associated with an inferior event free survival. Over-expression of wild-type eIF4E (eIF4EWT) but not cap-mutant eIF4E (eIF4Ecap mutant) increased the activation of the eIF4F complex. Treatment with the active-site dual mTOR inhibitor CC214-1 reduced the level of the eIF4F complex by decreasing the cap bound fraction of eIF4G and increasing the levels of 4E-BP1. CC214-1 inhibited both the cap dependent and global protein translation. CC214-1 inhibited c-Myc, and cyclin D3 translation by decreasing polysomal fractions from lymphoma cells. Inhibition of eIF4E with shRNA further decreased the CC214-1 induced inhibition of the eIF4F complex, c-Myc, cyclin D3 translation, and colony formation. These studies demonstrate that the eIF4F complex is deregulated in aggressive lymphoma and that dual mTOR therapy has therapeutic potential in these patients. PMID:25839159
Pioneer round of translation occurs during serum starvation

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Oh, Nara; Kim, Kyoung Mi; Cho, Hana; Choe, Junho; Kim, Yoon Ki

2007-01-01

The pioneer round of translation plays a role in translation initiation of newly spliced and exon junction complex (EJC)-bound mRNAs. Nuclear cap-binding protein complex CBP80/20 binds to those mRNAs at the 5'-end, recruiting translation initiation complex. As a consequence of the pioneer round of translation, the bound EJCs are dissociated from mRNAs and CBP80/20 is replaced by the cytoplasmic cap-binding protein eIF4E. Steady-state translation directed by eIF4E allows for an immediate and rapid response to changes in physiological conditions. Here, we show that nonsense-mediated mRNA decay (NMD), which restricts only to the pioneer round of translation but not to steady-state translation, efficiently occurs even during serum starvation, in which steady-state translation is drastically abolished. Accordingly, CBP80 remains in the nucleus and processing bodies are unaffected in their abundance and number in serum-starved conditions. These results suggest that mRNAs enter the pioneer round of translation during serum starvation and are targeted for NMD if they contain premature termination codons
Secretory Vesicle Priming by CAPS Is Independent of Its SNARE-Binding MUN Domain

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Cuc Quynh Nguyen Truong

2014-11-01

Full Text Available Priming of secretory vesicles is a prerequisite for their Ca2+-dependent fusion with the plasma membrane. The key vesicle priming proteins, Munc13s and CAPSs, are thought to mediate vesicle priming by regulating the conformation of the t-SNARE syntaxin, thereby facilitating SNARE complex assembly. Munc13s execute their priming function through their MUN domain. Given that the MUN domain of Ca2+-dependent activator protein for secretion (CAPS also binds syntaxin, it was assumed that CAPSs prime vesicles through the same mechanism as Munc13s. We studied naturally occurring splice variants of CAPS2 in CAPS1/CAPS2-deficient cells and found that CAPS2 primes vesicles independently of its MUN domain. Instead, the pleckstrin homology domain of CAPS2 seemingly is essential for its priming function. Our findings indicate a priming mode for secretory vesicles. This process apparently requires membrane phospholipids, does not involve the binding or direct conformational regulation of syntaxin by MUN domains of CAPSs, and is therefore not redundant with Munc13 action.
Interaction in vitro between the proteinase of Tomato ringspot virus (genus Nepovirus) and the eukaryotic translation initiation factor iso4E from Arabidopsis thaliana.

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Léonard, Simon; Chisholm, Joan; Laliberté, Jean-François; Sanfaçon, Hélène

2002-08-01

Eukaryotic initiation factor eIF(iso)4E binds to the cap structure of mRNAs leading to assembly of the translation complex. This factor also interacts with the potyvirus VPg and this interaction has been correlated with virus infectivity. In this study, we show an interaction between eIF(iso)4E and the proteinase (Pro) of a nepovirus (Tomato ringspot virus; ToRSV) in vitro. The ToRSV VPg did not interact with eIF(iso)4E although its presence on the VPg-Pro precursor increased the binding affinity of Pro for the initiation factor. A major determinant of the interaction was mapped to the first 93 residues of Pro. Formation of the complex was inhibited by addition of m(7)GTP (a cap analogue), suggesting that Pro-containing molecules compete with cellular mRNAs for eIF(iso)4E binding. The possible implications of this interaction for translation and/or replication of the virus genome are discussed.
Deregulation of cap-dependent mRNA translation increases tumour radiosensitivity through reduction of the hypoxic fraction

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Rouschop, Kasper M.A.; Dubois, Ludwig; Schaaf, Marco B.E.; Beucken, Twan van den; Lieuwes, Natasja; Keulers, Tom G.H.; Savelkouls, Kim G.M.; Bussink, Johan; Kogel, Albert J. van der; Koritzinsky, Marianne; Wouters, Bradly G.

2011-01-01

Background and purpose: Tumour hypoxia is an important limiting factor in the successful treatment of cancer. Adaptation to hypoxia includes inhibition of mTOR, causing scavenging of eukaryotic initiation factor 4E (eIF4E), the rate-limiting factor for cap-dependent translation. The aim of this study was to determine the effect of preventing mTOR-dependent translation inhibition on hypoxic cell survival and tumour sensitivity towards irradiation. Material and methods: The effect of eIF4E-overexpression on cell proliferation, hypoxia-tolerance, and radiation sensitivity was assessed using isogenic, inducible U373 and HCT116 cells. Results: We found that eIF4E-overexpression significantly enhanced proliferation of cells under normal conditions, but not during hypoxia, caused by increased cell death during hypoxia. Furthermore, eIF4E-overexpression stimulated overall rates of tumour growth, but resulted in selective loss of hypoxic cells in established tumours and increased levels of necrosis. This markedly increased overall tumour sensitivity to irradiation. Conclusions: Our results demonstrate that hypoxia induced inhibition of translational control through regulation of eIF4E is an important mediator of hypoxia tolerance and radioresistance of tumours. These data also demonstrate that deregulation of metabolic pathways such as mTOR can influence the proliferation and survival of tumour cells experiencing metabolic stress in opposite ways of nutrient replete cells.
Ectopic expression of eIF4E-transporter triggers the movement of eIF4E into P-bodies, inhibiting steady-state translation but not the pioneer round of translation

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Lee, Hyung Chul; Cho, Hana; Kim, Yoon Ki

2008-01-01

Nonsense-mediated mRNA decay (NMD) is the best-characterized mRNA surveillance mechanism; this process removes faulty mRNAs harboring premature termination codons (PTCs). NMD targets newly synthesized mRNAs bound by nuclear cap-binding proteins 80/20 (CBP80/20) and exon junction complex (EJC), the former of which is thought to recruit the ribosome to initiate the pioneer round of translation. After completion of the pioneer round of translation, CBP80/20 is replaced by the cytoplasmic cap-binding protein eIF4E, which mediates steady-state translation in the cytoplasm. Here, we show that overexpression of eIF4E-T preferentially inhibits cap-dependent steady-state translation, but not the pioneer round of translation. We also demonstrate that overexpression of eIF4E-T or Dcp1a triggers the movement of eIF4E into the processing bodies. These results suggest that the pioneer round of translation differs from steady-state translation in terms of ribosome recruitment
Cap-dependent translational control of oncolytic measles virus infection in malignant mesothelioma.

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Jacobson, Blake A; Sadiq, Ahad A; Tang, Shaogeng; Jay-Dixon, Joe; Patel, Manish R; Drees, Jeremy; Sorenson, Brent S; Russell, Stephen J; Kratzke, Robert A

2017-09-08

Malignant mesothelioma has a poor prognosis for which there remains an urgent need for successful treatment approaches. Infection with the Edmonston vaccine strain (MV-Edm) derivative of measles virus results in lysis of cancer cells and has been tested in clinical trials for numerous tumor types including mesothelioma. Many factors play a role in MV-Edm tumor cell selectivity and cytopathic activity while also sparing non-cancerous cells. The MV-Edm receptor CD46 (cluster of differentiation 46) was demonstrated to be significantly higher in mesothelioma cells than in control cells. In contrast, mesothelioma cells are not reliant upon the alternative MV-Edm receptor nectin-4 for entry. MV-Edm treatment of mesothelioma reduced cell viability and also invoked apoptotic cell death. Forced expression of eIF4E or translation stimulation following IGF-I (insulin-like growth factor 1) exposure strengthened the potency of measles virus oncolytic activity. It was also shown that repression of cap-dependent translation by treatment with agents [4EASO, 4EGI-1] that suppress host cell translation or by forcing cells to produce an activated repressor protein diminishes the strength of oncolytic viral efficacy.

Crimean-Congo Hemorrhagic Fever Virus Nucleocapsid Protein Augments mRNA Translation.

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Jeeva, Subbiah; Cheng, Erdong; Ganaie, Safder S; Mir, Mohammad A

2017-08-01

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne Nairovirus of the Bunyaviridae family, causing severe illness with high mortality rates in humans. Here, we demonstrate that CCHFV nucleocapsid protein (CCHFV-NP) augments mRNA translation. CCHFV-NP binds to the viral mRNA 5' untranslated region (UTR) with high affinity. It facilitates the translation of reporter mRNA both in vivo and in vitro with the assistance of the viral mRNA 5' UTR. CCHFV-NP equally favors the translation of both capped and uncapped mRNAs, demonstrating the independence of this translation strategy on the 5' cap. Unlike the canonical host translation machinery, inhibition of eIF4F complex, an amalgam of three initiation factors, eIF4A, eIF4G, and eIF4E, by the chemical inhibitor 4E1RCat did not impact the CCHFV-NP-mediated translation mechanism. However, the proteolytic degradation of eIF4G alone by the human rhinovirus 2A protease abrogated this translation strategy. Our results demonstrate that eIF4F complex formation is not required but eIF4G plays a critical role in this translation mechanism. Our results suggest that CCHFV has adopted a unique translation mechanism to facilitate the translation of viral mRNAs in the host cell cytoplasm where cellular transcripts are competing for the same translation apparatus. IMPORTANCE Crimean-Congo hemorrhagic fever, a highly contagious viral disease endemic to more than 30 countries, has limited treatment options. Our results demonstrate that NP favors the translation of a reporter mRNA harboring the viral mRNA 5' UTR. It is highly likely that CCHFV uses an NP-mediated translation strategy for the rapid synthesis of viral proteins during the course of infection. Shutdown of this translation mechanism might selectively impact viral protein synthesis, suggesting that an NP-mediated translation strategy is a target for therapeutic intervention against this viral disease. Copyright © 2017 American Society for Microbiology.
Silibinin inhibits translation initiation: implications for anticancer therapy.

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Lin, Chen-Ju; Sukarieh, Rami; Pelletier, Jerry

2009-06-01

Silibinin is a nontoxic flavonoid reported to have anticancer properties. In this study, we show that silibinin exhibits antiproliferative activity on MCF-7 breast cancer cells. Exposure to silibinin leads to a concentration-dependent decrease in global protein synthesis associated with reduced levels of eukaryotic initiation factor 4F complex. Moreover, polysome profile analysis of silibinin-treated cells shows a decrease in polysome content and translation of cyclin D1 mRNA. Silibinin exerts its effects on translation initiation by inhibiting the mammalian target of rapamycin signaling pathway by acting upstream of TSC2. Our results show that silibinin blocks mammalian target of rapamycin signaling with a concomitant reduction in translation initiation, thus providing a possible molecular mechanism of how silibinin can inhibit growth of transformed cells.
Translation initiation factor AteIF(iso4E is involved in selective mRNA translation in Arabidopsis thaliana seedlings.

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Ana Valeria Martínez-Silva

Full Text Available One of the most regulated steps of translation initiation is the recruitment of mRNA by the translation machinery. In eukaryotes, this step is mediated by the 5'end cap-binding factor eIF4E bound to the bridge protein eIF4G and forming the eIF4F complex. In plants, different isoforms of eIF4E and eIF4G form the antigenically distinct eIF4F and eIF(iso4F complexes proposed to mediate selective translation. Using a microarray analysis of polyribosome- and non-polyribosome-purified mRNAs from 15 day-old Arabidopsis thaliana wild type [WT] and eIF(iso4E knockout mutant [(iso4E-1] seedlings we found 79 transcripts shifted from polyribosomes toward non-polyribosomes, and 47 mRNAs with the opposite behavior in the knockout mutant. The translationally decreased mRNAs were overrepresented in root-preferentially expressed genes and proteins from the endomembrane system, including several transporters such as the phosphate transporter PHOSPHATE1 (PHO1, Sucrose transporter 3 (SUC3, ABC transporter-like with ATPase activity (MRP11 and five electron transporters, as well as signal transduction-, protein modification- and transcription-related proteins. Under normal growth conditions, eIF(iso4E expression under the constitutive promoter 35 S enhanced the polyribosomal recruitment of PHO1 supporting its translational preference for eIF(iso4E. Furthermore, under phosphate deficiency, the PHO1 protein increased in the eIF(iso4E overexpressing plants and decreased in the knockout mutant as compared to wild type. In addition, the knockout mutant had larger root, whereas the 35 S directed expression of eIF(iso4E caused shorter root under normal growth conditions, but not under phosphate deficiency. These results indicate that selective translation mediated by eIF(iso4E is relevant for Arabidopsis root development under normal growth conditions.
Internal ribosomal entry site-mediated translation is important for rhythmic PERIOD1 expression.

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Kyung-Ha Lee

Full Text Available The mouse PERIOD1 (mPER1 plays an important role in the maintenance of circadian rhythm. Translation of mPer1 is directed by both a cap-dependent process and cap-independent translation mediated by an internal ribosomal entry site (IRES in the 5' untranslated region (UTR. Here, we compared mPer1 IRES activity with other cellular IRESs. We also found critical region in mPer1 5'UTR for heterogeneous nuclear ribonucleoprotein Q (HNRNPQ binding. Deletion of HNRNPQ binding region markedly decreased IRES activity and disrupted rhythmicity. A mathematical model also suggests that rhythmic IRES-dependent translation is a key process in mPER1 oscillation. The IRES-mediated translation of mPer1 will help define the post-transcriptional regulation of the core clock genes.
Predicting Translation Initiation Rates for Designing Synthetic Biology

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Reeve, Benjamin; Hargest, Thomas; Gilbert, Charlie; Ellis, Tom

2014-01-01

In synthetic biology, precise control over protein expression is required in order to construct functional biological systems. A core principle of the synthetic biology approach is a model-guided design and based on the biological understanding of the process, models of prokaryotic protein production have been described. Translation initiation rate is a rate-limiting step in protein production from mRNA and is dependent on the sequence of the 5′-untranslated region and the start of the coding sequence. Translation rate calculators are programs that estimate protein translation rates based on the sequence of these regions of an mRNA, and as protein expression is proportional to the rate of translation initiation, such calculators have been shown to give good approximations of protein expression levels. In this review, three currently available translation rate calculators developed for synthetic biology are considered, with limitations and possible future progress discussed.
Translation of a nonpolyadenylated viral RNA is enhanced by binding of viral coat protein or polyadenylation of the RNA.

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Neeleman, L; Olsthoorn, R C; Linthorst, H J; Bol, J F

2001-12-04

On entering a host cell, positive-strand RNA virus genomes have to serve as messenger for the translation of viral proteins. Efficient translation of cellular messengers requires interactions between initiation factors bound to the 5'-cap structure and the poly(A) binding protein bound to the 3'-poly(A) tail. Initiation of infection with the tripartite RNA genomes of alfalfa mosaic virus (AMV) and viruses from the genus Ilarvirus requires binding of a few molecules of coat protein (CP) to the 3' end of the nonpolyadenylated viral RNAs. Moreover, infection with the genomic RNAs can be initiated by addition of the subgenomic messenger for CP, RNA 4. We report here that extension of the AMV RNAs with a poly(A) tail of 40 to 80 A-residues permitted initiation of infection independently of CP or RNA 4 in the inoculum. Specifically, polyadenylation of RNA 1 relieved an apparent bottleneck in the translation of the viral RNAs. Translation of RNA 4 in plant protoplasts was autocatalytically stimulated by its encoded CP. Mutations that interfered with CP binding to the 3' end of viral RNAs reduced translation of RNA 4 to undetectable levels. Possibly, CP of AMV and ilarviruses stimulates translation of viral RNAs by acting as a functional analogue of poly(A) binding protein or other cellular proteins.
Influence of Translation Initiation on Organellar Protein Targeting in Arabidopsis

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Sally A. Mackenzie

2011-04-18

A primary focus of the Mackenzie laboratory is the elucidation of processes and machinery for mitochondrial genome maintenance and transmission in higher plants. We have found that numerous organellar DNA maintenance components in plants appear to be dual targeted to mitochondria and plastids. Of particular interest was the observation that some twin (tandemly arrayed) dual targeting presequences appeared to utilize non-AUG alternative translation initiation, allowing for multiple translation starts at a single gene. Two aspects of this phenomenon were of particular interest: (1) Alternative translation initiation might provide a mechanism to regulate protein targeting temporally and spatially, a possibility that had not been demonstrated previously, and (2) alternative translation initiation might occur in genes involved in nuclear-controlled mitochondrial genome recombination, thought to be exclusively mitochondrial in their function. During the course of this research, we pursued three aims, with an emphasis on two specific genes of interest: POLgamma2, an organellar DNA polymerase, and MSH1, a MutS homolog thought to participate in mitochondrial, but not plastid, genome recombination surveillance. Our aims were to (1) Identify additional genes within Arabidopsis and other genomes that employ non-AUG alternative translation initiation, (2) Locate sequences upstream to the annotated AUG that confer alternative non-AUG translation initiation activity, and (3) Identify cis and trans factors that influence start site selection in genes with non-AUG starts. Toward these ends, we have shown that non-AUG initiation occurs in a number of genes, likely influencing targeting behavior of the protein. We have also shown that start site selection is strongly influenced by Kozak consensus sequence environment, indicating that alternative translation initiation in plants occurs by relaxation of ribosome scanning.
Regulation of translation during cancer progression

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Petz, M.

2012-01-01

Laminin B1 (LamB1) is a main component of the extracellular matrix and is involved in the regulation of tumor cell migration and invasion of during carcinogenesis. Metastasis of carcinoma cells is crucially linked to the process of epithelial to mesenchymal transition (EMT), which allows tumor cells to acquire a more motile phenotype and to dissociate from the epithelial cell cluster of the tumor. Expression profiling of polysome-associated mRNA revealed LamB1 to be translationally upregulated upon EMT of malignant hepatocytes. The enhanced translation of LamB1 in metastatic hepatocytes proved to be regulated by an internal ribosome entry site (IRES) located within the 5’-untranslated region (UTR) of the LamB1 transcript. IRES activity was detected by employing two independent reporter systems and verified by stringent assays for the presence of cryptic promoter or splice sites. The minimal cis-acting IRES sequence of 293 nucleotides that is required for cap-independent translation was localized directly upstream of the start codon. Notably, the IRES trans-acting factor (ITAF) La was identified by RNA affinity purification as regulatory factor that interacts with LamB1 5’-UTR. This interaction was verified by RNA-immunoprecipitation in vivo, which revealed enhanced binding of La to the minimal IRES motif of LamB1 after EMT. Consistently, cytoplasmic levels of La were elevated in EMT-transformed cells and correlated with increased LamB1 protein expression. Furthermore, IRES-driven translation of LamB1 was elevated in the presence of La in vitro. Importantly, the EMT-induced cytoplasmic translocation of La was found to be triggered by platelet derived growth factor (PDGF) that is downstream of transforming growth factor (TGF)-β signaling. Together, these data demonstrate that La interacts with the LamB1 IRES in the cytoplasm, resulting in enhanced cap-independent translation of LamB1 in malignant hepatocytes that have undergone EMT. (author) [de
Untranslated regions of diverse plant viral RNAs vary greatly in translation enhancement efficiency

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Fan Qiuling

2012-05-01

Full Text Available Abstract Background Whole plants or plant cell cultures can serve as low cost bioreactors to produce massive amounts of a specific protein for pharmacological or industrial use. To maximize protein expression, translation of mRNA must be optimized. Many plant viral RNAs harbor extremely efficient translation enhancers. However, few of these different translation elements have been compared side-by-side. Thus, it is unclear which are the most efficient translation enhancers. Here, we compare the effects of untranslated regions (UTRs containing translation elements from six plant viruses on translation in wheat germ extract and in monocotyledenous and dicotyledenous plant cells. Results The highest expressing uncapped mRNAs contained viral UTRs harboring Barley yellow dwarf virus (BYDV-like cap-independent translation elements (BTEs. The BYDV BTE conferred the most efficient translation of a luciferase reporter in wheat germ extract and oat protoplasts, while uncapped mRNA containing the BTE from Tobacco necrosis virus-D translated most efficiently in tobacco cells. Capped mRNA containing the Tobacco mosaic virus omega sequence was the most efficient mRNA in tobacco cells. UTRs from Satellite tobacco necrosis virus, Tomato bushy stunt virus, and Crucifer-infecting tobamovirus (crTMV did not stimulate translation efficiently. mRNA with the crTMV 5′ UTR was unstable in tobacco protoplasts. Conclusions BTEs confer the highest levels of translation of uncapped mRNAs in vitro and in vivo, while the capped omega sequence is most efficient in tobacco cells. These results provide a basis for understanding mechanisms of translation enhancement, and for maximizing protein synthesis in cell-free systems, transgenic plants, or in viral expression vectors.
Translational control of human acetyl-CoA carboxylase 1 mRNA is mediated by an internal ribosome entry site in response to ER stress, serum deprivation or hypoxia mimetic CoCl2.

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Damiano, Fabrizio; Testini, Mariangela; Tocci, Romina; Gnoni, Gabriele V; Siculella, Luisa

2018-04-01

Acetyl-CoA carboxylase 1 (ACC1) is a cytosolic enzyme catalyzing the rate limiting step in de novo fatty acid biosynthesis. There is mounting evidence showing that ACC1 is susceptible to dysregulation and that it is over-expressed in liver diseases associated with lipid accumulation and in several cancers. In the present study, ACC1 regulation at the translational level is reported. Using several experimental approaches, the presence of an internal ribosome entry site (IRES) has been established in the 5' untranslated region (5' UTR) of the ACC1 mRNA. Transfection experiments with the ACC1 5' UTR inserted in a dicistronic reporter vector show a remarkable increase in the downstream cistron translation, through a cap-independent mechanism. The endoplasmic reticulum (ER) stress condition and the related unfolded protein response (UPR), triggered by treatment with thapsigargin and tunicamycin, cause an increase of the cap-independent translation of ACC1 mRNA in HepG2 cells, despite the overall reduction in global protein synthesis. Other stress conditions, such as serum starvation and incubation with hypoxia mimetic agent CoCl 2 , up-regulate ACC1 expression in HepG2 cells at the translational level. Overall, these findings indicate that the presence of an IRES in the ACC1 5' UTR allows ACC1 mRNA translation in conditions that are inhibitory to cap-dependent translation. A potential involvement of the cap-independent translation of ACC1 in several pathologies, such as obesity and cancer, has been discussed. Copyright © 2018 Elsevier B.V. All rights reserved.
Sapovirus translation requires an interaction between VPg and the cap binding protein eIF4E.

Science.gov (United States)

Hosmillo, Myra; Chaudhry, Yasmin; Kim, Deok-Song; Goodfellow, Ian; Cho, Kyoung-Oh

2014-11-01

Sapoviruses of the Caliciviridae family of small RNA viruses are emerging pathogens that cause gastroenteritis in humans and animals. Molecular studies on human sapovirus have been hampered due to the lack of a cell culture system. In contrast, porcine sapovirus (PSaV) can be grown in cell culture, making it a suitable model for understanding the infectious cycle of sapoviruses and the related enteric caliciviruses. Caliciviruses are known to use a novel mechanism of protein synthesis that relies on the interaction of cellular translation initiation factors with the virus genome-encoded viral protein genome (VPg) protein, which is covalently linked to the 5' end of the viral genome. Using PSaV as a representative member of the Sapovirus genus, we characterized the role of the viral VPg protein in sapovirus translation. As observed for other caliciviruses, the PSaV genome was found to be covalently linked to VPg, and this linkage was required for the translation and the infectivity of viral RNA. The PSaV VPg protein was associated with the 4F subunit of the eukaryotic translation initiation factor (eIF4F) complex in infected cells and bound directly to the eIF4E protein. As has been previously demonstrated for feline calicivirus, a member of the Vesivirus genus, PSaV translation required eIF4E and the interaction between eIF4E and eIF4G. Overall, our study provides new insights into the novel mechanism of sapovirus translation, suggesting that sapovirus VPg can hijack the cellular translation initiation mechanism by recruiting the eIF4F complex through a direct eIF4E interaction. Sapoviruses, which are members of the Caliciviridae family, are one of the causative agents of viral gastroenteritis in humans. However, human sapovirus remains noncultivable in cell culture, hampering the ability to characterize the virus infectious cycle. Here, we show that the VPg protein from porcine sapovirus, the only cultivatable sapovirus, is essential for viral translation and
Protein phosphatase PPM1G regulates protein translation and cell growth by dephosphorylating 4E binding protein 1 (4E-BP1).

Science.gov (United States)

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

2013-08-09

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

Science.gov (United States)

May, Jared; Johnson, Philip; Saleem, Huma; Simon, Anne E

2017-04-15

To maximize the coding potential of viral genomes, internal ribosome entry sites (IRES) can be used to bypass the traditional requirement of a 5' cap and some/all of the associated translation initiation factors. Although viral IRES typically contain higher-order RNA structure, an unstructured sequence of about 84 nucleotides (nt) immediately upstream of the Turnip crinkle virus (TCV) coat protein (CP) open reading frame (ORF) has been found to promote internal expression of the CP from the genomic RNA (gRNA) both in vitro and in vivo An absence of extensive RNA structure was predicted using RNA folding algorithms and confirmed by selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) RNA structure probing. Analysis of the IRES region in vitro by use of both the TCV gRNA and reporter constructs did not reveal any sequence-specific elements but rather suggested that an overall lack of structure was an important feature for IRES activity. The CP IRES is A-rich, independent of orientation, and strongly conserved among viruses in the same genus. The IRES was dependent on eIF4G, but not eIF4E, for activity. Low levels of CP accumulated in vivo in the absence of detectable TCV subgenomic RNAs, strongly suggesting that the IRES was active in the gRNA in vivo Since the TCV CP also serves as the viral silencing suppressor, early translation of the CP from the viral gRNA is likely important for countering host defenses. Cellular mRNA IRES also lack extensive RNA structures or sequence conservation, suggesting that this viral IRES and cellular IRES may have similar strategies for internal translation initiation. IMPORTANCE Cap-independent translation is a common strategy among positive-sense, single-stranded RNA viruses for bypassing the host cell requirement of a 5' cap structure. Viral IRES, in general, contain extensive secondary structure that is critical for activity. In contrast, we demonstrate that a region of viral RNA devoid of extensive secondary
Regulation of mRNA Translation Is a Novel Mechanism for Phthalate Toxicity.

Directory of Open Access Journals (Sweden)

Jun Ling

Full Text Available Phthalates are a group of plasticizers that are widely used in many consumer products and medical devices, thus generating a huge burden to human health. Phthalates have been known to cause a number of developmental and reproductive disorders functioning as endocrine modulators. They are also involved in carcinogenesis with mechanisms less understood. To further understand the molecular mechanisms of phthalate toxicity, in this study we reported a new effect of phthalates on mRNA translation/protein synthesis, a key regulatory step of gene expression. Butyl benzyl phthalate (BBP was found to directly inhibit mRNA translation in vitro but showed a complicated pattern of affecting mRNA translation in cells. In human kidney embryonic cell (HEK-293T, BBP increased cap-dependent mRNA translation at lower concentrations but showed inhibitory effect at higher concentrations. Cap-independent translation was not affected. On the other hand, mono (2-ethylhexyl phthalate (MEHP as a major metabolite of another important phthalate di (2-ethylhexyl phthalate (DEHP inhibited both can-dependent and -independent mRNA translation in vivo. In contrast, BBP and MEHP exhibited an overall promoting effect on mRNA translation in cancer cells. Mechanistic studies identified that the level and phosphorylation of eIF4E-BP (eIF4E binding protein and the amount of eIF4GI in eIF4F complex were altered in accordance with the effect of BBP on translation. BBP was also identified to directly bind to eIF4E, providing a further mechanism underlying the regulation of mRNA by phthalate. At the cellular level BBP inhibited normal cell growth but slightly promoted cancer cells (HT29 growth. Overall, this study provides the first evidence that phthalates can directly regulate mRNA translation as a novel mechanism to mediate their biological toxicities.
Engineering bacterial translation initiation - Do we have all the tools we need?

Science.gov (United States)

Vigar, Justin R J; Wieden, Hans-Joachim

2017-11-01

Reliable tools that allow precise and predictable control over gene expression are critical for the success of nearly all bioengineering applications. Translation initiation is the most regulated phase during protein biosynthesis, and is therefore a promising target for exerting control over gene expression. At the translational level, the copy number of a protein can be fine-tuned by altering the interaction between the translation initiation region of an mRNA and the ribosome. These interactions can be controlled by modulating the mRNA structure using numerous approaches, including small molecule ligands, RNAs, or RNA-binding proteins. A variety of naturally occurring regulatory elements have been repurposed, facilitating advances in synthetic gene regulation strategies. The pursuit of a comprehensive understanding of mechanisms governing translation initiation provides the framework for future engineering efforts. Here we outline state-of-the-art strategies used to predictably control translation initiation in bacteria. We also discuss current limitations in the field and future goals. Due to its function as the rate-determining step, initiation is the ideal point to exert effective translation regulation. Several engineering tools are currently available to rationally design the initiation characteristics of synthetic mRNAs. However, improvements are required to increase the predictability, effectiveness, and portability of these tools. Predictable and reliable control over translation initiation will allow greater predictability when designing, constructing, and testing genetic circuits. The ability to build more complex circuits predictably will advance synthetic biology and contribute to our fundamental understanding of the underlying principles of these processes. "This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2017 Elsevier
The role of mRNA translation in the adaptation to hypoxia

International Nuclear Information System (INIS)

Koritzinsky, M.; Wouters, B.G.; Koumenis, C.

2003-01-01

Hypoxia commonly occurs in human tumours and is associated with a poor prognosis. We and others have shown that global mRNA translation is rapidly inhibited during hypoxia. However, some mRNAs, such as those coding for HIF-1 α and VEGF, remain efficiently translated. We therefore hypothesize that the inhibition of mRNA translation serves to promote hypoxia tolerance in two ways: i) through conservation of energy and ii) through differential gene expression involved in hypoxia adaptation. We are investigating the mechanisms responsible for the down regulation of protein synthesis during hypoxia, and how specific mRNAs maintain their ability to be translated under such conditions. Our goal is to understand the significance of these regulatory mechanisms for hypoxia tolerance in vitro and tumor growth in vivo. We have previously shown that one mechanism responsible for inhibiting protein synthesis during hypoxia is the activation of PERK, which inhibits the essential translation factor eIF2 α . Here we show that PERK-/- MEFs are not able to inhibit protein synthesis efficiently during hypoxia and are significantly less tolerant to hypoxia than wt cells. We also show that other mechanisms are important for sustained low protein synthesis during chronic hypoxia. We demonstrate that the eIF4F complex is disrupted during prolonged hypoxia, and that this is mediated by 4E-BP1 and 4E-T. eIF4F is essential for translation which is dependent upon the 5'mRNA cap-structure. These studies therefore indicate a switch from the inhibition of all translation through eIF2 α during acute hypoxia, to the inhibition of only cap-dependent translation during chronic hypoxia. This model predicts the differential induction of genes that can be translated cap-independently during chronic hypoxia, which is consistent with the observed differential translation of HIF-1 α and VEGF. The functional significance of the disruption of the eIF4F complex during hypoxia is currently being addressed
Initiation of translation in bacteria by a structured eukaryotic IRES RNA.

Science.gov (United States)

Colussi, Timothy M; Costantino, David A; Zhu, Jianyu; Donohue, John Paul; Korostelev, Andrei A; Jaafar, Zane A; Plank, Terra-Dawn M; Noller, Harry F; Kieft, Jeffrey S

2015-03-05

The central dogma of gene expression (DNA to RNA to protein) is universal, but in different domains of life there are fundamental mechanistic differences within this pathway. For example, the canonical molecular signals used to initiate protein synthesis in bacteria and eukaryotes are mutually exclusive. However, the core structures and conformational dynamics of ribosomes that are responsible for the translation steps that take place after initiation are ancient and conserved across the domains of life. We wanted to explore whether an undiscovered RNA-based signal might be able to use these conserved features, bypassing mechanisms specific to each domain of life, and initiate protein synthesis in both bacteria and eukaryotes. Although structured internal ribosome entry site (IRES) RNAs can manipulate ribosomes to initiate translation in eukaryotic cells, an analogous RNA structure-based mechanism has not been observed in bacteria. Here we report our discovery that a eukaryotic viral IRES can initiate translation in live bacteria. We solved the crystal structure of this IRES bound to a bacterial ribosome to 3.8 Å resolution, revealing that despite differences between bacterial and eukaryotic ribosomes this IRES binds directly to both and occupies the space normally used by transfer RNAs. Initiation in both bacteria and eukaryotes depends on the structure of the IRES RNA, but in bacteria this RNA uses a different mechanism that includes a form of ribosome repositioning after initial recruitment. This IRES RNA bridges billions of years of evolutionary divergence and provides an example of an RNA structure-based translation initiation signal capable of operating in two domains of life.
Exaggerated Cap-Dependent Translation as a Mechanism for Corticostriatal Dysfunction in Fragile X Syndrome Model Mice

Science.gov (United States)

2016-10-01

Gordon Research Conference “Fragile X and Autism-Related Disorders”. Vermont, USA. 2) NCCR Synapsy “The Neurobiology of Mental Health ...and repetitive/perseverative behaviours displayed by FXS model mice are reversed by novel cap-dependent translation inhibitors...graduate student Person months worked: 3 cal mos Contribution to project: perform experiments and analyze data Name: Jonathan
Crystallization and preliminary crystallographic studies of the W2 domain of Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein

International Nuclear Information System (INIS)

Zhao, Hui; Wang, Hong; Liu, Huihui; Teng, Maikun; Li, Xu

2012-01-01

The crystallization and preliminary crystallographic studies of the carboxy-terminal domain of D. melanogaster eukaryotic translation initiation factor 5C domain-containing protein are reported. The Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein (ECP) is composed of two independently folded domains which belong to the basic leucine-zipper and W2 domain-containing protein (BZW) family. Based on the sequence similarity between the C-terminal W2 domain of ECP and some eukaryotic translation initiation factors (such as eIF2B∊, eIF4γ, eIF5 etc.), ECP has been speculated to participate in the translation initiation process. Structural information on the C-terminal W2 domain of ECP would be helpful in understanding the specific cellular function of this protein. Here, the W2 domain of ECP was expressed and crystallized. Crystals grown by the hanging-drop vapour-diffusion method diffracted to 2.70 Å resolution and belonged to space group I4, with unit-cell parameters a = b = 81.05, c = 57.44 Å. The Matthews coefficient suggested that there was one molecule per asymmetric unit in the crystal
RACK1-mediated translation control promotes liver fibrogenesis

Energy Technology Data Exchange (ETDEWEB)

Liu, Min; Peng, Peike; Wang, Jiajun [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Wang, Lan; Duan, Fangfang [Institute of Biomedical Science, Fudan University, Shanghai 200032 (China); Jia, Dongwei, E-mail: jiadongwei@fudan.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Ruan, Yuanyuan, E-mail: yuanyuanruan@fudan.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Institute of Biomedical Science, Fudan University, Shanghai 200032 (China)

2015-07-31

Activation of quiescent hepatic stellate cells (HSCs) is the central event of liver fibrosis. The translational machinery is an optimized molecular network that affects cellular homoeostasis and diseases, whereas the role of protein translation in HSCs activation and liver fibrosis is little defined. Our previous report suggests that up-regulation of receptor for activated C-kinase 1(RACK1) in HSCs is critical for liver fibrogenesis. In this study, we found that RACK1 promoted macrophage conditioned medium (MCM)-induced assembly of eIF4F and phosphorylation of eIF4E in primary HSCs. RACK1 enhanced the translation and expression of pro-fibrogenic factors collagen 1α1, snail and cyclin E1 induced by MCM. Administration of PP242 or knock-down of eIF4E suppressed RACK1-stimulated collagen 1α1 production, proliferation and migration in primary HSCs. In addition, depletion of eIF4E attenuated thioacetamide (TAA)-induced liver fibrosis in vivo. Our data suggest that RACK1-mediated stimulation of cap-dependent translation plays crucial roles in HSCs activation and liver fibrogenesis, and targeting translation initiation could be a promising strategy for the treatment of liver fibrosis. - Highlights: • RACK1 induces the assembly of eIF4F and phosphorylation of eIF4E in primary HSCs. • RACK1 stimulates the translation of collagen 1α1, snail and cyclin E1 in HSCs. • RACK1 promotes HSCs activation via cap-mediated translation. • Depletion of eIF4E suppresses liver fibrogenesis in vivo.

RACK1-mediated translation control promotes liver fibrogenesis

International Nuclear Information System (INIS)

Liu, Min; Peng, Peike; Wang, Jiajun; Wang, Lan; Duan, Fangfang; Jia, Dongwei; Ruan, Yuanyuan; Gu, Jianxin

2015-01-01

Activation of quiescent hepatic stellate cells (HSCs) is the central event of liver fibrosis. The translational machinery is an optimized molecular network that affects cellular homoeostasis and diseases, whereas the role of protein translation in HSCs activation and liver fibrosis is little defined. Our previous report suggests that up-regulation of receptor for activated C-kinase 1(RACK1) in HSCs is critical for liver fibrogenesis. In this study, we found that RACK1 promoted macrophage conditioned medium (MCM)-induced assembly of eIF4F and phosphorylation of eIF4E in primary HSCs. RACK1 enhanced the translation and expression of pro-fibrogenic factors collagen 1α1, snail and cyclin E1 induced by MCM. Administration of PP242 or knock-down of eIF4E suppressed RACK1-stimulated collagen 1α1 production, proliferation and migration in primary HSCs. In addition, depletion of eIF4E attenuated thioacetamide (TAA)-induced liver fibrosis in vivo. Our data suggest that RACK1-mediated stimulation of cap-dependent translation plays crucial roles in HSCs activation and liver fibrogenesis, and targeting translation initiation could be a promising strategy for the treatment of liver fibrosis. - Highlights: • RACK1 induces the assembly of eIF4F and phosphorylation of eIF4E in primary HSCs. • RACK1 stimulates the translation of collagen 1α1, snail and cyclin E1 in HSCs. • RACK1 promotes HSCs activation via cap-mediated translation. • Depletion of eIF4E suppresses liver fibrogenesis in vivo
Lariat capping as a tool to manipulate the 5' end of individual yeast mRNA species in vivo

DEFF Research Database (Denmark)

Krogh, Nicolai; Pietschmann, Max; Schmid, Manfred

2017-01-01

The 5' cap structure of eukaryotic mRNA is critical for its processing, transport, translation, and stability. The many functions of the cap and the fact that most, if not all, mRNA carries the same type of cap makes it difficult to analyze cap function in vivo at individual steps of gene...... in the budding yeast Saccharomyces cerevisiae presumably without cofactors and that lariat capping occurs cotranscriptionally. The lariat-capped reporter mRNA is efficiently exported to the cytoplasm where it is found to be oligoadenylated and evenly distributed. Both the oligoadenylated form and a lariat......-capped mRNA with a templated poly(A) tail translates poorly, underlining the critical importance of the m(7)G cap in translation. Finally, the lariat-capped RNA exhibits a threefold longer half-life compared to its m(7)G-capped counterpart, consistent with a key role for the m(7)G cap in mRNA turnover. Our...
HuR and Ago2 Bind the Internal Ribosome Entry Site of Enterovirus 71 and Promote Virus Translation and Replication.

Directory of Open Access Journals (Sweden)

Jing-Yi Lin

Full Text Available EV71 (enterovirus 71 RNA contains an internal ribosomal entry site (IRES that directs cap-independent initiation of translation. IRES-dependent translation requires the host's translation initiation factors and IRES-associated trans-acting factors (ITAFs. We reported recently that mRNA decay factor AUF1 is a negative-acting ITAF that binds IRES stem-loop II. We also reported that the small RNA-processing enzyme Dicer produces at least four small RNAs (vsRNAs from the EV71 IRES. One of these, vsRNA1, derived from IRES stem-loop II, reduces IRES activity and virus replication. Since its mechanism of action is unknown, we hypothesized that it might control association of ITAFs with the IRES. Here, we identified the mRNA stability factor HuR and the RISC subunit Argonaute 2 (Ago2 as two ITAFs that bind stem-loop II. In contrast to AUF1, HuR and Ago2 promote EV71 IRES activity and virus replication. In vitro RNA-binding assays revealed that vsRNA1 can alter association of Ago2, HuR, and AUF1 with stem-loop II. This presents a possible mechanism by which vsRNA1 could control viral translation and replication.
Internal and overall motions of the translation factor eIF4E: Cap binding and insertion in a CHAPS detergent micelle

International Nuclear Information System (INIS)

McGuire, Abigail Manson; Matsuo, Hiroshi; Wagner, Gerhard

1998-01-01

The mRNA cap-binding protein eIF4E is the limiting factor in the eIF4F translation initiation complex, which mediates the binding of the 40S ribosome to the mRNA. 15 N relaxation studies have been used to characterize the backbone dynamics of deuterated eIF4E in a CHAPS micelle for the apoprotein, the m 7 GDP-bound form, and the dinucleotide (m 7 GpppA)-bound form, as well as for CHAPS-free eIF4E. Large differences in overall correlation time between the CHAPS-free form (11.8 ns) and samples containing different concentrations of CHAPS (15.9-19.4 ns) indicate that eIF4E is embedded in a large micelle in the presence of CHAPS, with a total molecular weight in the range of 40-60 kDa. CHAPS seems to restrict the mobility of the a2-b3 and a4-b5 loops which are thought to be embedded in the micelle. No significant changes in overall mobility were seen between the m 7 GDP-bound form, the m 7 GpppA-bound form, and the apoprotein. Amide hydrogen exchange data indicate the presence of slowly exchanging amides in two surface-exposed helices (a2 and a4), as well as the a4-b5 loop, indicating protection by the CHAPS micelle. The micelle covers the convex side of the protein away from the cap-binding site
Identification of evolutionarily conserved non-AUG-initiated N-terminal extensions in human coding sequences.

LENUS (Irish Health Repository)

Ivanov, Ivaylo P

2011-05-01

In eukaryotes, it is generally assumed that translation initiation occurs at the AUG codon closest to the messenger RNA 5\\' cap. However, in certain cases, initiation can occur at codons differing from AUG by a single nucleotide, especially the codons CUG, UUG, GUG, ACG, AUA and AUU. While non-AUG initiation has been experimentally verified for a handful of human genes, the full extent to which this phenomenon is utilized--both for increased coding capacity and potentially also for novel regulatory mechanisms--remains unclear. To address this issue, and hence to improve the quality of existing coding sequence annotations, we developed a methodology based on phylogenetic analysis of predicted 5\\' untranslated regions from orthologous genes. We use evolutionary signatures of protein-coding sequences as an indicator of translation initiation upstream of annotated coding sequences. Our search identified novel conserved potential non-AUG-initiated N-terminal extensions in 42 human genes including VANGL2, FGFR1, KCNN4, TRPV6, HDGF, CITED2, EIF4G3 and NTF3, and also affirmed the conservation of known non-AUG-initiated extensions in 17 other genes. In several instances, we have been able to obtain independent experimental evidence of the expression of non-AUG-initiated products from the previously published literature and ribosome profiling data.
Enzymatic synthesis of RNAs capped with nucleotide analogues reveals the molecular basis for substrate selectivity of RNA capping enzyme: impacts on RNA metabolism.

Directory of Open Access Journals (Sweden)

Moheshwarnath Issur

Full Text Available RNA cap binding proteins have evolved to specifically bind to the N7-methyl guanosine cap structure found at the 5' ends of eukaryotic mRNAs. The specificity of RNA capping enzymes towards GTP for the synthesis of this structure is therefore crucial for mRNA metabolism. The fact that ribavirin triphosphate was described as a substrate of a viral RNA capping enzyme, raised the possibility that RNAs capped with nucleotide analogues could be generated in cellulo. Owing to the fact that this prospect potentially has wide pharmacological implications, we decided to investigate whether the active site of the model Paramecium bursaria Chlorella virus-1 RNA capping enzyme was flexible enough to accommodate various purine analogues. Using this approach, we identified several key structural determinants at each step of the RNA capping reaction and generated RNAs harboring various different cap analogues. Moreover, we monitored the binding affinity of these novel capped RNAs to the eIF4E protein and evaluated their translational properties in cellulo. Overall, this study establishes a molecular rationale for the specific selection of GTP over other NTPs by RNA capping enzyme It also demonstrates that RNAs can be enzymatically capped with certain purine nucleotide analogs, and it also describes the impacts of modified RNA caps on specific steps involved in mRNA metabolism. For instance, our results indicate that the N7-methyl group of the classical N7-methyl guanosine cap is not always indispensable for binding to eIF4E and subsequently for translation when compensatory modifications are present on the capped residue. Overall, these findings have important implications for our understanding of the molecular determinants involved in both RNA capping and RNA metabolism.
Regulation of Translation Initiation under Biotic and Abiotic Stresses

Directory of Open Access Journals (Sweden)

Ana B. Castro-Sanz

2013-02-01

Full Text Available Plants have developed versatile strategies to deal with the great variety of challenging conditions they are exposed to. Among them, the regulation of translation is a common target to finely modulate gene expression both under biotic and abiotic stress situations. Upon environmental challenges, translation is regulated to reduce the consumption of energy and to selectively synthesize proteins involved in the proper establishment of the tolerance response. In the case of viral infections, the situation is more complex, as viruses have evolved unconventional mechanisms to regulate translation in order to ensure the production of the viral encoded proteins using the plant machinery. Although the final purpose is different, in some cases, both plants and viruses share common mechanisms to modulate translation. In others, the mechanisms leading to the control of translation are viral- or stress-specific. In this paper, we review the different mechanisms involved in the regulation of translation initiation under virus infection and under environmental stress in plants. In addition, we describe the main features within the viral RNAs and the cellular mRNAs that promote their selective translation in plants undergoing biotic and abiotic stress situations.
The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5): Development and initial psychometric evaluation in military veterans.

Science.gov (United States)

Weathers, Frank W; Bovin, Michelle J; Lee, Daniel J; Sloan, Denise M; Schnurr, Paula P; Kaloupek, Danny G; Keane, Terence M; Marx, Brian P

2018-03-01

The Clinician-Administered PTSD Scale (CAPS) is an extensively validated and widely used structured diagnostic interview for posttraumatic stress disorder (PTSD). The CAPS was recently revised to correspond with PTSD criteria in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; American Psychiatric Association, 2013). This article describes the development of the CAPS for DSM-5 (CAPS-5) and presents the results of an initial psychometric evaluation of CAPS-5 scores in 2 samples of military veterans (Ns = 165 and 207). CAPS-5 diagnosis demonstrated strong interrater reliability (к = .78 to 1.00, depending on the scoring rule) and test-retest reliability (к = .83), as well as strong correspondence with a diagnosis based on the CAPS for DSM-IV (CAPS-IV; к = .84 when optimally calibrated). CAPS-5 total severity score demonstrated high internal consistency (α = .88) and interrater reliability (ICC = .91) and good test-retest reliability (ICC = .78). It also demonstrated good convergent validity with total severity score on the CAPS-IV (r = .83) and PTSD Checklist for DSM-5 (r = .66) and good discriminant validity with measures of anxiety, depression, somatization, functional impairment, psychopathy, and alcohol abuse (rs = .02 to .54). Overall, these results indicate that the CAPS-5 is a psychometrically sound measure of DSM-5 PTSD diagnosis and symptom severity. Importantly, the CAPS-5 strongly corresponds with the CAPS-IV, which suggests that backward compatibility with the CAPS-IV was maintained and that the CAPS-5 provides continuity in evidence-based assessment of PTSD in the transition from DSM-IV to DSM-5 criteria. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Modulation of Translation Initiation Efficiency in Classical Swine Fever Virus

DEFF Research Database (Denmark)

Friis, Martin Barfred; Rasmussen, Thomas Bruun; Belsham, Graham

2012-01-01

Modulation of translation initiation efficiency on classical swine fever virus (CSFV) RNA can be achieved by targeted mutations within the internal ribosome entry site (IRES). In this study, cDNAs corresponding to the wild type (wt) or mutant forms of the IRES of CSFV strain Paderborn were...... in vitro and electroporated into porcine PK15 cells. Rescued mutant viruses were obtained from RNAs that contained mutations within domain IIIf which retained more than 75% of wt translation efficiency. Sequencing of cDNA generated from these rescued viruses verified the maintenance of the introduced...... changes within the IRES. The growth characteristics of each rescued mutant virus were compared to that of the wt virus. It was shown that viable mutant viruses with reduced translation initiation efficiency can be designed and generated and that viruses containing mutations within domain IIIf of the IRES...
Initial studies using the RatCAP conscious animal PET tomograph

Energy Technology Data Exchange (ETDEWEB)

Woody, C. [Brookhaven National Laboratory, Upton, NY (United States)]. E-mail: woody@bnl.gov; Vaska, P. [Brookhaven National Laboratory, Upton, NY (United States); Schlyer, D. [Brookhaven National Laboratory, Upton, NY (United States); Pratte, J.-F. [Brookhaven National Laboratory, Upton, NY (United States); Junnarkar, S. [Brookhaven National Laboratory, Upton, NY (United States); Park, S.-J. [Brookhaven National Laboratory, Upton, NY (United States); Stoll, S. [Brookhaven National Laboratory, Upton, NY (United States); Purschke, M. [Brookhaven National Laboratory, Upton, NY (United States); Southekal, S. [Stony Brook University, Stony Brook, NY (United States); Kriplani, A. [Stony Brook University, Stony Brook, NY (United States); Krishnamoorthy, S. [Stony Brook University, Stony Brook, NY (United States); Maramraju, S. [Stony Brook University, Stony Brook, NY (United States); Lee, D. [Brookhaven National Laboratory, Upton, NY (United States); Schiffer, W. [Brookhaven National Laboratory, Upton, NY (United States); Dewey, S. [Brookhaven National Laboratory, Upton, NY (United States); Neill, J. [Long Island University, Brookville, NY (United States); Kandasamy, A. [Brookhaven National Laboratory, Upton, NY (United States); O' Connor, P. [Brookhaven National Laboratory, Upton, NY (United States); Radeka, V. [Brookhaven National Laboratory, Upton, NY (United States); Fontaine, R. [Sherbrooke University, Sherbrooke, Que. (Canada); Lecomte, R. [Sherbrooke University, Sherbrooke, Que. (Canada)

2007-02-01

The RatCAP is a small, head-mounted PET tomograph designed to image the brain of a conscious rat without the use of anesthesia. The detector is a complete, high-performance 3D tomograph consisting of a 3.8 cm inside-diameter ring containing 12 block detectors, each of which is comprised of a 4x8 array of 2.2x2.2x5 mm{sup 3} LSO crystals readout with a matching APD array and custom ASIC, and has a 1.8 cm axial field of view. Construction of the first working prototype detector has been completed and its performance characteristics have been measured. The results show an intrinsic spatial resolution of 2.1 mm, a time resolution of {approx}14 ns FWHM, and a sensitivity of 0.7% at an energy threshold of 150 keV. First preliminary images have been obtained using {sup 18}F-FDG and {sup 11}C-methamphetamine, which show comparable image quality to those obtained from a commercial MicroPET R4 scanner. Initial studies have also been carried out to study stress levels in rats wearing the RatCAP.
Initial studies using the RatCAP conscious animal PET tomograph

International Nuclear Information System (INIS)

Woody, C.; Vaska, P.; Schlyer, D.; Pratte, J.-F.; Junnarkar, S.; Park, S.-J.; Stoll, S.; Purschke, M.; Southekal, S.; Kriplani, A.; Krishnamoorthy, S.; Maramraju, S.; Lee, D.; Schiffer, W.; Dewey, S.; Neill, J.; Kandasamy, A.; O'Connor, P.; Radeka, V.; Fontaine, R.; Lecomte, R.

2007-01-01

The RatCAP is a small, head-mounted PET tomograph designed to image the brain of a conscious rat without the use of anesthesia. The detector is a complete, high-performance 3D tomograph consisting of a 3.8 cm inside-diameter ring containing 12 block detectors, each of which is comprised of a 4x8 array of 2.2x2.2x5 mm 3 LSO crystals readout with a matching APD array and custom ASIC, and has a 1.8 cm axial field of view. Construction of the first working prototype detector has been completed and its performance characteristics have been measured. The results show an intrinsic spatial resolution of 2.1 mm, a time resolution of ∼14 ns FWHM, and a sensitivity of 0.7% at an energy threshold of 150 keV. First preliminary images have been obtained using 18 F-FDG and 11 C-methamphetamine, which show comparable image quality to those obtained from a commercial MicroPET R4 scanner. Initial studies have also been carried out to study stress levels in rats wearing the RatCAP
Norovirus translation requires an interaction between the C Terminus of the genome-linked viral protein VPg and eukaryotic translation initiation factor 4G.

Science.gov (United States)

Chung, Liliane; Bailey, Dalan; Leen, Eoin N; Emmott, Edward P; Chaudhry, Yasmin; Roberts, Lisa O; Curry, Stephen; Locker, Nicolas; Goodfellow, Ian G

2014-08-01

Viruses have evolved a variety of mechanisms to usurp the host cell translation machinery to enable translation of the viral genome in the presence of high levels of cellular mRNAs. Noroviruses, a major cause of gastroenteritis in man, have evolved a mechanism that relies on the interaction of translation initiation factors with the virus-encoded VPg protein covalently linked to the 5' end of the viral RNA. To further characterize this novel mechanism of translation initiation, we have used proteomics to identify the components of the norovirus translation initiation factor complex. This approach revealed that VPg binds directly to the eIF4F complex, with a high affinity interaction occurring between VPg and eIF4G. Mutational analyses indicated that the C-terminal region of VPg is important for the VPg-eIF4G interaction; viruses with mutations that alter or disrupt this interaction are debilitated or non-viable. Our results shed new light on the unusual mechanisms of protein-directed translation initiation. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Protein synthesis in geostimulated root caps

Science.gov (United States)

Feldman, L. J.

1982-01-01

A study is presented of the processes occurring in the root cap of corn which are requisite for the formation of root cap inhibitor and which can be triggered or modulated by both light and gravity. The results of this study indicate the importance of protein synthesis for light-induced gravitropic bending in roots. Root caps in which protein synthesis is prevented are unable to induce downward bending. This suggests that light acts by stimulating proteins which are necessary for the translation of the gravitropic stimulus into a growth response (downward bending). The turnover of protein with time was also examined in order to determine whether light acts by stimulating the synthesis of unique proteins required for downward growth. It is found that auxin in combination with light allows for the translation of the gravitropic stimulus into a growth response at least in part through the modification of protein synthesis. It is concluded that unique proteins are stimulated by light and are involved in promoting the downward growth in roots which are responding to gravity.
The linker domain of poly(rC) binding protein 2 is a major determinant in poliovirus cap-independent translation.

Science.gov (United States)

Sean, Polen; Nguyen, Joseph H C; Semler, Bert L

2008-09-01

Poliovirus, a member of the enterovirus genus in the family Picornaviridae, is the causative agent of poliomyelitis. Translation of the viral genome is mediated through an internal ribosomal entry site (IRES) encoded within the 5' noncoding region (5' NCR). IRES elements are highly structured RNA sequences that facilitate the recruitment of ribosomes for translation. Previous studies have shown that binding of a cellular protein, poly(rC) binding protein 2 (PCBP2), to a major stem-loop structure in the genomic 5' NCR is necessary for the translation of picornaviruses containing type I IRES elements, including poliovirus, coxsackievirus, and human rhinovirus. PCBP1, an isoform that shares approximately 90% amino acid identity to PCBP2, cannot efficiently stimulate poliovirus IRES-mediated translation, most likely due to its reduced binding affinity to stem-loop IV within the poliovirus IRES. The primary differences between PCBP1 and PCBP2 are found in the so-called linker domain between the second and third K-homology (KH) domains of these proteins. We hypothesize that the linker region of PCBP2 augments binding to poliovirus stem-loop IV RNA. To test this hypothesis, we generated six PCBP1/PCBP2 chimeric proteins. The recombinant PCBP1/PCBP2 chimeric proteins were able to interact with poliovirus stem-loop I RNA and participate in protein-protein interactions. We demonstrated that the PCBP1/PCBP2 chimeric proteins with the PCBP2 linker, but not with the PCBP1 linker, were able to interact with poliovirus stem-loop IV RNA, and could subsequently stimulate poliovirus IRES-mediated translation. In addition, using a monoclonal anti-PCBP2 antibody (directed against the PCBP2 linker domain) in mobility shift assays, we showed that the PCBP2 linker domain modulates binding to poliovirus stem-loop IV RNA via a mechanism that is not inhibited by the antibody.
Mapping of p140Cap phosphorylation sites

DEFF Research Database (Denmark)

Repetto, Daniele; Aramu, Simona; Boeri Erba, Elisabetta

2013-01-01

phosphorylation and tunes its interactions with other regulatory molecules via post-translation modification. In this work, using mass spectrometry, we found that p140Cap is in vivo phosphorylated on tyrosine (Y) within the peptide GEGLpYADPYGLLHEGR (from now on referred to as EGLYA) as well as on three serine...... residues. Consistently, EGLYA has the highest score of in silico prediction of p140Cap phosphorylation. To further investigate the p140Cap function, we performed site specific mutagenesis on tyrosines inserted in EGLYA and EPLYA, a second sequence with the same highest score of phosphorylation. The mutant...
Complete motif analysis of sequence requirements for translation initiation at non-AUG start codons.

Science.gov (United States)

Diaz de Arce, Alexander J; Noderer, William L; Wang, Clifford L

2018-01-25

The initiation of mRNA translation from start codons other than AUG was previously believed to be rare and of relatively low impact. More recently, evidence has suggested that as much as half of all translation initiation utilizes non-AUG start codons, codons that deviate from AUG by a single base. Furthermore, non-AUG start codons have been shown to be involved in regulation of expression and disease etiology. Yet the ability to gauge expression based on the sequence of a translation initiation site (start codon and its flanking bases) has been limited. Here we have performed a comprehensive analysis of translation initiation sites that utilize non-AUG start codons. By combining genetic-reporter, cell-sorting, and high-throughput sequencing technologies, we have analyzed the expression associated with all possible variants of the -4 to +4 positions of non-AUG translation initiation site motifs. This complete motif analysis revealed that 1) with the right sequence context, certain non-AUG start codons can generate expression comparable to that of AUG start codons, 2) sequence context affects each non-AUG start codon differently, and 3) initiation at non-AUG start codons is highly sensitive to changes in the flanking sequences. Complete motif analysis has the potential to be a key tool for experimental and diagnostic genomics. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
Translation initiation factors eIF3 and HCR1 control translation termination and stop codon read-through in yeast cells

Czech Academy of Sciences Publication Activity Database

Beznosková, P.; Cuchalová, Lucie; Wagner, S.; Shoemaker, Ch. J.; Gunišová, S.; von der Haar, T.; Valášek, L. S.

2013-01-01

Roč. 9, č. 11 (2013), e1003962_1-e1003962_17 ISSN 1553-7404 Institutional support: RVO:61389013 Keywords : translation initiation * translation termination * eIF3 Subject RIV: CD - Macromolecular Chemistry Impact factor: 8.167, year: 2013
PERK Signal-Modulated Protein Translation Promotes the Survivability of Dengue 2 Virus-Infected Mosquito Cells and Extends Viral Replication.

Science.gov (United States)

Hou, Jiun-Nan; Chen, Tien-Huang; Chiang, Yi-Hsuan; Peng, Jing-Yun; Yang, Tsong-Han; Cheng, Chih-Chieh; Sofiyatun, Eny; Chiu, Cheng-Hsun; Chiang-Ni, Chuan; Chen, Wei-June

2017-09-20

Survival of mosquitoes from dengue virus (DENV) infection is a prerequisite of viral transmission to the host. This study aimed to see how mosquito cells can survive the infection during prosperous replication of the virus. In C6/36 cells, global protein translation was shut down after infection by DENV type 2 (DENV2). However, it returned to a normal level when infected cells were treated with an inhibitor of the protein kinase RNA (PKR)-like ER kinase (PERK) signaling pathway. Based on a 7-Methylguanosine 5'-triphosphate (m7GTP) pull-down assay, the eukaryotic translation initiation factor 4F (eIF4F) complex was also identified in DENV2-infected cells. This suggests that most mosquito proteins are synthesized via canonical cap-dependent translation. When the PERK signal pathway was inhibited, both accumulation of reactive oxygen species and changes in the mitochondrial membrane potential increased. This suggested that ER stress response was alleviated through the PERK-mediated shutdown of global proteins in DENV2-infected C6/36 cells. In the meantime, the activities of caspases-9 and -3 and the apoptosis-related cell death rate increased in C6/36 cells with PERK inhibition. This reflected that the PERK-signaling pathway is involved in determining cell survival, presumably by reducing DENV2-induced ER stress. Looking at the PERK downstream target, α-subunit of eukaryotic initiation factor 2 (eIF2α), an increased phosphorylation status was only shown in infected C6/36 cells. This indicated that recruitment of ribosome binding to the mRNA 5'-cap structure could have been impaired in cap-dependent translation. It turned out that shutdown of cellular protein translation resulted in a pro-survival effect on mosquito cells in response to DENV2 infection. As synthesis of viral proteins was not affected by the PERK signal pathway, an alternate mode other than cap-dependent translation may be utilized. This finding provides insights into elucidating how the PERK signal
Mixed messages: Re-initiation factors regulate translation of animal mRNAs

OpenAIRE

Obermayer, Benedikt; Rajewsky, Nikolaus

2014-01-01

When ribosomes encounter upstream open reading frames (uORFs) during scanning of the 5' untranslated region (5' UTR), translation of the downstream ORF requires re-initiation. In a recent paper in Nature, Schleich et al. describe metazoan factors which specifically promote re-initiation.
Nonreplicative RNA Recombination of an Animal Plus-Strand RNA Virus in the Absence of Efficient Translation of Viral Proteins

Science.gov (United States)

Kleine Büning, Maximiliane; Meyer, Denise; Austermann-Busch, Sophia; Roman-Sosa, Gleyder; Rümenapf, Tillmann

2017-01-01

RNA recombination is a major driving force for the evolution of RNA viruses and is significantly implicated in the adaptation of viruses to new hosts, changes of virulence, as well as in the emergence of new viruses including drug-resistant and escape mutants. However, the molecular details of recombination in animal RNA viruses are only poorly understood. In order to determine whether viral RNA recombination depends on translation of viral proteins, a nonreplicative recombination system was established which is based on cotransfection of cells with synthetic bovine viral diarrhea virus (family Flaviviridae) RNA genome fragments either lacking the internal ribosome entry site required for cap-independent translation or lacking almost the complete polyprotein coding region. The emergence of a number of recombinant viruses demonstrated that IRES-mediated translation of viral proteins is dispensable for efficient recombination and suggests that RNA recombination can occur in the absence of viral proteins. Analyses of 58 independently emerged viruses led to the detection of recombinant genomes with duplications, deletions and insertions in the 5′ terminal region of the open reading frame, leading to enlarged core fusion proteins detectable by Western blot analysis. This demonstrates a remarkable flexibility of the pestivirus core protein. Further experiments with capped and uncapped genome fragments containing a luciferase gene for monitoring the level of protein translation revealed that even a ∼1,000-fold enhancement of translation of viral proteins did not increase the frequency of RNA recombination. Taken together, this study highlights that nonreplicative RNA recombination does not require translation of viral proteins. PMID:28338950

Timelines of translational science: From technology initiation to FDA approval.

Directory of Open Access Journals (Sweden)

Laura M McNamee

Full Text Available While timelines for clinical development have been extensively studied, there is little data on the broader path from initiation of research on novel drug targets, to approval of drugs based on this research. We examined timelines of translational science for 138 drugs and biologicals approved by the FDA from 2010-2014 using an analytical model of technology maturation. Research on targets for 102 products exhibited a characteristic (S-curve maturation pattern with exponential growth between statistically defined technology initiation and established points. The median initiation was 1974, with a median of 25 years to the established point, 28 years to first clinical trials, and 36 years to FDA approval. No products were approved before the established point, and development timelines were significantly longer when the clinical trials began before this point (11.5 vs 8.5 years, p<0.0005. Technological maturation represents the longest stage of translation, and significantly impacts the efficiency of drug development.
Hon-yaku: a biology-driven Bayesian methodology for identifying translation initiation sites in prokaryotes

Directory of Open Access Journals (Sweden)

de Hoon Michiel JL

2007-02-01

Full Text Available Abstract Background Computational prediction methods are currently used to identify genes in prokaryote genomes. However, identification of the correct translation initiation sites remains a difficult task. Accurate translation initiation sites (TISs are important not only for the annotation of unknown proteins but also for the prediction of operons, promoters, and small non-coding RNA genes, as this typically makes use of the intergenic distance. A further problem is that most existing methods are optimized for Escherichia coli data sets; applying these methods to newly sequenced bacterial genomes may not result in an equivalent level of accuracy. Results Based on a biological representation of the translation process, we applied Bayesian statistics to create a score function for predicting translation initiation sites. In contrast to existing programs, our combination of methods uses supervised learning to optimally use the set of known translation initiation sites. We combined the Ribosome Binding Site (RBS sequence, the distance between the translation initiation site and the RBS sequence, the base composition of the start codon, the nucleotide composition (A-rich sequences following start codons, and the expected distribution of the protein length in a Bayesian scoring function. To further increase the prediction accuracy, we also took into account the operon orientation. The outcome of the procedure achieved a prediction accuracy of 93.2% in 858 E. coli genes from the EcoGene data set and 92.7% accuracy in a data set of 1243 Bacillus subtilis 'non-y' genes. We confirmed the performance in the GC-rich Gamma-Proteobacteria Herminiimonas arsenicoxydans, Pseudomonas aeruginosa, and Burkholderia pseudomallei K96243. Conclusion Hon-yaku, being based on a careful choice of elements important in translation, improved the prediction accuracy in B. subtilis data sets and other bacteria except for E. coli. We believe that most remaining
Translational control of aberrant stress responses as a hallmark of cancer.

Science.gov (United States)

El-Naggar, Amal M; Sorensen, Poul H

2018-04-01

Altered mRNA translational control is emerging as a critical factor in cancer development and progression. Targeting specific elements of the translational machinery, such as mTORC1 or eIF4E, is emerging as a new strategy for innovative cancer therapy. While translation of most mRNAs takes place through cap-dependent mechanisms, a sub-population of cellular mRNA species, particularly stress-inducible mRNAs with highly structured 5'-UTR regions, are primarily translated through cap-independent mechanisms. Intriguingly, many of these mRNAs encode proteins that are involved in tumour cell adaptation to microenvironmental stress, and thus linked to aggressive behaviour including tumour invasion and metastasis. This necessitates a rigorous search for links between microenvironmental stress and aggressive tumour phenotypes. Under stress, cells block global protein synthesis to preserve energy while maintaining selective synthesis of proteins that support cell survival. One highly conserved mechanism to regulate protein synthesis under cell stress is to sequester mRNAs into cytosolic aggregates called stress granules (SGs), where their translation is silenced. SGs confer survival advantages and chemotherapeutic resistance to tumour cells under stress. Recently, it has been shown that genetically blocking SG formation dramatically reduces tumour invasive and metastatic capacity in vivo. Therefore, targeting SG formation might represent a potential treatment strategy to block cancer metastasis. Here, we present the critical link between selective mRNA translation, stress adaptation, SGs, and tumour progression. Further, we also explain how deciphering mechanisms of selective mRNA translation occurs under cell stress holds great promise for the identification of new targets in the treatment of cancer. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland
Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells

Energy Technology Data Exchange (ETDEWEB)

Ge, Yuqing; Zhou, Fengbiao; Chen, Hong; Cui, Chunhong; Liu, Dan [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Li, Qiuping [Zhongshan Hospital of Fudan University, Shanghai 200032 (China); Yang, Zhiyuan; Wu, Guoqiang [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Sun, Shuhui [Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Gu, Jianxin [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Institutes of Biomedical Sciences of Fudan University, Shanghai 200032 (China); Wei, Yuanyan, E-mail: yywei@fudan.edu.cn [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Jiang, Jianhai, E-mail: jianhaijiang@fudan.edu.cn [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China)

2010-07-09

Sox2, a master transcription factor, contributes to the generation of induced pluripotent stem cells and plays significant roles in sustaining the self-renewal of neural stem cells and glioma-initiating cells. Understanding the functional differences of Sox2 between glioma-initiating cells and normal neural stem cells would contribute to therapeutic approach for treatment of brain tumors. Here, we first demonstrated that Sox2 could contribute to the self-renewal and proliferation of glioma-initiating cells. The following experiments showed that Sox2 was activated at translational level in a subset of human glioma-initiating cells compared with the normal neural stem cells. Further investigation revealed there was a positive correlation between Sox2 and eukaryotic initiation factor 4E (eIF4E) in glioma tissues. Down-regulation of eIF4E decreased Sox2 protein level without altering its mRNA level in glioma-initiating cells, indicating that Sox2 was activated by eIF4E at translational level. Furthermore, eIF4E was presumed to regulate the expression of Sox2 by its 5' untranslated region (5' UTR) sequence. Our results suggest that the eIF4E-Sox2 axis is a novel mechanism of unregulated self-renewal of glioma-initiating cells, providing a potential therapeutic target for glioma.
Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells

International Nuclear Information System (INIS)

Ge, Yuqing; Zhou, Fengbiao; Chen, Hong; Cui, Chunhong; Liu, Dan; Li, Qiuping; Yang, Zhiyuan; Wu, Guoqiang; Sun, Shuhui; Gu, Jianxin; Wei, Yuanyan; Jiang, Jianhai

2010-01-01

Sox2, a master transcription factor, contributes to the generation of induced pluripotent stem cells and plays significant roles in sustaining the self-renewal of neural stem cells and glioma-initiating cells. Understanding the functional differences of Sox2 between glioma-initiating cells and normal neural stem cells would contribute to therapeutic approach for treatment of brain tumors. Here, we first demonstrated that Sox2 could contribute to the self-renewal and proliferation of glioma-initiating cells. The following experiments showed that Sox2 was activated at translational level in a subset of human glioma-initiating cells compared with the normal neural stem cells. Further investigation revealed there was a positive correlation between Sox2 and eukaryotic initiation factor 4E (eIF4E) in glioma tissues. Down-regulation of eIF4E decreased Sox2 protein level without altering its mRNA level in glioma-initiating cells, indicating that Sox2 was activated by eIF4E at translational level. Furthermore, eIF4E was presumed to regulate the expression of Sox2 by its 5' untranslated region (5' UTR) sequence. Our results suggest that the eIF4E-Sox2 axis is a novel mechanism of unregulated self-renewal of glioma-initiating cells, providing a potential therapeutic target for glioma.
The Membrane-anchored Serine Protease Prostasin (CAP1/PRSS8) Supports Epidermal Development and Postnatal Homeostasis Independent of Its Enzymatic Activity

DEFF Research Database (Denmark)

Peters, Diane E; Szabo, Roman; Friis, Stine

2014-01-01

The membrane-anchored serine protease prostasin (CAP1/PRSS8) is part of a cell surface proteolytic cascade that is essential for epithelial barrier formation and homeostasis. Here, we report the surprising finding that prostasin executes these functions independent of its own enzymatic activity. ...
Nonreplicative RNA Recombination of an Animal Plus-Strand RNA Virus in the Absence of Efficient Translation of Viral Proteins.

Science.gov (United States)

Kleine Büning, Maximiliane; Meyer, Denise; Austermann-Busch, Sophia; Roman-Sosa, Gleyder; Rümenapf, Tillmann; Becher, Paul

2017-04-01

RNA recombination is a major driving force for the evolution of RNA viruses and is significantly implicated in the adaptation of viruses to new hosts, changes of virulence, as well as in the emergence of new viruses including drug-resistant and escape mutants. However, the molecular details of recombination in animal RNA viruses are only poorly understood. In order to determine whether viral RNA recombination depends on translation of viral proteins, a nonreplicative recombination system was established which is based on cotransfection of cells with synthetic bovine viral diarrhea virus (family Flaviviridae) RNA genome fragments either lacking the internal ribosome entry site required for cap-independent translation or lacking almost the complete polyprotein coding region. The emergence of a number of recombinant viruses demonstrated that IRES-mediated translation of viral proteins is dispensable for efficient recombination and suggests that RNA recombination can occur in the absence of viral proteins. Analyses of 58 independently emerged viruses led to the detection of recombinant genomes with duplications, deletions and insertions in the 5' terminal region of the open reading frame, leading to enlarged core fusion proteins detectable by Western blot analysis. This demonstrates a remarkable flexibility of the pestivirus core protein. Further experiments with capped and uncapped genome fragments containing a luciferase gene for monitoring the level of protein translation revealed that even a ∼1,000-fold enhancement of translation of viral proteins did not increase the frequency of RNA recombination. Taken together, this study highlights that nonreplicative RNA recombination does not require translation of viral proteins. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
The pharmaceutical vial capping process: Container closure systems, capping equipment, regulatory framework, and seal quality tests.

Science.gov (United States)

Mathaes, Roman; Mahler, Hanns-Christian; Buettiker, Jean-Pierre; Roehl, Holger; Lam, Philippe; Brown, Helen; Luemkemann, Joerg; Adler, Michael; Huwyler, Joerg; Streubel, Alexander; Mohl, Silke

2016-02-01

Parenteral drug products are protected by appropriate primary packaging to protect against environmental factors, including potential microbial contamination during shelf life duration. The most commonly used CCS configuration for parenteral drug products is the glass vial, sealed with a rubber stopper and an aluminum crimp cap. In combination with an adequately designed and controlled aseptic fill/finish processes, a well-designed and characterized capping process is indispensable to ensure product quality and integrity and to minimize rejections during the manufacturing process. In this review, the health authority requirements and expectations related to container closure system quality and container closure integrity are summarized. The pharmaceutical vial, the rubber stopper, and the crimp cap are described. Different capping techniques are critically compared: The most common capping equipment with a rotating capping plate produces the lowest amount of particle. The strength and challenges of methods to control the capping process are discussed. The residual seal force method can characterize the capping process independent of the used capping equipment or CCS. We analyze the root causes of several cosmetic defects associated with the vial capping process. Copyright © 2015 Elsevier B.V. All rights reserved.
Comparative genomic analysis of translation initiation mechanisms for genes lacking the Shine–Dalgarno sequence in prokaryotes

KAUST Repository

Nakagawa, So

2017-02-15

In prokaryotes, translation initiation is believed to occur through an interaction between the 3\\' tail of a 16S rRNA and a corresponding Shine-Dalgarno (SD) sequence in the 5\\' untranslated region (UTR) of an mRNA. However, some genes lack SD sequences (non-SD genes), and the fraction of non-SD genes in a genome varies depending on the prokaryotic species. To elucidate non-SD translation initiation mechanisms in prokaryotes from an evolutionary perspective, we statistically examined the nucleotide frequencies around the initiation codons in non-SD genes from 260 prokaryotes (235 bacteria and 25 archaea). We identified distinct nucleotide frequency biases upstream of the initiation codon in bacteria and archaea, likely because of the presence of leaderless mRNAs lacking a 5\\' UTR. Moreover, we observed overall similarities in the nucleotide patterns between upstream and downstream regions of the initiation codon in all examined phyla. Symmetric nucleotide frequency biases might facilitate translation initiation by preventing the formation of secondary structures around the initiation codon. These features are more prominent in species\\' genomes that harbor large fractions of non-SD sequences, suggesting that a reduced stability around the initiation codon is important for efficient translation initiation in prokaryotes.
Comparative genomic analysis of translation initiation mechanisms for genes lacking the Shine–Dalgarno sequence in prokaryotes

KAUST Repository

Nakagawa, So; Niimura, Yoshihito; Gojobori, Takashi

2017-01-01

In prokaryotes, translation initiation is believed to occur through an interaction between the 3' tail of a 16S rRNA and a corresponding Shine-Dalgarno (SD) sequence in the 5' untranslated region (UTR) of an mRNA. However, some genes lack SD sequences (non-SD genes), and the fraction of non-SD genes in a genome varies depending on the prokaryotic species. To elucidate non-SD translation initiation mechanisms in prokaryotes from an evolutionary perspective, we statistically examined the nucleotide frequencies around the initiation codons in non-SD genes from 260 prokaryotes (235 bacteria and 25 archaea). We identified distinct nucleotide frequency biases upstream of the initiation codon in bacteria and archaea, likely because of the presence of leaderless mRNAs lacking a 5' UTR. Moreover, we observed overall similarities in the nucleotide patterns between upstream and downstream regions of the initiation codon in all examined phyla. Symmetric nucleotide frequency biases might facilitate translation initiation by preventing the formation of secondary structures around the initiation codon. These features are more prominent in species' genomes that harbor large fractions of non-SD sequences, suggesting that a reduced stability around the initiation codon is important for efficient translation initiation in prokaryotes.
The distribution of synonymous codon choice in the translation initiation region of dengue virus.

Directory of Open Access Journals (Sweden)

Jian-hua Zhou

Full Text Available Dengue is the most common arthropod-borne viral (Arboviral illness in humans. The genetic features concerning the codon usage of dengue virus (DENV were analyzed by the relative synonymous codon usage, the effective number of codons and the codon adaptation index. The evolutionary distance between DENV and the natural hosts (Homo sapiens, Pan troglodytes, Aedes albopictus and Aedes aegypti was estimated by a novel formula. Finally, the synonymous codon usage preference for the translation initiation region of this virus was also analyzed. The result indicates that the general trend of the 59 synonymous codon usage of the four genotypes of DENV are similar to each other, and this pattern has no link with the geographic distribution of the virus. The effect of codon usage pattern of Aedes albopictus and Aedes aegypti on the formation of codon usage of DENV is stronger than that of the two primates. Turning to the codon usage preference of the translation initiation region of this virus, some codons pairing to low tRNA copy numbers in the two primates have a stronger tendency to exist in the translation initiation region than those in the open reading frame of DENV. Although DENV, like other RNA viruses, has a high mutation to adapt its hosts, the regulatory features about the synonymous codon usage have been 'branded' on the translation initiation region of this virus in order to hijack the translational mechanisms of the hosts.
The long non-coding RNA GAS5 cooperates with the eukaryotic translation initiation factor 4E to regulate c-Myc translation.

Directory of Open Access Journals (Sweden)

Guangzhen Hu

Full Text Available Long noncoding RNAs (lncRNAs are important regulators of transcription; however, their involvement in protein translation is not well known. Here we explored whether the lncRNA GAS5 is associated with translation initiation machinery and regulates translation. GAS5 was enriched with eukaryotic translation initiation factor-4E (eIF4E in an RNA-immunoprecipitation assay using lymphoma cell lines. We identified two RNA binding motifs within eIF4E protein and the deletion of each motif inhibited the binding of GAS5 with eIF4E. To confirm the role of GAS5 in translation regulation, GAS5 siRNA and in vitro transcribed GAS5 RNA were used to knock down or overexpress GAS5, respectively. GAS5 siRNA had no effect on global protein translation but did specifically increase c-Myc protein level without an effect on c-Myc mRNA. The mechanism of this increase in c-Myc protein was enhanced association of c-Myc mRNA with the polysome without any effect on protein stability. In contrast, overexpression of in vitro transcribed GAS5 RNA suppressed c-Myc protein without affecting c-Myc mRNA. Interestingly, GAS5 was found to be bound with c-Myc mRNA, suggesting that GAS5 regulates c-Myc translation through lncRNA-mRNA interaction. Our findings have uncovered a role of GAS5 lncRNA in translation regulation through its interactions with eIF4E and c-Myc mRNA.
Enterovirus 71 contains a type I IRES element that functions when eukaryotic initiation factor eIF4G is cleaved

International Nuclear Information System (INIS)

Thompson, Sunnie R.; Sarnow, Peter

2003-01-01

Human enterovirus 71 (EV71) is a member of the Enterovirus genus of the Picornaviridae family. Other members of this family utilize an unusual mechanism of translation initiation whereby ribosomes are recruited internally to the viral RNA by an internal ribosome site (IRES) located in their 5' noncoding regions (5' NCR). Using dicistronic reporter constructs, we demonstrate that the 5' NCRs of the 7423/MS/87 and BrCr strains of EV71 function as an IRES both in extracts and in cultured cells. Preincubation of translation extracts with purified coxsackievirus 2A protease cleaved elF4G, a component of the cap binding complex, resulting in a significant decrease in translation of capped mRNAs. In contrast, the translational efficiency of the EV71 IRES was enhanced under this condition, demonstrating that the EV71 IRES functions similar to other enterovirus IRES elements when components of the cap binding protein complex are cleaved. Finally, insertion of an upstream, out-of-frame start codon in the 5' NCR of the EV71 genome inhibited IRES activity, suggesting that EV71 can be classified as a type I IRES, in which ribosomes first bind upstream of the initiation codon and then scan the mRNA until an appropriate downstream AUG start codon is encountered and protein synthesis commences
Independence of Movement Preparation and Movement Initiation.

Science.gov (United States)

Haith, Adrian M; Pakpoor, Jina; Krakauer, John W

2016-03-09

Initiating a movement in response to a visual stimulus takes significantly longer than might be expected on the basis of neural transmission delays, but it is unclear why. In a visually guided reaching task, we forced human participants to move at lower-than-normal reaction times to test whether normal reaction times are strictly necessary for accurate movement. We found that participants were, in fact, capable of moving accurately ∼80 ms earlier than their reaction times would suggest. Reaction times thus include a seemingly unnecessary delay that accounts for approximately one-third of their duration. Close examination of participants' behavior in conventional reaction-time conditions revealed that they generated occasional, spontaneous errors in trials in which their reaction time was unusually short. The pattern of these errors could be well accounted for by a simple model in which the timing of movement initiation is independent of the timing of movement preparation. This independence provides an explanation for why reaction times are usually so sluggish: delaying the mean time of movement initiation relative to preparation reduces the risk that a movement will be initiated before it has been appropriately prepared. Our results suggest that preparation and initiation of movement are mechanistically independent and may have a distinct neural basis. The results also demonstrate that, even in strongly stimulus-driven tasks, presentation of a stimulus does not directly trigger a movement. Rather, the stimulus appears to trigger an internal decision whether to make a movement, reflecting a volitional rather than reactive mode of control. Copyright © 2016 the authors 0270-6474/16/363007-10$15.00/0.
MetWAMer: eukaryotic translation initiation site prediction

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Brendel Volker

2008-09-01

Full Text Available Abstract Background Translation initiation site (TIS identification is an important aspect of the gene annotation process, requisite for the accurate delineation of protein sequences from transcript data. We have developed the MetWAMer package for TIS prediction in eukaryotic open reading frames of non-viral origin. MetWAMer can be used as a stand-alone, third-party tool for post-processing gene structure annotations generated by external computational programs and/or pipelines, or directly integrated into gene structure prediction software implementations. Results MetWAMer currently implements five distinct methods for TIS prediction, the most accurate of which is a routine that combines weighted, signal-based translation initiation site scores and the contrast in coding potential of sequences flanking TISs using a perceptron. Also, our program implements clustering capabilities through use of the k-medoids algorithm, thereby enabling cluster-specific TIS parameter utilization. In practice, our static weight array matrix-based indexing method for parameter set lookup can be used with good results in data sets exhibiting moderate levels of 5'-complete coverage. Conclusion We demonstrate that improvements in statistically-based models for TIS prediction can be achieved by taking the class of each potential start-methionine into account pending certain testing conditions, and that our perceptron-based model is suitable for the TIS identification task. MetWAMer represents a well-documented, extensible, and freely available software system that can be readily re-trained for differing target applications and/or extended with existing and novel TIS prediction methods, to support further research efforts in this area.
Portable Language-Independent Adaptive Translation from OCR

National Research Council Canada - National Science Library

Natarajan, Prem

2008-01-01

.... The Multilingual Automatic Document Classification, Analysis and Translation (MADCAT) program will develop an end-to-end system to automatically translate handwritten and printed foreign documents into English with very high accuracy...
Modulation of Translation Initiation Efficiency in Classical Swine Fever Virus

DEFF Research Database (Denmark)

Friis, Martin Barfred; Rasmussen, Thomas Bruun; Belsham, Graham J.

Modulation of translation initiation efficiency on classical swine fever virus (CSFV) RNA can be achieved by targeted mutations within the internal ribosome entry site (IRES). In this study, the nucleotides 47 to 427, including the IRES region of the wt CSFV strain Paderborn, were amplified...... and inserted, under T7 promoter control, into mono- and dicistronic plasmids containing the reporter genes rLuc and fLuc. Mutant fragments of the IRES sequence were generated by overlap PCR and inserted into the reporter plasmids. To evaluate IRES functionality, translation of the rLUC was placed under...... viruses were obtained after one cell culture passage from constructs with more than 75 % translation efficiency compared to the wildtype IRES. cDNA was generated from these clones and sequenced to verify the maintenance of the changes in the IRES. These results show that full-length viable mutant viruses...
BARE retrotransposons are translated and replicated via distinct RNA pools.

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Wei Chang

Full Text Available The replication of Long Terminal Repeat (LTR retrotransposons, which can constitute over 80% of higher plant genomes, resembles that of retroviruses. A major question for retrotransposons and retroviruses is how the two conflicting roles of their transcripts, in translation and reverse transcription, are balanced. Here, we show that the BARE retrotransposon, despite its organization into just one open reading frame, produces three distinct classes of transcripts. One is capped, polyadenylated, and translated, but cannot be copied into cDNA. The second is not capped or polyadenylated, but is destined for packaging and ultimate reverse transcription. The third class is capped, polyadenylated, and spliced to favor production of a subgenomic RNA encoding only Gag, the protein forming virus-like particles. Moreover, the BARE2 subfamily, which cannot synthesize Gag and is parasitic on BARE1, does not produce the spliced sub-genomic RNA for translation but does make the replication competent transcripts, which are packaged into BARE1 particles. To our knowledge, this is first demonstration of distinct RNA pools for translation and transcription for any retrotransposon.
Enhancement of internal ribosome entry site-mediated translation and replication of hepatitis C virus by PD98059

International Nuclear Information System (INIS)

Murata, Takayuki; Hijikata, Makoto; Shimotohno, Kunitada

2005-01-01

Translation initiation of hepatitis C virus (HCV) occurs in an internal ribosome entry site (IRES)-dependent manner. We found that HCV IRES-dependent protein synthesis is enhanced by PD98059, an inhibitor of the extracellular signal-regulated kinase (ERK) signaling pathway, while cellular cap-dependent translation was relatively unaffected by the compound. Treatment of cells with PD98059 allowed for robust HCV replication following cellular incubation with HCV-positive serum. Though the molecular mechanism underlying IRES enhancement remains elusive, PD98059 is a potent accelerator of HCV RNA replication
Translation Initiation from Conserved Non-AUG Codons Provides Additional Layers of Regulation and Coding Capacity

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Ivaylo P. Ivanov

2017-06-01

Full Text Available Neurospora crassa cpc-1 and Saccharomyces cerevisiae GCN4 are homologs specifying transcription activators that drive the transcriptional response to amino acid limitation. The cpc-1 mRNA contains two upstream open reading frames (uORFs in its >700-nucleotide (nt 5′ leader, and its expression is controlled at the level of translation in response to amino acid starvation. We used N. crassa cell extracts and obtained data indicating that cpc-1 uORF1 and uORF2 are functionally analogous to GCN4 uORF1 and uORF4, respectively, in controlling translation. We also found that the 5′ region upstream of the main coding sequence of the cpc-1 mRNA extends for more than 700 nucleotides without any in-frame stop codon. For 100 cpc-1 homologs from Pezizomycotina and from selected Basidiomycota, 5′ conserved extensions of the CPC1 reading frame are also observed. Multiple non-AUG near-cognate codons (NCCs in the CPC1 reading frame upstream of uORF2, some deeply conserved, could potentially initiate translation. At least four NCCs initiated translation in vitro. In vivo data were consistent with initiation at NCCs to produce N-terminally extended N. crassa CPC1 isoforms. The pivotal role played by CPC1, combined with its translational regulation by uORFs and NCC utilization, underscores the emerging significance of noncanonical initiation events in controlling gene expression.

Characterization of a mimivirus RNA cap guanine-N2 methyltransferase.

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Benarroch, Delphine; Qiu, Zhicheng R; Schwer, Beate; Shuman, Stewart

2009-04-01

A 2,2,7-trimethylguanosine (TMG) cap is a signature feature of eukaryal snRNAs, telomerase RNAs, and trans-spliced nematode mRNAs. TMG and 2,7-dimethylguanosine (DMG) caps are also present on mRNAs of two species of alphaviruses (positive strand RNA viruses of the Togaviridae family). It is presently not known how viral mRNAs might acquire a hypermethylated cap. Mimivirus, a giant DNA virus that infects amoeba, encodes many putative enzymes and proteins implicated in RNA transactions, including the synthesis and capping of viral mRNAs and the promotion of cap-dependent translation. Here we report the identification, purification, and characterization of a mimivirus cap-specific guanine-N2 methyltransferase (MimiTgs), a monomeric enzyme that catalyzes a single round of methyl transfer from AdoMet to an m(7)G cap substrate to form a DMG cap product. MimiTgs, is apparently unable to convert a DMG cap to a TMG cap, and is thereby distinguished from the structurally homologous yeast and human Tgs1 enzymes. Nonetheless, we show genetically that MimiTgs is a true ortholog of Saccharomyces cerevisiae Tgs1. Our results hint that DMG caps can satisfy many of the functions of TMG caps in vivo. We speculate that DMG capping of mimivirus mRNAs might favor viral protein synthesis in the infected host.
Targeting the eIF4F translation initiation complex: a critical nexus for cancer development.

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Pelletier, Jerry; Graff, Jeremy; Ruggero, Davide; Sonenberg, Nahum

2015-01-15

Elevated protein synthesis is an important feature of many cancer cells and often arises as a consequence of increased signaling flux channeled to eukaryotic initiation factor 4F (eIF4F), the key regulator of the mRNA-ribosome recruitment phase of translation initiation. In many cellular and preclinical models of cancer, eIF4F deregulation results in changes in translational efficiency of specific mRNA classes. Importantly, many of these mRNAs code for proteins that potently regulate critical cellular processes, such as cell growth and proliferation, enhanced cell survival and cell migration that ultimately impinge on several hallmarks of cancer, including increased angiogenesis, deregulated growth control, enhanced cellular survival, epithelial-to-mesenchymal transition, invasion, and metastasis. By being positioned as the molecular nexus downstream of key oncogenic signaling pathways (e.g., Ras, PI3K/AKT/TOR, and MYC), eIF4F serves as a direct link between important steps in cancer development and translation initiation. Identification of mRNAs particularly responsive to elevated eIF4F activity that typifies tumorigenesis underscores the critical role of eIF4F in cancer and raises the exciting possibility of developing new-in-class small molecules targeting translation initiation as antineoplastic agents. ©2014 American Association for Cancer Research.
Aerosol delivery of Akt controls protein translation in the lungs of dual luciferase reporter mice.

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Tehrani, A M; Hwang, S-K; Kim, T-H; Cho, C-S; Hua, J; Nah, W-S; Kwon, J-T; Kim, J-S; Chang, S-H; Yu, K-N; Park, S-J; Bhandari, D R; Lee, K-H; An, G-H; Beck, G R; Cho, M-H

2007-03-01

Lung cancer has emerged as a leading cause of cancer death in the world; however, most of the current conventional therapies are not sufficiently effective in altering the progression of disease. Therefore, development of novel treatment approaches is needed. Although several genes and methods have been used for cancer gene therapy, a number of problems such as specificity, efficacy and toxicity reduce their application. This has led to re-emergence of aerosol gene delivery as a noninvasive method for lung cancer treatment. In this study, nano-sized glucosylated polyethyleneimine (GPEI) was used as a gene delivery carrier to investigate the effects of Akt wild type (WT) and kinase deficient (KD) on Akt-related signaling pathways and protein translation in the lungs of CMV- LucR-cMyc-IRES-LucF dual reporter mice. These mice are a powerful tool for the discrimination between cap-dependent/-independent protein translation. Aerosols containing self-assembled nano-sized GPEI/Akt WT or GPEI/Akt KD were delivered into the lungs of reporter mice through nose-only-inhalation-chamber with the aid of nebulizer. Aerosol delivery of Akt WT caused the increase of protein expression levels of Akt-related signals, whereas aerosol delivery of Akt KD did not. Furthermore, dual luciferase activity assay showed that aerosol delivery of Akt WT enhanced cap-dependent protein translation, whereas a reduction in cap-dependent protein translation by Akt KD was observed. Our results clearly showed that targeting Akt may be a good strategy for prevention as well as treatment of lung cancer. These studies suggest that our aerosol delivery is compatible for in vivo gene delivery which could be used as a noninvasive gene therapy in the future.
Translation initiation in bacterial polysomes through ribosome loading on a standby site on a highly translated mRNA

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Andreeva, Irena

2018-01-01

During translation, consecutive ribosomes load on an mRNA and form a polysome. The first ribosome binds to a single-stranded mRNA region and moves toward the start codon, unwinding potential mRNA structures on the way. In contrast, the following ribosomes can dock at the start codon only when the first ribosome has vacated the initiation site. Here we show that loading of the second ribosome on a natural 38-nt-long 5′ untranslated region of lpp mRNA, which codes for the outer membrane lipoprotein from Escherichia coli, takes place before the leading ribosome has moved away from the start codon. The rapid formation of this standby complex depends on the presence of ribosomal proteins S1/S2 in the leading ribosome. The early recruitment of the second ribosome to the standby site before translation by the leading ribosome and the tight coupling between translation elongation by the first ribosome and the accommodation of the second ribosome can contribute to high translational efficiency of the lpp mRNA. PMID:29632209
The Innovative Medicines Initiative moves translational immunology forward.

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Goldman, Michel; Wittelsberger, Angela; De Magistris, Maria-Teresa

2013-02-01

The Innovative Medicines Initiative (IMI) was established in 2008 as a public-private partnership between the European Union and the European Federation of Pharmaceutical Industries and Associations with the mission to promote the development of novel therapies through collaborative efforts based on the concept of pre-competitive research. Several consortia supported by IMI are dedicated to immuno-inflammatory disorders, immune-based biopharmaceuticals and vaccines. Herein, we present the key principles underlying IMI, briefly review the status of projects related to translational immunology, and present future topics of interest to immunologists.
Structural modelling and phylogenetic analyses of PgeIF4A2 (Eukaryotic translation initiation factor) from Pennisetum glaucum reveal signature motifs with a role in stress tolerance and development.

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Agarwal, Aakrati; Mudgil, Yashwanti; Pandey, Saurabh; Fartyal, Dhirendra; Reddy, Malireddy K

2016-01-01

Eukaryotic translation initiation factor 4A (eIF4A) is an indispensable component of the translation machinery and also play a role in developmental processes and stress alleviation in plants and animals. Different eIF4A isoforms are present in the cytosol of the cell, namely, eIF4A1, eIF4A2, and eIF4A3 and their expression is tightly regulated in cap-dependent translation. We revealed the structural model of PgeIF4A2 protein using the crystal structure of Homo sapiens eIF4A3 (PDB ID: 2J0S) as template by Modeller 9.12. The resultant PgeIF4A2 model structure was refined by PROCHECK, ProSA, Verify3D and RMSD that showed the model structure is reliable with 77 % amino acid sequence identity with template. Investigation revealed two conserved signatures for ATP-dependent RNA Helicase DEAD-box conserved site (VLDEADEML) and RNA helicase DEAD-box type, Q-motif in sheet-turn-helix and α-helical region respectively. All these conserved motifs are responsible for response during developmental stages and stress tolerance in plants.
Experimental Analysis of Mimivirus Translation Initiation Factor 4a Reveals Its Importance in Viral Protein Translation during Infection of Acanthamoeba polyphaga.

Science.gov (United States)

Bekliz, Meriem; Azza, Said; Seligmann, Hervé; Decloquement, Philippe; Raoult, Didier; La Scola, Bernard

2018-05-15

The Acanthamoeba polyphaga mimivirus is the first giant virus ever described, with a 1.2-Mb genome which encodes 979 proteins, including central components of the translation apparatus. One of these proteins, R458, was predicted to initiate translation, although its specific role remains unknown. We silenced the R458 gene using small interfering RNA (siRNA) and compared levels of viral fitness and protein expression in silenced versus wild-type mimivirus. Silencing decreased the growth rate, but viral particle production at the end of the viral cycle was unaffected. A comparative proteomic approach using two-dimensional difference-in-gel electrophoresis (2D-DIGE) revealed deregulation of the expression of 32 proteins in silenced mimivirus, which were defined as up- or downregulated. Besides revealing proteins with unknown functions, silencing R458 also revealed deregulation in proteins associated with viral particle structures, transcriptional machinery, oxidative pathways, modification of proteins/lipids, and DNA topology/repair. Most of these proteins belong to genes transcribed at the end of the viral cycle. Overall, our data suggest that the R458 protein regulates the expression of mimivirus proteins and, thus, that mimivirus translational proteins may not be strictly redundant in relation to those from the amoeba host. As is the case for eukaryotic initiation factor 4a (eIF4a), the R458 protein is the prototypical member of the ATP-dependent DEAD box RNA helicase mechanism. We suggest that the R458 protein is required to unwind the secondary structures at the 5' ends of mRNAs and to bind the mRNA to the ribosome, making it possible to scan for the start codon. These data are the first experimental evidence of mimivirus translation-related genes, predicted to initiate protein biosynthesis. IMPORTANCE The presence in the genome of a mimivirus of genes coding for many translational processes, with the exception of ribosome constituents, has been the subject of
The internal initiation of translation in bovine viral diarrhea virus RNA depends on the presence of an RNA pseudoknot upstream of the initiation codon.

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Moes, Lorin; Wirth, Manfred

2007-11-22

Bovine viral diarrhea virus (BVDV) is the prototype representative of the pestivirus genus in the Flaviviridae family. It has been shown that the initiation of translation of BVDV RNA occurs by an internal ribosome entry mechanism mediated by the 5' untranslated region of the viral RNA 1. The 5' and 3' boundaries of the IRES of the cytopathic BVDV NADL have been mapped and it has been suggested that the IRES extends into the coding of the BVDV polyprotein 2. A putative pseudoknot structure has been recognized in the BVDV 5'UTR in close proximity to the AUG start codon. A pseudoknot structure is characteristic for flavivirus IRESes and in the case of the closely related classical swine fever virus (CSFV) and the more distantly related Hepatitis C virus (HCV) pseudoknot function in translation has been demonstrated. To characterize the BVDV IRESes in detail, we studied the BVDV translational initiation by transfection of dicistronic expression plasmids into mammalian cells. A region coding for the amino terminus of the BVDV SD-1 polyprotein contributes considerably to efficient initiation of translation. The translation efficiency mediated by the IRES of BVDV strains NADL and SD-1 approximates the poliovirus type I IRES directed translation in BHK cells. Compared to the poliovirus IRES increased expression levels are mediated by the BVDV IRES of strain SD-1 in murine cell lines, while lower levels are observed in human cell lines. Site directed mutagenesis revealed that a RNA pseudoknot upstream of the initiator AUG is an important structural element for IRES function. Mutants with impaired ability to base pair in stem I or II lost their translational activity. In mutants with repaired base pairing either in stem 1 or in stem 2 full translational activity was restored. Thus, the BVDV IRES translation is dependent on the pseudoknot integrity. These features of the pestivirus IRES are reminiscent of those of the classical swine fever virus, a pestivirus, and the
The internal initiation of translation in bovine viral diarrhea virus RNA depends on the presence of an RNA pseudoknot upstream of the initiation codon

Directory of Open Access Journals (Sweden)

Moes Lorin

2007-11-01

Full Text Available Abstract Background Bovine viral diarrhea virus (BVDV is the prototype representative of the pestivirus genus in the Flaviviridae family. It has been shown that the initiation of translation of BVDV RNA occurs by an internal ribosome entry mechanism mediated by the 5' untranslated region of the viral RNA 1. The 5' and 3' boundaries of the IRES of the cytopathic BVDV NADL have been mapped and it has been suggested that the IRES extends into the coding of the BVDV polyprotein 2. A putative pseudoknot structure has been recognized in the BVDV 5'UTR in close proximity to the AUG start codon. A pseudoknot structure is characteristic for flavivirus IRESes and in the case of the closely related classical swine fever virus (CSFV and the more distantly related Hepatitis C virus (HCV pseudoknot function in translation has been demonstrated. Results To characterize the BVDV IRESes in detail, we studied the BVDV translational initiation by transfection of dicistronic expression plasmids into mammalian cells. A region coding for the amino terminus of the BVDV SD-1 polyprotein contributes considerably to efficient initiation of translation. The translation efficiency mediated by the IRES of BVDV strains NADL and SD-1 approximates the poliovirus type I IRES directed translation in BHK cells. Compared to the poliovirus IRES increased expression levels are mediated by the BVDV IRES of strain SD-1 in murine cell lines, while lower levels are observed in human cell lines. Site directed mutagenesis revealed that a RNA pseudoknot upstream of the initiator AUG is an important structural element for IRES function. Mutants with impaired ability to base pair in stem I or II lost their translational activity. In mutants with repaired base pairing either in stem 1 or in stem 2 full translational activity was restored. Thus, the BVDV IRES translation is dependent on the pseudoknot integrity. These features of the pestivirus IRES are reminiscent of those of the classical
A set of ligation-independent in vitro translation vectors for eukaryotic protein production

Directory of Open Access Journals (Sweden)

Endo Yaeta

2008-03-01

Full Text Available Abstract Background The last decade has brought the renaissance of protein studies and accelerated the development of high-throughput methods in all aspects of proteomics. Presently, most protein synthesis systems exploit the capacity of living cells to translate proteins, but their application is limited by several factors. A more flexible alternative protein production method is the cell-free in vitro protein translation. Currently available in vitro translation systems are suitable for high-throughput robotic protein production, fulfilling the requirements of proteomics studies. Wheat germ extract based in vitro translation system is likely the most promising method, since numerous eukaryotic proteins can be cost-efficiently synthesized in their native folded form. Although currently available vectors for wheat embryo in vitro translation systems ensure high productivity, they do not meet the requirements of state-of-the-art proteomics. Target genes have to be inserted using restriction endonucleases and the plasmids do not encode cleavable affinity purification tags. Results We designed four ligation independent cloning (LIC vectors for wheat germ extract based in vitro protein translation. In these constructs, the RNA transcription is driven by T7 or SP6 phage polymerase and two TEV protease cleavable affinity tags can be added to aid protein purification. To evaluate our improved vectors, a plant mitogen activated protein kinase was cloned in all four constructs. Purification of this eukaryotic protein kinase demonstrated that all constructs functioned as intended: insertion of PCR fragment by LIC worked efficiently, affinity purification of translated proteins by GST-Sepharose or MagneHis particles resulted in high purity kinase, and the affinity tags could efficiently be removed under different reaction conditions. Furthermore, high in vitro kinase activity testified of proper folding of the purified protein. Conclusion Four newly
PTENα, a PTEN isoform translated through alternative initiation, regulates mitochondrial function and energy metabolism.

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Liang, Hui; He, Shiming; Yang, Jingyi; Jia, Xinying; Wang, Pan; Chen, Xi; Zhang, Zhong; Zou, Xiajuan; McNutt, Michael A; Shen, Wen Hong; Yin, Yuxin

2014-05-06

PTEN is one of the most frequently mutated genes in human cancer. It is known that PTEN has a wide range of biological functions beyond tumor suppression. Here, we report that PTENα, an N-terminally extended form of PTEN, functions in mitochondrial metabolism. Translation of PTENα is initiated from a CUG codon upstream of and in-frame with the coding region of canonical PTEN. Eukaryotic translation initiation factor 2A (eIF2A) controls PTENα translation, which requires a CUG-centered palindromic motif. We show that PTENα induces cytochrome c oxidase activity and ATP production in mitochondria. TALEN-mediated somatic deletion of PTENα impairs mitochondrial respiratory chain function. PTENα interacts with canonical PTEN to increase PINK1 protein levels and promote energy production. Our studies demonstrate the importance of eIF2A-mediated alternative translation for generation of protein diversity in eukaryotic systems and provide insights into the mechanism by which the PTEN family is involved in multiple cellular processes. Copyright © 2014 Elsevier Inc. All rights reserved.
Catastrophic antiphospholipid syndrome (CAPS): Descriptive analysis of 500 patients from the International CAPS Registry.

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Rodríguez-Pintó, Ignasi; Moitinho, Marta; Santacreu, Irene; Shoenfeld, Yehuda; Erkan, Doruk; Espinosa, Gerard; Cervera, Ricard

2016-12-01

To analyze the clinical and immunologic manifestations of patients with catastrophic antiphospholipid syndrome (CAPS) from the "CAPS Registry". The demographic, clinical and serological features of 500 patients included in the website-based "CAPS Registry" were analyzed. Frequency distribution and measures of central tendency were used to describe the cohort. Comparison between groups regarding qualitative variables was undertaken by chi-square or Fisher exact test while T-test for independent variables was used to compare groups regarding continuous variables. 500 patients (female: 343 [69%]; mean age 38±17) accounting for 522 episodes of CAPS were included in the analysis. Forty percent of patients had an associated autoimmune disease, mainly systemic lupus erythematosus (SLE) (75%). The majority of CAPS episodes were triggered by a precipitating factor (65%), mostly infections (49%). Clinically, CAPS was characterized by several organ involvement affecting kidneys (73%), lungs (60%), brain (56%), heart (50%), and skin (47%). Lupus anticoagulant, IgG anticardiolipin and IgG anti-β2-glycprotein antibodies were the most often implicated antiphospholipid antibodies (83%, 81% and 78% respectively). Mortality accounted for 37% of episodes of CAPS. Several clinical differences could be observed based on the age of presentation and its association to SLE. Those cases triggered by a malignancy tended to occur in older patients, while CAPS episodes in young patients were associated with an infectious trigger and peripheral vessels involvement. Additionally, CAPS associated with SLE were more likely to have severe cardiac and brain involvement leading to a higher mortality (48%). Although the presentation of CAPS is characterized by multiorgan thrombosis and failure, clinical differences among patients exist based on age and underlying chronic diseases, e.g. malignancy and SLE. Copyright © 2016 Elsevier B.V. All rights reserved.
Designing Course An Initial Approach To Translation Teaching

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Roswani Siregar

2017-09-01

Full Text Available Along with the human history translation is the sustainable communication tool among the cultures to preserve this knowledge from generation to generations. Undoubtedly both translation plays a very important role in an increasingly globalized world and translators have the prominent roles in the development of countries. Many translators really enjoy their work but hesitated to teach a course due to their lack of pedagogical knowledge and believe that the translation skill is gained by personal experiences and talents. Thus this paper attempt to promote the translation teaching in classroom by set the preliminary approach to teach translation. The sequences of teaching design are described by propose the brief definition to the nature of translation the importance translation teaching the translator competence and design of translation course. This paper is the preliminary approach to translation teaching for beginners in university setting.
Inhibition of mTORC1 Enhances the Translation of Chikungunya Proteins via the Activation of the MnK/eIF4E Pathway

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Joubert, Pierre-Emmanuel; Stapleford, Kenneth; Guivel-Benhassine, Florence; Vignuzzi, Marco; Schwartz, Olivier; Albert, Matthew L.

2015-01-01

Chikungunya virus (CHIKV), the causative agent of a major epidemic spanning five continents, is a positive stranded mRNA virus that replicates using the cell’s cap-dependent translation machinery. Despite viral infection inhibiting mTOR, a metabolic sensor controls cap-dependent translation, viral proteins are efficiently translated. Rapalog treatment, silencing of mtor or raptor genes, but not rictor, further enhanced CHIKV infection in culture cells. Using biochemical assays and real time imaging, we demonstrate that this effect is independent of autophagy or type I interferon production. Providing in vivo evidence for the relevance of our findings, mice treated with mTORC1 inhibitors exhibited increased lethality and showed a higher sensitivity to CHIKV. A systematic evaluation of the viral life cycle indicated that inhibition of mTORC1 has a specific positive effect on viral proteins, enhancing viral replication by increasing the translation of both structural and nonstructural proteins. Molecular analysis defined a role for phosphatidylinositol-3 kinase (PI3K) and MAP kinase-activated protein kinase (MnKs) activation, leading to the hyper-phosphorylation of eIF4E. Finally, we demonstrated that in the context of CHIKV inhibition of mTORC1, viral replication is prioritized over host translation via a similar mechanism. Our study reveals an unexpected bypass pathway by which CHIKV protein translation overcomes viral induced mTORC1 inhibition. PMID:26317997
Inhibition of mTORC1 Enhances the Translation of Chikungunya Proteins via the Activation of the MnK/eIF4E Pathway.

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Pierre-Emmanuel Joubert

2015-08-01

Full Text Available Chikungunya virus (CHIKV, the causative agent of a major epidemic spanning five continents, is a positive stranded mRNA virus that replicates using the cell's cap-dependent translation machinery. Despite viral infection inhibiting mTOR, a metabolic sensor controls cap-dependent translation, viral proteins are efficiently translated. Rapalog treatment, silencing of mtor or raptor genes, but not rictor, further enhanced CHIKV infection in culture cells. Using biochemical assays and real time imaging, we demonstrate that this effect is independent of autophagy or type I interferon production. Providing in vivo evidence for the relevance of our findings, mice treated with mTORC1 inhibitors exhibited increased lethality and showed a higher sensitivity to CHIKV. A systematic evaluation of the viral life cycle indicated that inhibition of mTORC1 has a specific positive effect on viral proteins, enhancing viral replication by increasing the translation of both structural and nonstructural proteins. Molecular analysis defined a role for phosphatidylinositol-3 kinase (PI3K and MAP kinase-activated protein kinase (MnKs activation, leading to the hyper-phosphorylation of eIF4E. Finally, we demonstrated that in the context of CHIKV inhibition of mTORC1, viral replication is prioritized over host translation via a similar mechanism. Our study reveals an unexpected bypass pathway by which CHIKV protein translation overcomes viral induced mTORC1 inhibition.
Role of CAP350 in centriolar tubule stability and centriole assembly.

Directory of Open Access Journals (Sweden)

Mikael Le Clech

Full Text Available BACKGROUND: Centrioles are microtubule-based cylindrical structures composed of nine triplet tubules and are required for the formation of the centrosome, flagella and cilia. Despite theirs importance, centriole biogenesis is poorly understood. Centrosome duplication is initiated at the G1/S transition by the sequential recruitment of a set of conserved proteins under the control of the kinase Plk4. Subsequently, the procentriole is assembled by the polymerization of centriolar tubules via an unknown mechanism involving several tubulin paralogs. METHODOLOGY/PRINCIPAL FINDINGS: Here, we developed a cellular assay to study centrosome duplication and procentriole stability based on its sensitivity to the microtubule-depolymerizing drug nocodazole. By using RNA interference experiments, we show that the stability of growing procentrioles is regulated by the microtubule-stabilizing protein CAP350, independently of hSAS-6 and CPAP which initiate procentriole growth. Furthermore, our analysis reveals the critical role of centriolar tubule stability for an efficient procentriole growth. CONCLUSIONS/SIGNIFICANCE: CAP350 belongs to a new class of proteins which associate and stabilize centriolar tubules to control centriole duplication.
Characterization of cap binding proteins associated with the nucleus

International Nuclear Information System (INIS)

Patzelt, E.

1986-04-01

Eucaryotic mRNAs a carry 7-methylguanosine triphosphate residue (called cap structure) at their 5' terminus. The cap plays an important role in RNA recognition. Cap binding proteins (CBP) of HeLa cells were identified by photoaffinity labelling using the cap analogue γ-( 32 P)-(4-(benzoyl-phenyl)methylamido)-7-methylguanosine-5'-triphosphate (BP-m 7 GTP). Photoreaction of this cap analogue with HeLa cell initiation factors resulted in specific labelling of two polypeptides of Msub(r) 37000 and 26000. The latter was also labelled in crude initiation factors prepared from reticulocytes and is identical to the cap binding protein CBP I previously identified. These cap binding proteins were also affinity labelled in poliovirus infected cell extracts. Photoaffinity reaction with BP-m 7 GTP of whole HeLa cell homogenate showed three additional polypeptides with Msub(r) 120000, 89000 and 80000. These cap binding proteins were found to be associated with the nucleus and are therefore referred to as nuclear cap binding proteins, i.e. NCBP 1, NCBP 2 and NCBP 3. They were also present in splicing extracts. Photoaffinity labelling in these nuclear extracts was differentially inhibited by various cap analogues and capped mRNAs. Affinity chromatography on immobilized globin mRNA led to a partial separation of the three nuclear cap binding proteins. Chromatography on m 7 GTP-Sepharose resulted in a specific binding of NCBP 3. The different behaviour of the cap binding proteins suggests that they are functionally distinct and that they might be involved in different processes requiring cap recognition. (Author)
Inhibition of tumor cell growth by Sigma1 ligand mediated translational repression

International Nuclear Information System (INIS)

Kim, Felix J.; Schrock, Joel M.; Spino, Christina M.; Marino, Jacqueline C.; Pasternak, Gavril W.

2012-01-01

Highlights: ► Sigma1 ligand treatment mediates decrease in tumor cell mass. ► Identification of a Sigma1 ligand with reversible translational repressor actions. ► Demonstration of a role for Sigma1 in cellular protein synthesis. -- Abstract: Treatment with sigma1 receptor (Sigma1) ligands can inhibit cell proliferation in vitro and tumor growth in vivo. However, the cellular pathways engaged in response to Sigma1 ligand treatment that contribute to these outcomes remain largely undefined. Here, we show that treatment with putative antagonists of Sigma1 decreases cell mass. This effect corresponds with repressed cap-dependent translation initiation in multiple breast and prostate cancer cell lines. Sigma1 antagonist treatment suppresses phosphorylation of translational regulator proteins p70S6K, S6, and 4E-BP1. RNAi-mediated knockdown of Sigma1 also results in translational repression, consistent with the effects of antagonist treatment. Sigma1 antagonist mediated translational repression and decreased cell size are both reversible. Together, these data reveal a role for Sigma1 in tumor cell protein synthesis, and demonstrate that small molecule Sigma1 ligands can be used as modulators of protein translation.
Neural Network Prediction of Translation Initiation Sites in Eukaryotes: Perspectives for EST and Genome analysis

DEFF Research Database (Denmark)

Pedersen, Anders Gorm; Nielsen, Henrik

1997-01-01

Translation in eukaryotes does not always start at the first AUG in an mRNA, implying that context information also plays a role.This makes prediction of translation initiation sites a non-trivial task, especially when analysing EST and genome data where the entire mature mRNA sequence is not known...
Translation and Psychometric Properties of Persian Version of Independent Living Scale in Patients with Schizophrenia

Directory of Open Access Journals (Sweden)

Khalafbeigi

2016-12-01

Full Text Available Background Independent living skills are major targets for rehabilitation in patients with schizophrenia. So, assessment of their performance is required to obtain valuable information for planning intervention. The independent living scale (ILS is a useful assessment tool for this population. Objectives The aims of this study were to translate the three of five subscales of ILS (“memory/orientation”, “health and safety” and “social adjustment” into Persian language and evaluate their validity. The remaining two subscales of ILS (“money management”, “home management and transportation” have already been translated to Persian language by other researchers in Iran. In addition, the reliability of whole Persian version of ILS subscales was evaluated to be used for patients with Schizophrenia. Methods The three subscales of ILS were translated from English into Persian according to the international quality of life assessment (IQOLA approach. The translation of the three subscales: memory/orientation, health and safety and social adjustment, were analyzed by experts to develop the final version of each subscale. After translation, face and content validity of scale were performed. In face validity evaluation, the scale was investigated by 6 occupational therapists in terms of simplicity, mastery, relationship and clarity or transparency for each of the items. To assess the validity of content, scale was examined by 15 occupational therapists and content validity ratio (CVR and content validity index (CVI of each item were calculated. To assess the reliability of the subscales, test-retest reliability techniques (intraclass correlation coefficient (ICC and standard error of measure (SEM were utilized. Results The simplicity, relevance, clarity and necessity of the translated items were acceptable, according to the CVI and CVR scores. Face validity was also acceptable with respect to agreement rate (> 80%. Test-retest reliability

Heat shock protein 70 promotes coxsackievirus B3 translation initiation and elongation via Akt-mTORC1 pathway depending on activation of p70S6K and Cdc2.

Science.gov (United States)

Wang, Fengping; Qiu, Ye; Zhang, Huifang M; Hanson, Paul; Ye, Xin; Zhao, Guangze; Xie, Ronald; Tong, Lei; Yang, Decheng

2017-07-01

We previously demonstrated that coxsackievirus B3 (CVB3) infection upregulated heat shock protein 70 (Hsp70) and promoted CVB3 multiplication. Here, we report the underlying mechanism by which Hsp70 enhances viral RNA translation. By using an Hsp70-overexpressing cell line infected with CVB3, we found that Hsp70 enhanced CVB3 VP1 translation at two stages. First, Hsp70 induced upregulation of VP1 translation at the initiation stage via upregulation of internal ribosome entry site trans-acting factor lupus autoantigen protein and activation of eIF4E binding protein 1, a cap-dependent translation suppressor. Second, we found that Hsp70 increased CVB3 VP1 translation by enhancing translation elongation. This was mediated by the Akt-mammalian target of rapamycin complex 1 signal cascade, which led to the activation of eukaryotic elongation factor 2 via p70S6K- and cell division cycle protein 2 homolog (Cdc2)-mediated phosphorylation and inactivation of eukaryotic elongation factor 2 kinase. We also determined the position of Cdc2 in this signal pathway, indicating that Cdc2 is regulated by mammalian target of rapamycin complex 1. This signal transduction pathway was validated using a number of specific pharmacological inhibitors, short interfering RNAs (siRNAs) and a dominant negative Akt plasmid. Because Hsp70 is a central component of the cellular network of molecular chaperones enhancing viral replication, these data may provide new strategies to limit this viral infection. © 2017 John Wiley & Sons Ltd.
Stimulation of translation by human Unr requires cold shock domains 2 and 4, and correlates with poly(A) binding protein interaction.

Science.gov (United States)

Ray, Swagat; Anderson, Emma C

2016-03-03

The RNA binding protein Unr, which contains five cold shock domains, has several specific roles in post-transcriptional control of gene expression. It can act as an activator or inhibitor of translation initiation, promote mRNA turnover, or stabilise mRNA. Its role depends on the mRNA and other proteins to which it binds, which includes cytoplasmic poly(A) binding protein 1 (PABP1). Since PABP1 binds to all polyadenylated mRNAs, and is involved in translation initiation by interaction with eukaryotic translation initiation factor 4G (eIF4G), we investigated whether Unr has a general role in translational control. We found that Unr strongly stimulates translation in vitro, and mutation of cold shock domains 2 or 4 inhibited its translation activity. The ability of Unr and its mutants to stimulate translation correlated with its ability to bind RNA, and to interact with PABP1. We found that Unr stimulated the binding of PABP1 to mRNA, and that Unr was required for the stable interaction of PABP1 and eIF4G in cells. siRNA-mediated knockdown of Unr reduced the overall level of cellular translation in cells, as well as that of cap-dependent and IRES-dependent reporters. These data describe a novel role for Unr in regulating cellular gene expression.
Radioimmunological determination of. cap alpha. -MSH and ACTH in the rat

Energy Technology Data Exchange (ETDEWEB)

Usategui Echeverria, R; Oliver, C; Vaudry, H; Lombardi, G; Rozenberg, I; Vague, J [Centre Hospitalier Universitaire de la Timone, 13 - Marseille (France)

1975-09-01

Specific and sensitive radioimmunoassay methods for ..cap alpha..-MSH and ACTH are reported. They make possible specific measurements of each hormone in rat plasma or pituitary extracts. Endogenous ..cap alpha..-MSH and ACTH extracted from plasma or pituitary show the same immunoreactivity than synthetic ..cap alpha..-MSH and ACTH. ..cap alpha..-MSH and ACTH levels vary independently from each other in the following conditions: circadian rythm, corticoid treatment, adrenalectomy, ether stress, haloperidol injection.
Dragon TIS Spotter: An Arabidopsis-derived predictor of translation initiation sites in plants

KAUST Repository

Magana-Mora, Arturo; Ashoor, Haitham; Jankovic, Boris R.; Kamau, Allan; Awara, Karim; Chowdhary, Rajesh; Archer, John A.C.; Bajic, Vladimir B.

2012-01-01

In higher eukaryotes, the identification of translation initiation sites (TISs) has been focused on finding these signals in cDNA or mRNA sequences. Using Arabidopsis thaliana (A.t.) information, we developed a prediction tool for signals within genomic sequences of plants that correspond to TISs. Our tool requires only genome sequence, not expressed sequences. Its sensitivity/specificity is for A.t. (90.75%/92.2%), for Vitis vinifera (66.8%/94.4%) and for Populus trichocarpa (81.6%/94.4%), which suggests that our tool can be used in annotation of different plant genomes. We provide a list of features used in our model. Further study of these features may improve our understanding of mechanisms of the translation initiation. The Author(s) 2012. Published by Oxford University Press.
Dragon TIS Spotter: An Arabidopsis-derived predictor of translation initiation sites in plants

KAUST Repository

Magana-Mora, Arturo

2012-10-30

In higher eukaryotes, the identification of translation initiation sites (TISs) has been focused on finding these signals in cDNA or mRNA sequences. Using Arabidopsis thaliana (A.t.) information, we developed a prediction tool for signals within genomic sequences of plants that correspond to TISs. Our tool requires only genome sequence, not expressed sequences. Its sensitivity/specificity is for A.t. (90.75%/92.2%), for Vitis vinifera (66.8%/94.4%) and for Populus trichocarpa (81.6%/94.4%), which suggests that our tool can be used in annotation of different plant genomes. We provide a list of features used in our model. Further study of these features may improve our understanding of mechanisms of the translation initiation. The Author(s) 2012. Published by Oxford University Press.
The antidepressant sertraline inhibits translation initiation by curtailing mammalian target of rapamycin signaling.

Science.gov (United States)

Lin, Chen-Ju; Robert, Francis; Sukarieh, Rami; Michnick, Stephen; Pelletier, Jerry

2010-04-15

Sertraline, a selective serotonin reuptake inhibitor, is a widely used antidepressant agent. Here, we show that sertraline also exhibits antiproliferative activity. Exposure to sertraline leads to a concentration-dependent decrease in protein synthesis. Moreover, polysome profile analysis of sertraline-treated cells shows a reduction in polysome content and a concomitant increase in 80S ribosomes. The inhibition in translation caused by sertraline is associated with decreased levels of the eukaryotic initiation factor (eIF) 4F complex, altered localization of eIF4E, and increased eIF2alpha phosphorylation. The latter event leads to increased REDD1 expression, which in turn impinges on the mammalian target of rapamycin (mTOR) pathway by affecting TSC1/2 signaling. Sertraline also independently targets the mTOR signaling pathway downstream of Rheb. In the Emu-myc murine lymphoma model where carcinogenesis is driven by phosphatase and tensin homologue (PTEN) inactivation, sertraline is able to enhance chemosensitivity to doxorubicin. Our results indicate that sertraline exerts antiproliferative activity by targeting the mTOR signaling pathway in a REDD1-dependent manner. (c) 2010 AACR.
TECHNOLOGIES OF INITIATING STUDENTS INTO INDEPENDENT (SELF-GUIDED ACTIVITY IN SUPPLEMENTARY DISTANCE LEARNING

Directory of Open Access Journals (Sweden)

Irina V. Abakumova

2016-12-01

Full Text Available The research in question investigates the technologies of initiating independent activity within the framework of distance learning and their psychological aspects. The authors’ classification of educational technologies of initiating students into independent cognitive activity is presented. Such technologies utilize various psychological mechanisms of exciting students’ cognitive interest, intensifying cognitive processes, developing independent activity skills, and, as a result, increase motivation for independent activity and learning on the whole. These include such types of technologies as developmental technologies, interactive technologies, technologies of information transfer, technologies of meaning-making initiation. The research of the attitude of distance learning educators to independent activity of students and the content of the academic courses were done at Moodle-based education programs. The findings show the differences in retention rate among distance learning educators whose competence in terms of initiating students into independent (self-guided activity varies. It’s emphasized that interactive lectures, videoconferences, audio-visual aids, interactive seminars, glossaries, interactive tests are considered the most efficient technologies in initiating students into independent (self-guided activity. The obtained results have made it possible to stress the developmental effect of distance learning technologies and the technologies of initiating students into independent (self-guided activity in various psychic spheres of students: cognitive, individual, emotional. We mention the changes in motivational sphere of students and their meaning-making activity. In the course of correct development of distance learning we notice the development of voluntary and nonvoluntary cognitive activity. A student starts actively participating in educational process, he becomes the creator of his own world.
Design and performance of capping layers for extreme-ultraviolet multilayer mirrors

International Nuclear Information System (INIS)

Bajt, Sasa; Chapman, Henry N.; Nguyen, Nhan; Alameda, Jennifer; Robinson, Jeffrey C.; Malinowski, Michael; Gullikson, Eric; Aquila, Andrew; Tarrio, Charles; Grantham, Steven

2003-01-01

Multilayer lifetime has emerged as one of the major issues for the commercialization of extreme-ultraviolet lithography (EUVL). We describe the performance of an oxidation-resistant capping layer of Ru atop multilayers that results in a reflectivity above 69% at 13.2 nm, which is suitable for EUVL projection optics and has been tested with accelerated electron-beam and extreme-ultraviolet (EUV) light in a water-vapor environment. Based on accelerated exposure results, we calculated multilayer lifetimes for all reflective mirrors in a typical commercial EUVL tool and concluded that Ru-capped multilayers have ∼40x longer lifetimes than Si-capped multilayers, which translates to 3 months to many years, depending on the mirror dose
T-Cap Pull-Off and Bending Behavior for Stitched Structure

Science.gov (United States)

Lovejoy, Andrew E.; Leone, Frank A., Jr.

2016-01-01

The Pultruded Rod Stitched Efficient Unitized Structure (PRSEUS) is a structural concept that was developed by The Boeing Company to address the complex structural design aspects associated with a pressurized hybrid wing body aircraft configuration. An important design feature required for assembly is the integrally stitched T-cap, which provides connectivity of the corner (orthogonal) joint between adjacent panels. A series of tests were conducted on T-cap test articles, with and without a rod stiffener penetrating the T-cap web, under tension (pull-off) and bending loads. Three designs were tested, including the baseline design used in largescale test articles. The baseline had only the manufacturing stitch row adjacent to the fillet at the base of the T-cap web. Two new designs added stitching rows to the T-cap web at either 0.5- or 1.0-inch spacing along the height of the web. Testing was conducted at NASA Langley Research Center to determine the behavior of the T-cap region resulting from the applied loading. Results show that stitching arrests the initial delamination failures so that the maximum strength capability exceeds the load at which the initial delaminations develop. However, it was seen that the added web stitching had very little effect on the initial delamination failure load, but actually decreased the initial delamination failure load for tension loading of test articles without a stiffener passing through the web. Additionally, the added web stitching only increased the maximum load capability by between 1% and 12.5%. The presence of the stiffener, however, did increase the initial and maximum loads for both tension and bending loading as compared to the stringerless baseline design. Based on the results of the few samples tested, the additional stitching in the T-cap web showed little advantage over the baseline design in terms of structural failure at the T-cap web/skin junction for the current test articles.
From what we know to what we do: lessons learned from the translational CLAHRC initiative in England.

Science.gov (United States)

Currie, Graeme; Lockett, Andy; El Enany, Nellie

2013-10-01

There exists a translation gap between academic research and clinical practice in health care systems. One policy-driven initiative to address the translation gap in England are the Collaborations for Leadership in Applied Health Research and Care (CLAHRCs), funded by the National Institute of Health Research (NIHR). These aim to bring together NHS organizations and universities to accelerate the translation of evidence-based innovation into clinical practice. Our aim was to draw out lessons for policy-makers regarding the mobilization of such initiatives. Qualitative semi-structured interviews with 174 participants across nine CLAHRCs plus in-depth case studies across four CLAHRCs. Those interviewed were staff who were central to the CLAHRCs including senior managers and directors, junior and senior academics, and health care practitioners. Social positions of the CLAHRC leaders, conceived as institutional entrepreneurs, together with the antecedent conditions for CLAHRC bids, had an impact on the vision for a CLAHRC. The process of envisioning encompassed diagnostic and prognostic framing. Within the envisioning process, the utilization of existing activities and established relationships in the CLAHRC bid influenced early mobilization. However, in some cases, it led to a translational 'lock in' towards established models regarding applied research. The CLAHRC experiment in England holds important lessons for policy-makers regarding how to address the translation gap. First, policy makers need to consider whether they set out a defined template for translational initiatives or whether variation is encouraged. We might expect a degree of learning from pilot activities within a CLAHRC that allows for greater clarity in the design of subsequent translational initiatives. Second, policy makers and practitioners need to understand the importance of both antecedent conditions and the social position of senior members of a CLAHRC (institutional entrepreneurs) leading
Independence: proposing an initial framework for occupational therapy.

Science.gov (United States)

Collins, Bethan

2017-11-01

The concept of independence is common in occupational therapy theory and practice but has rarely been clearly defined or conceptualized within in occupational therapy literature and there seems to be no standard definition. This can result in ambiguity, which potentially jeopardizes client-centred practice. This paper proposes an occupational therapy independence framework (OTIF) that synthesizes the range of characterizations of independence in a practically useful and occupation-centred manner. A review of literature, clinical experience, doctoral research and conversations with occupational therapists and disabled people, in particular those involved in a disability activism group and people with physical disabilities, has led to the development of the OTIF. Independence and interdependence, as characterized in the OTIF, occur when an individual exerts choice over occupational performance and can engage in occupations in a manner acceptable to the individual. Interdependence results when occupations are performed with another person whereas independence involves solitary occupational performance. Dependence typically results from inability to choose occupations or a mismatch between performance capacity and environmental factors. The OTIF has the potential to clarify the conceptualization of independence within occupational therapy theory and practice. This initial proposal is presented to stimulate debate and discussion.
Harmonization in preclinical epilepsy research: A joint AES/ILAE translational initiative.

Science.gov (United States)

Galanopoulou, Aristea S; French, Jacqueline A; O'Brien, Terence; Simonato, Michele

2017-11-01

Among the priority next steps outlined during the first translational epilepsy research workshop in London, United Kingdom (2012), jointly organized by the American Epilepsy Society (AES) and the International League Against Epilepsy (ILAE), are the harmonization of research practices used in preclinical studies and the development of infrastructure that facilitates multicenter preclinical studies. The AES/ILAE Translational Task Force of the ILAE has been pursuing initiatives that advance these goals. In this supplement, we present the first reports of the working groups of the Task Force that aim to improve practices of performing rodent video-electroencephalography (vEEG) studies in experimental controls, generate systematic reviews of preclinical research data, and develop preclinical common data elements (CDEs) for epilepsy research in animals. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.
Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms

OpenAIRE

Kahvejian, Avak; Svitkin, Yuri V.; Sukarieh, Rami; M'Boutchou, Marie-Noël; Sonenberg, Nahum

2005-01-01

Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5′-end of the mRNA to promote the recruitment of the ribosome. Although the 3′ poly(A) tail of eukaryotic mRNAs and its major bound protein, the poly(A)-binding protein (PABP), have been studied extensively, their mechanism of action in translation is not well understood and is confounded by differences between in vivo and in vitro systems. Here, we provide direct evidence for ...
No Escaping the Rat Race: Simulated Night Shift Work Alters the Time-of-Day Variation in BMAL1 Translational Activity in the Prefrontal Cortex.

Science.gov (United States)

Marti, Andrea R; Patil, Sudarshan; Mrdalj, Jelena; Meerlo, Peter; Skrede, Silje; Pallesen, Ståle; Pedersen, Torhild T; Bramham, Clive R; Grønli, Janne

2017-01-01

Millions of people worldwide work during the night, resulting in disturbed circadian rhythms and sleep loss. This may cause deficits in cognitive functions, impaired alertness and increased risk of errors and accidents. Disturbed circadian rhythmicity resulting from night shift work could impair brain function and cognition through disrupted synthesis of proteins involved in synaptic plasticity and neuronal function. Recently, the circadian transcription factor brain-and-muscle arnt-like protein 1 (BMAL1) has been identified as a promoter of mRNA translation initiation, the most highly regulated step in protein synthesis, through binding to the mRNA "cap". In this study we investigated the effects of simulated shift work on protein synthesis markers. Male rats ( n = 40) were exposed to forced activity, either in their rest phase (simulated night shift work) or in their active phase (simulated day shift work) for 3 days. Following the third work shift, experimental animals and time-matched undisturbed controls were euthanized (rest work at ZT12; active work at ZT0). Tissue lysates from two brain regions (prefrontal cortex, PFC and hippocampus) implicated in cognition and sleep loss, were analyzed with m 7 GTP (cap) pull-down to examine time-of-day variation and effects of simulated shift work on cap-bound protein translation. The results show time-of-day variation of protein synthesis markers in PFC, with increased protein synthesis at ZT12. In the hippocampus there was little difference between ZT0 and ZT12. Active phase work did not induce statistically significant changes in protein synthesis markers at ZT0 compared to time-matched undisturbed controls. Rest work, however, resulted in distinct brain-region specific changes of protein synthesis markers compared to time-matched controls at ZT12. While no changes were observed in the hippocampus, phosphorylation of cap-bound BMAL1 and its regulator S6 kinase beta-1 (S6K1) was significantly reduced in the PFC
Translation of dipeptide repeat proteins from the C9ORF72 expanded repeat is associated with cellular stress.

Science.gov (United States)

Sonobe, Yoshifumi; Ghadge, Ghanashyam; Masaki, Katsuhisa; Sendoel, Ataman; Fuchs, Elaine; Roos, Raymond P

2018-08-01

Expansion of a hexanucleotide repeat (HRE), GGGGCC, in the C9ORF72 gene is recognized as the most common cause of familial amyotrophic lateral sclerosis (FALS), frontotemporal dementia (FTD) and ALS-FTD, as well as 5-10% of sporadic ALS. Despite the location of the HRE in the non-coding region (with respect to the main C9ORF72 gene product), dipeptide repeat proteins (DPRs) that are thought to be toxic are translated from the HRE in all three reading frames from both the sense and antisense transcript. Here, we identified a CUG that has a good Kozak consensus sequence as the translation initiation codon. Mutation of this CTG significantly suppressed polyglycine-alanine (GA) translation. GA was translated when the G 4 C 2 construct was placed as the second cistron in a bicistronic construct. CRISPR/Cas9-induced knockout of a non-canonical translation initiation factor, eIF2A, impaired GA translation. Transfection of G 4 C 2 constructs induced an integrated stress response (ISR), while triggering the ISR led to a continuation of translation of GA with a decline in conventional cap-dependent translation. These in vitro observations were confirmed in chick embryo neural cells. The findings suggest that DPRs translated from an HRE in C9ORF72 aggregate and lead to an ISR that then leads to continuing DPR production and aggregation, thereby creating a continuing pathogenic cycle. Copyright © 2018 Elsevier Inc. All rights reserved.
Two-Stage Translational Control of Dentate Gyrus LTP Consolidation Is Mediated by Sustained BDNF-TrkB Signaling to MNK

Directory of Open Access Journals (Sweden)

Debabrata Panja

2014-11-01

Full Text Available BDNF signaling contributes to protein-synthesis-dependent synaptic plasticity, but the dynamics of TrkB signaling and mechanisms of translation have not been defined. Here, we show that long-term potentiation (LTP consolidation in the dentate gyrus of live rodents requires sustained (hours BDNF-TrkB signaling. Surprisingly, this sustained activation maintains an otherwise labile signaling pathway from TrkB to MAP-kinase-interacting kinase (MNK. MNK activity promotes eIF4F translation initiation complex formation and protein synthesis in mechanistically distinct early and late stages. In early-stage translation, MNK triggers release of the CYFIP1/FMRP repressor complex from the 5′-mRNA cap. In late-stage translation, MNK regulates the canonical translational repressor 4E-BP2 in a synapse-compartment-specific manner. This late stage is coupled to MNK-dependent enhanced dendritic mRNA translation. We conclude that LTP consolidation in the dentate gyrus is mediated by sustained BDNF signaling to MNK and MNK-dependent regulation of translation in two functionally and mechanistically distinct stages.
Dragon TIS Spotter: an Arabidopsis-derived predictor of translation initiation sites in plants.

Science.gov (United States)

Magana-Mora, Arturo; Ashoor, Haitham; Jankovic, Boris R; Kamau, Allan; Awara, Karim; Chowdhary, Rajesh; Archer, John A C; Bajic, Vladimir B

2013-01-01

In higher eukaryotes, the identification of translation initiation sites (TISs) has been focused on finding these signals in cDNA or mRNA sequences. Using Arabidopsis thaliana (A.t.) information, we developed a prediction tool for signals within genomic sequences of plants that correspond to TISs. Our tool requires only genome sequence, not expressed sequences. Its sensitivity/specificity is for A.t. (90.75%/92.2%), for Vitis vinifera (66.8%/94.4%) and for Populus trichocarpa (81.6%/94.4%), which suggests that our tool can be used in annotation of different plant genomes. We provide a list of features used in our model. Further study of these features may improve our understanding of mechanisms of the translation initiation. Our tool is implemented as an artificial neural network. It is available as a web-based tool and, together with the source code, the list of features, and data used for model development, is accessible at http://cbrc.kaust.edu.sa/dts.
A guide to the translation of the Global Initiative for Asthma (GINA) strategy into improved care

DEFF Research Database (Denmark)

Boulet, Louis-Philippe; FitzGerald, J Mark; Levy, Mark L

2012-01-01

In 1995, the Global Initiative for Asthma (GINA) published an evidence-based workshop report as a guide to clinicians managing asthma patients, and has updated it annually to ensure that recommendations remain current. Although the report has been widely disseminated and influenced clinical...... practice and research, its major objective, of forming the basis for local and national initiatives to improve services for asthma patients, remains to be achieved. Over recent years, the science of guideline implementation has progressed, and encouraging examples of successful asthma programmes have been...... published. This report is intended to draw on this experience and assist with the translation of asthma guideline recommendations into quality programmes for patients with asthma using current knowledge translation principles. It also provides examples of successful initiatives in various socioeconomic...
ER stress inducer tunicamycin suppresses the self-renewal of glioma-initiating cell partly through inhibiting Sox2 translation.

Science.gov (United States)

Xing, Yang; Ge, Yuqing; Liu, Chanjuan; Zhang, Xiaobiao; Jiang, Jianhai; Wei, Yuanyan

2016-06-14

Glioma-initiating cells possess tumor-initiating potential and are relatively resistant to conventional chemotherapy and irradiation. Therefore, their elimination is an essential factor for the development of efficient therapy. Here, we report that endoplasmic reticulum (ER) stress inducer tunicamycin inhibits glioma-initiating cell self-renewal as determined by neurosphere formation assay. Moreover, tunicamycin decreases the efficiency of glioma-initiating cell to initiate tumor formation. Although tunicamycin induces glioma-initiating cell apoptosis, apoptosis inhibitor z-VAD-fmk only partly abrogates the reduction in glioma-initiating cell self-renewal induced by tunicamycin. Indeed, tunicamycin reduces the expression of self-renewal regulator Sox2 at translation level. Overexpression of Sox2 obviously abrogates the reduction in glioma-initiating cell self-renewal induced by tunicamycin. Taken together, tunicamycin suppresses the self-renewal and tumorigenic potential of glioma-initiating cell partly through reducing Sox2 translation. This finding provides a cue to potential effective treatment of glioblastoma through controlling stem cells.
Beyond initiation-limited translational bursting: the effects of burst size distributions on the stability of gene expression

KAUST Repository

Kuwahara, Hiroyuki

2015-11-04

A main source of gene expression noise in prokaryotes is translational bursting. It arises from efficient translation of mRNAs with low copy numbers, which makes the production of protein copies highly variable and pulsatile. To obtain analytical solutions, previous models to capture this noise source had to assume translation to be initiation-limited, representing the burst size by a specific type of a long-tail distribution. However, there is increasing evidence suggesting that the initiation is not the rate-limiting step in certain settings, for example, under stress conditions. Here, to overcome the limitations imposed by the initiation-limited assumption, we present a new analytical approach that can evaluate biological consequences of the protein burst size with a general distribution. Since our new model can capture the contribution of other factors to the translational noise, it can be used to analyze the effects of gene expression noise in more general settings. We used this new model to analytically analyze the connection between the burst size and the stability of gene expression processes in various settings. We found that the burst size with different distributions can lead to quantitatively and qualitatively different stability characteristics of protein abundance and can have non-intuitive effects. By allowing analysis of how the stability of gene expression processes changes based on various distributions of translational noise, our analytical approach is expected to enable deeper insights into the control of cell fate decision-making, the evolution of cryptic genetic variations, and fine-tuning of gene circuits.

Beyond initiation-limited translational bursting: the effects of burst size distributions on the stability of gene expression

KAUST Repository

Kuwahara, Hiroyuki; Arold, Stefan T.; Gao, Xin

2015-01-01

solutions, previous models to capture this noise source had to assume translation to be initiation-limited, representing the burst size by a specific type of a long-tail distribution. However, there is increasing evidence suggesting that the initiation
Translation of satellite tobacco necrosis virus RNA modified by (not equal to)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene is inhibited in a wheat germ cell-free system

International Nuclear Information System (INIS)

Haas, R.; Pulkrabek, P.; Takanami, Y.; Grunberger, D.

1983-01-01

It has been shown that (not equal to)-r-7-,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) modification of rabbit globin mRNA results in inhibition of translational initiation. In order to explore the possibility that modification of the 5' cap structure was responsible for this inhibition, the naturally non-capped mRNA from satellite tobacco necrosis virus (STNV) was reacted with BPDE and translated in a wheat germ cell-free system. The extent of modification was 1.3 and 2.9 BPDE residues/molecule. High performance liquid chromatography of the modified nucleosides from enzymatically hydrolyzed STNV RNA revealed that greater than 90% of the nucleoside adducts were substituted at the exocyclic amino group of guanosine. The translational ability of the lower and higher modified STNV, measured by incorporation of [ 14 C]amino acids into acid-precipitable polypeptides is inhibited by 55% and 63%, respectively. Polyacrylamide gel electrophoretic analyses of the translation products indicate that predominantly full-length coat proteins are synthesized but with the carcinogen-modified STNV the amount is reduced. On the other hand, 80S initiation complex formation is not inhibited as measured by binding of the BPDE-modified STNV to ribosomes and followed by glycerol gradient centrifugation. Under these conditions, aurintricarboxylic acid completely inhibits 80S initiation complex formation in the presence of either modified or native STNV. These results suggest that inhibition of in vitro translation of BPDE-modified STNV, in contrast to that of globin mRNA, is not at the level of initiation complex formation but possibly by premature termination of growing polypeptides
Increased 5. cap alpha. -reductase activity in idiopathic hirsutism

Energy Technology Data Exchange (ETDEWEB)

Serafini, P.; Lobo, R.A.

1985-01-01

In vitro, genital skin 5..cap alpha..-reductase activity (5..cap alpha..-RA) was measured in ten hirsute women with normal androgen levels (idiopathic hirsutism (IH)) and in ten hirsute women with elevated androgen levels (polycystic ovary syndrome (PCO)) in order to determine the influence of secreted androgens on 5..cap alpha..-RA. In vitro 5..cap alpha..-RA was assessed by incubations of skin with /sup 14/C-testosterone (T) for 2 hours, after which steroids were separated and the radioactivity of dihydrotestosterone (DHT) and 5..cap alpha..-androstane 3..cap alpha..-17..beta..-estradiol (3..cap alpha..-diol) in specific eluates were determined. All androgens were normal in IH with the exception of higher levels of 3..cap alpha..-diol glucuronide which were similar to the levels of PCO. The conversion ratio (CR) of T to DHT in IH and PCO were similar, yet significantly greater than the CR of control subjects. The CR of T to 3..cap alpha..-diol in IH and PCO were similar, yet higher than in control subjects. Serum androgens showed no correlation with 5..cap alpha..-RA, while the CR of T to DHT showed a significant positive correlation with the Ferriman and Gallwey score. The increased 5..cap alpha..-RA in IH appears to be independent of serum androgen levels and is, therefore, an inherent abnormality. The term idiopathic is a misnomer, because hirsutism in these patients may be explained on the basis of increased skin 5..cap alpha..-RA.
Characterization of the functional role of nucleotides within the URE2 IRES element and the requirements for eIF2A-mediated repression.

Science.gov (United States)

Reineke, Lucas C; Merrick, William C

2009-12-01

Cap-independent initiation of translation is thought to promote protein synthesis on some mRNAs during times when cap-dependent initiation is down-regulated. However, the mechanism of cap-independent initiation is poorly understood. We have previously reported the secondary structure within the yeast minimal URE2 IRES element. In this study, we sought to investigate the mechanism of internal initiation in yeast by assessing the functional role of nucleotides within the minimal URE2 IRES element, and delineating the cis-sequences that modulate levels of internal initiation using a monocistronic reporter vector. Furthermore, we compared the eIF2A sensitivity of the URE2 IRES element with some of the invasive growth IRES elements using DeltaeIF2A yeast. We found that the stability of the stem-loop structure within the minimal URE2 IRES element is not a critical determinant of optimal IRES activity, and the downstream sequences that modulate URE2 IRES-mediated translation can be defined to discrete regions within the URE2 coding region. Repression of internal initiation on the URE2 minimal IRES element by eIF2A is not dependent on the stability of the secondary structure within the URE2 IRES element. Our data also indicate that eIF2A-mediated repression is not specific to the URE2 IRES element, as both the GIC1 and PAB1 IRES elements are repressed by eIF2A. These data provide valuable insights into the mRNA requirements for internal initiation in yeast, and insights into the mechanism of eIF2A-mediated suppression.
Monocistronic mRNAs containing defective hepatitis C virus-like picornavirus internal ribosome entry site elements in their 5 ' untranslated regions are efficiently translated in cells by a cap-dependent mechanism

DEFF Research Database (Denmark)

Belsham, Graham; Nielsen, Inge; Normann, Preben

2008-01-01

The initiation of protein synthesis on mRNAs within eukaryotic cells is achieved either by a 5' cap-dependent mechanism or through internal initiation directed by an internal ribosome entry site (IRES). Picornavirus IRES elements, located in the 59 untranslated region (5'UTR), contain extensive s...
Integration of the End Cap TEC+ of the CMS Silicon Strip Tracker

CERN Document Server

Adler, Volker; Ageron, Michel; Agram, Jean-Laurent; Atz, Bernd; Barvich, Tobias; Baulieu, Guillaume; Beaumont, Willem; Beissel, Franz; Bergauer, Thomas; Berst, Jean-Daniel; Blüm, Peter; Bock, E; Bogelsbacher, F; de Boer, Wim; Bonnet, Jean-Luc; Bonnevaux, Alain; Boudoul, Gaelle; Bouhali, Othmane; Braunschweig, Wolfgang; Bremer, R; Brom, Jean-Marie; Butz, Erik; Chabanat, Eric; Chabert, Eric Christian; Clerbaux, Barbara; Contardo, Didier; De Callatay, Bernard; Dehm, Philip; Delaere, Christophe; Della Negra, Rodolphe; Dewulf, Jean-Paul; D'Hondt, Jorgen; Didierjean, Francois; Dierlamm, Alexander; Dirkes, Guido; Dragicevic, Marko; Drouhin, Frédéric; Ernenwein, Jean-Pierre; Esser, Hans; Estre, Nicolas; Fahrer, Manuel; Feld, Lutz; Fernández, J; Florins, Benoit; Flossdorf, Alexander; Flucke, Gero; Flügge, Günter; Fontaine, Jean-Charles; Freudenreich, Klaus; Frey, Martin; Friedl, Markus; Furgeri, Alexander; Giraud, Noël; Goerlach, Ulrich; Goorens, Robert; Graehling, Philippe; Grégoire, Ghislain; Gregoriev, E; Gross, Laurent; Hansel, S; Haroutunian, Roger; Hartmann, Frank; Heier, Stefan; Hermanns, Thomas; Heydhausen, Dirk; Heyninck, Jan; Hosselet, J; Hrubec, Josef; Jahn, Dieter; Juillot, Pierre; Kaminski, Jochen; Karpinski, Waclaw; Kaussen, Gordon; Keutgen, Thomas; Klanner, Robert; Klein, Katja; König, Stefan; Kosbow, M; Krammer, Manfred; Ledermann, Bernhard; Lemaître, Vincent; De Lentdecker, Gilles; Linn, Alexander; Lounis, Abdenour; Lübelsmeyer, Klaus; Lumb, Nicholas; Maazouzi, Chaker; Mahmoud, Tariq; Michotte, Daniel; Militaru, Otilia; Mirabito, Laurent; Müller, Thomas; Neukermans, Lionel; Ollivetto, C; Olzem, Jan; Ostapchuk, Andrey; Pandoulas, Demetrios; Pein, Uwe; Pernicka, Manfred; Perriès, Stephane; Piaseki, C; Pierschel, Gerhard; Piotrzkowski, Krzysztof; Poettgens, Michael; Pooth, Oliver; Rouby, Xavier; Sabellek, Andreas; Schael, Stefan; Schirm, Norbert; Schleper, Peter; Schmitz, Stefan Antonius; Schultz von Dratzig, Arndt; Siedling, Rolf; Simonis, Hans-Jürgen; Stahl, Achim; Steck, Pia; Steinbruck, G; Stoye, Markus; Strub, Roger; Tavernier, Stefaan; Teyssier, Daniel; Theel, Andreas; Trocmé, Benjamin; Udo, Fred; Van der Donckt, M; Van der Velde, C; Van Hove, Pierre; Vanlaer, Pascal; Van Lancker, Luc; Van Staa, Rolf; Vanzetto, Sylvain; Weber, Markus; Weiler, Thomas; Weseler, Siegfried; Wickens, John; Wittmer, Bruno; Wlochal, Michael; De Wolf, Eddi A; Zhukov, Valery; Zoeller, Marc Henning

2009-01-01

The silicon strip tracker of the CMS experiment has been completed and inserted into the CMS detector in late 2007. The largest sub-system of the tracker is its end cap system, comprising two large end caps (TEC) each containing 3200 silicon strip modules. To ease construction, the end caps feature a modular design: groups of about 20 silicon modules are placed on sub-assemblies called petals and these self-contained elements are then mounted into the TEC support structures. Each end cap consists of 144 petals, and the insertion of these petals into the end cap structure is referred to as TEC integration. The two end caps were integrated independently in Aachen (TEC+) and at CERN (TEC--). This note deals with the integration of TEC+, describing procedures for end cap integration and for quality control during testing of integrated sections of the end cap and presenting results from the testing.
Cervical Cap

Science.gov (United States)

... Videos for Educators Search English Español The Cervical Cap KidsHealth / For Teens / The Cervical Cap What's in ... Call the Doctor? Print What Is a Cervical Cap? A cervical cap is a small cup made ...
Tuning of Recombinant Protein Expression in Escherichia coli by Manipulating Transcription, Translation Initiation Rates, and Incorporation of Noncanonical Amino Acids.

Science.gov (United States)

Schlesinger, Orr; Chemla, Yonatan; Heltberg, Mathias; Ozer, Eden; Marshall, Ryan; Noireaux, Vincent; Jensen, Mogens Høgh; Alfonta, Lital

2017-06-16

Protein synthesis in cells has been thoroughly investigated and characterized over the past 60 years. However, some fundamental issues remain unresolved, including the reasons for genetic code redundancy and codon bias. In this study, we changed the kinetics of the Eschrichia coli transcription and translation processes by mutating the promoter and ribosome binding domains and by using genetic code expansion. The results expose a counterintuitive phenomenon, whereby an increase in the initiation rates of transcription and translation lead to a decrease in protein expression. This effect can be rescued by introducing slow translating codons into the beginning of the gene, by shortening gene length or by reducing initiation rates. On the basis of the results, we developed a biophysical model, which suggests that the density of co-transcriptional-translation plays a role in bacterial protein synthesis. These findings indicate how cells use codon bias to tune translation speed and protein synthesis.
Knowledge Translation Interventions to Improve the Timing of Dialysis Initiation: Protocol for a Cluster Randomized Trial.

Science.gov (United States)

Chau, Elaine M T; Manns, Braden J; Garg, Amit X; Sood, Manish M; Kim, S Joseph; Naimark, David; Nesrallah, Gihad E; Soroka, Steven D; Beaulieu, Monica; Dixon, Stephanie; Alam, Ahsan; Tangri, Navdeep

2016-01-01

Early initiation of chronic dialysis (starting dialysis with higher vs lower kidney function) has risen rapidly in the past 2 decades in Canada and internationally, despite absence of established health benefits and higher costs. In 2014, a Canadian guideline on the timing of dialysis initiation, recommending an intent-to-defer approach, was published. The objective of this study is to evaluate the efficacy and safety of a knowledge translation intervention to promote the intent-to-defer approach in clinical practice. This study is a multicenter, 2-arm parallel, cluster randomized trial. The study involves 55 advanced chronic kidney disease clinics across Canada. Patients older than 18 years who are managed by nephrologists for more than 3 months, and initiate dialysis in the follow-up period are included in the study. Outcomes will be measured at the patient-level and enumerated within a cluster. Data on characteristics of each dialysis start will be determined by linkages with the Canadian Organ Replacement Register. Primary outcomes include the proportion of patients who start dialysis early with an estimated glomerular filtration rate greater than 10.5 mL/min/1.73 m 2 and start dialysis in hospital as inpatients or in an emergency room setting. Secondary outcomes include the rate of change in early dialysis starts; rates of hospitalizations, deaths, and cost of predialysis care (wherever available); quarterly proportion of new starts; and acceptability of the knowledge translation materials. We randomized 55 multidisciplinary chronic disease clinics (clusters) in Canada to receive either an active knowledge translation intervention or no intervention for the uptake of the guideline on the timing of dialysis initiation. The active knowledge translation intervention consists of audit and feedback as well as patient- and provider-directed educational tools delivered at a comprehensive in-person medical detailing visit. Control clinics are only exposed to guideline
Androgen signaling promotes translation of TMEFF2 in prostate cancer cells via phosphorylation of the α subunit of the translation initiation factor 2.

Directory of Open Access Journals (Sweden)

Ryan F Overcash

Full Text Available The type I transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2, is expressed mainly in brain and prostate. Expression of TMEFF2 is deregulated in prostate cancer, suggesting a role in this disease, but the molecular mechanism(s involved in this effect are not clear. Although androgens promote tmeff2 transcription, androgen delivery to castrated animals carrying CWR22 xenografts increases TMEFF2 protein levels in the absence of mRNA changes, suggesting that TMEFF2 may also be post-transcriptionally regulated. Here we show that translation of TMEFF2 is regulated by androgens. Addition of physiological concentrations of dihydrotestosterone (DHT to prostate cancer cell lines increases translation of endogenous TMEFF2 or transfected TMEFF2-Luciferase fusions, and this effect requires the presence of upstream open reading frames (uORFs in the 5'-untranslated region (5'-UTR of TMEFF2. Using chemical and siRNA inhibition of the androgen receptor (AR, we show that the androgen effect on TMEFF2 translation is mediated by the AR. Importantly, DHT also promotes phosphorylation of the α subunit of the translation initiation factor 2 (eIF2α in an AR-dependent manner, paralleling the effect on TMEFF2 translation. Moreover, endoplasmic reticulum (ER stress conditions, which promote eIF2α phosphorylation, also stimulate TMEFF2 translation. These results indicate that androgen signaling promotes eIF2α phosphorylation and subsequent translation of TMEFF2 via a mechanism that requires uORFs in the 5'-UTR of TMEFF2.
Modifying chemotherapy response by targeted inhibition of eukaryotic initiation factor 4A

International Nuclear Information System (INIS)

Cencic, R; Robert, F; Galicia-Vázquez, G; Malina, A; Ravindar, K; Somaiah, R; Pierre, P; Tanaka, J; Deslongchamps, P; Pelletier, J

2013-01-01

Translation is regulated predominantly at the initiation phase by several signal transduction pathways that are often usurped in human cancers, including the PI3K/Akt/mTOR axis. mTOR exerts unique administration over translation by regulating assembly of eukaryotic initiation factor (eIF) 4F, a heterotrimeric complex responsible for recruiting 40S ribosomes (and associated factors) to mRNA 5′ cap structures. Hence, there is much interest in targeted therapies that block eIF4F activity to assess the consequences on tumor cell growth and chemotherapy response. We report here that hippuristanol (Hipp), a translation initiation inhibitor that selectively inhibits the eIF4F RNA helicase subunit, eIF4A, resensitizes Eμ-Myc lymphomas to DNA damaging agents, including those that overexpress eIF4E—a modifier of rapamycin responsiveness. As Mcl-1 levels are significantly affected by Hipp, combining its use with the Bcl-2 family inhibitor, ABT-737, leads to a potent synergistic response in triggering cell death in mouse and human lymphoma and leukemia cells. Suppression of eIF4AI using RNA interference also synergized with ABT-737 in murine lymphomas, highlighting eIF4AI as a therapeutic target for modulating tumor cell response to chemotherapy
Inflammatory conditions induce IRES-dependent translation of cyp24a1.

Directory of Open Access Journals (Sweden)

Daniela Rübsamen

Full Text Available Rapid alterations in protein expression are commonly regulated by adjusting translation. In addition to cap-dependent translation, which is e.g. induced by pro-proliferative signaling via the mammalian target of rapamycin (mTOR-kinase, alternative modes of translation, such as internal ribosome entry site (IRES-dependent translation, are often enhanced under stress conditions, even if cap-dependent translation is attenuated. Common stress stimuli comprise nutrient deprivation, hypoxia, but also inflammatory signals supplied by infiltrating immune cells. Yet, the impact of inflammatory microenvironments on translation in tumor cells still remains largely elusive. In the present study, we aimed at identifying translationally deregulated targets in tumor cells under inflammatory conditions. Using polysome profiling and microarray analysis, we identified cyp24a1 (1,25-dihydroxyvitamin D3 24-hydroxylase to be translationally upregulated in breast tumor cells co-cultured with conditioned medium of activated monocyte-derived macrophages (CM. Using bicistronic reporter assays, we identified and validated an IRES within the 5' untranslated region (5'UTR of cyp24a1, which enhances translation of cyp24a1 upon CM treatment. Furthermore, IRES-dependent translation of cyp24a1 by CM was sensitive to phosphatidyl-inositol-3-kinase (PI3K inhibition, while constitutive activation of Akt sufficed to induce its IRES activity. Our data provide evidence that cyp24a1 expression is translationally regulated via an IRES element, which is responsive to an inflammatory environment. Considering the negative feedback impact of cyp24a1 on the vitamin D responses, the identification of a novel, translational mechanism of cyp24a1 regulation might open new possibilities to overcome the current limitations of vitamin D as tumor therapeutic option.
No Escaping the Rat Race: Simulated Night Shift Work Alters the Time-of-Day Variation in BMAL1 Translational Activity in the Prefrontal Cortex

Directory of Open Access Journals (Sweden)

Andrea R. Marti

2017-10-01

Full Text Available Millions of people worldwide work during the night, resulting in disturbed circadian rhythms and sleep loss. This may cause deficits in cognitive functions, impaired alertness and increased risk of errors and accidents. Disturbed circadian rhythmicity resulting from night shift work could impair brain function and cognition through disrupted synthesis of proteins involved in synaptic plasticity and neuronal function. Recently, the circadian transcription factor brain-and-muscle arnt-like protein 1 (BMAL1 has been identified as a promoter of mRNA translation initiation, the most highly regulated step in protein synthesis, through binding to the mRNA “cap”. In this study we investigated the effects of simulated shift work on protein synthesis markers. Male rats (n = 40 were exposed to forced activity, either in their rest phase (simulated night shift work or in their active phase (simulated day shift work for 3 days. Following the third work shift, experimental animals and time-matched undisturbed controls were euthanized (rest work at ZT12; active work at ZT0. Tissue lysates from two brain regions (prefrontal cortex, PFC and hippocampus implicated in cognition and sleep loss, were analyzed with m7GTP (cap pull-down to examine time-of-day variation and effects of simulated shift work on cap-bound protein translation. The results show time-of-day variation of protein synthesis markers in PFC, with increased protein synthesis at ZT12. In the hippocampus there was little difference between ZT0 and ZT12. Active phase work did not induce statistically significant changes in protein synthesis markers at ZT0 compared to time-matched undisturbed controls. Rest work, however, resulted in distinct brain-region specific changes of protein synthesis markers compared to time-matched controls at ZT12. While no changes were observed in the hippocampus, phosphorylation of cap-bound BMAL1 and its regulator S6 kinase beta-1 (S6K1 was significantly reduced in
'Inhabiting' the Translator's Habitus – Antjie Krog as Translator ...

African Journals Online (AJOL)

Drawing on the Bourdieusian concept of habitus and its applicability in the field of translation, this article discusses Antjie Krog's profile in the practice of translation in. South Africa. Bourdieu's conceptualisation of the relationship between the initiating activities of translators and the structures which constrain and enable ...
A nucleation theory of cell surface capping

International Nuclear Information System (INIS)

Coutsias, E.A.; Wester, M.J.; Perelson, A.S.

1997-01-01

We propose a new theory of cell surface capping based on the principles of nucleation. When antibody interacts with cell surface molecules, the molecules initially form small aggregates called patches that later coalesce into a large aggregate called a cap. While a cap can form by patches being pulled together by action of the cell''s cytoskeleton, in the case of some molecules, disruption of the cytoskeleton does not prevent cap formation. Diffusion of large aggregates on a cell surface is slow, and thus we propose that a cap can form solely through the diffusion of small aggregates containing just one or a few cell surface molecules. Here we consider the extreme case in which single molecules are mobile, but aggregates of all larger sizes are immobile. We show that a set of patches in equilibrium with a open-quotes seaclose quotes of free cell surface molecules can undergo a nucleation-type phase transition in which the largest patch will bind free cell surface molecules, deplete the concentration of such molecules in the open-quotes seaclose quotes and thus cause the other patches to shrink in size. We therefore show that a cap can form without patches having to move, collide with each other, and aggregate
Crystallization and preliminary X-ray diffraction analysis of the MIF4G domain of DAP5

International Nuclear Information System (INIS)

Frank, Filipp; Virgili, Geneviève; Sonenberg, Nahum; Nagar, Bhushan

2009-01-01

The MIF4G domain of DAP5 was crystallized in two distinct crystal forms. Diffraction patterns have been analyzed and preliminary analysis, including molecular replacement, is presented here. Death-associated protein 5 (DAP5) is a member of the eIF4G family of scaffolding proteins that mediate cap-independent translation initiation by recruiting the translational machinery to internal ribosomal entry sites (IRESs) on mRNA. The MIF4G domain of DAP5 directly interacts with the eukaryotic initiation factors eIF4A and eIF3 and enhances the translation of several viral and cellular IRESs. Here, the crystallization and preliminary X-ray diffraction analysis of the MIF4G domain of DAP5 is presented
Origins of robustness in translational control via eukaryotic translation initiation factor (eIF) 2.

Science.gov (United States)

Khan, Mohammad Farhan; Spurgeon, Sarah; von der Haar, Tobias

2018-05-14

Phosphorylation of eukaryotic translation initiation factor 2 (eIF2) is one of the best studied and most widely used means for regulating protein synthesis activity in eukaryotic cells. This pathway regulates protein synthesis in response to stresses, viral infections, and nutrient depletion, among others. We present analyses of an ordinary differential equation-based model of this pathway, which aim to identify its principal robustness-conferring features. Our analyses indicate that robustness is a distributed property, rather than arising from the properties of any one individual pathway species. However, robustness-conferring properties are unevenly distributed between the different species, and we identify a guanine nucleotide dissociation inhibitor (GDI) complex as a species that likely contributes strongly to the robustness of the pathway. Our analyses make further predictions on the dynamic response to different types of kinases that impinge on eIF2. Copyright © 2018 Elsevier Ltd. All rights reserved.
A Novel Quality Measure and Correction Procedure for the Annotation of Microbial Translation Initiation Sites

NARCIS (Netherlands)

Overmars, L.; Siezen, R.J.; Francke, C.

2015-01-01

The identification of translation initiation sites (TISs) constitutes an important aspect of sequence-based genome analysis. An erroneous TIS annotation can impair the identification of regulatory elements and N-terminal signal peptides, and also may flaw the determination of descent, for any
Biological insights into the expression of translation initiation factors from recombinant CHOK1SV cell lines and their relationship to enhanced productivity.

Science.gov (United States)

Mead, Emma J; Masterton, Rosalyn J; Feary, Marc; Obrezanova, Olga; Zhang, Lin; Young, Robert; Smales, C Mark

2015-12-15

Translation initiation is on the critical pathway for the production of monoclonal antibodies (mAbs) by mammalian cells. Formation of a closed loop structure comprised of mRNA, a number of eukaryotic initiation factors (eIFs) and ribosomal proteins has been proposed to aid re-initiation of translation and therefore increase global translational efficiency. We have determined mRNA and protein levels of the key components of the closed loop, eIFs (eIF3a, eIF3b, eIF3c, eIF3h, eIF3i and eIF4G1), poly(A)-binding protein (PABP) 1 and PABP-interacting protein 1 (PAIP1), across a panel of 30 recombinant mAb-producing GS-CHOK1SV cell lines with a broad range of growth characteristics and production levels of a model recombinant mAb. We have used a multi-level statistical approach to investigate the relationship between key performance indicators (cell growth and recombinant antibody productivity) and the intracellular amounts of target translation initiation factor proteins and the mRNAs encoding them. We show that high-producing cell lines maintain amounts of the translation initiation factors involved in the formation of the closed loop mRNA, maintaining these proteins at appropriate levels to deliver enhanced recombinant protein production. We then utilize knowledge of the amounts of these factors to build predictive models for and use cluster analysis to identify, high-producing cell lines. The present study therefore defines the translation initiation factor amounts that are associated with highly productive recombinant GS-CHOK1SV cell lines that may be targets for screening highly productive cell lines or to engineer new host cell lines with the potential for enhanced recombinant antibody productivity. © 2015 Authors; published by Portland Press Limited.
Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS).

Science.gov (United States)

Kuemmerle-Deschner, Jasmin B; Ozen, Seza; Tyrrell, Pascal N; Kone-Paut, Isabelle; Goldbach-Mansky, Raphaela; Lachmann, Helen; Blank, Norbert; Hoffman, Hal M; Weissbarth-Riedel, Elisabeth; Hugle, Boris; Kallinich, Tilmann; Gattorno, Marco; Gul, Ahmet; Ter Haar, Nienke; Oswald, Marlen; Dedeoglu, Fatma; Cantarini, Luca; Benseler, Susanne M

2017-06-01

Cryopyrin-associated periodic syndrome (CAPS) is a rare, heterogeneous disease entity associated with NLRP3 gene mutations and increased interleukin-1 (IL-1) secretion. Early diagnosis and rapid initiation of IL-1 inhibition prevent organ damage. The aim of the study was to develop and validate diagnostic criteria for CAPS. An innovative process was followed including interdisciplinary team building, item generation: review of CAPS registries, systematic literature review, expert surveys, consensus conferences for item refinement, item reduction and weighting using 1000Minds decision software. Resulting CAPS criteria were tested in large cohorts of CAPS cases and controls using correspondence analysis. Diagnostic models were explored using sensitivity analyses. The international team included 16 experts. Systematic literature and registry review identified 33 CAPS-typical items; the consensus conferences reduced these to 14. 1000Minds exercises ranked variables based on importance for the diagnosis. Correspondence analysis determined variables consistently associated with the diagnosis of CAPS using 284 cases and 837 controls. Seven variables were significantly associated with CAPS (pCAPS-typical symptoms: urticaria-like rash, cold-triggered episodes, sensorineural hearing loss, musculoskeletal symptoms, chronic aseptic meningitis and skeletal abnormalities. Sensitivity was 81%, specificity 94%. It performed well for all CAPS subtypes and regardless of NLRP3 mutation. The novel approach integrated traditional methods of evidence synthesis with expert consensus, web-based decision tools and innovative statistical methods and may serve as model for other rare diseases. These criteria will enable a rapid diagnosis for children and adults with CAPS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Initiatives and evaluation of teaching-learning process in translation training

OpenAIRE

Olvera Lobo, Mar??a Dolores; Guti??rrez-Artacho, Juncal

2010-01-01

The ability to manage information and communication technologies (ICT) is a professional prerequisite for translators. The translation discipline is aware of this trend because ICTs have changed and developed the translation profession. Translation training is more than just learning a proficient command of languages, and translators must also develop other important skills ??? such as accessing and managing information resources. A group of teachers from various departments of the Univers...
Nat1 promotes translation of specific proteins that induce differentiation of mouse embryonic stem cells.

Science.gov (United States)

Sugiyama, Hayami; Takahashi, Kazutoshi; Yamamoto, Takuya; Iwasaki, Mio; Narita, Megumi; Nakamura, Masahiro; Rand, Tim A; Nakagawa, Masato; Watanabe, Akira; Yamanaka, Shinya

2017-01-10

Novel APOBEC1 target 1 (Nat1) (also known as "p97," "Dap5," and "Eif4g2") is a ubiquitously expressed cytoplasmic protein that is homologous to the C-terminal two thirds of eukaryotic translation initiation factor 4G (Eif4g1). We previously showed that Nat1-null mouse embryonic stem cells (mES cells) are resistant to differentiation. In the current study, we found that NAT1 and eIF4G1 share many binding proteins, such as the eukaryotic translation initiation factors eIF3 and eIF4A and ribosomal proteins. However, NAT1 did not bind to eIF4E or poly(A)-binding proteins, which are critical for cap-dependent translation initiation. In contrast, compared with eIF4G1, NAT1 preferentially interacted with eIF2, fragile X mental retardation proteins (FMR), and related proteins and especially with members of the proline-rich and coiled-coil-containing protein 2 (PRRC2) family. We also found that Nat1-null mES cells possess a transcriptional profile similar, although not identical, to the ground state, which is established in wild-type mES cells when treated with inhibitors of the ERK and glycogen synthase kinase 3 (GSK3) signaling pathways. In Nat1-null mES cells, the ERK pathway is suppressed even without inhibitors. Ribosome profiling revealed that translation of mitogen-activated protein kinase kinase kinase 3 (Map3k3) and son of sevenless homolog 1 (Sos1) is suppressed in the absence of Nat1 Forced expression of Map3k3 induced differentiation of Nat1-null mES cells. These data collectively show that Nat1 is involved in the translation of proteins that are required for cell differentiation.
Spanish translation Questionnaire of the Developmental Coordination Disorder

Directory of Open Access Journals (Sweden)

Salamanca LM

2012-05-01

Full Text Available The developmental coordination disorder can be recognized by motor difficulties that affect the performance in daily and school activities; therefore, it is necessary to get its early diagnosis in order to initiate early intervention. A tool for diagnosis is the Developmental coordination disorder questionnaire’07, DCDQ’07. Objective: the translation and cultural adaptation of the DCDQ’07 into Spanish. Materials and methods: three independent translators translated the questionnaire into Spanish. Its items were classified according to their equivalent or non-equivalent problems in some words, and also according to their experiential, semantic, conceptual or idioms equivalence. Results: 8 items out of 15 questionnaire items were classified as equivalent 8, 6 of them presented problems in a few words and only one was classified as non-equivalent, 10 items correspond to experiential equivalence translation, 4 items were classified as semantic equivalent and only one got two equivalents. The author agreed the Spanish version. Also, the parent´s opinions about the questionnaire were positive. Conclusions: most of the items of the questionnaire did not have translation difficulties. It allowed its translation and cultural adaptation into Spanish as well as its validation continuity and reliability process
Controlling contamination in Mo/Si multilayer mirrors by Si surface capping modifications

Science.gov (United States)

Malinowski, Michael E.; Steinhaus, Chip; Clift, W. Miles; Klebanoff, Leonard E.; Mrowka, Stanley; Soufli, Regina

2002-07-01

The performance of Mo/Si multilayer mirrors (MLMs) used to reflect UV (EUV) radiation in an EUV + hydrocarbon (NC) vapor environment can be improved by optimizing the silicon capping layer thickness on the MLM in order to minimize the initial buildup of carbon on MLMs. Carbon buildup is undesirable since it can absorb EUV radiation and reduce MLM reflectivity. A set of Mo/Si MLMs deposited on Si wafers was fabricated such that each MLM had a different Si capping layer thickness ranging form 2 nm to 7 nm. Samples from each MLM wafer were exposed to a combination of EUV light + (HC) vapors at the Advanced Light Source (ALS) synchrotron in order to determine if the Si capping layer thickness affected the carbon buildup on the MLMs. It was found that the capping layer thickness had a major influence on this 'carbonizing' tendency, with the 3 nm layer thickness providing the best initial resistance to carbonizing and accompanying EUV reflectivity loss in the MLM. The Si capping layer thickness deposited on a typical EUV optic is 4.3 nm. Measurements of the absolute reflectivities performed on the Calibration and Standards beamline at the ALS indicated the EUV reflectivity of the 3 nm-capped MLM was actually slightly higher than that of the normal, 4 nm Si-capped sample. These results show that he use of a 3 nm capping layer represents an improvement over the 4 nm layer since the 3 nm has both a higher absolute reflectivity and better initial resistance to carbon buildup. The results also support the general concept of minimizing the electric field intensity at the MLM surface to minimize photoelectron production and, correspondingly, carbon buildup in a EUV + HC vapor environment.
Cervical Cap

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... giving birth vaginally, which means the cervical cap may not fit as well. Inconsistent or incorrect use of the cervical cap increases your risk of pregnancy. For example, you may get pregnant when using the cervical cap if: ...
78 FR 22490 - Administrative Practice and Procedure; Postal Service; Review of Price Cap Rules

Science.gov (United States)

2013-04-16

...] Administrative Practice and Procedure; Postal Service; Review of Price Cap Rules AGENCY: Postal Regulatory Commission. ACTION: Proposed rule. SUMMARY: The Commission is initiating a review of its Price Cap Rules. The... implemented without a price cap calculation. Docket No. R2011-5, Order Approving Market Dominant Price...
Completion of the first TRT End-cap

CERN Multimedia

Catinaccio, A; Rohne, O

On July 1, the first end-cap of the ATLAS Transition Radiation Tracker (TRT) was successfully completed in terms of the integration of the wheels assembled in Russia with their front-end electronics. The two groups of the detector, fully assembled and equipped with front-end electronics, were rotated from their horizontal position during stacking to their nominal vertical position, in which they will be integrated with the corresponding end-cap silicon-strip (SCT) detector towards the end of 2005, before installation into ATLAS in spring 2006. After starting the assembly in the SR building one year ago, the TRT team reached this important milestone, which marks the final realization and validation of the engineering concept developed by the CERN DT1 (ex-TA1) and ATT teams. A TRT end-cap consists of two sets of identical and independent wheels. The first type of wheels (type A, 12 wheels, positioned closest to the primary interaction point) contains 6144 radial straws positioned in eight successive layers s...
PKC δ Regulates Translation Initiation through PKR and eIF2 α in Response to Retinoic Acid in Acute Myeloid Leukemia Cells

OpenAIRE

Ozpolat, Bulent; Akar, Ugur; Tekedereli, Ibrahim; Alpay, S. Neslihan; Barria, Magaly; Gezgen, Baki; Zhang, Nianxiang; Coombes, Kevin; Kornblau, Steve; Lopez-Berestein, Gabriel

2012-01-01

Translation initiation and activity of eukaryotic initiation factor-alpha (eIF2 α ), the rate-limiting step of translation initiation, is often overactivated in malignant cells. Here, we investigated the regulation and role of eIF2 α in acute promyelocytic (APL) and acute myeloid leukemia (AML) cells in response to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), the front-line therapies in APL. ATRA and ATO induce Ser-51 phosphorylation (inactivation) of eIF2 α , through the induct...
N-terminal Proteomics Assisted Profiling of the Unexplored Translation Initiation Landscape in Arabidopsis thaliana.

Science.gov (United States)

Willems, Patrick; Ndah, Elvis; Jonckheere, Veronique; Stael, Simon; Sticker, Adriaan; Martens, Lennart; Van Breusegem, Frank; Gevaert, Kris; Van Damme, Petra

2017-06-01

Proteogenomics is an emerging research field yet lacking a uniform method of analysis. Proteogenomic studies in which N-terminal proteomics and ribosome profiling are combined, suggest that a high number of protein start sites are currently missing in genome annotations. We constructed a proteogenomic pipeline specific for the analysis of N-terminal proteomics data, with the aim of discovering novel translational start sites outside annotated protein coding regions. In summary, unidentified MS/MS spectra were matched to a specific N-terminal peptide library encompassing protein N termini encoded in the Arabidopsis thaliana genome. After a stringent false discovery rate filtering, 117 protein N termini compliant with N-terminal methionine excision specificity and indicative of translation initiation were found. These include N-terminal protein extensions and translation from transposable elements and pseudogenes. Gene prediction provided supporting protein-coding models for approximately half of the protein N termini. Besides the prediction of functional domains (partially) contained within the newly predicted ORFs, further supporting evidence of translation was found in the recently released Araport11 genome re-annotation of Arabidopsis and computational translations of sequences stored in public repositories. Most interestingly, complementary evidence by ribosome profiling was found for 23 protein N termini. Finally, by analyzing protein N-terminal peptides, an in silico analysis demonstrates the applicability of our N-terminal proteogenomics strategy in revealing protein-coding potential in species with well- and poorly-annotated genomes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Digital hologram transformations for RGB color holographic display with independent image magnification and translation in 3D.

Science.gov (United States)

Makowski, Piotr L; Zaperty, Weronika; Kozacki, Tomasz

2018-01-01

A new framework for in-plane transformations of digital holograms (DHs) is proposed, which provides improved control over basic geometrical features of holographic images reconstructed optically in full color. The method is based on a Fourier hologram equivalent of the adaptive affine transformation technique [Opt. Express18, 8806 (2010)OPEXFF1094-408710.1364/OE.18.008806]. The solution includes four elementary geometrical transformations that can be performed independently on a full-color 3D image reconstructed from an RGB hologram: (i) transverse magnification; (ii) axial translation with minimized distortion; (iii) transverse translation; and (iv) viewing angle rotation. The independent character of transformations (i) and (ii) constitutes the main result of the work and plays a double role: (1) it simplifies synchronization of color components of the RGB image in the presence of mismatch between capture and display parameters; (2) provides improved control over position and size of the projected image, particularly the axial position, which opens new possibilities for efficient animation of holographic content. The approximate character of the operations (i) and (ii) is examined both analytically and experimentally using an RGB circular holographic display system. Additionally, a complex animation built from a single wide-aperture RGB Fourier hologram is presented to demonstrate full capabilities of the developed toolset.
Denoising of chaotic signal using independent component analysis and empirical mode decomposition with circulate translating

International Nuclear Information System (INIS)

Wang Wen-Bo; Zhang Xiao-Dong; Chang Yuchan; Wang Xiang-Li; Wang Zhao; Chen Xi; Zheng Lei

2016-01-01

In this paper, a new method to reduce noises within chaotic signals based on ICA (independent component analysis) and EMD (empirical mode decomposition) is proposed. The basic idea is decomposing chaotic signals and constructing multidimensional input vectors, firstly, on the base of EMD and its translation invariance. Secondly, it makes the independent component analysis on the input vectors, which means that a self adapting denoising is carried out for the intrinsic mode functions (IMFs) of chaotic signals. Finally, all IMFs compose the new denoised chaotic signal. Experiments on the Lorenz chaotic signal composed of different Gaussian noises and the monthly observed chaotic sequence on sunspots were put into practice. The results proved that the method proposed in this paper is effective in denoising of chaotic signals. Moreover, it can correct the center point in the phase space effectively, which makes it approach the real track of the chaotic attractor. (paper)
Gemin5: A Multitasking RNA-Binding Protein Involved in Translation Control

Directory of Open Access Journals (Sweden)

David Piñeiro

2015-04-01

Full Text Available Gemin5 is a RNA-binding protein (RBP that was first identified as a peripheral component of the survival of motor neurons (SMN complex. This predominantly cytoplasmic protein recognises the small nuclear RNAs (snRNAs through its WD repeat domains, allowing assembly of the SMN complex into small nuclear ribonucleoproteins (snRNPs. Additionally, the amino-terminal end of the protein has been reported to possess cap-binding capacity and to interact with the eukaryotic initiation factor 4E (eIF4E. Gemin5 was also shown to downregulate translation, to be a substrate of the picornavirus L protease and to interact with viral internal ribosome entry site (IRES elements via a bipartite non-canonical RNA-binding site located at its carboxy-terminal end. These features link Gemin5 with translation control events. Thus, beyond its role in snRNPs biogenesis, Gemin5 appears to be a multitasking protein cooperating in various RNA-guided processes. In this review, we will summarise current knowledge of Gemin5 functions. We will discuss the involvement of the protein on translation control and propose a model to explain how the proteolysis fragments of this RBP in picornavirus-infected cells could modulate protein synthesis.
Anti-pp,. cap alpha cap alpha. and p. cap alpha. elastic scattering at high energies and Chou-Yang conjecture

Energy Technology Data Exchange (ETDEWEB)

Saleem, M.; Fazal-e-Aleem; Rifique, M.

1987-03-01

The recent experimental measurements for anti-pp and ..cap alpha cap alpha.. elastic scattering at high energies have shown that the Chou-Yang conjecture regarding the relationship between the electromagnetic and the hadronic form factor of a particle is only an approximation. A new ansatz has been proposed to obtain hadronic form factors of proton and the ..cap alpha..-particle. These form factors have been used to explain the various characteristics of anti-pp, ..cap alpha cap alpha.. and p..cap alpha.. elastic scattering at high energies.
Analysis of RNA binding by the dengue virus NS5 RNA capping enzyme.

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Brittney R Henderson

Full Text Available Flaviviruses are small, capped positive sense RNA viruses that replicate in the cytoplasm of infected cells. Dengue virus and other related flaviviruses have evolved RNA capping enzymes to form the viral RNA cap structure that protects the viral genome and directs efficient viral polyprotein translation. The N-terminal domain of NS5 possesses the methyltransferase and guanylyltransferase activities necessary for forming mature RNA cap structures. The mechanism for flavivirus guanylyltransferase activity is currently unknown, and how the capping enzyme binds its diphosphorylated RNA substrate is important for deciphering how the flavivirus guanylyltransferase functions. In this report we examine how flavivirus NS5 N-terminal capping enzymes bind to the 5' end of the viral RNA using a fluorescence polarization-based RNA binding assay. We observed that the K(D for RNA binding is approximately 200 nM Dengue, Yellow Fever, and West Nile virus capping enzymes. Removal of one or both of the 5' phosphates reduces binding affinity, indicating that the terminal phosphates contribute significantly to binding. RNA binding affinity is negatively affected by the presence of GTP or ATP and positively affected by S-adensyl methoninine (SAM. Structural superpositioning of the dengue virus capping enzyme with the Vaccinia virus VP39 protein bound to RNA suggests how the flavivirus capping enzyme may bind RNA, and mutagenesis analysis of residues in the putative RNA binding site demonstrate that several basic residues are critical for RNA binding. Several mutants show differential binding to 5' di-, mono-, and un-phosphorylated RNAs. The mode of RNA binding appears similar to that found with other methyltransferase enzymes, and a discussion of diphosphorylated RNA binding is presented.
Stimulation of muscle protein synthesis by somatotropin in pigs is independent of the somatotropin-induced increase in circulating insulin.

Science.gov (United States)

Wilson, Fiona A; Orellana, Renán A; Suryawan, Agus; Nguyen, Hanh V; Jeyapalan, Asumthia S; Frank, Jason; Davis, Teresa A

2008-07-01

Chronic treatment of growing pigs with porcine somatotropin (pST) promotes protein synthesis and doubles postprandial levels of insulin, a hormone that stimulates translation initiation. This study aimed to determine whether the pST-induced increase in skeletal muscle protein synthesis was mediated through an insulin-induced stimulation of translation initiation. After 7-10 days of pST (150 microg x kg(-1) x day(-1)) or control saline treatment, pancreatic glucose-amino acid clamps were performed in overnight-fasted pigs to reproduce 1) fasted (5 microU/ml), 2) fed control (25 microU/ml), and 3) fed pST-treated (50 microU/ml) insulin levels while glucose and amino acids were maintained at baseline fasting levels. Fractional protein synthesis rates and indexes of translation initiation were examined in skeletal muscle. Effectiveness of pST treatment was confirmed by reduced urea nitrogen and elevated insulin-like growth factor I levels in plasma. Skeletal muscle protein synthesis was independently increased by both insulin and pST. Insulin increased the phosphorylation of protein kinase B and the downstream effectors of the mammalian target of rapamycin, ribosomal protein S6 kinase, and eukaryotic initiation factor (eIF)4E-binding protein-1 (4E-BP1). Furthermore, insulin reduced inactive 4E-BP1.eIF4E complex association and increased active eIF4E.eIF4G complex formation, indicating enhanced eIF4F complex assembly. However, pST treatment did not alter translation initiation factor activation. We conclude that the pST-induced stimulation of skeletal muscle protein synthesis in growing pigs is independent of the insulin-associated activation of translation initiation.
Photoactivable caps for reactive metal nanoparticles

Science.gov (United States)

Patel, Ashish

The synthesis and stabilization of reactive metal nanoparticles is often challenging under normal atmospheric conditions. This problem can be alleviated by capping and passivation. Our lab has focused on forming polymer coatings on the surface of reactive metal nanoparticles. We discovered a convenient and effective route for stabilization of aluminum nanoparticles (Al NPs), which uses the nascent metal core as a polymerization initiator for various organic monomers. In our previous work, we used this method to passivate the Al NPs using variety of epoxides and copolymers of epoxides and alkenes. These products have demonstrated air stability for weeks to months with little to no degradation in the active Al content. Since our previously synthesized Al NP's were not beneficial for rapid and efficient thermodynamic access to the active Al core, our goal was find polymers that could easily be photochemically activated to enhance such access. Since poly(methyl methacrylate) (PMMA) has photodegrading properties, we used PMMA as a capping agent to passivate Al NPs. In this work, we present capping and stabilization of Al NPs with PMMA, and also with 1,2-epoxyhexane/ PMMA. In our previous work, we increased the stability of Al NP capped with 1,2-epoxy-9-decene by adding 1,13-tetradecadiene as a cross-linker. Here, we used the methyl methacrylate (MMA) monomer as cross-linker for Al NP capped with 1,2-epoxy-9-decene. We have also used the MMA as capping agent. We use powder x-ray diffractametry (PXRD), differential scanning calorimetry (DSC), and thermogravity analysis (TGA) to confirm the presence of elemental Al and ATR-FTIR to confirm the presence of polymers.
The influence of a Si cap on self-organized SiGe islands and the underlying wetting layer

International Nuclear Information System (INIS)

Brehm, M.; Grydlik, M.; Groiss, H.; Hackl, F.; Schaeffler, F.; Fromherz, T.; Bauer, G.

2011-01-01

For the prototypical SiGe/Si(001) Stranski-Krastanow (SK) growth system, the influence of intermixing caused by the deposition of a Si cap layer at temperatures T cap between 300 deg. C and 700 deg. C is studied both for the SiGe wetting layer (WL) and the SiGe islands. Systematic growth experiments were carried out with an ultrahigh resolution of down to 0.005 monolayers (ML) of deposited Ge. The properties of the samples were investigated via photoluminescence (PL) spectroscopy, atomic force microscopy (AFM), and transmission electron microscopy. We studied in detail the influence of T cap in the three main coverage regions of SiGe SK growth, which are (i) the WL build-up regime, (ii) the island nucleation regime, where most of the Ge is supplied via material transfer from the WL, and (iii) the saturation regime, where the WL thickness remains initially stable. At T cap = 300 deg. C, we found that both the WL and the island are essentially preserved in composition and shape, whereas at 500 deg. C the WL becomes heavily alloyed during capping, and at 700 deg. C the islands also become alloyed. At T cap = 500 deg. C we found enhanced WL intermixing in the presence of dome-shaped islands, whereas at T cap 700 deg. C the WL properties become dominated by the dissolution of pyramid-shaped islands upon capping. At Ge coverages above ≅6 ML, we found an unexpected thickening of the WL, almost independently of T cap . This finding suggests that the density and the volume of the dome-shaped islands have an upper limit, beyond which excess Ge from the external source again becomes incorporated into the WL. Finally, we compared PL spectra with AFM-based evaluations of the integral island volumes in order to determine in a straightforward manner the average composition of the SiGe islands.
Protein Translation and Signaling in Human Eosinophils

Directory of Open Access Journals (Sweden)

Stephane Esnault

2017-09-01

Full Text Available We have recently reported that, unlike IL-5 and GM-CSF, IL-3 induces increased translation of a subset of mRNAs. In addition, we have demonstrated that Pin1 controls the activity of mRNA binding proteins, leading to enhanced mRNA stability, GM-CSF protein production and prolonged eosinophil (EOS survival. In this review, discussion will include an overview of cap-dependent protein translation and its regulation by intracellular signaling pathways. We will address the more general process of mRNA post-transcriptional regulation, especially regarding mRNA binding proteins, which are critical effectors of protein translation. Furthermore, we will focus on (1 the roles of IL-3-driven sustained signaling on enhanced protein translation in EOS, (2 the mechanisms regulating mRNA binding proteins activity in EOS, and (3 the potential targeting of IL-3 signaling and the signaling leading to mRNA binding activity changes to identify therapeutic targets to treat EOS-associated diseases.
Cradle Cap (For Parents)

Science.gov (United States)

... Safe Videos for Educators Search English Español Cradle Cap (Infantile Seborrheic Dermatitis) KidsHealth / For Parents / Cradle Cap ( ... many babies develop called cradle cap. About Cradle Cap Cradle cap is the common term for seborrheic ...
The NS1 Protein from Influenza Virus Stimulates Translation Initiation by Enhancing Ribosome Recruitment to mRNAs.

Science.gov (United States)

Panthu, Baptiste; Terrier, Olivier; Carron, Coralie; Traversier, Aurélien; Corbin, Antoine; Balvay, Laurent; Lina, Bruno; Rosa-Calatrava, Manuel; Ohlmann, Théophile

2017-10-27

The non-structural protein NS1 of influenza A viruses exerts pleiotropic functions during infection. Among these functions, NS1 was shown to be involved in the control of both viral and cellular translation; however, the mechanism by which this occurs remains to be determined. Thus, we have revisited the role of NS1 in translation by using a combination of influenza infection, mRNA reporter transfection, and in vitro functional and biochemical assays. Our data show that the NS1 protein is able to enhance the translation of virtually all tested mRNAs with the exception of constructs bearing the Dicistroviruses Internal ribosome entry segment (IRESes) (DCV and CrPV), suggesting a role at the level of translation initiation. The domain of NS1 required for translation stimulation was mapped to the RNA binding amino-terminal motif of the protein with residues R38 and K41 being critical for activity. Although we show that NS1 can bind directly to mRNAs, it does not correlate with its ability to stimulate translation. This activity rather relies on the property of NS1 to associate with ribosomes and to recruit them to target mRNAs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Alba-domain proteins of Trypanosoma brucei are cytoplasmic RNA-binding proteins that interact with the translation machinery.

Directory of Open Access Journals (Sweden)

Jan Mani

Full Text Available Trypanosoma brucei and related pathogens transcribe most genes as polycistronic arrays that are subsequently processed into monocistronic mRNAs. Expression is frequently regulated post-transcriptionally by cis-acting elements in the untranslated regions (UTRs. GPEET and EP procyclins are the major surface proteins of procyclic (insect midgut forms of T. brucei. Three regulatory elements common to the 3' UTRs of both mRNAs regulate mRNA turnover and translation. The glycerol-responsive element (GRE is unique to the GPEET 3' UTR and regulates its expression independently from EP. A synthetic RNA encompassing the GRE showed robust sequence-specific interactions with cytoplasmic proteins in electromobility shift assays. This, combined with column chromatography, led to the identification of 3 Alba-domain proteins. RNAi against Alba3 caused a growth phenotype and reduced the levels of Alba1 and Alba2 proteins, indicative of interactions between family members. Tandem-affinity purification and co-immunoprecipitation verified these interactions and also identified Alba4 in sub-stoichiometric amounts. Alba proteins are cytoplasmic and are recruited to starvation granules together with poly(A RNA. Concomitant depletion of all four Alba proteins by RNAi specifically reduced translation of a reporter transcript flanked by the GPEET 3' UTR. Pulldown of tagged Alba proteins confirmed interactions with poly(A binding proteins, ribosomal protein P0 and, in the case of Alba3, the cap-binding protein eIF4E4. In addition, Alba2 and Alba3 partially cosediment with polyribosomes in sucrose gradients. Alba-domain proteins seem to have exhibited great functional plasticity in the course of evolution. First identified as DNA-binding proteins in Archaea, then in association with nuclear RNase MRP/P in yeast and mammalian cells, they were recently described as components of a translationally silent complex containing stage-regulated mRNAs in Plasmodium. Our results are
Initial 12-h operative fluid volume is an independent risk factor for pleural effusion after hepatectomy.

Science.gov (United States)

Cheng, Xiang; Wu, Jia-Wei; Sun, Ping; Song, Zi-Fang; Zheng, Qi-Chang

2016-12-01

Pleural effusion after hepatectomy is associated with significant morbidity and prolonged hospital stays. Several studies have addressed the risk factors for postoperative pleural effusion. However, there are no researches concerning the role of the initial 12-h operative fluid volume. The aim of this study was to evaluate whether the initial 12-h operative fluid volume during liver resection is an independent risk factor for pleural effusion after hepatectomy. In this study, we retrospectively analyzed clinical data of 470 patients consecutively undergoing elective hepatectomy between January 2011 and December 2012. We prospectively collected and retrospectively analyzed baseline and clinical data, including preoperative, intraoperative, and postoperative variables. Univariate and multivariate analyses were carried out to identify whether the initial 12-h operative fluid volume was an independent risk factor for pleural effusion after hepatectomy. The multivariate analysis identified 2 independent risk factors for pleural effusion: operative time [odds ratio (OR)=10.2] and initial 12-h operative fluid volume (OR=1.0003). Threshold effect analyses revealed that the initial 12 h operative fluid volume was positively correlated with the incidence of pleural effusion when the initial 12-h operative fluid volume exceeded 4636 mL. We conclude that the initial 12-h operative fluid volume during liver resection and operative time are independent risk factors for pleural effusion after hepatectomy. Perioperative intravenous fluids should be restricted properly.
Excessive Cap-dependent Translation as a Molecular Mechanism Underlying ASD

Science.gov (United States)

2014-10-01

Frankfurt, Germany 6) Adler Lecture, 30th Annual Retreat, Mahoney Institute for Neurosciences, University of Pennsylvania, Philadelphia... Deregulation of EIF4E: a novel mechanism for autism. J. Med. Genet. 46, 759–765 (2009). 7. Ruggero, D. et al. The translation factor eIF-4E promotes...Hughes, S. B. Shen, D. S. Clair, Z. Miedzybrodzka, Deregulation of EIF4E: A novel mechanism for autism. J. Med. Genet. 46, 759–765 (2009). 48. E. Klann
Activation by insulin and amino acids of signaling components leading to translation initiation in skeletal muscle of neonatal pigs is developmentally regulated.

Science.gov (United States)

Suryawan, Agus; Orellana, Renan A; Nguyen, Hanh V; Jeyapalan, Asumthia S; Fleming, Jillian R; Davis, Teresa A

2007-12-01

Insulin and amino acids act independently to stimulate protein synthesis in skeletal muscle of neonatal pigs, and the responses decrease with development. The purpose of this study was to compare the separate effects of fed levels of INS and AA on the activation of signaling components leading to translation initiation and how these responses change with development. Overnight-fasted 6- (n = 4/group) and 26-day-old (n = 6/ group) pigs were studied during 1) euinsulinemic-euglycemiceuaminoacidemic conditions (controls), 2) euinsulinemic-euglycemichyperaminoacidemic clamps (AA), and 3) hyperinsulinemic-euglycemic-euaminoacidemic clamps (INS). INS, but not AA, increased the phosphorylation of protein kinase B (PKB) and tuberous sclerosis 2 (TSC2). Both INS and AA increased protein synthesis and the phosphorylation of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase-1, and eukaryotic initiation factor (eIF)4E-binding protein 1 (4E-BP1), and these responses were higher in 6-day-old compared with 26-day-old pigs. Both INS and AA decreased the binding of 4E-BP1 to eIF4E and increased eIF4E binding to eIF4G; these effects were greater in 6-day-old than in 26-day-old pigs. Neither INS nor AA altered the composition of mTORC1 (raptor, mTOR, and GbetaL) or mTORC2 (rictor, mTOR, and GbetaL) complexes. Furthermore, neither INS, AA, nor age had any effect on the abundance of Rheb and the phosphorylation of AMP-activated protein kinase and eukaryotic elongation factor 2. Our results suggest that the activation by insulin and amino acids of signaling components leading to translation initiation is developmentally regulated and parallels the developmental decline in protein synthesis in skeletal muscle of neonatal pigs.
Understanding Career Success and Its Contributing Factors for Clinical and Translational Investigators

Science.gov (United States)

Robinson, Georgeanna F.W.B.; Schwartz, Lisa S.; DiMeglio, Linda A.; Ahluwalia, Jasjit S.; Gabrilove, Janice L.

2015-01-01

Purpose To understand the factors that facilitate career success for career development awardees in clinical and translational science and to reconceptualize understanding of career success for this population. Method In 2013–2014, the authors conducted semi-structured interviews with former NIH KL2 or K12 scholars from nine Clinical and Translational Science Award-funded institutions. Participants either had or had not secured independent funding at least two years after the end of their last K award. Questions covered the factors that facilitate or hinder junior investigators’ transition to independent funding. Interviews were recorded and transcribed and the transcripts analyzed thematically. Results Forty individuals participated, with equal representation by men and women and by independently and not independently funded investigators. Personal factors that facilitated success included: networks, persistence and resilience, initiative, autonomy, and personal and professional balance. Organizational factors included: appropriate mentorship, protected research time, and institutional resources and support. Even independently funded participants described challenges regarding career direction. Five participants without independent funding modeled a broad spectrum of successful career paths, having assumed leadership positions not reliant on grant funding. Alternative definitions of career success included: improving public health, enjoying work, seeing mentees succeed, and receiving external acknowledgement of successes. Conclusions Awareness of the factors that facilitate or hinder career success can help junior faculty, mentors, and institutional leaders support career development in clinical and translational science. New definitions of career success are needed, as are career paths for faculty who want to engage in research in roles other than principal investigator. PMID:26509600
Towards a classification of translation styles based on eye-tracking and keylogging data

Directory of Open Access Journals (Sweden)

Barbara Dragsted & Michael Carl

2013-06-01

Full Text Available This article seeks to formulate translator profiles based on process data from keylogging and eye-tracking, while at the same time identifying features which are shared by all translators in a sample consisting of both students and professionals. Data have been collected from 12 professional translators and 12 graduate students translating three texts of varying complexity. We found that individual behavioural characteristics with respect to initial orientation in the source text (ST, online ST reading, and online and end revision remained relatively constant across texts of varying complexity, supporting our hypothesis that translator profiles can be observed which are independent of the difficulty of the translation task. The analysis of the data also indicated that translators could be grouped into broad categories of locally-oriented and globally-oriented translation styles, which are partly, though not entirely, comparable to styles known from writing research. We also identified shared features with respect to reading and revision behaviour during drafting. Common to all translators was that they looked beyond the source text word they were about to translate, and that they made revisions while drafting the translation.
Establishment of chronic hepatitis C virus infection: Translational evasion of oxidative defence

Science.gov (United States)

Chan, Shiu-Wan

2014-01-01

Hepatitis C virus (HCV) causes a clinically important disease affecting 3% of the world population. HCV is a single-stranded, positive-sense RNA virus belonging to the genus Hepacivirus within the Flaviviridae family. The virus establishes a chronic infection in the face of an active host oxidative defence, thus adaptation to oxidative stress is key to virus survival. Being a small RNA virus with a limited genomic capacity, we speculate that HCV deploys a different strategy to evade host oxidative defence. Instead of counteracting oxidative stress, it utilizes oxidative stress to facilitate its own survival. Translation is the first step in the replication of a plus strand RNA virus so it would make sense if the virus can exploit the host oxidative defence in facilitating this very first step. This is particularly true when HCV utilizes an internal ribosome entry site element in translation, which is distinctive from that of cap-dependent translation of the vast majority of cellular genes, thus allowing selective translation of genes under conditions when global protein synthesis is compromised. Indeed, we were the first to show that HCV translation was stimulated by an important pro-oxidant-hydrogen peroxide in hepatocytes, suggesting that HCV is able to adapt to and utilize the host anti-viral response to facilitate its own translation thus allowing the virus to thrive under oxidative stress condition to establish chronicity. Understanding how HCV translation is regulated under oxidative stress condition will advance our knowledge on how HCV establishes chronicity. As chronicity is the initiator step in disease progression this will eventually lead to a better understanding of pathogenicity, which is particularly relevant to the development of anti-virals and improved treatments of HCV patients using anti-oxidants. PMID:24659872
Establishment of chronic hepatitis C virus infection: translational evasion of oxidative defence.

Science.gov (United States)

Chan, Shiu-Wan

2014-03-21

Hepatitis C virus (HCV) causes a clinically important disease affecting 3% of the world population. HCV is a single-stranded, positive-sense RNA virus belonging to the genus Hepacivirus within the Flaviviridae family. The virus establishes a chronic infection in the face of an active host oxidative defence, thus adaptation to oxidative stress is key to virus survival. Being a small RNA virus with a limited genomic capacity, we speculate that HCV deploys a different strategy to evade host oxidative defence. Instead of counteracting oxidative stress, it utilizes oxidative stress to facilitate its own survival. Translation is the first step in the replication of a plus strand RNA virus so it would make sense if the virus can exploit the host oxidative defence in facilitating this very first step. This is particularly true when HCV utilizes an internal ribosome entry site element in translation, which is distinctive from that of cap-dependent translation of the vast majority of cellular genes, thus allowing selective translation of genes under conditions when global protein synthesis is compromised. Indeed, we were the first to show that HCV translation was stimulated by an important pro-oxidant-hydrogen peroxide in hepatocytes, suggesting that HCV is able to adapt to and utilize the host anti-viral response to facilitate its own translation thus allowing the virus to thrive under oxidative stress condition to establish chronicity. Understanding how HCV translation is regulated under oxidative stress condition will advance our knowledge on how HCV establishes chronicity. As chronicity is the initiator step in disease progression this will eventually lead to a better understanding of pathogenicity, which is particularly relevant to the development of anti-virals and improved treatments of HCV patients using anti-oxidants.
Mechanisms of translation control underlying long-lasting synaptic plasticity and the consolidation of long-term memory.

Science.gov (United States)

Santini, Emanuela; Huynh, Thu N; Klann, Eric

2014-01-01

The complexity of memory formation and its persistence is a phenomenon that has been studied intensely for centuries. Memory exists in many forms and is stored in various brain regions. Generally speaking, memories are reorganized into broadly distributed cortical networks over time through systems level consolidation. At the cellular level, storage of information is believed to initially occur via altered synaptic strength by processes such as long-term potentiation. New protein synthesis is required for long-lasting synaptic plasticity as well as for the formation of long-term memory. The mammalian target of rapamycin complex 1 (mTORC1) is a critical regulator of cap-dependent protein synthesis and is required for numerous forms of long-lasting synaptic plasticity and long-term memory. As such, the study of mTORC1 and protein factors that control translation initiation and elongation has enhanced our understanding of how the process of protein synthesis is regulated during memory formation. Herein we discuss the molecular mechanisms that regulate protein synthesis as well as pharmacological and genetic manipulations that demonstrate the requirement for proper translational control in long-lasting synaptic plasticity and long-term memory formation. © 2014 Elsevier Inc. All rights reserved.
Cradle Cap: Treatment

Science.gov (United States)

Cradle cap Treatment Cradle cap usually doesn't require medical treatment. It clears up on its own within a few months. In the meantime, wash ... tips can help you control and manage cradle cap. Gently rub your baby's scalp with your fingers ...
Pharmacogenetic Inhibition of eIF4E-Dependent Mmp9 mRNA Translation Reverses Fragile X Syndrome-like Phenotypes

Directory of Open Access Journals (Sweden)

Christos G. Gkogkas

2014-12-01

Full Text Available Summary: Fragile X syndrome (FXS is the leading genetic cause of autism. Mutations in Fmr1 (fragile X mental retardation 1 gene engender exaggerated translation resulting in dendritic spine dysmorphogenesis, synaptic plasticity alterations, and behavioral deficits in mice, which are reminiscent of FXS phenotypes. Using postmortem brains from FXS patients and Fmr1 knockout mice (Fmr1−/y, we show that phosphorylation of the mRNA 5′ cap binding protein, eukaryotic initiation factor 4E (eIF4E, is elevated concomitant with increased expression of matrix metalloproteinase 9 (MMP-9 protein. Genetic or pharmacological reduction of eIF4E phosphorylation rescued core behavioral deficits, synaptic plasticity alterations, and dendritic spine morphology defects via reducing exaggerated translation of Mmp9 mRNA in Fmr1−/y mice, whereas MMP-9 overexpression produced several FXS-like phenotypes. These results uncover a mechanism of regulation of synaptic function by translational control of Mmp-9 in FXS, which opens the possibility of new treatment avenues for the diverse neurological and psychiatric aspects of FXS. : Fragile X syndrome (FXS is caused by dysregulation of translation in the brain. Gkogkas et al. show that phosphorylation of eukaryotic translation initiation factor 4E (eIF4E is increased in FXS postmortem brains and Fmr1−/y mice. Downregulation of eIF4E phosphorylation in Fmr1−/y mice rescues defects in dendritic spine morphology, synaptic plasticity, and social interaction via normalization of MMP-9 expression.
Inhibition of Ribosome Recruitment Induces Stress Granule Formation Independently of Eukaryotic Initiation Factor 2α Phosphorylation

OpenAIRE

Mazroui, Rachid; Sukarieh, Rami; Bordeleau, Marie-Eve; Kaufman, Randal J.; Northcote, Peter; Tanaka, Junichi; Gallouzi, Imed; Pelletier, Jerry

2006-01-01

Cytoplasmic aggregates known as stress granules (SGs) arise as a consequence of cellular stress and contain stalled translation preinitiation complexes. These foci are thought to serve as sites of mRNA storage or triage during the cell stress response. SG formation has been shown to require induction of eukaryotic initiation factor (eIF)2α phosphorylation. Herein, we investigate the potential role of other initiation factors in this process and demonstrate that interfering with eIF4A activity...
Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

NARCIS (Netherlands)

Mugavero, Michael J; May, Margaret; Harris, Ross; Saag, Michael S; Costagliola, Dominique; Egger, Matthias; Phillips, Andrew; Günthard, Huldrych F; Dabis, Francois; Hogg, Robert; de Wolf, Frank; Fatkenheuer, Gerd; Gill, M John; Justice, Amy; D'Arminio Monforte, Antonella; Lampe, Fiona; Miró, Jose M; Staszewski, Schlomo; Sterne, Jonathan A C; Niesters, Bert

2008-01-01

OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between
Downregulation of viral RNA translation by hepatitis C virus non-structural protein NS5A requires the poly(U/UC) sequence in the 3' UTR.

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Hoffman, Brett; Li, Zhubing; Liu, Qiang

2015-08-01

Hepatitis C virus (HCV) non-structural protein 5A (NS5A) is essential for viral replication; however, its effect on HCV RNA translation remains controversial partially due to the use of reporters lacking the 3' UTR, where NS5A binds to the poly(U/UC) sequence. We investigated the role of NS5A in HCV translation using a monocistronic RNA containing a Renilla luciferase gene flanked by the HCV UTRs. We found that NS5A downregulated viral RNA translation in a dose-dependent manner. This downregulation required both the 5' and 3' UTRs of HCV because substitution of either sequence with the 5' and 3' UTRs of enterovirus 71 or a cap structure at the 5' end eliminated the effects of NS5A on translation. Translation of the HCV genomic RNA was also downregulated by NS5A. The inhibition of HCV translation by NS5A required the poly(U/UC) sequence in the 3' UTR as NS5A did not affect translation when it was deleted. In addition, we showed that, whilst the amphipathic α-helix of NS5A has no effect on viral translation, the three domains of NS5A can inhibit translation independently, also dependent on the presence of the poly(U/UC) sequence in the 3' UTR. These results suggested that NS5A downregulated HCV RNA translation through a mechanism involving the poly(U/UC) sequence in the 3' UTR.
Sepsis and mechnaical ventilation restrain translation initiation in skeletal muscle by inducing AMPK-associated TSC[2] restriction of mTOR signaling in pigs

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In skeletal muscle, AMP-activated protein kinase (AMPK) acts as a cellular energy sensor of AMP: ATP and modulates translation by repressing mammalian target of rapamycin (mTOR) activation. Endotoxin (LPS)-induced sepsis reduces muscle protein synthesis by blunting translation initiation. We hypothe...
CAPS--pathogenesis, presentation and treatment of an autoinflammatory disease.

Science.gov (United States)

Kuemmerle-Deschner, Jasmin B

2015-07-01

The cryopyrin-associated periodic syndrome (CAPS) is a severity spectrum of rare diseases. CAPS comprises the three conditions previously described as familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disorder (NOMID), also known as chronic infantile neurologic, cutaneous, and articular (CINCA) syndrome. The clinical phenotype of CAPS is characterized by systemic inflammation. General symptoms are fatigue and fever. Local manifestations affect multiple tissues such as skin, joints, muscles, eyes, and the central nervous system. Distinct clinical features are characteristic for each subphenotype. In FCAS, these are cold-induced urticaria and fever, in MWS systemic amyloidosis and hearing loss and in NOMID/CINCA central nervous system inflammation and bone deformities. CAPS is caused by single heterozygous germline or somatic gain of function mutations in the NLRP3 gene encoding the protein cryopyrin. Cryopyrin nucleates an NLRP3 inflammasome, which regulates the activation and cleavage of caspase-1 that cleaves the pro-inflammatory cytokines, IL-1β and IL-18. IL-1β plays the key role in the induction of inflammation in CAPS. This has been confirmed by the application of IL-1 blocking agents, which lead not only to a rapid and sustained reversal of daily symptoms but also to some extent of long-term disease sequelae. To prevent CAPS-induced organ damage, early diagnosis and swift initiation of effective treatment are mandatory.
A Protocol of Japanese-English Translation

OpenAIRE

三浦, 勲夫; MIURA, Isao

1999-01-01

Every year I translate Japanes enewspaper articles into English and publish them in book form containing 12 or more translations. In translating there are regular procedures I go through:1)initial translation done by me and 2) corrected translation done through discussion between a native English speaker and me.
Cold-cap reactions in vitrification of nuclear waste glass: experiments and modeling

International Nuclear Information System (INIS)

Chun, Jaehun; Pierce, David A.; Pokorny, Richard; Hrma, Pavel R.

2013-01-01

Cold-cap reactions are multiple overlapping reactions that occur in the waste-glass melter during the vitrification process when the melter feed is being converted to molten glass. In this study, we used differential scanning calorimetry (DSC) to investigate cold-cap reactions in a high-alumina high-level waste melter feed. To separate the reaction heat from both sensible heat and experimental instability, we employed the run/rerun method, which enabled us to define the degree of conversion based on the reaction heat and to estimate the heat capacity of the reacting feed. Assuming that the reactions are nearly independent and can be approximated by the nth order kinetics, we obtained the kinetic parameters using the Kissinger method combined with least squares analysis. The resulting mathematical simulation of the cold-cap reactions provides a key element for the development of an advanced cold-cap model
Eukaryotic initiation factor 3 (eIF3) and 5’ mRNA leader sequences as agents of translational regulation in Arabidopsis. Final report

Energy Technology Data Exchange (ETDEWEB)

von Arnim, Albrecht G. [Univ. of Tennessee, Knoxville, TN (United States)

2015-02-04

Protein synthesis, or translation, consumes a sizable fraction of the cell’s energy budget, estimated at 5% and up to 50% in differentiated and growing cells, respectively. Plants also invest significant energy and biomass to construct and maintain the translation apparatus. Translation is regulated by a variety of external stimuli. Compared to transcriptional control, attributes of translational control include reduced sensitivity to stochastic fluctuation, a finer gauge of control, and more rapid responsiveness to environmental stimuli. Yet, our murky understanding of translational control allows few generalizations. Consequently, translational regulation is underutilized in the context of transgene regulation, although synthetic biologists are now beginning to appropriate RNA-level gene regulation into their regulatory circuits. We also know little about how translational control contributes to the diversity of plant form and function. This project explored how an emerging regulatory mRNA sequence element, upstream open reading frames (uORFs), is integrated with the general translation initiation machinery to permit translational regulation on specific mRNAs.
Quaternized Chitosan-Capped Mesoporous Silica Nanoparticles as Nanocarriers for Controlled Pesticide Release.

Science.gov (United States)

Cao, Lidong; Zhang, Huirong; Cao, Chong; Zhang, Jiakun; Li, Fengmin; Huang, Qiliang

2016-06-28

Nanotechnology-based pesticide formulations would ensure effective utilization of agricultural inputs. In the present work, mesoporous silica nanoparticles (MSNs) with particle diameters of ~110 nm and pore sizes of ~3.7 nm were synthesized via a liquid crystal templating mechanism. A water-soluble chitosan (CS) derivative ( N -(2-hydroxyl)propyl-3-trimethyl ammonium CS chloride, HTCC) was successfully capped on the surface of pyraclostrobin-loaded MSNs. The physicochemical and structural analyses showed that the electrostatic interactions and hydrogen bonding were the major forces responsible for the formation of HTCC-capped MSNs. HTCC coating greatly improved the loading efficiency (LC) (to 40.3%) compared to using bare MSNs as a single encapsulant (26.7%). The microstructure of the nanoparticles was revealed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The pyraclostrobin-loaded nanoparticles showed an initial burst and subsequent sustained release behavior. HTCC-capped MSNs released faster than bare MSNs in the initial stage. Pyraclostrobin-loaded HTCC-capped MSNs with half doses of pyraclostrobin technical demonstrated almost the same fungicidal activity against Phomopsis asparagi (Sacc.), which obviously reduced the applied pesticide and enhanced the utilization efficiency. Therefore, HTCC-decorated MSNs demonstrated great potential as nanocarriers in agrochemical applications.

The Jigsaw Puzzle of mRNA Translation Initiation in Eukaryotes: A Decade of Structures Unraveling the Mechanics of the Process.

Science.gov (United States)

Hashem, Yaser; Frank, Joachim

2018-03-01

Translation initiation in eukaryotes is a highly regulated and rate-limiting process. It results in the assembly and disassembly of numerous transient and intermediate complexes involving over a dozen eukaryotic initiation factors (eIFs). This process culminates in the accommodation of a start codon marking the beginning of an open reading frame at the appropriate ribosomal site. Although this process has been extensively studied by hundreds of groups for nearly half a century, it has been only recently, especially during the last decade, that we have gained deeper insight into the mechanics of the eukaryotic translation initiation process. This advance in knowledge is due in part to the contributions of structural biology, which have shed light on the molecular mechanics underlying the different functions of various eukaryotic initiation factors. In this review, we focus exclusively on the contribution of structural biology to the understanding of the eukaryotic initiation process, a long-standing jigsaw puzzle that is just starting to yield the bigger picture. Expected final online publication date for the Annual Review of Biophysics Volume 47 is May 20, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Typologically robust statistical machine translation : Understanding and exploiting differences and similarities between languages in machine translation

NARCIS (Netherlands)

Daiber, J.

2018-01-01

Machine translation systems often incorporate modeling assumptions motivated by properties of the language pairs they initially target. When such systems are applied to language families with considerably different properties, translation quality can deteriorate. Phrase-based machine translation
Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS)

NARCIS (Netherlands)

Kuemmerle-Deschner, Jasmin B.; Ozen, Seza; Tyrrell, Pascal N.; Kone-Paut, Isabelle; Goldbach-Mansky, Raphaela; Lachmann, Helen; Blank, Norbert; Hoffman, Hal M.; Weissbarth-Riedel, Elisabeth; Hugle, Boris; Kallinich, Tilmann; Gattorno, Marco; Gul, Ahmet; Ter Haar, Nienke; Oswald, Marlen; Dedeoglu, Fatma; Cantarini, Luca; Benseler, Susanne M.

2017-01-01

Cryopyrin-associated periodic syndrome (CAPS) is a rare, heterogeneous disease entity associated with NLRP3 gene mutations and increased interleukin-1 (IL-1) secretion. Early diagnosis and rapid initiation of IL-1 inhibition prevent organ damage. The aim of the study was to develop and validate
Natural physical and biological processes compromise the long-term performance of compacted soil caps

International Nuclear Information System (INIS)

Smith, E.D.

1995-01-01

Compacted soil barriers are components of essentially all caps placed on closed waste disposal sites. The intended functions of soil barriers in waste facility caps include restricting infiltration of water and release of gases and vapors, either independently or in combination with synthetic membrane barriers, and protecting other manmade or natural barrier components. Review of the performance of installed soil barriers and of natural processes affecting their performance indicates that compacted soil caps may function effectively for relatively short periods (years to decades), but natural physical and biological processes can be expected to cause them to fail in the long term (decades to centuries). This paper addresses natural physical and biological processes that compromise the performance of compacted soil caps and suggests measures that may reduce the adverse consequences of these natural failure mechanisms
Phosphorylation and interactions associated with the control of the Leishmania Poly-A Binding Protein 1 (PABP1) function during translation initiation.

Science.gov (United States)

de Melo Neto, Osvaldo P; da Costa Lima, Tamara D C; Merlo, Kleison C; Romão, Tatiany P; Rocha, Pollyanna O; Assis, Ludmila A; Nascimento, Larissa M; Xavier, Camila C; Rezende, Antonio M; Reis, Christian R S; Papadopoulou, Barbara

2018-03-23

The Poly-A Binding Protein (PABP) is a conserved eukaryotic polypeptide involved in many aspects of mRNA metabolism. During translation initiation, PABP interacts with the translation initiation complex eIF4F and enhances the translation of polyadenylated mRNAs. Schematically, most PABPs can be divided into an N-terminal RNA-binding region, a non-conserved linker segment and the C-terminal MLLE domain. In pathogenic Leishmania protozoans, three PABP homologues have been identified, with the first one (PABP1) targeted by phosphorylation and shown to co-immunoprecipitate with an eIF4F-like complex (EIF4E4/EIF4G3) implicated in translation initiation. Here, PABP1 phosphorylation was shown to be linked to logarithmic cell growth, reminiscent of EIF4E4 phosphorylation, and coincides with polysomal association. Phosphorylation targets multiple serine-proline (SP) or threonine-proline (TP) residues within the PABP1 linker region. This is an essential protein, but phosphorylation is not needed for its association with polysomes or cell viability. Mutations which do impair PABP1 polysomal association and are required for viability do not prevent phosphorylation, although further mutations lead to a presumed inactive protein largely lacking phosphorylated isoforms. Co-immunoprecipitation experiments were carried out to investigate PABP1 function further, identifying several novel protein partners and the EIF4E4/EIF4G3 complex, but no other eIF4F-like complex or subunit. A novel, direct interaction between PABP1 and EIF4E4 was also investigated and found to be mediated by the PABP1 MLLE binding to PABP Interacting Motifs (PAM2) within the EIF4E4 N-terminus. The results shown here are consistent with phosphorylation of PABP1 being part of a novel pathway controlling its function and possibly translation in Leishmania.
Improvements in Pain Outcomes in a Canadian Pediatric Teaching Hospital Following Implementation of a Multifaceted, Knowledge Translation Initiative

Directory of Open Access Journals (Sweden)

Lisa M Zhu

2012-01-01

Full Text Available BACKGROUND: A previous audit performed at a tertiary/quaternary pediatric hospital in Toronto, Ontario, demonstrated suboptimal assessment and treatment of children’s pain. Knowledge translation (KT initiatives (education, reminders, audit and feedback were implemented to address identified care gaps; however, the impact is unknown.
Entrainment to periodic initiation and transition rates in a computational model for gene translation.

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Michael Margaliot

Full Text Available Periodic oscillations play an important role in many biomedical systems. Proper functioning of biological systems that respond to periodic signals requires the ability to synchronize with the periodic excitation. For example, the sleep/wake cycle is a manifestation of an internal timing system that synchronizes to the solar day. In the terminology of systems theory, the biological system must entrain or phase-lock to the periodic excitation. Entrainment is also important in synthetic biology. For example, connecting several artificial biological systems that entrain to a common clock may lead to a well-functioning modular system. The cell-cycle is a periodic program that regulates DNA synthesis and cell division. Recent biological studies suggest that cell-cycle related genes entrain to this periodic program at the gene translation level, leading to periodically-varying protein levels of these genes. The ribosome flow model (RFM is a deterministic model obtained via a mean-field approximation of a stochastic model from statistical physics that has been used to model numerous processes including ribosome flow along the mRNA. Here we analyze the RFM under the assumption that the initiation and/or transition rates vary periodically with a common period T. We show that the ribosome distribution profile in the RFM entrains to this periodic excitation. In particular, the protein synthesis pattern converges to a unique periodic solution with period T. To the best of our knowledge, this is the first proof of entrainment in a mathematical model for translation that encapsulates aspects such as initiation and termination rates, ribosomal movement and interactions, and non-homogeneous elongation speeds along the mRNA. Our results support the conjecture that periodic oscillations in tRNA levels and other factors related to the translation process can induce periodic oscillations in protein levels, and may suggest a new approach for re-engineering genetic
Heat shock-induced accumulation of translation elongation and termination factors precedes assembly of stress granules in S. cerevisiae.

Directory of Open Access Journals (Sweden)

Tomas Grousl

Full Text Available In response to severe environmental stresses eukaryotic cells shut down translation and accumulate components of the translational machinery in stress granules (SGs. Since they contain mainly mRNA, translation initiation factors and 40S ribosomal subunits, they have been referred to as dominant accumulations of stalled translation preinitiation complexes. Here we present evidence that the robust heat shock-induced SGs of S. cerevisiae also contain translation elongation factors eEF3 (Yef3p and eEF1Bγ2 (Tef4p as well as translation termination factors eRF1 (Sup45p and eRF3 (Sup35p. Despite the presence of the yeast prion protein Sup35 in heat shock-induced SGs, we found out that its prion-like domain is not involved in the SGs assembly. Factors eEF3, eEF1Bγ2 and eRF1 were accumulated and co-localized with Dcp2 foci even upon a milder heat shock at 42°C independently of P-bodies scaffolding proteins. We also show that eEF3 accumulations at 42°C determine sites of the genuine SGs assembly at 46°C. We suggest that identification of translation elongation and termination factors in SGs might help to understand the mechanism of the eIF2α factor phosphorylation-independent repression of translation and SGs assembly.
Synthesis of organically-capped metallic zinc nanoparticles using electrical explosion of wires (EEW) coupled with PIERMEN

Energy Technology Data Exchange (ETDEWEB)

Abdelkader, Elseddik M.; Jelliss, Paul A., E-mail: jellissp@slu.edu; Buckner, Steven W., E-mail: buckners@slu.edu

2015-01-15

In this study zinc nanoparticles (ZNPs) were produced using electrical explosion of wires (EEW) with NP size around 100 nm. The explosion chamber was constructed from Teflon to withstand the shockwave, to allow growth and reaction of the incipient ZNPs in various organic solvents, and to allow a constant flow of argon creating an inert atmosphere. We utilized polymerization initiation by electron-rich metallic nanoparticles (PIERMEN) as the capping technique for the reactive ZNPs. Epoxides and alkenes served as the capping monomers. Epoxide caps underwent oligomerization on the surface of the NPs to form a protective polyether cap which renders the particles stable, non-pyrophoric in air, and dispersible in organic solvents. We investigated various Zn to monomer molar ratios varying from 1:1 to 10:1. Polyethylene glycol was also used as a capping agent and was found to give the smallest average Zn core sizes with the metal core diameters varying from 15 to 20 nm. Several solvents were used to study differences in resultant particle size and we observe toluene to give the smallest metal cores. Transmission electron microscopy shows the spherical particles with the metallic core embedded in a polymer matrix. The sample consists of predominantly smaller particles, but there was also a broad size distribution giving a range of 20–150 nm. Powder X-ray diffraction (PXRD) was used to confirm the identity of the metallic NPs. The capping agents were characterized using both attenuated total reflectance-Fourier transform infra-red (ATR-FTIR) and Raman spectroscopies. There was no evidence for formation of zinc oxide with appropriate organic capping agents and solvent combinations; thus, this is the first report of production of pure metallic zinc nanoparticles with an organic cap using EEW. - Highlights: • Organically-capped Zn metal nanoparticles are produced by EEW in organic solution. • Incipient Zn metal nanoparticles initiate oligomerization of epoxide and
Evaluation Of The Physical Stability, Ground Water Seepage Control, And Faunal Changes Associated With An AquaBlok® Sediment Cap

Science.gov (United States)

Active sediment caps are being considered for addressing contaminated sediment areas in surface-water bodies. A demonstration of an active cap designed to reduce advective transport of contaminants using AquaBlok® (active cap material) was initiated in a small study a...
A nanobody targeting the F-actin capping protein CapG restrains breast cancer metastasis.

Science.gov (United States)

Van Impe, Katrien; Bethuyne, Jonas; Cool, Steven; Impens, Francis; Ruano-Gallego, David; De Wever, Olivier; Vanloo, Berlinda; Van Troys, Marleen; Lambein, Kathleen; Boucherie, Ciska; Martens, Evelien; Zwaenepoel, Olivier; Hassanzadeh-Ghassabeh, Gholamreza; Vandekerckhove, Joël; Gevaert, Kris; Fernández, Luis Ángel; Sanders, Niek N; Gettemans, Jan

2013-12-13

Aberrant turnover of the actin cytoskeleton is intimately associated with cancer cell migration and invasion. Frequently however, evidence is circumstantial, and a reliable assessment of the therapeutic significance of a gene product is offset by lack of inhibitors that target biologic properties of a protein, as most conventional drugs do, instead of the corresponding gene. Proteomic studies have demonstrated overexpression of CapG, a constituent of the actin cytoskeleton, in breast cancer. Indirect evidence suggests that CapG is involved in tumor cell dissemination and metastasis. In this study, we used llama-derived CapG single-domain antibodies or nanobodies in a breast cancer metastasis model to address whether inhibition of CapG activity holds therapeutic merit. We raised single-domain antibodies (nanobodies) against human CapG and used these as intrabodies (immunomodulation) after lentiviral transduction of breast cancer cells. Functional characterization of nanobodies was performed to identify which biochemical properties of CapG are perturbed. Orthotopic and tail vein in vivo models of metastasis in nude mice were used to assess cancer cell spreading. With G-actin and F-actin binding assays, we identified a CapG nanobody that binds with nanomolar affinity to the first CapG domain. Consequently, CapG interaction with actin monomers or actin filaments is blocked. Intracellular delocalization experiments demonstrated that the nanobody interacts with CapG in the cytoplasmic environment. Expression of the nanobody in breast cancer cells restrained cell migration and Matrigel invasion. Notably, the nanobody prevented formation of lung metastatic lesions in orthotopic xenograft and tail-vein models of metastasis in immunodeficient mice. We showed that CapG nanobodies can be delivered into cancer cells by using bacteria harboring a type III protein secretion system (T3SS). CapG inhibition strongly reduces breast cancer metastasis. A nanobody-based approach offers
Quaternized Chitosan-Capped Mesoporous Silica Nanoparticles as Nanocarriers for Controlled Pesticide Release

Directory of Open Access Journals (Sweden)

Lidong Cao

2016-06-01

Full Text Available Nanotechnology-based pesticide formulations would ensure effective utilization of agricultural inputs. In the present work, mesoporous silica nanoparticles (MSNs with particle diameters of ~110 nm and pore sizes of ~3.7 nm were synthesized via a liquid crystal templating mechanism. A water-soluble chitosan (CS derivative (N-(2-hydroxylpropyl-3-trimethyl ammonium CS chloride, HTCC was successfully capped on the surface of pyraclostrobin-loaded MSNs. The physicochemical and structural analyses showed that the electrostatic interactions and hydrogen bonding were the major forces responsible for the formation of HTCC-capped MSNs. HTCC coating greatly improved the loading efficiency (LC (to 40.3% compared to using bare MSNs as a single encapsulant (26.7%. The microstructure of the nanoparticles was revealed by scanning electron microscopy (SEM and transmission electron microscopy (TEM. The pyraclostrobin-loaded nanoparticles showed an initial burst and subsequent sustained release behavior. HTCC-capped MSNs released faster than bare MSNs in the initial stage. Pyraclostrobin-loaded HTCC-capped MSNs with half doses of pyraclostrobin technical demonstrated almost the same fungicidal activity against Phomopsis asparagi (Sacc., which obviously reduced the applied pesticide and enhanced the utilization efficiency. Therefore, HTCC-decorated MSNs demonstrated great potential as nanocarriers in agrochemical applications.
Potyviral VPg enhances viral RNA Translation and inhibits reporter mRNA translation in planta.

Science.gov (United States)

Eskelin, Katri; Hafrén, Anders; Rantalainen, Kimmo I; Mäkinen, Kristiina

2011-09-01

Viral protein genome-linked (VPg) plays a central role in several stages of potyvirus infection. This study sought to answer questions about the role of Potato virus A (PVA; genus Potyvirus) VPg in viral and host RNA expression. When expressed in Nicotiana benthamiana leaves in trans, a dual role of VPg in translation is observed. It repressed the expression of monocistronic luciferase (luc) mRNA and simultaneously induced a significant upregulation in the expression of both replicating and nonreplicating PVA RNAs. This enhanced viral gene expression was due at least to the 5' untranslated region (UTR) of PVA RNA, eukaryotic initiation factors 4E and iso 4E [eIF4E/eIF(iso)4E], and the presence of a sufficient amount of VPg. Coexpression of VPg with viral RNA increased the viral RNA amount, which was not the case with the monocistronic mRNA. Both mutations at certain lysine residues in PVA VPg and eIF4E/eIF(iso)4E depletion reduced its ability to upregulate the viral RNA expression. These modifications were also involved in VPg-mediated downregulation of monocistronic luc expression. These results suggest that VPg can titrate eIF4Es from capped monocistronic RNAs. Because VPg-mediated enhancement of viral gene expression required eIF4Es, it is possible that VPg directs eIF4Es to promote viral RNA expression. From this study it is evident that VPg can serve as a specific regulator of PVA expression by boosting the viral RNA amounts as well as the accumulation of viral translation products. Such a mechanism could function to protect viral RNA from being degraded and to secure efficient production of coat protein (CP) for virion formation.
Potyviral VPg Enhances Viral RNA Translation and Inhibits Reporter mRNA Translation In Planta▿

Science.gov (United States)

Eskelin, Katri; Hafrén, Anders; Rantalainen, Kimmo I.; Mäkinen, Kristiina

2011-01-01

Viral protein genome-linked (VPg) plays a central role in several stages of potyvirus infection. This study sought to answer questions about the role of Potato virus A (PVA; genus Potyvirus) VPg in viral and host RNA expression. When expressed in Nicotiana benthamiana leaves in trans, a dual role of VPg in translation is observed. It repressed the expression of monocistronic luciferase (luc) mRNA and simultaneously induced a significant upregulation in the expression of both replicating and nonreplicating PVA RNAs. This enhanced viral gene expression was due at least to the 5′ untranslated region (UTR) of PVA RNA, eukaryotic initiation factors 4E and iso 4E [eIF4E/eIF(iso)4E], and the presence of a sufficient amount of VPg. Coexpression of VPg with viral RNA increased the viral RNA amount, which was not the case with the monocistronic mRNA. Both mutations at certain lysine residues in PVA VPg and eIF4E/eIF(iso)4E depletion reduced its ability to upregulate the viral RNA expression. These modifications were also involved in VPg-mediated downregulation of monocistronic luc expression. These results suggest that VPg can titrate eIF4Es from capped monocistronic RNAs. Because VPg-mediated enhancement of viral gene expression required eIF4Es, it is possible that VPg directs eIF4Es to promote viral RNA expression. From this study it is evident that VPg can serve as a specific regulator of PVA expression by boosting the viral RNA amounts as well as the accumulation of viral translation products. Such a mechanism could function to protect viral RNA from being degraded and to secure efficient production of coat protein (CP) for virion formation. PMID:21697470
/sup 58,60,62/Ni (. cap alpha. ,p) three--nucleon transfer reactions and. cap alpha. optical potential ambiguities

Energy Technology Data Exchange (ETDEWEB)

Yuanda, Wang; Xiuming, Bao; Zhiqiang, Mao; Rongfang, Yuan; Keling, Wen; Binyin, Huang; Zhifu, Wang; Shuming, Li; Jianan, Wang; Zuxun, Sun; others, and

1985-11-01

The differential cross sections are measured using 26.0 MeV ..cap alpha.. particle for /sup 58,62/Ni(..cap alpha.., ..cap alpha..) /sup 58,62/Ni and /sup 58,62/Ni(..cap alpha..,p) /sup 61,65/Cu reactions as well as 25.4 MeV ..cap alpha.. particle for /sup 60/Ni(..cap alpha.., ..cap alpha..)/sup 69/Ni and /sup 60/Ni(..cap alpha.., p)/sup 63/Cu reactions. Consistent calculations with optical model and ZR DWBA are made for (..cap alpha.., ..cap alpha..) and (..cap alpha.., p) reactions by using of single, two, three and four nucleon optical potential parameters. For elastic scattering due to the ..cap alpha.. optical potential ambiguities, all the above optical potential can reproduce the experimental angular distributions. However, the single, two and three nucleon potential, including the Baird's mass systematics and the Chang's energy systematics of ..cap alpha.. potentials, obviously can not provide a reasonable fitting with the (..cap alpha..,p) reaction experimental data. Only the results from the four nucleon potential is in good agreement with the (..cap alpha..,p) reaction experimental data. This reveals that in the ..cap alpha..-particle induced transfer reactions, the real depth of the ..cap alpha..-nucleus optical potential should be rather deep.
How does the antagonism between capping and anti-capping proteins affect actin network dynamics?

International Nuclear Information System (INIS)

Hu Longhua; Papoian, Garegin A

2011-01-01

Actin-based cell motility is essential to many biological processes. We built a simplified, three-dimensional computational model and subsequently performed stochastic simulations to study the growth dynamics of lamellipodia-like branched networks. In this work, we shed light on the antagonism between capping and anti-capping proteins in regulating actin dynamics in the filamentous network. We discuss detailed mechanisms by which capping and anti-capping proteins affect the protrusion speed of the actin network and the rate of nucleation of filaments. We computed a phase diagram showing the regimes of motility enhancement and inhibition by these proteins. Our work shows that the effects of capping and anti-capping proteins are mainly transmitted by modulation of the filamentous network density and local availability of monomeric actin. We discovered that the combination of the capping/anti-capping regulatory network with nucleation-promoting proteins introduces robustness and redundancy in cell motility machinery, allowing the cell to easily achieve maximal protrusion speeds under a broader set of conditions. Finally, we discuss distributions of filament lengths under various conditions and speculate on their potential implication for the emergence of filopodia from the lamellipodial network.
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.
A free vein graft cap influences neuroma formation after nerve transection.

Science.gov (United States)

Galeano, Mariarosaria; Manasseri, Benedetto; Risitano, Giovanni; Geuna, Stefano; Di Scipio, Federica; La Rosa, Paola; Delia, Gabriele; D'Alcontres, Francesco Stagno; Colonna, Michele R

2009-01-01

: Neuroma formation is a major problem in nerve surgery and consensus about its prevention has not been reached. It has been suggested that vein covering can reduce neuroma formation in transected nerves. In this article, the Authors propose an easy and novel method of covering by nerve stump capping with a free vein graft. : Neuroma-like lesions were created on the rat thigh sectioning the femoral nerve above its division in 16 animals. The proximal nerve stump was invaginated into the lumen of a 1.5 cm long femoral free vein graft on the right side, and the vein was closed on itself by microsurgical sutures to form a cap for the nerve stump. On the left side acting as the control neuroma, the nerve was cut and left uncovered. Histological and immunohistochemical assessment was used to quantify the degree of neuroma formation. : Significant differences were found in both neuroma size and axon-glia organization between the treated and control sides indicating that free vein graft capping reduced neuroma formation in comparison to uncovered nerve stumps. : Our results confirm that vein-covering of a transected nerve stump can be effective in reducing neuroma formation. Moreover, unlike previous works that buried the nerve into an adjacent vein left in place, our experiments showed that also the use of a free vein graft cap can hinder neuroma formation. Although translation of rat experiments to the clinics should be dealt with caution, our data suggest a careful clinical use of the technique. (c) 2009 Wiley-Liss, Inc. Microsurgery, 2009.
Dual Nature of Translational Control by Regulatory BC RNAs ▿

Science.gov (United States)

Eom, Taesun; Berardi, Valerio; Zhong, Jun; Risuleo, Gianfranco; Tiedge, Henri

2011-01-01

In higher eukaryotes, increasing evidence suggests, gene expression is to a large degree controlled by RNA. Regulatory RNAs have been implicated in the management of neuronal function and plasticity in mammalian brains. However, much of the molecular-mechanistic framework that enables neuronal regulatory RNAs to control gene expression remains poorly understood. Here, we establish molecular mechanisms that underlie the regulatory capacity of neuronal BC RNAs in the translational control of gene expression. We report that regulatory BC RNAs employ a two-pronged approach in translational control. One of two distinct repression mechanisms is mediated by C-loop motifs in BC RNA 3′ stem-loop domains. These C-loops bind to eIF4B and prevent the factor's interaction with 18S rRNA of the small ribosomal subunit. In the second mechanism, the central A-rich domains of BC RNAs target eIF4A, specifically inhibiting its RNA helicase activity. Thus, BC RNAs repress translation initiation in a bimodal mechanistic approach. As BC RNA functionality has evolved independently in rodent and primate lineages, our data suggest that BC RNA translational control was necessitated and implemented during mammalian phylogenetic development of complex neural systems. PMID:21930783
Pharmacogenetic diversification by alternative translation initiation: background channels to the fore.

Science.gov (United States)

Abbott, G W

2014-02-15

Unanticipated complexity of drug-target interactions creates a headache for those attempting to rationalize and create simple models of antiarrhythmic action, but can also introduce opportunities for increased drug specificity, or for potentially advantageous spatial and temporal variation in drug effects. The newest findings reported by Kisselbach et al. in this issue are a case in point. Building upon previous pioneering work demonstrating that neuronal K 2P 2.1 potassium-selective "background" channels can become permeable to sodium ions depending upon alternative translation initiation (ATI) (Thomas et al., 2008), the Thomas lab now shows that ATI of K 2P 2.1 and K 2P 10.1, which are also expressed in the heart, can cause a fivefold shift in sensitivity to block by the β-receptor (and potassium channel) antagonist, carvedilol (Kisselbach et al., 2014). This article is protected by copyright. All rights reserved.

Recommendations for translation and reliability testing of International Spinal Cord Injury Data Sets.

Science.gov (United States)

Biering-Sørensen, F; Alexander, M S; Burns, S; Charlifue, S; DeVivo, M; Dietz, V; Krassioukov, A; Marino, R; Noonan, V; Post, M W M; Stripling, T; Vogel, L; Wing, P

2011-03-01

To provide recommendations regarding translation and reliability testing of International Spinal Cord Injury (SCI) Data Sets. The Executive Committee for the International SCI Standards and Data Sets. Translations of any specific International SCI Data Set can be accomplished by translation from the English version into the target language, and be followed by a back-translation into English, to confirm that the original meaning has been preserved. Another approach is to have the initial translation performed by translators who have knowledge of SCI, and afterwards controlled by other person(s) with the same kind of knowledge. The translation process includes both language translation and cultural adaptation, and therefore shall not be made word for word, but will strive to include conceptual equivalence. At a minimum, the inter-rater reliability should be tested by no less than two independent observers, and preferably in multiple countries. Translations must include information on the name, role and background of everyone involved in the translation process, and shall be dated and noted with a version number. By following the proposed guidelines, translated data sets should assure comparability of data acquisition across countries and cultures. If the translation process identifies irregularities or misrepresentation in either the original English version or the target language, the working group for the particular International SCI Data Set shall revise the data set accordingly, which may include re-wording of the original English version in order to accomplish a compromise in the content of the data set.
47 CFR 54.623 - Cap.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Cap. 54.623 Section 54.623 Telecommunication... Universal Service Support for Health Care Providers § 54.623 Cap. (a) Amount of the annual cap. The annual cap on federal universal service support for health care providers shall be $400 million per funding...
47 CFR 54.507 - Cap.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Cap. 54.507 Section 54.507 Telecommunication... Universal Service Support for Schools and Libraries § 54.507 Cap. (a) Amount of the annual cap. The annual funding cap on federal universal service support for schools and libraries shall be $2.25 billion per...
Dynamic Interaction between Cap & Trade and Electricity Markets

Science.gov (United States)

Jeev, Kumar

Greenhouse Gases (GHG), such as Carbon-Dioxide (CO2), which is released in the atmosphere due to anthropogenic activities like power production, are now accepted as the main culprits for global warming. The Regional Greenhouse Gas Initiative (RGGI), an initiative of the North East and Mid-Atlantic States of the United States (US) for limiting the emission of GHG, has developed a regional cap-and-trade program for CO2 emissions for power plants. Existing cap-and-trade programs in US and Europe for Greenhouse Gases have recently been plagued by over-allocation. Carbon prices recently collapsed in all these markets during the global recession. Since then, there have been significant policy changes, which have resulted in the adoption of aggressive emission cap targets by most major carbon emission markets. This is expected to make carbon emissions availability more restrictive, raising the prices of these credits. These emissions markets are expected to have a major impact on the wholesale electricity markets. Two models to study the interaction of these two markets are presented. These models assess the impact of the emissions market on wholesale electricity prices. The first model characterizes the competition between two types of power plants (coal and gas) in both the electricity and emissions markets as a dynamic game using the Cournot approximation. Under this approximation, we find that in the Nash equilibrium the plants increase their permit allocation to high-demand periods and the marginal value of each credit for a plant is identical in all periods under their optimal equilibrium strategy. The second numerical model allows us to explicitly evaluate the closed loop equilibrium of the dynamic interaction of two competitors in these markets. We find that plants often try to corner the market and push prices all the way to the price cap. Power plants derive most of their profits from these extreme price regimes. In the experiments where trading is allowed
The regulation of protein synthesis and translation factors by CD3 and CD28 in human primary T lymphocytes

Directory of Open Access Journals (Sweden)

Proud Christopher G

2002-05-01

Full Text Available Abstract Background Activation of human resting T lymphocytes results in an immediate increase in protein synthesis. The increase in protein synthesis after 16–24 h has been linked to the increased protein levels of translation initiation factors. However, the regulation of protein synthesis during the early onset of T cell activation has not been studied in great detail. We studied the regulation of protein synthesis after 1 h of activation using αCD3 antibody to stimulate the T cell receptor and αCD28 antibody to provide the co-stimulus. Results Activation of the T cells with both antibodies led to a sustained increase in the rate of protein synthesis. The activities and/or phosphorylation states of several translation factors were studied during the first hour of stimulation with αCD3 and αCD28 to explore the mechanism underlying the activation of protein synthesis. The initial increase in protein synthesis was accompanied by activation of the guanine nucleotide exchange factor, eukaryotic initiation factor (eIF 2B, and of p70 S6 kinase and by dephosphorylation of eukaryotic elongation factor (eEF 2. Similar signal transduction pathways, as assessed using signal transduction inhibitors, are involved in the regulation of protein synthesis, eIF2B activity and p70 S6 kinase activity. A new finding was that the p38 MAPK α/β pathway was involved in the regulation of overall protein synthesis in primary T cells. Unexpectedly, no changes were detected in the phosphorylation state of the cap-binding protein eIF4E and the eIF4E-binding protein 4E-BP1, or the formation of the cap-binding complex eIF4F. Conclusions Both eIF2B and p70 S6 kinase play important roles in the regulation of protein synthesis during the early onset of T cell activation.
Expression of the Eukaryotic Translation Initiation Factors 4E and 2α in Non-Hodgkin’s Lymphomas

Science.gov (United States)

Wang, Songtao; Rosenwald, Igor B.; Hutzler, Michael J.; Pihan, German A.; Savas, Lou; Chen, Jane-Jane; Woda, Bruce A.

1999-01-01

Transition of cells from quiescence to proliferation requires an increase in the rate of protein synthesis, which is regulated in part by two key translation initiation factors, 4E and 2α. The expression and activity of both factors are increased transiently when normal resting cells are stimulated to proliferate. They are constitutively elevated in oncogene transformed cultured cells, and overexpression of either initiation factor in rodent cells makes them tumorigenic. In this study we investigate an association between the expression of translation initiation factors and lymphomagenesis. We have analyzed the expression of the protein synthesis initiation factors 4E and 2α by immunohistochemistry in reactive lymph nodes and several types of non-Hodgkin’s lymphoma representing a wide range of clinical behaviors based on the Revised European-American Lymphoma behavioral classification. The study included 7 benign lymph nodes with follicular hyperplasia, 26 indolent lymphomas (6 marginal zone lymphomas, 7 small lymphocytic lymphomas, and 13 follicular lymphomas, grades 1 and 2), 16 moderately aggressive lymphomas (8 mantle cell lymphomas and 8 follicular lymphomas, grade 3), 24 aggressive lymphomas (14 large-B-cell lymphomas and 10 anaplastic large-cell lymphomas), and 15 highly aggressive lymphomas (7 lymphoblastic lymphomas and 8 Burkitt’s lymphomas). Strong expression of initiation factors 4E and 2α was demonstrated in the germinal centers of reactive follicles. Minimal or no expression was seen in the mantle zones and surrounding paracortices, indicating that high expression of initiation factors 4E and 2α is associated with the active proliferation of lymphocytes. Most cases of aggressive and highly aggressive lymphomas showed strong expression of initiation factors 4E and 2α, in contrast to the cases of indolent and moderately aggressive lymphoma, in which their expression was intermediate between the germinal centers and the mantles of reactive
Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

International Nuclear Information System (INIS)

Simonetti, Angelita; Marzi, Stefano; Fabbretti, Attilio; Hazemann, Isabelle; Jenner, Lasse; Urzhumtsev, Alexandre; Gualerzi, Claudio O.; Klaholz, Bruno P.

2013-01-01

The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2 is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue
Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

Energy Technology Data Exchange (ETDEWEB)

Simonetti, Angelita [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Marzi, Stefano [Architecture et Réactivité de l’ARN, UPR 9002 CNRS, IBMC (Institute of Molecular and Cellular Biology), 15 Rue R. Descartes, 67084 Strasbourg, France, Université de Strasbourg, 67000 Strasbourg (France); Fabbretti, Attilio [University of Camerino, 62032 Camerino (Monaco) (Italy); Hazemann, Isabelle; Jenner, Lasse [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale -INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Urzhumtsev, Alexandre [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Université de Lorraine, 54506 Vandoeuvre-lès-Nancy (France); Gualerzi, Claudio O. [University of Camerino, 62032 Camerino (Monaco) (Italy); Klaholz, Bruno P., E-mail: klaholz@igbmc.fr [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France)

2013-06-01

The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2 is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue.
Depletion of eIF4G from yeast cells narrows the range of translational efficiencies genome-wide

Directory of Open Access Journals (Sweden)

Hinnebusch Alan G

2011-01-01

Full Text Available Abstract Background Eukaryotic translation initiation factor 4G (eIF4G is thought to influence the translational efficiencies of cellular mRNAs by its roles in forming an eIF4F-mRNA-PABP mRNP that is competent for attachment of the 43S preinitiation complex, and in scanning through structured 5' UTR sequences. We have tested this hypothesis by determining the effects of genetically depleting eIF4G from yeast cells on global translational efficiencies (TEs, using gene expression microarrays to measure the abundance of mRNA in polysomes relative to total mRNA for ~5900 genes. Results Although depletion of eIF4G is lethal and reduces protein synthesis by ~75%, it had small effects (less than a factor of 1.5 on the relative TE of most genes. Within these limits, however, depleting eIF4G narrowed the range of translational efficiencies genome-wide, with mRNAs of better than average TE being translated relatively worse, and mRNAs with lower than average TE being translated relatively better. Surprisingly, the fraction of mRNAs most dependent on eIF4G display an average 5' UTR length at or below the mean for all yeast genes. Conclusions This finding suggests that eIF4G is more critical for ribosome attachment to mRNAs than for scanning long, structured 5' UTRs. Our results also indicate that eIF4G, and the closed-loop mRNP it assembles with the m7 G cap- and poly(A-binding factors (eIF4E and PABP, is not essential for translation of most (if not all mRNAs but enhances the differentiation of translational efficiencies genome-wide.
The human Ago2 MC region does not contain an eIF4E-like mRNA cap binding motif

Directory of Open Access Journals (Sweden)

Grishin Nick V

2009-01-01

Full Text Available Abstract Background Argonaute (Ago proteins interact with small regulatory RNAs to mediate gene regulatory pathways. A recent report by Kiriakidou et al. 1 describes an MC sequence region identified in Ago2 that displays similarity to the cap-binding motif in translation initiation factor 4E (eIF4E. In a cap-bound eIF4E structure, two important aromatic residues of the motif stack on either side of a 7-methylguanosine 5'-triphosphate (m7Gppp base. The corresponding Ago2 aromatic residues (F450 and F505 were hypothesized to perform the same cap-binding function. However, the detected similarity between the MC sequence and the eIF4E cap-binding motif was questionable. Results A number of sequence-based and structure-based bioinformatics methods reveal the reported similarity between the Ago2 MC sequence region and the eIF4E cap-binding motif to be spurious. Alternatively, the MC sequence region is confidently assigned to the N-terminus of the Ago piwi module, within the mid domain of experimentally determined prokaryotic Ago structures. Confident mapping of the Ago2 MC sequence region to the piwi mid domain results in a homology-based structure model that positions the identified aromatic residues over 20 Å apart, with one of the aromatic side chains (F450 contributing instead to the hydrophobic core of the domain. Conclusion Correct functional prediction based on weak sequence similarity requires substantial evolutionary and structural support. The evolutionary context of the Ago mid domain suggested by multiple sequence alignment is limited to a conserved hydrophobicity profile required for the fold and a motif following the MC region that binds guide RNA. Mapping of the MC sequence to the mid domain structure reveals Ago2 aromatics that are incompatible with eIF4E-like mRNA cap-binding, yet display some limited local structure similarities that cause the chance sequence match to eIF4E. Reviewers This article was reviewed by Arcady Mushegian
Evidence of Parallel Processing During Translation

DEFF Research Database (Denmark)

Balling, Laura Winther; Hvelplund, Kristian Tangsgaard; Sjørup, Annette Camilla

2014-01-01

conclude that translation is a parallel process and that literal translation is likely to be a universal initial default strategy in translation. This conclusion is strengthened by the fact that all three experiments were relatively naturalistic, due to the combination of remote eye tracking and mixed...
An upstream open reading frame modulates ebola virus polymerase translation and virus replication.

Directory of Open Access Journals (Sweden)

Reed S Shabman

2013-01-01

Full Text Available Ebolaviruses, highly lethal zoonotic pathogens, possess longer genomes than most other non-segmented negative-strand RNA viruses due in part to long 5' and 3' untranslated regions (UTRs present in the seven viral transcriptional units. To date, specific functions have not been assigned to these UTRs. With reporter assays, we demonstrated that the Zaire ebolavirus (EBOV 5'-UTRs lack internal ribosomal entry site function. However, the 5'-UTRs do differentially regulate cap-dependent translation when placed upstream of a GFP reporter gene. Most dramatically, the 5'-UTR derived from the viral polymerase (L mRNA strongly suppressed translation of GFP compared to a β-actin 5'-UTR. The L 5'-UTR is one of four viral genes to possess upstream AUGs (uAUGs, and ablation of each uAUG enhanced translation of the primary ORF (pORF, most dramatically in the case of the L 5'-UTR. The L uAUG was sufficient to initiate translation, is surrounded by a "weak" Kozak sequence and suppressed pORF translation in a position-dependent manner. Under conditions where eIF2α was phosphorylated, the presence of the uORF maintained translation of the L pORF, indicating that the uORF modulates L translation in response to cellular stress. To directly address the role of the L uAUG in virus replication, a recombinant EBOV was generated in which the L uAUG was mutated to UCG. Strikingly, mutating two nucleotides outside of previously-defined protein coding and cis-acting regulatory sequences attenuated virus growth to titers 10-100-fold lower than a wild-type virus in Vero and A549 cells. The mutant virus also exhibited decreased viral RNA synthesis as early as 6 hours post-infection and enhanced sensitivity to the stress inducer thapsigargin. Cumulatively, these data identify novel mechanisms by which EBOV regulates its polymerase expression, demonstrate their relevance to virus replication and identify a potential therapeutic target.
Polar Ice Caps: a Canary for the Greenland Ice Sheet

Science.gov (United States)

Honsaker, W.; Lowell, T. V.; Sagredo, E.; Kelly, M. A.; Hall, B. L.

2010-12-01

Ice caps are glacier masses that are highly sensitive to climate change. Because of their hypsometry they can have a binary state. When relatively slight changes in the equilibrium line altitude (ELA) either intersect or rise above the land the ice can become established or disappear. Thus these upland ice masses have a fast response time. Here we consider a way to extract the ELA signal from independent ice caps adjacent to the Greenland Ice Sheet margin. It may be that these ice caps are sensitive trackers of climate change that also impact the ice sheet margin. One example is the Istorvet Ice Cap located in Liverpool Land, East Greenland (70.881°N, 22.156°W). The ice cap topography and the underlying bedrock surface dips to the north, with peak elevation of the current ice ranging in elevation from 1050 to 745 m.a.s.l. On the eastern side of the ice mass the outlet glaciers extending down to sea level. The western margin has several small lobes in topographic depressions, with the margin reaching down to 300 m.a.s.l. Topographic highs separate the ice cap into at least 5 main catchments, each having a pair of outlet lobes toward either side of the ice cap. Because of the regional bedrock slope each catchment has its own elevation range. Therefore, as the ELA changes it is possible for some catchments of the ice cap to experience positive mass balance while others have a negative balance. Based on weather observations we estimate the present day ELA to be ~1000 m.a.s.l, meaning mass balance is negative for the majority of the ice cap. By tracking glacier presence/absence in these different catchments, we can reconstruct small changes in the ELA. Another example is the High Ice Cap (informal name) in Milne Land (70.903°N, 25.626°W, 1080 m), East Greenland. Here at least 4 unconformities in ice layers found near the southern margin of the ice cap record changing intervals of accumulation and ablation. Therefore, this location may also be sensitive to slight
The case for indexed price caps for U.S. electric utilities

International Nuclear Information System (INIS)

Lowry, M.N.

1991-01-01

Indexed price caps are a promising alternative to traditional, cost-of-service utility rate regulation. In just a decade, they have sprung from the drawing boards of economists to use by major utilities in a number of industries. Several authors have discussed the merits of indexed price caps for U.S. electric utilities. Despite their efforts, many parties to electric utility policy making are unfamiliar with the subject. This is unsurprising given the policy controversies that already embroil the industry. It is also unfortunate, since indexed price caps may help solve some of the problems that prompt these controversies. Indexed price caps can improve electric utility rate regulation in two ways. Utilities would have strong incentives to improve performance without the micromanagement that increasingly characterizes state-level regulation. Utilities could also be granted more extensive marketing freedoms, since indexes can protect customers from cross-subsidization. Two areas of concern about indexed price cap plans have emerged in recent discussions that the author has held with officials of electric utilities, intervenor groups, and regulatory agencies. Officials are often unclear on plan details, and therefore may not appreciate the degree of flexibility that is possible in plan design. Confusion over the available options in price cap adjustment indexes and the logic behind them is especially widespread. Officials also desire a clearer expression of how indexed price caps can coexist with current regulatory initiatives. This article details the major attributes of index plans, provides a brief history of indexing, discusses index design options in depth, and concludes with a vision of how indexed price caps can be made operational in today's electric utility industry
Translation Factors Specify Cellular Metabolic State

Directory of Open Access Journals (Sweden)

Juan Mata

2016-08-01

Full Text Available In this issue of Cell Reports, Shah et al. present evidence that a subcomplex of the eIF3 translation initiation factor regulates translation of mRNAs encoding components of the mitochondrial electron transport chain and glycolytic enzymes, thus linking translational control with energy metabolism.
Mo/Si multilayers with enhanced TiO II- and RuO II-capping layers

Science.gov (United States)

Yulin, Sergiy; Benoit, Nicolas; Feigl, Torsten; Kaiser, Norbert; Fang, Ming; Chandhok, Manish

2008-03-01

The lifetime of Mo/Si multilayer-coated projection optics is one of the outstanding issues on the road of commercialization of extreme-ultraviolet lithography (EUVL). The application of Mo/Si multilayer optics in EUVL requires both sufficient radiation stability and also the highest possible normal-incidence reflectivity. A serious problem of conventional high-reflective Mo/Si multilayers capped by silicon is the considerable degradation of reflective properties due to carbonization and oxidation of the silicon surface layer under exposure by EUV radiation. In this study, we focus on titanium dioxide (TiO II) and ruthenium dioxide (RuO II) as promising capping layer materials for EUVL multilayer coatings. The multilayer designs as well as the deposition parameters of the Mo/Si systems with different capping layers were optimized in terms of maximum peak reflectivity at the wavelength of 13.5 nm and longterm stability under high-intensive irradiation. Optimized TiO II-capped Mo/Si multilayer mirrors with an initial reflectivity of 67.0% presented a reflectivity drop of 0.6% after an irradiation dose of 760 J/mm2. The reflectivity drop was explained by the partial oxidation of the silicon sub-layer. No reflectivity loss after similar irradiation dose was found for RuO II-capped Mo/Si multilayer mirrors having initial peak reflectivity of 66%. In this paper we present data on improved reflectivity of interface-engineered TiO II- and RuO II-capped Mo/Si multilayer mirrors due to the minimization of both interdiffusion processes inside the multilayer stack and absorption loss in the oxide layer. Reflectivities of 68.5% at the wavelength of 13.4 nm were achieved for both TiO II- and RuO II-capped Mo/Si multilayer mirrors.
The rebirth of the cervical cap.

Science.gov (United States)

Cappiello, J D; Grainger-Harrison, M

1981-01-01

In an effort to dispel myths surrounding the cervical cap, the historical and political factors affecting the cap's use in the U.S. are described. Clinical aspects of cap fitting are also included. The cervical cap has found only limited acceptance in the U.S. Skepticisms on the part of physicians may be the result of 2 factors: confusion of the cervical cap with intracervical devices used for artificial insemination and confusion with stem pessaries; and the lack of clinical research and statistical evaluation of efficacy rates. The latter factor prompted Tietze et al. to conduct the only U.S. statistical study of the cap in 1953. Of the 143 women studied, the pregnancy rate was 7.6/100 years of use. Of the 28 unplanned pregnancies, 6 were related to faulty technique or omission of a spermicide and 10 were instances of admittedly irregular use. When these failures are omitted, the theoretical effectiveness rate is about 98%. Some practitioners are concerned about an increased incidence of cervical erosion with cap use. Possibly currently conducted studies will show that cap and spermicide users have a lower incidence of cervical erosion than women using no contraceptive method. Study findings suggest that the cervical cap may afford protection without any spermicidal supplement, but the use of spermicides continues to be recommended to clients. Advantages of the cervical cap include the following: it can be left in place longer than a diaphragm without additional applications of spermicide in the vagina; and the insertion of the cap is unrelated to the time of intercourse. Despite research on toleration of the cap for 3 weeks at a time, it is recommended that the cap be worn for only a few days at a time. At this time there are no manufacturers of cervical caps for contraceptive use in the U.S. The cap is now being imported from England and it costs $6.00. A factor that has made the cap unpopular with many physicians is the lengthy time required for fitting. An
Effects of x-ray irradiation on the induction of. cap alpha. -amylase synthesis by gibberelic acid in the aleurone system of barley

Energy Technology Data Exchange (ETDEWEB)

Zellner, H

1974-01-01

The influence of ionizing radiation on a system without DNA replication and cell division was investigated with the aid of GA/sub 3/-induced ..cap alpha..-amylase synthesis in aleurone cells of barley. The reaction of the system was determined by dose effect curves (after irradiation of one half of the endosperms in rest) for the synthesis and secretion of ..cap alpha..-amylase, protein, and reducing sugars. The system proves to be highly radiation-resistant. The course of the synthesis of ..cap alpha..-amylase after X-ray irradiation with varying doses during enzyme synthesis suggests that transcription occurs in the middle of the lag-phase and is the most sensitive stage in enzyme synthesis, while translation alone is less sensitive to radiation.
Site-specific multipoint fluorescence measurement system with end-capped optical fibers.

Science.gov (United States)

Song, Woosub; Moon, Sucbei; Lee, Byoung-Cheol; Park, Chul-Seung; Kim, Dug Young; Kwon, Hyuk Sang

2011-07-10

We present the development and implementation of a spatially and spectrally resolved multipoint fluorescence correlation spectroscopy (FCS) system utilizing multiple end-capped optical fibers and an inexpensive laser source. Specially prepared end-capped optical fibers placed in an image plane were used to both collect fluorescence signals from the sample and to deliver signals to the detectors. The placement of independently selected optical fibers on the image plane was done by monitoring the end-capped fiber tips at the focus using a CCD, and fluorescence from specific positions of a sample were collected by an end-capped fiber, which could accurately represent light intensities or spectral data without incurring any disturbance. A fast multipoint spectroscopy system with a time resolution of ∼1.5 ms was then implemented using a prism and an electron multiplying charge coupled device with a pixel binning for the region of interest. The accuracy of our proposed system was subsequently confirmed by experimental results, based on an FCS analysis of microspheres in distilled water. We expect that the proposed multipoint site-specific fluorescence measurement system can be used as an inexpensive fluorescence measurement tool to study many intracellular and molecular dynamics in cell biology. © 2011 Optical Society of America
Microtubule's conformational cap

DEFF Research Database (Denmark)

Flyvbjerg, H.

1999-01-01

The molecular mechanisms that allow elongation of the unstable microtubule lattice remain unclear. It is usually thought that the GDP-liganded tubulin lattice is capped by a small layer of GTP- or GDP-P(i)-liganded molecules, the so called "GTP-cap". Here, we point-out that the elastic properties...

A semi-analytical method to estimate the effective slip length of spreading spherical-cap shaped droplets using Cox theory

Science.gov (United States)

Wörner, M.; Cai, X.; Alla, H.; Yue, P.

2018-03-01

The Cox–Voinov law on dynamic spreading relates the difference between the cubic values of the apparent contact angle (θ) and the equilibrium contact angle to the instantaneous contact line speed (U). Comparing spreading results with this hydrodynamic wetting theory requires accurate data of θ and U during the entire process. We consider the case when gravitational forces are negligible, so that the shape of the spreading drop can be closely approximated by a spherical cap. Using geometrical dependencies, we transform the general Cox law in a semi-analytical relation for the temporal evolution of the spreading radius. Evaluating this relation numerically shows that the spreading curve becomes independent from the gas viscosity when the latter is less than about 1% of the drop viscosity. Since inertia may invalidate the made assumptions in the initial stage of spreading, a quantitative criterion for the time when the spherical-cap assumption is reasonable is derived utilizing phase-field simulations on the spreading of partially wetting droplets. The developed theory allows us to compare experimental/computational spreading curves for spherical-cap shaped droplets with Cox theory without the need for instantaneous data of θ and U. Furthermore, the fitting of Cox theory enables us to estimate the effective slip length. This is potentially useful for establishing relationships between slip length and parameters in numerical methods for moving contact lines.
Computed tomography on a defective CANDU fuel pencil end cap

International Nuclear Information System (INIS)

Lupton, L.R.

1985-09-01

Five tomographic slices through a defective end cap from a CANDU fuel pencil have been generated using a Co-60 source and a first generation translate-rotate tomography scanner. An anomaly in the density distribution that is believed to have resulted from the defect has been observed. However, with the 0.30 mm spatial resolution used, it has not been possible to state unequivocally whether the change in density is caused by a defect in the weld or a statistical anomaly in the data. It is concluded that a microtomography system, with a spatial resolution in the range of 0.1 mm, could detect the flaw
Eukaryotic translation initiation factor 2B-beta (eIF2Bβ), a new class of plant virus resistance gene.

Science.gov (United States)

Shopan, Jannat; Mou, Haipeng; Zhang, Lili; Zhang, Changtong; Ma, Weiwei; Walsh, John A; Hu, Zhongyuan; Yang, Jinghua; Zhang, Mingfang

2017-06-01

Recessive resistances to plant viruses in the Potyvirus genus have been found to be based on mutations in the plant eukaryotic translation initiation factors, eIF4E and eIF4G or their isoforms. Here we report that natural, monogenic recessive resistance to the Potyvirus Turnip mosaic virus (TuMV) has been found in a number of mustard (Brassica juncea) accessions. Bulked segregant analysis and sequencing of resistant and susceptible plant lines indicated the resistance is controlled by a single recessive gene, recessive TuMV resistance 03 (retr03), an allele of the eukaryotic translation initiation factor 2B-beta (eIF2Bβ). Silencing of eIF2Bβ in a TuMV-susceptible mustard plant line and expression of eIF2Bβ from a TuMV-susceptible line in a TuMV-resistant mustard plant line confirmed the new resistance mechanism. A functional copy of a specific allele of eIF2Bβ is required for efficient TuMV infection. eIF2Bβ represents a new class of virus resistance gene conferring resistance to any pathogen. eIF2B acts as a guanine nucleotide exchange factor (GEF) for its GTP-binding protein partner eIF2 via interaction with eIF2·GTP at an early step in translation initiation. Further genotyping indicated that a single non-synonymous substitution (A120G) in the N-terminal region of eIF2Bβ was responsible for the TuMV resistance. A reproducible marker has been developed, facilitating marker-assisted selection for TuMV resistance in B. juncea. Our findings provide a new target for seeking natural resistance to potyviruses and new opportunities for the control of potyviruses using genome editing techniques targeted on eIF2Bβ. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.
75 FR 49527 - Caps Visual Communications, LLC; Black Dot Group; Formerly Known as Caps Group Acquisition, LLC...

Science.gov (United States)

2010-08-13

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-74,195] Caps Visual Communications, LLC; Black Dot Group; Formerly Known as Caps Group Acquisition, LLC Chicago, IL; Amended... of Caps Visual Communications, LLC, Black Dot Group, formerly known as Caps Group Acquisition, LLC...
Core competencies in the science and practice of knowledge translation: description of a Canadian strategic training initiative.

Science.gov (United States)

Straus, Sharon E; Brouwers, Melissa; Johnson, David; Lavis, John N; Légaré, France; Majumdar, Sumit R; McKibbon, K Ann; Sales, Anne E; Stacey, Dawn; Klein, Gail; Grimshaw, Jeremy

2011-12-09

Globally, healthcare systems are attempting to optimize quality of care. This challenge has resulted in the development of implementation science or knowledge translation (KT) and the resulting need to build capacity in both the science and practice of KT. We are attempting to meet these challenges through the creation of a national training initiative in KT. We have identified core competencies in this field and have developed a series of educational courses and materials for three training streams. We report the outline for this approach and the progress to date. We have prepared a strategy to develop, implement, and evaluate a national training initiative to build capacity in the science and practice of KT. Ultimately through this initiative, we hope to meet the capacity demand for KT researchers and practitioners in Canada that will lead to improved care and a strengthened healthcare system.
Macrophage Capping Protein CapG Is a Putative Oncogene Involved in Migration and Invasiveness in Ovarian Carcinoma

Directory of Open Access Journals (Sweden)

J. Glaser

2014-01-01

Full Text Available The actin binding protein CapG modulates cell motility by interacting with the cytoskeleton. CapG is associated with tumor progression in different nongynecologic tumor entities and overexpression in breast cancer cell lines correlates with a more invasive phenotype in vitro. Here, we report a significant CapG overexpression in 18/47 (38% of ovarian carcinomas (OC analyzed by qRealTime-PCR analyses. Functional analyses in OC cell lines through siRNA mediated CapG knockdown and CapG overexpression showed CapG-dependent cell migration and invasiveness. A single nucleotide polymorphism rs6886 inside the CapG gene was identified, affecting a CapG phosphorylation site and thus potentially modifying CapG function. The minor allele frequency (MAF of SNP rs6886 (c.1004A/G was higher and the homozygous (A/A, His335 genotype was significantly more prevalent in patients with fallopian tube carcinomas (50% as in controls (10%. With OC being one of the most lethal cancer diseases, the detection of novel biomarkers such as CapG could reveal new diagnostic and therapeutic targets. Moreover, in-depth analyses of SNP rs6886 related to FTC and OC will contribute to a better understanding of carcinogenesis and progression of OC.
The thermospheric effects of a rapid polar cap expansion

Directory of Open Access Journals (Sweden)

D. W. Idenden

Full Text Available In a previous publication we used results from a coupled thermosphere-ionosphere-plasmasphere model to illustrate a new mechanism for the formation of a large-scale patch of ionisation arising from a rapid polar cap expansion. Here we describe the thermospheric response to that polar cap expansion, and to the ionospheric structure produced. The response is dominated by the energy and momentum input at the dayside throat during the expansion phase itself. These inputs give rise to a large-scale travelling atmospheric disturbance (TAD that propagates both antisunward across the polar cap and equatorward at speeds much greater than both the ion drifts and the neutral winds. We concentrate only on the initially poleward travelling disturbance. The disturbance is manifested in the neutral temperature and wind fields, the height of the pressure level surfaces and in the neutral density at fixed heights. The thermospheric effects caused by the ionospheric structure produced during the expansion are hard to discern due to the dominating effects of the TAD.

Key words. Ionosphere (ionosphere · atmosphere interaction; modeling and forecasting; plasma convection.
The human papillomavirus type 16 E6 oncoprotein activates mTORC1 signaling and increases protein synthesis.

Science.gov (United States)

Spangle, Jennifer M; Münger, Karl

2010-09-01

The mammalian target of rapamycin (mTOR) kinase acts as a cellular rheostat that integrates signals from a variety of cellular signal transduction pathways that sense growth factor and nutrient availability as well as intracellular energy status. It was previously reported that the human papillomavirus type 16 (HPV16) E6 oncoprotein may activate the S6 protein kinase (S6K) through binding and E6AP-mediated degradation of the mTOR inhibitor tuberous sclerosis complex 2 (TSC2) (Z. Lu, X. Hu, Y. Li, L. Zheng, Y. Zhou, H. Jiang, T. Ning, Z. Basang, C. Zhang, and Y. Ke, J. Biol. Chem. 279:35664-35670, 2004; L. Zheng, H. Ding, Z. Lu, Y. Li, Y. Pan, T. Ning, and Y. Ke, Genes Cells 13:285-294, 2008). Our results confirmed that HPV16 E6 expression causes an increase in mTORC1 activity through enhanced phosphorylation of mTOR and activation of downstream signaling pathways S6K and eukaryotic initiation factor binding protein 1 (4E-BP1). However, we did not detect a decrease in TSC2 levels in HPV16 E6-expressing cells. We discovered, however, that HPV16 E6 expression causes AKT activation through the upstream kinases PDK1 and mTORC2 under conditions of nutrient deprivation. We show that HPV16 E6 expression causes an increase in protein synthesis by enhancing translation initiation complex assembly at the 5' mRNA cap and an increase in cap-dependent translation. The increase in cap-dependent translation likely results from HPV16 E6-induced AKT/mTORC1 activation, as the assembly of the translation initiation complex and cap-dependent translation are rapamycin sensitive. Lastly, coexpression of the HPV16 E6 and E7 oncoproteins does not affect HPV16 E6-induced activation of mTORC1 and cap-dependent translation. HPV16 E6-mediated activation of mTORC1 signaling and cap-dependent translation may be a mechanism to promote viral replication under conditions of limited nutrient supply in differentiated, HPV oncoprotein-expressing proliferating cells.
Eddy intrusion of hot plasma into the polar cap and formation of polar-cap arcs

International Nuclear Information System (INIS)

Chiu, Y.T.; Gorney, D.J.

1983-01-01

We present plasma and electric field data obtained by the S3-3 satellite over the polar caps. We demonstrate that: (1) plasma signatures in the polar cap arc formation region near 5000 km altitude show clear intrusions of plasma sheet (approx.keV) and magneto sheath (approx.100 eV) plasma into a background of low-energy polar cap plasma; (2) the combined plasma and electric field signatures (electron inverted-V, ion beam and delxE<0) are exactly the same as in the evening discrete arc. We interpret this equivalence of polar cap and evening discrete arc signatures as indication that their formation processes are identical. The spatial structures of polar cap electric fields and the associated plasma signatures are consistent with the hypothesis that plasma intrusion into the polar cap takes the form of multiple cellular eddies. This hypothesis provides a unifying view of arc formation and arc configurations
North Polar Cap

Science.gov (United States)

2004-01-01

[figure removed for brevity, see original site] This week we will be looking at five examples of laminar wind flow on the north polar cap. On Earth, gravity-driven south polar cap winds are termed 'catabatic' winds. Catabatic winds begin over the smooth expanse of the cap interior due to temperature differences between the atmosphere and the surface. Once begun, the winds sweep outward along the surface of the polar cap toward the sea. As the polar surface slopes down toward sealevel, the wind speeds increase. Catabatic wind speeds in the Antartic can reach several hundreds of miles per hour. In the images of the Martian north polar cap we can see these same type of winds. Notice the streamers of dust moving downslope over the darker trough sides, these streamers show the laminar flow regime coming off the cap. Within the trough we see turbulent clouds of dust, kicked up at the trough base as the winds slow down and enter a chaotic flow regime. The horizontal lines in these images are due to framelet overlap and lighting conditions over the bright polar cap. Image information: VIS instrument. Latitude 86.5, Longitude 64.5 East (295.5 West). 40 meter/pixel resolution. Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time. NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen
The structure of hookworm platelet inhibitor (HPI), a CAP superfamily member from Ancylostoma caninum.

Science.gov (United States)

Ma, Dongying; Francischetti, Ivo M B; Ribeiro, Jose M C; Andersen, John F

2015-06-01

Secreted protein components of hookworm species include a number of representatives of the cysteine-rich/antigen 5/pathogenesis-related 1 (CAP) protein family known as Ancylostoma-secreted proteins (ASPs). Some of these have been considered as candidate antigens for the development of vaccines against hookworms. The functions of most CAP superfamily members are poorly understood, but one form, the hookworm platelet inhibitor (HPI), has been isolated as a putative antagonist of the platelet integrins αIIbβ3 and α2β1. Here, the crystal structure of HPI is described and its structural features are examined in relation to its possible function. The HPI structure is similar to those of other ASPs and shows incomplete conservation of the sequence motifs CAP1 and CAP2 that are considered to be diagnostic of CAP superfamily members. The asymmetric unit of the HPI crystal contains a dimer with an extensive interaction interface, but chromatographic measurements indicate that it is primarily monomeric in solution. In the dimeric structure, the putative active-site cleft areas from both monomers are united into a single negatively charged depression. A potential Lys-Gly-Asp disintegrin-like motif was identified in the sequence of HPI, but is not positioned at the apex of a tight turn, making it unlikely that it interacts with the integrin. Recombinant HPI produced in Escherichia coli was found not to inhibit the adhesion of human platelets to collagen or fibrinogen, despite having a native structure as shown by X-ray diffraction. This result corroborates previous analyses of recombinant HPI and suggests that it might require post-translational modification or have a different biological function.
The alignment system of the ATLAS muon end-cap spectrometer

International Nuclear Information System (INIS)

Schricker, A.

2002-08-01

to the analytic shape model that allows to interpolate between the discrete number of measured points to describe any other bar shape. Expressing these changes with virtual loads that account for all forces acting on the bar, finally leads to the required precision. The basic principles are explained and detailed design and test results are presented. As part of the process one octant, the smallest independent unit of the end-cap alignment system, has been erected in the H8 test beam area to evaluate the systems performance of the proposed alignment strategy. Measurements are presently carried out with this prototype setup and initial results will be presented. Finally, work done during the development of the alignment bars led to a proposal for the final ATLAS alignment bars and to a manual describing the process from assembling until installation. (author)
Primary structure of the. cap alpha. -subunit of Na/sup +/, K/sup +/-ATPase. II. Isolation, reverse transcription, and cloning of messenger RNA

Energy Technology Data Exchange (ETDEWEB)

Petrukhin, K.E.; Broude, N.E.; Arsenyan, S.G.; Grishin, A.V.; Dzhandzhugazyan, K.N.; Modyanov, N.N.

1986-10-01

The messenger RNA coding the ..cap alpha..-subunit of Na/sup +/,K/sup +/-ATPase has been isolated from the outer medullary layer of porcine kidneys. The mRNA gives a specific hybridization band in the 25S-26S region with three oligonucleotide probes synthesized on the basis of information on the structure of three peptides isolated from a tryptic hydrolyzate of the ..cap alpha..-subunit of Na/sup +/,K/sup +/-ATPase. The translation of the mRNA in Xenopus laevis oocytes followed by immunochemical identification of the products of synthesis confirmed the presence of the mRNA of the ..cap alpha..-subunit of Na/sup +/,K/sup +/-ATPase in an enriched fraction of poly(A/sup +/)-RNA. This preparation has been used for the synthesis of cloning of double-stranded cDNA.
Designing Smart Charter School Caps

Science.gov (United States)

Dillon, Erin

2010-01-01

In 2007, Andrew J. Rotherham proposed a new approach to the contentious issue of charter school caps, the statutory limits on charter school growth in place in several states. Rotherham's proposal, termed "smart charter school caps," called for quality sensitive caps that allow the expansion of high-performing charter schools while also…
Impact of Vial Capping on Residual Seal Force and Container Closure Integrity.

Science.gov (United States)

Mathaes, Roman; Mahler, Hanns-Christian; Roggo, Yves; Ovadia, Robert; Lam, Philippe; Stauch, Oliver; Vogt, Martin; Roehl, Holger; Huwyler, Joerg; Mohl, Silke; Streubel, Alexander

2016-01-01

computed tomography-to characterize different container closure system combinations that had been sealed using different capping process parameter settings. The residual seal force tester can analyze a variety of different container closure systems independent of the capping equipment. An adequate and safe residual seal force range for each container closure system configuration can be established with the residual seal force tester and additional methods like computed tomography scans and leak testing. In the residual seal force range studied, the physical container closure integrity of the container closure system was warranted. © PDA, Inc. 2016.
Coordinate independent expression for transverse trace-free tensors

International Nuclear Information System (INIS)

Conboye, Rory

2016-01-01

The transverse and trace-free (TT) part of the extrinsic curvature represents half of the dynamical degrees of freedom of the gravitational field in the 3 + 1 formalism. As such, it is part of the freely specifiable initial data for numerical relativity. Though TT tensors in three-space possess only two component degrees of freedom, they cannot ordinarily be given solely by two scalar potentials. Such expressions have been derived, however, in coordinate form, for all TT tensors in flat space which are also translationally or axially symmetric (Conboye and Murchadha 2014 Class. Quantum Grav. 31 085019). Since TT tensors are conformally covariant, these also give TT tensors in conformally flat space. In this article, the work above has been extended by giving a coordinate-independent expression for these TT tensors. The translational and axial symmetry conditions have also been generalized to invariance along any hypersurface orthogonal Killing vector. (paper)
Denoising of chaotic signal using independent component analysis and empirical mode decomposition with circulate translating

Science.gov (United States)

Wen-Bo, Wang; Xiao-Dong, Zhang; Yuchan, Chang; Xiang-Li, Wang; Zhao, Wang; Xi, Chen; Lei, Zheng

2016-01-01

In this paper, a new method to reduce noises within chaotic signals based on ICA (independent component analysis) and EMD (empirical mode decomposition) is proposed. The basic idea is decomposing chaotic signals and constructing multidimensional input vectors, firstly, on the base of EMD and its translation invariance. Secondly, it makes the independent component analysis on the input vectors, which means that a self adapting denoising is carried out for the intrinsic mode functions (IMFs) of chaotic signals. Finally, all IMFs compose the new denoised chaotic signal. Experiments on the Lorenz chaotic signal composed of different Gaussian noises and the monthly observed chaotic sequence on sunspots were put into practice. The results proved that the method proposed in this paper is effective in denoising of chaotic signals. Moreover, it can correct the center point in the phase space effectively, which makes it approach the real track of the chaotic attractor. Project supported by the National Science and Technology, China (Grant No. 2012BAJ15B04), the National Natural Science Foundation of China (Grant Nos. 41071270 and 61473213), the Natural Science Foundation of Hubei Province, China (Grant No. 2015CFB424), the State Key Laboratory Foundation of Satellite Ocean Environment Dynamics, China (Grant No. SOED1405), the Hubei Provincial Key Laboratory Foundation of Metallurgical Industry Process System Science, China (Grant No. Z201303), and the Hubei Key Laboratory Foundation of Transportation Internet of Things, Wuhan University of Technology, China (Grant No.2015III015-B02).
NATURE MANAGEMENT, LANDSCAPE AND THE CAP

OpenAIRE

Brouwer, Floor M.; Godeschalk, Frans E.

2004-01-01

The integration of nature management, landscape and environmental concerns into the Common Agricultural Policy (CAP) has gained momentum with the CAP reforms adopted in June 2003. The report explores instruments and approaches that contribute to the inte-gration of nature conservation and landscape concerns into the CAP. A broader use of the CAP instruments might help to achieve nature types in the Netherlands.
Core competencies in the science and practice of knowledge translation: description of a Canadian strategic training initiative

Directory of Open Access Journals (Sweden)

Straus Sharon E

2011-12-01

Full Text Available Abstract Background Globally, healthcare systems are attempting to optimize quality of care. This challenge has resulted in the development of implementation science or knowledge translation (KT and the resulting need to build capacity in both the science and practice of KT. Findings We are attempting to meet these challenges through the creation of a national training initiative in KT. We have identified core competencies in this field and have developed a series of educational courses and materials for three training streams. We report the outline for this approach and the progress to date. Conclusions We have prepared a strategy to develop, implement, and evaluate a national training initiative to build capacity in the science and practice of KT. Ultimately through this initiative, we hope to meet the capacity demand for KT researchers and practitioners in Canada that will lead to improved care and a strengthened healthcare system.
Dissociation of eIF4E-binding protein 2 (4E-BP2 from eIF4E independent of Thr37/Thr46 phosphorylation in the ischemic stress response.

Directory of Open Access Journals (Sweden)

María I Ayuso

Full Text Available Eukaryotic initiation factor (eIF 4E-binding proteins (4E-BPs are translational repressors that bind specifically to eIF4E and are critical in the control of protein translation. 4E-BP2 is the predominant 4E-BP expressed in the brain, but their role is not well known. Here, we characterized four forms of 4E-BP2 detected by two-dimensional gel electrophoresis (2-DGE in brain. The form with highest electrophoretic mobility was the main form susceptible to phosphorylation at Thr37/Thr46 sites, phosphorylation that was detected in acidic spots. Cerebral ischemia and subsequent reperfusion induced dephosphorylation and phosphorylation of 4E-BP2 at Thr37/Thr46, respectively. The induced phosphorylation was in parallel with the release of 4E-BP2 from eIF4E, although two of the phosphorylated 4E-BP2 forms were bound to eIF4E. Upon long-term reperfusion, there was a decrease in the binding of 4E-BP2 to eIF4E in cerebral cortex, demonstrated by cap binding assays and 4E-BP2-immunoprecipitation experiments. The release of 4E-BP2 from eIF4E was without changes in 4E-BP2 phosphorylation or other post-translational modification recognized by 2-DGE. These findings demonstrated specific changes in 4E-BP2/eIF4E association dependent and independent of 4E-BP2 phosphorylation. The last result supports the notion that phosphorylation may not be the uniquely regulation for the binding of 4E-BP2 to eIF4E under ischemic stress.

CAPS Simulation Environment Development

Science.gov (United States)

Murphy, Douglas G.; Hoffman, James A.

2005-01-01

The final design for an effective Comet/Asteroid Protection System (CAPS) will likely come after a number of competing designs have been simulated and evaluated. Because of the large number of design parameters involved in a system capable of detecting an object, accurately determining its orbit, and diverting the impact threat, a comprehensive simulation environment will be an extremely valuable tool for the CAPS designers. A successful simulation/design tool will aid the user in identifying the critical parameters in the system and eventually allow for automatic optimization of the design once the relationships of the key parameters are understood. A CAPS configuration will consist of space-based detectors whose purpose is to scan the celestial sphere in search of objects likely to make a close approach to Earth and to determine with the greatest possible accuracy the orbits of those objects. Other components of a CAPS configuration may include systems for modifying the orbits of approaching objects, either for the purpose of preventing a collision or for positioning the object into an orbit where it can be studied or used as a mineral resource. The Synergistic Engineering Environment (SEE) is a space-systems design, evaluation, and visualization software tool being leveraged to simulate these aspects of the CAPS study. The long-term goal of the SEE is to provide capabilities to allow the user to build and compare various CAPS designs by running end-to-end simulations that encompass the scanning phase, the orbit determination phase, and the orbit modification phase of a given scenario. Herein, a brief description of the expected simulation phases is provided, the current status and available features of the SEE software system is reported, and examples are shown of how the system is used to build and evaluate a CAPS detection design. Conclusions and the roadmap for future development of the SEE are also presented.
The cervical cap (image)

Science.gov (United States)

The cervical cap is a flexible rubber cup-like device that is filled with spermicide and self-inserted over the cervix ... left in place several hours after intercourse. The cap is a prescribed device fitted by a health ...
Does uncertainty justify intensity emission caps?

International Nuclear Information System (INIS)

Quirion, Philippe

2005-01-01

Environmental policies often set 'relative' or 'intensity' emission caps, i.e. emission limits proportional to the polluting firm's output. One of the arguments put forth in favour of relative caps is based on the uncertainty on business-as-usual output: if the firm's production level is higher than expected, so will be business-as-usual emissions, hence reaching a given level of emissions will be more costly than expected. As a consequence, it is argued, a higher emission level should be allowed if the production level is more important than expected. We assess this argument with a stochastic analytical model featuring two random variables: the business-as-usual emission level, proportional to output, and the slope of the marginal abatement cost curve. We compare the relative cap to an absolute cap and to a price instrument, in terms of welfare impact. It turns out that in most plausible cases, either a price instrument or an absolute cap yields a higher expected welfare than a relative cap. Quantitatively, the difference in expected welfare is typically very small between the absolute and the relative cap but may be significant between the relative cap and the price instrument. (author)
Cryopyrin-Associated Autoinflammatory Syndromes (CAPS) - Juvenile

Science.gov (United States)

... all ethnic groups can be affected. What are CAPS? Cryopyrin-associated autoinflammatory syndromes (CAPS) consist of three ... ears by magnetic resonance imaging (MRI). How is CAPS treated? Medications that target interleukin-1 are very ...
Changes in root cap pH are required for the gravity response of the Arabidopsis root

Science.gov (United States)

Fasano, J. M.; Swanson, S. J.; Blancaflor, E. B.; Dowd, P. E.; Kao, T. H.; Gilroy, S.

2001-01-01

Although the columella cells of the root cap have been identified as the site of gravity perception, the cellular events that mediate gravity signaling remain poorly understood. To determine if cytoplasmic and/or wall pH mediates the initial stages of root gravitropism, we combined a novel cell wall pH sensor (a cellulose binding domain peptide-Oregon green conjugate) and a cytoplasmic pH sensor (plants expressing pH-sensitive green fluorescent protein) to monitor pH dynamics throughout the graviresponding Arabidopsis root. The root cap apoplast acidified from pH 5.5 to 4.5 within 2 min of gravistimulation. Concomitantly, cytoplasmic pH increased in columella cells from 7.2 to 7.6 but was unchanged elsewhere in the root. These changes in cap pH preceded detectable tropic growth or growth-related pH changes in the elongation zone cell wall by 10 min. Altering the gravity-related columella cytoplasmic pH shift with caged protons delayed the gravitropic response. Together, these results suggest that alterations in root cap pH likely are involved in the initial events that mediate root gravity perception or signal transduction.
Eukaryotic translation initiation factor 3 subunit e controls intracellular calcium homeostasis by regulation of cav1.2 surface expression.

Directory of Open Access Journals (Sweden)

Pawel Buda

Full Text Available Inappropriate surface expression of voltage-gated Ca(2+channels (CaV in pancreatic ß-cells may contribute to the development of type 2 diabetes. First, failure to increase intracellular Ca(2+ concentrations at the sites of exocytosis impedes insulin release. Furthermore, excessive Ca(2+ influx may trigger cytotoxic effects. The regulation of surface expression of CaV channels in the pancreatic β-cells remains unknown. Here, we used real-time 3D confocal and TIRFM imaging, immunocytochemistry, cellular fractionation, immunoprecipitation and electrophysiology to study trafficking of L-type CaV1.2 channels upon β-cell stimulation. We found decreased surface expression of CaV1.2 and a corresponding reduction in L-type whole-cell Ca(2+ currents in insulin-secreting INS-1 832/13 cells upon protracted (15-30 min stimulation. This internalization occurs by clathrin-dependent endocytosis and could be prevented by microtubule or dynamin inhibitors. eIF3e (Eukaryotic translation initiation factor 3 subunit E is part of the protein translation initiation complex, but its effect on translation are modest and effects in ion channel trafficking have been suggested. The factor interacted with CaV1.2 and regulated CaV1.2 traffic bidirectionally. eIF3e silencing impaired CaV1.2 internalization, which resulted in an increased intracellular Ca(2+ load upon stimulation. These findings provide a mechanism for regulation of L-type CaV channel surface expression with consequences for β-cell calcium homeostasis, which will affect pancreatic β-cell function and insulin production.
Translation and cultural adaptation of the Brief Michigan Hand Questionnaire to Brazilian Portuguese language.

Science.gov (United States)

Fernandes, Carlos Henrique; Neto, Jorge Raduan; Meirelles, Lia Miyamoto; Pereira, Carina Nascimento Mastrocinque; Dos Santos, João Baptista Gomes; Faloppa, Flavio

2014-09-01

The use of patient-reported outcome questionnaires is recommended in orthopedic studies. However, validated tools are necessary to ensure the comparability of results across different studies, centers, and countries. The Brief Michigan Hand Questionnaire (BMHQ) can be used for outcome measures in self-evaluation after carpal tunnel release. This study aimed to translate the BMHQ to Portuguese to permit cross-cultural adaptation to Brazilians patients. We translated the Brief Michigan Hand Questionnaire from the original version (English) to Brazilian Portuguese. The translation and cultural adaptation of the content of this tool consisted of six stages, according to the methodology proposed by medical literature: (1) initial translation of the questionnaire by two independent translators; (2) synthesis of translations and reconciliation; (3) back-translation to English of the reconciled version; (4) verification of the cultural equivalence process by an expert committee; (5) pre-testing in a sample of patients to verify understanding of the items; and (6) development of a final version of the BMHQ. The pre-final version of the tool was applied to 43 patients to verify its understanding. Pre-testing showed that the questions and options were satisfactorily understood. The number of items from the original English version was maintained in the Brazilian Portuguese version of BMHQ. The Brazilian Portuguese version of the BMHQ is easily understood by patients and will be useful to clinicians and researchers.
Evaluating U.S. States climate change initiatives

International Nuclear Information System (INIS)

Silva, P.

2004-01-01

This paper evaluates sub-federal efforts to mitigate climate change in the United States through a range of climate-relevant initiatives, identifying principal trends and detailing climate-relevant initiatives in several states. These strategies include renewable electricity mandates, State and regional greenhouse gas emissions inventories, mandatory greenhouse gas emissions reporting, State greenhouse gas emissions caps, greenhouse gas emissions reductions from motor vehicles, and greenhouse gas emissions cap-and-trade programs for electric generation in several States. Many municipalities in the United States are also pursuing a range of climate-relevant initiatives, those actions are beyond the scope of this paper, but it should be noted they also influence state and national consideration of climate-relevant initiatives in the United States. (author)
Evaluating U.S. States climate change initiatives

Energy Technology Data Exchange (ETDEWEB)

Silva, P

2004-07-01

This paper evaluates sub-federal efforts to mitigate climate change in the United States through a range of climate-relevant initiatives, identifying principal trends and detailing climate-relevant initiatives in several states. These strategies include renewable electricity mandates, State and regional greenhouse gas emissions inventories, mandatory greenhouse gas emissions reporting, State greenhouse gas emissions caps, greenhouse gas emissions reductions from motor vehicles, and greenhouse gas emissions cap-and-trade programs for electric generation in several States. Many municipalities in the United States are also pursuing a range of climate-relevant initiatives, those actions are beyond the scope of this paper, but it should be noted they also influence state and national consideration of climate-relevant initiatives in the United States. (author)
The Continuing Challenges of Translational Research: Clinician-Scientists’ Perspective

Directory of Open Access Journals (Sweden)

Shervanthi Homer-Vanniasinkam

2012-01-01

Full Text Available Over the last twenty years, revolutionary advances in biomedicine including gene therapy, stem cell research, proteomics, genomics and nanotechnology have highlighted the progressive need to restructure traditional approaches to basic and clinical research in order to facilitate the rapid, efficient integration and translation of these new technologies into novel effective therapeutics. Over the past ten years, funding bodies in the USA and UK such as the National Institutes of Health (NIH and the Medical Research Council (MRC have been driving translational research by defining and tackling the hurdles but more still remains to be achieved. This article discusses the ongoing challenges translational researchers face and outlines recent initiatives to tackle these including the new changes to translational funding schemes proposed by the NIH and the MRC and the launch of the “European Advanced Translational Research InfraStructure in Medicine” (EATRIS. It is anticipated that initiatives such as these will not only strengthen translational biomedical research programmes already initiated but should lead to rapid benefits to patients and society.
The North Zealand CAP Monitor

DEFF Research Database (Denmark)

Nielsen, Minna; Ravn, Pernille; Notander Clausen, Lise

with CAP. We started with 34 audit variables. Through repeated cycles of testing, feedback and discussions, we reduced the number of indicators to 22 and time per audit from 20 to 10 minutes. Strategy for change To link the monitoring system with our patient pathway for CAP we established an improvement...... Designing a database Designing and testing a dashboard to present indicators in a balanced way Messages for others Auditing patients with a common disease as CAP is useful to identify areas for improvement for a large group of patients. The baseline audit can serve as a basis for a monitoring system......Contect We describe how we developed a monitoring system for community acquired pneumonia (CAP) at North Zealand Regional hospital. We serve 310.000 inhabitants and annually around 3200 patients with CAP are admitted. As part of a program of clinical pathways for common conditions, a pathway...
Systematic identification of non-coding RNA 2,2,7-trimethylguanosine cap structures in Caenorhabditis elegans

Directory of Open Access Journals (Sweden)

Skogerbø Geir

2007-09-01

Full Text Available Abstract Background The 2,2,7-trimethylguanosine (TMG cap structure is an important functional characteristic of ncRNAs with critical cellular roles, such as some snRNAs. Here we used immunoprecipitation with both K121 and R1131 anti-TMG antibodies to systematically identify the TMG cap structures for all presently characterized ncRNAs in C. elegans. Results The two anti-TMG antibodies precipitated a similar group of the C. elegans ncRNAs. All snRNAs known to have a TMG cap structure were found in the precipitate, indicating that our identification system was efficient. Other ncRNA families related to splicing, such as SL RNAs and Sm Y RNAs, were also found in the precipitate, as were 7 C/D box snoRNAs. Further analysis showed that the SL RNAs and the Sm Y RNAs shared a very similar Sm binding site element (AAU4–5GGA, which sequence composition differed somewhat from those of other U snRNAs. There were also 16 ncRNAs without an Sm binding site element in the precipitate, suggesting that for these ncRNAs, TMG formation may occur independently of Sm proteins. Conclusion Our results showed that most ncRNAs predicted to be transcribed by RNA polymerase II had a TMG cap, while those predicted to be transcribed by RNA plymerase III or located in introns did not have a TMG cap structure. Compared to ncRNAs without a TMG cap, TMG-capped ncRNAs tended to have higher expression levels. Five functionally non-annotated ncRNAs also have a TMG cap structure, which might be helpful for identifying the cellular roles of these ncRNAs.
Design and Formative Evaluation of the Policy Liaison Initiative: A Long-Term Knowledge Translation Strategy to Encourage and Support the Use of Cochrane Systematic Reviews for Informing

Science.gov (United States)

Brennan, Sue E.; Cumpston, Miranda; Misso, Marie L.; McDonald, Steve; Murphy, Matthew J.; Green, Sally E.

2016-01-01

The Policy Liaison Initiative (PLI) is a long-term knowledge translation initiative designed to support the use of Cochrane systematic reviews in health policy. A joint initiative between the Australasian Cochrane Centre and Australian Government Department of Health and Ageing, the PLI includes: 1) a community of practice for evidence-informed…
Estimated release from the saltstone landfill effect of landfill caps and landfill-cap/monolith-liner combinations

International Nuclear Information System (INIS)

Wilhite, E.L.

1985-01-01

The effect of capping the entire saltstone landfill is dependent on the effectiveness of the clay cap in preventing infiltration. A cap that is 99% effective will reduce releases from the saltstone landfill by a factor of 7.7. Several combinations of landfill design alterations will result in meeting ground water standards
IMF B(y) and day-night conductivity effects in the expanding polar cap convection model

Science.gov (United States)

Moses, J. J.; Gorney, D. J.; Siscoe, G. L.; Crooker, N. U.

1987-01-01

During southward B(z) periods the open field line region in the ionosphere (polar cap) expands due to increased dayside merging. Ionospheric plasma flow patterns result which can be classified by the sign of the interplanetary magnetic field (IMF) B(y) component. In this paper, a time-dependent ionospheric convection model is constructed to simulate these flows. The model consists of a spiral boundary with a gap in it. The sign of the IMF B(y) component determines the geometry of the gap. A potential is applied across the gap and distributed around the boundary. A flow results which enters the polar cap through the gap and uniformly pushes the boundary outward. Results of the model show that B(y) effects are greatest near the gap and virtually unnoticeable on the nightside of the polar cap. Adding a day-night ionospheric conductivity gradient concentrates the polar cap electric field toward dawn. The resulting flow curvature gives a sunward component that is independent of B(y). These patterns are shown to be consistent with published observations.
The upstream open reading frame of cyclin-dependent kinase inhibitor 1A mRNA negatively regulates translation of the downstream main open reading frame

Energy Technology Data Exchange (ETDEWEB)

Kim, Kyoung Mi; Cho, Hana [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of); Kim, Yoon Ki, E-mail: yk-kim@korea.ac.kr [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of)

2012-08-03

Highlights: Black-Right-Pointing-Pointer CDKN1A mRNA is a bona fide NMD substrate. Black-Right-Pointing-Pointer The uORF of CDKN1A mRNA is efficiently translated. Black-Right-Pointing-Pointer Translation of downstream main ORF is negatively regulated by translation of uORF in CDKN1A mRNA. -- Abstract: The first round of translation occurs on mRNAs bound by nuclear cap-binding complex (CBC), which is composed of nuclear cap-binding protein 80 and 20 (CBP80/20). During this round of translation, aberrant mRNAs are recognized and downregulated in abundance by nonsense-mediated mRNA decay (NMD), which is one of the mRNA quality control mechanisms. Here, our microarray analysis reveals that the level of cyclin-dependent kinase inhibitor 1A (CDKN1A; also known as Waf1/p21) mRNAs increases in cells depleted of cellular NMD factors. Intriguingly, CDKN1A mRNA contains an upstream open reading frame (uORF), which is a NMD-inducing feature. Using chimeric reporter constructs, we find that the uORF of CDKN1A mRNA negatively modulates translation of the main downstream ORF. These findings provide biological insights into the possible role of NMD in diverse biological pathways mediated by CDKN1A.
The eukaryotic translation initiation factor 3 subunit E binds to classical swine fever virus NS5A and facilitates viral replication.

Science.gov (United States)

Liu, Xiaofeng; Wang, Xiaoyu; Wang, Qian; Luo, Mingyang; Guo, Huancheng; Gong, Wenjie; Tu, Changchun; Sun, Jinfu

2018-02-01

Classical swine fever virus (CSFV) NS5A protein is a multifunctional protein, playing critical roles in viral RNA replication, translation and assembly. To further explore its functions in viral replication, interaction of NS5A with host factors was assayed using a his-tag "pull down" assay coupled with shotgun LC-MS/MS. Host protein translation initiation factor 3 subunit E was identified as a binding partner of NS5A, and confirmed by co-immunoprecipitation and co-localization analysis. Overexpression of eIF3E markedly enhanced CSFV genomic replication, viral protein expression and production of progeny virus, and downregulation of eIF3E by siRNA significantly decreased viral proliferation in PK-15 cells. Luciferase reporter assay showed an enhancement of translational activity of the internal ribosome entry site of CSFV by eIF3E and a decrease in cellular translation by NS5A. These data indicate that eIF3E plays an important role in CSFV replication, thereby identifying it as a potential target for inhibition of the virus. Copyright © 2017 Elsevier Inc. All rights reserved.
Implications of carbon cap-and-trade for US voluntary renewable energy markets

International Nuclear Information System (INIS)

Bird, Lori A.; Holt, Edward; Levenstein Carroll, Ghita

2008-01-01

Many consumers today are purchasing renewable energy in large part for the greenhouse gas (GHG) emissions benefits that they provide. Emerging carbon regulation in the US has the potential to affect existing markets for renewable energy. Carbon cap-and-trade programs are now under development in the Northeast under the Regional Greenhouse Gas Initiative (RGGI) and in early stages of development in the West and Midwest. There is increasing discussion about carbon regulation at the national level as well. While renewable energy will likely benefit from carbon cap-and-trade programs because compliance with the cap will increase the costs of fossil fuel generation, cap-and-trade programs can also impact the ability of renewable energy generation to affect overall CO 2 emissions levels and obtain value for those emissions benefits. This paper summarizes key issues for renewable energy markets that are emerging with carbon regulation, such as the implications for emissions benefits claims and voluntary market demand and the use of renewable energy certificates (RECs) in multiple markets. It also explores policy options under consideration for designing carbon policies to enable carbon markets and renewable energy markets to work together
MARK II end cap calorimeter electronics

International Nuclear Information System (INIS)

Jared, R.C.; Haggerty, J.S.; Herrup, D.A.; Kirsten, F.A.; Lee, K.L.; Olson, S.R.; Wood, D.R.

1985-10-01

An end cap calorimeter system has been added to the MARK II detector in preparation for its use at the SLAC Linear Collider. The calorimeter uses 8744 rectangular proportional counter tubes. This paper describes the design features of the data acquisition electronics that has been installed on the calorimeter. The design and use of computer-based test stands for the amplification and signal-shaping components is also covered. A portion of the complete system has been tested in a beam at SLAC. In these initial tests, using only the calibration provided by the test stands, a resolution of 18%/√E was achieved
Control of protein synthesis in Escherichia coli: strain differences in control of translational initiation after energy source shift-down.

Science.gov (United States)

Jacobson, L A; Jen-Jacobson, L

1980-06-01

We have studied the parameters of protein synthesis in a number of Escherichia coli strains after a shift-down from glucose-minimal to succinate-minimal medium. One group of strains, including K-12(lambda) (ATCC 10798) and NF162, showed a postshift translational yield of 50 to 65% and a 2- to 2.5-fold increase in the functional lifetime of general messenger ribonucleic acid. There was no change in the lag time for beta-galactosidase induction in these strains after the shift-down. A second group, including W1 and W2, showed no reduction in translational yield, no change in the functional lifetime of messenger ribonucleic acid, and a 50% increase in the lag time for beta-galactosidase induction. Evidence is presented which indicates that this increased lag time is not the result of a decreased rate of polypeptide chain propagation. A third group of strains, including NF161, CP78, and NF859, showed an intermediate pattern: translational yield was reduced to about 75% of normal, and the messenger ribonucleic acid functional lifetime was increased by about 50%. Calculation of the relative postshift rates of translational initiation gave about 0.2, 1.0, and 0.5, respectively, for the three groups. There was no apparent correlation between the ability to control translation and the genotypes of these strains at the relA, relX, or spoT loci. Measurements of the induction lag for beta-galactosidase during short-term glucose starvation or after a down-shift induced by alpha-methylglucoside indicated that these regimens elicit responses that are physiologically distinct from those elicited by a glucose-to-succinate shift-down.

Targeting eukaryotic translation in mesothelioma cells with an eIF4E-specific antisense oligonucleotide.

Directory of Open Access Journals (Sweden)

Blake A Jacobson

Full Text Available BACKGROUND: Aberrant cap-dependent translation is implicated in tumorigenesis in multiple tumor types including mesothelioma. In this study, disabling the eIF4F complex by targeting eIF4E with eIF4E-specific antisense oligonucleotide (4EASO is assessed as a therapy for mesothelioma. METHODS: Mesothelioma cells were transfected with 4EASO, designed to target eIF4E mRNA, or mismatch-ASO control. Cell survival was measured in mesothelioma treated with 4EASO alone or combined with either gemcitabine or pemetrexed. Levels of eIF4E, ODC, Bcl-2 and β-actin were assessed following treatment. Binding to a synthetic cap-analogue was used to study the strength of eIF4F complex activation following treatment. RESULTS: eIF4E level and the formation of eIF4F cap-complex decreased in response to 4EASO, but not mismatch control ASO, resulting in cleavage of PARP indicating apoptosis. 4EASO treatment resulted in dose dependent decrease in eIF4E levels, which corresponded to cytotoxicity of mesothelioma cells. 4EASO resulted in decreased levels of eIF4E in non-malignant LP9 cells, but this did not correspond to increased cytotoxicity. Proteins thought to be regulated by cap-dependent translation, Bcl-2 and ODC, were decreased upon treatment with 4EASO. Combination therapy of 4EASO with pemetrexed or gemcitabine further reduced cell number. CONCLUSION: 4EASO is a novel drug that causes apoptosis and selectively reduces eIF4E levels, eIF4F complex formation, and proliferation of mesothelioma cells. eIF4E knockdown results in decreased expression of anti-apoptotic and pro-growth proteins and enhances chemosensitivity.
ATLAS electromagnetic end-cap detector

CERN Multimedia

Maximilien Brice

2003-01-01

After the insertion of the first end-cap into this cryostat, the team proceed to the wiring operations. Millions of wires are connected to the electromagnetic calorimeter on this end-cap, whch must be carefully fed out from the detector so that data can be read out. The energy of photons, electrons and positrons will be measured as they pass through the end-cap having been created along the line of the beams in the proton-proton collisions.
Translational Research from an Informatics Perspective

Science.gov (United States)

Bernstam, Elmer; Meric-Bernstam, Funda; Johnson-Throop, Kathy A.; Turley, James P.; Smith, Jack W.

2007-01-01

Clinical and translational research (CTR) is an essential part of a sustainable global health system. Informatics is now recognized as an important en-abler of CTR and informaticians are increasingly called upon to help CTR efforts. The US National Institutes of Health mandated biomedical informatics activity as part of its new national CTR grant initiative, the Clinical and Translational Science Award (CTSA). Traditionally, translational re-search was defined as the translation of laboratory discoveries to patient care (bench to bedside). We argue, however, that there are many other kinds of translational research. Indeed, translational re-search requires the translation of knowledge dis-covered in one domain to another domain and is therefore an information-based activity. In this panel, we will expand upon this view of translational research and present three different examples of translation to illustrate the point: 1) bench to bedside, 2) Earth to space and 3) academia to community. We will conclude with a discussion of our local translational research efforts that draw on each of the three examples.
ATLAS end-cap detector

CERN Multimedia

Maximilien Brice

2003-01-01

Three scientists from the Institute of Nuclear Phyiscs at Novossibirsk with one of the end-caps of the ATLAS detector. The end-caps will be used to detect particles produced in the proton-proton collisions at the heart of the ATLAS experiment that are travelling close to the axis of the two beams.
A Novel Quality Measure and Correction Procedure for the Annotation of Microbial Translation Initiation Sites.

Directory of Open Access Journals (Sweden)

Lex Overmars

Full Text Available The identification of translation initiation sites (TISs constitutes an important aspect of sequence-based genome analysis. An erroneous TIS annotation can impair the identification of regulatory elements and N-terminal signal peptides, and also may flaw the determination of descent, for any particular gene. We have formulated a reference-free method to score the TIS annotation quality. The method is based on a comparison of the observed and expected distribution of all TISs in a particular genome given prior gene-calling. We have assessed the TIS annotations for all available NCBI RefSeq microbial genomes and found that approximately 87% is of appropriate quality, whereas 13% needs substantial improvement. We have analyzed a number of factors that could affect TIS annotation quality such as GC-content, taxonomy, the fraction of genes with a Shine-Dalgarno sequence and the year of publication. The analysis showed that only the first factor has a clear effect. We have then formulated a straightforward Principle Component Analysis-based TIS identification strategy to self-organize and score potential TISs. The strategy is independent of reference data and a priori calculations. A representative set of 277 genomes was subjected to the analysis and we found a clear increase in TIS annotation quality for the genomes with a low quality score. The PCA-based annotation was also compared with annotation with the current tool of reference, Prodigal. The comparison for the model genome of Escherichia coli K12 showed that both methods supplement each other and that prediction agreement can be used as an indicator of a correct TIS annotation. Importantly, the data suggest that the addition of a PCA-based strategy to a Prodigal prediction can be used to 'flag' TIS annotations for re-evaluation and in addition can be used to evaluate a given annotation in case a Prodigal annotation is lacking.
Danish translation of a physical function item bank from the Patient-Reported Outcome Measurement Information System (PROMIS)

DEFF Research Database (Denmark)

Schnohr, Christina W.; Rasmussen, Charlotte L.; Langberg, Henning

2017-01-01

of the Physical Function item bank into Danish. METHODS: We followed the PROMIS standard procedure, including: 1) two independent translations, 2) back translation, 3) independent reviews of translation quality, and 4) cognitive interviews with a representative sample of the adult population from the municipality...
Adiabatic translation factors in slow ion-atom collisions

International Nuclear Information System (INIS)

Vaaben, J.; Taulbjerg, K.

1981-01-01

The general properties of translation factors in slow atomic collisions are discussed. It is emphasised that an acceptable form of translation factors must be conceptually consistent with the basic underlying assumption of the molecular model; i.e. translation factors must relax adiabatically at intermediate and small internuclear separations. A simple physical argument is applied to derive a general parameter-free expression for the translation factor pertinent to an electron in a two-centre Coulomb field. Within the present approach the adiabatic translation factor is considered to be a property of the two-centre field independently of the molecular state under consideration. The generalisation to many-electron systems is therefore readily made. (author)
Translational Repression in Malaria Sporozoites

Science.gov (United States)

Turque, Oliver; Tsao, Tiffany; Li, Thomas; Zhang, Min

2016-01-01

Malaria is a mosquito-borne infectious disease of humans and other animals. It is caused by the parasitic protozoan, Plasmodium. Sporozoites, the infectious form of malaria parasites, are quiescent when they remain in the salivary glands of the Anopheles mosquito until transmission into a mammalian host. Metamorphosis of the dormant sporozoite to its active form in the liver stage requires transcriptional and translational regulations. Here, we summarize recent advances in the translational repression of gene expression in the malaria sporozoite. In sporozoites, many mRNAs that are required for liver stage development are translationally repressed. Phosphorylation of eukaryotic Initiation Factor 2α (eIF2α) leads to a global translational repression in sporozoites. The eIF2α kinase, known as Upregulated in Infectious Sporozoite 1 (UIS1), is dominant in the sporozoite. The eIF2α phosphatase, UIS2, is translationally repressed by the Pumilio protein Puf2. This translational repression is alleviated when sporozoites are delivered into the mammalian host. PMID:28357358
Translational repression in malaria sporozoites

Directory of Open Access Journals (Sweden)

Oliver Turque

2016-04-01

Full Text Available Malaria is a mosquito-borne infectious disease of humans and other animals. It is caused by the parasitic protozoan, Plasmodium. Sporozoites, the infectious form of malaria parasites, are quiescent when they remain in the salivary glands of the Anopheles mosquito until transmission into a mammalian host. Metamorphosis of the dormant sporozoite to its active form in the liver stage requires transcriptional and translational regulations. Here, we summarize recent advances in the translational repression of gene expression in the malaria sporozoite. In sporozoites, many mRNAs that are required for liver stage development are translationally repressed. Phosphorylation of eukaryotic Initiation Factor 2α (eIF2α leads to a global translational repression in sporozoites. The eIF2α kinase, known as Upregulated in Infectious Sporozoite 1 (UIS1, is dominant in the sporozoite. The eIF2α phosphatase, UIS2, is translationally repressed by the Pumilio protein Puf2. This translational repression is alleviated when sporozoites are delivered into the mammalian host.
21 CFR 884.5250 - Cervical cap.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cervical cap. 884.5250 Section 884.5250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... cap. (a) Identification. A cervical cap is a flexible cuplike receptacle that fits over the cervix to...
21 CFR 888.3000 - Bone cap.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Bone cap. 888.3000 Section 888.3000 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3000 Bone cap. (a) Identification. A bone cap is a mushroom...
Genetic ablation of root cap cells in Arabidopsis

OpenAIRE

Tsugeki, Ryuji; Fedoroff, Nina V.

1999-01-01

The root cap is increasingly appreciated as a complex and dynamic plant organ. Root caps sense and transmit environmental signals, synthesize and secrete small molecules and macromolecules, and in some species shed metabolically active cells. However, it is not known whether root caps are essential for normal shoot and root development. We report the identification of a root cap-specific promoter and describe its use to genetically ablate root caps by directing root cap-specific expression of...
Inhibition of Androgen-Independent Prostate Cancer by Estrogenic Compounds Is Associated with Increased Expression of Immune-Related Genes

Directory of Open Access Journals (Sweden)

Ilsa M. Coleman

2006-10-01

Full Text Available The clinical utility of estrogens for treating prostate cancer (CaP was established in the 1940s by Huggins. The classic model of the anti-CaP activity of estrogens postulates an indirect mechanism involving the suppression of androgen production. However, clinical, preclinical studies have shown that estrogens exert growth-inhibitory effects on CaP under low-androgen conditions, suggesting additional modes whereby estrogens affect CaP cells and/or the microenvironment. Here we have investigated the activity of 17β estradiol (E2 against androgen-independent CaP, identified molecular alterations in tumors exposed to E2. E2 treatment inhibited the growth of all four androgen-independent CaP xenografts studied (LuCaP 35V, LuCaP 23.1AI, LuCaP 49, LuCaP 58 in castrated male mice. The molecular basis of growth suppression was studied by cDNA microarray analysis, which indicated that multiple pathways are altered by E2 treatment. Of particular interest are changes in transcripts encoding proteins that mediate immune responses, regulate androgen receptor signaling. In conclusion, our data show that estrogens have powerful inhibitory effects on CaP in vivo in androgendepleted environments, suggest novel mechanisms of estrogen-mediated antitumor activity. These results indicate that incorporating estrogens into CaP treatment protocols could enhance therapeutic efficacy even in cases of advanced disease.
CENTRIFUGE END CAP

Science.gov (United States)

Beams, J.W.; Snoddy, L.B.

1960-08-01

An end cap for ultra-gas centrifuges is designed to impart or remove angular momentum to or from the gas and to bring the entering gas to the temperature of the gas inside the centrifuge. The end cap is provided with slots or fins for adjusting the temperature and the angular momentum of the entering gas to the temperature and momentum of the gas in the centrifuge and is constructed to introduce both the inner and the peripheral stream into the centrifuge.
TRADUCCIÓN DE ACRÓNIMOS Y SIGLAS EN TEXTOS MÉDICOS DE CARDIOLOGÍA / Translation of acronyms and initialisms in medical texts on cardiology

Directory of Open Access Journals (Sweden)

Ana V. Fernández Peraza

2013-01-01

cumplimiento de su función comunicativa fundamental, brindar información útil al personal de la salud. / Abstract Introduction and Objectives: Acronyms and initialisms are frequently used in medical texts. Their translation is not only language-dependent, but also culture-bound. The objective of this research was to analyze the problems associated to the translation from English into Spanish of acronyms and initialisms used in medical texts on Cardiology. Method: This is a qualitative, interpretive, descriptive, synchronic study based on the lexical analysis of acronyms and initialisms in the English source text (ST and the Spanish target text (TT, within the framework of descriptive translation studies. An empirical textual sample of 8 medical articles on Cardiology was analyzed, as well as their corresponding translations into Spanish. Results: In the corpus 83 acronyms and initialisms were identified. Only 15 were identified as acronyms. When analyzing the acronyms and initialisms, it was found that, in most of the cases, suitable solutions were given to the translation problems posed by their use in the TT, and such solutions coincided with the ones proposed in the reviewed literature on the topic. Some difficulties were found, however; they were related to the use of acronyms and initialisms appearing in the ST without their full form or without an explanation, especially those referring to institutions and regional or national organizations. Conclusions: Acronyms and initialisms are not only linguistic forms, but they are also objective phenomena within scientific culture and they are cultural referents. That is why their use and translation imply linguistic as well as extra-linguistic considerations which demand from the translator the use of auxiliary sources and reference materials, including interviews to specialists, to achieve quality and precision in the translated text. This will guarantee the fulfillment of its main communicative function, that is, to provide
THE TURN OF THE MONTH EFFECT CONTINUED: A COMPARISON OF SMALL CAP STOCKS AND LARGE CAP STOCKS

OpenAIRE

Ramsundhar, Shamman

2010-01-01

The purpose of this paper is to investigate whether the turn of the month effect occurs in small cap and large cap stocks and if it occurs in both categories, to determine whether there is a difference in the magnitude. My research, for the period of 1963-2008, based on the CRSP value weighted index, shows that there is a significant turn of the month effect in small and large cap stocks, however the effect is larger in small cap stocks. Furthermore, this effect is not limited to a short time...
An architecture for device independent interfacing

International Nuclear Information System (INIS)

Pace, D.M.

1990-01-01

Achieving device independence for software applications is required for all but a small number of critical real time applications. Device independence is achieved by establishing protocols and building protocol interpreters for the specific devices. Data structures containing pointers to functions provide a flexible architecture for implementing protocol translation. 3 refs., 5 figs
CAP vessel monitoring. Programme, measurement and neutron calculation

International Nuclear Information System (INIS)

Farrugia, J.M.; Nimal, J.C.; Totth, B.; Lloret, R.; Perdreau, R.

1982-03-01

Starting with the design of the CAP (Prototype Advanced NSSS), a programme for pressure vessel monitoring has been prepared, including dosimetry. The dosimetry programme encompasses activation dosimeters (Cu, Nb, Co) and fission dosimeters ( 237 Np, 238 U) installed either inside the pressure vessel with the monitoring test-samples, or in a counting tube outside the pressure vessel. In the first place, a description of the method for neutronic calculation is given; such calculations use the codes ANISN and MERCURE 4 allowing assessment of the neutron spectrum seen by the detectors and the related reaction coefficient. This is followed by a description of the instrumentation. The initial dosimetry results available after the initial operating cycles concur with calculations [fr
The contribution to site core damage frequency from independent occurrences of initiators in two or more units: How low is it?

Energy Technology Data Exchange (ETDEWEB)

Kim, Dong-San; Park, Jin Hee; Lim, Ho Gon [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2016-10-15

Stutzke estimated the site risk by summing the contribution from common cause initiators and the contribution from single-unit initiators. He considered some kinds of multi-unit accident sequences caused by single-unit initiators. However, the contribution from independent occurrences of initiators in two or more units at a site was not taken into account. The purpose of this study is to estimate the contribution to site core damage frequency (CDF) from simultaneous occurrences of independent initiators in two or more units at the same site. Some assumptions and methods used in this analysis are firstly described, and the results and conclusions of the analysis are described. In this study, the contribution to site core damage frequency (CDF) from simultaneous occurrences of independent initiators in two or more units at the same site was estimated. A Korean six-unit site was selected as the reference site and the at-power internal events Level 1 PSA model for an OPR1000 unit at the reference site was used as the base model, and was modified to deal with some major dependencies between units at the site. Specifically, the availability of the AAC D/G, dependencies between offsite power recovery actions in different unis, and inter-unit CCF modeling for risk-significant components such as diesel generators were taken into account. As a result, the sum of dual-unit CDF due to independent occurrences of initiators in two units at the reference site was estimated to be sufficiently low to be neglected.
Overexpression of eIF5 or its protein mimic 5MP perturbs eIF2 function and induces ATF4 translation through delayed re-initiation.

Science.gov (United States)

Kozel, Caitlin; Thompson, Brytteny; Hustak, Samantha; Moore, Chelsea; Nakashima, Akio; Singh, Chingakham Ranjit; Reid, Megan; Cox, Christian; Papadopoulos, Evangelos; Luna, Rafael E; Anderson, Abbey; Tagami, Hideaki; Hiraishi, Hiroyuki; Slone, Emily Archer; Yoshino, Ken-Ichi; Asano, Masayo; Gillaspie, Sarah; Nietfeld, Jerome; Perchellet, Jean-Pierre; Rothenburg, Stefan; Masai, Hisao; Wagner, Gerhard; Beeser, Alexander; Kikkawa, Ushio; Fleming, Sherry D; Asano, Katsura

2016-10-14

ATF4 is a pro-oncogenic transcription factor whose translation is activated by eIF2 phosphorylation through delayed re-initiation involving two uORFs in the mRNA leader. However, in yeast, the effect of eIF2 phosphorylation can be mimicked by eIF5 overexpression, which turns eIF5 into translational inhibitor, thereby promoting translation of GCN4, the yeast ATF4 equivalent. Furthermore, regulatory protein termed eIF5-mimic protein (5MP) can bind eIF2 and inhibit general translation. Here, we show that 5MP1 overexpression in human cells leads to strong formation of 5MP1:eIF2 complex, nearly comparable to that of eIF5:eIF2 complex produced by eIF5 overexpression. Overexpression of eIF5, 5MP1 and 5MP2, the second human paralog, promotes ATF4 expression in certain types of human cells including fibrosarcoma. 5MP overexpression also induces ATF4 expression in Drosophila The knockdown of 5MP1 in fibrosarcoma attenuates ATF4 expression and its tumor formation on nude mice. Since 5MP2 is overproduced in salivary mucoepidermoid carcinoma, we propose that overexpression of eIF5 and 5MP induces translation of ATF4 and potentially other genes with uORFs in their mRNA leaders through delayed re-initiation, thereby enhancing the survival of normal and cancer cells under stress conditions. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Independent power and cogeneration in Ontario's new competitive electricity market

International Nuclear Information System (INIS)

Barnstable, A.G.

1999-01-01

The factors influencing the initial market pricing in the early years of Ontario's new electricity market were discussed with particular insight on the potential for near term development of independent power and cogeneration. The major factors influencing prices include: (1) no increase in retail prices, (2) financial restructuring of Ontario Hydro, (3) the Market Power Mitigation Agreement, (4) tighter power plant emissions standards, and (5) an electricity supply and demand balance. Generation competition is not expected to influence market pricing in the early years of the new electricity market. Prices will instead reflect the restructuring decisions of the Ontario government. The decision to have Ontario Power Generation Inc. (OPGI) as a single generator for Ontario Hydro's generation assets will ensure that average spot market pricing in the early market years will be close to a 3.8 c/kWh revenue cap
Slow Manifolds and Multiple Equilibria in Stratocumulus-Capped Boundary Layers

Directory of Open Access Journals (Sweden)

Junya Uchida

2010-12-01

Full Text Available In marine stratocumulus-capped boundary layers under strong inversions, the timescale for thermodynamic adjustment is roughly a day, much shorter than the multiday timescale for inversion height adjustment. Slow-manifold analysis is introduced to exploit this timescale separation when boundary layer air columns experience only slow changes in their boundary conditions. Its essence is that the thermodynamic structure of the boundary layer remains approximately slaved to its inversion height and the instantaneous boundary conditions; this slaved structure determines the entrainment rate and hence the slow evolution of the inversion height. Slow-manifold analysis is shown to apply to mixed-layer model and large-eddy simulations of an idealized nocturnal stratocumulus- capped boundary layer; simulations with different initial inversion heights collapse onto single relationships of cloud properties with inversion height. Depending on the initial inversion height, the simulations evolve toward a shallow thin-cloud boundary layer or a deep, well-mixed thick cloud boundary layer. In the large-eddy simulations, these evolutions occur on two separate slow manifolds (one of which becomes unstable if cloud droplet concentration is reduced. Applications to analysis of stratocumulus observations and to pockets of open cells and ship tracks are proposed.
Initiation of protein synthesis in bacteria

DEFF Research Database (Denmark)

Laursen, Brian Søgaard; Sørensen, Hans Peter; Mortensen, Kim Kusk

2005-01-01

Valuable information on translation initiation is available from biochemical data and recently solved structures. We present a detailed description of current knowledge about the structure, function, and interactions of the individual components involved in bacterial translation initiation. The f...
A Systematic Translation and Cultural Adaptation Process for Three-Factor Eating Questionnaire (TFEQ-R21).

Science.gov (United States)

Rosnah, I; Noor Hassim, I; Shafizah, A S

2013-10-01

The Three-Factor Eating Questionnaire was first constructed to measure eating behavior in an English population in the United States. It has been validated and translated for various populations in different languages. The aim of this article is to describe a systematic process for translating the questionnaire from English to Malay language. The report of the International Society for Pharmacoeconomics and Outcome Research (ISPOR) Task Force was used as the basis for the systematic translation process. The process began with preparation; followed by forward translation (2 independent translators), reconciliation, back translation (2 independent translators), back translation review, harmonization, cognitive debriefing, review of cognitive debriefing results and finalization, proofreading; and ended with the final report. Four independent Malay translators who fluent in English and reside in Malaysia were involved in the process. A team of health care researchers had assisted the review of the new translated questionnaires. Majority of the TFEQ-R21 items were experiencing, conceptually and semantically equivalence between original English and translated English. However, certain phrase such as "feels like bottomless pit" was difficult to translate by forward translators. Cognitive debriefing was a very helpful process to ensure the TFEQ-R21 Malay version was appropriate in term of wording and culturally accepted. A total of four redundant comments in regards to response scale wording, word confusion and wording arrangement. The systematic translation process is a way to reduce the linguistic discrepancies between the English and Malay language in order to promote equivalence and culturally adapted TFEQ-R21 questionnaire.
Early results of patellofemoral inlay resurfacing arthroplasty using the HemiCap Wave prosthesis.

Science.gov (United States)

Patel, Akash; Haider, Zakir; Anand, Amarjit; Spicer, Dominic

2017-01-01

Common surgical treatment options for isolated patellofemoral osteoarthritis include arthroscopic procedures, total knee replacement and patellofemoral replacement. The HemiCap Wave patellofemoral resurfacing prosthesis is a novel inlay design introduced in 2009 with scarce published data on its functional outcomes. We aim to prospectively evaluate early functional outcomes and complications, for patients undergoing a novel inlay resurfacing arthroplasty for isolated patellofemoral arthrosis in an independent centre. From 2010 to 2013, 16 consecutive patients underwent patellofemoral resurfacing procedures using HemiCap Wave (Arthrosurface Inc., Franklin, Massachusetts, USA) for anterior knee pain with confirmed radiologically and/or arthroscopically isolated severe patellofemoral arthrosis. Standardized surgical technique, as recommended by the implant manufacturer, was followed. Outcome measures included range of movement, functional knee scores (Oxford Knee Score (OKS), Knee Injury and Osteoarthritis Outcome Score (KOOS) and Short Form-36 (SF-36)), radiographic disease progression, revision rates and complications. Eight men and eight women underwent patellofemoral HemiCap Wave resurfacing, with an average age of 63 years (range: 46-83). Average follow-up was 24.1 months (6-34). Overall, post-operative scores were excellent. There was a statistically significant improvement in the post-operative OKS, KOOS and SF-36 scores ( p patellofemoral resurfacing prosthesis has excellent early results in terms of functional outcomes, radiological outcomes and low complication rates. At the very least, early results show that the HemiCap Wave is comparable to more established onlay prostheses. The HemiCap Wave thus provides a safe and effective surgical option in the treatment of isolated patellofemoral osteoarthritis in selected patients.
Overview of the Inland California Translational Consortium

Science.gov (United States)

Malkas, Linda H.

2017-05-01

The mission of the Inland California Translational Consortium (ICTC), an independent research consortium comprising a unique hub of regional institutions (City of Hope [COH], California Institute of Technology [Caltech], Jet Propulsion Laboratory [JPL], University of California Riverside [UCR], and Claremont Colleges Keck Graduate Institute [KGI], is to institute a new paradigm within the academic culture to accelerate translation of innovative biomedical discoveries into clinical applications that positively affect human health and life. The ICTC actively supports clinical translational research as well as the implementation and advancement of novel education and training models for the translation of basic discoveries into workable products and practices that preserve and improve human health while training and educating at all levels of the workforce using innovative forward-thinking approaches.
Adaptive changes in alphavirus mRNA translation allowed colonization of vertebrate hosts.

Science.gov (United States)

Ventoso, Iván

2012-09-01

Members of the Alphavirus genus are arboviruses that alternate replication in mosquitoes and vertebrate hosts. In vertebrate cells, the alphavirus resists the activation of antiviral RNA-activated protein kinase (PKR) by the presence of a prominent RNA structure (downstream loop [DLP]) located in viral 26S transcripts, which allows an eIF2-independent translation initiation of these mRNAs. This article shows that DLP structure is essential for replication of Sindbis virus (SINV) in vertebrate cell lines and animals but is dispensable for replication in insect cells, where no ortholog of the vertebrate PKR gene has been found. Sequence comparisons and structural RNA analysis revealed the evolutionary conservation of DLP in SINV and predicted the existence of equivalent DLP structures in many members of the Alphavirus genus. A mutant SINV lacking the DLP structure evolved in murine cells to recover a wild-type phenotype by creating an alternative structure in the RNA that restored the translational independence for eIF2. Genetic, phylogenetic, and biochemical data presented here support an evolutionary scenario for the natural history of alphaviruses, in which the acquisition of DLP structure in their mRNAs probably allowed the colonization of vertebrate host and the consequent geographic expansion of some of these viruses worldwide.
Effects of rooting and tree growth of selected woodland species on cap integrity in a mineral capped landfill site.

Science.gov (United States)

Hutchings, T R; Moffat, A J; Kemp, R A

2001-06-01

The above and below ground growth of three tree species (Alnus glutinosa, Pinus nigra var. maritima and Acer pseudoplatanus) was studied on a containment landfill site at Waterford, Hertfordshire, UK. Tree root architecture was studied using soil inspection pits excavated next to 12 trees of each species and mapped in detail. Tree height was related to soil thickness over the compacted mineral cap. No roots entered the cap where soil thickness was 1.3 m, but a few roots, especially of alder, were observed within it when the soil cover was 1.0 m or less. Micromorphological analysis of undisturbed samples of the mineral cap suggested that roots exploited weaknesses in the cap rather than actively causing penetration into it. Alder roots were more tolerant of anaerobic conditions within the cap than the other species examined. The results confirm that mineral caps should be covered by 1.5 m of soil or soil-forming material if tree establishment is intended over a restored landfill site, unless protected by other parts of a composite capping system.
Euphemism vs explicitness: A corpus-based analysis of translated ...

African Journals Online (AJOL)

This article examines the governing initial norms, namely explicitness and euphemism in English source texts and Ndebele translations, focusing on how these norms influenced the strategies chosen by the Ndebele translators in the translation of taboo terms. In the article, a corpus-based approach is used to identify head ...
Actor or arena: contrasting translations of a law on interorganizational integration.

Science.gov (United States)

Andersson, Johanna; Löfström, Mikael; Axelsson, Susanna Bihari; Axelsson, Runo

2012-01-01

A Swedish framework law has enabled integration between public agencies in vocational rehabilitation. With the support of this law, coordination associations can be formed to fund and organize joint activities. The purpose of this study is to describe and analyze how the law has been interpreted and translated into local coordination associations and how local institutional logics have developed to guide the organization of these associations. Data was collected through observations of meetings within two coordination associations and supplemented with documents. The material was analyzed by compilation and examination of data from field notes, whereupon the most important aspects were crystallized and framed with institutional organization theory. Two different translations of the law were seen in the associations studied: the association as an independent actor, and as an arena for its member organizations. Two subsequent institutional logics have developed, influencing decisions on autonomy, objectives and rationality for initiating and organizing in the two associations and their activities. The institutional logics are circular, further enhancing the different translations creating different forms of integration. Both forms of integration are legitimate, but the different translations have created integration with different degrees of autonomy in relation to the member organizations. Only a long-term analysis can show whether one form of integration is more functional than the other. This article is based on an extensive material providing insights into a form of interorganizational integration which has been scarcely researched. The findings show how different translations can influence the integration of welfare services.
[Cryopyrine-associated periodic syndrome: CAPS seen from adulthood].

Science.gov (United States)

Koné-Paut, I

2015-04-01

Cryopyrin-associated periodic syndrome is a rare hereditary periodic fever syndrome for which, the genetic mechanism, mutation in the NLRP3 gene, has allowed to gather 3 clinical phenotypes (familial cold urticaria [FCAS], Muckle-Wells syndrome [MWS], and chronic infantile neurological cutaneous and articular syndrome [CINCA]) initially described independently, and to discover the NLRP3 inflammasome, a key receptor of the innate immunity, which regulates the interleukine-1β secretion into the mononuclear cells. The clinical manifestation of CAPS : urticaria-like skin rash, eyes redness, myalgia and sensory deafness are not specific, if considered separately, and that often leads to a wandering diagnosis through a complex medical journey including various specialists. The diagnostic delay is deleterious to patients compromising their quality of life and exposing them to neurosensory complications and renal failure by secondary amyloidosis. The paediatric onset of disease, the family history, the trigger of symptoms by the cold, and the recognition of the skin rash as neutrophilic are important clues before diagnostic confirmation by genetic testing. Interleukine-1 blockade is the only effective treatment of CAPS symptoms which often may stabilize (rarely regression) the sensory involvement and in some cases may allow the regression of secondary amyloidosis. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.
Evaluation of the "Foundations in Knowledge Translation" training initiative: preparing end users to practice KT.

Science.gov (United States)

Park, Jamie S; Moore, Julia E; Sayal, Radha; Holmes, Bev J; Scarrow, Gayle; Graham, Ian D; Jeffs, Lianne; Timmings, Caitlyn; Rashid, Shusmita; Johnson, Alekhya Mascarenhas; Straus, Sharon E

2018-04-25

Current knowledge translation (KT) training initiatives are primarily focused on preparing researchers to conduct KT research rather than on teaching KT practice to end users. Furthermore, training initiatives that focus on KT practice have not been rigorously evaluated and have focused on assessing short-term outcomes and participant satisfaction only. Thus, there is a need for longitudinal training evaluations that assess the sustainability of training outcomes and contextual factors that may influence outcomes. We evaluated the KT training initiative "Foundations in KT" using a mixed-methods longitudinal design. "Foundations in KT" provided training in KT practice and included three tailored in-person workshops, coaching, and an online platform for training materials and knowledge exchange. Two cohorts were included in the study (62 participants, including 46 "Foundations in KT" participants from 16 project teams and 16 decision-maker partners). Participants completed self-report questionnaires, focus groups, and interviews at baseline and at 6, 12, 18, and 24 months after the first workshop. Participant-level outcomes include survey results which indicated that participants' self-efficacy in evidence-based practice (F(1,8.9) = 23.7, p = 0.001, n = 45), KT activities (F(1,23.9) = 43.2, p training initiative helped participants achieve their KT project objectives, plan their projects, and solve problems over time. Contextual factors include teams with high self-reported organizational capacity and commitment to implement at the start of their project had buy-in from upper management that resulted in secured funding and resources for their project. Training initiative outcomes include participants who applied the KT knowledge and skills they learned to other projects by sharing their knowledge informally with coworkers. Sustained spread of KT practice was observed with five teams at 24 months. We completed a longitudinal evaluation of a KT
Translational initiation in Leishmania tarentolae and Phytomonas serpens (Kinetoplastida) is strongly influenced by pre-ATG triplet and its 5´ sequence context

Czech Academy of Sciences Publication Activity Database

Lukeš, Julius; Paris, Zdeněk; Regmi, Sandesh; Breitling, R.; Mureev, S.; Kushnir, S.; Pyatkov, K.; Jirků, Milan; Alexandrov, K. A.

2006-01-01

Roč. 148, č. 2 (2006), s. 125-132 ISSN 0166-6851 R&D Projects: GA AV ČR 1QS600220554 Grant - others:Deutsche Forschungsgemeinschaft(DE) AL484/5-3 Institutional research plan: CEZ:AV0Z60220518 Keywords : Kinetoplastida * translation * initiation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.641, year: 2006
Analyses of hydraulic performance of velocity caps

DEFF Research Database (Denmark)

Christensen, Erik Damgaard; Degn Eskesen, Mark Chr.; Buhrkall, Jeppe

2014-01-01

The hydraulic performance of a velocity cap has been investigated. Velocity caps are often used in connection with offshore intakes. CFD (computational fluid dynamics) examined the flow through the cap openings and further down into the intake pipes. This was combined with dimension analyses...
Suppression of Translation During in vitro Maturation of Pig Oocytes Despite Enhanced Formation of Cap-binding Protein Complex eIF4F and 4E-BP1 hyperphosphorylation.

Czech Academy of Sciences Publication Activity Database

Ellederová, Zdeňka; Kovářová, Hana; Melo Sterza, F.; Livingstone, M.; Tomek, W.; Kubelka, Michal

2006-01-01

Roč. 73, 1 (2006), s. 68-76 ISSN 1040-452X R&D Projects: GA ČR GA301/00/0781; GA ČR GA524/04/0104 Grant - others:Deutche Forschungsgemeinschaft(DE) 463TSE113/28 Institutional research plan: CEZ:AV0Z50450515 Keywords : meiosis * translation initiation * eIF-4E Subject RIV: ED - Physiology Impact factor: 2.379, year: 2006
49 CFR 230.41 - Flexible staybolts with caps.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Flexible staybolts with caps. 230.41 Section 230... Appurtenances Staybolts § 230.41 Flexible staybolts with caps. (a) General. Flexible staybolts with caps shall have their caps removed during every 5th annual inspection for the purpose of inspecting the bolts for...
Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

DEFF Research Database (Denmark)

NN, NN; Mugavero, Michael J; May, Margaret

2008-01-01

, nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone. MAIN OUTCOME MEASURES: Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation.......58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1......OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between...
IRESPred: Web Server for Prediction of Cellular and Viral Internal Ribosome Entry Site (IRES)

Science.gov (United States)

Kolekar, Pandurang; Pataskar, Abhijeet; Kulkarni-Kale, Urmila; Pal, Jayanta; Kulkarni, Abhijeet

2016-01-01

Cellular mRNAs are predominantly translated in a cap-dependent manner. However, some viral and a subset of cellular mRNAs initiate their translation in a cap-independent manner. This requires presence of a structured RNA element, known as, Internal Ribosome Entry Site (IRES) in their 5′ untranslated regions (UTRs). Experimental demonstration of IRES in UTR remains a challenging task. Computational prediction of IRES merely based on sequence and structure conservation is also difficult, particularly for cellular IRES. A web server, IRESPred is developed for prediction of both viral and cellular IRES using Support Vector Machine (SVM). The predictive model was built using 35 features that are based on sequence and structural properties of UTRs and the probabilities of interactions between UTR and small subunit ribosomal proteins (SSRPs). The model was found to have 75.51% accuracy, 75.75% sensitivity, 75.25% specificity, 75.75% precision and Matthews Correlation Coefficient (MCC) of 0.51 in blind testing. IRESPred was found to perform better than the only available viral IRES prediction server, VIPS. The IRESPred server is freely available at http://bioinfo.net.in/IRESPred/. PMID:27264539
Theoretical model of polar cap auroral arcs

International Nuclear Information System (INIS)

Kan, J.R.; Burke, W.J.; USAF, Bedford, MA)

1985-01-01

A theory of the polar cap auroral arcs is proposed under the assumption that the magnetic field reconnection occurs in the cusp region on tail field lines during northward interplanetary magnetic field (IMF) conditions. Requirements of a convection model during northward IMF are enumerated based on observations and fundamental theoretical considerations. The theta aurora can be expected to occur on the closed field lines convecting sunward in the central polar cap, while the less intense regular polar cap arcs can occur either on closed or open field lines. The dynamo region for the polar cap arcs is required to be on closed field lines convecting tailward in the plasma sheet which is magnetically connected to the sunward convection in the central polar cap. 43 references
5'-Phospho-RNA Acceptor Specificity of GDP Polyribonucleotidyltransferase of Vesicular Stomatitis Virus in mRNA Capping.

Science.gov (United States)

Ogino, Minako; Ogino, Tomoaki

2017-03-15

The GDP polyribonucleotidyltransferase (PRNTase) domain of the multifunctional L protein of rhabdoviruses, such as vesicular stomatitis virus (VSV) and rabies virus, catalyzes the transfer of 5'-phospho-RNA (pRNA) from 5'-triphospho-RNA (pppRNA) to GDP via a covalent enzyme-pRNA intermediate to generate a 5'-cap structure (GpppA). Here, using an improved oligo-RNA capping assay with the VSV L protein, we showed that the Michaelis constants for GDP and pppAACAG (VSV mRNA-start sequence) are 0.03 and 0.4 μM, respectively. A competition assay between GDP and GDP analogues in the GpppA formation and pRNA transfer assay using GDP analogues as pRNA acceptors indicated that the PRNTase domain recognizes the C-2-amino group, but not the C-6-oxo group, N-1-hydrogen, or N-7-nitrogen, of GDP for the cap formation. 2,6-Diaminopurine-riboside (DAP), 7-deazaguanosine (7-deaza-G), and 7-methylguanosine (m 7 G) diphosphates efficiently accepted pRNA, resulting in the formation of DAPpppA, 7-deaza-GpppA, and m 7 GpppA (cap 0), respectively. Furthermore, either the 2'- or 3'-hydroxyl group of GDP was found to be required for efficient pRNA transfer. A 5'-diphosphate form of antiviral ribavirin weakly inhibited the GpppA formation but did not act as a pRNA acceptor. These results indicate that the PRNTase domain has a unique guanosine-binding mode different from that of eukaryotic mRNA capping enzyme, guanylyltransferase. IMPORTANCE mRNAs of nonsegmented negative-strand (NNS) RNA viruses, such as VSV, possess a fully methylated cap structure, which is required for mRNA stability, efficient translation, and evasion of antiviral innate immunity in host cells. GDP polyribonucleotidyltransferase (PRNTase) is an unconventional mRNA capping enzyme of NNS RNA viruses that is distinct from the eukaryotic mRNA capping enzyme, guanylyltransferase. In this study, we studied the pRNA acceptor specificity of VSV PRNTase using various GDP analogues and identified chemical groups of GDP as

Translation, Cultural Adaptation and Validation of the Simple Shoulder Test to Spanish

OpenAIRE

Arcuri, Francisco; Barclay, Fernando; Nacul, Ivan

2015-01-01

Background: The validation of widely used scales facilitates the comparison across international patient samples. Objective: The objective was to translate, culturally adapt and validate the Simple Shoulder Test into Argentinian Spanish. Methods: The Simple Shoulder Test was translated from English into Argentinian Spanish by two independent translators, translated back into English and evaluated for accuracy by an expert committee to correct the possible discrepancies. It was then administer...
Initial conditions for critical Higgs inflation

Science.gov (United States)

Salvio, Alberto

2018-05-01

It has been pointed out that a large non-minimal coupling ξ between the Higgs and the Ricci scalar can source higher derivative operators, which may change the predictions of Higgs inflation. A variant, called critical Higgs inflation, employs the near-criticality of the top mass to introduce an inflection point in the potential and lower drastically the value of ξ. We here study whether critical Higgs inflation can occur even if the pre-inflationary initial conditions do not satisfy the slow-roll behavior (retaining translation and rotation symmetries). A positive answer is found: inflation turns out to be an attractor and therefore no fine-tuning of the initial conditions is necessary. A very large initial Higgs time-derivative (as compared to the potential energy density) is compensated by a moderate increase in the initial field value. These conclusions are reached by solving the exact Higgs equation without using the slow-roll approximation. This also allows us to consistently treat the inflection point, where the standard slow-roll approximation breaks down. Here we make use of an approach that is independent of the UV completion of gravity, by taking initial conditions that always involve sub-planckian energies.
Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs

OpenAIRE

Rong, Liwei; Livingstone, Mark; Sukarieh, Rami; Petroulakis, Emmanuel; Gingras, Anne-Claude; Crosby, Katherine; Smith, Bradley; Polakiewicz, Roberto D.; Pelletier, Jerry; Ferraiuolo, Maria A.; Sonenberg, Nahum

2008-01-01

Eukaryotic initiation factor (eIF) 4E, the mRNA 5′-cap-binding protein, mediates the association of eIF4F with the mRNA 5′-cap structure to stimulate cap-dependent translation initiation in the cytoplasm. The assembly of eIF4E into the eIF4F complex is negatively regulated through a family of repressor proteins, called the eIF4E-binding proteins (4E-BPs). eIF4E is also present in the nucleus, where it is thought to stimulate nuclear-cytoplasmic transport of certain mRNAs. eIF4E is transported...
Netrin-1 Protects Hepatocytes Against Cell Death Through Sustained Translation During the Unfolded Protein Response.

Science.gov (United States)

Lahlali, Thomas; Plissonnier, Marie-Laure; Romero-López, Cristina; Michelet, Maud; Ducarouge, Benjamin; Berzal-Herranz, Alfredo; Zoulim, Fabien; Mehlen, Patrick; Parent, Romain

2016-05-01

Netrin-1, a multifunctional secreted protein, is up-regulated in cancer and inflammation. Netrin-1 blocks apoptosis induced by the prototypical dependence receptors deleted in colorectal carcinoma and uncoordinated phenotype-5. Although the unfolded protein response (UPR) triggers apoptosis on exposure to stress, it first attempts to restore endoplasmic reticulum homeostasis to foster cell survival. Importantly, UPR is implicated in chronic liver conditions including hepatic oncogenesis. Netrin-1's implication in cell survival on UPR in this context is unknown. Isolation of translational complexes, determination of RNA secondary structures by selective 2'-hydroxyl acylation and primer extension/dimethyl sulfate, bicistronic constructs, as well as conventional cell biology and biochemistry approaches were used on in vitro-grown hepatocytic cells, wild-type, and netrin-1 transgenic mice. HepaRG cells constitute a bona fide model for UPR studies in vitro through adequate activation of the 3 sensors of the UPR (protein kinase RNA-like endoplasmic reticulum kinase (PERK)), inositol requiring enzyme 1α (IRE1α), and activated transcription factor 6 (ATF6). The netrin-1 messenger RNA 5'-end was shown to fold into a complex double pseudoknot and bear E-loop motifs, both of which are representative hallmarks of related internal ribosome entry site regions. Cap-independent translation of netrin 5' untranslated region-driven luciferase was observed on UPR in vitro. Unlike several structurally related oncogenic transcripts (l-myc, c-myc, c-myb), netrin-1 messenger RNA was selected for translation during UPR both in human hepatocytes and in mice livers. Depletion of netrin-1 during UPR induces apoptosis, leading to cell death through an uncoordinated phenotype-5A/C-mediated involvement of protein phosphatase 2A and death-associated protein kinase 1 in vitro and in netrin transgenic mice. UPR-resistant, internal ribosome entry site-driven netrin-1 translation leads to
The mechanism of translation initiation on Aichivirus RNA mediated by a novel type of picornavirus IRES.

Science.gov (United States)

Yu, Yingpu; Sweeney, Trevor R; Kafasla, Panagiota; Jackson, Richard J; Pestova, Tatyana V; Hellen, Christopher Ut

2011-08-26

Picornavirus mRNAs contain IRESs that sustain their translation during infection, when host protein synthesis is shut off. The major classes of picornavirus IRESs (Types 1 and 2) have distinct structures and sequences, but initiation on both is determined by their specific interaction with eIF4G. We report here that Aichivirus (AV), a member of the Kobuvirus genus of Picornaviridae, contains an IRES that differs structurally from Type 1 and Type 2 IRESs. Its function similarly involves interaction with eIF4G, but its eIF4G-interacting domain is structurally distinct, although it contains an apical eIF4G-interacting motif similar to that in Type 2 IRESs. Like Type 1 and Type 2 IRESs, AV IRES function is enhanced by pyrimidine tract-binding protein (PTB), but the pattern of PTB's interaction with each of these IRESs is distinct. Unlike all known IRESs, the AV IRES is absolutely dependent on DHX29, a requirement imposed by sequestration of its initiation codon in a stable hairpin.
Synthesis of tritium or deuterium labelled 19-nor-3. cap alpha. -hydroxy-5. cap alpha. -androstan-17-one from nortestosterone

Energy Technology Data Exchange (ETDEWEB)

Protiva, J; Klinotova, E [Karlova Univ., Prague (Czechoslovakia). Prirodovedecka Fakulta; Filip, J [Ustav pro Vyzkum, Vyrobu a Vyuziti Radioisotopu, Prague (Czechoslovakia); Hampl, R [Research Inst. of Endocrinology, Praha (Czechoslovakia)

1982-10-20

Tritium and/or deuterium (5-H) labelled 19-nor-3..cap alpha..-hydroxy-5..cap alpha..-androstan-17-one (norandrosterone) was prepared from nortestosterone in view to use it as a radioligand for radioimmunoassay of the main nortestosterone metabolites. Based upon model experiments using testosterone and deuterium labelling, the following four step procedure was established: nortestosterone was oxidized with pyridine chlorochromate and the resulting 19-nor-4-androsten-3,17-dione was tritiated with tritium gas under catalysis with tris(triphenylphosphine)rhodium chloride to give (4,5..cap alpha..-/sup 3/H)19-nor-5..cap alpha..-androstan-3,17-dione. A selective reduction of the latter compound yielded (5-/sup 3/H)19-nor-3..cap alpha..-hydroxy-5..cap alpha..-androstan-17-one of the molar radioactivity 0.3 TBq (8.15 Ci)/mmol.
The Impact of Machine Translation and Computer-aided Translation on Translators

Science.gov (United States)

Peng, Hao

2018-03-01

Under the context of globalization, communications between countries and cultures are becoming increasingly frequent, which make it imperative to use some techniques to help translate. This paper is to explore the influence of computer-aided translation on translators, which is derived from the field of the computer-aided translation (CAT) and machine translation (MT). Followed by an introduction to the development of machine and computer-aided translation, it then depicts the technologies practicable to translators, which are trying to analyze the demand of designing the computer-aided translation so far in translation practice, and optimize the designation of computer-aided translation techniques, and analyze its operability in translation. The findings underline the advantages and disadvantages of MT and CAT tools, and the serviceability and future development of MT and CAT technologies. Finally, this thesis probes into the impact of these new technologies on translators in hope that more translators and translation researchers can learn to use such tools to improve their productivity.
7 CFR 1714.7 - Interest rate cap.

Science.gov (United States)

2010-01-01

... 7 Agriculture 11 2010-01-01 2010-01-01 false Interest rate cap. 1714.7 Section 1714.7 Agriculture... PRE-LOAN POLICIES AND PROCEDURES FOR INSURED ELECTRIC LOANS General § 1714.7 Interest rate cap. Except... section, or both the rate disparity test for the interest rate cap and the consumer income test set forth...
20 CFR 606.22 - Application for cap.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Application for cap. 606.22 Section 606.22... Reduction § 606.22 Application for cap. (a) Application. (1) The Governor of the State shall make... a State requests a cap on tax credit reduction. The Governor is required to notify the Department on...
Method of independent timesteps in the numerical solution of initial value problems

International Nuclear Information System (INIS)

Porter, A.P.

1976-01-01

In the numerical solution of initial-value problems in several independent variables, the timestep is controlled, especially in the presence of shocks, by a small portion of the logical mesh, what one may call the crisis zone. One is frustrated by the necessity of doing in the whole mesh frequent calculations required by only a small part of the mesh. It is shown that it is possible to choose different timesteps natural to different parts of the mesh and to advance each zone in time only as often as is appropriate to that zone's own natural timestep. Prior work is reviewed and for the first time an investigation of the conditions for well-posedness, consistency and stability in independent timesteps is presented; a new method results. The prochronic and parachronic Cauchy surfaces are identified; and the reasons (well-posedness) for constraining the Cauchy surfaces to be prochronic (as distinct from the method of Grandey), that is, to lie prior to the time of the crisis zone (the zone of least timestep), are indicated. Stability (in the maximum norm) of parabolic equations and (in the L2 norm) of hyperbolic equations is reviewed, without restricting the treatment to linear equations or constant coefficients, and stability of the new method is proven in this framework. The details of the method of independent timesteps, the rules for choosing timesteps and for deciding when to update and when to skip zones, and the method of joining adjacent regions of differing timestep are described. The stability of independent timestep difference schemes is analyzed and exhibited. The economic advantages of the method, which often amount to an order-of-magnitude decrease in running time relative to conventional or implicit difference methods, are noted
Method of independent timesteps in the numerical solution of initial value problems

Energy Technology Data Exchange (ETDEWEB)

Porter, A.P.

1976-07-21

In the numerical solution of initial-value problems in several independent variables, the timestep is controlled, especially in the presence of shocks, by a small portion of the logical mesh, what one may call the crisis zone. One is frustrated by the necessity of doing in the whole mesh frequent calculations required by only a small part of the mesh. It is shown that it is possible to choose different timesteps natural to different parts of the mesh and to advance each zone in time only as often as is appropriate to that zone's own natural timestep. Prior work is reviewed and for the first time an investigation of the conditions for well-posedness, consistency and stability in independent timesteps is presented; a new method results. The prochronic and parachronic Cauchy surfaces are identified; and the reasons (well-posedness) for constraining the Cauchy surfaces to be prochronic (as distinct from the method of Grandey), that is, to lie prior to the time of the crisis zone (the zone of least timestep), are indicated. Stability (in the maximum norm) of parabolic equations and (in the L2 norm) of hyperbolic equations is reviewed, without restricting the treatment to linear equations or constant coefficients, and stability of the new method is proven in this framework. The details of the method of independent timesteps, the rules for choosing timesteps and for deciding when to update and when to skip zones, and the method of joining adjacent regions of differing timestep are described. The stability of independent timestep difference schemes is analyzed and exhibited. The economic advantages of the method, which often amount to an order-of-magnitude decrease in running time relative to conventional or implicit difference methods, are noted.
IAA transport in corn roots includes the root cap

International Nuclear Information System (INIS)

Hasenstein, K.H.

1989-01-01

In earlier reports we concluded that auxin is the growth regulator that controls gravicurvature in roots and that the redistribution of auxin occurs within the root cap. Since other reports did not detect auxin in the root cap, we attempted to confirm the IAA does move through the cap. Agar blocks containing 3 H-IAA were applied to the cut surface of 5 mm long apical segments of primary roots of corn (mo17xB73). After 30 to 120 min radioactivity (RA) of the cap and root tissue was determined. While segments suspended in water-saturated air accumulated very little RA in the cap, application of 0.5 μ1 of dist. water to the cap (=controls) increased RA of the cap dramatically. Application to the cap of 0.5 μ1 of sorbitol or the Ca 2+ chelator EGTA reduced cap RA to 46% and 70% respectively compared to water, without affecting uptake. Control root segments gravireacted faster than non-treated or osmoticum or EGTA treated segments. The data indicate that both the degree of hydration and calcium control the amount of auxin moving through the cap
Early sex work initiation independently elevates odds of HIV infection and police arrest among adult sex workers in a Canadian setting.

Science.gov (United States)

Goldenberg, Shira M; Chettiar, Jill; Simo, Annick; Silverman, Jay G; Strathdee, Steffanie A; Montaner, Julio S G; Shannon, Kate

2014-01-01

To explore factors associated with early sex work initiation and model the independent effect of early initiation on HIV infection and prostitution arrests among adult sex workers (SWs). Baseline data (2010-2011) were drawn from a cohort of SWs who exchanged sex for money within the last month and were recruited through time location sampling in Vancouver, Canada. Analyses were restricted to adults ≥18 years old. SWs completed a questionnaire and HIV/sexually transmitted infection testing. Using multivariate logistic regression, we identified associations with early sex work initiation (prostitution arrests among adult SWs. Of 508 SWs, 193 (38.0%) reported early sex work initiation, with 78.53% primarily street-involved SWs and 21.46% off-street SWs. HIV prevalence was 11.22%, which was 19.69% among early initiates. Early initiates were more likely to be Canadian born [adjusted odds ratio (AOR): 6.8, 95% confidence interval (CI): 2.42 to 19.02], inject drugs (AOR: 1.6, 95% CI: 1.0 to 2.5), and to have worked for a manager (AOR: 2.22, 95% CI: 1.3 to 3.6) or been coerced into sex work (AOR: 2.3, 95% CI: 1.14 to 4.44). Early initiation retained an independent effect on increased risk of HIV infection (AOR: 2.5, 95% CI: 1.3 to 3.2) and prostitution arrests (AOR: 2.0, 95% CI: 1.3 to 3.2). Adolescent sex work initiation is concentrated among marginalized, drug, and street-involved SWs. Early initiation holds an independent increased effect on HIV infection and criminalization of adult SWs. Findings suggest the need for evidence-based approaches to reduce harm among adult and youth SWs.
Brief Report: Translation and Adaptation of the Theory of Mind Inventory to Spanish

Science.gov (United States)

Pujals, Elena; Batlle, Santiago; Camprodon, Ester; Pujals, Sílvia; Estrada, Xavier; Aceña, Marta; Petrizan, Araitz; Duñó, Lurdes; Martí, Josep; Martin, Luis Miguel; Pérez-Solá, Víctor

2016-01-01

The Theory of Mind Inventory is an informant measure designed to evaluate children's theory of mind competence. We describe the translation and cultural adaptation of the inventory by the following process: (1) translation from English to Spanish by two independent certified translators; (2) production of an agreed version by a multidisciplinary…
FRC translation into a compression coil

International Nuclear Information System (INIS)

Chrien, R.E.

1985-01-01

Several features of the problem of FRC translation into a compression coil are considered. First, the magnitude of the guide field is calculated and found to exceed that which would be applied to a flux conserver. Second, energy conservation is applied to FRC translation from a flux conserver into a compression coil. It is found that a significant temperature decrease is required for translation to be energetically possible. The temperature change depends on the external inductance in the compression circuit. An analogous case is that of a compression region composed of a compound magnet; in this case the temperature change depends on the ratio of inner and outer coil radii. Finally, the kinematics of intermediate translation states are calculated using an ''abrupt transition'' model. It is found, in this model, that the FRC must overcome a potential hill during translation, which requires a small initial velocity
Translation Theory 'Translated'

DEFF Research Database (Denmark)

Wæraas, Arild; Nielsen, Jeppe

2016-01-01

Translation theory has proved to be a versatile analytical lens used by scholars working from different traditions. On the basis of a systematic literature review, this study adds to our understanding of the ‘translations’ of translation theory by identifying the distinguishing features of the most...... common theoretical approaches to translation within the organization and management discipline: actor-network theory, knowledge-based theory, and Scandinavian institutionalism. Although each of these approaches already has borne much fruit in research, the literature is diverse and somewhat fragmented......, but also overlapping. We discuss the ways in which the three versions of translation theory may be combined and enrich each other so as to inform future research, thereby offering a more complete understanding of translation in and across organizational settings....
Binary translation using peephole translation rules

Science.gov (United States)

Bansal, Sorav; Aiken, Alex

2010-05-04

An efficient binary translator uses peephole translation rules to directly translate executable code from one instruction set to another. In a preferred embodiment, the translation rules are generated using superoptimization techniques that enable the translator to automatically learn translation rules for translating code from the source to target instruction set architecture.
4EBP-Dependent Signaling Supports West Nile Virus Growth and Protein Expression.

Science.gov (United States)

Shives, Katherine D; Massey, Aaron R; May, Nicholas A; Morrison, Thomas E; Beckham, J David

2016-10-18

West Nile virus (WNV) is a (+) sense, single-stranded RNA virus in the Flavivirus genus. WNV RNA possesses an m7 GpppN m 5' cap with 2'- O -methylation that mimics host mRNAs preventing innate immune detection and allowing the virus to translate its RNA genome through the utilization of cap-dependent translation initiation effectors in a wide variety of host species. Our prior work established the requirement of the host mammalian target of rapamycin complex 1 (mTORC1) for optimal WNV growth and protein expression; yet, the roles of the downstream effectors of mTORC1 in WNV translation are unknown. In this study, we utilize gene deletion mutants in the ribosomal protein kinase called S6 kinase (S6K) and eukaryotic translation initiation factor 4E-binding protein (4EBP) pathways downstream of mTORC1 to define the role of mTOR-dependent translation initiation signals in WNV gene expression and growth. We now show that WNV growth and protein expression are dependent on mTORC1 mediated-regulation of the eukaryotic translation initiation factor 4E-binding protein/eukaryotic translation initiation factor 4E-binding protein (4EBP/eIF4E) interaction and eukaryotic initiation factor 4F (eIF4F) complex formation to support viral growth and viral protein expression. We also show that the canonical signals of mTORC1 activation including ribosomal protein s6 (rpS6) and S6K phosphorylation are not required for WNV growth in these same conditions. Our data suggest that the mTORC1/4EBP/eIF4E signaling axis is activated to support the translation of the WNV genome.
4EBP-Dependent Signaling Supports West Nile Virus Growth and Protein Expression

Directory of Open Access Journals (Sweden)

Katherine D. Shives

2016-10-01

Full Text Available West Nile virus (WNV is a (+ sense, single-stranded RNA virus in the Flavivirus genus. WNV RNA possesses an m7GpppNm 5′ cap with 2′-O-methylation that mimics host mRNAs preventing innate immune detection and allowing the virus to translate its RNA genome through the utilization of cap-dependent translation initiation effectors in a wide variety of host species. Our prior work established the requirement of the host mammalian target of rapamycin complex 1 (mTORC1 for optimal WNV growth and protein expression; yet, the roles of the downstream effectors of mTORC1 in WNV translation are unknown. In this study, we utilize gene deletion mutants in the ribosomal protein kinase called S6 kinase (S6K and eukaryotic translation initiation factor 4E-binding protein (4EBP pathways downstream of mTORC1 to define the role of mTOR-dependent translation initiation signals in WNV gene expression and growth. We now show that WNV growth and protein expression are dependent on mTORC1 mediated-regulation of the eukaryotic translation initiation factor 4E-binding protein/eukaryotic translation initiation factor 4E-binding protein (4EBP/eIF4E interaction and eukaryotic initiation factor 4F (eIF4F complex formation to support viral growth and viral protein expression. We also show that the canonical signals of mTORC1 activation including ribosomal protein s6 (rpS6 and S6K phosphorylation are not required for WNV growth in these same conditions. Our data suggest that the mTORC1/4EBP/eIF4E signaling axis is activated to support the translation of the WNV genome.
Labeling of eukaryotic messenger RNA 5' terminus with phosphorus -32: use of tobacco acid pyrophosphatase for removal of cap structures

International Nuclear Information System (INIS)

Lockard, R.E.; Rieser, L.; Vournakis, J.N.

1981-01-01

In recent years, there has been a growing appreciation of the potential applications of 5'- 32 P-end-labeled mRNA, not only for screening recombinant clones and mapping gene structure, but also for revealing possible nucleotide sequence and structural signals within mRNA molecules themselves, which may be important for eukaryotic mRNA processing and turnover and for controlling differential rates of translational initiation. Three major problems, however, have retarded progress in this area, lack of methods for efficient and reproducible removal of m7G5ppp5'-cap structures, which maintain the integrity of an RNA molecule; inability to generate a sufficient amount of labeled mRNA, owing to the limited availability of most pure mRNA species; and the frequent problem of RNA degradation during in vitro end-labeling owing to RNAse contamination. The procedures presented here permit one to decap and label minute quantities of mRNA, effectively. Tobacco acid pyrophosphatase is relatively efficient in removing cap structures from even nanogram quantities of available mRNA, and enough radioactivity can be easily generated from minute amounts ofintact mRNA with very high-specific-activity [gamma- 32 P]ATP and the inhibition of ribonuclease contamination with diethylpyrocarbonate. These procedures can be modified and applied to almost any other type of RNA molecule as well. In Section III of this volume, we explore in detail how effectively 5'-end-labeled mRNA can be used not only for nucleotide sequence analysis, but also for mapping mRNA secondary structure

5′-Phospho-RNA Acceptor Specificity of GDP Polyribonucleotidyltransferase of Vesicular Stomatitis Virus in mRNA Capping

Science.gov (United States)

Ogino, Minako

2017-01-01

ABSTRACT The GDP polyribonucleotidyltransferase (PRNTase) domain of the multifunctional L protein of rhabdoviruses, such as vesicular stomatitis virus (VSV) and rabies virus, catalyzes the transfer of 5′-phospho-RNA (pRNA) from 5′-triphospho-RNA (pppRNA) to GDP via a covalent enzyme-pRNA intermediate to generate a 5′-cap structure (GpppA). Here, using an improved oligo-RNA capping assay with the VSV L protein, we showed that the Michaelis constants for GDP and pppAACAG (VSV mRNA-start sequence) are 0.03 and 0.4 μM, respectively. A competition assay between GDP and GDP analogues in the GpppA formation and pRNA transfer assay using GDP analogues as pRNA acceptors indicated that the PRNTase domain recognizes the C-2-amino group, but not the C-6-oxo group, N-1-hydrogen, or N-7-nitrogen, of GDP for the cap formation. 2,6-Diaminopurine-riboside (DAP), 7-deazaguanosine (7-deaza-G), and 7-methylguanosine (m7G) diphosphates efficiently accepted pRNA, resulting in the formation of DAPpppA, 7-deaza-GpppA, and m7GpppA (cap 0), respectively. Furthermore, either the 2′- or 3′-hydroxyl group of GDP was found to be required for efficient pRNA transfer. A 5′-diphosphate form of antiviral ribavirin weakly inhibited the GpppA formation but did not act as a pRNA acceptor. These results indicate that the PRNTase domain has a unique guanosine-binding mode different from that of eukaryotic mRNA capping enzyme, guanylyltransferase. IMPORTANCE mRNAs of nonsegmented negative-strand (NNS) RNA viruses, such as VSV, possess a fully methylated cap structure, which is required for mRNA stability, efficient translation, and evasion of antiviral innate immunity in host cells. GDP polyribonucleotidyltransferase (PRNTase) is an unconventional mRNA capping enzyme of NNS RNA viruses that is distinct from the eukaryotic mRNA capping enzyme, guanylyltransferase. In this study, we studied the pRNA acceptor specificity of VSV PRNTase using various GDP analogues and identified chemical groups
Assessing excellence in translational cancer research: a consensus based framework.

Science.gov (United States)

Rajan, Abinaya; Caldas, Carlos; van Luenen, Henri; Saghatchian, Mahasti; van Harten, Wim H

2013-10-29

It takes several years on average to translate basic research findings into clinical research and eventually deliver patient benefits. An expert-based excellence assessment can help improve this process by: identifying high performing Comprehensive Cancer Centres; best practices in translational cancer research; improving the quality and efficiency of the translational cancer research process. This can help build networks of excellent Centres by aiding focused partnerships. In this paper we report on a consensus building exercise that was undertaken to construct an excellence assessment framework for translational cancer research in Europe. We used mixed methods to reach consensus: a systematic review of existing translational research models critically appraised for suitability in performance assessment of Cancer Centres; a survey among European stakeholders (researchers, clinicians, patient representatives and managers) to score a list of potential excellence criteria, a focus group with selected representatives of survey participants to review and rescore the excellence criteria; an expert group meeting to refine the list; an open validation round with stakeholders and a critical review of the emerging framework by an independent body: a committee formed by the European Academy of Cancer Sciences. The resulting excellence assessment framework has 18 criteria categorized in 6 themes. Each criterion has a number of questions/sub-criteria. Stakeholders favoured using qualitative excellence criteria to evaluate the translational research "process" rather than quantitative criteria or judging only the outputs. Examples of criteria include checking if the Centre has mechanisms that can be rated as excellent for: involvement of basic researchers and clinicians in translational research (quality of supervision and incentives provided to clinicians to do a PhD in translational research) and well designed clinical trials based on ground-breaking concepts (innovative
Determination of the Ca/P ratio in calcium phosphates during the precipitation of hydroxyapatite using X-ray diffractometry

Directory of Open Access Journals (Sweden)

Zoltan Z. Zyman

2013-06-01

Full Text Available The applicability of the X-ray powder diffraction method to the determination of phase composition and Ca/P ratio in precipitates during the nitrous wet synthesis of hydroxyapatite (HA has been shown. The plotted dependences of the phase composition and the Ca/P ratio on the synthesis time can be used as initial data for the development of new and simple processing routes of calcium phosphate ceramics based on HA of any desired composition.
The comparison of CAP88-PC version 2.0 versus CAP88-PC version 1.0

International Nuclear Information System (INIS)

Yakubovich, B.A.; Klee, K.O.; Palmer, C.R.; Spotts, P.B.

1997-12-01

40 CFR Part 61 (Subpart H of the NESHAP) requires DOE facilities to use approved sampling procedures, computer models, or other approved procedures when calculating Effective Dose Equivalent (EDE) values to members of the public. Currently version 1.0 of the approved computer model CAP88-PC is used to calculate EDE values. The DOE has upgraded the CAP88-PC software to version 2.0. This version provides simplified data entry, better printing characteristics, the use of a mouse, and other features. The DOE has developed and released version 2.0 for testing and comment. This new software is a WINDOWS based application that offers a new graphical user interface with new utilities for preparing and managing population and weather data, and several new decay chains. The program also allows the user to view results before printing. This document describes a test that confirmed CAP88-PC version 2.0 generates results comparable to the original version of the CAP88-PC program
Translating Research into Classroom Practice: Workplace Independence for Students with Severe Handicaps.

Science.gov (United States)

Hughes, Carolyn; And Others

1989-01-01

The article describes a process for use in high-school transition programs to promote student independence within the context of vocational training. Strategies described include: evaluating student independence in community-based settings, teaching student adaptability, and transferring control of student independence to work-related stimuli. A…
Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats

Directory of Open Access Journals (Sweden)

Mello Maria

2007-03-01

Full Text Available Abstract Background Cancer-cachexia induces a variety of metabolic disorders on protein turnorver, decreasing protein synthesis and increasing protein degradation. Controversly, insulin, other hormones, and branched-chain amino acids, especially leucine, stimulate protein synthesis and modulate the activity of translation initiation factors involved in protein synthesis. Since the tumour effects are more pronounced when associated with pregnancy, ehancing muscle-wasting proteolysis, in this study, the influence of a leucine-rich diet on the protein synthesis caused by cancer were investigated. Methods Pregnant rats with or without Walker 256 tumour were distributed into six groups. During 20 days of experiment, three groups were fed with a control diet: C – pregnant control, W – tumour-bearing, and P – pair-fed, which received the same amount of food as ingested by the W group; three other groups of pregnant rats were fed a leucine-rich diet: L – pregnant leucine, WL – tumour-bearing, and PL – pair-fed, which received the same amount of food as ingested by the WL group. Results The gastrocnemius muscle of WL rats showed increased incorporation of leucine in protein compared to W rats; the leucine-rich diet also prevented the decrease in plasma insulin normally seen in W. The expression of translation initiation factors increased when tumour-bearing rats fed leucine-rich diet, with increase of ~35% for eIF2α and eIF5, ~17% for eIF4E and 20% for eIF4G; the expression of protein kinase S6K1 and protein kinase C was also highly enhanced. Conclusion The results suggest that a leucine-rich diet increased the protein synthesis in skeletal muscle in tumour-bearing rats possibly through the activation of eIF factors and/or the S6kinase pathway.
Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats

International Nuclear Information System (INIS)

Ventrucci, Gislaine; Mello, Maria Alice R; Gomes-Marcondes, Maria Cristina C

2007-01-01

Cancer-cachexia induces a variety of metabolic disorders on protein turnorver, decreasing protein synthesis and increasing protein degradation. Controversly, insulin, other hormones, and branched-chain amino acids, especially leucine, stimulate protein synthesis and modulate the activity of translation initiation factors involved in protein synthesis. Since the tumour effects are more pronounced when associated with pregnancy, ehancing muscle-wasting proteolysis, in this study, the influence of a leucine-rich diet on the protein synthesis caused by cancer were investigated. Pregnant rats with or without Walker 256 tumour were distributed into six groups. During 20 days of experiment, three groups were fed with a control diet: C – pregnant control, W – tumour-bearing, and P – pair-fed, which received the same amount of food as ingested by the W group; three other groups of pregnant rats were fed a leucine-rich diet: L – pregnant leucine, WL – tumour-bearing, and PL – pair-fed, which received the same amount of food as ingested by the WL group. The gastrocnemius muscle of WL rats showed increased incorporation of leucine in protein compared to W rats; the leucine-rich diet also prevented the decrease in plasma insulin normally seen in W. The expression of translation initiation factors increased when tumour-bearing rats fed leucine-rich diet, with increase of ~35% for eIF2α and eIF5, ~17% for eIF4E and 20% for eIF4G; the expression of protein kinase S6K1 and protein kinase C was also highly enhanced. The results suggest that a leucine-rich diet increased the protein synthesis in skeletal muscle in tumour-bearing rats possibly through the activation of eIF factors and/or the S6kinase pathway
Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats

Energy Technology Data Exchange (ETDEWEB)

Ventrucci, Gislaine [Laboratório de Nutrição e Câncer, Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, 13083-970, São Paulo (Brazil); Mello, Maria Alice R [Departamento de Fisiologia e Biofísica, Instituto Biociências, Universidade Estadual de São Paulo, UNESP, Rio Claro, 13506-900, São Paulo (Brazil); Gomes-Marcondes, Maria Cristina C [Laboratório de Nutrição e Câncer, Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, 13083-970, São Paulo (Brazil)

2007-03-06

Cancer-cachexia induces a variety of metabolic disorders on protein turnorver, decreasing protein synthesis and increasing protein degradation. Controversly, insulin, other hormones, and branched-chain amino acids, especially leucine, stimulate protein synthesis and modulate the activity of translation initiation factors involved in protein synthesis. Since the tumour effects are more pronounced when associated with pregnancy, ehancing muscle-wasting proteolysis, in this study, the influence of a leucine-rich diet on the protein synthesis caused by cancer were investigated. Pregnant rats with or without Walker 256 tumour were distributed into six groups. During 20 days of experiment, three groups were fed with a control diet: C – pregnant control, W – tumour-bearing, and P – pair-fed, which received the same amount of food as ingested by the W group; three other groups of pregnant rats were fed a leucine-rich diet: L – pregnant leucine, WL – tumour-bearing, and PL – pair-fed, which received the same amount of food as ingested by the WL group. The gastrocnemius muscle of WL rats showed increased incorporation of leucine in protein compared to W rats; the leucine-rich diet also prevented the decrease in plasma insulin normally seen in W. The expression of translation initiation factors increased when tumour-bearing rats fed leucine-rich diet, with increase of ~35% for eIF2α and eIF5, ~17% for eIF4E and 20% for eIF4G; the expression of protein kinase S6K1 and protein kinase C was also highly enhanced. The results suggest that a leucine-rich diet increased the protein synthesis in skeletal muscle in tumour-bearing rats possibly through the activation of eIF factors and/or the S6kinase pathway.
FRC translation into a compression coil

International Nuclear Information System (INIS)

Chrien, R.E.

1986-01-01

The equilibrium and translational kinematics of Field-Reversed Configurations (FRCs) in a cylindrical coil which does not conserve flux are problems that arise in connection with adiabatic compressional heating. In this paper, they consider several features of the problem of FRC translation into a compression coil. First, the magnitude of the guide field is calculated and found to exceed that which would be applied to a flux conserver. Second, energy conservation is applied to FRC translation from a flux conserver into a compression coil. It is found that a significant temperature decrease is required for translation to be energetically possible. The temperature change depends on the external inductance in the compression circuit. An analogous case is that of a compression region composed of a compound magnet; in this case the temperature change depends on the ratio of inner and outer coil radii. Finally, the kinematics of intermediate translation states are calculated using an abrupt transition model. It is found, in this model, that the FRC must overcome a potential hill during translation, which requires a small initial velocity
Blasting agents and initiation systems

Energy Technology Data Exchange (ETDEWEB)

Fiscor, S.

2000-01-01

Although blasting differs between and within each industry, as a whole, the mines and quarries are making a shift from a purely ammonium nitrate/fuel oil (ANFO) mixture to a blend of emulsion and ANFO on a straight emulsion. Non-electric (shock tube) initiation systems have provided a viable alternative to the electric detonator (blasting cap). Explosives manufacturers are seeing their roles changes to being blasting contractors or consultants rather than just suppliers. The article discusses these trends and gives examples of typical blasting techniques and amounts of blasting agent used at large USA surface coal mines. Electric caps are still used in blasting underground coal. The Ensign Bickford Co. (EBCo) is developing electronic detonators and has been field testing an electronic initiator, the DIGIDET detonator, for the last four years. When commercially available, electronic detonators will be accurate but will come with a hefty price tag. 2 photos.
A universal trend of reduced mRNA stability near the translation-initiation site in prokaryotes and eukaryotes.

Directory of Open Access Journals (Sweden)

Wanjun Gu

2010-02-01

Full Text Available Recent studies have suggested that the thermodynamic stability of mRNA secondary structure near the start codon can regulate translation efficiency in Escherichia coli, and that translation is more efficient the less stable the secondary structure. We survey the complete genomes of 340 species for signals of reduced mRNA secondary structure near the start codon. Our analysis includes bacteria, archaea, fungi, plants, insects, fishes, birds, and mammals. We find that nearly all species show evidence for reduced mRNA stability near the start codon. The reduction in stability generally increases with increasing genomic GC content. In prokaryotes, the reduction also increases with decreasing optimal growth temperature. Within genomes, there is variation in the stability among genes, and this variation correlates with gene GC content, codon bias, and gene expression level. For birds and mammals, however, we do not find a genome-wide trend of reduced mRNA stability near the start codon. Yet the most GC rich genes in these organisms do show such a signal. We conclude that reduced stability of the mRNA secondary structure near the start codon is a universal feature of all cellular life. We suggest that the origin of this reduction is selection for efficient recognition of the start codon by initiator-tRNA.
Death cap

DEFF Research Database (Denmark)

Rudbæk, Torsten R; Kofoed, Pernille Bouteloup; Bove, Jeppe

2014-01-01

Death cap (Amanita phalloides) is commonly found and is one of the five most toxic fungi in Denmark. Toxicity is due to amatoxin, and poisoning is a serious medical condition, causing organ failure with potential fatal outcome. Acknowledgement and clarification of exposure, symptomatic and focused...
Early sex work initiation independently elevates odds of HIV infection and police arrest among adult sex workers in a Canadian setting

Science.gov (United States)

GOLDENBERG, Shira M.; CHETTIAR, Jill; SIMO, Annick; SILVERMAN, Jay G.; STRATHDEE, Steffanie A.; MONTANER, Julio; SHANNON, Kate

2014-01-01

Objectives To explore factors associated with early sex work initiation, and model the independent effect of early initiation on HIV infection and prostitution arrests among adult sex workers (SWs). Design Baseline data (2010–2011) were drawn from a cohort of SWs who exchanged sex for money within the last month and were recruited through time-location sampling in Vancouver, Canada. Analyses were restricted to adults ≥18 years old. Methods SWs completed a questionnaire and HIV/STI testing. Using multivariate logistic regression, we identified associations with early sex work initiation (prostitution arrests among adult SWs. Results Of 508 SWs, 193 (38.0%) reported early sex work initiation, with 78.53% primarily street-involved SWs and 21.46% off-street SWs. HIV prevalence was 11.22%, which was 19.69% among early initiates. Early initiates were more likely to be Canadian-born (Adjusted Odds Ratio (AOR): 6.8, 95% Confidence Interval (CI): 2.42–19.02), inject drugs (AOR: 1.6, 95%CI: 1.0–2.5), and to have worked for a manager (AOR: 2.22, 95%CI: 1.3–3.6) or been coerced into sex work (AOR: 2.3, 95%CI: 1.14–4.44). Early initiation retained an independent effect on increased risk of HIV infection (AOR: 2.5, 95% CI: 1.3–3.2) and prostitution arrests (AOR: 2.0, 95%CI: 1.3–3.2). Conclusions Adolescent sex work initiation is concentrated among marginalized, drug and street-involved SWs. Early initiation holds an independent increased effect on HIV infection and criminalization of adult SWs. Findings suggest the need for evidence-based approaches to reduce harm among adult and youth SWs. PMID:23982660
Divergent picornavirus IRES elements

DEFF Research Database (Denmark)

Belsham, Graham

2009-01-01

Internal ribosome entry site (IRES) elements were first identified about 20 years ago within the 5' untranslated region of picornavirus RNAs. They direct a cap-independent mechanism of translation initiation on the viral RNA. Within the picornavirus family it is now known that there are four...... classes of IRES element which vary in size (450-270nt), they also have different, complex, secondary structures and distinct requirements for cellular proteins to allow them to function. This review describes the features of each class of picornavirus IRES element but focuses on the characteristics...... of the most recently described group, initially identified within the porcine teschovirus-1 RNA, which has strong similarities to the IRES elements from within the genomes of hepatitis C virus and the pestiviruses which are members of the flavivirus family. The selection of the initiation codon...
Oversight role of the Independent Monitoring Board of the Global Polio Eradication Initiative.

Science.gov (United States)

Rutter, Paul D; Donaldson, Liam J

2014-11-01

The Global Polio Eradication Initiative (GPEI) established its Independent Monitoring Board (IMB) in 2010 to monitor and guide its progress toward stopping polio transmission globally. The concept of an IMB is innovative, with no clear analogue in the history of the GPEI or in any other global health program. The IMB meets with senior program officials every 3-6 months. Its reports provide analysis and recommendations about individual polio-affected countries. The IMB also examines issues affecting the global program as a whole. Its areas of focus have included escalating the level of priority afforded to polio eradication (particularly by recommending a World Health Assembly resolution to declare polio eradication a programmatic emergency, which was enacted in May 2012), placing greater emphasis on people factors in the delivery of the program, encouraging innovation, strengthening focus on the small number of so-called sanctuaries where polio persists, and continuous quality improvement to reach every missed child with vaccination. The IMB's true independence from the agencies and countries delivering the program has enabled it to raise difficult issues that others cannot. Other global health programs might benefit from establishing similar independent monitoring mechanisms. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Netrin-1 Protects Hepatocytes Against Cell Death Through Sustained Translation During the Unfolded Protein ResponseSummary

Directory of Open Access Journals (Sweden)

Thomas Lahlali

2016-05-01

Full Text Available Background & Aims: Netrin-1, a multifunctional secreted protein, is up-regulated in cancer and inflammation. Netrin-1 blocks apoptosis induced by the prototypical dependence receptorsÂ deleted in colorectal carcinoma and uncoordinated phenotype-5. Although the unfolded protein response (UPR triggers apoptosis on exposure to stress, it first attempts to restore endoplasmic reticulum homeostasis to foster cell survival. Importantly, UPR is implicated in chronic liver conditions including hepatic oncogenesis. Netrin-1's implication in cell survival on UPR in this context is unknown. Methods: Isolation of translational complexes, determination of RNA secondary structures by selective 2â-hydroxyl acylation and primer extension/dimethyl sulfate, bicistronic constructs, as well as conventional cell biology and biochemistry approachesÂ were used on inÂ vitroâgrown hepatocytic cells, wild-type, and netrin-1 transgenic mice. Results: HepaRG cells constitute a bona fide model for UPR studies inÂ vitro through adequate activation of the 3 sensors of the UPR (protein kinase RNAâlike endoplasmic reticulum kinase (PERK, inositol requiring enzyme 1Î± (IRE1Î±, and activated transcription factor 6 (ATF6. The netrin-1 messenger RNA 5'-end was shown to fold into a complex double pseudoknot and bear E-loop motifs, both of which are representative hallmarks of related internal ribosome entry site regions. Cap-independent translation of netrin 5' untranslated regionâdriven luciferase was observed on UPR inÂ vitro. Unlike several structurally related oncogenic transcripts (l-myc, c-myc, c-myb, netrin-1 messenger RNA was selected for translation during UPR both in human hepatocytes and in mice livers. Depletion of netrin-1 during UPR induces apoptosis, leading to cell death through an uncoordinated phenotype-5A/Câmediated involvement of protein phosphatase 2A and death-associated protein kinase 1 inÂ vitro and in netrin
The N-terminal region of eukaryotic translation initiation factor 5A signals to nuclear localization of the protein

International Nuclear Information System (INIS)

Parreiras-e-Silva, Lucas T.; Gomes, Marcelo D.; Oliveira, Eduardo B.; Costa-Neto, Claudio M.

2007-01-01

The eukaryotic translation initiation factor 5A (eIF5A) is a ubiquitous protein of eukaryotic and archaeal organisms which undergoes hypusination, a unique post-translational modification. We have generated a polyclonal antibody against murine eIF5A, which in immunocytochemical assays in B16-F10 cells revealed that the endogenous protein is preferentially localized to the nuclear region. We therefore analyzed possible structural features present in eIF5A proteins that could be responsible for that characteristic. Multiple sequence alignment analysis of eIF5A proteins from different eukaryotic and archaeal organisms showed that the former sequences have an extended N-terminal segment. We have then performed in silico prediction analyses and constructed different truncated forms of murine eIF5A to verify any possible role that the N-terminal extension might have in determining the subcellular localization of the eIF5A in eukaryotic organisms. Our results indicate that the N-terminal extension of the eukaryotic eIF5A contributes in signaling this protein to nuclear localization, despite of bearing no structural similarity with classical nuclear localization signals
Machine Translation and Other Translation Technologies.

Science.gov (United States)

Melby, Alan

1996-01-01

Examines the application of linguistic theory to machine translation and translator tools, discusses the use of machine translation and translator tools in the real world of translation, and addresses the impact of translation technology on conceptions of language and other issues. Findings indicate that the human mind is flexible and linguistic…
Enhancement of device performance by using quaternary capping over ternary capping in strain-coupled InAs/GaAs quantum dot infrared photodetectors

International Nuclear Information System (INIS)

Tongbram, B.; Shetty, S.; Ghadi, H.; Adhikary, S.; Chakrabarti, S.

2015-01-01

We investigate and compare the performance of 30 layers strain-coupled quantum dot (SCQD) infrared photodetectors capped with one of two different layers: a quaternary (In 0.21 Al 0.21 Ga 0.58 As) or ternary (In 0.15 Ga 0.85 As) alloy of 30 Aa and a GaAs layer with a thickness of 120-150 Aa. Measurements of optical properties, spectral responsivity, and cross-sectional transmission electron microscopy were conducted. Results showed that quaternary capping yielded more superior multilayer QD infrared photodetectors than ternary capping. Quaternary capping resulted in enhanced dot size, order, and uniformity of the QD array. The presence of Al in the capped layer helped in the reduction in dark current density and spectral linewidth as well as led to higher electron confinement of the QDs and enhanced device detectivity. The vertically ordered SCQD system with quaternary capping exhibited higher peak detectivity (∝10 10 cm Hz 1/2 /W) than that with ternary capping (∝10 7 cm Hz 1/2 /W). In addition, a very low noise current density of ∝10 -16 A/cm 2 Hz 1/2 at 77 K was achieved with quaternary-capped QDs. (orig.)
Direct visualization of redistribution and capping of fluorescent gangliosides on lymphocytes

OpenAIRE

1984-01-01

Fluorescent derivatives of gangliosides were prepared by oxidizing the sialyl residues to aldehydes and reacting them with fluorescent hydrazides. When rhodaminyl gangliosides were incubated with lymphocytes, the cells incorporated them in a time- and temperature- dependent manner. Initially, the gangliosides were evenly distributed on the cell surface but were redistributed into patches and caps by antirhodamine antibodies. When the cells were then stained with a second antibody or protein A...

Structural changes of eIF4E upon binding to the mRNA 5' monomethylguanosine and trimethylguanosine Cap.

Science.gov (United States)

Rutkowska-Wlodarczyk, Izabela; Stepinski, Janusz; Dadlez, Michal; Darzynkiewicz, Edward; Stolarski, Ryszard; Niedzwiecka, Anna

2008-03-04

Recognition of the 5' cap by the eukaryotic initiation factor 4E (eIF4E) is the rate-limiting step in the ribosome recruitment to mRNAs. The regular cap consists of 7-monomethylguanosine (MMG) linked by a 5'-5' triphosphate bridge to the first transcribed nucleoside, while some primitive eukaryotes possess a N (2), N (2),7-trimethylguanosine (TMG) cap structure as a result of trans splicing. Mammalian eIF4E is highly specific to the MMG form of the cap in terms of association constants and thermodynamic driving force. We have investigated conformational changes of eIF4E induced by interaction with two cap analogues, 7-methyl-GTP and N (2), N (2),7-trimethyl-GTP. Hydrogen-deuterium exchange and electrospray mass spectrometry were applied to probe local dynamics of murine eIF4E in the apo and cap-bound forms. The data show that the cap binding induces long-range conformational changes in the protein, not only in the cap-binding pocket but also in a distant region of the 4E-BP/eIF4G binding site. Formation of the complex with 7-methyl-GTP makes the eIF4E structure more compact, while binding of N (2), N (2),7-trimethyl-GTP leads to higher solvent accessibility of the protein backbone in comparison with the apo form. The results suggest that the additional double methylation at the N (2)-amino group of the cap causes sterical effects upon binding to mammalian eIF4E which influence the overall solution dynamics of the protein, thus precluding formation of a tight complex.
Apical cap

International Nuclear Information System (INIS)

McLoud, T.C.; Isler, R.J.; Novelline, R.A.; Putman, C.E.; Simeone, J.; Stark, P.

1981-01-01

Apical caps, either unilateral or bilateral, are a common feature of advancing age and are usually the result of subpleural scarring unassociated with other diseases. Pancoast (superior sulcus) tumors are a well recognized cause of unilateral asymmetric apical density. Other lesions arising in the lung, pleura, or extrapleural space may produce unilateral or bilateral apical caps. These include: (1) inflammatory: tuberculosis and extrapleural abscesses extending from the neck; (2) post radiation fibrosis after mantle therapy for Hodgkin disease or supraclavicular radiation in the treatment of breast carcinoma; (3) neoplasm: lymphoma extending from the neck or mediastinum, superior sulcus bronchogenic carcinoma, and metastases; (4) traumatic: extrapleural dissection of blood from a ruptured aorta, fractures of the ribs or spine, or hemorrhage due to subclavian line placement; (5) vascular: coarctation of the aorta with dilated collaterals over the apex, fistula between the subclavian artery and vein; and (6) miscellaneous: mediastinal lipomatosis with subcostal fat extending over the apices
PRMT1-Mediated Translation Regulation Is a Crucial Vulnerability of Cancer.

Science.gov (United States)

Hsu, Jessie Hao-Ru; Hubbell-Engler, Benjamin; Adelmant, Guillaume; Huang, Jialiang; Joyce, Cailin E; Vazquez, Francisca; Weir, Barbara A; Montgomery, Philip; Tsherniak, Aviad; Giacomelli, Andrew O; Perry, Jennifer A; Trowbridge, Jennifer; Fujiwara, Yuko; Cowley, Glenn S; Xie, Huafeng; Kim, Woojin; Novina, Carl D; Hahn, William C; Marto, Jarrod A; Orkin, Stuart H

2017-09-01

Through an shRNA screen, we identified the protein arginine methyltransferase Prmt1 as a vulnerable intervention point in murine p53/Rb-null osteosarcomas, the human counterpart of which lacks effective therapeutic options. Depletion of Prmt1 in p53-deficient cells impaired tumor initiation and maintenance in vitro and in vivo Mechanistic studies reveal that translation-associated pathways were enriched for Prmt1 downstream targets, implicating Prmt1 in translation control. In particular, loss of Prmt1 led to a decrease in arginine methylation of the translation initiation complex, thereby disrupting its assembly and inhibiting translation. p53/Rb-null cells were sensitive to p53-induced translation stress, and analysis of human cancer cell line data from Project Achilles further revealed that Prmt1 and translation-associated pathways converged on the same functional networks. We propose that targeted therapy against Prmt1 and its associated translation-related pathways offer a mechanistic rationale for treatment of osteosarcomas and other cancers that exhibit dependencies on translation stress response. Cancer Res; 77(17); 4613-25. ©2017 AACR . ©2017 American Association for Cancer Research.
47 CFR 61.41 - Price cap requirements generally.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Price cap requirements generally. 61.41 Section... (CONTINUED) TARIFFS General Rules for Dominant Carriers § 61.41 Price cap requirements generally. (a... companies shall not bar a carrier from electing price cap regulation provided the carrier is otherwise...
Translation of the shallot virus X TGB3 gene depends on non-AUG initiation and leaky scanning.

Science.gov (United States)

Lezzhov, Alexander A; Gushchin, Vladimir A; Lazareva, Ekaterina A; Vishnichenko, Valery K; Morozov, Sergey Y; Solovyev, Andrey G

2015-10-01

Triple gene block (TGB), a conserved gene module found in the genomes of many filamentous and rod-shaped plant viruses, encodes three proteins, TGB1, TGB2 and TGB3, required for viral cell-to-cell movement through plasmodesmata and systemic transport via the phloem. The genome of Shallot virus X, the type species of the genus Allexivirus, includes TGB1 and TGB2 genes, but contains no canonical ORF for TGB3 protein. However, a TGB3-like protein-encoding sequence lacking an AUG initiator codon has been found in the shallot virus X (ShVX) genome in a position typical for TGB3 genes. This putative TGB3 gene is conserved in all allexiviruses. Here, we carried out sequence analysis to predict possible non-AUG initiator codons in the ShVX TGB3-encoding sequence. We further used an agroinfiltration assay in Nicotiana benthamiana to confirm this prediction. Site-directed mutagenesis was used to demonstrate that the ShVX TGB3 could be translated on a bicistronic mRNA template via a leaky scanning mechanism.
30 CFR 250.1157 - How do I receive approval to produce gas-cap gas from an oil reservoir with an associated gas cap?

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false How do I receive approval to produce gas-cap gas from an oil reservoir with an associated gas cap? 250.1157 Section 250.1157 Mineral Resources... do I receive approval to produce gas-cap gas from an oil reservoir with an associated gas cap? (a...
Devon island ice cap: core stratigraphy and paleoclimate.

Science.gov (United States)

Koerner, R M

1977-04-01

Valuable paleoclimatic information can be gained by studying the distribution of melt layers in deep ice cores. A profile representing the percentage of ice in melt layers in a core drilled from the Devon Island ice cap plotted against both time and depth shows that the ice cap has experienced a period of very warm summers since 1925, following a period of colder summers between about 1600 and 1925. The earlier period was coldest between 1680 and 1730. There is a high correlation between the melt-layer ice percentage and the mass balance of the ice cap. The relation between them suggests that the ice cap mass balance was zero (accumulation equaled ablation) during the colder period but is negative in the present warmer one. There is no firm evidence of a present cooling trend in the summer conditions on the ice cap. A comparison with the melt-layer ice percentage in cores from the other major Canadian Arctic ice caps shows that the variation of summer conditions found for the Devon Island ice cap is representative for all the large ice caps for about 90 percent of the time. There is also a good correlation between melt-layer percentage and summer sea-ice conditions in the archipelago. This suggests that the search for the northwest passage was influenced by changing climate, with the 19th-century peak of the often tragic exploration coinciding with a period of very cold summers.
The tRNA-like structure of Turnip yellow mosaic virus RNA is a 3'-translational enhancer

International Nuclear Information System (INIS)

Matsuda, Daiki; Dreher, Theo W.

2004-01-01

Many positive stand RNA viral genomes lack the poly(A) tail that is characteristic of cellular mRNAs and that promotes translation in cis. The 3' untranslated regions (UTRs) of such genomes are expected to provide similar translation-enhancing properties as a poly(A) tail, yet the great variety of 3' sequences suggests that this is accomplished in a range of ways. We have identified a translational enhancer present in the 3' UTR of Turnip yellow mosaic virus (TYMV) RNA using luciferase reporter RNAs with generic 5' sequences transfected into plant cells. The 3' terminal 109 nucleotides comprising the tRNA-like structure (TLS) and an upstream pseudoknot (UPSK) act in synergy with a 5'-cap to enhance translation, with a minor contribution in stabilizing the RNA. Maximum enhancement requires that the RNA be capable of aminoacylation, but either the native valine or engineered methionine is acceptable. Mutations that decrease the affinity for translation elongation factor eEF1A (but also diminish aminoacylation efficiency) strongly decrease translational enhancement, suggesting that eEF1A is mechanistically involved. The UPSK seems to act as an important, though nonspecific, spacer element ensuring proper presentation of a functional TLS. Our studies have uncovered a novel type of translational enhancer and a new role for a plant viral TLS
Leaderless Transcripts and Small Proteins Are Common Features of the Mycobacterial Translational Landscape.

Directory of Open Access Journals (Sweden)

Scarlet S Shell

2015-11-01

Full Text Available RNA-seq technologies have provided significant insight into the transcription networks of mycobacteria. However, such studies provide no definitive information on the translational landscape. Here, we use a combination of high-throughput transcriptome and proteome-profiling approaches to more rigorously understand protein expression in two mycobacterial species. RNA-seq and ribosome profiling in Mycobacterium smegmatis, and transcription start site (TSS mapping and N-terminal peptide mass spectrometry in Mycobacterium tuberculosis, provide complementary, empirical datasets to examine the congruence of transcription and translation in the Mycobacterium genus. We find that nearly one-quarter of mycobacterial transcripts are leaderless, lacking a 5' untranslated region (UTR and Shine-Dalgarno ribosome-binding site. Our data indicate that leaderless translation is a major feature of mycobacterial genomes and is comparably robust to leadered initiation. Using translational reporters to systematically probe the cis-sequence requirements of leaderless translation initiation in mycobacteria, we find that an ATG or GTG at the mRNA 5' end is both necessary and sufficient. This criterion, together with our ribosome occupancy data, suggests that mycobacteria encode hundreds of small, unannotated proteins at the 5' ends of transcripts. The conservation of small proteins in both mycobacterial species tested suggests that some play important roles in mycobacterial physiology. Our translational-reporter system further indicates that mycobacterial leadered translation initiation requires a Shine Dalgarno site in the 5' UTR and that ATG, GTG, TTG, and ATT codons can robustly initiate translation. Our combined approaches provide the first comprehensive view of mycobacterial gene structures and their non-canonical mechanisms of protein expression.
Translational control in plant antiviral immunity

Directory of Open Access Journals (Sweden)

João Paulo B. Machado

Full Text Available Abstract Due to the limited coding capacity of viral genomes, plant viruses depend extensively on the host cell machinery to support the viral life cycle and, thereby, interact with a large number of host proteins during infection. Within this context, as plant viruses do not harbor translation-required components, they have developed several strategies to subvert the host protein synthesis machinery to produce rapidly and efficiently the viral proteins. As a countermeasure against infection, plants have evolved defense mechanisms that impair viral infections. Among them, the host-mediated translational suppression has been characterized as an efficient mean to restrict infection. To specifically suppress translation of viral mRNAs, plants can deploy susceptible recessive resistance genes, which encode translation initiation factors from the eIF4E and eIF4G family and are required for viral mRNA translation and multiplication. Additionally, recent evidence has demonstrated that, alternatively to the cleavage of viral RNA targets, host cells can suppress viral protein translation to silence viral RNA. Finally, a novel strategy of plant antiviral defense based on suppression of host global translation, which is mediated by the transmembrane immune receptor NIK1 (nuclear shuttle protein (NSP-Interacting Kinase1, is discussed in this review.
CAP FUTURE: WHAT DO STAKEHOLDERS WANT?

Directory of Open Access Journals (Sweden)

Petr BLIZKOVSKY

2018-03-01

Full Text Available The Common Agricultural Policy (CAP is at the crossroads of several policy interests. It is scrutinised by farming and environmental communities as well as by the food industry, regional authorities, research and public sector. The paper analyses the recent consultation process undertaken by the European Commission. The paper concludes that among the key reform issues are: the level of the financial support to the CAP; the continued environmental and other public goods orientation of the CAP and generational renewal. In addition, the focus on result orientation and reduction of the administrative burden can be expected. The relevant European Commission proposals are foreseen around summer 2018.
Empiric penicillin monotherapy of CAP is not associated with increased mortality; experiences from the retrospective CAP-North cohort

DEFF Research Database (Denmark)

Baunbæk-Knudsen, Getrud; Vestergaard Jensen, Andreas; Andersen, Stine

2016-01-01

Background: Community-acquired pneumonia (CAP) is a severe infection, with high morbidity and mortality. The antibiotic strategies for CAP differ across Europe. Objective: To assess the usage of Penicillin monotherapy in a real-life cohort and to evaluate predictors of treatment duration and the ......Background: Community-acquired pneumonia (CAP) is a severe infection, with high morbidity and mortality. The antibiotic strategies for CAP differ across Europe. Objective: To assess the usage of Penicillin monotherapy in a real-life cohort and to evaluate predictors of treatment duration......, and evaluated predictors of treatment duration by linear regression. Mortality of patients receiving empiric penicillin-G/V was compared to others by logistic regression analysis. The CAPNETZ database technology was used for data-capture. Results: We included 1320 patients. The incidence of hospitalized CAP...... was 3.1 per 1000 inhabitants. The median age was 71 years (IQR; 58.81). In-hospital mortality was 8%. Patients treated with penicillin-G/V as empiric monotherapy (45%) did not have a higher mortality than those treated with broader spectrum antibiotics (OR 1.30, CI 95% 0.84-2-02). The median duration...
A Duopoly Manufacturers’ Game Model Considering Green Technology Investment under a Cap-and-Trade System

Directory of Open Access Journals (Sweden)

Yi Zheng

2018-03-01

Full Text Available This research studied the duopoly manufacturers’ decision-making considering green technology investment and under a cap-and-trade system. It was assumed there were two manufacturers producing products which were substitutable for one another. On the basis of this assumption, the optimal production capacity, price, and green technology investment of the duopoly manufacturers under a cap-and-trade system were obtained. The increase or decrease of the optimal production quantity of the duopoly manufacturers under a cap-and-trade system was decided by their green technology level. The increase of the optimal price as well as the increase or decrease of the maximum expected profits were decided by the initial carbon emission quota granted by the government. Our research indicates that the carbon emission of unit product is inversely proportional to the market share of an enterprise and becomes an important index to measure the core competitiveness of an enterprise.
Progress in LAr EndCap Calorimetry: News from the Hadronic EndCap Group.

CERN Multimedia

Oram, C.J.

With module production and testing completed for the Hadronic EndCap calorimeter, the attention of the HEC group is heavily directed towards wheel assembly in building 180. Three of the four HEC wheels are now assembled and rotated, and work is progressing on assembling the final wheel. This year has been a busy year for the installation of components in the EndCap C cryostat: the signal feedthrough installation was completed April 22nd, the pre-sampler shortly thereafter and the Electro-Magnetic EndCap August 13th. This allowed the HEC group to start transferring the HEC wheels from the T6A storage cradle into the cryostat. The operation started in mid-September and has progressed, on or ahead of schedule, since then with the major milestones being: Insertion of 67 ton front HEC wheel October 3rd Insertion of 90 ton rear HEC wheel October 22nd. The wheel alignment has proved to be excellent, with the position of the centre of the front(rear) wheel with respect to the nominal position being displaced b...
The Drosophila PNG kinase complex regulates the translation of cyclin B.

Science.gov (United States)

Vardy, Leah; Orr-Weaver, Terry L

2007-01-01

The Drosophila PAN GU (PNG) kinase complex regulates the developmental translation of cyclin B. cyclin B mRNA becomes unmasked during oogenesis independent of PNG activity, but PNG is required for translation from egg activation. We find that although polyadenylation of cyclin B augments translation, it is not essential, and a fully elongated poly(A) is not required for translation to proceed. In fact, changes in poly(A) tail length are not sufficient to account for PNG-mediated control of cyclin B translation and of the early embryonic cell cycles. We present evidence that PNG functions instead as an antagonist of PUMILIO-dependent translational repression. Our data argue that changes in poly(A) tail length are not a universal mechanism governing embryonic cell cycles, and that PNG-mediated derepression of translation is an important alternative mechanism in Drosophila.
Russian translations for Cochrane.

Science.gov (United States)

Yudina, E V; Ziganshina, L E

2015-01-01

Cochrane collaboration has made a huge contribution to the development of evidence-based medicine; Cochrane work is the international gold standard of independent, credible and reliable high-quality information in medicine. Over the past 20 years the Cochrane Collaboration helped transforming decision-making in health and reforming it significantly, saving lives and contributing to longevity [1]. Until recently, Cochrane evidence were available only in English, which represents a significant barrier to their wider use in non-English speaking countries. To provide access to evidence, obtained from Cochrane Reviews, for health professionals and general public (from non-English-speaking countries), bypassing language barriers, Cochrane collaboration in 2014 initiated an international project of translating Plain language summaries of Cochrane Reviews into other languages [2, 3]. Russian translations of Plain language summaries were started in May 2014 by the team from Kazan Federal University (Department of Basic and Clinical Pharmacology; 2014-2015 as an Affiliated Centre in Tatarstan of the Nordic Cochrane Centre, since August 2015 as Cochrane Russia, a Russian branch of Cochrane Nordic, Head - Liliya Eugenevna Ziganshina) on a voluntary basis. To assess the quality of Russian translations of Cochrane Plain Language Summaries (PLS) and their potential impact on the Russian speaking community through user feedback with the overarching aim of furthering the translations project. We conducted the continuous online survey via Google Docs. We invited respondents through the electronic Russian language discussion forum on Essential Medicines (E-lek), links to survey on the Russian Cochrane.org website, invitations to Cochrane contributors registered in Archie from potential Russian-speaking countries. We set up the survey in Russian and English. The respondents were asked to respond to the questionnaire regarding the relevance and potential impact of the Cochrane Russian
A thermoelectric cap for seafloor hydrothermal vents

International Nuclear Information System (INIS)

Xie, Yu; Wu, Shi-jun; Yang, Can-jun

2016-01-01

Highlights: • We developed a thermoelectric cap (TC) to harvest hydrothermal energy. • The TC was deployed at a hydrothermal vent site near Kueishantao islet, Taiwan. • The TC monitored the temperature of the hydrothermal fluids during the field test. • The TC could make the thermal energy of hydrothermal fluids a viable power source. - Abstract: Long-term in situ monitoring is crucial to seafloor scientific investigations. One of the challenges of operating sensors in seabed is the lifespan of the sensors. Such sensors are commonly powered by batteries when other alternatives, such as tidal or solar energy, are unavailable. However, the batteries have a limited lifespan and must be recharged or replaced periodically, which is costly and impractical. A thermoelectric cap, which harvests the thermal energy of hydrothermal fluids through a conduction pipe and converts the heat to electrical energy by using thermoelectric generators, was developed to avoid these inconveniences. The thermoelectric cap was combined with a power and temperature measurement system that enables the thermoelectric cap to power a light-emitting diode lamp, an electronic load (60 Ω), and 16 thermocouples continuously. The thermoelectric cap was field tested at a shallow hydrothermal vent site near Kueishantao islet, which is located offshore of northeastern Taiwan. By using the thermal gradient between hydrothermal fluids and seawater, the thermoelectric cap obtained a sustained power of 0.2–0.5 W during the field test. The thermoelectric cap successfully powered the 16 thermocouples and recorded the temperature of the hydrothermal fluids during the entire field test. Our results show that the thermal energy of hydrothermal fluids can be an alternative renewable power source for oceanographic research.
Density functional study of condensation in capped capillaries.

Science.gov (United States)

Yatsyshin, P; Savva, N; Kalliadasis, S

2015-07-15

We study liquid adsorption in narrow rectangular capped capillaries formed by capping two parallel planar walls (a slit pore) with a third wall orthogonal to the two planar walls. The most important transition in confined fluids is arguably condensation, where the pore becomes filled with the liquid phase which is metastable in the bulk. Depending on the temperature T, the condensation in capped capillaries can be first-order (at T≤Tcw) or continuous (at T>Tcw), where Tcw is the capillary wetting temperature. At T>Tcw, the capping wall can adsorb mesoscopic amounts of metastable under-condensed liquid. The onset of condensation is then manifested by the continuous unbinding of the interface between the liquid adsorbed on the capping wall and the gas filling the rest of the capillary volume. In wide capped capillaries there may be a remnant of wedge filling transition, which is manifested by the adsorption of liquid drops in the corners. Our classical statistical mechanical treatment predicts a possibility of three-phase coexistence between gas, corner drops and liquid slabs adsorbed on the capping wall. In sufficiently wide capillaries we find that thick prewetting films of finite length may be nucleated at the capping wall below the boundary of the prewetting transition. Prewetting then proceeds in a continuous manner manifested by the unbinding interface between the thick and thin films adsorbed on the side walls. Our analysis is based on a detailed numerical investigation of the density functional theory for the fluid equilibria for a number of illustrative case studies.
Durability of Capped Wood Plastic Composites

Science.gov (United States)

Mark Mankowski; Mark J. Manning; Damien P. Slowik

2015-01-01

Manufacturers of wood plastic composites (WPCs) have recently introduced capped decking to their product lines. These new materials have begun to take market share from the previous generation of uncapped products that possessed a homogenous composition throughout the thickness of their cross-section. These capped offerings have been introduced with claims that the...
Translation in cell-free systems

International Nuclear Information System (INIS)

Jagus, R.

1987-01-01

The simplest, unambiguous identification of a particular mRNA is the identification of its protein product. This can be established by translation of the mRNA of interest in a cell-free protein-synthesizing system. Messenger RNA protein product identification is important in the isolation of a particular mRNA species for cDNA cloning and in the identification of positive cDNA clones. The two high-activity translation systems in common use are those prepared from rabbit reticulocytes and from wheat germ. Both systems are easy to prepare, and both are available commercially. Each has advantages and disadvantages over the other and a choice between the two will depend on the type of mRNAs to be translated, the prejudices of experience, and availability. The main disadvantage of the reticulocyte system is that it requires removal of endogenous mRNA. However, this is a relatively simple procedure. The wheat germ system does not require removal of endogenous mRNA and may translate weakly initiating mRNAs more efficiently. However, ionic optima for translation in the wheat germ system are more sensitive to the nature and concentration of mRNA and may need to be determined for each template. The biggest problem with the use of the wheat germ system is its tendency to produce incomplete translation products due to premature termination

ImmunoCAP assays: Pros and cons in allergology.

Science.gov (United States)

van Hage, Marianne; Hamsten, Carl; Valenta, Rudolf

2017-10-01

Allergen-specific IgE measurements and the clinical history are the cornerstones of allergy diagnosis. During the past decades, both characterization and standardization of allergen extracts and assay technology have improved. Here we discuss the uses, advantages, misinterpretations, and limitations of ImmunoCAP IgE assays (Thermo Fisher Scientific/Phadia, Uppsala, Sweden) in the field of allergology. They can be performed as singleplex (ImmunoCAP) and, for the last decade, as multiplex (Immuno Solid-phase Allergen Chip [ISAC]). The major benefit of ImmunoCAP is the obtained quantified allergen-specific IgE antibody level and the lack of interference from allergen-specific IgG antibodies. However, ImmunoCAP allergen extracts are limited to the composition of the extract. The introduction of allergen molecules has had a major effect on analytic specificity and allergy diagnosis. They are used in both singleplex ImmunoCAP and multiplex ImmunoCAP ISAC assays. The major advantage of ISAC is the comprehensive IgE pattern obtained with a minute amount of serum. The shortcomings are its semiquantitative measurements, lower linear range, and cost per assay. With respect to assay performance, ImmunoCAP allergen extracts are good screening tools, but allergen molecules dissect the IgE response on a molecular level and put allergy research on the map of precision medicine. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
AtLa1 protein initiates IRES-dependent translation of WUSCHEL mRNA and regulates the stem cell homeostasis of Arabidopsis in response to environmental hazards.

Science.gov (United States)

Cui, Yuchao; Rao, Shaofei; Chang, Beibei; Wang, Xiaoshuang; Zhang, Kaidian; Hou, Xueliang; Zhu, Xueyi; Wu, Haijun; Tian, Zhaoxia; Zhao, Zhong; Yang, Chengwei; Huang, Tao

2015-10-01

Plant stem cells are hypersensitive to environmental hazards throughout their life cycle, but the mechanism by which plants safeguard stem cell homeostasis in response to environmental hazards is largely unknown. The homeodomain transcription factor WUSCHEL (WUS) protein maintains the stem cell pool in the shoot apical meristem of Arabidopsis. Here, we demonstrate that the translation of WUS mRNA is directed by an internal ribosomal entry site (IRES) located in the 5'-untranslated region. The AtLa1 protein, an RNA-binding factor, binds to the 5'-untranslated region and initiates the IRES-dependent translation of WUS mRNA. Knockdown of AtLa1 expression represses the WUS IRES-dependent translation and leads to the arrest of growth and development. The AtLa1 protein is mainly located in the nucleoplasm. However, environmental hazards promote the nuclear-to-cytoplasmic translocation of the AtLa1 protein, which further enhances the IRES-dependent translation of WUS mRNA. Genetic evidence indicates that the WUS protein increases the tolerance of the shoot apical meristem to environmental hazards. Based on these results, we conclude that the stem cell niche in Arabidopsis copes with environmental hazards by enhancing the IRES-dependent translation of WUS mRNA under the control of the AtLa1 protein. © 2015 John Wiley & Sons Ltd.
The translation factors of Drosophila melanogaster.

Science.gov (United States)

Marygold, Steven J; Attrill, Helen; Lasko, Paul

2017-01-02

Synthesis of polypeptides from mRNA (translation) is a fundamental cellular process that is coordinated and catalyzed by a set of canonical 'translation factors'. Surprisingly, the translation factors of Drosophila melanogaster have not yet been systematically identified, leading to inconsistencies in their nomenclature and shortcomings in functional (Gene Ontology, GO) annotations. Here, we describe the complete set of translation factors in D. melanogaster, applying nomenclature already in widespread use in other species, and revising their functional annotation. The collection comprises 43 initiation factors, 12 elongation factors, 3 release factors and 6 recycling factors, totaling 64 of which 55 are cytoplasmic and 9 are mitochondrial. We also provide an overview of notable findings and particular insights derived from Drosophila about these factors. This catalog, together with the incorporation of the improved nomenclature and GO annotation into FlyBase, will greatly facilitate access to information about the functional roles of these important proteins.
The Influence of Company Size on Accounting Information: Evidence in Large Caps and Small Caps Companies Listed on BM&FBovespa

Directory of Open Access Journals (Sweden)

Karen Yukari Yokoyama

2015-09-01

Full Text Available In this study, the relation between accounting information aspects and the capitalization level o companies listed on the São Paulo Stock Exchange was investigated, classified as Large Caps or Small Caps, companies with larger and smaller capitalization, respectively, between 2010 and 2012. Three accounting information measures were addressed: informativeness, conservatism and relevance, through the application of Easton and Harris’ (1991 models of earnings informativeness, Basu’s (1997 model of conditional conservatism and the value relevance model, based on Ohlson (1995. The results appointed that, although the Large Caps present a higher level of conservatism, their accounting figures were less informative and more relevant when compared to the Large Caps companies. Due to the greater production of private information (predisclosure surrounding larger companies, the market would tend to respond less strongly or surprised to the publication of these companies’ accounting information, while the lack of anticipated information would make the effect of disclosing these figures more preponderant for the Small Caps companies.
Red Blood Cell Transfusion Independence Following the Initiation of Iron Chelation Therapy in Myelodysplastic Syndrome

Directory of Open Access Journals (Sweden)

Maha A. Badawi

2010-01-01

Full Text Available Iron chelation therapy is often used to treat iron overload in patients requiring transfusion of red blood cells (RBC. A 76-year-old man with MDS type refractory cytopenia with multilineage dysplasia, intermediate-1 IPSS risk, was referred when he became transfusion dependent. He declined infusional chelation but subsequently accepted oral therapy. Following the initiation of chelation, RBC transfusion requirement ceased and he remained transfusion independent over 40 months later. Over the same time course, ferritin levels decreased but did not normalize. There have been eighteen other MDS patients reported showing improvement in hemoglobin level with iron chelation; nine became transfusion independent, nine had decreased transfusion requirements, and some showed improved trilineage myelopoiesis. The clinical features of these patients are summarized and possible mechanisms for such an effect of iron chelation on cytopenias are discussed.
Recessive Resistance to Plant Viruses: Potential Resistance Genes Beyond Translation Initiation Factors

Directory of Open Access Journals (Sweden)

Masayoshi Hashimoto

2016-10-01

Full Text Available The ability of plant viruses to propagate their genomes in host cells depends on many host factors. In the absence of an agrochemical that specifically targets plant viral infection cycles, one of the most effective methods for controlling viral diseases in plants is taking advantage of the host plant’s resistance machinery. Recessive resistance is conferred by a recessive gene mutation that encodes a host factor critical for viral infection. It is a branch of the resistance machinery and, as an inherited characteristic, is very durable. Moreover, recessive resistance may be acquired by a deficiency in a negative regulator of plant defense responses, possibly due to the autoactivation of defense signaling. Eukaryotic translation initiation factor (eIF 4E and eIF4G and their isoforms are the most widely exploited recessive resistance genes in several crop species, and they are effective against a subset of viral species. However, the establishment of efficient, recessive resistance-type antiviral control strategies against a wider range of plant viral diseases requires genetic resources other than eIF4Es. In this review, we focus on recent advances related to antiviral recessive resistance genes evaluated in model plants and several crop species. We also address the roles of next-generation sequencing and genome editing technologies in improving plant genetic resources for recessive resistance-based antiviral breeding in various crop species.
Contabilidad de Costos II. - Capítulo 4. Respuestas

OpenAIRE

Morillo Moreno, Marysela C.

2008-01-01

ÍNDICE Presentación Orientaciones para el usuario Capítulo 1: Contabilidad de costos por procesos Sistemas de Contabilidad de Costos por Proceso Costos de Producción Conjunta. Productos Principales y Secundarios Capítulo 2: Contabilidad de costos predeterminados Presupuesto Estático y Presupuesto Flexible Sistema de Costos Estándar Capítulo 3: Sistema de costos variables Capítulo 4: Respuestas Bibliografía recomendada Pr...
Regulation of mRNA translation influences hypoxia tolerance

International Nuclear Information System (INIS)

Koritzinsky, M.; Wouters, B.G.; Koumenis, C.

2003-01-01

Hypoxia is a heterogenous but common characteristic of human tumours and poor oxygenation is associated with poor prognosis. We believe that the presence of viable hypoxic tumor cells reflects in part an adaptation and tolerance of these cells to oxygen deficiency. Since oxidative phosphorylation is compromized during hypoxia, adaptation may involve both the upregulation of glycolysis as well as downregulation of energy consumption. mRNA translation is one of the most energy costly cellular processes, and we and others have shown that global mRNA translation is rapidly inhibited during hypoxia. However, some mRNAs, including those coding for HIF-1 α and VEGF, remain efficiently translated during hypoxia. Clearly, the mechanisms responsible for the overall inhibition of translation during hypoxia does not compromize the translation of certain hypoxia-induced mRNA species. We therefore hypothesize that the inhibition of mRNA translation serves to promote hypoxia tolerance in two ways: i) through conservation of energy and ii) through differential gene expression involved in hypoxia adaptation. We have recently identified two pathways that are responsible for the global inhibition of translation during hypoxia. The phosphorylation of the eukaryotic initiation factor eIF2 α by the ER resident kinase PERK results in down-regulation of protein synthesis shortly after the onset of hypoxia. In addition, the initiation complex eIF4F is disrupted during long lasting hypoxic conditions. The identification of the molecular pathways responsible for the inhibition of overall translation during hypoxia has rendered it possible to investigate their importance for hypoxia tolerance. We have found that mouse embryo fibroblasts that are knockout for PERK and therefore not able to inhibit protein synthesis efficiently during oxygen deficiency are significantly less tolerant to hypoxia than their wildtype counterparts. We are currently also investigating the functional significance
22 CFR 121.11 - Military demolition blocks and blasting caps.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Military demolition blocks and blasting caps... blasting caps. Military demolition blocks and blasting caps referred to in Category IV(a) do not include the following articles: (a) Electric squibs. (b) No. 6 and No. 8 blasting caps, including electric...
A Fourier-series-based kernel-independent fast multipole method

International Nuclear Information System (INIS)

Zhang Bo; Huang Jingfang; Pitsianis, Nikos P.; Sun Xiaobai

2011-01-01

We present in this paper a new kernel-independent fast multipole method (FMM), named as FKI-FMM, for pairwise particle interactions with translation-invariant kernel functions. FKI-FMM creates, using numerical techniques, sufficiently accurate and compressive representations of a given kernel function over multi-scale interaction regions in the form of a truncated Fourier series. It provides also economic operators for the multipole-to-multipole, multipole-to-local, and local-to-local translations that are typical and essential in the FMM algorithms. The multipole-to-local translation operator, in particular, is readily diagonal and does not dominate in arithmetic operations. FKI-FMM provides an alternative and competitive option, among other kernel-independent FMM algorithms, for an efficient application of the FMM, especially for applications where the kernel function consists of multi-physics and multi-scale components as those arising in recent studies of biological systems. We present the complexity analysis and demonstrate with experimental results the FKI-FMM performance in accuracy and efficiency.
Mapping Translation Technology Research in Translation Studies

DEFF Research Database (Denmark)

Schjoldager, Anne; Christensen, Tina Paulsen; Flanagan, Marian

2017-01-01

section aims to improve this situation by presenting new and innovative research papers that reflect on recent technological advances and their impact on the translation profession and translators from a diversity of perspectives and using a variety of methods. In Section 2, we present translation......Due to the growing uptake of translation technology in the language industry and its documented impact on the translation profession, translation students and scholars need in-depth and empirically founded knowledge of the nature and influences of translation technology (e.g. Christensen....../Schjoldager 2010, 2011; Christensen 2011). Unfortunately, the increasing professional use of translation technology has not been mirrored within translation studies (TS) by a similar increase in research projects on translation technology (Munday 2009: 15; O’Hagan 2013; Doherty 2016: 952). The current thematic...
The association between continuous antibiotic prophylaxis and UTI from birth until initial postnatal imaging evaluation among newborns with antenatal hydronephrosis.

Science.gov (United States)

Varda, B K; Finkelstein, J B; Wang, H-H; Logvinenko, T; Nelson, C P

2018-05-29

There is a lack of consensus regarding the use of continuous antibiotic prophylaxis (CAP) during the interval between birth and initial postnatal imaging in infants with a history of antenatal urinary tract dilation (AUTD). To determine the incidence of urinary tract infection (UTI), and the association between CAP use and UTI during the interval between birth and the first postnatal renal ultrasound (RUS) in infants with AUTD. A single-institution, retrospective cohort study of newborns with a history of AUTD. Infants undergoing RUS within 3 months of birth for an indication of 'hydronephrosis' between 2012 and 2014 were identified. A random sample of 500 infants was selected; six were excluded for concomitant congenital anomalies. Baseline patient (sex, race, insurance) and clinical characteristics (circumcision status, UTD risk score, receipt of CAP, UTI prior to RUS, age at UTI, and age at RUS) were collected via retrospective chart review. Descriptive statistics were calculated. To adjust for receipt of CAP, propensity score adjusted univariate logistic regression for UTI based on CAP status was performed. Among the 494 infants with AUTD, 157 (32%) received CAP. Infants with normal/low-risk UTD scores were less likely to receive CAP than those with medium/high-risk UTD (23% vs 77%; P UTI prior to imaging: six (1.8%) without CAP vs one (0.64%) with CAP (P = 0.44). The median age at UTI was 59 days (range 2-84); among those with UTI, initial imaging occurred significantly later (66 vs 28 days; P = 0.001). The propensity score adjusted odds of developing UTI with CAP (vs without) was 0.93 (95% CI 0.10-8.32; P = 0.95). The Summary Figure describes the infants with UTI. The incidence of UTI prior to initial neonatal imaging in newborns with AUTD was low. Use of CAP was not associated with UTI incidence after adjusting for UTD severity. Routine use of CAP in newborns with AUTD prior to initial imaging may be of limited benefit in most patients. Copyright �
Amplified in Breast Cancer Regulates Transcription and Translation in Breast Cancer Cells.

Science.gov (United States)

Ochnik, Aleksandra M; Peterson, Mark S; Avdulov, Svetlana V; Oh, Annabell S; Bitterman, Peter B; Yee, Douglas

2016-02-01

Control of mRNA translation is fundamentally altered in cancer. Insulin-like growth factor-I (IGF-I) signaling regulates key translation mediators to modulate protein synthesis (e.g. eIF4E, 4E-BP1, mTOR, and S6K1). Importantly the Amplified in Breast Cancer (AIB1) oncogene regulates transcription and is also a downstream mediator of IGF-I signaling. To determine if AIB1 also affects mRNA translation, we conducted gain and loss of AIB1 function experiments in estrogen receptor alpha (ERα)(+) (MCF-7L) and ERα(-) (MDA-MB-231, MDA-MB-435 and LCC6) breast cancer cells. AIB1 positively regulated IGF-I-induced mRNA translation in both ERα(+) and ERα(-) cells. Formation of the eIF4E-4E-BP1 translational complex was altered in the AIB1 ERα(+) and ERα(-) knockdown cells, leading to a reduction in the eIF4E/4E-BP1 and eIF4G/4E-BP1 ratios. In basal and IGF-I stimulated MCF-7 and LCC6 cells, knockdown of AIB1 decreased the integrity of the cap-binding complex, reduced global IGF-I stimulated polyribosomal mRNA recruitment with a concomitant decrease in ten of the thirteen genes tested in polysome-bound mRNAs mapping to proliferation, cell cycle, survival, transcription, translation and ribosome biogenesis ontologies. Specifically, knockdown of AIB1 decreased ribosome-bound mRNA and steady-state protein levels of the transcription factors ERα and E2F1 in addition to reduced ribosome-bound mRNA of the ribosome biogenesis factor BYSL in a cell-line specific manner to regulate mRNA translation. The oncogenic transcription factor AIB1 has a novel role in the regulation of polyribosome recruitment and formation of the translational complex. Combinatorial therapies targeting IGF signaling and mRNA translation in AIB1 expressing breast cancers may have clinical benefit and warrants further investigation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Critical parameters influencing the EUV-induced damage of Ru-capped multilayer mirrors

International Nuclear Information System (INIS)

Hill, S B; Ermanoski, I; Tarrio, C; Lucatorto, T B; Madey, T E; Bajt, S; Fang, M; Chandhok, M

2007-01-01

Ongoing endurance testing of Ru-capped multilayer mirrors (MLMs) at the NIST synchrotron facility has revealed that the damage resulting from EUV irradiation does not always depend on the exposure conditions in an intuitive way. Previous exposures of Ru-capped MLMs to EUV radiation in the presence of water vapor demonstrated that the mirror damage rate actually decreases with increasing water pressure. We will present results of recent exposures showing that the reduction in damage for partial pressures of water up to 5 x 10 -6 Torr is not the result of a spatially uniform decrease in damage across the Gaussian intensity distribution of the incident EUV beam. Instead we observe a drop in the damage rate in the center of the exposure spot where the intensity is greatest, while the reflectivity loss in the wings of the intensity distribution appears to be independent of water partial pressure. (See Fig. 1.) We will discuss how the overall damage rate and spatial profile can be influenced by admixtures of carbon-containing species (e.g., CO, CO 2 , C 6 H 6 ) at partial pressures one-to-two orders of magnitude lower than the water vapor partial pressure. An investigation is underway to find the cause of the non-Gaussian damage profile. Preliminary results and hypotheses will be discussed. In addition to high-resolution reflectometry of the EUV-exposure sites, the results of surface analysis such as XPS will be presented. We will also discuss how the bandwidth and time structure of incident EUV radiation may affect the rate of reflectivity degradation. Although the observations presented here are based on exposures of Ru-capped MLMs, unless novel capping layers are similarly characterized, direct application of accelerated testing results could significantly overestimate mirror lifetime in the production environment
Electrochemical deposition mechanism of calcium phosphate coating in dilute Ca-P electrolyte system

Energy Technology Data Exchange (ETDEWEB)

Hu Ren [State Key Laboratory of Physical Chemistry of Solid Surfaces and Department of Chemistry, CNRS Laboratoire International Associe XiamENS, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005 (China); Department of Biology, College of Life Science, Xiamen University, Xiamen, Fujian 361005 (China); Lin Changjian, E-mail: cjlin@xmu.edu.cn [State Key Laboratory of Physical Chemistry of Solid Surfaces and Department of Chemistry, CNRS Laboratoire International Associe XiamENS, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005 (China); Shi Haiyan; Wang Hui [State Key Laboratory of Physical Chemistry of Solid Surfaces and Department of Chemistry, CNRS Laboratoire International Associe XiamENS, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005 (China)

2009-06-15

In this work, the electrochemical deposition behavior of calcium phosphate coating from an aqueous electrolyte containing very dilute calcium and phosphorus species (Ca-P) was studied. The effects of three process parameters, i.e. temperature, current density and duration, were systematically investigated and the underlying mechanism was thoroughly analyzed. It was observed that the coating is mainly composed of hydroxyapatite (HA) in a wide range of temperature and current densities. The temperature had a significant effect on the deposition velocity. An apparent activation energy of 174.9 kJ mol{sup -1} was subsequently derived, indicating the mass-transfer control mechanism for the coating formation. The current density was identified to be an important parameter for structure controllability. The results of DR-FTIR/Raman spectroscopic studies of the initial deposition phase strongly suggested that the HA coating was instantaneously and directly precipitated on the substrate; neither induction period nor precursor was detected in this dilute Ca-P electrolyte system. Finally, a phase diagram of the Ca-P electrolyte system was constructed, which offered a thermodynamic reason for the direct single-phase HA precipitation observed only in this system, but not in conventional concentrated systems.
Electrochemical deposition mechanism of calcium phosphate coating in dilute Ca-P electrolyte system

International Nuclear Information System (INIS)

Hu Ren; Lin Changjian; Shi Haiyan; Wang Hui

2009-01-01

In this work, the electrochemical deposition behavior of calcium phosphate coating from an aqueous electrolyte containing very dilute calcium and phosphorus species (Ca-P) was studied. The effects of three process parameters, i.e. temperature, current density and duration, were systematically investigated and the underlying mechanism was thoroughly analyzed. It was observed that the coating is mainly composed of hydroxyapatite (HA) in a wide range of temperature and current densities. The temperature had a significant effect on the deposition velocity. An apparent activation energy of 174.9 kJ mol -1 was subsequently derived, indicating the mass-transfer control mechanism for the coating formation. The current density was identified to be an important parameter for structure controllability. The results of DR-FTIR/Raman spectroscopic studies of the initial deposition phase strongly suggested that the HA coating was instantaneously and directly precipitated on the substrate; neither induction period nor precursor was detected in this dilute Ca-P electrolyte system. Finally, a phase diagram of the Ca-P electrolyte system was constructed, which offered a thermodynamic reason for the direct single-phase HA precipitation observed only in this system, but not in conventional concentrated systems.
Prices regulation in price-cap: the lessons of the british gas industry; Reglementations tarifaires en price-cap: les lecons de l'industrie gaziere anglaise

Energy Technology Data Exchange (ETDEWEB)

David, L.

2003-07-01

This article examines the problem of the price-cap regulation applied to the british gas transport. The RPI-X cap is a particular form of the price cap. This cap seems to be more remunerative for the regulatory firm than a cap calculated on the Laspeyres index because it authorizes a greater freedom of prices choice, to the prejudice of the consumers. Facing these perverse effects, Cowan proposed in 1997 a new system, not more satisfying. Another equation is analyzed in this article, proposed by Ofgem. Meanwhile this system presents no improvement of the consumers surplus facing the RPI-X cap. (A.L.B.)
Translation of SNOMED CT - strategies and description of a pilot project.

Science.gov (United States)

Klein, Gunnar O; Chen, Rong

2009-01-01

The translation and localization of SNOMED CT (Systematized Nomenclature of Medicine - Clinical Terms) have been initiated in a few countries. In Sweden, we conducted the first evaluation of this terminology in a project called REFTERM in which we also developed a software tool which could handle a large scale translation with a number of translators and reviewers in a web-based environment. The system makes use of existing authorized English-Swedish translations of medical terminologies such as ICD-10. The paper discusses possible strategies for a national project to translate and adapt this terminology.
IN SITU REMEDIATION OF CONTAMINATED SEDIMENTS - ACTIVE CAPPING TECHNOLOGY

Energy Technology Data Exchange (ETDEWEB)

Knox, A.; Roberts, J.; Paller, M.; Reible, D.

2010-09-02

Active capping is a relatively new approach for treating contaminated sediments. It involves applying chemically reactive amendments to the sediment surface. The main role of active caps is to stabilize contaminants in contaminated sediments, lower the bioavailable pool of contaminants, and reduce the release of contaminants to the water column. Metals are common contaminants in many marine and fresh water environments as a result of industrial and military activities. The mobile, soluble forms of metals are generally considered toxic. Induced chemical precipitation of these metals can shift toxic metals from the aqueous phase to a solid, precipitated phase which is often less bioavailable. This approach can be achieved through application of sequestering agents such as rock phosphates, organoclays, zeolites, clay minerals, and biopolymers (e.g., chitosan) in active capping technology. Active capping holds great potential for a more permanent solution that avoids residual risks resulting from contaminant migration through the cap or breaching of the cap. In addition to identifying superior active capping agents, research is needed to optimize application techniques, application rates, and amendment combinations that maximize sequestration of contaminants. A selected set of active capping treatment technologies has been demonstrated at a few sites, including a field demonstration at the Savannah River Site, Aiken, SC. This demonstration has provided useful information on the effects of sequestering agents on metal immobilization, bioavailability, toxicity, and resistance to mechanical disturbance.
In Situ Remediation Of Contaminated Sediments - Active Capping Technology

International Nuclear Information System (INIS)

Knox, A.; Roberts, J.; Paller, M.; Reible, D.

2010-01-01

Active capping is a relatively new approach for treating contaminated sediments. It involves applying chemically reactive amendments to the sediment surface. The main role of active caps is to stabilize contaminants in contaminated sediments, lower the bioavailable pool of contaminants, and reduce the release of contaminants to the water column. Metals are common contaminants in many marine and fresh water environments as a result of industrial and military activities. The mobile, soluble forms of metals are generally considered toxic. Induced chemical precipitation of these metals can shift toxic metals from the aqueous phase to a solid, precipitated phase which is often less bioavailable. This approach can be achieved through application of sequestering agents such as rock phosphates, organoclays, zeolites, clay minerals, and biopolymers (e.g., chitosan) in active capping technology. Active capping holds great potential for a more permanent solution that avoids residual risks resulting from contaminant migration through the cap or breaching of the cap. In addition to identifying superior active capping agents, research is needed to optimize application techniques, application rates, and amendment combinations that maximize sequestration of contaminants. A selected set of active capping treatment technologies has been demonstrated at a few sites, including a field demonstration at the Savannah River Site, Aiken, SC. This demonstration has provided useful information on the effects of sequestering agents on metal immobilization, bioavailability, toxicity, and resistance to mechanical disturbance.

Trans-acting translational regulatory RNA binding proteins.

Science.gov (United States)

Harvey, Robert F; Smith, Tom S; Mulroney, Thomas; Queiroz, Rayner M L; Pizzinga, Mariavittoria; Dezi, Veronica; Villenueva, Eneko; Ramakrishna, Manasa; Lilley, Kathryn S; Willis, Anne E

2018-05-01

The canonical molecular machinery required for global mRNA translation and its control has been well defined, with distinct sets of proteins involved in the processes of translation initiation, elongation and termination. Additionally, noncanonical, trans-acting regulatory RNA-binding proteins (RBPs) are necessary to provide mRNA-specific translation, and these interact with 5' and 3' untranslated regions and coding regions of mRNA to regulate ribosome recruitment and transit. Recently it has also been demonstrated that trans-acting ribosomal proteins direct the translation of specific mRNAs. Importantly, it has been shown that subsets of RBPs often work in concert, forming distinct regulatory complexes upon different cellular perturbation, creating an RBP combinatorial code, which through the translation of specific subsets of mRNAs, dictate cell fate. With the development of new methodologies, a plethora of novel RNA binding proteins have recently been identified, although the function of many of these proteins within mRNA translation is unknown. In this review we will discuss these methodologies and their shortcomings when applied to the study of translation, which need to be addressed to enable a better understanding of trans-acting translational regulatory proteins. Moreover, we discuss the protein domains that are responsible for RNA binding as well as the RNA motifs to which they bind, and the role of trans-acting ribosomal proteins in directing the translation of specific mRNAs. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes Translation > Translation Regulation Translation > Translation Mechanisms. © 2018 Medical Research Council and University of Cambridge. WIREs RNA published by Wiley Periodicals, Inc.
Cause for concern? Attitudes towards translation crowdsourcing in professional translators’ blogs

DEFF Research Database (Denmark)

Flanagan, Marian

2016-01-01

This paper seeks to identify professional translators’ attitudes towards the practice of translation crowdsourcing. The data consist of 48 professional translator blogs. A thematic analysis of their blog posts highlights three main findings: translation crowdsourcing can enhance visibility...... do not openly discuss their motives for differentiating between the various non-profit initiatives, and while there is much discussion on translation crowdsourcing for humanitarian causes, little or no attention is paid to free and open source software projects....
VERSIONS VERSUS BODIES: TRANSLATIONS IN THE MISSIONARY ENCOUNTER IN AMAZONIA

OpenAIRE

Vilaça, Aparecida

2016-01-01

Abstract This paper analyzes the two distinct concepts of translation at work in the encounter between the Amazonian Wari' and the New Tribes Mission evangelical missionaries, and the equivocations stemming from this difference. While the missionaries conceive translation as a process of converting meanings between languages, conceived as linguistic codes that exist independently of culture, for the Wari', in consonance with their perspectivist ontology, it is not language that differentiates...
Suppressed translation as a mechanism of initiation of CASP8 (caspase 8)-dependent apoptosis in autophagy-deficient NSCLC cells under nutrient limitation.

Science.gov (United States)

Allavena, Giulia; Cuomo, Francesca; Baumgartner, Georg; Bele, Tadeja; Sellgren, Alexander Yarar; Oo, Kyaw Soe; Johnson, Kaylee; Gogvadze, Vladimir; Zhivotovsky, Boris; Kaminskyy, Vitaliy O

2018-01-01

Macroautophagy/autophagy inhibition under stress conditions is often associated with increased cell death. We found that under nutrient limitation, activation of CASP8/caspase-8 was significantly increased in autophagy-deficient lung cancer cells, which precedes mitochondria outer membrane permeabilization (MOMP), CYCS/cytochrome c release, and activation of CASP9/caspase-9, indicating that under such conditions the activation of CASP8 is a primary event in the initiation of apoptosis as well as essential to reduce clonogenic survival of autophagy-deficient cells. Starvation leads to suppression of CFLAR proteosynthesis and accumulation of CASP8 in SQSTM1 puncta. Overexpression of CFLARs reduces CASP8 activation and apoptosis during starvation, while its silencing promotes efficient activation of CASP8 and apoptosis in autophagy-deficient U1810 lung cancer cells even under nutrient-rich conditions. Similar to starvation, inhibition of protein translation leads to efficient activation of CASP8 and cell death in autophagy-deficient lung cancer cells. Thus, here for the first time we report that suppressed translation leads to activation of CASP8-dependent apoptosis in autophagy-deficient NSCLC cells under conditions of nutrient limitation. Our data suggest that targeting translational machinery can be beneficial for elimination of autophagy-deficient cells via the CASP8-dependent apoptotic pathway.
Lowering the YE+1 end-cap for CMS

CERN Multimedia

Maximilien Brice

2007-01-01

On 9 January 2007, the massive YE+1 end-cap was lowered into the CMS cavern. This is a very precise process as the crane must lower the end-cap through minimal clearance without tilt or sway. Once in the cavern, the end-cap is then positioned over the end of the barrel to detect particles produced in collisions that travel close to the axis of the beams.
Mitochondrial Respiration Inhibitors Suppress Protein Translation and Hypoxic Signaling via the Hyperphosphorylation and Inactivation of Translation Initiation Factor eIF2α and Elongation Factor eEF2

Science.gov (United States)

Li, Jun; Mahdi, Fakhri; Du, Lin; Datta, Sandipan; Nagle, Dale G.; Zhou, Yu-Dong

2011-01-01

Over 20000 lipid extracts of plants and marine organisms were evaluated in a human breast tumor T47D cell-based reporter assay for hypoxia-inducible factor-1 (HIF-1) inhibitory activity. Bioassay-guided isolation and dereplication-based structure elucidation of an active extract from the Bael tree (Aegle marmelos) afforded two protolimonoids, skimmiarepin A (1) and skimmiarepin C (2). In T47D cells, 1 and 2 inhibited hypoxia-induced HIF-1 activation with IC50 values of 0.063 µM and 0.068 µM, respectively. Compounds 1 and 2 also suppressed hypoxic induction of the HIF-1 target genes GLUT-1 and VEGF. Mechanistic studies revealed that 1 and 2 inhibited HIF-1 activation by blocking the hypoxia-induced accumulation of HIF-1α protein. At the range of concentrations that inhibited HIF-1 activation, 1 and 2 suppressed cellular respiration by selectively inhibiting the mitochondrial electron transport chain at complex I (NADH dehydrogenase). Further investigation indicated that mitochondrial respiration inhibitors such as 1 and rotenone induced the rapid hyperphosphorylation and inhibition of translation initiation factor eIF2α and elongation factor eEF2. The inhibition of protein translation may account for the short-term exposure effects exerted by mitochondrial inhibitors on cellular signaling, while the suppression of cellular ATP production may contribute to the inhibitory effects following extended treatment periods. PMID:21875114
Microtubule dynamics: Caps, catastrophes, and coupled hydrolysis

DEFF Research Database (Denmark)

Flyvbjerg, H.; Holy, T.E.; Leibler, S.

1996-01-01

An effective theory is formulated for the dynamics of the guanosine triphosphate (GTP) cap believed to stabilize growing microtubules. The theory provides a ''coarse-grained'' description of the cap's dynamics. ''Microscopic'' details, such as the microtubule lattice structure and the fate of its...
Genome-Scale Analysis of Translation Elongation with a Ribosome Flow Model

Science.gov (United States)

Meilijson, Isaac; Kupiec, Martin; Ruppin, Eytan

2011-01-01

We describe the first large scale analysis of gene translation that is based on a model that takes into account the physical and dynamical nature of this process. The Ribosomal Flow Model (RFM) predicts fundamental features of the translation process, including translation rates, protein abundance levels, ribosomal densities and the relation between all these variables, better than alternative (‘non-physical’) approaches. In addition, we show that the RFM can be used for accurate inference of various other quantities including genes' initiation rates and translation costs. These quantities could not be inferred by previous predictors. We find that increasing the number of available ribosomes (or equivalently the initiation rate) increases the genomic translation rate and the mean ribosome density only up to a certain point, beyond which both saturate. Strikingly, assuming that the translation system is tuned to work at the pre-saturation point maximizes the predictive power of the model with respect to experimental data. This result suggests that in all organisms that were analyzed (from bacteria to Human), the global initiation rate is optimized to attain the pre-saturation point. The fact that similar results were not observed for heterologous genes indicates that this feature is under selection. Remarkably, the gap between the performance of the RFM and alternative predictors is strikingly large in the case of heterologous genes, testifying to the model's promising biotechnological value in predicting the abundance of heterologous proteins before expressing them in the desired host. PMID:21909250
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.
Who's (Still) Above the Social Security Payroll Tax Cap?

OpenAIRE

Nicole Woo; Janelle Jones; John Schmitt

2012-01-01

The Social Security payroll tax cap is the earnings level above which no further Social Security taxes are collected. The cap is currently at $110,100, though legislation has been introduced in Congress to apply the Social Security payroll tax to earnings above $250,000 (but not between the current cap and this level). This issue brief updates earlier work, finding that 5.8 percent of workers would be affected if the Social Security cap were eliminated entirely and 1.4 percent would be affect...
Translation and cultural adaptation of the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS v2.0).

Science.gov (United States)

Santos, Maria Fernanda Oliveira; Barros, Cristina Palmer; Silva, Carlos Henrique Martins da; Paro, Helena Borges Martins da Silva

2017-11-04

To translate and culturally adapt the Pediatric Eosinophilic Esophagitis Symptom Score (version 2.0), a tool used to assess pediatric eosinophilic esophagitis symptoms reported by patients and/or their parents/caregivers. The Pediatric Eosinophilic Esophagitis Symptom Score was translated through the following stages: initial translation, back-translation, and consensus of independent reviewers through the Delphi technique. The pre-final version of the Pediatric Eosinophilic Esophagitis Symptom Score was applied to five 8-to-18-year-old patients and to ten parents of two-to-18-year-old patients from an outpatient pediatric gastroenterology service (pre-test). During the translation process, no translations presenting with difficult consensus in the review process or grammar inconsistencies were observed. During the pre-test, difficulties in comprehension of some unconventional terms, e.g., "náusea", were observed. Adverbs of frequency, such as "quase nunca" were also identified as being of difficult understanding by patients and parents, and the substitution by the term "raramente" was suggested. Such difficulties may be inherent to the pediatric age group. Age 8 years or above should be considered adequate for the self-reporting of symptoms. The study presents the Brazilian version of the Pediatric Eosinophilic Esophagitis Symptom Score, which is adapted to the Brazilian culture. This version may be introduced as a clinical and research tool for the assessment of patients with esophagic disease symptoms. The Pediatric Eosinophilic Esophagitis Symptom Score is a breakthrough in the evaluation of symptoms of pediatric eosinophilic esophagitis, since it reinforces the importance of self-reporting by patients who experience this disease. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.
/sup 56/Fe (. gamma. ,. cap alpha. /sub 0/) reaction

Energy Technology Data Exchange (ETDEWEB)

Tamae, T; Sugawara, M [Tohoku Univ., Sendai (Japan). Lab. of Nuclear Science; Tsubota, H

1974-12-01

The reaction cross section of /sup 56/Fe (..gamma.., ..cap alpha../sub 0/) was measured from the electron energy of 15 to 25 MeV. The measured data were compared with the calculated ones based on statistic theory. Both agreed with each other. Therefore, the affirmative result was obtained for the presumption that the reaction of (..gamma.., ..cap alpha../sub 0/) of the nuclei around these energy levels can be explained by the statistical theory. The angular distribution of /sup 56/Fe (..gamma.., ..cap alpha../sub 0/) with 17 MeV electron energy was also measured, and the E2/E1 ratio was obtained. In the measurement of the /sup 56/Fe ( Gamma , ..cap alpha../sub 0/) reaction cross section, a natural target of 2.69 mg/cm/sup 2/ was irradiated with an electron beam with energy from 15 MeV to 25 MeV at intervals of 0.5 MeV, and the emitted ..cap alpha.. particles were detected by a broad band magnetic distribution meter. The measured cross section of the (..gamma.., ..cap alpha../sub 0/) reaction agreed with the calculated one based on statistical theory. If this fact is recognized in many nuclei, the cross section of the (..gamma.., ..cap alpha../sub 0/) reaction on those nuclei has the following characteristics. When the increasing rate of the product of a complex nucleus formation cross section and ..cap alpha../sub 0/ penetration factor is larger than that of the sum of all penetration factors of possible channels, the cross section of the (..gamma.., ..cap alpha../sub 0/) reaction increases, and takes a peak value when the above two increasing rates agree with each other.
Lack of anomalous diffusion in linear translationally-invariant systems determined by only one initial condition

International Nuclear Information System (INIS)

Khorrami, Mohammad; Shariati, Ahmad; Aghamohammadi, Amir; Fatollahi, Amir H.

2012-01-01

It is shown that as far as the linear diffusion equation meets both time- and space-translational invariance, the time dependence of a moment of degree α is a polynomial of degree at most equal to α, while all connected moments are at most linear functions of time. As a special case, the variance is an at most linear function of time. -- Highlights: ► The sufficient conditions for having the non-anomalous diffusion are given. ► Conditions are linearity, space-time translation invariance, solution uniqueness. ► Some versions of the fractional derivatives lack the translational invariance. ► It is shown the encoded inhomogeneity in derivatives causes anomalous behavior.
Lack of anomalous diffusion in linear translationally-invariant systems determined by only one initial condition

Energy Technology Data Exchange (ETDEWEB)

Khorrami, Mohammad, E-mail: mamwad@mailaps.org [Department of Physics, Alzahra University, Tehran 19938-93973 (Iran, Islamic Republic of); Shariati, Ahmad, E-mail: shariati@mailaps.org [Department of Physics, Alzahra University, Tehran 19938-93973 (Iran, Islamic Republic of); Aghamohammadi, Amir, E-mail: mohamadi@alzahra.ac.ir [Department of Physics, Alzahra University, Tehran 19938-93973 (Iran, Islamic Republic of); Fatollahi, Amir H., E-mail: ahfatol@gmail.com [Department of Physics, Alzahra University, Tehran 19938-93973 (Iran, Islamic Republic of)

2012-01-16

It is shown that as far as the linear diffusion equation meets both time- and space-translational invariance, the time dependence of a moment of degree α is a polynomial of degree at most equal to α, while all connected moments are at most linear functions of time. As a special case, the variance is an at most linear function of time. -- Highlights: ► The sufficient conditions for having the non-anomalous diffusion are given. ► Conditions are linearity, space-time translation invariance, solution uniqueness. ► Some versions of the fractional derivatives lack the translational invariance. ► It is shown the encoded inhomogeneity in derivatives causes anomalous behavior.
A decision tool for selecting trench cap designs

Energy Technology Data Exchange (ETDEWEB)

Paige, G.B.; Stone, J.J.; Lane, L.J. [USDA-ARS, Tucson, AZ (United States)] [and others

1995-12-31

A computer based prototype decision support system (PDSS) is being developed to assist the risk manager in selecting an appropriate trench cap design for waste disposal sites. The selection of the {open_quote}best{close_quote} design among feasible alternatives requires consideration of multiple and often conflicting objectives. The methodology used in the selection process consists of: selecting and parameterizing decision variables using data, simulation models, or expert opinion; selecting feasible trench cap design alternatives; ordering the decision variables and ranking the design alternatives. The decision model is based on multi-objective decision theory and uses a unique approach to order the decision variables and rank the design alternatives. Trench cap designs are evaluated based on federal regulations, hydrologic performance, cover stability and cost. Four trench cap designs, which were monitored for a four year period at Hill Air Force Base in Utah, are used to demonstrate the application of the PDSS and evaluate the results of the decision model. The results of the PDSS, using both data and simulations, illustrate the relative advantages of each of the cap designs and which cap is the {open_quotes}best{close_quotes} alternative for a given set of criteria and a particular importance order of those decision criteria.
Immunoprecipitation of Tri-methylated Capped RNA.

Science.gov (United States)

Hayes, Karen E; Barr, Jamie A; Xie, Mingyi; Steitz, Joan A; Martinez, Ivan

2018-02-05

Cellular quiescence (also known as G 0 arrest) is characterized by reduced DNA replication, increased autophagy, and increased expression of cyclin-dependent kinase p27 Kip1 . Quiescence is essential for wound healing, organ regeneration, and preventing neoplasia. Previous findings indicate that microRNAs (miRNAs) play an important role in regulating cellular quiescence. Our recent publication demonstrated the existence of an alternative miRNA biogenesis pathway in primary human foreskin fibroblast (HFF) cells during quiescence. Indeed, we have identified a group of pri-miRNAs (whose mature miRNAs were found induced during quiescence) modified with a 2,2,7-trimethylguanosine (TMG)-cap by the trimethylguanosine synthase 1 (TGS1) protein and transported to the cytoplasm by the Exportin-1 (XPO1) protein. We used an antibody against (TMG)-caps (which does not cross-react with the (m 7 G)-caps that most pri-miRNAs or mRNAs contain [Luhrmann et al ., 1982]) to perform RNA immunoprecipitations from total RNA extracts of proliferating or quiescent HFFs. The novelty of this assay is the specific isolation of pri-miRNAs as well as other non-coding RNAs containing a TMG-cap modification.
The Arabidopsis eukaryotic initiation factor (iso)4E is dispensable for plant growth but required for susceptibility to potyviruses.

Science.gov (United States)

Duprat, Anne; Caranta, Carole; Revers, Frédéric; Menand, Benoît; Browning, Karen S; Robaglia, Christophe

2002-12-01

An Arabidopsis thaliana line bearing a transposon insertion in the gene coding for the isozyme form of the plant-specific cap-binding protein, eukaryotic initiation factor (iso) 4E (eIF (iso) 4E), has been isolated. This mutant line completely lacks both eIF(iso)4E mRNA and protein, but was found to have a phenotype and fertility indistinguishable from wild-type plants under standard laboratory conditions. In contrast, the amount of the related eIF4E protein was found to increase in seedling extracts. Furthermore, polysome analysis shows that the mRNA encoding eIF4E was being translated at increased levels. Given the known interaction between cap-binding proteins and potyviral genome-linked proteins (VPg), this plant line was challenged with two potyviruses, Turnip mosaic virus (TuMV) and Lettuce mosaic virus (LMV) and was found resistant to both, but not to the Nepovirus, Tomato black ring virus (TBRV) and the Cucumovirus, Cucumber mosaic virus (CMV). Together with previous data showing that the VPg-eIF4E interaction is necessary for virus infectivity and upregulates genome amplification, this shows that the eIF4E proteins are specifically recruited for the replication cycle of potyviruses.
On Interactive Teaching Model of Translation Course Based on Wechat

Science.gov (United States)

Lin, Wang

2017-01-01

Constructivism is a theory related to knowledge and learning, focusing on learners' subjective initiative, based on which the interactive approach has been proved to play a crucial role in language learning. Accordingly, the interactive approach can also be applied to translation teaching since translation itself is a bilingual transformational…
ATLAS end-caps  on the move

CERN Multimedia

2007-01-01

Two delicate and spectacular transport operations have been performed for ATLAS in recent weeks: the first end-cap tracker was installed in its final position, and one of the huge end-caps of the toroid magnet was moved to the top of the experiment’s shaft.
CAPS OpenACC Compilers: Performance and Portability

CERN Multimedia

CERN. Geneva

2013-01-01

The announcement late 2011 of the new OpenACC directive-based programming standard supported by CAPS, CRAY and PGI compilers has open up the door to more scientific applications that can be ported on many-core systems. Following a porting methodology, this talk will first review the principles of programming with OpenACC and then the advanced features available in the CAPS compilers to further optimize OpenACC applications: library integration, tuning directives with auto-tune mechanisms to build applications adaptive to different GPUs. CAPS compilers use hardware vendors' backends such as NVIDIA CUDA and OpenCL making them the only OpenACC compilers supporting various many-core architectures. About the speaker Stéphane Bihan is co-funder and currently Director of Sales and Marketing at CAPS enterprise. He has held several R&D positions in companies such as ARC international plc in London, Canon Research Center France, ACE compiler experts in Amsterdam and the INRIA r...

Evaluation of strain in GaN/AlN quantum dots by means of resonant Raman scattering: the effect of capping

Energy Technology Data Exchange (ETDEWEB)

Cros, A.; Budagosky, J.A.; Garro, N.; Cantarero, A. [Institut de Ciencia del Materials, Universitat de Valencia, 46071 Valencia (Spain); Coraux, J.; Renevier, H.; Favre-Nicolin, V. [CEA-CNRS Group, ' ' Nanophysique et Semiconducteurs' ' , DRFMC/SP2M/PSC, CEA-Grenoble, 17 rue des Martyrs, 38054 Grenoble cedex 9 (France); Universite Joseph Fourier, BP 53, 38041 Grenoble Cedex 9 (France); Proietti, M.G. [Departamento de Fisica de la Materia Condensada, Instituto de Ciencia de Materiales de Aragon, CSIC-Universidad de Zaragoza, calle Pedro Cerbuna 12, 50009 Zaragoza (Spain); Daudin, B. [CEA-CNRS Group, ' ' Nanophysique et Semiconducteurs' ' , DRFMC/SP2M/PSC, CEA-Grenoble, 17 rue des Martyrs, 38054 Grenoble cedex 9 (France)

2007-06-15

We have studied in detail changes in the strain state of GaN/AlN quantum dots during the capping process. {mu}-Raman scattering experiments allowed the detection of a resonant mode which provided information on the evolution of strain with capping. Simultaneously, Multiwavelength Anomalous Diffraction (MAD) and Diffraction Anomalous Fine Structure (DAFS) experiments were performed on the same samples, providing the independent determination of the wurtzite lattice parameters a and c. The remarkable agreement between Raman and X-ray data stands out the suitability of polar vibrational modes for the determination of strain in nanostructures. (copyright 2007 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)
Generating efficiency: The power of price caps in the public and private Spanish electricity sectors

International Nuclear Information System (INIS)

Arocena, P.; Price, C.W.

1999-01-01

Economic regulation of firms with market power has placed increasing emphasis on incentive-based regulation such as price caps. The move to such regulation often coincides with a change of ownership, making it difficult to separate the incentive effects. We focus on the effect of regulation alone by analysing the imposition of price cap type regulation on both publicly and privately owned Spanish electricity generators in 1988, several years before three was any change of ownership. Our initial results indicate that the publicly owned generators are generally more efficient than the private ones, but that the effect of price caps is to increase the efficiency of private sector plants faster than those in the public sector. We introduce two novelties into the analysis: we incorporate levels of CO2 and NOx emissions; and we include declared plant availability as an output. The outcome is dependent on the choice of inputs and outputs, and we argue that our measures are more appropriate than traditional measures for a system of central despatch for generators facing environmental constraints. (au) 37 refs
Wind blade spar cap and method of making

Science.gov (United States)

Mohamed, Mansour H [Raleigh, NC

2008-05-27

A wind blade spar cap for strengthening a wind blade including an integral, unitary three-dimensional woven material having a first end and a second end, corresponding to a root end of the blade and a tip end of the blade, wherein the material tapers in width from the first to the second end while maintaining a constant thickness and decreasing weight therebetween, the cap being capable of being affixed to the blade for providing increased strength with controlled variation in weight from the root end to the tip end based upon the tapered width of the material thereof. The present inventions also include the method of making the wind blade spar cap and a wind blade including the wind blade spar cap.
Translation of field-reversed configurations in the FRX C/T experiment

Energy Technology Data Exchange (ETDEWEB)

Rej, D.J.; Armstrong, W.T.; Chrien, R.E.; Klingner, P.L.; Linford, R.K.; McKenna, K.F.; Milroy, R.D.; Sherwood, E.G.; Siemon, R.E.; Tuszewski, M.

1984-01-01

One of the unique features inherent to compact toroids is the potential ability to translate the plasma along its geometric axis. CT translation has proven useful in reactor design studies, and has been the focus of several experimental investigations. In this paper, we report on the initial results from translation experiments performed with the field-reversed configuration (FRC) plasmas generated in the FRX-C/T device.
Translation of field-reversed configurations in the FRX C/T experiment

International Nuclear Information System (INIS)

Rej, D.J.; Armstrong, W.T.; Chrien, R.E.

1984-01-01

One of the unique features inherent to compact toroids is the potential ability to translate the plasma along its geometric axis. CT translation has proven useful in reactor design studies, and has been the focus of several experimental investigations. In this paper, we report on the initial results from translation experiments performed with the field-reversed configuration (FRC) plasmas generated in the FRX-C/T device
State-of-the-art synthetic membrane for capping landfills

International Nuclear Information System (INIS)

Kriofske, K.P.; Gagle, D.W.

1991-01-01

Very Low Density Polyethylene (VLDPE) has emerged as a superior capping material for landfill closures. Landfills must be capped by a material which will undergo substantial deformation in areas of localized settlement prior to rupture. Methane and hydrogen sulfide gases must be contained and directed to collection points without permeating the landfill cap. Vegetative growth in the cover sods will be protected by the gas impermeability of the geosynthetic membrane. VLDPE compounded with carbon black is minimally affected by radiation and is inert to ultraviolet rays. This property sustains VLDPE's ability to retard gas permeation at levels superior to other geosynthetics. Cover soil stability on long cap slopes in all weather conditions is crucial. It has been demonstrated in the laboratory and in full-scale, on-site test conditions that VLDPE exhibits friction characteristics equaling or exceeding other synthetics used for this purpose without diminishing physical and chemical properties. Large-scale, multiaxial stress tests have demonstrated the ability of VLDPE to deflect substantially in all directions of a potential settlement area. Only PVC can equal the elastic deformation properties of VLDPE, but PVC is more gas-permeable susceptible to degradation due to natural soil radiation or ultraviolet light and heat. Test results are presented to illustrate these points. The geosynthetic cap membrane must prevent water percolation into the landfill to prevent the formation of hazardous leachates. The use of a VLDPE cap reduces the depth of cap soils, thus increasing landfill volume. The economics and reduction in long-term liabilities of closure costs are enhanced by the use of VLDPE in the cap system. Since the expected half-life of polyethylene exceeds hundreds of years, the inclusion of VLDPE in the cap system will provide pollution security for many generations
NATIONAL FRAMEWORK FOR THE SUSTAINABILITY OF HEALTH KNOWLEDGE TRANSLATION INITIATIVES IN UGANDA.

Science.gov (United States)

Basaza, Robert; Kinegyere, Alison; Mutatina, Boniface; Sewankambo, Nelson

2018-01-01

The aim of this study was to provide evidence about the design and implementation of policies for advancing the sustainability of knowledge translation (KT) initiatives and policies in Uganda's health system. We searched for and reviewed evidence about KT sustainability issues in Uganda, the impacts of options, barriers to implementing these options, and implementation strategies to address such barriers. In instances where the systematic reviews provided limited evidence, these were supplemented with relevant primary studies. Documents such as the government reports and unpublished literature were also included in the search. Key informant interviews and a policy dialogue were conducted, and an expert working group guided the study. The KT sustainability issues identified were: the absence of a specific unit within the health sector to coordinate and synthesize research; health worker not familiar with KT activities and not often used. Furthermore, Uganda lacks a mechanism to sustain its current national health frameworks or platforms, and does not have a system to ensure the sustained coordination of existing national health KT platforms. The policy options proposed include: (i) the identification of a KT champion; (ii) the establishment of an operational KT framework; (iii) KT capacity building for researchers and research users, as well as policy and decision makers. The sustainability of KT will be influenced by the prevailing context and concerns within healthcare both in Uganda and internationally. Furthermore, the availability of resources for KT advocacy, communication, and program design will impact on the sustainability of Uganda's KT activities.
Deciphering the Translation Initiation Factor 5A Modification Pathway in Halophilic Archaea

Directory of Open Access Journals (Sweden)

Laurence Prunetti

2016-01-01

Full Text Available Translation initiation factor 5A (IF5A is essential and highly conserved in Eukarya (eIF5A and Archaea (aIF5A. The activity of IF5A requires hypusine, a posttranslational modification synthesized in Eukarya from the polyamine precursor spermidine. Intracellular polyamine analyses revealed that agmatine and cadaverine were the main polyamines produced in Haloferax volcanii in minimal medium, raising the question of how hypusine is synthesized in this halophilic Archaea. Metabolic reconstruction led to a tentative picture of polyamine metabolism and aIF5A modification in Hfx. volcanii that was experimentally tested. Analysis of aIF5A from Hfx. volcanii by LC-MS/MS revealed it was exclusively deoxyhypusinylated. Genetic studies confirmed the role of the predicted arginine decarboxylase gene (HVO_1958 in agmatine synthesis. The agmatinase-like gene (HVO_2299 was found to be essential, consistent with a role in aIF5A modification predicted by physical clustering evidence. Recombinant deoxyhypusine synthase (DHS from S. cerevisiae was shown to transfer 4-aminobutyl moiety from spermidine to aIF5A from Hfx. volcanii in vitro. However, at least under conditions tested, this transfer was not observed with the Hfx. volcanii DHS. Furthermore, the growth of Hfx. volcanii was not inhibited by the classical DHS inhibitor GC7. We propose a model of deoxyhypusine synthesis in Hfx. volcanii that differs from the canonical eukaryotic pathway, paving the way for further studies.
Integrating Bioethics into Clinical and Translational Science Research: A Roadmap

Science.gov (United States)

Shapiro, Robyn S.; Layde, Peter M.

2008-01-01

Abstract Recent initiatives to improve human health emphasize the need to effectively and appropriately translate new knowledge gleaned from basic biomedical and behavioral research to clinical and community application. To maximize the beneficial impact of scientific advances in clinical practice and community health, and to guard against potential deleterious medical and societal consequences of such advances, incorporation of bioethics at each stage of clinical and translational science research is essential. At the earliest stage, bioethics input is critical to address issues such as whether to limit certain areas of scientific inquiry. Subsequently, bioethics input is important to assure not only that human subjects trials are conducted and reported responsibly, but also that results are incorporated into clinical and community practices in a way that promotes and protects bioethical principles. At the final stage of clinical and translational science research, bioethics helps to identify the need and approach for refining clinical practices when safety or other concerns arise. The framework we present depicts how bioethics interfaces with each stage of clinical and translational science research, and suggests an important research agenda for systematically and comprehensively assuring bioethics input into clinical and translational science initiatives. PMID:20443821
Matrix vesicles in the fibrous cap of atherosclerotic plaque: possible contribution to plaque rupture.

Science.gov (United States)

Bobryshev, Y V; Killingsworth, M C; Lord, R S A; Grabs, A J

2008-10-01

Plaque rupture is the most common type of plaque complication and leads to acute ischaemic events such as myocardial infarction and stroke. Calcification has been suggested as a possible indicator of plaque instability. Although the role of matrix vesicles in the initial stages of arterial calcification has been recognized, no studies have yet been carried out to examine a possible role of matrix vesicles in plaque destabilization. Tissue specimens selected for the present study represented carotid specimens obtained from patients undergoing carotid endarterectomy. Serial frozen cross-sections of the tissue specimens were cut and mounted on glass slides. The thickness of the fibrous cap (FCT) in each advanced atherosclerotic lesion, containing a well developed lipid/necrotic core, was measured at its narrowest sites in sets of serial sections. According to established criteria, atherosclerotic plaque specimens were histologically subdivided into two groups: vulnerable plaques with thin fibrous caps (FCT <100 microm) and presumably stable plaques, in which fibrous caps were thicker than 100 microm. Twenty-four carotid plaques (12 vulnerable and 12 presumably stable plaques) were collected for the present analysis of matrix vesicles in fibrous caps. In order to provide a sufficient number of representative areas from each plaque, laser capture microdissection (LCM) was carried out. The quantification of matrix vesicles in ultrathin sections of vulnerable and stable plaques revealed that the numbers of matrix vesicles were significantly higher in fibrous caps of vulnerable plaques than those in stable plaques (8.908+0.544 versus 6.208+0.467 matrix vesicles per 1.92 microm2 standard area; P= 0.0002). Electron microscopy combined with X-ray elemental microanalysis showed that some matrix vesicles in atherosclerotic plaques were undergoing calcification and were characterized by a high content of calcium and phosphorus. The percentage of calcified matrix vesicles
The eIF4E-binding proteins are modifiers of cytoplasmic eIF4E relocalization during the heat shock response

OpenAIRE

Sukarieh, R.; Sonenberg, N.; Pelletier, J.

2009-01-01

Stress granules (SGs) arise as a consequence of cellular stress, contain stalled translation preinitiation complexes, and are associated with cell survival during environmental insults. SGs are dynamic entities with proteins relocating into and out of them during stress. Among the repertoire of proteins present in SGs is eukaryotic initiation factor 4E (eIF4E), a translation factor required for cap-dependent translation and that regulates a rate-limiting step for protein synthesis. Herein, we...
Understanding Translation

DEFF Research Database (Denmark)

Schjoldager, Anne Gram; Gottlieb, Henrik; Klitgård, Ida

Understanding Translation is designed as a textbook for courses on the theory and practice of translation in general and of particular types of translation - such as interpreting, screen translation and literary translation. The aim of the book is to help you gain an in-depth understanding...... of the phenomenon of translation and to provide you with a conceptual framework for the analysis of various aspects of professional translation. Intended readers are students of translation and languages, but the book will also be relevant for others who are interested in the theory and practice of translation...... - translators, language teachers, translation users and literary, TV and film critics, for instance. Discussions focus on translation between Danish and English....
Truncated Dual-Cap Nucleation Site Development

Science.gov (United States)

Matson, Douglas M.; Sander, Paul J.

2012-01-01

During heterogeneous nucleation within a metastable mushy-zone, several geometries for nucleation site development must be considered. Traditional spherical dual cap and crevice models are compared to a truncated dual cap to determine the activation energy and critical cluster growth kinetics in ternary Fe-Cr-Ni steel alloys. Results of activation energy results indicate that nucleation is more probable at grain boundaries within the solid than at the solid-liquid interface.
Standard and alternative landfill capping design in Germany

International Nuclear Information System (INIS)

Simon, Franz-Georg; Mueller, Werner W.

2004-01-01

Engineered capping systems are in most cases an indispensable and often the only efficient component required by the long-term safety concept for landfills, mine tailings tips and contaminated land. In Germany the composite liner is the main component of standard landfill cappings for municipal and hazardous waste landfills and the compacted clay liner (CCL) for landfills for inert or low-contamination waste. The composite liner is a technically highly effective but very expensive system. Research and experience has given rise to concern about the proper long-term performance of a conventional single CCL as a landfill capping. Therefore, alternative capping systems are discussed and applied for landfills and for the containment of contaminated sites. This paper gives an overview on various alternative engineered cappings and suitable systems for capping reflecting the state of the art and the expert view in Germany. According to the European Council Directive on the landfill of waste an impermeable mineral layer is recommended for the surface sealing of non-hazardous landfills and a composition of artificial sealing liner and impermeable mineral layer for hazardous landfills. In both cases a drainage layer thickness of at least 0.5 m is suggested. These recommendations should be interpreted flexibly and to some extent modified in the light of the experience and results presented in this paper
Clean translation of an imperative reversible programming language

DEFF Research Database (Denmark)

Axelsen, Holger Bock

2011-01-01

We describe the translation techniques used for the code generation in a compiler from the high-level reversible imperative programming language Janus to the low-level reversible assembly language PISA. Our translation is both semantics preserving (correct), in that target programs compute exactly...... the same functions as their source programs (cleanly, with no extraneous garbage output), and efficient, in that target programs conserve the complexities of source programs. In particular, target programs only require a constant amount of temporary garbage space. The given translation methods are generic......, and should be applicable to any (imperative) reversible source language described with reversible flowcharts and reversible updates. To our knowledge, this is the first compiler between reversible languages where the source and target languages were independently developed; the first exhibiting both...
LPS injection reprograms the expression and the 3' UTR of a CAP gene by alternative polyadenylation and the formation of a GAIT element in Ciona intestinalis.

Science.gov (United States)

Vizzini, Aiti; Bonura, Angela; Longo, Valeria; Sanfratello, Maria Antonietta; Parrinello, Daniela; Cammarata, Matteo; Colombo, Paolo

2016-09-01

The diversification of cellular functions is one of the major characteristics of multicellular organisms which allow cells to modulate their gene expression, leading to the formation of transcripts and proteins with different functions and concentrations in response to different stimuli. CAP genes represent a widespread family of proteins belonging to the cysteine-rich secretory protein, antigen 5 and pathogenesis-related 1 superfamily which, it has been proposed, play key roles in the infection process and the modulation of immune responses in host animals. The ascidian Ciona intestinalis represents a group of proto-chordates with an exclusively innate immune system that has been widely studied in the field of comparative and developmental immunology. Using this biological system, we describe the identification of a novel APA mechanism by which an intronic polyadenylation signal is activated by LPS injection, leading to the formation of a shorter CAP mRNA capable of expressing the first CAP exon plus 19 amino acid residues whose sequence is contained within the first intron of the annotated gene. Furthermore, such an APA event causes the expression of a translational controlling cis-acting GAIT element which is not present in the previously isolated CAP isoform and identified in the 3'-UTR of other immune-related genes, suggesting an intriguing scenario in which both transcriptional and post-transcriptional control mechanisms are involved in the activation of the CAP gene during inflammatory response in C. intestinalis. Copyright © 2016 Elsevier Ltd. All rights reserved.
International and national initiatives in biobanking.

Science.gov (United States)

Ectors, N

2011-01-01

Translational research and biobanking are "in", also in Flanders and in Belgium. In Flanders the Advice report 120 from the Flemish Council for Science and innovation, entitled "Extension of translational research in Flanders" paved the way for the Center for Medical Innovation. The Center for Medical Innovation aims at promoting collaboration between Flemish Universities, university hospitals, pharma and biotech industry and the Flemish Government specifically in the domain of translational research. The Initiative # 27 of the Cancer plan from the Federal Government aims at financing a virtual interuniversity tumor bank in order to promote "cancer" translational research in a collaborative network between academic structures, general hospitals en different industrial partners (pharmacy, biotechnology, diagnostics, ...) active in research in Belgium. However, the scientific interest in the human tissues is not new, at all. This text aims at giving an overview of the development and evolutions of "biobanking" initiatives.
Temperature Distribution within a Cold Cap during Nuclear Waste Vitrification.

Science.gov (United States)

Dixon, Derek R; Schweiger, Michael J; Riley, Brian J; Pokorny, Richard; Hrma, Pavel

2015-07-21

The kinetics of the feed-to-glass conversion affects the waste vitrification rate in an electric glass melter. The primary area of interest in this conversion process is the cold cap, a layer of reacting feed on top of the molten glass. The work presented here provides an experimental determination of the temperature distribution within the cold cap. Because direct measurement of the temperature field within the cold cap is impracticable, an indirect method was developed in which the textural features in a laboratory-made cold cap with a simulated high-level waste feed were mapped as a function of position using optical microscopy, scanning electron microscopy, energy dispersive spectroscopy, and X-ray diffraction. The temperature distribution within the cold cap was established by correlating microstructures of cold-cap regions with heat-treated feed samples of nearly identical structures at known temperatures. This temperature profile was compared with a mathematically simulated profile generated by a cold-cap model that has been developed to assess the rate of glass production in a melter.
20 CFR 606.21 - Criteria for cap.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Criteria for cap. 606.21 Section 606.21 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR TAX CREDITS UNDER THE... Reduction § 606.21 Criteria for cap. (a) Reduction in unemployment tax effort. (1) For purposes of paragraph...
Development of CAP code for nuclear power plant containment: Lumped model

Energy Technology Data Exchange (ETDEWEB)

Hong, Soon Joon, E-mail: sjhong90@fnctech.com [FNC Tech. Co. Ltd., Heungdeok 1 ro 13, Giheung-gu, Yongin-si, Gyeonggi-do 446-908 (Korea, Republic of); Choo, Yeon Joon; Hwang, Su Hyun; Lee, Byung Chul [FNC Tech. Co. Ltd., Heungdeok 1 ro 13, Giheung-gu, Yongin-si, Gyeonggi-do 446-908 (Korea, Republic of); Ha, Sang Jun [Central Research Institute, Korea Hydro & Nuclear Power Company, Ltd., 70, 1312-gil, Yuseong-daero, Yuseong-gu, Daejeon 305-343 (Korea, Republic of)

2015-09-15

Highlights: • State-of-art containment analysis code, CAP, has been developed. • CAP uses 3-field equations, water level oriented upwind scheme, local head model. • CAP has a function of linked calculation with reactor coolant system code. • CAP code assessments showed appropriate prediction capabilities. - Abstract: CAP (nuclear Containment Analysis Package) code has been developed in Korean nuclear society for the analysis of nuclear containment thermal hydraulic behaviors including pressure and temperature trends and hydrogen concentration. Lumped model of CAP code uses 2-phase, 3-field equations for fluid behaviors, and has appropriate constitutive equations, 1-dimensional heat conductor model, component models, trip and control models, and special process models. CAP can run in a standalone mode or a linked mode with a reactor coolant system analysis code. The linked mode enables the more realistic calculation of a containment response and is expected to be applicable to a more complicated advanced plant design calculation. CAP code assessments were carried out by gradual approaches: conceptual problems, fundamental phenomena, component and principal phenomena, experimental validation, and finally comparison with other code calculations on the base of important phenomena identifications. The assessments showed appropriate prediction capabilities of CAP.

Development of CAP code for nuclear power plant containment: Lumped model

International Nuclear Information System (INIS)

Hong, Soon Joon; Choo, Yeon Joon; Hwang, Su Hyun; Lee, Byung Chul; Ha, Sang Jun

2015-01-01

Highlights: • State-of-art containment analysis code, CAP, has been developed. • CAP uses 3-field equations, water level oriented upwind scheme, local head model. • CAP has a function of linked calculation with reactor coolant system code. • CAP code assessments showed appropriate prediction capabilities. - Abstract: CAP (nuclear Containment Analysis Package) code has been developed in Korean nuclear society for the analysis of nuclear containment thermal hydraulic behaviors including pressure and temperature trends and hydrogen concentration. Lumped model of CAP code uses 2-phase, 3-field equations for fluid behaviors, and has appropriate constitutive equations, 1-dimensional heat conductor model, component models, trip and control models, and special process models. CAP can run in a standalone mode or a linked mode with a reactor coolant system analysis code. The linked mode enables the more realistic calculation of a containment response and is expected to be applicable to a more complicated advanced plant design calculation. CAP code assessments were carried out by gradual approaches: conceptual problems, fundamental phenomena, component and principal phenomena, experimental validation, and finally comparison with other code calculations on the base of important phenomena identifications. The assessments showed appropriate prediction capabilities of CAP
Survey of Enabling Technologies for CAPS

Science.gov (United States)

Antol, Jeffrey; Mazanek, Daniel D.; Koons, Robert H.

2005-01-01

The enabling technologies required for the development of a viable Comet/Asteroid Protection System (CAPS) can be divided into two principal areas: detection and deflection/orbit modification. With the proper funding levels, many of the technologies needed to support a CAPS architecture could be achievable within the next 15 to 20 years. In fact, many advanced detection technologies are currently in development for future in-space telescope systems such as the James Webb Space Telescope (JWST), formerly known as the Next Generation Space Telescope. It is anticipated that many of the JWST technologies would be available for application for CAPS detection concepts. Deflection/orbit modification technologies are also currently being studied as part of advanced power and propulsion research. However, many of these technologies, such as extremely high-output power systems, advanced propulsion, heat rejection, and directed energy systems, would likely be farther term in availability than many of the detection technologies. Discussed subsequently is a preliminary examination of the main technologies that have been identified as being essential to providing the element functionality defined during the CAPS conceptual study. The detailed requirements for many of the technology areas are still unknown, and many additional technologies will be identified as future in-depth studies are conducted in this area.
NASA-IGES Translator and Viewer

Science.gov (United States)

Chou, Jin J.; Logan, Michael A.

1995-01-01

NASA-IGES Translator (NIGEStranslator) is a batch program that translates a general IGES (Initial Graphics Exchange Specification) file to a NASA-IGES-Nurbs-Only (NINO) file. IGES is the most popular geometry exchange standard among Computer Aided Geometric Design (CAD) systems. NINO format is a subset of IGES, implementing the simple and yet the most popular NURBS (Non-Uniform Rational B-Splines) representation. NIGEStranslator converts a complex IGES file to the simpler NINO file to simplify the tasks of CFD grid generation for models in CAD format. The NASA-IGES Viewer (NIGESview) is an Open-Inventor-based, highly interactive viewer/ editor for NINO files. Geometry in the IGES files can be viewed, copied, transformed, deleted, and inquired. Users can use NIGEStranslator to translate IGES files from CAD systems to NINO files. The geometry then can be examined with NIGESview. Extraneous geometries can be interactively removed, and the cleaned model can be written to an IGES file, ready to be used in grid generation.
Plant Translation Factors and Virus Resistance

Directory of Open Access Journals (Sweden)

Hélène Sanfaçon

2015-06-01

Full Text Available Plant viruses recruit cellular translation factors not only to translate their viral RNAs but also to regulate their replication and potentiate their local and systemic movement. Because of the virus dependence on cellular translation factors, it is perhaps not surprising that many natural plant recessive resistance genes have been mapped to mutations of translation initiation factors eIF4E and eIF4G or their isoforms, eIFiso4E and eIFiso4G. The partial functional redundancy of these isoforms allows specific mutation or knock-down of one isoform to provide virus resistance without hindering the general health of the plant. New possible targets for antiviral strategies have also been identified following the characterization of other plant translation factors (eIF4A-like helicases, eIF3, eEF1A and eEF1B that specifically interact with viral RNAs and proteins and regulate various aspects of the infection cycle. Emerging evidence that translation repression operates as an alternative antiviral RNA silencing mechanism is also discussed. Understanding the mechanisms that control the development of natural viral resistance and the emergence of virulent isolates in response to these plant defense responses will provide the basis for the selection of new sources of resistance and for the intelligent design of engineered resistance that is broad-spectrum and durable.
Splicing of goose parvovirus pre-mRNA influences cytoplasmic translation of the processed mRNA

Energy Technology Data Exchange (ETDEWEB)

Li, Long; Pintel, David J., E-mail: pinteld@missouri.edu

2012-04-25

Translation of goose parvovirus (GPV) 72 kDa Rep 1 is initiated from unspliced P9-generated mRNAs in ORF1 from the first in-frame AUG (537 AUG); however, this AUG is bypassed in spliced P9-generated RNA: translation of the 52 kDa Rep 2 protein from spliced RNA is initiated in ORF2 at the next AUG downstream (650 AUG). Usage of the 537 AUG was restored in spliced RNA when the GPV intron was replaced with a chimeric SV40 intron, or following specific mutations of the GPV intron which did not appear in the final spliced mRNA. Additionally, 650 AUG usage was gained in unspliced RNA when the GPV intron splice sites were debilitated. Splicing-dependent regulation of translation initiation was mediated in cis by GPV RNA surrounding the target AUGs. Thus, nuclear RNA processing of GPV P9-generated pre-mRNAs has a complex, but significant, effect on alternative translation initiation of the GPV Rep proteins.
Splicing of goose parvovirus pre-mRNA influences cytoplasmic translation of the processed mRNA

International Nuclear Information System (INIS)

Li, Long; Pintel, David J.

2012-01-01

Translation of goose parvovirus (GPV) 72 kDa Rep 1 is initiated from unspliced P9-generated mRNAs in ORF1 from the first in-frame AUG (537 AUG); however, this AUG is bypassed in spliced P9-generated RNA: translation of the 52 kDa Rep 2 protein from spliced RNA is initiated in ORF2 at the next AUG downstream (650 AUG). Usage of the 537 AUG was restored in spliced RNA when the GPV intron was replaced with a chimeric SV40 intron, or following specific mutations of the GPV intron which did not appear in the final spliced mRNA. Additionally, 650 AUG usage was gained in unspliced RNA when the GPV intron splice sites were debilitated. Splicing-dependent regulation of translation initiation was mediated in cis by GPV RNA surrounding the target AUGs. Thus, nuclear RNA processing of GPV P9-generated pre-mRNAs has a complex, but significant, effect on alternative translation initiation of the GPV Rep proteins.
CMS end-cap yoke at the detector's assembly site.

CERN Multimedia

Patrice Loïez

2002-01-01

The magnetic flux generated by the superconducting coil in the CMS detector is returned via an iron yoke comprising three end-cap discs at each end (end-cap yoke) and five concentric cylinders (barrel yoke). This picture shows the first of three end-cap discs (red) seen through the outer cylinder of the vacuum tank which will house the superconducting coil.
Impact Response Study on Covering Cap of Aircraft Big-Size Integral Fuel Tank

Science.gov (United States)

Wang, Fusheng; Jia, Senqing; Wang, Yi; Yue, Zhufeng

2016-10-01

In order to assess various design concepts and choose a kind of covering cap design scheme which can meet the requirements of airworthiness standard and ensure the safety of fuel tank. Using finite element software ANSYS/LS- DYNA, the impact process of covering cap of aircraft fuel tank by projectile were simulated, in which dynamical characteristics of simple single covering cap and gland double-layer covering cap impacted by titanium alloy projectile and rubber projectile were studied, as well as factor effects on simple single covering cap and gland double-layer covering cap under impact region, impact angle and impact energy were also studied. Though the comparison of critical damage velocity and element deleted number of the covering caps, it shows that the external covering cap has a good protection effect on internal covering cap. The regions close to boundary are vulnerable to appear impact damage with titanium alloy projectile while the regions close to center is vulnerable to occur damage with rubber projectile. Equivalent strain in covering cap is very little when impact angle is less than 15°. Element deleted number in covering cap reaches the maximum when impact angle is between 60°and 65°by titanium alloy projectile. While the bigger the impact angle and the more serious damage of the covering cap will be when rubber projectile impact composite covering cap. The energy needed for occurring damage on external covering cap and internal covering cap is less than and higher than that when single covering cap occur damage, respectively. The energy needed for complete breakdown of double-layer covering cap is much higher than that of single covering cap.
Facially amphiphilic thiol capped gold and silver nanoparticles

Indian Academy of Sciences (India)

Abstract. A series of bile acid-derived facially amphiphilic thiols have been used to cap sliver and gold nanoparticles. The self-assembling properties of these steroid-capped nanoparticles have been investigated and reported in this article.
CAPS Activity in Priming Vesicle Exocytosis Requires CK2 Phosphorylation*

OpenAIRE

Nojiri, Mari; Loyet, Kelly M.; Klenchin, Vadim A.; Kabachinski, Gregory; Martin, Thomas F. J.

2009-01-01

CAPS (Ca2+-dependent activator protein for secretion) functions in priming Ca2+-dependent vesicle exocytosis, but the regulation of CAPS activity has not been characterized. Here we show that phosphorylation by protein kinase CK2 is required for CAPS activity. Dephosphorylation eliminated CAPS activity in reconstituting Ca2+-dependent vesicle exocytosis in permeable and intact PC12 cells. Ser-5, -6, and -7 and Ser-1281 were identified by mass spectrometry as the major phosphorylation sites in...
The histone deacetylase inhibitor, Vorinostat, represses hypoxia inducible factor 1 alpha expression through translational inhibition.

Directory of Open Access Journals (Sweden)

Darren M Hutt

Full Text Available Hypoxia inducible factor 1α (HIF-1α is a master regulator of tumor angiogenesis being one of the major targets for cancer therapy. Previous studies have shown that Histone Deacetylase Inhibitors (HDACi block tumor angiogenesis through the inhibition of HIF-1α expression. As such, Vorinostat (Suberoylanilide Hydroxamic Acid/SAHA and Romidepsin, two HDACis, were recently approved by the Food and Drug Administration (FDA for the treatment of cutaneous T cell lymphoma. Although HDACis have been shown to affect HIF-1α expression by modulating its interactions with the Hsp70/Hsp90 chaperone axis or its acetylation status, the molecular mechanisms by which HDACis inhibit HIF-1α expression need to be further characterized. Here, we report that the FDA-approved HDACi Vorinostat/SAHA inhibits HIF-1α expression in liver cancer-derived cell lines, by a new mechanism independent of p53, prolyl-hydroxylases, autophagy and proteasome degradation. We found that SAHA or silencing of HDAC9 mechanism of action is due to inhibition of HIF-1α translation, which in turn, is mediated by the eukaryotic translation initiation factor--eIF3G. We also highlighted that HIF-1α translation is dramatically inhibited when SAHA is combined with eIF3H silencing. Taken together, we show that HDAC activity regulates HIF-1α translation, with HDACis such as SAHA representing a potential novel approach for the treatment of hepatocellular carcinoma.
Sediment Capping and Natural Recovery, Contaminant Transport Fundamentals With Applications to Sediment Caps

National Research Council Canada - National Science Library

Petrovski, David M; Corcoran, Maureen K; May, James H; Patrick, David M

2005-01-01

Engineered sediment caps and natural recovery are in situ remedial alternatives for contaminated sediments, which consist of the artificial or natural placement of a layer of material over a sediment...
Landscape Evolution and the Reincarnation of the Southern Residual Ice Cap

Science.gov (United States)

Byrne, S.; Zuber, M. T.

2006-10-01

Given the present rate of erosion on the southern residual ice cap, it is unlikely that any part of the cap is older than a few centuries. Unless we're lucky, why is there a residual cap present today for us to observe? We propose a solution involving constant destruction and renewal of the cap.
Analyses of Current And Wave Forces on Velocity Caps

DEFF Research Database (Denmark)

Christensen, Erik Damgaard; Buhrkall, Jeppe; Eskesen, Mark C. D.

2015-01-01

Velocity caps are often used in connection with for instance offshore intake sea water for the use of for cooling water for power plants or as a source for desalinization plants. The intakes can also be used for river intakes. The velocity cap is placed on top of a vertical pipe. The vertical pipe......) this paper investigates the current and wave forces on the velocity cap and the vertical cylinder. The Morison’s force model was used in the analyses of the extracted force time series in from the CFD model. Further the distribution of the inlet velocities around the velocity cap was also analyzed in detail...
Development, genetic mapping and QTL association of cotton PHYA, PHYB, and HY5-specific CAPS and dCAPS markers

Science.gov (United States)

Among SNP markers that become increasingly valuable in molecular breeding of crop plants are the CAP and dCAP markers derived from the genes of interest. To date, the number of such gene-based markers is small in polyploid crop plants such as tetraploid cotton that has A and D subgenomes. The obje...
Preventing Thin Film Dewetting via Graphene Capping.

Science.gov (United States)

Cao, Peigen; Bai, Peter; Omrani, Arash A; Xiao, Yihan; Meaker, Kacey L; Tsai, Hsin-Zon; Yan, Aiming; Jung, Han Sae; Khajeh, Ramin; Rodgers, Griffin F; Kim, Youngkyou; Aikawa, Andrew S; Kolaczkowski, Mattew A; Liu, Yi; Zettl, Alex; Xu, Ke; Crommie, Michael F; Xu, Ting

2017-09-01

A monolayer 2D capping layer with high Young's modulus is shown to be able to effectively suppress the dewetting of underlying thin films of small organic semiconductor molecule, polymer, and polycrystalline metal, respectively. To verify the universality of this capping layer approach, the dewetting experiments are performed for single-layer graphene transferred onto polystyrene (PS), semiconducting thienoazacoronene (EH-TAC), gold, and also MoS 2 on PS. Thermodynamic modeling indicates that the exceptionally high Young's modulus and surface conformity of 2D capping layers such as graphene and MoS 2 substantially suppress surface fluctuations and thus dewetting. As long as the uncovered area is smaller than the fluctuation wavelength of the thin film in a dewetting process via spinodal decomposition, the dewetting should be suppressed. The 2D monolayer-capping approach opens up exciting new possibilities to enhance the thermal stability and expands the processing parameters for thin film materials without significantly altering their physical properties. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Translational physiology: from molecules to public health.

Science.gov (United States)

Seals, Douglas R

2013-07-15

The term 'translational research' was coined 20 years ago and has become a guiding influence in biomedical research. It refers to a process by which the findings of basic research are extended to the clinical research setting (bench to bedside) and then to clinical practice and eventually health policy (bedside to community). It is a dynamic, multidisciplinary research approach. The concept of translational physiology applies the translational research model to the physiological sciences. It differs from the traditional areas of integrative and clinical physiology by its broad investigative scope of basic research to community health. Translational physiology offers exciting opportunities, but presently is under-developed and -utilized. A key challenge will be to expand physiological research by extending investigations to communities of patients and healthy (or at risk) individuals. This will allow bidirectional physiological investigation throughout the translational continuum: basic research observations can be studied up to the population level, and mechanisms can be assessed by 'reverse translation' in clinical research settings and preclinical models based on initial observations made in populations. Examples of translational physiology questions, experimental approaches, roadblocks and strategies for promotion are discussed. Translational physiology provides a novel framework for physiology programs and an investigational platform for physiologists to study function from molecular events to public health. It holds promise for enhancing the completeness and societal impact of our work, while further solidifying the critical role of physiology in the biomedical research enterprise.
Preform spar cap for a wind turbine rotor blade

Science.gov (United States)

Livingston, Jamie T [Simpsonville, SC; Driver, Howard D [Greer, SC; van Breugel, Sjef [Enschede, NL; Jenkins, Thomas B [Cantonment, FL; Bakhuis, Jan Willem [Nijverdal, NL; Billen, Andrew J [Daarlerveen, NL; Riahi, Amir [Pensacola, FL

2011-07-12

A spar cap for a wind turbine rotor blade. The spar cap may include multiple preform components. The multiple preform components may be planar sheets having a swept shape with a first end and a second end. The multiple preform components may be joined by mating the first end of a first preform component to the second end of a next preform component, forming the spar cap.
Effects of titanium surface anodization with CaP incorporation on human osteoblastic response

Science.gov (United States)

OLIVEIRA, Natássia Cristina Martins; MOURA, Camilla Christian Gomes; ZANETTA-BARBOSA, Darceny; MENDONÇA, Daniela Baccelli Silveira; MENDONÇA, Gustavo; DECHICHI, Paula

2015-01-01

In this study we investigated whether anodization with calcium phosphate (CaP) incorporation (Vulcano®) enhances growth factors secretion, osteoblast-specific gene expression, and cell viability, when compared to acid etched surfaces (Porous®) and machined surfaces (Screw®) after 3 and 7 days. Results showed significant cell viability for Porous and Vulcano at day 7, when compared with Screw (p=0.005). At the same time point, significant differences regarding runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and bone sialoprotein (BSP) expression were found for all surfaces (p0.05). Although no significant correlation was found for growth factors secretion and Runx2 expression, a significant positive correlation between this gene and ALP/BSP expression showed that their strong association is independent on the type of surface. The incorporation of CaP affected the biological parameters evaluated similar to surfaces just acid etched. The results presented here support the observations that roughness also may play an important role in determining cell response. PMID:23498218
ERK 1/2 kinase metabolic pathway is responsible for phosphorylation of translation initiation factor eIF4E during in vitro maturation of pig oocytes

Czech Academy of Sciences Publication Activity Database

Ellederová, Zdeňka; Cais, Ondřej; Šušor, Andrej; Uhlířová, Kateřina; Kovářová, Hana; Jelínková, Lucie; Tomek, W.; Kubelka, Michal

2008-01-01

Roč. 75, č. 2 (2008), s. 309-317 ISSN 1040-452X R&D Projects: GA ČR GA524/04/0104 Grant - others:Deutsche Forschungsgemeinschaft(DE) 463 TSE 113/28 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50110509 Keywords : meiosis * translation initiation * eIF4E Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.287, year: 2008

Genetic Algorithms for Models Optimization for Recognition of Translation Initiation Sites

KAUST Repository

Mora, Arturo Magana

2011-06-01

This work uses genetic algorithms (GA) to reduce the complexity of the artificial neural networks (ANNs) and decision trees (DTs) for the accurate recognition of translation initiation sites (TISs) in Arabidopsis Thaliana. The Arabidopsis data was extracted directly from genomic DNA sequences. Methods derived in this work resulted in both reduced complexity of the predictors, as well as in improvement in prediction accuracy (generalization). Optimization through use of GA is generally a computationally intensive task. One of the approaches to overcome this problem is to use parallelization of code that implements GA, thus allowing computation on multiprocessing infrastructure. However, further improvement in performance GA implementation could be achieved through modification done to GA basic operations such as selection, crossover and mutation. In this work we explored two such improvements, namely evolutive mutation and GA-Simplex crossover operation. In this thesis we studied the benefit of these modifications on the problem of TISs recognition. Compared to the non-modified GA approach, we reduced the number of weights in the resulting model\\'s neural network component by 51% and the number of nodes in the model\\'s DTs component by 97% whilst improving the model\\'s accuracy at the same time. Separately, we developed another methodology for reducing the complexity of prediction models by optimizing the composition of training data subsets in bootstrap aggregation (bagging) methodology. This optimization is achieved by applying a new GA-based bagging methodology in order to optimize the composition of each of the training data subsets. This approach has shown in our test cases to considerably enhance the accuracy of the TIS prediction model compared to the original bagging methodology. Although these methods are applied to the problem of accurate prediction of TISs we believe that these methodologies have a potential for wider scope of application.
Mapping Translation Technology Research in Translation Studies

DEFF Research Database (Denmark)

Schjoldager, Anne; Christensen, Tina Paulsen; Flanagan, Marian

2017-01-01

/Schjoldager 2010, 2011; Christensen 2011). Unfortunately, the increasing professional use of translation technology has not been mirrored within translation studies (TS) by a similar increase in research projects on translation technology (Munday 2009: 15; O’Hagan 2013; Doherty 2016: 952). The current thematic...... section aims to improve this situation by presenting new and innovative research papers that reflect on recent technological advances and their impact on the translation profession and translators from a diversity of perspectives and using a variety of methods. In Section 2, we present translation...... technology research as a subdiscipline of TS, and we define and discuss some basic concepts and models of the field that we use in the rest of the paper. Based on a small-scale study of papers published in TS journals between 2006 and 2016, Section 3 attempts to map relevant developments of translation...
Chemical synthesis of highly size-confined triethylamine-capped ...

Indian Academy of Sciences (India)

2018-03-23

Mar 23, 2018 ... TiO2 nanoparticles and its dye-sensitized solar cell performance .... Figure 5. Formation mechanism of TEA-capped and uncapped TiO2 nanoparticles. ... this research work, synthesized TEA-capped TiO2 nanopar- ticles were ...
Analysis of Dynamic Stiffness of Bridge Cap-Pile System

Directory of Open Access Journals (Sweden)

Jinhui Chu

2018-01-01

Full Text Available In order to investigate the applicability of dynamic stiffness for bridge cap-pile system, a laboratory test was performed. A numerical model was also built for this type of system. The impact load was applied on the cap top and the dynamic stiffness was analysed. Then, the effect of the effective friction area between pile and soil was also considered. Finally, the dynamic stiffness relationship between the single pile and the cap-pile system was also compared. The results show that the dynamic stiffness is a sensitive index and can well reflect the static characteristics of the pile at the elastic stage. There is a significant positive correlation between the vertical dynamic stiffness index and bearing capacity of the cap-pile system in the similar formation environment. For the cap-pile system with four piles, the dynamic stiffness is about four times as large as the single pile between 10 and 20 Hz.
Translational Control in Plasmodium and Toxoplasma Parasites

Science.gov (United States)

Joyce, Bradley R.; Sullivan, William J.; Nussenzweig, Victor

2013-01-01

The life cycles of apicomplexan parasites such as Plasmodium spp. and Toxoplasma gondii are complex, consisting of proliferative and latent stages within multiple hosts. Dramatic transformations take place during the cycles, and they demand precise control of gene expression at all levels, including translation. This review focuses on the mechanisms that regulate translational control in Plasmodium and Toxoplasma, with a particular emphasis on the phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Phosphorylation of eIF2α (eIF2α∼P) is a conserved mechanism that eukaryotic cells use to repress global protein synthesis while enhancing gene-specific translation of a subset of mRNAs. Elevated levels of eIF2α∼P have been observed during latent stages in both Toxoplasma and Plasmodium, indicating that translational control plays a role in maintaining dormancy. Parasite-specific eIF2α kinases and phosphatases are also required for proper developmental transitions and adaptation to cellular stresses encountered during the life cycle. Identification of small-molecule inhibitors of apicomplexan eIF2α kinases may selectively interfere with parasite translational control and lead to the development of new therapies to treat malaria and toxoplasmosis. PMID:23243065
Translational control in Plasmodium and toxoplasma parasites.

Science.gov (United States)

Zhang, Min; Joyce, Bradley R; Sullivan, William J; Nussenzweig, Victor

2013-02-01

The life cycles of apicomplexan parasites such as Plasmodium spp. and Toxoplasma gondii are complex, consisting of proliferative and latent stages within multiple hosts. Dramatic transformations take place during the cycles, and they demand precise control of gene expression at all levels, including translation. This review focuses on the mechanisms that regulate translational control in Plasmodium and Toxoplasma, with a particular emphasis on the phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Phosphorylation of eIF2α (eIF2α∼P) is a conserved mechanism that eukaryotic cells use to repress global protein synthesis while enhancing gene-specific translation of a subset of mRNAs. Elevated levels of eIF2α∼P have been observed during latent stages in both Toxoplasma and Plasmodium, indicating that translational control plays a role in maintaining dormancy. Parasite-specific eIF2α kinases and phosphatases are also required for proper developmental transitions and adaptation to cellular stresses encountered during the life cycle. Identification of small-molecule inhibitors of apicomplexan eIF2α kinases may selectively interfere with parasite translational control and lead to the development of new therapies to treat malaria and toxoplasmosis.
Concentration-dependent, size-independent toxicity of citrate capped AuNPs in Drosophila melanogaster.

Directory of Open Access Journals (Sweden)

Giuseppe Vecchio

Full Text Available The expected potential benefits promised by nanotechnology in various fields have led to a rapid increase of the presence of engineered nanomaterials in a high number of commercial goods. This is generating increasing questions about possible risks for human health and environment, due to the lack of an in-depth assessment of the physical/chemical factors responsible for their toxic effects. In this work, we evaluated the toxicity of monodisperse citrate-capped gold nanoparticles (AuNPs of different sizes (5, 15, 40, and 80 nm in the model organism Drosophila melanogaster, upon ingestion. To properly evaluate and distinguish the possible dose- and/or size-dependent toxicity of the AuNPs, we performed a thorough assessment of their biological effects, using two different dose-metrics. In the first approach, we kept constant the total surface area of the differently sized AuNPs (Total Exposed Surface area approach, TES, while, in the second approach, we used the same number concentration of the four different sizes of AuNPs (Total Number of Nanoparticles approach, TNN. We observed a significant AuNPs-induced toxicity in vivo, namely a strong reduction of Drosophila lifespan and fertility performance, presence of DNA fragmentation, as well as a significant modification in the expression levels of genes involved in stress responses, DNA damage recognition and apoptosis pathway. Interestingly, we found that, within the investigated experimental conditions, the toxic effects in the exposed organisms were directly related to the concentration of the AuNPs administered, irrespective of their size.
Agent independent task planning

Science.gov (United States)

Davis, William S.

1990-01-01

Agent-Independent Planning is a technique that allows the construction of activity plans without regard to the agent that will perform them. Once generated, a plan is then validated and translated into instructions for a particular agent, whether a robot, crewmember, or software-based control system. Because Space Station Freedom (SSF) is planned for orbital operations for approximately thirty years, it will almost certainly experience numerous enhancements and upgrades, including upgrades in robotic manipulators. Agent-Independent Planning provides the capability to construct plans for SSF operations, independent of specific robotic systems, by combining techniques of object oriented modeling, nonlinear planning and temporal logic. Since a plan is validated using the physical and functional models of a particular agent, new robotic systems can be developed and integrated with existing operations in a robust manner. This technique also provides the capability to generate plans for crewmembers with varying skill levels, and later apply these same plans to more sophisticated robotic manipulators made available by evolutions in technology.
A community translational research pilot grants program to facilitate community--academic partnerships: lessons from Colorado's clinical translational science awards.

Science.gov (United States)

Main, Deborah S; Felzien, Maret C; Magid, David J; Calonge, B Ned; O'Brien, Ruth A; Kempe, Allison; Nearing, Kathryn

2012-01-01

National growth in translational research has increased the need for practical tools to improve how academic institutions engage communities in research. One used by the Colorado Clinical and Translational Sciences Institute (CCTSI) to target investments in community-based translational research on health disparities is a Community Engagement (CE) Pilot Grants program. Innovative in design, the program accepts proposals from either community or academic applicants, requires that at least half of requested grant funds go to the community partner, and offers two funding tracks: One to develop new community-academic partnerships (up to $10,000), the other to strengthen existing partnerships through community translational research projects (up to $30,000). We have seen early success in both traditional and capacity building metrics: the initial investment of $272,742 in our first cycle led to over $2.8 million dollars in additional grant funding, with grantees reporting strengthening capacity of their community- academic partnerships and the rigor and relevance of their research.
Radioactive airborne effluents and the environmental impact assessment of CAP1400 nuclear power plant under normal operation

Energy Technology Data Exchange (ETDEWEB)

Zhang, Qiong; Guo, RuiPing; Zhang, ChunMing; Chen, XiaoQiu; Wang, Bo, E-mail: wangbo@chinansc.cn

2014-12-15

Highlights: • Typical radionuclides dispersion from CAP1400 under normal operation was simulated. • Modified Gaussian model considered radioactive decay, dry and wet deposition and so on. • The radioactive impact pathways on the public through atmosphere were compared. • The maximum individual effective dose was lower than the public irradiation limit. - Abstract: China Advanced Passive nuclear power plant with installed capacity reaching to 1400 MW (CAP1400) is independently designed as the China's state-of-the-art third generation nuclear power brand based on AP1000 technology digestion and absorption. The concentration of typical radionuclides dispersed from CAP1400 under normal operation was calculated with modified Gaussian model, considering mixed layer height, dry deposition, wet deposition, radioactive decay and so on. The atmospheric dispersion factors, ground deposition rate, individual dose and public dose were also investigated to estimate the radioactive effects of CAP1400 under normal operation on surrounding environment and human beings. The radioactive impact pathways on the public through atmosphere, such as immersion irradiation in the smoke plume, internal irradiation from ingestion and inhalation and external irradiation from surface deposition were briefly introduced with focus on the comparison of the maximum individual effective dose to different group from atmospheric dispersion. All computation results show that the maximum individual irradiation dose happened to children with total effective irradiation dose of 4.52E−03 mSv/y, which was lower than the public irradiation limit of 0.25 mSv/y.
Radioactive airborne effluents and the environmental impact assessment of CAP1400 nuclear power plant under normal operation

International Nuclear Information System (INIS)

Zhang, Qiong; Guo, RuiPing; Zhang, ChunMing; Chen, XiaoQiu; Wang, Bo

2014-01-01

Highlights: • Typical radionuclides dispersion from CAP1400 under normal operation was simulated. • Modified Gaussian model considered radioactive decay, dry and wet deposition and so on. • The radioactive impact pathways on the public through atmosphere were compared. • The maximum individual effective dose was lower than the public irradiation limit. - Abstract: China Advanced Passive nuclear power plant with installed capacity reaching to 1400 MW (CAP1400) is independently designed as the China's state-of-the-art third generation nuclear power brand based on AP1000 technology digestion and absorption. The concentration of typical radionuclides dispersed from CAP1400 under normal operation was calculated with modified Gaussian model, considering mixed layer height, dry deposition, wet deposition, radioactive decay and so on. The atmospheric dispersion factors, ground deposition rate, individual dose and public dose were also investigated to estimate the radioactive effects of CAP1400 under normal operation on surrounding environment and human beings. The radioactive impact pathways on the public through atmosphere, such as immersion irradiation in the smoke plume, internal irradiation from ingestion and inhalation and external irradiation from surface deposition were briefly introduced with focus on the comparison of the maximum individual effective dose to different group from atmospheric dispersion. All computation results show that the maximum individual irradiation dose happened to children with total effective irradiation dose of 4.52E−03 mSv/y, which was lower than the public irradiation limit of 0.25 mSv/y
Africa Centre for Systematic Reviews and Knowledge Translation ...

International Development Research Centre (IDRC) Digital Library (Canada)

Several initiatives focused on bridging the "know-do" gap emphasize ... and knowledge translation to bridge the gaps between research and health policy. ... International Water Resources Association, in close collaboration with IDRC, ...
Effective knowledge management in translational medicine.

Science.gov (United States)

Szalma, Sándor; Koka, Venkata; Khasanova, Tatiana; Perakslis, Eric D

2010-07-19

The growing consensus that most valuable data source for biomedical discoveries is derived from human samples is clearly reflected in the growing number of translational medicine and translational sciences departments across pharma as well as academic and government supported initiatives such as Clinical and Translational Science Awards (CTSA) in the US and the Seventh Framework Programme (FP7) of EU with emphasis on translating research for human health. The pharmaceutical companies of Johnson and Johnson have established translational and biomarker departments and implemented an effective knowledge management framework including building a data warehouse and the associated data mining applications. The implemented resource is built from open source systems such as i2b2 and GenePattern. The system has been deployed across multiple therapeutic areas within the pharmaceutical companies of Johnson and Johnsons and being used actively to integrate and mine internal and public data to support drug discovery and development decisions such as indication selection and trial design in a translational medicine setting. Our results show that the established system allows scientist to quickly re-validate hypotheses or generate new ones with the use of an intuitive graphical interface. The implemented resource can serve as the basis of precompetitive sharing and mining of studies involving samples from human subjects thus enhancing our understanding of human biology and pathophysiology and ultimately leading to more effective treatment of diseases which represent unmet medical needs.
Internal field probing of translating FRCs

International Nuclear Information System (INIS)

Armstrong, W.T.; Chrien, R.E.; Milroy, R.D.

1984-11-01

Magnetic field probes have been employed to study the internal field structure of Field-Reversed Configurations (FRCs) translating past the probes in the FRX-C/T device. Internal closed flux surfaces can be studied in this manner with minimal perturbation because of the rapid transit of the plasma (translation velocity v/sub z/ approx. 10 cm/μs). Data have been taken using a 5-mtorr-D 2 gas-puff mode of operation in the FRC source coil which yields an initial plasma density of approx. 1 x 10 15 cm -3 and x/sub s/ approx. 0.40. FRCs translate from the approx. 25 cm radius source coil into a 20 cm radius metal translation vessel. Of many translation conditions studied, the condition considered here is translation into a weak guide field resulting in expansion of the FRC to conditions of density approx. 3 x 10 14 and x/sub s/ approx. 0.7. The expected reversed B/sub z/ structure is observed. Evidence of island structure is also observed. Fluctuating levels of B/sub THETA/ are observed with amplitudes less than or equal to B 0 /3 and values of flux approx. 4 x the poloidal flux. Values of β on the separatrix of β/sub s/ approx. = 0.3 (indexed to the external field) are implied from the field measurements. This decrease of β/sub s/ with increased x/sub s/ is expected, and desirable for improved plasma confinement
Effective knowledge management in translational medicine

Directory of Open Access Journals (Sweden)

Khasanova Tatiana

2010-07-01

Full Text Available Abstract Background The growing consensus that most valuable data source for biomedical discoveries is derived from human samples is clearly reflected in the growing number of translational medicine and translational sciences departments across pharma as well as academic and government supported initiatives such as Clinical and Translational Science Awards (CTSA in the US and the Seventh Framework Programme (FP7 of EU with emphasis on translating research for human health. Methods The pharmaceutical companies of Johnson and Johnson have established translational and biomarker departments and implemented an effective knowledge management framework including building a data warehouse and the associated data mining applications. The implemented resource is built from open source systems such as i2b2 and GenePattern. Results The system has been deployed across multiple therapeutic areas within the pharmaceutical companies of Johnson and Johnsons and being used actively to integrate and mine internal and public data to support drug discovery and development decisions such as indication selection and trial design in a translational medicine setting. Our results show that the established system allows scientist to quickly re-validate hypotheses or generate new ones with the use of an intuitive graphical interface. Conclusions The implemented resource can serve as the basis of precompetitive sharing and mining of studies involving samples from human subjects thus enhancing our understanding of human biology and pathophysiology and ultimately leading to more effective treatment of diseases which represent unmet medical needs.
T box riboswitches in Actinobacteria: Translational regulation via novel tRNA interactions

Science.gov (United States)

Sherwood, Anna V.; Grundy, Frank J.; Henkin, Tina M.

2015-01-01

The T box riboswitch regulates many amino acid-related genes in Gram-positive bacteria. T box riboswitch-mediated gene regulation was shown previously to occur at the level of transcription attenuation via structural rearrangements in the 5′ untranslated (leader) region of the mRNA in response to binding of a specific uncharged tRNA. In this study, a novel group of isoleucyl-tRNA synthetase gene (ileS) T box leader sequences found in organisms of the phylum Actinobacteria was investigated. The Stem I domains of these RNAs lack several highly conserved elements that are essential for interaction with the tRNA ligand in other T box RNAs. Many of these RNAs were predicted to regulate gene expression at the level of translation initiation through tRNA-dependent stabilization of a helix that sequesters a sequence complementary to the Shine–Dalgarno (SD) sequence, thus freeing the SD sequence for ribosome binding and translation initiation. We demonstrated specific binding to the cognate tRNAIle and tRNAIle-dependent structural rearrangements consistent with regulation at the level of translation initiation, providing the first biochemical demonstration, to our knowledge, of translational regulation in a T box riboswitch. PMID:25583497
Neutron transition multipole moment for /sup 88/Sr(. cap alpha. ,. cap alpha. ')/sup 88/Sr (2/sup +/, 1. 84 MeV)

Energy Technology Data Exchange (ETDEWEB)

Datta, S.K.; Ray, S.; Majumdar, H.; Ghosh, S.K.; Samanta, C.; Dasgupta, P.; Chintalapudi, S.N.; Banerjee, S.R.

1989-04-01

The neutron transition multipole moment, M/sub n/, for (0/sup +/..-->..2/sup +/, 1.84 MeV) transition is inferred by measuring the (..cap alpha..,..cap alpha..') angular distribution at E/sub ..cap alpha../ = 50 MeV and comparing it with a microscopic distorted-wave Born approximation calculation. Proton transition densities are taken from electron scattering data. M/sub n//M/sub p/ is found to be substantially less than N/Z in agreement with the (p,p') result.
MANAGING THE TRANSLATION OF ECONOMIC TEXTS

Directory of Open Access Journals (Sweden)

Pop Anamaria Mirabela

2012-12-01

Full Text Available Theoretically, translation may pass as science; practically, it seems closer to art. Translation is a challenging activity requiring a set of abilities and posing few difficulties that appear during the translation process. This paper investigates the extent to which sub-technical vocabulary can constitute a problem to Romanian students of economics reading in English, by looking at the translations produced as independent or pair work during English classes and analyzing the various errors which may appeared. The exigencies required by the efficient business communication have increased in the past few decades because of rising international trade, increased migration, globalization, the recognition of linguistic minorities, and the expansion of the mass media and technology. All these led us to approach the topic of translation which is actually a job that requires skills, stages of research necessary for disclosure of transfer characteristic into the target language, training, experience and a good sense of languages. The paper defines the theoretical issues and terminology: translation, types of translation, economic texts and then focuses on the presentation of the practical work carried out throughout the academic year of second year students. Considering that only 28% of the entire European population can read English, and even less people in South America and Asia can, it is obvious that an effective communication of business matters relies on an accurate understanding of terminology. Economics is a field of knowledge in accelerated scientific and technological development. As there is a permanent and ever increasing need to quickly update their knowledge, economists read and learn directly in the original language of the publication and stick to it in daily usage, including conferences, scientific events and articles written in Romanian. Besides researching properly the markets, finding distribution channels, and dealing with legal
Cap Bubble Drift Velocity in a Confined Test Section

International Nuclear Information System (INIS)

Xiaodong Sun; Seungjin Kim; Mamoru Ishii; Lincoln, Frank W.; Beus, Stephen G.

2002-01-01

In the two-group interfacial area transport equation, bubbles are categorized into two groups, i.e., spherical/distorted bubbles as group 1 and cap/slug/churn-turbulent bubbles as group 2. The bubble rise velocities for both groups of bubbles may be estimated by the drift flux model by applying different distribution parameters and drift velocities for both groups. However, the drift velocity for group 2 bubbles is not always applicable (when the wall effect becomes important) as in the current test loop of interest where the flow channel is confined by two parallel flat walls, with a dimension of 200-mm in width and 10-mm in gap. The previous experiments indicated that no stable slug flow existed in this test section, which was designed to permit visualization of the flow patterns and bubble characteristics without the distortion associated with curved surfaces. In fact, distorted cap bubbly and churn-turbulent flow was observed. Therefore, it is essential to developed a correlation for cap bubble drift velocity in this confined flow channel. Since the rise velocity of a cap bubble depends on its size, a high-speed movie camera is used to capture images of cap bubbles to obtain the bubble size information. Meanwhile, the rise velocity of cap and elongated bubbles (called cap bubbles hereafter) is investigated by examining the captured images frame by frame. As a result, the conventional correlation of drift velocity for slug bubbles is modified and acceptable agreements between the measurements and correlation estimation are achieved
Report of Committee for JAEA Internationalization Initiative (Translated document)

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-07-15

In global circumstances surrounding nuclear energy, the role expected by the Japan Atomic Energy Agency (JAEA) is becoming increasingly important. JAEA has promoted an initiative for an international hub in order to increase the scientific competitiveness of Japan and make international contributions, by gathering excellent researchers from the entire world with the latest facilities. Also, JAEA has established the 'Committee for JAEA Internationalization Initiative', which will discuss issues such as environmental improvement for accepted foreigners, direction of efforts for internationalization initiative and strategies to improve the current situation. This report mentions the results of the committee's discussion including current issues for the initiative and recommendations for their solution, as well as issues to be discussed in order to enhance international awareness of JAEA staff. The following is the summary of the recommendations for the initiative: Set up local teams that focus on the situation of each site in order to provide detailed support for foreigners from diversified backgrounds. Develop systems for emergency situations to provide information for safety swiftly for foreigners and confirm their safety, in addition to preparing emergency goods. Prepare bilingual documents and systems that foreigners need to use for their work based on importance and frequency of use of such systems and documents. (author)

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